Myeloperoxidase anti-neutrophil cytoplasmic antibody vasculitis mimicking renal polyarteritis nodosa

A 35-year-old woman, with no previous medical history, was admitted to our nephrology department for proteinuria and microscopic hematuria. On presentation, she complained of asthenia, weight loss, fever, and dyspnea persisting for two months. Initial laboratory tests showed C-reactive protein 283 mg/L, hemoglobin 6.8 g/dL, serum creatinine 76 µmol/L, 71 red blood cells/mm3 on cytological urine analysis, and urine protein/creatinine ratio 1.7 g/g. Thoracic computed tomography (CT) identified peribronchial condensation, and a bronchial biopsy showed inflamed and ulcerated mucosa without granuloma. Immunological examination showed positive anti-myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) (128 UI/ mL Elia), compatible with lung involvement, which was highly suggestive of pulmonary vasculitis. Given the urinary abnormalities, necrotizing glomerulonephritis was suspected and a left kidney biopsy was performed. Light microscopy showed diffuse cortical necrosis with normal medulla (Figure 1A), and frozen section biopsies showed 8 normal glomeruli without immune deposits. A contrast-enhanced CT scan showed multiple right and left renal infarcts with microaneurysms (Figure 1B and C). Given the atypical presentation for ANCA-associated vasculitis (AAV), extensive investigations revealed negative bacterial blood cultures, absence of antiphospholipid antibodies (anticardiolipin, anti-β2-glycoprotein 1, and lupus anticoagulant), negative urine toxicology, negative hepatitis B serology, normal transesophageal echocardiography, and no significant hypermetabolism on 18F-FDG PET/CT. (A) Light microscopy, kidney biopsy, total cortical necrosis characterized by ischemic necrosis of all renal tissue structures: glomeruli (star), tubules (arrow), vessels (arrow) and interstitium (periodic acid–Schiff stain, original magnification ×100). (B) Arterial phase of an abdominal computed tomography scan reveals bilateral renal defects, indicative of renal infarction and a splenic infarct. (C) Right kidney exhibiting renal infarction (arrow head) with microaneurysms (arrow) observed during the portal phase along with left renal hematoma (star). (D) Spontaneous right renal hematoma (star). Eight days later, the patient developed left lumbar pain, and CT scan identified a left renal hematoma (11 cm) with active arterial bleeding, confirmed by arteriography, which also showed bilateral renal microaneurysms. This renal hemorrhage was deemed a complication of the kidney biopsy. Two days later, she developed right lumbar pain; CT scan identified a spontaneous hematoma in the right kidney, attributed to the rupture of an arterial microaneurysm (Figure 1D). The final diagnosis was AAV mimicking polyarteritis nodosa (PAN). Glucocorticoids (70 mg/day) and rituximab (1000 mg, two doses 15 days apart) were initiated three days after the onset of the right renal hematoma, leading to significant clinical improvement and regression of pulmonary involvement. However, residual kidney impairment persisted, with a serum creatinine level of 150 µmol/L. The disease course was complicated by acute respiratory distress syndrome secondary to COVID-19 pneumonia, occurring four months after completion of the final maintenance rituximab infusion (500 mg every 6 months for 4 infusions). At the last follow-up, 3.5 years after the initial diagnosis, the patient remained relapse-free with serum creatinine level of 208 μmol/L and negative MPO-ANCA. The 2012 International Chapel Hill Consensus Conference classified vasculitides based on distinct vessel size involvement. PAN is the main variant of medium-vessel vasculitis in adults, affecting the main visceral arteries and their branches, and is characterized by necrotizing arteritis of medium or small arteries without glomerulonephritis or involvement of arterioles, capillaries, or venules.1,2 Prior to the discovery of ANCAs, clinical overlap between microscopic polyangiitis and PAN led to confusion between these entities.1 The absence of ANCAs is mandatory for diagnosing PAN, and MPO-ANCA is the hallmark of microscopic polyangiitis.1 The kidney is commonly involved in PAN (26–44%)3 and AAV (60%),4 however, the patterns of kidney damage differ significantly between these vasculitides. Kidney involvement in PAN is characterized by vasculitis of the renal and interlobar arteries, leading to tissue infarction, microaneurysm formation, and hematomas,3 whereas AAV primarily targets glomerular capillaries, resulting in necrotizing pauci-immune glomerulonephritis.5 Although rare, aneurysms may also occur in AAV, predominantly involving renal arteries.6 This case illustrates that MPO-ANCA-associated vasculitis may closely mimic PAN's renal features, including renal infarctions, microaneurysms, normal glomeruli on kidney biopsy, and spontaneous renal hematomas. None. Charles Ronsin: conceptualization, data curation, writing original draft, review and editing; Anne Moreau: data curation, resources, writing original draft; Maxence Laot: data curation, resources, writing original draft; Grégoire Couvrat-Desvergnes: writing original draft; Marion Chapal: data curation, writing original draft; review and editing. None declared. Not applicable. Not needed. Informed consent has been obtained from the patient.