Megaloblastic anaemia, Addison's anaemia, Biermer's anaemia; macrocytic achylic anaemia, congenital pernicious anaemia, juvenile pernicious anaemia; vitamin B12 deficiency (malabsorption)
What is pernicious anaemia?
There are many different types of anaemia, a condition that involves red blood cell deficiencies. The result is that the blood cannot carry enough oxygen to all the cells of the body.
In pernicious anaemia, the body does not absorb enough vitamin B12 from the digestive tract, resulting in inadequate production of normal red blood cells.
Pernicious anaemia is so named because it is a serious illness that was previously incurable ("pernicious" means destructive or fatal). Nowadays it can be very effectively treated.
What causes pernicious anaemia?
Pernicious anaemia results from a lack of intrinsic factor, a protein needed to absorb vitamin B12 from the digestive tract. This causes vitamin B12 deficiency, and, as vitamin B12 is essential in the formation of red blood cells, anaemia results. Vitamin B12 deficiency also accelerates blood cell destruction and damages the nervous system.
Medical researchers think that pernicious anaemia is often caused by an autoimmune reaction (the body's defence system attacks its own tissues): the immune system destroys the cells in the stomach that secrete intrinsic factor. Many people with pernicious anaemia are found to have both chronic inflammation of the stomach lining, called atrophic gastritis, and antibodies (proteins produced by the immune system to defend against harmful invasive substances) against the intrinsic factor-secreting cells or against intrinsic factor itself.
In adults, the inability to make intrinsic factor may also be the result of chronic gastritis, or of a gastrectomy (removal of all or part of the stomach).
The condition may result from hereditary factors. Very rarely, children are born with a defect of the gene that allows for normal intrinsic factor production. Congenital (born with) pernicious anaemia is inherited as an autosomal recessive disorder (i.e. the child needs to inherit two copies of the defective gene, one from each parent, to develop the condition).
(Note: The classic definition of pernicious anaemia is that supplied above i.e. vitamin B12 deficiency and consequent anaemia caused by lack of intrinsic factor. However, there are several other causes of vitamin B12 deficiency and resultant anaemia, and the term pernicious anaemia is sometimes used to refer to these also.)
Who gets pernicious anaemia and who is at risk?
About one out of 1 000 people has pernicious anaemia. The condition can affect all racial groups, but the incidence is higher among people of Scandinavian (Northern European) descent. Slightly more women than men are affected. It is also common amongst blacks.
Other risk factors include a family history of pernicious anaemia, and a history of autoimmune endocrine disorders. (Endocrine disorders affect organs and glands that secrete hormones.) Pernicious anaemia may occur in association with autoimmune endocrine diseases such as type 1 diabetes, hypoparathyroidism, Addison's disease, hypopituitarism, testicular dysfunction, Graves disease, chronic thyroiditis, myasthenia gravis, secondary amenorrhea and vitiglio.
Although a form of the disorder can occur in children (juvenile or congenital pernicious anaemia, which usually becomes evident before the age of three years), pernicious anaemia usually does not appear before the age of 30 years. Average age at diagnosis is 60 years.
Symptoms and signs of pernicious anaemia
Many of the symptoms of pernicious anaemia are those of vitamin B12 deficiency, which for example, gradually affects sensory and motor nerves, causing neurological problems that may appear before anaemia is diagnosed. The anaemia also affects the gastrointestinal (digestive) system and the cardiovascular (blood circulation) system.
Symptoms may include:
- Fatigue and angina
- Weak muscles
- Numbness or tingling in hands and feet (paresthesias)
- Difficulty walking
- Decreased appetite
- Weight loss
- Smooth and tender or burning sensation of the tongue
- Sore mouth
- Abdominal pain
- Shortness of breath
- Slowing of mental processes
- Menstrual problems
Onset and progression of pernicious anaemia is slow, and symptoms may be subtle and often resemble several other blood conditions or medical problems, sometimes making disorder difficult to detect.
How is pernicious anaemia diagnosed?
To diagnose pernicious anaemia, your doctor will need to take a complete medical history and perform a physical examination. Diagnostic procedures for pernicious anaemia may include additional blood tests and other evaluation procedures, including the Schilling test.
The Schilling test is performed to detect vitamin B12 absorption. Vitamin B12 levels are measured in the urine after the ingestion of radioactive vitamin B12. With normal absorption, the ileum (lower part of the small intestine) absorbs more vitamin B12 than the body needs and excretes the excess through urination. With impaired absorption, little or no vitamin B12 is excreted in the urine.
How is pernicious anaemia treated?
Pernicious anaemia is treated with intramuscular vitamin B12 injections to correct the deficiency. This therapy corrects the anaemia and may correct the associated neurological complications if given early enough.
When treatment is initiated, five to seven injections may be given over a short time-span. Response to this therapy is usually seen within 48 to 72 hours.
In most centers, 1000 µg of hydroxycobalamin is given initially, by the parenteral route for seven days. However, many regimens are practised. Intramuscular injection affords vitamin repletion and induces partial or complete haematologic remission. However, life-long maintenance of vitamin supplementation together with ongoing haematologic surveillance is required. Most often, this entails need for monthly injections of vitamin B12. In exceptional and unusual cases, vitamin B12 can be given orally. Regular monitoring of the blood picture is important if this approach is to be pursued, as absorption of the vitamin supplement via the oral route is poor.
What is the outcome of pernicious anaemia?
The outcome of pernicious anaemia, if correctly treated, is usually excellent.
Complications of pernicious anaemia:
- People with pernicious anaemia may develop gastric polyps (growths of the stomach wall), and have twice the incidence of stomach cancer compared with the normal population.
- Nerve damage caused by vitamin B12 deficiency can be irreversible if treatment is delayed.
- Vitamin B12 deficiency affects the appearance of all epithelial cells (cells that form the outer skin surface and line the internal structures of the body); therefore a woman with untreated pernicious anaemia may obtain a false positive Pap smear.
Can pernicious anaemia be prevented?
Pernicious anaemia is not preventable, but with early diagnosis and treatment it can be effectively controlled.
When to call the doctor
Consult your doctor if you experience any symptoms of pernicious anaemia. Fatigue is often the first symptom of this disorder (as well as of many other conditions).
Reviewed by Prof. Don du Toit, Faculty of Health Sciences, University of Stellenbosch.