Raghu G, Remy-Jardin M, Myers JL, et al; American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Sep 1;198(5):e44-e68. doi: 10.1164/rccm.201807-1255ST. PubMed PMID: 30168753.
Lynch DA, Sverzellati N, Travis WD, et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir Med. 2018 Feb;6(2):138-153. doi: 10.1016/S2213-2600(17)30433-2. Epub 2017 Nov 15. Review. PubMed PMID: 29154106.
Travis WD, Costabel U, Hansell DM, et al; ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013 Sep 15;188(6):733-48. doi: 10.1164/rccm.201308-1483ST. PubMed PMID: 24032382.
Definition, Etiology, PathogenesisTop
Diffuse alveolar hemorrhage (DAH) refers to the extravasation of blood from pulmonary capillaries with accumulation of erythrocytes in the alveolar spaces. There is no consensus classification for DAH. The underlying cause of DAH is generally reflected in the histopathologic pattern. One of 3 patterns may be observed:
1) Pulmonary capillaritis: Neutrophilic inflammation of the alveolar interstitium leads to vascular injury or necrosis and subsequent loss of the structural integrity of alveolar epithelial or capillary endothelial cells. Causes of pulmonary capillaritis include systemic vasculitides (granulomatosis with polyangiitis and microscopic polyangiitis), anti-glomerular basement membrane [GBM] disease, rheumatic diseases (systemic lupus erythematosus [SLE], rheumatoid arthritis, mixed connective tissue disease, primary antiphospholipid syndrome), and drug reactions.
2) Bland pulmonary hemorrhage: This is characterized by hemorrhage into the alveolar space with no inflammation or destruction of the alveolar structures. Causes include anticoagulant therapy, thrombocytopenia, idiopathic pulmonary hemosiderosis, and mitral stenosis.
3) Diffuse alveolar damage: Edema of the alveolar walls with hyaline membranes. Causes include any infection causing acute respiratory distress syndrome, connective tissue diseases (polymyositis and SLE), drugs (amiodarone, amphetamine, nitrofurantoin, cocaine), acute interstitial pneumonia, radiation therapy, and pulmonary infarction.
Clinical Features and Natural HistoryTop
Symptoms include dyspnea, cough, hemoptysis (an absent or late clinical finding in up to 33% of cases), or disease-specific complaints. DAH due to immunologic causes is usually preceded by a prodromal phase lasting >10 days, with symptoms including malaise, arthralgia, or manifestations of a preexisting immunologic disorder.
1. Chest radiography usually reveals patchy or disseminated opacities, which may follow a relapse-remitting or migratory pattern.
2. High-resolution computed tomography (HRCT) reveals ground-glass opacities or consolidations that reflect blood filling the alveoli. In patients with recurrent DAH, reticulation may appear, providing evidence of interstitial fibrosis.
3. Laboratory tests: Iron deficiency anemia is commonly encountered in chronic recurrent hemorrhage. Thrombocytopenia should be excluded. An underlying bleeding diathesis should be assessed with an evaluation of coagulation. Serum creatinine, urinalysis, and urine microscopy are of value, as the presence of renal dysfunction, hematuria, red blood cell (RBC) casts, or proteinuria is suggestive of a systemic vasculitis. A urine drug screen test may reveal evidence of culprit illicit drug use. Evaluation of specific autoantibodies, including antineutrophil cytoplasmic antibodies, anti-GBM antibodies, antinuclear antibodies, and extractable nuclear antigens may permit the diagnosis of an underlying systemic inflammatory process.
4. Pulmonary function tests: A transient increase in carbon dioxide diffusing capacity of the lungs (DLCO) is a characteristic feature of DAH. Recurrent DAH is associated with a restrictive pattern and reduced DLCO.
5. Bronchoscopy with bronchoalveolar lavage (BAL) is essential to the accurate identification of DAH. An increasing RBC presence on sequential samples is consistent with the diagnosis. Evidence of hemorrhage should ideally be confirmed in more than one bronchial segment. The presence of hemosiderin-laden macrophages provides evidence of chronic hemorrhage even when frank (clinically evident) bleeding is not apparent at the time of bronchoscopy. BAL also serves to exclude other causes of diffuse pulmonary infiltrates or hemoptysis.
In severely ill patients with a suspected immunologic cause of DAH, promptly start high-dose IV glucocorticoid treatment (eg, methylprednisolone 500-1000 mg/d) for 3 days. Cytotoxic therapies including cyclophosphamide or rituximab should be considered in the setting of an underlying capillaritis (see Vasculitis Syndromes). In the case of bleeding, coagulopathy, or thrombocytopenia, administer blood products and reversal agents as required. Attempt to achieve adequate oxygen saturation by administering oxygen or using assisted ventilation when necessary. Treat respiratory insufficiency (see Acute Respiratory Failure) and pulmonary hemorrhage (rare; see Hemoptysis).