Eosinophilia: Symptoms, Types, Causes and Treatment

Eosinophilia is a condition defined by an elevated number of eosinophils—a type of white blood cell—in the blood or tissues. Eosinophils play crucial roles in immune responses, particularly in allergic reactions and defense against parasitic infections. However, an increased eosinophil count can signal a range of health issues, from benign allergies to life-threatening disorders. Understanding eosinophilia’s symptoms, types, causes, and available treatments is essential for both patients and healthcare providers.

Symptoms of Eosinophilia

Eosinophilia often remains asymptomatic, especially when mild. When symptoms do arise, they vary widely depending on the underlying cause and the organs affected. Recognizing these symptoms is vital for early diagnosis and appropriate management.

Symptom	Description	Organ/System	Source(s)
Rash	Skin eruptions, often with itching or swelling	Skin	5 9
Abdominal pain	Discomfort, cramping, nausea	Gastrointestinal	2 10
Dysphagia	Difficulty swallowing	Esophagus	1 3 19
Cough/Wheezing	Persistent cough, breathing difficulty	Respiratory	16 18
Fever	Elevated body temperature	Systemic	4 5
Fatigue	Unusual tiredness or weakness	Systemic	4 5
Lymphadenopathy	Swollen lymph nodes	Immune/Lymphatic	5
Myalgias	Muscle aches	Musculoskeletal	4

Table 1: Key Symptoms

Common Presentations

Eosinophilia’s symptoms are often subtle and overlooked, but certain patterns help guide diagnosis:

• Skin Symptoms: Many eosinophilic disorders present with skin manifestations like rashes, urticaria (hives), or swelling. Some rare forms, such as eosinophilic cellulitis and fasciitis, cause deeper tissue involvement, leading to swelling, plate-like hardness, or pain in the limbs 4 9.
• Gastrointestinal Symptoms: Disorders like eosinophilic esophagitis (EoE) manifest as difficulty swallowing (dysphagia), vomiting, abdominal pain, or food impaction. In children, emesis and abdominal pain predominate, while adults more often experience dysphagia 1 2 3 19.
• Respiratory Symptoms: Cough, wheezing, and shortness of breath can signal eosinophil involvement in the lungs, as seen in asthma or certain drug reactions 16 18.
• Systemic Symptoms: Fever, fatigue, and lymphadenopathy (swollen lymph nodes) can occur, especially in systemic eosinophilic syndromes like DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) or hypereosinophilic syndrome (HES) 5 11 12.
• Other Symptoms: In severe cases, organ-specific symptoms appear—such as heart involvement in hypereosinophilic syndrome, or kidney and liver dysfunction in DRESS 5 11 12.

Organ-Specific Manifestations

Skin and Soft Tissue

• Eosinophilic dermatoses: Rashes, blisters, or nodules.
• Eosinophilic fasciitis: Symmetrical swelling, hardness, and pain, usually in the limbs 4 9.

Gastrointestinal Tract

• Eosinophilic esophagitis: Dysphagia, food impaction.
• Eosinophilic gastroenteritis/colitis: Abdominal pain, diarrhea, vomiting 1 2 10.

Respiratory Tract

• Asthma with eosinophilic inflammation: Wheezing, cough, breathlessness 16 18.

Systemic Involvement

• Hypereosinophilic syndrome: Involvement of heart, lungs, skin, nerves; can be life-threatening 11 12.
• DRESS syndrome: Rash, lymphadenopathy, fever, and organ dysfunction—commonly liver, kidneys, lungs 5.

Key Points

• Symptoms are highly variable and depend on the cause and affected organs.
• Many patients are asymptomatic, especially with mild eosinophilia.
• Severe or persistent symptoms require thorough investigation for underlying disease.

Types of Eosinophilia

Understanding the classification of eosinophilia is essential for targeted diagnosis and management. Eosinophilia is generally classified by etiology and, sometimes, by severity or tissue involvement.

Type	Defining Feature	Typical Causes	Source(s)
Secondary	Reactive to another condition	Allergies, infections, drugs	6 7 8 12
Clonal	Associated with a hematologic malignancy	Myeloid neoplasms, leukemias	6 7 11 12
Idiopathic	No identifiable underlying cause	Diagnosis of exclusion	6 7 11 12
Hypereosinophilic Syndrome (HES)	Persistent high eosinophils + organ damage	Any (often idiopathic)	6 11 12
Tissue	Eosinophils accumulate in specific tissues	Skin, GI tract, lungs	8 9 10

Table 2: Types of Eosinophilia

Classification Overview

Secondary (Reactive) Eosinophilia

• Cause: Increased eosinophils due to another disease process.
• Common Triggers: Parasitic/helminthic infections (especially in travelers), allergic disorders (asthma, eczema), drug reactions, autoimmune diseases, certain lymphomas 6 7 8 12 13.
• Mechanism: Usually driven by cytokines (mainly IL-5) produced by T-cells 8 17.

