Coexistence of ANCA-Associated Vasculitis and Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits: A Diagnostic and Treatment Dilemma

Introduction: Proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID), is a manifestation of monoclonal gammopathy of renal significance (MGRS), characterized by monoclonal immunoglobulin deposition, most commonly IgG3 kappa in the glomeruli. In contrast, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a pauci-immune small-vessel vasculitis with minimal immune complex deposition. Their coexistence is exceptionally rare and presents a diagnostic and therapeutic challenge. Case Description: A 63-year-old Hispanic male presented with a 3-month history of hemoptysis, 15-pound unintentional weight loss and a non-blanching maculopapular rash. Physical examination revealed tongue ulcers, swollen joints, and bilateral skin lesions. Laboratory tests showed PR3-ANCA >8 U/mL, positive rheumatoid factor, serum creatinine 0.74 mg/dL. Urinalysis showed 3+ blood and 1+ protein with a urine protein-to-creatinine ratio of 1 g/g. Serum protein electrophoresis revealed polyclonal gammopathy without a monoclonal spike; serum myeloperoxidase was negative. Renal biopsy was performed. Light microscopy demonstrated focal segmental necrotizing and crescentic glomerulonephritis, consistent with AAV. Immunofluorescence revealed mesangial IgG3 κ-restricted granular electron-dense deposits and mesangial hypercellularity consistent with PGNMID. Absence of a detectable peripheral clone further complicated the treatment approach. Induction therapy with IV methylprednisolone and rituximab was initiated, followed by oral prednisone taper. The patient showed symptomatic improvement with declining PR3 titers and reduction in proteinuria. Discussion: This case illustrates a rare and diagnostically challenging overlap between PGNMID and AAV. The precise pathophysiological relationship between these entities remains unclear—whether they arise from distinct mechanisms or reflect a shared underlying immune dysregulation. Currently, there are no established guidelines for the management of coexisting PGNMID and AAV. Given the rarity and clinical complexity of this presentation, further research is essential to elucidate the underlying mechanisms to develop evidence-based therapeutic strategies.