Eosinophilia

Eosinophilia is a condition in which the

Informally, blood eosinophil levels are often regarded as mildly elevated at counts of 500–1,500/μL, moderately elevated between 1,500 and 5,000/μL, and severely elevated when greater than 5,000/μL. Elevations in blood eosinophil counts can be transient, sustained, recurrent, or cyclical.[4]^[5]

Eosinophil counts in human blood normally range between 100 and 500 per/μL. Maintenance of these levels results from a balance between production of eosinophils by

Based on their causes, hypereosinophilias can be sorted into subtypes. However, cases of eosinophilia, which exhibit eosinophil counts between 500 and 1,500/μL, may fit the clinical criteria for, and thus be regarded as falling into, one of these hypereosinophilia categories: the cutoff of 1,500/μL between hypereosinophilia and eosinophilia is somewhat arbitrary. There are at least two different guidelines for classifying hypereosinophilia/eosinophilia into subtypes. The General Haematoloy and Haemato-oncology Task Forces for the British Committee for Standards in Haematology classifies these disorders into a) Primary, i.e. caused by abnormalities in the eosinophil cell line; b) Secondary, i.e. caused by non-eosinophil disorders; and c) Idiopathic, cause unknown.[4] The World Health Organization classifies these disorders into a) Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1 (i.e. high eosinophil blood counts caused by mutations in the eosinophil cell line of one of these three genes), 'b) Chronic eosinophilic leukemia, and c) the Idiopathic hypereosinophiic syndrome. In the latter classification, secondary hypereosinophilia/eosinophilia is not viewed as a true disorder of eosinophils.^[5][10] Here these two classifications are merged and expanded to include the many forms of secondary, i.e. reactive hypereosinophilia/eosinophilia, disorders and also includes another subtype, organ-restricted hypereosinophilias, a disorder in which eosinophil-mediated tissue damage is restricted to one organ and is often but not always associated with increased blood eosinophil counts.^{[citation needed]}

Primary hypereosinophilia

Primary hypereosinophilia is due to the development of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a significantly mutated ancestor cell. The clone may prove to be benign,

Clonal hypereosinophilia is hypereosinophilia caused by a pre-malignant or malignant clone of eosinophils that bear mutations in genes for

Chronic eosinophilic leukemia, not otherwise specified (i.e. CEL, NOS), is a

Familial eosinophilia is a rare

Idiopathic hypereosinophilia (also termed hypereosinophilia of undetermined significance, i.e. HE_US) is a disorder characterized by an increase in eosinophil blood counts above 1,500/μL, as detected on at least 2 separate examinations. The disorder cannot be associated with eosinophil-based tissue damage or a primary or secondary cause of eosinophilia. That is, it is a diagnosis of exclusion and has no known cause. Over time, this disorder can resolve into a primary hypereosinophilia, typically clonal hypereosinophilia, chronic eosinphilic leukemia, or an eosinophilia associated with another hematological leukemia. The disorder may also become associated with tissue or organ damage and therefore be diagnosed as the hypereosinophilic syndrome. Idiopathic hypereosinophilia is treated by observation to detect development of the cited more serious disorders.[5]^[18]

Idiopathic hypereosiophilic syndrome

The idiopathic hypereosinophilic syndrome is a disorder characterized by hypereosiophilia that is associated with eosinophil-based tissue or organ damage. While almost any organ or tissue may be damaged, the lung, skin, heart, blood vessels, sinuses, kidneys, and brain are the most commonly affected.^[7] The World Health Organization restrict this diagnosis to cases which have no well-defined cause. That is, all cases of secondary (i.e. reactive) eosinophilia (including lymphocyte-variant hypereosinophilia) and primary hypereosinophilia (including chronic eosinophilic leukemia (NOS), clonal eosinophilia, and hypereosinophilia associated with hematological malignancies) are excluded from this diagnosis.^[5][7]

Secondary hypereosinophilia

Secondary (or reactive) eosinophilias are non-clonal increases in blood eosinophil levels caused by an underlying disease. The

Certain types of food allergy disorders may also be associated with eosinophilia or, less commonly, hypereosinophilia. Allergic eosinophilic esophagitis and the food protein-induced enterocolitis syndrome are commonly associated with increased blood eosinophil levels.^[22][23]

Drugs

A wide range of drugs are known to cause hypereosinophilia or eosinophilia accompanied by an array of

