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Sample records for mycosis fungoides bullosa

  1. [Disseminated mycosis fungoides].

    PubMed

    Trope, B M; Schmidt, J M; de Oliveira Neto, A A; Pereira Júnior, A C; Marques, A de S; Ishida, C E; Azulay, R D

    1985-01-01

    A case of mycosis fungoides (MF) that began with cutaneous eritemato-papular lesions leading to death with neurological symptoms is reported. Cutaneous histophatology was typical to MF and the liquoric citology showed Sézary cells. Necropsy evidenced extra-cutaneous dissemination of the tumor involving lymphnodes, heart, digestive system, bladder, liver, bone marrow and leptomeninges. The uncommon clinical manifestations and evolution are discussed.

  2. Gastrointestinal complications of mycosis fungoides.

    PubMed Central

    Slater, D N; Bleehen, S S; Beck, S

    1984-01-01

    Mycosis fungoides (MF) is an uncommon T-cell lymphoma which characteristically involves the skin. Two patients with MF are described who developed fatal complications secondary to involvement of the gastrointestinal tract. One developed malabsorption due to small intestinal involvement; the other had a massive haemorrhage from an ulcerated nodule of tumour in the stomach. The potential for extracutaneous spread is discussed, and it is emphasized that bowel infiltration should be considered in any patient with MF who develops gastrointestinal symptoms or complications. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. PMID:6737393

  3. Pembrolizumab in Treating Patients With Relapsed or Refractory Stage IB-IVB Mycosis Fungoides or Sezary Syndrome

    ClinicalTrials.gov

    2017-01-31

    Recurrent Mycosis Fungoides and Sezary Syndrome; Stage IB Mycosis Fungoides and Sezary Syndrome; Stage IIA Mycosis Fungoides and Sezary Syndrome; Stage IIB Mycosis Fungoides and Sezary Syndrome; Stage IIIA Mycosis Fungoides and Sezary Syndrome; Stage IIIB Mycosis Fungoides and Sezary Syndrome; Stage IVA Mycosis Fungoides and Sezary Syndrome; Stage IVB Mycosis Fungoides and Sezary Syndrome

  4. Verrucous presentation in patients with mycosis fungoides.

    PubMed

    Schlichte, Megan J; Talpur, Rakhshandra; Venkatarajan, Sangeetha; Curry, Jonathan L; Nagarajan, Priyadharsini; Duvic, Madeleine

    2016-03-01

    Mycosis fungoides is a potentially fatal skin condition whose variable clinical appearance may mimic a variety of benign, inflammatory dermatoses, making it a diagnostic challenge. Three patients with mycosis fungoides, treated with multiple approved topical and systemic therapies, presented with acquired verrucous lesions on the extremities. The verrucous presentation of mycosis fungoides is one of the many atypical forms of the disease, with a paucity of documented cases in the medical literature. Although rare, verrucous and hyperkeratotic lesions in mycosis fungoides may increase the risk of considerable diagnostic delay if clinicians do not maintain a high degree of suspicion in cases of acquired verrucous lesions in the appropriate clinical setting. © 2015 The International Society of Dermatology.

  5. Clinicopathologic Variants of Mycosis Fungoides.

    PubMed

    Muñoz-González, H; Molina-Ruiz, A M; Requena, L

    2017-04-01

    Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. The clinical course of the disease is typically characterized by progression from a nonspecific phase of erythematous macules to the appearance of plaques and ultimately, in some patients, tumors. However, numerous clinical and histopathologic variants of MF with specific therapeutic and prognostic implications have been described in recent decades. Clarification of the differential diagnosis can be frustrated by the wide range of clinical manifestations and histopathologic patterns of cutaneous infiltration, particularly in the early phases of the disease. In this paper, we review the main clinical, histopathologic, and immunohistochemical characteristics of the variants of MF described in the literature in order to facilitate early diagnosis of the disease.

  6. Mycosis fungoides. Electron beam therapy.

    PubMed

    Spittle, M F

    1977-01-01

    The most effective treatment of late mycosis fungoides is total skin electron beam therapy. The beam at the Hammersmith Hospital in London has been adapted to treat these patients. Patients with advanced disease who have failed more conservative methods of treatment are irradiated. The electron beam is modified by the use of carbon and copper scatterers to produce an 80 percent depth dose at 5.5, 8 and 11.5 millimeters below the skin surface. The dose achieved in most patients is between 1500 rads and 2600 rads given in 10 to 13 treatments over 5-7 weeks. Recently the higher dose range has been employed and lithium flouride studies have shown that giving these doses from each of 4 fields, the dose achieved on the skin is approximately twice the given dose. The management of patients and the effects of treatment are discussed.

  7. Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

    ClinicalTrials.gov

    2017-04-13

    Recurrent Mycosis Fungoides and Sezary Syndrome; Refractory Mycosis Fungoides; Stage IB Mycosis Fungoides and Sezary Syndrome; Stage II Mycosis Fungoides and Sezary Syndrome; Stage IIA Mycosis Fungoides and Sezary Syndrome; Stage IIB Mycosis Fungoides and Sezary Syndrome; Stage III Mycosis Fungoides and Sezary Syndrome; Stage IIIA Mycosis Fungoides and Sezary Syndrome; Stage IIIB Mycosis Fungoides and Sezary Syndrome; Stage IV Mycosis Fungoides and Sezary Syndrome; Stage IVA Mycosis Fungoides and Sezary Syndrome; Stage IVB Mycosis Fungoides and Sezary Syndrome

  8. Emerging treatment options for early mycosis fungoides

    PubMed Central

    Fernandez-Guarino, Montserrat

    2013-01-01

    Mycosis fungoides is a candidate for skin-directed therapies in its initial stages. In recent years, therapeutic options outside of the normal treatment recommendations such as topical imiquimod, topical tazarotene, topical methotrexate, excimer light sources, and photodynamic therapy have been published with variable results. These alternatives have been useful in cases of localized mycosis fungoides that do not respond to routine treatments; nevertheless, more studies on these methods are still needed. This article summarizes the literature and data that are known so far about these treatments. PMID:23450851

  9. Granulomatous mycosis fungoides - A diagnostic challenge*

    PubMed Central

    Pousa, Catharina Maria Freire de Lucena; Nery, Natália Solon; Mann, Danielle; Obadia, Daniel Lago; Alves, Maria de Fátima Gonçalves Scotelaro

    2015-01-01

    Granulomatous mycosis fungoides is a rare subtype of T-cell cutaneous lymphoma. Due to its clinical heterogenicity the diagnosis is delayed and based on histopathological and immuno-histochemical findings, sometimes requiring gene rearrangement studies for confirmation. We report the case of a patient who was submitted to several biopsies before diagnostic conclusion. PMID:26375225

  10. Mycosis fungoides: an important differential diagnosis for acquired palmoplantar keratoderma.

    PubMed

    Kim, Janet; Foster, Rachael; Lam, Minh; Kumarasinghe, Sujith Prasad

    2015-02-01

    Mycosis fungoides is the most common subtype of primary cutaneous lymphoma and has several clinical variants. We report a 74-year-old man presenting with an acquired palmoplantar keratoderma initially diagnosed and treated as psoriasis with suboptimal improvement. Several months later the patient developed patches and plaques that were histologically consistent with mycosis fungoides. These lesions were ameliorated with the treatment of the underlying mycosis fungoides and the palmoplantar keratoderma resolved promptly with radiotherapy. This case highlights the importance of considering mycosis fungoides as an infrequent but serious cause of acquired palmoplantar keratoderma.

  11. [Normolipemic plane xanthomas and mycosis fungoides].

    PubMed

    García-Arpa, Mónica; Rodríguez-Vázquez, María; Vera, Elena; Romero, Guillermo; González-García, Jesús; Cortina, Pilar

    2005-06-01

    Diffuse normolipemic plane xanthomas are characterized by the presence of yellowish plaques on the eyelids, neck, upper trunk, buttocks and flexures. Histology shows foamy histiocytes in the dermis. Approximately half of all cases are associated with hematological disorders. On rare occasions, they have been described in the context of cutaneous T-cell lymphomas. We present the case of a female patient with tumor-stage mycosis fungoides who developed normolipemic plane xanthomas coinciding with the appearance of new lymphoma lesions. We review English-language literature regarding the rare association of xanthomas and cutaneous T-cell lymphomas.

  12. Childhood Hypopigmented Mycosis Fungoides: A Rare Diagnosis

    PubMed Central

    Garcez, Carla; Leite, Filipa; Oliva, Tereza; Santos, António; Pinto, Armando

    2016-01-01

    Primary cutaneous lymphomas (PCL) are rare in pediatrics. Mycosis fungoides (MF) is the most frequent PCL diagnosed in childhood. There are various clinical variants of MF, including the hypopigmented MF (HMF). We present a 5-year-old boy with an 18-month history of progressive, generalized, nonpruritic hypopigmented lesions with central lacy erythema. He had no improvement with emollients. Skin biopsy showed typical features of HMF. He was treated with topical corticosteroids and tacrolimus and narrow-band ultraviolet B (NBUVB) phototherapy, with good response. HMF may mimic multiple skin disorders. Unusual hypopigmented skin lesions should be biopsied. Though phototherapy is effective, recurrence is common. PMID:28025633

  13. Interleukin-12 and Interleukin-2 in Treating Patients With Mycosis Fungoides

    ClinicalTrials.gov

    2013-01-15

    Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome

  14. Diagnostics in mycosis fungoides and Sezary syndrome

    PubMed Central

    Olek-Hrab, Karolina; Silny, Wojciech

    2013-01-01

    Aim The aim of this paper was to present diagnostic methods helping in the recognition of mycosis fungoides (MF) and Sezary syndrome (SS). Background Mycosis fungoides is the most common form of primary cutaneous T-cell lymphomas. It is characterized by a distinctive long-term course and malignant T-cell proliferation. MF diagnosis is not easy, mainly due to the atypical clinical presentation of the disease at an early stage. Materials and methods Low specific changes, which can be observed at the histopathological examination. Initially, the skin lesions may resemble psoriasis, atopic dermatitis or chronic eczema. Patients are qualified according to the available, and generally accepted WHO-EORTC classification, based on a combination of clinical and histopathological markers. From a clinical point of view, it is also important to carry out the qualification according to the TNMB assessment, which allows to specify the stage of the disease, and is helpful in the monitoring of the course of disease and therapeutic effects. Results In this paper we try to present currently available diagnostic methods. Conclusion Diagnosis of MF and SS still causes many problems due to less characteristic changes in the early stage of disease and requires wide interdisciplinary knowledge. PMID:24936324

  15. Borderline tuberculoid leprosy mimicking mycosis fungoides.

    PubMed

    Rodríguez-Acosta, Elva Dalia; Esquivel-Pedraza, Lilly; Saeb-Lima, Marcela; Arenas-Guzmán, Roberto; Granados-Arriola, Julio; Domínguez-Cherit, Judith

    2013-01-01

    A 65-year-old unemployed man, originally from Michoacán and currently living in Toluca, state of Mexico, presented for medical consultation for disseminated dermatosis in all body segments. The condition was limited to the head and neck, was bilateral and symmetrical, and was characterized by infiltrated and confluent erythematous-edematous plates of diverse diameter covering 90% of the upper and lower extremities (Figure 1). The ailment had 2 years' evolution and a progressive course. The patient was diagnosed in private practice as having atopic dermatitis. After exacerbation of symptoms, he was treated with deflazacort and hydroxychloroquine with no improvement. Results from lesion biopsies revealed sarcoidal granulomas and the patient was therefore referred to the dermatology department at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán for further study and treatment with the presumptive diagnosis of mycosis fungoides vs sarcoidosis.

  16. Management Strategies for Mycosis Fungoides in India

    PubMed Central

    Raychaudhury, Tanumay

    2017-01-01

    Mycosis fungoides is the most common primary cutaneous T-cell lymphoma. The approach to diagnosis and further follow-up is outlined. Evidence for interventions is based classically on a Tumor Node Metastasis Blood TNMB “stage-based” approach. The treatment options in India are limited. The options as per risk stratification and prognostic index are discussed. Early stages and low-risk patients can be managed with expectant policy or skin-directed therapies including topical steroids and phototherapy; intermediate-risk patients can be opted for interferons or retinoids or low dose methotrexate along with radiotherapy including total skin electron beam therapy while high-risk patients are managed most often with single agent or multiagent palliative chemotherapy. Patients who are intermediate- or high-risk need management by a multispecialty team at tertiary care centers. PMID:28400632

  17. [Immunological studies on patients with mycosis fungoides].

    PubMed

    Greiding, L; Mathov, E; Casalá, A; Borda, J M; Slazer, M; Núñez, J; Antonowicz, E

    1975-01-01

    Recently, much has been published on the immunological status of patients affected with various lymphomas. In the particular case of Mycosis fungoide, there was no general agreement on the immunological status of the corresponding patients. In fact, López Borrasca et al, found severe depression of cellular immunity in such patients. On the contrary, Blaylock and Clendenning found very little change in cellular immunity, but a very high serum-IgA. We want to offer our experience on this problem with the immunological survey of four patients with the Alibert-Bazin-form of Mycosis fungoide. The following tests were performed on each patient: a) Intracutaneous test with candidina, PPD and other bacterial antigens. b) Sensitization to a concentrate solution of dinitrochlorobencene (DNCB). c) Lymphocyte Transformation Test (LTT), with phytohemagglutinin as mitogen. d) Quantitative determination of IgG, IgM, IgA and beta1C, with the radial immunodiffusion technique (Mancini et al.). e) Agar immunoelectrophoresis. The following results were obtained: 1) The cellular immunity was markedly depressed in the four patients when any of a, b or c-test was performed. 2) All the patients showed very high levels of serum IgA, 150% higher than control. The reason for this is unknown. On the contrary, IgG in serum was less elevated and IgM and beta1C serum levels were normal. 3) No monoclonal bands were found in any case (immunoelectrophoresis). 4) No definite conclusions could be reached due to the limited number of cases, but the uniformity of results should encourage to carry this work further.

  18. Mycosis Fungoides (Including Sézary Syndrome) Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Mycosis fungoides and Sézary syndrome are neoplasias of malignant T lymphocytes that affect the skin. Learn about the clinical presentation, prognosis, staging, and treatment for mycosis fungoides and Sézary syndrome in this expert-reviewed summary.

  19. New aspects of the clinicopathological features and treatment of mycosis fungoides and Sézary syndrome.

    PubMed

    Furue, Masutaka; Kadono, Takafumi

    2015-10-01

    Mycosis fungoides and Sézary syndrome are T-helper (Th)2-skewed cutaneous lymphomas. The clinical course of mycosis fungoides is classically indolent, manifesting as patches, plaques and tumors. Along with their progression, Th2 dominance tends to be accelerated. In this review, we discuss the epidemiology, clinicopathogenetic features and therapeutic approaches in mycosis fungoides and Sézary syndrome.

  20. Podoplanin Expression Correlates with Disease Progression in Mycosis Fungoides.

    PubMed

    Jankowska-Konsur, Alina; Kobierzycki, Christopher; Grzegrzółka, Jędrzej; Piotrowska, Aleksandra; Gomulkiewicz, Agnieszka; Glatzel-Plucinska, Natalia; Reich, Adam; Podhorska-Okołów, Marzenna; Dzięgiel, Piotr; Szepietowski, Jacek C

    2017-02-08

    The aim of this study was to investigate the role of lymphangiogenesis in the clinical progression and outcome of mycosis fungoides. Immunohistochemistry and Western blot techniques were used to assess the expression of podoplanin and vascular endothelial growth factor C in mycosis fungoides. Expression of vascular endothelial growth factor C measured by immunohistochemistry was significantly higher in mycosis fungoides samples in comparison with control cases (chronic benign dermatoses) (p = 0.0012). Increased expression of podoplanin was found in advanced vs. early mycosis fungoides (p < 0.0001), and was positively correlated with cutaneous and nodal involvement (p < 0.001, p < 0.0001; respectively). Higher podoplanin expression was also significantly associated with shorter survival (p < 0.001). Strong positive correlation was observed between expression of podoplanin analysed by immunohistochemistry and Western blot (r = 0.75, p < 0.0001). A similar association was shown regarding expression of vascular endothelial growth factor C (r = 0.68, p = 0.0007). In conclusion, these results suggest that increased expression of podoplanin is associated with poor clinical course, as well as shorter survival, of patients with mycosis fungoides.

  1. Cutaneous malignant melanoma in association with mycosis fungoides.

    PubMed

    Evans, Alun V; Scarisbrick, Julia J; Child, F J; Acland, Katharine M; Whittaker, Sean J; Russell-Jones, Robin

    2004-05-01

    We retrospectively analyzed the first 461 cases entered into our cutaneous lymphoma database and found 285 cases of mycosis fungoides. We also identified 6 cases of malignant melanoma, all of which were found in patients with mycosis fungoides. The crude rate of melanoma in the general population in England, United Kingdom, in 1998 was 8.8/100,000 in men and 11.4/100,000 in women. The incidence of melanoma found in our cohort of patients with mycosis fungoides was far higher, and in 4 of the 6 patients cannot be explained on the basis of prior therapy. The reason for this association is unclear, but this report emphasizes the risk of second malignancies for patients with cutaneous T-cell lymphoma and melanoma.

  2. Secondary Cutaneous Amyloidosis in a Patient with Mycosis Fungoides.

    PubMed

    Nam, Chan Hee; Park, Min Kee; Choi, Mi Soo; Hong, Seung Phil; Park, Byung Cheol; Kim, Myung Hwa

    2017-02-01

    Secondary cutaneous amyloidosis refers to clinically unapparent amyloid deposits within the skin in association with a pre-existing skin condition or skin tumors, such as basal cell carcinoma, porokeratosis, solar elastosis, Bowen's disease, and mycosis fungoides. A 70-year-old woman presented with a 6-month history of asymptomatic multiple yellowish plaques on both legs. She had been diagnosed with mycosis fungoides 7 years ago and was treated with psoralen and ultraviolet A radiation (PUVA) therapy, narrow-band ultraviolet B (UVB) therapy, and acitretin for 5 years. Finally, she reached complete remission of mycosis fungoides. However, new yellowish lesions started to appear 1 year after discontinuing the phototherapy. A physical examination revealed multiple yellowish plaques on both extremities. The plaques were well circumscribed and slightly elevated. All laboratory tests were normal. A biopsy specimen showed multiple nodular deposits of eosinophilic amorphous material in papillary dermis and upper reticular dermis. The deposits represented apple green birefringence on Congo red stain viewed under polarized light. Acellular small nodules in the upper dermis consisted of randomly oriented, non-branching, 6.67~12.7 nm thick amyloid fibrils on electron microscopy. We report an interesting and rare case of secondary cutaneous amyloidosis after narrow-band UVB therapy and PUVA therapy in a patient with mycosis fungoides.

  3. Secondary Cutaneous Amyloidosis in a Patient with Mycosis Fungoides

    PubMed Central

    Nam, Chan Hee; Park, Min Kee; Choi, Mi Soo; Hong, Seung Phil; Park, Byung Cheol

    2017-01-01

    Secondary cutaneous amyloidosis refers to clinically unapparent amyloid deposits within the skin in association with a pre-existing skin condition or skin tumors, such as basal cell carcinoma, porokeratosis, solar elastosis, Bowen's disease, and mycosis fungoides. A 70-year-old woman presented with a 6-month history of asymptomatic multiple yellowish plaques on both legs. She had been diagnosed with mycosis fungoides 7 years ago and was treated with psoralen and ultraviolet A radiation (PUVA) therapy, narrow-band ultraviolet B (UVB) therapy, and acitretin for 5 years. Finally, she reached complete remission of mycosis fungoides. However, new yellowish lesions started to appear 1 year after discontinuing the phototherapy. A physical examination revealed multiple yellowish plaques on both extremities. The plaques were well circumscribed and slightly elevated. All laboratory tests were normal. A biopsy specimen showed multiple nodular deposits of eosinophilic amorphous material in papillary dermis and upper reticular dermis. The deposits represented apple green birefringence on Congo red stain viewed under polarized light. Acellular small nodules in the upper dermis consisted of randomly oriented, non-branching, 6.67~12.7 nm thick amyloid fibrils on electron microscopy. We report an interesting and rare case of secondary cutaneous amyloidosis after narrow-band UVB therapy and PUVA therapy in a patient with mycosis fungoides. PMID:28223751

  4. Multiple squamous cell carcinomas in a patient with mycosis fungoides.

    PubMed

    Le, Katie; Lim, Adrian; Samaraweera, Ushma; Morrow, Christine; See, Adrian

    2005-11-01

    A 51-year-old man with type IV skin presented for evaluation of a generalized rash associated with multiple ulcerated, nodular lesions on his legs. The nodular lesions occurred approximately 18 months after the initial onset of generalized rash, which had been diagnosed as plaque/patch stage mycosis fungoides. He continued to develop further nodular lesions on his trunk in the weeks following presentation. The nodular lesions were shown to be squamous-cell carcinoma on histopathology. He had received only topical hydrocortisone prior to the development of the second cutaneous malignancy and had no past exposure to carcinogens. His squamous cell carcinomas were treated with surgical excision and split-skin grafting. He received total skin electron-beam therapy to treat the mycosis fungoides. Second malignancy in mycosis fungoides is a recognized phenomenon and usually occurs after potentially carcinogenic therapy. This case demonstrates the occurrence of second malignancy in the absence of a precipitating factor, suggesting that there are innate, immune-mediated mechanisms in the development of cancer in patients with mycosis fungoides.

  5. Mycosis fungoides and Kaposi’s sarcoma association in an HIV-negative patient*

    PubMed Central

    Bariani, Maria Carolina Prado Fleury; Fleury Júnior, Luiz Fernando Fróes; Ribeiro, Ana Maria Quinteiro; Carneiro, Siderley de Souza; Pereira, Tiago Arantes

    2016-01-01

    The association of mycosis fungoides and kaposi’s sarcoma in HIV-negative patients is a rare phenomenon. The presence of human herpesvirus 8 (HHV-8) – associated with all forms of Kaposi’s sarcoma – has also been recently identified in mycosis fungoides lesions. However, a causal association between HHV-8 and the onset of mycosis fungoides has not been established yet. The present case reports a patient who developed Kaposi’s sarcoma lesions after a two-year UVB phototherapy to treat a mycosis fungoides. Negative immunohistochemistry staining for Kaposi’s sarcoma-associated herpesvirus in the initial mycosis fungoides lesions strengthens the absence of a link between Kaposi’s sarcoma-associated herpesvirus and mycosis fungoides. Immunosuppression caused by the lymphoma and prolonged phototherapy were probably the contribut ing factors for the onset of Kaposi’s sarcoma. PMID:28300912

  6. Mycosis fungoides and Sézary syndrome: clinical, histopathological and immunohistochemical review and update*

    PubMed Central

    Yamashita, Thamy; Abbade, Luciana Patricia Fernandes; Marques, Mariangela Esther Alencar; Marques, Silvio Alencar

    2012-01-01

    This paper reviews the diagnostic and classificatory concepts of mycosis fungoides and Sézary syndrome in light of the latest normative publications. It describes the great variability of the clinical expression of mycosis fungoides in its early stages as well as the histopathological and immunohistochemical aspects that help with diagnosis. The diagnostic criteria required for characterizing Sézary syndrome and the staging system used for both mycosis fungoides and Sézary syndrome are described. PMID:23197199

  7. Adult pityriasis lichenoides-like mycosis fungoides: a clinical variant of mycosis fungoides.

    PubMed

    de Unamuno Bustos, Blanca; Ferriols, Amparo P; Sánchez, Rosa B; Rabasco, Ana G; Vela, Carmen G; Piris, Miguel A; Alegre de Míquel, Víctor

    2014-11-01

    Mycosis fungoides (MF) is the most frequent type of cutaneous T cell lymphoma. Its clinicopathological spectrum is wide, and the resulting diversity makes it difficult to establish a differential diagnosis among pityriasis lichenoides (PL), lymphomatoid papulosis (LyP), and atypical MF. This study describes four patients with longstanding PL-like lesions, in whom clinicopathological correlations contributed towards the establishment of definitive diagnoses of MF. The clinical histories of the four patients were reviewed. Skin biopsies were processed by hematoxylin and eosin staining and immunohistochemical techniques. Disease spread was studied according to laboratory tests, complete blood counts, biochemical parameters, lactate dehydrogenase, lymphocyte populations, and Sézary cells. Thoracoabdominopelvic computed tomography was performed. The four patients included two women and two men, aged 35-70 years, all of whom had chronic skin lesions located mainly on the trunk and extremities. In three patients, initial clinicopathological correlations led to the diagnosis of PL; further biopsies were required to diagnose MF. In all patients, the atypical lymphocytic infiltrate showed a lichenoid or perivascular distribution with focal epidermotropism and parakeratosis. All cases proved positive for CD4 and CD3, and negative for CD20, CD8, and CD30. Polymerase chain reaction showed monoclonal-type T cells in one and polyclonal infiltrates in three patients. All patients were initially treated with topical corticosteroids and photochemotherapy. None of the treatments proved completely successful, but subsequent tests have yielded no evidence of disease progression in any patient. In patients with clinical features of longstanding PL and histological findings consistent with MF, differential diagnosis must include PL, LyP, and papular MF. As some forms of PL evolve towards MF and PL-like forms of MF, these patients should undergo regular follow-up and repeated biopsies

  8. Home ultraviolet phototherapy of early mycosis fungoides: preliminary observations.

    PubMed

    Milstein, H J; Vonderheid, E C; Van Scott, E J; Johnson, W C

    1982-03-01

    Thirty-one patients with early mycosis fungoides (MF) and three patients with parapsoriasis en plaques were treated with ultraviolet phototherapy (280 to 350 nm) at home using a commercially available light source containing four Westinghouse FS40 lamps. A complete clinical and histologic remission of disease, lasting for a median duration in excess of 18 months, was achieved in nineteen patients (61%) with MF. Although higher complete response rates generally are achieved with other therapeutic modalities, ultraviolet phototherapy with its minimal adverse effects may be indicated for selected patients. Controlled studies are encouraged to evaluate the full potential of conventional phototherapy in the management of MF.

  9. CD8-positive Mycosis Fungoides Masquerading as Pyoderma Gangrenosum

    PubMed Central

    Saha, Maitrayee; Jain, Bhawna Bhutoria; Chattopadhyay, Sarbani; Podder, Indrashis

    2016-01-01

    Mycosis fungoides (MF), a primary cutaneous T-cell lymphoma, accounts for <1% of non-Hodgkin lymphomas. The diagnosis of classic MF is based on a constellation of typical clinical presentation, histopathology, immunohistochemistry, and T-cell monoclonality detected by molecular studies. Rarely, atypical clinical presentation may occur. The typical immunohistochemical phenotype is, CD2 +ve, CD3 +ve, CD5 +ve, CD4 +ve, and CD8 − ve. Here, we report a rare case of CD8 +ve MF in a 43-year-male patient who was clinically diagnosed as pyoderma gangrenosum initially. The atypical presentation and rarity of such case have prompted this report. PMID:27688458

  10. Immunocytochemical characterisation of cutaneous lymphomas other than mycosis fungoides.

    PubMed Central

    Ralfkiaer, E; Saati, T A; Bosq, J; Delsol, G; Gatter, K C; Mason, D Y

    1986-01-01

    The immunophenotypic properties of 25 cutaneous non-Hodgkin lymphomas other than mycosis fungoides or Sezary syndrome were investigated and correlated with clinical and histopathological data. The 11 low grade lymphomas were all of B cell origin, whereas the 14 high grade lymphomas comprised B and T cell tumours, true histiocytic proliferations, and one "nul" cell lymphoid neoplasm. For the high grade lymphomas correct prediction of the immunological phenotype based on morphological criteria was only possible in three cases. In contrast, all of the low grade lymphomas showed the non-epidermotropic infiltration pattern considered to be characteristic of cutaneous B cell tumours. For these conditions, however, immunophenotypic investigations provided a convenient means of improving discrimination between benign (polyclonal) and malignant (monoclonal) lesions, and also showed similarities with nodal lymphomas in terms of expression of lymphoid subset markers and composition of the non-neoplastic white cell infiltrate. No differences were identified between primary and secondary or concurrent cutaneous and extracutaneous lymphomas. Cutaneous non-Hodgkin lymphomas other than mycosis fungoides or Sezary syndrome constitute a heterogeneous group of neoplasms and most of these disorders are likely to represent cutaneous equivalents of nodal malignancies. Immunophenotypic investigations form a useful supplement to their histogenetic characterisation and may provide a common conceptual basis for their classification. Images PMID:3522633

  11. Co-existence of various clinical and histopathological features of mycosis fungoides in a young female.

    PubMed

    Naeini, Farahnaz Fatemi; Soghrati, Mehrnaz; Abtahi-Naeini, Bahareh; Najafian, Jamshid; Rajabi, Parvin

    2015-01-01

    Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL) and a rare disorder that typically affects older adults with erythematous scaling patches and plaques. Hypopigmented patches are a rare clinical variant of the disease. Granulomatous mycosis fungoides (GMF) is also a rare type of CTCL. No particular clinical criteria are available for the diagnosis of GMF, because of its variable presentations, and so the detection of GMF is primarily considered as a histopathological diagnosis. Rarely, a co-existence of more than one clinical or histopathological feature of mycosis fungoides may be present. To the best of our knowledge this is the first report of MF that shows the simultaneous co-existence of more than one clinical and histopathological variant of MF. We present a 29-year-old female with clinical presentations of both classic and hypopigmented mycosis fungoides (MF), and also the histopathological features of the classic and granulomatous types of the disease.

  12. Clinical case of the month. A young man with a persistent skin eruption. Mycosis fungoides.

    PubMed

    Kendrick, Christina G; Gerdes, Michelle S; Lopez, Fred A; McBurney, Elizabeth I

    2004-01-01

    There are many types of skin disease that fit into the classification of cutaneous lymphoma, but mycosis fungoides is by far the most common of this group. It is a non-Hodgkin's lymphoma of T-cell origin that presents in the skin. Mycosis fungoides often evolves for years without a specific diagnosis because it can present as an eczematous or psoriasiform eruption. Patients identified in the early stages and treated appropriately have a normal life expectancy.

  13. Childhood hypopigmented mycosis fungoides: a commonly delayed diagnosis

    PubMed Central

    Gameiro, Ana; Gouveia, Miguel; Tellechea, Óscar; Moreno, Ana

    2014-01-01

    Primary cutaneous lymphomas (PCLs) are exceedingly rare in children and adolescents, with mycosis fungoides (MF) being the most frequent PCL diagnosed in childhood. There are numerous unusual clinical variants of MF, including the hypopigmented type form (HMF). HMF is exceptional overall, but comparatively common among children. We present an 8-year-old boy with a 3-year history of progressive, generalised, scaly, hypopigmented round patches and few erythematous papules. He was first diagnosed with pityriasis alba (PA), and moisturisers were prescribed with no improvement. Skin biopsy showed typical features of MF, and the patient was successfully treated with narrowband ultraviolet B. HMF may simulate atopic dermatitis, PA, pityriasis lichenoides, tinea versicolour, vitiligo, postinflammatory hypopigmentation or leprosy. Therefore, persistent and unusual hypopigmented lesions should be biopsied to rule out this rare variant of MF. PMID:25538219

  14. Childhood hypopigmented mycosis fungoides: a commonly delayed diagnosis.

    PubMed

    Gameiro, Ana; Gouveia, Miguel; Tellechea, Óscar; Moreno, Ana

    2014-12-23

    Primary cutaneous lymphomas (PCLs) are exceedingly rare in children and adolescents, with mycosis fungoides (MF) being the most frequent PCL diagnosed in childhood. There are numerous unusual clinical variants of MF, including the hypopigmented type form (HMF). HMF is exceptional overall, but comparatively common among children. We present an 8-year-old boy with a 3-year history of progressive, generalised, scaly, hypopigmented round patches and few erythematous papules. He was first diagnosed with pityriasis alba (PA), and moisturisers were prescribed with no improvement. Skin biopsy showed typical features of MF, and the patient was successfully treated with narrowband ultraviolet B. HMF may simulate atopic dermatitis, PA, pityriasis lichenoides, tinea versicolour, vitiligo, postinflammatory hypopigmentation or leprosy. Therefore, persistent and unusual hypopigmented lesions should be biopsied to rule out this rare variant of MF. 2014 BMJ Publishing Group Ltd.

  15. Granulomatous mycosis fungoides with hypohidrosis mimicking lepromatous leprosy.

    PubMed

    Gutte, Rameshwar; Kharkar, Vidya; Mahajan, Sunanda; Chikhalkar, Siddhi; Khopkar, Uday

    2010-01-01

    Granulomatous mycosis fungoides (GMF) is a rare type of cutaneous T cell lymphoma. A 38-year-old married male presented with decreased sweating all over the body for last 8 years, progressive redness and scaling over body for 2 years and multiple noduloulcerative lesions over the body for 1 year. Cutaneous examination revealed generalized erythema and scaling with poikilodermatous changes over chest and upper back along with multiple noduloulcerative lesions. Skin biopsy from a nodular lesion revealed dense granulomatous infiltrate of atypical lymphocytes with epidermotropism and sparing of appendages. Diagnosis of GMF was made. Computed tomographic scan of thorax, abdomen and pelvis revealed axillary and inguinal lymphadenopathy. Immunohistochemistry revealed leukocyte common antigen and CD3 positivity suggestive of T cell origin. Patient was started on CHOP (Cyclophosphamide, Hydroxydaunorubicin, Oncovin and Prednisolone) regimen of chemotherapy with marked improvement after three cycles of chemotherapy. This case had some clinical resemblance to lepromatous leprosy.

  16. TP53 Gene Status Affects Survival in Advanced Mycosis Fungoides

    PubMed Central

    Wooler, Gitte; Melchior, Linea; Ralfkiaer, Elisabeth; Rahbek Gjerdrum, Lise Mette; Gniadecki, Robert

    2016-01-01

    TP53 is frequently mutated in different types of neoplasms including leukemia and lymphomas. Mutations of TP53 have also been reported in mycosis fungoides (MF), the most common type of cutaneous lymphoma. However, little is known about the frequency, spectrum of mutations, and their prognostic significance in MF. In this study, we have optimized the protocol for Sanger sequencing of TP53 using DNA extracted from archival paraffin-embedded biopsies. Of 19 samples from patients with stage IIB MF or higher, 31% harbored mutations in TP53. Overall survival of the patients with mutated TP53 was significantly shorter than median survival in the age- and stage-matched patients treated in our Institution. Distribution of mutations was heterogenous in TP53 exons; however, C > T transitions were common suggesting the causal role of ultraviolet radiation. We propose that TP53 mutation status would be useful for risk stratification of patients with advanced MF. PMID:27891503

  17. Evaluation of cardiovascular disease risk factors in patients with mycosis fungoides*

    PubMed Central

    Cengiz, Fatma Pelin; Emiroglu, Nazan

    2015-01-01

    BACKGROUND Mycosis fungoides, the most common subtype of cutaneous T-cell lymphoma, is more common in patients aged 45-55. OBJECTIVE Cardiovascular risk factors have been investigated in several skin diseases. However, the relation between cardiovascular diseases and mycosis fungoides remains unclear. Therefore, the aim of this study was to assess cardiovascular risk factors in patients with mycosis fungoides. METHODS 32 patients with mycosis fungoides and 26 healthy controls were enrolled in the study. Glucose, total cholesterol, high-density lipoprotein cholesterol, triglyceride, homocystein, high sensitivity C-reactive protein, low-density lipoprotein – cholesterol, were measured in the sera of patients. RESULTS Patients had significantly higher high-sensitivity C-reactive protein, homocysteine, low-density lipoprotein - cholesterol, total cholesterol (p= 0.032) (p< 0.001) (p= 0.001) (p< 0.001). There was a positive correlation between the levels of homo-cysteine and total cholesterol (p= 0.001, r = +0.431). Additionally, a significantly positive correlation was found between the levels of high-sensitivity C-reactive protein and low-density lipoprotein - cholesterol (p= 0.014, r = +0.320) in patient group. CONCLUSIONS Patients with mycosis fungoides had significantly higher levels of total-cholesterol, low-density lipoprotein -cholesterol, homocysteine and high-sensitivity C-reactive protein than healthy subjects. The present study has demonstrated an increased rate of cardiovascular risk in patients with mycosis fungoides. Even though the etiology of these associations is elusive, dermatologists should be sensitized to investigate metabolic derangements in patients with mycosis fungoides, in order to lessen mortality and comorbidity with a multidisciplinary approach. PMID:25672297

  18. Folliculotropic Mycosis Fungoides: Clinical and Histologic Features in Five Patients.

    PubMed

    Ehsani, Amir Hooshang; Azizpour, Arghavan; Noormohammadpoor, Pedram; Seirafi, Hasan; Farnaghi, Farshad; Kamyab-Hesari, Kambiz; Sharifi, Mehdi; Nasimi, Maryam

    2016-01-01

    Alopecia can be a manifestation of mycosis fungoides (MF); however, the prevalence is unknown. We sought to describe the clinicopathologic presentation of alopecia in patients with diagnosis of MF. A retrospective analysis of patients with biopsy-proven MF, who were evaluated at our cancer center from 2002 to 2012, was performed to identify patients with alopecia. Five patients with alopecia were identified from reviewing of 157 patients with MF. The male:female ratio was 3:2, and the mean age of patients was 42.8 years. Two of these patients showed patchy hair loss on scalp which was clinically identical to alopecia areata. In remaining three patients, hair loss was seen in areas of MF lesions, and epidermal changes consisted of patch- and plaque-type lesions of MF, tumors, and follicular lesions (follicular MF) were also present. In two of these patients, lymphadenopathy without any visceral involvement was detected. Alopecia was observed in 5 (3.18%) patients with MF, which makes it a rare finding, which included alopecia areata-like patchy loss in 2 and alopecia within MF lesions in 3.

  19. ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOR MYCOSIS FUNGOIDES AND SEZARY SYNDROME

    PubMed Central

    Lechowicz, Mary Jo; Lazarus, Hillard M.; Carreras, Jeanette; Laport, Ginna G.; Cutler, Corey S.; Wiernik, Peter H.; Hale, Gregory A.; Maharaj, Dipnarine; Gale, Robert Peter; Rowlings, Phillip A.; Freytes, César O; Miller, Alan M.; Vose, Julie M.; Maziarz, Richard T.; Montoto, Silvia; Maloney, David G.; Hari, Parameswaran N.

    2014-01-01

    We describe outcomes after allogeneic hematopoietic cell transplantation (HCT) for mycosis fungoides and sezary syndrome (MF/SS). Outcomes of 129 subjects with MF/SS reported to the Center for the International Blood and Marrow Transplant (CIBMTR) from 2000–2009. Median time from diagnosis to transplant was 30 (4–206) months and most subjects were with multiply relapsed/refractory disease. Majority (64%) received non-myeloablative conditioning (NST) or reduced intensity conditioning (RIC). NST/RIC recipients were older in age compared to myeloablative recipients (median age 51 vs. 44 y p= 0.005) and transplanted in recent years. Non-relapse mortality (NRM) at 1 and 5 years was 19% (95 % CI 12–27%) and 22% (95 % CI 15–31%) respectively. Risk of disease progression was 50% (95% CI 41–60%) at 1 year and 61% (95% CI 50–71%) at 5 years. Progression free survival (PFS) at 1 and 5 years was 31% (95% CI 22–40%) and 17% (95% CI 9–26%) respectively. Overall survival at 1 and 5 years was 54% (95% CI 45–63%) and 32% (95% CI 22–44%) respectively. Allogeneic HCT in MF/SS results in 5 year survival in approximately one-third of patients and of those, half of them remain disease-free. PMID:25068422

  20. Whole-genome sequencing reveals oncogenic mutations in mycosis fungoides

    PubMed Central

    McGirt, Laura Y.; Jia, Peilin; Baerenwald, Devin A.; Duszynski, Robert J.; Dahlman, Kimberly B.; Zic, John A.; Zwerner, Jeffrey P.; Hucks, Donald; Dave, Utpal; Zhao, Zhongming

    2015-01-01

    The pathogenesis of mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is unknown. Although genetic alterations have been identified, none are considered consistently causative in MF. To identify potential drivers of MF, we performed whole-genome sequencing of MF tumors and matched normal skin. Targeted ultra-deep sequencing of MF samples and exome sequencing of CTCL cell lines were also performed. Multiple mutations were identified that affected the same pathways, including epigenetic, cell-fate regulation, and cytokine signaling, in MF tumors and CTCL cell lines. Specifically, interleukin-2 signaling pathway mutations, including activating Janus kinase 3 (JAK3) mutations, were detected. Treatment with a JAK3 inhibitor significantly reduced CTCL cell survival. Additionally, the mutation data identified 2 other potential contributing factors to MF, ultraviolet light, and a polymorphism in the tumor suppressor p53 (TP53). Therefore, genetic alterations in specific pathways in MF were identified that may be viable, effective new targets for treatment. PMID:26082451

  1. Immunohistopathological Study of c-FLIP Protein in Mycosis Fungoides

    PubMed

    Rezk Hassan, Ghada Fawzy; Marey, Karima

    2017-09-27

    Background: Mycosis fungoides (MF) is the commonest variant of primary cutaneous T cell lymphoma with several clinicopathologic variants. Defective apoptotic mechanism may be important in the pathogenesis and progression of MF. c-FLIP protein is an important anti-apoptotic marker and chemotherapeutic resistant factor. This study aimed to evaluate the c-FLIP expression in MF and its role in the pathogenesis of MF. Methods: Twenty patients of MF and ten normal persons were included in this study. Skin biopsies were obtained from both patients and controls. They were studied and examined immunohistochemically for the expression of CD4 and c-FLIP. Results: c-FLIP expression was significantly increased in patients when compared to controls in both epidermis and dermis. There were positive correlations between c-FLIP expression and CD4+ expression in both epidermal and dermal lesions of patients group. There were statistically significant positive correlations between c-FLIP expression (in both dermal and epidermal lesions) and the age of patients. c-FLIP expression increased with the tumor progression but with no statistical significance. Conclusion: Defective regulation of apoptosis has been considered as a main cause for accumulation of clonal T cells, and it was related to an increased expression of c-FLIP which may have a role in the pathogenesis of MF. Also, c-FLIP may have prognostic information in MF as its level increased with both age of the patients and tumor progression. Creative Commons Attribution License

  2. CD20 positive mycosis fungoides: a case report.

    PubMed

    Sen, Filiz; Kang, Steven; Cangiarella, Joan; Kamino, Hideko; Hymes, Kenneth

    2008-04-01

    CD20 positive T-cell lymphoma is extremely rare. Most reported cases are nodal peripheral T-cell lymphomas (PTCLs) or rarely lymphoma involving extranodal sites. Only two cases of CD20 positive T-cell lymphomas involving the skin have been previously reported and were classified as PTCL - not otherwise specified. We present a case report of a 53-year-old man with CD20 positive mycosis fungoides (MF) involving the skin and an inguinal lymph node. The patient presented with erythematous patches and plaques of the right lower extremity and was found to have an enlarged inguinal lymph node 2 years later. Flow cytometric immunophenotyping of the lymph node aspirate showed a CD2+/CD3+/CD4+/CD5+/CD7-/CD8- T-cell population with CD20 co-expression. Molecular studies by polymerase chain reaction demonstrated clonal T-cell receptor gamma chain gene rearrangement. Immunoglobulin heavy and light chain gene rearrangements were not identified. To our knowledge, this is the first case of CD20 positive MF involving a lymph node to be reported in the literature.

  3. Folliculotropic Mycosis Fungoides: Clinical and Histologic Features in Five Patients

    PubMed Central

    Ehsani, Amir Hooshang; Azizpour, Arghavan; Noormohammadpoor, Pedram; Seirafi, Hasan; Farnaghi, Farshad; Kamyab-Hesari, Kambiz; Sharifi, Mehdi; Nasimi, Maryam

    2016-01-01

    Background: Alopecia can be a manifestation of mycosis fungoides (MF); however, the prevalence is unknown. Aims: We sought to describe the clinicopathologic presentation of alopecia in patients with diagnosis of MF. Methods: A retrospective analysis of patients with biopsy-proven MF, who were evaluated at our cancer center from 2002 to 2012, was performed to identify patients with alopecia. Results: Five patients with alopecia were identified from reviewing of 157 patients with MF. The male:female ratio was 3:2, and the mean age of patients was 42.8 years. Two of these patients showed patchy hair loss on scalp which was clinically identical to alopecia areata. In remaining three patients, hair loss was seen in areas of MF lesions, and epidermal changes consisted of patch- and plaque-type lesions of MF, tumors, and follicular lesions (follicular MF) were also present. In two of these patients, lymphadenopathy without any visceral involvement was detected. Conclusions: Alopecia was observed in 5 (3.18%) patients with MF, which makes it a rare finding, which included alopecia areata-like patchy loss in 2 and alopecia within MF lesions in 3. PMID:27688448

  4. Bullous pemphigoid. Occurrence in a patient with mycosis fungoides receiving PUVA and topical nitrogen mustard therapy

    SciTech Connect

    Patterson, J.W.; Ali, M.; Murray, J.C.; Hazra, T.A.

    1985-04-01

    A 57-year-old woman with mycosis fungoides developed blisters within cutaneous plaques while receiving PUVA therapy and topical nitrogen mustard. Direct and indirect immunofluorescence studies showed the findings of bullous pemphigoid. Her bullous disease was controlled after cessation of these therapies and institution of prednisone and methotrexate. During the 5 months following completion of a course of electron-beam therapy, she has been free of the cutaneous manifestations of both diseases. Previous instances of PUVA-related pemphigoid have occurred in psoriatics. The role of ultraviolet light in the induction of pemphigoid is discussed, particularly with regard to its possible interaction with the altered skin of psoriasis or mycosis fungoides. Some of the rare cases of bullous mycosis fungoides might actually have represented ultraviolet-unmasked bullous pemphigoid.

  5. Excimer laser in the treatment of mycosis fungoides.

    PubMed

    Deaver, Darcie; Cauthen, Ashley; Cohen, George; Sokol, Lubomir; Glass, Frank

    2014-06-01

    Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents as a patch or plaque in early-stage disease. Phototherapy including psoralen plus ultraviolet A and ultraviolet B are well-established treatment modalities in management of early-stage MF. Only a limited number of reports have evaluated the efficacy of 308-nm excimer laser in therapy of cutaneous T-cell lymphoma. We sought to evaluate the efficacy of 308-nm excimer laser (XTRAC, PhotoMedex, Montgomeryville, PA) in patients with stage IA to IIA MF. We reviewed the clinical and laboratory characteristics of 6 consecutive patients given the diagnosis of refractory MF who underwent treatment with excimer laser. We found that the 308-nm excimer laser is a safe and well-tolerated alternative therapy for early-stage MF. In addition, we were able to delineate criteria to help predict treatment response. Our data showed that 4 (66%) patients achieved clinical improvement (3 complete responses, 1 partial response), 1 had stable disease, and 1 had progressive disease. This was a retrospective study consisting of 6 patients. A prospective study with a larger sample size would be desirable for future studies. The use of 308-nm excimer laser in the treatment of stage IA to IIA MF showed clinical and pathological benefit for patients with isolated lesions or lesions in areas that may be difficult to treat because of anatomic location. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  6. Cutaneous expression of Thy-1 in mycosis fungoides.

    PubMed Central

    Fivenson, D. P.; Douglass, M. C.; Nickoloff, B. J.

    1992-01-01

    Dermal dendritic cells from eleven cases of mycosis fungoides (MF) (six patch and five plaque stage), two cases of pre-MF, and five specimens of normal human skin, were characterized immunohistochemically using a panel of antibodies including anti-human Thy-1, intercellular adhesion molecule-1 (ICAM-1; CD54), endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD1a, CD2, CD14, CD18, CD34, MAC387, KP-1, EBM-11, factor XIIIa, factor XIIIs, and S100. Thy-1 expression in normal skin was limited to the microvascular endothelium and perivascular dendritic cells. An extensive interstitial network of Thy-1+ dendritic cells was seen in the papillary dermis of all cases of MF, whereas no epidermal cells were Thy-1+. The mean +/- standard deviation of interstitial Thy-1+ cells per high power field in the dermis was: normal skin, 2.86 +/- 0.34; pre-MF, 15; patch stage MF, 13.4 +/- 7.08; plaque stage MF, 49.96 +/- 21.29. Thy-1+ dendritic cells morphologically resembled the factor XIIIa+ "dermal dendrocyte" (DD) and shared their VCAM-1+, ICAM-1+, CD1a, CD2-, CD14+, CD18+, EMB11+, factor XIIIa+, factor XI-IIs-, S100-, MAC387- and KP-1-immunophenotype in MF. Double labeling studies revealed up to 50% of Thy-1+DD were also factor XIIIa+ in MF. Immediately beneath these cells was a similar network of CD34+, Thy-1-, factor XIIIa- dendritic cells limited to the reticular dermis. Strong microvascular endothelial cell expression of Thy-1 and VCAM-1, and focal vascular ELAM-1 expression were also seen in MF. Distinct cellular compartmentalization (papillary dermis versus reticular dermis versus epidermis) of dendritic cells is demonstrated by the differential expression of Thy-1, factor XIIIa, and CD34 antigens. The extensive number and prominent dermal dendritic network in the papillary dermis juxtaposed between epidermal keratinocytes (KC) and dermal/epidermal T cells, suggests an important pathophysiologic role for this newly recognized and

  7. Mycosis fungoides mimicking nevoid hyperkeratosis of the nipple and areola in an adolescent.

    PubMed

    Yalçın, Başak; Gür, Güneş; Tabanlıoğlu-Onan, Duru; Ekici, Özlem

    2014-01-01

    Mycosis fungoides is one of the great imitators in dermatology; it can mimic many dermatoses. Nevoid hyperkeratosis of the nipple and areola is a rare idiopathic disease with typical clinical features of verrucous thickening and brownish discoloration of the nipple, areola or both. Here, a 16-year-old male patient with mycosis fungoides mimicking nevoid hyperkeratosis of the nipple and areola has been reported. To our knowledge, this is the first atypical MF patient to have presented with a NHNA-like lesion. Although the clinical appearance of nevoid hyperkeratosis of the nipple and areola is highly characteristic for diagnosis, histopathological examination is recommended, especially in cases with atypical features such as unexpected age, male gender and unilateral location.

  8. Case-control study of possible causative factors in mycosis fungoides

    SciTech Connect

    Tuyp, E.; Burgoyne, A.; Aitchison, T.; MacKie, R.

    1987-02-01

    A detailed case control study was carried out on 53 patients (33 males and 20 females) with histologically proven mycosis fungoides and on an age- and sex-matched control population. Possible causative factors investigated included occupation, recreation, and exposure to petrochemicals, pesticides, insecticides, and potential carcinogens. Exposure to plants of the Compositae family, tanning history, and chronic sun exposure were also investigated, as were smoking history, drug ingestion history, and other skin disease. Personal and family histories of other malignancies were also investigated. The only statistically significant difference to emerge was that the patients with mycosis fungoides had significantly more family history of atopic dermatitis. In view of the absence of any significant difference between patients and controls with regard to personal history of atopic dermatitis, this difference may be the result of multiple statistical testing rather than a phenomenon of true biological significance.

  9. Successful treatment of syringotropic CD8+ mycosis fungoides accompanied by hypohidrosis with vorinostat and retinoids.

    PubMed

    Kakizaki, Aya; Fujimura, Taku; Mizuashi, Masato; Watabe, Akiko; Kambayashi, Yumi; Aiba, Setsuya

    2013-11-01

    We describe a 34-year-old Japanese man with syringotropic CD8+ mycosis fungoides (MF) accompanied by hypohidrosis who was treated with vorinostat and retinoids. Interestingly, immunohistochemical staining for dermcidin revealed a decrease of sweat in the eccrine glands, and a sweat test by the iodine starch method proved hypohidrosis in the MF-affected areas. Six months after treatment with this combination therapy, the patient's advanced MF was under control.

  10. Recalcitrant tinea corporis as the presenting manifestation of patch-stage mycosis fungoides.

    PubMed

    Hubert, Jason N; Callen, Jeffrey P

    2003-01-01

    Mycosis fungoides is a cutaneous T-cell lymphoma. Its presence, which denotes an altered immune system, may make treatment of otherwise simple cutaneous infections difficult. In the case presented here, a patient with widespread tinea corporis poorly responsive to several oral antifungals was noted as having a background poikilodermatous slightly scaly eruption. Results of a skin biopsy during therapy with oral antifungal medications showed evidence of tinea corporis; atrophy of the epidermis; a superficial, perivascular, and interstitial lymphocytic infiltrate with numerous atypical lymphocytes; and exocytosis of atypical lymphocytes into the epidermis with formation of microabscesses-findings consistent with the diagnosis of mycosis fungoides. Treatment with PUVA (oral psoralen and UVA light) and oral itraconazole led to long-term remission of the mycosis fungoides and the associated tinea corporis. Immune suppression may have contributed to the recalcitrant nature of our patient's dermatophyte infection. Underlying cutaneous, systemic, or iatrogenic disorders associated with immune dysfunction should be considered in patients with recalcitrant dermatophyte infections.

  11. The treatment of mycosis fungoides and related conditions with particular emphasis on electron therapy.

    PubMed Central

    Szur, L.

    1975-01-01

    The difficulties created by the lack of generally accepted views on classification, diagnostic criteria and natural history of the cutaneous lymphomata are discussed. Only the lymphomata which remain confined to the skin throughout the major part of their development are considered. It is emphasized that these are extremely radiosensitive and that there must be some factors as yet unknown which play a part in their unique natural history and response to treatment. The cutaneous lymphomata are considered under three headings: (1) lymphocytoma, (2) lymphosarcoma and reticulum cell sarcoma, (3) mycosis fungoides. The characteristics of the first two are discussed briefly and illustrative examples are given. The relatively benign nature of the lymphocytoma is stressed. It is suggested that the solitary lymphosarcoma of the skin should be treated by radical radiotherapy since long-term survival or cure may be achieved. The treatment of mycosis fungoides is considered in greater detail. The physical advantages of electron therapy are described and details given of whole body surface treatment with electrons produced by a 6 MeV linear accelerator and slowed down with carbon decelerators of appropriate thickness. The results in 73 patients treated by electrons are analysed. The early and late side-effects are mentioned and the necessity for investigating other forms of treatment is stressed. It is concluded that at the present time electron therapy is the most satisfactory form of treatment for mycosis fungoides. Images Fig. 1 Fig. 2 Fig. 3 Fig. 9 PMID:810153

  12. A case of advanced mycosis fungoides with comprehensive skin and visceral organs metastasis: sensitive to chemical and biological therapy.

    PubMed

    Liu, Yi-Qian; Zhu, Wei-You; Shu, Yong-Qian; Gu, Yan-Hong

    2012-08-01

    Mycosis fungoides is a common cutaneous T-cell lymphoma, which is usually characterized by chronic, indolence progression, with absence of typical symptoms in early stage, metastasis to lymph nodes, bone marrow and visceral organs in later stage and ultimately progression to systemic lymphoma. It can result in secondary skin infection which is a frequent cause of death. At present, no curative therapy existed. Therapeutic purpose is to induce remission, reduce tumor burden and protect immune function of patients. A case of patient with advanced severe mycosis fungoides receiving CHOP plus interferon α-2a was reported here, with disease-free survival of 7 months and overall survival of over 17.0 months, and current status as well as developments of mycosis fungoides were briefly introduced.

  13. Periostin in the Cancer Stroma of Mycosis Fungoides Palmaris et Plantaris: A Case Report and Immunohistochemical Study

    PubMed Central

    Tanita, Kayo; Fujimura, Taku; Kakizaki, Aya; Furudate, Sadanori; Mizuashi, Masato; Watabe, Akiko; Aiba, Setsuya

    2016-01-01

    Mycosis fungoides palmaris et plantaris (MFPP) is a rare variant of mycosis fungoides limited to the palms and soles. Although little is known about the pathogenesis of MFPP, this variant of mycosis fungoides presents a relatively good prognosis. In this report, we describe an 85-year-old Japanese man with MFPP. Immunohistochemical staining revealed the dense deposition of periostin in the cancer stroma, as well as infiltration of CD163+CD206− tumor-associated macrophages (TAMs), which suggested the phenotypes of TAMs were not polarized to the M2 phenotype in the lesional skin of MFPP. Our present case might suggest one of the possible reasons for the good prognosis of MFPP. PMID:27293391

  14. Mycosis Fungoides of the Oral Cavity: Fungating Tumor Successfully Treated with Electron Beam Radiation and Maintenance Bexarotene

    PubMed Central

    Miranda, Roberto N.; Emge, Drew A.; DiCicco, Beau A.; Lewis, Daniel J.

    2016-01-01

    Oral involvement in mycosis fungoides is unusual and portends a poor prognosis. The clinical findings of three new cases are described along with a differential diagnosis and review of the literature. For brevity, only one patient is discussed in detail below whereas the other two cases are solely described in table form. The patient had a four-year history of mycosis fungoides before developing an exophytic tongue tumor. He was treated with local electron beam radiation and is disease-free to date while being on maintenance therapy with oral bexarotene. Analysis of the data collected from our review of the literature and the present cases reveal key insights. PMID:28074163

  15. Extracorporeal Photopheresis in the Treatment of Mycosis Fungoides and Sézary Syndrome.

    PubMed

    Zic, John A

    2015-10-01

    Extracorporeal photopheresis (ECP) is an immunomodulating procedure that leads to an expansion of peripheral blood dendritic cell populations and an enhanced TH1 immune response in cutaneous T-cell lymphoma (CTCL). Because of its excellent side effect profile and moderate efficacy, ECP is considered first-line therapy for erythrodermic mycosis fungoides (MF) and Sézary syndrome. Patients with a measurable but low blood tumor burden are most likely to respond to ECP, and the addition of adjunctive immunostimulatory agents may also increase response rates. There may be a role for ECP in the treatment of refractory early stage MF, but data are limited.

  16. Hypopigmented Mycosis Fungoides: Clinical, Histological, and Immunohistochemical Remission Induced by Narrow-band Ultraviolet B

    PubMed Central

    Bisherwal, Kavita; Singal, Archana; Pandhi, Deepika; Sharma, Sonal

    2017-01-01

    Mycosis fungoides (MF) is the most common type of primary cutaneous lymphomas. Several clinical variants of MF have been described. Purely, hypopigmented variant of MF (HMF) is rare. Phototherapy, especially photochemotherapy (Psoralen and ultraviolet), is the most widely used method and is recommended as the first-line treatment for HMF. However, there are no standard guidelines for phototherapy as the disease is uncommon. We, hereby, report a 30-year-old woman with HMF in whom clinical, histopathological, and immunohistochemical remission was achieved following narrow-band ultraviolet B therapy. PMID:28400643

  17. A Rare Case of Mycosis Fungoides in the Oral Cavity and Small Intestine Complicated by Perforation

    PubMed Central

    Emge, Drew Arthur; Bassuner, Juri; Lewis, Daniel J.; Duvic, Madeleine

    2016-01-01

    Extracutaneous involvement in mycosis fungoides (MF) carries a poor prognosis. Oral and gastrointestinal (GI) tract lesions are both rare locations of disease. We describe the clinical findings of one case with oral and GI MF complicated by perforation after systemic antineoplastic treatment, and review the relevant literature. The patient had a 1-year history of MF before development of tongue and palate tumors. He was treated with local electron beam radiation, but re-presented to the hospital after what was found to be small intestine perforation following systemic antineoplastic therapy. The case reveals key insights into the progression and complications of lymphomas with GI tract involvement. PMID:27920681

  18. Mycosis fungoides staged by 18F-flurodeoxyglucose positron emission tomography/computed tomography

    PubMed Central

    Xu, Lu; Pang, Hua; Zhu, Jin; Chen, Xi; Guan, Lili; Wang, Jie; Chen, Jing; Liu, Ying

    2016-01-01

    Abstract Introduction: Mycosis fungoides is a kind of malignant lymphoma arising from T cells, but primarily occurs in skin, and it is the most common type of cutaneous lymphoma. Mycosis fungoides (MF) is a rare non-Hodgkin lymphoma but the most common type of primary cutaneous T-cell lymphomas. Because of unknown etiology and mechanism, and lack of typical clinical and histophysiological manifestations, the final diagnosis of MF is currently dependent on pathology and immunohistochemistry. Subsequently, tumor staging is very important. Different approaches would be taken according to varying degrees of cutaneous and extracutaneous lesions. Computed tomography (CT) scan has been chosen to stage tumors customarily. However, CT could only provide morphological information and analyze lymphadenopathy by the size criteria. 18F-flurodeoxyglucose positron emission tomography/computed tomography (PET/CT) could provide morphological information and metabolic conditions simultaneously, which is helpful to locate and stage lesion. Conclusion: 18F-flurodeoxyglucose PET/CT could identify cutaneous and extracutaneous lesions in patients with MF. It could provide the range of lesions and biopsy target. PMID:27828842

  19. Mycosis Fungoides electron beam absorbed dose distribution using Fricke xylenol gel dosimetry

    NASA Astrophysics Data System (ADS)

    da Silveira, Michely C.; Sampaio, Francisco G. A.; Petchevist, Paulo C. D.; de Oliveira, André L.; Almeida, Adelaide de

    2011-12-01

    Radiotherapy uses ionizing radiation to destroy tumor cells. The absorbed dose control in the target volume is realized through radiation sensors, such as Fricke dosimeters and radiochromic film, which permit to realize bi-dimensional evaluations at once and because of that, they will be used in this study as well. Among the several types of cancer suitable for ionizing radiation treatment, the Mycosis Fungoides, a lymphoma that spreads on the skin surface and depth, requires for its treatment total body irradiation by high-energy electrons. In this work the Fricke xylenol gel (FXG) was used in order to obtain information about the absorbed dose distribution induced by the electron interactions with the irradiated tissues and to control this type of treatment. FXG can be considered as an alternative dosimeter, since up to now only films have been used. FXG sample cuvettes, simulating two selected tomos (cranium and abdomen) of the Rando anthropomorphic phantom, were positioned along with radiochromic films for comparison. The phantom was subjected to Stanford total body irradiation using 6 MeV electrons. Tomographic images were acquired for both dosimeters and evaluated through horizontal and vertical profiles along the tomographic centers. These profiles were obtained through a Matlab routine developed for this purpose. From the obtained results, one could infer that, for a superficial and internal patient irradiation, the FXG dosimeter showed an absorbed dose distribution similar to the one of the film. These results can validate the FXG dosimeter as an alternative dosimeter for the Mycosis Fungoides treatment planning.

  20. Catalase, carbonic anhydrase and xanthine oxidase activities in patients with mycosis fungoides.

    PubMed

    Cengiz, Fatma Pelin; Beyaztas, Serap; Gokce, Basak; Arslan, Oktay; Guler, Ozen Ozensoy

    2015-04-01

    Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma. In several studies the relationship between catalase (CAT), human cytosolic carbonic anhydrases (CA; hCA-I and hCA-II) and xanthine oxidase (XO) enzyme activities have been investigated in various types of cancers but carbonic anhydrase, catalase and xanthine oxidase activities in patients with MF have not been previously reported. Therefore, in this preliminary study we aim to investigate CAT, CA and XO activities in patients with MF. This study enrolled 32 patients with MF and 26 healthy controls. According to the results, CA and CAT activities were significantly lower in patients with mycosis fungoides than controls (p < 0.001) (p < 0.001). There was no significant difference in XO activity between patient and control group (p = 0.601). Within these findings, we believe these enzyme activity levels might be a potentially important finding as an additional diagnostic biochemical tool for MF.

  1. A Prospective, Open-Label Study of Low-Dose Total Skin Electron Beam Therapy in Mycosis Fungoides

    SciTech Connect

    Kamstrup, Maria R.; Specht, Lena; Skovgaard, Gunhild L.; Gniadecki, Robert

    2008-07-15

    Purpose: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. Methods and Materials: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years]) with histopathologically confirmed mycosis fungoides T2-T4 N0-N1 M0 who did not achieve complete remission or relapsed within 4 months after treatment with psoralen plus ultraviolet-A were included. Treatment consisted of low-dose total skin electron beam therapy administered at a total skin dose of 4 Gy given in 4 fractions over 4 successive days. Results: Two patients had a complete clinical response but relapsed after 3.5 months. Six patients had partial clinical responses, with a mean duration of 2.0 months. One patient had no clinical response. Median time to relapse was 2.7 months. One patient died of unrelated causes and did not complete treatment. Acute side effects included desquamation, xerosis, and erythema of the skin. No severe side effects were observed. Conclusion: Low-dose total skin electron beam therapy can induce complete and partial responses in Stage IB-II mycosis fungoides; however, the duration of remission is short. Low-dose total skin electron beam therapy may find application in palliative treatment of mycosis fungoides because of limited toxicity and the possibility of repeating treatments for long-term disease control.

  2. Romidepsin Controls Chronic Lymphocytic Leukemia in a Patient with Mycosis Fungoides

    PubMed Central

    Lemchak, David. M.; Akilov, Oleg. E.

    2016-01-01

    Romidepsin belongs to a class of medications called histone deacetylase inhibitors and is currently approved for treatment of cutaneous and peripheral T-cell lymphomas. Romidepsin was previously investigated for the treatment of chronic lymphocytic leukemia (CLL), and demonstrated potential benefit, but interest in its use declined following phase I clinical trials that showed poor tolerance of a significant side effect profile. We presented a patient with a history of stage II CLL, referred to dermatology for treatment of new-onset of mycosis fungoides (MF), who was treated with romidepsin over seven months. The patient achieved a partial response with 50% decrease in body surface area occupied by MF, thinning of remaining plaques, and near complete response in his CLL. His absolute lymphocyte count remained within the normal range for four months following discontinuation of romidepsin. Side effects were well-tolerated and did not limit therapy. Current literature on romidepsin is reviewed and compared to existing treatments for CLL. PMID:27994839

  3. Interstitial Mycosis Fungoides With Lichen Sclerosus-Like Clinical and Histopathological Features.

    PubMed

    Tekin, Burak; Kempf, Werner; Seckin, Dilek; Ergun, Tulin; Yucelten, Deniz; Demirkesen, Cuyan

    2016-02-01

    Mycosis fungoides (MF) simulates a variety of dermatologic disorders histopathologically and clinically, well deserving the designation of a great mimicker. Interstitial MF is a rare, but well-recognized histopathological variant resembling the interstitial form of granuloma annulare or the inflammatory phase of morphea. From a clinical standpoint, MF can have a wide array of manifestations, including an anecdotal presentation with lesions clinically suggestive of lichen sclerosus (LS). We herein report a 25-year-old man with a history of patch-stage MF who later developed widespread LS-like lesions histopathologically consistent with interstitial MF. In some biopsies, additional features resembling LS were discerned. We think that our case might represent a unique variant of interstitial MF presenting with LS-like lesions. The diagnostic challenge arising from this uncommon presentation is discussed together with review of the literature.

  4. A chart review of patients with early stage mycosis fungoides treated with psoralen plus UVA (PUVA).

    PubMed

    Soung, Jennifer; Muigai, Wangui; Amin, Nilam; Stern, Dana K; Lebwohl, Mark G

    2005-01-01

    PUVA has become a common form of treatment for early stage mycosis fungoides (MF). The purpose of this retrospective study was to review the clinical data of 51 MF patients (96% stage IA or IB) treated with PUVA at the Mt. Sinai MF clinic over the past 20 years. We analyzed the efficacy, safety, and remission duration in patients who were treated with a modified PUVA regimen. Forty-four of 51 patients (86%) achieved complete clinical clearing for all stages after initial PUVA therapy. The mean duration of remission with maintenance treatment was more than 27 months (range: 3 weeks to 130 months). The mean duration of disease from start of first PUVA therapy for all patients was 4.8 years (range: 0.7 to 130 months). PUVA for patients with early-stage MF is a safe and effective therapeutic modality with prolonged disease-free remissions, however, PUVA alone was not adequate for more advanced disease.

  5. Photodynamic therapy with the silicon phthalocyanine pc 4 induces apoptosis in mycosis fungoides and sezary syndrome.

    PubMed

    Lam, Minh; Lee, Yoojin; Deng, Min; Hsia, Andrew H; Morrissey, Kelly A; Yan, Chunlin; Azzizudin, Kashif; Oleinick, Nancy L; McCormick, Thomas S; Cooper, Kevin D; Baron, Elma D

    2010-01-01

    Our current focus on the effects of Photodynamic Therapy (PDT) using silicon phthalocyanine Pc 4 photosensitizer on malignant T lymphocytes arose due to preclinical observations that Jurkat cells, common surrogate for human T cell lymphoma, were more sensitive to Pc 4-PDT-induced killing than epidermoid carcinoma A431 cells. Mycosis fungoides (MF) as well as Sezary syndrome (SS) are variants of cutaneous T-cell lymphoma (CTCL) in which malignant T-cells invade the epidermis. In this study, we investigated the cytotoxicity of Pc 4-PDT in peripheral blood cells obtained from patients with SS and in skin biopsies of patients with MF. Our data suggest that Pc 4-PDT preferentially induces apoptosis of CD4(+)CD7(-) malignant T-lymphocytes in the blood relative to CD11b(+) monocytes and nonmalignant T-cells. In vivo Pc 4-PDT of MF skin also photodamages the antiapoptotic protein Bcl-2.

  6. Recommendations for treatment in folliculotropic mycosis fungoides: report of the Dutch Cutaneous Lymphoma Group.

    PubMed

    van Santen, S; van Doorn, R; Neelis, K J; Daniëls, L A; Horváth, B; Bruijn, M S; Sanders, C J G; van Rossum, M M; de Haas, E R M; Veraart, J C J M; Bekkenk, M W; Vermeer, M H; Willemze, R

    2017-07-01

    Folliculotropic mycosis fungoides (FMF) is an aggressive variant of mycosis fungoides (MF) and generally less responsive to standard skin-directed therapies (SDTs). Recent studies distinguished indolent (early-stage FMF) and more aggressive (advanced-stage FMF) subgroups. The optimal treatment for both subgroups remains to be defined. To evaluate initial treatment results in patients with early- and advanced-stage FMF. A study was undertaken of 203 patients (84 early-stage, 102 advanced-stage, 17 extracutaneous FMF) included in the Dutch Cutaneous Lymphoma Registry between 1985 and 2014. Type and results of initial treatment were retrieved from the Dutch Registry. Main outcomes were complete remission (CR); sustained complete remission; partial remission (PR), > 50% improvement; and overall response (OR; CR + PR). Patients with early-stage FMF were treated with nonaggressive SDTs in 67 of 84 cases resulting, respectively, in CR and OR of 28% and 83% for monotherapy topical steroids, 0% and 83% for ultraviolet B (UVB), and 30% and 88% for psoralen plus ultraviolet A (PUVA). In patients with advanced-stage FMF these SDTs were less effective (combined CR and OR 10% and 52%, respectively). In patients with advanced-stage FMF local radiotherapy (CR 63%; OR 100%), total skin electron beam irradiation (CR 59%; OR 100%) and PUVA combined with local radiotherapy (CR 5%, OR 75%) were most effective. The results of the present study demonstrate that not all patients with FMF should be treated aggressively. Patients with early-stage FMF may benefit very well from standard SDTs also used in early-stage classic MF and have an excellent prognosis. © 2017 British Association of Dermatologists.

  7. Mycosis fungoides after solid-organ transplantation: report of 2 new cases.

    PubMed

    Rodríguez-Gil, Yolanda; Palencia, Sara-Isabel; López-Ríos, Fernando; Ortiz, Pablo L; Rodríguez-Peralto, Jose L

    2008-04-01

    Long-term survival after solid-organ transplantation is increasing because of recent advances, including new immunosuppressive regimens to avoid graft rejection. However, the resultant modification of the immune system is associated with an increased risk of several cancers. The most common are skin cancers, and lymphomas are second in frequency. Nevertheless, posttransplant primary cutaneous lymphomas (PCLs) are rare, and their incidence is not well known currently. From the files of the Nephrology and Cardiology Departments of University Hospital "12 de Octubre" of Madrid, we obtained clinical data from 1612 transplanted patients and only found 2 cases of posttransplant PCLs, both were T-cell PCL. We reviewed the clinical, histopathological, and immunohistochemical characteristics; both cases were T-cell posttransplant PCLs manifested clinically as mycosis fungoides. One was a 57-year-old woman who had received a cadaveric kidney transplant, and the other was a 60-year-old man with a heart transplant. Histology and immunohistochemistry were consistent with the features of mycosis fungoides when lesions were completely developed. Up to 20% of all organ transplant recipients will suffer some form of malignancy. Unlike general population, 70% of PCLs in transplant recipients are B cell in origin and frequently show positivity for Epstein-Barr virus markers; whereas only 30% are cutaneous T-cell lymphomas. Different pathogenic hypothesis including reduced immune surveillance, chronic antigenic stimulation by transplant grafts, and the direct oncogenic effects of immunosuppressive drugs have been suggested. Although cutaneous B-cell lymphomas are more common, dermatopathologists should be aware that cutaneous T-cell lymphomas may also appear.

  8. STAT3/5-Dependent IL9 Overexpression Contributes to Neoplastic Cell Survival in Mycosis Fungoides

    PubMed Central

    Vieyra-Garcia, Pablo A.; Wei, Tianling; Naym, David Gram; Fredholm, Simon; Fink-Puches, Regina; Cerroni, Lorenzo; Odum, Niels; O'Malley, John T.; Gniadecki, Robert; Wolf, Peter

    2016-01-01

    Purpose Sustained inflammation is a key feature of mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL). Resident IL9–producing T cells have been found in skin infections and certain inflammatory skin diseases, but their role in MF is currently unknown. Experimental Design We analyzed lesional skin from patients with MF for the expression of IL9 and its regulators. To determine which cells were producing IL9, high-throughput sequencing was used to identify malignant clones and Vb-specific antibodies were employed to visualize malignant cells in histologic preparations. To explore the mechanism of IL9 secretion, we knocked down STAT3/5 and IRF4 by siRNA transfection in CTCL cell lines receiving psoralen+UVA (PUVA) ± anti-IL9 antibody. To further examine the role of IL9 in tumor development, the EL-4 T-cell lymphoma model was used in C57BL/6 mice. Results Malignant and reactive T cells produce IL9 in lesional skin. Expression of the Th9 transcription factor IRF4 in malignant cells was heterogeneous, whereas reactive T cells expressed it uniformly. PUVA or UVB phototherapy diminished the frequencies of IL9- and IL9r-positive cells, as well as STAT3/5a and IRF4 expression in lesional skin. IL9 production was regulated by STAT3/5 and silencing of STAT5 or blockade of IL9 with neutralizing antibodies potentiated cell death after PUVA treatment in vitro. IL9-depleted mice exhibited a reduction of tumor growth, higher frequencies of regulatory T cells, and activated CD4 and CD8 T lymphocytes. Conclusion Our results suggest that IL9 and its regulators are promising new targets for therapy development in mycosis fungoides. PMID:26851186

  9. Clinicopathological features of mycosis fungoides in patients exposed to Agent Orange during the Vietnam War.

    PubMed

    Jang, Min Soo; Jang, Jun Gyu; Han, Sang Hwa; Park, Jong Bin; Kang, Dong Young; Kim, Sang Tae; Suh, Kee Suck

    2013-08-01

    There are no reports on the clinicopathological features of mycosis fungoides (MF) among veterans exposed to Agent Orange, one of the herbicides used during the Vietnam War. To evaluate the clinical, histopathological and genotypic findings of Vietnam War veterans with MF and a positive history of exposure to Agent Orange, we performed a comparative clinicopathological study between MF patients with a history of Agent Orange exposure and those without a history of Agent Orange exposure. Twelve Vietnam War veterans with MF were identified. The mean interval from Agent Orange exposure to diagnosis was 24.5 years (range, 9-35). Skin lesions were significantly present on exposed and unexposed areas. Most patients (75%) experienced pruritus (mean visual analog scale score of 6.7). MF was manifested by plaques in 10 patients and by lichenification in five. Histopathological features of most cases were consistent with MF. Biopsy specimens also demonstrated irregular acanthosis (66.7%). In the comparative study, MF patients with a history of Agent Orange exposure differed significantly from those without exposure to Agent Orange in demographic and clinical characteristics. In addition, patients with exposure had an increased tendency for lesions in the exposed area. Notably, our patients showed a higher frequency (33.3%) of mycosis fungoides palmaris et plantaris than in previous studies. Histologically, irregular acanthosis was more frequently observed than ordinary MF. Our results indicate that dermatologists should pay close attention to these clinicopathological differences. Careful assessment of history of exposure to defoliants is warranted in some cases suspicious for MF. © 2013 Japanese Dermatological Association.

