Abstract Introduction Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening manifestation of antiphospholipid antibody syndrome (APS), occurring in 1% of patients. It reflects antibody-mediated microvascular injury within the lung microenvironment, often manifesting as pulmonary capillaritis. The 2019 Current Rheumatology Reports review noted that among them, capillaritis is observed in only ∼30-50% of biopsies, and that remission is most effectively achieved with rituximab or cyclophosphamide (∼50%). We report a rare case of biopsy-proven APS-associated pulmonary capillaritis causing DAH, successfully treated with B-cell depletion therapy leading to sustained, steroid-sparing remission. Case Presentation A 45-year-old woman with APS (history of DVT, Budd-Chiari syndrome, portal vein thrombosis s/p venoplasty, on warfarin), SLE, IgA nephropathy, and prior heparin-induced thrombocytopenia presented with progressive cough and hypoxemia. CT chest showed bilateral patchy opacities unresponsive to antibiotics. Right-sided VATS wedge biopsy revealed diffuse intra-alveolar hemorrhage with neutrophilic capillaritis and hemosiderin-laden macrophages, consistent with APS-associated pulmonary capillaritis. Serology demonstrated positive ANA and p-ANCA (MPO-negative), but the histopathologic pattern and clinical context supported APS as the primary etiology of the pulmonary vasculitis. She received pulse-dose methylprednisolone followed by rituximab (1 g × 2 doses, 2 weeks apart) and a prednisone taper. Her course was complicated by COVID-19 pneumonia, treated with remdesivir, after which rituximab was resumed. She remains clinically stable on 15 mg prednisone, with no recurrent hemoptysis and improved functional status. Discussion This case underscores APS-associated pulmonary capillaritis as a distinct cause of DAH, independent of concomitant autoimmune disease. Lung biopsy confirmed immune-mediated endothelial injury without thrombosis, consistent with antiphospholipid antibody-driven capillaritis. The patient’s course reflects autoantibody-mediated endothelial damage and complement activation, disrupting the alveolar-capillary microenvironment and leading to intra-alveolar bleeding. Rituximab achieved durable, steroid-sparing remission, aligning with published response rates and reinforcing its role as targeted immunotherapy in refractory APS-DAH. Conclusion Biopsy confirmation established APS-associated pulmonary capillaritis as the cause of DAH, guiding the use of B-cell-directed immunotherapy. Rituximab achieved long-term remission and corticosteroid tapering, emphasizing the importance of early tissue diagnosis and targeted therapy in antibody-mediated pulmonary vascular injury. This abstract is funded by: None
Kancharla et al. (Fri,) studied this question.