What are the guidelines for managing Allergic Bronchopulmonary Aspergillosis (ABPA)?

Guidelines for Managing Allergic Bronchopulmonary Aspergillosis (ABPA)

For managing Allergic Bronchopulmonary Aspergillosis (ABPA), oral prednisolone at 0.5 mg/kg/day for 2-4 weeks (tapered and completed over 4 months) or oral itraconazole for 4 months should be used as first-line therapy for acute ABPA, with treatment decisions based on radiological classification and symptom severity. 1

Diagnosis and Classification

ABPA is classified radiologically into five categories, which guide management:

1. Serological ABPA (ABPA-S): No bronchiectasis
2. ABPA with bronchiectasis (ABPA-B): Radiological evidence of bronchiectasis
3. ABPA with mucus plugging (ABPA-MP): Mucus plugging without high-attenuation mucus
4. ABPA with high-attenuation mucus (ABPA-HAM): High-attenuation mucus present
5. ABPA with chronic pleuropulmonary fibrosis (ABPA-CPF): Two or more of: pulmonary fibrosis, fibro-cavitary lesions, fungal ball, pleural thickening 1

Treatment Algorithm

Initial Treatment Decision

1. Asymptomatic ABPA:

   • Do not treat with systemic therapy 1

2. ABPA-S (Serological ABPA):

   • Treat like asthma with standard asthma medications
   • Add systemic therapy only if:
     • Poor asthma control despite optimal asthma therapy
     • Recurrent exacerbations despite optimal asthma management 1, 2

3. Symptomatic ABPA (ABPA-B, ABPA-MP, ABPA-HAM, ABPA-CPF):

   • First-line options (choose one):

     • Oral prednisolone: 0.5 mg/kg/day for 2-4 weeks, then tapered and completed over 4 months
     • Oral itraconazole: 200 mg daily for 4 months 1, 2

   • When to choose itraconazole over prednisolone:

     • When systemic glucocorticoids are contraindicated
     • In patients requiring continuous or frequent courses of systemic corticosteroids
     • In patients with frequent exacerbations (≥2 in the last 1-2 years)
     • In patients with extensive bronchiectasis 1, 2

Monitoring Treatment Response

Monitor after 8-12 weeks using:

• Clinical symptoms (goal: ≥50% improvement)
• Serum total IgE (goal: ≥20% reduction)
• Chest radiographs (goal: improvement in infiltrates) 1

Management of Exacerbations

ABPA exacerbations are characterized by:

• Sustained worsening (≥2 weeks) of clinical symptoms OR
• New infiltrates on chest imaging AND
• Increase in serum total IgE by ≥50% above baseline 1

Treatment of exacerbations:

• First exacerbation: Treat like newly diagnosed ABPA (prednisolone or itraconazole)
• Recurrent exacerbations (≥2 in 1-2 years): Use combination of oral prednisolone and itraconazole, especially in patients with extensive bronchiectasis 1

Important Considerations

Therapeutic Drug Monitoring

• For itraconazole: Target trough levels ≥0.5 mg/L
• For voriconazole/posaconazole: Target trough levels ≥1 mg/L 1, 2

Medications to Avoid as First-Line Therapy

• Do not use high-dose inhaled corticosteroids (ICS) alone as primary therapy 1, 3
• Do not use oral voriconazole, posaconazole, or isavuconazole as first-line agents 1
• Do not use biological agents as first-line therapy 1
• Do not use nebulized amphotericin B (poor efficacy) 1
• Do not use combination of itraconazole and glucocorticoids as first-line therapy 1

Potential Pitfalls

• Treating asymptomatic patients with systemic therapy
• Using high-dose ICS alone for ABPA-S (shown to be ineffective) 3
• Inadequate monitoring of therapeutic drug levels for azoles
• Overlooking drug interactions (particularly between azoles and corticosteroids)
• Failure to differentiate between asthma exacerbation, ABPA exacerbation, and infective exacerbation of bronchiectasis 1, 2

Special Considerations

• Methylprednisolone combined with oral itraconazole has higher risk of exogenous Cushing's syndrome and adrenal insufficiency 1
• Vitamin D deficiency should be corrected as it aggravates osteopenia due to long-term glucocorticoid usage 1
• Prednisolone decreases plasma concentration of voriconazole in a dose-dependent fashion 1

By following these guidelines, clinicians can effectively manage ABPA while minimizing disease progression and treatment-related adverse events.