pernicious anemia

Pernicious anemia (PA) is the commonest cause of vitamin B12 deficiency (or hypocobalaminemia) in the world, due to an autoantibody against intrinsic factor, the cofactor required for absorption of this vitamin.

Epidemiology

Pernicious anemia is the commonest cause of hypovitaminosis B12 globally. Its prevalence in the US has been determined as ~150/100,000.

Associations

Pernicious anemia patients have an increased risk of developing other autoimmune conditions :

Clinical presentation

Typically the patient presents non-specifically with a gradual lethargy and deteriorating mentation, which correlate to worsening anemia.

Demyelination is a sequela of the hypocobalaminemia leading to subacute combined degeneration of the cord (SACD). This manifests clinically initially as dysfunction of vibration sense and persistent 'pins-and-needles'. As the condition advances more overt posterior column dysfunction is seen. Autonomic neuropathy and dementia present later, with an approximate 1-2% prevalence in established disease. Myelopathy, seen as loss of motor function, is also seen, in ~12% cases.

Occasionally the neurological deficits present without evidence of anemia.

Due to the association with other autoimmune conditions, patients may also present with features of related diseases, e.g. thyroid dysfunction.

Diagnosis

Historically the Schilling test was employed, however this is no longer available.

Diagnostic confirmation now relies upon testing for the presence of autoantibodies against intrinsic factor.

Pathology

The body's absorption of cobalamin is reliant on two proteins:

  • salivary haptocorrin, which binds the cobalamin in the mouth, and then passes to the stomach, where the acidity and pepsin-mediated proteolysis releases most of the cobalamin from its complex with haptocorrin
  • parietal cells of the gastric mucosa secrete intrinsic factor, a glycoprotein, which attaches to the cobalamin molecule, and the combined moiety passes to the ileum where it is absorbed 
  • Pernicious anemia is an autoimmune disease in which the body forms antibodies against the intrinsic factor itself, and also against the gastric parietal cells. Consequentially, the absorption of cobalamin is impaired.

    Virtually all patients with pernicious anemia develop chronic atrophic gastritis (CAG). This seems to be due to autoantibodies formed against the ATPase of the proton pumps of the parietal cells.

    Radiographic features

    Generally imaging of pernicious anemia per se is unremarkable.

    The imaging features of subacute combined degeneration of the cord are described in a separate article.

    Pernicious anemia increases risk of gastric adenocarcinoma almost seven-fold, and therefore careful review of the stomach is warranted on imaging of it. However in absolute terms this equates to an annual incidence rate for development of gastric carcinoma of only 0.27% per person-years .

    Treatment and prognosis

    A true cure remains elusive. Fortunately despite the underlying pathology of malabsorption of vitamin B12, the condition remains treatable with oral vitamin intake, which is thought to be due to non-intrinsic factor-dependent absorption, as well as some remnant IF activity which is only blunted by the autoantibodies.

    History and etymology

    Thomas Addison first detailed this condition in 1849, described as a clinical presentation of pallor, asthenia and insidious and relentless deterioration of one's health. Initially it was known as Addison's anemia. Later it was given its current monicker due to its universally inexorable fatal prognosis