BI12 Two skin diseases, one checkpoint inhibitor: cutaneous toxicity from pembrolizumab

Abstract

Pembrolizumab is an anti-programmed death-1 checkpoint inhibitor (CPI) used in a wide range of malignancies. CPI-associated cutaneous immune-related adverse events (irAEs) are common, affecting up to 40% of patients. However, multiple, sequential, mechanistically distinct dermatoses in a single patient are rare. We present a patient with pembrolizumab-associated psoriasis and bullous pemphigoid (BP). A 55-year-old man with locally advanced lung adenocarcinoma and previous chronic plaque psoriasis completed three cycles of neoadjuvant pembrolizumab–pemetrexed–carboplatin. Subsequent surgical resection confirmed complete pathological response and adjuvant pembrolizumab was started. After the first cycle, his psoriasis flared affecting the limbs, scalp, hands and feet. This was successfully controlled with topical therapy. Four months later he developed an intensely pruritic, widespread rash. Pembrolizumab was suspended and prednisolone 40 mg per day started by oncology. On examination, he had inflammatory psoriasiform plaques and erosions on the trunk and legs and a single blister. Skin biopsy demonstrated features of both psoriasis and eosinophilic spongiosis. The biopsy displayed focal subepidermal clefting and basement membrane linear IgG staining, and he had positive pemphigoid antibodies, consistent with coexisting psoriasis and BP. The blistering increased and, after discussion with oncology, doxycycline was initiated and prednisolone weaned. His lung malignancy remains in complete remission and further pembrolizumab has not been required. To our knowledge, sequential psoriasis and BP have not been reported with CPI immunotherapy. Up to 70% of patients with pre-existing psoriasis may have flares, and de novo psoriasis occurs in up to 1–7%, but BP is rare (< 1%). The immunopathogenesis of psoriasis is predominantly driven by T helper (Th)1, Th17 and interleukin-23, whereas BP is Th2 dominated with BP180/BP230 autoantibody formation. This suggests that distinct immune pathways may be unmasked sequentially by immune checkpoint inhibition. Recognition of multiple cutaneous irAEs is important as diagnosis may be delayed, and management strategies may differ significantly. This case underscores the need for vigilance for new, morphologically distinct dermatoses during CPI immunotherapy, even after an initial irAE has been diagnosed and treated.