What Are Hypereosinophilic Syndromes?

Hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by high levels of eosinophils, which cause damage to organs, including the skin, lungs, heart, and gastrointestinal tract. The majority of HES are considered benign (noncancerous) conditions but a subset may evolve into cancer.

Definition

Hypereosinophilia is defined as an absolute eosinophil count greater than 1500 cells/microliter on two complete blood counts (CBC) on two separate occasions separated by at least one month and/or confirmation of tissue hypereosinophilia on biopsy. Hypereosinophilia in the tissues is defined based on the area of biopsy.

On a bone marrow biopsy, hypereosinophilia is defined when more than 20% of nucleated cells are eosinophils. In other tissues, it is defined as "extensive" infiltration of eosinophils into the tissue in the opinion of the pathologist (physician reviewing the biopsy). 

Several conditions can result in eosinophilia but these rarely cause the tissue damage seen in HES. Eosinophilia can be broken down into three categories: mild (500 to 1500 eosinophils/microliter), moderate (1500 to 5000 eosinophils/microliter), and severe (greater than 5000 eosinophils/microliter).

Types

HES can be divided into three large categories:

• Primary (or neoplastic): In primary HES, a genetic change stimulates the bone marrow to accelerate eosinophil production similar to polycythemia vera or essential thrombocythemia.
• Secondary (or reactive): In secondary HES, the underlying condition (parasite infection, lymphoma, etc) produces proteins (called cytokines) that stimulate eosinophil production. 
• Idiopathic: Idiopathic HES is a diagnosis of exclusion, meaning that no other cause of eosinophilia can be identified.
  

Symptoms

The National Institute of Health Genetic and Rare Diseases reports symptoms of HES are based on the area affected and may include:

• Skin: rashes, itching, and eczema
• Lungs: asthma, cough, difficulty breathing, recurrent upper respiratory infections, and pleural effusion
• Heart: congestive heart failure, cardiomyopathy, pericardial effusion, and myocarditis
• Nervous system: vertigo, paresthesia, speech impairment, and visual disturbances
• Blood: deep venous thrombosis and anemia
• Musculoskeletal: arthritis, muscle inflammation, muscle aches, and joint pain
• Gastrointestinal (GI) tract: abdominal pain, vomiting, and diarrhea

Diagnosis

Eosinophils are one of the five types of white blood cells (neutrophils, lymphocytes, monocytes, eosinophils, and basophils). The initial diagnostic test is a complete blood count. An eosinophil count greater than 1500 cells/microliter on 2 occasions justifies further testing. Initially, more common causes of eosinophilia should be eliminated. 

Once HES is suspected, the evaluation is focused on looking for organ involvement. Evaluation of the heart would include an electrocardiogram (ECG) and echocardiogram (ultrasound of the heart). Lung function testing should be performed. Computed tomography (CT) will be used to look for any signs of HES in the lungs or abdomen. 

Additional testing will be focused on determining whether there is any evidence for myeloproliferative neoplasm. This would include blood work and a bone marrow aspirate/biopsy. Tissue for the bone marrow will be tested for genetic changes associated with HES. If there is an increased number of mast cells, testing will be sent to look for systemic mastocytosis (another type of myeloproliferative neoplasm).

Treatment

Your treatment will be determined by your type of hypereosinophilic syndrome and severity of your symptoms. It is uncommon to need treatment right at diagnosis, but rarely severe HES may require immediate treatment. 

• Steroids: Steroids like prednisone and methylprednisolone may be used.
• Imatinib: Imatinib is an oral medication used to treat cancer called a tyrosine kinase inhibitor. 
• Hydroyxurea: Hydroxyurea is an oral chemotherapy medication. It may take up to 2 weeks to see a response to this medication.

In patients for whom steroids, imatinib, and hydroxyurea are either not indicated or ineffective, there are a variety of other agents that may be warranted, including vincristine, an intravenous (IV) chemotherapy. A positive response to this drug means the eosinophil count can decrease within hours of administration.  

If there are features of myeloproliferative neoplasm (elevated vitamin B12 levels, enlarged spleen, atypical eosinophils, etc.), initial treatment is imatinib. If there is cardiac involvement, steroids are added. If imatinib is not effective, there are several similar medications that may be used. The majority of people with HES do not require treatment but require careful monitoring for organ damage, development of blood clots (thrombosis), and disease progression. If there is organ involvement, steroids are first line therapy. Because long-term steroid use is associated with many side effects, once symptoms are under control, you may be transitioned to another medication like hydroxyurea, alpha interferon, or methotrexate for continued treatment. 

As seen above, steroids are a mainstay of treatment. Prior to starting steroids, it is very important to determine if you are at risk for a parasite infection called Strongyloides. Steroids can worsen a Strongyloides infection significantly. If you require urgent treatment and there is any concern that you have a Strongyloides infection, you will be treated for the infection (oral medication for 2 days). 

A Word From Verywell

Learning you have hypereosinophilic syndrome can be frightening. Fortunately, the large majority of people with HES will not require treatment. For those who do, there are several options and even more are currently being studied.