Materiały źródłowe

• #1 Hypereosinophilic Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK599558/

  Hypereosinophilic Syndrome (HES) is a rare and complex group of disorders posing diagnostic challenges for clinicians. Characterized by significant increases in eosinophil levels, HES can lead to tissue infiltration and damage. This course is designed to equip clinicians with a comprehensive understanding of the epidemiology, evaluation, and management of HES, offering valuable insights to enhance patient care. […] Throughout the course, participants will explore the diagnostic criteria for HES, emphasizing the importance of eosinophil counts, evidence of organ or tissue damage, and the exclusion of alternative causes. […] The HES criteria are as follows: Hypereosinophilia is characterized by 1.5 x 10^9 eosinophils on CBC on 2 examinations 1 month apart. The percentage of eosinophils in the bone marrow (BM) section must exceed 20% of all nucleated cells. The pathologist’s assessment that the tissue infiltration by eosinophils is extensive and/or marked deposition of eosinophil granule proteins is found. Evidence of organ or tissue damage attributable to tissue hypereosinophilia (HE). Exclusion of other disorders or conditions as major reasons for organ damage.

• #1 Hypereosinophilic Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK599558/

  Evaluation of patients presenting with eosinophilia should start with a focused history that identifies known and treatable causes. This includes screening for parasitic infections through stool testing for ova and parasites and investigating potential adverse drug reactions, including those associated with natural supplements. Subsequent steps should detect any evidence of end-organ involvement. It is crucial to remember that end-organ damage may manifest insidiously and does not always correlate with the degree of hypereosinophilia. […] In patients meeting the diagnostic criteria for HES without an identified underlying cause of eosinophilia, further investigation is warranted to delineate HES variants. Initial laboratory studies should include CBC with differential, comprehensive blood chemistries, liver enzymes, renal function tests, creatine kinase, and troponin levels. Additional diagnostic and imaging studies to initiate include electrocardiogram, echocardiogram, pulmonary function tests, chest radiography, CT of the chest and abdomen, and tissue biopsies if indicated.

• #1 Hypereosinophilic Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK599558/

  When suspecting specific variants, certain testing may provide diagnostic benefits. M-HES variants are notable for increased serum B12 and FIP1L1-PDGFRA fusion genes. Anemia, thrombocytopenia, elevated serum tryptase, and hepatosplenomegaly have been noted. L-HES presents dermatologic symptoms, although other organs may be involved. Molecular testing could reveal abnormal T cell markers, including CD3-CD4+, CD3+CD4-CD8-, and CD4+CD7-, among others. Further testing includes T cell receptor and cytogenetic studies to determine the presence of T cell clonality and rare karyotypic abnormalities. Presence or exposure to Epstein-Barr virus (EBV) should be defined since chronic infection could drive L-HES. […] Whether a patient needs treatment for HES depends on the underlying cause and disease severity. Individuals with undetermined causes of HES should undergo a comprehensive evaluation to identify treatable factors, such as drug hypersensitivity and helminth infection, and assess for M-HES associated with the FIP1L1-PDGFRA transcription gene. Therapeutic objectives include reducing the eosinophil count, improving disease symptoms, and preventing disease progression.

• #1 Hypereosinophilic syndrome – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hypereosinophilic-syndrome/diagnosis-treatment/drc-20352856

  Many types of disorders can raise your eosinophil level, including certain infections, allergies and reactions to medications. When trying to determine whether you have hypereosinophilic syndrome (HES), your doctor is likely to ask about your travel history and any medications you’re taking, to help rule out these other causes. […] Your doctor may also need information from some of the following lab tests: […] Blood tests, to detect autoimmune conditions, parasitic infections, or problems with your liver or kidneys […] Allergy tests, to detect environmental or food allergies […] Stool tests, to detect parasitic infections such as hookworm […] Genetic test, to check for a gene mutation that can cause HES. […] Imaging tests may include: […] X-rays, to check the condition of your lungs

• #1 Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and diagnosis – UpToDate

  https://www.uptodate.com/contents/hypereosinophilic-syndromes-clinical-manifestations-pathophysiology-and-diagnosis/print

  Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and diagnosis […] The clinical features, pathophysiology, and diagnosis of HES will be reviewed here. […] Hypereosinophilia (HE) is defined as an absolute eosinophil count (AEC) >1.5 x 10^9/L (or >1500 cells/microL) in the peripheral blood on two examinations separated in time by at least one month and/or pathologic confirmation of tissue HE.

• #1 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  After a thorough workup has excluded causes for secondary eosinophilia, a diagnosis of hypereosinophilic syndrome is suspected in cases of persistent eosinophilia. Any such patients with a documented absolute eosinophil count (AEC) greater than 1500/L on at least two occasions should be evaluated for hypereosinophilic syndrome, regardless of the presence of symptoms. […] A complete blood cell (CBC) count and peripheral smear is warranted. […] Serum tryptase levels are elevated in FIP1LI-PDGFRApositive hypereosinophilic syndrome, as well as systemic mastocytosis with chronic eosinophilic leukemia (SM-CEL). Hence, in such cases, the workup should include the following: Bone marrow tryptase levels, Immunophenotyping of mast cells, Molecular genetic studies to detect FIP1L1-PDGFRA mutation and C-KIT mutation are done to determine imatinib sensitivity.

• #1 Managing Patients with Hypereosinophilic Syndrome: A Statement from the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC)

  https://www.mdpi.com/2073-4409/13/14/1180

  The initial assessment includes a consideration of family, as familial HE (HEFA) is possible, although rare. […] The presence or absence of a reactive process is established based on clinical and laboratory features. […] If HER is confirmed, efforts are directed towards identifying the specific disease process causing HE (inflammation, infection, tumor, and drug hypersensitivity). […] When primary clonal HE (HEN) is detected, it is crucial to determine the underlying hematological neoplasm according to the latest WHO and ICC classifications. […] The patients without an underlying reactive condition and no sign of clonality are provisionally diagnosed with HEUS. […] These patients must be carefully monitored over time, especially for the presence of organ involvement. […] Finally, the investigation is extended to assess organ involvement, and the patients with HE-related organ damage are diagnosed with HES.

• #1 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  Eosinophilia is present ( 1500 cells/L). […] Echocardiography is helpful in the initial evaluation and monitoring of cardiac disease in patients suspected with hypereosinophilic syndrome. […] An endocardial biopsy may be performed via cardiac catheterization if any question about the diagnosis of hypereosinophilic syndrome exists. […] Perform bone marrow aspiration and biopsy, and submit samples for cytogenetic studies. […] Eosinophil infiltrates are present in affected tissues in patients with hypereosinophilic syndrome.

• #1 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  Bone marrow biopsy should be evaluated for the following: Morphologic examinations to look for features of myeloproliferative disorders (MPDs) and to look for dense aggregates of mast cells, Special stains should include reticulin stain for myelofibrosis and tryptase staining for mast cells when serum tryptase levels are elevated, Cytogenetics: Most patients with hypereosinophilic syndrome have normal karyotypes; in those who have cytogenetic changes, the changes may vary from aneuploidy to Philadelphia chromosome, Molecular genetic studies: FIP1L1/PDGFRA should be evaluated in all patients with increased tryptase levels; this mutation is present in both hypereosinophilic syndrome and systemic mastocytosis; C-KIT mutation should also be evaluated in patients with increased tryptase levels.

• #1 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  Human leukocyte antigen (HLA) typing should be done early in the course of hypereosinophilic syndrome for patients with aggressive disease, cytogenetic aberration, or the FIPL1/PDGFRA fusion gene. […] Initial evaluation of suspected hypereosinophilic syndrome should include tests to look for any evidence of end-organ damage. […] Wang has proposed an algorithm for the workup of patients with hypereosinophilia. […] Increased serum tryptase level suggests a FIP1L1-PDGFRA mutation; always rule out C-KIT mutation, which is characteristic of systemic mastocytosis whenever serum tryptase is elevated. […] Interleukin-5 (IL-5) levels are elevated in cases of hypereosinophilic syndrome that are associated with clonal T-cell disease. […] Immunoglobulin E (IgE) levels may be elevated, and hypergammaglobulinemia is common; increased IgE levels have prognostic significance.

• #1 Hypereosinophilic Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK599558/

  In cases of clinically stable HES, when the decision to proceed with treatment is established, the initial approach should be guided by the variant of HES. Systemic glucocorticoids serve as the primary line of therapy for most HES variants. According to a multicenter retrospective analysis of 188 HES patients, 85% achieved partial or complete symptom remission within 1 month, and maintenance therapy was sustained for a minimum of 2 months to a maximum of 20 years. […] Patients displaying resistance to steroids should be re-evaluated and initiated on imatinib. In instances of secondary HES, treatment should be directed at addressing the underlying cause.

• #1 Hypereosinophilic Syndrome

  https://www.aaaai.org/conditions-treatments/related-conditions/hypereosinophilic-syndrome

  Most people have less than 500 eosinophils/microliter in their blood. People with HES usually have more than 1,500 eosinophils/microliter in their blood for 6 months or more, and the cause cannot be identified. […] Diagnosis Symptoms of HES are also common in many other medical problems, making an initial diagnosis more difficult. The first step is to rule out other conditions with similar symptoms. These include parasitic infection, allergic disease, cancers, autoimmune diseases and drug reactions. […] An allergist / immunologist has specialized training to effectively diagnose the problem and, if HES is present, to work collaboratively with other specialists such as a hematologist or cardiologist in the treatment and monitoring of HES. […] Testing is individualized according to symptoms and may include stool evaluation to detect parasitic infection, allergy testing to diagnose environmental or food allergies, biopsies of the skin or other organs, blood tests to screen for autoimmunity or CT imaging of affected organs, molecular genetic studies to detect FIP1L1-PDGFRA or other mutations to help determine, diagnosis, prognosis, and treatment.

