What is Hypereosinophilic Syndrome?
Hypereosinophilic syndrome, also known as HES, is a rare and complex set of diseases. These diseases are marked by consistently high levels of a type of white blood cell called eosinophils, which can lead to tissue damage. Eosinophils play a key role in inflammation, which is a common factor in many illnesses.
The doctors use certain criteria to diagnose HES:
- The person has more than 1.5 x 109 eosinophils in their bloodstream, confirmed on two different checks at least a month apart.
- More than 20% of all the cells in the bone marrow (which produce blood cells) are eosinophils.
- A pathologist (a doctor who diagnoses disease by studying body tissue) determines that there’s extensive infiltration (movement into tissue) by eosinophils or there’s a noticeable amount of eosinophil proteins in the tissue.
- There’s evidence of injury to organs or tissue that’s likely caused by an excess of eosinophils in the tissue (tissue hypereosinophilia).
- Other diseases or conditions that could cause the organ damage have been ruled out.
What Causes Hypereosinophilic Syndrome?
Hypereosinophilic syndrome (HES) is a disease that happens when you have too many eosinophils (a type of white blood cell) in your body. After looking at a patient’s symptoms and history, doctors can divide HES into 5 different types. The types are important because they can help a doctor know how to treat the disease.
The first type is primary, or neoplastic HES. This means HES is a type of cancer, like leukemia, that is causing the body to make too many eosinophils. One subtype of this type is myeloid HES (M-HES), which includes different genetic changes in the cells. Some of these changes involve certain genes such as FIP1L1-PDGFRA fusion gene, JAK2 point mutation, and fibroblast growth factor receptor 1 (FGFR1) gene changes. Another subtype is the T-cell lymphocytic HES, which is caused by special immune cells in the body creating too many eosinophils.
The second type is secondary, or reactive HES. This means that another disease is causing the body to produce eosinophils. Examples include helminth infections, a disease where the body can swell in certain parts, or eosinophilic granulomatosis with polyangiitis (EGPA), which is a type of inflammation of blood vessels.
The third type is familial HES. This means that other family members have had the same disease, but doctors don’t know why.
The fourth type is idiopathic HES. This is HES where doctors can’t find a reason why the body is making too many eosinophils, which can lead to damage in different parts of the body.
The last type is Organ-Restricted HES. In this case, high levels of eosinophils are only present in a specific organ or tissue and damage that specific part, but the blood levels of eosinophils are normal.
Risk Factors and Frequency for Hypereosinophilic Syndrome
The exact number of people affected by hypereosinophilic syndromes (HES) is not known. However, a study in 2010 gave an estimated rate between 0.16 and 0.36 per 100,000 people. This syndrome affects more people between the ages of 20 to 50 but there are reported cases in children as well.
Studies show that the types of HES are about the same in children and adults. Children with immune system problems often have secondary HES, more stomach complaints, high levels of a certain type of white blood cell called eosinophils, and fewer lung issues in comparison to adults.
- The exact number of people with hypereosinophilic syndromes for now remains unknown.
- Estimated rates are between 0.16 and 0.36 per 100,000 people, based on a 2010 study.
- This condition is more commonly seen in people aged 20 to 50, but can also affect children.
- The types of HES seem to be similar between adults and children.
- Children with immune issues often have a secondary form of HES, suffer more from stomach complaints, and have higher levels of eosinophils.
- Children with HES typically have fewer lung-related issues in comparison to adults.
Signs and Symptoms of Hypereosinophilic Syndrome
Hypereosinophilic syndrome (HES) is an ailment that can lead to a wide variety of health problems due to its influence on numerous body systems. Between 2001 to 2006, around 37% of patients suffering from HES had skin-related issues, 25% showed lung-related symptoms, 14% had stomach-related problems, 5% encountered heart-related issues, and 4% experienced brain-related symptoms.
Skin conditions related to HES can range from mild irritations like eczema, red skin, skin hardening, hives, and angioedema to more severe ones like skin lesions, itchiness, and rashes on the body and limbs. In certain circumstances, severe skin issues might be indicative of cutaneous T-cell lymphoma associated with HES.
People with HES often show symptoms similar to asthma, such as shortness of breath, coughing, and wheezing. Looking at chest x-rays or CT scans could reveal abnormalities like patchy infiltrates and consolidation, and in fewer cases, lung nodules, pleural effusion, chest lymph node swellings, and blood clots in the lungs.
- Skin conditions like eczema and hives
- Lesions, itching, and rashes on body and limbs
- Shortness of breath, coughing, and wheezing
- Abnormalities on chest x-rays or CT scans
Issues with the digestive system could manifest as difficulty swallowing, weight loss, stomach pain, nausea, vomiting, and diarrhea due to conditions like inflammation in the digestive tract, chronic active hepatitis, liver disease, and Budd-Chiari syndrome.
