[Molecular genetics and the skin: genes or pleasure?].
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Biomedical subjects
Publications and source records attributed to O Dereure.
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INTRODUCTION: alpha-Interferon is associated with numerous cutaneous side effects, but the accurate incidence of these complications is not clearly known. OBJECTIVES: A prospective study was designed to evaluate the incidence and clinical pattern of cutaneous side effects in a cohort of patients receiving adjuvant therapy with low-dose interferon for malignant melanoma. MATERIAL AND METHODS: A cohort of 33 patients with stage IIA and IIB melanoma treated with low-dose alpha-interferon (3 MIU 3 times a week for 18 months) were prospectively enrolled in a single-center study. The patients responded to a questionnaire on their medical history and were systematically examined for any cutaneous lesions before treatment and every 3 months afterwards. RESULTS: 29/33 patients (87%) experienced 1 or more cutaneous side effects. The most frequent was hair loss and occurred in 16 cases (48.4%). Hair discoloration was noted in 6 cases (18%). Eczematous reactions at injection sites or at remote sites were observed in 13 patients (39%). Pruritus occurred in 10 cases (30%). Xerostomia, Raynaud's phenomenon or livedo reticularis were observed in 10 patients, associated with an increase in circulating autoantibody titer in 2 cases. Some rare side effects were observed: urticaria (1 case) or angioedema (1 case), worsening of preexisting seborrheic dermatitis (3 cases), herpetic recurrence (2 cases), pityriasis versicolor (1 case), worsening of recurrent buccal aphthous ulcer (1 case) and vitiligo (1 case). CONCLUSION: Cutaneous adverse events during adjuvant immunotherapy of melanoma with low-dose alpha-interferon seem to be frequent but do not result in treatment discontinuation. A good awareness of these side effects may be useful for a more accurate survey and clinical management of patients receiving this treatment.
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BACKGROUND: The presence of a significant percentage of circulating atypical lymphocytes in peripheral blood has already been demonstrated in systemic CD30+ anaplastic large cell lymphoma (ALCL), which implies that a leukaemic component may be present in this subset of lymphomas. However, no similar data are available for the cutaneous counterpart of this particular lymphoproliferation. OBJECTIVES: To assess the presence of atypical cells, CD30+ lymphocytes and of a dominant T-cell clone in peripheral blood in a series of patients with cutaneous CD30+ ALCL. MATERIALS AND METHODS: Nine patients with either primary (four) or secondary (five) cutaneous CD4+ CD30+ ALCL were selected. The percentage of CD30+ CD4+ lymphocytes among peripheral blood mononuclear cells (PBMC) was determined by flow cytometry and the presence of a dominant circulating T-cell clone was assessed by polymerase chain reaction targeting the T-cell receptor gamma chain. A control group composed of apparently healthy individuals was similarly studied at the same time. RESULTS: The mean percentage of CD30+ cells in PBMC was slightly higher in patients than in controls (3.9% vs. 2.7%) but the difference was not statistically significant. Only two patients displayed more than 5% CD30+ cells, both of whom had a minor tumour burden. A dominant circulating T-cell clone was detected in only three cases, including these two latter patients. CONCLUSIONS: The occurrence of a significant percentage of CD30+ CD4+ circulating cells is rare in active cutaneous CD30+ ALCL, either primary or secondary. This percentage is not related to the apparent skin tumour burden but a significant figure appeared to be correlated with the detection of a dominant T-cell clone in peripheral blood. Overall, these data show that, unlike mycosis fungoides, peripheral blood involvement seems infrequent in cutaneous CD30+ ALCL. The hypothesis that a high percentage of CD30+ circulating cells might be related to the presence of a cryptic systemic disease cannot be ruled out.
Therapeutic monoclonal antibodies, soluble cytokines and receptors to cytokines, and inhibitors of tyrosine kinase, are currently used in an ever increasing number of patients with neoplastic and inflammatory disorders. Their cutaneous side effects are not always well known by physicians in charge of these new biotherapies. However, these side effects seem to be relatively frequent and may seriously disturb the patients or even represent a life-threatening event. Accordingly, it appears necessary for dermatologists and physicians using these therapies to be aware of the varied patterns of skin complications they may cause, in order to manage the treatment in the safest and most comfortable way for the patients.
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BACKGROUND: Cutaneous side-effects of treatment with interferon alfa or interferon alfa plus ribavirin in patients with hepatitis C have already been reported but they are mostly local with inflammation and, much less frequently, necrosis at the injection points. By contrast, very few data are available with regard to distant skin reactions, particularly inflammatory lesions on other parts of the body. OBJECTIVES: To assess the clinical and histological pattern of inflammatory skin lesions outside the injection points in patients treated with interferon alfa and ribavirin for chronic hepatitis C. METHODS: Twenty patients attending a University Hospital in Southern France (secondary referral centre) were evaluated regard to clinical history, type and localization of lesions, progression and histology. Skin testing was performed in some patients and the relevance of the results was evaluated. RESULTS: Eczema-like skin lesions were mainly distributed on the extremities, sometimes associated with photosensitivity. They usually occurred between 2 and 4 months of treatment. Histology was nonspecific, with a dermal, mainly perivascular, mononuclear infiltrate. Skin testing was poorly informative and was not predictive of relapse. Treatment had to be interrupted in half the patients, of whom two of three relapsed on resuming therapy. CONCLUSIONS: The incidence of inflammatory skin lesions at a distance from injection sites in patients treated with interferon alfa and ribavirin for chronic hepatitis C is currently unknown, but this adverse event must be taken into consideration as it may lead to the transient or definitive interruption of treatment.
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BACKGROUND: Limits of Wells'syndrome, a nosologically enlarged entity defined after classic eosinophilic cellulitis, are imprecise. We report on a new "frontier" case, remarkable in its clinical pattern and its high sensitivity to antimalarial drugs. CASE REPORT: A 35-year-old woman was referred for evaluation of recurrent inflammatory, figurated and often annular lesions, mainly located on the trunk and the proximal parts of the limbs, associated with significant peripheral eosinophilia and featuring dense perivascular infiltrates throughout the dermis with abundant eosinophils but without any "flame figure". These lesions responded dramatically to protracted treatment with hydroxychloroquine. DISCUSSION: The relationship of this affection to Wells' syndrome is discussed along with its possible similarities to the sparse reports of so-called eosinophilic annular erythema.
UNDERESTIMATED SIDE EFFECTS: Skin reactions to interferon (INF) treatment are uncommon in the larger series in the literature and are usually considered to be minor. They account for 5 to 12% of adverse effects to IFN and are encountered increasingly in patients with active chronic hepatitis C. Reactions may be local, occurring exclusively at the site of injection, or general. REPORTED EFFECTS AND TREATMENTS: We reviewed the literature on local skin reactions at the site of injection of the different interferons to study the underlying pathophysiological mechanisms and management schemes used. TWO TYPES OF REACTIONS: Local skin reactions can be divided into two types depending on the potential gravity and management. Minor reactions (transient erythema, eczema, depilation) have few clinical or therapeutic implications. More serious reactions, necrosis, vasculitis or injection can be potentially severe and require definitive interruption of treatment. PREVENTION: Preventive measures include careful education concerning self-injections using proper asepsia, variation of injection sites, and self-assessment of persistent skin reactions.
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