Frequently Asked Questions
What is an eosinophil?
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.
Where is the eosinophil found?
are only a small minority of the white cells in the blood.
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.
increased blood eosinophil count (Hypereosinophilia)?
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
What causes an elevated
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)
parasitic infestations, asthma and allergies, respiratory diseases,
cytokine infusions, vasculitides, non-haematological malignant diseases,
drug reactions and connective tissue diseases.
non-Hodgkin's lymphomas are included here
because the eosinophils have not been
shown to be clonal although the diseases themselves are cancerous.
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.
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)
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)
pneumonias (Löeffler's syndrome),
fasciitis (Shulman's syndrome),
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
IgE and IgM
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.
cases in which, after extensive search for a cause for the eosinophilia,
no cause can be found by conventional techniques.
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
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.
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
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
Lung disease- Pulmonary infiltrates and fibrosis ,pleural effusions and
pulmonary emboli can occur. Report symptoms of breathing problems to your
manifestations include angioedema), urticaria ,papulonodular
lesions, multiple erythematous indurated plaques and recurrent
incapacitating mucosal ulceration.
per se and vesicobullous can be seen
manifestations include ascites diarrhoea ,gastritis colitis),
pancreatitis, cholangitis and hepatitis . These will be evaluated by your
-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.
of hypereosinophilia, whether due to HES or clonal eosinophilia, is aimed
eosinophil count and
symptoms produced by eosinophilic end-organ damage.
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.
or lung damage is present steroids may reduce fibrosis and prevent
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
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.