Addison's anemia. Addison-Birmer disease

Otherwise, Addison-Birmer anemia, relatively rare disease, usually occurs in adults aged 45-60 years.

Interestingly, it is more common in people with the 2nd blood group and Blue eyes. It belongs to the group of megaloblastic anemias.

Causes of Vitamin B12 Deficiency

The cause of this disease is antibodies directed against the Castle factor (IF - intrisic factor), which, by binding to vitamin B12 in the stomach, ensures its transportation through the intestinal wall into the blood; and antibodies directed against the lining cells of the stomach, which produce acid. As a rule, vitamin B12 deficiency is accompanied by the diagnosis of inflammation of the gastric mucosa.

Other reasons leading to vitamin B12 deficiency this is:

improper diet (vegetarianism);
alcoholism;
congenital deficiency of the Castle factor;
condition after resection of the stomach - condition after resection small intestine;

Symptoms of Addison-Birmer disease

There are symptoms inherent in any other anemia, that is:

weakness and fatigue;
pain and dizziness;
fast heart rate (with a severe form of the disease);
pallor of the skin and mucous membranes.

There may also be diseases associated with the gastrointestinal tract:

signs of inflammation of the tongue (dark red or very pale tongue, burning);
inflammation of the oral cavity: redness, soreness, swelling;
loss of sense of taste;
constipation or diarrhea, nausea.

Neurological symptoms also develop:

feeling of numbness of hands and feet;
feeling of "tingling in the limbs";
sensation of current passing through the spine when the head is tilted forward;
unsteady gait;
memory loss and mental changes such as depression, hallucinations.

The more time has passed since the appearance neurological symptoms before the start of treatment, the less likely it is to recover. Changes that last longer than six months tend to last a lifetime.

Diagnosis of pernicious anemia

Noticing that the patient has symptoms of anemia, the doctor should order a blood test. If a decrease in the level of hemoglobin and red blood cells is detected, other blood parameters are also evaluated.

When megaloblastic anemia and pernicious anemia, observed increased size erythrocytes (MCV → 110). Then you must find out the reason for the incorrect metabolism of vitamins. In particular, assess the level of cobalamin in the blood: less than 130 pg/ml indicates its deficiency.

The content of methylmalonic acid in the blood and urine is also examined. It is formed in an increased amount in case of a lack of vitamin B12, so it increased content confirms malabsorption of the vitamin. When the level of cobalamin decreases, a study in the direction of antibodies attacking the Castle factor is recommended. When the result is negative, the Schilling test must be performed.

A favorable response of the body to treatment also indicates a deficiency of this vitamin. An increase in the number of young red cells in the blood after 5-7 days indicates their recovery. Pernicious anemia is effectively reversible with the addition of vitamin B12. Usually prescribed 1000 mcg per day for 2 weeks. After anemia symptoms change, the regimen of drug administration is changed and the drug is prescribed until the end of life.

Until the time of the discovery of vitamin B12, the disease was fatal and therefore was called malignant, today this name already has only historical value.

Symptoms of anemia (Addison-Birmer's disease)

Clinic

Addison-Birmer anemia most often affects women aged 50-60 years. The disease begins slowly and gradually. Patients complain of weakness, fatigue, dizziness, headache, palpitations and shortness of breath on movement. In some patients in clinical picture dyspeptic symptoms dominate (belching, nausea, burning at the tip of the tongue, diarrhea), less often nervous system(paresthesia, cold extremities, unsteady gait).

Objectively, pale skin (with a lemon tint), slight yellowness of the sclera, puffiness of the face, sometimes swelling of the legs and feet, and almost naturally - pain in the sternum when tapped.

The nutrition of patients was preserved due to a decrease in fat metabolism. The temperature, usually subfebrile, rises to 38-39°C during a relapse.

Characterized by changes in the digestive system. The edges and tip of the tongue are usually bright red with cracks and aphthous changes (glossitis). Later, the papillae of the tongue atrophy, in connection with which it becomes smooth, "varnished". Due to atrophy of the gastric mucosa, achilia develops and, in connection with it, dyspeptic symptoms (less often diarrhea). In half of the patients there is an increase in the liver, and in the fifth part - an increase in the spleen.

