Chapter 32: Eosinophils and Their Disorders

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.