Pernicious anemia is a decrease in red blood cells that occurs when the body cannot properly absorb vitamin B12 from the gastrointestinal tract. Vitamin B12 is necessary for the proper development of red blood cells.

Pernicious anemia is a type of megaloblastic anemia.

See also: Anemia

Pernicious anemia is caused by a lack of intrinsic factor. Intrinsic factor is a protein produced by the stomach that binds to vitamin B12. The combination of vitamin B12 and intrinsic factor is absorbed in the lower part of the small intestine. When the stomach does not make enough intrinsic factor, the intestine cannot properly absorb vitamin B12.

Very rarely, infants and children are born without the ability to produce enough intrinsic factor. Pernicious anemia that occurs at birth (congenital) is inherited. You need the defective gene from each parent to get it.

More common causes of pernicious anemia include:

• Weakened stomach lining (atrophic gastric mucosa)
• The body's immune system attacking the cells that make intrinsic factor (autoimmunity against gastric parietal cells)
• Autoimmunity against intrinsic factor itself

The disease begins slowly and may take decades to fully establish. Although the congenital form occurs in children, pernicious anemia usually does not appear before age 30 in adults. The average age at diagnosis is 60.

Risk factors include:

• Family history of the disease
• History of autoimmune endocrine disorders, including:
  • Addison's disease
  • Chronic thyroiditis
  • Graves disease
  • Hypoparathyroidism
  • Hypopituitarism
  • Myasthenia gravis
  • Secondary amenorrhea
  • Type 1 diabetes
  • Testicular dysfunction
  • Vitiligo
• Scandinavian or Northern European descent

In addition to pernicious anemia, other causes of vitamin B12 deficiency include:

• Certain drugs, including colchicine, neomycin, and para amino salicylic acid (used for tuberculosis treatment)
• Gastrointestinal disease (stomach removal surgery, celiac disease, Crohn's disease)
• Infection (intestinal parasites, too much growth of bacteria in the small intestine)
• Metabolic disorders (methylmalonic aciduria, homocystinuria)
• Nutritional problems (strict vegetarians who do not get vitamin B12 supplementation, poor diet in infancy, or poor nutrition during pregnancy)

Too little vitamin B12 gradually causes nervous system (neurological) problems. The neurological effects may be seen before anemia is diagnosed.

Symptoms may include:

• Bleeding gums
• Diarrhea
• Fatigue
• Impaired sense of smell
• Loss of deep tendon reflexes
• Loss of appetite
• Pallor
• Personality or memory changes
• Positive Babinski's sign
• Rapid heart rate
• Shortness of breath
• Sore mouth
• Tingling and numbness of hands and feet
• Tongue problems
• Unsteady gait, especially in the dark

Tests that may used to diagnose or monitor pernicious anemia include:

• Bone marrow examination (only needed if diagnosis is unclear)
• Complete blood count
• Measurement of serum holotranscobalamin II
• Reticulocyte count
• Schilling test
• Serum LDH
• Serum methylmalonic acid (MMA) level
• Serum vitamin B12 level

Pernicious anemia may also alter the results of the following tests:

• Bilirubin
• Cholesterol test
• Gastrin
• Leukocyte alkaline phosphatase
• Peripheral smear
• TIBC

Vitamin B12 deficiency affects the appearance of cells that form on the outer surface of the body and line inner passageways (epithelial cells). An untreated woman may have a false positive Pap smear.

Monthly vitamin B12 injections are prescribed to correct the vitamin B12 deficiency. This therapy treats the anemia and may correct the neurological complications if taken early enough. In people with a severe deficiency, the injections are given more frequently at first.

Some doctors recommend that elderly patients with gastric atrophy take vitamin B12 supplements by mouth in addition to monthly injections.

There is also a preparation of vitamin B12 that may be given through the nose. For some people, taking vitamin B12 by mouth in a very high dose can also be an effective treatment.

A well-balanced diet is essential to provide other elements for healthy blood cell development, such as folic acid, iron, and vitamin C.

The outcome is usually excellent with treatment.

People with pernicious anemia may have gastric polyps and they are at increased risk for gastric cancer and gastric carcinoid tumors.

Neurological defects may continue if treatment is delayed.

Call your health care provider if you have symptoms of vitamin B12 deficiency.

There is no known way to prevent this condition. However, with early detection and treatment of vitamin B12 deficiency, complications can be minimized.

Antony AC. Megaloblastic anemias. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007: chap 170.