Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk

PubMed Central

Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

2015-01-01

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease. PMID:26057532

Scabies presenting with bullous pemphigoid-like lesions.

PubMed

Ansarin, Habib; Jalali, Mir Hadi Aziz; Mazloomi, Shadi; Soltani-Arabshahi, Razieh; Setarehshenas, Roya

2006-01-27

A wide range of clinical manifestations may be seen in scabies, from classic pruritic papules and burrows to secondary features such as impetigo. Bullus lesions are a less frequent. Twenty cases of scabies presenting with bullae have been reported so far in the medical literature. Differentiating this subtype of scabies from the immunobullous disease bullus pemphigoid is a diagnostic challenge. A 42-year-old man was referred to our dermatology outpatient clinic with 3-month history of severe pruritus and tense blisters affecting mainly the lower trunk, arms and legs. An initial biopsy was suggestive for bullous pemphigoid. Close physical examination revealed small excoriated papules and a few burrows on borders of the hands and wrists. Skin scraping of the lesions on wrists was positive for Sarcoptes scabiei. Another biopsy specimen from a recent blister revealed subepidermal bullae with fibrin and inflammatory cells, particularly eosinophils. Direct immunofluorescence exam was negative. The patient was treated with lindane lotion followed by crotamiton cream with near complete resolution of the lesions. Scabies must be considered in patients presenting with recent onset of unexplained pruritic bullous lesions. Biopsy and immunofluorescence studies together with skin scrapings for Sarcoptes scabiei could help to differentiate these cases from bullous pemphigoid. Antiscabietic treatment results in resolution of bullous lesions in the affected patients.

Scabies masquerading as bullous pemphigoid: scabies surrepticius

PubMed Central

Cohen, Philip R

2017-01-01

Scabies, a parasitic infestation caused by the mite Sarcoptes scabiei, is diagnosed by observing either the mite, its ova, or its excrement. The mite tracts, known as burrows and a characteristic presentation of the pruritic condition, are typically found on the web spaces between the fingers. Other cutaneous lesions include excoriated papules, pustules, and vesicles. However, atypical clinical variants of scabies, such as bullous, crusted, hidden, incognito, nodular, and scalp forms of the parasitic infestation, mimic the morphologic features of other non-parasitic dermatoses. A 76-year-old man presented with pruritic blisters and urticarial plaques that demonstrated not only pathology changes, but direct immunofluorescence also showed findings of bullous pemphigoid. His condition improved, but did not resolve, with topical corticosteroid cream for the management of the primary autoimmune blistering disorder. When other family members subsequently developed scabies, the correct diagnosis for his condition, bullous scabies, was established by demonstrating mites, ova, and scybala on a mineral oil preparation from a skin scraping of a newly appearing burrow. Bullous scabies can masquerade not only clinically, but also both pathologically and immunologically as bullous pemphigoid. Scabies serrupticius is introduced as a unifying term to designate all of the non-classic presentations of S. scabiei mite infestation. PMID:28883737

Cytokines and bullous pemphigoid.

PubMed

D'Auria, L; Cordiali Fei, P; Ameglio, F

1999-06-01

This report reviews the data presented in the literature concerning the presence and levels of different cytokines in sera, lesional tissue or blister fluids of patients with bullous pemphigoid. The list of cytokines analysed includes 21 molecules: interleukins (IL)-1 => 8, IL-10 => 13, IL-15, granulocyte-monocyte-colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), oncostatin-M (OSM), regulated upon activation normal T cell expressed and presumably secreted (RANTES), transforming growth factor-beta 1 (TGF-beta 1), tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF). Basic information regarding the functions of these cytokines and their possible involvement in the pathogenetic steps of the disease, such as autoantigen expression, autoantibody induction, complement activation, local cell recruitment and stimulation, resident cell activation, release of various effector molecules and tissue damage are also reported. A specific function for each cytokine in bullous pemphigoid induction cannot be still defined, however, the literature attributes a major role to IL-1, IL-4, IL-5, IL-6, IL-8 and IFN-gamma. On the basis of significant (direct or inverse) correlations found between disease intensity and the blister fluid/serum levels, the following cytokines IL-7, IL-15, RANTES, VEGF and TNF-alpha, besides those previously mentioned, may also be involved in this disease.

Narrowband UVB-induced lichen planus pemphigoide

PubMed Central

Mandy Chan, Wai Man; See Lee, Joyce Siong; Thiam Theng, Colin Seng; Chua, Sze Hon; Boon Oon, Hazel Hwee

2011-01-01

Lichen planus pemphigoides (LPP) is an autoimmune disease characterised by evolution of subepidermal blisters on normal and lichen planus affected skin. We describe a case of LPP in a 54-year-old Chinese woman. The patient presented with psoriasiform plaques and was diagnosed with guttate psoriasis. Narrowband ultraviolet B (NBUVB) therapy was commenced, and she experienced a generalised eruption of violaceous papules, bullae over the lower limbs, and Wickham's striae over the buccal mucosa. Histology from a plaque revealed interface dermatitis, while a specimen from a blister showed subepidermal bulla. Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane. A diagnosis of LPP was made on clinicopathological grounds. This is the first case report of NBUVB alone in unmasking LPP. In this case report, we describe the pathological mechanism of NBUVB in the development of LPP and key features distinguishing LPP from bullous lupus erythematosus, bullous lichen planus, bullous pemphigoid, and psoriasis. PMID:25386295

Role of Progesterone Receptor Isoforms in Regulation of Cell Adhesion and Apoptosis

DTIC Science & Technology

2002-06-01

repeatable) (figure 1 below). We used taxol to induce apoptosis instead of tumor necrosis factor (TNF) (as initially proposed in the grant) because...highlighted in red in Fig. 6A), monocyte chemotactic protein (MCP; open arrow in Fig. 6A and isolated in Fig. 6B, top) and bullous pemphigoid antigen...red. The open arrow indicates monocyte chemotactic protein (MCP) and closed arrow indi- cates bullous pemphigoid antigen (BPAG). B, top, isolated

Expression of Selected Integrins and Selectins in Bullous Pemphigoid

PubMed Central

Żebrowska, Agnieszka; Sysa-Jędrzejowska, Anna; Wągrowska-Danilewicz, Małgorzata; Joss-Wichman, Ewa; Erkiert-Polguj, Anna; Waszczykowska, Elżbieta

2007-01-01

Blister development in bullous pemphigoid (BP) results from destruction of hemidesmosomes and basement membrane components within the dermoepidermal junction by autoantibodies. Adhesion molecules can take part in pathogenesis of this disease. The aim of the study was to determine the localization and expression of L- and E-selectins and β1, β3, and β4 integrins by immunohistochemistry in skin lesions of 21 patients with BP, compared with 10 healthy subjects. Expression of L and E selectins and β1, β3 integrins was detected mainly in basal keratinocytes and in inflammatory infiltrates in the dermis, expression of β4 integrin was irregular and was detected mainly in dermal part of the blister, while in the control group only weak and single expression of the examined molecules was detected in basal keratinocytes and endothelium cells. The obtained results reveal the important role of selected selectins and integrins in development of skin lesions in BP. PMID:17515951

Photodynamic therapy effective for the treatment of actinic keratosis and basal cell carcinoma in bullous pemphigoid patients.

PubMed

Canavan, Theresa N; de la Feld, Salma Faghri; Huang, Conway; Sami, Naveed

2017-06-01

Treating skin cancers and extensive actinic keratosis in patients with bullous pemphigoid (BP) can be challenging. Treatment options pose unique risks in these patients as surgical wounds can have delayed wound healing and photodynamic therapy (PDT) may exacerbate their blistering disease. We report the successful use of PDT to treat actinic keratosis and skin cancers in two patients with BP, both of whom had excellent response to PDT and tolerated treatment without any bullous disease flares. Carefully selected patients with skin cancers and stable, well controlled BP can be safely considered for treatment using PDT. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of an ELISA for sensitive and specific detection of IgA autoantibodies against BP180 in pemphigoid diseases

PubMed Central

2011-01-01

Background Pemphigoids are rare diseases associated with IgG, IgE and IgA autoantibodies against collagen XVII/BP180. An entity of the pemphigoid group is the lamina lucida-type of linear IgA disease (IgA pemphigoid) characterized by IgA autoantibodies against BP180. While for the detection of IgG and IgE autoantibodies specific to collagen XVII several ELISA systems have been established, no quantitative immunoassay has been yet developed for IgA autoantibodies. Therefore, the aim of the present study was to develop an ELISA to detect IgA autoantibodies against collagen XVII in the sera of patients with pemphigoids. Methods We expressed a soluble recombinant form of the collagen XVII ectodomain in mammalian cells. Reactivity of IgA autoantibodies from patients with IgA pemphigoid was assessed by immunofluorescence microscopy and immunoblot analysis. ELISA test conditions were determined by chessboard titration experiments. The sensitivity, specificity and the cut-off were determined by receiver-operating characteristics analysis. Results The optimized assay was carried out using sera from patients with IgA pemphigoid (n = 30) and healthy donors (n = 105). By receiver operating characteristics (ROC) analysis, an area under the curve of 0.993 was calculated, indicating an excellent discriminatory capacity. Thus, a sensitivity and specificity of 83.3% and 100%, respectively, was determined for a cut-off point of 0.48. As additional control groups, sera from patients with bullous pemphigoid (n = 31) and dermatitis herpetiformis (n = 50), a disease associated with IgA autoantibodies against epidermal transglutaminase, were tested. In 26% of bullous pemphigoid patients, IgA autoantibodies recognized the ectodomain of collagen XVII. One of 50 (2%) of dermatitis herpetiformis patients sera slightly topped the cut-off value. Conclusions We developed the first ELISA for the specific and sensitive detection of serum IgA autoantibodies specific to collagen XVII in patients with pemphigoids. This immunoassay should prove a useful tool for clinical and translational research and should essentially improve the diagnosis and disease monitoring of patients with IgA pemphigoid. Moreover, our findings strongly suggest that IgA pemphigoid and IgG bullous pemphigoid represent two ends of the clinical spectrum of an immunological loss of tolerance against components of hemidesmosomes, which is mediated by both IgG and IgA autoantibodies. PMID:21619684

Bullous pemphigoid followed by pustular psoriasis showing Th1, Th2, Treg and Th17 immunological changes.

PubMed

Yasukawa, Shinsuke; Dainichi, Teruki; Kokuba, Hisashi; Moroi, Yoichi; Urabe, Kazunori; Hashimoto, Takashi; Furue, Masutaka

2009-01-01

Psoriasis vulgaris is occasionally accompanied by autoimmune bullous diseases, but the opposite is very rare. We document here the first reported case of generalized pustular psoriasis that appeared during steroid therapy for bullous pemphigoid. The serum cytokine levels and the results of an immunohistochemical study over the disease course suggest that the immunological state was consistent with a shift from Th2-dominance to Th1-dominance. IL-17-producing cells appeared in the skin lesions when each disease was most exacerbated and disappeared after remission. Thus, the present case demonstrated a dynamic immunological state in which the appearances of Th1 and Th2 as well as Th17 varied during the course of the disease.

Bullous scabies: a case report and review of the literature.

PubMed

Maan, Muhammad Arslan Arif; Maan, Muhammad Soban Arif; Sohail, Abdul Malik Amir Humza; Arif, Muhammad

2015-06-20

Scabies is a common parasitic infection caused by the mite Sarcoptes Scabiei. About 300 million cases of scabies are reported annually. Scabies usually presents clinically with an erythematous excoriated papulovesicular rash, burrows, nodules and hyperkeratotic lesions in specific body areas. A rare presentation of scabies is the bullous pemphigoid-like bullous scabies. So far, to the best of our knowledge, only 32 cases of bullous scabies have been reported in medical literature, of which only 11 were under 60 years of age at the time of initial presentation. This is the first case of bullous scabies being reported from Pakistan. Herein we discuss, with reference to the existing literature, the case of a 23-year-old Punjabi male who presented with a 3 day history of a tense, non-erythematous, non-tender bulla measuring approximately 0.5 cm x 0.8 cm on the right foot near the interdigital cleft. He was diagnosed to have bullous scabies. The diagnosis of scabies should be considered in all patients who present with tense bullous lesions accompanied by pruritus and a maculopapular rash. This is particularly relevant if these lesions do not resolve with steroid treatment. In such patients, in order to prevent a misdiagnosis of bullous pemphigoid, scrapings for Sarcoptes Scabiei mites and eggs should be taken.

Autoimmune bullous skin diseases. Part 1: Clinical manifestations.

PubMed

Kneisel, Andrea; Hertl, Michael

2011-10-01

Autoimmune bullous skin diseases are characterized by autoantibodies against adhesion molecules of the skin. Pemphigus is a disorder with an intraepidermal loss of adhesion and is characterized by fragile blisters and erosions. Pemphigus vulgaris often shows extensive lesions of the oral mucosa, while pemphigus foliaceus is commonly restricted to cutaneous involvement with puff pastry-like scale formation. Paraneoplastic pemphigus is obligatorily associated with malignancies and often presents as hemorrhagic stomatitis with multiforme-like exanthems. IgA pemphigus typically presents with pustules and annular plaques but not with mucosal involvement. The clinical spectrum of the pemphigoids includes tense blisters, urticarial plaques, and prurigo- like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a "cluster of jewels"-like pattern in childhood and is more heterogeneous in adulthood. Classical epidermolysis bullosa acquisita shows extensive skin fragility. Dermatitis herpetiformis is associated with gluten-sensitive enteropathy and manifests clinically with severe itching and papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The intention of the review is to demonstrate the heterogeneous clinical spectrum of autoimmune bullous disorders. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

Squamous cell carcinoma of penis with bullous pemphigoid masquerading as lymphogranuloma venereum

PubMed Central

Venugopal, V.; Gnanaraj, Pushpa; Fernandes, S. D.; Narasimhan, Murali; Karthikeyan, Subashini; Rahul, Shwetha

2013-01-01

We report a case of a 60-year old unmarried male who presented with multiple ulcers and foul smelling discharge from the groin since 4 months and multiple tense bullae over the trunk of 1 month duration. Groove sign was present. Investigations for lymphogranuloma venereum (LGV) and other sexually transmitted diseases were negative. Histopathology from the ulcer in the groin and growth in the penis revealed squamous cell carcinoma (SCC). Skin biopsy of bulla was diagnostic of bullous pemphigoid (BP). We report a rare case of SCC masquerading as LGV with BP occurring as a paraneoplastic phenomenon. PMID:23919055

Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseases.

PubMed

Matsushita, Takashi; Hasegawa, Minoru; Matsushita, Yukiyo; Echigo, Takeshi; Wayaku, Takamasa; Horikawa, Mayuka; Ogawa, Fumihide; Takehara, Kazuhiko; Sato, Shinichi

2007-02-01

Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma.

[Cicatricial pemphigoid, mucous membrane pemphigoid].

PubMed

Doffoel-Hantz, Valérie; Robert, Pierre-Yves; Bédane, Christophe

2010-10-01

Mucous membrane pemphigoid belongs to the family of sub-epidermal bullous diseases and is clinically characterized by mucosal involvement leading to fibrosis and scarring. Cutaneous involvement is unfrequent and oral mucosa and conjunctivas are the most frequently involves mucosa. Treatment relies on anti-inflammatory and immunosuppressive drugs. The main goal is the limitation of the fibrosing potential of the autoimmune deposits within various mucous membranes. Copyright © 2010. Published by Elsevier Masson SAS.

Expression of the JAK/STAT Signaling Pathway in Bullous Pemphigoid and Dermatitis Herpetiformis

PubMed Central

Wozniacka, A.; Waszczykowska, E.; Zebrowska, A.

2017-01-01

A family of eleven proteins comprises the Janus kinases (JAK) and signal transducers and activators of transcription (STAT) signaling pathway, which enables transduction of signal from cytokine receptor to the nucleus and activation of transcription of target genes. Irregular functioning of the cascade may contribute to pathogenesis of autoimmune diseases; however, there are no reports concerning autoimmune bullous diseases yet to be published. The aim of this study was to evaluate the expression of proteins constituting the JAK/STAT signaling pathway in skin lesions and perilesional area in dermatitis herpetiformis (DH) and bullous pemphigoid (BP), as well as in the control group. Skin biopsies were collected from 21 DH patients, from 20 BP patients, and from 10 healthy volunteers. The localization and expression of selected STAT and JAK proteins were examined by immunohistochemistry and immunoblotting. We found significantly higher expression of JAK/STAT proteins in skin lesions in patients with BP and DH, in comparison to perilesional skin and the control group, which may be related to proinflammatory cytokine network and induction of inflammatory infiltrate in tissues. Our findings suggest that differences in the JAK and STAT expression may be related to distinct cytokines activating them and mediating neutrophilic and/or eosinophilic infiltrate. PMID:29203970

IL-17 Expression in Dermatitis Herpetiformis and Bullous Pemphigoid

PubMed Central

Wagrowska-Danilewicz, Malgorzata; Stasikowska-Kanicka, Olga; Cynkier, Anna; Sysa-Jedrzejowska, Anna; Waszczykowska, Elzbieta

2013-01-01

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although cytokines are critical for the inflammatory process, there are single findings concerning concentration of IL-17 in bullous diseases. The goal of this study was to assess IL-17 expression in DH and BP patients. Skin biopsies were taken from 10 DH, 14 BP patients and from 10 healthy subjects. The localization and expression of IL-17 was studied by immunohistochemistry and the serum concentration was measured by immunoassays. Expression of IL-17 in the epidermis and in influxed cells in dermis was detected in skin biopsies. Expression of IL-17 was statistically higher in epidermis and infiltration cells in specimens from BP than from DH patients. Examined interleukin expression was detected in perilesional skin of all patients but it was much lower than in lesional skin. The expression of IL-17 was not observed in biopsies from healthy people. Serum level of IL-17 was statistically higher in BP and DH groups as compared to control group. Our results provide the evidence that IL-17 may play an essential role in activating and recruiting eosinophils and neutrophils, which ultimately contribute to the tissue damage in DH and BP. PMID:23970818

Epidermolysis Bullosa Acquitsita

PubMed Central

Gupta, Rishu; Woodley, David T.; Chen, Mei

2011-01-01

EBA is a rare, acquired, chronic subepidermal bullous disease of the skin and mucosa characterized by autoantibodies to type VII collagen structures, a major component of anchoring fibrils, that attach the epidermis onto the dermis. EBA patients have tissue-bound as well as circulating anti-type VII collagen autoantibodies that attack type VII collagen and result in a reduction or perturbation of normally functioning anchoring fibrils. Patients with EBA have skin fragility, blisters, erosions, scars, milia, and nail loss: all features reminiscent of genetic dystrophic epidermolysis bullosa. These anti-type VII collagen antibodies are “pathogenic” because when injected into mice, the mice develop an EBA-like blistering disease. In addition to the classical mechanobullous presentation, EBA also has several other distinct clinical syndromes similar to bullous pemphigoid, Brunsting-Perry pemphigoid, or cicatricial pemphigoid. Although treatment for EBA is often unsatisfactory, some therapeutic success has been achieved with colchicine, dapsone, plasmaphoresis, photopheresis, infliximab, and intravenous immunoglobulin. PMID:22137228

Mediators of mast cells in bullous pemphigoid and dermatitis herpetiformis.

PubMed

Zebrowska, Agnieszka; Wagrowska-Danilewicz, Malgorzata; Danilewicz, Marian; Stasikowska-Kanicka, Olga; Kulczycka-Siennicka, Lilianna; Wozniacka, Anna; Waszczykowska, Elzbieta

2014-01-01

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are skin diseases associated with inflammation. However, few findings exist concerning the role of mast cells in autoimmune blistering disease. Skin biopsies were taken from 27 BP and 14 DH patients, as well as 20 healthy individuals. Immunohistochemistry was used to identify the localization and mast cell expression of TNFα and MMP9 in skin lesions and perilesional skin. The serum concentrations of TNFα, MMP9, chymase, tryptase, PAF, and IL-4 were measured by immunoassay. TNFα and MMP9 expression in the epidermis and in inflammatory influxed cells in the dermis was detected in skin biopsies from patients. Although these mediators were found to be expressed in the perilesional skin of all patients, the level was much lower than that in lesional skin. Increased serum PAF levels were observed in BP patients. Mast cells may play an essential role in activating inflammation, which ultimately contributes to the tissue damage observed in BP and DH. Our findings suggest that differences in the pattern of cytokine expression directly contribute to variations in cellular infiltration in DH and BP.

Mediators of Mast Cells in Bullous Pemphigoid and Dermatitis Herpetiformis

PubMed Central

Stasikowska-Kanicka, Olga; Kulczycka-Siennicka, Lilianna; Wozniacka, Anna; Waszczykowska, Elzbieta

2014-01-01

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are skin diseases associated with inflammation. However, few findings exist concerning the role of mast cells in autoimmune blistering disease. Skin biopsies were taken from 27 BP and 14 DH patients, as well as 20 healthy individuals. Immunohistochemistry was used to identify the localization and mast cell expression of TNFα and MMP9 in skin lesions and perilesional skin. The serum concentrations of TNFα, MMP9, chymase, tryptase, PAF, and IL-4 were measured by immunoassay. TNFα and MMP9 expression in the epidermis and in inflammatory influxed cells in the dermis was detected in skin biopsies from patients. Although these mediators were found to be expressed in the perilesional skin of all patients, the level was much lower than that in lesional skin. Increased serum PAF levels were observed in BP patients. Mast cells may play an essential role in activating inflammation, which ultimately contributes to the tissue damage observed in BP and DH. Our findings suggest that differences in the pattern of cytokine expression directly contribute to variations in cellular infiltration in DH and BP. PMID:25400334

B-cell activating factor detected on both naïve and memory B cells in bullous pemphigoid.

PubMed

Qian, Hua; Kusuhara, Masahiro; Li, Xiaoguang; Tsuruta, Daisuke; Tsuchisaka, Atsunari; Ishii, Norito; Koga, Hiroshi; Hayakawa, Taihei; Ohara, Koji; Karashima, Tadashi; Ohyama, Bungo; Ohata, Chika; Furumura, Minao; Hashimoto, Takashi

2014-08-01

B-cell activating factor (BAFF), an important immune regulatory cytokine, is involved in development of autoimmune diseases. Although BAFF is expressed in various cells, including dendritic cells (DCs) and monocytes, BAFF expression on B cells has not been well documented. In the present study, BAFF molecules on DCs and naïve and memory B cells in autoimmune bullous diseases, including pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid (BP), were analysed by flow cytometry. Compared with healthy controls (HC), BAFF expression on naïve and memory B cells increased significantly in BP. No difference in BAFF receptor expression in naïve and memory B cells was shown among all study groups. Furthermore, BAFF expression in both naïve and memory B cells of BP, but not HC, was detected by confocal microscopic analysis. These results implied that BAFF expressed by B cells may play a pathogenic role in autoimmune bullous diseases, particularly BP. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Role of different pathways of the complement cascade in experimental bullous pemphigoid

PubMed Central

Nelson, Kelly C.; Zhao, Minglang; Schroeder, Pamela R.; Li, Ning; Wetsel, Rick A.; Diaz, Luis A.; Liu, Zhi

2006-01-01

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease associated with autoantibodies directed against the hemidesmosomal proteins BP180 and BP230 and inflammation. Passive transfer of antibodies to the murine BP180 (mBP180) induces a skin disease that closely resembles human BP. In the present study, we defined the roles of the different complement activation pathways in this model system. Mice deficient in the alternative pathway component factor B (Fb) and injected with pathogenic anti-mBP180 IgG developed delayed and less intense subepidermal blisters. Mice deficient in the classical pathway component complement component 4 (C4) and WT mice pretreated with neutralizing antibody against the first component of the classical pathway, C1q, were resistant to experimental BP. These mice exhibited a significantly reduced level of mast cell degranulation and polymorphonuclear neutrophil (PMN) infiltration in the skin. Intradermal administration of compound 48/80, a mast cell degranulating agent, restored BP disease in C4–/– mice. Furthermore, C4–/– mice became susceptible to experimental BP after local injection of PMN chemoattractant IL-8 or local reconstitution with PMNs. These findings provide the first direct evidence to our knowledge that complement activation via the classical and alternative pathways is crucial in subepidermal blister formation in experimental BP. PMID:17024247

Treatment of recalcitrant cicatricial pemphigoid with the tumor necrosis factor alpha antagonist etanercept.

PubMed

Sacher, Christopher; Rubbert, Andrea; König, Cathrin; Scharffetter-Kochanek, Karin; Krieg, Thomas; Hunzelmann, Nicolas

2002-01-01

The treatment of cicatricial pemphigoid is generally regarded as difficult and usually relies on individual clinical experience. Corticosteroids, as drugs of first choice, often have to be combined with steroid-sparing agents to prevent hazardous, long-term side effects. We describe a 72-year-old woman with long-standing cicatricial pemphigoid recalcitrant to established treatment regimens who responded rapidly and lastingly to therapy with the tumor necrosis factor alpha antagonist etanercept. To our knowledge, this is the first report of its use in the treatment of a bullous autoimmune disease.

Bullous Pemphigoid

MedlinePlus

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Bullous Pemphigoid

MedlinePlus

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A Th2-like cytokine response is involved in bullous pemphigoid. the role of IL-4 and IL-5 in the pathogenesis of the disease.

PubMed

Feliciani, C; Toto, P; Mohammad Pour, S; Coscione, G; Amerio, P; Amerio, P

1999-01-01

Bullous Pemphigoid is an autoimmune bullous disorder characterized by production of IgG against an hemidesmosomal antigen (230 kDa, 180 kDa) responsible for blistering of the skin. In the past several mediators have been implicated in the pathogenesis of the disease such as proteases and collagenases secreted by local inflammatory cells. In order to investigate the role of cytokines in BP, the cytokine pattern was evaluated by an immunohistochemical analysis and by reverse transcriptase polymerase chain reaction procedure in 13 BP patients. Cytokines examined were interleukin (IL)-2, IL-4, IL-5, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. The T cell inflammatory infiltrate was also characterized by monoclonal antibodies showing CD3+, CD4+ T cells with a perivascular and scattered distribution in lesional skin. IL-4 and IL-5 were detected in a similar distribution to the inflammatory infiltrate. IL-4 and IL-5 mRNA levels were also revealed by RT-PCR. Proinflammatory cytokines such as TNF-alpha, IL-6 and Th1-like cytokines (IL-2 and INF-gamma) were not detected neither as proteins nor as mRNA. Since IL-4 and IL-5 are important in eosinophil chemoattraction, maturation and functional activity, the presence of IL-4 and IL-5 in BP suggest that these cytokines could be important in the pathogenesis of the disease.

Bullous Pemphigoid

MedlinePlus

... They can be used in combination with potent topical steroid creams for more rapid relief. Oral steroids ( ... reduce the dose of medications to reasonably low levels. BP also often has a pattern of remissions ...

Epidermolysis Bullosa Acquisita: Autoimmunity to Anchoring Fibril Collagen

PubMed Central

Chen, Mei; Kim, Gene H.; Prakash, Lori; Woodley, David T.

2012-01-01

Epidermolysis bullosa acquisita (EBA) is a rare and acquired autoimmune subepidermal bullous disease of the skin and mucosa. EBA includes various distinct clinical manifestations resembling Bullous Pemphigus, Brunsting-Perry pemphigoid, or cicatricial pemphigoid. These patients have autoantibodies against type VII collagen, an integral component of anchoring fibrils, which are responsible for attaching the dermis to the epidermis. Destruction or perturbation of the normally functioning anchoring fibrils clinically results in skin fragility, blisters, erosions, scars, milia and nail loss, all features reminiscent of genetic dystrophic epidermolysis bullosa. These anti-type VII collagen antibodies are “pathogenic” because when injected into a mouse, the mouse develops an EBA-like blistering disease. Currently treatment is often unsatisfactory, however some success has been achieved with colchichine, dapsone, photopheresis, plasmaphresis, infliximab, rituximab and IVIG. PMID:21955050

Case Report of Bullous Pemphigoid following Fundus Fluorescein Angiography

PubMed Central

Demirci, Goktug; Demirci, Gulsen Tukenmez; Gulkilik, Gokhan

2010-01-01

Purpose To report a first case of bullous pemphigoid (BP) following intravenous fluorescein for fundus angiography. Clinical Features: A 70-year-old male patient was admitted to the intensive care unit with BP and sepsis. He reported a history of fundus fluorescein angiography with a pre-diagnosis of senile macular degeneration 2 months prior to presentation. At that time, fluorescein extravasated at the antecubital region. Following the procedure, pruritus and erythema began at the wrists bilaterally, and quickly spread to the entire body. The patient also reported a history of allergy to human albumin solution (Plamasteril®; Abbott) 15 years before, during bypass surgery. On dermatologic examination, erythematous patches were present on the scalp, chest and anogenital region. Vesicles and bullous lesions were present on upper and lower extremities. On day 2 of hospitalization, tense bullae appeared on the upper and lower extremities. The patient was treated with oral methylprednisolone 48 mg (Prednol®; Mustafa Nevzat), topical clobetasol dipropionate 0.05% cream (Dermovate®; Glaxo SmithKline), and topical 4% urea lotion (Excipial Lipo®; Orva) for presumptive bullous pemphigoid. Skin punch biopsy provided tissue for histopathology, direct immunofluorescence examination, and salt extraction, which were all consistent with BP. After 1 month, the patient was transferred to the intensive care unit with sepsis secondary to urinary tract infection; he died 2 weeks later from sepsis and cardiac failure. Conclusions To our knowledge, this is the first reported case of BP following fundus fluorescein angiography in a patient with known human albumin solution allergy. Consideration should be made to avoid fluorescein angiography, change administration route, or premedicate with antihistamines in patients with known human albumin solution allergy. The association between fundus fluorescein angiography and BP should be further investigated. PMID:20737052

Pembrolizumab-associated Mucous Membrane Pemphigoid in a Merkel cell carcinoma patient.

PubMed

Haug, V; Behle, V; Benoit, S; Kneitz, H; Schilling, B; Goebeler, M; Gesierich, A

2018-05-14

the anti-programmed death-1 (PD-1) antibody pembrolizumab, routinely used for treatment of metastatic melanoma or non-small cell lung cancer, was recently shown to have clinical meaningful activity in metastatic Merkel cell carcinoma (MCC). Several cases of bullous pemphigoid (BP) induced by PD-1 antibodies in melanoma have been reported so far. Here we report a case of oral mucous membrane pemphigoid (MMP) - a previously unknown, severe immune-related adverse event (irAE) occurring during pembrolizumab therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Utility of an interferon-gamma release assay for latent tuberculosis diagnosis in a case of bullous pemphigoid.

PubMed

Goodfellow, Alfred; Keeling, Douglas N; Hayes, Robert C; Webster, Duncan

2009-01-01

With increasing use of immunosuppressive therapy, including tumor necrosis factor alpha inhibitors, there is concern about infectious complications, including reactivation of latent Mycobacterium tuberculosis infection. Routine testing prior to administration of systemic immunosuppression includes the tuberculin skin test, which lacks sensitivity and specificity and may be difficult to interpret in the presence of extensive cutaneous disease. Treatment of individuals with latent tuberculosis infection is recommended when immunosuppressive medications are to be employed. We report a case in which a diagnosis of latent tuberculosis infection in a patient with extensive bullous pemphigoid was clarified by the use of an interferon-gamma release assay after equivocal tuberculin skin test results. Interferon-gamma release assays are useful adjuncts to the tuberculin skin test in the diagnosis of latent tuberculosis infection in the setting of extensive cutaneous disease.

Cutaneous Mucormycosis Following a Bullous Pemphigoid Flare in a Chronic Lymphocytic Leukemia Patient on Ibrutinib.

PubMed

Stein, Matthew K; Karri, Saradasri; Reynolds, Jackson; Owsley, Jeff; Wise, Austin; Martin, Mike G; Zare, Fereshteh

2018-04-01

While the recent development of novel therapeutics in oncology, such as small molecule kinase inhibitors (SMKIs), has enabled our ability to target disease-specific molecular pathways, the prolonged impact of these agents on the immune system and infectious risk remains to be seen. We present a 68-year-old male with refractory chronic lymphocytic leukemia (CLL) on ibrutinib monotherapy for 3 years who developed extensive cutaneous mucormycosis following a severe bullous pemphigoid (BP) flare. He received amphotericin B for 4 weeks and was continued on posaconazole with resolution of his mucormycosis infection. Consistent with a growing evidence of literature identifying opportunistic fungal infections in patients on ibrutinib therapy, providers should be cognizant of medical comorbidities that may predispose to such infections and explore methods of prevention before starting ibrutinib and other SMKIs.

Bullous lichen planus - a review.

PubMed

Liakopoulou, Angeliki; Rallis, Efstathios

2017-03-31

Bullous lichen planus is a rare variant of lichen planus. It is characterized by vesicles or bullae, which usually develop in the context of pre-existing LP lesions. It is often misdiagnosed and should be differentiated from other subepidermal bullous diseases especially lichen planus pemphigoides. The diagnosis is based on clinical suspicion and is confirmed by histopathology and immunofluoresence. The clinical features of bullous lichen planus include typical lichen planus lesions, accompanied by the formation of bullae on the affected or perilesional skin. This is evident on histology, with alteration of the dermo-epidermal junction and intrabasal bullae as a consequence of extensive inflammation. The histologic features in conjunction with the negative immunofluoresence indicate that bullous lichen planus is a form of "hyper-reactive lichen planus" rather than a distinct entity. There is no standard treatment of bullous lichen planus. Topical and systemic corticosteroids, dapsone and acitretin have been described as effective choices.

Relationship between theoretical molecular weight and blister fluid/serum ratio of cytokines and five other molecules evaluated in patients with bullous pemphigoid.

PubMed

D'Auria, L; Pimpinelli, F; Ferraro, C; D'Ambrogio, G; Giacalone, B; Bellocci, M; Ameglio, F

1998-01-01

Bullous pemphigoid (BP) blisters contain several molecules, some of which spread into the blisters from the interstitial fluid, while others are produced locally and migrate into the circulation. The calculation of the ratios between blister/serum concentrations may help to distinguish between these two types of molecules. The rules regulating the diffusion of the molecules have been described only in suction blisters, where the theoretical molecular weight (MW) represents one of the principal influencing factors. The aim of the present study was to analyse the relationship between theoretical MWs and the ratios of concentrations of several molecules evaluated both in sera and in blister fluids. Eight cytokines (interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-10, tumor necrosis factor-alpha, oncostatin-M and vascular endothelial growth factor), two acute phase reactants (alpha-1 acid glycoprotein, haptoglobin), albumin, one soluble membrane molecule with adhesion functions (sICAM-1) and the eosinophil cathionic protein (ECP) were measured in samples from 15 patients affected with BP by means of commercially available tests. The data suggest that the MW may influence the rate of diffusion throughout the blister, both in input and output directions, despite the discontinuity observed at the basement membrane level on the BP blister floor.

A case of bullous pemphigoid ınduced by vildagliptin.

PubMed

Keseroglu, Havva Ozge; Taş-Aygar, Gamze; Gönül, Müzeyyen; Gököz, Ozay; Ersoy-Evans, Sibel

2017-06-01

Bullous pemfigoid (BP), an autoimmune disorder, can also be induced by some medications. Vildagliptin is a new drug used to treat diabetes mellitus (DM). Recently, a few cases of vildagliptin-induced BP have been described in the literature. We report a patient with BP in which vildagliptin was thought to be as a possible causative agent. The awareness of BP development risk during gliptin therapy can prevent unnecessary usage of systemic drugs with serious side effects.

Increased serum IL-6, TNF-alpha and IL-10 levels in patients with bullous pemphigoid: relationships with disease activity.

PubMed

D'Auria, L; Mussi, A; Bonifati, C; Mastroianni, A; Giacalone, B; Ameglio, F

1999-01-01

The present report analyzes the serum levels of three cytokines, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in 15 patients with bullous pemphigoid (BP) (compared with 20 healthy controls) to evaluate a possible involvement of these biological modulators in the clinical expression of this disease. BP is a rare bullous disease of autoimmune origin with evidence of inflammatory processes that cause skin lesions with local increase of various pro-inflammatory mediators. Determination of cytokine concentrations were obtained employing commercially available ELISA kits. The sera of BP patients showed increased levels of these three cytokines (P < 0.01). When the number of skin lesions (blisters and/or erosion) of each patient, employed as a marker of disease activity, was correlated with the serum levels of IL-6 and TNF-alpha, significant correlations were found (IL-6: P < 0.01 and TNF-alpha: P < 0.01, respectively), suggesting a possible role of these mediators in the development of BP blisters. The serum levels of IL-6 also correlated (P = 0.01 with those of serum C reactive protein (CRP), an acute-phase protein induced by IL-6 in hepatocytes. In addition, serum TNF-alpha and sE-selectin (an adhesion molecule previously reported to be increased by this cytokine) levels were also correlated (P < 0.05). On the basis of these data, it may be indicated that at least IL-6 and TNF-alpha are associated with the clinical expression of BP and that the endothelial activation (possibly induced by the TNF-alpha activity), seems to be an important phase of this dermatosis.

Usefulness of a Simple Immunohistochemical Staining Technique to Differentiate Anti-p200 Pemphigoid From Other Autoimmune Blistering Diseases: A Report of 2 Cases.

PubMed

García-Díez, I; Martínez-Escala, M E; Ishii, N; Hashimoto, T; Mascaró Galy, J M; Pujol, R M; Herrero-González, J E

Anti-p200 pemphigoid is a rare autoimmune subepidermal blistering disease characterized by the presence of circulating immunoglobulin G antibodies directed against laminin gamma-1, a 200-kDa protein located in the lamina lucida of the basement membrane. We review the clinical, histopathological and immunological characteristics of the first 2 cases described in Spain. Anti-p200 pemphigoid shares histopathological and immunopathological findings with epidermolysis bullosa acquisita, the main entity in the differential diagnosis. However, its management follows the same guidelines as those used for bullous pemphigoid. The diagnosis is confirmed by immunoblotting, which is a complex technique available in few centers. We propose the immunohistochemical detection of collagen type IV on the floor of the blister, combined with standard immunofluorescence techniques, as a simple, accessible alternative to differentiate anti-p200 pemphigoid from epidermolysis bullosa acquisita. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Accuracy of molecular diagnostics in pemphigus and bullous pemphigoid: comparison of commercial and modified mosaic indirect immunofluorescence tests as well as enzyme-linked immunosorbent assays.

PubMed

Gornowicz-Porowska, Justyna; Seraszek-Jaros, Agnieszka; Bowszyc-Dmochowska, Monika; Kaczmarek, Elżbieta; Pietkiewicz, Paweł; Bartkiewicz, Paweł; Dmochowski, Marian

2017-02-01

Pemphigus and bullous pemphigoid (BP) are identified by autoantibodies (abs) against desmoglein 1, 3 (DSG1/3) and BP180/BP230, respectively. A novel mosaic to indirect immunofluorescence (IIF) using purified BP180 recombinant proteins spotted on slide and transfected cells expressing BP230, DSG1, DSG3 is available. The commercial (IgG detection) and modified (IgG4 detection) mosaic for indirect immunofluorescence (IIFc - IIF commercial, IIFm - IIF modified) and IgG ELISAs were evaluated in pemphigus and bullous pemphigoid (BP) molecular diagnostics. To compare diagnostic accuracy of commercial (IgG detection) and modified (IgG4 detection) mosaic IIF assay and to examine the diagnostic value of ELISAs in relation to mosaic IIF in routine laboratory diagnostics of pemphigus and BP. Sera from 37 BP and 19 pemphigus patients were studied. Associations between tests were assessed using Fisher's exact test. There are associations between the positive/negative samples detected by IIFc with desmoglein1 (DSG1)/desmoglein3 (DSG3)/BP230 transfected cells and ELISAs and no association between anti-BP180 IgG detection by IIFc and ELISA. IIFm with DSG1 and DSG3 showed both 100% sensitivity and 100% and 78% specificity, respectively, and 100% and 83% positive predictive value in relation to IIFc. IIFm with BP230 had 87% specificity, 55% sensitivity, whereas IIFm with BP180 had a 100% sensitivity and 13% specificity in relation to IIFc. The IIFc with DSG1/DSG3/BP230 transfected cells, excluding BP180 spots, is an alternative method to ELISA in pemphigus/BP diagnostics. IgG4 antibodies, both pathogenically and diagnostically important, are inconsistently detectable with IIFm.

A randomized controlled trial to compare the safety and effectiveness of doxycycline (200 mg daily) with oral prednisolone (0.5 mg kg(-1) daily) for initial treatment of bullous pemphigoid: a protocol for the Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) Trial.

PubMed

Chalmers, J R; Wojnarowska, F; Kirtschig, G; Nunn, A J; Bratton, D J; Mason, J; Foster, K A; Whitham, D; Williams, H C

2015-07-01

Bullous pemphigoid (BP) is the most common autoimmune blistering disease in older people, and is associated with significant morbidity and mortality. Oral corticosteroids are usually effective but the side-effects are thought to contribute to the high morbidity and mortality rate. Treatment with oral tetracyclines may be effective but high-quality, randomized controlled trials (RCTs) are needed to confirm this. To compare the effectiveness and safety of two strategies for treating BP. This is a two-arm, parallel group, 52-week RCT comparing doxycycline with prednisolone for initial treatment of BP. Dose is fixed for the initial 6 weeks of treatment (doxycycline 200 mg daily; prednisolone 0.5 mg kg(-1) daily), after which it can be adjusted according to need. A total of 256 patients with BP will be recruited in the U.K. and Germany. The primary outcomes are: (i) effectiveness (assessor-blinded blister count at 6 weeks) and (ii) safety [proportion of patients experiencing ≥ grade 3 adverse events (i.e. severe, life: threatening or fatal) related to trial medication during the year of follow-up]. Primary effectiveness analysis will be an assessment of whether doxycycline can be considered noninferior to prednisolone after 6 weeks of treatment. Primary safety analysis is a superiority analysis at 12 months. Secondary outcomes include longer-term assessment of effectiveness, relapse rates, the proportion of patients experiencing any grade of adverse events related to treatment, quality of life and cost-effectiveness. The trial will provide good evidence for whether the strategy of starting BP treatment with doxycycline is a useful alternative to prednisolone. © 2015 British Association of Dermatologists.

Acute inflammatory neuropathy with monoclonal anti-GM2 IgM antibodies, IgM-κ paraprotein and additional autoimmune processes in association with a diffuse large B-cell non-Hodgkin's lymphoma.

PubMed

Milnik, Annette; Roggenbuck, Dirk; Conrad, Karsten; Bartels, Claudius

2013-01-21

Lymphoproliferative disorders are often associated with autoimmune processes preceding or following the occurrence of a lymphoma. Here, we describe a patient with a history of recurrent diffuse large B-cell non-Hodgkin's lymphoma who suffered from an acute inflammatory neuropathy with specific monoclonal anti-GM2 IgM antibodies and associated IgM-κ paraprotein. It was possible in this case to prove that both, anti-GM2 IgM antibodies and IgM-κ paraprotein, share the same binding characteristic. In addition, the patient possibly suffered from an immune thrombocytopenia and an early-stage bullous pemphigoid with anti-BP-230 IgG antibodies. Intravenous immunoglobulin and plasmapheresis alleviated the acute neuropathy and thrombocytopenia, while the bullous pemphigoid has been aggravated. In summary, the simultaneous occurrence of multiple autoimmune processes was a sign of a dysfunctional immune system preceding the relapse of a B-cell non-Hodgkin's lymphoma.

Increased sensitivity and high specificity of indirect immunofluorescence in detecting IgG subclasses for diagnosis of bullous pemphigoid.

PubMed

Jankásková, J; Horváth, O N; Varga, R; Arenberger, P; Schmidt, E; Ruzicka, T; Sárdy, M

2018-04-01

Indirect immunofluorescence (IIF) microscopy on monkey oesophagus is an important assay for the diagnosis of bullous pemphigoid (BP). Its relatively low sensitivity (60-80%) may be partly due to insufficient detection of minor IgG subclasses. To determine the operating characteristics of an IgG subclass in IIF. We designed a retrospective, dual-centre, controlled cohort study on sera from 64 BP sera that had been rated as false negatives by traditional IIF microscopy, and assessed circulating IgG 1 , IgG 3 and IgG 4 autoantibodies. The sensitivities of IIF in detecting IgG 1 , IgG 3 , IgG 4 and all three in combination were 45.3%, 18.8%, 32.8% and 48.4%, respectively. Specificities were > 97%. Detection of IgG subclass (especially IgG 1 and IgG 4 ) autoantibodies by IIF on monkey oesophagus can significantly improve diagnostic performance of IIF microscopy for diagnosis of BP. © 2018 British Association of Dermatologists.

Sensitivity of direct immunofluorescence in oral diseases. Study of 125 cases.

PubMed

Sano, Susana Mariela; Quarracino, María Cecilia; Aguas, Silvia Cristina; González, Ernestina Jesús; Harada, Laura; Krupitzki, Hugo; Mordoh, Ana

2008-05-01

Direct immunofluorescence (DIF) is widely used for the diagnosis of bullous diseases and other autoimmune pathologies such as oral lichen planus. There is no evidence in the literature on how the following variants influence the detection rate of DIF: intraoral site chosen for the biopsy, perilesional locus or distant site from the clinical lesion, number of biopsies and instrument used. to determine if the following variants influenced the sensitivity (detection rate): intraoral site chosen for the biopsy, perilesional or distant site from the clinical lesion, number of biopsies and instrument used (punch or scalpel). A retrospective study was done at the Cátedra de Patología y Clínica Bucodental II at the Facultad de Odontología, Universidad de Buenos Aires; 136 clinical medical histories were revised for the period March 2000 - March 2005 corresponding to patients with clinical diagnosis of OLP and bullous diseases (vulgar pemphigus, bullous pemphigoid and cicatricial pemphigoid). DIF detection rate was 65.8% in patients with OLP, 66.7% in cicatricial pemphigoid patients, in bullous pemphigoid 55.6%, in pemphigus vulgaris 100%, and in those cases in which certain diagnosis could not be obtained, the DIF positivity rate was 45.5% (Pearson chi(2) (4)= 21.5398 Pr= 0.000). There was no statistically significant difference between the different sites of biopsy (Fisher exact test: 0.825). DIF detection rate in perilesional biopsies was 66.1% and in those distant from the site of clinical lesion was 64.7% (Pearson chi(2) v1)= 0.0073 Pr= 0.932. When the number of biopsies were incremented, DIF detection rate also incremented (Pearson chi(2) = 8.7247 Pr= 0.003). The biopsies taken with punch had a higher detection rate than those taken with scalpel (39.1% versus 71.7%) (Pearson chi(2) = 49.0522 Pr= 0.000). While not statistically significant, the tendency outlined in this study indicates there are intraoral regions in which the detection rate of the DIF technique is higher than others: mouth floor, hard palate, superior labial mucosa, ventral face of tongue. This finding could allow a choice of accessible locations and easy operator manipulation, even in distant places from the clinical lesion. Perilesional biopsies have a detection rate similar to those taken distant from the clinical lesion, and those taken with punch have a higher sensitivity rate than those taken with scalpel (both differences were statistically significant).

Use of Topical Corticosteroids in Dermatology: An Evidence-based Approach

PubMed Central

Das, Anupam; Panda, Saumya

2017-01-01

Topical corticosteroids (TCs) are the pillars of dermatotherapeutics. These drugs are the “magic molecules,” provided they are used judiciously and appropriately, following a rational prescription. On exhaustive literature search in multiple databases, we found a significant evidence favoring the use of TCs in atopic eczema, localized vitiligo, psoriasis, chronic hand eczema, and localized bullous pemphigoid. However, contrary to conventional wisdom, we did not find any high-level scientific evidence in support of prescribing TCs in cutaneous lichen planus, sarcoidosis, and seborrhoeic dermatitis. Besides, evidence clearly advocates judicious use of mild-to-moderate corticosteroids (if required) in pregnancy and lactation and there is no risk of any fetal abnormality. PMID:28584365

Novel alternative splicings of BPAG1 (bullous pemphigoid antigen 1) including the domain structure closely related to MACF (microtubule actin cross-linking factor).

PubMed

Okumura, Masayo; Yamakawa, Hisashi; Ohara, Osamu; Owaribe, Katsushi

2002-02-22

BPAG1 (bullous pemphigoid antigen 1) was originally identified as a 230-kDa hemidesmosomal protein and belongs to the plakin family, because it consists of a plakin domain, a coiled-coil rod domain and a COOH-terminal intermediate filament binding domain. To date, alternatively spliced products of BPAG1, BPAG1e, and BPAG1n are known. BPAG1e is expressed in epithelial tissues and localized to hemidesmosomes, on the other hand, BPAG1n is expressed in neural tissues and muscles and has an actin binding domain at the NH(2)-terminal of BPAG1e. BPAG1 is also known as a gene responsible for Dystonia musculorum (dt) neurodegeneration syndrome of the mouse. Another plakin family protein MACF (microtubule actin cross-linking factor) has also an actin binding domain and the plakin domain at the NH(2)-terminal. However, in contrast to its high homology with BPAG1 at the NH(2)-terminal, the COOH-terminal structure of MACF, including a microtubule binding domain, resembles dystrophin rather than plakins. Here, we investigated RNAs and proteins expressed from the BPAG1 locus and suggest novel alternative splicing variants, which include one consisting of the COOH-terminal domain structure homologous to MACF. The results indicate that BPAG1 has three kinds of cytoskeletal binding domains and seems to play an important role in linking the different types of cytoskeletons.

[Chronic mucosynechial pemphigoid: so-called ocular pemphigus].

PubMed

Zingirian, M

1976-01-01

The so-called ocular pemphigus is an oculocutaneomucosal disease, the clinical manifestations of which have been recognized for over a century while its recognition as a nosological and histopathological unit is quite recent. The clinical picture in the eye consists essentially of progressive scar contraction which, preceded by a transient bullous phase, leads to symblepharon, entropion and trichiasis. Corneal complications, such as bullous eruption, erosions, proliferation of vasculoconnective tissue, supervene later. The final appearance is that of complete xerosis with total symblepharon producing a typical 'statute eye'. This local process may be accompanied by bullous lesions of the skin and mucous membranes but the general condition of the patient invariably remains good. In the advanced stages of the disease the appearance is described as 'pemphigoid facies'. The nosological place of ocular pemphigus has been a matter of debate. At various times it has been identified with pemphigus vulgaris, dermatitis herpetiformis of Duhring-Brocq, erythema multiforme of Hebra, Stevens-Johnson syndrome, syphilitic dermatitis bullosa and other bullous dermatoses. At present the condition is universally recognized as a clinical entity, referred to as chronic mucosynechial pemphigoid (CMSP). The anatomopathological picture is quite peculiar. The elementary lesion is a sub-epidermic bulla, hence easily distinguished from that of pemphigus vulgaris, which is situated in the Malpighian layer. This difference applies to the lesions of the skin as well as to those of the mucous membranes including the conjuctiva. In the conjunctiva, epithelial changes suggestive of its epidermization were demonstrated. The Malpighian layer shows a high glycogen and DNA content with overall reduction in enzyme activity. The dermis shows infiltration by lymphocytes, histiocytes and plasma cells, and a considerable increase in hyaluronic acid content. There are many areas of dermoepidermal separation with formation of bullae and the basal membrane is often missing. In some cases, in the centre of the bullae, we were able to demonstrate one or more lumps, consisting almost exclusively of hyaluronic acid, probably filtered in from the dermis across the altered basal membrane. Similar changes are met with also in other mucous membranes, that of buccal cavity in particular, even in ostensibly healthy areas. The histological and histochemical findings are sufficiently typical to justify early diagnostic biopsy in all suspected cases. The aetiology of the CMSP still remains debated. Two theories are under consideration at the moment, viral and autoimmune. The main argument in favour of the viral theory is that a cytopathogenic agent can be isolated from the blood of patients with different dermatoses of the pemphigus group, including the CMSP, whose cytotoxic activity can be passed through and potentiated by passage in cell cultures...

Prothrombotic state and impaired fibrinolysis in bullous pemphigoid, the most frequent autoimmune blistering disease

PubMed Central

Marzano, A V; Tedeschi, A; Polloni, I; Crosti, C; Cugno, M

2013-01-01

Bullous pemphigoid (BP) is a potentially life-threatening autoimmune blistering disease that is burdened with an increased risk of cardiovascular events. In BP, there is an interplay between inflammation and coagulation both locally, which contributes to skin damage, and systemically, which leads to a prothrombotic state. Fibrinolysis is an important defence mechanism against thrombosis, but has only been studied locally in BP and no systemic data are available. The aim of this observational study was to evaluate systemic fibrinolysis and coagulation activation in patients with BP. We measured parameters of fibrinolysis and coagulation by immunoenzymatic methods in plasma from 20 patients with BP in an active phase and during remission after corticosteroid treatment. The controls were 20 age- and sex-matched healthy subjects. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1) antigen, PAI-1 activity and tissue plasminogen activator (t-PA) antigen were significantly higher in the BP patients with active disease than in healthy controls (P = 0·0001 for all), as were the plasma levels of the fibrin fragment d-dimer and prothrombin fragment F1+2 (P = 0·0001 for both). During remission after treatment, levels of PAI-1 antigen and PAI-1 activity decreased significantly (P = 0·008 and P = 0·006, respectively), and there was also a significant decrease in plasma levels of d-dimer (P = 0·0001) and F1+2 (P = 0·0001). Fibrinolysis is inhibited in patients with active BP, due mainly to an increase in plasma levels of PAI-1. Corticosteroids not only induce the regression of BP lesions, but also reduce the inhibition of fibrinolysis, which may contribute to decreasing thrombotic risk. PMID:23199326

Cytokine gene polymorphisms in bullous pemphigoid in a Chinese population.

PubMed

Chang, Y T; Liu, H N; Yu, C W; Lin, M W; Huang, C H; Chen, C C; Liu, M T; Lee, D D; Wang, W J; Tsai, S F

2006-01-01

Bullous pemphigoid (BP) is an autoimmune bullous disease mostly associated with autoantibodies to the hemidesmosomal BP autoantigens BP180 and BP230. High levels of interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been detected in skin lesions or sera of patients with BP. Cytokine gene polymorphisms may affect cytokine production and contribute to susceptibility to autoimmune diseases. Until now, no cytokine gene polymorphism study has been conducted on patients with BP. We aimed to determine whether the genetic polymorphisms of the cytokine genes might influence the development of BP. DNA samples were obtained from 96 BP patients and 174 control subjects. Using direct sequencing and microsatellite genotyping, we examined 23 polymorphisms in 11 cytokine genes including the IL-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, IL-13, IL-4 receptor, TNF-alpha and IFN-gamma genes. Although the BP patients were more likely to carry the -511T and -31C alleles of the IL-1beta gene (P = 0.04), the significance disappeared after correction for multiple testing (Pc). There was complete linkage disequilibrium between the -511T and -31C alleles of the IL-1beta gene. In female patients with BP, the associations with IL-1beta (-511T) and (-31C) alleles were much stronger (68% vs. 40.6%, odds ratio = 3.11, Pc = 0.006). No significantly different allelic and genotypic distributions of other cytokine gene polymorphisms could be found between the patients with BP and controls. Moreover, no association with the extent of disease involvement (localized or generalized) was observed. The IL-1beta (-511) and (-31) polymorphisms were significantly associated with BP in women. The other genetic polymorphisms of cytokine genes that we analysed do not appear to be associated with BP susceptibility in our Chinese population.

Increased Activity and Apoptosis of Eosinophils in Blister Fluids, Skin and Peripheral Blood of Patients with Bullous Pemphigoid.

PubMed

Engmann, Judith; Rüdrich, Urda; Behrens, Georg; Papakonstantinou, Eleni; Gehring, Manuela; Kapp, Alexander; Raap, Ulrike

2017-04-06

Bullous pemphigoid (BP) is an autoimmune blistering skin disease that is more common in elderly individuals. The aim of this study was to determine the functional activity of eosinophils in patients with BP compared with healthy donors. Blood, skin and blister-derived eosinophils were strongly activated in patients with BP, seen by increased surface expression of CD69 compared with controls. CD11b was also increased in BP blood eosinophils, which may explain the striking accumulation of eosinophils in BP (1×106 per ml blister fluid). Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in blister fluid. BP eosinophils also released IL-6, IL-8 and IL-1α in BP blister fluids. Apoptosis in cultivated BP eosinophils was increased and accompanied by enhanced surface externalization of CD95. Caspase 3 positive eosinophils in lesional BP skin and blister fluid also showed the initiation of apoptosis. These results reveal novel pathophysiological aspects of BP, with a strong activation pattern and increased apoptosis of eosinophils in the peripheral blood, skin and blister fluids.

BP180 Is Critical in the Autoimmunity of Bullous Pemphigoid

PubMed Central

Liu, Yale; Li, Liang; Xia, Yumin

2017-01-01

Bullous pemphigoid (BP) is by far the most common autoimmune blistering dermatosis that mainly occurs in the elderly. The BP180 is a transmembrane glycoprotein, which is highly immunodominant in BP. The structure and location of BP180 indicate that it is a significant autoantigen and plays a key role in blister formation. Autoantibodies from BP patients react with BP180, which leads to its degradation and this has been regarded as the central event in BP pathogenesis. The consequent blister formation involves the activation of complement-dependent or -independent signals, as well as inflammatory pathways induced by BP180/anti-BP180 autoantibody interaction. As a multi-epitope molecule, BP180 can cause dermal–epidermal separation via combining each epitope with specific immunoglobulin, which also facilitates blister formation. In addition, some inflammatory factors can directly deplete BP180, thereby leading to fragility of the dermal–epidermal junction and blister formation. This review summarizes recent investigations on the role of BP180 in BP pathogenesis to determine the potential targets for the treatment of patients with BP. PMID:29276517

Autoimmune responses in patients with linear IgA bullous dermatosis: both autoantibodies and T lymphocytes recognize the NC16A domain of the BP180 molecule.

PubMed

Lin, Mong-Shang; Fu, Chang-Ling; Olague-Marchan, Monica; Hacker, Mary K; Zillikens, Detlef; Giudice, George J; Fairley, Janet A

2002-03-01

Linear IgA bullous disease (LABD) is an autoimmune skin disease characterized by subepidermal blisters and IgA autoantibodies directed against the epidermal basement membrane zone (BMZ) of the skin. Various antigens have been identified as targets of IgA autoantibodies including BP180, a type II glycoprotein that spans the BMZ and lamina lucida. Previously, we have identified a subset of LABD patients whose sera contained IgA antibodies against the 16th noncollagenous (NC16A) domain of BP180. NC16A was previously shown to harbor epitopes that are recognized by both autoantibodies and T cells from patients with bullous pemphigoid and herpes gestationis and is thought to be associated with the development of these immunobullous diseases. The aim of this study was to determine whether T lymphocytes from LABD patients with anti-NC16A IgA autoantibodies respond to epitopes in the same region of the BP180 protein. Indeed, of the four LABD patients in our study, all had T cells that specifically proliferated in response to NC16A. Moreover, two subfragments of NC16A were identified as the predominant targets of LABD T cells. Further analysis of T cell lines and clones derived from these patients revealed that these cells express a CD4 memory T cell phenotype and secrete a Th1/Th2 mixed-cytokine profile, characteristics similar to those of T cells in bullous pemphigoid patients. Our data suggest that the BP180 protein, typically the NC16A region, is the common target of both cellular and humoral immune responses in some LABD patients. This information helps to further elucidate the autoimmune mechanisms in this disease.

Lichen planus pemphigoides treated with ustekinumab.

PubMed

Knisley, Raymond R; Petropolis, Angelo A; Mackey, Vernon T

2017-12-01

A 71-year-old woman presented with pink to violaceous, flat-topped, polygonal papules on the volar wrists, extensor elbows, and bilateral lower legs of 3 years' duration. She also had erythematous, violaceous, infiltrated plaques with microvesiculation on the bilateral thighs of several months' duration. She reported pruritus, burning, and discomfort. Her medical history included type 2 diabetes mellitus, hypertension, and asthma with no history of skin rashes. Workup revealed lichen planus pemphigoides (LPP), a rare papulosquamous and vesiculobullous dermatosis that shares features of both lichen planus (LP) and bullous pemphigoid (BP). Despite multiple traditional therapies, her disease continued to progress, further developing mucosal disease. After a review of the literature on LP, BP, and LPP, it was noted that tumor necrosis factor α (TNF-α), along with other cytokines, plays a pivotal role in all 3 diseases. After several conventional systemic therapies failed, we treated our patient with ustekinumab with favorable results.

Incidence of autoimmune bullous diseases in Serbia: a 20-year retrospective study.

PubMed

Milinković, Mirjana V; Janković, Slavenka; Medenica, Ljiljana; Nikolić, Miloš; Reljić, Vesna; Popadić, Svetlana; Janković, Janko

2016-10-01

While most previous surveys on the clinico-epidemiological features of autoimmune bullous diseases (AIBDs) have predominantly focused on a single disease entity or just one disease group, there have been only few studies examining the incidence of various AIBDs. In the present study, we set out to determine the spectrum of AIBDs, to estimate the incidence of the most common AIBDs, and to examine their temporal trends in Central Serbia over a period of 20 years. We retrospectively recruited 1,161 new AIBD cases diagnosed in Central Serbia during the period from January 1991 to December 2010. The diagnosis was based on strict clinical, histological, and immunohistological evaluation. The incidence rates were: 4.35 per million population/year (pmp/year) for pemphigus, 4.47 pmp/year for pemphigoid, 1.42 pmp/year for dermatitis herpetiformis (DH), 0.25 pmp/year for linear IgA disease, and 0.08 pmp/year for epidermolysis bullosa acquisita. In the period observed, age-adjusted incidence rates significantly increased for pemphigus and particularly for pemphigoid, whereas they decreased, albeit not significantly, for DH. For the first time, our study evaluates the incidence rates of the entire spectrum of AIBDs in Serbia, and examines their temporal trends over a 20-year period. To the best of our knowledge, our finding of similar incidence rates for pemphigus and pemphigoid has previously not been reported. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

[Pemphigus herpetiformis: a clinical variant of pemphigus vulgaris].

PubMed

Bauer, R; Orfanos, C E

1980-10-01

Two female patients are reported in whom the clinical picture closely corresponded to dermatitis herpetiformis Duhring or bullous pemphigoid, while acantholytic changes were present histologically. Indirect immunofluorescence revealed circulating pemphigus antibodies. Direct fluorescence showed deposits of IgG and complement in the intercellular space of the affected areas. One of the two patients responded well to DDS. There have been reports in the recent literature on bullous dermatoses, which can be regarded as morphological variants of pemphigus vulgaris. The term pemphigus herpetiformis is used here to designate these variants. The diagnosis can only be made by histological and immunological examinations in connection with the clinical picture.

Usefulness of Enzyme-linked Immunosorbent Assay Using Recombinant BP180 and BP230 for Serodiagnosis and Monitoring Disease Activity of Bullous Pemphigoid

PubMed Central

Lee, Eui Hyung; Kim, Yeon Hee; Kim, Sinyoung; Kim, Song-ee

2012-01-01

Background Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease associated with autoantibodies against BP180 and BP230. Enzyme-linked immunosorbent assay (ELISA) is a sensitive tool for the detection of immunoglobulin G (IgG) anti-BP180 and anti-BP230 autoantibodies. Objective The aim of this study was to evaluate the usefulness of ELISA for diagnosing and monitoring the disease activity of BP. Methods We evaluated serum IgG levels of anti-BP180 and anti-BP230 autoantibodies in 47 BP patients, 16 epidermolysis bullosa aquisita patients, and 15 healthy volunteers using ELISA. Through retrospective review of the medical records, the clinical characteristics of BP including disease activity, duration, pruritus severity and peripheral blood eosinophil counts were assessed. Results The sensitivity of BP180 ELISA was 97.9%, BP230 ELISA 72.3%, and a combination of the two was 100%. The specificity of BP180 ELISA was 90.3%, BP230 ELISA 100%, and a combination of the two was 90.3%. BP180 ELISA scores showed strong associations with disease activity, pruritus severity, peripheral blood eosinophil counts, and disease duration, whereas BP230 ELISA scores did not. Conclusion BP180 and BP230 ELISAs are highly sensitive methods for the diagnosis of BP, and BP180 ELISA, in particular, is a sensitive tool for monitoring the disease activity of BP. PMID:22363155

Integrating longitudinal serum IL-17 and IL-23 follow-up, along with autoantibodies variation, contributes to predict bullous pemphigoid outcome

PubMed Central

Plée, Julie; Le Jan, Sébastien; Giustiniani, Jérôme; Barbe, Coralie; Joly, Pascal; Bedane, Christophe; Vabres, Pierre; Truchetet, François; Aubin, François; Antonicelli, Frank; Bernard, Philippe

2015-01-01

Bullous pemphigoid (BP) is an inflammatory autoimmune bullous disease involving cytokines and proteases in the process of blister formation. Recently, IL-17 and IL-23 were evidenced in lesional skin and serum of BP patients at time of diagnosis, but their involvement in disease outcome has still not been investigated yet. We then analysed IL-17 and IL-23 serum levels during the first months of follow-up upon treatment. Compared with age- and sex- matched controls, high levels of IL-23 were observed at baseline in BP patients serum (P < 0.01), while IL-17 levels was not. However, some BP patients expressed high IL-17 serum level, independently of disease severity. In these patients, those with ongoing remission reduced IL-17 concentration upon treatment (P < 0.001), whereas IL-17 level remained elevated in patients who relapsed. Meanwhile, IL-23 serum levels increased during the first month of treatment in BP patients who later relapsed (P < 0.01) and MMP-9 serum level was not controlled. Accordingly, we found that both IL-17 and IL-23 increased MMP-9 secretion from leukocytes in-vitro. Then, we showed that elevated IL-17/IL-23 serum concentrations helped to discriminate BP patients who later relapsed. Such uncontrolled inflammatory response raises the question whether these molecules could become biological target for BP patients resistant to steroid treatment. PMID:26656739

[Effects of jingui shenqi pill combined prednisone on expression of glucocorticoid receptor and its clinical effect in treating bullous pemphigoid patients].

PubMed

Liu, Bao-guo; Li, Zhi-ying; Du, Ming

2006-10-01

To investigate the effect of Jingui Shenqi Pill (JSP) on the expression of glucocorticoid receptor (GR) in the skin lesion and its clinical effect in treating bullous pemphigoid (BP) patients. Thirty BP patients were randomly divided into the treatment group (n=15) treated with JSP plus prednisone and the prednisone group (n=15) with prednisone alone both for 4 weeks. And a normal control group was set up also. Expressions of GR-alpha and GR-beta in the skin lesion of BP patients and the normal skin of the normal control were detected by immunohistochemical assay. Results The total effective rate was 93.33% in the treatment group, significantly higher than that in the prednisone group which was 73.33% (P < 0.05); GR-alpha expression was higher in the treatment group than that in other two groups (P < 0.01), while GR-beta expression in the treatment group was lower than that in the prednisone group (P < 0.01). JSP could increase GR-alpha expression and decrease GR-beta expression in the skin lesion of BP patients, so as to improve sensitivity of skin to glucocorticoid.

Subepidermal Blistering Induced by Human Autoantibodies to BP180 Requires Innate Immune Players in a Humanized Bullous Pemphigoid Mouse Model

PubMed Central

Liu, Zhi; Sui, Wen; Zhao, Minglang; Li, Zhuowei; Li, Ning; Thresher, Randy; Giudice, George J.; Fairley, Janet A.; Sitaru, Cassian; Zillikens, Detlef; Ning, Gang; Marinkovich, Peter; Diaz, Luis A.

2008-01-01

Bullous pemphigoid (BP) is a cutaneous autoimmune inflammatory disease associated with subepidermal blistering and autoantibodies against BP180, a transmembrane collagen and major component of the hemidesmosome. Numerous inflammatory cells infiltrate the upper dermis in BP. IgG autoantibodies in BP fix complement and target multiple BP180 epitopes that are highly clustered within a non-collagen linker domain, termed NC16A. Anti-BP180 antibodies induce BP in mice. In this study, we generated a humanized mouse strain, in which the murine BP180NC14A is replaced with the homologous human BP180NC16A epitope cluster region. We show that the humanized NC16A (NC16A+/+) mice injected with anti-BP180NC16A autoantibodies develop BP-like subepidermal blisters. The F(ab′)2 fragments of pathogenic IgG fail to activate complement cascade and are no longer pathogenic. The NC16A+/+ mice pretreated with mast cell activation blocker or depleting of complement or neutrophils become resistant to BP. These findings suggest that the humoral response in BP critically depends on innate immune system players. PMID:18922680

Humoral Epitope Spreading in Autoimmune Bullous Diseases

PubMed Central

Didona, Dario; Di Zenzo, Giovanni

2018-01-01

Autoimmune blistering diseases are characterized by autoantibodies against structural adhesion proteins of the skin and mucous membranes. Extensive characterization of their autoantibody targets has improved understanding of pathogenesis and laid the basis for the study of antigens/epitopes diversification, a process termed epitope spreading (ES). In this review, we have reported and discussed ES phenomena in autoimmune bullous diseases and underlined their functional role in disease pathogenesis. A functional ES has been proposed: (1) in bullous pemphigoid patients and correlates with the initial phase of the disease, (2) in pemphigus vulgaris patients with mucosal involvement during the clinical transition to a mucocutaneous form, (3) in endemic pemphigus foliaceus, underlining its role in disease pathogenesis, and (4) in numerous cases of disease transition associated with an intermolecular diversification of immune response. All these findings could give useful information to better understand autoimmune disease pathogenesis and to design antigen/epitope specific therapeutic approaches. PMID:29719538

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial.

PubMed

Williams, Hywel C; Wojnarowska, Fenella; Kirtschig, Gudula; Mason, James; Godec, Thomas R; Schmidt, Enno; Chalmers, Joanne R; Childs, Margaret; Walton, Shernaz; Harman, Karen; Chapman, Anna; Whitham, Diane; Nunn, Andrew J

2017-04-22

Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3-5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604. Between March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1-26·1) favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening, and fatal events at 52 weeks were 18% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9-30·1), p=0·001. Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term. NIHR Health Technology Assessment Programme. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Decreased interleukin-7 and transforming growth factor-beta1 levels in blister fluids as compared to the respective serum levels in patients with bullous pemphigoid. Opposite behavior of TNF-alpha, interleukin-4 and interleukin-10.

PubMed

Giacalone, B; D'Auria, L; Bonifati, C; Ferraro, C; Riccardi, E; Mussi, A; D'Agosto, G; Cordiali-Fei, P; Ameglio, F

1998-08-01

This study analyzes both the blister fluid (BF) and serum levels of IL-7 and TGF-beta1 in samples from 18 patients affected with bullous pemphigoid (BP). These cytokines clearly present lower concentrations (P<0.001) in BFs than in the sera (1/20 and 1/2, respectively). In contrast, TNF-alpha, IL-10 and IL-4 present increased amounts in BFs that were 12, 12 and 17-fold, respectively. Eighteen sera (and 10 suction BF) from normal individuals were also employed as control. Normal sera presented significantly lower serum IL-7 concentrations than BP, while no significant TGF-beta1 variations were observed between normal and pathologic serum samples. In addition, the serum levels detected in BP patients were significantly correlated with disease intensity (r=0.64, P=0.003, evaluated as the number of blisters/erosions for each patient) as well as with the peripheral B-lymphocyte counts (r=0.80, P<0.001) and antibodies directed against the basement membrane zone (r=0.65, P<0.005). Although a clear explanation of this phenomenon is lacking, the data presented in this report agree with a strong decrease of IL-7 production at the local level (keratinocyte is known to produce IL-7 and the latter is known to be down-regulated by IL-10, and in other models also by TGF-beta1 and IL-4, whose levels are elevated in BP BFs) as opposed to an increased peripheral release of the same modulator. The IL-7 reduction may have a biological relevance in controlling a chronic, progressive disease.

Pathophysiology of Autoimmune Bullous Diseases: Nature Versus Nurture.

PubMed

Patel, Forum; Wilken, Reason; Patel, Falin B; Sultani, Hawa; Bustos, Itzel; Duong, Christopher; Zone, John J; Raychaudhuri, Siba P; Maverakis, Emanual

2017-01-01

Pemphigus and pemphigoid are the prototypical immunobullous diseases. Although it has been well established that they are caused by deposition of autoreactive antibodies directed against adherence proteins within the skin, the specific genetic and environmental factors leading to development of these diseases continue to be an area of investigation. Herein, we discuss several of the potential environmental triggers that may induce patients to develop immunobullous diseases including medications, viral infections, UV exposure or other radiation injury and dietary factors. In addition, the potential genetic and immunologic mechanisms contributing to the pathogenesis of pemphigus and pemphigoid will be reviewed. The multifactorial nature of these diseases contributes to their complexity and highlights the importance of a detailed personal and family history when caring for these patients.

Pathophysiology of Autoimmune Bullous Diseases: Nature Versus Nurture

PubMed Central

Patel, Forum; Wilken, Reason; Patel, Falin B; Sultani, Hawa; Bustos, Itzel; Duong, Christopher; Zone, John J; Raychaudhuri, Siba P; Maverakis, Emanual

2017-01-01

Pemphigus and pemphigoid are the prototypical immunobullous diseases. Although it has been well established that they are caused by deposition of autoreactive antibodies directed against adherence proteins within the skin, the specific genetic and environmental factors leading to development of these diseases continue to be an area of investigation. Herein, we discuss several of the potential environmental triggers that may induce patients to develop immunobullous diseases including medications, viral infections, UV exposure or other radiation injury and dietary factors. In addition, the potential genetic and immunologic mechanisms contributing to the pathogenesis of pemphigus and pemphigoid will be reviewed. The multifactorial nature of these diseases contributes to their complexity and highlights the importance of a detailed personal and family history when caring for these patients. PMID:28584368

Use of Epidermolysis Bullosa Biomarkers in Models of Vesicant Injury

DTIC Science & Technology

2006-09-01

on an epithelial cell “scatter factor ,” which was termed ladsin. This molecule is actually the same as laminin-332 and facilitates epithelial tumor ...blistering diseases, such as bullous pemphigoid, dermatitis herpetiformis, and pemphigus vulgaris22. Because proteases are likely to be involved in...exposure to cutaneous sulfur mustard (SM). 2. Molecular Studies: Biomarkers of epidermolysis bullosa (BEB), laminin alpha 3, laminin beta 3 and

The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury

PubMed Central

Fang, Hui; Zhang, Yang; Li, Ning; Wang, Gang; Liu, Zhi

2018-01-01

Bullous pemphigoid (BP) is an autoimmune and inflammatory skin disease associated with subepidermal blistering and autoantibodies directed against the hemidesmosomal components BP180 and BP230. Animal models of BP were developed by passively transferring anti-BP180 IgG into mice, which recapitulates the key features of human BP. By using these in vivo model systems, key cellular and molecular events leading to the BP disease phenotype are identified, including binding of pathogenic IgG to its target, complement activation of the classical pathway, mast cell degranulation, and infiltration and activation of neutrophils. Proteinases released by infiltrating neutrophils cleave BP180 and other hemidesmosome-associated proteins, causing DEJ separation. Mast cells and mast cell-derived mediators including inflammatory cytokines and proteases are increased in lesional skin and blister fluids of BP. BP animal model evidence also implicates mast cells in the pathogenesis of BP. However, recent studies questioned the pathogenic role of mast cells in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and epidermolysis bullosa acquisita. This review highlights the current knowledge on BP pathophysiology with a focus on a potential role for mast cells in BP and mast cell-related critical issues needing to be addressed in the future. PMID:29545809

TNF-α -308G/A gene polymorphism in bullous pemphigoid and alopecia areata.

PubMed

Moravvej, Hamideh; Tabatabaei-Panah, Pardis-Sadat; Ebrahimi, Elaheh; Esmaeili, Nafiseh; Ghaderian, Sayyed Mohammad Hossein; Ludwig, Ralf J; Akbarzadeh, Reza

2018-05-11

TNF-α -308G/A polymorphism has been investigated in few studies for an association with susceptibility to bullous pemphigoid (BP) and alopecia areata (AA). Yet, these findings had so far not been independently replicated, and no data on a possible association of TNFα -308G/A polymorphism with these diseases in Iranian population were available. In the present study, a possible effect of TNF-α -308G/A variation on susceptibility to BP or AA disease was evaluated. Genomic DNA was extracted from the blood of the patients with BP and AA as well as control subjects which genotyped for the TNF-α -308 G/A polymorphism. TNF-α gene expression levels were analyzed by real-time RT-PCR. No association was observed between the TNF-α -308 G/A variation and susceptibility to BP or AA diseases in our Iranian cohort. In contrast to AA patients, expression of TNF-α gene was significantly higher in BP patients compared to control group. TNF-α gene was found to be similarly expressed in mutant and wild-type genotypes. TNF-α -308G/A polymorphism is not associated with the risk to develop of BP and AA in our Iranian cohort. Furthermore, this polymorphism is not contributed to altering the levels of gene expression in both diseases.

Cytokine pattern in blister fluid and serum of patients with bullous pemphigoid: relationships with disease intensity.

PubMed

Ameglio, F; D'Auria, L; Bonifati, C; Ferraro, C; Mastroianni, A; Giacalone, B

1998-04-01

Few and contrasting data are available in the literature concerning the levels of various cytokines in blister fluid (BF) and in the serum of patients affected with bullous pemphigoid (BP). Using commercially available ELISA kits, this study reports the levels of 11 cytokines detected both in BF and sera of 15 BP patients and compares them with those of 15 control subjects' sera. Generally, no significant differences were observed in BP and control sera. In contrast, interleukin (IL) 1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) showed increased BF levels as compared with BP sera. Two cytokines, IL-11 and IL-12 did not show significant differences between BP BF and sera, while an opposite behaviour was observed for transforming growth factor beta 1 (TGF-beta 1), whose serum levels were higher than the concentrations in BF. Using the number of lesions of the patients as a possible disease intensity marker, significant correlations were found with the BF levels of IL-1 beta, IL-8, TNF-alpha and, most closely, IL-5. These data may have pathogenetic relevance and suggest the possibility that these biological modulators may be used as a quantitative marker of disease intensity.

Drug-induced bullous pemphigoid in diabetes mellitus patients receiving dipeptidyl peptidase-IV inhibitors plus metformin.

PubMed

Skandalis, K; Spirova, M; Gaitanis, G; Tsartsarakis, A; Bassukas, I D

2012-02-01

Preclinical data and reports of adverse skin reactions in patients treated with dipeptidyl peptidase-IV inhibitors (gliptins) have increased awareness towards skin-targeting side-effects of these anti-hyperglycaemic drugs. Bullous pemphigoid (BP), sometimes drug-induced, is the most commonly acquired autoimmune blistering dermatosis in western countries, typically a disease of the elderly people with significant morbidity and excess mortality. To report the development of BP in five diabetics under gliptin (4 vildagliptin, 1 sitagliptin) plus metformin in fixed-dose drug combinations. From March to August 2010 six out of nine newly diagnosed BP patients in our Department were type 2 diabetics. Five of them were on gliptin plus metformin (three different trade preparations) for 2-13 months prior to BP onset. In all cases BP was controlled after withdrawal of the suspected medication and relatively mild therapeutic interventions. In two cases the eliciting role of the preceding treatment is supported by evidence at the level 'probable/likely' according to the WHO-UMC algorithm. This is the first report of drug-induced BP as a group adverse event of the gliptins plus metformin combination therapy for glycaemia control in type 2 diabetes mellitus patients. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Mortality in bullous pemphigoid and prognostic factors in 1st and 3rd year of follow-up in specialized centre in Poland.

PubMed

Kalinska-Bienias, Agnieszka; Lukowska-Smorawska, Katarzyna; Jagielski, Pawel; Kowalewski, Cezary; Wozniak, Katarzyna

2017-11-01

Bullous pemphigoid (BP) is associated with higher mortality and coexisting comorbidities, some of them affecting poor prognosis. The aim of the study was to identify prognostic factors causing greater mortality both in the 1st and 3rd year of follow-up and to determine the 1-, 2-, 3-year mortality rates, standardized mortality ratio (SMR) in Polish BP patients. All patients with BP (a cohort of 205 patients, mean age 76.2 years) diagnosed between 5 January 2000 and 10 December 2013 in a referral unit for autoimmune bullous diseases at the university hospital in Poland were included retrospectively. Mortality data were obtained from the Centre for Document Personalization at the Minister of Interior and Administration. Our original observation was that prednisone in moderate dose (0.5 mg kg -1 ) in monotherapy was an independent risk factor of fatal prognosis in the 1st year of follow-up, assessed using multivariate analysis. We confirmed the strong correlation between neurological diseases and greater mortality. Both in the 1st and 3rd year of follow-up, dementia and Parkinson disease resulted in increased mortality. We also found that arrhythmias significantly increased mortality in the 1st and 3rd year of follow-up. The prognostic factors in BP changed over time of follow-up. In the 3rd year of observation, the age above 77, longer hospitalization and BP severity were associated with greater mortality. We observed poorer prognosis in BP patients than age-matched general Polish population. The 1-, 2-, 3-year mortality rates were 22.4, 31.2, 39.5% and SMR was 3.8 (95% CI 3.4-3.7).

Anti-Type VII Collagen Antibodies Are Identified in a Subpopulation of Bullous Pemphigoid Patients With Relapse

PubMed Central

Giusti, Delphine; Gatouillat, Grégory; Le Jan, Sébastien; Plée, Julie; Bernard, Philippe; Antonicelli, Frank; Pham, Bach-Nga

2018-01-01

Bullous pemphigoid (BP) is an autoimmune bullous skin disease characterized by anti-BP180 and anti-BP230 autoantibodies (AAbs). Mucous membrane involvement is an uncommon clinical feature of BP which may evoke epidermolysis bullosa acquisita, another skin autoimmune disease characterized by anti-type VII collagen AAbs. We therefore evaluated the presence of anti-type VII collagen AAbs in the serum of BP patients with and without mucosal lesions at time of diagnosis and under therapy. Anti-BP180, anti-BP230, and anti-type VII collagen AAbs were measured by ELISA in the serum of unselected patients fulfilling clinical and histo/immunopathological BP criteria at baseline (n = 71) and at time of relapse (n = 24). At baseline, anti-type VII collagen AAbs were detected in 2 out of 24 patients with BP presenting with mucosal involvement, but not in patients without mucosal lesions (n = 47). At the time of relapse, 10 out of 24 BP patients either displayed a significant induction or increase of concentrations of anti-type VII collagen AAbs (P < 0.01), independently of mucosal involvement. Those 10 relapsing BP patients were also characterized by a sustained high concentration of anti-BP180 AAb, whereas the serum anti-BP230 AAb concentrations did not vary in BP patients with relapse according to the presence of anti-type VII collagen AAbs. Thus, our study showed that anti-type VII collagen along with anti-BP180 AAbs detection stratified BP patients at time of relapse, illustrating a still dysregulated immune response that could reflect a potential epitope spreading mechanism in those BP patients. PMID:29619029

Evidence for a role of eosinophils in blister formation in bullous pemphigoid.

