What are the causes of eosinophilia (elevated eosinophil count)?

From the Guidelines

Eosinophilia is most commonly caused by allergic disorders, such as asthma, hay fever, and atopic dermatitis, as well as parasitic infections, particularly those involving tissue-invasive helminths like Strongyloides, Ascaris, and hookworms, especially in travelers or immigrants from endemic areas. The causes of eosinophilia can be broadly categorized into several groups, including:

• Allergic disorders, which are the most common cause, accounting for approximately 80% of cases 1
• Parasitic infections, which are a significant cause, especially in travelers or immigrants from endemic areas 1
• Drug reactions, which can trigger eosinophilia, with common culprits including antibiotics, NSAIDs, anticonvulsants, and allopurinol
• Autoimmune and inflammatory conditions, such as eosinophilic granulomatosis with polyangiitis, inflammatory bowel disease, and certain connective tissue disorders
• Hematologic malignancies, including certain leukemias, lymphomas, and mastocytosis, which may present with elevated eosinophil counts
• Hypereosinophilic syndrome, which is a diagnosis of exclusion when eosinophil counts exceed 1,500/μL for at least six months without an identifiable cause

According to the most recent and highest quality study, helminth infections are the commonest identifiable cause of eosinophilia in returning travelers and migrants, with diagnosis rates varying from 19% to 80% 1. It is essential to recognize and treat these infections, as they can cause long-term health problems, such as hyperinfection syndrome in those who become immunocompromised. The evaluation of eosinophilia should include a thorough history focusing on travel, medications, and symptoms of allergic or systemic disease, along with appropriate laboratory testing based on clinical suspicion.

In cases where eosinophilia is persistent, patients should be referred to a hematologist for further investigations once infectious causes have been excluded or treated 1. Additionally, any patient presenting with evidence of end-organ damage needs urgent medical assessment and consideration of emergency treatment 1.

Overall, the management of eosinophilia requires a comprehensive approach, taking into account the various potential causes and the need for prompt treatment to prevent long-term health problems.

From the FDA Drug Label

The demographics and baseline characteristics of patients in this trial are provided in Table 12. Table 12 Demographics and Baseline Characteristics in HES HES = Hypereosinophilic Syndrome, SD = standard deviation. N = 108 Mean age, years (SD) 46.0 (15.78) Female, n (%) 57 (53) White, n (%) 100 (93) Mean duration of HES, years 5. 55 Historical HES flares for the trial entry criteria were defined as HES-related worsening of clinical symptoms or blood eosinophil counts requiring an escalation in therapy

The causes of eosinophilia are not directly stated in the provided drug label. However, it can be inferred that hypereosinophilic syndrome (HES) is a condition characterized by elevated eosinophil counts, and the label mentions that patients with non-hematologic secondary HES (e.g., drug hypersensitivity, parasitic helminth infection, HIV infection, non-hematologic malignancy) or FIP1L1-PDGFRα kinase-positive HES were excluded from the trial.

• Hypereosinophilic syndrome (HES) is associated with eosinophilia.
• Some possible causes of secondary HES include:
  • Drug hypersensitivity
  • Parasitic helminth infection
  • HIV infection
  • Non-hematologic malignancy 2

From the Research

Causes of Eosinophilia

• Eosinophilia can be caused by various factors, including:
  • Parasitic diseases 3, 4
  • Allergic diseases 3, 5
  • Autoimmune diseases 3
  • Connective tissue diseases 3
  • Rheumatologic diseases 3, 5
  • Primary eosinophilia, such as hypereosinophilic syndrome 3, 6, 7
  • Malignant states 3
• Eosinophilia can also be associated with infectious, neoplastic, and rare idiopathic disorders 5
• The etiology of eosinophilia remains unproven in the majority of cases, despite advances in molecular and immunologic techniques 5

Classification of Eosinophilia

• The World Health Organization endorses a semi-molecular classification scheme of disease subtypes, including:
  • Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 6, 7
  • Chronic eosinophilic leukemia, not otherwise specified (CEL, NOS) 6, 7
  • Lymphocyte-variant hypereosinophilia, an aberrant T-cell clone-driven reactive eosinophilia 6, 7
  • Idiopathic hypereosinophilic syndrome (HES), a diagnosis of exclusion 6, 7

Diagnosis and Treatment

• Diagnostic evaluation of primary eosinophilias relies on a combination of tests, including morphologic review of the blood and marrow, standard cytogenetics, and flow immunophenotyping 6, 7
• Treatment goals include mitigating eosinophil-mediated organ damage, and may involve:
  • Watch and wait approach with close follow-up for milder forms of eosinophilia 6, 7
  • Imatinib for patients with rearranged PDGFRA or PDGFRB 6, 7
  • Corticosteroids as first-line therapy for patients with lymphocyte-variant hypereosinophilia and HES 6, 7
  • Hydroxyurea and interferon-α as initial treatment and in steroid-refractory cases of HES 6, 7
  • Albendazole as a potential treatment for eosinophilia of unknown etiology 4