What is the drug of choice for allergic bronchopulmonary aspergillosis (ABPA) in addition to systemic corticosteroids?

Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)

Itraconazole is the drug of choice for allergic bronchopulmonary aspergillosis (ABPA) in addition to systemic corticosteroids. 1

Diagnosis and Clinical Presentation

The 17-year-old patient presents with classic features of ABPA:

• History of asthma
• Fever and respiratory symptoms
• Elevated eosinophil count (1100 cells/μL)
• Markedly elevated total IgE (1200 IU/mL)
• Positive skin prick test to Aspergillus
• Radiographic findings showing bronchiectasis and upper lobe opacities

These findings meet the diagnostic criteria for ABPA, specifically ABPA with bronchiectasis (ABPA-B) based on the CT findings of right-sided bronchiectasis.

Treatment Approach

First-Line Therapy

The treatment of ABPA should consist of a combination of:

1. Systemic corticosteroids:

   • Prednisolone 0.5 mg/kg/day for 2-4 weeks
   • Tapered over 4 months
   • Provides rapid symptom relief and controls inflammation 1

2. Itraconazole:

   • Dosage: 400 mg/day in two divided doses for 4 months 1
   • Mechanism: Reduces fungal burden in airways, decreasing antigenic stimulation
   • Evidence level: A-I (highest recommendation) 1

Rationale for Itraconazole

Itraconazole is specifically recommended for ABPA because:

• It has a steroid-sparing effect, allowing for lower doses of corticosteroids 1, 2
• It reduces the frequency of ABPA exacerbations 2, 3
• It improves pulmonary function tests and exercise tolerance 2, 3
• It decreases serum IgE levels and blood eosinophilia 3

A randomized controlled trial by Stevens et al. demonstrated that 46% of patients receiving itraconazole had significant improvement compared to 19% in the placebo group (p=0.04) 2.

Monitoring and Follow-up

• Assess treatment response after 8-12 weeks using:

  • Clinical improvement (≥50% symptom reduction)
  • Chest radiograph improvement
  • ≥20% reduction in serum total IgE 1

• Monitor for adverse effects:

  • Liver function tests
  • Therapeutic drug monitoring (target itraconazole level >0.5 μg/mL) 1, 4
  • Drug interactions, particularly with inhaled fluticasone (patient is on fluticasone) 5

Why Not Other Options?

• Micafungin: Not indicated for ABPA; primarily used for invasive fungal infections
• Fluconazole: Poor activity against Aspergillus species
• Amphotericin-B: Too toxic for long-term use; reserved for invasive disease; nebulized formulation may be considered as maintenance therapy but not as initial therapy 1

Special Considerations for This Patient

• The patient is on inhaled fluticasone, which can interact with itraconazole, potentially causing Cushing's syndrome 1, 5
• Consider monitoring for signs of adrenal suppression or switching to a different inhaled corticosteroid
• Given the patient's young age (17), monitor for growth effects of prolonged corticosteroid use
• The presence of bronchiectasis indicates more advanced disease, making combination therapy particularly important

Treatment-Dependent ABPA

If the patient develops treatment-dependent ABPA (requiring long-term therapy):

• Consider maintenance with lower dose itraconazole (200 mg daily) 4
• Biological agents (omalizumab, mepolizumab, benralizumab, dupilumab) may be considered based on the patient's phenotype 1, 4
• Nebulized amphotericin B may be used as maintenance therapy 1

Conclusion

For this 17-year-old patient with ABPA, the optimal treatment approach is a combination of systemic corticosteroids and itraconazole, with careful monitoring of drug interactions due to his concurrent fluticasone therapy.