Celiac Disease Pentax Research Grant (ergonomics) & Non-Celiac - - PowerPoint PPT Presentation

6/20/2018

Celiac Disease & Non-Celiac Gluten Sensitivity

Amandeep Shergill, M.D., M.S.

Associate Clinical Professor of Medicine University of California, San Francisco Director of Endoscopy, San Francisco VA Medical Center

Disclosures

• Pentax Research Grant (ergonomics)

Celiac Disease & Non-Celiac Gluten Sensitivity

• Celiac Disease
• Pathophysiology
• Prevalence
• Presentation
• Diagnosis
• Mortality & Morbidity
• Treatment
• Non-celiac Gluten Sensitivity

Case Scenario

• 28 yo female
• 6 year h/o “IBS”: abd gas, bloating, diarrhea alternating with

constipation

• Tried on multiple medications without relief
• Friend told her she might have Celiac Disease and should get herself

tested

6/20/2018

Case Scenario

• “Doc – what is celiac disease? “

Celiac Disease

• “What is celiac disease?”
• Chronic small intestinal immune-

mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals

Ludvigsson, BMJ 2013.

Pathogenesis of Celiac Disease: Gluten

• Wheat
• Rye
• Barley

Pathogenesis of Celiac Disease: Gluten

• Wheat
• Rye
• Barley

Shan Science 2002

6/20/2018

bio.davidson.edu; http://escapinganergy.blogspot.com/2011/05/hold-carrots-vitamin-may- exacerbate.html

Pathogenesis of Celiac Disease: Gluten

Figure from glutenpost.com

Genetic Factors: HLA-DQ2/HLA-DQ8

Kagnoff, Gastro 2005;128:S10-18.; https://commons.wikimedia.org/wiki/File:HLA-DQ2.5_gliadin.PNG

• 25-30% Caucasian population DQ2/8 positive
• 4% of DQ2/8 positive individuals exposed to gluten develop CD

Pathogenesis of Celiac Disease

Host

• HLA:DQ2/DQ8
• Non HLA genes

Triggers

• Wheat
• Barley
• Rye

Cofactors

• Intestinal Infections
• Infant feeding

practices

• Socioeconomic

factors

Di Sabatino, Lancet 2009

6/20/2018 Incidence of Celiac Disease: active duty US military

Riddle AJG 2012 “Incidence of CD diagnosis in a healthy US adult population is increasing…and appears higher than other population-based estimates”

Increasing prevalence over time: serological studies, 2-4x higher prevalence

• Two large Finnish population-based studies
• 20y apart
• tTG and EMA antibodies
• doubling in CD prevalence from 1978– 1980 to 2000–

2001

• American study compared sera collected between 1948 and

1954 with two matched cohorts collected between 1995 - 2003 and between 2006 -2008 respectively

• Prevalence of CD was 4x higher in the recent cohorts
• Retrospective analysis of matched serum samples taken

from US community volunteers in 1974 and 1989 showed a doubling in prevalence

Khang et al; Aliment Pharmacol Ther 2013; 38: 226-245; Rubio-Tapia Gastro 2009

Incidence of Celiac Disease: Pediatrics

Almallouhi JPGN 2017 Lebwhol BMJ 2015

6/20/2018 Environmental Risk Factors:

• Infection:
• Rotavirus infection an independent risk factor for celiac disease in

pediatric onset CD

• Changes the permeability of and the cytokine balance in the

intestinal mucosa

• Suggested risk of CD after Campylobacter infection, but not other

foodborne infections.

• Infant feeding practices
• Breastfeeding
• Gluten introduction

Tack et al, NatRevGastroHep 2010; Riddle DDS 2013; Riddle AJG 2012; Nadal J Med Micorbiol 2007

Environmental Risk Factors

• Swedish epidemic:
• 3x higher CD

prevalence with change in national recommendations

Ivarsson, Acta Ped 2000; Silano WJG 2010.

