Saturday, February 23, 2008

What are mast cells and why should I be interested? More on mastocytic enterocolitis and a link to refractory Celiac disease.

Why should you be interested in mast cells?

Do you have unexplained or poorly controlled symptoms? Do you have severe allergies and/or suspected food intolerance or sensitivity resulting in various health problems. Are your health problems difficult to shake, reverse, or are they being blamed on poorly understood diseases? Have you been told you have irritable bowel syndrome (IBS) but have had little improvement with the treatments offered or recommended to you?

Then you should be interested in learning more about mast cells. A mast cell problem might very well be the cause. They are, at least, likely to be contributing to your feeling ill. They are known to cause severe allergies, unexplained or difficult to treat symptoms effecting numerous parts of the body. The good news is that there are several effective treatments available for mast cell conditions. However, a mast cell problem needs to be suspected before it can be confirmed.

What are mast cells?

Mast cells are unique immune cells that have granules containing various chemical mediators that have many important bodily functions. We have mast cells distributed all throughout our body. These unique cells control many bodily functions and are important immune, allergy and infection fighting or defensive cells. They commonly reside at our body's various borders where we are exposed or vulnerable to attack. However, if we have too many of these covert immune cells in an area or they misbehave, severe symptoms and serious disorders can result.

Why do I care so much about mast cells?

My interest in these cells over the past year had been primarily because they have been suspected for years as a cause of IBS or the symptoms attributed to IBS. In the past year or so special stains have become available to look for these cells in intestinal biopsies. In just the past few months numerous new research findings have strengthened the link of mast cells to stress, leaky gut and various digestive conditions, especially IBS. However, my interest is not only more intense but is now not just professional. It is personal. I recently confirmed that my wife, who has celiac disease but has continued to have some unexplained or poorly controlled symptoms despite a strict gluten free diet, has exces mast cells in intestinal biopsies done by one of my partners on her about a year ago. This was found after having her previous biopsies evaluated further with special stains for mast cells. I think these excess cells are probably to blame for her apparent refractory celiac disease symptoms and ongoing non-digestive symptoms.

What has been my professional experience with mast cells as a stomach and intestine specialist?

In just over a year I have found over 60 patients who have excess mast cells in their intestinal lining that could only be detected when MCT stains were specifically requested. Almost all of these people would otherwise been told their biopsies were “normal” or non-diagnostic. This includes several of my celiac disease patients on a strict gluten free diet (GFD), usually with “normal biopsies” and blood tests who have continued to have problems. Though most celiac disease patients dramatically respond to a gluten free diet, some continue to have problems. What I have found is that some of these people have increased mast cells in their biopsies. They meet diagnostic criteria for new condition known as mastocytic enterocolitis or what I prefer to call mastocytic inflammatory bowel disease (MIBD).

Why are they called mast cells and what is so unusual about them?

Mast cells have been known about since at least 1878. A German scientist Paul Ehrlich first described them but he mistakenly thought that since they contained granules that their function was to nourish tissues. This mistake is understandable since mast cells are commonly found near blood vessels and nerves. His name for them was derived from “Mastzellen”, a German term for “feeding-cells”. It is now known that these granules contain various chemical mediators important for the role of mast cells in immune and nerve regulating functions.

Why are mast cells granules and chemical mediator release so important?

Full of chemical mediators that are released when their abundant granules “degranulate”, mast cells have a great many effects on the tissue were they reside. Mast cells can be triggered to degranulate, thereby releasing their chemical mediators, in response to mechanical stimulation, stress, and other immune or nerve signals. Mast cells originate in the bone marrow. They then travel via the blood stream and lymph to tissues where they specialize. Their tissue specific specialties depend on their location and functions needed at that tissue location.

Where are mast cells and can they be missed?