  10. Donor-derived mycosis fungoides following reduced intensity haematopoietic stem cell transplantation from a matched unrelated donor

    PubMed Central

    Kinsella, Francesca A M; Amel Kashipaz, Mohammad Rasoul; Scarisbrick, Julia; Malladi, Ram

    2017-01-01

    A 46-year-old woman with a history of dasatinib-resistant chronic myeloid leukaemia, clonal evolution and monosomy 7 underwent reduced intensity conditioned in vivo T-cell-depleted allogeneic haematopoietic stem cell transplantation (HSCT) from a matched unrelated donor. Following the transplantation, she developed recurrent cutaneous graft versus host disease (GvHD), which required treatment with systemic immunosuppression and electrocorporeal photophoresis. Concurrently, she developed a lichenoid rash with granulomatous features suggestive of cutaneous sarcoidosis. Additional treatment with hydroxychloroquine was initially successful, but 2 months later, she developed erythroderma with palpable lymphadenopathy. Repeated histological analysis established a diagnosis of folliculotropic mycosis fungoides stage IVA2, and the malignant clone was confirmed to be of donor origin. A positive response to brentuximab has been shown. This is the first reported case of primary mycosis fungoides after matched unrelated donor HSCT, and in a patient still undergoing treatment for GvHD. PMID:28073814

  11. Combined total body X-ray irradiation and total skin electron beam radiotherapy with an improved technique for mycosis fungoides

    SciTech Connect

    Halberg, F.E.; Fu, K.K.; Weaver, K.A.; Zackheim, H.S.; Epstein, E.H. Jr.; Wintroub, B.U.

    1989-08-01

    Twelve consecutive patients with advanced stage mycosis fungoides (MF) were treated with combined total body X ray irradiation (TBI) and total skin electron beam radiotherapy (EBRT). Six had generalized plaque disease and dermatopathic nodes, three had tumor stage disease and node biopsy positive for mycosis fungoides, and three had erythroderma/Sezary syndrome. The treatment regimen consisted of split course total body X ray irradiation, given in twice weekly 15 cGy fractions to 75 cGy, then total skin electron beam radiation therapy given in once weekly 400 cGy fractions to a total dose of 2400 cGy. Underdosed areas and areas of greatest initial involvement were boosted 400 cGy twice weekly for an additional 1200 cGy. This was followed by a second course of total body X ray irradiation, to a total dose of 150 cGy. The total skin electron beam radiotherapy technique is a modification of an established six position EBRT technique for mycosis fungoides. Measurements to characterize the beam with and without a lexan scattering plate, demonstrated that the combination of no-plate beams produced better dose uniformity with a much higher dose rate. This improved technique is particularly advantageous for elderly and/or frail patients. Nine (75%) of the 12 patients achieved complete response (CR). The other three had significant improvement with greater than 80% clearing of their disease and resolution of symptoms. All six patients with generalized plaque disease achieved complete response and remained free of disease from 2 to 16 months. Two of three node positive patients also achieved complete response; one, with massive biopsy-documented mycosis fungoides nodal disease and deep open tumors, remained relapse-free over 2 years. Only one of the three patients with erythroderma/Sezary syndrome achieved a complete response, which was short lived.

  12. No evidence of HTLV-I infection in patients with mycosis fungoides and Sezary syndrome.

    PubMed

    Pawlaczyk, M; Filas, V; Sobieska, M; Gozdzicka-Józefiak, A; Wiktorowicz, K; Breborowicz, J

    2005-01-01

    The involvement of human T-cell lymphotropic virus type I (HTLV-I) in the etiology of cutaneous T-cell lymphomas (CTCL) is still controversial. The aim of the study was to evaluate the role of HTLV-I in the pathogenesis of mycosis fungoides (MF) and Sezary syndrome (SS) in Polish patients. The studied group consisted of 42 patients with MF, 5 with SS and 25 with chronic dermatitis. DNA was extracted from snap-frozen and paraffin-embedded skin biopsies and from peripheral blood. Polymerase chain reaction (PCR or nested PCR) was carried out for amplification of different regions of HTLV-I genome. Primer sets flanking pX, p 19, U5, tax and pol genes were used in the investigation. The presence of HTLV-I antibody was examined in 46 sera samples with the use of anti-HTLV-I/II EIA test. HTLV-I antibodies were not detected in any collected sera samples. PCR with two primer sets homologous to the pX region of HTLV-I showed negative results in all samples investigated. To confirm these results two other primer pairs specific for U5 and gag regions were designed. With these primer pairs no PCR product, except that in positive control, was observed. For more sensitive amplification a nested-PCR with pol and tax specific primers was performed. HTLV-I probably does not play an important role in the pathogenesis of MF in Polish patients.

  13. Mycosis fungoides two decades after exposure to sulphur mustard: a follow-up of 1100 victims.

    PubMed

    Emadi, S N; Shiri, M; Shiri, Z; Emadi, S E; Mortazavi, H; Nikoo, A; Akhavan-Moghaddam, J

    2017-03-01

    Sulphur mustard (SM) is an alkylating chemical warfare agent which causes acute and chronic injuries to the eyes, skin, lung and respiratory tract. We aimed to investigate the relationship between SM poisoning and Mycosis fungoides (MF) as a late consequence. In this retrospective study, the medical files of 1100 Iranian veterans confirmed to have exposure to SM agent during the Iraq-Iran war of the 1980s were reviewed. All 10 cases with MF were confirmed by clinical and histopathological examinations. The mean age of the studied subjects was 43.3 ± 9.8 (years). In comparison to MF incidence rate in Iranian general population (0.39/100 000 person-years), we found an incidence rate of 0.799/100 000 person-years for MF among those who had short-term exposure to SM. The most common sites for SM lesions were flexural and thin skin areas. The main limitation was the retrospective design. This study indicates that the risk of MF in those exposed to SM may increase over time. Therefore, their follow-up is recommended. © 2016 European Academy of Dermatology and Venereology.

  14. The spectrum of pigmented purpuric dermatosis and mycosis fungoides: atypical T-cell dyscrasia.

    PubMed

    Ladrigan, Manasi Kadam; Poligone, Brian

    2014-12-01

    We report the case of a healthy 17-year-old adolescent boy with an unremarkable medical history who presented with an asymptomatic fixed rash on the abdomen, buttocks, and legs. The rash initially developed in a small area on the right leg 2 years prior and had progressed slowly. Prior biopsies were consistent with pigmented purpura. Clinical examination revealed multiple annular purpuric patches on the abdomen, buttocks, and legs covering approximately 20% of the body surface area without lymphadenopathy or hepatosplenomegaly. Additional biopsies demonstrated changes consistent with mycosis fungoides (MF). T-cell receptor g gene rearrangements demonstrated clonality. The patient was diagnosed with stage IB MF of the pigmented purpura-like variant. The patient responded well to psoralen plus UVA therapy. It has been proposed that pigmented purpuric dermatosis (PPD) is a form of cutaneous T-cell lymphoid dyscrasia and that T-cell gene rearrangement studies should be obtained for prognostic evaluation in patients with widespread disease. In our patient, the clinical appearance of the lesions, pathologic findings, and gene rearrangement studies led to the diagnosis of MF. Until the potential for evolution of PPD to malignant disease is better understood, further evaluation of MF in patients with an unusual presentation of pigmented purpura is warranted.

  15. Increase of DC-LAMP+ mature dendritic cell subsets in dermatopathic lymphadenitis of mycosis fungoides.

    PubMed

    Tada, Kotaro; Hamada, Toshihisa; Asagoe, Kenji; Umemura, Hiroshi; Mizuno-Ikeda, Kazuko; Aoyama, Yumi; Otsuka, Masaki; Yamasaki, Osamu; Iwatsuki, Keiji

    2014-01-01

    Little is known about the immunological milieu of the skin-draining lymph nodes (LNs) in mycosis fungoides (MF). We studied dendritic cell (DC) subsets in the dermatopathic lymphadenitis of MF patients. We immunohistochemically examined DC subsets and their distribution in 16 LN samples from 14 patients with MF (N1 LN, eight patients; N2, four; and N3, four), and we compared them with non-metastatic sentinel LNs from eight patients with melanoma. The number of S-100 protein+ DCs was markedly increased in the LNs from the MF patients and the major component was DC-LAMP+ mature DCs in the outer and paracortex areas, where DC-SIGN+ immature DCs were relatively decreased in proportion. In contrast, DC-SIGN+ cells were relatively increased in proportion compared to DC-LAMP+ cells in the medulla. Although no significant difference was observed in the proportions of CD1a+ or Langerin+ DCs among the N1, N2, and N3 nodes, CD163+ M2-type macrophages were increased in number in the N2 and N3 nodes. Our observations indicate that mature DCs accumulate in the outer and paracortex areas in dermatopathic lymphadenitis and M2-type macrophages might increase in number during disease progression.

  16. [Total cutaneous irradiation with low energy electrons and mycosis fungoides. Technic and dosimetry].

    PubMed

    Monetti, U; Ragona, R; Anglesio, S; Urgesi, A; Fillini, C

    1987-10-01

    Mycosis fungoides initially involves the epidermis and the superficial layers of derma at a depth of about 1 cm. Wide field irradiation with low energy electrons is therefore the treatment of choice in the initial stages of the disease. In our Institute, total skin electron beam irradiation is delivered with Therac 20 linear accelerator: the lowest available energy is 6 MeV. A lucite sheet of 0.6 cm thickness is used to decrease the energy of the beam. We used film dosimetry to evaluate the homogeneity of dose distribution in an Alderson-Rando phantom with different arrangements of the fields and the lucite sheet: 4 and 6 fields techniques have been compared with different positions of the lucite filter, near the phantom and near the collimator. Six fields yield a better dose distribution: homogeneity is within +/- 3.7%, while with four fields it is within +/- 6%. X-rays contamination is less than 2%. "In vivo" dosimetry has been performed using thermoluminescent dosimeters: homogeneity is within +/- 15%.

  17. STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides.

    PubMed

    Fredholm, Simon; Gjerdrum, Lise Mette R; Willerslev-Olsen, Andreas; Petersen, David L; Nielsen, Inger Ø; Kauczok, Claudia-S; Wobser, Marion; Ralfkiaer, Ulrik; Bonefeld, Charlotte M; Wasik, Mariusz A; Krejsgaard, Thorbjørn; Geisler, Carsten; Ralfkiaer, Elisabeth; Gniadecki, Robert; Woetmann, Anders; Odum, Niels

    2014-10-01

    Eosinophil granulocytes have been implicated in anticancer immunity but recent data indicate that eosinophils can also promote cancer. Herein, we studied eosinophils in skin lesions from 43 patients with mycosis fungoides (MF). The presence of eosinophils correlated with disease stage: 78% of patients with advanced disease displayed eosinophil infiltration, whereas this was only seen in 11% of patients with patches (p<0.01), and in 48% of those with plaque disease. Importantly, 72% of patients with positive staining for phospho-signal-transducer-and-activator-of-transcription (pY-STAT3) in malignant T-cells also stained positively for eosinophils, whereas this was only observed in 28% of pY-STAT3-negative patients (p<0.01). Notably, malignant T-cells expressed eosinophilic activation and trafficking factors: High-mobility group BOX-1 protein (HMGB1) and interleukin 5 (IL5). STAT3 siRNA profoundly inhibited IL5 but not HMGB1 expression. In conclusion, these data suggest that malignant T-cells orchestrate accumulation and activation of eosinophils supporting the notion of STAT3 being a putative target for therapy.

  18. Mycosis fungoides and Sezary syndrome are not associated with HTLV-I infection: an international study.

    PubMed

    Bazarbachi, A; Soriano, V; Pawson, R; Vallejo, A; Moudgil, T; Matutes, E; Peries, J; Molina, A; de The, H; Schulz, T F; Catovsky, D; Gill, P S

    1997-09-01

    Association between mycosis fungoides (MF), its leukaemic variant Sezary syndrome (SS) and the human T-cell lymphotropic virus type-I (HTLV-I) has been controversial, with the reported incidence of infection varying between 0% and nearly 100%. We studied 127 patients (85 MF, 28 SS, five Sezary cell leukaemia, four lymphomatoid papulosis, and five unspecified cutaneous T-cell lymphomas (CTCL)) originating from Europe (France, Spain, U.K., Portugal) or from U.S.A. (California) for the presence of HTLV-I infection markers. HTLV-I and -II serology were performed on 78 patients using standard immunological methods. Reverse transcriptase (RT) assay was also performed in 26 cases using an RT-PCR-based method of high sensitivity. Molecular analyses were performed on 215 DNA samples (121 from fresh PBMCs, 26 from PBMCs after short-term culture and 68 from skin lesions) by PCR amplification using HTLV-I and -II gag, pol, env, pX and LTR specific primers. Immunological tests were negative except for two sera which were indeterminate. PCR with all HTLV-I and -II primer pairs showed negative results in all 215 samples investigated. No RT activity was detected in short-term PBMC cultures of any of the 26 cases studied. The results of this large study from five different countries clearly indicate that MF and SS are not associated with HTLV-I infection.

  19. Conjunctival Involvement of T-Cell Lymphoma in a Patient with Mycosis Fungoides.

    PubMed

    Aldrees, Sultan S; Zoroquiain, Pablo; Alghamdi, Sarah A; Logan, Patrick T; Callejo, Sonia; Burnier, Miguel N

    2016-01-01

    Background. Ocular involvement in mycosis fungoides (MF) cases occurs in one-third of patients with the eyelid being the most frequent site affected; however, conjunctival involvement is rarely reported. Herein, we report a rare case of conjunctival involvement of MF. Case Presentation. A 66-year-old man who was previously diagnosed with MF in 2010 and was treated presented in 2014 complaining of foreign body sensation and redness in both eyes. Slit lamp examination of both eyes showed erythematous conjunctival growth that extended circumferentially. Physical examination revealed erythematous skin lesions on different body parts. Conjunctival biopsy was performed and revealed a dense, highly polymorphic lymphocytic population. The immunophenotype demonstrated a neoplastic T-cell origin consistent with MF. A diagnosis of conjunctival involvement by MF was made. The conjunctiva was treated with radiotherapy resulting in tumor regression. There were no recurrences at the 6-month follow-up. Conclusion. T-cell lymphoma should be considered in patients with a history of MF presenting with conjunctival and skin lesions.

  20. Posttranslational Modifications of Transthyretin Are Serum Markers in Patients with Mycosis Fungoides1

    PubMed Central

    Escher, Niko; Kaatz, Martin; Melle, Christian; Hipler, Christina; Ziemer, Mirjana; Driesch, Dominik; Wollina, Uwe; von Eggeling, Ferdinand

    2007-01-01

    Cutaneous T-cell lymphomas (CTCLs) are characterized by the recruitment of malignant T-cell clones, predominantly of the CD4+ T-helper subpopulation, into the skin. Mycosis fungoides (MF) is the most common type of CTCL and accounts for almost 50% of all primary cutaneous lymphomas. The ProteinChip technology surface-enhanced laser desorption/ionization time of flight/mass spectrometry (SELDI-TOF-MS) was used to detect biomarkers in sera from MF patients (n = 25) and healthy controls (n = 26). Therefore, diluted sera were applied to IMAC30 ProteinChip arrays, and the resulting protein profiles were bioinformatically analyzed. A protein set that distinguishes MF patients from healthy controls with a sensitivity of 82.6% and a specificity of 100% was identified. Four significant peaks were identified by two-dimensional gel electrophoresis, immunodepletion, and SELDI-TOF-MS as transthyretin (TTR) and three TTR modifications. A subsequent enzyme-linked immunosorbent assay confirmed these findings. The ability to detect and identify proteins and protein modifications using SELDI-TOF-MS might reveal a better insight on this kind of disease and may lead to a better understanding and earlier detection of MF patients. PMID:17401465

  1. Two cases of aggressive nontumoral folliculotropic mycosis fungoides with visceral involvement.

    PubMed

    Brugière, C; Karanian-Philippe, M; Comoz, F; Dompmartin, A; Galateau-Sallé, F; Verneuil, L

    2014-10-01

    Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma (CTCL), and folliculotropic MF (FMF) is one clinical variant of classic MF. MF generally has a good prognosis with an indolent clinical course, but for FMF greater therapeutic resistance is suggested. Visceral involvement is very rare in these two clinical forms. We report two exceptional cases of FMF with pulmonary and hepatic involvement. Five years after their initial diagnoses, patient 1 presented with a pulmonary localization of his FMF, and patient 2 with liver involvement, without lymph node or T-cell clones in the blood. These two patients had FMF corresponding to stage T2N0M1B0. These two cases highlight the aggressiveness of this rare variant of MF. They suggest that the T lymphocytes found in the folliculotropic form of CTCL could be characterized by greater visceral tropism. They raise the question of the molecular and functional characteristics of these T lymphocytes, and the possibility of a common target in the hair follicles and certain organs. Studies have shown that chemokine receptors are likely to be involved in the skin tropism that characterizes CTCL. These two cases show the aggressiveness of FMF and point to the interest in comparing the molecular characteristics of T lymphocytes in the folliculotropic and nonfolliculotropic forms of CTCL.

  2. Pityriasis Lichenoides-like Mycosis Fungoides: Clinical and Histologic Features and Response to Phototherapy

    PubMed Central

    Jang, Min Soo; Kang, Dong Young; Park, Jong Bin; Kim, Joon Hee; Park, Kwi Ae; Rim, Hark

    2016-01-01

    Background Pityriasis lichenoides (PL)-like skin lesions rarely appear as a specific manifestation of mycosis fungoides (MF). Objective We investigated the clinicopathological features, immunophenotypes, and treatments of PL-like MF. Methods This study included 15 patients with PL-like lesions selected from a population of 316 patients diagnosed with MF at one institution. Results The patients were between 4 and 59 years of age. Four patients were older than 20 years of age. All of the patients had early-stage MF. In all patients, the atypical lymphocytic infiltrate had a perivascular distribution with epidermotropism. The CD4/CD8 ratio was <1 in 12 patients. Thirteen patients were treated with either narrowband ultraviolet B (NBUVB) or psoralen+ultraviolet A (PUVA), and all of them had complete responses. Conclusion PL-like MF appears to have a favorable prognosis and occurrence of this variant in adults is uncommon. MF should be suspected in the case of a PL-like skin eruption. Therefore, biopsy is required to confirm the diagnosis of PL-like MF, and NBUVB is a clinically effective treatment. PMID:27746631

  3. Expression of PTEN in mycosis fungoides and correlation with loss of heterozygosity.

    PubMed

    Katona, Terrence M; Smoller, Bruce R; Webb, Alden L; Hattab, Eyas M; Khalil, Ahmed; Hiatt, Kim M

    2013-07-01

    Mycosis fungoides (MF) exhibits a variety of underlying molecular defects including aberrations involving the PTEN tumor suppressor gene. Specifically, loss of heterozygosity of PTEN has been previously demonstrated. We hypothesize that abnormalities of PTEN may result in altered immunohistochemical expression of its protein product. Thirty-six MF specimens were stained with monoclonal antibody against PTEN protein. The percentage of nuclei retaining PTEN expression and the staining intensity was recorded. Average percentage of lymphoma cells retaining expression of the PTEN protein was 92% within patch-stage lesions, 81.4% in plaque-stage lesions, and 81.1% in tumor-stage lesions. Average intensity of staining for patch-stage lesions was 2.90, 2.50 for plaque lesions and 2.44 for tumor lesions. Cases lacking loss of heterozygozity at PTEN (n = 6) had an average expression of 81% and an average intensity of staining of 2.42. Whereas, cases with loss of heterozygozity at PTEN (n = 6) had an average expression of 75% of cells with an average staining intensity of 2.33. The percentage of cells retaining PTEN and staining intensity decrease from patch- to plaque-stage lesions, whereas both parameters show mild diminution in tumor lesions compared with plaque lesions. PTEN expression in a small sample seems to correlate with previous demonstration of loss of heterozygosity at the molecular level. Although a trend for loss of PTEN expression exists with histologic progression of MF, the effect is modest and may not represent the pivotal defect in MF pathogenesis.

  4. New insights into folliculotropic mycosis fungoides (FMF): A single-center experience.

    PubMed

    Hodak, Emmilia; Amitay-Laish, Iris; Atzmony, Lihi; Prag-Naveh, Hadas; Yanichkin, Natalia; Barzilai, Aviv; Kershenovich, Ruben; Feinmesser, Meora

    2016-08-01

    It is generally accepted that folliculotropic mycosis fungoides (FMF) is usually typified by indurated plaques and tumors mainly on the head/neck and an aggressive course. However, its clinical manifestations have long been recognized to be quite variable, and some studies indicate a better prognosis for certain presentations. We sought to summarize our experience with the clinicopathological presentations of FMF and impact on prognosis. Data were collected retrospectively for adults with FMF followed up prospectively at a tertiary medical center in 1995 through 2014. In all, 34 patients presented with follicle-based patch/flat plaques, keratosis pilaris-like lesions, and/or acneiform lesions, defined clinically as early stage (IA, IB), and 15 presented with follicle-based infiltrated plaques and/or tumors, defined as advanced stage (IIB). The head/neck was involved in all tumor-stage cases, whereas early-stage lesions involved mainly the trunk/limbs. The tumor stage was characterized by more pruritus, heavier perifollicular infiltrates, greater vertical depth, and more frequent presence of eosinophils. On multivariate analysis, infiltrate density was the only significant histopathological discriminator between the stages. Estimated 5-year survival was 0.94 in the early-stage group and 0.69 in the tumor-stage group. Lack of long-term follow-up and relatively small sample are limitations. FMF presents with 2 distinct patterns of clinicopathologic features, early stage and advanced stage, each with different prognostic implications. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  5. Rapidly progressive stage IVB mycosis fungoides treated with low-dose total skin electron beam therapy.

    PubMed

    Chowdhary, Mudit; Kabbani, Ahmad A; Rimtepathip, Parin; Cole, David A; Cohen, David J

    2015-01-01

    Mycosis fungoides (MF) is the most common subtype of primary cutaneous T-cell lymphoma. Normally, MF has an indolent course although patients can progress to an advanced disease state (stages IIB-IVB). Advanced-stage disease is typically aggressive, leaving patients with debilitating symptoms and a decreased quality of life. Moreover, advanced-stage MF often proves refractory to therapy and carries a very poor prognosis. Total skin electron beam (TSEB) therapy is a well-established and successful treatment for early stage MF; however, its efficacy dramatically decreases with advanced-stage disease. In fact, TSEB in advanced-stage MF is generally considered to be palliative. Current consensus guidelines recommend a dose of 30-36 Gy to be delivered in 8-10 weeks; however, limited studies exist to determine the ideal treatment in Stage IV MF. Herein, we describe a case of a 50-year-old male who developed rapidly progressive stage IVB (T3N3M1B0) MF and was treated with low-dose (24 Gy) TSEB over 8 weeks. The patient was not treated with any systemic therapy before starting TSEB due to the widespread nature and the speed of disease progression. Remarkably, our patient showed nearly complete (95%) response of his MF with no apparent side effects from radiation. Furthermore, he has remained in remission over 4 years, requiring only a small boost to a few "shadowed" areas. Our case illustrates the benefit of using TSEB in stage IV MF. Additionally, our experience shows that low-dose TSEB can occasionally be efficacious in stage IV disease.

  6. Revisiting Low-Dose Total Skin Electron Beam Therapy in Mycosis Fungoides

    SciTech Connect

    Harrison, Cameron; Young, James; Navi, Daniel; Riaz, Nadeem; Lingala, Bharathi; Kim, Youn; Hoppe, Richard

    2011-11-15

    Purpose: Total skin electron beam therapy (TSEBT) is a highly effective treatment for mycosis fungoides (MF). The standard course consists of 30 to 36 Gy delivered over an 8- to 10-week period. This regimen is time intensive and associated with significant treatment-related toxicities including erythema, desquamation, anhydrosis, alopecia, and xerosis. The aim of this study was to identify a lower dose alternative while retaining a favorable efficacy profile. Methods and Materials: One hundred two MF patients were identified who had been treated with an initial course of low-dose TSEBT (5-<30 Gy) between 1958 and 1995. Patients had a T stage classification of T2 (generalized patch/plaque, n = 51), T3 (tumor, n = 29), and T4 (erythrodermic, n = 22). Those with extracutaneous disease were excluded. Results: Overall response (OR) rates (>50% improvement) were 90% among patients with T2 to T4 disease receiving 5 to <10 Gy (n = 19). In comparison, OR rates between the 10 to <20 Gy and 20 to <30 Gy subgroups were 98% and 97%, respectively. There was no significant difference in median progression free survival (PFS) in T2 and T3 patients when stratified by dose group, and PFS in each was comparable to that of the standard dose. Conclusions: OR rates associated with low-dose TSEBT in the ranges of 10 to <20 Gy and 20 to <30 Gy are comparable to that of the standard dose ({>=} 30 Gy). Efficacy measures including OS, PFS, and RFS are also favorable. Given that the efficacy profile is similar between 10 and <20 Gy and 20 and <30 Gy, the utility of TSEBT within the lower dose range of 10 to <20 Gy merits further investigation, especially in the context of combined modality treatment.

  7. Canine cutaneous epitheliotropic lymphoma (mycosis fungoides) is a proliferative disorder of CD8+ T cells.

    PubMed Central

    Moore, P. F.; Olivry, T.; Naydan, D.

    1994-01-01

    Canine epitheliotropic lymphoma (mycosis fungoides [MF]) is a spontaneous neoplasm of skin and mucous membranes that occurs in old dogs (mean age 11 years) and has no breed predilection. The lesions evolve from a patch-plaque stage with prominent epitheliotropism into a tumor stage in which distant metastasis is observed. Unlike human MF, epitheliotropism of the lymphoid infiltrate is still prominent in tumor stage lesions. Tropism of the lymphoid infiltrate for adnexal structures, especially hair follicles and apocrine sweat glands, was marked in all clinical stages of canine MF. Twenty-three cases of MF were subjected to extensive immunophenotypic analysis in which reagents specific for canine leukocyte antigens and fresh frozen tissue sections of the canine lesions were used. Canine MF proved to be a T cell lymphoma in which the epitheliotropic lymphocytes consistently expressed CD3 (22 cases) and CD8 (19 cases); CD3+CD4-CD8- lymphocytes predominated in the remaining 4 cases. In this regard, canine MF clearly differed from human MF in which a CD4 immunophenotype predominates in the T cell infiltrate. Lack of expression of CD45RA by epitheliotropic T cells and intense expression of a beta 1 integrin (VLA-4-like) suggested that T cells in canine MF belonged to the memory subpopulation, as has been suggested for T cells in human MF. Pan-T cell antigen loss or discordant expression also proved useful as phenotypic indicators of neoplasia in canine MF. Loss of CD5 was observed in epitheliotropic T cells in 63% of cases. Discordance of neoplastic T cell Thy-1 expression was frequently observed between epithelial and dermal or submucosal compartments. We conclude that canine MF still represents a useful spontaneous animal disease model of human cutaneous T cell lymphoma, despite the immunophenotypic differences, which may reflect operational differences between human and canine skin-associated lymphoid tissue. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure

  8. The difficulty of detecting HTLV-1 proviral sequences in patients with mycosis fungoides.

    PubMed

    Pancake, B A; Zucker-Franklin, D

    1996-12-01

    Although most patients with cutaneous T cell lymphomas, including mycosis fungoides (MF) and its leukemic variant, the Sézary syndrome, are seronegative for antibodies to the human T cell lymphotropic viruses (HTLV-I/II), it has recently been shown that > 95% of such patients harbor proviral DNA sequences related to the region of the HTLV genome that encodes the transregulatory/transforming gene, tax. However, the demonstration of HTLV sequences, even after amplification by polymerase chain reaction (PCR), has not been universally successful, and some investigators continue to question this observation. In an effort to resolve this controversy, we have compared published methodologies that have been less successful with techniques currently used in this laboratory. Major differences were found in (a) the nature of the cells used [freshly isolated versus cultured peripheral blood mononuclear cells (PBMC)] and (b) the methods used to prepare samples for PCR (whole cell lysates versus DNA extracts). PBMC from 10 different MF patients and the healthy daughter of 1 of the patients were subjected to comparative analyses. While all of the PBMC lysates were positive, the DNA extract from only one of these individuals revealed HTLV tax sequences. Studies were also conducted comparing cell lysates and DNA extracts of cultured cells derived from tax sequence-positive PBMC from seven different MF patients. The cells from four of the seven were shown to have retained tax sequences after varying times in culture, when whole-cell lysates were used as targets for PCR amplification and Southern analysis, whereas none of the DNA extracts were positive. It appears that the use of whole-cell lysates instead of DNA extracts and the use of fresh instead of cultured cells greatly enhance the ability to detect HTLV-1 tax sequences in specimens from MF patients.

  9. Expression of CXCR4 and CXCL12 and their correlations to the cell proliferation and angiogenesis in mycosis fungoides

    PubMed Central

    Maj, Joanna; Hałoń, Agnieszka; Woźniak, Zbigniew; Plomer-Niezgoda, Ewa; Reich, Adam

    2015-01-01

    Introduction Chemokines play an important role in tumor growth, invasion and metastasis. The CXCR4/CXCL12 axis has been implicated in development of both solid tumors and hematological malignancies and is also relevant in the pathogenesis of the most common primary cutaneous T-cell lymphoma, mycosis fungoides (MF). Aim To evaluate the expression of CXCR4 and CXCL12 in MF and to examine their associations with cell proliferation and angiogenesis. Material and methods The material for the study consisted of skin samples obtained from 56 patients with MF and 20 healthy volunteers. The expression of CXCR4 and CXCL12 was assessed by immunohistochemistry on the paraffin blocks and compared to the expression of angiogenesis marker (CD34) and proliferation indicators (Ki-67, AgNORs). Results The expression of chemokine CXCL12 and its receptor CXCR4 was significantly higher in MF than in the healthy skin (p < 0.001). There was no significant difference between early and advanced stages of MF. Similarly, there was no statistically important correlation between the expression of CXCR4/CXCL12 and angiogenesis and proliferation markers, however a significant correlation between CD34 and AgNORs expression was found (p < 0.001). Conclusions The CXCR4/CXCL12 axis seems to play an important role in MF development in the early as well as in the advanced stages of the disease. Therefore, the CXCR4/CXCL12 axis seems to be an interesting potential target for the future strategies of new drug development, giving hope for more efficacious therapies for mycosis fungoides. PMID:26755907

  10. Mycosis fungoides: HLA class II associations among Ashkenazi and non-Ashkenazi Jewish patients.

    PubMed

    Hodak, E; Lapidoth, M; Kohn, K; David, D; Brautbar, B; Kfir, K; Narinski, N; Safirman, S; Maron, M; Klein, K

    2001-12-01

    An immunogenetic mechanism has been suggested to play a role in the pathogenesis of mycosis fungoides (MF). While results of studies on HLA class I associations haveproved inconsistent, two previous studies showed that certain HLA class II alleles were significantly increased among North American caucasian patients with MF: HLA-DRB1*11 and DQB1*03. To investigate the possible HLA class I and class II associations with MF among Jewish patients. The patient group comprised 68 Jewish patients with MF: 38 Ashkenazi and 30 non-Ashkenazi. The control group comprised 252 healthy Jewish volunteers: 132 Ashkenazi and 120 non-Ashkenazi. Tissue typing for HLA class I (A and B) was performed using the National Institutes of Health microlymphocytotoxicity technique. DNA-based low-medium resolution analysis for DRB1* and DQB1* alleles was performed using polymerase chain reaction (PCR) amplification with sequence-specific primers. For those alleles found to have significantly increased frequency, high-resolution analysis was done by means of PCR sequence-specific oligotyping. The allele frequency of HLA-DRB1*11 was found to be significantly increased but only among Ashkenazi patients with MF (30% vs. 19% in the controls; P = 0.034). High-resolution analysis for DRB1*11, not previously performed, suggested that its greater frequency is due to the increased number of Ashkenazi MF patients with the DRB1*1104 allele (P corrected = 0.036). Analysed together, DQB1*03 alleles (DQB1*0301-0304) had a significantly greater frequency in MF as a group as compared with controls (47% vs. 33%, P = 0.003). DQB1*0301 was demonstrated to be the specific allele associated with MF in Jewish patients (allele frequency of 36% vs. 23% in controls; P corrected = 0.0068), which was not the case for North American caucasian patients with MF. No greater frequencies of any of the HLA class I A or B antigens were found. Our findings further demonstrate the 'universality' of MF HLA class II susceptibility

  11. Expression of SATB1, MTI/II and Ki-67 in Mycosis Fungoides.

    PubMed

    Jankowska-Konsur, Alina; Kobierzycki, Christopher; Reich, Adam; Grzegrzolka, Jedrzej; Bieniek, Andrzej; Dziegiel, Piotr

    2016-01-01

    A genome organizer protein, special AT-rich sequence binding protein 1, (SATB1), was recently shown to play an important role in the development and spread of various malignancies. Metallothioneins I and II (MTI/II) are multifunctional proteins involved, among others, in cell proliferation and apoptosis resistance in tumors. The role and relevance of these factors in mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is not fully understood. The aim of the present analysis was to evaluate the expression and potential correlation of SATB1, MTI/II and Ki-67 with clinicopathological data in MF. We performed immunohistochemical analysis for SATB1, MTI/II and Ki-67 on 90 cases of MF and 19 controls (chronic benign dermatoses). The expression of SATB1 and Ki-67 was analyzed in cancer cell nuclei, whereas nuclear and cytoplasmic expressions of MTI/II were scored separately (nMT, cMT; respectively). We recorded a significantly higher expression of SATB1 and cMT in MF compared to the control group (p<0.002, p=0.04, respectively, Student's t-test). We also noted significant differences in the mean (±SD) expression of nMT and cMT in advanced MF compared to early MF, (1.4±1.3 vs. 0.9±0.9, 4.1±3.8 vs. 2.5±2.9, respectively; p=0.04 for both). Similarly, Ki-67 expression was significantly higher in advanced MF (p<0.01). The expression of SATB1, cMT and Ki-67 was significantly higher in more infiltrating skin lesions (p<0.001, p=0.08 and p<0.001, respectively). Regarding extracutaneous involvement, a higher expression of SATB1, nMT, cMT and Ki-67 was found in patients with clinical or histological involvement of lymph nodes (N1-3 vs. N0) (p<0.001, p=0.002, p<0.001 and p=0.1, respectively). A marked correlation was observed between SATB1 and Ki-67 (Spearman correlation test: r=0.53, p<0.001). No associations between SATB1, nMT and cMT expression and demographic data nor overall survival were found. Our study provides data on the differences in the

  12. Annular lichenoid dermatitis of youth: a separate entity or on the spectrum of mycosis fungoides? Case report and review of the literature.

    PubMed

    Kazlouskaya, Viktoryia; Trager, Jonathan D K; Junkins-Hopkins, Jacqueline M

    2015-06-01

    Annular lichenoid dermatitis (ALDY) is a rare dermatosis that is most often seen in children and young adults and is characterized by annular patches with raised borders, most frequently on the trunk and the groin. A distinct lichenoid tissue reaction involving the base of the rete, resulting in squared-off rete ridges, helps to differentiate this from other lichenoid dermatoses and mycosis fungoides (MF). Herein, we report an additional case of this condition in a 7-year-boy, whose biopsy exhibited the typical quadrangular rete alteration and also contained distinct aggregates of CD8+ lymphocytes, Langerhans cells and colloid bodies within the involved rete. A literature review with emphasis on the clinical and histopathological differential diagnosis reveals additional clinical features of ALDY to potentially help differentiate this entity from annular presentations of mycosis fungoides.

  13. Cell-bound IgE and increased expression of Fc epsilon-receptors on dendritic cells in cutaneous infiltrates of mycosis fungoides.

    PubMed Central

    Preesman, A H; Van de Winkel, J G; Magnusson, C G; Toonstra, J; van der Putte, S C; van Vloten, W A

    1991-01-01

    Skin biopsies of 31 non-atopic patients, 20 with mycosis fungoides, six with psoriasis and five with contact dermatitis, and of five non-atopic healthy controls were compared for the presence of cell-bound IgE and vacant IgE binding sites. IgE+ cells were demonstrated in the cutaneous infiltrate of nine (45%) patients with mycosis fungoides, two (33%) with psoriasis and one (20%) with contact dermatitis. Following pre-incubation of skin sections with IgE myeloma protein to saturate vacant IgE-binding sites, 14 out of 16 patients (88%) with stage I mycosis fungoides, five (83%) patients with psoriasis and one (20%) with contact dermatitis showed an increase in the number of IgE+ cells. While cell-bound IgE was positively related to serum IgE levels the expression of IgE-binding sites was not. All IgE+ cells were HLA-DR+ dendritic cells identified as either macrophages (CD68+, CD14+) or Langerhans cells (CD1+). Skin biopsies of non-atopic healthy controls or clinically uninvolved skin in mycosis fungoides had neither any IgE+ cells nor any vacant binding sites. Inhibition studies with IgG1, IgG4 and IgE myeloma proteins as well as with several enzymatic fragments of IgE demonstrated that IgE interacted with Fc epsilon-receptors through isotype-specific structures on the Fc epsilon-fragment. Four anti-CD23 monoclonal antibodies, however, were unable to stain vacant Fc epsilon-receptors nor could they block IgE-binding. We hypothesize that locally-secreted lymphokines, like IL-4 or interferon-gamma, induce Fc epsilon-receptors on dendritic cells in the cutaneous infiltrate and that these receptors become occupied in parallel with elevated serum IgE levels. Images Fig. 1 Fig. 2 PMID:1834378

  14. Lichen striatus with syringotropism and hyperplasia of eccrine gland cells: a rare phenomenon that should not be confused with syringotropic mycosis fungoides.

    PubMed

    Wang, Lei; Chen, Fengming; Liu, Yu; Gao, Tianwen; Wang, Gang

    2016-11-01

    Syringotropism is characterized by lymphocyte infiltration in the eccrine gland and is usually associated with various degrees of hyperplasia of eccrine gland cells. This phenomenon has been reported in rare cases of mycosis fungoides, which are also called as syringotropic mycosis fungoides. We studied seven cases of lichen striatus associated with syringotropism and hyperplasia of eccrine gland cells, diagnosed at our dermatology department in the past 5 years. The hematoxylin and eosin-stained slides from these cases were analyzed, and immunohistochemical and T-cell receptor gene rearrangement studies were performed. Of the seven cases, two showed prominent and five showed subtle syringotropism and hyperplasia of eccrine gland cells. Immunohistochemical study showed mixed infiltration by T-cells and B-cells around the eccrine glands. The T-cells were composed of CD4 and CD8-positive cells. T-cell receptor gene rearrangement study showed negative results in all the cases. Syringotropism and hyperplasia of eccrine gland cells is a rare phenomenon in lichen striatus. Dermatopathologists should be aware of this to avoid misdiagnosis as syringotropic mycosis fungoides. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides

    SciTech Connect

    Kaye, F.J.; Bunn, P.A. Jr.; Steinberg, S.M.; Stocker, J.L.; Ihde, D.C.; Fischmann, A.B.; Glatstein, E.J.; Schechter, G.P.; Phelps, R.M.; Foss, F.M.; )

    1989-12-28

    Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonradomized studies have suggested that early aggressive therapy may improve the prognosis in this usually fatal disease. We studied 103 patients with mycosis fungoides, who, after complete staging, were randomly assigned to receive either combination therapy, consisting of 3000 cGy of electron-beam radiation to the skin combined with parenteral chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine (n = 52) or sequential topical treatment (n = 51). The prognostic factors were well balanced in the two groups. Combined therapy produced considerable toxicity: 12 patients required hospitalization for fever and transient neutropenia, 5 had congestive heart failure, and 2 were later found to have acute nonlymphocytic leukemia. Patients receiving combined therapy had a significantly higher rate of complete response, documented by biopsy, than patients receiving conservative therapy (38 percent vs. 18 percent; P = 0.032). After a median follow-up of 75 months, however, there was no significant difference between the treatment groups in disease-free or overall survival. We conclude that early aggressive therapy with radiation and chemotherapy does not improve the prognosis for patients with mycosis fungoides as compared with conservative treatment beginning with sequential topical therapies.

  16. CCR4+T cell recruitment to the skin in mycosis fungoides: potential contributions by thymic stromal lymphopoietin and interleukin-16.

    PubMed

    Tuzova, Marina; Richmond, Jillian; Wolpowitz, Deon; Curiel-Lewandrowski, Clara; Chaney, Keri; Kupper, Thomas; Cruikshank, William

    2015-02-01

    Mycosis fungoides (MF) is characterized by skin accumulation of CCR4+CCR7- effector memory T cells; however the mechanism for their recruitment is not clearly identified. Thymic Stromal Lymphopoietin (TSLP) is a keratinocyte-derived cytokine that triggers Th2 immunity and is associated with T cell recruitment to the skin in atopic dermatitis. Interleukin-16 (IL-16) is a chemoattractant and growth factor for CD4+T cells. We hypothesized that TSLP and IL-16 could contribute to recruitment of malignant T cells in MF. We found elevated TSLP and IL-16 in very early stage patients' plasma and skin biopsies, prior to elevation in CCL22. Both TSLP and IL-16 induced migratory responses of CCR4+TSLPR+CD4+CCR7-CD31+cells, characteristic of malignant T cells in the skin. Co-stimulation also resulted in significant proliferative responses. We conclude that TSLP and IL-16, expressed at early stages of disease, function to recruit malignant T cells to the skin and contribute to their enhanced proliferation.

  17. Evolving Insights in the Pathogenesis and Therapy of Cutaneous T-cell lymphoma (Mycosis Fungoides and Sezary Syndrome)

    PubMed Central

    Wong, Henry K.; Mishra, Anjali; Hake, Timothy; Porcu, Pierluigi

    2015-01-01

    Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of malignancies derived from skin-homing T cells. The most common forms of CTCL are Mycosis Fungoides (MF) and Sezary Syndrome (SS). Accurate diagnosis remains a challenge due to the heterogeneity of presentation and the lack of highly characteristic immunophenotypical and genetic markers. Over the past decade molecular studies have improved our understanding of the biology of CTCL. The identification of gene expression differences between normal and malignant T-cells has led to promising new diagnostic and prognostic biomarkers that now need validation to be incorporated into clinical practice. These biomarkers may also provide insight into the mechanism of development of CTCL. Additionally, treatment options have expanded with the approval of new agents, such as histone deacetylase inhibitors. A better understanding of the cell biology, immunology and genetics underlying the development and progression of CTCL will allow the design of more rational treatment strategies for these malignancies. This review summarizes the clinical epidemiology, staging and natural history of MF and SS; discusses the immunopathogenesis of MF and the functional role of the malignant T-cells; and reviews the latest advances in MF and SS treatment. PMID:21883142

  18. A case of IgA nephropathy associated with mycosis fungoides that developed into rapidly progressive glomerulonephritis.

    PubMed

    Hara, Masaki; Nemoto, Tetsuo; Hijima, Tsunekazu; Tsuchiya, Ken; Nitta, Kosaku; Ando, Minoru

    2013-02-01

    A 53-year-old Japanese male was diagnosed with atopic dermatitis and initiated treatment with a local dermatologist in February 2001. A routine medical check-up revealed proteinuria, microscopic hematuria and slight elevation of serum creatinine level in spring 2006. He was referred to our hospital for nephrology consultation and followup.In December 2009, he developed a sudden high fever of greater than 39 °C with sore throat. In addition, his serum creatinine level greatly increased to 4.6 mg/dl. His prevalent renal illness was thought to be rapidly progressive glomerulonephritis (RPGN). Soon after admission, kidney and skin biopsies were performed. The kidney specimens showed that the glomeruli had proliferative mesangial cells strongly positive for anti-IgA antibody, 75% of which manifested fibrocellular crescentic formation surrounding the Bowman's capsules. His skin disease was pathologically proven to be mycosis fungoides(MF). It is likely that his kidney disease was exacerbated by the upper respiratory tract infection and converted to RPGN. Ash is kidney function rapidly declined, hemodialysis therapy was initiated and he remains on chronic dialysis therapy. This is a serious case of IgA nephropathy associated with MF,which developed into RPGN and subsequent end-stage renal disease.

  19. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions.

    PubMed

    Jawed, Sarah I; Myskowski, Patricia L; Horwitz, Steven; Moskowitz, Alison; Querfeld, Christiane

    2014-02-01

    Both mycosis fungoides (MF) and Sézary syndrome (SS) have a chronic, relapsing course, with patients frequently undergoing multiple, consecutive therapies. Treatment is aimed at the clearance of skin disease, the minimization of recurrence, the prevention of disease progression, and the preservation of quality of life. Other important considerations are symptom severity, including pruritus and patient age/comorbidities. In general, for limited patch and plaque disease, patients have excellent prognosis on ≥1 topical formulations, including topical corticosteroids and nitrogen mustard, with widespread patch/plaque disease often requiring phototherapy. In refractory early stage MF, transformed MF, and folliculotropic MF, a combination of skin-directed therapy plus low-dose immunomodulators (eg, interferon or bexarotene) may be effective. Patients with advanced and erythrodermic MF/SS can have profound immunosuppression, with treatments targeting tumor cells aimed for immune reconstitution. Biologic agents or targeted therapies either alone or in combination--including immunomodulators and histone-deacetylase inhibitors--are tried first, with more immunosuppressive therapies, such as alemtuzumab or chemotherapy, being generally reserved for refractory or rapidly progressive disease or extensive lymph node and metastatic involvement. Recently, an increased understanding of the pathogenesis of MF and SS with identification of important molecular markers has led to the development of new targeted therapies that are currently being explored in clinical trials in advanced MF and SS.

  20. Composite lymphoma of mycosis fungoides and cutaneous small B-cell lymphoma in a 73-year-old male patient.

    PubMed

    Whitling, Nicholas A; Shanesmith, Rebecca P; Jacob, Leah; McBurney, Elizabeth; Sebastian, Siby; Wang, Endi; Wang, Alun R

    2013-04-01

    Composite lymphoma of T-cell and B-cell type is uncommon, and the one occurring primarily on skin is extremely rare. Herein, we report a unique case of composite lymphoma of mycosis fungoides and cutaneous small B-cell lymphoma in a 73-year-old male patient. The patient presented with multiple erythematous patches, plaques, and nodules on the upper arms, scalp, and trunk. Four punch biopsies of arm and scalp lesions demonstrated lymphoid infiltrate in superficial to deep dermis with a characteristic zone distribution of T-cell and B-cell components. T cells were distributed in papillary and perifollicular dermis and displayed a larger size with convoluted nuclei, whereas B cells were small sized, assuming nodular infiltrate in mid-deep dermis with coexpression of CD5. Molecular test detected clonal rearrangement of both TCRG and IGH/K genes with identical amplicons for each gene in all 4 biopsies. Clinical staging revealed no extracutaneous lesions. A multidisplinary approach is emphasized to establish a definitive diagnosis.

  1. Characterization of unconventional electron fields for the treatment of mycosis fungoides using the total skin irradiation technique

    NASA Astrophysics Data System (ADS)

    Pagnan González, M. A.; Hernández Oviedo, J. O.; Mitsoura, E.; Ruesga Vázquez, D. R.

    2014-11-01

    Mycosis fungoides is a cutaneous lymphoma that accounts for 2-3% of all lymphomas. Several clinical studies have demonstrated the effectiveness of TSEBT (Total Skin Electron Beam Therapy) in patients with mycosis fungoides. It is important to develop this technique and make it available to a larger number of patients in Mexico. Because large fields for electron TSEBT are required in order to cover the entire body of the patient, beam characterization at conventional treatment distances is not sufficient and a calibration distance of 500cm or higher is required. Materials and methods: Calibration of radiochromic Gafchromic® EBT2 film (RCF) for electrons was performed in a solid water phantom (Scanditronix Wellhöfer) at a depth of 1.4cm and a Source Axis Distance (SAD) of 100cm. A polynomial fit was applied to the calibration curve, in order to obtain the equation relating dose response with optical density. The spatial distribution is obtained in terms of percentage of the dose, placing 3×3cm samples of RCF on the acrylic screen, which is placed in front of the patient in order to obtain maximum absorbed dose on the skin, covering an area of 200×100cm2. The Percentage Depth Dose (PDD) curve was obtained placing RCF samples at depths of 0, 1, 1.2, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8 and 9cm in the solid water phantom, irradiated with an ELEKTA SINERGY Linear Accelerator electron beam, with an energy of 6 MeV, at a Source Skin Distance (SSD) of 500cm, with 1000MU = 100Gy, with a cone of 40×40cm and gantry angle of 90°. The RCFs were scanned on a flatbed scanner (EPSON EXPRESSION 10000 XL) and the images were processed with the ImageJ program using a region of interest (ROI) of 1×1cm2. Results: The relative spatial dose distribution and the percentage depth dose for a SSD of 500±0.5cm, over an area of 200×100cm2 was obtained, resulting to an effective maximum dose depth (Zref) for electrons of 1.4±0.05cm. Using the same experimental data, horizontal and vertical

  2. Characterization of unconventional electron fields for the treatment of mycosis fungoides using the total skin irradiation technique

    SciTech Connect

    González, M. A. Pagnan Mitsoura, E.; Oviedo, J.O. Hernández; Vázquez, D. R. Ruesga

    2014-11-07

    Mycosis fungoides is a cutaneous lymphoma that accounts for 2–3% of all lymphomas. Several clinical studies have demonstrated the effectiveness of TSEBT (Total Skin Electron Beam Therapy) in patients with mycosis fungoides. It is important to develop this technique and make it available to a larger number of patients in Mexico. Because large fields for electron TSEBT are required in order to cover the entire body of the patient, beam characterization at conventional treatment distances is not sufficient and a calibration distance of 500cm or higher is required. Materials and methods: Calibration of radiochromic Gafchromic® EBT2 film (RCF) for electrons was performed in a solid water phantom (Scanditronix Wellhöfer) at a depth of 1.4cm and a Source Axis Distance (SAD) of 100cm. A polynomial fit was applied to the calibration curve, in order to obtain the equation relating dose response with optical density. The spatial distribution is obtained in terms of percentage of the dose, placing 3×3cm samples of RCF on the acrylic screen, which is placed in front of the patient in order to obtain maximum absorbed dose on the skin, covering an area of 200×100cm{sup 2}. The Percentage Depth Dose (PDD) curve was obtained placing RCF samples at depths of 0, 1, 1.2, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8 and 9cm in the solid water phantom, irradiated with an ELEKTA SINERGY Linear Accelerator electron beam, with an energy of 6 MeV, at a Source Skin Distance (SSD) of 500cm, with 1000MU = 100Gy, with a cone of 40×40cm and gantry angle of 90°. The RCFs were scanned on a flatbed scanner (EPSON EXPRESSION 10000 XL) and the images were processed with the ImageJ program using a region of interest (ROI) of 1×1cm{sup 2}. Results: The relative spatial dose distribution and the percentage depth dose for a SSD of 500±0.5cm, over an area of 200×100cm{sup 2} was obtained, resulting to an effective maximum dose depth (Z{sub ref}) for electrons of 1.4±0.05cm. Using the same experimental data

  3. Vernachlässigte klinische Merkmale der follikulotropen Mycosis fungoides: eine große klinische Fallserie.

    PubMed

    Baykal, Can; Atci, Tugba; Ozturk Sari, Sule; Polat Ekinci, Algun; Buyukbabani, Nesimi

    2017-03-01

    Als seltene Form der Mycosis fungoides (MF), ist die follikulotrope MF (FMF) durch ein breites Spektrum klinischer Symptome gekennzeichnet. Dazu gehören, neben den vorherrschenden follikulären Läsionen, auch viele atypische Manifestationen. Das Ziel der vorliegenden Studie war eine klinische Bewertung von FMF-Patienten, unter besonderer Berücksichtigung von vernachlässigten dermatologischen Merkmalen. Insgesamt wurden 27 FMF-Patienten aus dem 572 Patienten umfassenden MF-Register unserer Abteilung retrospektiv bezüglich ihrer Demographie sowie der klinischen Merkmale, Behandlungsformen, Nachsorge und Therapieergebnisse bewertet. Neben den bekannten klinischen Symptomen der FMF fanden wir Lichen-spinulosus-artige Läsionen mit begleitender Hypopigmentierung (n = 3) und Alopezie (n = 2), infiltrierte/erhabene, erythematöse Plaques im Gesicht, die zunächst als Lupus tumidus angesehen wurden (n = 2), pseudotumorale Läsionen, die klinisch eine MF im Tumorstadium vortäuschten (n = 1), dauerhafte Exkoriationen (n = 1), erythematöse, Rosazea-artige Papeln im Gesicht (n = 1) sowie kuppelförmige, asymptomatische, mit Muzin gefüllte (in der Histologie) Papeln/Knoten (n = 2), die andere krankheitsbedingte Läsionen überlagerten. Es kamen mehrere Therapieansätze mit unterschiedlichem Ergebnis zur Anwendung. Acht (29,6 %) Patienten hatten FMF im Spätstadium. Das Bewusstsein für vernachlässigte klinische Symptome kann wesentlich dazu beitragen, verspätete Diagnosen dieser aggressiven MF-Variante zu verringern. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  4. Incidence of Kaposi's sarcoma and mycosis fungoides in the United States including Puerto Rico, 1973-81.

    PubMed

    Biggar, R J; Horm, J; Fraumeni, J F; Greene, M H; Goedert, J J

    1984-07-01

    The incidence of Kaposi's sarcoma (KS) was examined with the use of data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. KS is a manifestation of the recent epidemic of acquired immunodeficiency syndrome (AIDS) that has occurred particularly among homosexual men. The incidence of KS in 1973-79 was found to be higher (0.29 male and 0.07 female cases/100,000/yr) than is usually cited for the pre-AIDS KS incidence rates. Collectively, the 9 SEER registries in the United States showed only a slight increase in the incidence of KS between 1973-79 and 1980-81. However, the SEER registry covering San Francisco, which is a high-risk area for AIDS, showed a marked excess of KS in 1981. The KS case rate among never-married men younger than 50 years old, a surrogate index of homosexuality, was found to be markedly elevated in the post-AIDS period, compared with the case rate of a reference disease, mycosis fungoides. Never-married men younger than 50 years old, therefore, constitute a SEER-identifiable population who can be monitored for risk of KS and other neoplasms that might be related to AIDS. In addition, the incidence rate of KS in the SEER registry of Puerto Rico was generally higher than that in the U.S. SEER registries, despite data that suggested that KS may be underreported. The demographic characteristics of patients diagnosed as having KS in Puerto Rico suggested the classical rather than the AIDS-related form of KS.

  5. DNA Content Analysis by Flow Cytometry and Cytogenetic Analysis in Mycosis Fungoides and Sézary Syndrome

    PubMed Central

    Bunn, Paul A.; Whang-Peng, Jacqueline; Carney, Desmond N.; Schlam, Mark L.; Knutsen, Turid; Gazdar, Adi F.

    1980-01-01

    Flow cytometric (FCM) analysis of DNA content was performed on 82 lymph node and peripheral blood specimens from 46 patients with mycosis fungoides and the Sézary syndrome. Overall, 32 of the 46 patients (70%) had aneuploidy detected by FCM. Aneuploidy was present in 63% of the patients at the time of diagnosis before systemic therapy. In these patients, aneuploidy was frequently detected in blood and lymph node specimens scored as negative by cytology and histology, suggesting that unsuspected extracutaneous dissemination is present in many patients at the time of diagnosis. Direct comparison with Giemsa-banded cytogenetic studies showed an excellent correlation of FCM results and cytogenetic chromosome number. However, FCM frequently detected a larger fraction of aneuploid cells, and mitogen-stimulation studies suggest this is the result of preferential stimulation of normal lymphocytes by phytohemagglutinin. Thus, mitogens with a preference for malignant T cells, such as staphylococcal protein A, should be used for cytogenetic analysis of malignant T-cell disorders. At diagnosis, some histologically positive specimens contained only diploid cells by FCM and cytogenetic analysis. These patients had a more indolent clinical course than patients with aneuploidy. Aneuploidy was detected by FCM as either wide G1 or as discrete aneuploid peaks. The presence of aneuploidy at any time in the clinical course implied a poor prognosis. Discrete hyperdiploid peaks were associated with large cell histology, early relapse, and aggressive clinical course. The development of hyperdiploidy at relapse was documented in four patients and was associated with a transition to large cell histology and a poor prognosis. Similar studies may elucidate differences in natural history and mechanism for transition in histology in other lymphomas and solid tumors. PMID:6997334

  6. Characterization of the peripheral neuropathy associated with brentuximab vedotin treatment of Mycosis Fungoides and Sézary Syndrome.

    PubMed

    Corbin, Zachary A; Nguyen-Lin, Annie; Li, Shufeng; Rahbar, Ziba; Tavallaee, Mahkam; Vogel, Hannes; Salva, Katrin A; Wood, Gary S; Kim, Youn H; Nagpal, Seema

    2017-03-07

    Chemotherapy-induced peripheral neuropathy (CIPN) is common, frequently limits chemotherapy dosing, and negatively impacts quality of life. The National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0, and the Total Neuropathy Score clinical version (TNSc) are both validated scores to quantify peripheral neuropathy (PN), with the TNSc being more sensitive to clinical changes. Mycosis fungoides and Sézary syndrome (MF/SS) are characterized by a chronic course, where current therapies are generally non-curative and treatment toxicities have the potential for significant lasting effects. Brentuximab vedotin (BV) is an antibody-drug-conjugate composed of an anti-CD30 monoclonal antibody linked to the microtubule-disrupting agent, monomethyl auristatin E, with a known associated CIPN. In our phase II clinical trial of BV in MF/SS, 25 (69%) of 36 patients developed PN, with 18 (50%) developing Clinically Significant PN, CTCAE v4.0 grade 2 or higher. The median time to grade 2 PN was 15 weeks (range 0.4-48) after the initial dose. By Kaplan-Meier calculation, the median time to improvement from Clinically Significant PN was 30 weeks from the last BV dose. Seventy-four percent had improvement by 24 months. We found that TNSc scores significantly correlated with CTCAE grade, with Spearman correlation coefficient 0.68 (p < 0.001). By logistic regression, for each 100 mg increase in BV total dose, the likelihood of developing Clinically Significant PN increased by 23% (95% CI 4-46%). Improved monitoring of CIPN associated with BV is of paramount importance in the MF/SS population.

  7. A dyshidrosis-like variant of adult T-cell leukemia/lymphoma with clinicopathological aspects of mycosis fungoides. A case report.

    PubMed

    Bittencourt, Achiléa L; Mota, Karla; Oliveira, Rodrigo F; Farré, Lourdes

    2009-12-01

    Adult T-cell leukemia/lymphoma (ATL) is an aggressive type of leukemia/lymphoma associated with the human T-cell lymphotropic virus (HTLV-I). We describe an adult male patient clinically and pathologically diagnosed as mycosis fungoides and treated with chemotherapy after which complete involution of the lesions occurred. The disease relapsed with confluent dyshidrosis-like vesicles on the palmoplantar regions, followed by disseminated vesiculopapules and associated lymphocytosis. A serological test performed at this time revealed HTLV-I infection, and a diagnosis of chronic ATL was made. Monoclonal integration of HTLV-I was detected in peripheral blood mononuclear cells by inverse long polymerase chain reaction. A skin biopsy revealed spongiosis, Pautrier abscesses, and intraepidermal vesicles with atypical lymphocytes and an infiltration of small and atypical CD4 lymphocytes in the superficial dermis. Proliferative index (Ki-67) was 70%. This is the first reported vesicular cutaneous ATL with confirmation of HTLV-I proviral integration. The delay that occurred in diagnosing ATL was due to the fact that mycosis fungoides and ATL may present the same clinical, histopathological, and immunohistochemical features.

  8. Cutaneous disease resembling mycosis fungoides in HIV-infected patients whose skin and blood cells also harbor proviral HTLV type I.

    PubMed

    Zucker-Franklin, D; Pancake, B A; Friedman-Kien, A E

    1994-09-01

    Two homosexual HIV-infected patients with lymphocyte counts of < 50 presented with intense pruritus, hyperpigmentation, and skin lesions clinically suggestive of the cutaneous T cell lymphoma, mycosis fungoides. On light microscopy, the skin biopsies were difficult to interpret because of the sparseness of the lymphocytic infiltrates. However, electron microscopy revealed typical Sézary cells in the peripheral blood and skin. Cultures of blood mononuclear cells of one of the patients generated HTLV-I-like particles. Although both patients lacked antibodies to HTLV, their blood and skin specimens proved to harbor tax and pol HTLV-I proviral sequences as shown by the polymerase chain reaction and Southern blot analysis. Dual infection with HIV and HTLV should be considered in the diagnostic work-up of patients at risk, even in the absence of demonstrable antibodies. Dual infections could result in clinical manifestations and evolution of disease not anticipated in patients who harbor only one of these retroviruses.

  9. Case experience of 308-nm excimer laser therapy compatibility with PUVA and oral bexarotene for the treatment of cutaneous lesions in mycosis fungoides.

    PubMed

    Huang, Jing; Cowper, Shawn; Moss, Jeremy; Girardi, Michael

    2013-04-01

    Little is known about the safety and effectiveness of excimer laser therapy when used in conjunction with other therapies in the treatment of mycosis fungoides (MF) lesions. We describe the use of adjunctive excimer laser therapy in combination with psoralen plus ultraviolet A (PUVA) and oral bexarotene for the treatment of recalcitrant and sanctuary plaques in a patient with MF. In our patient, this regimen successfully induced clinical and histologic resolution in MF plaques with minimal side effects limited to mild, short-lived tenderness and, rarely, local erythema. Our experience suggests that adjunctive excimer laser therapy with PUVA and oral bexarotene has the potential to be a safe, well-tolerated, and effective focal treatment regimen for cutaneous MF lesions.

  10. CD4/CD8 double negative mycosis fungoides with PD-1 (CD279) expression--a disease of follicular helper T-cells?

    PubMed

    Kempf, Werner; Kazakov, Dmitry V; Cipolat, Claudio; Kutzner, Heinz; Roncador, Giovanna; Tomasini, Dario

    2012-10-01

    CD4/CD8 double negative mycosis fungoides (MF) is a rare phenotypic variant of this epidermotropic cutaneous T-cell lymphoma. Clinically, this MF form manifests with unusual appearances such as annular lesions confined to one body region as in our patient in whom the lesions were found on the left lower leg. The cellular origin of CD4/CD8 double negative MF is unknown. In our case, the intraepidermal CD4/CD8 double negative clonal T-lymphocytes (CD2+, CD4-, CD8-, CD30-, beta-F1+) expressed programmed death-1 but were negative for CXCL-13 and cytotoxic molecules (TIA-1, granzyme B, perforin). Our observation may give an insight into the histogenesis of this unique MF variant and may also be of therapeutic significance because programmed death-1 may serve as a target for therapeutic intervention.

  11. Membrane expression of NK receptors CD160 and CD158k contributes to delineate a unique CD4+ T-lymphocyte subset in normal and mycosis fungoides skin.

    PubMed

    Sako, Nouhoum; Schiavon, Valérie; Bounfour, Touda; Dessirier, Valérie; Ortonne, Nicolas; Olive, Daniel; Ram-Wolff, Caroline; Michel, Laurence; Sicard, Hélène; Marie-Cardine, Anne; Bagot, Martine; Bensussan, Armand; Schmitt, Christian

    2014-10-01

    CD160 is a GPI-anchored Ig-like receptor identified by the BY55 mAb on human circulating CD56dim+ NK cells and TCRγδ lymphocytes. In addition, while most intestinal T lymphocytes express it, only a minor circulating CD4+ or CD8+ T lymphocyte subset is CD160+. Here we describe a population of CD4+ CD160+ human blood T lymphocytes of circulating cutaneous T cells. These rare T lymphocytes represent 2.1 ± 1.9% of the circulating CD3+ CD4+ T cells, coexpress CD8αα, CD244, and perforin but lack CD28 expression, a phenotype corresponding to effector memory cytotoxic T-lymphocytes. Functional studies further confirmed their cytotoxic potential. These cells lack αEβ7 integrin and CCR7 expression but do express skin-addressing molecules CLA, and CCR4. In normal human skin, CD4+ CD160+ cells represent 34.6 ± 14.7% of the CD4+ T lymphocytes extracted by collagenase treatment. These T cells coexpress CLA (81 ± 13.6%), CCR4 (62.3 ± 15.9%), and some CD8αα (19.6 ± 13%) or CCR7 (24.4 ± 11.7%) expression. Cutaneous T-cell lymphoma cells express the natural killer receptor KIR3DL2 (CD158k) used as a tumor marker. Not only we confirmed the expression of this marker in the blood and/or skin of mycosis fungoides patients but we also show for the first time CD158k expression (often associated with CD160) on cutaneous CD4+ T cells from healthy individuals (25.3 ± 15%). Therefore, CD4+ CD160+ T cells expressing CD158k might represent specialized cutaneous lymphocytes devoted to immune surveillance, from which could originate cutaneous T-cell lymphomas such as mycosis fungoides.

  12. Total skin electron irradiation treatment for mycosis fungoides with a new alternate daily treatment schedule to minimize radiation-associated toxicity: a preliminary experience.

    PubMed

    Parida, D K; Verma, K K; Rath, G K

    2009-07-01

    Conventional total skin electron irradiation (TSEI) for mycosis fungoides (MF) causes radiation toxicity, requiring treatment interruptions that prolong the treatment period, making patient compliance poor. We evaluated an alternate daily treatment schedule of TSEI, using a high dose rate (HDR) to minimize radiation toxicity and shorten the treatment duration. Four patients (aged 45-73 years with MF duration of 7-22 months) were treated by TSEI using HDR. The treatment was given on 5 days/week for 2 weeks followed by treatment on alternate days to deliver a total dose of 36 Gy. All the patients completed treatment in 10 weeks and had complete remission. Radiation toxicity was much less common with this schedule, requiring no treatment interruption. All the patients were until in remission after 60-84 months of follow-up. This schedule of TSEI treatment caused minimal radiation toxicity and allowed completion of treatment over a shorter period, giving good clinical remission and prolonged disease-free survival.

  13. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part I. Diagnosis: clinical and histopathologic features and new molecular and biologic markers.

    PubMed

    Jawed, Sarah I; Myskowski, Patricia L; Horwitz, Steven; Moskowitz, Alison; Querfeld, Christiane

    2014-02-01

    Mycosis fungoides (MF) and Sézary syndrome (SS) comprise approximately 53% of cutaneous lymphomas. Both MF and SS may clinically and histologically mimic benign skin conditions, posing a diagnostic challenge to the dermatologist. Precise clinicopathologic correlation is necessary to support a diagnosis, especially in the early stages of disease. In addition to the identification of histopathologic criteria, ancillary studies, including the identification of CD4(+) T cells with aberrant immunophenotypes and T-cell receptor gene rearrangements within skin lesions and peripheral blood are used to support the diagnosis. Recent studies evaluating the pathogenesis of MF have found that the skin microenvironment, including immune cells, such as dendritic cells and reactive cytotoxic and regulatory T cells, plays a crucial supporting role in MF. The skin-homing ability of malignant T cells is the result of chemokines, cytokines, adhesion molecules, and defective apoptosis, and is believed to play a role in disease pathogenesis and progression. In addition, recent studies have also suggested that MF and SS arise from distinct memory T cell subsets and advanced/erythrodermic MF and SS may be distinguished by identification of certain molecules, including Programmed-Death-1.

  14. Combined Use of PCR-Based TCRG and TCRB Clonality Tests on Paraffin-Embedded Skin Tissue in the Differential Diagnosis of Mycosis Fungoides and Inflammatory Dermatoses

    PubMed Central

    Zhang, Bing; Beck, Andrew H.; Taube, Janis M.; Kohler, Sabine; Seo, Katie; Zwerner, Jeffrey; Viakhereva, Natalie; Sundram, Uma; Kim, Youn H.; Schrijver, Iris; Arber, Daniel A.; Zehnder, James L.

    2010-01-01

    The distinction between mycosis fungoides (MF) and inflammatory dermatoses (ID) by clinicopathologic criteria can be challenging. There is limited information regarding the performance characteristics and utility of TCRG and TCRB clonality assays in diagnosis of MF and ID from paraffin-embedded tissue sections. In this study, PCR tests were performed with both TCRG and TCRB BIOMED-2 clonality methods followed by capillary electrophoresis and Genescan analysis using DNA samples from 35 MF and 96 ID patients with 69 and 133 paraffin-embedded specimens, respectively. Performance characteristics were determined for each test individually and in combination. TCRG and TCRB tests demonstrated identical sensitivity (64%) and specificity (84%) when analyzed as individual assays. The positive predictive value, negative predictive value, and change of posttest MF probability over a range of MF pretest probabilities were obtained. These data were used to construct an algorithm for sequential use of TCRG and TCRB. As single tests, commercially available BIOMED-2 PCR-based TCRG and TCRB clonality tests on paraffin-embedded tissue have no significant difference in terms of sensitivity and specificity. Combined use of the two tests in patients with intermediate pretest probabilities as proposed in the algorithm could improve test utility. PMID:20203005

  15. Mycosis fungoides in patients under 20 years of age: report of 7 cases, review of the literature and study of the clinical course.

    PubMed

    Quaglino, P; Zaccagna, A; Verrone, A; Dardano, F; Bernengo, M G

    1999-01-01

    Mycosis fungoides (MF) is rare in young patients. Its clinical behavior is still uncertain, as some reports have suggested that it has a more aggressive course than does the adult-onset type. To ascertain if early-onset MF represents a heterogeneous group of cutaneous T cell lymphomas. Clinical, immunohistopathological and follow-up data of early-onset (<20 years of age) MF cases reported in the literature (n = 42) plus 7 described herein were compared with those of a cohort of adult-onset MF patients (n = 252) diagnosed at our institution since 1975. The majority of the 49 early-onset MF patients had patch-plaque stage disease at diagnosis. Ten had hypopigmented lesions. The predominant phenotype was CD3+ CD4+CD7-CD8-. Seven patients had a stage progression, 6 with extracutaneous involvement. Five- and 10-year survival rates were 93 and 74%, respectively. No statistically significant differences were found in the disease course between early- and adult-onset MF.

  16. Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy.

    PubMed

    Hughes, Charlotte F M; Khot, Amit; McCormack, Christopher; Lade, Stephen; Westerman, David A; Twigger, Robert; Buelens, Odette; Newland, Kate; Tam, Constantine; Dickinson, Michael; Ryan, Gail; Ritchie, David; Wood, Colin; Prince, H Miles

    2015-01-01

    Numerous systemic treatment options exist for patients with mycosis fungoides (MF) and Sézary syndrome (SS), but no large comparative studies are published. To study the efficacy of treatments, a retrospective analysis of our cutaneous lymphoma database was undertaken, with 198 MF/SS patients undergoing systemic therapies. The primary end point was time to next treatment (TTNT). Patients with advanced-stage disease made up 53%. The median follow-up time from diagnosis for all alive patients was 4.9 years (range 0.3-39.6), with a median survival of 11.4 years. Patients received a median of 3 lines of therapy (range 1-13), resulting in 709 treatment episodes. Twenty-eight treatment modalities were analyzed. The median TTNT for single- or multiagent chemotherapy was only 3.9 months (95% confidence interval [CI] 3.2-5.1), with few durable remissions. α-interferon gave a median TTNT of 8.7 months (95% CI 6.0-18.0), and histone deacetylase inhibitors (HDACi) gave a median TTNT of 4.5 months (95% CI 4.0-6.1). When compared directly with chemotherapy, interferon and HDACi both had greater TTNT (P < .00001 and P = .01, respectively). This study confirms that all chemotherapy regimens assessed have very modest efficacy; we recommend their use be restricted until other options are exhausted. © 2015 by The American Society of Hematology.

  17. The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell lymphotropic virus-associated disease. A study of 50 patients.

    PubMed Central

    Pancake, B A; Zucker-Franklin, D; Coutavas, E E

    1995-01-01

    For nearly two decades it has been suspected that the cutaneous T cell lymphoma, mycosis fungoides (MF), and its leukemic variant, the Sézary syndrome, are caused by the human T lymphotropic virus (HTLV-I/II). Arguments against this concept included the finding that only a small number of MF patients have antibodies to HTLV-I/II and that attempts to detect proviral sequences by mere Southern hybridization of extracted DNA usually met with failure. However, we have reported repeatedly that HTLV-like particles emerge in blood mononuclear cell (PBMC) cultures of practically all patients with this disease. In several instances, the particles were identified as HTLV by immunoelectron microscopy as well as biomolecular analysis. With the assumptions that the virus in MF patients may have become detection by Southern hybridization alone, the extracts of freshly isolated PBMC of 50 consecutive patients were subjected to combined PCR/Southern analysis. Here we report the presence of HTLV pol and/or tax proviral sequences in 46 out of 50 (92%) of the patients tested. In addition, five of the patients, who lacked antibodies to HTLV-I/II structural proteins, were found to be seropositive for tax. It thus seems reasonable to conclude that MF/Sézary syndrome is an HTLV-associated disease and that lack of an immune response does not preclude infection with this type of virus. Images PMID:7860737

  18. Flow cytometric detection of neoplastic T cells in patients with mycosis fungoides based on levels of T-cell receptor expression.

    PubMed

    Kuchnio, M; Sausville, E A; Jaffe, E S; Greiner, T; Foss, F M; McClanahan, J; Fukushima, P; Stetler-Stevenson, M A

    1994-12-01

    The authors report the flow cytometric detection of neoplastic T cells in the peripheral blood of four out of five (80%) patients with peripheral blood involvement with mycosis fungoides (Sezary syndrome) based on the levels of T-cell receptor expression as measured by CD3 and TCR-alpha beta staining. Antigen receptor expression was abnormal in terms of increased density of surface CD3 or TCR-alpha beta per cell. Other immunophenotypic abnormalities were present in three of these patients. However, in one patient abnormal T-cell receptor expression was the only immunophenotypic evidence of neoplasia, although morphologically abnormal lymphocytes were present and a T-cell clone was detected by polymerase chain reaction (PCR). In another patient, the authors were able to detect development of a new, more aggressive neoplastic T-cell population based on levels of T-cell receptor expression. Levels of T-cell receptor expression may be of diagnostic utility in the evaluation of peripheral blood for the presence of neoplastic T-cell populations.

  19. Phase II Intergroup Trial of Alisertib in Relapsed and Refractory Peripheral T-Cell Lymphoma and Transformed Mycosis Fungoides: SWOG 1108.

    PubMed

    Barr, Paul M; Li, Hongli; Spier, Catherine; Mahadevan, Daruka; LeBlanc, Michael; Ul Haq, Mansoor; Huber, Bryan D; Flowers, Christopher R; Wagner-Johnston, Nina D; Horwitz, Steven M; Fisher, Richard I; Cheson, Bruce D; Smith, Sonali M; Kahl, Brad S; Bartlett, Nancy L; Friedberg, Jonathan W

    2015-07-20

    Aurora A kinase (AAK) is upregulated in highly proliferative lymphomas, suggesting its potential as a therapeutic target. Alisertib is a novel oral AAK inhibitor without adverse safety signals in early-phase studies that demonstrated preliminary activity in T-cell lymphoma. This phase II study was conducted to further investigate the efficacy of alisertib in relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL). Eligible patients with histologically confirmed relapsed/refractory PTCL or transformed Mycosis fungoides (tMF) received alisertib 50 mg twice a day for 7 days on 21-day cycles. Of 37 eligible patients, the histologic subtypes enrolled included PTCL not otherwise specified (n = 13), angioimmunoblastic T-cell lymphoma (n = 9), tMF (n = 7), adult T-cell lymphoma/leukemia (n = 4), anaplastic large-cell lymphoma (n = 2), and extranodal natural killer/T-cell lymphoma (n = 2). Grade 3 and 4 adverse events in ≥ 5% of patients included neutropenia (32%), anemia (30%), thrombocytopenia (24%), febrile neutropenia (14%), mucositis (11%), and rash (5%). Treatment was discontinued most commonly for disease progression. Among the PTCL subtypes, the overall response rate was 30%, whereas no responses were observed in tMF. Aurora B kinase was more commonly overexpressed than AAK in tumor specimens. Analysis of AAK, Aurora B kinase, MYC, BCL-2, phosphatidylinositol 3-kinase γ, and Notch1 expression revealed no association with response. Alisertib has antitumor activity in PTCL, including heavily pretreated patients. These promising results are being further investigated in an ongoing international, randomized phase III trial comparing alisertib with investigator's choice in PTCL. © 2015 by American Society of Clinical Oncology.

  20. Phase II Intergroup Trial of Alisertib in Relapsed and Refractory Peripheral T-Cell Lymphoma and Transformed Mycosis Fungoides: SWOG 1108

    PubMed Central

    Barr, Paul M.; Li, Hongli; Spier, Catherine; Mahadevan, Daruka; LeBlanc, Michael; Ul Haq, Mansoor; Huber, Bryan D.; Flowers, Christopher R.; Wagner-Johnston, Nina D.; Horwitz, Steven M.; Fisher, Richard I.; Cheson, Bruce D.; Smith, Sonali M.; Kahl, Brad S.; Bartlett, Nancy L.; Friedberg, Jonathan W.

