ABPA, Allergic Bronchopulmonary Aspergillosis

Decision points

• Are the ISHAM diagnostic criteria met?
• Is the disease active or in remission?

Do-not-miss pitfalls

• Total serum IgE >=500 IU/mL is the obligatory threshold under the 2024 ISHAM revision (lowered from 1000), order it in any poorly controlled asthmatic with recurrent exacerbations, central bronchiectasis, or mucus plugging. Using the old 1000 cut-off will miss real cases; missing the test entirely is the commonest reason ABPA goes undiagnosed.
• A normal or low total IgE essentially excludes active ABPA (except in patients already on systemic corticosteroids, which suppress IgE). Do not diagnose active ABPA with a normal IgE.
• ABPA is distinct from severe asthma with fungal sensitization (SAFS): SAFS has Aspergillus sensitization but does not meet the total-IgE threshold or carry the precipitin and radiographic burden of ABPA. The distinction changes treatment.
• Itraconazole has major drug interactions (CYP3A4), it dramatically raises levels of inhaled/systemic corticosteroids (risk of iatrogenic Cushing/adrenal suppression), and interacts with many asthma and cardiac drugs. Check interactions and consider therapeutic drug monitoring.
• Central bronchiectasis and mucus plugging (high-attenuation mucus) are characteristic radiographic features, order HRCT, not just chest X-ray, when ABPA is suspected.
• Serial total IgE is the monitoring biomarker, NOT Aspergillus-specific IgE. Track against the patient’s own baseline: a >=50% RISE with clinical or radiographic change defines an exacerbation, while a fall of roughly 35-50% is what treatment response looks like. Do not read the two directions interchangeably.
• Long-term systemic corticosteroids cause significant harm, escalate to itraconazole and biologics (omalizumab, mepolizumab) to spare steroids in dependent/relapsing disease.
• ABPA in cystic fibrosis is harder to diagnose because baseline bronchiectasis and elevated IgE overlap with CF itself, use a higher index of suspicion and trend IgE against the patient's CF baseline.

Evidence & citations

1. Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013;43(8):850-873. PMID 23889240
2. Stevens DA, Schwartz HJ, Lee JY, et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med. 2000;342(11):756-762. PMID 10717010
3. Agarwal R, Aggarwal AN, Dhooria S, et al. A randomised trial of glucocorticoids in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Eur Respir J. 2016;47(2):490-498. PMID 26585431
4. Agarwal R, Sehgal IS, Muthu V, et al. Revised clinical practice guidelines for diagnosing, classifying, and treating allergic bronchopulmonary aspergillosis/mycoses: an ISHAM-ABPA working group report. Eur Respir J. 2024;63(4):2400061. PMID 38423624