Materiały źródłowe

• #1 How I treat hypereosinophilic syndromes

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4551360/

  Hypereosinophilic syndromes (HESs) are a group of rare disorders characterized by peripheral blood eosinophilia of 1.5 109/L or higher and evidence of end organ manifestations attributable to the eosinophilia and not otherwise explained in the clinical setting. […] Although corticosteroids remain the first-line therapy for most forms of HESs, the availability of an increasing number of novel therapeutic agents, including tyrosine kinase inhibitors and monoclonal antibodies, has necessarily altered the approach to treatment of HESs. […] When life-threatening manifestations are present or imminent, as in the case presented, high-dose corticosteroid therapy should be initiated immediately. Recommended dosing ranges from 1 mg/kg prednisone to 1 g methylprednisolone depending on the severity of the clinical manifestations.

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

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

  Treatment may include corticosteroids and sometimes imatinib but depends on the specific subtype of hypereosinophilic syndrome. […] Corticosteroids for hypereosinophilia and often for ongoing treatment of organ damage. […] Imatinib for patients with the FIP1L1/PDGFRA-associated fusion gene or other similar gene fusions. […] Sometimes medications to control eosinophil counts (eg, hydroxyurea, interferon alfa, etoposide, cladribine). […] There is no set level of eosinophilia at which organ damage occurs or at which treatment must be started, but most experts recommend starting therapy at an absolute eosinophil count of 1500 to 2000 eosinophils/mcL (1.5 to 2 109/L). […] For patients with very severe eosinophilia, complications of hyperleukocytosis such as dyspnea or mental status changes may occur (usually in patients with eosinophilic leukemia). In these cases, high-dose corticosteroids (eg, ranging from prednisone 1 mg/kg or equivalent to 1 gram of methylprednisolone) should be initiated as soon as possible.

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

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

  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. […] If you have no symptoms and your eosinophil count is low enough, you might require no treatment other than close monitoring for any changes related to HES. […] Systemic corticosteroids, such as prednisone, are the first line treatment. Other treatment options include: Hydroxyurea (Droxia, Hydrea, Siklos), Imatinib (Gleevec), Vincristine. […] Because HES can increase your risk of blood clots, you might also be prescribed blood-thinning medications such as warfarin (Coumadin). […] If nothing else has worked, your doctor might suggest a stem cell or bone marrow transplant.

• #4 Hypereosinophilic syndromes: Treatment – UpToDate

  https://www.uptodate.com/contents/hypereosinophilic-syndromes-treatment

  Hypereosinophilic syndromes: Treatment […] The urgency of treatment and choice of therapy is based on the patient’s presentation, as well as laboratory findings and the results of mutational analysis. […] The overall goals of therapy are reduction of the absolute eosinophil count (AEC), amelioration of signs and symptoms, and prevention of disease progression. […] The urgency with which patients are treated depends on the severity of hypereosinophilia (HE) and the presence of signs and symptoms of the disease.

• #5 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  Whether and how to treat symptomatic hypereosinophilic syndrome depends on the clinical presentation, laboratory findings, and mutational analysis. Currently, treating asymptomatic patients with hypereosinophilic syndrome is not recommended, as treatment itself is not without risks. Such patients are closely monitored with serum troponin measurements every 3-6 months, and echocardiography and pulmonary function tests every 6-12 months. […] In contrast, cases of hypereosinophilic syndrome with myeloproliferative features, particularly those with FIP1L1/PDGFRA mutation, should be treated aggressively. These patients carry a worse prognosis without treatment. […] In all patients without FIP1L1/PDGFRA mutation, glucocorticoids are the first-line therapy. About one third of these cases do not respond to steroids. In such patients, interferon alpha and hydroxyurea are the recommended second-line drugs. For third-line therapy, high-dose (400 mg/d) imatinib is the treatment of choice.

• #6 How I treat hypereosinophilic syndromes

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4551360/

  Hypereosinophilic syndromes (HESs) are a group of rare disorders characterized by peripheral blood eosinophilia of 1.5 109/L or higher and evidence of end organ manifestations attributable to the eosinophilia and not otherwise explained in the clinical setting. […] Although corticosteroids remain the first-line therapy for most forms of HESs, the availability of an increasing number of novel therapeutic agents, including tyrosine kinase inhibitors and monoclonal antibodies, has necessarily altered the approach to treatment of HESs. […] When life-threatening manifestations are present or imminent, as in the case presented, high-dose corticosteroid therapy should be initiated immediately. Recommended dosing ranges from 1 mg/kg prednisone to 1 g methylprednisolone depending on the severity of the clinical manifestations.

• #7 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

  Corticosteroids are the first-line option for patients with idiopathic HES (HES). The recommended dosage for adults ranges from 40 mg/day to 1 mg/kg/day of prednisone given orally; for more severe cases, 1 g of methylprednisolone per day should be used. Treatment with corticosteroids induces a rapid reduction in the eosinophil count in most patients; however, the tapering of corticosteroids usually needs to be prolonged over months (median maintenance dose, 10 mg/day). Some authors have suggested that the response to corticosteroids can be predicted based on the disease subtype, with myeloid and lymphocytic HES variants having worse response compared to HES, EGPA, and HES with single-organ involvement. […] The persistence of blood eosinophilia despite the administration of corticosteroids suggests that treatment needs to be intensified with the addition of a second medication. Hydroxyurea may be used as a first-line therapy in combination with corticosteroids, or as monotherapy in non-respondents. Hydroxyurea effectively controls leukocytes and eosinophils count, but there is no evidence of an influence on the natural history of HES. A second-line option for patients who fail to respond to, or do not tolerate, corticosteroids and hydroxyurea is interferon-α (IFN-α). IFN-α can produce hematologic or cytogenetic remission, as well as reverse organ injury. In patients with aggressive disease, bone marrow/peripheral blood allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted with variable results. Leukapheresis can elicit transient reductions in high leukocyte and eosinophil counts but is ineffective in the long term. Anti-platelet and anticoagulant agents may be useful for preventing thromboembolism; however, a standard approach regulating their use as primary prevention in patients with HES is currently lacking. Other immunosuppressive drugs such as cyclosporine, azathioprine, and methotrexate can be used in patients with HES to control the disease and as steroid-sparing drugs.

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

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

  Treatment may include corticosteroids and sometimes imatinib but depends on the specific subtype of hypereosinophilic syndrome. […] Corticosteroids for hypereosinophilia and often for ongoing treatment of organ damage. […] Imatinib for patients with the FIP1L1/PDGFRA-associated fusion gene or other similar gene fusions. […] Sometimes medications to control eosinophil counts (eg, hydroxyurea, interferon alfa, etoposide, cladribine). […] There is no set level of eosinophilia at which organ damage occurs or at which treatment must be started, but most experts recommend starting therapy at an absolute eosinophil count of 1500 to 2000 eosinophils/mcL (1.5 to 2 109/L). […] For patients with very severe eosinophilia, complications of hyperleukocytosis such as dyspnea or mental status changes may occur (usually in patients with eosinophilic leukemia). In these cases, high-dose corticosteroids (eg, ranging from prednisone 1 mg/kg or equivalent to 1 gram of methylprednisolone) should be initiated as soon as possible.

• #9 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  Due to the rapidity and reliability of its effect, a 5-day course of prednisone (1 mg/kg/d or 60 mg/d) is the initial treatment of choice for all FIP1L1/PGDFRA negative patients. […] Almost 70% of patients with hypereosinophilic syndrome respond well to steroid therapy, especially those who present with urticaria and high IgE levels. […] Imatinib mesylate (Gleevec) is the drug of choice for hypereosinophilic syndrome with FIP1L1/PDGFRA. […] In patients with hypereosinophilic syndrome with FIP1L1/PDGFRA, imatinib induces clinical hematologic and molecular remission in the majority of cases. […] Interferon alpha is a second-line drug of choice for patients whose condition does not respond to glucocorticoids. Hydroxyurea has also demonstrated efficacy for steroid-refractory cases. […] Alemtuzumab, an anti-CD52 monoclonal antibody, has been shown to control symptoms as well as eosinophilia in patients with refractory hypereosinophilic syndrome. […] Periodically observe patients with hypereosinophilic syndrome to confirm that the eosinophilia is controlled and that no evidence of new or worsening organ involvement occurs.

• #10 Hypereosinophilic syndrome – Wikipedia

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

  Treatment Corticosteroids, Imatinib, medications to control eosinophil counts, and supportive care. […] If left untreated, HES is progressive and fatal. It is treated with glucocorticoids such as prednisone. […] The addition of the monoclonal antibody mepolizumab may reduce the dose of glucocorticoids. […] As a first-line treatment for HES patients’ symptoms, corticosteroids are recommended. […] Because high-dose prednisone rapidly lowers eosinophil levels, it is usually started at a dose of 1 mg/kg/day. […] Upon achieving appropriate control over eosinophilia, the medication can be gradually reduced. […] Steroid-refractory HES has been managed with a variety of cytotoxic treatments. […] Out of all of them, hydroxyurea has been researched the most and has been linked to few side effects at doses as high as 2 g per day.

• #11 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

  Corticosteroids are the first-line option for patients with idiopathic HES (HES). The recommended dosage for adults ranges from 40 mg/day to 1 mg/kg/day of prednisone given orally; for more severe cases, 1 g of methylprednisolone per day should be used. Treatment with corticosteroids induces a rapid reduction in the eosinophil count in most patients; however, the tapering of corticosteroids usually needs to be prolonged over months (median maintenance dose, 10 mg/day). Some authors have suggested that the response to corticosteroids can be predicted based on the disease subtype, with myeloid and lymphocytic HES variants having worse response compared to HES, EGPA, and HES with single-organ involvement. […] The persistence of blood eosinophilia despite the administration of corticosteroids suggests that treatment needs to be intensified with the addition of a second medication. Hydroxyurea may be used as a first-line therapy in combination with corticosteroids, or as monotherapy in non-respondents. Hydroxyurea effectively controls leukocytes and eosinophils count, but there is no evidence of an influence on the natural history of HES. A second-line option for patients who fail to respond to, or do not tolerate, corticosteroids and hydroxyurea is interferon-α (IFN-α). IFN-α can produce hematologic or cytogenetic remission, as well as reverse organ injury. In patients with aggressive disease, bone marrow/peripheral blood allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted with variable results. Leukapheresis can elicit transient reductions in high leukocyte and eosinophil counts but is ineffective in the long term. Anti-platelet and anticoagulant agents may be useful for preventing thromboembolism; however, a standard approach regulating their use as primary prevention in patients with HES is currently lacking. Other immunosuppressive drugs such as cyclosporine, azathioprine, and methotrexate can be used in patients with HES to control the disease and as steroid-sparing drugs.

