Ménétrier's disease: Difference between revisions
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===History and Symptoms=== | ===History and Symptoms=== | ||
*Common symptoms of Ménétrier's disease include epigastric pain, dyspepsia, nausea and vomiting, anorexia, weight loss, and edema. | *Common symptoms of Ménétrier's disease include epigastric pain, dyspepsia, nausea and vomiting, anorexia, weight loss, and edema. | ||
===Prognosis=== | ===Prognosis=== | ||
Revision as of 21:49, 15 January 2018
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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.
Introduction
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.
Epidemiology and Demographics
Ménétrier's disease is seen more commonly seen in the age group of 30 to 50 years. Men are more commonly affected than females.
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 cells) hyperplasia with edema, and variable degrees of inflammation.
- Hyperplasia of gastric foveolar cells leads to excessive mucus production and enlarged gastric folds. The gastric pits are elongated and tortuous.
- 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, 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 associated with juvenile polyposis can lead to a mixed hypertrophic/polypoid gastropathy.
- A dominant 1244_1247delACAG mutation of SMAD4 was identified in each of the subjects with JPS as well as in each of the subjects with MD. (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).
Gross pathology
- Polypoid gastric folds
- Large cobblestone or cerebriform gastric folds
Microscopic pathology
- Irregular hypertrophic mucosal folds
- Mucosa have swollen, spongy appearance subdivided by creases
- In rare cases, Ménétrier's disease may have hyperplastic gastric polyps
- Decreased parietal and chief cells with replacement by mucous glands.
- Intraepithelial lymphocytosis
- Glandular tortuosity and dilation,
- Marked reduction in parietal cell number
Associated conditions
- H.pylori infection
- CMV gastritis
- HIV
- Gastric cancer
- Pulmonary infections
- Thrombotic conditions
Similar conditions
Conditions that may present with enlarged gastric folds other than Ménétrier's disease include Zollinger Ellison syndrome, inflammatory gastritis, gastric adenomas (lymphoma, carcinoma), granulomatous gastritis, gastric varices, and Zollinger Ellison syndrome 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 | + |
Diagnostic Criteria
- 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 typical gastric mucosal changes and biopsy establishes the histopathological variant of Ménétrier's disease and also 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.
Risk Factors
Overstimulation by pituitary, hypothalamic, or vagal stimuli.
History and Symptoms
- Common symptoms of Ménétrier's disease include epigastric pain, dyspepsia, nausea and vomiting, anorexia, weight loss, and edema.
Prognosis
The mean age at diagnosis is 5 yr (range: 2 days-17 yr) Ménétrier's disease usually lasts 2-14 wk, 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 with positive GI bleeding.
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.
Electrocardiogram
There are no ECG findings associated with Ménétrier's disease.
X-ray
A barium swallow 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.
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with Ménétrier's disease.
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.
MRI
There are no MRI findings associated with [disease name].
OR
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
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.
Other Diagnostic Studies
There are no other diagnostic studies associated with [disease name].
OR
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
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