What is Hypereosinophilic Syndrome: Types, Symptoms, Treatment, Diagnosis

Hypereosinophilic syndrome is a medical condition where there is an abnormally high blood eosinophil count. The high blood eosinophil remains for over six months and has no identifiable cause. Hypereosinophilic syndrome is also associated with multiple organ damage and is categorized as a myeloproliferative disorder (MPD). Body systems usually involved in hypereosinophilic syndrome include the nervous system, heart or the bone marrow. This condition is known to be associated with chronic eosinophilic leukemia due to certain similar characteristics and genetic defects. The disease may occur as multiple manifestations or even individually as well. Generally the onset of hypereosinophilic syndrome is subtle, but it can also occur in a dramatically sudden manner and involve cardiac, thrombotic or neurotic complications. While any organ system can be involved in hypereosinophilic syndrome, it usually affects the skin, heart, central nervous system (CNS), and the respiratory tract. Originally, the cause of hypereosinophilic syndrome was not known, but now, advances in diagnostic technologies has made it possible for a potential underlying cause to be identified in most cases. Management of hypereosinophilic syndrome is based on the severity of the condition.

Hypereosinophilic syndrome is a disease that is characterized by extremely high blood eosinophils. This means that the body manufactures too many white blood cells in the bone marrow. Due to the large collection of white blood cells in the bone marrow, they start to spill out of the bone marrow and start accumulating in other tissues and in the blood. The diagnosis of hypereosinophilic syndrome happens when a full blood count test shows continued elevated levels of eosinophils. Hypereosinophilic syndrome is also often known as chronic hypereosinophilic leukemia. Often times, people suffering from hypereosinophilic syndrome do not display any symptoms and the disease gets diagnosed by accident during any routine blood test. Hypereosinophilic syndrome is a rare disease and the natural course of progression varies from person to person.

Hypereosinophilic syndrome is known to remain stable over many years, before suddenly progressing and transforming into acute leukemia. Due to the severity of this reason itself, appropriate treatment needs to be undertaken upon detection of hypereosinophilic syndrome.

Hypereosinophilic syndrome can generally be categorized into two types.

1. Myeloproliferative variant.
2. Lymphoproliferative variant.

Myeloproliferative Variant of Hypereosinophilic Syndrome: Patients suffering from the myeloproliferative variant of hypereosinophilic syndrome develop endomyocardial fibrosis and may sometimes also develop lymphoblastic or acute myeloid leukemia. This usually occurs in males and treatment involves giving low doses of imatinib, which is a tyrosine kinase inhibitor. Some patients suffering from the myeloproliferative variant may also develop cytogenetic changes that involves platelet derived growth factor receptor beta. The treatment protocol for these patients also remains the same, that is, imatinib.

Lymphoproliferative Variant of Hypereosinophilic Syndrome: Patients having the lymphoproliferative variant of hypereosinophilic syndrome suffer from skin abnormalities, hypergammaglobulinemia, serum sickness, etc. They are known to respond favorably to corticosteroids. In rare cases, these patients end up developing T-cell lymphoma.

Some Other Lesser Known Forms Of Hypereosinophilic Syndrome Include:

• Gleich syndrome.
• Familial hypereosinophilic syndrome.
• Hyperleukocytosis.

Patients suffering from hypereosinophilic syndrome display diverse symptoms. Symptoms primarily depend on the organs that have been affected by Hypereosinophilic Syndrome. Some of the common symptoms that a patient may present with Hypereosinophilic Syndrome include:

• Fever.
• Fatigue.
• Muscle pains.
• Dizziness.
• Mouth sores.
• Shortness of breath.
• Cough.
• Generalized itching, known as pruritus.
• Diarrhea.
• Cardiomyopathy.
• Thromboembolic disease.
• Pulmonary disease.
• Skin lesions.
• Neuropathy.
• Lower ventricular size.
• Hepatosplenomegaly.
• Atopic eczema.