• #12

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

  In December 2021, the IL5 antagonist mepolizumab was also approved for treatment of HES. […] Experience has shown that OCS can rarely be completely discontinued in HES, and most patients require low-dose OCS baseline therapy to control disease activity despite the addition of immunosuppressants and/or biologicals. […] Specific tyrosine kinase inhibitors (TKIs) are available for the treatment of clonal eosinophilia, depending on the underlying fusion gene. […] In case of clonal eosinophilia, a durable response to OCS is not expected, so that initiation and response or non-response occasionally has diagnostic value. […] For adequate treatment of HES, careful clarification of the qualitative and quantitative organ involvement pattern is essential. If therapy is required (symptoms, organ involvement), OCS-sparing immunosuppression is administered in addition to initial OCS administration (analogous to other autoimmune diseases), if necessary. […] Recently, the IL5 antibody mepolizumab was approved for treatment of HES.

• #13 Effective Hypereosinophilic Syndrome Treatment Options – Acibadem Health Point – ACIBADEM Hospitals – Acibadem Health Group

  https://www.acibademhealthpoint.com/effective-hypereosinophilic-syndrome-treatment-options/

  Corticosteroids: Usually the first choice, they lower eosinophil levels fast and ease symptoms. But using them for a long time can cause problems like weight gain and more infections. […] Other than medicines, lifestyle changes are important in the start of HES care. They aim to make health and well-being better. […] Both taking medicines and making lifestyle changes are key to dealing with HES at the start. They work together to give the best care possible. […] Corticosteroids are key in treating Hypereosinophilic Syndrome (HES). They help lower symptoms and stop problems by lowering inflammation. […] They lower the immune system. This cuts down on eosinophils, a type of white blood cell that gets too high in HES. This drop in cells helps lessen swelling and other symptoms. The aim is to handle the disease well, making life better for the patient.

• #14 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  For patients with FIP1L1/PDGFRA mutation, imatinib is the drug of choice. The response rate in these cases approaches 100% in various studies. […] Mepolizumab, a humanized monoclonal antibody specific for interleukin-5 (IL-5), is the first treatment shown to reduce disease flares in patients with FIP1L1/PDGFRA-negative hypereosinophilic syndrome. […] For hypereosinophilic syndrome that is refractory to the usual treatments, chemotherapeutic agents that have been used with some success include chlorambucil, etoposide, vincristine, and cladribine and cytarabine. […] Alternatively, in refractory cases, particularly those resistant to imatinib therapy, hematopoietic stem cell transplantation (HSCT) has been shown to reverse the organ dysfunction. […] Leukapheresis is indicated as an emergency therapy in hypereosinophilic syndrome to control symptoms due to hyperleukocytosis.

• #15 How I treat hypereosinophilic syndromes

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4551360/

  If the eosinophil count and symptoms do not improve after 1 to 2 days of high-dose corticosteroid therapy, a second agent should be added to rapidly lower the eosinophil count. […] The most commonly used second-line therapies are hydroxyurea (1-2 g orally daily) and interferon- (1-3 mU subcutaneously daily), each of which is effective in 30% of patients. […] Corticosteroids remain the mainstay of therapy for idiopathic HES. […] High-dose corticosteroids are often effective in the short-term reduction of eosinophilia and clinical manifestations in patients with PDGFR-negative M-HES and are useful in the initial management of such patients. […] Patients with documented rearrangements or mutations involving PDGFRA should be treated with imatinib mesylate (100-400 mg by mouth daily). […] A number of agents that target eosinophils are currently in clinical development for the treatment of eosinophilic disorders. […] Mepolizumab is currently available only on clinical protocols for patients with life-threatening HES refractory to standard therapies (as in the case presented) or with EGPA.

• #16 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

  Imatinib is an effective treatment in patients with HES caused by a PDGFRA/B-rearranged eosinophilic neoplasm. Patients with HE and the rearranged clonal marker FIP1L1-PDGFRA are included in the category “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion” and usually present an excellent response to imatinib. Most patients achieve molecular remission with a 100 mg/day dose, while the maintenance dose may vary between 100 and 400 mg/day. For patients with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion with eosinophilia and the PDGFRB rearrangement, the imatinib recommended dose is 400 mg/day for inducing remission and 100 mg/day for maintenance. Imatinib’s safety profile in eosinophilic disorders aligns with the good tolerability seen in CML. A few cases of cardiogenic shock associated with imatinib have, however, been described. The FGFR1 inhibitor pemigatinib has recently been approved by the FDA for the treatment of patients with myeloid/lymphoid neoplasms with FGFR1 rearrangement. The JAK1/JAK2 inhibitor ruxolitinib is currently under investigation in HES and primary eosinophilic disorders. Additional tyrosine kinase inhibitor therapies targeting JAK2 and FLT3 have shown promising results. Lastly, dasatinib, an experimental anti-cancer drug designed to block the function of BCR-ABL, has been recently evaluated in several myeloproliferative disorders, including HES.

• #17 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

  Imatinib is an effective treatment in patients with HES caused by a PDGFRA/B-rearranged eosinophilic neoplasm. Patients with HE and the rearranged clonal marker FIP1L1-PDGFRA are included in the category “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion” and usually present an excellent response to imatinib. Most patients achieve molecular remission with a 100 mg/day dose, while the maintenance dose may vary between 100 and 400 mg/day. For patients with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion with eosinophilia and the PDGFRB rearrangement, the imatinib recommended dose is 400 mg/day for inducing remission and 100 mg/day for maintenance. Imatinib’s safety profile in eosinophilic disorders aligns with the good tolerability seen in CML. A few cases of cardiogenic shock associated with imatinib have, however, been described. The FGFR1 inhibitor pemigatinib has recently been approved by the FDA for the treatment of patients with myeloid/lymphoid neoplasms with FGFR1 rearrangement. The JAK1/JAK2 inhibitor ruxolitinib is currently under investigation in HES and primary eosinophilic disorders. Additional tyrosine kinase inhibitor therapies targeting JAK2 and FLT3 have shown promising results. Lastly, dasatinib, an experimental anti-cancer drug designed to block the function of BCR-ABL, has been recently evaluated in several myeloproliferative disorders, including HES.

• #18 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  For patients with FIP1L1/PDGFRA mutation, imatinib is the drug of choice. The response rate in these cases approaches 100% in various studies. […] Mepolizumab, a humanized monoclonal antibody specific for interleukin-5 (IL-5), is the first treatment shown to reduce disease flares in patients with FIP1L1/PDGFRA-negative hypereosinophilic syndrome. […] For hypereosinophilic syndrome that is refractory to the usual treatments, chemotherapeutic agents that have been used with some success include chlorambucil, etoposide, vincristine, and cladribine and cytarabine. […] Alternatively, in refractory cases, particularly those resistant to imatinib therapy, hematopoietic stem cell transplantation (HSCT) has been shown to reverse the organ dysfunction. […] Leukapheresis is indicated as an emergency therapy in hypereosinophilic syndrome to control symptoms due to hyperleukocytosis.

• #19 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

  Imatinib is an effective treatment in patients with HES caused by a PDGFRA/B-rearranged eosinophilic neoplasm. Patients with HE and the rearranged clonal marker FIP1L1-PDGFRA are included in the category “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion” and usually present an excellent response to imatinib. Most patients achieve molecular remission with a 100 mg/day dose, while the maintenance dose may vary between 100 and 400 mg/day. For patients with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion with eosinophilia and the PDGFRB rearrangement, the imatinib recommended dose is 400 mg/day for inducing remission and 100 mg/day for maintenance. Imatinib’s safety profile in eosinophilic disorders aligns with the good tolerability seen in CML. A few cases of cardiogenic shock associated with imatinib have, however, been described. The FGFR1 inhibitor pemigatinib has recently been approved by the FDA for the treatment of patients with myeloid/lymphoid neoplasms with FGFR1 rearrangement. The JAK1/JAK2 inhibitor ruxolitinib is currently under investigation in HES and primary eosinophilic disorders. Additional tyrosine kinase inhibitor therapies targeting JAK2 and FLT3 have shown promising results. Lastly, dasatinib, an experimental anti-cancer drug designed to block the function of BCR-ABL, has been recently evaluated in several myeloproliferative disorders, including HES.

• #20 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  Due to the rapidity and reliability of its effect, a 5-day course of prednisone (1 mg/kg/d or 60 mg/d) is the initial treatment of choice for all FIP1L1/PGDFRA negative patients. […] Almost 70% of patients with hypereosinophilic syndrome respond well to steroid therapy, especially those who present with urticaria and high IgE levels. […] Imatinib mesylate (Gleevec) is the drug of choice for hypereosinophilic syndrome with FIP1L1/PDGFRA. […] In patients with hypereosinophilic syndrome with FIP1L1/PDGFRA, imatinib induces clinical hematologic and molecular remission in the majority of cases. […] Interferon alpha is a second-line drug of choice for patients whose condition does not respond to glucocorticoids. Hydroxyurea has also demonstrated efficacy for steroid-refractory cases. […] Alemtuzumab, an anti-CD52 monoclonal antibody, has been shown to control symptoms as well as eosinophilia in patients with refractory hypereosinophilic syndrome. […] Periodically observe patients with hypereosinophilic syndrome to confirm that the eosinophilia is controlled and that no evidence of new or worsening organ involvement occurs.

