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 PHYSICIAN'S MANUAL

Montana Celiac Society

Compiled & Designed by Donald & R. Jean Powell/2001

2nd Edition, 2003; 3d Edition, 2004; Web Edition 2005

 PHYSICIANS'

MANUAL

Contains Articles presented by Physicians For Physicians & Patients,

describing Celiac Disease and Dermatitis Herpetiformis.

A Manual for Physicians

Presentations By:

Gastroenterologists, Pediatricians, Neurologists, Dermatologists, Dental & Gastroenterological Researchers, each with long-standing Celiac experience.

Foreword

  The following manual is comprised of articles written by physicians and other professionals that have been published from Celiac journals, the internet, videos and periodicals.  Montana Celiac Society reproduces them here for the benefit of physicians who may have questions regarding Celiac patients.

While Dermatitis Herpetiformis articles are in a category separate from articles describing Celiac Disease, DH patients are technically and medically Celiac patients, requiring the same diet and suffering from the same villi involvement.  The diet is imperative for them as well.

Montana Celiac Society is a non-profit corporation that was founded by a small group of Montanans diagnosed with Celiac Disease in the early 1990's.  Each patient was informed at that time that the ratio of the disorder was 1:10,000.  Serological screening in the United States has, in the 12 years since, proved a demographic among Northern European Caucasian descendents in the US to be 1 in approximately 120.  This is true in Montana.

The subscription list of the MCS newsletter Gluten-Free Friends has grown in Montana from the original 7 members in 1990 to over 715 subscribers in 2005, including subscribers from over 30 states.  As diagnosis improves, numbers grow exponentially.

FOLLOWING IS THE LIST OF MCS OFFICERS AND DIRECTORS 4/2005:

DIRECTORS:

Judy Cass, Director

Tim Harris, Director

Pauline Lucas, Director

Frank Murphy, Director

Executive Director, Founding President: R. Jean Powell

OFFICERS:

President/Financial Manager: Dorothea Caluori

Vice-President: Denise McGough

Secretary: Judy Harris  

Patron: Marlys Werle

Periodical Resources: Houston Celiac Support Group, Janet Rinehart, Ed.; Tri-County CS Support Group, Jim Lyles, Ed.; Alamo Celiac, Lynn Rainwater, Ed.; CSA/USA Lifeline, Leon Rottman, Ed.; Montana Celiac Society, Gluten-Free Friends, R. Jean Powell, Ed.  Revisions, March 2004; September 2004; May 2005.

  Contents

  1.  Medical Descriptions of Celiac Disease

Celiac Disease & Gluten Sensitivity: by Carol Semrad, Gastroenterologist

Presentation; Questions & Answers: by Alessio Fasano, MD

The Spectrum of Celiac Disease: by Joseph Murray, MD

Celiac Sprue Research Update: by Kenneth Fine, MD

  2.  Dermatitis Herpetiformis

What is Dermatitis Herpetiformis?: CSA/USA

Dermatitis Herpetiformis: P. Brian Rogers, MD, PS

Dermatitis Herpetiformis: by Joseph Murray, MD

  3.   Associated Disorders

Diagnosis in the 21st Century: by Kenneth Fine, MD

Down's Syndrome: by Lloyd Rosenvold, MD

Schizophrenia: by Lloyd Rosenvold, MD

  4.  Reproductive Disorders

Infertility: by Lloyd Rosenvold, MD

Celiac Sprue & Pregnancy: by Gainer & Phillips, Journal of Perinatal & Neonatal Nursing

     5.  Pediatrics

Pediatric Presentations: by Alessio Fasano, Pediatrics Gastroenterologist

If You're Considering Pregnancy: by Joseph Murray, MD

   6.  Neurological Abstracts

Cerebellar Atrophy & Patchy Demyelinization: by Jerry S. Trier, MD

Epilepsy, Cerebral Calcifications, & CD: Lancet: by William Dickey

Neurological Manifestations of Adult CD: Lancet: by Beversdorf, et al.

Cryptic Gluten Sensitivity: Lancet: Hadjivassillou, et al.

Cerebellum in Cognitive Function: Discover Magazine, 11/96

Autistic-like Tendencies in a Celiac child: Tamala Powell, Anthropologist

  7. Dental Defects 

Associated with CD: Finnish Study, 1988, Dr. Lissa Aine  

    8. Celiac Disease is the 21st Century

by Dr. Joseph Murray, Mayo Clinic, Rochester, Minnesota

  Appendix A:  Blood Screening

  Large Serological Screening Study ; Fasano/Horvath, Montana Statistics

  Appendix B:  Symptoms

Signs & Symptoms of Celiac Disease. CSA/USA

Deficiency Syndromes: Montana Celiac Society

  Appendix C:  Testing

The correct procedure used to test for Celiac Disease; MCS, R. Jean Powell

********************************************************************************

1. Medical Descriptions

Celiac Disease & Gluten Sensitivity

by Carol E. Semrad, MD

Also referred to as celiac sprue, CD is an inflammatory condition of the small intestine precipitated by the ingestion of wheat in individuals with certain genetic makeups. The onset of illness most commonly occurs around age two, after wheat has been introduced into the diet, and in early adult life [third and fourth decades]. However celiac disease can begin anytime in life. In susceptible individuals, the wheat protein gluten triggers an inflammatory reaction in the small bowel that results in a decrease in the amount of surface area available for nutrient and fluid and electrolyte absorption. The extent of loss of intestinal absorptive surface area generally dictates whether an individual with celiac disease will develop symptoms.

Individuals with celiac disease may experience severe symptoms such as diarrhea, weakness, and weight loss indicating a marked decrease in intestinal absorptive surface area involving much of the small intestine. On the other hand, some individuals present with anemia related fatigue and have no symptoms referable to the gastrointestinal tract. Such individuals likely have disease limited to the proximal small bowel where iron is normally absorbed, the remainder of bowel adequate for nutrient and fluid absorption. Other extraintestinal manifestations of celiac disease include osteopenic bone disease, tetany, and rarely neurologic disorders.

Gluten sensitivity can also manifest itself as a blistering, burning, itchy rash on the extensor surfaces of the body [dermatitis herpetiformis]. Most of these individuals have intestinal biopsies characteristic of celiac regardless of gastrointestinal symptomatology. Recently, with the discovery of antibodies which are specific for celiac disease, screening of families of celiacs and select populations have identified a growing number of asymptomatic individuals who have circulating antibodies and changes on intestinal biopsies characteristic of C.D.

These individuals clearly have a gluten sensitivity but it is unclear if they will develop the clinical features of celiac disease over time.

Removal of wheat [gluten] from the diet of individuals with celiac disease or gluten sensitivity results in regeneration of the intestinal mucosal absorptive surface area and resolution of symptoms in most patients.

There are two important factors that contribute to the development of celiac disease:

1. The ingestion of wheat:

The "Coeliac Affectation" was first reported by Gee in 1888. However it was not until 1950 that wheat was proposed to be the cause of celiac disease. The evidence was based on the observation of a Dutch physician named Dicke who noted during World War II, a time when wheat grains were scarce in Holland, that children with celiac disease who had otherwise failed to thrive, improved on a wheat-poor diet. Since then the large water-insoluble protein, gluten, present in wheat has been identified as the offending substance. Extraction of gluten with alcohol has further narrowed activity to smaller proline-rich proteins called gliadins, which are capable of precipitating disease in previously asymptomatic celiacs. Analogous proteins exist in other grains such as rye, barley, and oats. These grains are also capable of exacerbating celiac disease. The specific peptide sequence of the gliadin responsible for triggering intestinal inflammation has not yet been identified.

2. The Genetic Background of the Individual:

Celiac disease runs in families. First-degree relatives of individuals with celiac disease may or may not manifest symptoms of the disease. Predisposition to gluten sensitivity has been mapped to the major histocompatibility [MHC] D region on chromosome 6. The most important HLA haplotype is Dqw2, which is often in linkage with DR3. Other important HLA haplotypes identified are DR7 and DPB 1, 3, 4.1 and 4.2. The sites on these MHC class 2 expressed proteins responsible for interacting with gliadin and host T cell receptors thereby sensitizing the intestine to gluten have not been identified.

The main function of the small intestine is to absorb nutrients and fluid and electrolytes, a process depending on adequate surface area. In this regard, the absorptive epithelium [villus] of the small intestine is pleated in the intestinal lumen to increase its surface area. Intestinal inflammation of any etiology, if severe enough, is associated with flattening of the villus epithelium, which results in a decrease in intestinal absorptive surface area. How activated inflammatory cells in the lamina propria beneath the surface epithelium and intersperse between epithelial cells bring about villus flattening remain a mystery. Intestinal biopsies taken from individuals with celiac disease and gluten sensitivity show a spectrum of these mucosal abnormalities. Three distinct patterns have clinical relevance.

Infiltration of the villus epithelium with lymphocytes and a normal villus and crypt architecture.

This pattern is found in 40% of individuals with Dermatitis Herpetiformis and a portion of first-degree relatives of celiacs who have no gastrointestinal symptomatology.

A flat mucosa characterized by villus flattening & crypt elongation with inflammatory cells in the lamina propria.

This pattern is classically found in individuals with celiac disease who have gastrointestinal symptoms, but has also been reported in asymptomatic celiac relatives and individuals with Dermatitis Herpetiformis. It is important to keep in mind that intestinal biopsies are most commonly obtained endoscopically from the duodenum and therefore do not provide information as to the extent of disease along the length of jejunum. Since the duodenum is the first segment of small intestine exposed to gluten, villus flattening might be most severe in this location while much of the jejunal villi remain relatively normal, accounting for an asymptomatic state. In most of these individuals, treatment with a gluten-free diet results in the return of villus and crypt architecture to normal or near normal.

A hypoplastic mucosa characterized by villus flattening and small crypts.

This biopsy is found in the small group of patients with presumed severe celiac disease refractory to a gluten-free diet. These individuals have persistent ill-health due to intestinal malabsorption and sometimes require nutritional support parenterally. This intestinal lesion is irreversible.

There is no test yet which is definitively diagnostic of celiac disease. Relief of symptoms or reversion of an abnormal intestinal biopsy to normal on a gluten-free diet is the most convincing evidence that an individual has celiac disease or gluten sensitivity. Intestinal biopsies as discussed above show characteristic findings compatible with celiac disease but are obtained just as often to exclude other intestinal conditions, most importantly infection, which can have a clinical presentation similar to celiac disease.

The first serological marker reported to be of use in the diagnosis of celiac disease was the IgG class antigliadin antibody [AGA]. Though sensitive, this antibody is also found in other diseases and is therefore not specific for celiac disease. IgA class AGA is more specific; however about 2% of patients with celiac disease have selective IgA deficiency. A positive IgG and IgA AGA gives a reported sensitivity of 96% to 100% and specificity of 96% to 97%. If only the IgG AGA is positive an evaluation for selective IgA deficiency should be undertaken. Antireticulin antibodies [ARA] have also been reported in individuals with celiac disease, but are non-specific. IgG ARA is relatively useless, but IgA ARA has a high sensitivity and specificity in adults [97% and 98% respectively]. In children these values are much lower. Recently two antibodies, IgA class antiendomysial antibody [EMA] and human jejunal antibody [JAB], have been identified which are highly sensitive and specific for active celiac disease [100% sensitivity and specifically reported in one study.] The one best characterized is the EMA, an antibody against endomysium reticulin fibers. In adult studies, EMA was only found in patients with active celiac disease and not other diseases.

The test is less powerful in children as  EMAs have been detected in other childhood diseases. The more important limitation of  EMAs in children is the reported fall in sensitivity observed in children with celiac disease less than 2 years old. Even the EMA and JAB antibody tests in adults are not foolproof as they may not be positive in individuals with celiac disease and IgA deficiency.

A panel of these antibodies seems to be most useful in the diagnosis of celiacs. A combination of IgG AGA, IgA AGA, and EMA have a reported positive predictive value of 99.3% when all were positive and a negative predictive value of 99.6% when all were negative. These antibodies tend to lessen or disappear when individuals are maintained on a gluten-free diet. Antibody testing is important in screening individuals who are at risk for having celiac disease but have no symptomatology, in individuals with atypical symptoms or extraintestinal manifestations of celiac disease, and in individuals with presumed celiac disease who fail to respond to a gluten-free diet. Patients with positive antibody tests must undergo small intestinal biopsy to confirm the diagnosis and assess the degree of mucosal involvement.

Unlike autoimmune diseases in which the precipitating antigen either is not identified or if identified cannot be removed, the antigen precipitating celiac disease, i.e. gluten, can be removed from the diet. This sounds easier than done as wheat is used as a filler and thickener in a number of store bought and restaurant prepared foods. Avoidance of gluten in the diet requires careful scrutiny of food labels for the presence of wheat and other offending grains such as rye, oats, and barley. Products labeled wheat-free are not necessarily gluten-free. Common foods that cannot be eaten include breads, bagels, pastries, pasta and pizza. There are companies throughout the United States that produce gluten-free products made predominately from rice flour. Most patients treated with a gluten-free diet will notice a lessening of symptoms within 2 weeks and no follow-up intestinal biopsy is required. A small group of patients have partial or no response to a gluten-free diet.

One important cause of a poor dietary response is the continued ingestion of gluten in foods thought to be gluten-free or just plain dietary cheating.

Antibody testing while such patients are on a "strict" gluten-free diet may be useful in this situation. A kit that utilizes the Elisa assay has been developed to test food products for the presence of the gluten antigen.

In individuals who have a poor response to a gluten-free diet, a repeat intestinal biopsy is mandatory after 3 months treatment to assure that other intestinal lesions such as infection or intestinal lymphoma were not missed.

In symptomatic patients the obvious answer is to relieve debilitating symptoms. What about individuals who have minimal symptoms or who are asymptomatic? There are two reasons to treat such individuals with a gluten-free diet: 1) a subgroup of these patients will progress to more severe disease and hence develop symptoms and 2) there is an increased incidence of small intestinal lymphomas and adenocarcinomas in individuals with celiac disease. The increased incidence of cancer seems to correlate with the degree of intestinal inflammation [activity] present, as individuals whose disease responded to a gluten-free diet and who remained compliant with the diet had a lower incidence of such cancers. Whether individuals who are found to have elevated antibodies specific for celiac disease but are asymptomatic and have normal intestinal biopsies should be treated with a gluten-free diet is unclear.  CAROL SEMRAD, M.D.  semrad@columbia.edu/©1995 CU Div. of Gastroenterology

From the video of the Dr. Alessio Fasano Presentation held June 19th, 1999 at Billings Deaconess Hospital, Billings, Montana.

Dr. Alessio Fasano is Professor of Pediatrics and Director of the Department of Pediatric Gastroenterology & Nutrition, University of Maryland School of Medicine. Internationally, he is considered one of the foremost Celiac researchers in the field.

THREE POINTS:

1)  It’s Permanent: It doesn't go away.  

                2) Genetic Factors: We are genetically   predisposed.

                3)  Environmental Factors:  You must be consuming a diet that includes gluten/gliadins.

 

Genetic Predisposition:  Familial Occurrence:  a. 2 to 4% in general population--10% in first degree relatives. b. 70 % of monozygotal (one egg or identical) twins. c. H(human)  L(leukocyte)  A(antigen) =  HLA fingerprints:  70-80% of Celiacs have positive HLA.

Why is HLA important?   There are receptors on the cells of the intestine, on the enterocytes, which recognize gluten, bring it to the other side of the mucosa (lining), triggering an immune response which activates lymphocytes, producing tissue damage.

                Environment:  Gliadin:  Gliadin is a prolamin, an alcohol-soluble fraction in cereal grains. 

                Adenovirus 12:  There may be a theoretical infectious factor.  Up to 85% of Celiacs test positive for Adenovirus 12 but less than 10% of general population test positive.  It is still an open issue.

Prevalence:  There is data from Europe, but none from the U.S.  When we looked at Malmo, Sweden, and Copenhagen, Denmark---20 miles apart--- we saw that in Malmo the incidence was 1:500 but in Copenhagen it was 1:11,000, which has been also claimed in U.S.! (as confirmed by biopsy).  If we look for typical presentation we will miss most of it.  A decline was claimed in the mid-eighties because babies were being breast-fed & introduction of gluten was late, which made the reason (for the so-called decline) unclear. By delaying the onset of the disease the typical presentation became atypical so that the typical guidelines used brought on a major disaster!  Guidelines had to be changed.

Presentation:  It is not uniform, and may be typical or atypical.  Asymptomatic patients may have latent symptoms which will develop later.  The typical (pediatric) patient is 6 to 18 months old, and has symptoms of:  diarrhea, steatorrhea (fatty stools), poor weight gain, irritability, anorexia;  which equal the Celiac Crisis.  We no longer see these (so-called) typical cases (showing a picture of an emaciated baby). .  The classical typical form is just the tip of the iceberg--- showing 1:2500.  But when looking for all forms including symptomatic atypical Celiac Disease the incidence was 1:300! 

