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Testing for Non-Celiac Gluten Intolerance

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Presentation on theme: "Testing for Non-Celiac Gluten Intolerance"— Presentation transcript:

1 Testing for Non-Celiac Gluten Intolerance
Dr. Stephen Wangen Founder, IBS Treatment Center



4 What Keeps Me Awake At Night

5 What is wanted is not the will to believe, but the wish to find out, which is the exact opposite. Bertrand Russell ( ) Sceptical Essays, 1928

6 What Is Gluten? A protein found in wheat, barley, rye, and several other grains. Reactions to gluten are common and can cause many different problems. The most well known is celiac disease.

7 Gluten Intolerance and Celiac Disease
Celiac Disease is a very specific type of damage done to the digestive tract resulting from a gluten intolerance. This damage is the result of an autoimmune reaction that results in villous atrophy.

8 What Is Villous Atrophy?
Villous atrophy is damage to the surface of the small intestine. This damage is a sign of gluten intolerance. As we all know, villous atrophy is…. I’d love to get into the blood tests, but we don’t have time for that. They are fully discussed in my upcoming book on gluten intolerance.

9 Diagnosing Celiac Disease
Celiac disease is diagnosed by measuring the damage in the digestive tract by either a: Biopsy of the small intestine And/or Blood test called tissue transglutaminase antibody.

10 Prevalence Nearly 3 million people in the United States have celiac disease. But many more are gluten intolerant.

11 Gluten Intolerance Does Not Have to Mean Celiac Disease.
Many people know or suspect that there exist non-celiac forms of gluten intolerance. Patients test negative on blood work and biopsy for celiac disease, yet they know that wheat and gluten trigger their symptoms.

12 How and Why Does This Happen?
First we must understand and define celiac disease in order to put this issue into the proper perspective.

13 Celiac Disease and Villous Atrophy
Celiac disease is defined by villous atrophy. Without villous atrophy, you can’t have celiac disease. But villous atrophy must be put into its proper context

14 Other Signs and Symptoms Associated With Celiac Disease and Gluten Intolerance
What are all of the signs and symptoms associated with celiac disease and gluten intolerance?

15 Signs and Symptoms Associated with Gluten Intolerance
Digestive Diarrhea Constipation Abdominal pain Cramping Dyspepsia Gas Bloating Steatorrhea (fatty stools) Encopresis Enamel defects in teeth Heartburn Gastroparesis GERD Reflux IBS (irritable bowel syndrome) Esophagitis Eosinophilic gastroenteritis Eosinophilic esophagitis Canker sores Apthous ulcers These next several slides are the long list of problems associated with gluten intolerance. I apologize if they are too small to read, but reading them isn’t really the point that I want to make. What I want you to notice is that villous atrophy is on this list, but it’s only one of over a hundred problems.

16 Vomiting Nausea Intestinal bleeding Liver enzymes, elevated (ALT, ALK, ALP) Liver disease Pancreatitis Primary biliary cirrhosis Primary sclerosing cholangitis Colon cancer Lactose intolerance Fructose intolerance Occult blood in stool Hepatitis, autoimmune Hepatic steatosis Hepatic t-cell lymphoma Pancreatic exocrine function may be impaired Villous atrophy (celiac disease)

17 Skin Acne Eczema Dermatitis Dermatitis herpetiformis Dry skin Follicular keratosis Hives Rashes Itchiness Welts Redness Dark circles under eyes Physical well-being Fatigue Weight loss Weight gain Poor endurance Inability to gain weight Chronic fatigue Failure to thrive Short stature Emotional Anxiety Irritability Depression Up and downs

18 Mind/neurological Autism ADHD Difficulty concentrating Cerebellar atrophy Mental fog Brain white-matter lesions Insomnia/difficulty sleeping Schizophrenia Ataxia/difficulty with balance Epilepsy (with or without brain calcifications) Multifocal axonal polyneuropathy Neuropathy, peripheral (numbness or tingling of hands or feet) Musculoskeletal Arthritis Fibromyalgia Rheumatoid arthritis Muscle aches Joint pain Osteoporosis Osteopenia Osteomalacia Polymyositis Dental enamel defects Loss of strength Short stature MS (multiple sclerosis) Myasthenia gravis

19 Chromosomal defects Down syndrome Miscellaneous Fatigue Anemia Iron deficiency Vitamin B12 deficiency (pernicious anemia) Vitamin K deficiency Folate deficiency Impotency Raynaud’s Eosinophils elevated (in blood test) Cystic fibrosis Pulmonary hemosiderosis Vasculitis Respiratory system Wheezing Sinusitis, chronic Shortness of breath Asthma Women’s health Irregular cycle Infertility (also male infertility) Delayed menarche Premature menopause Spontaneous abortion/miscarriage Head Headaches Migraines Alopecia (hair loss)

