accompanied by less severe (e.g. non-dress syndrome) symptoms include tetracyclins, doxycycline, linezolid, nitrofurantoin, metronidazole, carbamazepine, phenobarbital, lamotrigine, valproate, desipramine, amitriptyline, fluoxetine, piroxicam, diclofenac, ace inhibitors, abacavir, nevirapine, ranitidine, cyclosporin, and hydrochlorothiazide. the toxic oil syndrome is associated with hypereosinophilia/eosinophilia and systemic symptoms due to one or more contaminants in rapeseed oil and the eosinophilia–myalgia syndrome, also associated with hypereosinophilia, appears due to trace contaminants in certain commercial batches of the amino acid, l-tryptophan. 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 has, 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. malignancies certain malignancies cause a secondary eosinophilia or, less commonly, hypereosinophilia. these increases in blood eosinophils appear due to the release of stimulatory cytokines or invasion of the bone marrow and thereby irritation of resident eosinophils or their precursors. malignancies associated with these effects include gastric, colorectal, lung, bladder, and thyroid cancers, as well as squamous cell cancers of the cervix, vagina, penis, skin, and nasopharyrnx. some hematological malignancies are likewise associated with secondary rises in blood eosinophil counts; these include hodgkin disease, certain t-cell lymphomas, acute myeloid leukemia, the myelodysplastic syndromes, many cases of systemic mastocytosis, chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelofibrosis, chronic myelomonocytic leukemia, and certain cases of t-lymphoblastic leukemia/lymphoma-associated or myelodysplastic–myeloproliferative syndrome-associated eosinophilias. 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. primary immunodeficiency diseases main article: primary immunodeficiency primary immunodeficiency diseases are inborn errors in the immune system due to defective genes. certain of these disorders are sometimes or often associated with hypereosinophilia. the list of such disorders includes zap70 deficiency (defective zap70 gene), cd3gamma chain deficiency (defective cd3g gene), mchii deficiency (defective rfxank gene), wiskott–aldrich syndrome (defective was gene), ipex syndrome (defective ipex gene), cd40 gene defect, and autoimmune lymphoproliferative syndrome (defective fas receptor gene). more than 30 other primary immunodeficiency diseases are sometimes associated with modest increases in eosinophil counts, i.e. eosinophilia. the hyperimmunoglobulin e syndrome is associated with hypereosinophilia or eosinophilia due to mutations in any one of the following genes: stat3, dock8, pgm3, spink5, and tyk2 (see mutations in the hymperimmoglobulin e syndrome). omenn syndrome is a severe combined immunodeficiency disease characterized by skin rash, slenomegaly, and lymphadenopathy due to a causative mutation in rag1, rag2, or, more rarely, one of several other genes. lymphocyte-variant hypereosinophilia main article: lymphocyte-variant hypereosinophilia 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 bone marrow eosinophil-precursor cells which in studied cases appears due to their excess production of interleukin 5, interleukin 3, or interleukin 13. the disorder is usually indolent but infrequently progresses to t-cell lymphoma or sezary syndrome. accumulation of partial deletions in the short arm of chromosome 6, the long arm of chromosome 10, or the acquirement of an extra chromosome (i.e. trisomy) 7) in t-cells or the proliferation of lymphocytes with the cd3 negative, cd41 positive immunophenotype may occur during the disorders progression to lymphoma. reports on treatment of the disorder are rare. in on study of 16 lymphocyte-variant hypereosinophilia patients with the aberrant cd3 negative, cd41 positive immunophenotype, good responds to corticosteroid drugs were uniform but 16 ultimately required corticosteroid-sparing agents. hydroxyurea and imatinib are less likely to have efficacy in this variant of hypereosinophilia than in many cases of clonal eosinophilia or chronic eosinophilic leukemia. gleich's syndrome main article: gleich's syndrome gleich's syndrome, which may be a form of lymphocyte-variant hypereosinophilia, involves hypereosinophilia, elevated blood levels of igm antibodies, and clonal expansion of t cells. similar to lymphocyte=variant hypereosinophilia, the increased levels of blood eosinophils in gleich's syndrome is thought to be secondary to the secretion of eosinophil-stimulating cytokines by a t cell clones. igg4-related