RARE DISEASE
Diffuse alveolar hemorrhage
Diffuse alveolar hemorrhage
Diffuse alveolar hemorrhage
Drug discovery
2
drugs
With orphan designations
Overview
Diffuse alveolar hemorrhage (DAH) is a life-threatening syndrome marked by intra-alveolar bleeding, often secondary to autoimmune disorders (e.g., vasculitis, systemic lupus erythematosus), coagulation defects, infections, or toxins. Clinical hallmarks include dyspnea, hemoptysis, anemia, and diffuse pulmonary infiltrates. Diagnosis requires bronchoscopy with bronchoalveolar lavage showing progressively bloody fluid. Treatment focuses on immunosuppression (corticosteroids, cyclophosphamide, rituximab) for autoimmune causes, supportive respiratory care, and addressing underlying etiologies. Mortality remains high (20–50%), particularly with shock, renal failure, or delayed intervention [1][2][5][14].
Therapies
High-dose corticosteroids (e.g., methylprednisolone) and immunosuppressants (cyclophosphamide, rituximab) [1][3][5].
Plasma exchange for Goodpasture syndrome or severe vasculitis [1][11].
Recombinant factor VIIa or antifibrinolytics in refractory cases; invasive ventilation for respiratory failure [3][7][11].
Categories: rare respiratory diseases
Research Papers
643 drug discovery papers about Diffuse alveolar hemorrhage, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
643 drug discovery papers about Diffuse alveolar hemorrhage, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-12 | Diffuse Alveolar Hemorrhage Following Trauma: A Diagnostic Dilemma With Rapid Steroid Response.
Diffuse alveolar hemorrhage (DAH) is a rare but potentially life-threatening pulmonary condition that, while classically linked to autoimmune disorders, can occur in the setting of trauma. We report the case of a 20-year-old male who sustained polytrauma following a road traffic accident and initially had a normal chest radiograph. On the fourth day of hospitalization, he developed acute hypoxemia with new bilateral alveolar infiltrates; high-resolution computed tomography revealed diffuse ground-glass opacities with septal thickening. Bronchoalveolar lavage demonstrated progressively hemorrhagic return across aliquots, confirming DAH. Autoimmune markers were largely negative, and in the absence of systemic features, a multifactorial etiology involving trauma-related injury and anticoagulant use was considered. High-dose intravenous corticosteroids produced rapid clinical and radiological recovery. This case underscores the importance of considering DAH in trauma patients presenting with unexplained hypoxemia and bilateral infiltrates, even without hemoptysis, where early bronchoscopy and prompt treatment can be lifesaving.
2026-08-01 | Diffuse alveolar hemorrhage in ANCA-associated vasculitis: Current evidence and multimodal treatment approaches.
Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with management largely extrapolated from broader AAV and ARDS literature. We conducted a review of studies published between 2000 and 2025 evaluating treatments and outcomes in AAV-associated DAH, synthesizing evidence across immunosuppressive, plasmapheresis, hemostatic, respiratory and hemodynamic, and infection prevention strategies. Glucocorticoids combined with rituximab or cyclophosphamide induce remission in most patients, although optimal steroid tapering and comparative efficacy in severe, ventilated DAH remain uncertain. Avacopan improves sustained remission and renal recovery in severe AAV and appears to be a feasible steroid-sparing adjunct in early DAH series. Large randomized trials demonstrate no survival benefit of plasma exchange. Local hemostatic therapies may provide rapid bleeding control, but evidence is limited. Respiratory outcomes are driven by hypoxemia severity and need for invasive ventilation or extracorporeal support. Lastly, infection prevention measures are strongly supported.