    2015-01-01

    Purpose Aurora A kinase (AAK) is upregulated in highly proliferative lymphomas, suggesting its potential as a therapeutic target. Alisertib is a novel oral AAK inhibitor without adverse safety signals in early-phase studies that demonstrated preliminary activity in T-cell lymphoma. This phase II study was conducted to further investigate the efficacy of alisertib in relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL). Patients and Methods Eligible patients with histologically confirmed relapsed/refractory PTCL or transformed Mycosis fungoides (tMF) received alisertib 50 mg twice a day for 7 days on 21-day cycles. Results Of 37 eligible patients, the histologic subtypes enrolled included PTCL not otherwise specified (n = 13), angioimmunoblastic T-cell lymphoma (n = 9), tMF (n = 7), adult T-cell lymphoma/leukemia (n = 4), anaplastic large-cell lymphoma (n = 2), and extranodal natural killer/T-cell lymphoma (n = 2). Grade 3 and 4 adverse events in ≥ 5% of patients included neutropenia (32%), anemia (30%), thrombocytopenia (24%), febrile neutropenia (14%), mucositis (11%), and rash (5%). Treatment was discontinued most commonly for disease progression. Among the PTCL subtypes, the overall response rate was 30%, whereas no responses were observed in tMF. Aurora B kinase was more commonly overexpressed than AAK in tumor specimens. Analysis of AAK, Aurora B kinase, MYC, BCL-2, phosphatidylinositol 3-kinase γ, and Notch1 expression revealed no association with response. Conclusion Alisertib has antitumor activity in PTCL, including heavily pretreated patients. These promising results are being further investigated in an ongoing international, randomized phase III trial comparing alisertib with investigator's choice in PTCL. PMID:26077240

  1. Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides--cutaneous T-cell lymphoma: clinical implications.

    PubMed

    Alcántara-Hernández, M; Torres-Zárate, C; Pérez-Montesinos, G; Jurado-Santacruz, F; Domínguez-Gómez, M A; Peniche-Castellanos, A; Ferat-Osorio, E; Neri, N; Nambo, M J; Alvarado-Cabrero, I; Moreno-Lafont, M; Huerta-Yepez, S; Bonifaz, L C

    2014-05-01

    Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4(+) T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4(+) T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4(+) T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4(+) T cells. In addition, we found a decrease in the percentage of FoxP3(+) cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3(+) T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.

  2. High soluble CD30, CD25 and IL-6 may identify patients with worse survival in CD30+ cutaneous lymphomas and early mycosis fungoides

    PubMed Central

    Kadin, Marshall E.; Pavlov, Igor; Delgado, Julio C.; Vonderheid, Eric C.

    2011-01-01

    Histopathology alone cannot predict outcome of patients with CD30+ primary cutaneous lymphoproliferative disorders (CD30CLPD) and early mycosis fungoides (MF). To test the hypothesis that serum cytokines/cytokine receptors provide prognostic information in these disorders, we measured soluble CD30 (sCD30), sCD25, and selected cytokines in cell cultures and sera of 116 patients with CD30CLPD and 96 patients with early MF followed up to 20 years. Significant positive correlation was found between sCD30 levels and sCD25, CD40L, IL-6, and IL-8, suggesting CD30+ neoplastic cells secrete these cytokines, but not Th2 cytokines. In vitro studies confirmed sCD30, sCD25, IL-6 and IL-8 are secreted by CD30CLPD-derived cell lines. CD30CLPD patients with above normal sCD30 and sCD25 had worse overall and disease-related survivals, but only sCD30 retained significance in Cox models that included advanced age. High sCD30 also identified patients with worse survival in early MF. Increased IL-6 and IL-8 correlated with poor disease-related survival in CD30CLPD patients, We conclude that: (1) neoplastic cells of some CD30CLPD patients do not resemble Th2 cells, (2) high serum sCD30, sCD25, IL-6, and perhaps IL-8 levels may provide prognostic information useful for patient management. PMID:22071475

  3. Medical History, Lifestyle, Family History, and Occupational Risk Factors for Mycosis Fungoides and Sézary Syndrome: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

    PubMed Central

    Aschebrook-Kilfoy, Briseis; Cocco, Pierluigi; La Vecchia, Carlo; Chang, Ellen T.; Vajdic, Claire M.; Kadin, Marshall E.; Spinelli, John J.; Morton, Lindsay M.; Kane, Eleanor V.; Sampson, Joshua N.; Kasten, Carol; Feldman, Andrew L.; Wang, Sophia S.

    2014-01-01

    Background Mycosis fungoides and Sézary syndrome (MF/SS) are rare cutaneous T-cell lymphomas. Their etiology is poorly understood. Methods A pooled analysis of 324 MF/SS cases and 17217 controls from 14 case–control studies from Europe, North America, and Australia, as part of the International Lymphoma Epidemiology Consortium (InterLymph) Non-Hodgkin Lymphoma (NHL) Subtypes Project, was carried out to investigate associations with lifestyle, medical history, family history, and occupational risk factors. Multivariate logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Results We found an increased risk of MF/SS associated with body mass index equal to or larger than 30kg/m2 (OR = 1.57, 95% CI = 1.03 to 2.40), cigarette smoking for 40 years or more (OR = 1.55, 95% CI = 1.04 to 2.31), eczema (OR = 2.38, 95% CI = 1.73 to 3.29), family history of multiple myeloma (OR = 8.49, 95% CI = 3.31 to 21.80), and occupation as crop and vegetable farmers (OR = 2.37, 95% CI = 1.14 to 4.92), painters (OR = 3.71, 95% CI = 1.94 to 7.07), woodworkers (OR = 2.20, 95% CI = 1.18 to 4.08), and general carpenters (OR = 4.07, 95% CI = 1.54 to 10.75). We also found a reduced risk of MF/SS associated with moderate leisure time physical activity (OR = 0.46, 95% CI = 0.22 to 0.97). Conclusions Our study provided the first detailed analysis of risk factors for MF/SS and further investigation is needed to confirm these findings in prospective data and in other populations. PMID:25174030

  4. An Index Case of Concomitant Tumoral and Ichthyosiform Mycosis Fungoides-Like Presentation of Chronic Adult T-cell Leukemia/Lymphoma Associated With Upregulation of TOX.

    PubMed

    Nguyen, Giang Huong; Wang, James Y; Hymes, Kenneth B; Magro, Cynthia M

    2017-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive lymphoid malignancy known to be associated with human T-cell lymphotropic virus type 1. There are 2 broad categories: acute and chronic. In the acute category, there is a leukemic and a lymphomatous variant, whereas in the designated "chronic" form, there is mild peripheral blood lymphocytosis. The intermediate "smoldering" category is without peripheral blood lymphocytosis with only discernible skin involvement. We present a 68-year-old human T-cell lymphotropic virus type 1 seropositive female with a mild peripheral blood atypical lymphocytosis who had indurated nodules on her hands of 2 years duration and a new scaly ichthyosiform eruption on her lower extremities. Histopathologic examination of the hand biopsy revealed coalescing nodules of large atypical noncerebriform lymphocytes with focal areas of epidermotropism. Phenotypically, the infiltrate was positive for β-F1, CD2, CD4, CD5, CD7, Foxp3, and CD25. In both biopsies, there was striking upregulation of TOX (thymocyte selection-associated high mobility group box factor) in the nuclei of neoplastic cells. The second biopsy taken from the ichthyotic patch on the patient's left leg showed a subtle pattern of epidermal infiltration by atypical noncerebriform lymphocytes and a distinct compact scale consistent with the clinical picture of ichthyosis. The histopathologic appearance was that of a yet undescribed ichthyosiform mycosis fungoides-like presentation of chronic ATLL. In addition, the observed upregulation of nuclear TOX may play an oncogenic role in ATLL. The course to date in this patient has been relatively indolent, although the patients believe that large cell transformation could portend more aggressive disease.

  5. The Therapeutic Potential of AN-7, a Novel Histone Deacetylase Inhibitor, for Treatment of Mycosis Fungoides/Sezary Syndrome Alone or with Doxorubicin.

    PubMed

    Moyal, Lilach; Feldbaum, Nataly; Goldfeiz, Neta; Rephaeli, Ada; Nudelman, Abraham; Weitman, Michal; Tarasenko, Nataly; Gorovitz, Batia; Maron, Leah; Yehezkel, Shiran; Amitay-Laish, Iris; Lubin, Ido; Hodak, Emmilia

    2016-01-01

    The 2 histone deacetylase inhibitors (HDACIs) approved for the treatment of cutaneous T-cell lymphoma (CTCL) including mycosis fungoides/sezary syndrome (MF/SS), suberoylanilide hydroxamic acid (SAHA) and romidepsin, are associated with low rates of overall response and high rates of adverse effects. Data regarding combination treatments with HDACIs is sparse. Butyroyloxymethyl diethylphosphate (AN-7) is a novel HDACI, which was found to have selective anticancer activity in several cell lines and animal models. The aim of this study was to compare the anticancer effects of AN-7 and SAHA, either alone or combined with doxorubicin, on MF/SS cell lines and peripheral blood lymphocytes (PBL) from patients with Sezary syndrome (SPBL). MyLa cells, Hut78 cells, SPBL, and PBL from healthy normal individuals (NPBL) were exposed to the test drugs, and the findings were analyzed by a viability assay, an apoptosis assay, and Western blot. AN-7 was more selectively toxic to MyLa cells, Hut78 cells, and SPBL (relative to NPBL) than SAHA and also acted more rapidly. Both drugs induced apoptosis in MF/SS cell lines, SAHA had a greater effect on MyLa cell line, while AN-7 induced greater apoptosis in SPBL; both caused an accumulation of acetylated histone H3, but AN-7 was associated with earlier kinetics; and both caused a downregulation of the HDAC1 protein in MF/SS cell lines. AN-7 acted synergistically with doxorubicin in both MF/SS cell lines and SPBL, and antagonistically with doxorubicin in NPBL. By contrast, SAHA acted antagonistically with doxorubicin on MF/SS cell lines, SPBL, and NPBL, leaving <50% viable cells. In conclusion, AN-7 holds promise as a therapeutic agent in MF/SS and has several advantages over SAHA. Our data provide a rationale for combining AN-7, but not SAHA, with doxorubicin to induce the cell death in MF/SS.

  6. Mycosis fungoides patient accompanied actinic keratosis, actinic keratosis with squamous cell carcinoma transformation, and porokeratosis after NBUVB therapy - 1st case report and review of the literature.

    PubMed

    Zhao, Meng-Jie; Abdul-Fattah, Bilal; Qu, Xiao-Ying; Wang, Cui-Yan; Wang, Xia; Ran, Yi; Lai, Ting; Chen, Si-Yuan; Huang, Chang-Zheng

    2016-10-01

    Mycosis fungoides (MF) is the most common form of primary cutaneous T cell lymphoma. Narrowband ultraviolet B light (NBUVB) is used increasingly in treating MF because of its good toleration and well-established management. To discuss the risk factors and underlying pathogenic factors in the patients with secondary skin diseases after NBUVB therapy. We report in details the first case of a patient with MF accompanied with actinic keratosis (AK), AK with squamous cell carcinoma (SCC) transformation and porokeratosis after NBUVB therapy. Meanwhile, Sequence variants in tumor suppressor p53 gene in the patient's specimens were detected. A literature search of the key word "narrowband ultraviolet B light "and "side effects" was performed on PubMed, 14 cases of this entity were found. A total of 15 patients including our case were reviewed in this study and meaningful conclusion could be drawn. The mean age at diagnosis of secondary skin dermatoses after NBUVB therapy was 62.08 years with a male to female ratio of 2:1. The cases were reported more in Europeans than in Asians (2.75:1), and the Fitzpatrick skin type was mainly Ito III (12/15). The mean cumulative number and cumulative dose of UVB treatments were 43.71 and 42, 400 (mJ/cm), respectively. There was a positive relationship between Fitzpatrick skin type and cumulative dose of UVB treatments. Among the secondary skin diseases after NBUVB treatment, 12 were tumors, 2 were non-tumorous dermatoses. Only our patient presented with both. By polymerase chain reaction-single nucleotide polymorphism (PCR-SNP) analysis, C-G mutation of exon 4 of p53 was found in AK and MF specimens in our patient. To our knowledge, our case is the first MF patient accompanied with AK, AK with SCC transformation and Porokeratosis after NBUVB treatment. Lower Fitzpatrick skin type may be the risk factor of secondary skin diseases after NBUVB treatment.

  7. The comparison of expression of cutaneous lymphocyte-associated antigen (CLA), and Th1- and Th2-associated antigens in mycosis fungoides and cutaneous lesions of adult T-cell leukemia/lymphoma.

    PubMed

    Yamaguchi, Takahiro; Ohshima, Koichi; Tsuchiya, Takeshi; Suehuji, Hiroaki; Karube, Kennosuke; Nakayama, Juichiro; Suzumiya, Junji; Yoshino, Tadashi; Kikuchi, Masahiro

    2003-01-01

    Mycosis fungoides (MF) is morphologically similar to cutaneous lesions of adult T cell leukemia/lymphoma (ATLL) of human T-cell lymphotropic virus-type I (HTLV-1). In addition, the Th1 or Th2 characteristic of MF and ATLL is still controversial. In the present study, to discriminate MF and cutaneous lesion of ATLL using immunohistochemical markers, and to elucidate Th1 or Th2 dominancy in both disorders, CLA (cutaneous lymphocyte associated antigen) was expressed on epidermotrophic lymphoma cells in all early stage MF. In contrast, all ATLL were negative for CLA. CXCR3 was especially expressed in epidermotropic small lymphoma cells of MF. CCR5 was expressed in both disorders with variable sized lymphoma cells. ST2 was expressed on large transformed lymphoma cells with ATLL, but not in any MF cases. OX40 was expressed in the large transformed cell population in both disorders. These findings suggest that CLA and ST2 could be potentially useful immunohistochemical markers for discrimination of mycosis fungoides and cutaneous lesions of ATLL. And OX40 could be a useful immunohistochemical marker for the histopathological progression of both disorders.

  8. Phase I Clinical Trial of O6-Benzylguanine and Topical Carmustine in the Treatment of Cutaneous T-Cell Lymphoma, Mycosis Fungoides Type

    PubMed Central

    Apisarnthanarax, Narin; Wood, Gary S.; Stevens, Seth R.; Carlson, Sean; Chan, Derek V.; Liu, Lili; Szabo, Sarolta K.; Fu, Pingfu; Gilliam, Anita C.; Gerson, Stanton L.; Remick, Scot C.; Cooper, Kevin D.

    2012-01-01

    Objectives To evaluate the toxic effects and maximum tolerated dose of topical carmustine [1,3-bis (2-chloroethyl)-1-nitrosourea] following intravenous O6-benzylguanine in the treatment of cutaneous T-cell lymphoma (CTCL), and to determine pharmacodynamics of O6-alkylguanine DNA alkyltransferase activity in treated CTCL lesions. Design Open-label, dose-escalation, phase I trial. Setting Dermatology outpatient clinic and clinical research unit at a university teaching hospital. Patients A total of 21 adult patients (11 male, 10 female) with early-stage (IA-IIA) refractory CTCL, mycosis fungoides type, treated with topical carmustine following intravenous O6-benzylguanine. Intervention Treatment once every 2 weeks with 120 mg/m2 intravenous O6-benzylguanine followed 1 hour later by whole-body, low-dose topical carmustine starting at 10 mg, with 10-mg incremental dose-escalation in 3 patient cohorts. Cutaneous T-cell lymphoma lesional skin biopsy specimens were taken at baseline and 6 hours, 24 hours, and 1 week after the first O6-benzylguanine infusion for analysis of O6-alkylguanine-DNA alkyltransferase activity. Main Outcome Measures Clinical response measured by physical examination and severity-weighted assessment tool measurements, safety data acquired by review of adverse events at study visits, and O6-alkylguanine-DNA alkyltransferase activity in treated lesion skin biopsy specimens. Results A minimal toxic effect was observed through the 40-mg carmustine dose level with 76% of adverse events being grade 1 based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Mean baseline O6-alkylguanine-DNA alkyl-transferase activity in CTCL lesions was 3 times greater than in normal controls and was diminished by a median of 100% at 6 and 24 hours following O6-benzyl-guanine with recovery at 1 week. Clinical disease reduction correlated positively with O6-alkylguanine-DNA alkyltransferase activity at 168 hours (P= .02) and inversely with

  9. Human T-cell lymphotropic virus type 1 provirus and phylogenetic analysis in patients with mycosis fungoides and their family relatives.

    PubMed

    Shohat, M; Shohat, B; Mimouni, D; Pauli, G; Ellerbrok, H; David, M; Hodak, E

    2006-08-01

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma of unknown aetiology. A pathogenic role of human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. To determine whether MF is linked to HTLV-1. Blood samples were collected from 60 patients, 15 family relatives of patients with MF (MFRs), 20 healthy controls and 10 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The presence of HTLV-1 antibodies in serum was tested by the Western blot rp21e-enhanced test. DNA was extracted from the blood with the Qiagen blood kit. We used 500 ng of DNA either in conventional HTLV-1-specific polymerase chain reaction (PCR) or in real-time PCR using primers sk43 and sk44 together with a tax-specific fluorescent probe. In Western blot, antibodies against three to four HTLV-1 antigens were detected in 52% of patients with MF. All of the patients with HAM/TSP were positive, while only 7% of the MFRs and none of the 20 healthy controls reacted with HTLV-1 antigens in Western blot. One of 60 patients with MF and one of 15 MFRs were positive in HTLV-1 PCR. These two PCR-positive samples which were quantified in real-time PCR showed that fewer than five in 10(6) cells were HTLV-1 infected. We succeeded in amplifying and sequencing the 5' end of the provirus from the blood of the PCR-positive MFR by seminested PCR. A positive result was also obtained in this test. Phylogenetic tree analyses revealed a high homology of this sequence with other HTLV-1 sequences from the Middle East. The above PCR-positive MFR was the brother of a PCR-negative patient with MF. These findings demonstrate that HTLV-1 is probably not the aetiological agent of MF. However, it may play a role in immunosuppression and in the spreading of the disease.

  10. Mycosis fungoides patient accompanied actinic keratosis, actinic keratosis with squamous cell carcinoma transformation, and porokeratosis after NBUVB therapy – 1st case report and review of the literature

    PubMed Central

    Zhao, Meng-jie; Abdul-fattah, Bilal; Qu, Xiao-ying; Wang, Cui-yan; Wang, Xia; Ran, Yi; Lai, Ting; Chen, Si-yuan; Huang, Chang-zheng

    2016-01-01

    Abstract Introduction: Mycosis fungoides (MF) is the most common form of primary cutaneous T cell lymphoma. Narrowband ultraviolet B light (NBUVB) is used increasingly in treating MF because of its good toleration and well-established management. Concerns: To discuss the risk factors and underlying pathogenic factors in the patients with secondary skin diseases after NBUVB therapy. Methods: We report in details the first case of a patient with MF accompanied with actinic keratosis (AK), AK with squamous cell carcinoma (SCC) transformation and porokeratosis after NBUVB therapy. Meanwhile, Sequence variants in tumor suppressor p53 gene in the patient's specimens were detected. A literature search of the key word “narrowband ultraviolet B light ”and “side effects” was performed on PubMed, 14 cases of this entity were found. A total of 15 patients including our case were reviewed in this study and meaningful conclusion could be drawn. Outcomes: The mean age at diagnosis of secondary skin dermatoses after NBUVB therapy was 62.08 years with a male to female ratio of 2:1. The cases were reported more in Europeans than in Asians (2.75:1), and the Fitzpatrick skin type was mainly Ito III (12/15). The mean cumulative number and cumulative dose of UVB treatments were 43.71 and 42, 400 (mJ/cm2), respectively. There was a positive relationship between Fitzpatrick skin type and cumulative dose of UVB treatments. Among the secondary skin diseases after NBUVB treatment, 12 were tumors, 2 were non-tumorous dermatoses. Only our patient presented with both. By polymerase chain reaction-single nucleotide polymorphism (PCR-SNP) analysis, C–G mutation of exon 4 of p53 was found in AK and MF specimens in our patient. Conclusion: To our knowledge, our case is the first MF patient accompanied with AK, AK with SCC transformation and Porokeratosis after NBUVB treatment. Lower Fitzpatrick skin type may be the risk factor of secondary skin diseases after NBUVB treatment. PMID

  11. Advantages and implications of high dose rate (HDR) total skin electron irradiation (TSEI) for the management of Mycosis Fungoides. Indian experience.

    PubMed

    Parida, Dillip Kumar; Rath, Goura Kishore

    2014-03-01

    Mycosis Fungoides (MF) is an indolent lymphoproliferative disorder affecting dermis caused by abnormal proliferation of CD4+ T-cells. Radiation therapy is the most effective modality of treatment for MF which offers cure in limited stage disease and desirable palliation in advance stage disease. Treating entire skin having many curved surfaces and folds with radiation is the real challenge for the radiation oncologist. Many techniques, dose schedules and modifications in total skin electron irradiation (TSEI) have been tried since 1950s. TSEI treatment is a very time consuming, inconvenient and physically challenging to both patient as well as oncologist. At our center TSEI was performed since 1983 with conventional linear accelerator where the treatment time was prolonged beyond two hours, which was very difficult or the patient, oncologist, technical officer and eating away the machine time hampering the treatment of other patients. From 1998 we shifted to high dose rate (HDR) mode, in order to bring down the treatment time of a single patient every day from two and half hour to 15 min. The reduction of treatment time increases patient compliance and at the same time saved machine time. Between 1998 and 2003, eleven pathological diagnosed MF patients were treated using HDR TSEI. All the patients were male between 40 and 70 years of age, who had the history of having the disease for 7-22 months. Four patients had T2 and seven patients had T3 stage disease with more than 90% skin surface involvement. TSEI was performed with 4 MeV electrons with a daily fraction size of 120 cGy to a total dose of 36 Gy. At the end of 36 Gy, boost dose of 10 Gy was delivered to self shielding regions like sole, scalp and perineum. Considering the treatment related toxicities and consequent treatment interruptions, in the first seven patients, the last four patients were treated using similar HDR TSEI technique with modified treatment schedule, where the treatment was given on

  12. Genetics Home Reference: mycosis fungoides

    MedlinePlus

    ... navigation Home Page Search Home Health Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Share: Email ... cancerous cells. Abnormalities have been found on most chromosomes, but some regions are more commonly affected than ...

  13. Pharmacokinetic and pharmacodynamic characterization of a new formulation containing synergistic proportions of interferons alpha-2b and gamma (HeberPAG) in patients with mycosis fungoides: an open-label trial.

    PubMed

    García-Vega, Yanelda; García-García, Idrian; Collazo-Caballero, Sonia E; Santely-Pravia, Egla E; Cruz-Ramírez, Alieski; Tuero-Iglesias, Angela D; Alfonso-Alvarado, Cristian; Cabrera-Placeres, Mileidys; Castro-Basart, Nailet; Duncan-Roberts, Yaquelín; Carballo-Treto, Tania I; Soto-Matos, Josanne; Izquierdo-Toledo, Yoandy; Vázquez-Blomquist, Dania; García-Iglesias, Elizeth; Bello-Rivero, Iraldo

    2012-12-28

    The synergistic combination of interferon (IFN) alpha-2b and IFN gamma results in more potent in vitro biological effects mediated by both IFNs. The aim of this investigation was to evaluate by first time the pharmacokinetics and pharmacodynamics of this combination in patients with mycosis fungoides. An exploratory, prospective, open-label clinical trial was conducted. Twelve patients, both genders, 18 to 75 years-old, with mycosis fungoides at stages IB to III, were eligible for the study. All of them received intramuscularly a single high dose (23 × 10(6) IU) of a novel synergistic IFN mixture (HeberPAG) for pharmacokinetic and pharmacodynamic studies. Serum IFN alpha-2b and IFN gamma concentrations were measured during 96 hours by commercial enzyme immunoassays (EIA) specific for each IFN. Other blood IFN-inducible markers and laboratory variables were used as pharmacodynamics and safety criteria. The pharmacokinetic evaluation by EIA yielded a similar pattern for both IFNs that are also in agreement with the well-known described profiles for these molecules when these are administered separately. The average values for main parameters were: Cmax: 263 and 9.3 pg/mL; Tmax: 9.5 and 6.9 h; AUC: 4483 and 87.5 pg.h/mL, half-life (t(1/2)): 4.9 and 13.4 h; mean residence time (MRT): 13.9 and 13.5 h, for serum IFN alpha-2b and IFN gamma, respectively. The pharmacodynamic variables were strongly stimulated by simultaneous administration of both IFNs: serum neopterin and beta-2 microglobulin levels (β2M), and stimulation of 2'-5' oligoadenylate synthetase (OAS1) mRNA expression. The most encouraging data was the high increment of serum neopterin, 8.0 ng/mL at 48 h, not been described before for any unmodified or pegylated IFN. Additionally, β2M concentration doubled the pre-dose value at 24-48 hours. For both variables the values remained clearly upper baseline levels at 96 hours. HeberPAG possesses improved pharmacodynamic properties that may be very useful in

  14. Pharmacokinetic and pharmacodynamic characterization of a new formulation containing synergistic proportions of interferons alpha-2b and gamma (HeberPAG®) in patients with mycosis fungoides: an open-label trial

    PubMed Central

    2012-01-01

    Background The synergistic combination of interferon (IFN) alpha-2b and IFN gamma results in more potent in vitro biological effects mediated by both IFNs. The aim of this investigation was to evaluate by first time the pharmacokinetics and pharmacodynamics of this combination in patients with mycosis fungoides. Methods An exploratory, prospective, open-label clinical trial was conducted. Twelve patients, both genders, 18 to 75 years-old, with mycosis fungoides at stages IB to III, were eligible for the study. All of them received intramuscularly a single high dose (23 × 106 IU) of a novel synergistic IFN mixture (HeberPAG®) for pharmacokinetic and pharmacodynamic studies. Serum IFN alpha-2b and IFN gamma concentrations were measured during 96 hours by commercial enzyme immunoassays (EIA) specific for each IFN. Other blood IFN-inducible markers and laboratory variables were used as pharmacodynamics and safety criteria. Results The pharmacokinetic evaluation by EIA yielded a similar pattern for both IFNs that are also in agreement with the well-known described profiles for these molecules when these are administered separately. The average values for main parameters were: Cmax: 263 and 9.3 pg/mL; Tmax: 9.5 and 6.9 h; AUC: 4483 and 87.5 pg.h/mL, half-life (t1/2): 4.9 and 13.4 h; mean residence time (MRT): 13.9 and 13.5 h, for serum IFN alpha-2b and IFN gamma, respectively. The pharmacodynamic variables were strongly stimulated by simultaneous administration of both IFNs: serum neopterin and beta-2 microglobulin levels (β2M), and stimulation of 2’-5’ oligoadenylate synthetase (OAS1) mRNA expression. The most encouraging data was the high increment of serum neopterin, 8.0 ng/mL at 48 h, not been described before for any unmodified or pegylated IFN. Additionally, β2M concentration doubled the pre-dose value at 24–48 hours. For both variables the values remained clearly upper baseline levels at 96 hours. Conclusions HeberPAG®possesses improved

  15. Demonstration of antibodies to human T-cell lymphotropic virus-I tax in patients with the cutaneous T-cell lymphoma, mycosis fungoides, who are seronegative for antibodies to the structural proteins of the virus.

    PubMed

    Pancake, B A; Wassef, E H; Zucker-Franklin, D

    1996-10-15

    Although most patients with the cutaneous T-cell lymphoma, mycosis fungoides (MF), are seronegative for human T-cell lymphotropic virus-I or -II (HTLV-I/II) when tested by assays that measure only antibodies to the viral structural proteins, the majority of such patients harbor HTLV-I-related pol and tax proviral sequences that encode proteins not included in routinely used serologic tests. Tax mRNA has also been detected in their peripheral blood mononuclear cells (PBMC). Therefore, it seemed possible that these patients have antibodies to the tax protein. To investigate this, enzyme-linked immunosorbent assays (ELI-SAs) and Western blot assays were set up, using as antigens the full-length HTLV-I tax cloned from the prototypic HTLV-I-infected cell line, C91PL, and from PBMC of a MF patient, as well as a synthetic peptide made to the carboxy-terminal 20 amino acids of tax-I. Of 60 MF patients whose PBMC were shown to be positive for tax proviral DNA and mRNA, 50 (83%) were shown to have tax antibodies. The antigen derived from the MF patient was most useful in detecting such antibodies. These results demonstrate the need for including other HTLV-related antigens in addition to gag and env in serologic tests used to identify HTLV-infected individuals. The findings underscore the fact that individuals considered seronegative on the basis of currently used tests can be infected with HTLV.

  16. Topical Chemotherapy in Cutaneous T-cell Lymphoma: Positive Results of a Randomized, Controlled, Multi-center Trial Testing the Efficacy and Safety of a Novel 0.02% Mechlorethamine Gel in Mycosis Fungoides

    PubMed Central

    Lessin, Stuart R.; Duvic, Madeleine; Guitart, Joan; Pandya, Amit G.; Strober, Bruce E.; Olsen, Elise A.; Hull, Christopher M.; Knobler, Elizabeth H.; Rook, Alain H.; Kim, Ellen J.; Naylor, Mark F.; Adelson, David M.; Kimball, Alexa B.; Wood, Gary S.; Sundram, Uma; Wu, Hong; Kim, Youn H.

    2013-01-01

    Objective Evaluate the efficacy & safety of a novel 0.02% mechlorethamine (MCH) gel in mycosis fungoides (MF). Design Multi-center, randomized, observer-blinded, active controlled trial, comparing 0.02% MCH gel with 0.02% MCH compounded ointment. MCH was applied once daily for up to 12 months. Tumor response and adverse events (AEs) were assessed every month (months 1–6) and every 2 months (months 7–12). Serum drug levels were drawn on a subset of subjects. Setting Academic medical and/or cancer centers Patients 260 Stage IA-IIA MF patients who had not used topical MCH within 2 years and were naïve to prior use of topical carmustine therapy. Main Outcome Measures Response rates (RRs) of all subjects based on primary (composite assessment of index lesion severity - CAILS) and secondary (modified severity weighted assessment tool (mSWAT) and time to response analyses) clinical endpoints. Results RR for MCH gel and ointment were 59% vs. 48% by CAILS and 46.9% vs. 46.2% by mSWAT, respectively. The ratio of CAILS RR of MCH gel to ointment was 1.23 (CI: 0.97–1.55), which met the pre-specified criterion for non-inferiority. Time to response demonstrated superiority of MCH gel to ointment (p<0.012). No drug-related serious AEs were seen. Twenty percent (20%) of enrolled patients on gel and 17% on ointment withdrew due to drug-related skin irritation. No systemic absorption of the study medication was detected. Conclusions These results demonstrate the safety and efficacy of a novel 0.02% MCH gel in the treatment of MF patients. Clinical Trial Registration NCT00168064 PMID:23069814

  17. Oral and Cutaneous Lymphomas other than Mycosis Fungoides and Sézary Syndrome in a Mexican Cohort: Recategorization and Evaluation of International Geographical Disparities

    PubMed Central

    Hernández-Salazar, Amparo; García-Vera, Jorge Andrés; Charli-Joseph, Yann; Ortiz-Pedroza, Guadalupe; Méndez-Flores, Silvia; Orozco-Topete, Rocío; Morales-Leyte, Ana Lilia; Domínguez-Cherit, Judith; Lome-Maldonado, Carmen

    2017-01-01

    Background: Nonmycosis fungoides/Sézary syndrome (non-MF/SS) primary cutaneous lymphomas (PCL) are currently categorized under the 2005-World Health Organization/European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for PCL. These differ in behavior from secondary cutaneous lymphomas (SCL) and to lymphomas limited to the oral cavity (primary oral lymphomas [POL]) both categorized under the 2016-WHO classification for lymphoid neoplasms. Aims: This study aims to report the first series of non-MF/SS PCL, SCL, and POL in a Mexican cohort, examine the applicability of current classification systems and compare our findings with those from foreign cohorts. Materials and Methods: Eighteen non-MF/SS PCL, four SCL, and two POL with available tissue for morphology and immunophenotypic assessment were reclassified according to the 2005-WHO/EORTC and 2016-WHO classifications. Results: Non-MF/SS PCLs were primarily of T-cell origin (61%) where CD30+ lymphoproliferative disorders predominated, followed by Epstein–Barr virus-induced lymphomas, and peripheral T-cell lymphomas, not otherwise specified. Primary cutaneous B-cell lymphomas (BCL) were primarily of follicle center cell origin followed by postgerminal lymphomas of the diffuse large BCL variety. Conclusions: Most non-MF/SS PCL, SCL, and POL can be adequately categorized according to the 2005-WHO/EORTC and 2016-WHO classification systems, even when dealing with clinically atypical cases. The relative frequencies in our cohort hold closer similarities to Asian registries than from those of Europe/USA, supporting the concept of individual and/or racial susceptibility, and the notion of geographical variances in the rate of lymphomas. In particular, such disparity may arise from viral-induced lymphomas which might show partial geographical restriction. PMID:28400635

  18. Cutaneous T cell lymphomas: mycosis fungoides, Sezary syndrome and HTLV-I-associated adult T cell leukemia (ATL) in Mali, West Africa: a clinical, pathological and immunovirological study of 14 cases and a review of the African ATL cases.

    PubMed

    Fouchard, N; Mahe, A; Huerre, M; Fraitag, S; Valensi, F; Macintyre, E; Sanou, F; de The, G; Gessain, A

    1998-04-01

    Cutaneous T cell lymphomas (CTCL) are rare lymphoproliferative diseases, which are frequently suspected to be of viral origin. As very few data were available concerning cutaneous T cell lymphomas in tropical Africa, we undertook a clinical, histopathological, immunological and viro-molecular study of patients with a clinical diagnosis of cutaneous lymphoma, in Bamako, Mali. While prior to this study, no case of CTCL had been reported in this country, 14 patients (five women, nine men; mean age 58 years) with a diagnosis of cutaneous lymphoma were seen over a period of 30 months (1992-1994) in the only dermatological department in Mali. Clinically, the most frequent pattern was an infiltrated erythrodermia similar to Sezary syndrome. Nodular lesions and/or plaques were rarely observed. All these cutaneous tumors were T cell lymphoproliferations, only one expressing the CD8+ antigen. A comprehensive analysis of all the available data permitted characterization of three cases of adult T cell leukemia/lymphoma (ATL) associated with HTLV-I (one definitive case, of leukemic type, with demonstration of clonal integration of HTLV-I proviral genome and two probable ATL cases), three cases of Sezary syndrome (SS), two cases of mycosis fungoides (MF) and five cases of pleomorphic cutaneous lymphoma. In one case, the differentiation between MF and pleomorphic cutaneous lymphoma could not be established. HTLV-I serological and/or molecular markers were restricted to the three ATL cases. From the unique definitive ATL case, a T cell line was established from culture of peripheral blood mononuclear cells and sequence analysis of the env gene and the U3-LTR region demonstrated that the virus present in this patient belonged to the cosmopolitan subtype A. Thus, we report here the first evidence of HTLV-I infection and associated ATL in Mali. This is the second ATL case described for the whole Sahelian region (one ATL of the lymphoma type was reported previously in a Mauritanian

  19. Preliminary discussion on the value of (18)F-FDG PET/CT in the diagnosis and early staging of non-mycosis fungoides/Sézary's syndrome cutaneous malignant lymphomas.

    PubMed

    Dan, Shao; Qiang, Gao; Shu-Xia, Wang; Chang-Hong, Liang

    2015-07-01

    To discuss the value of (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-PET/CT) scans in the diagnosis and early staging of non-mycosis fungoides/Sézary's syndrome cutaneous malignant lymphomas (non-MF/SS CML). A total of 18 cases with non-MF/SS CML, confirmed by pathology or on clinical grounds, were analyzed in this study. The sensitivity of CT and PET/CT scans in the diagnosis of primary skin lesions, as well as the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CT and PET/CT scans in the diagnosis of lymph nodes (LNs) and other organs (except skin and LNs) were calculated. The diagnostic sensitivity of CT and PET/CT scans in the diagnosis of primary skin lesions was 82.4% (14/17) and 100% (17/17), respectively. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CT and PET/CT scans in the diagnosis of LN lesions were 55.6% (5/9), 88.9% (8/9), 72.2% (13/18), 83.3% (5/6), 66.7% (8/12), and 88.9% (8/9), 100% (9/9), 94.4% (17/18), 100% (8/8), 90.0% (9/10), respectively. The diagnostic value of the CT and PET/CT scans in the diagnosis of involvement of other organs, were 40.4% (2/5), 100% (13/13), 83.3 (15/18), 100% (2/2), 81.3% (13/16) and 80.6% (4/5), 100% (13/13), 94.4% (17/18), 100% (3/3), 92.9% (13/14), respectively. (18)F-FDG PET/CT has high value in the diagnosis and early staging of non-MF/SS CMLs. Copyright © 2015. Published by Elsevier Ireland Ltd.

  20. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

    PubMed Central

    Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

    2015-01-01

    Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and

  1. Epidermolysis Bullosa

    MedlinePlus

    ... of the hands and soles of the feet; rough, thickened, or absent fingernails or toenails; and blistering ... and mild forms of junctional epidermolysis bullosa include rough and thickened or absent fingernails and toenails; a ...

  2. Epidermolysis bullosa, dystrophic (image)

    MedlinePlus

    This picture shows skin lesions (epidermolysis bullosa) over the joints on the hands and feet (interphalangeal joints). Dystrophic epidermolysis bullosa is an inherited condition that causes red, blisters ( ...

  3. Clinical End Points and Response Criteria in Mycosis Fungoides and Sézary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer

    PubMed Central

    Olsen, Elise A.; Whittaker, Sean; Kim, Youn H.; Duvic, Madeleine; Prince, H. Miles; Lessin, Stuart R.; Wood, Gary S.; Willemze, Rein; Demierre, Marie-France; Pimpinelli, Nicola; Bernengo, Maria Grazia; Ortiz-Romero, Pablo L.; Bagot, Martine; Estrach, Teresa; Guitart, Joan; Knobler, Robert; Sanches, José Antonio; Iwatsuki, Keiji; Sugaya, Makoto; Dummer, Reinhard; Pittelkow, Mark; Hoppe, Richard; Parker, Sareeta; Geskin, Larisa; Pinter-Brown, Lauren; Girardi, Michael; Burg, Günter; Ranki, Annamari; Vermeer, Maartan; Horwitz, Steven; Heald, Peter; Rosen, Steve; Cerroni, Lorenzo; Dreno, Brigette; Vonderheid, Eric C.

    2011-01-01

    Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS. PMID:21576639

  4. Epidermolysis bullosa, dominant dystrophic (image)

    MedlinePlus

    This picture shows skin lesions (epidermolysis bullosa) over the joints on the hands and feet (interphalangeal joints). Dystrophic epidermolysis bullosa is an inherited condition that causes red blisters ( ...

  5. Treatment Option Overview (Mycosis Fungoides and the Sezary Syndrome)

    MedlinePlus

    ... syndrome are hard to cure . Treatment is usually palliative , to relieve symptoms and improve the quality of ... Sézary syndrome, and may also be used as palliative therapy to relieve symptoms and improve quality of ...

  6. Treatment Options by Stage (Mycosis Fungoides and the Sezary Syndrome)

    MedlinePlus

    ... syndrome are hard to cure . Treatment is usually palliative , to relieve symptoms and improve the quality of ... Sézary syndrome, and may also be used as palliative therapy to relieve symptoms and improve quality of ...

  7. General Information about Mycosis Fungoides and the Sezary Syndrome

    MedlinePlus

    ... syndrome are hard to cure . Treatment is usually palliative , to relieve symptoms and improve the quality of ... Sézary syndrome, and may also be used as palliative therapy to relieve symptoms and improve quality of ...

  8. Treatment Options for Recurrent Mycosis Fungoides and the Sezary Syndrome

    MedlinePlus

    ... syndrome are hard to cure . Treatment is usually palliative , to relieve symptoms and improve the quality of ... Sézary syndrome, and may also be used as palliative therapy to relieve symptoms and improve quality of ...

  9. Stages of Mycosis Fungoides and the Sezary Syndrome

    MedlinePlus

    ... syndrome are hard to cure . Treatment is usually palliative , to relieve symptoms and improve the quality of ... Sézary syndrome, and may also be used as palliative therapy to relieve symptoms and improve quality of ...

  10. Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a dog.

    PubMed

    Bhang, Dong Ha; Choi, Ul Soo; Kim, Min Kyu; Choi, Eun-Hwa; Kang, Min-Soo; Hwang, Cheol-Yong; Kim, Dae-Yong; Youn, Hwa Young; Lee, Chang Woo

    2006-03-01

    A seven-year-old castrated male Yorkshire terrier dog was presented for a recurrent skin disease. Erythematous skin during the first visit progressed from multiple plaques to patch lesions and exudative erosion in the oral mucosa membrane. Biopsy samples were taken from erythematous skin and were diagnosed with epitheliotropic T cell cutaneous lymphoma by histopathology and immunochemical stain. In serum chemistry, the dog had a hypercalcemia (15.7 mg/dl) and mild increased alkaline phosphatase (417 U/l). Immunohistochemistry was performed to detect parathyroid hormone-related peptide (PTH-rP) in epitheliotropic cutaneous lymphoma tissues but the neoplastic cells were not labeled with anti-PTH-rP antibodies. The patient was treated with prednisolone and isotretinoin. However, the dog died unexpectedly.

  11. Ichthyosis bullosa of Siemens.

    PubMed

    Ang-Tiu, Charlene U; Nicolas, Marie Eleanore O

    2012-09-28

    Ichthyosis bullosa of Siemens (IBS) is a rare hyperkeratotic blistering condition caused by mutations in keratin 2e gene. This is a case of a 18-year-old female with generalized blisters, erosions and thickened skin since she was 3 months old. As she aged, there was decrease in development of blisters and erosions, with accompanying increase in severity of hyperkeratosis. Skin punch biopsy showed overlying basket weave hyperkeratosis and acanthosis, prominent vacuolization of the granular cell layer, and intraepidermal blisters with the split at the granular layer. The patient was treated with emollients, with marked improvement. Mutations in the different keratin genes have been shown to underlie a wide range of disorders of keratinization. Epidermolytic hyperkeratosis and ichthyosis bullosa of Siemens are distinct disorders with mutations in different genes. Although molecular genetic testing should ideally be done for confirmation of diagnosis, ichthyosis bullosa of Siemens could be diagnosed in this patients based on key clinical characteristics.

  12. Genetics Home Reference: dystrophic epidermolysis bullosa

    MedlinePlus

    ... Twitter Home Health Conditions dystrophic epidermolysis bullosa dystrophic epidermolysis bullosa Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Epidermolysis bullosa is a group of genetic conditions that cause ...

  13. Genetics Home Reference: epidermolysis bullosa simplex

    MedlinePlus

    ... Facebook Twitter Home Health Conditions epidermolysis bullosa simplex epidermolysis bullosa simplex Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Epidermolysis bullosa simplex is one of a group of genetic ...

  14. What Is Epidermolysis Bullosa?

    MedlinePlus

    ... publication. To order the Epidermolysis Bullosa Q&A full-text version, please contact NIAMS using the contact information above. To view the complete text or to order online, visit www.niams.nih.gov . Many of ... NIAMS Site NIH… Turning Discovery Into Health ® Home | ...

  15. Angina bullosa hemorrhagica.

    PubMed

    de las Heras, M E; Moreno, R; Núñez, M; Gómez, M I; Ledo, A

    1996-07-01

    Angina bullosa hemorrhagica is characterized by acute blood blisters, mainly on the soft palate. Elderly patients are usually affected and lesions heal spontaneously without scarring. The pathogenesis is unknown, although it may be a multifactorial phenomenon. Trauma seems to be the major provoking factor and long term use of steroid inhalers has also been implicated in the disease. No underlying hematologic or immunopathogenic disorder has been found. Treatment is symptomatic. We present a 67-year-old patient with recurrent oral blood blisters which were diagnosed as angina bullosa hemorrhagica. Trauma by dental injections and use of steroid inhalers were identified as etiologic factors in this case. Erosions healed with a week. Although this is a benign condition, it may result in acute airway obstruction. Recognition is, therefore, of great importance for dermatologists.

  16. Angina bullosa haemorrhagica

    PubMed Central

    Singh, Dipti; Misra, Neeta; Agrawal, Sudhanshu; Misra, Pradyumna

    2013-01-01

    Angina bullosa haemorrhagica is the term used to describe benign subepithelial oral mucosal blisters filled with blood that are not attributable to a systemic disorder or haemostatic defect. It is a very rare condition. Elderly patients are usually affected and lesions heal spontaneously without scarring. The pathogenesis is unknown, although it may be a multifactorial phenomenon. Trauma seems to be the major provoking factor and long-term use of steroid inhalers has also been implicated in the disease. We present a 50-year-old patient with angina bullosa haemorrhagica. Trauma by sharp cusp of adjacent tooth and metal crown were identified as aetiological factors in this case. Lesions healed after removal of the metal crown and rounding of the cusp. Therefore, recognition of the lesion is of great importance to dentists, to avoid misdiagnosis. PMID:23396938

  17. Angina bullosa haemorrhagica

    PubMed Central

    Shoor, Hitesh; Mutalik, Sunil; Pai, Keerthilatha M

    2013-01-01

    A woman in her early 40s presented with a painless ulceration on the right side of the posterior palate, she had an earlier history of similar lesions after the rupturing of blood filled blisters in the oral cavity. On examination, a diffuse erythematous area and ulcers covered with necrotic slough were noticed on the right and left side of the posterior palate and on the right buccal mucosa. On follow-up visit, a large blood filled blister was noticed in the buccal vestibule. We advised routine haematological investigations to rule out any bleeding disorders and direct immunofluorescence of the affected tissue and perilesional areas to rule out autoimmune blistering conditions. Haematological investigations revealed no abnormalities and immunofluorescence testing was negative. A diagnosis of angina bullosa haemorrhagica was made by excluding all other conditions. Symptomatic treatment was given, patient was educated about the condition and reassured. PMID:24334011

  18. Dental considerations in hereditary epidermolysis bullosa.

    PubMed

    Sharma, S Mahesh; Mohan, Muralee; Baptist, Joanna

    2014-01-01

    Epidermolysis bullosa is an inherited mucocutaneous disorder characterized by blister formation due to a defect in collagen metabolism. Each of the three major subtypes of epidermolysis bullosa has distinct clinical and oral manifestations. A case report of the most classic form of epidermolysis bullosa, recessive dystrophic epidermolysis bullosa, is presented here, along with a review of the literature on the clinical features and management of the condition. An attempt has been made to highlight the anesthetic and oral surgical considerations when treating a patient with epidermolysis bullosa.

  19. Management of manifestations of epidermolysis bullosa.

    PubMed

    Elluru, Ravindhra G; Contreras, Jose M; Albert, David M

    2013-12-01

    Children with epidermolysis bullosa can present with disease(s) of the ears, nose, and throat, often related directly to the pathophysiology of their epidermolysis bullosa. Otolaryngologic diseases in children with epidermolysis bullosa have to be managed having a proper understanding of the diagnosis and pathophysiology of epidermolysis bullosa. The purpose of this review is to describe the current nomenclature and diagnostic algorithms for epidermolysis bullosa, and methods for the management of cutaneous and mucosal lesions. Characterization of the gene defects leading to epidermolysis bullosa has allowed the utilization of immunofluorescent techniques as the primary method for epidermolysis bullosa diagnosis. Recognizing the difficulty in managing patients with epidermolysis bullosa, several multidisciplinary groups have developed guidelines using meta-analysis of the published literature, or expert panels. Though there are currently no effective treatment modalities for epidermolysis bullosa, techniques for gene and protein replacement show promising results for future use. Currently, the management of cutaneous and mucosal disease in epidermolysis bullosa is based on the principles of prevention and wound care. Understanding the cause of epidermolysis bullosa types and subtypes, characteristics of skin and mucosal involvement, and prognosis will guide in the development of individualized treatment plans.

  20. Genetics Home Reference: epidermolysis bullosa with pyloric atresia

    MedlinePlus

    ... Home Health Conditions epidermolysis bullosa with pyloric atresia epidermolysis bullosa with pyloric atresia Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Epidermolysis bullosa with pyloric atresia (EB-PA) is a condition ...

  1. Inherited epidermolysis bullosa

    PubMed Central

    2010-01-01

    Inherited epidermolysis bullosa (EB) encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues. All types and subtypes of EB are rare; the overall incidence and prevalence of the disease within the United States is approximately 19 per one million live births and 8 per one million population, respectively. Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs. Each EB subtype is known to arise from mutations within the genes encoding for several different proteins, each of which is intimately involved in the maintenance of keratinocyte structural stability or adhesion of the keratinocyte to the underlying dermis. EB is best diagnosed and subclassified by the collective findings obtained via detailed personal and family history, in concert with the results of immunofluorescence antigenic mapping, transmission electron microscopy, and in some cases, by DNA analysis. Optimal patient management requires a multidisciplinary approach, and revolves around the protection of susceptible tissues against trauma, use of sophisticated wound care dressings, aggressive nutritional support, and early medical or surgical interventions to correct whenever possible the extracutaneous complications. Prognosis varies considerably and is based on both EB subtype and the overall health of the patient. PMID:20507631

  2. 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

  3. Podiatric management in epidermolysis bullosa.

    PubMed

    Khan, M Tariq

    2010-04-01

    Epidermolysis bullosa (EB) results from genetic defects of molecules in the skin concerned with adhesion. Some of the most common problems seen with EB sufferers are blisters, vesicles, and bullas. Maintaining foot cleanliness, exercising, and wearing shoes are all good preventative measures and important in EB foot care.

  4. Stem-cell Based Therapies for Epidermolysis Bullosa

    DTIC Science & Technology

    2013-10-01

    Epidermolysis Bullosa PRINCIPAL INVESTIGATOR: Dennis Roop, Ph.D. CONTRACTING ORGANIZATION...5a. CONTRACT NUMBER Stem-cell Based Therapies for Epidermolysis Bullosa 5b. GRANT NUMBER W81XWH-12-1-0606 5c. PROGRAM ELEMENT NUMBER 6... Bullosa , and proposes to develop stem-cell based therapies for junctional epidermolysis bullosa (JEB), which is one of the most severe forms of

  5. Advancement in management of epidermolysis bullosa.

    PubMed

    Cohn, Heather I; Teng, Joyce M C

    2016-08-01

    Epidermolysis bullosa is a hereditary skin disorder characterized by skin fragility. However, the disease can manifest in many different organ systems, therefore children born with epidermolysis bullosa may have life long, complex medical needs. In this review, we will use a system-based approach to highlight important aspects of disease management and recent advancements in each of the areas. In addition, we will overview some of the cutting edge therapeutic developments in epidermolysis bullosa. Recent advancements in supportive care of epidermolysis bullosa with focus on wound, pain, pruritus and nutrition status were discussed. Clinical surveillance and complication prevention are critical to improve clinical outcomes. Generalized epidermolysis bullosa is a systemic disease with increased morbidity and mortality; therefore, complex care using a multidisciplinary approach will provide the greatest benefits for patients. Current targeted treatments for epidermolysis bullosa aim at restoring the skin integrity using protein, cell, and gene therapies. Improvement in care of epidermolysis bullosa in recent years results from keen clinical observation, novel molecular targeting, and the embracement of translational research.

  6. Reduced Intensity Conditioning Before Partially Matched Donor Stem Cell Transplant in Treating Patients With Advanced Cutaneous T Cell Lymphoma

    ClinicalTrials.gov

    2016-10-19

    Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Stage IIB Mycosis Fungoides and Sezary Syndrome; Stage IIIA Mycosis Fungoides and Sezary Syndrome; Stage IIIB Mycosis Fungoides and Sezary Syndrome; Stage IVA Mycosis Fungoides and Sezary Syndrome; Stage IVB Mycosis Fungoides and Sezary Syndrome

  7. Massive concha bullosa pyocele with orbital extention.

    PubMed

    Bahadir, Osman; Imamoglu, Mehmet; Bektas, Devrim

    2006-06-01

    Concha bullosa is the most common anatomic variant of the middle turbinate. It remains usually asymptomatic. Pyocele occurs when concha bullosa becomes infected. In the formation of a pyocele, middle turbinate may become expanded and occupy the surrounding structures with local bone destruction. Direct extension of mass from the nose into the orbit may occur, because the orbital contents are separated from the ethmoidal labyrinth only by the thin lamina papyracea. We report a case of concha bullosa pyocele with orbital extension. Orbital involvement is also associated with ocular functional loss. In this case, ocular motion and vision remained normal despite of the presence of orbital extension for 2 years.

  8. Epidermolysis bullosa care in Mexico.

    PubMed

    Liy-Wong, Carmen; Cepeda-Valdes, Rodrigo; Salas-Alanis, Julio Cesar

    2010-04-01

    Epidermolysis bullosa (EB) in Mexico continues to be a rare genodermatosis that is still unknown for most of the health care professionals in the country. The spirit of DebRA MEXICO was born in 1994 when the Mexican health care team started to see patients with the main purpose to provide medical care, genetic counseling, and advice to patients with EB and their families; to promote collaboration and exchange information among people with EB; to research and find new therapeutic approaches; and finally, to diffuse knowledge and raise awareness of the issues of EB in general public and health care professionals.

  9. Dystrophic epidermolysis bullosa: a review

    PubMed Central

    Shinkuma, Satoru

    2015-01-01

    Dystrophic epidermolysis bullosa is a rare inherited blistering disorder caused by mutations in the COL7A1 gene encoding type VII collagen. The deficiency and/or dysfunction of type VII collagen leads to subepidermal blistering immediately below the lamina densa, resulting in mucocutaneous fragility and disease complications such as intractable ulcers, extensive scarring, malnutrition, and malignancy. The disease is usually diagnosed by immunofluorescence mapping and/or transmission electron microscopy and subsequently subclassified into one of 14 subtypes. This review provides practical knowledge on the disease, including new therapeutic strategies. PMID:26064063

  10. Pulmonary mycobacteriosis in a patient affected by mycosis fungoides: a diagnostic and therapeutic challenge.

    PubMed

    Borroni, R G; Bottoni, U; Devirgiliis, V; Panasiti, V; Mancini, M; Curzio, M; Rossi, M; Venditti, M; Martelli, M; Delia, S; Clerico, R; Calvieri, S

    2006-10-01

    Among patients with cutaneous T-cell lymphoma (CTCL), sepsis and pulmonary infections are the first cause of death. We report on a patient with CTCL who, after more than 10 years of aggressive antineoplastic treatments, showed extensive pulmonary infiltrations on staging CT scan. Repeated CT scans were inconclusive for an infectious process, and the patient was still asymptomatic. The diagnosis of mycobacteriosis was made on the microbiologic exam of bronchoalveolar lavage. Specific treatment was started with contemporary dosage reduction of chemotherapy. After six months of antibiotic treatment the pulmonary lesions improved, whereas CTCL progressed. Therefore, a new antineoplastic regimen was started obtaining control of CTCL, without aggravation of the pulmonary lesions. We highlight the diagnostic and therapeutic pitfalls encountered when pulmonary mycobacteriosis complicates the course and treatment of CTCL.

  11. Genetics Home Reference: junctional epidermolysis bullosa

    MedlinePlus

    ... type XVII collagen. Collagens are molecules that give structure and strength to connective tissues, such as skin, ... Mutation analysis and molecular genetics of epidermolysis bullosa. Matrix Biol. 1999 Feb;18(1):29-42. Review. ...

  12. Epidermolysis bullosa in animals: a review.

    PubMed

    Medeiros, Gildenor X; Riet-Correa, Franklin

    2015-02-01

    Epidermolysis bullosa (EB) is a hereditary mechanobullous disease of animals and humans, characterized by an extreme fragility of the skin and mucous membranes. The main feature of EB in humans and animals is the formation of blisters and erosions in response to minor mechanical trauma. Epidermolysis bullosa is caused by mutations in the genes that code for structural proteins of the cytoskeleton of the basal keratinocytes or of the basement membrane zone. Based on the ultrastructural levels of tissue separation, EB is divided into the following three broad categories: epidermolysis bullosa simplex, junctional epidermolysis bullosa and dystrophic epidermolysis bullosa. Human types of EB are divided into several subtypes based on their ultrastructural changes and the mode of inheritance; subtypes are not fully established in animals. In humans, it is estimated that EB affects one in 17,000 live births; the frequency of EB in different animals species is not known. In all animal species, except in buffalo with epidermolysis bullosa simplex, multifocal ulcers are observed on the gums, hard and soft palates, mucosa of the lips, cheek mucosa and dorsum of the tongue. Dystrophic or absent nails, a frequent sign seen in human patients with EB, corresponds to the deformities and sloughing of the hooves in ungulates and to dystrophy or atrophy of the claws in dogs and cats. This review covers aspects of the molecular biology, diagnosis, classification, clinical signs and pathology of EB reported in animals. © 2014 ESVD and ACVD.

  13. Natural gene therapy in dystrophic epidermolysis bullosa.

    PubMed

    van den Akker, Peter C; Nijenhuis, Miranda; Meijer, Gonnie; Hofstra, Robert M W; Jonkman, Marcel F; Pasmooij, Anna M G

    2012-02-01

    Dystrophic epidermolysis bullosa is a genetic blistering disorder caused by mutations in the type VII collagen gene, COL7A1. In revertant mosaicism, germline mutations are corrected by somatic events resulting in a mosaic disease distribution. This "natural gene therapy" phenomenon long has been recognized in other forms of epidermolysis bullosa but only recently in dystrophic epidermolysis bullosa. We describe a 21-year-old man with recessive dystrophic epidermolysis bullosa carrying the homozygous c.6508C>T (p.Gln2170X) nonsense mutation who reported an unaffected skin patch on his neck where blisters never had occurred. Immunofluorescent type VII collagen staining was normal in 80% of the unaffected skin biopsy; however, it was strongly reduced in the affected skin. In the unaffected skin, the somatic nucleotide substitution c.6510G>T reverted the germline nonsense codon to tyrosine (p.Gln2170Tyr), thereby restoring functional protein production. Revertant mosaicism is considered rare in recessive dystrophic epidermolysis bullosa. However, it might be more common than previously anticipated because our patient is the third in whom revertant mosaicism was identified in a short period of time. The correction mechanism is different than that previously reported. Systematic examination of patients with recessive dystrophic epidermolysis bullosa, therefore, will likely reveal more patients with revertant patches. This is important because the natural gene therapy phenomenon may provide opportunities for revertant cell therapy.

  14. Use of Epidermolysis Bullosa Biomarkers in Models of Vesicant Injury

    DTIC Science & Technology

    2006-09-01

    AD_________________ Award Number: DAMD17-02-C-0091 TITLE: Use of Epidermolysis Bullosa ...Final 3. DATES COVERED (From - To) 15 May 2002 – 31 Aug 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Use of Epidermolysis Bullosa Biomarkers...page 15. SUBJECT TERMS Epidermolysis Bullosa Biomarkers Vesicant Injury 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER

  15. Treatment of feet deformities in epidermolysis bullosa.

    PubMed

    Sternick, Marcelo Back; Formentini, Pierina Kaneno Ishida; de Souza, Gustavo Moreira Costa; Teixeira, Eduardo Cembranelli; de Almeida Filho, Ildeu Afonso; da Costa, Sérgio Moreira

    2016-07-01

    Inherited epidermolysis bullosa is a rare disease characterised by mechanical fragility of the skin when under insignificant stress. The main consequences of epidermolysis bullosa, mainly the dystrophic type, despite pseudosyndactyly, are joint contractures and deformities in hands and feet. In this study, we describe our experience treating patients suffering from epidermolysis bullosa, as far as feet deformities are concerned. This is a retrospective analysis of a consecutive series of patients presenting feet deformities related to epidermolysis bullosa. Extension contractures of the toes, equinus and cavus deformities were treated with soft tissues surgery. Thirteen surgical procedures were done in six patients with feet deformities caused by epidermolysis bullosa. Of the feet operated 85.7 % extension contracture of the toes was asymptomatic at follow-up. However, 42.9 % developed hammertoe deformities. There were no recurrence or complications for other deformities. Subjectively, all patients declared themselves very satisfied with the results. Foot deformities must be treated as early as possible, due to progressive disability for walking and pain symptoms. We considered that, despite long term complications, treatment was adequate and we recommend it. Level of Evidence Level IV.

  16. Anesthetic consideration in dystrophic epidermolysis bullosa.

    PubMed

    Narejo, A S; Khan, M U; Alotaibi, W M; Khan, M M

    2016-01-01

    Epidermolysis bullosa is a group of inherited rare skin disease, characterized by bullae formation in the skin or mucous membranes. The fundamental abnormality is collagen degeneration leads to splitting of various epidermal layers. Dystrophic epidermolysis bullosa (DEB) is one of the major forms of epidermolysis bullosa. These patients often admitted to the hospital for corrective surgeries, change of dressing, contracture release, and skin grafting. Anesthetic management of these cases is always a challenge. We are reporting a case of 5-year-old boy diagnosed as a case of DEB scheduled for upper lip contracture release, skin grafting and debridement of nonhealing scars under anesthesia. In this case, we have focused mainly on the anesthetic management, preparation of the monitoring, transportation, difficulties in establishing the venous accesses, and airway management.

  17. Host defence to pulmonary mycosis

    PubMed Central

    Mody, Christopher H; Warren, Peter W

    1999-01-01

    OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease. DATA SOURCES: English articles from 1966 to present were identified from a MEDLINE search. STUDY SELECTION: Articles were identified by a MEDLINE search of ‘exp lung/’ or ‘exp lung diseases/’ and ‘exp fungi/’. The titles and abstracts were screened to identify articles that contained salient information pertaining to host defense of respiratory mycoses. DATA EXTRACTION: Information was summarized from the articles pertaining to host defense of pulmonary mycosis that had been identified by the MEDLINE search. DATA SYNTHESIS: Fungi represent a unique and highly diverse group of pathogenic organisms that have become an increasingly prevalent cause of life-threatening illness. A worldwide increase in persons with immunodeficiency has been a major contributing factor to the increase in fungal disease. As a result, clinicians are faced with an expanding array of fungal infections that pose diagnostic and therapeutic challenges. The respiratory tract is the route of acquisition for many important fungal infections; thus, understanding the host defense in the lung is an essential component of understanding host defense to fungal disease. With this understanding, fungi may be divided on the basis of the predilection of certain mycosis for specific immune defects. CONCLUSIONS: By separating fungi based on the host immune defects that predispose to disease, in conjunction with traditional divisions based on the geographic distribution of fungi, clinicians are able to focus their diagnostic efforts and to identify fungal pathogens better. In addition, an understanding of the normal host defense mechanisms that serve to control fungal infections is essential to the development of novel antifungal

  18. Life, epidermolysis bullosa and chasing tornadoes.

    PubMed

    Hall, Sam

    2004-11-01

    Sam Hall was diagnosed with epidermolysis bullosa as a baby. Here she describes growing up with the condition and the continual dressing changes it brings, and how she has not let it prevent her from leading an active and exciting life.

  19. Use of Epidermolysis Bullosa Biomarkers in Models of Vesicant Injury

    DTIC Science & Technology

    2005-06-01

    AD Award Number: DAMDI7-02-C-0091 TITLE: Use of Epidermolysis Bullosa Biomarkers in Models of Vesicant Injury PRINCIPAL INVESTIGATOR: Donald R...NUMBERS Use of Epidermolysis Bullosa Biomarkers in Models of DAMDI7-02-C-0091 Vesicant Injury 6. A UTHOR(S) Donald R. Gerecke, Ph.D. Carol L. Sabourin...induced skin injury and the skin disease Epidermolysis Bullosa (EB) in both the morphology of the damage and the structural components involved. Both HD

  20. Stem-cell Based Therapies for Epidermolysis Bullosa

    DTIC Science & Technology

    2013-10-01

    Epidermolysis Bullosa PRINCIPAL INVESTIGATOR: Dennis Roop, PhD (Initiating PI) Jakub Tolar, MD, PhD...30 Sep 2012 – 29 Sep 2013 4. TITLE AND SUBTITLE Stem-cell Based Therapies for Epidermolysis Bullosa 5a. CONTRACT NUMBER 5b. GRANT NUMBER...SUPPLEMENTARY NOTES 14. ABSTRACT This application addresses the FY11 PRMRP Topic Area, Epidermolysis Bullosa , and proposes to develop stem- cell based

  1. Dose-Escalation Trial of Carfilzomib With and Without Romidepsin in Cutaneous T-Cell Lymphoma

    ClinicalTrials.gov

    2015-11-10

    Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome

  2. Epidermolysis bullosa: where do we stand?

    PubMed

    Sarkar, Rashmi; Bansal, Shuchi; Garg, Vijay Kumar

    2011-01-01

    Epidermolysis bullosa, a genetically determined skin fragility disorder can severely incapacitate the life of the afflicted patient. Although the clinical features are multiple and varied, treatment still remains a major challenge. There have been major changes in the classification of the disease recently. Although there is still a long way to go, good nursing care, and gene therapy could possibly significantly alleviate the suffering of the patients in the future.

  3. Angina bullosa hemorrhagica: report of 4 cases.

    PubMed

    Martini, M Zillo; Lemos, C A; Shinohara, E Hitoshi

    2010-03-01

    Angina bullosa hemorrhagica is characterized by the sudden appearance of solitary or multiple hemorrhagic blisters on oral mucosa, with diameters ranging from 2 mm to 3 cm. The soft palate is most commonly affected, but angina bullosa hemorrhagica may also appear on the buccal mucosa, lips and tongue border. Clinically, the blisters have a dark red to purple appearance, and may or may not be painful. The blisters usually break, releasing bloody content and leaving an ulcer surface that heals within 7 to 10 days. In this article the authors describe four cases of angina bullosa hemorrhagica attended in Stomatology Department of Dental School, Sao Paulo State University. In case 1, a 29-year-old male presented with a sudden hemorrhagic blister on the soft palate. A drainage was performed and after seven days of follow-up the patient reported no symptoms. In case 2, a 63-year-old male presented complaining of a blister on the palate six days earlier that had spontaneously broken. General exam showed hypertension under medical control. An incisional biopsy was performed and after seven days follow-up the healing was completed. In case 3, a 61-year-old male arrived complaining of a sudden appearance of an hemorrhagic blister on the soft palate that had spontaneously broken. The patient had systemic hypertension under medical control. The ulcer healed in 10 days follow-up. In case 4, a 49-year-old woman presented complaining of pain and an ulcer on the soft palate. The patient reported the rapid onset of a blood blister during a meal that broke in few minutes. The resolution occurred after 14 days. Angina bullosa hemorrhagica seems to be more common than reported in the literature and knowledge of the condition is important to right diagnosis and approach when necessary.

  4. Epidermolysis bullosa pruriginosa triggered by scabies infestation.

    PubMed

    Kim, Jaehwan; Loh, Chee Hoou; Murrell, Dedee F

    2013-07-01

    Epidermolysis bullosa pruriginosa (EB-Pr) is an unusual variant of dystrophic EB. Potential genetic disease modifiers and metabolic factors have been investigated, but thus far no specific insight into this phenotype has emerged. We report an in-depth description of three patients diagnosed as having EB-Pr in whom this particular phenotype developed after scabies infestation and dramatically improved after full treatment. This short communication suggests that scabies infestation could be one of the important triggering factors for the development of the EB-Pr phenotype. © 2013 Japanese Dermatological Association.

  5. Inherited epidermolysis bullosa: clinical and therapeutic aspects*

    PubMed Central

    Boeira, Vanessa Lys Simas Yamakawa; Souza, Erica Sales; Rocha, Bruno de Oliveira; Oliveira, Pedro Dantas; de Oliveira, Maria de Fátima Santos Paim; Rêgo, Vitória Regina Pedreira de Almeida; Follador, Ivonise

    2013-01-01

    Inherited epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders that present with skin and, in some cases, mucosal fragility, predisposing patients to the development of blisters and/or erosions after minimal trauma or friction. Children with a recurrent history of these kinds of lesions or neonates that present them in the absence of another reasonable explanation should be investigated. Diagnosis must be based on clinical and histopathological findings. To date, management of inherited EB basically consists in avoiding traumas that trigger lesions, as well as preventing infection and facilitating healing of the wounds with the systematic use of bandages. PMID:23739692

  6. Angina bullosa hemorrhagica: report of two cases.

    PubMed

    Rai, Shalu; Kaur, Mandeep; Goel, Sumit

    2012-11-01

    Angina bullosa hemorrhagic (ABH) describes the acute and sometimes painful onset of oral blood-filled vesicles and bullae, not attributable to blood dyscrasia, vesiculobullous disorders, systemic diseases or other known causes. The haemorrhagic bullae spontaneously burst after a short time resulting in ragged, often painless, superficial erosions that heal spontaneously within 1 week without scarring. Trauma appears to be the most common identifiable precipitating factor, but the essential tissue defect is yet unidentified. This paper presents two cases of ABH with the aim to create awareness regarding occurrence of this lesion, thus avoiding any misdiagnosis.

  7. Angina Bullosa Hemorrhagica: Report of Two Cases

    PubMed Central

    Rai, Shalu; Kaur, Mandeep; Goel, Sumit

    2012-01-01

    Angina bullosa hemorrhagic (ABH) describes the acute and sometimes painful onset of oral blood-filled vesicles and bullae, not attributable to blood dyscrasia, vesiculobullous disorders, systemic diseases or other known causes. The haemorrhagic bullae spontaneously burst after a short time resulting in ragged, often painless, superficial erosions that heal spontaneously within 1 week without scarring. Trauma appears to be the most common identifiable precipitating factor, but the essential tissue defect is yet unidentified. This paper presents two cases of ABH with the aim to create awareness regarding occurrence of this lesion, thus avoiding any misdiagnosis. PMID:23248380

  8. Devastating penile mycosis leading to penile gangrene.

    PubMed

    Hombalkar, N N; Vaze, Dhananjay; Guha, Poonam; Dhandore, Priya D; Gurav, Prakash D

    2013-09-01

    Infective penile gangrene is a rare but known complication of circumcision. The causes may vary from neutropenia, diabetes mellitus, and human immunodeficiency virus infection to lymphoproliferative malignancy. Penile mycosis leading to penile gangrene is a rare entity. Only 1 case has been reported in an adult. Juvenile diabetes mellitus is a peculiar predisposing factor for mycotic infections. We report a case of mycotic penile gangrene in a diabetic child to highlight its potentially preventable disastrous outcome.

  9. Dermal eosinophilic infiltrate in junctional epidermolysis bullosa.

    PubMed

    Saraiya, Ami; Yang, Catherine S; Kim, Jinah; Bercovitch, Lionel; Robinson-Bostom, Leslie; Telang, Gladys

    2015-08-01

    Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by a split in the lamina lucida usually because of mutations in LAMA3, LAMB3 and LAMC2 resulting in absence or reduction of laminin-332. Rare subtypes of JEB have mutations in COL17A1, ITGB4, ITGA6 and ITGA3 leading to reduction or dysfunction of collagen XVII, integrin α6β4 and integrin α3. The classic finding under light microscopy is a paucicellular, subepidermal split. We describe the unusual presence of an eosinophilic infiltrate in the bullae and subjacent dermis in a neonate with JEB, generalized intermediate (formerly known as non-Herlitz-type JEB), discuss the histologic differential diagnosis for a subepidermal blister in a neonate, review the literature regarding cases of epidermolysis bullosa (EB) presenting with inflammatory infiltrates, and discuss mechanisms to explain these findings. This case highlights that eosinophils can rarely be seen in EB and should not mislead the dermatopathologist into diagnosing an autoimmune blistering disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. A concha bullosa crusher for use in endoscopic sinus surgery.

    PubMed

    Woolford, T J; Jones, N S

    2000-03-01

    A concha bullosa may require surgical reduction to facilitate access to the middle meatus during endoscopic sinus surgery. Here we describe an original instrument which enables this procedure to be performed simply with minimal mucosal damage.

  11. Epidermolysis Bullosa with Hypertrophic Pyloric Stenosis in a Newborn.

    PubMed

    Ben Dhaou, Mahdi; Ammar, Saloua; Louati, Hamdi; Zitouni, Hayet; Jallouli, Mohamed; Mhiri, Riadh

    2015-01-01

    Epidermolysis bullosa (EB) is an inherited blistering disorder characterized by the fragility of the skin and mucous membranes. Extracutaneous manifestations can be associated. We report a unique concomitant occurrence of EB and hypertrophic pyloric stenosis in a newborn.

  12. Epidermolysis Bullosa with Hypertrophic Pyloric Stenosis in a Newborn

    PubMed Central

    Ben Dhaou, Mahdi; Ammar, Saloua; Louati, Hamdi; Zitouni, Hayet; Jallouli, Mohamed; Mhiri, Riadh

    2015-01-01

    Epidermolysis bullosa (EB) is an inherited blistering disorder characterized by the fragility of the skin and mucous membranes. Extracutaneous manifestations can be associated. We report a unique concomitant occurrence of EB and hypertrophic pyloric stenosis in a newborn. PMID:26500857

  13. Metaplastic Conditions in The Bladder in Patient with Epidermolysis Bullosa.

    PubMed

    Yilmaz, Kenan; Demirci, Deniz; Baydilli, Numan; Nazlim, Sinan

    2016-01-01

    Epidermolysis bullosa is a rare inherited muco-cutaneous disorder that sometimes presentes with genitourinary involvement. Herein we report the case of an 11-year-old girl with a history of junctional epidermolysis bullosa who was admitted with urological symptoms. On cystoscopy, suspected bullous bladder lesions were observed. Mesonephroid, intestinal and squamous metaplasia is reported here for the first time. Copyright© by the International Brazilian Journal of Urology.

  14. Fungus Ball in Concha Bullosa: A Rare Case with Anosmia

    PubMed Central

    Özkırıs, Mahmut; Kapusuz, Zeliha; Seçkın, Selda; Saydam, Levent

    2013-01-01

    Concha bullosa is the pneumatization of the concha and is one of the most common variations of the sinonasal anatomy. The histopathological changes caused by the infections which arise from the impaired aeration of conchal cavity are frequently found. Fungus ball of the nasal cavity is an extremely rare, fungal infection with only three cases reported previously. In this paper, we present the fourth fungus ball case which developed within a concha bullosa and presented with anosmia. PMID:23936708

  15. Photodynamic effects on T-cells and skin lesions of a patient with mycosis fungoides using porphyrin photosensitizers

    NASA Astrophysics Data System (ADS)

    Koenig, Karsten; Boehncke, Wolf-Henning; Rueck, Angelika C.; Kaufmann, Roland; Steiner, Rudolf W.; Sterry, Wolfram

    1994-02-01

    PUVA is a well established phototreatment modality for various dermatoses, like T cell lymphomas, using long-wavelength UV radiation. In contrast, PDT bases on the combination of photosensitizers, especially porphyrins, and radiation mainly in the red spectral region. We analyzed the photochemical effects of both treatments on cell lines MyLa and HuT78, established from patients with cutaneous T cell lymphomas. Our observations document the capability of PDT to inhibit proliferation of transformed T cells similar to PUVA thus pointing out its potential in the treatment of cutaneous T cell lymphomas.

  16. Cutaneous lymphocyte antigen expression loss and PD1 positivity in early cutaneous lesions of rapidly progressive mycosis fungoides

    PubMed Central

    Ogunrinade, Olakunle; Ahn, Christine S; Gergis, Usama; Yassin, Aminah H; Magro, Cynthia

    2014-01-01

    Key Clinical Message It's important to assess cases both clinically and pathologically for factors potentially predictive of an aggressive clinical course. We concluded that the relative immunosuppressive effects of PD1 may contribute to tumor progression while the lack of staining for cutaneous lymphocyte antigen may be an additional factor facilitating distant extracutaneous migration. PMID:25614814

  17. Distinguishing Epidermolysis Bullosa Acquisita From Bullous Pemphigoid Without Direct Immunofluorescence.

    PubMed

    Gardner, Kerry M; Crawford, Richard I

    2017-07-01

    It has been postulated that periodic acid-Schiff staining of basement membrane can predict direct immunofluorescence patterns seen in epidermolysis bullosa acquisita and bullous pemphigoid. It has also been suggested that the type of inflammatory infiltrate or presence of fraying of basal keratinocytes may differentiate these two conditions. In this study, we aimed to confirm these observations. We reviewed 13 cases of direct immunofluorescence-confirmed epidermolysis bullosa acquisita and 19 cases of direct immunofluorescence-confirmed bullous pemphigoid, all with a subepidermal blister in the routinely processed specimen. The gold standard for diagnosis of epidermolysis bullosa acquisita vs bullous pemphigoid was taken to be identification of immune deposits on the dermal side ('floor' for epidermolysis bullosa acquisita) or the epidermal side ('roof' for bullous pemphigoid) of the salt-split direct immunofluorescence specimen. Our tests to distinguish epidermolysis bullosa acquisita from bullous pemphigoid on the routinely processed biopsy included periodic acid-Schiff basement membrane on the blister roof, neutrophilic infiltrate, lack of eosinophilic infiltrate, and absence of keratinocyte fraying. Sensitivity and specificity for each test were as follows: periodic acid-Schiff staining of roof (sensitivity 25%, specificity 95%), neutrophilic infiltrate (sensitivity 54%, specificity 74%), lack of eosinophilic infiltrate (sensitivity 92%, specificity 68%), and absence of keratinocyte fraying (sensitivity 62%, specificity 58%). Features in the routinely processed biopsy were unable to reliably distinguish between epidermolysis bullosa acquisita and bullous pemphigoid. Direct immunofluorescence on salt-split skin remains the standard for differentiation.

