Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations.

BACKGROUND: Genetic mutations in the plectin gene (PLEC) cause autosomal recessive forms of epidermolysis bullosa simplex (EBS) associated with either muscular dystrophy (EBS-MD) or pyloric atresia (EBS-PA). Phenotype-genotype analysis has suggested that EBS-MD is due mostly to genetic mutations affecting the central rod domain of plectin, and EBS-PA to mutations outside this domain. OBJECTIVES: This study aimed to describe new phenotypes of patients with EBS-MD and EBS-PA, to identify novel PLEC mutations and to establish genotype-phenotype correlations. METHODS: Seven patients with a suspicion of EBS linked to PLEC mutations were included. A standardized clinical questionnaire was sent to the physicians in charge of each patient. Immunofluorescence studies of skin biopsies followed by molecular analysis of PLEC were performed in all patients. RESULTS: We report the first case of nonlethal EBS-PA improving with age, the first multisystemic involvement in a patient with lethal EBS-PA, and the first patients with EBS-MD with involvement of either the bladder or oesophagus. Eleven novel PLEC mutations are also reported. CONCLUSIONS: Our results confirm that EBS-PA is linked to mutations in the distal exons 1-30 and 32 of PLEC. Long-term survival is possible, with skin improvement, but a delayed onset of MD is probable. While EBS-MD is linked to PLEC mutations in all exons, in most cases one of the mutations affects exon 31. The precocity of MD seems to be linked to the type and localization of the PLEC mutation(s), but no correlation with mucosal involvement has been found.

[Eruptive naevi in epidermolysis bullosa hereditaria patients]. / Nævus éruptifs sur épidermolyse bulleuse héréditaire.

BACKGROUND: EB naevus (EBN) are little-known, atypical, eruptive, pigmented melanocytic lesions that may occur in former sites of bullae occurring in epidermolysis bullosa hereditaria (EBH). We sought to describe the characteristics of such lesions and assess their course. PATIENTS AND METHODS: This was a retrospective, two-centre study in which data was collated from the medical files of patients with EBN. We analyzed the patients' demographical data as well as the clinical, dermatoscopic, pathological features of EBN and their progression. RESULTS: Eight patients were studied: they were principally Caucasian (5/8), with a sex ratio of 1. All variants of EBH were represented and most were recessive (63%). We analysed 22 EBN, all atypical and emerging before the age of 10 years (73%), ubiquitously distributed and measuring greater than 5 cm(2) (25%). Of the 13 EBN subjected to dermatoscopy, 12 exhibited a benign reticular pattern. Four were biopsied, and analysis revealed three common naevi and one lentigo. After a median follow-up of 8 years, the EBN seen were either stable (68%), had regressed (23%) or had disappeared (one case). No cases of melanoma were diagnosed. DISCUSSION: EBN are acquired and atypical pigmented naevi. Sixty-four cases of EBN have been reported in the literature up to date. The dermatoscopic features may be evocative of melanoma (17/23 EBN), but to our knowledge no cases of melanoma at a naevus site have been reported. Recessive transmission of EBH appears to be a risk factor (63% of cases), a finding supported by certain pathophysiological hypotheses. CONCLUSION: EBN present atypical clinical and dermatoscopic features. However, while prophylactic total excision did not appear warranted in the absence of any reported cases of melanoma, regular clinical follow-up is recommended.

[Strontium ranelate-induced DRESS syndrome]. / Syndrome d'hypersensibilité médicamenteuse (DRESS) au ranélate de strontium.

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe form of adverse drug reaction. Strontium ranelate has recently been authorised for postmenopausal osteoporosis. We report a case of strontium ranelate-induced DRESS complicated by linear Ig A dermatosis due to vancomycin. CASE REPORT: A 77-year-old woman with osteoporosis had been treated by strontium ranelate for 4 weeks when she developed a febrile generalized skin rash. Blood tests showed eosinophilia (12.74 × 10(9)/L) and liver damage. A diagnosis of DRESS was made, leading to discontinuation of strontium ranelate and prescription of systemic corticosteroids. Two days later, methicillin-resistant Staphylococcus aureus bacteraemia occurred and treatment with vancomycin was started. The liver dysfunction resolved. After two weeks of antibiotherapy, bullous lesions were noted on the thighs. Skin biopsy results suggested a diagnosis of linear IgA bullous dermatosis. Vancomycin was stopped. Two weeks later, the eruption resolved. The eosinophil count gradually returned to normal after four months of corticosteroid therapy. DISCUSSION: More than 15 cases of DRESS syndrome have been reported in Europe, including 2 deaths related to ranelate strontium, prompting European health authorities to publish a warning concerning the risk of strontium ranelate-induced DRESS. A particular feature of our patient was complication with linear IgA bullous dermatosis caused by vancomycin. In conclusion, it is essential to be aware of the risk of severe cutaneous reaction to strontium ranelate, a new drug used to treat osteoporosis.

