Materiały źródłowe

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

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

  Hypereosinophilic syndrome is a rare medical condition caused by an overload of white blood cells called eosinophils. […] Hypereosinophilic syndrome happens when eosinophilia accelerates, speeding up eosinophil production and increasing the number of eosinophils. […] Researchers dont know all the factors that trigger the dramatic increase in eosinophils that causes most of the cases of hypereosinophilic syndrome. They have, though, identified a few conditions or circumstances that might be responsible: […] A genetic abnormality that drives cell growth. […] Unfortunately, researchers dont know what causes most HES cases or what you can do to prevent it.

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

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

  Eosinophils belong to the myeloid lineage, and differentiate from myeloid progenitors (GEMM-CFU) in bone marrow. Among the three cytokines that act as eosinophil growth factors and apoptosis inhibitors, i.e. granulocyte-macrophage colony stimulating factor (GM-CSF), IL-3, and IL-5, only the latter displays specificity for eosinophils. The major source of this eosinophil-specific cytokine is represented by so-called „type 2” helper T cells. Recent studies based on material from patients fulfilling Chusid’s HES diagnostic criteria have shown that two distinct underlying mechanisms may lead to chronic unexplained hypereosinophilia in HES patient subgroups: occurrence of a sporadic hematopoetic stem cell mutation, leading to primitive clonal expansion of cells belonging to the myeloid lineage with preferential eosinophilic differentiation (as such, hypereosinophilia belongs to the group of chronic myeloproliferative disorders), or overproduction of eosinophilopoietic cytokine(s) by an activated population of T cells (in the „lymphocytic variant” of HES, or L-HES).

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

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

  Hypereosinophilic syndrome is a rare medical condition caused by an overload of white blood cells called eosinophils. […] Hypereosinophilic syndrome happens when eosinophilia accelerates, speeding up eosinophil production and increasing the number of eosinophils. […] Researchers dont know all the factors that trigger the dramatic increase in eosinophils that causes most of the cases of hypereosinophilic syndrome. They have, though, identified a few conditions or circumstances that might be responsible: […] A genetic abnormality that drives cell growth. […] Unfortunately, researchers dont know what causes most HES cases or what you can do to prevent it.

• #4 Hypereosinophilic Syndrome – StatPearls – NCBI Bookshelf

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

  Based on the initial patient evaluation, HES can be classified into 5 clinically relevant variants: […] Primary/Neoplastic (HESN) […] Myeloid variants (M-HES): Classified into various subtypes, including platelet-derived growth factor receptor alpha FIP1L1-PDGFRA fusion gene (F/P pos variant), which occurs secondary to an interstitial chromosomal deletion on 4q12. […] T-cell lymphocytic variants (L-HES): Caused by aberrant IL-5-producing T-cells, such as CD3-CD4+ T cell-associated disease. […] Secondary/Reactive (HESR) […] Specific/defined hypereosinophilic syndromes secondary to an underlying condition such as an infectious or inflammatory process. […] Familial HES (HESFA) […] Namely when there is a family history of documented persistent hypereosinophilia of unknown cause. […] Idiopathic (IHES) […] Hypereosinophilia with no clear underlying cause associated with end-organ damage. […] Organ-Restricted HES […] Namely, when tissue hypereosinophilia is present, it causes end-organ damage, but HES blood criteria are unmet.

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

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

  Based on the initial patient evaluation, HES can be classified into 5 clinically relevant variants: […] Primary/Neoplastic (HESN): Myeloid variants (M-HES): Classified into various subtypes, including platelet-derived growth factor receptor alpha FIP1L1-PDGFRA fusion gene (F/P pos variant), which occurs secondary to an interstitial chromosomal deletion on 4q12. […] T-cell lymphocytic variants (L-HES): Caused by aberrant IL-5-producing T-cells, such as CD3-CD4+ T cell-associated disease. […] Secondary/Reactive (HESR): Specific/defined hypereosinophilic syndromes secondary to an underlying condition such as an infectious or inflammatory process. Examples include: helminth infections, episodic angioedema, and eosinophilic granulomatosis with polyangiitis (EGPA). […] Familial HES (HESFA): Namely when there is a family history of documented persistent hypereosinophilia of unknown cause. […] Idiopathic (IHES): Hypereosinophilia with no clear underlying cause associated with end-organ damage. […] Organ-Restricted HES: Namely, when tissue hypereosinophilia is present, it causes end-organ damage, but HES blood criteria are unmet.

• #6 Hypereosinophilic Syndrome (HES) – Patient Worthy

  https://patientworthy.com/hypereosinophilic-syndrome/

  Hypereosinophilic syndrome (HES) is a rare blood disorder characterized by a high level of eosinophils, which are white blood cells necessary for immune system function. The exact cause of HES is unknown. HES is diagnosed when all other reasons for the elevated eosinophils are ruled out. Research is being done to determine the exact cause. An emerging theory is that there is an inherited genetic cause. […] The elevated eosinophils must be present for 6 months or longer and have no known cause to be classified as HES.

• #7 Practical approach to the patient with hypereosinophilia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2902584/

  These criteria no longer reflect clinical practice which integrates modern diagnostic and management facilities and recent advances in pathogenic mechanisms. […] Recent studies have led to the identification of two major pathogenically identifiable variants of HES. Myeloproliferative variant HES (M-HES) is characterized by features that are typically encountered in other myeloproliferative diseases, including increased serum vitamin B12, hepatomegaly, splenomegaly, anemia, thrombocytopenia, circulating myeloid precursors, and increased BM cellularity with a left-shift in maturation. […] The lymphocytic HES (L-HES) variant is characterized by polyclonal eosinophil expansion in response to marked over-production of IL-5 by deregulated T-cells in vivo. […] In the majority of cases of HES, not due to M-HES or L-HES variants, depending on the nature and severity of clinical complications of hypereosinophilia, treatment of idiopathic HES may or may not be necessary, depending on evidence of associated organ involvement.

