Eosinophilia

Eosinophilia is a topic covered in the Washington Manual of Medical Therapeutics.

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General Principles

  • Eosinophils are granulocytes that developed from bone marrow pluripotent progenitor cells.
  • Eosinophil maturation is promoted by interleukins (IL-5, IL-3), and granulocyte-macrophage colony-stimulating factor.
  • Eosinophils are normally seen in peripheral tissue such as mucosal tissues in the gastrointestinal and respiratory tracts. They are recruited to sites of inflammation.
  • Eosinophils can be involved in a variety of infectious, allergic, neoplastic, and idiopathic diseases.

Definition

  • A value >500 eosinophils/μL is defined as having eosinophilia.
  • The extent of eosinophilia can be categorized as mild (500–1500 cells/μL), moderate (1500–5000 cells/μL), or severe (>5000 cells/μL).
  • The degree of eosinophilia is not a reliable predictor of eosinophil-mediated organ damage.

Classification

  • Peripheral eosinophilia can be divided into primary, secondary, or idiopathic.
  • Primary eosinophilia is seen with hematologic disorders where there may be a clonal expansion of eosinophils (chronic eosinophilic leukemia) or a clonal expansion of cells that stimulate eosinophil production (chronic myeloid or lymphocytic disorders).
  • Secondary eosinophilia is also called reactive eosinophilia. It is a polyclonal expansion of eosinophils due to overproduction of IL-5. There are numerous causes such as parasites, allergic diseases, autoimmune disorders, toxins, medications, and endocrine disorders such as Addison disease.
  • Idiopathic eosinophilia is considered when primary and secondary causes are excluded.

Hypereosinophilic Syndrome

A proliferative disorder of eosinophils characterized by sustained eosinophilia >1500 cells/μL for ≥1 month documented on two occasions with eosinophil-mediated damage to organs such as the heart, gastrointestinal tract, kidneys, brain, and lung. All other causes of eosinophilia should be excluded to make the diagnosis.1

  • Hypereosinophilic syndrome (HES) occurs predominantly in men between the ages of 20 and 50 years and presents with insidious onset of fatigue, cough, and dyspnea.
  • Approximately 10%–15% HES patients have myeloproliferative disorders. Myeloproliferative variants of HES are characterized by constitutive expression of FIP1L1/PDGFRA fusion protein and elevated serum vitamin B12 levels.
  • Lymphocytic-variant HES (L-HES) accounts for 17%–26% HES patients. Unusual IL-5–producing T cells are found in L-HES.
  • Cardiac disease is a major cause of morbidity and mortality in patients with HES. At presentation, patients typically are in the late thrombotic and fibrotic stages of eosinophil-mediated cardiac damage with signs of a restrictive cardiomyopathy and mitral regurgitation. An echocardiogram may detect intracardiac thrombi, endomyocardial fibrosis, or thickening of the posterior mitral valve leaflet. Neurologic manifestations range from peripheral neuropathy to stroke or encephalopathy. Bone marrow examination reveals increased eosinophil precursors.
  • Acute eosinophilic leukemia is a rare myeloproliferative disorder that is distinguished from HES by several factors: an increased number of immature eosinophils in the blood and/or marrow, >10% blast forms in the marrow, and symptoms and signs compatible with an acute leukemia. Treatment is similar to other leukemias.
  • Lymphoma. Eosinophilia can present in any T- or B-cell lymphoma. As many as 5% of patients with non-Hodgkin lymphoma and up to 15% of patients with Hodgkin lymphoma have modest peripheral blood eosinophilia. Eosinophilia in Hodgkin lymphoma has been correlated with IL-5 messenger RNA expression by Reed–Sternberg cells.
  • Atheroembolic disease. Cholesterol embolization can lead to eosinophilia, eosinophiluria, renal dysfunction, livedo reticularis, purple toes, and increased erythrocyte sedimentation rate (ESR).
  • Immunodeficiency. Hyper-IgE syndrome, autoimmune lymphoproliferative syndrome, and Omenn syndrome can present with recurrent infections, dermatitis, and eosinophilia.

Epidemiology

In industrialized nations, peripheral blood eosinophilia is most often due to atopic disease, whereas helminthic infections are the most common cause of eosinophilia in the rest of the world.

