What is the treatment for allergic broncho pulmonary aspergillosis (ABPA)?

Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)

For acute ABPA, initiate oral prednisolone 0.5 mg/kg/day for 2-4 weeks, then taper gradually over a total 4-month course, as this remains the most effective first-line treatment. 1

First-Line Treatment Options

Oral Corticosteroids (Preferred)

• Prednisolone 0.5 mg/kg/day for 2-4 weeks, then tapered and completed over 4 months is the recommended regimen for newly diagnosed acute ABPA 1, 2, 3
• This low-to-moderate dose protocol results in fewer adverse events compared to high-dose regimens, with similar exacerbation rates 1
• The typical taper involves: 0.5 mg/kg/day for 2-4 weeks → alternate day dosing for 8 weeks → reduce by 5 mg every 2 weeks until discontinuation 2
• Glucocorticoids are FDA-approved for ABPA and remain the most effective treatment for controlling the immune response 4

Oral Itraconazole (Alternative or Steroid-Sparing)

• Itraconazole 400 mg/day in two divided doses for 4 months is an alternative when systemic glucocorticoids are contraindicated or as a steroid-sparing agent 1, 3, 5
• Therapeutic drug monitoring is essential with target trough levels ≥0.5 mg/L 2, 3, 5
• Monthly liver function tests are mandatory during itraconazole therapy 2, 3, 5
• Some clinicians use a short course of glucocorticoids (<2 weeks) initially with itraconazole, then transition to high-dose inhaled corticosteroids once symptoms are controlled 1, 3

Treatment Based on Disease Classification

Asymptomatic ABPA (ABPA-S without bronchiectasis)

• Systemic therapy is not routinely required for asymptomatic patients 1, 3, 5
• Manage as asthma with appropriate asthma medications and high-dose inhaled corticosteroids 3, 5
• Important caveat: Asymptomatic patients with prolonged mucus plugging on CT should be treated to prevent progression to irreversible bronchiectasis 1, 3

Acute ABPA with Bronchiectasis, Mucus Plugging, or High-Attenuation Mucus

• Systemic therapy is required for all patients with ABPA-B, ABPA-MP, or ABPA-HAM 3
• Use the same treatment regimen as for acute ABPA (prednisolone or itraconazole) 3, 5

Combination Therapy Indications

Combination of oral prednisolone and itraconazole is NOT recommended as first-line therapy 3, 5, but should be considered in specific situations:

• Recurrent exacerbations (≥2 in the last 1-2 years) 3, 5
• Blood eosinophil count ≥1000 cells/μL with extensive bronchiectasis (≥10 segments) 2, 3, 5
• Steroid-dependent patients requiring ongoing therapy 3

Critical Drug Interaction Warnings

Avoid These Combinations:

• Never combine methylprednisolone with itraconazole due to significantly increased risk of exogenous Cushing's syndrome and adrenal insufficiency 1, 2, 3, 5
• Avoid combining high-dose inhaled budesonide or fluticasone with itraconazole as this can also cause exogenous Cushing's syndrome 1, 3

Monitoring Treatment Response

Initial Assessment (8-12 weeks)

• Clinical symptom improvement 3, 5
• Serum total IgE should decrease by ≥35% from baseline 3, 5
• Chest radiograph showing resolution of infiltrates 3, 5

Ongoing Monitoring

• Clinical review, serum total IgE levels, and lung function tests every 3-6 months 3, 5
• Remission is defined as absence of pulmonary infiltrates and/or eosinophilia for 6 months after oral steroid withdrawal 2, 3

Management of ABPA Exacerbations

ABPA exacerbations are characterized by sustained worsening (≥2 weeks) of clinical symptoms or new infiltrates on chest imaging, with serum total IgE increase ≥50% above baseline 3

• Treat exacerbations the same way as newly diagnosed ABPA with oral prednisolone or itraconazole 3, 5
• For recurrent exacerbations, strongly consider combination therapy with both prednisolone and itraconazole 3, 5

Second-Line and Biological Therapies

Alternative Antifungals

• Voriconazole, posaconazole, and isavuconazole should NOT be used as first-line agents 3
• Reserve these for cases with contraindications to systemic glucocorticoids AND intolerance, failure, or resistance to itraconazole 3

Biological Agents

• Omalizumab and dupilumab are NOT first-line therapies but may be considered for treatment-dependent ABPA (10-25% of patients) 3, 5, 6
• Omalizumab has demonstrated effectiveness and safety even in patients with chronic bacterial infections (P. aeruginosa or nontuberculous mycobacteria) 6
• No established fixed duration exists for dupilumab treatment; response is indicated by major symptom improvement and ≥20% reduction in serum total IgE 5

Common Pitfalls to Avoid

• Do not use high-dose inhaled corticosteroids alone as primary therapy for acute ABPA 3—while older studies suggested benefit 7, 8, current guidelines prioritize systemic therapy for acute disease
• Do not overlook the need to treat asymptomatic patients with mucus plugging on CT, as this can progress to irreversible bronchiectasis 1, 3
• Do not fail to distinguish between asthma exacerbations, ABPA exacerbations, and infective exacerbations of bronchiectasis, as these require different management approaches 3
• Do not use fluconazole, as it has not demonstrated significant benefit compared to itraconazole 9