MéNéTrier Disease

Ménétrier disease is a rare acquired hypertrophic gastropathy with giant gastric folds, foveolar hyperplasia, hypochlorhydria and protein losing gastropathy.

• Incidence 0.2 per million; men more than women; adults aged 30 to 60; children (transient, associated with cytomegalovirus).
• Pathogenesis: overexpression of transforming growth factor alpha with excessive epidermal growth factor receptor activation in surface mucous cells, causing foveolar hyperplasia and loss of parietal cells.
• Infectious associations: Helicobacter pylori (in adults, some cases), cytomegalovirus (children).
• Premalignant: increased risk of gastric adenocarcinoma (2 to 15%).
• Complications: hypoalbuminaemia, oedema, anaemia, weight loss, thromboembolism, gastrointestinal bleeding.

• Epigastric pain, nausea, vomiting, anorexia, weight loss, early satiety.
• Peripheral oedema, ascites, pleural effusions from protein loss.
• Diarrhoea, bleeding (occult), anaemia.
• Differential diagnosis: Zollinger-Ellison syndrome, lymphoma, gastric carcinoma (linitis plastica), hypertrophic lymphocytic gastritis, infiltrative disease, juvenile polyposis, amyloidosis, sarcoidosis, eosinophilic gastritis.

• Upper endoscopy: massively enlarged, tortuous, cerebriform rugal folds in the gastric fundus and body with antral sparing; folds do not flatten with insufflation.
• Deep mucosal biopsies (bite on bite, snare or endoscopic mucosal resection) showing foveolar hyperplasia, cystic dilatation of glands, reduced parietal and chief cells, mucus cell predominance, and normal or inflammatory lamina propria.
• Gastric pH over 5 (hypochlorhydria), elevated gastrin may be normal.
• Protein loss: low albumin, faecal alpha 1 antitrypsin clearance.
• Exclude other causes: serum gastrin, H. pylori testing (histology, stool antigen), CMV testing (PCR, immunohistochemistry), CT abdomen, endoscopic ultrasound (mucosal thickening, intact muscularis), lymphoma markers.

• Eradicate Helicobacter pylori if present (omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily for 14 days, or bismuth quadruple therapy), which can induce remission.
• Cetuximab (anti EGFR monoclonal antibody) 500 mg/m2 IV every 2 weeks for 4 doses (or weekly 400 mg/m2 initial then 250 mg/m2): remission in over 90% of cases with improvement in protein loss and histology; monitor for rash, hypomagnesaemia, infusion reactions.
• Supportive: high protein diet, albumin infusion for severe hypoalbuminaemia, diuretics for oedema, iron and vitamin replacement.
• Acid suppression (PPI) has little benefit unless symptomatic peptic disease; octreotide 100 to 200 micrograms SC three times daily or long acting 20 mg monthly can reduce protein loss; prednisolone 20 to 40 mg short course; anticholinergics, prostaglandin analogues, H2 blockers (limited).
• Pediatric disease (CMV): supportive care, ganciclovir 5 mg/kg IV twice daily for severe cases; spontaneous remission in weeks.
• Total or subtotal gastrectomy for refractory hypoalbuminaemia, severe symptoms, bleeding, or dysplasia/carcinoma.
• Endoscopic surveillance every 1 to 2 years with biopsies for dysplasia and adenocarcinoma.
• Thromboprophylaxis in severe protein loss and immobility.