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Sample records for mycosis fungoides bullosa

  1. Defining early mycosis fungoides.

    PubMed

    Pimpinelli, Nicola; Olsen, Elise A; Santucci, Marco; Vonderheid, Eric; Haeffner, Andreas C; Stevens, Seth; Burg, Guenter; Cerroni, Lorenzo; Dreno, Brigitte; Glusac, Earl; Guitart, Joan; Heald, Peter W; Kempf, Werner; Knobler, Robert; Lessin, Stuart; Sander, Christian; Smoller, Bruce S; Telang, Gladys; Whittaker, Sean; Iwatsuki, Keiji; Obitz, Erik; Takigawa, Masahiro; Turner, Maria L; Wood, Gary S

    2005-12-01

    This editorial review summarizes the results of 5 meetings sponsored by the International Society for Cutaneous Lymphoma at which the clinicopathologic and ancillary features of early mycosis fungoides were critically examined. Based on this analysis, an algorithm was developed for the diagnosis of early mycosis fungoides involving a holistic integration of clinical, histopathologic, immunopathologic, and molecular biological characteristics. A novel aspect of this algorithm is that it relies on multiple types of criteria rather than just one, for example, histopathology. Before its finalization, the proposed diagnostic algorithm will require validation and possibly further refinement at multiple centers during the next several years. It is anticipated that a more standardized approach to the diagnosis of early mycosis fungoides will have a beneficial impact on the epidemiology, prognostication, treatment, and analysis of clinical trials pertaining to this most common type of cutaneous lymphoma.

  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.

  3. 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

  4. 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 ...

  5. Tumor Stage Mycosis Fungoides in a Child.

    PubMed

    Dulmage, Brittany O'Neill; Villaseñor-Park, Jennifer; Ho, Jonhan; Geskin, Larisa J; Grandinetti, Lisa M

    2015-01-01

    Mycosis fungoides is uncommon in children and most often presents as stage IA/IB. We present a case of stage IIB mycosis fungoides in a 13-year-old boy and discuss diagnostic examination and treatment considerations.

  6. Imiquimod in mycosis fungoides.

    PubMed

    Martínez-González, M Covadonga; Verea-Hernando, M Magdalena; Yebra-Pimentel, M Teresa; Del Pozo, Jesús; Mazaira, Marta; Fonseca, Eduardo

    2008-01-01

    Imiquimod is a topically active imidazoquinoline immunomodulator agent. It works as an indirect antiviral and antitumoral and stimulates the production of INF-alpha and various other cytokines. We assayed topical imiquimod in treating early stages of mycosis fungoides. We applied imiquimod 5% cream in four patients with multi-treatment resistant plaques of MF (stages IA and IIB). We applied it on one patient in association with systemic INFalpha-2a. We observed a complete clinical clearance of the lesions in all four patients. In three cases we achieved a complete histopathological clearance and in one case a partial histopathological clearance. The patient treated with imiquimod and systemic INFalpha-2a showed the most spectacular improvement with a rapid total response. We ascribe this improvement to a synergic effect of imiquimod and systemic INFalpha-2a treatment. Before the introduction of imiquimod, this patient had been treated for 2 years with systemic INFalpha-2a alone, without any evidence of clinical response. Imiquimod could be an effective therapy for early-stage disease of CTCL, used alone or in combination with systemic immunomodulatory therapy.

  7. Verrucous presentation in patients with mycosis fungoides.

    PubMed

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

    2016-03-01

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

  8. Verrucous presentation in patients with mycosis fungoides.

    PubMed

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

    2016-03-01

    Mycosis fungoides is a potentially fatal skin condition whose variable clinical appearance may mimic a variety of benign, inflammatory dermatoses, making it a diagnostic challenge. Three patients with mycosis fungoides, treated with multiple approved topical and systemic therapies, presented with acquired verrucous lesions on the extremities. The verrucous presentation of mycosis fungoides is one of the many atypical forms of the disease, with a paucity of documented cases in the medical literature. Although rare, verrucous and hyperkeratotic lesions in mycosis fungoides may increase the risk of considerable diagnostic delay if clinicians do not maintain a high degree of suspicion in cases of acquired verrucous lesions in the appropriate clinical setting. PMID:26519087

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

    ClinicalTrials.gov

    2016-07-29

    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

  10. Koebner Phenomenon and Mycosis Fungoides.

    PubMed

    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

  11. 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

  12. Systemic involvement in mycosis fungoides.

    PubMed

    Burg, Günter

    2015-01-01

    Mycosis fungoides (MF) represents almost 50% of all primary cutaneous lymphomas and more than 70% of cutaneous T-cell lymphomas (CTCL). Arising from preferentially skin-homing lymphocytes with genetic instability, MF evolves through stages (IA-IVB), producing inconspicuous inflammatory features in the beginning and finally resulting in a proliferation of cytomorphologic, phenotypic, and genotypic abnormal tumor cells. Over the past 200 years, there has been much confusion in the classification of lymphomas due to semantic disagreements (MF, CTCL, parapsoriasis, lymphosarcoma, reticulum cell sarcoma, and many other terms), lack of diagnostic standard criteria, and new molecular diagnostic methods. Studies on extracutaneous involvement in early stages (IA-IIA) are almost completely lacking. In advanced stages of MF (IIB-IVB), discovery of extracutaneous involvement is dependent on the methods used (physical examination, technology, molecular diagnostics, autopsy, and laparoscopy) and reveals a wide range of results. Due to the inflammation-simulating features in the beginning of the disease, early diagnosis is very difficult to assess. Extracutaneous involvement has previously been documented in more than 70% of autopsies. More recent studies give much lower figures. Like all lymphomas, MF is a systemic disease from the very beginning, with distinct homing preferences in tumor cells. Organs most commonly involved during the lengthy course of the disease are, in descending frequency, lymph node/peripheral blood, liver, spleen, lung, bone marrow, GI tract, pancreas, and kidney. PMID:26321404

  13. 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

  14. Mycosis fungoides: carcinogens and cerebral involvement.

    PubMed

    Conrad, M E; Omura, G A

    1987-02-01

    Three patients with mycosis fungoides, who were long-term employees of a manufacturer of solid fuel propellants, were seen. Two of these patients had tumorous involvement of the central nervous system, which was successfully treated with radiation therapy. The potential relationship of carcinogens is discussed.

  15. Granulomatous mycosis fungoides--a diagnostic challenge.

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-02-01

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

  17. 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

  18. 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

  19. Acral Mycosis Fungoides With Epidermal Microvesiculation Mucinosis.

    PubMed

    Riveiro-Falkenbach, Erica; Ruano, Yolanda; Garrido, Maria; Ortiz-Romero, Pablo L; Rodríguez-Peralto, José Luis

    2015-08-01

    Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma. This entity may present with a wide spectrum of clinicopathological manifestations and mimic different dermatoses. Among its histopathological variants, spongiosis is an infrequent finding, and spongiotic microvesiculation is particularly rare. Mucinous deposition is a common event in folliculosebaceous units of folliculotropic MF but rarely described within the epidermis. Herein, we report a patient with eczematous palmoplantar lesions whereby the histological, immunohistochemical, and molecular studies confirmed to be a unique case of MF showing epidermal microvesiculation mucinosis.

  20. Correlation between mycosis fungoides and pregnancy

    PubMed Central

    Naeini, Farahnaz Fatemi; Abtahi-naeini, Bahareh; Najafian, Jamshid; Saffaei, Ali; Pourazizi, Mohsen

    2016-01-01

    Objectives: To evaluate the effect of pregnancy on the natural course of Mycosis fungoides (MF) and compare the obtained results with previous reports. Methods: The medical records of 140 patients with cutaneous T-cell lymphoma (CTCL) treated at the University Hospital of Isfahan (the academic referral center for CTCL) Isfahan, Iran. Between 2000 and 2013 were retrospectively reviewed to retrieve all cases of pregnancy during the course of MF disease. Results: A total of 8 pregnancies were recorded. The median age of patients at the time of diagnosis was 26.7 (range 21-30 years) and pregnancy 29.4 (range 27-31 years). Most of patients had early-stage MF (Ia and Ib). All patients experienced aggravation of disease during pregnancy or immediately postpartum. Mycosis fungoides did not cause any complications during pregnancy. Conclusion: Pregnancy appears to have a negative impact on the course of MF, probably due to immune system deteriorations during the pregnancy. Further studies are needed to clarify the interplay between pregnancy and MF. PMID:27570852

  1. 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.

  2. 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

  3. 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

  4. Juvenile folliculotropic and ichthyosiform mycosis fungoides.

    PubMed

    Ryan, C; Whittaker, S; D'Arcy, C; O'Regan, G M; Rogers, S

    2009-07-01

    Ichthyosiform mycosis fungoides (MF) is a recently recognized clinical variant of MF, which appears as dry scaling patches and plaques, or as a generalized eruption. Acquired ichthyosis is well recognized as a paraneoplastic cutaneous presentation of malignancy, especially in lymphoproliferative disorders. In contrast, the ichthyosiform eruption in ichthyotic MF is attributable to infiltration of the skin by tumour cells. We report the case of a 15-year-old boy who presented with a 5-year history of enlarging pruritic plaques on the forehead and back, patchy alopecia and generalized ichthyosis. Histology of the forehead and back showed a dense, lymphocytic, folliculocentric and perivascular infiltrate of predominantly CD4-positive T cells consistent with folliculotropic MF. Histological examination of biopsies from ichthyotic skin found similar features. Our patient had a histological diagnosis at the age of 15 years, making him the youngest reported patient with either folliculotropic MF or ichthyotic MF.

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

    PubMed

    Furue, Masutaka; Kadono, Takafumi

    2015-10-01

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

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

    PubMed

    Furue, Masutaka; Kadono, Takafumi

    2015-10-01

    Mycosis fungoides and Sézary syndrome are T-helper (Th)2-skewed cutaneous lymphomas. The clinical course of mycosis fungoides is classically indolent, manifesting as patches, plaques and tumors. Along with their progression, Th2 dominance tends to be accelerated. In this review, we discuss the epidemiology, clinicopathogenetic features and therapeutic approaches in mycosis fungoides and Sézary syndrome. PMID:26432429

  7. 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.

  8. 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

  9. 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

  10. Cutaneous malignant melanoma in association with mycosis fungoides.

    PubMed

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

    2004-05-01

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

  11. Cutaneous necrosis associated with the antiphospholipid syndrome and mycosis fungoides.

    PubMed

    Hill, V A; Whittaker, S J; Hunt, B J; Liddell, K; Spittle, M F; Smith, N P

    1994-01-01

    The development of extensive cutaneous necrosis in a patient with tumour-stage mycosis fungoides is described. Skin biopsies showed a lymphomatous infiltrate, and thrombosis of dermal blood vessels. Investigation revealed the presence of anticardiolipin antibodies, a lupus anticoagulant, and low free protein S, which contributed to a prothrombotic state. Antiphospholipid antibodies have been detected in non-Hodgkin's lymphoma, but clinical manifestations are uncommon. Such autoantibodies may be produced by neoplastic lymphoid cells. The frequency with which antiphospholipid antibodies occur in mycosis fungoides is currently unknown.

  12. Granulomatous mycosis fungoides presenting as an acquired ichthyosis.

    PubMed

    Eisman, S; O'Toole, E A; Jones, A; Whittaker, S J

    2003-03-01

    We report a case of a 69-year-old gentleman who presented with a 3-month history of unexplained fevers and malaise who developed generalized pruritus, alopecia and an ichthyosiform erythematous eruption on his forearms, legs, chest and back. Skin histology, immunophenotyping and molecular features were consistent with granulomatous mycosis fungoides. He has been successfully treated with twice weekly PUVA photochemotherapy.

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

    PubMed

    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

  14. 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

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

    PubMed

    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.

  16. Mycosis Fungoides, Then and Now… Have We Travelled?

    PubMed

    Mahalingam, Meera; Reddy, Vijaya B

    2015-11-01

    Mycosis fungoides (MF) is the most common type of cutaneous lymphoma, accounting for almost 50% of all primary cutaneous lymphomas. When initially described, it was believed to be a distinct clinical entity with a pathognomonic histopathologic picture. Through the years we have come to know that, like syphilis, MF is a great masquerader and can present clinically and histopathologically in many ways. This review is an attempt to cover the many faces of MF that have evolved through the years.

  17. A case of acanthosis nigricans coexisting with mycosis fungoides.

    PubMed

    Cheng, Esther; Roy, David B; Magro, Cynthia M

    2015-07-01

    Acanthosis nigricans maligna (ANM) is a paraneoplastic phenomenon most commonly associated with visceral adenocarcinoma, in particular, gastric adenocarcinoma. Clinically, AMN is characterized by rapidly progressive symmetrical skin thickening and hyperpigmentation of the intertriginous areas with peripheral acrochorda. The diagnosis is made by a detailed medical work-up for occult malignancies with particular emphasis on endocrinological diseases. We report a 67-year-old man that presented clinically with acanthosis nigricans, in which a subsequent diagnosis of mycosis fungoides was made.

  18. Mycosis Fungoides, Then and Now… Have We Travelled?

    PubMed

    Mahalingam, Meera; Reddy, Vijaya B

    2015-11-01

    Mycosis fungoides (MF) is the most common type of cutaneous lymphoma, accounting for almost 50% of all primary cutaneous lymphomas. When initially described, it was believed to be a distinct clinical entity with a pathognomonic histopathologic picture. Through the years we have come to know that, like syphilis, MF is a great masquerader and can present clinically and histopathologically in many ways. This review is an attempt to cover the many faces of MF that have evolved through the years. PMID:26452212

  19. A case of acanthosis nigricans coexisting with mycosis fungoides.

    PubMed

    Cheng, Esther; Roy, David B; Magro, Cynthia M

    2015-07-01

    Acanthosis nigricans maligna (ANM) is a paraneoplastic phenomenon most commonly associated with visceral adenocarcinoma, in particular, gastric adenocarcinoma. Clinically, AMN is characterized by rapidly progressive symmetrical skin thickening and hyperpigmentation of the intertriginous areas with peripheral acrochorda. The diagnosis is made by a detailed medical work-up for occult malignancies with particular emphasis on endocrinological diseases. We report a 67-year-old man that presented clinically with acanthosis nigricans, in which a subsequent diagnosis of mycosis fungoides was made. PMID:26436975

  20. Prominent Vascular and Perivascular Eosinophilic Infiltrates Heralding CNS Mycosis Fungoides.

    PubMed

    Schowinsky, Jeffrey; Leppert, Michelle; Ney, Douglas; Kleinschmidt-DeMasters, B K

    2015-10-01

    Brain parenchymal involvement of mycosis fungoides (MF) is very rare. This study reports a patient with known cutaneous MF (under treatment) who presented with a CNS syndrome and multiple brain lesions. Brain biopsy demonstrated massive eosinophilic infiltrates but no MF cells. Despite treatment, new lesions developed and the patient died. At autopsy, there was massive involvement MF cells, suggesting that the eosinophilic infiltrates presaged the severe involvement of the CNS by MF. PMID:26352990

  1. CD8-positive Mycosis Fungoides Masquerading as Pyoderma Gangrenosum

    PubMed Central

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

    2016-01-01

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

  2. CD8-positive Mycosis Fungoides Masquerading as Pyoderma Gangrenosum

    PubMed Central

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

    2016-01-01

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

  3. CD8-positive Mycosis Fungoides Masquerading as Pyoderma Gangrenosum.

    PubMed

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

    2016-01-01

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

  4. CD8-positive Mycosis Fungoides Masquerading as Pyoderma Gangrenosum.

    PubMed

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

    2016-01-01

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

  5. Methotrexate-induced necrolysis in tumoral-stage mycosis fungoides: a challenging diagnosis.

    PubMed

    Mna, Amira Ben; Souissi, Asmahene; Halouani, Slim; El Euch, Dalenda; Zahani, Alia; Kchir, Nidham; Zaraa, Ines; Mokni, Mourad

    2016-01-01

    Methotrexate-induced cutaneous ulceration is a rare but potentially serious drug adverse reaction. This adverse reaction of methotrexate therapy has been initially described in psoriasis patients and is unusual in patients with cutaneous T-cell lymphoma. In 1978, Mc Donald et al reported the first three cases of cutaneous ulcerations in patients treated for a mycosis fungoides with intravenous infusions of methotrexate. Since then, few cases of methotrexate-induced skin ulcers in patients with mycosis fungoides have been published. We report an additional patient with erythrodermic mycosis fungoides who developed cutaneous ulcerations as a sole manifestation of methotrexate toxicity.

  6. Leser-Trélat Sign in Tumor-Stage Mycosis Fungoides.

    PubMed

    Rowe, Brandon; Shevchenko, Alina; Yosipovitch, Gil

    2016-01-01

    A 71-year-old man presented with numerous pruritic seborrheic keratoses, with an eruptive onset over the course of 3 months. At presentation, he was also found to have hypopigmented tumors diffusely scattered throughout his body that were found to be mycosis fungoides on histologic examination. A theory regarding the pathophysiology of the development of eruptive seborrheic keratoses in the presence of mycosis fungoides is briefly discussed and 10 previous case reports of the Leser-Trélat sign in the setting of mycosis fungoides are reviewed.

  7. Interstitial Mycosis Fungoides: A Clinicopathologic Study of 21 Patients.

    PubMed

    Reggiani, Camilla; Massone, Cesare; Fink-Puches, Regina; Cota, Carlo; Cerroni, Lorenzo

    2016-10-01

    Interstitial mycosis fungoides (IMF) is a rare histopathologic variant of mycosis fungoides (MF) that may mimic other inflammatory dermatoses, mainly interstitial granuloma annulare, inflammatory morphea, and interstitial granulomatous dermatitis. Only small series and sporadic case reports of IMF have been described in the literature. We reviewed 27 specimens from 21 patients with IMF (M:F=11:10, median age 60) to better characterize clinical, histopathologic, and immunohistochemical features of this disease. Most patients presented clinically with patches and/or plaques. Conventional MF was documented before, concomitant with, or after IMF in 12 patients, whereas only in 2 patients different biopsies showed exclusive features of IMF over a period of 4 and 191 months, respectively. Histology revealed in all cases variably long, linear aggregates of dermal lymphocytes splaying the collagen fibers, involving predominantly the superficial and mid-dermis (6 cases) or the entire dermis (21 cases). Immunohistochemical stainings revealed a cytotoxic phenotype in 9/18 tested cases. Variable amounts of histiocytes/macrophages were found interstitially in all tested biopsies but never represented a population larger than that of T lymphocytes. Our study shows that IMF is a peculiar variant of MF with frequent cytotoxic phenotype. This histopathologic variant in most cases represents a transient pattern in otherwise conventional MF. Accurate clinicopathologic correlation and phenotypic studies of atypical dermal interstitial lymphohistiocytic infiltrates allow to make a correct diagnosis.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Practical Aspects Regarding the Histopathological Diagnosis of Early Mycosis Fungoides.

    PubMed

    Tebeică, T; Andrei, R; Zurac, Sabina; Stăniceanu, Florica

    2016-01-01

    Mycosis fungoides is the most common primary T-cell lymphoma of skin. The disease has a protean clinical and histological presentation in its early patch and plaque stages, when distinction from mimicking inflammatory dermatoses is difficult. Since no single criterion is specific enough, a reliable diagnosis in early stages requires integration of clinical, histopathological and molecular findings. In skin biopsies, the most helpful histologic features are the detection of atypical lymphocytes in the epidermis with minimal epidermal changes, basal alignment of lymphocytes along dermal-epidermal junction and formation of Pautrier microabscesses. An aberrant immunophenotype of T cells and molecular detection of a clonal T-cell population are factors that could allow a more specific diagnosis. This work recapitulates and discusses these features from a practical perspective. PMID:27141565

  14. Coincidental association of mycosis fungoides and occupational systemic sclerosis?

    PubMed

    Yasuda, Masahito; Amano, Hiroo; Yamanaka, Masayoshi; Tamura, Atsushi; Ishikawa, Osamu

    2008-01-01

    We report a 58-year-old man with mycosis fungoides (MF) and occupational systemic sclerosis (SSc) induced by silica exposure. He was engaged in tunnel construction from the age of 18 to 33 years. He developed MF at the age of 30. Diagnosis of silicosis was made at the age of 52 and SSc at the age of 58. Physical examinations revealed sclerotic skin changes on his forearms and fingers and poikiloderma on the left popliteal fossa and inguinal region. Both antinuclear antibody and antitopoisomerase-I antibody were positive. We could find no apparent difference between his clinical features and those of idiopathic SSc except for the presence of silicosis and MF. Systemic therapy with interferon-gamma for MF did not improve the skin sclerosis. We discuss the relationship of silica exposure to both MF and SSc.

  15. Early morphea simulating patch-stage mycosis fungoides.

    PubMed

    Fujimoto, Masakazu; Basko-Plluska, Juliana L; Petronic-Rosic, Vesna; Shea, Christopher R

    2015-05-01

    Morphea is a rare fibrosing condition of the skin and underlying tissues characterized histopathologically by thickened collagen bundles throughout the dermis, loss of adnexal structures, and "fat trapping." In the early stages of morphea, the absence of the fully developed characteristic findings may cause diagnostic confusion for the practicing pathologist. The authors report an unusual case of early morphea misdiagnosed as patch-stage poikilodermatous mycosis fungoides (MF) based on the initial clinical, histopathologic, and molecular findings. However, as time elapsed, well-developed lesions revealed clinical and histopathologic features diagnostic of morphea. The authors report this case to illustrate that lesions of early morphea may simulate MF. Given the similarities in clinicopathologic presentation, dermatologists and dermatopathologists should be cautious not to inadvertently misinterpret early morphea as MF.

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

    PubMed

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

    2014-12-23

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

  17. Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor.

    PubMed

    Ceriolo, Paola; Fausti, Valentina; Cinotti, Elisa; Bonadio, Silvia; Raffaghello, Lizzia; Bianchi, Giovanna; Orcioni, Giulio Fraternali; Fiocca, Roberto; Rongioletti, Franco; Pistoia, Vito; Borgonovo, Giacomo

    2016-03-28

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that can undergo local progression with possible systemic dissemination. We report a case of a patient affected by MF with a pancreatic mass that was a diagnostic challenge between primitive tumor and pancreatic metastasis from MF. Clinical setting findings and imaging studies raised the suspicion of a pancreatic primary neoplasm. A diagnostic clue was provided by the combined histomorphologic/immunohistochemical study of pancreatic and cutaneous biopsies, which revealed a pancreatic localization of MF. Considering the rarity of metastatic localization of MF to the pancreas, we next investigated whether chemokine-chemokine receptor interactions could be involved in the phenomenon to provide new insight into the possible mechanisms underlying metastatic localization of MF to the pancreas. Histological analyses of archival pancreatic tissue demonstrated that glucagon-secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may have attracted in our case metastatic MF cells expressing the complementary receptor CCR10.

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

    PubMed

    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; Eischen, Christine M

    2015-07-23

    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.

  19. Practical Aspects Regarding the Histopathological Diagnosis of Early Mycosis Fungoides.

    PubMed

    Tebeică, T; Andrei, R; Zurac, Sabina; Stăniceanu, Florica

    2016-01-01

    Mycosis fungoides is the most common primary T-cell lymphoma of skin. The disease has a protean clinical and histological presentation in its early patch and plaque stages, when distinction from mimicking inflammatory dermatoses is difficult. Since no single criterion is specific enough, a reliable diagnosis in early stages requires integration of clinical, histopathological and molecular findings. In skin biopsies, the most helpful histologic features are the detection of atypical lymphocytes in the epidermis with minimal epidermal changes, basal alignment of lymphocytes along dermal-epidermal junction and formation of Pautrier microabscesses. An aberrant immunophenotype of T cells and molecular detection of a clonal T-cell population are factors that could allow a more specific diagnosis. This work recapitulates and discusses these features from a practical perspective.

  20. Folliculotropic Mycosis Fungoides as a Posttransplant Lymphoproliferative Disorder.

    PubMed

    Spence-Shishido, Allyson; Streicher, Jenna L; George, Roshan P; Parker, Sareeta R; Lawley, Leslie P

    2015-09-01

    Posttransplant lymphoproliferative disorder (PTLD) is a known complication of solid organ transplantation. The majority are B cell in origin and related to Epstein-Barr virus infection. T-cell PTLD is much less common; most are Epstein-Barr virus negative and have a worse prognosis. Primary cutaneous T-cell lymphoma (CTCL) as a presentation of PTLD is rare. CTCL has a less favorable prognosis in transplant patients compared with that in immune-competent patients. Herein, we report a case of a 13-year-old boy who developed folliculotropic mycosis fungoides, a rare subtype of CTCL, subsequent to renal transplantation. To our knowledge, this is the first report of this type of PTLD in a pediatric patient. PMID:26283779

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

    ClinicalTrials.gov

    2016-08-11

    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

  2. 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

  3. 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

  4. How I treat mycosis fungoides and Sézary syndrome.

    PubMed

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

    2009-11-12

    The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a "stage-based" approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-alpha, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used.

  5. 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.

  6. 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

  7. 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

  8. Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor

    PubMed Central

    Ceriolo, Paola; Fausti, Valentina; Cinotti, Elisa; Bonadio, Silvia; Raffaghello, Lizzia; Bianchi, Giovanna; Orcioni, Giulio Fraternali; Fiocca, Roberto; Rongioletti, Franco; Pistoia, Vito; Borgonovo, Giacomo

    2016-01-01

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that can undergo local progression with possible systemic dissemination. We report a case of a patient affected by MF with a pancreatic mass that was a diagnostic challenge between primitive tumor and pancreatic metastasis from MF. Clinical setting findings and imaging studies raised the suspicion of a pancreatic primary neoplasm. A diagnostic clue was provided by the combined histomorphologic/immunohistochemical study of pancreatic and cutaneous biopsies, which revealed a pancreatic localization of MF. Considering the rarity of metastatic localization of MF to the pancreas, we next investigated whether chemokine-chemokine receptor interactions could be involved in the phenomenon to provide new insight into the possible mechanisms underlying metastatic localization of MF to the pancreas. Histological analyses of archival pancreatic tissue demonstrated that glucagon-secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may have attracted in our case metastatic MF cells expressing the complementary receptor CCR10. PMID:27022231

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

    PubMed Central

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

    2016-01-01

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

  10. 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

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

    PubMed Central

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

    2016-01-01

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

  12. Poikilodermatous mycosis fungoides: clinical and histopathological analysis of a case and literature review.

    PubMed

    Pankratov, Oleg; Gradova, Svetlana; Tarasevich, Svetlana; Pankratov, Valentin

    2015-01-01

    Poikilodermatous mycosis fungoides is a rare distinct clinical variant of cutaneous T-cell lymphoma (CTCL), formerly referred to as poikiloderma vasculare atrophicans or parapsoriasis variegata. Mycosis fungoides (MF) is a malignant neoplasm of T-lymphocyte origin, most commonly memory CD4+ T-cells.We report here a patient with generalized poikilodermatous skin lesions whose diagnosis of mycosis fungoides was made only a few years after the onset of his disease due to its bizarre clinical behavior and a natural reluctance to diagnose this disease in children and adolescents.The variability of atypical clinical presentations of MF and its similarity to benign inflammatory and noninflammatory skin disorders may become a source of considerable confusion and controversy, challenging a dermatologist to make a precise diagnosis. Therefore, scrupulous clinicopathological correlation is an absolute necessity.

  13. 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.

  14. Demodex folliculitis on the trunk of a patient with mycosis fungoides.

    PubMed

    Nakagawa, T; Sasaki, M; Fujita, K; Nishimoto, M; Takaiwa, T

    1996-03-01

    A 43-year-old man with tumour stage mycosis fungoides developed multiple follicular pustules on the trunk during total-skin electron beam therapy. A potassium hydroxide preparation of the contents of the pustules revealed the presence of Demodex mites. The patient was treated with 6% sulphur lotion with rapid improvement of the cutaneous lesions. We believe that this case represents a pustular folliculitis caused by Demodex mites. Immunosuppression associated with mycosis fungoides and its treatment may have resulted in the proliferation of this obligate parasite of the pilosebaceous follicle, and the development of the folliculitis.

