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

Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)

For acute ABPA, initiate treatment with oral prednisolone 0.5 mg/kg/day for 2-4 weeks, tapered over 4 months, or oral itraconazole 400 mg/day for 4 months as first-line monotherapy options. 1, 2, 3

Treatment Algorithm Based on Disease Classification

Asymptomatic ABPA

• Do not initiate systemic therapy for asymptomatic patients without evidence of bronchiectasis or mucus plugging 2, 3
• Optimize asthma management with appropriate inhaled medications and monitor closely with clinical review, chest radiograph, and serum total IgE every 3-6 months 1
• Exception: Consider treatment in asymptomatic patients with prolonged mucus plugging on CT scan, as this can progress to irreversible bronchiectasis 1, 3

ABPA-S (Serological ABPA without bronchiectasis)

• Manage primarily as asthma with high-dose inhaled corticosteroids and bronchodilators 2, 3
• Reserve systemic therapy only for poor asthma control or recurrent exacerbations despite optimal asthma management 2, 3

ABPA-B (with bronchiectasis), ABPA-MP (with mucus plugging), or ABPA-HAM (with high-attenuation mucus)

• Require systemic therapy with either oral prednisolone or itraconazole 3

First-Line Treatment Options for Acute ABPA

Oral Prednisolone Protocol

• Dosing: 0.5 mg/kg/day for 2-4 weeks, then taper and complete over 4 months total 1, 2, 3
• This low-to-moderate dose protocol results in fewer adverse events compared to high-dose regimens (0.75 mg/kg/day), with similar exacerbation rates 1
• Monitor for osteopenia and correct vitamin D deficiency to minimize bone loss 2
• Critical warning: Never combine methylprednisolone with itraconazole due to high risk of exogenous Cushing's syndrome and adrenal insufficiency 1, 3

Oral Itraconazole Protocol

• Dosing: 400 mg/day in two divided doses for 4 months 2, 3, 4
• Perform therapeutic drug monitoring with target trough level ≥0.5 mg/L 3
• Check monthly liver function tests throughout treatment 3
• Itraconazole is particularly useful when systemic glucocorticoids are contraindicated 2
• Evidence shows itraconazole reduces blood eosinophilia, serum total IgE, precipitating antibodies, and allows glucocorticoid dose reduction or elimination 4

Combination Therapy (Not First-Line)

• Do not use combination therapy as initial treatment 3
• A short course of glucocorticoids (<2 weeks) may be added initially when starting itraconazole to control symptoms, then transition to high-dose inhaled corticosteroids 1, 3
• Reserve combination therapy for patients with blood eosinophil count ≥1000 cells/μL and extensive bronchiectasis (≥10 segments) 2, 3

Monitoring Treatment Response

Initial Assessment (8-12 weeks)

• Evaluate clinical symptoms (≥50% improvement on Likert scale indicates good response) 2, 3
• Measure serum total IgE (should decrease by ≥35% from baseline for good response) 2, 3
• Obtain chest radiograph to assess for improvement 2, 3

Long-Term Monitoring

• Clinical review, serum total IgE levels, and lung function tests every 3-6 months 3
• Remission is defined as absence of pulmonary infiltrates and/or eosinophilia for 6 months after oral steroid withdrawal 3

Management of ABPA Exacerbations

Defining Exacerbations

• Sustained worsening (≥2 weeks) of clinical symptoms or new infiltrates on chest imaging 2, 3
• Plus serum total IgE increase ≥50% above the "new baseline" IgE established during clinical stability 2, 3
• Exacerbations occur in approximately 50% of patients after treatment cessation 2

Treatment of Exacerbations

• Treat the same as newly diagnosed acute ABPA with oral prednisolone or itraconazole 2, 3
• For recurrent exacerbations (≥2 in the last 1-2 years), consider combination therapy with oral prednisolone and itraconazole, especially with extensive bronchiectasis 2, 3
• Use chest radiographs, serum total IgE, and sputum bacterial cultures to differentiate ABPA exacerbations from asthma exacerbations or infective exacerbations of bronchiectasis 2, 3

Second-Line and Alternative Therapies

Alternative Azoles

• Voriconazole, posaconazole, and isavuconazole should not be used as first-line agents 3
• Consider only if contraindications to systemic glucocorticoids exist AND there is intolerance, failure, or resistance to itraconazole 3

Biological Agents

• Not recommended as first-line therapy 3
• Omalizumab may be considered for steroid-dependent patients (approximately 10-25% of ABPA patients) 3, 5
• Case reports show omalizumab provides steroid-sparing effects and decreases IgE levels in CF patients with ABPA 5
• Mepolizumab (anti-IL-5 antibody) has shown benefit in case reports for refractory ABPA, particularly when tapering corticosteroids is difficult 6
• Dupilumab may be an option for steroid-dependent patients 3

Critical Pitfalls to Avoid

• Never use high-dose inhaled corticosteroids alone as primary therapy for acute ABPA 3
• Never combine inhaled budesonide or fluticasone with itraconazole, as this can cause exogenous Cushing's syndrome 1, 3
• Never use methylprednisolone with itraconazole due to severe risk of Cushing's syndrome and adrenal insufficiency 1, 3
• Do not overlook asymptomatic patients with prolonged mucus plugging on CT, as they may require treatment to prevent irreversible bronchiectasis 3
• Do not confuse ABPA exacerbations with asthma exacerbations or bacterial bronchiectasis exacerbations—use serum total IgE trends and imaging to differentiate 2, 3