PR3-ANCA–ASSOCIATED VASCULITIS WITH ELEVATED IgG4 AND RETROPERITONEAL FIBROSIS: A DIAGNOSIS AND THERAPIUTIC CHALLENGE

ANCA-associated vasculitis (AAV) typically presents with pauci-immune necrotizing (GN) and systemic inflammation. Retroperitoneal fibrosis (RPF) is rarely associated with AAV and more commonly linked to IgG4-related disease (IgG4-RD). We report a rare case of PR3-ANCA–positive AAV with RPF and elevated IgG4, highlighting diagnostic complexity and therapeutic response.

A 66-year-old man was referred for progressive renal dysfunction. Three years earlier, he had been diagnosed with left-sided RPF and hydronephrosis, with stable renal function and normal IgG4. At referral, creatinine had risen from 1.14 to 3.35 mg/dL. He had lost 7 kg over six months and presented with scleritis and chronic rash. Labs showed CRP 1.78 mg/dL, PR3-ANCA >350 U/mL, and IgG4 418 mg/dL. CT and PET-CT revealed left hydronephrosis, parenchymal thinning, and retroperitoneal uptake. No abnormal accumulation was seen in salivary glands or pancreas. Due to solitary kidney and diagnostic uncertainty, an open biopsy of the right kidney was performed.

Biopsy revealed 60 glomeruli, with 10 showing necrotizing cellular or fibro-cellular crescents. Up to 80% of interstitial plasma cells were IgG4-positive, but storiform fibrosis was absent. Immunofluorescence and electron microscopy showed no significant immune deposits. These findings supported a diagnosis of pauci-immune crescentic GN consistent with AAV. Treatment included half-pulse methylprednisolone, oral prednisolone (60 mg/day), and two doses of rituximab. On day 18, the patient developed left foot drop. Nerve conduction studies confirmed mononeuritis multiplex. A second steroid pulse and avacopan were added, leading to improvement in neurological symptoms, scleritis, skin lesions, urinary findings, and imaging, including RPF and hydronephrosis.

This case illustrates the rare coexistence of PR3-ANCA–positive AAV and retroperitoneal fibrosis (RPF) with elevated IgG4. Although IgG4-RD was initially considered, the absence of storiform fibrosis and the presence of necrotizing crescentic GN supported a diagnosis of AAV. The retroperitoneal lesion was not biopsied, but its regression following immunosuppressive therapy suggests that it may have represented vasculitis-related inflammatory enlargement, with ureteral obstruction resolving as inflammation subsided. The patient also developed mononeuritis multiplex, which was interpreted as part of the systemic vasculitic process and responded to intensified immunosuppression.

While PR3-ANCA titers were markedly elevated at diagnosis, the preceding three-year clinical course following the diagnosis of retroperitoneal fibrosis had been relatively indolent until a turning point marked by the onset of systemic fatigue. It is possible that the smoldering phase was influenced by the IgG4 subclass of PR3-ANCA, which may attenuate inflammatory amplification by limiting IL-8–mediated neutrophil recruitment. The mechanism triggering the disease burst remains unclear. This case highlights the importance of integrating histopathology, imaging, and clinical context to guide diagnosis and treatment in atypical presentations of AAV. Open renal biopsy was essential for accurate diagnosis and therapeutic decision-making.