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Allergy to beta-lactam antibiotics is a common condition and about 10% of patients report being allergic to penicillin. However, this diagnosis is largely overestimated. Two types of allergy should be distinguished and include immediate hypersensitivity that can lead to anaphylactic shock and delayed hypersensitivity, ranging from the most common maculopapular exanthema to severe bullous toxidermia or life-threatening DRESS. Allergy challenge with oriented skin tests according to the clinical features, supplemented with oral challenge in the absence of contraindication, will confirm or invalidate the diagnosis of beta-lactam allergy and will help to identify if necessary safe alternatives to beta-lactams.

Resume Le virus Zika (ZIKV), initialement identifie en 1947, est un Flavivirus re-emergent, principalement transmis par les piqures de moustiques du genre Aedes . Jusqu’aux recentes epidemies dans les iles du Pacifique et en Amerique centrale et du sud, il etait repute a l’origine d’une maladie benigne, asymptomatique dans la majorite des cas, ou avec des symptomes moderes non specifiques (fievre, eruption, conjonctivite, arthralgies…). Au cours de l’epidemie actuelle, d’une ampleur inedite, de nouveaux modes de transmission (transfusionnel, perinatal, sexuel) et des complications neurologiques severes telles que des malformations congenitales chez les fœtus de meres infectees et des syndromes de Guillain-Barre chez l’adulte ont ete mis en evidence. Cette situation, dans un contexte de potentielle pandemie mondiale a venir, a amene l’Organisation mondiale de la sante (OMS) a declarer l’infection a ZIKV urgence de sante publique de portee internationale en fevrier 2016.

DRESS syndrome (drug rash with eosinophilia and systemic symptoms) or drug hypersensitivity syndrome, presents a prevalence of 2% to 3% among the in-hospital population. In the present case, patients admitted to the intensive care unit (ICU) after intracranial surgery presented generalized facial edema, maculopapular exanthema and scaly erythroderma. During intra-buccal inspection, multiple ulcerated lesions with bleeding were observed at the lowest stimulation on the lips and oral mucosa at various localization sites. Laboratory tests revealed eosinophilia, thrombocytopenia, leukocytosis, and elevation of TGO, TGP, and CPK levels. In view of the clinical picture, it was found to be DRESS syndrome. The treatment of oral lesions consisted of cleaning, crust removal, and low-intensity laser therapy with red light. After 10 sessions of laser therapy, ulcerated lesions were resolved. The patient was discharged and has been under follow-up for 7 months.

Resume Introduction Nous rapportons le premier cas de necrolyse epidermique toxique (NET) survenue sous vemurafenib. Observation Une femme de 75 ans etait traitee par vemurafenib pour un melanome de stade IV porteur de la mutation BRAF V600E. Elle presentait brutalement de la fievre, un erytheme maculo-papuleux diffus prurigineux, un �deme palpebral, une bulle palmaire, une conjonctivite, une cheilite et des erosions muqueuses. L'evolution se faisait vers un decollement touchant 50 % de la surface cutanee. La biopsie cutanee montrait une dermatose lichenoide, focalement vesiculeuse avec de nombreux polynucleaires eosinophiles. L'etude en immunofluorescence directe (IFD) etait negative. Le vemurafenib etait le seul medicament imputable. Nous concluions a une NET au vemurafenib. Discussion Il s'agit a notre connaissance du premier cas rapporte de NET au vemurafenib mais cet effet indesirable, quoique deja decrit dans l'etude BRIM-3, semble rare en pratique clinique. Dans la litterature, d'autres reactions cutanees severes ont ete decrites. Parmi elles, un cas de syndrome de Stevens-Johnson chez une patiente sous vemurafenib, precedemment traitee par ipilimumab. De maniere plus frequente, les reactions cutanees a type d'efflorescence de lesions hyperkeratosiques benignes parfois accompagnees d'authentiques carcinomes epidermoides ou keratoacanthomes sont rapportees et justifient une surveillance cutanee reguliere des patients traites par vemurafenib. Conclusion Devant l'apparition d'un exantheme maculo-papuleux sous vemurafenib, la poursuite du traitement doit etre reevaluee puisque le risque d'evolution plus grave, comme ici, une NET, n'est pas nul. ________________________________________ Summary Background Herein we report the first case of toxic epidermal necrolysis (TEN) occurring with use of vemurafenib. Patients and methods A 75-year-old female patient was being treated with vemurafenib for stage IV melanoma with BRAF V600E mutation. She suddenly presented fever, diffuse pruriginous maculopapular erythema, palpebral edema, palmar bulla, conjunctivitis, cheilitis and mucosal ulceration. The condition progressed towards detachment affecting 50% of the skin area. Cutaneous biopsy revealed lichenoid dermatosis, chiefly vesicular with numerous eosinophils. Direct immunofluorescence (IFD) was negative. Vemurafenib was the only drug to which the reaction was ascribable and we concluded on vemurafenib-induced TEN. Discussion To our knowledge, this is the first reported case of vemurafenib-induced TEN, but this adverse effect, although already described in the BRIM-3 study, appears rare in clinical practice. Other severe skin reactions have been described in the literature. These include a case of Stevens-Johnson syndrome in a female patient treated with vemurafenib and previously receiving ipilimumab. A more common occurrence is cutaneous reactions involving efflorescence of benign hyperkeratotic lesions, occasionally accompanied by authentic epidermal carcinoma or keratoacanthoma, and requiring regular dermatological monitoring of patients treated with vemurafenib. Conclusion If maculopapular exanthema occurs under vemurafenib, continuation of this treatment should be reassessed since the risk of progression to a more serious condition such as TEN, as seen in the present case, cannot be ruled out. Mots cles " Vemurafenib; " Necrolyse epidermique toxique; " Syndrome de Lyell; " Melanome Keywords " Vemurafenib; " Toxic epidermal necrolysis; " Lyell's syndrome; " Melanoma