Environmental Risk Factors: Infant feeding

• “Failure of oral

tolerance to gluten”

• Potential mechanisms:
• Immunomodulatory

activity breast milk:

• bifidobacteria
• infection
• Amount of gluten

introduced

Ivarsson, Best Prac Reas Clin Gastro 2005; Nadal, J Med Microbio 2007; Silano WJG 2010.

PreventCD TRIAL: early introduction of gluten

• Multicenter, randomized, double-blind, placebo-controlled dietary

intervention study

• ?window of opportunity of first gluten exposure – primary prevention
• Exposing genetically predisposed infants to small quantities of gluten at 16 to

24 weeks of age, preferably while they were still being breast-fed

• 944 children: positive for HLA-DQ2 or HLADQ8, at least one first-

degree relative with celiac disease.

• 16-24 weeks of age (8 weeks):
• 475 participants received 100 mg of immunologically active gluten daily
• 469 received placebo.
• After the intervention, parents were advised to introduce gluten gradually,

using regular products and standardized recommendations

• Primary outcome: frequency of biopsy-confirmed celiac disease at 3

years of age

Vriezinga SL et al. N Engl J Med 2014;371:1304-1315.

6/20/2018

VriezingaSL et al. N EnglJ Med 2014;371:1304-1315.

PreventCD TRIAL: early introduction of gluten (16 weeks)

* Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention

Risk of Celiac Disease and Age at Gluten Introduction CELIPREV TRIAL: gluten at 6 vs 12 m

• Multicenter, prospective intervention trial comparing early and delayed

introduction of gluten to the diet of infants with a familial risk of celiac disease, and followed these children from birth to at least 5 years of age.

• 832 newborns: first-degree relative with celiac disease
• Randomized to the introduction of dietary gluten: at 6 months (group A) or

12 months (group B).

• At 12 months of age, all children began to receive a normal diet containing gluten.
• HLA genotype: was determined at 15 months of age
• Serologic screening for celiac disease:
• evaluated at 15, 24, and 36 months
• and at 5, 8, and 10 years
• Patients with positive serologic findings underwent intestinal biopsies.
• Primary outcome was the prevalence of celiac disease autoimmunity and of
• vert celiac disease among the children at 5 years of age.

Lionetti NEJM 2014

CELIPREV TRIALS: gluten at 6 vs 12 m

• 2 years of age: Group A vs Group B
• Celiac disease autoimmunity

significantly greater (16% vs. 7%, P = 0.002)

• Overt celiac disease significant greater

(12% vs. 5%, P = 0.01)

• 5 years of age: between-group

differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P = 0.59) or overt disease (16% and 16%, P = 0.78 by the log-rank test)

• 10 years: risk of celiac correlated

with high-risk HLA

Lionetti NEJM 2014

Postponing the introduction of gluten

• Delayed the development of

celiac disease

• which might reduce the

negative effect of the disease

• n vulnerable organs such as

the brain.

• Reduced the prevalence

(nonsignificantly) of celiac disease autoimmunity at any age among children carrying the high-risk HLA genotype

• Did not detect an effect of

breastfeeding on the development of celiac disease

Lionetti NEJM 2014

6/20/2018 Breastfeeding during Gluten Introduction

Chmielewska Ann Nutr Metab 2015

GLUTEN INTRODUCTION AND THE RISK OF COELIAC DISEASE: A POSITION PAPER BY THE EUROPEAN SOCIETY FOR PAEDIATRIC GASTROENTEROLOGY, HEPATOLOGY & NUTRITION

• Although breastfeeding should be promoted for its other well-established

health benefits, neither any breastfeeding nor breastfeeding during gluten introduction has been shown to reduce the risk of CD.

• Gluten may be introduced into the infant’s diet anytime between 4-12

completed months of age.

