Ménétrier's disease: Difference between revisions
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Tthe mainstay of therapy for Ménétrier's disease is supportive care with intravenous albumin (if symptomatic) and parenteral nutritional supplementation. However, some benefit has also been observed with the use of anticholinergic drugs, acid suppression, octreotide and H. pylori eradication. | Tthe mainstay of therapy for Ménétrier's disease is supportive care with intravenous albumin (if symptomatic) and parenteral nutritional supplementation. However, some benefit has also been observed with the use of anticholinergic drugs, acid suppression, octreotide and H. pylori eradication. | ||
==Surgery== | |||
Surgery is not the first-line treatment option for patients with Ménétrier's disease. Surgery (subtotal/total gastrectomy) is usually reserved for patients with either massive protein loss unresponsive to medical therapy or with dysplasia or carcinoma. | Surgery is not the first-line treatment option for patients with Ménétrier's disease. Surgery (subtotal/total gastrectomy) is usually reserved for patients with either massive protein loss unresponsive to medical therapy or with dysplasia or carcinoma. | ||
Revision as of 17:49, 17 January 2018
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]
Synonyms and keywords:
Overview
Ménétrier's disease (also known as hyperplastic hypersecretory gastropathy and giant hypertrophic gastropathy and named after a French physician Pierre Eugène Ménétrier, 1859-1935), is a disorder in which the gastric mucosal folds (rugae) are enlarged[1] (and the total weight of the stomach is increased), making the surface of the stomach look a bit like the brain gyri. The altered gastric mucosa secretes massive amounts of mucus, resulting in low plasma protein levels. The tissue may be inflamed and may contain ulcers. The disease also causes glands in the stomach to waste away and causes the body to lose fluid containing a protein called albumin.
There are two forms of the disease: a childhood form and an adult form. The childhood form has a better prognosis. It affects boys and girls equally, most often after they have a viral illness caused by cytomegalovirus (CMV) or a bacterial infection caused by Helicobacter pylori. Children are not born with this disease, and it is not passed from parents to their children.[2]. The adult form linked with overexpression of transforming growth factor alpha (TGF-α). The adult variety is four times more common in men, primarily affecting men between ages 30 and 60.
The presenting symptoms are
- pain after the meal (=postprandial), relieved by antacids, is very usual
- weight loss, cachexia
- peripheral edema, ascites
- anemia symptoms secondary to blood loss
Ménétrier's disease increases a person's risk of stomach cancer.[3]
Microscopically, the disease is characterized by hyperplasia of the crypts, which are elongated and may appear cystic or corkscrew-like. Since it predisposes to stomach cancer, periodic endoscopic surveillance is mandated. CMV-related Ménétrier is often self-limited.
The disease must be diagnosed by x-ray (rare) or endoscopy and biopsy of the stomach. In adults, treatment may include medications to relieve ulcer symptoms and treat inflammation, and a high-protein diet. Part or all of the stomach may need to be removed if the disease is severe. Pediatric cases are normally treated for symptoms with the disease clearing up in weeks to months.
Other forms of hyperplastic gastropathy include Zollinger-Ellison syndrome.
Overview
Ménétrier's disease is a rare, idiopathic, premalignant disease of the mucous glands of the stomach characterized by massive gastric folds. The most commonly involved location is the fundus and corpus of the stomach. Ménétrier's disease is also known as cystic gastritis, giant hypertrophic gastritis, giant mucosal hypertrophy and hyperplastic gastropathy.
Historical Perspective
In 1888, Pierre Ménétrier, a French pathologist coined the term Ménétrier's disease after describing mucosal hypertrophy involving part or all of the stomach.
Classification
There is no established system for the classification of Ménétrier's disease.
Pathophysiology
The exact pathogenesis of Ménétrier's disease is not fully understood. However, it is thought that Ménétrier's disease is often due to excessive secretion of transforming growth factor alpha (TGF-α).(PMID 18321437) seen especially in infections such as CMV, H.pylori and herpes simplex.
