Hypereosinophilic syndrome (HES) refers to a rare group of conditions that are associated with persistent eosinophilia with evidence of organ involvement. Signs and symptoms vary significantly based on which parts of the body are affected. Although any organ system can be involved in HES, the heart, central nervous system, skin, and respiratory tract are the most commonly affected. The condition was originally thought to be "idiopathic" or of unknown cause. However, recent advances in diagnostic testing have allowed a cause to be identified in approximately a quarter of cases. Management varies based on the severity of the condition and whether or not an underlying cause has been identified but generally includes imatinib or corticosteroids as an initial treatment.

When the term hypereosinophilic syndrome (HES) was originally coined in 1975, the condition was thought to be 'idiopathic' or of an unknown cause. Today, in approximately 3/4 of cases, the underlying cause still remains unknown. However, recent advances in diagnostic techniques have lead researchers to believe that some people affected by HES may have eosinophilia due to a variety of causes, including:

• Myeloproliferative neoplasms or other disorders that affect the bone marrow (myeloproliferative disorders). This form is called myeloproliferative HES.
• Increased production of interleukin-5 (a protein produced by certain types of white blood cell). This form is called lymphocytic HES.
• A change (mutation) in an unknown gene passed down through a family. This form is called familial HES.

The signs and symptoms of hypereosinophilic syndrome can vary significantly depending on which part(s) of the body are affected. Frequent symptoms listed by body system include:

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

Affected people can also experience a variety of non-specific symptoms such as fever, weight loss, night sweats and fatigue.

The treatment and management of hypereosinophilic syndrome (HES) varies based on the severity of the condition and if an underlying cause for the high levels of white blood cells (eosinophilia) has been identified.  Medications have been developed that target specific causes of HES. For HES without an identified cause, treatment is focused on managing the symptoms. Specialists involved in the care of someone with HES may include:

• Hematologist
• Oncologist
• Immunologist
• Infectious disease specialist
• Cardiologist
• Pulmonologist

A diagnosis of hypereosinophilic syndrome is based on the following criteria:

• Persistent eosinophilia, as defined by blood counts showing increased numbers of eosinophils (greater than 1500 eosinophils/uL) for at least 6 months
• Signs and symptoms of organ involvement
• No evidence of other conditions that can cause eosinophilia*

*Due to advances in the diagnostic techniques, a specific cause of eosinophilia can be identified in a proportion of cases that would have otherwise been classified as idiopathic hypereosinophilic syndrome

Although most cases of hypereosinophilic syndrome (HES) are not inherited, some cases do appear to be passed down through a family. In these families, the exact underlying genetic cause is unknown, but the genetic change (mutation) is thought to be inherited in an autosomal dominant manner. In autosomal dominant conditions, an affected person only needs a change (mutation) in one copy of the responsible gene in each cell. In some cases, an affected person inherits the mutation from an affected parent. Other cases may result from new (de novo) mutations in the gene. These cases occur in people with no history of the disorder in their family. A person with an autosomal dominant condition has a 50% chance with each pregnancy of passing along the altered gene to his or her child.