Heart-related symptoms due to HES are more commonly seen with a certain HES variant and can include signs of heart failure like breathing difficulty, chest pain, cough, and heartbeat sensations. These symptoms could be a sign of severe problems like pericarditis, myocardial ischemia, and thrombus inside the heart.
Heart damage due to HES typically takes place in three stages. Initially, there’s the necrotic stage, usually silent and doesn’t show any signs. Subsequently, the intermediate phase sees the formation of thrombus, possibly leading to blood clot-related issues. Lastly, the fibrotic stage involves scarring of the heart tissue leading to restrictive cardiomyopathy and life-threatening heart rhythm disorders.
Neurologic manifestations of HES could be central, like encephalopathy and organic psychosyndrome, or peripheral, which account for more than half of HES-related neurologic symptoms and include peripheral neuropathy, mononeuropathy multiplex, autonomic neuropathy, and polymyositis.
Other issues related to HES can arise from blood clots, such as clot inside the heart, encephalopathy likely resulting from microvascular occlusion, peripheral neuropathy, and sinus thrombosis.
Testing for Hypereosinophilic Syndrome
If you are being evaluated due to increased levels of eosinophils (a type of white blood cell) in your blood, it’s important for your doctor to gather as much information about your health history as possible. This can help them identify treatable causes, such as parasitic infections (screened by stool tests) or negative reactions to drugs, including natural supplements. They’ll also check for signs of organ damage, which might not be noticeable at first and may not directly correlate with the high levels of eosinophils.
In situations where hypereosinophilic syndrome (HES) is suspected but there’s no obvious cause of the increased eosinophils, further investigation is necessary to determine the specific form of HES. Your doctor may order tests such as a complete blood count (CBC), comprehensive blood chemistries, liver enzymes, kidney function tests, creatine kinase, and troponin levels. Additionally, they might request imaging tests such as an electrocardiogram, echocardiogram, pulmonary function tests, chest X-ray, CT scan of the chest and abdomen, and even tissue biopsies if needed.
In order to better understand the root cause of HES, the doctors may also do some specialized testing. For instance, Fluorescence in situ hybridization (FISH), which helps to detect specific genetic changes, or flow-cytometry, which identifies specific types of cells. In some cases, you might need a bone marrow aspiration and biopsy, which can reveal increased levels of eosinophils and their precursors, and also allows for further testing.
Other molecular-level studies might be used to detect the presence of certain abnormalities known as fusion genes, as well as other types of mutations. These tests can help to confirm a diagnosis of HES.
Interestingly, different variants of HES may be associated with very specific characteristics. For example, M-HES variants are often accompanied by increased serum B12 and the presence of certain fusion genes. You might also experience conditions like anemia, low platelet count (thrombocytopenia), increased levels of a protein called tryptase, and an enlargement of the liver or spleen. L-HES, on the other hand, tends to involve skin symptoms, and molecular testing could identify abnormal T cell markers. Additional tests might be needed to check for exposure to the Epstein-Barr virus (EBV), since chronic infection can drive L-HES. Other tests noticed in L-HES cases include keys that point to elevated levels of certain substances in the blood, such as specific immunoglobulins (proteins that function as antibodies), TARC (thymus activation-regulated chemokine), and IL-5 (interleukin-5).
Treatment Options for Hypereosinophilic Syndrome
The need for treatment in people with HES, a condition of high eosinophil count in blood, depends on the cause and disease severity. Patients whose cause is not determined should undergo a comprehensive assessment to identify treatable factors and associated gene abnormalities. The aim of the treatment is to reduce the eosinophil count, improve symptoms, and prevent disease progression. The treatment timing depends on the severity of the disease and the impact of symptoms on the patient’s wellbeing.
Eosinophils are a type of white blood cell that play a role in our body’s immune response. High levels can cause damage to tissues and organs. Severe HES is characterized by very high eosinophil counts and the involvement of the nervous and pulmonary systems. Treatment in severe HES includes high-dose intravenous corticosteroids, which are drugs that reduce inflammation, and infection checks. A positive response to treatment will see a 50% reduction in eosinophil count within 24 hours.
When treatment is considered for stable HES, the initial approach depends on the variant of HES. Systemic glucocorticoids, which are steroids that reduce inflammation, are the main form of treatment. If steroids are not effective, other types of medication, like imatinib, may be used. For secondary HES, where the high eosinophil count is a result of another condition or disease, the treatment should be directed at the underlying cause.