  18. Molecular Characterization of Squamous Cell Carcinomas Derived from Recessive Dystrophic Epidermolysis Bullosa

    DTIC Science & Technology

    2005-06-01

    Carcinomas Derived from Recessive 5b. GRANT NUMBER Dystrophic Epidermolysis Bullosa DAMD17-02-1-0215 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...dystrophic epidermolysis bullosa (RDEB) frequently present with squamous cell carcinomas (SCCs) probably as a result of chronic blistering and extensive...12 Mahoney, M.G. INTRODUCTION Epidermolysis bullosa (EB) is a group of heritable

  19. Aspergillus flavus impairs antioxidative enzymes of Sternochetus mangiferae during mycosis.

    PubMed

    Jayanthi, Kamala P D; Ayyasamy, Arthikirubha; Kempraj, Vivek; Aurade, Ravindra M; Govindan, Selvakumar; Verghese, Abraham

    2015-01-01

    Insects depend upon cuticular, humoral and cellular defenses to resist mycosis. However, entomopathogenic fungi through co-evolution have developed mechanisms to counter such defenses. Although a plethora of mechanisms of mycosis by entomopathogenic fungi are well-established, studies on the impairment of insects' antioxidative enzymes during mycosis remain elusive. Here, we used the interaction of Sternochetus mangiferae and its associated entomopathogenic fungus, Aspergillus flavus, as a model to validate our hypothesis. Uninfected insects were exposed to fungal spores for infection to occur. We observed symptoms of mycosis within 48 h of incubation period. Biochemical studies on antioxidative enzymes namely catalase, peroxidase and phenoloxidase, in infected and uninfected insects revealed decreased activity of these enzymes. It appears that A. flavus disables the host's antioxidative enzyme system that plays a crucial role in elimination of oxidative toxins produced during mycosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Epidermolysis bullosa and congenital pyloric atresia

    PubMed Central

    Mithwani, Anwar Adil; Hashmi, Asif; Adil, Salman

    2013-01-01

    The association between epidermolysis bullosa (EB) and pyloric atresia (PA) is rare but well documented. Herein, we report a case of EB associated with congenital PA. A female baby, weighing 1480 g, was born vaginally to a 31-year-old gravida 7 lady at 33 weeks of gestation. Polyhydramnios was detected on antenatal assessment. The parents were non-consanguineous Saudis with no family history of significant illness. At birth, well-demarcated areas of peeled skin were present over knees, left leg and periumbilical region. Systemic examination revealed no other abnormality. On second day, the patient developed recurrent vomiting and abdominal distension. An abdominal X-ray revealed a single gastric gas bubble suggesting pyloric obstruction. Following gastroduodenostomy, the baby developed severe sepsis with multiorgan dysfunction and expired on 25th day of life. Skin biopsy showed cleavage within lamina lucida. PMID:24068383

  1. Diagnosis, treatment and management of epidermolysis bullosa.

    PubMed

    Watkins, Jean

    Epidermis bullosa is a genetically inherited disease in which painful blistering of the skin or mucous membranes occurs after minor trauma. It is a lifelong problem. The diagnosis should be confirmed by a specialist, preferably at a specialist unit where a treatment plan and follow-up arrangements for professionals and families can be put in place. Nurses will be involved in frequent dressings of wounds, after extra analgesia, and may need to be alert to any need for further specialist referral, especially in the case of complications such as infection, deformities, gastrointestinal strictures and possible skin cancers. Genetic counselling should also be offered to families, especially when considering the possible risks to future pregnancies.

  2. Laminin 332 in junctional epidermolysis bullosa

    PubMed Central

    Kiritsi, Dimitra; Has, Cristina; Bruckner-Tuderman, Leena

    2013-01-01

    Laminin 332 is an essential component of the dermal-epidermal junction, a highly specialized basement membrane zone that attaches the epidermis to the dermis and thereby provides skin integrity and resistance to external mechanical forces. Mutations in the LAMA3, LAMB3 and LAMC2 genes that encode the three constituent polypeptide chains, α3, β3 and γ2, abrogate or perturb the functions of laminin 332. The phenotypic consequences are diminished dermal-epidermal adhesion and, as clinical symptoms, skin fragility and mechanically induced blistering. The disorder is designated as junctional epidermolysis bullosa (JEB). This article delineates the signs and symptoms of the different forms of JEB, the mutational spectrum, genotype-phenotype correlations as well as perspectives for future molecular therapies. PMID:23076207

  3. Molecular therapies for inherited epidermolysis bullosa.

    PubMed

    Has, Cristina

    2016-08-01

    Inherited epidermolysis bullosa (EB) comprises rare genetic disorders characterized by formation of blisters and erosions of skin and mucous membranes after minor mechanical trauma. The molecular basis and the pathomechanisms of the main EB types have been largely deciphered in the past decades. The burden of the disease is high and quality of life strongly affected. The treatment is still symptomatic aiming to support wound healing and resolve complications. Numerous experimental therapeutic approaches for EB have been explored in the last years, most of them dedicated to dystrophic EB. Although gene and cell therapies have been already applied in patients, molecular therapies including gene editing and repurposing of small molecules are currently very attractive. Recent data on the effect of small molecules, like aminoglycosides and angiotensin receptor blockers in preclinical models for dystrophic EB are encouraging. The efficacy in patients remains to be proven in clinical trials. Therapeutic efficacy, as well as unexpected outcomes must be carefully monitored.

  4. CLINICAL MANAGEMENT FOR EPIDERMOLYSIS BULLOSA DYSTROPHICA

    PubMed Central

    Oliveira, Thais M.; Sakai, Vivien T.; Candido, Liliani A.; Silva, Salete M. B.; Machado, Maria Aparecida A. M.

    2008-01-01

    Epidermolysis bullosa (EB) consists of a group of genetic hereditary disorders in which patients frequently present fragile skin and mucosa that form blisters following minor trauma. More than 20 subtypes of EB have been recognized in the literature. Specific genetic mutations are well characterized for most the different EB subtypes and variants. The most common oral manifestations of EB are painful blisters affecting all the oral surfaces. Dental treatment for patients with EB consists of palliative therapy for its oral manifestations along with typical restorative and periodontal procedures. The aim of this article is to describe two dental clinical treatments of recessive dystrophic EB cases and their specific clinical manifestations. The psychological intervention required during the dental treatment of these patients is also presented. PMID:19089295

  5. Angina Bullosa Hemorrhagica: Report of 11 Cases

    PubMed Central

    Beguerie, Julieta Ruiz; Gonzalez, Silvina

    2014-01-01

    Angina bullosa hemorrhagica is a rare and benign disorder, usually localized in the subepithelial layer of the oral, pharyngeal and esophageal mucosa. The lesions are characterized by their sudden onset. They appear as a painless, tense, dark red and blood-filled blister in the mouth that rapidly expand and rupture spontaneously in 24-48 hours. The underlying etiopathology remains ill defined, although it may be a multifactorial phenomenon including diabetes, and steroid inhalers. The condition is not attributable to blood dyscrasias, nor other vesicular-bullous disorders. In this study, eleven patients with such blisters are described. Physical examination of the patients revealed a single blister with hemorrhagic content localized in the oral mucosa. Biopsy of the lesions showed sub epithelial blisters with a mild infiltrate. In general practice, dermatologists could face a blood-filled bullous lesion of the oral mucosa. Recognition is, therefore, of great importance for dermatologists. PMID:25386327

  6. Angina bullosa hemorrhagica: report of 11 cases.

    PubMed

    Beguerie, Julieta Ruiz; Gonzalez, Silvina

    2014-02-17

    Angina bullosa hemorrhagica is a rare and benign disorder, usually localized in the subepithelial layer of the oral, pharyngeal and esophageal mucosa. The lesions are characterized by their sudden onset. They appear as a painless, tense, dark red and blood-filled blister in the mouth that rapidly expand and rupture spontaneously in 24-48 hours. The underlying etiopathology remains ill defined, although it may be a multifactorial phenomenon including diabetes, and steroid inhalers. The condition is not attributable to blood dyscrasias, nor other vesicular-bullous disorders. In this study, eleven patients with such blisters are described. Physical examination of the patients revealed a single blister with hemorrhagic content localized in the oral mucosa. Biopsy of the lesions showed sub epithelial blisters with a mild infiltrate. In general practice, dermatologists could face a blood-filled bullous lesion of the oral mucosa. Recognition is, therefore, of great importance for dermatologists.

  7. Research Techniques Made Simple: Immunofluorescence Antigen Mapping in Epidermolysis Bullosa.

    PubMed

    Has, Cristina; He, Yinghong

    2016-07-01

    Inherited epidermolysis bullosa is a group of genetic blistering diseases with a broad spectrum of clinical severity and molecular defects. Epidermolysis bullosa results from mutations in genes encoding proteins involved in cell-cell and cell-matrix adhesion in the epidermis. Immunofluorescence antigen mapping makes use of monoclonal antibodies against proteins of the dermal-epidermal junction zone to determine the layer of skin where cleavage occurs and the relative protein abundance. It allows the diagnosis of the type and subtype of inherited epidermolysis bullosa and sheds light on molecular mechanisms underlying the disease. Immunofluorescence mapping steps include obtaining a skin biopsy sample, processing the biopsy material, antigen-antibody interaction on tissue, washing, incubation with fluorescently conjugated secondary antibodies, mounting, observation under a fluorescence microscope, and interpretation. A minimal antibody panel allows discrimination of the main epidermolysis bullosa subtypes. Extended panels can be used depending on the diagnostic or scientific question to be addressed. Immunofluorescence mapping contributed to significant progress in understanding epidermolysis bullosa, including identification of new underlying genetic mutations, mutation mechanisms, and the presence of revertant mosaicism. It is also an important tool in the assessment of the efficacy of experimental therapeutic approaches. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Oral Manifestations and Dental Management of Epidermolysis Bullosa Simplex

    PubMed Central

    Scheidt, Lisa; Sanabe, Mariane Emi

    2015-01-01

    ABSTRACT Epidermolysis bullosa (EB) is a group of hereditary chronic disorders, characterized by fragility of the skin and mucous membranes in response to minor mechanical trauma. The objective of this study was to report the case of a young girl diagnosed with epidermolysis bullosa simplex (EBS), transmitted by an autosomal dominant gene. Cutaneous findings included blisters and dystrophy following minimal friction. Recurrent blisters and vesicle formation on the hard palate were the main oral findings. In conclusion, publications concerning the oral and clinical manifestations of EBS are important for providing knowledge and an early multidisciplinary approach that prevents blister formation and improves these patients’ quality of life, with the dentist playing an important role in oral health management. How to cite this article: Scheidt L, Sanabe ME, Diniz MB. Oral Manifestations and Dental Management of Epidermolysis Bullosa Simplex. Int J Clin Pediatr Dent 2015;8(3):239-241. PMID:26604545

  9. Epidermolysis Bullosa Pruriginosa: Case Series and Review of the Literature.

    PubMed

    Kim, Whan B; Alavi, Afsaneh; Pope, Elena; Walsh, Scott

    2015-06-01

    Epidermolysis bullosa (EB) pruriginosa is a rare clinical subtype of dystrophic epidermolysis bullosa (DEB) that is characterized by intense pruritus resulting in hypertrophic, lichenified, prurigo-like plaques and nodules secondary to scratching. The variability in the age of onset, rarity of intact bullae, histologic ambiguities, and close resemblance to other conditions such as acquired inflammatory dermatoses may make diagnosis difficult for this unusual condition, for which fewer than 100 cases have been documented. In this report, we describe 3 cases of EB pruriginosa and review the current literature. © The Author(s) 2015.

  10. Epidermolysis bullosa simplex superficialis. A new variant of epidermolysis bullosa characterized by subcorneal skin cleavage mimicking peeling skin syndrome.

    PubMed

    Fine, J D; Johnson, L; Wright, T

    1989-05-01

    We report a new variant of epidermolysis bullosa simplex (EBS), termed EBS superficialis, which is characterized by the development of skin cleavage just beneath the level of stratum corneum. In two of seven patients identified, a second and more focal cleft within the lower third of the epidermis was also detected. Epidermolysis bullosa simplex superficialis appears to be transmitted as an autosomal dominant trait. It differs from other autosomal dominant forms of EBS by the common findings of milia and atrophic scarring, as well as involvement of oral and/or ocular surfaces. Epidermolysis bullosa simplex superficialis is further differentiated from peeling skin syndrome by the presence of blisters and the absence of spontaneous continual exfoliation or peeling.

  11. Recently Identified Forms of Epidermolysis Bullosa

    PubMed Central

    2015-01-01

    Epidermolysis bullosa (EB) comprises a collection of clinically diverse inherited blistering diseases that affect the skin and, in some subtypes, mucous membranes and other organs. Currently classified into four main subtypes (EB simplex, junctional EB, dystrophic EB, and Kindler syndrome, mainly based on the level of skin cleavage), the spectrum of EB extends to more than 30 clinical subtypes with pathogenic mutations in at least 18 distinct genes. This review focuses on three recent additions to variants of EB: all are autosomal recessive, and result from mutations in either DST-e (coding for epidermal dystonin, also known as the 230 kDa bullous pemphigoid antigen, BP230), EXPH5 (coding for exophilin-5, also known as Slac2-b), or ITGA3 (coding for the integrin alpha-3 subunit). Each of these new forms of EB is reviewed with respect to the initial gene discovery, clinical features, the current mutation database, and skin pathology. Awareness of these recently described forms of EB is helpful in the clinical evaluation of patients with EB and in defining genotype-phenotype correlation for inherited blistering skin diseases. PMID:26719633

  12. Dilated cardiomyopathy in dystrophic epidermolysis bullosa

    PubMed Central

    Sidwell, R; Yates, R; Atherton, D

    2000-01-01

    BACKGROUND—Dystrophic epidermolysis bullosa (DEB) is an uncommon genetic disorder of the skin and mucosae. In 1996, we reported the occurrence of lethal dilated cardiomyopathy (DCM) in two affected children.
METHODS—In the past seven years we have routinely screened patients with severe DEB who have been under the care of this hospital by yearly clinical review, echocardiography, and quantification of plasma selenium and carnitine concentrations, as deficiency of these micronutrients is known to be associated with the development of DCM.
RESULTS—Six of 61 children have developed DCM over the seven year period of this study, four of whom have not been previously reported, and three of whom have since died. We compared the concentrations of selenium and free and total carnitine in the children who developed DCM to concentrations in those with severe DEB who did not. The concentrations of free and total carnitine when first measured were significantly lower in the children with DCM, but the selenium concentrations were not.
CONCLUSIONS—We now believe that DCM is a not infrequent complication of severe recessive DEB, and may be related in part to carnitine concentrations, though the exact mechanism remains unclear. We therefore recommend that patients with this condition should undergo regular cardiac review including echocardiography.

 PMID:10869001

  13. [Aplasia cutis congenita associated with epidermolysis bullosa].

    PubMed

    Muñoz-Guerrero, Félix; Muñoz-Solís, Adrián Antonio; Ornelas-Aguirre, José Manuel

    2016-12-12

    Aplasia cutis congenita (ACC) is a skin condition of rare presentation, this disease is characterized by absence of skin at birth and associated with facial, skin and bone skull deformities. The diagnosis is mainly clinical. Male 5 days after birth, unique product of primigravida mother and no family history of relevance. Physical examination revealed bilateral and symmetrical skin defects of both lower extremities, the disease is characterized by skin fragility, scabs, and coated pseudomembrane ulcers, decreased interdigital space between toes of the left foot, retraction of the foot and genu varum. It was handled with allograft of epidermis cultured in vitro, general wound care and clinical follow-up. ACC associated with epidermolysis bullosa is one of the rarer forms of presentation. It is necessary to rule out other skin diseases. Clinical management is recommended with biological or synthetic skin cover, infection prevention, early treatment of complications and clinical follow. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  14. Silicon Phthalocyanine 4 and Photodynamic Therapy in Stage IA-IIA Cutaneous T-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-12-03

    Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome

  15. Age and etiology of childhood epidermolysis bullosa mortality.

    PubMed

    Hon, Kam Lun Ellis; Li, Joshua J; Cheng, Bernadette L; Luk, David C; Murrell, Dedee F; Choi, Paul C L; Leung, Alexander K C

    2015-04-01

    Epidermolysis bullosa (EB) is a heterogeneous group of congenital blistering diseases that are usually present in the neonatal period. They are characterized by blister formation in response to rubbing or frictional trauma. EB is classified into three major categories, each with many subtypes based on the precise location at which separation or blistering occurs, namely epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB), and dystrophic epidermolysis bullosa (DEB). We describe the causes and ages of death of three cases of EB in Hong Kong. A 24-year-old male with EBD diagnosed in the neonatal period lived a withdrawn life after completing secondary school and died of metastaic squamous cell carcinoma. Two neonates of consanguineous Pakistani parents, one with JEB and the other with EB-Pyloric Atresia variant, died of sepsis in infancy. We performed an extensive literature review of the causes and ages of death of these diseases. EB is a heterogeneous inherited blistering skin disease associated with significant morbidity and mortality. EBS is occasionally associated with death at early ages with sepsis. Patients with JEB usually died of sepsis at young age. DEB patients often survive to adulthood and die of cardiopulmonary and renal complications. Squamous cell carcinoma and metastases are unique in DEB.

  16. Children with Rare Chronic Skin Diseases: Hemangiomas and Epidermolysis Bullosa.

    ERIC Educational Resources Information Center

    Jones, Sheila Dove; Miller, Cynthia Dieterich

    The paper reports on studies involving children having the rare chronic skin diseases of hemangiomas and epidermolysis bullosa (characterized by easy blistering). One study compared the self-concept and psychosocial development of young (mean age 46 months) children (N=19) with hemangiomas with 19 children without hemangiomas. Findings indicated…

  17. Angina bullosa hemorrhagica: an unusual problem following periodontal therapy.

    PubMed

    Curran, A E; Rives, R W

    2000-11-01

    Angina bullosa hemorrhagica (ABH) describes benign subepithelial oral blood blisters not attributable to a systemic disorder. Little is known about the pathogenesis of ABH, although most cases have been associated with mild trauma prior to appearance of the lesion. This report discusses the clinical and histopathologic features of ABH which appeared after routine scaling and root planing.

  18. Specific affinity between fibronectin and the epidermolysis bullosa acquisita antigen.

    PubMed Central

    Woodley, D T; O'Keefe, E J; McDonald, J A; Reese, M J; Briggaman, R A; Gammon, W R

    1987-01-01

    Autoantibodies in the skin and sera of patients with epidermolysis bullosa acquisita bind to a large matrix molecule within the lamina densa region of skin basement membrane. At the site of these immune complexes, the epidermis separates from the dermis, which creates a subepidermal blister just below the lamina densa. The target molecule for the autoantibodies is in close apposition to fibronectin, a major extracellular matrix molecule that is abundant in the upper dermis of skin. In this report, we show specific affinity between fibronectin and the 290,000-D chain of the epidermolysis bullosa acquisita antigen, and that this affinity is mediated by the gelatin/collagen-binding domain of fibronectin (Mr = 60,000). Since blistering in epidermolysis bullosa acquisita often occurs in the absence of clinical and histological inflammation, a direct interruption in the fibronectin-epidermolysis bullosa acquisita antigen bond may be involved in the pathogenesis of epidermal-dermal disadherence that occurs in this bullous disease. Images PMID:3584471

  19. Children with Rare Chronic Skin Diseases: Hemangiomas and Epidermolysis Bullosa.

    ERIC Educational Resources Information Center

    Jones, Sheila Dove; Miller, Cynthia Dieterich

    The paper reports on studies involving children having the rare chronic skin diseases of hemangiomas and epidermolysis bullosa (characterized by easy blistering). One study compared the self-concept and psychosocial development of young (mean age 46 months) children (N=19) with hemangiomas with 19 children without hemangiomas. Findings indicated…

  20. Epidermolysis bullosa care in Austria and the Epidermolysis Bullosa House Austria.

    PubMed

    Pohla-Gubo, Gabriela; Hintner, Helmut

    2010-04-01

    The Epidermolysis Bullosa (EB) House Austria is a special unit for the multidisciplinary management of children and adults with EB. Major advances in EB care have been made possible by a multidisciplinary approach including most of the medical specialties offered at the General Hospital in Salzburg. The EB House Austria is independently funded by the support group DEBRA Austria. As the EB House Austria fulfills all criteria for a European Union reference center, as stated by the Rare Disease Task Force in 2005, the authors hope that in the near future the EB House Austria will be accepted as such on a European Union level and that they can soon get financial support from this side. This support would be of even more importance in the moment when a causative cure, which is of course supposed to be a cost-intensive gene therapy, is available.

  1. Molecular Characterization of Squamous Cell Carcinomas From Recessive Dystrophic Epidermolysis Bullosa

    DTIC Science & Technology

    2006-09-01

    AD Award Number: DAMD17-02-1-0215 TITLE: Molecular Characterization of Squamous Cell Carcinomas from Recessive Dystrophic Epidermolysis Bullosa ...Squamous Cell Carcinomas from Recessive 5b. GRANT NUMBER Dystrophic Epidermolysis Bullosa DAMD17-02-1-0215 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Patients with recessive dystrophic epidermolysis bullosa (RDEB) frequently present with squamous

  2. Guttural pouch mycosis in six horses in New Zealand.

    PubMed

    Archer, R M; Knight, C G; Bishop, W J

    2012-05-01

    Six horses from several geographical locations in New Zealand presented with signs of guttural pouch mycosis. All horses had experienced epistaxis within 14 days of presentation. In five horses with epistaxis, a diagnosis of guttural pouch mycosis was made on endoscopic observation of fungal plaques in the affected guttural pouches. One of these cases died before surgery was attempted. The remaining four cases underwent ligation and balloon catheter occlusion of the internal carotid artery of the affected pouch. Three of these horses survived and were reported to be healthy 1 year after surgery. One case died from haemorrhage 8 weeks after surgery. In a sixth horse, endoscopy was carried out but the affected guttural pouch which had recently haemorrhaged was not entered. This horse underwent ligation of the internal carotid and occipital arteries of the affected side but subsequently died. A diagnosis of guttural pouch mycosis of the maxillary artery was confirmed by post-mortem examination. Histology revealed fungal hyphae within thrombi in the lumen of the maxillary artery in the affected guttural pouch. Two horses displayed signs consistent with cranial nerve damage in the guttural pouch. Guttural pouch mycosis. This is the first report of which we are aware of the diagnosis and treatment of clinical cases of guttural pouch mycosis in horses in New Zealand. Practitioners in New Zealand should be aware of the presence and manifestations of this disease and be prepared to treat or refer horses for surgical treatment before fatal haemorrhage and/or profound neurologic signs occur.

  3. 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

  4. Advances in understanding and treating dystrophic epidermolysis bullosa

    PubMed Central

    Vanden Oever, Michael J

    2014-01-01

    Epidermolysis bullosa is a group of inherited disorders that can be both systemic and life-threatening. Standard treatments for the most severe forms of this disorder, typically limited to palliative care, are ineffective in reducing the morbidity and mortality due to complications of the disease. Emerging therapies—such as the use of allogeneic cellular therapy, gene therapy, and protein therapy—have all shown promise, but it is likely that several approaches will need to be combined to realize a cure. For recessive dystrophic epidermolysis bullosa, each particular therapeutic approach has added to our understanding of type VII collagen (C7) function and the basic biology surrounding the disease. The efficacy of these therapies and the mechanisms by which they function also give us insight into developing future strategies for treating this and other extracellular matrix disorders. PMID:24860657

  5. Bone Marrow Transplantation for Recessive Dystrophic Epidermolysis Bullosa

    PubMed Central

    Wagner, John E.; Ishida-Yamamoto, Akemi; McGrath, John A.; Hordinsky, Maria; Keene, Douglas R.; Riddle, Megan J.; Osborn, Mark J.; Lund, Troy; Dolan, Michelle; Blazar, Bruce R.; Tolar, Jakub

    2010-01-01

    Background Recessive dystrophic epidermolysis bullosa is an incurable, often fatal mucocutaneous blistering disease caused by mutations in COL7A1, the gene encoding type VII collagen (C7). On the basis of preclinical data showing biochemical correction and prolonged survival in col7−/− mice, we hypothesized that allogeneic marrow contains stem cells capable of ameliorating the manifestations of recessive dystrophic epidermolysis bullosa in humans. Methods Between October 2007 and August 2009, we treated seven children who had recessive dystrophic epidermolysis bullosa with immunomyeloablative chemotherapy and allogeneic stem-cell transplantation. We assessed C7 expression by means of immunofluorescence staining and used transmission electron microscopy to visualize anchoring fibrils. We measured chimerism by means of competitive polymerase-chain-reaction assay, and documented blister formation and wound healing with the use of digital photography. Results One patient died of cardiomyopathy before transplantation. Of the remaining six patients, one had severe regimen-related cutaneous toxicity, with all having improved wound healing and a reduction in blister formation between 30 and 130 days after transplantation. We observed increased C7 deposition at the dermal–epidermal junction in five of the six recipients, albeit without normalization of anchoring fibrils. Five recipients were alive 130 to 799 days after transplantation; one died at 183 days as a consequence of graft rejection and infection. The six recipients had substantial proportions of donor cells in the skin, and none had detectable anti-C7 antibodies. Conclusions Increased C7 deposition and a sustained presence of donor cells were found in the skin of children with recessive dystrophic epidermolysis bullosa after allogeneic bone marrow transplantation. Further studies are needed to assess the long-term risks and benefits of such therapy in patients with this disorder. (Funded by the National

  6. Tinea corporis bullosa due to Trichophyton schoenleinii: case report.

    PubMed

    Mareş, Mihai; Năstasă, Valentin; Apetrei, Ingrid Cezara; Suditu, Gabriela Cristina

    2012-10-01

    We report the first case of tinea corporis bullosa due to Trichophyton schoenleinii in a 41-year-old Romanian woman, without any involvement of the scalp and hair. The species identification was performed using macroscopic and microscopic features of the dermatophyte and its physiological abilities. Epidemiological aspects of the case are also discussed. The general treatment with terbinafine and topical applications of ciclopiroxolamine cream have led to complete healing, with the lesions disappearing in 2 weeks.

  7. [Hereditary epidermolysis bullosa in Tunisia: an epidemio-clinical and ultrastructural study].

    PubMed

    Cherif, F; Mnajja, N; Feriani, S; Ben Saïd, Z Marrakchi; Jaafoura, M H; Dhahri, A Ben Osman; Boubaker, S

    2005-01-01

    Hereditary epidermolysis bullosa (EB) are a group of genodermatoses whose common primary feature is formation of blisters following minor trauma. The aim of the present study was to assess epidemiological, clinical, genetical and histological particularities of patients with hereditary epidermolysis bullosa.

  8. [Congenital epidermolysis bullosa--a case report].

    PubMed

    Konefał, Halina; Gawrych, Elzbieta; Czeszyńska, Maria Beata

    2012-10-01

    Bullous dermatitis in infants is a clinical term used for a number of disorders associated with primary neonatal pemphigus. The disease requires differentiation of autoimmune disorders such as pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid. These diseases are the result of pemphigus IgG antibodies that pass from the mother to the fetus through the placenta. The level of antibody titers in the pregnant woman and her clinical condition are not the markers of the severity of the disease in children, but, in case of a high level, a miscarriage premature birth, or even stillbirth, may occur. Staphylococcal syndrome exfoliative dermatitis (staphylococcal scalded skin syndrome - SSSS), the etiological agents of which are type A or B exfoliative toxins of Staphylococcus aureus, is most frequently observed. These toxins can activate as superantigens and cause T-cell activation. They induce proteolysis and separation of the granular layer of epidermis through direct binding of these antigens. Symptoms of the disorder regardless of the etiologic factors, are common: redness of the skin and formation of bubbles of various sizes filed with serous or serous-bloody content. Bursting bubbles patches peel off, leaving bare, sometimes oozing surface. Extensive damage to the skin is a gateway to infection and disturbs the function of regulating warmth and water-electrolyte balance. Early detection of the cause and appropriate general and local treatment effectively prevent the development of sepsis. The authors present a case of a full-term neonate (male, birthweight 3230 g, good overall condition, 5-min Apgar score: 10) born with dermatitis bullosa of unknown etiology Physical examination immediately after birth revealed multiple blisters filled with serous and serous-bloody content on the skin all over the neonatal body mostly in the area of both armpits, elbows, wrists, knees, ankles and fingers of both hands and feet. The course of pregnancy was uncomplicated

  9. [Dementia in Patients with Central Nervous System Mycosis].

    PubMed

    Morita, Akihiko; Ishihara, Masaki; Konno, Michiko

    2016-04-01

    Central nervous system (CNS) mycosis is a potentially life-threatening but treatable neurological emergency. CNS mycoses progress slowly and are sometimes difficult to distinguish from dementia. Though most patients with CNS mycosis have an underlying disease, such as human immunodeficiency virus (HIV) infection, cancer, diabetes mellitus, and/or use of immunosuppressants, cryptococcosis can occur in non-immunosuppressed persons. One of the major difficulties in accurate diagnosis is to detect the pathogen in patients' cerebrospinal fluid (CSF) cultures. Thus, the clinical diagnosis is often made by combining circumstantial evidence, including mononuclear cell-dominant pleocytosis with low glucose and protein elevation in the CSF, as well as positive results from an antigen-based assay and a (1-3)-beta-D-glucan assay using plasma and/or CSF. Polymerase chain reaction (PCR)-based diagnostics, which are not performed as routine examinations and are mostly performed as part of academic research in Japan, are sensitive tools for the early diagnosis of CNS mycosis. Mognetic resonance imaging (MRI) is useful to assess the complications of fungal meningitis, such as abscess, infarction, and hydrocephalus. Clinicians should realize the advantages and disadvantages of these diagnostic tools. Early and accurate diagnosis, including identification of the particular fungal species, enables optimal antifungal treatment that produces good outcomes in patients with CNS mycosis.

  10. Clinical analysis of 68 patients with pulmonary mycosis in China

    PubMed Central

    2011-01-01

    Background Due to the lack of specific clinical manifestations and imaging features, the diagnosis of pulmonary mycosis is difficult. This study aimed to investigate the pathogens, clinical manifestations, imaging features, diagnosis and management of pulmonary mycosis. Methods Data on 68 patients diagnosed as pulmonary mycosis in Xiang Ya hospital from January 2001 to December 2010 were collected and their clinical manifestations, radiographic characterization, diagnostic methods and management were analyzed. Results All patients were diagnosed by pathological examination. Of the 68 cases, 38 (55.9%) had pulmonary aspergillosis and 19 (27.9%) pulmonary cryptococcosis. Open-lung surgery was performed in 38 patients (55.9%), transbronchial biopsy in 15 (22.0%), and computerized tomography (CT) guided percutaneous needle biopsy in 11 (16.2%). Main symptoms were as follows: cough in 51 cases (75.0%), expectoration in 38 (55.9%), hemoptysis in 25 (37.8%), fever in 20 (29.4%), while 6 cases (11.1%) were asymptomatic. X-ray and chest CT showed masses or nodular lesions in 52 cases (76.5%), patchy lesions in 10 (14.7%), cavity formation in 15 (22.0%), and diffuse miliary nodules in 1 case. In 51 cases (75.0%) misdiagnosis before pathological examination occurred. Surgical resection was performed in 38 patients (55.9%). In 25 patients (36.7%) systemic antifungal therapy was administered, and 20 patients (29.4%) experienced complete responses or partial responses. Conclusion The main pathogens of pulmonary mycosis are Aspergillus, followed by cryptococcosis. Final diagnosis of pulmonary mycosis mainly depends on pathological examination. The clinical manifestations, imaging features, diagnostic methods and management differ depending on the pathogens. Satisfactory therapy can be obtained by both antifungal and surgical treatment. PMID:22958675

  11. Exophiala pisciphila: a novel cause of allergic bronchopulmonary mycosis

    PubMed Central

    Mador, M. Jeffery

    2016-01-01

    Allergic bronchopulmonary mycosis (ABPM) is a hypersensitivity reaction to fungal antigens, which may particularly plague uncontrolled asthmatics. Non-aspergillus fungal organisms may be implicated and may elicit a more severe immunologic response. Exophiala pisciphila, a marine organism, has not been reported as a culprit yet. However, this report indicates it may be implicated in unrelenting symptoms in a severe asthmatic patient who had become dependent on corticosteroids. Proper identification and adequate therapy of this organism led to complete resolution of respiratory symptoms, with adequate subsequent control of the asthma. ABPM may complicate asthma and lead to a lack of its control. Proper awareness, testing and treatment of non-aspergillus pulmonary mycosis is essential to proper asthma care and beneficial for its control. PMID:27499992

  12. Clinical features and diagnosis of epidermolysis bullosa acquisita.

    PubMed

    Vorobyev, Artem; Ludwig, Ralf J; Schmidt, Enno

    2017-02-01

    Epidermolysis bullosa acquisita (EBA) is a rare autoimmune blistering disease of skin and mucous membranes. EBA is caused by autoantibodies against type VII collagen, which is a major component of anchoring fibrils, attaching epidermis to dermis. Binding of autoantibodies to type VII collagen leads to skin fragility and, finally, blister formation. The clinical picture of EBA is polymorphic, with several distinct phenotypes being described. Despite recent progress in understanding the pathophysiology of EBA, its diagnosis is still challenging. Areas covered: This review provides an update on the clinical manifestations and diagnostic methods of EBA. We searched PubMed using the terms 'epidermolysis bullosa acquisita' covering articles in English between 1 January 2005 and 31 May 2016. Relevant older publications were retrieved form cited literature. Expert commentary: While the clinical picture is highly variable, diagnosis relies on direct immunofluorescence (IF) microscopy of a perilesional skin biopsy. Linear deposits of IgG, IgA and/or C3 along the dermal-epidermal junction with an u-serrated pattern are diagnostic for EBA alike the detection of serum autoantibodies against type VII collagen. Several test systems for the serological diagnosis of EBA have recently become widely available. In some patients, sophisticated diagnostic approaches only available in specialized centers are required.

  13. Management of digestive lesions associated to congenital epidermolysis bullosa.

    PubMed

    Chahed, Jamila; Mekki, Mongi; Ksia, Amine; Kechiche, Nehla; Hidouri, Saida; Youssef, Trimech Monia; Sahnoun, Lassaad; Krichene, Imed; Belghith, Mohsen; Nouri, Abdellatif

    2015-01-01

    Congenital epidermolysis bullosa (CEB) is a rare genodermatosis. The digestive system is very frequently associated with skin manifestations. Pyloric atresia (PA) and oesophageal stenosis (OS) are considered the most serious digestive lesions to occur.The aim of this work is to study the management and the outcome of digestive lesions associated to CEB in four children and to compare our results to the literature. A retrospective study of four observations: Two cases of PA and two cases of OS associated to CEB managed in the Paediatric Surgery Department of Fattouma Bourguiba Teaching Hospital in Monastir, Tunisia. Four patients, two of them are 11 and 8 years old, diagnosed as having a dystrophic epidermolysis bullosa since the neonatal period. They were admitted for the investigation of progressive dysphagia. Oesophageal stenosis was confirmed by an upper contrast study. Pneumatic dilation was the advocated therapeutic method for both patients with a favourable outcome. The two other patients are newborns, diagnosed to have a CEB because of association of PA with bullous skin lesions with erosive scars. Both patients had a complete diaphragm excision with pyloroplasty. They died at the age of 4 and 3 months of severe diarrhoea resistant to medical treatment. Digestive lesions associated to CEB represent an aggravating factor of a serious disease. OS complicating CEB is severe with difficult management. Pneumatic dilatation is the gold standard treatment method. However, the mortality rate in PA with CEB is high. Prenatal diagnosis of PA is possible, and it can help avoiding lethal forms.

  14. Epidermolysis bullosa. Part 1: causes, presentation and complications.

    PubMed

    Pillay, Elizabeth

    This article is the first in a series of three focusing on the causes, clinical presentation, complications and care of adult patients affected by epidermolysis bullosa (EB), a group of rare genetic skin fragility disorders. Although the condition is rare, in some cases it presents extreme challenges both to those affected and those involved in the care of the EB patient; therefore, these articles may have relevance for other long-term disorders. While there is a wealth of information regarding the 'science' of EB there is dearth of information regarding the care of the adult EB patient, and this series of articles will endeavour to fill that gap. This article focuses mainly on those patients affected with the most severe form of EB found in the adult group, recessive dystrophic epidermolysis bullosa; with the part two looking at the care of the adult with EB from the nursing perspective, including wound management, and the experiences of a specialist EB psychotherapist being presented in the final article of the series. Readers will thus have an opportunity to gain an overall view of this difficult condition.

  15. Epidermolysis bullosa pruriginosa: a case with a novel mutation and co-existent lichen amyloidosus.

    PubMed

    Chen, Qiping; Lee, Joyce Siong-See; Tey, Hong Liang

    2015-01-01

    Epidermolysis bullosa pruriginosa is a rare variant of dystrophic epidermolysis bullosa characterized by severely pruritic and cicatricial lesions localized to the extensor extremities. We report a Singaporean Chinese male with epidermolysis bullosa pruriginosa with an underlying novel mutation in the COL7A1 gene. A heterozygous acceptor splice site mutation IVS67-1G>T probably led to in-frame skipping of exon 68 (36-basepairs), resulting in a loss of 12 amino acids. Among his three children, only the youngest son, who had bilateral big toenail thickening, possessed the same mutation. His skin biopsy one decade ago revealed association of focal amyloidosis; a recent skin biopsy showed more established features of lichen amyloidosis. It is debatable whether the cutaneous amyloidosis was a secondary or primary phenomenon. Our report highlights that the diagnosis of epidermolysis bullosa pruriginosa may be obscured when cutaneous amyloidosis is coexistent.

  16. Epidermolysis bullosa acquisita in a 17-year-old boy with Crohn's disease.

    PubMed

    Russo, Irene; Ferrazzi, Anna; Zanetti, Irene; Alaibac, Mauro

    2015-07-10

    Epidermolysis bullosa acquisita is a rare, acquired, autoimmune subepidermal blistering disease of the skin, characterised by blisters and erosions, especially in trauma-prone sites and extensor skin surface, scarring with formation of milia, skin fragility and nail dystrophy. Epidermolysis bullosa acquisita is extremely rare in childhood and it has been reported to be frequently associated with Crohn's disease. Furthermore, autoantibodies against type VII collagen have been found in a large number of patients with Crohn's disease without epidermolysis bullosa acquisita. We report a case of a 17-year-old boy affected by Crohn's disease who presented with milia on infiltrated erythematous plaques over the back of the hands. The diagnosis of epidermolysis bullosa acquisita was confirmed by histopathology, direct and indirect immunofluorescence analysis and ELISA. 2015 BMJ Publishing Group Ltd.

  17. Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize Functional Mechanisms of Sulfur Mustard Injury to Human Skin

    DTIC Science & Technology

    2005-03-01

    AD Award Number: DAMD17-01-1-0688 TITLE: Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize Functional Mechanisms of Sulfur...2005 Final 1 May 2001 -28 Feb 2005 4. TITLE AND SUBTITLE 5a, CONTRACT NUMBER Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize... Epidermolysis Bullosa (JEB) patients (#552), that lack a functional y2 chain of laminin 5 and do not adhere to BM, were transduced with retroviral vectors (TASK

  18. Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize Functional Mechanisms of Sulfur Mustard Injury to Human Skin

    DTIC Science & Technology

    2004-05-01

    AD Award Number: DAMD17-01-1-0688 TITLE: Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize Functional Mechanisms of Sulfur...30 Apr 2004) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Novel Tissue Models of Junctional Epidermolysis Bullosa DAMD17-01-1-0688 to Characterize...further explore the role of BM in decreased SM susceptibility, primary keratinocytes harvested from Junctional Epidermolysis Bullosa (JEB) patients (#552

  19. Epidermolysis bullosa pruriginosa showing good response to low-dose thalidomide - a report of two cases.

    PubMed

    Ranugha, P S S; Mohanan, S; Chandrashekar, L; Basu, D; Thappa, D M; Rajesh, N G

    2014-01-01

    Epidermolysis bullosa pruriginosa is a rare distinctive variant of dystrophic epidermolysis bullosa characterized by intense pruritus, lichenified plaques in linear distribution, and anonychia. It is a difficult condition to treat and causes a great deal of distress. The present authors report two cases showing good response to low-dose thalidomide, with clinical and symptomatic improvement. The exact mechanism of action is not yet clear. © 2013 Wiley Periodicals, Inc.

  20. Reduced Toxicity Conditioning and Allogeneic Hematopoietic Progenitor Cell Transplantation for Recessive Dystrophic Epidermolysis Bullosa.

    PubMed

    Geyer, Mark B; Radhakrishnan, Kavita; Giller, Roger; Umegaki, Noriko; Harel, Sivan; Kiuru, Maija; Morel, Kimberly D; LeBoeuf, Nicole; Kandel, Jessica; Bruckner, Anna; Fabricatore, Sandra; Chen, Mei; Woodley, David; McGrath, John; Baxter-Lowe, LeeAnn; Uitto, Jouni; Christiano, Angela M; Cairo, Mitchell S

    2015-09-01

    Recessive dystrophic epidermolysis bullosa is a severe, incurable, inherited blistering disease caused by COL7A1 mutations. Emerging evidence suggests hematopoietic progenitor cells (HPCs) can be reprogrammed into skin; HPC-derived cells can restore COL7 expression in COL7-deficient mice. We report two children with recessive dystrophic epidermolysis bullosa treated with reduced-toxicity conditioning and HLA-matched HPC transplantation.

  1. Structural variations in anchoring fibrils in dystrophic epidermolysis bullosa: correlation with type VII collagen expression.

    PubMed

    McGrath, J A; Ishida-Yamamoto, A; O'Grady, A; Leigh, I M; Eady, R A

    1993-04-01

    Dystrophic epidermolysis bullosa is characterized by various abnormalities of anchoring fibrils, which are mainly composed of type VII collagen, at the dermal-epidermal junction. To define these changes more clearly, we examined skin samples from 22 patients with different forms of dystrophic epidermolysis bullosa by pre-embedding immunoelectron microscopy using an antibody (LH 7:2) that binds to the NC-1 globular domain of type VII collagen, followed by 1 nm colloidal gold-labeled secondary antibodies and subsequent silver enhancement. In dominant dystrophic epidermolysis bullosa cases, there was only a slight but variable reduction in the immunolabeling density on anchoring fibrils and on the lamina densa, in parts similar to normal human skin. In localized recessive dystrophic epidermolysis bullosa skin, some fibrillar structures just below the lamina densa (and particularly subjacent to hemidesmosomes) had specific antibody labeling despite their lack of resemblance to definitive anchoring fibrils. Immunolabeling with LH 7:2 was also seen within basal keratinocyte endoplasmic reticulum and cytoplasmic vesicles in some dystrophic epidermolysis bullosa patients, usually with milder phenotypic features. Even in the most severe cases of generalized recessive dystrophic epidermolysis bullosa, occasional immunolabeling was found within the lamina densa and on scanty thin filamentous structures at sub-lamina densa sites usually occupied by anchoring fibrils. This study suggests that dystrophic epidermolysis bullosa patients express some type VII collagen NC-1 domain epitopes that may be variably reduced at the dermal-epidermal junction or retained within basal keratinocytes. The clinical heterogeneity in dystrophic epidermolysis bullosa is mirrored by a range of immunoelectron microscopy findings, indicating variability in completeness of anchoring fibril formation and a possible spectrum of underlying type VII collagen structural protein abnormalities.

  2. Liver Transplant in a Patient With Acquired Epidermolysis Bullosa and Associated End-Stage Liver Disease.

    PubMed

    Vennarecci, Giovanni; Miglioresi, Lucia; Guglielmo, Nicola; Pelle, Fabio; Santoro, Roberto; Andreuccetti, Jacopo; Ceribelli, Cecilia; Stella, Pietro; Angelo, Corrado; Ettorre, Giuseppe Maria

    2017-06-01

    We report the first case of a liver transplant in a patient with epidermolysis bullosa acquisita and associated hepatitis B virus-hepatitis D virus cirrhosis and its inherent technical issues. Epidermolysis bullosa acquisita is an autoimmune multisystem disorder involving skin and mucosa characterized by the appearing of blisters and erosions. The more severe forms may result in nutritional compromise, anemia, osteopenia, dilated cardiomyopathy, laryngeal mucosal involvement, esophageal strictures, bladder, and kidney involvement requiring surgical intervention. Epidermolysis bullosa acquisita has become recognized as a multisystem disorder that poses several surgical challenges. This case shows that liver transplant is a feasible procedure in patients affected by epidermolysis bullosa acquisita. Patients with epidermolysis bullosa acquisita require a particular pretransplant assessment and a dedicated intra- and postoperative management of every invasive procedure that can traumatize the skin and mucosal epithelium to achieve an uneventful liver transplant. Epidermolysis bullosa acquisita does not represent a contraindication to liver transplant, and immunosuppression after transplant may favor a good systemic control of this immunologic disorder.

  3. Concha bullosa, nasal septal deviation and paranasal sinusitis; a computed tomographic evaluation.

    PubMed

    Javadrashid, R; Naderpour, M; Asghari, S; Fouladi, D F; Ghojazadeh, M

    2014-01-01

    Although concha bullosa, nasal septal deviation (NSD) and paranasal sinusitis are apparently three independent entities, some studies suggest that they are interconnected. Computed tomography (CT) is a useful and accurate imaging modality for examining this interconnection. The objective of this study is to use CT imaging to investigate the possible association between concha bullosa, NSD and paranasal sinusitis. We reviewed 206 nasal and paranasal CT images of individuals with sinonasal symptoms/cosmetic issues and investigated the association between the presence of concha bullosa and NSD with paranasal sinusitis. There was no significant relation between the presence of concha bullosa and paranasal sinusitis. The mean NSD was significantly higher in the cases with frontal, maxillary, ethmoid and sphenoid sinusitis than in unaffected subjects. Similar findings were found in the patients with any involved paranasal sinus and the controls (6.49 +/- 3.060 vs. 3.31 +/- 1.99 degrees; p<0.001). An NSD > or =3.5% differentiated between the presence and absence of paranasal sinusitis, with a sensitivity and specificity of 77.8% and 76.5%, respectively. A significant positive correlation was found between NSD and the number of involved sinuses (Pearson's r=0.58, p<0.001). The laterality of sinusitis was not associated with NSD or concha bullosa. Nasal septal deviation, but possibly not concha bullosa, is associated with paranasal sinusitis and its extent. An NSD > or = 3.5 degrees is a useful predictor of paranasal sinusitis.

  4. Junctional epidermolysis bullosa incidence and survival: 5-year experience of the Dystrophic Epidermolysis Bullosa Research Association of America (DebRA) nurse educator, 2007 to 2011.

    PubMed

    Kelly-Mancuso, Geraldine; Kopelan, Brett; Azizkhan, Richard G; Lucky, Anne W

    2014-01-01

    Junctional epidermolysis bullosa (JEB) is a particularly devastating type of epidermolysis bullosa, especially in the newborn period. Data about the number of new cases of JEB in the United States were collected from the records of the Dystrophic Epidermolysis Bullosa Research Association of America (DebRA) nurse educator. Seventy-one children with JEB were reported to have been born in the 5 years between 2007 and 2011, reflecting an incidence of at least 3.59 per million per year, significantly higher than previously estimated (2.04 per million). There was a high prevalence of morbidity and infant mortality of at least 73%, as 52 of the 71 cases proved fatal by June 2012. These data emphasize the need for future research to develop treatment and ultimately a cure for this disorder.

  5. Placenta-based therapies for the treatment of epidermolysis bullosa

    PubMed Central

    Nevala-Plagemann, Christopher; Lee, Catherine; Tolar, Jakub

    2015-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering skin disease caused by mutations in the COL7A1 gene. These mutations lead to decreased or absent levels of collagen VII at the dermal-epidermal junction. Over the past decade, significant progress has been made in the treatment of RDEB, including the use of hematopoietic cell transplantation, but a cure has proven elusive. Patients still experience life-limiting and life-threatening complications as a result of painful and debilitating wounds. The continued suffering of these patients drives the need to improve existing therapies and develop new ones. In this review, we will discuss how recent advances in placenta-, umbilical cord blood- and amniotic membrane-based therapies may play a role in the both the current and future treatment of RDEB. PMID:25795271

  6. Immune mechanism-targeted treatment of experimental epidermolysis bullosa acquisita.

    PubMed

    Ludwig, Ralf

    2015-01-01

    Epidermolysis bullosa acquisita (EBA) is an autoimmune bullous dermatosis characterized by chronic mucocutaneous blistering caused by autoantibodies directed against type VII collagen. EBA causes a high morbidity and is difficult to treat. Model systems have significantly broadened our understanding of EBA pathogenesis, leading to the identification of numerous therapeutic targets. Of these, so far, a few have been evaluated for their therapeutic potential in preclinical models. In mice, EBA can be induced by transfer of anti-type VII collagen antibodies or by immunization with the protein. The latter model, immunization-induced EBA, is ideal to test drugs for their therapeutic efficacy. Here, mice with already established disease can be treated for prolonged periods. Albeit time consuming, results from immunization-induced EBA will pave the way for clinical application in patients. As the key pathogenic principle, that is, autoantibody-induced, leukocyte-mediated tissue injury and inflammation, is shared by other diseases, these findings may have translational applications beyond EBA.

  7. Use of fibre dressings in children with severe epidermolysis bullosa.

    PubMed

    Denyer, Jacqueline; Gibson, Elaine

    This non-comparative study explored the benefits of a natural gelling fibre dressing in 10 children with epidermolysis bullosa (EB). The clinical challenge in managing these children is that they often present with recalcitrant wounds that are perpetuated by critical colonisation, presence of biofilms and infection. KytoCel® (Aspen Medical) is a highly absorbent dressing composed of natural, biodegradable acylated chitosan. These fibres bond with wound exudate to form a clear gel that locks in fluid absorbs pathogens and is conformable to the wound bed. It also has haemostatic properties. ( Dutta PK et al, 2004 ; Lee et al, 2009 ; Stephen Haynes et al, 2014 ). Factors considered were whether the dressing could aid healing, reduce bleeding, reduce bioburden, be atraumatic and comfortable during wear time and removal.

  8. Epidermolysis bullosa simplex: a paradigm for disorders of tissue fragility

    PubMed Central

    Coulombe, Pierre A.; Kerns, Michelle L.; Fuchs, Elaine

    2009-01-01

    Epidermolysis bullosa (EB) simplex is a rare genetic condition typified by superficial bullous lesions that result from frictional trauma to the skin. Most cases are due to dominantly acting mutations in either keratin 14 (K14) or K5, the type I and II intermediate filament (IF) proteins tasked with forming a pancytoplasmic network of 10-nm filaments in basal keratinocytes of the epidermis and in other stratified epithelia. Defects in K5/K14 filament network architecture cause basal keratinocytes to become fragile and account for their trauma-induced rupture. Here we review how laboratory investigations centered on keratin biology have deepened our understanding of the etiology and pathophysiology of EB simplex and revealed novel avenues for its therapy. PMID:19587453

  9. Necrotizing mycosis due to Verruconis gallopava in an immunocompetent patient.

    PubMed

    Geltner, Christian; Sorschag, Sieglinde; Willinger, Birgit; Jaritz, Thomas; Saric, Zoran; Lass-Flörl, Cornelia

    2015-12-01

    Verruconis gallopava is a dematiaceous mould usually causing saprophytic infection in immunosuppressed host. Only a few cases have been published even in immunocompromised states. We present a rare case of pulmonary involvement in an immunocompetent patient with recurrent disease. The mid-aged woman had no evidence of any disease causing impaired immune response. Recurrent disease shows pulmonary infiltrates and symptoms of allergic bronchopulmonary mycosis. We describe an emerging pathogen that has been found in an immunocompetent host. Eradication was not possible despite the use of several different antifungal drugs. Further recurrence of infection in the described patient is probable.

  10. A rare case of human mycosis by Rhizoctonia solani.

    PubMed

    Kaore, N M; Atul, A R; Khan, M Z; Ramnani, V K

    2012-01-01

    Rhizoctonia solani is a most widely recognized strong saprophyte with a great diversity of host plants. It is a first ever case of extensive human mycosis caused by Rhizoctonia solani in a 65-year-old diabetic and hypertensive farmer, with a history of head injury caused by fall of mud wall. Necrotic material collected revealed septate fungal hyphae with bacterial co-infection. Fungal culture on SDA at 25°C showed cotton wooly growth progressing to greyish-white to shiny metallic black colonies and identified on basis of septate mycelial growth without conidia, right angle branching, presence of compact hyphal forms and anastomosis between branching hyphae on LPCB mount.

  11. Computed tomographic spectrum of intracranial mycosis: correlation with histopathology

    SciTech Connect

    Whelan, M.A.; Stern, J.; deNapoli, R.A.

    1981-12-01

    Four cases of intracerebral fungal infection are reviewed. The clinical course is outlined, and the computed tomographic (CT) characteristics are analyzed in light of known pathological data. The CT appearance of intracranial mycosis is dependent on the type of fungus as well as the dominant infecting form, i.e., yeast or hyphae. The hyphal form leads predominantly to a CT pattern consistent with vascular occlusion and secondary abscess formation; the yeast form generally results in noncaseating granulomas, which appear on CT scan as nodular enhancing lesions. If the patient survives the acute infective process, these fungal lesions undergo a prolonged subacute phase, and may eventually calcify.

  12. Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa.

    PubMed

    Esposito, Susanna; Guez, Sophie; Orenti, Annalisa; Tadini, Gianluca; Scuvera, Giulietta; Corti, Laura; Scala, Alessia; Biganzoli, Elia; Berti, Emilio; Principi, Nicola

    2016-09-24

    In order to evaluate the serum anti-skin autoantibodies and cytokine concentrations in patients with different epidermolysis bullosa (EB) types and severity, 42 EB patients and 38 controls were enrolled. Serum anti-skin antibodies were significantly higher in the patients than in the controls (p = 0.008, p < 0.001, p < 0.001, p < 0.001 and p < 0.001 for desmoglein 1 (DSG1) desmoglein 3 (DSG3), bullous pemphigoid 180 (BP180), BP230 and type VII collagen (COL7), respectively). The same trend was observed for interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor-β, and interferon-γ (p < 0.001, p < 0.001, p < 0.001, p = 0.008, p < 0.001 and p = 0.002, respectively). Increases in anti-skin antibodies and cytokine concentrations were higher in patients with recessive dystrophic EB than in those with different types of EB, in generalized cases than in localized ones, and in patients with higher Birmingham Epidermolysis Bullosa Severity (BEBS) scores than in those with a lower score. The BEBS score was directly correlated with BP180, BP230, COL7 (p = 0.015, p = 0.008 and p < 0.001, respectively) and IL-6 (p = 0.03), whereas IL-6 appeared significantly associated with DSG1, DSG3, BP180, BP230 and COL7 (p = 0.015, p = 0.023, p = 0.023, p = 0.015 and p = 0.005, respectively). This study showed that autoimmunity and inflammatory responses are frequently activated in EB, mainly in severe forms, suggesting the use of immunosuppressive drugs or biologicals that are active against pro-inflammatory cytokines to reduce clinical signs and symptoms of disease.

  13. The risk of cardiomyopathy in inherited epidermolysis bullosa

    PubMed Central

    Fine, J-D; Hall, M; Weiner, M; Li, K-P; Suchindran, C

    2008-01-01

    Background Case reports have suggested that cardiomyopathy may be a complication of recessive dystrophic epidermolysis bullosa (RDEB). Objective To determine the risk of congestive heart failure (CHF) or cardiomyopathy in each major EB subtype. Methods These data represent systematic case findings and data collection performed throughout the continental United States from 1986 through 2002, by the National Epidermolysis Bullosa Registry. Study design is cross-sectional (n = 3280) with a nested randomly sampled longitudinal subcohort (n = 450). Frequencies of CHF and cardiomyopathy were determined by patient self-reporting, medical histories and review of medical records. In those who died, death certificates were reviewed and histories obtained from surviving family. Cumulative risks were stratified by cause and EB subtype. Results Cardiomyopathy was reported as early as within the first year of life. In patients having no other known risk factors for CHF or cardiomyopathy, the highest risk of cardiomyopathy was seen among patients with Hallopeau–Siemens RDEB (RDEB-HS), with a cumulative risk of 4·51% on or after age 20 years. The cumulative risk of cardiomyopathy was only 1·14% and 0·40% in non-Herlitz junctional EB (JEB) and non-Hallopeau–Siemens RDEB, respectively, and was not observed in any other EB subtype. When patients with coexistent chronic renal failure were included, the cumulative risk for RDEB-HS rose to 18·86% by age 35 years. About 30% of our patients affected with RDEB-HS died of CHF or cardiomyopathy, even those with no other known risk factors. Conclusions CHF and cardiomyopathy are uncommon complications in both major RDEB subtypes and non-Herlitz JEB, and may be fatal. PMID:18616785

  14. Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa

    PubMed Central

    Esposito, Susanna; Guez, Sophie; Orenti, Annalisa; Tadini, Gianluca; Scuvera, Giulietta; Corti, Laura; Scala, Alessia; Biganzoli, Elia; Berti, Emilio; Principi, Nicola

    2016-01-01

    In order to evaluate the serum anti-skin autoantibodies and cytokine concentrations in patients with different epidermolysis bullosa (EB) types and severity, 42 EB patients and 38 controls were enrolled. Serum anti-skin antibodies were significantly higher in the patients than in the controls (p = 0.008, p < 0.001, p < 0.001, p < 0.001 and p < 0.001 for desmoglein 1 (DSG1) desmoglein 3 (DSG3), bullous pemphigoid 180 (BP180), BP230 and type VII collagen (COL7), respectively). The same trend was observed for interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor-β, and interferon-γ (p < 0.001, p < 0.001, p < 0.001, p = 0.008, p < 0.001 and p = 0.002, respectively). Increases in anti-skin antibodies and cytokine concentrations were higher in patients with recessive dystrophic EB than in those with different types of EB, in generalized cases than in localized ones, and in patients with higher Birmingham Epidermolysis Bullosa Severity (BEBS) scores than in those with a lower score. The BEBS score was directly correlated with BP180, BP230, COL7 (p = 0.015, p = 0.008 and p < 0.001, respectively) and IL-6 (p = 0.03), whereas IL-6 appeared significantly associated with DSG1, DSG3, BP180, BP230 and COL7 (p = 0.015, p = 0.023, p = 0.023, p = 0.015 and p = 0.005, respectively). This study showed that autoimmunity and inflammatory responses are frequently activated in EB, mainly in severe forms, suggesting the use of immunosuppressive drugs or biologicals that are active against pro-inflammatory cytokines to reduce clinical signs and symptoms of disease. PMID:27669234

  15. Management of digestive lesions associated to congenital epidermolysis bullosa

    PubMed Central

    Chahed, Jamila; Mekki, Mongi; Ksia, Amine; Kechiche, Nehla; Hidouri, Saida; Youssef, Trimech Monia; Sahnoun, Lassaad; Krichene, Imed; Belghith, Mohsen; Nouri, Abdellatif

    2015-01-01

    Background: Congenital epidermolysis bullosa (CEB) is a rare genodermatosis. The digestive system is very frequently associated with skin manifestations. Pyloric atresia (PA) and oesophageal stenosis (OS) are considered the most serious digestive lesions to occur. The aim of this work is to study the management and the outcome of digestive lesions associated to CEB in four children and to compare our results to the literature. Patients and Methods: A retrospective study of four observations: Two cases of PA and two cases of OS associated to CEB managed in the Paediatric Surgery Department of Fattouma Bourguiba Teaching Hospital in Monastir, Tunisia. Results: Four patients, two of them are 11 and 8 years old, diagnosed as having a dystrophic epidermolysis bullosa since the neonatal period. They were admitted for the investigation of progressive dysphagia. Oesophageal stenosis was confirmed by an upper contrast study. Pneumatic dilation was the advocated therapeutic method for both patients with afavourable outcome. The two other patients are newborns, diagnosed to have a CEB because of association of PA with bullous skin lesions with erosive scars. Both patients had a complete diaphragm excision with pyloroplasty. They died at the age of 4 and 3 months of severe diarrhoea resistant to medical treatment. Conclusion: Digestive lesions associated to CEB represent an aggravating factor of a serious disease. OS complicating CEB is severe with difficult management. Pneumatic dilatation is the gold standard treatment method. However, the mortality rate in PA with CEB is high. Prenatal diagnosis of PA is possible, and it can help avoiding lethal forms. PMID:26712284

  16. Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma

    ClinicalTrials.gov

    2017-01-03

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome

  17. Epidermolysis bullosa and the partnership with autoimmunity: what should we assimilate?

    PubMed

    Esposito, Susanna; Guez, Sophie; Manzoni, Francesca; Bosco, Annalisa; Rigante, Donato

    2015-02-01

    Bullous skin diseases are characterized by genetic abnormalities related to structural epidermal proteins or organ-specific autoantibodies against the same proteins and are revealed by blister formation on skin or mucous membranes, with differences in blister depth, morphology, and topography. Both inherited and autoimmune forms of these disorders can be framed in the context of epidermolysis bullosa. Their clinical spectrum varies from early lethal to mild variants with normal life expectancy, and several distinct phenotypes differ for age of onset, extent, location and depth of skin and mucous lesions, or scarring severity. Recently, different inflammatory processes blended with autoimmune phenomena have been demonstrated in both inherited and acquired epidermolysis bullosa, revealing that this overlapping might cause substantial implications in terms of disease course and outcome. Although several associations between epidermolysis bullosa in its different variants and autoimmune diseases have been reported, it is not yet completely clear how it happens and why this association occurs in only some patients. Autoantibodies are the primary cause of the disease in acquired epidermolysis bullosa, whereas they can be produced as a secondary event due to genetically determined skin damage in inherited epidermolysis bullosa, contributing significantly to the worsening of the disease. The awareness of this overlap may help in identifying new therapeutic approaches with immunosuppressive drugs that could have a significant impact in terms of prognosis.

  18. The use of Biochip immunofluorescence microscopy for the serological diagnosis of epidermolysis bullosa acquisita.

    PubMed

    Marzano, Angelo Valerio; Cozzani, Emanuele; Biasin, Matteo; Russo, Irene; Alaibac, Mauro

    2016-05-01

    Epidermolysis bullosa acquisita is a rare autoimmune bullous disease characterized by the presence of circulating antibodies directed against the collagen type VII. Diagnosis is generally based on clinical history, clinical features, histology, direct and indirect immunofluorescence, immunoblotting and ELISA. Our study aims to determine the validity of the Biochip immunofluorescence microscopy for the serological diagnosis of epidermolysis bullosa acquisita. Six patients with epidermolysis bullosa acquisita and presence of antibodies against type VII collagen confirmed by ELISA were included in the study. Subsequently, all sera of patients were analyzed using Biochip. Antibodies anti-collagen type VII were detected in all sera by means of the Biochip technology. Thus, Biochip shows a good correlation with ELISA and seems to be an appropriate method for the diagnosis of epidermolysis bullosa acquisita. It is an easy, fast and standardized method which could facilitate the diagnosis of this autoimmune bullous disease. We suggest that it could be used as an initial screening test to identify patients with epidermolysis bullosa acquisita.

  19. Pseudostertagia bullosa (Nematoda: Trichostrongyloidea) in artiodactyl hosts from North America: redescription and comments on systematics.

    PubMed

    Hoberg, E P; Abrams, A

    2005-04-01

    A relationship for Pseudostertagia bullosa within the trichostrongyloids has been enigmatic or unresolved. Studies of the synlophe in males and females of P. bullosa revealed a tapering system anterior to the deirids and a pattern of parallel ridges extending to near the caudal extremity in both lateral and median fields. Structurally, the synlophe differs considerably from that seen among the Cooperiinae and exhibits homoplasy with respect to ridge systems among some Ostertagiinae. Other structural characters due to symplesiomorphy, homoplasy or because they represent autapomorphies do not serve to reveal the putative relationships for P. bullosa with other trichostrongyloids. Although somewhat equivocal, the 2-2-1 pattern of the bursa and position of rays 2 and 3 suggest an association with the Cooperinae, as postulated by Durette-Desset and others. Pseudostertagia bullosa appears to be a species that has survived in the pronghorn, Antilocapra americana, a relictual pecoran artiodactyl that occurs in xeric regions of western North America; pronghorn are the sole remnant of the late Tertiary radiation for Antilocapridae across North America. Pseudostertagia bullosa may occur in mixed infections with a number of ostertagiines in the abomasa of mule deer (Odocoileus hemionus) and domestic sheep (Ovis aries) in regions of sympatry for pronghorn and these artiodactyl hosts.

  20. Nutritional aspects of children and adolescents with epidermolysis bullosa: literature review*

    PubMed Central

    Zidorio, Ana Paula Caio; Dutra, Eliane Said; Leão, Dryelle Oliveira Dias; Costa, Izelda Maria Carvalho

    2015-01-01

    Epidermolysis Bullosa is a genetic disorder that affects mainly the skin, however, all others systems are influenced. The nutritional care of children and adolescents with Epidermolysis Bullosa is a key treatment strategy, since the energy needs are increased due to the disease's metabolism, burdening the immune system and cicatrization process, symptoms caused by the disease hinder the intake and adequate absorption of nutrients, which may result in inadequate growth and development. Because this is a rare disease, there are few professionals who know the characteristics of both the clinical evolution and nutritional and dietary treatments. This literature review discusses the latest knowledge on energy and specific nutrient requirements to the dietary treatment and monitoring of children and adolescents with Epidermolysis Bullosa. PMID:25830992

  1. Nutritional aspects of children and adolescents with epidermolysis bullosa: literature review.

    PubMed

    Zidorio, Ana Paula Caio; Dutra, Eliane Said; Leão, Dryelle Oliveira Dias; Costa, Izelda Maria Carvalho

    2015-01-01

    Epidermolysis Bullosa is a genetic disorder that affects mainly the skin, however, all others systems are influenced. The nutritional care of children and adolescents with Epidermolysis Bullosa is a key treatment strategy, since the energy needs are increased due to the disease's metabolism, burdening the immune system and cicatrization process, symptoms caused by the disease hinder the intake and adequate absorption of nutrients, which may result in inadequate growth and development. Because this is a rare disease, there are few professionals who know the characteristics of both the clinical evolution and nutritional and dietary treatments. This literature review discusses the latest knowledge on energy and specific nutrient requirements to the dietary treatment and monitoring of children and adolescents with Epidermolysis Bullosa.

  2. Homocysteine metabolism in children and adolescents with epidermolysis bullosa.

    PubMed

    De Giuseppe, Rachele; Venturelli, Greta; Guez, Sophie; Salera, Simona; De Vita, Claudia; Consonni, Dario; Dellanoce, Cinzia; Bamonti, Fabrizia; Chiarelli, Gabriella; Manzoni, Francesca; Maiavacca, Rita; Esposito, Susanna

    2016-10-29

    Epidermolysis bullosa (EB) belongs to a family of rare heterogeneous, genetic disorders characterized by blistering of the skin and mucous membranes in response to minor mechanical trauma. The involvement of the oral mucosa and oesophagus stenosis is suggested to be responsible for severe nutritional deficiencies, but few studies have till now considered this aspect. This observational study aimed to evaluate homocysteine status in children and adolescents with EB by assessing total plasma homocysteine (tHcy) and metabolically related vitamins (B6, B12, folate) concentrations. Twenty EB patients (12 M; age range 0.5-19 years) were evaluated for: plasma tHcy, serum B12 and holotranscobalamin (HoloTC, the active fraction of B12), serum and erythrocyte folate (s-F and Ery-F, respectively), plasma B6 and serum high sensitive C-reactive-protein (hsCRP) levels. Clinical severity was also evaluated through the Birmingham Epidermolysis Bullosa Severity (BEBS) score. A sex and age well-matched population was also enrolled. EB patients showed tHcy levels higher (p = 0.04) and B6 levels lower (p = 0.03) than controls. B12, HoloTC, s-F and ery-F concentrations did not differ between patients and controls. Multiple linear regression analysis showed that tHcy levels were independent of the metabolically related vitamins levels. In addition, serum hsCRP levels were higher in EB patients than in controls (p = 0.003) and correlated negatively with B6 concentrations (r = -0.6; p = 0.009). BEBS score correlated negatively with HoloTC (p = 0.022) and B6 (p = 0.005) levels and positively with age (p = 0.031) and hsCRP levels (p < 0.001). The assessment of tHcy and metabolically related vitamin levels describes an important aspect of EB patients' nutritional status which can result essential for their long term care. Monitoring B6 levels in EB patients could be particularly important in order to prevent several complications associated with B6

  3. [Anesthesia for cesarean section in a patient with recessive dystrophic epidermolysis bullosa].

    PubMed

    García, I; Manrique, S; Muñoz, C; López-Gil, M V; Munar, F; Montferrer, N

    2009-11-01

    Recessive dystrophic epidermolysis bullosa is inherited as a rare autosomal disorder which causes blisters to form in the skin. We describe the treatment of a 39-year-old parturient with this condition. She was scheduled for elective cesarean section at 37 weeks' gestation. The patient had widespread skin lesions, had lost fingers, and had esophageal stenosis. The cesarean was performed under spinal anesthesia without complications. Recessive dystrophic epidermolysis bullosa requires adaptation of anesthetic technique that includes control over posture and careful handling of the skin. Material for attaching monitoring devices and inserting venous lines must be adapted to the particular deformities and skin lesions present.

  4. Dental and Anaesthetic Challenges in a Patient with Dystrophic Epidermolysis Bullosa

    PubMed Central

    Al-Abadi, Ali; Al-Azri, Salah A.; Bakathir, Abdulaziz; Al-Riyami, Yusra

    2016-01-01

    Epidermolysis bullosa is a group of rare genetic disorders characterised by skin and mucous membrane fragility and systemic manifestations of variable severity. We report a case of dystrophic epidermolysis bullosa in an 18-year-old male patient who presented to the Department of Oral Health at Sultan Qaboos University Hospital, Muscat, Oman, in 2015 with recurrent dental pain and infections. Due to the poor dental status of the patient and anticipated operative difficulties due to microstomia and limited mouth opening, the patient underwent full dental clearance under general anaesthesia. This article discusses the dental and anaesthetic challenges encountered during the management of this patient and provides a brief literature review. PMID:28003899

  5. Scanning electron microscopy of a blister roof in dystrophic epidermolysis bullosa.

    PubMed

    Almeida, Hiram Larangeira de; Monteiro, Luciane; Marques e Silva, Ricardo; Rocha, Nara Moreira; Scheffer, Hans

    2013-01-01

    In dystrophic epidermolysis bullosa the genetic defect of anchoring fibrils leads to cleavage beneath the basement membrane, with its consequent loss. We performed scanning electron microscopy of an inverted blister roof of a case of dystrophic epidermolysis bullosa, confirmed by immunomapping and gene sequencing. With a magnification of 2000 times a net attached to the blister roof could be easily identified. This net was composed of intertwined flat fibers. With higher magnifications, different fiber sizes could be observed, some thin fibers measuring around 80 nm and thicker ones measuring between 200 and 300 nm.

  6. Scanning electron microscopy of a blister roof in dystrophic epidermolysis bullosa*

    PubMed Central

    de Almeida Jr., Hiram Larangeira; Monteiro, Luciane; Silva, Ricardo Marques e; Rocha, Nara Moreira; Scheffer, Hans

    2013-01-01

    In dystrophic epidermolysis bullosa the genetic defect of anchoring fibrils leads to cleavage beneath the basement membrane, with its consequent loss. We performed scanning electron microscopy of an inverted blister roof of a case of dystrophic epidermolysis bullosa, confirmed by immunomapping and gene sequencing. With a magnification of 2000 times a net attached to the blister roof could be easily identified. This net was composed of intertwined flat fibers. With higher magnifications, different fiber sizes could be observed, some thin fibers measuring around 80 nm and thicker ones measuring between 200 and 300 nm. PMID:24474107

  7. Reduced anchoring fibril formation and collagen VII immunoreactivity in feline dystrophic epidermolysis bullosa.

    PubMed

    Olivry, T; Dunston, S M; Marinkovich, M P

    1999-11-01

    Dystrophic epidermolysis bullosa was diagnosed in a cat with juvenile-onset epithelial sloughing of the oral mucosa, footpads, and haired skin. Dermoepidermal separation occurred in the absence of inflammation or cytolysis of basal epidermal cells. Collagen IV-specific immunostaining corroborated the fact that clefting took place below the epidermal basement membrane. Ultrastructural examination revealed that the proband's anchoring fibrils exhibited a filamentous morphology and were decreased in number compared with those in a normal cat. Finally, the attenuated immunoreactivity for collagen VII in our patient led us to suspect that its encoding gene, COL7A1, could be mutated in this case of feline dystrophic epidermolysis bullosa.

  8. Allergic bronchopulmonary mycosis due to Alternaria: Case report and review.

    PubMed

    Singh, Bhagteshwar; Denning, David W

    2012-01-01

    While allergic bronchopulmonary aspergillosis and mycosis are well recognised, no cases have been described related to Alternaria spp. Alternaria is a common sensitising fungus in asthmatics and related to thunderstorm asthma. We report a case of an asthmatic who presented with worsening asthma control, mild eosinophilia on high dose inhaled corticosteroids (800 μg/day), a total IgE of 3800 KIU/L, an Alternaria-specific IgE of 21.3 KUa/L and positive skin prick test, negative specific IgE and skin prick test to Aspergillus fumigatus, Penicillium spp., Cladosporium spp., Trichophyton spp. and a normal CT scan of the thorax. He responded well to a short course of oral prednisolone and then oral itraconazole, given over 17 months but relapsed 1 month after stopping it.

  9. Allergic bronchopulmonary mycosis due to Alternaria: Case report and review

    PubMed Central

    Singh, Bhagteshwar; Denning, David W.

    2012-01-01

    While allergic bronchopulmonary aspergillosis and mycosis are well recognised, no cases have been described related to Alternaria spp. Alternaria is a common sensitising fungus in asthmatics and related to thunderstorm asthma. We report a case of an asthmatic who presented with worsening asthma control, mild eosinophilia on high dose inhaled corticosteroids (800 μg/day), a total IgE of 3800 KIU/L, an Alternaria-specific IgE of 21.3 KUa/L and positive skin prick test, negative specific IgE and skin prick test to Aspergillus fumigatus, Penicillium spp., Cladosporium spp., Trichophyton spp. and a normal CT scan of the thorax. He responded well to a short course of oral prednisolone and then oral itraconazole, given over 17 months but relapsed 1 month after stopping it. PMID:24371728

  10. Epidemiology of Inherited Epidermolysis Bullosa Based on Incidence and Prevalence Estimates From the National Epidermolysis Bullosa Registry.

    PubMed

    Fine, Jo-David

    2016-11-01

    Accurate estimation of the incidence and prevalence of each subtype of epidermolysis bullosa (EB) is essential before clinical trials can be designed and sufficient funding allocated by government agencies and third-party insurers for the care of these individuals. To determine the incidence and prevalence of inherited EB stratified by subtype in the United States during a 16-year period. Prospective cross-sectional and longitudinal study. Data were obtained from 3271 patients consecutively enrolled in the National Epidermolysis Bullosa Registry from January 1, 1986, through December 31, 2002, using a detailed instrument created with the assistance of the National Institutes of Health. Analyses were performed in January 1999 and April 2015. Participants were patients of all ages with EB. Extensive clinical and laboratory data were collected on patients who were subclassified and serially revalidated based on published diagnostic recommendations by an international panel of experts. Pertinent to this report, estimates were made of the incidence and prevalence during 2 time frames. During the first 5 years of funding of the registry, the overall incidence and prevalence of inherited EB were 19.60 and 8.22 per 1 million live births, respectively. When reassessed over the entire 16 years of the study, the prevalence rose to 11.07, whereas the overall incidence remained unchanged at 19.57 cases. Changes were also observed within some disease subsets as increased numbers of patients were identified, recruited, followed up longitudinally, and resubclassified as needed over time. For example, in 2002, the prevalence of EBS overall and localized EBS had increased considerably by 30.4% and 25.5%, respectively, whereas the prevalence of generalized intermediate EBS declined by 76.7% as a result of later subclassification of some of those patients into other subtypes. In contrast, no significant change was noted in the overall prevalence of JEB or generalized severe JEB

  11. Ichthyosis bullosa of Siemens: response to topical tazarotene.

    PubMed

    Rajiv, S; Rakhesh, S V

    2006-01-01

    In 1937, Siemens described a Dutch family with superficial blistering, flexural hyperkeratosis, and characteristic mauserung appearance. Since then, less than 20 kindreds with this condition have been described in the English dermatologic literature. A 14-year-old boy presented with history of recurrent blistering and peeling of skin since the age of 1 month, predominantly seen over limbs and trunk, often associated with secondary infection. His mother also had similar symptoms from childhood. On examination, the child had typical mauserung peeling of the skin and dirty gray hyperkeratosis in a rippled pattern over flexures. Skin biopsy from the boy showed intracorneal blistering with epidermolytic hyperkeratosis in the upper spinous layers. The typical history and clinical features along with characteristic histological findings confirmed our diagnosis of ichthyosis bullosa of Siemens. It must be differentiated from other conditions with epidermolytic hyperkeratosis and skin peeling, such as bullous ichthyosiform erythroderma of Brocq and peeling skin syndrome. Our patient responded well to 0.05% topical tazarotene gel over four weeks.

