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Menetrier Disease


Menetrier Disease

Article Author:
Meghana Gore
Article Author:
Kamna Bansal
Article Editor:
Nagesh Jadhav
Updated:
9/23/2020 12:43:45 PM
For CME on this topic:
Menetrier Disease CME
PubMed Link:
Menetrier Disease

Introduction

Menetrier disease is a rare disorder that is characterized by giant mucosal folds in the proximal part of the stomach, diminished acid secretion, and a protein-losing state with hypoalbuminemia. Other names for Menetrier disease are hypoproteinemic hypertrophic gastropathy and giant hypertrophic gastritis.[1] 

This condition is common in middle-aged men. The age group affected is generally between 30 years to 60 years. It is less commonly described in females and children. In adults, the condition is often progressive. The etiopathogenesis of Menetrier disease is not entirely understood. It affects mainly the proximal part of the stomach (body and fundus) and spares the distal portion (antrum).[2]

Etiology

The exact etiology of Menetrier disease is unclear. However, researchers think the condition is an acquired illness rather than an inherited one. In children, a self-limited variant of Menetrier disease is observed, which is associated with cytomegalovirus infection.[3] Similarly, in adults, it is associated with Helicobacter pylori infection.[4][5] It is hypothesized that overexpression of the transforming growth factor (TGF)-alpha in superficial gastric epithelium may play a role in the etiopathogenesis.[6] Rare cases in families indicate some genetic association behind the disease as well.[7]

Epidemiology

Menetrier disease is a rare condition, and the prevalence is unknown. To date, less than 1000 cases are reported. Males are affected more than females. It affects adults older than 30 years. The usual age of onset of symptoms of Menetrier disease is 55 years.[8] As per one study, 5 to 10-year survival after diagnosis was 72.7% and 65%, respectively. 8.9% of patients developed gastric cancer after 10 years of follow up.[9]

Pathophysiology

The pathophysiology of Menetrier disease is not fully understood. It is thought that an increase in the signaling of the epidermal growth factor receptor (EGFR), which is the effect of increased production of TGF-alpha, leads to the proliferation of epithelial cells of the mucosa. TGF-alpha is a ligand that activates the EGFR and stimulates the growth of epithelial cells. Excess epithelial cells produce abundant mucus. Under the effect of TGF-alpha, there is decreased acid production. The decrease in acid is due to a direct impact on the parietal cells and indirectly via stimulation of somatostatin release. Hypersecretion of mucus leads to malabsorption of nutrients, electrolytes, and vitamins in the small bowel. Malabsorption of essential nutrients is manifested as the clinical syndrome of a protein-losing gastropathy.[1][10]

Histopathology

Pierre Ménétrier compared the macroscopic appearance of the pathognomic thickened gastric mucosa related to disease to cerebral convolutions (gyri). On endoscopy, this is evident by marked enlargement of gastric folds and rugae. On histopathological examination, foveolar hyperplasia, oxyntic glands atrophy, reduction in parietal (acid-producing cells) and chief (pepsinogen- producing ) cells, and cystic dilation of pits are seen. The overall linear architecture is usually maintained. Edema and hyperplasia of smooth muscle in the lamina propria are observed.[2][11]

History and Physical

In adults, Menetrier disease usually has a subtle onset with progressive features. The most common clinical features are epigastric pain (65%), followed by fatigue (60%), anorexia (45%), weight loss (45%), edema (38%), and vomiting (38%).[12] Other symptoms are nausea, diarrhea, and gastrointestinal bleeding related to gastric erosion and ulcers.[13] Rarely a patient may have gastroduodenal intussusception as a presentation.[14] Other clinical features that are associated with hypoalbuminemia from a protein-losing enteropathy like ascites, pleural effusion, and pericardial effusion can also be seen.[15]

In children, Menetrier disease is acute in onset and spontaneously resolves within a few weeks. Childhood Menetrier disease is associated with cytomegalovirus (CMV). In adults, it is associated with H. pylori infection.[16]

Menetrier disease is weakly associated with ulcerative colitis.[15]

Evaluation

Diagnosis can be reached by obtaining a biopsy showing extreme foveolar hyperplasia with atrophic changes in glandular epithelium along with remarkable enlargement of gastric rugae evident on esophagogastroduodenoscopy (EGD) and barium esophagogram. Endoscopy reveals giant gastric folds, superficial punctate erosions, and erythema. It is recommended to obtain a full-thickness mucosal biopsy of the involved mucosa, which will identify the loss of a deep glandular component along with other typical findings.[17]

A barium study shows markedly enlarged folds along the greater curvature of the stomach, sparing the antrum. Barium is diluted due to excess mucus secretion, which is seen as an impaired mucosal coating. On the contrast-enhanced computed tomography (CT) images, diffuse gastric mucosal thickening is seen.[14][18]

The histopathological exam includes characteristic findings of mucosal architecture for parallelism of glands and foveolar hyperplasia of surface mucous cells. A significant reduction in parietal cells, dilation of glands, increased eosinophils and plasma cells, edema, and smooth muscle hyperplasia is observed.[19]

Laboratory evaluation must include a complete blood count, including a white blood cell (WBC) count, hemoglobin, hematocrit, and platelet counts, a complete metabolic panel, serum gastrin, H. pylori, and CMV serology. Typical laboratory findings include lymphopenia, reduced levels of globulin, albumin, alpha-1-antitrypsin, cholesterol, fibrinogen, and ceruloplasmin, elevated serum gastrin, and iron deficiency anemia.[20][21]

Treatment / Management

For the treatment of Menetrier disease, clinical trials are lacking, and pharmacological therapies have shown inconsistent benefits.