2026-07-28 | MEK/ERK Mediated Diffuse Alveolar Hemorrhage in Murine Lupus 2261092
Abstract Introduction About 3% of patients with lupus develop severe diffuse alveolar hemorrhage (DAH) with pulmonary vasculitis. C57BL/6 (B6) mice with pristane-induced lupus also develop DAH, but BALB/c mice are resistant. DAH is independent of Toll-like receptor signaling and other inflammatory pathways. This study examined the role of the MEK1/2 pathway Methods B6 and BALB/c mice were treated with pristane with or without inhibitors of MEK1/2 (trametinib/GSK1120212 [GSK]), ERK1/2 (SCH772984 [SCH]), JNK, or p38. Effects on lung hemorrhage and hemostasis were determined Results GSK and SCH abolished DAH, whereas JNK and p38 inhibitors were ineffective. Apoptotic cells were present in lung samples from pristane-treated mice but not in mice receiving pristane and GSK, and endothelial dysfunction was normalized. Expression of the ERK1/2-regulated transcription factor early growth response 1 increased in pristane-treated B6, but not BALB/c, mice and was normalized by GSK. Pristane also increased expression of the anticoagulant genes Tfpi and Thbd in B6 mice. The ratio of Tfpi to tissue factor (F3) to Tfpi increased in B6 (but not BALB/c) mice and was normalized by GSK. Circulating thrombomodulin protein levels increased in B6 mice and returned to normal after GSK treatment. Consistent with augmented endothelial anticoagulant activity, pristane treatment increased tail bleeding in B6 mice. Conclusion Pristane treatment promotes lung endothelial injury and DAH in B6 mice by activating the MEK1/2-ERK1/2 pathway and impairing hemostasis. The hereditary factors determining susceptibility to lung injury and bleeding in pristane-induced lupus are relevant to the pathophysiology of life-threatening DAH in systemic lupus erythematosus and may help to optimize therapy. Funding Source NIH, University of Florida Gatorade fund Topic Categories Therapeutic Approaches to Autoimmunity (THER)
2026-07-26 | A case report of pregnancy complicated by diffuse alveolar hemorrhage: An unexpected link to untreated Graves' disease.
Diffuse Alveolar Hemorrhage (DAH) is a life-threatening condition characterized by widespread bleeding within the alveoli, often resulting from pulmonary capillaritis, bland pulmonary hemorrhage, or diffuse alveolar damage. It presents with hemoptysis, dyspnea, hypoxemia, and anemia, and can lead to respiratory failure. This case report highlights a rare instance of DAH in a pregnant woman with untreated Graves' disease, emphasizing the importance of considering uncommon etiologies in the absence of typical triggers. A 36-year-old pregnant woman at 37 weeks of gestation presented with hemoptysis and dyspnea. Initial evaluations, including pulmonary CT angiography, ruled out pulmonary embolism but revealed bilateral diffuse alveolar involvement. Bronchoscopy confirmed DAH, with serologic tests indicating hyperthyroidism due to Graves' disease. The patient was treated with pulse methylprednisolone and later methimazole, leading to symptom resolution. She delivered a healthy baby at 40 weeks via uncomplicated vaginal delivery. DAH during pregnancy is rare, and its association with untreated Graves' disease is exceptionally uncommon. In this case, untreated Graves' disease may have contributed to left ventricular diastolic dysfunction, exerting shear stress on pulmonary vasculature and potentially resulting in DAH. The absence of coagulopathy, environmental exposures, or autoantibodies supported this conclusion. This case underscores the need to consider thyroid disorders in the differential diagnosis of bland pulmonary hemorrhage, particularly when other causes are excluded. Early identification and management of underlying causes can significantly improve maternal and fetal outcomes. This report highlights the importance of exploring rare etiologies in cases of DAH, especially in pregnant patients, to ensure timely and effective intervention.
2026-07-10 | Idiopathic Pulmonary Hemosiderosis: A Comprehensive Review of Pathophysiology, Diagnostic Paradigms, and Management Strategies in the Context of Diffuse Alveolar Hemorrhage
Idiopathic pulmonary hemosiderosis (IPH) represents a rare, potentially life-threatening pulmonary syndrome characterized by recurrent episodes of diffuse alveolar hemorrhage (DAH) in the absence of an identifiable underlying etiology. As a diagnosis of strict exclusion within the broader spectrum of DAH, IPH poses substantial diagnostic and therapeutic challenges to clinicians across multiple specialties. This comprehensive review synthesizes current evidence regarding the etiopathogenesis, epidemiology, clinical presentation, diagnostic evaluation, and management of IPH, with particular emphasis on its conceptualization as an immune-mediated disorder and its integration within the contemporary classification of children's interstitial lung disease (chILD). The pathogenesis of IPH remains incompletely elucidated; however, accumulating evidence supports a fundamentally immune-dysregulatory mechanism, with autoantibodies detectable in a significant proportion of patients and well-documented associations with autoimmune conditions, most notably celiac disease, which defines the clinically significant Lane–Hamilton syndrome. The clinical presentation is remarkably heterogeneous, ranging from acute respiratory failure and massive hemoptysis to isolated iron-deficiency anemia without overt pulmonary symptoms, particularly in pediatric populations. Diagnosis requires systematic exclusion of vasculitic, infectious, cardiac, coagulopathic, and toxicologic etiologies through a structured approach encompassing serologic evaluation, bronchoalveolar lavage, high-resolution computed tomography, and, when indicated, lung biopsy demonstrating bland alveolar hemorrhage without capillaritis. Management is predicated upon immunosuppressive therapy, with systemic corticosteroids serving as the cornerstone, augmented by steroid-sparing agents in refractory or relapsing disease, and supplemented by strict gluten-free dietary intervention in patients with coexistent celiac disease. Prognosis has improved substantially in the modern immunosuppressive era, although significant morbidity persists, with relapse rates approaching 60% and progressive pulmonary fibrosis representing a major long-term complication. An interprofessional, collaborative approach involving pulmonology, rheumatology, gastroenterology, and supportive care services is essential to optimize diagnostic accuracy, therapeutic adherence, and longitudinal outcomes in this challenging patient population.
