Eosinophilia: Symptoms, Causes, Diagnosis and Treatment

Eosinophilia is a complex hematological disorder characterized by the abnormal increase in eosinophils in the blood. It is associated with various conditions such as allergies, parasites, drug reactions, and hematological malignancies. This article provides comprehensive scientific information on the diagnosis, symptoms, and causes of eosinophilia, combining modern conventional therapies (corticosteroids, biologics) with functional approaches to correct the body's radical imbalances, offering a complete therapeutic framework.

What is eosinophilia

Eosinophilia is the increase in eosinophils in peripheral blood above 500 cells per microliter of blood. Eosinophils are a key element of the immune system and are mainly involved in allergic reactions and defense against parasitic infections. The presence of elevated eosinophils is not a diagnosis but is indicative of an underlying disease. Eosinophilia is divided into mild (500-1500/μL), moderate (1500-5000/μL), and severe (>5000/μL). Proper history analysis, clinical examination, and laboratory tests are critical to finding the cause.

Epidemiological data

The incidence of eosinophilia varies internationally. In developed countries, it occurs in about 0.1-0.3% of the general population, while in areas with endemic parasites (e.g., sub-Saharan Africa, India), the rates are higher. Eosinophilic esophagitis (EoE), a chronic eosinophilic disorder, has shown increasing trends over the past two decades, with a global estimated incidence of 1-5 per 10.000 population. According to recent studies in Greece, eosinophilia is mainly associated with allergic diseases and, to a lesser extent, with parasites, due to the high level of hygiene and medical care.

Symptoms

The clinical picture of eosinophilia varies significantly depending on the level and location of eosinophilic infiltration. It is often asymptomatic and is detected randomly in a blood test. When symptoms are present, these may include:

Respiratory system: chronic cough, shortness of breath, wheezing, and recurrent pneumonia.
Skin manifestations: rashes, redness, urticaria, and severe itching.
Gastrointestinal system: nausea, vomiting, abdominal pain, diarrhea, or malabsorption of food.
Cardiovascular complications: eosinophilic myocarditis, pericarditis, which can be life-threatening.
Neurological symptoms: neuropathies, muscle weakness, or sensory disorders.

The severity of symptoms is often related to the duration and degree of eosinophilia.

Causes

Eosinophilia can be the result of a variety of factors and is classified into:
Primary causes
They are characterized by a neoplastic disorder of hematopoietic cells (e.g., chronic eosinophilic leukemia).
Secondary (reactive) causes

Allergies: allergic rhinitis, asthma, food allergies.
Parasites: mainly helminth infections.
Drug reactions: antibiotics, NSAIDs, antiepileptics.
Autoimmune diseases: sarcoidosis, Churg-Strauss syndrome.

Idiopathic hypereosinophilic syndromes (HES)
Chronic disorder of unknown etiology with localized or systemic infiltration by eosinophils.
Identifying the cause is the basis for proper treatment.

Deeper Causes of Eosinophilia

The functional medical approach focuses on finding and addressing eosinophilia's underlying causes, not just suppressing the symptoms. The leading recognized causes include:

Dysbiosis and leaky gut (Leaky Gut)
Damage to the intestinal barrier leads to increased permeability, transit of endotoxins, and immune system activation through Th2 lymphocytes. Fasano, A. (2012). Leaky gut and autoimmune diseases. Clinical Reviews in Allergy & Immunology, 42(1), 71-78.

Chronic latent infections
Microorganisms such as Candida, Blastocystis, and Giardia can cause chronic inflammation and disruption of immune homeostasis. Yason, J.A. et al. (2021). Gut dysbiosis and eosinophilic gastrointestinal disorders. Frontiers in Immunology, 12, 752931.

Food intolerances
Chronic reactions to foods such as gluten, soy, and dairy can activate eosinophils. Lucendo, A.J. (2017). Eosinophilic esophagitis and food hypersensitivity. United European Gastroenterology Journal, 5(5), 698-707.

Chronic exposure to toxins
Heavy metals and endocrine disruptors can cause oxidative stress and an increased eosinophilic response. Valko, M. et al. (2005). Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chemico-Biological Interactions, 160(1), 1-40.

Adrenal dysfunction
Chronic activation of the hypothalamic-pituitary-adrenal axis can weaken immune regulation. Tsigos, C., Chrousos, G.P. (2002). Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. Journal of Psychosomatic Research, 53(4), 865-871.

Nutritional deficiencies
Vitamin D, zinc, and selenium deficiency have been associated with an increased risk of chronic inflammation. Gombart, A.F. et al. (2020). A review of micronutrients and the immune system. Nutrients, 12(1), 236.

Genetic predisposition
Some polymorphisms lead to overproduction of IL-5 and other pro-eosinophilic cytokines. Rosenberg, H.F. et al. (2013). Eosinophils and their disorders: genetic aspects. Immunological Reviews, 252(1), 152–163.

Pathophysiology

The pathophysiology of eosinophilia is complex and involves the oversecretion and action of cytokines, mainly interleukin-5 (IL-5), the main growth factor of eosinophils. IL-5 is produced mainly by Th2-type T-lymphocytes and eosinophils in a self-reinforcing cycle.

Other important cytokines and factors involved are IL-3, GM-CSF, and eotaxin, which attract eosinophils to tissues. In primary syndromes, such as chronic eosinophilic leukemia, clonal abnormalities and genetic mutations, such as FIP1L1-PDGFRA gene fusion, are observed.