PubMed

de Graauw, E; Sitaru, C; Horn, M; Borradori, L; Yousefi, S; Simon, H-U; Simon, D

2017-07-01

Bullous pemphigoid (BP) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue-bound and circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. Although eosinophils and their toxic mediators are found abundantly in BP lesions, their role in blister formation has remained unclear. To investigate the role of eosinophils in the pathogenesis of BP with a specific focus on blister formation and to define conditions inducing dermal-epidermal separation (DES). In an ex vivo human model of BP, normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of BP autoantibodies, brefeldin A, diphenyleneiodonium, DNase or blocking F(ab') 2 fragments to CD16, CD18, CD32 and CD64. Dermal-epidermal separation was assessed by light microscopy studies and quantified using Fiji software. Following activation with IL-5 and in the presence of BP autoantibodies, eosinophils induced separation along the dermal-epidermal junction of ex vivo skin. Dermal-epidermal separation was significantly reduced by blocking any of the following: Fcγ receptor binding (P = 0.048), eosinophil adhesion (P = 0.046), reactive oxygen species (ROS) production (P = 0.002), degranulation (P < 0.0001) or eosinophil extracellular trap (EET) formation (P = 0.048). Our results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodies. Dermal-epidermal separation by IL-5-activated eosinophils depends on adhesion and Fcγ receptor activation, requires elevated ROS production and degranulation and involves EET formation. Thus, targeting eosinophils may be a promising therapeutic approach for BP. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High Index Values of Enzyme-Linked Immunosorbent Assay for BP180 at Baseline Predict Relapse in Patients With Bullous Pemphigoid

PubMed Central

Koga, Hiroshi; Teye, Kwesi; Ishii, Norito; Ohata, Chika; Nakama, Takekuni

2018-01-01

Bullous pemphigoid (BP) presenting with erythema plaques and tense blisters is the most frequent autoimmune bullous disease. Immunologically, BP is characterized by the presence of circulating anti-epidermal basement membrane zone (BMZ) antibodies. The autoantigens in BMZs targeted by patient's antibodies are mainly BP180 (type XVII collagen) and BP230. Previous reports have indicated that IgG to the immunodominant region of BP180 in BP, 16th non-collagenous domain (NC16A), and anti-BP180NC16A IgE are related to disease activity. In the cytokine profile, serum levels of IL-6, TNF-α, IL-15, and CCL18 were associated with the severity or activity of the disease. Blood eosinophilia is seen frequently, especially in severe cases. These biomarkers are helpful to evaluate efficacy of treatment and disease severity. Due to the high frequency of disease relapse, prediction of relapse at initiation of treatment (baseline) must be beneficial for clinicians. Therefore, we evaluated biomarkers anti-BP180 IgG (BP180 ELISA), anti-BP230 IgG (BP230 ELISA), peripheral eosinophils, and serum IgE at baseline between BP patients with (n = 16) and without (n = 31) relapse. We found significantly higher index values of BP180 ELISA in the relapse group, whereas no significant difference was found in BP230 ELISA, peripheral eosinophils, and serum IgE. This study indicated that a high index value of BP180 ELISA (cutoff value, 53.09 U/mL; sensitivity, 81.3%; specificity, 48.4%) at baseline may predict relapse in patients with BP. This may help clinicians treating BP patients in decision-making regarding duration and intensity of treatment. PMID:29868591

Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid

PubMed Central

Chen, Ruoyan; Ning, Gang; Zhao, Ming-Lang; Fleming, Matthew G.; Diaz, Luis A.; Werb, Zena; Liu, Zhi

2001-01-01

Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with an IgG autoimmune response to the hemidesmosomal protein BP180. Passive transfer of antibodies to the murine BP180 (mBP180) ectodomain triggers a blistering skin disease in mice that depends on complement activation and neutrophil infiltration and closely mimics human BP. In the present study, we show that mast cells (MCs) play a crucial role in experimental BP. Wild-type mice injected intradermally with pathogenic anti-mBP180 IgG exhibited extensive MC degranulation in skin, which preceded neutrophil infiltration and subsequent subepidermal blistering. In contrast, mice genetically deficient in MCs or MC-sufficient mice pretreated with an inhibitor of MC degranulation failed to develop BP. Further, MC-deficient mice reconstituted in skin with MCs became susceptible to experimental BP. Despite the activation of complement to yield C3a and C5a, in the absence of MCs, accumulation of neutrophils at the injection site was blunted. The lack of response due to MC deficiency was overcome by intradermal administration of a neutrophil chemoattractant, IL-8, or by reconstitution of the injection sites with neutrophils. These findings provide the first direct evidence to our knowledge that MCs play an essential role in neutrophil recruitment during subepidermal blister formation in experimental BP. PMID:11602622

High levels of interleukin-8, soluble CD4 and soluble CD8 in bullous pemphigoid blister fluid. The relationship between local cytokine production and lesional T-cell activities.

PubMed

Sun, C C; Wu, J; Wong, T T; Wang, L F; Chuan, M T

2000-12-01

Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with autoantibodies that recognize hemidesmosomal proteins. In addition to autoantibodies, the cell-mediated immune reaction is considered to play an important part in blister formation. Objectives To investigate some T-cell activation markers and inflammatory cytokines in the blister fluid and sera of patients with BP. We measured soluble CD4 (sCD4) and soluble CD8 (sCD8), which have been, respectively, associated with CD4 and CD8 T-cell activation. Enzyme-linked immunosorbent assays were also used to quantify the production of the leucocyte chemoattractant interleukin (IL) -8 and of the cytokines IL-1alpha, IL-1beta, IL-6, IL-10 and tumour necrosis factor-alpha in the blister fluid and sera of 11 patients with BP. The mean +/- SD level of sCD4 in patients' blisters (42.4 +/- 25.0 units mL-1) was significantly elevated (P < 0.005) compared with that in their sera (11.2 +/- 8.9) and that in the suction blisters of 10 healthy people (11.4 +/- 5.4; P < 0.005). Mean +/- SD IL-8 concentrations in BP blisters (4683.6 +/- 3878.1 pg mL-1) were much higher than those in their sera (17.1 +/- 18.9; P < 0.001), and were very significantly elevated (P < 0.005) in comparison with those in suction blisters of healthy persons (512 +/- 292). sCD4 levels in BP blisters were inversely related to IL-10 levels (P = 0. 03, r2 = 0.85), IL-8 levels were positively related to sCD8 levels (P = 0.01, r2 = 0.54), and IL-1beta levels were positively related to sCD8 concentrations (P < 0.005, r2 = 0.65). The correlations suggest that there is a delicately orchestrated network of cytokines and cell-mediated immunity operating in BP blisters.

Modified osteo-odonto-keratoprosthesis for treatment of corneal blindness: long-term anatomical and functional outcomes in 181 cases.

PubMed

Falcinelli, Giancarlo; Falsini, Benedetto; Taloni, Maurizio; Colliardo, Paolo; Falcinelli, Giovanni

2005-10-01

To evaluate long-term anatomical and functional outcomes of a modified osteo-odonto-keratoprosthesis (OOKP) technique for treatment of corneal blindness from various etiologies. Two-hundred three patients (224 eyes) underwent modified OOKP surgery between 1973 and 1999. Of the original cohort, 181 patients (98 men and 83 women; mean [SD], age 54.3 [15] years) in whom a standardized 2-step surgical procedure was performed were included in the study. Preoperative diagnoses were dry eye (n = 70) due to ocular pemphigoid (n = 39), Sjögren syndrome (n = 11), trachoma (n = 8), Lyell syndrome (n = 6), Stevens-Johnson syndrome (n = 4), and graft-vs-host disease (n = 1) and congenital lid coloboma (n = 1), severe corneal burns (n = 68), bullous keratopathy (n = 13), keratitis sequelae (n = 15), and bullous keratopathy secondary to antiglaucoma surgery (n = 15). Several innovations were made to the original Strampelli technique. Median follow-up duration was 12 years (range, 1-25 years). Anatomical complications leading to OOKP loss were found in 11 (6.07%) of 181 patients. Survival analysis estimated that 18 years after surgery, the probability of retaining an intact OOKP was 85% (95% confidence interval, 79.3%-90.7%). Pooling patient groups, mean (SD) best postoperative visual acuity was 0.76 (0.34). Mean (SD) final acuity at the end of follow-up declined slightly (0.69 [0.39]) but significantly (P<.01). In individual diagnostic groups, mean acuity decline reached statistical significance (P<.05) only in the pemphigoid (1 line), trachoma (1 line), and bullous keratopathy secondary to antiglaucoma surgery (2 lines) groups. Survival analysis estimated that 18 years after surgery, the probability of retaining best postoperative visual acuity (within 2 lines) was mean (SD) 55.5% (12.9%). Modified OOKP surgery for corneal blindness of different etiologies may provide, in the long-term, anatomically stable corneal prosthesis as well as an effective, rehabilitating recovery in visual acuity.

Measuring of quality of life in autoimmune blistering disorders in Poland. Validation of disease - specific Autoimmune Bullous Disease Quality of Life (ABQOL) and the Treatment Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires.

PubMed

Kalinska-Bienias, Agnieszka; Jakubowska, Beata; Kowalewski, Cezary; Murrell, Dedee F; Wozniak, Katarzyna

2017-03-01

Autoimmune bullous dermatoses (AIBD) are rare, severe diseases resulting from some antibodies activity against the different adhesion structures within the skin and/or mucosa. Few studies investigated quality of life (QOL) in AIBD by generic and dermatology-specific instruments, all reporting strong impact on QOL. Recently, disease-specific measurement tools have been developed: Autoimmune Bullous Disease Quality of Life (ABQOL) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires. The aim of this study was to test the reliability and validity of ABQOL and TABQOL by developing the first foreign language versions and to evaluate ABQOL and TABQOL in Polish patients. The study enrolled 80 patients from the tertiary referral center for AIBD at the outpatient clinic or on admission to the hospital. Sixty six patients completed the 17-item questionnaires of each ABQOL and TABQOL at day 0 and after 5-7 days. Both questionnaires were translated into Polish according to protocol. The internal consistency and test-retest reliability were high (Cronbach α=0.95 for ABQOL, α=0.87 for TABQOL), (R=0.98 for ABQOL, R=0.86 for TABQOL). In convergent validity, the correlation of ABQOL and TABQOL was strong (R=0.81), but low with objective disease activity scales. The strongest impact of AIBD on QOL has been observed in flares and in patients with the onset below 70 years of age. The patients with bullous pemphigoid had the highest QOL compared to other AIBD patients. The ABQOL and TABQOL are reliable and valid instruments for the assessment of QOL in AIBD. Copyright © 2016 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Interleukin-16 expression and release in bullous pemphigoid

PubMed Central

FREZZOLINI, A; CIANCHINI, G; RUFFELLI, M; CADONI, S; PUDDU, P; DE PITÀ, O

2004-01-01

Cutaneous infiltration of activated CD4+ T cells and eosinophils is an early event in blister formation during bullous pemphigoid (BP), suggesting that the trafficking of circulating leucocytes through the sites of inflammation, their activation and cytokine release is crucial in the pathogenesis of the disease. IL-16 is a major chemotactic factor able to recruit CD4+ cells in the skin during inflammation and to induce the expression of functional high-affinity interleukin (IL)-2 receptors, thus contributing to cellular activation and proliferation. We performed a study in order to evaluate the presence of IL-16 in skin samples and sera and blister fluids of patients affected with BP in active phase of the disease (n = 39), compared with healthy donors studied as control group. Ten patients were also evaluated before and after steroid therapy. Our results demonstrated that IL-16 was expressed strongly by keratinocytes and by dermal infiltrating CD4+ T lymphocytes in lesional skin of BP patients. High levels of IL-16 were detected in sera and blisters of BP, significantly higher in respect to healthy donors. When patients were investigated for the presence of eosinophil cationic protein (ECP) and soluble CD30 (sCD30) to reveal signs of eosinophils and Th2-cells activation, we found a positive correlation between IL-16 serum levels and both ECP and sCD30, suggesting that IL-16 is involved in Th2 lymphocytes and eosinophils recruitment during BP. PMID:15320912

Management of cutaneous disorders related to inflammatory bowel disease

PubMed Central

Pellicer, Zaira; Santiago, Jesus Manuel; Rodriguez, Alejandro; Alonso, Vicent; Antón, Rosario; Bosca, Marta Maia

2012-01-01

Almost one-third of patients with inflammatory bowel disease (IBD) develop skin lesions. Cutaneous disorders associated with IBD may be divided into 5 groups based on the nature of the association: specific manifestations (orofacial and metastatic IBD), reactive disorders (erythema nodosum, pyoderma gangrenosum, pyodermatitis-pyostomatitis vegetans, Sweet’s syndrome and cutaneous polyarteritis nodosa), miscellaneous (epidermolysis bullosa acquisita, bullous pemphigoid, linear IgA bullous disease, squamous cell carcinoma-Bowen’s disease, hidradenitis suppurativa, secondary amyloidosis and psoriasis), manifestations secondary to malnutrition and malabsorption (zinc, vitamins and iron deficiency), and manifestations secondary to drug therapy (salicylates, immunosupressors, biological agents, antibiotics and steroids). Treatment should be individualized and directed to treating the underlying IBD as well as the specific dermatologic condition. The aim of this review includes the description of clinical manifestations, course, work-up and, most importantly, management of these disorders, providing an assessment of the literature on the topic. PMID:24713996

Photo-induced toxic epidermal necrolysis caused by clobazam.

PubMed

Redondo, P; Vicente, J; España, A; Subira, M L; De Felipe, I; Quintanilla, E

1996-12-01

Toxic epidermal necrolysis (TEN) is a life-threatening disease, the pathogenesis of which remains largely unknown. We describe a 23-year-old woman under treatment with clobazam who developed lesions of TEN in light-exposed areas. Patch and photopatch tests with clobazam were negative. The cellular phenotype and cytokines were studied in blister fluid. The cellular infiltrate was composed mainly of T lymphocytes with a predominant cytotoxic phenotype. There was an increase in the level of tumour necrosis factor (TNF)-alpha in blister fluid compared with the control (a patient with bullous pemphigoid).

Bullous Scabies.

PubMed

Luo, Di-Qing; Huang, Mei-Xing; Liu, Juan-Hua; Tang, Wen; Zhao, Yu-Kun; Sarkar, Rashmi

2016-09-07

Scabies is a common contagious cutaneous disease and usually affects the young, characterized by polymorphous lesions that may present as burrows, pruritic papules, and inflammatory nodules. Bullous scabies (BS) is its rather rare subtype, mimicking bullous pemphigoid. We report a 15-year-old Chinese boy presenting with 1-month history of pruritic bullae on his penile skin, showing poor response to both topical steroids and systemic antihistamines, but cured by sulfur ointment alone. No recurrence occurred in the 5 years of follow-up. We also reviewed the published cases. Up to date, 44 cases, including the present, have been reported. Of them, 30 were male and 14 were female. The age range was from 1 to 89 years old, with a median age of 70.6 years. The bullous lesions may involve the arms, legs, trunk, genitals, feet, buttocks, thighs, neck, inguinal folds, and may even be generalized. Trunk and extremities are the most common involved locations. Facial or mucosa involvement had never been reported. The histological findings present as a subepidermal split with variable inflammatory infiltrate predominantly neutrophils, and eosinophilic spongiosis, or both. Eighteen of 32 patients showed positive deposition of linear-granular IgG or complement 3 alone or in various combinations, and five of 24 patients revealed circulating IgG. All the 40 cases with therapeutic details were cured by antiscabietic remedy. BS always involves the trunk and extremities. It has a predilection for elderlies and males. The treatments for BS are similar to those of classical scabies. © The American Society of Tropical Medicine and Hygiene.

Bullous Scabies

PubMed Central

Luo, Di-Qing; Huang, Mei-Xing; Liu, Juan-Hua; Tang, Wen; Zhao, Yu-Kun; Sarkar, Rashmi

2016-01-01

Scabies is a common contagious cutaneous disease and usually affects the young, characterized by polymorphous lesions that may present as burrows, pruritic papules, and inflammatory nodules. Bullous scabies (BS) is its rather rare subtype, mimicking bullous pemphigoid. We report a 15-year-old Chinese boy presenting with 1-month history of pruritic bullae on his penile skin, showing poor response to both topical steroids and systemic antihistamines, but cured by sulfur ointment alone. No recurrence occurred in the 5 years of follow-up. We also reviewed the published cases. Up to date, 44 cases, including the present, have been reported. Of them, 30 were male and 14 were female. The age range was from 1 to 89 years old, with a median age of 70.6 years. The bullous lesions may involve the arms, legs, trunk, genitals, feet, buttocks, thighs, neck, inguinal folds, and may even be generalized. Trunk and extremities are the most common involved locations. Facial or mucosa involvement had never been reported. The histological findings present as a subepidermal split with variable inflammatory infiltrate predominantly neutrophils, and eosinophilic spongiosis, or both. Eighteen of 32 patients showed positive deposition of linear-granular IgG or complement 3 alone or in various combinations, and five of 24 patients revealed circulating IgG. All the 40 cases with therapeutic details were cured by antiscabietic remedy. BS always involves the trunk and extremities. It has a predilection for elderlies and males. The treatments for BS are similar to those of classical scabies. PMID:27402514

Dipeptidyl peptidase-4 inhibitors-associated bullous pemphigoid: a retrospective study of 168 pemphigoid and 9,304 diabetes mellitus cases.

PubMed

Kawaguchi, Yohei; Shimauchi, Risa; Nishibori, Nobuhiro; Kawashima, Kiyohito; Oshitani, So; Fujiya, Atsushi; Shibata, Taiga; Ohashi, Norimi; Izumi, Kentaro; Nishie, Wataru; Shimizu, Hiroshi; Arima, Hiroshi; Sobajima, Hiroshi

2018-06-19

Bullous pemphigoid (BP) may be drug-induced. This study evaluated the relation between BP and dipeptidyl peptidase-4 inhibitors (DPP4Is). We recruited patients diagnosed with BP at Ogaki Municipal Hospital from December 1, 2009 through December 31, 2017. We retrospectively collected data from medical records and divided patients into two groups based on whether they received DPP4Is. Additionally, we determined the incidence of BP in patients who were first prescribed DPP4Is at our hospital during the study period. Of 168 patients diagnosed with BP, 133 (79.1%) were positive for anti-BP180NC16a antibody. Thirty-two (19.0%) patients had been prescribed a DPP4I, 21 of whom (65.6%) were positive for anti-BP180NC16a antibody; this rate was lower than that in patients not receiving a DPP4I (82.3%) (p = 0.0360). Sixteen patients with type 2 diabetes mellitus (T2DM) had not been prescribed a DPP4I; only one (6.3%) was positive for anti-BP180NC16a antibody (p = 0.0339). During the study period, 9304 patients were prescribed DPP4Is, eight of whom developed BP; six (75.0%) had non-inflammatory BP, and five of the six (83.3%) were negative for anti-BP180NC16a antibody. The positive rate of anti-BP180NC16a antibody was lower in BP patients with DPP4I than without DPP4I, regardless of T2DM. The antibody titer was low in both the overall and T2DM populations. The prevalence of BP in 9304 patients receiving DPP4Is was 0.0859%, which is higher than that in the general population. Since DPP4Is are common diabetes treatments, we must be aware of the risk of BP. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Up-regulation of CCL11 and CCL26 is associated with activated eosinophils in bullous pemphigoid

PubMed Central

Günther, C; Wozel, G; Meurer, M; Pfeiffer, C

2011-01-01

Eosinophils contribute to the pathogenesis of bullous pemphigoid (BP) by secretion of proinflammatory cytokines and proteases. Trafficking of eosinophils into tissue in animal models and asthma depends on interleukin-5 and a family of chemokines named eotaxins, comprising CCL11, CCL24 and CCL26. Up-regulation of CCL11 has been described in BP, but the expression of the other two members of the eotaxin-family, CCL24 and CCL26, has not been investigated. In addition to these chemokines, expression of adhesion molecules associated with eosinophil migration to the skin should be analysed. We demonstrate that similar to CCL11, the concentration of CCL26 was up-regulated in serum and blister fluid of BP patients. In contrast, the concentration of CCL24 was not elevated in sera and blister fluid of the same BP patients. In lesional skin, CCL11 and CCL26 were detected in epidermis and dermis by immunohistochemistry. In contrast to CCL11, CCL26 was expressed strongly by endothelial cells. In line with these findings, eosinophils represented the dominating cell population in BP lesional skin outnumbering other leucocytes. The percentage of eosinophils expressing very late antigen (VLA): VLA-4 (CD49d) and CD11c correlated with their quantity in tissue. Macrophage antigen (MAC)-1 (CD11b/CD18) was expressed constitutively by tissue eosinophils. In conclusion, these data link the up-regulation of the eosinophil chemotactic factor CCL26 in BP to the lesional accumulation of activated eosinophils in the skin. Thereby they broaden the understanding of BP pathogenesis and might indicate new options for therapeutic intervention. PMID:21985360

Successful treatment by double-filtration plasmapheresis of a patient with bullous pemphigoid: effects in vivo on transcripts of several genes for chemokines and cytokines in peripheral blood mononuclear cells.

PubMed

Hatano, Y; Katagiri, K; Arakawa, S; Umeki, T; Takayasu, S; Fujiwara, S

2003-03-01

The involvement of various cytokines and chemokines has been reported in the pathogenesis of bullous pemphigoid (BP). Double-filtration plasmapheresis (DFPP) is an effective treatment for BP but the mechanism of action remains unclear. Using semiquantitative reverse transcription-polymerase chain reaction, we examined levels of transcripts for various cytokines and chemokines in freshly isolated peripheral blood mononuclear cells in a patient with BP before and after DFPP treatment. DFPP was performed four times. Relative levels of transcripts for interleukin (IL)-8, macrophage inflammatory protein (MIP)-1alpha and IL-5, and the ratio of relative levels of transcripts for IL-4 and interferon (IFN)-gamma, were higher, before treatment, than in healthy controls, and decreased when the extent of the lesions was reduced. Relative levels of transcripts for tumour necrosis factor (TNF)-alpha and IL-4 also decreased with regression of lesions, although they were similar to or lower than the corresponding levels in healthy individuals. When eruptions recurred, relative levels of transcripts for IL-8, MIP-1alpha, RANTES (regulated upon activation normal T cell expressed and secreted), IL-2, IFN-gamma and TNF-alpha were very much higher than those prior to the recurrence, while relative levels of mRNAs for IL-4 and IL-5 did not increase. Relative levels of transcripts for IL-8, MIP-1alpha, TNF-alpha and IL-2 were lower at the end of each individual DFPP and after the four treatments than at the beginning of treatment. Our observations suggest that cytokines and chemokines produced in mononuclear cells play important roles in the pathogenesis of BP and that regulation of their expression might be involved in the therapeutic effects of DFPP in BP.

Coagulation activation in autoimmune bullous diseases

PubMed Central

Marzano, A V; Tedeschi, A; Spinelli, D; Fanoni, D; Crosti, C; Cugno, M

2009-01-01

The main autoimmune blistering skin disorders are pemphigus vulgaris (PV) and bullous pemphigoid (BP). They differ in the inflammatory infiltrate, which is more intense in BP. Inflammation is known to activate coagulation in several disorders. Local and systemic activation of coagulation was evaluated in BP and PV. We studied 20 BP patients (10 active and 10 remittent), 23 PV patients (13 active and 10 remittent) and 10 healthy subjects. The coagulation markers prothrombin fragment F1+2 and D-dimer were measured by enzyme-immunoassays in plasma. The presence of tissue factor (TF), the main initiator of blood coagulation, was evaluated immunohistochemically in skin specimens from 10 patients with active PV, 10 patients with active BP and 10 controls. Plasma F1+2 and D-dimer levels were significantly high in active BP (P = 0·001), whereas in active PV the levels were normal. During remission, F1+2 and D-dimer plasma levels were normal in both BP and PV. TF immunoreactivity was found in active BP but neither in active PV nor in normal skin. TF reactivity scores were higher in active BP than in controls or active PV (P = 0·0001). No difference in TF scores was found between active PV and controls. BP is associated with coagulation activation, which is lacking in PV. This suggests that BP but not PV patients have an increased thrombotic risk. The observation that thrombotic complications occur more frequently in BP than in PV further supports this view. PMID:19737228

Bullous pemphigoid and pemphigus vulgaris: correlated behaviour of serum VEGF, sE-selectin and TNF-alpha levels.

PubMed

Ameglio, F; D'Auria, L; Cordiali-Fei, P; Mussi, A; Valenzano, L; D'Agosto, G; Ferraro, C; Bonifati, C; Giacalone, B

1997-01-01

Recently, we reported that soluble E-selectin (sE-selectin), an isoform of the cell membrane E-selectin, an adhesion molecule synthesized only by endothelial cells, is significantly increased in sera of the patients with bullous pemphigoid (PB) or pemphigus vulgaris. A significant correlation was also found between the serum sE-selectin levels and the number of skin lesions, suggesting the possible use of this molecule to gauge disease intensity before therapy. One of the sE-selectin inducers is tumor nerosis factor-alpha (TNF-alpha), that is also able to enhance vascular endothelial growth factor (VEGF), a strong endothelium activator. On the basis of these observations, the present study was conducted to analyze the serum levels of VEGF, sE-selectin, and TNF-alpha in 8 patients with BP (age: 82, range 54-87, 7 males, 1 female) and in 6 patients affected affected with PV (age: 55, range 44-65; 5 males, 1 female) and to verify possible correlations between these variables and the disease activity, In addition, serum sE-selectin levels were measured over time and compared with the serum anti-epithelium antibodies titers. The sE-selectin, VEGF and TNF-alpha levels were measured in the samples by means of commercially available ELISA kit. The same samples were also employed to measure the anti-epithelium antibody titers. Serum VEGF, sE-selectin and TNF-alpha levels were significantly correlated each other (p at least < 0.01). All three variables were also significantly correlated with the number of lesions (p at least < 0.01). Serum VEGF levels were found increased (median = 178 pg/ml, range 37-595) as compared to 28 healthy controls (median = 135 pg/ml, range 18/269, p < 0.05). Also serum TNF-alpha levels were found increased (median = 5.5 pg/ml, range < 0.1-41.0) as compared to 28 healthy controls (median < 0.1 pg/ml, range < 0.1-5.3), p < 0.01). When the patients were observed over time, serum sE-selectin levels highly correlated with the disease intensity in both dermatoses, although with different regression curves. These data further underline the endothelium involvement in these bullous dermatoses and stress the possibility of employing sE-selectin as a non-specific follow-up marker of both BP and PV.

Collagen XVII: A Shared Antigen in Neurodermatological Interactions?

PubMed Central

2013-01-01

Collagen XVII is a nonfibril-forming transmembrane collagen, which functions as both a matrix protein and a cell-surface receptor. It is particularly copious in the skin, where it is known to be a structural component of hemidesmosomes. In addition, collagen XVII has been found to be present in the central nervous system, thus offering an explanation for the statistical association between bullous pemphigoid, in which autoimmunity is directed against dermal collagen XVII, and neurological diseases. In support of the hypothesis that collagen XVII serves as a shared antigen mediating an immune response between skin and brain, research on animal and human tissue, as well as numerous epidemiological and case studies, is presented. PMID:23878581

[Cheyletiella dermatitis: an uncommon cause of vesiculobullous eruption].

PubMed

Tsianakas, P; Polack, B; Pinquier, L; Levy Klotz, B; Prost-Squarcioni, C

2000-10-01

Species of Cheyletiella mites are parasites hosted by dogs, cats and rabbits. In humans, they cause a dermatosis not well known by dermatologists. We report a case of an unusual, purely vesiculobullous eruption due to Cheyletiella blakei acquired from an infected cat. A 76-year-old woman presented a very pruritic eruption of vesicles and bullous lesions located on the trunk and external areas of the arms. Biopsy showed dermoepidermal cleavage and polynuclear infiltrate with prominent eosinophils, consistent with the diagnosis of bullous pemphigoid. We suspected a Cheyletiella dermatitis due to the aspect and distribution of the elementary lesions and the fact that prior to the eruption the patient had acquired a cat that sometimes slept in her bed. The diagnosis was confirmed by a veterinary examination and isolation of Cheyletiella blakei from the cat's skin. The cat was treated successfully with ivermectin, while the household was disinfected with permethrin. A treatment with benzyl benzoate (Ascabiol) resolved all the patient's symptoms. This case is particularly interesting due to the purely vesiculobullous pattern of the rash and by the difficulty and considerable delay of diagnosis. Patients who have recently acquired a cat or dog before developing a pruritic dermatosis may indeed have cheyletiellosis.

Plakins, a versatile family of cytolinkers: roles in skin integrity and in human diseases.

PubMed

Bouameur, Jamal-Eddine; Favre, Bertrand; Borradori, Luca

2014-04-01

The plakin family consists of giant proteins involved in the cross-linking and organization of the cytoskeleton and adhesion complexes. They further modulate several fundamental biological processes, such as cell adhesion, migration, and polarization or signaling pathways. Inherited and acquired defects of plakins in humans and in animal models potentially lead to dramatic manifestations in the skin, striated muscles, and/or nervous system. These observations unequivocally demonstrate the key role of plakins in the maintenance of tissue integrity. Here we review the characteristics of the mammalian plakin members BPAG1 (bullous pemphigoid antigen 1), desmoplakin, plectin, envoplakin, epiplakin, MACF1 (microtubule-actin cross-linking factor 1), and periplakin, highlighting their role in skin homeostasis and diseases.

Epidermolysis bullosa acquisita in a Great Dane.

PubMed

Hill, P B; Boyer, P; Lau, P; Rybnicek, J; Hargreaves, J; Olivry, T

2008-02-01

Autoimmune subepidermal blistering diseases in dogs were all classified as bullous pemphigoid until 1998. Since then, refinements in reagents and immunological techniques have allowed diseases which are histologically similar but which have a different molecular pathogenesis to be described. This report describes the first case of one such disease, epidermolysis bullosa acquisita, to be documented in the UK. The dog presented with a severe blistering and ulcerative disease affecting the oral cavity, pinnae and distal limbs. The diagnosis was confirmed by histopathology and direct and indirect immunofluorescent demonstration of immunoglobulin G reactivity to basement membrane antigens. Treatment with glucocorticoids, azathioprine, colchicine and an intravenous infusion of immunoglobulins resulted in complete resolution. The drugs were discontinued 12 months after the start of treatment and the dog remained in remission.

Macrolides in Chronic Inflammatory Skin Disorders

PubMed Central

Alzolibani, Abdullateef A.; Zedan, Khaled

2012-01-01

Long-term therapy with the macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time, macrolides have been found to have a large number of anti-inflammatory properties in addition to being antimicrobials. These observations provided the rationale for many studies performed to assess the usefulness of macrolides in other inflammatory diseases including skin and hair disorders, such as rosacea, psoriasis, pityriasis rosea, alopecia areata, bullous pemphigoid, and pityriasis lichenoides. This paper summarizes a collection of clinical studies and case reports dealing with the potential benefits of macrolides antibiotics in the treatment of selected dermatoses which have primarily been classified as noninfectious and demonstrating their potential for being disease-modifying agents. PMID:22685371

Bullosis Diabeticorum: A Rare Presentation with Immunoglobulin G (IgG) Deposition Related Vasculopathy. Case Report and Focused Review

PubMed Central

Sonani, Hardik; Salim, Sohail Abdul; Garla, Vishnu V.; Wile, Anna; Palabindala, Venkataraman

2018-01-01

Patient: Male, 42 Final Diagnosis: Bullosis diabeticorum Symptoms: Skin rash Medication: — Clinical Procedure: Debridement Specialty: Metabolic Disorders and Diabetics Objective: Rare co-existance of disease or pathology Background: Bullosis diabeticorum (BD) is a condition characterized by recurrent, spontaneous, and non-inflammatory blistering in patients with poorly controlled diabetes mellitus. While etiopathogenesis remains unclear, roles of neuropathy, vasculopathy and UV light are hypothesized. Most literature reports negative direct and indirect immunofluorescence findings in diabetics with bullous eruptions. Porphyria cutanea tarda, bullous pemphigoid, epidermolysis bullosa, and pseudoporphyria are other differential diagnoses of bullous lesions, and they must be excluded. Case Report: We present a 42-year-old African American male with long standing poorly controlled insulin dependent diabetes mellitus with blisters on his left hand and feet. The blisters were noticed three weeks prior to presentation and, thereafter, rapidly increased in size and spontaneously ruptured. Physical examination revealed a multitude of both roofed and unroofed bullous painless skin lesions. Hematoxylin and eosin (H&E) staining dramatized the dermal-epidermal blistering and re-epithelization process. Direct Immunofluorescence (DIF) was positive for 2 + IgG deposition in the already thickened basement membrane of the capillaries of the superficial vascular plexus. After debridement, his wounds greatly improved with over three months of aggressive wound care. Conclusions: Primary immunologic abnormality likely plays no role in the onset of BD. To date, only one article has reported nonspecific capillary-associated immunoglobulin M and C3. This is the first case of BD with IgG deposition in the superficial capillary basement membrane. Positive findings on DIF suggest vasculopathy. Dermal microangiopathy, secondary to immunologic abnormality, is a possible underlying pathogenesis to bullae formation. Punch biopsy with DIF can be an additional diagnostic modality in the management of such cases. PMID:29332930

Correlation between IL36α and IL17 and Activity of the Disease in Selected Autoimmune Blistering Diseases

PubMed Central

Woźniacka, Anna; Ociepa, Kamila; Waszczykowska, Elżbieta

2017-01-01

Dermatitis herpetiformis (DH), bullous pemphigoid (BP), and pemphigus vulgaris (PV) are autoimmune bullous skin conditions with eosinophilic and neutrophilic infiltrations. While cytokines are crucial for the affinity and activation of different leukocyte cells in the inflammation and blister formation, there are no studies concerning a role of IL-36. The goal of the study was to analyze whether interleukin 36 is involved in pathogenesis of DH, BP, and PV. And the second aim of the study was the estimation of correlation between Il-36 and IL-17 and titers of specific antibodies in these diseases. Expression of IL-36 and IL-17 was detected in serum in all DH, BP, and PV samples. Serum levels of IL-36 and IL-17α were statistically higher in DH, BP, and PV groups as compared to the control group. IL-36α levels were statistically higher in DH patients, as compared to patients with PV and BP. Our results showed that IL-36 may be helpful in the diagnostic and monitoring of the activity of the disease. IL 36 may play a relevant role of enrolling eosinophils and neutrophils in DH, BP, and PV and finally provoke tissue injury. PMID:28611508

Dermatological disease in the older age group: a cross-sectional study in aged care facilities.

PubMed

Deo, Maneka S; Kerse, Ngaire; Vandal, Alain C; Jarrett, Paul

2015-12-23

To estimate the prevalence of dermatological disease in aged care facilities, and the relationship between cognitive or physical disability and significant disease. 2 large aged care facilities in Auckland, New Zealand, each providing low and high level care. All 161 residents of the facilities were invited to participate. The only exclusion criterion was inability to obtain consent from the individual or designated guardian. 88 participants were recruited-66 females (75%), 22 males (25%) with average age 87.1 years (SD 5.5 years). Primary--presence of significant skin disease (defined as that which in the opinion of the investigators needed treatment or was identified as a patient concern) diagnosed clinically on full dermatological examination by a dermatologist or dermatology trainee. Secondary--functional and cognitive status (Rehabilitation Complexity Scale and Abbreviated Mental Test Score). 81.8% were found to have at least one significant condition. The most common disorders were onychomycosis 42 (47.7%), basal cell carcinoma 13 (14.8%), asteototic eczema 11 (12.5%) and squamous cell carcinoma in situ 9 (10.2%). Other findings were invasive squamous cell carcinoma 7 (8%), bullous pemphigoid 2 (2.3%), melanoma 2 (2.3%), lichen sclerosus 2 (2.3%) and carcinoma of the breast 1 (1.1%). Inflammatory disease was more common in those with little physical disability compared with those with serious physical disability (OR 3.69; 95% CI 1.1 to 12.6, p=0.04). No significant association was found between skin disease and cognitive impairment. A high rate of dermatological disease was found. Findings ranged from frequent but not life-threatening conditions (eg, onychomycosis), to those associated with a significant morbidity (eg, eczema, lichen sclerosus and bullous pemphigoid), to potentially life-threatening (eg, squamous cell carcinoma, melanoma and breast cancer). Those with less significant physical impairment were found to be at greater risk of inflammatory dermatoses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Ulcers caused by bullous morphea: successful therapy with N-acetylcysteine and topical wound care.

PubMed

Rosato, E; Veneziano, M L; Di Mario, A; Molinaro, I; Pisarri, S; Salsano, F

2013-01-01

Bullous morphea is an uncommon form of localized scleroderma. The pathogenesis is unknown and treatment of coexistent ulcers is difficult. The pathogenesis of bullae formation in morphea is multifactorial, but reactive oxygen species production appears to play a key role. We report a patient with bullous morphea with long-standing ulcers whom we successfully treated with N-acetylcysteine and topical wound care. N-acetylcysteine, an antioxidant sulfhydryl substance, promotes the healing of ulcers in patients with bullous morphea.

Plakins in striated muscle.

PubMed

Boyer, Justin G; Bernstein, Marija A; Boudreau-Larivière, Céline

2010-03-01

Striated muscle cells contain numerous architectural proteins that contribute to the function of muscle as generators of mechanical force. Among these proteins are crosslinkers belonging to the plakin family, namely plectin, microtubule-actin crosslinking factor (ACF7/MACF1), bullous pemphigoid antigen 1 (Bpag1/dystonin), and desmoplakin. These plakin family members, in particular plectin and Bpag1/dystonin, exist as several isoforms. The domain organization of these plakin variants dictates their subcellular location and the proteins with which they interact. Several studies suggest that plakins exert unique functions within various compartments of the muscle cell including the sarcolemma, the sarcomere, both neuromuscular and myotendinous junctions in skeletal muscle, and the intercalated discs in cardiac muscle. Plakins may also regulate the cellular placement and function of specific organelles, notably the nucleus, mitochondria, Golgi apparatus, and sarcoplasmic reticulum. Here we review and summarize our current knowledge of the function of plakins in striated muscle cells.

Vulvar disease in children: a clinical audit of 130 cases.

PubMed

Fischer, G; Rogers, M

2000-01-01

We evaluated 130 prepubertal girls presenting with a vulvar complaint to determine the spectrum and frequency of conditions seen in this age group. Of the patients, 41 (33%) had atopic or irritant dermatitis, 23 (18%) had lichen sclerosus, 21 (17%) had psoriasis, 15 (12%) had vulvar lesions, most often hemangiomas and nevi, and 13 (10%) had streptococcal vulvovaginitis. Diagnoses less frequently seen were staphylococcal folliculitis (four patients), labial fusion (three patients), genital warts (two patients), molluscum contagiosum of the vulva only (one patient), vulvar bullous pemphigoid (two patients), scabies nodules (one patient), erythema annulare centrifugum (one patient), tinea (two patients), and vitiligo (one patient). We also encountered vulvar presentations of systemic diseases (varicella, staphylococcal scalded skin syndrome, and Henoch-Schönlein purpura, all one patient each). We did not see candidal vulvovaginitis in this age group nor did we encounter bacterial infection with pathogens other than Staphylococcus aureus and S. pyogenes.

Bullous impetigo caused by Streptococcus salivarius: a case report.

PubMed Central

Brook, I

1980-01-01

A 19-month-old child presented with bullous impetigo around the perineal region, penis, and left foot. Streptococcus salivarius was the only isolate recovered from the lesions. The child was treated with parenteral penicillin, debridement of the bulli, and local application of silver sulphadiazine cream. This case of bullous impetigo illustrates another aspect of the pathogenicity of Strep. salivarius. Images Fig. 1 Fig. 2 PMID:7002959

Pregnant women have increased incidence of IgE autoantibodies reactive with the skin and placental antigen BP180 (type XVII collagen)

PubMed Central

Noe, Megan H.; Messingham, Kelly A.N.; Brandt, Debra S.; Andrews, Janet I.; Fairley, Janet A.

2016-01-01

BP180 (type XVII collagen) is a transmembrane protein expressed in a variety of cell types. It is also the target of autoantibodies in cutaneous autoimmune disease including bullous pemphigoid and pemphigoid gestationis, a disease unique to pregnancy. The purpose of this study was to determine the prevalence and specificity of cutaneous autoantibodies in a cohort of pregnant women. De-identified sera were collected from pregnant women (n = 299) and from non-pregnant controls (n = 134). Sera were analyzed by ELISA for the presence of IgG and IgE autoantibodies directed against several cutaneous autoantigens. IgE antibodies against the NC16A domain of BP180 were detected in 7.7% of pregnant women, compared to 2.2% of healthy controls (p = 0.01). No increase in total or cutaneous autoantigen specific IgG was seen. Total serum IgE was within the normal range. Full-length BP180 was detected by western immunoblot in epidermal, keratinocyte, placental and cytotrophoblast (CTB) cell lysates. Furthermore, flow cytometry and indirect immunofluorescence confirmed the expression of BP180 on the surface of cultured CTBs. Finally, it was demonstrated that IgE antibodies in the pregnancy sera labeled not only cultured CTBs, but also the placental amnion and cutaneous basement membrane zone using indirect immunofluorescence. We conclude that some pregnant women develop antibodies specific for BP180, and that these autoantibodies are capable of binding both CTB and the placental amnion, potentially affecting placental function. PMID:20471095

Research Techniques Made Simple: Mouse Models of Autoimmune Blistering Diseases.

PubMed

Pollmann, Robert; Eming, Rüdiger

2017-01-01

Autoimmune blistering diseases are examples of autoantibody-mediated, organ-specific autoimmune disorders. Based on a genetic susceptibility, such as a strong HLA-class II association, as yet unknown triggering factors induce the formation of circulating and tissue-bound autoantibodies that are mainly directed against adhesion structures of the skin and mucous membranes. Compared with other autoimmune diseases, especially systemic disorders, the pathogenicity of autoimmune blistering diseases is relatively well described. Several animal models of autoimmune blistering diseases have been established that helped to uncover the immunological and molecular mechanisms underlying the blistering phenotypes. Each in vivo model focuses on specific aspects of the autoimmune cascade, from loss of immunological tolerance on the level of T and B cells to the pathogenic effects of autoantibodies upon binding to their target autoantigen. We discuss current mouse models of autoimmune blistering diseases, including models of pemphigus vulgaris, bullous pemphigoid, epidermolysis bullosa acquisita, and dermatitis herpetiformis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Diagnostic performance of the "MESACUP anti-Skin profile TEST".

PubMed

Horváth, Orsolya N; Varga, Rita; Kaneda, Makoto; Schmidt, Enno; Ruzicka, Thomas; Sárdy, Miklós

2016-01-01

The "MESACUP anti-Skin profile TEST" is a new, commercially available ELISA kit to detect circulating IgG autoantibodies against desmoglein 1, desmoglein 3, BP180, BP230, and type VII collagen, both simultaneously and more rapidly than previous assays. The aim of this study was to evaluate the diagnostic accuracy of this kit for the diagnosis of pemphigus foliaceus, pemphigus vulgaris, bullous pemphigoid and epidermolysis bullosa acquisita. Dual-centre retrospective study in which 138 patients with autoimmune blistering diseases were compared to 40 controls Using the MESACUP anti-Skin profile TEST, both sensitivities and specificities for desmoglein 1, desmoglein 3, BP180, BP230, and type VII collagen autoantibodies were similar to those obtained using previous, specific ELISA systems and 88% of the results were concordant without any significant difference. The MESACUP anti-Skin profile TEST had a similar performance to previously produced ELISA systems. The novel kit can be used for rapid diagnosis of most common autoimmune blistering diseases and is especially suitable for identifying overlapping disorders.

From HSV infection to erythema multiforme through autoimmune crossreactivity.

PubMed

Lucchese, Alberta

2018-06-01

Scientific and clinical data indicate that human herpes simplex virus 1 (HSV1) and, at a lesser extent, human herpes simplex virus 2 (HSV2) are factor(s) implicated in the development of erythema multiforme (EM). With a focus on oral EM, the present structured review of proteomic and epitope databases searched for the molecular basis that might link HSV1 and HSV2 infections to EM. It was found that a high number of peptides are shared between the two HSVs and human proteins related to the oral mucosa. Moreover, a great number of the shared peptides are also present in epitopes that have been experimentally validated as immunopositive in the human host. The results suggest the involvement of HSV infections in the induction of oral EM via a mechanism of autoimmune cross-reactivity and, in particular, highlight a potential major role for 180kDa bullous pemphigoid antigen and HSV1 infection in the genesis of crossreactions potentially conducive to EM. Copyright © 2018 Elsevier B.V. All rights reserved.

Eosinophils in Autoimmune Diseases

PubMed Central

Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

2017-01-01

Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

Bullous dermatosis associated with vancomycin extravasation.

PubMed

Bohm, Nicole M; Wong, Jeffrey G

2012-02-01

Cutaneous side effects related to vancomycin therapy have been reported including histamine-related reactions, linear IgA bullous dermatosis, Stevens-Johnson syndrome, maculopapular rash and drug rash with eosinophilia and systemic symptoms. In all instances, these reports were due to the systemic administration of vancomycin and subsequent immunological reactions to the medication. Drug extravasation into soft tissues can result in a variety of clinical outcomes usually related to physiochemical properties of the drug extravasated and its diluents or pharmacologic effects on the vasculature and tissue. The authors report a patient who experienced vancomycin extravasation that resulted in a localized bullous eruption resembling linear IgA bullous dermatosis, a phenomenon not previously described in the literature.

Tinea atypica: report of nine cases.

PubMed

Zisova, Liliya Georgieva; Dobrev, Hristo Petrov; Tchernev, Georgi; Semkova, Kristina; Aliman, Anastasia Atanasova; Chorleva, Kristina Ivanova; Chapanova, Antonina Teneva; Vutova, Nina Ivanova; Wollina, Uwe

2013-12-01

Fungal infections of the skin are a common condition, usually easy to diagnose and treat. When the infection is clinically mimicking another cutaneous disorder or when the clinical presentation is modified by the use of inappropriate treatment, it is referred to as tinea atypica or tinea incognito.We report a series of nine cases of patients with tinea atypica, imitating and diagnosed initially as different skin diseases. Two patients were defined as pyoderma in the facial and pubic regions (caused respectively by Trichophyton mentagrophytes var. mentagrophytes and Microsporum canis) and one as herpes zoster ophthalmicus (caused by Trichophyton rubrum). Six additional patients were initially misdiagnosed: (1) Plaque-like formation of the skin misdiagnosed as an impetiginized eczema (with isolated agent Trichophyton verrucosum). (2) A rare form of skin infection of the hand caused by T. rubrum, imitating clinically cutaneous infection with tuberculum mulgentium. (3) Rosacea-like dermatitis with an isolated agent Fusarium. (4) A patient with the typical clinical symptoms of seborrheic dermatitis of the face (and with isolated T. rubrum as a causative agent). (5) Another patient presented with a widespread folliculitis by Trichophyton mentagrophytes. (6) In a patient with bullous pemphigoid and immunosuppression pemphigoid-like eruptions were caused by Malassezia pachydermatis and T. rubrum. The diagnosis in the presented cases was based on direct microscopic examination with KOH and a culture on Sabouraud agar.After the diagnosis of tinea, treatment with topical and systemic antifungal agents was administrated, followed by complete clinical remissions in all cases.The clinical manifestations of tinea atypica can mimic a large number of other dermatoses, which often leads to misdiagnosing, and as a consequence--to serious difficulties in the management of clinical symptoms and in offering appropriate therapy.

A randomised controlled trial to compare the safety, effectiveness and cost-effectiveness of doxycycline (200 mg/day) with that of oral prednisolone (0.5 mg/kg/day) for initial treatment of bullous pemphigoid: the Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) trial.

PubMed

Chalmers, Joanne R; Wojnarowska, Fenella; Kirtschig, Gudula; Mason, James; Childs, Margaret; Whitham, Diane; Harman, Karen; Chapman, Anna; Walton, Shernaz; Schmidt, Enno; Godec, Thomas R; Nunn, Andrew J; Williams, Hywel C

2017-03-01

Bullous pemphigoid (BP) is an autoimmune blistering skin disorder with increased morbidity and mortality in the elderly. To evaluate the effectiveness, safety and cost-effectiveness of a strategy of initiating BP treatment with oral doxycycline or oral prednisolone. We hypothesised that starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral prednisolone. Pragmatic multicentre two-armed parallel-group randomised controlled trial with an economic evaluation. A total of 54 dermatology secondary care centres in the UK and seven in Germany. Adults with BP [three or more blisters at two sites and positive direct and/or indirect immunofluorescence (immunoglobulin G and/or complement component 3 immunofluorescence at the dermal-epidermal junction)] and able to give informed consent. Participants were allocated using online randomisation to initial doxycycline treatment (200 mg/day) or prednisolone (0.5 mg/kg/day). Up to 30 g/week of potent topical corticosteroids was permitted for weeks 1-3. After 6 weeks, clinicians could switch treatments or alter the prednisolone dose as per normal practice. Primary outcomes: (1) the proportion of participants with three or fewer blisters at 6 weeks (investigator blinded) and (2) the proportion with severe, life-threatening and fatal treatment-related events at 52 weeks. A regression model was used in the analysis adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Secondary outcomes included the effectiveness of blister control after 6 weeks, relapses, related adverse events and quality of life. The economic evaluation involved bivariate regression of costs and quality-adjusted life-years (QALYs) from a NHS perspective. In total, 132 patients were randomised to doxycycline and 121 to prednisolone. The mean patient age was 77.7 years and baseline severity was as follows: mild 31.6% (three to nine blisters), moderate 39.1% (10-30 blisters) and severe 29.3% (> 30 blisters). For those starting on doxycycline, 83 out of 112 (74.1%) had three or fewer blisters at 6 weeks, whereas for those starting on prednisolone 92 out of 101 (91.1%) had three or fewer blisters at 6 weeks, an adjusted difference of 18.6% in favour of prednisolone [90% confidence interval (CI) 11.1% to 26.1%], using a modified intention-to-treat (mITT) analysis. Per-protocol analysis showed similar results: 74.4% compared with 92.3%, an adjusted difference of 18.7% (90% CI 9.8% to 27.6%). The rate of related severe, life-threatening and fatal events at 52 weeks was 18.2% for those started on doxycycline and 36.6% for those started on prednisolone (mITT analysis), an adjusted difference of 19.0% (95% CI 7.9% to 30.1%; p  = 0.001) in favour of doxycycline. Secondary outcomes showed consistent findings. There was no significant difference in costs or QALYs per patient at 1 year between doxycycline-initiated therapy and prednisolone-initiated therapy (incremental cost of doxycycline-initiated therapy £959, 95% CI -£24 to £1941; incremental QALYs of doxycycline-initiated therapy -0.024, 95% CI -0.088 to 0.041). Using a willingness-to-pay criterion of < £20,000 per QALY gained, the net monetary benefit associated with doxycycline-initiated therapy was negative but imprecise (-£1432, 95% CI -£3094 to £230). A strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and considerably safer in the long term. The limitations of the trial were the wide non-inferiority margin, the moderate dropout rate and that serious adverse event collection was unblinded. Future work might include inducing remission with topical or oral corticosteroids and then randomising to doxycycline or prednisolone for maintenance. Current Controlled Trials ISRCTN13704604. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 10. See the NIHR Journals Library website for further project information.

Comparison of cost of immune globulin intravenous therapy to conventional immunosuppressive therapy in treating patients with autoimmune mucocutaneous blistering diseases.

PubMed

Daoud, Yassine J; Amin, Ketan G

2006-04-01

Autoimmune mucocutaneous blistering diseases (AMBD) are a group of potentially fatal diseases that affect the skin and mucous membranes. AMBD have different target antigens as well as variable clinical presentation, course, and prognosis. The mainstay of conventional immunosuppressive therapy (CIST) for AMBD is long-term high-dose systemic corticosteroids and immunosuppressive agents. Such therapy has proven effective in many patients; however, in some patients, the disease continues to progress with significant sequelae such as blindness, loss of voice, anal, and vaginal stenosis which causes poor quality of life. Furthermore, the CIST may have some serious side effects including opportunistic infections which may cause death. Immune globulin intravenous (IGIV) therapy has been reportedly used in the management of patients with AMBD refractory to CIST. IGIV has shown to be more clinically beneficial than CIST by bringing about long-term clinical remission and less recurrence. The high cost of the IGIV is of concern to patients, physicians, and insurance companies. In this report, we compare the cost of IGIV to that of CIST in treating a cohort of 15 mucous membrane pemphigoid (MMP), 10 ocular cicatricial pemphigoid (OCP), 15 bullous pemphigoid (BP), and 32 pemphigus vulgaris (PV) patients. In each cohort of patients, CIST had significant side effects, many of which were hazardous and required prolonged and frequent hospitalizations. Some of these side effects were severe enough to require discontinuation of the treatment. We consider the total cost of CIST to be the actual cost of the drug, plus the cost of management of the side effects produced by CIST. In the same patient cohort, no significant side effects to IGIV were observed. None of the IGIV treated patients required physician visits, laboratory tests, or hospitalizations specifically related to IGIV therapy. Hence, the total cost of the IGIV therapy is the actual cost of the IGIV only. The mean total cost of treatment of IGIV therapy is statistically significantly less than that of CIST during the entire course of the disease and on an annual basis. In conclusion, IGIV therapy is a safe, clinically beneficial, and a cost effective alternative treatment in patients with AMBD, non-responsive to CIST.

Beyond Psoriasis: Novel Uses for Biologic Response Modifiers in Pediatric Dermatology.

PubMed

Bellodi-Schmidt, Fernanda; Shah, Kara N

2016-01-01

Dermatologists have witnessed the increasing availability of novel biologic response modifiers for the treatment of inflammatory and autoimmune diseases in recent years. The most common dermatologic indication for the use of biologic response modifiers in adults is psoriasis, but the U.S. Food and Drug Administration has not approved any of these agents for use in any dermatologic disease in children with the exception of omalizumab, and as such, use in this population is considered off-label. In this review, we focus on the use of these agents in children to treat inflammatory skin diseases other than psoriasis, including atopic dermatitis, hidradenitis suppurativa, pemphigus vulgaris, bullous pemphigoid, and toxic epidermal necrolysis, with an emphasis on the use of etanercept, infliximab, rituximab, omalizumab, and ustekinumab. By highlighting novel uses of these agents, particularly for the treatment of dermatologic conditions for which optimal therapies are yet to be established, we hope to raise awareness of the potential use of this class of medications to treat inflammatory skin diseases in children. © 2015 Wiley Periodicals, Inc.

Serum lipocalin-2 levels are increased in patients with psoriasis.

PubMed

Kamata, M; Tada, Y; Tatsuta, A; Kawashima, T; Shibata, S; Mitsui, H; Asano, Y; Sugaya, M; Kadono, T; Kanda, N; Watanabe, S; Sato, S

2012-04-01

The protein lipocalin (LCN)-2 is known to be related to insulin resistance, obesity and atherosclerotic diseases. Psoriasis is an inflammatory skin disease related to metabolic syndrome. The aim of this study was to examine the relationship between serum LCN2 levels and indicators for metabolic syndrome and inflammatory cytokine levels in patients with psoriasis. Serum LCN2 levels were measured in patients with psoriasis, atopic dermatitis (AD) or bullous pemphigoid (BP), and compared with those of healthy controls. Serum LCN2 levels were also compared with several indicators for metabolic syndrome, and with serum levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α, two markers of inflammation. Serum LCN2 levels in patients with psoriasis were significantly higher than those of healthy controls, but there was no significant correlation between serum LCN2 and body mass index. Serum LCN2 levels also correlated with serum IL-6 and TNF-α levels in patients with psoriasis. Serum LCN2 levels are a general indicator for increased inflammation in the patients with psoriasis. © The Author(s). CED © 2012 British Association of Dermatologists.

Bullous phytophotodermatitis associated with high natural concentrations of furanocoumarins in limes.

PubMed

Wagner, Annette M; Wu, Jashin J; Hansen, Ronald C; Nigg, Herbert N; Beiere, Ross C

2002-03-01

Phytophotodermatitis is a phototoxic reaction, occurring in skin exposed to sunlight after contact with plants containing furanocoumarins. Typical reactions are mild, showing erythema with post-inflammatory hyperpigmentation. A 6-year-old boy presented with marked, symmetric, painful erythema and edema of both hands that rapidly developed into dramatic bullae covering the entire dorsum of the hands. The history revealed that the hands had been bathed in lime juice for a prolonged period in the preparation of limeade. This report documents an unusual bullous presentation of phytophotodermatitis resulting from contact with furanocoumarins in local limes. This study was conducted to identify and measure the inciting substances from the rind and pulp of the limes. Psoralen, xanthotoxin, bergapten, and isopimpinellin content were measured by gas chromatography and high-pressure liquid chromatography The rind contained 6- to 182-fold concentrations of all furanocoumarins measured when compared with pulp. Bergapten was the most abundant substance in the rind. Hydration of the skin during the preparation of limeade combined with increased levels of bergapten in local limes to produce a dramatic bullous reaction. We encourage clinicians to consider the possibility of phytophotodermatitis in severe bullous skin reactions. Copyright 2002, Elsevier Science (USA). All rights reserved.

Hemorrhagic Bullous Angina: A Case Report and Review of the Literature

PubMed Central

Rodrigues, Sara; Albrechete, Marielle; Monsanto, Rafael; Chagury, Azis; Lorenzetti, Fabio

2016-01-01

Hemorrhagic bullous angina (HBA) is described as the sudden onset of one or more bullous lesions in the oral cavity, not attributable to other vesiculobullous diseases, blood dyscrasias, or autoimmune and vascular diseases. These lesions occur almost exclusively in the oral cavity, particularly in the soft palate, and do not affect the masticatory mucosa. Here we present the case of a 57-year-old male who had a spontaneously ruptured hemorrhagic bulging in his soft palate diagnosed as HBA, along with discussion of the literature. In conclusion, HBA is a rare, benign, oral disease with low complication rates. Diagnosis is essentially clinical, and treatment consists of local hygiene and prevention of oral trauma. PMID:29392033

Hemorrhagic Bullous Angina: A Case Report and Review of the Literature.

PubMed

Rodrigues, Sara; Albrechete, Marielle; Monsanto, Rafael; Chagury, Azis; Lorenzetti, Fabio

2016-09-01

Hemorrhagic bullous angina (HBA) is described as the sudden onset of one or more bullous lesions in the oral cavity, not attributable to other vesiculobullous diseases, blood dyscrasias, or autoimmune and vascular diseases. These lesions occur almost exclusively in the oral cavity, particularly in the soft palate, and do not affect the masticatory mucosa. Here we present the case of a 57-year-old male who had a spontaneously ruptured hemorrhagic bulging in his soft palate diagnosed as HBA, along with discussion of the literature. In conclusion, HBA is a rare, benign, oral disease with low complication rates. Diagnosis is essentially clinical, and treatment consists of local hygiene and prevention of oral trauma.

[Dermatologic toxicities of immune checkpoint inhibitors].

PubMed

Sibaud, V; Boulinguez, S; Pagès, C; Riffaud, L; Lamant, L; Chira, C; Boyrie, S; Vigarios, E; Tournier, E; Meyer, N

2018-05-01

The development of immune checkpoint inhibitors (monoclonal antibodies targeting PD-1/PD-L1 or CTLA-4) represents a significant advance in the treatment of multiple cancers. Given their particular mechanism of action, which involves triggering CD4+/CD8+ T-cell activation and proliferation, they are associated with a specific safety profile. Their adverse events are primarily immune-related, and can affect practically all organs. In this context, dermatological toxicity is the most common, though it mostly remains mild to moderate and does not require discontinuation of treatment. More than a third of patients are faced with cutaneous adverse events, usually in the form of a maculopapular rash, pruritus or vitiligo (only in patients treated for melanoma). Much more specific dermatologic disorders, however, may occur such as lichenoid reactions, induced psoriasis, sarcoidosis, auto-immune diseases (bullous pemphigoid, dermatomyositis, alopecia areata), acne-like rash, xerostomia, etc. Rigorous dermatological evaluation is thus mandatory in the case of atypical, persistent/recurrent or severe lesions. In this article, we review the incidence and spectrum of dermatologic adverse events reported with immune checkpoint inhibitors. Finally, a management algorithm is proposed. Copyright © 2018. Published by Elsevier Masson SAS.

Microtubule-Actin Crosslinking Factor 1 and Plakins as Therapeutic Drug Targets.

PubMed

Quick, Quincy A

2018-01-26

Plakins are a family of seven cytoskeletal cross-linker proteins (microtubule-actin crosslinking factor 1 (MACF), bullous pemphigoid antigen (BPAG1) desmoplakin, envoplakin, periplakin, plectin, epiplakin) that network the three major filaments that comprise the cytoskeleton. Plakins have been found to be involved in disorders and diseases of the skin, heart, nervous system, and cancer that are attributed to autoimmune responses and genetic alterations of these macromolecules. Despite their role and involvement across a spectrum of several diseases, there are no current drugs or pharmacological agents that specifically target the members of this protein family. On the contrary, microtubules have traditionally been targeted by microtubule inhibiting agents, used for the treatment of diseases such as cancer, in spite of the deleterious toxicities associated with their clinical utility. The Research Collaboratory for Structural Bioinformatics (RCSB) was used here to identify therapeutic drugs targeting the plakin proteins, particularly the spectraplakins MACF1 and BPAG1, which contain microtubule-binding domains. RCSB analysis revealed that plakin proteins had 329 ligands, of which more than 50% were MACF1 and BPAG1 ligands and 10 were documented, clinically or experimentally, to have several therapeutic applications as anticancer, anti-inflammatory, and antibiotic agents.

A randomized, first-in-human, healthy volunteer trial of BIVV009, a humanized antibody for the specific inhibition of the classical complement pathway.

PubMed

Bartko, Johann; Schoergenhofer, Christian; Schwameis, Michael; Firbas, Christa; Beliveau, Martin; Chang, Colin; Marier, Jean-Francois; Nix, Darrell; Gilbert, James C; Panicker, Sandip; Jilma, Bernd

2018-05-08

Aberrant activation of the classical complement pathway is the common underlying pathophysiology of orphan diseases such as bullous pemphigoid, antibody-mediated rejection of organ transplants, cold agglutinin disease and warm autoimmune haemolytic anaemia. Therapeutic options for these complement-mediated disorders are limited and BIVV009, a humanized monoclonal antibody directed against complement factor C1s, may be potentially useful for inhibition of the classical complement pathway. A phase-1, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial of single and multiple doses of BIVV009 or placebo was conducted in 64 volunteers to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic profiles. Single and multiple infusions of BIVV009 were well tolerated without any safety concerns. BIVV009 exhibited a steep concentration-effect relationship with a Hill coefficient of 2.4, and an IC90 of 15.5 µg/mL. This study establishes the foundation for using BIVV009 as a highly selective inhibitor of the classical complement pathway in different diseases. This article is protected by copyright. All rights reserved. © 2018 American Society for Clinical Pharmacology and Therapeutics.

Churg-Strauss syndrome with coexistence of eosinophilic vasculitis, granulomatous phlebitis and granulomatous dermatitis in bullous pemphigoid-like blisters.

PubMed

Ishibashi, Masafumi; Kudo, Saori; Yamamoto, Kyoko; Shimai, Nobuko; Chen, Ko-Ron

2011-03-01

The main histopathological features in the cutaneous lesions of Churg-Strauss syndrome (CSS) are dermal leukocytoclastic vasculitis with a variable eosinophilic infiltrate and non-vasculitic tissue eosinophilia with granuloma formation. This wide histopathological spectrum may account for the various skin manifestations of CSS. However, the unique histopathological combination of dermal eosinophilic vasculitis and subcutaneous granulomatous phlebitis accompanied by bulla formation has not been previously described. We report an unusual CSS case showing dermal necrotizing eosinophilic vasculitis and granulomatous phlebitis in purpuric lesions coupled with subepidermal blistering. The blisters showed dermal granulomatous dermatitis and eosinophilia without evidence of vasculitis. Dermal necrotizing eosinophilic vasculitis was characterized by fibrinoid alteration of the vessel wall, a prominent perivascular eosinophilic infiltrate, a few infiltrating histiocytes along the affected vessel wall, and the absence of neutrophilic infiltration. The underlying subcutaneous granulomatous phlebitis was characterized by an angiocentric histiocytic infiltrate surrounded by marked eosinophilic infiltrate. Deposition of cytotoxic proteins and radicals derived from eosinophils in the vessel walls and papillary dermis followed by a secondary granulomatous response may account for the unique clinical and histopathological features in this case. Copyright © 2010 John Wiley & Sons A/S.

Microtubule-Actin Crosslinking Factor 1 and Plakins as Therapeutic Drug Targets

PubMed Central

Quick, Quincy A.

2018-01-01

Plakins are a family of seven cytoskeletal cross-linker proteins (microtubule-actin crosslinking factor 1 (MACF), bullous pemphigoid antigen (BPAG1) desmoplakin, envoplakin, periplakin, plectin, epiplakin) that network the three major filaments that comprise the cytoskeleton. Plakins have been found to be involved in disorders and diseases of the skin, heart, nervous system, and cancer that are attributed to autoimmune responses and genetic alterations of these macromolecules. Despite their role and involvement across a spectrum of several diseases, there are no current drugs or pharmacological agents that specifically target the members of this protein family. On the contrary, microtubules have traditionally been targeted by microtubule inhibiting agents, used for the treatment of diseases such as cancer, in spite of the deleterious toxicities associated with their clinical utility. The Research Collaboratory for Structural Bioinformatics (RCSB) was used here to identify therapeutic drugs targeting the plakin proteins, particularly the spectraplakins MACF1 and BPAG1, which contain microtubule-binding domains. RCSB analysis revealed that plakin proteins had 329 ligands, of which more than 50% were MACF1 and BPAG1 ligands and 10 were documented, clinically or experimentally, to have several therapeutic applications as anticancer, anti-inflammatory, and antibiotic agents. PMID:29373494

BP180 dysfunction triggers spontaneous skin inflammation in mice.

PubMed

Zhang, Yang; Hwang, Bin-Jin; Liu, Zhen; Li, Ning; Lough, Kendall; Williams, Scott E; Chen, Jinbo; Burette, Susan W; Diaz, Luis A; Su, Maureen A; Xiao, Shengxiang; Liu, Zhi

2018-06-04

BP180, also known as collagen XVII, is a hemidesmosomal component and plays a key role in maintaining skin dermal/epidermal adhesion. Dysfunction of BP180, either through genetic mutations in junctional epidermolysis bullosa (JEB) or autoantibody insult in bullous pemphigoid (BP), leads to subepidermal blistering accompanied by skin inflammation. However, whether BP180 is involved in skin inflammation remains unknown. To address this question, we generated a BP180-dysfunctional mouse strain and found that mice lacking functional BP180 (termed Δ NC16A ) developed spontaneous skin inflammatory disease, characterized by severe itch, defective skin barrier, infiltrating immune cells, elevated serum IgE levels, and increased expression of thymic stromal lymphopoietin (TSLP). Severe itch is independent of adaptive immunity and histamine, but dependent on increased expression of TSLP by keratinocytes. In addition, a high TSLP expression is detected in BP patients. Our data provide direct evidence showing that BP180 regulates skin inflammation independently of adaptive immunity, and BP180 dysfunction leads to a TSLP-mediated itch. The newly developed mouse strain could be a model for elucidation of disease mechanisms and development of novel therapeutic strategies for skin inflammation and BP180-related skin conditions.

Profibrotic Phenotype of Conjunctival Fibroblasts from Mucous Membrane Pemphigoid

PubMed Central

Saw, Valerie P.J.; Schmidt, Enno; Offiah, Ifeoma; Galatowicz, Grazyna; Zillikens, Detlef; Dart, John K.G.; Calder, Virginia L.; Daniels, Julie T.

2011-01-01

Ocular mucous membrane pemphigoid is an immunobullous disease in which excessive conjunctival fibrosis causes blindness, and the pathogenesis of scarring is incompletely understood. To establish whether profibrotic fibroblasts with an altered phenotype exist in ocular mucous membrane pemphigoid, we compared the functional characteristics of pemphigoid conjunctival fibroblasts to normal conjunctival fibroblasts with respect to cell division; migration; collagen contraction; matrix metalloproteinase, secretion of collagen and chemokines; and myofibroblast differentiation. We found that pemphigoid fibroblasts showed increased cell division (P = 0.01), increased migration in serum-free medium (72 ± 18 migrated cells versus 33 ± 11, P = 0.04), increased collagen contraction in the presence of 10 ng/ml tumor necrosis factor-α, increased collagen type I secretion (P = 0.03), increased secretion of matrix metalloproteinase-3 (P = 0.03), and increased secretion of eotaxin in response to interleukin-13 (P = 0.04). Differences between pemphigoid and normal conjunctival fibroblasts with respect to collagen contraction and MMP secretion in the presence of interleukin-13 were also observed. Together, these findings indicate that pemphigoid conjunctival fibroblasts have a profibrotic phenotype that is maintained in vitro. No differences between pemphigoid fibroblasts obtained from acutely inflamed versus clinically uninflamed conjunctiva were observed. Developing effective antifibrotic therapies will require understanding of the mechanisms that both induce and maintain the profibrotic phenotype. PMID:21224056

Polymicrobial and microsporidial keratitis in a patient using Boston scleral contact lens for Sjogren's syndrome and ocular cicatricial pemphigoid.

PubMed

Fernandes, Merle; Sharma, Savitri

2013-04-01

To report a rare case of microsporidial and polymicrobial keratitis in a patient with Sjogren's syndrome and ocular cicatricial pemphigoid. This is a descriptive case report. A 66-year-old lady diagnosed with Sjogren's syndrome (SS) and ocular cicatricial pemphigoid (OCP) presented to us with microbial keratitis after using a Boston sclera contact lens for a painful epithelial defect. After 9 days of medical treatment, she underwent therapeutic penetrating keratoplasty. 10% potassium hydroxide and calcofluor white wet mount revealed microsporidial spores. Gram positive cocci and Gram variable bacilli on Gram stain were identified as Staphylococcus epidermidis and Corynebacterium accolens in culture. Histopathological examination of the corneal tissue confirmed the presence of microsporidial spores. Microsporidal keratitis can occur in patients with severe ocular surface disease due to SS and OCP. Predisposing factors include dry eye, local and systemic immunosuppression and Boston scleral contact lens. Early surgical intervention may be needed to eradicate the infection. Copyright © 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Increased risk of pemphigoid following scabies: a population-based matched-cohort study.

PubMed

Chung, S-D; Lin, H-C; Wang, K-H

2014-05-01

No prior study has investigated the possibility that scabies patients may be at an increased risk for developing pemphigoid. To evaluate the risk of pemphigoid following scabies during a 3-year follow-up period using a Taiwanese population-based claims database and taking clinical and demographic characteristics into consideration. This investigation consisted of a study group of 6793 subjects with a diagnosis of scabies and 33 965 randomly selected subjects used as a comparison group. Each patient was tracked for 3 years following their index dates to identify those who received a subsequent diagnosis of pemphigoid. Stratified Cox proportional hazards regressions were used to compute the hazard ratio (HR) of pemphigoid during the 3-year follow-up period. Of the 40 758 subjects, 52 (0.13%) had received a diagnosis of pemphigoid during the 3-year follow-up period; 33 (0.49% of the study group) were from the study group and 19 (0.06% of the comparison group) were from the comparison group. Compared to subjects without scabies, the HR for pemphigoid for subjects with scabies was 5.93 within the 3-year follow-up period following the index date after adjusting for monthly income, hypertension, diabetes, obesity, psoriasis, stroke, dementia, Parkinson's disease, coronary heart disease, schizophrenia or bipolar disorder, and after censoring those that died during the follow-up period. This study detected an increased risk for pemphigoid among patients suffering from scabies. Physicians treating elderly patients with a history of scabies should be alert to the development of pemphigoid. © 2013 The Authors Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology.

Association of serious infections with pemphigus and pemphigoid: analysis of the Nationwide Inpatient Sample.

PubMed

Ren, Z; Narla, S; Hsu, D Y; Silverberg, J I

2018-03-25

Pemphigus and pemphigoid are blistering disorders associated with barrier disruption, immune dysregulation and use of immunosuppressing systemic therapy, all of which may predispose towards serious infections. To determine whether pemphigus and pemphigoid are associated with increased likelihood of serious infections and the impact of such infections on mortality and cost of care. We analysed data from the 2002 to 2012 Nationwide Inpatient Sample, including a representative 20% sample of all hospitalizations in the US (total n = 72 108 077 adults). Overall, 54.6% (95% CI: 53.6-55.6%) and 50.4% (49.0-51.8%) of inpatients with either pemphigoid or pemphigus had a diagnosis of serious infection, respectively, compared with 25.4% (25.2-25.6%) in those without either diagnosis. In multivariable logistic regression models controlling for gender, age, race/ethnicity and insurance status, pemphigoid or pemphigus was associated with 26 or 21 of 48 infections examined, respectively. In particular, both pemphigoid and pemphigus were associated with higher odds of infections of the skin, bones, respiratory, gastrointestinal, genitourinary and central nervous system, septicaemia and antibiotic-resistant infections. Pemphigus was also associated with aspergillus, pharyngitis and Pneumocystis Carinii pneumonia. Associations of any serious infection in both pemphigoid and pemphigus patients were older age, non-White race, lower median household income, government or no insurance, higher number of chronic conditions, and those with a diagnosis of Cushing's syndrome, diabetes, cancer or autoimmune disease. The diagnosis of any serious infection vs. no infection was associated with increased inpatient mortality and costs in both pemphigoid (mortality: 7.85% vs. 2.84%; cost: $16 115 vs. $10 653) and pemphigus (mortality: 6.78% vs. 1.88%; cost: $17 707 vs. $11 545) inpatients (P < 0.0001 for all). Adults with pemphigus or pemphigoid had increased cutaneous, respiratory, multi-organ and systemic infections, which were associated with considerable inpatient mortality and cost burden. Moreover, there were significant clinical and healthcare disparities with respect to infections in patients with pemphigus or pemphigoid. © 2018 European Academy of Dermatology and Venereology.

First identification of the herpes simplex virus by skin-dedicated ex vivo fluorescence confocal microscopy during herpetic skin infections.

PubMed

Cinotti, E; Perrot, J L; Labeille, B; Campolmi, N; Thuret, G; Naigeon, N; Bourlet, T; Pillet, S; Cambazard, F

2015-06-01

Skin-dedicated ex vivo fluorescence confocal microscopy (FCM) has so far been used to identify cutaneous tumours on freshly excised samples using acridine orange as fluorochrome. To use FCM for a new indication, namely, the identification of the herpes simplex virus (HSV) in skin lesions, using fluorescent antibodies. Six roof samples from skin vesicles suspicious for HSV lesions were incubated with anti-HSV-1 and anti-HSV-2 antibodies coupled with fluorescein isothiocyanate, and examined under skin-dedicated ex vivo FCM. The positive controls were swabs taken from the floor of each vesicle and observed under conventional direct fluorescence assay (DFA) and by viral cultures. Roof samples from three bullae of bullous pemphigoid were the negative controls. Using ex vivo FCM, the samples from the lesions clinically suspicious for HSV infection were seen to be fluorescent after incubation with anti-HSV-1, and were negative after incubation with anti-HSV-2 antibodies. Conventional DFA with an optical microscope and cultures confirmed the presence of HSV-1 infection. By using fluorescent antibodies to identify precise structures, ex vivo FCM can be used for indications other than tumour identification. More specifically, it can be an additional diagnostic tool for HSV infection. © 2014 British Association of Dermatologists.

Professional oral hygiene treatment and detailed oral hygiene instructions in patients affected by mucous membrane pemphigoid with specific gingival localization: a pilot study in 12 patients.

PubMed

Arduino, P G; Lopetuso, E; Carcieri, P; Giacometti, S; Carbone, M; Tanteri, C; Broccoletti, R

2012-05-01

The aim of this prospective case series was to assess the clinical efficiency of an oral hygiene protocol in patients affected by mucous membrane pemphigoid (MMP) with specific gingival localization, before starting any medical treatment. Patients received oral hygiene instruction followed by non-surgical periodontal therapy including oral hygiene instructions in a 3-week cohort study. Clinical outcome variables were recorded at baseline and 5 weeks after intervention and included, as periodontal parameters, full mouth plaque (FMPS) and bleeding (FMBS) scores and patient-related outcomes (visual analogue score of pain). A total of 12 patients were recruited. The mean age at presentation was 59.5 ± 14.52 years. Five weeks after finishing the oral hygiene and periodontal therapy protocol, a statistical significant reduction was observed for FMPS (P = 0.001), FMBS (P = 0.022) and reported pain (P = 0.0028). Professional oral hygiene procedures and non-surgical periodontal therapy are connected with improvement of gingival status and decrease in gingival-related pain, in female patients affected by MMP with specific gingival localization. © 2011 John Wiley & Sons A/S.

A Clinicopathological Study of Pemphigus in Eastern India with Special Reference to Direct Immunofluorescence

PubMed Central

Chowdhury, Joyeeta; Datta, Pijush Kanti; Chowdhury, Satyendra Nath; Das, Nilay Kanti

2016-01-01

Background: Pemphigus is a group of chronic autoimmune vesico-bullous disorders in which the epidermis and the basement membrane zone are the focus of attack resulting in cutaneous and mucosal blister formation. Direct immunofluorescence (DIF) test is a very sensitive test for the diagnosis Aim: To study the clinico histopathological patterns of pemphigus in eastern India. The study also aims to correlate DIF with clinical and histologic findings as well as severity of skin involvement [scoring systems]. Materials and Methods: Total 41 patients were studied over a period of 1 year in the Post-graduate centre of Dermatology in Eastern India. DIF, histopathology and clinical data were correlated. Results: In our study Pemphigus vulgaris (PV) was the predominant type with 32 cases followed by 8 cases of pemphigus foliaceus (PF) and a single case of IgA pemphigus. Mean age at presentation was late middle age. Majority of the patients, 26 (63.41%) initially had cutaneous involvement followed by mucosal involvement. In this study group 36 (87.80%) patients showed acantholytic cells on histopathological examination. Most patients of PV showed suprabasal blister 20 (62.50%) followed by intraspinous 5 (15.62%) and subcorneal 5 (15.62%) blister. In majority 28 (87.50%) of the PV patients IgG and C3 antibodies were deposited throughout the epidermis. The strength of antibody positivity was strong in most of the patients (71.87%). In cases of PF mostly IgG 6 (75%) antibodies were deposited in the upper epidermis. DIF intensity had poor correlation with disease activity/severity except in PF. Conclusion: Almost 85.36% cases of pemphigus were diagnosed clinicopathologically. But 6 cases couldn’t be diagnosed accurately on clinicopathological basis and in them DIF was confirmatory. Two cases of pure mucosal PV and 1 case of IgA pemphigus was confirmed by DIF. Two cases of bullous pemphigoid clinico-histologically mimicking PV were also excluded by DIF. So it appears from our study that DIF is confirmatory for diagnosis of pemphigus in all cases. PMID:27293249

[A severe epicutaneous test reaction to the bufexamac in a hemorrhoidal therapeutic preparation].

PubMed

Bauer, A; Greif, C; Gebhardt, M; Elsner, P

1999-10-08

A 49-year-old woman presented with acute perianal vesicular/bullous contact dermatitis. Other areas were over the trunk, face, neck and wrists. She reported occasional application of an ointment (Mastu S) to treat her hemorrhoids. Patch tests (basic series, anal block, own ointment, local anesthetic, cosmetics) provoked strong vesicular and bullous reactions of persisting crescendo type, spreading far beyond the site of application, to Bufexamac, to a derivative of hydroxxamine acid, and to local applied ointment with mild or moderate antiinflammatory action. A week after the patch tests there was a flare-up of the previous foci of dermatitis. These reactions subsided two days later after intravenous injection of prednisolone. The skin lesions healed after rapid reduction of the systemic treatment and local application of corticosteroids, bathing with tanning substances and basic preparations. While Bufexamac is not absorbed when applied rectally, perianal contamination may not be avoidable on intra-anal application and can produce sensitization.

Methimazole-induced bullous systemic lupus erythematosus: a case report.

PubMed

Seo, Ji-Yeon; Byun, Hee-Jin; Cho, Kwang-Hyun; Lee, Eun Bong

2012-07-01

Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.

Pemphigus

MedlinePlus

... risk for pemphigus. Pemphigoid is also an autoimmune skin disease. It leads to deep blisters that do not break easily. Pemphigoid is most common in older adults and may be fatal for older, sick patients. ...

Cloning and characterization of mouse ACF7, a novel member of the dystonin subfamily of actin binding proteins.

PubMed

Bernier, G; Mathieu, M; De Repentigny, Y; Vidal, S M; Kothary, R

1996-11-15

We have recently cloned the gene responsible for the mouse neurological disorder dystonia musculorum. The predicted product of this gene, dystonin (Dst), is a neural isoform of bullous pemphigoid antigen 1 (Bpag1) with an N-terminal actin binding domain. Here we report on the cloning and characterization of mouse ACF7. Sequence analysis revealed extended homology of mACF7 with both the actin binding domain (ABD) and the Bpag1 portions of dystonin. Moreover, mACF7 and Dst display similar isoform diversity and encode similar sized transcripts in the nervous system. Phylogenetic analysis of mACF7 and dystonin ABD sequences suggests a recent evolutionary origin and that these proteins form a separate novel subfamily within the beta-spectrin superfamily of actin binding proteins. Given the implication of several actin binding proteins in genetic disorders, it is important to know the pattern of mACF7 expression. mACF7 transcripts are detected principally in lung, brain, spinal cord, skeletal and cardiac muscle, and skin. Intriguingly, mACF7 expression in lung is strongly induced just before birth and is restricted to type II alveolar cells. To determine whether spontaneous mutants that may be defective in mACF7 exist, we have mapped the mACF7 gene to mouse chromosome 4.

Epidemiological, clinical and allergological observations on pompholyx.

PubMed

Lodi, A; Betti, R; Chiarelli, G; Urbani, C E; Crosti, C

1992-01-01

We have studied a group of 104 patients with pompholyx, to investigate the relationship between allergological factors and its etiopathogenesis. The following examinations were performed: blood sampling (routine tests and IgE levels), allergological tests (patch, prick, intradermal, and oral provovation tests with nickel sulphate), skin biopsy to exclude pemphigus vulgaris or bullous pemphigoid. An accurate history of familial and personal allergic diathesis was enquired for and various possible aggravating factors (season, microclimate, perspiration and emotional stress) were considered. The results were age and sex-matched with a healthy control group (208 subjects). We found familial and personal atopic diathesis in 50% of patients versus 11.5% of controls (p less than 0.001); 39 patients (37.49%) also had high levels of IgE. Nickel sulphate was the allergen with the highest positivity on patch testing: 20.19% versus 6.25% of the control group (p less than 0.001). The % of patients allergic to nickel reached 26%, including those (6 patients) reacting to the oral provocation test. Season (43 patients) and hyperhidrosis (38) were the aggravating factors most commonly claimed. We detected no correlation between age, sex, grading of pompholyx and the allergological parameters investigated. Though several different allergological findings have previously been reported in dyshidrosis, their role in its pathogenesis has not yet been fully explained. We think that different haptens or antigens can produce the same clinical and histological picture of pompholyx in predisposed subjects.

Defenders and Challengers of Endothelial Barrier Function

PubMed Central

Rahimi, Nader

2017-01-01

Regulated vascular permeability is an essential feature of normal physiology and its dysfunction is associated with major human diseases ranging from cancer to inflammation and ischemic heart diseases. Integrity of endothelial cells also play a prominent role in the outcome of surgical procedures and organ transplant. Endothelial barrier function and integrity are regulated by a plethora of highly specialized transmembrane receptors, including claudin family proteins, occludin, junctional adhesion molecules (JAMs), vascular endothelial (VE)-cadherin, and the newly identified immunoglobulin (Ig) and proline-rich receptor-1 (IGPR-1) through various distinct mechanisms and signaling. On the other hand, vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor, VEGF receptor-2, play a central role in the destabilization of endothelial barrier function. While claudins and occludin regulate cell–cell junction via recruitment of zonula occludens (ZO), cadherins via catenin proteins, and JAMs via ZO and afadin, IGPR-1 recruits bullous pemphigoid antigen 1 [also called dystonin (DST) and SH3 protein interacting with Nck90/WISH (SH3 protein interacting with Nck)]. Endothelial barrier function is moderated by the function of transmembrane receptors and signaling events that act to defend or destabilize it. Here, I highlight recent advances that have provided new insights into endothelial barrier function and mechanisms involved. Further investigation of these mechanisms could lead to the discovery of novel therapeutic targets for human diseases associated with endothelial dysfunction. PMID:29326721

Complement System in Dermatological Diseases – Fire Under the Skin

PubMed Central

Panelius, Jaana; Meri, Seppo

2015-01-01

The complement system plays a key role in several dermatological diseases. Overactivation, deficiency, or abnormality of the control proteins are often related to a skin disease. Autoimmune mechanisms with autoantibodies and a cytotoxic effect of the complement membrane attack complex on epidermal or vascular cells can cause direct tissue damage and inflammation, e.g., in systemic lupus erythematosus (SLE), phospholipid antibody syndrome, and bullous skin diseases like pemphigoid. By evading complement attack, some microbes like Borrelia spirochetes and staphylococci can persist in the skin and cause prolonged symptoms. In this review, we present the most important skin diseases connected to abnormalities in the function of the complement system. Drugs having an effect on the complement system are also briefly described. On one hand, drugs with free hydroxyl on amino groups (e.g., hydralazine, procainamide) could interact with C4A, C4B, or C3 and cause an SLE-like disease. On the other hand, progress in studies on complement has led to novel anti-complement drugs (recombinant C1-inhibitor and anti-C5 antibody, eculizumab) that could alleviate symptoms in diseases associated with excessive complement activation. The main theme of the manuscript is to show how relevant the complement system is as an immune effector system in contributing to tissue injury and inflammation in a broad range of skin disorders. PMID:25688346

A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70

PubMed Central

Chan, Alice Y.; Punwani, Divya; Kadlecek, Theresa A.; Cowan, Morton J.; Olson, Jean L.; Mathes, Erin F.; Sunderam, Uma; Man Fu, Shu; Srinivasan, Rajgopal; Kuriyan, John; Brenner, Steven E.; Weiss, Arthur

2016-01-01

A brother and sister developed a previously undescribed constellation of autoimmune manifestations within their first year of life, with uncontrollable bullous pemphigoid, colitis, and proteinuria. The boy had hemophilia due to a factor VIII autoantibody and nephrotic syndrome. Both children required allogeneic hematopoietic cell transplantation (HCT), which resolved their autoimmunity. The early onset, severity, and distinctive findings suggested a single gene disorder underlying the phenotype. Whole-exome sequencing performed on five family members revealed the affected siblings to be compound heterozygous for two unique missense mutations in the 70-kD T cell receptor ζ-chain associated protein (ZAP-70). Healthy relatives were heterozygous mutation carriers. Although pre-HCT patient T cells were not available, mutation effects were determined using transfected cell lines and peripheral blood from carriers and controls. Mutation R192W in the C-SH2 domain exhibited reduced binding to phosphorylated ζ-chain, whereas mutation R360P in the N lobe of the catalytic domain disrupted an autoinhibitory mechanism, producing a weakly hyperactive ZAP-70 protein. Although human ZAP-70 deficiency can have dysregulated T cells, and autoreactive mouse thymocytes with weak Zap-70 signaling can escape tolerance, our patients’ combination of hypomorphic and activating mutations suggested a new disease mechanism and produced previously undescribed human ZAP-70–associated autoimmune disease. PMID:26783323

Accidental bullous phototoxic reactions to bergamot aromatherapy oil.

