Pernicious anemia

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Classification according to ICD-10
D51.0 Vitamin B 12 deficiency anemia due to lack of intrinsic factor
ICD-10 online (WHO version 2019)

The pernicious anemia (Latin pernicious anemia , short pernicious anemia , by pernicious = harmful, corrupting), and pernicious anemia or beer Mersche anemia (named after Anton anemia ) and Addison's anemia , or Addison's anemia (named after Thomas Addison ), is a form of Anemia ( anemia ) due to a lack of vitamin B 12 . In a narrower sense, the term pernicious anemia (M. Biermer) is only used for those forms in which the formation of the intrinsic factor is disturbed. Vitamin B 12 plays an important role in blood formation and in the breakdown of so-called odd - numbered fatty acids ; it is also important for the synthesis of DNA .

Vitamin B 12 can only be produced by microorganisms. These can be found in the intestinal flora of animals and humans. The occurrence in animal foods such as liver is due to the storage of the ingested vitamin B 12 in the animal organism. The daily requirement is 2–6 µg. The vitamin is absorbed from food in the intestine with the help of a special protein molecule ( intrinsic factor ) released in the stomach , which binds the vitamin and thus protects it from being destroyed. In the duodenum, passive uptake by diffusion takes place in parallel. This is proportional to the amount of vitamin B 12 present , with around 1–5% of the free cobalamin being absorbed through passive diffusion through the intestinal mucosa.

A deficiency in B 12 can lead to anemia and / or various neurological damage. If left untreated, it can lead to death.

Causes of the deficiency

Disturbed absorption

Lack of intrinsic factor

This factor deficiency occurs either as a result of type A gastritis , (a A utoimmungastritis , wherein antibodies against the parietal cells, and the intrinsic factor are directed), which is a chronic inflammation of the gastric mucosa, or by removal of the stomach portion ( gastrectomy ), in which the intrinsic factor is formed, i.e. the corpus and fundus. A Type B gastritis typically does not cause vitamin B12 deficiency to, since usually the antrum is affected.

Reduced supply in the intestine

  • due to increased vitamin B 12 consumption by parasites in the intestine ( worms )
  • reduced content in the diet, e.g. B. Alcoholism

Symptoms

The combination and severity of the symptoms can vary from case to case.

The (primary form of) adrenal insufficiency (also called Addison's disease), which has similar symptoms to pernicious anemia (also called addisonian anemia ), was initially confused with this by Thomas Addison.

Anemic symptoms

The typical complaints are tiredness, reduced performance, increased heart rate, paleness and a tendency to collapse as a result of anemia. Further, a is jaundice (yellowing of the skin) observed an inflammatory erythematous, "smooth" tab ( atrophic or Hunter glossitis : fire red, sunken spots or stripes, surrounded by bright, violet gray areas with unchanged or missing Papillenzeichnung; atrophy may proceed and lead to extensive or complete loss of the papillae of the tongue, the so-called mirror tongue), indigestion and abdominal pain.

Neurological symptoms

Neurological symptoms often appear with no evidence of anemia. These appear as abnormal sensations or numbness of the skin (tingling, furry feeling), hands and feet falling asleep, unsteady gait, coordination disorders or, more rarely, paralysis. The full picture of these symptoms caused by demyelinating spinal cord degeneration is called funicular myelosis . Visual disturbances or a picture of a polyneuropathy are also possible. Finally, psychological symptoms such as poor memory, poor concentration, depression and psychosis ( “megaloblastic madness” ) as well as schizophrenia and dementia have been described.

diagnosis

The diagnosis is confirmed by laboratory tests:

Laboratory examination

Safe test

additionally to test:

New test

Supportive tests
(high risk of false (negative and positive) results)

  • Methylmalonic acid in the blood (not applicable to kidney disease and dehydration)
  • Indication of anemia if the blood count shows the typical macrocytic-hyperchromic anemia . (A few large red blood cells loaded with a lot of hemoglobin; see also erythrocyte distribution range .) Folic acid can make the blood count appear "normal" despite a B 12 deficiency. Neurological damage often occurs before the signs of anemia in the blood.
  • Indication of impaired absorption of vitamin B 12 by the intestine with the help of the Schilling test (ingestion of radioactively marked vitamin B 12 , which then appears in the urine when absorbed). Risk of false normal values, as some can ingest crystalline B 12 , but not food-bound B 12 .

In the search for causes a gastroscopy (is gastroscopy ) with sampling (steps biopsy) for the detection of atrophic gastritis usual. Stool examinations with cultures for microorganisms and tests for worm eggs can also be carried out. However, gastroscopy cannot rule out a B 12 deficiency.

A physical including neurological examination is part of the diagnosis.

Anti-parietal cell autoantibodies

In the autoimmune form of vitamin B-12 deficiency, only about 60% have anti- parietal cells - autoantibodies directed against the a and b subunits of the gastric H + / K + -ATPase. The H + / K + -ATPase is an enzyme that transports hydrogen ions and is necessary for the formation of gastric acid (“ proton pump ”). The H + / K + -ATPase belongs to the electronically neutral ion pumps.