  12. Clinical Presentation, Pathogenesis, Diagnosis, and Treatment of Epidermolysis Bullosa Acquisita

    PubMed Central

    Ludwig, Ralf J.

    2013-01-01

    Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin blistering disease. The pathogenic relevance of autoantibodies targeting type VII collagen (COL7) has been well-documented. Therefore, EBA is a prototypical autoimmune disease with a well-characterized pathogenic relevance of autoantibody binding to the target antigen. EBA is a rare disease with an incidence of 0.2 new cases per million and per year. The current treatment of EBA relies on general immunosuppressive therapy, which does not lead to remission in all cases. Therefore, there is a high, so far unmet medical need for the development of novel therapeutic options. During the last 10 years, several novel in vitro and in vivo models of EBA have been established. These models demonstrated a critical role of the genetic background, T cells, and cytokines for mediating the loss of tolerance towards COL7. Neutrophils, complement activation, Fc gamma receptor engagement, cytokines, several molecules involved in cell signaling, release of reactive oxygen species, and matrix metalloproteinases are crucial for autoantibody-induced tissue injury in EBA. Based on this growing understanding of the diseases' pathogenesis, several potential novel therapeutic targets have emerged. In this review, the clinical presentation, pathogenesis, diagnosis, and current treatment options for EBA are discussed in detail. PMID:23956869

  13. Treatment of hereditary epidermolysis bullosa: updates and future prospects.

    PubMed

    Hsu, Chao-Kai; Wang, Sheng-Pei; Lee, Julia Yu-Yun; McGrath, John A

    2014-02-01

    Epidermolysis bullosa (EB) represents a group of inherited blistering skin diseases, some forms of which are associated with considerable morbidity and increased mortality. Notably, in recessive dystrophic EB there can be extensive muco-cutaneous fragility and disease complications such as scars, contractures, anemia, malnutrition, and malignancy. Currently, there is no effective therapy or cure for EB. Over the last decade, however, a number of important advances have been made that are bringing new treatments closer to the clinic, including gene therapy, protein replacement therapy, cell therapies [allogeneic fibroblasts, mesenchymal stromal cells (MSCs), bone marrow stem cell transplantation, culturing/grafting revertant mosaic keratinocytes], gene editing/engineering, and clinical application of inducible pluripotent stem cells. Although a cure for EB still remains elusive, recent data on animal models and initial human clinical trials have raised the expectations of patients, clinicians, and researchers that disease modification and improved quality of life are feasible goals. Furthermore, the lessons learned in treating EB are likely to have significant implications for improving the management of other genetic diseases.

  14. Prevalence and Characterization of Pruritus in Epidermolysis Bullosa

    PubMed Central

    Danial, Christina; Adeduntan, Rasidat; Gorell, Emily S.; Lucky, Anne W.; Paller, Amy S.; Bruckner, Anna; Pope, Elena; Morel, Kimberly D.; Levy, Moise L.; Li, Shufeng; Gilmore, Elaine S.; Lane, Alfred T

    2014-01-01

    Background Qualitative data suggest that pruritus is a burdensome symptom in patients with epidermolysis bullosa (EB), but the prevalence of pruritus in children and adults with EB, as well as factors that contribute to pruritus are unknown. Objective To quantitatively identify and to characterize pruritus experienced by EB patients using a comprehensive online questionnaire. Methods A questionnaire was developed to evaluate pruritus in all ages and types of EB. Questions that characterize pruritus were included, and factors that aggravate symptoms were investigated. Patients from seven North American EB centers were invited to participate. Results A total of 146 out of 216 questionnaires were completed (response rate=68%) (73 males, 73 females; median age, 20.0). Using a 5-point Likert scale (1=never, 2=rarely, 3=sometimes, 4=often, 5=always), itchiness was the most bothersome EB complication (mean=3.3). The average daily frequency of pruritus increased with self-reported EB severity. Pruritus was most frequent at bedtime (mean=3.8) and interfered with sleep. Factors that aggravated pruritus included healing wounds, dry skin, infected wounds, stress, heat, dryness, and humidity. Conclusions Pruritus is common in EB patients and can be very bothersome. Future studies will need to investigate the most effective treatments given to EB patients for pruritus. PMID:25236506

  15. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification.

    PubMed

    Fine, Jo-David; Bruckner-Tuderman, Leena; Eady, Robin A J; Bauer, Eugene A; Bauer, Johann W; Has, Cristina; Heagerty, Adrian; Hintner, Helmut; Hovnanian, Alain; Jonkman, Marcel F; Leigh, Irene; Marinkovich, M Peter; Martinez, Anna E; McGrath, John A; Mellerio, Jemima E; Moss, Celia; Murrell, Dedee F; Shimizu, Hiroshi; Uitto, Jouni; Woodley, David; Zambruno, Giovanna

    2014-06-01

    Several new targeted genes and clinical subtypes have been identified since publication in 2008 of the report of the last international consensus meeting on diagnosis and classification of epidermolysis bullosa (EB). As a correlate, new clinical manifestations have been seen in several subtypes previously described. We sought to arrive at an updated consensus on the classification of EB subtypes, based on newer data, both clinical and molecular. In this latest consensus report, we introduce a new approach to classification ("onion skinning") that takes into account sequentially the major EB type present (based on identification of the level of skin cleavage), phenotypic characteristics (distribution and severity of disease activity; specific extracutaneous features; other), mode of inheritance, targeted protein and its relative expression in skin, gene involved and type(s) of mutation present, and--when possible--specific mutation(s) and their location(s). This classification scheme critically takes into account all published data through June 2013. Further modifications are likely in the future, as more is learned about this group of diseases. The proposed classification scheme should be of value both to clinicians and researchers, emphasizing both clinical and molecular features of each EB subtype, and has sufficient flexibility incorporated in its structure to permit further modifications in the future. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  16. A consensus approach to wound care in epidermolysis bullosa

    PubMed Central

    Pope, Elena; Lara-Corrales, Irene; Mellerio, Jemima; Martinez, Anna; Schultz, Gregory; Burrell, Robert; Goodman, Laurie; Coutts, Patricia; Wagner, John; Allen, Upton; Sibbald, Gary

    2013-01-01

    Background Wound care is the cornerstone of treatment for patients with epidermolysis bullosa (EB); however, there are currently no guidelines to help practitioners care for these patients. Objectives The objective of this study was to generate a list of recommendations that will enable practitioners to better care for patients with EB. Methods An expert panel generated a list of recommendations based on the best evidence available. The recommendations were translated into a survey, and sent to other EB experts to generate consensus using an online-based modified Delphi method. The list was refined and grouped into themes and specific recommendations. Results There were15 respondents (45% response rate), with significant experience in the EB field (>10 years [67%]). Respondents included physicians (67%), nurses (17%), and allied health professionals (7%). There was more than 85% agreement for all the proposed items. These were further refined and grouped into 5 main themes (assessment and management of factors that impair healing, patient-centered concerns, local wound care, development of an individualized care plan, and organizational support) and 17 specific recommendations. Limitations There is a paucity of scientific evidence with most recommendations based on expert opinion. Conclusions These recommendations will provide practitioners with a framework for caring for these patients. Additional scientific research including effectiveness studies for everyday practice and expert consensus, may further refine these recommendations. PMID:22387035

  17. Inherited epidermolysis bullosa: new diagnostic criteria and classification.

    PubMed

    Intong, Lizbeth R A; Murrell, Dédée F

    2012-01-01

    Epidermolysis bullosa (EB) is a group of inherited, mechanobullous disorders caused by mutations in various structural proteins in the skin. There have been several advances in the classification of EB since it was first introduced in the late 19th century. We now recognize four major types of EB, depending on the location of the target proteins and level of the blisters: EB simplex (epidermolytic), junctional EB (lucidolytic), dystrophic EB (dermolytic), and Kindler syndrome (mixed levels of blistering). This contribution will summarize the most recent classification and discuss the molecular basis, target genes, and proteins involved. We have also included new subtypes, such as autosomal dominant junctional EB and autosomal recessive EB due to mutations in the dystonin (DST) gene, which encodes the epithelial isoform of bullouspemphigoid antigen 1. The main laboratory diagnostic techniques-immunofluorescence mapping, transmission electron microscopy, and mutation analysis-will also be discussed. Finally, the clinical characteristics of the different major EB types and subtypes will be reviewed. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms

    PubMed Central

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-01-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)—a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  19. A consensus approach to wound care in epidermolysis bullosa.

    PubMed

    Pope, Elena; Lara-Corrales, Irene; Mellerio, Jemima; Martinez, Anna; Schultz, Gregory; Burrell, Robert; Goodman, Laurie; Coutts, Patricia; Wagner, John; Allen, Upton; Sibbald, Gary

    2012-11-01

    Wound care is the cornerstone of treatment for patients with epidermolysis bullosa (EB); however, there are currently no guidelines to help practitioners care for these patients. The objective of this study was to generate a list of recommendations that will enable practitioners to better care for patients with EB. An expert panel generated a list of recommendations based on the best evidence available. The recommendations were translated into a survey, and sent to other EB experts to generate consensus using an online-based modified Delphi method. The list was refined and grouped into themes and specific recommendations. There were 15 respondents (45% response rate), with significant experience in the EB field (>10 years [67%]). Respondents included physicians (67%), nurses (17%), and allied health professionals (7%). There was more than 85% agreement for all the proposed items. These were further refined and grouped into 5 main themes (assessment and management of factors that impair healing, patient-centered concerns, local wound care, development of an individualized care plan, and organizational support) and 17 specific recommendations. There is a paucity of scientific evidence with most recommendations based on expert opinion. These recommendations will provide practitioners with a framework for caring for these patients. Additional scientific research including effectiveness studies for everyday practice and expert consensus, may further refine these recommendations. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  20. Epidermolysis bullosa in calves in the United Kingdom.

    PubMed

    Foster, A P; Skuse, A M; Higgins, R J; Barrett, D C; Philbey, A W; Thomson, J R; Thompson, H; Fraser, M A; Bowden, P E; Day, M J

    2010-05-01

    Epidermolysis bullosa (EB) was diagnosed in eight calves from four farms in the United Kingdom on the basis of clinical, histological and ultrastructural findings. In three affected herds, pedigree Simmental bulls had been mated with Simmental-cross cows. In a fourth herd two Holstein-Friesian calves were affected. Lesions included multifocal erosion and ulceration of the hard and soft palates, tongue, nares and gingiva, with onychomadesis (dysungulation). There was alopecia, erosion and crusting of the coronets, pasterns, fetlocks, carpi, hocks, flanks and axillae. Histopathological findings included segmental separation of full thickness epidermis from the dermis, with formation of large clefts containing eosinophilic fluid, extravasated red blood cells and small numbers of neutrophils. Follicular and interfollicular areas of skin were affected, with clefts extending around hair follicles and sometimes involving whole follicles. Ultrastructurally, there was evidence of vacuolar change within basal keratinocytes, corresponding to areas of histological clefting. Preliminary genetic screening of the candidate keratin genes (bKRT5 and bKRT14) has excluded mutations of these as the cause of this condition.

  1. Epidemiology of inherited epidermolysis bullosa in Romania and genotype-phenotype correlations in patients with dystrophic epidermolysis bullosa.

    PubMed

    Dănescu, S; Has, C; Senila, S; Ungureanu, L; Cosgarea, R

    2015-05-01

    Epidermolysis bullosa (EB) is a rare and so far incurable genetic disease, affecting mainly the skin and mucosal membranes, manifesting with blisters triggered by minor mechanical trauma. Since only few epidemiological data on EB are available, we established a Registry for EB and implemented molecular diagnostic methods. We present epidemiologic data from the EB Registry and genotype-phenotype correlations. In 2006, a registry of patients with EB was initiated in the Department of Dermatology of the University of Medicine, as well as molecular diagnostic tools. The patients were diagnosed on clinical bases, and whenever possible, immunofluorescence mapping and molecular analysis were performed. 89 EB patients were enrolled in the study from 2006 to 2012: 58 patients with dystrophic EB (DEB), 20 with EB simplex, one patient was diagnosed with Kindler syndrome; in 10 patients, the type of EB could not be determined. We have estimated, the total number of EB patients in Romania and we have estimated the incidence and the prevalence of EB. We have also managed to approximate the distribution of EB types in Romania. Moreover, we performed a phenotypic and genotypic characterization in some of the patients included in the EB register. © 2014 European Academy of Dermatology and Venereology.

  2. Malignant melanoma arising in the setting of epidermolysis bullosa simplex: an important distinction from epidermolysis bullosa nevus.

    PubMed

    Hocker, Thomas L; Fox, Matthew C; Kozlow, Jeffrey H; Gonzalez, Joseph V; Shwayder, Tor A; Lowe, Lori; Chan, May P

    2013-10-01

    Patients with epidermolysis bullosa (EB) do not carry a significantly increased risk of melanoma but are prone to developing large, markedly atypical melanocytic nevi (EB nevi), which may mimic melanoma clinically and histologically. Many authors now favor a conservative approach in managing atypical pigmented lesions in patients with EB. We present the case of a 30-year-old woman with severe EB simplex who sought care for a large red and black ulcerated plaque. The clinical differential diagnosis included EB nevus and melanoma. An incisional punch biopsy specimen revealed an atypical melanocytic proliferation with focal florid pagetoid spread and involving elongated rete ridges, consistent with invasive acral lentiginous melanoma. The subsequent amputation was confirmatory. Micrometastasis was detected in 1 of 5 sentinel lymph nodes. To our knowledge, this is the first reported case of melanoma arising in EB simplex-affected skin. It highlights the difficulty in differentiating melanoma from an EB nevus. Despite the increasing awareness of EB nevi, a high index of suspicion for melanoma should be maintained, and early biopsy is recommended when evaluating large pigmented lesions in patients with EB.

  3. Concha bullosa mucocele: A case series and review of the literature

    PubMed Central

    Khalife, Sarah; Marchica, Cinzia; Zawawi, Faisal; Daniel, Sam J.; Manoukian, John J.

    2016-01-01

    Background: Concha bullosa mucocele is a rare diagnosis that presents as a nasal mass. It impinges on surrounding structures and can easily be mistaken for a neoplasm. Objective: The objective of this study was to shed light on this rare entity and report its diagnostic features and treatment outcomes. Methods: A case series conducted in a tertiary health care center. Demographic data, clinical presentation, imaging, cultures, and treatments were recorded. Operative video illustration and key images were obtained. A review of the literature was also performed. Results: A total of five cases were reviewed, four of which were concha bullosa mucoceles and one was a mucopyocele. Three of the patients had some form of previous nasal trauma. Headache and nasal obstruction were the most common symptoms with a nasal mass finding on physical examination. Computed tomography was used in all the patients, and magnetic resonance imaging was used in four of the five patients. Four patients had coexistent chronic rhinosinusitis, and three had positive bacterial cultures. All these patients were treated endoscopically either with middle turbinate marsupialization or subtotal resection. No recurrence has been noted thus far. Conclusion: Concha bullosa mucocele is a rare diagnosis. Imaging characteristics are helpful in considering the diagnosis, although surgical intervention is often necessary to confirm the diagnosis and treat concha bullosa mucocele.

  4. [Hereditary epidermolysis bullosa in school children and adolescents. Clinical picture and interdisciplinary management].

    PubMed

    Ott, H; Eich, C; Schriek, K; Ludwikowski, B

    2016-04-01

    Hereditary epidermolysis bullosa (EB) represents a clinically heterogeneous group of congenital blistering disorders requiring multiprofessional care. EB is associated with a broad spectrum of potentially severe complications often reaching their full extent during school age and adolescence. This review aims at summarizing cutaneous manifestations of EB as well as extracutaneous complications of this complex disease and their interdisciplinary management.

  5. An Incompletely Penetrant Novel Mutation in COL7A1 Causes Epidermolysis Bullosa Pruriginosa and Dominant Dystrophic Epidermolysis Bullosa Phenotypes in an Extended Kindred

    PubMed Central

    Yang, Catherine S; Lu, Yin; Farhi, Anita; Nelson-Williams, Carol; Kashgarian, Michael; Glusac, Earl J; Lifton, Richard P; Antaya, Richard J; Choate, Keith A

    2012-01-01

    Epidermolysis bullosa pruriginosa (EBP) is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by intense pruritus, nodular or lichenoid lesions, and violaceous linear scarring, most prominently on the extensor extremities. Remarkably, identical mutations in COL7A1, which encodes an anchoring fibril protein present at the dermal–epidermal junction, can cause both DEB and EBP with either autosomal dominant or recessive inheritance. We present one family with both dystrophic and pruriginosa phenotypes of epidermolysis bullosa. The proband is a 19-year-old Caucasian woman who initially presented in childhood with lichenoid papules affecting her extensor limbs and intense pruritus consistent with EBP. Her maternal grandmother saw a dermatologist for similar skin lesions that developed without any known triggers at age 47 and mostly resolved spontaneously after approximately 10 years. The proband’s younger brother developed a small crop of pruritic papules on his elbows, dorsal hands, knees, and ankles at age 13. Her second cousin once removed, however, reported a mild blistering disease without pruritus consistent with DEB. Genetic sequencing of the kindred revealed a single dominant novel intron 47 splice site donor G>A mutation, c.4668 + 1 G>A, which we predict leads to exon skipping. Incomplete penetrance is confirmed in her clinically unaffected mother, who carries the same dominant mutation. The wide diversity of clinical phenotypes with one underlying genotype demonstrates that COL7A1 mutations are incompletely penetrant and strongly suggests that other genetic and environmental factors influence clinical presentation. PMID:22515571

  6. An incompletely penetrant novel mutation in COL7A1 causes epidermolysis bullosa pruriginosa and dominant dystrophic epidermolysis bullosa phenotypes in an extended kindred.

    PubMed

    Yang, Catherine S; Lu, Yin; Farhi, Anita; Nelson-Williams, Carol; Kashgarian, Michael; Glusac, Earl J; Lifton, Richard P; Antaya, Richard J; Choate, Keith A

    2012-01-01

    Epidermolysis bullosa pruriginosa (EBP) is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by intense pruritus, nodular or lichenoid lesions, and violaceous linear scarring, most prominently on the extensor extremities. Remarkably, identical mutations in COL7A1, which encodes an anchoring fibril protein present at the dermal-epidermal junction, can cause both DEB and EBP with either autosomal dominant or recessive inheritance. We present one family with both dystrophic and pruriginosa phenotypes of epidermolysis bullosa. The proband is a 19-year-old Caucasian woman who initially presented in childhood with lichenoid papules affecting her extensor limbs and intense pruritus consistent with EBP. Her maternal grandmother saw a dermatologist for similar skin lesions that developed without any known triggers at age 47 and mostly resolved spontaneously after approximately 10 years. The proband's younger brother developed a small crop of pruritic papules on his elbows, dorsal hands, knees, and ankles at age 13. Her second cousin once removed, however, reported a mild blistering disease without pruritus consistent with DEB. Genetic sequencing of the kindred revealed a single dominant novel intron 47 splice site donor G>A mutation, c.4668 + 1 G>A, which we predict leads to exon skipping. Incomplete penetrance is confirmed in her clinically unaffected mother, who carries the same dominant mutation. The wide diversity of clinical phenotypes with one underlying genotype demonstrates that COL7A1 mutations are incompletely penetrant and strongly suggests that other genetic and environmental factors influence clinical presentation. © 2012 Wiley Periodicals, Inc.

  7. Effectiveness of saltwater baths in the treatment of epidermolysis bullosa.

    PubMed

    Petersen, Brian Woodford; Arbuckle, Harvey A; Berman, Stephen

    2015-01-01

    Current management of epidermolysis bullosa (EB) focuses on preventing secondary infections--a leading cause of mortality--by regularly cleaning and bandaging blisters and erosions and preventive bandaging of high-friction areas. Unfortunately the baths and showers used to remove bandages and clean the skin are often painful, causing lack of adherence and subsequent increases in infections, pain, and antimicrobial use. This study evaluates the hypothesis that bathing individuals with EB in saltwater is less painful than in normal bath water. The study also explores whether taking saltwater baths reduces infections as measured through skin pruritus, odor, discharge, and nonbathing pain. Participants recruited from the Children's Hospital Colorado Outpatient EB Clinic completed standardized questionnaires assessing the effects of the clinic's saltwater bathing recommendations; the data were analyzed using frequencies and Fisher tests. After starting saltwater baths, patients reported a significant reduction in pain (91%), pain medication use (66%), skin odor (31%), and skin discharge (44%). No significant differences were found with respect to the type of EB, age, length of time using baths, or amount of salt added. Saltwater baths are a noninvasive, low-cost, effective treatment that significantly reduces bathing pain, pain medication use, and some signs of skin infection. This treatment can be recommended to patients with all studied EB types without regard to age, the specific amount of salt used, bathing frequency, or pain level. Given the central role bathing and dressing changes play in the management of EB, the use of saltwater baths can lead to significant improvement in quality of life.

  8. Altered balance of epidermis-related chemokines in epidermolysis bullosa.

    PubMed

    Ujiie, Inkin; Fujita, Yasuyuki; Nakayama, Chihiro; Matsumura, Wakana; Suzuki, Shotaro; Shinkuma, Satoru; Nomura, Toshifumi; Abe, Riichiro; Shimizu, Hiroshi

    2017-04-01

    Epidermolysis bullosa (EB) is a congenital, refractory skin disease and there are no fundamental treatments. Recently, allogenic cell therapies are beginning to be applied as potential treatments, that are based on the concept that the allogenic cells can migrate into the skin and reconstitute the skin components. Although the mechanisms of cell migration into skin are not fully understood, chemokines are regarded as key factors in recruiting bone marrow-derived cells. Our study aims to elucidate the expression of chemokines in the EB patients. We determined the expression of wound-healing related chemokines in the sera, keratinocytes, and skin tissues of EB patients and compared them to those of healthy volunteers by enzyme-linked immunosorbent assays, quantitative reverse transcription PCR, and immunofluorescence staining. The serum levels of CXCL12 and HMGB1 were found to be significantly elevated in the EB patients. Conversely, the serum levels of CCL21 were found to be lower in the EB patients than in healthy controls. In addition, the serum levels of CXCL12 tended to increase and the serum levels of CCL27 tended to decrease with an increase in the affected body surface areas. To detect the origin of the circulating chemokines, we performed immunofluorescence staining. CCL21, CCL27, HMGB1 and CXCL12 were stained more broadly in the EB patient tissues than those in the control tissues. These results suggest that fluctuations in chemokine levels may contribute in a coordinated way to the wound-healing process and lend clues toward efficient cell therapies for EB. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  9. Recessive dystrophic epidermolysis bullosa results in painful small fibre neuropathy.

    PubMed

    von Bischhoffshausen, Sofia; Ivulic, Dinka; Alvarez, Paola; Schuffeneger, Victor C; Idiaquez, Juan; Fuentes, Constanza; Morande, Pilar; Fuentes, Ignacia; Palisson, Francis; Bennett, David L H; Calvo, Margarita

    2017-03-28

    Small fibres in the skin are vulnerable to damage in metabolic or toxic conditions such as diabetes mellitus or chemotherapy resulting in small fibre neuropathy and associated neuropathic pain. Whether injury to the most distal portion of sensory small fibres due to a primary dermatological disorder can cause neuropathic pain is still unclear. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare condition in which mutations of proteins of the dermo-epidermal junction lead to cycles of blistering followed by regeneration of the skin. Damage is exclusive to the skin and mucous membranes, with no known direct compromise of the nervous system. It is increasingly recognized that most RDEB patients experience daily pain, the aetiology of which is unclear but may include inflammation (in the wounds), musculoskeletal (due to atrophy and retraction scars limiting movement) or neuropathic pain. In this study we investigated the incidence of neuropathic pain and examined the presence of nerve dysfunction in RDEB patients. Around three quarters of patients presented with pain of neuropathic characteristics, which had a length-dependent distribution. Quantitative sensory testing of the foot revealed striking impairments in thermal detection thresholds combined with an increased mechanical pain sensitivity and wind up ratio (temporal summation of noxious mechanical stimuli). Nerve conduction studies showed normal large fibre sensory and motor nerve conduction; however, skin biopsy showed a significant decrease in intraepidermal nerve fibre density. Autonomic nervous system testing revealed no abnormalities in heart rate and blood pressure variability however the sympathetic skin response of the foot was impaired and sweat gland innervation was reduced. We conclude that chronic cutaneous injury can lead to injury and dysfunction of the most distal part of small sensory fibres in a length-dependent distribution resulting in disabling neuropathic pain. These findings also

  10. The genetic basis of epidermolysis bullosa simplex with mottled pigmentation.

    PubMed Central

    Uttam, J; Hutton, E; Coulombe, P A; Anton-Lamprecht, I; Yu, Q C; Gedde-Dahl, T; Fine, J D; Fuchs, E

    1996-01-01

    Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant skin diseases characterized by blistering, due to mechanical stress-induced degeneration of basal epidermal cells. It is now well-established that the three major subtypes of EBS are genetic disorders of the basal epidermal keratins, keratin 5 (K5) and keratin 14 (K14). Here we show that a rare subtype, referred to as EBS with mottled pigmentation (MP), is also a disorder of these keratins. Affected members of two seemingly unrelated families with EBS-MP had a C to T point mutation in the second base position of codon 24 of one of two K5 alleles, leading to a Pro: Leu mutation. This mutation was not present in unaffected members nor in 100 alleles from normal individuals. Linkage analyses mapped the defect to this type II keratin gene (peak logarithm of odds score at phi = 0 of 3.9), which is located on chromosome 12q11-q13. This provides strong evidence that this mutation is responsible for the EBS-MP phenotype. Only conserved between K5 and K6, and not among any of the other type II keratins, Pro-24 is in the nonhelical head domain of K5, and only mildly perturbs the length of 10-nm keratin filaments assembled in vitro. However, this part of the K5 head domain is likely to protrude on the filament surface, perhaps leading to additional aberrations in intermediate filament architecture and/or in melanosome distribution that are seen ultrastructurally in patients with the mutation. Images Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8799157

  11. Recessive dystrophic epidermolysis bullosa results in painful small fibre neuropathy

    PubMed Central

    von Bischhoffshausen, Sofia; Ivulic, Dinka; Alvarez, Paola; Schuffeneger, Victor C.; Idiaquez, Juan; Fuentes, Constanza; Morande, Pilar; Fuentes, Ignacia; Palisson, Francis; Calvo, Margarita

    2017-01-01

    Small fibres in the skin are vulnerable to damage in metabolic or toxic conditions such as diabetes mellitus or chemotherapy resulting in small fibre neuropathy and associated neuropathic pain. Whether injury to the most distal portion of sensory small fibres due to a primary dermatological disorder can cause neuropathic pain is still unclear. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare condition in which mutations of proteins of the dermo-epidermal junction lead to cycles of blistering followed by regeneration of the skin. Damage is exclusive to the skin and mucous membranes, with no known direct compromise of the nervous system. It is increasingly recognized that most RDEB patients experience daily pain, the aetiology of which is unclear but may include inflammation (in the wounds), musculoskeletal (due to atrophy and retraction scars limiting movement) or neuropathic pain. In this study we investigated the incidence of neuropathic pain and examined the presence of nerve dysfunction in RDEB patients. Around three quarters of patients presented with pain of neuropathic characteristics, which had a length-dependent distribution. Quantitative sensory testing of the foot revealed striking impairments in thermal detection thresholds combined with an increased mechanical pain sensitivity and wind up ratio (temporal summation of noxious mechanical stimuli). Nerve conduction studies showed normal large fibre sensory and motor nerve conduction; however, skin biopsy showed a significant decrease in intraepidermal nerve fibre density. Autonomic nervous system testing revealed no abnormalities in heart rate and blood pressure variability however the sympathetic skin response of the foot was impaired and sweat gland innervation was reduced. We conclude that chronic cutaneous injury can lead to injury and dysfunction of the most distal part of small sensory fibres in a length-dependent distribution resulting in disabling neuropathic pain. These findings also

  12. An Evaluation of Treatments for Pruritus in Epidermolysis Bullosa

    PubMed Central

    Danial, Christina; Adeduntan, Rasidat; Gorell, Emily S.; Lucky, Anne W.; Paller, Amy S.; Bruckner, Anna L.; Pope, Elena; Morel, Kimberly D.; Levy, Moise L.; Li, Shufeng; Gilmore, Elaine S.; Lane, Alfred T

    2016-01-01

    Background Pruritus is a common complication in patients with epidermolysis bullosa (EB) and can be problematic. Objective data about the treatments used by EB patients for pruritus have not been reported and recommendations are limited. Objective To quantitatively determine which treatments have been used by EB patients for pruritus and to evaluate the perceived effectiveness of these treatments in pruritus relief. Methods A questionnaire was developed to evaluate which treatments and therapies have been used for pruritus in patients of all ages and types of EB. Questions about bathing products, moisturizers, topical products, oral medications, dressings, and alternative therapies were included. A 5-point Likert scale (-2=relieves itch a lot, -1=relieves itch a little, 0=no change, 1=increases itch a little, 2=increases itch a lot) was used to evaluate the perceived effectiveness of different treatments on pruritus relief. Patients from seven North American EB centers were invited to participate. Results Greasy ointments (53.4%), lotions (45.2%), creams (40.4%), and oral hydroxyzine (39.0%) were the most frequently used treatments for pruritus. Treatments that were used frequently and perceived to be the most effective included creams (mean=-1.1), topical prescription corticosteroids (mean=-1.0), oils (mean=-0.9), oral hydroxyzine (mean=-0.9), topical diphenhydramine (mean=-0.9), and vaporizing rub (menthol/camphor/eucalyptus) (mean=-0.9). Patients that used creams (p=0.05) or lotions (p=0.04) more often experienced significantly less pruritus. Systemic opioids (mean=0.3), adherent bandages (mean=0.3), and bleach baths (mean=0.2) slightly increased pruritus. Conclusions Randomized-controlled trials of therapies will be necessary to develop evidence-based recommendations for control of pruritus in EB patients. PMID:25557557

  13. Evaluation of Treatments for Pruritus in Epidermolysis Bullosa.

    PubMed

    Danial, Christina; Adeduntan, Rasidat; Gorell, Emily S; Lucky, Anne W; Paller, Amy S; Bruckner, Anna L; Pope, Elena; Morel, Kimberly D; Levy, Moise L; Li, Shufeng; Gilmore, Elaine S; Lane, Alfred T

    2015-01-01

    Pruritus is a common complication in patients with epidermolysis bullosa (EB). There is limited published data about the treatments that individuals with EB use for pruritus. The objective of the current study was to determine quantitatively which treatments individuals with EB have used for pruritus and to evaluate the perceived effectiveness of these treatments in pruritus relief. A questionnaire was developed to evaluate the treatments and therapies used for pruritus in patients of all ages and for all types of EB. Questions about bathing products, moisturizers, topical products, oral medications, dressings, and alternative therapies were included. A 5-point Likert scale (-2 = relieves itch a lot, -1 = relieves itch a little, 0 = no change, 1 = increases itch a little, 2 = increases itch a lot) was used to evaluate perceived effectiveness. Patients from seven North American EB centers were invited to participate. Greasy ointments (53.4%), lotions (45.2%), creams (40.4%), and oral hydroxyzine (39.0%) were the most frequently used treatments for pruritus. Treatments that were used frequently and perceived to be the most effective included creams (mean = -1.1), topical prescription corticosteroids (mean = -1.0), oils (mean = -0.9), oral hydroxyzine (mean = -0.9), topical diphenhydramine (mean = -0.9), and vaporizing rub (menthol, camphor, eucalyptus) (mean = -0.9). Systemic opioids (mean = 0.3), adherent bandages (mean = 0.3), and bleach baths (mean = 0.2) slightly increased pruritus. Randomized controlled trials of therapies will be necessary to develop evidence-based recommendations for control of pruritus in individuals with EB.

  14. Multicentre consensus recommendations for skin care in inherited epidermolysis bullosa.

    PubMed

    El Hachem, May; Zambruno, Giovanna; Bourdon-Lanoy, Eva; Ciasulli, Annalisa; Buisson, Christiane; Hadj-Rabia, Smail; Diociaiuti, Andrea; Gouveia, Carolina F; Hernández-Martín, Angela; de Lucas Laguna, Raul; Dolenc-Voljč, Mateja; Tadini, Gianluca; Salvatori, Guglielmo; De Ranieri, Cristiana; Leclerc-Mercier, Stephanie; Bodemer, Christine

    2014-05-20

    Inherited epidermolysis bullosa (EB) comprises a highly heterogeneous group of rare diseases characterized by fragility and blistering of skin and mucous membranes. Clinical features combined with immunofluorescence antigen mapping and/or electron microscopy examination of a skin biopsy allow to define the EB type and subtype. Molecular diagnosis is nowadays feasible in all EB subtypes and required for prenatal diagnosis. The extent of skin and mucosal lesions varies greatly depending on EB subtype and patient age. In the more severe EB subtypes lifelong generalized blistering, chronic ulcerations and scarring sequelae lead to multiorgan involvement, major morbidity and life-threatening complications. In the absence of a cure, patient management remains based on preventive measures, together with symptomatic treatment of cutaneous and extracutaneous manifestations and complications. The rarity and complexity of EB challenge its appropriate care. Thus, the aim of the present study has been to generate multicentre, multidisciplinary recommendations on global skin care addressed to physicians, nurses and other health professionals dealing with EB, both in centres of expertise and primary care setting. Almost no controlled trials for EB treatment have been performed to date. For this reason, recommendations were prepared by a multidisciplinary team of experts from different European EB centres based on available literature and expert opinion. They have been subsequently revised by a panel of external experts, using an online-modified Delphi method to generate consensus. Recommendations are reported according to the age of the patients. The major topics treated comprise the multidisciplinary approach to EB patients, global skin care including wound care, management of itching and pain, and early diagnosis of squamous cell carcinoma. Aspects of therapeutic patient education, care of disease burden and continuity of care are also developed. The recommendations are

  15. The successful use of extracorporeal photopheresis in a 12-year-old patient with refractory epidermolysis bullosa acquisita.

    PubMed

    Liszewski, Walter; Omland, Silje Haukali; Gniadecki, Robert

    2015-01-01

    Epidermolysis bullosa acquisita is a rare autoimmune bullous disease of the mucosa and skin characterized by the presence of anti-collagen VII antibodies at the dermoepidermal junction. Most patients respond to immunosuppressive or antiinflammatory agents, although patients whose condition is refractory to these therapies will require more aggressive treatment. We present a 12-year-old girl with refractory epidermolysis bullosa acquisita who responded to extracorporeal photopheresis. © 2015 Wiley Periodicals, Inc.

  16. 506U78 in Treating Patients With Lymphoma

    ClinicalTrials.gov

    2013-01-15

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Small Intestine Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome

  17. Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma

    ClinicalTrials.gov

    2017-09-28

    Follicular Variant Peripheral T-Cell Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Stage IB Mycosis Fungoides; Stage II Mycosis Fungoides; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides

  18. Serological diagnosis of allergic bronchopulmonary mycosis: Progress and challenges.

    PubMed

    Fukutomi, Yuma; Tanimoto, Hidenori; Yasueda, Hiroshi; Taniguchi, Masami

    2016-01-01

    Prompt diagnosis of allergic bronchopulmonary mycosis (ABPM) is an important clinical issue in preventing irreversible lung damage. Therefore, a good serological marker for the diagnosis of ABPM is desired in clinical practice. The measurement of IgE antibody to crude Aspergillus fumigatus allergen is considered the first step in screening asthmatic patients for allergic bronchopulmonary aspergillosis (ABPA). However, presence of IgE to A. fumigatus does not always indicate genuine sensitization to A. fumigatus because of cross-reactivity between crude extracts from different fungal sources. The application of molecular-based allergy diagnosis can solve this problem. The specificity of testing can be greatly improved by measuring the IgE antibody to Asp f 1 and f 2, specific allergen components for genuine A. fumigatus allergy. The problem of cross-reactivity between crude fungal extracts is also true for the identification of genuine causal fungi in each ABPM patient. Some patients with ABPM induced by fungi other than Aspergillus may be consistent with ABPA diagnostic criteria because current criteria depend on IgE/IgG reactivity to crude extracts. Accurate identification of genuine causal fungi for ABPM is of clinical importance, considering that clinical presentation, anti-fungal treatment strategies and disease prognosis can be influenced by different causal fungi. The diagnosis of causal fungi can be robustly validated by the confirmation of genuine sensitization to fungi after measuring IgE to specific allergen components, as well as repeated microbiological isolation of the fungi from their airway.

  19. [Epidemiological aspects of mycosis in the critical patient].

    PubMed

    Pemán Garcia, J

    2008-01-01

    Fungemia, generally causes by Candida spp., is the most frequent deep mycoses in the critical patient and is many times clinically undistinguishable from bacterial septicemia. Less frequently, respiratory or disseminated mycosis produced by Aspergillus or other filamentous fungi, such as Scedosporium, Fusarium, Pneumocystis, Acremonium or zygomycetes have been described. Currently, invasive candidiasis is the fourth cause of nosocomial infection in Europe and the USA. Furthermore, in the SCOPE study, Candida is the third microorganism isolated from the blood culture in the ICU and the mortality that can be attributed to it reaches 25 %-38 %. Currently, the incidence of candidemia has been estimated to be 2 cases per every 1,000 admissions in the mixed critical units and 9.9 cases in the critical surgical units. On its part, invasive aspergillosis is observed in 1.25 % of the patients admitted to the ICU and mostly affects patients with chronic bronchopathy treated with glucocorticoids. It is considered as an indicator of bad prognosis and is associated to very high mortality rates (40 %-100 %).

  20. Cerebral mycosis: 7-year retrospective series in a tertiary center.

    PubMed

    Raparia, Kirtee; Powell, Suzanne Z; Cernoch, Pat; Takei, Hidehiro

    2010-06-01

    This study focuses on the epidemiology, clinical manifestations, risk factors, diagnosis and outcome of all cases of central nervous system (CNS) fungal infections in a tertiary center. Medical records of 18 patients of culture-proven CNS fungal infections were retrospectively reviewed from 2000 to 2007, including 12 isolated from the cerebrospinal fluid (CSF) and seven from tissue biopsy. Patient demographic data included 10 males and eight females. The mean age was 55 years (range: 24-89 years). All but one patient were immunocompromised. Fungal organisms isolated from CSF included: Cryptococcous neoformans (8 patients), Coccidioides immitis (3 patients), and Aspergillus versicolor (1 patient). Histopathology of seven biopsy cases revealed groups of pigmented golden-brown fungal forms in three cases; three cases showed septate fungi, two of which had melanin in their walls; and one case showed multiple round spherules. These cases on microbiological cultures grew Coccidioides immitis (1 patient), Aspergillus fumigatus (1 patient), Cladophialophora bantiana (2 patients), Fonsecaea monophora (1 patient) and Scedosporium apiospermum (2 patients). Five of the seven fungal organisms isolated from tissue biopsies were dematiaceous fungi. Twelve patients died after a period of a few weeks to months, two were lost to follow-up, and four are alive with severe neurological sequelae. CNS fungal infections in our cohort were more common in patients post-transplant and with hematologic malignancies. In our series, rare dematiaceous fungi are emerging agents for cerebral mycosis. The outcome of CNS fungal infections is poor despite vigorous antifungal therapy.

  1. Left ventricular non-compaction cardiomyopathy associated with epidermolysis bullosa simplex with muscular dystrophy and PLEC1 mutation.

    PubMed

    Villa, Chet R; Ryan, Thomas D; Collins, James J; Taylor, Michael D; Lucky, Anne W; Jefferies, John L

    2015-02-01

    Plectin mutations have been reported in epidermolysis bullosa simplex with muscular dystrophy. We report the first case of left ventricular non-compaction in an 18-year-old male with epidermolysis bullosa simplex with muscular dystrophy. The patient was diagnosed with epidermolysis bullosa simplex after blistering was noted at birth. Motor function difficulties were first recognized at age 11, however the patient was lost to follow up. He was re-evaluated at age 17 and demonstrated significant ptosis, ophthalmoparesis, and pharyngeal muscle weakness. He had predominant proximal muscle weakness with the inability to raise arms against gravity. He was ambulatory for short distances but lost the ability to rise from the floor at 14 years. He was subsequently diagnosed with epidermyolysis bullosa simplex with muscular dystrophy and a PLEC1 mutation. Screening cardiovascular imaging revealed a diagnosis of isolated left ventricular non-compaction. This case highlights the potential for delayed onset muscular dystrophy in patients with epidermolysis bullosa simplex. Furthermore, this case also underscores the importance of long term, routine cardiac evaluation, including imaging and electrophysiologic evaluation, in patients with epidermolysis bullosa simplex with muscular dystrophy as the cardiac phenotype appears to parallel the variable severity and age of onset that characterize the neuromuscular phenotype. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Multicentre consensus recommendations for skin care in inherited epidermolysis bullosa

    PubMed Central

    2014-01-01

    Background Inherited epidermolysis bullosa (EB) comprises a highly heterogeneous group of rare diseases characterized by fragility and blistering of skin and mucous membranes. Clinical features combined with immunofluorescence antigen mapping and/or electron microscopy examination of a skin biopsy allow to define the EB type and subtype. Molecular diagnosis is nowadays feasible in all EB subtypes and required for prenatal diagnosis. The extent of skin and mucosal lesions varies greatly depending on EB subtype and patient age. In the more severe EB subtypes lifelong generalized blistering, chronic ulcerations and scarring sequelae lead to multiorgan involvement, major morbidity and life-threatening complications. In the absence of a cure, patient management remains based on preventive measures, together with symptomatic treatment of cutaneous and extracutaneous manifestations and complications. The rarity and complexity of EB challenge its appropriate care. Thus, the aim of the present study has been to generate multicentre, multidisciplinary recommendations on global skin care addressed to physicians, nurses and other health professionals dealing with EB, both in centres of expertise and primary care setting. Methods Almost no controlled trials for EB treatment have been performed to date. For this reason, recommendations were prepared by a multidisciplinary team of experts from different European EB centres based on available literature and expert opinion. They have been subsequently revised by a panel of external experts, using an online-modified Delphi method to generate consensus. Results Recommendations are reported according to the age of the patients. The major topics treated comprise the multidisciplinary approach to EB patients, global skin care including wound care, management of itching and pain, and early diagnosis of squamous cell carcinoma. Aspects of therapeutic patient education, care of disease burden and continuity of care are also developed

  3. Antifungal Therapy for Systemic Mycosis and the Nanobiotechnology Era: Improving Efficacy, Biodistribution and Toxicity

    PubMed Central

    Souza, Ana C. O.; Amaral, Andre C.

    2017-01-01

    Fungal diseases have been emerging as an important public health problem worldwide with the increase in host predisposition factors due to immunological dysregulations, immunosuppressive and/or anticancer therapy. Antifungal therapy for systemic mycosis is limited, most of times expensive and causes important toxic effects. Nanotechnology has become an interesting strategy to improve efficacy of traditional antifungal drugs, which allows lower toxicity, better biodistribution, and drug targeting, with promising results in vitro and in vivo. In this review, we provide a discussion about conventional antifungal and nanoantifungal therapies for systemic mycosis. PMID:28326065

  4. Toxic Epidermal Necrolysis in Recessive Dystrophic Epidermolysis Bullosa following Bone Marrow Transplantation.

    PubMed

    Boull, Christina L; Hylwa, Sara A; Sajic, Dusan; Wagner, John E; Tolar, Jakub; Hook, Kristen P

    2016-06-01

    A 3-year-old child with recessive dystrophic epidermolysis bullosa treated with bone marrow transplantation subsequently developed body-wide epidermal detachment distinct from his epidermolysis bullosa. Toxic epidermal necrolysis was diagnosed by examination and skin biopsy. Although graft-vs-host disease was considered, he had no features of this diagnosis by laboratory studies or skin biopsy, and he improved without addition of further immune suppressants. Throughout the episode, the patient was maintained on cyclosporine A, a component of his transplant regimen, and also a reported therapy for toxic epidermal necrolysis. He had full recovery. Re-epithelialization occurred in a unique folliculocentric pattern, which we postulate was related to the patient's mesenchymal stem cell infusion, received as an adjunct to his marrow transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Study of relationship of concha bullosa to nasal septal deviation and sinusitis.

    PubMed

    Bhandary, Satheesh Kumar; Kamath P, Shrinath D

    2009-09-01

    To study the etiological role of concha bollosa in deviated nasal septum (DNS) and sinusitis. In this retrospective study 419 consecutive CT scans of paranasal sinuses done between October 2005 and September 2007 were serially evaluated for the presence of concha, DNS and sinusitis. Out of 419 CT scans evaluated, concha bullosa was present in 40.3% of patients. Among these, concha co-existent DNS was found in 87.5%, air column between DNS and concha was found in 88.5% and sinus disease was present in 69.2% of patients. Presence of air column between DNS and concha excludes the etiological role of concha in DNS. Concha bullosa may predispose to sinusitis.

  6. Management of a pediatric patient with epidermolysis bullosa receiving comprehensive dental treatment under general anesthesia.

    PubMed

    Yoon, Richard K; Ohkawa, Susumu

    2012-01-01

    The purpose of this report was to detail clinical considerations and a general anesthetic approach for a 3-year-old pediatric dental patient with epidermolysis bullosa, a group of rare genetic disorders characterized by blister development following minor trauma or traction to the skin or mucosal surfaces. Challenges in providing comprehensive dental treatment and care under general anesthesia are discussed. Early evaluation is vital to preventing the consequences of severe early childhood caries.

  7. Occurrence of epidermolysis bullosa along with Amelogenesis imperfecta in female patient of India.

    PubMed

    Javed, A P; Shenai, Prashanth; Chatra, Laxmikanth; Veena, K M; Rao, Prasanna Kumar; Prabhu, Rachana

    2013-11-01

    Epidermolysis bullosa (EB) is an inherited disorder, which is characteristically presented as skin blisters developing in response to minor injury. Junctional variety of EB is also associated with enamel hypoplasia. Amelogenesis imperfecta presents with abnormal formation of the enamel both in deciduous and permanent dentition. This article describes a previously unreported case of Amelogenesis imperfecta with complete loss of enamel in a young female patient with EB.

  8. [Epidermolysis bullosa simplex congenital antenatal discovery and contribution of 3D ultrasound].

    PubMed

    Wylomanski, S; Camp, G; Philippe, H J; Le Vaillant, C

    2014-06-01

    Epidermolysis bullosa (EB) comprises a heterogeneous group of genodermatoses whose prognosis is variable. The diagnosis is suggested by prenatal ultrasound at signs, especially for junctional EB with pyloric atresia. The authors report a case of antenatal image limited skin undermining highlighted by the ultrasound three-dimensional (3D) in connection with a diagnosis of a congenital epidermolysis simplex confirmed postnatal period. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. A nonsense mutation in the COL7A1 gene causes epidermolysis bullosa in Vorderwald cattle.

    PubMed

    Pausch, Hubert; Ammermüller, Simon; Wurmser, Christine; Hamann, Henning; Tetens, Jens; Drögemüller, Cord; Fries, Ruedi

    2016-12-01

    The widespread use of individual sires for artificial insemination promotes the propagation of recessive conditions. Inadvertent matings between unnoticed carriers of deleterious alleles may result in the manifestation of fatal phenotypes in their progeny. Breeding consultants and farmers reported on Vorderwald calves with a congenital skin disease. The clinical findings in affected calves were compatible with epidermolysis bullosa. Pedigree analysis indicated autosomal recessive inheritance of epidermolysis bullosa in Vorderwald cattle. We genotyped two diseased and 41 healthy animals at 41,436 single nucleotide polymorphisms and performed whole-genome haplotype-based association testing, which allowed us to map the locus responsible for the skin disease to the distal end of bovine chromosome 22 (P = 8.0 × 10(-14)). The analysis of whole-genome re-sequencing data of one diseased calf, three obligate mutation carriers and 1682 healthy animals from various bovine breeds revealed a nonsense mutation (rs876174537, p.Arg1588X) in the COL7A1 gene that segregates with the disease. The same mutation was previously detected in three calves with dystrophic epidermolysis bullosa from the Rotes Höhenvieh cattle breed. We show that diseased animals from Vorderwald and Rotes Höhenvieh cattle are identical by descent for an 8.72 Mb haplotype encompassing rs876174537 indicating they inherited the deleterious allele from a recent common ancestor. Autosomal recessive epidermolysis bullosa in Vorderwald and Rotes Höhenvieh cattle is caused by a nonsense mutation in the COL7A1 gene. Our findings demonstrate that deleterious alleles may segregate across cattle populations without apparent admixture. The identification of the causal mutation now enables the reliable detection of carrier animals. Genome-based mating strategies can avoid inadvertent matings of carrier animals thereby preventing the birth of homozygous calves that suffer from a painful skin disease.

  10. Inflammatory epidermolysis bullosa acquisita in a 4-year-old girl.

    PubMed

    Lazić-Mosler, Elvira; Jukić, Ines Lakoš; Murat-Sušić, Slobodna; Husar, Karmela; Skerlev, Mihael; Bukvić Mokos, Zrinka; Ishii, Norito; Hashimoto, Takashi; Marinović, Branka

    2015-11-01

    This study presents a case of linear immunoglobulin A dermatosis-like epidermolysis bullosa acquisita in a 4-year-old girl showing rapid, widespread and inflammatory skin lesions. The diagnosis was confirmed by histopathology, direct and indirect immunofluorescence, various immunoblotting analyses and enzyme-linked immunosorbent assays. Despite the severe clinical manifestations, the disease was successfully controlled by combination therapy of oral prednisolone and dapsone. © 2015 Japanese Dermatological Association.

  11. Urological surgery in epidermolysis bullosa: tactical planning for surgery and anesthesia.

    PubMed

    Jesus, Lisieux Eyer de; Rangel, Maira; Moura-Filho, Ronaldo S; Novaes, Glória; Quattrino, Ada; Aguas, Angelica F

    2014-01-01

    Epidermolysis bullosa (EB) is characterized by extreme fragility of the skin and mucosae. Anesthetic and surgical techniques have to be adapted to those children and routine practice may not be adequate. Urological problems are relatively common, but surgical techniques adapted to those children have not been well debated and only low evidence is available to this moment. Herein we discuss the specifics of anesthetic and surgical techniques chosen to treat a six year old EB male presenting with symptomatic phimosis.

  12. Primary amenorrhoea due to a rare cause: epidermolysis bullosa causing haematometra.

    PubMed

    Singh, Chanchal; Tripathi, Reva; Sardana, Kabir; Mala, Yedla Manikya

    2013-01-02

    A 27-year-old woman with junctional epidermolysis bullosa (EB) presented with primary amenorrhoea and massive haematometra. Considering her severe physical handicap and anticipated problems in optimising menstrual hygiene, the patient and her parents opted for hysterectomy which was performed uneventfully. The patient was recovering well postoperatively until the eighth postoperative day when she developed acute dilation of stomach and unfortunately died on day 17.

  13. Diffuse Partial Woolly Hair in a Patient with Epidermolysis Bullosa Simplex with Mottled Pigmentation

    PubMed Central

    Gerkowicz, Agnieszka; Trüeb, Ralph M

    2014-01-01

    Diffuse partial woolly hair (DPWH) is an uncommon pilar dysplasia defined by the presence of two hair shaft populations with wooly hairs distributed diffusely among normal hairs throughout the scalp. So far the condition has been reported as an isolated disorder with familial occurrence. We report a case of DPWH in 35-year-old female patient with epidermolysis bullosa with mottled pigmentation. PMID:25191045

  14. Gene therapy: pursuing restoration of dermal adhesion in recessive dystrophic epidermolysis bullosa.

    PubMed

    Cutlar, Lara; Greiser, Udo; Wang, Wenxin

    2014-01-01

    The replacement of a defective gene with a fully functional copy is the goal of the most basic gene therapy. Recessive dystrophic epidermolysis bullosa (RDEB) is characterised by a lack of adhesion of the epidermis to the dermis. It is an ideal target for gene therapy as all variants of hereditary RDEB are caused by mutations in a single gene, COL7A1, coding for type VII collagen, a key component of anchoring fibrils that secure attachment of the epidermis to the dermis. RDEB is one of the most severe variants in the epidermolysis bullosa (EB) group of heritable skin diseases. Epidermolysis bullosa is defined by chronic fragility and blistering of the skin and mucous membranes due to mutations in the genes responsible for production of the basement membrane proteins. This condition has a high personal, medical and socio-economic impact. People with RDEB require a broad spectrum of medications and specialised care. Due to this being a systemic condition, most research focus is in the area of gene therapy. Recently, preclinical works have begun to show promise. They focus on the virally mediated ex vivo correction of autologous epithelium. These corrected cells are then to be expanded and grafted onto the patient following the lead of the first successful gene therapy in dermatology being a grafting of corrected tissue for junctional EB treatment. Current progress, outstanding challenges and future directions in translating these approaches in clinics are reviewed in this article.

  15. Inpatient management of children with recessive dystrophic epidermolysis bullosa: A review.

    PubMed

    Li, Alvin W; Prindaville, Brea; Bateman, Scot T; Gibson, Timothy E; Wiss, Karen

    2017-09-25

    Recessive dystrophic epidermolysis bullosa is a disorder marked by skin and mucosal blistering after minimal trauma. Even the most routine procedures in the hospital, if done incorrectly, can precipitate extensive skin loss, pain, and scarring. Most providers have little experience working with patients with this degree of skin fragility. When a person with recessive dystrophic epidermolysis bullosa is admitted to the hospital, there are multiple considerations to keep in mind while strategizing an effective care plan: avoidance of new blisters with a "hands-off" approach; careful consideration of all indwelling devices; symptomatic management of pain, itch, and anxiety; coordination of dressing changes; aggressive treatment of skin infections; environmental and staffing considerations; and awareness of other chronic complications that affect care, such as anemia, malnutrition, and chronic pain. To minimize discomfort for patients with recessive dystrophic epidermolysis bullosa during the hospital stay, inpatient care teams should understand these considerations and modify the care plan accordingly. Prior preparation by the hospital facility and inpatient care team will facilitate the delivery of safe and effective care and greatly improve the overall patient experience. © 2017 Wiley Periodicals, Inc.

  16. Successful forearm prosthesis fitting in a patient with epidermolysis bullosa dystrophica: Case report.

    PubMed

    Verduyn, Carl; Morren, Marie-Anne; Stas, Marguerite; Sinnaeve, Friedl; Segers, Katarina; Kiekens, Carlotte

    2017-07-01

    Epidermolysis bullosa dystrophica is a rare dermatological disease characterized by extreme skin fragility and elevated risk of developing a squamous cell carcinoma. In some cases, amputation of a limb is necessary. Case description and methods: A 37-year-old man with recessive, severe generalized epidermolysis bullosa dystrophica developed a squamous cell carcinoma on the right forearm requiring a below-elbow amputation. Preoperative advice concerning indication and level of amputation was given. Due to potential skin problems, a conventional prosthesis was not feasible. Findings and outcomes: A custom-designed adaptive prosthesis with an upper arm cuff was trialed and was well tolerated. Multiple working tools, attached with a rotation and inclination system, allowed independence and return to work. Despite multiple potential skin problems of the stump, the patient was successfully fitted with a custom-designed adaptive prosthesis. Preparation for this fitting was done by a comprehensive multidisciplinary patient-centered approach. Clinical relevance Despite severe skin fragility, a patient with epidermolysis bullosa dystrophica was successfully fitted with a custom-designed adaptive upper limb prosthesis allowing good functional outcome. This required a multidisciplinary and patient-centered approach.

  17. Pseudosyndactyly - an inflammatory and fibrotic wound healing disorder in recessive dystrophic epidermolysis bullosa.

    PubMed

    Breitenbach, Jenny; Gruber, Christina; Klausegger, Alfred; Trost, Andrea; Bogner, Barbara; Reitsamer, Herbert; Bauer, Johann W

    2015-12-01

    A genetic blistering skin disease, recessive dystrophic epidermolysis bullosa (RDEB), is marked by severe wound healing defects and finger contractures. The purpose of this investigation was to elucidate the mechanisms of impaired wound healing and pseudosyndactyly occurring in RDEB patients by studying the role of known inflammation and fibrosis markers in RDEB pseudosyndactyly tissue. We studied the expression of the fibrosis and/or inflammation markers tenascin-C, α-smooth muscle actin, transforming growth factor-β1, interleukin-1β, and interleukin-6 in scarring and nonscarring tissue from healthy donors and RDEB patients by semiquantitative real time-PCR and, where applicable, by immunoblots. Furthermore, the distribution pattern of α-smooth muscle actin and tenascin-C were assessed by immunofluorescence microscopy. Based on mRNA and protein analysis, we found upregulation of tenascin-C, interleukin-1β, and interleukin-6 - but not of transforming growth factor-β1 - in recessive dystrophic epidermolysis bullosa scar samples taken from pseudosyndactyly hands. Unexpectedly, α-smooth muscle actin was not upregulated. Our results confirm inflammation and fibrosis in recessive dystrophic epidermolysis bullosa, especially in scars, suggesting major roles for these processes in pseudosyndactyly. Our data therefore suggests the potential use of antiinflammatory and antifibrotic drugs in the prevention of pseudosyndactyly. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  18. MMP-9 and CXCL8/IL-8 Are Potential Therapeutic Targets in Epidermolysis Bullosa Simplex

    PubMed Central

    Lettner, Thomas; Lang, Roland; Klausegger, Alfred; Hainzl, Stefan

    2013-01-01

    Epidermolysis bullosa refers to a group of genodermatoses that affects the integrity of epithelial layers, phenotypically resulting in severe skin blistering. Dowling-Meara, the major subtype of epidermolysis bullosa simplex, is inherited in an autosomal dominant manner and can be caused by mutations in either the keratin-5 (K5) or the keratin-14 (K14) gene. Currently, no therapeutic approach is known, and the main objective of this study was to identify novel therapeutic targets. We used microarray analysis, semi-quantitative real-time PCR, western blot and ELISA to identify differentially regulated genes in two K14 mutant cell lines carrying the mutations K14 R125P and K14 R125H, respectively. We found kallikrein-related peptidases and matrix metalloproteinases to be upregulated. We also found elevated expression of chemokines, and we observed deregulation of the Cdc42 pathway as well as aberrant expression of cytokeratins and junction proteins. We further demonstrated, that expression of these genes is dependent on interleukin-1 β signaling. To evaluate these data in vivo we analysed the blister fluids of epidermolysis bullosa simplex patients vs. healthy controls and identified matrix metalloproteinase-9 and the chemokine CXCL8/IL-8 as potential therapeutic targets. PMID:23894602

  19. Main problems experienced by children with epidermolysis bullosa: a qualitative study with semi-structured interviews.

    PubMed

    van Scheppingen, Corinne; Lettinga, Ant T; Duipmans, José C; Maathuis, Carel G B; Jonkman, Marcel F

    2008-01-01

    The objective of this study was to identify and specify the problems of children with epidermolysis bullosa. The questions explored were: (i) What do children with epidermolysis bullosa experience as the most difficult problems; (ii) What is the impact of these problems on their daily life; and (iii) Do these experiences differ between mildly and severely affected children? Qualitative research methodology was used, comprising a series of semi-structured interviews with children with different (sub)types of epidermolysis bullosa. The interviews were analysed systematically with help of the qualitative software package Atlas-ti. Five main themes were found: (i) having an itchy skin, (ii) being in pain, (iii) having difficulties with participation, (iv) lack of understanding of others, and (v) the feeling of being different. Severely affected children suffered most from itch and treatment-related pain. Mildly affected children had more problems with activity-related pain. Mildly affected children also had more concerns about their appearance and the teasing and staring of others than did severely affected children. Both groups had difficulties with participation, the visibility of their disease and the feeling of being different.

  20. Invasive mycosis due to species of Blastobotrys in immunocompromised patients with reduced susceptibility to antifungals.

    PubMed

    Kumar, Anil; Babu, Rachana; Bijulal, Swapna; Abraham, Mohan; Sasidharan, P; Kathuria, Shallu; Sharma, Cheshta; Meis, Jacques F; Chowdhary, Anuradha

    2014-11-01

    Cases of invasive mycosis due to Blastobotrys serpentis and B. proliferans identified by sequencing in a preterm patient and a rhabdomyosarcoma patient, respectively, are reported. Both species revealed elevated fluconazole and echinocandin MICs by the CLSI broth microdilution method. Additionally, B. serpentis exhibited high amphotericin B MICs, thus posing serious therapeutic challenges.

  1. Invasive Mycosis Due to Species of Blastobotrys in Immunocompromised Patients with Reduced Susceptibility to Antifungals

    PubMed Central

    Kumar, Anil; Babu, Rachana; Bijulal, Swapna; Abraham, Mohan; Sasidharan, P.; Kathuria, Shallu; Sharma, Cheshta; Meis, Jacques F.

    2014-01-01

    Cases of invasive mycosis due to Blastobotrys serpentis and B. proliferans identified by sequencing in a preterm patient and a rhabdomyosarcoma patient, respectively, are reported. Both species revealed elevated fluconazole and echinocandin MICs by the CLSI broth microdilution method. Additionally, B. serpentis exhibited high amphotericin B MICs, thus posing serious therapeutic challenges. PMID:25165080

  2. Allergic bronchopulmonary mycosis due to co-infection with Aspergillus fumigatus and Schizophyllum commune

    PubMed Central

    Seki, Masafumi; Ohno, Hideaki; Gotoh, Kazuyoshi; Motooka, Daisuke; Nakamura, Shota; Iida, Tetsuya; Miyazaki, Yoshitsugu; Tomono, Kazunori

    2014-01-01

    A 61-year-old female presented with eosinophilic pneumonia accompanied by bronchial asthma. She was finally diagnosed with allergic bronchopulmonary mycosis (ABPM) due to co-infection with Aspergillus fumigatus and Schizophyllum commune detected by genetic analysis of the plug and from cultures. PMID:26839766

  3. Allergic bronchopulmonary mycosis due to co-infection with Aspergillus fumigatus and Schizophyllum commune.

    PubMed

    Seki, Masafumi; Ohno, Hideaki; Gotoh, Kazuyoshi; Motooka, Daisuke; Nakamura, Shota; Iida, Tetsuya; Miyazaki, Yoshitsugu; Tomono, Kazunori

    2014-01-01

    A 61-year-old female presented with eosinophilic pneumonia accompanied by bronchial asthma. She was finally diagnosed with allergic bronchopulmonary mycosis (ABPM) due to co-infection with Aspergillus fumigatus and Schizophyllum commune detected by genetic analysis of the plug and from cultures.

  4. Epizootiological Modeling of Pandora neoaphidis Mycosis Transmission in Myzus persicae Colonies Initiated by Primarily Infected Alates

    PubMed Central

    Chen, Chun; Feng, Ming-Guang

    2005-01-01

    Pandora neoaphidis transmission was monitored within progeny colonies initiated by infected Myzus periscae alates individually flown for 1 to 5 h. Mycosis progress in the colonies was well fitted (r2 = 0.97) to a modified logistic or Gompertz model that included their flight distance, postflight survival time, premycosis fecundity, and primary infection rate as influential variables. PMID:16000827

  5. Epizootiological modeling of Pandora neoaphidis mycosis transmission in Myzus persicae colonies initiated by primarily infected alates.

    PubMed

    Chen, Chun; Feng, Ming-Guang

    2005-07-01

    Pandora neoaphidis transmission was monitored within progeny colonies initiated by infected Myzus periscae alates individually flown for 1 to 5 h. Mycosis progress in the colonies was well fitted (r2= 0.97) to a modified logistic or Gompertz model that included their flight distance, postflight survival time, premycosis fecundity, and primary infection rate as influential variables.

  6. General anesthesia for dental care management of a patient with epidermolysis bullosa: 24-month follow-up.

    PubMed

    Mello, Bianca Zeponi Fernandes; Neto, Natalino Lourenço; Kobayashi, Tatiana Yuriko; Mello, Marina Barbosa Almeida; Ambrosio, Eloá Cristina Passucci; Yaedú, Renato Yassutaka Faria; Machado, Maria Aparecida Andrade Moreira; Oliveira, Thais Marchini

    2016-07-01

    Epidermolysis bullosa comprises a group of uncommon skin-related diseases, characterized by the formation of blisters on mucocutaneous regions occurring spontaneously, following a trauma, exposure to heat, or as a result of minimal mechanical trauma. The dental treatment of the patient with epidermolysis bullosa raises many questions and discussions, due to the difficulty of carrying out the procedures. This report aimed to detail the clinical considerations of the treatment under general anesthesia of a patient with epidermolysis bullosa. The extraction of all deciduous teeth under general anesthesia was recommended based on the clinical and radiographic examinations. At 24-month follow-up, the patient had great improvement in oral hygiene without new caries lesions. The patient has been followed-up at every month for caries lesion prevention and permanent tooth development. The treatment under general anesthesia provided the ideal safe conditions and was beneficial for the patient. © 2016 Special Care Dentistry Association and Wiley Periodicals, Inc.

  7. Rat model for dominant dystrophic epidermolysis bullosa: glycine substitution reduces collagen VII stability and shows gene-dosage effect.

    PubMed

    Nyström, Alexander; Buttgereit, Jens; Bader, Michael; Shmidt, Tatiana; Ozcelik, Cemil; Hausser, Ingrid; Bruckner-Tuderman, Leena; Kern, Johannes S

    2013-01-01

    Dystrophic epidermolysis bullosa, a severely disabling hereditary skin fragility disorder, is caused by mutations in the gene coding for collagen VII, a specialized adhesion component of the dermal-epidermal junction zone. Both recessive and dominant forms are known; the latter account for about 40% of cases. Patients with dominant dystrophic epidermolysis bullosa exhibit a spectrum of symptoms ranging from mild localized to generalized skin manifestations. Individuals with the same mutation can display substantial phenotypic variance, emphasizing the role of modifying genes in this disorder. The etiology of dystrophic epidermolysis bullosa has been known for around two decades; however, important pathogenetic questions such as involvement of modifier genes remain unanswered and a causative therapy has yet to be developed. Much of the failure to make progress in these areas is due to the lack of suitable animal models that capture all aspects of this complex monogenetic disorder. Here, we report the first rat model of dominant dystrophic epidermolysis bullosa. Affected rats carry a spontaneous glycine to aspartic acid substitution, p.G1867D, within the main structural domain of collagen VII. This confers dominant-negative interference of protein folding and decreases the stability of mutant collagen VII molecules and their polymers, the anchoring fibrils. The phenotype comprises fragile and blister-prone skin, scarring and nail dystrophy. The model recapitulates all signs of the human disease with complete penetrance. Homozygous carriers of the mutation are more severely affected than heterozygous ones, demonstrating for the first time a gene-dosage effect of mutated alleles in dystrophic epidermolysis bullosa. This novel viable and workable animal model for dominant dystrophic epidermolysis bullosa will be valuable for addressing molecular disease mechanisms, effects of modifying genes, and development of novel molecular therapies for patients with dominantly

  8. Nasal Septal Deviation and Concha Bullosa – Do They Have an Impact on Maxillary Sinus Volumes and Prevalence of Maxillary Sinusitis?

    PubMed Central

    Kucybała, Iwona; Janik, Konrad Adam; Ciuk, Szymon; Storman, Dawid; Urbanik, Andrzej

    2017-01-01

    Summary Background The aim of the study was to assess if the presence of nasal septal deviation and concha bullosa is connected with the development of sinuses and the incidence of inflammation within them. Material/Methods We retrospectively analysed 214 patients who underwent paranasal sinus computed tomography. There were 125 females and 89 males, the mean age being 47.67±16.74 years (range 18–97). Exclusion criteria included: age under 18 years, prior sinonasal surgery and S-shaped septum. Results Mean volume of the right maxillary sinus was 17.794 cm3, while for the left one it was 17.713 cm3. Nasal septal deviation was found in 79.9% of computed tomography examinations and concha bullosa was observed in 42.1% of the patients’ examinations. There was an association between the presence of unilateral or dominant concha bullosa and contralateral direction of septal deviation [right-sided (p=0.039), left-sided (p=0.003)]. There was higher incidence of bilateral maxillary sinusitis in patients with septal deviation (p=0.007). Bilateral concha bullosa did not influence the incidence of bilateral maxillary sinusitis (p=0.495). Neither septal deviation (right sided: p=0.962; left-sided: p=0.731), nor unilateral/dominant concha bullosa (right: p=0.512; left: p=0,430) affected the asymmetry in volumes of maxillary sinuses. Bilateral concha bullosa was connected with larger volume of maxillary sinuses (right sinus: p=0.005; left sinus: p=0.048). Conclusions Nasal septal deviation, contrary to concha bullosa, has influence on the development of maxillary sinusitis. There is a connection between the presence of concha bullosa and direction of septal deviation. Only bilateral concha bullosa affects maxillary sinus volumes. PMID:28348652

  9. Balloon dilatation in esophageal strictures in epidermolysis bullosa and the role of anesthesia.

    PubMed

    Gollu, Gulnur; Ergun, Ergun; Ates, Ufuk; Can, Ozlem S; Dindar, Huseyin

    2017-02-01

    Esophageal involvement, which causes stricture, is a complication in epidermolysis bullosa. This causes dysphagia and malnutrition and leads to deterioration of skin lesions in these patients. The charts of 11 patients with epidermolysis bullosa and esophageal stricture who were included into dilatation program between 2003 and 2015 were retrospectively reviewed. Seven of the patients were female and four were male. The median age was 14 (2-32) years. The mean body weight of patients was 27.8 (9-51) kg. The location and number of strictured parts of the esophagus were previously evaluated with upper gastrointestinal contrast study and after that flexible endoscopy was used for dilatation. Eight patients had middle esophageal, three patients had proximal esophageal and one of them had both proximal and middle esophageal strictures. The strictures were dilated 56 times in total (mean 5 times). One patient underwent gastrostomy and was medically followed-up after a perforation occurrence during the dilatation procedure. In a 32-year-old female patient, colon interposition was performed after four dilatations since optimal nutritional and developmental status could not be achieved. The dilatation program of nine patients is still in progress. Seven of them can easily swallow solid food but two of them have some difficulties in swallowing between dilatations. One patient rejected the program and quitted, while one patient refused colon interposition and died because of complications related to amyloidosis during the dilatation program. After resolution of the swallowing problem, skin lesions were observed to heal quickly. Epidermolysis bullosa is a rare cause of dysphagia. Esophageal balloon dilatation with flexible endoscopy is a safe and efficient method in patients with this condition. © 2016 International Society for Diseases of the Esophagus.

  10. Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients.

    PubMed

    Woodley, David T; Cogan, Jon; Hou, Yingping; Lyu, Chao; Marinkovich, M Peter; Keene, Douglas; Chen, Mei

    2017-08-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease caused by mutations in the gene encoding type VII collagen, the major component of anchoring fibrils (AF). We previously demonstrated that gentamicin produced functional type VII collagen in RDEB cells harboring nonsense mutations. Herein, we determined whether topical or intradermal gentamicin administration induces type VII collagen and AFs in RDEB patients. A double-blind, placebo-controlled pilot trial assessed safety and efficacy of topical and intradermal gentamicin in 5 RDEB patients with nonsense mutations. The topical arm tested 0.1% gentamicin ointment or placebo application 3 times daily at 2 open erosion sites for 2 weeks. The intradermal arm tested daily intradermal injection of gentamicin solution (8 mg) or placebo into 2 intact skin sites for 2 days in 4 of 5 patients. Primary outcomes were induction of type VII collagen and AFs at the test sites and safety assessment. A secondary outcome assessed wound closure of topically treated erosions. Both topical and intradermal gentamicin administration induced type VII collagen and AFs at the dermal-epidermal junction of treatment sites. Newly created type VII collagen varied from 20% to 165% of that expressed in normal human skin and persisted for 3 months. Topical gentamicin corrected dermal-epidermal separation, improved wound closure, and reduced blister formation. There were no untoward side effects from gentamicin treatments. Type VII collagen induction did not generate anti-type VII collagen autoantibodies in patients' blood or skin. Topical and intradermal gentamicin suppresses nonsense mutations and induces type VII collagen and AFs in RDEB patients. Gentamicin therapy may provide a readily available treatment for RDEB patients with nonsense mutations. ClinicalTrials.gov NCT02698735. Epidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH, and VA Merit Award.

  11. Development and validation of an epidermolysis bullosa family/parental burden score.

    PubMed

    Dufresne, H; Hadj-Rabia, S; Taieb, C; Bodemer, C

    2015-12-01

    The notion of the individual burden associated with a disease has been introduced to determine 'disability' in the broadest sense: psychological, social, economic and physical. Subtypes of epidermolysis bullosa (EB) are rare, life-threatening, untreatable chronic genodermatoses. To develop and validate a specific questionnaire assessing the burden on families of children with EB: Epidermolysis Bullosa Burden of Disease (EB-BoD). Items were generated by a verbatim report from parents of children with EB. Subsequently, a study was implemented for psychometric analysis. An epidermolysis bullosa burden-of-disease questionnaire was refined via item reduction according to inter-question correlations, consensus among experts and exploratory factor analysis. Internal consistency was determined by calculating Cronbach's α. Concurrent validity was determined by calculating the correlation between EB-BoD and the Short-Form 12 items (SF-12) questionnaire. From a primary list of 30 items, EB-BoD was reduced to a 20-item questionnaire, covering four disease aspects based on the exploratory factor analysis. Construct validity was demonstrated and the EB-BoD questionnaire showed good internal consistency (Cronbach's α = 0·9). The resulting EB-BoD score was significantly correlated to the mental dimension of SF-12 (r = -0·61), but it was not correlated to it's physical dimension (r = 0·04). EB-BoD scores were significantly discriminating between EB subtypes. The EB-BoD questionnaire appears to be a useful assessment tool regarding medical and socioeconomic issues in patients with EB and their families. EB-BoD scores correlate well with the family/parental burden experienced by the families of patients with EB. © 2015 British Association of Dermatologists.

  12. Emergency Difficult Airway Management in a Patient with Severe Epidermolysis Bullosa

    PubMed Central

    Özkan, Ahmet Selim; Kayhan, Gülay Erdoğan; Akbaş, Sedat; Kaçmaz, Osman; Durmuş, Mahmut

    2016-01-01

    Epidermolysis bullosa (EB) is a rare disease characterised by vesiculobullous lesions with minimal trauma to the skin and mucous membranes. Bleeding, scar tissue, contractures, oedema and lesions that can spread throughout the body can cause a difficult airway and vascular access in patients with EB. Therefore, anaesthetic management in patients with EB is a major problem even for experienced anaesthesiologists. Herein, we report a case of difficult airway management in a patient diagnosed with severe EB who presented for emergency tracheostomy because of respiratory failure under general anaesthesia. PMID:27909609

  13. Junctional epidermolysis bullosa in two siblings: clinical observations, collagen studies and electron microscopy.

    PubMed

    Oakley, C A; Wilson, N; Ross, J A; Barnetson, R S

    1984-11-01

    Two siblings with junctional epidermolysis bullosa are described: both survived beyond parturition. They were treated with the usual therapeutic doses of phenytoin, dapsone, prednisolone, and zinc supplements without effect. Investigation of the skin of one of the patients showed that his fibroblasts, collagen synthesis and collagenase levels were normal. In view of the normality of the collagenase levels, it is probably not surprising that phenytoin was ineffective. Electron microscopy demonstrated junctional cleavage without pathology in the dermis itself: abnormal hemidesmosomes were seen as described previously, though it is suggested that this is not the primary abnormality which results in the disease process.

  14. Disseminated systemic mycosis in Veiled chameleons (Chamaeleo calyptratus) caused by Chamaeleomyces granulomatis.

    PubMed

    Schmidt, Volker; Plenz, Bastian; Pfaff, Miriam; Pees, Michael

    2012-12-28

    The aim of the examination was to gain knowledge on the incidence of Chamaeleomyces granulomatis mycosis in Veiled chameleons (Chamaeleo calyptratus), a disease which has recently been described as a single outbreak in a zoo collection. During a time period of 26 months (September 2009-November 2011) 18 Veiled chameleons presented at the clinic for various reasons were examined for the presence of C. granulomatis. Swabs were taken from tongue and skin lesions of live chameleons and from internal granulomas of deceased chameleons. Mycological culture was performed on Sabouraud dextrose and Potato dextrose agar as described previously. For the first time, the obtained isolates were screened for susceptibility towards different antifungal drugs by use of agar diffusion testing. Fungal species were determined by amplification with different primers, as reported before, and sequencing of parts of the 28S rDNA gene, the 18S rDNA gene, internal transcribed spacer region-1 DNA and 5.8S rDNA gene. Ten cases of disseminated mycosis caused by C. granulomatis were thus documented. These animals were kept in nine different collections of differing owners. Common findings in diseased chameleons were disseminated mycosis, glossitis and dermatitis. Although all isolates were tested sensitive to terbinafine and nystatin. The results of this study clearly show, contrary to a recently published single outbreak in a zoo collection, that disseminated mycosis caused by C. granulomatis in Veiled chameleons is, a common and often fatal infectious disease in this species. The routes of infection or treatment options are still unknown and need further investigation.