  15. Nodular Prurigo Associated with Mycosis Fungoides - Case Report.

    PubMed

    Jerković Gulin, Sandra; Čeović, Romana; Lončarić, Davorin; Ilić, Ivana; Radman, Ivo

    2015-01-01

    Mycosis fungoides (MF) is the most common type of cutaneous lymphoma and accounts for approximately 50% of all lymphomas arising primarily in the skin. The three types of MF lesions are patches, plaques, and tumors, according to which the disease is traditionally divided into three clinical stages. The clinical course can be protracted and take years or decades. In the final stage, MF evolves to a systemic form of the disease. Nodular prurigo (NP) is still a condition of unknown etiology characterized by papulonodular eruption and intense pruritus. Multiple diseases, including dermatological, systemic, and psychiatric diseases, have been assumed to cause NP. Pruritic skin lesions have been known to precede clinically evident B and T cell lymphomas for years. In the literature, pruritus and NP have been reported in patients affected by systemic Hodgkin and non-Hodgkin lymphomas. Only two cases of cutaneous lymphoma as underlying disease in patients with PN have been reported in the literature. We report a rare case of a patient with concomitant non-Hodgkin skin lymphoma - MF and NP. Our female patient with a 10-year history of MF stage IIb during the last three years had been presenting for regular check-up with itchy, newly formed, rarely disseminated nodules 5-8 mm in diameter on the forearms and lower legs. Sharply limited erythematosquamous, slightly infiltrated foci (as part of MF as the underlying disease) were visible on the trunk and extremities. Extracutaneous involvement of MF was excluded. We performed a biopsy on a nodule from the lower leg to rule out tumor stage MF; the biopsy confirmed NP. We conclude that prurigo nodules should not be confused with tumor stage MF. NP is a therapeutic challenge for any dermatologist. Any underlying diseases should be treated first. PMID:26476905

  16. Hodgkin Lymphoma in a patient with mycosis fungoides: molecular evidence for separate cellular origins.

    PubMed

    Sidwell, R U; McLaughlin, J E; Jones, A; Whittaker, S J

    2003-04-01

    We report the case of a man with mycosis fungoides (MF), who, 11 years after diagnosis, developed Hodgkin's disease. Although MF is associated with a higher than expected prevalence of other malignancies, including Hodgkin lymphoma, analysis of cells from the skin and lymph nodes showed findings that suggest a separate cellular origin for the two diseases.

  17. [Mycosis fungoides or inflammatory dermatitis: differential diagnosis between early lymphoma and inflammation in skin biopsies].

    PubMed

    Oschlies, I; Klapper, W

    2013-05-01

    Mycosis fungoides is a cutaneous T-cell lymphoma with protracted clinical course and progression in different stages with increasing aggressiveness. The clinical picture as well as the histopathology of mycosis fungoides within the early patch and plaque phase is difficult to delineate from some inflammatory skin diseases. Thus, the diagnosis of these early stages of the lymphoma is only possible when clinical, histopathological, and molecular features are integrated into the diagnosis, especially as none of the individual disease criteria is specific. Important clues towards the diagnosis of mycosis fungoides are cytologically abnormal epidermotropic CD4-positive T-cells causing only minor epidermal alterations, the formation of Pautrier-abscesses and basal alignment of the epidermotropic T-cells. The findings of an aberrant T-cell immunophenotype of the intraepidermal lymphoid component as well as the molecular proof of T-cell clonality are important further features. In the differential diagnosis between early stage mycosis fungoides and parapsoriasis, there remains nevertheless a diagnostic and maybe also a true biological grey zone. PMID:23549914

  18. 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.

  19. 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

  20. 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.

  1. Innovative Approaches to Radiation Treatment for Mycosis Fungoides in the Setting of Collagen Vascular Disease

    PubMed Central

    Terezakis, Stephanie A.; Bohle, George C.; Lo, Ying-Chun; Berry, Sean L.; Yahalom, Joachim

    2015-01-01

    Patients with connective tissue disorders are clinically challenging for radiation oncologists as these patients may be at increased risk for radiation-related skin toxicity. A clinical dilemma presents itself in a patient with lupus who presents with confluent skin lesions from mycosis fungoides requiring radiotherapy. In this report, we discuss an innovative technique used to develop an immobilization device that also effectively functioned as a uniform bolus with distinct dosimetric advantages to the use of a facial moulage. PMID:26413361

  2. Frequent abnormalities of the p15 and p16 genes in mycosis fungoides and sezary syndrome.

    PubMed

    Scarisbrick, Julia J; Woolford, Alison J; Calonje, Eduardo; Photiou, Andrew; Ferreira, Sylvia; Orchard, Guy; Russell-Jones, Robin; Whittaker, Sean J

    2002-03-01

    There are few data on the molecular pathogenesis of cutaneous T cell lymphomas. A recent allelotyping study by our group identified frequent allelic loss on 9p, 10q, and 17p including losses on 9p21 in 16% of patients with mycosis fungoides and 46% with Sezary syndrome. The P15 and P16 genes are intricately linked on 9p21 and can be inactivated in melanoma and non-Hodgkin's lymphoma. We have therefore studied 76 patients with either mycosis fungoides or Sezary syndrome for abnormalities of these genes. DNA samples were analyzed for loss of heterozygosity, homozygous deletion, intragenic mutations, and promoter methylation. In addition P15 and P16 protein expression was assessed. Microsatellite analysis was informative in 73 of 76 cases: allelic loss on 9p21 was identified in 18 patients (25%), including 12 of 57 with mycosis fungoides (21%) and six of 16 with Sezary syndrome (37%). Single strand conformation polymorphism analysis of the entire coding regions of both genes did not identify any mutations, although two polymorphisms were identified including C613A, which has not previously been described. P15 and P16 gene promoter methylation was found in 45% and 29% of patients, respectively. Furthermore aberrant P15 protein expression was detected in 85% of patients analyzed with P15 gene abnormalities and abnormal P16 expression in 59% with P16 gene abnormalities. These abnormalities were not dependent on cutaneous stage of disease. This study suggests that abnormalities of the P15 and P16 genes are common in both early and advanced stages of mycosis fungoides and Sezary syndrome and that these genes may be inactivated by allelic loss and aberrant promoter methylation.

  3. Durable remission of folliculotropic mycosis fungoides achieved with a combined topical treatment with cytarabine and carmustine.

    PubMed

    Heisig, Monika; Maj, Joanna; Szepietowski, Jacek C; Reich, Adam

    2016-01-01

    Folliculotropic mycosis fungoides (MF) is an uncommon subtype of MF which has a more aggressive natural history and is more resistant to treatment than other forms of MF. In this article, an innovative method of treatment is presented. We describe a successful use of topical cytarabine combined with topical carmustine in a patient with a folliculotropic MF. Based on our patient history we suggest this method as an effective therapy option for patients with folliculotropic MF unresponsive to other forms of treatment.

  4. Innovative Approaches to Radiation Treatment for Mycosis Fungoides in the Setting of Collagen Vascular Disease.

    PubMed

    Terezakis, Stephanie A; Bohle, George C; Lo, Ying-Chun; Berry, Sean L; Yahalom, Joachim

    2015-01-01

    Patients with connective tissue disorders are clinically challenging for radiation oncologists as these patients may be at increased risk for radiation-related skin toxicity. A clinical dilemma presents itself in a patient with lupus who presents with confluent skin lesions from mycosis fungoides requiring radiotherapy. In this report, we discuss an innovative technique used to develop an immobilization device that also effectively functioned as a uniform bolus with distinct dosimetric advantages to the use of a facial moulage. PMID:26413361

  5. IL32 is progressively expressed in mycosis fungoides independent of helper T-cell 2 and helper T-cell 9 polarization.

    PubMed

    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

    2014-09-01

    Mycosis fungoides, 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 patients with mycosis fungoides (n = 21), healthy volunteers (n = 17), and individuals with atopic dermatitis (n = 17) and psoriasis (n = 9), we found IL32 mRNA expression significantly higher in mycosis fungoides samples than in samples from benign inflammatory skin diseases, and its expression increases with disease progression. By IHC and immunofluorescence, we confirmed IL32 protein expression in many CD3(+)CD4(+) T cells and some epidermotropic T cells in mycosis fungoides lesions. MyLa cells (a mycosis fungoides cell line) express IL32, which, in turn, could promote cellular proliferation and viability in a dose-dependent fashion. IL32-treated MyLa and CTCL HH cells upregulated cell proliferation and survival genes. Of the major "polarizing" T-cell cytokines, only IFNγ mRNA increases with mycosis fungoides progression and positively correlates with IL32 mRNA expression. Th2 cytokines do not positively correlate with IL32 mRNA expression or mycosis fungoides progression. Furthermore, by flow cytometry, IL32 production by circulating activated T cells in healthy individuals was found in both IFNγ(+) and IFNγ(-) cells but not in IL4(+) or IL13(+) cells. In conclusion, we have identified IL32(+) cells as the likely tumor cells in mycosis fungoides, and demonstrated that IL32 mRNA expression increases with mycosis fungoides progression and is significantly higher than mRNA expression in other skin diseases, and that some IL32(+) T cells are independent from the defined Th subsets. Thus, IL32 may play a unique role in mycosis fungoides progression as an autocrine cytokine.

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

    PubMed

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

    2012-08-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  9. A practical approach to accurate classification and staging of mycosis fungoides and Sézary syndrome.

    PubMed

    Thomas, Bjorn Rhys; Whittaker, Sean

    2012-12-01

    Cutaneous T-cell lymphomas are rare, distinct forms of non-Hodgkin's lymphomas. Of which, mycosis fungoides (MF) and Sézary syndrome (SS) are two of the most common forms. Careful, clear classification and staging of these lymphomas allow dermatologists to commence appropriate therapy and allow correct prognostic stratification for those patients affected. Of note, patients with more advanced disease will require multi-disciplinary input in determining specialist therapy. Literature has been summarized into an outline for classification/staging of MF and SS with the aim to provide clinical dermatologists with a concise review.

  10. [A case of cutaneous epitheliotropic malignant lymphoma (mycosis fungoides) in a horse].

    PubMed

    Hilbe, M; Meier, D; Feige, K

    1997-03-01

    This article describes an eleven year old mare with apathy, fever, enlarged mandibular lymph nodes, skin lesions on the upper lip and edematous, grey-red mucous membranes in the nose, mouth and vulva. Histopathology revealed infiltrates with atypical lymphocytes forming Pautrier's microabscesses. The neoplastic cells had large, often indented nuclei. Immunohistology showed that some cells were CD3-positive (Pan T-cell-marker). The diagnosis of cutaneous epitheliotropic malignant lymphoma (Mycosis fungoides) was made. The etiology in the horse is unknown. PMID:9157840

  11. 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.

  12. 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.

  13. 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

  14. Durable remission of folliculotropic mycosis fungoides achieved with a combined topical treatment with cytarabine and carmustine.

    PubMed

    Heisig, Monika; Maj, Joanna; Szepietowski, Jacek C; Reich, Adam

    2016-01-01

    Folliculotropic mycosis fungoides (MF) is an uncommon subtype of MF which has a more aggressive natural history and is more resistant to treatment than other forms of MF. In this article, an innovative method of treatment is presented. We describe a successful use of topical cytarabine combined with topical carmustine in a patient with a folliculotropic MF. Based on our patient history we suggest this method as an effective therapy option for patients with folliculotropic MF unresponsive to other forms of treatment. PMID:26278921

  15. 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.

  16. Folliculotropic mycosis fungoides (stage IIA) progressing to Sézary syndrome: a case report.

    PubMed

    Agar, N; Whittaker, S J

    2008-11-01

    Folliculotropic mycosis fungoides is associated with a worse prognosis than classical mycosis fungoides (MF), but whether this is due to resistance to skin-directed therapy or to biological differences is unclear. We discuss a case of a patient with folliculotropic MF (stage IIA) who progressed to develop Sézary syndrome (SS), stage IVB, over 6 years. A 40-year-old man presented with pruritic plaques affecting his head and trunk, characterized by follicular plugging. The histology was consistent with folliculotropic MF and T-cell gene analysis studies revealed a T-cell clone in the skin only. His condition gradually deteriorated and 5 years after presentation, T-cell gene analysis studies revealed the presence of a clone in the blood identical with that seen in the skin. His condition progressed with the development of erythrodermic disease and a leukaemic blood picture and he subsequently died of systemic nodal and visceral involvement. We present the first report detailing the stepwise progression of a patient with stage IIA folliculotropic MF to SS. This case demonstrates that MF and SS represent a clinical spectrum of the same disease.

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

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

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

    PubMed

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

    2015-04-01

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

  19. 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.

  20. 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.

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

    PubMed

    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

  2. Microsatellite instability is associated with hypermethylation of the hMLH1 gene and reduced gene expression in mycosis fungoides.

    PubMed

    Scarisbrick, Julia J; Mitchell, Tracey J; Calonje, Eduardo; Orchard, Guy; Russell-Jones, Robin; Whittaker, Sean J

    2003-10-01

    Fifty-one mycosis fungoides samples were analyzed for microsatellite instability (MSI) using the panel of markers recommended for hereditary nonpolyposis colorectal cancer kindred and a panel we designed for cutaneous T cell lymphoma in order to compare detection rates and determine if MSI is a genome-wide phenomenon. Samples demonstrating MSI were analyzed for abnormalities of the hMLH1 gene including loss of heterozygosity, mutations, and promoter hypermethylation. MSI was detected in 16% using the hereditary nonpolyposis colorectal cancer panel and 22% with the cutaneous T cell lymphoma panel. Overall, 27% demonstrated MSI and 73% had a stable phenotype. hMLH1 gene studies did not detect loss of heterozygosity or reveal any mutations. Promoter hypermethylation was detected in nine of 14 patients with MSI, however (64%). In addition hMLH1 and hMSH2 protein expression was studied using immunohistochemical techniques. Five of nine patients with MSI and hMLH1 promoter methylation showed abnormal hMLH1 protein expression with normal hMSH2 gene expression. All other patients tested demonstrated normal hMLH1 and hMSH2 protein expression. MSI was found to be more prevalent in tumor stage mycosis fungoides (47%) than early stage disease (20%) and was associated with an older age of onset of mycosis fungoides. MSI may be a consequence of hMLH1 promoter hypermethylation in mycosis fungoides patients and may prevent transcription in a subset of patients. This suggests that the development of a mutator phenotype may contribute to disease progression in mycosis fungoides.

  3. 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

  4. Childhood mycosis fungoides with a CD8+ CD56+ cytotoxic immunophenotype.

    PubMed

    Poppe, Heiko; Kerstan, Andreas; Böckers, Martin; Goebeler, Matthias; Geissinger, Eva; Rosenwald, Andreas; Hamm, Henning

    2015-04-01

    Primary cutaneous T-cell lymphomas mostly occur in patients of middle and higher age. Their rarity and an oftentimes atypical clinical presentation in childhood as well as the reluctance of taking biopsies in children are reasons for a delayed diagnosis. We report the case of an 11-year-old boy with a 7-year history of slowly progressive CD8+CD56+ mycosis fungoides of the cytotoxic immunophenotype. His trunk and extremities were affected by extensive pale-erythematous patches and plaques with fine scaling. In addition, several poikilodermatous lesions were present on his thighs. Improvement was achieved by topical mometasone furoate treatment. On the basis of our observation, a brief review on cutaneous T-cell lymphomas in childhood and on CD8+ subtypes in particular is given. Clinicopathological correlation is crucial for establishing the correct diagnosis and for estimation of the prognosis.

  5. Hematopoietic Stem Cell Transplant for Mycosis Fungoides and Sézary Syndrome.

    PubMed

    Virmani, Pooja; Zain, Jasmine; Rosen, Steven T; Myskowski, Patricia L; Querfeld, Christiane

    2015-10-01

    Mycosis fungoides (MF) and Sézary syndrome (SS) are common types of primary cutaneous T-cell lymphoma. Early-stage MF has a favorable prognosis and responds well to skin-directed regimens. Patients with advanced-stage MF, transformed MF, and SS are treated with combined systemic and skin-directed therapies. However, the disease is incurable with standard regimens, and frequent relapses are common. Owing to the lack of improvement in overall survival with standard regimens, hematopoietic stem cell transplant (HSCT) has been explored as a potential curative option. This article reviews the role of HSCT in MF/SS and discusses data regarding conditioning regimens, treatment-related complications, and outcomes.

  6. Hematopoietic Stem Cell Transplant for Mycosis Fungoides and Sézary Syndrome.

    PubMed

    Virmani, Pooja; Zain, Jasmine; Rosen, Steven T; Myskowski, Patricia L; Querfeld, Christiane

    2015-10-01

    Mycosis fungoides (MF) and Sézary syndrome (SS) are common types of primary cutaneous T-cell lymphoma. Early-stage MF has a favorable prognosis and responds well to skin-directed regimens. Patients with advanced-stage MF, transformed MF, and SS are treated with combined systemic and skin-directed therapies. However, the disease is incurable with standard regimens, and frequent relapses are common. Owing to the lack of improvement in overall survival with standard regimens, hematopoietic stem cell transplant (HSCT) has been explored as a potential curative option. This article reviews the role of HSCT in MF/SS and discusses data regarding conditioning regimens, treatment-related complications, and outcomes. PMID:26433851

  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. 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.

  9. 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

  10. 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

  11. 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

  12. Literature review of clinical results of total skin electron irradiation (TSEBT) of mycosis fungoides in adults

    PubMed Central

    Moraes, Fabio Ynoe de; Carvalho, Heloisa de Andrade; Hanna, Samir Abdallah; Silva, João Luis Fernandes da; Marta, Gustavo Nader

    2013-01-01

    Background Mycosis fungoides (MF) is an extranodal, indolent non-Hodgkin lymphoma of T cell origin. Even with the establishment of MF staging, the initial treatment strategy often remains unclear. Aim The aim of this study was to review the clinical results of total skin electron beam therapy (TSEBT) for MF in adults published in English language scientific journals searched in Pubmed/Medline database until December 2012. Results MF is very sensitive to radiation therapy (RT) delivered either by photons or by electrons. In limited patches and/or plaques local electron beam irradiation results in good outcomes besides the fact of not being superior to other modalities. For extensive patches and/or plaques data suggest that TSEBT shows superior response rates. The cutaneous disease presentation is favorably managed with radiotherapy due to its ability to treat the full thickness of deeply infiltrated skin. For generalized erythroderma presentation, TSEBT seems to be an appropriate initial therapy. For advanced disease, palliation, or recurrence after the first radiotherapy treatment course, TSEBT may still be beneficial, with acceptable toxicity. Recommended dose is 30–36 Gy delivered in 6–10 weeks. Conclusion TSEBT can be used to treat any stage of MF. It also presents good tumor response with symptoms of relief and a palliative effect on MF, either after previous irradiation or failure of other treatment strategies. PMID:24936326

  13. EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome.

    PubMed

    Trautinger, Franz; Knobler, Robert; Willemze, Rein; Peris, Ketty; Stadler, Rudolph; Laroche, Liliane; D'Incan, Michel; Ranki, Annamari; Pimpinelli, Nicola; Ortiz-Romero, Pablo; Dummer, Reinhard; Estrach, Teresa; Whittaker, Sean

    2006-05-01

    Several reviews and guidelines on the management of mycosis fungoides and Sézary syndrome (MF/SS) have been published; however, treatment strategies for patients with MF/SS vary from institution to institution and no European consensus has yet been established. There are few phase III trials to support treatment decisions for MF/SS and treatment is often determined by institutional experience. In order to summarise the available evidence and review 'best practices' from each national group, the European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force met in September 2004 to establish European guidelines for the treatment of MF/SS. This article reviews the treatment regimens selected for inclusion in the guidelines and summarises the clinical data for treatments appropriate for each stage of MF/SS. Guideline recommendations are presented according to the quality of supporting data, as defined by the Oxford Centre for Evidence-Based Medicine. Skin-directed therapies are the most appropriate option for early-stage MF/SS and most patients can look forward to a normal life expectancy. Patients with advanced disease should be encouraged to participate in clinical trials and maintenance of quality of life should be paramount.

  14. 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

  15. 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

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

    PubMed

    Ladrigan, Manasi Kadam; Poligone, Brian

    2014-12-01

    We report the case of a healthy 17-year-old adolescent boy with an unremarkable medical history who presented with an asymptomatic fixed rash on the abdomen, buttocks, and legs. The rash initially developed in a small area on the right leg 2 years prior and had progressed slowly. Prior biopsies were consistent with pigmented purpura. Clinical examination revealed multiple annular purpuric patches on the abdomen, buttocks, and legs covering approximately 20% of the body surface area without lymphadenopathy or hepatosplenomegaly. Additional biopsies demonstrated changes consistent with mycosis fungoides (MF). T-cell receptor g gene rearrangements demonstrated clonality. The patient was diagnosed with stage IB MF of the pigmented purpura-like variant. The patient responded well to psoralen plus UVA therapy. It has been proposed that pigmented purpuric dermatosis (PPD) is a form of cutaneous T-cell lymphoid dyscrasia and that T-cell gene rearrangement studies should be obtained for prognostic evaluation in patients with widespread disease. In our patient, the clinical appearance of the lesions, pathologic findings, and gene rearrangement studies led to the diagnosis of MF. Until the potential for evolution of PPD to malignant disease is better understood, further evaluation of MF in patients with an unusual presentation of pigmented purpura is warranted. PMID:25566571

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

    PubMed Central

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

    2016-01-01

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

  18. Allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning for mycosis fungoides and Sezary syndrome.

    PubMed

    Shiratori, Souichi; Fujimoto, Katsuya; Nishimura, Machiko; Hatanaka, Kanako C; Kosugi-Kanaya, Mizuha; Okada, Kohei; Sugita, Junichi; Shigematsu, Akio; Hashimoto, Daigo; Endo, Tomoyuki; Kondo, Takeshi; Abe, Riichiro; Hashino, Satoshi; Matsuno, Yoshihiro; Shimizu, Hiroshi; Teshima, Takanori

    2016-03-01

    Advanced-stage mycosis fungoides and Sezary syndrome (MF/SS) have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT), particularly using a reduced-intensity conditioning (RIC) regimen, is a promising treatment for advanced-stage MF/SS. We performed RIC-HSCT in nine patients with advanced MF/SS. With a median follow-up period of 954 days after HSCT, the estimated 3-year overall survival was 85.7% (95% confidence interval, 33.4-97.9%) with no non-relapse mortality. Five patients relapsed after RIC-HSCT; however, in four patients whose relapse was detected only from the skin, persistent complete response was achieved in one patient, and the disease was manageable in other three patients by the tapering of immunosuppressants and donor lymphocyte infusion, suggesting that graft-versus-lymphoma effect and 'down-staging' effect from advanced stage to early stage by HSCT improve the prognosis of advanced-stage MF/SS. These results suggest that RIC-HSCT is an effective treatment for advanced MF/SS.

  19. Influence of clinical and pathologic features on the pathologist's diagnosis of mycosis fungoides: a pilot study.

    PubMed

    Rovner, Rebecca; Smith, Hayden L; Katz, Peter J; Liu, Vincent

    2015-07-01

    Although clinicopathologic correlation is critical in the diagnosis of early mycosis fungoides (MF), how clinical information directly affects the pathologist's interpretation is unknown. This pilot study aimed to assess the influence of provided clinical information and specific histopathologic features on the histopathologic diagnosis of MF vs. its inflammatory simulants. A computerized survey recorded diagnostic impressions by 24 dermatopathologists of 30 hematoxylin-eosin stained images, including 15 MF images and 15 dermatitis images. Images were accompanied by concordant clinical descriptions (33%), no clinical information (33%) or discordant clinical descriptions (33%). Percentage of correctly classified MF histopathologic images for the three scenarios of concordant clinical information, no clinical information or discordant clinical information were 32% (kappa 0.19), 56% (kappa 0.12) and 16% (kappa 0.33), respectively. The percentage of correctly classified slides presented with no clinical information was different from the other two groups (p < 0.0001). Pautrier collections were most associated with correct classification. Clinical information may play a significant role in the histopathologic diagnosis of MF, although there may be some value in initial blinded histopathologic interpretation. Specific histopathologic features differ in relative importance in the diagnosis of MF.

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

    PubMed

    Ladrigan, Manasi Kadam; Poligone, Brian

    2014-12-01

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

  1. 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

  2. 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

  3. 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.

  4. Prognostic factors, prognostic indices and staging in mycosis fungoides and Sézary syndrome: where are we now?

    PubMed

    Scarisbrick, J J; Kim, Y H; Whittaker, S J; Wood, G S; Vermeer, M H; Prince, H M; Quaglino, P

    2014-06-01

    Mycosis fungoides is the most prevalent form of primary cutaneous T-cell lymphoma. Patients frequently present with early-stage disease typically associated with a favourable prognosis and survival of 10-35 years, but over 25% may progress to advanced disease with a median survival < 4 years, and just 13 months in those with nodal involvement. Sézary syndrome presents in advanced disease with erythroderma, blood involvement and lymphadenopathy. The Bunn and Lamberg staging system (1979) includes stages IA-IIA (early-stage disease) and IIB-IVB (advanced-stage disease) and provides prognostic information, but some patients with tumour-stage disease (IIB) have a worse prognosis than those with erythrodermic-stage (III). Conversely, patients with plaque-stage (IB) folliculotropic mycosis fungoides may have a worse outcome than those with tumour-stage (IIB). The more recent staging system of the European Organisation for the Research and Treatment of Cancer/International Society for Cutaneous Lymphoma has been designed to reflect tumour burden at different sites. However, this staging system has not been validated prospectively for prognosis. Furthermore, this staging system does not include a detailed measurement of skin tumour burden, as indicated by the modified skin weighted severity assessment tool. This assessment measures body surface area of disease and is weighted to record patch, plaque and tumour to produce a numerical value from 0·5 to 400 and is an established endpoint for clinical studies. Nor does this staging include clinicopathological features associated with a poor prognosis such as folliculotropism. Here we review the clinical, haematological, pathological and genotypic parameters outside the staging system, which may affect survival in mycosis fungoides and Sézary syndrome. Most studies are retrospective and single centre. The identification of poor prognostic factors may be used to develop a prognostic index to use alongside staging, which

  5. Follicular mucinosis and mycosis-fungoides-like drug eruption due to leuprolide acetate: a case report and review.

    PubMed

    Shalin, Sara C; Brantley, Julie; Diwan, A Hafeez

    2012-11-01

    Leuprolide acetate represents a gonadotropin-releasing hormone agonist, used as part of the treatment of prostate cancer. We report an unusual case of disseminated urticarial rash following leuprolide injection in a 67-year-old man that histopathologically and immunohistochemically resembled mycosis-fungoides, including the presence of follicular mucinosis and eosinophils in the follicles. This histopathologic pattern has not been previously described as a drug reaction pattern due to leuprolide, and it underscores the importance of correlation with the clinical impression to arrive at a correct diagnosis.

  6. Narrowband Ultraviolet B Phototherapy of Early Stage Mycosis Fungoides in Korean Patients

    PubMed Central

    Jang, Min Soo; Baek, Jae Woo; Park, Jong Bin; Kang, Dong Young; Kang, Jin Seuk; Suh, Kee Suck

    2011-01-01

    Background Narrowband UVB (NBUVB) is currently used to treat early mycosis fungoides (MF). There are a number of reports on the efficacy and safety of NBUVB in Caucasians, but little data is available for Asians. Objective This study was designed to evaluate the effectiveness and safety of NBUVB for early stage MF in Korean patients. Methods We enrolled 14 patients (12 men, 2 women; age range, 10~64 years) with clinically and histologically proven MF. Three patients were stage IA, and the others were stage IB. The patients received NBUVB phototherapy three times a week. The starting dose was 70% of the minimal erythema dose and was increased in 20 percent increments if the previous treatment did not cause erythema. Clinical response, total number of treatments, total cumulative dose, duration of remission and side effects were investigated. Results Eleven of 14 patients (78.6%) achieved complete remission within a mean of 15.36±5.71 weeks (range, 5~27 weeks), 31.0±7.4 treatments (range, 16~39 treatments) and a mean cumulative UVB dose of 31.31±12.16 J/cm2 (range, 11.4~46.8 J/cm2). Three of the 14 patients (21.4%) achieved a partial remission. After discontinuation of treatment, 6 of 11 patients (54.5%) with complete remission relapsed after a mean of 8.5±4.09 months. No serious adverse effects were observed except for hyperpigmentation (7/14, 50%). Conclusion Our data suggest that NBUVB therapy is safe and effective for the treatment of early stage MF in Korean patients. PMID:22148015

  7. Lymphomatoid papulosis in association with mycosis fungoides: a study of 15 cases.

    PubMed

    Basarab, T; Fraser-Andrews, E A; Orchard, G; Whittaker, S; Russel-Jones, R

    1998-10-01

    We report clinical findings in 15 patients with lymphomatoid papulosis (LyP) associated with mycosis fungoides (MF). LyP either preceded (n = 4), followed (n = 5) or occurred concurrently with the MF lesions (n = 6). Twenty-eight LyP lesions were classified histologically and analysed further with immunostaining for CD3 and CD30. Five biopsies contained a predominance of type A cells, six biopsies contained a predominance of type B cells. and six were mixed (A + B). However, 11 biopsies contained a population of atypical mononuclear cells with large hyperchromatic nuclei that we have termed indeterminate cells. These cells contained a thin rim of eosinophilic cytoplasm and showed strong CD30 but absent, faint or normal CD3 staining. In seven biopsies from five separate patients these cells represented the predominant cell type and we have termed this the pleomorphic variant of LyP. Analysis of T-cell receptor genes using Southern blot analysis and polymerase chain reaction/single strand conformational polymorphism analysis identified a T-cell clone in six of 16 LyP lesions and nine of 16 MF lesions. In the three patients who had clones in both types of skin lesions, the clones were identical. Only two of 10 blood samples, both of which were from the same patient, had a T-cell clone and none of two lymph nodes showed evidence of a clonal population. To date all patients are alive with a median follow-up of 15 years from the onset of the first lesion. One patient has developed Lin anaplastic large cell lymphoma of the nasopharynx. These data augment the current literature on the association of LyP and MF and suggest that the

  8. 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

  9. Oligonucleotide array-CGH identifies genomic subgroups and prognostic markers for tumor stage mycosis fungoides.

    PubMed

    Salgado, Rocío; Servitje, Octavio; Gallardo, Fernando; Vermeer, Maarten H; Ortiz-Romero, Pablo L; Karpova, Maria B; Zipser, Marie C; Muniesa, Cristina; García-Muret, María P; Estrach, Teresa; Salido, Marta; Sánchez-Schmidt, Júlia; Herrera, Marta; Romagosa, Vicenç; Suela, Javier; Ferreira, Bibiana I; Cigudosa, Juan C; Barranco, Carlos; Serrano, Sergio; Dummer, Reinhard; Tensen, Cornelis P; Solé, Francesc; Pujol, Ramon M; Espinet, Blanca

    2010-04-01

    Mycosis fungoide (MF) patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present European Organization for Research and Treatment of Cancer (EORTC) multicenter study, the genomic profile of 41 skin biopsies from tumor stage MF (MFt) was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter, and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2, and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21, and 10q26qter, were defined as prognostic markers showing a significant correlation with overall survival (OS) (P=0.042, 0.017, and 0.022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (>5 DNA aberrations), showing that the genomic unstable group had a shorter OS (P=0.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B, and MTAP) and 10q26qter (MGMT and EBF3) may have an important role in prognosis. In addition, we describe the MFt genomic instability profile, which, to our knowledge, has not been reported earlier.

