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Sample records for mycosis fungoides bullosa

  1. Unusual variants of mycosis fungoides.

    PubMed

    Abeldaño, Alejandra; Arias, Mariana; Benedetti, Adriana; Ochoa, Karina; Maskin, Matías; Pellerano, Graciela; Kien, María Cristina; Chouela, Edgardo

    2011-01-01

    Unusual variants of mycosis fungoides (MF) differ substantially from the classical presentation, and most of them resemble other dermatologic diseases. The authors reviewed files of patients with MF who consulted our clinic between November 1995 and June 2010 to evaluate the relative frequency and clinical behavior of these variants. Among 98 patients with MF, 32 (32.65%) had unusual variants. The most common types included follicular MF (31.25%), hypopigmented MF (18.75%), poiquilodermic MF (15.6%), and erythrodermic MF (12.5%). Less common variants included unilesional MF, bullosa MF, ichthyosiform MF, granulomatous slack skin, and pigmented purpura-like MF. Progressive disease and MF-related death were most commonly associated with follicular MF, bullosa MF, and erythrodermic MF. PMID:21980706

  2. Phototherapy of Mycosis Fungoides.

    PubMed

    Hodak, Emmilia; Pavlovsky, Lev

    2015-10-01

    Therapies based on ultraviolet light have long been established in mycosis fungoides (MF). They have traditionally included whole-body ultraviolet light B, both broad-band and narrow-band, and psoralen plus ultraviolet A. Phototherapy may be applied alone in early stage MF or in combination with systemic therapy in refractory early stage MF and advanced MF. This article reviews the most frequently used forms of phototherapy for MF with emphasis on efficacy, safety, and practical considerations. PMID:26433842

  3. Mycosis fungoides: classic disease and variant presentations.

    PubMed

    Howard, M S; Smoller, B R

    2000-06-01

    Mycosis fungoides is a peripheral non-Hodgkin's T-cell neoplastic process, representing the most common type of primary cutaneous malignant lymphoma. Neoplastic lesions classically show skin predilection and characteristic clinical and histologic features in patch, plaque, and tumor stages. In addition, several clinicopathologic variants of mycosis fungoides have been delineated, including poikiloderma atrophicans vasculare (parapsoriasis variegata), Sézary syndrome, granulomatous mycosis fungoides, hypopigmented mycosis fungoides, folliculocentric mycosis fungoides, syringotropic mycosis fungoides, and Woringer Kolopp disease. We will review the salient features of patch, plaque, and tumor stage mycosis fungoides in this article and follow with a discussion of these variant clinicopathologic presentations and of therapeutic modalities. PMID:10892710

  4. Mycosis Fungoides Variants.

    PubMed

    Martínez-Escala, M Estela; González, Belén Rubio; Guitart, Joan

    2014-06-01

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that usually manifests as patches and plaques with a propensity for nonphotoexposed areas. MF is a common mimicker of inflammatory and infectious skin diseases, because it can be manifested with a wide variety of clinical and pathologic presentations. These atypical presentations of MF may be difficult to diagnose, requiring a high level of suspicion and careful clinicopathologic correlation. Within this array of clinical presentations, the World Health Organization classification recognizes 3 MF variants: folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin. These 3 variants, as well as hypopigmented MF, are addressed in this article. PMID:26837197

  5. "Hypopigmented mycosis fungoides" is not always mycosis fungoides!

    PubMed

    Werner, Betina; Brown, Sonya; Ackerman, A Bernard

    2005-02-01

    We conducted a critical review of hypopigmented mycosis fungoides in historical perspective with emphasis on criteria clinical and histopathologic for diagnosis of that lymphoma as they are set forth in every article ever written about it. Toward that end, we undertook analysis of each article in the medical literature that mentioned hypopigmentation in mycosis fungoides (34 in toto). Each was scrutinized regarding content, photographs of lesions clinical pictured, and photomicrographs. On the basis of all the information in the 34 publications available to us, we made a determination about which patients had mycosis fungoides without doubt, which surely did not, and which about whom no judgment could be made by us because too little data requisite for such a decision was provided, especially in terms of photographs of lesions clinical and of photomicrographs. To date, 106 patients with "hypopigmented mycosis fungoides" have been reported on. Features clinical and findings histopathologic in 23 of those 106 patients were sufficient to permit us to determine, with a high degree of confidence, whether or not a particular patient truly had mycosis fungoides. In our judgment, 19 patients did have mycosis fungoides, whereas at least four patients did not. In regard to the other 83 patients, the information provided by the authors simply was not sufficient to allow us to come to a decision that we could justify. PMID:15677981

  6. Genetics Home Reference: mycosis fungoides

    MedlinePlus

    ... such as environmental exposure or certain bacterial or viral infections, are involved in the development of mycosis fungoides . ... behaviors. Blood. 2010 Aug 5;116(5):767-71. doi: 10.1182/blood-2009-11-251926. Epub ...

  7. Hypopigmented mycosis fungoides in childhood and adolescence.

    PubMed

    Neuhaus, I M; Ramos-Caro, F A; Hassanein, A M

    2000-01-01

    We present a case of purely hypopigmented mycosis fungoides of 8-years duration in an 18-year-old woman who responded readily to psoralen plus ultraviolet A (PUVA) treatment. The literature pertaining to hypopigmented mycosis fungoides is reviewed. PMID:11085673

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

    ClinicalTrials.gov

    2016-07-21

    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

  9. Mycosis fungoides presenting as pigmented purpuric dermatitis.

    PubMed

    Hanna, Shannon; Walsh, Noreen; D'Intino, Yolanda; Langley, Richard G B

    2006-01-01

    Mycosis fungoides, a cutaneous T-cell lymphoma, typically presents as indolent, progressive, and persistent erythematous patches or plaques with mild scaling and over time can evolve into tumor stage with tumor nodules. Other presentations include eczematous, psoriasiform, poikilodermatous, and hypopigmented patches. We report Mycosis fungoides in a 14-year-old boy presenting as pigmented purpuric dermatitis and review the relevant literature. This is a rare presentation of a condition that is uncommon in the pediatric population. In our patient, histologic features were typical of Mycosis fungoides presenting as pigmented purpuric dermatitis. The clinical features, pathology, molecular biology, and the relationship between these two entities are discussed. PMID:16918631

  10. Hypopigmented mycosis fungoides treated successfully with puva.

    PubMed

    Khanna, N; Dogra, D; Manchanda, Y; Singh, M K

    1999-01-01

    Hypopigmented lesions are rarely encountered in mycosis fungoides. We here report a 22-year old female patient who presented with a 5-year history of asymptomatic progressively increasing discrete and confluent hypopigmented macules and a 1-year history of a few itchy erythematous, scaly, indurated plaques. The histological features were consistent with a clinical diagnosis of mycosis fungoides. She was successfully treated with PUVA therapy. PMID:20921689

  11. Immunotactoid glomerulopathy associated with mycosis fungoides.

    PubMed Central

    Torrelo, A.; Rivera, M. T.; Mampaso, F.; España, A.; Marcèn, R.; Ortuño, J.; Ledo, A.

    1990-01-01

    A patient with mycosis fungoides developed a nephrotic syndrome. Renal biopsy revealed deposits of a highly organized fibrillar material which did not stain with the typical amyloid stains; this picture was consistent with the diagnosis of non-amyloidotic fibrillary glomerulopathy or immunotactoid glomerulopathy. We believe this is the first case reported of immunotactoid glomerulopathy associated with mycosis fungoides. Possible pathogenetic implications are discussed with reference to previous publications. Images Figure 1 Figure 2 PMID:2235815

  12. Koebner Phenomenon and Mycosis Fungoides

    PubMed Central

    Lebas, Eve; Libon, Florence; Nikkels, Arjen F.

    2015-01-01

    Mycosis fungoides (MF) is the most frequent type of primary cutaneous T-cell/NK-cell lymphoma. The Koebner phenomenon is defined as the appearance of cutaneous lesions on previously noninvolved skin following trauma and is observed in a series of cutaneous diseases including psoriasis, lichen planus, viral warts, molluscum contagiosum, etc. In this case report, 3 patients with longstanding MF are presented, the 1st with the appearance of a circumscribed early-stage type MF lesion rapidly following a surgical excision of an infundibular cyst, the 2nd with the appearance of a unique unilateral palmar tumoral MF lesion at the pressure site of a crutch, and the 3rd presented localized MF early stage lesions at the friction site of a belt. This report suggests that some MF patients may experience Koebner phenomenon-induced MF lesions and that MF should be added to the long list of skin diseases potentially exhibiting the Koebner phenomenon. PMID:26557075

  13. ELECTRON BEAM THERAPY OF MYCOSIS FUNGOIDES

    PubMed Central

    Bagshaw, Malcolm A.; Schneidman, Harold M.; Farber, Eugene M.; Kaplan, Henry S.

    1961-01-01

    Ionizing radiation in the form of x-ray therapy is the best modality of treatment available at the present time for single, isolated lesions of mycosis fungoides. However, for generalized mycosis fungoides, generalized x-ray therapy is technically difficult and dangerous. It is now possible to employ electron beam therapy for generalized mycosis fungoides, using energies which confine the dose to the superficial layers of the skin and thus avoid hematopoietic injury. A technique for wide field electron beam therapy has been developed for this purpose which has been effective and well tolerated in limited trials to date. ImagesFigure 2.Figure 4.Figure 4.Figure 4.Figure 5.Figure 5.Figure 5.Figure 6. AFigure 6. A PMID:13863947

  14. Minimal residual disease in hypopigmented mycosis fungoides.

    PubMed

    Hsiao, Pa-Fan; Hsiao, Cheng-Hsiang; Tsai, Tsen-Fang; Jee, Shiou-Hwa

    2006-05-01

    We describe the case of a 13-year-old boy with stage I hypopigmented mycosis fungoides in whom minimal residual disease was detected with T-cell receptor gamma-polymerase chain reaction after the disease was in complete clinical remission. We further cloned and sequenced the T-cell receptor gamma-polymerase chain reaction product of the lesion in remission and found that the original T-cell clone still existed in decreased amounts. The patient was followed up for 3 1/2 years without any new lesions developing. The clinical significance of this residual malignant T-cell clone in mycosis fungoides remains to be elucidated. PMID:16631939

  15. 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

  16. A case of hypopigmented mycosis fungoides.

    PubMed

    Choe, Y B; Park, K C; Cho, K H

    2000-08-01

    We experienced a 26-year-old woman in whom widespread hypopigmented macules and patches developed as the initial clinical feature of mycosis fungoides. Histopathological examination confirmed the diagnosis. The patients was treated with PUVA, and the lesion progressively disappeared within five months. PMID:10989581

  17. Hypopigmented mycosis fungoides associated with atopy in two children.

    PubMed

    Onsun, N; Kural, Y; Su, O; Demirkesen, C; Büyükbabani, N

    2006-01-01

    Mycosis fungoides is very rare in children. Hypopigmented lesions of this disease are usually observed in dark-skinned individuals and often show a T supressor CD8(+) phenotype. Two Caucasian children with predominantly hypopigmented lesions of mycosis fungoides are presented here. Atopy was a concomitant feature in both. PMID:17014650

  18. Free-floating collagen fibers in interstitial mycosis fungoides.

    PubMed

    Ferrara, Gerardo; Crisman, Giuliana; Zalaudek, Iris; Argenziano, Giuseppe; Stefanato, Catherine M

    2010-06-01

    We present a case of interstitial mycosis fungoides showing pseudodovascular clefts with "free-floating" collagen fibers surrounded by neoplastic T lymphocytes. Such a finding further expands the histopathologic spectrum of mycosis fungoides and could be taken into account in its differential diagnosis from granuloma annulare, inflammatory morphea, and interstitial granulomatous drug reaction. PMID:20145533

  19. Mycosis Fungoides: Case Report and Literature Review

    PubMed Central

    Akinbami, Akinsegun A; Osikomaiya, Bodunrin I; John-Olabode, Sarah O; Adediran, Adewumi A; Osinaike, Olajumoke; Uche, Ebele I; Ismail, Ayobami K; Dosunmu, Adedoyin O; Odesanya, Mojeed; Dada, Akinola; Okunoye, Olaitan

    2014-01-01

    Mycosis fungoides (MF), also known as Alibert-Bazin syndrome or granuloma fungoides, is the most common form of cutaneous T-cell lymphoma. Cutaneous lymphomas are an uncommon, heterogeneous group of non-Hodgkin lymphomas (NHLs) of T- and B-cell origin where the skin is the primary organ of involvement. This is a case of a 60-year-old Nigerian woman, who was diagnosed and managed as a case of chronic dermatitis but further investigations confirmed a diagnosis of MF; she was thereafter managed with topical glucocorticoids/chemotherapy and improved on these treatments. We make a plea for better awareness of the disease among physicians and pathologists in Africa. PMID:25232282

  20. 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

  1. Mycosis fungoides with unusual vitiligo-like presentation.

    PubMed

    Das, Jayanta Kumar; Gangopadhyay, Asok Kumar

    2004-01-01

    Mycosis fungoides (MF), the commonest variant of primary cutaneous T cell lymphoma (CTCL), is relatively uncommon among the Asians. Hypopigmented mycosis fungoides is a rare variant usually observed in dark-skinned individuals, especially children. Hypopigmented MF usually responds well to therapy, particularly to PUVA, and has a comparatively benign course. Mycosis fungoides in a 16-year-old boy, with extensive asymptomatic hypopigmented lesions developing gradually all over the body over eight years and vitiligo-like skin lesions developing for seven years, with no systemic features, is presented for its unusual clinical features and conspicuous histopathological findings of prominent epidermotropism. The case showed fairly good response to PUVASOL therapy. PMID:17642645

  2. Allogeneic hematopoietic stem cell transplantation in mycosis fungoides*

    PubMed Central

    Atalla, Angelo; Hallack Neto, Abrahão Elias; Siqueira, Denise Bittencourt; Toledo, Gabriela Cumani

    2013-01-01

    Mycosis Fungoides is typically an indolent disease in early stages. However, approximately 30% of patients have advanced staged disease at presentation and 20% will develop it at some time. These patients have a poorer prognosis with a median survival of 2-4 years. The only curative option for mycosis fungoides may be hematopoietic allogeneic stem cell transplantation. We report the case of a patient with mycosis fungoides in an advanced stage (IIB), refractory to treatment options. She underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The patient remains in complete remission nineteen months after allo-HSCT. Allogeneic transplantation can alter the natural history of mycosis fungoides and should be considered in patients who have refractory disease or short-lived responses with standard therapies. PMID:24346924

  3. Pigmented purpuric dermatosis or mycosis fungoides: A diagnostic dilemma.

    PubMed

    Riyaz, Najeeba; Sasidharanpillai, Sarita; Abdul Latheef, Ettappurath N; Davul, Hena; Ashraf, Febin

    2016-01-01

    Pigmented purpuric dermatoses (PPD), a group of vascular disorders with variable clinical picture is reported in all races and age groups with a male predilection. There are reports of mycosis fungoides manifesting as pigmented purpura as well as progression of PPD to cutaneous T-cell lymphoma. The diagnostic dilemma is compounded by PPD manifesting histological similarity to mycosis fungoides. Currently, it is believed that PPD with monoclonal T-cell population is more likely to progress to malignancy. We report a 31-year-old male patient who presented with the lichenoid clinical variant of PPD lesions that mimicked mycosis fungoides on histopathology. Gene rearrangement studies identified a polyclonal T-cell population. The patient responded to photochemotherapy, which is beneficial in both PPD and mycosis fungoides. Our case signifies the limitations of current diagnostic modalities in accurately distinguishing PPD from cutaneous lymphoma. Data on disease progression in similar cases may enable us to formulate better diagnostic definitions. PMID:27294054

  4. Pigmented purpuric dermatosis or mycosis fungoides: A diagnostic dilemma

    PubMed Central

    Riyaz, Najeeba; Sasidharanpillai, Sarita; Abdul Latheef, Ettappurath N.; Davul, Hena; Ashraf, Febin

    2016-01-01

    Pigmented purpuric dermatoses (PPD), a group of vascular disorders with variable clinical picture is reported in all races and age groups with a male predilection. There are reports of mycosis fungoides manifesting as pigmented purpura as well as progression of PPD to cutaneous T-cell lymphoma. The diagnostic dilemma is compounded by PPD manifesting histological similarity to mycosis fungoides. Currently, it is believed that PPD with monoclonal T-cell population is more likely to progress to malignancy. We report a 31-year-old male patient who presented with the lichenoid clinical variant of PPD lesions that mimicked mycosis fungoides on histopathology. Gene rearrangement studies identified a polyclonal T-cell population. The patient responded to photochemotherapy, which is beneficial in both PPD and mycosis fungoides. Our case signifies the limitations of current diagnostic modalities in accurately distinguishing PPD from cutaneous lymphoma. Data on disease progression in similar cases may enable us to formulate better diagnostic definitions. PMID:27294054

  5. Intraocular involvement with subretinal pigment epithelium infiltrates by mycosis fungoides.

    PubMed Central

    Erny, B. C.; Egbert, P. R.; Peat, I. M.; Shorrock, K.; Rosenthal, A. R.

    1991-01-01

    We report a case of intraocular mycosis fungoides in a 48-year-old man. The patient presented with decreased visual acuity, white subretinal lesions, and vitritis. Post-mortem histopathology revealed malignant T cell infiltrates consistent with mycosis fungoides in the retina, vitreous, and between the retinal pigment epithelium (RPE) and Bruch's membrane Focal atrophy of the RPE, along with the sub-RPE infiltrates, correlated with the clinically visible fundus lesions. Images PMID:1751471

  6. A Case of Mycosis Fungoides and Lymphomatoid Papulosis Occurring Simultaneously in a Child

    PubMed Central

    Bognet, Rachel A.; Kozic, Heidi; Lee, Jason B.; Sahu, Joya; Hyde, Patrice M.

    2012-01-01

    Several studies have reported an association between lymphomatoid papulosis and other lymphomas, such as mycosis fungoides, Hodgkin’s disease, and anaplastic large cell lymphoma. The association between lymphomatoid papulosis and mycosis fungoides has been reported to be between seven and 39 percent. Although a relationship is acknowledged between lymphomatoid papulosis and mycosis fungoides, our understanding is limited. The authors report a case of mycosis fungoides and lymphomatoid papulosis in a child. PMID:23198014

  7. [Interstitial mycosis fungoid: a rare variant of mycosis fungoids. Two cases].

    PubMed

    Paoletti, Marie-Thérèse; Comoz, François; Dompmartin-Blanchere, Anne; Bagot, Martine; Ortonne, Nicolas

    2011-02-01

    Mycosis fungoids can present with various clinical and histological features, with only a few of them being recognized as distinct entities in the current WHO and EORTC classifications. Histologically, mycosis fungoids (MF) usually show a superficial perivascular or band-like lymphocytic infiltrate with epidermotropism. We here report two cases of a rare histological variant of MF, called interstitial in the literature. Our first patient, a 71-year-old male, had a previously diagnosed MF, which clinically evolved towards nodules, showing histologically an interstitial lymphocytic infiltrate without epidermotropism and without large cell transformation. The second patient was a 64-year-old female with widespread plaques and nodules. Histologically, a dense dermal interstitial infiltrate was observed, with foci of epidermotropism, without large cell transformation. At relapse after treatment, she presented with plaques, papules and nodules, histologically showing a slight interstitial lymphocytic infiltrate that resembled granuloma annulare or inflammatory morphea. In both patients, clinical aspect suggested MF and a dominant T-cell clone was found in lesional skin. Nodules in MF are not always the hallmark of large cell transformation, but may correspond to unusual interstitial lesions. Diagnosis of such rare variant may be difficult and requires a good clinical pathological correlation together with the search for foci of epidermotropism on skin biopsy and for a dominant cutaneous T-cell clone. PMID:21349387

  8. Mycosis fungoides with a CD56+ immunophenotype.

    PubMed

    Wain, E Mary; Orchard, Guy E; Mayou, Susan; Atherton, David J; Misch, Klaus J; Russell-Jones, Robin

    2005-07-01

    We report 3 cases of mycosis fungoides (MF) with a CD56+ cytotoxic immunophenotype. Each patient presented with a different clinical phenotype: one exhibited limited poikilodermatous patches (skin stage T1); one, widespread hypopigmented lesions (skin stage T2); and one, poikiloderma with a single cutaneous tumor (skin stage T3). MF was confirmed both histologically and by the presence of a T-cell receptor clone in lesional skin in all cases. CD56 and T-cell intracellular antigen-1 were expressed by the malignant lymphocytes in all patients and two expressed CD8. No sample demonstrated loss of the pan T-cell markers CD2 or CD3. None of the 3 developed systemic disease and T-cell receptor gene analysis of peripheral blood was polyclonal in all cases. Only 3 cases of CD56+ MF have been reported previously, none of which exhibited tumor-stage disease. Currently, the disease in our patients appears to be behaving in a manner similar to that predicted for MF with a normal immunophenotype but the prognosis has to be guarded in view of the rarity of this subtype. PMID:15965442

  9. Hypopigmented mycosis fungoides in Egyptian patients.

    PubMed

    Hassab-El-Naby, Hussein M M; El-Khalawany, Mohamed A

    2013-04-01

    Hypopigmented mycosis fungoides (HMF) is uncommon clinical variant that was commonly observed in dark-skinned individuals. We described the clinical characteristics, pathological features, immunohistochemical profile and prognosis of HMF in Egyptian patients. During the period from January 2004 to December 2011, we were able to diagnose and follow up 27 patients with HMF. The study included 18 males (66.7%) and 9 females (33.3%) with a mean age of 35.39 ±13.13 years. The duration ranged from 1 to 6 years with a mean of 3.26 ±1.7 years. The majority of patients were skin type IV (63%) and presented with multiple (88.9%), asymptomatic (74.1%), ill-defined (70.4%) and non-scaly (77.8%) lesions distributed on the trunk (81.5%). Histologically, epidermotropic lymphocytes were observed in 100%, basal alignment of lymphocytes in 81.5%, Pautrier's microabscesses in 29% and folliculotropism in 18.5%. Immunostaining showed predominance of epidermal CD8+ cells in 51.9% while in 29.6% CD4+ cells were predominant. Phototherapy was effective in 86.7% of patients with success rate 66.7% of narrow band (NB) ultraviolet-B and 80% of psoralen ultraviolet-A. HMF among Egyptians could be classified as non-aggressive epidermotropic cytotoxic CD8+ variant. It is common among middle age males with skin type IV and mostly well respond to phototherapy. PMID:23379648

  10. Environmental risk factors for mycosis fungoides.

    PubMed

    Wohl, Yonit; Tur, Ethel

    2007-01-01

    The rising incidence rates of mycosis fungoides (MF) call for an explanation. Thus, environmental and lifestyle factors were speculated to play a role in the development of lymphoproliferative diseases. It is thought that continuous activation of skin T helper lymphocytes leads to malignant transformation of a specific clone. Possible risk factors that have been implicated are occupational chemical exposure, radiation, drugs and infections. The carcinogenic process is probably multifactorial and multistep, combining the genetic predisposition of the individual and his immune status with various exogenous factors. Using advanced and accurate exposure assessment tools, recent epidemiological data indicate that occupational exposure to chemicals, primarily to aromatic halogenated hydrocarbons, is a major risk factor to develop MF in men (odds ratio 4.6), while exposure to pesticides, a subgroup of the aromatic halogenated hydrocarbons, is a risk factor in both genders (odds ratio 6.8 for men and 2.4 for women). Apparently, concomitant infection with Staphylococcus aureus or with Borrelia species and chronic exposure to UVR are minor risk factors for the development of MF. Further assessment of occupational and environmental exposures is essential for the evaluation of their contribution to the etiology of MF. This will allow the application of preventive and surveillance measures along with adjustment of existing health policies. PMID:17641490

  11. Mycosis fungoides progression and chronic solvent exposure.

    PubMed

    Nikkels, Arjen F; Quatresooz, Pascale; Delvenne, Philippe; Balsat, Alain; Piérard, Gérald E

    2004-01-01

    The effect of repeated exposure to specific chemicals on the initiation or progression of mycosis fungoides (MF) remains unsettled. A patient with low-grade patch stage MF progressively developed MF plaques restricted to his arms, and a tumour on his right thigh. These areas were subject to repeated exposure to solvents. His thigh was indeed in close contact with his trousers pocket where he used to store a wiping rag drenched into white spirit and cellulosic thinner. Immunophenotyping these lesions revealed a dense LCA+, CD2+, CD3+, CD4+, CD5+, CD7+, CD45+, CD45RO+ T-cell infiltrate admixed with many factor XIIIa+ dendrocytes. T-cell receptor rearrangement analysis identified a monoclonal T-cell infiltrate. An internal work-up remained negative. Stopping further solvent exposure failed to improve his condition. Oral corticotherapy combined with low-dose interferon-alpha2a halted disease progression. This observation suggests that long-term solvent exposure may trigger MF and hasten its progression from the patch stage to the plaque and tumour stages. PMID:15057012

  12. A rare presentation of erythrodermic mycosis fungoides.

    PubMed

    Goyal, Tarang; Varshney, Anupam

    2012-05-01

    Although rare, of all the cutaneous lymphoid malignancies, cutaneous T-cell lymphomas (CTCLs) constitute 65% of all lymphomas, of which 50% are patients with mycosis fungoides (MF). The erythrodermic variant of MF, a malignancy of mature, skin homing, clonal T lymphocytes, usually presents in mid to late adulthood. We present a man in his late 30s with intractable progressive erythroderma of 18 months' duration, patchy alopecia, palmoplantar keratoderma, mucosal thickening, hyperpigmentation, and intense itching as a case of erythrodermic MF. There was no systemic involvement. Diagnosis was confirmed by biopsies from multiple sites and immunohistochemistry. He was categorized with stage IIIA MF according to the International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) revised classification system. Psoralen plus UVA therapy and low-dose methotrexate resulted in clearance of lesions; regular follow-up visits were conducted to monitor progression to Sézary syndrome (SS). Progression to SS has to be monitored regularly in these patients. PMID:22768436

  13. Inflammatory vitiligo-like macules that simulate hypopigmented mycosis fungoides.

    PubMed

    Petit, Thomas; Cribier, Bernard; Bagot, Martine; Wechsler, Janine

    2003-01-01

    Two cases of an inflammatory vitiligo-like condition that simulated mycosis fungoides are reported. Both patients presented acquired hypopigmented macules sharply limited by an erythematous and papular border. The clinical aspect was suggestive of inflammatory vitiligo. Mycosis fungoides was suspected on skin specimens showing a dense band-like lymphocytic infiltrate with discrete nuclear atypias and marked exocytosis. This infiltrate was made of CD3 positive lymphocytes. CD8 positive lymphocytes were numerous in one case, few in the other. There was a loss of melanocytes in the lesional skin and absence of dominant T-cell clones in both cases. No repigmentation was observed after PUVA or local chemotherapy. The authors emphasized that erythematous and papular borders surrounding hypopigmented macules, CD8 positive lymphocytic infiltrate, absence of T-cell clonal rearrangement are helpful to rule out mycosis fungoides. PMID:12948929

  14. Hypopigmented mycosis fungoides: a review of its clinical features and pathophysiology*

    PubMed Central

    Furlan, Fabricio Cecanho; Sanches, José Antonio

    2013-01-01

    Several distinct clinical forms of mycosis fungoides have been described. Hypopigmented mycosis fungoides should be regarded as a subtype of mycosis fungoides, insofar as it presents some peculiar characteristics that contrast with the clinical features of the classical form. Most patients with hypopigmented mycosis fungoides are younger than patients typically diagnosed with classical mycosis fungoides. In addition to typical dark-skinned individuals impairment, hypopigmented mycosis fungoides has also been described in Asian patients. The prognosis for hypopigmented mycosis fungoides is much better than for classical mycosis fungoides: hypopigmented mycosis fungoides is diagnosed when there are only patches of affected skin, and lesions usually will not progress beyond terminal stages, although they can persist for many years. Diagnosis should involve clinicopathologic correlation: skin biopsy analysis often reveals intense epidermotropism, characterized by haloed, large, and atypical CD8+ lymphocytes with convoluted nuclei, in contrast to mild to moderate dermal lymphocytic infiltrate. These CD8+ cells, which participate in T helper 1-mediated immune responses, prevent evolution to mycosis fungoides plaques and tumors and could be considered the main cause of the inhibition of melanogenesis. Therefore, hypopigmentation could be considered a marker of good prognosis for mycosis fungoides. PMID:24474105

  15. Hypopigmented mycosis fungoides: a review of its clinical features and pathophysiology.

    PubMed

    Furlan, Fabricio Cecanho; Sanches, José Antonio

    2013-01-01

    Several distinct clinical forms of mycosis fungoides have been described. Hypopigmented mycosis fungoides should be regarded as a subtype of mycosis fungoides, insofar as it presents some peculiar characteristics that contrast with the clinical features of the classical form. Most patients with hypopigmented mycosis fungoides are younger than patients typically diagnosed with classical mycosis fungoides. In addition to typical dark-skinned individuals impairment, hypopigmented mycosis fungoides has also been described in Asian patients. The prognosis for hypopigmented mycosis fungoides is much better than for classical mycosis fungoides: hypopigmented mycosis fungoides is diagnosed when there are only patches of affected skin, and lesions usually will not progress beyond terminal stages, although they can persist for many years. Diagnosis should involve clinicopathologic correlation: skin biopsy analysis often reveals intense epidermotropism, characterized by haloed, large, and atypical CD8+ lymphocytes with convoluted nuclei, in contrast to mild to moderate dermal lymphocytic infiltrate. These CD8+ cells, which participate in T helper 1-mediated immune responses, prevent evolution to mycosis fungoides plaques and tumors and could be considered the main cause of the inhibition of melanogenesis. Therefore, hypopigmentation could be considered a marker of good prognosis for mycosis fungoides. PMID:24474105

  16. Juvenile mycosis fungoides diagnosed before 18 years of age.

    PubMed

    Ben-Amitai, Dan; Michael, David; Feinmesser, Meora; Hodak, Emmilia

    2003-01-01

    The literature regarding mycosis fungoides in children is sparse. To shed further light on the characteristics of mycosis fungoides in the paediatric population we analysed the clinicopathological features of 10 patients in whom this malignancy was diagnosed before the age of 18 years. All were Jews and Arabs with histologically proven patch/early plaque stage disease: 4 in stage IA, 4 in IB and 2 with unilesional disease. Seven patients had hypopigmented lesions either constituting the sole manifestation (2 patients) or in combination with classic lesions (5 patients); of these, 3 had light skin and 4 pigmented skin. Most patients had immunohistochemical features characteristic of mycosis fungoides, with a predominance of CD4+ T cells. Some had deletion of CD7+ cells. In 3 patients, however, the epidermotropic cells were exclusively or predominantly CD8+ cells. All patients responded to conventional therapy and during an average follow-up of 3.4 years only one patient showed stage progression, but without extracutaneous involvement. It is concluded that juvenile mycosis fungoides is characterized by early stage disease, occasionally with unilesional disease, usually with hypopigmented lesions irrespective of skin colour, and a good response to therapy. On the basis of our experience and review of the literature, it appears that the CD8+ phenotype is over-represented in juvenile disease. PMID:14690342

  17. Decreased CD117 expression in hypopigmented mycosis fungoides correlates with hypomelanosis: lessons learned from vitiligo.

    PubMed

    Singh, Zeba N; Tretiakova, Maria S; Shea, Christopher R; Petronic-Rosic, Vesna M

    2006-09-01

    Hypopigmented mycosis fungoides is an uncommon clinical variant of cutaneous T-cell lymphoma. We hypothesized that hypomelanosis in hypopigmented mycosis fungoides may have a similar mechanism as in vitiligo, a condition in which it is believed that alterations in expression of CD117 (stem cell factor receptor/KIT protein) on epidermal melanocytes and abnormal interactions between melanocytes and surrounding keratinocytes may play a pathogenic role. To test the hypothesis that similar mechanisms might also explain hypopigmentation in hypopigmented mycosis fungoides, skin specimens from five cases each of hypopigmented mycosis fungoides and vitiligo were studied immunohistochemically for immunophenotype of the infiltrating cells, CD117 (expressed by epidermal melanocytes), and pan melanoma cocktail of antigens (gp100, tyrosinase, and MART-1) expression; cases of conventional mycosis fungoides and normal skin were studied in parallel as controls. Our findings confirm a predominance of CD8+ neoplastic T cells in hypopigmented mycosis fungoides. Similarly, the epidermal lymphocytic infiltrate in vitiligo was also composed of CD8+ cytotoxic T cells, in contrast to an epidermal infiltrate composed of CD4+ T cells in conventional mycosis fungoides. The average number of epidermal CD117 expressing cells followed the same pattern of decreased expression in hypopigmented mycosis fungoides as in vitiligo, whereas the levels in conventional mycosis fungoides were higher, and similar to that observed in normal skin. Furthermore, a decreased number of melanocytes per high-power field of the length of the biopsy was present in hypopigmented mycosis fungoides and vitiligo, as compared with either conventional mycosis fungoides or normal skin, suggesting a correlation between decreased expression of CD117 and decreased number of melanocytes. We propose that decreased expression of CD117 and its downstream events in melanocytes may be initiated by cytotoxic effects of melanosomal

  18. 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

  19. Folliculotropic Mycosis Fungoides in an Adolescent: A Rare Case

    PubMed Central

    Mantri, Meeta Dipak; Khadke, Mona P; Ameet, Dandale L; Rachita, Dhurat S

    2016-01-01

    Folliculotropic mycosis fungoides (FMF) is an uncommon and aggressive form of mycoses fungoides with preferential involvement of head and neck region. Lesions of FMF present as erythematous plaques or papules with follicular prominences, acneiform lesions, cysts, nodules, patches of scarring alopecia, and prurigo-like lesions. The mean age of diagnosis is at 60 years and it is extremely rare in childhood and adolescence. We report a case of a 16-year-old male patient who presented with a 2-month history of an asymptomatic erythematous infiltrated plaque over the forehead. Histological examination was consistent with diagnosis of FMF. He was successfully treated with local electron beam therapy. PMID:27512205

  20. Hypopigmented mycosis fungoides in a 10-year-old boy.

    PubMed

    Manzur, A; Zaidi, S T H

    2006-01-01

    Cutaneous T-cell lymphoma (CTCL) presenting with hypopigmented lesions is an uncommon clinical variant of the disease, usually described in dark-skinned patients. We report a case of hypopigmented CTCL in a 10-year-old boy. The disease has responded favorably to narrowband UVB therapy. This case illustrates the importance of clinical suspicion for mycosis fungoides in patients with widespread hypopigmentation. PMID:17083901

  1. Hypopigmented mycosis fungoides: a clinical mimicker of vitiligo.

    PubMed

    Tolkachjov, Stanislav N; Comfere, Nneka I

    2015-02-01

    Hypopigmented mycosis fungoides (HMF) is a rare variant of cutaneous T-cell lymphoma (CTCL) that often manifests in younger patients with darker skin types in a centripetal distribution.(1) Average age of diagnosis is often 14 years.(2) The diagnosis is often missed due to its low incidence and lack of clinical suspicion. Misdiagnosis and failure to obtain biopsies lead to a long latency period from onset of hypopigmented patches to diagnosis and treatment. HMF has a clinically benign course and responds well to therapy; however, relapse is common.(3) We report a case of HMF misdiagnosed as vitiligo in order to illuminate diagnostic, histopathological, and treatment modalities. PMID:25689815

  2. 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. PMID:25814741

  3. Co-Existence of Various Clinical and Histopathological Features of Mycosis Fungoides in a Young Female

    PubMed Central

    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. PMID:25814741

  4. Granulomatous Mycosis Fungoides in an Adolescent-A Rare Encounter and Review of the Literature.

    PubMed

    Wieser, Iris; Wohlmuth, Christoph; Duvic, Madeleine

    2016-09-01

    Granulomatous mycosis fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by an infiltrate of atypical lymphocytes, histiocytes, and multinucleated giant cells. Clinically, GMF has a slowly progressing course with a worse prognosis than other forms of MF. With its peak incidence being in the fifth to sixth decade, GMF is rare in children and adolescents. Herein we describe a 14-year-old boy with GMF. PMID:27595880

  5. Early-stage mycosis fungoides variants: case-based review.

    PubMed

    Cho-Vega, Jeong Hee; Tschen, Jaime A; Duvic, Madeleine; Vega, Francisco

    2010-10-01

    Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. The diagnosis of classic MF is based on a combination of clinical presentation, histopathology, and T-cell monoclonality detected by molecular studies. However, the diagnosis can be difficult in cases of early MF because of the subtle nature of histologic findings and, in cases of variants of MF, because of the unusual clinical and/or pathologic features. In this review, we presented the most frequent variants of MF at early stage including hypopigmented, folliculotropic, pagetoid reticulosis, unilesional, granulomatous, and ichthyosis forms. This case-based clinicopathologic review provides the notion that a comprehensive clinicopathologic correlation is of substantial importance to render the diagnosis of MF. In addition, we discuss the role of molecular studies, which are highly sensitive and recently more applicable to routinely processed skin biopsy specimens in the diagnosis of MF. PMID:20850703

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

    PubMed

    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

  7. Annular hypopigmented mycosis fungoides: a novel ringed variant.

    PubMed

    Uhlenhake, Elizabeth E; Mehregan, Darius M

    2012-05-01

    Hypopigmented mycosis fungoides (MF) is a relatively uncommon variant of cutaneous lymphoma that is mostly seen in darker skin types. We present a novel and unique clinical presentation in an African-American female patient, consisting of regular hypopigmented annular rings in areas of normal skin and in more typical hypopigmented patches of MF. The lesions appeared diffusely on all extremities, anterior chest and back. Histopathologic examination showed an atypical lymphocytic infiltrate at the dermal-epidermal junction with epidermotropism and few Pautrier's collections. The patient was otherwise healthy and improved with narrowband ultraviolet (UV)-B. This case represents a presentation of a most unusual variant of hypopigmented MF, for which we propose the name 'annular hypopigmented MF'. PMID:22515225

  8. Delay in the histopathologic diagnosis of mycosis fungoides.

    PubMed

    Skov, Anne G; Gniadecki, Robert

    2015-04-01

    The diagnosis of mycosis fungoides (MF) is difficult in early stages and is based on a combination of clinical findings and histopathologic criteria. The aim of this study was to assess the diagnostic delay in MF and to investigate the rationale for multiple biopsies in a single-centre, retrospective study of 157 patients with MF. The first biopsy was diagnostic for MF in 25% of cases. The median diagnostic delay was 2.3 years and depended on whether the diagnosis was established after one or multiple biopsies. The chance of a biopsy resulting in a diagnosis of MF was 25% irrespective of the number of the biopsy in the sequence. There was a significant diagnostic delay, especially in patients in whom the initial biopsy was not specific. Sampling error and unnecessary postponement of subsequent biopsies are likely factors and therefore multiple biopsies should be considered in patients with skin lesions suggesting MF. PMID:25228392

  9. The Three Dimensional Conformal Radiotherapy for Hyperkeratotic Plantar Mycosis Fungoides

    PubMed Central

    Lee, Sun Young; Kwon, Hyoung Cheol; Cho, Yong-Sun; Nam, Kyung-Hwa; Ihm, Chull-Wan

    2011-01-01

    The localized early-stage of Mycosis fungoides (MF) (stage IA-IIA) is usually treated with topical agents, such as nitrogen mustard, steroids, and phototherapy (UVB/PUVA) as first line therapy; response to these initial treatments is usually good. However, hyperkeratotic plantar lesions are clinically rare and have decreased responsiveness to topical agents. For such cases, physicians may consider local radiotherapy. Here, a case of an 18-year-old Korean woman who was treated with three-dimensional conformal radiotherapy (3D-CRT) for hyperkeratotic plantar lesions that were refractory to UVA-1, methotrexate, and topical steroids is reported. Complete remission was attained after radiotherapy. During the one-year follow-up period, there has been no evidence of disease recurrence and no chronic complications have been observed. PMID:22028574

  10. SGN-35 in CD30-positive Lymphoproliferative Disorders (ALCL), Mycosis Fungoides (MF), and Extensive Lymphomatoid Papulosis (LyP)

    ClinicalTrials.gov

    2016-07-14

    CD-30 Positive Anaplastic Large T-cell Cutaneous Lymphoma; Lymphoma, Primary Cutaneous Anaplastic Large Cell; Lymphomatoid Papulosis; Mycosis Fungoides; Skin Lymphoma; Cutaneous Lymphomas; Lymphoma; Hematologic Disorder

  11. 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

  12. Indications of a considerable decrease in the death rate in mycosis fungoides by PUVA treatment.

    PubMed

    Swanbeck, G; Roupe, G; Sandström, M H

    1994-11-01

    PUVA therapy has its roots in ancient India and Egypt and began to come into general use in the highly developed countries in the middle of the 1970's (1). The first reports of PUVA treatment of mycosis fungoides were published in 1976 (2); these were followed by several other studies in the two following years (3-7). Some of the early work on PUVA therapy was carried out in Sweden (8,9), and the modality was in general use in most major clinics by 1977. The dramatic effect on mycosis fungoides of PUVA therapy is well known, but whether the death rate is influenced is not known. For ethical reasons no controlled clinical studies have been performed. Sweden is a highly organized country with reliable death statistics at least for diseases as conspicuous as mycosis fungoides. The purpose of the present study was to provide data on the death rate in mycosis fungoides in Sweden from 1961 to 1990, which we think is relevant to the question whether PUVA treatment decreases the death rate in mycosis fungoides. PMID:7701883

  13. Folliculotropic mycosis fungoides with large-cell transformation presenting as dissecting cellulitis of the scalp.

    PubMed

    Gilliam, A C; Lessin, S R; Wilson, D M; Salhany, K E

    1997-03-01

    Follicular mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma (CTCL) in which malignant lymphocytes preferentially infiltrate hair follicles. This report describes a patient with follicular mycosis fungoides presenting in a manner similar to dissecting cellulitis of the scalp with nonhealing, draining nodular lesions. Follicular mucinosis associated with folliculotropic mycosis fungoides resulted in follicular disruption and deep dissecting cellulitis. Large-cell transformation of CTCL was present in the initial diagnostic scalp and axillary lymph node specimens. The patient died from progressive CTCL 9 months following initial diagnosis despite electron beam radiation, topical mechlorethamine, interferon-alpha, and systemic chemotherapy. This case indicates that large-cell transformation of folliculotropic mycosis fungoides is an aggressive form of CTCL, and that folliculotropic mycosis fungoides can give rise to lesions which resemble dissecting cellulitis of the scalp. Upregulation of intercellular adhesion molecule-1 (ICAM-1) on follicular epithelium adjacent to lymphocyte function-associated antigen-1 (LFA-1)-positive folliculotropic lymphoma cells in this report provides insight into lymphocyte homing mechanisms in folliculotropic MF. PMID:9085153

  14. Mycosis fungoides in Iranian population: an epidemiological and clinicopathological study.

    PubMed

    Fatemi Naeini, Farahnaz; Abtahi-Naeini, Bahareh; Sadeghiyan, Hamidreza; Nilforoushzadeh, Mohammad Ali; Najafian, Jamshid; Pourazizi, Mohsen

    2015-01-01

    Background. Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Extensive studies on Iranian MF patients are absent. The present study aimed to produce updated clinical information on Iranian MF patients. Methods. This was a retrospective, descriptive, single-center study, including all cases of MF seen in the Department of Dermatology, University Hospital of Isfahan, Iran, between 2003 and 2013. Data systematically recorded for each patient included clinical, biological, histological, and molecular findings. Results. Eighty-six patients with clinical and histologic diagnosis of MF were included in the study. Thirty-nine patients (45.3%) were male. Female predominance was observed in patients (male : female ratio is 1 : 1.2). Patients were between 7 and 84 years of age (median: 41). The interval from disease onset to diagnosis ranged from 0 to 55 years (median: 1 year). Eighteen cases (20.9%) had unusual variants of MF. The most common types included hypopigmented and poikilodermatous MF. Childhood cases of MF constituted 5.8% (5/86) of all patients. The early stages were seen in 82 cases (95.34%). Conclusion. The major differences in epidemiologic characteristics of MF in Iran are the lack of male predominance and the lower age of patients at the time of diagnosis. PMID:25694829

  15. Profile and outcome of childhood mycosis fungoides in Singapore.

    PubMed

    Tan, E; Tay, Y K; Giam, Y C

    2000-01-01

    Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma. It usually occurs in middle-aged and elderly persons, although several reports have described its occurrence in young children. The aim of this study was to review the profile and outcome of childhood MF in Singapore from 1989 to 1998. A total of nine patients (six males and three females) were diagnosed with MF before the age of 21 years. There were four Chinese, four Malay, and one Indian. The age at the time of histologic diagnosis ranged from 6 to 20 years (mean 14.3 years). Eight of the nine patients presented with hypopigmented patches and plaques. According to TNM staging, three were in stage 1A and six in stage 1B. The treatment modalities included psoralen plus ultraviolet A (PUVA) (n = 5), UVB (n = 2), and potent topical steroids (n = 2). We found that PUVA induced a faster clinical remission, but maintenance PUVA was required to prolong the relapse-free interval. This study also highlighted the need to consider MF in the differential diagnosis of hypopigmented dermatoses in dark-skinned individuals, especially if they occur on the buttocks. PMID:11085660

  16. Mycosis Fungoides in Iranian Population: An Epidemiological and Clinicopathological Study

    PubMed Central

    Fatemi Naeini, Farahnaz; Abtahi-Naeini, Bahareh; Sadeghiyan, Hamidreza; Nilforoushzadeh, Mohammad Ali; Najafian, Jamshid; Pourazizi, Mohsen

    2015-01-01

    Background. Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Extensive studies on Iranian MF patients are absent. The present study aimed to produce updated clinical information on Iranian MF patients. Methods. This was a retrospective, descriptive, single-center study, including all cases of MF seen in the Department of Dermatology, University Hospital of Isfahan, Iran, between 2003 and 2013. Data systematically recorded for each patient included clinical, biological, histological, and molecular findings. Results. Eighty-six patients with clinical and histologic diagnosis of MF were included in the study. Thirty-nine patients (45.3%) were male. Female predominance was observed in patients (male : female ratio is 1 : 1.2). Patients were between 7 and 84 years of age (median: 41). The interval from disease onset to diagnosis ranged from 0 to 55 years (median: 1 year). Eighteen cases (20.9%) had unusual variants of MF. The most common types included hypopigmented and poikilodermatous MF. Childhood cases of MF constituted 5.8% (5/86) of all patients. The early stages were seen in 82 cases (95.34%). Conclusion. The major differences in epidemiologic characteristics of MF in Iran are the lack of male predominance and the lower age of patients at the time of diagnosis. PMID:25694829

  17. Allogeneic hematopoietic cell transplantation for mycosis fungoides and Sezary syndrome.

    PubMed

    Lechowicz, M J; Lazarus, H M; Carreras, J; Laport, G G; Cutler, C S; Wiernik, P H; Hale, G A; Maharaj, D; Gale, R P; Rowlings, P A; Freytes, C O; Miller, A M; Vose, J M; Maziarz, R T; Montoto, S; Maloney, D G; Hari, P N

    2014-11-01

    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 from 2000-2009. Median time from diagnosis to transplant was 30 (4-206) months and most subjects were with multiply relapsed/ refractory disease. The majority (64%) received non-myeloablative conditioning (NST) or reduced intensity conditioning (RIC). NST/RIC recipients were older in age compared with myeloablative recipients (median age 51 vs 44 years, P=0.005) and transplanted in recent years. Non-relapse mortality (NRM) at 1 and 5 years was 19% (95% confidence interval (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. PFS at 1 and 5 years was 31% (95% CI 22-40%) and 17% (95% CI 9-26%), respectively. OS 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 remain disease-free. PMID:25068422

  18. 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

  19. Hypomagnesemia and hypocalcemia in mycosis fungoides: a retrospective case series.

    PubMed

    Morgan, Matt; Maloney, Denise; Duvic, Madeleine

    2002-06-01

    The most common variant of cutaneous T-cell lymphomas (CTCLs) is mycosis fungoides (MF), a malignant proliferation of atypical CD4+ CD45Ro+ T-cells that initially proliferate in the skin and later invades lymph nodes and other organs including the blood (Sezary syndrome). The pathogenesis of CTCL is largely unknown. We present definitive data showing a correlation between degree and prevalence of hypomagnesemia and hypocalcemia and clinical stage of MF. Hypomagnesemia was present in 22.2% of MF patients with early stage (n = 27), 38.5% of intermediate stage (n = 13), and 67.5% of advanced stage disease (n = 40). Hypocalcemia was present in 8.3% of MF patients with early stage (n = 24), 54.5% with intermediate stage (n = 11), and 61.0% with advanced stage disease (n = 41). The odds ratios for having hypomagnesemia and hypocalcemia in patients with stage II or higher MF compared with stage I patients were 5.33 and 16.24, respectively. Hypomagnesemia has been associated with immune function abnormalities including the development of T-cell leukemia-lymphoma in rats. We hypothesize that the hypomagnesemia may play a role in the progression or pathogenesis of MF or the Sezary syndrome (SS). This retrospective case series is the first study ever to report a relationship between serum cations and CTCL in humans. PMID:12152999

  20. How I treat mycosis fungoides and Sézary syndrome.

    PubMed

    Whittaker, Sean; Hoppe, Richard; Prince, H Miles

    2016-06-23

    Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma variant and is closely related to a rare leukemic variant, Sézary syndrome (SS). MF patients at risk of disease progression can now be identified and an international consortium has been established to address the prognostic relevance of specific biologic factors and define a prognostic index. There are a lack of randomized clinical trial data in MF/SS and evidence is based on a traditional "stage-based" approach; treatment of early-stage disease (IA-IIA) involves skin directed therapies which include topical corticosteroids, phototherapy (psoralen with UVA or UVB), topical chemotherapy, topical bexarotene, and radiotherapy including total skin electron beam therapy. Systemic approaches are used for refractory early-stage and advanced-stage disease (IIB-IV) and include bexarotene, interferon α, extracorporeal photopheresis, histone deacetylase inhibitors, and antibody therapies such as alemtuzumab, systemic chemotherapy, and allogeneic transplantation. However, despite the number of biologic agents available, the treatment of advanced-stage disease still represents an unmet medical need with short duration of responses. Encouragingly, randomized phase 3 trials are assessing novel agents, including brentuximab vedotin and the anti-CCR4 antibody, mogamulizumab. A broader understanding of the biology of MF/SS will hopefully identify more effective targeted therapies. PMID:27151889

  1. TOX Acts an Oncological Role in Mycosis Fungoides

    PubMed Central

    Yu, Xin; Luo, Yixin; Liu, Jie; Liu, Yuehua; Sun, Qiuning

    2015-01-01

    Mycosis fungoides (MF) is a low-grade lymphoma characterized by clonal expansion of atypical CD4+ skin-homing T lymphocytes. Herein, we examined the role of thymocytes selection associated HMG-box (TOX), a gene previously found to be unregulated in MF skin biopsies, in MF pathogenesis. TOX encodes a high-mobility group family (HMG) domain DNA binding nuclear protein, which regulates the differentiation of developing T-cells. First, we confirmed that TOX expression levels in MF were increased compared with those in benign inflammatory dermatitis (BID) and normal skin. In addition, TOX level increased with the progression MF from patch stage to tumor stage. Overexpression of TOX accelerated the proliferation and migration of MF cell lines in vitro, which were blocked by AKT inhibitors. In conclusion, our study confirmed that TOX was highly expressed in MF lesions and accelerates the proliferation and migration of MF. TOX is a diagnostic marker for MF and may play a pathogenic role in disease progression. PMID:25811617

  2. 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

  3. 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.

