- Tingling in the hands and feet, trouble walking, or mental confusion can be signs that pernicious anemia is affecting the nervous system.
- Shortness of breath, heart palpitations, or extreme tiredness may suggest the anemia is becoming more severe.
- A smooth swollen tongue, sores at the corners of the mouth, or sudden dizziness and mood changes should not be ignored.
Pernicious anemia is a type of megaloblastic anemia in which the body does not have enough vitamin B12. This can cause symptoms such as weakness, paleness, fatigue, and tingling in the hands and feet.
Pernicious anemia, also called Addison’s anemia, happens mainly because the body lacks a protein needed to absorb vitamin B12 (cobalamin). Without this protein, vitamin B12 is not absorbed properly and is instead eliminated in the urine.
Pernicious anemia is diagnosed with laboratory tests, which may include measuring vitamin B12 levels in the urine. Treatment usually involves vitamin B12 and folic acid supplements, along with a healthy diet rich in vitamin B12.
Main symptoms
The main symptoms of pernicious anemia are:
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Weakness or extreme tiredness.
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Paleness.
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Headache, dizziness, irritability, and sudden mood changes.
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Diarrhea.
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A smooth, swollen tongue.
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A feeling of fullness in the stomach.
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Weak, brittle nails.
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Tingling in the hands and feet, or cold hands and feet.
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Heart palpitations.
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Sores at the corners of the mouth.
In more severe cases, pernicious anemia can affect the nervous system, which may lead to trouble walking, depression, and mental confusion.
Confirming a diagnosis
Pernicious anemia should be evaluated by a hematologist or primary care provider, starting with an assessment of symptoms and eating habits. Blood and imaging tests are usually needed to confirm the diagnosis.
A provider may order a complete blood count (CBC) to check the number of red blood cells and the amount of hemoglobin in the blood, along with the Schilling test, which measures how much vitamin B12 is excreted in the urine.
One imaging test that is often used when evaluating pernicious anemia is an upper endoscopy, because it can help identify stomach lesions.
A myelogram may also be requested to assess how the bone marrow is functioning. In pernicious anemia, this test may show large, immature erythroid precursor cells, although it is invasive and is rarely used to help diagnose anemia.
The Schilling test
The Schilling test is a lab test used to help confirm pernicious anemia. First, the person takes vitamin B12 by mouth with a special marker. Two hours later, they receive an injection of vitamin B12 without the marker. Then, urine is collected over the next 24 hours and analyzed.
If the test shows vitamin B12 in the urine, the test is repeated 3 to 7 days later with intrinsic factor given along with the oral vitamin B12. Another urine sample is then collected over 24 hours to see whether vitamin B12 is still being excreted.
If vitamin B12 is no longer found in the urine after intrinsic factor is added, the result supports a diagnosis of pernicious anemia. This means the body was able to absorb the vitamin once it received intrinsic factor, a protein it is not making properly on its own.
Possible causes
According to the NIH Office of Dietary Supplements, people with pernicious anemia do not make the intrinsic factor needed to absorb vitamin B12, which leads to poor absorption of the vitamin from food and supplements.
The most likely cause of pernicious anemia is immune-related. In this case, the immune system appears to attack the stomach lining, causing atrophy and chronic inflammation, which increases hydrochloric acid secretion in the stomach and decreases intrinsic factor production, reducing vitamin B12 absorption.
In addition to immune-related causes, pernicious anemia may also be linked to celiac disease, homocystinuria, cobalt deficiency, childhood malnutrition, treatment with para-aminosalicylic acid, and poor nutrition during pregnancy, which may cause a baby to be born with pernicious anemia.
Treatment options
Treatment for pernicious anemia typically involves vitamin B12 replacement, either with injections (about 50 to 1000 mcg) or oral tablets (about 1000 mcg), as advised by a healthcare provider.
Vitamin B12 shots or supplements are recognized by the National Heart, Lung, and Blood Institute as effective for vitamin B12–deficiency anemia, supporting their use in pernicious anemia; folic acid may also be added to help prevent neurologic complications.
Therapy is usually given for about 1 month and is often enough to correct anemia and relieve symptoms, but some people need lifelong vitamin B12 supplementation. It is also important to consult a registered dietitian, as foods like red meat, eggs, and cheese are often recommended.