Generalized morphoea in the setting of combined immune checkpoint inhibitor therapy for metastatic melanoma: A case report

RATIONALE: Immune checkpoint inhibition has dramatically altered the therapeutic landscape in the treatment of a range of locally advanced and metastatic skin cancers. In particular, the treatment of metastatic melanoma with combined anti-programmed cell death protein 1 (anti-PD1) and anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) antagonists has resulted in median 5-year survival rates of over 50%. However, combined immune checkpoint inhibitor therapy frequently results in the development of immune-related adverse events (irAE) which can be severe and life-threatening. While the typical irAEs, namely colitis, thyroiditis, and hepatitis are well recognized, cutaneous irAEs are varied and can be difficult to accurately diagnose. PATIENT CONCERNS: A 61-year-old female with metastatic melanoma presented with widespread indurated, waxy skin changes, and weight loss following combined anti-PD1 and anti-CTLA4 immunotherapy. DIAGNOSES: Generalized morphea in the setting of combined immunotherapy. INTERVENTIONS: Dexamethasone pulse therapy (100 mg i.v. over 3 days) was combined with topical therapy (clobetasone propionate ointment) and physiotherapy. Four cycles of dexamethasone pulse therapy, at 4 weekly intervals, led to an improvement in the skin changes, accompanied by increased mobility. However, the changes did not resolve completely. OUTCOME: Staging examinations revealed progressive melanoma brain metastases and despite 2 further cycles of combined anti-PD1 and anti-CTLA4 immunotherapy followed by 1.5 cycles of Fotemustine, the patient died 22 months after the development of the scleroderma-like skin changes. LESSONS: Cutaneous irAEs are varied in nature and severity. Sclerotic skin changes are rare, but unlike cutaneous irAEs related to immune checkpoint inhibitor therapy, they are often refractory to standard treatment with systemic corticosteroids. Clinicians should be aware of immunotherapy-related scleroderma to prompt dermatological evaluation to facilitate early recognition and initiate treatment. Administration of systemic immunosuppression should be carefully balanced against the risk of promoting melanoma progression.