The supportive treatments that are prescribed are a high-protein diet, proton pump inhibitors, and replacement of micronutrients.

Treatment of H. pylori and CMV is recommended if the tests for respective infections are positive. Eradication of H.pylori has been shown to improve disease conditions in a few patients. Similarly, treatment with ganciclovir has been shown to be effective in some CMV related cases.[22]

Octreotide, a somatostatin analog, has shown to be beneficial in case reports. It acts by modulating the TGF-alpha - EGFR pathway, which is the underlying pathogenic mechanism. A dose of 100 to 600 micrograms daily subcutaneously or intravenously or octreotide depot formulation 10 to 60 mg intramuscularly every four weeks has been used.[23][24]

In a small case series, patients with severe Ménétrier disease who were treated for one month with cetuximab showed significant improvement in the quality of life as well as biochemical measures. Cetuximab is a recombinant IgG1 monoclonal antibody. Cetuximab binds to the extracellular portion of the EGF receptor, which inhibits the binding of TGF-alpha.[15]

In some instances, in disease progression with severe, intractable abdominal pain, oral intolerance, weight loss, bleeding, or pyloric obstruction, surgery is recommended. Partial and total gastrectomy remains an acceptable means of treatment for cases with persistent and debilitating symptoms or growing concern for gastric cancer development. Total gastrectomy is preferred over partial gastrectomy due to better surgical outcomes.[25][26]

Differential Diagnosis

Zollinger-Ellison syndrome - Which is associated with ectopic secretion of gastrin. The tumor is located in the duodenum or pancreas. Due to excess secretion of gastric acid, there is the development of peptic ulcers in the GI tract. On histopathology examination, there is parietal cell hyperplasia. 

H. pylori gastritis - Evidence of gastritis present, and the H. pylori tests are positive. 

Hypertrophic lymphocytic gastritis - It presents very similar to Menetrier disease. In this condition, on histopathological examination, gastric mucosa shows severe inflammation with predominant intraepithelial lymphocytes.[2]

Hypertrophic hypersecretory gastropathy - There is hypersecretion of all glandular cell types of the stomach. There is excess acid secretion, pepsin, and mucin secretion as well. On histological exam, there is hyperplasia of the foveolar epithelium as well as oxyntic glands.[27]

Gastric polyps - These are more focal than a diffuse disease. They can be numerous and mimic Menetrier disease. 

Gastric adenocarcinoma - On the histopathological exam, it shows dysplasia and neoplastic features, and loss of architecture helps to differentiate it from Menetrier disease.

Infectious etiologies like histoplasmosis, syphilis, tuberculosis, and infiltrative disorders such as sarcoidosis can mimic Menetrier disease.

Prognosis

In children, the disease is self-limited. It may take anywhere from a few weeks to months of the illness to resolve spontaneously. In children, symptoms improve with treatment of CMV infection with ganciclovir.[28]

In adults, the disease is generally progressive. There are few cases of resolution in adults after the treatment of H. pylori infection.[5]

It is suggested that patients with Menetrier disease are at increased risk of malignancies, including primarily gastric carcinoma and gastric lymphoma, so some recommend endoscopic surveillance on a regular basis for early detection of dysplasia or carcinoma.[9]7][9]

Complications

In adults, the disease is progressive and can be associated with significant morbidity and mortality. Complications usually involve malignant transformation, a thromboembolic phenomenon, and gastric outlet obstruction.

Other complications associated are with surgical resection of the stomach, including anastomotic leak and fistula formation, bleeding, etc.

Deterrence and Patient Education

Menetrier disease is a rare disease that presents with common gastrointestinal symptoms like weight loss, nausea, vomiting, abdominal pain, and weight loss. Patients should be educated that no one treatment has been proven effective. A nutrition consult may be useful to teach patients about the importance of a high protein diet. Patients should also be made aware of the potential of malignant transformation, so close follow up with the gastroenterologist is recommended.

Enhancing Healthcare Team Outcomes

Menetrier disease is a rare disease with unknown prevalence. Primary care clinicians need to be aware of this disease as the diagnosis requires referral to a gastroenterologist. As there is no proven treatment for this disease, an interprofessional team approach involving primary clinicians, gastroenterologists, pathologists, and a surgeon is recommended. For milder cases, supportive treatment with the involvement of a dietician to mitigate protein loss is recommended.


References

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