Allergic Bronchopulmonary Aspergillosis (ABPA)

I. Introduction & Definition

• Definition: A complex pulmonary hypersensitivity reaction (Type I, III, and IV) to the colonization of the airways by the fungus Aspergillus fumigatus.
• Key Concept: It is an allergic response, not an invasive infection.
• Predisposing Conditions:
  • Cystic Fibrosis (CF): Prevalence up to 15%.
  • Asthma: Prevalence 1–2% in asthmatics.

II. Pathophysiology

1. Colonization: A. fumigatus spores are inhaled and trapped in the viscid mucus of susceptible hosts (Asthma/CF).
2. Antigen Release: The fungus germinates and releases proteolytic enzymes and antigens.
3. Immune Response:
   • Th2 Response: intense production of Interleukins (IL-4, IL-5, IL-13).
   • IgE Production: Massive polyclonal and specific IgE synthesis.
   • Eosinophilia: Eosinophilic infiltration of bronchial wall.
4. Tissue Damage: Immune complexes and inflammatory mediators lead to mucus hypersecretion, airway damage, and eventually Central Bronchiectasis.

III. Clinical Features

• History: Child with poorly controlled asthma or CF despite optimal therapy.
• Symptoms:
  • Wheezing: Recurrent exacerbations.
  • Cough: Productive of brownish/black mucus plugs (golden-brown casts).
  • Systemic: Low-grade fever, malaise, weight loss.
  • Hemoptysis: Occasional (from bronchiectasis).
• Physical Signs: Polyphonic wheeze, crackles (if bronchiectasis present), clubbing (late sign).

IV. Diagnosis

Diagnosis relies on a combination of clinical, serological, and radiological findings.

A. Diagnostic Criteria (ISHAM Working Group, 2013)

Current standard, replacing the older Rosenberg-Patterson criteria.

1. Predisposing Condition: Asthma or Cystic Fibrosis.

2. Mandatory Criteria (Both required):

• Positive Type I skin test (cutaneous hypersensitivity) to Aspergillus OR Elevated specific IgE against A. fumigatus.
• Elevated Total Serum IgE (>1000 IU/mL).

3. Supporting Criteria (At least 2 of 3):

• Precipitating IgG antibodies (Precipitins) to A. fumigatus.
• Radiographic pulmonary opacities consistent with ABPA.
• Total Eosinophil Count >500 cells/µL.

B. Radiological Features

1. Chest X-Ray:
   • "Finger-in-Glove" sign: Mucoid impaction in dilated bronchi.
   • "Tram-track" lines: Bronchial wall thickening.
   • Fleeting/transient pulmonary infiltrates (migratory).
2. HRCT Chest (Gold Standard):
   • Central Bronchiectasis: Dilatation of proximal bronchi with normal peripheral tapering (Pathognomonic).
   • High Attenuation Mucus (HAM): Mucus plugs that appear denser than muscle (predicts relapse).

V. Staging (Patterson’s Stages)

Used to guide management and follow-up.

VI. Management

1. Goals

• Control inflammation (Steroids).
• Reduce fungal burden (Antifungals).
• Prevent progression to fibrosis (Stage V).

2. Corticosteroids (The Mainstay)

• Drug: Oral Prednisolone.
• Dose:
  • Acute (Stage I/III): 0.5 – 0.75 mg/kg/day for 2–4 weeks.
  • Tapering: Gradual weaning over 3–6 months based on clinical response and IgE decline.
• Monitoring: Total Serum IgE levels are checked every 6–8 weeks. A decline >35% indicates remission.

3. Antifungal Agents (Adjunct/Sparing)

• Indication: To reduce fungal antigenic load, allowing for steroid tapering (Steroid-sparing effect).
• Drug: Itraconazole.
• Dose: 5 mg/kg/day (Max 200 mg BD) for 4–6 months.
• Note: Monitor liver enzymes; Itraconazole levels can be erratic (absorption requires acidic pH).
• Alternative: Voriconazole or Posaconazole (if resistant/intolerant).

4. Biologics (Recent Advances)

• Omalizumab (Anti-IgE): Monoclonal antibody. Can be effective in refractory Stage IV ABPA to reduce steroid requirement.
• Mepolizumab (Anti-IL5): Investigational for ABPA.

VII. Prognosis & Complications

• Prognosis: Good if treated in Stage I/II.
• Complications:
  • Central Bronchiectasis (Permanent).
  • Pulmonary Fibrosis / Cor Pulmonale (Stage V).
  • Side effects of long-term steroids (Cushingoid, growth failure).