Weakens of Biermer

The weakens of Biermer (also called weakens pernicious ) is due to a deprives of Vitamine B12 (Cyanocobalamine). This deficiency in Vitamine B12 is generally the consequence of a deficit of secretion by the intestinal mucous membrane of extrinsic Facteur of Castle.

The Anémie is of slow installation, and can thus be rather important (6 grams of Hémoglobine per decilitre of blood) and yet pass unperceived. The clinical signs of anemia (Asthenia, Paleness, Polypnée, Tachycardia) will be definitely more moderate than for an anemia of brutal installation.

Etiology of the pernicious anemia of Biermer

This affection is frequent at the human type Caucasien , rare on the contrary at the other types. It assigns mainly people of more than 40 years. Youthful pernicious anemia exists but is very rare and appears in the teenager or the young adult. It is very similar to the disease of Biermer and which had, like it, with an absence of secretion of intrinsic Facteur. Here however, the gastric Muqueuse is not atrophied and it secret Hydrochloric acid , at least after stimulation with the Histamine. The origin of this disease is not known. The treatment, containing B12 vitamin, is identical to that of the anemia of Biermer.

Pernicious anemia (A.P.) watch a very clear Hereditary predisposition and family. One knows cases of A.P. among twins Univitellin S. In certain families one will find subjects reached of A.P., others of essential hypochromic anemia, others still apparently unscathed but presenting a gastric Achylie with or without deficit of resorption of B12 vitamin. One also insisted on a type Somatique which, without being very characteristic, is found however with a great frequency at the feeble pernicious ones: broad breadth, large and broad figure, drawn aside eyes, tendency to obesity.

It is necessary to also note the tendency of a.P. to association with other morbid entities : the Diabetes, the Hypothyroïdie and especially the gastric cancer .

The frequency of the malignant and benign tumors (Polyp S supposed précancéreux) of the stomach in a.P. is estimated at 13 %; this high rate justifies the systematic exploration of the stomach among Biermériens patients.

Pathogenesis

Pernicious anemia (A.P.) is due to a defect of intestinal resorption of the B12 vitamin, in consequence of a lack of intrinsic Facteur

It is an auto-immune disease with antibodies directed against the intrinsic factor: anemia is due to a defect of intestinal resorption of the vitamin B12 , in consequence of a lack of intrinsic factor. The lack of intrinsic secretion of factor is itself the consequence of an atrophy of the gastric mucous membrane , whose Achlorhydrie histamino-refractory is only another demonstration, just as the tendency to canceration. The first cause reside-T-it there? One currently thinks of being able to go up higher, and to be able to accuse a autoimmunization against the gastric mucous membrane . Often, indeed, the serum of feeble pernicious contains auto- Anticorps reacting with extracts of gastric mucous membrane, and sometimes with the intrinsic factor itself . Besides these patients present often a Hypergammaglobulinémie. Some think that the Diabète and the Myxoedème which so readily a.P. joins, could be parallel demonstrations of anti-pancreatic and anti-thyroid autoimmunity .

Clinical signs of the pernicious anemia of Biermer

The beginning is extremely insidious. At the stage of state one can raise three orders of clinical signs: 1) anemia 2) the nervous attack 3) the gastric achylie

1) the feeble syndrome : pernicious anemia, by its progressive beginning as much as by its character hyperchrome, is surprisingly well tolerated. The subject can sometimes carry on an community activity moderated with a number of red globules of about 2,5 X 10E6/mm ³. Certain patients present themselves with figures still much low (a million). The general state is remarkably well preserved. The temperature is subfébrile (37,5°C) and can become definitely feverish during the crises of deglobulisation. The dye is pale, but with a subicteric nuance. The Rate is generally palpable (hyperbilirubinemy), without being very large.

2) the nervous syndrome : certain neurons need B12 vitamin. The nervous syndrome is frequently lacking at the initial stage, but is not long in appearing with long. The nervous signs most important are those which derive from the atrophy of the posterior and side cords of the Spinal-cord. One will note a combination, in variable proportions from one case to another, following signs: a) of the driving disorders in 25 % of the cases b) of the sensory disorders (Paraesthesia S of the fingers and the toes) in 80 with 90 % of the cases (from where more frequent but much less serious) c) in the most serious cases only, of the disorders sphinctériens (urinary incontinence) and psychic (personality disorders, hallucinations). With insufficient amount, the B12 vitamin easily makes disappear anemia without acting on the nervous syndrome, whose treatment requires more important amounts.

