Hypereosinophilic Syndrome

(Idiopathic hypereosinophilic syndrome)

Hypereosinophilic syndrome (HES) is characterized as peripheral blood eosinophilia with involvement of organ systems or disorders related to the absence of parasitic, allergic or other causes of eosinophilia directly with the eosinophilia associated. The symptoms are varied and depend on the impairment of the respective organs. The diagnosis involves the exclusion of other causes of eosinophilia plus bone marrow and cytogenetic tests. Usually the treatment begins with prednisone, and, in a frequently occurring subtype, with imatinib.

The hypereosinophilic syndrome is characterized by peripheral blood eosinophilia> 1500 / ul that lasts ? 6 months. Originally, the hypereosinophilic syndrome has been described as idiopathic disorder, but today it is known that it is the result of various diseases such. may be T. known cause. As limiting the original definition, is considered that they are not patients with the same anomalies (for. Example, chromosomal defects), which are known as causes of hypereosinophilic syndrome, but do not fulfill the classical HES diagnostic criteria regarding the degree or duration of eosinophilia , Another limitation is that some patients with eosinophilia and organ damage that are characteristic of a hypereosinophilic syndrome within the first six months needed to confirm the diagnosis according to the established criteria need treatment.

Hypereosinophilic syndrome (HES) is characterized as peripheral blood eosinophilia with involvement of organ systems or disorders related to the absence of parasitic, allergic or other causes of eosinophilia directly with the eosinophilia associated. The symptoms are varied and depend on the impairment of the respective organs. The diagnosis involves the exclusion of other causes of eosinophilia plus bone marrow and cytogenetic tests. Usually the treatment begins with prednisone, and, in a frequently occurring subtype, with imatinib. The hypereosinophilic syndrome is characterized by peripheral blood eosinophilia> 1500 / ul that lasts ? 6 months. Originally, the hypereosinophilic syndrome has been described as idiopathic disorder, but today it is known that it is the result of various diseases such. may be T. known cause. As limiting the original definition, is considered that they are not patients with the same anomalies (for. Example, chromosomal defects), which are known as causes of hypereosinophilic syndrome, but do not fulfill the classical HES diagnostic criteria regarding the degree or duration of eosinophilia , Another limitation is that some patients with eosinophilia and organ damage that are characteristic of a hypereosinophilic syndrome within the first six months needed to confirm the diagnosis according to the established criteria need treatment. The hypereosinophilic syndrome is rare, has an unknown prevalence and usually affects patients aged 20 to 50 years. Only a few patients with prolonged eosinophilia develop organ damage that characterize a hypereosinophilic syndrome. Although any organ can be involved, heart, lungs, spleen, skin and nervous system are typically affected. A cardiac involvement can cause significant morbidity and mortality. Subtypes There are major subtypes (subtypes of hypereosinophilien syndrome): Myeloproliferative variant lymphoproliferative variant The myeloproliferative variant is often accompanied by a small interstitial deletion in chromosome 4 at the location CHIC2 that (the FIP1L1 / PDGFRA-associated fusion that for the tyrosine kinase activity and thus the transformation of hematopoietic cells is) gives. Patients often have splenomegaly thrombocytopenia anemia Increased vitamin B12 serum levels Hypogranuläre or vacuolated eosinophils myelofibrosis patients with this subtype often get a endomyocardial fibrosis or may rarely develop acute myeloid or lymphoblastic leukemia. Patients with FIP1L1 / PDGFRA fusion gene are often associated male sex and talking on treatment with low-dose imatinib at. The lymphoproliferative variant shows by a clonal T-cell population with aberrant phenotype. KCV is a clonal T cell receptor-conversion. Patients have frequently angioedema, skin lesions or both hypergammaglobulinemia (especially IgE) Circulating immune complexes (sometimes with serum sickness) They also react more to corticosteroids and occasionally develop a T-cell lymphoma. Other HES variants include chronic eosinophilic leukemia, DC syndrome (cyclic eosinophilia and angioedema), familial hypereosinophilic syndrome (isolated on 5q 31-33) as well as other organ-specific syndromes. Hyperleukocytosis can (> 100,000 / ul z. B.) occur in patients with eosinophilic leukemia and high Eosinophilenwerten. Eosinophils may form aggregates that clog small blood vessels, resulting in tissue ischemia and micro infarcts. Often hypoxia of the brain or the lungs occurs (encephalopathy z. B., dyspnea or respiratory insufficiency) on. Subtypes of hypereosinophilien syndrome feature myeloproliferative variant lymphoproliferative Variant Genetics small interstitial deletion in chromosome 4 FIP1L1 / PDGFRA-associated fusion clonal T-cell population with a different phenotype Clinical manifestations and laboratory findings anemia Increased vitamin B12 serum levels endomyocardial fibrosis Hypogranuläre or vacuolated eosinophils myelofibrosis splenomegaly thrombocytopenia angioedema Circulating immune complexes (sometimes with serum sickness) Hypergammaglobulinemia (particularly IgE) lesions Increased risk of other diseases Acute Lymphocytic Leukemia Acute myeloid leukemia T-cell lymphoma response to drug imatinib and other tyrosine kinase inhibitors corticosteroids symptoms and complaints The symptoms are varied and depend on which impaired organs (b changes ei patients with hypereosinophilic syndrome). Changes in patients with hypereosinophilic syndrome system frequency manifestations Constitutional symptoms ? 