What is the recommended treatment for Allergic Bronchopulmonary Aspergillosis (ABPA)?

Recommended Treatment for 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 use oral itraconazole 400 mg/day (in two divided doses) for 4 months as monotherapy alternatives. 1, 2

First-Line Treatment Options

You have two equally effective first-line choices for acute ABPA:

Option 1: Oral Prednisolone (Preferred for rapid symptom control)

• Start at 0.5 mg/kg/day for 2-4 weeks 1
• Taper gradually over the remaining period to complete a total 4-month course 1, 2
• This low-to-moderate dose protocol results in fewer adverse events compared to high-dose regimens, with similar long-term exacerbation rates 1
• The lower early response rate at 6 weeks is acceptable given the superior safety profile 1

Option 2: Oral Itraconazole (Preferred when steroids contraindicated)

• 400 mg/day in two divided doses for 4 months 3, 2
• Take with meals to enhance absorption 4
• Mandatory therapeutic drug monitoring: target trough level ≥0.5 mg/L 3, 2
• Monthly liver function tests required 3, 2

Treatment Algorithm Based on Clinical Presentation

Asymptomatic ABPA

• Do NOT initiate systemic therapy 3, 2
• Exception: Consider treatment if prolonged mucus plugging is present (risk of irreversible bronchiectasis progression) 1, 2

ABPA-S (Serological ABPA without bronchiectasis)

• Manage as asthma with appropriate asthma medications 3, 2
• Reserve systemic therapy only for poor asthma control or recurrent exacerbations despite optimal asthma management 3, 2

ABPA with Bronchiectasis, Mucus Plugging, or High-Attenuation Mucus

• Requires systemic therapy with either prednisolone OR itraconazole 2

Severe Cases (Blood eosinophils ≥1000 cells/μL AND extensive bronchiectasis ≥10 segments)

• Consider combination therapy with both prednisolone and itraconazole 3, 2
• A short course of glucocorticoids (<2 weeks) may be added initially when starting itraconazole 1, 2

Managing ABPA Exacerbations

ABPA exacerbation is defined as sustained worsening of symptoms ≥2 weeks OR new infiltrates on imaging, with serum total IgE increase ≥50% above baseline 2

• Treat exacerbations identically to newly diagnosed ABPA 3, 2
• For recurrent exacerbations (≥2 in the last 1-2 years), especially with extensive bronchiectasis: use combination therapy with oral prednisolone plus itraconazole 3, 2

Monitoring Treatment Response

Initial Assessment (8-12 weeks)

• Clinical symptom improvement 3, 2
• Serum total IgE should decrease by ≥35% from baseline 3, 2
• Chest radiograph improvement 3, 2

Ongoing Monitoring

• Clinical review, serum total IgE, and lung function tests every 3-6 months 3, 2
• Remission defined as: no pulmonary infiltrates and/or eosinophilia for 6 months after oral steroid withdrawal 2, 4

Critical Drug Interactions and Safety Warnings

Absolute Contraindications

• NEVER combine methylprednisolone with itraconazole - significantly increased risk of exogenous Cushing's syndrome and adrenal insufficiency 1, 2, 4
• AVOID combining high-dose inhaled corticosteroids (budesonide or fluticasone) with itraconazole - can cause exogenous Cushing's syndrome 1, 2

Important Caveats

• High-dose inhaled corticosteroids should NOT be used as primary therapy for acute ABPA 2
• Combination therapy (prednisolone + itraconazole) is NOT recommended as routine first-line treatment 1, 2

Second-Line and Steroid-Dependent ABPA

Alternative Antifungals (when itraconazole fails or is not tolerated)

• Voriconazole, posaconazole, or isavuconazole may be considered 2
• These should NOT be first-line agents 2

Biological Agents (for treatment-dependent ABPA)

• Approximately 10-25% of patients become treatment-dependent 3, 2
• Omalizumab or dupilumab may be considered for steroid-dependent patients who continue symptomatic despite conventional therapy 3, 2
• Biologics are NOT first-line treatments 2

Common Pitfalls to Avoid

• Failing to distinguish ABPA exacerbations from asthma exacerbations or infectious bronchiectasis exacerbations 2
• Using inhaled corticosteroids alone as primary therapy for acute ABPA 2
• Overlooking asymptomatic patients with mucus plugging who may progress to irreversible bronchiectasis 2, 4
• Neglecting therapeutic drug monitoring for itraconazole 3, 2
• Combining contraindicated steroid formulations with itraconazole 1, 2, 4