  4. Pediatric mycosis fungoides in Singapore: a series of 46 children.

    PubMed

    Heng, Yee Kiat; Koh, Mark Jean Aan; Giam, Yoke Chin; Tang, Mark Boon Yang; Chong, Wei Sheng; Tan, Suat Hoon

    2014-01-01

    Few studies have evaluated Asian children with mycosis fungoides (MF). We report a series of patients from a tertiary dermatologic institution in Singapore. A retrospective review was performed of patients younger than 16 years old diagnosed with MF between 2000 and 2008 at the National Skin Centre, Singapore. Forty-six patients were identified. At initial presentation, a provisional diagnosis of MF was made in 19 patients (41.3%), pityriasis lichenoides chronica (PLC) in 11 (23.9%) and postinflammatory hypopigmentation due to eczema or other causes in 11 (23.9%). After skin biopsy, the hypopigmented variant of MF was diagnosed in 42 patients (91.3%). There was one case each of PLC-like MF, pigmented purpuric dermatosis-like MF, classic MF, and solitary MF. Pityriasis lichenoides coexisted in three cases (6.5%). All except one patient presented with the early patch-plaque stage of disease (stage IA/B). The disease did not progress in any of our patients after a mean follow-up of 71.0 ± 52.5 months. Twenty-seven patients (58.7%) had complete disease clearance after a mean duration of 27.1 ± 28.1 months; 15 (49.7%) of 32 patients who received narrowband ultraviolet B treatment had complete clearance within an average of 8.9 ± 5.3 months, but 7 patients relapsed within 14.9 ± 14.8 months. One patient with solitary MF failed multiple treatment modalities before eventually achieving disease clearance with photodynamic therapy. Hypopigmented MF is the most common MF variant in Asian children. The diagnostic difficulty is in differentiating this from PLC, which may coexist with MF. Long-term prognosis is generally favorable. PMID:24890628

  5. Follicular mycosis fungoides – A report of four Indian cases

    PubMed Central

    Rajalakshmi, T.; Inchara, Y. K.; Antony, Meryl

    2009-01-01

    Background: Follicular Mycosis Fungoides (FMF) is an under-recognized disease in India. Its clinical mimics include Hansen’s disease and Sarcoidosis. Aims: To describe the clinical and pathological features of FMF. Materials and Methods: All cases of FMF between January and December 2007 were retrieved. Cases of conventional epidermotropic MF with a minor follicular component were excluded. Slides were reviewed by two observers. The following criteria were assessed: degree and density of folliculotropism of lymphocytes, location of folliculotropism (infundibular / isthmic / bulbar), follicular mucin, eosinophils, granulomas, and conventional epidermotropism. Each feature was assigned a semi-quantitative grade. Results: There were four cases of FMF, with an equal gender distribution and a mean age of 17.5 years. All lesions were on the face. They presented as: hypopigmented patches (2) and erythematous plaques (2). Alopecia was seen in two cases. The clinical diagnosis was Hansen’s disease in all four, with a differential of Alopecia mucinosa / Sarcoidosis in two cases.The histological features seen were: disproportionate folliculotropism, lymphocyte tagging with haloes, follicular mucin, and nucleomegaly / convolution in all four cases, prominent eosinophils (2), epithelioid granulomas (1), eccrine infiltration (4), parakeratosis at the follicular ostia (2), and sebaceotropism (1). The infiltrate was bulbar (4) and isthmic (2). The rest of the epidermis showed no hint of conventional MF. Conclusion: The preferential features for FMF were involvement of face, dominant folliculotropism, nuclear atypia and convolution, and follicular mucin. Presence of granulomas and eosinophils necessitated exclusion of infectious causes. The absence of findings of MF in the rest of the epidermis should not deter pathologists from rendering this diagnosis. PMID:20838548

  6. Selected inflammatory imitators of mycosis fungoides: histologic features and utility of ancillary studies.

    PubMed

    Arps, David P; Chen, Stephanie; Fullen, Douglas R; Hristov, Alexandra C

    2014-10-01

    Mycosis fungoides is the most common primary cutaneous lymphoma; however, it remains a significant diagnostic challenge, in part because of the overlap with several inflammatory dermatoses. Despite advances in immunohistochemistry and molecular diagnostics, false-positive, false-negative, and indeterminate diagnoses are not uncommon. In most cases, the overall balance of morphologic, immunophenotypic, and genetic features must be considered carefully because there are few sensitive and specific clues to the diagnosis. Moreover, an appropriate clinical presentation is essential to the diagnosis and helps to favor or exclude inflammatory/reactive processes. Herein, we discuss 3 important inflammatory dermatoses that may closely simulate mycosis fungoides, and we review the use of ancillary studies in these challenging cases. PMID:25268195

  7. 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.

  8. [Treatment of mycosis fungoides with Zovirax (acyclovir). Study of 2 patients].

    PubMed

    Mahrle, G; Thiele, B; Steigleder, G K

    1985-04-01

    We report on two female patients suffering from mycosis fungoides, tumorous type but without systemic involvement, who have been treated with 400 mg Zovirax (Acyclovir) 3 times daily (about 15 mg/kg/day) for 12 days. The follow-up period amounted to 11 and 14 days, respectively. This therapy did not result in regression of the disease; one patient even showed progression of her skin tumors. PMID:4002770

  9. Calcitriol-induced hypercalcemia in a patient with granulomatous mycosis fungoides and end-stage renal disease.

    PubMed

    Iwakura, Takamasa; Ohashi, Naro; Tsuji, Naoko; Naito, Yoshitaka; Isobe, Shinsuke; Ono, Masafumi; Fujikura, Tomoyuki; Tsuji, Takayuki; Sakao, Yukitoshi; Yasuda, Hideo; Kato, Akihiko; Fujiyama, Toshiharu; Tokura, Yoshiki; Fujigaki, Yoshihide

    2013-05-01

    An 86-year-old man, diagnosed as having mycosis fungoides in May 2008 and treated with repeated radiation therapy, was admitted to our hospital for initiation of hemodialysis due to end-stage renal disease (ESRD) in April 2012. On admission, his corrected serum calcium level was 9.3 mg/dL, and his intact parathyroid hormone level was 121.9 pg/mL (normal range 13.9-78.5 pg/mL), indicating secondary hyperparathyroidism due to ESRD. After starting hemodialysis, urinary volume diminished rapidly. The serum calcium level increased (12.7 mg/dL), and the intact parathyroid hormone level was suppressed (< 5 pg/mL), while the 1,25-dihydroxyvitamin D3 (calcitriol) level increased (114 pg/mL, normal range: 20.0-60.0 pg/mL) in June 2012. The possibilities of sarcoidosis and tuberculosis were ruled out. Skin biopsies from tumorous lesions revealed a diagnosis of granulomatous mycosis fungoides. The serum soluble interleukin-2 receptor levels and the degrees of skin lesions went in parallel with the increased serum calcium and calcitriol levels. Therefore, the patient was diagnosed as having calcitriol-induced hypercalcemia possibly associated with granulomatous mycosis fungoides. Granulomatous mycosis fungoides is rare, and its association with calcitriol-induced hypercalcemia has not been reported. Careful attention to calcium metabolism is needed in patients with granulomatous mycosis fungoides, especially in patients with ESRD. PMID:24175265

  10. Hypopigmented mycosis fungoides in type v skin: a report of 5 cases.

    PubMed

    Ranawaka, Ranthilaka R; Abeygunasekara, Priyanka H; de Silva, M V Chandu

    2011-01-01

    Five patients with type V skin were studied to describe the clinical manifestations, pathological features, and treatment response in hypopigmented mycosis fungoides (HMF). The mean age of patients was 22.4 years at diagnosis, with a mean of 36 months of diagnostic delay. Two were children aged 11 and 13 years. Skin patches were limited to sunlight-covered body areas. In tropical climate, exposure to natural sunlight possibly cured the lesions on sun-exposed areas at early stage of onset. HMF may frequently be misinterpreted as eczema, vitiligo, or progressive macular hypomelanosis clinically and histopathologically as seen in our case series. PMID:23198169

  11. Inflammatory vitiligo versus hypopigmented mycosis fungoides in a 58-year-old Indian female.

    PubMed

    Soro, Luis A; Gust, Anthony J; Purcell, Stephen M

    2013-10-01

    Vitiligo, particularly the rarer inflammatory variant, may be difficult to distinguish from hypopigmented mycosis fungoides (MF) clinically. Complicating the distinction is that when biopsies are taken from the periphery of early vitiliginous lesions or from lesions with an inflammatory border (inflammatory vitiligo), a dermal lymphocytic infiltrate, exocytosis, interface dermatitis, and mild spongiosis may be seen, all resembling the findings seen in hypopigmented MF. We present a case demonstrating the difficulty in differentiating between these two diseases and examine some characteristic clinical and histopathological features of each. Often, a conclusive diagnosis cannot be made, necessitating close follow-up of the patient and monitoring for progression of their disease over time. PMID:24350017

  12. Hypopigmented Mycosis Fungoides in Type V Skin: A Report of 5 Cases

    PubMed Central

    Ranawaka, Ranthilaka R.; Abeygunasekara, Priyanka H.; de Silva, M. V. Chandu

    2011-01-01

    Five patients with type V skin were studied to describe the clinical manifestations, pathological features, and treatment response in hypopigmented mycosis fungoides (HMF). The mean age of patients was 22.4 years at diagnosis, with a mean of 36 months of diagnostic delay. Two were children aged 11 and 13 years. Skin patches were limited to sunlight-covered body areas. In tropical climate, exposure to natural sunlight possibly cured the lesions on sun-exposed areas at early stage of onset. HMF may frequently be misinterpreted as eczema, vitiligo, or progressive macular hypomelanosis clinically and histopathologically as seen in our case series. PMID:23198169

  13. Hypopigmented mycosis fungoides: a report of 7 cases and review of the literature.

    PubMed

    Stone, M L; Styles, A R; Cockerell, C J; Pandya, A G

    2001-02-01

    Over the last 2 decades, hypopigmented macules have been reported with increasing frequency as an initial presentation of mycosis fungoides (MF). We retrospectively reviewed 7 patients with hypopigmented MF. The mean age was 35 years at disease onset, with a mean of 5.5 years' duration of illness before presentation. All of our patients were Fitzpatrick skin type IV or V, and most reported pruritus. Histologic findings in all cases were consistent with MF. Treatment with topical nitrogen mustard produced repigmentation in 4 of 6 patients. PMID:11236223

  14. Inflammatory vitiligo versus hypopigmented mycosis fungoides in a 58-year-old Indian female

    PubMed Central

    Soro, Luis A.; Gust, Anthony J.; Purcell, Stephen M.

    2013-01-01

    Vitiligo, particularly the rarer inflammatory variant, may be difficult to distinguish from hypopigmented mycosis fungoides (MF) clinically. Complicating the distinction is that when biopsies are taken from the periphery of early vitiliginous lesions or from lesions with an inflammatory border (inflammatory vitiligo), a dermal lymphocytic infiltrate, exocytosis, interface dermatitis, and mild spongiosis may be seen, all resembling the findings seen in hypopigmented MF. We present a case demonstrating the difficulty in differentiating between these two diseases and examine some characteristic clinical and histopathological features of each. Often, a conclusive diagnosis cannot be made, necessitating close follow-up of the patient and monitoring for progression of their disease over time. PMID:24350017

  15. Managing Patients with Cutaneous B-Cell and T-Cell Lymphomas Other Than Mycosis Fungoides.

    PubMed

    Kheterpal, Meenal; Mehta-Shah, Neha; Virmani, Pooja; Myskowski, Patricia L; Moskowitz, Alison; Horwitz, Steven M

    2016-06-01

    Cutaneous lymphomas (CL) are a heterogeneous group of neoplasms characterized with clinical and histopathological variation, as well as overlap with benign dermatoses. Diagnosis and treatment of CLs is challenging and often requires a multidisciplinary approach. However, prognostic knowledge of these conditions and awareness of treatment options can help optimize appropriate use of available regimens, thereby improving care for patients. Here, we review the most recent literature and outline treatment themes for managing patients with cutaneous B-cell and T-cell lymphomas other than mycosis fungoides. PMID:27101016

  16. 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. PMID:26433848

  17. Follow-up of patients with mycosis fungoides after interferon α2b treatment failure

    PubMed Central

    Studziński, Maciej; Giebel, Sebastian; Krause, Anna; Olejniczak, Monika; Grzanka, Aleksandra

    2015-01-01

    Introduction Treatment of T cell cutaneous lymphoma( CTCL) is a controversial subject and the effectiveness of treatment is still low. Aim Report of single center experience of management CTCL after progression after first line treatment. Material and methods We present 41 patients with CTCL, 29 received interferon α2b in first line, and 12 of them received second line therapy. Results Overall response rate for second line therapy was 60%. Conclusions Results of the follow-up of patients with mycosis fungoides after interferon α2b treatment failure with the literature review and discussion. PMID:26015774

  18. Frequency of hypopigmented mycosis fungoides in Egyptian patients presenting with hypopigmented lesions of the trunk.

    PubMed

    Abdel-Halim, Mona; El-Nabarawy, Eman; El Nemr, Reham; Hassan, Abeer M

    2015-11-01

    Hypopigmented mycosis fungoides (HMF) is an uncommon variant of mycosis fungoides with an unknown exact frequency. We aimed to study the frequency of HMF in a cohort of Egyptian patients presenting to a tertiary care center in Cairo, Egypt, with hypopigmented lesions of the trunk. Hundred patients with hypopigmented lesions involving the trunk (with or without other sites involvement) were subjected to thorough clinical and histopathological examination. Immunohistochemical studies (S100, CD4, and CD8) were performed when indicated. Constellation of findings was used to reach a final diagnosis. Sixteen cases had HMF (16%). Other than HMF, our cohort included hypopigmented parapsoriasis en plaque (42 cases), postinflammatory hypopigmentation (28 cases), progressive macular hypomelanosis (12 cases), and pityriasis alba (2 cases). In comparison with other hypopigmented disorders, HMF was significantly associated with progressive disease course (P = 0.004), affection of distal upper limbs (P = 0.005), proximal lower limbs (P = 0.003), large-sized lesions (>5 cm) (P < 0.0001), well-defined margin (P < 0.0001), scaliness (P = 0.002), erythema (P < 0.0001), atrophy (P = 0.012), and mottled pigmentation (P < 0.0001). Awareness of HMF and its characteristic clinical features is mandatory to avoid underdiagnosis or overdiagnosis with subsequent morbidity or unnecessary aggressive therapy, respectively. PMID:26262921

  19. Mycosis fungoides and Sézary syndrome: Current challenges in assessment, management and prognostic markers.

    PubMed

    Hughes, Charlotte Fm; Newland, Kate; McCormack, Christopher; Lade, Stephen; Prince, H Miles

    2016-08-01

    Mycosis fungoides and Sézary syndrome are the most common variants of the cutaneous T-cell lymphomas. Assessment of a patient with a suspected diagnosis requires thorough history taking and physical examination, in combination with skin biopsy. In some cases flow cytometry, molecular studies and imaging are also required in order to diagnose and stage the disease. Staging is derived from the tumour-node-metastasis-blood classification and is currently our best attempt to stratify prognosis and hence guide management in this complex disease. Many other clinical, biological and pathological factors may help to distinguish groups at risk and predict prognosis more accurately. Management remains heavily guided by staging, such that patients with early-stage disease generally begin treatment with skin-directed or local therapies and those with advanced-stage disease have many treatment options, including chemotherapy, the use of biological agents, local and total body radiotherapy, as well as haematopoietic stem cell transplantation. Besides staging, many other patient-related factors influence the treatment strategy, particularly where symptom relief is paramount. There are many challenges remaining in the study of Mycosis fungoides and Sézary syndrome and, given the rarity of the disease, concerted worldwide efforts are required to conduct efficient and effective research. PMID:25988337

  20. 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.

  1. Coexistence of patch stage mycosis fungoides and interstitial granuloma annulare in the same patient: a pitfall in the clinicopathologic diagnosis of mycosis fungoides.

    PubMed

    Koochek, Arash; Fink-Puches, Regina; Cerroni, Lorenzo

    2012-04-01

    Several clinical and histopathologic variants of mycosis fungoides (MF) have been well described, including the often elusive interstitial MF. Differentiation from other inflammatory disorders, such as interstitial granuloma annulare (GA) and inflammatory morphea, may be extremely difficult. We report a case of MF and GA coexisting in a 54-year-old woman who initially presented to clinic in 2000 with slightly scaly patches on the trunk and extremities, histopathologically diagnostic of MF. A second biopsy taken a few months later revealed an interstitial infiltrate that was initially interpreted as interstitial MF. Over the following 10 years, additional biopsies revealed features of conventional MF. In 2009, a new biopsy showed unequivocal features of interstitial GA. Reevaluation of the original biopsy, diagnostic of "interstitial MF," revealed that this, too, could be better classified as interstitial GA than interstitial MF. Our case illustrates that MF and interstitial GA may coexist simultaneously, thus representing a pitfall in the histopathologic diagnosis of MF. Given the similarities in clinicopathologic presentation, dermatologists and dermatopathologists should be cautious not to inadvertently misinterpret GA as interstitial MF. PMID:22240773

  2. Treatment of pruritus in early-stage hypopigmented mycosis fungoides with aprepitant.

    PubMed

    Jiménez Gallo, David; Albarrán Planelles, Cristina; Linares Barrios, Mario; Fernández Anguita, María José; Márquez Enríquez, Juan; Rodríguez Mateos, María Eugenia

    2014-01-01

    Pruritus is a symptom that significantly affects the patient's quality of life in cutaneous T cell lymphoma (CTCL). The most effective treatments are those that address the condition itself; however, it is often not possible to control this symptom. Lymphoma-related pruritus normally becomes more severe as CTCL progresses, constituting an important factor for quality of life in these patients. Substance P is a neuromodulator which appears to play a key role in pruritus. Aprepitant is a neurokinin-1 receptor antagonist affecting the substance P receptor. So far, several cases have been documented with an antipruritic response to the drug aprepitant in advanced-stage mycosis fungoides (MF). In this paper, we describe an excellent response to aprepitant in a female patient with severe pruritus secondary to hypopigmented stage I MF. We would also like to stress the absence of nausea and vomiting of this combined therapy of interferon and aprepitant. Aprepitant could improve tolerance to interferon. PMID:24517320

  3. Efficacy of narrowband ultraviolet B twice weekly for hypopigmented mycosis fungoides in Asians.

    PubMed

    Kanokrungsee, S; Rajatanavin, N; Rutnin, S; Vachiramon, V

    2012-03-01

    Hypopigmented mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma. To date, there have been no data published about the efficacy of a twice-weekly regimen of narrowband ultraviolet B (NB-UVB) for the treatment of hypopigmented MF. We retrospectively reviewed 11 patients with hypopigmented MF who were treated with NB-UVB twice weekly between 2001 and 2010. Of the 11 patients, 7 achieved a complete response with a mean of 40 treatments; the remaining 4 patients had a partial response. Upon discontinuation of treatment, three patients had clinical relapse after complete remission. Median time to relapse was 10 months. A twice-weekly regimen of NB-UVB is an effective treatment for hypopigmented MF with minimal side-effects. However, the relapse rate is high, and unfortunately, no clinical or histological features can predict the relapse of the disease. PMID:22276982

  4. [Autologous hematopoietic stem cell transplantation followed by oral bexarotene in a patient with advanced mycosis fungoides].

    PubMed

    Pérez-Barrio, S; Izu, R; García-Ruiz, J C; Acebo, E; Martínez de Lagrán, Z; Díaz-Pérez, J L

    2008-09-01

    We describe the case of a 17-year-old patient with rapidly progressing and aggressive mycosis fungoides, with multiple cutaneous tumors and large cell transformation. She was initially treated with 3 cycles of high-dose chemotherapy with mega-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) without response, leading to the decision to undertake autologous hematopoietic stem cell transplantation. Partial remission of the disease was achieved with this treatment and subsequent introduction of oral bexarotene led to complete remission, which has been maintained for more than 3 years with good tolerance of oral therapy. We discuss the advantages and disadvantages of autologous hematopoietic stem cell transplantation and the use of oral bexarotene. PMID:18682170

  5. The utility of bexarotene in mycosis fungoides and Sézary syndrome

    PubMed Central

    Panchal, Manisha R; Scarisbrick, Julia J

    2015-01-01

    Cutaneous T-cell lymphoma (CTCL) is an umbrella term that encompasses a group of neoplasms that have atypical T-lymphocytes in the skin. Mycosis fungoides (MF) is the most common type of CTCL and Sézary syndrome (SS) is the leukemic form. Treatment for CTCL is dependent on the stage of disease and response to previous therapy. Therapy is divided into skin-directed treatment, which tends to be first line for early-stage disease, and systemic therapy, which is reserved for refractory CTCL. Bexarotene is a rexinoid and was licensed in Europe in 2002 for use in patients with advanced disease that have been refractory to a previous systemic treatment. We review the use of bexarotene as monotherapy and in combination with other treatments. PMID:25678803

  6. 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. PMID:26630682

  7. [Gemcitabine Monotherapy for Advanced Mycosis Fungoides--Two Case Reports and a Literature Review].

    PubMed

    Masuzawa, Mamiko; Takasu, Hiroshi; Amoh, Yasuyuki

    2015-12-01

    Gemcitabine, a pyrimidine nucleoside analogue, is gaining recognition as a potential therapeutic agent for advanced-stage and refractory cutaneous T-cell lymphoma (CTCL). We report of 2 patients whose advanced-stage mycosis fungoides was not sufficiently controlled by prior CHOP therapy. Both patients showed great improvement in the skin lesions with weekly gemcitabine therapy (1,000-1,200 mg/m2). The patients received four and 8 cycles of gemcitabine monotherapy, respectively, and no grade 3-4 hematological or hepatic adverse events occurred. This is the first report of the efficacy of gemcitabine for CTCL in Japan. Gemcitabine is well tolerated and is an effective monotherapy for CTCL. PMID:26809303

  8. Flow Cytometric Analysis of T, B, and NK Cells Antigens in Patients with Mycosis Fungoides

    PubMed Central

    Yazıcı, Serkan; Bülbül Başkan, Emel; Budak, Ferah; Oral, Barbaros; Adim, Şaduman Balaban; Ceylan Kalin, Zübeyde; Özkaya, Güven; Aydoğan, Kenan; Saricaoğlu, Hayriye; Tunali, Şükran

    2015-01-01

    We retrospectively analyzed the clinicopathological correlation and prognostic value of cell surface antigens expressed by peripheral blood mononuclear cells in patients with mycosis fungoides (MF). 121 consecutive MF patients were included in this study. All patients had peripheral blood flow cytometry as part of their first visit. TNMB and histopathological staging of the cases were retrospectively performed in accordance with International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) criteria at the time of flow cytometry sampling. To determine prognostic value of cell surface antigens, cases were divided into two groups as stable and progressive disease. 17 flow cytometric analyses of 17 parapsoriasis (PP) and 11 analyses of 11 benign erythrodermic patients were included as control groups. Fluorescent labeled monoclonal antibodies were used to detect cell surface antigens: T cells (CD3+, CD4+, CD8+, TCRαβ+, TCRγδ+, CD7+, CD4+CD7+, CD4+CD7−, and CD71+), B cells (HLA-DR+, CD19+, and HLA-DR+CD19+), NKT cells (CD3+CD16+CD56+), and NK cells (CD3−CD16+CD56+). The mean value of all cell surface antigens was not statistically significant between parapsoriasis and MF groups. Along with an increase in cases of MF stage statistically significant difference was found between the mean values of cell surface antigens. Flow cytometric analysis of peripheral blood cell surface antigens in patients with mycosis fungoides may contribute to predicting disease stage and progression. PMID:26788525

  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. PMID:23724870

  10. 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

  11. Mycosis fungoides--an underwriting prospective with emphasis on staging and risk selection.

    PubMed

    Iacovino, J R

    1994-01-01

    Mycosis Fungoides is a T-cell lymphoma having a broad clinical spectrum ranging from localized cutaneous to rapidly fatal systemic disease. Early clinical presentation is non specific, delaying correct diagnosis. Compared to clinical, the insurable spectrum is narrow. Staging for skin, lymph node and other organ manifestations is presented. Factors which influence mortality within each stage are elucidated. The survival curves of stages and stage groupings are illustrated and discussed to facilitate risk classification. Cutaneous (T) and lymph node (LN) stages are the most important prognosticators. Substages T1/T2, LN1/LN2 without associated palpable adenopathy, eosinophilia, visceral and blood positive findings are insurable. It would be most appropriate to place them in a tumor class of mild/moderate risk after the initial excessive mortality period ends. Higher T and LN substages, adenopathy and visceral disease have highly adverse mortality. These ultimately reveal a flattening of survival curves at 8-10 years. Although numerous treatment modalities have been used, none appear to consistently prolong life expectancy except in the earliest stage skin disease. PMID:10147101

  12. Hypopigmented mycosis fungoides in childhood and adolescence: a long-term retrospective study.

    PubMed

    Castano, Ekaterina; Glick, Sharon; Wolgast, Lucia; Naeem, Rizwan; Sunkara, Jaya; Elston, Dirk; Jacobson, Mark

    2013-11-01

    Patients with hypopigmented mycosis fungoides (HMF) present at a younger age than those with classic MF. Our goal was to describe the clinical presentation, histopathologic features and long-term outcome in patients who developed HMF before the age of 21. It was observed that among 69 pediatric patients diagnosed with MF between 1992 and 2010, 50 had HMF. Thirty-five patients had clinical follow-up. There were 37 males and 32 females with a mean age of 13.6 years. Most patients were African American or Hispanic and presented with multiple hypopigmented patches. All biopsies showed epidermotropism of T-lymphocytes, whereas fibroplasia and lichenoid infiltrate were variable. All specimens tested were CD8+. Treatment modalities included topical steroids, narrow band ultraviolet B and psoralen and ultraviolet A. HMF patients were followed for <1-12 years. Most children responded to treatment, but recurrence rates were high. One patient progressed to plaque/tumor stage. Others did not progress; however, many were lost to follow-up. We present a large cohort of children with HMF and report on the features of disease and progression. A major difference in histology of HMF was lack of fibroplasia and lichenoid infiltrate, probably because of presentation in the early patch stage. Most patients have a waxing-and-waning course and relapse after discontinuation of therapy, requiring repetitive treatment. PMID:24320808

  13. Mycosis fungoides in Arab children and adolescents: a report of 36 patients from Kuwait.

    PubMed

    Nanda, Arti; AlSaleh, Qasem A; Al-Ajmi, Hejab; Al-Sabah, Homoud; Elkashlan, Muhammad; Al-Shemmari, Salem; Demierre, Marie-France

    2010-01-01

    Mycosis fungoides (MF) is rare in children and adolescents. This study was aimed to determine the clinicoepidemiologic features of juvenile onset (≤18 yrs) MF in Kuwait. Thirty-six children and adolescents (≤18 yrs) with MF registered in a referral photobiology unit for cutaneous lymphomas between July 1991 and June 2009 were included in this study. Children and adolescents were observed to constitute 16.6% of the total number of patients with MF, with 97% of patients of Arab ethnicity. The age-adjusted incidence rate of MF in children and adolescents among the total population was 0.29/100,000 persons/year. Among 36 Arab children and adolescents, boys outnumbered girls by 1.25:1. Mean and median age at onset of disease was 9 years, and age at diagnosis was 13 years. Patch stage disease was the most common clinical variant (75%) with 56% with pure hypopigmented MF-variant. The majority of patients (75%) had stage IB (TNM and B staging) disease. The study highlights a high prevalence and incidence of juvenile MF in Kuwait with a predominantly hypopigmented presentation. PMID:21138468

  14. Hypopigmented mycosis fungoides: frequent expression of a CD8+ T-cell phenotype.

    PubMed

    El-Shabrawi-Caelen, Laila; Cerroni, Lorenzo; Medeiros, L Jeffrey; McCalmont, Timothy H

    2002-04-01

    Hypopigmented mycosis fungoides (MF) is a form of cutaneous T-cell lymphoma in which hypopigmentation occurs in the absence of classic lesions of MF. Hypopigmented MF predominantly affects people with dark complexions. The natural history of this variant of cutaneous T-cell lymphoma is similar to that of conventional MF, although the disease onset is usually in childhood or adolescence. In a retrospective study we evaluated the clinical, histopathologic, immunohistochemical, and molecular characteristics of hypopigmented MF in 15 patients. Similar to other reports, the disease onset occurred in childhood and adolescence in most of the cases. The survival rate was comparable with that of classic MF. We did not observe progression to systemic disease or lymph node involvement. Histopathologically hypopigmented lesions were indistinguishable from hyperpigmented or erythematous patches. On immunohistochemical analysis a predominantly CD8+ infiltrate was detected in the majority of cases (nine of 15 patients). To determine whether epidermotropic CD8+ T cells represent the malignant T-cell clone or whether these cells are innocent, tumor-infiltrating T lymphocytes, we performed microdissection of epidermotropic CD8+ T cells and analyzed T-cell receptor-gamma chain gene for rearrangements. The epidermotropic CD8+ T lymphocytes showed clonal T-cell receptor gene rearrangement and therefore represented the malignant T-cell clone. We conclude that hypopigmented MF tends to occur in young people and that it belongs to the group of CD8+ cutaneous T-cell lymphomas in the majority of cases. PMID:11914622

  15. A new protoparvovirus in human fecal samples and cutaneous T cell lymphomas (mycosis fungoides).

    PubMed

    Phan, Tung G; Dreno, Brigitte; da Costa, Antonio Charlys; Li, Linlin; Orlandi, Patricia; Deng, Xutao; Kapusinszky, Beatrix; Siqueira, Juliana; Knol, Anne-Chantal; Halary, Franck; Dantal, Jacques; Alexander, Kathleen A; Pesavento, Patricia A; Delwart, Eric

    2016-09-01

    We genetically characterized seven nearly complete genomes in the protoparvovirus genus from the feces of children with diarrhea. The viruses, provisionally named cutaviruses (CutaV), varied by 1-6% nucleotides and shared ~76% and ~82% amino acid identity with the NS1 and VP1 of human bufaviruses, their closest relatives. Using PCR, cutavirus DNA was found in 1.6% (4/245) and 1% (1/100) of diarrhea samples from Brazil and Botswana respectively. In silico analysis of pre-existing metagenomics datasets then revealed closely related parvovirus genomes in skin biopsies from patients with epidermotropic cutaneous T-cell lymphoma (CTCL or mycosis fungoides). PCR of skin biopsies yielded cutavirus DNA in 4/17 CTCL, 0/10 skin carcinoma, and 0/21 normal or noncancerous skin biopsies. In situ hybridization of CTCL skin biopsies detected viral genome within rare individual cells in regions of neoplastic infiltrations. The influence of cutavirus infection on human enteric functions and possible oncolytic role in CTCL progression remain to be determined. PMID:27393975

  16. Mycosis fungoides: Positron emission tomography/computed tomography in staging and monitoring the effect of therapy

    PubMed Central

    D’Souza, Maria Mathew; D’Souza, Paschal; Sharma, Rajnish; Jaimini, Abhinav; Mondal, Anupam

    2015-01-01

    A 58-year-old woman, diagnosed as a case of mycosis fungoides (MF), underwent [18F]-fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT) examination. The study revealed intense FDG uptake in a large ulceroproliferative right thigh lesion, indurated plaques in the chest wall and left thigh, along with multiple sites of cutaneous involvement, axillary and inguinal lymphadenopathy. The patient underwent chemotherapy with CHOP regimen, radiotherapy for the right thigh lesion, along with topical corticosteroids and emollients for the disseminated cutaneous involvement. Repeat [18F]-FDG PET/CT study performed a year later, showed near complete disease regression specifically of the ulceroproliferative lesion and indurated cutaneous plaques, no change in lymphadenopathy, and a subtle diffuse progression of the remaining cutaneous lesions. A multidisciplinary approach to the diagnosis, staging and treatment of MF has long been suggested for optimizing outcomes from management of patients with this disease. This case highlights the potential role of incorporating PET/CT as a single modality imaging technique in the staging and assessment of response to therapy. PMID:25829740

  17. Syringotropic mycosis fungoides responding well to VELP chemotherapy: A case report

    PubMed Central

    LUO, YANG; ZHANG, LI; SUN, YU-JIAO; DU, HUA; YANG, GUI-LAN

    2016-01-01

    Mycosis fungoides (MF), a low-malignant lymphoproliferative disorder, is the most common type of cutaneous T-cell lymphoma. The current study reported a case of syringotropic MF, a rare variant of MF, which presented with reactive B cell proliferation, lymphoid follicle formation, hair loss and lymphadenopathy. The clinical manifestations of the patient were MF-like lumps. Immunohistochemical staining of AE1/AE3 showed that there were abundant infiltrated lymphocytes surrounding the syringocystadenoma. In addition, the direction of the lymphocyte arrangement was consistent with the meandering direction of syringocystadenoma. The patient did not respond to 1-month narrowband (311-nm) ultraviolet therapy; however, a good response was obtained subsequent to one cycle of chemotherapy with vincristine sulfate, etoposide, L-asparaginase and prednisone acetate (know as the VELP regimen). After 7 days of VELP chemotherapy, the skin lesions were ameliorated, hair loss was improved and lymphadenopathy disappeared. No lymphadenopathy or new skin lesions were observed during 6 months of follow-up. PMID:27313668

  18. Decreased interleukin-21 expression in skin and blood in advanced mycosis fungoides.

    PubMed

    Kabasawa, Miyoko; Sugaya, Makoto; Oka, Tomonori; Takahashi, Naomi; Kawaguchi, Makiko; Suga, Hiraku; Miyagaki, Tomomitsu; Takahashi, Takehiro; Shibata, Sayaka; Fujita, Hideki; Asano, Yoshihide; Tada, Yayoi; Kadono, Takafumi; Okochi, Hitoshi; Sato, Shinichi

    2016-07-01

    Interleukin (IL)-21 is regarded as a potent antitumor agent, which increases the cytotoxicity of both natural killer (NK) and CD8(+) T cells. In this study, we investigated the role of IL-21 in mycosis fungoides (MF). IL-21 mRNA expression levels in patch and plaque MF were significantly higher than those in normal skin. IL-21 mRNA expression levels in tumor MF were significantly decreased compared with those in patch and plaque MF. Interestingly, mRNA expression levels of IL-21 in MF lesional skin significantly correlated with those of T-helper type-1 cytokines/chemokines such as CXCL10, CXCL11 and γ-interferon. Immunohistochemistry showed that IL-21 was expressed by keratinocytes in patch and plaque MF. Furthermore, serum IL-21 levels in patients with tumor MF were significantly lower than those of healthy controls and plaque MF. Thus, IL-21 expression was significantly downregulated in skin and blood of patients with tumor MF, which may contribute to progression of MF. Our study suggests that recombinant IL-21 would be a promising therapy for MF. PMID:26825047

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

    PubMed Central

    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. PMID:26989539

  20. Interferon and low dose methotrexate improve outcome in refractory mycosis fungoides/Sézary syndrome.

    PubMed

    Avilés, Agustin; Nambo, M Jesús; Neri, Natividad; Castañeda, Claudia; Cleto, Sergio; Gonzalez, Martha; Huerta-Guzmán, Judith

    2007-12-01

    Treatment of refractory mycosis fungoides and Sézary syndrome remain unsatisfactory. In this study, we assessed the efficacy and toxicity of low-dose methotrexate (10 mg/m(2), biweekly) and interferon (9.0 MU, three times a week) as induction therapy by 6 or 12 months, followed, if patients achieved a complete remission, by interferon maintenance until toxicity or relapse. In an intent-to-treat analysis, 158 patients were considered evaluable. Complete response (biopsy proven) was observed in 112 patients (49 [31%] at 6 months and 63 [49%] at 12 months); thus, the complete response rate was 74%. With a median follow-up of 155 months (range, 62-181), progression-free disease was 71% and overall survival was 69%. Acute toxicity was mild, treatment was well tolerated, and to date no late toxicity has been observed. We conclude that this regimen is a benefit to this setting of patients, with excellent outcome and mild toxicity. PMID:18158775

  1. Granuloma annulare with a mycosis fungoides-like distribution and palisaded granulomas of CD68-positive histiocytes.

    PubMed

    Wu, Hong; Barusevicius, Alan; Lessin, Stuart R

    2004-07-01

    We describe 3 unusual cases of granuloma annulare with multiple macular lesions in a distribution that simulated mycosis fungoides in patients with no associated underlying diseases. Repeated biopsies showed typical well-formed palisading granulomas and no evidence of an atypical lymphocytic infiltrate. There was no vasculitis, neutrophilic, eosinophilic, or interstitial infiltrate. The patients had no associated underlying diseases. Most of the histiocytes in the palisading granulomas were strongly positive for CD68. The lymphocytes were a minor component of the granulomatous inflammation and were predominantly CD8(+) T-cells. The findings in these cases add to the spectrum of previously defined granulomatous eruptions of the skin. PMID:15243522

  2. 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.

  3. Vitiligo vs. hypopigmented mycosis fungoides (histopathological and immunohistochemical study, univariate analysis).

    PubMed

    El-Darouti, Mohammad A; Marzouk, Salonaz A; Azzam, Omar; Fawzi, Marwa Mohsen; Abdel-Halim, Mona R E; Zayed, Amira A; Leheta, Tahra M

    2006-01-01

    Vitiligo is a common skin disease characterized by the presence of well circumscribed, depigmented milky white macules devoid of identifiable melanocytes. On the other hand, hypopigmented mycosis fungoides (MF) is a rare variant of MF which presents clinically as persistent hypopigmented macules and patches. Both disorders show a predominance of CD8+ T cells in tissue samples and hence the differentiation between the two diseases on clinical, histopathological and even immunohistochemical grounds may offer great difficulty. The aim of this work is to identity certain histopathological clues which might help to differentiate between the two diseases. The study included 54 patients (26 vitiligo patients and 28 patients with Hypopigmented MF). Skin biopsies were taken and examined by hematoxylin and eosin and CD3, CD4 and CD8 markers were performed for ten vitiligo and nine MF patients. We have found that epidermotropism, hydropic degeneration of basal cells, partial loss of pigment, preservation of some melanocytes, presence of lymphocytes within the papillary dermis, increased density of the dermal infiltrate and wiry fibrosis of the papillary dermal collagen were detected with a significantly higher incidence in hypopigmented MF rather than vitiligo (P-values < 0.0001, < 0.00011, < 0.00011, = 0.001, = 0.008 and = 0.001 respectively). On the other hand, focal thickening of the basement membrane, complete loss of pigmentation, total absence of melanocytes, as well as absence or sparsness of lymphocytes in the dermal papillae were seen much more frequently in vitiligo. Statistical analysis of these differences was significant with P-values < 0.00011, < 0.00011, < 0.00011, = 0.008 respectively, regarding these pathological criteria. We conclude that differentiation of hypopigmented MF from vitiligo is possible by relying on the histopathological clues described in this study. This is particularly useful in areas of the world where cost benefit is crucial. PMID:16436337

  4. Childhood mycosis fungoides: experience of 28 patients and response to phototherapy.

    PubMed

    Laws, Philip M; Shear, Neil H; Pope, Elena

    2014-01-01

    Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is rare in childhood. The prognosis and response to treatment are poorly described in children. The objective of the current study was to evaluate the response to phototherapy in a pediatric cohort. A retrospective cohort study of all patients diagnosed with MF before the age of 18 years and referred to the regional CTCL phototherapy service was performed between January 1990 and April 2012. Twenty-eight patients were identified (13 boys, 15 girls). The mean age at presentation was 11.6 ± 3.9 years. The hypopigmented variant was noted in 79% of patients. All patients had stage I disease (IA = 10, IB = 17, unknown = 1). The median follow-up after diagnosis was 43 months (range 6-274 mos). Narrowband ultraviolet B (NbUVB; 311 nm) was used as first-line phototherapy in 18 patients and psoralen (bath) plus ultraviolet A (PUVA) was used in 8 patients. Complete or partial response was observed in 19 of 22 patients (86%). A further course of phototherapy was required in 7 of 12 patients (58%) treated with NbUVB after a median of 4 months (range 4-29 mos). A further course of phototherapy was required in four of eight patients (50%) successfully treated with PUVA after a median of 45.5 months (range 30-87 mos). No disease progression was noted over the follow-up (median 43 mos). The majority of patients in our cohort had hypopigmented MF. Phototherapy offers an effective option for treatment of childhood MF, although the period of remission may be greater in patients treated with PUVA. PMID:24916067

  5. 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

  6. Retrospective 5-year review of 131 patients with mycosis fungoides and Sézary syndrome seen at the National Skin Centre, Singapore.

    PubMed

    Tan, Eugene Sern Ting; Tang, Mark Boon Yang; Tan, Suat Hoon

    2006-11-01

    A total of 131 new cases of mycosis fungoides and Sézary syndrome were diagnosed clinically and histopathologically at our centre over a 5-year period. There were 87 males and 44 females with a mean age of 36.3 years (range 3-87 years) and no racial predilection. Of the 62 patients (47.3%) with classical mycosis fungoides, the majority were male (male : female = 4.2:1). There was one patient with Sézary syndrome. Patients aged older than 50 years were more likely to present with a longer duration of symptoms and advanced disease. In contrast to classical mycosis fungoides, the 47 patients diagnosed with hypopigmented mycosis fungoides had early stage disease, were younger, and no gender predilection was noted. The mean duration of follow up was 19.7 months (range 0.2-54.8 months). Complete remission was achieved in 24.7% and 53.8% of patients followed up at 1 and 3 years, respectively, using skin-directed and systemic treatment modalities appropriate for the stage of disease. There were five patients with progressive disease and three patients with advanced disease who died from disease-related complications. The most significant prognostic factors for 1-year and 3-year outcomes were the patient's duration of symptoms and stage of disease at presentation. PMID:17034466

  7. Full clinical recovery after topical acyclovir treatment of Epstein-Barr virus associated cutaneous B-cell lymphoma in patient with mycosis fungoides.

    PubMed

    Copur, M Sitki; Deshpande, Anita; Mleczko, Kris; Norvell, Max; Hrnicek, Gordon J; Woodward, Suzette; Frankforter, Scott; Mandolfo, Natalie; Fu, Kai; Chan, Wing C

    2005-06-01

    Primary cutaneous T- and B-cell lymphomas are a heterogeneous group of diseases with varied clinical presentations and prognosis. The use of new molecular, histological, and clinical criteria has improved their recognition. Cutaneous B-cell and T-cell lymphomas are seldom found together in the same patient. Here we report a rare case of mycosis fungoides variant of a cutaneous T-cell lymphoma (CTCL) which later developed Epstein-Barr virus (EBV) associated cutaneous B-cell lymphoproliferative disorder. The patient initially presented with generalized erythroderma, extensive plaques, and axillary lymphadenopathy. Histopathology and immunophenotyping of her tumor from the right breast nodule revealed a T-cell lymphoma consistent with mycosis fungoides. She was initially treated with pentostatin, followed by topical mechlorethamine and topical steroids. After progression of her mycosis fungoides with worsening diffuse skin lesions on this regimen, her treatments were changed to oral bexarotene with an initial partial response followed by stable disease. Three years from her initial presentation, she developed ulcerated cauliflower-like nodules on her forehead. Biopsy of these lesions revealed EBV-positive large- and medium-sized pleomorphic B-cells consistent with EBV-driven B-cell lymphoproliferative disorder. She was treated with topical acyclovir cream on the involved skin areas while continuing with oral bexarotene for mycosis fungoides. Skin lesions gradually diminished and totally disappeared after four weeks of topical acyclovir treatment. Bexarotene treatment was continued for another year until the mycosis fungoides progressed and became wide spread causing her death four and a half years after the initial diagnosis. The coexistence of two cutaneous non-Hodgkin lymphomas of different lineage in the same patient and the complete clinical response of EBV-related B-cell cutaneous component to topical acyclovir makes this rare case particularly interesting. PMID

  8. Cell Surface Differentiation Antigens of the Malignant T Cell in Sezary Syndrome and Mycosis Fungoides

    PubMed Central

    Haynes, Barton F.; Bunn, Paul; Mann, Dean; Thomas, Charles; Eisenbarth, George S.; Minna, John; Fauci, Anthony S.