Other Organs:  The mouth, with Stomatitis (inflammation of the mouth as in ulcers or thrush); the kidneys, with nephropathy (any disease or damage to the kidney); the joints, with arthritis; the skin, with Dermatitis Herpetiformis (DH); all can be related to Celiac Sprue.  It is universally accepted that DH = Celiac Disease, even though they may have no intestinal complaints.  A biopsy will show typical damage.  Dermatologists here (U.S.) said NO, until skin biopsies showed deposits of immuno-complex with gliadin and gliadin antibodies present in typical lesions of the skin.   All over the world, this is no longer an issue---except in the U.S.  I don’t know why.

Atypical: Short Stature:  20% of idiopathic short stature in Europe is due to Celiac Disease.  At the University of Maryland serum bank there were kids who did and didn’t respond to growth hormones.  We analyzed these samples for IgG antigliadin antibodies.  The kids who responded to growth hormone had normal antibody levels---some of those who didn’t respond to growth hormone had high levels of anti-gliadin antibodies, and all who agreed to the biopsy were found to have Celiac disease.  Another example of misdiagnosis..  Now children with short stature are screened for Celiac Disease with routine lab work.                                           

Enamel Dysplasia:  This discoloration is due to gliadin and gliadin antibodies on the matrix of the teeth.  You can see the damage lines on the matrix of the teeth when gluten was introduced, then withdrawn, and reintroduced. 

Seizures:  Described to be frequently associated with Celiac Disease, due to intercranial calcification, particularly in the posterior of the brain, causing seizures.  We had a four year old girl with recurrent seizures who did not respond to anti-epileptic drugs and was brought to our office because of weight loss.  She had had seizures for 2 years.  She tested positive for the anti-gliadin and anti-endomysial antibodies. The biopsy showed her to be Celiac, and for the first time her seizures were controlled.  Folic Acid deficiency secondarily causes the calcification.  Rarely does the calcium deposit almost disappear, but it did in this case.

Other Immune Disorders:  Diabetes Mellitus, where the genes are on the same chromosome as CD;   the rate is much higher than in the general population; thyroid disease; Sjogren’s syndrome; Rheumatoid Arthritis, collagen vascular disease, and liver disease (this list is from the GIG article describing Dr. Fasano’s lecture).

Mood Changes:  Children come in crazy, screaming, yelling.   A molecule seems to be involved in the internal control of subjects, and gliadin changes behavior by interfering with the inter-active receptors of endorphins. Endorphins are able to change the activity and alert(ness) of people.  We calculated that there are 23,000 receptors per cell, in which alpha-gliadin could cause abnormal interaction.

 Asymptomatic Celiac Disease:  The person is healthy, with no symptoms, but has the typical intestinal histology.  10% of Celiac relatives have intestinal damage, and it is crucial that they be treated as Celiac!

What was the difference between Malmo and Copenhagen?  It was in the screening in Denmark.  Where once they claimed to have the same incidence as the United States, they now have the same as the rest of Europe: 1:300!  The difference is that the clinical presentation is absolutely different.

How do you make the diagnosis of Celiac Disease?  

In European Pediatrics it once was with 3 biopsies:  1. Symptoms on a normal diet---Biopsy showing tissue damage.  2.  Gluten-free diet for one year free of symptoms---Biopsy  3.  Challenge---Re-expose subject for 3 months or until relapse, then have 3d Biopsy.

This was painful for patients and physicians.  Compliance was very poor, and it was a complicated process.  We asked What can we do to improve this painful process?  The breakthrough was the use of anti-gliadin anti-bodies found in the lab in the early 1980’s.  There has been tremendous improvement of this assay to reach the point now where:

                  IgG sub class:  highly sensitive, not very specific

                   IgA sub class:  not sensitive, but highly specific

                   Anti-endomysial & anti-reticulin antibodies:  Highly sensitive and highly specific

The anti-endomysial antibody test required monkey esophagus.  Since I like monkeys and hate to use them for even a very noble issue, I was glad for the alternative, which is much cheaper:  Human umbilical cord.  We get permission in the delivery room.  It is cheap, very specific, and very sensitive.

If Anti-gliadin and Anti-endomysial Antibodies are positive:  we are 99.6% sure it is Celiac Disease, the Positive Predictive value.  But there still needs to be a biopsy.  The test is highly predictive so it is very useful for diagnosis.  It is a different tool, considering the pain people were going through. Tests on 3000 children showed that the same results were produced with the alternative approach as with the three biopsies.

Policy:  To check antibodies once a year.  If you’re getting high signals then, even though you thought you---or your child--were eating appropriate foods you later on discover this is not the case.  

Serological Screening:  Anti-gliadin and anti-endomysial antibody screening shows a much higher prevalence of the disease than expected before.  On the same European map, the triangles are the same size everywhere.  1:300!  There is a uniformity of incidence.

 Clinical Presentation:  Very few (in Denmark) had typical presentation.  Most had Osteoporosis, DH, Short Stature, whatever is on that list.  Awareness of physicians was pretty low.  When we did the screening again of Malmo and Copenhagen, the prevalence of the disease was exactly like the rest of Europe, solving a mystery for us that’s the same mystery we have in U.S.  How come---having the same genetic background---we have such a difference in the incidence of the prevalence of the disease compared to European countries??  Is this because we are different---or merely indifferent?

Pilot Study:  At the Univ. of Maryland we did a study with 159 kids with atypical symptoms such as 1.Short Stature 2. Poor weight gain  3. abdominal pain.  Some tested positive for antibodies and six kids were diagnosed with CD.  One Grandmother was Celiac, and her two grandchildren tested sky-high for antibodies, but we couldn’t do the biopsies.  Their primary physician said “No Way!”  They were healthy. Their insurance company also said no way, because they are healthy.   But they will be back as future customers!

Why is it so crucial to be Gluten-Free even if asymptomatic?  Here you would teach me.  For years you’ve been unhappy and unhealthy.  In Pediatrics if the diagnosis is not on time there is no catch-up growth.  We as physicians have a tremendous responsibility---kids with Short Stature can recover totally their potential growth.  But if we’re late---too late---they will be short forever and ever, and it will be our responsibility!  It is the same with skeletal disorders---osteoporosis.  Every single person with osteoporosis is a failure of a physician to make a diagnosis.  Infertility is also described to be associated with C.D., and the physician has a strong responsibility.

Consequences of Prolonged Exposure:  I am sure you are aware of the consequences of long-term exposure and the incidence of intestinal lymphoma, which is much higher among Celiacs chronically exposed to Gluten than among the general population.  But with a strict gluten-free diet, after five years the difference is negligible with the general population.

  You cannot have a little bit of Gluten once in awhile! A.F.

Questions & Answers

Q: What is the ratio of men to women with Celiac Disease?

A: Of the 1400 we’ve tested so far, 58% are females; of those who’ve tested positive, the ratio is half and half.

Q: The information that you’re sending back in 3 or 4 weeks—is it acceptable with doctors? Will Montana physicians be able to understand what we’re dealing with?

A: Your coordinator will be the connection between the physician and us. If the results are an indication that you need to go to the biopsy and the physician is unsure--for instance if there are no symptoms--he/she may fear that the HMO will never approve to do this.

If this is the case--if the HMO  WON’T agree to the test, we will pay for the procedure. This is one way we invest our money. But if you have  SYMPTOMS, test POSITIVE, and the HMO refuses still, the lawyer comes into the picture!

We would like to review the slides of your biopsy in a blind study. We want to be involved, to help your Internist/Gastroenterologist through this journey if there are such difficulties. If you have a Medical Advisor, then he or she can take the lead and talk with colleagues. We want to facilitate this story as much as we can, either economically or conceptually.

Q: Is there a list of the labs that you use?

A: I use mine. There are 5 or 6 labs total that can do this test. The antiendomysial test is a subjective one (done by a person, not mechanically). The lab person doing the test who does three a year has a different level of experience than the lab person doing it 50 times a day. We have a tremendous volume. On both a clinical and a research basis, every single time that we have found the antiendomysium to be positive, we’ve found the biopsy to be pathological. That means that we’ve found our quality to be very high.

Q: I can think of no one in my family who has a related auto-immune disorder such as lupus or diabetes. Is that something I still need to be concerned about?

A: Not necessarily. It is not a given. For every Celiac to have an auto-immune disorder would be a disaster.

Q: Have you noticed a correlation between non-compliance with the  GF diet and autoimmune disorders being more prevalent?

A: Yes! Stick with your diet!

Q: After you stop eating gluten, how long before symptoms subside?

A: Good question. Our experience is based on how long you’ve been exposed. For kids it may be just a few days; but if you’ve been exposed for years and years, it is sometimes 4 to 6 months.

Q: Is there a connection between Celiac Disease and Multiple Sclerosis?

A: There is no clear association. There are some anecdotal reports, but again we’re talking about two autoimmune diseases. We can’t conclude that there is such a strong association at this stage—the numbers aren’t there.

Q: I’ve been on the celiac diet for 15 years and have never been tested—blood-wise or biopsy-wise. Would you recommend going back to have that done?

A: If you have been so-o-o-o good to be on a gluten-free diet for 15 years, I would not recommend that you make any kind of changes, because you may eventually taste things that you’ve forgotten! Seriously, you’ve shown to yourself a high level of commitment—you’re convinced. On the other hand if you discover you’re not really celiac, you might be very upset!!!

Q: About the gluten challenge: my four-year-old has been on a GF diet for about a year now, and it is extremely obvious that he gets sick if he eats anything with wheat in it. He has not had a biopsy.

A: Again, I think you’re in the kind of situation in which you are extremely convinced and committed to the disease. Believe it or not, you are in a very lucky situation, because if you were to do the challenge, as I would strongly recommend, the time needed to do the entire thing would be brief: he would react immediately, the antibodies would go crazy immediately, and you could do the biopsy immediately.

The entire thing could be done in a matter of a couple of weeks. It’s an investment in the future. You have to understand—and this is well demonstrated—your child may react within a few seconds now, but when he is 14 or 15 this is not necessarily going to happen.

I don’t want to scare anybody, but I want to share with you a sad story.

A few months ago a lady came from Philadelphia, 44 years old, with intestinal lymphoma. She, as a child 6 years old, was diagnosed celiac. When she was 10 she was told that she would grow out of it. She exposed herself to gluten and indeed she did not have any relapse of symptoms until she was 42—and her symptom was intestinal lymphoma. She came to me because she has a 6 year old girl who she wanted screened and indeed the daughter happened to be celiac. You can bet the girl will be on a GF diet for the rest of her life!

So—a few weeks of aggravation now, biopsy now, will be a tremendous investment in the future.

Audience member’s comment: If you can put your child through 2 weeks of misery in the summer, then get him diagnosed before school starts, you will avoid the label of ADD. Also, with a biopsy diagnosis, doctors will not be so apt to try to convince him when he is 20 that he’s "not really" a celiac and then encourage him to go off the diet.

Dr. Fasano: That’s true and has been our experience as well…

Q: If I get the biopsy, should I also say that I am looking into the possibility of lymphoma as well?

A: If you’re celiac and you’ve been diagnosed, and put yourself on the GF diet, it’s the same as the general population. The prevalence of lymphoma will go back to normal, absolutely.

Q: I just got this disease within the last 2 years or so and I am 71…

A: You did not get it in the last 2 years.

Q: I’ve always had it then?

A: You’ve always had it. The problem is, while the 4 year old got sick very quickly, the damage expressed itself to someone so young, you took your time! Your immune system was slow-paced; it’s been a continuous experience. But remember, it has an encounter with your genes and your environment. It has been always, always there.

Q: How old do you want children to be before you do the biopsy?

A: I don’t want children to have the biopsy unless there’s some indication that the antibodies are there, there is a family history, and there are symptoms (due to the environmental exposure to gluten). There is no age limit; we do the endoscopy to neo-nates who are having problems…

Audience member’s comment: Montana Celiac Society has been told by parents that there are no pediatrics gastroenterologists or instruments to do the biopsy in Montana, so parents must travel to Seattle or Denver.

Dr. Fasano’s answer: This is surprising to me. If I ever consider going into private practice, I will come here! (Applause!). If you have a choice between going to an adult gastroenterologist here and a child’s gastroenterologist, I would prefer that you go to Seattle to a pediatric gastroenterologist.

In fact, Seattle has the highest prevalence at 30% that has been found in any of the states. The gastroenterologist there is very, very good. Also, I will let my students know that there is no pediatrics’ gastroenterologist in Montana.

Q: My son did have a biopsy, which came back negative. He had the stool test and was malabsorbing; he had the blood test and one of the antibodies was positive, one negative…

A: Which one? It makes a world of difference…

Q: The doctor said if it had been the other one, he wouldn’t have done the biopsy, just assumed he was celiac. About a month after the blood test he put him on a gluten-free diet, and did the biopsy 5 days later.

A: Wait a minute! He was placed on a gluten-free diet  before the biopsy??? Q: Yes.

A: No-no—No, No! I would do two things: you would be more than welcome to send me the results and copies of the slides so I can take a look at them. Sometimes there are subtle changes as the tissue repairs itself, which an experienced pathologist can pick up. I would be more than pleased to take a look at that.

Second, if the biopsy is normal, unfortunately you do not have any other alternative but to go back on the regular diet, do the challenge, the whole nine yards, until the antibodies turn positive again.

Since he’s on a gluten-free diet now, I would test him first to make sure all the antibodies are normal, expose him to gluten, wait either for the symptoms to appear or for six months if he has no symptoms, then redo the blood test. If you see the antibodies elevate then we do another biopsy. Sadly, you’re in LaLa Land right now… Q: I know…

Q: My sister, mother, grandmother and brother have CD. I took the blood test today; but let’s say I don’t have it and I have kids. Can I just carry it over?

A: Absolutely! Suppose you need a combination of 10 genes to have celiac. You may have 8 of the 10 genes, so you will not be celiac—ever. Still, you have 8 genes—the likelihood that you can marry someone who has the other two genes that will mesh and carry it to your child is possible.

Q. For the past week or so, I’ve been gluten-free. Does that skew this test?

A: Yes. There’s a possibility that it does. My suggestion is to go back on the regular diet, get sick and repeat the test.  Alessio Fasano

You may contact Dr. Alessio Fasano at:  The University of Maryland School of Medicine, 22 South Greene Street N5W70, Box 140, Baltimore, Maryland  21201-1595; Phone #: [410] 328-0812; FAX: [410] 328-1072.

    e-mail: afasano@umaryland.edu. 

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 The Spectrum of Celiac Disease

DR. JOSEPH MURRAY, Mayo Clinic, Rochester, Minnesota

From The Sprue-nik Press, Issue Jan/Feb. 1998; Jim Lyles, Editor

There are many different terms that have been used to describe the disease that we generally call celiac disease (CD); only the first of these is preferred:

Gluten Sensitive Enteropathy--this is the most precise definition, as it describes intestinal damage related to the intake of gluten.

Celiac Sprue--sprue implies diarrhea, which many newly-diagnosed celiacs do not have.

Idiopathic Steatorrhea--this means "unexplained foul-smelling, fatty stools". Many celiacs do not have this symptom either, and in any case the cause  is known (damaged villi), so it can hardly be unexplained.

Non-Tropical Sprue—[as distinguished from Tropical Sprue, which responds to antibiotics. RJP, Ed.] Again the implication is that diarrhea is a major symptom, which is not always the case.

A GOOD WORKING DEFINITION OF CD IS:

"A PERMANENT INTOLERANCE TO GLUTEN THAT RESULTS IN DAMAGE TO THE SMALL INTESTINE, WHICH IS REVERSIBLE WITH THE AVOIDANCE OF DIETARY GLUTEN. " Joseph Murray, MD

UNUSUAL SYMPTOMS

Some of the more unusual non-gastrointestinal symptoms of CD include:

Rickets, dental enamel defects, epilepsy with intra-cranial calcification, delayed menarche in teenage girls, arthritis (synovitis), neurologic disorders, mental "fuzziness", and lupus and other connective tissue diseases.

There are also some unusual gastrointestinal symptoms, which include:

Heartburn, gastrointestinal lymphomas and carcinomas (two forms of cancer), abnormal transaminases (liver abnormalities), and unexplained weight loss.

DERMATITIS HERPETIFORMIS

Dr. Murray believes that ALL Dermatitis Herpetiformis [DH] patients also have Celiac Disease and the gluten sensitivity which occurs in the gastrointestinal tract, producing antibodies. In DH, those antibodies are "dumped" under the lining of the skin, where they sit like small land mines for days, months, or years. One day something triggers them (sunlight, iodine in a cleanser, etc.) into bursting forth as the immune system of the skin begins attacking the deposits, forming the blisters. However, the antibodies originate from the intestine when it is exposed to gluten.

VILLI DAMAGE

Both iron and folic acid are absorbed in the  first third of the small intestine, which is often where much of the villi damage occurs in celiacs. Other nutrients can be absorbed further down in the small intestine. This explains why newly-diagnosed celiacs often have unexplained anemia and/or low folic acid levels with no other apparent symptoms.

CHANGES IN CRITERIA

In recent years the "typical" presentation of CD has been changing. CD tends to appear at an older age now. The symptoms are more often atypical instead of the "classic" symptoms of diarrhea, bloating, wasting, and fatty, smelly stools. It is diagnosed more often in adults now than in children. The pediatric age of diagnosis is now 4-7 years, whereas it was much younger in the past. There tends to be less marked growth retardation and fewer deficiencies in newly-diagnosed celiacs, [because of recognition of the early symptoms. Ed.].