PubMed

Kaddu, S; Kerl, H; Wolf, P

2001-09-01

Oil of bergamot is an extract from the rind of bergamot orange (Citrus aurantium ssp bergamia) that has a pleasant, refreshing scent; until a few years ago it had been widely used as an ingredient in cosmetics but was restricted or banned in most countries because of certain adverse effects. More recently, oil of bergamot preparations have been gaining renewed popularity in aromatherapy. Oil of bergamot possesses photosensitive and melanogenic properties because of the presence of furocoumarins, primarily bergapten (5-methoxypsoralen [5-MOP]). However, 5-MOP is also potentially phototoxic and photomutagenic. Despite its increasing application, there are only a few recent reports of phototoxic reactions to bergamot aromatherapy oil. We describe two patients with localized and disseminated bullous phototoxic skin reactions developing within 48 to 72 hours after exposure to bergamot aromatherapy oil and subsequent ultraviolet exposure. One patient (case 2) had no history of direct contact with aromatherapy oil but developed bullous skin lesions after exposure to aerosolized (evaporated) aromatherapy oil in a sauna and subsequent UVA radiation in a tanning salon. This report highlights the potential health hazard related to the increasing use of psoralen-containing aromatherapy oils.

Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors.

PubMed

Strauss, Julius; Heery, Christopher R; Schlom, Jeffrey; Madan, Ravi A; Cao, Liang; Kang, Zhigang; Lamping, Elizabeth; Marté, Jennifer L; Donahue, Renee N; Grenga, Italia; Cordes, Lisa; Christensen, Olaf; Mahnke, Lisa; Helwig, Christoph; Gulley, James L

2018-03-15

Purpose: M7824 (MSB0011359C) is an innovative first-in-class bifunctional fusion protein composed of a mAb against programmed death ligand 1 (PD-L1) fused to a TGFβ "trap." Experimental Design: In the 3+3 dose-escalation component of this phase I study (NCT02517398), eligible patients with advanced solid tumors received M7824 at 1, 3, 10, or 20 mg/kg once every 2 weeks until confirmed progression, unacceptable toxicity, or trial withdrawal; in addition, a cohort received an initial 0.3 mg/kg dose to evaluate pharmacokinetics/pharmacodynamics, followed by 10 mg/kg dosing. The primary objective is to determine the safety and maximum tolerated dose (MTD); secondary objectives include pharmacokinetics, immunogenicity, and best overall response. Results: Nineteen heavily pretreated patients with ECOG 0-1 have received M7824. Grade ≥3 treatment-related adverse events occurred in four patients (skin infection secondary to localized bullous pemphigoid, asymptomatic lipase increase, colitis with associated anemia, and gastroparesis with hypokalemia). The MTD was not reached. M7824 saturated peripheral PD-L1 and sequestered any released plasma TGFβ1, -β2, and -β3 throughout the dosing period at >1 mg/kg. There were signs of efficacy across all dose levels, including one ongoing confirmed complete response (cervical cancer), two durable confirmed partial responses (PR; pancreatic cancer; anal cancer), one near-PR (cervical cancer), and two cases of prolonged stable disease in patients with growing disease at study entry (pancreatic cancer; carcinoid). Conclusions: M7824 has a manageable safety profile in patients with heavily pretreated advanced solid tumors. Early signs of efficacy are encouraging, and multiple expansion cohorts are ongoing in a range of tumors. Clin Cancer Res; 24(6); 1287-95. ©2018 AACR . ©2018 American Association for Cancer Research.

Linear IgA bullous dermatosis in a neonate.

PubMed

Hruza, L L; Mallory, S B; Fitzgibbons, J; Mallory, G B

1993-06-01

A newborn black boy had two facial blisters at birth that progressed to bullous lesions over the trunk, genitals, extremities, and oral and tracheal mucosa. A biopsy specimen demonstrated a subepidermal bulla with mixed eosinophilic and neutrophilic, inflammatory infiltrate. Direct immunofluorescence showed linear IgA, IgG, and C3 depositions along the basement membrane zone, consistent with a diagnosis of childhood linear IgA bullous dermatosis (chronic bullous dermatosis of childhood). The skin disease was controlled with combined prednisone and dapsone. This is the youngest reported patient with the disease. Linear IgA bullous dermatosis should be considered in the differential diagnosis of blistering diseases of the newborn, and immunofluorescence should be performed on a skin biopsy specimen.

A 12-year retrospective review of bullous systemic lupus erythematosus in cutaneous and systemic lupus erythematosus patients.

PubMed

Chanprapaph, K; Sawatwarakul, S; Vachiramon, V

2017-10-01

Objective The aim of this study was to investigate the clinical features, laboratory findings, systemic manifestations, treatment and outcome of patients with bullous systemic lupus erythematosus in a tertiary care center in Thailand. Methods We performed a retrospective review from 2002 to 2014 of all patients who fulfilled the diagnostic criteria for bullous systemic lupus erythematosus to evaluate for the clinical characteristics, extracutaneous involvement, histopathologic features, immunofluorescence pattern, serological abnormalities, internal organ involvement, treatments and outcome. Results Among 5149 patients with cutaneous lupus erythematosus and/or systemic lupus erythematosus, 15 developed vesiculobullous lesions. Ten patients had validation of the diagnosis of bullous systemic lupus erythematosus, accounting for 0.19%. Bullous systemic lupus erythematosus occurred after the diagnosis of systemic lupus erythematosus in six patients with a median onset of 2.5 months (0-89). Four out of 10 patients developed bullous systemic lupus erythematosus simultaneously with systemic lupus erythematosus. Hematologic abnormalities and renal involvement were found in 100% and 90%, respectively. Polyarthritis (40%) and serositis (40%) were less frequently seen. Systemic corticosteroids, immunosuppressants, antimalarials and dapsone offered resolution of cutaneous lesions. Conclusion Bullous systemic lupus erythematosus is an uncommon presentation of systemic lupus erythematosus. Blistering can occur following or simultaneously with established systemic lupus erythematosus. We propose that clinicians should carefully search for systemic involvement, especially hematologic and renal impairment, in patients presenting with bullous systemic lupus erythematosus.

Immunoglobulin E-Mediated Autoimmunity

PubMed Central

Maurer, Marcus; Altrichter, Sabine; Schmetzer, Oliver; Scheffel, Jörg; Church, Martin K.; Metz, Martin

2018-01-01

The study of autoimmunity mediated by immunoglobulin E (IgE) autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP), and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them. PMID:29686678

Transgenic expression of neuronal dystonin isoform 2 partially rescues the disease phenotype of the dystonia musculorum mouse model of hereditary sensory autonomic neuropathy VI

PubMed Central

Ferrier, Andrew; Sato, Tadasu; De Repentigny, Yves; Gibeault, Sabrina; Bhanot, Kunal; O'Meara, Ryan W.; Lynch-Godrei, Anisha; Kornfeld, Samantha F.; Young, Kevin G.; Kothary, Rashmi

2014-01-01

A newly identified lethal form of hereditary sensory and autonomic neuropathy (HSAN), designated HSAN-VI, is caused by a homozygous mutation in the bullous pemphigoid antigen 1 (BPAG1)/dystonin gene (DST). The HSAN-VI mutation impacts all major neuronal BPAG1/dystonin protein isoforms: dystonin-a1, -a2 and -a3. Homozygous mutations in the murine Dst gene cause a severe sensory neuropathy termed dystonia musculorum (dt). Phenotypically, dt mice are similar to HSAN-VI patients, manifesting progressive limb contractures, dystonia, dysautonomia and early postnatal death. To obtain a better molecular understanding of disease pathogenesis in HSAN-VI patients and the dt disorder, we generated transgenic mice expressing a myc-tagged dystonin-a2 protein under the regulation of the neuronal prion protein promoter on the dtTg4/Tg4 background, which is devoid of endogenous dystonin-a1 and -a2, but does express dystonin-a3. Restoring dystonin-a2 expression in the nervous system, particularly within sensory neurons, prevented the disorganization of organelle membranes and microtubule networks, attenuated the degeneration of sensory neuron subtypes and ameliorated the phenotype and increased life span in these mice. Despite these improvements, complete rescue was not observed likely because of inadequate expression of the transgene. Taken together, this study provides needed insight into the molecular basis of the dt disorder and other peripheral neuropathies including HSAN-VI. PMID:24381311

Statins: novel additions to the dermatologic arsenal?

PubMed

Namazi, M R

2004-06-01

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), atorvastatin, cerivastatin, fluvastatin, pravastatin, lovastatin and simvastatin, reduce atherogenesis and cardiovascular morbidity. Besides, there is growing evidence that statins have immunomodulatory activities. Statins downregulate the expression of adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MAC-1) and lymphocyte function-associated antigen-1 (LFA-1), on leucocytes and endothelial cells and, through binding to LFA-1, interfere with ICAM-1-LFA-1 interaction, which is crucial for activation of lymphocytes by antigen-presenting cells, ingress of leucocytes into the inflammation sites and immunologic cytotoxicity. Statins inhibit the inducible expression of major histocompatibility complex class II in several cell types including macrophages and downregulate the expression of T-helper-1 (Th1) chemokine receptors on T cells, leading further to inhibition of activation of lymphocytes and their infiltration into the inflammation sites. Statins block the induction of inducible nitric oxide synthase and the expression of several proinflammatory cytokines such as tumour necrosis factor-alpha and interferon-gamma in macrophages and possess antioxidant effects. These agents inhibit the proliferation of immunocytes and the activation of natural killer cells. Regarding the above facts and in view of their safety and inexpensiveness, statins may prove invaluable in the treatment of a multiplicity of dermatologic disorders, especially those characterized by ingress of activated leucocytes into the skin, such as alopecia areata, vitiligo, lichen planus, subacute cutaneous lupus erythematosus, erythema multiforme, psoriasis, bullous pemphigoid, systemic sclerosis, mycosis fungoides, toxic epidermal necrolysis and Behcet's disease.

Clinical Pattern of Bullous Disorders in Eastern Libya.

PubMed

Kanwar, A T; Singh, M; Ei-Mangoush, I M; Bharija, S C; Belhaj, M S

1987-01-01

A retrospective clinical analysis of 66 patients with various bullous disorders seen over a period of 5 years in Benghazi, Libya showed that pemphigus vulgaris was the commonest disorder followed by buuous' petaphigoid. Other bullous dermatoses were rare. The clinical picture and treatment schedule with follow up of some patient is presented.

Clinical and demographic overlaps among immunologically mediated oral diseases: a challenge for clinicians.

PubMed

do Carmo, Maria Auxiliadora Vieira; Gleber-Netto, Frederico Omar; Romano, Maria Luisa de Freitas; Caldeira, Patricia Carlos; de Aguiar, Maria Cassia Ferreira

2014-01-01

This study sought to assess and compare retrospective demographic and clinical data of oral lesions of lichen planus, pemphigus vulgaris, and mucous membrane pemphigoid from the records of the Department of Oral Pathology and Surgery, School of Dentistry, Universidade Federal de Minas Gerais, Brazil, covering a period of 55 years. Out of 25,435 specimens, these immunologically-mediated diseases accounted for 301 (1.18%) cases, of which 250 (0.98%) were lichen planus, 27 (0.11%) were pemphigus vulgaris, and 24 (0.09%) were mucous membrane pemphigoid. Lichen planus presented mainly as white asymptomatic plaques on buccal mucosa. Pemphigus vulgaris was usually characterized by multiple symptomatic erithematous ulcers on the buccal mucosa. Painful ulcers and/or blisters on the gingiva were the most common presentation for mucous membrane pemphigoid. Desquamative gingivitis was noted for all 3 diseases, but mainly for mucous membrane pemphigoid. Overall, lesions were more frequent in white women >50 years. Oral manifestations of immunologically-mediated diseases are relatively rare, and the correct diagnosis can be a challenge for dentists as the lesions often share similar clinical and demographic features.

Bullous Pyoderma Gangrenosum With Subungual Involvement Associated With Ulcerative Colitis.

PubMed

Aktaş Karabay, Ezgi; Aksu Cerman, Aslı; Kıvanc Altunay, İlknur; Yalçın, Özben

2017-06-01

Pyoderma gangrenosum (PG) is a rare inflammatory and ulcerative skin disease of unknown etiology characterized by neutrophilic infiltration of the dermis, mainly affecting the lower extremities. Bullous PG is a rare variant of this disease, usually associated with hematologic disorders. Here, we report a case of pathergy-positive bullous PG with subungual involvement associated with ulcerative colitis.

Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment*

PubMed Central

Clarindo, Marcos Vinícius; Possebon, Adriana Tomazzoni; Soligo, Emylle Marlene; Uyeda, Hirofumi; Ruaro, Roseli Terezinha; Empinotti, Julio Cesar

2014-01-01

Researches on DH have shown that it is not just a bullous skin disease, but a cutaneous-intestinal disorder caused by hypersensitivity to gluten. Exposure to gluten is the starting point of an inflammatory cascade capable of forming autoantibodies that are brought to the skin, where they are deposited, culminating in the formation of skin lesions. These lesions are vesico-bullous, pruritic, and localized especially on elbows, knees and buttocks, although atypical presentations can occur. Immunofluorescence of perilesional area is considered the gold standard for diagnosis, but serological tests help in cases where it is negative. Patients who follow glutenfree diets have better control of symptoms on the skin and intestine, as well as lower risks of progression to lymphoma. Dapsone remains the main drug for treatment, but it requires monitoring of possible side effects, some potentially lethal. PMID:25387490

Unusual presentation of childhood Systemic Lupus Erythematosus

PubMed Central

Kumar, Sathish; Agarwal, Indira

2007-01-01

Bullous systemic lupus erythematosus is a rare blistering condition with a distinctive combination of clinical, histological and immunopathologic features that together constitute a unique bullous disease phenotype. It is often associated with autoimmunity to type VII collagen. Here we report a child who presented with bullous systemic lupus erythematosus. Rapid resolution of the blisters occurred following treatment with dapsone. PMID:18028550

Chinese version of the treatment of autoimmune bullous disease quality of life questionnaire: Reliability and validity.

PubMed

Chen, Guo; Yang, Baoqi; Zhang, Zhaoxia; Yang, Qing; Yan, Xiaoxiao; Murrell, Dédée F; Zhang, Furen

2018-01-01

Treatments for autoimmune blistering disease carry significant risks of medical complications and can affect the patient's quality of life. Recently, the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire was developed in Australia. The objective of this study was to evaluate the reliability and validity of the Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire in Chinese patients with autoimmune blistering diseases. The Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire was produced by forward-backward translation and cross-cultural adaptation of the original English version. Autoimmune blistering disease patients recruited in the study self-administered the Chinese Treatment of Autoimmune Bullous Disease Quality of Life questionnaire, the Dermatology Life Quality Index and the 36-item Short-Form Health Survey. Reliability of the Chinese Treatment of Autoimmune Bullous Disease Quality of Life was evaluated using internal consistency and test-retest (days 0 and 7) methods. Validity was analyzed by face, content, construct, convergent and discriminant validity measures. A total of 86 autoimmune blistering disease patients were recruited for the study. Cronbach's alpha coefficient was 0.883 and the intraclass correlation coefficient was 0.871. Face and content validities were satisfactory. Convergent validity testing revealed correlation coefficients of 0.664 for the Treatment of Autoimmune Bullous Disease Quality of Life and Dermatology Life Quality Index and -0.577 for the Treatment of Autoimmune Bullous Disease Quality of Life and 36-item Short-Form Health Survey. With respect to discriminant validity, no significant differences were observed in the Treatment of Autoimmune Bullous Disease Quality of Life scores of men and women (t = 0.251, P = 0.802), inpatients and outpatients (t = 0.447, P = 0.656), patients on steroids and steroid-sparing medications (t = 0.672, P = 0.503) and patients with different autoimmune blistering disease subtypes (F = 0.030, P = 0.971). Illiterate patients were excluded from the study. The patients were from a single hospital and most of their conditions were in a relatively stable status. The Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire is a reliable and valid instrument to measure treatment burden and to serve as an end point in clinical trials in Chinese autoimmune blistering disease patients.

Case Report: Bullous Scabies in Two Children below 10 Years.

PubMed

Luo, Ze-Yu; Zeng, Mei; Gao, Qian; Zhao, Yu-Kun; Sarkar, Rashmi; Liao, Shu-Ping; Luo, Di-Qing

2017-12-01

Bullous scabies is an infrequent and atypical presentation of scabies, with predilection for elderly and males. Its median age of presentation is 70 years. We report two male cases of bullous scabies who were 7 years and 6 months old. Both patients had excellent response to sulfur 10% ointment alone and have had no recurrence in more than 3 months of follow-up.

Mechanobiological dysregulation of the epidermis and dermis in skin disorders and in degeneration

PubMed Central

Ogawa, Rei; Hsu, Chao-Kai

2013-01-01

During growth and development, the skin expands to cover the growing skeleton and soft tissues by constantly responding to the intrinsic forces of underlying skeletal growth as well as to the extrinsic mechanical forces from body movements and external supports. Mechanical forces can be perceived by two types of skin receptors: (1) cellular mechanoreceptors/mechanosensors, such as the cytoskeleton, cell adhesion molecules and mechanosensitive (MS) ion channels, and (2) sensory nerve fibres that produce the somatic sensation of mechanical force. Skin disorders in which there is an abnormality of collagen [e.g. Ehlers–Danlos syndrome (EDS)] or elastic (e.g. cutis laxa) fibres or a malfunction of cutaneous nerve fibres (e.g. neurofibroma, leprosy and diabetes mellitus) are also characterized to some extent by deficiencies in mechanobiological processes. Recent studies have shown that mechanotransduction is crucial for skin development, especially hemidesmosome maturation, which implies that the pathogenesis of skin disorders such as bullous pemphigoid is related to skin mechanobiology. Similarly, autoimmune diseases, including scleroderma and mixed connective tissue disease, and pathological scarring in the form of keloids and hypertrophic scars would seem to be clearly associated with the mechanobiological dysfunction of the skin. Finally, skin ageing can also be considered as a degenerative process associated with mechanobiological dysfunction. Clinically, a therapeutic strategy involving mechanoreceptors or MS nociceptor inhibition or acceleration together with a reduction or augmentation in the relevant mechanical forces is likely to be successful. The development of novel approaches such as these will allow the treatment of a broad range of cutaneous diseases. PMID:23672502

Clinical implications of aging skin: cutaneous disorders in the elderly.

PubMed

Farage, Miranda A; Miller, Kenneth W; Berardesca, Enzo; Maibach, Howard I

2009-01-01

Aging skin undergoes progressive degenerative change. Structural and physiologic changes that occur as a natural consequence of intrinsic aging combined with the effects of a lifetime of ongoing cumulative extrinsic damage and environment insult (e.g. overexposure to solar radiation) can produce a marked susceptibility to dermatologic disorders in the elderly. As skin ages, the vasculature progressively atrophies. The supporting dermis also deteriorates, with collagen and elastin fibers becoming sparse and increasingly disordered. These changes leave the elderly increasingly susceptible to both vascular disorders such as stasis dermatitis and skin injuries such as pressure ulcers and skin tears, with a steadily decreasing ability to effect skin repair. A parallel erosion of normal immune function produces higher levels of autoimmune skin disorders such as bullous pemphigoid, benign mucous membrane pemphigoid, paraneoplastic pemphigoid, and pemphigus vulgaris. Lichen sclerosus, an autoimmune disorder often occurring in the genital area in older women, is not common but is an important development because of the potential for substantial discomfort as well as serious complications. The prevalence of polypharmacy in this population increases the risk for autoimmune drug reactions, and diagnosis should be undertaken with an awareness that polypharmacy in this population creates a greatly increased susceptibility to drug eruptions that can mimic other cutaneous disorders. Immunologic senescence in the elderly also sets the stage for potential reactivation of the Varicella zoster virus, in which initial dermatologic involvement expands into the major sensory ganglia. Known as shingles, this disorder can be excruciatingly painful with the potential to cause blindness if the optic nerve becomes involved. Dermatoses such as xerosis, pruritus, and eczema are also widespread in the elderly, create substantial suffering in those afflicted, and often prove recalcitrant to treatment. Individual susceptibility to specific types of contact dermatitis changes over the lifetime, and seborrheic dermatitis is substantially more prevalent in the elderly. It is not uncommon for older patients to have multiple impairments, with the potential for cognitive dysfunction as well as impaired vision, hearing, or mobility. In addition, they may not have adequate housing or nutrition, or the financial resources necessary for adequate compliance. Physicians must take into consideration the patient's physical ability to comply with the recommended therapy as well as socioeconomic factors that may impact on compliance. Simple topical regimens are preferable wherever possible in order to maximize compliance and, therefore, efficacy. Extra effort may be necessary to ensure that instructions are accurately followed and that ongoing compliance with the regimen prescribed is actually achieved. Management of dermatologic disorders in the elderly is often less than optimal, due to the fact that the special needs and limitations of this population are not adequately considered. Treatments should consider the intrinsic differences between younger and older patients that may impact on diagnosis and therapy choice. The aged patient is often afflicted with numerous co-morbidities that can influence the choice of therapy. Skin integrity in the elderly is compromised, and safety concerns are increased with the long-term use of any medication prescribed. In addition, the prevalence of polypharmacy in the aged population substantially increases the risk of cutaneous drug reactions, which can profoundly complicate accurate diagnosis of dermatologic disorders. The aged population also needs to be more closely monitored because of increased fragility of the skin and the physical limitations that may hinder compliance with prescribed regimens.

Outbreak of staphylococcal bullous impetigo in a maternity ward linked to an asymptomatic healthcare worker.

PubMed

Occelli, P; Blanie, M; Sanchez, R; Vigier, D; Dauwalder, O; Darwiche, A; Provenzano, B; Dumartin, C; Parneix, P; Venier, A G

2007-11-01

An outbreak of staphylococcal bullous impetigo occurred over a period of five months in a maternity ward involving seven infected and two colonised neonates. The skin lesions were due to epidermolytic toxin A-producing Staphylococcus aureus. Infection control measures were implemented and a retrospective case-control study performed. Contact with an auxiliary nurse was the only risk factor for cases of bullous impetigo (P<0.01). The nurse cared for all seven cases and was an asymptomatic nasal carrier of the epidemic strain. Repeated courses of decontamination treatment failed to eradicate carriage. Nine months after the last case, another neonate developed a more severe form of bullous impetigo and the auxiliary nurse was reassigned to an adult ward.

The Use of Intralesional Steroids in a Case of Localized Pemphigus Foliaceus

PubMed Central

Ghoneim, Sara; Zaiac, Martin

2017-01-01

A 37-year-old South-Asian male presented to our clinic with a crusty, verrucous-like, scaly plaque of the left ala of the nose. After ruling out infectious and other epidermal bullous diseases, we finalized a diagnosis of localized pemphigus foliaceus, an exceptionally rare disorder with only 15 cases reported in the literature to date. The hyperkeratotic lesions responded favorably to a 3-week regimen of triamcinolone ointment and a onetime intralesional triamcinolone 2.5 mg/mL injection. PMID:28868007

[Ocular cicatricial pemphigoid - state of the art in clinic and therapy for a problematic disease].

PubMed

Rübsam, A; Klein, J P; Pleyer, U

2013-08-01

The ocular cicatricial pemphigoid (OCP) belongs to a family of chronically progressive autoimmune disorders, predominantly affecting mucous membranes (mucous membrane pemphigoids). It is an immunopathologically heterogeneous group of disorders with variable phenotypes that share the unique feature of a subepidermal blistering, through disruption of the adhesion between epidermis and dermis. A key feature is the chronically active inflammation with consecutive fibrosis, leading to a partial or complete loss of function of the affected organ. The ocular disease as a chronic cicatrising conjunctivitis is a common manifestation of the mucous membrane pemphigoid. The identification of the subtle pathology and the prompt initiation of an appropriate therapy are of pivotal importance. One purpose is to prevent further vision loss due to extensive corneal scarring and life-threatening systemic complications, such as the formation of oesophageal or tracheal strictures. So far there are no prospective, randomised studies, regarding the therapy guidelines with an evidence level more than III. The autoimmune nature of the disease implies that systemic immunosuppression is the only effective treatment option, most notably in extended stages. The aim of our study is to give a guideline for a stage adjusted therapy with conventional immunosuppressants and to give a perspective for alternative therapies, especially for recalcitrant disease. Georg Thieme Verlag KG Stuttgart · New York.

Successful treatment of bullous lichen planus with acitretin monotherapy. Review of treatment options for bullous lichen planus and case report.

PubMed

Rallis, Efstathios; Liakopoulou, Angeliki; Christodoulopoulos, Constantinos; Katoulis, Alexandros

2016-12-31

Bullous lichen planus (BLP) is a rare variant of lichen planus, characterized by the development of vesicular and bullous lesions, of skin, nails, hair and/or mucosa. We present a case of 63-year-old woman with BLP, unresponsive to previous therapies with topical corticosteroids, topical calcipotriol, antihistamines and oral cyclosporine (4 mg/kg/day for 4 months). She was already receiving treatment for arterial hypertension, hyperlipidemia, atrial fibrillation and uncontrolled diabetes mellitus. Acitretin was administered for 5 months with complete remission of BLP lesions and no major side effects. This is probably the first reported case of BLP treated with acitretin monotherapy. In this case acitretin was an efficacious and well-tolerated therapeutic option for BLP.

The importance of direct immunofluorescence in pemphigus herpetiformis diagnosis*

PubMed Central

de Faria, Paula Carolina Pessanha; Cruz, Camila Caberlon; Abulafia, Luna Azulay; Maceira, Juan Manuel Pineiro; Cassia, Flávia de Freire; Medeiros, Paula Mota

2017-01-01

Pemphigus herpetiformis is an autoimmune bullous disease, that combines clinical features of dermatitis herpetiformis and linear IgA bullous dermatosis and immunological characteristics of pemphigus, which makes this disease peculiar and this diagnosis rarely suspected in the first evaluation of the patient. The reported case is of a patient with clinically bullous disease similar to dermatitis herpetiformis, whose multiple biopsies were inconclusive, and only after direct immunofluorescence with a pemphigus pattern (intraepidermal intercellular pattern) the confirmation of the diagnosis was possible. PMID:29267475

[Management of corneal endothelial decompensation with Descemet's membrane endothelial keratoplasty in a patient with Ahmed glaucoma valve implant].

PubMed

Röck, T; Bartz-Schmidt, K-U; Röck, D; Yoeruek, E

2014-05-01

Currently, the main causes for developing bullous keratopathy are from problems related to intraocular surgery, trauma, infection, Fuchs' endothelial dystrophy and chronically elevated intraocular pressure. In the 1990s penetrating keratoplasty was once considered the therapy of choice for treatment of bullous keratopathy but in recent years it has been replaced by posterior lamellar keratoplasty. The Descemet membrane endothelial keratoplasty (DMEK) procedure represents the final development of posterior lamellar keratoplasty. The question now arises whether DMEK can be used in patients with bullous keratopathy and Ahmed glaucoma valve implant. A 72-year-old man was referred to our hospital for further evaluation with the diagnosis of bullous keratopathy and pseudoexfoliative glaucoma. The bullous keratopathy was caused by a variety of previous operations as well as decompensation of intraocular pressure. This article describes the therapy of bullous keratopathy by DMEK with existing Ahmed glaucoma valve implant. After surgery the cornea became clear and the best-corrected visual acuity improved from hand movement to 0.2. The intraocular pressure remained normal (10-14 mmHg) without antiglaucoma medication and the endothelial cell count decreased only slightly over a follow-up of 13 months. No complications were encountered. The DMEK surgical procedure seems to be possible in patients with Ahmed glaucoma valve implant and endothelial decompensation. However, further studies with a larger number of patients should follow to validate the replacement of penetrating keratoplasty and other posterior lamellar procedures by DMEK.

The Structure of the Plakin Domain of Plectin Reveals an Extended Rod-like Shape*

PubMed Central

Carballido, Ana M.

2016-01-01

Plakins are large multi-domain proteins that interconnect cytoskeletal structures. Plectin is a prototypical plakin that tethers intermediate filaments to membrane-associated complexes. Most plakins contain a plakin domain formed by up to nine spectrin repeats (SR1–SR9) and an SH3 domain. The plakin domains of plectin and other plakins harbor binding sites for junctional proteins. We have combined x-ray crystallography with small angle x-ray scattering (SAXS) to elucidate the structure of the plakin domain of plectin, extending our previous analysis of the SR1 to SR5 region. Two crystal structures of the SR5-SR6 region allowed us to characterize its uniquely wide inter-repeat conformational variability. We also report the crystal structures of the SR7-SR8 region, refined to 1.8 Å, and the SR7–SR9 at lower resolution. The SR7–SR9 region, which is conserved in all other plakin domains, forms a rigid segment stabilized by uniquely extensive inter-repeat contacts mediated by unusually long helices in SR8 and SR9. Using SAXS we show that in solution the SR3–SR6 and SR7–SR9 regions are rod-like segments and that SR3–SR9 of plectin has an extended shape with a small central kink. Other plakins, such as bullous pemphigoid antigen 1 and microtubule and actin cross-linking factor 1, are likely to have similar extended plakin domains. In contrast, desmoplakin has a two-segment structure with a central flexible hinge. The continuous versus segmented structures of the plakin domains of plectin and desmoplakin give insight into how different plakins might respond to tension and transmit mechanical signals. PMID:27413182

Forty-five years of keratoprosthesis study and application at the Filatov Institute: a retrospective analysis of 1 060 cases

PubMed Central

Iakymenko, Stanislav

2013-01-01

AIM To present results of the keratoprosthesis method used at The Filatov Institute of Eye Diseases and Tissue Therapy. METHODS A retrospective case series analysis was used to describe the development of new types of keratoprostheses and methods of implantation as well as different ways of leukoma strengthening. RESULTS Keratoprosthesis was performed in 1 060 eyes of 1 040 patients with leukomas of different etiology: burns, 725 eyes (68.4%); trauma, 120 eyes (11.3%); keratitis and ocular pemphigoid, 108 eyes (10.2%); and bullous keratopathy, 107 eyes (10.1%). Visual acuity before keratoprosthesis consisted of light perception in 962 eyes (92%), and 98 eyes (8%) had minimal visual acuity (1/200-1/50). Both eyes were blind (visual acuity less than 1/200) in 955 patients (91.8%). The period of blindness varied from 1 to 52 years. As a result of keratoprosthesis, visual acuity of ≥1/200 was restored in 1 023 of 1 060 eyes (96.5%). Visual acuity of 20/200-20/20 was achieved in 716 eyes (67.5%). At the last follow-up visit visual acuity of ≥1/200 was preserved in 806 eyes (76%), visual acuity of 20/200-20/20 was measured in 583 of 1 060 eyes (55%) and good keratoprosthesis fixation in the cornea was achieved in 986 of 1 060 eyes (93%). The minimal follow-up was 12 months (range, 12 months to 37 years, median 5 years). CONCLUSION Our techniques of keratoprosthesis effectively restore vision in patients with leukomas that cannot be treated by optical corneal grafting. PMID:23826536

Analysis of Serum Cytokine Profile in Pemphigus.

PubMed

Lee, Sang Hee; Hong, Won Jin; Kim, Soo-Chan

2017-08-01

Pemphigus is a group of autoimmune blistering diseases affecting skin and mucous membranes. While pemphigus is an autoantibody mediated disease, the role of T cells and cytokines in the pathogenesis is being increasingly recognized. This study was conducted to observe alterations in the serum cytokine levels of patients with pemphigus vulgaris (PV), pemphigus foliaceous (PF), paraneoplastic pemphigus (PNP) and compare with bullous pemphigoid (BP) and healthy subjects. A total of 75 subjects (28 PV, 13 PF, 7 PNP, 7 BP, and 20 healthy controls) were included, all patients in active disease state. Serum levels of interferon (IFN)-γ, interleukin (IL)-4, IL-6, IL-17A, IL-10, tumor necrosis factor (TNF)-α, and IL-8 were measured by enzyme-linked immunosorbent assay. The median concentration of IFN-γ was lower in PV and BP patients compared to control (0.77, 0.34 and 1.63 pg/ml, respectively). IL-6 and IL-10 was significantly higher in PNP patients compared to control (4.92 and 0.24 pg/ml for IL-6, 0.86 and <0.12 pg/ml for IL-10, respectively). IL-8 was increased significantly in PV and PNP patients compared with control (11.85, 31.5 and 8.31 pg/ml, respectively). For IL-4, IL-17A and TNF-α, no significant difference was observed between the five groups. The decreased level of IFN-γ in PV may imply suppressed Th1 response in the active disease stage. A Th2 predominant response is suggested in the active stage of PNP, with elevated serum levels of IL-6 and IL-10. Increased level of proinflammatory cytokine IL-8 is observed in the sera of PV and PNP patients.

Collagen XVII (BP180) modulates keratinocyte expression of the proinflammatory chemokine, IL-8.

PubMed

Van den Bergh, Françoise; Eliason, Steven L; Burmeister, Brian T; Giudice, George J

2012-08-01

Collagen XVII (COL17), a transmembrane protein expressed in epidermal keratinocytes (EK), is targeted by pathogenic autoantibodies in bullous pemphigoid. Treatment of EK with anti-COL17 autoantibodies triggers the production of proinflammatory cytokines. In this study, we test the hypothesis that COL17 is involved in the regulation of the EK proinflammatory response, using IL-8 expression as the primary readout. The absence of COL17 in EK derived from a junctional epidermolysis bullosa patient or shRNA-mediated knockdown of COL17 in normal EK resulted in a dysregulation of IL-8 responses under various conditions. The COL17-deficient cells showed an abnormally high IL-8 response after treatment with lipopolysaccharide (LPS), ultraviolet-B radiation or tumor necrosis factor, but exhibited a blunted IL-8 response to phorbol 12-myristate 13-acetate exposure. Induction of COL17 expression in COL17-negative EK led to a normalization of the LPS-induced proinflammatory response. Although α6β4 integrin was found to be up-regulated in COL17-deficient EK, siRNA-mediated knockdown of the α6 and β4 subunits revealed that COL17's effects on the LPS IL-8 response are not dependent on this integrin. In LPS-treated cells, inhibition of NF-kappa B activity in COL17-negative EK resulted in a normalization of their IL-8 response, and expression of an NF-kappa B-driven reporter was shown to be higher in COL17-deficient, compared with normal EK. These findings support the hypothesis that COL17 plays an important regulatory role in the EK proinflammatory response, acting largely via NF-kappa B. Future investigations will focus on further defining the molecular basis of this novel control network. © 2012 John Wiley & Sons A/S.

Collagen XVII (BP180) Modulates Keratinocyte Expression of the Proinflammatory Chemokine, IL-8

PubMed Central

Van den Bergh, Françoise; Eliason, Steven L.; Burmeister, Brian T.; Giudice, George J.

2012-01-01

Collagen XVII (COL17), a transmembrane protein expressed in epidermal keratinocytes (EK), is targeted by pathogenic autoantibodies in bullous pemphigoid. Treatment of EK with anti-COL17 autoantibodies triggers the production of proinflammatory cytokines. In this paper we test the hypothesis that COL17 is involved in the regulation of the EK proinflammatory response, using IL-8 expression as the primary readout. The absence of COL17 in EK derived from a junctional epidermolysis bullosa patient or shRNA-mediated knockdown of COL17 in normal EK resulted in a dysregulation of IL-8 responses under various conditions. The COL17-deficient cells showed an abnormally high IL-8 response after treatment with lipopolysaccharide (LPS), ultraviolet-B radiation or tumor necrosis factor, but exhibited a blunted IL-8 response to phorbol 12-myristate 13-acetate exposure. Induction of COL17 expression in COL17-negative EK led to a normalization of the LPS-induced proinflammatory response. Although α6β4 integrin was found to be up-regulated in COL17-deficient EK, siRNA-mediated knockdown of the α6 and β4 subunits revealed that COL17’s effects on the LPS IL-8 response are not dependent on this integrin. In LPS-treated cells, inhibition of NF-kappa B activity in COL17-negative EK resulted in a normalization of their IL-8 response, and expression of an NF-kappa B-driven reporter was shown to be higher in COL17-deficient, compared with normal, EK. These findings support the hypothesis that COL17 plays an important regulatory role in the EK proinflammatory response, acting largely via NF-kappa B. Future investigations will focus on further defining the molecular basis of this novel control network. PMID:22775995

Analysis of Serum Cytokine Profile in Pemphigus

PubMed Central

Lee, Sang Hee; Hong, Won Jin

2017-01-01

Background Pemphigus is a group of autoimmune blistering diseases affecting skin and mucous membranes. While pemphigus is an autoantibody mediated disease, the role of T cells and cytokines in the pathogenesis is being increasingly recognized. Objective This study was conducted to observe alterations in the serum cytokine levels of patients with pemphigus vulgaris (PV), pemphigus foliaceous (PF), paraneoplastic pemphigus (PNP) and compare with bullous pemphigoid (BP) and healthy subjects. Methods A total of 75 subjects (28 PV, 13 PF, 7 PNP, 7 BP, and 20 healthy controls) were included, all patients in active disease state. Serum levels of interferon (IFN)-γ, interleukin (IL)-4, IL-6, IL-17A, IL-10, tumor necrosis factor (TNF)-α, and IL-8 were measured by enzyme-linked immunosorbent assay. Results The median concentration of IFN-γ was lower in PV and BP patients compared to control (0.77, 0.34 and 1.63 pg/ml, respectively). IL-6 and IL-10 was significantly higher in PNP patients compared to control (4.92 and 0.24 pg/ml for IL-6, 0.86 and <0.12 pg/ml for IL-10, respectively). IL-8 was increased significantly in PV and PNP patients compared with control (11.85, 31.5 and 8.31 pg/ml, respectively). For IL-4, IL-17A and TNF-α, no significant difference was observed between the five groups. Conclusion The decreased level of IFN-γ in PV may imply suppressed Th1 response in the active disease stage. A Th2 predominant response is suggested in the active stage of PNP, with elevated serum levels of IL-6 and IL-10. Increased level of proinflammatory cytokine IL-8 is observed in the sera of PV and PNP patients. PMID:28761292

CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis.

PubMed

Pender, Michael P

2012-01-01

CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV) infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1) CD8+ T-cell deficiency, (2) primary EBV infection, (3) decreased CD8+ T-cell control of EBV, (4) increased EBV load and increased anti-EBV antibodies, (5) EBV infection in the target organ, (6) clonal expansion of EBV-infected autoreactive B cells in the target organ, (7) infiltration of autoreactive T cells into the target organ, and (8) development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.

CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis

PubMed Central

Pender, Michael P.

2012-01-01

CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV) infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1) CD8+ T-cell deficiency, (2) primary EBV infection, (3) decreased CD8+ T-cell control of EBV, (4) increased EBV load and increased anti-EBV antibodies, (5) EBV infection in the target organ, (6) clonal expansion of EBV-infected autoreactive B cells in the target organ, (7) infiltration of autoreactive T cells into the target organ, and (8) development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection. PMID:22312480

Human autoantibodies against a desmosomal core protein in pemphigus foliaceus

PubMed Central

1984-01-01

Pemphigus foliaceus (PF) is a human autoimmune disease in which antibodies are directed against the cell surface of epidermal cells with resultant blister formation. The histopathology of these blisters indicates that cells have detached from each other, and electron microscopy of early blisters shows diminished numbers, to complete loss, of desmosomes as well as abnormalities of the tonofilament- desmosome complex. In this study we demonstrate that autoantibodies from certain PF patients bind to a desmosomal core glycoprotein called desmoglein (DG) I. Proteins in extracts of normal human epidermis were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE), then transferred to nitrocellulose or 2- aminophenylthioether paper for immunoperoxidase staining. Results of these immunoblots indicated that sera from 6 of 13 PF patients specifically and intensely stained an approximately 160,000 mol wt polypeptide, "PF antigen". Such staining was not seen with normal human sera or sera from patients with pemphigus vulgaris or bullous pemphigoid, two autoimmune blistering skin diseases that are clinically, histologically, and immunochemically distinct from PF. However, rabbit antiserum directed against DGI, that was isolated from bovine muzzle desmosomes, stained a polypeptide band which co-migrated with PF antigen. Furthermore, when proteins from extracts of normal human epidermis were electrophoresed in two dimensions (isoelectric focusing, then SDS-PAGE) before transfer to nitrocellulose for immunoperoxidase staining, PF antibodies and antibodies to DGI stained identical spots. Finally, PF sera as well as PF IgG that was affinity purified with PF antigen from normal human epidermis, both selectively bound to DGI extracted from bovine muzzle desmosomes. These studies demonstrate that the human autoantibodies from certain patients with PF, a disease of epidermal cell adhesion, are directed against a desmosomal core protein. PMID:6491602

Vesiculo-Bullous Disorders of the Neonate

PubMed Central

McKay, Roberta M.

1987-01-01

This is the first of three articles which outline the diagnoses to be considered when vesiculo-bullous lesions are identified in the neonate, children, and adults. This paper presents a brief sketch of blistering disorders which may occur during the first few weeks of life. Vesiculo-bullous lesions in the neonate may represent benign, infectious, genetic, or life-threatening disorders. Early recognition, appropriate diagnostic procedures, and specific therapeutic interventions can be vital in reducing potential morbidity and mortality. General guidelines for diagnostic procedures and therapeutic interventions are discussed, along with some of the newer etiologic and epidemiologic concepts. PMID:21263952

Childhood-onset bullous systemic lupus erythematosus.

PubMed

Lourenço, D M R; Gomes, R Cunha; Aikawa, N E; Campos, L M A; Romiti, R; Silva, C A

2014-11-01

Bullous systemic lupus erythematosus has rarely been described in pediatric lupus population and the real prevalence of childhood-onset bullous systemic lupus erythematosus has not been reported. From January 1983 to November 2013, 303 childhood-onset SLE (c-SLE) patients were followed at the Pediatric Rheumatology Unit of the Childreńs Institute of Hospital das Clínicas da Faculdade de Medicina Universidade da Universidade de São Paulo, three of them (1%) diagnosed as childhood-onset bullous systemic lupus erythematosus. All three cases presented tense vesiculobullous lesions unassociated with lupus erythematosus lesions, with the median duration of 60 days (30-60). All patients fulfilled bullous systemic lupus erythematosus criteria. Two had nephritis and serositis and presented specific autoantibodies. The histological pattern demonstrated subepidermal blisters with neutrophils-predominant infiltrates within the upper dermis. Direct immunofluorescence (DIF) showed deposits of IgG and complement along the epidermal basement membrane, in the presence or absence of IgA and/or IgM. A positive indirect immunofluorescence on salt-split skin demonstrating dermal binding was observed in two cases. All of them had moderate/severe disease activity at diagnosis with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 18 (14-24). Two patients received dapsone and one with severe nephritis received immunosuppressive drugs. In conclusion, in the last 30 years the prevalence of bullous lupus in childhood-onset lupus population was low (1%) in our tertiary University Hospital. A diagnosis of SLE should always be considered in children with recurrent tense vesiculobullous lesions with or without systemic manifestations. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Bullous reactions to bed bug bites reflect cutaneous vasculitis

USDA-ARS?s Scientific Manuscript database

This study evaluates bullous cutaneous reactions and sequential histopathology in an individual sensitized to bed bug bites in an effort to better understand the allergic response and histology associated with these bites. There was a progression of the inflammatory response across time ranging from...

Bullous dermatitis artefacta.

PubMed

Sokumbi, Olayemi; Comfere, Nneka I; McEvoy, Marian T; Peters, Margot S

2013-02-01

Bullous artefactual dermatoses are rare and may be induced by various techniques, including chemicals, heat, or electrical current. Proving a factitial etiology and identifying the mechanism of injury may be difficult. We describe the clinical features and histopathology of 2 patients with bullous disease induced by electrical current or heat. Physical examination in both patients demonstrated geometrically shaped tense bullae. Skin biopsies revealed epidermal necrosis overlying a pauci-inflammatory subepidermal cleft, with homogenization of underlying superficial dermal collagen. In 1 of the 2 patients, there was prominent vertical elongation of keratinocyte nuclei and also of cytoplasmic processes. Direct immunofluorescence study of skin plus testing of serum by indirect immunofluorescence and enzyme-linked immunosorbent assay for BP180 and BP230 antibodies revealed no evidence for immunobullous disease in either patient. Vertical elongation of keratinocyte nuclei, often attributed to a polarization effect of electrical current, is characteristic of electrical burn but also may be induced by thermal injury. These 2 patients highlight the importance of histopathology in confirming a diagnosis of bullous dermatitis artefacta.

Bullous Complex Regional Pain Syndrome: A description of the clinical and histopathologic features.

PubMed

Ho, J D; Al-Haseni; Smith, S; Bhawan, J; Sahni, D

2018-04-27

Complex regional pain syndrome (CRPS, formerly reflex sympathetic dystrophy) is a poorly understood syndrome occurring most commonly after peripheral trauma.(1) Diagnostic features include pain, autonomic dysregulation, sensory/motor abnormalities and trophic changes involving the affected limb.(1,2) Dermatologic findings include erythema, atrophy, xerosis, erosive disease, and reticulated erythematous patches.(3,4) Exceptionally, blistering has been reported.(5-7) Given its rarity, the clinical and histopathologic findings of bullous CRPS are not well described. We report a case of bullous CRPS in a patient with mycosis fungoides (MF), describing the clinical and histopathologic features of this uncommon entity. This article is protected by copyright. All rights reserved.

Development of a quality-of-life instrument for autoimmune bullous disease: the Autoimmune Bullous Disease Quality of Life questionnaire.

PubMed

Sebaratnam, Deshan F; Hanna, Anna Marie; Chee, Shien-ning; Frew, John W; Venugopal, Supriya S; Daniel, Benjamin S; Martin, Linda K; Rhodes, Lesley M; Tan, Jeremy Choon Kai; Wang, Charles Qian; Welsh, Belinda; Nijsten, Tamar; Murrell, Dédée F

2013-10-01

Quality-of-life (QOL) evaluation is an increasingly important outcome measure in dermatology, with disease-specific QOL instruments being the most sensitive to changes in disease status. To develop a QOL instrument specific to autoimmune bullous disease (AIBD). A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL before factor analysis was performed to yield the final ABQOL questionnaire of 17 questions. We evaluated validity and reliability across a range of indices. Australian dermatology outpatient clinics and private dermatology practices. PATIENTS AND EXPOSURE: Patients with a histological diagnosis of AIBD. The development of an AIBD-specific QOL instrument. Face and content validity were established through the comprehensive patient interview process and expert review. In terms of convergent validity, the ABQOL was found to have a moderate correlation with scores on the Dermatology Life Quality Index (R = 0.63) and the General Health subscale of the 36-Item Short Form Health Survey (R = 0.69; P = .009) and low correlation with the Pemphigus Disease Area Index (R = 0.42) and Autoimmune Bullous Disease Skin Disorder Intensity Score (R = 0.48). In terms of discriminant validity, the ABQOL was found to be more sensitive than the Dermatology Life Quality Index (P = .02). The ABQOL was also found to be a reliable instrument evaluated by internal consistency (Cronbach α coefficient, 0.84) and test-retest reliability (mean percentage variation, 0.92). The ABQOL has been shown to be a valid and reliable instrument that may serve as an end point in clinical trials. Future work should include incorporating patient weighting on questions to further increase content validity and translation of the measure to other languages. anzctr.org.au Identifier: ACTRN12612000750886.

Effect of Glyceraldehyde Cross-Linking on a Rabbit Bullous Keratopathy Model.

PubMed

Wang, Mengmeng

2015-01-01

Background. To evaluate the effects of corneal glyceraldehyde CXL on the rabbit bullous keratopathy models established by descemetorhexis. Methods. Fifteen rabbits were randomly divided into five groups. Group A (n = 3) is the control group. The right eyes of animals in Groups B,C, D, and E (n = 3, resp.) were suffered with descemetorhexis procedures. From the 8th day to the 14th day postoperatively, the right eyes in Groups C and D were instilled with hyperosmolar drops and glyceraldehyde drops, respectively; the right eyes in Group E were instilled with both hyperosmolar drops and glyceraldehyde drops. Central corneal thickness (CCT), corneal transparency score, and histopathological analysis were applied on the eyes in each group. Results. Compared with Group A, statistically significant increase in CCT and corneal transparency score was found in Groups B, C, D, and E at 7 d postoperatively (P < 0.05) and in Groups C, D, and E at 14 d postoperatively (P < 0.05). Conclusion. Chemical CXL technique using glyceraldehyde improved the CCT and corneal transparency of the rabbit bullous keratopathy models. Topical instillation with glyceraldehyde and hyperosmolar solutions seems to be a good choice for the bullous keratopathy treatment.

Oral bullous lichen planus: Case report and review of management

PubMed Central

Patil, Archana; Prasad, Shiva; Ashok, L.; Sujatha, G. P.

2012-01-01

A 34-year-old female patient with the chief complaint of burning sensation in the oral cavity associated with generalized pruritis, scalp and skin lesions diagnosed as Bullous lichen planus and treated with systemic prednisolone, levamisole, benzydamine oral rinse. Patient is in follow up since 1 year and free of lesions. Here we report the case and review current modalities in the management of oral lichen planus. PMID:23293497

Sensitivity and specificity of clinical, histologic, and immunologic features in the diagnosis of paraneoplastic pemphigus.

PubMed

Joly, P; Richard, C; Gilbert, D; Courville, P; Chosidow, O; Roujeau, J C; Beylot-Barry, M; D'incan, M; Martel, P; Lauret, P; Tron, F

2000-10-01

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease characterized by the production of autoantibodies mainly directed against proteins of the plakin family. An overlapping distribution of autoantibody specificities has been recently reported between PNP, pemphigus vulgaris (PV), and pemphigus foliaceus (PF), which suggests a relationship between the different types of pemphigus. Our purpose was to evaluate the sensitivity and the specificity of clinical, histologic, and immunologic features in the diagnosis of PNP. The clinical, histologic, and immunologic features of 22 PNP patients were retrospectively reviewed and compared with those of 81 PV and PF patients without neoplasia and of 8 PV and 4 PF patients with various neoplasms. One clinical and 2 biologic features had both high sensitivity (82%-86%) and high specificity (83%-100%) whatever the control group considered: (1) association with a lymphoproliferative disorder, (2) indirect immunofluorescence (IIF) labeling of rat bladder, and (3) recognition of the envoplakin and/or periplakin bands in immunoblotting. Two clinicopathologic and two biologic features had high specificity (87%-100%) but poor sensitivity (27%-59%): (1) clinical presentation associating erosive oral lesions with erythema multiforme-like, bullous pemphigoid-like, or lichen planus-like cutaneous lesions; (2) histologic picture of suprabasal acantholysis with keratinocyte necrosis, interface changes, or lichenoid infiltrate; (3) presence of both anti-epithelial cell surface and anti-basement membrane zone antibodies by IIF; and (4) recognition of the desmoplakin I and/or BPAG1 bands in immunoblotting. Interestingly, 45% of patients with PNP presented initially with isolated oral erosions that were undistinguishable from those seen in PV patients, and 27% had histologic findings of only suprabasal acantholysis, which was in accordance with the frequent detection of anti-desmoglein 3 antibodies in PNP sera. The association with a lymphoproliferative disorder, the IIF labeling of rat bladder, and the immunoblotting recognition of envoplakin and/or periplakin are both sensitive and specific features in the diagnosis of PNP.

Dermatologic Reactions to Immune Checkpoint Inhibitors : Skin Toxicities and Immunotherapy.

PubMed

Sibaud, Vincent

2018-06-01

The development of immune checkpoint inhibitors [monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1)] represents a major breakthrough in cancer therapy. Although they present a favorable risk/benefit ratio, immune checkpoint blockade therapies have a very specific safety profile. Due to their unique mechanism of action, they entail a new spectrum of adverse events that are mostly immune related [immune-related adverse events (irAEs)], notably mediated by the triggering of cytotoxic CD4+/CD8+ T cell activation. Cutaneous toxicities appear to be one of the most prevalent irAEs, both with anti-PD-1 and anti-CTLA-4 agents or with the newly developed anti-PD-L1 agents, which corresponds to a class effect. They are observed in more than one-third of the treated patients, mainly in the form of a maculopapular rash (eczema-like spongiotic dermatitis) and pruritus. A wide range of other dermatologic manifestations can also occur, including lichenoid reactions, psoriasis, acneiform rashes, vitiligo-like lesions, autoimmune skin diseases (e.g., bullous pemphigoid, dermatomyositis, alopecia areata), sarcoidosis or nail and oral mucosal changes. In addition, the use of anti-CTLA-4 and anti-PD-1 therapies in combination is associated with the development of more frequent, more severe and earlier cutaneous irAEs compared to single agents. In most cases, these dysimmune dermatologic adverse events remain self-limiting and readily manageable. Early recognition and adequate management, however, are critical to prevent exacerbation of the lesions, to limit treatment interruption and to minimize quality of life impairment. This review describes the variable clinical and histopathologic aspects of dermatologic irAEs induced by immune checkpoint inhibitors. Appropriate treatment and counseling are also proposed, with a step-by-step approach for optimized management by both practicing oncologists and dermatologists.

[Staphylococcal scalded skin syndrome and bullous impetigo in newborn twins infected by breast milk].

PubMed

Bridier, A; Léauté-Labrèze, C; Lehours, P; Sarlangue, J

2007-10-01

Staphylococcus aureus is often responsible for late septic infections, more rarely of toxinic ones, occurring in neonatal period. We report a case of staphylococcal scalded skin syndrome and bullous impetigo in newborn twins infected by breast milk from their asymptomatic mother. This transmission was confirmed by molecular biology method. This case emphasizes the potential part of the mother in staphylococcal nosocomial infections and the complexity of toxinic mechanisms.

[Kindler syndrome: clinical and ultra-structural particularities, a propos of three cases].

PubMed

El Fekih, Nadia; Mahfoudh, Anis; Zekri, Samy; Kharfi, Monia; Fazaa, Bécima; Jaafoura, Mohamed Habib; Kamoun, Mohamed Ridha

2011-08-01

Kindler's syndrome is a rare type of genetic skin condition belonging to the class of bullous poikilodermia. We report three new sibling cases of this rare syndrome. The condition was seen in three sisters aged 12, 16 and 20 years, born of a first-degree consanguineous marriage with no family history of Kindler's syndrome. The three patients presented spontaneously regressive bullous eruptions, poikilodermia of gradual onset, major cutaneous atrophy on the back of the hands and the feet, photosensitivity and gingival hypertrophy. Electron microscopy examination of poikilodermic skin showed normal anchoring filaments and intraepidermal cleavage. Diagnosis of Kindler's syndrome is based upon clinical evidence. Kidler's syndrome is a well defined clinical entity. Ultra-structural studies show intraepidermal, junctional, and dermal cleavage. This syndrome must be differentiated from congenital epidermolysis bullosa, Weary's syndrome, and other bullous hereditary poikilodermas. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Piperacillin-tazobactam-induced linear IgA bullous dermatosis presenting clinically as Stevens-Johnson syndrome/toxic epidermal necrolysis overlap.

PubMed

Adler, N R; McLean, C A; Aung, A K; Goh, M S Y

2017-04-01

Linear IgA bullous dermatosis (LABD) is a subepidermal autoimmune bullous disease characterized by linear IgA deposition at the basement membrane zone, which is visualized by direct immunofluorescence. Patients with LABD typically present with widespread vesicles and bullae; however, this is not necessarily the case, as the clinical presentation of this disease is heterogeneous. LABD clinically presenting as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) is an infrequent, yet well-described phenomenon. Most cases of LABD are idiopathic, but some cases are drug-induced. Multiple drugs have been implicated in the development of LABD. We report a case of piperacillin-tazobactam-induced LABD presenting clinically as SJS/TEN overlap. This is the first reported case of a strong causal association between piperacillin-tazobactam and the development of LABD. © 2017 British Association of Dermatologists.

Forme particulière de Pemphigoide cicatricielle à dépôt unique d'IgA

PubMed Central

Aounallah, Amina; Jrad, Mariem; Ksiaa, Mehdi; Mokni, Sana; Saidi, Wafa; Boussofara, Lobna; Sriha, Badreddine; Denguezli, Mohamed; Ghariani, Najet; Belajouza, Colandane; Nouira, Rafia

2017-01-01

La Pemphigoide cicatricielle est une dermatose bulleuse sous épithéliale qui atteint essentiellement les muqueuses avec une évolution cicatricielle. Il s'agit d'un homme de 66 ans hospitalisé pour gingivite érosive avec dysphagie, dyspnée et flou visuel. L'examen dermatologique retrouvait des lésions érosives du palais et du pharynx. L'examen ophtalmologique notait des symblépharons, un ectropion et une cataracte bilatérale. La biopsie gingivale avait montré un décollement nécrotique de l'épithélium buccal. L'immunofluorescence directe notait un dépôt linéaire d'Immunoglobuline A à la jonction dermo-épidermique. L'Immunofluorescence indirecte était revenue négative. Le diagnostic de pemphigoide cicatricielle était confirmé. Le Transit oeso-gastro-duodénal a objectivé une double sténose de l'œsophage. L'endoscopie nasale, pharyngée et bronchique retrouvait des ulcérations de l'épiglotte, de l'hypopharynx, du pharynx et de l'arbre bronchique. Le patient a bénéficié d'un bolus de Solumedrol relayé par la Prednisone à la dose de 0.5mg/Kg/j associé à la Disulone à la dose de 100mg/j. L'évolution était favorable au début mais s'est compliquée après 2 mois d'une aggravation de la dysphagie et de la sténose oesophagienne. Notre observation est très particulière par la survenue d'une Pemphigoide cicatricielle chez un sujet de sexe masculin ayant un tableau grave en rapport avec l'extension des lésions à toutes les muqueuses conjonctivale, buccale, nasale, œsophagienne et même bronchique associée à une immunofluorescence directe faite d'un dépôt d'IgA uniquement. PMID:28533859

Describing the gingival involvement in a sample of 182 Italian predominantly oral mucous membrane pemphigoid patients: A retrospective series

PubMed Central

Arduino, Paolo G.; Broccoletti, Roberto; Carbone, Mario; Conrotto, Davide; Pettigiani, Erica; Giacometti, Silvia; Gambino, Alessio; Elia, Alessandra; Carrozzo, Marco

2017-01-01

Background The oral cavity has been frequently described as the only site of involvement or as the first manifestation of mucous membrane pemphigoid (MMP), being the gingival tissues often involved, but usually this has been effusively detailed in limited case series. This is a retrospective evaluation of the gingival involvement in 182 Italian patients with oral MMP. Material and Methods The diagnosis of MMP was established by both clinical morphology and direct immunofluorescence finding. Patient information (age, gender, risk factors and medical status) and parameters of manifestation (lesions’ distribution, site and type) were detailed. Results The mean age was 62 years for women (n=137) and 67 years for men (n=45). Patients had several sites of oral involvement; the gingiva was the most common one, affecting 151 patients (82.96%; 119 f - 32 m). Female subjects had more possibilities to develop gingival lesions than male patients (P = 0.005). Sixty-five patients (35.7%; 58 f - 7 m) had pure gingival involvement. Patients with lower gingival involvement statistically had more complaints (P = 0.006). Conclusions This report is one of the largest about predominantly oral MMP cases, detailing the very frequent gingival involvement; this could be crucial not only for oral medicine specialists but also for primary dental healthcare personnel and for periodontists. Key words:Mucous membrane pemphigoid, gingival status, clinical features. PMID:28160581

Use of Cross-linked Donor Corneas as Carriers for the Boston Keratoprosthesis

ClinicalTrials.gov

2017-09-14

Chemical Injuries; Unspecified Complication of Corneal Transplant; Autoimmune Diseases; Ocular Cicatricial Pemphigoid; Stevens Johnson Syndrome; Lupus Erythematosus, Systemic; Rheumatoid Arthritis; Other Autoimmune Diseases

Oral Rehabilitation of a Severe Periodontally Involved Patient with Mucous Membrane Pemphigoid: A 15-Year Follow-Up Case Report.

PubMed

Megarbane, Jean-Marie; Freiha, Cécile; Mokbel, Nadim

Mucous membrane pemphigoid (MMP) refers to a group of chronic autoimmune subepithelial diseases distinguished by erosive lesions of the mucous membranes and skin. Its treatment consists of inhibition of the inflammatory reaction by means of corticosteroids and symptomatic medication. This is a report of a patient suffering from a combination of MMP and severe generalized chronic periodontitis. The patient has been treated with oral corticosteroids, initial phase therapy, extraction with immediate implant placement, and periodontal surgery where the prognosis was questionable. The case has been followed up for 15 years. Periodontal therapy with immediate implant placement was determined to be a viable modality to achieve a total rehabilitation of a case suffering from MMP combined with severe generalized chronic periodontitis.

Bullous pyoderma gangrenosum complicated by disseminated intravascular coagulation with subsequent myelodysplastic syndrome (chronic myelomonocytic leukemia).

PubMed

Rogalski, Christina; Paasch, Uwe; Glander, Hans-Jürgen; Haustein, Uwe-Frithjof

2003-01-01

A 33-year-old woman developed a bullous PG precursing a chronic myelomonocytic leukemia (CMML) complicated by life-threatening, disseminated, intravascular coagulation after administration of systemic corticosteroids in combination with immunosuppressant and antibiotic agents. Although the association between PG and leukemia, as well as the coincidence of disseminated intravascular coagulation (DIC) and leukemia, is well known, a premonitoring effect of PG in combination with DIC preceding the diagnosis of chronic myelomonocytic leukemia in the same patient has not been reported recently.

[Blister dermatitis caused by Epicauta flagellaria (Erichson) (Coleoptera: Meloidae) species].

PubMed

Méndez, E; Sáenz, R E; Johnson, C M

1989-09-01

This paper is the first published report of vesicular dermatitis due to blister beetles of the family Meloidae in Panamá. A familial outbreak of bullous dermatitis caused by Epicauta flagellaria (Erichson) is described. All previous cases known in the Gorgas Memorial Laboratory were associated with E. isthmica Werner. Bullous lesions are produced when cantharidin, a vesicating toxin contained in the beetle's body, is released at the time the insect is crushed or rubbed upon the exposed skin. Rules for the treatment and prevention of this disease are indicated.

Corrosive poisoning mimicking cicatricial pemphigoid: Munchausen by proxy.

PubMed

Tamay, Z; Akcay, A; Kilic, G; Peykerli, G; Devecioglu, E; Ones, U; Guler, N

2007-07-01

Munchausen by proxy (MBP) is a severe form of abuse in which a caregiver simulates or fabricates illness in another person, primarily the elderly and children, which can even result in death. We report two siblings who were victims of MBP, one of whom died. A very rare diagnosis, cicatricial pemphigoid was suspected in the 2-year-old girl who was first abused. She was hospitalized twice, for 3 and 4 months, respectively. Her second hospitalization ended with her death. MBP was diagnosed after the second sibling's admission with similar atypical signs and symptoms. It was realized that a household-cleaning product, sodium hydroxide, was administered repeatedly by oral route to the children by their own mother. Physicians must consider the diagnosis of MBP whenever they are confronted with unusual, persistent or recurrent signs and symptoms in a child.

Skin ulcers related to chronic graft-versus-host disease: clinical findings and associated morbidity.

PubMed

Jachiet, M; de Masson, A; Peffault de Latour, R; Rybojad, M; Robin, M; Bourhis, J-H; Xhaard, A; Dhedin, N; Sicre de Fontbrune, F; Suarez, F; Barete, S; Parquet, N; Nguyen, S; Ades, L; Rubio, M-T; Wittnebel, S; Bagot, M; Socié, G; Bouaziz, J-D

2014-07-01

According to the National Institutes of Health classification of chronic graft-versus-host disease (cGVHD), skin ulcers after allogeneic haematopoietic stem-cell transplantation (HSCT) are recorded as having the maximal severity score but published data are scarce. To describe skin ulcers related to cGVHD with an emphasis on clinical findings, associated morbidity, management and evolution. A multicentre retrospective analysis was carried out of patients with a diagnosis of cGVHD skin ulcers. All 25 patients included in the study had sclerotic skin cGVHD and 21 had lichenoid skin lesions associated with the sclerotic skin lesions. Thirteen patients had severe cGVHD without considering the skin, because of the involvement of an extracutaneous organ by cGVHD. The median time from HSCT to the onset of ulcers was 44 months. In addition to scleroderma, initial skin lesions at the site of ulcers were bullous erosive lichen in 21 patients and bullous erosive morphoea in four patients. Fifteen patients had an inaugural oedema. Ulcers were mostly bilateral with a predilection for the lower limbs. They were frequently colonized but few infections occurred. Four patients died during a median follow-up period of 55 months. Chronic graft-versus-host disease skin ulcers occur in patients with sclerodermatous skin cGVHD, are associated with severe cGVHD, often start with bullous lichenoid lesions or bullous morphoea and seem to cause more morbidity than mortality, given the low rate of mortality observed in our series of patients. © 2014 British Association of Dermatologists.

Cannabis-induced bullous lung disease leading to pneumothorax: Case report and literature review.

PubMed

Mishra, Rashmi; Patel, Ravi; Khaja, Misbahuddin

2017-05-01

Marijuana use has been increasing in the United States among college students and young adults. Marijuana use has been associated with bullous lung disease which can lead to pneumothorax. There are other recreational drugs like methylphenidate, cocaine and heroin which have been associated with pneumothorax. We present a case of a 30-year-old man with spontaneous pneumothorax associated with marijuana use. The patient had no medical conditions and presented to the emergency room with chest pain. The physical examination revealed decreased breath sound on the right side of the chest. Bed side ultrasound of chest showed stratosphere sign, absent lung sliding; consistent with right-sided pneumothorax. The patient underwent placement of a chest tube. Computed tomography chest scans performed on day two also showed bullous lung disease in the right lung. Serial x-rays of the chest showed re-expansion of the lung. Despite the beneficial effects of Marijuana there are deleterious effects which are emphasized here. This case highlights the need for further studies to establish the relationship between marijuana use and lung diseases in the absence of nicotine use.

Thoracoscopic laser pneumoplasty in the treatment of diffuse bullous emphysema.

PubMed

Wakabayashi, A

1995-10-01

Thoracoscopic laser pneumoplasty in the treatment of diffuse bullous emphysema by means of a contact neodymium:yttrium-aluminum garnet laser was evaluated by a retrospective analysis of the first consecutive 500 procedures in 443 patients. The indication for thoracoscopic laser pneumoplasty was intractable dyspnea. Advanced age (mean age, 67 years), high oxygen dependency (70%), steroid use (46%), and markedly diminished physical capacity (2% bedridden and 27% wheelchair-bound) were noted. Thoracoscopic laser pneumoplasty was carried out under general anesthesia and one-lung ventilation. Type 3 bullae (381 procedures) were contracted by contact neodymium:yttrium-aluminum garnet laser and type 4 bullae (199 procedures) excised. The operative mortality rate was 4.8%. Subjective improvement was reported by 87% of the patients. Follow-up functional evaluation was available in 229 patients, which showed highly significant improvement. A comparison of preoperative and postoperative functional tests between type 3 and 4 bullae patients showed no significant difference, except the latter had higher decrease in airway resistance, residual volume, and total lung capacity. Thoracoscopic laser pneumoplasty is an effective treatment for both type 3 and 4 bullous emphysema with an acceptable risk.

A review of scoring systems for ocular involvement in chronic cutaneous bullous diseases.

PubMed

Lee, Brendon W H; Tan, Jeremy C K; Radjenovic, Melissa; Coroneo, Minas T; Murrell, Dedee F

2018-05-22

Epidermolysis bullosa (EB) and autoimmune blistering diseases (AIBD) describe a group of rare chronic dermatoses characterized by cutaneous fragility and blistering. Although uncommon, significant ocular surface disease (OSD) may occur in both and require ophthalmological assessment. Disease scoring systems have a critical role in providing objective and accurate assessment of disease severity. The objectives of this report were, firstly, to document the prevalence and severity of ocular involvement in EB/AIBD. Secondly, to review and evaluate existing ocular and systemic scoring systems for EB/AIBD. Finally, to identify areas where further development of ocular specific tools in EB/AIBD could be pursued. A literature search was performed in October 2017 utilising Medline, Embase, and Scopus databases. The results were restricted by date of publication, between 01.01.1950 and 31.10.2017. The reference lists of these articles were then reviewed for additional relevant publications. Articles of all languages were included if an English translation was available. Articles were excluded if they were duplicates, had no reference to ocular involvement in EB/AIBD or described ocular involvement in other diseases. Descriptions of ocular involvement in EB/AIBD were identified in 88 peer-reviewed journal articles. Findings reported include but are not limited to: cicatrising conjunctivitis, meibomian gland dysfunction, dry eye disease, trichiasis, symblepharon, fornix fibrosis, keratopathy, ectropion/entropion, ankyloblepharon, corneal ulceration, visual impairment and blindness. Although scoring systems exist for assessment of OSD in mucous membrane pemphigoid, no such tools exist for the other AIBD subtypes or for EB. Several systemic scoring systems exist in the dermatological literature that are efficacious in grading overall EB/AIBD severity, but have limited inclusion of ocular features. To the best of our knowledge, there is no recognised or validated scoring systems which comprehensively stages or grades the spectrum of ocular manifestations in EB/AIBD. There are a range of ocular complications documented in EB and AIBD. Development of a comprehensive ocular scoring system for EB/AIBD which incorporates the delineation between 'activity' and 'damage' would facilitate more objective patient assessment, improved longitudinal monitoring, comparison of intervention outcomes, and provide commonality for discussion of these patients due to the multidisciplinary nature of their care.

The role of intravenous immunoglobulin in treatment of mucous membrane pemphigoid: A review of literature

PubMed Central

Tavakolpour, Soheil

2016-01-01

Background: Mucous membrane pemphigoid (MMP) is considered an autoimmune blistering disease that predominantly affects mucous membranes. Various treatments are available for controlling the diseases, but not all of them may respond. Materials and Methods: PubMed and Google Scholar were searched for all the associated studies until 2015, using the keywords such as “cicatricial pemphigoid” or “ocular pemphigoid” or “mucous membrane pemphigoid” or “MMP” and “intravenous immunoglobulin” or “IVIg” to find all the relevant studies. The last search update was for September 2, 2015. Among the searched items, only English studies were included in the review. Results: After excluding nonrelevant studies, 13 studies with a total number of seventy patients with MMP who were under treatment with IVIg were analyzed. The 65 patients responded completely, one did not respond, two had partially responded, and the remaining two patients stopped IVIg therapy, which resulted in ocular cicatricial pemphigoid progression. Majority of the studies reported mild adverse effects while two of them did not report any unwanted side effect. The most common side effect was headache, followed by nausea. Most of the patients who had a cessation of IVIg therapy before achieving clinical remission experienced the disease progression. Conclusion: Overall, it can be concluded that IVIg therapy was very helpful in treatment of MMP patients who did not respond to conventional therapy or stopped using them for various side effects. Adverse effects associated with IVIg therapy were considerably lower than conventional therapy that can lead toward treatment with this agent in patients who suffer from severe side effects. PMID:27904583

Observational Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

ClinicalTrials.gov

2016-09-26

Other Specified Inflammatory Disorders of Skin or Subcutaneous Tissue; Pyoderma Gangrenosum; Erosive Pustular Dermatosis of the Scalp; Sweet's Syndrome; Behcet's Disease; Bowel-associated Dermatosis-arthritis Syndrome; Pustular Psoriasis; Acute Generalized Exanthematous Pustulosis; Keratoderma Blenorrhagicum; Sneddon-Wilkinson Disease; IgA Pemphigus; Amicrobial Pustulosis of the Folds; Infantile Acropustulosis; Transient Neonatal Pustulosis; Neutrophilic Eccrine Hidradenitis; Rheumatoid Neutrophilic Dermatitis; Neutrophilic Urticaria; Still's Disease; Erythema Marginatum; Unclassified Periodic Fever Syndromes / Autoinflammatory Syndromes; Dermatitis Herpetiformis; Linear IgA Bullous Dermatosis; Bullous Systemic Lupus Erythematosus; Inflammatory Epidermolysis Bullosa Aquisita; Neutrophilic Dermatosis of the Dorsal Hands (Pustular Vasculitis); Small Vessel Vasculitis Including Urticarial Vasculitis; Erythema Elevatum Diutinum; Medium Vessel Vasculitis

Photodynamic therapy for bullous retinal detachment: a single-center experience of case series with a 6-month follow-up study.

PubMed

Gao, Tingting; Qu, Jinfeng; Xiao, Jing; Hu, Jie; Zhao, Mingwei

2018-06-04

To evaluate the efficacy of half-dose photodynamic therapy (PDT) for the treatment of bullous retinal detachment. Interventional prospective case series in six eyes from six consecutive patients with bullous retinal detachment. The effected eyes were treated with indocyanine green angiography (ICGA)-guided half-dose PDT with multifocal and large laser spots. Clinical evaluations included best-corrected visual acuity (BCVA), ophthalmoscopy, ophthalmic B scan, fundus fluorescein angiography (FFA), optical coherence tomography (OCT), and ICGA at each scheduled visit at baseline; at 1, 3, and 6 months after PDT; and during follow-up after 6 months. All six eyes received half-dose verteporfin PDT with a mean number of therapeutic spots 2.83 ± 1.47 and a mean spot size of 4647 ± 996 μm in diameter. Three months after PDT, retinal reattachment was observed on B scans and resolution of sub-retinal fluid (SRF) was observed in OCT images for five eyes. There was no significant difference in the mean logMAR BCVA between the baseline and the value at 1 month after PDT (P = 0.477). At 3 months after PDT, the mean logMAR BCVA improved significantly from a baseline value of 1.02 to 0.54 (P = 0.044). At 6 months after PDT, the mean logMAR BCVA further improved to 0.46 (P = 0.025) and remained stable. One affected eye received a second half-dose PDT for SRF not reduced until the second month after PDT. Retinal reattachment and SRF resolution were observed at 1 and 3 months after the second therapy, respectively. BCVA improved from a baseline value of 20/63 to 20/20 at 1 month after the second PDT and remained stable until the sixth month after the second PDT. During follow-up after more than 6 months, recurrence occurred in no cases. This study demonstrated half-dose PDT with multifocal and large laser spots was an effective treatment for bullous retinal detachment contributing to the retinal reattachment, a resolution of SRF, and an improvement of BCVA. Thus, PDT for the treatment of bullous retinal detachment is considered to be a worthwhile endeavor.

Inzidenz von bullösen Autoimmunerkrankungen in Serbien: eine retrospektive Studie über 20 Jahre.

PubMed

Milinković, Mirjana; Janković, Slavenka; Medenica, Ljiljana; Nikolić, Miloš; Reljić, Vesna; Popadić, Svetlana; Janković, Janko

2016-10-01

Die meisten früheren Arbeiten zu den klinisch-epidemiologischen Merkmalen von bullösen Autoimmunerkrankungen (AIBD) konzentrierten sich vor allem auf eine einzige Krankheitsentität oder nur eine Krankheitsgruppe; nur in wenigen Studien wurde die Inzidenz verschiedener AIBD untersucht. Bei der vorliegenden Studie war es unser Ziel, das gesamte Spektrum der AIBD zu betrachten, die Inzidenz der häufigsten AIBD zu ermitteln und die zeitlichen Trends ihres Auftretens in Zentralserbien über einen Zeitraum von 20 Jahren zu untersuchen. Wir rekrutierten retrospektiv 1161 AIBD-Fälle, die in Zentralserbien von Januar 1991 bis Dezember 2010 neu diagnostiziert wurden. Die Diagnose stützte sich auf eine strikte klinische, histologische und immunhistologische Beurteilung. Folgende Inzidenzraten wurden für die einzelnen Erkrankungen ermittelt: 4,35 pro eine Million Einwohner/Jahr (pME/Jahr) für Pemphigus, 4,47 pME/Jahr für Pemphigoid, 1,42 pME/Jahr für Dermatitis herpetiformis (DH), 0,25 pME/Jahr IgA-Dermatose und 0,08 pME/Jahr für Epidermolysis bullosa acquisita. Im betrachteten Zeitraum stieg die altersbereinigte Inzidenzrate für Pemphigus und insbesondere für Pemphigoid signifikant an, während sie für DH, allerdings nicht signifikant, abnahm. Unsere Studie befasst sich zum ersten Mal mit den Inzidenzraten des gesamten Spektrums der AIBD in Serbien und untersucht die zeitlichen Trends ihres Auftretens über einen Zeitraum von 20 Jahren. Nach unserem besten Wissen wurde ein ähnlicher Befund wie der unsere, dass nämlich die Inzidenzraten von Pemphigus und Pemphigoid vergleichbar sind, bisher noch nicht publiziert. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

[Humoral immune diseases: Cutaneous vasculitis and auto-immune bullous dermatoses].

PubMed

Wechsler, Janine

2018-02-01

Humoral immunity is the cause of multiple diseases related to antibodies (IgA, IgG, IgM) produced by the patient. Two groups of diseases are identified. The first group is related to circulating antigen-antibody complexes. The antigens are various. They are often unknown. These immune complexes cause a vascular inflammation due to the complement fixation. Consequently, this group is dominated by inflammatory vasculitis. In the second group, the pathology is due to the fixation in situ of antibodies to a target antigen of the skin that is no more recognized by the patient. This group is represented by the auto-immune bullous dermatoses. Copyright © 2017. Published by Elsevier Masson SAS.

Management of long-term persistent air leakage developed after bullectomy for giant bullous lung disease associated with neurofibromatosis type 1

PubMed Central

Kim, Si-Wook

2016-01-01

Persistent air leakage is a serious and sometimes fatal complication of bullous lung disease surgery. A 32-year-old man with lung involvement of neurofibromatosis type I underwent bullectomy for huge bullae and recurrent pneumothorax. Persistent postoperative air leakage developed and the lung was totally collapsed. The initial surgery failed, but a second trial employing a novel suture technique on half-absorbed polyglycolic acid (PGA) felt successfully resolved the massive air leakage. Pneumothorax did not recur and the patient remained stable without dyspnea. Thus, a suture technique employing half-absorbed PGA felt was an effective option for managing persistent air leakage. PMID:26904244

[Kindler syndrome: three cases reports in three siblings].

PubMed

Ezzine Sebaï, N; Trojjet, S; Khaled, A; Zekri, S; Fazaa, B; Jaafoura, M-H; Kamoun, M-R

2007-10-01

Kindler syndrome is a rare type of genetic skin condition belonging to the class of bullous poikilodermia. We report three new cases of this rare syndrome. This condition was seen in two brothers aged 4 and 14 years and in their sister aged 6 years, born of a first-degree consanguineous marriage in a family with Kindler syndrome of varying degrees of severity. The three patients presented spontaneously regressive bullous eruptions, poikilodermia of gradual onset, major cutaneous atrophy on the back of the hands and the feet, pseudo-syndactyly and photosensitivity. The older brother presented a severe form complicated by chronic terminal renal failure with hydronephrosis secondary to urethral stenosis and hypertension as well as oesophageal stenosis requiring dilatation sessions. Electron microscopy examination of poikilodermic skin showed normal anchoring filaments and proliferation of the basal layer. Electron microscopy examination of rubbed poikilodermic skin from the other two siblings showed cleavage at both the superficial and deep intra-epidermal levels. Diagnosis of Kindler syndrome is based upon clinical evidence. Electron microscopic examination is used in particular to rule out congenital bullous epidermolysis. Detachment of layers at two or three different levels in relation to the dermal-epidermal junction described in the literature forms a specific but inconsistent feature of Kindler syndrome.

Bullous cryothermic dermatitis artefacta induced by deodorant spray abuse.

PubMed

Jacobi, A; Bender, A; Hertl, M; König, A

2011-08-01

Dermatitis artefacta belongs to a broad spectrum of factitious diseases of lesions usually self-induced by patients. Here we report a surprisingly effective induction of blisters and thermic dermatitis by excessive abuse of common deodorant sprays. We evaluated the clinical course and outcome in three patients with dermatitis artefacta induced by deodorant spray. A 12-year-old boy only admitted the abuse of deodorant spray after psychiatric intervention. Two adults (21-year-old and 37-year-old women) had borderline personality disorder and frankly reported the urge to induce pain by spraying for at least 100 s at a short distance. Bullous dermatitis was the acute presenting sign in all patients. The bullae were found on the extensor surfaces of the extremities, with a distribution of older lesions showing erosions and scarring and fresh lesions with intact bullae with a diameter of 3-15 cm. After searching for the causative agent and removal of the deodorant spray, clinical outcome showed a healing without and with scars. Cryo-damage by abuse of common deodorant sprays seems to become a popular mechanism by which an impressive bullous dermatitis can be artificially induced. Dermatologists and psychiatrist should be aware of this method of injury. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

The value of Tzanck smear test in diagnosis of erosive, vesicular, bullous, and pustular skin lesions.

PubMed

Durdu, Murat; Baba, Mete; Seçkin, Deniz

2008-12-01

Tzanck smear is generally used for the diagnosis of the pemphigus group of autoimmune bullous diseases and mucocutaneous herpesvirus infections. There are only a few studies in the literature investigating its diagnostic value. We aimed to investigate Tzanck smear findings and to determine the diagnostic value of this test in moist (erosive, vesicular, bullous, and pustular) skin lesions. We also aimed to develop an algorithmic approach for the diagnosis of these types of skin lesions according to the Tzanck smear findings. Samples were stained with May-Grünwald-Giemsa and evaluated by the same dermatologist. In some patients, methylene blue and Gram staining or direct immunofluorescence examinations were additionally performed. In all of the study cases, after the evaluation of clinical and laboratory findings (including, when appropriate, potassium hydroxide examination; viral serology; bacterial and fungal cultures; histopathology; direct and indirect immunofluorescence; patch testing), the definite diagnosis was established. We also determined the sensitivity and the specificity of certain Tzanck smear findings. Tzanck smear was performed in a total of 400 patients with moist skin lesions. The sensitivities of multinucleated giant cells and acantholytic cells in herpetic infections, dyskeratotic acantholytic cells and cocci in bullous impetigo, pseudohyphae in candidiasis, acantholytic cells in pemphigus and more than 10 tadpole cells (magnification x100) in spongiotic dermatitis were 84.7%, 92%, 100%, 100%, and 81.5%, respectively. Because Tzanck smears were evaluated by the same dermatologist, no comment could be made regarding the interobserver reliability of this test and how the level of experience with this technique might affect the results. Also, the sensitivity and the specificity of Tzanck smear test findings for certain diseases could not be calculated because of an insufficient number of patients. The Tzanck smear test is an inexpensive, useful, and an easy diagnostic tool for certain skin diseases.

Cicatricial Pemphigoid

MedlinePlus

... can usually prevent blindness. © 2005 American Academy of Oral and Maxillofacial Pathology 214 North Hale Street Wheaton, IL 60187 Tel.: 630-510-4552 Fax: 630-510-4501 Toll Free: 888-552-2667 Email: ... mucous membranes, that is, the moist linings of the mouth, the eyes, the nose and throat, and the ...

Bullae

MedlinePlus

Habif TP. Principles of diagnosis and anatomy. In: Habif TP, ed. Clinical Dermatology . 6th ed. Philadelphia, PA: Elsevier; 2016:chap 1. Habif TP. Vesicular and bullous diseases. In: Habif TP, ed. ...

Risk of progression in macula-on rhegmatogenous retinal detachment.

PubMed

Callizo, Josep; Pfeiffer, Sebastian; Lahme, Eva; van Oterendorp, Christian; Khattab, Mohammed; Bemme, Sebastian; Kulanga, Miroslav; Hoerauf, Hans; Feltgen, Nicolas

2017-08-01

To identify factors that may lead to a rapid progression in macula-on rhegmatogenous retinal detachment (RRD), in particular, those that may lead to macular involvement. Observational, prospective, single-center study. Patients referred for surgery due to primary rhegmatogenous retinal detachment with the macula on between 2009 and 2013 were included. Relevant factors analyzed included age, time delay until surgery, lens status, myopia, the detachment's location and configuration as well as number, size and type of retinal breaks. Eyes underwent optical coherence tomography to detect macular detachment. A multivariate analysis was performed to investigate the effect of several factors in the progression of retinal detachment. A total of 116 eyes of 116 patients were included. Mean time delay between admission and surgery was 1.8 ± 1.4 days. Progression was observed in 19.8% of the eyes. Of those, 47.8% presented macular detachment. Ten of the 11 (90.9%) eyes presenting progression involving the macula also exhibited a bullous configuration, which was the only parameter that correlated significantly with detachment progression in patients with (p = 0.0036) and without (p = 0.0014) macular involvement. For the first time in a prospective trial, a bullous configuration was found to be a highly significant predictor for progression in macula-on detachments. Our data support prompt surgery in patients diagnosed with bullous macula-on RRD.

Acquired reactive perforating collagenosis and pseudoporphyric bullous dermatosis in a hemodialysis patient.

