Citation: British Journal of Dermatology. 2019, 181, 136
Author: Yip V.; Olsson-Brown A.; Pirmohamed M.; Hindle E.
Abstract: Immune checkpoint inhibitors (ICIs) are immunomodulatory agents used in the treatment of an increasing number of malignancies. They inhibit tumour-induced immunosuppression and reactivate tumour-specific cytotoxic T lymphocytes resulting in control of malignant disease (Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12: 25264). However, off-target tissue effects can lead to immune-related adverse effects (irAEs), most commonly in the skin (Sibaud V. Dermatologic reactions to immune checkpoint inhibitors: skin toxicities and immunotherapy. Am J Clin Dermatol 2018; 19: 34561). From May 2014 to July 2018, all cases of immunotherapy-induced cutaneous irAEs referred to a specialist dermatology unit were reviewed. Demographics, clinical features, investigations and outcomes for patients were recorded. Sixteen patients were referred with ICI-induced cutaneous toxicity. Nine (56%) were female and seven (44%) male. Their mean age was 67.8 years (range 4881). The mean time to reaction was 3.6 months after starting ICI treatment (range 18). Melanoma (n = 11) was the most common indication for ICI therapy, followed by nonsmall-cell lung cancer (n = 5). Eleven patients experienced irAEs secondary to pembrolizumab, three to combination ipilimumab/nivolumab therapy and one to ipilimumab and nivolumab, respectively. The most common cutaneous irAEs were eczema (n = 9) and lichenoid reactions (n = 3). Individual cases of psoriasis, inflammatory rash, petechiae and telogen effluvium were reported. No cases of severe cutaneous adverse reactions (e.g. tevensJohnson syndrome) were reported. Treatment with oral (n = 9) or topical (n = 4) corticosteroids was most often prescribed. Intravenous corticosteroids, combination topical corticosteroidantiinfective, acitretin and methotrexate were prescribed to individual patients. Eight patients required a protracted course of treatment. Cutaneous toxicities resulted in discontinuation of ICI therapy in one patient
and delayed treatment in two cases, and led to modification of combination therapy in one case. Cutaneous irAEs most commonly manifested as an itchy erythematous rash clinically consistent with eczema. Corticosteroids were required in the majority of cases. In some cases, cutaneous irAEs resulted in delay or discontinuation of ICI therapy. As ICI usage expands, cutaneous adverse events will become an increasing issue, requiring further research to elucidate pathogenic mechanisms in order to improve clinical management.