    1981-01-01

    Using a panel of monoclonal antibodies and rabbit heteroantisera, we have studied the cell surface markers of peripheral blood (PB) Sezary cells from six patients with mycosis fungoides or Sezary syndrome, disease grouped within the spectrum of cutaneous T cell lymphomas (CTCL). Furthermore, we have studied two cell lines (Hut 78 and Hut 102) derived from malignant Sezary T cells from CTCL patients. The monoclonal antibody 3A1 defines a major human PB T cell subset (85% of PB T cells) while the antigen defined by the monoclonal antibody 4F2 is present on a subset (70%) of activated PB T cells and on circulating PB monocytes. In contrast to normal subjects in whom 60-70% of circulating PB mononuclear cells were 3A1+ T cells, PB mononuclear cells from six CTCL patients studied had an average of only 10.6±3.2% 3A1+ T cells. Whereas 85% of E-rosette positive cells from normal individuals were 3A1+, virtually all E-rosette positive T cells from the Sezary patients were 3A1-. Two patients with high numbers of circulating Sezary T cells had both aneuploid and diploid PB T cell populations present; after separation of PB T cells into 3A1+ and 3A1- cell suspensions, all 3A1- cells were found to be aneuploid. In contrast to normal resting PB T cells which were 4F2-, all PB Sezary cells were 4F2+, suggesting a state of activation. The 3A1 antigen was on a variety of acute lymphoblastic leukemia T cell lines (HSB-2, RPMI-8402, MOLT4, CEM) but was absent on the Hut 78 and Hut 102 Sezary T cell lines. Using rabbit anti-human T and anti-human Ia (p23, 30) antisera, we found that all malignant Sezary PB cells tested were killed by anti-T cell antiserum plus complement but not by anti-Ia plus complement. In contrast, Sezary cell lines Hut 78 and 102, were killed by both anti-T cell antiserum and anti-Ia plus complement. Similar to 3A1- normal PB T cells, 3A1- Sezary PB T cells proliferated poorly to phytohemagglutinin and concanavalin A. However, 3A1- Sezary T cells were able to

  9. 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.

  10. Phenotypic Variation in Different Lesions of Mycosis Fungoides Biopsied Within a Short Period of Time From the Same Patient.

    PubMed

    Kash, Natalie; Massone, Cesare; Fink-Puches, Regina; Cerroni, Lorenzo

    2016-07-01

    Phenotypic variants of mycosis fungoides (MF) include mainly the expression of cytotoxic markers by neoplastic cells (either α/β or γ/δ cytotoxic). To manage the patient properly, distinction from other cutaneous cytotoxic natural killer/T-cell lymphomas is paramount. Particularly for cutaneous γ/δ T-cell lymphoma, distinction is often based on clinicopathologic correlation (presence of tumors at first diagnosis as opposed to patches only in MF). The authors report a case of cytotoxic MF characterized by expression of TCRγ in two of three biopsies performed within a time frame of 1 week. The patient presented with patches, plaques, and 1 tumor at the time of first diagnosis; thus, distinction from cutaneous γ/δ T-cell lymphoma was not possible on clinical grounds alone. The diagnosis of MF was established, thanks to the phenotypic variations revealed by the three biopsies, with 1 lacking expression of cytotoxic proteins (TIA-1 and granzyme B) and of TCRγ. This case shows the importance to perform several biopsies in cases of cutaneous lymphoma, as morphologic and phenotypic features are variable and information gathered from a single biopsy may result in a wrong diagnosis. PMID:26885605

  11. Hypopigmented interface T-cell dyscrasia: a form of cutaneous T-cell dyscrasia distinct from hypopigmented mycosis fungoides.

    PubMed

    Magro, Cynthia M; Hagen, Joshua W; Crowson, Arthur N; Liu, Yen Chen; Mihm, Martin; Drucker, Natalie M; Yassin, Aminah H

    2014-07-01

    Hypopigmentation in cutaneous T-cell lymphoproliferative disease should not always be equated with hypopigmented mycosis fungoides (MF). A form of hypopigmented pre-lymphomatous T-cell dyscrasia falling under the designation of the so-called hypopigmented interface variant of T-cell dyscrasia has recently been proposed. The aim of the present study was to establish hypopigmented interface T-cell dyscrasia as its own entity apart from other T-cell dyscrasias and MF using a patient case series. Twenty four cases of hypopigmented interface T-cell dyscrasia were identified in the dermatopathology database of Weill Medical College of Cornell University. There were 17 females and seven males (mean age, 36 years). In children and adolescents, the patients were most commonly of African American extraction. Truncal photo-protected areas manifesting as large solitary patches or multiple smaller macules were characteristic; disease progression to MF occurred in only one patient. The lesions responded to topical steroids and light therapy. The pathology was defined by a cell poor interface associated with degeneration of keratinocytes and melanocytes, and by lymphocytes whose nuclei showed low-grade cerebriform atypia, and which expressed a significant reduction in CD7 and CD62L expression. In 50% of the cases, the implicated cell type was of the CD8 subset. Clonality was not identified. Hypopigmented interface T-cell dyscrasia is a distinct entity separate from and rarely progressive to MF. PMID:24806661

  12. Review of the treatment of mycosis fungoides and Sézary syndrome: A stage-based approach

    PubMed Central

    AL Hothali, Ghadah I.

    2013-01-01

    Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common subtypes of cutaneous T-cell lymphomas. Most of patients have indolent and incurable course of disease. Therefore, treatment should be reaching the optimal benefit with minimizing the toxicity as much as possible. To achieve this aim, the management should follow a -stage-based-approach. Treatment of early-stage MF (IA–IIA) involves skin-directed therapy (SDT) including topical corticosteroids, phototherapy, topical chemotherapy, topical retinoids and radiotherapy. For aggressive/recalcitrant early-stage MF or advanced-stage MF, systemic therapy should be considered including interferone-alpha, oral retinoids including bexarotine and more recently acitretin, histone deacetylase inhibitors (HDACi), fusion toxin denileukin diftitox and chemotherapy drugs. Combined drug regimens can be considered in some situations to get the synergistic effect while lowering the individual drug’s doses on the other hand. By exception of aggressive stages, chemotherapy should always come after other systemic drugs have been tried or contraindicated. Novel drugs should be considered in situations when all systemic drugs have failed. PMID:24421750

  13. 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

  14. New insights into associated co-morbidities in patients with cutaneous T-cell lymphoma (mycosis fungoides).

    PubMed

    Hodak, Emmilia; Lessin, Stuart; Friedland, Rivka; Freud, Tamar; David, Michael; Pavlovsky, Lev; Shapiro, Jonathan; Cohen, Arnon D

    2013-07-01

    Studies of associated cancer in patients with mycosis fungoides (MF) have focused primarily on secondary cancers in North American and European populations. This study investigated the association between MF and malignancies, anxiety and depression in the Israeli population. Data on Israeli patients with MF and age- and gender-matched controls were collected from a database of population- based cohort (683 patients; 1,700 controls) and an institution- based cohort (343 patients; 846 controls) and analysed by univariate and multivariate methods. MF was significantly associated with Hodgkin's lymphoma in both cohorts (multivariate odds ratio (OR) 7.83, univariate OR ∞, respectively); acute leukaemia (multivariate OR 10.1, first cohort) and lung cancer (multivariate OR 10.15, second cohort). MF was significantly associated with anxiety and depression (multivariate OR 1.59, OR 1.51, respectively in first cohort). The current study provides support to the associations between MF and other cancers: Hodgkin's lymphoma, acute leukaemia and lung cancer. The study also emphasizes the association between MF and anxiety and depression. PMID:23303582

  15. 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

  16. 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

  17. Long term outcomes of 1263 patients with Mycosis fungoides and Sézary syndrome from 1982 to 2009

    PubMed Central

    Talpur, Rakhshandra; Singh, Lotika; Daulat, Seema; Liu, Ping; Seyfer, Sarah; Trynosky, Tanya; Wei, Wei; Duvic, Madeleine

    2013-01-01

    Purpose The purpose of this prospectively collected single center study cohort of MF/SS 1263 patients is to evaluate the significance of stage and risk of disease progression from initial presentation, and to examine other prognostic factors. Patients and Methods The prognostic variables effecting overall survival (OS) were examined in a unique prospective cohort of 1263 mycosis fungoides (MF) and Sézary Syndrome (SS) patients seen by one investigator at MD Anderson Cancer Center from 1982–2009. Kaplan and Meier estimates were used to determine median overall survival (OS), progression-free survival (PFS) and disease specific survival (DSS). Cox’s proportional hazards regression model assessed prognostic factors. Results Mean age at diagnosis was 55.33 years. Early MF (Stage IA-IIA) represented 71.5% (903 of 1263) and advanced (Stage IIB–IVB), 28.5% (360 of 1263) patients. Progression to a higher stage occurred in 147 patients (11.6 %) of whom 112 (12%) were early and 35 (9.7%) advanced. Death from disease occurred in 102/1263 (8.1%) patients. Median OS was 24.44 years, PFS was 16 years, and median DSS was not reached. OS and PFS were significantly better for early stage patients with patches (T1a/T2a) than with patches/plaques (T1b/T2b). PFS analyzed in 1241 patients found only 337 (27.2%) had disease progression or had died from disease. Risk factors associated with progression or deaths were advanced age, plaque stage, LDH level, and tumor area. Conclusions Improved outcome of MF/SS, reflected by overall survival and PFS for all stages, may result from earlier diagnosis, new therapies, and aggressive treatment of infections. PMID:22850569

  18. Serum Vitamin D and Vitamin D Receptor Gene Polymorphism in Mycosis Fungoides Patients: A Case Control Study

    PubMed Central

    Rasheed, Hoda; Hegazy, Rehab A.; Gawdat, Heba I.; Mehaney, Dina A.; Kamel, Marwa M.; Fawzy, Marwa M.; Nooh, Mohammed M.; Darwish, Hebatallah A.

    2016-01-01

    Background Vitamin D has been considered a key player in various malignancies including cutaneous cancers. To date, mycosis fungoides (MF) has been the least studied in relation to vitamin D. Furthermore, the vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) have not been tackled before in the context of MF, despite their incrimination in numerous diseases. Aim of study To assess the role of vitamin D in MF by measuring its serum level, and studying VDR SNPs (TaqI, BsmI, FokI) in different stages of MF. Patients and Methods 48 patients with various stages of MF, and 45 healthy controls were included. Complete history, full clinical examination and a five mm punch skin biopsy were performed to all recruited patients. Venous blood samples were withdrawn from both patients and controls to determine the serum vitamin D level and VDR gene polymorphisms. Results Serum vitamin D level was significantly lower in patients (5.3–33.7 nmol/L)] compared to controls (8.3–90.1 nmol/L)] (P<0.001). A significant difference was observed between patients and controls regarding the FokI polymorphism only, being higher in patients (P = 0.039). Also Vitamin D serum levels differed significantly in patients with FokI genotypes (P = 0.014). No significant correlations were detected between any of the studied parameters and the demographic and clinical data of the included subjects. Conclusion Depressed vitamin D and FokI polymorphism are potentially involved in the context of MF. VDR gene polymorphisms warrant further larger scale investigations to detect the exact genes involved in the pathogenesis of such an enigmatic disease. PMID:27336155

  19. The current management of mycosis fungoides and Sézary syndrome and the role of radiotherapy: Principles and indications

    PubMed Central

    Mazzeo, Ercole; Rubino, Laura; Buglione, Michela; Antognoni, Paolo; Magrini, Stefano Maria; Bertoni, Francesco; Parmiggiani, Manuela; Barbieri, Paola; Bertoni, Filippo

    2013-01-01

    Aim To evaluate the current treatment of mycosis fungoides (MF) and Sézary syndrome (SS) focusing on the role of radiotherapy (RT), its principles and indications, and the perspectives of the novel irradiation technologies. Background MF and SS are rare lymphoproliferative diseases whose incidence is increasing. For a long time RT has been used as a single modality or in integrated treatment programs for these diseases. Materials and methods The latest systematic reviews, primary studies and new diagnostic and treatment guidelines on MF and SS were analyzed. Clinical outcomes together with the technical aspects and the role of RT were also evaluated. Results New data are available on pathogenesis, diagnostic criteria, classification and staging procedures for MF and SS and several local and systemic therapies are proposed. Localized RT can cure “minimal stage” MF while total skin electron beam irradiation (TSEI) may cure initial-stage disease and may offer important symptom relief (itch, erythroderma) in a more advanced setting. Despite its efficacy, RT is not largely used, mainly because of some technical difficulties but new RT technologies may be proposed to treat large skin surfaces. Conclusions New treatment programs offer good results, with median survival of more than 12 years in early-stage MF, but the median survival of 2.5 years or less in advanced stages is still a challenge. RT remains an option for all stages with a good cost/effectiveness ratio in a curative or palliative setting. New RT technologies can overcome some technical problems of treating large skin surfaces. PMID:24936325

  20. Consequences of p16 tumor suppressor gene inactivation in mycosis fungoides and Sézary syndrome and role of the bmi-1 and ras oncogenes in disease progression.

    PubMed

    Zhang, Chunlei; Toulev, Albena; Kamarashev, Jivko; Qin, Jian-Zhong; Dummer, Reinhard; Döbbeling, Udo

    2007-07-01

    In examining the expression of oncogenes and tumor suppressor genes in mycosis fungoides and Sézary syndrome, we found the cell cycle-regulating protein p16 to be absent in T cells. Immunohistochemical staining with p16-specific antibodies showed that the number of p16-expressing cells in cutaneous lesions decreases in late stages. The repression of p16 was not attributable to deletion or methylation of this gene; however, the Bmi-1 oncogene, a known suppressor of p16, was present in mycosis fungoides and Sézary syndrome cell lines and skin lesions. The absence of p16 correlated with the phosphorylation of the retinoblastoma protein on cyclin D/CDK4- or cyclin D/CDK6-specific sites. Ki-ras, which stimulates phosphorylation of retinoblastoma via cyclin-dependent kinases, was found in all tested cutaneous T-cell lymphoma samples; and its expression generally was stronger in advanced stages. Thus, cutaneous T-cell lymphoma cells show changes in oncogene and tumor suppressor gene expression that increase proliferation. PMID:17442375

  1. Array-based comparative genomic hybridization in early-stage mycosis fungoides: recurrent deletion of tumor suppressor genes BCL7A, SMAC/DIABLO, and RHOF.

    PubMed

    Carbone, Angelo; Bernardini, Laura; Valenzano, Francesco; Bottillo, Irene; De Simone, Clara; Capizzi, Rodolfo; Capalbo, Anna; Romano, Francesca; Novelli, Antonio; Dallapiccola, Bruno; Amerio, Pierluigi

    2008-12-01

    The etiology of mycosis fungoides (MF), the most frequent form of cutaneous T cell lymphoma (CTCL), is poorly understood. No specific genetic aberration has been detected, especially in early-stage disease, possibly due to the clinical and histological heterogeneity of patient series and to the different sources of malignant cells (skin, blood, or lymph node) included in most studies. Frozen skin biopsies from 16 patients with early-stage MF were studied using array-based comparative genomic hybridization. A DNA pool from healthy donors was used as the reference. Results demonstrated recurrent loss of 19, 7p22.1-p22.3, 7q11.1-q11.23, 9q34.12, 12q24.31, and 16q22.3-q23.1, and gain of 8q22.3-q23.1 and 21q22.12. The 12q24.31 region was recurrently deleted in 7/16 patients. Real-time PCR investigation for deletion of genes BCL7A, SMAC/DIABLO, and RHOF-three tumor suppressor genes with a putative role in hematological malignancies-demonstrated that they were deleted in 9, 10, and 13 cases, respectively. The identified genomic alterations and individual genes could yield important insights into the early steps of MF pathogenesis. PMID:18663754

  2. Prognostic factors in primary cutaneous lymphomas other than mycosis fungoides and the Sézary syndrome. The French Study Group on Cutaneous Lymphomas.

    PubMed

    Grange, F; Hedelin, G; Joly, P; Beylot-Barry, M; D'Incan, M; Delaunay, M; Vaillant, L; Avril, M F; Bosq, J; Wechsler, J; Dalac, S; Grosieux, C; Franck, N; Esteve, E; Michel, C; Bodemer, C; Vergier, B; Laroche, L; Bagot, M

    1999-06-01

    Prognostic studies of primary cutaneous lymphomas (PCL) other than mycosis fungoides (MF) and the Sézary syndrome (SS; non-MF/SS PCL) have been mainly performed on subgroups or on small numbers of patients by using univariate analyses. Our aim was to identify independent prognostic factors in a large series of patients with non-MF/SS PCL. We evaluated 158 patients who were registered in the French Study Group on Cutaneous Lymphomas database from January 1, 1986 to March 1, 1997. Variables analyzed for prognostic value were: age; sex; type of clinical lesions; maximum diameter, location, and number of skin lesions; cutaneous distribution (ie, local, regional, or generalized); prognostic group according to the European Organization for Research and Treatment of Cancer (EORTC) classification for PCL; B- or T-cell phenotype; serum lactate dehydrogenase (LDH) level; and B symptoms. Univariate and multivariate analyses were performed using a model of relative survival. Forty-nine patients (31%) died. The median relative survival time was 81 months. In univariate analysis, EORTC prognostic group, serum LDH level, B symptoms, and variables related to tumor extension (ie, distribution, maximum diameter, and number of skin lesions) were significantly associated with survival. When these variables were considered together in a multivariate analysis, EORTC prognostic group and distribution of skin lesions remained statistically significant, independent prognostic factors. This study confirms the good predictive value of the EORTC classification for PCL and shows that the distribution of skin lesions at initial evaluation is an important prognostic indicator. PMID:10339469

  3. Origin Use of CD4, CD8, and CD1a Immunostains in Distinguishing Mycosis Fungoides from its Inflammatory Mimics: A Pilot Study

    PubMed Central

    Tirumalae, Rajalakshmi; Panjwani, Poonam K

    2012-01-01

    Patch-stage/early mycosis fungoides (MF) is difficult to differentiate from benign dermatoses, despite several robust histologic criteria. Most studies include advanced lesions and data about early disease is limited. Objectives: (1) To compare the CD4:CD8 ratio in patch-stage MF versus inflammatory mimics. (2) To study patterns of CD1a expression in the epidermis and dermis in the two groups. Materials and Methods: Twenty cases each of early MF and inflammatory dermatoses were selected. The diagnoses were established after clinicopathologic correlation, repeat biopsies, and follow-up. The inflammatory group included pityriasis lichenoides chronica, actinic reticuloid, lichenoid purpura, and various psoriasiform dermatoses. Immunohistochemistry was done for CD4, CD8, and CD1a. Epidermal CD4, CD8 cells were quantified and CD1a was graded semi-quantitatively in the epidermis and dermis. Results: The average CD4:CD8 ratio was 4.2 in MF (range: 1-16.8), and 0.9 in inflammatory diseases (range: 0.43-5), which was statistically significant (P < 0.0001). None of the MF cases had a ratio <1. Four cases of pityriasis lichenoides chronica had a ratio >1. CD1a cells had a continuous or confluent epidermal pattern in almost all cases of MF, while they occurred as small or large groups in the dermis. In inflammatory dermatoses, there were either isolated or scattered CD1a+ cells in both epidermis and dermis. Conclusions: Elevated CD4:CD8 ratio favors MF. But there is an overlap in the lower range with pityriasis lichenoides chronica. These cases require good clinicopathologic correlation and follow-up. Patterns of CD1a expression are more reliable. Immunostains buttress morphology and are a valuable addition. PMID:23248358

  4. Interleukin-32 is progressively expressed in Mycosis Fungoides independent of helper T-cell 2 and helper T-cell 9 polarization

    PubMed Central

    Ohmatsu, Hanako; Humme, Daniel; Gulati, Nicholas; Gonzalez, Juana; Möbs, Markus; Suárez-Fariñas, Mayte; Cardinale, Irma; Mitsui, Hiroshi; Guttman-Yassky, Emma; Sterry, Wolfram; Krueger, James G.

    2014-01-01

    Mycosis Fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL) is characterized by a helper T cell 2 (Th2)-skewing with a mature CD4+ memory T-cell phenotype. Using skin samples from MF patients (n=21), healthy volunteers (n=17), individuals with atopic dermatitis (n=17) and psoriasis (n=9), we found interleukin (IL)-32 mRNA expression significantly higher in MF samples than in samples from benign inflammatory skin diseases, and its expression increases with disease progression. By immunohistochemistry and immunofluorescence, we confirmed IL-32 protein expression in many CD3+CD4+ T cells and some epidermotropic T cells in MF lesions. MyLa cells (a MF cell line) express IL-32, which in turn could promote cellular proliferation and viability in a dose-dependent fashion. IL-32-treated MyLa and CTCL HH cells up-regulated cell proliferation and survival genes. Of the major “polarizing” T-cell cytokines, only IFNγ mRNA increases with MF progression and positively correlates with IL-32 mRNA expression. Th2 cytokines do not positively correlate with IL-32 mRNA expression or MF progression. Furthermore, by flow cytometry, IL-32 production by circulating activated T-cells in healthy individuals was found in both IFNγ+ and IFNγ− cells but not in IL-4+ or IL-13+ cells. In conclusion, we have identified IL-32+ cells as the likely tumor cells in MF, and demonstrated that IL-32 mRNA expression increases with MF progression and is significantly higher than those in other skin diseases, and that some IL-32+ T cells are independent from the defined Th subsets. Thus IL-32 may play a unique role in MF progression as an autocrine cytokine. PMID:24938282

  5. 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

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

    PubMed Central

    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. PMID:26752418

  7. 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

  8. [Bone marrow biopsy in non-Hodgkin's lymphomas, chronic lymphoid leukemia and mycosis fungoides. 1. Incidence and infiltration patterns].

    PubMed

    Silva, M R; Mieza, M A; Saad, F A; Kerbauy, J; Burnier Júnior, M N

    1990-01-01

    Seventy bone marrow biopsies belonging to 53 patients with non-Hodgkin lymphomas, chronic lymphocytic leukemia, and micosis fungoides were studied. Bone marrow involvement was analyzed in correlation to staging before and after treatment. Bone marrow involvement was most frequently seen in CLL and IL followed by WDLL and PDLL/N and PDLL/D. Highest incidences after treatment were in CLL, WDLL, and PDLL/N and PDLL/D. With respect to staging, WDLL disseminated to bone marrow only in the late stages (III or IV), whereas the nodular and diffuse forms of PDLL presented similar infiltration in all stages. HLL and IL presented a slight trend to infiltrate only in the later stages. The pattern of bone marrow infiltration was also analyzed considering staging before and after treatment. No clear correlation was observed between staging and a specific pattern of bone marrow involvement in most cases, and disease evolution and treatment do not seem to change infiltration pattern. PMID:2287861

  9. 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

  10. Acquisition of CD30 and CD15 accompanied with simultaneous loss of all pan-T-cell antigens in a case of histological transformation of mycosis fungoides with involvement of regional lymph node: an immunophenotypic alteration resembling classical Hodgkin lymphoma.

    PubMed

    Reddi, Deepti M; Sebastian, Siby; Wang, Endi

    2015-03-01

    : Acquired expression of CD30 is frequently noted in histological transformation of mycosis fungoides (MF), but simultaneous gain of CD15 accompanied with loss of pan-T-cell antigens are extremely rare. We report an unusual case of transformed MF with such an immunophenotypic alteration resembling classical Hodgkin lymphoma. The patient was an 81-year-old male with MF, who was initially treated with topical steroids and phototherapy. Despite the initial response, the patient developed a tumor-like skin lesion that was confirmed to be CD30-positive large T-cell lymphoma and was subsequently found to have a regional lymph node involvement by pleomorphic large cell lymphoma. Besides CD30, pleomorphic large cells were positive for CD15 but negative for all B cell- and T cell-specific antigens. Epstein-Barr virus was negative. Polymerase chain reaction-based assays demonstrated a clonal rearrangement of T-cell receptor gamma gene but detected no B-cell clone. The mechanism and clinical significance of this phenotypic conversion remains to be elucidated. PMID:23612034

  11. 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

  12. 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

  13. Epidermolysis bullosa

    MedlinePlus

    ... is recommended for prospective parents who have a family history of any form of epidermolysis bullosa. During pregnancy, chorionic villus sampling to test the fetus is available. For couples at high risk of having a child with ...

  14. 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 ( ...

  15. 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 (bullae) that break open, ...

  16. Stages of Mycosis Fungoides and the Sezary Syndrome

    MedlinePlus

    ... following PDQ summaries: Adult Non-Hodgkin Lymphoma Treatment Skin Cancer Treatment Melanoma Treatment Kaposi Sarcoma Treatment A sign of ... or laser that directs UVB radiation at the skin. Chemotherapy Chemotherapy is a cancer treatment that uses drugs to stop the growth of ...

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

    MedlinePlus

    ... following PDQ summaries: Adult Non-Hodgkin Lymphoma Treatment Skin Cancer Treatment Melanoma Treatment Kaposi Sarcoma Treatment A sign of ... or laser that directs UVB radiation at the skin. Chemotherapy Chemotherapy is a cancer treatment that uses drugs to stop the growth of ...

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

    MedlinePlus

    ... following PDQ summaries: Adult Non-Hodgkin Lymphoma Treatment Skin Cancer Treatment Melanoma Treatment Kaposi Sarcoma Treatment A sign of ... or laser that directs UVB radiation at the skin. Chemotherapy Chemotherapy is a cancer treatment that uses drugs to stop the growth of ...

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

    MedlinePlus

    ... following PDQ summaries: Adult Non-Hodgkin Lymphoma Treatment Skin Cancer Treatment Melanoma Treatment Kaposi Sarcoma Treatment A sign of ... or laser that directs UVB radiation at the skin. Chemotherapy Chemotherapy is a cancer treatment that uses drugs to stop the growth of ...

  20. General Information about Mycosis Fungoides and the Sezary Syndrome

    MedlinePlus

    ... topical (put on the skin in a cream, lotion, or ointment ). The way the chemotherapy is given ... steroid . Topical corticosteroids may be in a cream, lotion, or ointment. Retinoids , such as bexarotene , are drugs ...

  1. 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 ( ...

  2. Concha bullosa: CT evaluation.

    PubMed

    Zinreich, S J; Mattox, D E; Kennedy, D W; Chisholm, H L; Diffley, D M; Rosenbaum, A E

    1988-01-01

    Aeration of the middle turbinate, termed "concha bullosa," is a common anatomical variant of intranasal anatomy. Of 320 patients evaluated for sinus disease with coronal CT, 34% had concha bullosa on at least one side. The overall incidence of inflammatory disease in the ostiomeatal complex in these symptomatic patients was not different between those with and without concha bullosa. However, there were many cases in which an abnormally large middle turbinate appeared to obstruct the ostiomeatal complex causing secondary infection of the ethmoid, frontal, and maxillary sinuses. Obstruction of drainage of the concha bullosa itself can lead to mucocele formation. Furthermore, the presence of a concha bullosa has important implications for the technique of endoscopic surgery used in the management of the sinus disease. The anatomy, pathophysiology, and CT findings in patients with concha bullosa are reviewed. PMID:3170840

  3. 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 (bullae) that break open, ...

  4. Myocosis fungoides--an update on a non-mycotic disease.

    PubMed

    Makdisi, Joy; Friedman, Adam

    2013-07-01

    Mycosis fungoides was first described in 1806 by the French physician Jean Louis Alibert in a patient whose skin lesions developed into mushroom-like tumors. Though it is not an infectious disease, it was termed mycosis fungoides (MF) due to its fungating appearance. In 1870, Bazin further described MF, proposing the three classical stages of the cutaneous disease: patch, plaque, and tumor. The term cutaneous T-cell lymphoma (CTCL) was first utilized in 1975 by Lutzner et al to describe a group of malignant infiltrative disorders of the skin including MF and Sézary syndrome. CTCLs comprise a spectrum of extranodal non-Hodgkin's lymphomas that are characterized by primary cutaneous involvement of a dominant clonal T-cell. As molecular biology and immunohistochemistry techniques have become more developed, CTCL has become understood to be a heterogeneous assembly of disorders that vary with regards to clinical course, histopathology, therapeutic considerations, and prognosis. MF, a low-grade lymphoproliferative disorder, is the most common type of CTCL, comprising 54% of CTCLs. It is a rare, extranodal, non-Hodgkin's lymphoma and is an epidermotropic neoplasm composed of CD4+ (helper) lymphocytes Sézary syndrome is a related leukemic subtype of CTCL that presents with diffuse skin involvement as well as circulating tumor cells in the peripheral blood. PMID:23884501

  5. 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 | ...

  6. Epidermolysis bullosa acquisita.

    PubMed

    Kim, J H; Kim, S-C

    2013-10-01

    Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune subepidermal bullous disease with clinical features similar to the genetic form of dystrophic epidermolysis bullosa. EBA is characterized by the presence of autoantibodies against type VII collagen which is a major component of the anchoring fibrils at the dermal-epidermal junction. EBA can be divided into two main clinical types; mechanobullous and inflammatory EBA. Mechanobullous EBA, referred to as classic EBA, presents with skin fragility, blisters and dystrophic changes on trauma-prone areas. Inflammatory EBA resembles other autoimmune subepidermal bullous diseases. Compelling evidence from mouse models supports a pathogenic role of autoantibodies against type VII collagen in EBA. Treatment of EBA is often unsatisfactory. The most widely used systemic treatment is corticosteroids. Colchicine and dapsone have been reported to be good treatment modalities when combined with corticosteroids. Some intractable cases of EBA have successfully been treated with intravenous immunoglobulin or rituximab. PMID:23368767

  7. Anesthesia and epidermolysis bullosa.

    PubMed

    Nandi, Reema; Howard, Richard

    2010-04-01

    Patients with epidermolysis bullosa (EB) may present for anesthesia with an unrelated surgical condition or, more commonly, for diagnostic or therapeutic procedures. Children in particular may require frequent anesthetics. Safe and effective management of anesthesia presents a significant challenge and although there is little rigorous evidence available to aid decision-making, in this article the elements of current good anesthesia care in EB are summarized. PMID:20447497

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

    ClinicalTrials.gov

    2016-04-11

    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

  9. Herlitz junctional epidermolysis bullosa.

    PubMed

    Laimer, Martin; Lanschuetzer, Christoph M; Diem, Anja; Bauer, Johann W

    2010-01-01

    Junctional epidermolysis bullosa type Herlitz (JEB-H) is the autosomal recessively inherited, more severe variant of "lucidolytic" JEB. Characterized by generalized, extensive mucocutaneous blistering at birth and early lethality, this devastating condition is most often caused by homozygous null mutations in the genes LAMA3, LAMB3, or LAMC2, each encoding for 1 of the 3 chains of the heterotrimer laminin-332. The JEB-H subtype usually presents as a severe and clinically diverse variant of the EB group of mechanobullous genodermatoses. This article outlines the epidemiology, presentation, and diagnosis of JEB-H. Morbidity and mortality are high, necessitating optimized protocols for early (including prenatal) diagnosis and palliative care. Gene therapy remains the most promising perspective. PMID:19945616

  10. Predictors of response to extracorporeal photopheresis in advanced mycosis fungoides and Sézary syndrome

    PubMed Central

    McGirt, Laura Y.; Thoburn, Christopher; Hess, Allan; Vonderheid, Eric C.

    2013-01-01

    Summary Background Extracorporeal photopheresis (ECP) has been utilized for more than 20 years to treat cutaneous T-cell lymphoma (CTCL), but a clinical response can take up to 9 months to manifest. This study was undertaken to determine whether clinical features, laboratory values, cytokine levels, or gene expression levels of tumor markers are useful to predict the subsequent response to ECP in CTCL patients with blood involvement. Methods Twenty-one patients with CTCL treated with ECP as monotherapy for at least 6 months were retrospectively identified. Laboratory and clinical data and blood obtained at baseline, 3, and 6 months of treatment were used for analysis. Results In pretreatment blood specimens, a lower percentage of Sézary cells and a higher absolute eosinophil count were associated with a favorable clinical response. Clinical evidence of an early response after 3 months of ECP did not reliably predict a favorable response at 6 months or beyond. Comparison of cytokines, gene transcripts, and other laboratory measures of disease did not correlate with the subsequent clinical response, although lactate dehydrogenase levels tended to decrease progressively in ECP-responsive cases and increase progressively in ECP-non-responsive cases. Additionally, serum levels of TNF-α significantly increased from baseline to 6 months of ECP, but was not found to correlate with the clinical response. Conclusions Although we found that increased eosinophils and decreased percentage of Sézary cells were associated with a favorable clinical response to ECP, we were not able to identify the predictors of ECP response within the first 3 months of treatment. PMID:20626820

  11. 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

  12. 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

  13. 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

  14. Anesthetic consideration in dystrophic epidermolysis bullosa

    PubMed Central

    Narejo, AS; Khan, MU; Alotaibi, WM; Khan, MM

    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. PMID:26955322

  15. Guttural pouch mycosis in a 6-month-old filly

    PubMed Central

    2006-01-01

    Abstract A 6-month-old filly was presented with unilateral epistaxis. Based on clinical signs, endoscopic examination, and postmortem examination, guttural pouch mycosis was diagnosed. The young age of the filly and the fact that this was the 2nd diagnosis of guttural pouch mycosis on this farm was unusual. PMID:16604984

  16. 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. PMID:15575565

  17. 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. PMID:27564298

  18. Metaplastic Conditions in The Bladder in Patient With Epidermolysis Bullosa

    PubMed Central

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

    2016-01-01

    ABSTRACT Epidermolysis bullosa is a rare inherited muco-cutaneous disorder that sometimes presents 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. PMID:27564298

  19. 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

  20. Nutrition for children with epidermolysis bullosa.

    PubMed

    Haynes, Lesley

    2010-04-01

    Optimization of resistance to infection, growth, sexual maturation, wound healing, and provision of the best possible overall quality of life are important management goals in children with epidermolysis bullosa. However, all these goals rely on the maintenance of optimal nutritional status, and achieving this is extremely challenging in the severe types of the disease. Strategies to improve nutritional status have the best chance of success when the dietitian or nutritionist works as an integral member of the multidisciplinary team and is well informed of patients' situations, family dynamics, and prognoses. Even the best-coordinated dietetic interventions may exert only limited impact. PMID:20447494

  1. 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

  2. Genetics Home Reference: epidermolysis bullosa with pyloric atresia

    MedlinePlus

    ... science of epidermolysis bullosa and diagnostic and molecular characterization: Proceedings of the IInd International Symposium on Epidermolysis ... Published : August 2, 2016 The resources on this site should not be used as a substitute for ...

  3. 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

  4. 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. PMID:25950805

  5. 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

  6. [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. PMID:27056851

  7. 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

  8. Laminin 332 in junctional epidermolysis bullosa.

    PubMed

    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

  9. Erythrodermia Congenitalis Ichthyosiformis Bullosa of Brocq

    PubMed Central

    Sander, Dorothea; Schröder, Josef; Schönbuchner, Ines; Schreml, Julia; Karrer, Sigrid; Berneburg, Mark; Schreml, Stephan

    2016-01-01

    A 50-year-old man presented with congenital scaling and hyperkeratosis on his palms, the soles of his feet and the extensor areas of his joints. The flexural areas were unaffected. His maternal grandmother, questionably his maternal uncle, his mother, all three brothers, one of his two sisters as well as two nephews and three nieces have or had similar skin changes. A punch biopsy was taken from the left palm. Clinical and histological signs led to the diagnosis of erythrodermia congenitalis ichthyosiformis bullosa of Brocq. We confirmed this genetically and found a heterozygous duplication (c.1752dupT) in the keratin 1 gene (KRT-1). To our knowledge, this is the first case of this skin condition reported in the literature with a heterozygous duplication (c.1752dupT) in KRT-1. PMID:26933410

  10. Clinical management for epidermolysis bullosa dystrophica.

    PubMed

    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

  11. 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

  12. 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. PMID:27149615

  13. 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

  14. 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. PMID:27126750

  15. Dental management of patients with epidermolysis bullosa.

    PubMed

    Dağ, Canan; Bezgin, Tuğba; Özalp, Nurhan

    2014-09-01

    Epidermolysis Bullosa (EB) is a group of rare, genetic skin disorders characterized by fragility and blistering to minimal trauma. All oral surfaces may be involved, including the tongue, buccal mucosa, palate, floor of the mouth and gingiva. Common oral findings of the disease include microstomia, intraoral ulcerations and bullae formation, ankyloglossia, tongue atrophy, elimination of buccal and vestibular sulci, lingual depapillation and atrophy of the palatal folds. In these case reports; systemic findings, oral manifestations and preventive measures are described for 3 patients with EB, all of whom required extensive oral management. Early dental management and preventive care to minimize caries development and improve oral health is very important for patients with EB. Pediatric dentists play an especially important role in early intervention. In describing the dental management of three EB cases, this article stresses the importance of an aggressive dental preventive programme with strict oral hygiene instructions for patients and parents along with frequent professional cleaning and fluoride therapy. PMID:25284524

  16. 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. PMID:27342035

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

    PubMed

    Kebbe, Jad; Mador, M Jeffery

    2016-07-01

    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

  18. 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

  19. Oral Manifestations and Dental Management of Epidermolysis Bullosa Simplex.

    PubMed

    Scheidt, Lisa; Sanabe, Mariane Emi; Diniz, Michele Baffi

    2015-01-01

    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

  20. 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

  1. Recently Identified Forms of Epidermolysis Bullosa.

    PubMed

    McGrath, John A

    2015-12-01

    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

  2. A Drosophila Model of Epidermolysis Bullosa Simplex.

    PubMed

    Bohnekamp, Jens; Cryderman, Diane E; Paululat, Achim; Baccam, Gabriel C; Wallrath, Lori L; Magin, Thomas M

    2015-08-01

    The blistering skin disorder epidermolysis bullosa simplex (EBS) results from dominant mutations in keratin 5 (K5) or keratin 14 (K14) genes, encoding the intermediate filament (IF) network of basal epidermal keratinocytes. The mechanisms governing keratin network formation and collapse due to EBS mutations remain incompletely understood. Drosophila lacks cytoplasmic IFs, providing a 'null' environment to examine the formation of keratin networks and determine mechanisms by which mutant keratins cause pathology. Here, we report that ubiquitous co-expression of transgenes encoding wild-type human K14 and K5 resulted in the formation of extensive keratin networks in Drosophila epithelial and non-epithelial tissues, causing no overt phenotype. Similar to mammalian cells, treatment of transgenic fly tissues with phosphatase inhibitors caused keratin network collapse, validating Drosophila as a genetic model system to investigate keratin dynamics. Co-expression of K5 and a K14(R125C) mutant that causes the most severe form of EBS resulted in widespread formation of EBS-like cytoplasmic keratin aggregates in epithelial and non-epithelial fly tissues. Expression of K14(R125C)/K5 caused semi-lethality; adult survivors developed wing blisters and were flightless due to a lack of intercellular adhesion during wing heart development. This Drosophila model of EBS is valuable for the identification of pathways altered by mutant keratins and for the development of EBS therapies. PMID:25830653

  3. 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

  4. 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…

  5. Epidermolysis bullosa pruriginosa: A report of two cases

    PubMed Central

    Pai, Varadraj Vasant; Sori, Tukaram; Naveen, Kikkeri Narayanshetty; Athanikar, Sharatchandra Bhimrao; Rai, Vijetha; Shastry, Dinesh Udupi

    2014-01-01

    Epidermolysis bullosa (EB) pruriginosa is a very rare pattern of dystrophic EB caused by type VII collagen gene mutation, with distinctive clinico-pathological features. It is characterized by nodular prurigo-like lichenified lesions, nail dystrophy, and variable presence of albopapuloid lesions. We report two such cases. PMID:24616855

  6. A concha bullosa mucopyocele manifesting as migraine headaches: a case report and literature review.

    PubMed

    Shihada, Rabia; Luntz, Michal

    2012-05-01

    A concha bullosa is a common anatomic variant that represents an aerated turbinate, usually the middle turbinate. It is usually asymptomatic. When extensively pneumatized, a large concha bullosa may cause significant problems, including headache, nasal obstruction, and blockage of sinus drainage. We report a case of a large concha bullosa mucopyocele that manifested as recurring migraine headaches. It was successfully treated with surgical excision. We also review the available literature. PMID:22614562

  7. 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.

  8. Analysis of differential β variable region of T cell receptor expression and NAV3/TNFRSF1B gene mutation in mycosis fungoides

    PubMed Central

    Li, Li; Ren, Jingyu; Guo, Shuping; Bai, Li

    2016-01-01

    Objective This study aimed to analyze the predominant expression of the variable region of T cell receptor (TRBV) and determine whether NAV3 or TNFRSF1B gene mutation involved in the pathogenesis of MF. Results TRBV5-7 expression increased from the normal, early-stage to advanced-stage lesion in MF patient. By contrast, TRBV2 decreased with the lesion developed. We found no mutations of NAV3 or TNFRSF1B in the lesions from this study. Materials and Methods Real-time PCR were used to screen differential expression of TRBV in different lesions. Mutational analyses were used to validate genetic alterations in the skin lesions. Conclusions The identification of TRBV gene expression differences between normal and different stages of MF lesions provide insight into promising new diagnostic and prognostic biomarkers. None of the reported genetic abnormalities suggests complexity of progress from a primary cytogenetic event to an advanced stage with poor prognosis in MF. PMID:26918607

  9. 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

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

    ClinicalTrials.gov

    2016-07-12

    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

  11. Restorative and periodontal challenges in adults with dystrophic epidermolysis bullosa.

    PubMed

    Puliyel, Divya; Chiu, Ching Hsiu Ketty; Habibian, Mina

    2014-05-01

    Oral manifestations of dystrophic epidermolysis bullosa (DEB) include blistering of the oral mucosa, scarring, limited mouth opening, decreased mobility of the tongue, restrictions in oral functions and a high incidence of caries. Adult oral health management is challenging and requires unique strategies, which have not been well described in the published literature. We present a case of DEB focusing on the obstacles encountered during restorative and periodontal care and recommendations for appropriate treatment. PMID:25087349

  12. Periodontal manifestation of epidermolysis bullosa: Looking through the lens

    PubMed Central

    Kudva, Praveen; Jain, Rajsi

    2016-01-01

    Epidermolysis bullosa (EB) is a genetic disease associated with fragility and bullous lesions of the skin and mucous membranes. There are various patterns of inheritance and histopathology. The disease is associated with systemic and oral manifestations. Treatment of this disease is multidisciplinary and remains only palliative till today. The present case report describes periodontal manifestations of EB and the treatment plan for the same. PMID:27041842

  13. Periodontal manifestation of epidermolysis bullosa: Looking through the lens.

    PubMed

    Kudva, Praveen; Jain, Rajsi

    2016-01-01

    Epidermolysis bullosa (EB) is a genetic disease associated with fragility and bullous lesions of the skin and mucous membranes. There are various patterns of inheritance and histopathology. The disease is associated with systemic and oral manifestations. Treatment of this disease is multidisciplinary and remains only palliative till today. The present case report describes periodontal manifestations of EB and the treatment plan for the same. PMID:27041842

  14. [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

  15. 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. PMID:24371728

  16. Innovative therapeutic strategies for recessive dystrophic epidermolysis bullosa.

    PubMed

    Larcher, F; Del Río, M

    2015-06-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is among the most serious rare skin diseases. It is also the rare skin disease for which most effort has been expended in developing advanced therapeutic interventions. RDEB is caused by collagen VII deficiency resulting from COL7A1 mutations. Therapeutic approaches seek to replenish collagen VII and thus restore dermal-epidermal adhesion. Therapeutic options under development include protein therapy and different cell-based and gene-based therapies. In addition to treating skin defects, some of these therapies may also target internal mucosa. In the coming years, these novel therapeutic approaches should substantially improve the quality of life of patients with RDEB. PMID:25796272

  17. Epidermolysis Bullosa Acquisita: From Pathophysiology to Novel Therapeutic Options.

    PubMed

    Kasperkiewicz, Michael; Sadik, Christian D; Bieber, Katja; Ibrahim, Saleh M; Manz, Rudolf A; Schmidt, Enno; Zillikens, Detlef; Ludwig, Ralf J

    2016-01-01

    Epidermolysis bullosa acquisita (EBA) is a prototypic organ-specific autoimmune disease induced by autoantibodies to type VII collagen causing mucocutaneous blisters. In the inflammatory (bullous pemphigoid-like) EBA variant, autoantibody binding is followed by a lesional inflammatory cell infiltration, and the overall clinical picture may be indistinguishable from that of bullous pemphigoid, the latter being the most common autoimmune bullous disease. The last decade witnessed the development of several mouse models of inflammatory EBA that facilitated the elucidation of the pathogenesis of autoantibody-induced, cell-mediated subepidermal blistering diseases and identified new therapeutic targets for these and possibly other autoantibody-driven disorders. PMID:26763420

  18. Management of oesophageal stenosis in epidermolysis bullosa dystrophica.

    PubMed Central

    Kern, I B; Eisenberg, M; Willis, S

    1989-01-01

    Seven patients with epidermolysis bullosa dystrophica and chronic and recurrent oesophageal lesions such as spasm, strictures, and complete occlusion were studied. Dysphagia could be cured with drugs if it was caused by bullae formation or spasm. If oesophageal strictures were present, endoscopy and bouginage with corticosteroid prophylaxis during the quiescent phase of the disease was a safe and useful procedure. We have also given corticosteroids, which reduced the oedema caused by bullae formation and oral phenytoin, which reduced epithelial detachment by inhibiting collagenase activity. Verapamil counteracted oesophageal spasm and pureed food during periods of dysphagia reduced blistering of the upper oesophagus. Images Fig 1 Fig 2 PMID:2751329

  19. Epidermolysis bullosa dystrophica treated with vitamin E and oral corticosteroids

    PubMed Central

    Unger, W. P.; Nethercott, J. R.