THE MANY REASONS

Breast feeding is encouraged today, whereas in the past it was actually discouraged; this means the introduction of gluten to the diet will occur later. Also, the IgA/IgG antibody blood tests often help to "find" celiacs sooner, before damage has become too severe. There is a trend towards more aggressive screening for CD in many countries.

CELIAC DISEASE DIAGNOSIS

The rate in Europe varies from 1:200 (one out of every 200 people) to 1:2,000.

It appears to be rare in Negroid and Asian populations.

The rate of diagnosis in most areas is proportional to the degree of suspicion!

6% of adult Type I diabetics in Iowa have CD.

1:10,000 children in Buffalo, New York have been diagnosed with CD.

1:4,700 Olmsted, Minnesota residents have been diagnosed with CD (from a Mayo Clinic study).

The rate in healthy blood donors in most tested countries varies from 1:100 to 1:300.

Among diagnosed celiacs, the ratio of females to males is 2:1. However, in screening tests the ratio is 1:1. Does this occur because males delay in seeking medical help?

INCREASES IN DIAGNOSES:

At the University of Iowa, the rate of diagnosis has gone up dramatically, perhaps because there is a higher degree of suspicion regarding CD. Prior to 1988, about 2 cases of CD were diagnosed per year at the University of Iowa. In 1991, there were 18.

Currently 55-60 Iowa cases of CD are diagnosed per year!

From 1980-1988 in Iowa,70% of the diagnosed celiacs presented with "classic" celiac symptoms. Since 1992, only about 30% have the classic symptoms at the time of diagnosis. [This suggests that the remaining 70% display the so-called "atypical" symptoms. Because of improved diagnoses, a redefining of terms is essential. rjp, Ed].

OTHER MALADIES

Many celiacs have been diagnosed or misdiagnosed with other maladies prior to their diagnosis of CD, including:

Irritable bowel syndrome (IBS), sometimes a catchall for unexplained GI symptoms

Primary lactose intolerance

Inflammatory bowel disease (IBD)

Psychiatric illness

Pernicious anemia

Menstrual blood loss

Peptic ulcer disease

Diabetic diarrhea

Chronic fatigue syndrome

Giardia

Pancreatitis/SOD dysfunction

Fibromyalgia

Fiber deficiency

Multiple Sclerosis

LOOKING AGGRESSIVELY

Dr. Murray believes in aggressively looking for CD:

If you are already doing an endoscopy, then always do a duodenal biopsy. You are "down there" anyway, and it only takes a few more minutes.

Screen all high-risk groups for CD. Along with the "usual" groups, you should look at those with IgA deficiency (which is more common in celiacs) and Caucasians with lactose intolerance.

Look for CD in children with non-specific abdominal pain.

PSYCHOLOGICAL PROBLEMS

Many factors can lead to psychological problems in untreated or undiagnosed celiac patients:

1. Fatigue   2. Feeling Ill   3. Dietary illness  4. Social isolation  5. Vitamin deficiencies   

6. Direct toxic effect of gluten on a leaky gut.

RECOMMENDED FOLLOW-UP

· Ensure a well-balanced gluten-free diet.

· Take vitamins for 100% of the Recommended Daily Allowance [RDA].

· Take Calcium and Magnesium supplements.

· Cholesterol may rise, since malabsorption may have caused it to be unnaturally low.

· Check for lactose intolerance after the villi have healed.

· Check for complications and associated diseases such as bone density problems.

A RECOMMENDED TEXT

Dr. Murray recommends the book Celiac Disease, by Michael Marsh, (Blackwell Scientific Publications, Nov. 1992) to physicians associated with Celiac patients. It thoroughly explains the disease. It's priced at about $175.00, well worth the cost if it helps a physician become more interested and to learn about this misunderstood disease.

Contact Dr. Murray at:  

Dr. Joseph Murray, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905, [507] 284-2631 % Carol

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CELIAC SPRUE RESEARCH UPDATE

by KENNETH FINE, MD

Dr. Fine has been serving the celiac/gluten sensitive community as a clinical researcher, support group advisor and clinician for over 12 years.

I would like to announce the formation of two new public service websites serving the needs of the celiac and gluten sensitive community. The first is a website called FINERHEALTH AND NUTRITION at the address www.finerhealth.com containing a wealth of information on celiac sprue and the closely related syndrome, microscopic colitis. I have made myself available for consultation by phone for anyone feeling they need guidance relating to celiac sprue, microscopic colitis, or for more general preventive health-related issues. Gluten-free dietary consultation with experienced registered dietitians also is offered. Online "chats" take place Sundays through Wednesdays beginning at 8:00 PM US Central time for topics related to celiac sprue. The chat room is available to anyone anytime. There are slide shows of medical information and intestinal biopsy and endoscopy photographs relating to celiac sprue and microscopic colitis, as well as a very large message board.

To help potential celiacs or their family members in need of testing for immunologic reactions to gluten and other dietary sensitivities, I have devised a mechanism for such individuals to be tested by mail without a blood test or intestinal biopsy. The new stool test I have developed is carried out in a specialty laboratory called ENTEROLAB and can determine if an individual is gluten-sensitive and/or is experiencing malabsorption of nutrients and vitamins. Through extensive research, the test has proven to be more sensitive than blood antibody screening for antigliadin and antitissue transglutaminase antibodies, the diagnostic antibodies for this syndrome. The testing can be carried for a cost below that of most commercial laboratories' gluten sensitivity testing panels. At a relatively low cost this test can also be carried out by mail without drawing blood. In this way, all samples can be collected by the individual at home and returned to  EnteroLab by overnight mail. Tests can be ordered at www.enterolab.com

As an extension of the services offered at FinerHealthTM & Nutrition Nutrition & EnteroLabTM, I have founded the INTESTINAL HEALTH INSTITUTE to serve the public directly through medical research, education and awareness. Additional information on the Intestinal Health Institute is located at www.intestinalhealth.org. Proceeds from the consulting and lab testing service are donated to this institute.

Thank you for your interest in  FinerHealth and Nutrition, EnteroLab, and the Intestinal Health Institute. My interest is in helping those who suffer needlessly from gluten and other food sensitivities. Please let me know how I may serve you. You may phone:  [972] 686-6869. Kenneth Fine, MD.

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2. Dermatitis Herpetiformis

What is Dermatitis Herpetiformis?

CSA/USA Brochure

Dermatitis Herpetiformis is a form of gluten-sensitive enteropathy in which the skin is the major organ involved, with skin manifestations usually the most prominent. Red raised patches of skin develop with tiny blisters. These are accompanied with burning and itching. There may be raised swollen areas that appear similar to patches of hives.

The most common areas of occurrence are the elbows and knees, along with the buttocks, the shoulder blades, and face involved, with the eruptions frequently appearing symmetrically. Eruptions can also occur in the mouth, but are not as common. The severity of the symptoms varies and can wax and wane when untreated. It can appear at any time after wheat, rye, or barley, are added to the diet, but occurs more often after the teen years.

It has been generally recognized that all patients with DH show similar intestinal damage, although often less severe, as those seen in  Celiac Disease. There are some medications available for treating the rash, but the medication  [Dapsone] does not heal the damage to the intestinal mucosa. If grains are consumed, damage to the mucosa continues with repeated damage causing the greatest health risk.

CSA/USA: Celiac Sprue Association/US of A, Inc.

Box 31700, Omaha, Nebraska 68131-0700 [402] 558-0600

Dermatitis Herpetiformis

P. Brian Rogers, M.D., PS. Dermatology & Allergy

1727 West College Avenue Bozeman, Montana 59715 [406] 587-4432

DERMATITIS HERPETIFORMIS was first described by Louis  Duhring in 1884. This is a rare blistering disease of the skin with an unknown prevalence. It is very rare in blacks and almost unheard of in Japanese people. The peak incidence of DH is in the 2nd, 3rd, and 4th decades of life.

The primary skin lesion in dermatitis herpetiformis is an extremely itchy vesicle or blister. Occasionally hive-like plaques or erythematous papules are also seen. The lesions have symmetrical grouping and often are found over the elbows, knees, shoulders, buttocks, and sacrum. A biopsy of the lesions shows a blister beneath the epidermis with collections of neutrophils [white blood cells] in the upper layers of the dermis. Immunofluorescence shows a granular deposition of IgA ,one of the five types of immunoglobulins normally found in all humans.

Dermatitis herpetiformis is thought to result from a  hyperresponsive immune system. This disease most commonly occurs in a certain genetic type termed  HLA B-8. Other diseases of the immune system sharing this genetic characteristic include celiac sprue, chronic hepatitis, Grave’s disease [hyperthyroidism], diabetes, and systemic lupus erythematous.

Eighty percent of patients with DH have an abnormal flattening of the villi in the small intestine. It is felt that the wheat-related cereal protein, gluten, is responsible for this change in the intestinal villi. An identical gastrointestinal disorder is found in Celiac Disease.

The mainstay of treating dermatitis herpetiformis is a gluten-free diet. It is felt that avoiding gluten also reduces the chance of lymphoma of the small bowel or adenocarcinoma of the small bowel in patients with both DH and celiac sprue. In addition, patients with DH should avoid iodides since the skin lesions may worsen.

In many patients diet alone can control the disease but if medications are needed  Dapson or sulfapyridine are indicated. Dapsone is the more effective of the two and probably works by inhibiting the chemotaxis of neutrophils into the skin. It has numerous side effects such as hemolytic anemia [in people of Mediterranean descent], peripheral neuropathy, liver damage, kidney damage, agranulocytosis, or even psychosis. In the majority of the cases, strict adherence to a gluten-free diet will greatly reduce or eliminate the need for Dapsone or other drugs. Spontaneous remission in this disease is rare, but it has been reported. Brian Rogers, MD.

Dr. Brian Rogers, M.D., P.S., 1727 West College, Bozeman, Montana,  59715 [406] 587-4432

Dermatitis Herpetiformis

by Dr. Joseph Murray, Mayo Clinic, Rochester, Minnesota

DH is an extremely itchy skin rash. Even poison ivy may not come close according to those who have had both. It affects the elbows, knees, buttocks, back of the head, and scalp. (Dr. Murray described one lady who developed lesions in her outer ear canal). Coming in waves, crops of little bumps appear and soon turn into the extremely itchy blisters.

DH is often considered a skin disease, but that is not strictly true. DH is a manifestation of intestinal intolerance to gluten. Research has been done in which gluten was injected under the skin of DH patients, and it did not produce blisters, because DH is not a skin allergy to gluten. However, if a Dermatitis Herpetiformis patient takes gluten by mouth, lesions can then appear as DH blisters on the skin. Dr. Marsh in Manchester (England) introduced gluten into the rectums of patients and in several instances the patients claimed that attacks of DH followed.

What happens when a DH patient ingests gluten? In the intestine the body’s immune system mounts a response to the gluten. Part of that response is the production of antibodies, which are little chemical messengers the body produces in defense. In DH patients those antibodies often get dumped under the lining of the skin, where they sit like small land mines for days, months, or years. Then one day something triggers them (sunlight, iodine in a cleanser, etc.) and there follows a bursting forth as the skin’s immune system begins attacking the deposits, thereby forming the blisters. But the deposits occur originally when the intestine is exposed to gluten.

DH is the skin manifestation of intestinal gluten sensitivity that is indistinguishable from CD. Most, if not all, DH patients will have some degree of damage in their small intestines, even if they may have no gastrointestinal symptoms.

         Q. Is the danger of intestinal cancer as high with DH if the patient is not completely compliant to     the GF diet?

A. "It is probably not quite as high in DH as in CD, but it happens; and there still is occurring an excess of lymphoma patients, especially in middle-aged men."

Q. Can you have dermatitis herpetiformis (DH) without having CD?

A. If you have DH, then you have an intestinal sensitivity to gluten that will cause some damage to your intestine and may become more significant as you get older. The treatment for both CD and DH is a  GF diet. If you have DH you may...find some relief from  dapsone, a medicine that suppresses the symptoms until the diet takes effect.

Dr. Murray is convinced that ALL Dermatitis Herpetiformis [DH] patients also have Celiac Disease, whether they realize it or not. This (type of) Celiac Disease is often latent or silent. Earlier reports of patients with DH who did not have enteropathy may not have counted milder forms of the celiac disease damage.

Since CD is an autoimmune disease, it follows that there are other autoimmune diseases that are associated with it. Rheumatoid Arthritis, Lupus, Type 1 Diabetes, and some eye problems occur more frequently in CS patients. This is not because of gluten or CS itself; it is because CS patients are part of a group that is genetically predisposed toward auto- immune complications.

About 5% of CD patients have DH. At the University of Iowa, there have been 350 patients diagnosed with DH, which Dr. Murray believes have celiac disease. If DH patients are only 5% of the Celiac population, then there would be approximately 7,000 Celiacs in the Iowa area. The number of diagnosed Celiacs is much less than 7,000. Even if this extrapolation is exaggerated, it is still clear that there are many undiagnosed Celiacs in the general population.

Most DH patients are prescribed Dapsone, which treats the symptoms. In many cases, patients are told of the  GF diet, but it is not stressed and so most do not follow it.

Dr. Murray finds this most distressing, because even if DH patients do not have GI-related symptoms, there is continuous damage being done to their small intestines.

Dermatologists in general don’t give enough consideration to a gastrointestinal involvement as the source of DH. This places DH patients at an even greater risk of developing lymphoma in the small intestine.

Lymphoma in the small intestine is extremely rare in the general population, while untreated Celiacs have a 70 or 80 times greater chance of developing it. A lifetime of being exposed to gluten gives a Celiac patient about a 7% chance of developing lymphoma. There is also an increased risk of other GI-related and lymphatic cancers. The risk of developing lymphoma immediately begins to decrease when the patient adopts the GF diet. The risk continues to decrease until, after 3-5 years, it approaches that of the general population.

Dr. Murray makes a small intestine X-ray a routine part of the treatment of a newly-diagnosed adult Celiac patient, especially those over 40 years of age. He is looking for lymphoma in the small intestine. It is difficult to detect, but if found can usually be successfully treated.

Dr. Joseph Murray, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905,  [507] 284-2763

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3. Associated Disorders

Diagnosis of Gluten Sensitivity: Time for a Change?

by KENNETH FINE, MD. Gastroenterology, Director of FinerHealth & Nutrition, and EnteroLab at WWW.intestinalhealth.org

What is the Difference Between Gluten Sensitivity and Celiac Sprue?

Gluten sensitivity implies that a person’s immune system is intolerant of gluten in the diet and is forming antibodies or displaying…evidence of an inflammatory reaction. When reactions cause small intestinal damage visible on a biopsy, the syndrome has been called celiac sprue, celiac disease, or gluten sensitive enteropathy. The clinical definition of celiac sprue usually requires a clinical and/or pathologic improvement following a gluten-free diet.

In the past, celiac sprue could only be diagnosed after certain symptoms developed. A biopsy of the small intestine would be performed and if abnormal and typical of celiac sprue, and if a gluten free diet brought resolution of diarrhea, with weight gain or growth, only then would a diagnosis of celiac sprue be made. However, recent advances in diagnostic screening tests and application of these tests to people at heightened risk or to general populations, have allowed earlier detection of celiac sprue, sometimes even before damage to villi has occurred. This latter scenario would…be called gluten sensitivity.

What Role Does Genetic Testing Play In the Diagnosis of Gluten Sensitivity?

Currently, tests are available to detect the genes that control the immune system's reaction to gluten. These genes are called human leukocyte antigens or  HLA. It is a particular type called HLA-DQ that is most useful in the assessment of the probability that a person may be gluten sensitive. The reason gene testing assesses probability rather than disease itself is because some people have the genes for gluten sensitivity but have no detectable evidence of the immune reaction to gluten or have no symptoms. In such people, gluten sensitivity is still possible but the probability is lower than in a person who may be having symptoms attributable to gluten or who has had antibodies detected.

Can I have gluten Sensitivity with Negative Screening Blood Tests?

With heightened awareness of the possibility of gluten sensitivity in family members of diagnosed celiacs, or in people with syndromes associated with celiac sprue, it has become clear that not all people suspected of being immunologically intolerant to gluten have positive blood tests. This is problematic…and is because the reaction to gluten begins inside the intestinal tract, not in the blood per se. I had an idea about a year ago that these antibodies should be more frequently detected in the stool of gluten sensitive individuals than in the blood. This turned out to be the case.

Who Should be Tested for Gluten Sensitivity?

Because my research has shown that as many as 40% of all Americans may be gluten sensitive, and from recent prevalence studies up to 1 in 150 have the severe form of this sensitivity causing celiac sprue, a case can be made that  everyone in America should be tested for gluten sensitivity  (similar to the concept that everyone should have their cholesterol checked to ensure they are not at high risk for having a heart attack). However, there are people with various risk factors or diseases who are at greater risk and should undoubtedly be tested.

