Vitamin B-12 Deficiency Anemia /Pernicious anemia (also known as Biermer’s disease) is an autoimmune atrophic gastritis, predominantly of the fundus, and is responsible for a deficiency in vitamin B12 (cobalamin) due to its malabsorption. Its prevalence is 0.1% in the general population and 1.9% in subjects over the age of 60 years. Pernicious anemia represents 20%–50% of the causes of vitamin B12 deficiency in adults. Given its polymorphism and a broad spectrum of clinical manifestations, pernicious anemia is a great pretender. Its diagnosis must, therefore, be revoked and considered in the presence of neurological and hematological manifestations of undetermined origin. Biologically, it is characterized by the presence of anti-intrinsic factor antibodies. Treatment is based on the administration of parenteral vitamin B12, although other routes of administration (eg, oral) are currently under study. In the present update, these various aspects are discussed with special emphasis on data of interest to the clinician.
Pernicious anemia is the loss of stomach cells that make intrinsic factor. Intrinsic factor helps the body absorb vitamin B12 in the intestine. The loss of parietal cells may be due to destruction by the body’s own immune system.
Pernicious anemia (PA) (also known as Biermer’s disease[Rx] and Addisonian anemia[Rx]) is a macrocytic anemia due to vitamin B12 (cobalamin) deficiency, which, in turn, is the result of deficiency of intrinsic factor, a protein that binds avidly to dietary vitamin B12 and promotes its transport to the terminal ileum for absorption[Rx]. The deficiency of intrinsic factor is a consequence of the presence of atrophic body gastritis (ABG), which results in the destruction of the oxyntic mucosa, and thus, the loss of parietal cells, which normally produce chlorhydric acid as well as an intrinsic factor[Rx]. The term PA is sometimes used as a synonym for cobalamin deficiency or for macrocytic anemia, but to avoid ambiguity, PA should be reserved for conditions that result from the impaired secretion of intrinsic factor and atrophy of oxyntic mucosa. However, differential diagnosis may sometimes be challenging due to the limit of available diagnostic tools.PA is considered an autoimmune disorder due to the frequent presence of gastric autoantibodies directed against intrinsic factor, as well as against parietal cells. PA is often considered a synonym of autoimmune gastritis because PA is thought to be the end stage of an autoimmune process that results in severe damage of the oxyntic gastric mucosa[Rx].
Causes of Vitamin B-12 Deficiency Anemia
- Autoimmune diseases, such as type 1 diabetes
- Crohn’s disease
- Having part or all of your stomach or intestine taken out
- dairy products
- fortified soy, nut, and rice milks
- nutritional supplements
- long-term use of certain medications and antibiotics, such as methotrexate and azathioprine
- chronic obstructive pulmonary disease (COPD)
- folate (vitamin B-9) deficiency caused by poor diet or conditions that affect absorption
- chronic alcoholism
- Cimetidine (used to treat peptic ulcers)
- Omeprazole and Lansoprazole (proton pump inhibitors)
- Phenobarbital, Pregabalin, Primidone and Topiramate (epilepsy)
- Metformin (Type 2 Diabetes)
- A strict vegetarian diet puts you at risk for PA too, since you won’t be eating foods that are rich in B-12 like eggs, milk, and poultry.
- Pernicious anemia is a type of macrocytic anemia. It’s sometimes called megaloblastic anemia because of the abnormally large size of the red blood cells produced.
Pathologically, PA is characterized by at least the following elements:
The destruction of the gastric mucosa, especially fundic, by a process of cell-mediated autoimmunity.Rx,
The presence of various antibodies, including antibodies detectable in both plasma and gastric secretions in the form of anti-IF antibodies and anti gastric parietal cell (anti-GPC) antibodies, the latter being specifically directed against the hydrogen-potassium adenosine triphosphatase (H+/K+-ATPase) proton pump.Rx
Certain diseases can also raise your risk. They include
- Addison disease
- Chronic thyroiditis
- Graves disease
- Myasthenia gravis
- Secondary amenorrhea
- Type 1 diabetes
- Testicular dysfunction
Symptoms of Vitamin B-12 Deficiency Anemia
PA affects people in different ways. These can be signs you have it
- Fatigue (Many people wake up tired despite getting enough sleep.)
- Shortness of breath
- Feeling dizzy
- Cold hands and feet
- Chest pain
- Pale or yellow skin
- Trouble with balance (for example, struggling to put on your pants or socks while you’re standing)
- A burning feeling in your legs or feet. This may get worse at night
- Trouble focusing
- Weight loss
- An unsteady gait
- Spasticity, which is stiffness and tightness in the muscles
- Peripheral neuropathy, which is numbness in the arms and legs
- Progressive lesions of the spinal cord
- Memory loss
- Nausea and vomiting
- Loss of appetite
Diagnosis of Vitamin B-12 Deficiency Anemia
- A complete blood cell count (CBC)
- Examination of a blood smear (peripheral smear) under a microscope, often performed in association with a CBC
- Blood vitamin B-12 level measurements
- Tests for the presence of autoantibodies to intrinsic factor or stomach lining cells
- Blood levels of iron and iron-binding capacity
- Folate levels (which are often reduced when vitamin B-12 levels are low)
- Blood levels of methylmalonic acid or homocysteine, both of which may be sensitive indicators of vitamin B-12 deficiency
- The Schilling test, a measure of how well the body can absorb vitamin B-12, is less commonly used today than in the past.
- Finally, bone marrow aspiration or bone marrow biopsy may be recommended in some cases if bone marrow disorders are suspected
- Tests to measure blood levels of methylmalonic acid (MMA) or homocysteine, both of which may be sensitive indicators of vitamin B-12 deficiency;
- An elevated MMA level is seen with B-12 deficiency, whereas elevated homocysteine levels are characteristic of both B-12 and folate deficiencies;
- Bone marrow aspiration or bone marrow biopsy may be recommended in some cases to examine for the presence of bone marrow disorders.
- Reticulocyte count, which measures how fast premature red blood cells, called reticulocytes, are made by bone marrow and released into blood
|Neuropsychiatric manifestations||Digestive manifestations||Other manifestations|
|Frequent||Frequent||Vaginal mucosa atrophy|
|Combined sclerosis of the spinal cord||Hunter’s glossitis||Urogenital infections (especially mycoses)|
|Polyneuritis||Hemolytic icterus||Rebellious or recurrent cutaneous–mucosal ulcers|
|Ataxias||Others||Thrombosis (venous thromboembolism and ischemic heart disease)|
|Babinski||Abdominal pain||Subfertility and recurrent spontaneous abortions/male infertility|
|Rare||GI transit disorders|
|Cranial nerve impairment|
Abbreviation: GI, gastrointestinal.
Treatment of Pernicious Anemia
The treatment of PA varies by country and area. Opinions vary over the efficacy of administration (parenteral/oral), the amount and time interval of the doses, or the forms of vitamin B12 (e.g. cyanocobalamin/hydroxocobalamin). More comprehensive studies are still needed in order to validate the feasibility of a particular therapeutic method for PA in clinical practices. A permanent cure for PA is lacking, although repletion of B12 should be expected to result in cessation of anemia-related symptoms, a halt in neurological deterioration, and in cases where neurological problems are not advanced, neurological recovery and a complete and permanent remission of all symptoms, so long as B12 is supplemented. Repletion of B12 can be accomplished in a variety of ways.
The standard treatment for PA has been intramuscular injections of cobalamin in the form of cyanocobalamin (CN-Cbl), hydroxocobalamin (OH-Cbl) or methylcobalamin.
Treatment with high-dose vitamin B12 by mouth also appears effective.