What are Hypereosinophilic Syndromes?

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Hypereosinophilic Syndromes (HES) are a group of rare disorders in which high numbers of eosinophils are found in the blood and tissue, for prolonged period of time (6 months or more) for which a cause cannot be found. While most people have blood eosinophil levels of less than 500/ml, those with HES typically have blood levels of more than 1,500/ml.

Continuous presence of high number of eosinophils in blood can eventually cause multiple organ tissue damage as these eosinophils infiltrate different tissues and cause inflammation. HES can affect any organ in the body, including the stomach and intestines, the heart, lungs, skin and other organs.

Causes

The cause of HES is not known.

Who is Affected?

While both men and women may be affected by HES, the disease is more commonly seen in males ages 20-50. While it is more commonly diagnosed in adulthood, it has also been diagnosed in children.

Symptoms

The symptoms of HES may vary widely, depending on the part of the body that is affected. Symptoms may include cough, fever, fatigue, shortness of breath and wheezing. The symptoms of HES are also common in many other medical problems, including autoimmune diseases, allergic disease, cancer, and drug reactions, making HES more difficult to diagnose.

Diagnosis

Since many different problems can cause high numbers of eosinophils in the blood, higher than normal blood eosinophil number alone does not mean an individual has, or will develop, HES.

Criteria has been developed that must be fulfilled for an individual to be diagnosed with HES.

1. Peripheral blood eosinophilia (high numbers of eosinophils in the blood) more than 1500 eosinophils, for at least six months’ duration.
2. End-organ (heart, lungs, GI tract, brain, skin, etc) involvement with eosinophil tissue infiltration (invasion) and injury.
3. Exclusion of known other causes for the eosinophilia such as parasitic infections and certain bone marrow/blood diseases.

Tests are needed to diagnose HES and include a complete blood cell count, including eosinophil count, blood samples for liver and kidney function, and blood tests for Vitamin B12 and tryptase.

Depending on symptoms and test results, other studies may be performed. For instance, ultrasound (echocardiography) is used to look at the function of the heart. A chest x-ray may be done to examine the lungs. A bone marrow biopsy is recommended in patients suspected of having HES. It commonly reveals high number of eosinophils and some other abnormalities, suggestive of an innate bone marrow/blood disease of eosinophils. Therefore, HES is classified as hematologic neoplasm (disease of the blood and bone marrow) and is part of the larger group of Myeloproliferative Neoplasms.

Closely related disease to HES is chronic eosinophilic leukemia (CEL). Major difference, in simple terms, is that in CEL all eosinophils found in the bone marrow and blood are proven to be identical (also called “clonal”, meaning that all originate from the same, one, abnormal eosinophil).

The disease may be diagnosed and monitored by a team of specialists, such as allergist/immunologist, hematologist, and/or cardiologist.

Treatment

When treating HES, the goal is to reduce the eosinophils in the blood, prevent organ damage, and slow disease progression. Treatments vary based on organs involved, disease severity, and other medical issues and may include the following.

• Corticosteroids (e.g., prednisone) are often the first-line treatment for HES. Many I-HES patients can be treated with low dose oral corticosteroids for long periods of time with fairly good success. Some variants such as L-HES may require higher doses. Corticosteroids fight inflammation and decrease the number of eosinophils. However, the eosinophils and symptoms generally return once corticosteroids are lowered or stopped. Long-term corticosteroid use (especially at doses greater than 10 mg/day) can be associated with serious side effects such as adrenal insufficiency, avascular necrosis, osteoporosis, infections, and stunted growth.
• Biologic medicines are treatments that target specific parts of the immune system. In conditions like HES, these medicines can help lower eosinophil levels and improve symptoms. They are usually given as injections or infusions. In the U.S., there are currently two biologic medications that are FDA-approved to treat HES:
  • Mepolizumab (Nucala®) targets a signal called IL-5 and was approved in 2020 to treat people ages 12 and older with hypereosinophilic syndrome (HES) lasting six months or longer without an identifiable non-hematologic secondary cause.
  • Benralizumab (Fasenra®), another IL-5–targeting treatment, was approved in May 2026 to treat HES in people ages 12 and olde rwithout an identifiable non-hematologic secondary cause..
  • Other biologics that have been used in severe or treatment-resistant HES cases are approved in the U.S. for other conditions but not specifically HES (“off-label” use). These include reslizumab and alemtuzumab.