ASSOCIATED DISORDERS, Kenneth Fine, MDPeople with the Following Conditions are at Increased Risk for Gluten Sensitivity/Celiac Sprue: 

Relatives of gluten-sensitive individuals

Microscopic colitis

Chronic diarrhea of unknown origin

Hepatitis C

Autoimmune liver disease

Other causes of chronic liver disease

Dermatitis herpetiformis

Diabetes mellitus, type 1

Rheumatoid arthritis

Sjogren's syndrome

Lupus

Autoimmune thyroid disease

Any autoimmune syndrome

Asthma

Osteoporosis

Iron deficiency

Short stature in children

Down's syndrome

Mothers of kids with neural tube defects

Female infertility

Peripheral neuropathy

Seizure disorders

Irritable bowel syndrome

Inflammatory bowel disease

Gastroesophageal reflux disease

Autism

AIDS

Kenneth Fine, MD, 10851 Ferguson Rd., Suite B, Dallas, TX 75228, [972] 686-6869

Down’s Syndrome

by Dr. Lloyd Rosenvold, 1992

Down’s Syndrome (DS) is a genetic birth abnormality that occurs in about 1:700 live births. The genetic defect is situated on chromosome #21 and at birth these children usually have 47 chromosomes instead of the normal 46.

The infants suffer from weakness, misshaped small heads and mental deficiencies. Most do well to have an IQ of about 50. Many die at a young age but some live on into middle life of 30s and 40s. General development is much slower than that of normal children. The facial appearance is Mongoloid and for that reason the condition is often referred to as mongolism. Other congenital defects and skeletal deformities are not regarded with surprise in these cases. There has been no treatment of value for these patients except to provide good custodial and nutritive care in order to make the best of a disappointing situation.

An Australian physician, Chris Reading, together with associates, has over a period of years carefully evaluated the family histories of more than 2000 patients. Among many of his discoveries relating to genetic data, he relates that out of the  18 children who had Down’s Syndrome, 17 positively had gluten intolerance. In the remaining case he suspected gluten intolerance in that child also.

Dr. Reading found that by placing the DS children on a gluten-free diet fortified with various vitamins and minerals he could report as follows: the DS children "have made rapid and measurable improvement in height, head circumference, weight, mental and motor development and general health."

Having observed that these children seemed to be deficient in various minerals and vitamins, and knowing that persons with gluten intolerance all have a malabsorption problem with nutrients, Dr. Reading fortified their diets with formulations featuring vitamins: B1, niacin, B12 and various minerals, particularly zinc.  Certainly if I had a Down’s Syndrome child in my family I would not hesitate to investigate whether or not the child also had celiac disease. There could be much to gain, and nothing to lose, investigating the possibility of there being a concomitant presence of celiac disease.

DS children should all be tested for gluten intolerance and if any are found they should be placed on a gluten-free program. In fact, it would be well for the mother to also be tested. We don’t know yet if any gluten-derived toxins might be transmitted in breast milk to an infant.  Lloyd Rosenvold, MD

To order Can a Gluten-Free Diet Help? How?  write to  Dr. Lloyd Rosenvold, % Mrs. Leola Rosenvold Box 330 Hope, Idaho 83836

Schizophrenia

by Lloyd Rosenvold, MD, box 330 Hope, Idaho 83836

CAN A GLUTEN-FREE DIET HELP? HOW? Republished 2001

For many years the cause of schizophrenia was shrouded in mystery. But a few decades ago it became evident that altered brain chemistry was involved and then followed suitable drugs that could modify the chemistry. A number of investigators have now demonstrated that diet and nutrition can be definite factors in causing the disease. In the Fall 1966 issue of Clinical Ecology, Beatrice Trum Hunter has made an extensive review of the literature on the topic. Here are some of her findings:

Is gluten Intolerance related to schizophrenia? Dohan (Dr. F. Curtis Dohan of the Medical College of Pennsylvania) thinks that it is. He has been studying the biochemical associations with schizophrenia. As early as 1966, he reported four observations:

1. Children with celiac disease, more often than by mere chance, become schizophrenic adults.

2. Psychoses occur in adult celiacs more often than by mere chance.

3. Gluten can induce common behavioral disturbances in both children and adults who are celiacs, and these disturbances subside after introduction of a gluten-free diet.

4. Often, during times of psychic stress or acute infection, the severity of celiac disease symptoms increases. In some instances, this is accompanied by an increased severity of schizophrenic symptoms.

Dohan suggested that in gluten-intolerant individuals, gluten may enter the brain and affect the nerve receptor sites. Peptides from gliadin may be the  neuroactive substances that go from gut to brain. Dohan's subsequent studies strengthened his original observations.

About ten years after Dohan's initial report, MM Singh and SR Kay of the Bronx Psychiatric Center studied schizophrenics who had been improved under neuroleptic drug therapy and who were on cereal grain-free diets.

When adding gluten foods they noted that the patients regressed in their improvement and after removing the gluten challenge they would improve again. Suitable control cases were maintained. They concluded that there were schizophrenia-promoting properties in the wheat gluten. (Their findings were reported in Science magazine 191:401-402, 1976.)

Other studies have demonstrated that where gluten-containing grains are freely used, such areas have a higher incidence of celiac disease than areas that are similar except for a lower use of the cereals.

Other  associated disorders Gluten-Free Friends, MCS Student Brochure, R. Jean Powell, Editor

The following disorders have a related incidence with Celiac Disease that is significantly higher than the general population incidence:

ADULTS: Arthritis, Chronic Anemia, Type II Diabetes Mellitus, Fibromyalgia, IBS, Infertility, Intestinal Lymphoma, Lactose Intolerance, Lupus, Osteomalacia & Osteoporosis, Multiple Sclerosis-type Neuropathy, Sjögren's Syndrome, Thyroid Disorders.

CHILDREN: ADD, Chronic Anemia, Type I Diabetes Mellitus, Down's Syndrome, Osteomalacia [Rickets], Seizures, Schizophrenia, Short Stature.

At Denver Children's Hospital, Denver, Colorado, pediatric patients with Diabetes Mellitus are routinely tested for Celiac Disease.

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4. Reproductive Disorders

Infertility by Dr. Lloyd Rosenvold

Millions of couples sorrow over their infertility—inability to bear children. Millions of dollars are spent each year of sophisticated tests and procedure to overcome or circumvent this disability. Individual couples may spend thousands of dollars in the process—at times fruitlessly. The problem may lie sometimes in the female, and sometimes in the male, partner.

A recent report from Ireland (Ulster Medical Journal 57 (1): 88-89, 1998) details a case of infertility of at least three years' duration. Merely two months after undertaking a gluten-free (GF) diet, the individual was able to conceive.

The investigators mention that there have been other cases of infertility (both male and female) with fertility restored by changing to a  GF diet.

We know of no extensive data on how dependable this method for overcoming infertility might be statistically. And in no way would we wish to lead to the impression that this method is a cure-all. But a trial of a  GF diet by both parties for several months might merit consideration, if it is seriously believed that there is other evidence that CD exists. Certainly the dietary trial costs essentially nothing but some diligent kitchen effort.

by Lloyd Rosenvold, MD: Can A Gluten-Free Diet Help? How? (2001 Revision) Box 330 Hope, Idaho, 83836

Celiac Sprue & Pregnancy 

by Gainer & Phillips The Journal of Perinatal and Neonatal Nursing (March 1993)

"Celiac disease patients present with signs and symptoms that may be divided into two groups, but all are due to malabsorption:

The first group of signs and symptoms is due to abnormal contents in the bowel and includes steatorrhea, diarrhea, and flatulence.

The second group of signs and symptoms is the result of a deficiency of dietary nutrients and is widespread and numerous, affecting every organ system.

In addition to a gluten-free diet, many celiac disease patients find they must use vitamin and mineral supplements. During the initial recovery period, intravenous and intramuscular vitamin and mineral supplements are often used to correct deficiencies because intestinal absorption has been disrupted.

Above all, the celiac disease patient needs health care from a provider familiar with the disease and its effects. The primary care provider must recognize that:

Celiac disease patients are susceptible to opportunistic infections and other disorders associated with impaired immune status.

Prompt attention and treatment are necessary when signs and symptoms suggesting infections or other pathologies present in the patient with celiac disease.

Knowledge about malabsorption disorders in general has come from the research on acquired immunodeficiency syndrome [AIDS], since AIDS causes malabsorption similar to that found in Celiac Disease.

In addition, celiac disease patients are more susceptible to opportunistic infections.

This is a serious problem, which is shared by AIDS patients.  Since Celiac Disease places these patients at risk for opportunistic infections, care must be taken to protect the [pregnant] woman from infections.  Chronic infections should be treated vigorously.

Dental care like that given to women with heart disease should be initiated. In addition, women must be protected from infections during the intrapartal and postpartal periods. The tendency to develop broncopulmonary infections requires vigilant assessment for signs and symptoms indicative of broncho-pulmonary disease.

Celiac Disease may first present in women during the child-bearing years as persistent macrocytic anemia or unexplained diarrhea during pregnancy or the postpartum period. Literature concerning CD in pregnancy is extremely limited and deals mainly with infertility and miscarriage. However, women who have severe celiac disease do become pregnant.

In general...the maternal and fetal outcomes can be good, but long-term effects for both the mother and the infant are not known. More research is needed.

Following are several points for the health-care team to keep in mind in planning care for the woman with celiac disease who is pregnant:

The disease might present for the first time during pregnancy, or it might be exacerbated during pregnancy.

The nausea and vomiting associated with pregnancy could place additional stress on the patient’s ability to deliver adequate nutrition to her own body and to meet the demands of the growing fetus.

The importance of meticulous maintenance of a gluten-free diet must be stressed.

Since the disease places these patients at risk for opportunistic infections, care must be taken to protect the pregnant woman with celiac disease from infections.

AVOIDANCE OF INFECTIONS:

Avoid exposure to illnesses.

Immunizations should be brought up-to-date prior to conception.

Chronic infections should be treated vigorously.

Dental care like that given to women with heart disease should be initiated.

Women must be protected from infections during the intrapartal and postpartal periods. The tendency to develop bronchopulmonary infections requires vigilant assessment...

Pregnant or postpartal CD women might be at greater risk for developing bleeding or clotting disorders.

Celiac Disease patients are able to breastfeed. However it is necessary to stress the importance of adherence to the diet to support needs of the mother for post-partum healing and the nutritional needs of the infant for growth.

The effect of pregnancy on the immune system coupled with the disease might place the pregnant woman with celiac disease at greater risk for problems. All celiac disease patients, women of childbearing age with celiac disease, and their infants should be considered at high risk and must receive careful, holistic, long-term care. For additional information for the use of your health-care provider, contact:

Gainer & Phillips, The American Celiac Society, 45 Gifford Avenue, Jersey city, New Jersey, 07304

If you’re considering Pregnancy...

Dr. Joseph Murray, of the Department of Gastroenterology, Mayo Clinic, Rochester, Minnesota provides advice for young women with Celiac Disease who are planning pregnancies:

Some cases of infertility are due to hormone deficiency.  Infertility in Celiac Disease is most likely due to hormone insufficiency, which causes an inability to ovulate. After becoming nutritionally well, the patient ideally should delay pregnancy for six to twelve months. This is time needed to give the gut a chance to heal.

There may also be a need to take  folic acid; research suggests that folic acid deficiency can cause neural tube defects such as Spinal Bifida. A Celiac woman who plans to have children needs to become as healthy as possible, taking folic acid from day one, when genes of the baby begin to develop, and even before becoming  pregnant if possible. The gynecologist should be visited in order to discuss diet and vitamin therapy, and to get any desirable vaccinations prior to pregnancy. Should she be really unwell she had best be on the gluten-free diet for one year before conceiving. This is an ideal scenario. Most women with Celiac Disease have borne healthy babies.

Being pregnant suppresses some Celiac symptoms, but because the skin is even more sensitive during pregnancy, Dermatitis Herpetiformis symptoms remain. The IgA [Immunoglobulin Antibodies] deposits sit like little land mines under the skin until they explode in blisters. They clear slowly. It can take a year to a year-and-a-half on the gluten-free diet for the skin to rid itself of the deposits.

Even though pregnancy reverses some Celiac symptoms, that is not an excuse to go off the diet. While thriving during pregnancy, Celiac mothers who have gone off the diet have been known to become sick immediately after delivery.

Dr. Murray also recommends that pregnant moms plan ahead by freezing "safe" foods throughout the pregnancy for use during their hospital stays; when first at home with their new babies; and for celebrations of the birth where there might be lots of tempting, forbidden treats.

A healthy baby needs to have a healthy Mom!

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5. Pediatrics

Typical & Atypical

Pediatric Presentations by Alessio Fasano, MD

Typical: The typical pediatric patient is 6 to 18 months old, is not thriving, and has symptoms of: Diarrhea, steatorrhea, poor weight gain, irritability, anorexia, all of which equal THE CELIAC CRISIS.

Atypical: Symptoms include short stature, enamel dysplasia, seizures, arthritis, DH, Diabetes Mellitus, stomatitis, nephropathy, thyroid disorders.

There are 3 important characteristics:

1. Celiac Disease is permanent. There are no cures.

2. Genetic Factors: we are genetically predisposed.  The familial occurrence in the general population is 2 – 4%; 12% in first degree relatives; 70% in identical twins.

3. Environmental Factors: gliadin avoidance controls the disease. Gliadin is a prolamin, an alcohol soluble fraction in cereal grains.

Short Stature: Twenty percent of idiopathic short stature in Europe is due to Celiac Disease. At the University of Maryland serum bank there were kids who did and did not respond to growth hormones. We analyzed these samples for IgG antigliadin antibodies. The kids who responded to growth hormone had normal antibody levels---some of those who didn’t respond to growth hormone had high levels of anti-gliadin antibodies, and all who agreed to the biopsy were found to have Celiac disease. Another example of misdiagnosis. Now children with short stature are screened for Celiac Disease with routine lab work.

Enamel Dysplasia: This discoloration is due to gliadin and gliadin antibodies on the matrix of the teeth. You can see the damage lines on the matrix of the teeth when gluten is introduced, then withdrawn, and reintroduced.

Seizures: Described to be frequently associated with Celiac Disease, due to intercranial calcification, particularly in the posterior of the brain causing seizures. We had a four-year-old girl with recurrent seizures who did not respond to anti-epileptic drugs and was brought to our office because of weight loss. She had had seizures for 2 years. She tested positive for the anti-gliadin and anti-endomysial antibodies.

The biopsy showed her to be Celiac, and for the first time her seizures were controlled. Folic Acid deficiency secondarily causes the calcification. Rarely does the calcium deposit almost disappear, but it did in this case.

Other Immune Disorders: Diabetes Mellitus, where the genes are on the same chromosome as CD, (the diabetic rate is much higher than in the general population); thyroid disease; Sjogren’s syndrome; Rheumatoid Arthritis, collagen vascular disease, and liver disease.

Mood Changes: Children come in crazy, screaming, yelling. A molecule seems to be involved in the internal control of subjects, and gliadin changes behavior by interfering with the inter-active receptors of endorphins. Endorphins are able to change the activity and alert(ness) of people. We calculated that there are 23,000 receptors per cell, in which alpha-gliadin could cause abnormal interaction.

Asymptomatic Celiac Disease: The person is healthy, with no symptoms, but has the typical intestinal histology. 12% of Celiac relatives have intestinal damage, and it is crucial that they be treated as Celiacs.

How do you make the diagnosis of Celiac Disease? In European Pediatrics it once was with 3 biopsies: 

1. Symptoms on a normal diet---Biopsy showing tissue damage. 

  2. Gluten-free diet for one year free of symptoms---Biopsy       

3. Challenge---Re-expose subject for 3 months or until relapse, then have 3d Biopsy.

This was painful for patients and physicians. Compliance was very poor, and it was a complicated process. We asked What can we do to improve this painful process?  The breakthrough was the use of anti-gliadin anti-bodies found in the lab in the early 1980’s.

There has been tremendous improvement of this assay:

         IgG sub class: highly sensitive, not very specific.

                   IgA sub class: not sensitive, but highly specific.

Anti-endomysial & anti-reticulin antibodies:  Highly sensitive and highly specific.

If Anti-gliadin and Anti-endomysial Antibodies are positive:   We are 99.6% sure it is Celiac Disease, the   Positive Predictive Value.

BUT THERE STILL NEEDS TO BE A BIOPSY!

The test is highly predictive so it is very useful for diagnosis. It is a different tool, considering the pain people were going through when three alternating biopsies and gluten-challenges were used. Tests on 3000 children showed that the same results were produced with the alternative approach as with the three biopsies.

Policy: To check antibodies once a year. If the child is showing high signals, then even though you thought the child was eating appropriate foods, you discover this is not the case.

Serological Screening: Anti-gliadin and anti-endomysial antibody screening shows a much higher prevalence of the disease than expected earlier. In Europe, there is a uniformity of incidence: 1:250. Why is it that, having the same genetic background in the US, we have such a difference in the incidence of the prevalence of the disease compared to European countries? Is this because we are different—or merely indifferent? At the University of Maryland we did a pilot study with 159 kids with atypical symptoms such as short stature, poor weight gain, and abdominal pain. Six kids were diagnosed with CD.

