BI33 Localized granulomatous reaction on the hand secondary to combination dabrafenib and trametinib therapy for metastatic melanoma

Abstract

Targeted therapies, including inhibitors of BRAF and mitogen-­activated protein kinase kinase (MEK), have significantly improved outcomes for patients with BRAF-mutant metastatic melanoma. Although generally well tolerated, these agents are associated with a range of immune-mediated adverse effects, including rare granulomatous reactions that may mimic disease progression. We describe a 64-year-old man with BRAF V600-mutant metastatic melanoma who developed a localized, mildly pruritic papular eruption confined to the dorsum of the right hand 3 months after commencing combination dabrafenib–trametinib therapy. Histopathological examination demonstrated noncaseating granulomatous inflammation with scattered eosinophils. Extensive microbiological investigations were negative, supporting a drug-related granulomatous reaction. No specific treatment was required, and the eruption resolved spontaneously over 6 months while targeted therapy was continued uninterrupted. Granulomatous reactions associated with BRAF and MEK inhibitors have previously been described at sites such as tattoos, surgical scars and lymph nodes, and as more disseminated sarcoid-like reactions. To our knowledge, this represents the first reported case of a granulomatous reaction localized to the hand linked with BRAF and MEK inhibitor therapy. The underlying mechanism is thought to involve immune modulation mediated by mitogen-­activated protein kinase pathway inhibition, promoting a T helper 1-dominant response and macrophage activation. Recognition of this presentation is clinically important, as granulomatous inflammation can demonstrate increased uptake on fluorodeoxyglucose positron emission tomography–computed tomography, potentially mimicking melanoma progression. This case highlights a previously unreported cutaneous manifestation of BRAF and MEK inhibitor therapy. Awareness of localized granulomatous reactions at uncommon sites may prevent misdiagnosis, avoid unnecessary investigations and support continuation of effective targeted treatment.