Eosinophilia – Causes, Symptoms, Diagnosis, Treatment

Eosinophilia – Causes, Symptoms, Diagnosis, Treatment

Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.5×109/l (500/μL). Eosinophils usually account for less than 7% of the circulating leukocytes. A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia.[rx] Several causes are known, with the most common being some form of an allergic reaction or parasitic infection.

Eosinophils are a kind of blood granulocytes that express cytoplasmic granules that contain basic proteins and bind with acidic dyes like “eosin.” They derive from bone marrow, and IL-5, IL-3, and GM-CSF stimulate their production. They have a circulating half-life of 4.5 to 8 hours. They can reside in tissues, mostly in the respiratory tract, gastrointestinal tract, for 8 to 12 days. Eosinophils are less than 5% of circulating leucocytes. Eosinophilia is defined as an increase of circulating eosinophils >500 /mm^3.

Based on the counts, eosinophilia can subdivide into different categories: mild (500 and 1500/mm^3), moderate (150 to 5000/mm3), and severe (>5000/mm^3). Hypereosinophilic syndrome is defined as an absolute eosinophil count greater than 1500/mm3 on two occasions at least one month apart or marked tissue eosinophilia.

Peripheral eosinophilia is characterized as
  • Mild: 500 to 1500/mcL (0.5 to 1.5 × 109/L)
  • Moderate: 1500 to 5000/mcL (1.5 to 5 × 109/L)
  • Severe: > 5000/mcL (> 5 × 109/L)


Eosinophils become differentiated in bone marrow, and once they leave the marrow, they stop maturing further. They reside in tissues, mostly outside the vasculature. In eosinophil related disorders, eosinophils are recruited into the involved tissues. T helper-2 cells mediated immune responses and IL-5 production induce eosinophilopoiesis and eosinophil activation. The major cytokine responsible for eosinophil production and activation is IL-5 [9,10]. After activation, eosinophils degranulate and release the cationic proteins into the tissues through which eosinophils perform their functions. These released proteins can be proteolytic enzymes, which can cause damage to the host wall as well. Eosinophil also releases cytokines, like IL-10 and IL-14, which aid in maintaining homeostasis and immunoregulation.

Causes of Eosinophilia

Eosinophilia can be primary or secondary:

Primary causes
  • Chronic eosinophilic leukemia
  • Myeloid and lymphoid neoplasms with rearrangements of with PDGFRA, PDGFRAB or FGFR1 genes
  • Hereditary eosinophilia
  • Idiopathic hypereosinophilic syndrome 
Secondary causes
  • Parasitic infestations: ancylostomiasis, ascariasis, cysticercosis, echinococcosis (hydatid cyst), schistosomiasis, strongyloidiasis, trichinellosis, visceral larva migrans (toxocariasis)
  • Fungal and bacterial infections: bronchopulmonary aspergillosis, chronic tuberculosis (occasionally), coccidioidomycosis, disseminated histoplasmosis, scarlet fever
  • Allergic disorders: bronchial asthma, hay fever, Stevens-Johnson syndrome, drug, and food allergic reactions, DRESS syndrome
  • Skin diseases: Atopic dermatitis, eczema, pemphigus, Mycosis fungoides, Sezary syndrome
  • Graft versus host reaction
  • Connective tissue disease: Chrug-Strauss syndrome, eosinophilia myalgia syndrome
  • Miscellaneous: reactive pulmonary eosinophilia, tropical eosinophilia, pancreatitis, eosinophilic gastroenteritis

Eosinophilia can be idiopathic (primary) or, more commonly, secondary to another disease.[rx][rx] In the Western World, allergic or atopic diseases are the most common causes, especially those of the respiratory or integumentary systems. In the developing world, parasites are the most common cause. A parasitic infection of nearly any bodily tissue can cause eosinophilia. Diseases that feature eosinophilia as a sign include:

  • Allergic disorders
    • Asthma
    • Hay fever[rx]
    • Drug allergies[rx]
    • Allergic skin diseases
      • Pemphigus
      • Dermatitis herpetiformis
  • IgG4-related disease
  • Parasitic infections[rx]
  • Addison’s disease and stress-induced suppression of adrenal gland function[rx]
  • Some forms of malignancy
    • Acute lymphoblastic leukemia
    • Chronic myelogenous leukemia
    • Eosinophilic leukemia
    • Clonal eosinophilia[rx]
    • Hodgkin lymphoma[rx]
    • Some forms of non-Hodgkin lymphoma[rx]
    • Lymphocyte-variant hypereosinophilia
    • Systemic mastocytosis
  • Systemic autoimmune diseases[rx]
    • Systemic lupus erythematosus
    • Kimura disease[rx]
    • Eosinophilic granulomatosis with polyangiitis[rx]
    • Eosinophilic fasciitis[rx]
    • Eosinophilic myositis
  • Eosinophilic myocarditis[rx]
  • Eosinophilic esophagitis[rx]
  • Eosinophilic gastroenteritis[rx]
  • Cholesterol embolism (transiently)[rx]
  • Coccidioidomycosis (Valley fever), a fungal disease prominent in the US Southwest.[rx]
  • Human immunodeficiency virus infection
  • Interstitial nephropathy
  • Hyperimmunoglobulin E syndrome, an immune disorder characterized by high levels of serum IgE
  • Idiopathic hypereosinophilic syndrome.[rx]
  • Congenital disorders
    • Hyperimmunoglobulin E syndrome[rx]
    • Omenn syndrome[rx]
    • Familial eosinophilia[rx]
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Symptoms of Eosinophilia

