Ménétrier's Disease

Synonyms: Menetriere's Disease, Ménétrier's Disease, giant hypertrophic gastritis, protein losing gasteropathy, protein losing enteropathy, hypertrophic gastropathy.

This much-misspelled disease was named for Pierre Eugene Ménétrier, a French physician (1859-1935) who first described it in 1888.¹

It is a rare condition characterised by gross hypertrophy of the gastric mucosa, resulting in an increased production of mucus, reduced acid secretion, and - due to selective serum protein loss across the gastric mucosa - severe hypoproteinaemia.² A similar hypertrophic gastritis has been recognised with Helicobacter pylori infection and in children associated with cytomegalovirus infection (a self limiting condition).^3,4,5 Recent work suggests that helicobacter isolated from patients with Menetrier's is genetically different from that isolated from patients with other gastric diseases.

Recent research implicates overproduction of transforming growth factor-alpha with increased signalling of the epidermal growth factor receptor (EGFR) in the pathogenesis of the condition. Activation of the EGFR, a transmembrane receptor with tyrosine kinase activity, triggers a cascade of downstream, intracellular signalling pathways that leads to expansion of the proliferative compartment within the isthmus of the gastric mucosa (oxyntic) cells. The result is that gastric mucus production is increased and gastric acid production is decreased.⁵ The existence of the disease in twins suggest that at least some cases have a genetic cause.⁶

Symptoms include nausea, epigastric pain, weight loss and diarrhoea ±melaena.⁷ The severe hypoproteinaemia can result in ascites and gross oedema.

The condition needs to be differentiated from other forms of hypertrophic gastropathy such as Zollinger Ellison syndrome, hypertrophic hypersecretory gastropathy, lymphocytic gastritis, or gastric carcinoma.⁷

• The diagnosis of choice is gastroscopy with gastric mucosal biopsy.Characteristic histologic changes include foveolar hyperplasia, cystic dilation of pits, and reduced numbers of parietal and chief cells.⁵ (Foveolar cells are mucus cells that cover the gastric mucosal surface and line the gastric pits. For a diagram of gastric mucosal cells, check this reference.⁸)
• Transabdominal ultrasound can provide additional information which helps to differentiate patients with giant gastric folds associated with malignancy from those with benign conditions.⁹

• There is evidence that Menetrier's is linked to cytomegalovirus in children and Helicobacter in adults, and if either of these infections is present they should be eradicated.^4,5
• Chronic disease is sometimes improved with H2 antagonists or proton pump inhibitors.^10,11
• Octreotide, a somatostatin analogue, has been used to good effect in some patients and may obviate the need for surgery.¹²
• Erbitux, a monoclonal antibody that blocks ligand binding to epidermal growth factor receptor, has shown promising results in some patients.¹³
• Therapies targeting increased signalling of the EGFR have shown promise, including somatostatin analogues and monoclonal antibodies (eg, cetuximab) directed against the EGFR.⁵
• Partial gastrectomy is occasionally recommended for persistent symptoms and particularly for uncontrollable protein loss.¹⁴ A total laparoscopic gastrectomy has also been reported.¹⁵

There is a well documented link between Menetrier's Disease and gastric carcinoma.¹⁶