• #8 Practical approach to the patient with hypereosinophilia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2902584/

  These criteria no longer reflect clinical practice which integrates modern diagnostic and management facilities and recent advances in pathogenic mechanisms. […] Recent studies have led to the identification of two major pathogenically identifiable variants of HES. Myeloproliferative variant HES (M-HES) is characterized by features that are typically encountered in other myeloproliferative diseases, including increased serum vitamin B12, hepatomegaly, splenomegaly, anemia, thrombocytopenia, circulating myeloid precursors, and increased BM cellularity with a left-shift in maturation. […] The lymphocytic HES (L-HES) variant is characterized by polyclonal eosinophil expansion in response to marked over-production of IL-5 by deregulated T-cells in vivo. […] In the majority of cases of HES, not due to M-HES or L-HES variants, depending on the nature and severity of clinical complications of hypereosinophilia, treatment of idiopathic HES may or may not be necessary, depending on evidence of associated organ involvement.

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

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

  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. […] Patients with HES with the PDGFRA mutation have a very high incidence of cardiac involvement and carry a poor prognosis without therapy. […] 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. […] Some of the cytogenetic abnormalities that have been described in chronic eosinophilic leukemia include t(5:12) and t(8:13), and molecular genetic abnormalities include the FIP1L1-PDGFRA fusion gene and ETV6-PDGFR.

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

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

  Recently, a cryptic cytogenetic abnormality (which is invisible on routine karyotypes) has been identified in eosinophils from a significant proportion of HES patients, establishing the existence of a clonal myeloproliferative disorder. Briefly, an interstitial deletion on chromosome 4q12 results in fusion of two genes, FIP1L1 and PDGFRA. The new fusion gene encodes a FIP1LI-PDGFRA (F/P) protein displaying constitutive tyrosine kinase activity, whose role in disease induction has been confirmed by its disappearance in patients successfully treated with the tyrosine kinase inhibitor, imatinib. […] In L-HES, overproduction of eosinophil growth factors by T cells leads to increased cycling, differentiation and maturation of eosinophil precursors, as well as prolonged survival of eosinophils in the periphery, resulting in non-clonal hypereosinophilia. Interleukin-5-producing T cell subsets have been described in blood of approximately 35 patients with HES, and a rough estimate would be that at most one fourth of HES patients present this variant.

• #11

  https://omim.org/entry/607685

  A number sign (#) is used with this entry because some cases of hypereosinophilic syndrome are caused by fusion between the FIP1-like-1 (FIP1L1; 607686) and platelet-derived growth factor receptor-alpha (PDGFRA; 173490) genes. […] Idiopathic hypereosinophilic syndrome (HES) is a myeloproliferative disorder in which persistent eosinophilia leads to tissue damage, caused by direct infiltration by eosinophils and cytokine release, which leads to progressive organ dysfunction that may be fatal (summary by Griffin et al., 2003). […] Cools et al. (2003) found that a hypereosinophilic syndrome patient being treated with imatinib had a complex chromosomal abnormality; this led to the identification of fusion of the FIP1L1 gene to the PDGFRA gene, which was caused by an interstitial deletion on chromosome 4q12. The resulting FIP1L1-PDGFRA gene was found to be a constitutively activated tyrosine kinase that transforms hematopoietic cells and is inhibited by imatinib. […] Griffin et al. (2003) found the 4q12 deletion in patients with HES, resulting in the same fusion gene involving PDGFRA and FIP1L1. They suggested that FIP1L1 be referred to as RAG (rearranged in hypereosinophilia).

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

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

  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. […] Patients with HES with the PDGFRA mutation have a very high incidence of cardiac involvement and carry a poor prognosis without therapy. […] 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. […] Some of the cytogenetic abnormalities that have been described in chronic eosinophilic leukemia include t(5:12) and t(8:13), and molecular genetic abnormalities include the FIP1L1-PDGFRA fusion gene and ETV6-PDGFR.

• #13 Hypereosinophilic Syndrome – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/eosinophilic-disorders/hypereosinophilic-syndrome

  Patients with the myeloproliferative subtype often develop endomyocardial fibrosis and may rarely develop acute myeloid leukemia or acute lymphoblastic leukemia. […] A small proportion of patients with the myeloproliferative variant of hypereosinophilic syndrome have cytogenetic changes involving platelet-derived growth factor receptor beta (PDGFRB) and may also be responsive to tyrosine kinase inhibitors such as imatinib. […] Other cytogenetic abnormalities include rearrangement of the gene for fibroblast growth factor receptor 1 (FGFR1) or Janus kinase 2 (PCM1-JAK2). […] Recently, ETV6-ABL1 and various FLT3 fusions have been added to the gene rearrangements associated with hypereosinophilia. […] The lymphoproliferative variant is associated with a clonal population of T cells with aberrant phenotype.

• #14 Hypereosinophilic Syndrome – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/eosinophilic-disorders/hypereosinophilic-syndrome

  Patients with the myeloproliferative subtype often develop endomyocardial fibrosis and may rarely develop acute myeloid leukemia or acute lymphoblastic leukemia. […] A small proportion of patients with the myeloproliferative variant of hypereosinophilic syndrome have cytogenetic changes involving platelet-derived growth factor receptor beta (PDGFRB) and may also be responsive to tyrosine kinase inhibitors such as imatinib. […] Other cytogenetic abnormalities include rearrangement of the gene for fibroblast growth factor receptor 1 (FGFR1) or Janus kinase 2 (PCM1-JAK2). […] Recently, ETV6-ABL1 and various FLT3 fusions have been added to the gene rearrangements associated with hypereosinophilia. […] The lymphoproliferative variant is associated with a clonal population of T cells with aberrant phenotype.