Being widely distributed throughout the body, tissue specific mast cells are typically found near blood vessels and nerves though they are hard to see under the microscope without special stains. They are covert. Giemsa, Toludine Blue and special immunohistochemistry stains for tryptase are stains that are used to help see mast cells. However, they are not routinely used. Mast cell tryptase (MCT) stains take of advantage of the large amounts of tryptase in the granules. Giemsa and Toludine Blue stains don't allow mast cells to be seen well if they have released their chemicals from their granules. Mast cell tryptase is specific for these cells and allow them to be seen even if they have degranulated. It may also stain tryptase that has been released into the tissues.

Since, these stains are not routinely ordered or done on tissue biopsies, increased mast cells is frequently missed. This is a particularly important point in the intestine. Only recently has it been recognized that increased mast cells may be present in intestinal biopsies of people with IBS, especially when abdominal pain is severe and diarrhea is present. However, constipation can occur with increased mast cells. An example of increased mast cells in a biopsy of intestinal tissue is shown below. The mast cells are easily seen with the tryptase stain as brownish cells mixed within the tissue.

In this example of mastocytic enterocolitis in one of my patients and kindly provided as courtesy to me from GI Pathology PLLC, it is clear that there are increased mast cells. You can easily count more than 20 per high power field of view under the microscope and make the diagnosis. However, if the special stain had not been used this finding would be completely missed.

Have you had intestinal biopsies that you were told were normal? If so, you should discuss with your doctor having those biopsies stained with mast cell tryptase immunohistochemical special stains to look for excess mast cells. This usually can be done on biopsy tissue that is still available at the pathology laboratory where your samples sent to be reviewed by a pathologist. Most laboratories retain samples for up to five years, some even longer. If the laboratory cannot do the special stains you can request that samples be sent ot GI Pathology in Memphis TN ( Lets explore more about mast cells in the next post and I will take up my review of leaky gut again in future posts as well.

Copyright © 2008, The Food Doc, LLC, All Rights Reserved.

Scot M. Lewey, D.O., FACP, FAAP, FACOP
Gastroenterology Associates of Colorado Springs
1699 Medical Center Point
Colorado Springs CO 80907
719 387 2110 Fax: 719 302 6000

Author Bio

Dr. Scot Lewey is a digestive disease specialist doctor (board certified gastroenterologist) whose medical practice focuses on digestive and food related illness. Also, known as Dr. Celiac, the Food Doc, Dr. Lewey shares his experiential knowledge for a healthy gut, healthy life on-line. Start learning today from his extensive personal and professional experience. Dr. Lewey is uniquely qualified as an expert and one of the few GI doctors who is also gluten sensitive and dairy sensitive. He has nearly a quarter of century of experience in the diagnosis and treatment of food allergy & intolerance, colitis, Crohn's disease and IBS. He is married to someone who has Celiac disease. He and his family live gluten free in Colorado.

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Anonymous said...

What are the symptoms that can still exist even after eliminating gluten? What are the most common types of food or food chemicals that irritate the mast cell besides gluten?

glutengirl said...

Well, there's nothing like a Sunday morning epiphany to brighten up your day! A full two years into my gluten-free lifestyle after a biopsy-confirmed diagnosis of celiac disease, my chronic anemia is a thing of the past, but my intestinal "issues" continue unabated. My gastro guy and my primary care physician have thrown up their hands and suggested that I just learn to live with the incessant diarrhea. I haven't accepted that answer, and your post on mast cells, gives me a new direction to explore. Thanks for your research.

allergic2itall said...

Will a tryptase blood test rule Mast disease out? I was told so, but find it hard to belive. I think if so one should be blood tested only when you are having an episode. Many gastro's if they now will consider Mast disease will perform the blood test first and if it is negative not continue with the internal tryptase smear. Please keep this up, I am into years of avoiding everything,make every food I eat, never eating out and still not doing well and have just about given up on doctors.
Mrs high eosinophills and allergic 2 it all, but all the other tests are normal :)

Anonymous said...

is there a link with mast cell and pms symptoms? I am noticing worsening pms symptoms since my diagnosis of mast cell entercolitis.

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