Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)
For acute ABPA, initiate treatment with oral prednisolone 0.5 mg/kg/day for 2-4 weeks, then taper over a total 4-month course, OR oral itraconazole 400 mg/day (in two divided doses) for 4 months as monotherapy. 1
Initial Treatment Selection Algorithm
First-Line Monotherapy Options
Prednisolone regimen: 1
- Start at 0.5 mg/kg/day for 2-4 weeks
- Taper gradually over remaining period to complete 4 months total
- Monitor serum total IgE every 6-8 weeks as disease activity marker
Itraconazole regimen: 1
- 400 mg/day in two divided doses with meals for 4 months
- Requires therapeutic drug monitoring (target trough level ≥0.5 mg/L)
- Perform monthly liver function tests
- Preferred when systemic glucocorticoids are contraindicated
Critical Drug Interaction Warning
Never combine methylprednisolone with itraconazole - this combination carries significantly higher risk of exogenous Cushing's syndrome and adrenal insufficiency. 1 Similarly, avoid combining high-dose inhaled corticosteroids (budesonide or fluticasone) with itraconazole due to cytochrome P450 inhibition leading to adrenal suppression. 1, 2
When to Use Combination Therapy
Do NOT use combination therapy as first-line treatment. 1 However, consider combining prednisolone plus itraconazole in these specific scenarios: 1
- Recurrent exacerbations (≥2 in the last 1-2 years)
- Extensive bronchiectasis (≥10 segments involved)
- Blood eosinophil count ≥1000 cells/μL with extensive bronchiectasis
A short course of glucocorticoids (<2 weeks) may be added initially when starting itraconazole to rapidly control symptoms, then transition to high-dose inhaled corticosteroids once symptoms improve. 1
Treatment Based on ABPA Classification
Asymptomatic ABPA
Do not treat with systemic therapy. 1, 3 Instead, optimize asthma management with high-dose inhaled corticosteroids and monitor closely with clinical review, chest radiograph, and serum total IgE every 3-6 months. 1, 3
ABPA-S (Serological ABPA without bronchiectasis)
Manage like asthma with standard asthma medications. 1, 3 Only initiate systemic ABPA-specific therapy if: 1
- Poor asthma control despite optimal asthma management, OR
- Recurrent exacerbations despite appropriate asthma therapy
Acute ABPA with Bronchiectasis or Mucus Plugging
Requires systemic treatment even if asymptomatic, as prolonged mucus plugging can progress to irreversible bronchiectasis. 1, 4 Use either prednisolone or itraconazole regimen as outlined above.
Managing ABPA Exacerbations
Defining an Exacerbation
ABPA exacerbation requires ALL of the following: 1
- Sustained worsening of respiratory symptoms (≥2 weeks duration)
- New infiltrates on chest imaging
- Serum total IgE increase ≥50% above the "new baseline" (during clinical stability)
Distinguish from asthma exacerbations (no IgE rise, no new infiltrates) and bronchiectasis infective exacerbations (no IgE rise, positive sputum cultures). 1
Treatment Approach
Treat ABPA exacerbations identically to newly diagnosed ABPA - use either prednisolone or itraconazole monotherapy. 1 For recurrent exacerbations (≥2 in 1-2 years), especially with extensive bronchiectasis, use combination therapy with both prednisolone and itraconazole. 1
Second-Line Antifungal Options
Voriconazole, posaconazole, and isavuconazole should NOT be used as first-line agents. 1 Reserve these for: 1, 5, 6
- Contraindications to systemic glucocorticoids AND
- Intolerance, failure, or resistance to itraconazole
When using second-line azoles, 70-80% of patients who tolerate voriconazole or posaconazole demonstrate clinical response. 5
Monitoring Treatment Response
Assessment Timeline
Evaluate response at 8-12 weeks after treatment initiation using: 1, 3
- Clinical symptoms (use Likert scale: ≥50% improvement = good response)
- Serum total IgE (≥20% reduction from baseline = good response, though ≥35% is preferred)
- Chest radiographs (assess for resolution of infiltrates)
- Spirometry (MCID for FEV1 = 158 mL improvement)
Ongoing Monitoring
Continue monitoring every 3-6 months with: 3, 7
- Clinical review
- Serum total IgE levels
- Lung function tests
- Chest radiographs as clinically indicated
Treatment-Dependent ABPA
Approximately 10-25% of patients become treatment-dependent, requiring ongoing therapy to maintain control. 3, 7 For these patients, consider: 7
- Long-term itraconazole maintenance
- Biological agents (omalizumab or dupilumab)
- Low-dose maintenance glucocorticoids (least preferred due to toxicity)
Biological agents are NOT first-line therapy but serve as steroid-sparing options in treatment-dependent or frequently exacerbating patients. 1, 7
Therapies to Avoid
High-dose inhaled corticosteroids alone do not achieve immunological control or reduce exacerbations when used as primary ABPA therapy. 1
Nebulized amphotericin B has poor efficacy for both acute ABPA and ABPA exacerbations. 1
Defining Remission
Remission = absence of pulmonary infiltrates and/or eosinophilia for 6 months after oral steroid withdrawal. 4 However, nearly 50% of patients experience exacerbations after treatment cessation, requiring retreatment. 1