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

Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)

For acute ABPA, the first-line treatment options are either oral prednisolone (0.5 mg/kg/day for 2-4 weeks, tapered and completed over 4 months) or oral itraconazole (400 mg/day in two divided doses) for 4 months. 1, 2

Treatment Based on ABPA Classification

• Asymptomatic ABPA: Systemic therapy is not recommended 1, 2
• ABPA-S (Serological ABPA without bronchiectasis): Manage like asthma with appropriate asthma medications; use systemic therapy only if there is poor asthma control or recurrent exacerbations despite optimal asthma management 1, 2
• ABPA with bronchiectasis (ABPA-B): Requires systemic therapy with either oral prednisolone or itraconazole 1
• ABPA with mucus plugging (ABPA-MP) or high-attenuation mucus (ABPA-HAM): Requires systemic therapy as for acute ABPA 1

First-Line Treatment Options for Acute ABPA

Oral Glucocorticoids

• Prednisolone 0.5 mg/kg/day for 2-4 weeks, then tapered and completed over 4 months 1, 3
• Standard tapering protocol: After initial 2-4 weeks at full dose, taper to alternate-day dosing for 8 weeks, then reduce by 5 mg every 2 weeks until discontinuation 3, 4
• Low-dose protocols result in fewer adverse events but may have lower early response rates 1, 3

Oral Antifungals

• Itraconazole 400 mg/day in two divided doses for 4 months 1, 2
• Therapeutic drug monitoring recommended (target trough level ≥0.5 mg/L) 2, 3
• Monthly liver function tests should be performed 2, 3
• Preferred option when systemic glucocorticoids are contraindicated 1

Important Considerations

• Combination of itraconazole and glucocorticoids is not recommended as first-line therapy, but a short course of glucocorticoids (<2 weeks) may be used initially with oral itraconazole 1
• Methylprednisolone should not be used with itraconazole due to higher risk of Cushing's syndrome and adrenal insufficiency 1, 3
• High-dose inhaled corticosteroids (ICS) should not be used as primary therapy for acute ABPA 1
• Patients with blood eosinophil count ≥1000 cells/μL and extensive bronchiectasis (≥10 segments) may benefit from combination therapy 1, 2

Management of ABPA Exacerbations

• ABPA exacerbations are characterized by sustained worsening (≥2 weeks) of clinical symptoms or new infiltrates on chest imaging, with an increase in serum total IgE by ≥50% above baseline 1
• Treat ABPA exacerbations the same way as newly diagnosed ABPA 1, 2
• Consider combination of oral prednisolone and itraconazole for recurrent exacerbations (≥2 in the last 1-2 years), especially in patients with extensive bronchiectasis 1, 2

Monitoring Treatment Response

• Assess response after 8-12 weeks using clinical symptoms, serum total IgE levels (should decrease by ≥35% from baseline), and chest radiographs 2
• Continue monitoring with clinical review, serum total IgE levels, and lung function tests every 3-6 months 2, 4
• Patients are considered in remission when they remain without pulmonary infiltrates and/or eosinophilia for 6 months after oral steroid withdrawal 3

Second-Line and Alternative Therapies

• Voriconazole, posaconazole, and isavuconazole should not be used as first-line agents but may be considered if there are contraindications to systemic glucocorticoids and intolerance, failure, or resistance to itraconazole therapy 1, 3
• Biological agents (including omalizumab and dupilumab) are not recommended as first-line therapy but may be options for steroid-dependent patients 1, 2
• Approximately 10-25% of ABPA patients become treatment-dependent, requiring ongoing therapy 2

Common Pitfalls to Avoid

• Failing to distinguish between asthma exacerbations, ABPA exacerbations, and infective exacerbations of bronchiectasis 1
• Using high-dose inhaled corticosteroids alone as primary therapy for acute ABPA 1, 5
• Combining inhaled budesonide or fluticasone with itraconazole, which can cause exogenous Cushing's syndrome 1
• Using methylprednisolone with itraconazole due to higher risk of Cushing's syndrome 1, 3
• Overlooking the need to treat asymptomatic patients with prolonged mucus plugging to prevent progression to irreversible bronchiectasis 3