3/18/2015

Objectives

THE GLUTEN
CONUNDRUM

Define the currently acknowledged gluten-related

disorders
Differentiate between gluten-related disorders in terms of

symptoms, current diagnostic methods, and treatment.

Janelle Smith, RD
Medical Advisory Board Member & Ask the Dietitian
Celiac Disease Foundation

Recommend appropriate medical nutrition therapy for

gluten-related disorders
Be familiar with co-occurring disorders which may impact

Chapter President, CDF Southern California Chapter

Gluten-related disorders
All conditions related to gluten[including] gluten ataxia,

dermatitis herpetiformis, non-celiac gluten sensitivity, and

celiac disease
- The Oslo definitions for coeliac
disease and related terms. Gut. (2013)

patients with gluten-related disorders

Gluten: definition in celiac disease

Protein component of wheat, rye, barley
Alcohol-soluble prolamins, complex polypeptides
Make up half of protein in mature grain

Wheat: gliadins and glutenins

Rye: secalins

Terms not recommended: gluten intolerance, gluten

Barley: hordeins

allergy, gluten sensitivity (w/out non-celiac)

Prolamins in other grains are genetically distinct and are not

involved in the immune response of celiac disease

Celiac Disease: definition

Chronic small intestinal immune-mediated enteropathy

precipitated by exposure to dietary gluten in genetically

predisposed individuals Oslo definition
For most individuals (but not all), enteropathy resolves on

gluten-free diet
1% Caucasians
0.71% Americans
8% type 1 DM
10% 1st degree relatives
83% undiagnosed in 2010
Source: Cureceliacdisease.org
(University of Chicago Celiac Disease Center, published Dec. 28, 2012)

(NHANES 2009-2010)

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Celiac Disease: symptoms

Over 200 identified the great pretender
Adults

Children

Iron-deficiency anemia (unresponsive

to iron therapy)

Failure to thrive

Chronic diarrhea (30% adults) or

constipation

Chronic diarrhea or constipation

Elevated serum transaminases

Nausea, emesis

Recurring abdominal bloating & pain

Recurring abdominal bloating & pain

Mouth sores (aphthous ulcers)

Delayed puberty

Unexplained infertility; recurrent

miscarriage

Short stature
Non-response to Hep B vaccine

Early-onset osteopenia/osteoporosis

Dental enamel defects

Peripheral neuropathy

Irritability, attention deficit, anxiety,

depression

Celiac Disease: diagnosis

Presence of specific antibodies (gluten-containing diet):
anti-tissue transglutaminase antibodies (TTG, a-tTG)
endomysial antibodies (EMA)
deamidated antigliadin antibodies (DGP)
Intestinal biopsy via EGD: 4-6 samples, including 1 from

duodenal bulb (gluten-containing diet):

Increased intraepithelial lymphocyte count in small intestine, most

often >25/100 cells

Histological changes: villous atrophy, crypt hyperplasia

DQ2 and/or DQ8 positive genes

positive gene test is not diagnostic; negative gene test excludes CD
Positive response to gluten-free diet

Dermatitis Herpetiformis: definition

Dermatitis Herpetiformis: diagnosis

Skin manifestation of CD

Punch biopsy of skin adjacent to blisters show deposits of

Itchy blisters, especially on elbows, buttocks and knees

Villous atrophy in 95% with multiple biopsies

IgA
No intestinal biopsy needed, but may be informative

Often asymptomatic re: GI symptoms

Effects 11.2 in 100,000 in US (approx. 15-25% of those

with CD)
Blisters resolve on GFD. Can be treated with Dapsone to

relieve symptoms

Source: Dartmouth Medical School

Gluten Ataxia: definition

Gluten Ataxia: symptoms

Idiopathic sporadic ataxia and positive serum antigliadin

Ataxia = uncoordinated movement, gait, speech, fine

antibodies (AGA), even in absence of duodenal

enteropathy Oslo definition
May occur because of CD or in absence of CD
Causes damage to cerebellum: 60% of cases show

cerebellar atrophy on MRI

motor control
Improvement in symptoms from gluten-free diet (may or

may not resolve completely)

