Pulmonary-Renal Syndrome in a Perineuclear ANCA-Positive Patient: Microscopic Polyangiitis, Lupus Nephritis, or Both?

Introduction: The coexistence of microscopic polyangiitis (MPA) and lupus nephritis (LN) is rare and presents diagnostic challenges. While LN typically features positive anti-dsDNA antibodies and low complement levels, some patients may also test positive for perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA), a marker more commonly associated with MPA suggesting a possible overlap syndrome. Case Description: A 62-year-old man with hypertension presented with tachypnea, oliguria, hemoptysis, and hematuria. Labs showed hemoglobin 6.6 g/dL, creatinine 10.0 mg/dL (baseline 1.0), and 4+ blood on urinalysis. He required red blood cell transfusion, urgent hemodialysis, and intubation for diffuse alveolar hemorrhage confirmed by bronchoscopy. Concern for pulmonary-renal syndrome prompted an autoimmune workup, which revealed positive ANA (1:2560), low complement levels (C3: 58, C4: 7 mg/dl), and P-ANCA (1:160); anti-dsDNA was initially negative. Pulse-dose steroids and rituximab were started, given concern for MPA. The patient was extubated after seven days but remained dialysis-dependent. After stabilization, kidney biopsy revealed diffuse proliferative glomerulonephritis with immune complex deposition and crescents, consistent with Class IV lupus nephritis (LN); however, this did not rule out concurrent P-ANCA-associated microscopic polyangiitis (MPA), given the overlapping histopathologic features that can occur in overlap syndromes. He was discharged on maintenance hemodialysis, prednisone, and mycophenolate mofetil. Repeat testing later showed positive dsDNA titers. It remained uncertain whether this was MPA, LN, or an overlap Discussion: This case illustrates the diagnostic challenges of pulmonary-renal syndrome with overlapping features of microscopic polyangiitis and lupus nephritis. Although P-ANCA positivity and pulmonary hemorrhage suggested vasculitis, low complement levels, immune complex deposition, and later dsDNA positivity supported a diagnosis of Class IV LN. Renal biopsy was essential in guiding treatment. The presence of P-ANCA in LN may indicate more severe disease and highlights the need for early biopsy, close follow-up, and multidisciplinary care. This case emphasizes the importance of considering autoimmune overlap syndromes when clinical and serologic findings are mixed.