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Stomach

Menetrier Disease

General Discussion

Menetrier disease is a rare disorder characterized by massive overgrowth of mucous cells (foveola) in the mucous membrane lining the stomach, resulting in large gastric folds. The most common symptom associated with Menetrier disease is pain in the upper middle region of the stomach (epigastric pain). The cause of Menetrier disease is unknown.

There is considerable confusion and contradiction in the medical literature regarding disorders involving large gastric folds. The name Menetrier disease is often erroneously used to describe any condition with large gastric folds or as a synonym for giant hypertrophic gastritis (GHG). However, Menetrier disease is not a true form of gastritis. A diagnosis of Menetrier disease should be reserved for individuals with large gastric folds due to overgrowth of mucous cells. There is minimal or no stomach inflammation in Menetrier disease. Because inflammation is minimal or not present, Menetrier disease is classified as a form of hyperplastic gastropathy and not as a form of gastritis. Some researchers believe that Menetrier disease and GHG may be variants of the same disorder or different parts of one disease spectrum.


Signs & Symptoms

The symptoms of Menetrier disease may vary from case to case. Some individuals may not exhibit any symptoms (asymptomatic). The most common symptom is pain in the upper middle region of the stomach (epigastric pain). Less frequent reported symptoms include nausea, vomiting, and diarrhea. In some cases, weight loss and profound loss of appetite (anorexia) may also occur.

An additional variable finding sometimes associated with Menetrier disease is the loss of protein from the circulation into the gastrointestinal tract (protein-losing gastropathy) such as the loss of the protein albumin (hypoalbuminemia). Protein loss may be severe in some cases. Protein loss may result in fluid accumulation (edema), especially in the legs.

Gastrointestinal bleeding has also been reported in some cases of Menetrier disease usually as a result of erosions or ulcers in the stomach lining. Acid secretion by the stomach is often markedly decreased (hypochlorhydria) or absent. Excess mucous secretion in the stomach may also occur.

Some researchers believe that individuals with Menetrier disease have a greater risk of developing gastric cancer than the general population has. However, other researchers do not believe this to be proven with certainty. In some series, there has been an association between Menetrier disease and ulcerative colitis.


Causes

The exact cause of Menetrier disease is unknown. There may be multiple causes. In children, some cases of Menetrier disease may be associated with infection with cytomegalovirus (CMV). The bacterium Helicobacter pylori has been implicated in some adults with Menetrier disease. The exact role, if any that these infections play in the development of Menetrier disease is unknown.

).aSome researchers believe that the large gastric folds that characterize Menetrier disease may result from increased activation of the epidermal growth factor receptor in the stomach by a protein called transforming growth factor-alpha (TGF

In extremely rare cases, siblings of affected patients have developed Menetrier disease as children suggesting a genetic link in these cases. Researchers believe that, in these cases, Menetrier disease may be inherited as an autosomal dominant trait. Genetic diseases are determined by two sets of genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.


Affected Populations

Menetrier disease affects males slightly more often than females. It most often affects adults in their 50s or older. However, a childhood form of the disorder exists. Because of the confusion in the literature regarding the term Menetrier disease, it is difficult to determine its true frequency in the general population.


Related Disorders

Symptoms of the following disorders can be similar to those of Menetrier disease. Comparisons may be useful for a differential diagnosis:

Zollinger-Ellison syndrome (ZES) is a rare, digestive disorder characterized by the development of a tumor (gastrinoma) or tumors that secrete excessive levels of gastrin, a hormone that stimulates production of acid by the stomach. Many affected individuals develop multiple gastrinomas, approximately half to two-thirds of which may be cancerous (malignant). In most cases, the tumors arise within the pancreas and/or the upper region of the small intestine (duodenum). Due to excessive acid production (gastric acid hypersecretion), individuals with ZES may develop peptic ulcers of the stomach, the duodenum, and/or other regions of the digestive tract. Peptic ulcers are sores or raw areas within the digestive tract where the lining has been eroded by stomach acid and digestive juices. Symptoms and findings associated with ZES may include mild to severe abdominal pain; diarrhea; gastroinestinal bleeding; increased amounts of fat in the stools (steatorrhea); and/or other abnormalities. Individuals with Zollinger-Ellison syndrome may have giant gastric folds. (For more information on this disorder, choose “Zollinger-Ellison” as your search term in the Rare Disease Database.)

Lymphocytic gastritis is a rare disorder characterized by inflammation of the stomach due to the accumulation of inflammatory cells in the inner wall (mucosa) of the stomach resulting in abnormally large, coiled ridges or folds that resemble polyps in the inner wall of the stomach (large gastric folds). Many individuals with lymphocytic gastritis do not have symptoms (asymptomatic). Symptoms that may occur include nausea, vomiting, abdominal pain, diarrhea, and weight loss. The exact cause of lymphocytic gastritis is unknown although the disorder has been linked to celiac sprue and also to Helicobacter pylori infection. (For more information on this disorder, choose “lymphocytic gastritis” as your search term in the Rare Disease Database.)

Additional causes of large gastric folds include Helicobacter pylori-associated gastritis, certain infections including syphilis, and various forms of cancer include certain forms of carcinoma or lymphoma. Other rare disorders such as sarcoidosis or Cronkite-Canada disease may also be associated with large gastric folds. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)


Diagnosis

Menetrier disease may be suspected in individuals with large gastric folds. Large gastric folds may be diagnosed by a radiologic study after the patient drinks a barium solution or by an endoscopic exam, a procedure in which a thin, flexible tube (endoscope) is inserted through the mouth and used to examine the interior of the stomach and, if necessary, to obtain tissue samples for microscopic study (biopsy). Histopathologic study of affected stomach tissue obtained by biopsy can support a diagnosis of Menetrier disease. Histopathology is the study of microscopic anatomical changes in diseased tissue.


Standard Therapies

Treatment

Menetrier disease has been treated with anticholergic drugs, acid suppression therapy, and antibiotic therapy directed against H. pylori infection. These therapies have produced inconsistent results. In some cases, a high-protein diet may be recommended to combat protein loss. Albumin transfusions may also be used to replace albumin loss.

Cetuximab (Erbitux) infusions block the epidermal growth factor receptor and have been successful in some patients with Menetrier disease. Cetuximab treatment can improve quality of life, restore gastric acid production and possibly even reduce the thickness of the stomach wall. In a few cases, after cetuximab infusions are discontinued the patient remains well, at least termporarily. Erbitux may cause cardiopulmary arrest, an acne-like rash and low levels of magnesium, and thus patients must be carefully monitored on this treatment.

In severe cases such as those with significant protein loss or a high probability of progression to gastric cancer, partial or total gastrectomy may be necessary. Gastrectomy is the surgical removal of part or all of the stomach.

In children with Menetrier disease linked to cytomegalovirus infection, antiviral medication directed against cytomegalovirus may lead to improvement of symptoms.

Other treatment is symptomatic and supportive.