Reasons for the need to remain gluten-free: In Pediatrics, we as physicians have a tremendous responsibility---kids with Short Stature can recover totally their potential growth. But if we are late---too late---they will be short forever and ever, and it will be  our responsibility. Every single person with celiac short stature is a failure of a physician to make a diagnosis. The consequence of prolonged exposure is a much higher incidence of intestinal lymphoma, but after 5 years on a strict  GF diet, the difference is negligible within the general population.  Alessio Fasano, M.D.

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6. Neurological Summary

Neurological Abstracts, Cerebellar atrophy & Patchy demyelinization

Jerry S. Trier, M.D., Celiac Sprue Disease, CSA/USA Treatise:

Neurologic symptoms caused by lesions of the central or peripheral nervous system are not common in celiac sprue patients, but occur occasionally in severely diseased individuals. Muscle weakness, paresthesias with sensory loss, and ataxia are the most common symptoms encountered. Pathological evidence of peripheral neuropathy and very rarely, patchy demyelinization of the spinal chord, cerebral atrophy, and capillary proliferation...have been described.

Epilepsy, Cerebral calcifications, & Coeliac Disease:

The Lancet Dec. 10, 1994 v344 Author, William Dickey

Reports of an association between epilepsy and coeliac disease are not new. In 1966, Cooke and Smithill described "unexplained attacks of unconsciousness" in 5 patients, and Chapman et al twelve years later reported a prevalence of epilepsy among coeliac patients of 5.5%: 77% of their patients with epilepsy had what would now be called partial seizures.

In the largest [Italian] study, patients with epilepsy and calcification were screened for coeliac disease by small bowel biopsy, and 77% of 31 had characteristic villous atrophy. Conversely, 42% of 12 patients with coeliac disease and epilepsy had calcifications on CT screening. Although epilepsy preceded the diagnosis of coeliac disease in all patients with the syndrome, most had had symptoms in the first three years of life that accorded with malabsorption. Seizures ceased or were reduced in frequency by at least 50% in a third of patients after introduction of a gluten-free diet; patients whose seizures stopped were younger and epilepsy was of shorter duration when diet was started. Again, an early history suggestive of malabsorption was often obtained.

Growth failure, well recognized as a sole manifestation of coeliac disease, was a common finding in other reports. Some children had started a gluten-free diet in early life, which had not been maintained.

Neurological Manifestations of adult Coeliac Disease

The Lancet, Feb. 17, 1996 v347 Authors: David Beversdorf, Peter Moses, Alexander Reeves and John Dunn

Neurological manifestations of adult coeliac disease include cerebellar ataxia, sensory neuropathy, myopathy, hyporeflexis, and seizures. Dementia has more recently been added to this symptom complex, but in all of these patients the dementia has been unresponsive to a gluten-free diet. A suggestion was subsequently made that the symptom complex, exclusive of dementia, resembled that of vitamin E deficiency (ataxia, sensory loss, areflexia, and gait disturbances) and that replacement therapy should be attempted. Whereas diarrhea, steatorrhea, and weight loss are the most common (but not universal) clinical features of coeliac disease, the gluten-induced damage to intestinal villous epithelial cells results in malabsorption of fat-soluble vitamins, which can result in osteomalacia, hypocalcaemia, coagulopathy, and neurological abnormalities. Patients with abetalipoproteinaenemia, who lack the lipoproteins necessary to carry fat-soluble vitamins, develop a similar neurological symptom complex. These patients do respond to water-miscible vitamin E supplementation.

Does Cryptic Gluten Sensitivity play a part in Neurological Illness?

The Lancet, Feb. 10, 1996 v347 Authors: M. Hadjivassiliou, A. Gibson, G.A.B. Davies-Jones, A.J. Lobo, T.J. Stephenson and A. Milford-Ward

Many neurological manifestations are associated with coeliac disease, including ataxia, peripheral neuropathy, myelopathy, myopathy, and dementia. The original cases had severe coeliac disease. If...antibodies are directly or indirectly neurotoxic, why do patients with neurological dysfunction and on gluten-free diet not always improve? One possibility is that damaged neural tissue ( e.g, cerebella Purkinje cells) does not regenerate. The second is that patients may not strictly adhere to their gluten-free diet or that the diet may be insufficient to suppress the immunological process completely, especially since patients without gastrointestinal symptoms are unlikely to adhere to a gluten-free diet.

Antigliadin antibody estimation should be part of the routine investigation of any patient with neurological dysfunction of unknown cause.

New Research on the role of the Cerebellum in Cognitive Functions

DISCOVER MAGAZINE NOVEMBER 1996 Volume 17 Number 11

"...Neuroscientists are finding that both motor and cognitive tasks may in fact be processed in the same part of the brain. The site of the action consists of two fist-sized clumps of tissue at the base of the brain called the cerebellum, from the Latin for  ‘little brain’."

Until recently, researchers thought the role of the cerebellum  was solely to regulate the speed, intensity and direction of movement. Dr. Henrietta  Leiner "began to suspect that the cerebellum might play a role not just in movement but in cognition--that is in those processes such as language by which humans come to know, and make judgments about, themselves and the world around them.

Peter Strict and his colleagues at the Veterans Affairs Medical Center in Syracuse, New York, have traced a pathway in monkeys from the cerebellum back to parts of the brain that are involved in memory, attention, space perception, body positioning, and spatial guidance. These diverse findings coincide with one neuroscientist’s theory about the origins of autism. Since 1985, Eric  Courchesne of the University of California at San Diego has been proposing that autism is linked to cerebellar deficits. His own brain imaging studies have found smaller cerebellums in autistic children; and fewer cerebellar neurons have been found by other researchers.

Autistic-like Tendencies in a Celiac Child

GLUTEN-FREE FRIENDS, Montana Celiac Society Newsletter, 1992 & 2001

Anthropologist Tamala Powell describes an eight-year-old boy who was diagnosed with mild autistic-like tendencies after exhaustive tests by a  neuro-psychologist. The boy suffered from mood swings, irritability, and frustration with school experiences. At times easily distracted, conversely he could exhibit an intense, uninterruptible concentration, lacking an ability to acknowledge outside stimuli.  He could not make a smooth transition from one focus to another. He had difficulty with spatial concepts and was unable, in his drawings, to account for the size either of the sketch or the paper, causing the figures to drift off the page.

Being unable to integrate individual concepts into a whole, his drawing of a person and a tree might depict the person as being larger than the tiny tree. Once diagnosed with Celiac Disease and adopting the gluten-free diet at the age of eight, the twelve-year old now has few such residual tendencies, although he exhibits occasional emotional stresses from his negative experiences. Not only has he adapted tools for compensation, he better relates to environmental stimuli and can filter out distractions. He concentrates more appropriately. His improvement has been remarkable, and he enjoys normal cognitive function in school.

Update: Now 17, this young man has grown from an underweight and short  statured eight-year-old to a 6 foot 2" tall young man who is healthy and capable in his environment. There is no residual evidence of his challenging history as long as his diet remains under control.

SUGGESTED READING:

NOBODY NOWHERE, by Donna Williams. The author is autistic. Her childhood memories and brilliant insights are detailed in this autobiography. The book encourages compassionate treatment of autistic children by expanding a comprehension of their startling needs. Williams implicates nutritional malabsorption as an exacerbating factor.  Avon Books, Inc. 1998 RJP

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7. Dental Defects

Dental Defects Associated with Celiac Disease

Gluten-Free Friends, Research Resource by Cleo Anderson

"In 1998, Dr. Lissa Aine and the Finnish Dental Society conducted a study that discovered that enamel defects (hypoplasia) found in systemic patterns correlated significantly with both gluten ingestion and severity of symptoms in children with celiac disease. The maxillary permanent central incisors were affected in 95% of the celiac children studied who had permanent teeth. Both initial gluten ingestion and subsequent gluten challenge prior to the age of 3 years could be clearly seen as enamel defects on the maxillary permanent central incisors. Both dental maturity and skeletal maturity were delayed in celiac children when compared to controls. 'Catch-up' growth in dental tissues and bone occurred in celiac children on a gluten-restricted diet. Suggestions for decreasing the adverse effects of gluten ingestion and the subsequent immune response on dental development are given.

This study further found that prior to the diagnosis of celiac disease, malabsorption affects nutrient status and the immune response system is on 'red alert'. When undiagnosed, celiac disease effects occur at the same time as critical tissue development and the resulting tissue may reflect the nutrient deficiencies and/or abnormal immune response.

For part of the study, they studied 86 children ranging in age from 3 to 22 years who had biopsy-proven celiac disease (41 boys and 45 girls). Ten of these children had only deciduous teeth, 45 had various combinations and the remaining had fully developed permanent teeth. Control subjects were used for both the dental enamel defects portion and the dental maturity segment. Dental enamel defects (hypoplasias) were studied using systematic observation, photography and dental casts. In the children with only the 'baby teeth', x-rays of the first permanent molars were studied to determine the degree of enamel defects. Dental maturity was estimated from both clinical eruption of teeth and from a score obtained from full mouth x-rays of seven left upper teeth. The results showed that of the 76 celiac children with permanent teeth, 73  (96%) had dental enamel defects. This compares with 47 (31%) of the 150 clinical controls. Of the celiac children with enamel defects, 75% of their permanent teeth were affected, compared to only 8% in the control subjects. In the celiac subjects, at least two groups of teeth, incisors and molars, were affected.

Enamel defects in celiac children usually occurred as bands that encircled the teeth. The enamel defects occurred during the same time span, thus emphasizing the systemic nature of the enamel deformity. The two upper front teeth (maxillary permanent central incisors) were always affected. This is understandable, since 90% of the enamel of these teeth develops between 10 months and 4 years--when the malabsorption and immune response in undiagnosed celiac disease is unchecked.

It is not known whether it is the malabsorption or immune response that is primarily responsible for the enamel defects. While the enamel defects in the teeth of those with celiac disease were symmetrical and time-related, the enamel defects in the control children were not symmetrical or systematic.

Also to be noted is that the severity of the enamel defects was greater in celiac children than in the control group. Twenty-nine percent of the celiac children had evident or severe defects as compared to less than two percent of the control subjects.

Enamel defects proceed from the tip of the tooth towards the area that will be situated near the gum line. Therefore, a fairly accurate estimate can be given of when the enamel defects occur. Using the upper two front teeth as a time-line indicator, the effects of gluten ingestion was studied as well. For the 14 of 16 children who were diagnosed before the age of 2 years and had strictly followed the diet, the enamel area formed last, adjacent to the gum, was not affected, although the preceding enamel areas were. In the 10 of 11 who had been diagnosed and then taken the gluten challenge before the age of 3, enamel defects occurred in the gingival portions of the tooth enamel as well as other areas. Twenty-eight of the 39 diagnosed after the age of 4 showed severe enamel defects. Eighteen had enamel defects in all three areas of the upper front teeth, 10 had enamel defects in the medial and gingival areas.

An interesting issue was discovered during this study: there appeared to be a direct correlation between the severity of the clinical celiac symptoms and the dental damage in the 76 children with permanent teeth before the age of 4. The more severe the symptoms, the more severe the enamel defects

When the dental maturity was measured, those with celiac disease were delayed in comparison with the control group. Children with CD had later eruption of their permanent teeth. The bone age of the celiac children was retarded compared to the control group."

CLEO ANDERSON, Helena, Montana, State Coordinator: CSA/USA

Finnish Dental Society Study, 1988, Dr. Lissa Aine.

Published 5/98 in Montana Celiac Society Newsletter, Gluten-Free Friends

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Presentation by Dr. Joseph Murray

Dr. Murray, Mayo Clinic,  addressed Montana Celiac Society 

on August 7th, 2004, at Billings Deaconess Hospital. 

Transcribed by R. Jean Powell for Gluten-Free Friends

 Celiac Disease in the 21st Century

A History & Time Line: Celiac Disease has been known for 14 millennia. Wheat was first cultivated in Asia Minor in about 11,000 BC and the first description of the disease was by the Greek physician Aeritaeus (sp) of Cappadocia, who called it the "Coelica" or "bellyacher" in his first textbook. He gave a very exacting description of what CD was, including the form of the stools, its appearance in children and in adults and, while he made the suggestion that it had something to do with food, he didn't know what.

The next detailed description was by Samuel Gee in 1888, who basically wrote in his treatise what Aeritaeus had said, but with more modern information.  He called it the Coeliac Affliction.  Gee said that the answer to the Coeliac Affliction and its treatment must reside within the diet, but the components were not known. In the 1920's, Haas came up with the so-called banana diet, but felt that certain complex carbohydrates were the problem. Nevertheless, his diet worked; I've seen a few patients who survived because of the Haas diet. 

It wasn't until the 1940's that a Dutch pediatrician named  Dicke observed that his pediatric patients, who usually were hospitalized for long periods and eventually wasted away, thrived during times of starvation throughout the Second World War. When the children began experiencing periods of sickness after the war, Dicke was humble enough to ask his cook if she had done something differently, and she noted she had received an order of flour that she made into wonderful soda cakes and bread for the children. Dicke put two and two together, realizing that what was good for the others was not good for the kids with celiac disease.

        In the 1950's Pauley and others described the changes and damage that occur in the small intestine; and in the 1960's very inventive people developed ways to "fish out" pieces of intestine without having to operate on patients.  The endoscope appeared. In the 1980's and 1990's, a whole series of discoveries appeared regarding the science of CD: Gliadin antibodies, HLA blood type, endomysial antibodies, and the role of T cells, which are a particular part of our immune system that seems to have a central role in the causation of CD.

In the early 1990's the concept of the iceberg arose, which showed that 95% of Celiacs in Europe were being missed--and so even more were being missed here in the US.

In the 21st Century in trying to unravel this disease, we're moving into a new era scientifically: understanding the role of tissue transglutaminase, the role of genetics and genomics, and the role of what are called innate responses. In the 21st Century in trying to unravel this disease, we're moving into a new era scientifically: understanding the role of tissue transglutaminase, the role of genetics and genomics, and the role of what are called innate responses.

What IS Celiac Disease?  The normal villi of the small intestine are similar to a shag carpet, and greatly expand the digestive working surface. It is along the surface of the villi where the digestive enzymes and absorption occur.  If ironed out, the absorptive surface of a healthy small intestine would cover 2 tennis courts, but the gluten-damaged villi would shrink the absorptive surface to the size of a kitchen table. Celiac Disease is an inflammatory state of the small intestine that occurs in genetically predisposed individuals.  Not everyone who has the genes gets the disease; it occurs in just a few of those who are genetically predisposed, and the damage resolves with the exclusion of gluten. The underlying process does not.  If you reinstitute gluten into the diet the damage reoccurs, producing a flattened surface with a greatly inflamed thickened basement or crypt layer in the small intestine.

What Causes Celiac Disease?  The cause is a combination of genetics and environmental factors with the major cause being gluten--but there are others.  When all those come together you get an immune response against gluten. That immune response gets out of control and it turns into inflammation and damage.

Another way to look at it is as a collision between our cultivation of wheat and the immune system, particularly what is called our Human Leukocyte Antigen Recognition System (HLARS), which is what makes us uniquely human.  This system helps us to survive in a hostile environment.  It identifies bacteria, viruses, and our own cells that have gotten infected with viruses, and HLARS kills the cells in order to kill the virus.  It determines our ability to recognize self from non-self, so that transplant recipients must take drugs to prevent the immune system from attacking foreign tissue. It is an exquisitely, finely tuned system for differentiating self from non-self. Another way to look at it is as a collision between our cultivation of wheat and the immune system, particularly what is called our Human Leukocyte Antigen Recognition System (HLARS), which is what makes us uniquely human.  This system helps us to survive in a hostile environment.  It identifies bacteria, viruses, and our own cells that have gotten infected with viruses, and HLARS kills the cells in order to kill the virus.  It determines our ability to recognize self from non-self, so that transplant recipients must take drugs to prevent the immune system from attacking foreign tissue. It is an exquisitely, finely tuned system for differentiating self from non-self.

Why is Wheat Harmful?  Wheat is probably one of the most important crops in the temperate world, matched only by rice. Wild wheat preceded man by a hundred million years. We have changed it but little by cultivation. The outside of the wheat kernel is the bran or fiber; the endosperm or inside is a storage compartment.  The seeds' stores need to have energy, and protein or nitrogen are sources for when the germinal center erupts or germinates.  The germ is made up of protein and lipid, but it's not the same protein.  The proteins of gluten that are damaging for celiacs are gliadins or glutenens contained in the endosperm compartment. It has been pointed out to me by a cereal chemist that this is very much a compartment.  The germinal center separates itself from the storage compartment because some of the proteins may be damaging to the seed before it starts the germination process.    

            These proteins are uniquely high in amino acids, which are the building blocks of every protein.  About 35% of the amino acids in wheat proteins are glutamines, and they are especially high in prolines.  There is a particular sequence, almost a code, of the amino acids that occur in wheat, barley and rye, which appear to be toxic to celiacs.   So it's a very specific code.  It is not just in one part of the protein; the code is repeated multiply throughout the proteins. 

            Glutamines are an excellent store of nitrogen. The plant likes them because they store double the amount of nitrogen compared to many other amino acids. The glutamines can be cross-linked or stuck together, which gives the grain its resiliency.  It's the glue that gluten is derived from that gives wheat bread its shapes.  Prolines, the other amino acids, together form spirals that make this protein particularly resistant to digestion in the mammalian gut. We are not good at breaking down proline twists. It appears to be the coincidence of the proline twists plus the glutamines in certain sequences  that seem to trigger a response in certain people.

