Ménétrier's disease
Ménétrier disease | |
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Other names | Hypoproteinemic hypertrophic gastropathy |
Biopsy of the stomach in Ménétrier disease showing the substantial pit hyperplasia makes the large rugal folds appear to be covered by myriad polyps resembling hyperplastic polyps. The muscularis propria is the folded structure at the bottom center. | |
Specialty | Gastroenterology |
Ménétrier disease is a rare, acquired, premalignant disease of the stomach characterized by massive gastric folds, excessive mucous production with resultant protein loss, and little or no acid production. The disorder is associated with excessive secretion of
Signs and symptoms
Individuals with the disease present with upper abdominal pain (epigastric), at times accompanied by nausea, vomiting, loss of appetite, edema, weakness, and weight loss. A small amount of gastrointestinal bleeding may occur, which is typically due to superficial mucosal erosions; large volume bleeding is rare.[2] 20% to 100% of patients, depending on time of presentation, develop a protein-losing gastropathy accompanied by low blood albumin and edema.[2][3]
Symptoms and pathological features of Ménétrier disease in children are similar to those in adults, but disease in children is usually self-limited and often follows respiratory infection.[4]
Cause
The cause of Ménétrier disease is unknown, but it has been associated with
While the pathophysiology of Ménétrier disease isn’t fully understood, it is thought that an increase in EGFR signaling — the effect of increased TFG-alpha production responsible for the inhibition of acid production — gives rise to epithelial cell proliferation of the mucosa, causing a direct impact on malabsorption of nutrients, electrolytes, and vitamins in the bowel. [6]
Pathology
With Ménétrier disease, the stomach is characterized by large, tortuous gastric folds in the fundus and body, with the antrum generally spared, giving the mucosa a cobblestone or cerebriform (brain-like) appearance.[5] Histologically, the most characteristic feature is massive foveolar hyperplasia (hyperplasia of surface and glandular mucous cells).[3] The glands are elongated with a corkscrew-like appearance and cystic dilation is common. Inflammation is usually only modest, although some cases show marked intraepithelial lymphocytosis. Diffuse or patchy glandular atrophy, evident as hypoplasia of parietal and chief cells, is typical.[4]
Although ICD-10 classifies it under "Other gastritis" (K29.6), and the lamina propria may contain mild chronic inflammatory infiltrate, Ménétrier disease is not considered a form of gastritis.[3] It is rather considered one of the two most well understood hypertrophic gastropathies; the other being Zollinger–Ellison syndrome.[4]
Diagnosis
The large folds of the stomach, as seen in Ménétrier disease, are easily detected by x-ray imaging following a
Twenty-four-hour pH monitoring reveals hypochlorhydria or achlorhydria, and a chromium-labelled albumin test reveals increased GI protein loss.[5] Serum gastrin levels will be within normal limits.
Other possible causes (eg differential diagnosis) of large folds within the stomach include: Zollinger-Ellison syndrome, cancer, infection (cytomegalovirus/CMV, histoplasmosis, syphilis), and infiltrative disorders such as sarcoidosis.[3]
Treatment
Cetuximab is the first-line therapy for Ménétrier disease.[2] Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR), and has been shown to be effective in treating Ménétrier disease.[7]
Several medications have been used in the treatment of the condition, with variable efficacy. Such medications include: anticholinergic agents,
Severe disease with persistent and substantial protein loss despite cetuximab may require total removal of the stomach, especially when the disease is debilitating or irretractable or when there is a high risk for developing gastric cancer.[8] Subtotal gastrectomy is performed by some; it may be associated with higher morbidity and mortality secondary to the difficulty in obtaining a patent and long-lasting anastomosis between normal and hyperplastic tissue. In adults, there is no FDA approved treatment other than gastrectomy and a high-protein diet. Cetuximab is approved for compassionate use in the treatment of the disease.[9]
Pediatric cases are normally treated for symptoms with the disease clearing up in weeks to months.
Epidemiology
The average age of onset is 40 to 60 years, and men are affected more often than women.[2] Risk of gastric adenocarcinoma is increased in adults with Ménétrier disease.[4][5]
References
- ^ PMID 17200708.
- ^ ISBN 978-0-07-180216-1.
- ^ ISBN 978-0-07-174890-2.
- ^ ISBN 978-1-4377-2015-0.
- ^ a b c d Kumar et al., Pathologic Basis of Disease, 2e , pg 768[ISBN missing][year missing]
- ^ Toubia N, Schubert ML. Menetrier's Disease. Curr Treat Options Gastroenterol. 2008 Apr;11(2):103-8. doi: 10.1007/s11938-008-0022-x. PMID: 18321437.
- PMID 11106719.
- PMID 26689786.
- PMID 20368185.