Nivolumab-induced lichenoid dermatitis occurring in a patient with metastatic melanoma successfully treated with alitretinoin

Anti‐programmed cell death 1 (anti‐PD1) monoclonal antibodies give durable disease control in several malignancies, including melanoma. Most of their cutaneous adverse effects (AEs) are mild.1 However, we report a patient who developed a severe lichenoid dermatitis involving the hands and feet while on nivolumab immunotherapy. A 70‐year‐old man with metastatic B‐RAF mutant melanoma of the bladder was commenced on nivolumab in December 2013. Within a few months, his fingernails became brittle and painful. One year later, he developed sudden‐onset dystrophy and onycholysis of his fingernails and toenails, and painful hyperkeratosis and fissuring of his feet and hands (Fig. 1a–d). (a, b) Dystrophy and onycholysis of (a) fingernails and (b) toenails; (c) hyperkeratosis and fissuring of palms; and (d) painful hyperkeratosis and fissuring of feet. Skin biopsy showed significant hyperkeratosis, psoriasiform hyperplasia, a brisk upper dermal lymphocytic infiltrate with a few eosinophils, and frequent epidermal apoptoses consistent with a lichenoid drug eruption (Fig. 2). Skin biopsy from the patient's hand showed significant hyperkeratosis, psoriasiform hyperplasia, a brisk upper dermal lymphocytic infiltrate with a few eosinophils and frequent epidermal apoptosis, consistent with a lichenoid drug eruption (haematoxylin and eosin, original magnification × 4). The patient was given treatment with maximal topical therapy without much benefit. Significant improvement occurred after a break in nivolumab but worsened again on treatment recommencement, confirming a causal relationship. The patient was subsequently started on a weaning regimen of high‐dose prednisolone and acitretin, but acitretin was later stopped because of nausea and lack of clinical benefit. Nivolumab was stopped and the patient received intravenous methylprednisolone for 3 days, which resulted in significant improvement of both the hands and feet. Patch testing was performed to exclude any other possible trigger and this was negative. The patient was continued on systemic steroids but the disease flared again on weaning, and the patient was then commenced on alitretinoin 30 mg once daily before successful taper to 10 mg once daily. His skin remained stable over a follow‐up of 6 months and his melanoma remains in remission. Nivolumab is an anti‐PD1 monoclonal antibody that works by targeting the immune checkpoint pathway PD‐1. PD1 is expressed on the surface of activated T cells. Its ligand, programmed death ligand 1 (PD‐L1) is expressed by many cancers and binds to PD1, inactivating T cells. Nivolumab acts by blocking PD‐1, inhibiting binding to PD‐L1, thus allowing T cells to attack cancer cells. Usually its cutaneous AEs are mild,1 but lichenoid mucocutaneous eruptions and cases of bullous pemphigoid have been reported.2 3 Erythematous papules with scale are the most commonly reported clinical morphology of lichenoid eruptions. However, palmoplantar lesions, similar to our patient, have also been described.4 Most cases responded to treatment with topical corticosteroids alone, while phototherapy was used to treat some patients with palmoplantar lesions, with only one patient requiring cessation of anti‐PD1 therapy. The pathogenesis of these reactions is unknown, butit has been proposed that nivolumab, by blocking PD‐1 on T cells that normally act to maintain immune tolerance to self‐antigens, may ‘unmask’ an immune response to a pre‐existing antigen located at a specific body site.5 To our knowledge, this is the first reported case of successful treatment with alitretinoin in a patient with a severe palmoplantar lichenoid eruption secondary to nivolumab. This case highlights the importance of early recognition of the immunotherapy‐associated lichenoid eruptions, which can cause significant morbidity for patients on potentially lifesaving medication, and offers another potential treatment option for these patients. Conflict of interest: the authors declare that they have no conflicts of interest.