What is the recommended management for a 17‑year‑old male with documented vitamin B12 deficiency and a positive parietal‑cell antibody (2.9) indicating autoimmune gastritis/pernicious anemia?

Management of a 17-Year-Old Male with B12 Deficiency and Positive Parietal Cell Antibody

This patient requires lifelong vitamin B12 replacement therapy and upper endoscopy with gastric biopsies to confirm autoimmune atrophic gastritis, screen for neuroendocrine tumors, and establish a surveillance plan.

Immediate Treatment Approach

Vitamin B12 Replacement

• Initiate oral vitamin B12 at 1,000 mcg daily as first-line therapy, with recheck of B12 levels at 40 days to confirm adequate response 1
• Reserve intramuscular B12 (100 mcg daily for 6-7 days, then alternate days for seven doses, then every 3-4 days for 2-3 weeks, followed by 100 mcg monthly for life) for patients who fail to respond to oral therapy 2
• The oral route is now considered first-line despite older FDA labeling emphasizing parenteral therapy, as modern evidence supports oral efficacy in most patients 1

Concurrent Iron Assessment and Treatment

• Evaluate for iron deficiency immediately, as it occurs in up to 50% of patients with autoimmune gastritis and manifests earlier than B12 deficiency 3, 4
• Iron deficiency is a priority for screening and treatment because iron stores deplete more rapidly than B12 stores 3, 4
• If folate deficiency is present, administer folic acid 1 mg daily concomitantly 1

Diagnostic Confirmation with Upper Endoscopy

Indications for Endoscopy

• All patients with new diagnosis of pernicious anemia who have not had recent endoscopy should undergo upper endoscopy with topographical biopsies 4
• This is necessary even with positive parietal cell antibodies because: (1) histological confirmation is required for definitive diagnosis, (2) risk stratification depends on extent of atrophy, and (3) prevalent gastric neoplasia including neuroendocrine tumors must be ruled out 4, 1
• Positive parietal cell antibodies (97% sensitivity in confirmed cases) strongly suggest autoimmune gastritis, but histological confirmation remains the gold standard 5

Biopsy Protocol

• Obtain biopsies from the gastric body and antrum/incisura using the updated Sydney protocol 1
• Place biopsies in 2 separate specimen jars labeled "antrum/incisura" and "body" to properly assess extent and severity of atrophic gastritis 4, 1
• Test for H. pylori infection during endoscopy, as it can contribute to atrophic gastritis; if positive, treat and confirm eradication with non-serological testing 4, 1

Surveillance Strategy

Neuroendocrine Tumor Screening

• All individuals with confirmed autoimmune gastritis should be screened for type 1 gastric neuroendocrine tumors (GNETs) 4
• GNETs were found in 18% (6/34) of patients with pernicious anemia in one endocrinology practice series 5
• Small neuroendocrine tumors should be removed endoscopically, followed by surveillance endoscopy every 1-2 years depending on tumor burden 4

Long-Term Gastric Cancer Surveillance

• Surveillance endoscopy every 3 years is recommended for patients with advanced atrophic gastritis (defined by anatomic extent and histologic grade) 4, 1
• This surveillance is critical because autoimmune gastritis carries increased risk for both gastric adenocarcinoma and neuroendocrine tumors 4, 5

Screening for Associated Autoimmune Conditions

• Screen for autoimmune thyroid disease, as it is common in patients with autoimmune gastritis 4
• In one series, 94% (32/34) of patients with pernicious anemia had concomitant autoimmune or immunologic diseases 5
• Consider screening for other autoimmune conditions including type 1 diabetes, celiac disease, and Sjögren syndrome based on clinical suspicion 6, 5

Important Clinical Considerations

Seronegative Autoimmune Gastritis

• While this patient has positive parietal cell antibodies (2.9), be aware that seronegative autoimmune gastritis exists 7
• Intrinsic factor blocking antibody (IFBA) is only 52% sensitive, so negative IFBA does not exclude the diagnosis 5
• Histological examination can reveal corpus-predominant atrophic gastritis with parietal cell loss even when antibodies are negative 1, 7

Rare but Serious Presentations

• Severe B12 deficiency can present as pseudothrombotic microangiopathy with hemolytic anemia, schistocytes, and thrombocytopenia, mimicking TTP 7, 8
• Key distinguishing features favoring B12 deficiency over TTP include: decreased reticulocyte count and LDH >2,500 IU/L 8
• Neurologic complications including subacute combined degeneration of the spinal cord can occur and may be irreversible if treatment is delayed 5

Monitoring Response to Treatment

• Recheck B12 levels at 40 days to confirm adequate response to oral therapy 1
• Monitor hemoglobin and MCV to assess hematologic response 8, 9
• Continue lifelong B12 supplementation, as this condition requires permanent replacement therapy 2, 8