What Is Hypereosinophilic Syndrome?
Medically reviewed by Jurairat J. Molina, MD
Hypereosinophilic syndromes (HES) are a rare group of blood disorders associated with an abnormally high number of white blood cells called eosinophils. Eosinophils are important for your immune system’s response to infections and allergic reactions. In people with HES, chronically elevated eosinophil levels can infiltrate the body’s tissues, causing inflammation and organ damage. This may affect your skin, heart, lungs, brain, and digestive tract.
People of all ages can develop HES, but it is most common in people assigned male at birth between ages 30 and 50. Various factors can trigger the development of HES, including genetics, parasitic infections, drug hypersensitivity, blood cancers, and immunodeficiency disorders.
Symptoms of HES vary depending on the organ system affected but commonly include skin rash, fever, fatigue, muscle aches, weakness, and weight loss. Treatment focuses on reducing the number of eosinophils in the blood and may involve corticosteroids, chemotherapy drugs, or targeted therapies, depending on the underlying cause.
Types
Hypereosinophilic syndrome is classified based on the underlying cause. Understanding the type of HES you have helps determine the most effective treatment.
Myeloid hypereosinophilic syndrome (MHES): Develops when an overgrowth of myeloid cells in the bone marrow leads to the overproduction of eosinophils.
Lymphocytic variant hypereosinophilic syndrome (LHES): Develops when abnormal lymphocytes (white blood cells) called T-cells contribute to excessive eosinophil production.
Overlap hypereosinophilic syndromes: Includes eosinophilic diseases that affect a single organ system, such as eosinophilic granulomatosis with polyangiitis (EGPA), or share features with idiopathic HES.
Associated hypereosinophilic syndromes: Develops as a complication of known HES triggers, such as parasitic infections, drug hypersensitivity, or underlying immune deficiencies.
Familial HES: Certain gene mutations, passed down through families, cause this type.
Idiopathic: When there is no identifiable cause of elevated eosinophils, HES is referred to as “idiopathic,” which is a term used when a condition occurs spontaneously or does not have a known cause.
Hypereosinophilic Syndrome Symptoms
Symptoms of hypereosinophilic syndromes vary, depending on which organs and tissues are affected by excess eosinophils. Symptoms common with all types of HES include:
Skin rash, which may be red, itchy bumps (urticaria/hives) or swollen lumps under the skin (angioedema)
Fever
Muscle aches
Weakness
Loss of appetite and/or unintentional weight loss
Cough
Memory problems
Confusion
Dermnet
What Causes HES?
A normal eosinophil blood count is less than 500 cells per microliter (mL) of blood—typically less than 5% of all white blood cells circulating in your blood. Temporary increases in eosinophil counts can occur when your body is fighting a parasitic or viral infection or during an allergic reaction.
Hypereosinophilic syndrome is when eosinophil counts are higher than 1,500/mL for six months or longer. Gene changes and underlying conditions can contribute to the development of hypereosinophilic syndrome, though the exact cause is not always clear.
Gene Changes
Gene changes can cause hypereosinophilic syndromes in two ways: gene fusions and inherited gene mutations.
Gene fusions occur when two formerly separate genes merge into one hybrid (fusion) gene with features from both original genes. In HES, the fusion of the FIP1L1 and PDGFRA genes leads to the creation of proteins that trigger uncontrolled growth of eosinophils.
Inherited gene mutations run in families. Familial HES occurs when mutations in the 5q31-q33 region of chromosome 5 lead to abnormal levels of a pro-inflammatory cytokine (a type of inflammatory protein) called interleukin-5, which controls the growth and mobilization of eosinophils.
Underlying Conditions
Certain conditions can activate immune cells, causing your body to release inflammatory substances that can contribute to excess eosinophil production. These conditions include:
Parasitic, fungal, and viral infections
Allergic reactions and allergy-related disorders, including asthma and atopic dermatitis
Autoimmune disorders, including inflammatory bowel disease (IBD) and connective tissue disorders
Drug hypersensitivity (allergic reaction to over-the-counter or prescription medications or dietary supplements)
Risk Factors
Anyone can develop hypereosinophilic syndrome, but it is more common in people assigned male at birth between the ages of 30 and 50.
Diagnosis
Diagnosing hypereosinophilic syndrome can be a challenge because the symptoms are similar to those in other conditions, such as autoimmune disorders and allergic reactions. Typically, a multi-step approach is taken to rule out other possible causes of your symptoms before diagnosing HES.
Your healthcare provider will review your medical history, including medication use, previous infections, current medical conditions, and family history. They will ask about your symptoms and perform a physical examination to look for signs of HES, such as skin rash or shortness of breath.
Diagnostic tests help provide an accurate diagnosis and determine the underlying cause of HES. Depending on your symptoms, they may order:
Blood tests to measure your complete blood cell count (CBC) and eosinophil count. Blood tests can also measure substances that monitor liver and kidney function, vitamin B12, and tryptase levels (an enzyme that contributes to allergic reactions).
Imaging scans, such as X-rays, computed tomography (CT) scans, and ultrasounds, allow your healthcare provider to views your internal organs to check for damage. A chest X-ray, for example, can show lung damage, and an echocardiogram (ultrasound) shows how your heart is functioning.
Skin biopsy, which can be used to assess the cause of a rash. Your healthcare provider may take a small skin sample and send it to the lab, where a technician will examine it under a microscope to confirm the presence of eosinophils in the tissue.
Bone marrow biopsy, which is done by removing a small amount of bone (usually from the hip bone) to look for abnormalities in white blood cells and measure the amount of eosinophils in the bone marrow.