Imatinib mesylate, a type of cancer drug, has shown positive results in treating a specific variant of HES at a certain dosage. Its mechanism is to block the action of certain proteins in the body that cause the eosinophils to proliferate uncontrollably.
Hydroxyurea, a type of chemotherapy drug, can be used for people who do not respond to steroids. Its mechanism targets the development of eosinophils, though it is less effective when an acute reduction in eosinophil count is needed.
Interferon-α (IFN-α), a protein our bodies make to fight off infections, can target eosinophils and inhibit other cells that contribute to high eosinophil count. It has proven effective, especially when used with steroids. However, IFN-α can cause a range of side effects that may interrupt treatment.
Immunomodulatory agents, such as mepolizumab and benralizumab, both targeting a specific chemical messenger involved in the growth of eosinophils, have also proven effective in certain HES cases. In a major trial assessing mepolizumab, 84% of patients managed to reduce their steroid dosage without an increase in the clinical activity of HES. This suggests mepolizumab could be a good alternative to taking steroids.
What else can Hypereosinophilic Syndrome be?
The process of diagnosing Hypereosinophilic Syndrome (HES) can involve checking for various conditions depending on the severity of the eosinophilia, a condition characterized by a higher than normal number of a certain type of white blood cell.
In milder cases, doctors often look for signs of reactive eosinophilia linked to infectious and parasitic diseases. This involves a careful health assessment, taking a detailed personal history, conducting thorough physical exams, and testing for signs of ova, parasites, and worm infections. In addition, medications or dietary supplements could be contributing to the issue, so it’s important to rule these out.
For more severe cases of HES, blood-related and other kinds of cancerous diseases become a possibility. One example is acute eosinophilic leukemia, which is marked by an elevated amount of immature white blood cells in the peripheral blood, bone marrow, or tissues. Identifying it requires looking for more than 10% blasts in the marrow, which distinguishes it from HES. Chronic myeloid leukemia is another possible diagnosis. Unlike HES, it usually doesn’t cause complications due to eosinophilia and can be distinguished by the detection of a particular molecule called BCR:ABL fusion mRNA.
Systemic mastocytosis with eosinophilia is another condition to rule out. It differs from HES based on the presence of D816V mutations in the KIT gene, its equal distribution among sexes (unlike HES, which is more common in men), and a lower ratio of the eosinophil count to serum total tryptase than seen in HES.
Lastly, doctors should consider Eosinophilic Granulomatosis with Polyangiitis (EGPA) during the HES diagnostic process. This condition stands out from HES due to the presence of inflammation in the blood vessels.
What to expect with Hypereosinophilic Syndrome
The outlook for patients with Hypereosinophilic Syndrome (HES), a condition marked by high numbers of eosinophils (a type of white blood cell) in the blood or tissues, can greatly vary. In some instances, symptoms may be mild and manageable through regular check-ups and observation. However, in severe cases, HES may lead to very serious conditions, including irreversible heart failure or leukemia, a type of blood cancer.
Thankfully, in recent years, the outlook for HES patients has improved due to advancements in medicine. These advancements include earlier detection of complications, improved surgical approaches to manage heart issues, and a wider range of treatments targeting the root cause of HES.
Additioanlly, ongoing research into understanding different strains of HES and how it affects the body may lead to even better treatment strategies in the future, potentially enhancing a positive outcome for patients.
Possible Complications When Diagnosed with Hypereosinophilic Syndrome
The complications that arise from HES, or Hyper-Eosinophilic Syndrome, depend heavily on the type and extent to which the disease affects different organs within the body. Some of the most serious complications include leukemias, which are types of cancer that affect the blood and bone marrow, as well as irreversible heart failure. Conditions affecting the heart’s valves and muscles such as endocarditis and severe restrictive cardiomyopathy, respectively, can also affect individuals with HES. These conditions can cause irregular heart rhythms due to changes within the heart’s electrical system.
Here are the most severe HES complications:
- Leukemias (types of blood and bone marrow cancer)
- Irreversible heart failure
- Endocarditis (inflammation of the heart’s inner lining)
- Severe restrictive cardiomyopathy (a disease of the heart muscle)
- Ventricular arrhythmia, or irregular heart rhythms, due to changes in the heart’s electrical system
Preventing Hypereosinophilic Syndrome
If you’re experiencing several symptoms that don’t seem to have a clear cause, such as shortness of breath, chest pain, coughing, fevers, chills, a rapid heartbeat, stomach inflammation, or skin conditions like eczema or dermatitis, it’s important that you seek medical help. When you visit your doctor, make sure to share as much information as possible. This includes your past medical history, any recent travels, your social habits, the medicines you’re currently taking, and any over-the-counter supplements. All these details can help your doctor determine what might be causing your symptoms.