• #1 How I Diagnose Hypereosinophilic Syndromes – European Medical Journal

  https://www.emjreviews.com/hematology/article/how-i-diagnose-hypereosinophilic-syndromes/

  Hypereosinophilic syndromes are a group of disorders characterised by significant eosinophilia and organ damage. They have proven challenging to define, diagnose, and study for many years, due in part to their variable clinical presentations, the overlap between neoplastic and reactive eosinophilia, and the lack of a universal marker of eosinophil clonality. Herein, we give an overview of the term and discuss aetiology and our approach to diagnosis. […] HES are defined by the presence of organ dysfunction. Our first aim in assessing a patient with HE is to identify organ dysfunction as this allows appropriate classification and facilitates treatment. Our second aim is to identify the underlying cause. The clinical history and examination findings play a key role in guiding specific investigations. An overview to our approach is provided in Figure 1.

• #2 Hypereosinophilic Syndrome | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/149474

  Hypereosinophilic syndrome (HES) encompasses a rare and complex group of heterogeneous disorders characterized by persistent and substantial elevations in eosinophil levels and mediators leading to tissue infiltration and damage. […] The HES criteria are as follows: Hypereosinophilia is characterized by 1.5 x 10^9 eosinophils on CBC on 2 examinations 1 month apart. The percentage of eosinophils in the bone marrow (BM) section must exceed 20% of all nucleated cells. The pathologist’s assessment that the tissue infiltration by eosinophils is extensive and/or marked deposition of eosinophil granule proteins is found. Evidence of organ or tissue damage attributable to tissue hypereosinophilia (HE). Exclusion of other disorders or conditions as major reasons for organ damage. […] Evaluation of patients presenting with eosinophilia should start with a focused history that identifies known and treatable causes. This includes screening for parasitic infections through stool testing for ova and parasites and investigating potential adverse drug reactions, including those associated with natural supplements. Subsequent steps should detect any evidence of end-organ involvement. It is crucial to remember that end-organ damage may manifest insidiously and does not always correlate with the degree of hypereosinophilia.

• #2 Hypereosinophilic Syndrome

  https://www.aaaai.org/conditions-treatments/related-conditions/hypereosinophilic-syndrome

  Most people have less than 500 eosinophils/microliter in their blood. People with HES usually have more than 1,500 eosinophils/microliter in their blood for 6 months or more, and the cause cannot be identified. […] Diagnosis Symptoms of HES are also common in many other medical problems, making an initial diagnosis more difficult. The first step is to rule out other conditions with similar symptoms. These include parasitic infection, allergic disease, cancers, autoimmune diseases and drug reactions. […] An allergist / immunologist has specialized training to effectively diagnose the problem and, if HES is present, to work collaboratively with other specialists such as a hematologist or cardiologist in the treatment and monitoring of HES. […] Testing is individualized according to symptoms and may include stool evaluation to detect parasitic infection, allergy testing to diagnose environmental or food allergies, biopsies of the skin or other organs, blood tests to screen for autoimmunity or CT imaging of affected organs, molecular genetic studies to detect FIP1L1-PDGFRA or other mutations to help determine, diagnosis, prognosis, and treatment.

• #2 Eosinophilic disorders: evaluation of current classification and diagnostic criteria, proposal of a practical diagnostic algorithm | Clinical and Translational Allergy | Full Text

  https://ctajournal.biomedcentral.com/articles/10.1186/s13601-019-0277-4

  Taking into consideration a step by step approach of hypereosinophilia in clinical practice and the main laboratory tests used for a comprehensive evaluation, a proposal of a diagnosis algorithm of HES is showed in Fig. 1. […] The evaluation of a patient with eosinophilia may be complex, costly, needs time and a multidisciplinary approach. […] There is a clear need for harmonization of terminology and classification of eosinophilic disorders and for better quantification of HE-related end-organ damage. […] Despite remarkable progress in understanding pathophysiologic mechanisms of eosinophilic disorders, there are still many unclear aspects, confusing terminology and gaps in diagnosing this very heterogeneous group of diseases.

• #2 Hypereosinophilic syndrome – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hypereosinophilic-syndrome/diagnosis-treatment/drc-20352856

  Many types of disorders can raise your eosinophil level, including certain infections, allergies and reactions to medications. When trying to determine whether you have hypereosinophilic syndrome (HES), your doctor is likely to ask about your travel history and any medications you’re taking, to help rule out these other causes. […] Your doctor may also need information from some of the following lab tests: […] Blood tests, to detect autoimmune conditions, parasitic infections, or problems with your liver or kidneys […] Allergy tests, to detect environmental or food allergies […] Stool tests, to detect parasitic infections such as hookworm […] Genetic test, to check for a gene mutation that can cause HES. […] Imaging tests may include: […] X-rays, to check the condition of your lungs

• #2 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  After a thorough workup has excluded causes for secondary eosinophilia, a diagnosis of hypereosinophilic syndrome is suspected in cases of persistent eosinophilia. Any such patients with a documented absolute eosinophil count (AEC) greater than 1500/L on at least two occasions should be evaluated for hypereosinophilic syndrome, regardless of the presence of symptoms. […] A complete blood cell (CBC) count and peripheral smear is warranted. […] Serum tryptase levels are elevated in FIP1LI-PDGFRApositive hypereosinophilic syndrome, as well as systemic mastocytosis with chronic eosinophilic leukemia (SM-CEL). Hence, in such cases, the workup should include the following: Bone marrow tryptase levels, Immunophenotyping of mast cells, Molecular genetic studies to detect FIP1L1-PDGFRA mutation and C-KIT mutation are done to determine imatinib sensitivity.

• #2 Hypereosinophilic syndrome – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hypereosinophilic-syndrome/diagnosis-treatment/drc-20352856

  CT scan, to detect problems in the chest, abdomen and pelvis […] Echocardiogram or MRI, to assess heart function. […] Treatment for hypereosinophilic syndrome is aimed at reducing your eosinophil count to prevent tissue damage, especially to your heart. Specific treatment depends on your symptoms, the severity of your condition and the cause of your HES. […] For hypereosinophilic syndrome, some basic questions to ask the doctor include: […] Will I need additional tests? […] What are the treatment options? […] What are the benefits and risks of each treatment? […] Should I see additional specialists? What will that cost, and will my insurance cover it? […] Are there brochures or other printed material that I can have? What websites do you recommend? […] The doctor is likely to ask you several questions. Be ready to answer them to allow time later to cover other points you want to address. Examples include: […] Have you traveled out of the country lately? […] Do you have any allergies or skin conditions? […] Have you been exposed to any parasites such as hookworm?

• #2 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  Bone marrow biopsy should be evaluated for the following: Morphologic examinations to look for features of myeloproliferative disorders (MPDs) and to look for dense aggregates of mast cells, Special stains should include reticulin stain for myelofibrosis and tryptase staining for mast cells when serum tryptase levels are elevated, Cytogenetics: Most patients with hypereosinophilic syndrome have normal karyotypes; in those who have cytogenetic changes, the changes may vary from aneuploidy to Philadelphia chromosome, Molecular genetic studies: FIP1L1/PDGFRA should be evaluated in all patients with increased tryptase levels; this mutation is present in both hypereosinophilic syndrome and systemic mastocytosis; C-KIT mutation should also be evaluated in patients with increased tryptase levels.

• #2

  https://www.haematologica.org/article/view/5338

  Hence, doses below 100 mg daily are not recommended, and some authors even recommend higher dosing if treatment is well tolerated. […] In practical terms, the ideal dose of imatinib in a given patient is that required to induce and maintain molecular remission. […] Although eosinophil levels generally plummet within days in patients with PDGFRA rearrangements, disappearance of the molecular defect generally takes several months. […] It has now become common practice to perform T-cell phenotyping and to investigate TCR gene rearrangements on peripheral blood and, eventually, on bone marrow in patients with HES in order to identify those with L-HES. […] Given this, the conclusion can be drawn that formal diagnosis of L-HES currently requires careful T-cell phenotyping and PCR analysis of TCR gene rearrangements, ideally in conjunction with assessment of cytokine production by cultured PBMC or T cells.

• #2 Hypereosinophilic Syndrome: Symptoms, Diagnosis, Treatment, and More

  https://www.healthline.com/health/hypereosinophilic-syndrome

  If a healthcare professional suspects you may have HES, theyll start with ordering a blood test to measure your eosinophil levels if this hasnt already been done. […] HES involves elevated levels of eosinophils over a long period of time, typically 6 months or longer. The average person has fewer than 500 eosinophils per milliliter (mL) of blood. In people with HES, eosinophil levels tend to be greater than 1,500 eosinophils/mL. […] Next, your care team will want to rule out other causes of high levels of eosinophils, such as: viral, bacterial, or parasitic infection, allergic disease, drug/chemical reactions, autoimmune disease, hypoadrenalism, abnormal tissue growth or cancer. […] Ruling out the above will likely involve additional testing, including allergy testing, more blood tests, or fecal exams. All these potential causes come with their own set of tests.

• #2 How I Diagnose Hypereosinophilic Syndromes – European Medical Journal

  https://www.emjreviews.com/hematology/article/how-i-diagnose-hypereosinophilic-syndromes/

  We use an eosinophil count 1.5109/L on at least two occasions 1 month apart to define HE. In the absence of organ damage we take a stepwise approach to diagnosis, attempting to exclude secondary causes before investigating neoplastic processes. If organ damage is identified, we typically investigate primary and secondary causes of HES simultaneously to hasten diagnosis, allow specific therapy, and minimise further tissue damage. […] Investigation for organ dysfunction should be guided by clinical history. In asymptomatic patients with incidental HE we typically defer such investigation. In symptomatic patients, we perform investigations targeting the involved organ system(s). […] Blood counts and morphological review of the blood film are essential to diagnosis. Blood film review may identify abnormalities, including dysplastic eosinophils, to suggest primary HES.

