Eosinophilia

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Eosinophilia is an elevation of eosinophils in the peripheral circulation (absolute count > 500/mm³). Eosinophilia can be primary (e.g., due to a hematologic disorder), secondary (e.g., due to infection or inflammation), or idiopathic. Diagnosis involves a detailed history and examination and studies such as CBC with differential, a peripheral blood smear (PBS), and inflammatory markers. Additional studies to assess for tissue hypereosinophilia, secondary causes, and end-organ damage are chosen based on clinical presentation and suspected cause. Management is based on the underlying cause.

• Eosinophilia: an elevation in the number of eosinophils in the peripheral circulation, usually considered an absolute eosinophil count (AEC) > 500/mm³ and/or eosinophil differential > 5% ^[2][3][4]
  • Mild: 500–1,500/mm^{3 [3][4]}
  • Moderate: 1,500–5,000/mm^{3 [3][4]}
  • Severe: > 5,000/mm^{3 [3][4]}
• Hypereosinophilia: a moderate to severe elevation in the number of eosinophils in the peripheral circulation with an AEC of ≥ 1,500/mm^{3 [2][5]}
• Tissue hypereosinophilia: a histopathologic finding of extensive tissue infiltration by eosinophils ^[3]

The following list includes common and/or significant causes of eosinophilia. It is not exhaustive. ^[2][6]

• Allergic conditions
  • Allergic rhinitis
  • Asthma
• Medications
  • Medications that cause drug hypersensitivity reactions (e.g., DRESS)
  • Interleukin-2 therapy
• Dermatologic conditions
  • Atopic dermatitis
  • Eczema
  • Dermatitis herpetiformis ^[7]
  • Erythema multiforme ^[8]
  • Bullous pemphigoid ^[7]
• Infections
  • Parasitic (e.g., strongyloidiasis, ascariasis, scabies)
  • Fungal; (e.g., aspergillosis, coccidioidomycosis, histoplasmosis)
  • Bacterial (e.g., scarlet fever, leprosy, genitourinary infections, chlamydial infections) ^[8][9]
  • Viral (e.g., HIV, HTLV-1) ^[7]
  • Protozoan (e.g., isosporiasis)
• Neoplastic disorders
  • Solid tumors (e.g., lung cancer, colorectal adenocarcinoma) ^[7]
  • Leukemia (e.g., CML, AML)
  • Lymphoma (e.g., Hodgkin lymphoma, non-Hodgkin lymphomas)
  • T-cell lymphoproliferative disorders
• Myeloproliferative neoplasms ^[9]
  • Polycythemia vera
  • Myelofibrosis
• Gastrointestinal disorders
  • Inflammatory bowel disease
  • Chronic pancreatitis
  • Celiac disease
  • Eosinophilic esophagitis
• Rheumatologic
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Eosinophilic fasciitis
• Pulmonary syndromes
  • Sarcoidosis
  • Allergic bronchopulmonary aspergillosis
  • Löffler syndrome
• Vasculitis
  • Eosinophilic granulomatosis with polyangiitis
  • Polyarteritis nodosa
• Other
  • Cholesterol embolization syndrome
  • Primary adrenal insufficiency
  • Radiation exposure
  • Chronic graft-versus-host disease
  • Solid organ transplant rejection ^[7]
  • Hyper-IgE syndrome
  • IgG4-related disease
  • Omenn syndrome

Focused history ^[2]

• Constitutional symptoms (e.g., fever, night sweats, weight loss, pruritus)
• History of atopy
• Detailed medication list
• Detailed travel history

Focused physical examination ^[2][6]

• Skin changes (rash, erythema)
• Signs of infection
• Signs of malignancy, e.g.:
  • Lymphadenopathy
  • Splenomegaly
  • Hepatomegaly

Approach ^[2]

• Confirm the diagnosis.
  • CBC and/or PBS to measure AEC
  • Histopathology of tissue and/or bone marrow aspirate to assess for tissue hypereosinophilia
• Review prior results to determine chronicity.
• Obtain further studies (e.g., allergens testing) in patients with clinical manifestations suggesting a specific cause and with persistent moderate to severe eosinophilia.
• Patients with AEC ≥ 1,500/mm³: Consider evaluating for hypereosinophilic syndrome.

Initial studies ^[2][6]

Obtain initial studies in all patients.