    1973-01-01

    A 12-year-old boy with histologically proved epidermolysis bullosa dystrophica was treated daily with 10,000 IU of DL-alphatocopheryl acetate and prednisone 120 mg. Comparison of a control study period of seven weeks with the period during which vitamin E was given revealed no significant improvement. The same negative results were noted with the use of prednisone although the levels believed necessary to produce improvement were never attained owing to supervening infection. ImagesFIG. 1FIG. 2 PMID:4704893

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

    PubMed

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

    2015-01-01

    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. PMID:26163555

  1. 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

  2. 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. PMID:26148662

  3. Oral manifestations of epidermolysis bullosa dystrophica: a rare genetic disease

    PubMed Central

    Parushetti, Anita Dundappa; Agrawal, Jiwanasha Manish; Nanjannawar, Lalita Girish; Agrawal, Manish Suresh

    2013-01-01

    Epidermolysis bullosa (EB) constitutes a group of phenotypically diverse genodermatoses, which manifests with blistering and erosions of the skin and mucous membranes as the unifying diagnostic feature. It is an acquired disease or inherited as either autosomal-dominant or recessive with an incidence of 1/50 000. The prominent clinical characteristic of the disease is the development of bullae or vesicles in mucosa or skin in response to minor trauma. It is a chronic mechanobullous disease characterised by auto antibodies against Type VII collagen. This paper documents a case of a man diagnosed with dominant dystrophic EB; describing the measures that dentists and healthcare providers should adopt in order to provide a safe and effective dental treatment. Early prevention protocols for these patients have also been discussed. PMID:23349175

  4. Epidermolysis bullosa, dental and anesthetic management: a case report.

    PubMed

    Esfahanizade, Katayoun; Mahdavi, Ali Reza; Ansari, Ghassem; Fallahinejad Ghajari, Masoud; Esfahanizadeh, Abdolreza

    2014-09-01

    Epidermolysis bullosa (EB) is a group of rare inherited skin and mucous membrane disorders in which blister formation may arise spontaneously or following a minor friction. Various patterns of inheritance are explicated for the disease. The disease has a profound effect on oral mucosa and may result in high prevalence of dental caries. General anesthesia is sometimes the only choice for dental treatments in patients with EB. The following case report describes the dental and anesthetic management of an 12.5 -year-old girl with dystrophic type of EB. The patient was followed up every 6 months. New carious lesions were detected one year after the treatment, on the last visit. Presenting a perfect dental care to children with this disorder can be challenging for the in charge specialist, both pediatric dentist and anesthesiologist. PMID:25191665

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

    PubMed

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

    2015-06-01

    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 been 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-based, umbilical cord blood-based and amniotic membrane-based therapies may play a role in the both the current and future treatment of RDEB. PMID:25795271

  6. 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. PMID:25816002

  7. 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

  8. Epidermolysis Bullosa, Dental and Anesthetic Management: A Case Report

    PubMed Central

    Esfahanizade, Katayoun; Mahdavi, Ali Reza; Ansari, Ghassem; Fallahinejad Ghajari, Masoud; Esfahanizadeh, Abdolreza

    2014-01-01

    Epidermolysis bullosa (EB) is a group of rare inherited skin and mucous membrane disorders in which blister formation may arise spontaneously or following a minor friction. Various patterns of inheritance are explicated for the disease. The disease has a profound effect on oral mucosa and may result in high prevalence of dental caries. General anesthesia is sometimes the only choice for dental treatments in patients with EB. The following case report describes the dental and anesthetic management of an 12.5 -year-old girl with dystrophic type of EB. The patient was followed up every 6 months. New carious lesions were detected one year after the treatment, on the last visit. Presenting a perfect dental care to children with this disorder can be challenging for the in charge specialist, both pediatric dentist and anesthesiologist. PMID:25191665

  9. Dental treatment in a patient with epidermolysis bullosa.

    PubMed

    Siqueira, Maria Alice; de Souza Silva, Juliana; Silva, Francisco Wanderley Garcia de Paula E; Díaz-Serrano, Kranya Victória; Freitas, Aldevina Campos de; Queiroz, Alexandra Mussolino de

    2008-01-01

    Epidermolysis bullosa (EB) is a rare inherited group of genodermatoses characterized by mucocutaneous fragility and blister formation, either spontaneously or as a result of minimal mechanical trauma. The repetition of these episodes in the oral cavity leads to atrophy of the mucosa, causing microstomia, ankyloglossia, tongue denudation, and vestibule obliteration, characteristics that make dental treatment difficult. Patients with EB are at high risk for caries due to the presence of dental anomalies; they also tend to have a soft diet and difficulties with mechanical removal of the dental biofilm. This case report presents a patient diagnosed with EB and describes the difficulties faced by the clinician during dental treatment as well as the measures adopted to safely manage the patient's dental care. PMID:18489655

  10. 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

  11. 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

  12. 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. PMID:26895535

  13. 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

  14. 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

  15. A patient with allergic bronchopulmonary mycosis caused by Aspergillus fumigatus and Candida albicans.

    PubMed

    Wardhana; Datau, E A

    2012-10-01

    Allergic Bronchopulmonary Mycosis (ABPM) is an exagregated immunologic response to fungal colonization in the lower airways. It may cause by many kinds of fungal, but Aspergillus fumigatus is the most common cause of ABPM, although other Aspergillus and other fungal organisms, like Candida albicans, have been implicated. Aspergllus fumigatus and Candida albicans may be found as outdoor and indoor fungi, and cause the sensitization, elicitation of the disease pathology, and its clinical manifestations. Several diagnostic procedurs may be impicated to support the diagnosis of ABPM caused by Aspergillus fumigatus and Candida albicans. A case of allergic bronchopulmonary mycosis caused by Aspergillus fumigatus and Candida albicans in a 48 year old man was discussed. The patient was treated with antifungal, corticosteroids, and antibiotic for the secondary bacterial infection. The patient's condition is improved without any significant side effects. PMID:23314973

  16. 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

  17. [Dental treatment in children with dystrophic form of epidermolysis bullosa].

    PubMed

    Korolenkova, M V

    2015-01-01

    The aim of the study was to summarize the experience for providing oral health care in children with epidermolysis bullosa (EB) treated in Central Research Institute of Dentistry and Maxillofacial Surgery in 2013-2014. Seven EB patients (5 female and 2 male aged 5-17) with dystrophic form of EB were included in the study. Oral status was recorded (oral hygiene, presence of enamel hypoplasia and intraoral soft tissue lesions). Dental treatment provided included teeth extractions under conscious sedation (6 cases), teeth treatment (both conventional and ART methods) (5 cases) and preventive program (5 cases). All 7 dystrophic EB patients presented with generalized enamel hypoplasia in both primary and permanent dentition. In these patients one should consider using non-adhesive face dressings and careful suction pipe positioning as well as applying liniments on cotton rolls not to cause both intraoral and extraoral soft tissue lesions. Sixteen milk teeth were extracted under conscious sedation, in 3 cases the procedure caused significant vestibular scarring. Twelve teeth were treated mostly by ART method (n=1 0) as limited mouth opening made conventional treatment impossible. Dental treatment in dystrophic EB is a real challenge for pediatric dentist. This group of patients requires a special dental rehabilitation plan as they present with generalized enamel hypoplasia and have significant risk of intraoral lesions. PMID:26145475

  18. 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

  19. 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

  20. 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

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

    PubMed

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

    2015-09-01

    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

  2. Loss of desmoplakin tail causes lethal acantholytic epidermolysis bullosa.

    PubMed

    Jonkman, Marcel F; Pasmooij, Anna M G; Pasmans, Suzanne G M A; van den Berg, Maarten P; Ter Horst, Henk J; Timmer, Albertus; Pas, Hendri H

    2005-10-01

    The cytoplasmic plaque protein desmoplakin (DP), which is located in desmosomes, plays a major role in epithelial and muscle cell adhesion by linking the transmembrane cadherins to the cytoplasmic intermediate filament network. Mutations of DP may cause striate palmoplantar keratoderma, arrhythmogenic right ventricular dysplasia, skin fragility/woolly hair syndrome, Naxos-like disease, and Carvajal syndrome. DP must be indispensable, because DP-/- mice are early abortive. Here, we report a patient with severe fragility of skin and mucous membranes caused by genetic truncation of the DP tail. The new phenotype is lethal in the neonatal period because of immense transcutaneous fluid loss. The phenotype also comprised universal alopecia, neonatal teeth, and nail loss. Histology showed suprabasal clefting and acantholysis throughout the spinous layer, mimicking pemphigus. Electron microscopy revealed disconnection of keratin intermediate filaments from desmosomes. Immunofluorescence staining of DP showed a distinct punctate intercellular pattern in the patient's skin. Protein analysis revealed expression of truncated DP polypeptides. Mutational analysis of the patient demonstrated compound heterozygosity for two DP mutations, 6079C-->T (R1934X) and 6370delTT, respectively. Aberrant mRNA transcripts that predict premature termination of translation with loss of the three intermediate filament-binding subdomains in the DP tail were detected by RT-PCR. The new dramatic phenotype, which we named "lethal acantholytic epidermolysis bullosa," underscores the paramount role of DP in epidermal integrity. PMID:16175511

  3. 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. PMID:19909967

  4. Colletotrichum gloeosporioides sensu lato causing deep soft tissue mycosis following a penetrating injury

    PubMed Central

    Figtree, Melanie; Weeks, Kerry; Chan, Leonie; Leyton, Arda; Bowes, Andrew; Giuffre, Bruno; Sullivan, Martin; Hudson, Bernard J

    2013-01-01

    Colletotrichum species have been rarely implicated in human disease. We describe a case of deep soft tissue mycosis following a penetrating injury with a lemon tree thorn. Direct Blankophor BA (Bayer) stain from intraoperative tissue showed fungal elements. Pure growth fungus was apparent at 2–4 days. Morphological features provisionally identified the isolate as a coelomycetous fungus, likely Colletotrichum species. This was confirmed with molecular analysis of the internal transcribed spacer region (ITS) region. PMID:24432213

  5. Management of cutaneous squamous cell carcinoma in patients with epidermolysis bullosa: best clinical practice guidelines.

    PubMed

    Mellerio, J E; Robertson, S J; Bernardis, C; Diem, A; Fine, J D; George, R; Goldberg, D; Halmos, G B; Harries, M; Jonkman, M F; Lucky, A; Martinez, A E; Maubec, E; Morris, S; Murrell, D F; Palisson, F; Pillay, E I; Robson, A; Salas-Alanis, J C; McGrath, J A

    2016-01-01

    This article summarizes recommendations reached following a systematic literature review and expert consensus on the diagnosis and management of cutaneous squamous cell carcinomas in people with epidermolysis bullosa. The guidelines are intended to help inform decision making by clinicians dealing with this complex complication of a devastating disease. PMID:26302137

  6. Vesicostomy as a Treatment Option for Epidermolisis Bullosa Case With Urethral and Meatal Involvement.

    PubMed

    Moradi, Mahmoudreza; Rezaee, Haress; Kaseb, Kaveh; Ebrahimi, Ali

    2016-07-01

    Epidermolisis Bullosa (EB) is a rare hereditary disorder that its junctional type is very rare one that involves epithelium, however, genitourinary epithelium involvement occurs so rarely. The present case is 5-year old boy; a known case of junctional EB whom had recurrent urinary retention due to meatal and urethral stenosis that was deteriorated by therapeutically interventions. PMID:27335789

  7. Clinical and molecular dilemmas in the diagnosis of familial epidermolysis bullosa pruriginosa.

    PubMed

    Ee, Hock Leong; Liu, Lu; Goh, Chee Leok; McGrath, John A

    2007-05-01

    Dystrophic epidermolysis bullosa is a rare and clinically heterogeneous mechanobullous disorder. One unusual clinical variant is epidermolysis bullosa pruriginosa (EBP), in which the combination of pruritus and skin fragility can lead to hypertrophic, lichenified nodules and plaques. This form of inherited epidermolysis bullosa may not develop clinically until adult life, leading to diagnostic confusion with acquired disorders, such as nodular prurigo, lichen simplex, lichen planus, hypertrophic scarring, or dermatitis artefacta. As in all other forms of dystrophic epidermolysis bullosa, the molecular pathology involves mutations in the gene encoding the anchoring fibril protein, type VII collagen (COL7A1), but there is no clear genotype-phenotype correlation in EBP. In this report, we describe a Chinese-Singaporean family with EBP in whom an autosomal dominant glycine substitution mutation, p.G2251E, was identified in exon 86 of the COL7A1 gene. This heterozygous mutation was identified in the genomic DNA of all 4 affected adults tested, as well as 2 clinically unaffected offspring (aged 9-29 years). Based on DNA sequencing, we predict that these individuals may develop EBP later in life, although additional factors leading to disease expression may determine phenotypic expression. Nevertheless, we plan to closely monitor these potentially presymptomatic individuals for symptoms of pruritus and early signs of the genetic disorder. PMID:17434045

  8. [Interdisciplinary care of newborns with epidermolysis bullosa and severe congenital ichthyoses].

    PubMed

    Ott, H; Guthmann, F; Ludwikowski, B

    2015-04-01

    Severe genodermatoses such as hereditary blistering diseases or Mendelian disorders of cornification may present as neonatal emergencies requiring interdisciplinary care. In particular, epidermolysis bullosa hereditaria, the collodion baby phenotype and harlequin ichthyosis represent serious clinical challenges with neonatal onset. This review summarizes dermatologically relevant aspects regarding pathogenesis, clinical presentation, diagnosis and therapy of these illnesses. PMID:25791506

  9. 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

  10. Mutation-based prenatal diagnosis of Herlitz junctional epidermolysis bullosa.

    PubMed

    Christiano, A M; Pulkkinen, L; McGrath, J A; Uitto, J

    1997-04-01

    Epidermolysis bullosa (EB) is a group of heritable diseases which manifest with blistering and erosions of the skin and mucous membranes. Due of life-threatening complications and significant long-term morbidity associated with the severe, neonatal lethal (Herlitz) form of junctional EB (H-JEB), there has been a demand for prenatal diagnosis from families at risk for recurrence. Previously, the only reliable method of prenatal diagnosis of EB was a fetal skin biopsy performed at 16-20 weeks' gestation and analysed by electron microscopy. Recently, the genes LAMA3, LAMB3, and LAMC2, encoding the polypeptide subunits of laminin 5, an anchoring filament protein, have been shown to contain mutations in H-JEB. In this study, direct detection of pathogenetic mutations in the laminin 5 genes was used to perform polymerase chain reaction (PCR)-based prenatal testing. DNA was obtained by chorionic villus sampling (CVS) at 10-15 weeks or amniocentesis at 12-19 weeks' gestation in 15 families at risk for recurrence of JEB. In 13 cases, the fetus was predicted to be either genetically normal or a clinically unaffected carrier of a mutation in one allele. These predictions have been validated in all cases by the birth of a healthy child. In two cases, an affected fetus was predicted, and the diagnosis was confirmed by subsequent fetal skin biopsy. These results demonstrate that DNA-based prenatal testing offers an early, expedient, and accurate method of prenatal diagnosis or an exclusion of Herlitz JEB. PMID:9160387

  11. [Cytoskeletal disorders in human keratinocytes--epidermolysis bullosa simplex].

    PubMed

    Kitajima, Y; Jokura, Y; Yaoita, H

    1991-06-01

    The cytoskeletons possibly related to pathogenesis in skin disease may be limited to keratin intermediate filaments (KIF) in epidermal keratinocytes. Keratins are divided into two subclasses; 11 acidic (type I) keratins and 8 basic (type II) keratins. Combination of equimolar amounts of type I and type II can form KIF. KIFs in human epidermal basal cells consist of a pair of type I and type II keratins specifically synthesized in the basal cells, and those in spinous cells contain two pairs of keratin; a pair of basal cell keratin and another pair of keratin specific for suprabasal cells. In the first section, molecular biology and differentiation of keratins are reviewed. In the second section, epidermolysis bullosa simplex (EBS) was introduced from the view point of abnormal organization of KIFs. In the epidermis of EBS, clefts are induced in the basal cells by minor trauma or frictions consequently to produce bullae. Electron microscopy reveals small spherical aggregations of tonofilaments (KIFs) in the basal cells. In biopsies, these KIF aggregations might be caused by artifacts during procedures for biopsies, so that, in order to avoid these artifacts, we studied the KIF organization in cultured keratinocytes from a patient by immunofluorescence using anti-keratin antibodies and electron microscopy. Anti-keratin antibodies revealed a formation of small droplet-like aggregations of KIFs in many cultured cells adhering to the culture bottles, which were also suggested by electron microscopy. From these observations, it is suggested that the abnormal organization (droplets) of KIFs might be one of intrinsic factors for the pathogenesis of EBS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1720328

  12. 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. PMID:25639865

  13. Mutation analysis and molecular genetics of epidermolysis bullosa.

    PubMed

    Pulkkinen, L; Uitto, J

    1999-02-01

    Cutaneous basement membrane zone (BMZ) consists of a number of attachment structures that are critical for stable association of the epidermis to the underlying dermis. These include hemidesmosomes, anchoring filaments and anchoring fibrils which form an interconnecting network extending from the intracellular milieu of basal keratinocytes across the dermal-epidermal basement membrane to the underlying dermis. Aberrations in this network structure, e.g. due to genetic lesions in the corresponding genes, can result in fragility of the skin at the level of the cutaneous BMZ. The prototype of such diseases is epidermolysis bullosa (EB), a heterogeneous group of genodermatoses characterized by fragility and blistering of the skin, often associated with extracutaneous manifestations, and inherited either in an autosomal dominant or autosomal recessive manner. Based on constellations of the phenotypic manifestations, severity of the disease, and the level of tissue separation within the cutaneous BMZ, EB has been divided into clinically distinct subcategories, including the simplex, hemidesmosomal, junctional and dystrophic variants. Elucidation of BMZ gene/protein systems and development of mutation detection strategies have allowed identification of mutations in 10 different BMZ genes which can explain the clinical heterogeneity of EB. These include mutations in the type VII collagen gene (COL7A1) in the dystrophic (severely scarring) forms of EB; mutations in the laminin 5 genes (LAMA3, LAMB3 and LAMC2) in a lethal (Herlitz) variant of junctional EB; aberrations in the type XVII collagen gene (COL17A1) in non-lethal forms of junctional EB; mutations in the alpha6 and beta4 integrin genes in a distinct hemidesmosomal variant of EB with congenital pyloric atresia; and mutations in the plectin gene (PLEC1) in a form of EB associated with late-onset muscular dystrophy. Identification of mutations in these gene/protein systems attests to their critical importance in the

  14. 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

  15. 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. PMID:23174001

  16. 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. PMID:26976809

  17. Alternative Use of an Oral Endotracheal Tube Fastener in a Patient with Junctional Epidermolysis Bullosa.

    PubMed

    Mummert, Lauren; Jones, James; Christopher, John

    2015-10-01

    This case report describes the alternative use of an oral endotracheal tube fastener in a pediatric patient with junctional epidermolysis bullosa. The patient underwent dental treatment in the operating room under general anesthesia and had a medical history of junctional epidermolysis bullosa, prior secondary anemia, clubbed feet, and past methicillin-resistant Staphylococcus aureus infection secondary to blistering. The oral endotracheal tube fastener was used in a nontraditional manner to avoid contact of the oral tube and tape with the epidermis and thus prevent blistering. Lubricated gauze was applied to the patient's eyes for protection, and lubricant was applied to the lips and perioral skin before intubation and during dental treatment. Postoperatively the patient exhibited minimal blistering secondary to intubation and dental treatment. PMID:26638453

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

    PubMed Central

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

    2013-01-01

    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. PMID:24379873

  19. 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. PMID:25498283

  20. 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. PMID:26046385

  1. 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

  2. [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. PMID:26943360

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

    PubMed Central

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

    2013-01-01

    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. PMID:23283611

  4. 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. PMID:22448522

  5. 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

  6. Comparison of superficial mycosis treatment using Butenafine and Bifonazole nitrate clinical efficacy.

    PubMed

    Abdul Bari, Mohammed A

    2013-01-01

    Superficial fungal infections are commonly encountered by the physician. And the continuously changing epidemiology of invasive fungal infections results in the need for an expanded armamentarium of antifungal therapies. This study was designed to evaluate the safety and efficacy of Butenafine (BTF) versus Bifonazole (BFZ) in the treatment of superficial mycosis in a randomized, double-blind, parallel-group trial. Of 96 patients, 48 applied (BTF) cream and 48 applied (BFZ) cream for 2 weeks to tinea versicolor, corporis and cruris treat, while tinea of feet & hands was treated for 4 weeks duration. Efficacy was assessed after the end of treatment and 2 weeks later. At the end of therapy, we find somewhat more patients using (BTF) than using (BFZ) had a mycologic cure ((BTF), 87.5%; (BFZ) 83.3%) and effective clinical response ((BTF), 91.7%; (BFZ), 83.3%). (BTF) provides rapid and persistent antifungal activity and symptom relief in patients with superficial mycosis during treatment. And patients continued to improve for at least 2 weeks after treatment. The Rates of mycologic cure and effective treatment with (BTF) were higher than with (BFZ) at cessation of treatment and 2 weeks later. However, no significant difference found between the two drugs (p> 0.05). PMID:23283047

  7. Comparison of Superficial Mycosis Treatment using Butenafine and Bifonazole nitrate Clinical Efficacy

    PubMed Central

    Bari, Mohammed A. Abdul

    2013-01-01

    Superficial fungal infections are commonly encountered by the physician. And the continuously changing epidemiology of invasive fungal infections results in the need for an expanded armamentarium of antifungal therapies. This study was designed to evaluate the safety and efficacy of Butenafine (BTF) versus Bifonazole (BFZ) in the treatment of superficial mycosis in a randomized, double-blind, parallel-group trial. Of 96 patients, 48 applied (BTF) cream and 48 applied (BFZ) cream for 2 weeks to tinea versicolor, corporis and cruris treat, while tinea of feet & hands was treated for 4 weeks duration. Efficacy was assessed after the end of treatment and 2 weeks later. At the end of therapy, we find somewhat more patients using (BTF) than using (BFZ) had a mycologic cure ((BTF), 87.5%; (BFZ) 83.3%) and effective clinical response ((BTF), 91.7%; (BFZ), 83.3%). (BTF) provides rapid and persistent antifungal activity and symptom relief in patients with superficial mycosis during treatment. And patients continued to improve for at least 2 weeks after treatment. The Rates of mycologic cure and effective treatment with (BTF) were higher than with (BFZ) at cessation of treatment and 2 weeks later. However, no significant difference found between the two drugs (p> 0.05). PMID:23283047

  8. 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

  9. Compound heterozygosity for nonsense ans missense mutations in the LAMB3 gene in nonlethal junctional epidermolysis bullosa.

    PubMed

    McGarth, J A; Christiano, A M; Pulkkinen, L; Eady, R A; Uitto, J

    1996-05-01

    Mutations in the genes encoding laminin 5 (LAMA3, LAMB3, and LAMC2) have been delineated in the autosomal recessive blistering skin disorder, junctional epidermolysis bullosa, particularly in the lethal (Herlitz) variant. In this study, we searched for mutations in these genes in two patients with nonlethal forms of junctional epidermolysis bullosa using polymerase chain reaction amplification of genomic DA, followed by heteroduplex analysis and direct automated nucleotide sequencing. Both patients were found to be compound heterozygotes for the same nonsense mutation on one LAMB3 allele, and different missense mutations on the other LAMB3 allele. The combination of a nonsense and a missense mutation in the LAMB3 gene appears to be important in determining the milder clinical phenotype in some cases of the nonlethal forms of junctional epidermolysis bullosa involving abnormalities in laminin 5. PMID:8618058

  10. Compound heterozygosity for nonsense and missense mutations in the LAMB3 gene in nonlethal junctional epidermolysis bullosa.

    PubMed

    Christiano, A M; Pulkkinen, L; Eady, R A; Uitto, J

    1996-04-01

    Mutations in the genes encoding laminin 5 (LAMA3, LAMB3, and LAMC2) have been delineated in the autosomal recessive blistering skin disorder, junctional epidermolysis bullosa, particularly in the lethal (Herlitz) variant. In this study, we searched for mutations in these genes in two patients with nonlethal forms of junctional epidermolysis bullosa using polymerase chain reaction amplification of genomic DNA, followed by heteroduplex analysis and direct automated nucleotide sequencing. Both patients were found to be compound heterozygotes for the same nonsense mutation on one LAMB3 allele, and different missense mutations on the other LAMB3 allele. The combination of nonsense and a missense mutation in the LAMB3 gene appears to be important in determining the milder clinical phenotype in some cases of the nonlethal forms of junctional epidermolysis bullosa involving abnormalities in laminin 5. PMID:8618020

  11. 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. PMID:26936632

  12. 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. PMID:26184962

  13. Rare case of subcutaneous mycosis with intrathoracic extension due to Chaetomium strumarium.

    PubMed

    Verma, R; Vasudevan, B; Badwal, S; Sriram, R; Neema, S; Kharayat, V

    2015-08-01

    A 47-year-old man presented with a 10-year history of multiple lumps over his left upper arm and shoulder and the adjoining left side of his chest and upper back. His medical history included diabetes mellitus type 2. The patient was a farmer and used to lift sacks of grains and fertilizers onto his shoulders as part of his work, although he did not recollect any history of specific trauma. Skin biopsy revealed granulomatous reaction with Splendore-Hoeppli phenomenon, while periodic-acid-Schiff and Grocott-Gomori stains confirmed fungal elements. Sabouraud agar grew Chaetomium species, and lactophenol blue mount confirmed the fungus as Chaetomium strumarium. Radiography and computed tomography of the chest revealed intrathoracic extension of the mycetoma. The patient responded well to treatment with oral Itraconazole. Subcutaneous mycosis due to C. strumarium is rarely reported in the literature, and the intrathoracic extension makes it an even rarer entity. PMID:25703412

  14. Exophiala angulospora Causes Systemic Mycosis in Atlantic Halibut: a Case Report.

    PubMed

    Overy, David P; Groman, David; Giles, Jan; Duffy, Stephanie; Rommens, Mellisa; Johnson, Gerald

    2015-03-01

    Filamentous black yeasts from the genus Exophiala are ubiquitous, opportunistic pathogens causing both superficial and systemic mycoses in warm- and cold-blooded animals. Infections by black yeasts have been reported relatively frequently in a variety of captive and farmed freshwater and marine fishes. In November 2012, moribund and recently dead, farm-raised Atlantic Halibut Hippoglossus hippoglossus were necropsied to determine the cause of death. Histopathology revealed that three of seven fish were affected by a combination of an ascending trans-ductual granulomatous mycotic nephritis, necrotizing histiocytic encephalitis, and in one fish the addition of a fibrogranulomatous submucosal branchitis. Microbial cultures of kidney using selective mycotic media revealed pure growth of a black-pigmenting septated agent. Application of molecular and phenotypic taxonomy methodologies determined that all three isolates were genetically consistent with Exophiala angulospora. This is the first report of E. angulospora as the causal agent of systemic mycosis in Atlantic Halibut. PMID:25496596

  15. Moderation of phenotypic severity in dystrophic and junctional forms of epidermolysis bullosa through in-frame skipping of exons containing non-sense or frameshift mutations.

    PubMed

    McGrath, J A; Ashton, G H; Mellerio, J E; Salas-Alanis, J C; Swensson, O; McMillan, J R; Eady, R A

    1999-09-01

    Non-sense mutations on both alleles of either the type VII collagen gene (COL7A1) or the genes encoding laminin 5 (LAMA3, LAMB3, or LAMC2) usually result in clinically severe forms of recessive dystrophic or junctional epidermolysis bullosa, respectively. In this study we assessed two unrelated families whose mutations in genomic DNA predicted severe recessive dystrophic epidermolysis bullosa or junctional epidermolysis bullosa phenotypes but in whom the manifestations were milder than expected. The recessive dystrophic epidermolysis bullosa patients had a homozygous single base-pair frameshift mutation in exon 19 of COL7A1 (2470insG). Clinically, there was generalized blistering but only mild scarring. Skin biopsy revealed positive type VII collagen immunoreactivity and recognizable anchoring fibrils. The junctional epidermolysis bullosa patients were compound heterozygotes for a frameshift/non-sense combination of mutations in exons 3 and 17 of LAMB3 (29insC/Q834X). These patients did not have the lethal form of junctional epidermolysis bullosa but, as adults, displayed the milder generalized atrophic benign epidermolysis bullosa variant. There was undetectable laminin 5 staining at the dermal-epidermal junction using an antibody to the beta3 chain, but faintly positive alpha3 and gamma2 chain labeling, and there was variable hypoplasia of hemidesmosomes. To explain the milder recessive dystrophic epidermolysis bullosa and junctional epidermolysis bullosa phenotypes in these families, reverse transcription-polymerase chain reaction, using RNA extracted from frozen skin, was able to provide evidence for some rescue of mutant mRNA transcripts with restoration of the open- reading frame. In the recessive dystrophic epidermolysis bullosa patients, transcripts containing in-frame skipping of exon 19 of COL7A1 in the cDNA were detected, and in the junctional epidermolysis bullosa patients transcripts with in-frame skipping of exon 17 of LAMB3 were identified. The

  16. Epidermolysis bullosa: Careful monitoring and no touch principle for anesthesia management

    PubMed Central

    Saraf, Sujit V; Mandawade, Nishigandha J; Gore, Sandeep K; Padhye, Usha D; Pereira, Charissa S

    2013-01-01

    Epidermolysis bullosa (EB) is a rare genetic mechanobullous disorder, with excessive fragility of the skin and mucous membranes. Avoiding mechanical injury to the skin and mucous membranes is essential in the anesthetic management. Shearing forces applied to the skin result in bullae formation, while compressive forces to the skin are tolerated. The challenge is to use monitoring technology without damaging the epithelial surface. Difficult airway, positioning issues, nutritional deficiencies, poor immunity, and carcinogenic potential add to the comorbidities. We managed a child with EB undergoing syndactyly release. Ensuring maximal skin and mucous membrane protection, anesthesia in children with EB can be conducted with few sequelae. PMID:24106369

  17. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome associated with neonatal epidermolysis bullosa acquisita.

    PubMed

    Bis, Sabina; Maguiness, Sheilagh M; Gellis, Stephen E; Schneider, Lynda C; Lee, Pui Y; Notarangelo, Luigi D; Keles, Sevgi; Chatila, Talal A; Schmidt, Birgitta A; Miller, Daniel D

    2015-01-01

    We report the case of a 2-week-old boy who presented with a vesiculopustular, bullous eruption in the setting of autoimmune enteropathy, hypothyroidism, membranous nephropathy, Coombs-positive hemolytic anemia, and persistent eosinophilia. Immunologic testing revealed a deficiency of FOXP3-expressing regulatory T cells, and a diagnosis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome was made. Histologic analysis, immunofluorescence, and enzyme-linked immunosorbent assay confirmed the bullous eruption as epidermolysis bullosa acquisita with associated collagen VII autoantibody production. The skin lesions responded to systemic immunosuppressant therapy and have regressed after allogeneic bone marrow transplantation. PMID:25790289

  18. A review of the obstetric management of patients with epidermolysis bullosa

    PubMed Central

    Bolt, L A; O'Sullivan, G; Rajasingham, D; Shennan, A

    2010-01-01

    Epidermolysis bullosa (EB) is a rare inherited skin condition characterized by the development of blisters after minor mechanical friction or trauma. There are few reported pregnancies in the literature in these women. We describe a pregnancy we recently managed. The collated series of pregnancies show that there are no additional antenatal or postnatal problems and that the skin itself does not worsen during pregnancy. Vaginal delivery is most favourable, but if a caesarean section is required, regional anaesthesia should be attempted. A multidisciplinary team should be active throughout the pregnancy of these women and a well-documented labour plan should be made in advance.

  19. Detection of novel LAMA3 mutation in Herlitz junctional epidermolysis bullosa in a Jordanian family.

    PubMed

    Badran, Eman F; Battah, Hamdi A; Akl, Kamal F; Khalil, Raida W; Al Amori, Iyad

    2013-08-01

    The Herlitz junctional epidermolysis bullosa (H-JEB) subtype usually presents as a severe lethal inherited variant of epidermolysis bullosa (EB) caused by a homozygous mutation in the genes LAMA3, LMAB3, or LAMAC3. Each gene encodes one of the three chains of heterotrimer laminin-332 proteins (including the alpha-3 chain, beta-3 chain and gamma-2-chain) responsible for the adherence of the epidermis to the underlying dermis. The aim of this report is to add to the existing knowledge about EB by describing a novel mutation in a gene responsible for genodermatosis. A case of a Jordanian male neonate, born to healthy, first cousin consanguineous parents, who developed nonhealing blistering skin and mucous membrane lesions, crusted erosions with significant granulation tissue and dystrophic nails immediately after birth is described. The patient was diagnosed as having a novel LAMA3 mutation causing (H-JEB) by immunofluorescence mapping and molecular analysis. Both parents and this baby's sibling were shown to be heterozygous carriers of the same mutation. Pre-implantation diagnosis using molecular analysis for subsequent pregnancies in this family is crucial for managing any new pregnancy. PMID:22963541

  20. 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. PMID:24170138

  1. 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. PMID:27212645

  2. 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. PMID:25678008

  3. Nexus between epidermolysis bullosa and transcriptional regulation by thyroid hormone in epidermal keratinocytes

    PubMed Central

    Tomic-Canic, Marjana; Stojadinovic, Olivera; Lee, Brian; Walsh, Rebecca; Blumenberg, Miroslav

    2014-01-01

    Thyroid hormone, T3, through the interaction of its receptor with the recognition sequences in the DNA, regulates gene expression. This regulation includes the promoter activity of keratin genes. The receptor shares co-regulators with other members of the nuclear receptor family, including RXR. Intending to define the transcriptional effects of thyroid hormones in keratinocytes, we used Affymetrix microarrays to comprehensively compare the genes expressed in T3 treated and untreated human epidermal keratinocytes. The transcriptomes were compared at 1, 4, 24, 48 and 72 hrs. Surprisingly, T3 induced only 9 and suppressed 28 genes, much fewer than expected. Significantly, genes associated with Epidermolysis bullosa, a set of inherited blistering skin diseases, were found statistically highly over-represented among the suppressed genes. These genes include Integrin β4, Plectin, Collagen XVII, MMP1, MMP3 and MMP14. The data imply that in keratinocytes T3 could suppresses the remodeling by, attachment to, and production of extracellular matrix. The results suggest that topical treatment with T3 may be effective for alleviation of symptoms in patients with Epidermolysis bullosa. PMID:20443817

  4. 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

  5. Allergic bronchopulmonary mycosis due to fungi other than Aspergillus: a global overview.

    PubMed

    Chowdhary, Anuradha; Agarwal, Kshitij; Kathuria, Shallu; Gaur, Shailendra Nath; Randhawa, Harbans Singh; Meis, Jacques F

    2014-02-01

    Allergic bronchopulmonary mycosis (ABPM) is a hypersensitivity-mediated disease of worldwide distribution. We reviewed 143 reported global cases of ABPM due to fungi other than aspergilli. The commonest etiologic agent was Candida albicans, reported in 60% of the cases, followed by Bipolaris species (13%), Schizophyllum commune (11%), Curvularia species (8%), Pseudallescheria boydii species complex (3%) and rarely, Alternaria alternata, Fusarium vasinfectum, Penicillium species, Cladosporium cladosporioides, Stemphylium languinosum, Rhizopus oryzae, C. glabrata, Saccharomyces cerevisiae and Trichosporon beigelii. India accounted for about 47% of the globally reported cases of ABPM, attributed predominantly to C. albicans, followed by Japan (16%) where S. commune predominates, and the remaining one-third from the USA, Australia and Europe. Notably, bronchial asthma was present in only 32% of ABPM cases whereas its association with development of allergic bronchopulmonary aspergillosis (ABPA) is known to be much more frequent. The cases reviewed herein revealed a median IgE value threefold higher than that of ABPA, suggesting that the etiologic agents of ABPM incite a stronger immunological response than that by aspergilli in ABPA. ABPM is currently underdiagnosed, warranting comprehensive basic and clinical studies in order to elucidate its epidemiology and to devise a more effective therapy. PMID:23383677

  6. 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. PMID:26465365

  7. Proinflammatory Cytokines and Antiskin Autoantibodies in Patients With Inherited Epidermolysis Bullosa

    PubMed Central

    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

    2015-01-01

    Abstract 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

  8. 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. PMID:26496255

  9. Cytoskeletal Regulation of Inflammation and Its Impact on Skin Blistering Disease Epidermolysis Bullosa Acquisita.

    PubMed

    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

  10. 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

  11. A novel LAMA3 mutation in a newborn with junctional epidermolysis bullosa herlitz type.

    PubMed

    Mazzucchelli, Iolanda; Garofoli, Francesca; Decembrino, Lidia; Castiglia, Daniele; Tadini, Gianluca; Bellingeri, Andrea; Borghesi, Alessandro; Tzialla, Chryssoula; Manzoni, Paolo; Stronati, Mauro

    2011-01-01

    The case of a male neonate of 41 weeks' gestation who developed blistering of the skin immediately after birth is described. His parents were consanguineous Tunisians. Electron microscopy of a cutaneous biopsy showed skin cleavage within the lamina lucida and immunoepitope mapping revealed a complete absence of laminin 332 expression. These findings referred to the diagnosis of junctional epidermolysis bullosa (JEB) Herlitz type. The neonate died at 3 months of age due to sepsis. Molecular analysis of laminin 332 chain genes LAMA3, LAMB3 and LAMC2 disclosed a novel homozygous nonsense mutation in LAMA3 (p.Y955X). Clinical and laboratory analyses are essential for the diagnosis of JEB subtypes, and molecular analysis screening is crucial to manage a new pregnancy in families with suspected cases of JEB. PMID:20881434

  12. Cross-reactivity of autoantibodies from patients with epidermolysis bullosa acquisita with murine collagen VII.

    PubMed

    Csorba, Kinga; Sesarman, Alina; Oswald, Eva; Feldrihan, Vasile; Fritsch, Anja; Hashimoto, Takashi; Sitaru, Cassian

    2010-04-01

    The pathomechanism of antibody-mediated tissue damage in autoimmune diseases can be best studied in experimental models by passively transferring specific autoantibodies into animals. The reproduction of the disease in animals depends on several factors, including the cross-reactivity of patient autoantibodies with the animal tissue. Here, we show that autoantibodies from patients with epidermolysis bullosa acquisita (EBA), a subepidermal autoimmune blistering disease, recognize multiple epitopes on murine collagen VII. Indirect immunofluorescence microscopy revealed that EBA patients' IgG cross-reacts with mouse skin. Overlapping, recombinant fragments of murine collagen VII were used to characterize the reactivity of EBA sera and to map the epitopes on the murine antigen by ELISA and immunoblotting. The patients' autoantibody binding to murine collagen VII triggered pathogenic events as demonstrated by a complement fixing and an ex vivo granulocyte-dependent dermal-epidermal separation assay. These findings should greatly facilitate the development of improved disease models and novel therapeutic strategies. PMID:20084423

  13. 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

  14. Gene editing toward the use of autologous therapies in recessive dystrophic epidermolysis bullosa.

    PubMed

    Perdoni, Christopher; Osborn, Mark J; Tolar, Jakub

    2016-02-01

    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 increased 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 next-generation treatments designed to correct the causative genetic defects of RDEB. PMID:26073463

  15. Newborn with severe epidermolysis bullosa: to treat or not to treat?

    PubMed

    Boesen, Martin Lehmann; Bygum, Anette; Hertz, Jens Michael; Zachariassen, Gitte

    2016-01-01

    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. PMID:27118747

  16. From marrow to matrix: novel gene and cell therapies for epidermolysis bullosa.

    PubMed

    Webber, Beau R; Tolar, Jakub

    2015-06-01

    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

  17. 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

  18. Abnormal organization of keratin intermediate filaments in cultured keratinocytes of epidermolysis bullosa simplex.

    PubMed

    Kitajima, Y; Inoue, S; Yaoita, H

    1989-01-01

    Distinctive abnormality in the organization of keratin intermediate filaments (KIFs) was found for the first time in cultured epidermal keratinocytes from two patients with hereditary epidermolysis bullosa simplex (EBS), which showed cleavages above the basement membrane zone due to the fragility of basal cells. KIFs in EBS keratinocytes revealed an irregular radial arrangement composed of sparse but thick KIF bundles. Furthermore, these KIF bundles in many cells changed into numerous ball-like keratin aggregates and disappeared beyond these keratin aggregates in the peripheral cytoplasm. Electron microscopy of cultured EBS keratinocytes showed that many ball-like structures consisting of fine filaments or granules or homogeneous substances were scattered in the peripheral regions of the cell attaching to the dish, and intermediate filaments appeared to be emanating from or surrounding the structures. These ball-like keratin aggregates have never been observed in normal human keratinocytes. PMID:2471468

  19. The Use of Cultured Allogenic Keratinocyte Grafting in a Patient with Epidermolysis Bullosa Simplex

    PubMed Central

    Shin, Kee Cheol; Park, Bo Young; Kim, Woo Seob; Bae, Tae Hui

    2011-01-01

    Epidermolysis bullosa (EB) is a rare genetic disease that is known for continuous skin blistering caused by minor trauma. The skin blisters and bullae that develop often cause skin defects. There is no definitive treatment for EB, only symptomatic relief. We report our experience with cultured allogenic keratinocyte grafting in a newborn patient with EB simplex who had unhealed raw surfaces and was not a skin grafting candidate. The skin lesions of the patient were covered with cultured allogenic keratinocyte grafts and re-epithelialized quickly with no scarring. Allogenic keratinocyte grafting reduced pain and produced noticeable improvements in the unhealed wounds. We think that allogenic keratinocyte grafting can play an important role in the management of patients with EB simplex. PMID:22346287

  20. 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

  1. Granulation tissue in the eyelid margin and conjunctiva in junctional epidermolysis bullosa with features of laryngo-onycho-cutaneous syndrome.

    PubMed

    Figueira, Edwin C; Crotty, Anne; Challinor, Christopher J; Coroneo, Minas T; Murrell, Dedee F

    2007-03-01

    Eye and adnexal involvement in epidermolysis bullosa can range from symptoms of mild irritation resulting from conjunctival involvement to severe cicatrization of the ocular surface and adnexa. We describe a unique case of granulation tissue in the eyelid margin and conjunctiva in a patient with junctional epidermolysis bullosa. The eyelid granulation tissue resembled granulomas that seen in laryngo-onycho-cutaneous syndrome, which is caused by a mutation in an isoform of the LAMA3 gene, LAMA3a. On investigation, our patient had a combination of a unique mutation in LAMA3 and the mutation I17N in LAMA3a, providing further evidence that laryngo-onycho-cutaneous syndrome is a variant of junctional EB. PMID:17362460

  2. Maternal uniparental meroisodisomy in the LAMB3 region of chromosome 1 results in lethal junctional epidermolysis bullosa.

    PubMed

    Takizawa, Y; Pulkkinen, L; Shimizu, H; Lin, L; Hagiwara, S; Nishikawa, T; Uitto, J

    1998-05-01

    Herlitz junctional epidermolysis bullosa (OMIM#226700) is a lethal, autosomal recessive blistering disorder caused by mutations in one of the three genes LAMA3, LAMB3, or LAMC2, encoding the constitutive polypeptide subunits of laminin 5. In this study, we describe a patient homozygous for a novel nonsense mutation Q936X in exon 19 of LAMB3, which has been mapped to chromosome 1q32. The patient was born with extensive blistering and demonstrated negative immunofluorescence staining for laminin 5, and transmission electron microscopy revealed tissue separation within lamina lucida of the dermal-epidermal junction, diagnostic of Herlitz junctional epidermolysis bullosa. The mother of the proband was found to be a heterozygous carrier for this mutation, whereas the father demonstrated the wild-type LAMB3 allele only. Nonpaternity was excluded by 13 microsatellite markers in six different chromosomes. Genotype analysis using 28 microsatellite markers spanning chromosome 1 revealed that the patient had maternal primary heterodisomy, as well as meroisodisomy within two regions of chromosome 1, one on 1p and the other one on 1q, the latter region containing the maternal LAMB3 mutation. These results suggest that Herlitz junctional epidermolysis bullosa in this patient developed as a result of reduction to homozygosity of the maternal LAMB3 mutation on chromosome 1q32. PMID:9579554

  3. Using a dermal skin substitute in the treatment of chronic wounds secondary to recessive dystrophic epidermolysis bullosa: a case series.

    PubMed

    Sibbald, R Gary; Zuker, Ron; Coutts, Patricia; Coelho, Sunita; Williamson, Diane; Queen, Douglas

    2005-11-01

    Epidermolysis bullosa is a family of genetic disorders that cause blistering and shearing of the skin from even the mildest trauma. Care generally focuses on preventing infection, protecting the skin against trauma, attending to nutritional deficiencies and dietary complications, minimizing deformities and contractures, and providing psychological support for the entire family. One approach to the treatment of chronic wounds in Epidermolysis bullosa involves tissue engineering, where cells similar to those of the skin, grown on a three-dimensional scaffold, are used to induce healing. Charts of six young people (ages 8 years to 23 years; four girls, two boys) with recessive dystrophic Epidermolysis bullosa who received applications of a dermal skin substitute to persistent erosions at multiple body sites (55) at successive clinic visits were reviewed. Each patient received between seven and 32 skin substitute applications to between six and 19 sites; patients were followed for at least 8 weeks. At weeks 1 to 2, epidermal coverage ranged between 80% and 100%. Some sites had persistent coverage but others experienced breakdown. Four patients had hand surgery and the living skin substitute was used postsurgically to provide coverage for the epidermal defects. Overall in these six cases, the dermal skin substitute proved advantageous to wound protection, healing, and symptom relief. Compassionate care combined with optimal wound care and advancing technology may offer an effective antidote to the wounding and pain of this devastating disease. PMID:16319445

  4. Bipolaris hawaiiensis as etiologic agent of allergic bronchopulmonary mycosis: first case in a paediatric patient.

    PubMed

    Chowdhary, Anuradha; Randhawa, Harbans S; Singh, Varinder; Khan, Z U; Ahmad, S; Kathuria, Shallu; Roy, P; Khanna, Geetika; Chandra, Jagdish

    2011-10-01

    Allergic bronchopulmonary mycosis (ABPM) is a worldwide hypersensitivity lung disease of multiple etiologies with Aspergillus fumigatus as the most common etiologic agent. We report the first instance of Bipolaris hawaiiensis causing ABPM in a paediatric patient. A six-year-old girl presented in June 2009 with productive cough, exertional dyspnoea, occasional wheezing, restricted air entry in left infra-scapular and infra-axillary areas, 7% eosinophils (absolute count 540/mm(3)) and total IgE 1051.3 IU/m in the sera. Bronchoscopy revealed narrowing of left main bronchus and mucoid impaction of the left lower lobe segmental bronchi. Cytological examination of BAL revealed few eosinophils, Charcot-Leyden crystals and mucus embedded hyphae. Examination of KOH wet mounts of repeated sputum and BAL specimens revealed septate, brownish hyphae and culture of the specimens resulted in the isolation of multiple colonies of a fungus later identified as B. hawaiiensis based on phenotypic characters and sequencing of internal transcribed spacer and D1/D2 regions of rDNA. In addition, (1-3)-β-D-glucan was demonstrated in serum (316 pg/ml) by Fungitell kit, supportive of fungal infection/colonization. Histopathologic studies of a bronchial biopsy revealed necrotic debris, macrophage aggregates, lymphocytes, polymorphs and PAS positive hypae. The patient was administered oral itraconazole for 12 weeks, intravenous liposomal amphotericin B for one month, weekly bronchoscopic suctioning and voriconazole instillation, resulting in reduced mucopurulent secretions and considerable clinical improvement. A serum sample collected on 5 November demonstrated precipitins against antigens of the B. hawaiiensis isolate. In March 2010, intradermal skin testing revealed a strong, type I hypersensitivity (induration diam-12 mm) against B. hawaiiensis. The patient relapsed with wheezing and difficulty in respiration in April 2010. Considering the positive type I cutaneous hypersensitivity, the

  5. Epidermolysis Bullosa

    MedlinePlus

    ... and swallowing food and drinks. If breast or bottle feeding results in blisters, infants may be fed ... mutations can be identified, doctors can identify ova (eggs) that do not contain an abnormal gene. These ...

  6. Epidermolysis bullosa

    MedlinePlus

    ... narrowing Repair of hand deformities Removal of any squamous cell carcinoma (a type of skin cancer) that develops OTHER TREATMENTS Other treatments for this condition may include: Medicines that suppress the immune system may be used ...

  7. Epidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ domain protein GRIP1

    PubMed Central

    Bladt, Friedhelm; Tafuri, Anna; Gelkop, Sigal; Langille, Lowell; Pawson, Tony

    2002-01-01

    Glutamate receptor-interacting protein 1 (GRIP1) is an adaptor protein composed of seven PDZ (postsynaptic density-95/Discs large/zona occludens-1) domains, capable of mediating diverse protein–protein interactions. GRIP1 has been implicated in the regulation of neuronal synaptic function, but its physiologic roles have not been defined in vivo. We find that elimination of murine GRIP1 results in embryonic lethality. GRIP1−/− embryos develop abnormalities of the dermo-epidermal junction, resulting in extensive skin blistering around day 12 of embryonic life. Ultra-structural characterization of the blisters (or bullae) revealed cleavage of the dermo-epidermal junction below the lamina densa, an alteration reminiscent of the dystrophic form of human epidermolysis bullosa. Blisters were also observed in the lateral ventricle of the brain and in the meninges covering the cerebral cortex. These genetic data suggest that the GRIP1 scaffolding protein is required for the formation and integrity of the dermo-epidermal junction and reveal the importance of PDZ domains in the organization of supramolecular structures essential for mammalian embryonic development. PMID:11983858

  8. 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.

  9. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells.

