- Pernicious anemia is a form of megaloblastic anemia caused by vitamin B12 (cobalamin) deficiency, specifically resulting from the inability to absorb vitamin B12 in the gastrointestinal tract. This condition arises due to a lack of intrinsic factor, a protein secreted by the parietal cells of the stomach that is essential for vitamin B12 absorption in the small intestine.
- Without intrinsic factor, vitamin B12 cannot be efficiently absorbed, leading to progressively worsening deficiency. Pernicious anemia is classified as an autoimmune disorder, where the body produces antibodies that attack either intrinsic factor itself or the gastric parietal cells that produce it.
- Vitamin B12 plays a crucial role in DNA synthesis, red blood cell formation, and neurological function. In pernicious anemia, the impaired absorption of B12 results in the production of abnormally large and immature red blood cells (megaloblasts) in the bone marrow, which are inefficient at transporting oxygen. Additionally, B12 deficiency can lead to neurological symptoms, as it is involved in the maintenance of the myelin sheath that protects nerve cells.
- Symptoms of pernicious anemia typically develop gradually and may go unrecognized in early stages. Common signs include fatigue, pallor, shortness of breath, weakness, and dizziness, due to reduced oxygen-carrying capacity of the blood. As the condition progresses, neurological symptoms such as numbness and tingling in the hands and feet, balance difficulties, memory loss, depression, and cognitive decline may appear. In advanced cases, these neurological effects can become irreversible if left untreated. Glossitis (a swollen, inflamed tongue) and gastrointestinal disturbances, such as nausea or appetite loss, are also frequent findings.
- Diagnosis is based on clinical history, symptoms, and laboratory findings. Blood tests typically reveal macrocytic anemia (enlarged red blood cells with high mean corpuscular volume), low serum B12 levels, and elevated levels of methylmalonic acid (MMA) and homocysteine—metabolites that accumulate in B12 deficiency. The presence of anti-intrinsic factor antibodies or anti-parietal cell antibodies in the blood supports the diagnosis of pernicious anemia. Bone marrow biopsy is rarely needed but may show megaloblastic changes if performed.
- Treatment for pernicious anemia involves lifelong vitamin B12 replacement, typically through intramuscular injections of cyanocobalamin or hydroxocobalamin, especially in cases where oral absorption is impaired. High-dose oral B12 supplementation may be effective in some patients through passive diffusion, even without intrinsic factor, but parenteral therapy is preferred for those with severe deficiency or neurological symptoms. Once therapy begins, symptoms usually improve over weeks to months, though long-standing nerve damage may be only partially reversible.
- Because pernicious anemia is associated with autoimmune gastritis, patients are at increased risk for other autoimmune conditions, such as type 1 diabetes, Hashimoto’s thyroiditis, and vitiligo, as well as gastric carcinoma. Therefore, ongoing monitoring and regular follow-up are important. Early detection and appropriate treatment are essential to prevent permanent neurological damage and restore normal hematologic function.
