Hypereosinophilic Syndrome

Disease Overview

Summary

Hypereosinophilic syndrome (HES) is a group of disorders characterized by abnormally high levels of immune cells called eosinophils in the blood (eosinophilia) and organ damage as a result of these elevated levels. Eosinophils are white blood cells that are normally produced in response to allergies, asthma, or infections. In HES, elevated levels disrupt the normal functions of organs or body systems, most commonly the skin, lungs, heart, gastrointestinal tract and nervous system. People with HES may have no symptoms or may have severe symptoms, like heart failure or stroke.

HES can be inherited or can be caused by certain bone marrow disorders, infections, or inflammatory disorders. Treatment options depend on the underlying cause and disease severity, but the overall goal of treatment is to reduce the level of eosinophils, treat any associated symptoms and prevent disease progression.

Introduction

HES was first identified as a specific syndrome in 1968. The definition for its diagnosis was established in 1975. This definition includes an eosinophil blood count greater than 1,500 cells/uL for more than 6 months, in the presence of no other identifiable cause for high blood levels of eosinophils and evidence that eosinophils are affecting organs.¹ Normal eosinophil counts are less than 500 cells/uL.²

The Working Conference on Eosinophil Disorders and Syndromes introduced revised terminology for eosinophilic syndromes to improve clarity in diagnosis and classification. HES is currently categorized into five clinically relevant variants.

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Synonyms

• hypereosinophilic disease
• HES

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Subdivisions

• primary or clonal or neoplastic HES (HESN) includes myeloid and lymphocytic variants
• secondary or reactive HES (HER)
• familial or hereditary HES (HESFA)
• HE of undetermined significance (HEUS) which replaces the term idiopathic HES (IHES)
• organ-restricted HES or overlap HES

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Signs & Symptoms

Eosinophils in HES cause signs and symptoms by infiltrating organs and blood vessels and releasing substances that damage tissues and disrupt normal organ function.³ Signs and symptoms of HES often appear gradually, although in some people, symptoms can be sudden and severe. Furthermore, blood eosinophil levels do not always predict the severity of symptoms — for instance, people with severe symptoms may have only mildly elevated eosinophil levels in the blood.⁴ Some people with HES may be asymptomatic, with their only sign of the disease being high blood levels of eosinophils (eosinophilia). Any organ can be affected by HES. Symptoms vary based on which organs are targeted by eosinophils; in many people, multiple organ systems are affected.⁵ General symptoms of HES include fatigue, fever, muscle pain and night sweats.⁴ The most commonly affected organ and body systems are the skin, lungs, gastrointestinal tract, heart and nervous system.³

The skin is most commonly affected by HES. Skin symptoms include eczema, hives, swelling beneath the skin (angioedema), skin thickening, skin reddening and welt formation after scratching the skin (dermatographism).⁶

When the lungs are affected, symptoms include shortness of breath, coughing and wheezing. Cells may accumulate in lung areas that are normally filled with air, blood clots may form in the lungs and fluid may collect between layers of the lung (pleural effusions).

Gastrointestinal symptoms of HES include weight loss, difficulty swallowing, abdominal pain, nausea, vomiting, diarrhea and ulcers in the lining of the mouth and other areas of the gastrointestinal tract.⁴ Eosinophils can collect and cause inflammation in the esophagus, stomach, small intestines, large intestine, liver and gallbladder. HES can also lead to blockages in the veins that drain the liver, a condition known as Budd-Chiari syndrome.⁶

HES can damage heart tissue, causing heart cells to die, clots to form, heart tissues to harden, and heart chambers to malfunction. Cardiac involvement can lead to heart failure and death and may include signs and symptoms of a cough, shortness of breath (including when lying down), chest pain, palpitations, heart murmurs, heart enlargement and heart failure.^3,4,6

Neurological effects of HES include numbness or tingling in the hands or feet (neuropathy), muscle pain, muscle weakness, confusion, discoordination, memory loss and ministrokes or stroke.⁴ Symptoms of neuropathy usually affect both sides of the body in people with HES.³ People with HES may also have joint pain.³

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Causes

HES is grouped into different types based on the underlying cause or presentation of the illness: primary HES, secondary HES, familial HES, idiopathic HES and organ-restricted HES.⁶ Primary HES is further divided into a myeloid subtype and lymphocytic subtype. The myeloid subtype occurs because of gene changes (variants) that lead to bone marrow abnormalities and subsequent overproduction of eosinophils. These variants are new (de novo) in the affected person and are not inherited. Variants in many different genes are associated with myeloid HES including FIP1L1, PDGFRA, PDGFRB, FGFR1, STAT5B, JAK1, JAK2, ABL1 and FTL3.^3,6 Variants in PDGFRA in particular, are more likely to cause cardiac symptoms in people with HES.³