• #21 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

  Corticosteroids are the first-line option for patients with idiopathic HES (HES). The recommended dosage for adults ranges from 40 mg/day to 1 mg/kg/day of prednisone given orally; for more severe cases, 1 g of methylprednisolone per day should be used. Treatment with corticosteroids induces a rapid reduction in the eosinophil count in most patients; however, the tapering of corticosteroids usually needs to be prolonged over months (median maintenance dose, 10 mg/day). Some authors have suggested that the response to corticosteroids can be predicted based on the disease subtype, with myeloid and lymphocytic HES variants having worse response compared to HES, EGPA, and HES with single-organ involvement. […] The persistence of blood eosinophilia despite the administration of corticosteroids suggests that treatment needs to be intensified with the addition of a second medication. Hydroxyurea may be used as a first-line therapy in combination with corticosteroids, or as monotherapy in non-respondents. Hydroxyurea effectively controls leukocytes and eosinophils count, but there is no evidence of an influence on the natural history of HES. A second-line option for patients who fail to respond to, or do not tolerate, corticosteroids and hydroxyurea is interferon-α (IFN-α). IFN-α can produce hematologic or cytogenetic remission, as well as reverse organ injury. In patients with aggressive disease, bone marrow/peripheral blood allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted with variable results. Leukapheresis can elicit transient reductions in high leukocyte and eosinophil counts but is ineffective in the long term. Anti-platelet and anticoagulant agents may be useful for preventing thromboembolism; however, a standard approach regulating their use as primary prevention in patients with HES is currently lacking. Other immunosuppressive drugs such as cyclosporine, azathioprine, and methotrexate can be used in patients with HES to control the disease and as steroid-sparing drugs.

• #22 How I treat hypereosinophilic syndromes

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4551360/

  If the eosinophil count and symptoms do not improve after 1 to 2 days of high-dose corticosteroid therapy, a second agent should be added to rapidly lower the eosinophil count. […] The most commonly used second-line therapies are hydroxyurea (1-2 g orally daily) and interferon- (1-3 mU subcutaneously daily), each of which is effective in 30% of patients. […] Corticosteroids remain the mainstay of therapy for idiopathic HES. […] High-dose corticosteroids are often effective in the short-term reduction of eosinophilia and clinical manifestations in patients with PDGFR-negative M-HES and are useful in the initial management of such patients. […] Patients with documented rearrangements or mutations involving PDGFRA should be treated with imatinib mesylate (100-400 mg by mouth daily). […] A number of agents that target eosinophils are currently in clinical development for the treatment of eosinophilic disorders. […] Mepolizumab is currently available only on clinical protocols for patients with life-threatening HES refractory to standard therapies (as in the case presented) or with EGPA.

• #23 Hypereosinophilic Syndrome Medication: Corticosteroids, Antineoplastic Agents, Immunomodulators, Interleukin Inhibitors

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

  The goals of pharmacotherapy in patients with hypereosinophilic syndrome (HES) are to reduce morbidity and to prevent complications. Glucocorticoids are the first-line therapy in patients without the FIP1L1/PDGFRA mutation, while imatinib is the first-line choice in patients with the FIP1L1/PDGFRA mutation. Mepolizumab is approved for use in adults and children aged 12 years and older with HES for 6 months or longer without an identifiable nonhematologic secondary cause. A variety of second-line agents may be used for refractory cases. […] Initial DOC. Once eosinophils are suppressed, the dose may be slowly tapered. Patients whose condition responds to steroids tend to have a better prognosis. […] Second line of treatment. Goal is to reduce total white blood cell (WBC) count to 10,000 cells/L. One week of therapy may be required before a reduction of the eosinophil count is observed. Anemia and thrombocytopenia are common complications associated with this drug.

• #24 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  Due to the rapidity and reliability of its effect, a 5-day course of prednisone (1 mg/kg/d or 60 mg/d) is the initial treatment of choice for all FIP1L1/PGDFRA negative patients. […] Almost 70% of patients with hypereosinophilic syndrome respond well to steroid therapy, especially those who present with urticaria and high IgE levels. […] Imatinib mesylate (Gleevec) is the drug of choice for hypereosinophilic syndrome with FIP1L1/PDGFRA. […] In patients with hypereosinophilic syndrome with FIP1L1/PDGFRA, imatinib induces clinical hematologic and molecular remission in the majority of cases. […] Interferon alpha is a second-line drug of choice for patients whose condition does not respond to glucocorticoids. Hydroxyurea has also demonstrated efficacy for steroid-refractory cases. […] Alemtuzumab, an anti-CD52 monoclonal antibody, has been shown to control symptoms as well as eosinophilia in patients with refractory hypereosinophilic syndrome. […] Periodically observe patients with hypereosinophilic syndrome to confirm that the eosinophilia is controlled and that no evidence of new or worsening organ involvement occurs.

• #25 How I treat hypereosinophilic syndromes

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4551360/

  If the eosinophil count and symptoms do not improve after 1 to 2 days of high-dose corticosteroid therapy, a second agent should be added to rapidly lower the eosinophil count. […] The most commonly used second-line therapies are hydroxyurea (1-2 g orally daily) and interferon- (1-3 mU subcutaneously daily), each of which is effective in 30% of patients. […] Corticosteroids remain the mainstay of therapy for idiopathic HES. […] High-dose corticosteroids are often effective in the short-term reduction of eosinophilia and clinical manifestations in patients with PDGFR-negative M-HES and are useful in the initial management of such patients. […] Patients with documented rearrangements or mutations involving PDGFRA should be treated with imatinib mesylate (100-400 mg by mouth daily). […] A number of agents that target eosinophils are currently in clinical development for the treatment of eosinophilic disorders. […] Mepolizumab is currently available only on clinical protocols for patients with life-threatening HES refractory to standard therapies (as in the case presented) or with EGPA.

• #26 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

  Corticosteroids are the first-line option for patients with idiopathic HES (HES). The recommended dosage for adults ranges from 40 mg/day to 1 mg/kg/day of prednisone given orally; for more severe cases, 1 g of methylprednisolone per day should be used. Treatment with corticosteroids induces a rapid reduction in the eosinophil count in most patients; however, the tapering of corticosteroids usually needs to be prolonged over months (median maintenance dose, 10 mg/day). Some authors have suggested that the response to corticosteroids can be predicted based on the disease subtype, with myeloid and lymphocytic HES variants having worse response compared to HES, EGPA, and HES with single-organ involvement. […] The persistence of blood eosinophilia despite the administration of corticosteroids suggests that treatment needs to be intensified with the addition of a second medication. Hydroxyurea may be used as a first-line therapy in combination with corticosteroids, or as monotherapy in non-respondents. Hydroxyurea effectively controls leukocytes and eosinophils count, but there is no evidence of an influence on the natural history of HES. A second-line option for patients who fail to respond to, or do not tolerate, corticosteroids and hydroxyurea is interferon-α (IFN-α). IFN-α can produce hematologic or cytogenetic remission, as well as reverse organ injury. In patients with aggressive disease, bone marrow/peripheral blood allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted with variable results. Leukapheresis can elicit transient reductions in high leukocyte and eosinophil counts but is ineffective in the long term. Anti-platelet and anticoagulant agents may be useful for preventing thromboembolism; however, a standard approach regulating their use as primary prevention in patients with HES is currently lacking. Other immunosuppressive drugs such as cyclosporine, azathioprine, and methotrexate can be used in patients with HES to control the disease and as steroid-sparing drugs.

• #27 Hypereosinophilic Syndrome Medication: Corticosteroids, Antineoplastic Agents, Immunomodulators, Interleukin Inhibitors

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

  May be instituted in patients whose condition fails or is only partially responsive to hydroxyurea. A response is often observed within 1-3 d. Marrow suppression is less common than with hydroxyurea, but occurrence of neurologic toxicity may limit treatment and closely resemble the neurologic symptoms of hypereosinophilic syndrome. […] Primary alkylating agent used in cases in which prednisone fails and in those patients who cannot tolerate hydroxyurea or vincristine. A reasonable alternative for long-term treatment. Bone marrow suppression may be a problem. […] Etoposide is a glycosidic derivative of podophyllotoxin that exerts a cytotoxic effect by stabilizing the normally transient covalent intermediates formed between the DNA substrate and topoisomerase II. The drug leads to single-stranded and double-stranded DNA breaks that arrest cellular proliferation in the late S or early G2 phase of cell cycle.

• #28 Hypereosinophilic Syndromes – Apfed

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

  Interferon alpha (IFNa) is used for a variety of diseases including infections (like hepatitis) and malignancies (like certain types of leukemia). IFNa has been shown to be effective in HES by suppressing the symptoms related to the disease. Toxicity, however, is a major obstacle to the use of this therapy. […] Cyclosporine is a potent medication that suppresses the immune system and it is used primarily to prevent organ rejection in people who have had organ transplants. In some patients with HES there might be evidence that the immune cells have a role in supporting the diseases existence (so-called T cells) and cyclosporine may have a role as therapy in such cases. […] Anti-neoplastic agents (chemotherapy) provide an alternative approach to therapy of advanced cases of HES. These are chemotherapeutic agents that may control the disease.

• #29 List of 5 Hypereosinophilic Syndrome Medications Compared

  https://www.drugs.com/condition/hypereosinophilic-syndrome.html

  Medications for Hypereosinophilic Syndrome […] The medications listed below are related to or used in the treatment of this condition. […] Nucala to treat Hypereosinophilic Syndrome […] mepolizumab to treat Hypereosinophilic Syndrome […] Gleevec, Imatinib

• #30 FDA approves Nucala as the first and only biologic treatment for Hypereosinophilic Syndrome (HES) | GSK

  https://www.gsk.com/en-gb/media/press-releases/fda-approves-nucala-as-the-first-and-only-biologic-treatment-for-hypereosinophilic-syndrome-hes/

  GlaxoSmithKline plc (GSK) today announced the US Food and Drug Administration (FDA) has approved Nucala (mepolizumab) for the treatment of adult and paediatric patients aged 12 years and older with Hypereosinophilic Syndrome (HES) for six months without an identifiable non-haematologic secondary cause. The approval makes Nucala the first and only targeted biologic treatment to be approved for patients with this eosinophil-driven disease in the US. […] For the first time, we now have a biologic treatment option to offer appropriate patients with this complex disease. […] Nucala is currently used as an add-on maintenance therapy for severe eosinophilic asthma and for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA), and is being investigated in several other eosinophil-driven diseases. […] In a clinical trial in patients with Hypereosinophilic Syndrome, no additional adverse reactions were identified to those reported in the severe asthma trials.

• #31 Hypereosinophilic Syndromes – Apfed

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

  Gleevec (Imatinib Mesylate) is a tyrosine kinase inhibitor. […] For patients who are refractory to conventional therapies, use of monoclonal antibody therapy (medications that selectively bind to specific proteins) should be considered. A drug currently available is mepolizumab, which targets interleukin-5, a cytokine in blood that is recognized as a very important protein that governs eosinophil growth. Mepolizumab blocks interleukin-5 and eliminates a cytokine from blood that provides signal for eosinophil growth.

