What is the appropriate evaluation and management approach for a patient presenting with eosinophilia and weakness?

Evaluation and Management of Eosinophilia with Weakness

For a patient presenting with eosinophilia and weakness, immediately assess for end-organ damage (cardiac, pulmonary, neurologic) and obtain urgent hematology consultation if the absolute eosinophil count is ≥1.5 × 10⁹/L, as weakness is a cardinal symptom of myeloid/lymphoid neoplasms with tyrosine kinase fusion genes and hypereosinophilic syndrome, both of which carry significant mortality risk without prompt treatment. 1, 2

Immediate Red Flag Assessment

Weakness with eosinophilia demands urgent evaluation for life-threatening organ damage:

• Cardiac involvement must be ruled out immediately—obtain ECG, cardiac troponin, and NT-proBNP in all patients, as endomyocardial thrombosis and fibrosis are common in primary eosinophilic disorders and can present with weakness, chest pain, dyspnea, or heart failure 1, 2
• Neurologic involvement requires urgent assessment—weakness may indicate eosinophil-induced peripheral neuropathy or CNS involvement; obtain electromyography if motor or sensory deficits are present 2
• Pulmonary involvement should be evaluated with chest X-ray and pulmonary function tests if respiratory symptoms accompany weakness 2

Severity-Based Triage

The absolute eosinophil count determines urgency:

• ≥5.0 × 10⁹/L at any time requires immediate hematology referral regardless of symptoms 2
• ≥1.5 × 10⁹/L persisting >3 months requires hematology referral after infectious causes excluded 2, 3
• 0.5-1.5 × 10⁹/L warrants investigation for secondary causes, particularly helminth infections in travelers 2

Systematic Diagnostic Approach

Step 1: Rule Out Secondary Causes (Most Common)

Obtain detailed travel history focusing on:

• Fresh water exposure in Africa/tropical regions (schistosomiasis risk) 2
• Raw/undercooked meat consumption (trichinellosis, which classically presents with severe myalgia and muscle weakness) 1, 2
• Timing of travel relative to symptom onset 2

Helminth infections account for 19-80% of eosinophilia in returning travelers and must be excluded first:

• Send three separate concentrated stool specimens for ova and parasites 1, 2
• Obtain Strongyloides serology and culture immediately—this parasite can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients 1, 2
• Send schistosomiasis serology if fresh water exposure in endemic areas 2

Critical warning for Loa loa: Do not use diethylcarbamazine if microfilariae are seen on blood film, as it may cause fatal encephalopathy; use corticosteroids with albendazole first to reduce microfilarial load to <1000/ml before definitive treatment 2

Other secondary causes to evaluate:

• Medication review (drug reactions are common) 1
• Allergic disorders (most common cause in non-endemic areas, occurring in ~80% of cases) 1
• Solid tumors and lymphoid malignancies (Hodgkin lymphoma, T-cell lymphomas) 1

Step 2: Evaluate for Primary Eosinophilic Disorders

If secondary causes excluded and eosinophils ≥1.5 × 10⁹/L, obtain:

• Complete blood count with differential—look for neutrophilia, basophilia, thrombocytosis, monocytosis, myeloid immaturity, dysplasia, anemia, thrombocytopenia, or increased blasts 1
• Peripheral blood smear and bone marrow biopsy with morphologic review 3
• Cytogenetic testing: standard karyotype and FISH for PDGFRA, PDGFRB, FGFR1, and PCM1-JAK2 rearrangements 1, 3
• Next-generation sequencing gene assays 3
• Flow immunophenotyping 3
• T-cell clonality assessment to detect lymphocyte-variant hypereosinophilia 3

Identification of PDGFRA or PDGFRB rearrangements is critical because these diseases respond exquisitely to imatinib 3

Step 3: Document End-Organ Damage

Systematic organ assessment is mandatory:

Cardiac (most critical):

• Echocardiography if troponin elevated or clinical features suggest cardiac injury 2
• Cardiac MRI to distinguish eosinophilic cardiac disease from other etiologies 2

Pulmonary:

• Chest X-ray to identify infiltrates 2
• Bronchoscopy with bronchoalveolar lavage if imaging suggests parenchymal disease 2

Neurologic:

• EMG to confirm eosinophil-induced peripheral neuropathy 2
• Nerve biopsy if EMG findings consistent with neuropathy 2

Gastrointestinal:

• Endoscopy with multiple biopsies (minimum 6: 2-3 proximal, 2-3 distal esophagus) if dysphagia present 2

Dermatologic:

• Deep skin biopsy including fascia if cutaneous involvement suspected 2

Treatment Algorithm

For Myeloid/Lymphoid Neoplasms with PDGFRA/PDGFRB Rearrangements:

• Imatinib is first-line therapy due to exquisite responsiveness 3

For Lymphocyte-Variant Hypereosinophilia or Idiopathic HES:

• Corticosteroids are first-line therapy 3
• Hydroxyurea and interferon-α for steroid-refractory cases 3
• Mepolizumab (anti-IL-5 antibody) is FDA-approved for idiopathic HES 3

For Helminth Infections:

• Strongyloidiasis: Ivermectin 200 μg/kg daily for 2 days 2
• Trichinellosis (presents with severe myalgia/weakness): Albendazole 400 mg daily for 8-14 days in severe disease 1
• Schistosomiasis: Praziquantel 40 mg/kg single dose, repeated at 6-8 weeks; add prednisolone 20 mg/day for 5 days in acute Katayama syndrome 2

For Eosinophilic Esophagitis (if dysphagia present):

• Topical swallowed corticosteroids (fluticasone or budesonide) are first-line 1
• Maintenance therapy mandatory after achieving remission due to high relapse rates 1

Monitoring Strategy

For patients with eosinophilia <1.5 × 10⁹/L without organ involvement:

• Watch and wait approach with close follow-up 3

For treated patients:

• Regular clinic visits to assess for development of symptoms or end-organ damage 2
• Repeat endoscopy with biopsies if gastrointestinal symptoms recur during treatment 1
• Monitor for treatment-related complications (corticosteroid side effects, imatinib hepatotoxicity) 1

Critical Pitfalls to Avoid

• Do not assume normal eosinophil counts exclude helminth infection—many infected patients have normal counts 2
• Do not delay parasitic workup before starting corticosteroids—obtain three stool specimens and Strongyloides serology immediately, as corticosteroids can precipitate fatal hyperinfection syndrome in undiagnosed strongyloidiasis 2
• Do not wait for symptoms to develop before investigating persistent moderate-to-severe eosinophilia—end-organ damage can be subclinical initially 2
• Do not rely solely on peripheral eosinophil counts to assess tissue eosinophilia—tissue biopsy is the gold standard 2