  Genetics:   In at least 50% of families with their first diagnosed member with celiac disease, you will find a second person affected by the disease.  If one identical twin has the disease there is an 80% chance that the other twin will have the disease as well.  That tells us that there is a very strong genetics' influence, but it also tells us that there is an environmental influence, because the other 20% do not have the disease.  Siblings,  brothers and sisters, have about a 10% chance, although that varies depending on how closely related they are in regard to their HLA type. By sharing the same HLA code as the affected sibling, the risk is about 30% rather than 10%. 

If you're the child of a celiac, it's about a 5 to 10% risk.  If you are a connecting parent with a child with CD as well as a mother or an uncle with CD, your risk is much higher, about 25%.  If you're not a connecting parent your risk is probably only 5%. We know there are certain HLA genes, either DQ2 or DQ8, that are required--but they are not sufficient. There are lots of people who have these gene types and don't have the disease.  Several other genes are suspected, but have not yet been confirmed.  And there are individuals who have certain chromosomal abnormalities such as Down's Syndrome, Turner's Syndrome, and Williams' Syndrome, whose risk for CD is about 10 - 15%.  It is not because of the HLA types but because of a predisposition to CD and other autoimmune disorders caused by their chromosomal problems.

 Triggers: So we've got a collision between certain gliadin peptides [Def: 10 or more amino acids]  that arrive at the gluten that reaches the gut when we eat wheat; and we've got this HLA type that our immune system can recognize.  But is there a trigger?  Thirty percent of the Caucasian population has these HLA types; and other than celiacs, 99.5% of the population eat wheat.  So what are the triggering factors? 

We know a little about those.  We know for example that pregnant women following delivery have a hyped up immune system that has been suppressed during pregnancy in order to accommodate the foreign body she carries that is the child, who is a separate organism immunologically.   Immediately following delivery, the immune system is turned right back on again.  That was important in evolution, because the newly delivered mother is prone to infection.  That's one trigger that can occur.  The second is a major operation or a major shock to the system that can turn on the immune system to recognize Celiac Disease.

Tissue Transglutaminase: Tissue Transglutaminase is an enzyme that is present in the gut.  It is involved in tissue gluing, which keeps some of our cells stuck together.  Now we say, hmmm, where did we see the terms glutaminase or glutamine before?  Well, TTG cross-links glutamines, so it's actually transglutaminating glutamines.  So low and behold, the same enzyme which is meant to be a glue enzyme within our tissues also changes the gluten, making it more toxic to people with Celiac Disease. So this is probably one of the major collisions or triggers between gluten and the gut and the immune system.

           There are several ways tissue transglutaminase can be turned on.  A bad dose of gastroenteritis or GI flu  can turn it on.  Crackers or toast for a diarrheal illness is the worst possible prescription for some one with diarrhea.  Why?  The person is being loaded with something that is potentially toxic!  It's not particularly digestible either--and at a time when the TTG enzyme is turned on in the gut for another reason.

  The Celiac Process: To put this together in a schema, we start off with wheat, which contains the gluten/gliadin fractions that are particularly antigenic [Def: Capable of stimulating an immune response].  The fractions are ethanol-soluble [Def: Ethanol is the intoxicating agent in liquors; a solvent], which is how they are separated chemically.  The fractions are taken up across what is probably a normal epithelium [Def: A membrane that lines a tube or cavity], and are broken down into smaller bits that get changed by the TTG or tissue transglutaminase enzyme, into what we call deamidated gliadin. [Def: Deamide: A compound containing two amino groups]. Diamidated gliadin is then taken up by scout cells that expose it to the T Cells.  They are supposed to respond after doing the analysis, producing both lymphocytes, which are the cells that do a lot of the actual damage, and plasma cells, which produce antibodies.  We're not sure how much damage these antibodies are causing, but they are useful from the point of view of diagnosis.  Lymphocytes seem to cause most of the damage to the epithelium. [Definitions from the Merriam Webster Collegiate Dictionary].

There are other things to be aware of such as the villi, which need a structure or scaffolding inside in order to stand up. During the celiac injury that scaffolding is taken apart.  Enzymes actually smash up the skeleton, literally taking it apart so the whole thing collapses on itself.

The other thing that can happen is that cells on the surface are stuck together in a tight junction making a very tight barrier between the inside of the gut and the body.  In Celiac Disease, these tight junctions pull apart and become permeable, which is sometimes termed Leaky Gut Syndrome. Gliadin can then pass freely between the cells and be taken up by the antigen presenting cells or by those scouts within the lining of the gut.

  How Common is Celiac Disease? Is the US any different from Europe?  There is lots of CD diagnosed in Ireland because it's been well-known among general practitioners, family doctors, and pediatricians, and others that Celiac Disease is a common disease.  But even in Ireland, many go undiagnosed, perhaps even the majority, just as in Finland.  In 1996, diagnosis in the US was just .2 per thousand, that's 1 [person] per 5 thousand.  This was in Olmstead County in Minnesota, where we have the highest concentration of gastroenterologists in the world at the Mayo Clinic.  In another study from Baltimore, the ratio was 4 per 1000, where they tested 2000 blood donors for markers of CD, (MCS was a part of that study under the direction of Dr. Fasano).  In Denmark in 1996 the number was remarkably low at .45 per 1000.  These numbers have been radically changed even in the last 5 years in Denmark, Sweden and Italy, so it is not that rare, especially among adults. 

Also in 1994 in Olmstead County, Minnesota, which has a population of about 100,000, Nick Talley, one of my colleagues, published the lowest prevalence of diagnosed Celiac Disease in the world, with .8 per 100,000!  We were diagnosing less than one person per 100,000 in that population per year.

            Blood testing for serology was simply not used until the mid 1990's. Updated data for 2001 shows a dramatic increase of new cases through the mid-1990's and into 2001, dramatically different from the 3 decades before.  The itchy, blistering skin rash, Dermatitis Herpetiformis, or DH, showed rates that didn't change much in that time because dermatologists made the correct diagnoses--Mayo also has the largest number of dermatologists per square mile in the world...                            

If one were to iron out the surface of a healthy small intestine, it would cover 2 tennis courts and that is the surface that is capable of absorbing nutrients in a healthy small intestine. Shaved and flattened it would shrink to the size of kitchen table in the gluten-intolerant small intestine.

Celiac Disease in the US affects more Adults than Children! More women than men are diagnosed. It occurs world-wide, but it involves mostly Caucasians and can affect any age, including the elderly.  It particularly tends to have an effect on people who have other immune disorders or have a family history of other immune disorders: Type 1 Diabetes (Juvenal onset Diabetes), Sjogren's Syndrome with drying of the mouth and eyes, often associated with enlarged glands, Thyroid disease, Lupus, Addison's disease; and it also affects family members of those who have Celiac Disease.

How Does it Present? Following is the classic presentation in children: it starts slowly or insidiously after gluten is introduced, somewhere between the ages of 6 months and 7 years, and that age of new diagnosis is getting older in children.  Seven, eight, nine years is not unusual for diagnosis, whereas typically before it was one or two or three years of age. The child often fails to thrive, has abdominal distention (often with a little 'outie'), and a very poor appetite. In adults you sometimes see the opposite, polyphagia, where people eat a tremendous amount of food and never seem to gain weight.  There is also steatorrhea  (the sour-smelling stools with a high fat content), anemia, growth failure and vitamin deficiency. 

However, that is only about 25% of the presentations.  About half of new cases have only one symptom: just diarrhea, just anemia, just lactose intolerance, or just constipation. One single symptom, not multiple symptoms.  A few patients come into the emergency department with severe abdominal pain or intussusception, a folding of the bowel into itself, with vomiting, obstruction, even perforation of the gut, or in a few unfortunate people, lymphoma.  If somebody presents with an acute abdomen and Celiac is not diagnosed, there is a pretty high mortality rate.  I occasionally hear of people who've died of Celiac Disease who've had this type of presentation with diagnosis not made until very late. But that's relatively rare now.

Then there are the non-GI presentations, people who don't have any GI complaints, but have infertility, bone disease, neurological problems, short stature, brittle Diabetes, chronic fatigue, abnormal liver blood tests--there is a whole host of other things that can be a presentation of Celiac Disease. 

Now it's interesting that when you talk to those patients after they've gone on a gluten-free diet they might say "You know, I did have 3 or 4 bowel movements a day and they did float, but I never thought it was abnormal, because that's the way I've been all my life!"  So even though you might say they didn't have any symptoms--a symptom being something you complain of--they really did have GI problems.  They just weren't aware that it was abnormal.  Very few Celiac patients have steatorrhea--most do not.  

What about deficiency states?  Fat-soluble vitamins are D, E, A, and K. D is important for bones so a deficiency in D can cause osteomalacia or myopathy. Basically that causes bone pain when you stand on your bones, especially in the hips, (which typically get better when you lay down), and muscle weakness and pain in the shoulders and hips; Vitamin E can be associated with certain neurological syndromes; Vitamin A can cause problems with night vision; Vitamin K, with bleeding such as nose bleeds.  Iron deficiency is probably the single most common deficiency, because iron is absorbed in the first section of the small intestine. Folic acid and B12 deficiencies are common, plus zinc, and B6, but those deficiencies probably occur only in the sickest of patients.

What about Irritable Bowel Syndrome?  Five percent of patients referred for irritable Bowel Syndrome have Celiac Disease. There is also a condition called gluten-sensitive diarrhea.  It's not well-studied or understood, but it's probably an explanation of why there are a lot of people who have symptoms and are tested for Celiac Disease but totally do not have it However, their symptoms do get better on a gluten-free diet. This condition [is called] gluten-sensitive diarrhea. Five percent of patients referred for irritable Bowel Syndrome have Celiac Disease. There is also a condition called gluten-sensitive diarrhea.  It's not well-studied or understood, but it's probably an explanation of why there are a lot of people who have symptoms and are tested for Celiac Disease but totally do not have it However, their symptoms do get better on a gluten-free diet. This condition [is called] gluten-sensitive diarrhea. Five percent of patients referred for irritable Bowel Syndrome have Celiac Disease. There is also a condition called gluten-sensitive diarrhea.  It's not well-studied or understood, but it's probably an explanation of why there are a lot of people who have symptoms and are tested for Celiac Disease but totally do not have it However, their symptoms do get better on a gluten-free diet. This condition [is called] gluten-sensitive diarrhea.

Symptoms of diarrhea and abdominal pain are common, of course, in Celiac Disease and in Irritable Bowel Syndrome.  The difference from the medical perspective is that we really have not been aware that abdominal pain is a major feature of Celiac Disease, but it certainly is. It affects at least three-quarters of people with Celiac Disease, whereas Irritable Bowel Syndrome is defined around abdominal pain and disorder bowel habits. So again it's been a perception issue.

Irritable Bowel Syndrome affects about 10% of the population, Celiac Disease probably a little less than 1%. So if the doctor gets it wrong, he still is probably getting it right about 95% of the time, just based on numbers alone. If you look at people who have the diagnosis of Celiac Disease, and at those who have criteria that would match Irritable Bowel Syndrome, they [both] get better on a gluten-free diet

  What About the Numbers of People with Classic Symptoms?  They've gone up!

  Why is Celiac Disease in the US so Different from any European Countries?  In some European countries where there's a high gluten content in baby food, the typical onset is between one and three years of age, whereas here, it's now 55 years of age and we see very little pediatric disease. 

That's probably because of our standards of progression of solids in the diet.   

  What are other Factors that affect Celiac Disease?  Menstruation, for iron-deficiency in women, of course, and then onset of malignancy in a few unfortunate patients later in life.  There are some other places Celiac Disease pops up--in dental surgery for example, where you see discolored teeth with little notches on them; this is from deficiency of calcium at the time the permanent teeth were being formed.  There are other places where it presents: neurological and even psychiatric symptoms; abnormal liver blood tests; fibromyalgia and chronic fatigue, which are very common; skin and mucus membranes, especially ulcers or canker sores within the mouth. They are quite common as a presentation in Celiac Disease.  Menstruation, for iron-deficiency in women, of course, and then onset of malignancy in a few unfortunate patients later in life.  There are some other places Celiac Disease pops up--in dental surgery for example, where you see discolored teeth with little notches on them; this is from deficiency of calcium at the time the permanent teeth were being formed.  There are other places where it presents: neurological and even psychiatric symptoms; abnormal liver blood tests; fibromyalgia and chronic fatigue, which are very common; skin and mucus membranes, especially ulcers or canker sores within the mouth. They are quite common as a presentation in Celiac Disease. 

Dermatitis Herpetiformis is part of Celiac Disease. A typical case shows a blistering rash on the knees, elbows, buttocks, the back of the hairline, (if you have hair...).   Dermatitis Herpetiformis is caused by gluten in the gut, not by rubbing gluten on the skin--you can't set off Celiac Disease by using a wheat germ shampoo unless you swallow the stuff!  Similarly, you can't set Dermatitis Herpetiformis off by rubbing wheat on the skin--you have to take it in the gut in order for it to trigger the skin disease.

We know that Celiac Disease and Type 1 Diabetes have been reported together for more than 50 years, and there are a lot of studies now of children and adults with Type 1 Diabetes.  CD affects somewhere between 3 and 10 percent of Type 1 Diabetics.  It rises with age.  All of those diabetics carry either DQ2 or DQ8 .  If you look at family members of somebody with Type 1 Diabetes, you will see that they are more likely to have Celiac Disease.  And it's probably because both Celiac Disease and Type 1 Diabetes largely have the same genetic predisposition.

  Where is Celiac Disease Hiding?  In people of all ages with an iron-deficiency, a so-called Irritable Bowel Syndrome, bone disease, Type 1 Diabetes, abnormal liver blood tests, unexplained infertility, and those relatives of Celiacs who haven't been tested, etc.   The list goes on and on. 

  What about Testing Family Members?  Certainly I believe we should test family members if we have an index case--that's somebody with diagnosed, confirmed Celiac Disease.  Not suspected Celiac Disease, but confirmed Celiac Disease.  The family members to be tested must be on a normal diet.  They can't be on a gluten-free diet.  The ideal age is starting at about the age of three.  Serology or the blood test picks up most, but not everyone--there are a few who might be missed.  I would consider biopsying a family member who has a lot of symptoms suggestive of Celiac Disease, even if their serologic testing is negative.

            One of the down-sides of doing the genetic test for Celiac Disease is this: If you're a family member of a Celiac, you are highly likely to carry those genes anyway.  Sixteen to seventeen percent of family members will carry those genes.  Most of them will never get Celiac Disease.  I frequently see people who are misled by the genetic testing,  "Oh, I've got the gene, I must have celiac Disease."  That is NOT true!    Most of the people who have the gene do not have Celiac Disease, even if they are a family member.  You need more than that to know that you've got the disease. 

If you have the gene, it means you could potentially get the disease, but if you reach the age of forty, it's very unlikely that you're actually going to get it if you haven't gotten it by that age--or perhaps even younger yet. There are other issues with doing the genetic testing in families.  One, it is a genetic test.  Genetic counseling may be necessary to explain what I said, "A positive test does not equal the disease."

There are negative consequences of a positive genetic test, such as labeling people even though most of them will never get it.  And you'd think those who are ruled out would be happy, but interestingly, there are few family members who are upset because they feel guilty.  If among 4 or 5 siblings one of them is told that they don't have the gene for it, they feel guilty that they don't and the others do.  Paternity issues even crop up occasionally.

Who should We Screen for Celiac Disease?  The large University of Maryland study, which they carried out across the country, (Montana Celiac Society participated in 1999) showed that the rate of Celiac Disease was .78 of males per hundred, which is just under 1%, .72 per hundred for females, and for adults, .95 or just under 1%.  One in one hundred of healthy individuals had markers for Celiac Disease.  It was lower in children: 1 in 300.  And that's probably because children are going to accumulate Celiac Disease up to about the ages of 7 or 8. Once they get to 7 or 8, probably most people who are going to get it have it, but the vast majority have not gotten enough of it to be sick yet.

  How much Celiac Disease is there in the general population?  In the Casper, Wyoming study there must have been at least 25 people involved who made it possible.  We participated by doing the blood testing. Gastroenterologist Ken Kaatz, Casper, was the principal investigator in Wyoming for the study.  They wanted to determine what the prevalence of undiagnosed Celiac Disease was in Natrona County, which is the county surrounding Casper, and to identify associated symptoms that might predict Celiac Disease.   They also wanted to determine what the acceptance of the general population of this type of testing would be as part of the Health Fair testing--I don't know if there is Health Fair Testing in Montana, is there?  (Yes.  Eloise Faber of  Manhattan will be exploring the possibility for us, Ed.).  Health Fair testing seems to be a real tradition in Wyoming.  Basically people go there to get blood tests for a variety of things, go to a Fair on a Saturday afternoon in the middle of March--is March still winter here?  It is very much still winter in Minnesota!  They go to get health prevention or health promotion information at the Health Fairs.

