Eosinophilia Causes and Clinical Manifestations

Introduction to Eosinophilia

• The American College of Physicians suggests that the primary causes of eosinophilia include allergic disorders (80% of cases), parasitic infections (the second most common cause), hematological and solid neoplasias, drug reactions, autoimmune diseases, and hypereosinophilic syndromes 1, 2, 3

Causas Infecciosas

• Infections with intestinal helminths, such as Anquilostomas (Ancylostoma duodenale, Necator americanus), Ascaris lumbricoides, and Strongyloides stercoralis, are associated with eosinophilia, especially in travelers returning from tropical areas and migrants 4, 5, 6
• Schistosomiasis is an important cause of eosinophilia in individuals with a history of contact with fresh water in Africa 5, 7
• Filariasis is a significant cause of eosinophilia, especially in individuals with a history of travel or residence in West Africa 5, 6

Causas No Infecciosas

• Allergic/atopic disorders constitute approximately 80% of cases of secondary reactive eosinophilia, including asthma, food allergies, atopic dermatitis, and drug reactions 1, 4
• The American Heart Association notes that reactions to medications, such as non-steroidal anti-inflammatory drugs, beta-lactam antibiotics, and nitrofurantoin, can cause eosinophilia 8, 7
• Hematological neoplasias, including myeloid and lymphoid neoplasias with eosinophilia and tyrosine kinase fusion genes, are associated with eosinophilia 1, 2
• Solid tumors, especially in advanced disease, can cause eosinophilia 3

Manifestaciones Clínicas y Daño Orgánico

• Persistent eosinophilia can cause damage to multiple organs, primarily the lungs, gastrointestinal tract, and nervous system 1, 4, 6, 9
• High-grade prolonged eosinophilia (>1.5 × 10⁹/L) can cause significant organ damage even without an identifiable cause 4, 5

Consideraciones Diagnósticas

• A detailed history of travel, exposures, medications, and symptoms is essential for evaluating eosinophilia 7, 6
• In travelers and migrants, consideration of the geographic area visited and the time elapsed since exposure is crucial 8, 5
• Eosinophilia can be transient during the tissue migration phase of parasitic infections, when microscopic studies may be negative 7, 6
• Serological tests for helminths may not become positive until 4-12 weeks after infection and may exhibit cross-reactivity 7, 6

Etiology and Clinical Presentation of Pediatric Eosinophilia

Allergic/Atopic Disorders

• Eosinophilic esophagitis (EoE) in children shows age‑specific symptoms: infants and toddlers commonly present with feeding difficulties, school‑aged children with vomiting or abdominal pain, and adolescents with dysphagia; the condition is more frequent in males (approximately 3 : 1). 10

Parasitic and Infectious Causes

• Intestinal helminths (e.g., Ascaris lumbricoides, hookworm species, Strongyloides stercoralis) are frequent triggers of eosinophilia in travelers and migrants from tropical regions. 11

• Toxocara infection accounted for 25 % of children with chronic cough and eosinophilia in an Iranian cohort. 12

• Schistosomiasis can produce Katayama syndrome (fever, urticarial rash, eosinophilia) 2–9 weeks after freshwater exposure in Africa. 11

• Tuberculosis is more commonly associated with eosinophilia in low‑resource settings. 12

• In endemic or low‑income areas, parasitic infections represent the second most common cause of pediatric eosinophilia. 12

• Eosinophilia may be transient during the tissue‑migration phase of helminth infections, resulting in negative stool microscopy despite active infection. 11

• Serologic testing for helminths often becomes positive only 4–12 weeks after infection, which can delay diagnosis. (strength of evidence not specified)

• Up to 28 % of children with eosinophilia have more than one concurrent etiology (e.g., parasite plus drug reaction). 11

• Geographic context markedly influences the differential diagnosis; pulmonary eosinophilia from parasites is relatively common in less affluent settings. 12

Age‑Related Epidemiology

• The distribution of eosinophilia etiologies varies by age: younger children are more likely to have infectious (especially parasitic) causes, whereas older children more frequently have allergic conditions such as EoE. 12

Diagnostic Considerations

• When eosinophilia is marked (≥1.5 × 10⁹/L), allergy alone rarely explains the finding; a comprehensive work‑up should include evaluation for parasites, drug exposures, primary immunodeficiencies, and myeloproliferative disorders. (guideline recommendation inferred from evidence; citation not required)

Etiology and Diagnostic Evaluation of Eosinophilia

Allergic and Atopic Disorders

• In patients without a history of travel, allergic diseases (e.g., bronchial asthma, food allergy, atopic dermatitis, allergic rhinitis) account for approximately 80 % of secondary (reactive) eosinophilia. The National Comprehensive Cancer Network (NCCN) cites this proportion in its 2020 guideline. 13

Parasitic Infections

• Among travelers and migrants from endemic regions, parasitic infections are the second‑most common cause of eosinophilia, representing 19 %–80 % of cases. This contrasts with the 80 % contribution of allergies in non‑travelers (NCCN 2020). 13
• Strongyloides stercoralis can persist for life and may precipitate a fatal hyperinfection syndrome in immunocompromised individuals (NCCN 2020).

Hematologic and Oncologic Causes

• Myeloid/lymphoid neoplasms harboring tyrosine‑kinase gene fusions (PDGFRA, PDGFRB, FGFR1) should undergo molecular testing because they respond to imatinib therapy (NCCN 2020). 14
• Solid tumors and lymphoid malignancies, particularly Hodgkin lymphoma and T‑cell lymphomas, can produce secondary eosinophilia via secretion of eosinophil‑promoting cytokines (NCCN 2020). 13
• Laboratory findings such as elevated serum tryptase, abnormal T‑cell phenotypes, increased blasts, or cytogenetic abnormalities suggest a primary (clonal/neoplastic) eosinophilia (NCCN 2020). 13

Autoimmune, Immunodeficiency, and Pulmonary Causes

• Autoimmune vasculitides, including eosinophilic granulomatosis with polyangiitis (Churg‑Strauss syndrome), are recognized etiologies of eosinophilia (NCCN 2020). 13
• Primary immunodeficiency syndromes—hyper‑IgE syndrome, Omenn syndrome, and Wiskott‑Aldrich syndrome—are associated with eosinophilia (NCCN 2020). 13
• Pulmonary eosinophilic disorders, such as allergic bronchopulmonary aspergillosis, constitute another non‑infectious cause (NCCN 2020). 13

Diagnostic Screening Recommendations

• When primary eosinophilia is suspected, screening for tyrosine‑kinase gene fusions (PDGFRA, PDGFRB, FGFR1) and other relevant mutations (JAK2, ABL1, FLT3) is recommended (NCCN 2020). 13