  10. Mycosis fungoides with large cell transformation: clinicopathological features and prognostic factors

    PubMed Central

    Pulitzer, Melissa; Myskowski, Patricia L.; Horwitz, Steven M.; Querfeld, Christiane; Connolly, Brian; Li, Janet; Murali, Rajmohan

    2016-01-01

    Summary Large cell transformation of mycosis fungoides (MF-LCT) occurs in 20–50% of advanced MF, and is generally associated with poor prognosis, although some patients have indolent disease. We sought to identify clinicopathological prognostic factors in a large number of patients with MF-LCT. We identified patients with MF-LCT treated between 1991 and 2012 at a referral centre for cutaneous lymphoma. Clinical and pathological records, and histopathological slides were reviewed. Associations of clinicopathological variables with disease-specific survival were analysed. In 51 patients with MF-LCT, factors significantly associated with shorter survival were: age >60 years (25 versus 61 months, p = 0.01), stage III/IV (25 versus 44 months, p = 0.049), high serum lactate dehydrogenase (LDH; 24 versus 53 months, p = 0.007), absent papillary dermal involvement (8 versus 30 months, p = 0.008); follicular mucin at transformation (24 versus 42 months, p = 0.007); and the absence of fibrosis at transformation (21 versus 42 months, p = 0.03). Patients presenting with transformation at diagnosis had better survival than those who started with a small cell phenotype (p = 0.02). Age >60 years was independently associated with poorer survival (HR 5.61, 95%CI 1.17–26.8, p = 0.03), and the presence of fibrosis at transformation was independently associated with improved survival (HR 0.30, 95%CI 0.09–0.97, p = 0.045). In patients with MF-LCT, clinical features (age, stage, serum LDH) are important in assessing prognosis. Additional clinical and pathological features identified in this study may also assist in prognostic stratification. Studies of larger cohorts should be performed to validate the prognostic significance of these features. PMID:25393251

  11. 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.

  12. Evaluation of neutrophil-lymphocyte ratio in patients with early-stage mycosis fungoides.

    PubMed

    Eren, Rafet; Nizam, Nihan; Doğu, Mehmet Hilmi; Mercan, Sevgi; Erdemir, Aslı Vefa Turgut; Suyanı, Elif

    2016-10-01

    Neutrophil-lymphocyte ratio (NLR), an indicator of inflammation, has been lately demonstrated as a prognostic factor and an indicator of disease activity in various diseases. However, the effects of NLR have not been investigated in mycosis fungoides (MF) patients yet. The aim of this study is to investigate the relationship between the NLR and treatment demand (systemic PUVA and/or chemotherapy), time to treatment, progression in stage, and time to progression in stage in MF patients. The data of 117 patients, who were followed with the diagnosis of MF at the Department of Dermatology in Istanbul Training and Research Hospital between April 2006 and January 2016, were analyzed retrospectively. The cutoff score for NLR was determined as 2 according to the median NLR level which was 1.96. At the time of diagnosis, the median age of patients was 54 years (range, 21-90) with 62 (53 %) female and 55 (47 %) male. Seventy-seven (65.8 %) patients required treatment during follow-up. Sixty-three (53.8 %) patients showed progression in disease stage. There was no significant difference in treatment demand, time to treatment, progression in stage, and time to progression in stage in patients with a NLR ≥ 2 and NLR < 2 (p = 0.331, 0.987, 0.065, and 0.119, respectively). It seems that there is no association between the NLR and treatment demand, time to treatment, progression in stage, and time to progression in stage in MF patients.

  13. Lymph node involvement by mycosis fungoides and Sézary syndrome mimicking angioimmunoblastic T-cell lymphoma.

    PubMed

    LeBlanc, Robert E; Lefterova, Martina I; Suarez, Carlos J; Tavallaee, Mahkam; Kim, Youn H; Schrijver, Iris; Kim, Jinah; Gratzinger, Dita

    2015-09-01

    Clinical management of cutaneous T-cell lymphoma (CTCL) and angioimmunoblastic T-cell lymphoma (AITL) differs markedly. Diagnostic distinction is critical. Herein, we describe a series of 4 patients with clinically, molecularly, and histopathologically annotated mycosis fungoides or Sézary syndrome whose nodal disease mimicked AITL. The patients otherwise exhibited classic clinical manifestations of mycosis fungoides/Sézary syndrome preceding the onset of lymphadenopathy by 1 to 5 years. Skin biopsies revealed epidermotropic infiltrates characteristic of CTCL. Lymph node biopsies revealed dense CD4+ T-cell infiltrates that coexpressed follicular helper T-cell markers and were accompanied by proliferations of high endothelial venules and arborizing CD21+ follicular dendritic cell networks. Two patients had T-cell receptor gene rearrangement studies performed on their skin, lymph node, and peripheral blood demonstrating identical polymerase chain reaction clones in all 3 tissues. A small secondary clonal B-cell population was present in 1 patient that mimicked the B-cell proliferations known to accompany AITL and persisted on successive nodal biopsies over several years. This latter phenomenon has not previously been described in CTCL. The potential for patients to be misdiagnosed with AITL for lack of consideration of advanced-stage CTCL with nodal involvement underscores the necessity of information sharing among the various pathologists and clinicians involved in the care of each patient.

  14. Allelotyping in mycosis fungoides and Sézary syndrome: common regions of allelic loss identified on 9p, 10q, and 17p.

    PubMed

    Scarisbrick, J J; Woolford, A J; Russell-Jones, R; Whittaker, S J

    2001-09-01

    Allelotyping studies have been extensively used in a wide variety of malignancies to define chromosomal regions of allelic loss and sites of putative tumor suppressor genes; however, until now this technique has not been used in cutaneous lymphoma. We have analyzed 51 samples from patients with mycosis fungoides and 15 with Sézary syndrome using methods to detect loss of heterozygosity. Micro satellite markers were selected on 15 chromosomal arms because of their proximity to either known tumor suppressor genes or chromosomal abnormalities identified in previous cytogenetic studies in cutaneous lymphoma. Allelic loss was present in 45% of patients with mycosis fungoides and 67% with Sézary syndrome. Loss of heterozygosity was found in over 10% of patients with mycosis fungoides on 9p, 10q, 1p, and 17p and was present in 37% with early stage (T1 and T2) and 57% with advanced disease (T3 and T4). Allelic loss on 1p and 9p were found in all stages of mycosis fungoides, whereas losses on 17p and 10q were limited to advanced disease. In Sézary syndrome high rates of loss of heterozygosity were detected on 9p (46%) and 17p (42%) with lower rates on 2p (12%), 6q (7%), and 10q (12%). There was no significant difference in the age at diagnosis or number of treatments received by those with loss of heterozygosity and those without, suggesting that increasing age and multiple treatments do not predispose to allelic loss. These results provide the basis for further studies defining more accurately chromosomal regions of deletions and candidate tumor suppressor genes involved in mycosis fungoides and Sézary syndrome.

  15. Occupational risk factors for mycosis fungoides: a European multicenter case-control study.

    PubMed

    Morales-Suárez-Varela, Maria M; Olsen, Jorn; Johansen, Preben; Kaerlev, Linda; Guénel, Pascal; Arveux, Patrick; Wingren, Gun; Hardell, Lennart; Ahrens, Wolfgang; Stang, Andreas; Llopis, Agustin; Merletti, Franco; Aurrekoetxea, Juan Jose; Masala, Giovanna

    2004-03-01

    Mycosis fungoides (MF) is a rare disease with an unknown etiology. Its distribution suggests that occupational exposures may play a role. In the present study, we searched for occupational factors associated with MF. A European multicenter case-control study on seven rare cancers, including MF, was conducted from 1995 to 1997. Patients between 35 and 69 years of age diagnosed with MF (n = 134) were identified and their diagnoses were checked by a reference pathologist who classified 83 cases as definitive, 35 cases as possible, and 16 cases as not histologically verified. Of the 118 histologically verified cases, 104 were interviewed, of which 76 were definitive cases. As controls, we selected population controls and colon cancer controls to serve all seven case groups. Altogether, 833 colon cancer controls and 2071 population controls were interviewed. The response rate was 91.5% for cases (76 of the 83 definitive cases), and 66.6% for controls. A high risk of MF for men was observed in the industries of other non-metallic mineral products (Odds Ratio [OR] 5.3, 95% confidence interval [CI] = 1.7-16.2) and of wholesale trade (OR 3.6, 95% CI = 1.3-10.5). A high risk was found for female employees in the sector of pulp paper manufacture (OR 14.4, 95% CI = 2.2-95.1). The male occupations with the highest risks were glass formers, potters, and ceramics workers (OR 17.9, 95% CI = 5.4-59.4) and technical salesmen (OR 8.6, 95% CI = 2.4-30.8). For women, the occupations associated with the highest risks were government executives (OR 4.8, 95% CI = 1.0-22.6) and railway and road vehicles loaders (OR 3.9, 95% CI = 1.0-14.0). The results suggest that some occupational factors are associated with MF. Working as glass formers, pottery, and ceramics workers carried the highest risk, and these findings deserve further attention and replication. Females working in the paper and pulp industries may also be exposed to carcinogens of relevance to MF.

  16. Total body-surface area as a new prognostic variable in mycosis fungoides and Sézary syndrome.

    PubMed

    Novelli, Silvana; García-Muret, Pilar; Mozos, Anna; Sierra, Jorge; Briones, Javier

    2016-05-01

    Mycosis fungoides and Sézary syndrome (MF/SS) are the most common forms of primary cutaneous T cell lymphomas. We analyzed the applicability of the cutaneous lymphoma international prognostic index (CLIPi) in MF/SS. We introduced the total body-surface area affected (TBSA) and the type of skin lesions at diagnosis as prognostic variables. The overall survival (OS) at median time of follow up (96 months) was 75.6% (CI 95%, 62.0-98.5%). In the univariate analysis, age>60 years, advanced disease, type of skin lesions and TBSA>50 showed poorer OS (p<0.05). In the multivariate analysis there was a significant increased relative risk of death in those patients>60 years, with advanced disease and TBSA>50% (p<0.05). TBSA identified a group of poor prognosis patients with advanced MF/SS that may benefit from novel systemic therapies.

  17. CD3 and CD20 Coexpression in a Case of Canine Cutaneous Epitheliotropic T-Cell Lymphoma (Mycosis Fungoides).

    PubMed

    Brachelente, C; Affolter, V K; Fondati, A; Porcellato, I; Sforna, M; Lepri, E; Mechelli, L; Bongiovanni, L

    2016-05-01

    A 14-year-old female spayed Dachshund was presented with generalized scaling, erythema, pruritus, poor quality of hair coat, and progressive weight loss. Cutaneous epitheliotropic T-cell lymphoma (CETCL) was suspected. Skin biopsies were suggestive of CETCL. However, immunohistochemistry revealed the presence of numerous CD20+ and CD3+ cells. Clonality assay demonstrated a clonal T-cell receptor gamma rearrangement and a polyclonal IgH gene rearrangement. Double-label immunofluorescence confirmed coexpression of CD3 and CD20 by neoplastic cells. By double immunohistochemistry, neoplastic cells were CD3+ and PAX5-. The results are compatible with a CD3+, CD20+ CETCL. Coexpression of CD20 and CD3 has been recognized in peripheral T-cell lymphomas. Although documented in human CETCL, it has not been reported in canine CETCL. The pathogenetic basis of CD20 expression in mycosis fungoides is explored. PMID:26354309

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-06-01

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

  20. Mycosis Fungoides Associated with Kaposi's Sarcoma, T-cell Rich B-cell Lymphoma, and T-cell Lymphoma with Angioimmunoblastic Features.

    PubMed

    Samuelov, Liat; Gat, Andrea; Bergman, Reuven; Sprecher, Eli; Goldberg, Ilan

    2016-08-01

    A patient with mycosis fungoides (MF), Kaposi's sarcoma, T-cell rich B-cell lymphoma, and T-cell lymphoma with angioimmunoblastic features is described. The appearance of multiple malignancies in this patient may have been caused by previous exposure to radiation in the Chernobyl accident and/or systemic chemotherapy for the initial T-cell rich B-cell lymphoma which he underwent. PMID:27663924

  1. 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.

  2. Autologous peripheral blood stem cell transplantation in tumor-stage mycosis fungoides: predictors of disease-free survival.

    PubMed

    Russell-Jones, R; Child, F; Olavarria, E; Whittaker, S; Spittle, M; Apperley, J

    2001-09-01

    Nine patients with mycosis fungoides (age range 27-67) underwent autologous peripheral blood stem cell transplantation (PBSCT). All patients had tumor-stage disease, and four had lymph node involvement. Eight patients exhibited a peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells was achieved with etoposide and G-CSF. Harvested cells were positively selected for CD34. After negative selection for CD4 and CD8, only two samples became PCR negative. Conditioning prior to reinfusion of stem cells was achieved with various combinations of total skin electron beam (TSEB), total body irradiation (TBI), and chemotherapy, depending upon the patient's prior exposure to radiotherapy. One patient failed to engraft and died of candidal septicemia 15 days posttransplant. The other eight patients achieved complete remission, but this was short-lived in four (median disease-free survival [DFS] = 2 months) and prolonged in three (median DFS 11 months). Those with a short DFS were distinguished by rapid tumor onset prior to transplant but not by stage at transplant. Loss of a detectable T cell clone after manipulation of the harvest did not discriminate between the two groups, but rapid relapsers had been subjected to a greater degree of T cell depletion, possibly indicating a compromised cytotoxic response post-PBSCT. The median survival of the cohort is four years from tumor onset, 15 months from PBSCT, and 27 months from the date a peripheral blood clone was first detected in the presence of tumor-stage disease. Rapid relapse was associated with poor overall survival. Our data demonstrate the value of PBSCT for inducing remission in tumor-stage mycosis fungoides. Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an earlier stage in the disease process, preferably before a T cell clone is detectable in the peripheral blood. Alternatively T cell

  3. 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

  4. 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

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

    PubMed

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

    2015-02-01

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

  6. Evolving insights in the pathogenesis and therapy of cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome).

    PubMed

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

    2011-10-01

    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

  7. The Dilemma of Coexisting Nevoid Hyperkeratosis of the Nipple and Areola in Mycosis Fungoides: A Report of Three Cases

    PubMed Central

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

    2015-01-01

    Nevoid hyperkeratosis of the nipple and areola (NHNA) is a rare clinicopathological entity showing persistent and strictly localized hyperkeratotic lesions of the nipple, areola or both with unknown etiopathogenesis. A similar clinical appearance may also be seen in different diseases with specific histopathological features. There are a few anecdotal reports on the association of NHNA with mycosis fungoides (MF), but they do not describe a uniform condition. In this report, we present 3 patients with hyperkeratotic lesions of the nipple and areola associated with MF but showing different histopathological features. We also review similar cases in the literature and discuss possibilities concerning this association. Two of our cases represent the association between MF and NHNA without histopathological features of MF on the nipple-areola complex. The other case represents hyperkeratosis of the nipple and areola with specific histological and immunohistochemical features of MF. Hence, we would like to hypothesize that MF may involve the nipple and areola and have an appearance similar to NHNA. Intriguingly, however, NHNA may occasionally also be seen in association with MF. However, this peculiar association requires further explanation. PMID:27047936

  8. The Dilemma of Coexisting Nevoid Hyperkeratosis of the Nipple and Areola in Mycosis Fungoides: A Report of Three Cases.

    PubMed

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

    2015-01-01

    Nevoid hyperkeratosis of the nipple and areola (NHNA) is a rare clinicopathological entity showing persistent and strictly localized hyperkeratotic lesions of the nipple, areola or both with unknown etiopathogenesis. A similar clinical appearance may also be seen in different diseases with specific histopathological features. There are a few anecdotal reports on the association of NHNA with mycosis fungoides (MF), but they do not describe a uniform condition. In this report, we present 3 patients with hyperkeratotic lesions of the nipple and areola associated with MF but showing different histopathological features. We also review similar cases in the literature and discuss possibilities concerning this association. Two of our cases represent the association between MF and NHNA without histopathological features of MF on the nipple-areola complex. The other case represents hyperkeratosis of the nipple and areola with specific histological and immunohistochemical features of MF. Hence, we would like to hypothesize that MF may involve the nipple and areola and have an appearance similar to NHNA. Intriguingly, however, NHNA may occasionally also be seen in association with MF. However, this peculiar association requires further explanation. PMID:27047936

  9. Notch1 Pathway Activation Results from the Epigenetic Abrogation of Notch-Related MicroRNAs in Mycosis Fungoides.

    PubMed

    Gallardo, Fernando; Sandoval, Juan; Díaz-Lagares, Angel; Garcia, Ricard; D'Altri, Teresa; González, Jessica; Alegre, Victor; Servitje, Octavio; Crujeiras, Ana-Belén; Stefánsson, Ólafur-Andri; Espinet, Blanca; Hernández, Maria-Inmaculada; Bellosillo, Beatriz; Esteller, Manel; Pujol, Ramon-Maria; Bigas, Anna; Espinosa, Lluis

    2015-12-01

    Notch is a family of transmembrane receptors that participate in the regulation of cell differentiation, proliferation, and stemness. Notch pathway activation has also been found associated with different human cancers including primary cutaneous T-cell lymphomas (CTCL). The elucidation of the mechanisms driving Notch activation in these particular diseases has remained elusive. Here we studied the possibility that DNA methylation at Notch pathway gene promoters and/or deregulation of Notch-associated microRNAs contribute to activate Notch in mycosis fungoides (MF). By genome-wide DNA methylation analysis, we failed to detect any consistent methylation at the Notch1, the Notch-ligand Jagged1, or the Notch-target Hes1 gene promoters, but found a significant methylation of the Notch-related microRNAs, in particular miR-200c and miR-124. Downregulation of miR-200c is associated with overexpression of Jagged1, concomitant to Notch1 activation. CTCL cell lines were infected with lentiviral vector encoding for miR-200c and ectopic expression of miR-200c in CTCL lines resulted in Jagged1 protein downregulation associated with a reduction in the levels of active Notch1. Our study deciphers an epigenetic mechanism regulating the Notch pathway in (MF) that might contribute to the future design of more specific therapeutic strategies. PMID:26302069

  10. EBV+ cutaneous B-cell lymphoproliferation of the leg in an elderly patient with mycosis fungoides and methotrexate treatment.

    PubMed

    Rausch, Thierry; Cairoli, Anne; Benhattar, Jean; Spring, Philipp; Hohl, Daniel; de Leval, Laurence

    2013-01-01

    A 77-year-old man with a 5-year history of mycosis fungoides (MF) who had received several lines of therapy, including intravenous courses of Methotrexate (MTX) for the past 2 years, went on to develop several ulcerated cutaneous nodules on the left leg. Biopsy revealed diffuse sheets of EBV-positive large B cells (CD20+ CD30 ± IgM Lambda), with an angiocentric distribution and a monoclonal IGH gene rearrangement. Although the pathological features were diagnostic for an EBV-positive diffuse large B-cell lymphoma (DLBCL), several possibilities could be considered for assignment to a specific entity: EBV-positive DLBCL of the elderly, methotrexate-induced lymphoproliferative disorder (LPD), lymphomatoid granulomatosis, or the more recently described EBV-positive mucocutaneous ulcer. The development of EBV+ lymphoproliferations has been reported in two other patients with MF under MTX, and occurred as skin lesions of the leg in one of these and in the current case, which may question the relatedness to primary cutaneous DLCBL, leg-type. PMID:23031074

  11. 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

  12. 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

  13. 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

  14. 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

  15. Evaluation of T-cell receptor gene rearrangements in patients with recurrent patch/plaque (T2) CTCL (mycosis fungoides).

    PubMed Central

    Thayu, M.; Tallini, G.; Glusac, E. J.; Kacinski, B. M.; Wilson, L. D.

    1999-01-01

    Cutaneous T-cell lymphoma is typically a clonal neoplasm of epidermotropic CD4+ T-lymphocytes that includes the entity mycosis fungoides (MF). After identification of patients with recurrent MF treated with total skin electron beam therapy (TSEBT) at the Yale University School of Medicine, this study attempted to compare T-cell receptor (TCR) gamma gene rearrangements via polymerase chain reaction (PCR) in both original and recurrent skin biopsies from these patients. Between 1974 and 1996, a total of 95 T2 MF patients were treated with TSEB, and four of these were identified for the study. Slides and tissue samples of both primary and recurrent skin biopsies for each patient were confirmed as being consistent with ME DNA for PCR was isolated from paraffin-embedded tissue samples. Using consensus primers that hybridize with conserved regions of the TCR gene, these regions of the genome were amplified. The PCR products were then analyzed by acrylamide gel electrophoresis. Of the primary and recurrent samples from four patients with a median disease-free interval (DFI) of 1222 days, only two showed evidence of a dominant TCR clone. A number of factors, including lack of sequence homology between the primers and the gene segments, the existence of multiple neoplastic cell lines, DNA degradation in the archival samples, and the presence of reactive as well as malignant lymphocytes, may have prevented the detection of dominant TCR rearranged clones in the samples. Despite the results of this study, TCR analysis via PCR and gel electrophoresis continues to be of utility in the evaluation of patients with MF when used in conjunction with other diagnostic modalities and in cases with nonspecific clinical, histopathological, and immunophenotyping findings. Images Figure 1 PMID:11138932

  16. Recurring structural chromosome abnormalities in peripheral blood lymphocytes of patients with mycosis fungoides/Sézary syndrome.

    PubMed

    Thangavelu, M; Finn, W G; Yelavarthi, K K; Roenigk, H H; Samuelson, E; Peterson, L; Kuzel, T M; Rosen, S T

    1997-05-01

    Cytogenetic analysis was performed on peripheral blood lymphocyte cultures from 19 patients with mycosis fungoides (MF)/Sézary syndrome (SS) stimulated with either phytohemagglutinin, a conventional mitogen, or a combination of interleukin-2 (IL-2) plus IL-7. The use of both PHA-stimulated and IL-2 plus IL-7-stimulated cultures enhanced the ability to identify clonal abnormalities. Clonal abnormalities were observed in 11 patients (53%) including one with monosomy for the sex chromosome as the sole abnormality. Five of the 11 patients with clonal abnormalities had normal peripheral white blood cell counts, indicating detectability of clones in the absence of frankly leukemic disease. The presence of clonal abnormalities correlated with advanced stage disease and a significantly reduced survival duration from the time of cytogenetic studies. Clonal abnormalities involving chromosomes 1 and 8 were observed in six cases. In five cases with aberrations of chromosome 1, loss of material involved the region between 1p22 and 1p36. In an additional case, a reciprocal translocation involving 1p33 was observed. Clonal abnormalities involving chromosomes 10 and 17 were observed in 5 cases, clonal abnormalities involving chromosome 2 in 4 cases, and clonal abnormalities involving chromosomes 4, 5, 6, 9, 13, 15, 19, and 20 in 3 cases. In 2 cases a der(8)t(8;17)(p11;q11) was observed. Regions of the genome that encode T-cell receptors were not involved in abnormalities. The region between 1p22 and 1p36 is identified as a region of the genome that requires detailed analysis toward the identification of potential gene(s) involved in the process of malignant transformation and/or progression in MF/SS.

  17. Shared clonality in distinctive lesions of lymphomatoid papulosis and mycosis fungoides occurring in the same patients suggests a common origin.

    PubMed

    de la Garza Bravo, Maria M; Patel, Keyur P; Loghavi, Sanam; Curry, Jonathan L; Torres Cabala, Carlos A; Cason, Ronald C; Gangar, Pamela; Prieto, Victor G; Medeiros, L Jeffrey; Duvic, Madeleine; Tetzlaff, Michael T

    2015-04-01

    Lymphomatoid papulosis (LyP) lies within the spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Approximately 10% to 15% of patients with LyP develop other lymphomas, most commonly mycosis fungoides (MF), suggesting a biological relationship between these distinctive diseases. Here, we describe the clinical and histopathologic features of 11 patients who had both LyP and MF, including a total of 30 biopsy specimens (14 LyP and 16 MF). Clinically, LyP lesions were characterized by clustered papules undergoing spontaneous regression and were classified as type A (n = 11), type C (n = 2), or type D (n = 1). All cases of MF were characterized clinically by patch/plaque disease, were stage I or II at the time of diagnosis, and consisted of a CD4-predominant epidermotropic T-cell infiltrate. We used polymerase chain reaction-based methods to assess the TCR-β chain (TCRB) and TCR-γ chain (TCRG) in both LyP and MF lesions of all patients. Monoclonal TCR gene rearrangements were detected in 13 LyP lesions from 10 of 11 patients and in 14 MF lesions from 10 of 11 patients. All 10 patients in whom their skin lesions carried monoclonal TCR gene rearrangements exhibited overlapping clones in both their LyP and MF lesions; additional non-overlapping clones were identified in 3 LyP lesions from 2 patients and 1 MF lesion from another patient. The demonstration of shared monoclonal T-cell receptor gene rearrangements in LyP and MF lesions in almost all patients suggests a common origin between these distinctive clinicopathological diseases.

  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 possible interaction between periostin expressed by cancer stroma and tumor-associated macrophages in developing mycosis fungoides.