50% anorexia fatigue fever myalgias weakness weight loss Cardiopulmonary> 70% Mural thrombi embolism restrictive or infiltrative cardiomyopathy or mitral or tricuspid regurgitation with coughing, shortness of breath, heart failure, arrhythmias, endomyocardial disease, pulmonary infiltrates and pleural effusions Dermatologist> 50% angioedema Dermographism pruritus rashes (including eczema and urticaria) Hematology> 50% Anemia lymphadenopathy splenomegaly Thromboembolic events thrombocytopenia nervous system> 50% Cerebral embolism with partial failures Diffuse encephalopathy with behavioral disorders and memory disorders and spasticity peripheral neuropathy Gastrointe stinaltrakt> 40% Abdominal cramps diarrhea nausea immunologically ? 40% Circulating immune complexes with serum sickness Increased immunoglobulin levels (particularly IgE) Occasionally, patients develop very severe eosinophilia (eg. B. eosinophil count> 100,000 / ul) complications of hyperleukocytosis as hypoxia of the brain or the lungs (z. B. encephalopathy, dyspnea or respiratory failure). Diagnostic exclusion of secondary eosinophilia studies on organ damage bone marrow examination with cytogenetic testing clarification on a hypereosinophilic syndrome should be considered when the Eosinophilenwerte are in the peripheral blood several times inexplicably at> 1500 / ul, especially when showing organ damage. Diseases that cause eosinophilia should be excluded (eosinophilia: Tests). For organ damage further determined should the blood levels (including liver enzymes, creatine kinase, and troponin kidney values) as well as EKG, echocardiography, pulmonary function tests and CT scans of the thorax, abdomen and pelvis are performed. To detect the FIP1L1 / PDGFRA fusion gene-associated and other possible causes of eosinophilia (z. B. BCR-ABL abnormalities in chronic myelogenous leukemia), should have a bone marrow aspiration aspiration and biopsy with flow cytometry, cytogenetics and reverse transcriptase-PCR or fluorescence (FISH) take place in situ hybridization. Prognosis Usually occurs death is due to organic disorder one (especially the heart). A cardiac involvement can not be predicted by the degree or duration of eosinophilia. The prognosis depends on the response to treatment. Talk to patients with FIP1L1 / PDGFRA fusion gene associated to treatment with imatinib on, the prognosis is favorable. The current treatment options have improved the prognosis. Therapy corticosteroids in hypereosinophilic and often used to treat organ damage imatinib in patients with FIP1L1 / PDGFRA-associated fusion Sometimes drugs to control Eosinophilzahl (z. B. hydroxyurea, interferon alfa, etoposide, cladribine) Supportive therapy Treatments include immediate treatment, definitive therapies (treatments of the disease) and supportive therapies. Immediate treatment in patients with very severe eosinophilia, complications of hyperleukocytosis or both (usually patients with eosinophilic leukemia) should immediately administered intravenously with high doses of corticosteroids (e.g., prednisone 1 mg / kg or equivalent) to be treated. significantly lower if the eosinophil after 24 h (. eg by ? 50%), the corticosteroids can be repeated daily; the therapy is ineffective, an alternative treatment (eg. B. Hydroxyurea) is started. Once the eosinophil begins to fall and is under better control, additional drugs started werden.Definitive therapy patients with FIP1L1 / PDGFRA fusion gene may be associated generally with imatinib and, especially in cases of suspected damage to the heart, treated with corticosteroids. When imatinib is ineffective or poorly tolerated, another tyrosine kinase inhibitor (eg. As dasatinib, nilotinib, sorafenib) may, or allogeneic hematopoietic stem cell transplantation be applied. Patients without FIP1L1 / PDGFRA fusion gene-associated often obtained even if they are asymptomatic, a dose of 60 mg of prednisone (or 1 mg / kg) p.o., to determine the effectiveness of corticosteroids (d. E. Decrease in eosinophil count). Patients with symptoms or organ damage, over 2 weeks, a constant dose prednisone, which is then tapered off. For at least 6 months, patients are monitored without symptoms and organ damage in terms of developing complications. When corticosteroids may not be tapered readily kortikosteroidsparende a drug can (z. B. hydroxyurea, interferon alpha) are used. Mepolizumab, a fully human monoclonal antibody to interleukin-5 (a regulator of Eosinophilenproduktion) is clinical trials unterzogen.Supportive Therapy A supportive drug therapy and surgery can be necessary (eg. As infiltrative cardiomyopathy, flaps lesions, heart failure) in cardiac manifestations. Thrombotic complications can make the use of antiplatelet agents required (such as aspirin, clopidogrel, ticlopidine.); anticoagulation is necessary when a left ventricular mural thrombus exists or if transient ischemic attacks persist despite administration of acetylsalicylic acid. Key points The hypereosinophilic syndrome (HES) is a peripheral blood eosinophilia (> 1500 / uL), which is not caused by parasitic, allergic or other secondary causes of eosinophilia, has continued for ? 6 months, and causes organ damage or malfunction. HES appears to be the manifestation of a variety of hematopoietic disorders, some of which have a genetic cause. Although any organ can be involved, heart, lungs, spleen, skin and nervous system are typically affected; the involvement of the heart can cause significant morbidity and mortality. Tests for determining organ involvement, including liver enzymes, creatine kinase, creatinine and troponin; EKG, echocardiography, pulmonary function tests and CT scans of the thorax, abdomen and pelvis are performed. A bone marrow examination with cytogenetic testing is performed to identify the cause. Corticosteroids are administered in severe eosinophilia and / or organ damage. Tyrosine kinase inhibitors, such as low-dose imatinib, may be helpful in subtypes that are associated with different chromosomal abnormalities.

Health Life Media Team

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