    PubMed

    Mavilio, Fulvio; Pellegrini, Graziella; Ferrari, Stefano; Di Nunzio, Francesca; Di Iorio, Enzo; Recchia, Alessandra; Maruggi, Giulietta; Ferrari, Giuliana; Provasi, Elena; Bonini, Chiara; Capurro, Sergio; Conti, Andrea; Magnoni, Cristina; Giannetti, Alberto; De Luca, Michele

    2006-12-01

    The continuous renewal of human epidermis is sustained by stem cells contained in the epidermal basal layer and in hair follicles. Cultured keratinocyte stem cells, known as holoclones, generate sheets of epithelium used to restore severe skin, mucosal and corneal defects. Mutations in genes encoding the basement membrane component laminin 5 (LAM5) cause junctional epidermolysis bullosa (JEB), a devastating and often fatal skin adhesion disorder. Epidermal stem cells from an adult patient affected by LAM5-beta3-deficient JEB were transduced with a retroviral vector expressing LAMB3 cDNA (encoding LAM5-beta3), and used to prepare genetically corrected cultured epidermal grafts. Nine grafts were transplanted onto surgically prepared regions of the patient's legs. Engraftment was complete after 8 d. Synthesis and proper assembly of normal levels of functional LAM5 were observed, together with the development of a firmly adherent epidermis that remained stable for the duration of the follow-up (1 year) in the absence of blisters, infections, inflammation or immune response. Retroviral integration site analysis indicated that the regenerated epidermis is maintained by a defined repertoire of transduced stem cells. These data show that ex vivo gene therapy of JEB is feasible and leads to full functional correction of the disease. PMID:17115047

  10. Case report: rapidly healing epidermolysis bullosa wound after ablative fractional resurfacing.

    PubMed

    Krakowski, Andrew C; Ghasri, Pedram

    2015-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating genodermatosis characterized by generalized skin fragility, severe blistering, and wounding that heals with mutilating scarring. Patients are in constant need of effective wound therapies as they often succumb to aggressive metastatic squamous cell carcinomas or to sepsis that may develop from their chronic wounds. Herein, we demonstrate accelerated wound healing with use of a fractionated CO2 laser protocol in a 22-year-old man with RDEB. His 9-month-old, non-healing wound decreased from 7 cm in diameter to 2 cm in diameter (a 92% reduction in wound surface area) within 4 weeks of a single laser treatment, and he had near-complete re-epithelialization within 4 weeks of his second laser treatment without blistering or other adverse effects. This novel intervention of using fractionated CO2 for photo-microdebridement could help revolutionize wound care for patients who have RDEB and whose chronic wounds serve as one of their greatest sources of morbidity and mortality. Dissemination to a pediatric audience is critical so that laser protocols might be more thoroughly investigated and incorporated into wound management strategies for this uniquely vulnerable population. PMID:25535263

  11. Laminin-5 mutational analysis in an Italian cohort of patients with junctional epidermolysis bullosa.

    PubMed

    Posteraro, Patrizia; De Luca, Naomi; Meneguzzi, Guerrino; El Hachem, May; Angelo, Corrado; Gobello, Tommaso; Tadini, Gianluca; Zambruno, Giovanna; Castiglia, Daniele

    2004-10-01

    Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by dermal-epidermal separation that is caused by mutations in the genes encoding hemidesmosomal components and laminin-5, the major epithelial adhesion ligand. Here, we report on the mutational analysis of LAMA3, LAMB3, and LAMC2 genes encoding laminin-5 chains in 19 Italian patients, 11 affected with the severe Herlitz (H JEB) and eight with the mild non-Herlitz variant of JEB (non-H JEB). Eighteen mutations, seven of which were novel, were identified and their consequences analyzed at the mRNA and protein level. Premature termination codon mutations in both alleles of LAMB3 or LAMC2 genes were found in nine of the 11 H JEB patients, with a prevalence of mutations in LAMC2. In one case, a homozygous frameshift mutation in LAMB3 was associated to illegitimate splicing leading to non-H JEB. One H JEB patient showed a large intragenic duplication within LAMC2, a genetic defect so far uncovered in laminin-5 genes. Splicing or missense mutations, were prevalent in non-H JEB patients. Collectively, five mutations appeared to be frequent in laminin-5 JEB patients: R635X, 29insC, E210K, W143X in LAMB3 and R95X in LAMC2. These recurrent mutations account for approximately 44% of laminin-5 JEB alleles in Italian patients. PMID:15373767

  12. Somatic correction of junctional epidermolysis bullosa by a highly recombinogenic AAV variant.

    PubMed

    Melo, Sandra P; Lisowski, Leszek; Bashkirova, Elizaveta; Zhen, Hanson H; Chu, Kirk; Keene, Douglas R; Marinkovich, M Peter; Kay, Mark A; Oro, Anthony E

    2014-04-01

    Definitive correction of disease causing mutations in somatic cells by homologous recombination (HR) is an attractive therapeutic approach for the treatment of genetic diseases. However, HR-based somatic gene therapy is limited by the low efficiency of gene targeting in mammalian cells and replicative senescence of primary cells ex vivo, forcing investigators to explore alternative strategies such as retro- and lentiviral gene transfer, or genome editing in induced pluripotent stem cells. Here, we report correction of mutations at the LAMA3 locus in primary keratinocytes derived from a patient affected by recessive inherited Herlitz junctional epidermolysis bullosa (H-JEB) disorder using recombinant adenoassociated virus (rAAV)-mediated HR. We identified a highly recombinogenic AAV serotype, AAV-DJ, that mediates efficient gene targeting in keratinocytes at clinically relevant frequencies with a low rate of random integration. Targeted H-JEB patient cells were selected based on restoration of adhesion phenotype, which eliminated the need for foreign sequences in repaired cells, enhancing the clinical use and safety profile of our approach. Corrected pools of primary cells assembled functional laminin-332 heterotrimer and fully reversed the blistering phenotype both in vitro and in skin grafts. The efficient targeting of the LAMA3 locus by AAV-DJ using phenotypic selection, together with the observed low frequency of off-target events, makes AAV-DJ based somatic cell targeting a promising strategy for ex vivo therapy for this severe and often lethal epithelial disorder. PMID:24390279

  13. 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. PMID:9650620

  14. Inherited junctional epidermolysis bullosa in the German Pointer: establishment of a large animal model.

    PubMed

    Capt, Annabelle; Spirito, Flavia; Guaguere, Eric; Spadafora, Anne; Ortonne, Jean-Paul; Meneguzzi, Guerrino

    2005-03-01

    Junctional epidermolysis bullosa (JEB) is a genodermatosis suitable for gene therapy because conventional treatments are ineffective. Here, we elucidate the genetic basis of mild JEB in a breed of dogs that display all the clinical traits observed in JEB patients. The condition is associated with reduced expression of laminin 5 caused by a homozygous insertion (4818+207ins6.5 kb) of repetitive satellite DNA within intron 35 of the gene (lama3) for the laminin alpha3 chain. The intronic mutation interferes with maturation of the alpha3 pre-messenger RNA resulting in the coexpression of a transcript with a 227 nucleotide insertion and a wild-type mRNA that encodes scant amounts of the alpha3 polypeptide. Our results show that the amino acid sequence and structure of the canine and human alpha3 chain are highly conserved and that the reduced expression of laminin 5 affects the adhesion and clonogenic potential of the JEB keratinocytes. These JEB dogs provide the opportunity to perform gene delivery in a naturally occurring genodermatosis and to evaluate host tolerance to recombinant laminin 5. PMID:15737193

  15. Complete paternal uniparental isodisomy of chromosome 1 resulting in Herlitz junctional epidermolysis bullosa.

    PubMed

    Fassihi, H; Wessagowit, V; Ashton, G H S; Moss, C; Ward, R; Denyer, J; Mellerio, J E; McGrath, J A

    2005-01-01

    Herlitz junctional epidermolysis bullosa (JEB) is an autosomal recessive mechanobullous disorder that results from loss-of-function mutations in the genes encoding the basement membrane component, laminin 5. Typically, there are frameshift, splice site or nonsense mutations on both alleles of either the LAMA3, LAMB3 or LAMC2 genes, with affected individuals inheriting one mutated allele from each parent. In this report, we describe a patient with Herlitz JEB in whom DNA analysis revealed homozygosity for the recurrent nonsense mutation R635X in LAMB3, located on chromosome 1q32.2. However, screening of parental DNA showed that although the patient's father was a heterozygous carrier of this mutation, the mother's DNA showed only wild-type sequence. Subsequent genotype analysis using 13 microsatellite markers spanning chromosome 1 revealed that the affected child was homozygous for the entire series of markers tested and that all of the alleles originated from the father. These results indicate that the Herlitz JEB phenotype in this patient is due to complete paternal isodisomy of chromosome 1 and reduction to homozygosity of the mutant LAMB3 gene locus. This is the fourth case of uniparental disomy to be described in Herlitz JEB, but it represents the first example of complete paternal isodisomy for chromosome 1 with a pathogenic mutation in the LAMB3 gene. These findings have important implications for mutation screening in JEB and for genetic counselling. PMID:15663509

  16. 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

  17. 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

  18. Concha bullosa mucocele with orbital invasion and secondary frontal sinusitis: a case report

    PubMed Central

    2013-01-01

    Background Although concha bullosa (CB) is the most common variants of the middle turbinate, mucocele of CB is uncommon. Furthermore, CB mucocele with orbital invasion and secondary frontal sinusitis has not been reported previously. Case presentation A 42-year-old Korean male presented with gradually progressive proptosis of right eye and right-sided frontal headache. He had previously undergone endoscopic sinus surgery (ESS) 15 and 9 years ago. The endoscopic examination showed an expansive, large middle turbinate with normal mucosa filled the majority of right nasal cavity and displaced the septum to the left. A computed tomography and magnetic resonance imaging showed a well demarcated cystic huge mass at right nasal cavity extending to ethmoid sinus and orbit. The mass caused a bony defect on the lamina papyracea and displaced medial rectus muscle and orbit laterally. Moreover, the right frontal and ethmoid sinus was totally opacified. This article reports orbital invasion and frontal sinusitis complicating a CB mucocele, which was successfully treated by endoscopic resection of the lateral wall of CB and frontal sinusotomy. Conclusions This case illustrates that CB mucocele could develop to such a massive extent that it leads to orbital complication and secondary frontal sinusitis. Therefore, we consider this entity in the differential diagnosis of orbital complications and secondary sinusitis caused by intranasal mass. PMID:24299615

  19. Patient-specific naturally gene-reverted induced pluripotent stem cells in recessive dystrophic epidermolysis bullosa.

    PubMed

    Tolar, Jakub; McGrath, John A; Xia, Lily; Riddle, Megan J; Lees, Chris J; Eide, Cindy; Keene, Douglas R; Liu, Lu; Osborn, Mark J; Lund, Troy C; Blazar, Bruce R; Wagner, John E

    2014-05-01

    Spontaneous reversion of disease-causing mutations has been observed in some genetic disorders. In our clinical observations of severe generalized recessive dystrophic epidermolysis bullosa (RDEB), a currently incurable blistering genodermatosis caused by loss-of-function mutations in COL7A1 that results in a deficit of type VII collagen (C7), we have observed patches of healthy-appearing skin on some individuals. When biopsied, this skin revealed somatic mosaicism resulting in the self-correction of C7 deficiency. We believe this source of cells could represent an opportunity for translational 'natural' gene therapy. We show that revertant RDEB keratinocytes expressing functional C7 can be reprogrammed into induced pluripotent stem cells (iPSCs) and that self-corrected RDEB iPSCs can be induced to differentiate into either epidermal or hematopoietic cell populations. Our results give proof-of-principle that an inexhaustible supply of functional patient-specific revertant cells can be obtained--potentially relevant to local wound therapy and systemic hematopoietic cell transplantation. This technology may also avoid some of the major limitations of other cell therapy strategies, e.g., immune rejection and insertional mutagenesis, which are associated with viral- and nonviral-mediated gene therapy. We believe this approach should be the starting point for autologous cellular therapies using 'natural' gene therapy in RDEB and other diseases. PMID:24317394

  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. PMID:25961909

  1. Identification of novel type VII collagen gene mutations resulting in severe recessive dystrophic epidermolysis bullosa.

    PubMed

    Massé, M; Cserhalmi-Friedman, P B; Falanga, V; Celebi, J T; Martinez-Mir, A; Christiano, A M

    2005-05-01

    In this work, we studied the proband in a small nuclear family of Chinese and Dutch/German descent and identified two novel mutations in the type VII collagen gene leading to recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens variant (HS-RDEB). The maternal mutation is a single base pair deletion of a cytosine nucleotide in exon 26, designated 3472delC, resulting in a frameshift and a premature termination codon (PTC) within the same exon, 7 bp downstream of the site of the mutation. The paternal mutation is a G-->A transition located at the 5' donor splice site within intron 51, designated IVS51 + 1G-->A. This mutation leads to the activation of a cryptic splice site, 32 bp downstream of the mutation site and to subsequent aberrant out-of-frame splicing, resulting in two alternative mRNA transcripts and a downstream PTC. To our knowledge, these two mutations have not been previously reported. These findings extend the body of evidence for compound heterozygous mutations leading to HS-RDEB and provide the basis for prenatal diagnosis in this family. PMID:15807692

  2. 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. PMID:10853786

  3. Epidermolysis bullosa with pyloric atresia: novel mutations in the beta4 integrin gene (ITGB4).

    PubMed Central

    Pulkkinen, L.; Kim, D. U.; Uitto, J.

    1998-01-01

    Epidermolysis bullosa with pyloric atresia (EB-PA; OMIM 226730) is a clinically and genetically heterogeneous autosomal recessive blistering disorder, including lethal and nonlethal variants. Recently, expression of alpha6beta4 integrin, a transmembrane protein of the epithelial basement membranes, has been shown to be altered in these patients. In this work, we have explored the molecular pathology of the lethal form of EB-PA, and we describe novel ITGB4 mutations in five alleles of three patients. The mutation detection strategy included polymerase chain reaction amplification of each exon of ITGB4, followed by heteroduplex analysis and direct nucleotide sequencing. The novel mutations included a homozygous 2-bp deletion in exon 34 (4501delTC), compound heterozygosity for a 2-bp deletion within the paternal allele (120delTG) within exon 3 and a cysteine substitution in the maternal allele (C245G) within exon 7, and the paternal nonsense mutation within exon 4 (Q73X). Thus, three of four distinct mutations predicted truncated polypeptide chains, whereas the missense mutation in the extracellular domain of beta4 integrin may affect ligand binding or dimerization of alpha6 and beta4 integrin subunits. These mutations emphasize the critical importance of the alpha6beta4 integrin in providing stability to the association of epidermis to the underlying dermis at the cutaneous basement membrane zone. Images Figure 1 Figure2 Figure 3 Figure 4 Figure 5 PMID:9422533

  4. Nutritional Outcomes in Children with Epidermolysis Bullosa: The Experiences of Two Centers in Korea

    PubMed Central

    Kim, Kyu-Yeun; Namgung, Ran; Kim, Soo Chan; Eun, Ho Sun; Park, Min Soo; Park, Kook In; Lee, Chul

    2014-01-01

    Purpose Epidermolysis bullosa (EB) is associated with variable risks of extracutaneous manifestations and death. Currently, there is limited information on the clinical course and prognosis of EB in Korea. This study analyzed the nutritional outcomes, clinical morbidity, and mortality of children with EB. Materials and Methods Thirty patients, admitted to Severance Hospital and Gangnam Severance Hospital, from January 2001 to December 2011, were retrospectively enrolled. All patients were diagnosed with EB classified by dermatologists. Results Among the 30 patients, 5 patients were diagnosed with EB simplex, four with junctional EB, and 21 with dystrophic EB. Wound infection occurred in 47% of the patients, and blood culture-proven sepsis was noted in 10% of the patients. Two (9.2%) patients had esophageal stricture and 11 (52.4%) of the dystrophic EB patients received reconstructive surgery due to distal extremity contracture. There were five mortalities caused by sepsis, failure to thrive, and severe metabolic acidosis with dehydration. According to nutrition and growth status, most of the infants (97%) were born as appropriate for gestational age. However, at last follow-up, 56% of the children were below the 3rd percentile in weight, and 50% were below the 3rd percentile in weight for height. Sixty percent of the children had a thrive index below -3. Conclusion Postnatal growth failure is a serious problem in children with EB. Strategies to maximize nutritional support could alleviate growth failure in children with EB, and thus improve clinical outcomes. PMID:24339316

  5. Data on morphological features of mycosis induced by Colletotrichum nymphaeae and Lecanicillium longisporum on citrus orthezia scale.

    PubMed

    Mascarin, Gabriel Moura; Guarín-Molina, Juan Humberto; Arthurs, Steven Paul; Humber, Richard Alan; de Andrade Moral, Rafael; Demétrio, Clarice Garcia Borges; Delalibera, Ítalo

    2016-09-01

    We describe symptoms of mycosis induced by two native fungal entomopathogens of the citrus orthezia scale, Praelongorthezia praelonga (Hemiptera: Ortheziidae), an important pest of citrus orchards. The data presented in this article are related to the article entitled "Seasonal prevalence of the insect pathogenic fungus Colletotrichum nymphaeae in Brazilian citrus groves under different chemical pesticide regimes" [1]. The endemic fungal pathogen, C. nymphaeae, emerges through the thin cuticular intersegmental regions of the citrus orthezia scale body revealing orange salmon-pigmented conidiophores bearing conidial masses, as well as producing rhizoid-like hyphae that extend over the citrus leaf. By contrast, nymphs or adult females of this scale insect infected with Lecanicillium longisporum exhibit profuse outgrowth of bright white-pigmented conidiophores with clusters of conidia emerging from the insect intersegmental membranes, and mycosed cadavers are commonly observed attached to the leaf surface by hyphal extensions. These morphological differences are important features to discriminate these fungal entomopathogens in citrus orthezia scales. PMID:27274531

  6. 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. PMID:25955497

  7. 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

  8. Fixed full-arch implant-supported prostheses in a patient with epidermolysis bullosa: a clinical case history report.

    PubMed

    Agustín-Panadero, Rubén; Gomar-Vercher, Sonia; Peñarrocha-Oltra, David; Guzmán-Letelier, Marcelo; Peñarrocha-Diago, Miguel

    2015-01-01

    Epidermolysis bullosa (EB) is a rare skin disorder characterized by blister formation in response to minor trauma and accompanied by extracutaneous manifestations. The use of endosseous implants to support fixed prostheses for the rehabilitation of patients with recessive dystrophic EB might provide a considerably better clinical treatment outcome than traditional prosthodontic interventions. This case history report describes the clinical management of such an afflicted patient. Implants were placed immediately following teeth extractions and subsequently loaded with fixed full-arch prostheses. This treatment option is proposed for patients with recessive dystrophic EB to preclude mucosal irritation associated with wearing removable prostheses. PMID:25588170

  9. Immunohistochemical analysis of the skin in junctional epidermolysis bullosa using laminin 5 chain specific antibodies is of limited value in predicting the underlying gene mutation.

    PubMed

    McMillan, J R; McGrath, J A; Pulkkinen, L; Kon, A; Burgeson, R E; Ortonne, J P; Meneguzzi, G; Uitto, J; Eady, R A

    1997-06-01

    The anchoring filament protein laminin 5 is composed of three polypeptide chains (alpha 3, beta 3 and gamma 2) each encoded by separate genes (LAMA3, LAMB3 and LAMC2, respectively). Mutations in any of these three genes may give rise to the autosomal recessive blistering skin disease, junctional epidermolysis bullosa. At present, there is no easy way of predicting which of these three genes might harbour the pathogenetic laminin 5 mutations in a case of junctional epidermolysis bullosa. In this study, we assessed whether immunohistochemistry might be helpful in this regard. We performed immunohistochemical labelling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-specific antibodies in 11 patients with junctional epidermolysis bullosa, in whom the laminin 5 mutations had been previously delineated. Although, labelling for the laminin 5 chain bearing the mutations was attenuated or undetectable in all cases, a complete absence of labelling or a reduction in the staining intensity for the other two chains was also seen in all cases. The results showed that immunohistochemical labelling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-specific antibodies is not a specific indicator for which of the laminin 5 chain genes contains the pathogenetic mutations, and is therefore unreliable in screening for individual laminin 5 gene mutations in cases of junctional epidermolysis bullosa. PMID:9217810

  10. 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. PMID:26370913

  11. 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

    2016-01-01

    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

  12. [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. PMID:26645451

  13. Downstream effects of plectin mutations in epidermolysis bullosa simplex with muscular dystrophy.

    PubMed

    Winter, Lilli; Türk, Matthias; Harter, Patrick N; Mittelbronn, Michel; Kornblum, Cornelia; Norwood, Fiona; Jungbluth, Heinz; Thiel, Christian T; Schlötzer-Schrehardt, Ursula; Schröder, Rolf

    2016-01-01

    Mutations of the human plectin gene (PLEC) on chromosome 8q24 cause autosomal recessive epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). In the present study we analyzed the downstream effects of PLEC mutations on plectin protein expression and localization, the structure of the extrasarcomeric desmin cytoskeleton, protein aggregate formation and mitochondrial distribution in skeletal muscle tissue from three EBS-MD patients. PLEC gene analysis in a not previously reported 35-year-old EBS-MD patient with additional disease features of cardiomyopathy and malignant arrhythmias revealed novel compound heterozygous (p.(Phe755del) and p.(Lys1040Argfs*139)) mutations resulting in complete abolition of plectin protein expression. In contrast, the other two patients with different homozygous PLEC mutations showed preserved plectin protein expression with one only expressing rodless plectin variants, and the other markedly reduced protein levels. Analysis of skeletal muscle tissue from all three patients revealed severe disruption of the extrasarcomeric intermediate filament cytoskeleton, protein aggregates positive for desmin, syncoilin, and synemin, degenerative myofibrillar changes, and mitochondrial abnormalities comprising respiratory chain dysfunction and an altered organelle distribution and amount.Our study demonstrates that EBS-MD causing PLEC mutations universally result in a desmin protein aggregate myopathy phenotype despite marked differences in individual plectin protein expression patterns. Since plectin is the key cytolinker protein that regulates the structural and functional organization of desmin filaments, the defective anchorage and spacing of assembled desmin filaments is the key pathogenetic event that triggers the formation of desmin protein aggregates as well as secondary mitochondrial pathology. PMID:27121971

  14. Laminin 5 mutations in junctional epidermolysis bullosa: molecular basis of Herlitz vs. non-Herlitz phenotypes.

    PubMed

    Nakano, Aoi; Chao, Sheau-Chiou; Pulkkinen, Leena; Murrell, Dedee; Bruckner-Tuderman, Leena; Pfendner, Ellen; Uitto, Jouni

    2002-01-01

    Junctional epidermolysis bullosa (JEB) is a group of heritable blistering diseases in which tissue separation occurs within the lamina lucida of the cutaneous basement membrane zone. Clinically, two broad subcategories have been recognized: The Herlitz variant (H-JEB; OMIM 226700) is characterized by early demise of the affected individuals, usually within the first year of life, while non-Herlitz (nH-JEB; OMIM 226650) patients show a milder phenotype with life-long blistering, yet with normal lifespan. In this study, we have examined a cohort of 27 families, 15 with Herlitz and 12 with non-Herlitz JEB, for mutations in the candidate genes, LAMA3, LAMB3, and LAMC2, encoding the subunit polypeptides of laminin 5. The mutation detection strategy consisted of PCR amplification of all exons in these genes, followed by heteroduplex scanning and nucleotide sequencing. We were able to identify pathogenic mutations in both alleles of each proband, the majority of the mutations being in the LAMB3 gene. Examination of the mutation database revealed that most cases with Herlitz JEB harbored premature termination codon (PTC) mutations in both alleles. In non-Herlitz cases, the PTC mutation was frequently associated with a missense mutation or a putative splicing mutation in trans. In three cases with putative splicing mutations, RT-PCR analysis revealed a repertoire of splice variants in-frame, predicting the synthesis of either shortened or lengthened, yet partly functional, polypeptides. These observations would explain the relatively mild phenotype in cases with splicing mutations. Collectively, these findings, together with the global laminin 5 mutation database, contribute to our understanding of the genotype/phenotype correlations explaining the Herlitz vs non-Herlitz phenotypes. PMID:11810295

  15. Targeted inactivation of murine laminin gamma2-chain gene recapitulates human junctional epidermolysis bullosa.

    PubMed

    Meng, Xianmin; Klement, John F; Leperi, Dominic A; Birk, David E; Sasaki, Takako; Timpl, Rupert; Uitto, Jouni; Pulkkinen, Leena

    2003-10-01

    Junctional forms of epidermolysis bullosa (JEB) are associated with mutations in six distinct genes expressed in the cutaneous basement membrane zone; these include LAMA3, LAMB3, and LAMC2, which encode laminin 5 subunit polypeptides, the alpha3-, beta3-, and gamma2-chains, respectively. Here we generated a mouse model for JEB by inactivating the laminin gamma2-chain gene by targeted frameshift deletion of exon 8 in Lamc2. Heterozygous mice were phenotypically normal, whereas the majority of Lamc2-/- mice showed blistering phenotype on days 1 to 2 and died within 5 days of birth. The Lamc2-/- mice demonstrated absent expression of laminin gamma2-chain on the basement membrane zone as well as attenuated expression of alpha3- and beta3-chains of laminin. Transmission electron microscopy revealed rudimentary, poorly developed hemidesmosomes. The epidermis of the Lamc2-/- mice revealed induced apoptosis in the basal cells of the blistered skin, suggesting that cell-matrix adhesion provided by laminin 5 plays a role in cell survival in vivo. Cultured Lamc2-/- keratinocytes demonstrated slightly positive staining with gamma2-chain-specific antibodies, which could be explained by the presence of a transcript with partial restoration of the reading frame owing to alternative splicing in vitro. These cells proliferated in different matrices and attached to type IV collagen and Matrigel as efficiently as the wild-type keratinocytes, whereas their attachment on plastic and laminin was significantly weaker. In summary, Lamc2-/- mouse recapitulates human JEB and provides novel insight into the role of laminin 5 in keratinocyte biology. PMID:14632187

  16. 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

  17. Detection of novel LAMC2 mutations in Herlitz junctional epidermolysis Bullosa.

    PubMed Central

    Pulkkinen, L.; McGrath, J.; Airenne, T.; Haakana, H.; Tryggvason, K.; Kivirikko, S.; Meneguzzi, G.; Ortonne, J. P.; Christiano, A. M.; Uitto, J.

    1997-01-01

    BACKGROUND: Laminin 5, an anchoring filament attachment protein within the lamina lucida of the basement membrane zone involved in the pathogenesis of junctional epidermolysis bullosa (JEB), consists of three polypeptide subunits, the alpha 3, beta 3, and gamma 2 chains which are encoded by the LAMA3, LAMB3, and LAMC2 genes, respectively. To facilitate identification of pathogenetic mutations in LAMC2, a strategy based on direct amplification of genomic DNA by PCR or mRNA by RT-PCR, followed by heteroduplex analysis of the PCR products, was developed. MATERIALS AND METHODS: Primer pairs for amplification of the complete cDNA as well as the 23 individual exons in the genomic DNA, which encode the entire gamma 2 chain of laminin 5, were established. The primers for amplification of exons from genomic DNA were positioned at least 24 bp away from the intron-exon borders in the flanking intronic sequences. For amplification of cDNA generated by RT-PCR, eight primer pairs covering overlapping segments of the entire coding sequence of LAMC2 mRNA were used. The amplified sequences were scanned for pathogenetic mutations and sequence variations in JEB patients and unrelated control individuals by heteroduplex analysis by means of conformation sensitive gel electrophoresis (CSGE). RESULTS: Utilizing the strategy developed in this study, we identified pathogenetic mutations in three patients with the Herlitz (lethal) variant of JEB, and eight intragenic normal polymorphisms, which are useful for linkage analysis, in the LAMC2 gene. CONCLUSIONS: The methodology described in this study is capable of detecting single-base substitutions or small insertions and deletions in the LAMC2 gene. Demonstration of mutations in this gene in JEB patients further emphasizes the role of laminin 5 in providing integrity to the cutaneous basement membrane zone. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 PMID:9085255

  18. Skin microbiota-associated inflammation precedes autoantibody induced tissue damage in experimental epidermolysis bullosa acquisita.

    PubMed

    Ellebrecht, Christoph T; Srinivas, Girish; Bieber, Katja; Banczyk, David; Kalies, Kathrin; Künzel, Sven; Hammers, Christoph M; Baines, John F; Zillikens, Detlef; Ludwig, Ralf J; Westermann, Jürgen

    2016-04-01

    Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune blistering skin disease characterized by autoantibodies against type VII collagen (COL7). Immunization of SJL/J mice with recombinant murine COL7 results in break of tolerance and skin blisters. Strikingly, despite circulating autoantibodies, the same genetic background and identical environmental conditions, 20% of mice remain healthy. To elucidate the regulation of the transition from the presence of autoantibodies to overt autoimmune disease, we characterized the innate and adaptive immune response of mice that remain healthy after immunization and compared it to mice that developed skin disease. Both clinically healthy and diseased SJL/J mice showed circulating autoantibodies and deposition of complement-fixing IgG2c autoantibodies and C3 at the dermal-epidermal junction. However, only in diseased animals significant neutrophil infiltration and increase in FcgRIV expression were observed in the skin. In contrast, the expression of T cell signature cytokines in the T cell zone of the draining lymph node was comparable between clinically healthy and diseased animals after immunization. Surprisingly, health was associated with a decreased expression of CD11c, TNFA and KC (CXCL1) in the skin prior to immunization and could be predicted with a negative predictive value of >80%. Furthermore, mice that did not develop clinical disease showed a significantly higher richness and distinctly clustered diversity of their skin microbiota before immunization. Our data indicate that the decision whether blisters develop in the presence of autoantibodies is governed in the skin rather than in the lymph node, and that a greater richness of cutaneous bacterial species appears to be protective. PMID:26341384

  19. Disseminated mycosis in veiled chameleons (Chamaeleo calyptratus) caused by Chamaeleomyces granulomatis, a new fungus related to Paecilomyces viridis.

    PubMed

    Sigler, Lynne; Gibas, Connie Fe C; Kokotovic, Branko; Bertelsen, Mads F

    2010-09-01

    An outbreak of disseminated granulomatous disease occurred in a group of veiled chameleons (Chamaeleo calyptratus) in a zoo collection. An adult female and six offspring developed large granulomas in multiple organs and were euthanized. At necropsy, roughly spherical yellow-to-white nodules 1 to 3 mm in diameter were grossly visible in the liver and other organs. Histopathology revealed fungal elements that were spherical to ovoid in shape, fragments of slender to irregularly swollen hyphae, and occasional conidia produced on phialides. Fungal isolates were initially suspected on the basis of morphology results to represent Paecilomyces viridis, a species known only from one outbreak of fatal mycosis in carpet chameleons (Furcifer lateralis). Data obtained from morphological studies and from phylogenetic analyses of nuclear ribosomal rRNA (rDNA) sequence data revealed the Danish chameleon isolates to be a related undescribed anamorphic species within the family Clavicipitaceae that includes many insect pathogens. Chamaeleomyces granulomatis gen. et sp. nov. is given as the name for the newly described fungus, and P. viridis is transferred to the new genus as Chamaeleomyces viridis comb. nov. Chamaeleomyces species are distinguished by having basally swollen phialides tapering to a narrow neck, conidia in fragile chains, and pale green to greenish-gray colonies. Both species are dimorphic, producing a transitory yeast stage characterized by ovoid-to-subglobose or subcylindrical yeast-like cells. Chamaeleomyces species appear to be rare but aggressive pathogens of chameleons. PMID:20660211

  20. Disseminated Mycosis in Veiled Chameleons (Chamaeleo calyptratus) Caused by Chamaeleomyces granulomatis, a New Fungus Related to Paecilomyces viridis▿

    PubMed Central

    Sigler, Lynne; Gibas, Connie Fe C.; Kokotovic, Branko; Bertelsen, Mads F.

    2010-01-01

    An outbreak of disseminated granulomatous disease occurred in a group of veiled chameleons (Chamaeleo calyptratus) in a zoo collection. An adult female and six offspring developed large granulomas in multiple organs and were euthanized. At necropsy, roughly spherical yellow-to-white nodules 1 to 3 mm in diameter were grossly visible in the liver and other organs. Histopathology revealed fungal elements that were spherical to ovoid in shape, fragments of slender to irregularly swollen hyphae, and occasional conidia produced on phialides. Fungal isolates were initially suspected on the basis of morphology results to represent Paecilomyces viridis, a species known only from one outbreak of fatal mycosis in carpet chameleons (Furcifer lateralis). Data obtained from morphological studies and from phylogenetic analyses of nuclear ribosomal rRNA (rDNA) sequence data revealed the Danish chameleon isolates to be a related undescribed anamorphic species within the family Clavicipitaceae that includes many insect pathogens. Chamaeleomyces granulomatis gen. et sp. nov. is given as the name for the newly described fungus, and P. viridis is transferred to the new genus as Chamaeleomyces viridis comb. nov. Chamaeleomyces species are distinguished by having basally swollen phialides tapering to a narrow neck, conidia in fragile chains, and pale green to greenish-gray colonies. Both species are dimorphic, producing a transitory yeast stage characterized by ovoid-to-subglobose or subcylindrical yeast-like cells. Chamaeleomyces species appear to be rare but aggressive pathogens of chameleons. PMID:20660211

  1. Genetics Home Reference: Sézary syndrome

    MedlinePlus

    ... of cutaneous T-cell lymphoma after mycosis fungoides , accounting for approximately 3 to 5 percent of cases ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management These resources address the diagnosis or management of ...

  2. A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low (<10%) Mature T Cell Lymphoma (TCL)

    ClinicalTrials.gov

    2016-06-24

    T-cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepato-splenic T-cell Lymphoma; Adult T-cell Leukemia/Lymphoma; Enteropathy Associated T-cell Lymphoma; NK T-cell Lymphoma; Transformed Mycosis Fungoides

  3. 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.

  4. Partial deletion of the LAMA3 gene is responsible for hereditary junctional epidermolysis bullosa in the American Saddlebred Horse.

    PubMed

    Graves, K T; Henney, P J; Ennis, R B

    2009-02-01

    Laminin 5 is a heterotrimeric basement membrane protein integral to the structure and function of the dermal-epidermal junction. It consists of three glycoprotein subunits: the alpha3, beta3 and gamma2 chains, which are encoded by the LAMA3, LAMB3 and LAMC2 genes respectively. A mutation in any of these genes results in the condition known as hereditary junctional epidermolysis bullosa (JEB). A 6589-bp deletion spanning exons 24-27 was found in the LAMA3 gene in American Saddlebred foals born with the skin-blistering condition epitheliogenesis imperfecta. The deletion confirms that this autosomal recessive condition in the American Saddlebred Horse can indeed be classified as JEB and corresponds to Herlitz JEB in humans. A diagnostic test was developed and nine of 175 randomly selected American Saddlebred foals from the 2007 foal crop were found to be carriers of the mutation (frequency of 0.026). PMID:19016681

  5. 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 Central

    Sousa, Márcia Carolline dos Santos; de Paula, Carmen Dea Ribeiro; 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. PMID:26734883

  6. Childhood Epidermolysis Bullosa Acquisita: Confirmation of Diagnosis by Skin Deficient in Type VII Collagen, Enzyme-linked Immunosorbent Assay, and Immunoblotting

    PubMed Central

    Goyal, Nupur; Rao, Raghavendra; Balachandran, C; Pai, Sathish; Bhogal, Balbir S; Schmidt, Enno; Zillikens, Detlef

    2016-01-01

    Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disorder characterized by autoantibodies against Type VII collagen. It usually affects adults; childhood EBA is rare. We describe a 10-year-old girl presenting with recurrent tense blisters predominantly on legs, dorsa of hands and feet accompanied by oral erosions since the age of 5 years. Direct immunofluorescence (IF) microscopy showed linear deposition of IgG and C3 along the basement membrane zone (BMZ); indirect IF microscopy on salt-split skin revealed staining of IgG to the dermal side of the split. The patient's serum did not show BMZ staining in recessive dystrophic epidermolysis bullosa skin deficient for Type VII collagen, thus confirming autoantibody reactivity against Type VII collagen. Circulating antibodies against the immunodominant noncollagenous 1 domain of Type VII collagen were detected by ELISA and immunoblotting studies. The patient was treated with oral corticosteroids and dapsone with good improvement. PMID:27293257

  7. Childhood Epidermolysis Bullosa Acquisita: Confirmation of Diagnosis by Skin Deficient in Type VII Collagen, Enzyme-linked Immunosorbent Assay, and Immunoblotting.

    PubMed

    Goyal, Nupur; Rao, Raghavendra; Balachandran, C; Pai, Sathish; Bhogal, Balbir S; Schmidt, Enno; Zillikens, Detlef

    2016-01-01

    Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disorder characterized by autoantibodies against Type VII collagen. It usually affects adults; childhood EBA is rare. We describe a 10-year-old girl presenting with recurrent tense blisters predominantly on legs, dorsa of hands and feet accompanied by oral erosions since the age of 5 years. Direct immunofluorescence (IF) microscopy showed linear deposition of IgG and C3 along the basement membrane zone (BMZ); indirect IF microscopy on salt-split skin revealed staining of IgG to the dermal side of the split. The patient's serum did not show BMZ staining in recessive dystrophic epidermolysis bullosa skin deficient for Type VII collagen, thus confirming autoantibody reactivity against Type VII collagen. Circulating antibodies against the immunodominant noncollagenous 1 domain of Type VII collagen were detected by ELISA and immunoblotting studies. The patient was treated with oral corticosteroids and dapsone with good improvement. PMID:27293257

  8. Extensive acantholysis as the major histological feature of a severe case of Dowling Meara-epidermolysis bullosa simplex: a reappraisal of acantholysis in the newborn.

    PubMed

    Darwich, Esteve; Vicente, Asunción; Bolling, Maria C; González-Enseñat, Maria A; Cusi, Victoria; Fortuny, Claudia; Bombí, José A; Jonkman, Marcel F; Mascaró, José M

    2011-01-01

    Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders characterized by blistering and skin fragility secondary to mechanical trauma. Epidermolysis bullosa simplex (EBS) is the most frequent form of EB, with Dowling-Meara (DM-EBS) subtype being the most severe form in this group. Conventional histopathological evaluation is usually of low value in the diagnosis of EB, and significant histological features have rarely been reported in this group of diseases. We describe a case of severe DM-EBS in which acantholysis was observed in the histological examination. This finding led us to consider other diagnoses, such as neonatal pemphigus vulgaris or lethal acantholytic EB. Histological, immunological, ultrastructural and genetic tests were performed, leading to a final diagnosis of DM-EBS. Therefore, we believe that DM-EBS should be considered in the differential diagnosis of a newborn with blisters, where acantholysis is the main histological feature. PMID:21856558

  9. Compound heterozygosity for a dominant glycine substitution and a recessive internal duplication mutation in the type XVII collagen gene results in junctional epidermolysis bullosa and abnormal dentition.

    PubMed

    McGrath, J A; Gatalica, B; Li, K; Dunnill, M G; McMillan, J R; Christiano, A M; Eady, R A; Uitto, J

    1996-06-01

    Junctional epidermolysis bullosa is a heterogeneous autosomal recessively inherited blistering skin disorder associated with fragility at the dermal-epidermal junction. Previously, mutations in this condition have been described in the three genes for the anchoring filament protein laminin 5 (LAMA3, LAMB3, and LAMC2), in the gene encoding the hemidesmosome-associated beta4 integrin (ITGB4), and in the gene for the hemidesmosomal protein type XVII collagen (COL17A1/BPAG2). In this study, we report a patient with a form of junctional epidermolysis bullosa with skin fragility and dental anomalies who is a compound heterozygote for a novel combination of mutations, ie, a glycine substitution mutation in one allele and an internal duplication in the other allele of COL17A1. The patient also has two offspring, both of whom have inherited the glycine substitution mutation, whereas the other COL17A1 allele is normal. The latter individuals show no evidence of skin fragility but have marked dental abnormalities with enamel hypoplasia and pitting. The clinical phenotype of junctional epidermolysis bullosa in the proband in this family probably arises due to a combination of the glycine substitution and the internal duplication in COL17A1, whereas the dental abnormalities of her offspring may be the result of the glycine substitution in COL17A1 alone, resulting in this dominantly inherited clinical phenotype. PMID:8669466

  10. Subcutaneous Mycosis Due to Cladosporium cladosporioides and Bipolaris cynodontis from Assam, North-East India and Review of Published Literature.

    PubMed

    Nath, Reema; Barua, Shyamanta; Barman, Jahnabi; Swargiary, Pallabi; Borgohain, Mondita; Saikia, Lahari

    2015-12-01

    A large number of phaeoid fungi cause infection in humans and other animals which is characterized by the basic development of sclerotic body, dark-coloured filamentous hyphae as well as yeast-like cells in the invaded tissue. Two cases of subcutaneous mycosis in immunocompetent male patients aged 55 and 58 years attending Dermatology outpatient department of a tertiary care hospital in Assam, north-east India, are reported. The first case was diagnosed as chromoblastomycosis which was caused by Cladosporium cladosporioides. The patient clinically presented with a chronic verrucous and nodular growth of 32-year duration on the left foot and leg. Identification of the species was done by sequencing the D1/D2 region of LSU (large subunit 28S rDNA). The patient was treated with surgical resection and oral itraconazole which showed good clinical response and total regression of lesion after 9 months. The second case due to Bipolaris cynodontis presented as verrucous exophytic growth over the dorsum of the right foot of 1-year duration which was diagnosed as chromoblastomycosis. The identification of the species was done by sequencing the ITS region. The patient was started with oral itraconazole but was lost to follow-up. Chromoblastomycosis due to Cladosporium cladosporioides is rare. Bipolaris cynodontis is not yet reported as a cause of human infection. The aetiological role of this fungus was confirmed by repeated isolation of the fungus from the lesion and direct microscopy. Molecular identification methods can increase the spectrum of black moulds causing human infection in coming years. We are reporting these two cases with review of the available literature. PMID:26198088

  11. Clinical Significance and Molecular Characterization of Nonsporulating Molds Isolated from the Respiratory Tracts of Bronchopulmonary Mycosis Patients with Special Reference to Basidiomycetes

    PubMed Central

    Singh, Pradeep Kumar; Kathuria, Shallu; Agarwal, Kshitij; Gaur, Shailendra Nath; Meis, Jacques F.

    2013-01-01

    Nonsporulating molds (NSMs), especially basidiomycetes, have predominantly been reported as human pathogens responsible for allergic and invasive disease. Their conventional identification is problematic, as many isolates remain sterile in culture. Thus, inconclusive culture reports might adversely affect treatment decisions. The clinical significance of NSMs in pulmonary mycoses is poorly understood. We sequenced the internal transcribed spacer (ITS) region and D1/D2 domain of the larger subunit (LSU) of 52 NSMs isolated from respiratory specimens. The basidiomycetes were the predominant NSMs, of which Schizophyllum commune was the most common agent in allergic bronchopulmonary mycosis (ABPM), followed by Ceriporia lacerata in invasive fungal disease. Porostereum spadiceum, Phanaerochaete stereoides, Neosartorya fischeri, and Marasmiellus palmivorus were the other molds observed. Application of ITS and LSU region sequencing identified 92% of the isolates. The antifungal susceptibility data revealed that all basidiomycetes tested were susceptible to amphotericin B and resistant to caspofungin, fluconazole, and flucytosine. Except for 3 isolates of S. commune and a solitary isolate of M. palmivorus, all basidiomycetes had low MICs for itraconazole, posaconazole, and voriconazole. Basidiomycetes were isolated from patients with ABPM, invasive pulmonary mycosis/pneumonia, or fungal balls. In addition, the majority of the basidiomycetes were isolated from patients with chronic respiratory disorders who were sensitized to one of the basidiomycetous fungi and demonstrated precipitating antibodies against the incriminating fungi, indicating an indolent tissue reaction. Thus, isolation of basidiomycetes from the lower respiratory tract could be significant, and it is important to monitor these patients in order to prevent subsequent lung damage. PMID:23903552

  12. Isolation and Characterization of a Novel Single-Stranded RNA Virus Infectious to a Marine Fungoid Protist, Schizochytrium sp. (Thraustochytriaceae, Labyrinthulea)

    PubMed Central

    Takao, Yoshitake; Nagasaki, Keizo; Mise, Kazuyuki; Okuno, Tetsuro; Honda, Daiske

    2005-01-01

    Thraustochytrids are cosmopolitan osmoheterotrophic microorganisms that play important roles as decomposers, producers of polyunsaturated fatty acids, and pathogens of mollusks, especially in coastal ecosystems. SssRNAV, a novel single-stranded RNA (ssRNA) virus infecting the marine fungoid protist Schizochytrium sp. (Labyrinthulea, Thraustochytriaceae) was isolated from the coastal water of Kobe Harbor, Japan, in July 2000, and its basic characteristics were examined. The virus particle is icosahedral, lacks a tail, and is ca. 25 nm in diameter. SssRNAV formed crystalline arrays and random assemblies within the cytoplasm of host cells, and it was also concentrated along the intracellular membrane structures. By means of one-step growth experiments, the lytic cycle and the burst size were estimated to be <8 h and 5.8 × 103 to 6.4 × 104 infectious units per host cell, respectively. SssRNAV had a single molecule of ssRNA that was approximately 10.2 kb long, three major proteins (37, 34, and 32 kDa), and two minor proteins (80 and 18 kDa). Although SssRNAV was considered to have some similarities with invertebrate viruses belonging to the family Dicistroviridae based on its partial nucleotide sequence, further genomic analysis is required to determine the detailed classification and nomenclature of SssRNAV. Our results indicate that viral infection is one of the significant factors controlling the dynamics of thraustochytrids and provide new insights into understanding the ecology of these organisms. PMID:16085844

  13. Aminoglycosides Restore Full-length Type VII Collagen by Overcoming Premature Termination Codons: Therapeutic Implications for Dystrophic Epidermolysis Bullosa

    PubMed Central

    Cogan, Jon; Weinstein, Jacqueline; Wang, Xinyi; Hou, Yingping; Martin, Sabrina; South, Andrew P; Woodley, David T; Chen, Mei

    2014-01-01

    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. PMID:25155989

  14. 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.

  15. 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.

  16. [Dental alterations in junctional epidermolysis bullosa--report of a patient with a mutation in the LAMB3-gene].

    PubMed

    Sadler, Elke; Laimer, Martin; Diem, Anja; Klausegger, Alfred; Pohla-Gubo, Gabriele; Muss, Wolfgang; Hachleitner, Johannes; Stadlhuber, Rudolf; Bauer, Johann W; Hintner, Helmut

    2005-05-01

    During early odontogenesis the basement membrane is known to be important in epithelio-mesenchymal interactions. Mutations in the gene of one of the major structural proteins of the basement membrane such as laminin 5 might therefore be expected either to seriously compromise ameloblast differentiation and/ or interfere with normal basement-membrane formation and degradation and thus the binding of the ameloblasts to their underlying matrix. Teeth of patients suffering from junctional epidermolysis bullosa (JEB) can be severely affected by abnormal dental development and generalized or focal enamel hypoplasia. Those changes are found in 100% of individuals with JEB but the expression is variable. Beside the quantitative alterations, changes in the prismatic structure and orientation of enamel crystals are described. In addition JEB is associated with an increased risk for dental caries, caused by developmentally compromised enamel and external factors such as difficulties in maintaining oral hygiene because of oral lesions or a softer and more refined high caloric diet. Dental care includes three main strategies: Prevention by consequent oral hygiene and reduction of cariogenic nutrition is of paramount importance to minimize caries development; the restoration of enamel and dentin defects with fillings and stainless steel crowns to guarantee structure and function of teeth; and extractions of most severely affected teeth with osteolytic foci to remove continuous sources of oral infections. PMID:16372803

  17. 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.

