Ménétrier's disease
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: Cystic gastritis; Giant hypertrophic gastritis; Giant mucosal hypertrophy and hyperplastic gastropathy.
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. It is thought that Ménétrier's disease is often due to excessive secretion of transforming growth factor alpha (TGF-α). The altered gastric mucosa secretes massive amounts of mucus, resulting in low plasma protein levels (albumin) with variable degree of inflammation.
Historical Perspective
In 1888, Pierre Ménétrier, a French pathologist coined the term Ménétrier's disease after describing patients with mucosal hypertrophy involving part or all of the stomach in his journal "Archives Physiologie Normale et Pathologique".[1]
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 (in children & adults) is often due to excessive secretion of transforming growth factor alpha (TGF-α). In children, Ménétrier's disease is especially seen with infections such as CMV, Helicobacter pylori and herpes simplex.[2][3][4][5][6][7]
- 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. The inflammation may lead to superficial erosion of gastric mucosa or ulceration.
- Hyperplasia of gastric foveolar cells leads to enlarged gastric folds with elongated and tortuous gastric pits. 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.
- Ménétrier disease has an insidious onset with progressive features and believed to increase the risk of gastric cancer, but the magnitude of this risk is uncertain.
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.[8]
- Overproduction of TGF-α leads to overactivation of EGFR 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 Helicobacter pylori infection ultimately leads to Ménétrier's disease.[4]
Associated conditions
- Helicobacter pylori infection
- CMV gastritis
- HIV
- Gastric cancer
- Pulmonary infections
- Thrombotic conditions
- Sclerosing cholangitis
- Ankylosing spondylitis
Gross pathology
- Polypoid and hypertrophic gastric folds
- Large cobblestone or cerebriform gastric folds
- 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) seen especially with infections such as CMV, H.pylori and herpes simplex.[2]
Differentiating Ménétrier's disease from Other Diseases
Ménétrier's disease must be differentiated from other conditions that presents with enlarged/massive gastric folds such as Zollinger-Ellison syndrome, inflammatory gastritis, granulomatous gastritis, gastric adenomas (lymphoma/carcinoma), and hereditary conditions (such as Familial Adenomatous Polyposis).[9][10][11][12]
| Disease | Age of onset | Risk factors | Distribution | 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 | Diffuse | Body & fundus | Mucosal cells | Lymphocytes | + | + | + | Peripheral edema | + |
| Zollinger-Ellison syndrome | 50s | MEN 1 syndrome | Diffuse | Fundus | Parietal and mucosal cells | Neutrophils | + | + | + | Recurrent ulcers | - |
| Inflammatory & hyperplastic polyps | 50s | Gastritis and H.pylori | Focal | Antrum | Mucosal cells | Neutrophils and lymphocytes | + | + | + | Rectal bleeding with diarrhea or constipation | +/- |
| Granulomatous gastritis | Variable | History of prior surgery | Diffuse | Body | Mucosal cells | Neutrophils and lymphocytes | + | + | + | Gastric outlet obstruction | - |
| Familial adenomatous polyposis | 50s | Mutation in APC gene | Variable | Body & fundus | Parietal cells | None | - | - | - | Asymptomatic to bleeding per rectum | + |
| Adenomas (gastric) | 60s | Chronic gastritis and intestinal metaplasia | Variable | 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 four times more commonly affected than women.[13][14][15]
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 with biopsy can identify the accurate histopathology and depict the typical gastric mucosal changes of Ménétrier's disease. Biopsy is also necessary to rule out gastric carcinoma or lymphoma.[16]
- The most accurate method to diagnose Ménétrier's disease includes testing such as esophagogastroduodenoscopy 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 is usually from CMV infection and lasts for 2-14 weeks, with complete resolution being the rule. In adults, untreated Ménétrier's disease may increase a patient's risk of stomach cancer. Thus, a periodic endoscopic surveillance is necessary. [17]
Physical Examination
Patients with Ménétrier's disease usually appear fatigued and cachexic. Common physical examination findings of patients with Ménétrier's disease includes abdominal tenderness, peripheral edema and with signs of iron deficiency anemia (secondary to blood loss from ulcers) such as pallor and brittle nails. Patients with prolonged Ménétrier's disease may also have ascites and abdominal distension from protein loss.
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. Other tests include complete blood count and metabolic panel to determine the severity of the disease.[16]
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
The 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
- ↑ Coffey RJ, Tanksley J (2012). "Pierre Ménétrier and his disease". Trans. Am. Clin. Climatol. Assoc. 123: 126–33, discussion 133–4. PMC 3540591. PMID 23303980.