Changes in the cardiovascular system are manifested by tachycardia, hypotension, heart enlargement, deafness of tones, systolic murmur above the top and pulmonary artery, "the noise of the top" over the jugular veins, and in severe cases - circulatory failure. As a result dystrophic changes in the myocardium on the ECG, a low voltage of the teeth and an elongation of the ventricular complex are determined; T waves in all leads decrease or become negative.

Changes in the nervous system occur in approximately 50% of cases and are characterized by damage to the posterior and lateral columns. spinal cord(funicular myelosis), manifested by paresthesia, decreased tendon reflexes, impaired deep and pain sensitivity, and in severe cases - paraplegia and dysfunction of the pelvic organs.

On the part of the blood - a high color index (up to 1.2-1.3). This is due to the fact that the number of erythrocytes decreases to a greater extent than the hemoglobin content. At qualitative analysis a blood smear reveals pronounced macroanisocytosis with the presence of megalocytes and even single megaloblasts, as well as a sharp poikilocytosis. Often there are erythrocytes with the remains of nuclei - in the form of Cabot rings and Jolly bodies. On the part of white blood - leukopenia with hypersegmentation of neutrophil nuclei (up to 6-8 segments instead of 3). Permanent feature Birmer's anemia is also thrombocytopenia. The amount of bilirubin in the blood is usually increased due to increased hemolysis of megaloblasts and megalocytes, the osmotic resistance of which is reduced.

There are several types of pathologies associated with a lack of trace elements in the body. One of them is Addison Birmer's anemia. This is a malignant course of the disease, expressed in anemia in a deficiency of vitamin B12 and folic acid. The disease, which occurs in 30-50 cases per 10,000 of the population, is more prone to this ailment of women, and, at the age of over 50, the risk of developing the disease increases (possibly due to menopause).

Classification

For the first time, Addison Birmer's anemia develops with vitamin B12 deficiency, it was described in 1855 by Addison, later confirmed by Birmer, who studied the disease and gave a detailed clinical description. Subsequently, this condition was named after the names of its researchers. For a long time was considered an incurable disease, proceeding severely and uncontrollably. Currently, the pathogenesis of the disease is quite clear, but the etiology to a greater extent remains only an assumption.

Addison-Birmer anemia is characterized by the presence of a specific triad of disorders in the body:

Severe course of gastritis by atrophic type. going on gradual decline functions glandular epithelium, the mucosa is infiltrated, replaced by unusual this body cells, production is sharply reduced or stops altogether.
Inability to digest vitamin B12 and folic acid. Both components are necessary for building cells, with their help DNA is synthesized and the cell nucleus is formed correctly. With a lack of both of them, first of all, hematopoiesis and nervous tissue suffer.
Development of megaloblastic hematopoiesis. This is the formation of a multitude that are not able to perform their functions normally. In this course, Addison-Birmer anemia is similar to malignant.

The reasons

The main factor leading to the development of the disease, the cause of Addison Birmer's anemia, is atrophy of the gastric mucosa, as a result, the secretion (production) of pepsinogen stops. And the role of pepsinogen in the body is such that it provides transport and absorption of cyanocobalamin. However, atrophic gastritis does not always lead to the development of megablast anemia. Probably, several factors must coincide for the development of the disease.

The absorption of B12 and folic acid may be impaired due to extensive inflammation of the gastric mucosa and ileal calving or damage to their malignant tumors.

pernicious anemia to a large extent, is autoimmune disease, so in the blood serum of patients in 70 -75% of cases, antibodies to inner cells stomach. When conducting experiments on rats, it turned out that such cells lead to atrophy of the gastric glandular tissue. Similar antibodies are also present in gastric secretions. The autoimmune response is highly likely to be considered hereditary factor, since a certain amount of antibodies against parietal cells of the stomach, as well as cells endocrine system found in healthy relatives.

Additional but no less an important factor is a hereditary tendency to diseases of the pancreas.

A lifestyle that leads to failures in immune system, for example, experimenting with hard, abrupt transition to vegetarianism, uncontrolled intake medical preparations, violation of dosages in taking medications. What is important, in the post-war famine years, the incidence of pernicious anemia did not increase, which means that quantitative and qualitative malnutrition can only be attributed to concomitant causes.

