Hypereosinophilic syndrome (NORD)

Hypereosinophilic syndrome, or HES, is a group of disorders that are characterized by elevated levels of eosinophils in the blood, called eosinophilia, as well as accumulation of eosinophils in at least one organ in association with tissue damage and dysfunction.  

In HES, large numbers of eosinophils, a type of white blood cells accumulate and become activated, releasing excess amounts of their cellular constituents, most notably their granules, which instead of being helpful, are toxic to a variety of tissues, resulting in organ dysfunction.

There are 3 main types of HES categorized based on the underlying cause: primary (or neoplastic), secondary (or reactive), and familial or hereditary.

Primary or neoplastic HES is caused by de novo genetic changes (or variants), which means that a new DNA sequence change is typically responsible. The DNA change is not inherited but occurs later in life (called a de-novo variant). The result is myeloid cell expansion, or expansion of an abnormal clone of T cells, a type of immune cell, that stimulates production of eosinophils. The myeloid expansion is often referred to as hematological or neoplastic HES whereas the T cell expansion is referred to as clonal lymphoid HES.

Secondary HES, also known as reactive HES, is the most common and is caused by a response to a secondary stimulus such as an infection, like from a parasite or an underlying inflammatory process, drugs, such as anti-seizure medications, or some cancers.

Hereditary or familial type HES is characterized by a history of eosinophilia in several family members and is caused by inherited gene changes. This form of HES is often more benign.

Individuals with HES may have no symptoms, mild symptoms, or severe symptoms, like heart failure or stroke. Symptoms may come on gradually or all of a sudden. Symptoms may be general, such as fatigue, fever, muscle pain, and night sweats, or specific to the affected organ, like the skin, lungs, gastrointestinal tract, heart, and nervous system.

The skin is the most commonly affected organ, and HES can cause itching, rash, or hives. When the lungs are involved, individuals may experience shortness of breath, coughing, and wheezing. Gastrointestinal symptoms include weight loss, difficulty swallowing, abdominal pain, vomiting, diarrhea, and jaundice, or yellowing of the skin. Heart symptoms include cough, shortness of breath, chest pain, palpitations, or heart failure. Nervous system involvement can cause numbness or tingling in the hands or feet, muscle and joint pain, confusion, memory loss, and even strokes.

HES is diagnosed when the eosinophil count is persistently elevated greater than 1,500 cells per microliter of blood, there is evidence of organ or tissue damage, and other diagnoses have been eliminated.

Specific testing typically involves extensive blood work, genetic testing, and other tests dependent upon symptoms. For example, if an individual with eosinophilia has gastrointestinal symptoms, a CT scan of the abdomen or endoscopy and biopsy is often performed. In those with heart involvement, an electrocardiogram, chest x-ray, echocardiogram, or ultrasound of the heart may be done.