Eosinophils and Diseases Associated with Eosinophils.
PKGhatak, MD
Eosinophils are white blood cells belong to granulocytes, other members of this group are Basophils and Neutrophils (also called polymorphs). The name, granulocyte is derived from the presence of granules in the cell cytoplasm. The granules of eosinophils are coarse and turn red when stained with Eosin due to the presence of amino acids arginine and lysine in the protein which reacts with Bromine in Eosin. The eosinophils are important Innate Immunocytes, involved in protecting the body from multicellular parasites, fungi and some viruses and are important determinants in certain diseases.
The easily identifiable feature of the eosinophils is their special characteristic Bilobed nucleus.
Formation and distribution of Eosinophils.
The Hematopoietic stem cells of the bone marrow are the source of eosinophils; and in about 7 days the mature eosinophils leave the bone marrow. Most of them head for the thymus gland, spleen, lymph nodes, GI tract and the rest of the organs with the exception of the esophagus, ovaries, and uterus. Under normal health conditions, the eosinophils are not present in the Esophagus and Lungs and only a few eosinophils are present in the skin.
The Thymic Th2 cells initiate eosinophil production by secreting IL-5. (Interleukin-5).
Normal blood eosinophil count is 3 to 8 % and the total maximum count is 500 per microliter. In the peripheral blood, the eosinophils live about 1/2 days and in the tissues, they survive 8 days.
A total eosinophil count of 800 / microliter is abnormal and called hypereosinophilia, a count over 1,500 per microliter is called Hyper-eosinophilic syndrome.
There are very few conditions where the eosinophil blood counts are low. One is usually encountered when corticosteroid is administered. In Alcohol intoxication and Cushing's disease low eosinophil count are seen.
Normal functions of Eosinophil.
Eosinophils are immunocytes that act by releasing preformed substances, contained in the cytoplasmic granules. The pathophysiology of diseases is different from disease to disease. The substances carried in the granules can be grouped into – Oxygen radicals, Enzymes, Leukotrienes, Cytokines, Prostaglandins and Growth factors. In previous blogs oxygen radicals, leukotrienes, prostaglandins and cytokines are discussed in detail and will not be repeated here.
Growth factors are TGF beta (tissue growth factor), VEGF beta (vascular endothelial growth factor), PDGE (platelet derived growth factor). In addition, the Eosinophils promote the development of post pubertal breasts, influence menstrual cycles and protect tissues from cancerous developments, prevent allograft rejection and help antigen presentation to T-Cells.
Hypereosinophilia
Hpereosinophilia is seen in these conditions – Allergy, Asthma, Roundworm infestation of the gut, and Cutaneous larval migration like Filaria, Trichinosis, Cysticercosis. Eczema and Atrophic dermatitis, Chung-Strauss syndrome, Autoimmune diseases, Crohn's disease, Addison disease, Cancers of breasts, ovaries, and prostate. Leukemia and among the group of leukemias - Acute myelogenous leukemia (AML) and Eosinophilic leukemia are particularly striking. It is also seen in certain Fungal infections. Many prescribed medications produce allergic dermatitis and Penicillin leads the group; Penicillin may also produce Interstitial nephritis which is characterized by the presence of eosinophils in the urine.
Hypereosinophilic syndrome
When peripheral blood eosinophil count is persistently over 1,500 mcL for 6 months or longer and evidence of organ damage and allergy, parasitic infection and chromosomal abnormality are eliminated the condition is called Hyper-eosinophilic syndrome (HES).
When the cause of high eosinophilia is known the term Secondary Hypereosinophilic Syndrome is applied and many of the old HES are now classified under Secondary HES.
Chromosomal abnormality in hyereosinophilia.
The translocation of the gene between F1P1L1 and PDGFRA of the long arm of chromosome 4, at location 12 (4q12) produces a hybrid gene (F/P) which produces excess IL-5 causing rapid and excessive eosinophil production. Many other less prevalent Myeloid dysfunction due to chromosomal abnormalities are known, some examples are Chronic Eosinophilic Leukemia, Lymphatic HES, and Myeloproliferative HES.
Organs damaged by HES.
Esophagus, Stomach and intestine, Skin, Lungs and Heart. Multiple organs involved are the usual but only one organ or one system may be involved.
Clinical manifestation of HES.
Presentation and clinical features vary due to different organ /system involvement. Incidence in the USA is 0.3 to 6.0 per 100,000 population, including secondary EHS. General- Males are more affected by HES and ages between 20 to 50 are mostly affected. Systemic symptoms are fever, loss of weight, weakness. lethargy, pain in joints and muscles, and night sweat. Skin manifestations are itchy macular and nodular eruptions, angioedema and eczema. GI symptoms are heart burns, abdominal pain and diarrhea. Heart problems may mimic MI, endomyocardial necrosis, peripheral emboli and cardiomyopathy. Lung lesions resemble an attack of asthma, pulmonary infiltration and interstitial pneumonia and fibrosis. Unproductive cough. Hematological manifestations are many, chief among them are anemia, enlarged spleen and liver, and fibrosis of bone marrow. High serum B12 level. CNS manifestations are peripheral neuropathy, Transient ischemic attacks, strokes, and encephalopathy.
Diagnosis requires a complete blood count, serum B12 level, bone marrow biopsy and chromosome study.
Treatment of HES.
Intravenous corticosteroid is used to bring down Eosinophil count rapidly, and Hydroxyurea is also used. Imatinib, a Tyrosine kinase inhibitor, is effective. Various other small molecules are available to suppress IL -5 production.
The prognosis is unfavorable without treatment. At present, with prompt treatment, the longevity on average is 80% in 5 years.
*************************************
No comments:
Post a Comment