DRESS syndrome due to vemurafenib treatment: switching BRAF inhibitor to solve a big problem

Abstract

We present a case report of an early-onset drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) induced by vemurafenib (BRAF inhibitor) in a middle-age man affected by a metastatic, BRAF mutant melanoma who was started on first-line metastatic treatment with vemurafenib and cobimetinib.After initiating the treatment, the patient presented an extensive cutaneous rash with eosinophilia and renal impairment. Due the constellation of signs and symptoms, a diagnosis of DRESS syndrome was made which strongly contraindicated the reintroduction of vemurafenib due to its hypersensibility reaction. Thus, vemurafenib was stopped immediately, and we started corticoid treatment with clinical improvement.Due to the contraindication to start vemurafenib again, after multidisciplinary view of the case and having balanced the risks and benefits, we successfully performed a switch to another BRAF inhibitor in a progressively ascending pattern, without any skin toxicity and with a good response of the metastatic melanoma.

Systematic review of BRAF/MEK inhibitors‐induced Severe Cutaneous Adverse Reactions (SCARs)

“…Dabrafenib was reported twice ( n = 2; 3%) as the causative drug of two DRESS cases (one after switching from a vemurafenib‐DRESS‐induced case) 20,21 . All the remainder ( n = 30; 98%) were caused by vemurafenib, which was related with melanoma in all of the cases 12–14,16,20–33 . A total of 64.5% ( n = 20) cases were related to the combination of vemurafenib and cobimetinib; 20,22,27–29 however, when an actual assessment of the culprit drug was performed (Naranjo scale, ALDEN score, patch test and/or in vitro analysis of lymphocyte reactivity), vemurafenib was the solo cause of the SCAR 15,25,27 .…”

“…All the remainder ( n = 30; 98%) were caused by vemurafenib, which was related with melanoma in all of the cases 12–14,16,20–33 . A total of 64.5% ( n = 20) cases were related to the combination of vemurafenib and cobimetinib; 20,22,27–29 however, when an actual assessment of the culprit drug was performed (Naranjo scale, ALDEN score, patch test and/or in vitro analysis of lymphocyte reactivity), vemurafenib was the solo cause of the SCAR 15,25,27 . Interestingly, 45.2% ( n = 14) of the cases received prior immunotherapy, some of them more than one drug (8 cases received nivolumab, 5 pembrolizumab and 4 ipilimumab) 20,22,27–29,32 .…”

Vemurafenib and cobimetinib‐induced toxic epidermal necrolysis in a patient with metastatic melanoma

“…Recent findings confirmed cases of focal necrotizing myopathy with "dropped-head syndrome" (Gauci et al, 2017) To our knowledge, there is only one, recently published case of SJS under combined target therapy (vemurafenib plus cobimetinib) in a patient who had previously received immunotherapy (Lamiaux et al, 2018). Also, DRESS syndrome induced by vemurafenib as part of firstline metastatic treatment of BRAF mutant melanoma with vemurafenib and cobimetinib has been noted (Ros & Muñoz-Couselo, 2018).…”

Desensitization protocol for angio‐oedema induced by encorafenib in a patient with metastatic melanoma

“…Editor Encorafenib is an oral BRAF kinase inhibitor used in patients with BRAFV600-mutated melanoma. 1 Generalized hypersensitivity reactions (HSR) have been described with BRAF inhibitors (BRAFi), 2 but remain rare. Desensitization protocols to overcome HSR by gradual reintroduction of small amounts of the incriminating drug up to full therapeutic doses have been proposed for vemurafenib 3,4 and dabrafenib, 5 but not yet for encorafenib.…”

“…Human b-defensin 2 (HBD-2) is an antimicrobial peptide that was first isolated from psoriatic scales. 2 Apart from antimicrobial activities, HBD-2 is also implicated in immune responses 3 and angiogenesis 4 and has been associated with autoimmune diseases like systemic lupus erythematosus. 5 However, an association between HBD-2 and SSc remains unclear.…”