What is the typical diagnosis cascade for Allergic Bronchopulmonary Aspergillosis (ABPA) in children?

Diagnostic Cascade for Allergic Bronchopulmonary Aspergillosis (ABPA) in Children

The diagnosis of ABPA in children requires a systematic approach focusing on clinical, radiological, and immunological evaluations, with mandatory demonstration of fungal sensitization and serum total IgE ≥500 IU·mL−1 plus two additional criteria. 1

Step 1: Screening for ABPA in At-Risk Children

• Screen for Aspergillus fumigatus sensitization using fungus-specific IgE in difficult-to-treat asthmatic children 1
• Children with poorly controlled asthma should be investigated for ABPA 2
• Consider ABPA in children with cystic fibrosis, as approximately 7% develop ABPA 1
• Maintain high index of suspicion in children with asthma who present with unusual radiological findings, including mass-like lesions 3

Step 2: Clinical Evaluation

• Assess for characteristic symptoms:
  • Episodic wheezing and bronchial obstruction 1
  • Cough and breathlessness 1
  • Expectoration of brown plugs or flecks 1
  • Pyrexia 1
  • Fatigue and malaise 1

Step 3: Laboratory Investigations (Mandatory)

• Serum total IgE ≥500 IU·mL−1 (mandatory criterion) 1
• Aspergillus fumigatus-specific IgE (mandatory criterion) 1
• Complete at least two of the following additional tests:
  • Aspergillus fumigatus-specific IgG 1
  • Peripheral blood eosinophilia 1
  • Suggestive imaging findings 1

Step 4: Radiological Evaluation

• Chest CT is crucial but radiation dosage should be carefully considered in children 1
• Look for characteristic findings:
  • Central bronchiectasis (usually bilateral) 1
  • Transient pulmonary opacities/fleeting shadows 1
  • High-attenuation mucus (HAM) 1
  • Mucus plugging 1
  • Band shadows or glove-finger shadows 1
  • "Ring sign" or parallel "tram lines" 1

Step 5: Classification Based on Radiological Findings

• ABPA-S (Serological ABPA): No bronchiectasis 1
• ABPA-B (ABPA with bronchiectasis): Presence of bronchiectasis 1
• ABPA-MP (ABPA with mucus plugging): Presence of mucus plugs 1
• ABPA-HAM (ABPA with high-attenuation mucus): Presence of HAM 1
• ABPA-CPF (ABPA with chronic pleuropulmonary fibrosis): Advanced disease 1

Step 6: Clinical Classification

• Acute ABPA: Newly diagnosed or exacerbation 1
• Response: Symptomatic improvement by ≥50% after 8 weeks of treatment 1
• Remission: Sustained (≥6 months) clinico-radiological improvement off glucocorticoids 1
• Treatment-dependent ABPA: Two or more consecutive exacerbations within 3 months of stopping glucocorticoids 1
• Advanced ABPA: Extensive bronchiectasis with type 2 respiratory failure or pulmonary hypertension 1

Special Considerations in Pediatric ABPA Diagnosis

• Differentiate ABPA exacerbation from asthma exacerbation or infective/bronchiectasis exacerbation 1
• Consider alternative diagnoses for bronchiectasis (immunodeficiencies, ciliary disorders, mycobacterial infection) 1
• In children with extensive bronchiectasis and recurrent infections since childhood, consider whole-exome sequencing to identify primary ciliary dyskinesias, primary immunodeficiency, or atypical cystic fibrosis 1
• For cystic fibrosis patients, the overlap between CF and ABPA symptoms makes diagnosis challenging, requiring careful application of diagnostic criteria 4
• Be aware that ABPA in children may present atypically, including as mass-like lesions in the lung 3

Pitfalls and Caveats

• Delay in diagnosis is common in pediatric ABPA, leading to unnecessary invasive investigations and disease progression 3
• There is a lack of pediatric-specific cutoffs for diagnostic criteria in ABPA 5
• CT scans should be used judiciously in children due to radiation exposure concerns 1
• In cystic fibrosis patients, diagnostic confirmation cannot be divorced from clinical findings despite laboratory testing 4
• The detection of recombinant Aspergillus antigen-specific IgE can be a useful tool for early detection of sensitization and diagnosis 4

By following this systematic diagnostic cascade, clinicians can identify ABPA in children early, preventing progression to bronchiectasis and pulmonary fibrosis, which significantly impact morbidity, mortality, and quality of life 5.