What are the causes of eosinophilia?

Causes of Eosinophilia

Eosinophilia is most commonly caused by allergic disorders (approximately 80% of cases), followed by parasitic infections, with additional causes including immunologic disorders, malignancies, and drug reactions. 1

Primary Classification of Causes

1. Secondary (Reactive) Causes

• Allergic/Atopic Disorders (most common overall cause)

  • Allergic asthma
  • Food allergies
  • Atopic dermatitis
  • Drug reactions
  • Hay fever

• Infectious Causes

  • Parasitic infections (most common identifiable cause in returning travelers/migrants)
    • Helminths:
      • Strongyloides stercoralis (can persist lifelong and cause hyperinfection syndrome)
      • Schistosomiasis (associated with bladder carcinoma)
      • Onchocerciasis
      • Filariasis
      • Hookworm infections
      • Ascariasis
      • Trichuriasis
    • Fungal infections:
      • Coccidioidomycosis
      • Paracoccidioidomycosis
      • Aspergillosis (allergic bronchopulmonary)

• Immunologic/Inflammatory Disorders

  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
  • Other systemic vasculitides
  • Immunodeficiency syndromes:
    • Hyperimmunoglobulin E syndrome (Job syndrome)
    • Omenn syndrome
    • Wiskott-Aldrich syndrome

• Malignancies

  • Solid tumors (especially advanced stage)
  • Lymphoid malignancies (particularly T-cell lymphomas)
  • Hodgkin lymphoma

• Dermatologic Conditions

  • Atopic dermatitis
  • Urticaria
  • Eczema

2. Primary (Neoplastic) Causes

• Myeloid/Lymphoid Neoplasms with Eosinophilia and TK Fusion Genes

  • FIP1L1-PDGFRA fusion gene (commonly associated with endomyocardial thrombosis and fibrosis)
  • Other tyrosine kinase fusion genes

• Other Myeloid Malignancies

  • Chronic myeloid leukemia (CML)
  • Acute myeloid leukemia (AML)
  • Advanced systemic mastocytosis (SM)

• Idiopathic Hypereosinophilia

  • When no cause can be identified despite thorough investigation

Clinical Manifestations of Eosinophilia

Organ damage can occur due to increased production and/or persistent accumulation of eosinophils in tissues, regardless of the underlying cause. The most commonly affected organ systems include:

• Skin: Rash, urticaria, pruritus
• Lungs: Cough, dyspnea, bronchospasm
• Gastrointestinal tract: Abdominal pain, diarrhea
• Heart: Endomyocardial fibrosis, thrombosis (particularly with FIP1L1-PDGFRA fusion gene)
• Nervous system: Neuropathy, encephalopathy

Diagnostic Approach

1. Confirm eosinophilia: Peripheral blood eosinophil count >0.5 × 10⁹/L

2. Assess severity:

   • Mild: 0.5-1.5 × 10⁹/L
   • Moderate to severe: >1.5 × 10⁹/L (higher risk of organ damage)

3. Evaluate for end-organ damage:

   • Cardiac evaluation (ECG, echocardiogram)
   • Pulmonary assessment
   • Neurologic examination

4. Investigate potential causes:

   • Travel history (especially to tropical regions)
   • Medication review
   • Allergy history
   • Specific testing based on clinical suspicion:
     • Stool examination for parasites
     • Serologic testing for helminths
     • Skin testing for allergies
     • Bone marrow examination and genetic testing for suspected neoplastic causes

Important Clinical Considerations

• Persistent eosinophilia ≥1.5 × 10⁹/L for more than 3 months requires hematology referral after infectious causes have been excluded or treated 1
• Eosinophilia with evidence of end-organ damage requires urgent medical assessment 1
• Many helminth infections do not cause eosinophilia, so normal eosinophil counts do not exclude parasitic infection 2
• In travelers returning from tropical regions, helminth infections are the most common identifiable cause of eosinophilia 1, 2
• The absence of peripheral eosinophilia does not exclude tissue eosinophilia or eosinophil-mediated organ damage 1

Remember that accurate diagnosis of the underlying cause of eosinophilia is essential to establish the appropriate treatment plan and prevent potential complications such as endomyocardial fibrosis, thromboembolism, and other organ damage.