Pernicious Anemia

Pernicious anemia, a form of megaloblastic anemia, is a rare disorder in which the body does not absorb enough vitamin B12 from the digestive tract, resulting in an inadequate amount of red blood cells (RBCs) produced.

Pernicious anemia is one of many different types of anemia. Having anemia means that there are not enough healthy red blood cells, or that the cells cannot carry oxygen efficiently. When a person has anemia, the blood cannot carry enough oxygen to the cells of the body. The most common symptom of anemia is feeling tired.

Other Names

• Vitamin B12 deficiency anemia
• Combined systems disease
• Congenital pernicious anemia
• Addisonian anemia
• Biermer's anemia
• Addison-Biermer anemia
• Addison's anemia (named after the physician Thomas Addison who first described the condition in 1855)

Addison anemia was renamed pernicious anemia in 1872 by the German physician Anton Biermer (hence some of the other names). He is said to have provided a better description of the illness. At this time the disease was deadly, hence “pernicious.”

The taste buds on this tongue have atrophy giving the tongue a pale smooth appearance. This change is typical of a vitamin B12 deficiency. Source: CDC

Signs and Symptoms

Below are some major symptoms of pernicious anemia:

• feeling tired and weak
• a bright red and/or smooth tongue (see picture at right)
• nerve damage that causes tingling and numbness in the hands and feet (neuropathy)

Symptoms usually develop slowly over time if the disease is not treated. Some people may experience mental changes and nerve problems before blood tests show that they have anemia. This is more likely to happen in older adults than in younger people.

Other symptoms of pernicious anemia include the following:

• pale or yellowish skin
• low-grade fever
• dizziness when standing up
• infants with the condition may show unusual movements or a delayed development and failure to thrive.

Causes

Pernicious anemia most commonly results from the loss of parietal cells in the lining of the stomach. Without these cells, there is a lack of production of intrinsic factor in gastric secretions (a substance needed to absorb vitamin B12 from the gastrointestinal tract). The result is a vitamin B12 deficiency.

The inability to make intrinsic factor may be the result of chronic gastritis, or the result of a gastrectomy (removal of all or part of the stomach). Megaloblastic (pernicious) anemia may also be associated with type 1 diabetes, thyroid disease, and a family history of the disease.

In some people, the body's immune system may attack and destroy the parietal cells. Doctors don't know exactly why or how this happens, or if the immune system produces antibodies in reaction to normally aging or dying parietal cells. As a result of this immune system attack, the stomach lining shrinks, and the parietal cells disappear. The stomach stops producing intrinsic factor. Over time, vitamin B12 deficiency develops.

In addition, a rare, inherited disorder results in the inability to produce intrinsic factor. This is called congenital pernicious anemia.

Other causes

Less common causes of pernicious anemia include a diet low in vitamin B12, intestinal problems, and certain medicines.

Vitamin B12 deficiency

Pernicious anemia can develop if a person’s diet lacks vitamin B12. In this case, the anemia develops over many years because it takes time to use up the vitamin B12 already stored in the body.

Some strict vegetarians can develop pernicious anemia because they do not eat meat, poultry, or fish. These foods, along with eggs and dairy products, are the best sources of vitamin B12. Breastfed infants of strict vegetarian mothers can develop anemia in a short time because they don't have enough vitamin B12 stored in their bodies. They can be given vitamin B12 supplements to prevent this type of anemia.

Some people develop pernicious anemia because of a poor diet due to conditions such as alcoholism or aging.

Disorders of the small intestine

Some intestinal problems can cause poor absorption of vitamin B12:

• Infections caused by parasites or an overgrowth of bacteria in the intestine
• Celiac disease (also known as sprue), a genetic disorder that makes a person unable to tolerate gluten. Gluten is a type of protein that provides elasticity to breads and give them their familiar texture.
• Crohn's disease, an inflammatory bowel disease
• Reduced stomach acidity (low amount of stomach acid) that is insufficient to digest food. This frequently occurs in the elderly.

Medicines

Long-term use of certain medicines may also lead to pernicious anemia. Examples of these are medicines that reduce acid in the stomach and certain diabetes medicines (such as metformin (Glucophage), phenformin (Fenormin), and biguanides).

Risk Factors

People of all races can develop pernicious anemia. However, people of northern European or African descent have a higher risk than other races and ethnic groups.

Men and women in the United States are equally likely to develop the disease. It is more common in older adults than younger people, and it is rare in children.

Major risk factors

The risk of developing pernicious anemia increases in the following conditions:

• A family history of pernicious anemia
• A disorder such as diabetes or a thyroid problem
• An intestinal disorder that keeps the body from absorbing vitamin B12 well

Pernicious anemia is more likely to develop in people who do not eat foods high in vitamin B12 for long periods of time. This includes some vegetarians, elderly people, and alcoholics.

