In clinical practice there are diseases and conditions under which
of eosinophils in peripheral blood and tissues increases
(eosinophilia). Increasing the number of eosinophils ofmorethan 1500 cells / mm referred to
hypereosinophilia.
eosinophil as a separate element of the cell is described for the first time Paul
Ehrlich in 1879 That he used sour eosin stain, named after the Greek goddess
dawn, for the histological staining of blood and tissues.
Ehrlich showed that eosinophils are from 1 to 3% of peripheral leukocytes
levels in healthy individuals.
Over the next 40 years, has accumulated a lot of information about the
eosinophils: increased number of cells was associated with bronchial asthma (BA) and
intestinal parasites infestation. Also the number of eosinophils significantly increased in tissues
animals after an anaphylactic reaction. This suggested that eosinophils provide
hypersensitivity anaphylaxis. This hypothesis
remained the main explanation for the function of eosinophils from the beginning of the century up until the 1980
years [1]. In 1950 "s of the function of eosinophils was so little known that their
presumably attributed to the ancestors of red blood cells [2].
Morphology of eosinophils
When light-optical study of the diameter of eosinophils is
12-17 microns and are usually somewhat larger than neutrophils. In contrast to mature
polymorphonuclear leukocytes (PMNL), whose kernels have about four lobes,
nucleus of eosinophils, usually consist of two lobes connected by
thread. The main peculiarity of their cytoplasm is the presence of two types
specific granules (large and small) that have red or orange
[3]. Even in poorly stained smears can be distinguished from the granules of neutrophils, so
as they aremorenumerous and distinctly larger. Large granules contain
basic proteins that are unique to eosinophils.
These include: a large core protein (BOP), eosinophilic cationic protein
(EPC) , eosinophilic peroxidase (EPO), eosinophil neurotoxin
(AHD), formerly called eosinophilic protein X, and a homologue of BCS [1].
Small granules contain enzymes arylsulfatase B and acid phosphatase, also
found in azurophilic granules of neutrophils [4]. Lizofosfolipaza In
(Charcot-Leyden crystals) - an enzyme membrane of eosinophils - does not play an important role in the pathogenesis of
disease and has no diagnostic value.
in activated eosinophils number of grains
significantly reduced and cells are often vacuolating, becoming less dense than
nonactivated eosinophils [5].
Options eosinophils
functions of eosinophils is unknown. They have many other functions
circulating phagocytes such as monocytes and PMNL. Although
eosinophils are capable of phagocytosis, they destroy the bacteria inside them
less efficiently than neutrophils.
direct evidence that eosinophils kill parasites
in vivo, No, but they are toxic to helminths in vitro , and helminthiasis
often accompanied by eosinophilia [1]. Eosinophils may modulate the reaction
immediate hypersensitivity by inactivating mediators released
mast cells (histamine, leukotrienes, lysophospholipids and heparin).
BOP and EPC are toxic to some parasites and cells
mammals. AHD can seriously damage the myelin nerve fibers. BOP and EPC
bind heparin and neutralize its anticoagulant activity. EPO
presence of hydrogen peroxide and halogen generates oxidative radicals [6].
Prolonged eosinophilia sometimes leads to tissue damage, the mechanisms which
not yet clear. The extent of damage related to eosinophilic infiltration of tissues,
duration of eosinophilia and the degree of activation of eosinophils [7]. The greatest
damaging effect of eosinophils found in states such as disease
Leffler (fibroplastichesky eosinophilic endocarditis) and idiopathic
gipereozinofilnomu syndrome [2].
kinetics of eosinophils
Eosinophils - a nondividing granulocytes, which, like Other
PMNL, continuously produced in the bone marrow from a single stem cell.
Eozinofilopoez and differentiation of eosinophils from progenitor cells
regulate T cells through secretion of granulocyte colony-stimulating factor and macrophage
(GM! CSF), interleukin-3 (IL-3) and IL! 5 [8, 9 ]. In addition, IL-5 and GM
! CSF activate eosinophils by inducing the transition of cells from normal density in
low (less than 1.085) [10].
lifespan of eosinophils is 10-12 days.
leaving the bone marrow, where they are produced and ripen in 3-4 days,
eosinophils few hours circulate in the blood (the period of their half-life is
6-12 h). Then, like neutrophils, they leave the bloodstream and go to
perivascular tissue, mainly in the lungs, gastrointestinal tract and
skin, where they remain for 10-14 days. For each peripheral eosinophil
blood accounted for about 200-300 of eosinophils in bone marrow and 100-200 in other
tissues [11].