There are scattered facts on the description of cases of incidence of megaloblastic anemia. For example: in the northern regions, this pathology is more common; there are indications of an increase in morbidity in people whose work is associated with lead and the possibility of slow carbon monoxide poisoning; after surgery to remove the stomach, when there is a total elimination of the secretory function, anemia can develop after 5-7 years; there is evidence of the development of megablast anemia as a result of toxic poisoning with chronic alcoholism.

Symptoms

Symptoms of Addison-Birmer anemia looks like as follows, erythrocyte cells of abnormal sizes are formed, with an overgrown cytoplasm, and their nuclei contain small inclusions.

Due to a critical lack of vitamin B12, a defect occurs in the metabolism of folic acid, which is involved in DNA synthesis. As a result, cell division is also disrupted in the periphery. The same quantitative and qualitative deformations occur with platelets. The bone marrow changes color, acquires a rich scarlet color, it is dominated by megablast immature cells, which, by the type of development, resemble the malignant course of blood diseases.

Vitamin B12 is used by the body not only for hematopoiesis, but also to provide normal operation nervous system. With its deficiency, dystrophy is observed in nerve endings spinal column.

From the side digestive system atrophy of the mucous membrane of the palate, pharynx, esophagus, stomach and intestines is detected. Perhaps the formation of polyps, a slight increase in the liver. The clinical course of the disease of Addison-Birmer anemia manifests itself gradually: periodically occurs great weakness, attacks of dizziness intensify, there is noise in the ears.

The resulting symptoms of Addison Birmer's anemia can be divided into manifestations:

from the nervous system: the regulation of movements is disturbed, paresthesia appears; there are pains in the intercostal space; sometimes there is damage to the visual and auditory nerve; .
from the side digestive tract: glossitis characterized by "varnished tongue" syndrome and pain in language; nausea, heaviness in the epigastric region, the formation of aversion to food, worsening taste sensations; an increase in the liver, less often - the spleen, the appearance of icterus of the sclera, mucous membranes;
external manifestations: pale skin with a yellowish tint, formed characteristic syndrome anemia Addison-Birmer - the face of a wax doll; puffiness of the face, significant swelling; lethargy, drowsiness.
on the part of the heart: the appearance, pain, degenerative changes in the myocardium.

Diagnostics

Diagnosis of anemia consists of several stages.

Visual examination reveals: pale skin, icteric hue of the sclera, dark spots on the face, hands and body. A characteristic picture is given by inspection oral cavity, on the initial stage disease, the tongue is painful, covered with small cracks. In the midst of the disease, the tongue becomes scarlet and puffy, looks like varnished. When a slight increase in the liver is detected and its protrusion beyond the edge of the rib. The spleen enlarges in a small number of patients. Conducting neurological tests reveals a change in sensitivity in the limbs.

When diagnosing Addison-Birmer anemia, a blood test plays a key role. Thorough research in progress peripheral blood, where a significant increase in erythrocyte blood volume is detected, while the number of reticulocytes is sharply reduced. The presence of hyperchromic erythrocytes is detected. The main sign of megablast anemia can be considered the presence of hypersegmental neutrophils (having five or more segments in the nucleus). In a relatively healthy person, such cells occur within 2%, in those suffering from pernicious anemia, the number of hypersegmental neutrophils rises above 5%.

Equally important is research bone marrow with anemia. It reveals megaloblastic growth of cells - these are cells that have stopped in their development, preceding erythrocytes. They are abnormally enlarged, deformed, with noticeable difference in the level of development of the nucleus and cytoplasm. In general, unproductive erythropoiesis - feature megablast anemia. The vast majority of immature and deformed erythrocyte cells (megablasts) are destroyed even in the bone marrow without entering the bloodstream. With the progression of the disease, the number of reticulocytes continues to fall, while their deformation occurs.

Instrumental diagnostics includes: research gastric juice, where, as a rule, a decrease in acidity or its complete absence is found out. But there is significant amount mucus, similar in composition to intestinal. Held endoscopy, where extensive atrophy of the gastric mucosa, often called "pearl plaques", loss of secretory cells is clearly observed. Unfortunately, even during remission, pepsinogen synthesis is not restored.

often carried out histological examination tissues, since one of the causes that can cause Addison Birmer's anemia is malignant neoplasms.

