eosinophilic lung disease
Contents
When asthma is accompanied by marked peripheral eosinophilia (> 1.5 × 10⁹/L), multisystem involvement, or treatment refractoriness — consider an “asthma-plus” syndrome. The differential includes ABPA, EGPA, AERD, hypereosinophilic syndrome, parasitic infection, and rarely lymphoproliferative disease.
when to suspect
- Blood eosinophils persistently > 1.5 × 10⁹/L
- Asthma refractory to standard therapy + systemic features (skin, sinus, neuropathy)
- Migratory pulmonary infiltrates
- New-onset asthma in an adult with eosinophilia
- Steroid-dependent asthma that relapses with dose reduction
classification
allergic bronchopulmonary aspergillosis (ABPA)
Hypersensitivity to Aspergillus fumigatus colonising the airways.
Diagnostic criteria (ISHAM 2024):
- Predisposition: asthma or cystic fibrosis
- Total IgE ≥ 500 IU/mL (obligatory — lowered from > 1000 in 2024 update)
- Demonstration of Aspergillus sensitisation (positive skin prick test or specific IgE)
- Plus ≥ 2 of the following:
- Aspergillus-specific IgG elevated
- Blood eosinophils ≥ 0.5 × 10⁹/L
- Suggestive CT imaging (central bronchiectasis ± high-attenuation mucous plugging — pathognomonic)
Management: systemic corticosteroids (initial 0.5 mg/kg prednisone, taper over 3–4 months) ± itraconazole (steroid-sparing; monitor levels). Omalizumab or dupilumab for steroid-dependent ABPA.
eosinophilic granulomatosis with polyangiitis (EGPA / Churg-Strauss)
Small-vessel vasculitis with eosinophilia, asthma, and multisystem involvement.
Classic triad: late-onset asthma + eosinophilia + vasculitis
Phases (may overlap):
- Allergic (asthma, rhinosinusitis)
- Eosinophilic (peripheral eosinophilia, pulmonary infiltrates)
- Vasculitic (neuropathy, purpura, cardiac, GI involvement)
Diagnosis:
- Blood eosinophils typically > 1.5 × 10⁹/L (often > 5.0)
- ANCA positive in ~40% (usually MPO/p-ANCA)
- Tissue biopsy: eosinophilic infiltration, necrotising vasculitis, granulomas
Red flags for EGPA in an asthma patient: mononeuritis multiplex, purpura, unexplained cardiomyopathy, eosinophilic GI disease, constitutional symptoms
Management: corticosteroids ± cyclophosphamide or mepolizumab / benralizumab (Fasenra) (both FDA-approved for EGPA). MANDARA (2024) demonstrated noninferiority of benralizumab to mepolizumab for remission induction.
Eosinophilic myocarditis is the leading cause of death. Cardiac MRI should be performed in all EGPA patients at diagnosis — ~45% of asymptomatic patients have abnormal cardiac findings. Do not wait for elevated troponin or overt cardiomyopathy.
hypereosinophilic syndrome (HES)
Sustained eosinophils > 1.5 × 10⁹/L with end-organ damage and no identifiable secondary cause.
- Overlap with EGPA when lung-predominant
- Exclude reactive causes (parasites, drugs, malignancy) and clonal causes (FIP1L1-PDGFRA fusion — check by FISH or molecular testing; found in ~10% of idiopathic eosinophilia)
- FIP1L1-PDGFRA-positive HES responds to imatinib
aspirin-exacerbated respiratory disease (AERD / Samter triad)
Triad: asthma + nasal polyposis + ASA/NSAID hypersensitivity
- Not IgE-mediated — it is a COX-1 inhibition-triggered overproduction of cysteinyl leukotrienes
- Typically develops in 20s–40s; worsening nasal congestion → polyps → aspirin reaction
- Diagnosis: clinical history ± aspirin provocation challenge (specialist setting)
- Management: aspirin avoidance, nasal polyposis surgery, ICS-LABA, LTRA (montelukast may help but variable), dupilumab (effective for both asthma and nasal polyps). Aspirin desensitisation is an option post-polypectomy in refractory disease
- Dupilumab may also increase aspirin tolerance — 57% of AERD patients developed increased tolerance (23% complete) after 6 months
parasitic eosinophilia — Strongyloides and others
- Strongyloides stercoralis — can cause eosinophilia and pulmonary infiltrates (Löffler syndrome). Chronic asymptomatic infection for decades. Hyperinfection if immunosuppressed (OCS, anti-IL-5 biologics)
- Other helminths: Ascaris, Toxocara, hookworm — consider with travel history
- Screen with serology in patients from endemic areas before starting OCS or anti-IL-5 therapy
T-cell lymphoma / lymphoproliferative disease
Rare but exam-relevant. Consider when:
- Peripheral eosinophilia is very high (> 5.0) with constitutional symptoms
- Hepatosplenomegaly, lymphadenopathy, skin lesions
- Poor response to corticosteroids
- Peripheral blood flow cytometry and bone marrow biopsy to evaluate
diagnostic workup — eosinophilic asthma-plus
| Investigation | Purpose |
|---|---|
| CBC with differential | Confirm eosinophilia; trend over time |
| Total IgE | Elevated in ABPA and allergic disease |
| Aspergillus specific IgE + IgG / skin prick | ABPA (2024 criteria require sensitisation + ≥ 2 supportive) |
| ANCA (MPO, PR3) | EGPA |
| CT chest | Central bronchiectasis (ABPA), infiltrates, ground glass |
| Strongyloides serology | Pre-biologic screening in at-risk populations |
| Urinalysis | Renal vasculitis (EGPA) |
| Troponin, ECG, cardiac MRI | Cardiac involvement (EGPA, HES) |
| Nerve conduction studies | Mononeuritis multiplex (EGPA) |
| Peripheral blood flow cytometry | Clonal eosinophilia / lymphoproliferative disease |
| FIP1L1-PDGFRA (FISH) | Myeloid HES — predicts imatinib response |
key distinguishing features
| Feature | ABPA | EGPA | AERD | HES |
|---|---|---|---|---|
| Asthma | Yes | Yes (late-onset) | Yes | Variable |
| Eosinophils | Moderate | Very high | Mild-moderate | Very high |
| IgE | ≥ 500 | Variable | Normal | Variable |
| ANCA | Negative | ~40% MPO+ | Negative | Negative |
| Nasal polyps | Uncommon | Common | Hallmark | Uncommon |
| Vasculitis features | No | Yes | No | Possible (organ damage) |
| Key investigation | Aspergillus IgE + IgG + CT | ANCA + biopsy | Clinical + ASA challenge | Flow cytometry + FISH |