A Case of Polyangiitis Overlap Syndrome with MPO-ANCA–Positive Microscopic Polyangiitis and Eosinophilic Granulomatosis with Polyangiitis

Introduction: Among antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA) represent distinct clinical entities. Nevertheless, a small subset of patients manifests overlapping features of these conditions, known as polyangiitis overlap syndrome (POS). Previously reported cases of ANCA-associated POS have primarily involved EGPA and GPA with proteinase-3/cytoplasmic-ANCA positivity. Here, we describe an unusual case of myeloperoxidase (MPO)–ANCA–positive POS with overlapping features of EGPA and MPA.

Case Description: A 60-year-old woman was referred to our hospital for evaluation of progressive renal dysfunction. She had a 15-year history of type 2 diabetes mellitus complicated by retinopathy, treated with oral hypoglycemic agents, and had exhibited intermittent proteinuria for over a decade. Two months prior to admission, she developed progressive lower-limb weakness, myalgia, and exertional dyspnea. Laboratory tests at a local hospital revealed elevated inflammatory markers and interstitial pneumonia, for which antibiotic therapy was ineffective. Her renal function continued to deteriorate, and MPO-ANCA elevated to 1,675 U/mL, prompting referral for suspected AAV. On admission, her Birmingham Vasculitis Activity Score (BVAS) was 18 (muscle pain +1, weight loss ≥ 2 kg +2, purpura +2, wheeze +1, proteinuria +4, serum creatinine 1.4–2.79 mg/dL +4, > 30% increase in creatinine +6). Laboratory results showed CRP 9 mg/dL, eosinophils 25%, and CH50 53 U/mL; eosinophils were also present in the urine sediment. Renal biopsy demonstrated marked eosinophilic and plasma cell infiltration in the tubulointerstitial area with fibrinoid necrosis. Immunofluorescence microscopy revealed a pauci-immune pattern. According to the 2022 ACR/EULAR classification criteria, she scored 8 points for MPA (MPO-ANCA +6, interstitial pneumonia +3, pauci-immune glomerulonephritis +3, eosinophils ≥ 1,000/μL −4) and 9 for EGPA (obstructive airway disease +3, eosinophils ≥ 1,000/μL +5, extravascular eosinophilic inflammation on biopsy +2, hematuria −1), supporting the diagnosis of overlapping EGPA and MPA. She was treated with intravenous methylprednisolone 500 mg/day for 3 days, followed by oral prednisolone 30 mg/day (0.6 mg/kg). By day 7, her 24-hour urinary protein decreased to 0.34 g/day and microscopic hematuria resolved. By day 12, BVAS decreased to 2. Given her clinical stabilization and improved renal function, she was discharged without additional immunosuppressive therapy.

Discussion: Previous reports of MPO-ANCA-positive POS generally describe modest ANCA titers and require combined immunosuppressive therapy for remission. In contrast, our patient achieved rapid remission with corticosteroid monotherapy despite extremely high MPO-ANCA levels. The absence of peripheral neuropathy and lack of serum interleukin-5 elevation, coupled with the presence of interstitial pneumonia, were atypical for EGPA. These findings suggest that the dominant pathogenic process may have resembled MPA rather than classical EGPA, or that alternative humoral mediators beyond IL-5 contributed to the disease activity.