Vemurafenib-Induced Neutrophilic Panniculitis: A New Case and Review of the Literature

Abstract

Vemurafenib has proved to be useful in the treatment of patients with unresectable or metastatic melanoma harboring the BRAF-V600E mutation, with better rates of overall and progression-free survival than previous treatments. Adverse cutaneous effects, such as alopecia, pruritus, photosensitivity reactions, verrucous keratosis, keratoacanthomas, or squamous cell carcinomas, have been described. Thirty cases of vemurafenib-associated panniculitis are available in the literature with variable clinical relevance. Only 9 of them exhibited definitive evidence of neutrophilic panniculitis. They all consist of multiple lesions, usually located in the lower limbs. Histopathologically, they have been described as predominantly neutrophilic, lymphocytic, or mixed, more commonly with lobular location. We report an additional case of neutrophilic panniculitis in a 45-year-old woman treated with vemurafenib for metastatic melanoma, presenting as a single lesion on his right leg. The lesion resolved spontaneously and did not need treatment reduction. The presentation of this condition with a single lesion is particularly challenging. Recognition of this association is important given the increasing use of vemurafenib and the potential implications of treatment withdrawal.

Panniculitis Associated with MEK Inhibitor Therapy: An Uncommon Adverse Effect

“…The clinical presentation of the lesions was similar to other reported cases, with predominance in upper and lower extremities [3, 4, 5, 6, 7, 8, 9, 10]. Like our patient, almost all patients developed arthralgia [3, 4, 5, 6, 7, 8, 9, 10]. Histopathological examination in previous cases outlined lobular, septal, or mixed (both lobular and septal) panniculitis, in one case associated with vasculitis [3].…”

“…It induces an activation of the mitogen-activated protein kinase pathway and cellular proliferation. As reported and summarized by Vasquez-Osorio et al [3], vemurafenib-induced panniculitis seems to affect more women than men (up to 10: 9) [7]. The onset of panniculitis in our patient occurred approximately with the same delay (median of 14.5 days) [3].…”

“…As reported and summarized by Vasquez-Osorio et al [3], vemurafenib-induced panniculitis seems to affect more women than men (up to 10: 9) [7]. The onset of panniculitis in our patient occurred approximately with the same delay (median of 14.5 days) [3]. The clinical presentation of the lesions was similar to other reported cases, with predominance in upper and lower extremities [3, 4, 5, 6, 7, 8, 9, 10].…”

“…The onset of panniculitis in our patient occurred approximately with the same delay (median of 14.5 days) [3]. The clinical presentation of the lesions was similar to other reported cases, with predominance in upper and lower extremities [3, 4, 5, 6, 7, 8, 9, 10]. Like our patient, almost all patients developed arthralgia [3, 4, 5, 6, 7, 8, 9, 10].…”

“…This combination is now the first-line treatment for patients with BRAF V600-mutated metastatic melanoma [1, 2]. Cutaneous adverse effects are significantly reduced with BRAFi and MEKi association including photosensitivity (15% of patients, coBRIM), hand-foot syndrome (6% COMBI-d), hyperkeratosis (6% COMBI-d; 29% coBRIM), alopecia (5% COMBI-d; 30% coBRIM), skin papillomas (1% COMBI-d), keratoacanthomas (8% coBRIM), and squamous-cell carcinomas (11% coBRIM) [1, 2, 3]. While panniculitis has exceptionally been reported with BRAFi, to the best of our knowledge, this rare side effect has never been described with the use of MEKi [4, 5, 6, 7, 8, 9, 10].…”