Complications

Complications seen with pernicious anemia can involve the heart, nerves and brain, and digestive tract. Some of the complications are due to the anemia itself, whereas others develop due to the lack of vitamin B12.

Heart. In anemia, the heart has to work harder to pump blood to get enough oxygen to the body’s organs and 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.

A lack of vitamin B12 or folic acid (folate) can cause extra problems for the heart because it raises levels of homocysteine. High levels of homocysteine add to the buildup of fatty deposits in blood vessels, which in turn can lead to heart attacks and strokes.

Nerves. A lack of vitamin B12 can damage nerve cells and cause problems such as tingling and numbness in the hands and feet and problems with walking and balance. A vitamin B12 deficiency can cause changes in taste, smell, and vision. Finally, it can cause mental changes, including memory loss and confusion.

Digestive tract. A lack of vitamin B12 may change the surface of the tongue and shrink or thin the stomach lining. The liver may become enlarged. Nausea and vomiting may occur, along with a sense of fullness, gas, or heartburn. Constipation or diarrhea may also occur. As a result, loss of appetite and/or weight loss may be seen. Changes that occur in the stomach can put a person at risk for stomach cancer.

Diagnosis

Pernicious anemia is diagnosed using a person's medical history, physical exam, and tests that can determine the type and cause of anemia. Doctors use these methods to find out how severe the problem is, its cause, and the appropriate treatment. Mild to moderate anemia may have no signs or symptoms. In fact, anemia is often discovered unexpectedly on screening tests.

Specialists involved

Primary care doctors, such as a family doctor, often diagnose and treat pernicious anemia. In some cases, other kinds of doctors become involved:

• neurologist (nervous system specialist)
• cardiologist (heart specialist)
• hematologist (blood disease specialist)
• gastroenterologist (digestive tract disease specialist)

Medical and family history

A doctor looks for symptoms, especially if there is a feeling of being tired and weak. She may ask about any personal or family history of anemia, diabetes, or diseases of the immune system. Surgeries, especially stomach surgery, are noted. The doctor also takes into account diet and medications.

Physical exam

Physical exams can reveal symptoms:

• Checking for pale or yellowish skin and a red, smooth tongue
• Listening to the heart to check for a rapid heartbeat or heart murmur
• Feeling the abdomen to check the size of the liver

Other tests and procedures can be performed to determine the severity and type of anemia.

Diagnostic tests and procedures

Diagnostic tests take samples of blood, urine, or bone marrow to examine vitamin B12 levels as well as other markers of anemia.

Complete blood count

Usually, the first test used to diagnose anemia is a complete blood count (CBC). The CBC tells a number of things about a person’s blood:

• Hemoglobin level - Hemoglobin is the iron-rich protein in red blood cells that carries oxygen through the body. Low hemoglobin levels can suggest anemia.
• Hematocrit level - The hematocrit measures how much of the blood is made up of red blood cells. Low hematocrit is another sign of anemia.
• The number of red blood cells - Too few red blood cells means a person has anemia. A low number of red blood cells is usually seen with either a low hemoglobin or a low hematocrit level, or both.
• The number of white blood cells - White blood cells are involved in fighting infection.
• The number of platelets in the blood - Platelets are small cells that are involved in blood clotting.
• Red blood cell size - The mean cell volume measures the average size (volume) of red blood cells. In pernicious anemia, the red blood cells are usually larger than normal. This is called macrocytosis.

Tests to check vitamin B12 level

Blood tests are also used to evaluate the amount of Vitamin B12 in the body, either by measuring vitamin B12 directly or by using surrogate markers.

• The level of vitamin B12 in the bloodstream may be normal or borderline even when the total amount of B12 in the body is low.
• Folic acid (folate) is another B vitamin that can be low when the B12 level is low. A lack of folic acid also cause anemia.
• Homocysteine is high in anemia due to the lack of vitamin B12 or folic acid. Folate deficiency is more common because this vitamin is used up more quickly and the dietary need is greater. In this case, the blood’s B12 level can be normal.
• The level of methylmalonic acid is high in anemia due to a lack of vitamin B12 or folic acid. Methylmalonic acid can also be checked with a urine test.

Other blood tests

Other blood tests are used to check for the following:

• Intrinsic factor antibodies and parietal cell antibodies. These antibodies may be destroying the intrinsic factor or parietal cells.
• Bilirubin, potassium, or cholesterol
• Serum iron and iron binding capacity
• Reticulocytes. Reticulocytes are young, red blood cells. The reticulocyte test is used to see if the bone marrow is producing red blood cells at the proper rate. A lower than average number of reticulocytes can mean that the bone marrow is not making enough red blood cells. The reticulocyte number is low in people with pernicious anemia.