Neurologic symptoms typically longer-lasting and more

sensitive to small amounts of gluten

Unknown prevalence. Ataxia effects 8.4 in 100,000

Americans. Estimates of 11-42% of those with idiopathic

ataxia

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Gluten Ataxia: diagnosis

Wheat Allergy: definition

Done by neurologist

IgE-mediated immune response to proteins in wheat

No other known cause of ataxia

Positive serum anti-gliadin antibodies (IgA or IgG)
Deposits of IgA TTG2 antibodies in small intestine
Possibly serum IgA TTG6 antibodies further research

needed
May be HLA-DQ2 positive (approx. 72%)
May or may not have villous atrophy, positive serum TTG

or EMA antibodies -> celiac disease

Often transient (outgrown): mean 6.5 years

Occurs in minutes a couple hours
Bakers asthma & rhinitis respiratory response
4.2 12.5% occupational bakers
Allergens: alpha-amylase inhibitors, germ agglutinin, peroxidase, lipid
transfer proteins
Symptoms: asthma/wheezing, itching nose, sneezing
Wheat allergy ingestion response
0.5 3% Americans (children adults)
Allergens: gliadins
Symptoms: atopic dermatitis, hives, gastrointestinal symptoms
Wheat-dependent exercise-induced anaphylaxis

Wheat Allergy: diagnosis

Non-Celiac Gluten Sensitivity: definition

Skin prick test + serum IgE antibodies to wheat

One or more of a variety of immunological,

Together only 75% sensitive, often d/t cross-reactivity with

grass pollens
Oral food challenge is ideal
IgG antibodies not sensitive or specific to wheat allergy

Non-Celiac Gluten Sensitivity: symptoms

20-40% continue to have symptoms on GFD
Abdominal bloating, pain
Mouth sores
Peripheral neuropathy
Fatigue, lethargy
brain fog

morphological, or symptomatic manifestations that are

precipitated by the ingestion of gluten in individuals in
whom CD has been excluded Oslo definition
Exact culprit unknown
FODMAPs?
Wheat alpha-amylase/trypsin inhibitors (ATIs)?

Non-Celiac Gluten Sensitivity: diagnosis

Exclude celiac disease & wheat allergy
Negative TTG, EMA, DGP, & IgE antibodies
No villous atrophy
May have positive anti-gliadin antibodies, but not

diagnostic
May have subtle changes to small intestine further

research needed

Irritability, attention deficit, anxiety, depression

Exclude diagnosis of other inflammatory conditions

Diarrhea or constipation

Positive response to gluten-free diet

Heart burn, dyspepsia

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Associated with GRD

Objective:

Fibromyalgia 6.7%

Recommend appropriate medical nutrition therapy for

Irritable bowel syndrome

gluten-related disorders

Autism
Inflammatory bowel diseases 4-8%
Autoimmune thyroid (Hashimotos, Graves) 2-7%
Scleroderma 4%
Sjogrens - 4%
Type 1 diabetes 8%
Eating disorders 11-20%
Encourage follow-up with specialists to obtain correct

diagnosis and any necessary continued care

Treatment: gluten free diet

STRICT lifelong adherence ( CD, DH, GA NCGS, WA unknown)
Remove from diet:
Wheat, rye, triticale
Barley: malt, malt flavor, malt vinegar
Oats not labeled gluten-free
Brewers yeast
Prevent cross-contact with gluten
At home: separate cutting boards, toasters, colanders, condiments
Restaurants: speak with manager/chef about procedures they can
take to prevent cross-contact
Air-born flour esp pizza parlors, bakeries, and at home
Fried foods

Ingredients processed to remove gluten (i.e. wheat

starch) must meet <20 ppm prior to adding to final product

and contain disclaimer:
*The wheat has been processed to allow this food to meet the Food

and Drug Administration requirements for gluten-free foods

Gluten-Free Labeling
FDA-regulated foods, including imports, effective

8/5/14
Must contain <20 ppm gluten
Safe for vast majority of celiacs, but not all
Does not have to be tested, but recommended
Includes:
gluten-free beer (bc not made with hops)
supplements
Excludes USDA products, medications, cosmetics
90% of USDA products comply with FDA regulations
Only 11 of approx 5,000 medications contain gluten

Gluten-Free Labeling cont.

Does not apply to food service, but encouraged

by FDA
Food service regulated by local governments

May contain wheat/gluten or Processed in a

facility that also processes wheat/gluten

Voluntary label
May occur concurrently with gluten-free label, and

must still meet <20 ppm standard

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Can we trust the label?