• In children at high risk for CD, earlier introduction of gluten (4 vs. 6 mo or 6
• vs. 12 mo) is associated with earlier development of CD autoimmunity

(defined as positive serology) and CD, but the cumulative incidence of each in later childhood is similar.

• Based on observational data pointing to the association between the

amount of gluten intake and risk of CD, consumption of large quantities of gluten should be avoided during the first weeks after gluten introduction and during infancy. However, the optimal amounts of gluten to be introduced at weaning have not been established. Szajewska JPGN 2016

Inflammation process and possible routes of probiotic action in the maintenance of CD. In CD patients, increased epithelial tight junction permeability (“leaky gut”) favors the entrance of non- well-digested gluten peptides from the lumen to the lamina propria.

Luís Fernando de Sousa Moraes et al. Clin. Microbiol. Rev. 2014;27:482-489

Environmental Risk Factors: Microbiome

• Children who were born via elective Caesarian section are at

increased risk of developing celiac disease, while those born via emergent Caesarian section (and may have had contact with the birth canal) are not

• Inverse relationship between Helicobacter pylori colonization and

celiac disease

• Population-based studies from Sweden have shown that prescription
• f antibiotics and proton pump inhibitors are each associated with

an increased risk of the subsequent development of celiac disease.

Lebwohl CGH 2014; Marild Gastroenterology 2012; Lebwohl Am J Epidemiol 2013; Marild BMC Gastroenterol 2013; Dig Liver Dis. 2013.

6/20/2018 Environmental Risk Factors: Socioeconomic Factors

• Russian Karelia vs. Finland
• Remote territory of Russia –

“They live like Finns 50 years ago.”

• 2004: Karelia GNP=$3410
• Vs. Finland GNP=$32,790
• TTG ab: 0.6% versus 1.4%

(P=.005)

• Biopsy proven CD:
• Prevalence of 1:496 Karelian

children compared to 1:107 Finnish children

Tack et al, NatRevGastroHep 2010; Kondrashova Ann Med 2008; Velasquez-Manoff, NYT 2013 .

Environmental Risk Factors: Microbiome

• Worse conditions might protect

against CD

• Variations in gut flora
• Infections – hygiene hypothesis
• Analysis of house dust and potable

water:

• Russian Karelians encountered a greater

variety and quantity of microbes, including many that were absent in Finland. Velasquez-Manoff, NYT 2013

Pathogenesis of Celiac Disease

Host

• HLA:DQ2/DQ8
• Non HLA genes

Triggers

• Wheat
• Barley
• Rye

Cofactors

• Intestinal Infections
• Infant feeding

practices

• Socioeconomic

factors

• Microbiome

Di Sabatino, Lancet 2009

Case Scenario

• “How common is it?”

6/20/2018

How common is celiac disease?

• A. 1:10
• B. 1:50
• C. 1:100
• D. 1:500
• E. 1:1000

1 : 1 1 : 5 1 : 1 1 : 5 1 : 1

0% 16% 21% 16% 47%

Celiac Disease Prevalence

• “How common is it?”
• US: 1:100 (range 1:80 to 1:140)

Green AJG 2007

What continent has the highest known prevalence of celiac disease?

• A. North America
• B. South America
• C. Europe
• D. Australia
• E. Asia
• F. Africa

N

• r

t h A m e r i c a S

• u

t h A m e r i c a E u r

• p

e A u s t r a l i a A s i a A f r i c a

44% 0% 0% 3% 0% 53%

Celiac Disease Prevalence

Country Adults Children Europe 0.18-2.6% 0.2- 1.3% Germany 0.3 0.2 Great Britain 1.2 1.0 Finland 0.5-2.6 1.0 Italy 0.7 0.54-.085 Russia 0.2 NA North and South America 0.15-2.6 0.9% Mexico 2.6 NA USA 0.4-0.95 0.9 Asia 0.6-1.6 0.02-1.0 India NA 1.0 Syria 1.6 NA Africa 0.28 0.64-5.6 Algeria NA 5.6 Tunisia 0.28 0.64 Tack, Nature Review Gastro Hep 2012; Mustalahti, Annals Med 2010

