Menetrier's disease, a rare disorder of unknown etiology, is characterized by enlarged gastric folds due to mucosal thickening in the gastric body. To date, fewer than 100 pediatric cases have been described. Significant differences between adult and pediatric disease in terms of onset, presentation, course and prognosis have been observed.25,26 In children, the disease often begins abruptly and is usually self-limited, with resolution of clinical features within weeks or months. In contrast, in adults, Menetrier's disease is a persis tent and more severe condition often associated with gastrointestinal bleeding, in most cases requiring surgical resection.
Although this disease has also been reported in the neonatal period, the mean age of onset is 5 years (ranging from 2 days to 17 years). Common features include vomiting, abdominal pain, anorexia, hypoproteinemia and, in some cases, eosinophilia and raised IgE levels. Several studies have confirmed that hypoproteinemia is due to a non-selective increased loss of proteins through the gastric mucosa, occurring in a paracellular fashion via widened tight junctions.27 In childhood, hematemesis and melena occur rarely, whereas in adults the incidence of gastrointestinal bleeding ranges from 20 to 40%.
The etiology of Menetrier's disease is unknown, although its acute presentation and self-limited clinical course in childhood suggest an infectious cause. Nearly 30% of affected children show evidence of CMV infection, either through the presence of characteristic inclusion bodies and CMV antigen in the gastric tissue or by serology.25 It has also been proposed that an increase in both serum IgE levels and the number of peripheral blood eosinophils might be an idiosyncratic antibody-mediated response to the penetration of the gastric mucosa by allergens after the cytopathic effect of CMV on the gastric mucosa.
H. pylori infection has also been reported in children with enlarged gastric folds and protein-losing enteropathy, and its eradication has resulted in disease resolution.28 However, the classic clinical and histological features of Menetrier's disease were absent in all reported cases.
Insights into the disease pathogenesis have been gained through the investigation of the mediators of gastric mucosal growth and function, such as transforming growth factor-a (TGFa). The latter stimulates gastric epithelial cell proliferation and mucin secretion, and inhibits parietal cell acid production, in transgenic mice reproducing many altered mucosal features of Menetrier's disease. As in adult patients, elevated levels of TGFa have been found in gastric mucosal biopsies taken from children with Menetrier's disease, suggesting a role for this polypeptide in the development and progression of the disesase.29
Upper gastrointestinal X-ray series identifies the characteristic gastric rugae hypertrophy, predominantly in the fundus and in the corpus of the stomach. Thickened gastric mucosal folds have also been demonstrated by additional diagnostic imaging modalities, such as ultrasound and computed axial tomography. Endoscopy and histology should be performed in all patients to confirm the diagnosis, to search for the pathogen and to exclude different diagnoses, such as eosinophilic gastritis, primary gastric lymphoma, gastric carcinoma, Crohn's disease of the stomach and other conditions in which hypertrophic gastric rugae occur. Endoscopy shows swollen gastric folds predominantly in the greater curvature of the stomach or within the entire body region of the stomach, large quantities of gelatinous mucus and, less commonly, multiple areas of focal erosions in the fundus. Histology usually shows considerable elongation and complexity of the superficial epithelium, so-called foveolar hyperplasia (gastric pit), with reduction of chief and parietal cell glands and often with cystic dilatation, which may extend into the submucosa. An inflammatory infiltrate of eosinophils, neutrophils, lymphocytes and, occasionally, plasma cells is found in the edematous lamina propria.
Typical endoscopic findings are 'beefy' redness or erythema and, occasionally, erosions, but the presence of bile in the stomach during endoscopy does not have clinical significance. The distinctive histological features, also defined as 'chemical gastropathy', include foveolar elongation, complexity and hypercellularity, together with edema, vasodilatation and a paucity of acute and chronic inflammatory cells in the lamina propria.31 These findings do not correlate with gastric bile concentration.
The diagnosis of bile reflux gastropathy should be considered in adults with abdominal pain and bile-stained vomiting, who had previously undergone partial gastric resection or drainage procedures, even though reflux of duodenal contents has been linked to the development of a number of pathological gastric conditions, such as nonspecific gastritis, gastric ulcer, gastric carcinoma and non-ulcer dyspepsia. In adults, an association between bile reflux and intestinal metaplasia in the gastric and cardiac mucosa has been reported, suggesting that the latter represents a defense response against a sustained adverse environment, in the same way that gastric metaplasia develops in the duodenum when subjected to a high acid load.32
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