3) the digestive symdrome : a) On the level of the mouth, one observes the Glossite de Hunter in 50 % of the cases. It is an early and important sign pernicious anemia. The language is smooth and brilliant in consequence of the atrophy of the lingual Papille S. It often carries small very painful erosions. The patient complains about feelings of burn when the food arrives in contact with the language. b) the stomach is the seat of an important lesion, causes disease: the Atrophy of the mucous membrane, person in charge of the achilie and the hydrochloric anacidity histamino-refractory. The test with the Histamine is always negative and, so a great importance for the diagnosis has. The Biopsie of the gastric mucous membrane confirms the diagnosis of Gastrite atrophic. The radiological Examen will be practiced systematically, less to objectify the atrophy of the mucous membrane, which it shows badly, which for the tracking of the Polype S and the gastric Cancer whose frequency is very high in this affection.

Analyzes of laboratory in pernicious anemia

1) Numération Formulates Blood :

a) Constants érythrocytaires:

reduction in the number of red globules which can fall to very low figures (2,5x 10 exhibitor 6/mm ³).
the rate of Hémoglobine drops relatively less, anemia being macrocytaire; the globular rate of hemoglobin generally lies between 33 and 38 Picogramme S.
macrocytose (VGM > 100). A VGM (average globular volume) high defines the macrocytose.
the average corpuscular concentration in hemoglobin (CCMH) is normal (either about 34 %), except if there is an associated martial deficiency (in which case there is a fall of the CCMH, = hypochromy). The hyperchromy does not exist: if a red globule macrocytaire contains more hemoglobin than a red globule normocytaire, that is due only to the volume effect, and not to the concentration effect.

b) Numeration of the elements, examination of the blood smear:

one will note especially the Macrocytose. The largest elements called Mégalocyte S have a globular diameter exceeding 10 Micron S, and draw easily the attention
it exists strong a Anisocytose and the Poïkilocytose is clear
blood generally contains immature forms: nucleate cells (érythroblaste S). These last are also of great dimension (Mégaloblaste S).
the discovery of a mégaloblastose is practically Pathognomonique of a.P., but these cells are not found that in the serious cases
the rate of Réticulocyte S is moderately increased
the osmotic Résistance of the G.R. is normal and thus does not explain the abnormal brevity of their survival

The B12 vitamin is necessary for the development of the hematologic cells with renouvellemnt fast. In addition to anemia one can thus also find a leucopenia and a thrombopénie.

the Leucopenia (300 with: 5000/mm ³) is due to neutropenia (<1500/mm ³). The white globules (G.B.) granulocytaires present a cellular gigantism and have a hypersegmenté Noyau (higher than 5 lobes for the neutrophiles). One can observe some young forms.

2) Examen of the osseous Moelle

marrow is rich in cells, with an important Hyperplasie of the red line
all the anomalies found on the level of blood come from marrow.
This richness appears somewhat paradoxical, being given poverty in blood cells. But a good part of the medullary érythropoièse is ineffective, much of G.R. being destroyed before to have left marrow. The ferrokinetic studies showed that this intramedullary shunt can reach 40 % of the production of Hb.

3) metabolic Data

the serum rate of iron is high, as in haemolytic anemias. The rate of saturation of the Transferrine is thus increased.
the globular Protoporphyrine is normal but the urinary excretion of Coproporphyrine is slightly increased.
There exist different Stigmate S from a haemolytic state, at the same time because of the intramedullary shunt that because of the shortening of the average globular life: Hyperbilirubinémie (Bilirubine non-conjugée, Urobilinurie, fecal increase in Stercobiline, disappearance of the Haptoglobine of the serum.
Not more deficiency in Folate S than for the remainder of the population.

4) specialized Tests , they are old diagnostic methods, today more rarely used:

a) gastric Casing with test with the Histamine , intended to highlight the anacidity and its character histamino-refractory.

b) Test of Schilling = test of intestinal resorption of the B12 vitamin marked with the radioactive Cobalt . At the feeble pernicious one, which does not reabsorb the B12 vitamin given per bone, the urinary excretion varies between 0 and 7 %; at the normal subject, one finds 11 with 16 % of the radioactivity of the tracer amount in the urines of the first 24 h. The test of Schilling is standardized during the intrinsic administration of factor, but not, obviously, during the treatment the B12 vitamin.

Evolution and forecast

Left without treatment, the pernicious anemia of Biermer evolves/moves by crises of deglobulisation. Before the discovery of the specific treatment, death occurred in general between 3 and 5 years.

Currently , thanks to the substitute treatment the vitamin B12, pernicious anemia became a benign affection . There remain however 2 dangers to supervise : the risk of canceration of the stomach (more or less 10 %) and is likely it to see hatching of the turbid highly-strung persons among patients receiving an insufficient treatment.

Diagnosis of the pernicious anemia of Biermer

When the table of anemia macrocytaire, glossite and nervous disorders is complete, the diagnosis of pernicious anemia is already highly probable. The diagnostic one of confirmation will be done by the proportioning of the B12 vitamin, and especially by the fast increase in the réticulocytes after treatment the B12 vitamin (test diagnoses), it is what one calls the " crisis réticulocytaire".