6/20/2018

Celiac Disease Prevalence

Country Adults Children Europe 0.18-2.6% 0.2- 1.3% Germany 0.3 0.2 Great Britain 1.2 1.0 Finland 0.5-2.6 1.0 Italy 0.7 0.54-.085 Russia 0.2 NA North and South America 0.15-2.6 0.9% Mexico 2.6 NA USA 0.4-0.95 0.9 Asia 0.6-1.6 0.02-1.0 India NA 1.0 Syria 1.6 NA Africa 0.28 0.64-5.6 Algeria NA 5.6 Tunisia 0.28 0.64 Tack, Nature Review Gastro Hep 2012; Mustalahti, Annals Med 2010

Worldwide Seroprevalence of Celiac Disease

Singh CGH 2017

Worldwide Biopsy Proven Prevalence CD

Singh CGH 2017

Celiac Disease Prevalence: “New Epidemiology”: Saharawi children

• Highest known prevalence of

CD

• Genetic factors: high

frequency of HLA DQ2

• Arabic and Berber

ancestry

• Environmental factors:
• live as refugees in Algeria
• rates and duration of

breast feeding reduced

• large amount of wheat

consumption in early life – humanitarian aids from western countries

Cataldo, WJG 2007

http://diasporasaharaui-en.blogspot.in/2013/12/unsuitable- international-food-aid-case.html

6/20/2018 Celiac Disease Prevalence: “New Epidemiology”: Punjab

• Genetic predisposition – Aryan descent with HLA-

predisposing genes

• Environmental factors
• “summer diarrhea”
• wheat typical staple food (chapattis, roti)
• winter – maize (makhi roti)
• 2016 study: >450,000 duodenal biopsy samples

taken from people throughout the USA

• prevalence of villous atrophy calculated for

ethnicities using a previously published name based algorithm

• highest prevalence of villous atrophy:

descendants of Punjab area of northern India (3.08% vs 1.80% for other Americans)

Cataldo, WJG 2007; Krigel Clin Gastroenterol Hepatol 2016.

Celiac Disease Prevalence: “New Epidemiology”

• Worldwide public health

problem

• Involves all ethnic groups in all

the areas of the world where there is great consumption of wheat

• “westernization” diet
• humanitarian interventions

Cataldo, WJG 2007

Celiac Iceberg

• The ratio of diagnosed

to undiagnosed cases

• f CD is thought to be

highly variable

• 1 : 2 in Finland
• 1 : 20 in Argentina, US
• Most cases undetected
• US: National Health and

Nutrition Examination Survey (considered representative of the US population): , showed that more than

• >80% of people with

coeliac disease were undiagnosed in 2009

• decreased to <50% in

2013–14

WGO Celiac Guidelines 2012; Choung Mayo Clin Proc 2016 Grossman Pract Neurol 2008; 8: 77–89

6/20/2018

Screening for Celiac Disease US Preventive Services Task Force Recommendation

• The USPSTF concludes that the current evidence is insufficient to

assess the balance of benefits and harms of screening for celiac disease in asymptomatic persons. (I statement)

USPSTF JAMA 2017

Celiac Disease: a systemic disease

• General
• Growth delay
• GI
• Diarrhea, malabsorption
• Constipation
• hepatitis
• Skin:
• Dermatitis herpetiformis

Rewers, Gastro 2005;128:S47-51.

Dermatitis Herpetiformis

• Cutaneous manifestation of gluten sensitivity
• extensor surfaces of the elbows, knees, buttocks, and back
• pruritic

Emedicine.medscape.com

Celiac Disease: a systemic disease

• General
• Growth delay
• GI
• Diarrhea, malabsorption
• Constipation
• hepatitis
• Skin:
• Dermatitis herpetiformis
• Metabolic bone disease
• Neurologic
• Depression, epilepsy, migraine
• Gluten ataxia
• Endocrine
• Type I DM, thyroid disease
• Cardiovascular
• Infertility

Rewers, Gastro 2005;128:S47-51.

