Should I perform an EGD and start IM vitamin B12 in a patient with low vitamin B12 levels and negative IFA and PCA tests?

Management of Low Vitamin B12 with Negative IFA and PCA Tests

Yes, you should perform an EGD and start IM vitamin B12 in a patient with low vitamin B12 levels and negative IFA and PCA tests, as negative antibody tests do not rule out atrophic gastritis requiring parenteral B12 therapy.

Diagnostic Considerations

Understanding Negative IFA and PCA Tests

• Negative intrinsic factor antibody (IFA) and parietal cell antibody (PCA) tests do not exclude atrophic gastritis, as seronegative cases have been documented 1
• Studies have shown no significant difference in hematological, biochemical, and histological parameters between IFA-positive and IFA-negative gastritis patients 2
• These may represent different points in the spectrum of the same disease process, potentially initiated by H. pylori 2

Indications for EGD

• EGD with biopsies is recommended in patients with vitamin B12 deficiency without a clear cause to evaluate for atrophic gastritis 3
• Topographical biopsies should be obtained to determine anatomic extent and histologic severity for risk stratification 4
• In patients with newly diagnosed pernicious anemia, upper endoscopy should be considered for risk stratification and to evaluate for prevalent gastric neoplasia and neuroendocrine tumors (NETs) 4

Treatment Approach

Vitamin B12 Replacement

• Intramuscular vitamin B12 administration should be considered in patients with severe deficiency or neurologic manifestations 3, 5
• Patients with pernicious anemia require monthly injections of vitamin B12 for the remainder of their lives 6
• Failure to maintain treatment will result in return of anemia and development of incapacitating and irreversible damage to the nerves of the spinal cord 6

Monitoring Treatment

• During initial treatment of patients with pernicious anemia, serum potassium must be closely observed for the first 48 hours and replaced if necessary 6
• Hematocrit and reticulocyte counts should be repeated daily from the fifth to seventh days of therapy and then frequently until the hematocrit is normal 6
• If reticulocytes have not increased after treatment or if reticulocyte counts do not continue at least twice normal as long as the hematocrit is less than 35%, diagnosis or treatment should be reevaluated 6

Long-term Considerations

Cancer Risk and Surveillance

• Patients with pernicious anemia have about 3 times the incidence of carcinoma of the stomach as the general population 6
• Surveillance endoscopy should be considered in patients with:
  • Advanced atrophic gastritis: every 3 years 4
  • Autoimmune gastritis: interval based on individualized assessment 4

Complications of Untreated B12 Deficiency

• Vitamin B12 deficiency that progresses for longer than 3 months may produce permanent degenerative lesions of the spinal cord 6
• Neurologic manifestations will not be prevented with folic acid, and if not treated with vitamin B12, irreversible damage will result 6
• Hemolytic anemia can occur as a rare manifestation of vitamin B12 deficiency, which may mimic thrombotic microangiopathy 1

Clinical Pearls and Pitfalls

• Doses of folic acid greater than 0.1 mg per day may result in hematologic remission in patients with vitamin B12 deficiency but will not prevent neurologic manifestations 6
• Patients should be warned about the danger of taking folic acid in place of vitamin B12, as it may prevent anemia but allow progression of subacute combined degeneration 6
• Certain medications (colchicine, H2 receptor antagonists, metformin, phenobarbital, pregabalin, primidone) can contribute to vitamin B12 deficiency and should be evaluated as potential causes 4