  18. A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy

    PubMed Central

    Fritsch, Anja; Loeckermann, Stefan; Kern, Johannes S.; Braun, Attila; Bösl, Michael R.; Bley, Thorsten A.; Schumann, Hauke; von Elverfeldt, Dominik; Paul, Dominik; Erlacher, Miriam; Berens von Rautenfeld, Dirk; Hausser, Ingrid; Fässler, Reinhard; Bruckner-Tuderman, Leena

    2008-01-01

    Dystrophic epidermolysis bullosa (DEB) is a severe skin fragility disorder associated with trauma-induced blistering, progressive soft tissue scarring, and increased risk of skin cancer. DEB is caused by mutations in type VII collagen. In this study, we describe the generation of a collagen VII hypomorphic mouse that serves as an immunocompetent animal model for DEB. These mice expressed collagen VII at about 10% of normal levels, and their phenotype closely resembled characteristics of severe human DEB, including mucocutaneous blistering, nail dystrophy, and mitten deformities of the extremities. The oral blistering experienced by these mice resulted in growth retardation, and repeated blistering led to excessive induction of tissue repair, causing TGF-β1–mediated contractile fibrosis generated by myofibroblasts and pseudosyndactyly in the extremities. Intradermal injection of WT fibroblasts resulted in neodeposition of collagen VII and functional restoration of the dermal-epidermal junction. Treated areas were also resistant to induced frictional stress. In contrast, untreated areas of the same mouse showed dermal-epidermal separation following induced stress. These data demonstrate that fibroblast-based treatment can be used to treat DEB in a mouse model and suggest that this approach may be effective in the development of clinical therapeutic regimens for patients with DEB. PMID:18382769

  19. 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. PMID:26802230

  20. A missense mutation (G1506E) in the adhesion G domain of laminin-5 causes mild junctional epidermolysis bullosa.

    PubMed

    Scaturro, Maria; Posteraro, Patrizia; Mastrogiacomo, Alessandro; Zaccaria, Maria Letizia; De Luca, Naomi; Mazzanti, Cinzia; Zambruno, Giovanna; Castiglia, Daniele

    2003-09-12

    Laminin-5 is the major adhesion ligand for epithelial cells. Mutations in the genes encoding laminin-5 cause junctional epidermolysis bullosa (JEB), a recessive inherited disease characterized by extensive epithelial-mesenchymal disadhesion. We describe a JEB patient compound heterozygote for two novel mutations in the gene (LAMA3) encoding the laminin alpha3 chain. The maternal mutation (1644delG) generates mRNA transcripts that undergo nonsense-mediated decay. The paternal mutation results in the Gly1506-->Glu substitution (G1506E) within the C-terminal globular region of the alpha3 chain (G domain). Mutation G1506E affects the proper folding of the fourth module of the G domain and results in the retention of most of the mutated polypeptide within the endoplasmic reticulum (ER). However, scant amounts of the mutated laminin-5 are secreted, undergo physiologic extracellular maturation, and correctly localize within the cutaneous basement membrane zone in patient's skin. Our findings represent the first demonstration of an ER-retained mutant laminin-5 leading to a mild JEB phenotype. PMID:12943669

  1. A frameshift mutation within LAMC2 is responsible for Herlitz type junctional epidermolysis bullosa (HJEB) in black headed mutton sheep.

    PubMed

    Mömke, Stefanie; Kerkmann, Andrea; Wöhlke, Anne; Ostmeier, Miriam; Hewicker-Trautwein, Marion; Ganter, Martin; Kijas, James; Distl, Ottmar

    2011-01-01

    Junctional epidermolysis bullosa (JEB) is a hereditary mechanobullous skin disease in humans and animals. A Herlitz type JEB was identified in German Black Headed Mutton (BHM) sheep and affected lambs were reproduced in a breeding trial. Affected lambs showed skin and mucous membranes blistering and all affected lambs died within the first weeks of life. The pedigree data were consistent with a monogenic autosomal recessive inheritance. Immunofluorescence showed a reduced expression of laminin 5 protein which consists of 3 subunits encoded by the genes LAMA3, LAMB3 and LAMC2. We screened these genes for polymorphisms. Linkage and genome-wide association analyses identified LAMC2 as the most likely candidate for HJEB. A two base pair deletion within exon 18 of the LAMC2 gene (FM872310:c.2746delCA) causes a frameshift mutation resulting in a premature stop codon (p.A928*) 13 triplets downstream of this mutation and in addition, introduces an alternative splicing of exon 18 LAMC2. This deletion showed a perfect co-segregation with HJEB in all 740 analysed BHM sheep. Identification of the LAMC2 deletion means an animal model for HJEB is now available to develop therapeutic approaches of relevance to the human form of this disease. PMID:21573221

  2. Cloning of the beta 3 chain gene (LAMB3) of human laminin 5, a candidate gene in junctional epidermolysis bullosa.

    PubMed

    Pulkkinen, L; Gerecke, D R; Christiano, A M; Wagman, D W; Burgeson, R E; 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 bp 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. PMID:7774918

  3. 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. PMID:27143720

  4. [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. PMID:27349061

  5. 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. PMID:26380979

  6. High Local Concentrations of Intradermal MSCs Restore Skin Integrity and Facilitate Wound Healing in Dystrophic Epidermolysis Bullosa.

    PubMed

    Kühl, Tobias; Mezger, Markus; Hausser, Ingrid; Handgretinger, Rupert; Bruckner-Tuderman, Leena; Nyström, Alexander

    2015-08-01

    Dystrophic epidermolysis bullosa (DEB) is an incurable skin fragility disorder caused by mutations in the COL7A1 gene, coding for the anchoring fibril protein collagen VII (C7). Life-long mechanosensitivity of skin and mucosal surfaces is associated with large body surface erosions, chronic wounds, and secondary fibrosis that severely impede functionality. Here, we present the first systematic long-term evaluation of the therapeutic potential of a mesenchymal stromal cell (MSC)-based therapy for DEB. Intradermal administration of MSCs in a DEB mouse model resulted in production and deposition of C7 at the dermal-epidermal junction, the physiological site of function. The effect was dose-dependent with MSCs being up to 10-fold more potent than dermal fibroblasts. MSCs promoted regeneration of DEB wounds via normalization of dermal and epidermal healing and improved skin integrity through de novo formation of functional immature anchoring fibrils. Additional benefits were gained by MSCs' anti-inflammatory effects, which led to decreased immune cell infiltration into injured DEB skin. In our setting, the clinical benefit of MSC injections lasted for more than 3 months. We conclude that MSCs are viable options for localized DEB therapy. Importantly, however, the cell number needed to achieve therapeutic efficacy excludes the use of systemic administration. PMID:25858020

  7. A Sporadic Neonatal Case of Epidermolysis Bullosa Simplex Generalized Intermediate with KRT5 and KRT14 Gene Mutations

    PubMed Central

    Wakiguchi, Hiroyuki; Hasegawa, Shunji; Maeba, Shinji; Kimura, Sasagu; Ito, Satoko; Tateishi, Hiroshi; Ueda, Kazuhiro; Ohga, Shouichi

    2016-01-01

    Background Epidermolysis bullosa simplex (EBS) is a rare genodermatosis resulting from multiple gene mutations, including KRT5 and KRT14. The clinical expression of the mechanobullous skin fragility disease has not been fully explained by the genotype. Case Description An 11-day-old Japanese newborn infant was hospitalized because of herpetiform skin blistering on the feet, which expanded systemically after birth. There was no evidence of virus infection. The biopsied skin lesion showed a blister on the lamina densa without keratin clumps, indicating a diagnosis of EBS-generalized intermediate. We punctured the blisters to remove the contents daily, which led to no exacerbation or infection. The genetic study determined that the patient carried double substitutions of KRT5 c.1424A > G (p.E475G) and KRT14 c.1237G > A (p.A413T). The asymptomatic mother and sister carried the KRT14 substitution, but the healthy father had no substitution of the KRT gene. Conclusion This is the first report of EBS-generalized intermediate in a newborn with de novo KRT5 gene mutation and KRT14 gene polymorphism, and no familial history of epidermolysis. Neonatal blistering due to EBS requires optimal skin management after excluding infectious and immunobullous diseases. PMID:26929861

  8. A two-step multidisciplinary approach to treat recurrent esophageal strictures in children with epidermolysis bullosa dystrophica.

    PubMed

    Vowinkel, Thorsten; Laukoetter, Mike; Mennigen, Rudolf; Hahnenkamp, Klaus; Gottschalk, Antje; Boschin, Matthias; Frosch, Michael; Senninger, Norbert; Tübergen, Dirk

    2015-06-01

    In children with severe generalized recessive dystrophic epidermolysis bullosa (RDEB), esophageal scarring leads to esophageal strictures with dysphagia, followed by malnutrition and delayed development. We describe a two-step multidisciplinary therapeutic approach to overcome malnutrition and growth retardation. In Step 1, under general anesthesia, orthograde balloon dilation of the esophagus is followed by gastrostomy creation using a direct puncture technique. In Step 2, further esophageal strictures are treated by retrograde dilation via the established gastrostomy; this step requires only a short sedation period. A total of 12 patients (median age 7.8 years, range 6 weeks to 17 years) underwent successful orthograde balloon dilation of esophageal strictures combined with direct puncture gastrostomy. After 12 and 24 months in 11 children, a substantial improvement of growth and nutrition was achieved (body mass index [BMI] standard deviation score [SDS] + 0.59 and + 0.61, respectively). In one child, gastrostomy was removed because of skin ulcerations after 10 days. Recurrent esophageal strictures were treated successfully in five children. The combined approach of balloon dilation and gastrostomy is technically safe in children with RDEB, and helps to promote catch-up growth and body weight. In addition, recurrent esophageal strictures can be treated successfully without general anesthesia in a retrograde manner via the established gastrostomy. PMID:25590175

  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

    2016-03-01

    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. PMID:26439431

  10. Lysyl Hydroxylase 3 Localizes to Epidermal Basement Membrane and Is Reduced in Patients with Recessive Dystrophic Epidermolysis Bullosa

    PubMed Central

    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. PMID:26380979

  11. 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

  12. Mechanisms of Fibroblast Cell Therapy for Dystrophic Epidermolysis Bullosa: High Stability of Collagen VII Favors Long-term Skin Integrity

    PubMed Central

    Kern, Johannes S; Loeckermann, Stefan; Fritsch, Anja; Hausser, Ingrid; Roth, Wera; Magin, Thomas M; Mack, Claudia; Müller, Marcel L; Paul, Oliver; Ruther, Patrick; Bruckner-Tuderman, Leena

    2009-01-01

    Here, we report on the first systematic long-term study of fibroblast therapy in a mouse model for recessive dystrophic epidermolysis bullosa (RDEB), a severe skin-blistering disorder caused by loss-of-function of collagen VII. Intradermal injection of wild-type (WT) fibroblasts in >50 mice increased the collagen VII content at the dermal–epidermal junction 3.5- to 4.7-fold. Although the active biosynthesis lasted <28 days, collagen VII remained stable and dramatically improved skin integrity and resistance to mechanical forces for at least 100 days, as measured with a digital 3D-skin sensor for shear forces. Experiments using species-specific antibodies, collagen VII–deficient fibroblasts, gene expression analyses, and cytokine arrays demonstrated that the injected fibroblasts are the major source of newly deposited collagen VII. Apart from transitory mild inflammation, no adverse effects were observed. The cells remained within an area ≤10 mm of the injection site, and did not proliferate, form tumors, or cause fibrosis. Instead, they became gradually apoptotic within 28 days. These data on partial restoration of collagen VII in the skin demonstrate the excellent ratio of clinical effects to biological parameters, support suitability of fibroblast-based therapy approaches for RDEB, and, as a preclinical test, pave way to human clinical trials. PMID:19568221

  13. 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. PMID:26183725

  14. High Local Concentrations of Intradermal MSCs Restore Skin Integrity and Facilitate Wound Healing in Dystrophic Epidermolysis Bullosa

    PubMed Central

    Kühl, Tobias; Mezger, Markus; Hausser, Ingrid; Handgretinger, Rupert; Bruckner-Tuderman, Leena; Nyström, Alexander

    2015-01-01

    Dystrophic epidermolysis bullosa (DEB) is an incurable skin fragility disorder caused by mutations in the COL7A1 gene, coding for the anchoring fibril protein collagen VII (C7). Life-long mechanosensitivity of skin and mucosal surfaces is associated with large body surface erosions, chronic wounds, and secondary fibrosis that severely impede functionality. Here, we present the first systematic long-term evaluation of the therapeutic potential of a mesenchymal stromal cell (MSC)-based therapy for DEB. Intradermal administration of MSCs in a DEB mouse model resulted in production and deposition of C7 at the dermal-epidermal junction, the physiological site of function. The effect was dose-dependent with MSCs being up to 10-fold more potent than dermal fibroblasts. MSCs promoted regeneration of DEB wounds via normalization of dermal and epidermal healing and improved skin integrity through de novo formation of functional immature anchoring fibrils. Additional benefits were gained by MSCs' anti-inflammatory effects, which led to decreased immune cell infiltration into injured DEB skin. In our setting, the clinical benefit of MSC injections lasted for more than 3 months. We conclude that MSCs are viable options for localized DEB therapy. Importantly, however, the cell number needed to achieve therapeutic efficacy excludes the use of systemic administration. PMID:25858020

  15. 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. PMID:26739954

  16. A Sporadic Neonatal Case of Epidermolysis Bullosa Simplex Generalized Intermediate with KRT5 and KRT14 Gene Mutations.

    PubMed

    Wakiguchi, Hiroyuki; Hasegawa, Shunji; Maeba, Shinji; Kimura, Sasagu; Ito, Satoko; Tateishi, Hiroshi; Ueda, Kazuhiro; Ohga, Shouichi

    2016-03-01

    Background Epidermolysis bullosa simplex (EBS) is a rare genodermatosis resulting from multiple gene mutations, including KRT5 and KRT14. The clinical expression of the mechanobullous skin fragility disease has not been fully explained by the genotype. Case Description An 11-day-old Japanese newborn infant was hospitalized because of herpetiform skin blistering on the feet, which expanded systemically after birth. There was no evidence of virus infection. The biopsied skin lesion showed a blister on the lamina densa without keratin clumps, indicating a diagnosis of EBS-generalized intermediate. We punctured the blisters to remove the contents daily, which led to no exacerbation or infection. The genetic study determined that the patient carried double substitutions of KRT5 c.1424A > G (p.E475G) and KRT14 c.1237G > A (p.A413T). The asymptomatic mother and sister carried the KRT14 substitution, but the healthy father had no substitution of the KRT gene. Conclusion This is the first report of EBS-generalized intermediate in a newborn with de novo KRT5 gene mutation and KRT14 gene polymorphism, and no familial history of epidermolysis. Neonatal blistering due to EBS requires optimal skin management after excluding infectious and immunobullous diseases. PMID:26929861

  17. Delivery of Amphotericin B for Effective Treatment of Candida Albicans Induced Dermal Mycosis in Rats via Emulgel System: Formulation and Evaluation

    PubMed Central

    Ganeshpurkar, Aditya; Vaishya, Pooja; Jain, Sumeet; Pandey, Vikas; Bansal, Divya; Dubey, Nazneen

    2014-01-01

    Background: Amphotericin B (AmB) is among the gold standard antifungal agents used for the treatment of the wide range of fungal infections. However, the drug has various side- effects. Transdermal approach for the delivery of drug is one of the accepted and convenient modes of drug delivery. Aim: The current work was designed to formulate and to evaluate the AmB emulgel system. Materials and Methods: In the preparation of AmB emulgel, Carbopol 930 was used as a gel in this study. The formulation was evaluated for viscosity, spreadability, drug content, drug release and in vitro and in vivo antifungal testing. Results: AmB emulgel was found to penetrate skin effectively and without any irritation. Further, in vivo studies revealed effective therapeutic potential against Candida albicans induced dermal mycosis. Conclusions: The current work, for the first time, revealed effective delivery of AmB across the skin. PMID:25071257

  18. Isolation and characterization of a novel single-stranded RNA Virus infectious to a marine fungoid protist, Schizochytrium sp. (Thraustochytriaceae, Labyrinthulea).

    PubMed

    Takao, Yoshitake; Nagasaki, Keizo; Mise, Kazuyuki; Okuno, Tetsuro; Honda, Daiske

    2005-08-01

    Thraustochytrids are cosmopolitan osmoheterotrophic microorganisms that play important roles as decomposers, producers of polyunsaturated fatty acids, and pathogens of mollusks, especially in coastal ecosystems. SssRNAV, a novel single-stranded RNA (ssRNA) virus infecting the marine fungoid protist Schizochytrium sp. (Labyrinthulea, Thraustochytriaceae) was isolated from the coastal water of Kobe Harbor, Japan, in July 2000, and its basic characteristics were examined. The virus particle is icosahedral, lacks a tail, and is ca. 25 nm in diameter. SssRNAV formed crystalline arrays and random assemblies within the cytoplasm of host cells, and it was also concentrated along the intracellular membrane structures. By means of one-step growth experiments, the lytic cycle and the burst size were estimated to be <8 h and 5.8 x 10(3) to 6.4 x 10(4) infectious units per host cell, respectively. SssRNAV had a single molecule of ssRNA that was approximately 10.2 kb long, three major proteins (37, 34, and 32 kDa), and two minor proteins (80 and 18 kDa). Although SssRNAV was considered to have some similarities with invertebrate viruses belonging to the family Dicistroviridae based on its partial nucleotide sequence, further genomic analysis is required to determine the detailed classification and nomenclature of SssRNAV. Our results indicate that viral infection is one of the significant factors controlling the dynamics of thraustochytrids and provide new insights into understanding the ecology of these organisms. PMID:16085844

  19. Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa.

    PubMed

    McGrath, J A; Gatalica, B; Christiano, A M; Li, K; Owaribe, K; McMillan, J R; Eady, R A; Uitto, J

    1995-09-01

    Junctional epidermolysis bullosa (JEB) is a heterogeneous autosomal recessively inherited blistering skin disorder associated with fragility at the dermal-epidermal junction. Characteristic ultrastructural findings in JEB are abnormalities in the hemidesmosome-anchoring filament complexes. These focal attachment structures, which extend from the intracellular compartment of the basal keratinocytes to the underlying basement membrane, have been shown to be hypoplastic or rudimentary in different forms of JEB. Previously, in different JEB phenotypes, mutations have been found in the three genes for the anchoring filament component laminin 5 (LAMA3, LAMB3, and LAMC2) and in the gene for the hemidesmosome-associated integrin beta 4 subunit. Here, we describe the first mutations in the gene encoding the 180-kD bullous pemphigoid antigen (BPAG2), a transmembranous hemidesmosomal collagen, also known as type XVII collagen (COL17A1). The patient is affected with generalized atrophic benign epidermolysis bullosa (GABEB), a rare variant of JEB, and is a compound heterozygote for premature termination codons on both alleles. These novel findings emphasize the molecular heterogeneity of this group of genodermatoses, and attest to the importance of BPAG2 in maintaining adhesion between the epidermis and the dermis. PMID:7550320

  20. Immunogenicity of decidual stromal cells in an epidermolysis bullosa patient and in allogeneic hematopoietic stem cell transplantation patients.

    PubMed

    Kaipe, Helen; Carlson, Lena-Maria; Erkers, Tom; Nava, Silvia; Molldén, Pia; Gustafsson, Britt; Qian, Hua; Li, Xiaoguang; Hashimoto, Takashi; Sadeghi, Behnam; Alheim, Mats; Ringdén, Olle

    2015-06-15

    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

  1. 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.

  2. A Cross Sectional, Observational Survey to Assess Levels and Predictors of Psychological Wellbeing in Adults with Epidermolysis Bullosa

    PubMed Central

    Dures, Emma; Rumsey, Nichola; Morris, Marianne; Gleeson, Kate

    2013-01-01

    Epidermolysis bullosa (EB) describes a cluster of genetically determined skin disorders. Symptoms can be painful, disabling and disfiguring, yet there is little research on the psychological impact of the disease. The study aim was to measure psychological wellbeing in adults with EB; and to examine the association between psychological wellbeing and self efficacy, health locus of control and adjustment to appearance in an observational, cross sectional survey. Questionnaire packs comprising the General Health Questionnaire (GHQ-12), the General Self Efficacy Scale (GSE), the Multidimensional Health Locus of Control Scale (MHLOC), and the Derriford Appearance Scale (DAS-24), were sent to approximately 385 adults with EB. The data were analysed using SPSS. Eighty-seven participants responded. Scores on the GHQ-12 showed non-problematic psychological health in 36% of the sample; levels bordering on clinical disorder in 32.1% and severe psychological distress in 31.9%. No correlations were found between demographic factors (age and sex) or clinical factors (EB type and perceived severity) and psychological well-being. Scores on the GSE, the internal locus of control sub-scale of the MHLOC and the DAS-24 showed them to be statistically significant correlates of psychological wellbeing (P<0.001; P<0.018; and P<0.001 respectively). In a regression analysis, adjustment to appearance and self efficacy accounted for 24% of the variation in psychological wellbeing. Adults with EB might be at risk of experiencing poor psychological health. Interventions designed to enhance disease self management, self efficacy and improve body image are likely to be beneficial in this clinical group. PMID:26973893

  3. Novel mutations in the LAMC2 gene in non-Herlitz junctional epidermolysis bullosa: effects on laminin-5 assembly, secretion, and deposition.

    PubMed

    Castiglia, D; Posteraro, P; Spirito, F; Pinola, M; Angelo, C; Puddu, P; Meneguzzi, G; Zambruno, G

    2001-09-01

    Laminin-5 is the major adhesion ligand of epithelial cells. Mutations in the three genes (LAMA3, LAMB3, LAMC2) encoding the laminin-5 chains cause junctional epidermolysis bullosa, a clinically and genetically heterogeneous blistering skin disease. Here, we describe a non-Herlitz junctional epidermolysis bullosa patient, compound heterozygote for two novel mutations affecting the LAMC2 gene. The mutation in the paternal allele is a de novo splice site mutation (522-1G-->A) that results in in-frame skipping of exon 4 and synthesis of a mutated gamma2 polypeptide (gamma2Delta4) carrying a 33 amino acid deletion within the N-terminal domain V. The maternal mutation is a one base pair insertion (3511insA) in the 3' terminal exon of LAMC2 resulting in a frameshift and a premature termination codon. Mutation 3511insA is predicted to lead to the synthesis of a gamma2 polypeptide (gamma2t) disrupted in its alpha-helical C-terminal structure and truncated of the last 25 amino acids. Keratinocytes isolated from the patient's skin showed a markedly decreased level of gamma2 chain mRNA and secreted scant amounts of laminin-5, which undergoes physiologic proteolytic processing. To investigate the biologic function of the laminin-5 molecules synthesized by the patient, mutant gamma2 cDNAs were transiently expressed in gamma2-null keratinocytes. Transfection of the gamma2Delta4 cDNA resulted in restoration of laminin-5 deposition onto the culture substrate, which demonstrates that the gamma2 polypeptides carrying a deletion in domain V, upstream of the gamma2 proteolytic cleavage site, are assembled into native laminin-5 that is secreted and extracellularly processed. In contrast, transfection of a mutant cDNA expressing the gamma2t chain failed to restore laminin-5 immunoreactivity, which indicates that integrity of the gamma2 C-terminal amino acid sequences is required for laminin-5 assembly. These results correlate for the first time a functional alteration in a laminin-5

  4. Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

    ClinicalTrials.gov

    2014-09-02

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mantle Cell 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 Mantle Cell Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Waldenström Macroglobulinemia

  5. Application of the procedural consolidation concept to surgical treatment of children with epidermolysis bullosa: a retrospective analysis

    PubMed Central

    Karaman Ilić, Maja; Kern, Josipa; Babić, Irena; Šimić, Diana; Kljenak, Antun; Majerić Kogler, Višnja

    2011-01-01

    Aim To assess the efficacy of the procedural consolidation concept (PCC) at reducing the number of sessions of general anesthesia necessary for treating children with epidermolysis bullosa (EB). Methods We examined the records of children treated at Children's Hospital of Zagreb between April 1999 and December 2007. Children treated before the introduction of PCC in January 2005 (n = 39) and after (n = 48) were analyzed in order to determine the effect of PCC on the occurrence of complications, days of hospitalization, and number of hospitalizations. Results During the study period, 53 patients underwent 220 sessions of general anesthesia for a total of 743 surgical interventions per session. Before the introduction of PCC (n = 39 patients, 83 sessions), the median number of interventions per session was 2 (range 1-5), and after the introduction of PCC (n = 48 patients, 137 sessions) it was 4 (range 3-7, P < 0.001). After the introduction of PCC, the median number of complications per anesthesia session increased from 2 (range 0-10) to 3 (range 0-10) (P = 0.027), but the median number of complications per surgical procedure decreased from 1 (range 0-10) to 0.6 (range 0-2.5) (P < 0.001). PCC lengthened each anesthesia session from a median of 65 minutes (range 35-655) to 95 minutes (range 50-405), (P < 0.001). Total length of hospitalization was similar before (median 1, range 1-4) and after (median 1, range 1-3) introduction of PCC (P = 0.169). The number of hospitalization days per procedure was 3 times lower after the introduction of PCC (median 0.3, range 0.2-3) than before (median 1, range 0.75-1.7) (P < 0.001). Conclusion PCC should be considered an option in the surgical treatment of children with EB. PMID:21853547

  6. Ligation of the ipsilateral common carotid artery and topical treatment for the prevention of epistaxis from guttural pouch mycosis in horses.

    PubMed

    Cousty, M; Tricaud, C; De Beauregard, T; Picandet, V; Bizon-Mercier, C; Tessier, C

    2016-01-01

    The objective of the study was to evaluate the effect of ligation of the ipsilateral common carotid artery (CCA) combined with various antimycotic treatments for the prevention of epistaxis in horses with guttural pouch mycosis. For each case, ipsilateral ligation of the CCA was performed, followed by application of various topical medications under endoscopic guidance. Frequency and number of treatments, outcome and recurrence of haemorrhage were retrospectively recorded. Twenty-four horses were included. Topical medication was administered by detachment of the diphtheric membrane and spraying (n=16) or by intralesional injection directly in the plaques using a transendoscopic needle (n=8). Epistaxis recurred in five horses (20.8 per cent), causing death of four horses (16.6 per cent). The mean number of treatments was 6.3±4.0 (range 2-14) for all topical treatments. Ligation of the ipsilateral CCA and topical medication carries a fair prognosis for avoidance of recurrent episodes of epistaxis, but fatal haemorrhage can occur. Removal of the fungal plaque and topical treatment of the underlying lesion appeared to speed up resolution of the mycotic mucosal lesions. The described technique is a salvage procedure when financial or technical constraints prevent the use of transarterial catheter occlusion techniques. PMID:26657942

  7. Role of Granulocyte Macrophage Colony-Stimulating Factor in Host Defense Against Pulmonary Cryptococcus neoformans Infection during Murine Allergic Bronchopulmonary Mycosis

    PubMed Central

    Chen, Gwo-Hsiao; Olszewski, Michal A.; McDonald, Roderick A.; Wells, Jason C.; Paine, Robert; Huffnagle, Gary B.; Toews, Galen B.

    2007-01-01

    We investigated the role of granulocyte macrophage colony-stimulating factor (GM-CSF) in host defense in a murine model of pulmonary cryptococcosis induced by intratracheal inoculation of Cryptococcus neoformans. Pulmonary C. neoformans infection of C57BL/6 mice is an established model of an allergic bronchopulmonary mycosis. Our objective was to determine whether GM-CSF regulates the pulmonary Th2 immune response in C. neoformans-infected C57BL/6 mice. Long-term pulmonary fungistasis was lost in GM-CSF knockout (GM−/−) mice, resulting in increased pulmonary burden of fungi between weeks 3 and 5. GM-CSF was required for the early influx of macrophages and CD4 and CD8 T cells into the lungs but was not required later in the infection. Lack of GM-CSF also resulted in reduced eosinophil recruitment and delayed recruitment of mononuclear cells into the airspace. Macrophages from GM+/+ mice showed numerous hallmarks of alternatively activated macrophages: higher numbers of intracellular cryptococci, YM1 crystals, and induction of CCL17. These hallmarks are absent in macrophages from GM−/− mice. Mucus-producing goblet cells were abundantly present within the bronchial epithelial layer in GM+/+ mice but not in GM−/− mice at week 5 after infection. Production of both Th1 and Th2 cytokines was impaired in the absence of GM-CSF, consistent with both reduced C. neoformans clearance and absence of allergic lung pathology. PMID:17322386

  8. Novel compound heterozygous mutation in LAMC2 genes (c.79G>A and 382insT) in Herlitz junctional epidermolysis bullosa.

    PubMed

    Jeon, In Kyung; Kim, Song-Ee; Kim, Soo-Chan

    2014-04-01

    Junctional epidermolysis bullosa (JEB) is a heritable blistering skin disease characterized by separation within the lamina lucida. It is caused by mutations in the LAMA3, LAMB3 and LAMC2 genes encoding the α3-, β3- and γ2-chains, respectively, of laminin-332. JEB Herlitz type (JEB-H) is a lethal blistering disease with severe cutaneous and extracutaneous involvements caused by null mutations in the gene encoding laminin-332. Here, we report a proband with JEB-H who is a compound heterozygote for two novel mutations in LAMC2; a missense mutation (c.79G>A) and an insertion mutation (382insT) leading to a premature termination codon. PMID:24533970

  9. A recurrent homozygous nonsense mutation within the LAMA3 gene as a cause of Herlitz junctional epidermolysis bullosa in patients of Pakistani ancestry: evidence for a founder effect.

    PubMed

    McGrath, J A; Kivirikko, S; Ciatti, S; Moss, C; Christiano, A M; Uitto, J

    1996-04-01

    The anchoring filament protein laminin 5 is abnormally expressed in the skin of patients with Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a H-JEB child of first-cousin Pakistani parents, and identified a homozygous C-to-T transition in the LAMA3 gene of laminin 5 resulting in a premature termination codon (CGA-TGA) on both alleles. This mutation, R650X, has been previously reported in two other seemingly unrelated H-JEB individuals of Pakistani ancestry. Although this mutation may represent a mutational hotspot within the LAMA3 gene, haplotype analysis based on a silent intragenic polymorphism (GCC/GCG, alanine 429; GenBank no. L34155), and on three flanking microsatellite polymorphism (D18S45, D18S478, and D18S480), suggests that a common ancestral allele may be present in all three cases. PMID:8618022

  10. A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in Herlitz junctional epidermolysis bullosa: prenatal exclusion in a fetus at risk.

    PubMed

    McGrath, J A; Kivirikko, S; Ciatti, S; Moss, C; Dunnill, G S; Eady, R A; Rodeck, C H; Christiano, A M; Uitto, J

    1995-09-01

    Mutations in the three genes (LAMA3, LAMB3, and LAMC2) that encode the three chains (alpha 3, beta 3, and gamma 2, respectively) of laminin 5, a protein involved in epidermal-dermal adhesion, have been established as the genetic basis for the inherited blistering skin disorder, Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a child with H-JEB and identified a nonsense mutation in the alpha 3 chain gene (LAMA3) consisting of a homozygous C-to-T transition resulting in a premature termination codon (CGA-->TGA) on both alleles. The parents were shown to be heterozygous carriers of the same mutation. Direct mutation analysis was used to perform DNA-based prenatal diagnosis from a chorionic villus biopsy at 10 weeks' gestation in a subsequent pregnancy. The fetus was predicted to be genotypically normal with respect to the LAMA3 mutation. PMID:8530087

  11. Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis bullosa

    PubMed Central

    Karuthedath Vellarikkal, Shamsudheen; Jayarajan, Rijith; Verma, Ankit; Nair, Sreelata; Ravi, Rowmika; Senthivel, Vigneshwar; Sivasubbu, Sridhar; Scaria, Vinod

    2016-01-01

    Dystrophic epidermolysis bullosa simplex (DEB) is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB can be inherited in a recessive or dominant form and the recessive form of DEB (RDEB) is more severe. In the present study, we identify a novel p.G2254fs mutation in COL7A1 gene causing a sporadic case of RDEB by whole exome sequencing (WES). Apart from adding a novel frameshift Collagen VII mutation to the repertoire of known mutations reported in the disease, to the best of our knowledge, this is the first report of a genetically characterized case of DEB from India. PMID:27408687

  12. Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa

    SciTech Connect

    Gatalica, B.; Pulkkinen, L.; Li, K.

    1997-02-01

    Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal variant of junctional epidermolysis bullosa (JEB). Previous findings have suggested that type XVII collagen is the candidate gene for mutations in this disease. We now have cloned the entire human type XVII collagen gene (COL17A1) and have elucidated its intron-exon organization. The gene comprises 56 distinct exons, which span {approximately}52 kb of the genome, on the long arm of chromosome 10. It encodes a polypeptide, the {alpha}1(XVII) chain, consisting of an intracellular globular domain, a transmembrane segment, and an extracellular domain that contains 15 separate collagenous subdomains, the largest consisting of 242 amino acids. We also have developed a strategy to identify mutations in COL17A1 by use of PCR amplification of genomic DNA, using primers placed on the flanking introns. The PCR products are scanned for sequence variants by heteroduplex analysis using conformation-sensitive gel electrophoresis and then are subjected to direct automated sequencing. We have identified several intragenic polymorphisms in COL17A1, as well as mutations, in both alleles, in two Finnish families with GABEB. The probands in both families showed negative immunofluorescence staining with an anti-type XVII collagen antibody. In one family, the proband was homozygous for a 5-bp deletion, 2944del5, which resulted in frameshift and a premature termination codon of translation. The proband in the other family was a compound heterozygote, with one allele containing the 2944del5 mutation and the other containing a nonsense mutation, Q1023X. These results expand the mutation database in different variants of JEB, and they attest to the functional importance of type XVII collagen as a transmembrane component of the hemidesmosomes at the dermal/epidermal junction. 48 refs., 9 figs., 3 tabs.

  13. Characterization of mutations of the type VII collagen gene (COL7A1) in recessive dystrophic epidermolysis bullosa mitis (M-RDEB) from three Korean patients.

    PubMed

    Ryoo, Y W; Kim, B C; Lee, K S

    2001-06-01

    In recent years, the molecular basis for the main subtypes of epidermolysis bullosa (EB) has been elucidated with pathogenetic mutations delineated in ten different genes encoding structural components of the dermal-epidermal junction. Both the autosomal dominant and recessive forms of dystrophic EB (DEB) is caused by mutations in the COL7A1 gene. Type VII collagen is a major component of anchoring fibrils, structural elements that stabilize the attachment of the basement membrane to underlying dermis. Recent delineation of the exon-intron organization of the COL7A1 gene provided the basis for the comprehensive design of PCR primer pairs that amplified exons in genomic DNA by placing the primers on the flanking introns. A number of COL7A1 mutations have been reported and some genotype-phenotype correlations are starting to emerge. In this study, we examined mutational analyses from three Korean patients with recessive dystrophic EB (RDEB) mitis. We designed and optimized primers according to the previously reported sequences. Such PCR amplification products can be examined by electrophoretic scanning technique, CSGE heteroduplex analyses. Utilizing heteroduplex analyses, we have identified a number of sequence variants in COL7A1 both in unaffected individuals and in patients with M-RDEB. Mutation detection of the COL7A1 gene revealed six allelic mutations (V6677E, P6685S, Y3749S, P6084S, P6695R and G6697C). We suggest that the full length of type VII collagen polypeptide are synthesized, but those missense mutations, that may affect a critical amino acid, can alter the conformation of the protein and interferes with the assembly and packing of type VII collagen molecules into anchoring fibrils. Immunohistochemical study of skin biopsies by use of anti-type VII collagen antibody showed markedly reduced staining and presence of a dermo/epidermal cleavage. This is the first report of a COL7A1 mutation study in DEB from Korean patients. We hope that these data

  14. Leucoderma associated with flares of erythrodermic cutaneous T-cell lymphomas: four cases. The French Study Group of Cutaneous Lymphomas.

    PubMed

    Bouloc, A; Grange, F; Delfau-Larue, M H; Dieng, M T; Tortel, M C; Avril, M F; Revuz, J; Bagot, M; Wechsler, J

    2000-10-01

    We describe four patients with erythrodermic cutaneous T-cell lymphomas (two with erythrodermic mycosis fungoides, and two with Sézary syndrome) who presented with extensive hypopigmented lesions that occurred during flares of their cutaneous disease. These cases must be distinguished from previously described hypopigmented mycosis fungoides where hypopigmented lesions were the sole manifestation of the lymphoma. In two cases a biopsy was performed on hypopigmented skin, showing an infiltrate of atypical lymphocytes with epidermotropism and absence of melanocytes, as in vitiligo. It is suggested that the hypopigmentation could be due to the cytotoxicity of tumour or reactional lymphocytes directed against melanocytes. PMID:11069466

  15. SIN Retroviral Vectors Expressing COL7A1 Under Human Promoters for Ex Vivo Gene Therapy of Recessive Dystrophic Epidermolysis Bullosa

    PubMed Central

    Titeux, Matthias; Pendaries, Valérie; Zanta-Boussif, Maria A; Décha, Audrey; Pironon, Nathalie; Tonasso, Laure; Mejia, José E; Brice, Agnes; Danos, Olivier; Hovnanian, Alain

    2010-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is caused by loss-of-function mutations in COL7A1 encoding type VII collagen which forms key structures (anchoring fibrils) for dermal–epidermal adherence. Patients suffer since birth from skin blistering, and develop severe local and systemic complications resulting in poor prognosis. We lack a specific treatment for RDEB, but ex vivo gene transfer to epidermal stem cells shows a therapeutic potential. To minimize the risk of oncogenic events, we have developed new minimal self-inactivating (SIN) retroviral vectors in which the COL7A1 complementary DNA (cDNA) is under the control of the human elongation factor 1α (EF1α) or COL7A1 promoters. We show efficient ex vivo genetic correction of primary RDEB keratinocytes and fibroblasts without antibiotic selection, and use either of these genetically corrected cells to generate human skin equivalents (SEs) which were grafted onto immunodeficient mice. We achieved long-term expression of recombinant type VII collagen with restored dermal–epidermal adherence and anchoring fibril formation, demonstrating in vivo functional correction. In few cases, rearranged proviruses were detected, which were probably generated during the retrotranscription process. Despite this observation which should be taken under consideration for clinical application, this preclinical study paves the way for a therapy based on grafting the most severely affected skin areas of patients with fully autologous SEs genetically corrected using a SIN COL7A1 retroviral vector. PMID:20485266

  16. A homozygous nonsense mutation in the {alpha}3 chain gene of laminin 5 (LAMA3) in Herlitz junctional epidermolysis bullosa: Prenatal exclusion in a fetus at risk

    SciTech Connect

    McGrath, J.A.; Ciatti, S.; Christiano, A.M.

    1995-09-01

    Mutations in the three genes (LAMA3, LAMB3, and LAMC2) that encode the three chains ({alpha}3, {Beta}3, and {gamma}2, respectively) of laminin 5, a protein involved in epidermal-dermal adhesion, have been established as the genetic basis for the inherited blistering skin disorder, Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a child with H-JEB and identified a nonsense mutation in the {alpha}3 chain gene (LAMA3) consisting of a homozygous C-to-T transition resulting in a premature termination codon (CGA {r_arrow} TGA) on both alleles. The parents were shown to be heterozygous carriers of the same mutation. Direct mutation analysis was used to perform DNA-based prenatal diagnosis from a chorionic villus biopsy at 10 weeks` gestation in a subsequent pregnancy. The fetus was predicted to be genotypically normal with respect to the LAMA3 mutation. 15 refs., 1 fig.

  17. Glycine substitutions in the triple-helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance

    SciTech Connect

    Christiano, A.M.; McGrath, J.A.; Uitto, J.; Kong Chong Tan

    1996-04-01

    The dystrophic forms of epidermolysis bullosa (DEB) are characterized by fragility of the skin and mucous membranes. DEB can be inherited in either an autosomal dominant or autosomal recessive pattern, and the spectrum of clinical severity is highly variable. The unifying diagnostic hallmark of DEB is abnormalities in the anchoring fibrils, which consist of type VII collagen, and recently, mutations in the corresponding gene, COL7A1, have been disclosed in a number of families. In this study, we report six families with glycine substitution mutations in the triple-helical region of type VII collagen. Among the six families, two demonstrated a mild phenotype, and the inheritance of the mutation was consistent with the dominantly inherited form of DEB. In the four other families, the mutation was silent in the heterozygous state but, when present in the homozygous state, or combined with a second mutation, resulted in a recessively inherited DEB phenotype. Type VII collagen is, therefore, unique among the collagen genes, in that different glycine substitutions can be either silent in heterozygous individuals or result in a dominantly inherited DEB. Inspection of the locations of the glycine substitutions along the COL7A1 polypeptide suggests that the consequences of these mutations, in terms of phenotype and pattern of inheritance, are position independent. 29 refs., 4 figs., 2 tabs.

  18. A Male Patient with Humoral Hypercalcemia of Malignancy (HHM) with Leukocytosis Caused by Cutaneous Squamous Cell Carcinoma Resulting from Recessive Dystrophic Epidermolysis Bullosa

    PubMed Central

    Miura, Kohji; Umegaki, Noriko; Kitaoka, Taichi; Kubota, Takuo; Namba, Noriyuki; Etani, Yuri; Hirai, Haruhiko; Kogaki, Shigetoyo; Nakajima, Shigeo; Takahashi, Yuji; Tamai, Katsuto; Katayama, Ichiro; Ozono, Keiichi

    2011-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin disorder. Although the patients are at risk for cutaneous squamous cell carcinoma (SCC), no case of cutaneous SCC derived from RDEB with humoral hypercalcemia of malignancy (HHM) has been reported. We present the first case report of a male patient with HHM with leukocytosis caused by cutaneous SCC resulting from RDEB. A 20-yr-old Japanese male patient with RDEB; the diagnosis was confirmed by electron microscopic examination, suffered an intractable skin ulcer and hypercalcemia and leukocytosis. PTH-rP, SCC antigen and Granulocyte colony-stimulating factor (G-CSF) levels were elevated. The histological diagnosis of the skin lesion was made well-differentiated SCC. Immunohistochemical staining showed the expression of PTH-rP in atypical tumor cells. For the control of hypercalcemia before an amputation, we used zoledronate safely and could control the serum Ca concentration in the normal range. After the amputation of his right leg including SCC, leukocytosis improved immediately and PTH-rP in blood decreased to the normal range. One month after the amputation, local recurrence of cutaneous SCC and multiple lung metastases were observed. PTH-rP increased gradually associated with hypercalcemia. Although the patient reached an unfortunate turning point about 4 mo after the amputation, we propose that zoledronate is an effective and safe treatment for HHM with cardiorenal complications. PMID:23926398

  19. Genetic linkage of type VII collagen (COL7A1) to dominant dystrophic epidermolysis bullosa in families with abnormal anchoring fibrils.

    PubMed Central

    Ryynänen, M; Ryynänen, J; Sollberg, S; Iozzo, R V; Knowlton, R G; Uitto, J

    1992-01-01

    Epidermolysis bullosa (EB) in a group of genodermatoses characterized by the fragility of skin. Previous studies on the dystrophic (scarring) forms of EB have suggested abnormalities in anchoring fibrils, morphologically recognizable attachment structures that provide stability to the association of the cutaneous basement membrane to the underlying dermis. Since type VII collagen is the major component of the anchoring fibrils, we examined the genetic linkage of dominant dystrophic EB (EBDD) and the type VII collagen gene (COL7A1) locus, which we have recently mapped to chromosome 3p, in three large kindreds with abnormal anchoring fibrils. Strong genetic linkage of EBDD and COL7A1 loci was demonstrated with the maximum logarithm of odds (LOD) score of 8.77 at theta = 0. This linkage was further confirmed with two additional markers in this region of the short arm of chromosome 3, and these analyses allowed further refinement of the map locus of COL7A1. Since there were no recombinants between the COL7A1 and EBDD loci, our findings suggest that type VII collagen is the candidate gene that may harbor the mutations responsible for the EB phenotype in these three families. Images PMID:1347297

  20. Cloning of the laminin {alpha}3 chain gene (LAMA3) and identification of a homozygous deletion in a patient with Herlitz junctional epidermolysis bullosa

    SciTech Connect

    Vidal, F.; Ortonne, J.P. |; Galliano, M.F.

    1995-11-20

    Laminin 5 and laminin 6 are basement membrane proteins synthesized by the basal cells of stratifying squamous epithelia. Altered expression of laminin 5 has been associated with Herlitz junctional epidermolysis bullosa (H-JEB), a severe epidermal blistering disorder inherited as an autosomal recessive disease. We have isolated cDNA clones encoding the {alpha}3 chain of laminin 5 and searched for mutations in the LAMA3 gene in H-JEB patients. In one H-JEB family, an affected individual exhibited drastically reduced immunoreactivity to antibodies directed against the {alpha}3 chain of laminin 5 and an impaired expression of the corresponding mRNA transcripts. RT-PCR analysis of mRNA extracted from the proband`s keratinocytes identified a homozygous single basepair deletion in the transcripts encoding the laminin {alpha}3A and {alpha}3B isoforms. The mutation causes a frameshift and premature termination codon in both alleles of the LAMA3 gene. Inheritance of the clinical H-JEB phenotype was consistent with the segregation of the mutated allele in the family. We also report the identity of the {alpha} chains of laminin 5 and epiligrin and provide evidence that LAMA3 transcripts are distinct from the laminin 6 {alpha} chain mRNA. 35 refs., 5 figs., 1 tab.

  1. A recurrent laminin 5 mutation in British patients with lethal (Herlitz) junctional epidermolysis bullosa: evidence for a mutational hotspot rather than propagation of an ancestral allele.

    PubMed

    Ashton, G H; Mellerio, J E; Dunnill, M G; Pulkkinen, L; Christiano, A M; Uitto, J; Eady, R A; McGrath, J A

    1997-05-01

    The three genes (LAMA3, LAB3 and LAMC2) that encode the anchoring filament protein, laminin 5, may all harbour pathogenetic mutations in the autosomal recessive blistering skin disorder, junctional epidermolysis bullosa (JEB). Recently, one particular mutation, R635X in the LAMB3 gene, has been found to account for approximately 40% of all JEB laminin 5 mutations (Kivirikko et al., Hum Mol Genet 1996; 5: 231-7). In this study, we assessed the frequency of this mutation in 12 British patients with lethal (Herlitz) JEB using PCR amplification of genomic DNA and restriction endonuclease digestion. The mutation R635X was fond in seven of 24 (29%) mutant alleles, confirming its relative frequency within the British gene pool. In addition, haplotype analysis using intragenic polymorphisms showed that the mutation arose on at least four different haplotype backgrounds, suggesting it represents a mutational hotspot rather than propagation of a common British ancestral allele. These findings support the hypermutable nature of this CpG dinucleotide and have implications in screening for laminin 5 gene mutations in British and other patients with JEB. PMID:9205497

  2. Maternal uniparental disomy of chromosome 1 with reduction to homozygosity of the LAMB3 locus in a patient with Herlitz junctional epidermolysis bullosa.

    PubMed

    Pulkkinen, L; Bullrich, F; Czarnecki, P; Weiss, L; Uitto, J

    1997-09-01

    Junctional epidermolysis bullosa (JEB) is an autosomal recessive disorder characterized by blister formation at the level of the lamina lucida within the cutaneous basement-membrane zone. Classic lethal JEB (Herlitz type [H-JEB]; OMIM 226700) is frequently associated with premature-termination-codon mutations in both alleles of one of the three genes (LAMA3, LAMC2, or LAMB3) encoding the subunit polypeptides (alpha3, beta3, and gamma2) of laminin 5. In this study, we describe a unique patient with H-JEB, who was homozygous for a nonsense mutation, Q243X, in the LAMB3 gene on chromosome 1 and who had normal karyotype 46,XY. The mother was found to be a carrier of the Q243X mutation, whereas the father had two normal LAMB3 alleles. Nonpaternity was excluded by use of 11 microsatellite markers from six different chromosomes. The use of 17 partly or fully informative microsatellite markers spanning the entire chromosome 1 revealed that the patient had both maternal uniparental meroisodisomy of a 35-cM region on 1q containing the maternal LAMB3 mutation and maternal uniparental heterodisomy of other regions of chromosome 1. Thus, the results suggested that reduction to homozygosity of the 1q region containing the maternal LAMB3 mutation caused the H-JEB phenotype. The patient was normally developed at term and did not show overt dysmorphisms or malformations. This is the first description of uniparental disomy of human chromosome 1. PMID:9326326

  3. Laminin 5 genes and Herlitz junctional epidermolysis bullosa: novel mutations and polymorphisms in the LAMB3 and LAMC2 genes. Mutations in brief no. 190. Online.

