Frequently Asked Questions

• What is an eosinophil?

• Where is the eosinophil found?

• What about increased blood eosinophil count (Hypereosinophilia)?

• What causes an elevated eosinophil count?

• What is Idiopathic Hypereosinophilic Syndrome?

• Sometimes eosinophils are only found in one part of the body.  What does this mean?

• What tests are done in patients with high eosinophil counts?

• Can I pass this condition on  to any member of my family?

• What is Familial Hypereosinophila?

• Tell me more about Idiopathic hypereosinophilic syndrome (HES).

• What causes hypereosinophilic syndrome?

• What is the  damage caused by eosinophils?

• How is Persistent Eosinophilia Managed?

• What Agents are used in the Treatment of HES?

• What is an eosinophil?

  An eosinophil is a type of white blood cell, which is produced from the bone marrow.  It has many granules in it which when released can fight infections.  The eosinophil count in the blood is normally 0.4 x 10 ⁹/L (0.1 - 0.6) and results from a balance between production of eosinophils from the bone marrow and  escape of eosinophils into the blood circulation.

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• Where is the eosinophil found?

  Eosinophils are only a small minority of  the white cells in the blood.

  In normal  people  most eosinophils are found in the tissues of the lung and gastro-intestinal tract  Blood eosinophil counts are normally 0.4 x 10 ⁹/L (0.1 – 0.6) ⁹/L.

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• What about increased blood eosinophil count (Hypereosinophilia)?

  An elevated blood eosinophil count may be associated with a number of reactive conditions and with disorders of the bone marrow. When the blood eosinophil count is between 0.6 to 1.5 x 10 ⁹/L you are classified as having a mild eosinophilia, moderate, when the blood eosinophil count is between  1.5 to 5 x 10 ⁹/L and severe, when the blood eosinophil count is > 5 x 10   When the blood eosinophil count is persistently greater than 1.5 x 10⁹ /L for a period of six months and damage to other parts of the body is seen eg- the heart, lungs, skin, joints and nervous system then, in the absence of any  reactive cause for the eosinophilia or a bone marrow disorder causing the eosinophilia, the term idiopathic hypereosinophilic syndrome (HES) is used.  This term  is therefore used to describe patients with  an eosinophil count above 1.5 x 10 ⁹/L with no apparent cause for the eosinophilia and in which damage to organs such as the heart and lungs was present.

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• What causes an elevated eosinophil count?

  Eosinophilic disorders may be a reaction to some abnormal process in the body (Reactive eosinophilias) or due to a cancerous/malignant process (Clonal eosinophilic disorders including eosinophil leukaemias).

  The three causes of high blood eosinophil counts (eosinophilia) are: 

  • Reactive (non-clonal) eosinophilia:

  Infections, parasitic infestations, asthma and allergies, respiratory diseases, cytokine infusions, vasculitides, non-haematological malignant diseases, drug reactions and  connective tissue diseases.

  Hodgkin's and non-Hodgkin's lymphomas are included here because the eosinophils have not been shown to be clonal although the diseases themselves are cancerous. 

   

  • Clonal Disorders associated with eosinophilia:

  Acute and chronic eosinophilic leukaemia, chronic myeloid leukaemia, polycythaemia rubra vera, essential thrombocythaemia, acute myeloid leukaemia. Chromosome 16 variants, the 8p11 myeloproliferative syndrome (EMS) and T lymphoblastic lymphoma with eosinophilia, acute lymphoblastic leukaemia, myelodysplastic disorders (MDS) with eosinophilia, systemic mastocytosis and acute lymphoblastic leukaemia.

  The distinction of clonal eosinophilia is vital for the management of patients because the clonal eosinophilic disorders in younger patients are potentially curable, for example by bone marrow or stem cell transplantation.

   

  • HES or Idiopathic Hypereosinophilia

  After exclusion of the above two categories, cases of persistent, unexplained eosinophilia fall into the category of  HES. In some of these patients a new genetic test can identify a gene that responds to treatment with a tablet(Tyrosine kinase inhibitor/imatinib)

   

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This is called single organ  eosinophil infiltration In some people eosinophils only infiltrate a single part of the body. The cause for this is unclear

Sometimes, in the absence of a high eosinophil count in the blood ( blood eosinophilia), eosinophils accumulate in specific organs, causing damage.  Examples of these are:

Eosinophilic cellulitis (Well's Disease)

Eosinophilic pneumonias (Löeffler's syndrome),

Eosinophilic fasciitis (Shulman's syndrome),

Eosinophilic pancreatitis ,

Eosinophilic synovitis ,

Eosinophilic oesophagitis^),

Eosinophilic ascites and

Eosinophilic gastroenteritis.

In these conditions, patients are observed and tests may be done to identify whether eosinophils are at any other sites and are causing damage.   Very rarely in some of these patients, HES  can develop.

Tests which identify the cause for the eosinophilia such as parasitic infections, neoplasms etc.  These are –a full blood count, biochemistry, serological tests, ECG, lung function, chest and abdominal CT scans.

Cytogenetic analysis and presence of various genes including the FIP1L1- PDGFRA gene, BCR-ABL and TEL- PDGFRB gene,  immunophenotyping of T cells,

T-cell-receptor gene rearrangements,

Bone marrow aspiration

Bone marrow trephine biopsy

B12 levels

IgE and IgM

No this disease cannot be passed to any  other member of the family like your children however familial increased blood eosinophils has been described

Marked  blood eosinophilia  has been seen in a few families in which genetic abnormalities on chromosome 5 have been found.  In these cases there have not been any damage to the organs. In some of these patients after many years, of high eosinophil counts, some will go on to develop end organ damage.

