P027 Immune checkpoint inhibitor associated vasculitis: a limitation to cancer therapy
Authors: Au Marcus , Faher Anissa , Htut Ei Ei Phyu 
Published: April 2023

Abstract

Background/Aims
The increasing use of immune checkpoint inhibitors (ICIs) underlies the importance of close monitoring and recognition of associated adverse events. We report a rare case of nivolumab-related peripheral vasculitis with digital gangrene and auto-amputation in a patient treated for mesothelioma.

Methods
A 69-year-old male with T4M0N0 pulmonary sarcoid mesothelioma was commenced on second-line Nivolumab therapy. 11 days later, he presented with worsening dyspnoea and dry cough. CTPA demonstrated new bilateral lower zone and peripheral predominant ground glass patchy consolidation consistent with acute pneumonitis. He sustained a significant clinical benefit from IV methylprednisolone and cessation of Nivolumab. 20 days after the pneumonitis episode, the patient re-presented with extremely tender, blue-black discoloration of the 2nd, 3rd and 4th fingers bilaterally, accompanied by localised sensory loss. Petechiae were also seen distributed across the digital pulp and nailbeds. Although bilateral, the left side was notably worse, with clear evidence of digital ischaemia and dry gangrene. Urine dipstix was bland. Immunology revealed normal C3/C4, ANCA and dsDNA serology, but mildly raised ANA (1.5). An echocardiogram excluded infective emboli. High dose IV methylprednisolone and iloprost infusion was commenced to treat ICI-associated peripheral vasculitis. Concurrently, dalteparin was required for a non-occlusive right subclavian venous thrombus. Nevertheless, his digital ischaemia progressed proximally to the left middle distal phalanx. MDT decision was made to avoid Cyclophosphamide given the infection risk. Sildenafil was introduced alongside a reduction regime of oral prednisolone. Unfortunately, the patient was subsequently hospitalised for acute PCP infection requiring high flow oxygen and intravenous antimicrobials. Following this stormy course, a slow but consistent and substantial clinical improvement was noted with respect to his digital ischaemia with minimal tissue loss. 7 months on, the patient’s digits remain free from ischaemia, infection and pain with good functional ability on Sildenafil treatment.

Results
Reports of PD-1 blockade-associated vasculitides mention ANCA-vasculitis, IgA vasculitis, leukocytoclastic vasculitis, eGPA and granulomatous vasculitis; however, drug-induced digit necrosis and auto-amputation is not widely reported. In this rare presentation of digital gangrene, immediate discontinuation of nivolumab treatment with initiation of high dose steroids and sildenafil, allowed eventual recovery of digits with limited auto-amputation and minimal sequelae. Management of nivolumab-associated vasculitis and pneumonitis required a multidisciplinary approach involving oncology, rheumatology, plastics and respiratory medicine. In the context of nivolumab discontinuation, the patient remains only on symptomatic treatment and follow up with no active cancer therapy meaning that prognosis is poor, in keeping with other reports of vasculitic reactions to nivolumab in cancer patients.

Conclusion
ICIs have revolutionised the management and outcomes across a range of malignancies. However, their mechanism can inadvertently induce undesired toxicity, the awareness of which is paramount.
Disclosure
M. Au: None. A. Faher: None. E. Htut: None.