Eosinophils in normal smear blood ranged from 1 to 5%
leukocytes. In absolute figures, accepted as the norm 120-350 eosinophils in 1 mm
(120-350. 106 / l) in peripheral blood. Level from 500 to 1500 eosinophils / mm
seen as an easy eosinophilia, andmorethan 1500 cells / mm - as
hypereosinophilia: moderate (1500-5000 cells / ml) and severe (more than 5000
cells / ml) .
absolute number of eosinophils in the peripheral blood of healthy people
varies. Diurnal fluctuations in the number of eosinophils are inversely
depending on the level of cortisol in plasma, and the maximum occurs at night
hours, but at least - in the morning [12].
Causes of eosinophilia
eosinophiliamorethan 5000 cells / mm occurs rare. Some
patients with leukocytosis above 100,000 cells / ml 75% of cells can be
eosinophils. Gipereozinofilnyh number of states is limited. These include:
parasitic infestations, neoplasms (acute myelogenous leukemia, acute lymphoblastic leukemia
, eosinophilic leukemia), the response to toxins (toxic syndrome
oil), eosinophilia-myalgia syndrome (receiving L-tryptophan), idiopathic
gipereozinofilny syndrome (IGES), periarteritis nodosa.
Causes moderate eosinophilia know a lot. The increased number of eosinophils
in peripheral blood dermatologists often find a
patients with skin rash and pulmonologists - in connection with pulmonary infiltrates and
allergic reactions. The most common cause of eosinophilia in children are
parasitic infestation, and in adults - dasg reaction [13].
major causes of eosinophilia are presented in Table. 1.
Table 1. The main causes of eosinophilia
Allergic diseases
most common cause of eosinophilia - an allergic disease,
primarily respiratory diseases and skin. Asthma - a chronic inflammatory disease
characterized peripheral blood eosinophilia,
bronchial tissue and sputum [14, 15]. The content of eosinophils in the blood of patients with asthma
varies and rarelymorethan 500-1000 cells / ml.
Comparison of different forms of asthma shows that the number of eosinophils in atopic
the form of higher than non-atopic, and even higher in patients with aspirin
asthma [16]. In patients without symptoms, especially
receiving basic treatment glucocorticosteroids (GCS), the number of eosinophils often
normal [17].
patients with severe exacerbations of asthma was noted eosinopenia,
associated with the migration of eosinophils into the respiratory tract that involves
deterioration of lung function and a parallel increase in the concentration of ECP in seasm
[18]. Study of biopsy samples taken from patients with bronchial asthma during an attack or
shortly after, also showed significant eosinophilia [4].
parasitic
Eosinophilia can cause almost any parasitic infestation
tissues, are usually the exception and non-invasive protozoan metazoynye
agents [19]. The most common cause of hypereosinophilia - toxocarosis,
caused by invasive larvae of nematodes Toxocara canis and T. cati ,
are common intestinal parasites of dogs and cats in the internal organs
man with a long-term follow their migration through the body.
Typical symptoms are fever, cough, wheeze in the lungs (pneumonitis),
hepatosplenomegaly, generalized lymphadenopathy, skin rashes, and (rarely)
pseudotumor eyes.
Leukemia
rare cause of hypereosinophilia (usually children) can be
eosinophilic leukemia. It is manifested symptoms of acute myeloid leukemia;
feature - the rapid development of heart failure due to damage
endocardium and heart valves. Treatment options include hydroxyurea, and vincristine
. If it affects the heart valves shown surgical treatment [2]. In
quarter of patients with Hodgkin hypereosinophilia found that,
may be associated with increased levels of IL-5, the majority of patients improved and
level of IgE [22].
Idiopathic gipereozinofilny syndrome
IGES - a rare condition of unknown etiology, first described in 1968
To this end, the syndrome is characterized by three features: the continuing no less than 6 months
hypereosinophilia peripheral blood (more than 1500 cells / ml), no
other causes of eosinophilia, changes in organs or their functions, which are directly associated with eosinophilia
or find another explanation [2]. Mostly
ill men over 30 years. Eosinophilia in rare cases can reach 50,000
cells / ml.
Characteristic skin lesions (rash), brain (seizures),
heart (endokarditichesky fibroelastoz) and liver (hepatitis). In the absence of
treatment may develop restrictive heart failure. Treatment of GCS,
vincristine, hydroxyurea, and. "Interferon can slow the progression of the disease
[21].
Uzelkov periarteritis
This disease is characterized by segmental inflammation and necrosis
medium arteries of muscular type. Often ill men
middle age. In early disease the most common fever, abdominal pain,
symptoms of multiple mononevrita, skin rash, fatigue, weight loss, arthralgia
and kidney failure. In the analysis of blood - leukocytosis to 20000-40000 cells / ml,
increase in seasm immunoglobulins, often proteinuria and hematuria. Although
usually neutrophilic leukocytosis, in some patientsmorethan 50% of leukocytes
are mature eosinophils. The diagnosis is made only in identifying signs of necrotizing vasculitis
in biopsy tissue of the typical areas of damage
during acute inflammation. SCS and the immunosuppressive treatment prevents
progression of the disease and can cause a remission [2].