Clonal (Primary) Eosinophilia

• Cause: Eosinophils are part of a malignant clone in hematologic cancers.
• Diseases: Chronic eosinophilic leukemia, myeloid/lymphoid neoplasms with specific gene mutations (e.g., PDGFRα, PDGFRβ), systemic mastocytosis 6 7 11 12.
• Diagnostic Clues: Cytogenetic or molecular evidence of malignancy; often requires bone marrow biopsy 7 11 12.

Idiopathic Eosinophilia

• Definition: Elevated eosinophils with no identifiable secondary or clonal cause.
• Diagnosis: By exclusion after thorough evaluation 6 7 11 12.

Hypereosinophilic Syndrome (HES)

• Definition: Persistent eosinophilia (≥1.5 x 10⁹/L for ≥6 months, or shorter if severe) with organ involvement, not explained by other causes 6 11 12.
• Variants: Lymphocytic (secondary) and myeloproliferative (primary) forms exist 11.

Tissue Eosinophilia

• Definition: Eosinophil accumulation in specific tissues, sometimes with or without blood eosinophilia 8 9 10.
• Examples: Eosinophilic esophagitis (esophagus), eosinophilic fasciitis (fascia), eosinophilic dermatoses (skin), eosinophilic pneumonia (lungs) 1 3 4 9 10.

How Types Guide Management

• Secondary: Treat the underlying condition (e.g., infection, allergy).
• Clonal: Disease-specific therapies, sometimes targeted at mutations.
• Idiopathic/HES: Immunosuppression (e.g., corticosteroids), with organ protection a priority.
• Tissue: Local and systemic therapies depending on severity and location.

Causes of Eosinophilia

Eosinophilia can result from a wide range of conditions, making a systematic approach to diagnosis essential. The causes differ by geography, patient demographics, and clinical context.

Cause Category	Examples	Distinctive Features	Source(s)
Infections	Helminths, protozoa	Common in travelers, migrants	7 8 13
Allergic Diseases	Asthma, atopic dermatitis, urticaria	Common in developed countries	7 8 9 16
Drugs	Antibiotics, anticonvulsants (e.g., DRESS)	Rash, systemic symptoms	5 7 8 11
Autoimmune/Inflamm.	Vasculitis, connective tissue diseases	Systemic features	7 8 9
Malignancy	Lymphoma, myeloid neoplasms	Clonal eosinophilia	7 8 11 12
Primary Immunodef.	Wiskott-Aldrich, Omenn syndrome, CVID	Often severe, syndromic	14
Idiopathic	Hypereosinophilic syndrome	Diagnosis of exclusion	6 7 11 12

Table 3: Causes of Eosinophilia

Infectious Causes

• Parasitic Infections: The leading cause globally, especially in regions with poor sanitation or among travelers. Helminths (worms) like Strongyloides, Schistosoma, and Toxocara frequently cause marked eosinophilia 7 8 13.
• Other Infections: Some fungal and protozoal infections.

Allergic/Atopic Disorders

• Asthma, Allergic Rhinitis, Atopic Dermatitis: Allergic diseases are common triggers, especially in developed regions 7 8 9 16 18.
• Eosinophilic Dermatoses: Urticaria, eczema, bullous pemphigoid, and other skin conditions feature eosinophil-rich inflammation 9.

Drug Reactions

• DRESS Syndrome: Severe drug reaction with eosinophilia and systemic symptoms, frequently involving rash, lymphadenopathy, fever, and organ dysfunction. Common culprits include some antibiotics and anticonvulsants 5 7 8 11.
• Other Drug Eruptions: Allergic reactions to various medications.

Autoimmune and Inflammatory Diseases

• Vasculitis: Such as Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis).
• Other Connective Tissue Diseases: Can feature tissue and blood eosinophilia 7 8 9.

Malignancies

• Lymphomas: Especially T-cell lymphomas can drive eosinophil production 7 8 11 12.
• Myeloid Neoplasms: Chronic eosinophilic leukemia, systemic mastocytosis, and other disorders with clonal eosinophil expansion 11 12.

Primary Immunodeficiencies

• A growing list of syndromes, including Wiskott-Aldrich, Omenn syndrome, common variable immunodeficiency (CVID), and others, have been linked to eosinophilia—sometimes severe 14.

Idiopathic (Unknown Causes)

• When all other causes are excluded, the diagnosis is idiopathic eosinophilia or hypereosinophilic syndrome (HES) 6 7 11 12.

Special Considerations

• Geographic Factors: Infections are more common in resource-poor settings; allergies and autoimmune causes dominate in developed countries 7 13.
• Age and Context: Drug reactions and allergies are more common in adults; parasitic infections and immunodeficiencies in children.