20 Autoimmune disorders Addison’s disease Autoimmune chronic hepatitis Alopecia areata Diabetes, type 1 Graves disease Hyperparathyroidism, secondary Hypoparathyroidism, idiopathic autoimmune Lupus (SLE) Myasthenia gravis Sarcoidosis Scleroderma Sjogrens syndrome Hypothyroidism Villous atrophy Thyroiditis ITP (idiopathic thrombocytopenic purpurea) Malignancies Small bowel adenocarcinoma Esophageal and oro-pharyngeal carcinoma Melanoma Non-Hodgkin’s lymphoma

21 Over 130 Problems! We know that many signs and symptoms can be found associated with gluten intolerance and celiac disease.

22 Villous Atrophy Is Only One of These.
Villous atrophy is only one possible end product of gluten intolerance. Celiac disease = villous atrophy. Villous atrophy is simply one possible result of gluten intolerance. (Go Back to that slide.) But you don’t have to have villous atrophy to have a gluten intolerance. Many people experience one or more of these problems due to gluten intolerance, but they don’t have villous atrophy. Villous atrophy is just one of many signs and symptoms of gluten intolerance. And thus, celiac disease is just one form of gluten intolerance.

23 What If You Don’t Have Villous Atrophy?
Most of these are also signs and symptoms that can be associated with gluten intolerance even when villous atrophy is not present.

24 Celiac disease (villous atrophy) is a gluten intolerance, but
Gluten intolerance is not always celiac disease (villous atrophy).

25 Gluten Intolerance Celiac Disease
We like to talk about villous atrophy just being the tip of the Celiac disease iceberg. I believe that it is only a small part of the even larger gluten intolerance iceberg. Which is only a small part of the food allergy iceberg.

26 Celiac Disease Gluten Intolerance

27 How Do We Know This? People tell us Clinical results tell us
Blood tests tell us Medical Studies tell us I’m a big fan of common sense. I believe my patients. They know a lot. The emphasis in the celiac world seems to be that the testing is faulty and that diagnoses are being missed because they aren’t being done right. Testing will never be perfect and there are certainly issues here (also discussed in my book), but the larger problem, in my opinion, is that our focus is too narrow. How many of you know someone who is gluten intolerant but not celiac? And I see the same thing in my clinic every day. Over and over I’ve seen patients who have had the blood tests and the biopsy, and they are NOT celiac. But they obviously feel much better when they avoid gluten. And I’ve heard the rebuttals that the testing just needs to be reinterpretted, but we’re talking about thousands and likely millions of people. Too many to chalk up to error.

28 The Free Market Tells Us
The University of Chicago Celiac Disease Center states that 97% of celiacs have not been diagnosed. (Only about 70,000 dx.) The market for gluten free products is now known to be over $1 billion per year (USDA estimates $1.7 bill by 2010). That’s $14,200 per person, per year.

29 What do the lab results look like for non-celiac gluten intolerance?

30 Negative Celiac, Positive Gluten Intolerance
Tissue Transglutaminase antibody negative and Biopsy negative Gliadin antibody positive (IgA or IgG) Total IgA normal

31 Some Studies on Non-Celiac Gluten Intolerance

32 Small-bowel mucosal inflammation in reticulin or gliadin antibody-positive patients without villous atrophy. Scandinavian Journal of Gastroenterology, 33, 944–949. Kaukinen, K., et al. (1998). “CONCLUSIONS: IgA-class … antigliadin antibody-positive patients with normal small-bowel mucosal morphology … implies that they may be gluten-sensitive.”

33 Intolerance to cereals is not specific for coeliac disease
Intolerance to cereals is not specific for coeliac disease. Scand J Gastroenterol Sep;35(9): Kaukinen K, et al. “Allergy to cereals [other than celiac disease] should be considered even in adults.”

34 Celiac disease without villous atrophy: Revision of criteria called for. Digestive Diseases and Sciences, 46, 879–887. Kaukinen, K., et al. (2001). “10 adults suspected to have celiac disease, but evincing only minor mucosal inflammation … showed a clinical, histological, and serological recovery on (a gluten free) diet.”

35 Common Blood Tests for Non-Celiac Gluten Intolerance
Gliadin antibodies Gliadin IgA Gliadin IgG Normal healthy people do not have gliadin antibodies.

