Treatment of Vasculitis with Diffuse Alveolar Hemorrhage
Immediately initiate high-dose intravenous methylprednisolone (500-1000 mg/day for 3 consecutive days, maximum 3 grams cumulative) combined with either rituximab or cyclophosphamide, and strongly consider adding plasma exchange for patients with hypoxemia. 1, 2
Initial Immunosuppressive Therapy
Glucocorticoid Protocol
- Administer IV methylprednisolone 500-1000 mg/day for 3 consecutive days (maximum cumulative dose of 3 grams) for severe diffuse alveolar hemorrhage with hypoxemia 1, 2
- Transition to weight-based oral prednisone after pulse therapy: 1, 2
- Body weight <50 kg: 50 mg/day
- Body weight 50-75 kg: 60 mg/day
- Body weight >75 kg: 75 mg/day
- Taper gradually to reach 5 mg/day by weeks 19-52 2
Immunosuppressive Agent Selection
- Rituximab is preferred over cyclophosphamide when combined with glucocorticoids for remission induction 1, 2
- Rituximab dosing: 375 mg/m²/week for 4 weeks 2
- Alternative cyclophosphamide if rituximab unavailable: 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) 2
- The combination of cyclophosphamide and corticosteroids represents the standard initial treatment for ANCA vasculitis 3
Plasma Exchange Indications
Add plasma exchange for diffuse alveolar hemorrhage with hypoxemia, particularly when: 3, 2
- Serum creatinine >300-500 μmol/L (>3.4-5.7 mg/dL)
- Patient requires dialysis or has rapidly increasing serum creatinine
- Concomitant anti-glomerular basement membrane disease is present
Plasma Exchange Protocol
- Perform 7-10 treatments over 14 days with 60 ml/kg volume replacement 3
- Administer daily until bleeding stops, then every other day 3
- Total of 7-10 treatments for diffuse alveolar hemorrhage 3
Evidence Nuances on Plasma Exchange
The PEXIVAS trial (the largest and most recent high-quality study) enrolled 191 patients with diffuse alveolar hemorrhage (61 with severe hypoxemia, including 29 mechanically ventilated) and found no definitive mortality benefit from plasma exchange 1, 4. Among those with diffuse alveolar hemorrhage, 8/95 (8.4%) receiving plasma exchange died within 1 year versus 15/96 (15.6%) without plasma exchange (hazard ratio 0.52; CI 0.21-1.24), but this did not reach statistical significance 4. However, guidelines continue to recommend considering plasma exchange because the mortality reduction trend, combined with low risk and high clinical stakes, favors intervention 3, 1. The 2024 KDIGO guidelines note that plasma exchange can be considered for more severe presentations, especially if oliguric 3.
Mechanical Ventilation Management (If Required)
- Use lung-protective ventilation strategies with tidal volumes 6-8 mL/kg predicted body weight 1, 2
- Maintain plateau pressure ≤30 cmH₂O 1, 2
- Apply moderate PEEP (6-8 cmH₂O) to maintain oxygenation 2
Critical Contraindications
Do not perform 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 1, 5
Maintenance Therapy
- Continue maintenance immunosuppression for 18 months to 4 years after achieving remission to prevent relapse 1, 2
- Preferred maintenance agents include rituximab, azathioprine (1-2 mg/kg/day), or mycophenolate mofetil (up to 1 g twice daily) 3, 2
- Maintenance therapy should be continued for at least 18-24 months in patients who remain in complete remission 3
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 5, 2
- High-dose intravenous immunoglobulin can be considered in ICU patients with particularly high infection risk 2
Monitoring Parameters
Track the following to assess treatment response: 1, 2
- PaO₂/FiO₂ ratio improvement
- Serial chest imaging for resolution of ground-glass opacities and consolidation
- Serial hemoglobin levels
- Oxygenation parameters
Prognostic Factors
Diffuse alveolar hemorrhage occurs in approximately 25% of ANCA-associated vasculitis patients and carries high early mortality risk 1, 6. Mortality risk factors include: 5, 6
- Older age
- Severe kidney failure
- Degree of hypoxemia (mortality rises to 50% for cases requiring mechanical ventilation)
- Involvement of >50% of lung area at presentation
Mortality risk correlates more with the rate of hemoptysis rather than quantity 1, 5
Special Considerations
- In the absence of hypoxemia, diffuse alveolar hemorrhage has a more benign prognosis and responds as the underlying disease is controlled with standard immunosuppression; plasma exchange is not required 5, 2
- For patients not responding to initial therapy within 48-72 hours, switch between rituximab and cyclophosphamide, and re-evaluate diagnosis to exclude infection, malignancy, or drug-induced vasculitis 5, 2
- Delayed treatment dramatically worsens outcomes—begin empiric immunosuppressive therapy immediately when immune-mediated diffuse alveolar hemorrhage is suspected, even before bronchoscopy confirmation 1, 5
- Sepsis and cardiovascular/thromboembolic events are important early complications requiring vigilant monitoring 6
- Patients with refractory disease should be referred immediately to centers with expertise in vasculitis management 3, 1, 5