Eosinophilic Leukocytosis- An Overview

Introduction:

Eosinophilic leukocytosis is caused by numerous medical conditions such as allergic infections, cancers, and auto-immune diseases. Frequent exposure to parasites, allergic pollutants, and adverse drug reactions are the main reasons for the occurrence of eosinophilic leukocytosis. Medications such as antiepileptic agents, antibiotics, and allopurinol are some of the common drugs that result in eosinophilic leukocytosis. Careful evaluation and close monitoring for any allergic responses after starting new drugs would help in minimizing severe complications.

What Are Eosinophils?

Eosinophils are a sub-group of white blood cells (leukocytes). They are secreted as an immune response to allergic stimuli, infections causing allergies (parasitic and fungal), skin reactions, autoimmune disorders, and certain bone marrow diseases (also in some cancers). Eosinophils belong to granulocytic leukocytes that are produced in the bone marrow and commonly circulate in the connective tissues such as the thymus, spleen, lymph nodes, gastrointestinal tract, uterus, and ovaries.

Eosinophils help to fight infections by increasing inflammatory response in the body. In normal circumstances, their levels are relatively low in circulation, which accounts for about one to 4 % of the total circulating white blood cells. More eosinophils are released during allergic reactions or infections and are activated. These eosinophils reach the triggering site and induce inflammatory reactions. They release free radicals and toxic proteins to fight microorganisms (parasitic infections). Chemical mediators such as prostaglandins, leukotrienes, and cytokines are released during eosinophilic activation.

What Is Eosinophilic Leukocytosis?

High levels of eosinophils in blood circulation are termed eosinophilic leukocytosis. It is a collective term describing an immune-mediated response that occurs due to diverse inflammatory triggering factors and is not related to any particular disease. The triggering factors include allergic, infectious, and neoplastic disorders. In excessive levels of circulating eosinophils (eosinophilia), these eosinophils migrate outside the bloodstream (extravascularly) and get deposited in the tissues and organs leading to cellular damage. The various types of eosinophilic leukocytosis depending on the triggering factors and resulting clinical features are as follows -

• Transient Eosinophilic Leukocytosis - usually occurs as acute allergic responses such as exposure to allergens and mild drug reactions.

• Reactive Eosinophilic Leukocytosis - is seen during parasitic infections and toxic drug-induced immune responses.

• Secondary Eosinophilic Leukocytosis - occurs in organ-related eosinophilia and malignancies.

• Idiopathic Eosinophilic Leukocytosis - .occurs due to an unknown cause.

• Familial Eosinophilic Leukocytosis - occurs due to hereditary causes.

• Asymptomatic Eosinophilic Leukocytosis - here elevated levels of eosinophils are seen in blood but do not show clinical manifestations.

What Causes Eosinophilic Leukocytosis?

High levels of eosinophils (eosinophilic leukocytosis) are caused by diverse conditions such as allergic responses, infections, immunological disorders, etc. some of the causes of eosinophilic leukocytosis are as follows -

Factors Triggering Allergic Responses Triggering Allergic Responses:

• Asthma.

• Dermatitis (skin reactions)

• Allergic rhinitis.

• Metal-induced allergens (iridium, mercury, nickel).

• Chemicals (solvents like trichloroethylene).

• Drug reactions (sulfonamide drugs, anticonvulsants, antibiotics).

• Herbal preparations and medications.

• Atopic dermatitis (eczema and dryness of the skin).

• Hypersensitivity reactions.

Infections:

• Parasitic (helminths like Trichuris trichura).

• Allergic bronchopulmonary aspergillosis (fungal infections).

• HIV-1(seen as secondary eosinophilia).

Eosinophilic Syndromes Due to Skin Hypersensitivity Reactions:

• Atopic dermatitis.

• Recurrent granulomatous dermatitis (eosinophilic cellulitis).

• Angioedema.

• Urticaria (elevated itchy rash).

• Pemphigoid (fluid-filled blisters).

Secondary Eosinophilic Leukocytosis Involving Organs:

• Lung involvement (eosinophilic pneumonia).

• Eosinophilic endomyocardial fibrosis.

• Eosinophilic esophagitis (gastrointestinal disorders).

• Eosinophilic granulomatosis associated with polyangiitis.

• Eosinophilic meningitis.

• Eosinophilic fasciitis.

• Eosinophilic cystitis (renal inflammation).

Eosinophilic Leukocytosis Associated With Neoplastic Changes:

• Hodgkin’s disease.

• Myeloid neoplasms.

• Chronic eosinophilic leukemia.

• Lymphoid neoplasms.

• Systemic mastocytosis associated with eosinophilia.

• Chronic myelogenous leukemia.

Miscellaneous Causes:

• Hyperimmunoglobulin E syndrome.

• Adrenal insufficiency.

• Hereditary (familial hypereosinophilia, autosomal dominant familial eosinophilia).

• Idiopathic or unknown causes.

What Are the Clinical Manifestations of Eosinophilic Leukocytosis?

