Abstract Introduction The co-occurrence of IgA nephropathy (IgAN) and anti-neutrophil cytoplasmic antibody (ANCA) seropositivity is rare, and the overlap with drug- or infection-induced ANCA syndromes presents a significant diagnostic challenge. Distinguishing true ANCA-associated vasculitis from mimics is critical, as management and prognosis differ substantially. Case Presentation A 74-year-old male with chronic obstructive pulmonary disease, diabetes, chronic kidney disease, cocaine use disorder, Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, and chronic lower extremity ulcers presented with acute hypoxemic respiratory failure, multifocal pneumonia, and septic arthritis. Laboratory evaluation revealed proteinase 3-ANCA (PR3-ANCA) positivity (8.0 units), negative myeloperoxidase-ANCA (MPO-ANCA) (0.2 AI), p-ANCA pattern on immunofluorescence (1:320), and negative antinuclear antibody (ANA), anti-double-stranded deoxyribonucleic acid antibody, and rheumatoid factor with normal complement levels. Urinalysis demonstrated heavy proteinuria with elevated protein-to-creatinine ratio but no active sediment. Sputum cultures grew Escheria coli and MRSA.Chest CT showed multifocal pneumonia, bilateral airspace opacities, including cavitary lesions (largest measuring 9.1 × 4.5 cm). Renal biopsy demonstrated nodular glomerulosclerosis and IgAN without pauci-immune crescentic glomerulonephritis. Nasal CT revealed prior nasal septal perforation; nasal biopsy showed mild chronic inflammation, lacking granulomas or vasculitic changes. The patient was managed with vancomycin, meropenem, and empiric prednisone which was discontinued following results of nasal biopsy. Discussion The presence of PR3-ANCA positivity, cavitary lung lesions, nasal septal perforation, and renal involvement in this patient suggests a diagnosis of ANCA-associated vasculitis, yet the absence of pauci-immune necrotizing and crescentic glomerulonephritis on biopsy ruled against granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). In the absence of biopsy confirmation, PR3-ANCA positivity was likely falsely positive in the setting of infection.The co-occurrence of IgAN and PR3-ANCA positivity is rare, as most cases of ANCA-positive IgAN involve MPO-ANCA and present with crescentic rapidly progressive glomerulonephritis. In the largest published series, only 1.2% of biopsy-proven IgAN cases had ANCA positivity, and these overlap cases typically showed histologic features of vasculitis. To date, there are no published reports describing the combination of cocaine-induced midline destructive lesions, PR3-ANCA positivity, and IgAN. The histopathology in this case aligns with IgA-dominant infection-related glomerulonephritis, a well-described entity in elderly, diabetic patients with chronic staphylococcal infection.Cocaine use and chronic infections can induce ANCA seropositivity and produce clinical syndromes that closely mimic primary ANCA-associated vasculitis but often lack histologic evidence of true vasculitis; distinguishing these mimics from genuine ANCA-associated vasculitis is essential to avoid adverse effects from steroid use. This abstract is funded by: NONE
Elsawy et al. (Fri,) studied this question.