PERNICIOUS ANAEMIA - a patient's guide
What is it?
Pernicious Anaemia (PA) is one of the causes of vitamin B12 deficiency. It is an autoimmune condition where the patient makes antibodies against intrinsic factor (IF) - the latter is essential for vitamin B12 to be absorbed from food.
IF is produced by special cells in the stomach wall - in people with PA, the lining of the stomach becomes thin, acid secretion is decreased and IF production is almost absent. Also, there is an increased incidence of cancer of the stomach in people with PA (occurs in about 2-3% of all cases).
Anaemia is defined as a reduced haemoglobin level in the blood (the pigment in red cells that carry oxygen around the body). As the B12 level falls, an individual becomes progressively anaemic and pale, dizzy and short of breath.
Severe vitamin B12 deficiency can also cause progressive damage to the nerves, particularly those involved in sensation, as well as the spinal cord. A patient affected will often note tingling in the feet with difficulty in walking and problems with balance.
Occasionally, damage to the optic nerves or severe psychiatric symptoms can be present. This nerve damage can occur even when the anaemia is only mild or even absent, although there are always other abnormalities seen on the blood film and in the bone marrow. The exact cause of the neuropathy in this condition is still not completely explained.
Why people develop pernicious anaemia is unknown, but there appears to be a genetic basis. The incidence increases with age with the peak at 60 years of age - slightly more women develop this condition in comparison to men (1.6:1).
PA, although most common in people of northern European origin, is said to be found in all races, and tends to occur more commonly in families with an affected person. It is also associated with early greying of the hair and with the blood group A.
Other autoimmune conditions tend to occur more commonly in the patient or the extended family compared to the general population. These include thyroid diseases, failure of the adrenal gland, vitiligo (a skin rash which causes patches of depigmentation), failure of parathyroid glands and a reduced ability to make antibodies, (hypogammaglobulinaemia).
When PA is advanced, patients have a "megaloblastic anaemia" with less haemoglobin and red cells, and each red cell is much larger than normal (macrocytes). Other blood cells may also be mildly reduced, especially in those with severe anaemia.
Bone marrow tests are performed if there is uncertainty about the diagnosis. The red cells often have a reduced life span and their increased destruction can lead to a yellow colour of the skin and the whites of the eyes (jaundice).
To make the diagnosis, blood tests need to show a low serum B12 level. In some patients vitamin B12 deficiency can coexist with folate deficiency, which can cause the same blood changes but not the nerve damage - thus which deficiency is the true cause of any anaemia can be difficult to sort out. In those instances additional special tests may be necessary, and/or the response to treatment with low dosages of one or the other vitamin can be used as a treatment trial.
Large doses of folic acid in B12 deficiency can improve the anaemia, but may aggravate the nerve damage, thus folate should not be given alone unless B12 deficiency has definitely been excluded.
The diagnostic test for pernicious anaemia is the identification of IF antibodies in the blood - these however occur in only about half of the patients.
If IF antibodies are not present, a Schilling test is often performed, which uses oral doses of radioactive labelled vitamin B12 with and without an active IF preparation. This allows stomach problems to be distinguished from intestinal causes (IF corrects the absorption of B12 in PA and other stomach lesions, but not in intestinal diseases).
In cases of PA, gastroscopy should be done to exclude cancer of the stomach, especially those with pain, bleeding from the bowel and unexplained weight loss after treatment.
There is a childhood form of PA, which can be due to the production of an abnormal intrinsic factor. In the latter there is usually a normal stomach and normal acid secretion - although occasionally the adult form of PA can occur in childhood.
Congenital lack of IF usually presents about two years of age when the stores of vitamin B12 that are transferred from the mother in utero, have all been used.
Other causes of vitamin B12 deficiency, other than Pernicious Anaemia:
In western countries, vitamin B12 deficiency is usually due to PA. Less commonly, the deficiency may occur after gastric surgery when a considerable amount of the stomach has been removed, or in small bowel diseases, or surgical removal of the part of the bowel where the vitamin is absorbed (ileum).
Vitamin B12 deficiency is also caused by veganism when the diet lacks sufficient B12 (more common in Hindu Indians), as the vitamin is only present in foods of animal origin (meat, eggs, milk). Once B12 absorption or IF production is absent, the deficiency takes at least two years to develop. This is the time it takes for the body stores (mainly in the liver) to become depleted after absorption ceases.
Rarer small bowel causes of vitamin B12 deficiency include chronic tropical sprue, Crohn's disease and infection with fish tapeworms in some parts of the world.
Treatment of PA involves vitamin B12 given by injection. (There is a nasal preparation coming on the market in some countries).
In the early stage of treatment, careful attention to blood potassium levels is necessary in severe cases, as the B12 pushes potassium into the blood cells, making the blood level very low. The patient feels better after 24 - 48 hours of therapy with increased appetite and well being.
A response to treatment can be seen in the laboratory as early as the second or third day with young red cells peaking in the blood at six to seven days. The haemoglobin level continues to rise by 20 - 30 grams each fortnight and other blood changes gradually disappear over the next twelve days.
The peripheral neuropathy may partly improve with therapy, but any spinal cord damage is irreversible. Treatment for pernicious anaemia is lifelong.
Who should be tested for Pernicious Anaemia?
All patients with megaloblastic or macrocytic anaemia should have B12 levels done.
Anyone presenting with peripheral neuropathy and evidence of spinal cord damage, and neuropsychiatric disorders including dementia should have B12 levels performed.
Patients who are malnourished or infertile should be tested.
Those patients who have had a total gastrectomy, or removal of part of the small bowel which absorbs B12 should have regular monitoring of their levels and may need to start receiving vitamin B12 injections when their levels fall a year or two after surgery.
Individuals with a strong family history should have levels tested infrequently, or earlier if clinically indicated.