    PubMed

    Furudate, Sadanori; Fujimura, Taku; Kakizaki, Aya; Kambayashi, Yumi; Asano, Masayuki; Watabe, Akiko; Aiba, Setsuya

    2016-02-01

    Mycosis fungoides (MF) starts as an indolent disease, progresses from a patch stage to confluent plaques and ultimately develops skin tumors. Tumor-associated macrophages (TAMs) play roles in maintaining the tumor microenvironment in MF. The purpose of this study was to elucidate the involvement of TAMs in the lesional skin of different stages of MF. First, we immunohistologically examined the percentage of CD163+ macrophages and CD206+ cells, as well as the levels of periostin and IL-4 in cancer stroma. The percentage of CD206+ cells increased in parallel with tumor progression, while there was no significant difference in the percentage of CD163+ cells. Periostin was prominent in the stromal area at the patch and plaque stages but decreased at the tumor stage. In contrast, IL-4 was prominently stained at both plaque and tumor stages. To further elucidate the molecular mechanisms of the effects of these stromal factors on TAMs, we examined their effects on mRNA expression in monocyte-derived macrophages in vitro. Based on microarray analysis and gene ontology, we examined a series of chemokines and MMPs whose expression was strongly connected with periostin stimulation. The DNA microarray results were verified in M2 macrophages using real-time PCR. We further examined the mRNA expression of these chemokines and MMPs in the presence of periostin and IL-4 to simulate the advanced stages of MF and validated their protein expression by ELISA. Our present report suggests possible roles of periostin on TAMs in establishing the tumor microenvironment in MF. PMID:26441016

  20. Analysis of beta, gamma, and delta T-cell receptor genes in mycosis fungoides and Sezary syndrome.

    PubMed

    Whittaker, S J; Smith, N P; Jones, R R; Luzzatto, L

    1991-10-01

    The authors have analyzed the configuration of immunoglobulin (Ig) and beta, gamma and delta T-cell receptor (TCR) genes in DNA extracted from skin, lymph nodes, and peripheral blood mononuclear cells obtained from 41 patients with mycosis fungoides (MF), 14 patients with Sezary syndrome, and 13 patients with benign inflammatory dermatoses. No discrete rearranged bands (DRB) were detected in patients with inflammatory dermatoses. In tissue DNA from 19 patients with MF DRB were detected with beta and gamma, but not delta TCR probes. Only one patient with MF had a rearrangement of gamma and delta with germ line beta TCR genes. In 13 patients multiple biopsies were analyzed and DRB, when present, were identical in different lesions from individual patients. In three patients analysis of DNA from dermatopathic lymph nodes did not reveal DRB. Analysis of peripheral blood DNA from 24 patients revealed a discrete rearrangement of the gamma TCR gene in four patients and both beta and gamma genes in four additional patients. In MF DRB were detected more frequently with advancing stage of disease in tissues (P less than 0.01) but not in peripheral blood (P equals 0.36). Of 14 patients with Sezary syndrome, eight had DRB in peripheral blood DNA with both beta and gamma probes and in three of these patients identical DRB were also detected in DNA from skin biopsy samples. In contrast, DRB were not detected in the peripheral blood of the other six patients. In both MF and Sezary syndrome there was no restricted usage of particular V gamma genes. These results indicate that in MF (1) T-cell clones can be detected in skin biopsy specimens from the majority of patients with early stage disease, (2) gamma delta T-cell clones are only rarely found, and (3) TCR gene analysis can detect T-cell clones in the peripheral blood with a greater degree of specificity than conventional light microscopic study. In Sezary syndrome these studies also suggest that a subset of patients have a

  1. T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a ligand for CD28.

    PubMed

    Nickoloff, B J; Nestle, F O; Zheng, X G; Turka, L A

    1994-05-01

    The activation of T cells requires two distinct signals. One signal involves interaction of the antigen-specific T-cell receptor with major histocompatibility complex molecules plus antigenic peptide; a second signal, which is antigen nonspecific, is the interaction of CD28 with its natural ligands B7-1 and B7-2/B70. CD28 is expressed on 80% of T cells, is upregulated after activation, and binds to B7 gene-family members, found on antigen-presenting cells. Because of our interest in the immunologic basis of benign and malignant T-cell-mediated disorders of the skin, we investigated the cellular distribution of CD28 and B7 family members in lesions of psoriasis and mycosis fungoides. By immunostaining cryostat sections of skin, CD28 was found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. Surprisingly, B7-1 was also found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. B7-1 expression was confirmed on CD3+ T lymphocytes using flow cytometry of single cell suspensions of fresh, unfixed psoriatic lesional tissue. To exclude the possibility that this result was caused by a second reagent contaminating the monoclonal antibody (MoAb) preparation, two different lots were used, and the MoAb was absorbed onto Chinese hamster ovary (CHO) transfectants expressing B7-1, or vector-only transfected CHO cells. These procedures confirmed that a B7-1-like epitope was being recognized on psoriatic lesional T cells. In contrast to B7-1 expression on lymphocytes, B7-3, as defined by anti-BB-1 MoAb reactivity, was found primarily on epidermal keratinocytes in both skin diseases and was not found on T cells. These results indicate that within two common skin disorders, lesional T cells accumulate in the dermis and epidermis, which express B7-1. Such expression may permit self-costimulation involving the CD28-mediated activation pathway, and thereby contribute to the ongoing T

  2. T-cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement.

    PubMed

    Olavarria, E; Child, F; Woolford, A; Whittaker, S J; Davis, J G; McDonald, C; Chilcott, S; Spittle, M; Grieve, R J; Stewart, S; Apperley, J F; Russell-Jones, R

    2001-09-01

    Nine patients with tumour stage mycosis fungoides (MF) have been entered into a pilot study of T-cell depletion and autologous stem cell transplantation (SCT). Eight patients had detectable rearrangements of the T-cell receptor (TCR) gamma-gene demonstrated by polymerase chain reaction (PCR)/single-stranded conformation polymorphism (SSCP) in the peripheral blood. The median age was 47 years and the median duration of disease before SCT was 61 months; Peripheral blood progenitor cells were mobilized using high-dose etoposide (1.6 g/m2) and granulocyte colony-stimulating factor (G-CSF). The apheresis products underwent rigorous T-cell depletion with immunomagnetic methods. Double CD34-positive and CD4/CD8-negative selection achieved a median reduction of 3.89 log of T cells. All nine patients have been transplanted. Conditioning included carmustine (BCNU), etoposide and melphalan (BEM) in seven patients and total body irradiation plus etoposide or melphalan in two. Eight patients engrafted promptly and one patient died of septicaemia. All survivors entered complete remission. Seven patients have relapsed at a median of 7 months (2-14) post SCT. However, most patients have relapsed into a less aggressive stage, which has responded to conventional therapy. Four out of seven evaluable patients had detectable TCR rearrangements in the T-cell depleted graft. A T-cell clone was also detected in the peripheral blood before relapse in four cases. Autologous SCT is feasible, safe and can result in complete remission in a significant proportion of patients with tumour stage mycosis fungoides. Despite a short relapse-free survival, most patients achieved good disease control at the time of relapse.

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

    PubMed

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

    2014-10-01

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

  4. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC).

    PubMed

    Olsen, Elise; Vonderheid, Eric; Pimpinelli, Nicola; Willemze, Rein; Kim, Youn; Knobler, Robert; Zackheim, Herschel; Duvic, Madeleine; Estrach, Teresa; Lamberg, Stanford; Wood, Gary; Dummer, Reinhard; Ranki, Annamari; Burg, Gunter; Heald, Peter; Pittelkow, Mark; Bernengo, Maria-Grazia; Sterry, Wolfram; Laroche, Liliane; Trautinger, Franz; Whittaker, Sean

    2007-09-15

    The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions.

  5. Efficacy and tolerability of currently available therapies for the mycosis fungoides and Sezary syndrome variants of cutaneous T-cell lymphoma.

    PubMed

    Whittaker, Sean J; Foss, Francine M

    2007-04-01

    Primary cutaneous T-cell lymphomas are a heterogenous group of non-Hodgkin lymphomas. The characteristic clinicopathologic and immunophenotypic features and prognoses of the various cutaneous lymphomas have been recently described by the World Health Organization and European Organization for Research and Treatment of Cancer. Cutaneous T-cell lymphoma variants include mycosis fungoides and Sezary syndrome, which are generally associated, respectively, with indolent and aggressive clinical courses and are the subject of this review. Currently utilized treatments for cutaneous T-cell lymphoma include skin-directed therapies (topical agents such as corticosteroids, mechlorethamine, carmustine, and retinoids, phototherapy, superficial radiotherapy, and total skin electron beam therapy), systemic therapies (photophoresis, retinoids, denileukin diftitox, interferons, and chemotherapy), and stem cell transplantation (autologous and allogeneic). This review will describe recent advances in our understanding of the biology (immunologic, cytogenetic, and genetic) of cutaneous T-cell lymphomas and discuss the efficacy and tolerability of the current therapeutic options for cutaneous T-cell lymphomas. Disease progression in over 20% of patients with early stages of disease and the current lack of a definitive treatment which produces durable responses in advanced stages of disease indicates a critical unmet need in CTCL. New insights into the molecular and immunologic changes associated with cutaneous T-cell lymphomas should ultimately lead to the identification of novel therapeutic targets and the development of improved therapeutic options for patients with these malignancies.

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

    PubMed Central

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

    1995-01-01

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

  7. In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study

    PubMed Central

    Gratzinger, Dita; Harrison, Cameron; Brody, Joshua D.; Czerwinski, Debra K.; Ai, Weiyun Z.; Morales, Anjali; Abdulla, Farah; Xing, Leon; Navi, Daniel; Tibshirani, Robert J.; Advani, Ranjana H.; Lingala, Bharathi; Shah, Sumit; Hoppe, Richard T.; Levy, Ronald

    2012-01-01

    We have developed and previously reported on a therapeutic vaccination strategy for indolent B-cell lymphoma that combines local radiation to enhance tumor immunogenicity with the injection into the tumor of a TLR9 agonist. As a result, antitumor CD8+ T cells are induced, and systemic tumor regression was documented. Because the vaccination occurs in situ, there is no need to manufacture a vaccine product. We have now explored this strategy in a second disease: mycosis fungoides (MF). We treated 15 patients. Clinical responses were assessed at the distant, untreated sites as a measure of systemic antitumor activity. Five clinically meaningful responses were observed. The procedure was well tolerated and adverse effects consisted mostly of mild and transient injection site or flu-like symptoms. The immunized sites showed a significant reduction of CD25+, Foxp3+ T cells that could be either MF cells or tissue regulatory T cells and a similar reduction in S100+, CD1a+ dendritic cells. There was a trend toward greater reduction of CD25+ T cells and skin dendritic cells in clinical responders versus nonresponders. Our in situ vaccination strategy is feasible also in MF and the clinical responses that occurred in a subset of patients warrant further study with modifications to augment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993. PMID:22045986

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

    PubMed

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

    2014-02-01

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

  9. [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.

  10. miR-223 regulates cell growth and targets proto-oncogenes in mycosis fungoides/cutaneous T-cell lymphoma.

    PubMed

    McGirt, Laura Y; Adams, Clare M; Baerenwald, Devin A; Zwerner, Jeffrey P; Zic, John A; Eischen, Christine M

    2014-04-01

    The pathogenesis of the cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF), is unclear. MicroRNA (miRNA) are small noncoding RNAs that target mRNA leading to reduced mRNA translation. Recently, specific miRNA were shown to be altered in CTCL. We detected significantly reduced expression of miR-223 in early-stage MF skin, and further decreased levels of miR-223 in advanced-stage disease. CTCL peripheral blood mononuclear cells and cell lines also had reduced miR-223 as compared with controls. Elevated expression of miR-223 in these cell lines reduced cell growth and clonogenic potential, whereas inhibition of miR-223 increased cell numbers. Investigations into putative miR-223 targets with oncogenic function, including E2F1 and MEF2C, and the predicted miR-223 target, TOX, revealed that all three were targeted by miR-223 in CTCL. E2F1, MEF2C, and TOX proteins were decreased with miR-223 overexpression, whereas miR-223 inhibition led to increased protein levels in CTCL. In addition, we showed that the 3'-UTR of TOX mRNA was a genuine target of miR-223. Therefore, reduced levels of miR-223 in MF/CTCL lead to increased expression of E2F1, MEF2C, and TOX, which likely contributes to the development and/or progression of CTCL. Thus, miR-223 and its targets may be useful for the development of new therapeutics for MF/CTCL.

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

    PubMed Central

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

    2011-01-01

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

  12. A randomized cross-over study to compare PUVA and extracorporeal photopheresis in the treatment of plaque stage (T2) mycosis fungoides.

    PubMed

    Child, F J; Mitchell, T J; Whittaker, S J; Scarisbrick, J J; Seed, P T; Russell-Jones, R

    2004-05-01

    PUVA is a well-established and effective treatment for plaque stage mycosis fungoides (MF) but its use is limited on a long-term basis because of the risk of cutaneous carcinogenesis. A further disadvantage is that nonexposed areas (sanctuary sites) often develop persistent disease. Therefore it is important to find alternative methods of treatment. Extracorporeal photopheresis (ECP) is a form of photochemotherapy that involves exposure of white blood cells to UVA with psoralens and can be effective in Sézary syndrome and erythrodermic cutaneous T-cell lymphoma. The aim of this study was to compare the efficacy of PUVA and ECP in the treatment of patients with T2 plaque stage (Stage 1B) MF who had a detectable peripheral blood T-cell clone. The study was of a cross-over design. Sixteen patients were randomized to receive either PUVA twice weekly for 3 months followed by ECP once monthly for 6 months at relapse, or vice-versa. Response was assessed by monthly skin scores and peripheral blood T-cell clonality. Ten patients received PUVA initially and six ECP initially. Eight patients completed the study. Skin scores taken at the completion of each treatment arm in patients who completed the study were 113 units better (confidence interval, 42-184 units) following 3 months PUVA than 6 months ECP (P = 0.002). Peripheral blood T-cell clones were detectable in all patients post-treatment. This study indicates that ECP is not effective in the treatment of plaque stage (1B/T2) MF even in patients with molecular evidence of a peripheral blood T-cell clone. Although PUVA was more effective than ECP, neither treatment modality cleared malignant T-cells from the peripheral blood.

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

    PubMed

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

    2016-01-01

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

  14. 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

  15. 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

  16. Altered expression of Bcl-2, c-Myc, H-Ras, K-Ras, and N-Ras does not influence the course of mycosis fungoides

    PubMed Central

    Maj, Joanna; Jankowska-Konsur, Alina; Plomer-Niezgoda, Ewa; Sadakierska-Chudy, Anna

    2013-01-01

    Introduction Data about genetic alterations in mycosis fungoides (MF) are limited and their significance not fully elucidated. The aim of the study was to explore the expression of various oncogenes in MF and to assess their influence on the disease course. Material and methods Skin biopsies from 27 MF patients (14 with early MF and 13 with advanced disease) and 8 healthy volunteers were analyzed by real-time polymerase chain reaction (PCR) to detect Bcl-2, c-Myc, H-Ras, K-Ras and N-Ras expression. All PCR reactions were performed using an Applied Biosystems 7900HT Fast Real-Time PCR System and interpreted using Sequence Detection Systems software which utilizes the comparative delta Ct method. The level of mRNA was normalized to GAPDH expression. All data were analyzed statistically. Results All evaluated oncogenes were found to be expressed in the skin from healthy controls and MF patients. Bcl-2 (–4.2 ±2.2 vs. –2.2 ±1.1; p = 0.01), H-Ras (–3.0 ±3.3 vs. 0.6 ±2.6; p = 0.01) and N-Ras (–3.6 ±2.0 vs. –1.1 ±2.4; p = 0.03) were expressed at significantly lower levels in MF. No relationships between oncogene expression and disease stage, presence of distant metastases and survival were observed (p > 0.05 for all comparisons). Conclusions The pathogenic role and prognostic significance of analyzed oncogenes in MF seem to be limited and further studies are needed to establish better prognostic factors for patients suffering from MF. PMID:24273576

  17. 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

  18. 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

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

    PubMed

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

    2014-05-01

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

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

    PubMed Central

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

    2016-01-01

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

  1. 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

  2. Epidermolysis bullosa

    MedlinePlus

    ... is present at birth Dental problems such as tooth decay Hoarse cry, cough, or other breathing problems Tiny ... treating people with epidermolysis bullosa. Eat a healthy diet. When you have a lot of skin injury, ...

  3. T cells and T-cell subsets in mycosis fungoides and parapsoriasis. A study of 18 cases with anti-human T-cell monoclonal antibodies and histochemical techniques.

    PubMed

    Buechner, S A; Winkelmann, R K; Banks, P M

    1984-07-01

    Skin lesions from 15 patients with mycosis fungoides (MF) and from three with parapsoriasis were studied immunohistochemically with monoclonal antibodies against T cells (Leu 1) and against T-cell subsets (Leu 2a, Leu 3a). Lymphoid cell reactivity was diverse among these sampled cases. In two cases of parapsoriasis and nine of MF, there was a predominance of helper/inducer (Leu-3a-reactive) cells over suppressor/cytotoxic (Leu-2a-reactive) cells. In one case of parapsoriasis and one (advanced tumor stage) of MF, there was suppressor/cytotoxic cell predominance. One case of MF showed strong reactivity for both T-cell subset markers. Four cases of MF (two plaque-stage and two tumor-stage) featured a predominant cell type in the dermis which was nonreactive for all three antibodies. The intraepidermal lymphoid cellularity was Leu-1-reactive in ten cases of MF and two of parapsoriasis. Among these 12 cases, the intraepidermal cellularity was Leu-2a-reactive in four and Leu-3a-reactive in three. The use of such studies of T-cell subsets on in situ cutaneous lymphoid infiltrates may demonstrate a correlation with cytomorphology, clinical stage, and disease prognosis.

  4. Fine mapping of chromosome 10q deletions in mycosis fungoides and sezary syndrome: identification of two discrete regions of deletion at 10q23.33-24.1 and 10q24.33-25.1.

    PubMed

    Wain, E Mary; Mitchell, Tracey J; Russell-Jones, Robin; Whittaker, Sean J

    2005-02-01

    Previous cytogenetic studies in mycosis fungoides (MF) and Sezary syndrome (SS) have identified a large and poorly defined area of chromosomal deletion on chromosome 10q. We report an extensive fine-mapping allelotyping study using 19 microsatellite markers in the region 10q22.3-10q26.13. Allelic loss was identified by loss of heterozygosity analysis in 26 of 60 (43%) cases: 15 of 45 (33%) with MF and 11 of 15 (73%) with SS. MF and SS samples showed similar patterns of allelic loss with the identification of two discrete regions of deletion which were mutually exclusive in all but two cases. Within the first region of deletion at 10q23.33-10q24.1, around microsatellite marker D10S185 (2.77 Mb), 23 genes were identified, including three (KIF11, HHEX, and HELLS) with functions that, if dysregulated, could be critical in MF and SS. The second region of deletion, 10q24.33-10q25.1, around microsatellite marker D10S530 (3.92 Mb), encodes 11 genes, the majority of which have poorly identified functions. This extensive allelotyping study provides the basis for future highly selective candidate gene analyses.

  5. Persistence of human T cell lymphotropic virus type 1 (HTLV-1) sequences in peripheral blood mononuclear cells from patients with mycosis fungoides [published erratum appears in J Exp Med 1995 Jan 1;181(1):441

    PubMed Central

    1994-01-01

    Mycosis fungoides (MF) is a rare form of cutaneous T cell lymphoma suspected of having a viral etiology. As in adult T cell leukemia, the virus involved may be human T lymphotropic virus type 1 (HTLV-1). We cultured the peripheral blood mononuclear cells (PBMC) of 29 patients with MF HTLV-1 seronegative by enzyme-linked immunosorbent assay and Western blot. The presence of reverse transcriptase (RT) and p24 antigen was investigated in the concentrate supernatant of the culture. The DNA of all studied patients was submitted to polymerase chain reaction and Southern blot analysis using primers and probes recognizing the tax region of HTLV-1/2 and the pol region of HTLV-1. 10 of 29 patients were found positive to HTLV-1, whereas they were always negative to RT and p24. The same results were confirmed in double blind after 6 mo. Our findings suggest HTLV-1 may be involved in the etiology of MF, at least in certain cases. PMID:7964473

  6. 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

  7. TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC).

    PubMed

    Kim, Youn H; Willemze, Rein; Pimpinelli, Nicola; Whittaker, Sean; Olsen, Elise A; Ranki, Annamari; Dummer, Reinhard; Hoppe, Richard T

    2007-07-15

    Currently availabel staging systems for non-Hodgkin lymphomas are not useful for clinical staging classification of most primary cutaneous lymphomas. The tumor, node, metastases (TNM) system used for mycosis fungoides (MF) and Sézary syndrome (SS) is not appropriate for other primary cutaneous lymphomas. A usable, unified staging system would improve the communication about the state of disease, selection of appropriate management, standardization of enrollment/response criteria in clinical trials, and collection/analysis of prospective survival data. Toward this goal, during the recent meetings of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC), the representatives have established a consensus proposal of a TNM classification system applicable for all primary cutaneous lymphomas other than MF and SS. Due to the clinical and pathologic heterogeneity of the cutaneous lymphomas, the currently proposed TNM system is meant to be primarily an anatomic documentation of disease extent and not to be used as a prognostic guide.

  8. 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

    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

    2011-06-20

    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.

  9. 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

  10. Pretibial epidermolysis bullosa.

    PubMed

    Rizzo, Carina; Anandasabapathy, Niroshana; Walters, Ruth F; Rosenman, Karla; Kamino, Hideko; Prystowsky, Steven; Schaffer, Julie V

    2008-01-01

    A 47-year-old Vietnamese woman presented with dystrophic fingernails and toenails that had been present since infancy. She also had developed, in the third decade, pretibial pruritus with vesicle formation and progressive localized papules and scars. Multiple family members were similarly affected. Physical examination showed lichenoid papules that coalesced into large plaques that were studded with milia over the pretibial areas and 20 nail dystrophy. A biopsy specimen showed milia-like structures and dermal fibrosis. Pretibial epidermolysis bullosa is a rare variant of dystrophic epidermolysis bullosa that shows appreciable clinical overlap with dystrophic epidermolysis bullosa pruginosa. Both disease subsets are characterized by the late age of onset, nail dystrophy, and predominantly pretibial pruritic lichenoid skin lesion; they are associated with glycine substitution mutations in COL7A1. PMID:19061625

  11. 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 | ...

  12. 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

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. 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 ...

  17. 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 ...

  18. 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

  19. Epidermolysis bullosa in animals: a review.

    PubMed

    Medeiros, Gildenor X; Riet-Correa, Franklin

    2015-02-01

    Epidermolysis bullosa (EB) is a hereditary mechanobullous disease of animals and humans, characterized by an extreme fragility of the skin and mucous membranes. The main feature of EB in humans and animals is the formation of blisters and erosions in response to minor mechanical trauma. Epidermolysis bullosa is caused by mutations in the genes that code for structural proteins of the cytoskeleton of the basal keratinocytes or of the basement membrane zone. Based on the ultrastructural levels of tissue separation, EB is divided into the following three broad categories: epidermolysis bullosa simplex, junctional epidermolysis bullosa and dystrophic epidermolysis bullosa. Human types of EB are divided into several subtypes based on their ultrastructural changes and the mode of inheritance; subtypes are not fully established in animals. In humans, it is estimated that EB affects one in 17,000 live births; the frequency of EB in different animals species is not known. In all animal species, except in buffalo with epidermolysis bullosa simplex, multifocal ulcers are observed on the gums, hard and soft palates, mucosa of the lips, cheek mucosa and dorsum of the tongue. Dystrophic or absent nails, a frequent sign seen in human patients with EB, corresponds to the deformities and sloughing of the hooves in ungulates and to dystrophy or atrophy of the claws in dogs and cats. This review covers aspects of the molecular biology, diagnosis, classification, clinical signs and pathology of EB reported in animals. PMID:25354580

  20. EPIDERMOLYSIS BULLOSA IN THE NEWBORN.

    PubMed

    2016-01-01

    We present the case of a new-born baby girl who was delivered at term to a young primigravida mother. The pregnancy was booked late and had no antenatal medical or surgical complications. The baby was born vaginally and had a normal initial examination. However after three hours of birth the baby started to develop skin blisters after minor trauma/friction. The baby was seen by a Dermatologist who diagnosed the condition to be Epidermolysis Bullosa. This hereditary condition is extremely rare, and even rarer is such an early presentation in a neonate. It is caused by mutations in the genes coding for the structural proteins of the skin and is characterized by development of vesicles and blisters. The mainstay of management is supportive care. The baby was discharged on request of the parents on second day of life without any complications. PMID:27323591

  1. 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.

  2. Gastric mycosis following gastric resection and vagotomy.

    PubMed Central

    Rehnberg, O; Faxen, A; Haglund, U; Kewenter, J; Stenquist, B; Olbe, L

    1982-01-01

    In a prospective five-year follow-up study of 289 consecutive patients subjected to antrectomy and gastroduodenostomy with or without vagotomy, 130 patients underwent gastroscopy. Gastric mycosis was present almost exclusively in patients subjected to combined antrectomy and vagotomy (36%). Gastric acidity seemed to be of only minor or no importance in the development of the mycosis. The residual volume in the gastric remnant was significantly higher in patients with gastric mycosis. The impaired emptying of the gastric remnant is most likely a vagotomy effect and may be the main reason for the development of gastric mycosis. A simple but effective method was developed to evacuate gastric yeast cell aggregates. Gastric mycosis seems to give rise to only slight symptoms, mainly nausea and foul-smelling belching, whereas the reflux of duodenal contents that often occurred in combination with gastric mycosis was more likely to cause gastritis and substantial discomfort. PMID:7092348

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

    ClinicalTrials.gov

    2016-10-19

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

  4. Inherited epidermolysis bullosa - the spectrum of complications.

    PubMed

    Murat-Sušić, Slobodna; Husar, Karmela; Skerlev, Mihael; Marinović, Branka; Babić, Irena

    2011-01-01

    Epidermolysis bullosa is a group of inherited diseases that are characterized by skin and mucosal fragility and blister formation. A wide variety of extracutaneous manifestations can develop as well as various complications of the disease such as severe anemia, growth retardation, esophageal stenosis, mutilating deformities of hands and feet, glomerulonephritis leading to chronic renal failure, and many others. One of the most important and often occurring complications is the development of cutaneous squamous cell carcinomas that grow and metastasize quickly. The objective of this paper is to give dermatologists a review of major complications encountered in patients with epidermolysis bullosa. Since these complications occur so often and can be considered to be part of the clinical picture, it is mandatory to develop a multidisciplinary well-educated team involved in follow-up and treatment of these patients. PMID:22185926

  5. 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

  6. 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

  7. 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

  8. 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

  9. Dermal eosinophilic infiltrate in junctional epidermolysis bullosa.

    PubMed

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

    2015-08-01

    Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by a split in the lamina lucida usually because of mutations in LAMA3, LAMB3 and LAMC2 resulting in absence or reduction of laminin-332. Rare subtypes of JEB have mutations in COL17A1, ITGB4, ITGA6 and ITGA3 leading to reduction or dysfunction of collagen XVII, integrin α6β4 and integrin α3. The classic finding under light microscopy is a paucicellular, subepidermal split. We describe the unusual presence of an eosinophilic infiltrate in the bullae and subjacent dermis in a neonate with JEB, generalized intermediate (formerly known as non-Herlitz-type JEB), discuss the histologic differential diagnosis for a subepidermal blister in a neonate, review the literature regarding cases of epidermolysis bullosa (EB) presenting with inflammatory infiltrates, and discuss mechanisms to explain these findings. This case highlights that eosinophils can rarely be seen in EB and should not mislead the dermatopathologist into diagnosing an autoimmune blistering disorder. PMID:25950805

  10. 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

  11. 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

  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. [Acute pseudo-membranous laryngitis in epidermolysis bullosa acquisita].

    PubMed

    Lecomte, H; Folia, M; Muller, G; Gilbert, D; Tron, F; Besancenot, J-F; Romanet, P

    2010-05-01

    Epidermolysis bullosa acquisita is a rare entity belonging to the auto-immune cutaneous blistering disorders of the dermo-epidermal junction. Clinical manifestations are generally cutaneous including the development of sub-epidermal blisters. Mucosal manifestations should be systematically looking for, but laryngeal involvement remains uncommon. We report an 81-year-old woman who presented with dysphagia, dyspnea and dysphonia as the presenting features of laryngeal involvement of an epidermolysis bullosa acquisita. This is the tenth reported case in the literature. We describe our diagnostic approach and the therapeutic management, comparing them with the literature.

  14. 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

  15. Concha bullosa mucocele and mucopyocele: a series of 4 cases.

    PubMed

    Al-Sebeih, Khalid H; Bu-Abbas, Mohd H

    2014-01-01

    Concha bullosa is an aerated turbinate in the nose. It is a common anatomic variant that can develop a mucocele if obstructed, which can further progress to become a mucopyocele if infected. A mucopyocele can expand and cause destruction of neighboring tissues. A review of the literature revealed only 10 cases previously reported. We describe 2 cases of mucocele and 2 cases of mucopyocele.

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

    ERIC Educational Resources Information Center

    Jones, Sheila Dove; Miller, Cynthia Dieterich

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

  17. [Education on caring for children with inherited epidermolysis bullosa].

    PubMed

    Corset, Isabelle; Bourdon-Lanoy, Eva; Bodemer, Christine

    2013-01-01

    Inherited epidermolysis bullosa is a rare dermatological disease that requires specific daily care. An education programme teaches parents how to bathe their children in optimal conditions described in a care protocol that encourages contact and promotes the parent-child relationship.

  18. Epidermolysis bullosa nevus in a patient with recessive dystrophic epidermolysis bullosa: a case report.

    PubMed

    Fening, Katherine; Theos, Amy; Andea, Aleodor; Vincent, Bethaney; Busam, Klaus; McKay, Kristopher

    2014-12-01

    We present a case of a 6-year-old girl with recessive dystrophic epidermolysis bullosa (EB) who presented with a large pigmented lesion clinically concerning for melanoma. After histological examination and fluorescent in situ hybridization analysis, diagnosis of EB nevus was performed. EB nevi are benign melanocytic neoplasms with histological findings similar to recurrent nevi occurring in all types of EB. They often mimic melanoma clinically, dermatoscopically, and histopathologically. The ability to recognize an EB nevus is essential for appropriate management of the patient. Unnecessary surgical excision in patients with already high-risk EB should be avoided. Close monitoring of these lesions is recommended because no cases of transformation to melanoma have been described.

  19. 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

  20. Epidermolysis bullosa: dental and anesthetic management of two cases.

    PubMed

    Wright, J T

    1984-02-01

    Epidermolysis bullosa (EB) is a group of rare genetic disorders which are of dental interest because of their specific oral manifestations and management difficulties. Two cases of recessive EB which may be classified clinically as the atrophicans-gravis Herlitz type are described. Dental therapy consisted of extractions and stainless steel crown restorations, with inhalation general anesthesia. The need for and advantages of early preventive and restorative dental care are illustrated by the cases presented.