PubMed

Sabanis, Nikos; Paschou, Eleni; Gavriilaki, Eleni; Kalaitzoglou, Asterios; Papanikolaou, Dimitrios; Vasileiou, Sotiris; Amplianitis, Ioannis

2016-07-01

Hemodialysis patients present with a broad spectrum of specific and nonspecific skin disorders, which rarely coexist. We report an exceptional case of a hemodialysis patient that developed acquired reactive perforating collagenosis and pseudoporphyric bullous dermatosis on the basis of common skin disorders which include hyperpigmentation, pruritus, xerosis cutis, and Linsday's nails. Interestingly, our patient presented with two unusual but distinctive cutaneous dermopathies on the background of other commonly seen skin alterations. The patient was successfully treated with allopurinol and N-acetylcysteine. Avoidance of potentially triggering factors such as alcohol, sunlight exposure and certain medication was recommended. Thus, increasing clinical awareness, assiduous investigation and early treatment of skin disorders are required to improve the prognosis and quality of life in this patient population. © 2016 International Society for Hemodialysis.

Identification of epitopes within integrin β4 for binding of auto-antibodies in ocular cicatricial and mucous membrane pemphigoid: preliminary report.

PubMed

Rashid, Khwaja Aftab; Foster, C Stephen; Ahmed, A Razzaque

2013-11-19

To identify the epitopes on human β4 integrin to which the sera of patients with ocular cicatricial pemphigoid (OCP) and mucous membrane pemphigoid (MMP) without ocular involvement bind. Fragments of the intracellular domain of the β4 molecule were cloned, expressed, purified and peptides were synthesized. Antibodies to various fragments and peptides were produced in rabbits. Binding specificity was determined via Western blot and blocking experiments. Test sera and controls were injected into neonatal BALB/c mice for in vivo passive transfer. Sera from patients with OCP, MMP, and both OCP and MMP were bound to cloned fragments of IC3.0. Its subcloned fragments IC3.4 (1489 aa-1572 aa) and IC3.4.1 (1489 aa-1510 aa) were bound with the sera from patients with OCP only. Subcloned fragments IC3.6 (1573 aa-1822 aa) and IC3.6.1 (1689 aa-1702 aa) were bound with MMP sera only. No cross-reactivity in binding was observed. Immuno-affinity-purified sera from patients with OCP, MMP, and rabbit antibodies to IC3.0, IC3.4, IC3.4.1, IC3.6, and IC3.6.1, when injected in neonatal BALB/c mice, produced subepidermal blisters in their skin. These preliminary observations identified IC3.4.1 as the possible epitope for the binding of OCP auto-antibody and IC3.6.1 as the possible epitope for the binding of MMP auto-antibody without ocular disease. Antibodies specific to these peptides produced blisters when injected in mice. Still-unidentified epitopes may exist. These observations may enhance our understanding of the role of β4 integrin in the pathobiology of OCP and MMP. Early diagnosis may be possible if serologic tests with specificity and sensitivity can be developed.

Nursing diagnoses in patients with immune-bullous dermatosis.

PubMed

Brandão, Euzeli da Silva; Santos, Iraci Dos; Lanzillotti, Regina Serrão; Ferreira, Adriano Menis; Gamba, Mônica Antar; Azulay-Abulafia, Luna

2016-08-15

identify nursing diagnoses in patients with immune-bullous dermatosis. a quantitative and descriptive research, carried out in three institutions located in Rio de Janeiro and Mato Grosso do Sul, Brazil, using the Client Assessment Protocol in Dermatology during a nursing consultation. Simple descriptive statistics was used for data analysis. 14 subjects participated in the study, nine with a diagnosis of pemphigus vulgaris, pemphigus two and three of bullous pemphigoid. The age ranged between 27 and 82 years, predominantly females (11). 14 nursing diagnoses were discussed and identified from a clinical rationale in all study participants, representing the most common human responses in this sample. The application of the Assessment Protocol in Dermatology facilitated the comprehensive assessment, in addition to providing the identification of diagnostics according to the North American Nursing Diagnosis Association International. the nursing diagnoses presented confirm the necessity of interdisciplinary work during the care for this clientele. For better description of the phenomena related to the client in question, it is suggested the inclusion of two risk factors related in three diagnoses of this taxonomy. It is worth noting the contribution of the findings for the care, education and research in nursing in dermatology. identificar diagnósticos de enfermagem em clientes com dermatoses imunobolhosas. pesquisa quantitativa e descritiva, realizada em três instituições localizadas no Rio de Janeiro e no Mato Grosso do Sul-Brasil, aplicando o Protocolo de Avaliação do Cliente em Dermatologia, durante consulta de enfermagem. Utilizou-se a estatística descritiva simples para análise dos dados. participaram do estudo 14 sujeitos, nove com diagnóstico médico de pênfigo vulgar, dois de foliáceo e três de penfigoide bolhoso. A idade variou entre 27 e 82 anos, predominando 11 pessoas do sexo feminino. Foram discutidos 14 diagnósticos de enfermagem identificados a partir do raciocínio clínico, em todos os participantes do estudo, representando as respostas humanas mais frequentes nesta amostra. A aplicação do Protocolo de Avaliação do Cliente em Dermatologia facilitou a avaliação integral, além de propiciar a identificação dos diagnósticos de acordo com a North American Nursing Diagnosis Association International. os diagnósticos de enfermagem apresentados ratificam a necessidade do trabalho interdisciplinar durante atendimento a esta clientela. Para melhor descrição dos fenômenos relacionados à clientela em questão, sugere-se a inclusão de dois fatores de risco/relacionados em três diagnósticos desta taxonomia. Cabe ressaltar a contribuição dos achados para o cuidar/educar/pesquisar em enfermagem em dermatologia. identificar los diagnósticos de enfermería en pacientes con inmuno dermatosis ampollosa. investigación cuantitativa y descriptiva, realizada en tres instituciones ubicadas en Río de Janeiro y Mato Grosso do Sul, Brasil, utilizando el Protocolo de Evaluación del Cliente en Dermatología en la consulta de enfermería. Se utilizó estadística descriptiva simples para el análisis de datos. 14 sujetos participaron en el estudio, nueve con diagnóstico de pénfigo vulgar, dos de pénfigo foliáceo y tres de penfigoide ampolloso. La edad osciló entre 27 y 82 años, predominio femenino con 11 mujeres. Se discutieron 14 diagnósticos de enfermería identificados desde el razonamiento clínico, en todos los participantes en el estudio, que representa las respuestas humanas más comunes en esta muestra. La aplicación del Protocolo de Evaluación de Dermatología facilitó la evaluación global, además de proporcionar la identificación de los diagnósticos de acuerdo con la North American Nursing Diagnosis Association International. los diagnósticos de enfermería presentados confirman la necesidad del trabajo interdisciplinario en el servicio a estos clientes. Para una mejor descripción de los fenómenos relacionados con los clientes en cuestión, se sugiere la inclusión de dos factores de riesgo/relacionados en tres diagnósticos de esta taxonomía. Vale la pena señalar la contribución de los hallazgos para el cuidado/educación/investigación en enfermería en dermatología.

Nikolsky sign

MedlinePlus

Garber B, Cydulka RK. Dermatologic presentations. In: Marx JA, Hockberger RS, Walls RM, et al, eds. Rosen's Emergency Medicine: Concepts and Clinical Practice . 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 120. Habif TP. Vesicular and bullous ...

Bullous Keratopathy

MedlinePlus

... Pill Identifier Commonly searched drugs Aspirin Metformin Warfarin Tramadol Lactulose Ranitidine News & Commentary Recent News Afib and Weight AHA: Using Electricity to Test Your Risk for Heart Failure Close Siblings Can Ease the Pain of Family Conflict Don't Turn Into a ...

Association of linear IgA bullous disease with ulcerative colitis: a case of successful treatment with infliximab.

PubMed

Yamada, S; Makino, T; Jinnin, M; Sakai, K; Fukushima, S; Inoue, Y; Ihn, H

2013-01-01

Linear IgA bullous disease (LABD) has been reported in association with inflammatory bowel disease, in particular ulcerative colitis (UC). We reporting a 34-year-old female who developed LABD during a flare-up of UC. We administered infliximab, which has been approved for the treatment of UC; infliximab dramatically improved the cutaneous lesions and bowel symptoms. This is the first report showing a marked effect of infliximab on LABD. First, we hypothesize that infliximab works for UC and then calms down excessive production of inflammatory cytokines and autoantibodies, and so stricter control of UC by infliximab is beneficial against the skin condition of LABD. Second, we suggest that TNF-α production in the lesion of LABD is increased, so TNF-α plays an important role in developing cutaneous lesions. This case suggests that infliximab, a monoclonal antibody against TNF-α, is efficacious in the cutaneous symptoms of LABD.

A case of bullous dermatitis artefacta possibly induced by a deodorant spray.

PubMed

Ikenaga, Satsuki; Nakano, Hajime; Umegaki, Noriko; Moritsugu, Ryuta; Aizu, Takayuki; Kuribayashi, Michihito; Hanada, Katsumi

2006-01-01

Dermatitis artefacta is one of a spectrum of factitious diseases etiologically responsible for skin lesions denied by patients. These factors often make it difficult to identify the causative agents of the condition. Herein, we report a case of bullous dermatitis artefacta in a 12-year-old girl, for which a deodorant spray was suspected as the probable cause. Pathological examination revealed subepidermal blistering with full-thickness necrosis of the epidermis, suggesting a thermo- or cryo-induced injury. Psychological testing demonstrated her immaturity and dependence. In searching for the causative agent, we suspected a deodorant spray as a blister-inducing agent. We succeeded in reproducing a similar blister lesion on the volunteer's healthy skin using the same spray. Psychiatric involvement significantly complicates the treatment of factitious diseases, including dermatitis artefacta. Cooperation among dermatologists, psychiatrists and the patient's family members is required for ensuring a favorable prognosis.

Blisters and Loss of Epidermis in Patients With Lupus Erythematosus

PubMed Central

Merklen-Djafri, Carine; Bessis, Didier; Frances, Camille; Poulalhon, Nicolas; Debarbieux, Sébastien; Cordel, Nadège; Lipsker, Dan

2015-01-01

Abstract The nosology of bullous lesions or equivalents (vesicles, erosions, and crusts) in patients with lupus erythematosus (LE) is rarely addressed. The primary aim of this study was to draw up a precise phenotypic inventory of such skin lesions; the secondary objective was to assess a potential relationship between the different types of loss of epidermis and extracutaneous lupus manifestations. We conducted a retrospective multicenter study including 22 patients with definite LE and bullous lesions or equivalents. All biopsies were reviewed. Patients were recruited in the dermatology departments of 6 centers. Patients were included if they met the diagnosis of systemic LE according to American College of Rheumatology and/or Systemic Lupus International Collaborating Clinics criteria or diagnosis of cutaneous LE based on classic clinical criteria and/or histological ascertainment of LE. Patients were recruited through clinician's memory and photographic collections. Three clinico-pathological patterns could be individualized. First, toxic epidermal necrolysis (TEN)-like, sheet-like, skin detachment; sun-exposure, mild mucosal involvement, and dermal mucin deposition allow differential diagnosis with classical Lyell syndrome. Second, vesiculo-bullae and/or crusting occurring on typical lesions of subacute cutaneous lupus erythematosus or chronic cutaneous lupus erythematosus. Third, tense vesicles and/or blisters with an underlying neutrophilic dermatosis and a usual response to dapsone. A careful analysis of 22 LE patients with epidermal detachment reveals 2 main pathomechanisms: a classic LE interface dermatitis, which can be hyperacute and lead to TEN-like skin detachment; and a neutrophilic dermatosis, with tense vesicles and/or blisters, including classic bullous LE. PMID:26579826

Reliability and validity of the Chinese version of the autoimmune bullous disease quality of life (ABQOL) questionnaire.

PubMed

Yang, Baoqi; Chen, Guo; Yang, Qing; Yan, Xiaoxiao; Zhang, Zhaoxia; Murrell, Dédée F; Zhang, Furen

2017-02-02

The autoimmune bullous diseases quality of life (ABQOL) questionnaire was recently developed by an Australian group and has been validated in Australian and North American patient cohorts. It is a 17-item, multidimensional, self-administered English questionnaire. The study aimed to validate the Chinese version of the ABQOL questionnaire and evaluate the reliability in Chinese patients. The Chinese version of the ABQOL questionnaire was produced by forward-backward translation and cross-cultural adaptation of the original English version. The ABQOL questionnaire was then distributed to a total of 101 patients with autoimmune bullous diseases (AIBDs) together with the Dermatology Life Quality Index (DLQI) and the 36-item Short Form Health Survey (SF-36). Validity was analyzed across a range of indices and reliability was assessed using internal consistency and test-retest methods. The Chinese version of the ABQOL questionnaire has a high internal consistency (Cronbach's alpha coefficient, 0.88) and test-retest reliability (the intraclass correlation coefficient, 0.87). Face and content validity were satisfactory. Convergent validity testing showed that the correlation coefficients for the ABQOL and DLQI was 0.77 and for the ABQOL and SF-36 was -0.62. In terms of discriminant validity, there was no significant difference between the proportions of insensitive items in ABQOL and DLQI (p = 0.236). There was no significant difference between the proportions of insensitive items in ABQOL and SF-36 (p = 0.823). The Chinese version of the ABQOL questionnaire has adequate validity and reliability. It may constitute a useful instrument to measure disease burden in Chinese patients with AIBDs.

Outcomes of cataract surgery in eyes with a low corneal endothelial cell density.

PubMed

Yamazoe, Katsuya; Yamaguchi, Takefumi; Hotta, Kazuki; Satake, Yoshiyuki; Konomi, Kenji; Den, Seika; Shimazaki, Jun

2011-12-01

To evaluate the surgical outcomes of cataract surgery in eyes with a low preoperative corneal endothelial cell density (ECD) and analyze factors affecting the prognosis. Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan. Noncomparative case series. Eyes with a preoperative ECD of less than 1000 cells/mm(2) that had cataract surgery between 2006 and 2010 were identified. Standard phacoemulsification with intraocular lenses was performed using the soft-shell technique. The rate of endothelial cell loss, incidence of bullous keratopathy, and risk factors were retrospectively assessed. Sixty-one eyes (53 patients) with a low preoperative ECD were identified. Preoperative diagnoses or factors regarded as causing endothelial cell loss included Fuchs dystrophy (20 eyes), laser iridotomy (16 eyes), keratoplasty (10 eyes), traumatic injury (3 eyes), trabeculectomy (3 eyes), corneal endotheliitis (2 eyes), and other (7 eyes). The corrected distance visual acuity improved from 0.59 ± 0.49 logMAR preoperatively to 0.32 ± 0.48 logMAR postoperatively (P<.001). The mean ECD was 693 ± 172 cells/mm(2) and 611 ± 203 cells/mm(2), respectively (P=.001). The mean rate of endothelial cell loss was 11.5% ± 23.4%. Greater ECD loss was associated with a shorter axial length (AL) (<23.0 mm) and diabetes mellitus. Bullous keratopathy developed in 9 eyes (14.8%) and was associated with posterior capsule rupture. The results suggest that modern techniques for cataract surgery provide excellent visual rehabilitation in many patients with a low preoperative ECD. Shorter AL, diabetes mellitus, and posterior capsule rupture were risk factors for greater ECD loss and bullous keratopathy. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Clinical and immunological studies of 49 cases of various types of intercellular IgA dermatosis and 13 cases of classical subcorneal pustular dermatosis examined at Kurume University.

PubMed

Hashimoto, T; Teye, K; Ishii, N

2017-01-01

Intercellular IgA dermatosis (IAD) is a subset of autoimmune bullous disease exclusively with IgA antikeratinocyte cell-surface antibodies. The classification and pathogenesis of this condition are still obscure. To classify IAD and study its pathogenesis. From our cohort of 5402 cases of autoimmune bullous disease, we selected 49 cases of various types of intercellular IgA dermatosis (IAD) and 13 cases of classical subcorneal pustular dermatosis (SPD), for which sera and information were available. We studied these cases clinically and immunologically. There were 17 SPD-type IAD, 12 intraepidermal neutrophilic IgA dermatosis (IEN)-type IAD, two IgA-pemphigus vegetans, four IgA-pemphigus foliaceus, six IgA-pemphigus vulgaris and eight unclassified IAD cases. There was no sex predominance, and the average age at disease onset was 45·9 years. Clinically, bullous and pustular skin lesions developed on various sites, particularly intertriginous areas. Histopathology showed intraepidermal blisters or pustules at the upper epidermis in the SPD-type and at the midepidermis in the IEN-type. Immunological studies revealed that direct immunofluorescence, indirect immunofluorescence of normal human skin and enzyme-linked immunosorbent assays (ELISAs) of recombinant proteins of desmogleins and desmocollins frequently showed positive results, although no antigens were detected in many cases. All cases of classical SPD, which showed no positive immunological results, were indistinguishable clinically and histopathologically from SPD-type IAD. The present study of the largest cohort of cases of IAD showed that the major subtypes are SPD and IEN, and that the combination of indirect immunofluorescence and ELISAs of desmogleins and desmocollins, in addition to direct immunofluorescence, was useful for the diagnosis of IAD and its subtypes. © 2016 British Association of Dermatologists.

Idiopathic linear IgA bullous dermatosis: prognostic factors based on a case series of 72 adults.

PubMed

Gottlieb, J; Ingen-Housz-Oro, S; Alexandre, M; Grootenboer-Mignot, S; Aucouturier, F; Sbidian, E; Tancrede, E; Schneider, P; Regnier, E; Picard-Dahan, C; Begon, E; Pauwels, C; Cury, K; Hüe, S; Bernardeschi, C; Ortonne, N; Caux, F; Wolkenstein, P; Chosidow, O; Prost-Squarcioni, C

2017-07-01

Linear IgA bullous dermatosis (LABD) is a clinically and immunologically heterogeneous, subepidermal, autoimmune bullous disease (AIBD), for which the long-term evolution is poorly described. To investigate the clinical and immunological characteristics, follow-up and prognostic factors of adult idiopathic LABD. This retrospective study, conducted in our AIBD referral centre, included adults, diagnosed between 1995 and 2012, with idiopathic LABD, defined as pure or predominant IgA deposits by direct immunofluorescence. Clinical, histological and immunological findings were collected from charts. Standard histology was systematically reviewed, and indirect immunofluorescence (IIF) on salt-split skin (SSS) and immunoblots (IBs) on amniotic membrane extracts using anti-IgA secondary antibodies were performed, when biopsies and sera obtained at diagnosis were available. Prognostic factors for complete remission (CR) were identified using univariate and multivariate analyses. Of the 72 patients included (median age 54 years), 60% had mucous membrane (MM) involvement. IgA IIF on SSS was positive for 21 of 35 patients tested; 15 had epidermal and dermal labellings. Immunoelectron microscopy performed on the biopsies of 31 patients labelled lamina lucida (LL) (26%), lamina densa (23%), anchoring-fibril zone (AFz) (19%) and LL+AFz (23%). Of the 34 IgA IBs, 22 were positive, mostly for LAD-1/LABD97 (44%) and full-length BP180 (33%). The median follow-up was 39 months. Overall, 24 patients (36%) achieved sustained CR, 19 (29%) relapsed and 35% had chronic disease. CR was significantly associated with age > 70 years or no MM involvement. No prognostic immunological factor was identified. Patients with LABD who are < 70 years old and have MM involvement are at risk for chronic evolution. © 2017 British Association of Dermatologists.

Military Vision Research Program. Addendum

DTIC Science & Technology

2011-08-01

keratitis, ocular cicatricial pemphigoid and dry eye syndromes. In some diseases, overproduction of mucin owing to excessive goblet cell proliferation and...cell density and mucin secretion has been observed in dry eye patients and inflammation can lead to goblet cell apoptosis; 2. A reduced goblet cell...of goblet cell mucin secretion in severe dry eye patients.3 It was therefore of interest to investigate the role of goblet cells in regulating

A chandelier-illuminated anterior chamber maintainer for use during descemet stripping automated endothelial keratoplasty in patients with advanced bullous keratopathy.

PubMed

Inoue, Tomoyuki; Oshima, Yusuke; Hori, Yuich; Maeda, Naoyuki

2010-08-01

A new 25-gauge illuminated anterior chamber maintainer composed of a 25-gauge infusion cannula through which a 29-gauge chandelier fiber probe passes was developed for use during Descemet stripping automated endothelial keratoplasty to treat patients with advanced bullous keratopathy. This device, which is compatible with a xenon or mercury vapor illuminator to generate powerful wide-angle illumination from the cone-shaped chandelier fiber tip, is self-retained at the corneal limbus after insertion of the infusion cannula through a corneal side port. Because of its bifunctionality, that is, bright illumination and adequate irrigation flow, excellent visibility with stable anterior chamber maintenance can be concurrently obtained for Descemet stripping, endothelial graft insertion, and subsequent intraocular manipulations without the need for use of a biologic staining technique or ophthalmic viscosurgical products even in patients with severe corneal haze. This new device facilitates safe and simple intraocular manipulation during Descemet stripping automated endothelial keratoplasty.

[Evaluation of Iris Morphology Viewed through Stromal Edematous Corneas by Infrared Camera].

PubMed

Kobayashi, Masaaki; Morishige, Naoyuki; Morita, Yukiko; Yamada, Naoyuki; Kobayashi, Motomi; Sonoda, Koh-Hei

2016-02-01

We reported that the application of infrared camera enables us to observe iris morphology in Peters' anomaly through edematous corneas. To observe the iris morphology in bullous keratopathy or failure grafts with an infrared camera. Eleven bullous keratopathy or failure grafts subjects (6 men and 5 women, mean age ± SD; 72.7 ± 13.0 years old) were enrolled in this study. The iris morphology was observed by applying visible light mode and near infrared light mode of infrared camera (MeibomPen). The detectability of pupil shapes, iris patterns and presence of iridectomy was evaluated. Infrared mode observation enabled us to detect the pupil shapes in 11 out of 11 cases, iris patterns in 3 out of 11 cases, and presence of iridetomy in 9 out of 11 cases although visible light mode observation could not detect any iris morphological changes. Applying infrared optics was valuable for observation of the iris morphology through stromal edematous corneas.

Plakins in development and disease.

PubMed

Sonnenberg, Arnoud; Liem, Ronald K H

2007-06-10

Plakins are large multi-domain molecules that have various functions to link cytoskeletal elements together and to connect them to junctional complexes. Plakins were first identified in epithelial cells where they were found to connect the intermediate filaments to desmosomes and hemidesmosomes [Ruhrberg, C., and Watt, F.M. (1997). The plakin family: versatile organizers of cytoskeletal architecture. Curr Opin Genet Dev 7, 392-397.]. They were subsequently found to be important for the integrity of muscle cells. Most recently, they have been found in the nervous system, where their functions appear to be more complex, including cross-linking of microtubules (MTs) and actin filaments [Leung, C.L., Zheng, M., Prater, S.M., and Liem, R.K. (2001). The BPAG1 locus: Alternative splicing produces multiple isoforms with distinct cytoskeletal linker domains, including predominant isoforms in neurons and muscles. J Cell Biol 154, 691-697., Leung, C.L., Sun, D., Zheng, M., Knowles, D.R., and Liem, R.K. (1999). Microtubule actin cross-linking factor (MACF): a hybrid of dystonin and dystrophin that can interact with the actin and microtubule cytoskeletons. J Cell Biol 147, 1275-1286.]. These plakins have also indicated their relationship to the spectrin superfamily of proteins and the plakins appear to be evolutionarily related to the spectrins, but have diverged to perform different specialized functions. In invertebrates, a single plakin is present in both Drosophila melanogaster and Caenorhabditis elegans, which resemble the more complex plakins found in mammals [Roper, K., Gregory, S.L., and Brown, N.H. (2002). The 'spectraplakins': cytoskeletal giants with characteristics of both spectrin and plakin families. J Cell Sci 115, 4215-4225.]. In contrast, there are seven plakins found in mammals and most of them have alternatively spliced forms leading to a very complex group of proteins with potential tissue specific functions [Jefferson, J.J., Leung, C.L., and Liem, R.K. (2004). Plakins: goliaths that link cell junctions and the cytoskeleton. Nat Rev Mol Cell Biol 5, 542-553.]. In this review, we will first describe the plakins, desmoplakin, plectin, envoplakin and periplakin and then describe two other mammalian plakins, Bullous pemphigoid antigen 1 (BPAG1) and microtubule actin cross-linking factor 1 (MACF1), that are expressed in multiple isoforms in different tissues. We will also describe the relationship of these two proteins to the invertebrate plakins, shortstop (shot) in Drosophila and VAB-10 in C. elegans. Finally, we will describe an unusual mammalian plakin, called epiplakin.

Lumps, Bumps, and Things that Go Itch in Your Office!

ERIC Educational Resources Information Center

McLeod, Renee P.

2004-01-01

This article presents a short case presentation and differential diagnosis of impetigo, a common, contagious, superficial skin infection that is produced by streptococci, staphylococci, or a combination of both bacteria. There are two different clinical presentations: (1) bullous impetigo; and (2) nonbullous impetigo. For years, it was thought…

Localized scleroderma: a series of 52 patients.

PubMed

Toledano, C; Rabhi, S; Kettaneh, A; Fabre, B; Fardet, L; Tiev, K P; Cabane, J

2009-05-01

Localized scleroderma also called morphea is a skin disorder of undetermined cause. The widely recognized Mayo Clinic Classification identifies 5 main morphea types: plaque, generalized, bullous, linear and deep. Whether each of these distinct types has a particular clinical course or is associated with some patient-related features is still unclear. We report here a retrospective series of patients with localized scleroderma with an attempt to identify features related to the type of lesion involved. The medical records of all patients with a diagnosis of localized scleroderma were reviewed by skilled practitioners. Lesions were classified according to the Mayo Clinic Classification. The relationship between each lesion type and various clinical features was tested by non-parametrical methods. The sample of 52 patients included 43 females and 9 males. Median age at onset was 30 y (range 1-76). Frequencies of patients according to morphea types were: plaque morphea 41 (78.8%) (including morphea en plaque 30 (57.7%) and atrophoderma of Pasini-Pierini 11 (21.1%)), linear scleroderma 14 (26.9%). Nine patients (17.3%) had both types of localized scleroderma. Median age at onset was lower in patients with linear scleroderma (8 y (range 3-44)) than in others (36 y (range 1-77)) (p=0.0003). Head involvement was more common in patients with linear scleroderma (37.5%) than in other subtypes (11.1%) (p=0.05). Atrophoderma of Pasini-Pierini was never located at the head. Systemic symptoms, antinuclear antibodies and the rheumatic factor were not associated with localized scleroderma types or subtypes. These results suggest that morphea types, in adults are not associated with distinct patient features except for age at disease onset (lower) and the localization on the head (more frequent), in patients with lesions of the linear type.

A new diagnosis of Williams-Beuren syndrome in a 49-year-old man with severe bullous emphysema.

PubMed

Wojcik, Monica H; Carmichael, Nikkola; Bieber, Frederick R; Wiener, Daniel C; Madan, Rachna; Pober, Barbara R; Raby, Benjamin A

2017-08-01

Williams-Beuren syndrome (WBS) is a chromosomal microdeletion syndrome typically presenting with intellectual disability, a unique personality, a characteristic facial appearance, and cardiovascular disease. Several clinical features of WBS are thought to be due to haploinsufficiency of elastin (ELN), as the ELN locus is included within the WBS critical region at 7q11.23. Emphysema, a disease attributed to destruction of pulmonary elastic fibers, has been reported in patients without WBS who have pathogenic variants in ELN but only once (in one patient) in WBS. Here we report a second adult WBS patient with emphysema where the diagnosis of WBS was established subsequent to the discovery of severe bullous emphysema. Haploinsufficiency of ELN likely contributed to this pulmonary manifestation of WBS. This case emphasizes the contribution of rare genetic variation in cases of severe emphysema and provides further evidence that emphysema should be considered in patients with WBS who have respiratory symptoms, as it may be under-recognized in this patient population. © 2017 Wiley Periodicals, Inc.

Concurrent Presentation of Erythrodermic Lichen Planus and Squamous Cell Carcinoma: Coincidence or Malignant Transformation?

PubMed

Ali, Neema M; Bhat, Ramesh; Rao, Shwetha B

2015-01-01

Lichen planus is a common papulosquamous disorder affecting about 1-2% of the population, neoplastic transformation of cutaneous lichen planus lesions occurs very rarely. A 40 year old female patient presented with a 1 year history of developing multiple, itchy, pigmented lesions over both lower legs which gradually spread to involve the whole body. A few tense bullae were seen on the extremities. An erythematous fleshy lesion was seen on the upper aspect of the left buttock. Skin biopsy from a plaque on the right forearm showed features suggestive of lichen planus. Skin biopsy of a bullae showed a sub epidermal bulla filled with a mixed inflammatory infiltrate. Direct immunofluorescence revealed no immunoreactants along the basement membrane zone. A diagnosis of erythrodermic lichen planus with bullous lichen planus was made. Biopsy of fleshy lesion of left buttock revealed a moderately differentiated squamous cell carcinoma. Erythrodermic lichen planus with bullous lesions and secondary squamous cell carcinoma; these occurences in a single patient is extremely rare and has not been previously reported to the best of our knowledge.

Concurrent Presentation of Erythrodermic Lichen Planus and Squamous Cell Carcinoma: Coincidence or Malignant Transformation?

PubMed Central

Ali, Neema M; Bhat, Ramesh; Rao, Shwetha B

2015-01-01

Lichen planus is a common papulosquamous disorder affecting about 1-2% of the population, neoplastic transformation of cutaneous lichen planus lesions occurs very rarely. A 40 year old female patient presented with a 1 year history of developing multiple, itchy, pigmented lesions over both lower legs which gradually spread to involve the whole body. A few tense bullae were seen on the extremities. An erythematous fleshy lesion was seen on the upper aspect of the left buttock. Skin biopsy from a plaque on the right forearm showed features suggestive of lichen planus. Skin biopsy of a bullae showed a sub epidermal bulla filled with a mixed inflammatory infiltrate. Direct immunofluorescence revealed no immunoreactants along the basement membrane zone. A diagnosis of erythrodermic lichen planus with bullous lichen planus was made. Biopsy of fleshy lesion of left buttock revealed a moderately differentiated squamous cell carcinoma. Erythrodermic lichen planus with bullous lesions and secondary squamous cell carcinoma; these occurences in a single patient is extremely rare and has not been previously reported to the best of our knowledge. PMID:26538691

Eosinophils in lichen sclerosus et atrophicus.

PubMed

Keith, Phillip J; Wolz, Michael M; Peters, Margot S

2015-10-01

The classic histopathologic features of lichen sclerosus et atrophicus (LS) include lymphoplasmacytic inflammation below a zone of dermal edema and sclerosis. The presence of eosinophils in LS has received little attention, but the finding of tissue eosinophils, particularly eosinophilic spongiosis in LS, has been suggested as a marker for the coexistence of autoimmune bullous disease or allergic contact dermatitis (or both). We sought to determine whether the histopathologic presence of dermal eosinophils or eosinophilic spongiosis (or both) in biopsies from patients with LS is associated with autoimmune bullous disease, autoimmune connective tissue disease or allergic contact dermatitis. A retrospective review of the histopathology and medical records of 235 patients with LS who were evaluated from June 1992 to June 2012 was performed. Sixty-nine patients (29%) had eosinophils on histopathology. Among patients with associated diseases, a statistically significant association between the eosinophil cohort and the cohort without eosinophils was not detected. The importance of eosinophils is uncertain, but our data suggest that the finding of tissue eosinophils alone is not sufficient to prompt an extensive workup for additional diagnoses. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Follicular hybrid cyst: a combination of bullous pilomatricoma and epidermoid cyst.

PubMed

Sanusi, Tutyana; Qu, Xiaoying; Li, Yanqiu; Zhang, Jing; Wang, Ming; Zhao, Yun; Yang, Zhen; An, Xiangjie; Qian, Yue; Wang, Chunsen; Chen, Hongxiang; Chen, Siyuan; Huang, Changzheng

2013-01-01

The follicular hybrid is composed of more than two components of pilosebaceous unit. There are several studies of hybrid cyst, combination of trichilemmal and epidermoid cyst was the most frequently reported. In this paper, we reported one case of hybrid cyst composed of bullous pilomatricoma and epidermoid cyst. A 14-year-old girl was complaint of a solitary flesh-colored to erythematous nodule with flaccid appearance sized 3.2 × 1.8 cm in diameter on her right upper back for one year. The histologic findings showed there were edema and proliferation of capillaries in the superficial dermis, a cyst in the middle to deep dermis. There were laminated keratins in the cystic space. The cyst wall was composed of two different components, one was composed of epithelial cells containing of granular layer, and another consisted of basophilic cells, transient cells and shadow cells. The cyst not related with Gardner's syndrome. Hybrid cyst such as trichilemmal cyst, epidermoid and pilomatricoma cysts maybe have same clinical features or mimicking each others, but we can distinguish them from histopathology evaluation.

Follicular hybrid cyst: a combination of bullous pilomatricoma and epidermoid cyst

PubMed Central

Sanusi, Tutyana; Qu, Xiaoying; Li, Yanqiu; Zhang, Jing; Wang, Ming; Zhao, Yun; Yang, Zhen; An, Xiangjie; Qian, Yue; Wang, Chunsen; Chen, Hongxiang; Chen, Siyuan; Huang, Changzheng

2013-01-01

The follicular hybrid is composed of more than two components of pilosebaceous unit. There are several studies of hybrid cyst, combination of trichilemmal and epidermoid cyst was the most frequently reported. In this paper, we reported one case of hybrid cyst composed of bullous pilomatricoma and epidermoid cyst. A 14-year-old girl was complaint of a solitary flesh-colored to erythematous nodule with flaccid appearance sized 3.2×1.8 cm in diameter on her right upper back for one year. The histologic findings showed there were edema and proliferation of capillaries in the superficial dermis, a cyst in the middle to deep dermis. There were laminated keratins in the cystic space. The cyst wall was composed of two different components, one was composed of epithelial cells containing of granular layer, and another consisted of basophilic cells, transient cells and shadow cells. The cyst not related with Gardner’s syndrome. Hybrid cyst such as trichilemmal cyst, epidermoid and pilomatricoma cysts maybe have same clinical features or mimicking each others, but we can distinguish them from histopathology evaluation. PMID:24294394

Case report of an atypical early onset X-linked retinoschisis in monozygotic twins.

PubMed

Murro, Vittoria; Caputo, Roberto; Bacci, Giacomo Maria; Sodi, Andrea; Mucciolo, Dario Pasquale; Bargiacchi, Sara; Giglio, Sabrina Rita; Virgili, Gianni; Rizzo, Stanislao

2017-02-24

X-linked Retinoschisis (XLRS) is one of the most common macular degenerations in young males, with a worldwide prevalence ranging from 1:5000 to 1:20000. Clinical diagnosis of XLRS can be challenging due to the highly variable phenotypic presentation and limited correlation has been identified between mutation type and disease severity or progression. We report the atypical early onset of XLRS in 3-month-old monozygotic twins. Fundus examination was characterized by severe bullous retinal schisis with pre-retinal and intraretinal haemorrhages. Molecular genetic analysis of the RS1 was performed and the c.288G > A (p. Trp96Ter) mutation was detected in both patients. Early onset XLRS is associated with a more progressive form of the disease, characterized by large bullous peripheral schisis involving the posterior pole, vascular abnormalities and haemorrhages. The availability of specific technology permitted detailed imaging of the clinical picture of unusual cases of XLRS. The possible relevance of modifying genes should be taken into consideration for the future development of XLRS gene therapy.

Ultrasound biomicroscopy after palliative surgical procedures for bullous keratopathy: a descriptive comparative study.

PubMed

Paris, Fabiana dos Santos; Gonçalves, Eliana Domingues; Morales, Maira Saad Ávila; Kanecadan, Liliane Andrade Almeida; Campos, Mauro Silveira de Queiroz; Gomes, José Álvaro Pereira; Allemann, Norma; Sato, Elcio Hideo

2014-01-01

To describe quantitative and qualitative features of eyes with advanced bullous keratopathy assessed using ultrasound biomicroscopy, before and after anterior stromal puncture (ASP) or amniotic membrane transplantation (AMT) procedures to relieve chronic pain. The present descriptive comparative study included 40 eyes of 40 patients with chronic intermittent pain due to bullous keratopathy who were randomly assigned to one of the two treatments (AMT or ASP). Ultrasound biomicroscopy (Humphrey, UBM 840, 50 MHz transducer, immersion technique) was used, and a questionnaire about pain intensity was completed preoperatively and postoperatively at days 90 and 180, respectively. Exclusion criteria were age<18 years, presence of concurrent infection, ocular hypertension, and absence of pain. In a 180-day follow-up, the AMT group exhibited mean central corneal thickness (CCT), 899.4 µm preoperatively and 1122.5 µm postoperatively (p<0.001); mean epithelial thickness (ET), 156.4 µm preoperatively and 247.8 µm postoperatively (p<0.001); and mean stromal thickness (ST), 742.9 µm preoperatively and 826.3 µm postoperatively (p=0.005). The ASP group exhibited mean CCT, 756.7 µm preoperatively and 914.8 µm postoperatively (p<0.001); mean ET, 102.1 µm preoperatively and 245.2 µm postoperatively (p<0.001); and mean ST, 654.6 µm preoperatively and 681.5 µm postoperatively (p<0.999). Correlations between CCT and pain intensity in the AMT group (p=0.209 pre- and postoperatively) and the ASP group (p=0.157 preoperatively and p=0.426 at the 180-day follow-up) were not statistically significant. Epithelial and stromal edema, Descemet's membrane folds, epithelial bullae, and the presence of interface fluid were frequently observed qualitative features. CCT increased over time in both groups. The magnitude of CCT did not correlate with pain intensity in the sample studied. The presence of interface fluid was a qualitative feature specifically found in some patients who underwent AMT.

Mutation in LEMD3 (Man1) Associated with Osteopoikilosis and Late-Onset Generalized Morphea: A New Buschke-Ollendorf Syndrome Variant

PubMed Central

Korman, Benjamin; Wei, Jun; Laumann, Anne; Ferguson, Polly; Varga, John

2016-01-01

Introduction. Buschke-Ollendorf syndrome (BOS) is an uncommon syndrome characterized by osteopoikilosis and other bone abnormalities, accompanied by skin lesions, most frequently connective tissue nevi. BOS is caused by mutations in the LEMD3 gene, which encodes the inner nuclear membrane protein Man1. We describe a unique case of osteopoikilosis associated with late-onset localized scleroderma and familial LEMD3 mutations. Case Report. A 72-year-old woman presented with adult-onset diffuse morphea and bullous skin lesions. Evaluation revealed multiple hyperostotic lesions (osteopoikilosis) suggestive of BOS. DNA sequencing identified a previously undescribed nonsense mutation (Trp621X) in the LEMD3 gene encoding Man1. Two additional family members were found to have osteopoikilosis and carry the same LEMD3 mutation. Conclusions and Relevance. We report a unique familial LEMD3 mutation in an individual with osteopoikilosis and late-onset morphea. We propose that this constellation represents a novel syndromic variant of BOS. PMID:27382493

The 2016 Bowman Lecture Conjunctival curses: scarring conjunctivitis 30 years on

PubMed Central

Dart, J K

2017-01-01

This review is in two sections. The first section summarises 35 conditions, both common and infrequent, causing cicatrising conjunctivitis. Guidelines for making a diagnosis are given together with the use of diagnostic tests, including direct and indirect immunofluorescence, and their interpretation. The second section evaluates our knowledge of ocular mucous membrane pemphigoid, which is the commonest cause of cicatrizing conjunctivitis in most developed countries. The clinical characteristics, demographics, and clinical signs of the disease are described. This is followed by a review and re-evaluation of the pathogenesis of conjunctival inflammation in mucous membrane pemphigoid (MMP), resulting in a revised hypothesis of the autoimmune mechanisms causing inflammation in ocular MMP. The relationship between inflammation and scarring in MMP conjunctiva is described. Recent research, describing the role of aldehyde dehydrogenase (ALDH) and retinoic acid (RA) in both the initiation and perpetuation of profibrotic activity in MMP conjunctival fibroblasts is summarised and the potential for antifibrotic therapy, using ALDH inhibition, is discussed. The importance of the management of the ocular surface in MMP is briefly summarised. This is followed with the rationale for the use of systemic immunomodulatory therapy, currently the standard of care for patients with active ocular MMP. The evidence for the use of these drugs is summarised and guidelines given for their use. Finally, the areas for research and innovation in the next decade are reviewed including the need for better diagnostics, markers of disease activity, and the potential for biological and topical therapies for both inflammation and scarring. PMID:28106896

The use of endoillumination probe-assisted Descemet membrane endothelial keratoplasty for bullous keratopathy secondary to argon laser iridotomy

PubMed Central

Kobayashi, Akira; Yokogawa, Hideaki; Yamazaki, Natsuko; Masaki, Toshinori; Sugiyama, Kazuhisa

2015-01-01

Purpose To report the first case of Descemet membrane endothelial keratoplasty (DMEK) for bullous keratopathy (BK) secondary to argon laser iridotomy (ALI). Patient A 71-year-old woman presented with decreased visual acuity in her right eye due to BK secondary to ALI that was performed 10 years prior. Results Phacosurgery was performed first, followed by successful DMEK 4 months later. A DMEK shooter was used for donor insertion, which allowed for a stable anterior chamber during donor insertion, even when the anterior chamber was quite shallow. Also, removal of edematous epithelial cells and endoillumination probe-assisted DMEK was quite useful to visualize DMEK graft on the background of the dark brown iris seen in Asian eyes. The patient’s best corrected visual acuity rapidly increased from 20/200 to 25/20 after 1 month, with complete resolution of corneal edema. Conclusion We reported the first successful DMEK case for BK secondary to ALI. The use of a DMEK shooter for donor insertion and endoillumination assistance to visualize the DMEK graft was a useful technique for BK secondary to ALI. PMID:25609910

Self-reported Adverse Health Events Following Smallpox Vaccination in a Large Prospective Study of US Military Service Members

DTIC Science & Technology

2007-08-27

bullous erythema multiforme (Stevens‑Johnson syndrome), eczema vaccinatum, generalized vaccinia, progressive vaccinia, and postvac‑ cinal...reported health outcomes, including mental and physical functioning , cardiovascular diseases, and auto- immune disorders, were found. These findings...words: smallpox vaccine, questionnaires, military medicine , longitudinal studies, chronic disease, quality of life [Human Vaccines 4:2, 127‑133; March

A comparison of lamellar and penetrating keratoplasty outcomes: a registry study.

PubMed

Coster, Douglas J; Lowe, Marie T; Keane, Miriam C; Williams, Keryn A

2014-05-01

To investigate changing patterns of practice of keratoplasty in Australia, graft survival, visual outcomes, the influence of experience, and the surgeon learning curve for endothelial keratoplasty. Observational, prospective cohort study. From a long-standing national corneal transplantation register, 13 920 penetrating keratoplasties, 858 deep anterior lamellar keratoplasties (DALKs), and 2287 endokeratoplasties performed between January 1996 and February 2013 were identified. Kaplan-Meier functions were used to assess graft survival and surgeon experience, the Pearson chi-square test was used to compare visual acuities, and linear regression was used to examine learning curves. Graft survival. The total number of corneal grafts performed annually is increasing steadily. More DALKs but fewer penetrating grafts are being performed for keratoconus, and more endokeratoplasties but fewer penetrating grafts are being performed for Fuchs' dystrophy and pseudophakic bullous keratopathy. In 2012, 1482 grafts were performed, compared with 955 in 2002, translating to a requirement for 264 extra corneal donors across the country in 2012. Comparing penetrating grafts and DALKs performed for keratoconus over the same era, both graft survival (P <0.001) and visual outcomes (P <0.001) were significantly better for penetrating grafts. Survival of endokeratoplasties performed for Fuchs' dystrophy or pseudophakic bullous keratopathy was poorer than survival of penetrating grafts for the same indications over the same era (P <0.001). Visual outcomes were significantly better for penetrating grafts than for endokeratoplasties performed for Fuchs' dystrophy (P <0.001), but endokeratoplasties achieved better visual outcomes than penetrating grafts for pseudophakic bullous keratopathy (P <0.001). Experienced surgeons (>100 registered keratoplasties) achieved significantly better survival of endokeratoplasties (P <0.001) than surgeons who had performed fewer grafts (<100 registered keratoplasties). In the hands of experienced, high-volume surgeons, endokeratoplasty failures occurred even after 100 grafts had been performed. More corneal transplants, especially DALKs and endokeratoplasties, are being performed in Australia than ever before. Survival of DALKs and endokeratoplasties is worse than the survival of penetrating grafts performed for the same indications over the same timeframe. Many endokeratoplasties fail early, but the evidence for a surgeon learning curve is unconvincing. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Visual acuity, refractive error, and endothelial cell density six months after Descemet stripping and automated endothelial keratoplasty (DSAEK).

PubMed

Koenig, Steven B; Covert, Douglas J; Dupps, William J; Meisler, David M

2007-07-01

To evaluate visual acuity, refractive outcomes, and endothelial cell density 6 months after Descemet stripping and automated endothelial keratoplasty (DSAEK). We performed an institutional review board-approved prospective study of a surgical case series of 34 patients at 2 institutions undergoing DSAEK for Fuchs endothelial dystrophy, pseudophakic bullous keratopathy, or aphakic bullous keratopathy with or without simultaneous phacoemulsification and intraocular lens implantation. Clinical outcomes, including best spectacle-corrected visual acuity (BSCVA), spherical equivalent refraction, and refractive astigmatism and topographic or keratometric astigmatism, were assessed at the 6-month postoperative examination and compared with preoperative values with paired Student t tests. The change in endothelial cell density from the eye bank examination to 6 months after transplantation was similarly evaluated. BSCVA averaged 20/99 preoperatively and 20/42 postoperatively (P < 0.0001). After DSAEK, 30 (88.2%) of 34 patients showed improved BSCVA, and 21 (61.8%) of the 34 patients achieved a BSCVA of 20/40 or better. For patients not undergoing simultaneous phacoemulsification and intraocular lens implantation, a hyperopic shift in refraction of 1.19 +/- 1.32 D was noted. Refractive astigmatism, topographic astigmatism, and keratometry showed no statistically significant change. Endothelial cell density of donor corneas averaged 2826 +/- 370 cells/mm, whereas the mean postoperative density was 1396 +/- 440 cells/mm. This finding corresponded to an average loss of 1426 cells/mm (50% loss; P = 0.0001). The first half of cases experienced an average cell loss of 1674 cells/mm (59% loss) compared with 1181 (41% loss) in the second half of cases (P = 0.005). Three (9%) of 34 grafts experienced iatrogenic graft failure and required reoperation with new donor tissue. Also, 9 (27%) of 34 grafts experienced dislocation in the early postoperative period and required repositioning. In this prospective study of DSAEK for bullous keratopathy and Fuchs endothelial corneal dystrophy, improvement of visual acuity was achieved with only a mild tendency toward hyperopic shift and without significant induced astigmatism. Endothelial cell loss was significant, however, and may be related to surgical experience.

Indications for and outcomes of repeat penetrating keratoplasty, 1989-1995.

PubMed

Patel, N P; Kim, T; Rapuano, C J; Cohen, E J; Laibson, P R

2000-04-01

To evaluate the indications for and outcomes of repeat penetrating keratoplasty over a 7-year period and compare them to a similar study over the prior 6-year period at the same institution. Retrospective noncomparative case series. Two hundred twenty-three consecutive repeat corneal transplants performed by one of five corneal surgeons between 1989 and 1995 were studied. Reasons for primary and regraft failure, indications for the initial corneal graft, graft clarity, and best-corrected visual acuity were measured on each patient. Between 1989 and 1995, 16% (271 of 1689) of transplants performed by our cornea group were regrafts compared with 9% (165 of 1860) in the period from 1983 to 1988 (P < 0.01). The most common indications for penetrating keratoplasty before regraft were pseudophakic bullous keratopathy (27%, 61 of 223), failed graft (20%, 44 of 223), Fuchs' dystrophy (11%, 24 of 223), aphakic bullous keratopathy (9%, 21 of 223), keratoconus (8%, 17 of 223), and herpes simplex keratitis (6%, 14 of 223). Compared with the prior study period of 1983 to 1988, an increase was revealed in the incidence of failed graft (11% to 20%, P = 0.03), and a decrease was revealed in the incidence of aphakic bullous keratopathy (19% to 9%, P = 0.01). Of the 223 regrafts, 55 (25%) failed during the study period (range, 1 month to 7.5 years; mean 2.1 years). Eleven percent (6 of 55) of regraft failures occurred within 6 months, and 55% (30 of 55) failed within 18 months. Of the 150 regrafts with 2 years follow-up (mean, 3.9 years), 111 (74%) had clear grafts. A best-corrected visual acuity of 20/20 to 20/40 was achieved in 41% (46 of 111), 20/50 to 20/100 in 32% (36 of 111), 20/200 to 20/400 in 21% (23 of 111), and counting fingers to no light perception in 5% (6 of 111). Failed grafts are increasing as an indication for penetrating keratoplasty. Graft clarity and visual acuity results continue to be very good, supporting the use of repeat corneal transplantation.

Regulation of ocular surface inflammation by prostaglandin E receptor subtype EP3.

PubMed

Ueta, Mayumi

2010-11-01

We first investigated whether the prostaglandin (PG) E2-PGE receptor subtype EP3 axis regulates the development of murine experimental allergic conjunctivitis because it has been reported that this pathway negatively regulates allergic reactions in a murine allergic asthma model. We observed that EP3 is constitutively expressed in mice conjunctival epithelium. EP3 knockout mice demonstrated significantly increased eosinophil infiltration in conjunctiva after ragweed challenge compared with wild-type mice. Consistently, significantly higher expression of eotaxin-1 messenger RNA was observed in Ptger3-/- mice. Conversely, treatment of wild-type mice with an EP3-selective agonist significantly decreased eosinophil infiltration, which was blunted in Ptger3-/- mice. Expression of cyclooxygenase-2 and PGE synthases was upregulated and PGE2 content increased in the eyelids after ragweed challenge. These data suggest that PGE2 acts on EP3 in the conjunctival epithelium and downregulates the progression of experimental allergic conjunctivitis. We next examined and compared the expression of EP3 in human conjunctival epithelium in various ocular surface diseases. Human conjunctival epithelium expressed EP3-specific messenger RNA and EP3 protein. Although we could clearly find positive signals in the conjunctival epithelium from patients with noninflammatory ocular surface diseases such as conjunctivochalasis and pterygium, we could not find positive signals in that from those with inflammatory disorders such as Stevens-Johnson syndrome and ocular cicatricial pemphigoid. Likewise, expression of the PGE receptor subtype EP4 was clearly found in the conjunctival epithelium from patients with conjunctivochalasis and pterygium but not from patients with Stevens-Johnson syndrome and ocular cicatricial pemphigoid.

[Cheilitis: Diagnosis and treatment].

PubMed

Samimi, Mahtab

2016-02-01

The whole examination of oral cavity, other mucosae and skin is required when managing a cheilitis. Irritants (climatic, mechanical, caustic agents...) constitute the main aetiological factors of cheilitis. Allergic contact cheilitis should be investigated with a detailed anamnesis in order to search any causative agent in contact with the oral mucosae. Patch testing is required to confirm the diagnosis of delayed hypersensivity. Chronic actinic cheilitis occurs mostly in middle-aged, fair-skinned men. It is a potentially malignant condition that requires biopsies to exclude severe dysplasia or carcinoma. Angular cheilitis can occur spontaneously but is frequently related with several precipitating factors, such as systemic immune suppression, local irritation and moisture, fungal and/or bacterial infection. Cheilitis can also be seen in various systemic conditions such as lichen planus, lupus, atopic dermatitis and nutritional deficiencies. Erosive and crusty cheilitis and bullous erosive stomatitis are the main oral features of erythema multiforme and Stevens-Johnson syndrome. Granulomatous macrocheilitis (cheilitis granulomatosa) presents with intermittent or permanent lip swelling. It should be confirmed by a biopsy. It can be either isolated (Miescher macrocheilitis) or associated with various systemic conditions. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Toxic epidermal necrolysis.

PubMed

Castelain, Florence; Humbert, Philippe

2012-11-01

Toxic epidermal necrolysis (TEN) is a severe mucocutaneous drug-induced syndrome that causes massive keratinocyte apoptosis and therefore hydro-electrolytic disorders and systemic infection. TEN approximately affects one to two cases per million per year. Mortality rate may reach thirty percent of cases. Thus, TEN constitutes a therapeutic emergency at diagnosis. Typically, clinical examination shows a mucocutaneous detachment involving more than thirty percent of body area. Definitive diagnosis is made on cutaneous biopsy with histological exam that shows the blister of necrotic keratinocytes. Main differential diagnosis are acute staphylococcus epidermis, acute generalized exanthematous pustulosis, linear IgA bullous dermatosis, paraneoplastic pemphigus, bullous fixed pigmented erythema, acute lupus erythematosus. In the early days, SCORTEN gives a good estimation and is now widely used as prognostic score. Drugs are generally considered as the main etiology of TEN but in some cases bacterial or viral infections could be involved. Physiopathology remains unclear even if recent advances have reported the possible implication of immune pathways based on activation of T and NK cells. Treatment of TEN requires to be instituted as soon as the diagnosis is made and the patient is preferentially referred to a specialized unit. Supportive care consist of covering areas of cutaneous detachment. No other therapy has demonstrated its efficiency, but high-dose intravenous immunoglobulin might improve the prognosis.

[Thoracic endometriosis complicated with pneumopericard and iterative pneumothorax due to bullous dystrophy].

PubMed

Kienlen, A; Fernandez, C; Henni-Laleg, Z; Andre, M; Gazaille, V; Coolen-Allou, N

2018-04-01

Thoracic endometriosis is a rare entity characterized by presence of endometrial tissue in pleura, lung parenchyma or airways. Most frequent manifestations are catamenial pneumothorax, hemothorax, hemoptysis and pulmonary nodules. We report here a rare case of a woman with thoracic endometriosis who developed iterative pneumothorax and pneumopericardium on bilateral bullous pulmonary dystrophy. She was a 37-year-old woman without any tobacco exposure and with previous history of pleural tuberculosis treated 5 years earlier. She was first referred to our centre for right pleuro-pneumothorax and hemorrhagic ascites. Pleural fluid examinations did not show any tuberculosis relapse, the evolution was favorable after thoracic drainage and there was no parenchymal lung abnormality on CT scan after surgery. Celioscopic peritoneal examination revealed stage IV peritoneal endometriosis. One year later, she was admitted for left catamenial pneumothorax. Thoracic CT scan showed apparition of large subpleural bulla. She underwent thoracotomy for bulla resection and left partial pleurectomy. Two years later, she was hospitalized for right pneumothorax and compressive pneumopericardium. Surgical lung biopsies confirmed pleuropulmonary endometriosis. Thoracotomy was performed for talcage pleurodesis and diaphragmatic leakages sutures. Lung bulla are rare in thoracic endometriosis, mechanism of their formation remains unknown. Pericardial involvement is rare in endometriosis; we report here a unique case of pneumopericardium. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Loss of Work Productivity and Quality of Life in Patients With Autoimmune Bullous Dermatoses.

PubMed

Heelan, K; Hitzig, S L; Knowles, S; Drucker, A M; Mittmann, N; Walsh, S; Shear, N H

2015-01-01

Little is known about quality of life and work productivity in autoimmune bullous dermatoses (AIBDs). To determine the impact of AIBDs on quality of life and work productivity. An observational cross-sectional study took place between February and May 2013 at an AIBD tertiary referral centre. Ninety-four patients were included. All participants completed the Dermatology Life Quality Index and the Work Productivity and Activity Impairment-Specific Health Problem questionnaires. Responders to treatment had less impairment (P<.001) than nonresponders. Patients with severe AIBD had significantly more impairment that those with mild (P<.001) and moderate (P=.002) AIBD. Greater impairment was associated with higher percentage of work missed. Those with a higher Dermatology Life Quality Index score had greater work impairment and overall activity impairment (P=.041, P=.024). Nonresponders had increased impairment while working (P<.001), overall work impairment (P<.001), and activity impairment (P<.001). Severely affected patients had worse impairment in all Work Productivity and Activity Impairment Questionnaire domains. AIBD has the potential to be a large burden on ability to work and quality of life. Larger studies are needed to clarify how these domains change over time and whether or not they improve with treatment. © The Author(s) 2015.

Management of patients with ocular manifestations in vesiculobullous disorders affecting the mouth.

PubMed

Hansen, M S; Klefter, O N; Julian, H O; Lynge Pedersen, A M; Heegaard, S

2017-10-01

Pemphigoid and pemphigus diseases as well as Stevens-Johnson syndrome present as vesiculobullous disorders of the skin and may additionally involve both the oral cavity and the ocular surface. Ocular involvement ranges from mild irritation and dry eye disease to chronic conjunctivitis, symblepharon, eyelid malposition, ocular surface scarring and severe visual loss. In addition to diagnostic assessments, ophthalmologists must treat the dry eye and meibomian gland dysfunction components of these diseases using a stepladder approach, including eyelid hygiene and lubricants. Topical anti-inflammatory therapy is used to treat acute inflammatory exacerbations of the ocular surface, but it cannot prevent scarring alone. Intralesional antimetabolite therapy can cause regression of conjunctival pathology in selected cases. Hence, patients with vesiculobullous disorders should be managed by a multidisciplinary team representing ophthalmology, dermatology, otolaryngology, oral medicine and pathology, internal medicine and intensive care. Systemic treatments including corticosteroids, azathioprine, cyclophosphamide, cyclosporine and mycophenolate mofetil help control inflammation. Intravenous immunoglobulins, plasmapheresis and targeted antibody therapy can be used in selected, severe and treatment-resistant cases. Local surgical management may include debridement of pseudomembranes, lysis of symblepharon, amniotic and mucous membrane grafting as well as reconstructive procedures. Prospective, multicentre, international studies are recommended to further support evidence-based practice. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[What's new in clinical dermatology?].

PubMed

Janier, M

2013-11-01

2013 has been the year of large genetic studies of the GWAS type (Genome wide association studies) in common diseases such as psoriasis and atopic dermatitis, aimed at localization of candidate genes. It was also the year of population-based studies from huge public or private registers. Thus, epidemiologic correlations have been put forward: psoriasis and vascular risk, psoriasis and rhinosinusitis, rosacea and migraine, acne and food habits, eczema and basal-cell carcinoma, vitiligo and lower risk of skin cancer, cutaneous Ro/SS-A pos lupus and cancer, chronic eczema and calcium-channel inhlbitors, pemphigoid and loop diuretics. Risk of IBD induced by isotretinoin has not been confirmed but risk of skin cancer under azathioprine is real. New drug reactions have appeared (pigmentation due to interferon, hypodermitis and sarcoidosis to anti-BRAF, vandetanib) and old ones are revisited (patch-testing of Severe Cutaneous adverse cutaneous reactions, pigmentation due to anti-malarial drugs, neutrophilic dermatosis due to azathioprine). Diane35(®) has been transiently withdrawn in January 2013 but tetrazepam has been withdrawn definitively in July 2013. Original aspects of cutaneous infections will be discussed along with new data on STDs (meningococcemia in MSMs, HPV, Herpes, congenital syphilis). Finally, some important papers about dermoscopy, confocal microscopy and aesthetic dermatology will be presented. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Biotherapies in inflammatory ocular disorders: Interferons, immunoglobulins, monoclonal antibodies.

PubMed

Saadoun, D; Bodaghi, B; Bienvenu, B; Wechsler, B; Sene, D; Trad, S; Abad, S; Cacoub, P; Kodjikian, L; Sève, P

2013-05-01

Biotherapies used in clinical practice for the treatment of ophthalmologic manifestations of systemic diseases include interferons (IFN), intravenous immunoglobulins (IVIG) and monoclonal antibodies (anti-TNF, anakinra, tocilizumab and rituximab). Several open prospective studies have shown the effectiveness of IFN-α (78 to 98% complete remission) for the treatment of severe uveitis in Behcet's disease. IFN is capable of inducing prolonged remission and continued after his arrest, in 20-40% of patients. Side effects (flu-like, psychological effects) limit its use in practice. Anti-TNFα (infliximab and adalimumab) represents an attractive alternative therapeutic in severe uveitis refractory to immunosuppressants, especially in Behcet's disease. They are almost always (>90% of cases) and rapidly effective but their action is often suspensive. Anti-TNFα requires an extended prescription or takes over from another immunosuppressant once ocular inflammation has been controlled. IVIG are used for the treatment of Kawasaki disease and Birdshot disease. Several open or retrospective studies showed their effectiveness for the treatment of severe and refractory cicatricial pemphigoid. Tolerance of IVIG is good but their efficacy is transient. Rituximab showed an efficacy in few observations of various inflammatory eye diseases (uveitis, scleritis and idiopathic inflammatory pseudo-tumors or associated with granulomatosis with polyangiitis) and cicatricial pemphigoid. The risk of infection associated with this biotherapy limits its use in refractory diseases to conventional therapy. Anakinra (a soluble antagonist of IL-1R) showed interesting results in terms of efficiency in one small open study in Behcet's disease. Its safety profile is good and with a quick action that could be interesting for the treatment of severe uveitis. Copyright © 2013 Elsevier B.V. All rights reserved.

A gene network bioinformatics analysis for pemphigoid autoimmune blistering diseases.

PubMed

Barone, Antonio; Toti, Paolo; Giuca, Maria Rita; Derchi, Giacomo; Covani, Ugo

2015-07-01

In this theoretical study, a text mining search and clustering analysis of data related to genes potentially involved in human pemphigoid autoimmune blistering diseases (PAIBD) was performed using web tools to create a gene/protein interaction network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was employed to identify a final set of PAIBD-involved genes and to calculate the overall significant interactions among genes: for each gene, the weighted number of links, or WNL, was registered and a clustering procedure was performed using the WNL analysis. Genes were ranked in class (leader, B, C, D and so on, up to orphans). An ontological analysis was performed for the set of 'leader' genes. Using the above-mentioned data network, 115 genes represented the final set; leader genes numbered 7 (intercellular adhesion molecule 1 (ICAM-1), interferon gamma (IFNG), interleukin (IL)-2, IL-4, IL-6, IL-8 and tumour necrosis factor (TNF)), class B genes were 13, whereas the orphans were 24. The ontological analysis attested that the molecular action was focused on extracellular space and cell surface, whereas the activation and regulation of the immunity system was widely involved. Despite the limited knowledge of the present pathologic phenomenon, attested by the presence of 24 genes revealing no protein-protein direct or indirect interactions, the network showed significant pathways gathered in several subgroups: cellular components, molecular functions, biological processes and the pathologic phenomenon obtained from the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database. The molecular basis for PAIBD was summarised and expanded, which will perhaps give researchers promising directions for the identification of new therapeutic targets.

Common pediatric and adolescent skin conditions.

PubMed

Sanfilippo, Angela M; Barrio, Victoria; Kulp-Shorten, Carol; Callen, Jeffrey P

2003-10-01

Skin lesions are encountered in all areas of medicine, and it is therefore important for physicians to understand the fundamentals of explaining and diagnosing common skin conditions. This article begins with a discussion of description and documentation of skin lesions based on color, size, morphology, and distribution. Pigmentation disorders such as vitiligo are depicted. Cutaneous growths that are found in the pediatric and adolescent population include acrochordons, dermatofibromas, keloids, milia, neurofibromas, and pyogenic granulomas. Treatment of these growths usually involves observation or curettage with electrodessication.Psoriasis, atopic dermatitis, poison ivy, and eczema are comprised of scaling patches and plaques; poison ivy and atopic dermatitis may also present with bullous and vesicular changes. Therapy typically consists of topical emollients and corticosteroids; phototherapy is reserved for refractory cases. Acne vulgaris is the most common skin disease of the pediatric and adolescent population. This condition can be psychologically debilitating and, therefore, proper treatment is of paramount importance. Therapeutic options include topical as well as oral antibiotics and retinoids. Extreme caution must be used when prescribing retinoids to post-pubescent females, as these agents are teratogenic. Vascular anomalies are most commonly exemplified as port wine stains and hemangiomas. Port wine stains may be treated with pulsed dye laser or may be observed if they are not of concern to the patient or physician. Hemangiomas typically spontaneously regress by age ten; however, there has been recent concern that certain cases may need to be treated. Dermal rashes may be localized or generalized. Treatment of generalized drug eruptions involves elimination of the inciting agent, topical antipruritics, and systemic corticosteroids for severe reactions. Infectious etiologic agents of skin disease include bacteria, fungi, and viruses. Many sexually transmitted diseases are bacterial or viral in origin and present as a rash or ulcer. Impetigo is a bacterial infection which may present as a bullous eruption or as an erosion with a honey colored crust. Other bacterial infections include erythema chronicum migrans, folliculitis, and cellulitis. Fungal infections include the various forms of tinea and are usually treated with topical antifungals; if the infection is located in a hair-bearing area, systemic antifungals are necessary. Viral infections include warts, varicella, molluscum contagiosum, and herpes. Treatment varies from observation or antivirals for varicella to cryosurgery and topical imiquimod for warts. Finally, scabies and lice are infectious agents that can be treated with permethrin and pyrethrin solutions.

Association Between Inflammatory Skin Disease and Cardiovascular and Cerebrovascular Co-Morbidities in US Adults: Analysis of Nationwide Inpatient Sample Data.

PubMed

Kwa, Michael C; Silverberg, Jonathan I

2017-12-01

Psoriasis, atopic dermatitis or eczema (AD-E), pemphigus, bullous pemphigoid (BP), and hidradenitis are chronic inflammatory skin disorders associated with systemic immune activation, considerable symptom burden, stigma, functional disturbances, and mental health symptoms. All of these might increase cardiovascular risk. The objective of this study was to determine whether these inflammatory skin diseases are associated with increased cardiovascular/cerebrovascular risk and/or disease. We analyzed data from the 2002-2012 National Inpatient Sample, including a representative 20% sample of all US hospitalizations (n = 72,108,077 adults). In multivariate logistic regression models with propensity score matching, patients hospitalized with versus without a diagnosis the inflammatory skin diseases examined had higher odds of obesity (odds ratio [95% confidence interval] for pemphigus: 1.16 [1.05-1.29]; BP 1.14 [1.06-1.23]; AD-E: 1.82 [1.79-1.86]; psoriasis: 2.36 [2.32-2.41]; hidradenitis: 2.79 [2.59-3.01]). Inflammatory skin disease was also associated with significantly higher odds of different cardiovascular risk factors, including hypertension (pemphigus: 1.39 [1.31-1.48]; BP 1.96 [1.88-2.05]; AD-E: 1.19 [1.17-1.21]; psoriasis: 1.61 [1.59-1.64]), and diabetes mellitus with complications (pemphigus: 1.34 [1.18-1.52]; BP: 2.06 [1.90-2.24]; AD-E: 1.13 [1.10-1.17]; psoriasis: 1.39 [1.35-1.44]), as well as vascular, cardiovascular, and cerebrovascular disease, including peripheral vascular disease (pemphigus: 1.14 [1.00-1.30]; BP: 1.83 [1.69-1.98]; AD-E: 1.18 [1.14-1.22]; psoriasis: 1.32 [1.28-1.35]), peripheral and visceral atherosclerosis (BP: 1.67 [1.53-1.81]; AD-E: 1.16 [1.12-1.20]; psoriasis: 1.27 [1.24-1.30]), pulmonary circulation disorders (pemphigus: 1.67 [1.39-2.01]; BP: 2.17 [1.92-2.45]; AD-E: 1.39 [1.33-1.45]; psoriasis: 1.37 [1.31-1.43]), congestive heart failure (pemphigus: 1.75 [1.60-1.90]; BP: 2.82 [2.68-2.98]; AD-E: 1.10 [1.07-1.13]; psoriasis: 1.05 [1.02-1.07]), history of transient ischemic attack (pemphigus: 1.36 [1.14-1.62]; BP: 2.03 [1.83-2.26]; AD-E: 1.19 [1.15-1.23]; psoriasis: 1.31 [1.26-1.36]), and cerebrovascular disease. In stratified analyses, multiple inflammatory skin diseases were associated with significantly higher rates of obesity, hypertension, and/or diabetes in patients aged <50 years and females. Psoriasis, pemphigus, BP, AD-E, and hidradenitis were all associated with increased cardiovascular and cerebrovascular risk, especially at younger age.

Identification of the cutaneous basement membrane zone antigen and isolation of antibody in linear immunoglobulin A bullous dermatosis.

PubMed Central

Zone, J J; Taylor, T B; Kadunce, D P; Meyer, L J

1990-01-01

Linear IgA bullous dermatosis (LABD) is a rare blistering skin disease characterized by basement membrane zone deposition of IgA. This study identifies a tissue antigen detected by patient serum and then isolates the autoantibody using epidermis and protein bands blotted on nitrocellulose as immunoabsorbents. Sera from 10 patients (9 with cutaneous disease and 1 with cicatrizing conjunctivitis) were evaluated. Indirect immunofluorescence revealed an IgA anti-basement membrane antibody in 6 of 10 sera with monkey esophagus substrate and 9 of 10 sera with human epidermal substrate. Immunoblotting was performed on epidermal and dermal extracts prepared from skin separated at the basement membrane zone with either sodium chloride or EDTA. Saline-separated skin expressed a 97-kD band in dermal extract alone that was recognized by 4 of 10 sera. EDTA-separated skin expressed the 97-kD band in both epidermal (4 of 10 sera) and dermal (6 of 10 sera) extract. Immunoabsorption of positive sera with epidermis purified an IgA antibody that reacted uniquely with the 97-kD band. In addition, IgA antibody bound to nitrocellulose was eluted from the 97-kD band and found to uniquely bind basement membrane zone. It is likely that the 97-kD protein identified by these techniques is responsible for basement membrane binding of IgA in LABD. Images PMID:2107211

Detection of Anti-basement Membrane Zone Antibodies in the Blister Fluid in Subepidermal Autoimmune Bullous Diseases

PubMed Central

Surya, Ravindran; Tejasvi, Bobbili; Shenoi, Shrutakirthi D; Pai, Sathish; Rao, Chythra; Rao, Raghavendra

2017-01-01

Background: Subepidermal autoimmune bullous diseases (sAIBD) are diverse of conditions with clinicopathological overlap. Circulating autoantibodies in the serum can be demonstrated using indirect immunofluorescence (IIF) microscopy. Artificially split normal human skin is considered as an optimum substrate for the demonstration of anti-basement membrane zone (BMZ) antibodies using IIF in sAIBD; it not only helps to detect the presence of circulating antibodies in the serum but also helps to subclassify these conditions into “roof” and “floor” binding disorders. Aim: In this study, we evaluated the utility of IIF to detect anti-BMZ antibodies in the blister fluid of patients with sAIBD. Materials and Methods: Twenty-two patients with a clinical diagnosis of sAIBD were enrolled in the study. IIF of serum and blister fluid were done simultaneously using salt-split skin as a substrate. Results: Anti-BMZ antibodies could be detected in the blister fluid using IIF in all patients in the study group. Limitation: We could not do enzyme-linked immunosorbent assay of blister fluid. This would have given us the quantitative data of circulating antibodies in the blister fluid. Conclusion: Blister fluid offers an alternate source for the detection of autoantibodies in patients with sAIBD. It may be of particular help in children and in elderly with poor venous access. PMID:29263541

New stroboscopic light source and technique for intraoperative retinal fluorescein angiography during penetrating keratoplasty

NASA Astrophysics Data System (ADS)

Krueger, Ronald R.; Morales, Ronald B.; Chong, Lawrence P.; Smith, Ronald E.

1994-06-01

We report the development of a new stroboscopic light source system and technique for performing intraoperative fluorescein angiography during penetrating keratoplasty for aphakic or pseudophakic bullous keratopathy. A controllable pulse xenon light source system with a fiber optic endoilluminator probe is used to perform high-quality intraoperative fluorescein angiography during penetrating keratoplasty in pigmented rabbits and human subjects. Following corneal trephination and extraction of the intraocular lens, a temporary Cobo keratoprosthesis is secured while a 20-gauge endoilluminator is inserted into the vitreous cavity through a limbal incision. The endoilluminator is advanced to a retinal illumination area of approximately 3 DD and 10% fluorescein is injected intravenously. A microscope camera coupled to a 50:50 beamsplitter photographs the passage of fluorescein dye while the surgeon maintains an unaltered view through the operating microscope. Angiograms through a keratoprosthesis show excellent contrast and resolution, comparable to standard fluorescein angiography. Fine peripapillary vessels are seen reproducibly and with great detail in the rabbits. All the phases of retinal angiography can be seen, including arteriolar constriction and capillary nonperfusion in one of four human subjects examined. High quality intraoperative fluorescein angiography can be performed in patients undergoing penetrating keratoplasty for aphakic/ pseudophakic bullous keratopathy. With this technology, preexisting retinal disorders such as cystoid macular edema might be identified in the perioperative setting allowing for important management decisions to be made intraoperatively.

[Toxic contact dermatitis from poison ivy in a private garden in Germany].

PubMed

Schauder, S; Callauch, R; Hausen, B M

2006-07-01

A couple suffered for 5 years from recurrent eruptions with vesicles and bullae after contact with an unknown "climbing weed" in their private garden in Germany. After this plant was identified as poison ivy and eradicated, their skin problems were solved. This is the first report of poison ivy in this setting. Urushiols in poison ivy are not only strong allergens but also potent irritants. Negative patch tests in the husband suggest that the bullous dermatitis was a toxic reaction.

Practical aspects of bacterial skin infections in children.

PubMed

Tunnessen, W W

1985-07-01

Bacterial skin infections are a common reason for children to be examined by a pediatrician. Streptococci and staphylococci are responsible for the great majority of the infections. Because of the variety of lesions produced by these bacteria, there is support for dividing impetigo into "traditional" crusted and bullous forms. Two important forms of cellulitis--facial and periorbital--have potential for serious systemic consequences. The bacterial etiology and treatment of cellulitis, animal bites, and puncture wounds of the foot require special attention for successful outcome.

Cross-reactions to desoximetasone and mometasone furoate in a patient with multiple topical corticosteroid allergies.

PubMed

Donovan, Jeffrey C H; Dekoven, Joel G

2006-09-01

A 60-year-old man developed a bullous contact dermatitis after topical corticosteroid treatment of dermatitis on his lower leg. Subsequent patch testing showed cross-reactions to numerous group B and group D corticosteroids as well as cross-reactions to group C desoximetasone and group D1 mometasone furoate. His patch-test result was negative for the group A corticosteroids hydrocortisone and tixocortol pivalate. We discuss the uncommon finding of cross-reactions to desoximetasone and mometasone furoate.

[Burning Vulva: Significance of Surgery in Inflammatory and Precancerous Vulvar Pathologies].

PubMed

Ghisu, Gian-Piero; Fink, Daniel

2015-06-17

Vuval pathologies manifested by allodynia and burning sensations can be due to infection, inflammatory dermatoses or other causes. Infective as well as certain inflammatory diseases, e.g. drug eruptions, allergic eczemas, irritative dermatitis/vulvitis, Behcet's Syndrome and pemphigus/pemphigoid usually respond well to conservative treatment. The category of inflammatory diseases also contains pathologies that in certain circumstances do require a surgical intervention, e.g. Lichen ruber planus/Lichen sclerosus, Condyloma, scars, premalignant lesions (VIN, genital M. Paget) and cancer. Vulodynia also can cause some stinging to the vulvar skin. The surgical aspects relating to the treatment of the benign and premalignant pathologies indicated above are mentioned in this mini-review.

The effect of autoimmune blistering diseases on work productivity.

PubMed

Wang, E Q; Radjenovic, M; Castrillón, M A; Feng, G H Y; Murrell, D F

2018-05-06

Autoimmune blistering diseases (AIBD) are known to negatively impact upon quality of life (QoL); however, there is a paucity of research on the effect of AIBD on work productivity. AIBD can be quite disfiguring in terms of a patient's appearance due to their blistering nature. To determine the impact of AIBD on work productivity and to determine whether patients are stigmatized at work due to their appearance. Sixty-one patients with AIBD completed the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAIQ-SHP), the Dermatology Life Quality Index (DLQI), the Autoimmune Bullous Disease Quality of Life (ABQOL) and the Treatment of Autoimmune Bullous Disease Quality of Life questionnaires (TABQOL). Non-responders to treatment had more work and activity impairment compared to responders. Worse WPAIQ-SHP scores were correlated with higher ABQOL, TABQOL and DLQI scores. Approximately 14.8% of subjects experienced stigmatization at work due to their appearance. The most common body areas stigmatized were easily visible sites, particularly the hands, arms and feet, with the majority of occurrences related to co-workers; for some patients, this stigmatization occurred on a daily basis. Loss of productivity at work was statistically much higher in those with higher disease severity, ABQOL & TABQOL scores and in non-responders to treatment. Autoimmune blistering diseases negatively impacts upon work productivity and activity. Stigmatization was common in the workplace which leads to increased stress, itself a stimulator of pemphigus. © 2018 European Academy of Dermatology and Venereology.

Dry eye and meibomian gland dysfunction in pseudophakic bullous keratopathy.

PubMed

Palamar, Melis; Kiyat, Pelin; Yagci, Ayse

2018-02-01

To evaluate dry eye tests and meibography of patients with pseudophakic bullous keratopathy (PBK). Thirty-seven patients with PBK were included. The eyes with PBK were compared with the normal pseudophakic fellow eyes. All patients had undergone a detailed ophthalmic examination including corneal and conjunctival fluorescein staining and Oxford scoring, tear film breakup time, Schirmer 1 test, Ocular Surface Disease Index (OSDI) score assessment, lid margin abnormalities, upper and lower eyelid Meibomian gland evaluation using infrared captures of a biomicroscope. Partial or complete loss of the Meibomian glands (Meibomian dropout) was scored for each eyelid from grade 0 (no loss) through grade 3 (lost area was > 2/3 of the total meibomian gland area). The mean age of the patients was 73.2 ± 8.9 (range, 50-93). Mean tear film breakup time value was statistically lower in PBK eyes (P ≤ 0.001). OSDI, Oxford, lid margin abnormalities, inferior meibography, total meibography score were significantly higher in PBK eyes (P ≤ 0.001). The comparison of Schirmer 1 and superior meibography scores of the groups was insignificant (P = 0.143, P = 0.793, respectively). The Meibomian gland morphology of the PBK eyes demonstrates significant differences when compared with normal fellow eyes and might be related to evaporative dry eye. For this reason, patients with PBK should be monitored for Meibomian gland dysfunction and when needed start prompt treatment in order to prevent further disturbance of the ocular surface.

Secondary angle closure caused by air migrating behind the pupil in descemet stripping endothelial keratoplasty.

PubMed

Lee, Jung S; Desai, Neel R; Schmidt, Gregory W; Jun, Albert S; Schein, Oliver D; Stark, Walter J; Eghrari, Allen O; Gottsch, John D

2009-07-01

To report secondary angle closure caused by air migrating behind the pupil in the context of intraocular pressure (IOP) elevation in the early postoperative period after Descemet stripping endothelial keratoplasty (DSEK). A retrospective case series was conducted on 100 consecutive DSEK cases from 90 patients undergoing DSEK because of corneal disease from Fuchs corneal dystrophy, pseudophakic bullous keratopathy, aphakic bullous keratopathy, and iridocorneal endothelial syndrome. Preoperative and postoperative slit-lamp examinations and IOP measurements were ascertained for all 100 eyes. Main outcome measures included preoperative and postoperative IOP. Thirteen of 100 eyes developed an IOP rise of greater than 30 mm Hg on the first postoperative day. Six of these 13 patients developed angle closure from air migrating posterior to the iris and causing iridocorneal adhesions. One of these 13 patients developed pupillary block from air anterior to iris. Six of 13 patients developed increased IOP without pupillary block or iridocorneal adhesions and had a history of preexisting primary or secondary glaucoma. A secondary angle closure associated with DSEK is reported with air migrating behind the iris, resulting in extensive iridocorneal adhesions. An acute increase in IOP after DSEK can also be induced by air anterior to the iris causing pupillary block. IOP spikes are much more common in the first few postoperative days after DSEK. Medical treatment can occasionally resolve air posterior to the iris, but if iridocorneal adhesions are extensive and persistent, air removal and angle reformation may be necessary.

In vivo laser confocal microscopy after non-Descemet's stripping automated endothelial keratoplasty.

PubMed

Kobayashi, Akira; Yokogawa, Hideaki; Sugiyama, Kazuhisa

2009-07-01

To investigate in vivo corneal changes in patients with bullous keratopathy who underwent non-Descemet's stripping automated endothelial keratoplasty (nDSAEK) with the use of laser confocal microscopy. Single-center, prospective clinical study. Ten eyes (10 patients; 3 men and 7 women; mean age, 73.5+/-6.6 years [mean+/-standard deviation]) with bullous keratopathy were evaluated in this study. In vivo laser confocal microscopy was performed before and 1, 3, and 6 months after nDSAEK. Selected confocal images of corneal layers were evaluated qualitatively and quantitatively for degree of haze and density of deposits. Before surgery, the following were observed in all patients: corneal epithelial edema, subepithelial haze, keratocytes in a honeycomb pattern, and tiny needle-shaped materials in the stroma. After nDSAEK, subepithelial haze, donor-recipient interface haze, and interface particles were observed in all measurable cases; postoperative haze, interface particles, and needle-shaped materials decreased statistically significantly (P<0.05) over the course of follow-up. In addition, hyperreflective giant interface particles were observed after nDSAEK in all patients. In vivo laser confocal microscopy can identify subclinical corneal abnormalities after nDSAEK such as subepithelial haze, host-recipient interface haze, host stromal needle-shaped materials, and host-recipient interface particles with characteristic giant particles. Further studies with this technology in a large number of patients and long-term follow-up are needed to understand fully the long-term corneal stromal changes after nDSAEK.

Human corneal endothelial cell transplantation using nanocomposite gel sheet in bullous keratopathy.

PubMed

Parikumar, Periasamy; Haraguchi, Kazutoshi; Senthilkumar, Rajappa; Abraham, Samuel Jk

2018-01-01

Transplantation of in vitro expanded human corneal endothelial precursors (HCEP) cells using a nanocomposite (D25-NC) gel sheet as supporting material in bovine's cornea has been earlier reported. Herein we report the transplantation of HCEP cells derived from a cadaver donor cornea to three patients using the NC gel sheet. In three patients with bullous keratopathy, one after cataract surgery, one after trauma and another in the corneal graft, earlier performed for congenital corneal dystrophy, not amenable to medical management HCEP cells isolated from a human cadaver donor cornea in vitro expanded using a thermoreversible gelation polymer (TGP) for 26 days were divided into three equal portions and 1.6 × 10 5 HCEP cells were injected on to the endothelium of the affected eye in each patient using the D25-NC gel sheet as a supporting material. The sheets were removed after three days. The bullae in the cornea disappeared by the 3 rd -11 th post-operative day in all the three patients. Visual acuity improved from Perception of light (PL)+/Projection of rays (PR)+ to Hand movements (HM)+ in one of the patients by post-operative day 3 which was maintained at 18 months follow-up. At 18 months follow-up, in another patient the visual acuity had improved from HM+ to 6/60 while in the third patient, visual acuity remained HM+ as it was prior to HCEP transplantation. There were no adverse effects during the follow-up in any of the patients.

ABCB1-Gen-Polymorphismus in einer polnischen Kohorte ist mit Risiko für bullöses Pemphigoid assoziiert.

PubMed

Rychlik-Sych, Mariola; Barańska, Małgorzata; Dudarewicz, Michał; Skrętkowicz, Jadwiga; Żebrowska, Agnieszka; Owczarek, Jacek; Waszczykowska, Elżbieta

2017-05-01

Polymorphismen im ABCB1-Gen, das für das P-Glykoprotein kodiert, können die intrazelluläre Konzentration von Xenobiotika beeinflussen und so zur Entwicklung von Autoimmunerkrankungen, einschließlich des bullösen Pemphigoids (BP), beitragen. In der vorliegenden Studie sollte untersucht werden, ob in einer polnischen Kohorte die C3435T- und G2677T/A-Polymorphismen im ABCB1-Gen mit dem Risiko für ein BP assoziiert sind. Die Studie umfasste 71 Patienten mit BP und 156 gesunde Probanden. Der C3435T-Polymorphismus wurde mittels PCR-RFLP bestimmt und der G2677T/A-Polymorphismus mittels Allel-spezifischer PCR. Es gab zwar keine Korrelation zwischen dem C3435-Polymorphismus und dem BP-Risiko, aber wir konnten eine derartige Assoziation hinsichtlich des G2677T/A-Polymorphismus nachweisen. Das relative Risiko eines BP war bei Personen mit dem 2677TA-Genotyp um mehr als den Faktor fünf erhöht (OR = 5,52; p = 0,0063) und bei Trägern des 2677TT-Genotyps mehr als verdoppelt (OR = 2,40; p = 0,0076). Mit 2,40 (p = 0,000018) war die OR bei Trägern des 2677T-Allels ebenfalls erhöht. Die höhere Prävalenz des 2677GG-Genotyps und des 2677G-Allels bei der Kontrollgruppe sowie eine OR < 1,0 (0,22 beziehungsweise 0,33) legen eine Schutzfunktion des 2677G-Allels hinsichtlich der Ausbildung eines BP nahe. Die Ergebnisse der vorliegenden Studie zeigen, dass der G2677T/A-Polymorphismus im ABCB1-Gen das Risiko für die Entstehung eines BP beeinflussen könnte. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Invasive Aspergillosis with Disseminated Skin Involvement in a Patient with Acute Myeloid Leukemia: A Rare Case

PubMed Central

Mert, Duygu; Iskender, Gülşen; Duygu, Fazilet; Merdin, Alparslan; Dal Mehmet, Sinan; Dogan, Mehmet; Tekgündüz, Emre; Ertek, Mustafa; Altuntaş, Fevzi

2017-01-01

Invasive pulmonary aspergillosis is most commonly seen in immunocompromised patients. Besides, skin lesions may also develop due to invasive aspergillosis in those patients. A 49-year-old male patient was diagnosed with acute myeloid leukemia. The patient developed bullous and zosteriform lesions on the skin after the 21st day of hospitalization. The skin biopsy showed hyphae. Disseminated skin aspergillosis was diagnosed to the patient. Voricanazole treatment was initiated. The patient was discharged once the lesions started to disappear. PMID:28626542

Bullous emphysema – Not always nicotine-related!