• CBC with differential
  • Assess for leukocytosis and eosinophilia.
  • Concurrent RBC and platelet abnormalities suggest a myeloproliferative disorder.
• PBS
  • Verify accurate eosinophil count.
  • Assess for underlying causes (e.g., parasites, dysplastic cells suggestive of malignancy).
• ESR and CRP: elevated in inflammatory conditions or reactive processes
• LDH: elevated in hematologic conditions, neoplastic conditions, and tissue injury
• CMP: elevated renal and/or liver functions in reactive processes or hypereosinophilic syndrome
• Vitamin B₁₂ assay: elevated in myeloid disorders

Further studies ^[2][10]

Further evaluation is based on the clinical presentation and initial studies and may include the following:

• Allergic conditions: diagnostics for type I hypersensitivity reactions (e.g., skin prick test)
• Dermatologic conditions: skin biopsy
• Infections
  • Parasite testing (e.g., stool microscopy, serologic tests)
  • Viral studies (e.g., HIV testing, EBV viral load)
  • Fungal studies (e.g., aspergillosis testing)
• Inflammatory conditions: serologies (e.g., ANA, ANCA)
• Hematologic or neoplastic conditions
  • Molecular or cytogenetic testing and/or flow cytometry on peripheral blood or bone marrow, e.g.:
    • Peripheral blood analysis for FIP1L1-PDGFRA
    • Testing for other gene mutations (e.g., BCR-ABL or mutations on JAK2 or PDGFRB)
    • Lymphocyte phenotyping (e.g., staining for CD3, CD19, CD8)
  • Tissue biopsy
  • Imaging (e.g., CXR, CT, or bone scan to identify malignancy)
  • Serum tryptase: elevated in myeloid disorders and systemic mastocytosis
• Gastrointestinal conditions
  • EGD and/or colonoscopy with biopsy
  • Tissue transglutaminase antibodies to assess for celiac disease
• Respiratory disease
  • Imaging (e.g., CXR, CT)
  • Bronchoscopy with biopsy
• Cardiovascular disease
  • Serum troponin
  • Echocardiogram
  • Cardiac MRI if serum troponin and/or echocardiogram is abnormal

Management is based on the underlying cause. Treatment of hypereosinophilic syndrome is discussed separately.

• Definition: a group of rare conditions characterized by persistent elevations in AEC ≥ 1,500/mm³ in peripheral circulation with eosinophil tissue infiltration and resultant end-organ damage ^[2][3]
• Epidemiology: Prevalence is estimated to be 0.3–6.3 per 100,000 inhabitants. ^[23]
• Etiology
  • Primary (neoplastic): caused by an underlying myeloid, stem cell, or eosinophil neoplasm that produces clones of malignant eosinophils; often found with variant genes such as PDGFRA and PDGFRB
  • Secondary (reactive): caused by an underlying condition (e.g., infection, inflammatory process)
  • Familial (e.g., Omenn syndrome)
  • Idiopathic
• Clinical features ^[3]
  • Evidence of end-organ damage (most commonly to the lungs, heart, gastrointestinal system, skin, and/or nervous system), e.g.:
    • Dyspnea
    • Chest pain
    • Leg edema
    • Severe abdominal pain
    • Nausea and vomiting
    • Rashes or blisters
    • Neurologic deficits
  • Thromboembolic phenomena
• Diagnostics ^[3][6][10]
  • Absolute eosinophil count ≥ 1,500/mm³ on measurements taken 2–4 weeks apart ^[3]
  • ↑ Serum tryptase
  • Tyrosine kinase mutations (e.g., FIP1L1-PDGFRA) or other genetic mutations
  • Tissue or bone marrow biopsy ^[3]
    • > 20% eosinophils in bone marrow
    • Significant tissue infiltration of eosinophils or deposition of eosinophil granules
• Treatment: in consultation with a specialist, e.g., hematology
  • Patients with life-threatening end-organ damage , AEC ≥ 100,000/mm³, or rapidly rising AEC ^[2][10]
    • Stabilize patients and provide immediate hemodynamic support.
    • Initiate corticosteroids, e.g., methylprednisolone (off-label) . ^[2]
    • Administer ivermectin empirically if potential exposure to Strongyloides.
  • Primary: chemotherapy based on mutation (e.g., imatinib in FIP1L1-PDGFRA) or other hematologic neoplasm (e.g., AML)
  • Idiopathic
    • Corticosteroids are first-line.
    • Additional medications (e.g., imatinib, interferon alpha, mepolizumab) may be considered based on response to initial treatment.