Testing for Non-Celiac Gluten Intolerance

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Testing for Non-Celiac Gluten Intolerance

• Dr. Stephen Wangen
• Founder, IBS Treatment Center
• www.IBSTreatmentCenter.com

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What Keeps Me Awake At Night
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• What is wanted is not the will to believe, but
  the wish to find out, which is the exact
  opposite.
• Bertrand Russell (1872-1970)
• Sceptical Essays, 1928

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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.

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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.

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What Is Villous Atrophy?

• Villous atrophy is damage to the surface of the
  small intestine.
• This damage is a sign of gluten intolerance.

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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.

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Prevalence

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

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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.

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How and Why Does This Happen?

• First we must understand and define celiac
  disease in order to put this issue into the
  proper perspective.

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Celiac Disease and Villous Atrophy

• Celiac disease is defined by villous atrophy.
• Without villous atrophy, you cant have celiac
  disease.
• But villous atrophy must be put into its proper
  context

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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?

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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

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• 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)

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• 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

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• 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

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• Chromosomal defects
• Down syndrome
•  
• Miscellaneous
• Fatigue
• Anemia
• Iron deficiency
• Vitamin B12 deficiency (pernicious anemia)
• Vitamin K deficiency
• Folate deficiency
• Impotency
• Raynauds
• Eosinophils elevated (in blood test)
• Cystic fibrosis
• Pulmonary hemosiderosis
• Vasculitis

• Respiratory system
• Wheezing
• Sinusitis, chronic
• Shortness of breath
• Asthma
•  
• Womens health
• Irregular cycle
• Infertility (also male infertility)
• Delayed menarche
• Premature menopause
• Spontaneous abortion/miscarriage
• Head
• Headaches
• Migraines
• Alopecia (hair loss)

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• Autoimmune disorders
• Addisons 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-Hodgkins lymphoma

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Over 130 Problems!

• We know that many signs and symptoms can be found
  associated with gluten intolerance and celiac
  disease.

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Villous Atrophy Is Only One of These.

• Villous atrophy is only one possible end product
  of gluten intolerance.
• Celiac disease villous atrophy.

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What If You Dont 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.

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

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Gluten Intolerance
Celiac Disease
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Celiac Disease
Gluten Intolerance
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How Do We Know This?

• People tell us
• Clinical results tell us
• Blood tests tell us
• Medical Studies tell us

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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).
• Thats 14,200 per person, per year.

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What do the lab results look like for non-celiac
gluten intolerance?
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Negative Celiac, Positive Gluten Intolerance

• Tissue Transglutaminase antibody negative and
• Biopsy negative
• Gliadin antibody positive (IgA or IgG)
• Total IgA normal

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Some Studies on Non-Celiac Gluten Intolerance
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Small-bowel mucosal inflammation in reticulin or
gliadin antibody-positive patients without
villous atrophy. Scandinavian Journal of
Gastroenterology, 33, 944949. 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.

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Intolerance to cereals is not specific for
coeliac disease.Scand J Gastroenterol. 2000
Sep35(9)942-6. Kaukinen K, et al.

• Allergy to cereals other than celiac disease
  should be considered even in adults.

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Celiac disease without villous atrophy Revision
of criteria called for. Digestive Diseases and
Sciences, 46, 879887. 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.

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Common Blood Tests for Non-Celiac Gluten
Intolerance

• Gliadin antibodies
• Gliadin IgA
• Gliadin IgG

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• 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

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Gliadin Antibodies

• Not predictive of celiac disease.
• A great assessment of an immune reaction to
  gluten.
• Therefore a great assessment of gluten
  intolerance.

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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.

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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.

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• Emerging new clinical patterns in the
  presentation of celiac disease. Arch Pediatr
  Adolesc Med. 2008 Feb162(2)164-8. 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
  2003demonstrated that patients with celiac
  disease usually do not present with classic
  symptoms they are more likely to be
  asymptomatic

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Some Studies on Signs and Symptoms Associated
with Non-Celiac Gluten Intolerance
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Dietary treatment of gluten neuropathy. Muscle
Nerve. 2006 Dec34(6)762-6. 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.

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Myopathy associated with gluten sensitivity.
Muscle Nerve. 2007 Apr35(4)443-50.
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.

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Gluten sensitivity masquerading as systemic lupus
erythematosus. Ann Rheum Dis. 2004
Nov63(11)1501-3. 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 treatmentThe
  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.

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Dietary treatment of gluten ataxia. J Neurol
Neurosurg Psychiatry. 2003 Sep74(9)1221-4.
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.

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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 www.IBSTreatmentCenter.com for more info).
  

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A Few Studies on IgG Food Antibodies (other than
gluten)
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The clinical significance of food specific
IgE/IgG4 in food specific atopic dermatitis.
Pediatric Allergy and Immunology, 18(1), 6370.
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.

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Food-specific IgG4 antibody-guided exclusion diet
improves symptoms and rectal compliance in
irritable bowel syndrome. Scandinavian Journal of
Gastroenterology, 40, 800807. 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.

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Food-specific serum IgG4 and IgE titers to common
food antigens in irritable bowel syndrome.
American Journal of Gastroenterology, 100,
15501557. 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.

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Food elimination based on IgG antibodies in
irritable bowel syndrome a randomised controlled
trial. Gut. 2004 Oct53(10)1459-64. 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).

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The therapeutic effects of eliminating allergic
foods according to food-specific IgG antibodies
in irritable bowel syndrome. Zhonghua Nei Ke Za
Zhi. 2007 Aug46(8)641-3. 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.

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IgG and IgE Antibody Testing
IgG gray bar, IgE black bar
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IgG gray bar, IgE black bar
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You Cant Find What You Dont Look For
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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.

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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.

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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.

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• Lots more information about the
• Ecosystem of the digestive tract and
• Food allergy testing
• in The Irritable Bowel Syndrome Solution
• by Dr. Stephen Wangen

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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 dont yet
  know how to measure.
• So if the patient says that they cant eat
  gluten, but the lab work doesnt support it, then
  I still believe the patient!

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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.

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Due Out Fall 2008
The End!