• #15 Hypereosinophilic Syndrome – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/eosinophilic-disorders/hypereosinophilic-syndrome

  Patients with the myeloproliferative subtype often develop endomyocardial fibrosis and may rarely develop acute myeloid leukemia or acute lymphoblastic leukemia. […] A small proportion of patients with the myeloproliferative variant of hypereosinophilic syndrome have cytogenetic changes involving platelet-derived growth factor receptor beta (PDGFRB) and may also be responsive to tyrosine kinase inhibitors such as imatinib. […] Other cytogenetic abnormalities include rearrangement of the gene for fibroblast growth factor receptor 1 (FGFR1) or Janus kinase 2 (PCM1-JAK2). […] Recently, ETV6-ABL1 and various FLT3 fusions have been added to the gene rearrangements associated with hypereosinophilia. […] The lymphoproliferative variant is associated with a clonal population of T cells with aberrant phenotype.

• #16 Practical approach to the patient with hypereosinophilia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2902584/

  These criteria no longer reflect clinical practice which integrates modern diagnostic and management facilities and recent advances in pathogenic mechanisms. […] Recent studies have led to the identification of two major pathogenically identifiable variants of HES. Myeloproliferative variant HES (M-HES) is characterized by features that are typically encountered in other myeloproliferative diseases, including increased serum vitamin B12, hepatomegaly, splenomegaly, anemia, thrombocytopenia, circulating myeloid precursors, and increased BM cellularity with a left-shift in maturation. […] The lymphocytic HES (L-HES) variant is characterized by polyclonal eosinophil expansion in response to marked over-production of IL-5 by deregulated T-cells in vivo. […] In the majority of cases of HES, not due to M-HES or L-HES variants, depending on the nature and severity of clinical complications of hypereosinophilia, treatment of idiopathic HES may or may not be necessary, depending on evidence of associated organ involvement.

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

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

  Recently, a cryptic cytogenetic abnormality (which is invisible on routine karyotypes) has been identified in eosinophils from a significant proportion of HES patients, establishing the existence of a clonal myeloproliferative disorder. Briefly, an interstitial deletion on chromosome 4q12 results in fusion of two genes, FIP1L1 and PDGFRA. The new fusion gene encodes a FIP1LI-PDGFRA (F/P) protein displaying constitutive tyrosine kinase activity, whose role in disease induction has been confirmed by its disappearance in patients successfully treated with the tyrosine kinase inhibitor, imatinib. […] In L-HES, overproduction of eosinophil growth factors by T cells leads to increased cycling, differentiation and maturation of eosinophil precursors, as well as prolonged survival of eosinophils in the periphery, resulting in non-clonal hypereosinophilia. Interleukin-5-producing T cell subsets have been described in blood of approximately 35 patients with HES, and a rough estimate would be that at most one fourth of HES patients present this variant.

• #18 Hypereosinophilic Syndrome – StatPearls – NCBI Bookshelf

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

  Based on the initial patient evaluation, HES can be classified into 5 clinically relevant variants: […] Primary/Neoplastic (HESN) […] Myeloid variants (M-HES): Classified into various subtypes, including platelet-derived growth factor receptor alpha FIP1L1-PDGFRA fusion gene (F/P pos variant), which occurs secondary to an interstitial chromosomal deletion on 4q12. […] T-cell lymphocytic variants (L-HES): Caused by aberrant IL-5-producing T-cells, such as CD3-CD4+ T cell-associated disease. […] Secondary/Reactive (HESR) […] Specific/defined hypereosinophilic syndromes secondary to an underlying condition such as an infectious or inflammatory process. […] Familial HES (HESFA) […] Namely when there is a family history of documented persistent hypereosinophilia of unknown cause. […] Idiopathic (IHES) […] Hypereosinophilia with no clear underlying cause associated with end-organ damage. […] Organ-Restricted HES […] Namely, when tissue hypereosinophilia is present, it causes end-organ damage, but HES blood criteria are unmet.

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

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

  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. […] Patients with HES with the PDGFRA mutation have a very high incidence of cardiac involvement and carry a poor prognosis without therapy. […] 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. […] Some of the cytogenetic abnormalities that have been described in chronic eosinophilic leukemia include t(5:12) and t(8:13), and molecular genetic abnormalities include the FIP1L1-PDGFRA fusion gene and ETV6-PDGFR.

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

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

  Recently, a cryptic cytogenetic abnormality (which is invisible on routine karyotypes) has been identified in eosinophils from a significant proportion of HES patients, establishing the existence of a clonal myeloproliferative disorder. Briefly, an interstitial deletion on chromosome 4q12 results in fusion of two genes, FIP1L1 and PDGFRA. The new fusion gene encodes a FIP1LI-PDGFRA (F/P) protein displaying constitutive tyrosine kinase activity, whose role in disease induction has been confirmed by its disappearance in patients successfully treated with the tyrosine kinase inhibitor, imatinib. […] In L-HES, overproduction of eosinophil growth factors by T cells leads to increased cycling, differentiation and maturation of eosinophil precursors, as well as prolonged survival of eosinophils in the periphery, resulting in non-clonal hypereosinophilia. Interleukin-5-producing T cell subsets have been described in blood of approximately 35 patients with HES, and a rough estimate would be that at most one fourth of HES patients present this variant.

