Unexpected adverse event caused by avacopan: a case of drug-induced hypersensitivity syndrome in microscopic polyangiitis

Microscopic polyangiitis (MPA) is an antineutrophil cytoplasmic antibody-associated vasculitis characterised by inflammation in small vessels. Avacopan, an oral C5a receptor inhibitor, has demonstrated efficacy in inducing and sustaining remission in MPA, with the added benefit of reducing glucocorticoid exposure and associated toxicities. Among adverse effects, liver injury is the most common, occurring in 16.7-40.9% of cases in the Japanese cohorts. Drug-induced hypersensitivity syndrome (DIHS) is a rare adverse effect caused by avacopan. We describe a case of a 77-year-old woman with MPA who was initiated on prednisolone 30 mg/day and avacopan as the induction therapy. Disease activity of MPA improved with this induction therapy. However, 7 weeks after initiating avacopan, she developed significant liver dysfunction. Despite the discontinuation of avacopan, she subsequently presented with fever and a generalised rash, leading to a diagnosis of DIHS. Laboratory data revealed reactivation of human herpesvirus 6. Despite the discontinuation of avacopan, liver injury persisted, and liver biopsy findings were consistent with drug-induced hepatitis. Long-term hospitalisation was required for improvement in skin symptoms and liver function. This case highlights a rare but serious adverse event of avacopan in MPA. During avacopan therapy, it is necessary to monitor for delayed severe skin symptoms such as DIHS.