B43-43 A Case of Double-Positive Disease

Abstract Introduction Double-positive disease (DPD), characterized by concurrent antiglomerular basement membrane (anti-GBM) and antineutrophil cytoplasmic antibodies (ANCA), represents a unique overlap syndrome with features of both anti-GBM disease and ANCA-associated vasculitis (AAV). Despite growing recognition, management remains guided by single-positive disease guidelines. We present a rare case of a double-positive patient who initially presented with renal failure and later developed pulmonary hemorrhage with ultimate remission with adjunctive rituximab. Case Presentation A 66-year-old man with hypertension, hyperlipidemia, and MPO ANCA-positive interstitial lung disease presented with one month of fatigue. Labs showed creatinine 14.6 mg/dL (baseline 0.78), potassium 7.6 mmol/L, and hemoglobin 7.1 g/dL. Urinalysis revealed proteinuria and hematuria. High-dose steroids were started for suspected AAV-associated rapidly progressive glomerulonephritis requiring urgent dialysis. Autoimmune testing confirmed both MPO-ANCA and anti-GBM antibodies, prompting a 10-day course of plasmapheresis. Renal biopsy showed linear IgG staining, necrotizing crescentic glomerulonephritis, and global sclerosis. Despite transfusion-dependent anemia, initial bronchoscopy showed no pulmonary hemorrhage. The patient developed atrial fibrillation with rapid ventricular response, thus plasmapheresis was held. Two days after the first bronchoscopy, he developed respiratory failure; repeat bronchoscopy confirmed pulmonary hemorrhage. Oral cyclophosphamide was initiated, followed by rituximab two days later. Over the next week, antibody titers declined, pulmonary status improved, and he was discharged on dialysis with a steroid taper and plans for completion of cyclophosphamide and outpatient initiation of maintenance rituximab. Discussion DPD is an uncommon but clinically significant disease with variable presentation and prognosis. Patients often exhibit features of both anti-GBM disease, which carries a high risk of irreversible renal failure, and AAV, which is more prone to relapse. Our patient’s progression from isolated renal involvement to delayed pulmonary hemorrhage highlights the unpredictable and evolving nature of DPD. Standard management includes corticosteroids, cyclophosphamide, and plasmapheresis; however, optimal therapy remains uncertain, especially for refractory or relapsing cases. Rituximab, effective in AAV, has emerging evidence as an alternative or adjunctive therapy in DPD. In our case, rituximab was introduced early alongside cyclophosphamide after pulmonary hemorrhage, with subsequent stabilization. This supports prior reports suggesting a role for rituximab in promoting sustained remission and mitigating relapse risk. This case emphasizes the importance of early recognition, close pulmonary monitoring even in initially renal-limited presentations, and individualized therapy incorporating B-cell-targeted agents. Further studies are needed to define the role of rituximab in induction and maintenance regimens for double-positive patients. This abstract is funded by: None