• #2 Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and diagnosis – UpToDate

  https://www.uptodate.com/contents/hypereosinophilic-syndromes-clinical-manifestations-pathophysiology-and-diagnosis

  Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and diagnosis […] The clinical features, pathophysiology, and diagnosis of HES will be reviewed here. […] Diagnosis of HES subtypes […] Diagnosis of myeloproliferative variants […] Diagnosis of L-HES […] Diagnosis of familial HES […] Diagnosis of organ-restricted HES […] Diagnosis of specific defined syndromes associated with HE […] Diagnosis of hypereosinophilia of undetermined significance.

• #2 Hypereosinophilic Syndrome and T-Cell Lymphoma: Which Comes First? | Actas Dermo-Sifiliográficas

  https://actasdermo.org/es-hypereosinophilic-syndrome-t-cell-lymphoma-articulo-S0001731023005902

  Hypereosinophilic syndrome (HES) is defined by a concentration of eosinophils in peripheral blood greater than 1500cells/L, accompanied by organ damage or dysfunction not attributable to other causes. […] HESs include the lymphoproliferative form (L-HES), in which there is an abnormal T-cell (TC) population in peripheral blood, with clonal rearrangement of the TC receptors (TCRs). These produce eosinophil-derived cytokines. Therefore, unlike the clonal myeloproliferative variant, L-HES is a mixture of a clonal process (TC clones) and a reactive one (eosinophilia derived from the secretion of cytokines from these TCs). […] Close follow-up of these patients is essential, as 10-20% may progress to cutaneous T-cell lymphoma (CTCL) with a poor prognosis. It is important to distinguish between the 2 entities, given the indolent course in the case of patients with L-HES compared with the worse prognosis in CTCL.

• #2 Hypereosinophilic syndrome

  https://dermnetnz.org/topics/hypereosinophilic-syndrome

  An elevated peripheral blood eosinophil count is found on a full blood count test. […] A skin biopsy often reveals an infiltrate of eosinophils.

• #2 Hypereosinophilic syndromes | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-37

  Classification of HES patients remains difficult in a routine setting, and requires referral of blood and/or marrow samples to qualified laboratories for optimal evaluation. […] At the present time, standard care demands that the three following tests be performed on peripheral blood and/or bone marrow for all patients: search for the F/P fusion gene using RT-PCR (reverse transcription polymerase chain reaction, preferably nested for increased sensitivity) and/or FISH (fluorescent in situ hybridisation) for the CHIC2 locus (absence of this locus is considered a surrogate marker for presence of the F/P fusion), lymphocyte phenotyping, and analysis of T cell receptor (TCR) gene rearrangement patterns. […] However, despite adherence to the preceding guidelines, a number of patients will remain unclassified. Additional investigations in a research setting that may help distinguish myeloid and lymphoid disorders include: analysis of cytokine profiles of T cell subsets including eosinophilopoietic (IL-3 and GM-CSF) and/or type 2 (IL-4, IL-5, IL-13) cytokines, measurement of serum tryptase and TARC levels, and cytogenetic analysis focusing on imatinib target tyrosine kinases.

• #2 Hypereosinophilic syndrome (Idiopathic hypereosinophilic syndrome) – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/hypereosinophilic-syndrome-idiopathic-hypereosinophilic-syndrome/

  The primary goal of treatment of HES is to decrease tissue eosinophilia and reduce eosinophil-associated damage to the tissue. Peripheral eosinophilia is a readily available laboratory value; however, it does not reliably predict the degree of tissue damage. In the absence of a reliable and validated biomarker, patients should be clinically followed closely. Serial echocardiograms are recommended every 6-12 months, particularly in M-HES, since cardiac involvement may be asymptomatic. Depending on clinical presentation, skin biopsy, pulmonary function test, scan imaging of chest or abdomen may be considered in follow up of patients. […] A crucial step in management of patients suspected to have HES is to exclude the secondary causes of eosinophilia that require specific treatment not directed towards eosinophilia. Parasitic infestations, most importantly strongyloidosis, should be excluded by an enzyme-linked immunsorbant assay in all patients with plausible history of exposure. Treating with corticosteroids can lead to fatal dissemination of this parasite.

• #2 Hypereosinophilic Syndromes – Apfed

  https://apfed.org/about-ead/hypereosinophilic-syndrome/

  Hypereosinophilic Syndromes (HES) are a group of rare disorders in which high numbers of eosinophils are found in the blood and tissue, for prolonged period of time (6 months or more) for which a cause cannot be found. […] The symptoms of HES are also common in many other medical problems, including autoimmune diseases, allergic disease, cancer, and drug reactions, making HES more difficult to diagnose. […] Since many different problems can cause high numbers of eosinophils in the blood, higher than normal blood eosinophil number alone does not mean an individual has, or will develop, HES. […] Criteria has been developed that must be fulfilled for an individual to be diagnosed with HES. […] Tests are needed to diagnose HES and include a complete blood cell count, including eosinophil count, blood samples for liver and kidney function, and blood tests for Vitamin B12 and tryptase. […] A bone marrow biopsy is recommended in patients suspected of having HES. […] The disease may be diagnosed and monitored by a team of specialists, such as allergist/immunologist, hematologist, and/or cardiologist.

• #2 Hypereosinophilic Syndrome (HES): Types, Symptoms, & More

  https://www.health.com/hypereosinophilic-syndrome-8546797

  Diagnosing hypereosinophilic syndrome can be a challenge because the symptoms are similar to those in other conditions, such as autoimmune disorders and allergic reactions. Typically, a multi-step approach is taken to rule out other possible causes of your symptoms before diagnosing HES. […] Diagnostic tests help provide an accurate diagnosis and determine the underlying cause of HES. Depending on your symptoms, they may order: […] Blood tests to measure your complete blood cell count (CBC) and eosinophil count. Blood tests can also measure substances that monitor liver and kidney function, vitamin B12, and tryptase levels (an enzyme that contributes to allergic reactions). […] Imaging scans, such as X-rays, computed tomography (CT) scans, and ultrasounds, allow your healthcare provider to view your internal organs to check for damage. A chest X-ray, for example, can show lung damage, and an echocardiogram (ultrasound) shows how your heart is functioning.

• #3 Orphanet: Hypereosinophilic syndrome

  https://www.orpha.net/en/disease/detail/168956

  Hypereosinophilic syndrome (HES) constitutes a rare and heterogeneous group of disorders, defined as persistent and marked blood eosinophilia and/or tissue eosinophilia associated with a wide range of clinical manifestations reflecting eosinophil-induced tissue/organ damage. […] Diagnosis of HES relies on the observation of persistent and marked HE ( 1.5 109/L) and /or eosinophilic infiltration of tissue(s) responsible for target-organ damage. Once these criteria are fulfilled, further testing for eventual pathogenic classification is warranted using appropriate cytogenetic, phenotypic, and functional approaches. If underlying causes of HE have been excluded, the term idiopathic HES is appropriate.

• #3 Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and diagnosis – UpToDate

  https://www.uptodate.com/contents/hypereosinophilic-syndromes-clinical-manifestations-pathophysiology-and-diagnosis/print

  Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and diagnosis […] The clinical features, pathophysiology, and diagnosis of HES will be reviewed here. […] Hypereosinophilia (HE) is defined as an absolute eosinophil count (AEC) >1.5 x 10^9/L (or >1500 cells/microL) in the peripheral blood on two examinations separated in time by at least one month and/or pathologic confirmation of tissue HE.

• #3 Eosinophilia: Definition, Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17710-eosinophilia

  Healthcare providers typically discover eosinophilia during a routine blood test called a complete blood count (CBC) with a differential white blood cell count. […] Depending on your situation, your healthcare provider may do more tests to find out why your eosinophil levels are higher than normal. […] Healthcare providers treat the underlying condition or issue that’s causing high eosinophil counts. […] If you have high eosinophil levels because you have allergies or chronic sinusitis, your healthcare provider may recommend allergy testing to find out what causes the allergic reaction that triggered eosinophilia. […] If there’s a blood cancer, your healthcare provider will treat it.

• #3 Hypereosinophilic Syndrome | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/149474

  In patients meeting the diagnostic criteria for HES without an identified underlying cause of eosinophilia, further investigation is warranted to delineate HES variants. Initial laboratory studies should include CBC with differential, comprehensive blood chemistries, liver enzymes, renal function tests, creatine kinase, and troponin levels. Additional diagnostic and imaging studies to initiate include electrocardiogram, echocardiogram, pulmonary function tests, chest radiography, CT of the chest and abdomen, and tissue biopsies if indicated. […] When suspecting specific variants, certain testing may provide diagnostic benefits. M-HES variants are notable for increased serum B12 and FIP1L1-PDGFRA fusion genes. Anemia, thrombocytopenia, elevated serum tryptase, and hepatosplenomegaly have been noted. L-HES presents dermatologic symptoms, although other organs may be involved.

• #3 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  Human leukocyte antigen (HLA) typing should be done early in the course of hypereosinophilic syndrome for patients with aggressive disease, cytogenetic aberration, or the FIPL1/PDGFRA fusion gene. […] Initial evaluation of suspected hypereosinophilic syndrome should include tests to look for any evidence of end-organ damage. […] Wang has proposed an algorithm for the workup of patients with hypereosinophilia. […] Increased serum tryptase level suggests a FIP1L1-PDGFRA mutation; always rule out C-KIT mutation, which is characteristic of systemic mastocytosis whenever serum tryptase is elevated. […] Interleukin-5 (IL-5) levels are elevated in cases of hypereosinophilic syndrome that are associated with clonal T-cell disease. […] Immunoglobulin E (IgE) levels may be elevated, and hypergammaglobulinemia is common; increased IgE levels have prognostic significance.