PubMed Central

Lüttecke-Hecht, Camilla; Hirche, Tim O.

2014-01-01

In a patient admitted for further investigation of haemoptysis and dyspnoea and known emphysema of the lung, a remarkable distribution of emphysematous bullae could be detected on CT-imaging. Further history, besides smoking, revealed apnoea diving-activity during younger adult age. The distinct appearance of partially septated pleura-based bullae lead to the suspicion of a positive-pressure barotrauma of the lungs in the past, now complicated by infection and bleeding. This case highlights the importance of thorough questioning of the patient and underlines the consideration of differential diagnoses of emphysema. PMID:26029539

Foreign body giant cells selectively covering haptics of intraocular lens implants: indicators of poor toleration?

PubMed

Wolter, J R

1983-10-01

A Sputnik lens implant removed after five years because of bullous keratopathy exhibits a dense covering of its Supramid anterior staves with large foreign body giant cells, while its Prolene loops and Polymethylmethacrylate optics have attracted only few of these cell units. The glass-membrane-like component of the reactive membrane also shows significant differences on the different parts of this implant. The use of observation of the components of reactive membranes on lens implants as indicators of toleration in the eye is suggested.

[Eosinophilic spongiosis and ICS antibodies in a child with strophulus-like dermatosis].

PubMed

Klein, G F; Hintner, H; Fristch, P O

1984-01-01

Eosinophilic spongiosis associated with in vivo-bound antibodies to the epidermal intercellular space (ICS) were consistently observed in a recurrent strophulus-like eruption in an 11-year-old boy, thus suggesting pemphigus. The clinical course, however, ruled this diagnosis out since neither acantholysis nor the clinical picture of pemphigus developed in a period of 2.5 years. Since in vivo-bound ICS-antibodies have been described in several case reports of bullous impetigo we speculate that immune reactions to bacterial antigens may be involved in producing eruptions mimicking pemphigus vulgaris.

Honey: A Natural Remedy for Eye Diseases.

PubMed

Majtanova, Nora; Cernak, Martin; Majtan, Juraj

2016-01-01

Honey has been considered as a therapeutic agent; its successful application in the treatment of non-healing infected wounds has promoted its further clinical usage for treating various disorders including eye disorders. There is evidence that honey may be helpful in treating dry eye disease, post-operative corneal edema, and bullous keratopathy. Furthermore, it can be used as an antibacterial agent to reduce the ocular flora. This review discusses both the current knowledge of and new perspectives for honey therapy in ophthalmology. © 2016 S. Karger GmbH, Freiburg.

Acantholytic dermatosis of the vulva.

PubMed

Mansura, Adva; Maly, Alexander; Ramot, Yuval; Zlotogorski, Abraham

2015-05-18

Acantholytic dermatosis of the vulva is a rare condition, presenting with papular eruption in the genital area without history of Darier disease or Hailey-Hailey disease. We report a case with a papular pruritic eruption in the region of the vulva, coalescing into plaques. Biopsy specimen showed irregular acanthosis with an area of split-like bullous formation in the deeper part of the epidermis, as well as acantholytic cells, marked hypergranulosis and hyperkeratosis, compatible with the rare diagnosis of acantholytic dermatosis of the vulva. We review the clinical and histological characteristics of this uncommon disease.

Autoimmune myelofibrosis with pancytopenia as a presenting manifestation of systemic lupus erythematosus responsive to mycophenolate mofetil.

PubMed

Ungprasert, P; Chowdhary, V R; Davis, M D; Makol, A

2016-04-01

Hematological abnormalities, such as anemia, leucopenia, and thrombocytopenia, secondary to peripheral destruction, are common in systemic lupus erythematosus (SLE). However, cytopenias from autoimmune myelofibrosis (AIMF) are extremely uncommon in SLE, with less than 40 reported cases in the literature. We report the case of a 33-year-old female who presented with bullous skin lesions and pancytopenia as the presenting manifestation of what was ultimately diagnosed as SLE with AIMF. She responded well to glucocorticoids and mycophenolate mofetil. © The Author(s) 2015.

[Dermatology day-care: between official rules and reality].

PubMed

Ingen-Housz-Oro, S; Durand-Zaleski, I; Cosnes, A; Valeyrie-Allanore, L; Moreno, J-C; Chosidow, O; Wolkenstein, P

2012-11-01

Official rules published in 2006 and 2010 concerning ambulatory care rates in France led to artificial redistribution of this activity from day-care hospitalization to consultations. In our dermatological day-care establishment, we compared the financial costs engendered for patients admitted for day-care hospitalization and those seen at consultations. From 2011/01/10 to 2011/02/04, for each patient, we prospectively analyzed the following data: day-care hospitalization or consultation, age, sex, diagnosis, laboratory and radiological examination, non-dermatological consultations, time spent with the patient by doctors (interns, senior doctors) and nurses, with timing by a stop-watch. The hospital cost was the total for medical examinations (official nomenclature), non-dermatological consultations, physicians' and nurses' salaries and establishment overheads (216 €). The hospital revenue regarding the consultation group consisted of the sum of reimbursement for medical examination, dermatological and non-dermatological consultations, and regarding the day-care hospitalization group, the dermatology rate (670 €) or chemotherapy sessions (380 €). Results were compared using a Chi(2) test and a Student's t-test (P ≤ 0.05). One hundred and twenty-seven patients were included: 67 in the day-care hospitalization group and 60 in the consultation group. Patients in the day-care hospitalization group were older and had significantly more radiological examinations and non-dermatological consultations, but the number of laboratory examinations and skin biopsies did not differ between the two groups. The mean time spent by doctors was similar in both groups but the time spent by senior doctors without the help of interns was significantly greater and longer than the time for a standard consultation. Nurses spent a mean 72 minutes with each hospitalized patient and 35 minutes with consultation patients (P = 0.007). Hospital costs were identical in both groups at around 415 €. The hospital showed a profit for day-care hospitalization patients (252 €) and a loss (244 €) for consultation patients. Half of the patients studied were in day-care hospitalization and half were seen in consultations. The high number of bed-ridden patients with bullous pemphigoid accounts for the fact that day-care patients were older. The reasons for the significantly longer time spent by nurses with day-care hospitalized patients were administration and supervision of chemotherapy, skin care and nursing of bed-ridden patients. However, nurses spent 35 min with each consultation patient, justifying the need to maintain the posts of these staff in such day-care units. The availability of physicians for patients with severe dermatoses and the organization of medical examinations in the same place in the same day underscore the need for medical structures like day-care hospitalization. At present, time spent on intellectual work involving reflection is regrettably not taken into account, which is detrimental to this specialty. The hospital was in profit for day hospitalizations while consultations resulted in losses, in particular because of the absence of social security reimbursement of the establishment's overheads. Rules are in need of modification in order to allow the treatment of patients with more complicated conditions. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Pruritic folliculitis of pregnancy.

PubMed

Delorenze, Lilian Mathias; Branco, Letícia Guedes; Cerqueira, Luiza Fiszon; Vasques, Wellington Batista; Salles, Simone de Abreu Neves; Vilar, Enoi Guedes

2016-01-01

Pruritic folliculitis of pregnancy is a rare disease of unknown etiology. It occcurs primarily during pregnancy, usually with spontaneous resolution postpartum. It is characterized by a benign dermatosis, with papular and pustular follicular lesions that first appear on the torso and occasionally spread throughout the body. We report the case of a patient in the 27th week of pregnancy, with a two-month evolution of pruritic and papular erythematous lesions on her lower back. Differential diagnosis includes other pregnancy-specific dermatoses: gestational pemphigoid, pruritic urticarial papules and plaques of pregnancy (PUPPP), prurigo of pregnancy, and (PUPPP) and prurigo of pregancy. Histopathological tests showed changes consistent with pruritic folliculitis of pregnancy. This case is relevant due to its rare nature and its clinical and histopathological characteristics.

Pruritic folliculitis of pregnancy*

PubMed Central

Delorenze, Lilian Mathias; Branco, Letícia Guedes; Cerqueira, Luiza Fiszon; Vasques, Wellington Batista; Salles, Simone de Abreu Neves; Vilar, Enoi Guedes

2016-01-01

Pruritic folliculitis of pregnancy is a rare disease of unknown etiology. It occcurs primarily during pregnancy, usually with spontaneous resolution postpartum. It is characterized by a benign dermatosis, with papular and pustular follicular lesions that first appear on the torso and occasionally spread throughout the body. We report the case of a patient in the 27th week of pregnancy, with a two-month evolution of pruritic and papular erythematous lesions on her lower back. Differential diagnosis includes other pregnancy-specific dermatoses: gestational pemphigoid, pruritic urticarial papules and plaques of pregnancy (PUPPP), prurigo of pregnancy, and (PUPPP) and prurigo of pregancy. Histopathological tests showed changes consistent with pruritic folliculitis of pregnancy. This case is relevant due to its rare nature and its clinical and histopathological characteristics. PMID:28300898

Descemet membrane endothelial keratoplasty in cases with existing scleral-sutured and iris-sutured intraocular lenses

PubMed Central

2014-01-01

Background To report two cases of Descemet Membrane Endothelial Keratoplasty (DMEK) in patients with existing scleral-fixated and iris-fixated intraocular lenses (sf-IOL and if-IOL, respectively). Case presentation DMEK procedures were performed on a 49-year-old woman with a pre-existing sf-IOL (case 1) and a 69-year-old woman with a pre-existing if-IOL (case 2) in order to treat secondary corneal edema due to pseudophakic bullous keratopathy. Visual acuity, refractive error, intraocular pressure, slit lamp examination, pachymetry measurements and endothelial cell density (ECD) were considered and repeated during follow-ups. Both cases had no intraoperative complications. At postoperative day 1 graft centration and complete attachment were noted. The IOL positions were unchanged in comparison to their preoperative positions. In case 1, visual acuity improved from 1/15 at 1 meter preoperative to 20/200 within one week and to 20/63 within 12 weeks of follow up. In case 2, visual acuity improved from counting fingers at 1 meter preoperative to 20/200 within one week and to 20/100 within 12 weeks of follow-up. In case 2 a partial graft dislocation was observed at postoperative day twenty. Complete graft re-apposition was achieved by rebubbling procedure performed with intracameral air injection. Conclusions DMEK surgery in the treatment of pseudophakic bullous keratopathy in the presence of sf-IOL and if-IOL can successfully be performed. These eyes are at increased risk of IOL dislocation into the vitreous cavity during DMEK surgery. PMID:24443809

Viscoelastic-Assisted Non-Descemet Stripping Automated Endothelial Keratoplasty in Vitrectomized and Iris-Lens Diaphragm Injured Eyes.

PubMed

Ren, Yueping; Zhao, Zelin; Shao, Yumei; Waller, Stephen G; Jhanji, Vishal; Chen, Wei

2015-11-01

To report the outcomes of viscoelastic-aided non-Descemet stripping automated endothelial keratoplasty (nDSAEK) to treat bullous keratopathy in vitrectomized and iris-lens diaphragm injured eyes. A prospective consecutive case series of eyes with bullous keratopathy underwent nDSAEK. About 0.15 to 0.2 mL cohesive viscoelastic was injected into the anterior chamber in front of the iris defect to prevent air from entering the posterior chamber and vitreous cavity. Filtered air was injected until the intraocular pressure (IOP) rose to a mildly high level. Graft position and complications were monitored postoperatively. Endothelial cell density and best-corrected visual acuity (BCVA) were recorded at a 1-year follow-up. Viscoelastic-aided nDSAEK was performed in 21 cases (11 males, 10 females; mean age: 58.9±12.4 years). No intraoperative complications were noted. Effective graft adherence was achieved in all cases intraoperatively. Postoperatively, partial graft dislocation was seen in 2 cases because of hypotony (IOP, 6 and 5 mm Hg, respectively) due to postoperative cyclodialysis as demonstrated on anterior segment optical coherence tomography. Hypotony was successfully managed conservatively with spontaneous graft reattachment. One year postoperatively, the median BCVA improved to 20/50. The mean endothelial cell loss was 14.7±12.6% and 20.5±11.1% at 6 months and 1 year, respectively. In vitrectomized and iris-lens diaphragm injured eyes, viscoelastic-aided nDSAEK effectively facilitated graft adherence and reduced graft dislocation. Appropriate control of IOP was considered to play a vital role in supporting the graft adherence.

Minor Salivary Gland Transplantation for Severe Dry Eyes.

PubMed

Wakamatsu, Tais Hitomi; SantʼAnna, Ana Estela Besteti Pires Ponce; Cristovam, Priscila Cardoso; Alves, Venâncio Avancini Ferreira; Wakamatsu, Alda; Gomes, José Alvaro Pereira

2017-11-01

Dry eye is a multifactorial disease comprising a wide spectrum of ocular surface alterations and symptoms of discomfort. In most patients with aqueous-deficient dry eye, pharmaceutical tear substitutes are used to control symptoms and prevent ocular surface damage. However, in severe dry eye conditions caused by cicatricial disorders, such as Stevens-Johnson syndrome and ocular cicatricial mucous membrane pemphigoid, noninvasive treatments are insufficient, and patients are at risk of developing complications that can lead to blindness. The use of salivary glands as a source of lubrication to treat severe cases of dry eye has been proposed by different authors. The first reports proposed parotid or submandibular gland duct transplantation into the conjunctival fornix. However, complications limited the functional outcomes. Minor salivary gland autotransplantation together with labial mucosa has been used as a complex graft to the conjunctival fornix in severe dry eye with a good outcome. Our group demonstrated significant improvements in best-corrected visual acuity, Schirmer I test score, corneal transparency, and neovascularization after using this technique. A symptoms questionnaire applied to these patients revealed improvements in foreign body sensation, photophobia, and pain. Similar to tears, saliva has a complex final composition comprising electrolytes, immunoglobulins, proteins, enzymes, and mucins. We demonstrated the viability of minor salivary glands transplanted into the fornix of patients with dry eye by performing immunohistochemistry on graft biopsies with antibodies against lactoferrin, lysozyme, MUC1, and MUC16. The findings revealed the presence of functional salivary gland units, indicating local production of proteins, enzymes, and mucins.

[Hand management in recessive dystrophic bullous epydermolysis].

PubMed

Pajardi, G; Novelli, C; Parolo, C; Proserpio, G; Tegon, M; Vecchi, S

2011-01-01

Recessive distrofic epidermolysis bullosa creates severe hand deformities with disabling functional limitations. Hand surgeon should perform surgery when deformity inibits function, in order to restore the pinch. We present our experience on 44 patients and 58 operated hands, with the following schema: hand degloving, grafting of the first web and intraoperative dynamic splinting. In 30 patient with an 8 years follow up, 25 had had good or excellent results, and the 5 remaining shows early recurrence. Association of a correct surgical approach and adequate intra and post-operative rehabilitation improve hand function and a slow down inevitable recurrence.

Bilateral exudative retinal detachment associated with central serous chorioretinopathy in a patient treated with corticosteroids.

PubMed

Rueda-Rueda, T; Sánchez-Vicente, J L; Llerena-Manzorro, L; Medina-Tapia, A; González-García, L; Alfaro-Juárez, A; Vital-Berral, C; López-Herrero, F; Muñoz-Morales, A; Ortega, L S; Herrador-Montiel, Á

2017-10-01

The case is presented on a 54-year-old woman with a central serous chorioretinopathy, misdiagnosed as Vogt-Koyanagi-Harada disease, and treated with systemic corticosteroids. The patient presented with a bilateral bullous exudative retinal detachment. Discontinuation of corticosteroid therapy, surgical drainage of subretinal fluid, and photodynamic therapy, led to anatomical and functional improvement. The recognition of an atypical presentation of central serous chorioretinopathy may avoid complications of the inappropriate treatment with corticosteroids. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Advanced Diagnostic Techniques in Autoimmune Bullous Diseases

PubMed Central

Jindal, Anuradha; Rao, Raghavendra; Bhogal, Balbir S

2017-01-01

Autoimmune blistering diseases are diverse group of conditions characterized by blisters in the skin with or without mucosal lesions. There may be great degree of clinical and histopathological overlap; hence, advanced immunological tests may be necessary for more precise diagnosis of these conditions. Direct immunofluorescence microscopy is the gold standard tests to demonstrate the tissue-bound antibodies and should be done in all cases. Magnitude of antibody level in patient’ serum can be assessed by indirect immunofluorescence and enzyme linked immunosorbent assay. In this article we have reviewed the various techniques that are available in the diagnosis of autoimmune blistering diseases. PMID:28584369

Autoimmunity and autoimmune co-morbidities in psoriasis.

PubMed

Furue, Kazuhisa; Ito, Takamichi; Tsuji, Gaku; Kadono, Takafumi; Nakahara, Takeshi; Furue, Masutaka

2018-05-01

Psoriasis is characterized by widespread scaly erythematous plaques that cause significant physical and psychological burdens for the affected individuals. Accelerated inflammation driven by the tumour necrosis factor-α/interleukin-23/interleukin-17 axis is now known to be the major mechanism in the development of psoriasis. In addition, psoriasis has an autoimmune nature that manifests as autoreactive T cells and is co-morbid with other autoimmune diseases, such as autoimmune bullous diseases, vitiligo, alopecia and thyroiditis. In this article, we review the recent topics on autoimmunity and autoimmune co-morbidities in psoriasis. © 2018 John Wiley & Sons Ltd.

Acantholysis revisited: back to basics.

PubMed

Seshadri, Divya; Kumaran, M Sendhil; Kanwar, Amrinder J

2013-01-01

Acantholysis means loss of coherence between epidermal cells due to the breakdown of intercellular bridges. It is an important pathogenetic mechanism underlying various bullous disorders, particularly the pemphigus group, as well as many non-blistering disorders. Although a well-known concept, the student often has to refer to many sources to comprehend acantholysis completely. Thorough knowledge of this topic helps in clinching many diagnoses. The etiopathogenesis, classification, clinical signs, and laboratory demonstration of acantholysis are discussed in detail to help students build clear concepts. We have focused on various distinguishing points in different disorders for an easy grasp of the topic.

Young donor-graft assisted endothelial keratoplasty (PDEK/DMEK) with epithelial debridement for chronic pseudophakic bullous keratopathy.

PubMed

Agarwal, Amar; Narang, Priya; Kumar, Dhivya A; Agarwal, Ashvin

2017-10-01

The aim of this study was to describe the applicability and report visual outcomes for the treatment of subepithelial fibrosis and anterior stromal scarring in cases of chronic pseudophakic bullous keratopathy (PBK) with epithelial debridement and endothelial keratoplasty (EK) (pre-Descemet endothelial keratoplasty [PDEK]; Descemet membrane endothelial keratoplasty [(DMEK]) using young donor tissue. Prospective, single-centre, interventional study. 6 cases with chronic PBK (> 1 year duration). Case 1 underwent PDEK with glued intraocular lens (IOL) as a single-stage procedure, whereas cases 2 and 3 underwent glued IOL followed by DMEK and PDEK, respectively, as a second-stage procedure. Cases 4 and 6 underwent PDEK, whereas case 5 underwent DMEK. Epithelial debridement was performed in all cases at the time of EK, and young donor grafts were used. The main outcome measures were best spectacle-corrected visual acuity, clearance of corneal scar and haze, central corneal thickness (CCT), specular microscopy, and endothelial cell count (ECC). Postoperatively, all cases demonstrated significant improvement in visual acuity. The mean value of depth of subepithelial haze was 121±71.7 µm and 25.3 ± 19.8 µm in the preoperative and postoperative periods, respectively (p = 0.028). At the 1-month follow-up, the mean preoperative CCT of 676 ± 92.7 µm was reduced to 534.6 ± 21.1µm. At the 6-month follow-up, the mean ECC loss resulting from the procedure was 36.5 ± 10.4%. EK with epithelial debridement performed for the treatment of chronic PBK resulted in significantly improved visual acuity to a functional level, with the clearance of subepithelial fibrosis and anterior stromal scar, in most patients. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

[Personalized cell therapy for early postoperative bullous keratopathy (experimental proof and clinical results)].

PubMed

Kasparov, A A; Kasparova, Evg A; Fadeeva, L L; Subbot, A M; Borodina, N V; Kasparova, E A; Kobzova, M V; Musaeva, G M; Pavliuk, A S

2013-01-01

The article presents the results of a long-term research on development and clinical application of personalized cell therapy (PCT) for treatment of early postoperative (manifesting within the first 3 months after surgery) bullous keratopathy (BK). The method of intracameral PCT implies in vitro incubation of the patient's blood sample with poly(A:U) stimulator, separation of the serum with activated leukocytes, and injection of the final cell preparation into the anterior chamber. The fundamental part of the research was aimed at a detailed description of the cell preparation and investigation of its possible mechanisms of action. Cytokine and growth factor level in the cell preparation suggested that its high clinical efficacy might be due to its ability to improve regeneration of damaged corneal endothelium. The clinical study was conducted on a group of 52 patients with early BK. A significant effect (smoothing of the Descement's membrane folds, complete resorption of corneal edema, improvement of corneal transparency, reduction of corneal thickness and increase of visual acuity by 0.49 +/- 0.27) was achieved in 44.2% of patients, while partial effect was seen in 21.1% of patients. There was no clinical effect in 34.6% of patients. In those patients who developed significant or partial clinical effect after the PCT, many endotheliocytes appeared to have multiple nuclei (2 and more). In some patients polyploid nuclei persisted for 3-5 years after the treatment. Polyploidy results from incomplete mitosis which might be due to regenerative processes in the endothelium stimulated by the PCT. Obviously, high efficacy and relative simplicity of the method should promote its further clinical introduction.

Systemic lupus erythematosus-associated neutrophilic dermatosis--an underrecognized neutrophilic dermatosis in patients with systemic lupus erythematosus.

PubMed

Larson, Allison R; Granter, Scott R

2014-03-01

Neutrophilic dermatoses are an uncommon manifestation of lupus. We describe the clinical and histopathologic features of 14 patients with systemic lupus erythematosus (SLE) and neutrophilic dermatoses, 2 of whom had no prior history of SLE. Thirteen patients were female, ranging in age from 27 to 62 years (mean age, 42.8 years). One patient was a 20-year-old man. Most lesions were described as erythematous papules and plaques and showed annular morphology in 6 patients and a photodistribution in 2 patients. Histopathologic examination in all cases showed an interstitial neutrophilic infiltrate with leukocytoclasis that ranged from sparse in 5 cases and moderate to dense in 9 cases. With one exception, those cases with moderate to dense infiltrates resembled Sweet's syndrome at scanning magnification. Two cases resembled bullous SLE, and 1 case showed overlapping features of bullous SLE and Sweet's syndrome. Interface changes were seen in 8 patients, which were subtle and vacuolar in 7. One case was associated with a florid interface tissue reaction. Dermal mucin was seen in 4 cases and was a prominent feature in only one of these. One case showed a minute discrete focus resembling palisaded neutrophilic and granulomatous dermatitis. It is important to consider SLE-associated neutrophilic dermatosis in the differential diagnosis of neutrophilic tissue reactions particularly because some patients will have no prior history of lupus. It is also important to be aware of the broad histologic spectrum that may be encountered in SLE-associated neutrophilic dermatosis, ranging from subtle paucicellular lesions to florid Sweet's-like lesions associated with a dense neutrophilic infiltrate. Copyright © 2014 Elsevier Inc. All rights reserved.

Co-localisation of advanced glycation end products and D-β-aspartic acid-containing proteins in gelatinous drop-like corneal dystrophy.

PubMed

Kaji, Yuichi; Oshika, Tetsuro; Takazawa, Yutaka; Fukayama, Masashi; Fujii, Noriko

2012-08-01

Gelatinous drop-like corneal dystrophy (GDLD), also known as familial subepithelial corneal amyloidosis, is an autosomal recessive disorder that causes progressive corneal opacity due to accumulation of amyloid fibrils in the corneal stroma. Genetic analyses have revealed that a mutation in membrane component chromosome 1 surface marker 1 gene is responsible for GDLD. However, the mechanism of amyloid formation in the corneal stroma remains unclear. The present study attempted to reveal the role of advanced glycation end products (AGE) and d-amino acids in amyloid formation in GDLD. Informed consent was obtained from five patients with GDLD, three patients with bullous keratopathy and three patients with interstitial keratitis and all the specimens were analysed. Localisation of amyloid fibrils was analysed using Congo-red and thioflavin T staining. In addition, the localisation of AGE (N(ε)-carboxy(methyl)-L-lysine, pyrraline and pentosidine) and D-β-aspartic acid-containing proteins, a major form of d-amino acid-containing proteins, was analysed immunohistochemically. In all GDLD specimens, strong immunoreactivity to AGE and D-β-aspartic acid-containing proteins was detected in the subepithelial amyloid-rich region. In contrast, amyloid fibrils, AGE, or D-amino acid-containing proteins were slightly detected in the corneal stroma of patients with bullous keratopathy and interstitial keratitis. Abnormally accumulated proteins rich in AGE and D-β-aspartic acid co-localise in the amyloid lesions in GDLD. These results indicate that non-enzymatic post-translational modifications of proteins, including AGE formation and isomerisation of aspartyl residues, will be the cause as well as the result of amyloid fibril formations in GDLD.

Co-localisation of advanced glycation end products and d-β-aspartic acid-containing proteins in gelatinous drop-like corneal dystrophy

PubMed Central

Oshika, Tetsuro; Takazawa, Yutaka; Fukayama, Masashi; Fujii, Noriko

2012-01-01

Purpose Gelatinous drop-like corneal dystrophy (GDLD), also known as familial subepithelial corneal amyloidosis, is an autosomal recessive disorder that causes progressive corneal opacity due to accumulation of amyloid fibrils in the corneal stroma. Genetic analyses have revealed that a mutation in membrane component chromosome 1 surface marker 1 gene is responsible for GDLD. However, the mechanism of amyloid formation in the corneal stroma remains unclear. The present study attempted to reveal the role of advanced glycation end products (AGE) and d-amino acids in amyloid formation in GDLD. Methods Informed consent was obtained from five patients with GDLD, three patients with bullous keratopathy and three patients with interstitial keratitis and all the specimens were analysed. Localisation of amyloid fibrils was analysed using Congo-red and thioflavin T staining. In addition, the localisation of AGE (Nɛ-carboxy(methyl)-l-lysine, pyrraline and pentosidine) and d-β-aspartic acid-containing proteins, a major form of d-amino acid-containing proteins, was analysed immunohistochemically. Results In all GDLD specimens, strong immunoreactivity to AGE and d-β-aspartic acid-containing proteins was detected in the subepithelial amyloid-rich region. In contrast, amyloid fibrils, AGE, or d-amino acid-containing proteins were slightly detected in the corneal stroma of patients with bullous keratopathy and interstitial keratitis. Conclusions Abnormally accumulated proteins rich in AGE and d-β-aspartic acid co-localise in the amyloid lesions in GDLD. These results indicate that non-enzymatic post-translational modifications of proteins, including AGE formation and isomerisation of aspartyl residues, will be the cause as well as the result of amyloid fibril formations in GDLD. PMID:22694960

Evolving indications for and trends in keratoplasty in British Columbia, Canada, from 2002 to 2011: a 10-year review.

PubMed

Tan, Johnson C H; Holland, Simon P; Dubord, Paul J; Moloney, Gregory; McCarthy, Martin; Yeung, Sonia N

2014-03-01

The aim of this study was to report the evolving indications for keratoplasty and the shift in the type of keratoplasty performed in British Columbia, Canada, over a 10-year period from 2002 to 2011. This was a retrospective database review of all the records of corneal transplant tissues at the Eye Bank of British Columbia, Canada, from January 2002 to December 2011. The patient demographics, indications, and types of transplant performed were analyzed. A total of 4843 corneal transplants were performed in 3742 patients (1968 male and 1774 female) from January 2002 to December 2011. The number of keratoplasties performed ranged from 420 in 2008 to 578 in 2011. The top 4 indications over the 10-year period were Fuchs endothelial dystrophy (FED; 18.9%), aphakic/pseudophakic bullous keratopathy (17.4%), regraft (17.1%), and keratoconus (15.5%). Penetrating keratoplasty (PKP) accounted for 86.5% (4191 transplants) of all keratoplasties performed. Since the introduction of Descemet stripping automated endothelial keratoplasty (DSAEK) in 2007, there was a significant increase in the number of DSAEKs (P < 0.0001) performed and a statistical decline in the number of PKPs (P < 0.0001) performed. Despite only 30 deep anterior lamellar keratoplasties being performed, an increasing trend was observed after 2008 (P = 0.0087). A decreasing trend in PKPs and an increasing trend in DSAEKs were observed for surgeries performed for FED, aphakic/pseudophakic bullous keratopathy, and regraft. FED has become the top indication for performing a keratoplasty over the 10-year period. There was a shift from PKP to DSAEK performed for endothelial failure. Although the number of deep anterior lamellar keratoplasty surgeries was small, there was a significant increasing trend.

Topographic hot spot before descemet stripping automated endothelial keratoplasty is associated with postoperative hyperopic shift.

PubMed

Shimizu, Tsutomu; Yamaguchi, Takefumi; Satake, Yoshiyuki; Shimazaki, Jun

2015-03-01

The aim of this study was to investigate topographic "hot spots" on the anterior corneal surface before Descemet stripping automated endothelial keratoplasty (DSAEK) and their effects on postoperative visual acuity and hyperopic shift. Twenty-seven eyes of 27 patients with bullous keratopathy, who underwent DSAEK were studied. We defined a hot spot as a focal area with relatively high refractive power on the anterior corneal surface in eyes with bullous keratopathy. Refractive spherical equivalent, keratometric value, and corneal topography were retrospectively evaluated using anterior segment optical coherence tomography (AS-OCT). Hot spots were identified in 11 eyes (42.3%) before DSAEK and disappeared in 9 eyes of these eyes (81.8%) at 6 months after DSAEK. AS-OCT revealed focal epithelial thickening in the same areas as the hot spots. There was no significant difference in the postoperative visual acuity between eyes with and without hot spots (P > 0.05). The keratometric value of the anterior corneal surface significantly flattened from 45.7 ± 2.7 diopters (D) before DSAEK to 44.2 ± 2.7 D 1 month after DSAEK in eyes with hot spots (P = 0.01), whereas in eyes without hot spots, there were no significant differences in the keratometric values before and after DSAEK. At 6 months, the refractive change was +1.1 ± 1.3 D in eyes with hot spots and -0.2 ± 0.6 D in eyes without hot spots (P = 0.034). In eyes with focal epithelial thickening, topographic hot spots on the anterior corneal surface were observed using AS-OCT. The hot spots disappeared after DSAEK and had no influence on the postoperative visual acuity.

Accurate heterogeneous dose calculation for lung cancer patients without high‐resolution CT densities

PubMed Central

Li, Jonathan G.; Liu, Chihray; Olivier, Kenneth R.; Dempsey, James F.

2009-01-01

The aim of this study was to investigate the relative accuracy of megavoltage photon‐beam dose calculations employing either five bulk densities or independent voxel densities determined by calibration of the CT Houndsfield number. Full‐resolution CT and bulk density treatment plans were generated for 70 lung or esophageal cancer tumors (66 cases) using a commercial treatment planning system with an adaptive convolution dose calculation algorithm (Pinnacle3, Philips Medicals Systems). Bulk densities were applied to segmented regions. Individual and population average densities were compared to the full‐resolution plan for each case. Monitor units were kept constant and no normalizations were employed. Dose volume histograms (DVH) and dose difference distributions were examined for all cases. The average densities of the segmented air, lung, fat, soft tissue, and bone for the entire set were found to be 0.14, 0.26, 0.89, 1.02, and 1.12 g/cm3, respectively. In all cases, the normal tissue DVH agreed to better than 2% in dose. In 62 of 70 DVHs of the planning target volume (PTV), agreement to better than 3% in dose was observed. Six cases demonstrated emphysema, one with bullous formations and one with a hiatus hernia having a large volume of gas. These required the additional assignment of density to the emphysemic lung and inflammatory changes to the lung, the regions of collapsed lung, the bullous formations, and the hernia gas. Bulk tissue density dose calculation provides an accurate method of heterogeneous dose calculation. However, patients with advanced emphysema may require high‐resolution CT studies for accurate treatment planning. PACS number: 87.53.Tf

[Differential diagnosis of febrile exanthema].

PubMed

Aramă, St S; Anca, Ioana Alina; Munteanu, Daniela-Ioana; Aramă, Victoria; Hristea, Adriana; Moroti, Ruxandra; Ion, Daniela Adriana

2007-01-01

Febrile exanthema (FE) is an extremely polymorphous clinical entity, frequently seen in daily clinical practice. FE is characterized by diffuse rash and fever. FE is classified in 4 types, depending on the primary skin lesion: macular, maculopapular, vesicular, and bullous exanthema. It is of infectious and non-infectious cause. Among the infectious causes the most frequent is the viral one. FE may affect all ages, but especially children and young people. Usually, FE raises important issues of differential diagnosis, because its clinical and etiological complexity. To decide the most appropriate therapeutic and prophylactic measures for FE, it is important to know the clinical criteria and the specific diagnostic methods.

[Kindler syndrome. A new bullous dermatosis].

PubMed

Has, C

2009-08-01

The Kindler syndrome is a new form of inherited epidermolysis bullosa and the first genodermatosis caused by a defect of the focal adhesions. Kindlin-1, the deficient protein, plays an essential role in integrin activation and in the adhesion of keratinocytes to the extracellular matrix. The adhesion defect leads to skin blistering which begins at birth and ameliorates with age, and to mucosal fragility which leads to scarring and stricture formation. Skin atrophy and poikiloderma develop progressively. Photosensitivity is rather mild, but squamous cell carcinomas develop on sun-exposed areas mainly after the age of 40 years. The most important differential diagnoses are epidermolysis bullosa with mottled pigmentation and dystrophic epidermolysis bullosa. Management aims to treat the symptoms and prevent complications.

Pregnancy and delivery with Kindler syndrome.

PubMed

Hayashi, Shusaku; Shimoya, Koichiro; Itami, Satoshi; Murata, Yuji

2007-01-01

Kindler syndrome is a rare, autosomal-recessive skin disease characterized by bullous poikiloderma. Mucosal manifestations are common that involve the oral cavity, esophagus, urethra and genital organs. A 37-year-old woman with Kindler syndrome received prenatal care at our hospital. Her skin disease did not change during pregnancy and puerperium. Her pregnancy course was uneventful, but an elective cesarean section was performed at 38 weeks of gestation due to vaginal stenosis. Surgical wound healing was uncomplicated. Pregnancy did not exacerbate the cutaneous symptoms of Kindler syndrome in this case. Cesarean delivery may be necessary in cases with severe genital lesions besides obstetrical indications. Careful perioperative management is needed to protect vulnerable skin and mucosa. 2007 S. Karger AG, Basel

Stevens-Johnson syndrome in childhood.

PubMed

Blanco, N; Gutiérrez, B; Valls, I; Puertas, D; Martín, C; Rivera, M; Hernández, Á; Torrelo, A

2017-05-01

Stevens-Johnson syndrome and toxic epidermal necrolysis are two serious immune diseases within the context of bullous mucocutaneous syndrome. These have varying degrees of involvement of the skin and usually at least two mucous membranes. Three clinical cases are presented, two of them with significant ophthalmological sequelae, who had received drug treatment as a possible trigger, and another milder clinical case caused by Mycoplasma pneumoniae. The ophthalmologist plays a crucial role in the outcome and eye care of the patient in order to try to avoid the appearance of sequelae and subsequent loss of vision. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Serratia marcescens Bullous Cellulitis in a Splenectomized Patient: A Case Report and Review of the Literature.

PubMed

Fournier, John B; Dabiri, Ganary; Thomas, Vinod; Skowron, Gail; Carson, Polly; Falanga, Vincent

2016-06-01

Serratia marcescens is a Gram-negative bacillus belonging to the Enterobacteriaceae family. Cutaneous infection with Serratia is rare, and usually occurs in immunocompromised individuals. Primary cutaneous infections are uncommon, but they are typically severe and are associated with significant morbidity and mortality. The pathogenetic factors leading to S. marcescens infection are not fully understood, but contributing virulence factors include proteases, secreted exotoxins, and the formation of biofilm. We report a case of cellulitis occurring in a splenectomized patient, which led to multiple wound debridements and a transmetatarsal amputation. This dramatic case led us to review the published literature on soft tissue infections caused by S. marcescens. © The Author(s) 2016.

Oral lichenoid lesions: distinguishing the benign from the deadly.

PubMed

Müller, Susan

2017-01-01

Oral lichen planus is a chronic inflammatory disease of unknown etiology or pathogenesis with varied disease severity that waxes and wanes over a long period of time. Although a common oral mucosal disease, accurate diagnosis is often challenging due to the overlapping clinical and histopathological features of oral lichen planus and other mucosal diseases. Other immune-mediated mucocutaneous diseases can exhibit lichenoid features including mucous membrane pemphigoid, chronic graft-versus-host disease, and discoid lupus erythematosus. Reactive changes to dental materials or to systemic medications can mimic oral lichen planus both clinically and histologically. In these situations the clinical presentation can be useful, as oral lichen planus presents as a multifocal process and is usually symmetrical and bilateral. Dysplasia of the oral cavity can exhibit a lichenoid histology, which may mask the potentially premalignant features. Proliferative verrucous leukoplakia, an unusual clinical disease, can often mimic oral lichen planus clinically, requiring careful correlation of the clinical and pathologic features.

Decorin and biglycan of normal and pathologic human corneas

NASA Technical Reports Server (NTRS)

Funderburgh, J. L.; Hevelone, N. D.; Roth, M. R.; Funderburgh, M. L.; Rodrigues, M. R.; Nirankari, V. S.; Conrad, G. W.

1998-01-01

PURPOSE: Corneas with scars and certain chronic pathologic conditions contain highly sulfated dermatan sulfate, but little is known of the core proteins that carry these atypical glycosaminoglycans. In this study the proteoglycan proteins attached to dermatan sulfate in normal and pathologic human corneas were examined to identify primary genes involved in the pathobiology of corneal scarring. METHODS: Proteoglycans from human corneas with chronic edema, bullous keratopathy, and keratoconus and from normal corneas were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), quantitative immunoblotting, and immunohistology with peptide antibodies to decorin and biglycan. RESULTS: Proteoglycans from pathologic corneas exhibit increased size heterogeneity and binding of the cationic dye alcian blue compared with those in normal corneas. Decorin and biglycan extracted from normal and diseased corneas exhibited similar molecular size distribution patterns. In approximately half of the pathologic corneas, the level of biglycan was elevated an average of seven times above normal, and decorin was elevated approximately three times above normal. The increases were associated with highly charged molecular forms of decorin and biglycan, indicating modification of the proteins with dermatan sulfate chains of increased sulfation. Immunostaining of corneal sections showed an abnormal stromal localization of biglycan in pathologic corneas. CONCLUSIONS: The increased dermatan sulfate associated with chronic corneal pathologic conditions results from stromal accumulation of decorin and particularly of biglycan in the affected corneas. These proteins bear dermatan sulfate chains with increased sulfation compared with normal stromal proteoglycans.

[Vibrio vulnificus infection outside of the fish ponds in northern Israel: acquisition in the "Einot Tzukim" springs near the Dead Sea].

PubMed

Schlesinger, Yechiel; Ben-Shalom, Efrat; Raveh, David P; Yinnon, Amos M; Miskin, Hagit; Rudensky, Bernard

2009-11-01

Vibrio vulnificus is a Gram-negative bacterium that may cause severe skin and systemic infection after exposure of open wounds to contaminated water, especially in patients with underlying disease such as immune-deficiency, iron overload or end stage liver or renal disease. The V. vulnificus infection has been reported in Israel almost exclusively after exposure to Tilapia fish cultivated in fresh water fish ponds in northern Israel. The authors report the first case of V. vulnificus infection acquired in a nature reserve in southeastern Israel, with no connection to fish handling. A 14.5-years-old girl with transfusion-dependant thalassemia major presented with high fever and a rapidly progressive bullous cellulitis of the ankle. The infection occurred around a cut on the left lateral malleolus, after bathing in the fresh water ponds of Einot Tzukim (Ein Feshcha) in south-eastern Israel, and progressed despite the use of broad-spectrum antibiotics. Blood and wound cultures eventually yielded Vibrio vulnificus and appropriate treatment was commenced. The fever subsided after a few days but resolution of the local findings was very gradual and lasted for weeks. The presence of V. vulnificus in natural springs far from the northern artificial fish ponds broadens the danger of this infection. We find it prudent to advise people at risk for V. vulnificus infection, such as those suffering from immunedeficiency, iron overload and end stage liver or renal disease, to refrain from bathing in natural ponds whilst injured.

Bacterial diseases of the skin.

PubMed

Edlich, Richard F; Winters, Kathryne L; Britt, L D; Long, William B

2005-01-01

When considering common bacterial diseases of the skin, rather distinct clinical responses to a variety of bacterial infections have been identified. In these cases, it is the specific site of infection and the attendant inflammatory responses that provide the characteristic clinical picture. When the pyoderma extends just below the stratum corneum, it is called impetigo. Nonbullous impetigo is the most common pediatric skin infection. It usually starts in a traumatized area. The typical lesion begins as an erythematous papule, after which it becomes a unilocular vesicle. When the subcorneal vesicle becomes pustular, it ruptures and eventually becomes a yellow, golden crust that is a hallmark of the disease process. Bullous impetigo is a less common form of impetigo, accounting for fewer than 30% of all impetigo cases. It occurs in infants and is characterized by rapid progression of vesicles to the formation of bullae measuring larger than 5 mm in diameter in previously untraumatized skin. Treatment of nonbullous impetigo must include intervention against the pathogen as well as improvements in the hygiene and living conditions of the patient. A fundamental tenet is to debride the crust (scab) from the wound surface using poloxamer 188. If the lesions are not widespread, topical mupirocin is the treatment of choice. Treatment of bullous impetigo is similar, except that the local cleansing and topical antibiotic must be complemented by systemic antibiotics if there is evidence of disseminating infections. Ecthyma is usually a consequence of failure to treat effectively impetigo. The untreated infection extends deep into the tissue in shallow ulcerations that often heal without scar. Treatment for ecthyma usually requires systemic antibiotics against either staphylococcus or streptococcus. Folliculitis is a pyoderma located within a hair follicle, secondary to follicular occlusion by keratin, overhydration, or either bacterial or fungal infection. Folliculitis may be divided into either a deep or a superficial type. In the superficial type, the pustule is located at the opening of the hair follicle. In the deep form, the infection may extend beyond the confines of the hair follicle, becoming a furuncle or boil. Carbuncles are aggregates of interconnected furuncles that drain through multiple openings of the skin. Treatment of folliculitis must include searching for and avoiding any factors predisposing to infection. If topical antibiotic therapy is ineffective in controlling the infection, surgical drainage of the infected skin abscess will be necessary. Paronychia is the most common bacterial infection of the hand, which often requires surgical incisional drainage. Similarly, a felon that is an infection of the distal pulp of a finger usually requires surgical drainage. Finally, cellulitis is an acute inflammatory reaction involving the skin and underlying subcutaneous tissue. It usually starts as erysipelas and may advance to lymphangitis, lymphadenitis, or gangrene,which will respond to life-saving interventions in the hospital that usually include systemic antibiotic treatment as well as surgical intervention.

Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune diseases in Denmark 1989-2008.

PubMed

Frisch, Morten; Nielsen, Nete Munk; Pedersen, Bo Vestergaard

2014-01-01

Autoimmune diseases have been little studied in gay men and lesbians. We followed 4.4 million Danes, including 9,615 same-sex married (SSM) persons, for 47 autoimmune diseases in the National Patient Registry between 1989 and 2008. Poisson regression analyses provided first hospitalization rate ratios (RRs) comparing rates between SSM individuals and persons in other marital status categories. SSM individuals experienced no unusual overall risk of autoimmune diseases. However, the risk of autoimmune thyroid dysfunction was increased, notably Hashimoto's thyroiditis (women(SSM), RR = 2.92; 95% confidence interval (CI) 1.74-4.55) and Graves' disease (men(SSM), RR = 1.88; 95% CI 1.08-3.01). There was also an excess of primary biliary cirrhosis (women(SSM), RR = 4.09; 95% CI 1.01-10.7), and of psoriasis (men(SSM), RR = 2.48; 95% CI 1.77-3.36), rheumatic fever (men(SSM), RR = 7.55; 95% CI 1.87-19.8), myasthenia gravis (men(SSM), RR = 5.51; 95% CI 1.36-14.4), localized scleroderma (men(SSM), RR = 7.16; 95% CI 1.18-22.6) and pemphigoid (men(SSM), RR = 6.56; 95% CI 1.08-20.6), while Dupuytren's contracture was reduced (men(SSM), RR = 0.64; 95% CI 0.39-0.99). The excess of psoriasis was restricted to same-sex married men with HIV/AIDS (men(SSM), RR = 10.5; 95% CI 6.44-15.9), whereas Graves' disease occurred in excess only among same-sex married men without HIV/AIDS (men(SSM), RR = 1.99; 95% CI 1.12-3.22). Lesbians and immunologically competent gay men in same-sex marriage face no unusual overall risk of autoimmune diseases. However, the observed increased risk of thyroid dysfunction in these lesbians and gay men deserves further study.

Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris.

PubMed

Behzad, M; Möbs, C; Kneisel, A; Möller, M; Hoyer, J; Hertl, M; Eming, R

2012-04-01

Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs). To investigate the long-term efficacy of IA in combination with Rtx in patients with difficult-to-treat PV, we assessed the clinical response to treatment by monitoring the Autoimmune Bullous Skin Disorder Intensity Score, IgG auto-Abs against desmoglein 1 and 3 (Dsg1 and Dsg3) and the dose of systemic CS. We retrospectively analysed clinical and serological parameters of 10 patients with difficult-to-treat PV who received IA at 4-week intervals, followed by Rtx either twice at 1000 mg or four times at 375mg m(-2) . During a 12-month follow-up period, CS were tapered according to the individual clinical status. Six months after the first IA treatment eight of 10 patients were in complete remission on therapy while one patient showed a partial response and one patient was unresponsive to the treatment. At 12 months, six of eight patients were in complete remission on therapy, one patient showed stable disease and one patient had relapsed. Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity and systemic CS were tapered gradually. The present findings show that the combination of IA and Rtx induces rapid clinical remission and long-term control in difficult-to-treat pemphigus. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Neutrophil Collagenase, Gelatinase and Myeloperoxidase in Tears of Stevens-Johnson Syndrome and Ocular Cicatricial Pemphigoid Patients

PubMed Central

Arafat, Samer N.; Suelves, Ana M.; Spurr-Michaud, Sandra; Chodosh, James; Foster, C. Stephen; Dohlman, Claes H.; Gipson, Ilene K.

2013-01-01

Objective To investigate the levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in tears of patients with Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). Design Prospective non-interventional cohort study. Participants Four SJS patients (7 eyes), 19 OCP patients (37 eyes) and 20 post-phacoemulsification healthy controls (40 eyes). Methods Tear washes were collected from all patients and were analyzed for levels of MMP-2, -3, -7, -8, -9, -12, MPO and TIMP-1 using multi-analyte bead-based enzyme-linked immunosorbent assays (ELISA). Total MMP activity was determined using a fluorimetric assay. Correlation studies were performed between the various analytes within study groups. Main Outcome Measures Levels of MMP-2, -3, -7, -8, -9, -12, MPO and TIMP-1 (in ng/µg protein), total MMP activity (in relative fluorescent units/min/µg protein) in tears, MMP-8/TIMP-1, MMP-9/TIMP-1 ratios and the correlations between MMP-8 and MMP-9 and each MMP and MPO. Results MMP-8, MMP-9 and MPO levels were significantly elevated in SJS and OCP tears (SJS > OCP) when compared to controls. MMP activity was highest in SJS while OCP and controls showed lower and similar activities. TIMP-1 levels were decreased in SJS and OCP when compared to controls with OCP levels reaching significance. MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios were markedly elevated in SJS and OCP tears (SJS > OCP) when compared to controls. Across all study groups, MMP-9 levels correlated strongly with MMP-8 and MPO levels and MMP-8 correlated with MPO but did not reach significance in SJS. There was no relationship between MMP-7 and MPO. Conclusions Since MMP-8 and MPO are produced by inflammatory cells, particularly neutrophils, the correlation data indicate that they may be the common source of elevated enzymes including MMP-9 in SJS and OCP tears. Elevated MMP/TIMP ratios and MMP activity suggest an imbalance in tear MMP regulation that may explain the predisposition of these patients to develop corneal melting and chronic complications associated with persistent inflammation. MPO in tears may be a sensitive and specific marker for the quantification of ocular inflammation. PMID:23962653

Quantitative Fundus Autofluorescence in Best Vitelliform Macular Dystrophy: RPE Lipofuscin is not Increased in Non-Lesion Areas of Retina

PubMed Central

Duncker, Tobias; Woods, Russell; Delori, François C.

2018-01-01

Since the lipofuscin of retinal pigment epithelial (RPE) cells has been implicated in the pathogenesis of Best vitelliform macular dystrophy, we quantified fundus autofluorescence (quantitative fundus autofluorescence, qAF) as an indirect measure of RPE lipofuscin levels. Mean non-lesion qAF was found to be within normal limits for age. By spectral domain optical coherence tomography (SD-OCT) vitelliform lesions presented as fluid-filled subretinal detachments containing reflective material. We discuss photoreceptor outer segment debris as the source of the intense fluorescence of these lesions and loss of anion channel functioning as an explanation for the bullous photoreceptor-RPE detachment. Unexplained is the propensity of the disease for central retina. PMID:26427423

Quantitative Fundus Autofluorescence in Best Vitelliform Macular Dystrophy: RPE Lipofuscin is not Increased in Non-Lesion Areas of Retina.

PubMed

Sparrow, Janet R; Duncker, Tobias; Woods, Russell; Delori, François C

2016-01-01

Since the lipofuscin of retinal pigment epithelial (RPE) cells has been implicated in the pathogenesis of Best vitelliform macular dystrophy, we quantified fundus autofluorescence (quantitative fundus autofluorescence, qAF) as an indirect measure of RPE lipofuscin levels. Mean non-lesion qAF was found to be within normal limits for age. By spectral domain optical coherence tomography (SD-OCT) vitelliform lesions presented as fluid-filled subretinal detachments containing reflective material. We discuss photoreceptor outer segment debris as the source of the intense fluorescence of these lesions and loss of anion channel functioning as an explanation for the bullous photoreceptor-RPE detachment. Unexplained is the propensity of the disease for central retina.

[Corneal lesions in Kindler syndrome: a case report].

PubMed

Chéour, M; Mazlout, H; Ben Jalel, W; Brour, J; Baroudi, B; Kraiem, A

2012-01-01

Kindler syndrome is a rare autosomal recessive genodermatosis belonging to the class of bullous poikiloderma. Corneal lesions are rare. We report a case of ocular lesions in this syndrome. We report the case of a 57-year-old patient followed since childhood in dermatology with the diagnosis of Kindler syndrome. He presented to the ophthalmology department with decreased vision. Ophthalmologic examination showed symblepharon, ectropion in both eyes, and corneal deformation. The role played by the abnormal protein in epithelial integrity suggests that ocular and more particularly corneal involvement is not rare in Kindler syndrome. In fact, it is less known by ophthalmologists and dermatologists are not aware of the ophthalmologic manifestations. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Microwave-superheated Vics Vapo Rub: an ocular public health danger.

PubMed

Fung, Anne E; Oxford, Karen W

2004-02-01

To report a case of a microwave-oven superheated petroleum-based liquid causing severe chemical and thermal ocular burns treated successfully with amniotic membrane transplantation. Observational case report. Retrospective review of clinical case. A 77-year-old woman sustained a severe combined chemical and thermal burn from microwave-heated Vicks Vapo-Rub requiring amniotic membrane transplant, with subsequent development of phacomorphic glaucoma, requiring cataract extraction, and bullous keratopathy, requiring penetrating keratoplasty. As microwave oven use becomes more commonplace, the risk of superheating liquids becomes an increasingly significant ocular danger. Continued efforts to educate the public about safe microwave use is necessary. Additionally, amniotic membrane transplantation was found to be effective in managing a combined chemical and thermal ocular burn.

Incidental lung volume reduction following fulminant pulmonary hemorrhage in a patient with severe emphysema.

PubMed

Hetzel, Juergen; Spengler, Werner; Horger, Marius; Boeckeler, Michael

2015-06-01

Endoscopic lung volume reduction is an emerging technique meant to improve lung function parameters, quality of life, and exercise tolerance in patients with severe lung emphysema. This is the first report of lung volume reduction by autologous blood in a patient with non-bullous lung emphysema. A 74-year-old woman with heterogeneous lung emphysema developed accidentally diffuse lobar bleeding immediately after valve placement. Due to persistent hemorrhage, the valves had to be removed shortly thereafter. Despite extraction of the valves, respiratory function of the patient improved rapidly indicated also by a drop in the COPD assessment test questionnaire, 3 months later. This was consistent with both improvement of lung function tests and six-minute walking test.

Challenging Airway Secondary to Purpura Fulminans With Face and Neck Bullae in a Premature Infant: A Case Report.

PubMed

Ekeoduru, Rhashedah A; Greives, Matthew R; Nesrsta, Eric A

2017-02-15

A former 25-week-old neonate presented at 34 weeks postconceptual age with necrotizing fasciitis and purpura fulminans because of Group B Streptococcus infection. He was septic and coagulopathic when he was intubated, and the endotracheal tube was secured with adhesives. When he subsequently developed large purpuric, bullous lesions on the face and neck, he presented to the operating room for excision and debridement of his facial lesions. No change was made in how the endotracheal tube was secured. Midprocedure, an unintentional extubation occurred. We describe how we subsequently secured the airway and make recommendations on how to avoid this problem in the future and for rescue preparation before the procedure.

Advanced therapies of skin injuries.

PubMed

Maver, Tina; Maver, Uroš; Kleinschek, Karin Stana; Raščan, Irena Mlinarič; Smrke, Dragica Maja

2015-12-01

The loss of tissue is still one of the most challenging problems in healthcare. Efficient laboratory expansion of skin tissue to reproduce the skins barrier function can make the difference between life and death for patients with extensive full-thickness burns, chronic wounds, or genetic disorders such as bullous conditions. This engineering has been initiated based on the acute need in the 1980s and today, tissue-engineered skin is the reality. The human skin equivalents are available not only as models for permeation and toxicity screening, but are frequently applied in vivo as clinical skin substitutes. This review aims to introduce the most important recent development in the extensive field of tissue engineering and to describe already approved, commercially available skin substitutes in clinical use.

Epidermolysis bullosa acquisita: clinical manifestations, microscopic findings, and surgical periodontal therapy. A case report.

PubMed

Hakki, S S; Celenligil-Nazliel, H; Karaduman, A; Usubütün, A; Ertoy, D; Ayhan, A; Ruacan, S

2001-04-01

Epidermolysis bullosa acquisita (EBA) is an uncommon, acquired, chronic subepidermal bullous disease. This report describes a case of EBA with gingival involvement. A 43-year-old woman with EBA was referred to our clinic for periodontal therapy because of gingival tenderness and bleeding. She has been on cyclosporin A therapy for the last 2 years. Clinical findings were analyzed. Anterior gingivectomy operations were performed in 2 stages. The samples obtained during the surgery were examined using histopathologic, immunohistologic, and electronmicroscopic methods. Long-term effects of the surgical periodontal treatment on gingiva were evaluated both clinically and microscopically. The dentition displayed minimal enamel hypoplasia. Decayed, missing, and filled surfaces score was found to be elevated. Periodontal examination showed generalized diffuse gingival inflammation and gingival enlargement localized mainly to the anterior region. Nikolsky's sign was positive. However, wound healing was uneventful after the operations. Microscopic findings were similar to those obtained from the skin. Twenty-one months after the operations, Nikolsky's sign was negative and no remarkable gingival inflammation was noted. Microscopic examination revealed that the blisters were fewer in number and smaller in size. These results indicate that gingival tissues may also be involved in EBA. Uneventful wound healing after periodontal surgery in this case suggests that periodontal surgery can be performed in patients with EBA. Moreover, both our clinical and histopathologic findings imply that gingivectomy proves useful in maintaining gingival integrity in these patients. Our data may also suggest that the patients with EBA are highly likely to develop dental caries.

Genome-wide gene expression profiling reveals unsuspected molecular alterations in pemphigus foliaceus

PubMed Central

Malheiros, Danielle; Panepucci, Rodrigo A; Roselino, Ana M; Araújo, Amélia G; Zago, Marco A; Petzl-Erler, Maria Luiza

2014-01-01

Pemphigus foliaceus (PF) is a complex autoimmune disease characterized by bullous skin lesions and the presence of antibodies against desmoglein 1. In this study we sought to contribute to a better understanding of the molecular processes in endemic PF, as the identification of factors that participate in the pathogenesis is a prerequisite for understanding its biological basis and may lead to novel therapeutic interventions. CD4+ T lymphocytes are central to the development of the disease. Therefore, we compared genome-wide gene expression profiles of peripheral CD4+ T cells of various PF patient subgroups with each other and with that of healthy individuals. The patient sample was subdivided into three groups: untreated patients with the generalized form of the disease, patients submitted to immunosuppressive treatment, and patients with the localized form of the disease. Comparisons between different subgroups resulted in 135, 54 and 64 genes differentially expressed. These genes are mainly related to lymphocyte adhesion and migration, apoptosis, cellular proliferation, cytotoxicity and antigen presentation. Several of these genes were differentially expressed when comparing lesional and uninvolved skin from the same patient. The chromosomal regions 19q13 and 12p13 concentrate differentially expressed genes and are candidate regions for PF susceptibility genes and disease markers. Our results reveal genes involved in disease severity, potential therapeutic targets and previously unsuspected processes involved in the pathogenesis. Besides, this study adds original information that will contribute to the understanding of PF's pathogenesis and of the still poorly defined in vivo functions of most of these genes. PMID:24813052

Experimental Genital Infection of Male Guinea Pigs with the Agent of Guinea Pig Inclusion Conjunctivitis and Transmission to Females

PubMed Central

Mount, David T.; Bigazzi, Pierluigi E.; Barron, Almen L.

1973-01-01

Male guinea pigs were inoculated intraurethrally with the agent of guinea pig inclusion conjunctivitis (Gp-ic). Cytoplasmic inclusions were found in superficial epithelial cells of the urethra in smears and stained sections. Gp-ic antigen(s) was detected by immunofluorescent staining of sections. There was no marked urethral exudate, but many animals developed bullous lesions on the glans and the body of the penis and a severe inflammatory lesion of the hind leg. All males demonstrated an antibody response and most of them showed a positive skin test reaction. Venereal transmission to females of Gp-ic infection was shown to occur as determined by detection of inclusions in vaginal smears, antibody response, and positive skin tests. Images PMID:4594119

Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy

PubMed Central

Ahadome, Sarah D.; Mathew, Rose; Reyes, Nancy J.; Mettu, Priyatham S.; Cousins, Scott W.; Calder, Virginia L.; Saban, Daniel R.

2016-01-01

Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads to blindness in trachoma, pemphigoid, and allergy. The indirect fibrogenic role of DCs via T cell activation and inflammatory cell recruitment is well documented. However, here we demonstrate that DCs can directly induce fibrosis. In the mouse model of allergic eye disease (AED), classical CD11b+ DCs in the ocular mucosa showed increased activity of aldehyde dehydrogenase (ALDH), the enzyme required for retinoic acid synthesis. In vitro, CD11b+ DC–derived ALDH was associated with 9-cis-retinoic acid ligation to retinoid x receptor (RXR), which induced conjunctival fibroblast activation. In vivo, stimulating RXR led to rapid onset of ocular mucosal fibrosis, whereas inhibiting ALDH activity in DCs or selectively depleting DCs markedly reduced fibrosis. Collectively, these data reveal a profibrotic ALDH-dependent pathway by DCs and uncover a role for DC retinoid metabolism. PMID:27595139

Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring

PubMed Central

Ahadome, Sarah D.; Abraham, David J.; Rayapureddi, Suryanarayana; Saw, Valerie P.; Saban, Daniel R.; Calder, Virginia L.; Norman, Jill T.; Ponticos, Markella; Daniels, Julie T.; Dart, John K.

2016-01-01

Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. Aldehyde dehydrogenase family 1 (ALDH1) is upregulated in both ocular MMP (OMMP) conjunctiva and cultured fibroblasts. Application of the ALDH metabolite, retinoic acid (RA), to normal human conjunctival fibroblasts in vitro induced a diseased phenotype. Conversely, application of ALDH inhibitors, including disulfiram, to OMMP fibroblasts in vitro restored their functionality to that of normal controls. ALDH1 is also upregulated in the mucosa of the mouse model of scarring allergic eye disease (AED), used here as a surrogate for OMMP, in which topical application of disulfiram decreased fibrosis in vivo. These data suggest that progressive scarring in OMMP results from ALDH/RA fibroblast autoregulation, that the ALDH1 subfamily has a central role in immune-mediated ocular mucosal scarring, and that ALDH inhibition with disulfiram is a potential and readily translatable antifibrotic therapy. PMID:27699226

[Case report of osteo-odonto keratoprosthesis (Strampelli) and of Dacron keratoprosthesis (Pintucci)].

PubMed

Chammartin, M; Goldblum, D; Früh, B; Wilkens, L; Bosshardt, D; Sarra, G-M

2009-03-01

In severe forms of ocular surface disorders keratoprostheses provide the ultimate possibility to restore vision. They are made of an optical cylinder integrated with a supporting biocompatible or biological haptic. We report on two patients with different types of keratoprostheses. An 88-year-old woman with ocular pemphigoid received in 1970 a bilateral osteo-odonto-keratoprosthesis (Strampelli). A 59-year-old man with refractory corneal ulcer after corneal grafting received in 2003 a keratoprosthesis with supporting Dacron tissue (Pintucci). The course 35 years after implantation of the osteo-odonto-keratoprosthesis was uneventful. Histologically there were no signs of loosening, rejection or infection. The autologous dentin, which was used for the fixation, was still present. The eye with the Dacron fixated prosthesis (Pintucci) had to be enucleated due to a loosening with endophthalmitis one and a half year after implantation. Keratoprostheses with autologous fixation often show good long-term results. On the other hand, prostheses with synthetic material are more often complicated by dislocation and inflammation.

Immune-mediated diseases: what can be found in the oral cavity?

PubMed

Bascones-Martínez, Antonio; García-García, Virginia; Meurman, Jukka H; Requena-Caballero, Luis

2015-03-01

Immune-mediated diseases frequently affect oral mucosa, which may often be the first site of clinical manifestation. In this review, we describe the most important oral lesions related to inflammatory disorders and present their management and novel therapies. The review is based on an open PubMed literature search from 1980 to 2012 with relevant keywords. Pemphigus vulgaris, oral lichen planus, cicatricial pemphigoid, erythema multiforme, Stevens-Johnson syndrome, systemic lupus erythematosus, Sjögren's syndrome, and linear IgA dermatosis are the immune-mediated diseases with oral manifestations discussed. Etiology is unknown in most of these diseases, but recently some of them have been found to share common genes. Modern treatment of these diseases is based on drugs that interfere along the pathogenic mechanisms instead of the still commonly used palliative measures. However, the immunomodulatory drugs may also cause oral side effects, complicating the clinical picture. Therefore, consulting dental or oral medicine specialists can be necessary in some cases with various immune-mediated diseases. © 2014 The International Society of Dermatology.

Neutrophil collagenase, gelatinase, and myeloperoxidase in tears of patients with stevens-johnson syndrome and ocular cicatricial pemphigoid.

PubMed

Arafat, Samer N; Suelves, Ana M; Spurr-Michaud, Sandra; Chodosh, James; Foster, C Stephen; Dohlman, Claes H; Gipson, Ilene K

2014-01-01

To investigate the levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in tears of patients with Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). Prospective, noninterventional cohort study. Four SJS patients (7 eyes), 19 OCP patients (37 eyes), and 20 healthy controls who underwent phacoemulsification (40 eyes). Tear washes were collected from all patients and were analyzed for levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 using multianalyte bead-based enzyme-linked immunosorbent assays. Total MMP activity was determined using a fluorometric assay. Correlation studies were performed between the various analytes within study groups. Levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 (in nanograms per microgram of protein) and total MMP activity (in relative fluorescent units per minute per microgram of protein) in tears; MMP-8-to-TIMP-1 ratio; MMP-9-to-TIMP-1 ratio; and the correlations between MMP-8 and MMP-9 and both MMP and MPO. MMP-8, MMP-9, and MPO levels were elevated significantly in SJS and OCP tears (SJS>OCP) when compared with controls. The MMP activity was highest in SJS patients, whereas OCP patients and controls showed lower and similar activities. The TIMP-1 levels were decreased in SJS and OCP patients when compared with those in controls, with levels in OCP patients reaching significance. The MMP-8-to-TIMP-1 and MMP-9-to-TIMP-1 ratios were markedly elevated in SJS and OCP tears (SJS>OCP) when compared with those of controls. Across all study groups, MMP-9 levels correlated strongly with MMP-8 and MPO levels, and MMP-8 correlated with MPO, but it did not reach significance in SJS patients. There was no relationship between MMP-7 and MPO. Because MMP-8 and MPO are produced by inflammatory cells, particularly neutrophils, the correlation data indicate that they may be the common source of elevated enzymes, including MMP-9, in SJS and OCP tears. Elevated MMP-to-TIMP ratios and MMP activity suggest an imbalance in tear MMP regulation that may explain the predisposition of these patients to demonstrate corneal melting and chronic complications associated with persistent inflammation. Myeloperoxidase in tears may be a sensitive and specific marker for the quantification of ocular inflammation. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Fatal Vibrio parahemolyticus septicemia in a patient with cirrhosis. A case report and review of the literature.

PubMed

Hally, R J; Rubin, R A; Fraimow, H S; Hoffman-Terry, M L

1995-06-01

Vibrio parahemolyticus has been well documented to cause outbreaks of infectious diarrhea, usually related to poor food handling; only rarely has it been reported to cause fetal septicemia. In contrast, Vibrio vulnificus is a well-known cause of septicemia, especially in patients with cirrhosis. A 31-year-old woman with cirrhosis who developed fatal V. parahemolyticus sepsis after ingesting raw seafood is described. We review the clinical syndromes associated with sepsis caused by these two organisms. Leg pain and bullous skin lesions may be a clue to the diagnosis. Febrile patients with cirrhosis should be questioned regarding recent seafood ingestion, and appropriate antibiotics chosen if this history is obtained. Physicians should inform patients at risk to avoid raw seafood in an attempt to prevent this potentially lethal syndrome.

Treatments for Severe Cutaneous Adverse Reactions

PubMed Central

Cho, Yung-Tsu

2017-01-01

Severe cutaneous adverse reaction (SCAR) is life-threatening. It consists of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed drug eruptions (GBFDE). In the past years, emerging studies have provided better understandings regarding the pathogenesis of these diseases. These diseases have unique presentations and distinct pathomechanisms. Therefore, theoretically, the options of treatments might be different among various SCARs. However, due to the rarity of these diseases, sufficient evidence is still lacking to support the best choice of treatment for patients with SCAR. Herein, we will provide a concise review with an emphasis on the characteristics and treatments of each SCAR. It may serve as a guidance based on the current best of knowledge and may shed light on the directions for further investigations. PMID:29445753

Emerging treatment options for the management of pemphigus vulgaris

PubMed Central

Kridin, Khalaf

2018-01-01

Pemphigus vulgaris (PV) is a life-threatening disease belonging to the pemphigus group of autoimmune intra-epidermal bullous diseases of the skin and mucosae. The therapeutic management of PV remains challenging and, in some cases, conventional therapy is not adequate to induce clinical remission. The cornerstone of PV treatment remains systemic corticosteroids. Although very effective, long-term corticosteroid administration is characterized by substantial adverse effects. Corticosteroid-sparing adjuvant therapies have been employed in the treatment of PV, aiming to reduce the necessary cumulative dose of corticosteroids. Specifically, immunosuppressive agents such as azathioprine and mycophenolate mofetil are widely used in PV. More recently, high-dose intravenous immunoglobulins, immunoadsorption, and rituximab have been established as additional successful therapeutic options. This review covers both conventional and emerging therapies in PV. In addition, it sheds light on potential future treatment strategies for this disease. PMID:29740210

Safety and potential efficacy of gemfibrozil as a supportive treatment for children with late infantile neuronal ceroid lipofuscinosis and other lipid storage disorders.

PubMed

Kim, Kyeongsoon; Kleinman, Hynda K; Lee, Hahn-Jun; Pahan, Kalipada

2017-06-17

Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is a group of genetically distinct lysosomal disorders that mainly affect the central nervous system, resulting in progressive motor and cognitive decline primarily in children. Multiple distinct genes involved in the metabolism of lipids have been identified to date with various mutations in this family of diseases. There is no cure for these diseases but some new therapeutic approaches have been tested that offer more hope than the standard palliative care. Many of the therapeutic advances require invasive procedures but some progress in slowing the disease has been found and more options can be expected in the future. We also review the literature on children with disease/conditions other than NCL for the non-invasive use, safety, and tolerability of a lipid-lowering drug, gemfibrozil, as a potential treatment for NCLs. Gemfibrozil has shown efficacy in an animal model of NCL known as CLN2 (late infantile classic juvenile) and has been shown to be safe for lowering lipids in children. Among the 200 non-NCL children found in the published literature who were treated with gemfibrozil for NCL-related problems, only 3 experienced adverse events, including 2 with muscle pain and 1 with localized linear IgA bullous dermatitis. We conclude that gemfibrozil is safe for long-term use in children, causes minimal adverse events, is well tolerated, and may delay the progression of NCLs. Gemfibrozil may potentially be an alternative to more invasive therapeutic approaches currently under investigation and has the potential to be used in combination with other therapeutic approaches.

Hospital admissions for vitamin D related conditions and subsequent immune-mediated disease: record-linkage studies

PubMed Central

2013-01-01

Background Previous studies have suggested that there may be an association between vitamin D deficiency and the risk of developing immune-mediated diseases. Methods We analyzed a database of linked statistical records of hospital admissions and death registrations for the whole of England (from 1999 to 2011). Rate ratios for immune-mediated disease were determined, comparing vitamin D deficient cohorts (individuals admitted for vitamin D deficiency or markers of vitamin D deficiency) with comparison cohorts. Results After hospital admission for either vitamin D deficiency, osteomalacia or rickets, there were significantly elevated rates of Addison’s disease, ankylosing spondylitis, autoimmune hemolytic anemia, chronic active hepatitis, celiac disease, Crohn’s disease, diabetes mellitus, pemphigoid, pernicious anemia, primary biliary cirrhosis, rheumatoid arthritis, Sjogren’s syndrome, systemic lupus erythematosus, thyrotoxicosis, and significantly reduced risks for asthma and myxoedema. Conclusions This study shows that patients with vitamin D deficiency may have an increased risk of developing some immune-mediated diseases, although we cannot rule out reverse causality or confounding. Further study of these associations is warranted and these data may aid further public health studies. PMID:23885887

The osteo-odonto-keratoprosthesis (OOKP).

PubMed

Liu, Christopher; Paul, Bobby; Tandon, Radhika; Lee, Edward; Fong, Ken; Mavrikakis, Ioannis; Herold, Jim; Thorp, Simon; Brittain, Paul; Francis, Ian; Ferrett, Colin; Hull, Chris; Lloyd, Andrew; Green, David; Franklin, Valerie; Tighe, Brian; Fukuda, Masahiko; Hamada, Suguru

2005-01-01

The osteo-odonto-keratoprosthesis (OOKP), although described over 40 years ago, remains the keratoprosthesis of choice for end-stage corneal blindness not amenable to penetrating keratoplasty. It is particularly resilient to a hostile environment such as the dry keratinized eye resulting from severe Stevens-Johnson syndrome, ocular cicatricial pemphigoid, trachoma, and chemical injury. Its rigid optical cylinder gives excellent image resolution and quality. The desirable properties of the theoretical ideal keratoprosthesis is described. The indications, contraindications, and patient assessment (eye, tooth, buccal mucosa, psychology) for OOKP surgery are described. The surgical and anaesthetic techniques are described. Follow-up is life-long in order to detect and treat complications, which include oral, oculoplastic, glaucoma, vitreo-retinal complications and extrusion of the device. Resorption of the osteo-odonto-lamina is responsible for extrusion, and this is more pronounced in tooth allografts. Regular imaging with spiral-CT or electron beam tomography can help detect bone and dentine loss. The optical cylinder design is discussed. Preliminary work towards the development of a synthetic OOKP analogue is described. Finally, we describe how to set up an OOKP national referral center.

Linear IgA dermatosis associated with ulcerative colitis: complete and sustained remission after total colectomy.

PubMed

Vargas, Thiago Jeunon de Sousa; Fialho, Mônica; Santos, Luiza Tavares dos; Rodrigues, Palmira Assis de Jesus Barreto; Vargas, Ana Luisa Bittencourt Sampaio Jeunon; Sousa, Maria Auxiliadora Jeunon

2013-01-01

Linear IgA dermatosis has been increasingly associated with inflammatory bowel diseases, particularly ulcerative colitis. A 13-year-old male patient with an 11-month history of ulcerative colitis developed vesicles, pustules and erosions on the skin of the face, trunk and buttocks and in the oral mucosa. The work-up revealed a neutrophil-rich sub-epidermal bullous disease and linear deposition of IgA along the dermoepidermal junction, establishing the diagnosis of linear IgA dermatosis. The patient experienced unsatisfactory partial control of skin and intestinal symptoms despite the use of adalimumab, mesalazine, prednisone and dapsone for some months. After total colectomy, he presented complete remission of skin lesions, with no need of medications during two years of follow-up. A review of previously reported cases of the association is provided here and the role of ulcerative colitis in triggering linear IgA dermatosis is discussed.

Granular C3 Dermatosis.

PubMed

Hashimoto, Takashi; Tsuruta, Daisuke; Yasukochi, Atsushi; Imanishi, Hisayoshi; Sekine, Hideharu; Fujita, Teizo; Wanibuchi, Hideki; Gi, Min; Kárpáti, Sarolta; Sitaru, Cassian; Zone, John J; Endo, Daisuke; Abe, Shinichi; Nishino, Tomoya; Koji, Takehiko; Ishii, Norito

2016-08-23

There has been no previous systematic study of bullous skin diseases with granular basement membrane zone deposition exclusively of C3. In this study we collected 20 such patients, none of whom showed cutaneous vasculitis histopathologically. Oral dapsone and topical steroids were effective. Various serological tests detected no autoantibodies or autoantigens. Direct immunofluorescence for various complement components revealed deposition only of C3 and C5-C9, indicating that no known complement pathways were involved. Studies of in situ hybridization and micro-dissection with quantitative RT-PCR revealed a slight reduction in expression of C3 in patient epidermis. These patients may represent a new disease entity, for which we propose the term "granular C3 dermatosis". The mechanism for granular C3 deposition in these patients is unknown, but it is possible that the condition is caused by autoantibodies to skin or aberrant C3 expression in epidermal keratinocytes.

Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delattre, J.Y.; Safai, B.; Posner, J.B.

1988-02-01

In 15 months we encountered eight patients with intracranial tumors who developed erythema multiforme (EM) or erythema multiforme bullosa (Stevens-Johnson syndrome). All occurred shortly after use of phenytoin (DPH) and brain radiation therapy (WBRT). The clinical picture differed from the classic form of EM in that the erythema began on the scalp and spread to the extremities, progressing in three cases to extensive bullous formation. There were no cases of EM among patients who received either DPH or radiotherapy alone. The combination of DPH, WBRT, and tapering of steroids seems to predispose to EM. The pathogenesis of the disorder ismore » probably immunologic. In the absence of seizures, anticonvulsants should not be given routinely to patients with brain tumors. When anticonvulsants are necessary in patients scheduled for WBRT, DPH may not be the drug of choice.« less

[Lung volume reduction surgery for emphysema and bullous pulmonary emphysema].

PubMed

Le Pimpec-Barthes, F; Das Neves-Pereira, J-C; Cazes, A; Arame, A; Grima, R; Hubsch, J-P; Zukerman, C; Hernigou, A; Badia, A; Bagan, P; Delclaux, C; Dusser, D; Riquet, M

2012-04-01

The improvement of respiratory symptoms for emphysematous patients by surgery is a concept that has evolved over time. Initially used for giant bullae, this surgery was then applied to patients with diffuse microbullous emphysema. The physiological and pathological concepts underlying these surgical procedures are the same in both cases: improve respiratory performance by reducing the high intrapleural pressure. The functional benefit of lung volume reduction surgery (LVRS) in the severe diffuse emphysema has been validated by the National Emphysema Treatment Trial (NETT) and the later studies which allowed to identify prognostic factors. The quality of the clinical, morphological and functional data made it possible to develop recommendations now widely used in current practice. Surgery for giant bullae occurring on little or moderately emphysematous lung is often a simpler approach but also requires specialised support to optimize its results. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Skin: Major target organ of allergic reactions to small molecular weight compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merk, Hans F.; Baron, Jens M.; Neis, Mark M.

2007-11-01

Skin is a major target organ for allergic reactions to small molecular weight compounds. Drug allergic reactions may be life-threatening such as in the case of anaphylactic reactions or bullous drug reactions and occur in about 5% of all hospitalized patients. Allergic contact dermatitis has an enormous influence on the social life of the patient because it is the most frequent reason for occupational skin diseases and the treatment and prevention of this disease cost approximately Euro 3 billion per year in Germany. The different proposed pathophysiological pathways leading to a drug eruption are discussed in this paper. All majormore » enzymes which are involved in the metabolism of xenobiotica were shown to be present in skin. Evidence supporting the role of metabolism in the development of drug allergy and allergic contact dermatitis is demonstrated in the example of sulphonamides and fragrances.« less

[Drug eruptions caused by noncorticoid anti-inflammatory agents].

PubMed

Roujeau, J C; Guillaume, J C; Revuz, J; Touraine, R

1984-01-01

Non-steroidal anti-inflammatory drugs (NSAI) may elicit various kinds of cutaneous side effects. The commonest ones are non-specific erythematous eruptions, sometimes with a phototoxic distribution, and urticaria. Vasculitis and severe bullous eruptions (Stevens-Johnson's syndrome and Toxic Epidermal Necrolysis) are rare but may have severe outcomes. The overall incidence of cutaneous reactions is about the same for all NSAI, 1 to 3 p. 100, during the clinical studies performed before marketing the drug, but this increases afterwards (up to 45 p. 100 for Benoxaprofen). Drugs with long half-lives may carry a higher risk for severe cutaneous reactions. NSAI are now the main cause of drug induced TEN. Urticarial reactions seem related to pharmacological phenomena while the pathogenic events leading to other kinds of skin reactions remain unknown. An hypersensitivity reaction is postulated. The therapeutic value of corticosteroids for the severe cutaneous side effects of drugs is still controversial.

Oral and topical sodium cromoglicate in the treatment of diffuse cutaneous mastocytosis in an infant

PubMed Central

Edwards, Alan Martin; Čapková, Štěpánka

2011-01-01

Diffuse cutaneous mastocytosis (DCM) is a rare, severe, variant of cutaneous mastocytosis. The authors report the case of a male infant who developed maculae and maculopapulae on his legs and abdomen when aged 3.5 months, which spread to all body surfaces within weeks. Diagnosis of DCM was made at the age of 6 months when he had developed extensive bullous eruptions, generalised pruritus, flushing and abdominal pain. Treatment was started with oral dimethindine maleate. At the age of 18 months, oral sodium cromoglicate (SCG) was introduced. At the age of 23 months, additional treatment was started with a cutaneous emulsion containing 4% SCG. Continued treatment with oral dimethindine maleate, oral SCG with the dose maintained at 25 mg/kg/day, and SCG 4% cutaneous emulsion applied two to four times daily has resulted in a steady improvement of symptoms and skin appearance. PMID:22693187

Coma blisters in children: case report and review of the literature.

PubMed

Bosco, Laura; Schena, Donatella; Colato, Chiara; Biban, Paolo; Girolomoni, Giampiero

2013-12-01

Coma-induced blisters is a rare condition associated with prolonged impairment of conscious level, which is relatively well-known in adults following overdose with barbiturates. However, it has been very rarely described in children. A case of coma-bullae occurring in an 11-year-old child with meningoencephalitis is herein reported. The bullous lesions occurred on the limbs and trunks, and evolved into necrotic ulcers in a few days. No correlation with any drug overdosage was found. A skin biopsy revealed epidermal and eccrine sweat gland necrosis with abundant neutrophils, and thrombosis of the vessels in the lower dermis. A comprehensive review of the literature showed that only 5 cases of coma-bullae in children have been published so far. Coma blistering resolves spontaneously within days or weeks. Diagnosis of coma-bullae may require careful clinical-pathologic correlation to exclude other blistering diseases in children.

Bilateral rhegmatogenous retinal detachment due to unusual retinal degeneration in Down syndrome: A case report.

PubMed

Yonemoto, Yumiko; Morishita, Seita; Fukumoto, Masanori; Mimura, Masashi; Sato, Takaki; Kida, Teruyo; Kojima, Shota; Oku, Hidehiro; Sugasawa, Jun; Ikeda, Tsunehiko

2018-06-01

The aim of this study was to report a case of Down syndrome (DS) complicated with bilateral retinal detachment (RD) due to unusual retinal degeneration. A 9-year-old girl complained of bilateral visual disturbance during a follow-up examination for myopia and strabismus. Slit-lamp examination revealed moderate posterior subcapsular cataract in both eyes. B-mode echography showed bilateral bullous RD; however, it was difficult to detect the causal retinal breaks due to poor mydriasis. For treatment, the patient underwent bilateral lensectomy, vitrectomy, and silicone oil tamponade. Intraoperative findings revealed symmetrical retinal breaks and unusual caterpillar-like retinal degeneration on the upper temporal side of both eyes. Three months later, the patient underwent bilateral silicone oil removal and intraocular lens implantation. In this case, the retinal degeneration was morphologically different from retinal lattice degeneration, thus suggesting that it might be involved in the onset of DS-related bilateral RD.

Adverse drug events in the oral cavity.

PubMed

Yuan, Anna; Woo, Sook-Bin

2015-01-01

Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and the new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. Some examples include osteonecrosis, seen with not only bisphosphonates but also antiangiogenic agents, and the distinctive ulcers caused by mammalian target of rapamycin inhibitors. As newer therapeutic agents are approved, it is likely that more adverse drug events will be encountered. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely, xerostomia, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, white lesions, dysesthesia, osteonecrosis, infection, angioedema, and malignancy. Oral health care providers should be familiar with such events, as they will encounter them in their practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of cannabis smoking on lung function and respiratory symptoms: a structured literature review

PubMed Central

Ribeiro, Luis IG; Ind, Philip W

2016-01-01

As cannabis use increases, physicians need to be familiar with the effects of both cannabis and tobacco on the lungs. However, there have been very few long-term studies of cannabis smoking, mostly due to legality issues and the confounding effects of tobacco. It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC. The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant. Bullous lung disease, barotrauma and cannabis smoking have been recognised in case reports and small series. More work is needed to address the effects of cannabis on lung function, imaging and histological changes. PMID:27763599

Definitive and differential diagnosis of desquamative gingivitis through direct immunofluorescence studies.

