What is the appropriate management for a patient with hypotransferrinemia and eosinophilia?

Management of Low Transferrin with High Absolute Eosinophils

The combination of hypotransferrinemia and eosinophilia requires immediate investigation for genetic transferrin defects while simultaneously pursuing a comprehensive workup for the eosinophilia, as these are likely two separate pathologic processes that demand distinct management strategies.

Addressing the Hypotransferrinemia

Diagnostic Approach

• Consider genetic hypotransferrinemia in patients presenting with unexplained hypochromic microcytic anemia, low iron binding capacity (low serum transferrin concentrations), and increased ferritin concentrations 1
• Mutation analysis of the TF gene is recommended to confirm the diagnosis 1
• Homozygous or compound heterozygous TF defects confirm the diagnosis of hypotransferrinemia due to a TF defect 1

Treatment for Hypotransferrinemia

• Transferrin supplementation by either plasma transfusion or apotransferrin infusion is recommended as the primary treatment 1
• Iron status must be monitored closely to detect toxic iron loading early, as this is a significant complication 1
• If systemic iron loading develops, phlebotomies are recommended as first-line therapy 1
• If phlebotomies are not tolerated due to decreasing hemoglobin, chelation therapy should be initiated 1

Addressing the Eosinophilia

Immediate Risk Assessment

• Any eosinophilia with evidence of end-organ damage requires urgent medical evaluation and consideration of emergency treatment 2
• Cardiac symptoms (chest pain, dyspnea, heart failure, arrhythmias), pulmonary symptoms (persistent cough, wheezing, infiltrates), or neurological symptoms (altered mental status, focal deficits, peripheral neuropathy) demand immediate assessment 2
• Absolute eosinophil count ≥1.5 × 10⁹/L persisting for more than 3 months or exceeding 5.0 × 10⁹/L at any time carries significant risk of morbidity and mortality 2

Diagnostic Workup for Eosinophilia

Priority 1: Exclude Helminth Infections (Most Common Cause)

• Obtain detailed travel history focusing on geographic areas visited, freshwater exposure, and timing of exposure 3
• Perform concentrated stool microscopy for all patients 3
• Strongyloides serology is recommended due to high diagnostic yield across all regions, as this parasite can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients 3, 2
• Schistosomiasis serology if freshwater exposure in endemic areas (Africa) 3
• Consider empirical treatment with albendazole 400 mg plus ivermectin 200 μg/kg as single doses for asymptomatic eosinophilia in patients aged >24 months with suspected helminth infection 3

Priority 2: Evaluate for Allergic/Atopic Disorders

• Allergic/atopic disorders constitute approximately 80% of cases of secondary reactive eosinophilia 3
• Assess for asthma, food allergies, and atopic dermatitis 3
• Review medications for common culprits: non-steroidal anti-inflammatory drugs, beta-lactam antibiotics, and nitrofurantoin 3

Priority 3: Screen for Clonal/Hematologic Disorders

• If eosinophilia persists ≥1.5 × 10⁹/L for more than 3 months with no identified cause after infectious workup and treatment, referral to hematology is mandatory 3, 2
• Hematology evaluation should include morphologic review of blood and marrow, standard cytogenetics, fluorescence in situ-hybridization, flow immunophenotyping, and T-cell clonality assessment 4
• Molecular testing for PDGFRA, PDGFRB, FGFR1, or PCM1-JAK2 rearrangements is critical, as these predict response to imatinib 4

Treatment Based on Eosinophilia Etiology

For Helminth-Related Eosinophilia:

• Albendazole 400 mg as a single dose for hookworm infection 3
• Monitor eosinophil counts after treatment to confirm resolution 3

For Clonal Eosinophilia:

• Imatinib for patients with PDGFRA or PDGFRB rearrangements (exquisite responsiveness) 4
• Corticosteroids as first-line for lymphocyte-variant hypereosinophilia and idiopathic HES 4
• Hydroxyurea and interferon-alfa for steroid-refractory cases 4

For Mild Eosinophilia (<1.5 × 10⁹/L) Without Organ Involvement:

• Watch and wait approach with close follow-up may be appropriate 4

Critical Pitfalls to Avoid

• Do not assume normal eosinophil counts exclude helminth infection, as many infected patients have normal counts 3, 2
• Do not delay investigation of persistent moderate-to-severe eosinophilia, as end-organ damage can be subclinical initially 2
• Serological tests for helminths may not become positive until 4-12 weeks after infection 3
• Stool microscopy may be negative during the tissue migration phase when eosinophilia is present 3
• In immunocompromised patients, urgent evaluation for Strongyloides is mandatory due to high mortality risk of hyperinfection syndrome 2

Monitoring Strategy

• Serial iron studies and ferritin levels to detect iron overload in hypotransferrinemia patients 1
• Serial eosinophil counts to assess treatment response 3
• Cardiac evaluation (ECG, echocardiography, troponin) if eosinophilia is moderate-to-severe or persistent, as myocarditis and endomyocardial fibrosis are life-threatening complications 3, 2
• Pulmonary function testing and chest imaging if respiratory symptoms present 2