R Mössner1, L Zimmer2, C Berking3, C Hoeller4, C Loquai5, E Richtig6, K C Kähler7, J C Hassel8, R Gutzmer9, S Ugurel10. 1. Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany. 2. Department of Dermatology, University of Duisburg-Essen, Essen, Germany. 3. Department of Dermatology and Allergology, University of Munich (LMU), Munich, Germany. 4. Department of Dermatology, Medical University of Vienna, Vienna, Austria. 5. Department of Dermatology, University Medical Center Mainz, Mainz, Germany. 6. Department of Dermatology, Medical University of Graz, Graz, Austria. 7. Department of Dermatology and Venerology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany. 8. Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany. 9. Department of Dermatology and Allergy, Skin Cancer Center, Hannover Medical School, Hannover, Germany. 10. Department of Dermatology, University of Würzburg, Würzburg, Germany.
Abstract
IMPORTANCE: BRAF inhibitors have been licensed for the therapy of BRAF-mutated melanoma. Recently, inflammatory skin lesions clinically resembling erythema nodosum have been reported as therapy side-effects that may lead to treatment discontinuation. OBJECTIVE: To identify and characterize cases with BRAF inhibitor-associated erythema nodosum-like inflammatory skin lesions and development of an algorithm for their management. DESIGN AND SETTING: Retrospective chart review of melanoma patients treated with BRAF inhibitors in 14 departments of Dermatology in Germany and Austria and PubMed search for cases in the literature. RESULTS: Sixteen patients were identified who developed erythema nodosum-like lesions under BRAF inhibitor therapy; 14 had received vemurafenib and two dabrafenib plus trametinib. The most frequently involved body sites were the legs. Histopathology was performed in five cases and revealed panniculitis in three and vasculitis in two patients respectively. Arthralgia and fever were associated symptoms in 44% and 31% of patients respectively. Inflammatory symptoms led to discontinuation of treatment in three patients, while in the majority of cases symptomatic management was sufficient. Skin lesions finally resolved despite continued BRAF inhibitor therapy in seven patients. In the literature, 19 additional patients with similar cutaneous appearance under BRAF inhibitors could be identified. An algorithm for the management of such lesions is proposed. CONCLUSION: Erythema nodosum-like skin lesions histologically correspond to panniculitis and/or vasculitis. Symptomatic treatment may be sufficient. However, additional work-up and interruption of BRAF inhibitor therapy may be necessary in severe cases which are commonly associated with systemic symptoms.
IMPORTANCE: BRAF inhibitors have been licensed for the therapy of BRAF-mutated melanoma. Recently, inflammatory skin lesions clinically resembling erythema nodosum have been reported as therapy side-effects that may lead to treatment discontinuation. OBJECTIVE: To identify and characterize cases with BRAF inhibitor-associated erythema nodosum-like inflammatory skin lesions and development of an algorithm for their management. DESIGN AND SETTING: Retrospective chart review of melanomapatients treated with BRAF inhibitors in 14 departments of Dermatology in Germany and Austria and PubMed search for cases in the literature. RESULTS: Sixteen patients were identified who developed erythema nodosum-like lesions under BRAF inhibitor therapy; 14 had received vemurafenib and two dabrafenib plus trametinib. The most frequently involved body sites were the legs. Histopathology was performed in five cases and revealed panniculitis in three and vasculitis in two patients respectively. Arthralgia and fever were associated symptoms in 44% and 31% of patients respectively. Inflammatory symptoms led to discontinuation of treatment in three patients, while in the majority of cases symptomatic management was sufficient. Skin lesions finally resolved despite continued BRAF inhibitor therapy in seven patients. In the literature, 19 additional patients with similar cutaneous appearance under BRAF inhibitors could be identified. An algorithm for the management of such lesions is proposed. CONCLUSION:Erythema nodosum-like skin lesions histologically correspond to panniculitis and/or vasculitis. Symptomatic treatment may be sufficient. However, additional work-up and interruption of BRAF inhibitor therapy may be necessary in severe cases which are commonly associated with systemic symptoms.
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