Blood count

Pernicious anemia can exist without changes in the blood count. As a result of a deficiency, the number of red blood cells ( erythrocytes ) decreases ; In addition, they appear too large and contain more hemoglobin per cell , because cell division is disrupted in the immature precursor cells of the red blood cells in the bone marrow . In the microscopic examination, so-called megaloblasts (very large precursor cells) and megalocytes (very large erythrocytes) are found. As it progresses, the formation of white blood cells ( leukocytes ) and blood platelets ( thrombocytes ) is also impaired.

in megaloblastic anemia:

  • Blood count, microscopic differential blood count (oversegmented neutrophils?), Reticulocytes
  • CRP, LDH, bilirubin, ASAT (GOT), ALAT (GPT), AP, γ-GT, electrolytes
  • Vitamin B 12 , folic acid, ferritin concentration in the serum
  • if the constellation of findings is unclear: bone marrow examination

Folate metabolism / folic acid

Elevated blood values ​​of methyl malonate and homocysteine are a very sensitive indication of a disorder of the folate metabolism and can be used for differential diagnosis in patients with neurological changes in whom the changes in the blood count and vitamin concentrations are only marginally changed. Folic acid can mask a B 12 deficiency in the blood count.

Differential diagnostics

General risk groups:

  • Vegetarians and vegans , especially their children and breastfeeding children
  • Seniors from approx. 60 years

Diseases that can cause a deficiency:

treatment

If the cause cannot be eliminated, vitamin B 12 must be supplied for life. In this case, B 12 must be administered in very high doses of at least 1000 µg. The first commercially available drug for the treatment of pernicious anemia with vitamin B 12 as the main active ingredient was the extract Campolon from Bayer AG , obtained from the livers of slaughtered animals , which remained on the market until around 1970.

In the case of chronic inflammation of the gastric mucosa, it is injected into the muscles or subcutaneously (also if the stomach has been completely or partially removed). In cases where a deficiency in the intrinsic factor can be diagnosed, it can be given to correct the malabsorption. In chronic atrophic gastritis of type A, there is the possibility of treating the initial signs of inflammation and changes in the mucous membrane with cortisone.

Therapy with vitamin B 12 in the form of methyl cobalamin and adenosylcobalamin promises the greatest success. In a typical therapy, 1000 µg are injected daily up to three times a day for the first few weeks, then further injections of approx. 1000 µg are administered every one to two months for life.

Oral therapy (tablets): Contrary to popular belief, oral therapy (tablets) also promises to be successful. With an absorption of approx. 1%, absorption is possible even without an intrinsic factor. A minimum dose of 500 µg must be observed here in order to enable absorption. In order to achieve comparable results, a daily dose of at least 1000 µg is required. In any case, it is important to check the values ​​regularly.

Web links

Individual evidence

  1. ↑ Ludwig Heilmeyer , Herbert Begemann: Blood and blood diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition ibid. 1961, pp. 376–449, here: pp. 410–415 ( Die pernicious anemia ).
  2. ↑ Habermehl, Hammann, Krebs: Naturstoffchemie. An introduction. 2nd Edition. Springer, Berlin 2002, ISBN 3-540-43952-8 .
  3. ↑ E. Andres: Vitamin B12 (cobalamin) deficiency in elderly patients . In: Canadian Medical Association Journal . tape 171 , no. 3 , August 3, 2004, ISSN  0820-3946 , p. 251-259 , doi : 10.1503 / cmaj.1031155 .
  4. ↑ Errata for Rubin LG et al (Clin Infect Dis 2014; 58: 309-318) . In: Clinical Infectious Diseases . tape 59 , no. 1 , June 12, 2014, ISSN  1058-4838 , p. 144-144 , doi : 10.1093 / cid / ciu256 .
  5. ↑ Ludwig Weissbecker : Diseases of the adrenal cortex. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition, ibid. 1961, pp. 1013-1025, here: p. 1016.
  6. ↑ Procedure for the determination of Transcobalamine II
  7. ↑ UMMA test
  8. ↑ SE Miederer: The Histotopographie the gastric mucosa . Thieme, 1977, ISBN 3-13-508601-1 .
  9. ↑ American Family Physician: B 12 Deficiency, 2003
  10. ↑ Cervical Funicular Myelosis, 2005
  11. ↑ Oral vitamin B 12 substitution in funicular myelosis (cervical spine) University Hospital Bonn 2006
  12. ↑ Parkinson's, B 6 , B 12 , and Folate - What's the Connection?
  13. ↑ P. Marko, F. Marty: Vitamin B12 and skin diseases . In: PrimaryCare , 2006, 6, pp. 434-436.
  14. ↑ American Family Physician: B 12 Deficiency, 2003
  15. ↑ Oral vitamin B 12 substitution in funicular myelosis (cervical spine) University Hospital Bonn 2006