• #3 How I Diagnose Hypereosinophilic Syndromes – European Medical Journal

  https://www.emjreviews.com/hematology/article/how-i-diagnose-hypereosinophilic-syndromes/

  T cell receptor (TCR) gene rearrangement studies have been increasingly used in the setting of eosinophilia to investigate T cell clonality and lymphocyte-variant HES. Clonal rearrangements are common, with one study finding 18 out of 42 (42.8%) patients to have TCR clonality. […] Myeloid/lymphoid neoplasms with eosinophilia and recurrent genetic rearrangements should be specifically excluded. The majority of these cases have a cryptic deletion of chromosome 4q12 creating the FIP1L1-PDGFRA fusion gene.

• #3 Hypereosinophilic syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Hypereosinophilic_syndrome

  Hypereosinophilic syndrome is a disease characterized by a persistently elevated eosinophil count (1500 eosinophils/mm) in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow. […] HES is a diagnosis of exclusion, after clonal eosinophilia (such as FIP1L1-PDGFRA-fusion induced hypereosinophelia and leukemia) and reactive eosinophilia (in response to infection, autoimmune disease, atopy, hypoadrenalism, tropical eosinophilia, or cancer) have been ruled out. […] Numerous techniques are used to diagnose hypereosinophilic syndrome, of which the most important is blood testing. In HES, the eosinophil count is greater than 1.5 109/L. […] Since there isn’t a particular diagnostic test for HES, the syndrome is diagnosed by exclusion. […] Differential diagnosis includes drug hypersensitivity reactions, parasitic infections, sarcoid, advanced HIV infection, inflammatory bowel disease, lymphoid neoplasms, and autoimmune lymphoproliferative syndrome.

• #3

  https://link.springer.com/article/10.1007/s40629-022-00221-w

  Sustained elevation of eosinophils above 5109/l in peripheral blood (PB) should prompt further investigation. […] The diagnosis of HES is made when organ infiltration with consecutive dysfunction is diagnosed in persistent eosinophilia after exclusion of other causes. […] Causes of reactive eosinophilia can be clarified in many cases by anamnesis (drugs, allergies, solid tumors, lymphomas). […] The most important differential diagnosis to HES is clonal eosinophilia. […] HES is a diagnosis of exclusion and should be made only after reactive and clonal eosinophilia have been excluded. […] For adequate treatment of HES, careful clarification of the qualitative and quantitative organ involvement pattern is essential. […] The prognosis of HES also depends on the type and extent of organ involvement. […] Due to potentially vital threatening organ involvement and the potentially good treatability, a persistent eosinophilia above 0.5109/l should always be subjected to further evaluation.

• #3 Hypereosinophilic Syndrome Presenting As an Unusual Triad of Eosinophilia, Severe Thrombocytopenia, and Diffuse Arterial Thromboses, With Good Response to Mepolizumab – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/may-2013/hypereosinophilic-syndrome-presenting-as-an-unusual-triad-of-eosinophilia-severe-thrombocytopenia-and-diffuse-arterial-thromboses-with-good-response-to-mepolizumab/

  The lack of a readily apparent cause of reactive eosinophilia should raise concern for clonal eosinophilic proliferations. […] Evaluation for these should include a careful review of the PBS, measurement of serum tryptase (for evidence of underlying myeloid malignancies), IL-5, bone marrow biopsy, screening for FIP1L1-PDGFRA rearrangement (if positive, a working diagnosis of FIP1L1-PDGFRA–associated neoplasm is made), cytogenetic studies (in search of clonal eosinophilia mutations), and peripheral blood lymphocyte phenotyping and T-cell receptor gene rearrangement studies (to exclude lymphocytic-variant hypereosinophilia). […] The presence of severe thrombocytopenia and diffuse arterial thrombosis with eosinophilia is infrequent. […] The small subset of patients with idiopathic HES may represent the clinically overlooked reactive causes, or cases with unique molecular genetic abnormalities that remain undiscovered. […] Currently, corticosteroids are administered as first-line therapy in all patients without the FIP1L1-PDGFRA mutation.

• #3 Hypereosinophilic Syndromes (HES) | National Jewish Health

  https://www.nationaljewish.org/conditions/hypereosinophilic-syndromes

  Hypereosinophilic syndromes (HES) are types of disorders that happen when eosinophils (white blood cells) are overproduced by a persons body. […] In these cases, the diagnosis is called idiopathic (unknown) hypereosinophilic syndrome. […] Hypereosinophilic Syndromes: Diagnosis

• #3 Pathology Outlines – Idiopathic hypereosinophilic syndrome

  https://www.pathologyoutlines.com/topic/myeloproliferativehypereosinophilicsyndrome.html

  Idiopathic hypereosinophilic syndrome is a disorder defined by peripheral blood eosinophilia (absolute eosinophil count ≥ 1.5 x 10^9/L) for at least 6 months with organ damage / dysfunction attributable to tissue hypereosinophilic infiltrate per biopsy and no discernible underlying etiology. […] Diagnosis of exclusion. […] Unexplained eosinophilia of ≥ 1.5 x 10^9/L for at least 6 months that leads to tissue damage. […] Exclude reactive causes of eosinophilia (parasites, drug related, allergy, etc.). […] Exclude acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes, myelodysplastic / myeloproliferative neoplasms and systemic mastocytosis. […] Tissue damage present due to hypereosinophilia. […] Bone marrow with increased eosinophilic precursors; proposed criteria of ≥ 20% marrow cellularity with or without peripheral blood eosinophilia. […] Affected organs may have increased eosinophils with eosinophil degranulation.

• #3 Hypereosinophilic syndrome: cardiac diagnosis and management | Heart

  https://heart.bmj.com/content/102/2/100.short

  Hypereosinophilic syndrome (HES) is a heterogeneous group of conditions that is defined at its core by hypereosinophilia (HE) (blood eosinophil count of 1.5109/L) and organ damage directly attributable to the HE. […] Once a significantly elevated eosinophil count is identified, it must be confirmed on repeat testing and the aetiology for the HE must be rigorously sought out with a focus on identifying whether organ dysfunction is occurring. […] Echocardiography is routinely performed to assess for cardiac involvement, looking for evidence of left ventricular and/or right ventricular apical obliteration or thrombi or a restrictive cardiomyopathy. […] Cardiac magnetic resonance imaging and CT are often useful adjuncts to establish the diagnosis but endomyocardial biopsy remains the gold standard. […] To decrease the degree of eosinophilia, treatment can include corticosteroids and/or imatinib based on the aetiology. Anticoagulation, standard heart failure therapy for a restrictive cardiomyopathy and finally cardiac transplantation may be indicated in the treatment algorithm.

• #3

  https://www.haematologica.org/article/view/5338

  Early detection of FIP1L1-PDGFRA in patients with chronic unexplained hypereosiniphilia is now considered critical for optimal management, as its presence is associated with high spontaneous morbidity and mortality rates, and imatinib represents an extremely efficacious and generally well-tolerated first-line therapeutic agent for this condition. […] Thus, PCR for fusion gene detection and FISH for demonstration of CHIC2 deletion are becoming increasingly available in many specialized centers. […] Given the poor prognosis of FIP1L1-PDGFRA associated disease, treatment with imatinib is recommended even in the absence of clinical complications at the time the mutation is discovered; i.e. for the rare patients with still asymptomatic hypereosinophilia. […] There is some debate on the optimal dosing regimen, since doses as low as 100 mg once weekly have been shown to maintain clinical and molecular remission.

• #3 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  After a thorough workup has excluded causes for secondary eosinophilia, a diagnosis of hypereosinophilic syndrome is suspected in cases of persistent eosinophilia. Any such patients with a documented absolute eosinophil count (AEC) greater than 1500/L on at least two occasions should be evaluated for hypereosinophilic syndrome, regardless of the presence of symptoms. […] A complete blood cell (CBC) count and peripheral smear is warranted. […] Serum tryptase levels are elevated in FIP1LI-PDGFRApositive hypereosinophilic syndrome, as well as systemic mastocytosis with chronic eosinophilic leukemia (SM-CEL). Hence, in such cases, the workup should include the following: Bone marrow tryptase levels, Immunophenotyping of mast cells, Molecular genetic studies to detect FIP1L1-PDGFRA mutation and C-KIT mutation are done to determine imatinib sensitivity.

• #3 Eosinophil Counts in Hypereosinophilic Syndrome (HES)

  https://eosinophilosophy.com/disease-state/hes/

  Differentiating between HES and eosinophilic granulomatosis with polyangiitis (EGPA) is challenging; both conditions have persistent eosinophilia and systemic manifestations. […] Differentiating between HES and single organ-restricted disease can be challenging. The magnitude of blood eosinophilia, with a combination of clinical and laboratory results, and pathologic and radiographic findings may be useful for differentiating HES from single-organ disease including (but not limited to): Eosinophilic esophagitis, Eosinophilic pneumonia, Severe eosinophilic asthma. […] Eosinophil counts can help guide treatment decisions. […] Per the World Health Organizations 2019 update on eosinophilic disorders, the goal of therapy in patients with hypereosinophilia is to mitigate eosinophil-mediated organ damage.

