History and exam

Other diagnostic factors

common

age >60 years

Up to 25% of patients over the age of 60 years are achlorhydric and >2% have pernicious anemia.[20][21][22][23][24][30][31][35][36][37][38]

female sex

Pernicious anemia is twice as common in females. Gastric carcinoids due to chronic atrophic gastritis are 3 times more common in females.[66]

autoimmune disorders

Autoimmune disorders that are more common in patients with autoimmune gastritis include Graves disease, myxedema, autoimmune thyroiditis, postpartum thyroiditis, type 1 diabetes mellitus, idiopathic adrenal insufficiency, vitiligo, hypoparathyroidism, and primary biliary cholangitis.[52][53][54][55][56][57]

weakness

Symptomatic anemia due to cobalamin (vitamin B12) and/or iron deficiency.

lethargy

Symptomatic anemia due to cobalamin (vitamin B12) and/or iron deficiency.

decreased exercise tolerance

Symptomatic anemia due to cobalamin (vitamin B12) and/or iron deficiency.

skin and conjunctival pallor

Manifestation of anemia.

paresthesias and difficulty ambulating

Neurologic manifestations of cobalamin deficiency.[101][102]

uncommon

nutritional deficiency (cobalamin, iron, calcium, vitamin D)

Atrophic gastritis is accompanied by an absence of intrinsic factor, which is normally present in parietal cells and necessary for cobalamin (vitamin B12) absorption in the terminal ileum.[15][78] Acid facilitates the absorption of iron and possibly calcium, and prevents bacterial overgrowth. The latter may induce a mild fat malabsorption with impaired uptake of fat-soluble vitamins such as vitamin D.[103]

enteric infection

Gastric acid protects against enteric infection, and achlorhydric patients have been reported to be more prone to infection with Clostridium difficile, Salmonella, Campylobacter, and possibly spontaneous bacterial peritonitis.[104][105][106]

memory loss, irritability, depression, and dementia

Manifestations of cobalamin deficiency.[78][101][107]

ataxia, shuffling gait, decreased position sense, decreased vibration sense

Manifestations of subacute combined degeneration of dorsal and lateral spinal columns from cobalamin deficiency.[78][101][102]

pale, smooth, and glossy tongue

Manifestation of cobalamin deficiency.[108]

koilonychia

Spoon nails, a manifestation of iron-deficiency anemia.[109]

Risk factors

strong

autoimmune disorders

The strongest association is with pernicious anemia and autoimmune gastritis. Other autoimmune disorders that are more common in patients with autoimmune gastritis include thyroid disease, idiopathic adrenocortical insufficiency, vitiligo, type 1 diabetes mellitus, hypoparathyroidism, and primary biliary cholangitis.[52][53][54][55][56][57]

age >60 years

Although the prevalence of atrophic gastritis and autoimmune gastritis increases with age, about one half of pernicious anemia patients are less than 60 years old and 10% are between 30 and 40 years old.[59] Up to 25% of older people may develop achlorhydria.[20][21][22][23][24][60]

Helicobacter pylori infection

Chronic infection with H pylori predisposes to atrophic gastritis and autoimmune gastritis; it may be the most common underlying cause of these disorders. However, once achlorhydria develops, most patients no longer harbor the organism.[1][36][37][38][61][62][63][64]

prior gastric surgery

Antrectomy removes the G cells and thus eliminates the trophic and secretory effects of gastrin on the oxyntic mucosa. Bile reflux may contribute to gastric atrophy. Vagotomy removes the effect of centrally acting stimulants of acid secretion such as the thought, sight, smell, and taste of food.[1]

hypergastrinemia

The most common cause of marked hypergastrinemia is atrophic gastritis with associated achlorhydria. This is a physiologic response to decreased production of acid, and serum gastrin concentrations are frequently as high as 1000 picograms/mL or more (i.e., in the range observed in patients with gastrinoma [Zollinger-Ellison syndrome]).[1]

gastric carcinoid

Between 70% and 80% of gastric carcinoid tumors arise in patients with atrophic gastritis, particularly in those with pernicious anemia.

In 71 patients with pernicious anemia followed for 6 years, 8 gastric carcinoids (11.2%) were found; all but one were removed endoscopically, and no metastasis occurred.[65] It is thought that enterochromaffin-like cells, under stimulation of gastrin, evolve through hyperplasia, dysplasia, and eventually neoplasia. These carcinoid tumors are typically small, polypoid, multicentric, and well differentiated.[66]

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