Diffuse alveolar hemorrhage in rheumatic diseases: Clinical features, diagnosis, and management

Abstract Diffuse alveolar hemorrhage (DAH) is a catastrophic pulmonary manifestation of systemic autoimmune and rheumatic diseases, particularly systemic lupus erythematosus (SLE), ANCA-associated vasculitis (AAV), and antiphospholipid syndrome (APS). It arises from immune-mediated injury to the pulmonary microcirculation, leading to intra-alveolar bleeding, respiratory failure, and high mortality. Despite advances in immunosuppression, DAH continues to pose major diagnostic and therapeutic challenges, with limited consensus on optimal management. We conducted an updated and comprehensive review of the epidemiology, pathogenesis, clinical spectrum, diagnostic strategies, therapeutic approaches, and outcomes of DAH in the context of rheumatic diseases through PubMed, Embase, and Scopus databases up to March 2025. DAH occurs in approximately 2%–5% of patients with SLE and up to 55% of patients with AAV, with reported mortality rates ranging from 20% to 80%. Hemoptysis is present in fewer than half of cases, highlighting the need for a high index of suspicion in patients presenting with anemia, dyspnea, and new bilateral infiltrates. Imaging typically reveals ground-glass opacities and consolidations on high-resolution CT, with a “crazy-paving” pattern observed during resolution. Bronchoscopy with bronchoalveolar lavage remains the diagnostic gold standard, confirming hemorrhage in sequential lavage aliquots. Histopathology demonstrates either pulmonary capillaritis or bland hemorrhage, with up to 73% of lupus-associated DAH cases showing the latter pattern without overt vasculitis. First-line therapy includes high-dose corticosteroids, frequently combined with cyclophosphamide or rituximab, while plasma exchange and intravenous immunoglobulin are considered in refractory disease. The PEXIVAS trial has challenged the universal role of plasma exchange, though it may retain a role in select patients with concomitant renal failure. Emerging therapies, such as complement inhibitors, B-cell targeted therapies, and mesenchymal stem cell transplantation, are under investigation. Supportive measures, including oxygen supplementation, noninvasive or invasive ventilation, and infection prophylaxis, are integral to management. Long-term survivors are at risk of recurrent hemorrhage and interstitial fibrosis. In conclusion, by consolidating current evidence and highlighting existing gaps, this review provides a clinically relevant framework to guide diagnosis, management, and future directions in the care of patients with DAH associated with rheumatic diseases.