Let us take a look at the more specific symptoms of hypereosinophilic syndrome.

As the cardiac system is most commonly affected in hypereosinophilic syndrome, damage to the cardiac system can become a cause of mortality. Damage to the cardiac system generally involves:

• Acute necrosis in the early stages of the disease, having no clinical manifestations. It can sometimes be severe enough to cause symptoms.
• Thrombotic stage.
• Endomyocardial fibrosis.

Symptoms for all these three stages include:

• Dyspnea or orthopnea.
• Chest pain.

Hematologic damage is characterized by generally non-specific symptoms such as fatigue, left upper quadrant pain, thrombotic episodes, etc. Pain in the upper left quadrant is an indication of splenomegaly, and around 40% patients present with it. Thrombotic episodes also occur frequently and can manifest as neurological symptoms as well. Thrombotic events can also occur due to hypercoagulability, mechanism of which remains unknown as of date.

• Thrombotic or embolic strokes or even transient ischemic strokes make occur. These are generally considered as the first-stage manifestations of hypereosinophilic syndrome.
• Many patients experience encephalopathy due to dysfunction of the central nervous system.
• Slurred speech and blurred vision.
• Peripheral neuropathies present as sensory changes, motor deficits, motor complaints, or sensory complaints.

• Pruritus.
• Angioedema.
• Dermatographism.

• Eosinophilic infiltration of the periphery and base of the lungs.
• Recurrent Angioedema.
• Chronic and persistent cough – this is one of the most common respiratory symptom associated with hypereosinophilic syndrome.
• Dyspnea.
• Pulmonary fibrosis; though this is not a common symptom.
• Infrequent bronchospasm and asthmatic symptoms.
• Rhinitis.

• Diarrhea.
• Nausea and abdominal pain.
• Small bowel necrosis may also occur sometimes in Hypereosinophilic Syndrome.
• Sclerosing cholangitis also occurs in some patients with Hypereosinophilic Syndrome.

Many of the symptoms that manifest in hypereosinophilic syndrome are common to many other medical problems. Therefore, making an initial diagnosis is difficult for doctors. The process usually begins with ruling out other conditions with similar symptoms. Conditions that need to be ruled out include:

• Allergic diseases.
• Parasitic infections.
• Cancers.
• Drug reactions.
• Autoimmune diseases.

An immunologist has specialized training for diagnosing hypereosinophilic syndrome and then working with other specialists to come up with a treatment plan. Testing include blood tests, stool evaluation for ruling out or detecting parasitic infections, allergy testing for detecting any environmental allergies or even food allergies, CT imaging of the affected organs, biopsies of the skin or affected organs, and even genetic testing to detect mutations for diagnosing and then developing a treatment protocol.

Once hypereosinophilic syndrome is diagnosed, a chest x-ray and echocardiogram are performed to assess the condition of the heart and lungs. Other commonly performed tests include:

• Liver and kidney function tests.
• Serum vitamin B12 level tests.
• Serum tryptase level tests.
• Erythrocyte sedimentation rate (ESR).

Treatment of hypereosinophilic syndrome is undertaken with the goal of lowering the level of eosinophils in the blood and tissues. This prevents further tissue damage, particularly to the heart and lungs. The standard treatment for hypereosinophilic syndrome includes glucocorticosteroid medications like prednisone. Some chemotherapeutic agents are also used, including chlorambucil, hydroxyurea and vincristine. A less common treatment that is sometimes used is interferon-alpha, and it is administered through frequent injections.

Research is ongoing on coming up with new and better treatments for hypereosinophilic syndrome. One such approach is the use of tyrosine kinase inhibitors, commonly going by the name of imatinib. Even monoclonal antibodies, such as alemtuzumab and mepolizumab, are showing promise in the treatment of hypereosinophilic syndrome.
In severe cases, hypereosinophilic syndrome may prove to be fatal.

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