What is a detailed oral steroid prescription (prednisolone) for an adult with allergic bronchopulmonary aspergillosis, including initial dose, taper schedule, monitoring, and alternative therapy?

Oral Prednisolone Prescription for ABPA in Adults

Start prednisolone at 0.5 mg/kg/day for 2-4 weeks, then taper gradually to complete a total 4-month course, monitoring serum total IgE every 6-8 weeks to guide the taper. 1, 2, 3

Initial Dosing

• Calculate the starting dose: For a 70 kg adult, prescribe prednisolone 35 mg (0.5 mg/kg) orally once daily for 2-4 weeks 1, 2
• Take the medication in the morning with food to minimize gastric irritation 1
• This initial phase aims to rapidly control inflammation, reduce eosinophilia, and resolve pulmonary infiltrates 4

Tapering Schedule

The British Thoracic Society and European Respiratory Society describe two acceptable tapering approaches 1:

Option 1: Shorter Taper (Recommended for most patients)

• Weeks 1-2: Prednisolone 0.5 mg/kg/day (e.g., 35 mg daily) 1, 2
• Weeks 3-10: Switch to alternate-day dosing at 0.5 mg/kg (e.g., 35 mg every other day) 1
• Weeks 11-16: Taper by 5-10 mg every 2 weeks until discontinuation 1
• Total duration: 3-5 months 1

Option 2: Prolonged Taper (For severe disease or extensive bronchiectasis)

• Weeks 1-6: Prednisolone 0.75 mg/kg/day (e.g., 50 mg daily for 70 kg patient) 1
• Weeks 7-12: Reduce to 0.5 mg/kg/day (e.g., 35 mg daily) 1
• Weeks 13+: Taper by 5 mg every 6 weeks to complete at least 6-12 months total 1

Monitoring During Treatment

• Serum total IgE: Check every 6-8 weeks as the primary marker of disease activity 1, 2
  • A ≥35% reduction from baseline indicates good response 3, 5
  • A ≥50% rise above the patient's stable baseline suggests exacerbation 3
• Clinical assessment: Evaluate respiratory symptoms, asthma control, and functional status at each visit 2, 3
• Chest radiograph: Repeat at 8-12 weeks to assess resolution of infiltrates 3, 5
• Pulmonary function tests: Monitor FEV₁ for improvement (≥158 mL is clinically significant) 3
• Blood eosinophil count: Track alongside IgE levels 1

Adjusting the Taper Based on Response

• If IgE is declining and symptoms improving: Continue the planned taper 2, 3
• If IgE plateaus or rises during taper: Slow the taper or briefly increase the dose, then resume tapering more gradually 1
• If clinical deterioration occurs: Consider this an ABPA exacerbation and restart treatment (see below) 3, 5

Definition of Remission

• Patients achieve remission when they remain without pulmonary infiltrates and/or eosinophilia for 6 months after complete steroid withdrawal 1, 5

Steroid-Related Adverse Effects to Monitor

• Metabolic: Hyperglycemia, weight gain, hypertension—check blood pressure and glucose regularly 1
• Bone health: Osteoporosis risk—prescribe calcium 1000-1500 mg/day and vitamin D 800-1000 IU/day from day one 1, 6
• Other: Cushingoid features, mood changes, gastritis, cataracts, opportunistic infections 1

Alternative First-Line Therapy: Itraconazole Monotherapy

If systemic corticosteroids are contraindicated or the patient refuses steroids, prescribe itraconazole 400 mg/day (200 mg twice daily with meals) for 4 months as an alternative first-line option. 1, 3, 5

• Use conventional itraconazole capsules 200 mg twice daily with meals to enhance absorption 1
• Therapeutic drug monitoring: Check trough levels after 2 weeks (target ≥0.5 mg/L, ideally 1-2 mg/L) 1, 5
• Liver function tests: Monitor monthly due to hepatotoxicity risk 1, 5
• Maximum dose: 600 mg/day if needed 1

Critical Drug Interaction Warning

• Never combine itraconazole with methylprednisolone—this combination markedly increases the risk of exogenous Cushing's syndrome and adrenal insufficiency 1, 3, 5
• Avoid high-dose inhaled corticosteroids (budesonide, fluticasone) with itraconazole due to cytochrome P450 inhibition causing adrenal suppression 3, 5
• Prednisolone levels are not significantly affected by itraconazole, making it the preferred corticosteroid if combination therapy is needed 1

