Allergic Bronchopulmonary Aspergillosis (ABPA)
Introduction And Predisposing Factors
- Complex pulmonary hypersensitivity reaction involving Type I, Type III, and Type IV responses.
- Triggered by airway colonization by fungus Aspergillus fumigatus.
- Represents allergic response, not invasive infection.
- Predisposing conditions include Cystic Fibrosis (prevalence up to 15%) and Asthma (prevalence 1-2%).
- Rarely occurs in Cystic Fibrosis children under 6 years of age.
Pathophysiology
- Colonization: Aspergillus fumigatus spores inhaled, trapped in viscid mucus of susceptible hosts.
- Antigen Release: Fungus germinates, releasing proteolytic enzymes and antigens.
- Immune Response: Intense T-helper 2 response produces Interleukin-4, Interleukin-5, and Interleukin-13.
- Massive polyclonal and specific Immunoglobulin E synthesis occurs.
- Eosinophilic infiltration of bronchial wall develops.
- Tissue Damage: Immune complexes and inflammatory mediators cause mucus hypersecretion, airway damage, and eventually central bronchiectasis.
Clinical Features
- Poorly controlled asthma or Cystic Fibrosis despite optimal therapy.
- Recurrent wheezing exacerbations.
- Cough productive of brownish-black mucus plugs, golden-brown casts, or rust-colored sputum.
- Occasional hemoptysis resulting from bronchiectasis.
- Systemic signs include low-grade fever, malaise, weight loss.
- Physical signs include polyphonic wheeze, crackles, late-stage clubbing.
Diagnostic Criteria (Isham Working Group 2013)
Predisposing Condition
Mandatory Criteria
- Requires both:
- Positive Type I skin test to Aspergillus or elevated specific Immunoglobulin E against Aspergillus fumigatus.
- Elevated total serum Immunoglobulin E (>1000 International Units/mL).
Supporting Criteria
- Requires at least two:
- Precipitating Immunoglobulin G antibodies to Aspergillus fumigatus.
- Radiographic pulmonary opacities consistent with Allergic Bronchopulmonary Aspergillosis.
- Total eosinophil count >500 cells/Β΅L.
Radiological Features
Chest Radiograph
- Finger-in-glove sign indicating mucoid impaction in dilated bronchi.
- Tram-track lines representing bronchial wall thickening.
- Fleeting or transient migratory pulmonary infiltrates.
High-Resolution Computed Tomography
- Gold standard modality.
- Central bronchiectasis (pathognomonic finding).
- High attenuation mucus indicating mucus plugs denser than skeletal muscle (predicts clinical relapse).
Patterson Staging
| Stage | Name | Clinical Features | Immunoglobulin E Level | Management |
|---|---|---|---|---|
| I | Acute | Typical symptoms, infiltrates | Very High | Corticosteroids |
| II | Remission | Asymptomatic, clear radiograph | Drops 35-50% | Observe |
| III | Exacerbation | Recurrence of symptoms/infiltrates | Doubles | Resume Corticosteroids |
| IV | Corticosteroid-Dependent | Asthma worsens on weaning | Persistently High | Corticosteroids + Antifungals |
| V | Fibrotic | Irreversible fibrosis, respiratory failure | Variable | Supportive Care |
Management
Treatment Goals
- Control inflammation.
- Reduce fungal burden.
- Prevent progression to irreversible fibrosis.
Pharmacotherapy
- Corticosteroids: Mainstay therapy.
- Oral Prednisolone 0.5-0.75 mg/kg/day for 2-4 weeks during acute phase.
- Gradual tapering over 3-6 months based on clinical response.
- Monitor total serum Immunoglobulin E every 6-8 weeks (>35% decline indicates remission).
- Antifungal Agents: Adjunct, steroid-sparing therapy.
- Itraconazole 5 mg/kg/day (maximum 200 mg twice daily) for 4-6 months.
- Monitor liver enzymes and drug levels.
- Alternatives include Voriconazole or Posaconazole.
- Biologics:
- Omalizumab (Anti-Immunoglobulin E) for refractory Stage IV disease.
- Mepolizumab (Anti-Interleukin-5) investigational use.
Complications And Prognosis
- Good prognosis if treated in Stage I or II.
- Permanent central bronchiectasis.
- Pulmonary fibrosis and cor pulmonale in Stage V.
- Side effects of long-term corticosteroids including Cushingoid features and growth failure.