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

Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)

For acute ABPA, start 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 monotherapy—both are equally effective first-line options. 1

Treatment Algorithm Based on Disease Classification

Asymptomatic ABPA

• Do not initiate systemic therapy 1
• Monitor clinically with serial IgE levels every 3-6 months 1

ABPA-S (Serological ABPA without bronchiectasis)

• Manage as asthma with standard asthma medications (inhaled corticosteroids and bronchodilators) 1
• Reserve systemic therapy only for poor asthma control or recurrent exacerbations despite optimal asthma management 1, 2

Acute ABPA or ABPA with Bronchiectasis (ABPA-B)

This requires systemic treatment with one of two first-line options:

Option 1: Oral Prednisolone Monotherapy

• Start prednisolone 0.5 mg/kg/day for 2-4 weeks 1, 3
• Taper gradually: reduce to alternate-day dosing for 8 weeks, then decrease by 5 mg every 2 weeks 3
• Complete the entire course over 4 months total 1, 3
• Low-dose protocols cause fewer adverse events but may show slower early response 3, 2

Option 2: Oral Itraconazole Monotherapy

• Itraconazole 400 mg/day in two divided doses (200 mg twice daily with meals) for 4 months 1, 2
• Particularly useful when systemic glucocorticoids are contraindicated 1
• Requires therapeutic drug monitoring with target trough level ≥0.5 mg/L 1, 2
• Perform monthly liver function tests 1, 3

ABPA with Mucus Plugging or High-Attenuation Mucus

• Treat as acute ABPA even if asymptomatic, to prevent progression to irreversible bronchiectasis 3, 2

When to Use Combination Therapy

Combination therapy (prednisolone + itraconazole) is NOT recommended as first-line treatment 1, 2, but consider it for:

• Recurrent exacerbations (≥2 in the last 1-2 years) 1, 2
• Extensive bronchiectasis (≥10 segments involved) 1, 2
• Blood eosinophil count ≥1000 cells/μL with extensive bronchiectasis 1, 2
• A short course of glucocorticoids (<2 weeks) may be added initially with itraconazole for symptom control 1, 2

Monitoring Treatment Response

Assess response at 8-12 weeks using three parameters 1, 2:

• Clinical symptoms (improved asthma control, reduced sputum production)
• Serum total IgE (should decrease by ≥35% from baseline) 1
• Chest radiographs (resolution of infiltrates)

Ongoing monitoring every 3-6 months 1, 2:

• Clinical review
• Serum total IgE levels
• Pulmonary function tests

Remission is defined as absence of pulmonary infiltrates and/or eosinophilia for 6 months after oral steroid withdrawal 3, 2

Management of ABPA Exacerbations

ABPA exacerbation criteria 2:

• Sustained worsening of clinical symptoms (≥2 weeks)
• New infiltrates on chest imaging
• Increase in serum total IgE by ≥50% above baseline

Treatment approach:

• Treat exacerbations the same as newly diagnosed ABPA 1, 2
• For recurrent exacerbations, use combination therapy (prednisolone + itraconazole) 1, 2

Critical Drug Interactions and Pitfalls to Avoid

Never combine methylprednisolone with itraconazole—this significantly increases the risk of Cushing's syndrome and adrenal insufficiency 1, 3, 2

Avoid high-dose inhaled corticosteroids (budesonide or fluticasone) with itraconazole—this can cause exogenous Cushing's syndrome 3, 2

High-dose inhaled corticosteroids should not be used as primary therapy for acute ABPA—they are insufficient for systemic disease control 2

Second-Line and Steroid-Sparing Options

Alternative Antifungals

• Voriconazole, posaconazole, and isavuconazole are NOT first-line agents 2
• Consider only if contraindications to glucocorticoids exist AND there is intolerance, failure, or resistance to itraconazole 3, 2

Biological Agents for Treatment-Dependent ABPA

Approximately 10-25% of ABPA patients become treatment-dependent, requiring ongoing therapy 1, 2

Omalizumab (anti-IgE antibody):

• Consider for treatment-dependent ABPA (patients with persistent symptoms despite conventional therapy) 1
• Not restricted by total IgE level limitations 4

Dupilumab (anti-IL-4/IL-13):

• Recommended for treatment-dependent ABPA 1
• No established fixed duration of treatment 1
• Good response indicated by major symptom improvement, chest radiograph improvement, and ≥20% reduction in serum total IgE 1

Mepolizumab (anti-IL-5):

• May improve FEV1, radiological findings, and quality of life 4
• Useful as glucocorticoid-sparing agent 4

Biological agents are NOT first-line therapy but serve as options for steroid-dependent patients who cannot tolerate or require excessive doses of conventional therapy 1, 2