• #32

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

  Mepolizumab, a monoclonal anti-IL-5 antibody, has recently been shown to enable CS-tapering while maintaining disease control and eosinophil depletion in a high proportion of patients with HES, with little if any side effects compared to placebo. […] Once full-blown peripheral T-cell lymphoma has developed in patients initially diagnosed with L-HES, eradication of malignant T cells is not easily achieved using classical chemotherapeutic regimens. […] In conclusion, improved understanding of HES pathogenesis in patient subgroups has modified management of this chronic and often debilitating disorder.

• #33 Low-dose anti-IL 5 treatment in idiopathic hypereosinophilic syndrome: towards a precision medicine approach for remission maintenance | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02918-9

  Mepolizumab at the dose of 300 mg/4 weeks has been recently approved as an add-on therapy for patients with uncontrolled hypereosinophilic syndrome (HES) without any identifiable non-hematologic secondary cause. […] We investigated the efficacy and safety of mepolizumab 100 mg in idiopathic HES (I-HES) patients as a steroid sparing strategy for disease remission maintenance by assessing clinical conditions, blood eosinophil count (BEC) and adverse events at baseline and at 3612 months follow-up. […] Although larger studies are needed, our report firstly describes that in a well-defined population, diagnosed with I-HES and in disease remission, low dose mepolizumab is a safe and effective steroid-sparing option for remission maintenance. […] It suggests that a personalized treatment dose might be explored according to the disease classification and activity at the time of biologic treatment start.

• #34 Low-dose anti-IL 5 treatment in idiopathic hypereosinophilic syndrome: towards a precision medicine approach for remission maintenance | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02918-9

  Mepolizumab at the dose of 300 mg/4 weeks has been recently approved as an add-on therapy for patients with uncontrolled hypereosinophilic syndrome (HES) without any identifiable non-hematologic secondary cause. […] We investigated the efficacy and safety of mepolizumab 100 mg in idiopathic HES (I-HES) patients as a steroid sparing strategy for disease remission maintenance by assessing clinical conditions, blood eosinophil count (BEC) and adverse events at baseline and at 3612 months follow-up. […] Although larger studies are needed, our report firstly describes that in a well-defined population, diagnosed with I-HES and in disease remission, low dose mepolizumab is a safe and effective steroid-sparing option for remission maintenance. […] It suggests that a personalized treatment dose might be explored according to the disease classification and activity at the time of biologic treatment start.

• #35 Low-dose anti-IL 5 treatment in idiopathic hypereosinophilic syndrome: towards a precision medicine approach for remission maintenance | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02918-9

  In our study, mepolizumab 100 mg in patients with I-HES was initiated prior to the approval of 300 mg/monthly for that indication by the regulatory authorities, that represents the main reason for the off-label use of the drug in our population. […] Our study suggests that low dose mepolizumab might be considered a safe and effective steroid-sparing option in the remission maintenance of I-HES patients. […] In addition, our findings support the idea that a tailored targeted-treatment dose could be part of a personalized approach to HES patients.

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

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

  Patients with the FIP1L1/PDGFRA-associated fusion gene (or similar fusion genes involving PDGFA/B) are usually treated with imatinib and, particularly if heart damage is suspected, corticosteroids as well. […] Patients without the FIP1L1/PDGFRA-associated fusion gene, even if asymptomatic, are often given one dose of prednisone 60 mg (or 1 mg/kg) orally to determine corticosteroid responsiveness (ie, a decrease in the eosinophil count). […] Mepolizumab, a fully humanized monoclonal IgG antibody that inhibits binding of IL-5 to its receptor, may be used for the treatment of idiopathic hypereosinophilia. […] Reslizumab (anti-IL-5), benralizumab (anti-IL-5 receptor), and dupilumab (anti-Il-4 receptor) are other biologics that have been used in hypereosinophilic syndrome. […] Supportive medication therapy and surgery may be required for cardiac manifestations (eg, infiltrative cardiomyopathy, valvular lesions, heart failure).

• #37 Hypereosinophilic Dermatitis: Treatment with Dupilumab | BTT

  https://www.dovepress.com/hypereosinophilic-dermatitis-successful-treatment-with-dupilumab-peer-reviewed-fulltext-article-BTT

  Hypereosinophilic dermatitis (HED) is a subtype of hypereosinophilic syndrome. […] At present, in addition to HED with FIP1L1-PDGFRA fusion gene positive, whose treatment is tyrosine kinase inhibitor, other types of HED first-line treatment are oral glucocorticoids, supplemented by antihistamines and immunosuppressants. Dupilumab is a human monoclonal antibody, which inhibits the IL-4 and IL-13 signaling by binding to the IL-4R- and IL-13R–1 subunits of the receptor. […] Dupilumab was initiated with the recommended dose. There was a significant improvement of the skin lesions after 2 weeks from the first injection of dupilumab. The lesions had completely resolved after 8 weeks. […] Dupilumab has good effect and safety in the treatment of moderate to severe AD. […] Dupilumab, a biologic for atopic dermatitis, has shown promising results in HED.

• #38 Hypereosinophilic syndrome presenting as coagulopathy | Allergy, Asthma & Clinical Immunology | Full Text

  https://aacijournal.biomedcentral.com/articles/10.1186/s13223-022-00666-2

  Shortly after discharge, benralizumab was started at 30 mg subcutaneously every 4 weeks for three doses then every 8 weeks. […] After remaining asymptomatic for 10 months while on benralizumab, anticoagulation therapy was discontinued. […] While corticosteroid therapy is first line for idiopathic HES, newer biologic medications have shown promise in reducing eosinophilia and clinical symptoms of HES. […] Benralizumab is an anti-IL-5 receptor agent approved for severe eosinophilic asthma. […] Given evidence that eosinophils play a direct role in thrombosis, targeting eosinophils may prevent further thrombotic complications. […] Rapid diagnosis of HES and utilization of steroid-sparing agents such as anti-IL-5 therapies could help prevent further end-organ damage, treat an underlying mechanism for associated coagulopathy, and avoid long-term side effects of corticosteroid use.

• #39 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  For patients with FIP1L1/PDGFRA mutation, imatinib is the drug of choice. The response rate in these cases approaches 100% in various studies. […] Mepolizumab, a humanized monoclonal antibody specific for interleukin-5 (IL-5), is the first treatment shown to reduce disease flares in patients with FIP1L1/PDGFRA-negative hypereosinophilic syndrome. […] For hypereosinophilic syndrome that is refractory to the usual treatments, chemotherapeutic agents that have been used with some success include chlorambucil, etoposide, vincristine, and cladribine and cytarabine. […] Alternatively, in refractory cases, particularly those resistant to imatinib therapy, hematopoietic stem cell transplantation (HSCT) has been shown to reverse the organ dysfunction. […] Leukapheresis is indicated as an emergency therapy in hypereosinophilic syndrome to control symptoms due to hyperleukocytosis.

• #40 Hypereosinophilic Syndrome Medication: Corticosteroids, Antineoplastic Agents, Immunomodulators, Interleukin Inhibitors

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

  May be instituted in patients whose condition fails or is only partially responsive to hydroxyurea. A response is often observed within 1-3 d. Marrow suppression is less common than with hydroxyurea, but occurrence of neurologic toxicity may limit treatment and closely resemble the neurologic symptoms of hypereosinophilic syndrome. […] Primary alkylating agent used in cases in which prednisone fails and in those patients who cannot tolerate hydroxyurea or vincristine. A reasonable alternative for long-term treatment. Bone marrow suppression may be a problem. […] Etoposide is a glycosidic derivative of podophyllotoxin that exerts a cytotoxic effect by stabilizing the normally transient covalent intermediates formed between the DNA substrate and topoisomerase II. The drug leads to single-stranded and double-stranded DNA breaks that arrest cellular proliferation in the late S or early G2 phase of cell cycle.

• #41 Hypereosinophilic Syndrome Medication: Corticosteroids, Antineoplastic Agents, Immunomodulators, Interleukin Inhibitors

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

  May be instituted in patients whose condition fails or is only partially responsive to hydroxyurea. A response is often observed within 1-3 d. Marrow suppression is less common than with hydroxyurea, but occurrence of neurologic toxicity may limit treatment and closely resemble the neurologic symptoms of hypereosinophilic syndrome. […] Primary alkylating agent used in cases in which prednisone fails and in those patients who cannot tolerate hydroxyurea or vincristine. A reasonable alternative for long-term treatment. Bone marrow suppression may be a problem. […] Etoposide is a glycosidic derivative of podophyllotoxin that exerts a cytotoxic effect by stabilizing the normally transient covalent intermediates formed between the DNA substrate and topoisomerase II. The drug leads to single-stranded and double-stranded DNA breaks that arrest cellular proliferation in the late S or early G2 phase of cell cycle.

• #42 Hypereosinophilic Syndrome Medication: Corticosteroids, Antineoplastic Agents, Immunomodulators, Interleukin Inhibitors

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

  May be instituted in patients whose condition fails or is only partially responsive to hydroxyurea. A response is often observed within 1-3 d. Marrow suppression is less common than with hydroxyurea, but occurrence of neurologic toxicity may limit treatment and closely resemble the neurologic symptoms of hypereosinophilic syndrome. […] Primary alkylating agent used in cases in which prednisone fails and in those patients who cannot tolerate hydroxyurea or vincristine. A reasonable alternative for long-term treatment. Bone marrow suppression may be a problem. […] Etoposide is a glycosidic derivative of podophyllotoxin that exerts a cytotoxic effect by stabilizing the normally transient covalent intermediates formed between the DNA substrate and topoisomerase II. The drug leads to single-stranded and double-stranded DNA breaks that arrest cellular proliferation in the late S or early G2 phase of cell cycle.