    PubMed

    Kon, A; Pulkkinen, L; Hara, M; Tamai, K; Tagami, H; Hashimoto, I; Uitto, J

    1998-01-01

    Herlitz junctional epidermolysis bullosa (H-JEB; OMIM #226700) is a lethal, autosomal recessive blistering disorder characterized by fragility of the skin and other specialized epithelia. Previously, mutations in the laminin 5 genes (LAMA3, LAMB3, and LAMC2) have been disclosed, most of them in LAMB3. In this study, we have examined the genetic basis of H-JEB in three families utilizing heteroduplex analysis and automated nucleotide sequencing. In one family, the proband was compound heterozygote for previously unpublished LAMB3 mutations, 1482delC and W95X. In two other families, the probands were found to be homozygous for novel nonsense mutations C553X and K822X in the LAMC2 gene. These mutations result in premature termination codons and predict truncation of the corresponding polypeptides. Also, during the search of laminin 5 mutations, 18 LAMB3 and LAMC2 polymorphisms were discovered, 9 of them being previously undescribed. Delineation of novel homozygous nonsense mutations in the LAMB3 and LAMC2 genes, with previous demonstrations of LAMA3 mutations, re-emphasizes the concept that stop codon mutations in both alleles of any of the three laminin 5 genes result in the severe H-JEB phenotype. PMID:10660342

  4. Cloning of the laminin alpha 3 chain gene (LAMA3) and identification of a homozygous deletion in a patient with Herlitz junctional epidermolysis bullosa.

    PubMed

    Vidal, F; Baudoin, C; Miquel, C; Galliano, M F; Christiano, A M; Uitto, J; Ortonne, J P; Meneguzzi, G

    1995-11-20

    Laminin 5 and laminin 6 are basement membrane proteins synthesized by the basal cells of stratifying squamous epithelia. Altered expression of laminin 5 has been associated with Herlitz junctional epidermolysis bullosa (H-JEB), a severe epidermal blistering disorder inherited as an autosomal recessive disease. We have isolated cDNA clones encoding the alpha 3 chain of laminin 5 and searched for mutations in the LAMA3 gene in H-JEB patients. In one H-JEB family, an affected individual exhibited drastically reduced immunoreactivity to antibodies directed against the alpha 3 chain of laminin 5 and an impaired expression of the corresponding mRNA transcripts. RT-PCR analysis of mRNA extracted from the proband's keratinocytes identified a homozygous single basepair deletion in the transcripts encoding the laminin alpha 3A and alpha 3B isoforms. The mutation causes a frameshift and premature termination codon in both alleles of the LAMA3 gene. Inheritance of the clinical H-JEB phenotype was consistent with the segregation of the mutated allele in the family. We also report the identity of the alpha chains of laminin 5 and epiligrin and provide evidence that LAMA3 transcripts are distinct from the laminin 6 alpha chain mRNA. PMID:8586427

  5. A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in lethal (Herlitz) junctional epidermolysis bullosa.

    PubMed

    Kivirikko, S; McGrath, J A; Baudoin, C; Aberdam, D; Ciatti, S; Dunnill, M G; McMillan, J R; Eady, R A; Ortonne, J P; Meneguzzi, G

    1995-05-01

    The inherited mechanobullous disorder, junctional epidermolysis bullosa (JEB), is characterized by extensive blistering and erosions of the skin and mucous membranes. The diagnostic hallmarks of JEB include ultrastructural abnormalities in the hemidesmosomes of the cutaneous basement membrane zone, as well as an absence of staining with antibodies against the anchoring filament protein, laminin 5. Therefore, the three genes encoding alpha 3, beta 3 and gamma 2 chains of laminin 5, known as LAMA3, LAMB3 and LAMC2, are candidate genes for JEB. We have previously demonstrated mutations in the LAMB3 and LAMC2 genes in several families with JEB. We initiated mutation analysis from an affected child by PCR amplification of individual LAMA3 exons, followed by heteroduplex analysis. Nucleotide sequencing of heteroduplexes identified a homozygous nonsense mutation within domain I/II of the alpha 3 chain. These findings provide the first evidence that nonsense mutations within the LAMA3 gene are also involved in the pathogenesis of JEB, and indicate that mutations of all three genes of laminin 5 can result in the JEB phenotype. PMID:7633458

  6. Health-related quality of life in epidermolysis bullosa: Validation of the Dutch QOLEB questionnaire and assessment in the Dutch population.

    PubMed

    Yuen, Wing Yan; Frew, John W; Veerman, Kelly; van den Heuvel, Edwin R; Murrell, Dedee F; Jonkman, Marcel F

    2014-07-01

    Defining the health-related quality of life (HRQoL) in patients suffering from the heritable blistering disease epidermolysis bullosa (EB) is important in assessing the efficacy of new treatments. The quality of life in EB questionnaire (QOLEB) is an English 17-item EB-specific HRQoL measurement tool. The aim of this study was to develop a validated and reliable QOLEB in Dutch and assess the HRQoL in Dutch EB patients. The QOLEB was translated to Dutch according to protocol. Fifty-five adult patients across 4 EB subtypes participated. The QOLEB had excellant correlation with the Skindex-29 (ρs = 0.86), good correlation with the SF-36 physical score (ρs = -0.75), and moderate correlation with the SF-36 mental score (ρs = -0.43). The discriminative validity between the 4 different EB subtypes was significant (p = 0.002). The internal consistency was excellent (α = 0.905), and the test-retest reliability strong (ρs = 0.88). In conclusion, the Dutch QOLEB is a reliable and valid instrument for the assessment of the HRQoL in adult EB patients. PMID:24337132

  7. Rescue of the mucocutaneous manifestations by human cord blood derived nonhematopoietic stem cells in a mouse model of recessive dystrophic epidermolysis bullosa.

    PubMed

    Liao, Yanling; Ivanova, Larisa; Zhu, Hongwen; Yahr, Ashlin; Ayello, Janet; van de Ven, Carmella; Rashad, Ahmed; Uitto, Jouni; Christiano, Angela M; Cairo, Mitchell S

    2015-06-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin blistering disease caused by mutations in COL7A1-encoding type VII collagen (C7). Currently, there is no curative therapy for patients with RDEB. Our previous studies demonstrated that human umbilical cord blood (HUCB) derived unrestricted somatic stem cells (USSCs) express C7 and facilitate wound healing in a murine wounding model. The primary objective of this study is to investigate the therapeutic functions of USSCs in the C7 null (Col7a1(-/-) ) C57BL6/J mice, a murine model of RDEB. We demonstrated that intrahepatic administration of USSCs significantly improved the blistering phenotype and enhanced the life span in the recipients. The injected USSCs trafficked to the sites of blistering and were incorporated in short-term in the recipients' skin and gastrointestinal tract. Consistent with an overall histological improvement in the epidermal-dermal adherence following USSC treatment, the expression of C7 at the basement membrane zone was detected and the previously disorganized integrin α6 distribution was normalized. We also demonstrated that USSCs treatment induced an infiltration of macrophages with a regenerative "M2" phenotype. Our data suggest that HUCB-derived USSCs improved the RDEB phenotype through multiple mechanisms. This study has warranted future clinical investigation of USSCs as a novel and universal allogeneic stem cell donor source in selected patients with RDEB. PMID:25640200

  8. Intravenously Administered Recombinant Human Type VII Collagen Derived from Chinese Hamster Ovary Cells Reverses the Disease Phenotype in Recessive Dystrophic Epidermolysis Bullosa Mice.

    PubMed

    Hou, Yingping; Guey, Lin T; Wu, Timothy; Gao, Robert; Cogan, Jon; Wang, Xinyi; Hong, Elizabeth; Ning, Weihuang Vivian; Keene, Douglas; Liu, Nan; Huang, Yan; Kaftan, Craig; Tangarone, Bruce; Quinones-Garcia, Igor; Uitto, Jouni; Francone, Omar L; Woodley, David T; Chen, Mei

    2015-12-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited disorder characterized by skin fragility, blistering, and multiple skin wounds with no currently approved or consistently effective treatment. It is due to mutations in the gene encoding type VII collagen (C7). Using recombinant human C7 (rhC7) purified from human dermal fibroblasts (FB-rhC7), we showed previously that intravenously injected rhC7 distributed to engrafted RDEB skin, incorporated into its dermal-epidermal junction (DEJ), and reversed the RDEB disease phenotype. Human dermal fibroblasts, however, are not used for commercial production of therapeutic proteins. Therefore, we generated rhC7 from Chinese hamster ovary (CHO) cells. The CHO-derived recombinant type VII collagen (CHO-rhC7), similar to FB-rhC7, was secreted as a correctly folded, disulfide-bonded, helical trimer resistant to protease degradation. CHO-rhC7 bound to fibronectin and promoted human keratinocyte migration in vitro. A single dose of CHO-rhC7, administered intravenously into new-born C7-null RDEB mice, incorporated into the DEJ of multiple skin sites, tongue and esophagus, restored anchoring fibrils, improved dermal-epidermal adherence, and increased the animals' life span. Furthermore, no circulating or tissue-bound anti-C7 antibodies were observed in the mice. These data demonstrate the efficacy of CHO-rhC7 in a preclinical murine model of RDEB. PMID:26203639

  9. Human cord blood-derived unrestricted somatic stem cells promote wound healing and have therapeutic potential for patients with recessive dystrophic epidermolysis bullosa.

    PubMed

    Liao, Yanling; Itoh, Munenari; Yang, Albert; Zhu, Hongwen; Roberts, Samantha; Highet, Alexandra M; Latshaw, Shaun; Mitchell, Kelly; van de Ven, Carmella; Christiano, Angela; Cairo, Mitchell S

    2014-03-01

    Human umbilical cord blood (CB)-derived unrestricted somatic stem cells (USSCs) have previously been demonstrated to have a broad differentiation potential and regenerative beneficial effects when administered in animal models of multiple degenerative diseases. Here we demonstrated that USSCs could be induced to express genes that hallmark keratinocyte differentiation. We also demonstrated that USSCs express type VII collagen (C7), a protein that is absent or defective in patients with an inherited skin disease, recessive dystrophic epidermolysis bullosa (RDEB). In mice with full-thickness excisional wounds, a single intradermal injection of USSCs at a 1-cm distance to the wound edge resulted in significantly accelerated wound healing. USSC-treated wounds displayed a higher density of CD31(+) cells, and the wounds healed with a significant increase in skin appendages. These beneficial effects were demonstrated without apparent differentiation of the injected USSCs into keratinocytes or endothelial cells. In vivo bioluminescent imaging (BLI) revealed specific migration of USSCs modified with a luciferase reporter gene, from a distant intradermal injection site to the wound, as well as following systemic injection of USSCs. These data suggest that CB-derived USSCs could significantly contribute to wound repair and be potentially used in cell therapy for patients with RDEB. PMID:23394106

  10. Gene-Corrected Fibroblast Therapy for Recessive Dystrophic Epidermolysis Bullosa using a Self-Inactivating COL7A1 Retroviral Vector.

    PubMed

    Jacków, Joanna; Titeux, Matthias; Portier, Soizic; Charbonnier, Soëli; Ganier, Clarisse; Gaucher, Sonia; Hovnanian, Alain

    2016-07-01

    Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack type VII collagen and therefore have severely impaired dermal-epidermal stability causing recurrent skin and mucosal blistering. There is currently no specific approved treatment for RDEB. We present preclinical data showing that intradermal injections of genetically corrected patient-derived RDEB fibroblasts using a Good Manufacturing Practices grade self-inactivating COL7A1 retroviral vector reverse the disease phenotype in a xenograft model in nude mice. We obtained 50% transduction efficiency in primary human RDEB fibroblasts with an average low copy number (range = 1-2) of integrated provirus. Transduced fibroblasts showed strong type VII collagen re-expression, improved adhesion properties, normal proliferative capabilities, and viability in vitro. We show that a single intradermal injection of 3 × 10(6) genetically corrected RDEB fibroblasts beneath RDEB skin equivalents grafted onto mice allows type VII collagen deposition, anchoring fibril formation at the dermal-epidermal junction, and improved dermal-epidermal adherence 2 months after treatment, supporting functional correction in vivo. Gene-corrected fibroblasts previously showed no tumorigenicity. These data show the efficacy and safety of gene-corrected fibroblast therapy using a self-inactivating vector that has now been good manufacturing grade-certified and pave the way for clinical translation to treat nonhealing wounds in RDEB patients. PMID:26994967

  11. Novel sporadic and recurrent mutations in KRT5 and KRT14 genes in Polish epidermolysis bullosa simplex patients: further insights into epidemiology and genotype-phenotype correlation.

    PubMed

    Wertheim-Tysarowska, K; Ołdak, M; Giza, A; Kutkowska-Kaźmierczak, A; Sota, J; Przybylska, D; Woźniak, K; Śniegórska, D; Niepokój, K; Sobczyńska-Tomaszewska, A; Rygiel, A M; Płoski, R; Bal, J; Kowalewski, C

    2016-05-01

    Epidermolysis bullosa simplex (EBS) is a hereditary genodermatosis characterised by trauma-induced intraepidermal blistering of the skin. EBS is mostly caused by mutations in the KRT5 and KRT14 genes. Disease severity partially depends on the affected keratin type and may be modulated by mutation type and location. The aim of our study was to identify the molecular defects in KRT5 and KRT14 in a cohort of 46 Polish and one Belarusian probands with clinical suspicion of EBS and to determine the genotype-phenotype correlation. The group of 47 patients with clinical recognition of EBS was enrolled in the study. We analysed all coding exons of KRT5 and KRT14 using Sanger sequencing. The pathogenic status of novel variants was evaluated using bioinformatical tools, control group analysis (DNA from 100 healthy population-matched subjects) and probands' parents testing. We identified mutations in 80 % of patients and found 29 different mutations, 11 of which were novel and six were found in more than one family. All novel mutations were ascertained as pathogenic. In the majority of cases, the most severe genotype was associated with mutations in highly conserved regions. In some cases, different inheritance mode and clinical significance, than previously reported by others, was observed. We report 11 novel variants and show novel genotype-phenotype correlations. Our data give further insight into the natural history of EBS molecular pathology, epidemiology and mutation origin. PMID:26432462

  12. Molecular analysis of the human laminin alpha3a chain gene (LAMA3a): a strategy for mutation identification and DNA-based prenatal diagnosis in Herlitz junctional epidermolysis bullosa.

    PubMed

    Pulkkinen, L; Cserhalmi-Friedman, P B; Tang, M; Ryan, M C; Uitto, J; Christiano, A M

    1998-09-01

    Mutations in the genes (LAMA3, LAMB3, and LAMC2) encoding the subunit polypeptides of the cutaneous basement membrane zone protein laminin 5 have been reported in different forms of junctional epidermolysis bullosa (JEB), an inherited blistering skin disease. In this study, we present the complete exon-intron organization of the "a" transcript of the laminin alpha3 chain gene, LAMA3a, which is expressed primarily in the skin. We have performed fine-resolution mapping of this gene on chromosome 18q11.2 using a human-hamster radiation hybrid panel. We have also developed a mutation-detection strategy based on the exon-intron structure of LAMA3a. This strategy, based on PCR amplification of genomic sequences, followed by heteroduplex scanning and automated nucleotide sequencing, was used for successful mutation screening in a family with the lethal (Herlitz) type of JEB, and two novel LAMA3 mutations were identified in the proband. The mutations consisted of a single-base pair deletion in LAMA3a exon A11 on the paternal allele, designated 1239delC, and a two-base pair deletion in LAMA3a exon A23 on the maternal allele, designated 2959delGG. This information was also used for DNA-based prenatal testing in a subsequent pregnancy in this family. Collectively, these results attest to our expanding capability to elucidate the genetic basis of various forms of epidermolysis bullosa using molecular techniques. PMID:9759651

  13. The Effects of Septal Deviation, Concha Bullosa, and Their Combination on the Depth of Posterior Palatal Arch in Cone-Beam Computed Tomography

    PubMed Central

    Dalili Kajan, Zahra; Khademi, Jalil; Nemati, Somayeh; Niksolat, Elmira

    2016-01-01

    Statement of the Problem Nasal breathing is the major pattern of air intake. Changes in breathing pattern alter the posture of the head, jaws and tongue that could change pressure on the jaw and teeth and affect their growth. Purpose This study aimed to investigate the relationship between septal deviations (SD) per se and in combination with concha bullosa (CB) on maxilla; particularly the depth of palatal arch. Materials and Method This descriptive-comparative study was performed on 116 cone-beam computed tomography (CBCT) images. The images were categorized into four groups (n=29) as follows; group 1: SD+CB, group 2: only SD, group 3: neither SD nor CB, and group 4: only CB. In coronal images, deviated septal length (DSL), angle of deviated septal curve (DSCA), palatal arch depth (PAD), palatal interalveolar length (PIL), PAD/PIL ratio, septal vertical length (SVL), maxillopalatal arch angle (MPAA), interjugum distance (IJD), and jugum angle (JA) were measured. The data were statistically analyzed with Tukey's HSD and Chi-square tests. Results There were statistically significant differences in DSL and DSCA (p= 0.0001) among the four groups. The study groups were not statistically different regarding the IJD, JA, MPAA, PAD/PIL, PAD, PIL, and SVL. However, in group 1, PAD/PIL were significantly correlated with DSCA and DSL (p= 0.037, and p= 0.043, respectively). Conclusion Based on the findings of this study, simultaneous occurrence of SD and CB influenced the depth and curve of the palatal bone. The PAD/PIL ratio was negatively correlated with the DSCA angle. This correlation was associated with a decrease in PAD, indicating that concurrent occurrence of SD and CB remarkably affected the palatal base of maxilla. PMID:26966705

  14. Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation.

    PubMed Central

    Hovnanian, A; Rochat, A; Bodemer, C; Petit, E; Rivers, C A; Prost, C; Fraitag, S; Christiano, A M; Uitto, J; Lathrop, M; Barrandon, Y; de Prost, Y

    1997-01-01

    We have characterized 21 mutations in the type VII collagen gene (COL7A1) encoding the anchoring fibrils, 18 of which were not previously reported, in patients from 15 unrelated families with recessive dystrophic epidermolysis bullosa (RDEB). COL7A1 mutations in both alleles were identified by screening the 118 exons of COL7A1 and flanking intron regions. Fourteen mutations created premature termination codons (PTCs) and consisted of nonsense mutations, small insertions, deletions, and splice-site mutations. A further seven mutations predicted glycine or arginine substitutions in the collagenous domain of the molecule. Two mutations were found in more than one family reported in this study, and six of the seven missense mutations showed clustering within exons 72-74 next to the hinge region of the protein. Patients who were homozygous or compound heterozygotes for mutations leading to PTCs displayed both absence or drastic reduction of COL7A1 transcripts and undetectable type VII collagen protein in skin. In contrast, missense mutations were associated with clearly detectable COL7A1 transcripts and with normal or reduced expression of type VII collagen protein at the dermo/epidermal junction. Our results provide evidence for at least two distinct molecular mechanisms underlying defective anchoring fibril formation in RDEB: one involving PTCs leading to mRNA instability and absence of protein synthesis, the other implicating missense mutations resulting in the synthesis of type VII collagen polypeptide with decreased stability and/or altered function. Genotype-phenotype correlations suggested that the nature and location of these mutations are important determinants of the disease phenotype and showed evidence for interfamilial phenotypic variability. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 PMID:9326325

  15. Novel and recurrent mutations in the laminin-5 genes causing lethal junctional epidermolysis bullosa: molecular basis and clinical course of Herlitz disease.

    PubMed

    Mühle, Christiane; Jiang, Qiu-Jie; Charlesworth, Alexandra; Bruckner-Tuderman, Leena; Meneguzzi, Guerrino; Schneider, Holm

    2005-01-01

    Herlitz disease (H-JEB), the lethal form of junctional epidermolysis bullosa, is a rare genodermatosis presenting from birth with widespread erosions and blistering of skin and mucosae because of tissue cleavage within the epidermal basement membrane. Mutations in any of the three genes encoding the alpha3, beta3 and gamma2 chains of laminin-5 underlie this recessively inherited disorder. Here, we report the molecular basis and clinical course of H-JEB in 12 patients. Two novel nonsense mutations in the gene LAMA3 (E281X and K1299X) and a novel frame-shift mutation in the gene LAMB3 (1628insG) leading to a premature termination codon were identified by DNA sequencing and confirmed by restriction fragment length polymorphism analysis. In the four patients affected, neither the resulting truncated polypeptide chains nor assembled laminin-5 protein were detectable by immunofluorescence. Three patients were found to be heterozygous for the known hotspot mutation R635X and the recurrent mutations Q373X or 29insC in the gene LAMB3, whereas five others were homozygous for R635X. Significant variations in the disease progression and survival times between 1 and 30 months in this group of H-JEB patients emphasised the impact of modifying factors and the importance of immunostaining or mRNA assessment as parallel diagnostic methods. Interestingly, the only patients who survived for longer than 6 months were four females carrying the mutation R635X homozygously. In one of them, the clinical course may have been improved by treatment with artificial skin equivalents. These data may stimulate further investigation of genotype-phenotype correlations and facilitate mutation analysis and genetic counselling of affected families. PMID:15538630

  16. Predominance of the recurrent mutation R635X in the LAMB3 gene in European patients with Herlitz junctional epidermolysis bullosa has implications for mutation detection strategy.

    PubMed

    Pulkkinen, L; Meneguzzi, G; McGrath, J A; Xu, Y; Blanchet-Bardon, C; Ortonne, J P; Christiano, A M; Uitto, J

    1997-08-01

    Junctional forms of epidermolysis bullosa (JEB) are characterized by tissue separation at the level of the lamina lucida. We have recently disclosed specific mutations in the LAMA3, LAMB3, and LAMC2 genes encoding the subunit polypeptides of the anchoring filament protein laminin 5 in 66 families with different variants of JEB. Examination of the JEB mutation database revealed recurrence of a particular C-->T substitution at nucleotide position 1903 (exon 14) of LAMB3, resulting in the mutation R635X. The inheritance of this nonsense mutation was noted on different genetic backgrounds, suggesting that R635X is a hotspot mutation. In this study, we have performed mutation evaluation in a European cohort of 14 families with the lethal, Herlitz type of JEB (H-JEB). The families were first screened for the presence of the R635X mutation by restriction enzyme digestion of the PCR product corresponding to exon 14. Four of the probands were found to be homozygous and six were heterozygous for R635X. The remaining alleles were subjected to mutation screening by PCR amplification of individual exons of LAMB3 and LAMC2, followed by heteroduplex analysis and nucleotide sequencing. In three families (six alleles), mutations in LAMC2 were disclosed. In the remaining eight alleles, additional pathogenetic LAMB3 mutations were found. None of the patients had LAMA3 mutation. Thus, LAMB3 mutations accounted for 22 of 28 JEB alleles (79%), and a total of 14 of 22 LAMB3 alleles (64%) harbored the R635X mutation, signifying its prevalence as a predominant genetic lesion underlying H-JEB in this European cohort of patients. This recurrent mutation will facilitate screening of additional JEB patients for the purpose of prenatal testing of fetuses at risk for recurrence. PMID:9242513

  17. Skin cancer and photoaging in ethnic skin.

    PubMed

    Halder, Rebat M; Ara, Collette J

    2003-10-01

    Skin cancer prevalence in ethnic skin is low. Squamous cell carcinoma, hypopigmented mycosis fungoides, and acral lentiginous melanoma are the most serious types of skin cancer noted in the darker-skinned population. Photoaging occurs less frequently and is less severe in ethnic skin. PMID:14717413

  18. Compound heterozygosity for COL7A1 mutations in twins with dystrophic epidermolysis bullosa: A recessive paternal deletion/insertion mutation and a dominant negative maternal glycine substitution result in a severe phenotype

    SciTech Connect

    Christiano, A.M.; Uitto, J.; Anton-Lamprecht, I.; Ebschner, U.; Amano, S.; Burgeson, R.E.

    1996-04-01

    We have previously demonstrated genetic linkage between the type VII collagen gene (COL7A1) and the dominant (DDEB) and recessive (RDEB) forms of dystrophic epidermolysis bullosa (DEB) and have subsequently identified pathogenetic mutations in several families. Mutations in DDEB identified thus far are glycine substitutions in the collagenous domain of COL7A1, while the most severe forms of RDEB result from premature termination codon (PTC) mutations on both alleles. In this study, we performed mutation analysis in the COL7A1 gene in twins who displayed a severe DEB phenotype. Mutational analysis revealed a paternal 2-bp deletion/1-bp insertion in exon 56, designated 5103CC{yields}G, which results in a frameshift and downstream PTC. Analysis of the maternal COL7A1 allele revealed a glycine-to-arginine substitution in exon 91 (G2351R). Careful questioning of the mother revealed that she and her father had a history of shedding of toenails and occasional poorly heating erosions, consistent with a mild form of DDEB. Immunoprecipitation of type VII collagen from fibroblasts of the twins revealed a marked reduction in intracellular protein production, consistent with the drastic reduction in mRNA transcript from the paternal mutant allele, while the majority of polypeptides bearing the glycine substitution appeared to be degraded intracellularly. Thus, the severe RDEB phenotype in the probands results from compound heterozygosity for one glycine substitution and one PTC mutation in COL7A1. 40 refs., 7 figs.

  19. The genes for nicein/kalinin 125- and 100-kDa subunits, candidates for junctional epidermiolysis bullosa, map to chromosomes 1q32 and 1q25-q31

    SciTech Connect

    Vailly, J.; Ortonne, J.P.; Meneguzzi, G.; Szepetowski, P.; Pedeutour, F. ); Mattei, M.G. ); Burgeson, R. )

    1994-05-01

    Expression of nicein is specifically hampered in the severe form of junctional epidermolysis bullosa (JEB), a recessive genodermatosis characterized by blister formation of integument believed to be due to defects in hemidesmosomes. Nicein genes are therefore the prime candidates for involvement in JEB. To map the gene encoding the 125-kDa subunit of nicein, the authors used the cDNA Kal5.5C coding for the amino-terminal domain of the protein. In situ hybridization was carried out on chromosomes in phytohemagglutinin-stimulated blood lymphocytes of healthy donors. In 100 metaphases examined, 153 silver grains were found associated with chromosomes; 45 (29%) of these were located on chromosome 1, and 33 (73%) of these 45 grains mapped to region 1q32.1-q41 with a maximum in band 1q32. To confirm the regional localization of the genes for nicein subunits of 100 and 125 kDa, fluorescence in situ hybridization was performed on normal lymphocytes from two unrelated normal males and fibroblast cell lines GM00257 (karyotype 46,XX, t(1;2)(1q32;2p23)) and GM004088 (46,XY,t(1;4)(q32;p16)). It was thus confirmed that the genes for nicein 125- and 100-kDa subunits are localized at 1q32 and 1q25-q31, respectively. 9 refs., 1 fig.

  20. A mycosis-like granuloma of fish

    USGS Publications Warehouse

    Wood, E.M.; Yasutake, W.T.; Lehman, W.L.

    1955-01-01

    Mycoses of systemic distribution are rarely observed in fresh-water fish in this country. In a recent review of atypical cell growths in fishes, Nigrelli cited the only known instance of a mycetoma in a North American fresh-water fish which occurred in the head of fingerling landlocked salmon from an Idaho hatchery. The fungus associated with this granuloma was characterized by a branching septate mycelium. Rucker reported a streptomycete which was pathogenic to blueblack salmon. This organism produced internal nodules containing masses of hyphae but no inflammatory response. A pathogenic fungus has been observed frequently in marine fish, however, and in both marine and fresh-water fish in Europe. This organism was tentatively classified as a Phycomycete in or near the order Chytridiales and was assigned to the genus and species Ichthyophonus hoferi, later reclassified as Ichthyosporidium hoferi. The graduloma described in this report occurs in fresh-water trout and is apparently caused by a budding, yeast-like form with no hyphae which evokes a tremendous inflammatory reaction. Morphologically, the organism does not resemble the previously described Ichthyosporidium. The lesions were first seen accidentally in sections prepared from a diplobacillus infection of brook trout termed “kidney disease.” Subsequently, the granuloma was observed in three widely separated infections involving the diplobacillus in each instance.The histological material was received in a fixed condition; thus, no cultural data was available and the nomenclature and classification of the mycotic organism were not attempted. The present distribution of the disease, however, with its potential threat to domestic fish populations, seemed to warrant a description and discussion of the disease. Efforts are in progress to culture the organism.

  1. [Gas-forming mycosis of the kidney].

    PubMed

    Vorreuther, R; Kuss, M; Franzen, W; Engelking, R; Altenburg, A

    1993-01-01

    We report on the case of a 22-year-old heroin-dependent diabetic woman. She presented with a gas-forming fungal infection of the kidney caused by Candida tropicalis. The patient was successfully treated by conservative means. Problems in the diagnosis and therapy of this rare disease are discussed. PMID:8447045

  2. Individualized eye shields for use in electron beam therapy as well as low-energy photon irradiation

    SciTech Connect

    Asbell, S.O.; Siu, J.; Lightfoot, D.A.; Brady, L.W.

    1980-04-01

    Thin lead eye shields formed with a rubber hammer over smooth wooden mandril and coated with dental acrylic have been used on 25 patients undergoing electron beam treatment for mycosis fungoides or superficial x-ray irradiation with no significant difficulties. The shields may be fabricated in less than two hours and exactly fit the contour and size of the eye. Details of the fabrication process and evaluation of the shielding effectiveness are presented.

  3. [A girl with hypopigmented skin lesions].

    PubMed

    Martens, Bibi; Abdul Hamid, Myrurgia; Martens, Herm

    2014-01-01

    A 9-year-old girl visited the department of Dermatology with an asymptomatic hypopigmented skin eruption on her upper legs, groins and trunk since 7 years. Histopathological analysis established the diagnosis of hypopigmented mycosis fungoides, a rare subtype of cutaneous T-cell lymphoma which is most commonly seen at younger age. The lesions are successfully treated with clobetasol 0.05% ointment 4 days a week. PMID:25027222

  4. Ichthyosiform Large Plaque Parapsoriasis: Report of a Rare Entity

    PubMed Central

    Nag, Falguni; Ghosh, Arghyaprasun; Biswas, Projna; Chatterjee, Gobinda; Biswas, Saugato

    2013-01-01

    Large plaque parapsoriasis (LPP) is an idiopathic, chronic scaly dermatosis classified within parapsoriasis group of diseases, occurring commonly in middle aged patients of all races and geographic regions. LPP and its variants are closely related to the patch stage of mycosis fungoides. The two types of LPP mostly described are the poikilodermatous and retiform parapsoriasis. We are reporting an ichthyosiform LPP for its rarity. PMID:24082186

  5. The Use of Interferons in the Treatment of Cutaneous T-Cell Lymphoma.

    PubMed

    Spaccarelli, Natalie; Rook, Alain H

    2015-10-01

    Interferons are polypeptides that naturally occur in the human body as a part of the innate immune response. By harnessing these immunomodulatory functions, synthetic interferons have shown efficacy in combating various diseases including cutaneous T-cell lymphoma. This article closely examines the qualities of interferon alfa and interferon gamma and the evidence behind their use in the 2 most common types of cutaneous T-cell lymphomas, namely, mycosis fungoides and Sézary syndrome. PMID:26433845

  6. Bortezomib and Azacitidine in Treating Patients With Relapsed or Refractory T-Cell Lymphoma

    ClinicalTrials.gov

    2013-12-02

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Small Intestine Lymphoma; T-cell Large Granular Lymphocyte Leukemia

  7. Clinical implementation of total skin electron irradiation treatment with a 6 MeV electron beam in high-dose total skin electron mode

    NASA Astrophysics Data System (ADS)

    Lucero, J. F.; Rojas, J. I.

    2016-07-01

    Total skin electron irradiation (TSEI) is a special treatment technique offered by modern radiation oncology facilities, given for the treatment of mycosis fungoides, a rare skin disease, which is type of cutaneous T-cell lymphoma [1]. During treatment the patient's entire skin is irradiated with a uniform dose. The aim of this work is to present implementation of total skin electron irradiation treatment using IAEA TRS-398 code of practice for absolute dosimetry and taking advantage of the use of radiochromic films.

  8. Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas.

    PubMed

    de Masson, Adèle; Beylot-Barry, Marie; Bouaziz, Jean-David; Peffault de Latour, Régis; Aubin, François; Garciaz, Sylvain; d'Incan, Michel; Dereure, Olivier; Dalle, Stéphane; Dompmartin, Anne; Suarez, Felipe; Battistella, Maxime; Vignon-Pennamen, Marie-Dominique; Rivet, Jacqueline; Adamski, Henri; Brice, Pauline; François, Sylvie; Lissandre, Séverine; Turlure, Pascal; Wierzbicka-Hainaut, Ewa; Brissot, Eolia; Dulery, Rémy; Servais, Sophie; Ravinet, Aurélie; Tabrizi, Reza; Ingen-Housz-Oro, Saskia; Joly, Pascal; Socié, Gérard; Bagot, Martine

    2014-03-01

    The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38-0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41-0.77) and progression-free survival 31% (95%CI: 0.19-0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1-0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3-6.2; P=0.01) but also transplant-related mortality (HR=10(-7), 95%CI: 4.10(-8)-2.10(-7); P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides. PMID:24213148

  9. Romidepsin: evidence for its potential use to manage previously treated cutaneous T cell lymphoma

    PubMed Central

    Poligone, Brian; Lin, Janet; Chung, Catherine

    2011-01-01

    Introduction: Cutaneous T cell lymphoma (CTCL) encompasses a heterogeneous group of neoplasms of skin-homing T cells, which includes mycosis fungoides, the most common form, and Sézary syndrome, the leukemia equivalent of mycosis fungoides. Histone deacetylase inhibitors are currently under investigation for their therapeutic value in a variety of conditions. Through multiple mechanisms, they induce apoptosis or inhibition of tumor cell growth. Some studies have also shown histone deacetylase inhibitors to have synergistic activity with existing therapeutic agents in selected conditions. Romidepsin is a histone deacetylase inhibitor with a promising efficacy and safety profile that may represent a valuable treatment alternative for patients with treatment-resistant mycosis fungoides and Sézary syndrome. Aims: To review emerging evidence regarding the use of romidepsin in the management of treatment-resistant CTCL. Evidence review: There is evidence that romidepsin can induce significant and durable responses in patients with refractory CTCL. In two independent Phase II trials including a total of 167 patients with CTCL, there was an overall response rate of 34% with a partial response of 28% and complete response rate of 6%. The most frequent toxicities reported from the Phase II trials were nausea, vomiting, fatigue, anorexia, and dysgeusia. Clinical potential: Romidepsin may be an effective therapeutic option for patients with CTCL who have had treatment failure with multiple standard treatment modalities. PMID:21468238

  10. Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas

    SciTech Connect

    Neelis, Karen J. Schimmel, Erik C.; Vermeer, Maarten H.; Senff, Nancy J.; Willemze, Rein; Noordijk, Evert M.

    2009-05-01

    Purpose: To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). Methods and Materials: A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. Results: The complete response rate for CBCL lesions was 72%. Of the 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Conclusion: Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.

  11. Osteonecrosis of the Jaw in Association With Chemotherapy in the Setting of Cutaneous T-Cell Lymphoma.

    PubMed

    DeSesa, Christopher R; Appugounder, Suganya; Haberland, Christel; Johnson, Michael P

    2016-02-01

    T-cell lymphomas (TCLs) account for approximately 15 to 20% of all non-Hodgkin lymphomas in the United States. The most common form of TCL is cutaneous TCL (CTCL), with Sézary syndrome and mycosis fungoides being the most prevalent subtypes. Sézary syndrome is the more aggressive form and often is referred to as a late-stage variant of mycosis fungoides. Clinically, it is characterized by diffuse erythroderma, cutaneous edema, pruritus, nonhealing cutaneous ulcers, and lymphadenopathy. Patients also can present with changes to their nails, hyperpigmentation, alopecia, palmoplantar keratoderma, ectropion, and hepatosplenomegaly. The overall prognosis for patients with Sézary syndrome is poor. The literature regarding oral manifestations of CTCL mostly report those of mycosis fungoides because it is the most common subtype of CTCL. Currently, there are only 2 reports in the scientific literature of intraoral manifestations of Sézary syndrome. This case report describes a patient with Sézary syndrome who presented with rapidly progressing erythematous lesions of the gingiva and multifocal osteonecrosis of the maxilla and mandible. This is the third reported case of an intraoral manifestation of Sézary syndrome and the first reported case of osteonecrosis in the setting of CTCL. PMID:26296596

  12. Genetics Home Reference: dystrophic epidermolysis bullosa

    MedlinePlus

    ... protein that is used to assemble type VII collagen. Collagens are molecules that give structure and strength to ... tendons, and ligaments, throughout the body. Type VII collagen plays an important role in strengthening and stabilizing ...

  13. Genetics Home Reference: junctional epidermolysis bullosa

    MedlinePlus

    ... protein that is used to assemble type XVII collagen. Collagens are molecules that give structure and strength to ... tendons, and ligaments, throughout the body. Type XVII collagen helps attach the epidermis to underlying layers of ...

  14. Genetics Home Reference: epidermolysis bullosa simplex

    MedlinePlus

    ... problems. Severe cases may be life-threatening in infancy. Researchers have identified four major types of epidermolysis ... blisters that appear at birth or in early infancy. The blistering tends to be less severe than ...

  15. Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas

    ClinicalTrials.gov

    2015-04-28

    ; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III

  16. Cilengitide (EMD 121974) in Treating Patients With Advanced Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-01-23

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2

  17. 17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2013-01-24

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenstr

  18. Lenalidomide as Maintenance Therapy After Combination Chemotherapy With or Without Rituximab and Stem Cell Transplant in Treating Patients With Persistent or Recurrent Non-Hodgkin Lymphoma That is Resistant to Chemotherapy

    ClinicalTrials.gov

    2014-12-02

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  19. CPI-613 and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-07-26

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia

  20. A case of syringotropic cutaneous T-cell lymphoma treated with local radiotherapy.

    PubMed

    Jacob, Rojymon; Scala, Matthew; Fung, Maxwell A

    2009-01-01

    Syringotropic cutaneous T-cell lymphoma (SCTCL) is a variant of mycosis fungoides that is characterized by the presence of lymphocytic infiltration of eccrine glandular structures and the absence of the classic features of MF, such as epidermotropism and Pautrier's microabscesses. We report a patient with SCTCL who presented with multiple hypopigmented patches and localized alopecia who was treated with local radiotherapy with excellent local control. In our experience, local electron radiation offers local control in early stage SCTCL, and it may be possible to reserve systemic therapy for more advanced stages of the disease. PMID:19103368

  1. Leukoderma associated with Sézary syndrome: a rare presentation.

    PubMed

    Tang, Mark; Tan, Suat Hoon; Lim, Lay Cheng

    2003-11-01

    We describe a patient with Sézary syndrome who was initially seen with the rare occurrence of both generalized erythroderma and extensive leukoderma of his lower limbs. Apart from the absence of melanocytes in the leukodermic skin, histopathologic features of both areas were identical, showing an infiltrate of atypical lymphocytes with epidermotropism. This form of Sézary syndrome-associated leukoderma is clinically distinguishable from hypopigmented mycosis fungoides in which hypopigmented lesions are the sole manifestation of the cutaneous T-cell lymphoma. PMID:14576642

  2. Clinicopathological correlation of acquired hypopigmentary disorders.

    PubMed

    Patel, Anisha B; Kubba, Raj; Kubba, Asha

    2013-01-01

    Acquired hypopigmentary disorders comprise a significant group of disorders that affect Indians and Asians. The pigment disturbance in darker skin individuals can be very distressing to the patient and the family. These disorders cover a wide array of pathologies including infections, autoimmune processes, lymphoproliferative disorders, and sclerosing diseases. Histological diagnosis is particularly important because treatments for these diseases are varied and specific. This review will focus on histopathological diagnosis based on clinicopathological correlation for commonly encountered disorders such as leprosy, vitiligo, lichen sclerosus, pityriasis alba (PA), and pityriasis versicolor (PV). Atypical or uncommon clinical presentation of classic diseases such as hypopigmented mycosis fungoides (HMF) and hypopigmented sarcoidosis are also included. PMID:23619442

  3. Panobinostat in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-04-18

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  4. Animals Eponyms in Dermatology

    PubMed Central

    Jindal, Nidhi; Jindal, Pooja; Kumar, Jeevan; Gupta, Sanjeev; Jain, VK

    2014-01-01

    The world of Dermatology is flooded with inflexions among clinical conditions and signs and syndromes; making it interesting, but a tougher subject to remember. Signs and syndromes have always fascinated residents, but simultaneously burdened their minds, as these attractive names are difficult to remember. This work was undertaken to review dermatological conditions and signs based on commonly encountered daily words and objects like animals, etc. Fifty dermatological conditions were found to be based on animal eponyms. For example, the usage of animal terminology in dermatology like leonine facies is present in leprosy, sarcoidosis, mycosis fungoides (MF), and airborne contact dermatitis (ABCD). PMID:25484417

  5. The differential diagnosis of atopic dermatitis in childhood.

    PubMed

    Krol, Alfons; Krafchik, Bernice

    2006-01-01

    Atopic is the most common of the dermatitides seen in infancy and childhood, but there are numerous other diseases that can mimic the skin findings. These include seborrheic dermatitis, immunodeficiency, and psoriasis in infancy; scabies, tinea corporis infection, perioral, nummular, contact, and molluscum dermatitis in childhood. It is sometimes extremely difficult to differentiate between ichthyosis and AD, and it is also important to differentiate AD from erythrodermic conditions including acrodermatitis enteropathica, biotin deficiency, and Netherton syndrome. A rare condition in children that may mimic AD is mycosis fungoides. PMID:16669989

  6. Interleukin-12 in Treating Patients With Previously Treated Non-Hodgkin's Lymphoma or Hodgkin's Disease

    ClinicalTrials.gov

    2015-04-14

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  7. Skin-Directed Therapies in Cutaneous T-Cell Lymphoma.

    PubMed

    Nguyen, Cuong V; Bohjanen, Kimberly A

    2015-10-01

    Early stage mycosis fungoides represents the most common clinical presentation of cutaneous lymphoma, with skin-directed therapies long established in its treatment. These therapies continue to change as new treatment regimens emerge. Other skin-directed treatments include light and radiation therapy. Therapies with higher levels of evidence and less systemic toxicity are usually preferred as first-line treatment. However, even these established therapies, like topical corticosteroids and carmustine, lack randomized clinical trials to establish their efficacy. Research is also needed to further define the role of combination topical therapies and how skin-directed therapies can be used as adjuvants to systemic medications. PMID:26433841

  8. Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-04-18

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  9. Total skin electron irradiation techniques: a review

    PubMed Central

    Milecki, Piotr; Skórska, Małgorzata; Fundowicz, Dorota

    2013-01-01

    Total skin electron irradiation (TSEI) has been employed as one of the methods of mycosis fungoides treatment since the mid-twentieth century. In order to improve the effects and limit the complications following radiotherapy, a number of varieties of the TSEI method, frequently differing in the implementation mode have been developed. The paper provides a systematic review of the different varieties of TSEI. The discussed differences concerned especially: (i) technological requirements and geometric conditions, (ii) the alignment of the patient, (iii) the number of treatment fields, and (iv) dose fractionation scheme. PMID:24278046

  10. Dose Monitoring of Busulfan and Combination Chemotherapy in Hodgkin or Non-Hodgkin Lymphoma Undergoing Stem Cell Transplant

    ClinicalTrials.gov

    2015-08-12

    Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Childhood Anaplastic Large

  11. An overview of cutaneous T cell lymphomas

    PubMed Central

    Bagherani, Nooshin; Smoller, Bruce R.

    2016-01-01

    Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are characterized by a cutaneous infiltration of malignant monoclonal T lymphocytes. They typically afflict adults with a median age of 55 to 60 years, and the annual incidence is about 0.5 per 100,000. Mycosis fungoides, Sézary syndrome, and primary cutaneous peripheral T cell lymphomas not otherwise specified are the most important subtypes of CTCL. CTCL is a complicated concept in terms of etiopathogenesis, diagnosis, therapy, and prognosis. Herein, we summarize advances which have been achieved in these fields. PMID:27540476

  12. Actinic reticuloid

    SciTech Connect

    Marx, J.L.; Vale, M.; Dermer, P.; Ragaz, A.; Michaelides, P.; Gladstein, A.H.

    1982-09-01

    A 58-year-old man has his condition diagnosed as actinic reticuloid on the basis of clinical and histologic findings and phototesting data. He had clinical features resembling mycosis fungoides in light-exposed areas. Histologic findings disclosed a bandlike infiltrate with atypical mononuclear cells in the dermis and scattered atypical cells in the epidermis. Electron microscopy disclosed mononuclear cells with bizarre, convoluted nuclei, resembling cerebriform cells of Lutzner. Phototesting disclosed a diminished minimal erythemal threshold to UV-B and UV-A. Microscopic changes resembling actinic reticuloid were reproduced in this patient 24 and 72 hours after exposure to 15 minimal erythemal doses of UV-B.

