White blood cell - eosinophils - Eosinophilia
White blood cell – eosinophils – Eosinophilia


We talk hypereosinophilic when eosinophils counts greater than 500 / mm3 (5 gigas / L).

The moderate eosinophilia (500 to 1000 / mm3) are most often related to atopy (asthma, eczema …) taking a drug or a parasitic disease.

Only helminths cause eosinophilia and when stool examination is positive, eosinophilia is often in the process of normalizing (Lavier curve); in France, think first to the tænia and fluke.

Eosinophilia requires a more thorough investigation when the rate reached 1,500 / mm3.

For these values, eosinophils can cause visceral complications, through the release of cationic proteins in their granules azurophilic: Major Basic Protein (MBP),Eosinophilic Cationic Protein (ECP), neurotoxin, éosinoperoxydase.

The most common visceral complications and more serious are heart (restrictive heart disease, mitral insufficiency or tricuspid) and central neurological (headache, impaired alertness, cognitive impairment) or peripheral (sensory axonal peripheral neuropathy). The pulmonary involvement (cough, chronic eosinophilic pneumonia type Carrington) and digestive (eosinophilic gastroenteritis) are less frequent and usually corticosteroid. Mucocutaneous involvement is frequent (nodules, papules, subungual splinter haemorrhages, Raynaud’s phenomenon, mucosal ulceration).


In the presence of chronic eosinophilia (more than 1500 / mm3), the etiological investigation should follow a logical and rigorous order (summary in Box 1 at the end of the chapter).


Is there a drug intake? A major form of iatrogenic eosinophilia is the DRESS (Drug Related Eosinophilia with Systemic Symptoms); The most frequently implicated drugs are Disulone®, minocycline, the allupurinol the antiepileptic (mainly carbamazepine).

Aboriginal helminthiasis:

Will he helminthiasis? In this case, total immunoglobulin E are increased in most cases. In France, besides the fluke, it must essentially seek trichinosis (for import of infected meat) and two parasitic impasses: anisakiasis after ingestion of raw fish larva migrans syndrome (infestation by larvae of the tapeworm echinococcus dog or Toxocara canis).


Will there a rash? In this case, we must mention mastocytosis if there is urticaria pigmentosa, bullous pemphigoid if the rash has bubbles, Kimura disease if there is peripheral lymphadenopathy and ENT location and lymphomas T epidermotropic ( Sezary syndrome and mycosis fungoides) whose diagnosis is made through the study of blood smear in search of atypical lymphocytes.

Eosinophilic lung:

Will he pulmonary symptoms? Eosinophilia in itself may cause coughing (linked to the release of MBP). The association of pulmonary infiltrates and eosinophilia defines eosinophilic lung. We must then seek first drug cause (antibiotics, antimitotic, amiodarone …) or parasitic (mainly pulmonary filariasis which in France is mainly observed in patients from Pondicherry and the Comoros). Once these causes removed, attempts allergic bronchopulmonary aspergillosis (described by Pepys and Hinson): measurement of specific immunoglobulin E of aspergillosis, research hyphae in sputum or bronchoalveolar lavage.

We must also think, if there is a extrarespiratoires asthma and signs of vasculitis, allergic vasculitis with Churg-Strauss. After excluding these etiologies, if it is a woman, and if the signs are exclusively kept with a respiratory condition, it evokes chronic eosinophilic pneumonia Carrington (the scanner there is peripheral infiltrates, negative image pulmonary edema); this pneumonia Carrington is steroid-responsive.

Digestive disease:

Will he digestive symptoms? If diarrhea and / or abdominal pain, accompanied by an inflammatory biological syndrome, two conditions must be sought: Crohn’s disease, and rarely Whipple’s disease. Endoscopies, with research Tropheryma whippeli PCR (polymerase chain reaction) allow to distinguish and choose the treatment: prednisone in the first case, antibiotics (Bactrim or rifampicin) in the second case.

Systemic disease:

At least six systemic diseases may be accompanied by a major eosinophilia.

Four are vasculitis: vasculitis Churg-Strauss cited above, but also of Wegener’s granulomatosis, polyarteritis nodosa and multiple embolism of cholesterol crystals that are actually differential diagnosis of peri-arteritis nodosa.

Shulman fasciitis is constantly accompanied by eosinophilia; it is a particular form of scleroderma, often triggered by an unusual effort, which is not accompanied by Raynaud’s phenomenon and no visceral involvement, but the severity is related to the risk of aplastic anemia.

Some severe forms of rheumatoid arthritis, with episcleritis, rheumatoid nodules, vasculitis and may be accompanied by eosinophilia.

