Pernicious anemia is the end stage of an autoimmune disorder in which parietal cell autoantibodies against H⁺K⁺-adenosine triphosphatase cause loss of gastric parietal cells. The loss of parietal cells reduces and then completely prevents production of intrinsic factor. In addition, blocking autoantibodies can bind to the B₁₂ binding site for intrinsic factor and prevent the formation of the B₁₂-intrinsic factor complex. Deficiency of intrinsic factor gradually results in B₁₂ deficiency (see “Clinical Effects of Inadequate Intake”).

The prevalence of undiagnosed, untreated pernicious anemia was recently estimated to be approximately 2 percent in a nonrandom sample of free-living elderly aged 60 years or older in Southern California (Carmel, 1996). Rates were higher for white and black women than for Latin American or Asian women and for all men. These estimates are consistent with the 2.9 percent prevalence of intrinsic factor antibody in individuals older than 60 years (Krasinski et al., 1986). Earlier studies reported a higher prevalence of anti-intrinsic factor antibody in blacks with pernicious anemia than in whites with pernicious anemia (Carmel, 1992) and an earlier onset of pernicious anemia in blacks (Carmel et al., 1987; Houston et al., 1985) and Hispanics (Carmel et al., 1987). Approximately 20 percent of relatives of patients with pernicious anemia also have pernicious anemia (Toh et al., 1997). Pernicious anemia carries an excess risk of gastric carcinoma (1 to 3 percent) and of gastric carcinoid tumors (Hsing et al., 1993).