For the rough cases, one will attach also importance to the following points:

presence of Mégaloblaste S in peripheral blood (seldom abundant) and especially in osseous marrow.
hypersegmentation and gigantism of the G.B. (white globules) Granulocytaire S
achylie achlorhydric histammino-refractory.

Treatment of pernicious anemia

1) Substitute treatment specific to the B12 vitamin

Essence and with him only sufficient, the substitute treatment the B12 vitamin must comprise a cure of attack to important amounts, aiming stopping progress of the nervous attack and at repairing anemia then a treatment of maintenance intended to last all the remaining life of the patient. the B12 vitamin will be managed by intramuscular injection

2) Additional treatments of the feeble Syndrome

the Fer is contra-indicated in theory, at least at the beginning. There will be recourse there that whenever it is noted that anemia incompletely corrected and took a character Hypochrome making suspect a state ferriprive: in this case one will make a martial assessment (proportioning of the rate of iron serum or ferritin). If there is martial deficiency one will seek a cause of hemorrhage (gastric cancer…)
the Folic acid against is clearly indicated because it worsens the deficit in B12 vitamin.
Of other hematopoietic vitamins and factors are generally useless.

3) Treatment of the nervous syndrome

Led well, the treatment the B12 vitamin definitively stops the progression of the attack of SNC (central nervous system).

4) Treatment of the digestive syndrome

The Glossite and the Oesophagite cure quickly thanks to the B12 vitamin. The atrophy of the gastric mucous membrane is final. It is recommended to make an annual control fibroscopic of the stomach to detect in time a gastric cancer. The radiography of the stomach is seldom used nowadays.

Other anemias macrocytaires

1) youthful pernicious anemia

It is about a very rare syndrome , appearing in the teenager or the young adult, very similar to the anemia of Biermer, and whom had, like it, with a abscence of secretion of intrinsic Facteur. Here however, the gastric mucous membrane is not atrophied and it secret hydrochloric acid (HCl), at least after stimulation with the Histamine. the origin of this disease is not known . The treatment, containing Vitamin B12, is identical to that of the anemia of Biermer.

2) anemia macrocytaire of the digestive affections

It is frequent to observe an anemia moderated during a whole series of affections characterized by an insufficiency of the digestive functions, and in particular:

in the syndromes of Malabsorption intestinal (Sprue tropical, disease Céliaque of the child, Stéatorrhée idiopathic of the adult
after wide intestinal résections, in the intestinal Sténose S, the Dent S gastro-colics, etc…
in the after-effects of Gastrectomie
in the gastric Cancer

3) anemia macrocytaire of the carriers of Bothriocéphale (Diphyllobothrium) (Fish tapeworm disease)

Unknown factor in Belgium and little attends in France, this affection exists in Finland, in Switzerland, in the area of the American big lakes and generally where the population makes a fresh water fish consumption insufficiently cooked during the culinary preparation. The parasite consumes great quantities of Vitamine B12, thus depriving its host of this crucial factor. The anemia which results from it has all the characters of the anemia of safe Biermer, naturally, the Achylie histamino-refractory. Anemia cures by the expulsion of the worm, which constitutes the essence of the treatment, with the administration of high amounts of B12 vitamin.

4) anemia macrocytaire of the pregnancy

This form of anemia of the pregnancy was especially announced among the poor classes of the English population, and this at one time of economic depression. It is virtually unknown in Belgium. It cures spontaneously after the childbirth and would rest above all on a deficiency in Folic acid.

5) anemia macrocytaire of the chronic affections of the Liver

A light or moderate anemia belongs to the syndrome of the hepatic Cirrhose. It can be Microcytaire - Hypochrome in the event of repeating hemorrhages but more often it is slightly Macrocytaire and Hyperchrome. The pathogenesis of this anemia of the chronic affections of the liver is complex. Globular survival is somewhat shortened and part of the érythropoièse is inefficiente (intramedullary shunt). These anomalies evoke, in smaller, that of pernicious anemia. It is thought that they are multiple deficiencies of principles erythropoietic, due to an insufficient storage of these factors in the liver. The B12 vitamin, the folic acid and the total extracts of liver generally give an answer Réticulocytaire, but are in general unable to bring the complete repair of anemia. Other still obscure factors (like microbial Endotoxine S not destroyed by the liver?) must be taken into account.

6) anemia macrocytaire due to the Antimétabolite S

The Améthoptérine (Méthotrexate), which is an antagonist of the Folic acid , and the 6-mercaptopurine, which inhibits the synthesis of the Thymidine, are drugs usually used in the treatment of leukemias and other malignant affections of blood. They can with long producing an anemia of the macrocytaire type and hyperchrome.

7) tropical anemia macrocytaire

Described in Asia and Africa, this anemia is probably due to multiple deficiencies, interesting mainly the Folic acid and incidentally the Fer and the Vitamine B12.

8) rare anemias macrocytaires of not elucidated origin

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