What Is Pernicious Anemia?

Pernicious anemia is an autoimmune condition in which the body can’t absorb vitamin B12 correctly. This leads to symptoms from anemia (a reduced number of functioning red blood cells) and other problems. The word “pernicious” means gradually harmful and damaging. Historically, before we understood its role and had vitamin B12 treatments available, it was often fatal.

Pernicious anemia is also sometimes referred to as “autoimmune gastritis” or “Biermer’s disease.” It is more common in older adults, and it is estimated to affect around 2% of adults over the age of 60.

Pernicious Anemia Symptoms

Symptoms often come on gradually and are mild at first but may worsen if untreated. For example, mild fatigue might be an initial sign. Other symptoms of pernicious anemia can include the following:

• Pale skin
• Weakness of the arms and legs
• Tingling or prickling of the skin
• Shortness of the breath
• Dizziness
• Racing heartbeat
• Abdominal bloating
• Diarrhea
• Weight loss
• Swelling of the extremities
• Darkened skin
• Poor balance
• Forgetfulness and poorer overall cognitive function

If pernicious anemia isn’t treated for a long period of time, these cognitive problems can get even worse, possibly causing psychosis or dementia. In extreme circumstances, it can cause significant problems with the nervous system and even death.

People with pernicious anemia also have a much higher than average likelihood of having other autoimmune conditions, which might emerge before or after symptoms of pernicious anemia. For example, they have a higher risk of having type 1 diabetes, autoimmune thyroid disease, and vitiligo. These may cause additional, distinct symptoms.

People with pernicious anemia also have an increased risk of developing some types of stomach cancer, including gastric carcinoid tumors and adenocarcinomas.

Causes

The most common cause of pernicious anemia is autoimmune gastritis leading to vitamin B12 deficiency. Rarely, there is a genetic or congenital cause. There are also other conditions resulting in poor absorbtion or low vitamin B12.

Vitamin B12 Deficiency Due to Autoimmune Gastritis

The symptoms of pernicious anemia occur because it leads to a deficiency in vitamin B12 (also known as “cobalamin”).

Vitamin B12 is important for many different chemical reactions in the body. It performs several important functions, including helping with the synthesis of DNA. It plays a key role in the brain and nervous system, and it’s also necessary for production of healthy red blood cells. So, it’s not surprising that symptoms result when there isn’t enough vitamin B12 in the body.

Vitamin B12 must be taken in through the diet through foods of animal origin. Some of the cells lining the inside of the stomach make a special protein, called intrinsic factor, that binds to vitamin B12. It helps transport the vitamin to the small intestine, where it can be absorbed into the blood and eventually be utilized by the body.

In pernicious anemia, something affects the body’s ability to effectively make intrinsic factor. Because of autoimmune gastritis (the underlying cause of pernicious anemia) the body’s immune system is abnormally activated.

Antibodies form against intrinsic factor and the cells that make it, causing inflammation in the stomach. Due to this inflammatory process, the cells of the stomach don’t make as much intrinsic factor as they should, and not enough vitamin B12 gets absorbed by the body, leading to the symptoms of pernicious anemia.

Researchers are still learning why this happens to some people. Having variations of certain genes important for the immune system may increase its likelihood, and you might have greater risk if someone else has had it in your family. The risk also increases with age.

Other Causes of Vitamin B12 Deficiency

Although the symptoms of pernicious anemia are caused by vitamin B12 deficiency, it is not the only possible cause of such a deficiency. This can be caused by other situations, including ones that decrease effective absorption of vitamin B12.

Potential causes include Crohn’s disease, parasitic infection, poor dietary intake (e.g., in someone with a vegan diet), medication side effects (like from metformin), or as a side effect of certain surgeries done on the gastrointestinal tract. Pernicious anemia is estimated to be the underlying cause of vitamin B12 deficiency around 20% to 50% of the time.

Extremely rarely, pernicious anemia can be caused by a genetic condition, in which the body can’t make intrinsic factor normally. This type is called “congenital pernicious anemia” or “intrinsic factor deficiency.” Unlike the more common form, symptoms usually begin in childhood.

Diagnosis

It’s important for clinicians to rule out other potential causes of your symptoms, including different issues that might lead to vitamin B12 deficiency.

The medical history provides the starting point for diagnosis. The clinician asks about recent symptoms, long-term medical issues, and other relevant topics.

For example, your healthcare provider may ask you if you have another autoimmune medical condition, or if you’ve had had surgery in the gastrointestinal tract (such as for weight loss). A physical exam provides additional key initial information, like information about how the nervous system is functioning.

Basic laboratory studies can help point to possible deficiency of vitamin B12. A test called a complete blood count (CBC) can often provide some key clues.

In someone with pernicious anemia, these tests can show a reduced number of functioning red blood cells in the body. For example, low hemoglobin—the protein that carries oxygen—can be a sign of anemia. Low hematocrit, which shows the amount of space the red blood cells take up in the blood, can also be a sign.

In people with pernicious anemia, the red blood cells are also larger than normal, as measured by a test called the mean corpuscular volume (also performed as part of a CBC).

Depending on the situation, you might need additional tests to determine the cause of the anemia, although not everyone will need all these tests. Potential blood tests might include:

• Vitamin B12
• Reticulocyte count
• Iron tests
• Antibody tests for intrinsic factor
• Methylmalonic acid and/or homocysteine (may be elevated in pernicious anemia)
• Gastrin (may be elevated in pernicious anemia)

Another older test, the Schilling test, is now rarely performed.

Pernicious anemia may be harder to detect in someone who is iron deficient. That’s because the iron deficiency can cause a different type of anemia which makes the red blood cells smaller, not bigger.

A person might be deficient in both iron and B12, perhaps because of very poor diet or problems with absorption from autoimmune gastritis. This makes interpretation a little more difficult.

Unfortunately, diagnosis can sometimes be tricky, because the standard tests can’t always be relied upon for straightforward interpretation. Sometimes it’s helpful to get another test, an endoscopic biopsy of the stomach, if a diagnosis is in question.

It’s critical the clinicians consider the possibility of pernicious anemia, because treatment with vitamin B12 can dramatically improve symptoms, which can become life-threatening if they remain untreated.

Treatment

The treatment of pernicious anemia is straightforward. Affected people must take vitamin B12 to remedy their deficiency. This is often done as a series of injections into a muscle, with decreasing frequency over a period of months. Most people notice radical improvements in their symptoms within 24 hours, and the anemia itself starts to improve within the week.

Taking vitamin B12 orally is another option, although this is not recommended for people with serious neurological symptoms. In either case, you will need to start with a higher and/or more frequent dose. But you will probably need to take vitamin B12 for the rest of your life, either through monthly injections or daily oral treatment.

If you have pernicious anemia (and not just problems from not eating enough foods with vitamin B12), increasing your intake of B12 through the diet alone isn't usually enough to address the problem.

Prevention and Monitoring

Your healthcare provider also might recommend periodic endoscopy of your stomach, perhaps every three to five years. This procedure uses a long tube inserted inside your stomach to look for any signs of cancer. This can help ensure that any potential cancer could be detected and treated promptly.

Overall, it’s important to get long-term follow-up. Your practitioner can make sure you are still responding well to therapy and check for signs of related autoimmune disease.

A Word From Verywell

Once it’s diagnosed, dealing with pernicious anemia isn’t nearly as bad as it sounds. Work with your healthcare provider to make sure you get the long-term monitoring and follow-up that you need.