            We invited everybody who participated in the Blue Envelope Health Fair, Casper,  to participate in the blood drawing, and 4100 of those, about 82%, completed a standardized questionnaire and provided a serum sample.  Some of them were there to have other general blood tests done.  This is the Fair in action, with volunteers giving out information and people filling out forms as they are waiting in line.  There were 4040 adults, Natrona County residents, who participated.  They all had the Tissue Transglutaminase Antibody Test, with the kits provided by a crowd in Birmingham, England and then we did the Endomysial Test to confirm the positives.  Everyone who was double positive was followed up and offered the opportunity to have a biopsy by Dr. Kaatz and his colleagues.

            Basically what was known before that, is there is about 20 cases of Celiac Disease in an adult  population of about 40,000 people in a county.  Not too shabby.  It is approximately the same as in Olmstead County [where Mayo Clinic resides], about 1 in 2000.  In Natrona County we found 32 new Celiacs who were double positive out of a population of 4,000.  Only 18 wanted to be biopsied, and 17 of those were biopsy-proven to have Celiac Disease.  This again shows that just under 1% of adults have Celiac Disease. 

Only half of them had GI symptoms, the most common being constipation.  Two who were positive had family members with Celiac Disease.  However there were no good predictors.  From questionnaires, we could not predict who might have Celiac Disease.  In those who were tested, It was just as common in men as in women.  So there is a lot of Celiac Disease in Wyoming, and I'd wager it's the same in Montana.

How Do We Find It?  There are a number of diagnostic methods.  Intestinal biopsies are still the Gold Standard and are maintained by many learned bodies that examine all of the evidence and say we still need a biopsy to prove this life-long disease with its life-long treatment.

Serological testing or blood testing we will discuss in some detail. The effect of a gluten-free diet is important for confirmation.  There are older, less accurate tests: X-rays, tests for deficiencies, D-Zylose tests, absorption and permeability testing--these are not accurate tests for diagnosing or detecting Celiac Disease.  Genetic testing we'll mention again.

            Damage to the intestine is the signature of Celiac Disease. However there is a spectrum of damage, from Classic to others that are much tougher to diagnosis on a biopsy, but they too are Celiac Disease.  Serologic or blood tests have the advantage of being a blood test.  It's an initial test that is available to any primary care doctor to send.  It's easy to exclude the diagnosis, so if you're a primary care doc seeing a patient you think may have Celiac Disease, and the test is negative, the chances are that the patient does not have Celiac Disease.  There are now standardized tests that are becoming available that will really help the doctor select which patients to refer to a specialist.  When I come to Montana, I realize that those specialists may be several hundred miles away.  That's a significant decision.

  Which blood tests should you use?  There are a number of serologic tests: gliadin, endomysial, Tissue Transglutaminase, and the measurement of total IGA.   Most Celiacs are positive for the Tissue Transglutaminase testing if they are on a regular diet. Once you put them on a gluten-free diet, most of them become negative.  So it's very important that the person be on a normal, gluten-containing diet before being tested. If you challenge patients for at least a month, most will become positive, and then they'll eventually become negative again [after returning to the GF diet]. 

            There are a few patients, maybe 4%, who will come up with a false positive number with the Tissue Transglutaminase test, so it's not a perfect test.  Gliadin testing I don't even do anymore or very rarely do.  I don't do it as a way of detecting new cases.  It is too inaccurate.  Thirty percent of the general population, who  don't have Celiac Disease, will come up positive.  So gliadin testing is not an accurate way of making the diagnosis.  Tissue Transglutaminase testing is pretty good, but not perfect; endomysial testing is again pretty good, but it's rather expensive.  One of the limitations of these blood tests is that some people have IGA deficiency and that's basically an immune protein that they just don't produce--so they can't come up positive on a test even if they have Celiac Disease.  Nor is it as good if there's only mild damage, and, most importantly, if the person has been on a gluten-free diet, it will make the test go negative. 

How about endoscopies?  Many people had an endoscopy before diagnosis, and while the doc was looking at their intestine up close and personal, he maybe was seeing the Celiac Disease.  A question I'm often asked by gastroenterologists:  Is it necessary to biopsy what looks like a normal duodeum?  There are some changes in somebody with Celiac Disease such as a fissuring of the intestine or more fissuring or cracks on the poles. However, you only see that about 50 or 60% of the time.  So just because a doc has looked at your intestine is not a good enough reason to say you don't have Celiac Disease.  Doctors have to take biopsies.

           A newer way of looking at your intestine is the capsule enteroscopy or the camera capsule. With our current way of looking, we only see the top little bit of the intestine, and the sampling we get by biopsy is limited to just that top 5% of the small intestine.  There really isn't a good correlation between the pathology, that's the damage seen on the biopsies, and the clinical state of the disease.  For example, someone with no symptoms at all can have a completely flat biopsy, whereas people with partial villus atrophy, partial flatness, can have severe symptoms.  Capsule endoscopy gives you a very magnified view of the lining.  It's immersed, which means it's not blown up with air, it's immersed under the intestinal juice.  The lining is not flattened with the compressed air that must be put in with a biopsy.  Potentially you can see the whole small intestine.  It's not particularly invasive.  It's probably the easiest GI test that gastroenterologists do--unless it gets stuck!  It's usually pretty painless.  You swallow the capsule, which contains two little button batteries.  As it goes through the intestine it has a little flashing light that takes pictures. It then transmits the pictures through the intestinal wall to a recorder that you wear on a belt or harness, and that is downloaded through the recorder to a computer.  The painful part of this test is not for the patient but for the gastroenterologist who will spend perhaps two hours gazing at these pictures on a screen, and can't DO anything.  Many of us went into gastroenterology because we could physically do things.  And here you are stuck--it's not even a decent video game!

What is a normal jejunal or small Intestine?  (Video Demonstration of a Capsule Endoscopy): In a normal intestine, you can see the deep pile carpet character somewhere in the middle of a healthy intestine.  In an unhealthy intestine, the lining looks quite different.  About a third of the way down, there are cracks on the folds, which means that the patient has at least a third of the small intestine involved with Celiac Disease.  This is a very sensitive test--about 90% of the time we can see the changes, so it's much more magnified than what we'd see with a regular scope.

  How much of the Intestine is typically involved?  We did a study of 40 people with untreated Celiac Disease and found there is no typical.  It varies from 1% to 60% of the intestine involved and the length does not seem to correlate with the severity of symptoms.  Hmmm!  Why do some people get bad symptoms and others not?  There may be some factors that do correlate, such as if you have bad damage at the top end, we expect that the damage will extend further down the small intestine.

  Prediction of Celiac Disease with the genetic type.  More than 95% of Celiacs carry the HLA type DQ2 or DQ8 , so if you don't have it you probably can't have Celiac Disease.  So no DQ2 or DQ8  no celiac risk.  However, 30% of the Caucasian population has this genetic type and the vast majority of those people with the celiac gene do not get Celiac Disease.

When should we use this genetic information?  I use it on people who are already on a gluten-free diet.  When people tell me that they have been on a gluten-free diet for six months and do not want to go back on a regular diet [the gluten challenge], we do the HLA type, and if they don't have the genes, I can highly predict that they don't have real Celiac Disease.   Perhaps they have some other intolerance or a wheat allergy.

            Sometimes it is useful in people who are at genetic risk but are blood test negative.  The group that genetic testing is probably most advantageous in are children with Down's syndrome, because you can rule out 80% of Down's syndrome children, telling them that they cannot get Celiac Disease.  It's quite useful for them if they are not able to verbalize their symptoms to you.

  Why not just try the Gluten-free diet?  This is one of the most frequent questions I'm asked by patients or family members: Why bother testing me--why not just go on the gluten-free diet and see if it gets better?

            Well, the diet is neither easy nor cheap, and we end up with unhappy, unsure patients much of the time.  Now if I have a patient who tells me that he's been on a totally gluten-free diet, he feels wonderful, symptoms have gone away, am I going to force him to eat gluten?  Not at all.  However, typically, I will also have patients who feel better but wonder if they must stay on this diet.  That's why I much prefer to test patients before they go on the diet.  The blood test and even the biopsy can become normal on a gluten-free diet.

            There is a placebo effect of dietary change that may not last more than two or three months; and one real effect among non-celiacs is food restriction.  If you have any gut disease and you stop eating, or reduce the amount of food you eat, whatever it is, your symptoms may lessen.  It is not because that food is damaging the intestine.  So there are reasons why a gluten-free diet may apparently work, but not for the right reasons.  Not having a definitive diagnosis is difficult for children, especially when they go to school.  It can delay making correct diagnoses, such as Crohn's disease, when they try out the gluten-free diet for three or four months and then start adding more foods that they put in their "do not eat' list.  Then I end up seeing a very emaciated patient and I must try to make the correct diagnosis after the fact.

What about a gluten challenge?  I do not like doing this.  I do not like making people sick.  It goes against the grain--literally.  The idea of a challenge is that the patient has to take in adequate gluten for long enough to develop gut lesions and make the patient sick.  Patients have to become symptomatic.

Usually you aim for four slices of whole wheat bread a day for four weeks.  As Celiacs, think about how sick you would get. There are some delayed responders, so some people may get no symptoms in four weeks.

I will do the blood testing; if it becomes positive I will do a biopsy, if it's negative I will wait up to six months before my patience wears out and then I'll go ahead and biopsy them.

            There is one case in the medical literature of somebody who was challenged for 14 years before the damage returned.

What is the treatment of Celiac Disease?  One celiac person called it gluten-free roulette.

A question more for physicians is: Who should we treat?  Obviously symptomatic patients and those who may not have symptoms, but have consequences of celiac disease, such as bone disease, anemia, or other consequences, and then possibly even those who have no symptoms:  I don't call them asymptomatic, I call them pre-symptomatic.  Those are people who have not yet got symptoms, but are treated possibly to reduce the risk of subsequent malignancy, to reduce the risk of bone disease, or other consequences or symptoms that could occur later in life.

The major triggers to Celiac Disease are certain grains.  The triticae are the cultivated grasses, with wheat, rye and barley the major ones.  So also are spelt, kamut and several others that are a cross between wheat and barley, called triticale.  All of those are basically part of this family of triticae and should be avoided by people with Celiac Disease.  There are the avenae, which are oats, and are a cousin, but not as tightly related as the three triticae.  Rice, corn, millet and sorghum of course are distant from and unconnected to the triticae.  Buckwheat is not even a grain and is totally unrelated.  The problem is that in a Co-op store it is often stored right next to the wheat flour and they share the same scoop.

The biggest source of contamination that I see are the commercial cereals.  Also eating out, communion wafers, lipstick, airborne flour or starch, and then soy sauces made with wheat.

  How much gluten is too much?  The threshold for damage in the gut is probably starting somewhere between 10 and 100 milligrams of gluten per day.  How much is 10 milligrams?  One ounce is 30 grams, or 30,000 milligrams, so 10 to 100 milligrams is very little indeed.  Symptoms are not a good indicator.  So you may eat 100 milligrams of gluten a day, get damage in your intestine, but you may not feel it at that time or within a day or two of eating it.  Some patients say, "But Doc, I eat it all the time and I don't get sick."  Yet they have come to me because of chronic diarrhea, bloating, belly pain, etc. They're not getting it, because it doesn't have that tight time association, and doesn't happen right after they eat gluten.

            On the other hand for some Celiacs, it's an immediate response that does happen within a couple of hours and they get deathly sick.  But not every Celiac has that response.

  What is the level when Tissue Transglutaminase antibodies becomes positive?  Probably somewhere around a gram of gluten a day.  You can eat half a slice of bread a day in order for that test to become positive.  That level is much higher than the level required for damage in the intestine.  Cheating--by somebody who deliberately cheats and eats a cookie or something with wheat in it once a month or more--are likely to have chronic injury and not heal their intestine.  Less often may result in some other consequences, such as a couple of days or a week of injury, but once a month or more of deliberate cheating is often enough to have chronic injury.  Of course, you can't separate the deliberate cheating from the carelessness, because often they will run together; so if someone tells me they are deliberately eating gluten once a month, they probably are also not being careful about minor ingredients.

            There is a high degree of variable sensitivity, so that some patients can get away with a little gluten and not get damage or symptoms.  Others cannot get away even with the tiniest amount. 

  What about the thresholds that are set for gluten content?  The new Codex Standards or Codex Alimentaricism International Standard of Food Composition, which will probably be finalized this year, are that anything labeled or called naturally gluten-free should have less than 20 parts per million [ppm].  That is well below the threshold that we need to worry about, so that's okay.

            Some countries have what are called Rendered Gluten-Free products.  Basically that's using wheat starch.  They try to extract as much of the protein out of it to take the gluten away from it.  Their standard for a product marked Rendered Gluten-Free will be 200 ppm.  This is kind of right on the threshold for some people, so those foods are not permitted to be imported into the US.  However, in other countries they are used as part of a so-called gluten-restricted diet.  In some patients that's enough to trigger symptoms.  One study done in Montreal, Canada, using rendered gluten-free products in children, found that half of them had to give up that diet and go back to a naturally gluten-free diet because of symptoms.

            But there is other data that suggests in places like Finland that people do as well on the rendered gluten-free diet as they do on the naturally gluten-free diet.  Currently the North American bodies, be they professional or support groups, want to stick to the naturally gluten-free label, not to encourage or permit rendered gluten-free, even though that is what the standard will be internationally.  So if you travel elsewhere, something that is rendered gluten-free may be marked gluten-free and will probably be up to 200 parts per million.

            Most of the studies used to generate these measures have been short-term studies. There is one 1-year study that is a randomized control trial that seemed to show a trend toward a response of getting symptoms at 50 milligrams a day, again giving us a sense that somewhere between that 10 and 100 milligrams of gluten a day is where the threshold for injury starts.

            Determining the safe threshold for gluten intake of any one patient is almost impossible.  I tell everyone with Celiac Disease, "You need to aim for a naturally gluten-free diet."  Most of the studies have been small with selective patients.  There is difficulty in measuring actual gluten intake, especially in European countries where they have rendered gluten-free products as well as naturally gluten-free products.  Also, there are a lot of dropouts.  I wonder if they were getting symptoms and therefore didn't finish the study.  We need to have much better outcome measurers, what are called biomarkers response to know, than what we have already.

  Who are "The Infamous French Girls Six?"  At the last International Celiac Meeting in Belfast, Northern Ireland, there were a couple of studies on analytical tests.  When you set a standard, you have to be able to verify that standard.  Government standards are totally worthless unless they are regulated!  Someone must actually police them.  There are now a couple of tests that will be pretty sensitive. One that is in development is sponsored by the European Union, and should cost about 15 Euros or about 17 - 18 US dollars.  It is meant for food manufacturers or for regulatory agencies rather than for individuals.

            There is also the presentation of what are called "The Infamous French Girls."  I call it "The Infamous French Girls Six."  There had been a series of French girls who were identified with Celiac Disease as children in the 1970's.  The gastroenterologist who looked after them told them they could go back on a regular diet after about the age of five or six.  Most of them did go on to a regular diet.  However, seventy percent of those who've lasted now into adulthood have villous atrophy.  Many have low-bone density, anemia, and common mild symptoms.  Those without villous atrophy had a very early age of diagnosis, about the age of one or younger, when it's really very hard to be absolutely certain of the diagnosis of Celiac Disease.  There are going to be more installments and it's not clear that tolerance is achievable in any patients.  I suspect that those 15% who still appear to tolerate gluten, may not have truly had Celiac Disease in the first place, since they were diagnosed at such a young age.   This story continues...  

  Does treatment require that the mucosa recovers completely?  What is the definition of recovery?  We don't even agree on the definition of damage!  And is recovery universal among treated Celiacs?  It is certainly not.  We have to wait longer in adults than in children. In adults I would wait a year to rebiopsy them, rather than in 6 months or 3 months; it's just too soon. Yet often a doctor will rebiopsy in 6 weeks or 12 weeks, see that the villi are no better and state that the person must not have celiac Disease, and recommend that he go back on a regular diet. 

            I don't rebiopsy everybody.  I rebiopsy those I think might be at risk for complications: those who are not compliant with the diet, or not likely to be compliant with the diet, those who continue to have symptoms.

all patients that we've diagnosed at an older age (over 50).  We need some good population data on recovery--we don't know when we look at a population what recovery means. 

There was one presentation at the International meeting from Finland that compared Finnish recovery with New York patients, and suggested that only 30-to-40% of New York patients had complete recovery.  At least in my patients, I expect 70-to-80% of complete healing of the intestine, if we wait long enough and they are on a strict enough gluten-free diet. There are few patients who do not heal completely.

Are there deficiencies in the gluten-free diet?  Generally, I would regard the gluten-free diet as being a perfectly healthy diet.  However, if we look at diet intake histories, they underestimate calculated means for calories, so some people underestimate how much they actually eat.  That's a problem for Celiacs who gain a lot of weight.  Also, calcium and folate intake may be low in treated Celiac patients.  If you eat very little fresh greens you may be deficient in folic acid.  Similarly calcium, if you're avoiding milk and dairy products for example you are getting very little calcium.  I have no hesitation in recommending calcium supplementation or multi-vitamins for patients with Celiac Disease.  I think it's probably a good idea.