- Overproduction of transforming growth factor-α leads to increased signaling of the epidermal growth factor receptor (EGFR), a transmembrane receptor with tyrosine kinase activity.
- Upon activation, the EGFR activates a series of intracellular signaling pathways that leads to increased cell proliferation.
- Excessive secretion of TGF-α may lead to selective expansion of gastric foveolar cell (surface mucous cell hyperplasia) with edema, and variable degrees of inflammation.
- Hyperplasia of gastric foveolar cells leads to enlarged gastric folds with gastric pits being elongated and tortuous. In addition, there is also excessive mucus production.
- Other gastric glands such as chief or parietal cells are replaced by mucus-secreting cells leading to decreased effective gastric acid production.
- In Ménétrier's disease, there is widening of gap junctions and tight junctions between cells as compared to healthy subjects, and it is believed that proteins traverse from the gastric mucosa into the gastric lumen through these widened spaces. Hence, an increase in intracellular permeability results in protein-losing enteropathy.
- In a nutshell, mucosal hyperplasia with decreased number of chief and parietal cells leads to excessive mucus production, protein loss from the stomach and subsequent hypochlorhydria or achlorhydria. However, it may be noted that Ménétrier's disease is typically but not always associated with protein-losing gastropathy and hypochlorhydria.
Genetics
- Genes involved in the pathogenesis of Ménétrier's disease include mutation in SMAD4 gene (associated with juvenile polyposis. Mutation in SMAD4 gene may lead to a mixed hypertrophic/polypoid gastropathy. A recent study showed that a dominant 1244_1247delACAG mutation of SMAD4 was identified in each of the subjects with juvenile polyposis and in Ménétrier's disease. (PMID 27375208)
- Overproduction of TGF-α leads to overactivation of EGF which may lead to hyperplasia of surface mucous cells.
- Some researchers suggest a unifying hypothesis which suggest TGF-β–SMAD4 pathway inactivation and TGF-α overexpression related to Hp infection ultimately leads to Ménétrier's disease (PMID 22748914).
Associated conditions
- H.pylori infection
- CMV gastritis
- HIV
- Gastric cancer
- Pulmonary infections
- Thrombotic conditions
Gross pathology
- Polypoid and hypertrophic gastric folds
- Large cobblestone or cerebriform gastric folds
- Mucosa have swollen, spongy appearance subdivided by creases
- In rare cases, Ménétrier's disease may have hyperplastic gastric polyps
Microscopic pathology
- Decreased parietal and chief cells
- Intraepithelial lymphocytosis
- Glandular tortuosity and dilation
- Marked reduction in parietal cell number with replacement by mucous glands
Causes
Ménétrier's disease may be caused by over expression of transforming growth factor alpha (TGF-α)(PMID 18321437) seen especially with infections such as CMV, H.pylori and herpes simplex.
Differentiating Ménétrier's disease from Other Diseases
Ménétrier's disease must be differentiated from other conditions that presents with enlarged gastric folds such as Zollinger Ellison syndrome, inflammatory gastritis, granulomatous gastritis, gastric adenomas (lymphoma/carcinoma), and hereditary conditions (such as Familial Adenomatous Polyposis).