 In most cases of high blood eosinophil counts, the condition is not transmitted to any other family member.  The cause for this is unknown but it is thought to be an acquired damage to the genetic makeup of the individual.

The idiopathic hypereosinophilic syndrome by definition excludes all cases of  eosinophilia in which a cause can be found for the eosinophilia. Once clonal and reactive eosinophilic disorders are excluded, patients with prolonged eosinophilia must also have evidence of organ damage . Patients who do not have end-organ damage do, have HES, but will need continued regular search for the presence of end-organ damage  and for evidence of clonality. 

There are cases in which, after extensive search for a cause for the eosinophilia, no cause can be found by conventional techniques.

Patients with otherwise unexplained eosinophilia associated with a  T cells that secrete substances that stimulate eosinophils in the blood may be thought to have a low grade type of lymphomatous condition. This is not however treated  like a conventional lymphoma

The activated eosinophils in the hypereosinophilic syndrome cause damage to various organs through release of eosinophil granule contents.

These eosinophil  granule proteins which are known to cause death of cells, can produce clots( thrombosis), can cause  damage to the lining of  blood vessels or be neurotoxic –cause damage to nerves and thus lead to many effects on the body.   Various proteins found in the  eosinophils cause damage to the body when released from the eosinophil. It is release of these granule proteins after infiltration of tissues and thrombosis that together lead to eosinophilic end-organ damage.

Heart disease is the major cause of death. In the heart, production of eosinophil peroxidases and eosinophilic infiltration can produce constrictive pericarditis, fibroplastic endocarditis  endomyocardial fibrosis ,myocarditis, and clot formation. Your doctor will look for all of these by various tests.

In the nervous system , mononeuritis multiplex, EDN-related peripheral neuropathy ,and paraparesis⁾ have  also occurred. Please report any symptoms of numbness tingling or loss of sensation if you develop them. Central nervous system (CNS) dysfunction, cerebellar involvement,  recurrent subacute encephalopathy, epilepsy, cerebral infarction and dementia , bilateral papilloedema and eosinophilic meningitis have all been reported. Please report any symptoms  which concern you to your specialist 

Lung disease- Pulmonary infiltrates and fibrosis  ,pleural effusions and pulmonary emboli can occur. Report symptoms of breathing problems to your specialist

Skin manifestations include angioedema^), urticaria ,papulonodular lesions, multiple erythematous indurated plaques and recurrent incapacitating mucosal ulceration.

Urticaria per se and vesicobullous  can be seen

Gastrointestinal manifestations include ascites diarrhoea ,gastritis colitis⁾, pancreatitis, cholangitis and hepatitis . These will be evaluated by your specialist.

Damage to joints -Changes reported in the joints include  arthralgia effusions, destructive joint lesions and bursitis ,  and polyarthritis .Please report any symptoms of pain or swelling in your joints.

The management of patients with persistent eosinophilia is determined by its cause.   When no cause is found and a clonal bone marrow disorder has not been found, evidence of damage to end-organs should be sought.  In the presence of end-organ damage and persistent unexplained eosinophilia of greater than 6 months duration a diagnosis of HES is made.  

The treatment of hypereosinophilia, whether due to HES or clonal eosinophilia, is aimed at

1. Lowering the eosinophil count and
2. Improving symptoms produced by eosinophilic end-organ damage.
3. Treating the cause. 

Current practice

In patients who have the genetic abnormality fip1l1-pdgfra  gene  STI 571 (Imatinib) is encouraging in the treatment of carefully selected patients.  Most patients  started on 400 mg daily will  have a precipitous drop in their blood counts and therefore most people start on hundred milligrams daily, and cautiously increase the dose.  Side effects are insignificant at this dose and liver function tests could be monitored as the dose is increased.  The response rate is 100%, but no one knows whether patients with persistent unexplained eosinophilia with no cause and an as yet undetected gene will also respond.  The clinical response is rapid with eosinophil counts returning to normal within a week of starting treatment.

When cardiac or lung damage is present steroids may reduce fibrosis and prevent thrombotic events.

Previous practice

Prednisolone was the drug of choice before imatinib was discovered and can reduce eosinophil infiltration.  Steroids (1mg/kg/day) will reduce the effects of release of eosinophil granule contents, reduce blood eosinophilia and suppress inflammation.

 HES often responds well to treatment with agents that decrease T-cell production  if the HES is due to the  presence of abnormal T-cells. Agents such as cyclosporin are therefore useful in cases of HES in which T- cell driven eosinophilia is present.  Hydroxyurea can be used for steroid-resistant patients in a dose of 1 to 2g/day.   The use of vincristine chlorambucil and etoposide should be restricted to cases in which persistent non-responsive end-organ damage is occurring  and the patient is refractory (does not respond  to imatinib) because they carry a small risk of inducing MDS and secondary leukaemia. Alpha  interferon (a IFN) has been shown to produce benefit in steroid-resistant cases. Patients with HES who have a benign clinical course will respond to simple treatments.  In the presence of progressive disease, allogeneic stem cell transplantation should be carried out with either bone marrow from an allogeneic or unrelated donor or using peripheral blood stem cells.