• #3

  https://education.eaaci.org/products/diagnosis-and-assessment-of-hypereosinophilic-syndrome-hes

  This webcast is a 4-part series. The topics focus on HES pathophysiology, HES diagnosis and differential diagnosis, HES complications, and HES multidisciplinary assessment. […] discuss how to investigate HES and differentiate it from other diseases; highlight the complications, signs and symptoms that may be associated with HES; and provide clinical insight on the importance of a multidisciplinary approach for personalised assessment and treatment for patients with HES. […] the diagnosis of HES and identifying the cause, how to rule out other disease when diagnosing HES and identify current markers for HES variants.

• #4 Hypereosinophilic Syndromes (HES) Diagnosis

  https://www.nationaljewish.org/conditions/hypereosinophilic-syndromes/diagnosis

  Test results will be reviewed by the doctor to decide if the condition is in fact HES. […] These criteria are: […] Eosinophil count in the blood greater than or equal to 1500/microliter, and lasting for more than 6 months […] Signs and/or symptoms of organs not working properly due to white blood cells attacking the organs, and […] No other apparent explanations for the increased white blood cells, such as parasitic infection or allergic disease. If vital organs like the heart or bone marrow are not working properly and its happening quickly, a doctor will not wait 6 months before diagnosing and considering prompt treatment for the HES.

• #4 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Eosinophilia-Tests-and-Diagnosis.aspx

  Eosinophilia refers to an absolute peripheral blood eosinophil count of over 500/L. With such a finding, a step-by-step diagnostic evaluation is required. […] The patient should have a detailed examination of the cardiovascular, renal, respiratory, gastrointestinal, and neurologic systems. Such findings as a skin rash, asthma or lung congestion, or generalized lymphadenopathy are suspicious of underlying conditions such as pulmonary syndromes with eosinophilia, myeloproliferative disorders, and vasculitis or atopic disease. This examination will also help to pick up complications due to hypereosinophilia, the most important of which include pulmonary, neurologic, and cardiac dysfunction. […] If no cause is found after full testing, the patient needs to be evaluated for possible hypereosinophilia syndromes (HES). This testing may include: RT-PCR and FISH for presence of the F/P fusion, T cell receptor (TCR) phenotyping, PCR for TCR gene rearrangement, karyotyping. […] For most HES, an initial course of corticosteroids is advised, with hydroxyurea or interferon- being added as corticosteroid-sparing agents if long-term steroid therapy is required. Imatinibmesylate is first-line therapy for some types of HES.

• #4 Hypereosinophilic Syndrome: Symptoms, Diagnosis, Treatment, and More

  https://www.healthline.com/health/hypereosinophilic-syndrome

  If a healthcare professional suspects you may have HES, theyll start with ordering a blood test to measure your eosinophil levels if this hasnt already been done. […] HES involves elevated levels of eosinophils over a long period of time, typically 6 months or longer. The average person has fewer than 500 eosinophils per milliliter (mL) of blood. In people with HES, eosinophil levels tend to be greater than 1,500 eosinophils/mL. […] Next, your care team will want to rule out other causes of high levels of eosinophils, such as: viral, bacterial, or parasitic infection, allergic disease, drug/chemical reactions, autoimmune disease, hypoadrenalism, abnormal tissue growth or cancer. […] Ruling out the above will likely involve additional testing, including allergy testing, more blood tests, or fecal exams. All these potential causes come with their own set of tests.

• #4 Hypereosinophilic Syndrome (HES): Types, Symptoms, & More

  https://www.health.com/hypereosinophilic-syndrome-8546797

  Diagnosing hypereosinophilic syndrome can be a challenge because the symptoms are similar to those in other conditions, such as autoimmune disorders and allergic reactions. Typically, a multi-step approach is taken to rule out other possible causes of your symptoms before diagnosing HES. […] Diagnostic tests help provide an accurate diagnosis and determine the underlying cause of HES. Depending on your symptoms, they may order: […] Blood tests to measure your complete blood cell count (CBC) and eosinophil count. Blood tests can also measure substances that monitor liver and kidney function, vitamin B12, and tryptase levels (an enzyme that contributes to allergic reactions). […] Imaging scans, such as X-rays, computed tomography (CT) scans, and ultrasounds, allow your healthcare provider to view your internal organs to check for damage. A chest X-ray, for example, can show lung damage, and an echocardiogram (ultrasound) shows how your heart is functioning.

• #4 Hypereosinophilic Syndrome | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/149474

  In patients meeting the diagnostic criteria for HES without an identified underlying cause of eosinophilia, further investigation is warranted to delineate HES variants. Initial laboratory studies should include CBC with differential, comprehensive blood chemistries, liver enzymes, renal function tests, creatine kinase, and troponin levels. Additional diagnostic and imaging studies to initiate include electrocardiogram, echocardiogram, pulmonary function tests, chest radiography, CT of the chest and abdomen, and tissue biopsies if indicated. […] When suspecting specific variants, certain testing may provide diagnostic benefits. M-HES variants are notable for increased serum B12 and FIP1L1-PDGFRA fusion genes. Anemia, thrombocytopenia, elevated serum tryptase, and hepatosplenomegaly have been noted. L-HES presents dermatologic symptoms, although other organs may be involved.

• #4 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  Human leukocyte antigen (HLA) typing should be done early in the course of hypereosinophilic syndrome for patients with aggressive disease, cytogenetic aberration, or the FIPL1/PDGFRA fusion gene. […] Initial evaluation of suspected hypereosinophilic syndrome should include tests to look for any evidence of end-organ damage. […] Wang has proposed an algorithm for the workup of patients with hypereosinophilia. […] Increased serum tryptase level suggests a FIP1L1-PDGFRA mutation; always rule out C-KIT mutation, which is characteristic of systemic mastocytosis whenever serum tryptase is elevated. […] Interleukin-5 (IL-5) levels are elevated in cases of hypereosinophilic syndrome that are associated with clonal T-cell disease. […] Immunoglobulin E (IgE) levels may be elevated, and hypergammaglobulinemia is common; increased IgE levels have prognostic significance.

• #4 Hypereosinophilic Syndrome: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/202030-overview

  Hypereosinophilic syndrome (HES) is a myeloproliferative disorder (MPD) characterized by persistent eosinophilia that is associated with damage to multiple organs. HES is classified into primary (clonal) HES, reactive HES, and (when the etiology is unclear) idiopathic HES. The World Health Organization (WHO) has updated its definition and classification of eosinophilic disorders and revised the diagnostic criteria for idiopathic HES. For a diagnosis of idiopathic HES, the absolute eosinophil count (AEC) must be sustained above 1500/L for longer than 6 months and tissue damage must be present. In addition, the following must be excluded: […] If all the other criteria are met but tissue damage is absent, the preferred diagnosis is idiopathic HE, rather than idiopathic HES. The differential diagnosis (see DDx) of HES includes other causes of eosinophilia, which may be classified as familial or acquired. Familial eosinophilia is an autosomal dominant disorder with a stable eosinophil count and a benign clinical course. Acquired eosinophilia is further divided into secondary, clonal, and idiopathic eosinophilia. Secondary eosinophilia is a cytokine-derived (interleukin-5 [IL-5]) reactive phenomenon. Clonal eosinophilia is diagnosed by bone marrow histology, cytogenetics, and molecular genetics. Idiopathic eosinophilia is a diagnosis of exclusion when secondary and clonal causes of eosinophilia have been ruled out. However, long-term follow-up and X-linked clonality studies indicate that at least some patients initially diagnosed with idiopathic HES have an underlying clonal myeloid malignancy or a clonal or phenotypically abnormal T-cell population, suggesting a true secondary process. The best-described aberration is the interstitial deletion on chromosome 4q12, resulting in fusion of the 5 portion of the FIP1L1 gene to the 3 portion of the PDGFRA gene. The prevalence of such a mutation is 0.4% in unselected cases of eosinophilia, but it can be as high as 1288% in cohorts with HES, particularly those with features of MPD (increased levels of tryptase and mast cells in the bone marrow). The other subset of idiopathic eosinophilia, HES with clonal or immunophenotypically aberrant T-cells, is associated with increased secretion of interleukin-5 and cutaneous manifestations. Chronic eosinophilic leukemia is caused by autonomous proliferation of clonal eosinophilic precursors. Simplified criteria for the diagnosis of chronic eosinophilic leukemia include the following: […] For discussion of cases in children, see Pediatric Hypereosinophilic Syndrome; for discussion of skin findings, see Dermatologic Manifestations of Hypereosinophilic Syndrome.

• #4 Managing Patients with Hypereosinophilic Syndrome: A Statement from the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC)

  https://www.mdpi.com/2073-4409/13/14/1180

  The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. […] In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches. […] The symptoms and disease severity can vary considerably among patients with eosinophilia. […] Interestingly, the clinical manifestation of HE can be identical regardless of its cause. […] In the first step of the diagnostic work-up, the presence of HE is confirmed. […] Then, the investigation focuses on determining the etiology of HE, particularly whether an underlying disease is contributing.

• #4

  https://www.omim.org/entry/607685

  The diagnosis of hypereosinophilic syndrome is based on the following criteria (Chusid et al., 1975): sustained eosinophilia (more than 1,500 eosinophils per cubic millimeter) for more than 6 months; the absence of other causes of eosinophilia, including parasitic infections and allergies; and signs and symptoms of organ involvement, most frequently the heart, the central and peripheral nervous system, lungs, and skin. […] The clonality of hypereosinophilic syndrome has been demonstrated in some cases by clonal karyotypic abnormalities and X-inactivation assays (Luppi et al., 1994; Chang et al., 1999). […] Klion et al. (2003) concluded that elevated serum tryptase is a sensitive marker of a myeloproliferative variant of HES that is characterized by tissue fibrosis, poor prognosis, and imatinib responsiveness.