• #21 Hypereosinophilic Syndrome – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/eosinophilic-disorders/hypereosinophilic-syndrome

  Patients with the lymphoproliferative variant also more often respond favorably to corticosteroids and occasionally develop T-cell lymphoma. […] Other hypereosinophilic syndrome variants include Gleich syndrome (episodic angioedema with eosinophilia), familial hypereosinophilic syndrome mapped to 5q 31-33, and other organ-specific syndromes. […] Death usually results from organ, particularly cardiac, dysfunction. […] Prognosis varies depending on response to therapy. […] Response to imatinib improves the prognosis among patients with the FIP1L1/PDGFRA-associated fusion gene and other responsive gene fusions.

• #22 Hypereosinophilic syndrome – Two cases with varied manifestations – Journal of Skin and Sexually Transmitted Diseases

  https://jsstd.org/hypereosinophilic-syndrome-two-cases-with-varied-manifestations/

  HES is classified into myeloproliferative, lymphocytic, undefined, familial, overlap, and associated types. […] Myeloproliferative HES is often seen in males, may or may not be associated with positive FIP1L1-PDGFRA mutation and commonly accompanied by cardiac involvement. […] In contrast to myeloid HES, lymphocytic HES shows no sex predilection. […] Mucocutaneous manifestations described in HES are pruritus, angioedema, urticaria, purpuric macules, papules, plaques, nodules, mucosal ulcers, gangrene, livedo reticularis, Raynauds phenomenon, vesicles, eczematous lesions, and vasculitis. […] HES should be a differential diagnosis in all cases of persistent eosinophilia. A full workup is mandatory before making a diagnosis of HES. Failure to detect the condition early may lead to irreversible cardiac damage.

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

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

  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. […] Patients with HES with the PDGFRA mutation have a very high incidence of cardiac involvement and carry a poor prognosis without therapy. […] 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. […] Some of the cytogenetic abnormalities that have been described in chronic eosinophilic leukemia include t(5:12) and t(8:13), and molecular genetic abnormalities include the FIP1L1-PDGFRA fusion gene and ETV6-PDGFR.

• #24 Hypereosinophilic Syndrome – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/eosinophilic-disorders/hypereosinophilic-syndrome

  Patients with the lymphoproliferative variant also more often respond favorably to corticosteroids and occasionally develop T-cell lymphoma. […] Other hypereosinophilic syndrome variants include Gleich syndrome (episodic angioedema with eosinophilia), familial hypereosinophilic syndrome mapped to 5q 31-33, and other organ-specific syndromes. […] Death usually results from organ, particularly cardiac, dysfunction. […] Prognosis varies depending on response to therapy. […] Response to imatinib improves the prognosis among patients with the FIP1L1/PDGFRA-associated fusion gene and other responsive gene fusions.

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

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

  Hypereosinophilic syndrome (HES) is classified into primary (clonal) HES, reactive HES, and (when the etiology is unclear) idiopathic HES. […] The differential diagnosis (see DDx) of HES includes other causes of eosinophilia, which may be classified as familial or acquired. […] 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. […] The literature now favors the view that cases of idiopathic HES with FIP1L1 indeed represent chronic eosinophilic leukemia, because these patients have a molecular genetic abnormality, specifically an FIP1L1PDGFRA fusion gene.

• #26 Practical approach to the patient with hypereosinophilia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2902584/

  An initial consideration of etiologies for eosinophilia needs to focus on several not uncommon causes. Helminthic parasites typically elicit IL-5-mediated eosinophil expansion. […] While it is assumed that eosinophilia associated with adverse drug reactions is IL-5 mediated, in many instances the mechanism and the organ-targeted involvements elicited by medications remain unclear. […] Besides these relatively common causes of eosinophilia, neoplastic diseases, including varied adenocarcinomas, some forms of Hodgkin’s disease, T cell lymphoma, and mastocytosis, may be associated with paraneoplastic eosinophilia, as noted above. […] When an underlying etiology for persistent hypereosinophilia is not identified despite thorough diagnostic evaluation, clinicians must consider the diagnosis of hypereosinophilic syndromes (HES), which comprise a heterogeneous group of uncommon disorders.

• #27 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-Causes-Eosinophilia.aspx

  Eosinophilia is classified as primary or secondary, in addition to the hypereosinophilic syndromes. […] Hypereosinophilic syndromes are disorders which are characterized by eosinophilia above 1500/L persisting for at least 6 months, with no underlying disease condition, but associated with organ dysfunction due to eosinophil recruitment into tissues which suffer resulting damage. […] The following simple classification may help to understand the manifold conditions which may give rise to secondary eosinophilia. […] Certain tumors, such as Hodgkins disease, also result in eosinophilia. […] Invasive parasite infestations result in a rise in the number of peripheral blood eosinophils, such as Ascariasis (tapeworm infestation), Echinococcosis (dog tapeworm infestation), Filariasis, Cysticercosis, Hookworm, Visceral larva migrans, Schistosomiasis (liver fluke infection).

• #28 Practical approach to the patient with hypereosinophilia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2902584/

  An initial consideration of etiologies for eosinophilia needs to focus on several not uncommon causes. Helminthic parasites typically elicit IL-5-mediated eosinophil expansion. […] While it is assumed that eosinophilia associated with adverse drug reactions is IL-5 mediated, in many instances the mechanism and the organ-targeted involvements elicited by medications remain unclear. […] Besides these relatively common causes of eosinophilia, neoplastic diseases, including varied adenocarcinomas, some forms of Hodgkin’s disease, T cell lymphoma, and mastocytosis, may be associated with paraneoplastic eosinophilia, as noted above. […] When an underlying etiology for persistent hypereosinophilia is not identified despite thorough diagnostic evaluation, clinicians must consider the diagnosis of hypereosinophilic syndromes (HES), which comprise a heterogeneous group of uncommon disorders.