- ↑ 2.0 2.1 Toubia N, Schubert ML (2008). "Menetrier's Disease". Curr Treat Options Gastroenterol. 11 (2): 103–8. PMID 18321437.
- ↑ Bencharif L, Cathébras P, Bouchou K, Gouilloud S, Fichtner C, Rousset H (1998). "[Exudative gastroenteropathy revealing primary CMV infection in an immunocompetent adult]". Rev Med Interne (in French). 19 (4): 288–90. PMID 9775159.
- ↑ 4.0 4.1 Piepoli A, Mazzoccoli G, Panza A, Tirino V, Biscaglia G, Gentile A, Valvano MR, Clemente C, Desiderio V, Papaccio G, Bisceglia M, Andriulli A (2012). "A unifying working hypothesis for juvenile polyposis syndrome and Ménétrier's disease: specific localization or concomitant occurrence of a separate entity?". Dig Liver Dis. 44 (11): 952–6. doi:10.1016/j.dld.2012.05.019. PMID 22748914.
- ↑ Occena RO, Taylor SF, Robinson CC, Sokol RJ (1993). "Association of cytomegalovirus with Ménétrier's disease in childhood: report of two new cases with a review of literature". J. Pediatr. Gastroenterol. Nutr. 17 (2): 217–24. PMID 8229553.
- ↑ Mosnier JF, Flejou JF, Amouyal G, Gayet B, Molas G, Henin D, Potet F (1991). "Hypertrophic gastropathy with gastric adenocarcinoma: Menetrier's disease and lymphocytic gastritis?". Gut. 32 (12): 1565–7. PMC 1379265. PMID 1773969.
- ↑ Haot J, Bogomoletz WV, Jouret A, Mainguet P (1991). "Ménétrier's disease with lymphocytic gastritis: an unusual association with possible pathogenic implications". Hum. Pathol. 22 (4): 379–86. PMID 2050372.
- ↑ Burmester JK, Bell LN, Cross D, Meyer P, Yale SH (2016). "A SMAD4 mutation indicative of juvenile polyposis syndrome in a family previously diagnosed with Menetrier's disease". Dig Liver Dis. 48 (10): 1255–9. doi:10.1016/j.dld.2016.06.010. PMID 27375208.
- ↑ Huh WJ, Coffey RJ, Washington MK (2016). "Ménétrier's Disease: Its Mimickers and Pathogenesis". J Pathol Transl Med. 50 (1): 10–6. doi:10.4132/jptm.2015.09.15. PMC 4734964. PMID 26689786.
- ↑ Blackstone MM, Mittal MK (2008). "The edematous toddler: a case of pediatric Ménétrier disease". Pediatr Emerg Care. 24 (10): 682–4. doi:10.1097/PEC.0b013e3181887e89. PMID 19240670.
- ↑ Wolfsen HC, Carpenter HA, Talley NJ (1993). "Menetrier's disease: a form of hypertrophic gastropathy or gastritis?". Gastroenterology. 104 (5): 1310–9. PMID 8482445.
- ↑ Tan DT, Stempien SJ, Dagradi AE (1971). "The clinical spectrum of hypertrophic hypersecretory gastropathy. Report of 50 patients". Gastrointest. Endosc. 18 (2): 69–73. PMID 5316105.
- ↑ http://www.madisonsfoundation.org/content/3/1/display.asp?did=413
- ↑ Baker A, Volberg F, Sumner T, Moran R (1986). "Childhood Menetrier's disease: four new cases and discussion of the literature". Gastrointest Radiol. 11 (2): 131–4. PMID 3514352.
- ↑ Gandhi M, Nagashree S, Murthy V, Hegde R, Viswanath D (2001). "Menetrier's disease". Indian J Pediatr. 68 (7): 685–6. PMID 11519296.
- ↑ 16.0 16.1 Rich A, Toro TZ, Tanksley J, Fiske WH, Lind CD, Ayers GD, Piessevaux H, Washington MK, Coffey RJ (2010). "Distinguishing Ménétrier's disease from its mimics". Gut. 59 (12): 1617–24. doi:10.1136/gut.2010.220061. PMC 3020399. PMID 20926644.
- ↑ http://www.mamashealth.com/stomach/menetrier.asp
Additional Resources
- Rubin's Pathology, Clinicopathological Foundations of Medicine, 4th edition, Rubin, Gorstein, Rubin, Schwarting, Strayer. Lippincott Williams & Wilkins. ISBN 0-7817-4733-3