Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)
For acute ABPA, initiate treatment with either oral prednisolone 0.5 mg/kg/day for 2-4 weeks (then tapered over 4 months) or oral itraconazole 400 mg/day for 4 months as first-line monotherapy. 1, 2
Treatment Algorithm Based on Disease Classification
Asymptomatic ABPA
- Do not initiate systemic therapy for asymptomatic patients without evidence of active disease 2, 3
- Monitor with clinical assessment and serum IgE levels every 3-6 months 2
ABPA-S (Serological ABPA without bronchiectasis)
- Manage primarily as asthma with inhaled corticosteroids and long-acting β2-agonists 2, 3
- Reserve systemic therapy only for poor asthma control or recurrent exacerbations despite optimal asthma management 2, 3
Acute ABPA (including ABPA-B, ABPA-MP, ABPA-HAM)
Choose one of two first-line options:
Option 1: Oral Prednisolone
- Start at 0.5 mg/kg/day for 2-4 weeks 1, 2
- Taper and complete over 4 months total duration 1, 2
- This low-to-moderate dose protocol results in fewer adverse events compared to higher doses, with similar exacerbation rates 1
- Critical warning: Never use methylprednisolone with itraconazole due to significantly increased risk of Cushing's syndrome and adrenal insufficiency 1, 2
Option 2: Oral Itraconazole
- Dose: 400 mg/day in two divided doses for 4 months 2, 3
- Mandatory therapeutic drug monitoring: Target trough level ≥0.5 mg/L 2
- Mandatory monthly liver function tests throughout treatment 2
- Preferred when systemic glucocorticoids are contraindicated 2, 3
Combination Therapy Considerations
- Do not use combination therapy as first-line treatment 2, 3
- A short course of glucocorticoids (<2 weeks) may be added initially with itraconazole for symptom control 1, 2
- Consider combination therapy for patients with blood eosinophil count ≥1000 cells/μL and extensive bronchiectasis (≥10 segments) 2
Management of ABPA Exacerbations
Defining an Exacerbation
- Sustained worsening of clinical symptoms for ≥2 weeks OR new infiltrates on chest imaging 2
- Plus serum total IgE increase ≥50% above baseline 2
Treatment Approach
- Treat exacerbations identically to newly diagnosed acute ABPA with either prednisolone or itraconazole 2, 3
- For recurrent exacerbations (≥2 in the last 1-2 years): Use combination of oral prednisolone and itraconazole, especially with extensive bronchiectasis 2, 3
Monitoring Treatment Response
Initial Assessment (8-12 weeks)
- Clinical symptom improvement 2, 3
- Serum total IgE should decrease by ≥35% from baseline 2, 3
- Chest radiograph improvement 2, 3
Long-term Monitoring
- Clinical review, serum total IgE levels, and lung function tests every 3-6 months 2, 3
- Remission criteria: No pulmonary infiltrates and/or eosinophilia for 6 months after oral steroid withdrawal 2
Treatment-Dependent ABPA (10-25% of patients)
Second-Line Antifungals
- Voriconazole, posaconazole, or isavuconazole may be considered if contraindications to glucocorticoids exist AND there is intolerance, failure, or resistance to itraconazole 2
- These are not first-line agents 2
Biological Agents
- Consider omalizumab or dupilumab for steroid-dependent patients requiring ongoing therapy 2, 3
- Not recommended as first-line therapy 2
- No established fixed duration for dupilumab treatment; monitor for major symptom improvement, chest radiograph improvement, and ≥20% reduction in serum total IgE 3
Critical Pitfalls to Avoid
- Never use high-dose inhaled corticosteroids alone as primary therapy for acute ABPA 2
- Never combine inhaled budesonide or fluticasone with itraconazole due to risk of exogenous Cushing's syndrome 1, 2
- Never use methylprednisolone with itraconazole due to higher risk of Cushing's syndrome and adrenal insufficiency 1, 2
- Distinguish ABPA exacerbations from asthma exacerbations and infective bronchiectasis exacerbations before initiating treatment 2
- Treat asymptomatic patients with prolonged mucus plugging to prevent progression to irreversible bronchiectasis 2