• #4 Hypereosinophilic Syndrome and T-Cell Lymphoma: Which Comes First? | Actas Dermo-Sifiliográficas

  https://actasdermo.org/es-hypereosinophilic-syndrome-t-cell-lymphoma-articulo-S0001731023005902

  Eosinophilia has an important prognostic role in CTCL, with median survival 3 years lower in patients with eosinophil levels above 700/L. Some authors have considered eosinophilia on diagnosis as the only prognostic variable associated with disease progression and disease-related death. […] In summary, we can conclude that it is extremely difficult to know whether we are facing natural disease progression or an undiagnosed lymphoma, highlighting the need for more reliable markers to address this question. What we can say, based on the literature, is that eosinophilia is a warning sign for patients with CTCL, and long-term follow-up patients with L-HES are vital.

• #4 Pathology Outlines – Idiopathic hypereosinophilic syndrome

  https://www.pathologyoutlines.com/topic/myeloproliferativehypereosinophilicsyndrome.html

  Idiopathic hypereosinophilic syndrome is a disorder defined by peripheral blood eosinophilia (absolute eosinophil count ≥ 1.5 x 10^9/L) for at least 6 months with organ damage / dysfunction attributable to tissue hypereosinophilic infiltrate per biopsy and no discernible underlying etiology. […] Diagnosis of exclusion. […] Unexplained eosinophilia of ≥ 1.5 x 10^9/L for at least 6 months that leads to tissue damage. […] Exclude reactive causes of eosinophilia (parasites, drug related, allergy, etc.). […] Exclude acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes, myelodysplastic / myeloproliferative neoplasms and systemic mastocytosis. […] Tissue damage present due to hypereosinophilia. […] Bone marrow with increased eosinophilic precursors; proposed criteria of ≥ 20% marrow cellularity with or without peripheral blood eosinophilia. […] Affected organs may have increased eosinophils with eosinophil degranulation.

• #4 Hypereosinophilic syndrome: cardiac diagnosis and management | Heart

  https://heart.bmj.com/content/102/2/100.short

  Hypereosinophilic syndrome (HES) is a heterogeneous group of conditions that is defined at its core by hypereosinophilia (HE) (blood eosinophil count of 1.5109/L) and organ damage directly attributable to the HE. […] Once a significantly elevated eosinophil count is identified, it must be confirmed on repeat testing and the aetiology for the HE must be rigorously sought out with a focus on identifying whether organ dysfunction is occurring. […] Echocardiography is routinely performed to assess for cardiac involvement, looking for evidence of left ventricular and/or right ventricular apical obliteration or thrombi or a restrictive cardiomyopathy. […] Cardiac magnetic resonance imaging and CT are often useful adjuncts to establish the diagnosis but endomyocardial biopsy remains the gold standard. […] To decrease the degree of eosinophilia, treatment can include corticosteroids and/or imatinib based on the aetiology. Anticoagulation, standard heart failure therapy for a restrictive cardiomyopathy and finally cardiac transplantation may be indicated in the treatment algorithm.

• #4 Hypereosinophilic syndromes | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-37

  Classification of HES patients remains difficult in a routine setting, and requires referral of blood and/or marrow samples to qualified laboratories for optimal evaluation. […] At the present time, standard care demands that the three following tests be performed on peripheral blood and/or bone marrow for all patients: search for the F/P fusion gene using RT-PCR (reverse transcription polymerase chain reaction, preferably nested for increased sensitivity) and/or FISH (fluorescent in situ hybridisation) for the CHIC2 locus (absence of this locus is considered a surrogate marker for presence of the F/P fusion), lymphocyte phenotyping, and analysis of T cell receptor (TCR) gene rearrangement patterns. […] However, despite adherence to the preceding guidelines, a number of patients will remain unclassified. Additional investigations in a research setting that may help distinguish myeloid and lymphoid disorders include: analysis of cytokine profiles of T cell subsets including eosinophilopoietic (IL-3 and GM-CSF) and/or type 2 (IL-4, IL-5, IL-13) cytokines, measurement of serum tryptase and TARC levels, and cytogenetic analysis focusing on imatinib target tyrosine kinases.

• #4 Hypereosinophilic syndrome (Idiopathic hypereosinophilic syndrome) – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/hypereosinophilic-syndrome-idiopathic-hypereosinophilic-syndrome/

  The primary goal of treatment of HES is to decrease tissue eosinophilia and reduce eosinophil-associated damage to the tissue. Peripheral eosinophilia is a readily available laboratory value; however, it does not reliably predict the degree of tissue damage. In the absence of a reliable and validated biomarker, patients should be clinically followed closely. Serial echocardiograms are recommended every 6-12 months, particularly in M-HES, since cardiac involvement may be asymptomatic. Depending on clinical presentation, skin biopsy, pulmonary function test, scan imaging of chest or abdomen may be considered in follow up of patients. […] A crucial step in management of patients suspected to have HES is to exclude the secondary causes of eosinophilia that require specific treatment not directed towards eosinophilia. Parasitic infestations, most importantly strongyloidosis, should be excluded by an enzyme-linked immunsorbant assay in all patients with plausible history of exposure. Treating with corticosteroids can lead to fatal dissemination of this parasite.

• #4 HES – Exploring Best Practices for Diagnosis and Management of Hypereosinophilic Syndrome

  https://www.mycme.com/courses/hes-exploring-best-practices-for-diagnosis-and-management-of-hypereosinophilic-syndrome-7800

  Hypereosinophilic syndromes (HES) are a broad group of disorders that can lead to serious complications, including cardiovascular disease, cerebrovascular disease, and death. Due to their rarity, however, HESs are challenging to diagnose and treat. […] This activity is intended for allergists, immunologists, pulmonologists, along with other specialists and clinicians involved in the diagnosis and management of patients with hypereosinophilic syndrome. […] Upon completion of this activity, participants should be better able to: […] Perform differential diagnosis of eosinophilic disorders to identify patients with hypereosinophilic syndrome (HES).

• #4 The Diagnostic Work-Up of Hypereosinophilia – PubMed

  https://pubmed.ncbi.nlm.nih.gov/29961056/

  Hypereosinophilia (HE) is defined as a persistent elevated eosinophil count of 1.5 109/L. HE can be one of the dominant manifestations of a hematopoietic myeloid neoplasm or secondary/reactive to an underlying medical condition. If a cause of HE and its associated tissue/organ damage is not determined, the condition is considered to be idiopathic hypereosinophilic syndrome (HES). The work-up of HE can be challenging due to a broad range of causes of HE that can be either reactive or neoplastic. […] Using a multimodality approach and following a proper algorithm, a diagnosis can be made in a large proportion of patients. In idiopathic HES, myeloid neoplasm associated somatic mutations as evidence of clonality are reported in 20-25% patients; however, the mutation data should be interpreted cautiously considering the prevalence of clonal hematopoiesis of indeterminate potential (CHIP). Bone marrow morphology has been shown to have important value in the identification of a true myeloid neoplasm in these disorders. A genome-wide study may be needed to understand the „idiopathic” cases that would ultimately lead to better patient care.

• #5 Eosinophil Counts in Hypereosinophilic Syndrome (HES)

  https://eosinophilosophy.com/disease-state/hes/

  Hypereosinophilic syndrome (HES) is a rare group of disorders characterized by peripheral hypereosinophilia with eosinophil-mediated organ dysfunction and/or damage, with no other identifiable etiology for eosinophil-mediated organ damage. US estimated prevalence of HES is 5000 patients. […] Hypereosinophilia is a defining characteristic of HES. Hypereosinophilia is defined as: Blood EOS count of 1500 cells/L on 2 occasions with an interval of 1 month or longer and/or Histologically proven eosinophilia in tissue (defined by 1 or more of the following): Bone marrow aspiration with 20% eosinophils, Histologically proven tissue infiltration, Deposition of eosinophil-granule proteins. […] Sustained hypereosinophilia without an apparent cause should prompt a workup and consideration of HES.

• #5 Hypereosinophilic Syndrome

  https://www.aaaai.org/conditions-treatments/related-conditions/hypereosinophilic-syndrome

  When diagnosed with HES, it is important to determine the extent of organ damage. A chest x-ray and echocardiogram are routinely performed to evaluate the heart and lungs. Other tests often performed in HES patients include liver and kidney function, serum vitamin B12 levels, erythrocyte sedimentation rate (ESR) and serum tryptase levels.

• #5

  https://www.haematologica.org/article/view/5338

  Hypereosinophilic syndromes (HES) are a group of disorders characterized by persistent and marked hypereosinophilia (1500 per microliter) not due to an underlying disease known to cause eosinophil expansion (such as an allergic drug reaction or parasitic infection), and which is directly implicated in damage or dysfunction of at least one target organ or tissue. […] Efforts are now being directed towards improving diagnostic criteria and classification of disease forms, in order to better reflect these advances, and more importantly to provide physicians with a practical diagnostic approach to patients in whom chronic damage-inducing hypereosinophilia can not be resolved by treating an easily recognized underlying cause. […] However, this is challenging, as pathogenesis remains unknown in the majority of patients, and there are currently no valid biomarkers which reflect underlying mechanisms leading to hypereosinophilia.

• #5 Eosinophil Counts in Hypereosinophilic Syndrome (HES)

  https://eosinophilosophy.com/disease-state/hes/

  Differentiating between HES and eosinophilic granulomatosis with polyangiitis (EGPA) is challenging; both conditions have persistent eosinophilia and systemic manifestations. […] Differentiating between HES and single organ-restricted disease can be challenging. The magnitude of blood eosinophilia, with a combination of clinical and laboratory results, and pathologic and radiographic findings may be useful for differentiating HES from single-organ disease including (but not limited to): Eosinophilic esophagitis, Eosinophilic pneumonia, Severe eosinophilic asthma. […] Eosinophil counts can help guide treatment decisions. […] Per the World Health Organizations 2019 update on eosinophilic disorders, the goal of therapy in patients with hypereosinophilia is to mitigate eosinophil-mediated organ damage.

