Monday, February 04, 2008
Mastocytic enterocolitis: A new epidemic, mastocytic inflammatory bowel disease (MIBD), may mimic IBS and be related to stress
Mastocytic enterocolitis is a new entity that has been described more recently as a condition characterized by increase mast cells of 20 or more per high-powered field in the duodenum or colon. Jakate et al. described 47 patients with intractable diarrhea and abdominal pain without other cause who had elevated mast cell numbers in intestinal biopsies and responded to therapy directed at mast cells. The patients generally met criteria for diarrhea predominant irritable bowel syndrome (IBS). Normal subjects had much lower levels of mast cells of an average of 12 per HPF.
Until recently this condition was missed due to lack of ability to see mast cells on biopsies in the background of normal cells. However, commercially available special stains utilizing immunohistochemistry for the enzyme tryptase allows the mucosal mast cells to be seen and counted in intestinal tissue obtained from routine random intestinal biopsies.
Over the past year I have been asking the pathologists to perform mast cell stains on intestinal biopsies in my GI patients with diarrhea and abdominal pain. Recently, I began expanding this to include as many patients as possible as well as requesting these stains be done on biopsies performed previously in patients who I suspected might have this condition.
I have now accumulated fifty patients meeting criteria for mastocytic enterocolitis or mastocytic enteritis. These patients are in various stages of evaluation and treatment. I am collecting and analyzing the clinical information with the intent to submit the data for publication. What I have observed on initial review is that appears to be a higher than expected prevalence of the celiac disease risk genes DQ2 and DQ8. In particular, DQ8 appears to be overrepresented compared with the incidence in the general population. There also appears to be an association with celiac disease, non-celiac gluten sensitivity and multiple food intolerance.
The latter finding of multiple food intolerance determined by mediator release testing abnormalities (MRT, Signet Diagnostic Corporation www.nowleap.com; Alcat www.alcat.com) makes sense. The principle of these tests is the detection of changes in cell volumes that occur due to chemical mediator release from cells present in the blood. The tests are not specific for the mediator or mediators released but is assumed that the greater the reaction the greater the number of mediators released and more likely a particular food, chemical or food additive can cause an adverse reaction.
The laboratories that provide mediator release testing report great success in treating a variety of symptoms commonly attributed to food intolerance or chemical/additive sensitivity. It is my belief that mast cells are heavily involved in this process. This would make sense since success with conditions now being associated with mast cells are reported to respond favorably to dietary elimination of foods or substances with abnormal MRT reactions. Classic examples include IBS, headaches, and interstitial cystitis that have been linked to mast cells as well as stress that is now linked to increase mast cells and mast cell degranulation releasing mediators.
Mediator release tests are criticized by some U.S. doctors, in particular www.quackwatch.com as being unproven or not proven for "food allergy” evaluation. However, they are not food allergy tests. Food allergy is an IgE mediated type I immediate immune response known as allergy. MRT tests for non-immune delayed type reactions resulting from mediator release from immune cells. The point is that MRT is not food allergy testing it is a form of non-immune food intolerance or sensitivity reaction.
New articles published in the January 2008 issue of the journal Gut reveal exciting new associations of mast cell degranulation with postoperative ileus and a link to a stress hormone. The first study may be the first to show that mast cells in human bowel release mediators when the bowel is handled during surgery resulting in temporary bowel paralysis known as postoperative ileus. The minimally invasive surgery technique of laparoscopy results in less mechanical stimuli to the bowel and has a lower incidence of postoperative ileus.
Stress association with IBS and inflammatory bowel diseases (Ulcerative colitis, Crohn's disease) has been long known but a mechanism had not been determined definitely. In the same issue of Gut investigators showed that the stress hormone corticotropin-releasing hormone (CRH) regulates intestinal permeability (leaky gut) through mast cells. The investigators even identified specific receptors on mast cells. This new information sheds new light on the possible link of leaky gut and mast cells with IBS, IBD and celiac disease.
So, how do I believe this new information may help us? Since stress can increase mast cells in the bowel and these cells can release mediators that cause gut injury and symptoms, stress reduction important. These cells can cause abdominal pain, diarrhea, and constipation as well as other symptoms outside the gut so they are important. Yet, the significance of these cells is generally not recognized because most doctors, including gastroenterologists and pathologists are unaware of their presence and importance.
These cells cannot be seen in the intestine without special stains done on intestinal tissue obtained during upper endoscopy or colonoscopy. Those stains are not routinely done but generally require the doctor performing the biopsy to request them. If no biopsy is performed then obviously these cells cannot be found. There may be a genetic predisposition for what I think may be better termed mastocytic inflammatory bowel disease (MIBD) rather than mastocytic enterocolitis. There also may be the same genetically determined white blood cell protein patterns that are associated with Celiac disease playing an important role in MIBD.
As note above, stress reduction and probiotic therapy may be helpful to reduce mast cells and leaky gut but what about once the mast cells are increased in the gut. Once elevated mast cells are present, treatment may include medications and dietary interventions. Antihistamines, both type I (e.g. Claritin, Allegra, Zirtec) and type II (e.g. Zantac, Tagamet, Pepcid) to block histamine effects have been used successful in reducing abdominal pain and diarrhea in people with mastocytic enterocolitis. A very specific mast cell stabilizer, sodium Cromalyn (Gastrocrom), also has reduced symptoms. It is an accepted therapy for the more severe condition of generalized mastocytosis.
Searching for food allergies and food intolerance (by mediator release testing) followed by dietary elimination of problem foods until leaky gut resolves and mast cell numbers in the bowel reduce is also helpful in my experience. Food allergy testing consists of skin testing and IgE RAST antibody tests. These tests do not exclude non-allergic food intolerance and sensitivity. Antibody tests for IgG in blood or IgA in stool or saliva have been used for food sensitivity. In my experience MRT tests are much more helpful as they look for any abnormal mediator release to a variety foods, chemicals, or additives, regardless of the nature.
Stay tuned for new developments about the role of mast cells and look for more interest in mastocytic enterocolitis in the future. I propose that the GI community should adopt the broader term mastocytic inflammatory bowel disease since there is information indicating mast cells have an important role in allergic esophagus and stomach problems.
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 Mastocytosis information
The Mastocytosis Society
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Dr. Scot Michael Lewey
“Dr. Celiac, the food doc”
1699 Medical Center Point
Colorado Springs CO 80907