Abstract

Abstract Skin toxicities are the most common immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment, an emerging field in dermatology. A wide spectrum of skin irAEs, including lichenoid reactions, vitiligo, bullous pemphigoid and other autoimmune skin diseases, have been reported. Psoriasiform irAEs may occur as an exacerbation of pre-existing disease or de novo and often occur later than other skin irAEs. Most cases reported to date are of chronic plaque and palmoplantar psoriasis. Generalized pustular psoriasis has been reported in fewer than 10 cases. We present a patient with mild pre-existing psoriasis who developed plaque psoriasis, evolving into severe pustular psoriasis after 4 months of pembrolizumab therapy for lung cancer. A 67-year-old man with stage 4 lung adenocarcinoma developed a widespread, itchy psoriasiform rash 3 months after starting pembrolizumab. He had a history of rheumatoid arthritis (RA) and pembrolizumab was started when he had progressed through chemotherapy. The RA was controlled on prednisolone, which was increased when methotrexate was discontinued shortly after diagnosis of lung cancer. He had a family history of psoriasis, and although he had previously been noted to have limited plaque and nail psoriasis, this had required minimal treatment. Within 2 months of starting pembrolizumab, he developed scaly, red plaques affecting more than 30% body surface area (BSA). The oncology team diagnosed a grade 3 skin toxicity and increased doses of oral steroids. Upon steroid tapering, the rash flared and was diagnosed in dermatology as consistent with exacerbation of pre-existing plaque psoriasis secondary to pembrolizumab and high-dose steroids. He partially responded to skin-directed treatment, but 2 months later following his sixth cycle of pembrolizumab, he progressed to generalized suberythrodermic pustular psoriasis. He was treated with acitretin and methotrexate. The incidence of ICI-mediated psoriasis and psoriasiform irAEs is approximately 4% of all skin toxicities. A cohort study by the European Network for Cutaneous Adverse Event to Oncologic Drugs group reported that 70% of 115 patients had no history of psoriasis. Ten per cent of psoriasiform irAEs were categorized as severe, involving more than 30% BSA. However, only eight (7%) had pustular involvement and 2% erythroderma. Treatment options include acitretin, methotrexate, apremilast and biologics. Guttate psoriasis and grade 2/3 disease were significant positive predictors for the antitumour response of ICIs. In summary, ICI-related psoriasis is an increasingly common problem with widespread use of immunotherapy. Early diagnosis and adequate management with agents that do not interfere with immunotherapy, or with the underlying malignancy, and close liaison with oncology are crucial.

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