Chronic eosinophilic leukemia is also classified as a type of myeloid HES.⁶ The lymphocytic HES subtype is caused by abnormal T cells (a type of immune cell) that inappropriately release substances that encourage excess eosinophil production.⁶ One of these substances is interleukin-5, which is a target of some treatments for HES.⁸

Secondary HES, also known as reactive HES, is the most common type of HES.⁴ It occurs in response to an infection, inflammatory process, or a drug. Infections with parasitic worms can cause secondary HES.⁴ Inflammatory diseases associated with secondary HES include inflammatory bowel disease, Addison disease, scleroderma, polyarteritis nodosa, sarcoidosis and allergic bronchopulmonary aspergillosis.^3,4,6 Secondary HES can also occur in response to certain cancers, including colon cancer and T-cell lymphoma and leukemias.^3,9 Drugs that can induce secondary HES include anticonvulsants, certain penicillins (antibiotics) and allopurinol.¹⁰

A hereditary type of HES, called familial HES, can also occur. This type is diagnosed when there is a known family history of long-term eosinophilia, and no other cause of HES is identified.⁶ Some cases of familial HES can be traced back to specific genes or conditions associated with immunodeficiencies that run in families. Familial HES is usually identified in children but may not become noticeable until adulthood.⁴

Another type of HES, idiopathic HES, now known as HE of undermined significance or HEUS, is diagnosed when HES cannot be attributed to any known cause. Some people with HES who are initially diagnosed with idiopathic HES are later found to have an identifiable cause for HES and, as such, are diagnosed with another type of HES.³

Finally, organ-restricted HES is a specific type of HES in which only one organ is damaged by high eosinophil levels. The organ-restricted HES is often referred to as overlap HES because the person meets the blood criteria for HES but primarily has only one organ system affected such as eosinophilic gastritis. People with this type of HES usually do not have the systemic manifestations associated with HES. The other types of HES typically affect multiple organs and body systems. Additionally, organ-restricted HES may or may not be associated with high blood levels of eosinophilia, and when it is associated with high blood levels, elevations are not as extreme as with the other forms of HES. Causes of organ-restricted HES can be the same as the causes of primary and secondary forms of HES.⁴

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Affected populations

HES is more likely to occur in males than females by a ratio of 9:1.³ Although HES can occur at any age, it is more likely to occur in people between 20 and 50 years old.³ HES does not occur more often in any single race.² It has an estimated prevalence of 0.315 to 6.3 per 100,000 people.⁶

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Disorders with Similar Symptoms

Other disorders can cause high blood levels of eosinophils or inflammation of organs, but without eosinophils playing a major role in inflammation.

A condition known as episodic angioedema and eosinophilia (EAE), or Gleich syndrome, is related to high blood counts of eosinophils and skin symptoms that may overlap with HES, but other organs are not usually affected like with HES. Skin symptoms and other symptoms like fever that occur with EAE tend to occur in episodes, usually every few weeks, and symptoms last over several days.¹¹

Eosinophilic granulomatosis with polyangiitis (EGPA), or Churg-Strauss syndrome, is associated with eosinophilia, asthma symptoms and lung disease. EGPA affects the blood vessels and is considered a type of vasculitis. In some people, EGPA may be associated with certain antibodies (ANCA) that are not present in people with HES. Antibody testing and a biopsy that demonstrates vasculitis may be able to differentiate EGPA from HES.¹²

Eosinophilia myalgia syndrome includes a high blood count of eosinophils and muscle pain (myalgia). It can be considered a type of secondary HES, but, unlike other forms of HES, it occurs specifically in response to ingestion of impurities in the dietary supplement L-tryptophan.¹³

IgG4-related disease is an autoimmune disease associated with blood eosinophilia; however, organ damage in this condition is attributed to immune cells that release IgG4 antibodies, which can cause scarring and hardening of the affected tissues.¹⁴

Systemic mastocytosis, a blood disorder, can be associated with eosinophilia. Symptoms may overlap with HES, including fatigue, skin symptoms and heart palpitations. However, in systemic mastocytosis tissue damage occurs because of an overabundance of mast cells, which are immune cells that release histamine. Systemic mastocytosis can also be differentiated from HES based on the identification of KIT D816V gene variants.⁶  In addition, mastocytosis can be present as a secondary manifestation of myeloid HES.