• #5

  https://www.haematologica.org/article/view/5338

  Early detection of FIP1L1-PDGFRA in patients with chronic unexplained hypereosiniphilia is now considered critical for optimal management, as its presence is associated with high spontaneous morbidity and mortality rates, and imatinib represents an extremely efficacious and generally well-tolerated first-line therapeutic agent for this condition. […] Thus, PCR for fusion gene detection and FISH for demonstration of CHIC2 deletion are becoming increasingly available in many specialized centers. […] Given the poor prognosis of FIP1L1-PDGFRA associated disease, treatment with imatinib is recommended even in the absence of clinical complications at the time the mutation is discovered; i.e. for the rare patients with still asymptomatic hypereosinophilia. […] There is some debate on the optimal dosing regimen, since doses as low as 100 mg once weekly have been shown to maintain clinical and molecular remission.

• #5 Hypereosinophilic Syndrome and T-Cell Lymphoma: Which Comes First? | Actas Dermo-Sifiliográficas

  https://actasdermo.org/es-hypereosinophilic-syndrome-t-cell-lymphoma-articulo-S0001731023005902

  Hypereosinophilic syndrome (HES) is defined by a concentration of eosinophils in peripheral blood greater than 1500cells/L, accompanied by organ damage or dysfunction not attributable to other causes. […] HESs include the lymphoproliferative form (L-HES), in which there is an abnormal T-cell (TC) population in peripheral blood, with clonal rearrangement of the TC receptors (TCRs). These produce eosinophil-derived cytokines. Therefore, unlike the clonal myeloproliferative variant, L-HES is a mixture of a clonal process (TC clones) and a reactive one (eosinophilia derived from the secretion of cytokines from these TCs). […] Close follow-up of these patients is essential, as 10-20% may progress to cutaneous T-cell lymphoma (CTCL) with a poor prognosis. It is important to distinguish between the 2 entities, given the indolent course in the case of patients with L-HES compared with the worse prognosis in CTCL.

• #5 Hypereosinophilic Syndrome (HES): Types, Symptoms, & More

  https://www.health.com/hypereosinophilic-syndrome-8546797

  Skin biopsy, which can be used to assess the cause of a rash. Your healthcare provider may take a small skin sample and send it to the lab, where a technician will examine it under a microscope to confirm the presence of eosinophils in the tissue. […] Bone marrow biopsy, which is done by removing a small amount of bone (usually from the hip bone) to look for abnormalities in white blood cells and measure the amount of eosinophils in the bone marrow. […] Allergy testing, such as skin prick or blood tests, can reveal allergies to specific substances (e.g., pollen) and diagnose allergic diseases.

• #5 Hypereosinophilic syndrome – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hypereosinophilic-syndrome/diagnosis-treatment/drc-20352856

  CT scan, to detect problems in the chest, abdomen and pelvis […] Echocardiogram or MRI, to assess heart function. […] Treatment for hypereosinophilic syndrome is aimed at reducing your eosinophil count to prevent tissue damage, especially to your heart. Specific treatment depends on your symptoms, the severity of your condition and the cause of your HES. […] For hypereosinophilic syndrome, some basic questions to ask the doctor include: […] Will I need additional tests? […] What are the treatment options? […] What are the benefits and risks of each treatment? […] Should I see additional specialists? What will that cost, and will my insurance cover it? […] Are there brochures or other printed material that I can have? What websites do you recommend? […] The doctor is likely to ask you several questions. Be ready to answer them to allow time later to cover other points you want to address. Examples include: […] Have you traveled out of the country lately? […] Do you have any allergies or skin conditions? […] Have you been exposed to any parasites such as hookworm?

• #5 How I Diagnose Hypereosinophilic Syndromes – European Medical Journal

  https://www.emjreviews.com/hematology/article/how-i-diagnose-hypereosinophilic-syndromes/

  T cell receptor (TCR) gene rearrangement studies have been increasingly used in the setting of eosinophilia to investigate T cell clonality and lymphocyte-variant HES. Clonal rearrangements are common, with one study finding 18 out of 42 (42.8%) patients to have TCR clonality. […] Myeloid/lymphoid neoplasms with eosinophilia and recurrent genetic rearrangements should be specifically excluded. The majority of these cases have a cryptic deletion of chromosome 4q12 creating the FIP1L1-PDGFRA fusion gene.

• #5 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  Human leukocyte antigen (HLA) typing should be done early in the course of hypereosinophilic syndrome for patients with aggressive disease, cytogenetic aberration, or the FIPL1/PDGFRA fusion gene. […] Initial evaluation of suspected hypereosinophilic syndrome should include tests to look for any evidence of end-organ damage. […] Wang has proposed an algorithm for the workup of patients with hypereosinophilia. […] Increased serum tryptase level suggests a FIP1L1-PDGFRA mutation; always rule out C-KIT mutation, which is characteristic of systemic mastocytosis whenever serum tryptase is elevated. […] Interleukin-5 (IL-5) levels are elevated in cases of hypereosinophilic syndrome that are associated with clonal T-cell disease. […] Immunoglobulin E (IgE) levels may be elevated, and hypergammaglobulinemia is common; increased IgE levels have prognostic significance.

• #5

  https://www.haematologica.org/article/view/5338

  Hence, doses below 100 mg daily are not recommended, and some authors even recommend higher dosing if treatment is well tolerated. […] In practical terms, the ideal dose of imatinib in a given patient is that required to induce and maintain molecular remission. […] Although eosinophil levels generally plummet within days in patients with PDGFRA rearrangements, disappearance of the molecular defect generally takes several months. […] It has now become common practice to perform T-cell phenotyping and to investigate TCR gene rearrangements on peripheral blood and, eventually, on bone marrow in patients with HES in order to identify those with L-HES. […] Given this, the conclusion can be drawn that formal diagnosis of L-HES currently requires careful T-cell phenotyping and PCR analysis of TCR gene rearrangements, ideally in conjunction with assessment of cytokine production by cultured PBMC or T cells.

• #5 Hypereosinophilic Syndrome: What It Is, Causes, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/22541-hypereosinophilic-syndrome

  Healthcare providers use a process of elimination to diagnose HES. […] If you’re still having symptoms, your healthcare provider might test your blood for high eosinophil levels. […] They might also perform a biopsy to confirm a hypereosinophilic syndrome diagnosis. […] Healthcare providers focus on reducing the high eosinophil levels in your blood and tissues. […] Standard treatment includes corticosteroids and chemotherapy drugs. […] Generally speaking, the sooner your HES is diagnosed and treated, the less likely you are to have lasting problems. […] Hypereosinophilic syndrome (HES) is a rare medical condition that can be difficult to diagnose. […] The good news is, once your HES is diagnosed, there are successful treatments for it.

• #6 Hypereosinophilic Syndromes (HES) Diagnosis

  https://www.nationaljewish.org/conditions/hypereosinophilic-syndromes/diagnosis

  Test results will be reviewed by the doctor to decide if the condition is in fact HES. […] These criteria are: […] Eosinophil count in the blood greater than or equal to 1500/microliter, and lasting for more than 6 months […] Signs and/or symptoms of organs not working properly due to white blood cells attacking the organs, and […] No other apparent explanations for the increased white blood cells, such as parasitic infection or allergic disease. If vital organs like the heart or bone marrow are not working properly and its happening quickly, a doctor will not wait 6 months before diagnosing and considering prompt treatment for the HES.

• #6 Hyper eosinophilic diseases – diagnosis and therapeuti…

  https://otolaryngologypl.com/seo/article/01.3001.0054.8684/en

  Hypereosinophilia may be the dominant manifestation of hematological diseases such as hematopoietic myeloid neoplasm or lymphoma. […] Each case of hypereosinophilia needs to be evaluated quickly and carefully. […] We divided our diagnostic recommendations into two parts. […] If the cause of hypereosinophilia remains unknown, the patient should be referred to the tertiary referral center specializing in internal medicine, pulmonology, or allergology. […] In patients with I-HES the recommended dose is 300 mg every 4 weeks. […] The diagnosis of I-HES is based on differential diagnostics against secondary causes of hypereosinophilia and requires confirmation of chronic hypereosinophilia (EOS >1.5 G/L) with the results of two consecutive tests generally performed at least 4 weeks apart.

• #6 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  Eosinophilia is present ( 1500 cells/L). […] Echocardiography is helpful in the initial evaluation and monitoring of cardiac disease in patients suspected with hypereosinophilic syndrome. […] An endocardial biopsy may be performed via cardiac catheterization if any question about the diagnosis of hypereosinophilic syndrome exists. […] Perform bone marrow aspiration and biopsy, and submit samples for cytogenetic studies. […] Eosinophil infiltrates are present in affected tissues in patients with hypereosinophilic syndrome.

