Tuesday, February 05, 2008
Questions and Answers About the Diagnosis and Treatment of Mastocytic Enterocolitis or Mastocytic Inflammatory Bowel Disease (MIBD)
WHAT IS MASTOCYTIC ENTEROCOLITIS?
Mastocytic enterocolitis (entero-small intestine, colitis- colon+ -itis or inflammation) is a relatively new condition inflammatory bowel disease to be recognized. It is characterized by increased number of mast cells in the intestine surface lining, also known as the mucosa. Mast cells are a type of blood cell. They are involved in various immune and infection fighting processes in the body. In the gastrointestinal tract typically around 12 mast cells can be seen per high power field (40X magnification) under the microscope. In mastocytic enterocolitis is now defined by the presence of 20 or more mast cells per HPF in the small intestine and/or colon.
WHAT ARE MAST CELLS AND WHY ARE INCREASED NUMBERS PRESENT IN MASTOCYTIC ENTEROCOLITIS?
Mast cells are present in the blood, bone marrow and various tissues throughout the body. They originally arise from the bone marrow and migrate to other areas as needed. Rat studies have previously confirmed that stress increases mast cells in the intestine and causes leaky gut. Mast cells seem to have several important functions in the gut including not only immune function but also gut nerve function. Mast cell activation can result in increase gut contractions or decrease gut contractions. A recent study confirms that the stress hormone corticotropin-releasing hormone (CRH) stimulates mast cells in the human colon through receptors present on the mast cells and can trigger their release of chemicals from granules. Increase mast cells are found in association with other inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease as well as in celiac disease, “allergic esophagus” or eosinophilic esophagitis, and in post-infectious irritable bowel syndrome (IBS). Mast cells are increasingly being mentioned in the predisposition, subsequent development or progression of these other conditions as well as many cases of IBS.
WHAT ARE THE SYMPTOMS?
The classic symptoms of mastocytic enterocolitis are cramping quality abdominal pain and urgency with diarrhea. However, constipation, nausea, vomiting and non-GI symptoms are also commonly reported or associated such as flushing or feeling hot, poor appetite, and headaches. Since mast cells release mediators that can affect the nerves of the gut resulting in increase contraction or reduced contractions, it makes sense that either diarrhea or constipation can occur. In fact, a recent study confirmed that mast cell release of their various chemical mediators is the cause of intestinal paralysis or delayed function after abdominal or intestinal surgery known as postoperative ileus. The mechanical stimulation of the surgeon handling the intestines during traditional open abdominal surgery has been shown to trigger the release histamine and other chemicals present in mast cell granules. This is what is believed to cause the gut fail to normally contract initially after surgery.
WHAT CAUSES MASTOCYTIC ENTEROCOLITIS?
It appears that infections and stress are causes. Food allergy and sensitivity are also suspected. There may be a genetic risk, in particular DQ genetic risk common to celiac disease. Leaky gut or increased gut permeability is a risk factor and the presence of increase mast cells in the gut. This predisposes or increases leaky gut so that a vicious cycle may result. Altered gut microbes likely also play a role. Either having a gastrointestinal infection or receiving antibiotics for an infection appears to be a risk factor. Mast cell levels tend to vary in the gut. They are increased the most during active symptoms, especially periods of stress and altered gut permeability.
HOW IS MASTOCYTIC ENTEROCOLITIS DIAGNOSED?
The diagnosis is made by determining that there are 20 or more mast cells per high power field in the superficial intestinal lining or mucosa. However, in order to see these mast cells, which are otherwise “covert” or hidden behind other cells, special stains are required. Until recently these stains were either expensive or not readily available. Mast cells in mucosa contain an enzyme tryptase that stains with a special immunohistochemical making the mast cells easy to see and count. However, these stains typically must be requested by the doctor obtaining intestinal biopsies at the time of endoscopic procedure is performed or by alerting the pathologist that the condition is suspected. The stains can also be performed on tissue previously obtained by special request as long as the tissue is available and the pathology department has the stain.
HOW IS MASTOCYTIC ENTEROCOLITIS TREATED?
The usual treatment is combinations of antihistamines and mast cell stabilizers along with a search for food allergies and intolerances. Since one of the main chemical mediators released from the granules in mast cells is histamine antihistamine medications are often helpful in reducing symptoms. Histamine receptors come in two types, type 1 and type II. Type I histamine receptors are typically found in respiratory and skin tissues and type I antihistamines are commonly used to treat allergic reactions. Common type I antihistamine or H1 blockers are Benadryl, Zirtec, Allegra, and Claritin, etc. There are type II histamine receptors found in the digestive tract, especially the stomach where their stimulation results in increase acid production and competitive inhibition by type II antihistamines suppresses or reduces stomach acid production. The common type II antihistamine or H2 blocker medications are Zantac, Tagamet, and Pepcid. Typically, both type I and type II antihistamines are used and help reduce abdominal pain and diarrhea in mastocytic enterocolitis.
Mast cell stabilizing medications also exist but the only commonly commercially available one is sodium Cromalyn. It is used in eye drops, nasal sprays and for inhalation for eye and nasal allergies and asthma. For the treatment of systemic mastocytosis related GI symptoms and mastocytic enterocolitis, sodium Cromalyn is commercially available in the brand name preparation Gastrocrom. Gastrocrom comes in a dosage form of 100 mg per 5 ml concentration packaged in a box of 96 5 ml ampules. The usual dose is 200 mg orally four times a day for 4-6 weeks.
Since food allergies and food intolerances may be a trigger, testing for both is recommended. Also, because stress is related, stress reduction or treatment is recommended. Avoidance of things that increase gut permeability or leaky gut and promotion of increase tight junctions by use of probiotics also makes sense though these treatments have not been formally tested specifically in mastocytic enterocolitis.
WHAT IS THE LONGTERM PROGNOSIS OF MASTOCYTIC ENTEROCOLITIS?
This is not known. However, mast cells are dynamic and appear to regress from the gut. Treatment with antihistamines and mast cell stabilizers do reduce symptoms in most patients. Avoidance of foods determined to cause allergic reactions or chemical mediator release seems to help also. It is no known whether mastocytic enterocolitis is a precursor or transition to other inflammatory bowel diseases such as ulcerative colitis, Crohn’s disease, Celiac disease or eosinophilic gastrointestinal disorders. Genetics, immune status, intestinal microbe make up, and degree of gut inflammation or injury with resultant leaky gut are all likely important factors regarding risk of development of other inflammatory conditions, recovery or improvement.
The FO et al. “Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus.” Gut 2008; 57:33-40
Wallon, C et al. “Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro.” Gut 2008; 57:50-58.
Jakate, S. “Mastocytic Enterocolitis: Increased mucosal mast cells in chronic intractable diarrhea.” Arch Pathol Lab Med 2006; 130:362-367.
NIH website overview of mastocytosis
The Mastocytic Society
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Dr. Scot Michael Lewey
“Dr. Celiac, the food doc”
1699 Medical Center Point
Colorado Springs CO 80907