disease main article: igg4-related disease igg4-related disease or immunoglobulin g4-related disease is a condition dacryoadenitis, sialadenitis, lymphadentitis, and pancreatitis (i.e. inflammation of the lacrimal glands, salivary glands, lymph nodes, and pancreas, respectively) plus retroperitoneal fibrosis. less commonly, almost any other organ or tissue except joints and brain may be beleaguered by the inflammatory disorder. about 1/3 of cases exhibit eosinophilia or, rarely, hypereosinophilia. this increase in blood eosinophil count is often associated with abnormal t-lymphocyte clones (e.g. increased numbers of cd4 negative, cd7 positive t cells, cd3 negative, cd4 positive t cells, or cd3 positive, cd4 negative, cd8 negative t cells) and is thought to be secondary to these immunological disturbances. the disorder often exhibits are recurrent-relapsing course and is highly responsive to corticosteroids or rituximab as first-line therapy and interferon gamma as second-line therapy. angiolymphoid hyperplasia with eosinophilia main article: angiolymphoid hyperplasia with eosinophilia 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. cholesterol embolism main article: cholesterol embolism transient, fluctuating hypereosinophilia occurs in 60%-80% of individuals with cholesterol embolisms. in this disorder, cholesterol crystals located in an atherosclerotic plaque of a large artery dislodge, travel downstream in the blood, and clog smaller arteries. this results in obstructive damage to multiple organs and tissues. affected tissues exhibit acute inflammation involving eosinophils, neutrophils, monocytes, lymphocytes, and plasma cells. the cause for this hypereosinophilic response is not known. adrenal insufficiency a class of steroid hormones secreted by the adrenal gland, glucocorticoids, inhibit eosinophil proliferation and survival. in adrenal insufficiency, low levels of these hormones allow increased eosinophil proliferation and survival. this leads to increases in blood eosinophil levels, typically eosinophilia and, less commonly, hypereosinophilia. organ-restricted hypereosinophilias hypereosinophilia may occur in the setting of damage to a single specific organ due to a massive infiltration by eosinophils. this disorder is sub-classified based on the organ involved and is not considered to be a form of primary hypereosinophilia, secondary hypereosinophilia, or the idiopathic hypereosinophilic syndrome because: a) the eosinophils associated with the disorder have not been shown to be clonal in nature; b) a reason for the increase in blood eosinophils has not been determined; c) organ damage has not been shown to be due to eosinophils; and d) the disorder in each individual case typically is limited to the affected organ. examples of organ-restricted hypereosinophilia include eosinophilic myocarditis, eosinophilic esophagitis, eosinophilic gastroenteritis, eosinophilic cystitis, eosinophilic pneumonia, eosinophilic fasciitis, eosinophilic folliculitis, eosinophilic cellulitis, eosinophilic vasculitis, and eosinophilic ulcer of the oral mucosa. other examples of organ-restricted hepereosinophilia include those involving the heart, kidney, liver, colon, pulmonary pleurae, peritoneum, fat tissue, myometrium, and synovia. pathophysiology ige-mediated eosinophil production is induced by compounds released by basophils and mast cells, including eosinophil chemotactic factor of anaphylaxis, leukotriene b4 and serotonin mediated release of eosinophil granules occur, 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 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 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. list of causes 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 asthma hay fever drug allergies allergic skin diseases pemphigus dermatitis herpetiformis igg4-related disease parasitic infections addison's disease and stress-induced suppression of adrenal gland function some forms of malignancy acute lymphoblastic leukemia chronic myelogenous leukemia eosinophilic leukemia clonal eosinophilia hodgkin lymphoma some forms of non-hodgkin lymphoma lymphocyte-variant hypereosinophilia systemic mastocytosis systemic autoimmune diseases systemic lupus erythematosus kimura disease eosinophilic granulomatosis with polyangiitis eosinophilic fasciitis eosinophilic myositis eosinophilic myocarditis eosinophilic esophagitis eosinophilic gastroenteritis 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. congenital disorders hyperimmunoglobulin e syndrome omenn syndrome familial eosinophilia