Hypereosinophilic syndrome

1 - WHAT IS THE EOSINOPHILIC SYNDROME?

Eosinophils are circulating blood cells which belong to the family of leucocytes (white blood cells). They are present in everyone at low levels (< 0.5 x 10⁹/L of blood). The term moderate eosinophilia is used for levels of between 0.5 and 1.5 x 10⁹/L and a rise beyond 1.5 x 10⁹/L is defined as hypereosinophilia. Hypereosinophilia in blood and/or organs requires a methodological approach with investigations carried out according to the clinical history, clinical examination and laboratory assessment. Alongside allergic or drug-induced causes, which are the most common causes, hypereosinophilia is seen in various diseases (immune system disease, blood dyscrasias or cancers). When an exhaustive clinical enquiry remains negative, the assumption of hypereosinophilic syndrome (HES) must be considered. This is a rare disease which may affect men or women at any age.

2 - WHAT ARE THE SYMPTOMS?

When present in blood, eosinophils may or may not infiltrate all tissues and/or organs. It is reported that many patients may have chronic asymptomatic hypereosinophilia, i.e., eosinophilia with no organ involvement. The organs and tissues most commonly involved are the skin, lungs and gastrointestinal tract. Involvement of the nervous system and heart is more serious but is only found in 20% of patients. Dermatological features are common and very variable and include pruritus, skin rash, nodules, mucosal ulcerations and oedema. The gastrointestinal involvement may cause abdominal pain, diarrhoea or ascites (a liquid effusion in the abdominal cavity resulting in an increase in abdominal girth). Chronic cough, asthma, breathlessness and abnormalities which can be detected on a chest radiograph or CT of the lungs indicate respiratory involvement.

3 - HOW IS THE DIAGNOSIS MADE?

The diagnosis is based on confirmation of an increase in eosinophils on at least 2 occasions in a blood sample.

Organ involvement, particularly cardiac, must then be investigated, for which occasionally requires an organ biopsy (colon, stomach or skin) to confirm the presence of eosinophils in the tissues. 

The cause of the hypereosinophilia must also be investigated. Once the usual causes have been excluded (medications, parasites, cancers and immune system diseases) more detailed investigations in a specialised unit are performed to confirm the hypereosinophilic syndrome. These investigations help to identify various forms of HES, which are treated differently. The so-called neoplastic HES (or clonal or primary) are due to abnormalities of eosinophil production in the bone marrow. The reactive (or secondary or occasionally known as lymphoid) HES are due to increased stimulation of eosinophils usually produced by the bone marrow. The term idiopathic hypereosinophilia is used when it is not possible to distinguish between neoplastic or reactive HES. In most cases the HES are chronic diseases which require long term management.

4 - HOW TO TREAT THEM?

In unexplained hypereosinophilia situations with no organ involvement, after ensuring that no cardiac involvement is present, simple monitoring with blood samples (and the eosinophil count) without treatment is usually proposed.

Medications such as imatinib may be remarkably effective in the so-called “clonal” hypereosinophilic syndromes. In most other situations treatment with corticosteroids is usually effective (at least initially). If the hypereosinophilia persists, despite corticosteroids or recurs after improvement on corticosteroid therapy, the so-called 2^nd line treatments are then offered such as interferon-alpha or hydroxyurea. New treatments more specifically targeting eosinophils are currently being developed and may help to avoid the tolerability problems of the usual treatments.

Further information about HES is available on the CEREO site.

Hypereosinophilia syndrome reference centre in France: www.cereo.fr.