Allergy testing, such as skin prick or blood tests, can reveal allergies to specific substances (e.g., pollen) and diagnose allergic diseases.
Related: Biopsy: What You Need To Know
Treatments for Hypereosinophilic Syndrome
Treatment for hypereosinophilic syndrome focuses on decreasing high eosinophil levels in your blood, reducing inflammation to prevent organ damage, and slowing disease progression. The treatment your healthcare provider recommends will depend on which organs are involved and the underlying cause of HES.
Corticosteroids
Corticosteroids, such as prednisone, are a first-line treatment for HES. These potent anti-inflammatory drugs are used to suppress eosinophil production and reduce inflammation to prevent organ damage. Steroid therapy is highly effective, returning eosinophil counts to normal or near-normal levels in 85% of those with HES.
Corticosteroids do not cure HES, and eosinophil levels will return to elevated levels when you stop taking the medication. Long-term steroid use can cause side effects, including weight gain, mood changes, high blood pressure, and bone loss.
Interferon Alpha (IFNa)
Interferon Alpha (IFNa) is an immunomodulating medication, meaning it helps change your body's natural immune response. They are delivered via injection into fatty tissue under the skin 3 to 5 times a week.
INFa suppresses HES symptoms, but initially causes flu-like symptoms, such as fever, joint pain, and muscle aches, which will subside over time. Long-term use of INFa can cause serious side effects, including elevated liver enzymes, low blood cell counts, depression and mood disorders, and heart attack.
Monoclonal Antibodies
Monoclonal antibodies are a type of biologic medication. They are lab-made immune system proteins that may be prescribed to people with HES when other treatments are ineffective. Two monoclonal antibodies can treat HES:
Nucala (mepolizumab): Targets and blocks interleukin-5, a cytokine that controls eosinophil growth.
Lemtrada (lemtuzumab): Targets and binds to a protein on the surface of eosinophils (CD52), effectively killing them.
Tyrosine Kinase Inhibitors
Tyrosine kinase inhibitors are enzymes that play a role in activating inflammatory immune cells. Tyrosine kinase inhibitors like Gleevac (imatinib) may help reduce eosinophil counts and control HES symptoms with minimal side effects in people with HES associated with specific gene changes.
Chemotherapy
Chemotherapy drugs, such as hydroxyurea, cyclophosphamide, vincristine, etoposide, and methotrexate, kill fast-growing cells like eosinophils. These are potent drugs with serious side effects (e.g., nausea, vomiting, hair loss, anemia, increased risk of infection), and healthcare providers typically only prescribe them for the most advanced cases of HES.
Prevention
The causes of hypereosinophilic syndromes are diverse and complex, and there is no known way to prevent the condition. If you have risk factors for or a condition related to HES, regular appointments with your healthcare provider and close monitoring of your eosinophil levels can help detect HES early. Timely diagnosis and treatment can help prevent extensive organ damage and slow disease progression.
Related Conditions
People with HES often have additional health conditions, many of which develop as a complication of eosinophils infiltrating and damaging the body’s organs.
Eosinophilic gastrointestinal diseases (EGIDs): Eosinophil infiltration of the gastrointestinal tract can cause symptoms such as abdominal pain, nausea, vomiting, diarrhea, bloating, and weight loss.
Allergic diseases: Many people with HES have allergic diseases, such as asthma, food allergies, and atopic dermatitis. Shared genetic factors and excessive inflammatory responses may play a role in the connection.
Heart disease: Eosinophil infiltration can damage heart muscles and valves, leading to arrhythmias (irregular heartbeat), heart murmurs, thrombus (blood clots), mitral valve insufficiency, or heart failure.
Organ enlargement: The build-up of eosinophils in certain organs, most commonly the spleen and liver, can inflame and enlarge organs in people with HES.
Lung damage: When eosinophils infiltrate lung tissues, lung function can decline and lead to respiratory difficulties like shortness of breath, coughing, and chest pain.
Lungs: Eosinophils can infiltrate and inflame lung tissues, leading to respiratory problems, asthma-like symptoms, coughing, and even interstitial lung disease, impacting how well your lungs function and use oxygen.
Neurological complications: Eosinophils infiltrating the nervous system can lead to seizures, neuropathy (nerve damage), and encephalopathy (e.g., memory problems and confusion).
Living With HES
While there’s no cure for hypereosinophilic syndrome, taking a proactive approach to your health and following your treatment plan can help manage symptoms, slow disease progression, and lower your risk of extensive organ damage and complications. With treatment, most people with HES enjoy productive, fulfilling lives. Without treatment, HES can cause life-threatening complications.
Symptoms of HES can have a significant impact on your daily life, and you may need to make adjustments to your routine. Ak family and friends for support on your more difficult days or talk to your healthcare provider about your challenges. They may have support resources you can access or adjust your treatment plan if your symptoms worsen.
Frequently Asked Questions
What is the life expectancy of someone with HES?
The life expectancy of someone with HES depends on the type and severity of HES, which organs are involved, and their response to treatment. Thanks to advancements in HES treatments, more than 80% of people with HES live five years or longer after diagnosis.
What happens if HES is left untreated?
Untreated HES can cause extensive damage to the heart, lungs, gastrointestinal tract, and other organs, increasing your risk of life-threatening complications.
Is hypereosinophilic syndrome a type of leukemia?
There are several types of hypereosinophilic syndrome, and most are not a type of leukemia. However, a subtype of HES—chronic eosinophilic leukemia—is a rare form of leukemia that is a type of idiopathic HES.
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