When to Use Combination Therapy (Prednisolone + Itraconazole)

Combination therapy is NOT recommended as first-line treatment for newly diagnosed ABPA. 3, 5 However, consider adding itraconazole to prednisolone in these specific scenarios:

• Recurrent exacerbations: ≥2 ABPA exacerbations in the past 1-2 years 3, 5
• Extensive bronchiectasis: Involvement of ≥10 lung segments on CT 3, 5
• Severe eosinophilia with bronchiectasis: Blood eosinophil count ≥1000 cells/µL plus extensive bronchiectasis 3, 5
• Steroid-dependent disease: Difficulty weaning from corticosteroids or relapse with dose reduction 1

When initiating combination therapy, you may use a short (<2 weeks) course of oral prednisolone for rapid symptom control, then transition to high-dose inhaled corticosteroids once symptoms improve 3

Management of ABPA Exacerbations

An ABPA exacerbation is defined by all three of the following 3:

1. Persistent worsening of respiratory symptoms for ≥2 weeks
2. New pulmonary infiltrates on chest imaging
3. Serum total IgE rise ≥50% above the patient's stable baseline

Treat exacerbations identically to newly diagnosed ABPA: restart prednisolone 0.5 mg/kg/day or itraconazole 400 mg/day for 4 months 3, 5

For patients with recurrent exacerbations, escalate to combination therapy with both prednisolone and itraconazole 3, 5

Second-Line Antifungal Options

If itraconazole fails, is not tolerated, or resistance develops, consider 1, 3, 5:

• Voriconazole: 400 mg/day (200 mg twice daily) on an empty stomach, maximum 600 mg/day 1
• Posaconazole: 800 mg/day (oral suspension in two divided doses with meals) or 300 mg/day (delayed-release tablet once daily) 1
• Isavuconazole: 200 mg once daily, no food restrictions 1

These agents should not be used first-line but are reserved for specific circumstances 3, 5

Role of Inhaled Corticosteroids

• High-dose inhaled corticosteroids alone do NOT control ABPA and should not be used as primary therapy 1, 3
• Inhaled corticosteroids may serve as a useful adjunct to oral steroids for better asthma symptom control 1
• Some case reports suggest inhaled corticosteroids can help wean patients from high-dose oral steroids, but this is not standard practice 1, 7

Steroid-Sparing Biological Agents

For treatment-dependent ABPA (10-25% of patients who cannot discontinue therapy without relapse) 3, 5:

• Omalizumab: Dose based on body weight and serum IgE (not exceeding 375 mg subcutaneously twice monthly) 1, 3
• Mepolizumab: 100 mg subcutaneously monthly 1
• Dupilumab: 600 mg subcutaneously loading dose, then 300 mg every 2 weeks 1, 3

Biologics are not first-line but may be considered for patients requiring ongoing therapy despite conventional treatment 3, 5

Common Pitfalls to Avoid

• Tapering too quickly: This leads to relapse—always taper slowly by 5 mg decrements every 2-6 weeks 1
• Ignoring IgE trends: A rising IgE during taper signals impending exacerbation—slow or reverse the taper 1, 2
• Failing to distinguish ABPA exacerbation from asthma exacerbation: ABPA exacerbations require IgE rise and new infiltrates, not just worsening dyspnea 3
• Using methylprednisolone with itraconazole: This combination causes severe Cushing's syndrome—always use prednisolone instead 1, 3, 5
• Undertreating asymptomatic patients with mucus plugging: Even without symptoms, prolonged mucus plugging requires treatment to prevent irreversible bronchiectasis 2, 5
• Forgetting bone protection: Always prescribe calcium and vitamin D when starting corticosteroids 1, 6

Special Populations

• ABPA-S (serological ABPA without bronchiectasis): Manage as asthma with inhaled therapies; reserve systemic ABPA treatment only for poor asthma control or recurrent exacerbations 3, 5
• Asymptomatic ABPA: No systemic therapy required—optimize asthma control and monitor every 3-6 months 3, 5
• ABPA with mucus plugging or high-attenuation mucus: Requires systemic treatment even if asymptomatic to prevent progression 2, 3, 5