And it is important in following patients that they be aware that their diet not just be gluten-free, it's got to be healthy and gluten-free.  We don't know what the impact of these deficiencies might be.  Cummings, who is a nutritionist from England, looked at the British gluten-free diet, and found that what the British eat is not very good, and the gluten-free version of it is even worse yet. So it is important that the diet be a healthy one albeit gluten-free.

What are the negative impacts of the gluten-free diet?  We should be aware that there are negative impacts.  For example, there is a negative impact on diet and on life-style.  A study from Roland Lee of New York estimated the impact on family, both men and women with Celiac Disease; a significant portion said it had a substantial impact on their family life, on travel, and on dining out.  However, I thought it rather remarkable that only a third of women with Celiac Disease felt it had a major impact on eating out.  That means that two-thirds did not.  Surprisingly, two-thirds felt it impacted their work place, because so many social events involve food.  So we should not completely ignore the potential negative impact of a gluten-free diet.

What about oats?  The Finnish oat study, which is now a little over five years of follow-up, used specially grown and tested oats, and gave patients 50 grams or a little under two ounces of oat product a day.  They used controls for biopsy and serologic testing.  The study showed that it appeared to be no different, whether you included oats or not, in that form, in the diet.

            There were Irish, Canadian and Danish studies that showed similar results.  However, so far I am a little conservative when it comes to oats.  Some oat samples may have wheat or barley contamination because of where they're grown, processed, milled or packaged.  There are shared sequences of glutamine repeats in the oats, and there are a few Celiacs, maybe 5 or 10%, who react against pure oats, and most of those studies excluded the severely ill patients.  So I don't want newly diagnosed patients to include oats in their diets.  There are some recent reports of oats affecting intolerant Celiacs from Norway.  So I say, "Not yet!"

            When they come out with good, safe, uncontaminated oats, and if the patient has already healed and become asymptomatic, I think it's reasonable to include a pure form of oats.  But there are a lot of if's and but's in there! I do think oats will be in the future of most people with Celiac Disease.

What about Lactose?  About half of the people with Celiac Disease are lactose intolerant at diagnosis.  That means they also can't digest the milk sugar in lactose, and become secondarily lactase deficient because they don't have the lactase enzyme, which is produced at the tips of the villi.  Most should become lactose tolerant in 6 to 12 months on a strict gluten-free diet, which means that they should be able to ingest some milk without getting symptoms.  I only restrict lactose intake in those who've got symptomatic lactose intolerance.  I do not make a blanket prohibition on lactose or dairy products, which are important sources of calcium. 

When restricted, I usually suggest to people that they try to reintroduce some lactose in six to twelve months to see how they do. 

What about monitoring the diet?  At the end of the first month, the symptoms should be better, by 3 to 6 months, deficiencies should be better, at 6 months serologic tests should start to drop or become negative, and at a year, if we rebiopsy, the biopsy should be near normal or normal.  Then I recommend a regular follow-up every year or two years, depending on the patient and their circumstances.

Healing:  If you biopsy someone who had Celiac Disease diagnosed as a child, his or her intestine should be perfectly and completely normal.  So much so, that I encourage my patients that once they've been out a year or more and they are as good as healed, and they feel completely better on their strict gluten-free diet, to stop thinking they have Celiac Disease.  Yes, they're Celiacs--but they no longer have a disease!   They should not think of themselves as deficient, or dysfunctional, or abnormal in any way.  They are perfectly normal, so long as they stay away from gluten.

What about non-responsive Celiac Disease?  It doesn't happen for everyone that they get completely better.  The most common reason for patients that I see who come to me with problems despite being on a gluten-free diet (#156) is the diet.  More than 50% of the people who think they're on a gluten-free diet, who believe they're on a gluten-free diet, have gluten in their system.

            The next most common reason for continued symptoms despite a gluten-free diet is lymphocytic colitis, a relatively rare inflammatory condition of the colon.  The colon doesn't look abnormal until you take biopsies.  Typically that has to be treated with some type of medication.  On the good side, it doesn't progress to anything else.  In some patients, the pancreas doesn't produce enough digestive juice, and need some enzymes to help them digest.  Some patients have excess bacteria growing in the intestine.  A few patients have truly Refractory Sprue, which is not a good thing.  True Refractory Sprue is a very serious illness that requires the attention of an expert to deal with it. 

What about complications with Celiac Disease?  We know that mortality is 2-fold greater with every age, primarily because of GI malignancies.  Osteoporosis, stunted growth, infertility, and chronic ill health are more common than in the general population.  Most of that is related to untreated or very late treated disease.  In the hips bone fractures that just happen to somebody standing up are called pseudo fractures.   It is a very painful process that heals completely on a gluten-free diet after a year.

            Lymphoma, or lymph gland cancer, is a very bad problem.  Mortality is quite high.  However, it is not something that most people with Celiac Disease should be worried about.  Yes, people with Celiac disease are much more prone to this cancer, but it's exceedingly rare.  In our Olmstead county in Minnesota there has been only one of these cancers in the whole population in 50 years.  So it is a very slight risk for people with treated Celiac Disease.  The time when Doctors think about it is in the first five years after diagnosis of somebody over the age of fifty.

What are some of the medical benefits of Celiac Disease?  It may be that diagnosed Celiac Disease protects people from obesity, high cholesterol, or high blood lipids, and perhaps reduces their heart disease risk.  What was remarkable from the Olmstead study follow-up was that not a single patient died of heart disease.  That's quite unusual, to see absence of death from heart disease in a population like that. There are similar results from a study in Cambridge, England.  So not all Celiac Disease is necessarily bad.

  What is the future for patients of Celiac Disease?  Better tests?  A preventive vaccine?  Nutritional strategy, such as not giving children solid food within the first four months of age?  Does prolonged breast feeding protect them?   Does gluten cause other disorders such as neurologic disorders?  What might Celiac Disease tell us about other diseases?  These questions are unanswered.  This is the one autoimmune disease where we know the environmental trigger. Maybe Celiac Disease can give us a view into what triggers other autoimmune diseases.  What role do genes and our interaction with our environment play? 

  Will there be an alternative to the Gluten-free diet?  Ten years ago I would have said there was no such possibility, but now I get calls from drug companies about every three or four months interested in having me come out and talk to their discovery group about Celiac Disease.  So yes, it's getting on the radar screen.

            Can we engineer a non-toxic wheat from genetically modified foods?  Possibly...  One US group gave up because it was so difficult, but a European group is trying now.  Can we block the autoimmune response?  

And finally, how would we test these alternative treatments?  We do have to be responsible, for this is not a disease to play around with, and the gluten-free diet is a safe and effective treatment, in spite of being awkward and restrictive.

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APPENDIX  A

Serologic Screening Study

An estimate of the prevalence of Celiac Disease in the United States. 

Principal investigators are KAROLY HORVATH, MD, PhD., and ALESSIO FASANO, MD

Recently, a blood test was developed to help identify people who may be at risk for celiac disease.  The test requires a sample of blood to be taken from a vein in the arm.  It the test is positive, it indicates that the person may have celiac disease and should undergo more definitive investigation to confirm the diagnosis.  This test has been widely used for several years in Europe.  It has become obvious that celiac disease is much more common in European countries than was previously realized.  As many as 1 in every 200 – 300 people tested have been found to have celiac disease.  Our preliminary studies based on the analysis of 2000 blood samples found that 1 in every 250 healthy Americans may have celiac disease. 

  The Serum Antibody Test:   The Serum Antibody Test:

“Based on the data, the prevalence of CD in Montana is:"

  1. FIRST DEGREE RELATIVES in Montana = "3.95% or  (2:51).

We recommended the biopsy to 3 further subjects that have AGA, IgA+ IgG.”

  2. SECOND DEGREE RELATIVES:  "We tested 23 second degree relatives’ samples. 16 out of 23 are relatives of biopsy proven celiac patients.  One out of 16 is EmA positive (prevalence: 6.2%)."

  3. CELIAC PATIENTS:  "We tested 41 celiac patients, 17 biopsy proved.  Two out of 17 were EmA positive; 1 was AGA, IgA + IgG positive."

  Data provided by Dr. Irené Berti, Horvath/Fasano Research Laboratory, University of Maryland Hospital. A serum antibody test of 150 patients was conducted during Dr. Fasano's Billings presentation, June  19TH, 1999, Billings Deaconess Hospital.  The above data, from the Fasano/Horvath lab, are of biopsy-proved patients only.  Blood test forms are available from Montana Celiac Society.  Over 225 Montanans have taken the serum antibody test as of 1-2001. 

         If wishing to participate, or for more information, contact:

Pediatric GI & Nutritional Laboratory   

Alessio Fasano

UMAB Bressler Research Building

655 West Baltimore Street, Room #10-047

Baltimore, Maryland  21201

Telephone: [410] 706-1997; FAX: [410] 706-0020

 

 

 

 

 

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APPENDIX B

SIGNS & SYMPTOMS OF CELIAC DISEASE

  THE FOLLOWING LIST IS AN OUTLINE OF SYMPTOMATIC POSSIBILITIES

SYSTEM: SIGNS & SYMPTOMS:
GENERAL 

Weight loss & generalized malnutrition

Edema & Ascites

Low Systolic blood pressure

Slight pyrexia (fever)

Nocturia (awakening at night to urinate)

 

Gastrointestinal System

Diarrhea, periodic constipation, vomiting, flatulence

Paralytic Ileus                                                                         

Abdominal (cramplike) pain

Enlarged liver, pruritis (itching)

Anorexia, excessive appetite

Glossitis

Stomatitis

Lactose intolerance, lactase deficiency 

Stomatitis 

Steatorrhea 

Abnormal bowel bacterial flora

Ulcerative colitis; volvulus (twisting of the bowel)

HEMATOPOIETIC SYSTEM
Anemia, Iron & Folic Acid deficiency

Deficiency of coagulation factors

Marked atrophy of the spleen

Pallor, headache, dizziness & dyspnea

MUSCULOSKELETAL SYSTEM               

Bone pain, generalized osteoporosis

Rickets, compression fractures

 Muscular weakness

Tetany

Parethesias

SKIN, HAIR & NAILS

Dry, scaly, hyperpigmented, itchy skin

Acne, Rosacea, Psoriasis, 

Eczema                                                                                                                                                            

Herpetiformis lesions

 Hair loss

Brittle and/or abnormal nails

Clubbing of fingers

Nervous System

Polyneuritis 

Myelopathy (disease of  spinal chord/bone marrow)

 Encephalomyeloradiculopathy (disease of brain)

Night Blindness, ataxia, demyelinization, seizures

ENDOCRINE, IMMUNOLOGIC 

Secondary hyperparathyroidism                                                                          

Hypopituitarism

Thyroid disorders, diabetes

Lymphoma, neoplasia (tumor formation)

Sarcoidosis (enlargement of lymph node

Pulmonary diseases, abscesses

Autoimmune, collagen diseases

Glomerulenephritis (renal IgA deposits)

PSYCHOLOGICAL SYSTEM
Nervousness, Depression, Anxiety
REPRODUCTIVE SYSTEM
Male: Decreased fertility, Impotence, bigonadism

Female: Menstrual disorders, delayed menarche, early menopause, infertility, miscarriages

PARTIAL COMPILATION from LIFELINE, CELIAC SPRUE ASSOCIATION/USA (CSA/USA 1995)  Box 31700  Omaha, Nebraska  68131-0700

REVISION by R. Jean Powell, MCS  2001 MONTANA CELIAC SOCIETY,  1019 SOUTH BOZEMAN #3  BOZEMAN, MONTANA 59715  

DEFICIENCY SYNDROMES, Compilation by R. Jean Powell

Osteomalacia:  Softening, weakening, and demineralization of the bones. In children, the condition is called rickets. Symptoms: pain in the bones, muscle weakness, tetany in the hands, feet, and throat. “Osteomalacia is usually caused by an insufficient amount of vitamin D in the diet, insufficient exposure to sunlight, or inadequate absorption of vitamin D from the intestine [malabsorption], which may be caused by a disorder such as Celiac Sprue...

Osteoporosis:  Loss of protein matrix tissue, from bone, causing it to become brittle and easily fractured. The difference between osteomalacia and osteoporosis lies between bones that bend and bones that break.

Beriberi:  Metabolic disorder caused by a lack of Thiamine [B1].  Essential for the metabolism of carbohydrates.  Without vitamin B1 the brain, nerves, and muscles, including heart, cannot function properly. 

Pellagra:  A nutritional disorder caused by a lack of Niacin resulting in dermatitis, diarrhea, and dementia. Symptoms: weakness, weight loss, lethargy, depression, irritability, itching & inflammation of skin exposed to sunlight, red, swollen tongue, confusion & memory loss.

Scurvy:  A disease caused by inadequate intake of Vitamin C.  Inadequate supplies of Vitamin C disturb the body’s normal production of collagen.  Hemorrhages may occur anywhere in the body, resulting in widespread bruising.  Bleeding from the gums and loosening of the teeth are common.  Bleeding into the muscles & joints also occurs in scurvy, causing pain.  Hemorrhages into and around the brain can occur. 

Anemia:

Vitamin B12:  Important in the production of genetic material of cells, in the production of red blood cells in bone marrow, in the utilization of folic acid and carbohydrates, and in the functioning of the nervous system.  Deficiency is almost always due to an inability of the intestine to absorb the vitamin.  Symptoms: a sore mouth & tongue, numbness & tingling in the limbs, depression, and loss of memory.

Iron: Poor absorption, sometimes due to Celiac Sprue.  Symptoms: fatigue, headaches, sore mouth and tongue, brittle nails, breathlessness, and pain in the center of the chest.

Hypokalemia:  A low level of potassium in the blood usually occurs as a result of a digestive tract disorder.  Symptoms:  Mild:  fatigue, drowsiness, dizziness, muscle weakness.  Severe:  abnormalities of heart rhythm and paralysis of the limbs.  Lead-boots feeling in the legs.

Vitamin A Deficiency:  Most often due to failure of the intestine to absorb.  Symptoms:  poor night vision; dry, inflamed eyes; dry, rough skin; loss of appetite, diarrhea, and lowered resistance to infection.

Riboflavin Deficiency: May cause chapped lips, soreness of the tongue & corners of the mouth, amblyopia & photophobia.    

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  APPENDIX CTesting for Celiac Disease

by R. Jean Powell

A specific procedure is required to accurately diagnose Celiac Disease: patients must be consuming gluten!   A frequent error, obtaining blood, stool, or biopsied samples for lab testing from a prospective patient who is already on a Gluten-Free diet, skews the results and happens more often than it should.

Text Box: NO DIETARY GLUTEN/GLIADINS =                                                            AN UNDIAGNOSED PATIENT

WHO iS IN  NEED OF TESTING

MUST BE 

CONSUMING GLUTEN/GLIADIN PROTEINS,

(wheat, rye and barley...).

 

1.    The blood test, the small intestinal biopsy, and the stool test measure gluten/gliadin antibodies in the blood or stool and show flattening of the villi in the small intestine.  Antibodies are produced and villi destruction occurs only while a Celiac patient is consuming gluten/gliadins (from     wheat, rye and barley).

  2.          A Celiac patient on the Gluten-Free diet stops producing elevated antibodies and the villi recover,             a process that begins immediately. This is a dynamic of simplicity and elegance. 

      For patients who have adopted the GF diet even a short time before testing, analysis will not give accurate results indicative of C.D.  The GF diet is functioning properly when antibody levels in the blood/stool return to normal and villi mend.

 Patient A:

Patient A has not consumed gluten for two months. His antibody tests will possibly fabricate an unreliable negative result, leaving patient a with no genuine diagnosis. This can cause complications with medical insurance and medical care.  Patients have reported that such false negative results convinced their health care providers that they were "cured" or not gluten intolerant at all, and were urged to return to a normal diet.  Several years later, that decision can have dire consequences for patients with C.D.

  Patient B:

Patient B has not yet adopted the GF diet.  His tests will in all probability be accurate, showing elevated antibodies and villi destruction.  Patient B receives a correct diagnosis, and then is placed on the Gluten-Free diet.  Medical and insurance complications are avoided.

  Patient A, whose health and sense of well-being had improved significantly on the GF diet, must now make one of two painful choices:

  Choice #1: To undertake the gluten-challenge by re-introducing gluten into his diet until symptoms reappear; or for as long as six months, whichever comes first.  Difficult for patient and doctor.

  Choice #2:  To decide not to take the gluten-challenge, and never receive a definitive diagnosis, affecting medical care and insurance acceptance.

Dr. Joseph Murray:

    Question:  

    Can you touch on the importance of being tested BEFORE going on the Gluten-Free diet?

    Answer: 

"Difficulties occur when the patient goes to a gastroenterologist after going on the GF diet.  At best, you will be facing a Gluten-Challenge, which may take some time to define, and may make you...really sick.  I’d say, about half of the patients who come to me in that situation cannot tolerate taking a gluten challenge.” J.M.

     Celiac Disease tests are accurate only if the patient is consuming gluten/gliadins.  The patient armed with this knowledge won't submit to a test whose results will be inaccurate and therefore useless--or even harmful.

 

 

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Montana Celiac Society: 1019 South Bozeman, #3 Bozeman, Montana 5971

 A LIFESAVER