What is the next step in management for a patient with low vitamin B12 levels and negative Intrinsic Factor Antibody (IFA) and Parietal Cell Antibody (PCA) tests?

Upper Endoscopy (EGD) is Recommended for Low B12 with Negative IFA and PCA

For patients with low vitamin B12 levels and negative Intrinsic Factor Antibody (IFA) and Parietal Cell Antibody (PCA) tests, an upper endoscopy (EGD) with gastric biopsies is recommended as the next step in management to evaluate for atrophic gastritis.

Rationale for EGD in B12 Deficiency

• Vitamin B12 deficiency with negative antibodies may still indicate atrophic gastritis, which requires histological confirmation through endoscopy 1
• Corpus-predominant atrophic gastritis can cause vitamin B12 deficiency due to reduced intrinsic factor and gastric acid secretion, even in seronegative cases 1
• Seronegative autoimmune gastritis has been reported in patients with vitamin B12 deficiency, making histological evaluation necessary 2

Diagnostic Approach for B12 Deficiency

• Atrophic gastritis is a common cause of B12 deficiency and requires histopathologic confirmation through gastric biopsies 1
• When performing EGD, follow the updated Sydney protocol for obtaining topographical biopsies (5 biopsies from antrum, corpus, and incisura angularis) to properly assess the extent and severity of atrophic gastritis 1
• At minimum, biopsies should be placed in 2 separate specimen jars labeled antrum/incisura and body 1

Importance of Histological Diagnosis

• Despite negative antibody tests, histological examination can reveal corpus-predominant atrophic gastritis with loss of parietal cells, explaining B12 malabsorption 1
• Studies show that some patients with severe B12 deficiency may have atrophic gastritis despite negative antibody tests 2, 3
• The diagnosis of atrophic gastritis requires histopathological confirmation regardless of serological findings 1

Additional Testing Considerations

• During endoscopy, test for H. pylori infection, as it can contribute to atrophic gastritis and B12 deficiency 1
• Consider repeating antibody testing, as some studies show variable sensitivity of PCA (68.2%) and IFA (40.9%) tests 4
• Evaluate for iron deficiency alongside B12 deficiency, as both can occur in atrophic gastritis 1

Management Following Diagnosis

• If atrophic gastritis is confirmed, parenteral vitamin B12 replacement is recommended, particularly if intrinsic factor deficiency is suspected 5
• For pernicious anemia, the recommended treatment is 100 mcg of vitamin B12 daily for 6-7 days by intramuscular injection, followed by maintenance therapy 5
• Consider surveillance endoscopy every 3 years for patients diagnosed with advanced atrophic gastritis due to increased risk of gastric cancer and neuroendocrine tumors 1

Common Pitfalls to Avoid

• Do not rely solely on negative antibody tests to rule out atrophic gastritis, as seronegative cases occur in up to 40% of patients with histologically confirmed disease 3, 6
• Avoid treating with oral B12 alone without determining the cause, as malabsorption may prevent adequate replacement 5
• Do not overlook the potential for gastric neoplasia in patients with atrophic gastritis, which requires endoscopic surveillance 1