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General Principles

  • Eosinophils are granulocytes that developed from bone marrow pluripotent progenitor cells.
  • Eosinophil maturation is promoted by interleukins (IL-5, IL-3), and granulocyte-macrophage colony-stimulating factor.
  • Eosinophils are normally seen in peripheral tissue such as mucosal tissues in the gastrointestinal and respiratory tracts. They are recruited to sites of inflammation.
  • Eosinophils can be involved in a variety of infectious, allergic, neoplastic, and idiopathic diseases.

Definition

  • A value >500 eosinophils/μL is defined as having eosinophilia.
  • The extent of eosinophilia can be categorized as mild (500–1500 cells/μL), moderate (1500–5000 cells/μL), or severe (>5000 cells/μL).
  • The degree of eosinophilia is not a reliable predictor of eosinophil-mediated organ damage.

Classification

  • Peripheral eosinophilia can be divided into primary, secondary, or idiopathic.
  • Primary eosinophilia is seen with hematologic disorders where there may be a clonal expansion of eosinophils (chronic eosinophilic leukemia) or a clonal expansion of cells that stimulate eosinophil production (chronic myeloid or lymphocytic disorders).
  • Secondary eosinophilia is also called reactive eosinophilia. It is a polyclonal expansion of eosinophils due to overproduction of IL-5. There are numerous causes such as parasites, allergic diseases, autoimmune disorders, toxins, medications, and endocrine disorders such as Addison disease.
  • Idiopathic eosinophilia is considered when primary and secondary causes are excluded.

Hypereosinophilic Syndrome

A proliferative disorder of eosinophils characterized by sustained eosinophilia >1500 cells/μL for ≥1 month documented on two occasions with eosinophil-mediated damage to organs such as the heart, gastrointestinal tract, kidneys, brain, and lung. All other causes of eosinophilia should be excluded to make the diagnosis.1

  • Hypereosinophilic syndrome (HES) occurs predominantly in men between the ages of 20 and 50 years and presents with insidious onset of fatigue, cough, and dyspnea.
  • Approximately 10%–15% HES patients have myeloproliferative disorders. Myeloproliferative variants of HES are characterized by constitutive expression of FIP1L1/PDGFRA fusion protein and elevated serum vitamin B12 levels.
  • Lymphocytic-variant HES (L-HES) accounts for 17%–26% HES patients. Unusual IL-5–producing T cells are found in L-HES.
  • Cardiac disease is a major cause of morbidity and mortality in patients with HES. At presentation, patients typically are in the late thrombotic and fibrotic stages of eosinophil-mediated cardiac damage with signs of a restrictive cardiomyopathy and mitral regurgitation. An echocardiogram may detect intracardiac thrombi, endomyocardial fibrosis, or thickening of the posterior mitral valve leaflet. Neurologic manifestations range from peripheral neuropathy to stroke or encephalopathy. Bone marrow examination reveals increased eosinophil precursors.
  • Acute eosinophilic leukemia is a rare myeloproliferative disorder that is distinguished from HES by several factors: an increased number of immature eosinophils in the blood and/or marrow, >10% blast forms in the marrow, and symptoms and signs compatible with an acute leukemia. Treatment is similar to other leukemias.
  • Lymphoma. Eosinophilia can present in any T- or B-cell lymphoma. As many as 5% of patients with non-Hodgkin lymphoma and up to 15% of patients with Hodgkin lymphoma have modest peripheral blood eosinophilia. Eosinophilia in Hodgkin lymphoma has been correlated with IL-5 messenger RNA expression by Reed–Sternberg cells.
  • Atheroembolic disease. Cholesterol embolization can lead to eosinophilia, eosinophiluria, renal dysfunction, livedo reticularis, purple toes, and increased erythrocyte sedimentation rate (ESR).
  • Immunodeficiency. Hyper-IgE syndrome, autoimmune lymphoproliferative syndrome, and Omenn syndrome can present with recurrent infections, dermatitis, and eosinophilia.

Epidemiology

In industrialized nations, peripheral blood eosinophilia is most often due to atopic disease, whereas helminthic infections are the most common cause of eosinophilia in the rest of the world.

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