  1. 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

  2. [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

  3. [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

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

    PubMed

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

    2015-01-01

    Insects depend upon cuticular, humoral and cellular defenses to resist mycosis. However, entomopathogenic fungi through co-evolution have developed mechanisms to counter such defenses. Although a plethora of mechanisms of mycosis by entomopathogenic fungi are well-established, studies on the impairment of insects' antioxidative enzymes during mycosis remain elusive. Here, we used the interaction of Sternochetus mangiferae and its associated entomopathogenic fungus, Aspergillus flavus, as a model to validate our hypothesis. Uninfected insects were exposed to fungal spores for infection to occur. We observed symptoms of mycosis within 48 h of incubation period. Biochemical studies on antioxidative enzymes namely catalase, peroxidase and phenoloxidase, in infected and uninfected insects revealed decreased activity of these enzymes. It appears that A. flavus disables the host's antioxidative enzyme system that plays a crucial role in elimination of oxidative toxins produced during mycosis. PMID:25446036

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

    NASA Astrophysics Data System (ADS)

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

    1994-02-01

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

  6. Successful hypothermia treatment of hypoxic-ischemic encephalopathy in a neonate with epidermolysis bullosa.

    PubMed

    Karadag, Nilgun; Beken, Serdar; Dilli, Dilek; Zenciroglu, Aysegul; Okumus, Nurullah

    2014-08-01

    Despite advances in the neonatal care, hypoxic ischemic encephalopathy in late preterm and term infants remains an important cause of morbidity and mortality. There is lack of data on the application of therapeutic hypothermia in the existence of severe skin lesions. Epidermolysis bullosa is a rare group of inherited conditions which causes blisters in skin and mucosal membranes. In this report, the authors describe a successful whole-body hypothermia treatment of severe hypoxic ischemic encephalopathy in a term newborn with dystrophic epidermolysis bullosa. They observed that therapeutic hypothermia may also be given in newborns with dystrophic epidermolysis bullosa without any complications.

  7. Dystrophic epidermolysis bullosa associated with amniotic band syndrome.

    PubMed

    Snadecki, Haley; Criscione, Vincent; Jaquith, Alisha; Hay, Beverly; Deng, April; Wiss, Karen

    2014-01-01

    Amniotic band syndrome (ABS) is a term used to describe congenital anomalies that result from the entrapment of a fetus in fibrous bands. We describe two male infants born with features of dystrophic epidermolysis bullosa (DEB) and ABS. These cases add to the few previous reports of simultaneous DEB and ABS. Abnormal type VII collagen in anchoring structures of the amniotic epithelium is a proposed mechanism for loose amniotic bands that entangle the fetus, with an abnormality in the gene that encodes for type VII collagen.

  8. 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

  9. High-dose tocopherol acetate therapy in epidermolysis bullosa siblings of the Cockayne-Touraine type.

    PubMed

    Shirakata, Y; Shiraishi, S; Sayama, K; Shinmori, H; Miki, Y

    1993-11-01

    We have employed a successful therapy for epidermolysis bullosa with high-dose oral tocopherol acetate. Two siblings with dominant dystrophic epidermolysis bullosa of the Cockayne-Touraine type were reported. Both siblings suffered from tense blisters and erosions healing with scars and transient milia on the extremities. Electron microscopic study of the blisters revealed a cleavage beneath the lamina densa in both siblings. High-dose oral tocopherol acetate therapy was administered to them with satisfactory clinical reduction of the blister formation.

  10. HLA and epidermolysis bullosa: evidence for independent assortment of Weber-Cockayne subtype of epidermolysis bullosa and HLA complex.

    PubMed

    Vaidya, S; Tyring, S K; Feldkamp, M; Johnson, L B; Fine, J D

    1991-05-01

    The purpose of this study was to examine the genetic linkage (but not the association) between HLA complex and Weber-Cockayne Subtype of epidermolysis bullosa (EBS-WC). We HLA typed 44 members of three multi-generation families in which 24 members have the clinical evidence of EBS-WC. The patterns of inheritance of various HLA haplotypes and the disease were mathematically analyzed to estimate frequency of recombination (i.e. genetic distance) between HLA complex and the disease by calculating Lod Scores for each family separately as well as all for three families combined. Our results show that only one family had a positive Lod Score. The Lod Scores for the remaining two families as well as the combined Lod Score for all three families were negative. These data suggest that odds are against the genetic linkage between HLA complex and Weber-Cockayne Subtype of epidermolysis bullosa and in favor of independent assortment of the disease and HLA complex.

  11. 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

  12. 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

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

    PubMed

    Ludwig, Ralf

    2015-01-01

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

  14. 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.

  15. Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa.

    PubMed

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

    2016-01-01

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

  16. Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa

    PubMed Central

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

    2016-01-01

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

  17. 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

  18. Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa.

    PubMed

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

    2016-01-01

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

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

    PubMed

    Hoberg, E P; Abrams, A

    2005-04-01

    A relationship for Pseudostertagia bullosa within the trichostrongyloids has been enigmatic or unresolved. Studies of the synlophe in males and females of P. bullosa revealed a tapering system anterior to the deirids and a pattern of parallel ridges extending to near the caudal extremity in both lateral and median fields. Structurally, the synlophe differs considerably from that seen among the Cooperiinae and exhibits homoplasy with respect to ridge systems among some Ostertagiinae. Other structural characters due to symplesiomorphy, homoplasy or because they represent autapomorphies do not serve to reveal the putative relationships for P. bullosa with other trichostrongyloids. Although somewhat equivocal, the 2-2-1 pattern of the bursa and position of rays 2 and 3 suggest an association with the Cooperinae, as postulated by Durette-Desset and others. Pseudostertagia bullosa appears to be a species that has survived in the pronghorn, Antilocapra americana, a relictual pecoran artiodactyl that occurs in xeric regions of western North America; pronghorn are the sole remnant of the late Tertiary radiation for Antilocapridae across North America. Pseudostertagia bullosa may occur in mixed infections with a number of ostertagiines in the abomasa of mule deer (Odocoileus hemionus) and domestic sheep (Ovis aries) in regions of sympatry for pronghorn and these artiodactyl hosts. PMID:15986613

  20. [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.

  1. Gutteral Pouch Mycosis and Mycotic Encephalitis in a Horse

    PubMed Central

    McLaughlin, Bruce G.; O'Brien, John L.

    1986-01-01

    A case of mycotic encephalitis in a horse with guttural pouch mycosis is described. A liquid pellet feed binder contaminated with Aspergillus sp. and erroneously mixed in a feed concentrate was a possible source of infection. ImagesFigure 1.Figure 2. PMID:17422634

  2. [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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  5. 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

  6. [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

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

    PubMed

    Ludwig, Ralf

    2015-01-01

    Epidermolysis bullosa acquisita (EBA) is an autoimmune bullous dermatosis characterized by chronic mucocutaneous blistering caused by autoantibodies directed against type VII collagen. EBA causes a high morbidity and is difficult to treat. Model systems have significantly broadened our understanding of EBA pathogenesis, leading to the identification of numerous therapeutic targets. Of these, so far, a few have been evaluated for their therapeutic potential in preclinical models. In mice, EBA can be induced by transfer of anti-type VII collagen antibodies or by immunization with the protein. The latter model, immunization-induced EBA, is ideal to test drugs for their therapeutic efficacy. Here, mice with already established disease can be treated for prolonged periods. Albeit time consuming, results from immunization-induced EBA will pave the way for clinical application in patients. As the key pathogenic principle, that is, autoantibody-induced, leukocyte-mediated tissue injury and inflammation, is shared by other diseases, these findings may have translational applications beyond EBA. PMID:26471717

  8. 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

  9. Clinical presentation, pathogenesis, diagnosis, and treatment of epidermolysis bullosa acquisita.

    PubMed

    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.

  10. Model systems duplicating epidermolysis bullosa acquisita: a methodological review.

    PubMed

    Ludwig, Ralf J

    2012-02-01

    Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin blistering disease, in which generation of autoantibodies to type VII collagen (COL7) is the key factor for pathogenesis. Much of this current understanding of EBA pathogenesis has been obtained through the development and further application of respective model systems. In vitro model systems of EBA duplicate neutrophil activation by immune complexes of COL7 and anti-COL7 antibodies. Blister induction by anti-COL7 antibodies can be reproduced ex vivo by incubation of cryosections of human skin with anti-COL7 antibodies and neutrophils. Furthermore, EBA can be induced in mice by transfer of human or rabbit anti-COL7 IgG into adult mice, or by immunization of susceptible mouse strains with an immunodominant fragment within the non-collagenous 1 domain of COL7. However, our understanding of EBA pathogenesis is largely limited to mechanisms in autoantibody-induced tissue injury. Furthermore, these model systems of EBA have not been used to a large extent to evaluate the potential of novel treatment options. To foster a broader use of these elaborate model systems to specifically address these open issues, this review focuses on a detailed description of model systems for EBA, which should allow for a broad use of these models. This will hopefully lead to a better understanding of EBA pathogenesis, as well to a benefit in patient care.

  11. 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

  12. 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

    2015-07-20

    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.

  13. 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

  14. 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

  15. 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

  16. Evaluation of Treatments for Pruritus in Epidermolysis Bullosa.

    PubMed

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

    2015-01-01

    Pruritus is a common complication in patients with epidermolysis bullosa (EB). There is limited published data about the treatments that individuals with EB use for pruritus. The objective of the current study was to determine quantitatively which treatments individuals with EB have used for pruritus and to evaluate the perceived effectiveness of these treatments in pruritus relief. A questionnaire was developed to evaluate the treatments and therapies used for pruritus in patients of all ages and for all types of EB. Questions about bathing products, moisturizers, topical products, oral medications, dressings, and alternative therapies were included. A 5-point Likert scale (-2 = relieves itch a lot, -1 = relieves itch a little, 0 = no change, 1 = increases itch a little, 2 = increases itch a lot) was used to evaluate perceived effectiveness. Patients from seven North American EB centers were invited to participate. Greasy ointments (53.4%), lotions (45.2%), creams (40.4%), and oral hydroxyzine (39.0%) were the most frequently used treatments for pruritus. Treatments that were used frequently and perceived to be the most effective included creams (mean = -1.1), topical prescription corticosteroids (mean = -1.0), oils (mean = -0.9), oral hydroxyzine (mean = -0.9), topical diphenhydramine (mean = -0.9), and vaporizing rub (menthol, camphor, eucalyptus) (mean = -0.9). Systemic opioids (mean = 0.3), adherent bandages (mean = 0.3), and bleach baths (mean = 0.2) slightly increased pruritus. Randomized controlled trials of therapies will be necessary to develop evidence-based recommendations for control of pruritus in individuals with EB. PMID:25557557

  17. An Evaluation of Treatments for Pruritus in Epidermolysis Bullosa

    PubMed Central

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

    2016-01-01

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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. Diffuse partial woolly hair in a patient with epidermolysis bullosa simplex with mottled pigmentation.

    PubMed

    Gerkowicz, Agnieszka; Trüeb, Ralph M

    2014-04-01

    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

  3. 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

  4. Use of a keratin-based hydrogel in the management of recessive dystrophic epidermolysis bullosa.

    PubMed

    Than, Martin P; Smith, Robert Allen; Cassidy, Sharon; Kelly, Robert; Marsh, Clive; Maderal, Andrea; Kirsner, Robert S

    2013-08-01

    A new keratin-based hydrogel wound dressing was applied to the neck of a patient who was suffering from recessive dystrophic epidermolysis bullosa. A significant improvement was observed in the robustness of skin in this area: reduced propensity to blister and improved healing of blisters. The improvement allowed the cessation of use of secondary dressings for this area. The factors gave a significant improvement in quality of life for the patient. PMID:22208480

  5. 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

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

    ClinicalTrials.gov

    2016-10-06

    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

  7. 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

  8. 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

  9. Long-term follow-up in 51 patients with mycosis fungoides and Sézary syndrome treated by interferon-alfa.

    PubMed

    Jumbou, O; N'Guyen, J M; Tessier, M H; Legoux, B; Dréno, B

    1999-03-01

    Although interferon-alfa (IFN-alpha) has proved effective in treating epidermotropic cutaneous T-cell lymphoma (ECTL), few studies have considered the follow-up of treated patients and whether complete remission was maintained. We studied 51 patients (one stage Ia, seven stage Ib, one stage IIa, 30 stage IIb, 11 stage III (Sézary syndrome) and one stage IV) who received low-dose IFN-alpha as monotherapy for ECTL (mean daily dose of IFN-alpha 2.7 x 106 units for 14.9 months), giving special consideration to the significance of My7 (CD13) antigen expression by epidermal basal cells in predicting the maintenance of complete remission. For a mean follow-up period of 43.4 months, the results showed 21 complete remissions, 13 partial remissions and 17 patients with stable or progressive disease. Twelve patients died during the follow-up (3-52 months). IFN-alpha led to an improved response in the early stages, with a greater number of complete remissions (P = 0.03) and partial remissions (P = 0.01). The mean time to complete remission was 4 months, regardless of clinical stage (P = 0.1). Of 21 patients in complete remission, 57% had a relapse within a mean period of 7.5 months. For patients maintained in complete remission, the mean period of response was 31 months. The length of complete remission was independent of clinical stage, and My7 antigen expression was not predictive of complete remission.

  10. Romidepsin for the treatment of relapsed/refractory cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome): Use in a community setting.

    PubMed

    Reddy, Sunil A

    2016-10-01

    Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of rare non-Hodgkin lymphomas that arise in the skin. In advanced stages, CTCL becomes systemic and is associated with poor prognosis. Diagnosis of CTCL and treatment of early-stage disease with topical therapies often occurs under the care of a dermatologist. Community oncologists see few patients with CTCL due to direct referrals from dermatologists to academic or lymphoma specialty centers. However, some patients will continue to be managed in a community setting. Currently there is no evidence-based stepwise algorithm for treatment of patients with CTCL, and guidelines suggest a wide range of systemic therapies, including biologics, targeted agents, and more traditional chemotherapies. To provide optimal care in a community setting, oncologists must become familiar with newer nonchemotherapeutic treatment options. This review highlights romidepsin, a histone deacetylase inhibitor approved for the treatment of patients with CTCL who have received ≥1 prior systemic therapy. PMID:27637355

  11. Romidepsin for the treatment of relapsed/refractory cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome): Use in a community setting.

    PubMed

    Reddy, Sunil A

    2016-10-01

    Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of rare non-Hodgkin lymphomas that arise in the skin. In advanced stages, CTCL becomes systemic and is associated with poor prognosis. Diagnosis of CTCL and treatment of early-stage disease with topical therapies often occurs under the care of a dermatologist. Community oncologists see few patients with CTCL due to direct referrals from dermatologists to academic or lymphoma specialty centers. However, some patients will continue to be managed in a community setting. Currently there is no evidence-based stepwise algorithm for treatment of patients with CTCL, and guidelines suggest a wide range of systemic therapies, including biologics, targeted agents, and more traditional chemotherapies. To provide optimal care in a community setting, oncologists must become familiar with newer nonchemotherapeutic treatment options. This review highlights romidepsin, a histone deacetylase inhibitor approved for the treatment of patients with CTCL who have received ≥1 prior systemic therapy.

  12. Transcriptome sequencing in Sézary syndrome identifies Sézary cell and mycosis fungoides-associated lncRNAs and novel transcripts

    PubMed Central

    Lee, Carolyn S.; Ungewickell, Alexander; Bhaduri, Aparna; Qu, Kun; Webster, Dan E.; Armstrong, Randall; Weng, Wen-Kai; Aros, Cody J.; Mah, Angela; Chen, Richard O.; Lin, Meihong; Sundram, Uma; Chang, Howard Y.; Kretz, Markus; Kim, Youn H.

    2012-01-01

    Sézary syndrome (SS) is an aggressive cutaneous T-cell lymphoma (CTCL) of unknown etiology in which malignant cells circulate in the peripheral blood. To identify viral elements, gene fusions, and gene expression patterns associated with this lymphoma, flow cytometry was used to obtain matched pure populations of malignant Sézary cells (SCs) versus nonmalignant CD4+ T cells from 3 patients for whole transcriptome, paired-end sequencing with an average depth of 112 million reads per sample. Pathway analysis of differentially expressed genes identified mis-regulation of PI3K/Akt, TGFβ, and NF-κB pathways as well as T-cell receptor signaling. Bioinformatic analysis did not detect either nonhuman transcripts to support a viral etiology of SS or recurrently expressed gene fusions, but it did identify 21 SC-associated annotated long noncoding RNAs (lncRNAs). Transcriptome assembly by multiple algorithms identified 13 differentially expressed unannotated transcripts termed Sézary cell-associated transcripts (SeCATs) that include 12 predicted lncRNAs and a novel transcript with coding potential. High-throughput sequencing targeting the 3′ end of polyadenylated transcripts in archived tumors from 24 additional patients with tumor-stage CTCL confirmed the differential expression of SC-associated lncRNAs and SeCATs in CTCL. Our findings characterize the SS transcriptome and support recent reports that implicate lncRNA dysregulation in human malignancies. PMID:22936659

  13. 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

  14. 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.

  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. Recessive dystrophic epidermolysis bullosa--oral rehabilitation using stereolithography and immediate endosseous implants.

    PubMed

    Oliveira, Marcio A; Ortega, Karem L; Martins, Fabiana M; Maluf, Paulo S Z; Magalhães, Marina G

    2010-01-01

    Dental management of patients with epi-dermolysis bullosa (EB) is challenging because of the severe soft tissue lesions associated with this disease. A case history is presented where two immediate endosseous implants were placed in the mandible of a patient with recessive dystrophic EB using computer-aided technology to plan the surgery and prosthetic rehabilitation. After a 24-month follow-up, the prosthesis was stable with healthy asymptomatic soft tissue around the implants. The stereolithographic model provides a precise and noninvasive copy of the mandibular and maxillary arches of patients with EB for rehabilitation of the dentition with immediate endosseous implants and a prosthesis.

  17. 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

  18. 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

  19. A Mouse Model of Generalized non-Herlitz Junctional Epidermolysis Bullosa

    PubMed Central

    Bubier, Jason A.; Sproule, Thomas J.; Petell, Lydia; Webb, Cameron; Fine, Jo-David; Roopenian, Derry C.; Sundberg, John P.

    2010-01-01

    Epidermolysis bullosa (EB) is a class of intractable, rare, genetic disorders characterized by fragile skin and blister formation as a result of dermal-epidermal mechanical instability. EB presents with considerable clinical and molecular heterogeneity. Viable animal models of junctional epidermolysis bullosa (JEB), that both mimic the human disease and survive beyond the neonatal period, are needed. We identified a spontaneous, autosomal recessive mutation (Lamc2 jeb) due to a Murine Leukemia Virus long terminal repeat insertion in Lamc2 that results in a hypomorphic allele with reduced levels of LAMC2 protein. These mutant mice develop a progressive blistering disease validated at the gross and microscopic levels to closely resemble generalized non-Herlitz JEB. The Lamc2 jeb mice display additional extracutaneous features such as loss of bone mineralization and abnormal teeth, as well as a respiratory phenotype that is recognized but not as well characterized in humans. This model faithfully recapitulates human JEB and provides an important preclinical tool to test novel therapeutic approaches. PMID:20336083

  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.

  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. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Polymeric Nanoparticles to Combat Squamous Cell Carcinomas in Patients with Dystrophic Epidermolysis Bullosa

    PubMed Central

    Rajadas, Jayakumar; Inayathullah, Mohammed

    2014-01-01

    Skin cancer is the leading cause of malignancy in the United States, with Basal Cell Carcinoma, Squamous Cell Carcinoma , and Melanoma being the three most common diagnoses, respectively. Squamous Cell Carcinoma (SCC) is a particular concern for patients suffering from Dystrophic Epidermolysis Bullosa (DEB), a disease that affects the production and function of collagen VII, a protein that forms the anchoring fibrils which bind the epidermis to the dermis. Patients with DEB suffer from chronic blistering and wounds that have impaired healing capabilities, often leading to the development of SCC and eventual mortality. Nanomedicine is playing an increasing role in the delivery of effective therapeutics to combat a wide range of diseases, including the imaging and treatment of SCC. In this review, we discuss the role of nanoparticles in the treatment of SCC with an emphasis on PLGA nanoparticles and SCCs found in patients suffering from DEB, and address recent patents that are pertinent to the development of novel nanomedical therapeutics. PMID:25506404

  8. 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

  9. 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

  10. 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

  11. Emerging pathogen in immunocompromised hosts: Exophiala dermatitidis mycosis in graft-versus-host disease.

    PubMed

    Chalkias, S; Alonso, C D; Levine, J D; Wong, M T

    2014-08-01

    Infection with the dematiaceous environmental fungus Exophiala, an emerging pathogen in immunocompromised individuals, poses a diagnostic and therapeutic challenge. Herein, we report the first Exophiala dermatitidis fungemia case, to our knowledge, in an allogeneic hematopoietic stem cell transplant patient with graft-versus-host disease, expanding the clinical setting where Exophiala species mycosis should be suspected. PMID:24890324

  12. 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 ...

  13. Understanding the outcomes of a home nursing programme for patients with epidermolysis bullosa: an Australian perspective.

    PubMed

    Stevens, Louise J; McKenna, Sue; Marty, Jennifer; Cowin, Allison J; Kopecki, Zlatko

    2016-10-01

    Epidermolysis bullosa (EB) consists of a spectrum of genodermatoses characterised by skin fragility and various degrees of skin and mucous membrane blistering. Minimal trauma and friction can cause extensive blistering in patients with EB, resulting in a number of complications. However, wound management is the main challenge for these patients because of a high risk of infection, fluid loss and potential development of aggressive squamous cell carcinoma (SCC). Indeed, patients with EB have an increased risk for developing skin cancers compared to the general population. In 2012, a home nursing programme was established in Australia to provide assistance to families or patients with severe forms of EB. Nursing care was provided to patients with severe EB during dressing changes in their homes over a period of 2 years. Both families of patients and nurses were surveyed periodically using a developed questionnaire to assess the benefits of this home nursing and its impact on the patients, their families and the nurses. Key findings included a perceived improvement in quality of life, a better provision of support and improved family life management. These findings are the first to highlight the benefits of this national home nursing programme for EB patients within Australia and demonstrate the continued need and benefit of home nursing for patients with severe skin blistering disorders.

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Apocytolysis, a proposed mechanism of blister formation in epidermolysis bullosa simplex.

    PubMed

    El-Hawary, Marwa S; Abdel-Halim, Mona R E; Sayed, Safinaz S; Abdelkader, Heba A

    2015-05-01

    Epidermolysis bullosa simplex (EBS) is caused by keratin 5 and 14 mutations. In vitro studies revealed that susceptibility to caspase 8-mediated apoptosis is increased in keratin 14 mutated keratinocytes. We aimed to investigate the role of apoptotic/inflammatory pathways in the pathogenesis of EBS by studying the expression of caspase 8 in lesional and non-lesional skin compared to controls. Ten EBS patients proved by electron microscopy and five age and sex matched healthy volunteers were the subjects of this case control study. Caspase 8 expression was studied by immunohistochemistry. Caspase 8 expression in lesional and non-lesional skin was significantly higher than in controls (p < 0.01 and p = 0.013, respectively) with no significant difference between lesional and non-lesional skin. Lesional skin had significantly higher density of dermal infiltrate (p = 0.02). Caspase 8 expression in lesional skin was significantly correlated with the extent of the disease, rate of blistering, and density of dermal infiltrate (r = 0.835; p = 0.003, r = 0.889; p = 0.001 and r = 0.776; p = 0.008 respectively). Caspase 8-mediated apoptosis is an integral component of an orchestra of events conducted by keratin mutation. Apo-cytolysis is proposed to better describe the mechanism of blistering in EBS. The small number of cases is a limitation.

  1. 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

  2. Epidermolysis bullosa simplex: a keratin 5 mutation is a fully dominant allele in epidermal cytoskeleton function.

    PubMed Central

    Stephens, K; Zlotogorski, A; Smith, L; Ehrlich, P; Wijsman, E; Livingston, R J; Sybert, V P

    1995-01-01

    To explore the relationship between abnormal keratin molecules, 10-nm intermediate filament (IF) organization, and epidermal fragility and blistering, we sought to determine the functional consequences of homozygosity for a dominant keratin defect. We describe a family with an autosomal dominant skin-blistering disorder, epidermolysis bullosa simplex, Koebner subtype (EBS-K), that has a novel point mutation, occurring in the keratin 5 gene (KRT5), that predicts the substitution of an evolutionarily conserved lysine by an asparagine residue (K173N). Unlike previous heterozygous mutations located within the initial segment of domain 1A of keratin molecules, K173N heterozygosity did not result in severe disease or clumping of keratin filaments. One family member was found to be homozygous for the K173N allele, having inherited it from each of her affected first-cousin parents. Despite a lack of normal keratin 5 molecules, and an effective doubling of abnormal molecules, available for heterodimerization with keratin 14 during IF formation, there were no significant differences in the clinical severity or the ultrastructural organization of the keratin IF cytoskeleton of the homozygous individual. These data demonstrate that the K173N mutation behaves as a fully dominant allele and indicate that a limited number of abnormal keratin molecules are sufficient to impair cytoskeletal function and elicit epidermal fragility and blistering. Images Figure 3 Figure 2 Figure 4 PMID:7534039

  3. 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

  4. Transcriptome and ultrastructural changes in dystrophic Epidermolysis bullosa resemble skin aging.

    PubMed

    Breitenbach, Jenny S; Rinnerthaler, Mark; Trost, Andrea; Weber, Manuela; Klausegger, Alfred; Gruber, Christina; Bruckner, Daniela; Reitsamer, Herbert A; Bauer, Johann W; Breitenbach, Michael

    2015-06-01

    The aging process of skin has been investigated recently with respect to mitochondrial function and oxidative stress. We have here observed striking phenotypic and clinical similarity between skin aging and recessive dystrophic Epidermolysis bullosa (RDEB), which is caused by recessive mutations in the gene coding for collagen VII,COL7A1. Ultrastructural changes, defects in wound healing, and inflammation markers are in part shared with aged skin. We have here compared the skin transcriptomes of young adults suffering from RDEB with that of sex- and age-matched healthy probands. In parallel we have compared the skin transcriptome of healthy young adults with that of elderly healthy donors. Quite surprisingly, there was a large overlap of the two gene lists that concerned a limited number of functional protein families. Most prominent among the proteins found are a number of proteins of the cornified envelope or proteins mechanistically involved in cornification and other skin proteins. Further, the overlap list contains a large number of genes with a known role in inflammation. We are documenting some of the most prominent ultrastructural and protein changes by immunofluorescence analysis of skin sections from patients, old individuals, and healthy controls.

  5. Angina bullosa hemorrhagica of the soft palate: a clinical study of 16 cases.

    PubMed

    Horie, Norio; Kawano, Ryutaro; Inaba, Junichi; Numa, Takehiro; Kato, Takao; Nasu, Daisuke; Kaneko, Takahiro; Kudo, Itsuro; Shimoyama, Tetsuo

    2008-03-01

    Angina bullosa hemorrhagica (ABH) is an oral mucosal blood blister that develops without blood dyscrasia or vesiculobullous disorder. Although a minor mucosal trauma has been suggested as a triggering factor for ABH, its etiopathogenesis, especially the causative role of systemic conditions, is largely unknown. We investigated the presence or absence of local factors as well as systemic background disease in 16 patients with ABH arising in the soft palate. All the lesions were solitary, and 75% of them (n = 12) appeared during the ingestion of hard or crispy food. With regard to underlying systemic conditions, hypertension was the most common (n = 6), and asthma, insomnia, diabetes mellitus, rheumatoid arthritis, gastrointestinal disorder and hyperuricemia were also recorded (n = 1 each). Five patients had no significant background disease. There were no recalcitrant or recurrent cases. In conclusion, the present study has revealed that scratching of the oral mucosa during eating plays an important role in the formation of ABH. Hypertension appears to be the most frequent background condition, but its pathogenic relationship with ABH remains speculative, as hypertension is fairly common in adults. PMID:18403881

  6. Reprogramming of keratin biosynthesis by sulforaphane restores skin integrity in epidermolysis bullosa simplex

    PubMed Central

    Kerns, Michelle L.; DePianto, Daryle; Dinkova-Kostova, Albena T.; Talalay, Paul; Coulombe, Pierre A.

