What is the diagnostic workup and treatment for a patient with suspected allergic broncho pulmonary aspergillosis, history of asthma or cystic fibrosis, and possible previous diagnosis of strongyloidiasis?

Diagnostic Workup for Allergic Bronchopulmonary Aspergillosis

Begin with serum A. fumigatus-specific IgE testing (≥0.35 kUA·L⁻¹) and if positive, proceed with serum total IgE (≥500 IU·mL⁻¹), A. fumigatus-specific IgG, peripheral blood eosinophil count (≥500 cells·μL⁻¹), and thin-section chest CT to establish the diagnosis. 1

Initial Serological Testing Algorithm

For patients with asthma, cystic fibrosis, COPD, or bronchiectasis presenting with treatment-resistant symptoms or recurrent infiltrates, measure A. fumigatus-specific IgE first. 1, 2

• If A. fumigatus-specific IgE is ≥0.35 kUA·L⁻¹, proceed to measure serum total IgE 1
• If serum total IgE is ≥500 IU·mL⁻¹, continue with complete ABPA workup 1
• If A. fumigatus-specific IgE is <0.35 kUA·L⁻¹ but clinical suspicion remains high, consider ABPM (allergic bronchopulmonary mycosis from non-Aspergillus fungi) 1

Essential Diagnostic Components

The 2024 revised ISHAM-ABPA working group criteria require two essential components plus any two additional components for diagnosis. 1, 2

Essential Components (both required):

• A. fumigatus-specific IgE ≥0.35 kUA·L⁻¹ 1
• Serum total IgE ≥500 IU·mL⁻¹ 1

Additional Components (any two required):

• Positive IgG against A. fumigatus (use population-specific cut-offs; when unavailable, use manufacturer-recommended cut-offs) 1
• Blood eosinophil count ≥500 cells·μL⁻¹ (can be historical) 1
• Thin-section chest CT findings consistent with ABPA (bronchiectasis, mucus plugging, high-attenuation mucus) or fleeting opacities on chest radiograph 1

Imaging Studies

Obtain thin-section chest CT at baseline to identify bronchiectasis, mucus plugging, high-attenuation mucus (HAM), and other abnormalities. 1

• High-attenuation mucus is pathognomonic for ABPA and confirms diagnosis even if other criteria are not completely fulfilled 2
• Use chest radiograph (not CT) for follow-up and treatment response assessment 1
• CT findings may include central bronchiectasis, mucoid impaction, consolidations, centrilobular nodules with tree-in-bud pattern, atelectasis, and mosaic attenuation 1, 3

Microbiological Testing

Obtain sputum for fungal culture during evaluation, particularly for ABPM where it is mandatory. 1

• Sputum fungal culture is suggested for ABPA to identify species and guide therapy 1
• Sputum fungal culture is essential for ABPM diagnosis, requiring at least two positive sputum cultures or one positive bronchoalveolar lavage fluid culture 1
• Do not use serum galactomannan for diagnosing ABPA 1

Bronchoscopy Indications

Bronchoscopy is not routinely recommended but should be performed in specific situations. 1

Perform bronchoscopy when:

• Diagnosis remains uncertain after initial workup 1
• Suspected ABPM with uninformative or unobtainable sputum cultures 1
• Unexplained hemoptysis is present 1
• Suspicion of chronic tuberculous or non-tuberculous mycobacterial infection exists before initiating systemic glucocorticoids 1
• Therapeutic removal of mucus plugs is needed in respiratory failure or recalcitrant mucus plugs despite systemic therapy 1

Special Considerations for Strongyloidiasis History

In patients with possible previous strongyloidiasis, exclude active infection before initiating systemic glucocorticoids to prevent hyperinfection syndrome. [General Medicine Knowledge]

• Obtain stool examination and Strongyloides serology before starting corticosteroids
• Consider empiric ivermectin treatment if strongyloidiasis cannot be definitively excluded and corticosteroids are urgently needed

Diagnostic Pitfalls and Caveats

Several conditions can mimic or coexist with ABPA, requiring careful differentiation. 1

• A. fumigatus-specific IgE and IgG can be elevated in COPD, pulmonary tuberculosis, and bronchiectasis without ABPA 1
• Chronic pulmonary aspergillosis may have raised A. fumigatus-IgE, total IgE, and A. fumigatus-IgG 1
• Aspergillus bronchitis shows positive respiratory cultures and raised A. fumigatus-IgG but does not fulfill ABPA criteria 1
• Severe asthma with fungal sensitization has elevated total IgE and Aspergillus sensitization but lacks other ABPA criteria 1
• Low serum total IgE can occur with prior glucocorticoid treatment, in elderly patients, or in those with constitutively low IgE 1
• Non-standardized assays for IgE and IgG can lead to misclassification of ABPA as ABPM 1

Workup for Alternative Causes of Bronchiectasis

Search for other causes of bronchiectasis in all ABPA patients, as multiple etiologies can coexist. 1

Perform:

• Complete blood count 1
• Sweat chloride test 1
• Immunoglobulin levels 1
• Mycobacterial cultures from sputum 1
• Consider whole-exome sequencing for extensive bronchiectasis with recurrent infections since childhood (to identify primary ciliary dyskinesia, primary immunodeficiency, atypical cystic fibrosis) 1

ABPM (Non-Aspergillus Allergic Bronchopulmonary Mycosis) Workup

If A. fumigatus-specific IgE is <0.35 kUA·L⁻¹ but clinical presentation suggests allergic bronchopulmonary mycosis, evaluate for ABPM. 1

• Requires repeated isolation of non-Aspergillus fungi (at least two sputum cultures or one BAL culture) 1
• Demonstrate sensitization to the implicated fungus (skin test or fungus-specific IgE) 1
• Serum total IgE ≥500 IU·mL⁻¹ 1
• Two of the following: blood eosinophil count ≥500 cells·μL⁻¹, fungus-specific IgG, fleeting chest radiographic opacities, or abnormal chest CT 1
• Absence of elevated IgE against rAsp f1, f2, and f4 strongly supports ABPM over ABPA 1