Two forms of leukemia that may have overlapping symptoms with HES but do not meet the diagnostic criteria of HES are acute eosinophilic leukemia and chronic myeloid leukemia.⁶ Acute eosinophilic leukemia, which is associated with an increased number of immature eosinophils circulating in the body, is distinguished from HES based on results from a bone marrow biopsy. The bone marrow of people with acute eosinophilic leukemia has a higher percentage of immature blood cells than the bone marrow of people with HES.⁶ Eosinophilia may also occur with chronic myeloid leukemia, but symptoms from eosinophilia are less likely with this disease. Chronic myeloid leukemia can be distinguished from HES based on associated gene variants.⁶

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Diagnosis

HES has a specific set of criteria for diagnosis, including: ⁶

• Detection of eosinophilia greater than 1,500 cells/uL on at least two blood tests taken at least one month apart
• Detection of more than 20% of eosinophils on bone marrow biopsy
• Observation of an extensive collection of eosinophils or their proteins on tissue biopsy
• Identification of organ or tissue damage
• Exclusion of other disorders that could explain organ damage.

HES is defined as severe when the absolute eosinophil count is greater than 50,000 cells/uL, the nervous system or lungs are involved in the disease process, or life-threatening symptoms like heart failure or blood clots are present.¹⁵

The diagnostic process involves confirming persistent eosinophilia through laboratory tests (complete blood count and a blood smear) and detecting organ damage by eosinophils.¹⁶ Other tests performed will depend on the person’s signs and symptoms. Even people with eosinophilia who are asymptomatic should have further testing to determine the cause of their eosinophilia.³ Part of the diagnostic workup is classifying the type of HES a person may have. Further laboratory tests may help diagnose a reactive, or secondary, form of HES, which may be easier to treat than other forms of HES.⁶ For instance, if something in a person’s medical history suggests a parasitic infection, a stool test can be ordered to detect parasite eggs. Other laboratory tests relevant to HES include comprehensive blood chemistries, liver enzyme testing, renal function tests, creatine kinase testing and troponin measurements.³

Once the more obvious causes of secondary HES are ruled out, people can have more extensive testing to determine the type of HES they may have. Imaging can help detect organ involvement or help rule out other disorders that could be causing similar symptoms to HES. For instance, people with respiratory or abdominal symptoms may have an X-ray or CT scan of the affected organs to look for findings typical of lung or gastrointestinal disease associated with HES. Heart (cardiac) involvement in HES can be fatal. People with suspected HES should have an electrocardiogram and an echocardiogram.⁴ An MRI of the heart may be necessary if these tests reveal abnormal findings.⁴ Biopsy of affected organs, including skin lesions (when present), can confirm that eosinophils are causing organ damage.⁴ An electrocardiogram (ECG) measures the heart’s electrical activity to assess rhythm and rate, while an echocardiogram (echo) uses ultrasound to create images of the heart’s structure and function.

When primary forms of HES are suspected, certain blood tests can be useful. When myeloid HES is suspected, useful blood tests are serum tryptase and vitamin B12 levels.⁴ Blood testing known as quantitative immunoglobulin testing is useful for suspected lymphocytic HES because it measures levels of antibodies in the blood that are increased with this form of HES.⁴ Flow cytometry testing, a laboratory technique used to analyze and characterize cells in a sample, can also be done for suspected cases of lymphocytic HES to detect abnormal T-cell populations.^17,18 Additionally, people with suspected lymphocytic HES may need to have testing for a viral infection known as mononucleosis, which is a cause of lymphocytic HES in some people.^6,17

Bone marrow biopsy can also help with detecting primary forms of HES and ruling out similar disorders. Additionally, bone marrow biopsy can aid in the diagnosis of secondary HES in response to lymphoma or another cancer that affects the bone marrow.⁴ Bone marrow biopsy is a medical procedure that involves removing a small sample of bone marrow, the spongy tissue inside the bone, for examination.

