A Double-Edged Sword: The Clinical Dilemma of Lupus Nephritis and Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome

Lupus nephritis (LN) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are classically regarded as distinct autoimmune diseases with differing pathophysiologic mechanisms-immune complex-mediated injury in LN versus pauci-immune necrotizing vasculitis in AAV. However, recent studies have identified a rare but emerging overlap syndrome characterized by dual serologic, histopathologic, and clinical features. This diagnostic entity presents unique challenges, particularly in older adults with rapidly progressive glomerulonephritis (RPGN) and systemic inflammation. We describe a diagnostically challenging case of a 74-year-old woman with a history of interstitial lung disease, polyarthritis, and sicca symptoms who developed new-onset hemoptysis, peripheral neuropathy, and acute kidney injury. She underwent an extensive workup, which revealed hypocomplementemia, high-titer antinuclear antibody (ANA), and seropositivity for Sjögren's-syndrome-related antigen A (SSA/Ro) and ribonucleoprotein (RNP) antibodies, along with markedly elevated myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) levels. These findings raised concern for dual autoimmune pathology. Laboratory evaluation additionally demonstrated worsening kidney function, proteinuria, and microscopic hematuria, prompting a renal biopsy. Histologic examination revealed class IV LN, characterized by diffuse immune complex deposition, as well as necrotizing crescentic glomerulonephritis, a hallmark of pauci-immune AAV. These overlapping serologic and histopathologic features, in the context of pulmonary hemorrhage, were diagnostic of LN-AAV overlap syndrome. The patient was treated with aggressive immunosuppressive therapy, resulting in improvement of renal function and resolution of systemic symptoms. This case underscores the importance of maintaining a high index of suspicion for overlapping autoimmune phenomena in elderly patients with atypical serologic and histopathologic findings. Early recognition is essential to initiate appropriate therapy and improve outcomes in this complex clinical setting.