Hodgkin lymphoma (Hodgkin's disease) often elicits severe eosinophilia; however, non-Hodgkin lymphoma and leukemia produce less marked eosinophilia.^[3] Of solid tumor neoplasms, ovarian cancer is most likely to provoke eosinophilia, though any other cancer can cause the condition.^[3] Solid epithelial cell tumors have been shown to cause both tissue and blood eosinophilia, with some reports indicating that this may be mediated by interleukin production by tumor cells, especially IL-5 or IL-3.^[2] This has also been shown to occur in Hodgkin lymphoma, in the form of IL-5 secreted by Reed-Sternberg cells.^[2] In primary cutaneous T cell lymphoma, blood and dermal eosinophilia are often seen. Lymphoma cells have also been shown to produce IL-5 in these disorders. Other types of lymphoid malignancies have been associated with eosinophilia, as in lymphoblastic leukemia with a translocation between chromosomes 5 and 14 or alterations in the genes which encode platelet-derived growth factor receptors alpha or beta.^[2][25] Patients displaying eosinophilia overexpress a gene encoding an eosinophil hematopoietin. A translocation between chromosomes 5 and 14 in patients with acute B lymphocytic leukemia resulted in the juxtaposition of the IL-3 gene and the immunoglobulin heavy-chain gene, causing overproduction production of IL-3, leading to blood and tissue eosinophilia.^[2][26]

Primary immunodeficiency diseases

Primary

Lymphocyte-variant hypereosinophilia is a disorder attributed to the expansion of a cytokine-producing, aberrant population of a particular T-cell phenotype. The disorder is clonal with regard to the production of abnormal T-cell lymphocytes not eosinophils which appear phenotypically normal. The phenotypically aberrant lymphocytes function abnormally by stimulating the proliferation and maturation of

IgG4-related disease or Immunoglobulin G4-related disease is a condition

Angiolymphoid hyperplasia with eosinophilia is a disorder initially classified as a form of IgG4-related diseases but now considered a distinct entity. The disorder involves inflamed benign tumors of the vasculature in skin and, less commonly, other tissues. The tumors consist of histiocytoid endothelial cells prominently infiltrated by lymphocytes and eosinophils and is associated with hypereosinophilia or eosinophilia.^[30]

Cholesterol embolism

Transient, fluctuating hypereosinophilia occurs in 60–80% of individuals with

Harm resulting from untreated eosinophilia potentially varies with cause. During an allergic reaction, the release of histamine from mast cells causes vasodilation which allows eosinophils to migrate from the blood and localize in affected tissues. Accumulation of eosinophils in tissues can be significantly damaging. Eosinophils, like other granulocytes, contain granules (or sacs) filled with digestive enzymes and cytotoxic proteins which under normal conditions are used to destroy parasites but in eosinophilia these agents can damage healthy tissues. In addition to these agents, the granules in eosinophils also contain inflammatory molecules and cytokines which can recruit more eosinophils and other inflammatory cells to the area and hence amplify and perpetuate the damage. This process is generally accepted to be the major inflammatory process in the pathophysiology of atopic or allergic asthma.^[33]

Diagnosis

Diagnosis is by

• Allergic disorders
  • Asthma^[34]
  • Hay fever^[34]
  • Drug allergies^[34]
  • Allergic skin diseases^[34]
    • Pemphigus^[34]
    • Dermatitis herpetiformis
• IgG4-related disease
• Parasitic infections^[34]
• Addison's disease and stress-induced suppression of adrenal gland function^[35]
• Some forms of malignancy
  • Acute lymphoblastic leukemia
  • Chronic myelogenous leukemia
  • Eosinophilic leukemia
  • Clonal eosinophilia^[17]
  • Hodgkin lymphoma^[34]
  • Some forms of non-Hodgkin lymphoma^[34]
  • Lymphocyte-variant hypereosinophilia
  • Systemic mastocytosis
• Systemic autoimmune diseases^[34]
  • Systemic lupus erythematosus
  • Kimura disease^[36]
  • Eosinophilic granulomatosis with polyangiitis^[37]
  • Eosinophilic fasciitis^[38]
  • Eosinophilic myositis^[39]
• Eosinophilic myocarditis^[40]
• Eosinophilic esophagitis^[41]
• Eosinophilic gastroenteritis^[42]
• Cholesterol embolism (transiently)^[34]
• Coccidioidomycosis (Valley fever), a fungal disease prominent in the US Southwest.^[43]
• Human immunodeficiency virus
  infection
• Interstitial nephropathy
• Idiopathic hypereosinophilic syndrome.^[25]
• Congenital disorders
  • Hyperimmunoglobulin E syndrome, an immune disorder characterized by high levels of serum IgE^[39]
  • Omenn syndrome^[39]
  • Familial eosinophilia^[16]

See also

• Acidophile (histology)

References