• #29 Eosinophilia: Symptoms and Causes | Doctor

  https://patient.info/doctor/eosinophilia

  Hypereosinophilic syndromes (HES) is characterized by: 1.5 x 109 eosinophils 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. […] Allergy diseases: asthma, urticaria, eczema, allergic rhinitis, angioneurotic oedema. […] Drug hypersensitivity. Drugs which more commonly cause eosinophilia include anticonvulsants, allopurinol, sulfonamides and certain antibiotics. […] Infections: in particular, parasitic infections including ascariasis, schistosomiasis, trichinellosis, visceral larva migrans, strongyloidiasis, echinococcosis, coccidioidomycosis.

• #30 Eosinophilia: Symptoms and Causes | Doctor

  https://patient.info/doctor/eosinophilia

  Hypereosinophilic syndromes (HES) is characterized by: 1.5 x 109 eosinophils 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. […] Allergy diseases: asthma, urticaria, eczema, allergic rhinitis, angioneurotic oedema. […] Drug hypersensitivity. Drugs which more commonly cause eosinophilia include anticonvulsants, allopurinol, sulfonamides and certain antibiotics. […] Infections: in particular, parasitic infections including ascariasis, schistosomiasis, trichinellosis, visceral larva migrans, strongyloidiasis, echinococcosis, coccidioidomycosis.

• #31 Practical approach to the patient with hypereosinophilia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2902584/

  An initial consideration of etiologies for eosinophilia needs to focus on several not uncommon causes. Helminthic parasites typically elicit IL-5-mediated eosinophil expansion. […] While it is assumed that eosinophilia associated with adverse drug reactions is IL-5 mediated, in many instances the mechanism and the organ-targeted involvements elicited by medications remain unclear. […] Besides these relatively common causes of eosinophilia, neoplastic diseases, including varied adenocarcinomas, some forms of Hodgkin’s disease, T cell lymphoma, and mastocytosis, may be associated with paraneoplastic eosinophilia, as noted above. […] When an underlying etiology for persistent hypereosinophilia is not identified despite thorough diagnostic evaluation, clinicians must consider the diagnosis of hypereosinophilic syndromes (HES), which comprise a heterogeneous group of uncommon disorders.

• #32 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-Causes-Eosinophilia.aspx

  Non-parasitic infestations such as Aspergillosis, Brucellosis, Chlamydial lung infection, Acute coccidiomycosis, Cat-scratch fever, Infectious mononucleosis, Mycobacterial infections. […] Other conditions that may be found in eosinophilia include: Peritoneal dialysis, Liver cirrhosis, Radiation, Certain cancers such as lung or pancreatic cancer, Hodgkins lymphoma, Non-Hodgkins lymphoma.

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

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

  Many conditions cause your eosinophil counts to increase in your blood. […] Problems with immune regulation can also cause eosinophilia, including autoimmune diseases like inflammatory bowel disease, autoimmune myocarditis, vasculitis and sarcoidosis. […] Blood cancers that make these cells inappropriately can also cause eosinophilia. […] Finally, genetic changes that are hereditary (passed on by your biological parents) can cause eosinophilia. […] Sometimes, eosinophils cause inflammation in specific areas of your body. When this happens, its called an eosinophilic disorder or hypereosinophilia syndrome (HES). […] Hypereosinophilic syndrome typically affects your heart, central nervous system, skin and respiratory tract.

• #34 Eosinophilia: Symptoms and Causes | Doctor

  https://patient.info/doctor/eosinophilia

  Neoplasia: […] Endocrine: adrenal insufficiency – eg, Addison’s disease. […] Skin disease – pemphigus, dermatitis herpetiformis, erythema multiforme. […] Lffler’s syndrome (accumulation of eosinophils in the lungs, due to parasitic infection). […] Lffler’s endocarditis (restrictive cardiomyopathy with eosinophilia). […] Irradiation. […] Post-splenectomy. […] Cholesterol emboli.

• #35 Hypereosinophilic syndrome – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hypereosinophilic-syndrome/symptoms-causes/syc-20352854

  Some varieties of hypereosinophilic syndrome tend to run in families. […] Other types have been associated with certain types of cancers, infections or other health problems.

• #36 Hypereosinophilic Syndrome – StatPearls – NCBI Bookshelf

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

  Based on the initial patient evaluation, HES can be classified into 5 clinically relevant variants: […] Primary/Neoplastic (HESN) […] Myeloid variants (M-HES): Classified into various subtypes, including platelet-derived growth factor receptor alpha FIP1L1-PDGFRA fusion gene (F/P pos variant), which occurs secondary to an interstitial chromosomal deletion on 4q12. […] T-cell lymphocytic variants (L-HES): Caused by aberrant IL-5-producing T-cells, such as CD3-CD4+ T cell-associated disease. […] Secondary/Reactive (HESR) […] Specific/defined hypereosinophilic syndromes secondary to an underlying condition such as an infectious or inflammatory process. […] Familial HES (HESFA) […] Namely when there is a family history of documented persistent hypereosinophilia of unknown cause. […] Idiopathic (IHES) […] Hypereosinophilia with no clear underlying cause associated with end-organ damage. […] Organ-Restricted HES […] Namely, when tissue hypereosinophilia is present, it causes end-organ damage, but HES blood criteria are unmet.

• #37 Hypereosinophilic syndrome – Wikipedia

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

  Eosinophilia in lymphocytic HES is caused by populations of activated T lymphocytes producing more eosinophil hematopoietins, specifically interleukin-5 (IL-5). […] Severe eosinophilia with an unknown etiology that manifests in successive generations is known as familial hypereosinophilia syndrome (HES).