The signs and symptoms of eosinophilic leukocytosis vary according to the triggering factors and underlying disease state. The severity also follows a diverse pattern from asymptomatic individuals to severe complications. The clinical presentation of various forms of eosinophils leukocytosis include -

• Transient Eosinophilic Condition - usually seen in acute reactive processes like asthma and allergic rhinitis.

• About 40% of patients with asthma exacerbations need hospitalization.

• Benign Drug-Induced Reactions - occurs after 6 to 12 days of drug exposure (penicillin, sulfonamide drugs, etc.).

• Eosinophilic leukemoid-like reactions are seen in anticonvulsant drugs.

• Persistent chronic infections are reported in parasitic infections in endemic areas.

• Helminth infection is the most common cause of moderately occurring eosinophilia.

• Cardiovascular symptoms develop in chronic eosinophilic degranulation that occurs intravascularly.

• Eosinophilic granules that are released damage the endocardial tissue.

• Prolonged and recurrent endocardial damage causes endomyocardial fibrosis.

• The damaged endocardium also favors thrombus formation resulting in stroke and vascular occlusions.

• Eosinophilic cardiomyopathy.

• Chest pain and shortness of breath.

• Diarrhea (eosinophilic colitis).

• Difficulty in swallowing (eosinophilic esophagitis).

• Cough associated with shortness of breath (eosinophilic pneumonia).

• In eosinophilic granulomatosis associated with polyangiitis, asthma occurs along with inflammation in the blood vessels resulting in vasculitis.

• Drug rashes.

• DRESS Syndrome (Drug Reactions With Eosinophilia and Systemic Symptoms) - extensive and painful skin rashes occur associated with lymphadenopathy and organ involvement.

• Unusually, the syndrome occurs after two to eight weeks of drug administration.

• Antiepileptic medications are the most common cause of drug-induced eosinophilic leukocytosis.

• Drug rashes, fever, and multiple organ failure (lungs, kidneys) are frequently reported.

• In asymptomatic cases, mild eosinophilia is seen in the blood with no noticeable clinical symptoms.

What Is the Diagnosis of Eosinophilic Leukocytosis?

Careful evaluation of eosinophilic leukocytosis is essential to identify the underlying causes. A complete blood count (CBC) forms the first line of screening tests to detect increased eosinophil count. Detailed clinical examination and laboratory investigations help in the differential diagnosis of eosinophilic leukocytosis. The diagnostics of eosinophilic leukocytosis are as follows -

• The absolute eosinophil count (AEC) indicates the number of eosinophils circulating in the blood.

• The number of eosinophils is estimated by counting the stained eosinophils per 100 white blood cells (WBCs) multiplied by the total WBC count.

• Eosinophils show clumped chromatin and segmented nuclei and appear as large brightly colored red cytoplasmic granules under the Giemsa-wright staining method.

• An absolute eosinophil count (AEC) with a clinical value of more than 450 cells/μL is indicative of eosinophilic leukocytosis.

• AEC more than 1500/μL is suggestive of hypereosinophilic syndrome and eosinophil count above 1500 cells/μL causes end-organ damage.

• In the case of the hypereosinophilic syndrome, persistently high levels of eosinophils are seen for a minimum of six months.

• Examination of bone marrow aspirate and biopsy is done to differentiate malignant conditions (leukemia) from non-malignant causes.

• Increased levels of immunoglobulin E (IgE) confirm the presence of allergic reactions and parasitic infections.

• Conventional cytogenetic studies help to rule out secondary and neoplastic causes.

• Fluorescent in situ hybridization (FISH).

• Flow cytometry including T-cell receptor analysis.

• Pulmonary function tests and chest CT (computed tomography) scans are done to assess the involvement of the lungs.

• Echocardiographic studies help to rule out cardiac involvement.

• Stool examination and serological testing are done to identify parasitic infections.

How to Treat Eosinophilic Leukocytosis?

The treatment for eosinophilic leukocytosis depends on the severity of eosinophilia. However, patients with recurrent hypereosinophilia are prone to tissue damage. The heart and lungs are the two vulnerable organs and require immediate intervention to prevent end-organ damage.

• In mild cases, the removal of allergens reduces the eosinophilic count. Patients should be advised not to be exposed to allergic stimuli.

• Allergic suppression greatly responds to treatment by glucocorticosteroids.

• In hypersensitivity reactions, the eosinophil count drastically reduces within hours of starting steroid treatment.

• An empirical treatment regime with anti-helminthic agents reduces parasitic infections.

• Baseline assessment of lung function tests and cardiac function studies are regularly monitored to assess treatment prognosis.

Conclusion:

Multiple disorders and disease processes lead to eosinophilic leukocytosis. A detailed examination and elaborate laboratory investigations are needed to identify the underlying causes. Treatment interventions include the reduction of eosinophils levels and prevent organ damage. Nevertheless, eosinophilic leukocytosis plays a vital role as a hematologic marker that serves as a clue for various related disorders.