  15. Genotype, Clinical Course, and Therapeutic Decision Making in 76 Infants with Severe Generalized Junctional Epidermolysis Bullosa.

    PubMed

    Hammersen, Johanna; Has, Cristina; Naumann-Bartsch, Nora; Stachel, Daniel; Kiritsi, Dimitra; Söder, Stephan; Tardieu, Mathilde; Metzler, Markus; Bruckner-Tuderman, Leena; Schneider, Holm

    2016-11-01

    Severe generalized junctional epidermolysis bullosa, a lethal hereditary blistering disorder, is usually treated by palliative care. Allogeneic stem cell transplantation (SCT) has been proposed as a therapeutic approach, yet without clinical evidence. Decision making was evaluated retrospectively in 76 patients with severe generalized junctional epidermolysis bullosa born in the years 2000-2015. The diagnosis was based on the absence of laminin-332 in skin biopsies. With an incidence of 1 of 150,000, severe generalized junctional epidermolysis bullosa occurred more often than published previously. Eleven as yet unreported mutations in the laminin-332 genes were detected. Although patients homozygous for the LAMB3 mutation c.1903C>T lived longer than the others, life expectancy was greatly diminished (10.8 vs. 4.6 months). Most patients failed to thrive. In two patients with initially normal weight gain, the decision for SCT from haploidentical bone marrow or peripheral blood was made. Despite transiently increasing skin erosions, the clinical status of both subjects stabilized for several weeks after SCT, but finally deteriorated. Graft cells, but no laminin-332, were detected in skin biopsies. The patients died 96 and 129 days after SCT, respectively, one of them after receiving additional skin grafts. Treatment of severe generalized junctional epidermolysis bullosa by SCT is a last-ditch attempt still lacking proof of efficacy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. End-stage kidney disease in patient with epidermolysis bullosa - what are the treatment options? - case report.

    PubMed

    Małecki, Michał; Domański, Maciej; Ciechanowski, Kazimierz

    2017-06-14

    Epidermolysis bullosa is a group of diseases caused by mutations in genes for proteins responsible for cells' anchorage at the dermo-epidermal junction. Their common feature are dysfunctional or even absent connections between cells. The typical clinical sign is the formation of blisters, with possible excessive scarring, in response to minimal skin irritation. End stage renal disease may be one of the comorbidities in patients with epidermolysis bullosa. The implementation of renal replacement therapy may be very difficult in this population. This is mainly due to problems in obtaining the proper dialysis access. The choice of appropriate method may be crucial for patient's survival. We present a case of 29-year-old woman with Epidermolysis bullosa caused by laminin 5 gene mutation. The patient suffered from additional conditions: blindness, complete bilateral sensorineural deafness and oesophageal stenosis. When end stage renal disease was diagnosed, the problem of renal replacement therapy had to be faced. There have been few reports concerning ESRD in this specific group of patients in the available literature. In most of them the prognosis was very poor. Nevertheless, we were very determined to overcome all the difficulties. Special procedures and cooperation with the patient's family allowed us to consider kidney transplantation as a treatment option. There should be no limitations in renal replacement therapy in patients with epidermolysis bullosa. Haemodialysis, peritoneal dialysis and kidney transplantation are all possible treatment options. Nevertheless, either method requires special procedures.

  17. Congenital dystrophic epidermolysis bullosa (DEB) in Sprague Dawley rats: a case series.

    PubMed

    Eden, Kristin B; Peterson, Ashley; Payne, Harold R; Corapi, Wayne V; Mansell, Joanne; Hoffman, Aline Rodrigues

    2016-04-01

    Epidermolysis bullosa is a rare skin disease caused by defects in the basement membrane and/or other dermoepidermal junction components. We describe a series of spontaneous cases of dystrophic epidermolysis bullosa (DEB) in a colony of Sprague Dawley rats investigated with histopathology, transmission electron microscopy (TEM) and inheritance pattern. Four, 4-day-old pups from a litter of Sprague Dawley rats developed blistering, haemorrhagic skin lesions and were euthanized. Age-matched controls from the same litter were normal. Several months later two more litters presented with identical findings. All three litters had the same sire, suggesting a genetic component. Skin from affected and control animals was evaluated histologically and with TEM. Unaffected sibling pairs from affected litters were bred in order to potentially reproduce the disease and determine the mode of inheritance. Histologically, there was significant dermoepidermal clefting below the basement membrane with variable amounts of haemorrhage and cellular debris within the clefts. Ultrastructurally, clefting occurred below the basement membrane with an intact lamina densa and normal hemidesmosomes. Anchoring filaments were strikingly absent. Litters produced from phenotypically unaffected sibling pairs resulted in a total of four more litters with approximately a quarter of pups affected. Based on the gross lesions, histopathological features and TEM determination of separation below the lamina densa and lack of normal anchoring fibrils, these cases are most consistent with DEB. This is the first report of naturally occurring, localized and reproducible recessive DEB in Sprague Dawley rats. © 2016 ESVD and ACVD.

  18. Raising Awareness Among Healthcare Providers about Epidermolysis Bullosa and Advancing Toward a Cure

    PubMed Central

    Tabor, Aaron; Pergolizzi, Joseph V.; Marti, Guy; Harmon, John; Cohen, Bernard

    2017-01-01

    Objective: Epidermolysis bullosa (EB) is an orphan disease that affects about half a million people worldwide, but may not be familiar to all clinicians. The authors’ goal was to present a short description of this condition and current research in the form of a narrative review. Methods: The authors reviewed the literature on epidermolysis bullosa in order to describe the condition and current genetic research. Results: There are at least 31 subtypes of EB, including junctional EB, dystrophic EB, and Kindler syndrome. Genetic research is crucial in finding strategies to manage and possibly cure EB, which is often undiagnosed or misdiagnosed. EB may present in newborns and may persist over the course of a lifetime. Serious complications can occur with EB, including chronic blisters, wounds, ulcers, pruritus, clubbing of hands and feet, and amputations. Pain is frequently reported. About 80 percent of patients with recessive dystrophic EB will succumb to squamous cell carcinoma by age 55. Promising directions for future research include genome editing, gene therapy, and cell-based therapies. Conclusion: Our growing understanding of genetics and cell therapies may lead to promising therapeutic advances to treat this challenging condition. PMID:28670357

  19. Type VII Collagen Replacement Therapy in Recessive Dystrophic Epidermolysis Bullosa-How Much, How Often?

    PubMed

    South, Andrew P; Uitto, Jouni

    2016-06-01

    Recessive dystrophic epidermolysis bullosa is a devastating blistering disease caused by mutations in the COL7A1 gene, which encodes type VII collagen, the major component of anchoring fibrils. The anchoring fibrils in patients with recessive dystrophic epidermolysis bullosa can be morphologically altered, reduced in number, or absent entirely. There is no specific treatment for this disease, but recent advances in gene, protein replacement, or cell-based therapies, with the purpose of delivering functional type VII collagen to the skin, have shown encouraging results in both preclinical and clinical settings. One critical issue is the stability of type VII collagen in anchoring fibrils, which will ultimately determine the dose and frequency of administration of the missing protein. Kühl et al. attempted to determine the half-life of type VII collagen in the skin, tongue, and esophagus of genetically altered mice that express type VII collagen constitutively, but with its expression abrogated by genetic manipulation. Their results revealed a half-life much shorter than previously anticipated, some 30 days. These findings have implications for strategies to be used for protein replacement therapy, and they also suggest that the basement membrane components at the dermal-epidermal junction are subject to ongoing remodeling and turnover. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Access to wound dressings for patients living with epidermolysis bullosa - an Australian perspective.

    PubMed

    Stevens, Louise J

    2014-10-01

    Epidermolysis Bullosa (EB) is a rare genetic skin disorder characterised by fragility and blistering of skin and mucous membranes. Skin can blister and shear away from minimal friction, trauma and every day activities. The disease causes a wide range of complications but wound care is the major challenge to severe EB, and good wound care is an essential part of wound management. The goal of wound care was to choose a product that protects the fragile skin, limits friction, decreases pain and promotes healing. However, access to wound dressings for those people living with EB is challenging. This article discusses the availability of EB dressings in a number of countries around the world and also describes an innovative National Epidermolysis Bullosa Dressings Scheme (NEBDS) in Australia, which aims to improve the quality of life of people with EB, by reducing the financial burden associated with the provision of dressings accordingly. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  1. Generalized severe junctional epidermolysis bullosa with congenital absence of skin in churra lambs.

    PubMed

    Benavides, Julio; Suárez-Vega, Aroa; Gutiérrez, Jorge; de la Hera, Sandra; Fuertes, Miguel; Delgado, Laetitia; Fernández, Miguel; Ferreras, María del Carmen; Arranz, Juan José; Pérez, Valentín

    2015-10-01

    Up to 0.5% of churra lambs from two genetically related flocks showed congenital skin lesions of variable severity, jeopardizing the life of the lambs in the most severe cases. The primary objective of this study was to classify the type of congenital epithelial disease suffered by these animals, based on the description of the macroscopic skin defects, the histological and ultrastructural changes and the hereditary nature of the condition. Thirty affected newborn lambs from two genetically related flocks were studied. Three additional lambs acquired from two other flocks, which had no grossly apparent skin lesions and had died of infectious diseases, were studied as unaffected control animals. Histological and ultrastructural examinations of skin and oral mucosa samples were performed. Pedigree analyses were used to investigate genealogical relationships. Generalized severe junctional epidermolysis bullosa with congenital absence of skin was described in all lambs studied and an autosomal recessive mode of inheritance was identified. The pathological findings and mode of inheritance in these lambs are similar to an inherited epidermolysis bullosa subtype of humans, which has not been reported previously in veterinary medicine. © 2015 ESVD and ACVD.

  2. A Mouse Model of Generalized non-Herlitz Junctional Epidermolysis Bullosa

    PubMed Central

    Bubier, Jason A.; Sproule, Thomas J.; Petell, Lydia; Webb, Cameron; Fine, Jo-David; Roopenian, Derry C.; Sundberg, John P.

    2010-01-01

    Epidermolysis bullosa (EB) is a class of intractable, rare, genetic disorders characterized by fragile skin and blister formation as a result of dermal-epidermal mechanical instability. EB presents with considerable clinical and molecular heterogeneity. Viable animal models of junctional epidermolysis bullosa (JEB), that both mimic the human disease and survive beyond the neonatal period, are needed. We identified a spontaneous, autosomal recessive mutation (Lamc2 jeb) due to a Murine Leukemia Virus long terminal repeat insertion in Lamc2 that results in a hypomorphic allele with reduced levels of LAMC2 protein. These mutant mice develop a progressive blistering disease validated at the gross and microscopic levels to closely resemble generalized non-Herlitz JEB. The Lamc2 jeb mice display additional extracutaneous features such as loss of bone mineralization and abnormal teeth, as well as a respiratory phenotype that is recognized but not as well characterized in humans. This model faithfully recapitulates human JEB and provides an important preclinical tool to test novel therapeutic approaches. PMID:20336083

  3. Chronic leg ulcers as a rare cause for the first diagnosis of epidermolysis bullosa dystrophica.

    PubMed

    Bafaraj, Mazin G; Cesko, Elvir; Weindorf, Maren; Dissemond, Joachim

    2014-06-01

    Chronic leg ulcers occur most frequently in the elderly population as a result of an underlying vascular disease especially chronic venous insufficiency. But it also occurs less commonly in younger people due to other aetiologies, for example, infections, vasculitis, neoplasia or genetic diseases. The following case report presents chronic leg ulcers as a rare cause for the first diagnosis of dystrophic epidermolysis bullosa. We report about a 21-year-old man with painful chronic leg ulcers resistant to different wound treatments for 4 months. After exclusion of the more common vascular aetiologies and reviewing the patient's family history, we considered an epidermolysis bullosa dystrophica which could be confirmed by genetic analyses. We treated the patient with debridement, modified negative pressure therapy with non-adhesive foil and skin grafting. The chronic leg ulcers healed completely. This case report demonstrates that the family history and genetic diseases should be considered as rare causes for therapy-refractory chronic leg ulcers, especially in young patients. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  4. Clinical features of gingival lesions in patients with dystrophic epidermolysis bullosa: a cross-sectional study.

    PubMed

    Fortuna, G; Aria, M; Cepeda-Valdes, R; Pollio, A; Moreno-Trevino, M G; Salas-Alanís, J C

    2015-03-01

    Gingival lesions in patients with dystrophic epidermolysis bullosa (DEB) are a common manifestation. However, their clinical features, frequency and severity are currently unknown. Forty-five DEB patients were assessed by an oral medicine specialist, who analysed the presence/absence of four clinical signs (erythema, erosion/ulcer, atrophy, blister) on free and attached gingiva, using the Epidermolysis Bullosa Oropharyngeal Severity score. Twenty-eight (62.2%) out of 45 DEB patients showed different types of gingival lesions, whose presence/absence and total frequency/distribution were not significantly different between males and females (p=0.087 and p=0.091, respectively). Erythema was the most prevalent lesion (66.2%) and the recessive DEB severe generalized (RDEB-sev gen) reached the highest median disease activity score. A significant correlation was observed between the DEB subtypes and the disease activity median score (p<0.001), but not between age and total disease activity score in each group of DEB (p>0.05). Lastly, logistic regression showed that only gender (p=0.031) and RDEB-sev gen (p=0.001) were risks factors for the presence of gingival lesions. Gingival lesions in DEB patients are a relatively common entity and may have multiple clinical aspects, emphasizing the need for thorough attention and awareness among dentists. © 2015 Australian Dental Association.

  5. Mutational founder effect in recessive dystrophic epidermolysis bullosa families from Southern Tunisia.

    PubMed

    Ben Brick, Ahlem Sabrine; Laroussi, Nadia; Mesrati, Hela; Kefi, Rym; Bchetnia, Mbarka; Lasram, Khaled; Ben Halim, Nizar; Romdhane, Lilia; Ouragini, Houyem; Marrakchi, Salaheddine; Boubaker, Mohamed Samir; Meddeb Cherif, Mounira; Castiglia, Daniele; Hovnanian, Alain; Abdelhak, Sonia; Turki, Hamida

    2014-05-01

    Dystrophic epidermolysis bullosa (DEB) is a group of heritable bullous skin disorders caused by mutations in the COL7A1 gene. One of the most severe forms of DEB is the severe generalized [recessive dystrophic epidermolysis bullosa (RDEB-SG)] subtype, which is inherited in an autosomal recessive manner. This subtype is most often due to COL7A1 mutations resulting in a premature termination codon on both alleles. We report here, the molecular investigation of 15 patients belonging to 14 nuclear families from the city of Sfax in Southern Tunisia, with clinical features of RDEB-SG complicated by squamous cell carcinoma in 3 patients. We identified two novel mutations, p.Val769LeufsX1 and p.Ala2297SerfsX91, in addition to one previously reported mutation (p.Arg2063Trp). The p.Val769LeufsX1 mutation was shared by 11 families and haplotype analysis indicated that it is a founder mutation. The p.Ala2297SerfsX91 mutation was a private mutation found in only one family. Together with the previously described recurrent mutations in Tunisia, screening for the founder p.Val769LeufsX1 mutation should provide a rapid molecular diagnosis tool for mutation screening in RDEB patients from Southern Tunisia and possibly from other Mediterranean populations sharing the same genetic background.

  6. Genotype-oropharyngeal phenotype correlation in Mexican patients with dystrophic epidermolysis bullosa.

    PubMed

    Fortuna, G; Pollio, A; Aria, M; Moreno-Trevino, M G; Marasca, F; Salas-Alanís, J C

    2014-04-01

    Previous investigations have attempted to correlate the genotype with the cutaneous phenotype in patients with epidermolysis bullosa (EB), but never with the oropharyngeal phenotype. Seventeen dystrophic EB (DEB) patients were genotyped for COL7A1 gene mutations and divided into five distinct groups. Oropharyngeal disease severity was assessed with the Epidermolysis Bullosa Oropharyngeal Severity (EBOS) score by an oral medicine specialist. The genotype-phenotype correlation was calculated by Kruskal-Wallis analysis of variance using the Mann-Whitney test, applying the Bonferroni correction. The most severe oropharyngeal phenotype was found in the group with the 2470insG/3948insT mutation, with a mean disease severity score of 18.50 ± 2.12; the mildest was found in the 6862del16 mutation group, with a mean disease severity score of 0.57 ± 1.13. The most significant difference in median score was found in the total score (P = 0.009), followed by tongue (P = 0.02) and upper lip (P = 0.021), but no correlation was found between disease severity and the groups (P>0.005, after Bonferroni correction). Multiple comparisons among the five different genotypic groups revealed no statistically significant genotype-oropharyngeal phenotype correlation; it was not possible to establish which group was more severe, or to associate a specific mutation to a specific oropharyngeal phenotype.

  7. Korean Monozygotic Twins with Lethal Acantholytic Epidermolysis Bullosa Caused by Two Novel DSP Mutations.

    PubMed

    Kim, Se Jin; Ko, Jung Min; Shin, Seung Han; Kim, Ee-Kyung; Kim, Han-Suk; Lee, Kyung-A

    2017-03-01

    Desmoplakin is an essential cytoplasmic plaque protein in desmosomes, and it is the major linker between intercellular junctions in the skin and heart. The role of desmoplakin is anchoring transmembrane cadherins to cytoplasmic intermediate filaments. The desmoplakin gene (DSP) is located on chromosome 6, and six common allelic disorders are associated with this gene, including autosomal-dominant or -recessive disorders that affect the skin, heart, hair, and nails. In particular, lethal acantholytic epidermolysis bullosa (LAEB) is an autosomal recessively inherited and extremely rare genetic skin disorder, and only three molecularly confirmed families with LAEB have been reported previously. Generalized oozing erosion of the entire skin is the main clinical feature, which leads to excessive transcutaneous fluid loss and neonatal death. Histopathologically, this disorder is classified as a suprabasal subtype of epidermolysis bullosa simplex. In this study, we report for the first time in Korea on monozygotic twins with LAEB caused by two novel nonsense mutations in the DSP gene. Both of the twins exhibited severe and rapid progressive whole body skin erosion, and they died shortly after birth because of multiorgan failure followed by excessive fluid loss. © 2017 by the Association of Clinical Scientists, Inc.

  8. Full-arch fixed prosthesis supported by four implants in patients with recessive dystrophic epidermolysis bullosa.

    PubMed

    Peñarrocha-Oltra, David; Peñarrocha-Diago, María; Balaguer-Martínez, Jose; Ata-Ali, Javier; Peñarrocha-Diago, Miguel

    2011-08-01

    The aim of this study was to describe the rehabilitation of patients diagnosed with recessive dystrophic epidermolysis bullosa (RDEB), with edentulous maxillas and/or mandibles, by using fixed full-arch short-expand prostheses supported by 4 anterior implants. A retrospective study was carried out to study edentulous patients with RDEB rehabilitated with fixed full-arch prostheses supported by 4 anterior implants. In total, 32 anterior implants were placed and used to support 8 full-arch fixed prostheses; 20 implants were placed in the maxilla by using osteotomes and 12 in the mandible by using conventional drilling. Implant success rate was 100% after an average follow-up of 22.9 (range 12-48) months after prosthetic loading. Patient satisfaction with the implant therapy was very high (mean 9.0) for all the factors assessed. Fixed full-arch short-expand prostheses supported by 4 anterior implants can be successfully used to rehabilitate patients with recessive dystrophic epidermolysis bullosa, considerably improving these patients' quality of life. Copyright © 2011 Mosby, Inc. All rights reserved.

  9. [Successful treatment of Norwegian scabies with ivermectin in a patient with recessive dystrophic epidermolysis bullosa].

    PubMed

    Angelo, C; Pedicelli, C; Provini, A; Annessi, G; Zambruno, G; Paradisi, M

    2004-06-01

    A 14 year-old female born from consanguineous healthy parents was admitted to our institute for the presence of a generalized bullous eruption started at birth. The bullae were asymmetrically distributed all over the cutaneous surface and, over time, evolved into erosions that resolved with scarring areas. On the basis of the clinical picture and the ultrastructural and antigenic studies, a diagnosis of recessive dystrophic epidermolysis bullosa was made. In the following months, the patient began to complain a severe pruritus and the bullae and erosions were accompanied with diffuse erythematous patches and plaques covered by thick scale-crusts situated mostly on the arms. Microscopic examination of the scales revealed the presence of many mites and ova. Since the conventional topical therapies for scabies were uneffective, the patient was treated with a single dose (200 mcg/hg) of ivermectin. Although there was an initial improvement, scabies recurred within 2 months from discontinuation of the therapy. Finally, a further single administration of ivermectin at the same dosage led to the complete and permanent resolution of scabies. The association of recessive dystrophic epidermolysis bullosa and norwegian scabies has been already reported in literature. The case presented suggests that ivermectin represents an effective drug for severe forms of scabies occurring in patients affected by other dermatoses that prevent the use of topical treatments.

  10. Dystrophic epidermolysis bullosa with one dominant and one recessive mutation of the COL7A1 gene in a child with deafness.

    PubMed

    Weinel, Sarah; Lucky, Anne W; Uitto, Jouni; Pfendner, Ellen G; Choo, Daniel

    2008-01-01

    Dystrophic epidermolysis bullosa can be inherited in autosomal dominant and recessive forms, the former usually expressed as a milder phenotype, although mild forms of recessive dystrophic epidermolysis bullosa can occur. We present a patient who was found to be a compound heterozygote, inheriting a dominant mutation from his father and a recessive mutation from his mother, resulting in a clinically severe case of dystrophic epidermolysis bullosa. Mutations in the gene for collagen VII (COL7A1) have been documented in both types of dystrophic epidermolysis bullosa. Our patient has also been diagnosed with bilateral auditory neuropathy, a disorder coincidentally also mapped to a nearby gene on chromosome 3p21 (the transmembrane inner ear expressed gene, TMIE).

  11. Proinflammatory Cytokines and Antiskin Autoantibodies in Patients With Inherited Epidermolysis Bullosa.

    PubMed

    Annicchiarico, Giuseppina; Morgese, Maria Grazia; Esposito, Susanna; Lopalco, Giuseppe; Lattarulo, Michele; Tampoia, Marilina; Bonamonte, Domenico; Brunetti, Luigia; Vitale, Antonio; Lapadula, Giovanni; Cantarini, Luca; Iannone, Florenzo

    2015-10-01

    Epidermolysis bullosa (EB) is a rare disorder characterized by inherited skin adhesion defects with abnormal disruption of the epidermal-dermal junction in response to mechanical trauma. Our aim was to investigate a set of cytokine levels in serum samples from patients suffering from epidermolysis bullosa simplex (EBS), dystrophic epidermolysis bullosa (DEB), and healthy controls (HCs), exploring their potential correlations with antiskin autoantibody titers and disease activity. Forty patients afferent to the Dermatological Ward of Bari City Hospital and 9 HCs were enrolled and subdivided according to the dystrophic (DEB) and simplex forms (EBS). We found a significant increase in interleukin (IL)-1β plasmatic levels of DEB (P = 0.0224) and EBS (P = 0.0465) patients compared to HCs; IL-6 levels were significantly higher in DEB than in EBS patients (P = 0.0004) or HCs (P = 0.0474); IL-2 levels were significantly increased in DEB compared with EBS (P = 0.0428). Plasmatic tumor necrosis factor-β and interferon-γ were higher in DEB patients than in HCs (P = 0.0448 and 0.0229). Conversely, tumor necrosis factor-α was significantly decreased in DEB (P = 0.0034). IL-5 correlated with anti-BP180 (r = -0.5018, P = 0.0338), anti-BP230 (r = -0.6097, P = 0.0122), and anticollagen VII (r = -0.5166, P = 0.0405) autoantibodies; interferon-γ correlated with anti-BP180 (r = 0.9633, P < 0.0001), anti-BP230 (r = 0.9071, P < 0.0001), and anticollagen VII (r = 0.8619, P = 0.0045) autoantibodies. Score of disease severity was significantly correlated with IL-6 (r = 0.6941, P = 0.029) and IL-12 (r = 0.5503, P = 0.0272). The present study supports that EB might be considered a systemic inflammatory disease rather than a skin-limited disorder; clinical disease activity scores could be also integrated by laboratory data such as IL-6 and IL-12 dosage; biotherapies targeting specific cytokine networks probably represent a way to go in the future.

  12. Improved polymerase chain reaction-based method to detect early-stage epitheliotropic T-cell lymphoma (mycosis fungoides) in formalin-fixed, paraffin-embedded skin biopsy specimens of the dog.

    PubMed

    Chaubert, Pascal; Baur Chaubert, Audrey S; Sattler, Ursula; Forster, Ursula; Bornand, Valérie; Suter, Maja; Welle, Monika

    2010-01-01

    In the dog, early-stage epitheliotropic T-cell lymphoma (ETCL) can clinically and histologically mimic a large range of inflammatory dermatoses and often progresses rapidly to a more aggressive tumor stage. Early diagnosis of ETCL is essential to proceed with a specific oncologic therapy that is favorable for the prognosis. In the present study, an improved method for the detection of T-cell receptor gamma (TCRgamma) rearrangement was developed by designing a new set of consensus primers to amplify the different forms of rearranged canine TCRgamma gene sequences by polymerase chain reaction. The amplicons were analyzed by conventional polyacrylamide gel electrophoresis, which requires minimal specific equipment and may be performed in almost every pathology laboratory at low costs. The method proved to be highly specific and sensitive to detect early ETCL in formalin-fixed, paraffin-embedded biopsy specimens, providing an efficient tool for veterinary pathologists to distinguish early neoplastic from reactive cutaneous T-cell infiltrates (tumor-specific marker) or to discriminate T-cell lymphoma from B-cell lymphomas or nonlymphoid neoplasms (T-cell lineage marker). By direct sequencing analysis of amplified TCRgamma gene sequences, ETCL was found to rearrange exclusively the joining (J) 4 region, which suggests specific biology for primary cutaneous T-cell lymphomas. Also, a novel (seventh) functional J region in the TCRgamma gene, localized approximately 2.3 kb upstream of J5, was identified.

  13. The incidence of concha bullosa, unusual anatomic variation and its relationship to nasal septal deviation: A retrospective radiologic study.

    PubMed

    Koo, Soo Kweon; Kim, Jong Deok; Moon, Ji Seung; Jung, Sung Hoon; Lee, Sang Hoon

    2017-10-01

    Identifying anatomical variations associated with pathological findings is very useful for diagnoses and therapeutics. We conducted a study to detect various anatomical variations (superior, middle, inferior turbinate concha bullosa, uncinate bulla and nasal swell body [NSB]) in connection with nasal septal deviation. This study used a retrospective radiological design to analyze 594 (1188 sides) osteomeatal computed tomography scans from 494 male patients and 100 female patients aged between 17 and 75 years. We randomly selected 100 male and 100 female patients as controls; we compared the groups and performed a statistical analysis. All patients in the control group had sinusitis only (i.e., they lacked nasal septal deviations). Left-sided septal deviation was found to be slightly more prevalent than right-sided deviation (43.9% and 36.4%, respectively). The incidence of S-curved septal deviation was 18.5%, that of dorso-ventral deviation was 10.9%, and that of caudal-rostral deviation was 7.6%. The incidence of only septal spur was 1.2%. In the case of middle turbinate concha bullosa, the incidence of the unilateral type was 17.3% and that of the bilateral type was 36.4%. In superior turbinate concha bullosa, the incidence of the unilateral type was 11.3% and that of the bilateral type was 27.4%. The incidence of inferior turbinate concha bullosa was 1.0% and that of uncinate bulla was 1.7%. NSB was found in 25.1% of patients, 24.7% of males and 27.0% of females. The frequencies of middle and superior concha bullosa were about 10-12 fold higher on the concave side. The nasal septal deviation group exhibited a higher incidence of most anatomical variants than the non-deviated group; differences in the middle turbinate concha bullosa attained statistical significance. The radiologist must focus on anatomical variants in the preoperative evaluation. It is important for surgeons to be aware of these variations. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. A case of sinobronchial allergic mycosis; possibility of basidiomycetous fungi as a causative antigen.

    PubMed

    Ogawa, Haruhiko; Fujimura, Masaki; Takeuchi, Yasuo; Makimura, Koichi

    2011-01-01

    We herein report a case of sinobronchial allergic mycosis (SAM) caused by basidiomycetous (BM) fungi (probably Phanerochaete velutina). The patient with bronchial asthma that accompanied allergic fungal sinusitis (AFS) fulfilled all 6 criteria for diagnosing SAM. In this case, the BM fungus may act as an allergen, reacting continually in both the upper and lower respiratory tract. The antifungal drug (itraconazole 50 mg/day) seemed to achieve a partial response. Basidiomycetous fungi may attract attention because of the possibility as a causative antigen in this new clinical concept of SAM.

  15. Primary cutaneous mucormycosis presenting as a giant plaque: uncommon presentation of a rare mycosis.

    PubMed

    Vinay, Keshavamurthy; Chandrasegaran, Ariganesh; Kanwar, Amrinder J; Saikia, Uma N; Kaur, Harsimran; Shivaprakash, M R; Dogra, Sunil

    2014-08-01

    Mucormycosis is an uncommon systemic mycosis affecting the immunocompromised individuals. It is usually caused by organisms of the genera Rhizopus and Mucor, although rarely other organisms have also been implicated. Mycoses due to these angioinvasive fungi have an acute onset, rapidly progressive course with high mortality rate. A rare and less well known is the chronic subtype of primary cutaneous mucormycosis (PCM). Herein, we report a case of PCM clinically presenting as a chronic, giant destructive plaque in a young immunocompetent male and coin the term chronic granulomatous mucormycosis. A clinicopathological classification for cutaneous mucormycosis is also proposed.

  16. [Epidermolysis bullosa acquisita complicated by esophageal stenosis. Endoscopic treatment with thermoplastic dilators and intralesional steroid injection].

    PubMed

    Moura, E G; Couto-Júnior, D S; Alvarado-Escobar, H; da Costa-Martins, B; Sallum, R A; Artifon, E L; Sakai, P

    2011-01-01

    Epidermolysis bullosa acquisita (EBA) is a rare auto-immune dermatologic disease, produced by auto-antibodies against colagen VII. We report a 44 years old male patient with EBA diagnosed 15 years before, who presented with progressive disphagia, being diagnosed an esophageal involvement of EBA. The patient was submitted to endoscopic treatment with thermoplastic bougie dilation and intralesional corticosteroid injection. The patient improved clinically with recovery of nutritional status. Esophageal involvement in EBA is very rare and its reason is still unknown. Endoscopic approach must be cautiously performed with the use of small diameter endoscopes, small caliber dilators, intralesional injection of corticosteroid and enteral tube in order to minimize the risks of complications, as well as esophageal rest from food trauma and better reparatory molding of the epithelium.

  17. Treatment decision-making for patients with the Herlitz subtype of junctional epidermolysis bullosa.

    PubMed

    Yan, E G; Paris, J J; Ahluwalia, J; Lane, A T; Bruckner, A L

    2007-05-01

    The Herlitz subtype of junctional epidermolysis bullosa (JEB-H) is a lethal genetic disorder characterized by recurrent and persistent erosions of the epithelial surfaces that heal with exuberant granulation tissue. In addition, respiratory distress, refractory anemia and failure to thrive are often seen. Mortality in the first year of life approaches 90%. JEB-H is caused by mutations in the genes that encode the protein laminin 5, a structural molecule involved in the adhesion of epidermis to dermis. There is currently no cure for JEB-H. Medical interventions treat complications but do not ultimately limit mortality. Ethical principles contend that offering comfort and company to the patient and family, not aggressive therapies, should comprise the mainstay of care for affected infants.

  18. Polymeric Nanoparticles to Combat Squamous Cell Carcinomas in Patients with Dystrophic Epidermolysis Bullosa

    PubMed Central

    Rajadas, Jayakumar; Inayathullah, Mohammed

    2014-01-01

    Skin cancer is the leading cause of malignancy in the United States, with Basal Cell Carcinoma, Squamous Cell Carcinoma , and Melanoma being the three most common diagnoses, respectively. Squamous Cell Carcinoma (SCC) is a particular concern for patients suffering from Dystrophic Epidermolysis Bullosa (DEB), a disease that affects the production and function of collagen VII, a protein that forms the anchoring fibrils which bind the epidermis to the dermis. Patients with DEB suffer from chronic blistering and wounds that have impaired healing capabilities, often leading to the development of SCC and eventual mortality. Nanomedicine is playing an increasing role in the delivery of effective therapeutics to combat a wide range of diseases, including the imaging and treatment of SCC. In this review, we discuss the role of nanoparticles in the treatment of SCC with an emphasis on PLGA nanoparticles and SCCs found in patients suffering from DEB, and address recent patents that are pertinent to the development of novel nanomedical therapeutics. PMID:25506404

  19. Cytoskeletal Regulation of Inflammation and Its Impact on Skin Blistering Disease Epidermolysis Bullosa Acquisita

    PubMed Central

    Kopecki, Zlatko; Ludwig, Ralf J.; Cowin, Allison J.

    2016-01-01

    Actin remodelling proteins regulate cytoskeletal cell responses and are important in both innate and adaptive immunity. These responses play a major role in providing a fine balance in a cascade of biological events that results in either protective acute inflammation or chronic inflammation that leads to a host of diseases including autoimmune inflammation mediated epidermolysis bullosa acquisita (EBA). This review describes the role of the actin cytoskeleton and in particular the actin remodelling protein called Flightless I (Flii) in regulating cellular inflammatory responses and its subsequent effect on the autoimmune skin blistering disease EBA. It also outlines the potential of an antibody based therapy for decreasing Flii expression in vivo to ameliorate the symptoms associated with EBA. PMID:27420054

  20. Newborn with severe epidermolysis bullosa: to treat or not to treat?

    PubMed

    Boesen, Martin Lehmann; Bygum, Anette; Hertz, Jens Michael; Zachariassen, Gitte

    2016-04-26

    Epidermolysis bullosa (EB) is an inherited skin disease with four main subtypes that cannot be distinguished clinically at birth. All subtypes may present with widespread life-threatening blisters and fragile skin, making treatment and handling of the newborn with EB challenging. The prognosis of EB depends on the subtype, and therefore maximum treatment is necessary until the final diagnosis is known. In this case, it took 2 weeks before a final diagnosis was reached. In the meantime, we had several ethical discussions on the treatment level. The most important issues were management of pain and nutrition. For immediate pain relief, intranasal fentanyl worked best and gabapentin was successfully used for chronic pain. The feeding difficulties were handled first by a nasogastric feeding tube. Later a normal feeding bottle proved to be adequate. 2016 BMJ Publishing Group Ltd.

  1. From Marrow to Matrix: Novel Gene and Cell Therapies for Epidermolysis Bullosa

    PubMed Central

    Webber, Beau R; Tolar, Jakub

    2015-01-01

    Epidermolysis bullosa encompasses a group of inherited connective tissue disorders that range from mild to lethal. There is no cure, and current treatment is limited to palliative care that is largely ineffective in treating the systemic, life-threatening pathology associated with the most severe forms of the disease. Although allogeneic cell- and protein-based therapies have shown promise, both novel and combinatorial approaches will undoubtedly be required to totally alleviate the disorder. Progress in the development of next-generation therapies that synergize targeted gene-correction and induced pluripotent stem cell technologies offers exciting prospects for personalized, off-the-shelf treatment options that could avoid many of the limitations associated with current allogeneic cell-based therapies. Although no single therapeutic avenue has achieved complete success, each has substantially increased our collective understanding of the complex biology underlying the disease, both providing mechanistic insights and uncovering new hurdles that must be overcome. PMID:25803200

  2. Gene editing toward the use of autologous therapies in recessive dystrophic epidermolysis bullosa

    PubMed Central

    Perdoni, Christopher; Osborn, Mark J.; Tolar, Jakub

    2015-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is a disease caused by mutations in the COL7A1 gene that result in absent or dysfunctional type VII collagen protein production. Clinically, RDEB manifests as early and severe chronic cutaneous blistering, damage to internal epithelium, an elevated risk for squamous cell carcinoma and an overall reduced life expectancy. Recent localized and systemic treatments have shown promise for lessening the disease severity in RDEB, but the concept of ex vivo therapy would allow a patient’s own cells to be engineered to express functional type VII collagen. Here we review gene delivery and editing platforms, and their application toward the development of nextgeneration treatments designed to correct the causative genetic defects of RDEB. PMID:26073463

  3. Coexistence of acquired hemophilia A and epidermolysis bullosa acquisita: Two case reports and published work review.

    PubMed

    Yan, Tian-Meng; He, Chun-Xia; Hua, Bao-Lai; Li, Li; Jin, Hong-Zhong; Liu, Yue-Hua; Zuo, Ya-Gang

    2017-01-01

    Epidermolysis bullosa acquisita (EBA) is a rare chronic subepidermal bullous autoimmune disease. The occurrence of acquired hemophilia A (AHA) is low and so the coexistence of EBA and AHA is extremely rare. We herein described a case of EBA coexisting with AHA and a case of EBA coexisting with AHA and hepatitis B. These EBA may be related to the pathogenesis of AHA. In this study, we analyzed the clinical features in the two Chinese cases of EBA coexisting with AHA, and found esophageal hemorrhage and hematemesis were the main symptoms of both patients. Cyclosporin, prednisone and lamivudine effectively control EBA with AHA and hepatitis B. The dose of cyclosporin should be more than 4 mg/kg per day and the period of treatment should be longer than 5 months to reduce the risk of EBA co-occurring with AHA. © 2016 Japanese Dermatological Association.

  4. Childhood epidermolysis bullosa acquisita during squaric acid dibutyl ester immunotherapy for alopecia areata.

    PubMed

    Guerra, L; Pacifico, V; Calabresi, V; De Luca, N; Castiglia, D; Angelo, C; Zambruno, G; Di Zenzo, G

    2017-02-01

    Epidermolysis bullosa acquisita (EBA) is a rare acquired subepidermal blistering disease associated with autoantibodies against type VII collagen. Although EBA manifests more frequently in adults, it can occur in childhood. We describe a 6-year-old boy who developed the inflammatory variant of EBA shortly after initiation of immunotherapy with squaric acid dibutyl ester (SADBE) for scalp alopecia areata. The disease rapidly regressed following SADBE discontinuation and starting combined steroid and dapsone therapy, and never recurred after treatment tapering and withdrawal. The association of EBA with other autoimmune diseases is common, but EBA occurring during alopecia areata has not been described previously. The development of EBA during SADBE treatment is also notable: the clinical history and therapeutic response in our patient point to a possible role of SADBE in EBA onset. © 2016 British Association of Dermatologists.

  5. Quality of life among adults with epidermolysis bullosa living with a gastrostomy tube since childhood.

    PubMed

    Hubbard, Lynne D; Mayre-Chilton, Kattya

    2015-03-01

    Epidermolysis bullosa (EB) is a rare genetic condition characterized by blistering to the skin and internal mucous membranes arising from mild mechanical trauma. The impact on those affected can be significant. They might have increased nutritional requirements because of blistering, chronic wounds, infection, and loss of exudates, and nutritional intake might be compromised because of oropharyngeal blistering and strictures, resulting in malnutrition in many patients. Placement of gastrostomy tubes can help some patients meet nutritional requirements. We report a recent study on how EB patients and their families approached the issue of whether to have a gastrostomy tube placed and how such tubes affect quality of life. Our findings include important insights for clinicians and families about how patients experience life with a gastrostomy. We show how the process of consent can be improved and how patients with a gastrostomy tube can feel more in control of their lives.

  6. Acral Peeling Skin Syndrome Resembling Epidermolysis Bullosa Simplex in a 10-Month-Old Boy

    PubMed Central

    Kavaklieva, S.; Yordanova, I.; Bruckner-Tuderman, L.; Has, C.

    2013-01-01

    The acral peeling skin syndrome (APSS) is a rare autosomal recessive disorder clinically characterized by asymptomatic desquamation of the skin limited to the hands and feet and histologically by cleavage at the stratum granulosum and stratum corneum level [Kiritsi et al.: J Invest Dermatol 2010;130:1741–1746]. We report on a 10-month-old boy with a history of skin peeling limited to the hands and feet since 2 months of age. Clinical examination revealed erythematous erosions with peripheral desquamation and flaccid blisters. DNA mutation analysis detected two heterozygous TGM5 mutations: c.2T>C, p.M1T in exon 1 and c.337G>T, p.G113C in exon 3 in keeping with the diagnosis of APSS. The clinical presentation of APSS alone might be confusing and strongly resemble epidermolysis bullosa simplex making the differential diagnosis difficult. PMID:24019772

  7. A case of non-hallopeau-siemens recessive dystrophic epidermolysis bullosa.

    PubMed

    Kang, Gyo Shin; Ko, Woo Tae; Kim, Jae Hong; Choi, Sung Min; Kim, Ae Suk; Kim, Dong Hoon; Suh, Moo Kyu

    2009-02-01

    Dystrophic epidermolysis bullosa (DEB) is a rare group of heritable mechanobullous disorders that are characterized by blistering and scarring of the skin and mucosae and these lesions are induced by minor trauma, DEB is also associated with nail dystrophy. DEB can be inherited either in an autosomal recessive or dominant fashion. Regardless of the mode of inheritance, DEB is caused by defects of the ultrastructural entity known as the anchoring fibril, which results in separation of the sublamina densa. Recessive DEB (RDEB) is classified into Hallopeau-Siemens and non-Hallopeau-Siemens. We herein report on a case of non-Hallopeau-Siemens RDEB and there was no family history of this malady, and we present the clinical, histological and electron microscopy findings.

  8. Expanding the histologic spectrum of angina bullosa hemorrhagica: report of one case.

    PubMed

    Kurban, Mazen; Kibbi, Abdul-Ghani; Ghosn, Samer

    2007-10-01

    Angina bullosa hemorrhagica (ABH) is a rarely described phenomenon in the dermatology/dermatopathology literature. It is a self-limited condition occurring exclusively in the oral mucosa characterized clinically by tense hemorrhagic blisters that heal without any sequelae and histologically by a pauci-inflammatory subepithelial hemorrhagic bulla with occasional lymphocytic infiltrate.A 24-year-old healthy woman presented with a 4-month history of recurrent tense blisters over the buccal mucosa which lasted for a few days and resolved without scarring. Histopathology revealed a hemorrhagic subepithelial bulla containing numerous neutrophils with a moderately dense superficial perivascular and interstitial neutrophilic infiltrate. Direct immunofluorescence studies were negative. Based on these findings, the diagnosis of ABH was made. To the best of our knowledge, this is the first report of ABH mimicking histologically neutrophil-rich subepithelial blistering disorders.

  9. Maintenance Hemodialysis Using Native Arteriovenous Fistula in a Patient with Severe Generalized Recessive Dystrophic Epidermolysis Bullosa

    PubMed Central

    Ito, Takayasu; Ishikawa, Eiji; Matsuo, Hiroshi; Fujimoto, Mika; Murata, Tomohiro; Isoda, Kenichi; Mizutani, Hitoshi; Ito, Masaaki

    2016-01-01

    Renal failure and infectious disease are strongly associated with morbidity and mortality in patients with severe generalized recessive dystrophic epidermolysis bullosa (RDEB-sev gen). However, it is reportedly difficult to introduce hemodialysis with an arteriovenous fistula (AVF). We encountered a 32-year-old man with RDEB-sev gen in whom hemodialysis with a native AVF was introduced that favorably affected his long-term survival. This patient eventually died because of cachexia related to the recurrence of cutaneous squamous cell carcinoma 51 months after hemodialysis introduction. We believe that in this patient, the frequency of vascular access troubles related to infection or reduction of blood flow was probably low as a result of hemodialysis with his native AVF. Thus, it seems likely that patients with RDEB-sev gen with end stage kidney disease who are on hemodialysis can be successfully managed with a native AVF. PMID:27722157

  10. First report of junctional epidermolysis bullosa (JEB) in the Italian draft horse.

    PubMed

    Cappelli, Katia; Brachelente, Chiara; Passamonti, Fabrizio; Flati, Alessandro; Silvestrelli, Maurizio; Capomaccio, Stefano

    2015-03-10

    Epitheliogenesis imperfecta in horses was first recognized at the beginning of the 20th century when it was proposed that the disease could have a genetic cause and an autosomal recessive inheritance pattern. Electron microscopy studies confirmed that the lesions were characterized by a defect in the lamina propria and the disease was therefore reclassified as epidermolysis bullosa. Molecular studies targeted two mutations affecting genes involved in dermal-epidermal junction: an insertion in LAMC2 in Belgians and other draft breeds and one large deletion in LAMA3 in American Saddlebred. A mechanobullous disease was suspected in a newborn, Italian draft horse foal, which presented with multifocal to coalescing erosions and ulceration on the distal extremities. Histological examination of skin biopsies revealed a subepidermal cleft formation and transmission electron microscopy demonstrated that the lamina densa of the basement membrane remained attached to the dermis. According to clinical, histological and ultrastructural findings, a diagnosis of junctional epidermolysis bullosa (JEB) was made. Genetic tests confirmed the presence of 1368insC in LAMC2 in the foal and its relatives. This is the first report of JEB in Italy. The disease was characterized by typical macroscopic, histologic and ultrastructural findings. Genetic tests confirmed the presence of the 1368insC in LAMC2 in this case: further investigations are required to assess if the mutation could be present at a low frequency in the Italian draft horse population. Atypical breeding practices are responsible in this case and played a role as odds enhancer for unfavourable alleles. Identification of carriers is fundamental in order to prevent economic loss for the horse industry.

  11. Pain and quality of life evaluation in patients with localized epidermolysis bullosa simplex.

    PubMed

    Brun, Jennifer; Chiaverini, Christine; Devos, Caroline; Leclerc-Mercier, Stéphanie; Mazereeuw, Juliette; Bourrat, Emmanuelle; Maruani, Annabel; Mallet, Stéphanie; Abasq, Claire; Phan, Alice; Vabres, Pierre; Martin, Ludovic; Bodemer, Christine; Lagrange, Sylvie; Lacour, Jean-Philippe

    2017-06-28

    A localized form of epidermolysis bullosa simplex (EBS-l) is considered one of the mildest forms of epidermolysis bullosa (EB), with blisters limited to the palms and soles. However, these lesions can be very painful. The aim of the study was to characterize pain in patients with EBS-l and evaluate its impact on quality of life (QoL). Patients were contacted via the Research Group of the French Society of Pediatric Dermatology and the association of EB patients (DEBRA France). One investigator used a standardized questionnaire that included validated scales for pain and QoL for a telephone interview. We included 57 patients (27 children). All patients had pain: the mean pain on a 10-mm visual analog scale was >5 for most adults (90%) and children ≥8 years old (94%) when blisters were present and for most adults (73%) and about half of the children ≥ age 8 (53%) during dressing changes. Similar results were found for younger patients. Overall, 75% of patients had neuropathic pain; for 55% of children and 73% of adults, the pain had a moderate to severe impact on QOL. Only seven patients used premedication before changing dressings and seven regularly used oral treatment for chronic pain. A total of 21% and 23% of patients used non-steroidal anti-inflammatory drugs and grade 2 analgesics, respectively. These treatments were not effective for neuropathic pain. Six patients tried 5% lidocaine plasters on their feet, with good efficacy. EBS-l patients have frequent and severe pain with neuropathic characteristics. This pain is undertreated and affects QoL.

  12. Retrospective study of the clinical, histologic, and immunologic features of epidermolysis bullosa acquisita in 9 patients.

    PubMed

    Barreiro-Capurro, A; Mascaró-Galy, J M; Iranzo, P

    2013-12-01

    Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease caused by autoantibodies to type VII collagen. The clinical presentation is variable, with skin and mucosal lesions that can cause significant dysfunction. Different treatment options exist, but the results are often unsatisfactory. To review all the cases of epidermolysis bullosa acquisita (EBA) diagnosed at our hospital over a 26-year period. We performed a retrospective review of the clinical, histologic, and immunologic features of EBA in 9 patients. Mean age at presentation was 37 years and 66.67% of the patients were women. EBA occurred in association with malignant tumors, inflammatory bowel disease, and autoimmune disorders. The most common variant was inflammatory EBA (6 of the 9 cases). In all 9 patients, histology revealed a subepidermal blister and direct immunofluorescence showed linear deposits of immunoglobulin G and C3 in the basement membrane zone. Indirect immunofluorescence performed on salt-split skin substrate was positive in 6 patients and showed a dermal pattern in all cases. Five patients were tested for autoantibodies to type VII collagen using enzyme-linked immunosorbent assay, with positive results in 2 cases. Immunoblotting using recombinant noncollagenous domains (NC1) of type VII collagen was positive in all 6 cases in which it was performed. Response to treatment was variable. EBA is a rare disease with a variable clinical presentation that can be confused with that of other subepidermal blistering diseases. Correct diagnosis requires a high level of clinical suspicion and the use of all available diagnostic tests. Thorough evaluation of cutaneous and mucosal involvement and prompt initiation of appropriate treatment will ensure the detection and prevention of dysfunction and treatment-related complications. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  13. Prevalence of specific anti-skin autoantibodies in a cohort of patients with inherited epidermolysis bullosa

    PubMed Central

    2013-01-01

    Background Inherited epidermolysis bullosa (EB) is a group of skin diseases characterized by blistering of the skin and mucous membranes. There are four major types of EB (EB simplex, junctional EB, dystrophic EB and Kindler syndrome) caused by different gene mutations. Dystrophic EB is derived from mutations in the type VII collagen gene (COL7A1), encoding a protein which is the predominant component of the anchoring fibrils at the dermal-epidermal junction. For the first time in literature, we have evaluated the presence of anti-skin autoantibodies in a wider cohort of patients suffering from inherited EB and ascertained whether they may be a marker of disease activity. Methods Sera from patients with inherited EB, 17 with recessive dystrophic EB (RDEB), 10 with EB simplex (EBS) were analysed. As much as 20 patients with pemphigus vulgaris, 21 patients with bullous pemphigoid and 20 healthy subjects were used as controls. Anti-skin autoantibodies were tested in all samples with the Indirect Immunofluorescence (IIF) method and the currently available ELISA method in order to detect anti-type VII collagen, anti-BP180 and anti-BP230 autoantibodies. Results The mean concentrations of anti-type VII collagen autoantibodies titres, anti-BP180 and anti-BP230 autoantibodies were statistically higher in RDEB patients than in EBS patients. The sensitivity and specificity of the anti-type VII collagen ELISA test were 88.2% and 96.7%. The Birmingham Epidermolysis Bullosa Severity score, which is used to evaluate the severity of the disease, correlated with anti-skin autoantibodies titres. Conclusions The precise pathogenic role of circulating anti-skin autoantibodies in RDEB is unclear. There is a higher prevalence of both anti-type VII collagen and other autoantibodies in patients with RDEB, but their presence can be interpreted as an epiphenomenon. PMID:24007552

  14. Association of Epidermolysis Bullosa Simplex With Mottled Pigmentation and EXPH5 Mutations.

    PubMed

    Turcan, Iana; Pasmooij, Anna M G; Van den Akker, Peter C; Lemmink, Henny; Sinke, Richard J; Jonkman, Marcel F

    2016-10-01

    Epidermolysis bullosa simplex (EBS) is a group of clinically and genetically diverse mechanobullous genodermatoses characterized by the fragility of skin and mucous membranes. Recently, mutations in EXPH5 encoding exophilin-5 (also known as Slac2-b, an effector protein involved in intracellular vesicle trafficking and exosome secretion) have been implicated in the pathophysiology of EBS. Herein, we report a novel homozygous nonsense mutation in EXPH5 responsible for an EBS subtype with mottled pigmentation. To identify the gene mutation(s) accountable for the mottled pigmentation phenotype in a patient with suspected inherited skin fragility disorder. Data for this case report were acquired in an outpatient clinic and concern a referral from the primary care physician to the national Center for Blistering Diseases in The Netherlands. Data were acquired and analyzed from 2014 to 2016. Clinical examination and investigation were performed of the molecular basis of patient's skin fragility and mottled pigmentation phenotype. Electron microscopy studies described the underlying abnormalities on an ultrastructural level. The clinical phenotype is characterized by mild generalized skin fragility, trauma-induced skin blistering since infancy, and development of remarkable diffuse mottled pigmentation on the trunk and proximal extremities. Sequencing the complete set of genes associated with epidermolysis bullosa revealed a homozygous nonsense mutation in exon 6 of EXPH5: c.3917C>G, p.Ser1306*. Electron microscopy revealed disruption of keratin filament cytoskeleton and accumulation of melanosomes in a disordered distribution in the keratinocytes. To our knowledge, the current study illustrates the first clinically well-documented, mottled pigmentation phenotype related to a novel EXPH5 mutation. In addition, by means of electron microscopy image analysis, it proposes a hypothesis for the pigmentary changes in this rare autosomal recessive EBS subtype. These findings

  15. Conditional depletion of mast cells has no impact on the severity of experimental epidermolysis bullosa acquisita.

    PubMed

    Kasprick, Anika; Yu, Xinhua; Scholten, Julia; Hartmann, Karin; Pas, Hendri H; Zillikens, Detlef; Ludwig, Ralf J; Petersen, Frank

    2015-05-01

    The role of mast cells (MCs) in autoimmunity is the matter of an intensive scientific debate. Based on observations in different MC-deficient mouse strains, MCs are considered as fundamental players in autoimmune diseases. However, most recent data suggest that the outcome of such diseases is strongly affected by the individual mouse strain used. By the use of two c-Kit mutant MC-deficient mouse strains and one c-Kit-independent strain, we here investigated the role of MCs in a systemic Ab transfer model of epidermolysis bullosa acquisita, a subepidermal autoimmune blistering skin disease characterized by autoantibodies against type VII collagen. While C57BL/6J-Kit(W-sh/W-sh) mice developed an unexpected increased blistering phenotype, no significant differences to WT controls were seen in WBB6F1 -Kit(W/W-v) or the novel Mcpt5-Cre iDTR animals. Interestingly, in a local Ab transfer model, which induces a localized disease, we showed that application of high concentrations of anti-COL7 (where COL7 is type VII collagen) Abs induced MC activation and MC-dependent edema formation that did, however, not contribute to blister induction. Our results indicate that in the autoimmune disorder epidermolysis bullosa acquisita MCs do not contribute to the immune-mediated tissue injury. Modern c-Kit mutant-independent MC-deficient mouse strains will help to further redefine the role of MCs in autoimmunity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. 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

  17. Molecular studies of an impetigo bullosa epidemic in full-term infants.

    PubMed

    Jursa-Kulesza, Joanna; Kordek, Agnieszka; Kopron, Katarzyna; Wojciuk, Bartosz; Giedrys-Kalemba, Stefania

    2009-01-01

    Carriers of Staphylococcus aureus strains can be the source of epidemic infection for patients. A molecular epidemiological analysis of an impetigo bullosa outbreak in a neonatal ward was performed in order to determine a potential source of the infection and possible routes of subsequent spreading of the epidemic strain. The genetic relatedness of S. aureus strains isolated from 6 neonates with epidermal lesions and from 21 staff members was verified by the pulsed field gel electrophoresis (PFGE) method. Additionally, detection of eta and etb genes of S. aureus strains using PCR was performed. None of the infected newborns' mothers was a carrier. Seven strains, 6 isolated from the newborns and 1 taken from a midwife, showed the same restriction pattern, i.e. type A. In the other 20 health care workers colonized with S. aureus, 3 genetic types could be distinguished, i.e. B (2), C (7) and D (2), as well as 9 strains with unique PFGE patterns. The eta gene detected in 7 strains belonged to the genetic type A; there was no etb gene in any of the 27 S. aureus isolates. The presence of the same genetic type A of S. aureus in the infected newborns is a factor which indicates that the impetigo bullosa was a hospital infection. A probable source of the infection was a midwife who was colonized with the same S. aureus type. She was present at the birth of the first infected newborn. Today, molecular methods are essential for prompt recognition of an epidemic and implementation of appropriate infection control strategies. Copyright 2009 S. Karger AG, Basel.

  18. 180-kD bullous pemphigoid antigen (BP180) is deficient in generalized atrophic benign epidermolysis bullosa.

    PubMed Central

    Jonkman, M F; de Jong, M C; Heeres, K; Pas, H H; van der Meer, J B; Owaribe, K; Martinez de Velasco, A M; Niessen, C M; Sonnenberg, A

    1995-01-01

    Generalized atrophic benign epidermolysis bullosa (GABEB) is a form of nonlethal junctional epidermolysis bullosa characterized by universal alopecia and atrophy of the skin. We report a deficiency of the 180-kD bullous pemphigoid antigen in three patients with GABEB from unrelated families. We screened specimens of clinically normal skin from nine junctional epidermolysis bullosa patients (3 GABEB, 4 lethal, 1 cicatricial, 1 pretibial) by immunofluorescence using monoclonal antibodies to the 180-kD and 230-kD bullous pemphigoid antigens (BP180 and BP230). In the skin of the three GABEB patients there was no reactivity with antibodies to BP180, whereas staining for BP230 was normal. In the skin of the other six, non-GABEB patients, included in this study the expression of BP180 and BP230 was normal. Immunoblot analysis of cultured keratinocytes from one of the GABEB patients also failed to detect BP180 antigen, whereas BP230 was present in normal amounts. The deficient expression of BP180 is reflected in the RNA message, as in Northern blot analysis a reduced amount of BP180 transcripts, although of normal length, were detected. Interestingly, in another GABEB patient there were not-involved areas of skin, in which blistering could not be induced by rubbing. Biopsy material from these areas showed interrupted staining for BP180. There was no staining for BP180 in areas of clinically normal but involved skin of this patient. In conclusion, this study reveals that the BP180 antigen is deficient and the BP180 mRNA is reduced in generalized atrophic benign epidermolysis bullosa. Images PMID:7883981

  19. A case of mixed bullous disease of epidermolysis bullosa acquisita and linear IgA bullous dermatosis.

    PubMed

    Osawa, Masumi; Demitsu, Toshio; Toda, Sunao; Yokokura, Hideto; Umemoto, Naoka; Yamada, Tomoko; Yoneda, Kozo; Kakurai, Maki; Yoshida, Mariko; Hashimoto, Takashi

    2005-01-01

    A 75-year-old Japanese male visited us with bullous eruptions on the extremities. Physical examination revealed large bullae on the hands, lower legs and feet. The oral mucosa was also involved. Histology disclosed subepidermal blister with inflammatory cell infiltrates in the dermis. Direct immunofluorescence showed deposits of IgG and IgA at the cutaneous basement membrane zone. Indirect immunofluorescence on 1 M NaCl-split human skin sections demonstrated that the patient's IgG antibodies reacted with the dermal side of the split, while IgA antibodies reacted with the epidermal side. Immunoblotting showed that the patient's serum reacted with the NC1 domain of type VII collagen (290-kDa epidermolysis bullosa acquisita antigen) as well as the 120-kDa linear IgA bullous dermatosis antigen, LAD-1. Systemic prednisolone resulted in a favorable response. From the clinicopathological findings, the present case is not consistent with either epidermolysis bullosa acquisita or IgA bullous dermatosis. Therefore, we regarded the case as mixed bullous disease of epidermolysis bullosa acquisita and linear IgA bullous dermatosis. Such a case has not been previously reported.

  20. Geosmithia argillacea: An Emerging Cause of Invasive Mycosis in Human Chronic Granulomatous Disease

    PubMed Central

    Challipalli, Malliswari; Anderson, Victoria; Shea, Yvonne R.; Marciano, Beatriz; Hilligoss, Dianne; Marquesen, Martha; DeCastro, Rosamma; Liu, Yen-chun; Sutton, Deanna A.; Wickes, Brian L.; Kammeyer, Patricia L.; Sigler, Lynne; Sullivan, Kathleen; Kang, Elizabeth M.; Malech, Harry L.; Holland, Steven M.; Zelazny, Adrian M.

    2011-01-01

    Background. Chronic granulomatous disease (CGD) is an inherited disorder of the nicotinamide adenine dinucleotide phosphate oxidase that leads to defective production of microbicidal superoxide and other oxidative radicals, resulting in increased susceptibility to invasive infections, especially those due to fungi. Methods. Geosmithia argillacea was identified from cultured isolates by genomic sequencing of the internal transcribed spacer region. Isolates previously identified as Paecilomyces variotii, a filamentous fungus closely resembling G. argillacea, were also examined. Results. We identified G. argillacea as the cause of invasive mycosis in 7 CGD patients. In 5 cases, the fungus had been previously identified morphologically as P. variotii. All patients had pulmonary lesions; 1 had disseminated lesions following inhalational pneumonia. Infections involved the chest wall and contiguous ribs in 2 patients and disseminated to the brain in 1 patient. Four patients with pneumonia underwent surgical intervention. All patients responded poorly to medical treatment, and 3 died. Conclusions. We report the first cases of invasive mycosis caused by G. argillacea in CGD patients. G. argillacea infections in CGD are often refractory and severe with a high fatality rate. Surgical intervention has been effective in some cases. G. argillacea is a previously underappreciated and frequently misidentified pathogen in CGD that should be excluded when P. variotii is identified morphologically. PMID:21367720

  1. Systemic mycosis in a California sea lion (Zalophus californianus) with detection of cystofilobasidiales DNA.

    PubMed

    Field, Cara L; Tuttle, Allison D; Sidor, Inga F; Nyaoke, Akinyi; Deering, Kathleen M; Gilbert-Marcheterre, Kelly; Risatti, Guillermo; Spoon, Tracey; Meegan, Jenny; Romano, Tracy A; Frasca, Salvatore; Dunn, J Lawrence

    2012-03-01

    A 6-yr-old, intact male California sea lion (Zalophus californianus) with a systemic mycosis died after 5 wk of antifungal drug therapy. Antemortem clinical findings included hind flipper swelling, ring-lesions on skin of the flippers, and dermal nodules that increased in size and number spreading from the hind flippers and ventral abdomen to the foreflippers and muzzle. Lesions were accompanied by severe lymphadenopathy and development of systemic clinical signs despite therapy using itraconazole and later voriconazole. Histopathologic evaluation of biopsies revealed granulomatous dermatitis due to infection by fungus-producing yeast cells in tissue. Isolation attempts, using biopsied skin and tissue samples collected at necropsy, failed to yield growth of a fungus producing yeast cells like those in histologic section. Consensus polymerase chain reaction (PCR) tests of biopsied skin for fungal DNA produced an amplicon having significant sequence identity with a Cystofilobasidiales, a fungus belonging to a subclade that includes several Cryptococcus spp. Histopathologic evaluation of necropsy tissues revealed a systemic mycosis with yeast cells disseminated throughout subcutis, lymph nodes, and viscera. Hepatic necrosis was identified associated with acute liver failure, possibly from the voriconazole administration. This is the first report documenting the clinical presentation, treatment, and pathologic findings of infection associated with Cystofilobasidiales in a marine mammal and serves to expand the understanding of mycoses in pinnipeds.

  2. [Species distribution and antifungal susceptibility of Candida spp. causing superficial mycosis. Coro, Falcon state, Venezuela].

    PubMed

    Saúl-García, Yotsabeth; Humbría-García, Leyla; Hernández-Valles, Rosaura

    2015-09-01

    Candida species other than C. albicans are often described as causative agents of superficial mycosis and are more resistant to treatment with azoles. In order to determine the distribution of species and in vitro antifungal susceptibility of Candida spp., one ambispective study, which analyzed 18 yeast isolates obtained from samples from patients diagnosed with superficial mycosis, was performed. Taxonomic identification was performed by macroscopic visualization of the growth characteristics in chromogenic agar and by conventional methods. The susceptibility to fluconazole and voriconazole was evaluated by the disc diffusion method. Most of the isolates (88.8%), came from nail samples. C. parapsilosis was the most common species, followed by C. tropicalis, C. albicans and C. krusei, which confirmed the prevalence of non-albicans species as a cause of superficial mycoses. The pattern of susceptibility to fluconazole and voriconazole was similar: all isolates of C. parapsilosis and C. albicans were susceptible, while 83.3% of C. tropicalis showed sensitivity to both antifungals. C. krusei, fluconazole-resistant species showed intermediate susceptibility io voriconazole. The use of chromogenic agar allowed to detect mixed infections in nail samples, involving Candida spp. and C. tropicalis in one case, the latter with resistance to both fluconazole and voriconazole. The results demonstrate the importance of species identification and susceptibility testing to avoid therapeutic failures in superficial mycoses.

  3. A glutamate to lysine mutation at the end of 2B rod domain of keratin 2e gene in ichthyosis bullosa of Siemens.

    PubMed

    Yang, J M; Lee, E S; Kang, H J; Choi, G S; Yoneda, K; Jung, S Y; Park, K B; Steinert, P M; Lee, E S

    1998-11-01

    Ichthyosis bullosa of Siemens is a rare autosomal dominant skin disorder whose clinical findings are quite similar to those of epidermolytic hyperkeratosis. The differences between those two diseases include absence of erythroderma and different distributions in the skin in ichthyosis bullosa of Siemens. Recent studies have confirmed that ichthyosis bullosa of Siemens is caused by the mutation in the keratin 2e (K2e) gene, which is expressed in the upper spinous and granular layers. We have identified a sporadic case of ichthyosis bullosa of Siemens; based on diagnosis by histopathological findings, the K2e gene of the patient was analysed. Direct sequencing of PCR products revealed a single base change in sequences encoding the highly conserved end of the 2B rod domain segment of the K2e gene. This mutation results in substitution of the codon for glutamic acid by a codon for lysine in position 493 in K2e (E493K). Mutations of the K2e gene involving five different residue positions (Q187P, T485P, L490P, E493D, E493K and E494K) are known to cause ichthyosis bullosa of Siemens. Of these sites, E493, which is conserved in type I and type II keratin genes, is the most frequently altered amino acid in the K2e gene. These data together suggest that this codon constitutes a hot spot for mutations in the K2e gene.

  4. Epidermolysis bullosa

    MedlinePlus

    ... anemia Culture to check for bacterial infection if wounds are healing poorly Upper endoscopy or an upper GI series ... crusted or raw. You might need regular whirlpool therapy and to apply antibiotic ointments to wound-like areas. Your provider will let you know ...

  5. Pain care for patients with epidermolysis bullosa: best care practice guidelines.

    PubMed

    Goldschneider, Kenneth R; Good, Julie; Harrop, Emily; Liossi, Christina; Lynch-Jordan, Anne; Martinez, Anna E; Maxwell, Lynne G; Stanko-Lopp, Danette

    2014-10-09

    Inherited epidermolysis bullosa (EB) comprises a group of rare disorders that have multi-system effects and patients present with a number of both acute and chronic pain care needs. Effects on quality of life are substantial. Pain and itching are burdensome daily problems. Experience with, and knowledge of, the best pain and itch care for these patients is minimal. Evidence-based best care practice guidelines are needed to establish a base of knowledge and practice for practitioners of many disciplines to improve the quality of life for both adult and pediatric patients with EB. The process was begun at the request of Dystrophic Epidermolysis Bullosa Research Association International (DEBRA International), an organization dedicated to improvement of care, research and dissemination of knowledge for EB patients worldwide. An international panel of experts in pain and palliative care who have extensive experience caring for patients with EB was assembled. Literature was reviewed and systematically evaluated. For areas of care without direct evidence, clinically relevant literature was assessed, and rounds of consensus building were conducted. The process involved a face-to-face consensus meeting that involved a family representative and methodologist, as well as the panel of clinical experts. During development, EB family input was obtained and the document was reviewed by a wide variety of experts representing several disciplines related to the care of patients with EB. The first evidence-based care guidelines for the care of pain in EB were produced. The guidelines are clinically relevant for care of patients of all subtypes and ages, and apply to practitioners of all disciplines involved in the care of patients with EB. When the evidence suggests that the diagnosis or treatment of painful conditions differs between adults and children, it will be so noted. Evidence-based care guidelines are a means of standardizing optimal care for EB patients, whose disease is

  6. White-Nose Syndrome: Human Activity in the Emergence of an Extirpating Mycosis.

    PubMed

    Reynolds, Hannah T; Barton, Hazel A

    2013-12-01

    In winter 2006, the bat population in Howe Cave, in central New York State, USA, contained a number of bats displaying an unusual white substance on their muzzles. The following year, numerous bats in four surrounding caves displayed unusual winter hibernation behavior, including day flying and entrance roosting. A number of bats were found dead and dying, and all demonstrated a white, powdery substance on their muzzles, ears, and wing membranes, which was later identified as the conidia of a previously undescribed fungal pathogen, Geomyces destructans. The growth of the conidia gave infected bats the appearance of having dunked their faces into powdered sugar. The disease was named white-nose syndrome and represents an emerging zoonotic mycosis, likely introduced through human activities, which has led to a precipitous decline in North American bat species.

  7. Guttural pouch mycosis in horses: a retrospective study of 28 cases.

    PubMed

    Dobesova, O; Schwarz, B; Velde, K; Jahn, P; Zert, Z; Bezdekova, B

    2012-12-01

    The medical records of 28 horses with guttural pouch mycosis were reviewed. The most commonly observed clinical signs were nasal discharge, epistaxis, dysphagia and/or cough. All 28 horses had the disease unilaterally, however, in five of them, it had spread into the contralateral pouch via the mesial septum. Three horses were treated medically, 11 horses underwent surgery and seven horses were treated both medically and surgically. Fifty percent of horses (14/28) were euthanased or died, fifty percent of horses (14/28) survived. There was no significant correlation between treatment method (medical, surgical, combination) and survival rate. The most common reason for euthanasia was dysphagia due to pharyngeal dysfunction. There was a highly significant correlation between the presence of dysphagia and non-survival (p=0.008).

  8. Algorithm of clinical protocol lowering the risk of systemic Mycosis infections in allografts recipients.

    PubMed

    Swoboda-Kopec, E; Netsvyetayeva, I; Paczek, L; Dabkowska, M; Kwiatkowski, A; Jaworska-Zaremba, M; Mierzwinska-Nastalska, E; Sikora, M; Blachnio, S; Mlynarczyk, G; Fiedor, P

    2009-10-01

    The aim of the study was to describe a diagnostic protocol to lower the risk of a mycotic invasive infection among allotransplant recipients and to suggest the use of preoperative prophylaxis and/or empiric therapy. We chose a group of 268 allograft recipients with transient or constant yeast colonization or confirmed yeast infection. Among 7744 clinical samples, 475 were positive for fungi. We used conventional fungal laboratory diagnosis, enzymatic activity tests, serologic tests, molecular diagnosis of samples from sterile body sites, and histopathologic examinations. The following clinical samples were examined: blood samples; swabs from mouth lesions, throat, and rectum; and sputum, urine, and fecal samples from kidney transplant recipients and simultaneous pancreas-kidney transplantation recipients who are highly predisposed to mycotic infections. We established microbiologic criteria of a systemic mycosis and principles to distinguish colonization from infection.

  9. [Allergic bronchopulmonary mycosis induced by Schizophyllum commune--case report and review of the literature].

    PubMed

    Amemiya, Yuka; Shirai, Ryo; Tokimatsu, Issei; Oka, Hiroaki; Iwata, Atsuko; Otani, Satoshi; Umeki, Kenji; Sakashita, Hiroyuki; Ishii, Hiroshi; Gendo, Yoshiko; Kishi, Kenji; Hiramatsu, Kazufumi; Kadota, Jun-ichi

    2009-08-01

    A 55-year-old man was admitted to our hospital because of pyrexia, cough and sputum. He suffered from bronchial asthma. Chest X-ray showed infiltrates in the left upper and right lower lung fields. Chest CT scans showed mucoid impaction and consolidation predominantly in the left upper lobe. Laboratory tests showed peripheral eosinophilia, elevated level of serum IgE, and the increased eosinophils in his sputum. Schizophyllum commune was isolated from the bronchoscopically-removed mucous plug. A diagnosis of allergic bronchopulmonary mycosis (ABPM) due to S. commune was made. Simultaneous daily administration of 400 mg itraconazole (ITCZ) and corticosteroid (prednisolone; 30 mg daily) provided sufficient improvement. However recurrence was recognized on chest CT scan findings one year later. There are not enough case reports concerning S. commune-induced ABPM to establish a therapeutic approach to the condition.

  10. Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF Treatment

    PubMed Central

    Hirose, Misa; Kasprick, Anika; Beltsiou, Foteini; Dieckhoff, Katharina Schulze; Schulze, Franziska Sophie; Samavedam, Unni KJSRL; Hundt, Jennifer E; Pas, Hendri H; Jonkman, Marcel F; Schmidt, Enno; Kalies, Kathrin; Zillikens, Detlef; Ludwig, Ralf J; Bieber, Katja

    2016-01-01

    Epidermolysis bullosa acquisita (EBA) is a difficult-to-treat subepidermal autoimmune blistering skin disease (AIBD) with circulating and tissue-bound anti–type VII collagen antibodies. Different reports have indicated increased concentration of tumor necrosis factor α (TNF) in the serum and blister fluid of patients with subepidermal AIBD. Furthermore, successful anti-TNF treatment has been reported for individual patients with AIBD. Here we show that in mice, induction of experimental EBA by repeated injections of rabbit anti-mouse type VII collagen antibodies led to increased expression of TNF in skin, as determined by real-time polymerase chain reaction (PCR) and immunohistochemistry. To investigate whether the increased TNF expression is of functional relevance in experimental EBA, we inhibited TNF function using the soluble TNF receptor fusion protein etanercept (Enbrel) or a monoclonal antibody to murine TNF. Interestingly, mice that received either of these treatments showed significantly milder disease progression than controls. In addition, immunohistochemical staining demonstrated reduced numbers of macrophages in lesional skin in mice treated with TNF inhibitors compared with controls. Furthermore, etanercept treatment significantly reduced disease progression in immunization-induced EBA. In conclusion, increased expression of TNF in experimental EBA is of functional relevance, as both the prophylactic blockade of TNF and the therapeutic use of etanercept impaired induction and progression of experimental EBA. Thus, TNF is likely to serve as a new therapeutic target for EBA and AIBDs with a similar pathogenesis. PMID:27999842

  11. Novel and emerging therapies in the treatment of recessive dystrophic epidermolysis bullosa

    PubMed Central

    Rashidghamat, Ellie; McGrath, John A.

    2017-01-01

    Summary Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of inherited blistering diseases that affects ∼ 500,000 people worldwide. Clinically, individuals with EB have fragile skin and are susceptible to blistering following minimal trauma, with mucous membrane and other organ involvement in some subtypes. Within the spectrum of EB, ∼ 5% of affected individuals have the clinically more severe recessive dystrophic (RDEB) variant with a prevalence of 8 per one million of the population. RDEB is caused by loss-of-function mutations in the type VII collagen gene, COL7A1, which leads to reduced or absent type VII collagen (C7) and a paucity of structurally effective anchoring fibrils at the dermal-epidermal junction (DEJ). Currently, there is no cure for RDEB, although considerable progress has been made in testing novel treatments including gene therapy (lentiviral and gamma retroviral vectors for COL7A1 supplementation in keratinocytes and fibroblasts), as well as cell therapy (use of allogeneic fibroblasts, mesenchymal stromal cells (MSCs), and bone marrow transplantation (BMT)). Here, we review current treatment modalities available as well as novel and emerging therapies in the treatment of RDEB. Clinical trials of new translational therapies in RDEB offer hope for improved clinical management of patients as well as generating broader lessons for regenerative medicine that could be applicable to other inherited or acquired abnormalities of wound healing or scarring. PMID:28357176

  12. Topography of distinct Staphylococcus aureus types in chronic wounds of patients with epidermolysis bullosa.

    PubMed

    van der Kooi-Pol, Magdalena M; Sadaghian Sadabad, Mehdi; Duipmans, José C; Sabat, Artur J; Stobernack, Tim; Omansen, Till F; Westerhout-Pluister, Gerlinde N; Jonkman, Marcel F; Harmsen, Hermie J M; van Dijl, Jan Maarten

    2013-01-01

    The opportunistic pathogen Staphylococcus aureus is known to interfere with wound healing and represents a significant risk factor for wound infections and invasive disease. It is generally assumed that one individual is predominantly colonized by one S. aureus type. Nevertheless, patients with the genetic blistering disease epidermolysis bullosa (EB) often carry multiple S. aureus types. We therefore investigated whether different S. aureus types are present in individual wounds of EB patients and, if so, how they are spatially distributed. The staphylococcal topography in chronic wounds was mapped by replica-plating of used bandages and subsequent typing of S. aureus isolates. Individual chronic wounds of five patients contained up to six different S. aureus types. Unexpectedly, distinct S. aureus types formed micro-colonies that were located in close proximity and sometimes even overlapped. While some adjacent S. aureus isolates were closely related, others belonged to distinct molecular complexes. We conclude that the general assumption that one individual is predominantly colonized by one type of S. aureus does not apply to chronic wounds of EB patients. We consider this observation important, not only for EB patients, but also for other patients with chronic wounds in view of the potential risk for severe staphylococcal infections.