• #43 Hypereosinophilic Syndrome Medication: Corticosteroids, Antineoplastic Agents, Immunomodulators, Interleukin Inhibitors

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

  May be instituted in patients whose condition fails or is only partially responsive to hydroxyurea. A response is often observed within 1-3 d. Marrow suppression is less common than with hydroxyurea, but occurrence of neurologic toxicity may limit treatment and closely resemble the neurologic symptoms of hypereosinophilic syndrome. […] Primary alkylating agent used in cases in which prednisone fails and in those patients who cannot tolerate hydroxyurea or vincristine. A reasonable alternative for long-term treatment. Bone marrow suppression may be a problem. […] Etoposide is a glycosidic derivative of podophyllotoxin that exerts a cytotoxic effect by stabilizing the normally transient covalent intermediates formed between the DNA substrate and topoisomerase II. The drug leads to single-stranded and double-stranded DNA breaks that arrest cellular proliferation in the late S or early G2 phase of cell cycle.

• #44 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  Due to the rapidity and reliability of its effect, a 5-day course of prednisone (1 mg/kg/d or 60 mg/d) is the initial treatment of choice for all FIP1L1/PGDFRA negative patients. […] Almost 70% of patients with hypereosinophilic syndrome respond well to steroid therapy, especially those who present with urticaria and high IgE levels. […] Imatinib mesylate (Gleevec) is the drug of choice for hypereosinophilic syndrome with FIP1L1/PDGFRA. […] In patients with hypereosinophilic syndrome with FIP1L1/PDGFRA, imatinib induces clinical hematologic and molecular remission in the majority of cases. […] Interferon alpha is a second-line drug of choice for patients whose condition does not respond to glucocorticoids. Hydroxyurea has also demonstrated efficacy for steroid-refractory cases. […] Alemtuzumab, an anti-CD52 monoclonal antibody, has been shown to control symptoms as well as eosinophilia in patients with refractory hypereosinophilic syndrome. […] Periodically observe patients with hypereosinophilic syndrome to confirm that the eosinophilia is controlled and that no evidence of new or worsening organ involvement occurs.

• #45 Hypereosinophilic Syndromes – Apfed

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

  Interferon alpha (IFNa) is used for a variety of diseases including infections (like hepatitis) and malignancies (like certain types of leukemia). IFNa has been shown to be effective in HES by suppressing the symptoms related to the disease. Toxicity, however, is a major obstacle to the use of this therapy. […] Cyclosporine is a potent medication that suppresses the immune system and it is used primarily to prevent organ rejection in people who have had organ transplants. In some patients with HES there might be evidence that the immune cells have a role in supporting the diseases existence (so-called T cells) and cyclosporine may have a role as therapy in such cases. […] Anti-neoplastic agents (chemotherapy) provide an alternative approach to therapy of advanced cases of HES. These are chemotherapeutic agents that may control the disease.

• #46 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

  Corticosteroids are the first-line option for patients with idiopathic HES (HES). The recommended dosage for adults ranges from 40 mg/day to 1 mg/kg/day of prednisone given orally; for more severe cases, 1 g of methylprednisolone per day should be used. Treatment with corticosteroids induces a rapid reduction in the eosinophil count in most patients; however, the tapering of corticosteroids usually needs to be prolonged over months (median maintenance dose, 10 mg/day). Some authors have suggested that the response to corticosteroids can be predicted based on the disease subtype, with myeloid and lymphocytic HES variants having worse response compared to HES, EGPA, and HES with single-organ involvement. […] The persistence of blood eosinophilia despite the administration of corticosteroids suggests that treatment needs to be intensified with the addition of a second medication. Hydroxyurea may be used as a first-line therapy in combination with corticosteroids, or as monotherapy in non-respondents. Hydroxyurea effectively controls leukocytes and eosinophils count, but there is no evidence of an influence on the natural history of HES. A second-line option for patients who fail to respond to, or do not tolerate, corticosteroids and hydroxyurea is interferon-α (IFN-α). IFN-α can produce hematologic or cytogenetic remission, as well as reverse organ injury. In patients with aggressive disease, bone marrow/peripheral blood allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted with variable results. Leukapheresis can elicit transient reductions in high leukocyte and eosinophil counts but is ineffective in the long term. Anti-platelet and anticoagulant agents may be useful for preventing thromboembolism; however, a standard approach regulating their use as primary prevention in patients with HES is currently lacking. Other immunosuppressive drugs such as cyclosporine, azathioprine, and methotrexate can be used in patients with HES to control the disease and as steroid-sparing drugs.

• #47 Hypereosinophilic syndrome – Wikipedia

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

  It has been demonstrated that immunomodulatory drugs, such as interferon-alpha, cyclosporine, and intravenous immunoglobulin, that influence Th2 cytokine production and T cell proliferation can be therapeutically effective in HES. […] The U.S. Food and Drug Administration (FDA) has approved imatinib mesylate, a tyrosine kinase inhibitor, as the first treatment for HES. […] An option for patients who have not responded to conventional treatment regimens is a stem cell transplant.

• #48 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

  Imatinib is an effective treatment in patients with HES caused by a PDGFRA/B-rearranged eosinophilic neoplasm. Patients with HE and the rearranged clonal marker FIP1L1-PDGFRA are included in the category “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion” and usually present an excellent response to imatinib. Most patients achieve molecular remission with a 100 mg/day dose, while the maintenance dose may vary between 100 and 400 mg/day. For patients with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion with eosinophilia and the PDGFRB rearrangement, the imatinib recommended dose is 400 mg/day for inducing remission and 100 mg/day for maintenance. Imatinib’s safety profile in eosinophilic disorders aligns with the good tolerability seen in CML. A few cases of cardiogenic shock associated with imatinib have, however, been described. The FGFR1 inhibitor pemigatinib has recently been approved by the FDA for the treatment of patients with myeloid/lymphoid neoplasms with FGFR1 rearrangement. The JAK1/JAK2 inhibitor ruxolitinib is currently under investigation in HES and primary eosinophilic disorders. Additional tyrosine kinase inhibitor therapies targeting JAK2 and FLT3 have shown promising results. Lastly, dasatinib, an experimental anti-cancer drug designed to block the function of BCR-ABL, has been recently evaluated in several myeloproliferative disorders, including HES.

• #49 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

  Imatinib is an effective treatment in patients with HES caused by a PDGFRA/B-rearranged eosinophilic neoplasm. Patients with HE and the rearranged clonal marker FIP1L1-PDGFRA are included in the category “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion” and usually present an excellent response to imatinib. Most patients achieve molecular remission with a 100 mg/day dose, while the maintenance dose may vary between 100 and 400 mg/day. For patients with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion with eosinophilia and the PDGFRB rearrangement, the imatinib recommended dose is 400 mg/day for inducing remission and 100 mg/day for maintenance. Imatinib’s safety profile in eosinophilic disorders aligns with the good tolerability seen in CML. A few cases of cardiogenic shock associated with imatinib have, however, been described. The FGFR1 inhibitor pemigatinib has recently been approved by the FDA for the treatment of patients with myeloid/lymphoid neoplasms with FGFR1 rearrangement. The JAK1/JAK2 inhibitor ruxolitinib is currently under investigation in HES and primary eosinophilic disorders. Additional tyrosine kinase inhibitor therapies targeting JAK2 and FLT3 have shown promising results. Lastly, dasatinib, an experimental anti-cancer drug designed to block the function of BCR-ABL, has been recently evaluated in several myeloproliferative disorders, including HES.

• #50 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

  Imatinib is an effective treatment in patients with HES caused by a PDGFRA/B-rearranged eosinophilic neoplasm. Patients with HE and the rearranged clonal marker FIP1L1-PDGFRA are included in the category “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion” and usually present an excellent response to imatinib. Most patients achieve molecular remission with a 100 mg/day dose, while the maintenance dose may vary between 100 and 400 mg/day. For patients with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion with eosinophilia and the PDGFRB rearrangement, the imatinib recommended dose is 400 mg/day for inducing remission and 100 mg/day for maintenance. Imatinib’s safety profile in eosinophilic disorders aligns with the good tolerability seen in CML. A few cases of cardiogenic shock associated with imatinib have, however, been described. The FGFR1 inhibitor pemigatinib has recently been approved by the FDA for the treatment of patients with myeloid/lymphoid neoplasms with FGFR1 rearrangement. The JAK1/JAK2 inhibitor ruxolitinib is currently under investigation in HES and primary eosinophilic disorders. Additional tyrosine kinase inhibitor therapies targeting JAK2 and FLT3 have shown promising results. Lastly, dasatinib, an experimental anti-cancer drug designed to block the function of BCR-ABL, has been recently evaluated in several myeloproliferative disorders, including HES.

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

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

  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. […] If you have no symptoms and your eosinophil count is low enough, you might require no treatment other than close monitoring for any changes related to HES. […] Systemic corticosteroids, such as prednisone, are the first line treatment. Other treatment options include: Hydroxyurea (Droxia, Hydrea, Siklos), Imatinib (Gleevec), Vincristine. […] Because HES can increase your risk of blood clots, you might also be prescribed blood-thinning medications such as warfarin (Coumadin). […] If nothing else has worked, your doctor might suggest a stem cell or bone marrow transplant.

• #52 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

  Corticosteroids are the first-line option for patients with idiopathic HES (HES). The recommended dosage for adults ranges from 40 mg/day to 1 mg/kg/day of prednisone given orally; for more severe cases, 1 g of methylprednisolone per day should be used. Treatment with corticosteroids induces a rapid reduction in the eosinophil count in most patients; however, the tapering of corticosteroids usually needs to be prolonged over months (median maintenance dose, 10 mg/day). Some authors have suggested that the response to corticosteroids can be predicted based on the disease subtype, with myeloid and lymphocytic HES variants having worse response compared to HES, EGPA, and HES with single-organ involvement. […] The persistence of blood eosinophilia despite the administration of corticosteroids suggests that treatment needs to be intensified with the addition of a second medication. Hydroxyurea may be used as a first-line therapy in combination with corticosteroids, or as monotherapy in non-respondents. Hydroxyurea effectively controls leukocytes and eosinophils count, but there is no evidence of an influence on the natural history of HES. A second-line option for patients who fail to respond to, or do not tolerate, corticosteroids and hydroxyurea is interferon-α (IFN-α). IFN-α can produce hematologic or cytogenetic remission, as well as reverse organ injury. In patients with aggressive disease, bone marrow/peripheral blood allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted with variable results. Leukapheresis can elicit transient reductions in high leukocyte and eosinophil counts but is ineffective in the long term. Anti-platelet and anticoagulant agents may be useful for preventing thromboembolism; however, a standard approach regulating their use as primary prevention in patients with HES is currently lacking. Other immunosuppressive drugs such as cyclosporine, azathioprine, and methotrexate can be used in patients with HES to control the disease and as steroid-sparing drugs.