• #6 Hypereosinophilic syndrome – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hypereosinophilic-syndrome/diagnosis-treatment/drc-20352856

  Many types of disorders can raise your eosinophil level, including certain infections, allergies and reactions to medications. When trying to determine whether you have hypereosinophilic syndrome (HES), your doctor is likely to ask about your travel history and any medications you’re taking, to help rule out these other causes. […] Your doctor may also need information from some of the following lab tests: […] Blood tests, to detect autoimmune conditions, parasitic infections, or problems with your liver or kidneys […] Allergy tests, to detect environmental or food allergies […] Stool tests, to detect parasitic infections such as hookworm […] Genetic test, to check for a gene mutation that can cause HES. […] Imaging tests may include: […] X-rays, to check the condition of your lungs

• #6 Hypereosinophilic syndromes | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-37

  Classification of HES patients remains difficult in a routine setting, and requires referral of blood and/or marrow samples to qualified laboratories for optimal evaluation. […] At the present time, standard care demands that the three following tests be performed on peripheral blood and/or bone marrow for all patients: search for the F/P fusion gene using RT-PCR (reverse transcription polymerase chain reaction, preferably nested for increased sensitivity) and/or FISH (fluorescent in situ hybridisation) for the CHIC2 locus (absence of this locus is considered a surrogate marker for presence of the F/P fusion), lymphocyte phenotyping, and analysis of T cell receptor (TCR) gene rearrangement patterns. […] However, despite adherence to the preceding guidelines, a number of patients will remain unclassified. Additional investigations in a research setting that may help distinguish myeloid and lymphoid disorders include: analysis of cytokine profiles of T cell subsets including eosinophilopoietic (IL-3 and GM-CSF) and/or type 2 (IL-4, IL-5, IL-13) cytokines, measurement of serum tryptase and TARC levels, and cytogenetic analysis focusing on imatinib target tyrosine kinases.

• #6 Hypereosinophilic syndrome (Idiopathic hypereosinophilic syndrome) – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/hypereosinophilic-syndrome-idiopathic-hypereosinophilic-syndrome/

  The primary goal of treatment of HES is to decrease tissue eosinophilia and reduce eosinophil-associated damage to the tissue. Peripheral eosinophilia is a readily available laboratory value; however, it does not reliably predict the degree of tissue damage. In the absence of a reliable and validated biomarker, patients should be clinically followed closely. Serial echocardiograms are recommended every 6-12 months, particularly in M-HES, since cardiac involvement may be asymptomatic. Depending on clinical presentation, skin biopsy, pulmonary function test, scan imaging of chest or abdomen may be considered in follow up of patients. […] A crucial step in management of patients suspected to have HES is to exclude the secondary causes of eosinophilia that require specific treatment not directed towards eosinophilia. Parasitic infestations, most importantly strongyloidosis, should be excluded by an enzyme-linked immunsorbant assay in all patients with plausible history of exposure. Treating with corticosteroids can lead to fatal dissemination of this parasite.

• #6 Identifying HES | NUCALA (mepolizumab) for HCPs

  https://nucalahcp.com/hes/identifying-hes/

  Each patient with hypereosinophilic syndrome (HES) may present differently, and since HES is a rare disease (estimated prevalence of 5000 in the US*), it may be more difficult to diagnose. A thorough workup is essential for evaluating a patient who is presenting with hypereosinophilia. […] HES is also a rare disease defined by hypereosinophilia, with a blood eosinophil count greater than 1500 cells per microliter, no known secondary cause of the hypereosinophilia, and eosinophil-mediated organ dysfunction. It is important that sustained blood eosinophilia without an apparent cause prompt a workup and consideration of hypereosinophilic syndromes. […] HES has multiple components to its definition. When diagnosing HES, note that the criteria for peripheral blood hypereosinophilia must be fulfilled first. Two additional criteria must be met to make the HES diagnosis. There must be evidence of eosinophil-mediated organ dysfunction and/or damage. Also, any other identifiable causes for eosinophilic organ damage must be ruled out. […] In the case of evolving, life-threatening, end-organ damage, the diagnosis of HES can be made immediately to avoid delay in therapy.

• #7 Eosinophilic disorders: evaluation of current classification and diagnostic criteria, proposal of a practical diagnostic algorithm | Clinical and Translational Allergy | Full Text

  https://ctajournal.biomedcentral.com/articles/10.1186/s13601-019-0277-4

  The 2010 revision of HES diagnosis criteria recommended that a peripheral AEC1500/mm3 not be a requirement for HES diagnosis, as previously considered, due to possible discrepancies between blood and tissue eosinophilia. […] The initial concept of hypereosinophilic syndrome (HES) was introduced by Hardy and Anderson in 1968, corresponding to a severe clinical entity defined by persistent blood eosinophilia without clear cause, multiorgan involvement and fatal outcome. […] The first diagnostic criteria of primary or idiopathic HES were stated in 1975 by Chusid, including the following: persistent blood absolute eosinophil count over 1500/mm3 for a duration of more than 6 months, with evidence of tissue and organ damage, without any identifiable cause of eosinophilia. […] The identification of the mechanism and molecular characterization of HES subtype is essential for predicting clinical outcome, treatment selection and prognosis.

• #7 Idiopathic hypereosinophilic syndrome | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/idiopathic-hypereosinophilic-syndrome?lang=us

  Idiopathic hypereosinophilic syndrome (IHES) is a leukoproliferative disorder and refers to a situation when there is an unexplained prolonged eosinophilia with associated organ system dysfunction. […] Individuals have prolonged raised total leukocyte counts with raised eosinophil counts. Usually the total leukocyte counts are less than 25,000/L with 30-70% comprising of eosinophils. At times extremely high leukocyte counts (90,000/L) can also develop which can then result in a poorer prognosis. […] The condition can affect several organ systems which includes: […] Radiographic features are probably best discussed under individual categories. […] Ultrasound may show hypoechoic lesions if there is liver involvement.

• #7 Hypereosinophilic Syndrome Workup: Approach Considerations, Blood Studies, Imaging Studies

  https://emedicine.medscape.com/article/202030-workup

  Bone marrow biopsy should be evaluated for the following: Morphologic examinations to look for features of myeloproliferative disorders (MPDs) and to look for dense aggregates of mast cells, Special stains should include reticulin stain for myelofibrosis and tryptase staining for mast cells when serum tryptase levels are elevated, Cytogenetics: Most patients with hypereosinophilic syndrome have normal karyotypes; in those who have cytogenetic changes, the changes may vary from aneuploidy to Philadelphia chromosome, Molecular genetic studies: FIP1L1/PDGFRA should be evaluated in all patients with increased tryptase levels; this mutation is present in both hypereosinophilic syndrome and systemic mastocytosis; C-KIT mutation should also be evaluated in patients with increased tryptase levels.

• #7 Hypereosinophilic syndromes | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-37

  Classification of HES patients remains difficult in a routine setting, and requires referral of blood and/or marrow samples to qualified laboratories for optimal evaluation. […] At the present time, standard care demands that the three following tests be performed on peripheral blood and/or bone marrow for all patients: search for the F/P fusion gene using RT-PCR (reverse transcription polymerase chain reaction, preferably nested for increased sensitivity) and/or FISH (fluorescent in situ hybridisation) for the CHIC2 locus (absence of this locus is considered a surrogate marker for presence of the F/P fusion), lymphocyte phenotyping, and analysis of T cell receptor (TCR) gene rearrangement patterns. […] However, despite adherence to the preceding guidelines, a number of patients will remain unclassified. Additional investigations in a research setting that may help distinguish myeloid and lymphoid disorders include: analysis of cytokine profiles of T cell subsets including eosinophilopoietic (IL-3 and GM-CSF) and/or type 2 (IL-4, IL-5, IL-13) cytokines, measurement of serum tryptase and TARC levels, and cytogenetic analysis focusing on imatinib target tyrosine kinases.

• #7 Hypereosinophilic syndrome (Idiopathic hypereosinophilic syndrome) – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/hypereosinophilic-syndrome-idiopathic-hypereosinophilic-syndrome/

  The primary goal of treatment of HES is to decrease tissue eosinophilia and reduce eosinophil-associated damage to the tissue. Peripheral eosinophilia is a readily available laboratory value; however, it does not reliably predict the degree of tissue damage. In the absence of a reliable and validated biomarker, patients should be clinically followed closely. Serial echocardiograms are recommended every 6-12 months, particularly in M-HES, since cardiac involvement may be asymptomatic. Depending on clinical presentation, skin biopsy, pulmonary function test, scan imaging of chest or abdomen may be considered in follow up of patients. […] A crucial step in management of patients suspected to have HES is to exclude the secondary causes of eosinophilia that require specific treatment not directed towards eosinophilia. Parasitic infestations, most importantly strongyloidosis, should be excluded by an enzyme-linked immunsorbant assay in all patients with plausible history of exposure. Treating with corticosteroids can lead to fatal dissemination of this parasite.

• #8 Managing Patients with Hypereosinophilic Syndrome: A Statement from the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC)

  https://www.mdpi.com/2073-4409/13/14/1180

  Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. […] Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. […] On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. […] The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES—Italian Network on HES) for patients and physicians.

• #9 Hypereosinophilic syndrome – Overview of Information and Clinical Research

  https://clinicaltrials.eu/disease/hypereosinophilic-syndrome/

  Hypereosinophilic syndrome (HES) is a rare disorder characterized by an elevated eosinophil count in the blood, typically 1.5 x 10^9/L or higher, and associated with organ damage due to eosinophilia. The condition requires careful management to prevent serious complications, and treatment strategies are tailored based on the clinical presentation and underlying genetic mutations. […] The primary goal in treating HES is to reduce the high eosinophil levels in the blood and tissues. Corticosteroids are the first-line therapy for most forms of HES, especially in cases without the FIP1L1/PDGFRA mutation. […] Patients with HES require regular monitoring to ensure that eosinophilia is controlled and to detect any new or worsening organ involvement. Asymptomatic patients are typically monitored with serum troponin measurements and echocardiography at regular intervals. Consulting a hematologist is advised for the diagnosis, management, and follow-up care of patients with unexplained eosinophilia. […] HES is diagnosed through blood tests showing elevated eosinophil counts, along with assessments for organ damage and genetic testing for specific mutations.

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