PubMed

Suresh, Lakshmanan; Neiders, Mirdza E

2012-10-01

Desquamative gingivitis (DG) is a common clinical manifestation of oral autoimmune vesiculobullous diseases (VBDs). Their polymorphous clinical presentations coupled with similar histologic features make diagnosis indistinguishable among the different VBDs. Direct immunofluorescence (IF) studies are valuable gold-standard diagnostic tests that allow for discrimination among the various VBDs that present with DG. There have been no recent detailed analyses done that have used conventional light microscopy and direct IF in diagnosis to document the clinical associations of DG with various autoimmune oral diseases. The aim of this study is to examine retrospectively a large cohort of patients with DG for associated diseases and to determine the utility of direct IF and conventional light microscopy in establishing a definitive diagnosis. During a 14-month period, our laboratory in Buffalo, New York, received 239 consecutive archival cases of gingival biopsy with a clinical diagnosis of DG. These specimens were submitted to establish or rule out a diagnosis of a direct IF-positive VBD. The demographic, clinical, and microscopic findings were tabulated using established inclusion and diagnostic criteria. Approximately half the number (48.1%) of biopsies received for direct IF studies were submitted by periodontists. Slightly more than half of the patients (53%) previously had biopsies submitted for both hematoxylin and eosin (H & E) and direct IF testing. There was a female predilection for all the diseases studied except for pemphigus and linear immunoglobulin A disease. Oral lichen planus was the most common disease presenting as DG, followed by pemphigoid. The clinical diagnosis of lichen planus correlated with the biopsy findings in 80% of the cases and with pemphigoid in 60%. Definitive diagnosis was rendered to ≈80% of the gingival biopsies submitted. Negative cases of direct IF presenting as DG had significant pathology, such as dysplasia and carcinoma, which would have been otherwise missed if H & E studies had not been performed. This study has the largest cohort of patients with DG suspected of VBD reported in the literature. The patients were predominantly females who had most often been seen by a periodontist. The definitive diagnosis of DG was most accurately achieved when H & E along with two biopsies for direct IF studies were submitted for testing. H & E studies were particularly important for definitive diagnosis of negative cases. Oral lichen planus was the most common disease presenting as DG, which is consistent with recent studies. Systemic connective tissue disorders that present as DG at initial clinical examination require direct IF and serum studies for a conclusive diagnosis. Clinical pathologic correlation, including history, presentation, H & E, and direct IF studies, are essential in establishing a definitive and differential diagnosis for cases presenting with DG.

Corneal graft rejection in African Americans at Howard University Hospital

PubMed Central

Ferdinand, Larry; Ngakeng, Vanessa; Copeland, Robert A.

2011-01-01

Purpose There is scarcity of data in the literature on cornel graft rejection rate in patients exclusively of African ancestry. The purpose of this study was to evaluate the rejection rate of corneal transplant surgery performed at Howard University Hospital on such patients over a 15 year period. Design A retrospective evaluation was performed of the cornea graft rejection and corneal graft failure rate in 125 penetrating keratoplasties (PKPs) done by one corneal specialist at Howard University Hospital from January 1, 1990 to August 31, 2005. Methods Of the 125 patients, 62 were eliminated from the study because of re-grafted eyes, non-African descent, primary graft failures, follow-up less than 1 month and lack of availability of charts. This study, therefore, studied and recorded data from 63 penetrating keratoplasties of 63 eyes from 60 patients. Results Episodes of graft rejection were documented in 23 eyes (36.5% of cases). Nine out of the 23 graft rejections manifested to secondary graft failure (39%). Overall, there were nine out of the 63 PKPs (14.3%) that resulted in secondary graft failure over the past 15 years. The major diagnostic categories were bullous keratopathy 24 (38%), keratoconus 10 (15.8%), Fuch’s dystrophy 4 (6.3%), other 20 (31.7%). Of the cases with episodes of rejection and failure, 4.3% and none were attributable to keratoconus, 30.4% and 22.2% for bullous keratopathy, and 8.7% and 22.2% for Fuch’s dystrophy, respectively. Also, best visual acuity was looked at in patients with rejection episodes. None of the patients had a pre-op visual acuity 20/40 or better; however, post-op PKP 2 (8.7%) of patients achieved 20/40 or better. Also, 4 (17.4%) of patients had a pre-op visual acuity between 20/50 and 20/150, but post-op PKP best visual acuity between 20/50 and 20/150 was increased to 9 (39.1%). Conclusion At 36% the prevalence of corneal graft rejection was one of the highest in the reported literature. But only 14% of those episodes resulted in graft failure which is one of the lowest in the published literature. This study demonstrates that patients of African ancestry may have a higher rejection rate which does not necessarily result in graft failure. PMID:23960938

Corneal graft rejection in African Americans at Howard University Hospital.

PubMed

Ferdinand, Larry; Ngakeng, Vanessa; Copeland, Robert A

2011-07-01

There is scarcity of data in the literature on cornel graft rejection rate in patients exclusively of African ancestry. The purpose of this study was to evaluate the rejection rate of corneal transplant surgery performed at Howard University Hospital on such patients over a 15 year period. A retrospective evaluation was performed of the cornea graft rejection and corneal graft failure rate in 125 penetrating keratoplasties (PKPs) done by one corneal specialist at Howard University Hospital from January 1, 1990 to August 31, 2005. Of the 125 patients, 62 were eliminated from the study because of re-grafted eyes, non-African descent, primary graft failures, follow-up less than 1 month and lack of availability of charts. This study, therefore, studied and recorded data from 63 penetrating keratoplasties of 63 eyes from 60 patients. Episodes of graft rejection were documented in 23 eyes (36.5% of cases). Nine out of the 23 graft rejections manifested to secondary graft failure (39%). Overall, there were nine out of the 63 PKPs (14.3%) that resulted in secondary graft failure over the past 15 years. The major diagnostic categories were bullous keratopathy 24 (38%), keratoconus 10 (15.8%), Fuch's dystrophy 4 (6.3%), other 20 (31.7%). Of the cases with episodes of rejection and failure, 4.3% and none were attributable to keratoconus, 30.4% and 22.2% for bullous keratopathy, and 8.7% and 22.2% for Fuch's dystrophy, respectively. Also, best visual acuity was looked at in patients with rejection episodes. None of the patients had a pre-op visual acuity 20/40 or better; however, post-op PKP 2 (8.7%) of patients achieved 20/40 or better. Also, 4 (17.4%) of patients had a pre-op visual acuity between 20/50 and 20/150, but post-op PKP best visual acuity between 20/50 and 20/150 was increased to 9 (39.1%). At 36% the prevalence of corneal graft rejection was one of the highest in the reported literature. But only 14% of those episodes resulted in graft failure which is one of the lowest in the published literature. This study demonstrates that patients of African ancestry may have a higher rejection rate which does not necessarily result in graft failure.

Vulval lichen planus-lichen sclerosus overlap.

PubMed

Howard, Matthew; Hall, Anthony

2018-01-01

Vulval lichen planus-lichen sclerosus overlap is an emerging observation. Few clinical reports exist with no reviews of literature. We present a focused update of this phenomenon and discuss a clinical case. We report a 63-year-old woman with a 20-year history of ulcerative vulvo-vaginitis, initially diagnosed as benign mucous membrane (cicatricial) pemphigoid. This led to prolonged treatment with oral corticosteroids with minimal improvement in symptoms. Subsequent complications of long-term use of systemic corticosteroid ensued. A clinico-pathological diagnosis of severe erosive lichen planus was made on clinical findings and on non-specific biopsy changes of ulceration and inflammation. Treatment with topical clobetasol propionate 0.05% ointment twice daily led to dramatic improvement of ulceration, easing of discomfort and marked improvement in quality of life. Clinical examination revealed Wickham's striae on the labia majora supporting the diagnosis. Six years after commencement of topical clobetasol, white plaques were noticed on the labia majora, perineum and peri-anal region consistent with lichen sclerosus, confirmed by repeat vulval skin biopsy and on vulvectomy. This case highlights the challenge of diagnosis of extensive vulvo-vaginal ulceration and the necessity to re-examine a previous diagnosis if there is poor response to treatment.

[Severe contact-allergy dermatitis due to poison ivy--a plant that is rarely encountered in The Netherlands; a family history].

PubMed

Leclercq, R M F M

2005-07-23

In successive years, three members of the same family (a man and woman aged 46 years and their son, aged 20) constantly developed severe pruritic, erythematous, vesicular and bullous dermatitis in the spring and summer after working in the garden. Although the findings were consistent with a photophytotoxic dermatitis, the causative plant remained unclear. Oral therapy with high doses ofprednisolone was necessary. When the man travelled to the USA and visited a doctor there, he recognised the symptoms as those of contact dermatitis caused by poison ivy (Toxicodendron radicans), a plant that is found sporadically in the wild state in Europe. Their grandparents had brought the plant back from a trip to the USA and planted it in the garden because of the beautiful fall colours. The family identified the plant via a search on Internet and eliminated it from the garden completely. Since then, the family has no longer suffered from contact-allergy dermatitis.

Chandelier Illumination for Descemet Membrane Endothelial Keratoplasty

PubMed Central

Hayashi, Takahiko; Yuda, Kentaro; Tsuchiya, Ayako; Oyakawa, Itaru; Mizuki, Nobuhisa; Kato, Naoko

2017-01-01

Purpose: To describe a simple technique that uses posterior chandelier illumination during Descemet membrane endothelial keratoplasty in cases of severe bullous keratopathy (BK). Methods: Five eyes of 4 patients with advanced BK undergoing Descemet membrane endothelial keratoplasty were retrospectively analyzed. The pupil of the host eye was not treated with mydriatic or miotic agents. The chandelier illuminator was inserted transconjunctivally into the vitreous cavity from the pars plana. Results: In all eyes, BK was secondary to laser iridotomy, which was performed for prevention or treatment of angle closure glaucoma. The implanted graft was clearly confirmed in the anterior chamber using activated chandelier illumination. The graft was immediately attached to the host cornea, with eventual healing of BK in all eyes. No complication involving insertion or removal of the 25-gauge trocar and the chandelier illuminator was observed. No vision-threatening complication was observed in any of the 5 eyes. Conclusions: The chandelier illuminator provided good visibility of the anterior chamber and enhanced the safety of surgery by preventing formation of an inverted graft. PMID:28644235

Molecular Diagnosis in Autoimmune Skin Blistering Conditions

PubMed Central

Otten, J.V.; Hashimoto, T.; Hertl, M.; Payne, A.S.; Sitaru, C.

2014-01-01

Blister formation in skin and mucous membranes results from a loss of cell-cell or cell-matrix adhesion and is a common outcome of pathological events in a variety of conditions, including autoimmune and genetic diseases, viral and bacterial infections, or injury by physical and chemical factors. Autoantibodies against structural components maintaining cell-cell and cell-matrix adhesion induce tissue damage in autoimmune blistering diseases. Detection of these autoantibodies either tissue-bound or circulating in serum is essential to diagnose the autoimmune nature of disease. Various immunofluorescence methods as well as molecular immunoassays, including enzyme-linked immunosorbent assay and immunoblotting, belong to the modern diagnostic algorithms for these disorders. There is still a considerable need to increase awareness of the rare autoimmune blistering diseases, which often show a severe, chronic-relapsing course, among physicians and the public. This review article describes the immunopathological features of autoimmune bullous diseases and the molecular immunoassays currently available for their diagnosis and monitoring. PMID:24160488

Legalizing Cannabis: A physician's primer on the pulmonary effects of marijuana.

PubMed

Lutchmansingh, Denyse; Pawar, Leena; Savici, Dana

2014-01-01

Habitual smoking of marijuana is associated with multiple respiratory symptoms such as cough, sputum production, and wheezing .These symptoms are not significantly different from those exhibited by tobacco smokers. Furthermore, endobronchial biopsies of habitual smokers of marijuana and /or tobacco have shown that both marijuana and cigarette smoking cause significant bronchial mucosal histopathology and that these effects are additive. Although marijuana smokers have minimal changes in pulmonary function studies as compared to tobacco smokers, they may develop bullous disease and spontaneous pneumothoraces. The relationship between marijuana smoking and lung cancer remains unclear due to design limitations of the studies published so far. These findings should warn individuals that marijuana smoking may result in serious short-term and long-term respiratory complications, and habitual marijuana use should be viewed with caution. The medical literature so far does not support routine evaluation by pulmonary function tests or imaging studies; until more definitive data is available, we do not recommend the regular use of these tests in the evaluation of habitual marijuana smokers.

Tissue response to aqueous drainage in a functioning Molteno implant.

PubMed Central

Loeffler, K U; Jay, J L

1988-01-01

The tissue reaction to a functioning Molteno implant has been studied by light microscopy and by scanning and transmission electron microscopy. The material was obtained from an aphakic 83-year-old human eye which required enucleation because of intractable bullous keratopathy, despite well controlled intraocular pressure. The tissue response around the silicone rubber tube was that of simple fibroblastic activity. Around the implant, however, there was fibrous tissue in which necrotic cell debris was prominent. No significant inflammation was observed in this tissue, but the choroid beneath the implant showed a focal inflammatory cell infiltrate. The morphology suggests that the tissue around all surfaces of the implant (450 mm2) is exposed to aqueous, which seems to have a toxic effect on the encapsulating connective tissue. The changes seen in the tissue exposed to draining aqueous are similar to those described in experimental studies of the effect of aqueous on cell growth in tissue culture. Images PMID:3342217

A Pathophysiologic Role for Epidermal Growth Factor Receptor in Pemphigus Acantholysis*

PubMed Central

Bektas, Meryem; Jolly, Puneet S.; Berkowitz, Paula; Amagai, Masayuki; Rubenstein, David S.

2013-01-01

The pemphigus family of autoimmune bullous disorders is characterized by autoantibody binding to desmoglein 1 and/or 3 (dsg1/dsg3). In this study we show that EGF receptor (EGFR) is activated following pemphigus vulgaris (PV) IgG treatment of primary human keratinocytes and that EGFR activation is downstream of p38 mitogen-activated protein kinase (p38). Inhibition of EGFR blocked PV IgG-triggered dsg3 endocytosis, keratin intermediate filament retraction, and loss of cell-cell adhesion in vitro. Significantly, inhibiting EGFR prevented PV IgG-induced blister formation in the passive transfer mouse model of pemphigus. These data demonstrate cross-talk between dsg3 and EGFR, that this cross-talk is regulated by p38, and that EGFR is a potential therapeutic target for pemphigus. Small-molecule inhibitors and monoclonal antibodies directed against EGFR are currently used to treat several types of solid tumors. This study provides the experimental rationale for investigating the use of EGFR inhibitors in pemphigus. PMID:23404504

A COL7A1 Mutation Causes Dystrophic Epidermolysis Bullosa in Rotes Höhenvieh Cattle

PubMed Central

Menoud, Annie; Welle, Monika; Tetens, Jens; Lichtner, Peter; Drögemüller, Cord

2012-01-01

We identified a congenital mechanobullous skin disorder in six calves on a single farm of an endangered German cattle breed in 2010. The condition presented as a large loss of skin distal to the fetlocks and at the mucosa of the muzzle. All affected calves were euthanized on humane grounds due to the severity, extent and progression of the skin and oral lesions. Examination of skin samples under light microscopy revealed detachment of the epidermis from the dermis at the level of the dermo epidermal junction, leading to the diagnosis of a subepidermal bullous dermatosis such as epidermolysis bullosa. The pedigree was consistent with monogenic autosomal recessive inheritance. We localized the causative mutation to an 18 Mb interval on chromosome 22 by homozygosity mapping. The COL7A1 gene encoding collagen type VII alpha 1 is located within this interval and COL7A1 mutations have been shown to cause inherited dystrophic epidermolysis bullosa (DEB) in humans. A SNP in the bovine COL7A1 exon 49 (c.4756C>T) was perfectly associated with the observed disease. The homozygous mutant T/T genotype was exclusively present in affected calves and their parents were heterozygous C/T confirming the assumed recessive mode of inheritance. All known cases and genotyped carriers were related to a single cow, which is supposed to be the founder animal. The mutant T allele was absent in 63 animals from 24 cattle breeds. The identified mutation causes a premature stop codon which leads to a truncated protein representing a complete loss of COL7A1 function (p.R1586*). We thus have identified a candidate causative mutation for this genetic disease using only three cases to unravel its molecular basis. Selection against this mutation can now be used to eliminate the mutant allele from the Rotes Höhenvieh breed. PMID:22715415

Useful Interplay Between Spontaneous ADR Reports and Electronic Healthcare Records in Signal Detection.

PubMed

Pacurariu, Alexandra C; Straus, Sabine M; Trifirò, Gianluca; Schuemie, Martijn J; Gini, Rosa; Herings, Ron; Mazzaglia, Giampiero; Picelli, Gino; Scotti, Lorenza; Pedersen, Lars; Arlett, Peter; van der Lei, Johan; Sturkenboom, Miriam C; Coloma, Preciosa M

2015-12-01

Spontaneous reporting systems (SRSs) remain the cornerstone of post-marketing drug safety surveillance despite their well-known limitations. Judicious use of other available data sources is essential to enable better detection, strengthening and validation of signals. In this study, we investigated the potential of electronic healthcare records (EHRs) to be used alongside an SRS as an independent system, with the aim of improving signal detection. A signal detection strategy, focused on a limited set of adverse events deemed important in pharmacovigilance, was performed retrospectively in two data sources-(1) the Exploring and Understanding Adverse Drug Reactions (EU-ADR) database network and (2) the EudraVigilance database-using data between 2000 and 2010. Five events were considered for analysis: (1) acute myocardial infarction (AMI); (2) bullous eruption; (3) hip fracture; (4) acute pancreatitis; and (5) upper gastrointestinal bleeding (UGIB). Potential signals identified in each system were verified using the current published literature. The complementarity of the two systems to detect signals was expressed as the percentage of the unilaterally identified signals out of the total number of confirmed signals. As a proxy for the associated costs, the number of signals that needed to be reviewed to detect one true signal (number needed to detect [NND]) was calculated. The relationship between the background frequency of the events and the capability of each system to detect signals was also investigated. The contribution of each system to signal detection appeared to be correlated with the background incidence of the events, being directly proportional to the incidence in EU-ADR and inversely proportional in EudraVigilance. EudraVigilance was particularly valuable in identifying bullous eruption and acute pancreatitis (71 and 42 % of signals were correctly identified from the total pool of known associations, respectively), while EU-ADR was most useful in identifying hip fractures (60 %). Both systems contributed reasonably well to identification of signals related to UGIB (45 % in EudraVigilance, 40 % in EU-ADR) but only fairly for signals related to AMI (25 % in EU-ADR, 20 % in EudraVigilance). The costs associated with detection of signals were variable across events; however, it was often more costly to detect safety signals in EU-ADR than in EudraVigilance (median NNDs: 7 versus 5). An EHR-based system may have additional value for signal detection, alongside already established systems, especially in the presence of adverse events with a high background incidence. While the SRS appeared to be more cost effective overall, for some events the costs associated with signal detection in the EHR might be justifiable.

Osteo-odonto-keratoprosthesis - a maxillofacial perspective.

PubMed

Narayanan, Vinod; Nirvikalpa, Natarajan; Rao, Srinivas K

2012-12-01

The OOKP (osteo-odonto-keratoprosthesis) is the treatment of choice for conditions like Stevens-Johnson syndrome, ocular cicatricial pemphigoid, trachoma, multiple failed grafts and chemical burns which are not amenable to penetrating keratoplasty. The OOKP is an autograft which replaces the cornea with a polymethacrylate cylinder mounted on a tooth-bone complex. The aim of this paper was to retrospectively analyze the records in 26 patients undergoing OOKP surgery between 2007 and 2011. The paper describes our experience with the procedure, with emphasis on its oral and maxillofacial aspects and management of associated complications. The aetiology of blindness in 23 patients was Stevens-Johnson's syndrome and chemical burns in three. Twenty-two patients had their maxillary canines, two had mandibular canines and two had maxillary first premolars as the choice of donor tooth. An oroantral fistula developed in four patients. One patient needed to undergo a surgical procedure for closure of the same. Roots of adjacent teeth were exposed in 12 patients. Twenty-four patients underwent both stages of the procedure with 19 being visually rehabilitated successfully. There was no improvement in the vision of four patients. One patient was lost to follow-up. Two patients have yet to undergo Stage 2. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Subgingival Microbiota in White Patients With Desquamative Gingivitis: A Cross-Sectional Study.

PubMed

Arduino, Paolo G; Romano, Federica; Sasia, Danilo; Broccoletti, Roberto; Ricceri, Fulvio; Barbui, Anna Maria; Brossa, Silvia; Cipriani, Raffaella; Cricenti, Luca; Cabras, Marco; Aimetti, Mario

2017-07-01

Presence of epithelial desquamation, erythema, and erosions on gingival tissue is usually described in the literature as desquamative gingivitis (DG). A wide range of autoimmune/dermatologic disorders can manifest as DG, although the two more common are oral lichen planus and mucous membrane pemphigoid. The aim of this study is to investigate prevalence of 11 periodontopathogenic microorganisms in patients with DG and to compare it with the microbiologic status of individuals affected by plaque-induced gingivitis (pGI). Cross-sectional clinical and microbiologic data were obtained from 66 patients (33 in each group). Subgingival plaque samples were analyzed using semiquantitative polymerase chain reaction analysis. Statistically significant difference, but with little clinical significance, was observed in gingival conditions between the two groups, probably due to the worse home control hygiene of patients with DG. Prevalence and levels of Aggregatibacter actinomycetemcomitans, Eikenella corrodens, and Fusobacterium nucleatum/periodonticum were statistically higher in samples from patients with DG than in those with pGI. In multivariate regression models, subgingival colonization of A. actinomycetemcomitans and F. nucleatum/periodonticum was not statistically associated with DG, whereas, high levels of E. corrodens were associated with 13-fold increased odds for DG. Microbiologic differences were found in subgingival plaque for patients with DG and pGI. This may suggest possible association between periodontal pathogens and DG.

First case of fungal keratitis caused by Pestalotiopsis clavispora.

PubMed

Monden, Yu; Yamamoto, Shohaku; Yamakawa, Ryoji; Sunada, Atsuko; Asari, Seishi; Makimura, Koichi; Inoue, Yoshitsugu

2013-01-01

To report the isolation of Pestalotiopsis clavispora from the cornea of a patient with recurrent keratitis. A 73-year-old male gardener presented with conjunctival injection and an oval infiltrate with feathery margins in the temporal half of the cornea in the right eye. His ocular history in the right eye included cataract surgery, five episodes of herpes simplex keratitis, three glaucoma surgeries, and bullous keratopathy. He had been treated with corticosteroids for years. Light microscopy of corneal scrapings revealed a filamentous fungus, and fungal keratitis was diagnosed. Treatment with topical voriconazole and pimaricin ointment was commenced. One month later, the infiltrate resolved. The antifungal agents were discontinued 7 months later, and keratitis relapsed 4 days after the discontinuation. The fungus was isolated and identified by molecular techniques as P. clavispora. Based on the results of antifungal susceptibility testing, treatment with topical and intravenous micafungin was initiated. The corneal infiltrate resolved 1 month after the relapse. Molecular identification of the pathogen, and antifungal susceptibility testing, are useful in treating patients with fungal keratitis caused by a rare human pathogen.

First case of fungal keratitis caused by Pestalotiopsis clavispora

PubMed Central

Monden, Yu; Yamamoto, Shohaku; Yamakawa, Ryoji; Sunada, Atsuko; Asari, Seishi; Makimura, Koichi; Inoue, Yoshitsugu

2013-01-01

Purpose To report the isolation of Pestalotiopsis clavispora from the cornea of a patient with recurrent keratitis. Case report A 73-year-old male gardener presented with conjunctival injection and an oval infiltrate with feathery margins in the temporal half of the cornea in the right eye. His ocular history in the right eye included cataract surgery, five episodes of herpes simplex keratitis, three glaucoma surgeries, and bullous keratopathy. He had been treated with corticosteroids for years. Light microscopy of corneal scrapings revealed a filamentous fungus, and fungal keratitis was diagnosed. Treatment with topical voriconazole and pimaricin ointment was commenced. One month later, the infiltrate resolved. The antifungal agents were discontinued 7 months later, and keratitis relapsed 4 days after the discontinuation. The fungus was isolated and identified by molecular techniques as P. clavispora. Based on the results of antifungal susceptibility testing, treatment with topical and intravenous micafungin was initiated. The corneal infiltrate resolved 1 month after the relapse. Conclusion Molecular identification of the pathogen, and antifungal susceptibility testing, are useful in treating patients with fungal keratitis caused by a rare human pathogen. PMID:24348013

[Anti-TNF alpha in dermatology].

PubMed

Mahe, E; Descamps, V

2002-12-01

The discovery of the major role of TNF alpha in the physiopathology of certain inflammatory diseases and notably in rheumatoid arthritis and Crohn's disease has led to the development of anti-TNF alpha drugs. These new therapeutic arms issued from bio-technology have rapidly demonstrated their efficacy in the treatment of these two diseases. The anti-TNF alpha arsenal is currently dominated by etanercept, a fusion protein composed of a soluble TNF alpha receptor, and infliximab, a chimeric monoclonal antibody. However, new molecules will soon enrich this arsenal. TNF alpha is a major cytokine of inflammatory diseases of the skin. Many dermatological diseases will probably benefit from these new treatments. Two studies have already demonstrated their interest in cutaneous and articular psoriasis. Encouraging sporadic results suggest other potential indications (Behcet's disease, bullous dermatitis, neutrophilic dermatitis, toxic epidermal necrolysis, systemic vascularitis,.). These promising new treatments, although expensive, and with yet unknown long term side effects, justify rigorous assessment of their efficacy and tolerance in each indication. Here again the dermatologist has a major role to play in post-marketing pharmacovigilance.

Cardiomyopathy in Patients With Hereditary Bullous Epidermolysis.

PubMed

Batalla, A; Vicente, A; Bartrons, J; Prada, F; Fortuny, C; González-Enseñat, M A

In recent decades, an association has been reported between epidermolysis bullosa (EB) and dilated cardiomyopathy (DC). DC is typically in an advanced phase when detected, leading to a poorer prognosis. Our objective was to determine the prevalence of DC in patients with EB seen in Hospital San Joan de Déu in Barcelona, Spain, between May 1986 and April 2015. This was a descriptive, cross-sectional chart-review study in which we recorded the type and main subtypes of EB and the presence or absence of DC. Fifty-seven patients with EB were found, 19 with EB simplex, 10 with junctional EB, 27 with dystrophic EB (14 dominant dystrophic and 13 recessive dystrophic), and just 1 with Kindler syndrome. DC was detected in only 2 patients with recessive dystrophic EB. Twenty-three patients had presented factors that could have had a causal relationship with the potential onset of DC. DC is a possible complication of EB, particularly in recessive dystrophic EB. Periodic follow-up should be performed to make an early diagnosis and start treatment. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Outpatient pediatric community-acquired methicillin-resistant Staphylococcus aureus: a polymorphous clinical disease.

PubMed

Groner, Abraham; Laing-Grayman, Deborah; Silverberg, Nanette B

2008-02-01

Community-acquired methicillin-resistant Staphylococcus aureus (CAMRSA) presents numerous diagnostic and therapeutic problems for the outpatient physician, including the appropriate use of antibiotics and proper counseling of families on ways to prevent household spread. Most cases of CAMRSA in children involve soft tissue and skin infection, which is precisely the type of infection most likely to be diagnosed in a dermatology practice. We reviewed 8 pediatric cases of cutaneous CAMRSA that presented over 8 months. The 8 pediatric patients presented with one or more of the following: folliculitis (n=4), abscesses of the groin (n=3), impetiginized atopic dermatitis (AD)(n=2), pustules (n=2), bullous impetigo (n= 1), and nonbullous impetigo (n=1). Three caregivers of these children developed abscesses in exposed areas such as the forearm (n=3) and calf (n=1). The folliculitis cases involved the abdomen, groin and diaper region, buttocks, and inner thighs; the impetiginized AD did not differ from the distribution of the AD. The variety of clinical presentations and the spread in households represent a few of the many facets of CAMRSA in the pediatric dermatology outpatient setting.

[Acute skin infections and their imitators in children : A photo quiz].

PubMed

Theiler, M; Schwieger-Briel, A; Weibel, L

2017-10-01

Skin infections account for 40% of emergency visits in pediatric dermatology. It is important to promptly recognize skin infections with potential complications and initiate treatment. However some characteristic skin findings may imitate skin infections and are often misdiagnosed. To illustrate frequent pediatric skin infections and pitfalls in view of imitators and differential diagnoses. A photo quiz is presented with the discussion of a selection of acute pediatric skin infections in comparison to their infectious or noninfectious differential diagnoses. The following infectious skin conditions and imitators are described and clinical clues for differentiation highlighted: eczema herpeticum and bacterial superinfection of atopic dermatitis; exanthematous hand, foot and mouth disease and varicella infection; erythema chronicum multilocularis and anular urticaria; Gianotti-Crosti syndrome and Gianotti-Crosti-like reaction; bacterial folliculitis of the scalp and kerion celsi and eosinophilic pustular folliculitis of the scalp; cutaneous Leishmaniasis and idiopathic facial aseptic granuloma; allergic and bacterial lymphangitis; bullous impetigo contagiosa and nonaccidental scalding. Careful anamnesis and skin examination with attention to the here illustrated differential diagnoses are essential to avoid pitfalls in the evaluation of acute pediatric skin infections.

Prevalence of oral lichen planus in Iranian children and adolescents: a 12-year retrospective study.

PubMed

Bakhtiari, S; Taheri, J B; Toossi, P; Azimi, S; Kawosi Nezhad, Sh

2017-12-01

To investigate the prevalence of oral lichen planus in patients younger than 18 years, referred to a dermatology centre in Iran during 2002-2014. Lichen planus is a chronic inflammatory, immune-mediated disease that could affect the oral mucosa and is a pre-cancerous condition. The disease usually develops in middle age with female predominance and is rare in children. In this retrospective study, cases with definitive histopathologic diagnosis of lichen planus, over a 12-year period from 2002 to 2014 from a dermatologic hospital archive were evaluated. The prevalence of both cutaneous and oral lichen planus, the male:female ratio and site of involvement were calculated using SPSS version 21. Thirty-six of 564 patients younger than 18 years old diagnosed with lichen planus. Two females (0.4%) had oral lichen planus. One patient had erosive, and one had bullous, oral lichen planus. Oral lichen planus had a very low frequency in Iranian population younger than 18 years old, identifying these patients is recommended for long-term follow-up.

[Terbinafine : Drug-induced lupus erythematodes and triggering of psoriatic skin lesions].

PubMed

Mayser, P

2016-09-01

Based on the technical information that oral terbinafine must be used with caution in patients with pre-existing psoriasis or lupus erythematosus, the literature was summarized. Terbinafine belongs to the drugs able to induce subcutaneous lupus erythematosus (SCLE)-with a relatively high risk. The clinical picture of terbinafine-induced SCLE may be highly variable and can also include erythema exsudativum multiforme-like or bullous lesions. Thus, differentiation of terbinafine-induced Stevens-Johnson syndrome or toxic epidermal necrolysis may be difficult. Therefore, terbinafine should be prescribed with caution in patients who show light sensitivity, arthralgias, positive antinuclear antibodies or have a history of SLE or SCLE. Case reports include wide-spread, but mostly nonlife-threatening courses, which did not require systemic therapy with steroids or antimalarials in every case. Terbinafine is also able to induce or to aggravate psoriasis. The latency period seems to be rather short (<4 weeks). Terbinafine therefore is not first choice if a systemic therapy with antimycotics is indicated in a patient with psoriasis or psoriatic diathesis. Azole derivatives according to the guidelines may be used as an alternative.

Prayer marks.

PubMed

Abanmi, Abdullah A; Al Zouman, Abdulrahman Y; Al Hussaini, Husa; Al-Asmari, Abdulrahman

2002-07-01

Prayer marks (PMs) are asymptomatic, chronic skin changes that consist mainly of thickening, lichenification, and hyperpigmentation, and develop over a long period of time as a consequence of repeated, extended pressure on bony prominences during prayer. Three hundred and forty-nine Muslims and 24 non-Muslims were examined for the appearance of PMs at different body sites. The prospective study of 349 Muslims (both males and females) with regular praying habits showed the occurrence of PMs on specific locations, such as the forehead, knees, ankles, and dorsa of the feet, leading to dermatologic changes consisting of lichenification and hyperpigmentation. The incidence of PMs was significantly higher in males than in females. Older subjects (over 50 years of age) demonstrated a significantly higher frequency of lichenification and hyperpigmentation, suggesting that repeated pressure and friction for prolonged periods are the causative factors for the development of PMs. Histologic examination of skin biopsies from the affected sites showed compact orthokeratosis, hypergranulosis, dermal papillary fibrosis, and dermal vascularization. PMs were not associated with any risk of secondary complications, such as erythema, bullous formation, and infections. PMs are commonly occurring dermatologic changes in Muslims who pray for prolonged periods.

Complement Activation in Inflammatory Skin Diseases

PubMed Central

Giang, Jenny; Seelen, Marc A. J.; van Doorn, Martijn B. A.; Rissmann, Robert; Prens, Errol P.; Damman, Jeffrey

2018-01-01

The complement system is a fundamental part of the innate immune system, playing a crucial role in host defense against various pathogens, such as bacteria, viruses, and fungi. Activation of complement results in production of several molecules mediating chemotaxis, opsonization, and mast cell degranulation, which can contribute to the elimination of pathogenic organisms and inflammation. Furthermore, the complement system also has regulating properties in inflammatory and immune responses. Complement activity in diseases is rather complex and may involve both aberrant expression of complement and genetic deficiencies of complement components or regulators. The skin represents an active immune organ with complex interactions between cellular components and various mediators. Complement involvement has been associated with several skin diseases, such as psoriasis, lupus erythematosus, cutaneous vasculitis, urticaria, and bullous dermatoses. Several triggers including auto-antibodies and micro-organisms can activate complement, while on the other hand complement deficiencies can contribute to impaired immune complex clearance, leading to disease. This review provides an overview of the role of complement in inflammatory skin diseases and discusses complement factors as potential new targets for therapeutic intervention. PMID:29713318

A Study of Intercellular Spaces in the Rabbit Jejunum during Acute Volume Expansion and after Treatment with Cholera Toxin

PubMed Central

DiBona, Donald R.; Chen, Lincoln C.; Sharp, Geoffrey W. G.

1974-01-01

The effects of acute volume expansion and of intraluminal administration of cholera toxin have been examined in rabbit jejunum. Acute volume expansion was shown to reverse the normal reabsorptive flux of water and cause significant fluid secretion. Phase and electronmicroscopic examination of the jejunal epithelium showed that marked distension of the intercellular spaces had occurred. Examination of the jejunal epithelium after treatment with cholera toxin showed that, in association with high rates of fluid secretion, the intercellular spaces were extremely small and lateral membranes of adjacent cells were in close apposition to one another. Thus the mechanisms of fluid secretion in these two situations would appear to be quite different. The secretion associated with volume expansion, and accompanied by a rise in venous pressure and bullous deformations of terminal junctions, could well be due to hydrostatic pressure applied through intercellular channels. The secretion of cholera appears to be unrelated to hydrostatic pressure and is more likely due to body-to-lumen active ion transport. Images PMID:4596506

Acute native lung hyperinflation is not associated with poor outcomes after single lung transplant for emphysema.

PubMed

Weill, D; Torres, F; Hodges, T N; Olmos, J J; Zamora, M R

1999-11-01

Single-lung transplantation for emphysema may be complicated by acute native lung hyperinflation (ANLH) with hemodynamic and ventilatory compromise. Some groups advocate the routine use of independent lung ventilation, double-lung transplant, or right-lung transplant with or without contralateral lung volume reduction surgery in high-risk patients. The goal of this study was to determine the incidence of ANLH and identify its potential predictors. We reviewed 51 consecutive single-lung transplants for emphysema. Symptomatic ANLH was defined as mediastinal shift and diaphragmatic flattening on chest x-ray with hemodynamic or respiratory failure requiring cardiopressor agents or independent lung ventilation. Preoperative and postoperative physiologic and hemodynamic data were analyzed from both recipients and donors. Sixteen patients developed radiographic ANLH; 8 were symptomatic, 2 severely so. We could not identify high-risk patients before transplant by pulmonary function tests, predicted donor total lung capacity (TLC)/actual recipient TLC ratio, pulmonary artery pressures, or the side transplanted. There was a trend toward an increased incidence of symptomatic ANLH in patients with bullous emphysema on chest computed tomography, but this was accounted for primarily by patients with alpha1-antitrypsin deficiency (4/13 vs 4/38 with chronic obstructive pulmonary disease, P = 0.10). No patient required cardiopulmonary bypass or inhaled nitric oxide intraoperatively. Patients with acute native lung hyperinflation did not have increased reperfusion edema as measured by chest x-ray score or PaO2/F(I)O2 ratio. Compared to patients without ANLH, symptomatic patients had longer ventilator times (64.9+/-14.6 hours vs 40.4+/-3.9, P = 0.02, ANOVA) and longer lengths of stay (19.3+/-2.1 days vs 13.7+/-1.3, P = 0.07), but 30-day survival was 100%. Two symptomatic patients required independent lung ventilation or inhaled nitric oxide; the others were managed with decreased minute ventilation, early extubation, and cardiopressor agents. No patient required early lung volume reduction surgery or retransplantation. Acute native lung hyperinflation had no effect on FEV1 or 6-minute walk results at 1 year; survival at 1, 2, or 3 years; or the rate of acute rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. Acute native lung hyperinflation is common radiographically but is rarely clinically severe. Although there was a trend toward an increase in symptomatic ANLH in patients with bullous emphysema, a high-risk group could not be identified preoperatively. Our results do not support the routine use of bilateral lung transplant, the exclusive use of right single-lung transplant, simultaneous lung volume reduction surgery, or independent lung ventilation for patients with emphysema. Management strategies should be employed that limit overdistension of the native lung and lead to early extubation.

Generalized Pyoderma Gangrenosum Associated with Ulcerative Colitis: Successful Treatment with Infliximab and Azathioprine.

PubMed

Chatzinasiou, Foteini; Polymeros, Dimitrios; Panagiotou, Maro; Theodoropoulos, Konstadinos; Rigopoulos, Dimitrios

2016-04-01

Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, part of the spectrum of neutrophilic and auto-inflammatory dermatoses. Its pathogenesis is unknown, although immune pathways have been implicated. Lesion biopsies show a predominantly neutrophilic infiltrate. The incidence of PG is uncertain, but it is estimated to be 3-10 per million per year, occurring at any age but most commonly between 20 and 50 years with a possible slightly higher incidence in women. Approximately 50% of patients with PG also have another disease associated with PG. The most common is inflammatory bowel disease (IBD), particularly Crohn's and ulcerative colitis (UC). Local treatment may be sufficient for mild cases, while for severe cases systemic immunosuppressants are the mainstay (1,2). We report the case of a patient with bullous PG and UC successfully treated with infliximab and azathioprine. A 32-year-old male Caucasian patient presented with painful violaceous vesicles and enlarging bullae of various sizes and with acute onset, located on the trunk and bilaterally on both the lower and the upper extremities. Lesions on the trunk were composed of hemorrhagic pustules with a surrounding erythematous overhanging border. Some of the lesions had undergone central necrosis and ulceration (Figure 1, a-d). The patient reported of the lesions had appeared one week ago, simultaneously with the exacerbation of a known inflammatory bowel disease with hemorrhagic mucoid diarrhea and fever of up to 38.5°C. The patient's medical history included UC affecting the whole colon (pancolitis), diagnosed 5 months prior to the onset of the epidermal lesions, for which the patient was receiving treatment with oral prednisolone 10 mg/day and mesalazine granules. Blood tests showed severe anemia, leukocytosis, and increased inflammatory markers (C-reactive protein, erythrocyte sedimentation rate). Antinuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA) andtibodies, antineutrophil cytoplasmic antibodies (cANCA), perinuclear neutrophil antibodies (p-ANCA), antiphospholipid antibodies, and tumor markers were within normal limits. The patient was negative for cryoglobulins, viral hepatitis (B, C) and human immunodeficiency virus (HIV). Blood cultures were negative. Microscopy and cultures for mycobacteria and fungi gave negative results. Stool samples tested negative for infections agents. The Mantoux skin test was negative. Colonoscopy showed severe pancolitis, and biopsies from the rectum and sigmoid colon were consistent with chronic ulcerative colitis. Abdominal ultrasound and chest and abdominal X-rays did not result in significant findings. Because of severe anemia, the patient received 2 blood transfusions. The histopathologic examination carried out on the erythematous border of a lesion on the lower leg showed a neutrophilic infiltrate, confined to the dermis. On the basis of clinical findings, the diagnosis of PG was established. Topical wound care consisted of local wound care and a topical corticosteroid. Systemic therapy was initiated with 40 mg/day methylprednisolone for 7 days, 30 mg/day for 7 days, then 25 mg/day, and then tapered down further. The patient received an infusion of infliximab 7.5 mg/kg at weeks 0, 2, and 6 and every 8 weeks thereafter. After week 2, oral azathioprine 2.5 mg/kg daily was added to the treatment. The patient also received mesalazine tablets (2 g ×2/day) and mesalazine enema (1-2/day). The patient showed good response to treatment, with clinical remission of skin lesions. Lesions healed with characteristic thin, atrophic scars (Figure 2, a-d). At 7-month follow-up the patient was continuing with infusions of infliximab 7.5 mg/kg and azathioprine 2.5 mg/kg and was still in remission. We reported our experience with a case of generalized bullous pyoderma gangrenosum associated with ulcerative colitis. Generalized pyoderma gangrenosum is very rare. Bullous or atypical PG was first described by Perry and Winklemann in 1972 (1). Brunsting et al. coined the term pyoderma gangrenosum (PG) to describe a series of patients with recurrent ulcerations (3). The incidence of this disease is uncertain. Its pathogenesis is unknown, but an immunological background has been suggested. In approximately 50% of patients, an underlying immunological disease is present, commonly inflammatory bowel disease (IBD) (4-6). In larger series of patients with PG, approximately 50% present with a primary disorder. Ulcerative colitis is found in 10-15% of cases. Crohn's disease is associated with PG closed than UC. Less than 3% of patients with Crohn's disease or UC develop PG (6). PG is characterized by cutaneous ulcerations with mucopurulent or hemorrhagic exudate. It begins as an inflammatory pustule with a surrounding halo that enlarges and begins to ulcerate. These very painful ulcers present with undermined bluish borders with surrounding erythema. The lesions of PG most commonly occur on the legs, but they may occur anywhere on the body. The clinical picture of PG is very characteristic. Therefore the diagnosis of PG is based firstly on clinical signs and on the patient's history of underlying diseases and then supported by biopsy. PG has four distinctive clinical and histological variants. Some have morphological and histological features that overlap with other reactive neutrophilic skin conditions. There are no diagnostic serologic features (6,7). There is no evidence that the efficacy of treatment strategies for PG differs between IBD and non-IBD patients. For patients with a diffuse disease or rapidly progressive process, systemic treatment is essential. Immunosuppression is the mainstay of treatment. Traditionally, the most commonly used drugs with the best clinical experience are systemic corticosteroids. Corticosteroids have been considered as first line treatment (6,8). As reported by the European Crohn's and Colitis Organisation (ECCO) in 2008, an evidence-based consensus on the management of special situations in patients with ulcerative colitis, systemic corticosteroids are recommended (9). Treatment with corticosteroids (e.g. prednisolone 1-2 mg per kg/day or pulse therapy with 1 g of methylprednisolone) aims to prevent progression and rapidly stop inflammation (6). Additional mesalamine and corticosteroids may be effective in patients with bowel disease (10). In recent years, tumor necrosis alpha (TNF-α) inhibitors, such as infliximab and adalimumab, were reported to be effective for PG associated with IBD. These drugs block the biological activity of TNF-α, which effects regulatory T cells, restoring their capacity to inhibit cytokine production. The TNF-α inhibitors thus suppress the inflammatory processes that is involved in the pathogenesis of PG (11). Infliximab, a chimeric monoclonal antibody, is given by infusion at weeks 0, 2, and 6 and then every 8 weeks, usually at a dosage of 5 mg/kg. UC of patients with frequent disease relapse or those that are resistant or dependent on corticosteroids is often treated with purine antimetabolites, such as azathioprine (AZA) (10). AZA, a purine antimetabolite (2.5 mg per kg/day) is administered for its steroid-sparing effects. The response occurs after 2 to 4 weeks (6, 10). Infliximab can be combined with AZA. Patients with UC treated with infliximab plus AZA were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy (10,12).

Outcomes with the Boston Type 1 Keratoprosthesis at Instituto de Microcirugía Ocular IMO.

PubMed

Güell, Jose L; Arcos, Edilio; Gris, Oscar; Aristizabal, Diego; Pacheco, Miguel; Sanchez, Claudia L; Manero, Felicidad

2011-07-01

To report the outcomes on the Boston Type 1 Keratoprosthesis at our institution. Retrospective analysis case series. We analyzed 54 eyes of 53 patients who previously underwent Boston Type 1 Keratoprosthesis surgery at our institution from July 2006 to March 2011. Preoperative and postoperative parameters were collected and analyzed. Visual acuity and keratoprosthesis stability. Common preoperative diagnoses were penetrating keratoplasty failure in 49 eyes (90.7%), chronic keratitis in 2 eyes (3.7%), ocular cicatricial pemphigoid in 1 eye (1.85%), Stevens Johnson syndrome in 1 eye (1.85%) and corneal vascularization in 1 eye (1.85%). Additionally, 40 eyes (74%) had preoperative glaucoma, and an Ahmed valve was implanted in 55% of them. Preoperative BCVA ranged from 20/200 to light perception. At an average follow-up of 20.15 months ± 12.7 (range, 1-56), postoperative vision improved to ⩾20/200 in 18 eyes (33.3%) and ⩾20/50 in 4 eyes (7.4%). The graft retention was 96%. The Boston Type 1 keratoprosthesis is a valid option for high-risk patients. The design improvements in the Boston keratoprosthesis, as well as the daily implementation of the therapeutic methods, have notably diminished occurrence of the most serious complications, such as corneal necrosis and endophthalmitis. As such, glaucoma and its subsequent complications now stand as the most prevalent prognostic factor in the long term.

Oral and maxillofacial surgeons' role in the first successful modified osteo-odonto-keratoprosthesis performed in the United States.

PubMed

Sawatari, Yoh; Perez, Victor L; Parel, Jean-Marie; Alfonso, Eduardo; Falcinelli, Giancarlo; Falcinelli, Johnny; Marx, Robert E

2011-06-01

Corneal disease constitutes the second most common cause of blindness and often leads to corneal damage or scarring. Several corneal scarring is a complex and difficult condition for ophthalmologists to manage. In the most severe cases, the scarring is accompanied by excessive dryness and keratinization of the ocular surface. Certain etiologies, including Stevens-Johnson syndrome, cicatricial pemphigoid, Lyell's syndrome, and chemical trauma to the surface of the eye, are responsible for the most severe cases. Traditional allogeneic corneal transplantation is not effective because of the significant scarring and dryness of the eye. To allow light and images to be focused on the retina, a keratoprosthesis is required to position a lens on the surface of the eye. One of the oldest and most effective types of keratoprosthesis, the osteo-odonto-keratoprosthesis (OOKP), was first described and documented in 1963 by Strampelli and subsequently modified by Falcinelli et al. The modified OOKP (MOOKP) is a unique prosthesis consisting of a lens fabricated from a polymethylmethacrylate (PMMA) cylinder and cemented to an autogenous graft composed of tooth and bone, traditionally termed the osteo-odonto lamina. In this context, lamina refers to a thin rectangular plate of tooth and bone (Fig 1). The MOOKP involves 4 procedures performed in 3 surgical stages. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Experimental Human Cell and Tissue Models of Pemphigus

PubMed Central

van der Wier, Gerda; Pas, Hendri H.; Jonkman, Marcel F.

2010-01-01

Pemphigus is a chronic mucocutaneous autoimmune bullous disease that is characterized by loss of cell-cell contact in skin and/or mucous membranes. Past research has successfully identified desmosomes as immunological targets and has demonstrated that acantholysis is initiated through direct binding of IgG. The exact mechanisms of acantholysis, however, are still missing. Experimental model systems have contributed considerably to today's knowledge and are still a favourite tool of research. In this paper we will describe to what extent human cell and tissue models represent the in vivo situation, for example, organ cultures of human skin, keratinocyte cultures, and human skin grafted on mice and, furthermore, how suitable they are to study the pathogenesis of pemphigus. Organ cultures closely mimic the architecture of the epidermis but are less suitable to answer posed biochemical questions. Cultured keratinocyte monolayers are convenient in this respect, but their desmosomal make-up in terms of adhesion molecules does not exactly reflect the in vivo situation. Reconstituted skin is a relatively new model that approaches organ culture. In models of human skin grafted on mice, acantholysis can be studied in actual human skin but now with all the advantages of an animal model. PMID:20585596

[A CASE OF MILIARY TUBERCULOSIS ORIGINATED FROM CUTANEOUS INFECTION].

PubMed

Koda, Keigo; Enomoto, Yasunori; Omae, Minako; Akahori, Daisuke; Abe, Takefumi; Hasegawa, Hirotsugu; Matsui, Takashi; Yokomura, Koshi; Suda, Takafumi

2016-02-01

An 86-year-old woman with severe dementia had been treated with oral prednisolone at 2 mg/day for autoimmune bullous dermatosis for several years. One year ago, she referred to our hospital due to an ulcerative skin lesion over the right tibial tuberosity. The lesion was treated by an iodine-containing ointment, but did not heal. Subsequently, a new skin lesion appeared in the right popliteal fossa. One month ago, the patient had increased sputum production that was accompanied by fever, anorexia, and dyspnea; consequently, she visited our department. Chest computed tomography revealed diffuse micronodules with ground-glass attenuation. Acid-fast bacteria staining of the sputum was positive and the polymerase chain reaction detected Mycobacterium tuberculosis. In addition, the bacilli were also found in the skin lesions of the right limb. Therefore, a diagnosis of cutaneous, and miliary tuberculosis was made. Although the anti-tuberculous combination chemotherapy consisting of isoniazid, rifampicin, and ethambutol was immediately initiated, her condition did not improve. She died on day 19 of hospitalization. Drug susceptibility testing revealed no resistance to all the three drugs; hence, it was concluded that the time-delay in diagnosis of cutaneous tuberculosis lead to the progression to miliary tuberculosis and subsequent death.

Clinical Immunology Review Series: An approach to the patient with recurrent orogenital ulceration, including Behçet's syndrome

PubMed Central

Keogan, M T

2009-01-01

Patients presenting with recurrent orogenital ulcers may have complex aphthosis, Behçet's disease, secondary complex aphthosis (e.g. Reiter's syndrome, Crohn's disease, cyclical neutropenia) or non-aphthous disease (including bullous disorders, erythema multiforme, erosive lichen planus). Behçet's syndrome is a multi-system vasculitis of unknown aetiology for which there is no diagnostic test. Diagnosis is based on agreed clinical criteria that require recurrent oral ulcers and two of the following: recurrent genital ulcers, ocular inflammation, defined skin lesions and pathergy. The condition can present with a variety of symptoms, hence a high index of suspicion is necessary. The most common presentation is with recurrent mouth ulcers, often with genital ulcers; however, it may take some years before diagnostic criteria are met. All patients with idiopathic orogenital ulcers should be kept under review, with periodic focused assessment to detect evolution into Behçet's disease. There is often a delay of several years between patients fulfilling diagnostic criteria and a diagnosis being made, which may contribute to the morbidity of this condition. Despite considerable research effort, the aetiology and pathogenesis of this condition remains enigmatic. PMID:19210521

Cutaneous and systemic hypersensitivity reactions to metallic implants.

PubMed

Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C

2011-01-01

Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure. However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions remains to be fully understood. This review provides an update of the current knowledge in this field and should be valuable to health care providers who manage patients with conditions related to this field.

Fusarium dimerum Species Complex (Fusarium penzigii) Keratitis After Corneal Trauma.

PubMed

do Carmo, Anália; Costa, Esmeralda; Marques, Marco; Quadrado, Maria João; Tomé, Rui

2016-12-01

We report a case of a keratitis associated with a Fusarium penzigii-a Fusarium dimerum species complex (FDSC)-in a 81-year-old woman after a corneal trauma with a tree branch. At patient admittance, slit lamp biomicroscopy revealed an exuberant chemosis, an inferior corneal ulcer with an associated inflammatory infiltrate, a central corneal abscess, bullous keratopathy and posterior synechiae. Corneal scrapes were obtained for identification of bacteria and fungi, and the patient started antibiotic treatment on empirical basis. Few days later, the situation worsened with the development of hypopyon. By that time, Fusarium was identified in cultures obtained from corneal scrapes and the patient started topical amphotericin B 0.15 %. Upon the morphological identification of the Fusarium as a FDSC, and since there was no clinical improvement, the treatment with amphotericin B was suspended and the patient started voriconazole 10 mg/ml, eye drops, hourly and voriconazole 200 mg iv, every 12 h for 1 month. The hypopyon resolved and the inflammatory infiltrate improved, but the abscess persisted at the last follow-up visit. The molecular identification revealed that the FDSC was a F. penzigii.

Bed Bugs: Clinical Relevance and Control Options

PubMed Central

Dwyer, Dominic E.; Peñas, Pablo F.; Russell, Richard C.

2012-01-01

Summary: Since the late 1990s, bed bugs of the species Cimex lectularius and Cimex hemipterus have undergone a worldwide resurgence. These bed bugs are blood-sucking insects that readily bite humans. Cutaneous reactions may occur and can start out as small macular lesions that can develop into distinctive wheals of around 5 cm in diameter, which are accompanied by intense itching. Occasionally, bullous eruptions may result. If bed bugs are numerous, the patient can present with widespread urticaria or eythematous rashes. Often, bites occur in lines along the limbs. Over 40 pathogens have been detected in bed bugs, but there is no definitive evidence that they transmit any disease-causing organisms to humans. Anemia may result when bed bugs are numerous, and their allergens can trigger asthmatic reactions. The misuse of chemicals and other technologies for controlling bed bugs has the potential to have a deleterious impact on human health, while the insect itself can be the cause of significant psychological trauma. The control of bed bugs is challenging and should encompass a multidisciplinary approach utilizing nonchemical means of control and the judicious use of insecticides. For accommodation providers, risk management procedures should be implemented to reduce the potential of bed bug infestations. PMID:22232375

Boric acid ingestion clinically mimicking toxic epidermal necrolysis.

PubMed

Webb, David V; Stowman, Anne M; Patterson, James W

2013-11-01

The ingestion of large amounts of boric acid, a component of household insecticides, is a rare occurrence, characterized by a diffuse desquamative skin eruption, neutropenia, thrombocytopenia, delirium, acute renal failure and prolonged ileus. A 56-year-old male with a history of multiple previous suicide attempts was witnessed ingesting household roach killer and 4 days later presented to the hospital with lethargy, stiffness and a diffuse erythematous and desquamative eruption with bullous formation. He subsequently developed erythema of both palms as well as alopecia totalis. Histopathology from a right arm shave biopsy revealed a mostly intact epidermis with subtle vacuolar alteration of the basal layer, scattered intraepidermal apoptotic keratinocytes, parakeratosis with alternating layers of orthokeratosis and considerable superficial exfoliation; accompanying dermal changes included vasodilatation and mild perivascular inflammation. This report describes the cutaneous and systemic complications in a rare case of boric acid ingestion. There is little published material on the symptoms and histopathology following boric acid ingestion, but knowledge of this entity is important, both to differentiate it from other causes of desquamative skin rashes and to allow the initiation of appropriate clinical care. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An unusual etiology in cold injury: Liquefied petroleum gas.

PubMed

Kapı, Emin; Bozkurt, Mehmet; Taylan Filinte, Gaye; Kuvat, Samet Vasfi; Alioğlu, Celal

2017-05-01

Cold injury is a condition that causes reversible and irreversible damage when tissues are exposed to cold. This injury occurs due to various etiologies, and the most commonly observed ones include contact with liquefied petroleum gas (LPG) used in households, vehicles, and industry. LPG is a type of gas stored in liquid state under high pressure within cylinders. LPG contains a mixture of propane and butane gases. Direct contact of these gases with the tissues has the potential to cause metabolic, toxic, and respiratory damage. In this study, we present the cases of four patients with cold injury in the face and upper extremity caused by a pressurized jet stream of liquid gas that escaped out of the valves of the LPG cylinders. The patients had bullous lesions in the upper extremities and the face and second- and third-degree cold injuries with fibrotic and necrotic areas. The superficial defects secondarily healed with minimal scarring, while the necrotic finger had to be amputated. Cold injury on the skin caused by high-pressure jet streams of liquid gas as in our study is a rare occurrence. Our patients are important cases due to the rare etiology of cold injury.

Incidence, clinical features and diagnosis of cicatrising conjunctivitis in Australia and New Zealand.

PubMed

Bobba, Samantha; Devlin, Connor; Di Girolamo, Nick; Wakefield, Denis; McCluskey, Peter; Chan, Elsie; Daniell, Mark; Watson, Stephanie

2018-06-19

This study aimed to determine the incidence, clinical features and management of cicatrising conjunctivitis in Australia and New Zealand, also enabling comparison with data from the United Kingdom. A prospective surveillance study was conducted over 17 months via the Australian and New Zealand Ophthalmic Surveillance Unit with a one-year follow-up period. Practicing ophthalmologists on the Surveillance Unit's database were asked to report recently diagnosed cases of cicatrising conjunctivitis on a monthly basis. Initial and follow-up questionnaires were sent to ophthalmologists who had reported positive cases to obtain demographic and clinical data. The minimum incidence of cicatrising conjunctivitis was calculated based on cases reported during the study period and from population data. During the 17-month study period (December 2011-April 2013), 56 cases of cicatrising conjunctivitis were reported. Data was obtained for 35 cases (62%) with a mean age of 74 years (range, 28-94 years). The most common aetiologies were ocular mucus membrane pemphigoid (n = 18 cases, 51.4%), Stevens-Johnson Syndrome (n = 3, 8.6%) and graft versus host disease (n = 3, 8.6%). The minimum incidence of cicatrising conjunctivitis in Australia and New Zealand was 1.5 per million, comparable to incidence data from the United Kingdom. This study is the first to prospectively record the incidence of cicatrising conjunctivitis in Australia and New Zealand and the second worldwide. It provides novel data on demographics and management of cicatrising conjunctivitis, as reported by treating ophthalmologists.

Osteo-odonto-keratoprosthesis in Japan.

PubMed

Fukuda, Masahiko; Hamada, Suguru; Liu, Christopher; Shimomura, Yoshikazu

2008-09-01

Osteo-odonto-keratoprosthesis (OOKP) is a keratoprosthesis technique in which the patient's own tooth root is used to support an optical cylinder. It was invented by Strampelli in 1963 and modified and established by Falcinelli about 10 years later. This method is particularly useful for restoring sight in end-stage Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP). We started performing OOKP surgery in June 2003 supported by Dr Christopher Liu of Sussex Eye Hospital, Brighton, UK. Till now, we have performed 4 OOKP surgeries for end-stage SJS and OCP. We modified the original method by using artificial buccal mucous membranes to the bone and buccal mucous membrane defects for better wound healing. Case 1 was a 49-year-old woman (SJS), and the corrected visual acuity was 0.5 in 4 years 8 months. Case 2 was a 68-year-old woman (SJS), and the corrected visual acuity was 0.04 in 3 years 10 months. Case 3 was a 63-year-old man (SJS), and the corrected visual acuity was 0.1 in 3 years 2 months. Case 4 was a 71-year-old woman (OCP), and the corrected visual acuity was 0.04 in 1 year 3 months. Despite some minor optical cylinder troubles such as MRSA colonization, tilting, and buccal mucous coverage, their visual acuities were stable without any serious complications. It was demonstrated that OOKP is useful for visual rehabilitation and durable with minimum eye care for severe ocular surface diseases.

Towards a synthetic osteo-odonto-keratoprosthesis.

PubMed

Viitala, Reeta; Franklin, Valerie; Green, David; Liu, Christopher; Lloyd, Andrew; Tighe, Brian

2009-01-01

Osteo-odonto-keratoprostheses (OOKP) is a unique form of keratoprosthesis involving surgical removal of a tooth root and surrounding bone from the patient which are then used to construct an osteo-odonto lamina into which an optical cylinder is cemented. The OOKP procedure is successful and capable of withstanding the very hostile ocular environments found in severe Stevens-Johnson syndrome, pemphigoid, chemical burns, trachoma and multiple corneal graft failure. The existing procedure is complex and time consuming in terms of operative time, and additionally involves sacrifice of the oral structures. This paper discusses the rational search for a "synthetic" analogue of the dental lamina, capable of mimicking those features of the natural system that are responsible for the success of OOKP. In this study the degradation of selected commercial and natural bioceramics was tested in vitro using a purpose-designed resorption assay. Degradation rate was compared with tooth and bone, which are currently used in OOKP lamina. At normal physiological pH the degradation of bioceramics was equivalent to tooth and bone; however, at pH 6.5-5.0, associated with infectious and inflamed tissues, the bioceramics degrade more rapidly. At lower pH the degradation rate decreased in the following order: calcium carbonate corals>biphasic calcium phosphates>hydroxyapatite. Porosity did not significantly influence these degradation rates. Such degradation is likely to compromise the stability and viability of the synthetic OOKP. Consequently more chemically stable materials are required that are optimized for the surrounding ocular environment.

[Osteo-odonto-keratoprosthesis. A summary of 6 years surgical experience].

PubMed

Hille, K; Landau, H; Ruprecht, K W

2002-02-01

In patients with severe corneal scarring and vascularisation, corneal grafts have a high risk of failure. In those patients an osteo-odonto-keratoprosthesis (OOKP) can be performed. We performed OOKP in eight patients in all with ocular pemphigoid, severe alkali burns, or repulsion of a corneal graft. Each of the patients had finger-counting visual acuity or less. The OOKP consisted of a PMMA cylinder 8 mm long, with a diameter of 3-4 mm, and from a root of the patient's tooth. This was implanted in the cornea and covered with buccal mucosa. The medium follow-up was 3 years. The implants are now well incorporated. The best visual acuity was between 0.6 and 0.9 in four patients with intact retinas. In the remaining patients, visual acuity was dependent on the posterior segment findings. The visual field was centred. Five of the eight patients had vitreous bleeding after the operation that was spontaneously absorbed. Revision of the mucous coverage was necessary in four patients, and one of them had a severe inflammation with partial absorption of the bone and tooth implant. One patient developed a secondary angle-closure glaucoma and was treated successfully by implantation of an Ahmed valve. Two patients developed membranes behind the cylinder that were successfully removed. There was no loss of any prosthesis during follow-up. In impasse in severe corneal scars, the osteo-odonto-keratoprosthesis is still indicated and shows good results in visual rehabilitation of patients.

An epidemiological study of immune-mediated skin diseases affecting the oral cavity.

PubMed

Carvalho, Cyntia Helena Pereira de; Santos, Bruna Rafaela Martins dos; Vieira, Camila de Castro; Lima, Emeline das Neves de Araújo; Santos, Pedro Paulo de Andrade; Freitas, Roseana de Almeida

2011-01-01

Immune-mediated skin diseases encompass a variety of pathologies that present in different forms in the body. The objective of this study was to establish the prevalence of the principal immune-mediated skin diseases affecting the oral cavity. A total of 10,292 histopathology reports stored in the archives of the Anatomical Pathology Laboratory, Department of Oral Pathology, Federal University of Rio Grande do Norte, covering the period from 1988 to 2009, were evaluated. For the cases diagnosed with some type of disease relevant to the study, clinical data such as the gender, age and ethnicity of the patient, the anatomical site of the disease and its symptomatology were collected. Of all the cases registered at the above-mentioned service, 82 (0.8%) corresponded to immune-mediated skin diseases with symptoms affecting the oral cavity. The diseases found in this study were: oral lichen planus, pemphigus vulgaris and benign mucous membrane pemphigoid. Oral lichen planus was the most common lesion, comprising 68.05% of the cases analyzed. Of these cases, 64.3% were women and the cheek mucosa was the anatomical site most commonly affected (46.8%). Immune-mediated skin diseases affecting the oral cavity continue to be rare, the prevalence found in this study being similar to that reported for the majority of regions worldwide. Nevertheless, early diagnosis is indispensable in the treatment of these diseases, bearing in mind that systemic involvement is possible in these patients.

A review on botanicals with wound healing activity for pemphigus vulgaris: perspective of traditional Persian medicine and conventional medicine

PubMed Central

Atarzadeh, Fatemeh; Jaladat, Amir Mohammad; Daneshfard, Babak; Dastgheib, Ladan; Kamalinejad, Mohammad; Amin, Gholamreza

2017-01-01

Objective: As a rare autoimmune disease, pemphigus vulgaris has a poor prognosis especially in lack of proper medical support. This blistering disease involves both the skin and mucus membranes. The challenge is improving the healing process of skin lesions of which, superimposed infections are among the main causes of the disease mortality. Accordingly, we aimed to assess the treatment options suggested by traditional Persian medicine (TPM) and compare them with current findings. Materials and Methods: We studied the main clinical and pharmaceutical textbooks of TPM (Kitāb al-hāwīfī al-tibb, the Canon of Medicine, Eksir-e-Aazam, Tuhfat al-mu'minīn, Makhzan al-adviyah (focusing on the skin chapter and respective herbal remedies for the inflamed skin and ulcers. Additionally, scientific databases such as PubMed, Science direct, Scopus, and Google Scholar were searched for the current pharmacological evidence. In the studied books, the term “hot ulcers” was found close to what is known as “Pemphigus vulgaris”. Results: Reported medicinal herbs possess anti-inflammatory, antioxidant, wound healing, and antibacterial activities reported by recent studies. Therefore, they could be introduced as novel natural remedies for pemphigoid wounds. Conclusion: Taken as a whole, the review of traditional remedies for hot ulcers in Persian medical and pharmaceutical literature may open a new window toward developing new topical treatments for this disease. PMID:29299431

Clinical optical coherence tomography combined with multiphoton tomography for evaluation of several skin disorders

NASA Astrophysics Data System (ADS)

König, Karsten; Speicher, Marco; Bückle, Rainer; Reckfort, Julia; McKenzie, Gordon; Welzel, Julia; Koehler, Martin J.; Elsner, Peter; Kaatz, Martin

2010-02-01

The first clinical trial of optical coherence tomography (OCT) combined with multiphoton tomography (MPT) and dermoscopy is reported. State-of-the-art (i) OCT systems for dermatology (e.g. multibeam swept source OCT), (ii) the femtosecond laser multiphoton tomograph DermaInspectTM, and (iii) digital dermoscopes were applied to 47 patients with a diversity of skin diseases and disorders such as skin cancer, psoriasis, hemangioma, connective tissue diseases, pigmented lesions, and autoimmune bullous skin diseases. Dermoscopy, also called 'epiluminescent microscopy', provides two-dimensional color images of the skin surface. OCT imaging is based on the detection of optical reflections within the tissue measured interferometrically whereas nonlinear excitation of endogenous fluorophores and the second harmonic generation are the bases of MPT images. OCT cross sectional "wide field" image provides a typical field of view of 5 x 2 mm2 and offers fast information on the depth and the volume of the investigated lesion. In comparison, multiphoton tomography presents 0.36 x 0.36 mm2 horizontal or diagonal sections of the region of interest within seconds with submicron resolution and down to a tissue depth of 200 μm. The combination of OCT and MPT provides a synergistic optical imaging modality for early detection of skin cancer and other skin diseases.

Importance of exfoliatin toxin A production by Staphylococcus aureus strains isolated from clustered epidemics of neonatal pustulosis.

PubMed Central

Kaplan, M H; Chmel, H; Hsieh, H C; Stephens, A; Brinsko, V

1986-01-01

Clustered epidemics of pustulosis due to Staphylococcus aureus occurred in two geographically distant newborn nurseries. In nurseries A and B an attack rate of pustulosis of 0.8 and 2.0 cases per 100 live births occurred, respectively. Experimental phage type 1046/1116 belonging to phage group II dominated clustered epidemics in nursery A, while group II phage type 3A/3C/55/71 and 3A/3C/55 occurred in nursery B. Other group II strains also occasionally produced clustered epidemics. These epidemic strains were found to be making heat-stable dermal exfoliatin toxin A (ETA) which had a pI of 6.8 and a molecular weight of 32,000 and 33,000. ETA-bearing strains did not make bacteriocin. Children infected with ETA-producing strains developed extensive bullous pustulosis. Surveillance cultures of personnel revealed an ETA-bearing strain in only one person. This strain was not the same phage type as the epidemic cluster. In contrast, ETA-bearing epidemic strains were found in the inanimate environment of both nurseries. ETA protein acts as an important virulence factor in the production of neonatal pustulosis infection and appears to be linked with the ability of S. aureus organisms to stick to the inanimate environment. Images PMID:3700612

Genotyping of HLA-I and HLA-II alleles in Chinese patients with paraneoplastic pemphigus.

PubMed

Liu, Q; Bu, D-F; Li, D; Zhu, X-J

2008-03-01

Class I and class II HLA genes are thought to play a role in the immunopathogenesis of bullous dermatoses such as pemphigus vulgaris and pemphigus foliaceus, but we know little about the genetic background of paraneoplastic pemphigus (PNP) in Chinese patients. To identify class I and class II HLA alleles by genotyping in Chinese patients with PNP, and to find out the possible association between HLA alleles and disease susceptibility. Nineteen Chinese patients with PNP were enrolled in this study. HLA-A, B, C, DRB1 and DQB1 alleles were typed by polymerase chain reaction and a colour-coded sequence-specific oligonucleotide probes method. The frequencies of HLA-B*4002/B*4004, B*51, B*52, Cw*14, DQB1*0301, DRB1*08 and DRB1*11 were relatively prevalent in Chinese Han patients with PNP in comparison with normal controls. After correction for multiple comparisons, Cw*14 remained statistically significant, and the other alleles were unremarkable in these patients. The genetic background predisposing to PNP may be different in patients from various races and areas. HLA-Cw*14 may be the predisposing allele to PNP in Chinese patients, which is different from the predisposing allele in French patients with PNP and the alleles predisposing to pemphigus vulgaris and pemphigus foliaceus.

Neutrophilic Skin Lesions in Autoimmune Connective Tissue Diseases

PubMed Central

Hau, Estelle; Vignon Pennamen, Marie-Dominique; Battistella, Maxime; Saussine, Anne; Bergis, Maud; Cavelier-Balloy, Benedicte; Janier, Michel; Cordoliani, Florence; Bagot, Martine; Rybojad, Michel; Bouaziz, Jean-David

2014-01-01

Abstract The pathophysiology of neutrophilic dermatoses (NDs) and autoimmune connective tissue diseases (AICTDs) is incompletely understood. The association between NDs and AICTDs is rare; recently, however, a distinctive subset of cutaneous lupus erythematosus (LE, the prototypical AICTD) with neutrophilic histological features has been proposed to be included in the spectrum of lupus. The aim of our study was to test the validity of such a classification. We conducted a monocentric retrospective study of 7028 AICTDs patients. Among these 7028 patients, a skin biopsy was performed in 932 cases with mainly neutrophilic infiltrate on histology in 9 cases. Combining our 9 cases and an exhaustive literature review, pyoderma gangrenosum, Sweet syndrome (n = 49), Sweet-like ND (n = 13), neutrophilic urticarial dermatosis (n = 6), palisaded neutrophilic granulomatous dermatitis (n = 12), and histiocytoid neutrophilic dermatitis (n = 2) were likely to occur both in AICTDs and autoinflammatory diseases. Other NDs were specifically encountered in AICTDs: bullous LE (n = 71), amicrobial pustulosis of the folds (n = 28), autoimmunity-related ND (n = 24), ND resembling erythema gyratum repens (n = 1), and neutrophilic annular erythema (n = 1). The improvement of AICTDS neutrophilic lesions under neutrophil targeting therapy suggests possible common physiopathological pathways between NDs and AICTDs. PMID:25546688

Autoimmunity-related neutrophilic dermatosis: a newly described entity that is not exclusive of systemic lupus erythematosus.

PubMed

Saeb-Lima, Marcela; Charli-Joseph, Yann; Rodríguez-Acosta, Elva Dalia; Domínguez-Cherit, Judith

2013-08-01

Neutrophilic dermatoses have long been known to be associated with autoinmune systemic diseases. Recently, a small number of cases of a disorder distinct from Sweet syndrome or bullous lupus erythematosus (LE) have been described as specifically related to systemic LE under diverse terms, including nonbullous neutrophilic dermatosis, nonbullous neutrophilic LE, and Sweet-like neutrophilic dermatosis. We describe 7 patients that developed urticarial lesions in the context of a known or concurrently diagnosed autoimmune connective tissue disease. Of a total of 7 patients, 6 were afflicted by systemic LE and 1 by rheumatoid arthritis and secondary Sjögren syndrome. Histological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, vacuolar alteration along the dermal-edidermal junction, and no vasculitis. Most patients had active systemic disease at the time of the cutaneous eruption. Skin lesions resolved rapidly after the administration of immunomodulating agents. In conclusion, we provide additional evidence of the existence of a recently defined nonbullous neutrophilic dermatosis in the context of autoimmune connective tissue diseases and propose the term autoimmunity-related neutrophilic dermatosis as an appropriate designation. Furthermore, we believe that this entity should prompt physicians to screen the presence of an active systemic disorder in afflicted patients.

Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases.

PubMed

König, Karsten; Speicher, Marco; Bückle, Rainer; Reckfort, Julia; McKenzie, Gordon; Welzel, Julia; Koehler, Martin J; Elsner, Peter; Kaatz, Martin

2009-07-01

We report on the first clinical study based on optical coherence tomography (OCT) in combination with multiphoton tomography (MPT) and dermoscopy. 47 patients with a variety of skin diseases and disorders such as skin cancer, psoriasis, hemangioma, connective tissue diseases, pigmented lesions, and autoimmune bullous skin diseases have been investigated with (i) state-of-the-art OCT systems for dermatology including multibeam swept source OCT, (ii) the femtosecond laser multiphoton tomograph, and (iii) dermoscopes. Dermoscopy provides two-dimensional color images of the skin surface. OCT images reflect modifications of the intratissue refractive index whereas MPT is based on nonlinear excitation of endogenous fluorophores and second harmonic generation. A stack of cross-sectional OCT "wide field" images with a typical field of view of 5 x 2 mm(2) gave fast information on the depth and the volume of the lesion. Multiphoton tomography provided 0.36 x 0.36 mm(2) horizontal/diagonal optical sections within seconds of a particular region of interest with superior submicron resolution down to a tissue depth of 200 mum. The combination of OCT and MPT provides a unique powerful optical imaging modality for early detection of skin cancer and other skin diseases as well as for the evaluation of the efficiency of treatments.

[Selective left mainstem bronchial intubation in the neonatal intensive care unit].

PubMed

Ho, Anthony M H; Flavin, Michael P; Fleming, Melinda L; Mizubuti, Glenio Bitencourt

Selective neonatal left mainstem bronchial intubation to treat right lung disease is typically achieved with elaborate maneuvers, instrumentation and devices. This is often attributed to bronchial geometry which favors right mainstem entry of an endotracheal tube deliberately advanced beyond the carina. A neonate with severe bullous emphysema affecting the right lung required urgent non-ventilation of that lung. We achieved left mainstem bronchial intubation by turning the endotracheal tube 180° such that the Murphy's eye faced the left instead of the right, and simulated a left-handed intubation by slightly orientating the endotracheal tube such that its concavity faced the left instead of the right as in a conventional right-handed intubation. Urgent intubation of the left mainstem bronchus with an endotracheal tube can be easily achieved by recognizing that it is the position of the endotracheal tube tip and the direction of its concavity that are the chief determinants of which bronchus an endotracheal tube goes when advanced. This is important in critically ill neonates as the margin of safety and time window are small, and the absence of double-lumen tubes. Use of fiberoptic bronchoscope and blockers should be reserved as backup plans. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Pure cutaneous lupus erythematosus in a population of African descent in French Guiana: a retrospective population-based description.

PubMed

Deligny, C; Marie, D Sainte; Clyti, E; Arfi, S; Couppié, P

2012-11-01

The objective of this study was to examine the characteristics of cutaneous lupus erythematosus, excluding systemic lupus erythematosus (SLE), in patients of African descent. Indeed, since the description of subacute cutaneous lupus erythematosus (SCLE), which had been included in chronic cutaneous lupus erythematosus (CCLE), there has been no description of the disease in black patients. In 2000, we performed a retrospective epidemiological study by querying multiple sources to identify all patients with lupus in French Guiana--a part of France in South America having western living conditions, free healthcare and 157,000 inhabitants, most of whom are of African origin. We found 45 patients with pure cutaneous lupus, which included CCLE (mostly discoid), SCLE and bullous lupus. The disease characteristics of these patients exhibited few differences compared with those of the Caucasian patients cited in the literature. However, the age of onset for our patients of African descent was younger than that of Caucasian patients. In contrast to the race-related differences reported for SLE, we found no major differences in terms of demographic, clinical and biological presentation between this cohort of pure cutaneous lupus erythematosus patients of African origin and Caucasian patients with similar forms of lupus.

Trauma-induced pemphigus: a case series of 36 patients.

PubMed

Daneshpazhooh, Maryam; Fatehnejad, Mina; Rahbar, Ziba; Balighi, Kamran; Ghandi, Narges; Ghiasi, Maryam; Abedini, Robabeh; Lajevardi, Vahideh; Chams-Davatchi, Cheyda

2016-02-01

Pemphigus is a group of autoimmune diseases characterized by intraepidermal acantholytic blisters. Isomorphic responses, or Koebner phenomenon (KP), defined as the appearance of typical lesions of a disease following trauma are rarely reported in pemphigus. Our aim was to present patients who developed new pemphigus lesions as a result of skin trauma. The medical files of pemphigus patients from the Autoimmune Bullous Diseases Research Center, who had a history of trauma before the onset or flare of their disease, between 1999 and 2013 were reviewed. Thirty-six pemphigus vulgaris (PV) patients had a history of trauma. Thirteen patients developed new-onset PV and the other 23 had previously been diagnosed with PV. Pemphigus lesions developed most often following major surgeries including abdominal, orthopedic, and chest surgeries as well as dental procedures, blunt physical trauma, and skin surgeries. Moreover, post-cataract laser surgery, burns, radiation therapy, and physiotherapy were also shown to induce pemphigus. Mean time between trauma and lesions was 4.7 weeks for recurrent PV and 15.0 weeks for new-onset PV. Unnecessary surgery and blunt trauma should be avoided in pemphigus patients. Furthermore, posttraumatic pemphigus should be suspected in poorly healing surgical wounds and confirmatory biopsies are mandatory. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Occupational toxic epidermal necrolysis associated with dalbergia cochinchinensis: a retrospective comparative study of eight cases in China.

PubMed

Yang, Yongsheng; Zhang, Zhen; Lu, Xiaonian; Zhu, Xiaohua; Huang, Qiong; Liang, Jun; Xu, Jinhua

2015-12-01

Occupational toxic epidermal necrolysis (TEN) related to Dalbergia cochinchinensis has seldom been reported in the past. Its clinical characteristic needs to be investigated. This study reports eight cases of such disease in China. Eight patients with occupational TEN admitted from 2003 to 2012 were retrospectively analyzed and compared with 15 patients admitted with TEN caused by drugs as controls. Patients all received combination therapy of corticosteroid and intravenous immunoglobulin. The times for bullous ceasing, tapering of corticosteroid, and total hospitalization were compared between the two groups of patients. SCORTEN, a severity-of-illness scoring system for TEN prognosis, was applied to evaluate clinical outcome. The three time measurements in occupational TEN were longer than those in control, and the differences were statistically significant (P = 0.0023, 0.026, 0.0017), which means the total dose of corticosteroid needed in occupational TEN was higher than that in the control. There were no deaths in the two groups, although expected deaths were 0.612 and 0.836, respectively. Occupational TEN has a longer progression than TEN caused by drugs, and there is more difficulty in its treatment. Clinicians should pay attention to this disease. However, its mechanism and target therapy remain unclear. © 2015 The International Society of Dermatology.

Radiology compared with xenon—133 scanning and bronchoscopic lobar sampling as methods for assessing regional lung function in patients with emphysema

PubMed Central

Barter, C. E.; Hugh-Jones, P.; Laws, J. W.; Crosbie, W. A.

1973-01-01

Regional lung function was assessed by radiographic methods, by regional function studies using xenon-133 scans, and by lobar sampling with a mass spectrometer flow-meter at bronchoscopy in 12 patients who subsequently had bullae resected at operation. The information given by these three methods of regional assessment was subsequently compared with the findings at operation. When only one lobe was abnormal on the radiographs, these alone were adequate to locate the major site of the emphysema and the regional tests gave relatively little extra information. The xenon scan was sometimes helpful in assessing the state of the remaining lung, but this information could be deduced from the radiographs and overall lung function tests, especially the carbon monoxide transfer and mechanical measurements. Bronchoscopic sampling was helpful in determining whether the affected lobe was acting as a ventilated dead-space. When more than one lobe was affected the regional function tests supplemented the radiographs in defining the site of bullous change as well as locating dead space. Xenon scans, although widely employed for such preoperative assessments, added little to the topographical information obtained by careful radiology. The combination of radiology, lobar sampling, and overall function tests is recommended for assessing which emphysematous patients are likely to benefit from surgery. Images PMID:4685209

Telemedicine in wound care.

PubMed

Chanussot-Deprez, Caroline; Contreras-Ruiz, José

2008-12-01

Telemedical wound care is one of the applications of teledermatology. We present our experience using telemedicine in the successful assessment and treatment of three patients with hard-to-heal ulcers. Three patients were seen at the PEMEX General Hospital in Veracruz, Mexico. The first patient was a 53-year-old man with hypertension, morbid obesity, chronic venous insufficiency, recurrent erysipelas, leg ulcers and lymphoedema. There was one ulcer on his left lower leg (20 x 10 cm) and one on his right leg (9 x 7 cm). The second patient was a 73-year-old woman with class III obesity and ulcers in her right leg, secondary to surgical debridement of bullous erysipelas. The third patient was a 51-year-old female with rheumatoid arthritis with one ulcer on each leg and chronic lymphostasis. Photographs with a digital camera were taken and sent weekly via email to a wound care specialist in Mexico City. The photographs allowed the expert to diagnose and evaluate the chronic wounds periodically. In the present cases, telemedicine allowed us to have a rapid evaluation, diagnosis and treatment. The images were of enough quality to be useful and small enough to be sent via regular email to the remote physician who immediately gave his feedback. The expert was confident to give therapeutic recommendations in this way, and we considered this method to be very cost-effective, saving the patient and the health care system, especially in transportation.

Clinical combination of multiphoton tomography and high frequency ultrasound imaging for evaluation of skin diseases

NASA Astrophysics Data System (ADS)

König, K.; Speicher, M.; Koehler, M. J.; Scharenberg, R.; Elsner, P.; Kaatz, M.

2010-02-01

For the first time, high frequency ultrasound imaging, multiphoton tomography, and dermoscopy were combined in a clinical study. Different dermatoses such as benign and malign skin cancers, connective tissue diseases, inflammatory skin diseases and autoimmune bullous skin diseases have been investigated with (i) state-of-the-art and highly sophisticated ultrasound systems for dermatology, (ii) the femtosecond-laser multiphoton tomograph DermaInspectTM and (iii) dermoscopes. Dermoscopy provides two-dimensional color imaging of the skin surface with a magnification up to 70x. Ultrasound images are generated from reflections of the emitted ultrasound signal, based on inhomogeneities of the tissue. These echoes are converted to electrical signals. Depending on the ultrasound frequency the penetration depth varies from about 1 mm to 16 mm in dermatological application. The 100-MHz-ultrasound system provided an axial resolution down to 16 μm and a lateral resolution down to 32 μm. In contrast to the wide-field ultrasound images, multiphoton tomography provided horizontal optical sections of 0.36×0.36 mm2 down to 200 μm tissue depth with submicron resolution. The autofluorescence of mitochondrial coenzymes, melanin, and elastin as well as the secondharmonic- generation signal of the collagen network were imaged. The combination of ultrasound and multiphoton tomography provides a novel opportunity for diagnostics of skin disorders.

Epidemiological investigation of nosocomial outbreak of staphylococcal skin diseases in neonatal ward.

PubMed

Kurlenda, J; Grinholc, M; Krzysztoń-Russjan, J; Wiśniewska, K

2009-05-01

During a 1-month period, eight neonates developed staphylococcal skin disease diagnosed as a bullous impetigo in the maternity unit of the Provincial Hospital in Gdansk. An epidemiological investigation based on phenotyping and genotyping methods was performed. All neonates involved in the outbreak, their mothers and 15 staff members were screened for carriage of Staphylococcus aureus by nasal swabs. Isolated strains were compared with strains cultured from affected skin and purulent conjunctiva of infected newborns. Isolates were analyzed for the presence of the etA and etB genes using polymerase chain reaction and genotyped by pulsed-field gel electrophoresis (PFGE) and coa gene polymorphism. The analyzed S. aureus strains were methicillin-sensitive and could be divided into two groups according to antibiotyping, phage typing, coa polymorphism and PFGE pattern. The first group consisted of etA and etB negative strains, and the second one involved only the etB positive ones. Our results have shown that there were two different clusters of infection caused by two populations of S. aureus strains. Among the 15 medical staff members screened we have found seven carriers. However, phage typing revealed that distinct strains unrelated to the outbreak isolates were carried. Although we have not been able to establish the source of bacteria involved in the outbreak, our results suggest that for both groups, mothers could be the source of the infecting strains.

[Ulcerative colitis: exceptional consequence after rituximab therapy].