Treatment of Eosinophilia

The management of eosinophilia centers on treating the underlying cause, preventing organ damage, and, in some cases, directly reducing eosinophil counts. Treatment strategies have advanced significantly, particularly for severe or refractory cases.

Approach	Main Interventions	Indications	Source(s)
Treat Underlying Cause	Antiparasitics, antibiotics, allergen avoidance	Secondary eosinophilia	7 13
Immunosuppression	Corticosteroids, immunosuppressants	HES, severe allergy, tissue	1 3 5 11 12
Biologics	Anti-IL-5 (mepolizumab, reslizumab), anti-IL-5Rα (benralizumab), anti-IL-13 (QAX576)	Refractory or severe disease	15 16 17 18
Dietary Therapy	Elimination diets, amino acid formulas	Eosinophilic GI diseases	1 19
Endoscopic Dilation	Mechanical dilation of narrowed esophagus	EoE with strictures	3 19
Targeted Chemotherapy	Imatinib, other TKIs	Clonal eosinophilia	11 12

Table 4: Main Treatment Approaches

Treating the Underlying Cause

• Infections: Antiparasitic drugs are highly effective; proper diagnosis (stool microscopy, serology) is critical for migrants or travelers 7 13.
• Allergic/Atopic Disorders: Allergen avoidance, topical steroids, antihistamines, and in some cases, immunotherapy 7 8 9.
• Drug Reactions: Immediate cessation of the offending drug; corticosteroids for severe presentations like DRESS 5.

Immunosuppressive Therapy

• Corticosteroids: First-line for hypereosinophilic syndrome, severe tissue eosinophilia, or organ-threatening disease. They rapidly lower eosinophil counts and control symptoms, but relapse is common upon withdrawal 1 3 5 11 12.
• Other Immunosuppressants: Used when steroids are ineffective or contraindicated.

Targeted Biologic Therapies

• Anti-IL-5 Agents: Mepolizumab and reslizumab block IL-5, a key cytokine in eosinophil survival and activation. These agents are approved for eosinophilic asthma and show benefit in HES and other eosinophilic disorders 16 17 18.
• Anti-IL-5Rα: Benralizumab targets the eosinophil surface receptor, leading to direct cell lysis 17 18.
• Anti-IL-13: QAX576 showed promise in eosinophilic esophagitis, reducing tissue eosinophil counts and improving symptoms 15.
• Indications: Biologics are used for patients with severe, refractory, or steroid-dependent disease.

Dietary and Local Therapies

• Dietary Elimination: Removing food antigens (e.g., milk, wheat, soy, eggs, nuts, seafood) is highly effective in eosinophilic esophagitis and gastroenteritis. Elemental diets (amino acid-based formulas) are reserved for severe cases or young children 1 19.
• Topical Steroids: Swallowed inhaled steroids (fluticasone, budesonide) are effective for eosinophilic esophagitis 1 3 19.

Mechanical/Procedural Interventions

• Endoscopic Dilation: Used for esophageal strictures in EoE when medical therapy cannot restore normal swallowing 3 19.

Targeted Chemotherapy

• Imatinib and Similar Agents: Used for clonal eosinophilia with specific mutations (e.g., PDGFRα, PDGFRβ). These therapies are highly effective in appropriate patients 11 12.

Monitoring and Follow-Up

• Assessment: Regular blood counts, organ function tests, and, in some cases, tissue biopsies (e.g., repeat endoscopy in EoE) 19.
• Long-Term Management: Individualized based on disease severity, response to therapy, and risk of relapse.

Conclusion

Eosinophilia is a complex condition with varied presentations and causes, ranging from benign allergies to serious systemic diseases. Early recognition and targeted therapy can prevent complications and improve quality of life. Key points include:

• Symptoms are diverse, depending on the underlying disease and affected organs.
• Classification is essential for guiding diagnostic work-up and treatment—distinguishing between secondary, clonal, idiopathic, and tissue-specific forms.
• Causes are broad, including infections, allergies, drugs, autoimmune diseases, malignancies, immunodeficiencies, and unknown (idiopathic) factors.
• Treatment focuses on underlying causes, with advanced therapies available for severe or refractory cases, including biologics and targeted drugs.
• Multidisciplinary care and regular monitoring are crucial for optimal outcomes, especially in severe or multi-organ disease.

Summary of Main Points:

• Eosinophilia symptoms range from skin rashes to life-threatening organ damage.
• Types include secondary (reactive), clonal (malignant), idiopathic, and tissue-specific eosinophilia.
• Causes span infections, allergies, drugs, autoimmune diseases, cancers, and immunodeficiencies.
• Treatment is tailored to the cause; new biologics and targeted therapies offer hope for severe cases.

By understanding these aspects, patients and clinicians can work together for timely diagnosis and management, minimizing the risk of complications from this often-overlooked but important blood abnormality.