Normally your blood doesn’t have a large number of eosinophils. Your body may produce more of them in response to

  • Allergic disorders
  • Skin conditions
  • Parasitic and fungal infections
  • Autoimmune diseases
  • Some cancers
  • Bone marrow disorders

Diagnosis of Eosinophilia


An eosinophil is around 12 to 17 µm in diameter and has a segmented nucleus. It has abundant cytoplasmic granules that contain proteolytic enzymes. Four major proteins comprise the granules: major basic protein (MBP1), eosinophilic cationic protein (ECP), eosinophil derived neurotoxin (EDN) and eosinophil peroxidase (EOP). They stain red-orange with Romanowsky stains.

History and Physical

Due to the heterogeneous manifestations of the disease and severity varying from mild to end-organ damage, comprehensive history taking and diligent physical examination is extremely important, and sometimes enough, for diagnosis. Skin, pulmonary, and gastrointestinal organ systems are commonly involved. Constitutional symptoms like low-grade fevers, night sweats, fatigue, weight loss can occur in multiple conditions, including myeloproliferative and lymphoid neoplasms, Churg Strauss syndrome, DRESS syndrome.

Skin rashes, pruritus can be seen in cutaneous T cell lymphoma, eczema. Dyspnea, cough, wheezing can be seen in multiple conditions, including bronchopulmonary aspergillosis, Loeffler’s syndrome, hay fever, asthma, reactive pulmonary eosinophilia, Churg strass syndrome. Detailed travel history, work environment, drug history, close contacts with HIV, syphilis helps identify infections, parasitic infestations, and drug adverse reactions. Physical examination should be complete, including a skin assessment, lung auscultation to look for rhonchi, wheezes, abdomen exam to look for splenomegaly.

  • Diagnosis is by complete blood count (CBC) – However, in some cases, a more accurate absolute eosinophil count may be needed.[rx][rx]
  • Specific test – for causative conditions are performed, often including chest x-ray, urinalysis, liver and kidney function tests, and serologic tests for parasitic and connective tissue diseases.
  • The stool – is often examined for traces of parasites (i.e. eggs, larvae, etc.) though a negative test does not rule out parasitic infection; for example, trichinosis requires a muscle biopsy.[rx]
  • Elevated serum B12 or low white blood cell  – alkaline phosphatase, or leukocytic abnormalities in a peripheral smear indicates a disorder of myeloproliferation.[rx] In cases of idiopathic eosinophilia, the patient is followed for complications. A brief trial of corticosteroids can be diagnostic for allergic causes, as the eosinophilia should resolve with suppression of the immune over-response.[rx]
  • Marrow aspiration and biopsy – Neoplastic disorders are diagnosed through the usual methods, such as bone marrow aspiration and biopsy for the leukemias, MRI/CT to look for solid tumors, and tests for serum LDH and other tumor markers.[rx]
  • The evaluation for primary eosinophilia – should begin with screening peripheral blood for FIP1L1- PDGFRA gene fusion. Diagnostic testing should start with a peripheral smear. Cytogenetic testing and FISH analysis can be performed on peripheral blood as well.
  • Concurrent cytophilic or cytopenias – if present, can help for diagnosis. In that case, bone marrow biopsy, along with karyotype and genetic screen of chromosomes, may be required.
  • B12 level and tryptase level – along with cytogenetic/immunophenotypic testing and marrow findings, help diagnose chronic mastocytosis, acute/chronic myeloid leukemia, myelodysplastic syndrome, MDS/MPN overlap. When skin rashes are present, skin biopsy helps to diagnose cutaneous disorders like pemphigoid, eczema, mycosis fungoides, Sezary syndrome. Imaging of the chest helps diagnose aspergillosis, Loeffler syndrome, Churg Strauss syndrome. An ultrasound abdomen helps to evaluate for splenomegaly. Stool testing helps to assess for parasitic infections.
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Treatment of Eosinophilia

Management depends on the underlying cause. The goal of the therapy is to mitigate end-organ damage from eosinophilia. In mild cases without any symptoms or signs of organ involvement, a conservative approach can be undertaken. In emergency conditions with hemodynamic instability or organ failure, treatment with IV steroids is important.

For some conditions like drug and food allergies or infections, treatment can be simple, like withdrawing the offending agent or treating with antibiotics. But in some conditions, due to the varying clinical manifestations and multi-systemic involvement, a multidisciplinary approach involving hematologist, pulmonologist, infectious diseases, might be necessary. In steroid-resistant cases of hypereosinophilic syndrome and chronic eosinophilic leukemia, hydroxyurea and interferon-alpha have demonstrated efficacy.

In aggressive forms of the disease, second-line cytotoxic agents and stem cell transplants have proven some benefit. Antibody use against interleukin-5 (IL-5) (mepolizumab), the IL-5 receptor (benralizumab), and CD52 (alemtuzumab), as well as other targets on eosinophils, continues to be an active area of investigation. Timely intervention is vital to reduce morbidity and mortality.

Treatment is directed toward the underlying cause.[rx] However, in primary eosinophilia, or if the eosinophil count must be lowered, corticosteroids such as prednisone may be used. However, immune suppression, the mechanism of action of corticosteroids, can be fatal in patients with parasitosis.[rx]


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