Development of Two Primary Malignant Melanomas after Treatment with Adalimumab: A Case Report and Review of the Possible Link between Biological Therapy with TNF-α Antagonists and Melanocytic Proliferation

Abstract

Biologics, such as tumor necrosis factor α (TNF-α) antagonists, have revolutionized treatment of several significant inflammatory autoimmune diseases. Nevertheless, issues concerning long-term safety remain to be clarified. There is growing evidence linking biological treatments with the occurrence of malignancies or reactivation of latent ones, including malignant melanoma. We report the case of a 75-year-old male patient who developed 2 primary malignant melanomas (MM) after treatment with adalimumab for rheumatoid arthritis. He was under adalimumab treatment for approximately 12 months before the diagnosis of MM on his right lower leg. After surgical removal and staging, no evidence of metastases was found. A few months later, a second MM developed on the patient’s scalp. The short duration of treatment with adalimumab and the unclear temporal relationship cannot adequately support a probable link between this double MM occurrence and the adalimumab-induced immunosuppressive state. The result of a literature search regarding the possible association between anti-TNF drugs and melanocytic proliferation is provided.

Eruptive Benign Melanocytic Nevi Formation Following Adalimumab Therapy in a Patient with Crohn's Disease

“…Previous cases suggest the tendency of melanocytic nevi to appear on specific locations (palms and soles); however, widespread distribution of nevi involving almost the entire body as in our case is a novel presentation1. Not only benign melanocytic lesions but also malignant melanomas have been reported to develop during or after anti-tumor necrosis factor (TNF)-α therapy235. Thus, a skin examination before and after the use of anti-TNF-α agents could be of value in identifying the development of melanocytic nevi, which often necessitates evaluation to rule out malignant melanoma.…”

The Effects of Biological Agents on Melanocytic Nevi: A Preliminary Report

“…In addition, an increased risk of development of dysplastic nevus (atypical nevus) and development and reactivation of melanoma was also reported during the treatment with biological agents (5,6,9).…”

Segurança do uso de terapias biológicas para o tratamento de artrite reumatoide e espondiloartrites

“…[88][89][90][91] Os mais frequentes são as neoplasias cutâneas não-melanoma, principalmente, o carcinoma basocelular e, com menor frequência, o espinocelular. [89][90][91][92][93][94] Casos de melanoma maligno, entretanto, também já foram descritos em pacientes em uso de terapia anti-TNF. [95][96][97][98][99][100][101][102][103][104] Apesar do papel exato desses fármacos no aparecimento do melanoma não estar bem estabelecido, deve-se prestar muita atenção para o surgimento de lesões pigmentadas ou mudanças das características de nevus preexistentes.…”