    2007-01-01

    Epidermolysis bullosa simplex (EBS) is a rare inherited condition in which the epidermis loses its integrity after mechanical trauma. EBS is typified by the dysfunction of intermediate filaments in basal keratinocytes of epidermis. Most cases of EBS are due to mutations in the keratin 5 or 14 gene (K5 and K14), whose products copolymerize to form intermediate filaments in basal keratinocytes. Available treatments for this disorder are only palliative. Here we exploit functional redundancy within the keratin gene family as the basis for therapy. We show that genetic activation of Gli2 or treatment with a pharmacological activator of Nrf2, two transcription factors eliciting distinct transcriptional programs, alleviates the blistering caused by a K14 deficiency in an EBS mouse model, correlating with K17 induction in basal epidermal keratinocytes. Nrf2 induction is brought about by treatment with sulforaphane, a natural product. Sulforaphane thus represents an attractive option for the prevention of skin blistering associated with K14 mutations in EBS. PMID:17724334

  7. Evaluation of wound care options in patients with recessive dystrophic epidermolysis bullosa: a costly necessity.

    PubMed

    Kirkorian, Anna Yasmine; Weitz, Nicole A; Tlougan, Brook; Morel, Kimberly D

    2014-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder in which mutations in collagen VII, the main component of the anchoring fibril, lead to skin fragility and to the development of acute and chronic wounds. Wound care and dressing changes are an important part of the daily lives of individuals with RDEB. Ideal wound care should improve wound healing, minimize pain, and improve quality of life. The objective of the current study was to review wound care options that might be used in a patient with RDEB and calculate the cost of these various options based on publicly available pricing of wound care products. There is a wide range of costs for wound care options in patients with RDEB. For example, a 1-day supply of dressing for a neonate boy with RDEB ranges from $10.64 for the least expensive option to $127.54 for the most expensive option. Wound care in patients with severe, generalized RDEB has not only a significant economic effect, but also directly affects quality of life in this patient population. Although randomized controlled trials evaluating different wound care products in patients with RDEB are lacking, small studies and expert opinion support the use of specialized nonadherent dressings that minimize skin trauma and promote wound healing. Until there is a cure, prospective studies are needed to assess pain, quality of life, and wound healing associated with the use of specialized wound care products for this life-altering condition.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Cutaneous squamous cell carcinoma developing from recessive dystrophic epidermolysis bullosa: a case report and an immunohistochemical study.

    PubMed

    Tsukada, Akira; Fujimura, Taku; Furudate, Sadanori; Kambayashi, Yumi; Numata, Yukikazu; Haga, Takahiro; Hashimoto, Akira; Aiba, Setsuya

    2012-09-01

    We describe a 49-year-old Japanese woman with cutaneous squamous cell carcinoma (SCC) developing from recessive dystrophic epidermolysis bullosa (RDEB). Interestingly, immunohistochemical staining revealed dense infiltration of CD163(+) M2 macrophages and numerous Foxp3(+) regulatory T cells (Tregs) around the tumor. Since the contribution of immunosuppressive factors (e.g. TGFβ) to the carcinogenesis of SCC from RDEB was recently reported, our present findings suggest one of the possible contributions of immunosuppressive cells, such as CD163(+) M2 macrophages and Tregs, to the carcinogenesis of SCC from RDEB. PMID:23271994

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. Radiosensitive Hematopoietic Cells Determine the Extent of Skin Inflammation in Experimental Epidermolysis Bullosa Acquisita.

    PubMed

    Iwata, Hiroaki; Witte, Mareike; Samavedam, Unni Krishna S R L; Gupta, Yask; Shimizu, Atsushi; Ishiko, Akira; Schröder, Tobias; Seeger, Karsten; Dahlke, Markus; Rades, Dirk; Zillikens, Detlef; Ludwig, Ralf J

    2015-09-01

    Animal models have enhanced our understanding of the pathogenesis of autoimmune diseases. For these models, genetically identical, inbred mice have commonly been used. Different inbred mouse strains, however, show a high variability in disease manifestation. Identifying the factors that influence this disease variability could provide unrecognized insights into pathogenesis. We established a novel Ab transfer-induced model of epidermolysis bullosa acquisita (EBA), an autoimmune disease characterized by (muco)-cutaneous blistering caused by anti-type VII collagen (COL7) autoantibodies. Blistering after anti-COL7 IgG (directed against the von Willebrand factor A-like domain 2) transfer showed clear variability among inbred mouse strains, that is, severe cutaneous blistering and inflammation in C57BL/6J and absence of skin lesions in MRL/MpJ mice. The transfer of anti-COL7 IgG into irradiated, EBA-resistant MRL/MpJ mice, rescued by transplantation with bone marrow from EBA-susceptible B6.AK-H2k mice, induced blistering. To the contrary, irradiated EBA-susceptible B6.AK-H2k mice that were rescued using MRL/MpJ bone marrow were devoid of blistering. In vitro, immune complex activation of neutrophils from C57BL/6J or MRL/MpJ mice showed an impaired reactive oxygen species release from the latter, whereas no differences were observed after PMA activation. This finding was paralleled by divergent expression profiles of immune complex-activated neutrophils from either C57BL/6J or MRL/MpJ mice. Collectively, we demonstrate that radiosensitive cells determine the varying extent of skin inflammation and blistering in the end-stage effector phase of EBA. PMID:26202985

  19. 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

  20. [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

  1. 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

  2. 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

  3. [Lungs "Hassalloid´s-like" bodies in children with epidermolysis bullosa junctionalis and bart´s syndrome].

    PubMed

    Adamicová, Katarína; Balhárek, Tomáš; Fetisovová, Želmíra; Mellová, Yvetta

    2016-01-01

    Epidermolysis bullosa and Bart´s syndrome are fairly accurately documented diseases by histopathology. In the article the authors describe interesting and hitherto undescribed phenomenon in the lungs male infant with epidermolysis bullosa junctionalis and Barts syndrome, who died 17 days after birth and 13 days after surgery for pyloric atresia, on multiorgan failure within basic congenital diseases.Histologically in lung alveoli was found to the massive presence of foamy macrophages and numerous globoid formations resembling morphological and immunohistochemical "Hassall´s" bodies in a thymus of the newborn. It was a acidophillic spherical bodies concentric tracks in the connective tissue with focal presence of fibrin, as a unique proof CKAE1/AE3 and CKHMW positive epithelial cells and CD68-positive histiocytic elements. An interesting finding was the follicular skin structure in the center "hassalloid´s-like" body, which suggests an aspiration components of the skin during intrauterine life.Normal Apgar score at birth of the child (10/10/10 s.) and severe histological features on the death of the child testify for the first pathogenetic formation "hassalloid´s-like" bodies in the lungs during the 17-day life of a disabled child. PMID:27526019

  4. A novel deletion and two recurrent substitutions on type VII collagen gene in seven Iranian patients with epidermolysis bullosa

    PubMed Central

    Hamidi, Armita Kakavand; Moghaddam, Mohammad; Hatamnejadian, Nasim; Ebrahimi, Ahmad

    2016-01-01

    Objective(s): Epidermolysis bullosa is one of the most important series of mechano-bullous heritable skin disorders which is categorized into four major types according to the layer that bullae forms within basement membrane zone. In dystrophic form of the disease, blisters are made in the sublamina densa zone, at the level of type VII collagen protein which produce anchoring fibrils. Type VII collagen gene is the only responsible gene for this form. The aim of this study was to survey causative mutations of type VII collagen gene among Iranian patients with epidermolysis bullosa. Materials and Methods: For this purpose, exons 73-75 were investigated by polymerase chain reaction followed by direct sequencing. Results: In current study, we found three different point mutations in type VII collagen alleles in 7 out of 50 patients. Four patients were homozygous for a new deletion which resulted in frame shift (p.Pro2089fs). Two patients were homozygous for a recurrent glycine substitution (p.G2031S) and one patient was detected with an allele carrying a substitution (p.R2069C). Conclusion: The results emphasized heterogeneity in the type VII collagen gene and will provide a sign for early diagnosis and future study of the disease pathogenesis. PMID:27746867

  5. T cells are required for the production of blister-inducing autoantibodies in experimental epidermolysis bullosa acquisita.

    PubMed

    Sitaru, Ana Gabriela; Sesarman, Alina; Mihai, Sidonia; Chiriac, Mircea T; Zillikens, Detlef; Hultman, Per; Solbach, Werner; Sitaru, Cassian

    2010-02-01

    Epidermolysis bullosa acquisita is a prototypical organ-specific autoimmune disease caused by autoantibodies against type VII collagen of the dermal-epidermal junction. Although mechanisms of autoantibody-induced blister formation were extensively characterized, the initiation of autoantibody production in autoimmune blistering diseases is still poorly defined. In the current study, we addressed the role of T cells for the production of blister-inducing autoantibodies in mice immunized with type VII collagen. To detect autoreactive type VII collagen-specific T cells, lymph node cells from immunized SJL mice were stimulated in vitro with recombinant Ag, and their proliferation was measured by radioactive thymidine incorporation and flow cytometry analysis of CFSE-labeled cells. Interestingly, using synthetic peptides of the immunogen, partly different T and B cell epitopes in mice immunized with type VII collagen were demonstrated. In contrast to wild-type mice, immunization with type VII collagen of SJL athymic nude mice lacking T cells did not induce an autoimmune response and blistering phenotype. Importantly, SJL nude mice repleted with T cells from immunized wild-type mice showed a robust and durable autoantibody production resulting in subepidermal blistering disease in the recipients. Our present results demonstrate that T cells are required for the initiation of autoimmunity against type VII collagen in experimental epidermolysis bullosa acquisita and provide a basis for developing T cell-directed immunomodulatory strategies for this and related autoimmune diseases.

  6. Gene Editing for the Efficient Correction of a Recurrent COL7A1 Mutation in Recessive Dystrophic Epidermolysis Bullosa Keratinocytes

    PubMed Central

    Chamorro, Cristina; Mencía, Angeles; Almarza, David; Duarte, Blanca; Büning, Hildegard; Sallach, Jessica; Hausser, Ingrid; Del Río, Marcela; Larcher, Fernando; Murillas, Rodolfo

    2016-01-01

    Clonal gene therapy protocols based on the precise manipulation of epidermal stem cells require highly efficient gene-editing molecular tools. We have combined adeno-associated virus (AAV)-mediated delivery of donor template DNA with transcription activator-like nucleases (TALE) expressed by adenoviral vectors to address the correction of the c.6527insC mutation in the COL7A1 gene, causing recessive dystrophic epidermolysis bullosa in a high percentage of Spanish patients. After transduction with these viral vectors, high frequencies of homology-directed repair were found in clones of keratinocytes derived from a recessive dystrophic epidermolysis bullosa (RDEB) patient homozygous for the c.6527insC mutation. Gene-edited clones recovered the expression of the COL7A1 transcript and collagen VII protein at physiological levels. In addition, treatment of patient keratinocytes with TALE nucleases in the absence of a donor template DNA resulted in nonhomologous end joining (NHEJ)-mediated indel generation in the vicinity of the c.6527insC mutation site in a large proportion of keratinocyte clones. A subset of these indels restored the reading frame of COL7A1 and resulted in abundant, supraphysiological expression levels of mutant or truncated collagen VII protein. Keratinocyte clones corrected both by homology-directed repair (HDR) or NHEJ were used to regenerate skin displaying collagen VII in the dermo-epidermal junction. PMID:27045209

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  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. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

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

    SciTech Connect

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

    1995-01-01

    Laminin 5 consists of three polypeptides, {alpha}3, {beta}3, and {gamma}2, encoded by the genes LAMA3, LAMB3, and LAMC2, respectively. In this study, we have elucidated the exon-intron organization of the human LAMB3 gene. Characterization of five overlapping {lambda} phage DNA clones revealed that the gene was approximately 29 kb in size. Subsequent sequence data revealed that the gene consisted of 23 exons that varied from 64 to 379 bp in size, accounting for the full-length cDNA with an open reading frame of 3516 hp encoding 1172 amino acids. Comparison of the LAMB3 gene structure with the previously characterized LAMB1 gene revealed that LAMB3 was considerably more compact. Knowledge of the exon-intron organization of the LAMB3 gene will facilitate elucidation of mutations in patients with the junctional forms of epidermolysis bullosa, some of which have been associated with mutations in the laminin 5 genes. 33 refs., 3 figs., 2 tabs.

  20. Progress 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. [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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. Complete Cytolysis and Neonatal Lethality in Keratin 5 Knockout Mice Reveal Its Fundamental Role in Skin Integrity and in Epidermolysis Bullosa Simplex

    PubMed Central

    Peters, Bettina; Kirfel, Jutta; Büssow, Heinrich; Vidal, Miguel; Magin, Thomas M.

    2001-01-01

    In human patients, a wide range of mutations in keratin (K) 5 or K14 lead to the blistering skin disorder epidermolysis bullosa simplex. Given that K14 deficiency does not lead to the ablation of a basal cell cytoskeleton because of a compensatory role of K15, we have investigated the requirement for the keratin cytoskeleton in basal cells by inactivating the K5 gene in mice. We report that the K5−/− mice die shortly after birth, lack keratin filaments in the basal epidermis, and are more severely affected than K14−/− mice. In contrast to the K14−/− mice, we detected a strong induction of the wound-healing keratin K6 in the suprabasal epidermis of cytolyzed areas of postnatal K5−/− mice. In addition, K5 and K14 mice differed with respect to tongue lesions. Moreover, we show that in the absence of K5 and other type II keratins, residual K14 and K15 aggregated along hemidesmosomes, demonstrating that individual keratins without a partner are stable in vivo. Our data indicate that K5 may be the natural partner of K15 and K17. We suggest that K5 null mutations may be lethal in human epidermolysis bullosa simplex patients. PMID:11408584

  14. Aphanomyces invadans and ulcerative mycosis in estuarine and freshwater fish in Florida.

    PubMed

    Sosa, Emilio R; Landsberg, Jan H; Stephenson, Christy M; Forstchen, Ann B; Vandersea, Mark W; Litaker, R Wayne

    2007-03-01

    In the spring of 1998, the Florida Fish and Wildlife Research Institute received numerous reports of lesioned or ulcerated fish primarily from the St. Lucie Estuary on the southeast coast of Florida, an area known since the late 1970s for lesions of the ulcerative mycosis (UM) type. From these and archived reports, as well as others received from different areas of Florida, we documented that diseased specimens had randomly distributed skin ulcers (usually reddened or hemorrhagic) with raised irregular margins and, in some cases, deeply penetrating hyphae in the surrounding muscle tissue. Since 1998, 256 fish (comprising 18 species) with ulcerative lesions (from 15 different locations) were confirmed with hyphae in fresh squash preparation or by histological evaluation. Squash preparations revealed nonseptate, sparsely branching, thick-walled hyphae; histological sections revealed mycotic granulomas in the dermis that occasionally penetrated into the skeletal muscle. These pathological characteristics were consistent with UM caused by the oomycete Aphanomyces invadans in Southeast Asia, Japan, Australia, and the United States. For specific identification, six isolates from ulcerated fish were cultured and prepared for molecular characterization using established diagnostic methods. Ribosomal RNA gene sequence analysis identified three isolates as Aphanomyces invadans, one as the oomycete Achlya bisexualis, and two as the ascomycete Phialemonium dimorphosporum. A more extensive survey of 67 ulcerated skin samples from fish collected between 1998 and 2003 was performed using a polymerase chain reaction assay specific for Aphanomyces invadans. Of these, 26 (38.8%) samples from seven fish species and nine collection locations were positive. Confirmation of UM associated with Aphanomyces invadans represents new host records in Florida for the sheepshead Archosargus probatocephalus, striped mullet Mugil cephalus, white mullet Mugil curema, silver perch Bairdiella

  15. Recommendations for the management of candidemia in neonates in Latin America. Latin America Invasive Mycosis Network.

    PubMed

    Santolaya, María E; Alvarado Matute, Tito; de Queiroz Telles, Flavio; Colombo, Arnaldo Lopes; Zurita, Jeannete; Tiraboschi, Iris Nora; Cortes, Jorge Alberto; Thompson-Moya, Luis; Guzman-Blanco, Manuel; Sifuentes, Jose; Echevarría, Juan; Nucci, Marcio

    2013-01-01

    Candidemia is one of the most frequent opportunistic mycoses worldwide. Limited epidemiological studies in Latin America indicate that incidence rates are higher in this region than in the Northern Hemisphere. Diagnosis is often made late in the infection, affecting the initiation of antifungal therapy. A more scientific approach, based on specific parameters, for diagnosis and management of candidemia in Latin America is warranted. 'Recommendations for the diagnosis and management of candidemia' are a series of manuscripts that have been developed by members of the Latin America Invasive Mycosis Network. They aim to provide a set of best-evidence recommendations for the diagnosis and management of candidemia. This publication, 'Recommendations for the management of candidemia in neonates in Latin America', was written to provide guidance to healthcare professionals on the management of neonates who have, or who are at risk of, candidemia. Computerized searches of existing literature were performed by PubMed. The data were extensively reviewed and analyzed by members of the group. The group also met on two occasions to pose questions, discuss conflicting views, and deliberate on a series of management recommendations. 'Recommendations for the management of candidemia in neonates in Latin America' includes prophylaxis, empirical therapy, therapy for proven candidemia, patient work-up following diagnosis of candidemia, central venous catheter management, and management of complications. This manuscript is the fourth of this series that deals with diagnosis and treatment of invasive candidiasis. Other publications in this series include: 'Recommendations for the diagnosis of candidemia in Latin America', 'Recommendations for the management of candidemia in adults in Latin America', and 'Recommendations for the management of candidemia in children in Latin America'. PMID:23756219

  16. Recommendations for the management of candidemia in children in Latin America. Latin America Invasive Mycosis Network.

    PubMed

    Santolaya, María E; de Queiroz Telles, Flavio; Alvarado Matute, Tito; Colombo, Arnaldo Lopes; Zurita, Jeannete; Tiraboschi, Iris Nora; Cortes, Jorge Alberto; Thompson-Moya, Luis; Guzman-Blanco, Manuel; Sifuentes, Jose; Echevarría, Juan; Nucci, Marcio

    2013-01-01

    Candidemia is one of the most frequent opportunistic mycoses worldwide. Limited epidemiological studies in Latin America indicate that incidence rates are higher in this region than in the Northern Hemisphere. Diagnosis is often made late in the infection, affecting the initiation of antifungal therapy. A more scientific approach, based on specific parameters, for diagnosis and management of candidemia in Latin America is warranted. 'Recommendations for the diagnosis and management of candidemia' are a series of manuscripts that have been developed by members of the Latin America Invasive Mycosis Network. They aim to provide a set of best-evidence recommendations for the diagnosis and management of candidemia. This publication, 'Recommendations for the management of candidemia in children in Latin America', was written to provide guidance to healthcare professionals on the management of children who have, or who are at risk of, candidemia. Computerized searches of existing literature were performed by PubMed. The data were extensively reviewed and analyzed by members of the group. The group also met on two occasions to pose questions, discuss conflicting views, and deliberate on a series of management recommendations. 'Recommendations for the management of candidemia in children in Latin America' includes prophylaxis, empirical therapy, therapy for proven candidemia, patient work-up following diagnosis of candidemia, duration of candidemia treatment, and central venous catheter management in children with candidemia. This manuscript is the third of this series that deals with diagnosis and treatment of invasive candidiasis. Other publications in this series include: 'Recommendations for the diagnosis of candidemia in Latin America', 'Recommendations for the management of candidemia in adults in Latin America', and 'Recommendations for the management of candidemia in neonates in Latin America'. PMID:23764557

  17. 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

  18. 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

  19. 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

  20. 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

  1. One Novel Frameshift Mutation on Exon 64 of COL7A1 Gene in an Iranian Individual Suffering Recessive Dystrophic Epidermolysis Bullosa.

    PubMed

    Khaniani, Mahmoud Shekari; Sohrabi, Nasrin; Derakhshan, Neda Mansoori; Derakhshan, Sima Mansoori

    2015-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is an extremely rare subtype of bullous dermatosis caused by the COL7A1 gene mutation. After genomic DNA extraction from the peripheral blood sample of all subjects (3 pedigree members and 3 unrelated control individuals), COL7A1 gene screening was performed by PCR amplification and direct DNA sequencing of all of the coding exons and flanking intronic regions. Genetic analysis of the COL7A1 gene in an affected individual revealed a novel mutation: c.5493delG (p.K1831Nfs*10) in exon 64 of the COL7A1 gene in homozygous state. This mutation was not discovered in 3 unrelated Iranian control individuals. These data suggest that c.5493delG may influence the phenotype of RDEB. The result of this case report contributes to the expanding database on COL7A1 mutations.

  2. 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

  3. 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

  4. 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.

  5. Two novel mutations on exon 8 and intron 65 of COL7A1 gene in two Chinese brothers result in recessive dystrophic epidermolysis bullosa.

    PubMed

    Lin, Ying; Chen, Xue-Jun; Liu, Wei; Gong, Bo; Xie, Jun; Xiong, Jun-Hao; Cheng, Jing; Duan, Xi-Ling; Lin, Zhao-Chun; Huang, Lu-Lin; Wan, Hui-Ying; Liu, Xiao-Qi; Song, Lin-Hong; Yang, Zheng-Lin

    2012-01-01

    Dystrophic epidermolysis bullosa is an inherited bullous dermatosis caused by the COL7A1 gene mutation in autosomal dominant or recessive mode. COL7A1 gene encodes type VII collagen - the main component of the anchoring fibrils at the dermal-epidermal junction. Besides the 730 mutations reported, we identified two novel COL7A1 gene mutations in a Chinese family, which caused recessive dystrophic epidermolysis bullosa (RDEB). The diagnosis was established histopathologically and ultrastructurally. After genomic DNA extraction from the peripheral blood sample of all subjects (5 pedigree members and 136 unrelated control individuals), COL7A1 gene screening was performed by polymerase chain reaction amplification and direct DNA sequencing of the whole coding exons and flanking intronic regions. Genetic analysis of the COL7A1 gene in affected individuals revealed compound heterozygotes with identical novel mutations. The maternal mutation is a 2-bp deletion at exon 8 (c.1006_1007delCA), leading to a subsequent reading frame-shift and producing a premature termination codon located 48 amino acids downstream in exon 9 (p.Q336EfsX48), consequently resulting in the truncation of 2561 amino acids downstream. This was only present in two affected brothers, but not in the other unaffected family members. The paternal mutation is a 1-bp deletion occurring at the first base of intron 65 (c.IVS5568+1delG) that deductively changes the strongly conserved GT dinucleotide at the 5' donor splice site, results in subsequent reading-through into intron 65, and creates a stop codon immediately following the amino acids encoded by exon 65 (GTAA→TAA). This is predicted to produce a truncated protein lacking of 1089 C-terminal amino acids downstream. The latter mutation was found in all family members except one of the two unaffected sisters. Both mutations were observed concurrently only in the two affected brothers. Neither mutation was discovered in 136 unrelated Chinese control

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Effect of Septal Deviation, Concha Bullosa and Haller’s Cell on Maxillary Sinus’s Inferior Pneumatization; a Retrospective Study

    PubMed Central

    Göçmen, Gökhan; Borahan, Mehmet Oğuz; Aktop, Sertac; Dumlu, Asım; Pekiner, Filiz Namdar; Göker, Kamil

    2015-01-01

    Purpose: Maxillary sinus’s inferior pneumatization is a physiological process, which increase with time and accelerates following extraction. The aim of this study was to determine the prevalence of nasal septal deviation (NSD), concha bullosa (CB), and Haller’s cells (HC) and to examine the correlation of maxillary sinus inferior pneumatization (MSIP) with these anatomical variations. Material and Methods : 300 (150 m, 150 f) CBCT scans taken at the Marmara University School of Dentistry from 2011 to 2014 were retrospectively reviewed for the presence of CB, NSD, HC and MSIP. The correlation between pneumatization to the anatomic variants was then compared. Data were analyzed with a Chi-square test. Results : Of the 300 CBCT scans, 44.3% have CB, 37.3% NSD, 19.3% HC and 27.7% MSIP. There was no statistical significancewhen comparing the relationship of patients with CB, NSD, HC and pneumatization. Conclusion : NSD, CB and HC do not have a definite role on sinus’s inferior pneumatization. Further studies should be conducted including potential factors related pneumatization with more sample size for further correlation with NSD, CB,HC. PMID:26464596

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy.

    PubMed

    Bornert, Olivier; Kühl, Tobias; Bremer, Jeroen; van den Akker, Peter C; Pasmooij, Anna Mg; Nyström, Alexander

    2016-08-01

    Genetically evoked deficiency of collagen VII causes dystrophic epidermolysis bullosa (DEB)-a debilitating disease characterized by chronic skin fragility and progressive fibrosis. Removal of exons carrying frame-disrupting mutations can reinstate protein expression in genetic diseases. The therapeutic potential of this approach is critically dependent on gene, protein, and disease intrinsic factors. Naturally occurring exon skipping in COL7A1, translating collagen VII, suggests that skipping of exons containing disease-causing mutations may be feasible for the treatment of DEB. However, despite a primarily in-frame arrangement of exons in the COL7A1 gene, no general conclusion of the aptitude of exon skipping for DEB can be drawn, since regulation of collagen VII functionality is complex involving folding, intra- and intermolecular interactions. To directly address this, we deleted two conceptually important exons located at both ends of COL7A1, exon 13, containing recurrent mutations, and exon 105, predicted to impact folding. The resulting recombinantly expressed proteins showed conserved functionality in biochemical and in vitro assays. Injected into DEB mice, the proteins promoted skin stability. By demonstrating functionality of internally deleted collagen VII variants, our study provides support of targeted exon deletion or skipping as a potential therapy to treat a large number of individuals with DEB. PMID:27157667

  18. 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

  19. Premature termination codons on both alleles of the type VII collagen gene (COL7A1) in three brothers with recessive dystrophic epidermolysis bullosa.

    PubMed Central

    Christiano, A M; Suga, Y; Greenspan, D S; Ogawa, H; Uitto, J

    1995-01-01

    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. In the most severe, dystrophic (scarring) forms of EB, blisters form below the cutaneous basement membrane at the level of the anchoring fibrils, which are composed of type VII collagen. Ultrastructural observations of altered anchoring fibrils and genetic linkage to the type VII collagen locus (COL7A1) have implicated COL7A1 as the candidate gene in the dystrophic forms of EB. We have recently cloned the entire cDNA and the gene for human COL7A1. In this study, we describe distinct mutations in both COL7A1 alleles in three brothers with severe, mutilating recessive dystrophic EB (the Hallopeau-Siemens type, HS-RDEB). The patients are compound heterozygotes for two different mutations, both of which result in a premature termination codon in COL7A1, and the parents were shown to be clinically heterozygous carries of the respective mutations. Premature termination codons in both alleles of COL7A1 appear to be the underlying cause of severe, recessive dystrophic EB in this family. Images PMID:7883979

  20. Mechlorethamine

    MedlinePlus

    ... of cancer that begin in a type of white blood cells that normally fights infection); mycosis fungoides (a type ... rashes); certain types of leukemia (cancer of the white blood cells), including chronic lymphocytic leukemia (CLL) and chronic myelogenous ...

  1. Fludarabine Injection

    MedlinePlus

    ... leukemia (CLL; a type of cancer of the white blood cells) in adults who have already been treated with ... NHL; cancer that begins in a type of white blood cell that normally fights infection) and mycosis fungoides (a ...

  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. 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 ...

  4. Pagetoid Reticulosis: Report of Two Cases and Review of the Literature

    PubMed Central

    Larson, Krista; Wick, Mark R.

    2016-01-01

    Pagetoid reticulosis is a rare variant of mycosis fungoides that presents with a large, usually single, erythematous, slowly growing scaly plaque containing an intraepidermal proliferation of neoplastic T lymphocytes. Histopathologically, this disease has distinctive attributes. In this report, we present two cases of pagetoid reticulosis, compare its microscopic features to those of ‘classical’ mycosis fungoides, and provide a brief review of the pertinent literature. PMID:27195265

  5. 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

  6. 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

  7. Monozygotic twins discordant for recessive dystrophic epidermolysis bullosa phenotype highlight the role of TGF-β signalling in modifying disease severity.

    PubMed

    Odorisio, Teresa; Di Salvio, Michela; Orecchia, Angela; Di Zenzo, Giovanni; Piccinni, Eugenia; Cianfarani, Francesca; Travaglione, Antonella; Uva, Paolo; Bellei, Barbara; Conti, Andrea; Zambruno, Giovanna; Castiglia, Daniele

    2014-08-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is a genodermatosis characterized by fragile skin forming blisters that heal invariably with scars. It is due to mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils connecting the cutaneous basement membrane to the dermis. Identical COL7A1 mutations often result in inter- and intra-familial disease variability, suggesting that additional modifiers contribute to RDEB course. Here, we studied a monozygotic twin pair with RDEB presenting markedly different phenotypic manifestations, while expressing similar amounts of collagen VII. Genome-wide expression analysis in twins' fibroblasts showed differential expression of genes associated with TGF-β pathway inhibition. In particular, decorin, a skin matrix component with anti-fibrotic properties, was found to be more expressed in the less affected twin. Accordingly, fibroblasts from the more affected sibling manifested a profibrotic and contractile phenotype characterized by enhanced α-smooth muscle actin and plasminogen activator inhibitor 1 expression, collagen I release and collagen lattice contraction. These cells also produced increased amounts of proinflammatory cytokines interleukin 6 and monocyte chemoattractant protein-1. Both TGF-β canonical (Smads) and non-canonical (MAPKs) pathways were basally more activated in the fibroblasts of the more affected twin. The profibrotic behaviour of these fibroblasts was suppressed by decorin delivery to cells. Our data show that the amount of type VII collagen is not the only determinant of RDEB clinical severity, and indicate an involvement of TGF-β pathways in modulating disease variability. Moreover, our findings identify decorin as a possible anti-fibrotic/inflammatory agent for RDEB therapeutic intervention. PMID:24599399

  8. Overexpression of the Flii gene increases dermal-epidermal blistering in an autoimmune ColVII mouse model of epidermolysis bullosa acquisita.