• #53 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

  Overall, while the natural history of HES associated with MLN-TK neoplasms presenting the PDGFRA or PDGFRB rearrangements has dramatically improved with the introduction of tyrosine kinase inhibitors (imatinib, in particular), neoplasms with FGFR1, JAK2, and FLT3 fusions and ETV6::ABL1 show variable sensitivity to the newer tyrosine kinase inhibitors. In the majority of these cases, allogeneic HSCT may be the only available cure.

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

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

  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. […] If you have no symptoms and your eosinophil count is low enough, you might require no treatment other than close monitoring for any changes related to HES. […] Systemic corticosteroids, such as prednisone, are the first line treatment. Other treatment options include: Hydroxyurea (Droxia, Hydrea, Siklos), Imatinib (Gleevec), Vincristine. […] Because HES can increase your risk of blood clots, you might also be prescribed blood-thinning medications such as warfarin (Coumadin). […] If nothing else has worked, your doctor might suggest a stem cell or bone marrow transplant.

• #55 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

  Corticosteroids are the first-line option for patients with idiopathic HES (HES). The recommended dosage for adults ranges from 40 mg/day to 1 mg/kg/day of prednisone given orally; for more severe cases, 1 g of methylprednisolone per day should be used. Treatment with corticosteroids induces a rapid reduction in the eosinophil count in most patients; however, the tapering of corticosteroids usually needs to be prolonged over months (median maintenance dose, 10 mg/day). Some authors have suggested that the response to corticosteroids can be predicted based on the disease subtype, with myeloid and lymphocytic HES variants having worse response compared to HES, EGPA, and HES with single-organ involvement. […] The persistence of blood eosinophilia despite the administration of corticosteroids suggests that treatment needs to be intensified with the addition of a second medication. Hydroxyurea may be used as a first-line therapy in combination with corticosteroids, or as monotherapy in non-respondents. Hydroxyurea effectively controls leukocytes and eosinophils count, but there is no evidence of an influence on the natural history of HES. A second-line option for patients who fail to respond to, or do not tolerate, corticosteroids and hydroxyurea is interferon-α (IFN-α). IFN-α can produce hematologic or cytogenetic remission, as well as reverse organ injury. In patients with aggressive disease, bone marrow/peripheral blood allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted with variable results. Leukapheresis can elicit transient reductions in high leukocyte and eosinophil counts but is ineffective in the long term. Anti-platelet and anticoagulant agents may be useful for preventing thromboembolism; however, a standard approach regulating their use as primary prevention in patients with HES is currently lacking. Other immunosuppressive drugs such as cyclosporine, azathioprine, and methotrexate can be used in patients with HES to control the disease and as steroid-sparing drugs.

• #56 Hypereosinophilic syndrome presenting as coagulopathy | Allergy, Asthma & Clinical Immunology | Full Text

  https://aacijournal.biomedcentral.com/articles/10.1186/s13223-022-00666-2

  Shortly after discharge, benralizumab was started at 30 mg subcutaneously every 4 weeks for three doses then every 8 weeks. […] After remaining asymptomatic for 10 months while on benralizumab, anticoagulation therapy was discontinued. […] While corticosteroid therapy is first line for idiopathic HES, newer biologic medications have shown promise in reducing eosinophilia and clinical symptoms of HES. […] Benralizumab is an anti-IL-5 receptor agent approved for severe eosinophilic asthma. […] Given evidence that eosinophils play a direct role in thrombosis, targeting eosinophils may prevent further thrombotic complications. […] Rapid diagnosis of HES and utilization of steroid-sparing agents such as anti-IL-5 therapies could help prevent further end-organ damage, treat an underlying mechanism for associated coagulopathy, and avoid long-term side effects of corticosteroid use.

• #57 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

  Currently, the use of empiric antiparasitic treatments (e.g., flubendazole or albendazole) is still a topic of debate. The authors sustaining this approach underline the variable sensitivity of the parasite serology and of the available tests for the detection of parasites in stool, together with the favorable safety and low cost of these drugs, which often avoid the need for second-line investigations. In addition, in patients with HES and a history of potential exposure to Strongyloides stercoralis, ivermectin (an anti-helminthic agent) at the dose of 200 µg/kg on day 1 followed by a second dose on day 2 or day 15 in the case of the diagnostic confirmation of strongyloidiasis should be added to corticosteroid therapy to prevent the severe reaction elicited by this pathogen in the patients receiving corticosteroids.

• #58 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

  Currently, the use of empiric antiparasitic treatments (e.g., flubendazole or albendazole) is still a topic of debate. The authors sustaining this approach underline the variable sensitivity of the parasite serology and of the available tests for the detection of parasites in stool, together with the favorable safety and low cost of these drugs, which often avoid the need for second-line investigations. In addition, in patients with HES and a history of potential exposure to Strongyloides stercoralis, ivermectin (an anti-helminthic agent) at the dose of 200 µg/kg on day 1 followed by a second dose on day 2 or day 15 in the case of the diagnostic confirmation of strongyloidiasis should be added to corticosteroid therapy to prevent the severe reaction elicited by this pathogen in the patients receiving corticosteroids.

• #59 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  For patients with FIP1L1/PDGFRA mutation, imatinib is the drug of choice. The response rate in these cases approaches 100% in various studies. […] Mepolizumab, a humanized monoclonal antibody specific for interleukin-5 (IL-5), is the first treatment shown to reduce disease flares in patients with FIP1L1/PDGFRA-negative hypereosinophilic syndrome. […] For hypereosinophilic syndrome that is refractory to the usual treatments, chemotherapeutic agents that have been used with some success include chlorambucil, etoposide, vincristine, and cladribine and cytarabine. […] Alternatively, in refractory cases, particularly those resistant to imatinib therapy, hematopoietic stem cell transplantation (HSCT) has been shown to reverse the organ dysfunction. […] Leukapheresis is indicated as an emergency therapy in hypereosinophilic syndrome to control symptoms due to hyperleukocytosis.

• #60 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

  Corticosteroids are the first-line option for patients with idiopathic HES (HES). The recommended dosage for adults ranges from 40 mg/day to 1 mg/kg/day of prednisone given orally; for more severe cases, 1 g of methylprednisolone per day should be used. Treatment with corticosteroids induces a rapid reduction in the eosinophil count in most patients; however, the tapering of corticosteroids usually needs to be prolonged over months (median maintenance dose, 10 mg/day). Some authors have suggested that the response to corticosteroids can be predicted based on the disease subtype, with myeloid and lymphocytic HES variants having worse response compared to HES, EGPA, and HES with single-organ involvement. […] The persistence of blood eosinophilia despite the administration of corticosteroids suggests that treatment needs to be intensified with the addition of a second medication. Hydroxyurea may be used as a first-line therapy in combination with corticosteroids, or as monotherapy in non-respondents. Hydroxyurea effectively controls leukocytes and eosinophils count, but there is no evidence of an influence on the natural history of HES. A second-line option for patients who fail to respond to, or do not tolerate, corticosteroids and hydroxyurea is interferon-α (IFN-α). IFN-α can produce hematologic or cytogenetic remission, as well as reverse organ injury. In patients with aggressive disease, bone marrow/peripheral blood allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted with variable results. Leukapheresis can elicit transient reductions in high leukocyte and eosinophil counts but is ineffective in the long term. Anti-platelet and anticoagulant agents may be useful for preventing thromboembolism; however, a standard approach regulating their use as primary prevention in patients with HES is currently lacking. Other immunosuppressive drugs such as cyclosporine, azathioprine, and methotrexate can be used in patients with HES to control the disease and as steroid-sparing drugs.

• #61 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  Due to the rapidity and reliability of its effect, a 5-day course of prednisone (1 mg/kg/d or 60 mg/d) is the initial treatment of choice for all FIP1L1/PGDFRA negative patients. […] Almost 70% of patients with hypereosinophilic syndrome respond well to steroid therapy, especially those who present with urticaria and high IgE levels. […] Imatinib mesylate (Gleevec) is the drug of choice for hypereosinophilic syndrome with FIP1L1/PDGFRA. […] In patients with hypereosinophilic syndrome with FIP1L1/PDGFRA, imatinib induces clinical hematologic and molecular remission in the majority of cases. […] Interferon alpha is a second-line drug of choice for patients whose condition does not respond to glucocorticoids. Hydroxyurea has also demonstrated efficacy for steroid-refractory cases. […] Alemtuzumab, an anti-CD52 monoclonal antibody, has been shown to control symptoms as well as eosinophilia in patients with refractory hypereosinophilic syndrome. […] Periodically observe patients with hypereosinophilic syndrome to confirm that the eosinophilia is controlled and that no evidence of new or worsening organ involvement occurs.

• #62 Hypereosinophilic syndrome – wikidoc

  https://www.wikidoc.org/index.php/Hypereosinophilic_syndrome

  Once diagnosed and successfully treated, patients with hypereosinophilic syndrome are followed-up periodically every 6 or 12 months depending on the clinical progression. […] Follow-up testing includes the following tests: complete blood count, biochemical profile (liver enzymes, creatine kinase, renal function, and troponin), electrocardiogram, and tissue biopsies.

• #63 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  Whether and how to treat symptomatic hypereosinophilic syndrome depends on the clinical presentation, laboratory findings, and mutational analysis. Currently, treating asymptomatic patients with hypereosinophilic syndrome is not recommended, as treatment itself is not without risks. Such patients are closely monitored with serum troponin measurements every 3-6 months, and echocardiography and pulmonary function tests every 6-12 months. […] In contrast, cases of hypereosinophilic syndrome with myeloproliferative features, particularly those with FIP1L1/PDGFRA mutation, should be treated aggressively. These patients carry a worse prognosis without treatment. […] In all patients without FIP1L1/PDGFRA mutation, glucocorticoids are the first-line therapy. About one third of these cases do not respond to steroids. In such patients, interferon alpha and hydroxyurea are the recommended second-line drugs. For third-line therapy, high-dose (400 mg/d) imatinib is the treatment of choice.