• #38 Hypereosinophilic Syndrome – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/eosinophilic-disorders/hypereosinophilic-syndrome

  Patients with the lymphoproliferative variant also more often respond favorably to corticosteroids and occasionally develop T-cell lymphoma. […] Other hypereosinophilic syndrome variants include Gleich syndrome (episodic angioedema with eosinophilia), familial hypereosinophilic syndrome mapped to 5q 31-33, and other organ-specific syndromes. […] Death usually results from organ, particularly cardiac, dysfunction. […] Prognosis varies depending on response to therapy. […] Response to imatinib improves the prognosis among patients with the FIP1L1/PDGFRA-associated fusion gene and other responsive gene fusions.

• #39 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. […] Recent advances in underlying pathogenesis have established that what was once thought to be ”idiopathic” HES may in some cases be due to either primitive involvement of myeloid cells (primary HES), essentially due to occurrence of an interstitial chromosomal deletion on 4q12 leading to creation of the F/P fusion gene (CEL), or to increased interleukin (IL)-5 production by a clonally expanded T cell population (lymphocytic variant HES), most frequently characterized by a CD3-CD4+ phenotype, or due to other reactive causes (secondary HES) such as helminthic infection. […] However, in roughly 3/4 of cases, pathogenesis remains unknown, now defining idiopathic HES. […] A small subgroup of patients have HES that shows familial clustering (familial HES), presumably due to an as of yet unknown inherited gene.

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

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

  Hypereosinophilic syndromes (HES) are a rare group of blood disorders associated with an abnormally high number of white blood cells called eosinophils. […] Various factors can trigger the development of HES, including genetics, parasitic infections, drug hypersensitivity, blood cancers, and immunodeficiency disorders. […] Gene changes and underlying conditions can contribute to the development of hypereosinophilic syndrome, though the exact cause is not always clear. […] Gene fusions occur when two formerly separate genes merge into one hybrid (fusion) gene with features from both original genes. In HES, the fusion of the FIP1L1 and PDGFRA genes leads to the creation of proteins that trigger uncontrolled growth of eosinophils. […] Inherited gene mutations run in families. Familial HES occurs when mutations in the 5q31-q33 region of chromosome 5 lead to abnormal levels of a pro-inflammatory cytokine (a type of inflammatory protein) called interleukin-5, which controls the growth and mobilization of eosinophils.

• #41 French guidelines for the etiological workup of eosinophilia and the management of hypereosinophilic syndromes | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02696-4

  Eosinophils are produced in the bone marrow from the differentiation of hematopoietic stem cell progenitors. Their differentiation, maturation and release into the peripheral blood is orchestrated by a specific combination of transcription and growth factors, the most important being IL-5, IL-3 and GM-CSF. These cytokines can be produced by TH2-polarized CD4+T cells, type 2 innate lymphoid cells (ILC2s), mast cells and mesenchymal cells, as well as eosinophils themselves. […] The various causes of HE/HES are usually classified according to their underlying pathophysiological mechanisms. Thus, four major distinct clinical case definitions are usually distinguished: Clonal HE (previously myeloid variant of HE/HES), Reactive HE, HE of undetermined significance (HEus), Familial HE. […] Data regarding genetic factors predisposing to or responsible for HES are scarce, and no genome-wide association study has yet been performed. A JAK1 gain-of-function germline mutation was recently identified in a mother and her two sons whose clinical symptoms were consistent with multi-refractory systemic HES and who all responded to targeted treatment with a JAK inhibitor.

• #42 Hypereosinophilic Syndrome – StatPearls – NCBI Bookshelf

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

  Based on the initial patient evaluation, HES can be classified into 5 clinically relevant variants: […] Primary/Neoplastic (HESN) […] Myeloid variants (M-HES): Classified into various subtypes, including platelet-derived growth factor receptor alpha FIP1L1-PDGFRA fusion gene (F/P pos variant), which occurs secondary to an interstitial chromosomal deletion on 4q12. […] T-cell lymphocytic variants (L-HES): Caused by aberrant IL-5-producing T-cells, such as CD3-CD4+ T cell-associated disease. […] Secondary/Reactive (HESR) […] Specific/defined hypereosinophilic syndromes secondary to an underlying condition such as an infectious or inflammatory process. […] Familial HES (HESFA) […] Namely when there is a family history of documented persistent hypereosinophilia of unknown cause. […] Idiopathic (IHES) […] Hypereosinophilia with no clear underlying cause associated with end-organ damage. […] Organ-Restricted HES […] Namely, when tissue hypereosinophilia is present, it causes end-organ damage, but HES blood criteria are unmet.

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

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

  Finally, a good half of patients with HES remain unclassified, and present truly „idiopathic” hypereosinophilia. Among these, some present features of myeloproliferative disease similar to those encountered in F/P+ individuals, whereas others appear to have more of an „immuno-allergic” disease suggesting possible involvement of T cells. Further investigation of eosinophils and T cells in these idiopathic cases, will very likely lead to identification of novel molecular mechanisms ultimately leading to hypereosinophilia.

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

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

  Finally, a good half of patients with HES remain unclassified, and present truly „idiopathic” hypereosinophilia. Among these, some present features of myeloproliferative disease similar to those encountered in F/P+ individuals, whereas others appear to have more of an „immuno-allergic” disease suggesting possible involvement of T cells. Further investigation of eosinophils and T cells in these idiopathic cases, will very likely lead to identification of novel molecular mechanisms ultimately leading to hypereosinophilia.

