Meyerson's phenomenon induced by interferon-alfa plus ribavirin in hepatitis C infection.
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Biomedical subjects
Publications and source records attributed to J J Guilhou.
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BACKGROUND: Psoriasis is a common inflammatory skin disease characterized by uncontrolled proliferation of keratinocytes and recruitment of T lymphocytes into the skin. The possible role of human endogenous retroviruses (HERVs) in the induction of psoriasis has been suggested, based upon the previous observations of retrovirus-like particles in psoriasis from skin lesional plaques, urine and stimulated lymphocytes. OBJECTIVES: To investigate the expression of HERV-E transmembrane envelope glycoprotein (HERV-E env) in normal, psoriatic and atopic human skin, and to examine the influence of ultraviolet (UV) B irradiation on HERV-E env expression in normal human epidermal keratinocytes. METHODS: The analysis was performed on both skin biopsies and organotypic skin cultures using immunofluorescence and Western immunoblotting. UVB irradiation (312 nm) of cultured normal human keratinocytes was performed using a dose of 30 mJ cm(-2). RESULTS: Positive staining was observed in most of the psoriatic and atopic skin samples, whereas only 15% of the normal skin samples were faintly positive. In addition, the pattern of expression of HERV-E env differed markedly in psoriasis vs. atopy. By Western blotting analysis, two main proteins of 54 and 57 kDa were detected in extracts of normal skin, normal keratinocyte cultures and reconstructed epidermis from psoriatic and normal punch biopsies. An increased level of expression of these proteins was noted in extracts from psoriatic vs. normal reconstructed epidermis. The overexpression of the 57-kDa protein in normal human cultured keratinocytes was dramatically reduced by UVB irradiation. CONCLUSIONS: These data suggest for the first time that HERV-E env is expressed in normal and pathological human skin. Further studies are now required to elucidate the role of such viral proteins in the pathogenesis of psoriasis.
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.
BACKGROUND: A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris. OBJECTIVES: To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX. METHODS: Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well. RESULTS: The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3.4 mg week-1 (phase (II) and 2.6 mg week-1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle). CONCLUSIONS: The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased.
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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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BACKGROUND: Porphyria cutanea tarda (PCT) is associated in most cases with iron overload, which may participate in decreased activity of uroporphyrinogen decarboxylase in the liver. The aetiology of this iron overload remains unknown; however, it has been demonstrated that mutations of HFE, the genetic haemochromatosis gene, might be present in a significant proportion of Anglo-Saxon and Italian patients. Furthermore, transferrin receptor polymorphism may influence the affinity of this receptor to its ligand with a subsequent increase of cellular iron absorption and storage. OBJECTIVES: To evaluate the incidence and spectrum of HFE mutations and the relative frequency of the two main alleles of transferrin receptor in patients with PCT originating from southern France, and to evaluate the relationship of these genetic data with iron status, and with hepatitis B and C and human immunodeficiency virus (HIV) infections. METHODS: Thirty-six consecutive patients with either sporadic or familial PCT were prospectively included between 1997 and 2000. Search for the presence of the three main mutations of the HFE gene and identification of the transferrin receptor alleles were performed using polymerase chain reaction followed by enzymatic digestion. Iron parameters and viral status for hepatitis B and C viruses and HIV were determined. RESULTS: Seven patients (19%) showed heterozygous C282Y mutation, but no C282Y homozygote was present; five patients (14%) carried homozygous H63D mutation, while eight (22%) were heterozygous for this mutation. One patient was heterozygous for the S65C mutation (3%). Iron parameters demonstrated overload in all patients, without a clear difference between patients with and without deleterious mutations of the HFE gene. Infection by hepatitis C virus was documented in 20 patients (56%), and was significantly less frequent in patients with deleterious HFE mutations. The profile of transferrin receptor alleles in PCT patients did not show significant variation compared with the general population. CONCLUSIONS: This study confirms the high frequency of HFE mutations in patients with PCT and supports the hypothesis that HFE gene abnormalities might play a significant part in the PCT pathomechanism, probably through iron overload; by contrast, transferrin receptor polymorphisms do not appear to play a significant part in iron overload in PCT.
