A Rare Diagnostic Dilemma of P-ANCA/MPO Positive Crescentic Glomerulonephritis in an Immunosuppressed Lupus Patient.

Perinuclear antineutrophil cytoplasmic antibodies (P-ANCAs) and myeloperoxidase (MPO) antibodies are detected in 15%-25% of lupus nephritis patients, but systemic lupus erythematosus (SLE)/ANCA-associated vasculitis (AAV) overlap syndrome is rare, occurring in approximately 2% of cases. We present a 57-year-old woman with SLE and antiphospholipid syndrome (APS) on belimumab, hydroxychloroquine, and prednisone, who presented with acute ischemic stroke requiring thrombectomy and rapidly progressive renal failure (creatinine rising from 1.1 to 5.2 mg/dL) with nephrotic-range proteinuria (8.6 g/g). P-ANCA titer was > 1:640 with MPO positivity, while anti-dsDNA, C3, and C4 were normal. Kidney biopsy revealed crescentic glomerulonephritis with neutrophil-rich infiltrates and immune complex deposits on electron microscopy but without "full house" immunofluorescence, favoring SLE/AAV overlap rather than isolated lupus nephritis flare. Treatment with methylprednisolone, rituximab, and anticoagulation resulted in significant renal recovery (creatinine 1.7 mg/dL, proteinuria 4.4 g/g). This case highlights the importance of ANCA testing in SLE patients with unexplained rapidly progressive glomerulonephritis, as early recognition of overlap syndrome carries distinct therapeutic implications, including the use of rituximab-based regimens targeting both disease processes.