Pernicious anemia is a form of megaloblastic anemia that results from poor absorption of vitamin B12 rather than from an inadequate dietary supply. In this condition the stomach fails to provide sufficient intrinsic factor, a glycoprotein required for vitamin B12 uptake in the small intestine. Without intrinsic factor, dietary sources such as meat, poultry and dairy cannot be absorbed effectively, producing a progressive deficiency that affects red blood cell production and the nervous system. The general concept of anemia is discussed under anemia.

Key characteristics and symptoms

Pernicious anemia typically causes a combination of hematologic and neurologic signs. Blood abnormalities include enlarged red blood cells (macrocytosis) and a reduced number of circulating erythrocytes. Common systemic symptoms are fatigue, pallor, shortness of breath on exertion, and lightheadedness. Neurologic manifestations can include numbness and tingling in the hands and feet, unsteady gait, memory problems, and mood changes; these arise from impaired myelin maintenance and may become irreversible if treatment is delayed. Gastrointestinal complaints and a smooth, sore tongue may also occur.

Causes and risk factors

The underlying problem in pernicious anemia is an inability of the small intestine to acquire vitamin B12 because intrinsic factor is deficient or absent. Intrinsic factor is produced by acid-secreting cells in the stomach; damage to these cells or immune-mediated neutralization of intrinsic factor are common mechanisms. Autoimmune destruction of stomach (parietal) cells and antibodies that block intrinsic factor or its binding to vitamin B12 are important causes. Other contributors include chronic atrophic gastritis, prior gastric surgery, and rarely inherited predisposition. The condition is more frequent in older adults and may be associated with other autoimmune disorders affecting the thyroid or other organs.

Diagnosis

Detection relies on clinical suspicion supported by laboratory tests. Typical findings include a low serum vitamin B12 concentration, large red blood cells with increased mean corpuscular volume, and characteristic changes on a peripheral blood smear. Additional laboratory markers such as elevated methylmalonic acid and homocysteine levels indicate functional B12 deficiency. Specific testing for anti‑intrinsic factor and anti‑parietal cell antibodies helps confirm an autoimmune cause. Historically specialized tests such as the Schilling test were used to assess absorption, but modern practice favors blood markers and antibody assays.

Treatment and prognosis

Treatment replaces vitamin B12 and prevents further neurologic injury. The traditional regimen has been regular intramuscular or subcutaneous injections of vitamin B12 (injections), but high‑dose oral or intranasal formulations can be effective in many people because a small proportion of B12 is absorbed by passive diffusion. Therapy is usually lifelong for autoimmune forms of the disease. Early treatment often corrects anemia within weeks and improves neurologic symptoms, but prolonged deficiency may cause permanent neurologic damage. Monitoring includes periodic blood counts and assessment of B12 status.

Clinicians first described the clinical syndrome of pernicious anemia in the 19th century; early observers such as Thomas Addison documented its severe course before effective therapies existed. Later research identified vitamin B12 and the gastric factors required for its absorption. Because pernicious anemia is one cause among several of B12 deficiency, it is important to distinguish it from dietary insufficiency, malabsorption due to intestinal disease, or drug effects that interfere with B12 use.

  • Common dietary sources of vitamin B12 include meat and poultry as well as dairy products.
  • The stomach lining and its acid‑secreting cells are central to intrinsic factor production (stomach).
  • Autoimmune mechanisms involve the immune system attacking gastric components.
  • Because the primary problem is absorption in the intestines, replacing native gastric function is not feasible; management focuses on vitamin replacement.

For further reading and clinical guidance, consult specialist resources or clinical practice guidelines through trusted medical sources (intrinsic factor and vitamin B12 topics provide in‑depth coverage).