Autoimmune Gastritis

A chronic, immune-mediated gastritis in which CD4 T cells attack the gastric parietal cells and their H+/K+ ATPase and intrinsic factor, causing corpus and fundus atrophy with sparing of the antrum.

• Prevalence is about 0.5 to 2% of the general population (higher with age, in women, and with other autoimmune disease); pernicious anaemia is the end stage of vitamin B12 deficiency.
• Associations: type 1 diabetes, autoimmune thyroid disease (Hashimoto thyroiditis, Graves disease), Addison disease, vitiligo, coeliac disease, myasthenia gravis, and primary biliary cholangitis; about 20 to 40% of patients with autoimmune thyroid disease have the antibodies.
• Mechanism: loss of parietal cells leads to achlorhydria, reduced intrinsic factor and B12 absorption, reduced iron absorption, hypergastrinaemia from antral G cell stimulation, and enterochromaffin-like cell hyperplasia that may produce type 1 gastric neuroendocrine tumours.
• Risk: gastric adenocarcinoma about 3 times higher than the general population, and type 1 neuroendocrine tumours in about 5 to 10% of patients.

Often silent for years; the first sign is iron deficiency anaemia (early disease), then vitamin B12 deficiency (late): fatigue, pallor, mild jaundice, glossitis, weight loss, anorexia.

• Neurological: paraesthesia, numbness, loss of vibration and position sense, ataxia, subacute combined degeneration of the cord, cognitive impairment, depression, optic neuropathy.
• Gastrointestinal symptoms are mild: dyspepsia, early satiety, bloating; reflux is uncommon because of achlorhydria.
• Associated autoimmune disease features: thyroid dysfunction, polyuria in diabetes, pigmentation in Addison disease.
• Differential diagnosis: H. pylori atrophic gastritis, dietary B12 deficiency (vegans), small bowel bacterial overgrowth, ileal disease (Crohn disease), metformin or proton pump inhibitor related B12 deficiency, coeliac disease, myelodysplasia, nitrous oxide misuse, other causes of macrocytosis.
• Complications: megaloblastic anaemia, pernicious anaemia, irreversible neurological damage if untreated, iron deficiency, osteoporosis, type 1 gastric neuroendocrine tumours, gastric adenocarcinoma, hypergastrinaemia, and thromboembolic risk from raised homocysteine.

Full blood count and film: macrocytosis (mean cell volume more than 100 fL), hypersegmented neutrophils, anaemia, pancytopenia; reticulocytes, lactate dehydrogenase (raised) and bilirubin (raised) show haemolysis from ineffective erythropoiesis.

• Vitamin B12 (less than 200 pg/mL or 148 pmol/L is low; 200 to 300 pg/mL is borderline: check methylmalonic acid, raised above 0.4 micromol/L, or homocysteine), folate, ferritin and iron profile.
• Antibodies: anti-parietal cell antibodies (about 80 to 90% sensitive, less specific), anti-intrinsic factor antibodies (about 50 to 60% sensitive, more than 95% specific; a positive test confirms pernicious anaemia).
• Serum gastrin (raised, often 3 to 10 times normal, in the fasting state off proton pump inhibitors), pepsinogen I (low, less than 25 micrograms/L) and a pepsinogen I to II ratio less than 3, chromogranin A (raised).
• Upper endoscopy with biopsies (five gastric biopsies: two antrum, one incisura, two corpus): corpus atrophy, intestinal and pseudopyloric metaplasia, enterochromaffin-like cell hyperplasia, antral sparing; test for H. pylori; sample any polyp or nodule.
• Screening for other autoimmune disease: thyroid stimulating hormone, glucose or HbA1c, morning cortisol if symptomatic, tissue transglutaminase IgA with total IgA.

Vitamin B12 replacement for life:

• Hydroxocobalamin 1 mg IM on alternate days for 2 weeks (until there is no further improvement when neurological symptoms are present), then 1 mg IM every 2 to 3 months.
• Cyanocobalamin alternative: 1000 micrograms IM daily for 7 days, weekly for 4 weeks, then monthly.
• High-dose oral cyanocobalamin 1000 to 2000 micrograms daily is an option for patients who cannot have injections (about 1% is absorbed by passive diffusion), with B12 level checks.
• During treatment of severe megaloblastic anaemia, check potassium at 24 and 48 hours (hypokalaemia can occur) and give potassium if low.

```{=html} <!-- --> ``` - Iron: ferrous sulfate 200 mg once daily or on alternate days (absorption is reduced by achlorhydria; take with vitamin C 500 mg), or intravenous ferric carboxymaltose 1000 mg once (maximum 20 mg/kg) when oral iron fails or is not tolerated.

• Folic acid 5 mg daily only after B12 is started (folate alone can worsen neurological disease).
• Type 1 gastric neuroendocrine tumour:
  • Tumours less than 10 mm: endoscopic surveillance every 12 months with biopsies.
  • Tumours of 10 mm or more, or multiple and rising in size: endoscopic resection (endoscopic mucosal resection or submucosal dissection), and in recurrent or refractory disease antrectomy or somatostatin analogue (octreotide long-acting release 20 mg IM every 4 weeks or lanreotide 120 mg SC every 4 to 8 weeks; evidence limited).
  • Grade 3 or invasive tumours need oncology care.
• Gastric adenocarcinoma surveillance: endoscopy with biopsies every 3 years (every 1 to 2 years with family history of gastric cancer, extensive intestinal metaplasia or dysplasia); dysplasia treated endoscopically.
• Treat associated disease: levothyroxine 1.6 micrograms/kg/day (start 25 to 50 micrograms in older adults) for hypothyroidism, insulin for diabetes, hydrocortisone and fludrocortisone for adrenal insufficiency.
• Bone health: calcium 1000 mg and vitamin D 800 to 2000 units daily, bone density scan every 2 years in older adults.
• Helicobacter pylori eradication when found: omeprazole 20 mg twice daily, amoxicillin 1 g twice daily and clarithromycin 500 mg twice daily for 14 days, or bismuth quadruple therapy (omeprazole 20 mg twice daily, bismuth subsalicylate 524 mg four times daily, tetracycline 500 mg four times daily and metronidazole 500 mg three to four times daily for 14 days).
• Special groups: children and adolescents (juvenile pernicious anaemia, genetic testing, B12 by injection, growth and thyroid checks); pregnancy (continue B12 injections, check B12 and folate, avoid bismuth and tetracycline); elderly (neurological and cognitive review, falls risk); renal impairment (continue ferrous sulfate 200 mg once daily and hydroxocobalamin 1 mg IM every 2 to 3 months; no proton pump inhibitor dose change is needed); vegans and metformin users (annual B12 checks).
• Red flags: neurological signs, pancytopenia, weight loss, dysphagia, new anaemia on treatment, gastric nodules or polyps, rising chromogranin A.
• Follow-up: B12 and full blood count at 2 to 4 weeks, 3 months and then every 6 to 12 months; ferritin at 3 months; thyroid function and glucose yearly; endoscopy with biopsies every 3 years (every 1 to 2 years with family history, extensive metaplasia or dysplasia); lifelong B12 replacement.