What Are Hypereosinophilic Syndromes?

A Review of Symptoms, Diagnosis, and Treatment of Hypereosinophilic Syndromes

Patient and Physician Discussion
Patient and Physician Discussion. Hero Images/Creative RF/Getty Images

Hypereosinophilic syndromes (HES) are a group of rare disorders characterized by high levels of eosinophils (eosinophilia) which cause damage to organs (skin, lungs, heart, gastrointestinal tract). The majority of people are over the age of 20 at diagnosis but it can occur in children. The majority of HES are considered benign (non-cancerous) conditions but a subset are considered myeloproliferative neoplasms which can evolve into cancer.

 

How Is Hypereosinophilia Defined?

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 percent of nucleated cells are eosinophils. On 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.

What Are the Categories of HES?

HES can be divided into three large categories:  primary (or neoplastic), secondary (or reactive), and idiopathic. Idiopathic HES is a diagnosis of exclusion, meaning that no other cause of eosinophilia can be identified. In primary HES, a genetic change stimulates the bone marrow to accelerate eosinophil production similar to polycythemia vera or essential thrombocythemia.

In secondary HES, the underlying condition (parasite infection, lymphoma, etc) produces proteins (called cytokines) that stimulate eosinophil production.  

What Are the Symptoms of HES?

Symptoms of HES are based on the area affected and may include:

  • Skin:  eczema, thickening of the skin, hives,
  • Lungs:  cough, shortness of breath, wheezing
  • Heart: chest pain, difficulty breathing, 
  • Neurologic disease
  • Blood clots (thrombosis)
  • Eyes: Blurred vision
  • Gastrointestinal (GI) tract:  weight loss, abdominal pain, vomiting, diarrhea

How Is HES Diagnosed?

As mentioned above, 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 are an increased number of mast cells, testing will be sent to look for systemic mastocytosis (another type of myeloproliferative neoplasm).

What Are the Treatment Options?

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.  
  • Vincristine:  Vincristine is an intravenous (IV) chemotherapy that can be used.  If you respond, your eosinophil count can decrease within hours of administration.   
  • Hydroyxurea:  Hydroxyurea is an oral chemotherapy medication. It may take up to 2 weeks to see a response to this medication.

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 being currently studied.  

Sources

Roufosse F, Klion AD, Weller PF. Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and diagnosis and Hypereosinophilic syndromes: Treatment.  In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on July 5, 2016.)

Continue Reading