Viral Pathology:

Two viral infections should be systematically sought: chronic hepatitis related to C (HCV) viruses (but in this case eosinophilia is closer to 1000 than 1500 / mm3) and especially infection by viruses human immunodeficiency (

HIV) which can be revealed by eosinophilia.

Solid cancer:

Slow-growing cancers may progress for several months under the mask of eosinophilia.

In addition to colon cancer, stomach, uterus and lung, there has been such hypereosinophilia during malignant histiocytofibromas or sclerosing intravascular bronchioloalveolar cancers.

The positron emission tomography may help to highlight the tumor.

Hematological and immune deficiency:

Among the hematological, Hodgkin’s disease (in which eosinophilia is a poor prognostic factor) and especially T-cell lymphomas (known devices according to their histology) can be revealed by eosinophilia. Ganglion or muscle biopsy can help diagnose; HTLV-1 virus serology should be systematic.

Hypereosinophilic syndrome:

When this comprehensive investigation is negative, it is called hypereosinophilic syndrome whose criteria have been defined by Chusid in 1975:

– Major hypereosinophilia (> 1500 / mm3) and chronic (more than 6 months);

– Visceral involvement (discussed above);

– No cause found (but we saw that we can ignore for many years a strong T-cell lymphoma or cancer).

Three possibilities are possible.

Myeloproliferative disorder:

It is in 30% of cases, with myeloproliferative disease because there splenomegaly (while the liver is normal) a significant increase in vitaminémie B12 and serum tryptase, myelofibrosis in bone marrow biopsy. The practice of a classical medullary karyotype is very rarely contributory but molecular biology allowed Cools in 2003 to highlight a fusion transcript called FIP1L1-PDGFRA. This transcript is associated with a deletion in chromosome 4 to approximate the FIP1L1 molecule of a gene encoding receptor alpha platelet derived growth factor (PDGF).

The latter molecule has a tyrosine kinase activity.

The fusion transcript broadens the context of myeloproliferative original hypereosinophilia which currently represent approximately 30% of unexplained prolonged hypereosinophilia. The discovery of Gleevec that has antityrosine kinase activity has transformed the prognosis of these patients. He is active at a dose of 100 mg / day, or even less.

Variant lymphoid hypereosinophilic syndrome:

This is a variant of lymphocytic hypereosinophilic syndrome because lymphocyte phenotyping highlights an aberrant phenotype, usually a CD3 T CD4 + population that has a TH2 activity. It is known that Th2 cells secrete IL-5 (which is the main cytokine regulating the growth of eosinophils) and IL4 which explains the frequency of the increase in E immunoglobulins in these patients.

In half the cases, the study of clonal T receiver confirms the nature of these aberrant T cells. Patients usually have a single clonal expansion of their TH2 lymphocytes; they rarely progress to a classic T-cell lymphoma. The variant lymphoid one third unexplained prolonged hypereosinophilia.

The treatment of these T cell clonal expansions relies initially on prednisone, and when glucocorticoid on a novel monoclonal antibody directed against interleukin 5 (mepolizumab).

This antibody is administered as an infusion of about 4 hours at a dose of 10 mg / kg. It is active for 10 to 16 weeks.

Idiopathic hypereosinophilic syndrome:

There is no argument in favor of a myeloid or lymphoid origin hypereosinophilic syndrome (which is the case for about 35% of patients). In this case we must periodically seek cancer or lymphoma T.

The treatment is indicated in cases of visceral complications (heart disease, eosinophilic gastroenteritis, central neurological disorders, sensory axonal neuropathy …) or at least in case of anomaly additional examinations (electrocardiography, echocardiography, MRI, electromyogram). It is based primarily on the prednisone dose of 0.5 mg / kg and when glucocorticoid on the addition of mepolizumab every 2 to 4 months.

Box 1. Summary: major cause of chronic non-parasitic eosinophilias higher than 1500 / microL
Iatrogenic causes
β-lactam antibiotics Isoniazid
Amphotericin B
And drug officials DRESS syndrome
Indigenous helminths
Larva migrans
Bullous pemphigoid
Systemic mastocytosis
Kimura’s disease
Mycosis fungoides, Sezary
Eosinophilic lung
Parasites (filariasis, larva migrans)
Hinson Pepys (aspergillosis)
Vasculitis Churg-Strauss
Pneumonia Carrington
Digestive disorders
Tissue disorders
Rheumatoid arthritis
Polyarteritis nodosa
Cholesterol embolism
Viral diseases
Solid cancers
Blood diseases and immune deficiencies
B-cell lymphomas
T-cell lymphomas
Hypereosinophilic syndromes