Survey of GF-labeled vs. unlabeled foods in US, 2015

FDA market survey

98.9% labeled GF foods met <20 ppm
19% naturally GF foods (not labeled) contained >20 ppm
Most at risk for gluten content cereals, oat products, grain

products with advisory statements

Survey of certified GF foods vs. labeled GF foods in US,

2011-2014 Thompson & Simpson

95% tested below 20 ppm
87% tested below 5 ppm
No significant difference between labeled and certified foods

neither is fail-proof

Tips for navigating the GFD

Dietary considerations on GFD

Dont worry about:

Maltodextrin
Natural flavor
Blue cheese
Wine/wine barrels, tea
bags
Envelopes/stamps
Topical cosmetics
Medications

Check nutrient levels & supplement as indicated:

Vitamin D
Full iron panel
B12, folate
Zinc

Be weary of:
Wheat grass, barley grass
Grain-based products not
labeled GF
USDA foods &
medications that contain
food starch or modified
food starch (undeclared
source)
Gluten-removed beer
All food service

Weight gain
Common in first year after initiating GFD, especially in CD
Calorie needs may be lower now that absorption is increased
GF foods may be more calorically-dense
Adequate fiber intake: only 50% get DRI fiber
Adequate B vitamin, iron, calcium, magnesium intake

Unknown: personal care products used in the mouth

Nutrient Comparison:

Cereal

Nutrient Comparison:
Whole Grain Bread

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Objective:

Continued Symptoms on GFD

Be familiar with co-occurring disorders which may impact

Effecting approx. 20-50% of those dx with CD + NCGS

patients with gluten-related disorders

Continued gluten exposure 30-50%
Lactose & fructose intolerance 50% + ?
Secondary lactase deficiency may resolve after months-years on
GFD d/t regrowth of villi and production of enzyme
Breath testing may be diagnostic, but standards vary greatly
Comprehensive digestive enzymes may aid symptoms in beginning

while villi are healing

Continued Symptoms on GFD

Case Study

Irritable bowel syndrome 30%

17 yo female: diagnosed with celiac disease by ND

Small intestinal bacterial overgrowth 10 - 40%?

May manifest as continued malabsorption and GI/mood symptoms
similar to in CD
No evidence-based dietary treatment for SIBO
Low FODMAP diet helpful for symptom relief in most cases

Continuing symptoms despite GFD x 7 months

Diagnostic tests performed:

Microscopic colitis 4%
Pancreatic insufficiency 10-20%
Supplemental enzymes
Inflammatory bowel diseases 3.6 - 8.5%

TTG negative
Total IgA normal
AGA IgG positive for wheat, negative for barley & rye
IgE positive for corn

Symptoms:
Swollen lymph nodes
Fatigue
Iron-deficiency anemia
Frequent colds
Alternating diarrhea/constipation

Resources for the RD

References

AND Toolkit

Ludvigsson JF, Leffler DA, Bai J, Biagi F, Fasano A, Green PH,

GlutenFreeWatchdog.org
International Celiac Disease Symposium
Celiac.org monthly webinars, annual conference in

Pasadena
Pillbox - http://pillbox.nlm.nih.gov/
The Gluten-Free Diet: A comprehensive Resource Guide

by Shelley Case

Hadjivassiliou M, Kaukinen K, Kelly C, Leonard J, Lundin KE, Murray

JA, Sanders DS, Walker MM, Zingone F, Ciacci C. The Oslo
definitions for coeliac disease and related terms. Gut. 2013 January;
62(1): 43-52. doi: 10.1136
Thompson T, Dennis M, Higgins LA, Lee AR, Sharrett MK. Gluten-free
diet survey: are Americans with coeliac disease consuming
recommended amounts of fibre, iron, calcium and grain foods?.
Journal of Human Nutrition and Dietetics. 2005 June; 18(3):163-9.
Leeds JS, Hopper AD, Hurlstone DP, Edwards SJ, McAlindon ME,
Lobo AJ, Donnelly MT, Morley S, Sanders DS. Is exocrine pancreatic
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Alimentary Pharmacological Therapy. 2007;25:265-71.
Thompson T, Simpson S. A comparison of gluten levels in labeled
gluten-free and certified gluten-free foods sold in the United States.
European Journal of Clinical Nutrition. 2014 October; 1-4.

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References

References

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Medical Professionals Guide. University of Chicago Celiac Disease
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Dermatitis herpetiformis. Celiac Disease Foundation.
http://celiac.org/celiac-disease/dermatitis-herpetiformis/
Gluten ataxia. About.Health.com.
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References

References

Hadjivassiliou M, Davies-Jones GAB, Sanders DS, Grunewald

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