These patients require further consultation. narrow specialists: neurologist, endocrinologist, cardiologist, immunologist.

A mandatory diagnostic method is the Schilling test. This method aims to differentiate folate deficiency anemia from B12 deficiency anemia in order to identify the underlying cause, and outline proper treatment. To do this, measure their concentration in blood serum. The norm of folic acid is 5-20ng / ml, the norm of B12 is 150-900ng / ml. Indicators below these limits indicate the presence of a deficiency of these components in the body. To conduct a test, the patient is injected with vitamin B12 intramuscularly, after a sufficient time, its concentration in the urine is determined, a small amount for B12-deficiency anemia, the maximum - for folic deficiency.

Folic acid deficiency in the body is more common in young age and does not have contributing factors atrophy of the secretory function of the stomach and the presence of neurological symptoms. It responds favorably to oral folic acid and responds better to treatment. When examining patients with B12 deficiency anemia, it is important to establish the underlying cause of the disease.

Treatment

Treatment of anemia Addison Birmer has its own characteristics. Choice medicinal product depends on the cause of the disease. Folic deficiency anemia occurs due to a violation of its absorption in the intestine. common cause This is chronic alcoholism, and it is especially dangerous during pregnancy.

The lack of folic acid is more favorable for the body in terms of treatment, since it does not affect the secretory function of the stomach, and oral administration therapeutic doses the drug gives a quick effect.

Folic acid is available as separate drug in the form of tablets or solution for injection, and as part of complex vitamins. Side effects when taking folic acid in the treatment of anemia are rare, but possible allergic reactions on the intramuscular injection drug.

In the case of vitamin B12 deficiency in the body, the use of tablet forms is not justified, since the presence of atrophic gastritis reduces similar treatment to zero. In the treatment of this type of anemia, intramuscular or subcutaneous injections cyanocobalamin. Intravenous administration drug is dangerous. Cyanocobalamin is a pinkish liquid, in 1 ml ampoules, sometimes its use can cause allergic rash. The drug is administered daily at a dose of up to 500 mg, for 6 weeks, additionally administered folic acid at doses up to 100mg.

With mild or medium degree severity of anemia, treatment may be delayed until after complete diagnosis and identifying the causes of shortages. With severe neurological disorders and significant changes in the blood picture, treatment is started immediately.

Often, external signs anemia of Addison-Birmer disappear in the first days of treatment. Pain in the tongue and mouth subsides, appetite appears, weakness disappears, vision and hearing are restored. After a few days, reticulocytosis is restored, the number of megablasts in the bone marrow is sharply reduced. Recovery of hematopoiesis usually occurs after 1-2 months. Heavy neurological disorders may retain their symptoms for several months, or may not completely disappear at all.

With severe atrophy of the gastric mucosa and with B12-deficiency anemia, preparations containing vitamin B12 have to be taken throughout life. The patient should be aware that the failure of maintenance therapy entails a relapse of megaloblastic anemia. As a rule, those who have been ill with Addison-Birmer anemia are registered in the dispensary and are under regular observation. Maintenance doses are administered in short courses as prescribed by a doctor and under constant monitoring of the blood picture.

Preparations for prevention

In order to prevent anemia, folic acid is prescribed only to certain groups of citizens. For example, pregnant women to prevent pathologies of the spinal cord in the fetus, nursing mothers, for proper development child. Elderly people with some forms of anemia, as well as patients who are in coma. In all other cases, the amount that comes with food in the normal diet is sufficient.

Vitamin B12 for prevention purposes is prescribed only with a possible deficiency, for example, with veganism or total removal of the stomach. Cyanocobalamin has a wide reputation as a general tonic, which is completely unproven, but it is often prescribed for general exhaustion, fatigue and increased fatigue as a tonic. Given the need for B vitamins in the regulation of the nervous system, it is possible to use cyanocobolamin to treat inflammation. trigeminal nerve and other neuropathies.

Treatment of Addison Birmer's anemia with any vitamin preparations must be strictly targeted. And only if there is a suspicion of a deficiency of several vitamin components, you can take multivitamin complexes.