  13. Transcriptome and ultrastructural changes in dystrophic Epidermolysis bullosa resemble skin aging.

    PubMed

    Breitenbach, Jenny S; Rinnerthaler, Mark; Trost, Andrea; Weber, Manuela; Klausegger, Alfred; Gruber, Christina; Bruckner, Daniela; Reitsamer, Herbert A; Bauer, Johann W; Breitenbach, Michael

    2015-06-01

    The aging process of skin has been investigated recently with respect to mitochondrial function and oxidative stress. We have here observed striking phenotypic and clinical similarity between skin aging and recessive dystrophic Epidermolysis bullosa (RDEB), which is caused by recessive mutations in the gene coding for collagen VII,COL7A1. Ultrastructural changes, defects in wound healing, and inflammation markers are in part shared with aged skin. We have here compared the skin transcriptomes of young adults suffering from RDEB with that of sex- and age-matched healthy probands. In parallel we have compared the skin transcriptome of healthy young adults with that of elderly healthy donors. Quite surprisingly, there was a large overlap of the two gene lists that concerned a limited number of functional protein families. Most prominent among the proteins found are a number of proteins of the cornified envelope or proteins mechanistically involved in cornification and other skin proteins. Further, the overlap list contains a large number of genes with a known role in inflammation. We are documenting some of the most prominent ultrastructural and protein changes by immunofluorescence analysis of skin sections from patients, old individuals, and healthy controls.

  14. Novel KRT14 mutation causing epidermolysis bullosa simplex with variable phenotype.

    PubMed

    Jankowski, Marek; Wertheim-Tysarowska, Katarzyna; Jakubowski, Rafal; Sota, Justyna; Nowak, Wieslaw; Czajkowski, Rafal

    2014-09-01

    About 75% of cases of epidermolysis bullosa simplex result from mutations in KRT5 and KRT14 genes. Here, we report a family with a novel heterozygous missense mutation p.Leu418Gln in the KRT14 gene causing EBS of phenotype varying from EBS-loc to EBS-gen intermed. To the best of our knowledge, the family reported by us is the largest one in which two different phenotypes can be distinguished. The molecular dynamics simulations show that p.Leu418Gln mutation results in clear disruption of intermolecular π-stacking between KRT14:Tyr415 and KRT5:Tyr470, which in turn may affect putative phosphorylation site at KRT14:Thr414. This study further supports the importance of the EIATYR/KLLEGE motif in maintaining structural stability of KRT14:KRT5 heterodimer and indicates that physical properties of introduced amino acid can modulate the disease severity. The results obtained indicate further need of genotype-phenotype studies in EBS. In conclusion, genotype-based prognosis should be given to patients with caution. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. [Current approaches to the morphologic diagnosis of different types of congenital epidermolysis bullosa].

    PubMed

    Smolyannikova, V A; Kubanova, A A; Albanova, V I; Nefedova, M A; Karamova, A E

    Congenital epidermolysis bullosa (CEB) is an extensive group of hereditary skin diseases, the differential diagnosis of which is a challenge due to the rarity of this pathology and the diversity of its clinical manifestations. The determination of the type of CEB makes it possible to estimate its prognosis and to facilitate a prenatal diagnosis. to optimize the morphological diagnosis of different types of CEB. 28 skin biopsies from 14 patients with different types of CEB were investigated. The investigators performed routine histological examination of skin fragments taken from a bullous area and immunofluorescence antigen mapping using the indirect immunofluorescence test (IIFT) with antibodies against structural proteins of the dermal-epidermal junction (laminin α3, β3, and γ2 chains, keratins 5 and 14, types VII and XVII collagen, α6 and β4 integrin subunits, desmoplakin, plectin, kindlin-1, and plakophillin) of the apparently unaffected skin. The intact skin of healthy individuals, which had been obtained during cosmetic operations, was used as controls in IIFT. Immunofluorescence antigen mapping could determine the type of CEB in all cases and in 86% of cases identify the protein, the impaired production of which was responsible for the development of the disease. Immunofluorescence antigen mapping is an integral part of the comprehensive morphological diagnosis of CEB, acting as an intermediate between the morphological verification of CEB diagnosis and the targeted search for mutations by a molecular genetic method.

  16. Defining keratin protein function in skin epithelia: Epidermolysis Bullosa Simplex and its aftermath

    PubMed Central

    Coulombe1, Pierre A.; Lee, Chang-Hun

    2011-01-01

    Epidermolysis bullosa simplex (EBS) is a rare genetic condition typified by superficial bullous lesions following incident frictional trauma to the skin. Most cases of EBS are due to dominantly-acting mutations in keratin 14 (K14) or K5, the type I and II intermediate filament (IF) proteins that co-polymerize to form a pan-cytoplasmic network of 10nm filaments in basal keratinocytes of epidermis and related epithelia. Defects in K5–K14 filament network architecture cause basal keratinocytes to become fragile, and account for their rupture upon exposure to mechanical trauma. The discovery of the etiology and pathophysiology of EBS was intimately linked to the quest for an understanding of the properties and function of keratin filaments in skin epithelia. Since then, continued cross-fertilization between basic science efforts and clinical endeavors has highlighted several additional functional roles for keratin proteins in the skin, suggested new avenues for effective therapies for keratin-based diseases, and expanded our understanding of the remarkable properties of skin as an organ system. PMID:22277943

  17. Host-pathogen interactions in epidermolysis bullosa patients colonized with Staphylococcus aureus.

    PubMed

    van der Kooi-Pol, Magdalena M; Duipmans, José C; Jonkman, Marcel F; van Dijl, Jan Maarten

    2014-03-01

    Patients with the genetic blistering disease epidermolysis bullosa (EB) often have chronic wounds that can become colonized by different bacteria, especially the opportunistic pathogen Staphylococcus aureus. We therefore determined the S. aureus colonization rates in EB patients from the Netherlands by collecting swabs from their anterior nares, throats and wounds. Within a period of ∼2 years, more than 90% of the sampled chronic wounds of EB patients were found to be colonized by S. aureus. Molecular typing revealed that EB patients were not colonized by a single S. aureus type. Rather the S. aureus population structure in the sampled EB patients mirrored the local S. aureus population structure within the Netherlands. Furthermore, multiple types of S. aureus were found in close proximity to each other within individual chronic wounds, indicating that these S. aureus types are not mutually exclusive. Over time, strong fluctuations in the S. aureus types sampled from individual EB patients were observed. This high exposure to different S. aureus types is apparently reflected by high plasma levels of antistaphylococcal IgG's, especially in patients carrying multiple S. aureus types. It remains to be determined to what extent this strong immune response protects EB patients against serious staphylococcal infections. Lastly, further research is needed to define the impact of staphylococcal colonization of chronic wounds on the development, exacerbation and healing of such wounds in patients with EB. Copyright © 2013 Elsevier GmbH. All rights reserved.

  18. Induced Pluripotent Stem Cells from Individuals with Recessive Dystrophic Epidermolysis Bullosa

    PubMed Central

    Tolar, Jakub; Xia, Lily; Riddle, Megan; Lees, Chris J.; Eide, Cindy; McElmurry, Ron T.; Titeux, Matthias; Osborn, Mark J.; Lund, Troy C.; Hovnanian, Alain; Wagner, John E.; Blazar, Bruce R.

    2014-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited blistering skin disorder caused by mutations in the COL7A1 gene-encoding type VII collagen (Col7), the major component of anchoring fibrils at the dermal-epidermal junction. Individuals with RDEB develop painful blisters and mucosal erosions, and currently there are no effective forms of therapy. Nevertheless, some advances in patient therapy are being made, and cell-based therapies with mesenchymal and hematopoietic cells have shown promise in early clinical trials. To establish a foundation for personalized, gene-corrected, patient-specific cell transfer, we generated induced pluripotent stem cells from three subjects with RDEB (RDEB iPS cells). We found that Col7 was not required for stem cell renewal and that RDEB iPS cells could be differentiated to both hematopoietic and non-hematopoietic lineages. The specific epigenetic profile associated with de-differentiation of RDEB fibroblasts and keratinocytes into RDEB iPS cells was similar to that observed in wild-type iPS cells. Importantly, human wild-type and RDEB iPS cells differentiated in vivo into structures resembling skin. Gene-corrected RDEB iPS cells expressed Col7. These data identify the potential of RDEB iPS cells to generate autologous hematopoietic grafts and skin cells with the inherent capacity to treat the skin and mucosal erosions that typify this genodermatosis. PMID:21124339

  19. A homozygous mutation in keratin 5 is a fully dominant allele responsible for epidermolysis bullosa simplex

    SciTech Connect

    Stephens, K.; Smith, L.; Ehrlich, P.

    1994-09-01

    Molecular, ultrastructural, and clinical analysis of a large family with epidermolysis bullosa simplex (EBS) and multiple consanguineous marriages has identified one affected individual who inherited defective keratin 5 genes from both of her affected parents. EBS are skin blistering disorders caused by abnormal keratin filament assembly or function due to a mutation in either of the two structural proteins keratin 5 or keratin 14. Linkage analysis with DNA markers near each keratin gene demonstrated that the defect in this family mapped near keratin 5 (K5) with a LOD score of 7.60, {theta}=0.0 for the proximal marker D12S14. Sequencing of the K5 gene identified an Asn substitution of a highly conserved Lys at codon 173 in the 5{prime} end of the central rod domain. The mutation was found in 33 affected family members but not in 5 unaffected members or 25 unrelated, unaffected individuals. Both linkage and sequence analysis verified that one affected individual was homozygous for the K5 mutation. In this family, clinical examination and analysis of epidermal ultrastructure by electron microscopy were consistent with the Koebner subtype of EBS. Despite the absence of any normal K5 protein in the skin, the clinical and ultrastructural phenotypes of the homozygous individual did not differ significantly from those of affected heteozygous relatives. This K5 mutation is a fully dominant allele.

  20. Distinct Impact of Two Keratin Mutations Causing Epidermolysis Bullosa Simplex on Keratinocyte Adhesion and Stiffness.

    PubMed

    Homberg, Melanie; Ramms, Lena; Schwarz, Nicole; Dreissen, Georg; Leube, Rudolf E; Merkel, Rudolf; Hoffmann, Bernd; Magin, Thomas M

    2015-10-01

    Keratin filaments constitute the major component of the epidermal cytoskeleton from heterodimers of type I and type II keratin subunits. Missense mutations in keratin 5 or keratin 14, highly expressed in the basal epidermis, cause the severe skin blistering disease epidermolysis bullosa simplex (EBS) in humans by rendering the keratin cytoskeleton sensitive to mechanical stress; yet, the mechanisms by which individual mutations cause cell fragility are incompletely understood. Here, we compared the K14p.Arg125Pro with the K5p.Glu477Asp mutation, both giving rise to severe generalized EBS, by stable expression in keratin-free keratinocytes. This revealed distinctly different effects on keratin cytoskeletal organization, in agreement with in vivo observations, thus validating the cell system. Although the K14p.Arg125Pro mutation led to impaired desmosomes, downregulation of desmosomal proteins, and weakened epithelial sheet integrity upon shear stress, the K5p.Glu477Asp mutation did not impair these functions, although causing EBS with squamous cell carcinoma in vivo. Atomic force microscopy demonstrated that K14 mutant cells were even less resistant against deformation compared with keratin-free keratinocytes. Thus, a keratin mutation causing EBS compromises cell stiffness to a greater extent than the lack of keratins. Finally, re-expression of K14 in K14 mutant cells did not rescue the above defects. Collectively, our findings have implications for EBS therapy approaches.

  1. [Anaesthetic management in a paediatric patient with a difficult airway due to epidermolysis bullosa dystrophica].

    PubMed

    Blázquez Gómez, E; Garcés Aletá, A; Monclus Diaz, E; Manen Berga, F; García-Aparicio, L; Ontanilla López, A

    2015-05-01

    Dystrophic epidermolysis bullosa (DEB) is a rare inherited disorder characterized by blistering after minimal trauma. These blisters tend to form dystrophic scars, leading to limiting and life-threatening sequelae. The anaesthetic management of patients with DEB is a challenge, even for the most experienced anaesthesiologists, but basic principles can help us prepare the plan of care. The main goals are to prevent trauma/infection of skin/mucous, and to establish a secure airway without causing bullae. Patient positioning and the instruments used to monitor vital signs and administering anaesthetic agents can cause new lesions. It is advisable to lubricate the instruments and to avoid adhesive material and shearing forces on the skin. Besides the implications of the comorbidities, there is a potential difficult intubation and difficult vascular access. Acute airway obstruction can occur due to airway instrumentation. We report the case of a patient diagnosed with EBD difficult airway and undergoing correction of syndactylyl and dental extractions. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Genetically corrected iPSCs as cell therapy for recessive dystrophic epidermolysis bullosa.

    PubMed

    Wenzel, Daniel; Bayerl, Jonathan; Nyström, Alexander; Bruckner-Tuderman, Leena; Meixner, Arabella; Penninger, Josef M

    2014-11-26

    Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in the gene encoding type VII collagen, resulting in fragile skin and mucous membranes that blister easily in response to mechanical stress. Induced pluripotent stem cells (iPSCs) carry the potential to fundamentally change cell-based therapies for human diseases, in particular for RDEB, for which no effective treatments are available. To provide proof of principle on the applicability of iPSCs for the treatment of RDEB, we developed iPSCs from type VII collagen (Col7a1) mutant mice that exhibited skin fragility and blistering resembling human RDEB. Genetically repaired iPSCs could be differentiated into functional fibroblasts that reexpressed and secreted type VII collagen. Corrected iPSC-derived fibroblasts did not form tumors in vivo and could be traced up to 16 weeks after intradermal injection. Moreover, iPSC-based cell therapy resulted in faithful and long-term restoration of type VII collagen deposition at the epidermal-dermal junction of Col7a1 mutant mice. Intradermal injection of genetically repaired iPSC-derived fibroblasts restored the mechanical resistance to skin blistering in mice with RDEB, suggesting that RDEB skin could be effectively and safely repaired using iPSC-based cell therapy.

  3. Gastrostomy tube feeding in children with epidermolysis bullosa: consideration of key issues.

    PubMed

    Haynes, Lesley; Mellerio, Jemima E; Martinez, Anna E

    2012-01-01

    Complications of severe forms of epidermolysis bullosa (EB) almost invariably lead to chronic malnutrition, jeopardizing immune status, growth, iron status, bone health, wound healing, and quality of life. Although gastrostomy tube (G-tube) feeding has successfully addressed the difficulties of providing nutrition and medications in some children attending our center, others have developed problems such as abdominal distension, poor feed tolerance, and leakage of gastric contents with persistent localized skin ulceration, posing enormous challenges to skin management and nutritional maintenance. Suspicions that G-tube placement and feeding cause or exacerbate these problems has led to a decline in placements at our center over the last 10 years. We therefore recognized that it should not be rejected without due consideration of why some patients seem more prone to complications than others. Thus, information on selected issues and outcomes of G-tube placement was obtained from records of 66 patients undergoing surgery between 1989 and 2008. The complex interrelationships of the sequelae of severe EB, changes in practice over 20 years and lack of data for patients treated early in the series make it impossible to draw firm conclusions at this stage, however, our scrutiny provides valuable information on which to base debate and future studies. It also offers well as useful insights for fellow professionals involved in nutrition support in children with severe EB.

  4. Effects of intravenous immunoglobulins on mice with experimental epidermolysis bullosa acquisita.

    PubMed

    Hirose, Misa; Tiburzy, Benjamin; Ishii, Norito; Pipi, Elena; Wende, Sabina; Rentz, Ellen; Nimmerjahn, Falk; Zillikens, Detlef; Manz, Rudolf A; Ludwig, Ralf J; Kasperkiewicz, Michael

    2015-03-01

    Although well-designed prospective trials are generally lacking, intravenous immunoglobulins (IVIG) seem an effective adjuvant treatment for autoimmune bullous skin diseases. Here, efficacy of IVIG monotherapy was compared with corticosteroid treatment in mice with immunization-induced experimental epidermolysis bullosa acquisita (EBA), an autoimmune bullous skin disease characterized by autoantibodies against type VII collagen. We found that IVIG significantly ameliorated clinical disease severity and skin neutrophil infiltration compared with vehicle-treated mice, whereas methylprednisolone showed comparatively less pronounced effects. Efficacy of IVIG was accompanied by reduced levels of autoantibodies, a shift toward noncomplement-fixing autoantibodies, and lower complement deposition at the dermal-epidermal junction. In addition, peripheral Gr-1-positive cells of IVIG-treated animals showed reduced expression of the activating Fcγ receptor IV, which we recently described as a major mediator of tissue injury in experimental EBA. These data show that treatment with IVIG is superior to systemic corticosteroids in experimental EBA and that the effects of IVIG are pleiotropic involving modulation of both the adaptive and innate immune response, although the detailed mode of action of IVIG in this model remains in need of further elucidation.

  5. Angina bullosa hemorrhagica of the soft palate: a clinical study of 16 cases.

    PubMed

    Horie, Norio; Kawano, Ryutaro; Inaba, Junichi; Numa, Takehiro; Kato, Takao; Nasu, Daisuke; Kaneko, Takahiro; Kudo, Itsuro; Shimoyama, Tetsuo

    2008-03-01

    Angina bullosa hemorrhagica (ABH) is an oral mucosal blood blister that develops without blood dyscrasia or vesiculobullous disorder. Although a minor mucosal trauma has been suggested as a triggering factor for ABH, its etiopathogenesis, especially the causative role of systemic conditions, is largely unknown. We investigated the presence or absence of local factors as well as systemic background disease in 16 patients with ABH arising in the soft palate. All the lesions were solitary, and 75% of them (n = 12) appeared during the ingestion of hard or crispy food. With regard to underlying systemic conditions, hypertension was the most common (n = 6), and asthma, insomnia, diabetes mellitus, rheumatoid arthritis, gastrointestinal disorder and hyperuricemia were also recorded (n = 1 each). Five patients had no significant background disease. There were no recalcitrant or recurrent cases. In conclusion, the present study has revealed that scratching of the oral mucosa during eating plays an important role in the formation of ABH. Hypertension appears to be the most frequent background condition, but its pathogenic relationship with ABH remains speculative, as hypertension is fairly common in adults.

  6. T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita.

    PubMed

    Bieber, Katja; Witte, Mareike; Sun, Shijie; Hundt, Jennifer E; Kalies, Kathrin; Dräger, Sören; Kasprick, Anika; Twelkmeyer, Trix; Manz, Rudolf A; König, Peter; Köhl, Jörg; Zillikens, Detlef; Ludwig, Ralf J

    2016-12-05

    T cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organ-specific autoimmune disease, namely epidermolysis bullosa acquisita (EBA) - characterized and caused by autoantibodies targeting type VII collagen. Specifically, we show that immune complex (IC)-induced inflammation depends on the presence of T cells - a process facilitated by T cell receptor (TCR)γδ and NKT cells. Because tissue damage in IC-induced inflammation is neutrophil-dependent, we further analyze the interplay between T cells and neutrophils in an experimental model of EBA. We demonstrate that T cells not only enhance neutrophil recruitment into the site of inflammation but also interact with neutrophils in lymphatic organs. Collectively, this study shows that T cells amplify the effector phase of antibody-induced tissue inflammation.

  7. Founder mutation in dystonin-e underlying autosomal recessive epidermolysis bullosa simplex in Kuwait.

    PubMed

    Takeichi, T; Nanda, A; Liu, L; Aristodemou, S; McMillan, J R; Sugiura, K; Akiyama, M; Al-Ajmi, H; Simpson, M A; McGrath, J A

    2015-02-01

    Only two homozygous nonsense mutations in the epidermal isoform of the dystonin gene, DST-e, have been reported previously in autosomal recessive epidermolysis bullosa simplex (EBS); the affected pedigrees were Kuwaiti and Iranian. This subtype of EBS is therefore considered to be a rare clinicopathological entity. In this study, we identified four seemingly unrelated Kuwaiti families in which a total of seven individuals had predominantly acral trauma-induced blistering since infancy. All affected individuals were homozygous for the mutation p.Gln1124* in DST-e, the same mutation that was identified in the originally reported family from Kuwait. Haplotype analysis in the five pedigrees (including the previous case) revealed a shared block of ~60 kb of genomic DNA across the site of the mutation, consistent with a founder effect. Most heterozygotes had no clinical abnormalities although one subject had mild transient skin fragility during childhood, an observation noted in the previously reported Iranian pedigree, suggesting that the condition may also be semidominant in some pedigrees rather than purely autosomal recessive. Our study reveals propagation of a mutant ancestral allele in DST-e throughout Kuwait, indicating that this subtype of EBS may be more common in Kuwait, and perhaps other Middle Eastern countries, than is currently appreciated.

  8. Oral health care for patients with epidermolysis bullosa--best clinical practice guidelines.

    PubMed

    Krämer, Susanne M; Serrano, María Concepción; Zillmann, Gisela; Gálvez, Pablo; Araya, Ignacio; Yanine, Nicolás; Carrasco-Labra, Alonso; Oliva, Patricio; Brignardello-Petersen, Romina; Villanueva, Julio

    2012-09-01

      To provide the users with information on the current best practices for managing the oral health care of people living with EB.   A systematic literature search, in which the main topic is dental care in patients with Epidermolysis Bullosa, was performed. Consulted sources, ranging from 1970 to 2010, included MEDLINE, EMBASE, CINAHL, The Cochrane Library, DARE, and the Cochrane controlled trials register (CENTRAL). In order to formulate the recommendations of the selected studies the SIGN system was used. The first draft was analysed and discussed by clinical experts, methodologists and patients representatives on a two days consensus meeting. The resulting document went through an external review process by a panel of experts, other health care professionals, patient representatives and lay reviewers. The final document was piloted in three different centres in United Kingdom, Czech Republic and Argentina.   The guideline is composed of 93 recommendations divided into 3 main areas: 1) Oral Care--access issues, early referral, preventative strategies, management of microstomia, prescriptions and review appointments 2) Dental treatment: general treatment modifications, radiographs, restorations, endodontics, oral rehabilitation, periodontal treatment, oral surgery and orthodontics, and 3) Anaesthetic management of dental treatment.   A preventive protocol is today's dental management approach of choice. © 2012 The Authors. International Journal of Paediatric Dentistry © 2012 BSPD, IAPD and Blackwell Publishing Ltd.

  9. Clinical application of amniotic membranes on a patient with epidermolysis bullosa.

    PubMed

    Martínez Pardo, M E; Reyes Frías, M L; Ramos Durón, L E; Gutiérrez Salgado, E; Gómez, J C; Marín, M A; Luna Zaragoza, D

    1999-01-01

    The case of a patient with dystrophic epidermolysis bullosa treated with radiosterilised amniotic membranes is presented. The disorder is a congenital disease characterised by a poor desmosomal junction in the keratinocyte membrane. After proper donor screening, amnios were collected at Hospital Central Sur de Alta Especialidad (HCSAE), PEMEX and microbiological analysis was performed at Universidad Nacional Autónoma de México, FQUNAM, (Biology Dept. of the Chemistry Faculty, National Autonomous University of Mexico), before and after radiation sterilisation. Processing, packaging and sterilisation were performed at Instituto Nacional de Investigaciones Nucleares, ININ, (National Nuclear Research Institute). The patient, a ten-year-old boy with severe malnutrition, extensive loss of skin and pseudomonad infection in the whole body, was treated with gentle debridement in a Hubbard bath. Later amnion application was performed with sterilised amnios by using two different processes, in one of which the amnion was sterilised with paracetic acid, preserved in glycerol, kindly donated by the German Institute for Tissue and Cell Replacement and applied by Dr. Johannes C. Bruck, IAEA visiting expert, and the other amnion was processed at ININ: air dried and sterilised by gamma radiation at dose of 30 kGy. After spontaneous epithelisation was successfully promoted for seven days, the pain was alleviated and mobility was improved in a few hours and the patient's general condition was so improved that in a month he was discharged. Unfortunately, because this disease is revertive and has malignant degeneration, the prognosis is not good.

  10. Transcriptome and ultrastructural changes in dystrophic Epidermolysis bullosa resemble skin aging

    PubMed Central

    Trost, Andrea; Weber, Manuela; Klausegger, Alfred; Gruber, Christina; Bruckner, Daniela; Reitsamer, Herbert A.; Bauer, Johann W.; Breitenbach, Michael

    2015-01-01

    The aging process of skin has been investigated recently with respect to mitochondrial function and oxidative stress. We have here observed striking phenotypic and clinical similarity between skin aging and recessive dystrophic Epidermolysis bullosa (RDEB), which is caused by recessive mutations in the gene coding for collagen VII, COL7A1. Ultrastructural changes, defects in wound healing, and inflammation markers are in part shared with aged skin. We have here compared the skin transcriptomes of young adults suffering from RDEB with that of sex‐ and age‐matched healthy probands. In parallel we have compared the skin transcriptome of healthy young adults with that of elderly healthy donors. Quite surprisingly, there was a large overlap of the two gene lists that concerned a limited number of functional protein families. Most prominent among the proteins found are a number of proteins of the cornified envelope or proteins mechanistically involved in cornification and other skin proteins. Further, the overlap list contains a large number of genes with a known role in inflammation. We are documenting some of the most prominent ultrastructural and protein changes by immunofluorescence analysis of skin sections from patients, old individuals, and healthy controls. PMID:26143532

  11. Er:YAG Laser Dental Treatment of Patients Affected by Epidermolysis Bullosa

    PubMed Central

    Galeotti, Angela; D'Antò, Vincenzo; Gentile, Tina; Giancristoforo, Simona; Romeo, Umberto

    2014-01-01

    Aim. The purpose of this study was to evaluate the efficacy of Er:YAG laser used for treating hard dental tissue in patients with epidermolysis bullosa (EB). Methods. We report two cases of EB in which an Er:YAG laser was used for conservative treatments. In the first case, the Er:YAG laser (2,940 μm, 265 mJ, 25 Hz) was used to treat caries on a deciduous maxillary canine in an 8-year-old male patient affected by dystrophic EB. In the second case, we treated a 26-year-old female patient, affected by junctional EB, with generalized enamel hypoplasia, and an Er:YAG laser (2,940 μm, 265 mJ, 25 Hz) was used to remove the damaged enamel on maxillary incisors. Results. The use of the Er:YAG laser, with the appropriate energy, was effective in the selective removal of carious tissue and enamel hypoplasia. During dental treatment with the Er:YAG laser, patients required only a few interruptions due to the absence of pain, vibration, and noise. Conclusions. Laser treatment of hard dental tissues is a valuable choice for patients affected by EB since it is less invasive compared to conventional treatment, resulting in improved patient compliance. PMID:25431688

  12. Evaluation of internal consistency of the epidermolysis bullosa oropharyngeal severity score (EBOS).

    PubMed

    Fortuna, Giulio; Aria, Massimo; Cepeda-Valdes, Rodrigo; Salas-Alanís, Julio Cesar

    2015-02-01

    To evaluate the internal consistency of the epidermolysis bullosa oropharyngeal severity score (EBOS). Data from 92 patients of varying EB types/sub-types already described in a previous multi-center study were re-analyzed via the coefficient Cronbach's α (CR-α). Additionally, the corrected item total correlation between each item and the items' overall score with Pearson's product-moment correlation (ρ) was calculated. The alpha coefficient for the mean total score of 17 items is 0.941. The inter-observer reliability for disease severity score was excellent for oral medicine specialist (α = 0.924) and dermatologist (α = 0.916) and the intra-observer reliability was good at Time 1 (α = 0.895) and Time 2 (α = 0.897). The analysis of CR-α per single item revealed that alpha was greater than 0.904 for disease activity and 0.743 for structural damage, after the elimination of four items for oral medicine specialist and greater than 0.898 for disease activity and 0.769 for structural damage after the elimination of five items for dermatologist. Similarly the analysis of the corrected items-EBOS correlation showed that the same items do not correlate very well (ρ < 0.4) with the overall EBOS. The EBOS turned out to have a strong and reliable internal consistency, as the majority of the EBOS' items were consistent with each other.

  13. Using Urgotul dressing for the management of epidermolysis bullosa skin lesions.

    PubMed

    Blanchet-Bardon, C; Bohbot, S

    2005-11-01

    To evaluate the acceptability, tolerance and efficacy of Urgotul wound dressing in the management of epidermolysis bullosa (EB) skin lesions. This was an open-label uncontrolled clinical trial involving 20 patients (I I adults and nine children) with EB simplex or dystrophic EB. Patients were selected from the register of EB patients at the investigating centre and included if they presented with at least one skin lesion requiring management with a non-adherent wound dressing. Lesions were treated with the study dressing for a maximum of four weeks. All dressing changes, wound parameters, pain and effect on quality of life were recorded. All patients completed the trial. Nineteen out of 20 wounds healed within 8.7 +/- 8.5 days. Overall, 11 patients (55%) considered that their quality of life had improved following use of the dressing, which was also reported to be pain free and 'very easy' or 'easy' to remove at most dressing changes. Nineteen out of 20 patients stated that they would use the study dressing to manage their lesions in future. This study confirmed the very good acceptability and efficacy of Urgotul in the treatment of skin lesions in patients with EB.

  14. The main problems of parents of a child with epidermolysis bullosa.

    PubMed

    van Scheppingen, Corinne; Lettinga, Ant T; Duipmans, José C; Maathuis, Karel G B; Jonkman, Marcel F

    2008-04-01

    Epidermolysis Bullosa (EB) is a rare genetic blistering-skin disorder with varying degrees of severity, ranging from mild forms to severe forms, with chronic progression. The aim of this study was to identify and specify the problems of parents of a child with EB. Qualitative research methodology was used, comprising a series of semistructured interviews with eleven families. The key problems of parents were broken down into three themes, related to the child, the family, and the care providers. These themes comprised nine categories, including (1) the child being different, (2) the child suffering pain, (3) feelings of uncertainty, (4) restrictions on employment and leisure time, (5) difficulties in organization of care, (6) never being off-duty, (7) family problems, (8) ignorance and lack of skills of care providers, and (9) resistance to difficult care. Despite the great variance in clinical pictures of the different (sub)types of EB, the main problems parents experienced appear quite similar. However, the problems did appear to differ in extensiveness, intensity, and gravity.

  15. Apocytolysis, a proposed mechanism of blister formation in epidermolysis bullosa simplex.

    PubMed

    El-Hawary, Marwa S; Abdel-Halim, Mona R E; Sayed, Safinaz S; Abdelkader, Heba A

    2015-05-01

    Epidermolysis bullosa simplex (EBS) is caused by keratin 5 and 14 mutations. In vitro studies revealed that susceptibility to caspase 8-mediated apoptosis is increased in keratin 14 mutated keratinocytes. We aimed to investigate the role of apoptotic/inflammatory pathways in the pathogenesis of EBS by studying the expression of caspase 8 in lesional and non-lesional skin compared to controls. Ten EBS patients proved by electron microscopy and five age and sex matched healthy volunteers were the subjects of this case control study. Caspase 8 expression was studied by immunohistochemistry. Caspase 8 expression in lesional and non-lesional skin was significantly higher than in controls (p < 0.01 and p = 0.013, respectively) with no significant difference between lesional and non-lesional skin. Lesional skin had significantly higher density of dermal infiltrate (p = 0.02). Caspase 8 expression in lesional skin was significantly correlated with the extent of the disease, rate of blistering, and density of dermal infiltrate (r = 0.835; p = 0.003, r = 0.889; p = 0.001 and r = 0.776; p = 0.008 respectively). Caspase 8-mediated apoptosis is an integral component of an orchestra of events conducted by keratin mutation. Apo-cytolysis is proposed to better describe the mechanism of blistering in EBS. The small number of cases is a limitation.

  16. Epidermolysis bullosa simplex in sibling Eurasier dogs is caused by a PLEC non-sense variant

    PubMed Central

    Mauldin, Elizabeth A.; Wang, Ping; Olivry, Thierry; Henthorn, Paula S.; Casal, Margret L.

    2017-01-01

    Background Plectin, a large linker protein found in many tissues, acts to connect components of the cytoskeleton to each other. In the epidermis, plectin binds keratin intermediate filaments to hemidesmosomes. A deficiency of plectin in the skin leads to blister formation in the basal layer and the disease epidermolysis bullosa simplex (EBS). Hypothesis/Objectives To describe a novel blistering disease that arose spontaneously in a litter of puppies. Animals Two female and one male 20-day-old Eurasier puppies, from a litter of six, were presented for evaluation of failure to thrive and then euthanized due to poor prognosis. The puppies had ulcers on the lips, tongue, nasal planum, paw pads and abdomen. Results – Immunolabelling on frozen skin for basement membrane proteins revealed patchy and weak to absent staining for plectin as compared with strong linear staining in normal dogs. Ultrastructurally, hemidesmosomes were irregularly shaped and had loss of distinction between inner and outer plaques. Pedigree analysis supported an autosomal recessive mode of inheritance. A premature stop codon was discovered in exon 27 of PLEC that resulted in the production of a severely truncated protein. Conclusion The study describes the first documented spontaneous EBS associated with a PLEC variant in domestic animals. PMID:27878870

  17. Epidermolysis bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene.

    PubMed

    Murgiano, Leonardo; Wiedemar, Natalie; Jagannathan, Vidhya; Isling, Louise K; Drögemüller, Cord; Agerholm, Jørgen S

    2015-02-07

    Heritable forms of epidermolysis bullosa (EB) constitute a heterogeneous group of skin disorders of genetic aetiology that are characterised by skin and mucous membrane blistering and ulceration in response to even minor trauma. Here we report the occurrence of EB in three Danish Hereford cattle from one herd. Two of the animals were necropsied and showed oral mucosal blistering, skin ulcerations and partly loss of horn on the claws. Lesions were histologically characterized by subepidermal blisters and ulcers. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We performed whole genome sequencing of one affected calf and searched all coding DNA variants. Thereby, we detected a homozygous 2.4 kb deletion encompassing the first exon of the LAMC2 gene, encoding for laminin gamma 2 protein. This loss of function mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. The deletion co-segregates with the EB phenotype in the family and absent in normal cattle of various breeds. Verifying the homozygous private variants present in candidate genes allowed us to quickly identify the causative mutation and contribute to the final diagnosis of junctional EB in Hereford cattle. Our investigation confirms the known role of laminin gamma 2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare diseases in livestock.

  18. Corrective transduction of human epidermal stem cells in laminin-5-dependent junctional epidermolysis bullosa.

    PubMed

    Dellambra, E; Vailly, J; Pellegrini, G; Bondanza, S; Golisano, O; Macchia, C; Zambruno, G; Meneguzzi, G; De Luca, M

    1998-06-10

    Laminin-5 is composed of three distinct polypeptides, alpha3, beta3, and gamma2, which are encoded by three different genes, LAMA3, LAMB3, and LAMC2, respectively. We have isolated epidermal keratinocytes from a patient presenting with a lethal form of junctional epidermolysis bullosa characterized by a homozygous mutation of the LAMB3 gene, which led to complete absence of the beta3 polypeptide. In vitro, beta3-null keratinocytes were unable to synthesize laminin-5 and to assemble hemidesmosomes, maintained the impairment of their adhesive properties, and displayed a decrease of their colony-forming ability. A retroviral construct expressing a human beta3 cDNA was used to transduce primary beta3-null keratinocytes. Clonogenic beta3-null keratinocytes were transduced with an efficiency of 100%. Beta3-transduced keratinocytes were able to synthesize and secrete mature heterotrimeric laminin-5. Gene correction fully restored the keratinocyte adhesion machinery, including the capacity of proper hemidesmosomal assembly, and prevented the loss of the colony-forming ability, suggesting a direct link between adhesion to laminin-5 and keratinocyte proliferative capacity. Clonal analysis demonstrated that holoclones expressed the transgene permanently, suggesting stable correction of epidermal stem cells. Because cultured keratinocytes are used routinely to make autologous grafts for patients suffering from large skin or mucosal defects, the full phenotypic reversion of primary human epidermal stem cells defective for a structural protein opens new perspectives in the long-term treatment of genodermatoses.

  19. T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

    PubMed Central

    Bieber, Katja; Witte, Mareike; Sun, Shijie; Hundt, Jennifer E.; Kalies, Kathrin; Dräger, Sören; Kasprick, Anika; Twelkmeyer, Trix; Manz, Rudolf A.; König, Peter; Köhl, Jörg; Zillikens, Detlef; Ludwig, Ralf J.

    2016-01-01

    T cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organ-specific autoimmune disease, namely epidermolysis bullosa acquisita (EBA) – characterized and caused by autoantibodies targeting type VII collagen. Specifically, we show that immune complex (IC)-induced inflammation depends on the presence of T cells – a process facilitated by T cell receptor (TCR)γδ and NKT cells. Because tissue damage in IC-induced inflammation is neutrophil-dependent, we further analyze the interplay between T cells and neutrophils in an experimental model of EBA. We demonstrate that T cells not only enhance neutrophil recruitment into the site of inflammation but also interact with neutrophils in lymphatic organs. Collectively, this study shows that T cells amplify the effector phase of antibody-induced tissue inflammation. PMID:27917914

  20. Clinical comparison of the Bactec Mycosis IC/F, BacT/Alert FA, and BacT/Alert FN blood culture vials for the detection of candidemia.

    PubMed

    Ericson, Eva-Lena; Klingspor, Lena; Ullberg, Måns; Ozenci, Volkan

    2012-06-01

    The present study analyzed the performance of Bactec Mycosis IC/F, BacT/Alert FA, and BacT/Alert FN vials in detection and time to detection (TTD) of Candida spp. in 179 simultaneous blood cultures. The Mycosis IC/F, BacT/Alert FA, and BacT/Alert FN vials could detect Candida spp. in 144 (80.45%) of 179, 149 (83.24%) of 179, and 8 (4.47%) of 179 samples, respectively. With the presence of antifungal therapy, the numbers of positive vials were higher in BacT/Alert FA compared to Mycosis IC/F, 87/99 versus 73/99, respectively (P < 0.05). TTD (SD) for C. albicans was shorter in Mycosis IC/F than in BacT/Alert FA vials without antifungal therapy, 20.89 (9.33) versus 28.26 (9.77), respectively (P < 0.01). The detection of Candida spp., with concomitant bacteremia, was higher in Mycosis IC/F than in BacT/Alert FA vials, 28/30 and 19/30, respectively (P = 0.01). The present data show that the use of Bactec Mycosis IC/F together with BacT/Alert FA vials might improve the detection of Candida spp.

  1. Combining GWAS and RNA-Seq Approaches for Detection of the Causal Mutation for Hereditary Junctional Epidermolysis Bullosa in Sheep.

    PubMed

    Suárez-Vega, Aroa; Gutiérrez-Gil, Beatriz; Benavides, Julio; Perez, Valentín; Tosser-Klopp, Gwenola; Klopp, Christophe; Keennel, Stephen J; Arranz, Juan José

    2015-01-01

    In this study, we demonstrate the use of a genome-wide association mapping together with RNA-seq in a reduced number of samples, as an efficient approach to detect the causal mutation for a Mendelian disease. Junctional epidermolysis bullosa is a recessive genodermatosis that manifests with neonatal mechanical fragility of the skin, blistering confined to the lamina lucida of the basement membrane and severe alteration of the hemidesmosomal junctions. In Spanish Churra sheep, junctional epidermolysis bullosa (JEB) has been detected in two commercial flocks. The JEB locus was mapped to Ovis aries chromosome 11 by GWAS and subsequently fine-mapped to an 868-kb homozygous segment using the identical-by-descent method. The ITGB4, which is located within this region, was identified as the best positional and functional candidate gene. The RNA-seq variant analysis enabled us to discover a 4-bp deletion within exon 33 of the ITGB4 gene (c.4412_4415del). The c.4412_4415del mutation causes a frameshift resulting in a premature stop codon at position 1472 of the integrin β4 protein. A functional analysis of this deletion revealed decreased levels of mRNA in JEB skin samples and the absence of integrin β4 labeling in immunohistochemical assays. Genotyping of c.4412_4415del showed perfect concordance with the recessive mode of the disease phenotype. Selection against this causal mutation will now be used to solve the problem of JEB in flocks of Churra sheep. Furthermore, the identification of the ITGB4 mutation means that affected sheep can be used as a large mammal animal model for the human form of epidermolysis bullosa with aplasia cutis. Our approach evidences that RNA-seq offers cost-effective alternative to identify variants in the species in which high resolution exome-sequencing is not straightforward.

  2. Combining GWAS and RNA-Seq Approaches for Detection of the Causal Mutation for Hereditary Junctional Epidermolysis Bullosa in Sheep

    PubMed Central

    Suárez-Vega, Aroa; Gutiérrez-Gil, Beatriz; Benavides, Julio; Perez, Valentín; Tosser-Klopp, Gwenola; Klopp, Christophe; Keennel, Stephen J.; Arranz, Juan José

    2015-01-01

    In this study, we demonstrate the use of a genome-wide association mapping together with RNA-seq in a reduced number of samples, as an efficient approach to detect the causal mutation for a Mendelian disease. Junctional epidermolysis bullosa is a recessive genodermatosis that manifests with neonatal mechanical fragility of the skin, blistering confined to the lamina lucida of the basement membrane and severe alteration of the hemidesmosomal junctions. In Spanish Churra sheep, junctional epidermolysis bullosa (JEB) has been detected in two commercial flocks. The JEB locus was mapped to Ovis aries chromosome 11 by GWAS and subsequently fine-mapped to an 868-kb homozygous segment using the identical-by-descent method. The ITGB4, which is located within this region, was identified as the best positional and functional candidate gene. The RNA-seq variant analysis enabled us to discover a 4-bp deletion within exon 33 of the ITGB4 gene (c.4412_4415del). The c.4412_4415del mutation causes a frameshift resulting in a premature stop codon at position 1472 of the integrin β4 protein. A functional analysis of this deletion revealed decreased levels of mRNA in JEB skin samples and the absence of integrin β4 labeling in immunohistochemical assays. Genotyping of c.4412_4415del showed perfect concordance with the recessive mode of the disease phenotype. Selection against this causal mutation will now be used to solve the problem of JEB in flocks of Churra sheep. Furthermore, the identification of the ITGB4 mutation means that affected sheep can be used as a large mammal animal model for the human form of epidermolysis bullosa with aplasia cutis. Our approach evidences that RNA-seq offers cost-effective alternative to identify variants in the species in which high resolution exome-sequencing is not straightforward. PMID:25955497

  3. [Prehospital emergency setting caused by hemorrhagic oropharyngeal bullae in a child with dystrophic epidermolysis bullosa Hallopeau-Siemens].

    PubMed

    Ochsenfahrt, C; Maier, B; Konrad, F

    2004-01-01

    Two painful large hemorrhagic bullae developed within minutes of each other in a four-month-old infant with autosomal recessive inherited epidermolysis bullosa dystrophica Hallopeau-Siemens. There was no significant impairment of spontaneous respiration. The emergency physician sedated the infant with midazolam administered by the nasal route. A community pediatrician called for assistance opened a bulla, which impressively improved the symptoms and avoided the necessity of an admission to hospital. The presented case demonstrates the importance of exchange of information within the group of emergency physicians regarding rare diseases not only in rural areas. In our opinion its also helpful to involve colleagues in private practice into the emergency system.

  4. In vitro response of cutaneous mycosis fungal agents to the most widely used systemic antifungals in dermatology.

    PubMed

    Almeida, Lívia Maria Martins de; Souza, Eliane Alves de Freitas; Bianchin, Débora Bertoluzzi; Svidzinski, Terezinha Inez Estivalet

    2009-07-01

    The high frequency of cutaneous mycosis justify the need to evaluate the possible contribution of in vitro profile of susceptibility to antifungal agents. To evaluate whether there is variability in in vitro susceptibility by filamentous fungi, previously isolated from cutaneous mycosis, to fluconazole, ketoconazole, itraconazole and terbinafine. Fungi were isolated and identified by classical methods and the antifungal susceptibility test was performed using the method of broth microdilution, according to a protocol recommended by the Clinical Laboratory Standards Institute (CLSI), through M38-A document. Amongst the 80 filamentous fungi identified, Trichophyton genus represented 81%. The four examined drugs showed great variation for Trichophyton spp and Microsporum spp. Fusarium spp was resistant to all tested drugs. Terbinafine was the most effective drug against the majority of the isolated fungi. There was great variability in response profiles to the tested antifungals. The definition of a reference test method will offer higher objectivity for physicians to choose the appropriate therapy.

  5. Gelling Your Dermatology Nursing Practice

    PubMed Central

    McCann, Sue A.; Chase, Allister Benjamin; Tawa, Marianne C.

    2016-01-01

    ABSTRACT Mycosis fungoides is the most common form of cutaneous T-cell lymphoma. Stage IA and IB mycosis fungoides cutaneous T-cell lymphoma can be effectively controlled by skin-directed therapies such as the mechlorethamine gel approved by the Food and Drug Administration. Dermatology nurses play a key role in promoting good patient compliance through patient education about mycosis fungoides cutaneous T-cell lymphoma disease, proper administration of mechlorethamine gel, and connecting patients with patient assistance programs or other supportive services. This article provides the dermatology nurse with a background about early-stage mycosis fungoides cutaneous T-cell lymphoma, skin-directed treatment options, questions that a patient may ask about mycosis fungoides cutaneous T-cell lymphoma and mechlorethamine gel, and patient education tools such as questions dermatology nurses may ask of their patients and a patient handout outlining mechlorethamine gel administration.

  6. Prenatal diagnosis for epidermolysis bullosa: a study of 144 consecutive pregnancies at risk.

    PubMed

    Pfendner, Ellen G; Nakano, Aoi; Pulkkinen, Leena; Christiano, Angela M; Uitto, Jouni

    2003-06-01

    Epidermolysis bullosa (EB) is a group of inherited disorders characterized by increased skin fragility, resulting in blisters and erosions after minor trauma. Mutations in 10 structural genes expressed in the cutaneous basement membrane zone have been reported. The DebRA Molecular Diagnostics Laboratory at Jefferson Medical College has performed 144 DNA-based prenatal diagnoses since 1993 in families at risk for recurrence of the most severe forms of EB, including the recessive dystrophic EB (RDEB), junctional EB (JEB), EB with pyloric atresia (EB-PA), and EB simplex (EBS). A mutation-detection strategy using either conformation-sensitive gel electrophoresis (CSGE) or denaturing high-performance liquid chromatography (dHPLC) scanning analysis, followed by nucleotide sequencing, was applied to most cases with DEB and to all JEB, EB-PA, and EBS families. For some RDEB families, linkage analysis was performed, either alone when the inheritance pattern was clear or in combination with one mutation. Among the 144 prenatal diagnoses, 63 were for RDEB, 69 for JEB, 6 for EB-PA, and 6 for EBS. Twenty-eight normal, 73 heterozygous carrier, and 28 affected RDEB, JEB, and EB-PA pregnancies were reported in these recessively inherited diseases. Two affected and four normal pregnancies were predicted in dominantly inherited EBS. Among the 144 pregnancies, 9 were terminated without confirmation, 13 cases were lost to follow-up, and 6 pregnancies are ongoing. There were 6 families with inconclusive results due either to recombination events between flanking markers, absence of informative markers for one allele, or lack of sample from the previously affected child. There were three discordant results, one that was explained by maternal contamination of the chorionic villus sample and two that were unresolved. Overall, the availability, relative ease, and over 98% success rate make molecular DNA-based prenatal diagnosis a viable option for EB families at risk.

  7. [Nursing Experience With Providing Wound Care for a Newborn With Epidermolysis Bullosa].

    PubMed

    Hsu, Hsiao-Hui; Zheng, Xin-Yi; Hsu, Mei-Yu

    2015-12-01

    Epidermolysis bullosa (EB) is a rare hereditary, chromosomal disease of the skin. Life-threatening septicemia may result if appropriate care is not provided to alleviate the extensive skin irritation that is the main symptom of this disease. This case report describes the experience of the author in nursing a wound area on a newborn that was suspected of being caused by EB. This wound area comprised blisters and peeling skin that covered 30% of the entire skin area of the infant. A holistic assessment conducted from December 1st, 2013 to January 7th, 2014 revealed that this large of an area of damage to the skin and mucosa considerably complicated the task of wound care and caused severe pain to the infant. In response to the special needs of this case, our medical team conducted a literature review of wound care for this rare disease. Based on the suggestions of previous empirical studies, nursing measures for the skin, mucosa, and wounds of the newborn were then administered through inter-team cooperation. These actions effectively reduced the pain, controlled the infection, and accelerated wound healing. In addition, progressive contact was used to guide the primary caregivers of the newborn, which alleviated their physical and psychological stresses effectively. The caregivers were educated systematically on wound care and guided to learn techniques for nursing and dressing wounds. Thus, these caregivers were better prepared to continue providing wound care at home. We suggest that healthcare professionals reference empirical studies when providing care to EB newborns during the acute-care period and provide wound care and supportive therapies to control the occurrence of complications using a multidisciplinary team-care model. In addition, social resources should be used effectively in nursing care plans to mitigate the effect of this rare disease on families.

  8. Development, reliability, and validity of a novel Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI).

    PubMed

    Loh, Clement C H; Kim, Jaehwan; Su, John C; Daniel, Benjamin S; Venugopal, Supriya S; Rhodes, Lesley M; Intong, Lizbeth R A; Law, Matthew G; Murrell, Dedee F

    2014-01-01

    There is a lack of validated standardized outcome measures for epidermolysis bullosa (EB) that can separate activity from damage. We sought to develop and validate an instrument for inherited EB of all ages and subtypes, the EB Disease Activity and Scarring Index (EBDASI), which scores activity responsive to therapy separately from scarring. The EBDASI was validated by comparing its reliability and validity against the Birmingham EB Severity (BEBS) score (partially validated with activity mixed with scarring), using the Physician Global Assessment (PGA) scale as a reference measurement. Sixteen patients with EB (7 EB simplex, 5 dominant dystrophic EB [DDEB], 2 junctional EB, and 2 recessive dystrophic EB) were assessed by 5 EB experts using the EBDASI, BEBS, and PGA, and data from 9 additional patients assessed on an ad hoc basis during routine patient clinic were also included. For interrater reliability, the overall total score intraclass correlation coefficients (95% confidence intervals) were: EBDASI 0.964 (0.929-0.986), BEBS 0.852 (0.730-0.937), and PGA 0.873 (0.765-0.946). For intrarater reliability, the intraclass correlation coefficients were: EBDASI 0.994 (0.976-0.998), BEBS 0.926 (0.748-0.981), and PGA 0.932 (0.764-0.982). The EBDASI had a higher correlation with PGA (ρ = 0.871) than BEBS with PGA (ρ = 0.852). Intraclass correlation coefficients scatterplots showed the EBDASI was better at distinguishing milder forms of EB, with better correlations at higher severity scores than the BEBS. A limited number of patients were recruited for this study. An independent study will be required to demonstrate the responsiveness of the EBDASI. The EBDASI demonstrated excellent reliability and validity, as compared with 2 other outcome measures. Copyright © 2013 American Academy of Dermatology, Inc. All rights reserved.

  9. [Hereditary epidermolysis bullosa: French national guidelines (PNDS) for diagnosis and treatment].

    PubMed

    Chiaverini, C; Bourrat, E; Mazereeuw-Hautier, J; Hadj-Rabia, S; Bodemer, C; Lacour, J-P

    2017-01-01

    Hereditary epidermolysis bullosa (EB) is a heterogeneous group of rare genetic diseases characterized by fragile skin and/or mucous membrane, and it may be either local or generalized. It is caused by mutations in genes encoding different proteins involved mainly in the structure and function of the dermal-epidermal junction. Nineteen genes have so far been identified. They are classified by level of skin cleavage (from top to bottom) into four groups: EB simplex, junctional EB, dystrophic EB and Kindler syndrome. Clinically suspected diagnosis is confirmed by immunohistochemical examination of a skin biopsy at specialized centres in order to determine the level of cleavage and the deficient protein. This first step may be followed by genetic analysis. The severity of the disease is highly variable, ranging from localized forms with little effect on quality of life to rapidly lethal forms. In generalized severe forms, the extent and chronicity of lesions, as well as mucosal involvement, can lead to systemic complications: malnutrition, pain, joint contractures, chronic inflammation, amyloidosis, cutaneous squamous cell carcinoma. Some specific forms are associated with other cutaneous signs (nail involvement, alopecia, hyperpigmentation, palmoplantar keratoderma) or extracutaneous involvement (muscular dystrophy or pyloric atresia). No curative treatment of EB is available today. EB requires multidisciplinary medical care, nursing, psychological and social management. This is best provided by a specialized network, involving reference centres, centres of expertise and daily caregivers. The goal of treatment is the prevention and treatment of lesions with specific non-adherent dressings and the prevention, detection and treatment of complications. It is essential not to traumatize the skin (bandaging, friction, etc.). Protein, gene or cell replacement therapy, and allogeneic bone marrow, cord blood or pluripotent stem-cell transplantation are currently being

  10. CRISPR/Cas9-based genetic correction for recessive dystrophic epidermolysis bullosa

    PubMed Central

    McElroy, Amber N; Twaroski, Kirk; Lonetree, Cara-lin; DeFeo, Anthony P; Xia, Lily; Eide, Cindy; Lees, Christopher J; McElmurry, Ron T; Riddle, Megan J; Kim, Chong Jai; Patel, Dharmeshkumar D; Blazar, Bruce R; Tolar, Jakub

    2017-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is a severe disorder caused by mutations to the COL7A1 gene that deactivate production of a structural protein essential for skin integrity. Haematopoietic cell transplantation can ameliorate some of the symptoms; however, significant side effects from the allogeneic transplant procedure can occur and unresponsive areas of blistering persist. Therefore, we employed genome editing in patient-derived cells to create an autologous platform for multilineage engineering of therapeutic cell types. The clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system facilitated correction of an RDEB-causing COL7A1 mutation in primary fibroblasts that were then used to derive induced pluripotent stem cells (iPSCs). The resulting iPSCs were subsequently re-differentiated into keratinocytes, mesenchymal stem cells (MSCs) and haematopoietic progenitor cells using defined differentiation strategies. Gene-corrected keratinocytes exhibited characteristic epithelial morphology and expressed keratinocyte-specific genes and transcription factors. iPSC-derived MSCs exhibited a spindle morphology and expression of CD73, CD90 and CD105 with the ability to undergo adipogenic, chondrogenic and osteogenic differentiation in vitro in a manner indistinguishable from bone marrow-derived MSCs. Finally, we used a vascular induction strategy to generate potent definitive haematopoietic progenitors capable of multilineage differentiation in methylcellulose-based assays. In totality, we have shown that CRISPR/Cas9 is an adaptable gene-editing strategy that can be coupled with iPSC technology to produce multiple gene-corrected autologous cell types with therapeutic potential for RDEB. PMID:28250968

  11. Quality of Life and Economic Burden in Recessive Dystrophic Epidermolysis Bullosa

    PubMed Central

    Jeon, In Kyung; On, Hye Rang

    2016-01-01

    Background Patients with recessive dystrophic epidermolysis bullosa (RDEB) exhibit blisters and erosions since birth, causing pain, pruritus and various complications. RDEB affects quality of life (QoL) in physical, emotional and social aspects. Furthermore, interminable dressing changes and supportive therapies impose a significant economic burden on the patient's family. Objective We assessed the QoL and economic burden in patients with RDEB. Methods Sixteen patients with RDEB were surveyed to assess the QoL and economic burden. Patients answered questionnaires consisting of a visual analogue scale (VAS) on pain and pruritus, Skindex-29, Quality of Life in EB questionnaire (QOLEB), and the economic burden due to EB. Results Thirteen patients with RDEB completed the questionnaire. Female patients presented higher VAS, QOLEB and total Skindex-29 scores than male patients. Patients with RDEB showed severe levels of pruritus, which was more intolerable than pain. Mean VAS score on pain in RDEB was higher than in oral lichen planus and post-herpetic neuralgia. VAS score on pruritus was similar to those in chronic urticaria, atopic dermatitis, and prurigo nodularis. Compared with other dermatologic conditions, patients with RDEB were profoundly affected in all three scales of skindex-29. Mean "medical cost" in a month was $257.54 (USD) (±169.39) and mean "dressing cost" was $358.41 (USD) (±312.55), which was negatively related to patient age. Conclusion RDEB had a profound impact on QoL and economic burden. Compared with other dermatologic diseases, RDEB showed severe symptoms and QoL was seriously impaired. Most patients sustained economic burdens, especially on preparing dressing materials. Younger patients experienced more economic burdens. PMID:26848213

  12. A novel deletion and two recurrent substitutions on type VII collagen gene in seven Iranian patients with epidermolysis bullosa.

    PubMed

    Hamidi, Armita Kakavand; Moghaddam, Mohammad; Hatamnejadian, Nasim; Ebrahimi, Ahmad

    2016-08-01

    Epidermolysis bullosa is one of the most important series of mechano-bullous heritable skin disorders which is categorized into four major types according to the layer that bullae forms within basement membrane zone. In dystrophic form of the disease, blisters are made in the sublamina densa zone, at the level of type VII collagen protein which produce anchoring fibrils. Type VII collagen gene is the only responsible gene for this form. The aim of this study was to survey causative mutations of type VII collagen gene among Iranian patients with epidermolysis bullosa. For this purpose, exons 73-75 were investigated by polymerase chain reaction followed by direct sequencing. In current study, we found three different point mutations in type VII collagen alleles in 7 out of 50 patients. Four patients were homozygous for a new deletion which resulted in frame shift (p.Pro2089fs). Two patients were homozygous for a recurrent glycine substitution (p.G2031S) and one patient was detected with an allele carrying a substitution (p.R2069C). The results emphasized heterogeneity in the type VII collagen gene and will provide a sign for early diagnosis and future study of the disease pathogenesis.

  13. A stop-gain in the laminin, alpha 3 gene causes recessive junctional epidermolysis bullosa in Belgian Blue cattle.

    PubMed

    Sartelet, Arnaud; Harland, Chad; Tamma, Nico; Karim, Latifa; Bayrou, Calixte; Li, Wanbo; Ahariz, Naima; Coppieters, Wouter; Georges, Michel; Charlier, Carole

    2015-10-01

    Four newborn purebred Belgian Blue calves presenting a severe form of epidermolysis bullosa were recently referred to our heredo-surveillance platform. SNP array genotyping followed by autozygosity mapping located the causative gene in a 8.3-Mb interval on bovine chromosome 24. Combining information from (i) whole-genome sequencing of an affected calf, (ii) transcriptomic data from a panel of tissues and (iii) a list of functionally ranked positional candidates pinpointed a private G to A nucleotide substitution in the LAMA3 gene that creates a premature stop codon (p.Arg2609*) in exon 60, truncating 22% of the corresponding protein. The LAMA3 gene encodes the alpha 3 subunit of the heterotrimeric laminin-332, a key constituent of the lamina lucida that is part of the skin basement membrane connecting epidermis and dermis layers. Homozygous loss-of-function mutations in this gene are known to cause severe junctional epidermolysis bullosa in human, mice, horse, sheep and dog. Overall, our data strongly support the causality of the identified gene and mutation. © 2015 Stichting International Foundation for Animal Genetics.

  14. Feasibility, efficacy, and safety of ultrasound-guided axillary plexus blockade in pediatric patients with epidermolysis bullosa dystrophica.

    PubMed

    van den Heuvel, Ingeborg; Gottschalk, Antje; Langer, Martin; Hahnenkamp, Klaus; Ellger, Björn

    2016-04-01

    In patients suffering from epidermolysis bullosa dystrophica (DEB), the most severe form of epidermolysis bullosa, trauma or friction cause separation of the skin from underlying tissue with consecutive painful blisters, scarifications, contractures, and pseudosyndactyly. To retain functionality of the hands surgical procedures are necessary. Anesthesia is challenging as difficult airways make general anesthesia risky. Regional anesthesia is considered controversial in patients with EB as accidental subcutaneous injections can cause severe blisters. As ultrasound-guided procedures became standard of care this might have changed however. In this case series, we describe feasibility, efficacy, and safety of ultrasound-guided plexus axillaris block in DEB patients undergoing hand surgery. We performed a retrospective analysis of the charts of all children with DEB undergoing hand surgery under plexus axillaris block and sedation between 2009 and 2013 in our institution. Nineteen procedures in nine children were performed. Induction of anesthesia (securing monitoring, sedation, plexus block) took a mean time of 34 min. Perioperative analgesia was adequate in all procedures. No complications such as airway incidents, conversion to general anesthesia, movement during surgery, incomplete block, or formation of new blisters were seen. Ultrasound-guided plexus axillaris block in DEB patients undergoing hand surgery in our institution has been feasible, effective, and safe. © 2016 John Wiley & Sons Ltd.

  15. Case report. Novel and recurrent COL7A1 mutations in Chinese patients with dystrophic epidermolysis bullosa pruriginosa.

    PubMed

    Zhu, K J; Zhu, C Y; Zhou, Y; Fan, Y M

    2014-09-12

    Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of dystrophic epidermolysis bullosa (DEB). This disease is characterized by severe itching, lichenoid nodules or prurigo-like lesions, and linear scarring with a predilection for the extensor limbs. Pathogenic mutations in the type VII collagen alpha 1 (COL7A1) gene have been identified. We analyzed mutations in the COL7A1 gene in a Chinese family including 5 affected individuals with typical DEB-Pr and in a patient previously reported with sporadic DEB-Pr. The entire coding region and exon-intron boundaries of COL7A1 were detected by polymerase chain reaction and direct sequencing. We identified one novel heterozygote mutation (c.6842G>T, p.G2281V) and a second mutation (c.5443G>A, p.G1815R) reported previously in patients with DEB. Our findings contribute to the COL7A1 mutation database and further reveal the genetic and phenotypic heterogeneity of DEB-Pr.

  16. Gene Editing for the Efficient Correction of a Recurrent COL7A1 Mutation in Recessive Dystrophic Epidermolysis Bullosa Keratinocytes.

    PubMed

    Chamorro, Cristina; Mencía, Angeles; Almarza, David; Duarte, Blanca; Büning, Hildegard; Sallach, Jessica; Hausser, Ingrid; Del Río, Marcela; Larcher, Fernando; Murillas, Rodolfo

    2016-04-05

    Clonal gene therapy protocols based on the precise manipulation of epidermal stem cells require highly efficient gene-editing molecular tools. We have combined adeno-associated virus (AAV)-mediated delivery of donor template DNA with transcription activator-like nucleases (TALE) expressed by adenoviral vectors to address the correction of the c.6527insC mutation in the COL7A1 gene, causing recessive dystrophic epidermolysis bullosa in a high percentage of Spanish patients. After transduction with these viral vectors, high frequencies of homology-directed repair were found in clones of keratinocytes derived from a recessive dystrophic epidermolysis bullosa (RDEB) patient homozygous for the c.6527insC mutation. Gene-edited clones recovered the expression of the COL7A1 transcript and collagen VII protein at physiological levels. In addition, treatment of patient keratinocytes with TALE nucleases in the absence of a donor template DNA resulted in nonhomologous end joining (NHEJ)-mediated indel generation in the vicinity of the c.6527insC mutation site in a large proportion of keratinocyte clones. A subset of these indels restored the reading frame of COL7A1 and resulted in abundant, supraphysiological expression levels of mutant or truncated collagen VII protein. Keratinocyte clones corrected both by homology-directed repair (HDR) or NHEJ were used to regenerate skin displaying collagen VII in the dermo-epidermal junction.

  17. A novel deletion and two recurrent substitutions on type VII collagen gene in seven Iranian patients with epidermolysis bullosa

    PubMed Central

    Hamidi, Armita Kakavand; Moghaddam, Mohammad; Hatamnejadian, Nasim; Ebrahimi, Ahmad

    2016-01-01

    Objective(s): Epidermolysis bullosa is one of the most important series of mechano-bullous heritable skin disorders which is categorized into four major types according to the layer that bullae forms within basement membrane zone. In dystrophic form of the disease, blisters are made in the sublamina densa zone, at the level of type VII collagen protein which produce anchoring fibrils. Type VII collagen gene is the only responsible gene for this form. The aim of this study was to survey causative mutations of type VII collagen gene among Iranian patients with epidermolysis bullosa. Materials and Methods: For this purpose, exons 73-75 were investigated by polymerase chain reaction followed by direct sequencing. Results: In current study, we found three different point mutations in type VII collagen alleles in 7 out of 50 patients. Four patients were homozygous for a new deletion which resulted in frame shift (p.Pro2089fs). Two patients were homozygous for a recurrent glycine substitution (p.G2031S) and one patient was detected with an allele carrying a substitution (p.R2069C). Conclusion: The results emphasized heterogeneity in the type VII collagen gene and will provide a sign for early diagnosis and future study of the disease pathogenesis. PMID:27746867

  18. Gene Editing for the Efficient Correction of a Recurrent COL7A1 Mutation in Recessive Dystrophic Epidermolysis Bullosa Keratinocytes

    PubMed Central

    Chamorro, Cristina; Mencía, Angeles; Almarza, David; Duarte, Blanca; Büning, Hildegard; Sallach, Jessica; Hausser, Ingrid; Del Río, Marcela; Larcher, Fernando; Murillas, Rodolfo

    2016-01-01

    Clonal gene therapy protocols based on the precise manipulation of epidermal stem cells require highly efficient gene-editing molecular tools. We have combined adeno-associated virus (AAV)-mediated delivery of donor template DNA with transcription activator-like nucleases (TALE) expressed by adenoviral vectors to address the correction of the c.6527insC mutation in the COL7A1 gene, causing recessive dystrophic epidermolysis bullosa in a high percentage of Spanish patients. After transduction with these viral vectors, high frequencies of homology-directed repair were found in clones of keratinocytes derived from a recessive dystrophic epidermolysis bullosa (RDEB) patient homozygous for the c.6527insC mutation. Gene-edited clones recovered the expression of the COL7A1 transcript and collagen VII protein at physiological levels. In addition, treatment of patient keratinocytes with TALE nucleases in the absence of a donor template DNA resulted in nonhomologous end joining (NHEJ)-mediated indel generation in the vicinity of the c.6527insC mutation site in a large proportion of keratinocyte clones. A subset of these indels restored the reading frame of COL7A1 and resulted in abundant, supraphysiological expression levels of mutant or truncated collagen VII protein. Keratinocyte clones corrected both by homology-directed repair (HDR) or NHEJ were used to regenerate skin displaying collagen VII in the dermo-epidermal junction. PMID:27045209

  19. T cells are required for the production of blister-inducing autoantibodies in experimental epidermolysis bullosa acquisita.

    PubMed

    Sitaru, Ana Gabriela; Sesarman, Alina; Mihai, Sidonia; Chiriac, Mircea T; Zillikens, Detlef; Hultman, Per; Solbach, Werner; Sitaru, Cassian

    2010-02-01

    Epidermolysis bullosa acquisita is a prototypical organ-specific autoimmune disease caused by autoantibodies against type VII collagen of the dermal-epidermal junction. Although mechanisms of autoantibody-induced blister formation were extensively characterized, the initiation of autoantibody production in autoimmune blistering diseases is still poorly defined. In the current study, we addressed the role of T cells for the production of blister-inducing autoantibodies in mice immunized with type VII collagen. To detect autoreactive type VII collagen-specific T cells, lymph node cells from immunized SJL mice were stimulated in vitro with recombinant Ag, and their proliferation was measured by radioactive thymidine incorporation and flow cytometry analysis of CFSE-labeled cells. Interestingly, using synthetic peptides of the immunogen, partly different T and B cell epitopes in mice immunized with type VII collagen were demonstrated. In contrast to wild-type mice, immunization with type VII collagen of SJL athymic nude mice lacking T cells did not induce an autoimmune response and blistering phenotype. Importantly, SJL nude mice repleted with T cells from immunized wild-type mice showed a robust and durable autoantibody production resulting in subepidermal blistering disease in the recipients. Our present results demonstrate that T cells are required for the initiation of autoimmunity against type VII collagen in experimental epidermolysis bullosa acquisita and provide a basis for developing T cell-directed immunomodulatory strategies for this and related autoimmune diseases.

  20. Purified type I collagen wound matrix improves chronic wound healing in patients with recessive dystrophic epidermolysis bullosa.

    PubMed

    Gorell, Emily S; Leung, Thomas H; Khuu, Phuong; Lane, Alfred T

    2015-01-01

    Recessive dystrophic epidermolysis bullosa is a severe genetic blistering skin condition resulting in chronic wounds. Nonhealing wounds were treated over 8 weeks using a reconstituted natural purified type I collagen skin substitute. Chronic wounds were defined as nonhealing wounds present for longer than 6 months. For each patient, two chronic wounds were identified and randomized into a control or treatment group. Both groups received standard-of-care wound dressings. The treatment group received an additional type I collagen skin substitute. Wound size was measured at baseline and weeks 1, 4, and 8. Pain, pruritus, and burning and stinging were assessed. Wound cultures were obtained at baseline and thereafter as was considered clinically relevant. Ten subjects were enrolled; seven completed the study. Six subjects showed a positive response to the type I collagen skin substitute. Three subjects demonstrated full wound reepithelialization. Wounds treated using the collagen skin substitute showed statistically significantly greater improvement. Average scores for pruritus and pain decreased significantly. Reconstituted natural purified type I collagen skin substitutes improved the healing of chronic wounds and may be a valuable addition to the epidermolysis bullosa wound care arsenal. © 2014 Wiley Periodicals, Inc.

  1. PARACOCCIDIOIDOMYCOSIS: CHALLENGES IN THE DEVELOPMENT OF A VACCINE AGAINST AN ENDEMIC MYCOSIS IN THE AMERICAS

    PubMed Central

    TABORDA, Carlos. P.; URÁN, M.E.; NOSANCHUK, J. D.; TRAVASSOS, L.R.

    2015-01-01

    SUMMARY Paracoccidioidomycosis (PCM), caused by Paracoccidioides spp, is an important endemic mycosis in Latin America. There are two recognized Paracoccidioides species, P. brasiliensis and P. lutzii, based on phylogenetic differences; however, the pathogenesis and disease manifestations of both are indistinguishable at present. Approximately 1,853 (~51,2%) of 3,583 confirmed deaths in Brazil due to systemic mycoses from 1996-2006 were caused by PCM. Antifungal treatment is required for patients with PCM. The initial treatment lasts from two to six months and sulfa derivatives, amphotericin B, azoles and terbinafine are used in clinical practice; however, despite prolonged therapy, relapses are still a problem. An effective Th1-biased cellular immune response is essential to control the disease, which can be induced by exogenous antigens or modulated by prophylactic or therapeutic vaccines. Stimulation of B cells or passive transference of monoclonal antibodies are also important means that may be used to improve the efficacy of paracoccidioidomycosis treatment in the future. This review critically details major challenges facing the development of a vaccine to combat PCM. PMID:26465365

  2. T1/ST2 promotes T helper 2 cell activation and polyfunctionality in bronchopulmonary mycosis.

    PubMed

    Piehler, D; Grahnert, A; Eschke, M; Richter, T; Köhler, G; Stenzel, W; Alber, G

    2013-03-01

    Interleukin (IL)-33 enhances T helper (Th)2 immunity via its receptor T1/ST2. Infection with the yeast-like pathogen Cryptococcus neoformans is usually controlled by a Th1-mediated immune response. The mechanisms responsible for nonprotective Th2 immunity leading to allergic inflammation in pulmonary cryptococcosis are still not fully understood. Using a murine pulmonary model of C. neoformans infection, we report that T1/ST2 expression correlates with the intensity of Th2 activation, as demonstrated by the expression of CD25 and CD44 and downregulation of CD62L. Antigen-specific T1/ST2(+) Th cells are the primary source of the Th2 cytokines IL-5 and IL-13 as compared with wild-type T1/ST2(-) Th cells or Th cells from T1/ST2(-/-) mice. In addition, T1/ST2(+) Th cells almost exclusively contain bi- and trifunctional Th2 cytokine-producing Th cells compared with T1/ST2(-) Th cells or Th cells from T1/ST2(-/-) mice. Finally, T1/ST2-driven Th2 development resulted in defective pulmonary fungal control. These data demonstrate that T1/ST2 directs Th2 cell activation and polyfunctionality in allergic bronchopulmonary mycosis.

  3. PARACOCCIDIOIDOMYCOSIS: CHALLENGES IN THE DEVELOPMENT OF A VACCINE AGAINST AN ENDEMIC MYCOSIS IN THE AMERICAS.

    PubMed

    Taborda, Carlos P; Urán, M E; Nosanchuk, J D; Travassos, L R

    2015-09-01

    Paracoccidioidomycosis (PCM), caused by Paracoccidioides spp, is an important endemic mycosis in Latin America. There are two recognized Paracoccidioides species, P. brasiliensis and P. lutzii, based on phylogenetic differences; however, the pathogenesis and disease manifestations of both are indistinguishable at present. Approximately 1,853 (~51,2%) of 3,583 confirmed deaths in Brazil due to systemic mycoses from 1996-2006 were caused by PCM. Antifungal treatment is required for patients with PCM. The initial treatment lasts from two to six months and sulfa derivatives, amphotericin B, azoles and terbinafine are used in clinical practice; however, despite prolonged therapy, relapses are still a problem. An effective Th1-biased cellular immune response is essential to control the disease, which can be induced by exogenous antigens or modulated by prophylactic or therapeutic vaccines. Stimulation of B cells or passive transference of monoclonal antibodies are also important means that may be used to improve the efficacy of paracoccidioidomycosis treatment in the future. This review critically details major challenges facing the development of a vaccine to combat PCM.

  4. Effect of exposure method to Beauveria bassiana and conidia concentration on mortality, mycosis, and sporulation in cadavers of Chilo partellus (Lepidoptera: Pyralidae).

    PubMed

    Tefera, Tadele; Pringle, K L

    2003-10-01

    The effects of exposure methods, conidial concentrations, and temperature on mortality, mycosis and sporulation in second instar Chilo partellus cadavers infected by Beauveria bassiana was investigated in laboratory studies. Larvae directly sprayed with conidia, exposed to conidia-treated leaves, and dipped into conidial suspension resulted in high mortality (98-100%). The longest LT50 (3.5 days) and days to mortality (2.6 days) were observed in the treated-leaves exposure method. The shortest LT50 (1 day) and days to mortality (1 day) were recorded for the dipping method. With increasing conidial concentrations, there were decreasing LT50 and days to mortality. Larvae exposed to treated leaves and larvae directly sprayed with conidial suspensions produced high mycoses in cadavers. Exposure of larvae to treated-leaves resulted in high sporulation. At lower concentrations of conidia, both mycosis and sporulation in cadavers were high. The optimum temperature for mycosis was 20 and 15 degrees C for sporulation.

  5. Recommendations for the management of candidemia in adults in Latin America. Latin America Invasive Mycosis Network.

    PubMed

    Nucci, Marcio; Thompson-Moya, Luis; Guzman-Blanco, Manuel; Tiraboschi, Iris Nora; Cortes, Jorge Alberto; Echevarría, Juan; Sifuentes, Jose; Zurita, Jeannete; Santolaya, María E; Alvarado Matute, Tito; de Queiroz Telles, Flavio; Colombo, Arnaldo Lopes

    2013-01-01

    Candidemia is one of the most frequent opportunistic mycoses worldwide. Limited epidemiological studies in Latin America indicate that incidence rates are higher in this region than in the Northern Hemisphere. Diagnosis is often made late in the infection, affecting the initiation of antifungal therapy. A more scientific approach, based on specific parameters, for diagnosis and management of candidemia in Latin America is warranted. 'Recommendations for the diagnosis and management of candidemia' are a series of manuscripts that have been developed by members of the Latin America Invasive Mycosis Network. They aim to provide a set of best-evidence recommendations for the diagnosis and management of candidemia. This publication, 'Recommendations for the management of candidemia in adults in Latin America', was written to provide guidance to healthcare professionals on the management of adults who have, or who are at risk of, candidemia. Computerized searches of existing literature were performed by PubMed. The data were extensively reviewed and analyzed by members of the group. The group also met on two occasions to pose questions, discuss conflicting views, and deliberate on a series of management recommendations. 'Recommendations for the management of candidemia in adults in Latin America' includes prophylaxis, empirical therapy, therapy for proven candidemia, patient work-up following diagnosis of candidemia, duration of candidemia treatment, and central venous catheter management in patients with candidemia. This manuscript is the second of this series that deals with diagnosis and treatment of invasive candidiasis. Other publications in this series include: 'Recommendations for the diagnosis of candidemia in Latin America', 'Recommendations for the management of candidemia in children in Latin America', and 'Recommendations for the management of candidemia in neonates in Latin America'.

  6. Recommendations for the management of candidemia in neonates in Latin America. Latin America Invasive Mycosis Network.

