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EOSINOPHIL PRODUCTION

  • Eosinophil progenitors originate directly from the common myeloid progenitor after acquisition of interleukin (IL)-5 receptor alpha.

  • Differentiation is regulated by the transcription factors C/EBP-A and GATA-1 in addition to other factors such as GATA-2, PU.1, and FOG-1.

  • The normal adult marrow contains approximately 3% eosinophils.

  • Eosinophils differentiate in the marrow, migrate into the blood, and circulate for 25 hours before entering tissues.

EOSINOPHILIA

  • Eosinophils comprise 3% to 5% of leukocytes in the blood. The absolute eosinophil count in adults is 0.35 to 0.5 × 109 cells/L, with higher counts in neonates.

  • Eosinophilia is defined as an increased number of eosinophils in the blood. The degree of eosinophilia is described as:

    — Mild (<1.5 × 109/L)

    — Moderate or marked (1.5–5.0 × 109/L)

    — Severe or massive (>5.0 × 109/L)

  • Hypereosinophilia (HE) is defined as persistent eosinophilia greater than 1.5 × 109/L.

  • Eosinophilia is most commonly reactive (secondary) to other disorders.

  • The categorization of primary (clonal) eosinophilias was revised in the World Health Organization classification after the discovery of molecularly defined subtypes and includes myeloid/lymphoid neoplasms with eosinophilia and rearrangement of platelet-derived growth factor receptor alpha or beta (PDGFRA or PDGFRB), fibroblast growth factor receptor 1 (FGFR1), or Janus kinase 2 (JAK2), in addition to chronic eosinophilic leukemia, not otherwise specified (CEL, NOS)

  • A diagnosis of idiopathic HE requires the exclusion of all primary and secondary causes.

  • The term hypereosinophilic syndrome (HES) refers to a syndrome characterized by eosinophilia, organ infiltration by eosinophils, and a spectrum of clinical manifestations involving the lungs, heart, liver, and spleen.

  • Incidence rates of eosinophilia of 0.1% to 4% have been reported. The incidence of HES is much lower and estimated at 0.036 per 1000,000 person-years.

Clinical Manifestations

  • Eosinophilia is most commonly reactive (secondary) to other disorders such as infections, allergies, medications, autoimmune diseases, and malignancies (Table 32–1).

  • Clinical symptoms and disease manifestations of hypereosinophilic disorders are dependent on the involved organ (Table 32–2). Any organ system can be involved.

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TABLE 32–1 SECONDARY (REACTIVE) CAUSES OF EOSINOPHILIA
Category Examples
Infections

Parasitic (Strongyloides, Toxocara, Schistosoma, Echinococcus, Entamoeba, Cystoisospora, Ascaris, hookworm, Trichinella, Paragonimus, Clonorchis, filariasis [and related tropical pulmonary eosinophilia])

Viral (HIV)

Fungal (Coccidioides, Histoplasma, Cryptococcus, pneumocystis)

Mycobacterial (tuberculosis)

Bacterial

Allergies Asthma, allergic rhinitis, atopic dermatitis, allergic bronchopulmonary aspergillosis
Autoimmune Inflammatory bowel disease, celiac disease, eosinophilic granulomatosis with polyangiitis, rheumatoid arthritis, sarcoidosis, systemic sclerosis, Sjögren syndrome, bullous pemphigoid, IgG4-related disease, eosinophilic fasciitis
Medications Aspirin, NSAIDs, antimicrobials, DRESS syndrome
Malignancy Solid tumors (lung, renal, colon), Hodgkin and non-Hodgkin (T-cell) lymphoma
Metabolic Adrenal insufficiency
Immune deficiency Hyper IgE syndromes, Omenn syndrome, Wiskott-Aldrich syndrome
Other Gleich syndrome, acute or chronic ...

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