Investigation of Churg-Strauss Syndrome in a Patient with Asthma and Possible ABPA
In a patient with asthma being investigated for ABPA who may have Churg-Strauss syndrome, you must first complete the ABPA diagnostic workup, then systematically evaluate for vasculitis features, as these conditions can coexist and require distinct treatment approaches.
Initial Diagnostic Priority: Rule Out or Confirm ABPA
The ABPA workup takes precedence because it shares overlapping features with Churg-Strauss syndrome (CSS), particularly asthma and eosinophilia, and must be systematically excluded or confirmed 1.
Essential ABPA Investigations
Serological Testing:
- A. fumigatus-specific IgE (must be ≥0.35 kUA·L⁻¹) 1
- Serum total IgE (must be ≥500 IU·mL⁻¹) 1
- A. fumigatus-specific IgG (using population-specific cut-offs or manufacturer recommendations) 1, 2
- Peripheral blood eosinophil count (≥500 cells·μL⁻¹) 1
Imaging:
- Thin-section chest CT (1.25-1.5 mm slices) at baseline to identify bronchiectasis, mucus plugging, and high-attenuation mucus (HAM) 1
Microbiological:
- Sputum fungal culture to identify species and guide therapy 1
Bronchoscopy Indications (Not Routine): Perform bronchoscopy only if 1:
- Diagnosis remains uncertain after initial workup
- Suspected ABPM with uninformative sputum cultures
- Unexplained hemoptysis
- Suspicion of tuberculous or non-tuberculous mycobacterial infection before initiating systemic glucocorticoids
Critical Caveat: Strongyloidiasis History
Before initiating any glucocorticoid therapy, you must exclude active strongyloidiasis, as immunosuppression can trigger hyperinfection syndrome with high mortality 1. This is particularly critical given the patient's history of possible previous strongyloidiasis.
Systematic Evaluation for Churg-Strauss Syndrome
Once ABPA workup is underway, simultaneously investigate for CSS features, as these conditions can coexist 3.
Clinical Features to Assess
Mandatory Features:
- Asthma (already present in this patient) 4, 5, 6
- Blood eosinophilia >1000/mm³ (or >10% of total WBC) 7, 5
Systemic Manifestations to Evaluate:
- Peripheral neuropathy (mononeuritis multiplex is highly specific) 7, 5, 6
- Paranasal sinusitis with nasal polyps 7, 5
- Pulmonary infiltrates on imaging (may overlap with ABPA findings) 7, 5
- Cardiac involvement (leading cause of CSS mortality - assess with ECG, troponin, BNP, echocardiography) 5, 6
- Skin manifestations (purpura, nodules) 5, 6
- Gastrointestinal symptoms (eosinophilic enteritis) 7
- Renal involvement (glomerulonephritis, though less common) 5
Essential Laboratory Investigations for CSS
Autoantibody Testing:
- Anti-neutrophil cytoplasmic antibodies (ANCA), specifically anti-MPO (myeloperoxidase) with perinuclear pattern (pANCA) 4, 5
Tissue Confirmation (When Feasible):
- Biopsy of affected organs showing eosinophilic inflammation, extravascular granulomas, and necrotizing vasculitis 4, 3, 6
- Nasal mucosa biopsy for granulomas 7
- Lung biopsy if diagnosis uncertain (may show both ABPA and CSS features) 3
American College of Rheumatology (ACR) Criteria for CSS
Diagnosis requires ≥4 of 6 criteria 7:
- Asthma
- Eosinophilia >10% on differential WBC count
- Mononeuropathy or polyneuropathy
- Pulmonary infiltrates (non-fixed, migratory)
- Paranasal sinus abnormality
- Biopsy showing extravascular eosinophils
Differential Diagnosis Considerations
Key Distinguishing Features:
The differential diagnosis is broad and requires systematic exclusion 1:
- ABPA alone: Elevated A. fumigatus-specific IgE and IgG, total IgE ≥500 IU·mL⁻¹, bronchiectasis, no systemic vasculitis features 1
- CSS alone: Systemic vasculitis features, ANCA positivity (in subset), extravascular granulomas, may have normal fungal serology 4, 5
- Combined ABPA and CSS: Both conditions can coexist, with CSS typically developing after ABPA 3
- Chronic eosinophilic pneumonia: Peripheral infiltrates, no vasculitis, no asthma history required 7
- Idiopathic hypereosinophilic syndrome: Eosinophilia without asthma or vasculitis 7, 4
- Severe asthma with fungal sensitization: Aspergillus sensitization without meeting ABPA criteria 1
Important Clinical Pitfall
Leukotriene receptor antagonist (LTRA) association: If the patient is taking montelukast or other LTRAs, CSS may be unmasked as oral glucocorticoids are withdrawn 7, 4. This represents either unmasking of pre-existing CSS or a potential pathogenic link 7.
Diagnostic Algorithm Summary
Step 1: Complete ABPA serological workup (A. fumigatus-specific IgE, total IgE, A. fumigatus-specific IgG, eosinophil count) 1
Step 2: Obtain thin-section chest CT and sputum fungal cultures 1
Step 3: Simultaneously assess for CSS systemic features (neuropathy, sinusitis, cardiac involvement, skin lesions) 5, 6
Step 4: Check ANCA (anti-MPO) 4, 5
Step 5: Exclude strongyloidiasis before any immunosuppression 1
Step 6: Consider tissue biopsy if diagnosis remains uncertain or if both conditions suspected 3
Step 7: Apply ACR criteria for CSS (≥4 of 6) and ISHAM-AWG criteria for ABPA 1, 7
Additional Workup for Bronchiectasis Etiology
Since both ABPA and CSS can cause bronchiectasis, and patients may have additional underlying causes, perform 1:
- Complete blood count
- Sweat chloride test (to exclude cystic fibrosis)
- Immunoglobulin levels (IgG, IgA, IgM subclasses)
- Mycobacterial cultures from sputum
- Consider whole-exome sequencing if extensive bronchiectasis with recurrent infections since childhood
This systematic approach ensures accurate diagnosis of either ABPA alone, CSS alone, or the rare combination of both conditions, while avoiding the critical error of initiating immunosuppression in the presence of undiagnosed strongyloidiasis 1, 3.