Tissue infiltration by eosinophils causes inflammation and damage through the release of cellular granules containing:

Major Basic Protein (MBP)
Eosinophilic cationic protein (ECP)
Eosinophilic Peroxidase (EPO)

These proteins are cytotoxic to tissue cells.

Diagnosis

The diagnosis of eosinophilia is based on the systematic approach:

History and clinical examination: to identify a possible cause (e.g., medications, allergies, travel).
General blood count (CBC): the key marker is the absolute number of eosinophils.
Immunological tests: IgE, ANA, RF to check for autoimmune or allergic causes.
Parasitological tests, especially in cases of travel or endemic areas.
Imaging methods: chest X-ray and CT scan in case of suspected tissue infiltration.
Tissue biopsy is used in complex cases where confirmation of tissue infiltration by eosinophils is required.

The combination of these tests is necessary to reveal the underlying cause.

Differential diagnosis

Differential diagnosis of eosinophilia is critical for proper patient management. The main situations to be excluded include:

Infections: mainly parasitic, such as infections with Ascaris, Toxocara, and Schistosoma.
Allergic disorders, such as allergic rhinitis, asthma, and atopic dermatitis.
Drug reactions: especially to antibiotics, antiepileptics, and NSAIDs.
Hematological malignancies: acute and chronic myeloid leukemia, lymphohyperplastic syndromes;
Autoimmune syndromes, such as Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis).
Idiopathic hypereosinophilic syndromes (HES): diagnosed after all of the above have been ruled out.

The use of diagnostic approach algorithms can significantly help in effective diagnosis.

Therapy

The therapeutic approach to eosinophilia depends on the cause and severity of the condition:
1. Causal treatment

Antiparasitic treatment for parasitic infections.
Treatment of drug reactions involves the discontinuation of the responsible drugs.
Treatment of allergic diseases with antiallergic drugs and immunotherapy.

2. Symptomatic treatment

Corticosteroids (e.g., prednisolone) are considered the first-line treatment for most forms of eosinophilia, and their levels are immediately reduced.
Biologics: Recent treatments with monoclonal antibodies, such as mepolizumab, benralizumab, and reslizumab, which target IL-5, offer solutions for resistant cases.
Immunosuppressants, such as interferon-α or hydroxyurea, for severe forms of HES.

Therapeutic Approaches in Functional Medicine

Functional medicine offers a holistic and personalized treatment strategy for eosinophilia. Unlike classical medicine, which focuses on managing symptoms (e.g., the increase in eosinophils), the functional approach aims to identify and correct the underlying causes of the body's inflammatory response.

Restoration of the intestinal microbiome
Gut health is considered the foundation of immune balance. Dysbiosis, which involves the imbalance of friendly and pathogenic microbes, has been linked to chronic inflammation and activation of eosinophils.
Treatment includes:

The administration of probiotics (Lactobacillus, Bifidobacterium) and prebiotic fibers is necessary to strengthen the intestinal barrier.
Remove irritating foods by excluding potential allergens (e.g., gluten, soy, dairy).
Supplements such as L-glutamine, zinc carnosine, and quercetin help heal the intestinal wall (de Meij et al., 2018).

Eradication of chronic infections
Parasites, Candida, H. pylori, or other dysbiotic infections constantly stimulate the immune system. Functional medicine applies natural antimicrobials such as berberine, oregano extract, and garlic allicin, always under careful guidance (Slavin, 2013).

Detoxification
Eliminating toxic loads such as heavy metals, pesticides, and endocrine disruptors is essential. Antioxidant supplements (N-acetylcysteine, glutathione, vitamin C) support liver and kidney function (Pizzorno, 2014).

Adjusting the HPA Axis and Managing Stress
Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is often associated with allergic sensitivities and chronic inflammation.

Adaptogens such as Ashwagandha and Rhodiola can stabilize the stress response.
Anti-inflammatory diet (Mediterranean diet with fresh fruits, vegetables, omega-3s) (Lopresti, 2019).

Micronutrient restoration
Vitamin D, zinc, selenium, and magnesium deficiency affect immune homeostasis. Proper supplementation is a key part of treatment (Gombart et al., 2020).

Prognosis

The prognosis of eosinophilia directly depends on the cause and severity of tissue damage.

Patients with secondary eosinophilia due to allergies or parasitic infections usually have an excellent prognosis, with full recovery after appropriate treatment.
Patients with idiopathic hypereosinophilic syndromes (HES) may have a chronic course of flare-ups and remissions, requiring long-term monitoring.
The prognosis of patients with eosinophilic leukemia depends on response to treatment and genetic abnormalities.

The development of biologic therapies has significantly improved patient outcomes and quality of life. Future research focuses on new molecular targets and optimization of immunotherapy.

Conclusions

Eosinophilia is a complex clinical phenomenon with many causes and manifestations. The right diagnostic approach and personalized treatment can avoid serious complications. Advances in molecular biology and the development of biological agents have opened up new horizons in treating the disease. Continuous research and cooperation between the various specialties remain key to optimal patient care.

Frequently Asked Questions (FAQs)

What are eosinophils?
Eosinophils (or eosinophils) are a type of white blood cell that participates in defense against parasites and allergens.

When is their increase considered pathological?
When their number in the blood exceeds 500 cells/μL.

Is eosinophilia dangerous?
It can be, especially if it causes tissue damage (e.g., heart, lungs).

How is it treated?
Removing the cause (e.g., medications, infections) and medication (corticosteroids, biologics).

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