• Imatinib mesylate is a tyrosine kinase inhibitor for some M-HES patients, such as those with PDGFRA rearrangement. Approximately 10-20% of patients with M-HES have a genetic abnormality involving activating tyrosine kinase mutations that cause their HES. More specific testing can help determine if a patient might benefit from this therapy.
• Interferon alpha (IFN-α) injections are used to suppress symptoms related to HES. Many patients experience flu-like symptoms from these injections (e.g., fever, chills) and therapy may need to be discontinued due to side effects.
• Other treatments a doctor may prescribe include medications to suppress the immune system (such as cyclosporine, mycophenolate, hydroxyurea, methotrexate), and alternative treatments for severe/ advanced cases of HES include anti-neoplastic agents or chemotherapy to deplete eosinophils (e.g., chlorambucil, cladribine, cyclophosphamide, etoposide, vincristine). These agents have many potential side effects that would be discussed by your doctor(s) if they are needed.

Talk to your doctor to determine the best treatment option for you. To learn about clinical trials for HES, visit apfed.org/clinicaltrials.

Prognosis

The prognosis in HES depends on the organ systems involved, disease severity and response to therapy. Outcomes can vary greatly from one person to the next. There is no cure. If HES is left untreated, the disease may be fatal. Your doctor can best answers questions about your specific prognosis in HES.

Other Resources

HES Patient Conference

On March 23, 2018, APFED hosted a Hypereosinophilic Syndromes Patient Education and Drug Development Conference in Rockville, MD. Below are the meeting materials and the webcast recording.

• Conference agenda (PDF)
• Speaker bios (PDF)
• Panel discussion transcripts (PDFs)
• View the session recordings (YouTube playlist)

Please note: The recording does not include Dr. Klion’s presentation. We will update the recording to include this presentation as soon as the research that was discussed is published and we are able to show the material. Please also note that polling questions and call-in instructions that are included in the webcast were only operational during the live event are no longer accessible.

Educational Content

• Hypereosinophilic Syndromes Brochure (PDF)
• APFED HES Patient Education Kit (PDF)

Websites

• American Academy of Allergy Asthma and Immunology
• Cure HES, Patient Blog
• Genetic and Rare Diseases (GARD) Information Center
• Global Genes
• National Institute of Health (NIH)
• National Organization for Rare Disorders

APFED’s Eos Connections Online Community, Inspire Network

Hypereosinophilic Syndrome

Videos and Webinars

https://www.youtube.com/watch?v=KG9erSOVfPo

Professional Education

Easing the Burden of Hypereosinophilic Syndrome: An Animated Exploration of the Role of Targeted Therapy to Improve Patient Outcomes
APFED is proud to partner with PeerView Institute for Medical Education (PVI) to bring you this new animated program
Featuring Paneez Khoury, MD, MHSc, FAAAAI and patient Christine Singer.

Reference List

• Warrell DA, Cox TM, Firth JD, Benz EJ. Oxford Textbook of Medicine. Fourth Ed. Oxford University Press. 2003
• 2Klion AD, Bochner BS, Gleich GJ, et al, and The Hypereosinophilic Syndromes Working Group. Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report. J Allergy Clin Immunol. Jun 2006;117(6):1292-302.
• Simon HU, Rothenberg ME, Bochner BS, Weller PF, Wardlaw AJ, Wechsler ME, et al. Refining the definition of hypereosinophilic syndrome. J Allergy Clin Immunol. Jul 2010;126(1):45-9.
• Klion A. Hypereosinophilic syndrome: current approach to diagnosis and treatment. Annu Rev Med. 2009;60:293-306.
• Schwartz LB, Sheikh J, Singh A. Current strategies in the management of hypereosinophilic syndrome, including mepolizumab. Curr Med Res Opin. Aug 2010;26(8):1933-46.

Authored by Srdan Verstovsek, MD, PhD, Leukemia Department, MD Anderson Cancer Center, Houston, TX; and Mary Jo Strobel. © American Partnership for Eosinophilic Disorders (APFED) 2008-2014. All rights reserved. Updated 9/14.