Disease | Age of onset | Risk factors | Gastric area involved | Type of gastric glands involved | Inflammatory cells | Symptoms | Progression to malignancy | |||
---|---|---|---|---|---|---|---|---|---|---|
Nausea | Vomitting | Abdominal pain | Other features | |||||||
Menetrier's Disease | 40-60s | H.pylori infection
CMV gastritis |
Body & fundus | Mucosal cells | Lymphocytes | + | + | + | Peripheral edema | + |
Zollinger Ellison syndrome | 50s | MEN 1 syndrome | Fundus | Parietal and mucosal cells | Neutrophils | + | + | + | Recurrent ulcers | - |
Inflammatory & hyperplastic polyps | 50s | Gastritis and H.pylori | Antrum | Mucosal cells | Neutrophils and lymphocytes | + | + | + | Rectal bleeding with diarrhea or constipation | +/- |
Granulomatous gastritis | Variable | History of prior surgery | Body | Mucosal cells | Neutrophils and lymphocytes | + | + | + | Gastric outlet obstruction | - |
Familial adenomatous polyposis | 50s | Mutation in APC gene | Body & fundus | Parietal cells | None | - | - | - | Asymptomatic to bleeding per rectum | + |
Adenomas (gastric) | 60s | Chronic gastritis and intestinal metaplasia | Antrum | Dysplastic cells | Variable | + | + | + | Early satiety | + |
Epidemiology and Demographics
Ménétrier's disease is seen in both children and adults. In children Ménétrier's disease affects boys and girls equally. In adults, Ménétrier's disease is more commonly seen in the age group of 30 to 50 years with men are more commonly affected than females.
Risk Factors
Common risk factors in the development of Ménétrier's disease includes overstimulation of gastric mucosa by pituitary, hypothalamic, or vagal stimuli.
Diagnosis
- There is no established criteria for the diagnosis of Ménétrier's disease. However, an endoscopic biopsy, chromium-labeled albumin test (GI protein loss), and 24-hour pH monitoring can establish the diagnosis of Ménétrier's disease. Endoscopy shows the typical gastric mucosal changes and biopsy establishes the histopathological variant of Ménétrier's disease. Biopsy is also done to rule out gastric carcinoma or lymphoma.
- The most accurate method to diagnose Ménétrier's disease includes testing such as oesophagogastroduodenoscopy with gastric pH, serum albumin and full-thickness mucosal biopsy of the involved gastric mucosa.
History and Symptoms
Common symptoms of Ménétrier's disease include epigastric pain after meals, dyspepsia, nausea and vomiting, anorexia, weight loss, and edema.
Prognosis
In children, Ménétrier's disease usually lasts for 2-14 weeks, with complete resolution being the rule.
Physical Examination
Patients with Ménétrier's disease usually appear fatigued. Common physical examination findings of patients with Ménétrier's disease includes abdominal tenderness, peripheral edema and with signs of iron deficiency anemia such as pallor and brittle nails.
Laboratory Findings
Laboratory findings consistent with the suggestive of Ménétrier's disease include hypoalbuminemia and hypochlorhydria resulting from protein-losing enteropathy and decreased acid secretion respectively.
X-ray
A barium meal may be helpful in the diagnosis of Ménétrier's disease. Findings on an upper GI series suggestive of Ménétrier's disease include thickened and lobulated gastric folds located in gastric fundus and body.
CT scan
Abdominal CT scan may be helpful in the diagnosis of Ménétrier's disease. Findings on CT scan suggestive of Ménétrier's disease include massive lobulated gastric folds. An important feature of Ménétrier's disease which differentiates it from gastric carcinoma includes the presence of pliable gastric folds as compared to rigid and aperistaltic gastric folds seen in carcinoma.
Other Imaging Findings
Endoscopy may be helpful in the diagnosis of Ménétrier's disease. Findings on an endoscopy suggestive of Ménétrier's disease include enlarged, nodular and coarse gastric folds.
Medical Therapy
Tthe mainstay of therapy for Ménétrier's disease is supportive care with intravenous albumin (if symptomatic) and parenteral nutritional supplementation. However, some benefit has also been observed with the use of anticholinergic drugs, acid suppression, octreotide and H. pylori eradication.
Surgery
Surgery is not the first-line treatment option for patients with Ménétrier's disease. Surgery (subtotal/total gastrectomy) is usually reserved for patients with either massive protein loss unresponsive to medical therapy or with dysplasia or carcinoma.
References
Additional Resources
- Rubin's Pathology, Clinicopathological Foundations of Medicine, 4th edition, Rubin, Gorstein, Rubin, Schwarting, Strayer. Lippincott Williams & Wilkins. ISBN 0-7817-4733-3