ABPA Treatment Guidelines
First-Line Treatment Options
For newly diagnosed acute ABPA, choose either oral prednisolone 0.5 mg/kg/day for 2–4 weeks followed by a gradual taper over 4 months, OR oral itraconazole 400 mg/day (divided twice daily) for 4 months as monotherapy. 1
Prednisolone Monotherapy
- Start prednisolone 0.5 mg/kg/day orally once daily (taken in the morning with food) for 2–4 weeks 1
- Taper using one of two strategies:
- Standard taper (most patients): After initial 2–4 weeks, switch to alternate-day dosing at the same dose for weeks 3–10, then reduce by 5–10 mg every 2 weeks until discontinuation, completing 3–5 months total 1
- Prolonged taper (severe disease/extensive bronchiectasis): Start at 0.75 mg/kg/day for weeks 1–6, reduce to 0.5 mg/kg/day for weeks 7–12, then decrease by 5 mg every 6 weeks for a total course of 6–12 months 1
Itraconazole Monotherapy
- Prescribe itraconazole 400 mg/day (200 mg twice daily with meals) for 4 months 1
- Use conventional capsules taken with meals to improve absorption 1
- Perform therapeutic drug monitoring after 2 weeks; target trough level ≥0.5 mg/L (ideal 1–2 mg/L) 1
- Monitor liver function tests monthly due to hepatotoxicity risk 1
- Maximum dose may be increased to 600 mg/day if needed 1
Critical Drug Interaction Warning
Never combine itraconazole with methylprednisolone—this markedly increases the risk of exogenous Cushing's syndrome and adrenal insufficiency. 1 If combination therapy is required, use prednisolone instead, as itraconazole does not significantly affect prednisolone levels. 1
Do not combine itraconazole with high-dose inhaled corticosteroids (budesonide or fluticasone) due to cytochrome P450 inhibition causing adrenal suppression. 1
When to Use Combination Therapy
Combination therapy (prednisolone + itraconazole) is NOT first-line treatment. 1 Reserve it for patients with:
- ≥2 ABPA exacerbations in the past 1–2 years 1
- Extensive bronchiectasis involving ≥10 lung segments 1
- Blood eosinophil count ≥1000 cells/µL together with extensive bronchiectasis 1
- Steroid-dependent disease (difficulty weaning or relapse upon dose reduction) 1
When initiating itraconazole, a short (<2-week) course of oral glucocorticoids can be added for rapid symptom control, then transition to high-dose inhaled corticosteroids once symptoms improve. 1
Treatment Based on ABPA Classification
Asymptomatic ABPA
- No systemic therapy is indicated 1
- Optimize asthma control with high-dose inhaled corticosteroids 1
- Monitor with clinical review, chest radiograph, and serum total IgE every 3–6 months 1
Serological ABPA Without Bronchiectasis (ABPA-S)
- Treat as standard asthma with high-dose inhaled corticosteroids and bronchodilators 1
- Reserve systemic ABPA-directed therapy for poor asthma control despite optimal management or recurrent exacerbations 1
Acute ABPA With Bronchiectasis or Mucus Plugging
- Systemic treatment (prednisolone or itraconazole) is required even if asymptomatic to prevent progression to irreversible bronchiectasis 1
Monitoring Treatment Response
Assess response at 8–12 weeks using all four criteria: 1
- Clinical improvement ≥50% (symptom score reduction)
- Serum total IgE reduction ≥20% from baseline (≥35% preferred)
- Radiographic resolution of infiltrates
- Spirometric improvement in FEV₁ ≥158 mL (minimal clinically important difference)
After initial assessment, monitor every 3–6 months with: 1
- Clinical review
- Serum total IgE measurement
- Lung function testing
- Chest imaging as clinically indicated
During steroid taper, check serum total IgE every 6–8 weeks: 1
- ≥35% reduction indicates good response 1
- ≥50% rise above stable baseline suggests exacerbation 1
- If IgE plateaus or rises during taper, slow the taper or briefly increase the dose before resuming gradual reduction 1
Managing ABPA Exacerbations
An ABPA exacerbation requires ALL three criteria: 1
- Persistent worsening of respiratory symptoms for ≥2 weeks
- New pulmonary infiltrates on imaging
- Serum total IgE rise ≥50% above the patient's "new baseline" during clinical stability
Distinguish from other exacerbation types: 1
- Asthma exacerbation: No IgE rise, no new infiltrates → treat with short-course oral glucocorticoid
- Bronchiectasis infective exacerbation: No IgE rise, positive sputum cultures → treat with appropriate antibiotics
- ABPA exacerbation: IgE rise ≥50% plus new infiltrates → treat as newly diagnosed acute ABPA with prednisolone or itraconazole monotherapy
For recurrent exacerbations (≥2 in 1–2 years), especially with extensive bronchiectasis, use combination therapy (prednisolone + itraconazole). 1
Approximately 50% of patients experience exacerbations after treatment cessation, requiring retreatment. 1
Second-Line Antifungal Options
Voriconazole, posaconazole, and isavuconazole are NOT first-line agents. 1 Reserve them for patients who cannot receive systemic glucocorticoids or who have intolerance, failure, or resistance to itraconazole. 1
| Antifungal | Recommended Dose | Maximum Dose |
|---|---|---|
| Voriconazole | 400 mg/day (200 mg twice daily) | 600 mg/day |
| Posaconazole | 800 mg/day (oral suspension, divided with meals) OR 300 mg/day (delayed-release tablet once daily) | — |
| Isavuconazole | 200 mg once daily (no food restrictions) | — |
Steroid-Related Monitoring and Prophylaxis
From day 1 of steroid therapy, prescribe: 1
- Calcium 1000–1500 mg/day
- Vitamin D 800–1000 IU/day
Monitor regularly for: 1
- Blood pressure and fasting glucose (hyperglycemia, weight gain, hypertension)
- Cushingoid features, mood changes, gastritis, cataracts, opportunistic infections
Role of Biological Agents
Biological agents (omalizumab, mepolizumab, dupilumab) are NOT first-line therapy. 1 Consider them as steroid-sparing options for treatment-dependent ABPA (patients requiring ongoing therapy after the initial 4-month course or who relapse upon dose reduction). 1
Dosing: 1
- Omalizumab: Dose based on body weight and serum IgE, not exceeding 375 mg subcutaneously twice monthly
- Mepolizumab: 100 mg subcutaneously monthly
- Dupilumab: 600 mg loading dose subcutaneously, then 300 mg every 2 weeks
There is no established fixed duration of dupilumab treatment for ABPA. 1
Definition of Remission
Remission is achieved when the patient remains free of pulmonary infiltrates and eosinophilia for at least 6 months after complete steroid withdrawal. 1, 2
Common Pitfalls to Avoid
- Tapering steroids too quickly leads to relapse: Reduce by 5 mg increments every 2–6 weeks 1
- Ignoring rising IgE trends during taper signals impending exacerbation: Slow or reverse the taper accordingly 1
- Using methylprednisolone with itraconazole precipitates severe Cushing's syndrome: Use prednisolone instead 1
- Neglecting bone protection: Always prescribe calcium and vitamin D at steroid initiation 1
- Using high-dose inhaled corticosteroids alone as primary ABPA therapy: They do not achieve immunological control or reduce exacerbations 1
- Failing to differentiate between asthma, ABPA, and infective bronchiectasis exacerbations: Assess IgE trends, imaging, and sputum cultures 1
- Using nebulized amphotericin B: It has poor efficacy for both acute ABPA and exacerbations and should be avoided 1