- a violation of the red germ of hematopoiesis, due to a lack of cyanocobalamin (vitamin B12) in the body. With B12-deficiency anemia, circulatory-hypoxic (pallor, tachycardia, shortness of breath), gastroenterological (glossitis, stomatitis, hepatomegaly, gastroenterocolitis) and neurological syndromes(disturbance of sensitivity, polyneuritis, ataxia). Pernicious anemia is confirmed by results laboratory research(clinical and biochemical analysis blood, bone marrow punctate). Treatment for pernicious anemia includes balanced diet, intramuscular injection of cyanocobalamin.

ICD-10

D51.0 Vitamin B12 deficiency anemia due to intrinsic factor deficiency

General information

Pernicious anemia is a type of megaloblastic deficiency anemia that develops with insufficient endogenous intake or absorption of vitamin B12 in the body. "Pernicious" in Latin means "dangerous, disastrous"; in the domestic tradition, such anemia used to be called " malignant anemia". In modern hematology, pernicious anemia is also synonymous with B12-deficiency anemia, Addison-Birmer disease. The disease occurs more often in people older than 40-50 years, somewhat more often in women. The prevalence of pernicious anemia is 1%; however, about 10% of older people over the age of 70 suffer from vitamin B12 deficiency.

Causes of pernicious anemia

The daily human need for vitamin B12 is 1-5 micrograms. It is satisfied by the intake of vitamin with food (meat, fermented milk products). In the stomach, under the action of enzymes, vitamin B12 is separated from dietary protein, but for absorption and absorption into the blood, it must combine with a glycoprotein (Castle factor) or other binding factors. The absorption of cyanocobalamin into the bloodstream occurs in the middle and lower part ileum. The subsequent transport of vitamin B12 to tissues and hematopoietic cells is carried out by blood plasma proteins - transcobalamins 1, 2, 3.

The development of B12-deficiency anemia can be associated with two groups of factors: alimentary and endogenous. Nutritional causes are due to insufficient intake of vitamin B12 with food. This can occur with fasting, vegetarianism, and diets that exclude animal protein.

Under endogenous causes implies a violation of the absorption of cyanocobalamin due to a deficiency of the internal factor of Castle with its sufficient intake from the outside. Such a mechanism for the development of pernicious anemia occurs in atrophic gastritis, a condition after gastrectomy, the formation of antibodies to internal factor Castle or parietal cells of the stomach, congenital absence factor a.

Violation of the absorption of cyanocobalamin in the intestine can be observed with enteritis, chronic pancreatitis, celiac disease, Crohn's disease, diverticula small intestine, tumors of the jejunum (carcinoma, lymphoma). Increased consumption of cyanocobalamin may be associated with helminthiases, in particular, diphyllobothriasis. There are genetic forms of pernicious anemia.

Vitamin B12 absorption is impaired in patients undergoing small bowel resection with gastrointestinal anastomosis. Pernicious anemia may be associated with chronic alcoholism, the use of certain medicines(colchicine, neomycin, oral contraceptives and etc.). Since the liver contains a sufficient reserve of cyanocobalamin (2.0-5.0 mg), pernicious anemia develops, as a rule, only 4-6 years after the violation of the intake or absorption of vitamin B12.

In conditions of vitamin B12 deficiency, there is a deficiency of its coenzyme forms - methylcobalamin (participates in the normal course of erythropoiesis processes) and 5-deoxyadenosylcobalamin (participates in metabolic processes occurring in the central nervous system and peripheral nervous system). The lack of methylcobalamin disrupts the synthesis of essential amino acids and nucleic acids, which leads to a disorder in the formation and maturation of red blood cells (megaloblastic type of hematopoiesis). They take the form of megaloblasts and megalocytes, which do not perform an oxygen transport function and are rapidly destroyed. In this regard, the number of erythrocytes in the peripheral blood is significantly reduced, which leads to the development of anemic syndrome.

On the other hand, with a deficiency of the coenzyme 5-deoxyadenosylcobalamin, the metabolism fatty acids, resulting in the accumulation of toxic methylmalonic and propionic acid that have a direct damaging effect on the neurons of the brain and spinal cord. In addition, myelin synthesis is disrupted, which is accompanied by degeneration of the myelin layer. nerve fibers- this is due to damage to the nervous system in pernicious anemia.

