Abstract
e20041 Background: Vemurafenib, a selective BRAF inhibitor, has recently demonstrated improved overall survival in metastatic melanoma. Frequent cutaneous side effects have been reported with vemurafenib, mostly non severe. We report the first case of bullous DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) related to vemurafenib. Methods: Case report: A 69 year old man presented with a BRAF mutated multimetasatic melanoma. Vemurafenib, 960 mg orally twice daily, was started in August 2012. Treatment was discontinued 1 month later because of a grade 2 rash and nausea. Treatment was re-introduced 10 days later with reduction of the dose, 480 mg twice daily. Four days later, the patient had fever, diffuse rash with pustular blistering and eosinophilia up to 1000/mm3. Despite withdrawal of vemurafenib, skin detachment appeared with extension on more than 90% of the body surface and erosions involving oral and genital mucosa requiring admission in intensive care burn unit. A skin biopsy revealed infiltration of the epidermis and the upper dermis with lymphocytic lichenoid vasculitis and focal necrolytic keratinocytes. Intravenous steroids were provided and lesions rapidly resolved with total epithelisation within 15 days. To date, the patient is still alive and undergoes active palliative care. Results: Discussion: DRESS syndrome is a severe drug reaction defined as an acute and severe heterogeneous rash with general symptoms, biological abnormalities, and visceral damages. It occurs from 3 to 6 weeks after drug administration. With a Kardaun score of 4, there were several arguments for a DRESS syndrome to vemurafenib: diffuse and acute rash occurring after 5 weeks of treatment, initial eosinophilia, aggravation of skin lesions despite withdrawal of the culprit drug, histological features and rapid improvement after steroid treatment. With more than 90% of body surface skin detachment, requiring treatment in burn center, the diagnosis was a very severe bullous DRESS syndrome. Vemurafenib was the only culprit drug in our case, as the patient did not received any other drug. Conclusions: Though toxic epidermal necrolysis has been reported yet with vemurafenib, no case of DRESS syndrome has been described to date.
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