2026-08-12 | Diffuse Alveolar Hemorrhage Following Trauma: A Diagnostic Dilemma With Rapid Steroid Response.
Diffuse alveolar hemorrhage (DAH) is a rare but potentially life-threatening pulmonary condition that, while classically linked to autoimmune disorders, can occur in the setting of trauma. We report the case of a 20-year-old male who sustained polytrauma following a road traffic accident and initially had a normal chest radiograph. On the fourth day of hospitalization, he developed acute hypoxemia with new bilateral alveolar infiltrates; high-resolution computed tomography revealed diffuse ground-glass opacities with septal thickening. Bronchoalveolar lavage demonstrated progressively hemorrhagic return across aliquots, confirming DAH. Autoimmune markers were largely negative, and in the absence of systemic features, a multifactorial etiology involving trauma-related injury and anticoagulant use was considered. High-dose intravenous corticosteroids produced rapid clinical and radiological recovery. This case underscores the importance of considering DAH in trauma patients presenting with unexplained hypoxemia and bilateral infiltrates, even without hemoptysis, where early bronchoscopy and prompt treatment can be lifesaving.
2026-08-01 | Diffuse alveolar hemorrhage in ANCA-associated vasculitis: Current evidence and multimodal treatment approaches.
Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with management largely extrapolated from broader AAV and ARDS literature. We conducted a review of studies published between 2000 and 2025 evaluating treatments and outcomes in AAV-associated DAH, synthesizing evidence across immunosuppressive, plasmapheresis, hemostatic, respiratory and hemodynamic, and infection prevention strategies. Glucocorticoids combined with rituximab or cyclophosphamide induce remission in most patients, although optimal steroid tapering and comparative efficacy in severe, ventilated DAH remain uncertain. Avacopan improves sustained remission and renal recovery in severe AAV and appears to be a feasible steroid-sparing adjunct in early DAH series. Large randomized trials demonstrate no survival benefit of plasma exchange. Local hemostatic therapies may provide rapid bleeding control, but evidence is limited. Respiratory outcomes are driven by hypoxemia severity and need for invasive ventilation or extracorporeal support. Lastly, infection prevention measures are strongly supported.
2026-07-28 | MEK/ERK Mediated Diffuse Alveolar Hemorrhage in Murine Lupus 2261092
Abstract Introduction About 3% of patients with lupus develop severe diffuse alveolar hemorrhage (DAH) with pulmonary vasculitis. C57BL/6 (B6) mice with pristane-induced lupus also develop DAH, but BALB/c mice are resistant. DAH is independent of Toll-like receptor signaling and other inflammatory pathways. This study examined the role of the MEK1/2 pathway Methods B6 and BALB/c mice were treated with pristane with or without inhibitors of MEK1/2 (trametinib/GSK1120212 [GSK]), ERK1/2 (SCH772984 [SCH]), JNK, or p38. Effects on lung hemorrhage and hemostasis were determined Results GSK and SCH abolished DAH, whereas JNK and p38 inhibitors were ineffective. Apoptotic cells were present in lung samples from pristane-treated mice but not in mice receiving pristane and GSK, and endothelial dysfunction was normalized. Expression of the ERK1/2-regulated transcription factor early growth response 1 increased in pristane-treated B6, but not BALB/c, mice and was normalized by GSK. Pristane also increased expression of the anticoagulant genes Tfpi and Thbd in B6 mice. The ratio of Tfpi to tissue factor (F3) to Tfpi increased in B6 (but not BALB/c) mice and was normalized by GSK. Circulating thrombomodulin protein levels increased in B6 mice and returned to normal after GSK treatment. Consistent with augmented endothelial anticoagulant activity, pristane treatment increased tail bleeding in B6 mice. Conclusion Pristane treatment promotes lung endothelial injury and DAH in B6 mice by activating the MEK1/2-ERK1/2 pathway and impairing hemostasis. The hereditary factors determining susceptibility to lung injury and bleeding in pristane-induced lupus are relevant to the pathophysiology of life-threatening DAH in systemic lupus erythematosus and may help to optimize therapy. Funding Source NIH, University of Florida Gatorade fund Topic Categories Therapeutic Approaches to Autoimmunity (THER)
2026-07-26 | A case report of pregnancy complicated by diffuse alveolar hemorrhage: An unexpected link to untreated Graves' disease.