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Calcipotriol is a vitamin D derivative synthesized in 1985 by the Léo Laboratories. Its mode of action is identical to that of 1-25 vitamin D3 (calcitriol), essentially by regulating the activity of genes capable of responding to vitamin D. Calcipotriol leads to reduction in keratinocyte proliferation and induces their differentiation as well as having important immunomodulator functions. Toxicology studies have demonstrated that phosphorus calcium metabolism anomalies are only observed for doses above those recommended for clinical use (100 g per week). The half-life of Calcipotriol is much shorter than that of calcitriol and its metabolites are inactive. The effects of Calcipotriol on phosphorus calcium metabolism are much less pronounced than those of calcitriol. Therapeutic trials in psoriasis have demonstrated the superiority of Calcipotriol over its excipient, class 2 dermatocorticoids, and reducers. Given in combination with phototherapy, cyclosporin or retinoids, Calcipotriol provides more complete improvement in lesions and allows a reduction in the cumulative doses of these treatments. Calcipotriol is effective in certain keratinization disorders (ichtyoses) as well as in localized sclerodermia and vitiligo, although the effect is less certain for the latter conditions. At recommended doses, adverse effects are limited to skin reactions with lesional and perilesional irritation in about 20 p. 100 of the cases. Contact dermatitis is rare. Photosensitivization can be observed when Calcipotriol is applied in patients undergoing UVB phototherapy. The marketing approval in France includes indications for psoriasis not involving more than 40 p. 100 of the skin surface. Several studies have demonstrated the efficacy and safety of Calcipotriol in children using the dose of 50 g per week per m2 body surface area. Contraindications include hypercalcemia, pregnancy and nursing. Three formulations are available (salve, cream, and lotion, all at 0.005 p. 100 concentration) for different administration schemes: two applications per day, alternative applications with dermocorticoid or in combination with systemic treatment for psoriasis. Long-term treatment protocols have not been determined.
INTRODUCTION: Melanomas of unknown primary site are rare. To establish their diagnosis the metastatic nature of the lesion must be confirmed clinically and histologically, the melanoid nature by histology and immunohistochemistry. Any primary melanoma must be eliminated by careful examination of the skin and mucosa, and the absence of past surgical excision of skin lesions must be confirmed. We studied the epidemiological, clinic and prognostic characteristics of 19 melanomas of unknown primary site in a series of 646 melanomas. MATERIAL AND METHODS: This retrospective study was conducted on a series of 646 melanomas recruited over a period of 14 years. The epidemiological (age, gender, phototype and family history of melanoma), clinical and prognostic parameters (relapse and global survival rate) were analyzed in 19 patients. Clinical and epidemiological data were compared with the 646 melanomas of the series. The prognostic parameters were compared with the melanomas of the series at the same stage. RESULTS: The melanomas with unknown primary site represented 2.94 p. 100 of our series and concerned 10 men and 9 women with a median age of 60 years. Eight patients presented stage III melanomas, according to MD Anderson's classification and 11 stage IV. Relapse after surgery was observed in 63 p. 100 of patients and 9 deceased during the observation period. In stage III patients the probability of survival after 2 years was of 51 p. 100 and for stage IV 34 p. 100. DISCUSSION: In our series the frequency of melanomas of unknown primary site is comparable to that observed in other studies. Compared to melanomas of known primary site, there was a preponderance in men and in slightly older patients. There was a majority of single glandular localizations and no particular site was preponderant. Survival of Stage III patients was comparable to that of melanomas of know primary site. However, for stage IV patients it appeared better, as has been noted in other series. Treatment of metastatic melanomas of unknown primary site should therefore be the same as that of classical forms. Whenever possible, surgery remains the first indication. Search for the primary site must be orientated by clinical examination including complete examination of the skin and mucosa (ENT, ophthalmologic and genito-urinary), eventually associated with paraclinical investigations, depending on the symptoms.
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