Addison-Birmera's disease

Description:

Pernicious anemia (Addison-Birmera's disease) — the disease which is characterized by a megaloblastny hemopoiesis and (or) changes of a nervous system owing to deficit of B12 vitamin which arises at heavy atrophic gastritis. Frequency of pernicious anemia makes 110 — 180 cases on 100 000 population. Among persons 60 years frequency are more senior reaches 1%. At family predisposition to pernicious anemia the contingent of patients was younger. The ratio of sick women and men constantly makes 10:7.

Symptoms of the Disease of Addison-Birmera:

Patients with pernicious anemia complain of fatigue, drowsiness, vitality loss. Twenty five percent of patients complain of mouth pains or in language, and one third — of symmetric paresthesias in the lower and (or) upper extremities. Some decrease in body weight and loss of appetite are observed. Much less often disturbances of gait, an urination, impotence, visual disturbances meet and it is absolutely rare — hallucinations and even mental disturbances.

At inspection usually find the varnished language; in case of more expressed anemia — pallor of skin and some yellowness of scleras. Neurologic inspection allows to reveal a pallesthesia, passive mobility, and sometimes and other signs of defeat of side and back columns of a spinal cord.

Etiologies of Addison-Birmera:

Three factors are involved in development of pernicious anemia: a) family predisposition, b) heavy atrophic gastritis, c) communication with autoimmune processes.

There passed more than 130 years since Fenwick (1870) found a mucosal atrophy of a stomach and the termination of development of a pepsinogen in patients of pernicious anemia. The achlorhydria and practical lack of an internal factor in a gastric juice are characteristic of all patients. Both substances are produced by covering cells of a stomach. The atrophy of mucous takes proximal two thirds of a stomach. The most part of the cosecreting cells or all of them perish and are replaced with muciparous cells, sometimes intestinal type. Lymphocytic and plazmotsitarny infiltration is observed. Such picture, however, is characteristic not only of pernicious anemia. It is found also at simple atrophic gastritis in patients without hematologic deviations, and at them even in 20 years of observation pernicious anemia does not develop.

The third etiological factor is presented by an immune component. Two types of autoantibodies are found in patients of pernicious anemia: to covering cells and to an internal factor.

By immunofluorescence method in serum of 80 — 90% of patients of pernicious anemia reveal the antibodies reacting with covering cells of a stomach. The same antibodies are present at serum of 5 — 10% of healthy faces. At women of old age the frequency of detection of antibodies to covering cells of a stomach reaches 16%. At microscopic examination of bioptat mucous a stomach almost gastritis is found in all persons having in antibody serum to covering cells of a stomach. Introduction to rats of antibodies to covering cells of a stomach leads to development of moderate atrophic changes, considerable decrease in secretion of acid and an internal factor. These antibodies, obviously, play an important role in development of a mucosal atrophy of a stomach.
Antibodies to an internal factor are present at serum of 57% of patients of pernicious anemia and seldom are found in the persons who do not have this disease. At peroral introduction of an antibody to an internal factor suppress absorption of B12 vitamin owing to connection them with an internal factor that interferes with linkng of the last with B12 vitamin.

Such antibodies are present not only at serum, but also in a gastric juice and are developed by plasmocytes in mucous a stomach. So, the gastric juice can contain class IgA antibodies, and in serum — the class IgG. At some patients of an antibody are present only at a gastric juice. On the basis of the antibodies given about detection both in serum, and in a gastric juice it is possible to draw a conclusion that such antibodies to an internal factor come to light approximately at 76% of patients.

Other form of an immune response on an internal factor is the cellular immunity revealed in tests of an ingibition of migration of leukocytes or a blasttransformation of lymphocytes. Cellular immunity is found in 86% of patients. If to combine results of all tests, i.e. data on existence of humoral antibodys in serum, in a gastric secret, cell-bound immune complexes in a gastric secret and cellular immunity to an internal factor, then it will turn out that the immune component is present at 24 of 25 patients of pernicious anemia.

On modern representations, lymphocytes contain all necessary information for development of any antibodies, but products of antibodies are controlled by suppressor T lymphocytes. For not clear reasons at a number of diseases V-lymphocytes escape from under control of suppressor cells and develop "autoantibodies" against covering cells, an internal factor and is quite frequent against cells of a thyroid gland, epithelial bodies, adrenal glands and islets of Langerhans. Tendency to development of autoantibodies has family character, in any case these antibodies with high frequency are found in healthy relatives, and at some relatives develops the corresponding diseases. It is not clear what is primary in development of atrophic gastritis. Antibodies to covering cells prevent normal regeneration of a mucous membrane. It is not excluded that antibodies start atrophic process. Steroids, destroying lymphocytes, promote involution of process and regeneration of an atrophied mucous membrane. The atrophy significantly reduces the volume of gastric secretion and development of an internal factor.

Antibodies to an internal factor neutralize its residual quantities owing to what absorption of B12 vitamin decreases to inadequate level. There is a negative balance of B12 vitamin and slowly its deficit develops. The B12 vitamin absorption termination (after a total gastrectomy) results in deficit in 5 years, and at smaller degree of negative balance the bigger span before development of manifest deficit is required respectively.

Treatment of the Disease of Addison-Birmera:

For recovery of reserves of B12 vitamin in the beginning usually do about 6 injections on 1 mg of Oxycobalaminum. Oxycobalaminum is late in an organism much better, than cyanocobalamine. So, from 1 mg of the entered Oxycobalaminum in an organism there are about 70 — 80%. At introduction of a comparable dose of cyanocobalamine less than 30% are late. There are no data that the group of cyan of a molecule of cyanocobalamine can have harmful effect.

The maintenance therapy has to be directed to daily consumption about 5 mkg of B12 vitamin that 250 mkg of Oxycobalaminum are reached by means of introduction once a month. The drug needs to be administered during all life of the patient. 3 — 6 months later at a small number of patients deficit of iron develops what falling the MCV lower than 80 фл testifies to. In such cases the short course of peroral iron preparations is shown.

Normalization of indicators of blood depends on initial weight of anemia. At patients with heavy anemia time of life of erythrocytes is considerably reduced, and recovery of normal value MCV happens especially quickly (25 — 35 days). At slight anemia time of life of erythrocytes is normal, and recovery of normal value MCV takes up to 80 days.

Treatment leads to elimination of a neuropathy, at all patients the incontience of urine and other symptoms disappears. Paresthesias disappear in 4 — 6 months. The sight broken owing to an atrophy of an optic nerve is not recovered, however if the vision disorder is caused by hemorrhages to the area of a macula lutea, then recovery happens quickly.

It must be kept in mind that the myxedema is found in many patients from pernicious anemia in several years. From 5217 patients of pernicious anemia 1,8% had a diffusion toxic craw and at 2,4% — a myxedema. In 9% of patients with primary hypothyroidism it is found pernicious anemia.
According to Zamcheck and соавт., at 5,8% of patients finally the carcinoma of the stomach developed. In two Scandinavian researches it is shown that the frequency of pernicious anemia among patients with cancer of a stomach, revealed at autopsy, made 2,1-2,2%.