• #64 Hypereosinophilic syndromes: Treatment – UpToDate

  https://www.uptodate.com/contents/hypereosinophilic-syndromes-treatment

  Hypereosinophilic syndromes: Treatment […] The urgency of treatment and choice of therapy is based on the patient’s presentation, as well as laboratory findings and the results of mutational analysis. […] The overall goals of therapy are reduction of the absolute eosinophil count (AEC), amelioration of signs and symptoms, and prevention of disease progression. […] The urgency with which patients are treated depends on the severity of hypereosinophilia (HE) and the presence of signs and symptoms of the disease.

• #65

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

  Mepolizumab, a monoclonal anti-IL-5 antibody, has recently been shown to enable CS-tapering while maintaining disease control and eosinophil depletion in a high proportion of patients with HES, with little if any side effects compared to placebo. […] Once full-blown peripheral T-cell lymphoma has developed in patients initially diagnosed with L-HES, eradication of malignant T cells is not easily achieved using classical chemotherapeutic regimens. […] In conclusion, improved understanding of HES pathogenesis in patient subgroups has modified management of this chronic and often debilitating disorder.

• #66 Steroid-Sparing Therapy for Hypereosinophilic Syndromelogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b

  https://www.jwatch.org/na46738/2018/05/16/steroid-sparing-therapy-hypereosinophilic-syndrome

  Dexpramipexole safely decreased the minimum effective steroid dose by ≥50% in a subset of patients in a small, proof-of-concept study. […] To examine whether dexpramipexole might play a steroid-sparing therapeutic role in the hypereosinophilic syndrome, investigators conducted a nonrandomized trial in 10 patients with glucocorticoid-responsive disease. […] This goal was achieved in four patients, three of whom had a decrease in absolute eosinophil count to ≤10/μL within 8 weeks of dexpramipexole initiation and were able to discontinue glucocorticoids. […] Patients with various subtypes of hypereosinophilic syndrome benefitted from dexpramipexole in this proof-of-concept study. […] Based on this favorable preliminary study, a multicenter, randomized, placebo-controlled phase III trial of dexpramipexole for hypereosinophilic syndrome is being planned.

• #67 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

  Corticosteroids are the first-line option for patients with idiopathic HES (HES). The recommended dosage for adults ranges from 40 mg/day to 1 mg/kg/day of prednisone given orally; for more severe cases, 1 g of methylprednisolone per day should be used. Treatment with corticosteroids induces a rapid reduction in the eosinophil count in most patients; however, the tapering of corticosteroids usually needs to be prolonged over months (median maintenance dose, 10 mg/day). Some authors have suggested that the response to corticosteroids can be predicted based on the disease subtype, with myeloid and lymphocytic HES variants having worse response compared to HES, EGPA, and HES with single-organ involvement. […] The persistence of blood eosinophilia despite the administration of corticosteroids suggests that treatment needs to be intensified with the addition of a second medication. Hydroxyurea may be used as a first-line therapy in combination with corticosteroids, or as monotherapy in non-respondents. Hydroxyurea effectively controls leukocytes and eosinophils count, but there is no evidence of an influence on the natural history of HES. A second-line option for patients who fail to respond to, or do not tolerate, corticosteroids and hydroxyurea is interferon-α (IFN-α). IFN-α can produce hematologic or cytogenetic remission, as well as reverse organ injury. In patients with aggressive disease, bone marrow/peripheral blood allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted with variable results. Leukapheresis can elicit transient reductions in high leukocyte and eosinophil counts but is ineffective in the long term. Anti-platelet and anticoagulant agents may be useful for preventing thromboembolism; however, a standard approach regulating their use as primary prevention in patients with HES is currently lacking. Other immunosuppressive drugs such as cyclosporine, azathioprine, and methotrexate can be used in patients with HES to control the disease and as steroid-sparing drugs.

• #68 Steroid-Sparing Therapy for Hypereosinophilic Syndromelogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b

  https://www.jwatch.org/na46738/2018/05/16/steroid-sparing-therapy-hypereosinophilic-syndrome

  Dexpramipexole safely decreased the minimum effective steroid dose by ≥50% in a subset of patients in a small, proof-of-concept study. […] To examine whether dexpramipexole might play a steroid-sparing therapeutic role in the hypereosinophilic syndrome, investigators conducted a nonrandomized trial in 10 patients with glucocorticoid-responsive disease. […] This goal was achieved in four patients, three of whom had a decrease in absolute eosinophil count to ≤10/μL within 8 weeks of dexpramipexole initiation and were able to discontinue glucocorticoids. […] Patients with various subtypes of hypereosinophilic syndrome benefitted from dexpramipexole in this proof-of-concept study. […] Based on this favorable preliminary study, a multicenter, randomized, placebo-controlled phase III trial of dexpramipexole for hypereosinophilic syndrome is being planned.

• #69 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  Whether and how to treat symptomatic hypereosinophilic syndrome depends on the clinical presentation, laboratory findings, and mutational analysis. Currently, treating asymptomatic patients with hypereosinophilic syndrome is not recommended, as treatment itself is not without risks. Such patients are closely monitored with serum troponin measurements every 3-6 months, and echocardiography and pulmonary function tests every 6-12 months. […] In contrast, cases of hypereosinophilic syndrome with myeloproliferative features, particularly those with FIP1L1/PDGFRA mutation, should be treated aggressively. These patients carry a worse prognosis without treatment. […] In all patients without FIP1L1/PDGFRA mutation, glucocorticoids are the first-line therapy. About one third of these cases do not respond to steroids. In such patients, interferon alpha and hydroxyurea are the recommended second-line drugs. For third-line therapy, high-dose (400 mg/d) imatinib is the treatment of choice.

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

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

  Treatment options for HES are summarized in Table I. Systemic corticosteroids are the mainstay and the first-line treatment for most patients, except for those with M-HES. In patients who have M-HES with F/P mutation, imatinib, a monoclonal antibody against tyrosine kinase, is the first-line therapy. Patients with M-HES who do not have a F/P mutation still respond to imatinib and that should be the first-line treatment for them as well. […] In M-HES with positive F/P mutation, imatinib mesylate, a tyrosine kinase inhibitor, has dramatically decreased the morbidity and mortality and is the first line and treatment of choice regardless of severity of disease. This therapy should also be considered in M-HES without F/P mutation. […] In L-HES, corticosteroids are the first-line treatment if patients are symptomatic. Most patients respond to 30-60mg prednisone. Once symptomatic improvement has been achieved and eosinophil count has normalized, slow tapering to 10mg over the course of months should be attempted. Monoclonal antibody against IL-5 has been successfully used in research trials for this type.

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

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

  Treatment options for HES are summarized in Table I. Systemic corticosteroids are the mainstay and the first-line treatment for most patients, except for those with M-HES. In patients who have M-HES with F/P mutation, imatinib, a monoclonal antibody against tyrosine kinase, is the first-line therapy. Patients with M-HES who do not have a F/P mutation still respond to imatinib and that should be the first-line treatment for them as well. […] In M-HES with positive F/P mutation, imatinib mesylate, a tyrosine kinase inhibitor, has dramatically decreased the morbidity and mortality and is the first line and treatment of choice regardless of severity of disease. This therapy should also be considered in M-HES without F/P mutation. […] In L-HES, corticosteroids are the first-line treatment if patients are symptomatic. Most patients respond to 30-60mg prednisone. Once symptomatic improvement has been achieved and eosinophil count has normalized, slow tapering to 10mg over the course of months should be attempted. Monoclonal antibody against IL-5 has been successfully used in research trials for this type.

• #72 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

  Corticosteroids are the first-line option for patients with idiopathic HES (HES). The recommended dosage for adults ranges from 40 mg/day to 1 mg/kg/day of prednisone given orally; for more severe cases, 1 g of methylprednisolone per day should be used. Treatment with corticosteroids induces a rapid reduction in the eosinophil count in most patients; however, the tapering of corticosteroids usually needs to be prolonged over months (median maintenance dose, 10 mg/day). Some authors have suggested that the response to corticosteroids can be predicted based on the disease subtype, with myeloid and lymphocytic HES variants having worse response compared to HES, EGPA, and HES with single-organ involvement. […] The persistence of blood eosinophilia despite the administration of corticosteroids suggests that treatment needs to be intensified with the addition of a second medication. Hydroxyurea may be used as a first-line therapy in combination with corticosteroids, or as monotherapy in non-respondents. Hydroxyurea effectively controls leukocytes and eosinophils count, but there is no evidence of an influence on the natural history of HES. A second-line option for patients who fail to respond to, or do not tolerate, corticosteroids and hydroxyurea is interferon-α (IFN-α). IFN-α can produce hematologic or cytogenetic remission, as well as reverse organ injury. In patients with aggressive disease, bone marrow/peripheral blood allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted with variable results. Leukapheresis can elicit transient reductions in high leukocyte and eosinophil counts but is ineffective in the long term. Anti-platelet and anticoagulant agents may be useful for preventing thromboembolism; however, a standard approach regulating their use as primary prevention in patients with HES is currently lacking. Other immunosuppressive drugs such as cyclosporine, azathioprine, and methotrexate can be used in patients with HES to control the disease and as steroid-sparing drugs.

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

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

  Treatment options for HES are summarized in Table I. Systemic corticosteroids are the mainstay and the first-line treatment for most patients, except for those with M-HES. In patients who have M-HES with F/P mutation, imatinib, a monoclonal antibody against tyrosine kinase, is the first-line therapy. Patients with M-HES who do not have a F/P mutation still respond to imatinib and that should be the first-line treatment for them as well. […] In M-HES with positive F/P mutation, imatinib mesylate, a tyrosine kinase inhibitor, has dramatically decreased the morbidity and mortality and is the first line and treatment of choice regardless of severity of disease. This therapy should also be considered in M-HES without F/P mutation. […] In L-HES, corticosteroids are the first-line treatment if patients are symptomatic. Most patients respond to 30-60mg prednisone. Once symptomatic improvement has been achieved and eosinophil count has normalized, slow tapering to 10mg over the course of months should be attempted. Monoclonal antibody against IL-5 has been successfully used in research trials for this type.

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

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

  Treatment options for HES are summarized in Table I. Systemic corticosteroids are the mainstay and the first-line treatment for most patients, except for those with M-HES. In patients who have M-HES with F/P mutation, imatinib, a monoclonal antibody against tyrosine kinase, is the first-line therapy. Patients with M-HES who do not have a F/P mutation still respond to imatinib and that should be the first-line treatment for them as well. […] In M-HES with positive F/P mutation, imatinib mesylate, a tyrosine kinase inhibitor, has dramatically decreased the morbidity and mortality and is the first line and treatment of choice regardless of severity of disease. This therapy should also be considered in M-HES without F/P mutation. […] In L-HES, corticosteroids are the first-line treatment if patients are symptomatic. Most patients respond to 30-60mg prednisone. Once symptomatic improvement has been achieved and eosinophil count has normalized, slow tapering to 10mg over the course of months should be attempted. Monoclonal antibody against IL-5 has been successfully used in research trials for this type.