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

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

  Finally, a good half of patients with HES remain unclassified, and present truly „idiopathic” hypereosinophilia. Among these, some present features of myeloproliferative disease similar to those encountered in F/P+ individuals, whereas others appear to have more of an „immuno-allergic” disease suggesting possible involvement of T cells. Further investigation of eosinophils and T cells in these idiopathic cases, will very likely lead to identification of novel molecular mechanisms ultimately leading to hypereosinophilia.

• #46 Hypereosinophilic Syndrome – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/eosinophilic-disorders/hypereosinophilic-syndrome

  Hypereosinophilic syndrome is a condition characterized by peripheral blood eosinophilia with manifestations of organ system involvement or dysfunction directly related to eosinophilia in the absence of parasitic, allergic, or other secondary causes of eosinophilia. […] Hypereosinophilic syndrome was previously considered to be idiopathic, but molecular characterization has revealed that many cases have specific clonal disorders. […] One limitation of the traditional definition is that it does not include those patients with some of the same abnormalities (eg, chromosomal defects) that are known causes of hypereosinophilic syndrome but who do not fulfill the traditional hypereosinophilic syndrome definition for degree or duration of eosinophilia. […] Eosinophilia of any etiology can cause the same types of tissue damage.

• #47 Hypereosinophilic Syndrome | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/1688726/all/Hypereosinophilic_Syndrome?q=Chronic+Leukemia%2C+Myelogenous

  Primary molecular defect resulting in clonal eosinophilic proliferation and/or overproduction or functional abnormalities of eosinophilopoietic cytokines and/or defects in normal suppressive regulation of eosinophilopoiesis. […] Three hematopoietic cytokines: IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate bone marrow myeloid progenitors to overproduce eosinophils; IL-5 is most specific for eosinophil differentiation. […] HES: Eosinophils infiltrate organs and release toxic granules containing major basic protein, eosinophil peroxidase, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), Charcot-Leyden crystals, VIP, and substance P; neurotoxic, cytotoxic, and prothrombotic; creates oxidative burst, reactive oxygen species. […] EDN and ECP activate fibroblasts: fibrosis and organ dysfunction.

• #48 Hypereosinophilic Syndrome | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/1688726/all/Hypereosinophilic_Syndrome?q=Chronic+Leukemia%2C+Myelogenous

  Primary molecular defect resulting in clonal eosinophilic proliferation and/or overproduction or functional abnormalities of eosinophilopoietic cytokines and/or defects in normal suppressive regulation of eosinophilopoiesis. […] Three hematopoietic cytokines: IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate bone marrow myeloid progenitors to overproduce eosinophils; IL-5 is most specific for eosinophil differentiation. […] HES: Eosinophils infiltrate organs and release toxic granules containing major basic protein, eosinophil peroxidase, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), Charcot-Leyden crystals, VIP, and substance P; neurotoxic, cytotoxic, and prothrombotic; creates oxidative burst, reactive oxygen species. […] EDN and ECP activate fibroblasts: fibrosis and organ dysfunction.

• #49 Hypereosinophilic Syndrome | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/1688726/all/Hypereosinophilic_Syndrome?q=Chronic+Leukemia%2C+Myelogenous

  Primary molecular defect resulting in clonal eosinophilic proliferation and/or overproduction or functional abnormalities of eosinophilopoietic cytokines and/or defects in normal suppressive regulation of eosinophilopoiesis. […] Three hematopoietic cytokines: IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate bone marrow myeloid progenitors to overproduce eosinophils; IL-5 is most specific for eosinophil differentiation. […] HES: Eosinophils infiltrate organs and release toxic granules containing major basic protein, eosinophil peroxidase, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), Charcot-Leyden crystals, VIP, and substance P; neurotoxic, cytotoxic, and prothrombotic; creates oxidative burst, reactive oxygen species. […] EDN and ECP activate fibroblasts: fibrosis and organ dysfunction.

• #50 Hypereosinophilic Syndrome – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/eosinophilic-disorders/hypereosinophilic-syndrome

  Patients with the myeloproliferative subtype often develop endomyocardial fibrosis and may rarely develop acute myeloid leukemia or acute lymphoblastic leukemia. […] A small proportion of patients with the myeloproliferative variant of hypereosinophilic syndrome have cytogenetic changes involving platelet-derived growth factor receptor beta (PDGFRB) and may also be responsive to tyrosine kinase inhibitors such as imatinib. […] Other cytogenetic abnormalities include rearrangement of the gene for fibroblast growth factor receptor 1 (FGFR1) or Janus kinase 2 (PCM1-JAK2). […] Recently, ETV6-ABL1 and various FLT3 fusions have been added to the gene rearrangements associated with hypereosinophilia. […] The lymphoproliferative variant is associated with a clonal population of T cells with aberrant phenotype.

• #51 Hypereosinophilic Syndrome – Ask Hematologist | Understand Hematology

  https://askhematologist.com/hypereosinophilic-syndrome/

  The myeloproliferative variant is often associated with a small interstitial deletion in chromosome 4 at the CHIC2 site that causes the FIP1L1/PDGFRA-associated fusion gene (which has tyrosine kinase activity that can transform hematopoietic cells). […] A small proportion of patients with the myeloproliferative variant of the hypereosinophilic syndrome have cytogenetic changes involving platelet-derived growth factor receptor beta (PDGFRB) and may also be responsive to tyrosine kinase inhibitors such as imatinib. […] The lymphoproliferative variant is associated with a clonal population of T cells with an aberrant phenotype. […] Other HES variants include chronic eosinophilic leukemia, Gleich syndrome (cyclical eosinophilia and angioedema), familial hypereosinophilic syndrome mapped to 5q 31-33, and other organ-specific syndromes. […] Eosinophils can form aggregates that occlude small blood vessels, causing tissue ischemia and microinfarctions.

