The Cutaneous Side Effects of Selective BRAF Inhibitors and Anti-CTLA4 Agents: the Growing Role of the Dermatologist in
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MEDICAL SURGERY (CJ MILLER, SECTION EDITOR)
The Cutaneous Side Effects of Selective BRAF Inhibitors and Anti-CTLA4 Agents: the Growing Role of the Dermatologist in the Management of Patients with Metastatic Melanoma Lisa Pappas-Taffer & Misha Rosenbach & Emily Y. Chu
Published online: 5 April 2013 # Springer Science+Business Media New York 2013
Abstract Two new drugs—vemurafenib, a selective BRAF inhibitor (BRAFi), and ipilimumab, an anti-CTLA4 monoclonal antibody—were approved by the FDA in 2011 and have demonstrated a survival benefit in the treatment of metastatic melanoma. Cutaneous side effects are common with both medication classes, occurring in up to 92 % of patients treated with BRAFis, and up to 69 % of patients treated with antiCTLA4 therapy. Cutaneous eruptions associated with BRAFis include benign and malignant squamous and melanocytic proliferations, photosensitivity, morbilliform eruptions, diffuse keratosis pilaris, Grover’s disease, seborrheic dermatitis, panniculitis, hand-foot skin reaction, epidermal cysts, and hair changes. Dermatologic findings associated with anti-CTLA4 agents include morbilliform eruptions, hair depigmentation, vitiligo, and alopecia areata. Given the array of skin eruptions occurring in melanoma patients receiving these agents, the role of the dermatologist in monitoring and treating these patients is paramount.
Panniculitis . Hand-foot skin reaction . Palmar-plantar hyperkeratosis . Cysts . Alopecia . Curly hair . Nevi . Basal cell carcinoma . Ipilimumab . Hair depigmentation . Vitiligo
Keywords Melanoma . BRAF inhibitors . Vemurafenib . Dabrafenib . Anti-CTLA4 . Ipilimumab . Squamous cell carcinoma . Keratoacanthoma . Verrucous keratoses . Photosensitivity . Keratosis pilaris . Grover’s disease . Acantholytic dyskeratosis . Seborrheic dermatitis .
Selective V600E-BRAF Inhibitors
Lisa Pappas-Taffer wrote the manuscript. Misha Rosenbach and Emily Chu edited and provided photographs for the manuscript. L. Pappas-Taffer (*) : M. Rosenbach : E. Y. Chu Department of Dermatology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA e-mail: [email protected]
Introduction BRAFi-associated eruptions can be attributed to either the inhibition or paradoxical activation of the RAS/RAF/ MEK/ERK signaling cascade, which regulates cellular proliferation and differentiation [1]. In contrast, anti-CTLA4associated eruptions are largely attributed to the inhibition of regulatory immune mechanisms resulting in enhanced T cell response against self-antigens [2]. We review the literature describing these diverse cutaneous reactions, characterizing their clinical and histologic appearance, frequency of occurrence, timing of onset, and treatment options.
Introduction BRAF is a serine/threonine kinase component of the RAS/RAF/MEK/ERK signaling cascade, also known as the mitogen-activating protein kinase (MAPK) pathway, involved in cellular proliferation and differentiation. At least 50 % of all melanomas harbor an activating BRAF gene mutation, with a
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