    PubMed

    Kopecki, Zlatko; Arkell, Ruth M; Strudwick, Xanthe L; Hirose, Misa; Ludwig, Ralf J; Kern, Johannes S; Bruckner-Tuderman, Leena; Zillikens, Detlef; Murrell, Dedee F; Cowin, Allison J

    2011-11-01

    Epidermolysis bullosa (EB) is a severe genetic skin fragility syndrome characterized by blister formation. The molecular basis of EB is still largely unknown and wound healing in patients suffering from EB remains a major challenge to their survival. Our previous studies have identified the actin remodelling protein Flightless I (Flii) as an important mediator of wound repair. Here we identify Flii as a novel target involved in skin blistering. Flii expression was significantly elevated in 30 patients with EB, most prominently in patients with recessive dystrophic EB (RDEB) who have defects in production of type VII collagen (ColVII). Using an autoimmune ColVII murine model of EB acquisita (EBA) and an immunocompetent-ColVII-hypomorphic genetic mouse model of RDEB together with murine Flii alleles, we investigated the contribution of Flii to EB. Overexpression of Flii produced severe blistering post-induction of EBA, while decreased Flii reduced blister severity, elevated integrin expression, and improved ColVII production. Flii(+/-) blistered skin showed reduced α-SMA, TGF-β1, and Smad 2/3 expression, suggesting that decreasing Flii may affect fibrosis. In support of this, Flii-deficient fibroblasts from EBA mice were less able to contract collagen gels in vitro; however, addition of TGF-β1 restored collagen contraction, suggesting an interplay between Flii and TGF-β1. Elevated Flii gene and protein expression was further observed in the blisters of ColVII hypomorphic mice, a murine model of RDEB, suggesting that reducing Flii in blistered skin could be a potential new approach for treating patients with EB.

  9. Prenatal diagnosis for recessive dystrophic epidermolysis bullosa in 10 families by mutation and haplotype analysis in the type VII collagen gene (COL7A1).

    PubMed Central

    Christiano, A. M.; LaForgia, S.; Paller, A. S.; McGuire, J.; Shimizu, H.; Uitto, J.

    1996-01-01

    BACKGROUND: Epidermolysis bullosa (EB) is a group of heritable diseases that manifest as blistering and erosions of the skin and mucous membranes. In the dystrophic forms of EB (DEB), the diagnostic hallmark is abnormalities in the anchoring fibrils, attachment structures beneath the cutaneous basement membrane zone. The major component of anchoring fibrils is type VII collagen, and DEB has been linked to the type VII collagen gene (COL7A1) at 3p21, with no evidence for locus heterogeneity. Due to life-threatening complications and significant long-term morbidity associated with the severe, mutilating form of recessive dystrophic EB (RDEB), there has been a demand for prenatal diagnosis from families with affected offspring. MATERIALS AND METHODS: Intragenic polymorphisms in COL7A1 and flanking microsatellite markers on chromosome 3p21, as well as detection of pathogenetic mutations in families, were used to perform PCR-based prenatal diagnosis from DNA obtained by chorionic villus sampling at 10-15 weeks or amniocentesis at 12-15 weeks gestation in 10 families at risk for recurrence of RDEB. RESULTS: In nine cases, the fetus was predicted to be normal or a clinically unaffected carrier of a mutation in one allele. These predictions have been validated in nine cases by the birth of a healthy child. In one case, an affected fetus was predicted, and the diagnosis was confirmed by fetal skin biopsy. CONCLUSIONS: DNA-based prenatal diagnosis of RDEB offers an early, expedient method of testing which will largely replace the previously available invasive fetal skin biopsy at 18-20 weeks gestation. Images FIG. 1 FIG. 3 PMID:8900535

  10. 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

  11. 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

  12. 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.

  13. Mycosis Inhibits Grasshopper Necrophagy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Necrophagy is common among the Acrididae and the tettigonid, Anabrus simplex; 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 not eat cadavers tha...

  14. 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

  15. 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.

  16. 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.

  17. Dysphagia caused by focal guttural pouch mycosis: mononeuropathy of the pharyngeal ramus of the vagal nerve in a 20-year-old pony mare

    PubMed Central

    2013-01-01

    A 20-year-old pony mare was presented to the equine hospital with a ten-day history of dysphagia, regurgitation and coughing. An obstruction of the oesophagus was excluded via endoscopy, but the proximal oesophagus appeared to be distended and circular contractions were missing. A guttural pouch endoscopy revealed a single, black-mottled plaque on the pharyngeal ramus of the vagus nerve in the left guttural pouch, causing a local swelling of this nerve. The pharyngeal ramus seemed to be atrophic distal to the lesion. A biopsy was taken from the lesion and histopathological findings proved the reasonable suspicion of a guttural pouch mycosis with a high degree of purulent-necrotic inflammation and invasion of fungal hyphae. There were no signs of neoplasia, such as melanoma. Daily guttural pouch irrigations with a clotrimazole emulsion (20 g Canesten® Gyn4 solved in 500 ml water), led to a good recovery of the mucosa above the nerve. Periodic endoscopic examination of the left guttural pouch showed that local thickening and distal atrophy of this pharyngeal ramus did not improve, neither did the clinical symptoms. Due to progressive weight loss, acute respiratory distress and aspiration pneumonia, the 20-year-old pony mare unfortunately had to be euthanized three weeks after discharge. This case report emphasizes the enormous importance of a single nerve for the realization of the swallowing process. The one-sided loss of function of the pharyngeal branch of the vagal nerve cannot be compensated neither by the remaining ipsilateral nerves nor by the contralateral normal functioning glossopharyngeal and vagal nerves and thus inevitably leads to severe dysphagia. PMID:23845027

  18. Biological insights into the pathogenesis of cutaneous T-cell lymphomas (CTCL).

    PubMed

    Whittaker, Sean

    2006-02-01

    Mycosis fungoides and Sezary syndrome, collectively known as cutaneous T-cell lymphomas (CTCLs), are low-grade, indolent, clonal, non-Hodgkin's lymphomas consisting of CD4+ CD45RO+ T cells with a CLA+ CCR4+ skin-homing phenotype. There are several variants of primary CTCLs with differences in clinical behavior and prognosis. Currently, the precise etiologies of mycosis fungoides and Sezary syndrome are unknown. This article reviews our current understanding of the pathogenetic abnormalities involving genomic mutations, abnormal cDNA expression, and dysregulation of signaling pathways in CTCL.

  19. Follicular Mucinosis in a Male Adolescent with a History of Acute Myelogenous Leukemia and Graft-versus-Host Disease.

    PubMed

    Jefferson, Julie; Taube, Janis; Grossberg, Anna

    2016-01-01

    Although many cases of follicular mucinosis are idiopathic, numerous others are associated with mycosis fungoides or, rarely, other neoplastic or inflammatory disorders. There are only three reported cases, all in adults, of follicular mucinosis arising in association with acute myelogenous leukemia, two of which involved mycosis fungoides-associated follicular mucinosis, including one case in which the patient had a preceding bone marrow transplant. We present the first reported case of follicular mucinosis arising in an adolescent with acute myelogenous leukemia and acute graft-versus-host disease after an allogeneic bone marrow transplantation. PMID:26645410

  20. 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.

    PubMed Central

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

    1996-01-01

    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-->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 healing 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. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8644730

  1. Loss of heterozygosity on 10q and microsatellite instability in advanced stages of primary cutaneous T-cell lymphoma and possible association with homozygous deletion of PTEN.

    PubMed

    Scarisbrick, J J; Woolford, A J; Russell-Jones, R; Whittaker, S J

    2000-05-01

    Previous cytogenetic studies of primary cutaneous T-cell lymphoma (CTCL) were based on limited numbers of patients and seldom showed consistent nonrandom chromosomal abnormalities. In this study, 54 tumor DNA samples from patients with CTCL were analyzed for loss of heterozygosity on 10q. Allelic loss was identified in 10 samples, all of which were from the 44 patients with mycosis fungoides (10/44 patients; 23%). Of the patients with allelic loss, 3 were among the 29 patients with early-stage myosis fungoides (T(1) or T(2)) (3/29 patients; 10%), whereas the other 7 were among the 15 patients with advanced cutaneous disease (T(3) or T(4)) (7/15 patients; 47%). The overlapping region of deletion was between 10q23 and 10q24. In addition, microsatellite instability (MSI) was present in 13 of the 54 samples (24%), 12 from patients with mycosis fungoides and 1 from a patient with Sezary syndrome. There was also an association between MSI and disease progression in patients with mycosis fungoides, with 6 of 15 (40%) patients with MSI having advanced cutaneous disease and only 6 of 29 (21%) having early-stage disease. Samples with allelic loss on 10q were analyzed for abnormalities of the tumor suppressor gene PTEN (10q23.3). No tumor-specific mutations were detected, but homozygous deletion was found in 2 patients. Thus, we found loss of heterozygosity on 10q and MSI in advanced cutaneous stages of mycosis fungoides. These findings indicate that a tumor suppressor gene or genes in this region may be associated with disease progression. Furthermore, abnormalities of PTEN may be important in the pathogenesis of mycosis fungoides, but our data imply that this gene is rarely inactivated by small deletions or point mutations. (Blood. 2000;95:2937-2942)

  2. Granulomatous Lymphoproliferative Disorders: Granulomatous Slack Skin and Lymphomatoid Granulomatosis.

    PubMed

    Gangar, Pamela; Venkatarajan, Sangeetha

    2015-07-01

    Granulomatous cutaneous T-cell lymphomas (CTCL) and lymphomatoid granulomatosis are considered granulomatous lymphoproliferative disorders. The most common types of granulomatous CTCL are granulomatous mycosis fungoides and granulomatous slack skin. Lymphomatoid granulomatosis is a rare Epstein-Barr virus driven lymphoproliferative disorder. This article reviews the etiopathogenesis, clinical presentation, systemic associations, and management of both granulomatous slack skin syndrome and lymphomatoid granulomatosis. PMID:26143428

  3. 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 ...

  4. 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 ...

  5. The use of Monte Carlo technique to optimize the dose distribution in total skin irradiation

    NASA Astrophysics Data System (ADS)

    Poli, M. E. R.; Pereira, S. A.; Yoriyaz, H.

    2001-06-01

    Cutaneous T-cell lymphoma (mycosis fungoides) is an indolent disease with a low percentage of cure. Total skin irradiation using an electron beam has become an efficient treatment of mycosis fungoides with curative intention, with success in almost 40% of the patients. In this work, we propose the use of a Monte Carlo technique to simulate the dose distribution in the patients during total skin irradiation treatments. Use was made of MCNP-4B, a well known and established code used to simulate transport of electrons, photons and neutrons through matter, especially in the area of reactor physics, and also finding increasing utility in medical physics. The goal of our work is to simulate different angles between each beam with a fixed treatment distance in order to obtain a uniform dose distribution in the patient.

  6. Treatment of childhood cutaneous T-cell lymphoma with alpha-interferon plus PUVA.

    PubMed

    Tay, Y K; Weston, W L; Aeling, J L

    1996-01-01

    All forms of cutaneous T-cell lymphoma are rare in childhood. We describe an 8-year-old boy with plaque-stage mycosis fungoides stage IIA whose cutaneous eruption had been present for 5 years. Histologic examination revealed the presence of a granulomatous infiltrate together with atypical lymphocytes within the dermis. The child had an excellent response to combination psoralen-UVA (PUVA) with interferon-alpha 2a treatment and is currently in remission.

  7. An unusual case of granulomatous slack skin disease with necrobiosis.

    PubMed

    Benton, Emma Clare; Morris, Stephen L; Robson, Alistair; Whittaker, Sean J

    2008-10-01

    Granulomatous slack skin disease (GSS) is a very rare form of T-cell lymphoma, with only 52 cases reported in the literature. In the recent World Health Organization-European Organization for Research and Treatment of Cancer consensus classification GSS is considered to be a variant of mycosis fungoides. We describe a patient with GSS and histologic evidence of necrobiosis, which has not been previously reported.

  8. 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.

  9. Novel therapeutic agents for cutaneous T-Cell lymphoma

    PubMed Central

    2012-01-01

    Mycosis fungoides (MF) and Sezary Syndrome (SS) represent the most common subtypes of primary Cutaneous T-cell lymphoma (CTCL). Patients with advanced MF and SS have a poor prognosis leading to an interest in the development of new therapies with targeted mechanisms of action and acceptable safety profiles. In this review we focus on such novel strategies that have changed the treatment paradigm of this rare malignancy. PMID:22594538

  10. 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

  11. 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.

  12. 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

  13. Alopecias due to drugs and other skin and systemic disorders.

    PubMed

    Guzmán-Sánchez, Daniela; Asz-Sigall, Daniel

    2015-01-01

    In this chapter, we will discuss the most common alopecias due to drugs and other skin and systemic disorders. The following hair disorders will be analyzed: telogen effluvium (acute and chronic); anagen effluvium; folliculotropic mycosis fungoides; and folliculitis due to bacteria, fungi, parasites, human immunodeficiency virus disease, lupus erythematosus, and sarcoidosis. We will cover topics including the epidemiology, etiology, clinical picture, and diagnosis of and current treatments for each disease. PMID:26370648

  14. 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

  15. 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.

  16. Endemic mycosis complicating human immunodeficiency virus infection.

    PubMed Central

    Sarosi, G A; DAvies, S F

    1996-01-01

    Persons infected with the human immunodeficiency virus are prone to the development of many fungal diseases. Normal hosts with intact immunity usually recover from infection by these less-invasive fungi. In persons with compromised T-cell-mediated immunity, however, widespread dissemination from a pulmonary focus occurs. In this review, we discuss the epidemiology, clinical manifestations, diagnosis, and treatment of the three major North American mycoses, histoplasmosis, blastomycosis, and coccidioidomycosis. In most cases, amphotericin B is the initial drug of choice, followed by one of the azoles for lifelong maintenance therapy. PMID:8732733

  17. Spectrum of p53 gene mutations suggests a possible role for ultraviolet radiation in the pathogenesis of advanced cutaneous lymphomas.

    PubMed

    McGregor, J M; Crook, T; Fraser-Andrews, E A; Rozycka, M; Crossland, S; Brooks, L; Whittaker, S J

    1999-03-01

    There is evidence that the incidence of primary cutaneous lymphoma, like other forms of non-Hodgkin's lymphoma, is increasing, yet little is known of the pathogenetic events involved in this group of disorders. In this study we examine the frequency and spectrum of P53 gene mutations in a large series of primary cutaneous lymphomas, with particular emphasis on tumor stage mycosis fungoides, as it is in these cases that p53 overexpression has previously been reported. Sixty-six samples from 55 patients with primary cutaneous B cell and T cell lymphomas were analyzed for mutations in exons 5-9 of the P53 gene using polymerase chain reaction/single strand conformational polymorphism, and subsequent cloning and sequencing of genomic DNA. Fourteen separate P53 mutations were identified in blood, skin, and lymph node samples in 13 patients (24%). Twelve of 14 mutations occurred at dipyrimidine sites, eight resulting in C-->T transitions and one in a CC-->TT tandem base transition, a mutation spectrum strikingly similar to that reported in nonmelanoma skin cancer and characteristic of DNA damage caused by ultraviolet B radiation. In the subset of patients with mycosis fungoides, P53 mutations were identified in six of 17 patients with tumor-stage but in none of 12 patients with plaque-stage disease (Fisher's exact test p = 0.027). These data suggest a role for ultraviolet radiation in the pathogenesis of primary cutaneous lymphomas and a possible ultraviolet B-related step in the progression of mycosis fungoides from plaque to tumor-stage disease.

  18. 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

  19. 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

  20. 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

  1. Widespread atypical vascular lesions of the skin after whole-body electron beam therapy: expanding the clinical spectrum.

    PubMed

    Sinclair, Werner

    2013-02-01

    Atypical vascular lesion of the skin is an uncommon usually benign condition, thus far reported almost exclusively from mammary skin after radiotherapy for carcinoma of the breast. Some clinical and histological overlap exists with early angiosarcoma, which can also occur on irradiated skin. The lesions are divided into vascular and lymphatic types, the first representing a higher risk for development of angiosarcoma and the latter being more common. This article reports a rare case of widespread, progressive, vascular-type atypical vascular lesion after repeated whole-body electron beam irradiation administered as treatment for mycosis fungoides.

  2. 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

  3. Management of cutaneous T cell lymphoma: new and emerging targets and treatment options

    PubMed Central

    Li, Janet Y; Horwitz, Steven; Moskowitz, Alison; Myskowski, Patricia L; Pulitzer, Melissa; Querfeld, Christiane

    2012-01-01

    Cutaneous T cell lymphomas (CTCL) clinically and biologically represent a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the most common subtypes. Over the last decade, new immunological and molecular pathways have been identified that not only influence CTCL phenotype and growth, but also provide targets for therapies and prognostication. This review will focus on recent advances in the development of therapeutic agents, including bortezomib, the histone deacetylase inhibitors (vorinostat and romidepsin), and pralatrexate in CTCL. PMID:22457602

  4. Clinical and pathological heterogeneity in cutaneous gamma-delta T-cell lymphoma: a report of three cases and a review of the literature.

    PubMed

    Munn, S E; McGregor, J M; Jones, A; Amlot, P; Rustin, M H; Russell Jones, R; Whittaker, S

    1996-12-01

    Cutaneous gamma-delta (gamma delta) T-cell lymphoma is rare. Eleven cases have been reported to date including four cases of mycosis fungoides (MF), two of pagetoid reticulosis and five of pleomorphic cutaneous T-cell lymphoma (CTCL). We report three further cases of cutaneous gamma delta T-cell lymphoma; one of MF, one of a pleomorphic CTCL and one of a subcutaneous T-cell lymphoma. Combined data suggest that although cutaneous gamma delta T-cell lymphomas do not appear to comprise a single clinicopathological entity, they may be associated with aggressive clinical behaviour and a poor prognosis.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Case for diagnosis.

    PubMed

    Pedrosa, Ana Filipa; Ferreira, Olga; Barros, Ana Margarida; Nogueira, Ana; Bettencourt, Herberto; Azevedo, Filomena

    2013-01-01

    Ketron-Goodman disease was formerly considered a disseminated type of pagetoid reticulosis. However, according to the new classification consensus, it should be regarded as aggressive epidermotropic CD8 T-cutaneous lymphoma, cutaneous gamma/delta T-lymphoma, or tumor-stage mycosis fungoides, depending on the clinical-histological picture. This case highlights a rare and challenging presentation of Ketron-Goodman disease with an indolent presentation and evolution and good response to a low-grade treatment regimen, not fitting well into the new classification criteria. PMID:24173195

  11. Romidepsin for cutaneous T-cell lymphoma.

    PubMed

    Prince, H Miles; Dickinson, Michael; Khot, Amit

    2013-12-01

    Cutaneous T-cell lymphomas are relatively rare lymphomas and the most common form is mycosis fungoides. Its rare leukemic variant is Sezary syndrome. Advanced-stage disease is typically treated with bexarotene (a retinoid), IFN-α or conventional chemotherapeutic agents, but relapses are inevitable. Histone deacetylase inhibitors that modify the epigenome are an attractive addition to the armamentarium. Based on two large Phase II studies, the US FDA approved intravenous romidepsin for patients with relapsed/refractory cutaneous T-cell lymphomas. Romidepsin provides a subset of patients with an opportunity for prolonged clinical responses with a tolerable side-effect profile.

  12. 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

  13. [Familial form of tropical spastic paraparesis. Report of 4 families].

    PubMed

    Cartier, L; Ramírez, E; Galeno, H

    1998-04-01

    We report eight patients with familial tropical spastic paraparesis belonging to four families. The diagnosis was reached by clinical, radiological and electrophysiological studies. Human lymphotropic virus type I infection was confirmed by ELISA, immunofluorescence essays. Western blot and polymerase chain reaction in DNA of peripheral blood mononuclear cells, using primers for tax and 5'ltr genes. In all these families there was a vertical transmission of the disease from the first to the second generation. All patients improved their spastic gait after prednisone treatment. Among patients of the second generation, all had dacrysialoadenitis, three had leukemia like lymphocytes in the blood smear, two had mycosis fungoides and one had hepatic cirrhosis.

  14. 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

  15. 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

  16. Radiation Therapy for Cutaneous T-Cell Lymphomas.

    PubMed

    Tandberg, Daniel J; Craciunescu, Oana; Kelsey, Chris R

    2015-10-01

    Radiation therapy is an extraordinarily effective skin-directed therapy for cutaneous T-cell lymphomas. Lymphocytes are extremely sensitive to radiation and a complete response is generally achieved even with low doses. Radiation therapy has several important roles in the management of mycosis fungoides. For the rare patient with unilesional disease, radiation therapy alone is potentially curative. For patients with more advanced cutaneous disease, radiation therapy to local lesions or to the entire skin can effectively palliate symptomatic disease and provide local disease control. Compared with other skin-directed therapies, radiation therapy is particularly advantageous because it can effectively penetrate and treat thicker plaques and tumors. PMID:26433843

  17. Granulomatous slack skin T-cell lymphoma: an important differential diagnosis with giant cell tumor of soft tissue.

    PubMed

    Adriano, André Ricardo; Lima, Tiago Silveira; Battistella, Maxime; Bagot, Martine

    2015-01-01

    Granulomatous slack skin is an indolent T-cell lymphoma, considered to be a variant of mycosis fungoides. Clinically it is characterized by areas of redundant skin, wrinkled, inelastic, with variable erythema and infiltration besides a poikilodermic surface. A differential diagnosis unknown to most dermatologists is the giant cell tumor of soft tissue, which is an extremely rare low-grade sarcoma. The authors report a patient who had undergone extensive surgery because of a primary diagnosis of giant cell tumor of soft tissue, but which proved to be granulomatous slack skin after a second interventional procedure with confirmatory histopathology. PMID:26734874

  18. Granulomatous slack skin T-cell lymphoma: an important differential diagnosis with giant cell tumor of soft tissue*

    PubMed Central

    Adriano, André Ricardo; Lima, Tiago Silveira; Battistella, Maxime; Bagot, Martine

    2015-01-01

    Granulomatous slack skin is an indolent T-cell lymphoma, considered to be a variant of mycosis fungoides. Clinically it is characterized by areas of redundant skin, wrinkled, inelastic, with variable erythema and infiltration besides a poikilodermic surface. A differential diagnosis unknown to most dermatologists is the giant cell tumor of soft tissue, which is an extremely rare low-grade sarcoma. The authors report a patient who had undergone extensive surgery because of a primary diagnosis of giant cell tumor of soft tissue, but which proved to be granulomatous slack skin after a second interventional procedure with confirmatory histopathology. PMID:26734874

  19. 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

  20. PLCG1 Gene Mutations in Cutaneous T-Cell Lymphomas Revisited.

    PubMed

    Tensen, Cornelis P

    2015-09-01

    The observation that mutations in the phospholipase C gamma 1 (PLCG1) gene (among which p.S345F was shown to be activating) are frequent (20%) in tumoral cutaneous T-cell lymphoma (CTCL) samples raised the possibility of targeting therapies against the PLCG1 signaling pathway. However, new data by Caumont et al. in this issue of JID show that PLCG1 mutations are far less prevalent than expected in CTCLs, which tempers the initial enthusiasm. This new study finds that only 3-5% of the CTCL tumor genomes (mycosis fungoides and Sézary syndrome) harbor PLCG1 mutations. PMID:26269406

  1. Methotrexate and Pralatrexate.

    PubMed

    Wood, Gary S; Wu, Jianqiang

    2015-10-01

    This article reviews methotrexate and the more potent, related compound, pralatrexate, for the treatment of cutaneous T-cell lymphomas, including mycosis fungoides, Sézary syndrome, and CD30+ lymphoproliferative disorders. Although these folate antagonists are traditionally viewed as antiproliferative cell cycle inhibitors, it is recognized that they inhibit DNA methylation, providing a rationale for their use as epigenetic regulators and cell proliferation inhibitors. The underlying mechanisms are outlined, key supporting data presented, followed by brief mention of recent mathematical modeling supporting the general superiority of combination therapy. Several novel examples involving folate antagonists are proposed. PMID:26433846

  2. Histone Deacetylase Inhibitors for Cutaneous T-Cell Lymphoma.

    PubMed

    Duvic, Madeleine

    2015-10-01

    Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin's T-cell lymphomas that present as skin lesions. Mycosis fungoides with large cell transformation has a 5-year overall survival of 32% with involved skin and 7% with extracutaneous involvement. Failure to cure advanced MF with large cell transformation and peripheral T-cell lymphoma has resulted in a search for novel targeted agents including antibodies and gene modulators. Histone deacetylase inhibitors are small molecules that seem to be particularly active for T-cell lymphoma. PMID:26433847

  3. 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

  4. Identification of geographic clustering and regions spared by the Cutaneous T-Cell Lymphoma (CTCL) in Texas using two distinct cancer registries

    PubMed Central

    Litvinov, Ivan V.; Tetzlaff, Michael T.; Rahme, Elham; Habel, Youssef; Risser, David R.; Gangar, Pamela; Jennings, Michelle A.; Pehr, Kevin; Prieto, Victor G.; Sasseville, Denis; Duvic, Madeleine

    2015-01-01

    Background Cutaneous T-Cell Lymphomas (Mycosis Fungoides and its leukemic variant, Sézary Syndrome) are rare malignancies. Reports of occurrence of Mycosis Fungoides in married couples and families raise the possibility of an environmental trigger for this cancer. While it was suggested that CTLC arises from inappropriate T cell stimulation, currently no preventable trigger has been identified. Methods We analyzed by region, zip code, age, sex and ethnicity the demographic data of 1047 patients from Texas, who were seen in a CTCL clinic at the MD Anderson Cancer Center during 2000-2012 (the MDACC database) and 1990 patients that were recorded in the population-based Texas Cancer Registry (TCR) between 1996-2010. Subsequently data from both databases was cross analyzed and compared. Results Our findings, based on the MDACC database, document geographic clustering of patients in three communities within the Houston metropolitan area, where CTCL incidence rates were 5-20 times higher than the expected population rate. Analysis of the TCR database defined the CTCL population rate for the state to be 5.8 [95% CI 5.5, 6.0] cases per million individuals per year, confirmed the observations from the MDACC database and further highlighted additional areas of geographic clustering and regions spared by CTCL in Texas. Conclusions Our study documents geographic clustering of CTCL cases in Texas and argues for the existence of yet unknown external causes/triggers for this rare malignancy. PMID:25728286

  5. Twelve cases of Ki-1 positive anaplastic large cell lymphoma of skin.

    PubMed Central

    Banerjee, S S; Heald, J; Harris, M

    1991-01-01

    In seven of 12 cases of Ber-H2 (Ki-1) positive anaplastic large cell non-Hodgkin's lymphoma (Ki-1 ALCL) disease remained localised to skin, and in five there was extracutaneous spread. Four patients had histological evidence of pre-existing or coexisting mycosis fungoides, and three patients had a long standing history of eczema or ichthyosis. In two cases the presence of a T phenotype was shown in frozen sections, and in a further six cases a T phenotype was firmly established in paraffin wax sections. Four patients died less than one year after presentation (two with disseminated lymphoma; two from other causes); one died at five years with widespread lymphoma and the remaining seven cases were alive one to 14 1/2 years after presentation. Three of the four patients with associated mycosis fungoides had prolonged survival, contrary to the findings of previous reports which suggest secondary Ki-1 ALCL behaves aggressively. The recognition of these tumours is important because of their relatively good prognosis. The diagnosis can be readily substantiated immunohistochemically, using a simple panel of antibodies. Images PMID:1650796

  6. 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

  7. Primary Cutaneous Peripheral T-Cell Lymphoma Not Otherwise Specified: A Rapidly Progressive Variant of Cutaneous T-Cell Lymphoma

    PubMed Central

    Aderhold, Kimberly; Carpenter, Lisa; Brown, Krysta; Donato, Anthony

    2015-01-01

    Primary Cutaneous Peripheral T-Cell Lymphoma NOS (PTL-NOS) is a rare, progressive, fatal dermatologic disease that presents with features similar to many common benign plaque-like skin conditions, making recognition of its distinguishing features critical for early diagnosis and treatment (Bolognia et al., 2008). A 78-year-old woman presented to ambulatory care with a single 5 cm nodule on her shoulder that had developed rapidly over 1-2 weeks. Examination was suspicious for malignancy and a biopsy was performed. Biopsy results demonstrated CD4 positivity, consistent with Mycosis Fungoides with coexpression of CD5, CD47, and CD7. Within three months her cancer had progressed into diffuse lesions spanning her entire body. As rapid progression is usually uncharacteristic of Mycosis Fungoides, her diagnosis was amended to PTL-NOS. Cutaneous T-Cell Lymphoma (CTCL) should be suspected in patients with patches, plaques, erythroderma, or papules that persist or multiply despite conservative treatment. Singular biopsies are often nondiagnostic, requiring a high degree of suspicion if there is deviation from the anticipated clinical course. Multiple biopsies are often necessary to make the diagnosis. Physicians caring for patients with rapidly progressive, nonspecific dermatoses with features described above should keep more uncommon forms of CTCL in mind and refer for early biopsy. PMID:26380134

  8. Primary Cutaneous Peripheral T-Cell Lymphoma Not Otherwise Specified: A Rapidly Progressive Variant of Cutaneous T-Cell Lymphoma.

