Treatment of Diffuse Alveolar Hemorrhage
For diffuse alveolar hemorrhage with hypoxemia, immediately initiate high-dose intravenous glucocorticoids combined with either rituximab (preferred) or cyclophosphamide, and strongly consider adding plasma exchange. 1
Immediate Immunosuppressive Therapy
Glucocorticoid Dosing
- Administer IV methylprednisolone 500-1000 mg/day for 3 consecutive days (maximum cumulative dose of 3 grams) 2, 3
- Transition to weight-based oral prednisone: 1, 2
- <50 kg: 50 mg/day
- 50-75 kg: 60 mg/day
75 kg: 75 mg/day
- Taper gradually to reach 5 mg/day by weeks 19-52 1, 3
Immunosuppressive Agent Selection
- Rituximab is preferred over cyclophosphamide when combined with glucocorticoids for remission induction 2, 3
- Rituximab dosing: 375 mg/m²/week × 4 weeks 1
- Alternative cyclophosphamide dosing if rituximab unavailable: 1
- IV: 15 mg/kg at weeks 0,2,4,7,10,13
- Reduce by 2.5 mg/kg for age >60 years or GFR <30 ml/min/1.73 m²
Plasma Exchange Considerations
Plasma exchange should be considered in DAH with hypoxemia, particularly when: 1
- Serum creatinine >3.4 mg/dL (>300 μmol/L)
- Patient requires dialysis or has rapidly increasing creatinine
- Concomitant anti-glomerular basement membrane disease is present
Evidence Nuances on Plasma Exchange
The PEXIVAS trial did not demonstrate definitive mortality benefit for plasma exchange in DAH, and recent guidelines note increased infection risk without clear mortality benefit in DAH without kidney involvement 1. However, given the high early mortality risk associated with DAH and hypoxemia, plasma exchange remains recommended as part of induction therapy until dedicated trials are conducted 1. The American Society of Apheresis supports this approach 1.
Mechanical Ventilation Management (If Required)
For patients requiring intubation: 2, 3
- Use lung-protective ventilation with tidal volumes 6-8 mL/kg predicted body weight
- Maintain plateau pressure ≤30 cmH₂O
- Apply moderate PEEP (6-8 cmH₂O)
Critical Contraindications
Absolutely avoid chest physiotherapy maneuvers including manual hyperinflation, postural drainage with head-down positioning, percussion, vibratory shaking, or forced expiration techniques, as these can precipitate hemodynamic collapse and extend capillary damage 2, 4
Maintenance Therapy
After achieving remission: 1, 2
- Continue maintenance immunosuppression for 18 months to 4 years to prevent relapse
- Preferred maintenance agents in order:
Adjunctive Therapies
- Avacopan (30 mg twice daily) may be used as an alternative to glucocorticoids in patients at high risk for steroid toxicity, particularly those with GFR <30 ml/min/1.73 m² who may benefit from greater GFR recovery 1, 2
- High-dose intravenous immunoglobulin can be considered in ICU patients with particularly high infection risk 1
Prognostic Factors and Monitoring
High Mortality Risk Factors
DAH occurs in 25% of ANCA-associated vasculitis patients and carries high early mortality when associated with: 1, 2
- Older age
- Severe kidney failure
- Degree of hypoxemia
- Involvement of >50% of lung area at presentation
Monitoring Parameters
Track the following to assess treatment response: 2, 3, 4
- PaO₂/FiO₂ ratio improvement
- Serial chest imaging for resolution of ground-glass opacities and consolidation
- Serial hemoglobin levels
Special Considerations
DAH Without Hypoxemia
In the absence of hypoxemia, DAH has a benign prognosis and responds as extrapulmonary disease is controlled with standard immunosuppression; plasma exchange is not required 1
Refractory Disease
For patients not responding to initial therapy after 4 weeks or showing <50% improvement in disease activity after 6 weeks: 1
- Increase glucocorticoids (IV or oral)
- Switch to rituximab if cyclophosphamide was used initially, or vice versa
- Re-evaluate diagnosis and exclude medication nonadherence, infection, malignancy, or drug-induced vasculitis
- Refer immediately to centers of expertise for confirmation and treatment decisions
Infection Risk Management
Leukopenia should be avoided, with glucocorticoid use minimized in ICU patients receiving assisted ventilation who have particularly high risk of infection and death 1. Infection is the leading cause of death (48%) within the first year in microscopic polyangiitis patients 3