  13. (1→3)-β-D-glucanemia in deep mycosis

    PubMed Central

    Obayashi, Taminori

    1997-01-01

    Factor G, a coagulation proenzyme of the Japanese horseshoe crab (Tachypleus tridentatus), is extremely sensitive to (1→3)-β-D-glucan, which is a characteristic cell-wall constituent of fungi. Using this factor and by a digestion study with (1→3)-β-D-glucan, we showed that blood from patients with deep m ycosis contains the glucan. It was detected in 39 out of 41 fungal febrile episodes (sensitivity 90%), but in none of the 59 nonfungal febrile episodes (specificity 100%). PMID:18472857

  14. Airway Surface Mycosis in Chronic Th2-Associated Airway Disease

    PubMed Central

    Porter, Paul; Lim, Dae Jun; Maskatia, Zahida Khan; Mak, Garbo; Tsai, Chu-Lin; Citardi, Martin J; Fakhri, Samer; Shaw, Joanne L.; Fothergil, Annette; Kheradmand, Farrah; Corry, David B; Luong, Amber

    2014-01-01

    Background Environmental fungi have been linked to T helper type 2 (Th2) cell-related airway inflammation and the Th2-associated chronic airway diseases asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. Objective To determine the frequency of fungus isolation and fungus-specific immunity in Th2-associated and non-associated airway disease patients. Methods Sinus lavage fluid and blood were collected from sinus surgery patients (n=118) including CRS patients with and without nasal polyps and AFRS and non-CRS/non-asthmatic control patients. Asthma status was deteremined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. Peripheral blood mononuclear cells were restimulated with fungal antigens in an enzyme linked immunocell spot (ELISpot) assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared to fungus-specific IgE levels measured from plasma by ELISA. Results Filamentous fungi were significantly more commonly cultured from Th2-associated airway disease subjects (asthma, CRSwNP, or AFRS: n=68) compared to non-Th2-associated control patients (n=31); 74% vs 16% respectively, p<0.001. Both fungus-specific IL-4 ELISpot (n=48) and specific IgE (n=70) data correlated with Th2-associated diseases (sensitivity 73% and specificity 100% vs. 50% and 77%, respectively). Conclusions The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with Th2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients. Clinical Implications Airway fungi may contribute to the expression of sinusitis with nasal polyps and asthma, suggesting that efforts to eradicate fungi from the airways and environments of these patients should be considered. PMID:24928648

  15. Cutaneous and pulmonary mycosis in green anacondas (Euncectes murinus).

    PubMed

    Miller, Debra L; Radi, Zaher A; Stiver, Shane L; Thornhill, Timothy D

    2004-12-01

    Two dead, captive green anacondas (Eunectes murinus), including one male and one female, submitted for necropsy were in poor body condition, having multiple, scattered, dark red foci on the scales and mottled lungs. Both snakes had severe mycotic dermatitis. In addition, the male snake had mycotic stomatitis, and the female snake had mycotic pneumonia. Trichophyton sp., Verticillium sp., and Alternaria sp. were isolated from the dermal lesions. The pulmonary lesions were morphologically consistent with Aspergillus sp. Bacterial organisms isolated from skin and internal organs included Chryseobacterium meningosepticum, Stenotrophomonas maltophilia, Aeromonas hydrophila, and Providencia rettgeri. Mycotic diseases can be devastating to reptiles, and suboptimal husbandry and captivity were likely the predisposing factors that led to opportunistic invasion in these snakes. PMID:15732602

  16. Disseminated mycosis in a killer whale (Orcinus orca).

    PubMed

    Abdo, Walied; Kawachi, Takeshi; Sakai, Hiroki; Fukushi, Hideto; Kano, Rui; Shibahara, Tomoyuki; Shirouzu, Hiroshi; Kakizoe, Yuko; Tuji, Hajime; Yanai, Tokuma

    2012-01-01

    Hematological findings in a female killer whale (Orcinus orca) undergoing rehabilitation after sudden severe anorexia revealed continuing increases in serum lactate dehydrogenase and aspartate aminotransferase activities as well as fibrinogen concentration. Serologic evidence of herpesvirus infection and skin vesicles were detected 2 weeks into the treatment regimen of antibiotics and corticosteroids. The whale showed signs of improvement after treatment with anti-herpesvirus drugs, but sudden severe anorexia reappeared, along with marked elevation of fibrinogen concentration that continued until the death. Postmortem examination revealed multiple light tan foci of necrosis in the skeletal and cardiac muscles, and lung consolidation. Microscopic findings indicated disseminated fungal granulomas in the skeletal and cardiac muscles, as well as myocarditis, mycotic embolic thromboarteritis of cardiac blood vessels, and bronchopneumonia with numerous typical Aspergillus-like fungi. Mucor-like structures in granulomas in the heart and skeletal muscle and Aspergillus-like fungi in the lungs were identified using periodic acid-Schiff, Gomori methenamine silver stain, and immunohistochemistry. The present case involves dual infection with Mucor and Aspergillus species in a killer whale with concurrent herpesvirus. PMID:22362957

  17. Lymphoproliferative lesions of the skin

    PubMed Central

    Cerroni, L

    2006-01-01

    Diagnosis and differential diagnosis of cutaneous lymphoproliferative disorders is one of the most difficult areas in dermatopathology, and biopsies are often taken to rule out a cutaneous lymphoma in patients with “unclear” or “therapy‐resistant” skin lesions. Histopathological features alone often enable a given case to be classified to a diagnostic group (eg, epidermotropic lymphomas), but seldom allow a definitive diagnosis to be made. Performing several biopsies from morphologically different lesions is suggested, especially in patients with suspicion of mycosis fungoides. Immunohistochemistry is often crucial for proper classification of the cases, but in some instances is not helpful (eg, early lesions of mycosis fungoides). Although molecular techniques provide new, powerful tools for diagnosing cutaneous lymphoproliferative disorders, results of molecular methods should always be interpreted with the clinicopathological features, keeping in mind the possibility of false positivity and false negativity. In many cases, a definitive diagnosis can be made only on careful correlation of the clinical with the histopathological, immunophenotypical and molecular features. PMID:16873563

  18. Detection of HTLV-1 by polymerase chain reaction in situ hybridization in adult T-cell leukemia/lymphoma.

    PubMed

    Setoyama, M; Kerdel, F A; Elgart, G; Kanzaki, T; Byrnes, J J

    1998-03-01

    A method for nonradioactive polymerase chain reaction in situ hybridization was developed and used to determine the distribution of human T-lymphotropic virus type I (HTLV-I) proviral DNA in paraffin-embedded surgical specimens of adult T-cell leukemia/lymphoma (ATLL). As controls, we used biopsy samples of five cases of mycosis fungoides, cells of an HTLV-I-infected cell line (MT2), as well as HTLV-1-negative cells (YAS). We successfully detected the amplicon of the HTLV-1 tax sequence in the nuclei of the cutaneous infiltrating lymphoid cells in 90% (9/10) of ATLL cases. Studies also revealed the existence of HTLV-1 provirus DNA in nuclei of sweat gland epithelial cells and vascular endothelial cells as well as lymphoid cells in ATLL patients. Mycosis fungoides and YAS cells were negative for the HTLV-I tax sequence, but MT2 cells were strongly positive. The results indicated that this technique was more sensitive in detecting intracellular amplicons than was the previous in situ hybridization method. Through its use, we were able to easily determine the distribution of HTLV-I-positive cells among the various cells and tissues of paraffin-embedded archival materials. PMID:9502410

  19. Blood Sample Markers of Reproductive Hormones in Assessing Ovarian Reserve in Younger Patients With Newly Diagnosed Lymphomas

    ClinicalTrials.gov

    2016-06-06

    Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Hodgkin Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Childhood Small Noncleaved Cell Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage III Childhood Small Noncleaved

  20. Massage Therapy Given by Caregiver in Treating Quality of Life of Young Patients Undergoing Treatment for Cancer

    ClinicalTrials.gov

    2016-07-26

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Essential Thrombocythemia; Extramedullary Plasmacytoma; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Noncontiguous Stage II Mantle Cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Stage 0 Chronic Lymphocytic Leukemia; Stage I Childhood Anaplastic Large Cell

  1. Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies

    ClinicalTrials.gov

    2016-01-05

    Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage I Small Lymphocytic Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood

  2. Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-05-27

    Treated Myelodysplastic Syndromes; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Primary Myelofibrosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Multiple Myeloma; Stage I Small Lymphocytic Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Lymphoblastic Lymphoma

  3. Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2015-06-30

    Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult Hepatocellular Carcinoma; Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult Solid Neoplasm; Adult T Acute Lymphoblastic Leukemia; Advanced Adult Hepatocellular Carcinoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Localized Non-Resectable Adult Liver Carcinoma; Localized Resectable Adult Liver Carcinoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Progressive Hairy Cell Leukemia Initial Treatment; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Liver Carcinoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Small Lymphocytic Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult

  4. Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction

    ClinicalTrials.gov

    2014-02-21

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage

  5. FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2014-01-06

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell

  6. Tanespimycin and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2014-02-21

    Adult Grade III Lymphomatoid Granulomatosis; AIDS-related Peripheral/Systemic Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous

  7. Genetic Testing Plus Irinotecan in Treating Patients With Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-01-23

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic

  8. Bevacizumab and Cediranib Maleate in Treating Patients With Metastatic or Unresectable Solid Tumor, Lymphoma, Intracranial Glioblastoma, Gliosarcoma or Anaplastic Astrocytoma

    ClinicalTrials.gov

    2014-02-14

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV

  9. PXD101 and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-05-15

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV

  10. 3-AP and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-09-27

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T

  11. PXD101 and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2013-05-01

    Adult Grade III Lymphomatoid Granulomatosis; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin

  12. AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma

    ClinicalTrials.gov

    2016-03-16

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large

  13. Follicular mucinosis - Case report*

    PubMed Central

    Passos, Paola C. Vieira da Rosa; Zuchi, Manuela Ferrasso; Fabre, Andréa Buosi; Martins, Luis Eduardo A. Machado

    2014-01-01

    Follicular mucinosis, also known as alopecia mucinosa, is a cutaneous mucinosis histologically characterized by accumulation of dermal type mucin in the pilosebaceous follicle and sebaceous glands. It presents in two forms, a primary or idiopathic form and a secondary form associated with various benign or malignant processes. Among the malignant processes, the main association is with mycosis fungoides. The frequent overlap of clinical, histopathological, immunohistochemical and molecular biology characteristics makes the correct classification of these conditions difficult, therefore a long follow-up of all cases is recommended. We report the case of an adolescent with disseminated lesions and discuss the difficulty of early identification of secondary follicular mucinosis associated with cutaneous lymphoma. PMID:24770517

  14. Panobinostat and Everolimus in Treating Patients With Recurrent Multiple Myeloma, Non-Hodgkin Lymphoma, or Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-04-19

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; Waldenström Macroglobulinemia

  15. Fusariosis occurring in an ulcerated cutaneous CD8+ T cell lymphoma tumor.

    PubMed

    Hsu, Chao-Kai; Hsu, Mark Ming-Long; Lee, Julia Yu-Yun

    2006-01-01

    Fusarium species have recently emerged as the second most common pathogenic mold in immunocompromised patients, and they are moderately resistant to most antifungal agents. The skin lesions of disseminated fusariosis typically manifest as multiple red or violaceous macules or nodules, often ulcerated and covered by a black eschar. We report a case of cutaneous fusariosis in a patient with long-standing hypopigmented mycosis fungoides. The infection was successfully treated with a 3-month course of oral voriconazole. The present case is unusual in that the infection occurred within a pre-existing, ulcerated lesion of cutaneous CD8+ lymphoma, resulting clinically in confusion with pyoderma gangrenosum and necrosis of lymphoma. A high index of suspicion will prompt a timely biopsy as well as isolation of the fungus, and early institution of systemic antifungal therapy. PMID:16709499

  16. Immunopathogenesis and therapy of cutaneous T cell lymphoma

    PubMed Central

    Kim, Ellen J.; Hess, Stephen; Richardson, Stephen K.; Newton, Sara; Showe, Louise C.; Benoit, Bernice M.; Ubriani, Ravi; Vittorio, Carmela C.; Junkins-Hopkins, Jacqueline M.; Wysocka, Maria; Rook, Alain H.

    2005-01-01

    Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of lymphoproliferative disorders caused by clonally derived, skin-invasive T cells. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of CTCLs and are characterized by malignant CD4+/CLA+/CCR4+ T cells that also lack the usual T cell surface markers CD7 and/or CD26. As MF/SS advances, the clonal dominance of the malignant cells results in the expression of predominantly Th2 cytokines, progressive immune dysregulation in patients, and further tumor cell growth. This review summarizes recent insights into the pathogenesis and immunobiology of MF/SS and how these have shaped current therapeutic approaches, in particular the growing emphasis on enhancement of host antitumor immune responses as the key to successful therapy. PMID:15841167

  17. Cutaneous T-Cell Lymphoma in Asians

    PubMed Central

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

    2012-01-01

    Cutaneous T-cell lymphoma describes a heterogeneous group of neoplasms of skin homing T cells that vary considerably in clinical presentation, histologic appearance, immunophenotype, and prognosis. This paper addresses the cutaneous T-cell lymphoma in Asians with respect to clinical-epidemiologic and histopathological features. Compared with Western countries, Asia usually has higher rates of cutaneous T-cell lymphomas such as extranodal NK/T-cell lymphoma, hydroa vacciniforme-like lymphoma, subcutaneous panniculitis T-cell lymphoma, and adult T-cell leukemia/lymphoma and lower rates of cutaneous B-cell lymphomas. Among many variants of mycosis fungoides, hypopigmented lesions, pityriasis lichenoides-like lesions, and ichthyosiform lesions are more prevalent in Asia than in the West. Adult T-cell leukemia/lymphoma is endemic in southwestern Japan especially in the Kyushu island. The clinicopathologic characteristics of cutaneous lymphoma vary according to geography, and this may be ascribed to genetic and environmental etiologic factors. PMID:22844610

  18. Pityriasis lichenoides chronica in black patients.

    PubMed

    Lane, Tanda N; Parker, Sareeta S

    2010-03-01

    Pityriasis lichenoides chronica (PLC) is a cutaneous disease of unknown etiology that most commonly affects children and young adults. The highly variable presentation of this condition often poses a diagnostic challenge. The clinical presentation of PLC in black patients is not well described. We report a series of 5 black patients (4 children and 1 young adult) with PLC who presented with extensive hypopigmentation and prominent facial involvement. One patient had concomitant mycosis fungoides (MF). The diagnosis of PLC should be included in the differential diagnosis in dark-skinned patients who present with widespread hypopigmented macules and patches. The presence of MF in one of our patients underscores the potential relationship between MF and PLC. PMID:20408509

  19. Cutaneous T-cell lymphoma in asians.

    PubMed

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

    2012-01-01

    Cutaneous T-cell lymphoma describes a heterogeneous group of neoplasms of skin homing T cells that vary considerably in clinical presentation, histologic appearance, immunophenotype, and prognosis. This paper addresses the cutaneous T-cell lymphoma in Asians with respect to clinical-epidemiologic and histopathological features. Compared with Western countries, Asia usually has higher rates of cutaneous T-cell lymphomas such as extranodal NK/T-cell lymphoma, hydroa vacciniforme-like lymphoma, subcutaneous panniculitis T-cell lymphoma, and adult T-cell leukemia/lymphoma and lower rates of cutaneous B-cell lymphomas. Among many variants of mycosis fungoides, hypopigmented lesions, pityriasis lichenoides-like lesions, and ichthyosiform lesions are more prevalent in Asia than in the West. Adult T-cell leukemia/lymphoma is endemic in southwestern Japan especially in the Kyushu island. The clinicopathologic characteristics of cutaneous lymphoma vary according to geography, and this may be ascribed to genetic and environmental etiologic factors. PMID:22844610

  20. A Case of Poikiloderma Vasculare Atrophicans

    PubMed Central

    Choi, Myoung-Soon; Lee, Jee-Bum; Kim, Seong-Jin; Lee, Seung-Chul; Won, Young-Ho

    2011-01-01

    Poikiloderma vasculare atrophicans (PVA) is a rare variant of mycosis fungoides, and is characterized by generalized hyperkeratotic scaly papules in net-like, retiform, or zebra-like patterns. A 59-year-old Korean woman presented with asymptomatic, erythematous-to-violaceous, reticulated confluent papules on the trunk and extremities. Skin lesions were initially limited to both thighs 25 years ago, and then spread slowly over her body. Histopathological examination showed band-like inflammatory infiltrations and epidermotropism consisting of mostly CD8+ lymphocytes. Based on the clinical manifestations and histological findings, the diagnosis of PVA was made. We herein report on a case of PVA, which featured a long-benign course without progression into the tumor stage over a period of 30 years. PMID:22028572

  1. Obatoclax Mesylate, Vincristine Sulfate, Doxorubicin Hydrochloride, and Dexrazoxane Hydrochloride in Treating Young Patients With Relapsed or Refractory Solid Tumors, Lymphoma, or Leukemia

    ClinicalTrials.gov

    2014-04-30

    Acute Leukemias of Ambiguous Lineage; Acute Undifferentiated Leukemia; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Small Intestine Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  2. Studies on porphyrin photoproducts in solution, cells, and tumor tissue

    NASA Astrophysics Data System (ADS)

    Koenig, Karsten; Schneckenburger, Herbert; Rueck, Angelika C.; Koenig, Roland

    1994-07-01

    Light excitation of photosensitizing porphyrins leads to cytotoxic reactions. In addition, photobleaching and photoproduct formation occur indicating photosensitizer destruction. Photoproducts from hematoporphyrin (HP) fluoresce in aqueous solution at 642 nm, whereas photoproducts from protoporphyrin (PP) in hydrophobic environment emit around 670 nm and exhibit pronounced absorption at 665 nm. Photoproduct formation depends on singlet oxygen. The photoproducts exhibit faster fluorescence decay kinetics compared with nonirradiated porphyrins, as shown by time-grated spectroscopy and fluorescence decay measurements. Photoproduct fluorescence was observed during light exposure of cells and of tumor-bearing, nude mice, following administration of Hematoporphyrin Derivative (HpD), tetramethyl-HP, and PP. Photoconversion was also detected with naturally-occurring porphyrins (PP-producing bacteria) and ALA-simulated biosynthesis of PP in tumor tissue and in skin lesions of patients (psoriasis, mycosis fungoides). The efficiency of PDT with porphyrin photoproducts was found to be low in spite of the strong electronic transitions in the red spectral region.

  3. Total-skin electron irradiation for cutaneous T-cell lymphoma: the Northern Israel Oncology Center experience.

    PubMed

    Kuten, A; Stein, M; Mandelzweig, Y; Tatcher, M; Yaacov, G; Epelbaum, R; Rosenblatt, E

    1991-07-01

    Total-skin electron irradiation (TSEI) is effective and frequently used in the treatment of cutaneous T-cell lymphoma. A treatment technique has been developed at our center, using the Philips SL 75/10 linear accelerator. In our method, the patient is irradiated in a recumbent position by five pairs of uncollimated electron beams at a source to skin distance of 150 cm. This method provides a practical solution to clinical requirements with respect to uniformity of electron dose and low X-ray contamination. Its implementation does not require special equipment or modification of the linear accelerator, 19 of 23 patients (83%) with mycosis fungoides, treated by this method, achieved complete regression of their cutaneous lesions. PMID:1858014

  4. Prolonged or Standard Infusion of Cefepime Hydrochloride in Treating Patients With Febrile Neutropenia

    ClinicalTrials.gov

    2013-07-10

    Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloid Leukemia; Adult Burkitt Lymphoma; Adult Diffuse Large Cell Lymphoma; Adult Diffuse Mixed Cell Lymphoma; Adult Diffuse Small Cleaved Cell Lymphoma; Adult Hodgkin Lymphoma; Adult Immunoblastic Large Cell Lymphoma; Adult Lymphoblastic Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Breast Cancer; Chronic Eosinophilic Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Cutaneous T-cell Non-Hodgkin Lymphoma; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Malignant Testicular Germ Cell Tumor; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Multiple Myeloma; Mycosis Fungoides/Sezary Syndrome; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neutropenia; Nodal Marginal Zone B-cell Lymphoma; Ovarian Epithelial Cancer; Ovarian Germ Cell Tumor; Plasma Cell Neoplasm; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Primary Myelofibrosis; Prolymphocytic Leukemia; Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma

  5. Cutaneous T-Cell Lymphoma: A Review with a Focus on Targeted Agents.

    PubMed

    Devata, Sumana; Wilcox, Ryan A

    2016-06-01

    Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of extranodal lymphomas involving the skin. Diagnosis of the two main subtypes of CTCL-mycosis fungoides (MF) and Sézary syndrome (SS)-is based on the International Society for Cutaneous Lymphomas/European Organization for Research and Treatment of Cancer (ISCL/EORTC) classification system, which utilizes clinical, histopathological, molecular biologic, and immunopathologic features. Risk stratification, based on TNMB (tumor, node, metastasis, and blood) staging, provides prognostic information, with limited-stage disease conferring the longest median overall survival. Skin-directed therapies are preferred in the management of limited-stage disease, whereas advanced-stage disease requires systemic therapies. As the mechanisms of CTCL pathogenesis are increasingly understood, new monoclonal antibodies, checkpoint inhibitors, immunomodulatory agents, and small molecules are under investigation and may provide additional therapeutic options for those with advanced CTCL. This review examines the current landscape of targeted therapies in the treatment of CTCLs. PMID:26923912

  6. Poikiloderma Vasculare Atrophicans: A Distinct Clinical Entity?

    PubMed Central

    Mahajan, Vikram K; Chauhan, Pushpinder S; Mehta, Karaninder S; Sharma, Anju Lath

    2015-01-01

    This paper describes a typical case of poikiloderma vasculare atrophicans (PVA) in a 48-year-old female. Histologically, the features were suggestive of PVA with the absence of Pautrier's microabscess or atypical lymphoid cells. The biopsy specimen was positive for cluster of differentiation (CD) 8 on immunohistochemical staining. Its exact pathogenesis remains obscure, and it remains unclear whether PVA actually is mycosis fungoides (MF), a forme fruste of MF, or a distinct and benign dermatosis with CD8+ phenotype that can perhaps be labeled as PVA. However, it has a long benign clinical course without progression to tumor stage of MF in most cases, and its status within the spectrum of cutaneous T-cell lymphoma remains poorly understood. Yet it is imperative to distinguish PVA from poikilodermic MF. PMID:25814753

  7. CPI-613, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-07-26

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  8. Oxaliplatin, Ifosfamide and Etoposide in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2014-02-21

    Angioimmunoblastic T-cell Lymphoma; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  9. Bendamustine Hydrochloride, Etoposide, Dexamethasone, and Filgrastim For Peripheral Blood Stem Cell Mobilization in Treating Patients With Refractory or Recurrent Lymphoma or Multiple Myeloma

    ClinicalTrials.gov

    2016-03-08

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  10. Resident memory T cells in human health and disease

    PubMed Central

    Clark, Rachael A.

    2015-01-01

    Resident memory T cells are non-recirculating memory T cells that persist long term in epithelial barrier tissues, including the gastrointestinal tract, lung, skin and reproductive tract. Resident memory T cells persist in the absence of antigens, have impressive effector functions and provide rapid on-site immune protection against known pathogens in peripheral tissues. A fundamentally distinct gene expression program differentiates resident memory T cells from circulating T cells. Although these cells likely evolved to provide rapid immune protection against pathogens, autoreactive, aberrantly activated and malignant resident memory cells contribute to numerous human inflammatory diseases including mycosis fungoides and psoriasis. This review will discuss both the science and medicine of resident memory T cells, exploring how these cells contribute to healthy immune function and discussing what is known about how these cells contribute to human inflammatory and autoimmune diseases. PMID:25568072

  11. [Skin memory: the clinical implications].

    PubMed

    Gaide, Olivier

    2016-03-30

    Activated T lymphocytes give rise to daughter cells that can persist for decades in our body, while retaining their ability to provide a strong immune response. Recent advances have highlighted the fact that a significant portion of these memory cells are found directly in peripheral tissues and lack the capacity to migrate to the blood. We have recently shown that these cells, called Tissue Resident Memory T cells (T(RM)), play a major role in the immune response, regardless of the antigenic challenge. They have a backup of circulating central memory T cells (T(CM)) that bear the exact same T cell receptor. For the clinician, this knowledge is very useful as it allows a better understanding and better choice of therapeutics for several cutaneous diseases, such as contact dermatitis and cutaneous T cell lymphoma (Mycosis Fungoides vs Sezary). PMID:27172692

  12. Rituximab in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

    ClinicalTrials.gov

    2014-05-28

    Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage I Small Lymphocytic Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone

  13. Adult T-cell leukemia-lymphoma associated with follicular mucinosis.

    PubMed

    Ballester, Leomar Y; Cowen, Edward W; Lee, Chyi-Chia Richard

    2014-11-01

    Follicular mucinosis is frequently associated with follicular mycosis fungoides, but its association with adult T-cell leukemia-lymphoma (ATLL) is extremely rare. We report a case of a 50-year-old female patient with a history of ATLL, after multiple treatments, with residual/recurrent skin tumors in the forehead and legs. Biopsy of a skin tumor from the forehead revealed a perifollicular and intrafollicular atypical lymphoid infiltrate with abundant mucin deposition. Immunohistochemical stains showed that the atypical cells were positive for CD3, CD4, and CD25. Reverse transcription polymerase chain reaction performed on the tissue sections confirmed the presence of human T-cell leukemia virus in the biopsies of skin tumors. To our knowledge, this is only the third reported case of a follicular mucinosis in the setting of ATLL. PMID:24614206

  14. 308nm excimer laser in dermatology.

    PubMed

    Mehraban, Shadi; Feily, Amir

    2014-01-01

    308nm xenon-chloride excimer laser, a novel mode of phototherapy, is an ultraviolet B radiation system consisting of a noble gas and halide. The aim of this systematic review was to investigate the literature and summarize all the experiments, clinical trials and case reports on 308-nm excimer laser in dermatological disorders. 308-nm excimer laser has currently a verified efficacy in treating skin conditions such as vitiligo, psoriasis, atopic dermatitis, alopecia areata, allergic rhinitis, folliculitis, granuloma annulare, lichen planus, mycosis fungoides, palmoplantar pustulosis, pityriasis alba, CD30+ lympho proliferative disorder, leukoderma, prurigo nodularis, localized scleroderma and genital lichen sclerosus. Although the 308-nm excimer laser appears to act as a promising treatment modality in dermatology, further large-scale studies should be undertaken in order to fully affirm its safety profile considering the potential risk, however minimal, of malignancy, it may impose. PMID:25606333

  15. Lymphoma in acquired generalized lipodystrophy.

    PubMed

    Brown, Rebecca J; Chan, Jean L; Jaffe, Elaine S; Cochran, Elaine; DePaoli, Alex M; Gautier, Jean-Francois; Goujard, Cecile; Vigouroux, Corinne; Gorden, Phillip

    2016-01-01

    Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression. PMID:25864863

  16. SU-E-T-193: FMEA Severity Scores - Do We Really Know?

    SciTech Connect

    Khan, A; Robertson, JD; Narra, V; Yue, N; Howell, R

    2014-06-01

    Purpose: Mycosis fungoides is a common form of cutaneous T-cell lymphoma which generally affects the skin. A typical course of treatment may include fractionated total skin electron beam therapy. Given the difficulties in uniformly irradiating some regions of the body and the need for frequent visits within the context of a fractionated protocol, this study investigated the feasibility of delivering the dose using form-fitting cloth which contained phosphorous-32 as a source for beta particle irradiation. Methods: A piece of fabric (0.97 g) consisting of a blend of spandex and flame retardant material impregnated with phosphorus-31 (2000 ppm) was bombarded with neutrons to produce phosphorus-32. The cloth was then laid flat and a stack of radiochromic film placed on top. Sheets of film and tissue equivalent plastic were layered to form a stack measuring a total of 1 cm thickness and remained sandwiched for 77.3 hr. Results: The initial activity of the activated cloth was 44 μCi of P-32. The absorbed dose was uniform within planes parallel to the cloth and exponentially dependent on depth, delivering 560cGy at 0.3mm and falling to 20cGy at 3mm. Conclusion: The total dose prescribed for a typical course of TSET for mycosis fungoides is 36Gy delivered over 9 weeks and is expected to treat to at least 5mm depth. Therefore, the P-32 impregnated cloth may not be clinically indicated to treat this disease given the unfavorable depth-dose characteristics. However, a major advantage of using form-fitting cloth is the uniformity with which the dose could be delivered over the skin in areas which are not flat. Increasing the distance between cloth and skin could improve the depth-dose characteristics.

  17. Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer

    ClinicalTrials.gov

    2015-08-28

    ; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage I Small Lymphocytic Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Hodgkin Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Childhood Small Noncleaved Cell Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage III Childhood Small Noncleaved Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III

  18. 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

    ClinicalTrials.gov

    2013-02-06

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Chondrosarcoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Nodal Marginal Zone B-cell Lymphoma; Ovarian Sarcoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Osteosarcoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Uterine Sarcoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small

  19. MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2013-01-23

    Adult Grade III Lymphomatoid Granulomatosis; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  20. A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites.

    PubMed Central

    Picker, L. J.; Michie, S. A.; Rott, L. S.; Butcher, E. C.

    1990-01-01

    It has been proposed that the skin is a functionally unique compartment of the immune system, although little direct evidence supporting this hypothesis has been presented. Here we show that lymphocyte populations at cutaneous sites can be differentiated from otherwise similar populations at noncutaneous sites by their preferential expression of an epitope defined by the MAb HECA-452. This MAb recognizes a predominantly 200-kd cell-surface glycoprotein present on about 16% of peripheral blood T cells, including both CD4+ and CD8+ T cells (17% and 11% HECA-452+, respectively), as well as TCR-delta-bearing T cells (32%+). Most thymocytes (99%) lacked HECA-452 antigen expression, and essentially all the HECA-452+ peripheral blood T cells were found in the adhesion molecule high, CD45R low putative memory cell subset, findings suggesting that HECA-452 expression develops peripherally as a consequence of antigenic stimulation. However, the HECA-452 antigen is not a conventional activation antigen because it was not upregulated with mitogen stimulation of peripheral blood T cells. Most significantly, among 54 diverse specimens of normal/reactive lymphoid tissues and sites of chronic inflammation, there was a clear association of lymphocyte HECA-452 expression and cutaneous location. In extracutaneous sites (n = 38) only about 5% of lymphocytes within the T-cell areas of these tissues expressed this antigen, whereas in inflammatory skin lesions (n = 16), 85% were HECA-452+. The association of HECA-452 expression and cutaneous location was also seen in a series of T-cell lymphomas. The malignant cells of 16 of 18 cases of epidermotropic (patch/plaque) stage mycosis fungoides were HECA-452+, as well as 2 of 7 nonmycosis fungoides peripheral T-cell lymphomas in skin. In contrast, this antigen was not expressed in thymic (lymphoblastic) lymphomas (n = 14), nonepidermotropic (tumor) stage mycosis fungoides (n = 5), and noncutaneous peripheral T-cell lymphomas (n = 15). Among

  1. A favorable clinical effect of an expectorant in allergic bronchopulmonary mycosis caused by Schizophyllum commune.

    PubMed

    Kobayashi, Haruki; Taira, Tetsuhiko; Wakuda, Kazushige; Takahashi, Toshiaki; Endo, Masahiro

    2016-01-01

    An 80-year-old Japanese woman with wet cough and dyspnea was diagnosed with pneumonia at a clinic. Antibiotics did not improve her symptoms; therefore, she was referred to our hospital one month after symptom onset. Chest radiograph findings revealed complete collapse of the left lung. Bronchoscopy showed white mucus plug in the left main bronchus, which could not be removed. She was initially treated with bromhexine. Subsequently, culture results of the mucus plug specimen obtained during bronchoscopy yielded Schizophyllum commune. After three weeks, improvement of the collapsed lung was observed on chest radiograph. PMID:27489762

  2. Cutaneous mycosis in a Barbastelle bat (Barbastella barbastellus) caused by Hyphopichia burtonii.

    PubMed

    Simpson, Victor R; Borman, Andrew M; Fox, Richard I; Mathews, Fiona

    2013-07-01

    A rare barbastelle bat (Barbastella barbastellus) died shortly after being found in emaciated condition in Devon, England. The skin over the muzzle and face was grossly thickened, crusty, and in places was sloughing and ulcerated. There were numerous nodules up to 3 mm in diameter on both wings and ear pinnae. Histologically, multiple foci of epidermal hyperplasia, hyperkeratosis, and crateriform erosions containing masses of fungal spores and septate hyphae were found in the wing. Epidermal hyperplasia and follicular hyperkeratosis, with fungal masses within keratinized follicles and also in fissured stratum corneum, were found in the pinna. Hyphae did not invade the dermis, and there was no inflammation, but there was multifocal serous exudation and crusting. No parasites or other significant organisms were identified. Microscopic and multiple cultural analyses of face and wing lesions demonstrated (10/10) a fine, septate fungus bearing laterally oval to clavate conidia; morphologically and culturally this was entirely consistent with Hyphopichia burtonii, and polymerase chain reaction analysis and sequencing gave 100% identity with the type strain. The organism isolated was morphologically consistent with that repeatedly seen in histology sections and demonstrates that although H. burtonii has not previously been recognized as a dermatophyte, it clearly has the ability to invade the skin of live bats. Although not identical, the lesions in this case show similarity with those of white nose syndrome and therefore H. burtonii should be considered as a potential pathogen of bats. PMID:23794016

  3. Mycotic encephalitis, sinus osteomyelitis, and guttural pouch mycosis in a 3-year-old Arabian colt.

    PubMed

    Hunter, Barbara; Nation, Patrick N

    2011-12-01

    Mycotic encephalitis caused severe ataxia and other neurologic deficits in a horse. The finding of a single, large focus of cerebral malacia, with histopathologic evidence of fungal elements, suggested infection was a result of direct transfer from the frontal sinuses, rather than hematogenous spread from the guttural pouch. PMID:22654140

  4. Tracheobronchial Mycosis in a Retrospective Case-Series Study of Five Status Asthmaticus Patients

    PubMed Central

    Mak, Garbo; Porter, Paul C.; Bandi, Venkata; Kheradmand, Farrah; Corry, David B.

    2013-01-01

    The aetiology of status asthmaticus (SA), a complication of severe asthma, is unknown. Fungal exposure, as measured by fungal atopy, is a major risk factor for developing asthma, but the relationship of fungi in SA per se has not previously been reported. In this five patient retrospective case series study, lower respiratory tract cultures were performed on bronchoalveolar lavage or tracheal aspirate fluid, comparing standard clinical laboratory cultures with a specialized technique in which respiratory mucus was removed prior to culture. We show mucolytic treatment allows increased detection of fungal growth, especially yeast, from the lower airways of all SA patients. We also demonstrate that the yeast Candida albicans inhalation readily induces asthma-like disease in mice. Our observations suggest, SA may represent a fungal infectious process, and supports additional prospective studies utilizing anti-fungal therapy to supplement conventional therapy, broad-spectrum antibiotics and high-dose glucocorticoids, which can promote fungal overgrowth. PMID:23280490

  5. Mycosis Inhibits Cannibalism by Melanoplus sanguinipes, M. differentialis, Schistocerca americana, and Anabrus simplex

    PubMed Central

    Jaronski, Stefan T.

    2013-01-01

    Cannibalism is common among the Acrididae and the Mormon cricket, Anabrus simplex Haldeman (Orthoptera: Tettigoniidae). This behavior has been proposed as a mechanism for the horizontal transmission of Microsporida and entomopathogenic fungi. Aanecdotal observations suggested that the migratory grasshopper, Melanoplus sanguinipes Fabricius (Acrididae), and A. simplex did not eat cadavers that had been killed by insect pathogenic fungi. The hypothesis tested was that A. simplex or M. sanguinipes would not cannibalize individuals freshly killed by the entomopathogenic fungi, Beauveria bassiana Bals.-Criv. (Vuill.) (Hypocreales: Clavicipitaceae), or Metarhizium acridum (Driver and Milner) Bischoff, Rehner, and Humber. Cannibalism was examined in a series of no-choice tests with individual insects. Test insects included healthy adults of M. sanguinipes; the differential grasshopper, M. differentialis (Thomas); the American grasshopper, Schistocerca americana (Drury) (Acrididae); and A. simplex. Individual, starved Acrididae or A. simplex were confined in small cages with either a fungus-killed (but unsporulated) or uninfected cadaver. The insects were then observed periodically for the first 4 hr. After 24 hr, the cadavers were scored for the degree to which they had been consumed. Very few mycotic cadavers were fed upon by the healthy insects, and, at most only the tarsi were eaten. All four species generally refused to eat fungus-infected cadavers. In contrast, freeze-killed cadavers were partly or entirely consumed by most of the test insects, often within a few hours. Transmission of infection through contact in these tests was between 0–18.9%, depending upon the fungus and insect species, and was lower than the prevalence of cannibalism in all cases. PMID:24786183

  6. [Epidemiological transition of mycosis diseases in sub-Saharan Africa: from surface to depth].

    PubMed

    Chandenier, J; Desoubeaux, G

    2015-02-01

    Fungi are schematically responsible for three distinct kinds of infections: superficial mycoses, subcutaneous and deep ones. The current socio-epidemiological transition observed in sub-Saharan Africa does not actually lead to similar consequences regarding these three categories of fungal entities. For instance, it has long been known that superficial mycoses are very prevalent in tropical areas, since they are partly due to the warm climate and the promiscuity. They are mostly caused by dermatophytic fungi or Malassezia sp. (Pityriasis versicolor). Subcutaneous mycoses are rarer, and usually due to dimorphic fungi which are accidentally inoculated into the body after a skin injury or a trauma. Sometimes very spectacular, the clinical outcome is then described as chronic. Thus, chromoblastomycosis, rhinoentomophtoromycosis or mycetoma are some examples of subcutaneous mycoses which remain well-known by practitioners of endemic countries. Deep mycoses (or invasive / systemic mycoses) are defined by fungal infections of deep anatomical sites that should be normally sterile. By contrast with the other entities mentioned above, the outcome may be rapidly fatal for the patient. One of the most outstanding examples was the great increasing of cryptococcal meningitis during the HIV outbreak in the 80'. A few other similar mycoses may be feared in a near future, since they usually occur in contexts of important immunosuppression which are about to be definitely experienced in Africa: overall increase of chronic diseases like diabetes, lengthening life expectancy and its associated diseases, widespread medical practices which were only seen in advanced intensive care units, onco-haematology departments or graft centers so far. Thus, the deep mycoses will inevitably increase in Africa, as they did in all developed countries over the last two decades. The consequences will not only be limited to the clinical management as described above: the diagnostic approach is also quite particular, since the identification of the involved fungal species should be established in emergency, if not the outcome will be fatal. Besides, the antifungal drugs are expensive, and their therapeutic monitoring is quite challenging all along the follow up. Overall, we have to thoroughly take into account the emergence of invasive mycoses right now in Intertropical Africa, in order to successfully achieve the socio-economic development of this continent. PMID:24997574

  7. Mycosis inhibits cannibalism by Melanoplus sanguinipes, M. differentialis, Schistocerca americana, and Anabrus simplex

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cannibalism is common among the Acrididae and the Mormon cricket, Anabrus simplex, a tettigonid. These behaviors have been proposed as mechanisms for the horizontal transmission of Microsporida and entomopathogenic fungi. After anecdotal observations that Melanoplus sanguinipes and A. simplex did ...

  8. Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant

    ClinicalTrials.gov

    2015-06-03

    ; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult

  9. Deferasirox in Treating Iron Overload Caused By Blood Transfusions in Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2014-12-09

    ; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Anemia; Refractory Multiple Myeloma; Secondary Acute Myeloid Leukemia; Secondary Myelofibrosis; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage I Mycosis Fungoides/Sezary Syndrome

  10. Fludarabine Phosphate, Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, Total-Body Irradiation, and Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancer

    ClinicalTrials.gov

    2014-02-27

    ; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  11. RO4929097 and Capecitabine in Treating Patients With Refractory Solid Tumors

    ClinicalTrials.gov

    2014-11-06

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; HER2-negative Breast Cancer; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Male Breast Cancer; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Rectal Cancer; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic

  12. Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction

    ClinicalTrials.gov

    2013-02-06

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Gastrointestinal Stromal Tumor; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Meningeal Chronic Myelogenous Leukemia; Monoclonal Gammopathy of Undetermined Significance; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Central Nervous System Non-Hodgkin Lymphoma; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory

  13. The treatment of extensive scalp lesions using coplanar and non-coplanar photon IMRT: a single institution experience

    PubMed Central

    2014-01-01

    Background This clinical study compared four different cases of extensive scalp malignancies treated by intensity-modulated radiation therapy. The merits of coplanar and non-coplanar Step-and-shoot total scalp irradiation techniques were evaluated against the background of the literature. Methods Four patients (angiosarcoma, n=2, cutaneous B-cell non-Hodgkin lymphoma, B-NHL, n=1, mycosis fungoides, n=1) treated between 2008 and 2012 at our institution were retrospectively analyzed. For every patient with executed coplanar plan, a non-coplanar plan and vice versa has been calculated additionally for direct comparison. Three patients underwent limited surgery before radiotherapy. Individual adapted bolus material was used for every patient (helmet). Total scalp dose was 30 Gy (B-NHL, mycosis fungoides) and 50 Gy (angiosarcoma) with fractional doses of 2.0-2.5 Gy (without sequential local boost in three patients). Conformity and homogeneity indexes and dose volume histograms were used for treatment plan comparison. Results Dose hot spots were higher in coplanar plans (110-128% Dmax). Non-coplanar plans showed a more homogeneous dose distribution (HI = .12 - .17) and superior PTV coverage (88 - 96%). Target dose coverage was 81-117% in non-coplanar and 30-128% in coplanar plans. Coplanar plans yielded a stronger dose gradient across the target (.7-1.6 Gy/mm) compared to non-coplanar plans (.8-1.3 Gy/mm). The most conformal plan was a non-coplanar plan (CI = .7). Mean and maximum brain doses were comparable and showed an almost linear decrease between min. and max. dose. The optic chiasm and brain stem was spared most with non-coplanar plans, mean doses to the lenses ranged between 4 and 8 Gy and were higher in non-coplanar plans as were doses to the optic nerves. Radiotherapy tolerance was acceptable and acute side effects included erythema, scalp pain, alopecia and radiodermatitis which all spontaneously resolved. Two patients accomplished partial response, two

  14. C-type lectin receptors differentially induce th17 cells and vaccine immunity to the endemic mycosis of North America.

    PubMed

    Wang, Huafeng; LeBert, Vanessa; Hung, Chiung Yu; Galles, Kevin; Saijo, Shinobu; Lin, Xin; Cole, Garry T; Klein, Bruce S; Wüthrich, Marcel

    2014-02-01

    Vaccine immunity to the endemic mycoses of North America requires Th17 cells, but the pattern recognition receptors and signaling pathways that drive these protective responses have not been defined. We show that C-type lectin receptors exert divergent contributions to the development of antifungal Th17 cells and vaccine resistance against Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides posadasii. Acquired immunity to B. dermatitidis requires Dectin-2, whereas vaccination against H. capsulatum and C. posadasii infection depends on innate sensing by Dectin-1 and Dectin-2, but not Mincle. Tracking Ag-specific T cells in vivo established that the Card9 signaling pathway acts indispensably and exclusively on differentiation of Th17 cells, while leaving intact their activation, proliferation, survival, and migration. Whereas Card9 signaling is essential, C-type lectin receptors offer distinct and divergent contributions to vaccine immunity against these endemic fungal pathogens. Our work provides new insight into innate immune mechanisms that drive vaccine immunity and Th17 cells. PMID:24391211

  15. Laboratory mortality and mycosis of adult Curculio caryae (Coleoptera: Curculionidae) following application of Metarhizium anisopliae in the laboratory and field

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pecan weevil, Curculio caryae, is a key pest of pecans. Our objective was to determine the potential of Metarhizium anisopliae to control emerging C. caryae adults. First, a laboratory test was conducted to compare four Beauveria bassiana strains (Bb GA2, BbLA3, BbMS1, and GHA) and three M. an...

  16. Dermatitis and systemic mycosis in lined seahorses Hippocampus erectus associated with a marine-adapted Fusarium solani species complex pathogen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During a 4 month epizootic, 100% of 152 lined seahorses Hippocampus erectus in three separate groups died while in quarantine following shipment to a public aquarium. Twelve animals with skin depigmentation and ulceration were received by the Aquatic Pathology Service, University of Georgia, College...

  17. Factors influencing the sporulation and cyst formation of Aphanomyces invadans, etiological agent of ulcerative mycosis in Atlantic menhaden, Brevoortia tyrannus

    USGS Publications Warehouse

    Kiryu, Y.; Blazer, V.S.; Vogelbein, W.K.; Kator, H.; Shields, J.D.

    2005-01-01

    Oomycete infections caused by Aphanomyces invadans occur in freshwater and estuarine fishes around the world. Along the east coast of the USA, skin ulcers caused by A. invadans are prevalent in Atlantic menhaden, Brevoortia tyrannus. From laboratory observations low salinities appear crucial to transmission of the pathogen. To better understand aspects of transmission, we characterized sporulation and cyst formation of secondary zoospores of two isolates of A. invadans at different salinities and temperatures. Sporulation occurred only at low salinities. At room temperature (ca. 20-22 C), using "pond water" augmented with artificial sea salts, the endemic strain WIC and the Thailand strain PA7 of A. invadans produced free-swimming secondary zoospores at salinities of 0, 1 and 2 psu (practical salinity unit = ???), but not at 4 psu or higher. Secondary zoospores of another species, ATCC-62427 (Aphanomyces sp.), were observed at 1, 2, 4 and 8 psu but not at 0 and 12 psu. Secondary zoospores of all three isolates, especially WIC, were abundant and motile 1-2 d post-sporulation. Sporulation was temperature dependent and occurred over a relatively narrow range. No sporulation occurred at 4, 30 or 35 C for either WIC or PA7. For both strains zoospore production within 1-3 d after the initiation of sporulation was more prolific at 25 C than at 20 and 15 C. At 15 C production of zoospores was sustained over 11 d for WIC and 5 d for PA7. At room temperature single WIC secondary zoospores remained motile 12-18 h. Salinities exceeding 4 psu or vigorous shaking caused immediate cyst formation of WIC secondary zoospores. Exposure to menhaden tissue, but not tissues of other fishes to secondary zoospores (WIC), caused rapid (2 h) cyst formation. Cysts were capable of excysting when transferred to 1 psu water within 2-3 h of cyst formation. Cysts that had remained encysted in 6.5 psu for 24 h did not excyst when transferred to 1 psu water. Salinity and temperature requirements for sporulation indicate that juvenile menhaden must acquire infections during rain or in low salinity oligohaline waters. ?? 2005 by The Mycological Society of America.

  18. Invasive pulmonary mycosis due to Chaetomium globosum with false-positive galactomannan test: a case report and literature review.

    PubMed

    Capoor, Malini R; Agarwal, Poojan; Goel, Manoj; Jain, Sarika; Shivaprakash, Mandya Rudramurthy; Honnavar, Prasanna; Gupta, Sunita; Chakrabarti, Arunaloke

    2016-03-01

    In this case, the authors report Chaetomium globosum as a cause of invasive pulmonary infection in a patient with Wegener's granulomatosis. Fungal hyphae (KOH and Calcofluor) were seen on direct microscopy of lung biopsy sample and bronchoalveolar lavage (BAL) sample. C. globosum isolated on culture clinched the diagnosis of invasive pulmonary infection by Chaetomium spp. A positive galactomannan of serum and BAL was repeatedly seen and was utilised for follow-up and as prognostic marker in patient management. The patient was successfully treated with liposomal amphotericin B followed by voriconazole. All the Chaetomium infections reported till date since 1980 are reviewed. Chaetomium spp. with its unique ecology has a hidden clinical potential to cause invasive mould infections. PMID:26691935

  19. Poikiloderma Vasculare Atrophicans Showing Features of Ashy Dermatosis in the Beginning

    PubMed Central

    Jeon, Jiehyun; Kim, Joo Ha; Ahn, Jae Woo

    2015-01-01

    Poikiloderma vasculare atrophicans (PVA) is a rare poikilodermatous variant of early-stage mycosis fungoides characterized by generalized poikiloderma, atrophy, mottled dyspigmentation, and telangiectasia. In 2001, a 14-year-old male presented with asymptomatic brownish-gray polymorphic macules throughout the body with flexural accentuation. A skin biopsy showed increased melanophages with focal hydropic changes. Ashy dermatosis was considered a possible diagnosis. In 2005, the lesions began to show darkening and lichenification in the lower part of the trunk. In 2011, his skin showed definite poikilodermatous changes, and a biopsy showed band-like inflammatory infiltrations of atypical lymphocytes, epidermal atrophy, and epidermotropism of predominantly CD4-CD8+ atypical T cells. In addition, results of T-cell receptor gene rearrangement analysis were positive. Based on the aforementioned findings, he was diagnosed with PVA. If a patient shows long-standing and progressive hyperpigmentary skin changes, periodic follow-up and repeated skin biopsies are recommended to determine the underlying condition. PMID:25834361

  20. Characteristics of Primary Cutaneous T-Cell Lymphoma in Iran: A 10-Year Retrospective Study

    PubMed Central

    Fatemi Naeini, Farahnaz; Sadeghiyan, Hamidreza; Pourazizi, Mohsen; Najafian, Jamshid; Abtahi-Naeini, Bahareh

    2014-01-01

    Background. Primary cutaneous T-cell lymphomas (CTCLs) are a group of extranodal non-Hodgkin lymphomas that may be present in the skin without any evidence of extracutaneous disease. The aim of this study was to evaluate the epidemiological characteristics of primary CTCL in Isfahan, Iran. Method. A total of 95 patients who were diagnosed as having primary CTCL were recruited during a 10-year period (2003–2013) and were classified according to the new WHO-EORTC criteria. Results. The patient group consisted of 43 (44.8%) males and 53 (55.2%) females, which indicated a female predominance (M : F ratio 1 : 1.2). The mean age at the time of diagnosis was 41.78 ± 16.88 years (range: 7–84 years). Prior to diagnosis, the lesions had persisted for a mean of 8.34 ± 4.38 years (range: 0–55 years). The age at peak diagnosis was 20–40 years (43%). The most frequent subtypes were mycosis fungoides (MF) (88.5%). Four patients died from CTCL-related complications. Conclusions. The distinguishing epidemiologic characteristics of primary CTCL, particularly those MF, in Iran, are the absence of a male predominance and lower age at diagnosis. This is likely because of the characteristic ethnic group diversity and increased susceptibility among younger population.