PubMed

Sekkach, Y; Hammi, S; Elqatni, M; Fatihi, J; Badaoui, M; Elomri, N; Mekouar, F; Smaali, J; Jira, M; Amezyane, T; Abouzahir, A; Ghafir, D

2011-09-01

Possible adverse complications related to rituximab (RTX) are low, some of which are extremely rare. The authors describe one situation visibly waning exceptional treatment with RTX for SLE refractory to conventional therapies. The authors report a patient of 34 years followed for months for an illness in its bullous lupus, with cutaneous, articular, hematologic and immunologic. Given a corticosteroid resistance, several therapeutic background based hydroxychloroquine, cyclophosphamide and methotrexate, were initiated without any improvement. Immunomodulatory therapy type RTX was introduced to this form refractory at a rate of 375mg/m(2)/week. The waning of the second infusion, the patient presented a sudden intense abdominal pain syndrome, revealing an acute catarrhal appendicitis. At distance from the appendectomy, the consequences of which were favorable, treatment with RTX was resumed. In the aftermath of the third infusion, the patient presented in table tract marked by profuse watery diarrhea whose explorations reveal a morphological endoscopic appearance of erythematous, ulcerative colitis, reversible upon discontinuation of treatment. Histological data revealed important infiltrates composed mainly of CD8T lymphocytes. Gastrointestinal immunological consequences to the requirements of the targeted therapies deserved very careful and rigorous monitoring. However, at the slightest sign of digestive, a detailed morphological exploration is essential, to avoid in particular surgical emergency, evolution without treatment could engage in short-term vital prognosis. 2011 Elsevier Masson SAS. All rights reserved.

Mefloquine adverse effects with atypical facial lesions in an overweight patient.

PubMed

Descloux, Elodie; De Monbrison, Frédérique; Basselin, Cécile; Vial, Thierry; Peyron, François

2010-09-01

The recommended dosage of mefloquine to treat Plasmodium falciparum infection is 25 mg/kg, with no recommendation for dosage exceeding 1500 mg. We describe an original case of adverse reaction to mefloquine in an overweight patient. Case report. A 32-year-old woman weighing 139 kg presented with uncomplicated P. falciparum infection after returning from Cameroon. She received 3250 mg of mefloquine (i.e. 23 mg/kg) administered in four doses. On day 2, she developed neuropsychiatric disorders and facial lesions. Nasal mucocutaneous vesicles and bullae, depressive mood, mild thrombocytopenia and hepatic cytolysis were evidenced. Parasitemia was negative. Recovery was complete on day 17. High mefloquine serum levels were measured (8.030 mg/L on day 3, 6.880 mg/L on day 8, and 3.370 mg/L on day 17). The causal relationship between mefloquine and the occurrence of these adverse effects is probable. However, as no viral or bacteriological investigations were performed, the drug responsibility remains uncertain. Mefloquine-induced bullous and facial lesions reversible upon drug withdrawal have already been described. The associated neuropsychiatric symptoms were strongly suggestive of mefloquine adverse effects, as such events are more frequently observed in cases of overdosage. Our case emphasizes the difficulties of dosage adaptation in overweight patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

MACULAR HOLE FORMATION FOLLOWED BY SPONTANEOUS CLOSURE AFTER PNEUMATIC RETINOPEXY IN A PATIENT WITH DIABETIC MACULAR EDEMA.

PubMed

Cohen, Michael N; Baumal, Caroline R

2018-05-10

To report early formation and spontaneous closure of a full-thickness macular hole that developed after successful pneumatic retinopexy in a patient who had been undergoing treatment for diabetic macular edema. Case report of a 68-year-old man with bilateral nonproliferative diabetic retinopathy who was currently undergoing anti-vascular endothelial growth factor treatment for bilateral diabetic macular edema. On presentation, visual acuity was 20/200 in the left eye, and examination revealed a bullous, macula-off retinal detachment with a single horseshoe tear at 12 o'clock in the left eye. Pneumatic retinopexy was performed followed by laser augmentation 3 days later. Three weeks postoperatively, he returned with visual acuity of 20/50 and a full-thickness macular hole in the left eye. Although he elected for initial observation, he returned 2 weeks later with visual acuity of 20/50 in both eyes and a retinal detachment with a single break at 10 o'clock in the right eye. The macular hole in the left eye had spontaneously resolved. Pneumatic retinopexy was performed to the right eye. Over 1 year after bilateral pneumatic retinopexy, his retina remains without recurrence of a macular hole in the left eye. In the early postoperative period after pneumatic retinopexy to repair a retinal detachment, a macular hole can form and spontaneously close.

[Descemet's stripping automated endothelial keratoplasty (DEAEK). Systematic review of clinical-effectiveness and safety].

PubMed

Paz-Valiñas, L; de la Fuente-Cid, R; de Rojas-Silva, M V; López-Rodríguez, I; López-García, M

2015-04-01

To conduct a systematic review of the efficacy/effectiveness, safety and cost of Descemet's stripping automated endothelial keratoplasty (DSAEK) technique in patients with corneal endothelial failure. Comprehensive literature search conducted in the main biomedical databases from January-May 2012. Following a critical perusal of the total of 485 abstracts retrieved, 16 case series and one economic evaluation study were included. Corrected distance visual acuity and uncorrected distance visual acuity improved after treatment with DSAEK, attaining values of 0.6 to 0.8 and 0.5 respectively. The degree of post-DSAEK astigmatism was not significant with respect to baseline values. The main complications were graft dislocation-detachment (1.5-23%), primary failure (0-12%) and endothelial rejection (0.8-8.5%). In Fuchs' dystrophy and bullous keratopathy, data on the effectiveness of DSAEK indicate post-intervention improvement in uncorrected and corrected distance visual acuity. Astigmatism arising after DSAEK was not significant. The most significant post-DSAEK complications are linked to the viability of the graft, with the most frequent complications being dislocation-detachment and, to a lesser extent, endothelial rejection. The studies that assess DSAEK are case series, and for the most part retrospective. The quality of this type of studies is both low and limited. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Imaging of pulmonary emphysema: A pictorial review

PubMed Central

Takahashi, Masashi; Fukuoka, Junya; Nitta, Norihisa; Takazakura, Ryutaro; Nagatani, Yukihiro; Murakami, Yoko; Otani, Hideji; Murata, Kiyoshi

2008-01-01

The term ‘emphysema’ is generally used in a morphological sense, and therefore imaging modalities have an important role in diagnosing this disease. In particular, high resolution computed tomography (HRCT) is a reliable tool for demonstrating the pathology of emphysema, even in subtle changes within secondary pulmonary lobules. Generally, pulmonary emphysema is classified into three types related to the lobular anatomy: centrilobular emphysema, panlobular emphysema, and paraseptal emphysema. In this pictorial review, we discuss the radiological – pathological correlation in each type of pulmonary emphysema. HRCT of early centrilobular emphysema shows an evenly distributed centrilobular tiny areas of low attenuation with ill-defined borders. With enlargement of the dilated airspace, the surrounding lung parenchyma is compressed, which enables observation of a clear border between the emphysematous area and the normal lung. Because the disease progresses from the centrilobular portion, normal lung parenchyma in the perilobular portion tends to be preserved, even in a case of far-advanced pulmonary emphysema. In panlobular emphysema, HRCT shows either panlobular low attenuation or ill-defined diffuse low attenuation of the lung. Paraseptal emphysema is characterized by subpleural well-defined cystic spaces. Recent topics related to imaging of pulmonary emphysema will also be discussed, including morphometry of the airway in cases of chronic obstructive pulmonary disease, combined pulmonary fibrosis and pulmonary emphysema, and bronchogenic carcinoma associated with bullous lung disease. PMID:18686729

Effects of marijuana smoking on the lung.

PubMed

Tashkin, Donald P

2013-06-01

Regular smoking of marijuana by itself causes visible and microscopic injury to the large airways that is consistently associated with an increased likelihood of symptoms of chronic bronchitis that subside after cessation of use. On the other hand, habitual use of marijuana alone does not appear to lead to significant abnormalities in lung function when assessed either cross-sectionally or longitudinally, except for possible increases in lung volumes and modest increases in airway resistance of unclear clinical significance. Therefore, no clear link to chronic obstructive pulmonary disease has been established. Although marijuana smoke contains a number of carcinogens and cocarcinogens, findings from a limited number of well-designed epidemiological studies do not suggest an increased risk for the development of either lung or upper airway cancer from light or moderate use, although evidence is mixed concerning possible carcinogenic risks of heavy, long-term use. Although regular marijuana smoking leads to bronchial epithelial ciliary loss and impairs the microbicidal function of alveolar macrophages, evidence is inconclusive regarding possible associated risks for lower respiratory tract infection. Several case reports have implicated marijuana smoking as an etiologic factor in pneumothorax/pneumomediastinum and bullous lung disease, although evidence of a possible causal link from epidemiologic studies is lacking. In summary, the accumulated weight of evidence implies far lower risks for pulmonary complications of even regular heavy use of marijuana compared with the grave pulmonary consequences of tobacco.

Cytokines in the sera of patients with pemphigus vulgaris: interleukin-6 and tumour necrosis factor-alpha levels are significantly increased as compared to healthy subjects and correlate with disease activity.

PubMed

D'Auria, L; Bonifati, C; Mussi, A; D'Agosto, G; De Simone, C; Giacalone, B; Ferraro, C; Ameglio, F

1997-12-01

Cytokine serum levels, when detectable, are currently measured in many disease states, both to evaluate a possible pathogenetic involvement of such molecules and for clinical purposes. No data are currently available on the cytokine levels in the sera of patients with pemphigus vulgaris (PV), a rare bullous disease of autoimmune origin. This study presents data concerning the levels of 13 different cytokines assayed in the sera of 25 patients affected with PV as compared with 20 healthy subjects using high sensitivity ELISA kits. Of the 13 molecules analyzed, no differences in the levels of most cytokines were observed between pemphigus and control sera, with the exception of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Serum TNF-alpha and IL-6 levels were found to be significantly higher in PV patients than in normal controls (p < 0.001). Furthermore, the levels of the two cytokines decreased after one month of corticosteroid therapy. A significant correlation was found between the serum levels of both TNF-alpha and IL-6 and the number of lesions for each patient (p < 0.001). The data presented support an involvement of at least IL-6 and TNF-alpha in the biological modifications associated with PV manifestations.

Immune response in pemphigus and beyond: progresses and emerging concepts.

PubMed

Di Zenzo, Giovanni; Amber, Kyle T; Sayar, Beyza S; Müller, Eliane J; Borradori, Luca

2016-01-01

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two severe autoimmune bullous diseases of the mucosae and/or skin associated with autoantibodies directed against desmoglein (Dsg) 3 and/or Dsg1. These two desmosomal cadherins, typifying stratified epithelia, are components of cell adhesion complexes called desmosomes and represent extra-desmosomal adhesion receptors. We herein review the advances in our understanding of the immune response underlying pemphigus, including human leucocyte antigen (HLA) class II-associated genetic susceptibility, characteristics of pathogenic anti-Dsg antibodies, antigenic mapping studies as well as findings about Dsg-specific B and T cells. The pathogenicity of anti-Dsg autoantibodies has been convincingly demonstrated. Disease activity and clinical phenotype correlate with anti-Dsg antibody titers and profile while passive transfer of anti-Dsg IgG from pemphigus patients' results in pemphigus-like lesions in neonatal and adult mice. Finally, adoptive transfer of splenocytes from Dsg3-knockout mice immunized with murine Dsg3 into immunodeficient mice phenotypically recapitulates PV. Although the exact pathogenic mechanisms leading to blister formation have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation, at least for PV. These new insights not only highlight the key role of Dsgs in maintenance of tissue homeostasis but are expected to progressively change pemphigus management, paving the way for novel targeted immunologic and pharmacologic therapies.

No-Touch Technique and a New Donor Adjuster for Descemet's Stripping Automated Endothelial Keratoplasty

PubMed Central

Kobayashi, Akira; Yokogawa, Hideaki; Sugiyama, Kazuhisa

2012-01-01

Purpose One difficulty with Descemet's stripping automated endothelial keratoplasty (DSAEK) is air management during surgery and donor endothelial lamella centering. We evaluated the no-touch technique for donor centering and the use of a newly developed DSAEK donor adjuster. Methods We evaluated the records of 12 consecutive patients (mean age 75.3 years) with bullous keratopathy who had undergone DSAEK. In all cases, the no-touch technique was attempted first. When the no-touch technique failed, a DSAEK donor adjuster with a 30-gauge cannula resembling a curved reverse Sinskey hook was used for donor centering. The adjuster allows air injection during donor centering. Results The no-touch technique using simple corneal surface massage to center the graft was successful in 4 cases (33.3%), while 4 cases required ocular tilting (33.3%) in addition to corneal surface massage. The no-touch technique was ineffective in 4 cases (33.3%), but the donor adjuster was used successfully and easily for these patients. Comparing the endothelial cell loss rate between the no-touch technique group and the donor adjuster group, there was no significant difference at 6 months. Conclusions The no-touch technique was useful for better control of DSAEK donor centering in most cases. When the no-touch technique was ineffective, the DSAEK donor adjuster was uniformly successful. PMID:22807910

Cocaine-induced pulmonary changes: HRCT findings *

PubMed Central

de Almeida, Renata Rocha; Zanetti, Gláucia; Souza, Arthur Soares; de Souza, Luciana Soares; Silva, Jorge Luiz Pereira e; Escuissato, Dante Luiz; Irion, Klaus Loureiro; Mançano, Alexandre Dias; Nobre, Luiz Felipe; Hochhegger, Bruno; Marchiori, Edson

2015-01-01

Abstract Objective: To evaluate HRCT scans of the chest in 22 patients with cocaine-induced pulmonary disease. Methods: We included patients between 19 and 52 years of age. The HRCT scans were evaluated by two radiologists independently, discordant results being resolved by consensus. The inclusion criterion was an HRCT scan showing abnormalities that were temporally related to cocaine use, with no other apparent causal factors. Results: In 8 patients (36.4%), the clinical and tomographic findings were consistent with "crack lung", those cases being studied separately. The major HRCT findings in that subgroup of patients included ground-glass opacities, in 100% of the cases; consolidations, in 50%; and the halo sign, in 25%. In 12.5% of the cases, smooth septal thickening, paraseptal emphysema, centrilobular nodules, and the tree-in-bud pattern were identified. Among the remaining 14 patients (63.6%), barotrauma was identified in 3 cases, presenting as pneumomediastinum, pneumothorax, and hemopneumothorax, respectively. Talcosis, characterized as perihilar conglomerate masses, architectural distortion, and emphysema, was diagnosed in 3 patients. Other patterns were found less frequently: organizing pneumonia and bullous emphysema, in 2 patients each; and pulmonary infarction, septic embolism, eosinophilic pneumonia, and cardiogenic pulmonary edema, in 1 patient each. Conclusions: Pulmonary changes induced by cocaine use are varied and nonspecific. The diagnostic suspicion of cocaine-induced pulmonary disease depends, in most of the cases, on a careful drawing of correlations between clinical and radiological findings. PMID:26398752

Black patients of African descent and HLA-DRB1*15:03 frequency overrepresented in epidermolysis bullosa acquisita.

PubMed

Zumelzu, Coralie; Le Roux-Villet, Christelle; Loiseau, Pascale; Busson, Marc; Heller, Michel; Aucouturier, Françoise; Pendaries, Valérie; Lièvre, Nicole; Pascal, Francis; Brette, Marie-Dominique; Doan, Serge; Charron, Dominique; Caux, Fréderic; Laroche, Liliane; Petit, Antoine; Prost-Squarcioni, Catherine

2011-12-01

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune bullous disease (AIBD). However, higher EBA incidence and predisposing genetic factor(s) involving an HLA haplotype have been suspected in some populations. This retrospective study assessed the overrepresentation of black patients with EBA, its link with HLA-DRB1*15:03, and their clinical and immunological characteristics. Between 2005 and 2009, 7/13 (54%) EBA and 6/183 (3%) other-AIBD patients seen consecutively in our department were black (P=10(-6)); moreover 7/13 (54%) black patients and 6/183 (3%) white patients had EBA (P=10(-6)). In addition, between 1983 and 2005, 12 black patients had EBA. Finally, among the 19 black EBA patients, most of them had very atypical clinical presentations, 9 were natives of sub-Saharan Africa, 1 from Reunion Island, 7 from the West Indies, and 2 were of mixed ancestry. HLA-DRB1*15:03 allelic frequencies were 50% for African patients, significantly higher than the control population (P<10(-3)), and 21% for the West Indians (nonsignificant). High EBA frequencies have already been reported in American blacks significantly associated with the HLA-DR2. In conclusion, black-skinned patients developing EBA seem to have a genetic predisposition, and EBA should be suspected systematically for every AIBD seen in this population.

Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus.

PubMed

Bifulco, Giuseppe; Mandato, Vincenzo D; Piccoli, Roberto; Giampaolino, Pierluigi; Mignogna, Chiara; Mignogna, Michele D; Costagliola, Luigi; Nappi, Carmine

2010-06-23

Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes. Genital involvement occurs when most other common sites are concurrently affected or are in remission. Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many parts of the body and the skin with occasional bullous lesions. Pemphigus vulgaris and SLE may be associated, albeit rarely. Here, we report the first case of a woman affected with SLE presenting with early invasive squamous cell carcinoma (SCC) arising from Pemphigus Vulgaris of the vulva. A 27-year-old Caucasian woman was admitted to our Gynaecology Unit for bleeding vegetant lesions of the vulva. Her history was characterized by systemic lupus erythematosus and PV. Biopsy showed concomitant PV and vulvar intraepithelial neoplasia (VIN) grade 3. One month later a new biopsy revealed progression from VIN 3 to early SCC. Despite chemotherapy, no remission of disease was observed. She died six months after diagnosis Our case underlines PV as another chronic inflammatory disease of the lower genital tract predisposing to VIN-SCC. It suggests the need for careful follow-up of patients with chronic inflammatory disease, especially when concomitant autoimmune disorders are present. Moreover, a biopsy should be always performed if there are PV lesions because of the possibility of neoplastic disease.

Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus

PubMed Central

2010-01-01

Background Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes. Genital involvement occurs when most other common sites are concurrently affected or are in remission. Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many parts of the body and the skin with occasional bullous lesions. Pemphigus vulgaris and SLE may be associated, albeit rarely. Here, we report the first case of a woman affected with SLE presenting with early invasive squamous cell carcinoma (SCC) arising from Pemphigus Vulgaris of the vulva. Case presentation A 27-year-old Caucasian woman was admitted to our Gynaecology Unit for bleeding vegetant lesions of the vulva. Her history was characterized by systemic lupus erythematosus and PV. Biopsy showed concomitant PV and vulvar intraepithelial neoplasia (VIN) grade 3. One month later a new biopsy revealed progression from VIN 3 to early SCC. Despite chemotherapy, no remission of disease was observed. She died six months after diagnosis Conclusion Our case underlines PV as another chronic inflammatory disease of the lower genital tract predisposing to VIN-SCC. It suggests the need for careful follow-up of patients with chronic inflammatory disease, especially when concomitant autoimmune disorders are present. Moreover, a biopsy should be always performed if there are PV lesions because of the possibility of neoplastic disease. PMID:20573220

"All-laser" endothelial corneal transplant in human patients

NASA Astrophysics Data System (ADS)

Rossi, Francesca; Menabuoni, Luca; Malandrini, Alex; Canovetti, Annalisa; Lenzetti, Ivo; Pini, Roberto

2012-03-01

Femtosecond laser sculpturing of corneal tissue is commonly used for the preparation of endothelial flaps. Diode laser welding of ocular tissues is a procedure that enables minimally invasive suturing of tissues. The combination of these laser based techniques results in a new approach to minimally invasive ophthalmic surgery, such as in endothelial corneal transplant (or endothelial keratoplasty - EK). In this work we present the "all laser" EK performed in human subjects. 24 pseudophakic patients with bullous keratopathy underwent EK: the femtosecond laser was used to prepare the 100 ìm thick and 8.5 mm diameter donor Descemet endothelial flap. After staining the stromal layer of the donor flap with a liquid ICG solution, the donor flap was inserted in the recipient eye by the use of the Busin injector. Then, the endothelial layer was laser-welded to the recipient eye (10 laser spots around the periphery of the flap), in order to reduce the risk of postoperative dislocation of the transplanted flap. A transplanted flap engraftment was observed in all the treated eyes. The staining procedure used to perform laser welding also enabled to evidence the stromal side of the donor flap, so as the flap was always placed in the right side position. The endothelial cells counts in both the laserwelded flaps and in a control group were in good agreement. The proposed technique is easy to perform and enables the reduction of postoperative endothelial flap dislocations.

Antigastric parietal cell and antithyroid autoantibodies in patients with desquamative gingivitis.

PubMed

Chang, Julia Yu-Fong; Chiang, Chun-Pin; Wang, Yi-Ping; Wu, Yang-Che; Chen, Hsin-Ming; Sun, Andy

2017-04-01

Desquamative gingivitis (DG) is principally associated with erosive oral lichen planus (EOLP), mucous membrane pemphigoid (MMP), and pemphigus vulgaris (PV). Serum autoantibodies including antigastric parietal cell antibody (GPCA), antithyroglobulin antibody (TGA), and antithyroid microsomal antibody (TMA) were measured in 500 patients with DG, 287 EOLP without DG (EOLP/DG - ) patients, and 100 healthy control subjects. The 500 patients with DG were diagnosed as having EOLP in 455 (91%), PV in 40 (8%), and MMP in five (1%) patients. We found that 37.0%, 43.6%, and 42.6% of 500 patients with DG, 39.6%, 46.4%, and 45.1% of 455 EOLP with DG (EOLP/DG) patients, and 18.5%, 27.5%, and 30.3% of 287 EOLP/DG - patients had the presence of GPCA, TGA, and TMA in their sera, respectively. DG, EOLP/DG, and EOLP/DG - patients all had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control subjects (all P-values < 0.001). Moreover, 455 EOLP/DG patients had a significantly higher frequency of GPCA, TGA, or TMA positivity than 287 EOLP/DG - patients (all P-values < 0.001). Of 210 TGA/TMA-positive patients with DG whose serum thyroid-stimulating hormone (TSH) levels were measured, 84.3%, 6.7%, and 9.0% patients had normal, lower, and higher serum TSH levels, respectively. We conclude that 73.4% DG, 77.1% EOLP/DG, and 47.4% EOLP/DG - patients may have GPCA/TGA/TMA positivity in their sera. Because part of GPCA-positive patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and part of TGA/TMA-positive patients may have thyroid dysfunction, these patients should be referred to medical department for further management. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of clinical factors on the long-term functional and anatomic outcomes of osteo-odonto-keratoprosthesis and tibial bone keratoprosthesis.

PubMed

De La Paz, María Fideliz; De Toledo, Juan Álvarez; Charoenrook, Victor; Sel, Saadettin; Temprano, José; Barraquer, Rafael I; Michael, Ralph

2011-05-01

To report the long-term functional and anatomic outcomes of osteo-odonto-keratoprosthesis and tibial bone keratoprosthesis; to analyze the influence of clinical factors, such as surgical technique, primary diagnosis, age, and postoperative complications, on the final outcome. Retrospective cohort study. setting: Centro de Oftalmología Barraquer, between 1974 and 2005. Two hundred twenty-seven patients. intervention: Biological keratoprosthesis using osteo-odonto-keratoprosthesis or tibial bone keratoprosthesis. main outcome measures: Functional survival with success defined as best-corrected visual acuity ≥0.05; anatomic survival with success defined as retention of the keratoprosthesis lamina. Osteo-odonto-keratoprosthesis and tibial bone keratoprosthesis have comparable anatomic survival at 5 and 10 years of follow-up, but osteo-odonto-keratoprosthesis has a significantly better functional success than tibial bone keratoprosthesis at the same time periods. Among the primary diagnoses, Stevens-Johnson syndrome, chemical burn, and trachoma have generally good functional and anatomic outcomes and the least favorable prognosis is for ocular cicatricial pemphigoid. Younger patients fared better than those in older age groups. The most frequent complications were extrusion (28%), retinal detachment (16%), and uncontrolled glaucoma (11%). The glaucoma group had the best anatomic success but the worst functional results, only exceeded by the retinal detachment group in terms of functional outcome. Clinical factors, such as surgical technique, primary diagnosis, age, and postoperative complications, can affect the long-term anatomic and functional successes of biological keratoprosthesis. Knowledge about the impact of each of these factors on survival can help surgeons determine the best approach in every particular case. Copyright © 2011 Elsevier Inc. All rights reserved.

Development of a conjunctival tissue substitute on the basis of plastic compressed collagen.

PubMed

Drechsler, C C; Kunze, A; Kureshi, A; Grobe, G; Reichl, S; Geerling, G; Daniels, J T; Schrader, S

2017-03-01

Ocular surface disorders, such as pterygium, cicatricial pemphigoid and external disruptions, can cause severe inflammation, scarring, fornix shortening as well as ankyloblepharon. Current treatments do not resolve these conditions sufficiently. The aim of this study was to evaluate clinical applicability and suitability of plastic compressed collagen to serve as a substrate for the expansion of human conjunctival epithelial cells in order to develop an epithelialized conjunctival substitute for fornix reconstruction. Human conjunctival epithelial cells were expanded on plastic compressed collagen gels. Epithelial cell characteristics were evaluated by haematoxylin and eosin staining, electron microscopy and cytokeratin expression. The expression of putative epithelial progenitor cell markers p63α, ABCG2 and CK15 was assessed by immunostaining. The proliferative capacity and clonal growth of the cells was evaluated before (P0) and after expansion (P1) on the plastic compressed collagen gels by colony forming efficiency assay. The potential clinical applicability of this gel substitutes was evaluated by assessment of their biomechanical properties as well as their surgical handling. Human conjunctival epithelial cells cultured on plastic and plastic compressed collagen gels formed a confluent cell layer and expressed CK19. The cells showed expression of the putative epithelial progenitor cell markers p63α, ABCG2 and CK15 and sustained colony forming ability. The compressed collagen gels showed a high ultimate tensile strength and elasticity and the surgical handling of gels was comparable to amniotic membrane. An epithelialized conjunctival tissue construct on the basis of compressed collagen might therefore be a promising alternative bioartificial tissue substitute for conjunctival reconstruction. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Expression of prostaglandin E receptor subtype EP4 in conjunctival epithelium of patients with ocular surface disorders: case-control study.

PubMed

Ueta, Mayumi; Sotozono, Chie; Yamada, Keiko; Yokoi, Norihiko; Inatomi, Tsutomu; Kinoshita, Shigeru

2012-01-01

To confirm the downregulation of PTGER4 mRNA in the conjunctiva of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and ocular cicatricial pemphigoid (OCP) patients and to examine the expression of its EP4 protein in the conjunctival epithelium of patients with various ocular surface disorders. Case-control study. We performed quantitative reverse transcription-PCR (RT-PCR) analysis of PTGER4 mRNA in conjunctival tissue sections from patients with SJS/TEN and OCP to confirm the downregulation of PTGER4 mRNA expression. We also analysed EP4 immunohistologically in other ocular surface disorders. Conjunctival tissues were obtained from patients undergoing surgical reconstruction of the ocular surface due to chemical eye burns, subacute SJS/TEN or chronic SJS/TEN, chronic OCP, severe graft versus host disease (GVHD) and from patients with Mooren's ulcers treated by resection of the inflammatory conjunctiva. The expression of PTGER4 mRNA and EP4 protein assessed by quantitative RT-PCR assay and immunohistological methods. PTGER4 mRNA was significantly lower in conjunctival tissues from SJS and OCP patients than in the control conjunctivochalasis samples. EP4 protein was detected in conjunctival epithelium from patients with chemical eye burn and in control conjunctival epithelium from patients with conjunctivochalasis. Its expression varied in conjunctival epithelium from patients with Mooren's ulcer. We did not detect EP4 immunoreactivity in conjunctival epithelium from patients with subacute SJS/TEN, severe GVHD, chronic SJS/TEN or OCP. The strong downregulation of EP4 expression in conjunctival epithelium from patients with OCP or SJS/TEN may be attributable to ocular surface inflammation.

Expression of prostaglandin E receptor subtype EP4 in conjunctival epithelium of patients with ocular surface disorders: case-control study

PubMed Central

Ueta, Mayumi; Sotozono, Chie; Yamada, Keiko; Yokoi, Norihiko; Inatomi, Tsutomu; Kinoshita, Shigeru

2012-01-01

Objectives To confirm the downregulation of PTGER4 mRNA in the conjunctiva of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and ocular cicatricial pemphigoid (OCP) patients and to examine the expression of its EP4 protein in the conjunctival epithelium of patients with various ocular surface disorders. Design Case-control study. Setting and participants We performed quantitative reverse transcription-PCR (RT-PCR) analysis of PTGER4 mRNA in conjunctival tissue sections from patients with SJS/TEN and OCP to confirm the downregulation of PTGER4 mRNA expression. We also analysed EP4 immunohistologically in other ocular surface disorders. Conjunctival tissues were obtained from patients undergoing surgical reconstruction of the ocular surface due to chemical eye burns, subacute SJS/TEN or chronic SJS/TEN, chronic OCP, severe graft versus host disease (GVHD) and from patients with Mooren's ulcers treated by resection of the inflammatory conjunctiva. Primary and secondary outcome measures The expression of PTGER4 mRNA and EP4 protein assessed by quantitative RT-PCR assay and immunohistological methods. Results PTGER4 mRNA was significantly lower in conjunctival tissues from SJS and OCP patients than in the control conjunctivochalasis samples. EP4 protein was detected in conjunctival epithelium from patients with chemical eye burn and in control conjunctival epithelium from patients with conjunctivochalasis. Its expression varied in conjunctival epithelium from patients with Mooren's ulcer. We did not detect EP4 immunoreactivity in conjunctival epithelium from patients with subacute SJS/TEN, severe GVHD, chronic SJS/TEN or OCP. Conclusions The strong downregulation of EP4 expression in conjunctival epithelium from patients with OCP or SJS/TEN may be attributable to ocular surface inflammation. PMID:23065448

Calcitriol Treatment Ameliorates Inflammation and Blistering in Mouse Models of Epidermolysis Bullosa Acquisita.

PubMed

Tukaj, Stefan; Bieber, Katja; Witte, Mareike; Ghorbanalipoor, Saeedeh; Schmidt, Enno; Zillikens, Detlef; Ludwig, Ralf J; Kasperkiewicz, Michael

2018-02-01

A link between hypovitaminosis D and development of autoimmune bullous disorders has been suggested recently, but this association has not been elaborated experimentally. Here, the role of vitamin D was investigated in epidermolysis bullosa acquisita (EBA), an anti-type VII collagen autoantibody-induced blistering skin disease. Oral administration of the hormonally active vitamin D metabolite calcitriol ameliorated clinical disease severity and dermal neutrophil infiltration in both an antibody transfer- and immunization-induced EBA mouse model. Mechanistically, calcitriol hindered immune effector cell activation as evidenced by increased L-selectin expression on Gr-1 + cells in calcitriol-treated mice with antibody transfer-induced EBA, as well as suppressed in vitro immune complex-induced reactive oxygen species production in calcitriol-treated murine neutrophils. Additionally, calcitriol administration was associated with an increase of regulatory T (CD4 + FoxP3 + ) and B (CD19 + IL10 + ) cells as well as reduction of pro-inflammatory T helper 17 (CD4 + IL-17 + ) cells in mice with immunization-induced EBA. In line, levels of circulating anti-type VII collagen autoantibodies were lower in mice that received calcitriol compared to solvent-treated animals. Together with the observed state of hypovitaminosis D in most cases of an analyzed EBA patient cohort, the results of this study support the use of vitamin D derivatives or analogs for patients with EBA and related diseases. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Surgical Outcomes of Additional Ahmed Glaucoma Valve Implantation in Refractory Glaucoma.

PubMed

Ko, Sung Ju; Hwang, Young Hoon; Ahn, Sang Il; Kim, Hwang Ki

2016-06-01

To evaluate the surgical outcomes of the implantation of an additional Ahmed glaucoma valve (AGV) into the eyes of patients with refractory glaucoma following previous AGV implantation. This study is a retrospective review of the clinical histories of 23 patients who had undergone a second AGV implantation after a failed initial implantation. Age, sex, prior surgery, glaucoma type, number of medications, intraocular pressure (IOP), visual acuity, and surgical complications were analyzed. Surgical success was defined as IOP maintained below 21 mm Hg, with at least a 20% overall reduction in IOP, regardless of the use of IOP-lowering medications. Following the implantation of a second AGV, the mean IOP decreased from 39.3 to 18.5 mm Hg (52.9% reduction, P<0.001). The mean number of postoperative IOP-lowering medications administered decreased from 2.8 to 1.7 after the second AGV implantation (P<0.001). The cumulative probability of success for the procedure was 87% after 1 year and 52% after 3 years. Three patients (13.0%) experienced bullous keratopathy after the second AGV implantation. None of the patients showed any evidence of diplopia or ocular movement limitation as a result of the presence of 2 AGVs in the same eye. Prior trabeculectomy was found to be a significant risk factor for failure (P=0.027). A second AGV implantation can be a good choice of surgical treatment when the first AGV has failed to control IOP.

Medical qualification of a commercial spaceflight participant: not your average astronaut.

PubMed

Jennings, Richard T; Murphy, David M F; Ware, David L; Aunon, Serena M; Moon, Richard E; Bogomolov, Valery V; Morgun, Valeri V; Voronkov, Yuri I; Fife, Caroline E; Boyars, Michael C; Ernst, Randy D

2006-05-01

Candidates for commercial spaceflight may be older than the typical astronaut and more likely to have medical problems that place them at risk during flight. Since the effects of microgravity on many medical conditions are unknown, physicians have little guidance when evaluating and certifying commercial spaceflight participants. This dynamic new era in space exploration may provide important data for evaluating medical conditions, creating appropriate medical standards, and optimizing treatment alternatives for long-duration spaceflight. A 57-yr-old spaceflight participant for an ISS mission presented with medical conditions that included moderately severe bullous emphysema, previous spontaneous pneumothorax with talc pleurodesis, a lung parenchymal mass, and ventricular and atrial ectopy. The medical evaluation required for certification was extensive and included medical studies and monitoring conducted in analogue spaceflight environments including altitude chambers, high altitude mixed-gas simulation, zero-G aircraft, and high-G centrifuge. To prevent recurrence of pneumothorax, we performed video-assisted thoracoscopic pleurodesis, and to assess lung masses, several percutaneous or direct biopsies. The candidate's 10-d mission was without incident. Non-career astronauts applying for commercial suborbital and orbital spaceflight will, at least in the near future, challenge aerospace physicians with unknowns regarding safety during training and flight, and highlight important ethical and risk-assessment problems. The information obtained from this new group of space travelers will provide important data for the evaluation and in-flight treatment of medical problems that space programs have not yet addressed systematically, and may improve the medical preparedness of exploration-class missions.

Recessive mutation in tetraspanin CD151 causes Kindler syndrome-like epidermolysis bullosa with multi-systemic manifestations including nephropathy.

PubMed

Vahidnezhad, Hassan; Youssefian, Leila; Saeidian, Amir Hossein; Mahmoudi, Hamidreza; Touati, Andrew; Abiri, Maryam; Kajbafzadeh, Abdol-Mohammad; Aristodemou, Sophia; Liu, Lu; McGrath, John A; Ertel, Adam; Londin, Eric; Kariminejad, Ariana; Zeinali, Sirous; Fortina, Paolo; Uitto, Jouni

2018-03-01

Epidermolysis bullosa (EB) is caused by mutations in as many as 19 distinct genes. We have developed a next-generation sequencing (NGS) panel targeting genes known to be mutated in skin fragility disorders, including tetraspanin CD151 expressed in keratinocytes at the dermal-epidermal junction. The NGS panel was applied to a cohort of 92 consanguineous families of unknown subtype of EB. In one family, a homozygous donor splice site mutation in CD151 (NM_139029; c.351+2T>C) at the exon 5/intron 5 border was identified, and RT-PCR and whole transcriptome analysis by RNA-seq confirmed deletion of the entire exon 5 encoding 25 amino acids. Immunofluorescence of proband's skin and Western blot of skin proteins with a monoclonal antibody revealed complete absence of CD151. Transmission electron microscopy showed intracellular disruption and cell-cell dysadhesion of keratinocytes in the lower epidermis. Clinical examination of the 33-year old proband, initially diagnosed as Kindler syndrome, revealed widespread blistering, particularly on pretibial areas, poikiloderma, nail dystrophy, loss of teeth, early onset alopecia, and esophageal webbing and strictures. The patient also had history of nephropathy with proteinuria. Collectively, the results suggest that biallelic loss-of-function mutations in CD151 underlie an autosomal recessive mechano-bullous disease with systemic features. Thus, CD151 should be considered as the 20th causative, EB-associated gene. Copyright © 2017 Elsevier B.V. All rights reserved.

Specific skin signs as a cutaneous marker of diabetes mellitus and the prediabetic state - a systematic review.

PubMed

Bustan, Rewend Salman; Wasim, Daanyaal; Yderstræde, Knud Bonnet; Bygum, Anette

2017-01-01

Diabetes mellitus and the prediabetic state are associated with a number of skin manifestations. This study is a systematic review of the following manifestations: acanthosis nigricans (AN), skin tags (ST), diabetic dermopathy (DD), rubeosis faciei (RF), pruritus (PR), granuloma annulare (GA), necrobiosis lipoidica (NL), scleroedema diabeticorum (SD) and bullosis diabeticorum (BD). These conditions possibly relate to underlying diabetogenic mechanisms. Our aim was to determine whether skin signs are feasible as cutaneous markers for the prediabetic or diabetic state. Data were collected from the databases PubMed, Embase and Cochrane. Articles were excluded if the populations presented with comorbidities or received treatment with drugs affecting the skin. Also, animal studies, studies with poor methodology and pilot studies were excluded. Among the 34 included original articles, an association with diabetes was shown as follows: in eight articles with AN, five articles with ST, three articles with GA, two articles with NL, PR and SD respectively and in one article with RF. Three papers indirectly showed an association of DD with diabetes. Association between bullous skin lesions and diabetes was only documented by case reports and case series. The results indicate a benefit of diabetes screening in individuals presenting with AN, ST or BD. Further studies are required to enlighten a possible association with RF, GA, SD or NL. Until such studies are available, it is advisable to screen individuals with the skin lesions presented by measuring their glycated haemoglobin.

Graft failure: III. Glaucoma escalation after penetrating keratoplasty.

PubMed

Greenlee, Emily C; Kwon, Young H

2008-06-01

Glaucoma after penetrating keratoplasty is a frequently observed post-operative complication and is a risk factor for graft failure. Penetrating keratoplasty performed for aphakic and pseudophakic bullous keratopathy and inflammatory conditions are more likely to cause postoperative glaucoma compared with keratoconus and Fuchs' endothelial dystrophy. The intraocular pressure elevation may occur immediately after surgery or in the early to late postoperative period. Early postoperative causes of glaucoma include pre-existing glaucoma, retained viscoelastic, hyphema, inflammation, pupillary block, aqueous misdirection, or suprachoroidal hemorrhage. Late causes include pre-existing glaucoma, angle-closure glaucoma, ghost cell glaucoma, suprachoroidal hemorrhage, and steroid-induced glaucoma. Determining the cause of IOP elevation can help guide therapeutic intervention. Treatments for refractory glaucoma include topical anti-glaucoma medications such as beta-adrenergic blockers. Topical carbonic anhydrase inhibitors, miotic agents, adrenergic agonists, and prostaglandin analogs should be used with caution in the post-keratoplasty patient, because of the possibility of corneal decompensation, cystoid macular edema, or persistent inflammation. Various glaucoma surgical treatments have reported success in post-keratoplasty glaucoma. Trabeculectomy with mitomycin C can be successful in controlling IOP without the corneal toxicity noted with 5-fluorouracil. Glaucoma drainage devices have successfully controlled intraocular pressure in postkeratoplasty glaucoma; this is, however, associated with increased risk of graft failure. Placement of the tube through the pars plana may improve graft success compared with implantation within the anterior chamber. In addition, cyclophotocoagulation remains a useful procedure for eyes that have refractory glaucoma despite multiple surgical interventions.

Evaluation of cases of pemphigus vulgaris and pemphigus foliaceus from a reference service in Pará state, Brazil.

PubMed

Pires, Carla Andréa Avelar; Viana, Viviane Brito; Araújo, Fernando Costa; Müller, Silvia Ferreira Rodrigues; Oliveira, Miguel Saraty de; Carneiro, Francisca Regina Oliveira

2014-01-01

Pemphigusis a bullous, rare and chronic autoimmune disease. There are two major forms of pemphigus: vulgaris and foliaceus. Epidemiological data and clinical outcome in patients diagnosed in the Brazilian Amazon states are still rare. To study the occurrence of the disease during the study period and analyze the epidemiological profile of patients, the most common subtype of pemphigus, and the clinical evolution of patients. Retrospective analysis of medical records of hospitalized patients with pemphigus foliaceus and pemphigus vulgaris in the period from 2003 to 2010 in Dermatology Service of Hospital Fundação Santa Casa de Misericórdia do Pará, Belém, Northern Brazil. We found a total of 20 cases of pemphigus during the study period, 8 of which were of foliaceus pemphigus and 12 of vulgaris pemphigus. Pemphigus foliaceus had the predominance of male patients (75%), showed satisfactory clinical evolution, and was characterized by absence of pediatric cases. Pemphigus vulgaris affected more women (66.7%), showed mean hospital stay of 1 to 3 months (50%), and there were three cases of death (25%). The prescribed immunosuppressive drugs included prednisone with or without combination of azathioprine and/or dapsone. Sepsis was associated with 100% of the deaths. The occurrence of the disease is rare, there are no familiar/endemic outbreaks in the sample. Evolution is usually favorable, but secondary infection is associated with worse prognosis. The choice of best drugs to treat pemphigus remains controversial.

GM-CSF modulates autoantibody production and skin blistering in experimental epidermolysis bullosa acquisita.

PubMed

Samavedam, Unni Krishna S R L; Iwata, Hiroaki; Müller, Susen; Schulze, Franziska S; Recke, Andreas; Schmidt, Enno; Zillikens, Detlef; Ludwig, Ralf J

2014-01-15

GM-CSF activates hematopoietic cells and recruits neutrophils and macrophages to sites of inflammation. Inhibition of GM-CSF attenuates disease activity in models of chronic inflammatory disease. Effects of GM-CSF blockade were linked to modulation of the effector phase, whereas effects on early pathogenic events, for example, Ab production, have not been identified. To evaluate yet uncharacterized effects of GM-CSF on early pathogenic events in chronic inflammation, we employed immunization-induced epidermolysis bullosa acquisita (EBA), an autoimmune bullous disease caused by autoantibodies to type VII collagen. Compared to wild-type mice, upon immunization, GM-CSF(-/-) mice produced lower serum autoantibody titers, which were associated with reduced neutrophil numbers in draining lymph nodes. The same effect was observed in neutrophil-depleted wild-type mice. Neutrophil depletion in GM-CSF(-/-) mice led to a stronger inhibition, indicating that GM-CSF and neutrophils have additive functions. To characterize the contribution of GM-CSF specifically in the effector phase of EBA, disease was induced by transfer of anti-type VII collagen IgG into mice. We observed an increased GM-CSF expression, and GM-CSF blockade reduced skin blistering. Additionally, GM-CSF enhanced reactive oxygen species release and neutrophil migration in vitro. In immunization-induced murine EBA, treatment with anti-GM-CSF had a beneficial effect on established disease. We demonstrate that GM-CSF modulates both autoantibody production and skin blistering in a prototypical organ-specific autoimmune disease.

Ultra-wide-field autofluorescence imaging in non-traumatic rhegmatogenous retinal detachment

PubMed Central

Witmer, M T; Cho, M; Favarone, G; Paul Chan, R V; D'Amico, D J; Kiss, S

2012-01-01

Purpose Rhegmatogenous retinal detachment (RRD) affects the function of the retina before and after surgical repair. We investigated ultra-wide-field autofluorescence (UAF) abnormalities in patients with acute RRD to improve our understanding of the functional changes in the retina before and after surgery. Methods In this retrospective study, we present the UAF imaging findings of 16 patients with acute, non-traumatic RRD. Imaging was obtained with the Optos 200 Tx (Optos) in 14 eyes preoperatively and in 12 eyes postoperatively. Twelve eyes had RRDs that involved the macula (group A), whereas four eyes had macula-sparing RRDs (group B). Results All patients (100%) with bullous retinal detachments demonstrated hypofluorescence over the area of retinal detachment. A hyperfluorescent leading edge (HLE) to the retinal detachment was observed preoperatively in 100% of eyes in group A and 75% of eyes in group B. Preoperative UAF through the fovea of group A eyes was normal (30%), hypofluorescent (50%) or hyperfluorescent (20%). In all patients with a HLE preoperatively, the HLE resolved by the 1-month postoperative visit. A residual line of demarcation remained in 8 of the 12 eyes (67%). In group A eyes, postoperative granular autofluorescent changes were present in four of the nine (44%) eyes, and were associated with worse preoperative (P=0.04) and postoperative (P=0.09) visual acuity. Conclusion UAF imaging reveals abnormalities in RRDs that allow excellent demarcation of the extent of the retinal detachment and assist in preoperative characterization of the detachment and postoperative counselling. PMID:22722489

Clinical application of multiphoton tomography in combination with high-frequency ultrasound for evaluation of skin diseases.

PubMed

König, Karsten; Speicher, Marco; Köhler, Martin J; Scharenberg, Rüdiger; Kaatz, Martin

2010-12-01

The first-ever application of high-frequency ultrasound combined with multiphoton tomography (MPT) and dermoscopy in a clinical trial is reported. 47 patients with different dermatoses such as benign and malign skin cancers, connective tissue diseases, inflammatory skin diseases, and autoimmune bullous skin diseases have been investigated with (i) state-of-the-art and highly sophisticated ultrasound systems for dermatology, (ii) the femtosecond laser multiphoton tomograph and (iii) dermoscopes. Dermoscopy provides two-dimensional color images of the skin surface with a magnification up to 70 x. Depending on the ultrasonic frequencies from 7.5 MHz to 100 MHz, the signal depth varies from about 1 mm to 80 mm. Vertical ultrasound wide-field images provide fast information on depth and volume of the lesion. The 100 MHz ultrasound allows imaging with resolutions down to 16 μm (axial) and 32 μm (lateral). Multiphoton tomography provides 0.36 x 0.36 x 0.001 mm³ horizontal optical sections of a particular region of interest with submicron resolution down to 200 μm tissue depth. The autofluorescence of mitochondrial coenzymes, keratin, melanin, and elastin as well as the network of collagen structures can be imaged. The combination of ultrasound and MPT opens novel synergistic possibilities in diagnostics of skin diseases with a special focus on the early detection of skin cancer as well as the evaluation of treatments. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Indications and outcomes of pediatric keratoplasty in a tertiary eye care center: A retrospective review.

PubMed

Gulias-Cañizo, Rosario; Gonzalez-Salinas, Roberto; Hernandez-Zimbron, Luis Fernando; Hernandez-Quintela, Everardo; Sanchez-Huerta, Valeria

2017-11-01

To evaluate indications and outcomes of pediatric keratoplasty in a tertiary eye center, and identify factors that affect visual outcomes.We performed a retrospective review of penetrating keratoplasty in children aged 0 to 18 years between 1995 and 2011 in the Asociación para Evitar la Ceguera en México IAP, Hospital "Dr. Luis Sánchez Bulnes".A total of 574 penetrating keratoplasties were performed during the study interval. Median follow-up was 5.0 years. Main indications included keratoconus (55.58%), postherpetic scarring (9.58%), traumatic opacities (7.49%), and bullous keratopathy (6.09%). Rejection rates at 5 years were 27% overall, and among indications, keratoconus showed the best graft survival at 60-months follow-up (85%). The percentage of patients with best corrected visual acuity (BCVA) posttransplant >20/400 at 5 years in the nonrejection group was 81.25% and 82.74% in < and > 10 years of age (YOA) groups, respectively, versus a BCVA posttransplant > 20/400 at 5 years in the rejection group of 53.68% and 51.72% in < and > 10 YOA groups, respectively. There was a statistically significant reduced rejection rate between genders at 18 months of follow-up, favoring males.Despite being considered a high-risk procedure in children, penetrating keratoplasty can achieve good results, especially in patients with keratoconus. It can achieve significative improvements of visual acuity, provided there is an adequate follow-up and treatment adherence.

Autoantibodies other than Anti-desmogleins in Pemphigus Vulgaris Patients

PubMed Central

Saleh, Marwah Adly; Salem, Hedayat; El Azizy, Hoda

2017-01-01

Background: Pemphigus vulgaris (PV) is an immunoglobulin G-mediated autoimmune bullous skin disease. Nonorgan-specific antibodies were detected in Tunisian and Brazilian pemphigus patients with different prevalence. Materials and Methods: Fifty PV patients and fifty controls were screened for antinuclear antibodies (ANAs), anti-smooth muscle antibodies (ASMAs), anti-parietal antibodies (APAs), anti-mitochondrial antibodies, and Anti-nuclear cytoplasmic antibodies (ANCA) by indirect immunofluorescence. Results: Thirty-nine patients were female and 11 were male. Fifteen patients did not receive treatment before while 35 patients were on systemic steroid treatment ± azathioprine. Twenty (40%) of the PV patients and 1 (2%) control had positive ANA. ANA was significantly higher in PV patients than controls, P < 0.0001. ASMAs were detected in 20 (40%) PV patients and none of the controls. ASMA was significantly higher in PV patients than controls, P < 0.0001. No significant difference was detected between treated and untreated regarding ANA, P - 0.11. However, there was a significant difference between treated and untreated regarding ASMA, P - 0.03. Six patients (12%) and none of the controls had positive APA. There was a significant difference between the patients and the controls in APA. P - 0.027. Conclusion: Egyptian PV patients showed more prevalent ANA, ASMA, and APA than normal controls. Follow-up of those patients is essential to detect the early development of concomitant autoimmune disease. Environmental factors might account for the variability of the nonorgan-specific antibodies among different populations. PMID:28216725

Lenalidomide for refractory cutaneous manifestations of pediatric systemic lupus erythematosus.

PubMed

Wu, E Y; Schanberg, L E; Wershba, E C; Rabinovich, C E

2017-05-01

Objective Cutaneous manifestations of pediatric systemic lupus erythematosus cause significant morbidity. Lenalidomide, a thalidomide analogue, has shown promise treating cutaneous lupus erythematosus in adults. Our objective was to evaluate lenalidomide's efficacy and safety in treating refractory cutaneous manifestations of pediatric systemic lupus erythematosus. Methods We performed a retrospective chart review of 10 adolescents who received lenalidomide for recalcitrant cutaneous lupus erythematosus. Information was gathered at drug initiation and 6-month follow-up. The Wilcoxon matched-pairs signed-rank test was used to assess change in quantitative parameters of disease activity. Results Nine subjects were girls and six were African-American. Indications for lenalidomide treatment included alopecia, nasal and oral ulcers, extensive malar rash, discoid lesions, bullous lesions, panniculitis, cutaneous vasculitis, and Raynaud's phenomenon with digital ulcerations. Within 6 months, all patients demonstrated complete or near resolution based on physician report. Prednisone dose decreased from a mean 23.5 mg (SD± 13.3) to 12.25 mg (SD± 9.2) ( P= 0.008). Sedimentation rate decreased from a mean 29 mm/hour (SD± 31.5) to 17 mm/hour (SD± 18.1) ( P= 0.004). Lenalidomide was well tolerated. Conclusion Lenalidomide is an effective and safe treatment for a spectrum of dermatological conditions in pediatric systemic lupus erythematosus. Its use may allow a reduction in prednisone dose and decreased disfigurement. Prospective study is needed to clarify lenalidomide's role in treating cutaneous manifestations of systemic lupus erythematosus.

Clinical features and histological description of tongue lesions in a large Northern Italian population

PubMed Central

Carbone, Mario; Arduino, Paolo-Giacomo; Carrozzo, Marco; Conrotto, Davide; Tanteri, Carlotta; Carbone, Lucio; Elia, Alessandra; Maragon, Zaira; Broccoletti, Roberto

2015-01-01

Background Only few studies on tongue lesions considered sizable populations, and contemporary literature does not provide a valid report regarding the epidemiology of tongue lesions within the Italian population. In this report, the histopathological and clinical appearance of 1.106 tongue lesions from northern Italians are described and discussed. Material and Methods The case records of patients referred for the diagnosis and management of tongue lesions, from October 1993 to October 2013, were reviewed. Histological data were also obtained and blindly reexamined. Results For instance, a biopsy performed on a lingual ulcer has a strong predicting association with a carcinoma, whereas a biopsy on a white lesion predicts for a leukoplakia or oral lichen planus. Moreover, a biopsy of erosion is representative of bullous diseases, whereas a biopsy on a verrucous-papillary lesion is significant for fibroma. Furthermore, carcinomas occur in the majority of cases on the lingual edge or pelvis, oral lichen planus is mainly seen on the edge, and fibromas mostly on the lingual tip. Conclusions The high frequency of tongue involvement of such different diseases emphasizes the importance of histological characterization and that some diseases occur more frequently than others, with a peculiar clinical aspect and a more common area. In fact our survey can help the clinician in advancing diagnostic hypothesis, on the basis of the elementary lesion and its site of involvement. Key words:Tongue lesions, clinical appearance, histological description. PMID:26241456

Classification of Regional Radiographic Emphysematous Patterns Using Low-Attenuation Gap Length Matrix

NASA Astrophysics Data System (ADS)

Tan, Kok Liang; Tanaka, Toshiyuki; Nakamura, Hidetoshi; Shirahata, Toru; Sugiura, Hiroaki

The standard computer-tomography-based method for measuring emphysema uses percentage of area of low attenuation which is called the pixel index (PI). However, the PI method is susceptible to the problem of averaging effect and this causes the discrepancy between what the PI method describes and what radiologists observe. Knowing that visual recognition of the different types of regional radiographic emphysematous tissues in a CT image can be fuzzy, this paper proposes a low-attenuation gap length matrix (LAGLM) based algorithm for classifying the regional radiographic lung tissues into four emphysema types distinguishing, in particular, radiographic patterns that imply obvious or subtle bullous emphysema from those that imply diffuse emphysema or minor destruction of airway walls. Neural network is used for discrimination. The proposed LAGLM method is inspired by, but different from, former texture-based methods like gray level run length matrix (GLRLM) and gray level gap length matrix (GLGLM). The proposed algorithm is successfully validated by classifying 105 lung regions that are randomly selected from 270 images. The lung regions are hand-annotated by radiologists beforehand. The average four-class classification accuracies in the form of the proposed algorithm/PI/GLRLM/GLGLM methods are: 89.00%/82.97%/52.90%/51.36%, respectively. The p-values from the correlation analyses between the classification results of 270 images and pulmonary function test results are generally less than 0.01. The classification results are useful for a followup study especially for monitoring morphological changes with progression of pulmonary disease.

Sirtuins in dermatology: applications for future research and therapeutics.

PubMed

Serravallo, Melissa; Jagdeo, Jared; Glick, Sharon A; Siegel, Daniel M; Brody, Neil I

2013-05-01

Sirtuins are a family of seven proteins in humans (SIRT1-SIRT7) that are involved in multiple cellular processes relevant to dermatology. The role of sirtuins in other organ systems is established. However, the importance of these proteins in dermatology is less defined. Recently, sirtuins gained international attention because of their role as "longevity proteins" that may extend and enhance human life. Sirtuins function in the cell via histone deacetylase and/or adenosine diphosphate ribosyltransferase enzymatic activity that target histone and non-histone substrates, including transcription regulators, tumor suppressors, structural proteins, DNA repair proteins, cell signaling proteins, transport proteins, and enzymes. Sirtuins are involved in cellular pathways related to skin structure and function, including aging, ultraviolet-induced photoaging, inflammation, epigenetics, cancer, and a variety of cellular functions including cell cycle, DNA repair and proliferation. This review highlights sirtuin-related cellular pathways, therapeutics and pharmacological targets in atopic dermatitis, bullous dermatoses, collagen vascular disorders, psoriasis, systemic lupus erythematosus, hypertrophic and keloid scars, cutaneous infections, and non-melanoma and melanoma skin cancer. Also discussed is the role of sirtuins in the following genodermatoses: ataxia telangiectasia, Cowden's syndrome, dyskeratosis congenita, Rubenstein-Taybi, Werner syndrome, and xeroderma pigmentosum. The pathophysiology of these inherited diseases is not well understood, and sirtuin-related processes represent potential therapeutic targets for diseases lacking suitable alternative treatments. The goal of this review is to bring attention to the dermatology community, physicians, and scientists, the importance of sirtuins in dermatology and provide a foundation and impetus for future discussion, research and pharmacologic discovery.

Penetrating Keratoplasty at a Tertiary Referral Center in Ethiopia: Indications and Outcomes.

PubMed

Ayalew, Menen; Tilahun, Yonas; Holsclaw, Doug; Indaram, Maanasa; Stoller, Nicole E; Keenan, Jeremy D; Rose-Nussbaumer, Jennifer

2017-06-01

To describe the indications, visual acuity outcomes, and graft survival after penetrating keratoplasty (PKP) in Addis Ababa, Ethiopia. The medical records of patients who underwent PKP at Menelik II Hospital between September 2000 and September 2013 were retrospectively reviewed. The prespecified outcomes were graft survival, visual acuity, and complication rates. A total of 321 patients underwent PKP during the study period and were included in the analysis. Indications for surgery were trachoma or leukoma in 141 (44%), keratoconus in 45 (14%), corneal dystrophy in 46 (14%), pseudophakic or aphakic bullous keratopathy in 28 (9%), trauma in 27 (8%), previous graft failure in 18 (6%), active ulcer, burn, or perforation in 9 (3%), and others in 7 (2%). The graft survival rate was 80% overall at 2 years but varied considerably depending on the indication for surgery. Uncorrected visual acuity improved from baseline mean logarithm of the minimum angle of resolution 2.09 (SD 0.67) to mean logarithm of the minimum angle of resolution of 1.53 (SD 1.03) at 2 years. A number of factors affected the visual acuity outcomes. Patients were not routinely refracted, and only 18% (N = 60) of patients had access to corrective spectacles or contact lenses postoperatively. Complication rates were high with infectious keratitis being the most common. PKP is becoming a viable treatment for corneal opacity in developing countries. However, the high burden of disease and lack of corrective lenses remain significant obstacles to overcome.

R213W mutation in the retinoschisis 1 gene causes X-linked juvenile retinoschisis in a large Chinese family.

PubMed

Xu, Jun; Gu, Hong; Ma, Kai; Liu, Xipu; Snellingen, Torkel; Sun, Erdan; Wang, Ningli; Liu, Ningpu

2010-08-12

We identified a large Chinese family with X-linked juvenile retinoschisis. The purpose of this study was to report the clinical findings of the family and to identify the genetic mutation by screening the retinoschisis 1 (RS1) gene. Family history was collected and all family members underwent routine ophthalmic examination. Venous blood was collected from family members and genomic DNA was extracted. The exons of RS1 were screened by PCR followed by direct sequencing and/or restriction enzyme digestion. The pedigree of interest was a four-generation family with 52 family members, including seven affected individuals. The proband was a 5-year-old boy showing highly elevated bullous retinoschisis with moderate vitreous hemorrhage in both eyes. Vitrectomy was performed in the left eye of the proband. Five affected males showed large peripheral retinoschisis in both eyes, either involving the macula or combined with foveal stellate cystic change. One of the affected family members showed only a foveal stellate cystic change in both eyes without periphery retinoschisis. Visual acuity of affected individuals ranged from hand motion to 0.4. The R213W mutation in exon 6 of RS1 was identified in all affected individuals, predicting an amino acid substitution of arginine to tryptophan at codon 213. Our data show that the R213W mutation in RS1 causes various severities of retinoschisis in a large Chinese family, providing further evidence for X-linked juvenile retinoschisis phenotypic variability.

Temporal course of avascular femoral head necrosis in patients with pemphigus vulgaris.

PubMed

Balighi, Kamran; Daneshpazhooh, Maryam; Aghazadeh, Nessa; Saeidi, Vahide; Shahpouri, Farzam; Hejazi, Pardis; Chams-Davatchi, Cheyda

2016-10-01

Pemphigus vulgaris (PV) is typically treated with systemic corticosteroids and immunosuppressive agents. Avascular necrosis (AVN) of the femoral head is a well-recognized major complication of corticosteroid therapy. The characteristics of this serious complication in PV remain unknown. Uncontrolled, retrospective study of all PV-related AVN cases diagnosed at an Iranian autoimmune bullous disease clinic between 1985 and 2013. Of the 2,321 medical records of PV patients reviewed, 45 (1.93 %) cases showed femoral AVN, with 30 (66.7 %) individuals being male. The mean age at diagnosis of AVN was 47.4 ± 14.2 years. The mean interval between the diagnosis of PV and the onset of AVN was 25.3 ± 18.3 months. With the exception of eight cases (17.8 %), the majority of patients developed AVN within three years after the diagnosis of PV. The mean cumulative dose of prednisolone in patients with AVN was 13,115.8 ± 7041.1 mg. There was a strong correlation between the total prednisolone dose and the time of onset of AVN (p = 0.001). In patients with a history of alendronate intake, that interval was significantly shorter (p = 0.01). Occurring in about 2 % of patients, AVN is a serious complication of corticosteroid treatment in patients with PV, predominantly in the first three years of treatment. In individuals receiving higher doses of prednisolone, AVN tends to occur earlier. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Skin rash and arthritis a simplified appraisal of less common associations.

PubMed

Cozzi, A; Doria, A; Gisondi, P; Girolomoni, G

2014-06-01

Skin and joint manifestations are part of the clinical spectrum of many disorders. Well-known associations include psoriatic arthritis and arthritis associated with autoimmune connective tissue diseases. This review focuses on less common associations where skin lesions can provide easily accessible and valuable diagnostic clues, and directly lead to the specific diagnosis or limit the list of possibilities. This may also affect health care resources as diagnostic tests are often low-specific, highly expensive and poorly available. This group of diseases can be divided into two subsets, based on the presence/absence of fever, and then further classified according to elementary skin lesions (macular, urticarial, maculo-papular, vesico-bullous, pustular, petechial and nodular). In most instances joint involvement occurs as peripheral migrating polyarthritis. Erythematosus macular or urticarial rashes occur in most febrile disorders such as monogenic autoinflammatory syndromes, Schnitzler's syndrome, Still's disease and rheumatic fever and afebrile diseases as urticarial vasculitis. Pustular rash may be observed in chronic recurrent multifocal osteomyelitis (CRMO) and pyogenic arthritis with pyoderma gangrenosum and acne (PAPA) syndrome (both febrile) as well as in Behcet's disease and Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome (both non-febrile). Papular lesions are typical of secondary syphilis, sarcoidosis, interstitial granulomatous dermatitis, papular petechial of cutaneous small-vessel vasculitis and nodular lesions of polyarteritis nodosa and multicentric reticulohistiocytosis all of which are afebrile. Differential diagnosis includes infections and drug reactions which may mimic several of these conditions. To biopsy the right skin lesion at the right time it is essential to obtain relevant histological information. © 2013 European Academy of Dermatology and Venereology.

A combined pulmonary-radiology workshop for visual evaluation of COPD: study design, chest CT findings and concordance with quantitative evaluation.

PubMed

Barr, R Graham; Berkowitz, Eugene A; Bigazzi, Francesca; Bode, Frederick; Bon, Jessica; Bowler, Russell P; Chiles, Caroline; Crapo, James D; Criner, Gerard J; Curtis, Jeffrey L; Dass, Chandra; Dirksen, Asger; Dransfield, Mark T; Edula, Goutham; Erikkson, Leif; Friedlander, Adam; Galperin-Aizenberg, Maya; Gefter, Warren B; Gierada, David S; Grenier, Philippe A; Goldin, Jonathan; Han, MeiLan K; Hanania, Nicola A; Hansel, Nadia N; Jacobson, Francine L; Kauczor, Hans-Ulrich; Kinnula, Vuokko L; Lipson, David A; Lynch, David A; MacNee, William; Make, Barry J; Mamary, A James; Mann, Howard; Marchetti, Nathaniel; Mascalchi, Mario; McLennan, Geoffrey; Murphy, James R; Naidich, David; Nath, Hrudaya; Newell, John D; Pistolesi, Massimo; Regan, Elizabeth A; Reilly, John J; Sandhaus, Robert; Schroeder, Joyce D; Sciurba, Frank; Shaker, Saher; Sharafkhaneh, Amir; Silverman, Edwin K; Steiner, Robert M; Strange, Charlton; Sverzellati, Nicola; Tashjian, Joseph H; van Beek, Edwin J R; Washington, Lacey; Washko, George R; Westney, Gloria; Wood, Susan A; Woodruff, Prescott G

2012-04-01

The purposes of this study were: to describe chest CT findings in normal non-smoking controls and cigarette smokers with and without COPD; to compare the prevalence of CT abnormalities with severity of COPD; and to evaluate concordance between visual and quantitative chest CT (QCT) scoring. Volumetric inspiratory and expiratory CT scans of 294 subjects, including normal non-smokers, smokers without COPD, and smokers with GOLD Stage I-IV COPD, were scored at a multi-reader workshop using a standardized worksheet. There were 58 observers (33 pulmonologists, 25 radiologists); each scan was scored by 9-11 observers. Interobserver agreement was calculated using kappa statistic. Median score of visual observations was compared with QCT measurements. Interobserver agreement was moderate for the presence or absence of emphysema and for the presence of panlobular emphysema; fair for the presence of centrilobular, paraseptal, and bullous emphysema subtypes and for the presence of bronchial wall thickening; and poor for gas trapping, centrilobular nodularity, mosaic attenuation, and bronchial dilation. Agreement was similar for radiologists and pulmonologists. The prevalence on CT readings of most abnormalities (e.g. emphysema, bronchial wall thickening, mosaic attenuation, expiratory gas trapping) increased significantly with greater COPD severity, while the prevalence of centrilobular nodularity decreased. Concordances between visual scoring and quantitative scoring of emphysema, gas trapping and airway wall thickening were 75%, 87% and 65%, respectively. Despite substantial inter-observer variation, visual assessment of chest CT scans in cigarette smokers provides information regarding lung disease severity; visual scoring may be complementary to quantitative evaluation.

Anti-desmoglein 1 antibodies in Tunisian healthy subjects: arguments for the role of environmental factors in the occurrence of Tunisian pemphigus foliaceus

PubMed Central

KALLEL SELLAMI, M; BEN AYED, M; MOUQUET, H; DROUOT, L; ZITOUNI, M; MOKNI, M; CERRUTI, M; TURKI, H; FEZZA, B; MOKHTAR, I; BEN OSMAN, A; ZAHAF, A; KAMOUN, M R; JOLY, P; MASMOUDI, H; MAKNI, S; TRON, F; GILBERT, D

2004-01-01

Pemphigus foliaceus is an autoimmune blistering skin disease mediated by autoantibodies directed against desmoglein 1 and occurs as a sporadic form throughout the world, or as an endemic form called fogo selvagem in Brazil. Healthy subjects living in Brazilian endemic areas produce antidesmoglein 1 antibodies, suggesting the role of environmental factors in the initiation of the autoimmune response. Tunisia was described recently as an endemic area where the disease is characterized by its high rate among young people, especially women. An enzyme-linked immunosorbent assay using recombinant desmoglein 1 as antigen was used to detect antibodies against desmoglein 1 and calibrated with sera from 67 French healthy blood donors, 20 French pemphigus foliaceus patients and patients with other bullous skin diseases. When sera from 179 healthy Tunisian blood donors were tested, 31 (17%) were found positive. The desmoglein 1 binding activity of these 31 sera was confirmed in 10 cases by indirect immunofluorescence analysis and/or immunoblotting using human epidermal extract. Subclass analysis of antidesmoglein 1 antibodies showed that they were almost exclusively of the IgG2 subclass in positive normal sera and of IgG4 subclass in patients with PF. Thus, antibodies against desmoglein 1 are prevalent in normal subjects living in Tunisia which, along with their IgG2 isotype, suggests the role of the environment in the pathogenesis of this endemic type of pemphigus foliaceus and the need for additional factors to switch from a subclinical to a clinical form of the disease. PMID:15196262

Community-acquired necrotizing fasciitis caused by Acinetobacter calcoaceticus: a case report and literature review.

PubMed

Nonaka, Yuko; Nagae, Masaaki; Omae, Takahito; Yamamoto, Shuhei; Horitani, Ryosuke; Maeda, Daigen; Yoshinaga, Takayuki

2014-05-01

A 61-year-old man presented with pain in the abdomen and right lower limb. He had a history of hepatitis B virus-induced liver cirrhosis, but had not been visiting the outpatient clinic and did not receive any medication. Cutaneous necrosis and bulla were observed on his abdomen and right lower limb. The necrotic skin was incised, and he was diagnosed with necrotizing fasciitis. A nonfermentative Gram-negative bacillus infection was confirmed from aspirated fluid and blood cultures. Therefore, meropenem and immunoglobulins were administered. Because necrosis was widespread, surgical debridement was performed. Thereafter, Acinetobacter calcoaceticus infection was confirmed by semi-quantitative PCR using the bullous fluid and blood cultures. Meropenem was administered for 3 weeks, followed by levofloxacin alone for 1 week. The patient's condition improved; therefore, skin grafting was performed as planned and yielded a favorable response. After rehabilitation, the patient could walk without support and infection did not recur. However, he had severe liver cirrhosis and large esophageal varices, and he eventually died from sudden varix rupture. Necrotizing fasciitis is an uncommon soft tissue infection, associated with high morbidity and mortality, and early recognition and treatment are crucial for survival. Acinetobacter is rarely associated with necrotizing fasciitis. Although this is a very rare case of the occurrence of necrotizing fasciitis due to A. calcoaceticus infection, we believe that this organism can be pathogenic in immunocompromised patients such as those with liver cirrhosis by reporting this case. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Descemet Stripping Automated Endothelial Keratoplasty for Failed Penetrating Keratoplasty: Influence of the Graft-Host Junction on the Graft Survival Rate.

PubMed

Omoto, Takashi; Sakisaka, Toshihiro; Toyono, Tetsuya; Yoshida, Junko; Shirakawa, Rika; Miyai, Takashi; Yamagami, Satoru; Usui, Tomohiko

2018-04-01

To investigate the clinical results of Descemet stripping automated endothelial keratoplasty (DSAEK) for failed penetrating keratoplasty (PK) and the influence of the graft-host junction (GHJ) on the graft survival rate. Data were retrospectively collected on patient demographics, visual outcomes, complications, and graft survival rate for 17 eyes of 16 patients who underwent DSAEK for failed PK. The graft survival rate was compared between the eyes when divided into a bump group and a well-aligned group according to the shape of the GHJ detected on anterior segment optical coherence tomography. The most common indication for initial PK was bullous keratopathy after glaucoma surgery (35.3%). Seven eyes (41.2%) were classified into the bump group and 10 eyes (58.8%) into the well-aligned group. The mean best-ever documented visual acuity (BDVA) after DSAEK was 0.33 logMAR. Postoperatively, almost 70% of eyes achieved a BDVA that was within 0.2 logMAR of their preoperative BDVA. Graft detachment occurred in 29.4% of eyes and primary graft failure in 17.6%. All primary failures occurred in the bump group. The cumulative graft survival rate was 82.3% at 1 year, 73.2% at 2 years, and 58.6% at 3 years. Graft failure was more likely in eyes in the bump group than in those in the well-aligned group (P = 0.037, Wilcoxon test). DSAEK for failed PK had a favorable outcome in this study. However, the GHJ should be assessed carefully before performing the procedure.

Drug-induced lupus erythematosus.

PubMed

Marzano, A V; Tavecchio, S; Menicanti, C; Crosti, C

2014-06-01

Drug-induced lupus erythematosus (DI-LE) is defined as an entity characterized by clinical manifestations and immunopathological serum findings similar to those of idiopathic lupus but which is temporally related to drug exposure and resolves after withdrawal of the implicated drug. Similarly to idiopathic lupus, DI-LE can be divided into systemic LE, subacute cutaneous LE (SCLE), chronic cutaneous LE (CCLE) and cutaneous LE tumidus. DI-SCLE is the most frequent variant of drug-induced cutaneous LE and presents mainly with annular-polycyclic lesions; the clinical picture is often widespread, with involvement of the lower legs that are usually spared in idiopathic SCLE. ANA and anti-Ro/SSA antibodies are typically present, whereas antihistone antibodies are uncommonly found. We have recently addressed the question whether DI-SCLE differs significantly from its idiopathic counterpart by virtue of clinical features and, based on our findings, we have suggested that the frequent occurrence of malar rash and bullous, erythema multiforme-like and vasculitic manifestations can be regarded as the hallmark of DI-SCLE. In contrast, the histology is not a useful diagnostic criterion for DI-SCLE, considering that the typical pattern of lichenoid interface dermatitis is seen only in the early stage of disease and tissue eosinophilia does not represent a differentiating histopathological feature. DI-CCLE and DI-LE tumidus, albeit possibly misdiagnosed, are rarely observed and are characterized by classic discoid lesions and erythematous-oedematous plaques on sun exposed areas, respectively. Management of DI-LE is based on the discontinuation of the offending drug; topical and/or systemic corticosteroids and other immunomodulating/immunosuppressive agents should be reserved for resistant cases.

Anaphylactoid reaction in a heartworm-infected dog undergoing lung lobectomy.

PubMed

Carter, Jennifer E; Chanoit, Guillaume; Kata, Cheryl

2011-05-15

A 7-year-old 23-kg (50.6-lb) spayed female Border Collie with a history of heartworm disease was evaluated for respiratory distress. Computed tomography of the thorax revealed possible pulmonary bullae or blebs, and on the basis of these findings, a tentative diagnosis of bullous emphysema was made. Exploratory median sternotomy revealed gross pathological lesions in the right caudal lung lobe; the most peripheral portion appeared discolored (pale pink), and a clear line of demarcation was observed. Upon excision of the affected lung lobe, a worm segment was noticed both on the remaining stump of the lung lobe in the dog and in the removed lobe. At this time, the dog had an anaphylactoid reaction. The reaction was successfully treated with fluid therapy, antihistamines, and corticosteroids. Lung lobectomy of the right caudal lobe resulted in clinical resolution of the bilateral pneumothorax. However, during the postoperative period, the dog developed a hemothorax and was returned to surgery. As no obvious cause for the hemothorax was seen at the second surgery, the dog was treated for a potential coagulopathy with fresh frozen plasma, which provided clinical resolution of the hemothorax. Parasitological examination of the worm segment confirmed a Dirofilaria immitis infection. The dog was discharged 5 days after surgery and treated with doxycycline for 30 days and monthly administration of heartworm preventative was prescribed. Heartworm infection should be a differential diagnosis in dogs with spontaneous pneumothorax. Anaphylactoid reactions associated with accidental dissection of adult heartworms should be managed with treatment aimed at cardiovascular stabilization.

The combined use of surgical debulking and diode laser photocoagulation for limbal melanoma treatment: a retrospective study of 21 dogs.

PubMed

Andreani, Valentina; Guandalini, Adolfo; D'Anna, Nunzio; Giudice, Chiara; Corvi, Roberta; Di Girolamo, Nicola; Sapienza, John S

2017-03-01

To evaluate effectiveness and safety of debulking and diode laser photocoagulation (DPC) for the treatment of limbal melanoma (LM). Retrospective multi-institutional case series. Medical records of animals diagnosed with LM at the Centro Veterinario Specialistico (CVS) and at the Long Island Veterinary Specialists from 1994 to 2014 were retrieved. Signalment, location, extent of tumors, recurrence rate, and early and late complications were reported. Patient follow-up information was obtained from veterinary ophthalmologists, primary care veterinarians, and where appropriate, owners. Twenty-one eyes of 21 dogs (13 females and 8 males) were included in this study. The dogs' average age was 6 years (range: 7 months-11 years). The follow-up period ranged from 1-108 months (median 48 months) after the last DPC procedure. Long-term follow-up was obtained by telephone interviews in 6 of 20 cases and by clinical re-evaluations in 14 of 20 cases. The most common early complications were a moderate anterior uveitis and peripheral corneal edema (21/21 eyes). Late complications included corneal fibrosis and/or pigmentation (20/21). In one case, a severe bullous keratopathy associated with extensive corneal fibrosis was observed (1/21). One case was blind due to concurrent Sudden Acquired Retinal Degeneration (SARD). However, after surgery 2 of 20 eyes lost vision and one of these was enucleated. Debulking, in addition to diode laser photocoagulation, was technically straightforward to perform, minimally invasive, well tolerated, and highly successful in this case series. © 2016 American College of Veterinary Ophthalmologists.

Marijuana and Lung Disease.

PubMed

Tashkin, Donald P

2018-05-17

As marijuana smoking prevalence increases in the U.S. concern regarding its potential risks to lung health has also risen, given the general similarity in the smoke contents between marijuana and tobacco. Most studies have found a significant association between marijuana smoking and chronic bronchitis symptoms after adjustment for tobacco. While reports are mixed regarding associations between marijuana smoking and lung function, none has shown a relationship to decrements in forced expired volume in 1 sec (FEV1) and few have found a relationship to a decreased ratio of FEV1 to forced vital capacity (FVC), possibly related to an association between marijuana and an increased FVC. A few studies have found a modest reduction in specific airway conductance in relation to marijuana, probably reflecting endoscopic evidence of bronchial mucosal edema among habitual marijuana smokers. Diffusing capacity in marijuana smokers has been normal and two studies of thoracic high-resolution computed tomography (HRCT) have not shown any association of marijuana smoking with emphysema. Although bronchial biopsies from habitual marijuana smokers have shown precancerous histopathological changes, a large cohort study and a pooled analysis of six well-designed case-control studies have not found evidence of a link between marijuana smoking and lung cancer. The immunosuppressive effects of delta-9 tetrahydrocannabinol raise the possibility of an increased risk of pneumonia, but further studies are needed to evaluate this potential risk. Several cases series have demonstrated pneumothoraces/pneumomediastinum, as well as bullous lung disease, in marijuana smokers, but these associations require epidemiologic studies for firmer evidence of possible causality. Copyright © 2018. Published by Elsevier Inc.

R213W mutation in the retinoschisis 1 gene causes X-linked juvenile retinoschisis in a large Chinese family

PubMed Central

Xu, Jun; Gu, Hong; Ma, Kai; Liu, Xipu; Snellingen, Torkel; Sun, Erdan; Wang, Ningli

2010-01-01

Purpose We identified a large Chinese family with X-linked juvenile retinoschisis. The purpose of this study was to report the clinical findings of the family and to identify the genetic mutation by screening the retinoschisis 1 (RS1) gene. Methods Family history was collected and all family members underwent routine ophthalmic examination. Venous blood was collected from family members and genomic DNA was extracted. The exons of RS1 were screened by PCR followed by direct sequencing and/or restriction enzyme digestion. Results The pedigree of interest was a four-generation family with 52 family members, including seven affected individuals. The proband was a 5-year-old boy showing highly elevated bullous retinoschisis with moderate vitreous hemorrhage in both eyes. Vitrectomy was performed in the left eye of the proband. Five affected males showed large peripheral retinoschisis in both eyes, either involving the macula or combined with foveal stellate cystic change. One of the affected family members showed only a foveal stellate cystic change in both eyes without periphery retinoschisis. Visual acuity of affected individuals ranged from hand motion to 0.4. The R213W mutation in exon 6 of RS1 was identified in all affected individuals, predicting an amino acid substitution of arginine to tryptophan at codon 213. Conclusions Our data show that the R213W mutation in RS1 causes various severities of retinoschisis in a large Chinese family, providing further evidence for X-linked juvenile retinoschisis phenotypic variability. PMID:20806044

Long-term Rebamipide and Diquafosol in Two Cases of Immune-Mediated Dry Eye

PubMed Central

Yamane, Mio; Ogawa, Yoko; Fukui, Masaki; Kamoi, Mizuka; Saijo-Ban, Yumiko; Yaguchi, Saori; Mukai, Shin; Kawakita, Tetsuya; Simmura, Shigeto; Tsubota, Kazuo

2015-01-01

ABSTRACT Purpose Two new drugs with mucin-inducing and secretion-promotive effects, rebamipide and diquafosol, were recently approved as topical dry-eye treatments. We report two cases in which the long-term use of mucin-inducing eye drops improved chronic ocular graft-versus-host disease (cGVHD)–related dry eye and ocular cicatricial pemphigoid (OCP)-like disease. Case Reports Case 1. A 61-year-old woman had cGVHD-related dry eye that resisted traditional medications. Next, we use topical diquafosol in addition to conventional treatments. The patient used diquafosol for 6 months without experiencing any side effects. The symptoms, including dry-eye sensation, ocular pain, foreign body sensation, and photophobia, as well as ocular surface findings including fluorescein and rose bengal scores and tear break-up time (TBUT), partly improved. To further improve the clinical signs and symptoms and decrease chronic inflammation, rebamipide was added to diquafosol. The symptoms, TBUT, and fluorescein and rose bengal scores markedly improved after long-term dual treatment without any side effects for 6 months. Case 2. A 77-year-old woman had OCP-like disease with dry eye. The patient did not improve using the currently available conventional treatments. Next, we use topical rebamipide in addition to conventional treatments. Symptoms including asthenopia, dry-eye sensation, ocular pain, and dull sensation, as well as fluorescein and rose bengal scores and TBUT, partly improved. Specifically, functional visual acuity was markedly improved after commencement of rebamipide. To further improve the clinical signs and symptoms and increase tear film stability and tear film volume, diquafosol was added to rebamipide. The combination of diquafosol and rebamipide worked for the patient. Improvements were seen in several symptoms, fluorescein and rose bengal scores, Schirmer test value, and TBUT without any side effects for 12 months. Conclusions Long-term treatment with topical rebamipide and diquafosol can improve dry eye in patients with cGVHD or OCP-like disease. PMID:25785527

Long-term rebamipide and diquafosol in two cases of immune-mediated dry eye.

PubMed

Yamane, Mio; Ogawa, Yoko; Fukui, Masaki; Kamoi, Mizuka; Saijo-Ban, Yumiko; Yaguchi, Saori; Mukai, Shin; Kawakita, Tetsuya; Simmura, Shigeto; Tsubota, Kazuo

2015-04-01

Two new drugs with mucin-inducing and secretion-promotive effects, rebamipide and diquafosol, were recently approved as topical dry-eye treatments. We report two cases in which the long-term use of mucin-inducing eye drops improved chronic ocular graft-versus-host disease (cGVHD)-related dry eye and ocular cicatricial pemphigoid (OCP)-like disease. Case 1. A 61-year-old woman had cGVHD-related dry eye that resisted traditional medications. Next, we use topical diquafosol in addition to conventional treatments. The patient used diquafosol for 6 months without experiencing any side effects. The symptoms, including dry-eye sensation, ocular pain, foreign body sensation, and photophobia, as well as ocular surface findings including fluorescein and rose bengal scores and tear break-up time (TBUT), partly improved. To further improve the clinical signs and symptoms and decrease chronic inflammation, rebamipide was added to diquafosol. The symptoms, TBUT, and fluorescein and rose bengal scores markedly improved after long-term dual treatment without any side effects for 6 months. Case 2. A 77-year-old woman had OCP-like disease with dry eye. The patient did not improve using the currently available conventional treatments. Next, we use topical rebamipide in addition to conventional treatments. Symptoms including asthenopia, dry-eye sensation, ocular pain, and dull sensation, as well as fluorescein and rose bengal scores and TBUT, partly improved. Specifically, functional visual acuity was markedly improved after commencement of rebamipide. To further improve the clinical signs and symptoms and increase tear film stability and tear film volume, diquafosol was added to rebamipide. The combination of diquafosol and rebamipide worked for the patient. Improvements were seen in several symptoms, fluorescein and rose bengal scores, Schirmer test value, and TBUT without any side effects for 12 months. Long-term treatment with topical rebamipide and diquafosol can improve dry eye in patients with cGVHD or OCP-like disease.

Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis.

PubMed

Meager, A; Wadhwa, M; Dilger, P; Bird, C; Thorpe, R; Newsom-Davis, J; Willcox, N

2003-04-01

We have screened for spontaneous anticytokine autoantibodies in patients with infections, neoplasms and autoimmune diseases, because of their increasingly reported co-occurrence. We tested for both binding and neutralizing autoantibodies to a range of human cytokines, including interleukin-1alpha (IL-1alpha), IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, interferon-alpha2 (IFN-alpha2), IFN-omega, IFN-beta, IFN-gamma, tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta1) and granulocyte-macrophage colony stimulating factor (GM-CSF), in plasmas or sera. With two notable exceptions described below, we found only occasional, mostly low-titre, non-neutralizing antibodies, mainly to GM-CSF; also to IL-10 in pemphigoid. Strikingly, however, high-titre, mainly IgG, autoantibodies to IFN-alpha2, IFN-omega and IL-12 were common at diagnosis in patients with late-onset myasthenia gravis (LOMG+), thymoma (T) but no MG (TMG-) and especially with both thymoma and MG together (TMG+). The antibodies recognized other closely related type I IFN-alpha subtypes, but rarely the distantly related type I IFN-beta, and never (detectably) the unrelated type II IFN-gamma. Antibodies to IL-12 showed a similar distribution to those against IFN-alpha2, although prevalences were slightly lower; correlations between individual titres against each were so modest that they appear to be entirely different specificities. Neither showed any obvious correlations with clinical parameters including thymoma histology and HLA type, but they did increase sharply if the tumours recurred. These antibodies neutralized their respective cytokine in bioassays in vitro; although they persisted for years severe infections were surprisingly uncommon, despite the immunosuppressive therapy also used in most cases. These findings must hold valuable clues to autoimmunizing mechanisms in paraneoplastic autoimmunity.

Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure.

PubMed

Massie, Isobel; Dale, Sarah B; Daniels, Julie T

2015-06-01

Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE- RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP.

Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure

PubMed Central

Dale, Sarah B.; Daniels, Julie T.

2015-01-01

Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE− RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP. PMID:25380529

Trends in the distribution of donor corneal tissue and indications for corneal transplantation: the New Zealand National Eye Bank Study 2000-2009.

PubMed

Cunningham, William J; Brookes, Nigel H; Twohill, Helen C; Moffatt, S Louise; Pendergrast, David G C; Stewart, Joanna M; McGhee, Charles N J

2012-03-01

To investigate the indications for corneal transplantation and the distribution of donor corneal tissue in New Zealand. Analysis of the prospective database of the New Zealand National Eye Bank. A total of 2205 corneal transplants were assessed. New Zealand National Eye Bank records were analysed for the decade 2000-2009. Variables analysed included donor corneal tissue distribution (including public and private sectors), indications for transplantation, donor corneal tissue recipient demographics (age and gender) and corneal transplantation type. An average of 220 corneal transplants were performed each year over the 10-year period (n=2205). The median recipient age was 45years (range 3 to 102years) and 54.0% of recipients were male. In total 71.8% of transplants were performed in the public health sector. Surgeons in the Auckland metropolitan area performed 47.2% of all corneal transplants. The most common indications for corneal transplantation were: keratoconus (41.1%), repeat transplant (17.0%), aphakic/pseudophakic bullous keratopathy (13.9%), corneal dystrophy (10.7%), keratitis (7.9%) and trauma (3.7%). Overall, penetrating keratoplasty accounted for 90.7% of all corneal transplants, however, during the latter half of the study there was a progressive shift in transplantation type, with deep anterior lamellar keratoplasty and Descemet's stripping endothelial keratoplasty combined accounting for 32.3% of all transplants in the final year of the study period. This New Zealand National Eye Bank study provides valuable data regarding the indications for corneal transplantation, transplant recipient demographics and changes in transplantation type in New Zealand over the past decade. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

Increased risk of stroke in contact dermatitis patients

PubMed Central

Chang, Wei-Lun; Hsu, Min-Hsien; Lin, Cheng-Li; Chan, Po-Chi; Chang, Ko-Shih; Lee, Ching-Hsiao; Hsu, Chung-Yi; Tsai, Min-Tein; Yeh, Chung-Hsin; Sung, Fung-Chang

2017-01-01

Abstract Dermatologic diseases are not traditional risk factors of stroke, but recent studies show atopic dermatitis, psoriasis, and bullous skin disease may increase the risk of stroke and other cardiovascular diseases. No previous studies have focused on the association between contact dermatitis and stroke. We established a cohort comprised of 48,169 contact dermatitis patients newly diagnosed in 2000–2003 and 96,338 randomly selected subjects without the disorder, frequency matched by sex, age, and diagnosis year, as the comparison cohort. None of them had a history of stroke. Stroke incidence was assessed by the end of 2011 for both cohorts. The incidence stroke was 1.1-fold higher in the contact dermatitis cohort than in the comparison cohort (5.93 vs 5.37 per 1000 person-years, P < 0.01). The multivariable Cox method analyzed adjusted hazard ratios (aHRs) were 1.12 (95% confidence interval [CI], 1.05–1.19) for all stroke types and 1.12 (95% CI, 1.05–1.20) for ischemic stroke and 1.11 (95% CI, 0.94–1.30) for hemorrhagic stroke. The age-specific aHR of stroke for contact dermatitis cohort increased with age, from 1.14 (95% CI, 1.03–1.27) for 65 to 74 years; to 1.27 (95% CI, 1.15–1.42) for 75 years and older. The aHR of stroke were 1.16 (95% CI, 1.07–1.27) and 1.09 (95% CI, 1.00–1.18) for men and women, respectively. This study suggests that patients with contact dermatitis were at a modestly increased risk of stroke, significant for ischemic stroke but not for hemorrhagic stroke. Comorbidity, particularly hypertension, increased the hazard of stroke further. PMID:28272195

Epidemiology of Systemic Lupus Erythematosus and Cutaneous Lupus in a Predominantly White Population in the United States

PubMed Central

Jarukitsopa, Sudumpai; Hoganson, Deana D; Crowson, Cynthia S; Sokumbi, Olayemi; Davis, Mark D; Michet, Clement J; Matteson, Eric L; Maradit –Kremers, Hilal; Chowdhary, Vaidehi R

2014-01-01

Objective Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993 to 2005. Methods SLE cases were identified from review of medical records and fulfilled the 1982 ACR classification criteria. CLE cases included patients with classic discoid LE (CDLE), subacute cutaneous LE (SCLE), lupus panniculitis and bullous LE. Age-and sex-adjusted incidence and prevalence were standardized to 2000 US white population. Results The age- and sex-adjusted incidence of SLE (2.9 per 100,000; 95% CI 2.0, 3.7) was similar to that of CLE (4.2 per 100,000; 95% CI 3.1, 5.2, p= 0.10). However, incidence of CLE was three times higher than SLE in males (2.4 versus 0.8 per 100,000, p=0.009). The age- and sex-adjusted prevalence of CLE on January 1, 2006 was higher than that of SLE (70.4 versus 30.5 per 100,000; p<0.001). The prevalence of CLE and SLE in women were similar but the CLE prevalence was higher in men than in women (56.9 versus 1.6 per 100,000, p<0.001). The incidence of CLE rose steadily with age and peaked at 60-69 years. Conclusion The incidences of CLE and SLE are similar but CLE is more common than SLE in males and in older adults. These findings may reflect differences in genetic or environmental etiology of CLE. PMID:25369985

Epidemiology of systemic lupus erythematosus and cutaneous lupus erythematosus in a predominantly white population in the United States.

PubMed

Jarukitsopa, Sudumpai; Hoganson, Deana D; Crowson, Cynthia S; Sokumbi, Olayemi; Davis, Mark D; Michet, Clement J; Matteson, Eric L; Maradit Kremers, Hilal; Chowdhary, Vaidehi R

2015-05-01

Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993-2005. SLE cases were identified from review of medical records and fulfilled the 1982 American College of Rheumatology classification criteria. CLE cases included patients with classic discoid lupus erythematosus, subacute CLE, lupus panniculitis, and bullous lupus erythematosus. Age- and sex-adjusted incidence and prevalence were standardized to the 2000 US white population. The age- and sex-adjusted incidence of SLE (2.9 per 100,000; 95% confidence interval [95% CI] 2.0-3.7) was similar to that of CLE (4.2 per 100,000; 95% CI 3.1-5.2, P = 0.10). However, the incidence of CLE was 3 times higher than SLE in men (2.4 versus 0.8 per 100,000; P = 0.009). The age- and sex-adjusted prevalence of CLE on January 1, 2006 was higher than that of SLE (70.4 versus 30.5 per 100,000; P < 0.001). The prevalences of CLE and SLE in women were similar, but the prevalence of CLE was higher in men than in women (56.9 versus 1.6 per 100,000; P < 0.001). The incidence of CLE rose steadily with age and peaked at 60-69 years. The incidences of CLE and SLE are similar, but CLE is more common than SLE in men and in older adults. These findings may reflect differences in genetic or environmental etiology of CLE. © 2015, American College of Rheumatology.

Management of postkeratoplasty astigmatism by paired arcuate incisions with compression sutures.

PubMed

Fares, Usama; Mokashi, Aashish A; Al-Aqaba, Mouhamed Ali; Otri, Ahmad Muneer; Miri, Ammar; Dua, Harminder Singh

2013-04-01

To analyse the efficacy of paired arcuate incisions and compression sutures technique in the management of post penetrating keratoplasty (PK) astigmatism. A paired arcuate incision with compression sutures procedure was used to treat 26 eyes with post-PK astigmatism ranging from 6.00 to 16.50 dioptres (D). The incisions were placed at the 7.0 mm optical zone inside the graft-host junction at a depth of 80% of corneal thickness. A 45° paired arc length was planned for eyes with preoperative astigmatism between 6D and 9D, and a 60° paired arc length was planned for eyes with preoperative astigmatism of >9D. At 3 months, corneal topography and refraction was performed and suture(s) removed if indicated. Net and vector astigmatism changes were calculated to determine the efficacy of the procedure. The indications for PK included keratoconus, Fuch's endothelial dystrophy, pseudophakic bullous keratopathy and corneal scar. There was a statistically significant reduction in the mean magnitude of astigmatism from 9.66 ± 2.90D preoperatively to 4.37 ± 2.53D postoperatively in the whole group. The mean decrease in the astigmatism was 4.37 ± 2.05D (58.4%) and 6.23 ± 3.63D (52.6%) in patients with 6-9D and >9D, respectively. Vector power calculations also showed a significant astigmatism reduction in all groups. The safety and efficacy indices were 1.40 and 0.28, respectively. Manual astigmatic keratotomy is a viable technique with relatively good safety and efficacy outcomes. Based on the results we propose that increasing the arc length to a minimum of 60° for astigmatism of 6-9D, and to 75° for astigmatism >9D, is likely to have a greater beneficial effect.

The clinical outcomes of surgical management of anterior chamber migration of a dexamethasone implant (Ozurdex®).

PubMed

Kang, Hyunseung; Lee, Min Woo; Byeon, Suk Ho; Koh, Hyoung Jun; Lee, Sung Chul; Kim, Min

2017-09-01

Our purpose was to describe the clinical course, and individualized management approaches, of patients with migration of a dexamethasone implant into the anterior chamber. This was a retrospective review of four patients with seven episodes of anterior chamber migration of a dexamethasone implant. After 924 intravitreal dexamethasone injections, anterior migration of the implant occurred in four eyes of four patients (0.43%). All four eyes were pseudophakic: one eye had a posterior chamber intraocular lens in the capsular bag but in a post-laser posterior capsulotomy state, two eyes had a sulcus intraocular lens (IOL), and one eye had an iris-fixated retropupillary IOL. All eyes had a prior vitrectomy and no lens capsule. The time interval from injection to detection of the implant migration ranged from 2 to 6 weeks. Of the four eyes with corneal edema, only one eye required a corneal transplantation, although it was unclear whether the implant migration was the direct cause of the corneal decompensation because the patient had a history of bullous keratopathy resulting from an extended history of uveitis. All patients underwent surgical intervention: two patients with a repositioning procedure, and the other two patients with removal due to repeated episodes, although surgical removal was not always necessary to reverse the corneal complications. In our study, not all patients required surgical removal of the implants. Repositioning the implant back into the vitreous cavity may be considered as an option in cases involving the first episode with no significant corneal endothelial decompensation. Considering potential anterior segment complications and the loss of drug effectiveness together, an individualized approach is recommended to obtain the best treatment outcomes and to minimize the risk of corneal complications.

Sulfur Hexafluoride 20% Versus Air 100% for Anterior Chamber Tamponade in DMEK: A Meta-Analysis.

PubMed

Marques, Raquel Esteves; Guerra, Paulo Silva; Sousa, David Cordeiro; Ferreira, Nuno Pinto; Gonçalves, Ana Inês; Quintas, Ana Miguel; Rodrigues, Walter

2018-06-01

To compare intracameral 20% sulfur hexafluoride (SF6) versus 100% air as tamponade for graft attachment in Descemet membrane endothelial keratoplasty (DMEK). Using an electronic database search on MEDLINE and CENTRAL from inception to December 2017, we performed a literature review and meta-analysis including all comparative studies of SF6 at a 20% concentration (20% SF6) versus pure air (100% air) for anterior chamber tamponade in DMEK. The primary outcome was the rebubbling rate at the final observation. The secondary outcomes were 1) the graft detachment rate, 2) mean difference (MD) in best-corrected visual acuity (BCVA), 3) manifest refraction spherical equivalent, 4) central corneal thickness (CCT), 5) percentage of endothelial cell loss (ECL), and 6) rate of pupillary block by the final observation. Statistical analysis was performed using RevMan5.3 software. Five retrospective studies were included, assessing 1195 eyes (SF6 277; air 918). The main indication for surgery was Fuchs endothelial dystrophy (SF6 85.2%; air 86.2%) and bullous keratopathy (SF6 10.8%; air 10.0%). Overall, studies were of moderate to good methodological quality. Patients in the SF6 group required 58% less rebubbling procedures (risk ratio 0.42, 95% confidence interval (CI), 0.31-0.56, P < 0.0001). No differences were found regarding BCVA improvement (MD 0.03, 95% CI, -0.05 to 0.11, P = 0.49). SF6 was associated with a minor hyperopic shift (MD 0.37 D, 95% CI, -0.95 to -0.21, P = 0.21). No differences were found regarding CCT, ECL, and rate of pupillary block (P > 0.05). In DMEK, 20% SF6 tamponade and longer postoperative time supine were associated with 58% fewer rebubbling procedures, and an ECL not statistically different from using 100% air.

Transconjunctival drainage of serous and hemorrhagic choroidal detachment.

PubMed

Rezende, Flávio A; Kickinger, Mônica C; Li, Gisèle; Prado, Renata F; Regis, Luiz Gustavo T

2012-02-01

To describe a novel surgical technique for drainage of bullous serous and hemorrhagic choroidal detachments. A prospective, consecutive case series of 6 eyes with serous and/or hemorrhagic choroidal detachments secondary to intraocular surgery was documented to evaluate the feasibility of using the 25-gauge and 20-gauge transconjunctival trocar/cannula systems to drain choroidal detachments. Two eyes had expulsive hemorrhagic choroidal detachments and 4 eyes had serous choroidal detachments after glaucoma surgeries. A 25-gauge infusion line was placed in the anterior chamber. A 20-gauge (in eyes with hemorrhagic choroidal detachments) or a 25-gauge (in eyes with serous detachments) trocar/cannula system was inserted into the suprachoroidal space 7.0 mm from limbus. After drainage, the cannulas were removed and no sutures were placed. Pars plana vitrectomy was performed only in eyes with concomitant pathology that demanded the additional procedure. The primary outcome measure was presence of choroidal detachment at 1 week, 2 weeks, and 1 month postoperatively. Secondary outcome measures were visual acuity at 6 months and intraocular pressure at 1 week and 1, 3, and 6 months postoperatively. Drainage of hemorrhagic choroidal detachments resulted in resolution of the detachments by 1 month postoperatively. In eyes with serous detachments, resolution was achieved by 1 week postdrainage. In both groups, intraocular pressure increased to at least 10 mmHg by postoperative Week 1. The visual acuity improved in all eyes. No complications related to the transconjunctival technique were noted. Transconjunctival drainage of serous and hemorrhagic choroidal detachments seems to be a feasible and simple surgical option with minimal scleral and conjunctival damage. Pars plana vitrectomy may not be necessary when draining choroidal detachments in this manner.

A comparative immunohistochemical and immunophenotypical study on lymphocytes expression in patients affected by oral lichen planus.

PubMed

Lorenzini, Guido; Viviano, Massimo; Chisci, Elettra; Chisci, Glauco; Picciotti, Maria

2013-09-01

Oral lichen planus (OLP) is an immune-mediated mucocutaneous disease of uncertain aetiology. OLP has many manifestations: reticular, erosive, atrophic, plaque like, papular, bullous, with unique etiopathogenetic working. The purpose of this study is to find a link between different clinical types of lichen and the alterations of lymphocytes on peripheral blood and oral mucosa. A total of 21 patients were enrolled in this study. The mean age of patients was 53.82 years, between 31 and 78 years. OLP Diagnosis was afterwards confirmed by histopathology. Selected patients underwent to clinical evaluation, lesion characterization, incisional biopsy, samples histological analysis, peripheral blood collection. Blood specimens were submitted to cell count determination with differential, characterization of populations and circulating lymphocyte subpopulations using monoclonal antibodies in flow cytometry. Referring to the clinical presentation of lesions, patients were divided in two groups: red lesions (RL) and white lesions (WL) and compared with an age-matched control group. The results of the immunophenotypic study showed correlation between WL and the expression of CD19 lymphocytes (r = 0.693, P = 0.0005). The results of immunohistochemical study performed on histological specimens showed a significant correlation between RL group and expression of all lymphocyte tested (CD3 r = 0.722 P = 0.0002, CD4 r = 0.579 P = 0.0060, CD56 r = 0.513 P = 0.0173, CD8 r = 0.548 P = 0.0102). We assume there is the responsibility of the expression of lymphocytes, not only type but also as quantity, in determining RL or WL manifestation of OLP. Circulating lymphocytes may have a role, too. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oxygen therapy for corneal edema after cataract surgery.

PubMed

Sharifipour, Farideh; Panahi-Bazaz, Mahmoodreza; Idani, Esmaeil; Hajizadeh, Maryam; Saki, Azadeh

2015-07-01

To evaluate the effects of oxygen therapy on corneal edema after cataract surgery. Imam Khomeini Hospital, Ahvaz, Iran. Randomized controlled trial. Patients with severe corneal edema were randomized into 3 groups. Group 1 (control) received conventional therapy including topical sodium chloride, timolol, and betamethasone. Group 2 received the same therapy in addition to systemic normobaric oxygen at a flow rate of 10 L/min for 1 hour twice daily for 3 weeks. Group 3 received conventional therapy and transcorneal oxygen at a flow rate of 5 L/min for 1 hour twice daily for 3 weeks. Preoperative pachymetry and specular microscopy were performed. Pachymetry was performed 1, 3, 5, 7, 10, and 14 days postoperatively. At 1, 3 and 12 months, pachymetry and specular microscopy were performed. The study enrolled 45 patients. Preoperatively, there was no significant difference between the groups. Pachymetry was more than 1000 μm 1 day postoperatively in all patients. The preoperative pachymetry was restored in 14 days in Group 3 only. After 1 year, the endothelial cell count (ECC) was 1603 cells/mm(2), 1693 cells/mm(2), and 1911 cells/mm(2) with a loss of 37%, 32%, and 25% in Group 1, Group 2, and Group 3, respectively (P = .034, Groups 1 and 3). Group 3 had a higher ECC than the control group at 3 months (P = .037) and 1 year (P = .025). One patient in Group 1 and 1 patient in Group 2 developed bullous keratopathy. Transcorneal oxygen decreased corneal edema more rapidly than conventional and systemic oxygen therapies and preserved more endothelial cells than conventional therapy. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Standardised antibacterial Manuka honey in the management of persistent post-operative corneal oedema: a case series.

PubMed

Albietz, Julie M; Lenton, Lee M

2015-09-01

Corneal oedema is a common post-operative problem that delays or prevents visual recovery from ocular surgery. Honey is a supersaturated solution of sugars with an acidic pH, high osmolarity and low water content. These characteristics inhibit the growth of micro-organisms, reduce oedema and promote epithelialisation. This clinical case series describes the use of a regulatory approved Leptospermum species honey ophthalmic product, in the management of post-operative corneal oedema and bullous keratopathy. A retrospective review of 18 consecutive cases (30 eyes) with corneal oedema persisting beyond one month after single or multiple ocular surgical procedures (phacoemulsification cataract surgery and additional procedures) treated with Optimel Antibacterial Manuka Eye Drops twice to three times daily as an adjunctive therapy to conventional topical management with corticosteroid, aqueous suppressants, hypertonic sodium chloride five per cent, eyelid hygiene and artificial tears. Visual acuity and central corneal thickness were measured before and at the conclusion of Optimel treatment. A temporary reduction in corneal epithelial oedema lasting up to several hours was observed after the initial Optimel instillation and was associated with a reduction in central corneal thickness, resolution of epithelial microcysts, collapse of epithelial bullae, improved corneal clarity, improved visualisation of the intraocular structures and improved visual acuity. Additionally, with chronic use, reduction in punctate epitheliopathy, reduction in central corneal thickness and improvement in visual acuity were achieved. Temporary stinging after Optimel instillation was experienced. No adverse infectious or inflammatory events occurred during treatment with Optimel. Optimel was a safe and effective adjunctive therapeutic strategy in the management of persistent post-operative corneal oedema and warrants further investigation in clinical trials. © 2015 The Authors. Clinical and Experimental Optometry © 2015 Optometry Australia.

[Anesthesia for thoracoscopic laser ablation of bullae in a patient with severe bullous emphysema].

PubMed

Saito, Y; Hayashida, M; Arita, H; Hanaoka, K

1995-05-01

A 46-year-old male underwent laser-ablation of emphysematous bullae of the right lung via thoracoscope. For almost a year he had been bedridden because of severe dyspnea on exertion, in spite of medication and oxygen therapy. He also complained of orthopnea at rest and had suffered from body weight loss of 10 kg during the preceding year. Radiologic examination revealed emphysemotous lung with bilateral giant bullae. In spirogram, forced vital capacity in 1 second was markedly low (0.45 l, corresponding to 19% in %FVC1.0), vital capacity moderately depressed (2.41 l, 64%) and residual volume markedly elevated (5.85 l, 387%). Anesthesia was induced and maintained using the combination of thoracic-epidural anesthesia and intravenous anesthesia (midazolam and fentanyl). One lung ventilation (OLV) was used to facilitate thoracoscopic procedure. Mechanical ventilation was conducted at first with an anesthesia ventilator. As the duration of OLV was prolonged, however, the peak airway pressure increased, the tidal volume decreased and the value of percutaneous arterial hemoglobin saturation (SpO2) declined. In order to keep adequate oxygenation, brief periods of two lung ventilation (TLV) became necessary, in addition to the application of continuous positive airway pressure to the non-dependent lung. When ventilation was changed from volume-cycled ventilation to pressure-cycled and from using an anesthesia ventilator to a critical care type ventilator (Servo 900C), sufficient tidal volume was achieved with lower peak airway pressure, producing reasonable Spo2 value with much less frequent TLV. At the end of the surgery bronchopleural fistulae still persisted, with resultant air leak of about 50% of inspired tidal volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Retinal detachment in horses: 40 cases (1998-2005).

PubMed

Strobel, Brian W; Wilkie, David A; Gilger, Brian C

2007-01-01

To determine clinical features, ophthalmic examination findings, etiology, treatment, and outcome of horses diagnosed with retinal detachment (RD). Forty horses, presented to the North Carolina State University and The Ohio State University Veterinary Teaching Hospitals from 1998 to 2005 that were diagnosed with RD. PROCEDURE(S): Horses with documented RD, confirmed either on ophthalmic examination or by ultrasonography, and with a complete medical record were included. Information retrieved from the medical records included signalment, presenting complaint, duration of clinical signs, ophthalmologic examination findings, diagnostics performed, identified cause of the retinal detachment, treatment given, and outcome. Forty horses (46 eyes) were diagnosed with RD. Mean +/- SD duration of clinical signs of ocular disease was 10.5 +/- 14.7 months. Thirty-four horses presented with unilateral involvement, 6 with bilateral, 14 with partial and 32 with complete RD. Ultrasonography was used to make the diagnosis in 26 eyes, while RD was diagnosed on routine ocular examination in 20 eyes. Bullous RD was the only type of RD observed, although small vitreal traction bands were considered secondary to the underlying inflammation or trauma. RD caused by equine recurrent uveitis (ERU) was diagnosed in 27 of 40 (67.5%) horses. Trauma-induced RD involved 10 of the 40 horses (25%). Presenting problems included known ERU (n = 16), acute or progressive vision loss (n = 9), known ocular trauma (n = 6), cataract (n = 6), and a cloudy cornea (n = 3). No horses regained vision after RD despite therapy. Many eyes were enucleated or eviscerated, or the horses were euthanized. Seven eyes with complete RD were noted to be unchanged and comfortable with medical therapy. The visual prognosis of RD in horses is grave; however, horses with nontraumatic RD (most commonly ERU) may be able to maintain a comfortable but blind globe with anti-inflammatory medical therapy.

Descemet’s stripping and non-Descemet’s stripping automated endothelial keratoplasty for microcornea using 6.0 mm donor grafts

PubMed Central

Yokogawa, Hideaki; Kobayashi, Akira; Yamazaki, Natsuko; Ueta, Yoshiki; Hashimoto, Yoshihiro; Tachi, Naoko; Sugiyama, Kazuhisa

2013-01-01

Background The purpose of this paper is to report our experience of Descemet’s stripping and non-Descemet’s stripping automated endothelial keratoplasty (DSAEK/nDSAEK) for microcorneas using 6.0 mm donor grafts. Methods Three eyes of two patients (a 56-year-old woman and a 59-year-old woman) with microcornea and suffering from bullous keratopathy were treated with either DSAEK or nDSAEK. A small donor graft (6.0 mm) was inserted into the anterior chamber using a double glide (Busin glide and intraocular lens sheet glide) donor insertion technique. Both patients were followed for at least 12 months. Clinical outcomes, including intraoperative and postoperative complications, visual acuity, and endothelial cell density were evaluated. Results In all three cases (100%), no intraoperative complications were noted. In one case with a flat keratometry value (32.13 D), a partial donor detachment was noted one day postoperatively, but it was reattached by rebubbling. In another case, rejection was noted 8 months postoperatively, but treatment with systemic corticosteroids was successful. A clear cornea remained in all three cases (100%), with best-corrected visual acuity greater than 20/100 (mean 20/50) at 12 months. Mean postoperative endothelial cell counts were 2,603 ± 18 cells/mm2 at 6 months (7.4% decrease from preoperative donor cell counts) and 1,799 ± 556 cells/mm2 at 12 months (36.5% decrease). Conclusion We report for the first time the successful use of a small donor graft (6.0 mm) for DSAEK/nDSAEK in cases of microcornea. Additional stud ies using a large number of patients are required to evaluate fully the potential advantages and drawbacks of small diameter donor grafts for microcornea. PMID:24109176

The New Zealand National Eye Bank: survival and visual outcome 1 year after penetrating keratoplasty.

PubMed

Patel, Hussain Y; Ormonde, Sue; Brookes, Nigel H; Moffatt, S Louise; Sherwin, Trevor; Pendergrast, David G C; McGhee, Charles N J

2011-07-01

To identify potential donor, recipient, surgical, and postoperative factors that may influence survival and visual outcome of penetrating keratoplasty (PKP). As part of a prospective longitudinal study, the electronic records of the New Zealand National Eye Bank were analyzed for the 10-year period from 1994-2003. Both univariate and multivariate analysis was performed. During the study period, the New Zealand National Eye Bank supplied 1820 corneas for PKP and 1629 (90%) had 1-year follow-up data. Overall, the 1-year survival rate was 87% (n = 1429). Donor factors including age, donor source, cause of death, death-to-preservation interval, endothelial cell density, donor lens status, and storage duration, were not significantly associated with decreased survival. The leading cause of PKP failure was irreversible rejection (7%, n = 114). Independent risk factors identified for decreased PKP survival were: 1 or more episodes of reversible rejection, active inflammation at PKP, preexisting corneal vascularization, intraoperative complications, small graft size (≤ 7.25 mm), large graft size (≥ 8.5 mm), preoperative glaucoma, and a preoperative diagnosis of regraft or trauma. A best-corrected Snellen visual acuity of 6/12 or better was achieved in 60% of eyes [mean: 6/15 (logarithm of the minimum angle of resolution 0.40)]. Keratoconus and Fuchs endothelial dystrophy were the diagnoses with best survival and visual outcome, whereas, bullous keratopathy, trauma or noninfective keratitis were associated with poorer visual outcome. Several independent risk factors were identified that significantly influenced PKP first year survival outcome. This information is valuable to patients and surgeons with respect to determining prognosis and clinical decision making.

Causes of corneal graft failure in India.

PubMed

Dandona, L; Naduvilath, T J; Janarthanan, M; Rao, G N

1998-09-01

The success of corneal grafting in visual rehabilitation of the corneal blind in India depends on survival of the grafts. Understanding the causes of graft failure may help reduce the risk of failure. We studied these causes in a series of 638 graft failures at our institution. Multivariate logistic regression analysis was used to evaluate the association of particular causes of graft failure with indications for grafting, socioeconomic status, age, sex, host corneal vascularization, donor corneal quality, and experience of surgeon. The major causes of graft failure were allograft rejection (29.2%), increased intraocular pressure (16.9%), infection excluding endophthalmitis (15.4%), and surface problems (12.7%). The odds of infection causing graft failure were significantly higher in patients of lower socioeconomic status (odds ratio 2.45, 95% CI 1.45-4.15). Surface problems as a cause of graft failure was significantly associated with grafts done for corneal scarring or for regrafts (odds ratio 3.36, 95% CI 1.80-6.30). Increased intraocular pressure as a cause of graft failure had significant association with grafts done for aphakic or pseudophakic bullous keratopathy, congenital conditions or glaucoma, or regrafts (odds ratio 2.19, 95% CI 1.25-3.84). Corneal dystrophy was the indication for grafting in 12 of the 13 cases of graft failure due to recurrence of host disease. Surface problems, increased intraocular pressure, and infection are modifiable risk factors that are more likely to cause graft failure in certain categories of patients in India. Knowledge about these associations can be helpful in looking for and aggressively treating these modifiable risk factors in the at-risk categories of corneal graft patients. This can possibly reduce the chance of graft failure.

Diffuse cutaneous mastocytosis: analysis of 10 cases and a brief review of the literature.

PubMed

Lange, M; Niedoszytko, M; Nedoszytko, B; Łata, J; Trzeciak, M; Biernat, W

2012-12-01

Diffuse cutaneous mastocytosis (DCM) is an extremely rare disease characterized by mast cell (MCs) infiltration of the entire skin. Little is known about the natural course of DCM. We decided to characterize clinical manifestations, the frequency of MCs mediator-related symptoms and anaphylaxis, risk of systemic mastocytosis (SM) and prognosis, based on 10 cases of DCM, the largest series published to date. Diffuse cutaneous mastocytosis, DCM was confirmed by histopathological examination of skin samples in all cases. SCORing Mastocytosis (SCORMA) Index was used to assess the intensity of DCM. The analysis of clinical symptoms and laboratory tests, including serum tryptase levels was performed. Bone marrow biopsy was done only in selected cases. Large haemorrhagic bullous variant of DCM (five cases) and infiltrative small vesicular variant (five cases) were identified. The skin symptoms appeared in age-dependent manner; blistering predominated in infancy, whereas grain-leather appearance of the skin and pseudoxanthomatous presentation developed with time. SM was not recognized in any of the patients. Mast cell mediator-related symptoms were present in all cases. Anaphylactic shock occurred in three patients. Follow-up performed in seven cases revealed slight improvement of skin symptoms, reflected by decrease of SCORMA Index in all of them. Serum tryptase levels declined with time in six cases. Diffuse cutaneous mastocytosis, DCM is a heterogeneous, severe, cutaneous disease, associated with mediator-related symptoms and risk of anaphylactic shock. Although our results suggest generally favourable prognosis, the review of the literature indicate that SM may occur. Therefore, more guarded prognosis should be given in DCM patients. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Vitreoretinal Complications and Outcomes in 92 Eyes Undergoing Surgery for Modified Osteo-Odonto-Keratoprosthesis: A 10-Year Review.

PubMed

Rishi, Pukhraj; Rishi, Ekta; Agarwal, Vishvesh; Nair, Sridevi; Iyer, Geetha; Srinivasan, Bhaskar; Agarwal, Shweta

2018-06-01

To analyze vitreoretinal (VR) complications and treatment outcomes in eyes undergoing modified osteo-odonto-keratoprosthesis (OOKP) surgery. Retrospective case series. All patients who underwent modified OOKP (mOOKP) surgery at a tertiary eye-care center from March 2003 to February 2013 were included. Medical records were reviewed for relevant medical history, best-corrected visual acuity (BCVA), slit-lamp examination, ultrasound scan, oral examination findings, and VR complications. The BCVA at the last visit. Optimal anatomic outcome was attached retina with a normal intraocular pressure at the last visit. A total of 92 eyes of 90 patients were included. Indications for OOKP included Stevens-Johnson syndrome (n = 53), chemical injury (n = 36), and ocular cicatricial pemphigoid (n = 3). A total of 41 eyes of 39 patients developed VR complications, including vitritis (n = 21), retinal detachment (RD) (n = 12; primary RD = 5), retroprosthetic membrane (RPM) (n = 10; primary RPM = 2), endophthalmitis (n = 8), vitreous hemorrhage (VH) (n = 5; primary VH = 1), serous choroidal detachment (n = 5), hemorrhagic choroidal detachment (n = 2), and leak-related hypotony (n = 1). Mean interval from mOOKP surgery to occurrence of VR complication(s) was 43.8 months (median, 41.9 months; range, 0.2-95.5 months). After treatment of VR complication, visual improvement was seen in 17 eyes (42%) (mean improvement = 1.2 logarithm of the minimum angle of resolution [logMAR]; median, 0.8 logMAR; range, 0.1-2.5 logMAR), visual decline in 7 eyes (14%) (mean decline in BCVA = 0.6 logMAR; median, 0.4 logMAR; range, 0.3-1.8 logMAR), and no change in BCVA in 17 eyes (42%). However, BCVA ≥6/60 was retained in 19 eyes and ≥6/18 was retained in 9 eyes after final VR treatment. Vitreoretinal complications constitute a significant cause of visual morbidity in eyes undergoing mOOKP surgery and pose a challenging situation to manage. However, appropriate and timely intervention can achieve encouraging results. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

An in vitro evaluation of various biomaterials for the development of a tissue-engineered lacrimal gland

NASA Astrophysics Data System (ADS)

Selvam, Shivaram

The most common cause of ocular morbidity in developed countries is dry eye, many cases of which are due to lacrimal insufficiency. It has been established that lacrimal insufficiency results from processes caused by both immune-related and non-immune related events such as Sjogren's syndrome, Stevens-Johnson syndrome, chemical and thermal injuries and ocular cicatricial pemphigoid. Patients with these conditions would benefit from repair of their damaged lacrimal tissue by the creation of a replacement for the lacrimal gland. The new field of tissue engineering built on the interface between principles and methods of the life sciences with those of engineering to develop biocompatible materials has created the possibility for repairing or replacing damaged tissues. This thesis explores the use of tissue engineering principles for the development of a tissue-engineered lacrimal gland. This thesis also contributes to the development of a novel model for addressing lacrimal gland physiology and epithelial fluid transport. The first part of the research work focused on the evaluation of morphological and physiological properties of purified lacrimal gland acinar cells (pLGACs) cultured on various biopolymers: silicone, collagen I, poly-D,L-lactide-co-glycolide (PLGA; 85:15 and 50:50), and poly-L-lactic acid (PLLA) in the presence and absence of an extracellular matrix, MatrigelRTM. Results indicated that PLLA demonstrated the best support expression of acinar cell-like morphology. The second part demonstrated the ex vivo reconstitution of an electrophysiologically functional lacrimal gland tissue on porous polyester membrane scaffolds. Results showed that pLGACs were capable of establishing continuous epithelial monolayers that generate active ionic fluxes consistent with current models for Na +-dependent Cl-- secretion. The third part outlined the fabrication of porous PLLA membranes, the optimal biomaterial for culturing lacrimal epithelial cells. Microporous PLLA-Polyethylene glycol (PEG) blend membranes (mpPLLAbm) with interconnected pores were prepared by the water extraction of PEG from solution cast blend membranes using the solvent-cast/particulate leaching technique. Diffusion experiments on mpPLLAbm (57.1/42.9 wt%) were performed to demonstrate that the membrane was permeable to glucose, L-tryptophan, and dextran.

Methotrexate for ocular inflammatory diseases.

PubMed

Gangaputra, Sapna; Newcomb, Craig W; Liesegang, Teresa L; Kaçmaz, R Oktay; Jabs, Douglas A; Levy-Clarke, Grace A; Nussenblatt, Robert B; Rosenbaum, James T; Suhler, Eric B; Thorne, Jennifer E; Foster, C Stephen; Kempen, John H

2009-11-01

To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation. Retrospective cohort study. Patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to add methotrexate as a single, noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007, inclusive. Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage, route of administration of methotrexate, and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. Control of inflammation, corticosteroid-sparing effects, and incidence of and reason for discontinuation of therapy. Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for >or=28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone

Changing Practice Patterns and Long-term Outcomes of Endothelial Versus Penetrating Keratoplasty: A Prospective Dutch Registry Study.

PubMed

Dickman, Mor M; Peeters, Jean Marie P W U; van den Biggelaar, Frank J H M; Ambergen, Ton A W; van Dongen, Martin C J M; Kruit, Pieter Jan; Nuijts, Rudy M M A

2016-10-01

To compare graft survival, best-corrected visual acuity (BCVA), endothelial cell density (ECD), and refraction following penetrating keratoplasty (PK) vs endothelial keratoplasty (EK) for Fuchs endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK). Nonrandomized treatment comparison with national registry data. All consecutive patients undergoing first keratoplasty for FED and PBK between 1998 and 2014 were analyzed, with a maximum follow-up of 5 years (mean ± SD follow-up 39 ± 20 months, range 0-60 months). Graft survival was analyzed using Kaplan-Meier survival curves and Cox regression analysis. BCVA, ECD, and refractive error were compared using linear mixed models. Main outcome measures were graft survival, BCVA, refraction, and ECD. A total of 5115 keratoplasties (PK = 2390; EK = 2725) were identified. Two-year graft survival following EK was lower compared with PK (94.5% vs 96.3%, HR = 1.56, P = .001). Five-year survival was comparable for EK and PK (93.4% vs 89.7%, HR = 0.89, P = .261). EK graft survival improved significantly over time while remaining stable for PK. One-year BCVA was better following EK vs PK (0.34 vs 0.47 logMAR, P < .001). Astigmatism was lower 1 year after EK vs PK (-1.69 vs -3.52 D, P < .001). One-year ECD was lower after EK vs PK (1472 vs 1859 cells/mm 2 , P < .001). At 3 years, ECD did not differ between EK and PK. Long-term graft survival after EK and PK is high and comparable despite lower short-term survival for EK. EK graft survival improved over time, suggesting a learning curve. EK results in better BCVA, lower astigmatism, and similar long-term ECD compared with PK for FED and PBK. Copyright © 2016 Elsevier Inc. All rights reserved.

Mucocutaneous Manifestations in Patients with Chronic Kidney Disease: A Cross-sectional Study.

PubMed

Rashpa, Rattan S; Mahajan, Vikram K; Kumar, Pankaj; Mehta, Karaninder S; Chauhan, Pushpinder S; Rawat, Ritu; Sharma, Vikas

2018-01-01

Chronic kidney disease (CKD)-associated mucocutaneous manifestations significantly impair the quality of life but often remain understudied. They may also vary across regions, socioeconomic and nutritional status, and racial differences. To study the patterns of mucocutaneous disorders and their prevalence in CKD patients irrespective of clinical stage or dialysis status. 122 (M:F = 77:45) patients aged 21‒85 (Mean ± SD = 57.5 ± 14.0) years having CKD for 3 month to 5 years were studied for mucocutaneous manifestations. Fifty (41%) patients were on hemodialysis for 1‒42 months. Detailed medical history, clinical and mucocutaneous examination, and lab investigations were performed. KOH mounts, skin biopsy, Gram's and Giemsa staining, bacterial or fungal cultures were performed as required. Xerosis in 93 (76.2%), skin pallor in 61 (50%), pruritus in 57 (46.7%), pigmentation in 47 (38.5%), and purpura in 18 (14.8%) patients were the major dermatoses. Bullous lesions and perforating folliculitis occurred in 3 (2.5%) patients each. Major nail abnormalities were pallor (in 35.2%), absent lunula (in 23.8%), nail discoloration (in 18%), and "half-and-half nails" in 16.4% patients, respectively. Hair abnormalities included sparse scalp and body hairs (in 35.2% and 13.1%, respectively) and lusterless hair in 12.3% patients. Coated tongue (in 14.8%), xerostomia (in 12.3%), and macroglossia with teeth indention (in 7.4%) patients were the mucosal manifestations. Xerosis, pruritus, skin pallor/pigmentary changes, nail pallor, absent lunula, nail discoloration, sparse hairs, coated tongue, xerostomia, macroglossia, and infections were the most common mucocutaneous manifestations in the studied patients irrespective of hemodialysis status. Cold and dry climates might be additional aggravators for xerosis/pruritus. Lifelong follow-up may be needed to reduce the morbidity associated with CKD/hemodialysis specific dermatoses appearing over a period.

Free radical development in phacoemulsification cataract surgery.

PubMed

Takahashi, Hiroshi

2005-02-01

Phacoemulsification and aspiration (PEA) has become the most popular cataract surgery, due to the establishment of safe surgical techniques and development of associated instruments. However, corneal endothelial damage still represents a serious complication, as excessive damage can lead to irreversible bullous keratopathy. In addition to causes such as mechanical or heat injuries, free radical formation due to ultrasound has been posited as another cause of corneal endothelium damage in PEA. Ultrasound in aqueous solution induces cavitation, directly causing water molecule disintegration and resulting in the formation of hydroxylradicals, the most potent of the reactive oxygen species. Considering the oxidative insult to endothelial cells caused by free radicals, their presence in the anterior chamber may represent one of the most harmful factors during these procedures. Indeed, some researchers have recently started to evaluate PEA from the perspective of oxidative stress. Conversely, the major ingredient in ophthalmic viscosurgical devices (OVDs), which are indispensable for maintaining the anterior chamber in PEA surgery, is sodium hyaluronate, a known free radical scavenger. OVDs can thus be expected to provide some anti-free radical effect during PEA procedures. In addition, since commercially available OVDs display different properties regarding retention in the anterior chamber during PEA, the anti-free radical effect of OVDs is likely to depend on behavior during irrigation and aspiration. The present study followed standard PEA procedures in an eye model and measured hydroxylradicals in the anterior chamber using electron spin resonance. The kinetics of free radical intensity and effects of several OVDs during clinical PEA were also demonstrated. These studies may be of significance in re-evaluating OVDs as a chemical protectant for corneal endothelium, since the OVD has thus far only been regarded as a physical barrier. In addition, many reports about corneal endothelium damage during PEA have been published, but objective evaluation of various damaging factors has been difficult. The present assay of free radicals in a simulation of clinical PEA offers the first method to quantitatively assess stress on the corneal endothelium.

Fatal toxic epidermal necrolysis associated with minoxidil.

PubMed

Karaoui, Lamis R; Chahine-Chakhtoura, Corinne

2009-04-01

Minoxidil is a direct-acting peripheral vasodilator for the treatment of symptomatic hypertension, or refractory hypertension associated with target organ damage, that is not manageable with a diuretic and two other antihypertensive drugs. The most frequent adverse events associated with minoxidil include hypertrichosis and cardiovascular events related to its powerful antihypertensive effect, and less frequently, rashes, bullous eruptions, and Stevens-Johnson syndrome (SJS). Evidence suggests that SJS and toxic epidermal necrolysis (TEN) are variants of a single disease with common causes and mechanisms, but differing severities. Epidermal detachment is mild in SJS, moderate in overlap SJS-TEN, and severe (> 30% of body surface area) in TEN. We describe a case of minoxidil-associated SJS that evolved into fatal TEN. A 69-year-old African-American woman with a history of chronic kidney disease was admitted to the hospital for a cerebrovascular accident and uncontrolled hypertension. On hospital day 12, oral minoxidil was added to her drug regimen. On day 23, she developed a maculopapular rash on her face that gradually diffused to her chest and back. Vesicles and papular lesions extended to her extremities and mucosal membranes; results of a skin biopsy revealed SJS. A positive Nikolsky's sign (blisters spread on application of pressure) was detected. On days 27-31, diffuse bullae developed with rash exacerbation. Skin detachment exceeded 30% and was consistent with TEN. The patient died on day 39. An evaluation of the causality and time course suggested that minoxidil was the most likely culpable drug, with a Naranjo adverse drug reaction probability scale score indicating that the likelihood of the association was possible (score of 3). The mechanism of this reaction has not been well elucidated. It may be related to an impaired clearance of the minoxidil metabolite, or an immune stimulation resulting in apoptosis and epidermis destruction. To our knowledge, this is the first case report of fatal TEN associated with minoxidil. This case report emphasizes the importance of monitoring for serious dermatologic reactions in patients receiving minoxidil therapy.

CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

PubMed

Morel, Esther; Escamochero, Salvador; Cabañas, Rosario; Díaz, Rosa; Fiandor, Ana; Bellón, Teresa

2010-03-01

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe, bullous cutaneous diseases with uncertain pathogenesis, although cytotoxic T cells seem to be involved. Natural killer (NK)-like activity has been found in blister infiltrates. Cytotoxic T lymphocytes (CTLs) with NK-like activity (NK-CTLs) have been shown to express T-cell receptors restricted by the HLA-Ib molecule HLA-E. Alternatively, the HLA-E-specific activating receptor CD94/NKG2C can trigger T-cell receptor-independent cytotoxicity in CTLs. Our aim was to test whether HLA-E expression sensitizes keratinocytes to killing by CTLs with NK-like activity and to explore the expression of activating receptors specific for HLA-E in blister cytotoxic lymphocytes. We used flow cytometry and immunohistochemistry to analyze HLA-E expression in keratinocytes from affected skin in patients with SJS, TEN, and other less severe drug-induced exanthemas. The expression of CD94/NKG2C was analyzed by means of flow cytometry in PBMCs and blister cells from patients. PBMCs and blister cells were analyzed for their ability to kill HLA-E-expressing cells. Involvement of CD94/NKG2C in triggering degranulation of cytolytic cells was explored by means of CD107a mobilization assays and standard cytotoxicity chromium release assays. We found that keratinocytes from affected skin expressed HLA-E and that cell-surface HLA-E sensitizes keratinocytes to killing by CD94/NKG2C(+) CTLs. Frequencies of CD94/NKG2C(+) peripheral blood T and NK cells were increased in patients with SJS and TEN during the acute phase. Moreover, activated blister T and NK lymphocytes expressed CD94/NKG2C and were able to degranulate in response to HLA-E(+) cells in an NKG2C-dependent manner. CD94/NKG2C might be involved in triggering cytotoxic lymphocytes in patients with SJS and TEN.

Autoimmune and infectious skin diseases that target desmogleins

PubMed Central

AMAGAI, Masayuki

2010-01-01

Desmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, the desmogleins (Dsg) and desmocollins (Dsc), which are cadherin-type cell–cell adhesion molecules and are anchored to intermediate filaments of keratin through interactions with plakoglobin and desmoplakin. Desmosomes play an important role in maintaining the proper structure and barrier function of the epidermis and mucous epithelia. Four Dsg isoforms have been identified to date, Dsg1–Dsg4, and are involved in several skin and heart diseases. Dsg1 and Dsg3 are the two major Dsg isoforms in the skin and mucous membranes, and are targeted by IgG autoantibodies in pemphigus, an autoimmune disease of the skin and mucous membranes. Dsg1 is also targeted by exfoliative toxin (ET) released by Staphylococcus aureus in the infectious skin diseases bullous impetigo and staphylococcal scalded skin syndrome (SSSS). ET is a unique serine protease that shows lock and key specificity to Dsg1. Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia. Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development. Recently, an active disease model for pemphigus was generated by a unique approach using autoantigen-deficient mice that do not acquire tolerance against the defective autoantigen. Adoptive transfer of Dsg3−/− lymphocytes into mice expressing Dsg3 induces stable anti-Dsg3 IgG production with development of the pemphigus phenotype. This mouse model is a valuable tool with which to investigate immunological mechanisms of harmful IgG autoantibody production in pemphigus. Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic strategies with minimal side effects. PMID:20467217

Pseudocarcinomatous urothelial hyperplasia of the bladder: clinical findings and followup of 70 patients.

PubMed

Kryvenko, Oleksandr N; Epstein, Jonathan I

2013-06-01

Pseudocarcinomatous urothelial hyperplasia is rare and almost exclusively described in the pathology literature. We reviewed 70 cases during a 9.5-year period. Two specimens were taken from biopsies done at our institution and 68 were from cases referred for consultation. Samples were obtained from a total of 60 men and 10 women with a mean age of 67 years (range 33 to 85). Of 68 patients with information available 52 (76.5%) underwent prior pelvic irradiation, 2 received systemic chemotherapy only, 3 had an indwelling bladder catheter, 2 received intravesical chemotherapy, 1 had been treated with radical prostatectomy, 4 had severe peripheral vascular disease, 1 had an arteriovenous malformation, 1 had sickle cell disease and only 2 (2.9%) had no identifiable contributing factors. Pseudocarcinomatous urothelial hyperplasia developed an average of 54.6 months (range 9 months to 13 years) after prior irradiation. Hematuria was the most common clinical presentation, noted in 45 of 51 patients with data available. Of 48 patients with data endoscopy revealed erythema in 20, a papillary/polypoid lesion in 12, broad-based elevated erythematous lesions in 6, erythematous bullous edema in 5, shallow bleeding ulcers in 4 and prominent trabeculation in 1. Additional findings in the bladder were carcinoma in situ in 3 cases, and dysplasia, low grade papillary urothelial carcinoma and papillary urothelial hyperplasia in 1 each. Three of the 40 patients with an average followup of 27 months (range 1 to 94) subsequently had urothelial carcinoma, including 1 who had prior positive cytology and fluorescence in situ hybridization, 1 with prior high grade papillary urothelial carcinoma and 1 with an unknown history. Although pseudocarcinomatous urothelial hyperplasia mimics invasive urothelial carcinoma clinically and histologically, it is not related to urothelial neoplasms. Almost all patients have causes of bladder ischemia, most commonly a history of remote prior pelvic irradiation. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Mucocutaneous Manifestations in Patients with Chronic Kidney Disease: A Cross-sectional Study

PubMed Central

Rashpa, Rattan S.; Mahajan, Vikram K.; Kumar, Pankaj; Mehta, Karaninder S.; Chauhan, Pushpinder S.; Rawat, Ritu; Sharma, Vikas

2018-01-01

Background: Chronic kidney disease (CKD)-associated mucocutaneous manifestations significantly impair the quality of life but often remain understudied. They may also vary across regions, socioeconomic and nutritional status, and racial differences. Objectives: To study the patterns of mucocutaneous disorders and their prevalence in CKD patients irrespective of clinical stage or dialysis status. Materials and Methods: 122 (M:F = 77:45) patients aged 21‒85 (Mean ± SD = 57.5 ± 14.0) years having CKD for 3 month to 5 years were studied for mucocutaneous manifestations. Fifty (41%) patients were on hemodialysis for 1‒42 months. Detailed medical history, clinical and mucocutaneous examination, and lab investigations were performed. KOH mounts, skin biopsy, Gram's and Giemsa staining, bacterial or fungal cultures were performed as required. Results: Xerosis in 93 (76.2%), skin pallor in 61 (50%), pruritus in 57 (46.7%), pigmentation in 47 (38.5%), and purpura in 18 (14.8%) patients were the major dermatoses. Bullous lesions and perforating folliculitis occurred in 3 (2.5%) patients each. Major nail abnormalities were pallor (in 35.2%), absent lunula (in 23.8%), nail discoloration (in 18%), and “half-and-half nails” in 16.4% patients, respectively. Hair abnormalities included sparse scalp and body hairs (in 35.2% and 13.1%, respectively) and lusterless hair in 12.3% patients. Coated tongue (in 14.8%), xerostomia (in 12.3%), and macroglossia with teeth indention (in 7.4%) patients were the mucosal manifestations. Conclusions: Xerosis, pruritus, skin pallor/pigmentary changes, nail pallor, absent lunula, nail discoloration, sparse hairs, coated tongue, xerostomia, macroglossia, and infections were the most common mucocutaneous manifestations in the studied patients irrespective of hemodialysis status. Cold and dry climates might be additional aggravators for xerosis/pruritus. Lifelong follow-up may be needed to reduce the morbidity associated with CKD/hemodialysis specific dermatoses appearing over a period. PMID:29441293

The natural history of Stevens–Johnson syndrome: patterns of chronic ocular disease and the role of systemic immunosuppressive therapy

PubMed Central

De Rojas, M Victoria; Dart, John K G; Saw, Valerie P J

2007-01-01

Objective To characterize patterns of chronic ocular disease in patients with Stevens–Johnson syndrome (SJS) and its variant toxic epidermal necrolysis (TEN), and to describe their response to treatment. Methods Retrospective case series. A review of hospital records of 30 patients (60 eyes) with ocular manifestations of SJS or TEN was carried out. The principal outcome measure was to identify and classify the patterns of chronic ocular disease in SJS and TEN. The secondary outcome measure was the response to treatment. Results Patterns of chronic ocular disease observed after the acute episode included: mild/moderate SJS, severe SJS, ocular surface failure (SJS‐OSF), recurrent episodic inflammation (SJS‐RI), scleritis (SJS‐S) and progressive conjunctival cicatrisation resembling mucous membrane pemphigoid (SJS‐MMP). The median follow‐up was 5 years (range 0–29). 19 patients (29 eyes (48%)) developed SJS‐OSF, SJS‐RI, SJS‐S or SJS‐MMP during follow‐up. SJS‐OSF was present in 12 patients (18 eyes (30%)). In 5 patients (eight eyes) this developed 1 year after the acute illness, without any further inflammatory episodes; it was associated with SJS‐RI in 1 patient (2 eyes), with SJS‐RI and SJS‐S in 1 patient (1 eye), with SJS‐S in 1 patient (1 eye) and with SJS‐MMP in 4 patients (6 eyes). Episodes of SJS‐RI occurred in 4 patients (7 eyes (12%)). The median time from acute disease to the first episode of SJS‐RI was 8.5 years (range 5–63). SJS‐S developed in 2 patients (4 eyes (7%)), of which 2 eyes subsequently developed SJS‐OSF. SJS‐MMP developed in 5 patients (10 eyes (16.6%)). The median duration from the acute stage to the diagnosis of SJS‐MMP was 2 years (range 1–14). Immunosuppressive therapy successfully controlled inflammation in 10/10 patients with SJS‐MMP, SJS‐RI or SJS‐S. Conclusion Ocular disease in SJS/TEN is not limited solely to the sequelae of the acute phase illness. Patients and physicians need to know that ocular disease progression, due to surface failure and/or acute inflammatory conditions, may occur at variable periods following the acute disease episode. Recognition of this, and prompt access to specialist services, may optimise management of these uncommon patterns of disease in SJS. PMID:17314145

Methotrexate for Ocular Inflammatory Diseases

PubMed Central

Gangaputra, Sapna; Newcomb, Craig W.; Liesegang, Teresa L.; COT; CRC; Kaçmaz, R. Oktay; Jabs, Douglas A.; Levy-Clarke, Grace A.; Nussenblatt, Robert B.; Rosenbaum, James T.; Suhler, Eric B.; Thorne, Jennifer E.; Foster, C. Stephen; Kempen, John H.

2013-01-01

Purpose To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation. Design Retrospective cohort study. Participants Patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to add methotrexate as a single, noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007, inclusive. Methods Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage, route of administration of methotrexate, and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. Main Outcome Measures Control of inflammation, corticosteroid-sparing effects, and incidence of and reason for discontinuation of therapy. Results Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for ≥28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone ≤10 mg/d) was achieved within 6 months among 46.1%, 41.3%, 20.7%, 37.3%, 36.5%, and 50.9%, respectively. Overall, success within 12 months was 66% and 58.4% for sustained control and corticosteroid sparing ≤10 mg), respectively. Methotrexate was discontinued within 1 year by 42% of patients. It was discontinued owing to ineffectiveness in 50 patients (13%); 60 patients (16%) discontinued because of side effects, which typically were reversible with dose reduction or discontinuation. Remission was seen in 43 patients, with 7.7% remitting within 1 year of treatment. Conclusions Our data suggest that adding methotrexate to an anti-inflammatory regimen not involving other noncorticosteroid immunosuppressive drugs is moderately effective for management of inflammatory activity and for achieving corticosteroid-sparing objectives, although many months may be required for therapeutic success. Methotrexate was well tolerated by most patients, and seems to convey little risk of serious side effects during treatment. Financial Disclosure(s) The authors have no proprietary or commercial interests in any of the materials discussed in this article. PMID:19748676

Clinical outcomes of Descemet membrane endothelial keratoplasty using eye bank-prepared tissues.

PubMed

Deng, Sophie X; Sanchez, P James; Chen, Luxia

2015-03-01

To investigate the outcomes of Descemet membrane endothelial keratoplasty (DMEK) using prestripped donor tissue prepared by an eye bank. Retrospective, noncomparative case series. This retrospective, noncomparative, observational study investigated the outcomes of the first 40 consecutive DMEK procedures performed by a single surgeon using prestripped tissues prepared by a single eye bank during the period September 17, 2013 to July 1, 2014. A new technique to unfold the Descemet membrane grafts using a single cannula was described. Medical records were reviewed to obtain the prestripped and poststripped endothelial cell counts (ECC), postoperative ECC, visual acuity measurements, and complications. Of the 43 prestripped tissues received, 40 were transplanted. The leading indications for DMEK were Fuchs endothelial corneal dystrophy (n = 28) and bullous keratopathy (n = 11). Nine DMEK procedures were performed in combination with phacoemulsification and posterior chamber intraocular lens implantation. Six patients had undergone prior glaucoma surgeries. The mean follow-up duration was 5.3 months (range, 1 week to 11 months). Preoperative spectacle-corrected visual acuity was ≤20/200 in 8 patients (20%) and ≤20/40 in 37 patients (92.5%). Primary graft failure occurred in the first case. Thirty-eight patients had improved vision postoperatively. Among the 39 patients who had successful DMEK, postoperative BCVA was ≥20/20 in 20 patients (51.2%), ≥20/25 in 30 patients (76.9%), and ≥20/40 in 34 patients (87.2%) by the last follow-up. There was no secondary graft failure. Rejection occurred in 2 patients because of self-discontinuation of topical corticosteroid. The most common complication was partial detachment requiring air injection (11 of 40 patients; 27.5%). Mean ECC loss after stripping of Descemet membrane was 3.9% (range, 6.5% gain to 14.5% loss). During the first 6 months after transplantation, the average ECC loss was 30.5% (range, 3.8%-67.4% loss). DMEK using eye bank-prepared tissue achieved outcomes comparable to those reported for DMEK using surgeon-prepared tissue. Published by Elsevier Inc.

[Characterization of a canine model of dystrophic bullous epidermolysis (DBE). Development of a gene therapy protocol].

PubMed

Magnol, Jean-Pierre; Pin, Didier; Palazzi, Xavier; Lacour, Jean-Philippe; Gache, Yannick; Meneguzzi, Guerrino

2005-01-01

The main human forms of epidermolysis bullosa (EB), namely EB simplex, junctional EB and dystrophic EB, have also been described in domestic animals (small and large ruminants, and horses) and companion animals (cats and dogs). A recent description of dystrophic epidermolysis bullosa (DEB) in Golden Retriever dogs provided details of the principal clinical, morphological and genetic features. The disease is characterized by blisters and erosions in the oral and esophageal epithelia, together with milia, nails dystrophy and growth retardation. The cutaneous lesions regress spontaneously in adult dogs, whereas the epithelial lesions persist, aggravate and spread, notably to the cornea. Classical microscopic studies (light and electron microscopy, indirect immunofluorescence) have revealed anchoring fibril abnormalities and very low-level and heterogenous expression of collagen type VII. The culprit mutation (G1906S) in the canine gene COL7A1 (87.8% nucleotide sequence identity to the human counterpart) involves the replacement of guanine 5716 by adenine, leading to glycine substitution by serine at amino acid position 1906. Transmission in kennels occurs in recessive mode (RDEB). These features recall certain human forms of DEB, and particularly those with a phenotype intermediate between gravis (the so-called Hallopeau-Siemens form) and mitis. No curative treatment of human EB is currently available, and efforts are therefore being made to develop a gene therapy protocol in animals. The first steps have already been successfully achieved, namely the development of a recombinant virus vector able to insert the wild-type gene into the keratinocyte genome, and grafting of artificial skin containing transfected canine keratinocytes in nude mice. The recombinant vectors are Moloney-type retroviruses (MMLV-PCMV), and the Zeocin resistance gene is used to select transduced cells. The artificial skin reconstructed in vitro is of the full-thickness type. Despite the large size of the transduced (9 kb), 95% of cells are transduced and produce large amounts of wild-type collagen. Two key issues remain, however: the possible immunogenicity of the transgene product and the persistence of transgene expression in individuals with a functional immune system. Golden Retriever dogs will provide a suitable animal model for these studies.

Five-Year Graft Survival Comparing Descemet Stripping Automated Endothelial Keratoplasty and Penetrating Keratoplasty.

PubMed

Ang, Marcus; Soh, Yuqiang; Htoon, Hla Myint; Mehta, Jodhbir S; Tan, Donald

2016-08-01

To compare 5-year graft survival after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) in Asian eyes. Prospective, nested, cohort study. Consecutive patients who underwent DSAEK (423 eyes) or PK (405 eyes) for Fuchs' endothelial dystrophy (FED) or bullous keratopathy (BK). Clinical data and donor and recipient characteristics were recorded from our prospective cohort from the Singapore Corneal Transplant Registry. All surgeries were performed by the corneal surgeons at our center, which included cases performed or partially performed by corneal fellows in training under direct supervision. Five-year cumulative graft survival. Overall mean age was 67.8±9.8 years, and 50.1% of patients were men. There were no significant differences in age (P = 0.261) or gender (P = 0.78) between PK and DSAEK groups in our predominantly Chinese (76.6%) Asian cohort, with more BK compared with FED (68.1% vs. 31.9%; P < 0.001). Overall 5-year graft survival was superior for DSAEK compared with PK (79.4% vs. 66.5%; P < 0.001, log-rank test). Median 5-year percent endothelial cell density loss was significantly greater in PK compared with DSAEK (60.9% vs. 48.7%; P = 0.007). Cox regression analysis revealed that BK was a significant factor associated with graft failure (hazard ratio [HR], 3.30; 95% confidence interval [CI], 2.05-5.33; P < 0.001), and PK was more likely to fail compared with endothelial keratoplasty (HR, 1.61; 95% CI, 1.08-2.41; P = 0.02) adjusting for confounders such as recipient age, gender, and donor factors. Five-year cumulative incidence of complications such as graft rejection (P < 0.001), epitheliopathy (P < 0.001), suture-related corneal infections (P < 0.001), and wound dehiscence (P = 0.002) were greater in the PK group compared with the DSAEK group. In Asian eyes from the same study cohort with standardized surgical and postoperative regimes, 5-year graft survival was superior for DSAEK compared with PK in eyes with FED and BK. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Amniotic membrane transplantation for ocular disease: a review of the first 233 cases from the UK user group

PubMed Central

Saw, Valerie P J; Minassian, Darwin; Dart, John K G; Ramsay, Andrew; Henderson, Hugo; Poniatowski, Stefan; Warwick, Ruth M; Cabral, Suzanne

2007-01-01

Background Amniotic membrane transplantation (AMT), as a new tool in the armamentarium of therapies available for ocular surface problems, became widely available in the UK in 1998. This study evaluates the indications for treatment, the surgical procedures used, and the results of a subset of the first AMT cases carried out by the group using this nationally available supply. This user group model provides data which is different from that obtained from uncontrolled case series, or clinical trials, and may be more representative of the outcomes that can be expected when a procedure becomes widely available. Methods The first 233 AMTs, performed by the UK user group, were evaluated by audit and outcomes were assessed at 3 months. Results Of the 233 transplants, there were 126 (54.1%) valid outcome returns: the outcome for persistent epithelial defects was a healed and stable surface in 11/35 (31.4%, 95% CI 16.9 to 49.3); for chemical/thermal injuries, a healed uninflamed eye with clear cornea in 5/18 (27.8%, 95% CI 9.7 to 53.4); for bullous keratopathy a pain‐free, stable surface without bullae in 4/18 (22.2%, 95% CI 6.4 to 47.6); for ocular surface reconstruction, an epithelialised uninflamed conjunctiva without scarring in 12/23 (52.2%, 95% CI 30.6 to 73.2); and for limbal stem cell deficiency, a corneal phenotype in 4/7 (57.1%). The operative technique least associated with failure was use of a bandage contact lens at the end of the procedure (OR 0.19, 95% CI 0.06 to 0.59, p = 0.004). Previous treatment with topical steroids was significantly associated with failure (OR 5.70, 95% CI 1.77 to 18.43, p = 0.004). Conclusion Although the outcome criteria used in this study were stringent, and the follow‐up duration was short, the results of AMT by this user group were generally less favourable than those of previously reported case series. Controlled clinical trials would improve the quality of evidence for use of amniotic membrane in ocular disease. PMID:17314154

Scleral Buckling under a Slit-lamp Illumination System with a Contact Wide-angle Viewing Lens Compared with an Indirect Ophthalmoscope.

PubMed

Choi, Seung Yong; Lee, Youlim; Kim, Mirinae; Park, Young Hoon

2018-04-01

To investigate the outcomes of scleral buckling surgery performed under a slit-lamp illumination system (Visulux) with a contact wide-angle viewing lens (Mini Quad) in patients with rhegmatogenous retinal detachment (RRD) and to compare these outcomes with those of surgery performed under an indirect ophthalmoscope. By retrospective review of electronic medical records, patients with RRD who had undergone scleral buckling surgery were identified. Scleral buckling surgeries were performed with two illumination instruments, a slit-lamp (SL group) and an indirect ophthalmoscope (IO group). Subretinal fluid drainage, cryopexy, and intravitreal gas injection were performed optionally. At 6 months after surgery, anatomical and functional outcomes were evaluated and compared between the two groups. Operation time was also compared between the two groups. Of the 45 total patients (45 eyes), 28 were included in the SL group, and 17 were included in the IO group. In the SL and IO groups, the primary anatomical success rate was 89.3% and 88.2%, respectively (p = 0.92). The logarithm of the minimal angle of resolution change, which reflects improvement in best-corrected visual acuity after surgery, was -0.19 ± 0.38 in the SL group and -0.21 ± 0.63 in the IO group; this difference was not statistically significant (p = 0.91). The mean operation time was significantly shorter in the SL group (78.9 ± 11.8 minutes) than in the IO group (100.0 ± 13.9 minutes, p < 0.001), especially for patients who underwent additional procedures such as subretinal fluid drainage and cryopexy (81.4 ± 12.9 and 103.5 ± 12.3 minutes, respectively, p < 0.001). Scleral buckling surgery performed under a slit-lamp illumination system yielded a similar anatomical success rate and similar functional improvement in RRD compared with surgery performed under an indirect ophthalmoscope. The slit-lamp system could save time, especially in bullous RRD, which requires additional subretinal fluid drainage. © 2018 The Korean Ophthalmological Society.

Effect of N-acetylcysteine combined with infliximab on toxic epidermal necrolysis. A proof-of-concept study.

PubMed

Paquet, Philippe; Jennes, Serge; Rousseau, Anne Françoise; Libon, Florence; Delvenne, Philippe; Piérard, Gérald E

2014-12-01

The pathophysiology of toxic epidermal necrolysis (TEN) is thought to be related to a drug-induced oxidative stress combined with TNFα overexpression by keratinocytes. None of the current treatments for TEN including systemic corticosteroids, cyclosporine and intravenous administration of immunoglobulins has proven superior over supportive care only. A total of 10 TEN patients were enrolled to be treated at admission in burn units with the antioxidant N-acetylcysteine [NAC, 150mg/kg in a 20-h intravenous (IV) administration], or the combination of the same IV NAC perfusion with the anti-TNFα antibody infliximab (Remicade(®)), administered at a 5mg/kg dosage as a single 2-h IV administration. TEN was confirmed by a skin biopsy taken from a bullous lesion. At entry in the trial and 48h later, the illness auxiliary score (IAS) of clinical severity was determined and the extent in altered skin area (erythema and blisters) was assessed as a relative body area. Skin biopsies of both clinically uninvolved and erythematous areas were collected and immunohistochemistry was performed for assessing the density of inflammatory cells (CD8+ T cells, CD68+ macrophages) and keratinocytes enriched in intracellular calcium (Ca(++)) identified by the Mac387 anti-calprotectin antibody. No unexpected drug-induced adverse event was noticed. After 48h of both treatment modalities, improvements were not observed in the extent of skin involvement and in IAS. Immunohistopathology showed the absence of reduction in the amount of intraepidermal inflammatory cells. An increased intracellular Ca(++) load in clinically uninvolved keratinocytes and in erythematous epidermis was noticed. This latter finding suggested the progression in the way of the apoptotic process. On burn unit discharge, the survival in each modality of treatment was not improved compared to the expected outcomes determined from the IAS at admission. In this proof-to-concept attempt, NAC treatment or its combination with infliximab did not appear to reverse the evolving TEN process. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Diverse cutaneous adverse eruptions caused by anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies: clinical features and management.

PubMed

Shen, John; Chang, Jason; Mendenhall, Melody; Cherry, Grace; Goldman, Jonathan W; Kulkarni, Rajan P

2018-01-01

The anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies have shown exceptional activity in many cancers. However, these immunotherapies can also result in diverse adverse cutaneous eruptions that need to be better characterized for ongoing management. The objective was to provide clinical and histopathologic descriptions of the variety of cutaneous adverse events seen in patients who received anti-PD-1/PD-L1 treatment and discuss their management. Patients with advanced cancers in clinical trials at University of California Los Angeles (UCLA), receiving anti-PD-1/PD-L1 treatment between 2012 and 2016 who developed cutaneous eruptions and were evaluated in the dermatology clinic were included in this retrospective case series study. A total of 16 patients were included in this study; of these, five were treated with pembrolizumab alone, two with avelumab alone, eight with nivolumab plus ipilimumab and one with nivolumab plus T-Vec. Of these 16 patients, eight had received systemic chemotherapy, six had received radiotherapy, and one had received trememlimumab prior to the immunotherapies described in this study. Cutaneous eruptions occurred at variable times, from week 1 to 88, with a median of 11.5 weeks; the morphologies included lichenoid, bullous, psoriasiform, macular, morbiliform appearances, and alopecia which were confirmed histopathologically in several of the cases. All cutaneous immune-related adverse events were either grade 1 or 2. Ten patients were treated with topical corticosteroids, and one also received NBUVB. Four patients eventually required systemic steroids. Three required discontinuation of their anti-PD-1/PD-L1 therapy secondary to the cutaneous eruptions. There are several different types of adverse cutaneous morphologies that may be seen with administration of PD-1 and PD-L1 inhibitors. Identifying the patterns of eruption may assist in prompt treatment. Most eruptions could be managed with topical corticosteroids and without discontinuation of the systemic treatment.

Desmoglein 3-specific T regulatory 1 cells consist of two subpopulations with differential expression of the transcription factor Foxp3

PubMed Central

Veldman, Christian; Pahl, Andreas; Hertl, Michael

2009-01-01

Pemphigus vulgaris (PV) is an autoimmune bullous skin disorder associated with autoantibodies against desmoglein (Dsg) 3. An imbalance of type 1 regulatory T (Tr1) cells and T helper type 2 (Th2) cells specific for Dsg3 may be critical for the loss of tolerance against Dsg3 in PV. Within the population of Dsg3-responsive, interleukin (IL)-10-secreting Tr1 cell clones, two major subpopulations were identified and sorted by fluorescence-activated cell sorting (FACS) based on their size and granularity. Upon in vitro culture, the larger subpopulation differentiated back into the two former subpopulations of the Tr1 cell clones, while the smaller subpopulation died within 2 weeks. The smaller subpopulation of the Tr1 cell clones was characterized by the expression of Foxp3, the secretion of IL-10, transforming growth factor (TGF)-β and IL-5 upon stimulation with Dsg3, a proliferative response to IL-2 but not to Dsg3 or mitogenic stimuli, and an inhibitory effect on the proliferative response of Dsg3-responsive Th clones in a Dsg3-specific manner. In contrast, the larger subpopulation showed a Th-like phenotype, lacking Foxp3, cytotoxic T-lymphocyte antigen 4 (CTLA4) and glucocorticoid-induced tumour necrosis factor receptor (GITR) expression and IL-2 secretion, and did not mount a proliferative response to Dsg3 and mitogenic stimuli. The two Tr1 subpopulations showed expression of identical T-cell receptor (TCR) Vβ chains which varied among the PV patients studied. Upon inhibition of Foxp3, the smaller Tr1 subpopulation developed a proliferate response to Dsg3 and mitogenic stimuli, no longer suppressed Dsg3-specific Th cells, lost expression of GITR and CTLA4 and secreted IL-2. Thus, our observations suggest a distinct relationship between Dsg3-specific Tr1 and Th-like cells which may be critical for the continuous generation and survival of Dsg3-specific Tr1 cells. PMID:18800988

New insights into desmosome regulation and pemphigus blistering as a desmosome-remodeling disease.

PubMed

Kitajima, Yasuo

2013-01-01

Desmosomes in keratinocytes are the most important intercellular adhering junctions that provide structural strength for the epidermis. These junctions are connected directly with desmosomal cadherin proteins. Desmosomal cadherins are divided into four desmogleins (Dsgs), Dsg1-4, and three desmocollins (Dscs), Dsc1-3, all of which are involved in desmosomal adhesion by homo- and/or heterophilic binding between Dsgs and Dscs in a Ca(2+)-dependent manner. Cadherins are present on the cell surface and anchor keratin intermediate filaments (KIFs) to their inner cytoplasmic surface to generate an intracellular KIF-skeletal scaffold through several associate proteins, including plakoglobin, plakophillin, and desmoplakins. As such, the desmosomal contacts between adjacent cells generate an intercellular KIF scaffold throughout the whole epidermal sheet. However, despite these critical roles in maintaining epidermal adhesion and integrity, desmosomes are not static structures. Rather, they are dynamic units that undergo regular remodeling, i.e., assembly and disassembly, to allow for cell migration within the epidermis in response to outside-in signaling during epidermal differentiation. Recently, two cell-cell adhesion states controlled by desmosomes have been recognized, including "stable hyperadhesion (Ca(2+)-independent)" and "dynamic weak-adhesion (Ca(2+)-dependent)" conditions. These conditions are mutually reversible through cell signaling events involving protein kinase C (PKC) and epidermal growth factor receptor. Pemphigus vulgaris (PV) is an autoimmune bullous disease caused by anti-Dsg3 antibodies. Binding of these antibodies to Dsg3 causes endocytosis of Dsg3 from the cell surface and results in the specific depletion of Dsg3 from desmosomes, an event linked to acantholysis in the epidermis. This binding of anti-Dsg3 antibody to Dsg3 in epidermal keratinocytes activates PKC, to generate the "weak-adhesion (Ca(2+)-dependent)" state of desmosomes. The weak-adhesion desmosomes appear to be the susceptible desmosomal state and a prerequisite for Dsg3 depletion from desmosomes, pivotal and specific events leading to PV blistering. These observations allow us to propose a concept for pemphigus blistering disorders as a "desmosome-remodeling impairment disease" involving a mechanism of Dsg3 nonassembly and depletion from desmosomes through PV immunoglobulin G-activated intracellular signaling events. Copyright © 2012. Published by Elsevier B.V.

Visual rehabilitation in end-stage inflammatory ocular surface disease with the osteo-odonto-keratoprosthesis: results from the UK.

PubMed

Liu, C; Okera, S; Tandon, R; Herold, J; Hull, C; Thorp, S

2008-09-01

To report the long-term results of osteo-odonto-keratoprosthesis (OOKP) surgery in the visual rehabilitation of patients with corneal blindness from end-stage inflammatory ocular surface disease. A non-comparative retrospective case series of 36 consecutive patients treated at the National OOKP referral centre in Brighton, UK, between November 1996 and March 2006. A total of 36 patients, with age ranging from 19 to 87 years (mean 51 (SD 19) years), were included in the analysis. The main preoperative diagnoses were Stevens-Johnson syndrome (n = 16, or 44%), severe thermal or chemical burns (n = 6, or 17%), and mucous membrane pemphigoid (n = 5, or 14%). The remainder of the cases comprised miscellaneous causes of dry eye (n = 9, or 25%), which included one each of graft versus host disease, ectodermal dysplasia, ionising radiation damage, cicatrising conjunctivitis from topical medication, trachoma, congenital trigeminal nerve hypoplasia, linear IgA disease, Sjögren syndrome and nutritional deficiency. Follow-up ranged from 6 months to 9 years (mean 3.9 (SD 2.5) years). Anatomical retention during the entirety of the follow-up period was seen in 72% of patients. The main factor resulting in anatomical failure was resorption of the OOKP lamina, which occurred in seven cases (or 19%). Predicted resorption in three cases resulted in successful planned exchange of the lamina, but two cases underwent emergency removal of the OOKP, and two cases developed endophthalmitis. Human leucocyte antigen-matched allografts suffered a higher rate of laminar resorption. Out of the entire cohort, 30 patients (or 83%) had some improvement in vision, 28 (or 78%) achieved vision of 6/60 or better, and 19 (or 53%) achieved 6/12 or better. The best-achieved vision was retained throughout the follow-up period in 61% of cases. Survival analysis suggested that the probability of retaining vision >6/60 5 years after surgery was 53 (10)%. Vision-threatening complications occurred in nine cases (or 25%) and included endophthalmitis, retinal detachment and glaucoma. De novo glaucoma occurred in six patients (or 24%) but was seen overall in 17 patients (or 47%), 10 of whom required surgical treatment. OOKP surgery can restore useful and lasting vision in patients suffering from end-stage ocular surface disease, for whom conventional corneal surgery is not possible. The main problems seen in this study were laminar resorption, particularly in allografts, and glaucoma.

Cutaneous manifestations of systemic lupus erythematosus in a tertiary referral center.

PubMed

Kole, Alakes Kumar; Ghosh, Alakendu

2009-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiorgan involvement. The skin is the second most commonly affected organ. SLE with skin lesions can produce considerable morbidity resulting from painful skin lesions, alopecia, disfigurement, etc. Skin lesions in patients with lupus may be specific (LE specific) or may be non specific (LE non specific). Acute cutaneous LE (Lupus specific) has a strong association with systemic disease and non-specific skin lesions always indicate disease activity for which patients present to rheumatologists and internists. Therefore, a thorough understanding of the cutaneous manifestations of SLE is essential for most efficient management. The aims of this study were to evaluate the patterns and prevalence of skin lesions in patients with SLE and to assess the relationship between skin lesions and other systemic involvement. At the Department of Rheumatology and Clinical Immunology, IPGME&R in Kolkata, 150 patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatology Association (updated 1982) were examined and followed-up for cutaneous manifestations between January 2002 and January 2007. Skin lesions were important clinical features. About 45 patients (30%) presented with skin lesions although all patients had skin lesions during the follow-up period. Skin changes noted were as follows: Lupus specific lesions: malar rash in 120 patients (80%), photosensitive dermatitis in 75 patients (50%), generalized maculopapular rash in 40 patients (26.67%), discoid rash in 30 patients (20%), subacute cutaneous lupus erythematosus (SCLE) in 5 patients (3.34%), lupus profundus in 5 patients (3.34%). The lupus non-specific lesions were non-scarring alopecia in 130 patients (86.67%), oral ulcers in 85 patients (56.67%), vasculitic lesions in 50 patients (33.34%), bullous lesions in 15 patients (10%), Raynaud's phenomenon in 10 patients (6.67%), pyoderma gangrenosum in 2 patients (1.34%), erythema multiforme in 10 patients (6.67%), and nail fold infarcts in 2 patients (1.34%); however, mucosal discoid lupus, lichenoid discoid lupus, livedo reticularis, sclerodactyly, etc. were not detected. Patients having lupus-specific skin lesions e.g., malar rash were associated with systemic involvement, whereas those having lupus non-specific skin lesions were associated with disease flare. Skin lesions in patients with SLE are important disease manifestations and proper understanding is essential for diagnosis and efficient management.

A report on the clinical-pathological correlations of 788 gingival lesion

PubMed Central

Carbone, Mario; Broccoletti, Roberto; Carcieri, Paola; Conrotto, Davide; Carrozzo, Marco; Arduino, Paolo G.

2017-01-01

Background The diagnosis and treatment of a variety of non-plaque related gingival diseases have become an integrated aspect of everyday dentistry. The aim of this study was to analyse the relationship between clinical appearance and histopathological features of gingival lesions in a large Northern Italian population. Material and Methods A retrospective study of 788 cases of gingival and alveolar mucosal biopsies was set up. Statistical analysis was performed by calculating the odds ratio and 95% confidence interval (C.I.), in order to assess the degree of association between the clinical parameters considered (primary lesions) and the single pathologies, statistically evaluated by Mantel-Haenszel tests. The correlation between clinical and histological diagnosis was classified as follow: 1) expected data (ED): provisional clinical diagnosis; 2) real data (RD): final histopathology diagnosis; 3) concordant data (CD): correspondence between the expected data and real data. The correlation was calculated as follow: CC (complete concordance) = CD x 100 / ED, this expressing the percentage in which the clinical and the histological diagnosis overlapped. Results The most frequently observed and biopsied primary lesions resulted to be exophytic, followed by mucosal colour changes and finally by losses of substance. The statistically significant association between primary lesion and their manifestation in gingival pathologies was reported. Volume increases, for instance, were positively correlated to plasma cell epulis, pyogenic granuloma, fibrous reactive hyperplasia and hemangioma. Verrucous-papillary lesions were most often seen in verrucous carcinoma, verrucous leukoplakia and mild dysplasia. White lesion resulted to be related to leukoplakia or oral lichen planus. Red lesions resulted to be related only oral lichen planus. Erosive vesicle-bullous lesions were linked to disimmune pathologies. Ulcerative lesions were positively associated to oral squamous cell cancer. Finally, potentially malignant disorders have the most percentage high concordance. Among the malignant lesions, the correlation increased up to the squamous cell carcinoma and leukaemia. Conclusions This article presented the frequency and the clinico-pathological concordance of all primary lesions and the histopathological diagnosis of gingival lesions. For every primary lesion, it is possible to correlate a specific histopathological diagnosis in a statistical manner. This can be a valuable aid for not specialist clinicians who daily observe mucosae and have the opportunity to intercept major diseases. Key words:Gingival lesions; clinical appearance; histological analysis; clinico-pathological correlation. PMID:29053652

Anti-Interleukin-6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis-Associated Uveitis Refractory to Anti-Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty-Five Patients.

PubMed

Calvo-Río, Vanesa; Santos-Gómez, Montserrat; Calvo, Inmaculada; González-Fernández, M Isabel; López-Montesinos, Berta; Mesquida, Marina; Adán, Alfredo; Hernández, María Victoria; Maíz, Olga; Atanes, Antonio; Bravo, Beatriz; Modesto, Consuelo; Díaz-Cordovés, Gisela; Palmou-Fontana, Natalia; Loricera, Javier; González-Vela, M C; Demetrio-Pablo, Rosalía; Hernández, J L; González-Gay, Miguel A; Blanco, Ricardo

2017-03-01

To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)-associated uveitis. We conducted a multicenter study of patients with JIA-associated uveitis that was refractory to conventional immunosuppressive drugs and anti-tumor necrosis factor (anti-TNF) agents. We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1-5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 μm to 259.1 ± 39.5 μm after 6 months of TCZ (P = 0.012). The best-corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow-up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and bullous impetigo in 1 patient. TCZ appears to be a useful therapy for severe refractory JIA-associated uveitis. © 2016, American College of Rheumatology.

Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region: an open-label, randomised, controlled, non-inferiority trial.

PubMed

Bowen, Asha C; Tong, Steven Y C; Andrews, Ross M; O'Meara, Irene M; McDonald, Malcolm I; Chatfield, Mark D; Currie, Bart J; Carapetis, Jonathan R

2014-12-13

Impetigo affects more than 110 million children worldwide at any one time. The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial resistance. Few trials of systemic antibiotics are available to guide management of extensive impetigo. As such, we aimed to compare short-course oral co-trimoxazole with standard treatment with intramuscular benzathine benzylpenicillin in children with impetigo in a highly endemic setting. In this randomised, controlled, non-inferiority trial, Indigenous Australian children aged 3 months to 13 years with purulent or crusted non-bullous impetigo were randomly assigned (1:1:1) to receive benzathine benzylpenicillin (weight-banded injection), twice-daily co-trimoxazole for 3 days (4 mg/kg plus 20 mg/kg per dose), or once-daily co-trimoxazole for 5 days (8 mg/kg plus 40 mg/kg per dose). At every visit, participants were randomised in blocks of six and 12, stratified by disease severity. Randomisation was done by research nurses and codes were in sealed, sequentially numbered, opaque envelopes. Independent reviewers masked to treatment allocation compared digital images of sores from days 0 and 7. The primary outcome was treatment success at day 7 in a modified intention-to-treat analysis. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000858291. Between Nov 26, 2009, and Nov 20, 2012, 508 patients were randomly assigned to receive benzathine benzylpenicillin (n=165 [156 analysed]), twice-daily co-trimoxazole for 3 days (n=175 [173 analysed]), or once-daily co-trimoxazole for 5 days (n=168 [161 analysed]). Treatment was successful in 133 (85%) children who received benzathine benzylpenicillin and 283 (85%) who received pooled co-trimoxazole (absolute difference 0·5%; 95% CI -6·2 to 7·3), showing non-inferiority of co-trimoxazole (10% margin). Results for twice-daily co-trimoxazole for 3 days and once-daily co-trimoxazole for 5 days were similar. Adverse events occurred in 54 participants, 49 (90%) of whom received benzathine benzylpenicillin. Short-course co-trimoxazole is a non-inferior, alternative treatment to benzathine benzylpenicillin for impetigo; it is palatable, pain-free, practical, and easily administered. Australian National Health and Medical Research Council. Copyright © 2014 Elsevier Ltd. All rights reserved.