Molecular genetic testing of a blood or tissue sample can also be used to look for abnormal T-cell markers associated with lymphocytic HES or gene variants associated with myeloid HES.⁶ Genetic testing may be needed to distinguish some cases of primary HES from systemic mastocytosis with eosinophilia and may be useful in some cases of familial HES.³

Blood or bone marrow samples can be tested for known cancer-causing gene variants using next generation sequencing.  Genetic testing in HES includes the following categories:

Targeted fusion / rearrangement testing

• To detect FIP1L1–PDGFRA, a fusion gene formed by a deletion at chromosome 4q12 that causes the FIP1L1 gene to fuse with the PDGFRA gene (a specific genetic marker associated with certain blood disorders such as myeloid HES and chronic eosinophilic leukemia) the tests used are RT-PCR or FISH. Myeloid HES responds very well to the drug imatinib.
• To detect PDGFRB gene rearrangements leading to myeloid neoplasm with eosinophilia, the test types used are FISH or next-generation sequencing (NGS) and a fusion panel focused on chromosome 5. This type is treatable with imatinib.
• To detect FGFR1 gene rearrangements (that can cause a type of cancer involving both the bone marrow and lymph nodes known as 8p11 myeloid/lymphoid neoplasm and which often progresses to acute leukemia or lymphoma) the test types used are FISH or NGS. This type is not treatable with imatinib and requires different, often more aggressive treatment.
• To detect BCR–ABL1, a fusion gene formed when pieces of chromosomes 9 and 22 break off and trade places (the changed chromosome 22 is called the Philadelphia chromosome) and is found in most people with chronic myelogenous leukemia and in some people with acute lymphoblastic leukemia, the tests used are RT-PCR or FISH. The goal is to rule out chronic myeloid leukemia (CML), a condition that can also cause high eosinophil levels. If positive, treatment with tyrosine kinase inhibitors (TKIs) is appropriate.
• To detect JAK2 V617F (a variant in the JAK2 gene common in many bone marrow disorders) the test used is PCR. Its presence may guide treatment with JAK inhibitors.
• To detect KIT D816V (the D816V variant of the KIT gene causes the protein to become permanently activated, leading to the uncontrolled proliferation and survival of mast cells, and is commonly present in systemic mastocytosis) the test used is PCR to rule out systemic mastocytosis. Its presence guides use of targeted therapies like midostaurin or avapritinib.

Broad myeloid mutation panel (NGS)

• Genes tested: TET2, DNMT3A, ASXL1, RUNX1, JAK2, CALR, MPL, CBL, CSF3R, KRAS, NRAS, SETBP1, EZH2, IDH1, IDH2, TP53, SF3B1, SRSF2, U2AF1, ZRSR2, STAT3, STAT5B and others using a next-generation sequencing (NGS) test with a comprehensive leukemia panel
  • Identifies clonal (cancer-like) mutations in bone marrow cells that suggest the eosinophilia is due to a blood cancer, not a reactive cause
  • Helps confirm diagnoses like chronic eosinophilic leukemia, not otherwise specified (CELNOS) and may reveal variants that can be directly targeted with newer therapies

Cytogenetic analysis

• The test used is conventional chromosomal analysis (karyotyping).
  • Detects large-scale structural or numerical changes in chromosomes that might be missed by gene panels
  • Helps clarify diagnosis, assess prognosis and determine how aggressive the disease may be

Lymphocytic variant testing

• The tests used are flow cytometry to analyze T-cell surface markers and PCR to look for clonal rearrangement in T-cell receptor (TCR) genes (purpose is to  identify lymphocytic variant HES (L-HES), caused by abnormal T-cells that produce high levels of interleukin-5 (IL-5) — a protein that drives eosinophil production).
  • Confirms L-HES and supports treatment with immunosuppressive or biologic therapies such as steroids or mepolizumab

Overview of genetic tests

• RT-PCR (reverse transcriptase-polymerase chain reaction) identifies specific gene fusions or variants by converting RNA into DNA and amplifying it so that even very small amounts of abnormal genetic material can be detected.
• FISH (fluorescence in situ hybridization) uses fluorescent probes to highlight specific genes or chromosome regions under a microscope, helping to detect missing pieces, extra copies, or rearrangements of genetic material.
• PCR (polymerase chain reaction) is a technique that amplifies small sections of DNA, making it easier to identify known gene variants such as those seen in certain blood disorders.
• Karyotyping, also known as conventional cytogenetics, examines the overall structure and number of chromosomes in cells to identify large-scale genetic changes that might not be picked up by other tests.
• Next-Generation Sequencing (NGS) allows for the analysis of many genes at the same time and can detect both common and rare gene variants associated with blood cancers or clonal conditions.
• Flow cytometry, a method that analyzes the size, shape and surface markers of cells in a blood or bone marrow sample, is particularly useful for identifying abnormal T-cells that may be driving eosinophil overproduction.
• T-cell receptor (TCR) gene rearrangement testing, performed using PCR, looks for identical (clonal) T-cell populations by analyzing the structure of genes involved in T-cell function and can confirm the presence of a lymphocytic variant of HES.