    PubMed

    Santolaya, María E; Alvarado Matute, Tito; de Queiroz Telles, Flavio; Colombo, Arnaldo Lopes; Zurita, Jeannete; Tiraboschi, Iris Nora; Cortes, Jorge Alberto; Thompson-Moya, Luis; Guzman-Blanco, Manuel; Sifuentes, Jose; Echevarría, Juan; Nucci, Marcio

    2013-01-01

    Candidemia is one of the most frequent opportunistic mycoses worldwide. Limited epidemiological studies in Latin America indicate that incidence rates are higher in this region than in the Northern Hemisphere. Diagnosis is often made late in the infection, affecting the initiation of antifungal therapy. A more scientific approach, based on specific parameters, for diagnosis and management of candidemia in Latin America is warranted. 'Recommendations for the diagnosis and management of candidemia' are a series of manuscripts that have been developed by members of the Latin America Invasive Mycosis Network. They aim to provide a set of best-evidence recommendations for the diagnosis and management of candidemia. This publication, 'Recommendations for the management of candidemia in neonates in Latin America', was written to provide guidance to healthcare professionals on the management of neonates who have, or who are at risk of, candidemia. Computerized searches of existing literature were performed by PubMed. The data were extensively reviewed and analyzed by members of the group. The group also met on two occasions to pose questions, discuss conflicting views, and deliberate on a series of management recommendations. 'Recommendations for the management of candidemia in neonates in Latin America' includes prophylaxis, empirical therapy, therapy for proven candidemia, patient work-up following diagnosis of candidemia, central venous catheter management, and management of complications. This manuscript is the fourth of this series that deals with diagnosis and treatment of invasive candidiasis. Other publications in this series include: 'Recommendations for the diagnosis of candidemia in Latin America', 'Recommendations for the management of candidemia in adults in Latin America', and 'Recommendations for the management of candidemia in children in Latin America'.

  7. Recommendations for the diagnosis of candidemia in Latin America. Latin America Invasive Mycosis Network.

    PubMed

    Colombo, Arnaldo Lopes; Cortes, Jorge Alberto; Zurita, Jeannete; Guzman-Blanco, Manuel; Alvarado Matute, Tito; de Queiroz Telles, Flavio; Santolaya, María E; Tiraboschi, Iris Nora; Echevarría, Juan; Sifuentes, Jose; Thompson-Moya, Luis; Nucci, Marcio

    2013-01-01

    Candidemia is one of the most frequent opportunistic mycoses worldwide. Limited epidemiological studies in Latin America indicate that incidence rates are higher in this region than in the Northern Hemisphere. Diagnosis is often made late in the infection, affecting the initiation of antifungal therapy. A more scientific approach, based on specific parameters, for diagnosis and management of candidemia in Latin America is warranted. 'Recommendations for the diagnosis and management of candidemia' are a series of manuscripts that have been developed by members of the Latin America Invasive Mycosis Network. They aim to provide a set of best-evidence recommendations for the diagnosis and management of candidemia. This publication, 'Recommendations for the diagnosis of candidemia in Latin America', was written to provide guidance to healthcare professionals on the diagnosis of candidemia, as well as on the usefulness and application of susceptibility testing in patients who have a confirmed diagnosis of candidemia. Computerized searches of existing literature were performed by PubMed. The data were extensively reviewed and analyzed by members of the group. The group also met on two occasions to pose questions, discuss conflicting views, and deliberate on a series of management recommendations. 'Recommendations for the diagnosis of candidemia in Latin America' includes diagnostic methods used to detect candidemia, Candida species identification, and susceptibility testing. The availability of methods, their costs and treatment settings are considered. This manuscript is the first of this series that deals with diagnosis and treatment of invasive candidiasis. Other publications in this series include: 'Recommendations for the management of candidemia in adults in Latin America', 'Recommendations for the management of candidemia in children in Latin America', and 'Recommendations for the management of candidemia in neonates in Latin America'.

  8. Recommendations for the management of candidemia in children in Latin America. Latin America Invasive Mycosis Network.

    PubMed

    Santolaya, María E; de Queiroz Telles, Flavio; Alvarado Matute, Tito; Colombo, Arnaldo Lopes; Zurita, Jeannete; Tiraboschi, Iris Nora; Cortes, Jorge Alberto; Thompson-Moya, Luis; Guzman-Blanco, Manuel; Sifuentes, Jose; Echevarría, Juan; Nucci, Marcio

    2013-01-01

    Candidemia is one of the most frequent opportunistic mycoses worldwide. Limited epidemiological studies in Latin America indicate that incidence rates are higher in this region than in the Northern Hemisphere. Diagnosis is often made late in the infection, affecting the initiation of antifungal therapy. A more scientific approach, based on specific parameters, for diagnosis and management of candidemia in Latin America is warranted. 'Recommendations for the diagnosis and management of candidemia' are a series of manuscripts that have been developed by members of the Latin America Invasive Mycosis Network. They aim to provide a set of best-evidence recommendations for the diagnosis and management of candidemia. This publication, 'Recommendations for the management of candidemia in children in Latin America', was written to provide guidance to healthcare professionals on the management of children who have, or who are at risk of, candidemia. Computerized searches of existing literature were performed by PubMed. The data were extensively reviewed and analyzed by members of the group. The group also met on two occasions to pose questions, discuss conflicting views, and deliberate on a series of management recommendations. 'Recommendations for the management of candidemia in children in Latin America' includes prophylaxis, empirical therapy, therapy for proven candidemia, patient work-up following diagnosis of candidemia, duration of candidemia treatment, and central venous catheter management in children with candidemia. This manuscript is the third of this series that deals with diagnosis and treatment of invasive candidiasis. Other publications in this series include: 'Recommendations for the diagnosis of candidemia in Latin America', 'Recommendations for the management of candidemia in adults in Latin America', and 'Recommendations for the management of candidemia in neonates in Latin America'.

  9. Chronic paracoccidioidomycosis of the intestine as single organ involvement points to an alternative pathogenesis of the mycosis.

    PubMed

    Benard, G; Costa, A N; Leopércio, A P S; Vicentini, A P; Kono, A; Shikanai-Yasuda, M A

    2013-12-01

    Current knowledge on the natural history of paracoccidioidomycosis states that the chronic form of the disease results from reactivation of quiescent foci established years or decades before during the primary lung infection. Once reactivated, the fungi can disseminate to virtually any organ or system. We present herein two chronic paracoccidioidomycosis patients with a single organ involvement that points to an alternative pathogenesis of the mycosis. These patients suggest that the chronic form may also arise from reactivation of foci not confined to the lungs, due to the early dissemination of yeast cells during the primary infection.

  10. Clinical and immunological studies for 105 Japanese seropositive patients of epidermolysis bullosa acquisita examined at Kurume University.

    PubMed

    Hashimoto, Takashi; Jin, Zhexiong; Ishii, Norito

    2016-08-01

    Using our serological diagnostic criteria, we selected 105 Japanese patients with epidermolysis bullosa acquisita (EBA), an autoimmune bullous disease (AIBD) reacting with type VII collagen, from our cohort of 5063 AIBD patients. We examined the patients clinically and immunologically. We found diversity of clinical manifestations in both cutaneous and oral mucosal lesions and a high rate of inflammatory-type EBA patients in Japan. Common treatments were systemic steroids, followed by immunosuppressives, DDS, tetracycline/minocycline and colchicine. Immunological studies revealed that indirect immunofluorescence of 1M-NaCl-split skin, immunoblotting of dermal extract, and type VII collagen ELISA were sensitive methods, with possible multiplicity of circulating autoantibodies against other basement membrane autoantigens. The present study analyzed the largest cohort of EBA patients, confirming the scarcity of EBA (only 105 of the 5063 AIBD patients), and showed that the three serological tests are useful for the diagnosis of EBA.

  11. A homozygous nonsense mutation in the {beta}3 chain gene of laminin 5 (LAMB3) in herlitz junctional epidermolysis bullosa

    SciTech Connect

    Pulkkinen, L.; Christiano, A.M.; Uitto, J.

    1994-11-15

    Herlitz junctional epidermolysis bullosa (H-JEB) is a severe autosomal recessive disorder characterized by blister formation within the dermal-epidermal basement membrane. Based on immunofluorescence analysis recognizing laminin 5 epitopes (previously known as nicein/kalinin), the genes for this lamina lucida protein have been proposed as candidate genes in H-JEB. Amplification of mRNA by RT-PCR, followed by direct nucleotide sequencing, revealed a homozygous C-to T transition resulting in a premature termination codon (CGA{r_arrow}TGA) on both alleles. This mutation was verified at the genomic DNA level, and both parents were shown to be heterozygous carriers of the same mutation. This is the first description of a mutation in the laminin {beta}3 chain gene (LAMB3) of laminin 5 in an H-JEB patient. 15 refs., 2 figs.

  12. Allogeneic blood and bone marrow cells for the treatment of severe epidermolysis bullosa: repair of the extracellular matrix

    PubMed Central

    Tolar, Jakub; Wagner, John E

    2014-01-01

    Contrary to the prevailing professional opinion of the past few decades, recent experimental and clinical data support the fact that protein replacement therapy by allogeneic blood and marrow transplantation is not limited to freely diffusible molecules such as enzymes, but also large structural proteins such as collagens. A prime example is the cross-correction of type VII collagen deficiency in generalised severe recessive dystrophic epidermolysis bullosa, in which blood and marrow transplantation can attenuate the mucocutaneous manifestations of the disease and improve patients’ quality of life. Although allogeneic blood and marrow transplantation can improve the integrity of the skin and mucous membranes, today’s accomplishments are only the first steps on the long pathway to cure. Future strategies will be built on the lessons learned from these first transplant studies. PMID:24095195

  13. Dystrophic Epidermolysis Bullosa in Pregnancy: A Case Report of the Autosomal Dominant Subtype and Review of the Literature

    PubMed Central

    Herrell, Howard

    2014-01-01

    Epidermolysis bullosa (EB) is a group of inherited blistering skin diseases that vary widely in their pathogenesis and severity. There are three main categories of EB: simplex, junctional, and dystrophic. This classification is based on the level of tissue separation within the basement membrane zone and this is attributed to abnormalities of individual or several anchoring proteins that form the interlocking network spanning from the epidermis to the dermis underneath. Dystrophic EB results from mutations in COL7A1 gene coding for type VII collagen leading to blister formation within the dermis. Diagnosis ultimately depends on the patient's specific genetic mutation, but initial diagnosis can be made from careful examination and history taking. We present a pregnant patient known to have autosomal dominant dystrophic EB and discuss the obstetrical and neonatal outcome. The paper also reviews the current English literature on this rare skin disorder. PMID:24864146

  14. The challenges of meeting nutritional requirements in children and adults with epidermolysis bullosa: proceedings of a multidisciplinary team study day.

    PubMed

    Hubbard, L; Haynes, L; Sklar, M; Martinez, A E; Mellerio, J E

    2011-08-01

    This is a report of a study day held in London on 3 March 2010 to discuss measures with which to meet the nutritional requirements of patients with epidermolysis bullosa (EB). Members of national and international multidisciplinary teams (MDTs) caring for patients with EB attended this event. The study day focused on four challenging aspects of management intimately associated with nutritional status in EB, necessitating close cooperation between MDT members: iron-deficiency anaemia, gastrostomy placement and feeding, muscle mass and mobility, and dental health. The study day provided a unique forum for dietitians, doctors, nurses, physiotherapists, psychologists, psychotherapists, dentists, dental hygienists and occupational therapists to share knowledge and debate problems common to all who strive to promote best practice in this rare and complex group of conditions. © The Author(s). CED © 2011 British Association of Dermatologists.

  15. Instrument for scoring clinical outcome of research for epidermolysis bullosa: a consensus-generated clinical research tool.

    PubMed

    Schwieger-Briel, Agnes; Chakkittakandiyil, Ajith; Lara-Corrales, Irene; Aujla, Nimrita; Lane, Alfred T; Lucky, Anne W; Bruckner, Anna L; Pope, Elena

    2015-01-01

    Epidermolysis bullosa (EB) is a genetic condition characterized by skin fragility and blistering. There is no instrument available for clinical outcome research measurements. Our aim was to develop a comprehensive instrument that is easy to use in the context of interventional studies. Item collection was accomplished using a two-step Delphi Internet survey process for practitioners and qualitative content analysis of patient and family interviews. Items were reduced based on frequency and importance using a 4-point Likert scale and were subject to consensus (>80% agreement) using the nominal group technique. Pilot data testing was performed in 21 consecutive patients attending an EB clinic. The final score, Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa (iscorEB), is a combined score that contains clinician items grouped in five domains (skin, mucosa, organ involvement, laboratory abnormalities, and complications and procedures; maximum score 114) and patient-derived items (pain, itch, functional limitations, sleep, mood, and effect on daily and leisurely activities; maximum score 120). Pilot testing revealed that combined (see below) and subscores were able to differentiate between EB subtypes and degrees of clinical severity (EB simplex 21.7 ± 16.5, junctional EB 28.0 ± 20.7, dystrophic EB 57.3 ± 24.6, p = 0.007; mild 17.3 ± 9.6, moderate 41.0 ± 19.4, and severe 64.5 ± 22.6, p < 0.001). There was high correlation between clinician and patient subscores (correlation coefficient = 0.79, p < 0.001). iscorEB seems to be a sensitive tool in differentiating between EB types and across the clinical spectrum of severity. Further validation studies are needed. © 2014 Wiley Periodicals, Inc.

  16. Correlation between nutritional, hematological and infectious characteristics and classification of the type of epidermolysis bullosa of patients assisted at the Dermatology Clinic of the Hospital Universitário de Brasília.

    PubMed

    Sousa, Márcia Carolline dos Santos; Paula, Carmen Dea Ribeiro de; Tauil, Pedro Luiz; Costa, Izelda Maria Carvalho

    2015-01-01

    Epidermolysis bullosa comprises a group of phenotypically different genodermatosis, hereditary or acquired, characterized by skin fragility and subsequent formation of blisters in response to mechanical trauma, and which may also affect mucous membranes. This study aimed to analyze the relation between the nutritional, hematologic, infectious characteristics and the type of epidermolysis bullosa, through a descriptive case study based on data from medical records of 10 patients with epidermolysis bullosa assisted regularly at the Dermatology Clinic of the Hospital Universitário de Brasília. The old classification of the type of epidermolysis bullosa, weight and height, blood count, white blood cell count, platelet count and description of the type and frequency of secondary infections during the service were considered. We verified a predominance of iron deficiency anemia, chronic leukocytosis, thrombocytosis, chronic malnutrition, low height for age and thinness, and people with epidermolysis bullosa simplex exhibited appropriate relation between height/age and BMI/age. The non-specific skin infection was the most prevalent in both sexes. The severity of the type of epidermolysis bullosa and frequency of secondary infections did not form a directly proportional relation. The absence of direct proportion in all cases between the type of epidermolysis bullosa and the analysis parameters suggest a possible significant interference from other aspects such as the extent of the affected skin area, extracutaneous type of engagement and specific genetic mutation. The inclusion of these factors in the new classification proposed by Fine et al can contribute significantly to a better correlation of clinical parameters and appropriate preventive and therapeutic approaches.

  17. Botulinum toxin A injection for chronic anal fissures and anal sphincter spasm improves quality of life in recessive dystrophic epidermolysis bullosa.

    PubMed

    Chaptini, Cassandra; Casey, Genevieve; Harris, Adam G; Wattchow, David; Gordon, Lynne; Murrell, Dedee F

    2015-12-01

    We report a 20-year-old female with generalized, severe, recessive dystrophic epidermolysis bullosa who developed secondary chronic anal fissures. This resulted in anal sphincter spasm and severe, disabling pain. She was treated with five botulinum toxin A injections into the internal anal sphincter over a period of 2 years and gained marked improvement in her symptoms. This case demonstrates the successful use of botulinum toxin A injections to relieve anal sphincter spasm and fissuring, with long-term improvement.

  18. Dystrophic Epidermolysis Bullosa: COL7A1 Mutation Landscape in a Multi-Ethnic Cohort of 152 Extended Families with High Degree of Customary Consanguineous Marriages.

    PubMed

    Vahidnezhad, Hassan; Youssefian, Leila; Zeinali, Sirous; Saeidian, Amir Hossein; Sotoudeh, Soheila; Mozafari, Nikoo; Abiri, Maryam; Kajbafzadeh, Abdol-Mohammad; Barzegar, Mohammadreza; Ertel, Adam; Fortina, Paolo; Uitto, Jouni

    2017-03-01

    Dystrophic epidermolysis bullosa is a heritable skin disease manifesting with sub-lamina densa blistering, erosions, and chronic ulcers. COL7A1, encoding type VII collagen, has been identified as the candidate gene for dystrophic epidermolysis bullosa. In this study, we have identified COL7A1 mutations in a large multi-ethnic cohort of 152 extended Iranian families with high degree of consanguinity. The patients were diagnosed by clinical manifestations, histopathology, and immunoepitope mapping. Mutation detection consisted of a combination of single nucleotide polymorphism-based whole-genome homozygosity mapping, Sanger sequencing, and gene-targeted next-generation sequencing. A total of 104 distinct mutations in COL7A1 were identified in 149 of 152 families (98%), 56 (53%) of them being previously unreported. Ninety percent of these mutations were homozygous recessive, reflecting consanguinity in these families. Three recurrent mutations were identified in five or more families, and haplotype analysis suggested a founder effect in two of them. In conclusion, COL7A1 harbored mutations in the overwhelming majority of patients with dystrophic epidermolysis bullosa, and most of them in this Iranian cohort were consistent with autosomal recessive inheritance. The mutation profile attests to the impact of consanguinity in these families. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. The Syk Tyrosine Kinase Is Required for Skin Inflammation in an In Vivo Mouse Model of Epidermolysis Bullosa Acquisita.

    PubMed

    Németh, Tamás; Virtic, Oana; Sitaru, Cassian; Mócsai, Attila

    2017-10-01

    The inflammatory form of epidermolysis bullosa acquisita is caused by autoantibodies against type VII collagen (C7), a component of the dermal-epidermal junction. We have previously shown that myeloid Src family kinases mediate skin inflammation triggered by anti-C7 antibodies. Here we identify the Syk tyrosine kinase as a critical component of autoantibody-induced skin inflammation downstream of Src family kinases. Immobilized C7-anti-C7 immune complexes triggered neutrophil activation and Syk phosphorylation in a Src family kinase-dependent manner. Bone marrow chimeric mice lacking Syk in their hematopoietic compartment were completely protected from skin inflammation triggered by anti-C7 antibodies despite normal circulating anti-C7 levels. Syk deficiency abrogated the accumulation of CXCL2, IL-1β, and leukotriene B4 at the site of inflammation and resulted in defective in vivo neutrophil recruitment. Syk(-/-) neutrophils had a normal intrinsic migratory capacity but failed to release CXCL2 or leukotriene B4 upon activation by immobilized C7-anti-C7 immune complexes, indicating a role for Syk in the amplification of the inflammation process. These results identify Syk as a critical component of skin inflammation in a mouse model of epidermolysis bullosa acquisita and as a potential therapeutic target in epidermolysis bullosa acquisita and other mechanistically related inflammatory skin diseases such as bullous pemphigoid. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. [Epidemiological aspects of cutaneous mycosis of HIV-infected patients in the National Referral Center of Burkina Faso, West Africa].

    PubMed

    Zida, A; Sawadogo, P M; Diallo, I; Tapsoba, H; Bazie, Z; Drabo, Y J; Guiguemde, T R

    2016-06-01

    Our study aimed to analyze the epidemiological aspects of cutaneous mycosis in people living with human immunodeficiency virus (PLHIV). This is a descriptive study of 382 patients living with HIV. Following an investigation into the risk factors, mycological samples have been performed. Each sample underwent direct examination and cultivation for the identification of fungal species. The Blastese test is used for the identification of Candida albicans. One hundred and six (106) of the 382 people living with human immunodeficiency virus undergo a mycological collection of which 76 gave a positive result. The overall prevalence of cutaneous mycosis was 19.9 %. It was significantly higher in women and in patients who had a CD4 count ≤500/mm3. C. albicans and Trichophyton rubrum were the most isolated species with 22.4 and 19.8 % of all fungal species isolated, respectively. Cutaneous mycoses are common among people living with human immunodeficiency virus and whose CD4 count ≤ 500/mm(3). Copyright © 2016. Published by Elsevier Masson SAS.

  1. Antifungal Potential and Antioxidant Efficacy in the Shell Extract of Cocos nucifera (L.) (Arecaceae) against Pathogenic Dermal Mycosis

    PubMed Central

    Khalid Thebo, Nasreen; Ahmed Simair, Altaf; Sughra Mangrio, Ghulam; Ansari, Khalil Ahmed; Ali Bhutto, Aijaz; Lu, Changrui; Ali Sheikh, Wazir

    2016-01-01

    Background: Coconut is a tropical fruit well known for its essential oils that have been recognized for their biological activities since ancient times. There have been no previous investigations on the essential oils from coconut shells. Method: The shell extract of Cocos nucifera (L.) was prepared by the Soxhlet method and total phenolic content (TPC) in the extract was determined by Folin-Ciocalteu (FC) assay. The antioxidant potential of the coconut shell extract was evaluated by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Minimum inhibitory concentration (MIC) of the extract was determined by the strip method against clinically isolated dermal mycosis of 20 infected patients. Result: Total antioxidant activity varied from 92.32% to 94.20% and total phenolic content was found at 5.33 ± 0.02 mg/g in the coconut shell extract. The extract was found to be most effective as an antifungal against human pathogenic fungi, including A. niger, A. flavus, T. rubrum, M. canis, M. gypseum, A. fumigates, T. mentagrophyte and T. vercossum. The crude shell extract was highly effective against all dermal mycosis tested with the MIC ranging from 62 mm to 90 mm, whereas all fungal samples showed good inhibitory effect. Conclusion: The results of the present study provide a potential cure for microbial infections. PMID:28930122

  2. Antifungal Potential and Antioxidant Efficacy in the Shell Extract of Cocos nucifera (L.) (Arecaceae) against Pathogenic Dermal Mycosis.

    PubMed

    Khalid Thebo, Nasreen; Ahmed Simair, Altaf; Sughra Mangrio, Ghulam; Ansari, Khalil Ahmed; Ali Bhutto, Aijaz; Lu, Changrui; Ali Sheikh, Wazir

    2016-05-25

    Background: Coconut is a tropical fruit well known for its essential oils that have been recognized for their biological activities since ancient times. There have been no previous investigations on the essential oils from coconut shells. Method: The shell extract of Cocos nucifera (L.) was prepared by the Soxhlet method and total phenolic content (TPC) in the extract was determined by Folin-Ciocalteu (FC) assay. The antioxidant potential of the coconut shell extract was evaluated by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Minimum inhibitory concentration (MIC) of the extract was determined by the strip method against clinically isolated dermal mycosis of 20 infected patients. Result: Total antioxidant activity varied from 92.32% to 94.20% and total phenolic content was found at 5.33 ± 0.02 mg/g in the coconut shell extract. The extract was found to be most effective as an antifungal against human pathogenic fungi, including A. niger, A. flavus, T. rubrum, M. canis, M. gypseum, A. fumigates, T. mentagrophyte and T. vercossum. The crude shell extract was highly effective against all dermal mycosis tested with the MIC ranging from 62 mm to 90 mm, whereas all fungal samples showed good inhibitory effect. Conclusion: The results of the present study provide a potential cure for microbial infections.

  3. Birmingham epidermolysis severity score and vitamin D status are associated with low BMD in children with epidermolysis bullosa.

    PubMed

    Rodari, G; Guez, S; Manzoni, F; Chalouhi, K K; Profka, E; Bergamaschi, S; Salera, S; Tadini, G; Ulivieri, F M; Spada, A; Giavoli, C; Esposito, S

    2017-04-01

    Bone status impairment represents a complication of generalized forms of epidermolysis bullosa (EB); however, the prevalence and the main determinants of this event in localized forms remain poorly defined. Birmingham epidermolysis bullosa severity (BEBS) score and 25-hydroxyvitamin D levels are strongly associated with low bone mass, suggesting that vitamin D may play a potential beneficial role in bone health. Further longitudinal studies are needed in order to confirm this hypothesis. Bone status impairment represents a complication of generalized forms of EB; thus, we aimed to estimate the prevalence of low bone mass, to examine mineralization differences in various EB subtypes and to identify the most important determinants of bone impairment in children with either generalized or localized EB. An observational study of 20 children (11 males; mean age ± standard deviation, 11.7 ± 3.9 years) with EB was performed. Clinical history, physical examination, laboratory studies, X-ray of the left hand and wrist for bone age, and dual energy X-ray absorptiometry scans of the lumbar spine were obtained. Areal bone mineral density (aBMD Z-scores) and bone mineral apparent density were related to the BEBS score. Areal BMD Z-score (mean -1.82 ± 2.33, range, -7.6-1.7) was reduced (<-2 SD) in 8 patients (40%), whereas aBMD Z-score adjusted for bone age was low in 7 patients (35%). BEBS score and 25-hydroxyvitamin D serum levels were the most important elements associated with aBMD (P = 0.0001 and P = 0.016, respectively). A significant correlation between the aBMD Z-score and area of skin damage, insulin-like growth factor-1, C-reactive protein, and sodium serum levels was also found. Low aBMD can be considered a systemic complication of EB, primarily associated with BEBS score and 25-hydroxyvitamin D levels. Therefore, longitudinal evaluation of bone status is ongoing in these patients to define whether vitamin D supplementation would prevent, or at least

  4. Epidermolysis bullosa House Austria and Epidermolysis bullosa clinical network : Example of a centre of expertise implemented in a European reference network to face the burden of a rare disease.

    PubMed

    Laimer, Martin; Pohla-Gubo, Gabriela; Diem, Anja; Prodinger, Christine; Bauer, Johann W; Hintner, Helmut

    2017-01-01

    Accurately addressing the diverse and complex issues of rare diseases (RD) in terms of prevention, recognition, diagnosis, treatment, care and research along key RD specificities, such as great heterogeneity, a limited number of patients, scarcity of relevant knowledge and expertise as well as enormous costs for patient care is a challenging task for healthcare providers and authorities that makes a supranational approach particularly feasible. The European Union has acknowledged RD matters by several initiatives, including efforts to implement national centres of expertise and European reference networks as well as a cross-border referral mechanism to foster access to expert services and to boost dissemination of clinical expertise and research activities. Exemplified by the EB House Austria, a centre of expertise for epidermolysis bullosa cross-linked with international reference partner institutions, this strategy proves its potential to be translated into optimized patient care and to meet the major medical, scientific, social and health-economic impact of RD.

  5. Compound Heterozygosity of Dominant and Recessive COL7A Alleles in a Severely Affected Patient with a Family History of Dystrophic Epidermolysis Bullosa: Clinical Findings, Genetic Testing, and Treatment Implications.

    PubMed

    Watson, Kendra D; Schoch, Jennifer J; Beek, Geoffrey J; Hand, Jennifer L

    2017-03-01

    An 8-year-old girl born to a family with more than three generations of dominant dystrophic epidermolysis bullosa (DDEB) presented with life-threatening confluent skin erosions, mitten hand deformity, and failure to thrive. Reassessment of her family history and genetic testing showed compound heterozygous COL7A mutations, one inherited from her DDEB-affected mother and one from her unaffected, healthy father. This family illustrates the risk of unexpected, severe, autosomal recessive epidermolysis bullosa (EB) in a family with milder, multigenerational autosomal dominant EB. Clinicians should recognize the clinical spectrum of dystrophic EB and recommend genetic consultation when the phenotype conflicts with family history.

  6. Sustained phenotypic reversion of junctional epidermolysis bullosa dog keratinocytes: Establishment of an immunocompetent animal model for cutaneous gene therapy

    SciTech Connect

    Spirito, Flavia; Capt, Annabelle; Rio, Marcela Del; Larcher, Fernando; Guaguere, Eric; Danos, Olivier; Meneguzzi, Guerrino . E-mail: meneguzz@unice.fr

    2006-01-20

    Gene transfer represents the unique therapeutic issue for a number of inherited skin disorders including junctional epidermolysis bullosa (JEB), an untreatable genodermatose caused by mutations in the adhesion ligand laminin 5 ({alpha}3{beta}3{gamma}2) that is secreted in the extracellular matrix by the epidermal basal keratinocytes. Because gene therapy protocols require validation in animal models, we have phenotypically reverted by oncoretroviral transfer of the curative gene the keratinocytes isolated from dogs with a spontaneous form of JEB associated with a genetic mutation in the {alpha}3 chain of laminin 5. We show that the transduced dog JEB keratinocytes: (1) display a sustained secretion of laminin 5 in the extracellular matrix; (2) recover the adhesion, proliferation, and clonogenic capacity of wild-type keratinocytes; (3) generate fully differentiated stratified epithelia that after grafting on immunocompromised mice produce phenotypically normal skin and sustain permanent expression of the transgene. We validate an animal model that appears particularly suitable to demonstrate feasibility, efficacy, and safety of genetic therapeutic strategies for cutaneous disorders before undertaking human clinical trials.

  7. Progress toward Treatment and Cure of Epidermolysis Bullosa: Summary of the DEBRA International Research Symposium EB2015.

    PubMed

    Uitto, Jouni; Bruckner-Tuderman, Leena; Christiano, Angela M; McGrath, John A; Has, Cristina; South, Andrew P; Kopelan, Brett; Robinson, E Clare

    2016-02-01

    Epidermolysis bullosa (EB), a group of complex heritable blistering diseases, is the topic of triennial research meetings organized by DEBRA International, Vienna, Austria, the network of national EB patient advocacy organizations. The DEBRA 2015 Research Conference, held in May 2015, brought together investigators and clinicians from around the world working at the forefront of EB research. Discussing the state-of-the-art approaches from a wide range of disciplines, there was a palpable excitement at this conference brought about by the optimism about applying new sequencing techniques, genome editing, protein replacement, autologous and allogeneic stem cell therapy, innovations in cancer biology, revertant mosaicism, and induced pluripotent stem cell techniques, all of which are aimed at developing new therapies for EB. Many in the field who have participated in EB research for many years were especially enthusiastic and felt that, possibly for the first time, the field seems uniquely poised to bring these new tools to effectively tackle EB. Multiple complementary approaches are currently in motion toward improved quality of life and eventually a cure for patients suffering from EB, a currently intractable disease.

  8. [INFLUENCE OF THE CHANGE OF TREATMENT ON QUALITY OF LIFE OF AN ADULT PATIENT WITH EPIDERMOLYSIS BULLOSA. CLINICAL CASE].

    PubMed

    Aguilar Vega, Francisca Aguilar; Sánchez Hernández, María del Mar; López Pérez, María Soledad

    2016-04-01

    Epidermolysis bullosa is a genetic disease characterized by an alteration in the proteins involved in the binding of the dermis to the epidermis. It can also affect the mucous, causing inner injuries. It is classified into three main types: simple, junctional and dystrophic, and, depending on its inheritance, can be dominant and recessive. There is no specific treatment and its evolution is chronic, significantly affecting the quality of life of patients. The caretaking required by people with this disease is a real challenge for the nursing professional and it is very important to have the support of his family. In our case we explain how we got to modify the healthcare that this patient received for years, who was averse to changes, both himself and his family. Counseled by DEBRA nurses, the association of those affected by this disease and their families, and also by a cures-specialist nurse that DEBRA introduced to us, they helped us convincing thepatient and his family of the need of changing the hydrophilic cotton gauze dipped in antibiotic ointment with different concentrations depending on the zone, to more advanced cures, with dressings for wound healing in a moist environment, gaining time and comfort, given that previous cures were slow and painful. The pain, odor and time needed for healing has decreased. The patient has gained comfort by reducing the time spent on cures. Nursing has achieved its goal to improve the quality of the patient's life.

  9. Treatment of dystrophic epidermolysis bullosa with bone marrow non-hematopoeitic stem cells: a randomized controlled trial.

    PubMed

    El-Darouti, Mohammad; Fawzy, Marwa; Amin, Iman; Abdel Hay, Rania; Hegazy, Rehab; Gabr, Hala; El Maadawi, Zeinab

    2016-01-01

    Patients with dystrophic epidermolysis bullosa (DEB) have mutations in type VII collagen gene. Type VII collagen is synthesized by keratinocytes and fibroblasts. Based on the ability of bone marrow non-hematopoeitic stem cells (NHBMSC) to develop into fibroblasts, we decided to investigate the use of NHBMSC in the treatment of recessive DEB (RDEB). This study included fourteen patients with RDEB; the first seven of them were given cyclosporine after the infusion of NHBMSC. As cyclosporine has been used for the treatment of RDEB we decided not to use cyclosporine for the second group of seven patients. Skin biopsies from the lesions were studied by electron microscopy before and after treatment. The number of new blisters decreased significantly after treatment in both groups (p = 0.003 and 0.004 respectively) and the rate of healing of new blisters became significantly faster after treatment in both groups (p < 0.001) with no significant difference between the two groups. Electron microscopic examination revealed increased number of anchoring fibrils after treatment in both groups. No major side effects were reported during the 1-year follow-up period. Our findings highlight the efficacy as well as the safety of NHBMSC in the treatment of RDEB.

  10. Recessive dystrophic epidermolysis bullosa: case of non-Hallopeau-Siemens variant with premature termination codons in both alleles.

    PubMed

    Yonei, Nozomi; Ohtani, Toshio; Furukawa, Fukumi

    2006-11-01

    Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the COL7A1 gene encoding collagen, the major component of anchoring fibrils. Premature termination codon (PTC) mutations in both alleles usually lead to the Hallopeau-Siemens variant that shows the most severe phenotype. We experienced a case of the non-Hallopeau-Siemens variant (nHS-RDEB), which had a mild clinical severity although it has PTC mutations in both alleles. Our patient was a compound heterozygote for a nonsense mutation (R669X) in exon 15 and a nonsense mutation (E2857X) in exon 116. But we confirmed the existence of some anchoring fibrils on electron micrograph. This suggested that a PTC close to the 3' end of COL7A1 does not completely abolish the collagen VII mRNA. We hypothesized that the truncated procollagen VII from the mutant allele with a nonsense mutation (E2857X) in exon 116 included two out of eight cysteines needed for disulfide bond formation, and hence a few functional anchoring fibrils could be formed.

  11. Hallopeau-Siemens dystrophic epidermolysis bullosa due to homozygous 5818delC mutation in the COL7A gene.

    PubMed

    Koshida, Shigeki; Tsukamura, Atsushi; Yanagi, Takahide; Nakahara, Sayuri; Takeuchi, Yoshihiro; Kato, Takashi; Tanaka, Toshihiro; Nakano, Hajime; Shimizu, Hiroshi

    2013-04-01

    Epidermolysis bullosa (EB) is a group of inherited mechanobullous skin disease. The dystrophic EB (DEB), one subtype of EB, is inherited in an autosomal dominant DEB or in an autosomal recessive (RDEB). DEB is caused by mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils. Over 300 pathogenic mutations have been detected within COL7A in DEB. Patients with the Hallopeau-Siemens type (HS-RDEB), most severe form of DEB, frequently have premature termination codon (PTC) mutations on both alleles. PTC mutations on both alleles result in depleted mRNA and α1 helix, and failure to form the triple helix structure characteristic of type VII collagen. As patients with HS-RDEB usually have a pair of heterozygous PTC mutations, there have been rarely reported homozygous ones in HS-RDEB. We report the first case of HS-RDEB homozygous PTC mutations of 5818delC in both COL7A1 alleles. This case report suggests the positional effect of PTC mutations and vigilance against early infantile death in EB including HS-RDEB.

  12. Premature termination codons in the Type VII collagen gene (COL7A1) underlie severe, mutilating recessive dystrophic epidermolysis bullosa

    SciTech Connect

    Christiano, A.M.; Uitto, J. ); Anhalt, G. ); Gibbons, S.; Bauer, E.A. )

    1994-05-01

    Epidermolysis bullosa (EB) is a group of heritable mechano-bullous skin diseases classified into three major categories on the basis of the level of tissue separation within the dermal-epidermal basement membrane zone. The most severe, dystrophic (scarring) forms of EB demonstrate blister formation below the cutaneous basement membrane at the level of the anchoring fibrils. Ultrastructural observations of altered anchoring fibrils and genetic linkage to the gene encoding type VII collagen (COL7A1), the major component of anchoring fibrils, have implicated COL7A1 as the candidate gene in the dystrophic forms of EB. The authors have recently cloned the entire cDNA and gene for human COL7A1, which has been mapped to 3p21. In this study, they describe mutations in four COL7A1 alleles in three patients with severe, mutilating recessive dystrophic EB (Hallopeau-Siemens type, HS-RDEB). Each of these mutations resulted in a premature termination codon (PTC) in the amino-terminal portion of COL7A1. One of the patients was a compound heterozygote for two different mutations. The heterozygous carriers showed an [approximately] 50% reduction in anchoring fibrils, yet were clinically unaffected. Premature termination codons in both alleles of COL7A1 may thus be a major underlying cause of the severe, recessive dystrophic forms of EB. 40 refs., 8 figs.

  13. Efficient KRT14 Targeting and Functional Characterization of Transplanted Human Keratinocytes for the Treatment of Epidermolysis Bullosa Simplex

    PubMed Central

    Petek, Lisa M; Fleckman, Philip; Miller, Daniel G

    2010-01-01

    Inherited skin blistering conditions collectively named epidermolysis bullosa (EB) cause significant morbidity and mortality due to the compromise of the skin's barrier function, the pain of blisters, inflammation, and in some cases scaring and cancer. The simplex form of EB is usually caused by dominantly inherited mutations in KRT5 or KRT14. These mutations result in the production of proteins with dominant-negative activity that disrupt polymerization of intermediate filaments in the basal keratinocyte layer and result in a weak epidermal–dermal junction. The genome of adeno-associated virus (AAV) vectors can recombine with chromosomal sequence so that mutations can be corrected, or production of proteins with dominant-negative activity can be disrupted. We demonstrate a clinically feasible strategy for efficient targeting of the KRT14 gene in normal and EB-affected human keratinocytes. Using a gene-targeting vector with promoter trap design, targeted alteration of one allele of KRT14 occurred in 100% of transduced cells and transduction frequencies ranged from 0.1 to 0.6% of total cells. EBS patient keratinocytes with precise modifications of the mutant allele are preferentially recovered from targeted cell populations. Single epidermal stem cell clones produced histologically normal skin grafts after transplantation to athymic mice and could generate a sufficient number of cells to transplant the entire skin surface of an individual. PMID:20571545

  14. Lysyl Hydroxylase 3 Localizes to Epidermal Basement Membrane and Is Reduced in Patients with Recessive Dystrophic Epidermolysis Bullosa.

    PubMed

    Watt, Stephen A; Dayal, Jasbani H S; Wright, Sheila; Riddle, Megan; Pourreyron, Celine; McMillan, James R; Kimble, Roy M; Prisco, Marco; Gartner, Ulrike; Warbrick, Emma; McLean, W H Irwin; Leigh, Irene M; McGrath, John A; Salas-Alanis, Julio C; Tolar, Jakub; South, Andrew P

    2015-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 protein. Exogenous type VII collagen did not alter LH3 expression in cultured RDEB keratinocytes and we show that RDEB patients receiving bone marrow transplantation who demonstrate significant increase in type VII collagen do not show increased levels of LH3 at the basement membrane. Our data report a direct link between LH3 and endogenous type VII collagen expression concluding that reduction of LH3 at the basement membrane in patients with RDEB will likely have significant implications for disease progression and therapeutic intervention.

  15. Betulin-Based Oleogel to Improve Wound Healing in Dystrophic Epidermolysis Bullosa: A Prospective Controlled Proof-of-Concept Study

    PubMed Central

    Kiritsi, Dimitra; Schempp, Christoph; Has, Cristina; Schumann, Hauke

    2017-01-01

    Introduction Skin fragility and recurrent wounds are hallmarks of hereditary epidermolysis bullosa (EB). Treatment options to accelerate wound healing are urgently needed. Oleogel-S10 contains a betulin-rich triterpene extract from birch bark. In this study, we tested the wound healing properties of topical Oleogel-S10 in patients with dystrophic EB. Methods We conducted an open, blindly evaluated, controlled, prospective phase II pilot trial in patients with dystrophic EB (EudraCT number 2010-019945-24). Healing of wounds treated with and without topical Oleogel-S10 was compared. Primary efficacy variable was faster reepithelialization as determined by 2 blinded experts. The main secondary outcome variable of the study was percentage of wound epithelialization. Results Twelve wound pairs of 10 patients with dystrophic EB were evaluated. In 5 of 12 cases, both blinded reviewers considered epithelialization of the intervention wounds as superior. In 3 cases, only one reviewer considered Oleogel-S10 as superior and the other one as equal to control. Measurements of wound size showed a trend towards accelerated wound healing with the intervention but without reaching statistical significance. Conclusion Our results indicate a potential for faster reepithelialization of wounds in patients with dystrophic EB when treated with Oleogel-S10 but larger studies are needed to confirm significance. PMID:28611842

  16. Nonsense variant in COL7A1 causes recessive dystrophic epidermolysis bullosa in Central Asian Shepherd dogs.

    PubMed

    Niskanen, Julia; Dillard, Kati; Arumilli, Meharji; Salmela, Elina; Anttila, Marjukka; Lohi, Hannes; Hytönen, Marjo K

    2017-01-01

    A rare hereditary mechanobullous disorder called epidermolysis bullosa (EB) causes blistering in the skin and the mucosal membranes. To date, nineteen EB-related genes have been discovered in human and other species. We describe here a novel EB variant in dogs. Two newborn littermates of Central Asian Shepherd dogs with severe signs of skin blistering were brought to a veterinary clinic and euthanized due to poor prognosis. In post-mortem examination, the puppies were shown to have findings in the skin and the mucosal membranes characteristic of EB. A whole-genome sequencing of one of the affected puppies was performed to identify the genetic cause. The resequencing data were filtered under a recessive model against variants from 31 other dog genomes, revealing a homozygous case-specific nonsense variant in one of the known EB-causing genes, COL7A1 (c.4579C>T, p.R1527*). The variant results in a premature stop codon and likely absence of the functional protein in the basement membrane of the skin in the affected dogs. This was confirmed by immunohistochemistry using a COL7A1 antibody. Additional screening of the variant indicated full penetrance and breed specificity at ~28% carrier frequency. In summary, this study reveals a novel COL7A1 variant causing recessive dystrophic EB and provides a genetic test for the eradication of the disease from the breed.

  17. Role of dystrophic epidermolysis bullosa in anxiety, depression and self-esteem: A controlled cross-sectional study.

    PubMed

    Fortuna, Giulio; Aria, Massimo; Cepeda-Valdes, Rodrigo; Garcia-Garcia, Sandra Cecilia; Moreno Trevino, Maria Guadalupe; Salas-Alanís, Julio Cesar

    2016-01-01

    The psychological aspect in patients with dystrophic epidermolysis bullosa (DEB) is poorly documented. We sought to determine the role of DEB in anxiety, depression and self-esteem. We conducted a cross-sectional study, collecting data from 27 DEB patients and 26 healthy individuals. DEB patients and healthy controls completed three different psychometric scales for anxiety and depression and one scale for self-esteem. DEB patients and healthy controls were homogeneous for age and sex (P > 0.05), but not for employment, marital status and economic level (P < 0.05). Median values of all psychometric battery scales were not statistically significant between DEB patients and healthy controls, except for Goldberg scale for anxiety (P = 0.003) and depression (P = 0.037) and slightly significant for Zung Scale for anxiety (P = 0.048) with no difference between DEB patients with dominant versus recessive form in all scales (P > 0.05). Among DEB patients, only employment showed a significant difference in all scales (P < 0.05) but Hamilton for depression, whereas self-esteem seemed to be affected by marriage (P = 0.04) and education (P = 0.016). DEB patients apparently are not more anxious and/or depressed and do not have less self-esteem than healthy individuals. © 2015 Japanese Dermatological Association.

  18. Discovering potential drug-targets for personalized treatment of autoimmune disorders - what we learn from epidermolysis bullosa acquisita.

    PubMed

    Witte, Mareike; Koga, Hiroshi; Hashimoto, Takashi; Ludwig, Ralf J; Bieber, Katja

    2016-08-01

    Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune bullous dermatosis (AIBD). Treatment of EBA is challenging and mostly relies on systemic immunosuppression. During the last decade, intensive research led to the identification of new potential therapeutic targets that interfere in different phases of disease progression. Therapeutic interventions acting upon these candidate drug targets in animal models of EBA, such as cytokine-modulating biologics and small molecules, have validated them as potential new therapeutic strategies for EBA patients. In this paper, we review the current treatments for EBA, describe the pathogenesis of the disease, and finally specify new drug candidates for the development of a more specific therapy with minimized side-effects for EBA and potentially other autoimmune diseases. We currently understand EBA as a disease that evolves from the interplay of many different signaling pathways. These signaling pathways, which are described in this review, provide new targets for EBA treatment. The ultimate goal of this research field is the development of specific, pathogenesis-based therapeutic strategies. Through identification of up- or downregulated pathways that dominate disease progression in individual patients, we expect therapy in EBA to become more and more precise and move towards a patient-based therapy.

  19. Cloning of the {beta}3 chain gene (LAMB3) of human laminin 5, a candidate gene in junctional epidermolysis bullosa

    SciTech Connect

    Pulkkinen, L.; Christiano, A.M.; Uitto, J.

    1995-01-01

    Laminin 5 consists of three polypeptides, {alpha}3, {beta}3, and {gamma}2, encoded by the genes LAMA3, LAMB3, and LAMC2, respectively. In this study, we have elucidated the exon-intron organization of the human LAMB3 gene. Characterization of five overlapping {lambda} phage DNA clones revealed that the gene was approximately 29 kb in size. Subsequent sequence data revealed that the gene consisted of 23 exons that varied from 64 to 379 bp in size, accounting for the full-length cDNA with an open reading frame of 3516 hp encoding 1172 amino acids. Comparison of the LAMB3 gene structure with the previously characterized LAMB1 gene revealed that LAMB3 was considerably more compact. Knowledge of the exon-intron organization of the LAMB3 gene will facilitate elucidation of mutations in patients with the junctional forms of epidermolysis bullosa, some of which have been associated with mutations in the laminin 5 genes. 33 refs., 3 figs., 2 tabs.

  20. Progress Towards Treatment and Cure of Epidermolysis Bullosa: Summary of the DEBRA International Research Symposium EB2015

    PubMed Central

    Uitto, Jouni; Tuderman, Leena Bruckner; Christiano, Angela M.; McGrath, John A.; Has, Cristina; South, Andrew P.; Kopelan, Brett; Robinson, E. Clare

    2015-01-01

    Epidermolysis bullosa (EB), a group of complex heritable blistering diseases, is the topic of triennial research meetings organized by DEBRA International, the umbrella of patient advocacy organizations. The DEBRA 2015 Research Conference, held in May 2015, brought together investigators and clinicians from around the world working at the forefront of EB research. Discussing the state-of-the-art approaches from a wide range of disciplines, there was a palpable excitement at this conference brought about by the optimism about applying new sequencing techniques, genome editing, protein replacement, autologous and allogeneic stem cell therapy, innovations in cancer biology, revertant mosaicism and iPSC techniques, all of which are aimed at developing new therapies for EB. Many in the field who have participated in EB research for many years were especially enthusiastic and felt that, possibly for the first time, the field seems uniquely poised to bring these new tools to effectively tackle EB using multiple complementary approaches towards improved quality of life and eventually a cure for patients suffering from EB, a currently intractable disease. PMID:26802230

  1. Site-specific genome editing for correction of induced pluripotent stem cells derived from dominant dystrophic epidermolysis bullosa.

    PubMed

    Shinkuma, Satoru; Guo, Zongyou; Christiano, Angela M

    2016-05-17

    Genome editing with engineered site-specific endonucleases involves nonhomologous end-joining, leading to reading frame disruption. The approach is applicable to dominant negative disorders, which can be treated simply by knocking out the mutant allele, while leaving the normal allele intact. We applied this strategy to dominant dystrophic epidermolysis bullosa (DDEB), which is caused by a dominant negative mutation in the COL7A1 gene encoding type VII collagen (COL7). We performed genome editing with TALENs and CRISPR/Cas9 targeting the mutation, c.8068_8084delinsGA. We then cotransfected Cas9 and guide RNA expression vectors expressed with GFP and DsRed, respectively, into induced pluripotent stem cells (iPSCs) generated from DDEB fibroblasts. After sorting, 90% of the iPSCs were edited, and we selected four gene-edited iPSC lines for further study. These iPSCs were differentiated into keratinocytes and fibroblasts secreting COL7. RT-PCR and Western blot analyses revealed gene-edited COL7 with frameshift mutations degraded at the protein level. In addition, we confirmed that the gene-edited truncated COL7 could neither associate with normal COL7 nor undergo triple helix formation. Our data establish the feasibility of mutation site-specific genome editing in dominant negative disorders.

  2. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa.

    PubMed

    Sebastiano, Vittorio; Zhen, Hanson Hui; Haddad, Bahareh; Derafshi, Bahareh Haddad; Bashkirova, Elizaveta; Melo, Sandra P; Wang, Pei; Leung, Thomas L; Siprashvili, Zurab; Tichy, Andrea; Li, Jiang; Ameen, Mohammed; Hawkins, John; Lee, Susie; Li, Lingjie; Schwertschkow, Aaron; Bauer, Gerhard; Lisowski, Leszek; Kay, Mark A; Kim, Seung K; Lane, Alfred T; Wernig, Marius; Oro, Anthony E

    2014-11-26

    Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We generated patient-derived COL7A1-corrected epithelial keratinocyte sheets for autologous grafting. We demonstrate the utility of sequential reprogramming and adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity, and these cells secreted wild-type type VII collagen, resulting in stratified epidermis in vitro in organotypic cultures and in vivo in mice. Sequencing of corrected cell lines before tissue formation revealed heterogeneity of cancer-predisposing mutations, allowing us to select COL7A1-corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB.

  3. Aminoglycosides restore full-length type VII collagen by overcoming premature termination codons: therapeutic implications for dystrophic epidermolysis bullosa.

    PubMed

    Cogan, Jon; Weinstein, Jacqueline; Wang, Xinyi; Hou, Yingping; Martin, Sabrina; South, Andrew P; Woodley, David T; Chen, Mei

    2014-10-01

    Patients with recessive dystrophic epidermolysis bullosa (RDEB) have severe, incurable skin fragility, blistering, and multiple skin wounds due to mutations in the gene encoding type VII collagen (C7), the major component of anchoring fibrils mediating epidermal-dermal adherence. Nearly 10-25% of RDEB patients carry nonsense mutations leading to premature stop codons (PTCs) that result in truncated C7. In this study, we evaluated the feasibility of using aminoglycosides to suppress PTCs and induce C7 expression in two RDEB keratinocyte cell lines (Q251X/Q251X and R578X/R906) and two primary RDEB fibroblasts (R578X/R578X and R163X/R1683X). Incubation of these cells with aminoglycosides (geneticin, gentamicin, and paromomycin) resulted in the synthesis and secretion of a full-length C7 in a dose-dependent and sustained manner. Importantly, aminoglycoside-induced C7 reversed the abnormal RDEB cell phenotype and incorporated into the dermal-epidermal junction of skin equivalents. We further demonstrated the general utility of aminoglycoside-mediated readthrough in 293 cells transiently transfected with expression vectors encoding 22 different RDEB nonsense mutations. This is the first study demonstrating that aminoglycosides can induce PTC readthrough and restore functional C7 in RDEB caused by nonsense mutations. Therefore, aminoglycosides may have therapeutic potential for RDEB patients and other inherited skin diseases caused by nonsense mutations.

  4. Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model.

    PubMed

    Wu, Wenbo; Lu, Zhiwei; Li, Fei; Wang, Wenjie; Qian, Nannan; Duan, Jinzhi; Zhang, Yu; Wang, Fengchao; Chen, Ting

    2017-02-14

    The prokaryotic CRISPR/Cas9 system has recently emerged as a powerful tool for genome editing in mammalian cells with the potential to bring curative therapies to patients with genetic diseases. However, efficient in vivo delivery of this genome editing machinery and indeed the very feasibility of using these techniques in vivo remain challenging for most tissue types. Here, we show that nonreplicable Cas9/sgRNA ribonucleoproteins can be used to correct genetic defects in skin stem cells of postnatal recessive dystrophic epidermolysis bullosa (RDEB) mice. We developed a method to locally deliver Cas9/sgRNA ribonucleoproteins into the skin of postnatal mice. This method results in rapid gene editing in epidermal stem cells. Using this method, we show that Cas9/sgRNA ribonucleoproteins efficiently excise exon80, which covers the point mutation in our RDEB mouse model, and thus restores the correct localization of the collagen VII protein in vivo. The skin blistering phenotype is also significantly ameliorated after treatment. This study provides an in vivo gene correction strategy using ribonucleoproteins as curative treatment for genetic diseases in skin and potentially in other somatic tissues.

  5. Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model

    PubMed Central

    Wu, Wenbo; Lu, Zhiwei; Li, Fei; Wang, Wenjie; Qian, Nannan; Duan, Jinzhi; Zhang, Yu; Wang, Fengchao; Chen, Ting

    2017-01-01

    The prokaryotic CRISPR/Cas9 system has recently emerged as a powerful tool for genome editing in mammalian cells with the potential to bring curative therapies to patients with genetic diseases. However, efficient in vivo delivery of this genome editing machinery and indeed the very feasibility of using these techniques in vivo remain challenging for most tissue types. Here, we show that nonreplicable Cas9/sgRNA ribonucleoproteins can be used to correct genetic defects in skin stem cells of postnatal recessive dystrophic epidermolysis bullosa (RDEB) mice. We developed a method to locally deliver Cas9/sgRNA ribonucleoproteins into the skin of postnatal mice. This method results in rapid gene editing in epidermal stem cells. Using this method, we show that Cas9/sgRNA ribonucleoproteins efficiently excise exon80, which covers the point mutation in our RDEB mouse model, and thus restores the correct localization of the collagen VII protein in vivo. The skin blistering phenotype is also significantly ameliorated after treatment. This study provides an in vivo gene correction strategy using ribonucleoproteins as curative treatment for genetic diseases in skin and potentially in other somatic tissues. PMID:28137859

  6. Identification of two rare and novel large deletions in ITGB4 gene causing epidermolysis bullosa with pyloric atresia.

    PubMed

    Mencía, Ángeles; García, Marta; García, Eva; Llames, Sara; Charlesworth, Alexandra; de Lucas, Raúl; Vicente, Asunción; Trujillo-Tiebas, María José; Coto, Pablo; Costa, Marta; Vera, Ángel; López-Pestaña, Arantxa; Murillas, Rodolfo; Meneguzzi, Guerrino; Jorcano, José Luis; Conti, Claudio J; Escámez Toledano, María José; del Río Nechaevsky, Marcela

    2016-04-01

    Epidermolysis bullosa with pyloric atresia (EB-PA) is a rare autosomal recessive hereditary disease with a variable prognosis from lethal to very mild. EB-PA is classified into Simplex form (EBS-PA: OMIM #612138) and Junctional form (JEB-PA: OMIM #226730), and it is caused by mutations in ITGA6, ITGB4 and PLEC genes. We report the analysis of six patients with EB-PA, including two dizygotic twins. Skin immunofluorescence epitope mapping was performed followed by PCR and direct sequencing of the ITGB4 gene. Two of the patients presented with non-lethal EB-PA associated with missense ITGB4 gene mutations. For the other four, early postnatal demise was associated with complete lack of β4 integrin due to a variety of ITGB4 novel mutations (2 large deletions, 1 splice-site mutation and 3 missense mutations). One of the deletions spanned 278 bp, being one of the largest reported to date for this gene. Remarkably, we also found for the first time a founder effect for one novel mutation in the ITGB4 gene. We have identified 6 novel mutations in the ITGB4 gene to be added to the mutation database. Our results reveal genotype-phenotype correlations that contribute to the molecular understanding of this heterogeneous disease, a pivotal issue for prognosis and for the development of novel evidence-based therapeutic options for EB management.

  7. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa

    PubMed Central

    Sebastiano, Vittorio; Zhen, Hanson Hui; Haddad, Bahareh; Bashkirova, Elizaveta; Melo, Sandra P.; Wang, Pei; Leung, Thomas L.; Siprashvili, Zurab; Tichy, Andrea; Li, Jiang; Ameen, Mohammed; Hawkins, John; Lee, Susie; Li, Lingjie; Schwertschkow, Aaron; Bauer, Gerhard; Lisowski, Leszek; Kay, Mark A.; Kim, Seung K.; Lane, Alfred T.; Wernig, Marius; Oro, Anthony E.

    2015-01-01

    Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We generated patient-derived COL7A1-corrected epithelial keratinocyte sheets for autologous grafting. We demonstrate the utility of sequential reprogramming and adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity, and these cells secreted wild-type type VII collagen, resulting in stratified epidermis in vitro in organotypic cultures and in vivo in mice. Sequencing of corrected cell lines before tissue formation revealed heterogeneity of cancer-predisposing mutations, allowing us to select COL7A1-corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB. PMID:25429056

  8. A novel KRT5 mutation associated with generalized severe epidermolysis bullosa simplex in a 2-year-old Chinese boy

    PubMed Central

    Zhang, Jia; Yan, Ming; Liang, Jianying; Li, Ming; Yao, Zhirong

    2016-01-01

    Mutations in keratin 5 (KRT5) or KRT14 genes are responsible for the most severe form of epidermolysis bullosa simplex (EBS), which is EBS generalized severe (EBS-gen sev). To date, only four pathogenic mutations (p.Arg165Ser and p.Lys199Asn in KRT5; p.Arg125Cys and p.Arg125His in KRT14) have been reported to be responsible for EBS-gen sev in the Chinese population. In the present study, a 2-year-old Chinese boy was clinically suspected to suffer from EBS, and thus Sanger sequencing was performed in the extracted genomic DNA samples from the patient, his parents and 100 healthy controls. A novel de novo heterozygous missense mutation c.503A>G (p.Glu168Gly) located at the N-terminal end segment of the 1A domain in KRT5 was identified by molecular analysis. In silico analysis tools were used to predict the pathogenicity of the novel missense mutation. A diagnosis of EBS-gen sev was thus confirmed according to the clinical presentations and molecular results. PMID:27882080

  9. Winter prevalence of obligate aphid pathogen Pandora neoaphidis mycosis in the host Myzus persicae populations in southern China: modeling description and biocontrol implication

    PubMed Central

    Zhou, Xiang

    2012-01-01

    Pandora neoaphidis overwintering had been investigated by monitoring its prevalence in Myzus persicae populations in open fields. Cabbage plants in field plots were weekly taken after mycosis initiation, to count and examine the living and dead aphids infected by P. neoaphidis . Based on the field data, infection levels ( I) varied with field temperature (T), relative humidity (RH) and aphid count (numbers of living aphids per plant, N) over days ( D), fitting well to the modified logistic equation I =0.91/[1+exp(8.5+(2.0 H T H RH-20.2 NI 0) D)] ( r 2=0.897), where H T indicated daily hours of low temperature (<4°C), H RH daily hours of high air humidity (>90% RH) and I 0 primary infection level. The model demonstrated the abiotic and biotic factors influencing P. neoaphidis mycosis development in winter, and also verifies the fungal overwintering by infecting available host aphids without a resting stage. Ultimately, P. neoaphidis mycosis reduced 81.4% of aphid populations, presenting great potential for biocontrol. PMID:24031835

  10. Winter prevalence of obligate aphid pathogen Pandora neoaphidis mycosis in the host Myzus persicae populations in southern China: modeling description and biocontrol implication.

    PubMed

    Zhou, Xiang

    2012-01-01

    Pandora neoaphidis overwintering had been investigated by monitoring its prevalence in Myzus persicae populations in open fields. Cabbage plants in field plots were weekly taken after mycosis initiation, to count and examine the living and dead aphids infected by P. neoaphidis . Based on the field data, infection levels ( I) varied with field temperature (T), relative humidity (RH) and aphid count (numbers of living aphids per plant, N) over days ( D), fitting well to the modified logistic equation I =0.91/[1+exp(8.5+(2.0 H T H RH-20.2 NI 0) D)] ( r (2)=0.897), where H T indicated daily hours of low temperature (<4°C), H RH daily hours of high air humidity (>90% RH) and I 0 primary infection level. The model demonstrated the abiotic and biotic factors influencing P. neoaphidis mycosis development in winter, and also verifies the fungal overwintering by infecting available host aphids without a resting stage. Ultimately, P. neoaphidis mycosis reduced 81.4% of aphid populations, presenting great potential for biocontrol.

  11. Sitobion avenae alatae infected by Pandora neoaphidis: their flight ability, post-flight colonization, and mycosis transmission to progeny colonies.

    PubMed

    Chen, Chun; Feng, Ming-Guang

    2004-07-01

    Epizootics caused by the obligate Entomophthorales pathogen Pandora neoaphidis may result from more than one possible means of fungal dissemination among host aphids, but we hypothesize that wide dispersal of the fungus is most likely to be associated with the flight behavior of migratory alates. We tested this hypothesis in a simulation experiment by assessing the flight capability of Sitobion avenae alates infected with P. neoaphidis and the potential of their post-flight survival, colonization, and mycosis transmission to progeny. A total of 281 alates were inoculated with P. neoaphidis, individually flown for up to 5h and 9km in a computer-monitored flight mill system and then reared for 10 days on wheat seedlings. The infected alates were capable of surviving on average for 2.9 days (range 1-7 days) and leaving 4.6 nymphs prior to deaths. Transmission of fungal infection within progeny colonies occurred after the mother alates died from P. neoaphidis mycosis. The level of contagious infection among the nymphs reached up to 16.8% within 7 days but varied with the survival time of the infected mother alates after flight. Based on stepwise polynomial regression analysis, progeny colony size was highly correlated with the interactions of flight time with both post-flight survival time and the number of nymphs left per alate before death (r2 = 0.997). Progeny mortality on day 5 after colonization was inversely correlated with post-flight survival time (r2 = 0.949) whereas infection on day 7 was correlated with flight distance and an interaction of post-flight survival time with fecundity of the infected alates (r2 = 0.970). Progeny mortality observed on day 10 was merely correlated to mortality observed on day 5 (r2 = 0.946). These results indicate a successful transmission of alate-borne P. neoaphidis to progeny colonies and further support our hypothesis on the means of primary dispersal of aphid epizootics by migratory alates in a geographically wide range.

  12. Comparison of 3 type VII collagen (C7) assays for serologic diagnosis of epidermolysis bullosa acquisita (EBA).

    PubMed

    Seta, Vannina; Aucouturier, Françoise; Bonnefoy, Jonathan; Le Roux-Villet, Christelle; Pendaries, Valérie; Alexandre, Marina; Grootenboer-Mignot, Sabine; Heller, Michel; Lièvre, Nicole; Laroche, Liliane; Caux, Frédéric; Titeux, Matthias; Hovnanian, Alain; Prost-Squarcioni, Catherine

    2016-06-01

    Serologic diagnosis of epidermolysis bullosa acquisita (EBA) relies on the detection of circulating autoantibodies to type VII collagen (C7). We sought to compare the diagnostic performances of a commercialized enzyme-linked immunosorbent assay (ELISA) using C7 noncollagenous (NC) domains (C7-NC1/NC2 ELISA) and indirect immunofluorescence (IIF) biochip test on NC1-C7-expressing transfected cells (IIFT), with a full-length-C7 ELISA developed in our laboratory. C7-NC1/NC2 ELISA, IIFT, and full-length-C7 ELISA were run on 77 nonselected consecutive EBA sera. C7-NC1/NC2 ELISA, IIFT, and full-length-C7 ELISA were positive, respectively, for: 30%, 27%, and 65% of the 77 sera; 43%, 32%, and 80% of 44 sera labeling the salt-split-skin (SSS) floor (F) by IIF (SSS/F(+)); 9%, 22%, and 47% of 32 SSS/F(-) sera; 28%, 28%, and 58% of classic EBA; 41%, 41%, and 82% of inflammatory EBA; and 18%, 0%, and 55% of mucous-membrane-predominant EBA. Significant differences for all sera were found between: the 2 ELISAs for the 77 sera, SSS/F(+) and SSS/F(-) sera, and IIFT versus full-length-C7 ELISA. The retrospective design was a limitation. C7-NC1/NC2 ELISA and IIFT sensitivities for serologic diagnoses of EBA were low. Full-length-C7 ELISA was significantly more sensitive and could serve as a reference test. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  13. Recurrent nonsense mutations within the type VII collagen gene in patients with severe recessive dystrophic epidermolysis bullosa

    SciTech Connect

    Hovnanian, A.; Hilal, L.; Goossens, M. ); Blanchet-Bardon, C.; Prost, Y. de ); Christiano, A.M.; Uitto, J. )

    1994-08-01

    The generalized mutilating form of recessive dystrophic epidermolysis bullosa (i.e., the Hallopeau-Siemens type; HS-RDEB) is a life-threatening disease characterized by extreme mucocutaneous fragility associated with absent or markedly altered anchoring fibrils (AF). Recently, the authors reported linkage between HS-RDEB and the type VII collagen gene (COL7A1), which encodes the major component of AF. In this study, they investigated 52 unrelated HS-RDEB patients and 2 patients with RDEB inversa for the presence, at CpG dinucleotides, of mutations changing CGA arginine codons to premature stop codons TGA within the COL7A1 gene. Eight exons containing 10 CGA codons located in the amino-terminal domain of the COL7A1 gene were studied. Mutation analysis was performed using denaturing gradient gel electrophoresis of PCR-amplified genomic fragments. Direct sequencing of PCR-amplified products with altered electrophoretic mobility led to the characterization of three premature stop codons, each in a single COL7A1 allele, in four patients. Two patients (one affected with HS-RDEB and the other with RDEB inversa) have the same C-to-T transition at arginine codon 109. Two other HS-RDEB patients have a C-to-T transition at arginine 1213 and 1216, respectively. These nonsense mutations predict the truncation of [approximately]56%-92% of the polypeptide, including the collagenous and the noncollagenous NC-2 domains. On the basis of linkage analysis, which showed no evidence for locus heterogeneity in RDEB, it is expected that these patients are compound heterozygotes and have additional mutations on the other COL7A1 allele, leading to impaired AF formation. These results indicate that stop mutations within the COL7A1 gene can underlie both HS-RDEB and RDEB inversa, thus providing further evidence for the implication of this gene in RDEB. 46 refs., 3 figs., 1 tab.

  14. Using immunofluorescence (antigen) mapping in the diagnosis and classification of epidermolysis bullosa: a first report from Iran.

    PubMed

    Barzegar, Mohammadreza; Asadi-Kani, Zahra; Mozafari, Nikoo; Vahidnezhad, Hassan; Kariminejad, Ariana; Toossi, Parviz

    2015-10-01

    Immunofluorescence antigen mapping (IFM), is a newly introduced technique for diagnosis and classification of epidermolysis bullosa (EB) disease. The precise level of skin cleavage can be determined using monoclonal antibodies to EB-specific basement membrane zone protein. To apply IFM technique in diagnosis and classification of EB and to identify utility and limitation of this method in our clinical setting. IFM was done according to a described protocol by Pohla-Gubo et al. Monoclonal antibodies used for antigen mapping were against cytokeratin 5, cytokeratin 14, α6 integrin, β4 integrin, laminin 332, Collagen IV, and Collagen VII. IFM was done for 95 referred patients, compromising 49 females and 46 males, aged 5 days to 45 years (mean = 9.5 years). Ninety cases were diagnosed with EB and classified as follows: EB simplex: (n = 13), junctional EB (n = 14), dystrophic EB (n = 62), and Kindler syndrome (n = 1). Diagnosis was not made in five cases as their specimens contained no blister. Confirmatory genetic analysis was done for five junctional cases from two families with clinical features of laryngo-onycho-cutaneous syndrome. Genetic molecular studies showed nonsense mutations in the last codon of exon 39 of the laminin α3a (LAMA3) gene (p.Gln57X) and a donor splice site mutation in LAMA3 (IVS57+5G>A) in the first and second family, respectively. IFM technique is relatively simple to perform, and interpretation of the results is not sophisticated. The proportion of inconclusive results will be decreased if the specimens contain freshly induced blister. © 2015 The International Society of Dermatology.

  15. Social/economic costs and health-related quality of life in patients with epidermolysis bullosa in Europe.

    PubMed

    Angelis, Aris; Kanavos, Panos; López-Bastida, Julio; Linertová, Renata; Oliva-Moreno, Juan; Serrano-Aguilar, Pedro; Posada-de-la-Paz, Manuel; Taruscio, Domenica; Schieppati, Arrigo; Iskrov, Georgi; Brodszky, Valentin; von der Schulenburg, Johann Matthias Graf; Chevreul, Karine; Persson, Ulf; Fattore, Giovanni

    2016-04-01

    The aim of this study was to determine the social/economic costs and health-related quality of life (HRQOL) of patients with epidermolysis bullosa (EB) in eight EU member states. We conducted a cross-sectional study of patients with EB from Bulgaria, France, Germany, Hungary, Italy, Spain, Sweden and the United Kingdom. Data on demographic characteristics, health resource utilisation, informal care, labour productivity losses, and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. A total of 204 patients completed the questionnaire. Average annual costs varied from country to country, and ranged from €9509 to €49,233 (reference year 2012). Estimated direct healthcare costs ranged from €419 to €10,688; direct non-healthcare costs ranged from €7449 to €37,451 and labour productivity losses ranged from €0 to €7259. The average annual cost per patient across all countries was estimated at €31,390, out of which €5646 accounted for direct health costs (18.0 %), €23,483 accounted for direct non-healthcare costs (74.8 %), and €2261 accounted for indirect costs (7.2 %). Costs were shown to vary across patients with different disability but also between children and adults. The mean EQ-5D score for adult EB patients was estimated at between 0.49 and 0.71 and the mean EQ-5D visual analogue scale score was estimated at between 62 and 77. In addition to its negative impact on patient HRQOL, our study indicates the substantial social/economic burden of EB in Europe, attributable mostly to high direct non-healthcare costs.

  16. Transplanted bone marrow-derived circulating PDGFRα+ cells restore type VII collagen in recessive dystrophic epidermolysis bullosa mouse skin graft.

    PubMed

    Iinuma, Shin; Aikawa, Eriko; Tamai, Katsuto; Fujita, Ryo; Kikuchi, Yasushi; Chino, Takenao; Kikuta, Junichi; McGrath, John A; Uitto, Jouni; Ishii, Masaru; Iizuka, Hajime; Kaneda, Yasufumi

    2015-02-15

    Recessive dystrophic epidermolysis bullosa (RDEB) is an intractable genetic blistering skin disease in which the epithelial structure easily separates from the underlying dermis because of genetic loss of functional type VII collagen (Col7) in the cutaneous basement membrane zone. Recent studies have demonstrated that allogeneic bone marrow transplantation (BMT) ameliorates the skin blistering phenotype of RDEB patients by restoring Col7. However, the exact therapeutic mechanism of BMT in RDEB remains unclear. In this study, we investigated the roles of transplanted bone marrow-derived circulating mesenchymal cells in RDEB (Col7-null) mice. In wild-type mice with prior GFP-BMT after lethal irradiation, lineage-negative/GFP-positive (Lin(-)/GFP(+)) cells, including platelet-derived growth factor receptor α-positive (PDGFRα(+)) mesenchymal cells, specifically migrated to skin grafts from RDEB mice and expressed Col7. Vascular endothelial cells and follicular keratinocytes in the deep dermis of the skin grafts expressed SDF-1α, and the bone marrow-derived PDGFRα(+) cells expressed CXCR4 on their surface. Systemic administration of the CXCR4 antagonist AMD3100 markedly decreased the migration of bone marrow-derived PDGFRα(+) cells into the skin graft, resulting in persistent epidermal detachment with massive necrosis and inflammation in the skin graft of RDEB mice; without AMD3100 administration, Col7 was significantly supplemented to ameliorate the pathogenic blistering phenotype. Collectively, these data suggest that the SDF1α/CXCR4 signaling axis induces transplanted bone marrow-derived circulating PDGFRα(+) mesenchymal cells to migrate and supply functional Col7 to regenerate RDEB skin.

  17. Immunogenicity of Decidual Stromal Cells in an Epidermolysis Bullosa Patient and in Allogeneic Hematopoietic Stem Cell Transplantation Patients

    PubMed Central

    Carlson, Lena-Maria; Erkers, Tom; Nava, Silvia; Molldén, Pia; Gustafsson, Britt; Qian, Hua; Li, Xiaoguang; Hashimoto, Takashi; Sadeghi, Behnam; Alheim, Mats; Ringdén, Olle

    2015-01-01

    Allogeneic mesenchymal stromal cells (MSCs) are widely used in regenerative medicine, but little is known about their immunogenicity. In this study, we monitored the therapeutic and immunogenic effects of decidual stromal cells (DSCs) from term placentas when used as a therapy for generalized severe junctional epidermolysis bullosa (JEB) (previously termed Herlitz JEB), a lethal condition caused by the lack of functional laminin-332. An 11-month-old JEB patient was treated with five infusions of allogeneic DSCs within a 3-month period. Amniotic membranes (AMs) were applied to severe wounds. After the treatment, wounds started to heal in the middle of the blisters, but the improvements were transient. After two infusions of DSCs, the JEB patient had developed multispecific anti-HLA class-I antibodies. No antibodies to laminin-332 were detected, but the patient had high levels of anti-bovine serum albumin antibodies, which could bind to DSCs. Peripheral blood mononuclear cells (PBMCs) from the patient had a higher proliferative response to DSCs than to third-party PBMCs, which contrasts with the pattern observed in healthy donors. Human DSCs and MSCs induced similar xenoreactivity in mice. Two of 16 allogeneic stem cell-transplanted patients, treated with DSCs for graft-versus-host disease or hemorrhagic cystitis, showed a positive flow cytometric crossmatch test. One patient had anti-HLA antibodies before DSC infusion, whereas the other had no anti-HLA antibodies at any time. AM and DSC infusions may have improved the healing process in the JEB patient, but DSCs appeared to induce anti-HLA antibodies. The risk of alloimmunization by DSCs seems to be low in immunocompromised patients. PMID:25658253

  18. Higher Dental Caries Prevalence and Its Association with Dietary Habits and Physical Limitation in Epidermolysis Bullosa Patients: A Case Control Study.

    PubMed

    Leal, Soraya Coelho; Lia, Erica Negrini; Amorim, Rivadavio; Dos Santos, Mateus Veppo; de Araújo, Mayara Cundari; de Medeiros, Rodrigo Antônio; da Fonseca, Camila Abdanur

    2016-03-01

    Epidermolysis bullosa (EB) represents a highly rare subgroup of skin diseases that affects skin and mucous membrane. The aim of the present study was to assess caries prevalence and its associated factors in EB subjects. Salivary status was also assessed. Ten subjects with EB who were under supervision were selected (cases) and matched by age and gender with unaffected individuals (controls). Dental caries were recorded using the World Health Organization (WHO) criteria. Oral hygiene and dietary habits were investigated by clinical examination and questionnaires. Both nonstimulated and stimulated saliva were collected and salivary pH, buffering capacity and mouth opening were evaluated. The results showed that the median decay-missing-filled teeth was significantly higher (p = 0.0094) in EB cases 5 (3.9-20.3) than in controls 3 (2-3.25). The groups also differed when food consistency was analyzed. Individuals with EB have a higher intake of soft food. In addition, the median mouth-opening values from cases (0.84-2.84 cm) and controls (4.3-4.9 cm) have shown to be statistically different (p = 0.007). Considering the salivary parameters, none of them showed significant differences among groups. Epidermolysis bullosa subjects present higher caries scores and might be related to their physical condition and dietary habits. There is a lack of information about oral status in EB subjects. Hence, our findings add useful information regarding the relationship between caries prevalence and associated risk factors in EB subjects.

  19. Epidermolysis Bullosa Simplex-Type Mutations Alter the Dynamics of the Keratin Cytoskeleton and Reveal a Contribution of Actin to the Transport of Keratin SubunitsD⃞V⃞

    PubMed Central

    Werner, Nicola Susann; Windoffer, Reinhard; Strnad, Pavel; Grund, Christine; Leube, Rudolf Eberhard; Magin, Thomas Michael

    2004-01-01

    Dominant keratin mutations cause epidermolysis bullosa simplex by transforming keratin (K) filaments into aggregates. As a first step toward understanding the properties of mutant keratins in vivo, we stably transfected epithelial cells with an enhanced yellow fluorescent protein-tagged K14R125C mutant. K14R125C became localized as aggregates in the cell periphery and incorporated into perinuclear keratin filaments. Unexpectedly, keratin aggregates were in dynamic equilibrium with soluble subunits at a half-life time of <15 min, whereas filaments were extremely static. Therefore, this dominant-negative mutation acts by altering cytoskeletal dynamics and solubility. Unlike previously postulated, the dominance of mutations is limited and strictly depends on the ratio of mutant to wild-type protein. In support, K14R125C-specific RNA interference experiments resulted in a rapid disintegration of aggregates and restored normal filaments. Most importantly, live cell inhibitor studies revealed that the granules are transported from the cell periphery inwards in an actin-, but not microtubule-based manner. The peripheral granule zone may define a region in which keratin precursors are incorporated into existing filaments. Collectively, our data have uncovered the transient nature of keratin aggregates in cells and offer a rationale for the treatment of epidermolysis bullosa simplex by using short interfering RNAs. PMID:14668478

  20. Studies on Local Immunosuppression in Skin Grafting.

    DTIC Science & Technology

    These malignant diseases in man included malignant melanoma, Kaposi ’ hemorrhagic sarcoma , adrenocarcinoma of the breast, epidermoid carcinoma of...the lower female genitourinary tract, mycosis fungoides, and reticulum cell sarcoma . Previous findings of the feasibility and clinical effectiveness of