The hypereosinophilic syndrome (HES) is a disease characterized by a persistently elevated eosinophil count

Eosinophilia

Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...

 (≥ 1500 eosinophils/mm³) in the blood for at least six months without any recognizable cause, with involvement of either the heart

Heart

The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

, nervous system

Nervous system

The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...

, or bone marrow

Bone marrow

Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

.

HES is a diagnosis of exclusion, after clonal eosinophilia (such as leukemia) and reactive eosinophilia (in response to infection, autoimmune disease, atopy, hypoadrenalism or cancer) have been ruled out.

There are some associations with chronic eosinophilic leukemia

Chronic eosinophilic leukemia

Chronic eosinophilic leukemia is a disease in which too many eosinophils are found in the bone marrow, blood, and other tissues. CEL may stay the same for many years, or it may progress quickly to acute leukemia. It is generally caused by overactivation of the oncogene PDGFRA through a chromosome...

 as it shows similar characteristics and genetic defects.

If left untreated, HES is progressively fatal. It is treated with glucocorticoids such as prednisone. The addition of the monoclonal antibody mepolizumab

Mepolizumab

Mepolizumab is a humanized monoclonal antibody that recognizes interleukin-5 , and is used to treat certain kinds of asthma and white blood cell diseases....

 may reduce the dose of glucorticoids.

Classification

In the heart, there are two forms of the hypereosinophilic syndrome, endomyocardial fibrosis and Loeffler's endocarditis.

• Endomyocardial fibrosis (also known as Davies disease) is seen in tropical areas.
• Loeffler's endocarditis does not have any geographic predisposition.

Signs and symptoms

As HES affects many organs at the same time, symptoms may be numerous. Some possible symptoms a patient may present with include:

• Cardiomyopathy
  Cardiomyopathy
  Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...
  
  
• Skin lesions
• Thromboembolic disease
• Pulmonary disease
• Neuropathy
• Hepatosplenomegaly
  Hepatosplenomegaly
  Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...
  
  
• Reduced ventricular
  Ventricle (heart)
  In the heart, a ventricle is one of two large chambers that collect and expel blood received from an atrium towards the peripheral beds within the body and lungs. The Atria primes the Pump...
  
   size

Diagnosis

Numerous techniques are used to diagnose hypereosinophilic syndrome, of which the most important is blood testing. In HES, the eosinophil count is greater than 1.5 × 10⁹/L. On some smears the eosinophils may appear normal in appearance, but morphologic abnormalities, such as a lowering of granule numbers and size, can be observed. Roughly 50% of patients with HES also have anaemia.

Secondly, various imaging and diagnostic technological methods are utilised to detect defects to the heart and other organs, such as valvular dysfunction and arrhythmias by usage of echocardiography

Echocardiography

An echocardiogram, often referred to in the medical community as a cardiac ECHO or simply an ECHO, is a sonogram of the heart . Also known as a cardiac ultrasound, it uses standard ultrasound techniques to image two-dimensional slices of the heart...

. Chest radiographs may indicate pleural effusions and/or fibrosis

Fibrosis

Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...

, and neurological tests such as CT scans can show strokes and increased cerebrospinal fluid

Cerebrospinal fluid

Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

 pressure.

A proportion of patients have a mutation involving the PDGFRA

PDGFRA

Alpha-type platelet-derived growth factor receptor is a protein that in humans is encoded by the PDGFRA gene.-Interactions:PDGFRA has been shown to interact with PDGFRB, PLCG1, Sodium-hydrogen antiporter 3 regulator 1, Cbl gene, CRK, Caveolin 1 and PDGFC.-Further reading:...

and FIP1L1

FIP1L1

Pre-mRNA 3'-end-processing factor FIP1 is a protein that in humans is encoded by the FIP1L1 gene.-Further reading:...

genes on the fourth chromosome

Chromosome 4 (human)

125px|rightChromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 4 spans more than 186 million base pairs and represents between 6 and 6.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area...

, leading to a tyrosine kinase

Tyrosine kinase

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....

 fusion protein

Fusion protein

Fusion proteins or chimeric proteins are proteins created through the joining of two or more genes which originally coded for separate proteins. Translation of this fusion gene results in a single polypeptide with functional properties derived from each of the original proteins...

. Testing for this mutation is now routine practice, as its presence indicates response to imatinib

Imatinib

Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...

, a tyrosine kinase inhibitor.

Treatment

Treatment primarily consists of reducing eosinophil levels and preventing further damage to organs. Corticosteroids, such as Prednisone

Prednisone

Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...

, are good for reducing eosinophil levels and antineoplastics are useful for slowing eosinophil production. Surgical therapy is rarely utilised, however splenectomy

Splenectomy

A splenectomy is a surgical procedure that partially or completely removes the spleen.-Indications:The spleen, similar in structure to a large lymph node, acts as a blood filter. Current knowledge of its purpose includes the removal of old red blood cells and platelets, and the detection and fight...

 can reduce the pain due to spleen

Spleen

The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...

 enlargement. If damage to the heart (in particular the valves

Heart valve

A heart valve normally allows blood flow in only one direction through the heart. The four valves commonly represented in a mammalian heart determine the pathway of blood flow through the heart...

), then prosthetic valves can replace the current organic ones. Follow-up care is vital for the survival of the patient, as such the patient should be checked for any signs of deterioration regularly. After promising results in drug trials (95% efficiency in reducing blood eosinophil count to acceptable levels) it is hoped that in the future hypereosinophilic syndrome, and diseases related to eosinophils such as asthma

Asthma

Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

 and Churg-Strauss syndrome

Churg-Strauss syndrome

Churg–Strauss syndrome is a medium and small vessel autoimmune vasculitis, leading to necrosis. It involves mainly the blood vessels of the lungs , gastrointestinal system, and peripheral nerves, but also affects the heart, skin and kidneys. It is a rare disease that is non-inheritable and...

, may be treated with the monoclonal antibody Mepolizumab currently being developed to treat the disease. If this becomes successful, it may be possible for corticosteroids to be eradicated and thus reduce the amount of side effects encountered.

Epidemiology

HES is very rare, with only 50 cases being noted and followed up in the United States between 1971 and 1982, corresponding roughly to a prevalence of 1 to 2 per million people. The disease is even more uncommon within the paediatric population.

Patients who lack chronic heart failure and those who respond well to Prednisone or a similar drug have a good prognosis

Prognosis

Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...

. However, the mortality rate rises in patients with anaemia, chromosomal

Chromosome

A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

abnormalities or a very high white blood cell count.