In a 46-year-old woman with severe uncontrolled asthma on high-dose LABA/ICS, ACT score 10, multiple intubated exacerbations, finger clubbing, coarse crepitations, total IgE 1200 IU/mL, Aspergillus‑specific IgE 0.40 kU/L, eosinophils 600 cells/µL, and CT showing finger‑in‑glove mucoid impaction, what is the best next management?

Management of Allergic Bronchopulmonary Aspergillosis (ABPA)

This patient requires systemic corticosteroids (Option D) as first-line therapy for acute ABPA with mucoid impaction. 1

Clinical Diagnosis

This patient presents with classic acute ABPA based on:

• Severe uncontrolled asthma (ACT score 10) with multiple intubated exacerbations 1
• Markedly elevated total IgE (1200 IU/mL, normal <300) 1
• Positive Aspergillus fumigatus-specific IgE (0.40 kU/L) 1
• Peripheral eosinophilia (600 cells/µL) 1
• Pathognomonic CT finding of "finger-in-glove" mucoid impaction 1
• Finger clubbing and coarse crepitations suggesting advanced disease with bronchiectasis 1

Why Systemic Corticosteroids Are First-Line

Oral glucocorticoids are the most rapid-acting treatment for acute ABPA and should be initiated immediately. 1 The 2024 ISHAM-ABPA Working Group guidelines recommend a 4-month course of low-to-moderate dose oral prednisolone (0.5 mg/kg/day for 2-4 weeks, then tapered over 4 months) as first-line therapy for acute ABPA. 1

Evidence Supporting Corticosteroids:

• Symptoms of wheezing, dyspnea, and cough remit rapidly with corticosteroid therapy 1
• Corticosteroids are essential for treating acute asthmatic exacerbations and preventing progression to end-stage fibrotic disease 1
• The patient's severe presentation with multiple intubations and mucoid impaction requires the fastest-acting therapy 1

Why Other Options Are Incorrect

Option A (Long-acting anti-muscarinic inhaler):

• High-dose inhaled corticosteroids should not be used as primary therapy for acute ABPA (Level of Consensus: 100%) 1
• Adding a LAMA addresses only the asthma component, not the underlying ABPA pathophysiology 1
• This patient is already on maximal inhaled therapy (high-dose LABA+ICS) with poor control 1

Option B (Omalizumab):

• Biological agents should not be used as first-line therapy for acute ABPA (Level of Consensus: 96.9%) 1
• Omalizumab is reserved for treatment-dependent ABPA (patients requiring ongoing therapy after initial treatment) or as steroid-sparing therapy 2
• While omalizumab has shown benefit in case reports, it is not appropriate for acute presentation with mucoid impaction 2, 3, 4

Option C (Systemic antifungal):

• Oral itraconazole is an acceptable alternative to corticosteroids but has a slower trajectory to improvement 1
• The 2024 guidelines recommend itraconazole primarily when systemic glucocorticoids are contraindicated (Level of Consensus: 84.6%) 1
• Given this patient's severe presentation with multiple intubations and active mucoid impaction, the rapid action of corticosteroids is preferred 1
• Itraconazole may be added after initial corticosteroid therapy for steroid-sparing effect 1, 5

Treatment Algorithm

Immediate Management:

1. Initiate oral prednisolone 0.5 mg/kg/day for 2-4 weeks 1
2. Continue high-dose LABA+ICS for underlying asthma control 1
3. Monitor response at 8-12 weeks using clinical symptoms, serum total IgE, and chest radiographs 1

Tapering Strategy:

• After 2-4 weeks, taper prednisolone gradually over 4 months total duration 1
• A good response is indicated by ≥50% improvement in symptoms and ≥20% reduction in serum total IgE 1

Consider Adding Itraconazole:

• If patient develops steroid-dependent ABPA or has recurrent exacerbations (≥2 in 1-2 years), add oral itraconazole 200 mg twice daily for steroid-sparing effect 1
• Combination therapy (prednisolone + itraconazole) is recommended for recurrent exacerbations, especially with extensive bronchiectasis 1

Critical Pitfalls to Avoid

Do not use methylprednisolone with itraconazole due to high risk of exogenous Cushing's syndrome and adrenal insufficiency from drug interactions. 1 Similarly, avoid combining inhaled budesonide or fluticasone with itraconazole for the same reason. 1

Do not delay treatment in patients with mucoid impaction, as prolonged mucus plugging can progress to irreversible bronchiectasis. 1

Do not use nebulized amphotericin B for acute exacerbations as it has poor efficacy in this setting. 1

Long-Term Considerations

After achieving remission with corticosteroids, monitor every 3-6 months with clinical review, chest radiograph, and serum total IgE. 1 Nearly 50% of patients experience ABPA exacerbations after treatment cessation, which should be managed identically to newly diagnosed ABPA. 1

If the patient becomes treatment-dependent (requiring ongoing therapy to maintain control), consider transitioning to long-term itraconazole or biological agents like omalizumab for steroid-sparing effect. 1, 2