P046 Dermatopathology in the diagnosis of chemotherapy- and immunotherapy-induced vasculitis presenting with extensive digital necrosis: a clinicopathological case

Abstract

Chemotherapy-induced vasculitis is an uncommon and challenging adverse reaction to diagnose, with severe digital necrosis being an exceptional presentation. Its pathophysiology involves direct endothelial damage, immune-complex-mediated immunological activation and paraneoplastic phenomena. We present the case of a 54-year-old man diagnosed with stage IV cholangiocarcinoma, undergoing treatment with durvalumab, gemcitabine and cisplatin since November 2024. Three days after the infusion of the sixth cycle, he developed violaceous lesions on the fingertips of both hands, which rapidly progressed to dry distal necrosis affecting five fingers of the hands and four toes. This was accompanied by severe pain, without fever or other systemic manifestations. Initial immunological studies were negative, namely antinuclear antibodies, antineutrophil cytoplasmic antibodies, cryoglobulins, C3, C4, anticardiolipins and β2-glycoprotein. Subsequently, an arterial Doppler study revealed no vascular occlusions, ruling out an ischaemic cause of embolic or thrombotic origin. Given the persistence of the lesions and clinical progression, dermatology was consulted and a skin biopsy of the left hand was performed. Histopathology showed transmural coagulative necrosis with a mixed perivascular inflammatory infiltrate and possible fibrinoid necrosis, consistent with vasculitis. Immunofluorescence was negative; however, interpretation was limited due to the extensive necrosis present. In the absence of infection, thrombotic phenomena or demonstrable autoimmunity, and considering the temporal and pathological context, the findings were consistent with a diagnosis of rapidly progressive distal digital necrosis secondary to chemotherapy- or immunotherapy-induced toxicity with a possible paraneoplastic component. The lesions stabilized without requiring amputation. This case highlights the importance of considering severe vascular toxicity as a potential adverse effect of combined chemotherapy and immunotherapy, emphasizing the need for timely skin biopsies and accurate clinicopathological and dermatological correlation. It also underscores the value of close monitoring to prevent major complications.