Eosinophilia

Essentials

• The normal circulating eosinophil count in adults is < 0.5 × 10⁹ /l. In infants less than one year old, the eosinophil count is higher, even up to 2.4 × 10⁹ /l.
• Blood eosinophilia is classified as mild (blood eosinophil count 0.5-1.5 × 10⁹ /l), moderate (1.5-5 × 10⁹ /l) or severe (> 5 × 10⁹ /l).
• If the blood eosinophil count repeatedly exceeds 1.5 × 10⁹ /l, the patient is said to have hypereosinophilia. Symptoms or organ damage associated with eosinophilia may sometimes occur even at lower levels.
  • Hypereosinophilia is classified into three groups depending on the underlying cause:
    • primary (clonal eosinophils related to a haematological disorder)
    • secondary (reactive/cytokine-mediated eosinophilia that is not clonal)
    • idiopathic hypereosinophilia (iHE, where the cause has not been identified).
  • In most cases, hypereosinophilia is either secondary or idiopathic. Clonal hypereosinophilia is rare. Clonal hypereosinophilia may be associated with chronic eosinophilic leukaemia (CEL) or other disease of the myeloid cell line, for example.
  • Hypereosinophilia may be asymptomatic. The blood eosinophil count is not proportional to the occurrence or severity of symptoms. Even severe hypereosinophilia may be asymptomatic, whereas even mild eosinophilia may be associated with symptoms or organ damage.
• Consider the following:
  • Could the eosinophilia be a sign of some underlying disease, which needs medical attention (based on history and status)?
  • Can the eosinophilia itself pose a threat to the patient (eosinophils can cause tissue damage through the proinflammatory cytokines secreted)?

Causes

Workup

• The assessment of eosinophilia requires a multifaceted approach.
• In mild eosinophilia without symptoms (blood eosinophil count 0.5-1.5 × 10⁹ /l) and with no evident secondary cause revealed by the patient history, it is usually sufficient to monitor the patient for any symptoms. Monitoring blood eosinophil counts every 1-3 months for any increase in eosinophilia is recommended if eosinophilia was detected recently and its cause is unknown.
• If eosinophilia is more pronounced and its cause is unknown, more thorough investigations are warranted. The patient's condition determines the urgency of further investigations. The investigation of obscure eosinophilias in symptomatic patients lies with a specialist. A specialist should also be consulted if an asymptomatic patient has severe hypereosinophilia (blood eosinophil count > 5 × 10⁹ /l).
• In the workup for hypereosinophilia, the following should be considered at the same time:
  • investigating symptoms / organ damage
  • investigating the aetiology.
• In the workup for hypereosinophilia, history and clinical examination play a key role. Targeted laboratory tests and imaging should be done as indicated case by case.
• When taking the history and performing the clinical examination, consideration should be given particularly to the underlying factors, symptoms and findings listed below.
  • Diagnosed chronic diseases
  • Previously diagnosed haematological or malignant diseases
  • Chronic infections and their risk factors (such as hepatitis, HIV, dental infections, foreign bodies)
  • Use of drugs, natural products and nutritional supplements
  • Travel history, living abroad (parasitic infections)
  • Bowel movements, faecal blood (infections, inflammatory bowel diseases, malignancies)
  • Respiratory symptoms, smoking (asthma, chronic obstructive pulmonary disease, vasculitides, malignancies)
  • Cardiac symptoms, arrhythmia
  • Skin, eye and mucosal symptoms, allergy symptoms (skin diseases, allergy, atopy)
  • Muscle and joint symptoms (rheumatic diseases), skeletal pain (malignancies)
  • Neurological symptoms
  • Lymph nodes, spleen size
  • In women, gynaecological symptoms, palpation of the breasts
  • In men, symptoms associated with the prostate
  • General symptoms: unintentional weight loss, atypical sweating or fatigue, slight fever
• Laboratory tests and imaging (carried out in a targeted fashion as indicated case by case)
  • Allergy, asthma and atopy tests, pulmonary function tests, IgE
  • Liver values, kidney values (including urine tests for haematuria and proteinuria)
  • Microbial samples (e.g. faecal parasites, anti-worm antibodies, HIV, hepatitis, Aspergillus)
  • Imaging (plain chest X-ray, as considered necessary: abdominal ultrasound examination, mammography, whole-body CT scan)
  • Sarcoidosis tests (ACE, lysozyme)
  • Vasculitis tests (ANCA antibodies, IgG4)
  • Morning cortisol level
  • Faecal calprotectin
  • Gastroscopy, colonoscopy
  • For investigation of possible cardiac involvement (e.g. endomyocarditis, thrombosis, endomyocardial fibrosis, valvular damage): troponin T, N-terminal-pro-BNP, ECG, echocardiography, MRI
  • Complete blood count with differential, serum tryptase, serum erythropoietin
• If there are signs of any haematological disorder, tests such as the following can be performed as considered necessary by a specialist.
  • JAK2 gene mutation and BCR-ABL fusion gene blood tests
  • Bone marrow aspirate or biopsy
    • PCR identification of FIP1L1-PDGFR alpha fusion gene resulting from deletion of 4q12 region
    • Testing for 5q33 region translocation (PDGFRB gene) and 8p11 translocation (FGRF1 gene) using either the G-band method or more sensitive FISH probes
    • T-cell receptor gene rearrangement test (TCR-D)
    • PCR identification of C-KIT gene mutation associated with mastocytosis
    • Flow-cytometric immunophenotyping
    • Fusion gene panel and myeloid mutation panel

Treatment

• Treatment of the underlying cause
• In severe eosinophilia, particularly if there are signs of organ damage (cardiac, neurological or thromboembolic) or there is rapidly progressing eosinophilia, the treatment for eosinophilia should be started immediately (in specialized care or consulting a specialist).
• First-line therapy is high-dose glucocorticoid: prednisolone 0.5-1.0 mg/kg/day or methylprednisolone 1 g/day.
• If the patient history reveals a stay in an endemic zone of Strongyloides stercoralis, empiric ivermectin therapy (Stromectol^® ) along with a glucocorticoid should be considered to prevent hyperinfection syndrome.
• In FIP1L1/PDGFRA positive forms of the disease, and sometimes in other forms too, the response to imatinib therapy or to other tyrosine kinase inhibitors may be favourable. In other cases, glucocorticoids or even cytotoxic agents may be considered.