• #52 Idiopathic Hypereosinophilic Syndrome as a Rare Cause of Stroke: A Case Report | 2021, Volume 27 – Issue 4 | Turkish Journal of Neurology

  https://tjn.org.tr/full-text/144/eng

  Hypereosinophilic syndrome (HES) is a rare hematological disease that causes organ damage by eosinophil infiltration in the tissue with increased eosinophil production in the bone marrow. HES is a rare but important cause of stroke. […] The current cerebrovascular event of the patient was thought to be due to eosinophilia. […] Cerebral infarction develops with endomyocardial thromboembolism due to vascular endothelium toxicity after the release of mediators by eosinophils. […] Hypereosinophilia should be suspected to be a cause of cerebrovascular disease especially in patients with ischemic lesions at a young age with borderline zones and multiple locations. […] The characteristic features of a stroke due to HES are the emergence of multiple ischemiae in different vascular areas. HES is a syndrome that should be kept in mind that can change the treatment options in patients with bilateral, multiple localization, and border area infarction with unknown etiology.

• #53 Hypereosinophilic Syndrome: What It Is, Causes, Complications

  https://www.verywellhealth.com/hypereosinophilic-syndrome-7564454

  The only known risk factor for developing hypereosinophilic syndrome is being an adult male between the ages of 20 and 50. About 90% of HES cases are males in middle age. […] Hypereosinophilic syndrome is not leukemia. But some people who develop hypereosinophilic syndrome discover that they have a blood disorder commonly cancer of the white blood cells called leukemia. It may take several years after hypereosinophilic syndrome is first found for healthcare providers to uncover leukemia. […] The cause of hypereosinophilic syndromes is often unknown, but some have a genetic origin.

• #54 Hypereosinophilic Syndrome: What It Is, Causes, Complications

  https://www.verywellhealth.com/hypereosinophilic-syndrome-7564454

  The only known risk factor for developing hypereosinophilic syndrome is being an adult male between the ages of 20 and 50. About 90% of HES cases are males in middle age. […] Hypereosinophilic syndrome is not leukemia. But some people who develop hypereosinophilic syndrome discover that they have a blood disorder commonly cancer of the white blood cells called leukemia. It may take several years after hypereosinophilic syndrome is first found for healthcare providers to uncover leukemia. […] The cause of hypereosinophilic syndromes is often unknown, but some have a genetic origin.

• #55 Hypereosinophilic syndrome – Two cases with varied manifestations – Journal of Skin and Sexually Transmitted Diseases

  https://jsstd.org/hypereosinophilic-syndrome-two-cases-with-varied-manifestations/

  HES is classified into myeloproliferative, lymphocytic, undefined, familial, overlap, and associated types. […] Myeloproliferative HES is often seen in males, may or may not be associated with positive FIP1L1-PDGFRA mutation and commonly accompanied by cardiac involvement. […] In contrast to myeloid HES, lymphocytic HES shows no sex predilection. […] Mucocutaneous manifestations described in HES are pruritus, angioedema, urticaria, purpuric macules, papules, plaques, nodules, mucosal ulcers, gangrene, livedo reticularis, Raynauds phenomenon, vesicles, eczematous lesions, and vasculitis. […] HES should be a differential diagnosis in all cases of persistent eosinophilia. A full workup is mandatory before making a diagnosis of HES. Failure to detect the condition early may lead to irreversible cardiac damage.

• #56

  https://journals.lww.com/ijo/fulltext/2018/66100/a_rare_case_of_hypereosinophilic_syndrome.41.aspx

  Hypereosinophilic syndrome (HES) is a spectrum of myeloproliferative disorder, which is characterized by persistent and marked blood eosinophilia and damage to multiple organs due to eosinophilic infiltration. […] Idiopathic HES is identified after ruling out all other causes of eosinophilia. […] The term idiopathic HES as defined by Chusid et al. was characterized by three criteria: (1) eosinophil count greater than 1,500 cells/L persisting longer than 6 months, (2) single or multiple organ system dysfunction attributable to cytotoxic injury by eosinophils, and (3) without an identifiable etiology to explain the eosinophilia. […] Inspite of significant amount progress in the understanding of the pathogenesis of HES, our knowledge is insufficient in formulating a new comprehensive definition of HES based on the etiology.

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

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

  Eosinophils belong to the myeloid lineage, and differentiate from myeloid progenitors (GEMM-CFU) in bone marrow. Among the three cytokines that act as eosinophil growth factors and apoptosis inhibitors, i.e. granulocyte-macrophage colony stimulating factor (GM-CSF), IL-3, and IL-5, only the latter displays specificity for eosinophils. The major source of this eosinophil-specific cytokine is represented by so-called „type 2” helper T cells. Recent studies based on material from patients fulfilling Chusid’s HES diagnostic criteria have shown that two distinct underlying mechanisms may lead to chronic unexplained hypereosinophilia in HES patient subgroups: occurrence of a sporadic hematopoetic stem cell mutation, leading to primitive clonal expansion of cells belonging to the myeloid lineage with preferential eosinophilic differentiation (as such, hypereosinophilia belongs to the group of chronic myeloproliferative disorders), or overproduction of eosinophilopoietic cytokine(s) by an activated population of T cells (in the „lymphocytic variant” of HES, or L-HES).

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

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

  Finally, a good half of patients with HES remain unclassified, and present truly „idiopathic” hypereosinophilia. Among these, some present features of myeloproliferative disease similar to those encountered in F/P+ individuals, whereas others appear to have more of an „immuno-allergic” disease suggesting possible involvement of T cells. Further investigation of eosinophils and T cells in these idiopathic cases, will very likely lead to identification of novel molecular mechanisms ultimately leading to hypereosinophilia.

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