What is the treatment for Diffuse Alveolar Hemorrhage (DAH)?

Treatment of Diffuse Alveolar Hemorrhage (DAH)

Immediately initiate high-dose intravenous glucocorticoids (methylprednisolone 500-1000 mg/day for 3 days, maximum 3 grams cumulative) combined with either rituximab (preferred) or cyclophosphamide for immune-mediated DAH, as this represents the standard of care for patients with DAH and hypoxemia. 1

Initial Management and Diagnosis

• Establish the diagnosis through bronchoalveolar lavage showing increasingly bloody returns in sequential aliquots 1
• Recognize that hemoptysis may be absent in up to 50% of cases, so do not wait for this sign to initiate treatment 2
• Begin empiric immunosuppressive therapy immediately when immune-mediated DAH is suspected (ANCA-associated vasculitis, anti-GBM disease, connective tissue disease) rather than delaying for bronchoscopy confirmation, as delayed treatment dramatically worsens outcomes 1

Glucocorticoid Dosing Protocol

For severe DAH with hypoxemia, administer intravenous methylprednisolone 500-1000 mg/day for 3 consecutive days (maximum cumulative dose of 3 grams). 1

After pulse therapy, transition to weight-based oral prednisone: 1

• <50 kg: 50 mg/day
• 50-75 kg: 60 mg/day
• >75 kg: 75 mg/day

Taper to reach 5 mg/day by weeks 19-52 1

Immunosuppressive Therapy Selection

Choose rituximab over cyclophosphamide as the preferred agent when combined with glucocorticoids for remission induction. 1

• Both rituximab and cyclophosphamide are effective, but rituximab is conditionally preferred based on current guidelines 1
• Continue maintenance immunosuppression for 18 months to 4 years after remission to prevent relapse in ANCA-associated vasculitis 1

Plasma Exchange Considerations

Consider plasma exchange for DAH with hypoxemia, particularly when serum creatinine >300 μmol/L (>3.4 mg/dL), requiring dialysis, or with concomitant anti-GBM disease. 1

Evidence Nuances on Plasma Exchange:

The 2024 EULAR guidelines reveal important limitations: 3

• No clinically relevant benefit of plasma exchange was demonstrated for DAH mortality in the PEXIVAS trial (191 patients with DAH, 61 with hypoxemia) 3
• The substudy was underpowered for mortality endpoints 3
• Insufficient evidence exists to make a recommendation for or against plasma exchange in isolated DAH 3
• The primary driver for plasma exchange in DAH patients is usually the degree of associated renal impairment rather than the pulmonary hemorrhage itself 3

However, for anti-GBM disease with DAH, aggressive early immunosuppression with cyclophosphamide, glucocorticoids, AND plasmapheresis substantially improves outcomes—delayed treatment results in 96% mortality. 1

Ventilator Management for Severe Cases

Use lung-protective ventilation strategies: 1

• Tidal volumes: 6-8 mL/kg predicted body weight
• Plateau pressure: ≤30 cmH₂O
• PEEP: Moderate levels (6-8 cmH₂O) to maintain oxygenation
• Avoid aggressive recruitment maneuvers as high pressures can worsen bleeding 1

Critical Contraindications in DAH

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

• Manual hyperinflation causes large intrathoracic pressure fluctuations that decrease cardiac output and extend capillary damage 1
• Head-down positioning increases pulmonary blood flow to damaged areas 1
• Percussion causes direct mechanical trauma to hemorrhaging tissue 1

Etiology-Specific Considerations

ANCA-Associated Vasculitis (AAV):

• DAH occurs in approximately 25% of AAV patients 1
• Mortality risk factors include older age, severe kidney failure, degree of hypoxemia, and >50% lung area involvement 1
• Infection is the leading cause of death (48%) within the first year, so balance aggressive immunosuppression against infection risk 1

Anti-GBM Disease:

• Requires the most aggressive approach with cyclophosphamide, glucocorticoids, AND plasmapheresis 1
• Patients presenting on dialysis have 35% mortality and >90% remain dialysis-dependent at 1 year 1
• Even dialysis-dependent patients with acute presentation and favorable biopsy features may benefit from treatment 1

DAH Without Hypoxemia:

• Generally has more benign prognosis and responds as the underlying disease is controlled 1
• Standard immunosuppression without plasma exchange is typically sufficient 1

Adjunctive Therapies

• Avacopan may be considered as adjunctive therapy to reduce glucocorticoid exposure in patients at high risk for steroid toxicity 1
• Platelet transfusions should be administered in thrombocytopenic patients 4, 2
• Antifibrinolytic drugs and topical procoagulant factors may be used in select cases 4

Monitoring Parameters

Track the following to assess treatment response: 1

• Clinical symptoms (dyspnea, hemoptysis)
• Oxygenation parameters (PaO₂/FiO₂ ratio improvement)
• Chest imaging for resolution of ground-glass opacities and consolidation
• Serial hemoglobin levels

Infectious DAH

If infectious etiology is suspected (influenza, dengue, leptospirosis, malaria, Staphylococcus aureus), initiate broad-spectrum antibiotics with β-lactam plus macrolide or respiratory fluoroquinolone, with MRSA coverage in high-risk patients. 5, 6

• For severe community-acquired pneumonia with DAH: ceftriaxone 2g IV daily or cefotaxime 2g IV q8h plus clarithromycin 5
• For hospital-acquired pneumonia: dual antipseudomonal coverage with piperacillin-tazobactam, cefepime, or meropenem plus levofloxacin or ciprofloxacin 5
• Add vancomycin or linezolid for MRSA coverage if prior IV antibiotics within 90 days or unit MRSA prevalence >20% 5

Refractory Disease Management

For patients not responding to standard therapy, refer immediately to a center with expertise in vasculitis. 3, 1

• Reassess diagnosis and exclude infection or alternative diagnoses 3
• Consider combination rituximab plus cyclophosphamide for truly refractory organ-threatening disease 3
• Intravenous immunoglobulins may be added for persistent manifestations, particularly in patients at high infection risk 3

Prognosis

• DAH with hypoxemia carries high early mortality risk requiring prompt intervention 1
• Overall in-hospital mortality exceeds 20% 2
• Mortality risk correlates more with the rate of hemoptysis rather than quantity 1
• For transplant candidates with history of AAV and DAH, delay transplantation until complete clinical remission for ≥6 months 1