CASE REPORT BJD British Journal of Dermatology Vemurafenib-induced toxic epidermal necrolysis: possible cross-reactivity with other sulfonamide compounds T. Bell on, 1 V. Lerma, 2 O. Gonz alez-Valle, 3 C. Gonz alez Herrada 3 and F.J. de Abajo 2,4 1 Institute for Health Research, University Hospital La Paz–IdiPAZ, P° Castellana 261, 28046 Madrid, Spain 2 Clinical Pharmacology Unit, Principe de Asturias University Hospital, Madrid, Spain 3 Department of Dermatology, University Hospital of Getafe, Madrid, Spain 4 Department of Biomedical Sciences (Pharmacology), University of Alcal  a, Madrid, Spain Correspondence Teresa Bell  on. E-mail: teresa.bellon@salud.madrid.org Accepted for publication 14 September 2015 Funding sources Research grants from the Instituto de Salud Carlos III-Ministerio de Econom  ıa y Competitividad FIS PI12/02267 (co-founded by FEDER) to F.J.A. and FIS PI13/01768 (co-founded by FEDER) to T.B. Conflicts of interest None declared. DOI 10.1111/bjd.14201 Summary Vemurafenib is a newly licensed target-directed medication. It has been proven to improve the survival of patients with metastatic melanoma and the BRAF V600E mutation; however, adverse cutaneous reactions are frequent. Few cases of life- threatening severe cutaneous adverse reactions (SCARs) induced by vemurafenib have been reported. Dabrafenib, another selective BRAF inhibitor, has been licensed recently as an alternative drug with the same indications. From a molec- ular point of view, both vemurafenib and dabrafenib contain a sulfonamide group; cross-reactivity to sulfonamide compounds has been reported in allergic patients. We report on a patient with vemurafenib-induced toxic epidermal necrolysis (TEN). In vitro analysis of lymphocyte reactivity to vemurafenib showed positive results, confirming drug causality. In addition, lymphocytes from the patient reacted to dabrafenib and to the antibiotic sulfonamide drug sulfamethox- azole. Moreover, lymphocytes from two patients with cutaneous adverse reactions to sulfamethoxazole also reacted to vemurafenib and dabrafenib in vitro. These data strongly suggest that there might be clinical cross-reactivity between BRAF inhibitors and sulfonamides in some patients. Thus, precautions should be taken to avoid sulfonamide drugs as much as possible in patients showing serious hypersensitivity reactions to vemurafenib and vice versa. What’s already known about this topic? • Vemurafenib and dabrafenib are BRAF inhibitors licensed for metastatic melanomas presenting BRAF V600E mutation. • Serious hypersensitivity reactions have been reported for vemurafenib. What does this study add? • Vemurafenib and dabrafenib share a sulfonamide group in their chemical structure. • Lymphocytes from a patient with vemurafenib-induced toxic epidermal necrolysis reacted in vitro to vemurafenib, dabrafenib or sulfamethoxazole. • Clinical cross-reactivity between these drugs is possible in some patients. The selective v-raf murine sarcoma viral oncogene homologue B1 (BRAF) inhibitor vemurafenib was licensed in 2012 for monotherapy of BRAF V600E mutation-positive unresectable or metastatic melanomas. 1 Dabrafenib, another specific BRAF inhibitor, has shown similar results to vemurafenib in a phase III trial. Targeting a BRAF mutation with dabrafenib, in combination with a MEK inhibitor such as trametinib, has become an alternative strategy for overcoming tumour resis- tance to BRAF inhibitors. 2 Adverse skin reactions to vemurafenib are common, although most are mild and manageable with dose reduc- tions. 3 However, severe cutaneous hypersensitivity reactions © 2015 British Association of Dermatologists British Journal of Dermatology (2016) 174, pp621–624 621