Diffuse Alveolar Hemorrhage (DAH) is a life-threatening condition characterized by widespread bleeding within the alveoli, often resulting from pulmonary capillaritis, bland pulmonary hemorrhage, or diffuse alveolar damage. It presents with hemoptysis, dyspnea, hypoxemia, and anemia, and can lead to respiratory failure. This case report highlights a rare instance of DAH in a pregnant woman with untreated Graves' disease, emphasizing the importance of considering uncommon etiologies in the absence of typical triggers. A 36-year-old pregnant woman at 37 weeks of gestation presented with hemoptysis and dyspnea. Initial evaluations, including pulmonary CT angiography, ruled out pulmonary embolism but revealed bilateral diffuse alveolar involvement. Bronchoscopy confirmed DAH, with serologic tests indicating hyperthyroidism due to Graves' disease. The patient was treated with pulse methylprednisolone and later methimazole, leading to symptom resolution. She delivered a healthy baby at 40 weeks via uncomplicated vaginal delivery. DAH during pregnancy is rare, and its association with untreated Graves' disease is exceptionally uncommon. In this case, untreated Graves' disease may have contributed to left ventricular diastolic dysfunction, exerting shear stress on pulmonary vasculature and potentially resulting in DAH. The absence of coagulopathy, environmental exposures, or autoantibodies supported this conclusion. This case underscores the need to consider thyroid disorders in the differential diagnosis of bland pulmonary hemorrhage, particularly when other causes are excluded. Early identification and management of underlying causes can significantly improve maternal and fetal outcomes. This report highlights the importance of exploring rare etiologies in cases of DAH, especially in pregnant patients, to ensure timely and effective intervention.
2026-07-10 | Idiopathic Pulmonary Hemosiderosis: A Comprehensive Review of Pathophysiology, Diagnostic Paradigms, and Management Strategies in the Context of Diffuse Alveolar Hemorrhage
Idiopathic pulmonary hemosiderosis (IPH) represents a rare, potentially life-threatening pulmonary syndrome characterized by recurrent episodes of diffuse alveolar hemorrhage (DAH) in the absence of an identifiable underlying etiology. As a diagnosis of strict exclusion within the broader spectrum of DAH, IPH poses substantial diagnostic and therapeutic challenges to clinicians across multiple specialties. This comprehensive review synthesizes current evidence regarding the etiopathogenesis, epidemiology, clinical presentation, diagnostic evaluation, and management of IPH, with particular emphasis on its conceptualization as an immune-mediated disorder and its integration within the contemporary classification of children's interstitial lung disease (chILD). The pathogenesis of IPH remains incompletely elucidated; however, accumulating evidence supports a fundamentally immune-dysregulatory mechanism, with autoantibodies detectable in a significant proportion of patients and well-documented associations with autoimmune conditions, most notably celiac disease, which defines the clinically significant Lane–Hamilton syndrome. The clinical presentation is remarkably heterogeneous, ranging from acute respiratory failure and massive hemoptysis to isolated iron-deficiency anemia without overt pulmonary symptoms, particularly in pediatric populations. Diagnosis requires systematic exclusion of vasculitic, infectious, cardiac, coagulopathic, and toxicologic etiologies through a structured approach encompassing serologic evaluation, bronchoalveolar lavage, high-resolution computed tomography, and, when indicated, lung biopsy demonstrating bland alveolar hemorrhage without capillaritis. Management is predicated upon immunosuppressive therapy, with systemic corticosteroids serving as the cornerstone, augmented by steroid-sparing agents in refractory or relapsing disease, and supplemented by strict gluten-free dietary intervention in patients with coexistent celiac disease. Prognosis has improved substantially in the modern immunosuppressive era, although significant morbidity persists, with relapse rates approaching 60% and progressive pulmonary fibrosis representing a major long-term complication. An interprofessional, collaborative approach involving pulmonology, rheumatology, gastroenterology, and supportive care services is essential to optimize diagnostic accuracy, therapeutic adherence, and longitudinal outcomes in this challenging patient population.
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Drug Discovery Landscape
2 orphan drug designations for Diffuse alveolar hemorrhage.
2 orphan drug designations for Diffuse alveolar hemorrhage.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Recombinant coagulation factor VIIa | proteins | FDA | 2006-04-26 | — | Savara Inc. |
Eptacog alfa (activated) [Newest7] | proteins | EMA | 2005-12-14 | — | [INACTIVE] Savara ApS |
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