Ivermectin-induced ANCA vasculitis

Introduction: Ivermectin is an antiparasitic agent that has demonstrated antiviral potential against HIV1, Dengue, Zika viruses and most recently, COVID-19. But the rampant self-medication and off-label use for COVID prophylaxis in some countries is cause for concern. Here, we present what may be the first reported case of ANCAassociated vasculitis(AAV)from Ivermectin use. Case Description: A 56-year male with no significant past medical history presented with dark urine, epistaxis, conjunctival redness, arthralgias, and malaise. His mother was on dialysis for the past few years for ESRD of unknown etiology. For several months, he had been taking Ivermectin imported from Peru for COVID prophylaxis per family advice. He was on no other medications. His creatinine, normal at baseline, was now 4.5mg/dL. He had hematuria, 3g/d proteinuria, dysmorphic RBCs and RBC casts. Serum C3, C4, ANA, anti-dsDNA, anti-GBM, hepatitisB&C screen, SPEP&UPEP were negative. Atypical and p-ANCA were negative, but c-ANCA was 1:640. Kidney biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis. He soon developed pulmonary hemorrhages. Ivermectin was discontinued. He received prednisone 1mg/kg, 3 biweekly doses of intravenous cyclophosphamide, 10 doses of plasmapheresis, and was initiated on dialysis. Four weeks later, he has no epistaxis or pulmonary hemorrhages and is off oxygen. He does remain dialysis-dependent. Discussion: Drug exposure can trigger ANCA formation against myeloperoxidase(MPO) and, less commonly, proteinase 3(PR3). Drug-associated AAV can't be discerned from primary AAV based on clinical and pathological findings. Clues suggesting drug-associated AAV include a temporal relationship of symptom onset with suspected drug, a high ANCA titer, and positive autoantibodies like elastase and lactoferrin. Drug-associated AAV has a better prognosis than its primary counterpart, with symptoms often resolving with drug withdrawal. Though this may not suffice in cases with pulmonary and renal involvement, outcomes in drug-associated AAV remain comparable even with shorter induction and often no maintenance regimens. Commonly implicated drugs are hydralazine, levamisole-contaminated cocaine, propylthiouracil, allopurinol. Although no case of Ivermectin-induced AAV has been reported, we recommend a high index of suspicion as prompt cessation of the offending drug can significantly improve prognosis in drug-associated AAV.