Schilling test

The Schilling test is a urine test that measures how well the body absorbs vitamin B12. It has largely been phased out in favor of the blood tests.

Bone marrow tests

In some cases, a doctor performs a Bone Marrow_bone marrow biopsy or aspiration. A bone marrow biopsy is a minor surgical procedure to remove a small amount of bone marrow. In a bone marrow aspiration, the doctor removes a small amount of bone marrow fluid with a needle. Bone marrow biopsy or aspiration tests whether the bone marrow is healthy and can show whether the bone marrow is making enough blood cells.

Treatment

Doctors treat pernicious anemia by replacing the missing vitamin B12 in the body. Often lifelong treatment is necessary. Without treatment, pernicious anemia can cause serious problems and can even be fatal.

Treatment of pernicious anemia has several goals:

• Stop the anemia and symptoms using vitamin B12 supplementation
• Prevent complications, such as heart or nerve damage
• Provide ongoing follow-up to make sure that the treatment is working
• Treat the underlying cause, if one can be found

Specific types of treatment

Fortunately, pernicious anemia is usually easy to treat with either vitamin shots (injections) or pills. Symptoms may begin to improve within a few days after the start of treatment.

• Vitamin B12 shots. Injections are initially given daily or weekly, then monthly. Sometimes the injections are used in combination with vitamin B12 supplements.

Vitamin B12 pills. Many people with pernicious anemia can be treated successfully with vitamin B12 pills. Often, the pills work as well as the shots. High doses are given because only a small amount of vitamin B12 is absorbed by the body.

Vitamin B12 can also be given in a gel or spray to be administered into the nose.

Treatment of the underlying cause of the pernicious anemia may be required. To help the body absorb vitamin B12, for example, antibiotics to treat stomach infections or surgery to treat intestinal problems can be used. Improvements in the diet can replenish low vitamin B12 stores in the body.

Sometimes physical activity needs to be limited during anemia.

Prevention

Pernicious anemia due to an immune attack against parietal cells cannot be prevented. Most cases are caused by this or other conditions that destroy these stomach cells and prevent the production of intrinsic factor.

Eating foods high in vitamin B12 and folic acid can help prevent low vitamin B12 levels. Below are some good dietary sources of these vitamins:

• Eggs, meat, poultry, or shellfish
• Milk, orange juice, or oranges
• Fortified cereals, wheat germ, rice, or barley
• Romaine lettuce, spinach, and other green leafy vegetables
• Sprouts, broccoli, asparagus
• Peas, peanuts, beans, lentils, soy beans, and chickpeas

Vitamin B12 is also found in multivitamins and in B-complex vitamin supplements. Supplements are frequently used in people who are at risk of developing vitamin B12 deficiency, such as infants and children of strict vegetarians.

Living with Pernicious Anemia

People treated for pernicious anemia can recover, feel well, and live normal lives, although they must be sure to receive enough vitamin B12 throughout their lives. Treatment can often reverse complications caused by the anemia, such as nerve damage.

Ongoing health care needs

People with pernicious anemia usually need to see a doctor regularly for checkups and ongoing treatment with vitamin B12. Vitamin B12 supplements can help prevent the return of symptoms.

Doctors continue to monitor people with vitamin B12 to check for new symptoms and stomach cancer, as well as to adjust treatment. They also monitor diet. Continued treatment may be needed for any ongoing problems due to nerve damage.

Family members

Awareness of the condition by all family members, especially children and siblings, helps diagnosis and outcome because pernicious anemia runs in families.

Prevalence

The prevalence of pernicious anemia in the general population is not known. A study of Americans over the age of 65 years found that the prevalence of low vitamin B12 detected in the blood was 15%.^[1] However, this is probably an underestimate considering the rising population of the elderly and the widespread use of drugs that reduce stomach acidity.^[2]

Interesting Facts

• The inventor Alexander Graham Bell had pernicious anemia.

• Eating liver was the first successful treatment for pernicious anemia. The physicians who discovered this treatment won a Nobel Prize.

References

1. ↑ Pennypacker LC, Allen RH, Kelly JP, et al. High prevalence of cobalamin deficiency in elderly outpatients. J Am Geriatr Soc. 1992 Dec;40(12):1197-204. Abstract
2. ↑ Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician. 2003 Mar 1;67(5):979-86. Abstract | Full Text | Summary for Patients

External Links

National Institutes of Health, Office of Dietary Supplements: “Dietary Supplement Fact Sheet: Vitamin B12”

Pernicious Anaemia: One personal experience: Pernicious Anaemia