Acral vasculitis induced by Immune Checkpoint Inhibitor : case series and literature review

Valérian Rivet^1,2*Benoit Guillon²Vincent Sibaud²Jérémie Dion^1,2Andréa Pastissier^1,2Karen Delavigne^1,2Pierre Cougoul^1,2Odile Rauzy^1,2Thibault Comont^1,2

• ¹Centre Hospitalier Universitaire de Toulouse, Toulouse, Occitanie, France
• ²Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France

Introduction. Immune Checkpoint Inhibitors (ICIs) may cause various immunerelated Adverse Events (irAEs). Among them, vascular involvement is still considered as uncommon irAEs and concern mostly large/medium vessels. Acral small-vessel vasculitis has been described and can lead to severe digital necrosis. Case presentation. Herein, we present 3 cases after pembrolizumab, nivolumab and combination nivolumab/ipilimumab for lung adenocarcinoma, renal cell carcinoma and melanoma. Two patients had Raynaud'like syndrome. All of them presented digital ischemia of both hands with severe acral necrosis in first case. Management consisted in ICI discontinuation, high doses steroids and vasodilator agents with good evolution in the 3 cases. No rechallenge of ICI has been attempted. Discussion. We found 12 others cases in literature review to build a cohort of 15 patients, mostly male with median age of 60-years-old. Lung cancer and melanoma are the most common tumor. The mostly frequently used ICIs was pembrolizumab. The median time to onset was 8 weeks. The main clinical presentation is a distal and painful necrosis mostly on hands with bilateral involvement. Toes were affected in only 2 cases. All cases were severe features with grade  3. Eleven patients were treated by steroids and vasodilator agents. ICI was discontinued permanently in all patients. Conclusion. ICI-induced small-vessels vasculitis can lead to severe digital ischemia, often in male and preceded by Raynaud'like syndrome with mostly bilateral and hands involvement. Data are still missing to optimize management of this patients.