exposure to toxins
Over the past 20 years there have been two major epidemics. In
1981 in Spain was an outbreak of the so-called toxic oil syndrome
. The source of the epidemic was eating
intended for industrial use of rapeseed oil, which was labeled as olive
[23]. Ill about 20 thousand people,
mortality wasmorethan 1,5%. At the early stage of the disease was manifested with fever,
cough, skin rash, myalgia and eosinophilia to 20000 cells / ml, at a later stage
- swelling of limbs, sklerodermopodobnymi skin changes,
polyneuropathy, muscular weakness and flexion contractures of the [ 24].
eosinophilia-myalgia syndrome was first described in 1989 patients,
long taking large doses of L-tryptophan as a sedative
means [ 25]. The patients, along with generalized myalgia and eosinophiliamore
1000 cells / ml was noted lung damage, manifested
nonproductive cough, shortness of breath and chest pain. X-ray examination found
bilateral pulmonary infiltrates, sometimes pleural effusion.
Treatment SCS led to a rapid relief of clinical manifestations of syndrome of eosinophilia-myalgia
and normalization of the level of eosinophils [24].
Eosinophilic pulmonary infiltrates
Eosinophilic infiltrates the lungs, or eosinophilic pneumonia,
cover several pathological states of different aetiology, for which
characterized by eosinophilic infiltration of the lungs and usually peripheral blood eosinophilia
.
Simple pulmonary eosinophilia was first described in 1932 by Leffler
reasons unknown to her. Characterized by volatile pulmonary infiltrates, accompanied by
low-grade fever, minimal respiratory failure, moderate
eosinophilia of peripheral blood and the rapid spontaneous resolution [26].
Chronic eosinophilic pneumonia has features of systemic
disease, with cough, shortness of breath, fever, weight loss, anemia,
hepatomegaly and diffuse lymphadenopathy. Mostly
ill women over 30 years.
characterized by high peripheral blood eosinophilia, an increase in the number of PMNL
, a small elevation of IgE. X-rays - one-and two-way
shadows, which are located in the tops of the lungs and the periphery.
Biopsy revealed pulmonary eosinophilia without accompanying
arteritis. GCS treatment gives good results, although after their withdrawal infiltrates
again may appear [27].
Allergic bronchopulmonary aspergillosis (Abla) is one of the most frequent causes of
eosinophilic pneumonia in patients with asthma. To clarify the diagnosis
necessary staging of cutaneous prick-test with Aspergillus fumigatus .
Number of eosinophils in the blood are usually higher than 1000 cells / ml, simultaneously with the appearance of
transient infiltrates, detected by X-ray light,
eosinophilia becomesmorethan 2000 cells / uL. The level of total IgE and specific
IgE to A. fumigatus is very high. Also for Abla characterized
peculiar type of central bronchiectasis. Treatment for the SCS and other
antiasthmatic dasgs. The success of treatment and prognosis
evaluated over the continuous drop in the level of seasm IgE [21]. Lung lesions
other fungi ( Candida albicans, Curvularia lunata, Dreschlera hawaiiensis )
rarely combined with eosinophilic pulmonary infiltrates [28].
tropical pulmonary eosinophilia caused by microfilariae,
which usually do not find in the blood. There is a persistent eosinophilia,
which can reach 50,000 cells / ml, with a simultaneous rise of IgE levels and
high titer antibodies antifilyariynyh [29].
Allergic granulomatosis, syndrome or Churg-Strauss, is described in
1951 and includes severe asthma with hypereosinophilia, eosinophilic infiltrates,
necrotizing eosinophilic vasculitis and granulomas in various organs
[30].
Men and women are sick with the same frequency. Asthma is often preceded by
vasculitis. The number of eosinophils in the peripheral blood increased from
1500 to 30,000 cells / ml (10%) are often elevated levels of seasm IgE.
Treatment for highdoses of corticosteroids (30-80 mg / day), with resistance to
which shows the appointment of azathioprine [31, 32].
Dasg eosinophilia
Drinking a lot of dasgs can lead to the development
moderate eosinophilia. Eosinophilic dasg reaction can
asymptomatic and be the only manifestation of hypersensitivity to the dasg
or combined with various syndromes: interstitial nephritis,
fever, skin rash, lymphadenopathy, hepatosplenomegaly, arthritis,
Stevens-Johnson syndrome. The main groups of dasgs, receiving
which may lead to eosinophilia are listed in Table. 2.
Table 2. Dasgs lead to eosinophilia
most common cause of antibiotic, antimicrobial
means, cytostatics , NSAIDs and psychotropic dasgs [21]. 7-10 days after discontinuation
eosinophil counts normalized [2]. So,
clinical, diagnostic, therapeutic, and prognostic features of various
pulmonary eosinophilia differ significantly. For the ultimate understanding of these disorders
further research is needed.