Management of Diffuse Alveolar Hemorrhage
The treatment of diffuse alveolar hemorrhage (DAH) should be initiated without delay, even before confirming the diagnosis, with a combination of high-dose glucocorticoids, cyclophosphamide or rituximab, and consideration of plasmapheresis in cases with hypoxemia to reduce mortality. 1
Initial Assessment and Diagnosis
Determine the underlying cause of DAH, including:
- ANCA-associated vasculitis (most common cause, ~74%)
- Systemic lupus erythematosus
- Goodpasture syndrome (anti-GBM disease)
- Infectious causes
- Drug-induced or toxic exposures
- Post-transplantation complications
Clinical presentation:
- Hemoptysis (present in ~77% of cases)
- Drop in hemoglobin (1.0-3.0 g/dL)
- Hypoxemia
- Diffuse alveolar infiltrates on imaging
Diagnostic confirmation:
- Bronchoscopy with bronchoalveolar lavage (BAL)
- Macroscopically bloody fluid (in ~44% of cases)
- Siderophagic alveolitis on BAL cytology
- HRCT imaging to identify appropriate areas for BAL 2
- Bronchoscopy with bronchoalveolar lavage (BAL)
Treatment Algorithm
1. Immunosuppressive Therapy
First-line treatment:
- High-dose glucocorticoids: Methylprednisolone 500-1000 mg/day IV for 3 days, followed by oral prednisone 1
- PLUS one of the following:
- Cyclophosphamide: Oral (2 mg/kg/day for 3-6 months) or IV (15 mg/kg at weeks 0,2,4,7,10,13)
- Rituximab: 375 mg/m²/week for 4 weeks
Dose adjustments for cyclophosphamide:
- Age >60 years: Reduce dose by 25%
- Age >70 years: Reduce dose by 50%
- GFR <30 ml/min/1.73 m²: Reduce dose 1
2. Plasmapheresis
Indications:
- DAH with hypoxemia (oxygen saturation ≤85% on room air)
- Anti-GBM disease (Goodpasture syndrome)
- Patients requiring mechanical ventilation
Regimen: 7 sessions over 14 days 1
Evidence: PEXIVAS trial showed a trend toward reduced mortality in DAH patients receiving plasma exchange (8.4%) compared to those without (15.6%), though not statistically significant 3
3. Supportive Care
- Oxygen therapy and mechanical ventilation as needed
- Correction of anemia with blood transfusions
- Prevention of opportunistic infections
- Avoid leukopenia in critically ill patients
- Minimize glucocorticoid exposure in ICU patients to reduce infection risk 1
Maintenance Therapy
After achieving remission, continue maintenance therapy for 18 months to 4 years:
- Options include:
- Rituximab: Either 500 mg at remission and months 6,12,18 or 1000 mg at remission and months 4,8,12,16
- Azathioprine: 1.5-2 mg/kg/day for 18-24 months, then 1 mg/kg/day until 4 years after diagnosis
- Low-dose glucocorticoids: 5-7.5 mg/day for 2 years, then taper by 1 mg every 2 months 1
Monitoring
- Complete blood count, renal function, urinalysis at each visit
- Monitor for treatment toxicity and disease activity
- Regular pulmonary function tests and imaging to detect recurrence 1
Prognostic Factors and Outcomes
Poor prognostic factors include:
- Need for dialysis (mortality 50% vs 15.4% without dialysis)
- Oxygen saturation <90% at admission (mortality 50% vs 5.3%)
- Requirement for mechanical ventilation (mortality 76.9% vs 6.8%) 4
Common Pitfalls to Avoid
- Delayed diagnosis
- Inadequate immunosuppression
- Missing concurrent infections
- Overreliance on ANCA titers
- Premature discontinuation of therapy 1
- Failure to recognize DAH in patients without hemoptysis
- Failure to perform early bronchoscopy to confirm diagnosis and exclude infection 4
Special Considerations
- For infectious causes of DAH in immunocompetent patients (influenza A, dengue, leptospirosis, malaria, S. aureus), antimicrobial therapy should be directed at the specific pathogen 5
- In hematopoietic cell transplant recipients, DAH often occurs in the first few weeks post-transplant and may require different management approaches 6
- Avoid methotrexate in patients with GFR <60 ml/min/1.73 m² 1
- Check immunoglobulin levels before using IVIG, as patients with selective IgA deficiency may develop anaphylactic reactions 1