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Standard Therapies

Treatment of HES varies based on the type of HES a person has and its severity. The goal of treatment is to lower eosinophil levels, prevent organ damage from progressing and reduce symptoms.⁶ People with familial HES who do not have symptoms may not need treatment, only to be carefully followed up.¹⁵ These people should be regularly observed for any signs or symptoms of heart or lung involvement.³ Secondary HES due to parasitic infections can be treated with antiparasitic medications. Secondary HES due to drug use can be treated by stopping the drug use.

Myeloid HES, especially when associated with FIP1L1/PDGFRA gene variants, should be treated more intensively. The preferred treatment for these patients is imatinib.¹⁶ Imatinib is a type of drug called a tyrosine kinase inhibitor and is typically used to treat leukemia. People with myeloid HES typically get better with imatinib, but lifelong therapy may be needed.³ Higher doses of imatinib may be helpful for idiopathic HES.³ Glucocorticoids may be combined with imatinib for people with myeloid HES who have heart problems.¹⁵

For most other cases of HES (that are not associated with FIP1L1/PDGFRA gene variants), glucocorticoids alone are the first preferred treatment to try. Glucocorticoids are steroids with anti-inflammatory effects.

Severe HES is treated with intravenous administration of the glucocorticoids prednisone or methylprednisolone. The eosinophil count in these patients typically lowers fast within a day.¹⁵

Other patients with less severe HES who are given oral glucocorticoids typically improve with the treatment as well, within a month. However, patients may need to maintain treatment with glucocorticoids long-term to keep symptoms under control.⁶

If people with non-myeloid HES do not improve with glucocorticoid treatment, then imatinib may be recommended as well.⁶

The medication hydroxyurea can also be used as a second option in people who do not improve with glucocorticoids alone. Hydroxyurea can be used instead of glucocorticoids, or it can be taken alongside a lower dose of glucocorticoids. Patients may have a better response to the two medications combined rather than to hydroxyurea alone.⁶

Mepolizumab can also be used by patients with HES on glucocorticoids to help reduce their dose of glucocorticoids (and decrease their side effects).^6,19 Mepolizumab is a monoclonal antibody treatment that targets interleukin-5 (a protein released by immune cells). Mepolizumab is approved by the U.S. Food and Drug Administration (FDA) for the treatment of HES that is not related to a secondary cause.³

The FDA has approved Fasenra (benralizumab) for patients aged 12 years and older with hypereosinophilic syndrome (HES) who do not have an identifiable non-blood-related cause of the disease. Fasenra was already approved for severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis. ²¹

The approval was based on results from the Phase III NATRON trial. In the study, patients who received Fasenra as a 30-mg injection under the skin every four weeks had a 65% lower risk of HES worsening or experiencing a disease flare over 24 weeks compared with those receiving placebo in addition to standard treatment. Fasenra also reduced the number of flares, lowered annual flare rates, and improved patient-reported fatigue.

People with lymphocytic HES may be treated with interferon alfa combined with glucocorticoids. Interferon alfa is a medication that reduces the body’s natural production of a protein called interleukin-5 by acting on certain white blood cells (CD4 T cells).^6,15

Additionally, patients with HES that have heart problems may need procedures like a heart valve replacement, removal of the endocardium (endocardiectomy) due to fibrosis, or removal of blood clots (thrombectomy). In some people, clots can cause the spleen to become enlarged, and the spleen may need to be removed (splenectomy).³ For HES patients with blood clots, blood thinners are usually prescribed.¹⁵

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Clinical Trials and Studies

Other monoclonal antibodies similar to mepolizumab are being studied for the treatment of HES, including reslizumab, dupilumab and a long-acting form of mepolizumab, depemokimab.¹⁵

Other medications are under investigation for patients with HES who do not respond to glucocorticoids. JAK inhibitors tofacitinib and ruxolitnib have shown promise in case reports for treating lymphocytic and idiopathic forms of HES.¹⁵

For cases of HES that do not respond to the typical treatments, chemotherapy with chlorambucil, etoposide, vincristine and cladribine with cytarabine may be tried.³

A treatment known as hematopoietic stem cell transplantation may also be used as a treatment of last resort in resistant cases (especially primary HES forms), but it is considered risky.^3,22 Hematopoietic stem cell transplantation or bone marrow transplant, is a medical procedure where healthy hematopoietic stem cells (HSCs) are transplanted into a patient to replace their damaged or diseased bone marrow, the spongy tissue inside the bones where blood cells are made.

Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website:https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact: http://www.centerwatch.com/

For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/

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References

1. Hardy WR, Anderson RE. The hypereosinophilic syndromes. Ann Intern Med. 1968 Jun. 68(6):1220-9.
2. Rothenberg ME. Eosinophilia. N Engl J Med. 1998;338(22):1592-1600. doi:10.1056/NEJM199805283382206
3. Rothschild BM, Sacher RA, Herrin VE, Files JC, Zhou Y. Hypereosinophilic syndrome. Medscape. Updated July 30, 2024. https://emedicine.medscape.com/article/202030-overview Accessed October 15, 2025.
4. Roufosse F, Klion AD, Weller PF. Hypereosinophilic syndromes: clinical manifestations, diagnosis, and classification. UpToDate. Updated August 4, 2025. https://www.uptodate.com/contents/hypereosinophilic-syndromes-clinical-manifestations-diagnosis-and-classification Accessed October 13, 2025.
5. Groh M, Rohmer J, Etienne N, et al. French guidelines for the etiological workup of eosinophilia and the management of hypereosinophilic syndromes. Orphanet J Rare Dis. 2023; 18:100.
6. Mikhail ES, Ghatol A. Hypereosinophilic Syndrome. [Updated 2024 Jan 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK599558/ Accessed October 15, 2025.
7. Groh M, Fenwarth L, Labro M, et al. Involvement of the JAK-STAT pathway in the molecular landscape of tyrosine kinase fusion-negative hypereosinophilic syndromes: A nationwide CEREO study. Am J Hematol. 2024; 99:1108.
8. Shomali W, Gotlib J. World Health Organization-defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022; 97:129.
9. Helbig G, Wieczorkiewicz A, Dziaczkowska-Suszek J, Majewski M, Kyrcz-Krzemien S. T-cell abnormalities are present at high frequencies in patients with hypereosinophilic syndrome. Haematologica 2009 Sep. 94(9):1236-41.
10. Roufosse F, Weller PF. Practical approach to the patient with hypereosinophilia. J Allergy Clin Immunol. 2010 Jul.126 (1):39-44.
11. Gleich GJ, Schroeter AL, Marcoux JP, et al. Episodic angioedema associated with eosinophilia. N Engl J Med. 1984; 310:1621.
12. Valent P, Klion AD, Roufosse F, et al. Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes. Allergy 2023; 78:47.
13. Kazura JW. Eosinophilia-myalgia syndrome. Cleve Clin J Med. 1991; 58:267.
14. Katz G, Stone JH. Clinical Perspectives on IgG4-Related Disease and Its Classification. Annu Rev Med. 2022; 73:545.
15. Roufosse F, Klion AD, Weller PF. Hypereosinophilic syndromes: treatment. UpToDate. Updated November 30, 2022. https://www.uptodate.com/contents/hypereosinophilic-syndromes-treatment Accessed October 15, 2025.
16. Curtis C, Ogbogu PU. Evaluation and Differential Diagnosis of Persistent Marked Eosinophilia. Immunol Allergy Clin North Am. 2015 Aug. 35 (3):387-402.
17. Klion AD. Approach to the patient with suspected hypereosinophilic syndrome. Hematology Am Soc Hematol Educ Program. 2022 Dec;2022(1):47-54.
18. Shomali W, Gotlib J. World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management. Am J Hematol. 2024;99(5):946-968. doi:10.1002/ajh.27287
19. Rothenberg ME, Klion AD, Roufosse FE, et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008;358(12):1215-1228. doi:10.1056/NEJMoa070812
20. Kuang FL, Makiya MA, Ware JM, et al. Long-Term Efficacy and Safety of Benralizumab Treatment for PDGFRA-Negative Hypereosinophilic Syndrome. J Allergy Clin Immunol Pract. 2025;13(6):1421-1429.e2. doi:10.1016/j.jaip.2025.03.016
21. Halaburda K, Prejzner W, Szatkowski D, et al. Allogeneic bone marrow transplantation for hypereosinophilic syndrome: long-term follow-up with eradication of FIP1L1-PDGFRA fusion transcript. Bone Marrow Transplant 2006; 38:319.

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