36 Discovery is to see what everyone else has seen and to think what no one else has thought. Albert Szent Gyorgyi 1937 Nobel Prize in Medicine

37 Gliadin Antibodies Not predictive of celiac disease.
A great assessment of an immune reaction to gluten. Therefore a great assessment of gluten intolerance. Gliadin antibodies have gotten a bad rap because they are not an accurate assessment of celiac disease. Of course not, celiac disease is villous atrophy, only one consequence of a gluten reaction. But gliadin antibodies assess whether or not someone is forming an immune reaction to gluten and is therefore gluten intolerant. Healthy people don’t have gliadin antibodies. Ironically, this test is run by most doctors, but ignored once the celiac testing is done. And it is also used in many screening studies for celiac disease.

38 Commonly Used as a Screening Test for Celiac Disease
Numerous studies have used gliadin antibodies to begin screening people for celiac disease, including most studies on the prevalence of celiac disease. Many studies on signs and symptoms associated with gluten intolerance are based on gliadin antibodies and not celiac disease.

39 Non-Celiac Gluten Intolerance is Not Less Severe Than Celiac Disease
Nor is there any evidence that celiac disease is the end stage of gluten intolerance.

40 Emerging new clinical patterns in the presentation of celiac disease
Emerging new clinical patterns in the presentation of celiac disease. Arch Pediatr Adolesc Med Feb;162(2): Telega G, Bennet TR, Werlin S [A review of] the medical records of all patients diagnosed with celiac disease at the Children's Hospital of Wisconsin between 1986 and 2003…[demonstrated that patients] with celiac disease usually do not present with classic symptoms; they are more likely to be asymptomatic…”

41 Some Studies on Signs and Symptoms Associated with Non-Celiac Gluten Intolerance

42 Dietary treatment of gluten neuropathy. Muscle Nerve
Dietary treatment of gluten neuropathy. Muscle Nerve Dec;34(6): Hadjivassiliou M, et al. “We studied the effect of a gluten-free diet in patients with idiopathic sensorimotor axonal neuropathy and circulating antigliadin antibodies. A total of 35 patients participated in the study, with 25 patients going on the diet and 10 not doing so. There was a significant difference … with evidence of improvement in the [treatment] group and deterioration in the control group.”

43 Myopathy associated with gluten sensitivity. Muscle Nerve
Myopathy associated with gluten sensitivity. Muscle Nerve Apr;35(4): Hadjivassiliou M, et al.   “Among seven patients not on immunosuppressive treatment, four showed clinical improvement of the myopathy with a gluten-free diet. The myopathy progressed in one patient who refused the gluten-free diet. Myopathy may be another manifestation of gluten sensitivity and is likely to have an immune-mediated pathogenesis.”

44 Gluten sensitivity masquerading as systemic lupus erythematosus
Gluten sensitivity masquerading as systemic lupus erythematosus. Ann Rheum Dis Nov;63(11): Hadjivassiliou M, Sanders DS, Grünewald RA, Akil M. “Three patients are described whose original presentation and immunological profile led to the erroneous diagnosis of systemic lupus erythematosus. The correct diagnosis of gluten sensitivity was made after years of treatment…The presence of an enteropathy is no longer a prerequisite for the diagnosis of gluten sensitivity, which can solely present with extraintestinal symptoms and signs. Knowledge of the diverse manifestations of gluten sensitivity is essential in avoiding such misdiagnosis.”

45 Dietary treatment of gluten ataxia. J Neurol Neurosurg Psychiatry
Dietary treatment of gluten ataxia. J Neurol Neurosurg Psychiatry Sep;74(9): Hadjivassiliou M, Davies-Jones GA, Sanders DS, Grünewald RA. “Gluten ataxia is an immune mediated disease, part of the spectrum of gluten sensitivity, and accounts for up to 40% of cases of idiopathic sporadic ataxia. Twenty six patients (treatment group) adhered to the gluten-free diet and had evidence of elimination of antigliadin antibodies by one year. CONCLUSIONS: Gluten ataxia responds to a strict gluten-free diet even in the absence of an enteropathy.”

46 Antibodies Against Foods Other Than Gluten
In the same way, you can also test for antibodies to wheat, barley, rye, spelt, etc. Typically IgG antibodies. If gliadin antibodies are elevated, these will also be elevated. (Visit for more info). This is the same technology that is used for the celiac and gliadin testing, ELISA. Though very few labs in the country are doing this and doing it well.

47 A Few Studies on IgG Food Antibodies (other than gluten)

48 The clinical significance of food specific IgE/IgG4 in food specific atopic dermatitis. Pediatric Allergy and Immunology, 18(1), 63–70. Noh, G., et al. (2007). “Specific IgE and IgG4 concentration were measured ... Double blinded placebo controlled food challenge test (DBPCFC) was performed. Mean IgE/IgG4 levels in DBPCFC (+) subjects is higher than those in DBPCFC (-) subjects in all food items studied. Allergen-specific IgE/IgG4 may provide one of the clues to understand the mechanism of food allergy in atopic dermatitis.”

