Eosinophils in the peripheral blood of a patient with idiopathic eosinophilia
|Classification and external resources|
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 4.5×108/L (450/µL). Eosinophils usually account for less than 7% of the circulating leukocytes. A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being some form of allergic reaction or parasitic infection. Diagnosis of eosinophilia is via a complete blood count (CBC), but diagnostic procedures directed at the underlying cause vary depending on the suspected condition(s). An absolute eosinophil count is not generally needed if the CBC shows marked eosinophilia. The location of the causal factor can be used to classify eosinophilia into two general types: extrinsic, in which the factor lies outside of the eosinophil cell lineage; and intrinsic eosinophilia, which denotes etiologies within the eosiniphil cell line. Specific treatments are dictated by the causative condition, though in idiopathic eosinophilia, the disease may be controlled with corticosteroids. Eosinophilia is not a disorder (rather, only a sign) unless it is idiopathic.
Eosinophilia can be idiopathic (primary) or, more commonly, secondary to another disease. In the Western World, allergic or atopic diseases are the most common causes, especially those of the respiratory or integumentary systems. In the developing world, parasites are the most common cause. A parasitic infection of nearly any bodily tissue can cause eosinophilia. Diseases that feature eosinophilia as a sign include:
- Allergic disorders
- Eosinophilic esophagitis
- Eosinophilic gastroenteritis
- Parasitic infections
- Addison's disease
- Some forms of malignancy
- Systemic autoimmune diseases (e.g. SLE, idiopathic eosinophilic synovitis)
- Systemic mastocytosis
- Some forms of vasculitis (e.g. eosinophilic granulomatosis with polyangiitis)
- Cholesterol embolism (transiently)
- Coccidioidomycosis (Valley fever), a fungal disease prominent in the US Southwest.
- Human immunodeficiency virus infection
- Interstitial nephropathy
- Hyperimmunoglobulin E syndrome, an immune disorder characterized by high levels of serum IgE
- Idiopathic hypereosinophilic syndrome.
Hodgkin lymphoma (Hodgkin's disease) often elicits severe eosinophilia; however, non-Hodgkin lymphoma and leukemia produce less marked eosinophilia. Of solid tumor neoplasms, ovarian cancer is most likely to provoke eosinophilia, though any other cancer can cause the condition. 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. This has also been shown to occur in Hodgkin lymphoma, in the form of IL-5 secreted by Reed-Sternberg cells. 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. 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.
Allergic reactions to drugs are a common cause of eosinophilia, with manifestations ranging from diffuse maculopapular rash, to severe life-threatening drug reactions with eosinophilia and systemic symptoms (DRESS). Drugs that have been shown to cause DRESS are aromatic anticonvulsants and other antiepileptics, sulfonamides, allopurinol, nonsteroidal anti-inflammatory drugs (NSAIDs), some antipsychotics such as risperidone, and certain antibiotics. Phenibut, an analogue of the neurotransmitter GABA, has also been implicated in high doses. The reaction which has been shown to be T-cell mediated may also cause eosinophilia-myalgia syndrome.
IgE mediated eosinophil production is induced by compounds released by basophils and mast cells, including eosinophil chemotactic factor of anaphylaxis, leukotriene B4, complement complex (C5-C6-C7), interleukin 5, and histamine (though this has a narrow range of concentration).
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.
Diagnosis is by complete blood count (CBC). However, in some cases, a more accurate absolute eosinophil count may be needed. Medical history is taken, with emphasis on travel, allergies and drug use. Specific test for causative conditions are performed, often including chest x-ray, urinalysis, liver and kidney function tests, and serologic tests for parasitic and connective tissue diseases. The stool is often examined for traces of parasites (i.e. eggs, larvae, etc.) though a negative test does not rule out parasitic infection; for example, trichinosis requires a muscle biopsy. Elevated serum B12 or low white blood cell alkaline phosphatase, or leukocytic abnormalities in a peripheral smear indicates a disorder of myeloproliferation. In cases of idiopathic eosinophilia, the patient is followed for complications. A brief trial of corticosteroids can be diagnostic for allergic causes, as the eosinophilia should resolve with suppression of the immune over-response. Neoplastic disorders are diagnosed through the usual methods, such as bone marrow aspiration and biopsy for the leukemias, MRI/CT to look for solid tumors, and tests for serum LDH and other tumor markers.
Treatment is directed toward the underlying cause. However, in primary eosinophilia, or if the eosinophil count must be lowered, corticosteroids such as prednisone may be used. However, immune suppression, the mechanism of action of corticosteroids, can be fatal in patients with parasitosis.
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