[Cutaneous lupus induced by etanercept in rheumatoid arthritis]. / Lupus érythémateux cutané induit par étanercept au cours de la polyarthrite rhumatoïde.

Therapy with anti-TNFalpha in rheumatoid arthritis may induce autoimmune disorders. Induction of autoantibodies is frequently observed, but lupus-like syndrome is rare and few cases only have been reported. We report a 41-year-old female, treated with etanercept for a rheumatoid arthritis, who developed a cutaneous lupus induced without any other organ involvement, associated with high ANA and DNA antibody titres. The skin biopsy and the histological analysis with immunofluorescence confirmed the diagnosis. The anti-TNFalpha treatment was stopped. Corticosteroids were increased and hydroxychloroquine administered because skin lesions persist after three months.

[Protein S100 beta and Melanoma Inhibitory Activity (MIA): a prospective study of their clinical value for the early detection of metastasis in malignant melanoma]. / Protéine S100 Béta et Melanoma Inhibitory Activity (MIA) sériques: étude prospective de leur valeur pour la détection précoce de métastases dans le mélanome.

BACKGROUND: We examined whether serum values for proteins S100B and MIA could allow early and reliable screening of metastatic growth in melanoma. PATIENTS AND METHODS: We carried out a prospective study from 1998 to 2005 in patients presenting non-metastatic melanomas with a Breslow score>0.75 mm. Four PS00B and MIA measurements per patient were performed at regular intervals over 1 to 2 years. Blood samples were analysed for PS100B and MIA using an ELISA technique. RESULTS: Fifty patients were analysed. The maximum interval between collection of samples was 8 months. Metastatic development was noted in 15 patients. Where melanoma progressed to stage III, sensitivity was 33% for PS100B and 25% for MIA. Where it progressed to stage IV, sensitivity was 50% for PS100B and 30% for MIA. A rise in these values preceded discovery of metastasis in 3 cases for PS100B and of MIA in 1 case. Specificity of the assays was 100% for PS100B and 91% for MIA. DISCUSSION: Sensitivity and specificity were better for PS100B than for MIA regarding detection of metastasis during follow-up of thick melanomas. The ELISA technique used in our study seemed to increase the specificity of the assay but not its sensitivity compared to other techniques used previously. We may thus confirm the benefits of PS100B assay for early detection of metastasis in melanomas. However, this laboratory surveillance method is not an acceptable substitute for regular clinical follow-up due to its low sensitivity.

Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients.

BACKGROUND: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital disorder characterized by the association of skin lesions, hearing loss and vascularizing keratitis. KID syndrome is caused by autosomal dominant mutations in the connexin 26 gene (GJB2). OBJECTIVES: To establish whether there is a correlation between genotype and phenotype in KID syndrome. METHODS: Clinical examination and molecular analysis of GJB2 were performed in a cohort of 14 patients with KID syndrome originating from 11 families. We also reviewed the 23 cases with molecular analysis previously reported in the literature. RESULTS: The patients displayed the classical signs of KID syndrome with the additional finding of inflammatory nodules in six patients (43%); this clinical finding has not been described previously in the literature. One patient presented at the age of 18 years with a fatal carcinoma of the tongue, an extremely rare reported complication. For seven of the 11 families (64%) the disease was sporadic, whereas it was familial in the remaining four families (36%). Twelve patients (86%) were heterozygous for the p.Asp50Asn mutation and two patients (14%) were heterozygous for the p.Ser17Phe mutation. Surprisingly, a family in which we personally examined the healthy parents had two affected children heterozygous for the p.Asp50Asn mutation, suggesting germinal mosaicism. Compared with patients with the p.Asp50Asn mutation, the two patients with the p.Ser17Phe mutation had more severe skin involvement. One of these two patients experienced a carcinoma of the tongue. CONCLUSIONS: Familial cases appear to be more frequent than reported in the literature. The possibility of germinal mosaicism must be taken into account for genetic counselling. This study also suggests that patients with the p.Ser17Phe mutation may have a more severe phenotype and could be at higher risk for tongue carcinoma.