Pernicious Anemia (Vitamin B12 Deficiency)

• Pernicious anemia is a type of anemia (reduced number of red blood cells or hemoglobin in the body) due to the body's inability to absorb vitamin B12 from the gastrointestinal tract.
• Symptoms from anemia are a result of the decreased capacity of the blood to carry oxygen and include fatigue and shortness of breath. In addition, the deficiency of vitamin B12 also can damage the nervous system.
• Vitamin B12 is also known as cobalamin (Cbl). Animal products, both meat and dairy, are the only dietary sources of vitamin B12 for humans. Because the body has stores of vitamin B12, inadequate dietary intake must persist for years before a true deficiency of vitamin B12 occurs.
• For this reason, the pernicious anemia usually takes years to establish and is most commonly diagnosed in adults with an average age of 60.
• Also, a rare, form of pernicious anemia called congenital pernicious anemia is present at birth.
• Pernicious anemia is a form of megaloblastic anemia. Megaloblastic anemia is characterized by abnormally large red blood cells (megaloblasts) formed by the bone marrow when vitamin B12 or folic acid levels are low.
• Megaloblastic anemia can also develop with other conditions that affect the bone marrow and as an effect of some chemotherapy drugs.
• Bacterial overgrowth in the gastrointestinal tract can also cause a lack of B12.

The decreased absorption of vitamin B12 from the gastrointestinal tract in pernicious anemia is believed to result from an autoimmune process in which the body's immune system attacks the lining of the stomach. Antibodies are produced against intrinsic factor (IF), a protein made in the stomach that is necessary for the absorption of vitamin B12. Normally, vitamin B12 binds to intrinsic factor in the stomach, and this facilitates its absorption later when digestive products pass through the small intestine. The autoimmune process attacks the IF protein and lowers IF levels in stomach secretions. An autoimmune process directed at the stomach lining cells also occurs and results in a chronic form of stomach inflammation (gastritis) known as chronic atrophic gastritis.

Pernicious anemia is more common in Caucasian persons of northern European ancestry than in other racial groups. Pernicious anemia may occur in association with other autoimmune diseases such as autoimmunethyroid disease and vitiligo.

While pernicious anemia is defined as anemia resulting from inadequate absorption of vitamin B12 from the gastrointestinal tract due to the autoimmune process described above, other causes of vitamin B12 deficiency can also produce the characteristic signs and symptoms of pernicious anemia. Other potential causes of vitamin B12 deficiency include surgical removal of the stomach or a portion of the stomach (gastrectomy), other gastrointestinal diseases such as celiac disease or Crohn's disease, infection, and poor nutrition.

Because the body has large stores of vitamin B12, a deficiency takes many years to establish so symptoms only develop after years of poor absorption of dietary vitamin B12.

Symptoms relating to the effects of vitamin B12 deficiency on the nervous system may appear before symptoms related to anemia. These symptoms may be vague and nonspecific, especially at the outset.

• Feelings of numbness,
• tingling,
• weakness,
• lack of coordination,
• clumsiness,
• impaired memory, and
• personality changes may be apparent.
• The legs are typically more affected than the arms, and usually both sides of the body are affected. When the deficiency is severe, symptoms can worsen, leading to severe weakness, spasticity, paraplegia, and fecal and urinary incontinence.

Importantly, not all people who have vitamin B12 deficiency and neurological symptoms will have anemia. However, when anemia is present, the typical symptoms of anemia may occur. When red blood cell numbers are reduced from anemia, the heart has to work harder to pump blood to get enough oxygen to the body's tissues.

• This stress on the heart can cause heart murmurs (an extra or unusual sound heard during the heartbeat),
• fast or irregular heartbeats,
• an enlarged heart, or even heart failure.
• Shortness of breath, fatigue, dizziness, and pale skin are other symptoms of anemia.

A deficiency of vitamin B12 can also alter the surface of the tongue, making it appear shiny or smooth.

In some cases, pernicious anemia may be present and not cause any symptoms. In this situation, it is usually found incidentally when blood tests are ordered for another reason.

• It is appropriate to seek medical care if a person has any of the neurological symptoms described above or any of the symptoms of anemia.
• All of the symptoms of pernicious anemia can be caused by a number of other conditions, and it is important to identify the exact cause of a person's symptoms to ensure proper and effective treatment.

As with any medical problem, the first step in the evaluation is a thorough history and physical examination. Other diagnostic tests that can help establish the diagnosis of pernicious anemia or rule out other causes of the symptoms include:

• a complete blood cell count (CBC) to establish whether anemia is present and to further characterize the type of anemia;
• examination of a blood smear (peripheral smear) under a microscope, often performed in association with a CBC;
• other blood tests, for example tests to measure vitamin B12 levels, auto-antibodies to IF or to stomach lining cells (parietal cells), blood iron and iron-binding capacity levels, folate levels (which can also be low when vitamin B12 levels are low);
• tests to measure blood levels of methylmalonic acid (MMA) or homocysteine, both of which may be sensitive indicators of vitamin B12 deficiency;
• an elevated MMA level is seen with B12 deficiency, whereas elevated homocysteine levels are characteristic of both B12 and folate deficiencies;
• bone marrow aspiration or bone marrow biopsy may be recommended in some cases to examine for the presence of bone marrow disorders.

• Pernicious anemia can be treated by replenishing the vitamin B12 supply in the body.
• If another underlying condition is responsible for vitamin B12 deficiency, treatment must also be directed at that underlying process.

Be sure to follow the doctor's recommendations concerning diet and physical activity, and take all medications exactly as prescribed.

• Medical treatment is the mainstay of treatment for pernicious anemia and consists of vitamin B12 preparations to replenish vitamin B12 stores.
• Medical treatment is generally very effective, and symptoms may be improved with a few days of starting treatment.

• Pernicious anemia is typically treated with an intramuscular injection of 1000 micrograms (1 mg) of vitamin B12 every day for one week, followed by 1 mg every week for four weeks and then 1 mg every month thereafter.
• Alternative treatments include high-dose oral vitamin B12, since a lower-efficiency absorption system for vitamin B12 exists in the intestine that does not require the presence of IF. The dose required (1 to 2 milligrams/day) is more than 200 times higher than the minimum daily requirement for adults and is significantly higher than that available in most standard multivitamins and B12 supplements. Nasal spray and sublingual (under the tongue) preparations of vitamin B12 are also available.

• The doctor will determine how often follow-up visits and blood tests are necessary for a patient's specific situation.
• As mentioned above, follow-up visits for the administration of vitamin B12 injections are generally necessary.

• Pernicious anemia develops as a result of an autoimmune process in the body and cannot be prevented. The effects of pernicious anemia can be prevented by replacing the B12 in the body.
• Other causes of vitamin B12 deficiency, such as other gastrointestinal diseases and gastrointestinal surgery, are preventable only to the extent that these causes themselves are preventable. Vitamin B12 deficiency in vegetarians can be prevented by the use of vitamin B12 supplements. An oral dose of 100-200 micrograms (mcg) taken weekly should be sufficient.

• Pernicious anemia is easily and effectively treated by the administration of vitamin B12. Lifelong treatment is required.
• If untreated, the neurological complications of pernicious anemia can be permanent. The incidence of stomach cancer in people with pernicious anemia is 2-3 times higher than in the general population of the same age.