    PubMed

    Aderhold, Kimberly; Carpenter, Lisa; Brown, Krysta; Donato, Anthony

    2015-01-01

    Primary Cutaneous Peripheral T-Cell Lymphoma NOS (PTL-NOS) is a rare, progressive, fatal dermatologic disease that presents with features similar to many common benign plaque-like skin conditions, making recognition of its distinguishing features critical for early diagnosis and treatment (Bolognia et al., 2008). A 78-year-old woman presented to ambulatory care with a single 5 cm nodule on her shoulder that had developed rapidly over 1-2 weeks. Examination was suspicious for malignancy and a biopsy was performed. Biopsy results demonstrated CD4 positivity, consistent with Mycosis Fungoides with coexpression of CD5, CD47, and CD7. Within three months her cancer had progressed into diffuse lesions spanning her entire body. As rapid progression is usually uncharacteristic of Mycosis Fungoides, her diagnosis was amended to PTL-NOS. Cutaneous T-Cell Lymphoma (CTCL) should be suspected in patients with patches, plaques, erythroderma, or papules that persist or multiply despite conservative treatment. Singular biopsies are often nondiagnostic, requiring a high degree of suspicion if there is deviation from the anticipated clinical course. Multiple biopsies are often necessary to make the diagnosis. Physicians caring for patients with rapidly progressive, nonspecific dermatoses with features described above should keep more uncommon forms of CTCL in mind and refer for early biopsy. PMID:26380134

  9. [Angiogenesis and lymphangiogenesis in primary cutaneous T-cell lymphomas].

    PubMed

    Jankowska-Konsur, Alina; Kobierzycki, Christopher; Dzięgiel, Piotr

    2015-01-01

    Primary cutaneous T-cell lymphomas are a group of rare hematologic malignancies, derived from mature T lymphocytes and initially developing only in the skin. The most common lymphomas representing this group are mycosis fungoides and Sezary syndrome. Mycosis fungoides is an indolent disease with a chronic course and characteristic evolution of the skin lesions from erythematous patches, through plaques to tumors. Sezary syndrome is characterized by an aggressive course and a triad of symptoms (erythroderma, generalized lymphadenopathy, and the presence of atypical cells in the skin, lymph nodes and peripheral blood). The etiopathogenesis of cutaneous lymphomas is not fully understood, but a few studies on angiogenesis and lymphangiogenesis in these malignancies indicate a significant role in their development and progression. Angiogenesis is a process of formation of new blood vessels from existing ones. Lymphangiogenesis is a similar process concerning lymphatic vasculature. Development of new vessels is a complex process composed of several successive stages: migration, proliferation, and differentiation of endothelial cells, extracellular matrix degradation and formation and stabilization of new vessels, regulated by growth factors, cytokines and other proteins. Both phenomena are essential in the development and progression of solid tumors and hematological malignancies. Therapeutic strategies involving the inhibition of tumor angiogenesis and lymphangiogenesis are a promising new direction of studies in antitumor therapy, requiring further experiments. PMID:26561847

  10. 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

  11. 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

  12. 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

  13. Tacrolimus and Mycophenolate Mofetil in Preventing Graft-Versus-Host Disease in Patients Who Have Undergone Total-Body Irradiation With or Without Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant for Hematologic Cancer

    ClinicalTrials.gov

    2016-01-25

    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; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; 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 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 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. Long-term outcome after superficial keratectomy in an infant with epidermolysis bullosa.

    PubMed

    Chaurasia, Sunita; Ramappa, Muralidhar; Mishra, Dilip

    2016-06-01

    A 5-month-old boy presented with a congenital whitish raised lesion in the central cornea of the left eye. The child had a tendency to develop bullous eruptions on the skin with trivial trauma. The patient's father had a similar history of skin lesions. Because the lesion was in the central visual axis, a superficial anterior keratectomy with an amniotic membrane grafting was performed. The lesion healed well, restoring the corneal transparency and resulting in good visual acuity. When the boy was 4 years of age, his cornea was clear, and best-corrected visual acuity in the left eye was 20/60. There was no recurrence of the lesion. PMID:27108844

  4. Conservative treatment of a patient with epidermolysis bullosa presenting as bart syndrome: a case report.

    PubMed

    Kuvat, Samet Vasfi; Bozkurt, Mehmet

    2010-01-01

    We presented a case of a newborn male with aplasia cutis congenita on the lower limb. The case was treated with conservative method. As for the conservative treatment, daily hydrodebridement with 1/200 diluted povidone-iodine and serum physiologic was performed, followed by closure of the wound with a dexpanthenol + chlorhexidine + fusidic acid-impregnated sterile gauze bandage. the followup that occured after three weeks, the wound was completely epithelialized, but a hypopigmented scar remained in the limb. PMID:20490278

  5. Phototherapy and vitamin D.

    PubMed

    Juzeniene, Asta; Grigalavicius, Mantas; Juraleviciute, Marina; Grant, William B

    2016-01-01

    The skin is the site for the photosynthesis of vitamin D and is a target tissue for the active metabolite of vitamin D. An increasing body of evidence indicates that vitamin D produced during phototherapy may be responsible for the positive effects observed during treatment of some skin diseases. Topical or oral application of vitamin D derivatives are used alone or with phototherapy. This paper reviews what is known about the use of phototherapy to enhance vitamin D levels, the use of vitamin D analogues with phototherapy, the efficacy of combination therapies, and controversies regarding some of the outcomes. Vitamin D can play a beneficial role in treating psoriasis, even though the exact role of vitamin D in the pathogenesis and severity of psoriasis remains unclear. The role of vitamin D in vitiligo, atopic dermatitis, polymorphic light eruption, and mycosis fungoides must be further investigated. PMID:27638432

  6. 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.

  7. 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

  8. Diagnosis, prognosis and management of erythrodermic cutaneous T-cell lymphoma.

    PubMed

    Moriarty, Bláithín; Whittaker, Sean

    2015-04-01

    Erythroderma describes complete or near-complete skin surface erythema of any cause. Cutaneous T-cell lymphoma accounts for a minority of cases of erythroderma and consists of erythrodermic mycosis fungoides, Sézary syndrome. Both adult T-cell leukemia/lymphoma and T-cell prolymphocytic leukemia can also rarely present with erythroderma. Diagnosis may be extremely challenging because benign disorders may have overlapping features with those of lymphoma. Prognosis is poor with median survival of approximately 2 years. The evidence base for therapeutic approaches relies on cohorts and case series and more recently Phase II trials. Improved patient selection and identification of appropriate conditioning regimens for reduced intensity allogeneic hematopoetic transplant are likely to improve survival, although a significant number of patients may not be fit for transplant because of advanced age and comorbidities.

  9. p53 immunoreactivity is uncommon in primary cutaneous lymphoma.

    PubMed

    McGregor, J M; Dublin, E A; Levison, D A; MacDonald, D M; Smith, N P; Whittaker, S

    1995-03-01

    p53 gene mutation appears to play an important role in the development of systemic lymphoma, and may be associated with tumour progression. Its role in cutaneous lymphoma is currently unknown. We examined p53 expression in 55 biopsies of cutaneous lymphoma, including patch-, plaque- and tumour-stage mycosis fungoides (MF), T- and B-cell lymphoma and lymphomatoid papulosis. Strong, homogeneous p53 expression, thought to correlate most closely with p53 gene mutation, was seen in only three cases; in a plaque and tumour from a patient with tumour-stage MF, in plaque-stage MF in a patient without tumours, and in one case of CD30+ large-cell anaplastic lymphoma. These data suggest that p53 gene mutation is not a critical step in the development of the majority of primary cutaneous lymphomas.

  10. Molecular genetics of cutaneous lymphomas.

    PubMed

    Whittaker, S

    2001-09-01

    The underlying molecular basis of primary cutaneous lymphomas has not yet been clarified. However, abnormalities of cell cycle control genes and well-defined tumor suppressor genes such as p53 are common and may contribute to disease progression and treatment resistance. Biallelic inactivation of tumor suppressor genes usually occurs by a combination of deletion, point mutation, and/or promotor hypermethylation. The detection of UVB-specific mutations of p53 requires confirmation but may have important implications for the management of patients with mycosis fungoides. Molecular cytogenetic studies have identified common regions of chromosomal deletion and amplification, which suggests the presence and location of genes that are of critical importance in the pathogenesis of cutaneous lymphoma.

  11. 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

  12. Cutaneous necrotizing vasculitis. Relation to systemic disease.

    PubMed

    Lotti, T M; Comacchi, C; Ghersetich, I

    1999-01-01

    Cutaneous necrotizing vasculitis (CNV) is a complex multisystem disease generally involving the skin and mucous membranes, often accompanied by renal, gastrointestinal, pericardial, neurological, and articular signs and symptoms. CNV may be idiopatical or occur in association with a drug, infection, or underlying disease. CNV has been shown in patients with chronic infections (viral, bacterial, protozoa, helminthic), serum sickness, a variety of collagen vascular diseases (systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, Behçet's disease) hyperglobulinemic states, cryoglobulinemia, bowel bypass syndrome, ulcerative colitis, cystic fibrosis, primary biliary cirrhosis and HIV infection. Association with malignancies is not frequent. Lymphoproliferative disorders (Hodgkin's disease, mycosis fungoides, lymphosarcoma, adult T-cell leukemia, multiple mieloma) and solid tumors (lung cancer, colon carcinoma, renal, prostate, head and neck cancer and breast cancer) may be associated with CNV. Whenever possible, treatment is directed at the elimination of the cause. In other cases after adequate laboratory screening local and systemic therapy are recommended. PMID:10599332

  13. 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

  14. Recommendations for Radiotherapy Technique and Dose in Extra-nodal Lymphoma.

    PubMed

    Hoskin, P J; Díez, P; Gallop-Evans, E; Syndikus, I; Bates, A; Bayne, M

    2016-01-01

    Extra-nodal sites may be involved in around 40% of patients with non-Hodgkin lymphoma. The general principles for target volume delineation in this setting are presented, together with specific examples. In general, the entire organ affected should be encompassed in the clinical target volume with an expansion of at least 10 mm, increased in some instances to account for patterns of potential lymphatic flow. Adjacent lymph nodes may be treated using standard techniques for nodal irradiation. Doses for extra-nodal lymphoma follow the same principles as nodal lymphoma, delivering 30 Gy in 15 fractions for Hodgkin and aggressive non-Hodgkin lymphoma and 24 Gy in 12 fractions for indolent lymphomas, with the exception of certain palliative situations, mycosis fungoides, central nervous system lymphoma and natural killer/T-cell lymphoma.

  15. Transformation of Sézary syndrome into CD30+ anaplastic large T-cell lymphoma after alemtuzumab therapy with evidence of clonal unity.

    PubMed

    Nevet, Mariela Judith; Zuckerman, Tsila; Sahar, Dvora; Bergman, Reuven

    2015-01-01

    Alemtuzumab is a humanized mouse antibody targeting the CD52 cell surface, which has been effective in patients with advanced stage mycosis fungoides (MF) including erythrodermic MF and Sézary syndrome. There are a few descriptions of large cell transformation after its administration. A young patient with an acute onset of Sézary syndrome treated initially unsuccessfully with fludarabine and cyclophosphamide and later on successfully with alemtuzumab has been described. Three weeks after the beginning of therapy, however, she developed transformed T-cell lymphoma indistinguishable from CD30 anaplastic large-cell lymphoma. After bone marrow transplantation, the transformed CD30 cutaneous T-cell lymphoma recurred as a transformed CD30 plaque MF. All 3 types of lesions showed the same T-cell receptor clonal gene rearrangement, which supports the notion that Sézary syndrome, CD30 anaplastic large-cell lymphoma, and MF are interrelated.

  16. 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

  17. CPI-613, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-08-12

    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

  18. 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

  19. Flavopiridol in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

    ClinicalTrials.gov

    2016-06-27

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin 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 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 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; Splenic Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Waldenström Macroglobulinemia

  20. 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

  1. Romidepsin for cutaneous T-cell lymphoma.

    PubMed

    Prince, H Miles; Dickinson, Michael

    2012-07-01

    Cutaneous T-cell lymphomas (CTCL) are relatively rare lymphomas with an annual incidence of approximately 0.2 to 0.8/100,000 and comprise a variety of clinical entities; mycosis fungoides or its leukemic variant Sezary syndrome account for the majority of cases. Advanced-stage disease is typically treated with bexarotene (a retinoid), interferon, or conventional chemotherapeutic agents, but relapses are inevitable. Histone deacetylase inhibitors, which modify the epigenome, are an attractive addition to the armamentarium. On the basis of 2 large phase II studies, the U.S. Food and Drug Administration approved intravenous romidepsin for patients with relapsed and/or refractory CTCL. Romidepsin provides a subset of patients with an opportunity for prolonged clinical responses with a tolerable side effect profile.

  2. Skin Cancer in Black Americans: A Review of 126 Cases

    PubMed Central

    Bang, Ki Moon; Halder, Rebat M.; White, Jack E.; Sampson, Calvin C.; Wilson, Jerome

    1987-01-01

    Primary cancer of the skin is rare in blacks. The records of 126 black patients with skin cancer were reviewed. Histopathologic findings included squamous cell carcinomas (43) basal cell carcinomas (39) malignant melanomas (8) dermatofibrosarcomas (16) Bowen's disease (6) mycosis fungoides (14) and sebaceous cell carcinoma (1). There is a higher percentage of skin cancer involving covered areas in blacks than among whites. Squamous cell carcinoma was the most common skin cancer in blacks. The distribution of basal cell carcinoma in blacks was 30 percent in this series, as compared with 80 percent in whites in the 1977 to 1978 survey. The majority of patients with squamous cell carcinoma had associated predisposing conditions and lesions on non-sun-exposed skin. Sunlight and occupational chemical exposure did not appear to be associated with skin cancer in blacks in this series. ImagesFigure 1Figure 2 PMID:3820333

  3. Malignant lymphomas of the skin: their differentiation from lymphoid and nonlymphoid cutaneous infiltrates that simulate lymphoma.

    PubMed

    Burke, J S

    1985-08-01

    Malignant lymphomas of the skin, excluding mycosis fungoides, are pathologically, immunologically, and clinically heterogeneous. Varying patterns and degrees of cutaneous infiltration are encountered in all histologic subtypes of non-Hodgkin's lymphomas. Immunologic studies have shown relatively equal numbers of cases with B and T cell phenotypes, but true histiocytic lymphomas of the skin also occur. Patients may be of any age, and they may have lymphoma in any clinical stage. A low clinical stage and a low-grade histologic subtype are significant factors for long survival. The differential diagnosis includes a variety of lymphoid infiltrates that are referred to as a group as cutaneous lymphoid hyperplasia; it also includes lymphomatoid papulosis as well as nonlymphoid cutaneous infiltrates such as myeloid leukemias, histiocytosis X, malignant histiocytosis, regressing atypical histiocytosis, and neuroendocrine (Merkel) cell carcinoma. Distinction of cutaneous lymphomas from these entities requires comprehension of multiple variables, including immunologic as well as morphologic and clinical factors.

  4. Consistency and distribution of reflectance confocal microscopy features for diagnosis of cutaneous T cell lymphoma

    NASA Astrophysics Data System (ADS)

    Lange-Asschenfeldt, Susanne; Babilli, Jasmin; Beyer, Marc; Ríus-Diaz, Francisca; González, Salvador; Stockfleth, Eggert; Ulrich, Martina

    2012-01-01

    Reflectance confocal microscopy (RCM) represents a noninvasive imaging technique that has previously been used for characterization of mycosis fungoides (MF) in a pilot study. We aimed to test the applicability of RCM for diagnosis and differential diagnosis of MF in a clinical study. A total of 39 test sites of 15 patients with a biopsy-proven diagnosis of either MF, parapsoriasis, Sézary syndrome, or lymphomatoid papulosis were analyzed for presence and absence of RCM features of MF. Cochran and Chi2 analysis were applied to test the concordance between investigators and the distribution of RCM features, respectively. For selected parameters, the Cochran analysis showed good concordance between investigators. Inter-observer reproducibility was highest for junctional atypical lymphocytes, architectural disarray, and spongiosis. Similarly, Chi2 analysis demonstrated that selected features were present at particularly high frequency in individual skin diseases, with values ranging from 73% to 100% of all examined cases.

  5. 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.

  6. [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

  7. 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

  8. Recommendations for Radiotherapy Technique and Dose in Extra-nodal Lymphoma.

    PubMed

    Hoskin, P J; Díez, P; Gallop-Evans, E; Syndikus, I; Bates, A; Bayne, M

    2016-01-01

    Extra-nodal sites may be involved in around 40% of patients with non-Hodgkin lymphoma. The general principles for target volume delineation in this setting are presented, together with specific examples. In general, the entire organ affected should be encompassed in the clinical target volume with an expansion of at least 10 mm, increased in some instances to account for patterns of potential lymphatic flow. Adjacent lymph nodes may be treated using standard techniques for nodal irradiation. Doses for extra-nodal lymphoma follow the same principles as nodal lymphoma, delivering 30 Gy in 15 fractions for Hodgkin and aggressive non-Hodgkin lymphoma and 24 Gy in 12 fractions for indolent lymphomas, with the exception of certain palliative situations, mycosis fungoides, central nervous system lymphoma and natural killer/T-cell lymphoma. PMID:26456507

  9. Evaluation, Diagnosis, and Staging of Cutaneous Lymphoma.

    PubMed

    Olsen, Elise A

    2015-10-01

    Primary cutaneous lymphomas (PCLs) are an extremely heterogeneous group of non-Hodgkin lymphomas that manifest in the skin. Their diagnosis is complex and based on clinical lesion type and evaluation of findings on light microscopic examination, immunohistochemistry and molecular analysis of representative skin biopsies. The evaluation, classification, and staging system is unique for mycosis fungoides (MF) and Sézary syndrome (SS), the most common subtypes of cutaneous T-cell lymphoma (CTCL) versus the other subtypes of Non-MF/Non-SS CTCL and the subtypes of cutaneous B-cell lymphoma (CBCL). Since current treatment is stage-based, it is particularly important that the correct diagnosis and stage be ascertained initially. The purpose of this article is to review the current evaluation, diagnosis, classification, staging, assessment techniques, and response criteria for the various types of both T-cell and B-cell PCLs. PMID:26433839

  10. Lymphomatoid contact dermatitis associated with textile dye at an unusual location.

    PubMed

    Uzunçakmak, Tuğba Kevser; Akdeniz, Necmettin; Özkanlı, Şeyma; Türkoğlu, Zafer; Zemheri, Ebru Itır; Ka Radağ, Ayşe Serap

    2015-12-01

    Lymphomatoid contact dermatitis (LCD) is a rare variant of noneczematous allergic contact dermatitis, which can mimick parapsoriasis or early-stage mycosis fungoides with its atypical clinical and histopathological manifestation. Many different haptens have been reported to be associated with this reaction. Histopathological examination, immunhistochemistry, clonality tests, and patch tests are mandatory for diagnosis and differential diagnosis. We present a 48-year-old male with a four years history of a relapsing erythematous plaque on the glans penis. Topical corticosteroids had been prescribed but he complained of relapse upon withdrawal. Histopathological examination was consistent with LCD. Thin layer rapid use epicutaneous patch test result was (++) for disperse blue and nickel sulfate. We present this case because of its rarity and unusual localization. This kind of allergic contact dermatitis should be remembered in differential diagnosis of nonspesific pruritic plaques over the genital region. PMID:26904444

  11. Lymphomatoid contact dermatitis associated with textile dye at an unusual location

    PubMed Central

    Uzunçakmak, Tuğba Kevser; Akdeniz, Necmettin; Özkanlı, Şeyma; Türkoğlu, Zafer; Zemheri, Ebru Itır; Ka Radağ, Ayşe Serap

    2015-01-01

    Lymphomatoid contact dermatitis (LCD) is a rare variant of noneczematous allergic contact dermatitis, which can mimick parapsoriasis or early-stage mycosis fungoides with its atypical clinical and histopathological manifestation. Many different haptens have been reported to be associated with this reaction. Histopathological examination, immunhistochemistry, clonality tests, and patch tests are mandatory for diagnosis and differential diagnosis. We present a 48-year-old male with a four years history of a relapsing erythematous plaque on the glans penis. Topical corticosteroids had been prescribed but he complained of relapse upon withdrawal. Histopathological examination was consistent with LCD. Thin layer rapid use epicutaneous patch test result was (++) for disperse blue and nickel sulfate. We present this case because of its rarity and unusual localization. This kind of allergic contact dermatitis should be remembered in differential diagnosis of nonspesific pruritic plaques over the genital region. PMID:26904444

  12. The skin as a target organ in multisystemic diseases II.

    PubMed

    Tsankov, Nikolai; Kazandjieva, Jana; Darlenski, Razvigor

    2015-01-01

    Progress in medical science has given a new reading to the claim that the skin could be a mirror of the pathological changes found in the internal organs. The concept that we previously promoted is furthered in this issue; namely that the greatest part of skin diseases are systemic ones. In this issue we focus on another group of diseases with systemic involvement and skin manifestations. We review such inflammatory conditions as lichen planus, autoinflammatory syndromes, and pyoderma gangrenosum focusing on their systemic involvement. We have not missed such classic examples of systemic involvement as scleroderma. In this issue we have included two infectious diseases with multi-organ involvement: Lyme disease and Herpes simplex. In contrast to our previous work, we have also addressed neoplastic diseases - namely mycosis fungoides. PMID:26321395

  13. Clinical Practice Guidelines for Cutaneous Lymphomas.

    PubMed

    Sutton, Angela M; Hurley, M Yadira

    2015-01-01

    Primary cutaneous lymphomas are non-Hodgkin lymphomas, which are broadly divided into cutaneous T-cell lymphomas and cutaneous B-cell lymphomas. These classifications include numerous distinct entities, all with varying clinical presentations and disease courses. Herein, we will review the cutaneous T-cell lymphomas, including Mycosis Fungoides, Sézary syndrome, CD30+ lymphoproliferative disorders, as well as other less common entities. Cutaneous B-cell lymphomas will also be discussed, including primary cutaneous marginal zoned lymphoma, cutaneous follicle-center lymphoma, diffuse large B-cell lymphoma, leg type, as well as other less common entities. Accurate and early diagnosis is key, as the treatment and prognosis varies significantly between conditions. PMID:26455060

  14. Primary cutaneous T-cell lymphomas: a review.

    PubMed

    Sidiropoulos, Konstantinos G; Martinez-Escala, M Estela; Yelamos, Oriol; Guitart, Joan; Sidiropoulos, Michael

    2015-12-01

    Primary cutaneous T-cell lymphomas (CTCLs) represent a number of extranodal lymphomas arising from a malignant population of lymphocytes in the skin, with the most common type being mycosis fungoides (MF) representing half of all primary CTCLs. Despite advances in immunohistochemistry and molecular methodology, significant diagnostic challenges remain due to phenotypic overlap of primary CTCLs with several inflammatory dermatoses, secondary lymphomas, among other conditions. Clinical features such as presentation and morphology, staging, histology, immunophenotype and molecular features must be considered in detail before a diagnosis is made in order to minimise false-positive, false-negative and indeterminate diagnoses. Herein, we review primary CTCLs, including epidemiological data, a brief summary of clinical presentations, immunophenotype, molecular signatures and differential diagnoses. PMID:26602417

  15. Cutaneous T cell Lymphoma: an Update on Pathogenesis and Systemic Therapy.

    PubMed

    Chung, Catherine G; Poligone, Brian

    2015-12-01

    Mycosis fungoides (MF) and its leukemic variant, Sézary syndrome (SS), are malignancies of skin-homing T cells that comprise the majority of cutaneous T cell lymphomas (CTCL). Treatment of CTCL is limited and can be approached by skin-directed therapy or systemic therapy. Recent investigations into the pathogenesis of MF and SS have broadened the therapeutic targets; here, we review emerging concepts in the pathogenesis of MF and SS as well as novel and traditional systemic therapies for MF and SS. These include histone deacetylase inhibitors (vorinostat, romidepsin, panobinostat, and belinostat), monoclonal antibodies (alemtuzumab, brentuximab vedotin, and mogamulizumab) and single-agent cytotoxic chemotherapeutic agents (e.g., pralatrexate, doxorubicin, bendamustine, and forodesine), as well as multi-agent chemotherapy regimens. PMID:26626770

  16. A Rare Presentation of Transformed, CD30(+) High-Grade Cutaneous T-Cell Lymphoma of the Hallux A Case Report.

    PubMed

    McCartan, Brant L; Tang, Bang; Berglund, Allyson; Giurini, John; Pihan, German

    2015-11-01

    Cutaneous T-cell lymphoma is a type of non-Hodgkin's lymphoma, which is a neoplasm affecting the lymphatic system. Mycosis fungoides is the most common subset of cutaneous T-cell lymphoma and is often treated conservatively. This neoplasm is most common in adults older than 60 years and does not regularly manifest in the toes. A case is reported of a 70-year-old man seen for a nonhealing hallux ulceration leading to amputation. Histopathologic examination revealed a rare transformed CD30(+) high-grade cutaneous T-cell lymphoma. The morbidity of lymphomas is highly dependent on type and grade. Pharmaceutical precision therapies exist that target specific molecular defects or abnormally expressed genes, such as high expression of CD30. This article focuses on treatment protocol and emphasizes the importance of early diagnosis, determination of cell type, and proper referral of atypical dermatologic lesions. PMID:26667508

  17. Practical Management of CD30⁺ Lymphoproliferative Disorders.

    PubMed

    Hughey, Lauren C

    2015-10-01

    Primary cutaneous CD30⁺ lymphoproliferative disorders (LPDs) account for approximately 25% of cutaneous lymphomas. Although these LPDs are clinically heterogeneous, they can be indistinguishable histologically. Lymphomatoid papulosis rarely requires systemic treatment; however, multifocal primary cutaneous anaplastic large cell cutaneous lymphoma and large cell transformation of mycosis fungoides are typically treated systemically. As CD30⁺ LPDs are rare, there is little published evidence to support a specific treatment algorithm. Most studies are case reports, small case series, or retrospective reviews. This article discusses various treatment choices for each of the CD30⁺ disorders and offers practical pearls to aid in choosing an appropriate regimen. PMID:26433852

  18. Diagnosis, prognosis and management of erythrodermic cutaneous T-cell lymphoma.

    PubMed

    Moriarty, Bláithín; Whittaker, Sean

    2015-04-01

    Erythroderma describes complete or near-complete skin surface erythema of any cause. Cutaneous T-cell lymphoma accounts for a minority of cases of erythroderma and consists of erythrodermic mycosis fungoides, Sézary syndrome. Both adult T-cell leukemia/lymphoma and T-cell prolymphocytic leukemia can also rarely present with erythroderma. Diagnosis may be extremely challenging because benign disorders may have overlapping features with those of lymphoma. Prognosis is poor with median survival of approximately 2 years. The evidence base for therapeutic approaches relies on cohorts and case series and more recently Phase II trials. Improved patient selection and identification of appropriate conditioning regimens for reduced intensity allogeneic hematopoetic transplant are likely to improve survival, although a significant number of patients may not be fit for transplant because of advanced age and comorbidities. PMID:25495961

  19. 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

  20. Skin diseases following a Christmas tree pattern.

    PubMed

    Wollenberg, Andreas; Eames, Tatiana

    2011-01-01

    Pattern analysis of skin lesions is an art and a key competence of every dermatologist. Three major line patterns cover the human body-the dermatomes or Head zones, the nevoid lines of Blaschko, and the relaxed skin tension lines, or Langer lines. Head zones represent skin areas innervated from the same sensory neuronal segment or spinal nerve zone. Blaschko lines are borderlines of epidermal aberration caused by genetic mosaicism occurring in the early stages of embryogenesis. Langer lines show the direction of the lowest naturally occurring skin tension, and its thoracodorsal manifestation is the Christmas tree pattern. Here we review clinical aspects of pityriasis rosea, mycosis fungoides, stage 2 syphilis, exanthematic Kaposi sarcoma, exanthematic psoriasis, Leser-Trelat syndrome, and other primary skin diseases with a Christmas tree pattern. Secondary skin diseases, such as herpes zoster or indeterminate cell histiocytosis, may follow this pattern if they are linked to a primary skin disease by the Wolf isotopic response.