Symptoms of pernicious anemia

The severity of pernicious anemia is determined by the severity of circulatory-hypoxic (anemic), gastroenterological, neurological and hematological syndromes. Signs of an anemic syndrome are nonspecific and are a reflection of a violation of the oxygen transport function of erythrocytes. They are represented by weakness, decreased endurance, tachycardia and palpitations, dizziness and shortness of breath when moving, low-grade fever. On auscultation of the heart, a whirlpool or systolic (anemic) murmur may be heard. Externally, there is pallor of the skin with a subicteric shade, puffiness of the face. A long "experience" of pernicious anemia can lead to the development of myocardial dystrophy and heart failure.

Gastroenterological manifestations of B12-deficiency anemia are decreased appetite, stool instability, hepatomegaly ( fatty degeneration liver). classic symptom, detected in pernicious anemia - "varnished" crimson tongue. The phenomena of angular stomatitis and glossitis, burning and pain in language. Gastroscopy revealed atrophic changes gastric mucosa, which are confirmed by endoscopic biopsy. Gastric secretion is sharply reduced.

Neurological manifestations of pernicious anemia are caused by damage to neurons and pathways. Patients indicate numbness and stiffness of the limbs, muscle weakness, gait disturbance. Possible incontinence of urine and feces, the occurrence of persistent paraparesis lower extremities. An examination by a neurologist reveals a violation of sensitivity (pain, tactile, vibration), increased tendon reflexes, symptoms of Romberg and Babinsky, signs of peripheral polyneuropathy and funicular myelosis. B12 deficiency anemia can develop mental disorders- insomnia, depression, psychosis, hallucinations, dementia.

Diagnosis of pernicious anemia

In addition to a hematologist, a gastroenterologist and a neurologist should be involved in the diagnosis of pernicious anemia. Vitamin B12 deficiency (less than 100 pg / ml at a rate of 160-950 pg / ml) is established during biochemical research blood; it is possible to detect antibodies to the parietal cells of the stomach and to the internal factor of the Castle. For general analysis blood typical pancytopenia (leukopenia, anemia, thrombocytopenia). Microscopy of a peripheral blood smear reveals megalocytes, Jolly and Cabot bodies. Examination of feces (coprogram, analysis for eggs of worms) can reveal steatorrhea, fragments or eggs of a wide tapeworm in diphyllobothriasis.

The Schilling test allows you to determine the malabsorption of cyanocobalamin (by urinary excretion of labeled radioactive isotope vitamin B12 taken orally). Bone marrow puncture and myelogram results reflect an increase in the number of megaloblasts characteristic of pernicious anemia.

To determine the causes of impaired absorption of vitamin B12 in the gastrointestinal tract, EGD, radiography of the stomach,

Secondly, patients have circulating autoantibodies: in 90% - to the parietal cells of the stomach, in 60% - to the intrinsic factor of Castle. Antibodies to parietal cells are also detected in every second patient with atrophic gastritis without impaired absorption of vitamin B12 and in 10-15% of randomly selected patients, but they, as a rule, do not have antibodies to the internal factor of the Castle.

Thirdly, relatives of people with Addison-Birmer's disease are more likely to suffer from this disease, and even in those who do not have anemia, antibodies to the intrinsic factor of Castle can be detected.

The clinical picture consists mainly of signs of vitamin B12 deficiency (see "Vitamin B12 deficiency: an overview"). The disease begins gradually and progresses slowly. Laboratory examination reveals hypergastrinemia and absolute achlorhydria (hydrochloric acid is not produced even in response to the administration of pentagastrin), as well as changes in the blood picture and other laboratory parameters (see "Megaloblastic anemia: diagnosis").

Replacement therapy completely and permanently eliminates in these patients the disorders caused by vitamin B12 deficiency, except in those cases when irreversible changes in nervous tissue occurred before treatment. However, patients are extremely predisposed to adenomatous polyps of the stomach and are about twice as likely to develop gastric cancer. They are shown observation, including regular guaiac testing, and, if necessary, additional studies.