49 Food-specific IgG4 antibody-guided exclusion diet improves symptoms and rectal compliance in irritable bowel syndrome. Scandinavian Journal of Gastroenterology, 40, 800–807. Zars, S., et al. (2005). “IgG4 antibodies to common food antigens are elevated in IBS. The aim of this article was to evaluate the effect of exclusion diet based on IgG4 titres… CONCLUSIONS: Food-specific IgG4 antibody-guided exclusion diet improves symptoms in IBS and is associated with an improvement in rectal compliance.”

50 Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome. American Journal of Gastroenterology, 100, 1550–1557. Zars, S., et al. (2005). “No significant difference in IgE titers was observed between IBS and controls. Serum IgG4 antibodies to common foods like wheat, beef, pork, and lamb are elevated in IBS patients. In keeping with the observation in other atopic conditions, this finding suggests the possibility of a similar pathophysiological role for IgG4 antibodies in IBS.”

51 Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut Oct;53(10): Atkinson W, et al. “150 outpatients with IBS were randomised to receive, for three months, either a diet excluding all foods to which they had raised IgG antibodies (enzyme linked immunosorbant assay test) or a sham diet excluding the same number of foods but not those to which they had antibodies. CONCLUSION: Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research. (The compliant patients experienced significant benefit).”

52 The therapeutic effects of eliminating allergic foods according to food-specific IgG antibodies in irritable bowel syndrome. Zhonghua Nei Ke Za Zhi Aug;46(8): Yang CM, Li YQ. “CONCLUSIONS: Abnormal immune reactions mediated by IgG antibodies coexisted in patients with IBS. It is of great significance in treating IBS by eliminating the allergic foods according to the serum level of food-specific IgG antibodies.”

53 IgG and IgE Antibody Testing
IgG = gray bar, IgE = black bar

54 IgG = gray bar, IgE = black bar

55 You Can’t Find What You Don’t Look For

56 Non-gluten Wheat Reactions
It is also possible to react to wheat and other grains without reacting to gluten. There are many other proteins in these foods. Antibody tests to wheat, barley, rye, spelt, etc can be positive when the gliadin test is negative.

57 Non-immune Reactions to Wheat
The ecosystem of the digestive tract plays an important role in how food is digested. Problems here can and do create significant digestive and skin problems. Bacterial and yeast imbalances can simulate a gluten or wheat intolerance. The “intolerance” resolves once the imbalance has been treated. I have seen instances where the patient had such a tremendous bacterial imbalance that every time they ate carbs (wheat), they had digestive symptoms that they attributed to a wheat or gluten intolerance. However, once the bacterial or yeast problem was treated, their symptoms resolved. These are cases where the food antibody testing was negative.

58 Stool Testing Thorough stool testing can measure most of the organisms in the digestive tract. Good bacteria: acidophilus and bifidobacterium Bad bacteria: Klebsiella, Psuedomonas, Citrobacter, Aeromonas, many others. Yeast/Candida Parasites. I always do this in conjunction with food antibody testing. Many people have problems in both areas. Very few labs or doctors who do this. Most of the bacteria you’ve never even heard of. Many people with gluten intolerance don’t improve after avoiding gluten the way they would expect to because they also have bacterial problems or other food allergens.

59 Lots more information about the
Ecosystem of the digestive tract and Food allergy testing in “The Irritable Bowel Syndrome Solution” by Dr. Stephen Wangen If you want to learn more about this topic, come to my lecture this afternoon at 3:15, Probiotics and the Ecosystem in the Digestive Tract.

60 Other Gluten and Wheat Reactions
It would be a mistake to assume that we know everything. Lab tests are just tools. Therefore there are likely other types of reactions to gluten or wheat that we don’t yet know how to measure. So if the patient says that they can’t eat gluten, but the lab work doesn’t support it, then I still believe the patient! Possible enzyme deficiencies. Lactose and fructose can’t be the only ones. And It’s not like you have to eat gluten to be healthy.

61 Summary Gliadin antibodies indicate gluten intolerance, even in the absence of celiac disease. Gluten intolerance can potentially cause a large number health problems. Gluten intolerance is likely far more common than celiac disease. I’d estimate that at about 10% of the population is gluten intolerant, though that could be low. That means nearly 30 million people. I do not believe that celiac disease (villous atrophy) is an end stage of gluten intolerance. There is no evidence to prove that. I also do not believe that celiac disease (villous atrophy) is necessarily a bigger threat to a person’s health than other types of gluten intolerance. Either one can be asymptomatic or very ill. Quote some stats on this. How does this relate to genetic testing for celiac disease? Are all of those people who are HLADQ2 and DQ8 actually gluten intolerant even though most don’t have celiac disease?

62 Due Out Fall 2008 The End!

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