• #75

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

  Mepolizumab, a monoclonal anti-IL-5 antibody, has recently been shown to enable CS-tapering while maintaining disease control and eosinophil depletion in a high proportion of patients with HES, with little if any side effects compared to placebo. […] Once full-blown peripheral T-cell lymphoma has developed in patients initially diagnosed with L-HES, eradication of malignant T cells is not easily achieved using classical chemotherapeutic regimens. […] In conclusion, improved understanding of HES pathogenesis in patient subgroups has modified management of this chronic and often debilitating disorder.

• #76 How I treat hypereosinophilic syndromes

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4551360/

  If the eosinophil count and symptoms do not improve after 1 to 2 days of high-dose corticosteroid therapy, a second agent should be added to rapidly lower the eosinophil count. […] The most commonly used second-line therapies are hydroxyurea (1-2 g orally daily) and interferon- (1-3 mU subcutaneously daily), each of which is effective in 30% of patients. […] Corticosteroids remain the mainstay of therapy for idiopathic HES. […] High-dose corticosteroids are often effective in the short-term reduction of eosinophilia and clinical manifestations in patients with PDGFR-negative M-HES and are useful in the initial management of such patients. […] Patients with documented rearrangements or mutations involving PDGFRA should be treated with imatinib mesylate (100-400 mg by mouth daily). […] A number of agents that target eosinophils are currently in clinical development for the treatment of eosinophilic disorders. […] Mepolizumab is currently available only on clinical protocols for patients with life-threatening HES refractory to standard therapies (as in the case presented) or with EGPA.

• #77 Orphanet: Hypereosinophilic syndrome

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

  Therapeutic management should be adjusted to disease severity and eventual detection of pathogenic variants. For F/P+ patients, imatinib has undisputedly become first line therapy. For others, corticosteroids are generally administered initially, followed by agents such as hydroxycarbamide, interferon-alpha, and imatinib, for corticosteroid-resistant cases, as well as for corticosteroid-sparing purposes. Recent data suggest that mepolizumab, an anti-IL-5 antibody that is currently available only in the setting of clinical trials or on a compassionate use basis for severe treatment-refractory disease, is an effective corticosteroid-sparing agent for F/P-negative patients.

• #78 Low-dose anti-IL 5 treatment in idiopathic hypereosinophilic syndrome: towards a precision medicine approach for remission maintenance | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02918-9

  Mepolizumab at the dose of 300 mg/4 weeks has been recently approved as an add-on therapy for patients with uncontrolled hypereosinophilic syndrome (HES) without any identifiable non-hematologic secondary cause. […] We investigated the efficacy and safety of mepolizumab 100 mg in idiopathic HES (I-HES) patients as a steroid sparing strategy for disease remission maintenance by assessing clinical conditions, blood eosinophil count (BEC) and adverse events at baseline and at 3612 months follow-up. […] Although larger studies are needed, our report firstly describes that in a well-defined population, diagnosed with I-HES and in disease remission, low dose mepolizumab is a safe and effective steroid-sparing option for remission maintenance. […] It suggests that a personalized treatment dose might be explored according to the disease classification and activity at the time of biologic treatment start.

• #79 Low-dose anti-IL 5 treatment in idiopathic hypereosinophilic syndrome: towards a precision medicine approach for remission maintenance | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02918-9

  In our study, mepolizumab 100 mg in patients with I-HES was initiated prior to the approval of 300 mg/monthly for that indication by the regulatory authorities, that represents the main reason for the off-label use of the drug in our population. […] Our study suggests that low dose mepolizumab might be considered a safe and effective steroid-sparing option in the remission maintenance of I-HES patients. […] In addition, our findings support the idea that a tailored targeted-treatment dose could be part of a personalized approach to HES patients.

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

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

  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. […] If you have no symptoms and your eosinophil count is low enough, you might require no treatment other than close monitoring for any changes related to HES. […] Systemic corticosteroids, such as prednisone, are the first line treatment. Other treatment options include: Hydroxyurea (Droxia, Hydrea, Siklos), Imatinib (Gleevec), Vincristine. […] Because HES can increase your risk of blood clots, you might also be prescribed blood-thinning medications such as warfarin (Coumadin). […] If nothing else has worked, your doctor might suggest a stem cell or bone marrow transplant.

• #81 Hypereosinophilic Syndrome Treatment & Management: Approach Considerations, Surgical Care, Glucocorticoids

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

  Whether and how to treat symptomatic hypereosinophilic syndrome depends on the clinical presentation, laboratory findings, and mutational analysis. Currently, treating asymptomatic patients with hypereosinophilic syndrome is not recommended, as treatment itself is not without risks. Such patients are closely monitored with serum troponin measurements every 3-6 months, and echocardiography and pulmonary function tests every 6-12 months. […] In contrast, cases of hypereosinophilic syndrome with myeloproliferative features, particularly those with FIP1L1/PDGFRA mutation, should be treated aggressively. These patients carry a worse prognosis without treatment. […] In all patients without FIP1L1/PDGFRA mutation, glucocorticoids are the first-line therapy. About one third of these cases do not respond to steroids. In such patients, interferon alpha and hydroxyurea are the recommended second-line drugs. For third-line therapy, high-dose (400 mg/d) imatinib is the treatment of choice.

• #82

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

  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. […] Higher doses of imatinib are generally required to observe a response in the absence of FIP1L1-PDGFRA, so the initial dose should be 400 mg. […] The other major mechanism involved in HES pathogenesis described so far is polyclonal eosinophil expansion in response to IL-5 in the setting of a primitive T-cell disorder. […] Corticosteroids (CS) remain first-line therapy for patients with L-HES, and absolute numbers of CD3-CD4 T cells have been shown to decrease in some patients treated with CS alone. […] Second-line and/or CS-sparing therapeutic options for patients with L-HES include interferon-alpha (IFN-), which has mostly been reported successful for treating HES patients with features of myeloproliferative disease, and possibly alemtuzumab.

• #83 Hypereosinophilic syndrome presenting as coagulopathy | Allergy, Asthma & Clinical Immunology | Full Text

  https://aacijournal.biomedcentral.com/articles/10.1186/s13223-022-00666-2

  A 33-year-old previously healthy male with no history of atopic disease presented with abdominal pain, hematochezia, peripheral eosinophilia as high as 10,000 eos/L, right and left portal vein, mesenteric, and splenic vein thrombi with ischemic colitis resulting in hemicolectomy and small bowel resection. […] His eosinophilia was successfully treated with high-dose oral corticosteroids (OCS) and subsequently transitioned to anti-IL-5-receptor therapy with benralizumab. […] Corticosteroid-sparing agents, such as benralizumab show promise for successfully treating these patients. […] Treatment of HES patients with thrombi have previously include corticosteroids, anticoagulants, and antiplatelet agents, which have many risks when used long term. […] Recently, anti-interleukin-5 (anti-IL-5) and anti-IL-5-receptor antibody therapies have shown promise as steroid-sparing treatment for HES.

• #84 Hypereosinophilic syndrome presenting as coagulopathy | Allergy, Asthma & Clinical Immunology | Full Text

  https://aacijournal.biomedcentral.com/articles/10.1186/s13223-022-00666-2

  Shortly after discharge, benralizumab was started at 30 mg subcutaneously every 4 weeks for three doses then every 8 weeks. […] After remaining asymptomatic for 10 months while on benralizumab, anticoagulation therapy was discontinued. […] While corticosteroid therapy is first line for idiopathic HES, newer biologic medications have shown promise in reducing eosinophilia and clinical symptoms of HES. […] Benralizumab is an anti-IL-5 receptor agent approved for severe eosinophilic asthma. […] Given evidence that eosinophils play a direct role in thrombosis, targeting eosinophils may prevent further thrombotic complications. […] Rapid diagnosis of HES and utilization of steroid-sparing agents such as anti-IL-5 therapies could help prevent further end-organ damage, treat an underlying mechanism for associated coagulopathy, and avoid long-term side effects of corticosteroid use.

• #85 A Hypereosinophilic Syndrome Presenting as Eosinophilic Colitis

  https://www.e-ce.org/journal/view.php?doi=10.5946/ce.2012.45.4.444

  Hypereosinophilic syndrome (HES) has three defining features: marked hypereosinophilia for at least 6 months, no confirmed etiology for the eosinophilia, and eosinophilia-related symptoms or organ dysfunction. […] Although hypereosinophilia was present for 3 months, this patient needed to be treated with eosinophil-lowering therapy for severe hematochezia. After systemic corticosteroid therapy, symptoms caused by organ involvement were dramatically improved. […] Early initiation of therapy may be recommended in HES patients with symptoms. […] Oral corticosteroid therapy (prednisolone, 60 mg/day) was started for HES with severe symptoms caused by multiple organ involvement. […] Three days later, symptoms such as abdominal pain, bloody diarrhea, and cough were improved dramatically. […] The primary goal of treatment is to reduce the eosinophilia to 1,500/mm3 and to prevent further damage to major organs.

• #86 A Hypereosinophilic Syndrome Presenting as Eosinophilic Colitis

  https://www.e-ce.org/journal/view.php?doi=10.5946/ce.2012.45.4.444

  Surgery should be reserved for patients with significant bleeding, perforation, and GI obstruction and for patients who are refractory to medical treatment. […] Because HES can involve multiple organs and have fatal course, we think eosinophil-lowering therapy should be started as soon as possible to prevent aggressive disease progression and organ dysfunction.

• #87 A Hypereosinophilic Syndrome Presenting as Eosinophilic Colitis

  https://www.e-ce.org/journal/view.php?doi=10.5946/ce.2012.45.4.444

  Surgery should be reserved for patients with significant bleeding, perforation, and GI obstruction and for patients who are refractory to medical treatment. […] Because HES can involve multiple organs and have fatal course, we think eosinophil-lowering therapy should be started as soon as possible to prevent aggressive disease progression and organ dysfunction.

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