6/20/2018 High Risk Populations

• Relatives: 10%
• Fe def anemia
• Asymptomatic: 5% serology, 8.7% biopsy
• Symptomatic: 10.3-15%
• Should be considered in any adult with unexplained IDA, including

menstruating women

• Liver Disease:
• 1.5-9% LFT abnormalities of unknown cause
• Osteopenia/Osteoporosis
• 1% and 3.4%.
• Should be considered in any patient with premature-onset
• steoporosis
• Infertility
• The pooled relative risk of celiac disease in infertile women

compared with controls was 3.7 (95% CI, 1.3–10.4).

AGA Technical Review, Gastro 2006

Detection of CD in Primary Care:

A multicenter case-finding study in North America

• Multicenter, prospective study 2002-2004
• Questionnaire to individuals over 18yo soliciting:
• Symptoms
• Diarrhea
• Abdominal pain, constipation
• Chronic fatigue
• Infertility
• Epilepsy or ataxia
• Abnormal lab values
• Anemia
• LFTs
• Associated diseases
• IBS
• Autoimmune
• Down’s syndrome
• Turner’s syndrome
• Family h/o celiac disease

Catassi et al, AJG 2007

Detection of CD in Primary Care:

A multicenter case-finding study in North America

• 38% (976/2568) responded affirmatively 1+ items
• CD diagnosed in 2.25% (22/2568)
• Most frequent reason: bloating (12), thyroid disease (11),

IBS (7), unexplained chronic diarrhea (6), chronic fatigue (5), constipation (4)

• Following implementation of active screening
• 32-43 fold increase in diagnosis of CD

Catassi, AJG 2007

Indications for testing for celiac disease: case-control study of adults w/o prior diagnosis of celiac disease.

Hujoel APT 2018

6/20/2018 Celiac Disease and IBS: Systematic Review and Meta-analysis

Irvine et al, AJG 2016

Diagnosis in Elderly

• Approximately a quarter of all diagnoses are now

made at the age of 60 years or more

• A fifth are made at 65 years or over
• 4% are diagnosed at 80 years or above.
• Around 60% remain undetected
• symptoms subtle: tiredness, indigestion, reduced

appetite.

• Compliance with gluten free diet, resolution of

symptoms and improvement in laboratory indices can be achieved in over 90% of patient

Collin APT 2018

Case Scenario

• “How do we diagnose it?”

What is the best way to screen for celiac disease?

• A. Gluten challenge
• B. Endoscopy with biopsy
• C. Serum IgA anti-gliadin antibody
• D. Serum IgA anti-endomysial antibody
• E. Serum IgA tissue transglutaminase

G l u t e n c h a l l e n g e E n d

• s

c

• p

y w i t h b i

• p

s y S e r u m I g A a n t i

• g

l i a d i n a . . . S e r u m I g A a n t i

• e

n d

• m

y s i . . S e r u m I g A t i s s u e t r a n s g l . . .

3% 9% 66% 9% 13%

6/20/2018 Serology

• IgA tTG: preferred single test
• IgA EMA: more time consuming, operator dependent
• IgA deficiency: 2-3% patients with CD

AGA Technical Review, Gastro 2006; ACG Celiac Guidelines 2013.

Serology

Rashid Can Fam Physician 2016;62:38-43

Endoscopy with Biopsy for Diagnosis:

• Endoscopic sings:
• Decrease in duodenal

folds

• Scalloping of folds
• Mucosal fissures
• Nodularity
• 4-6 biopsies
• Including duodenal bulb

Green et al, Gastro 2005;128:S74-8. Kragnoff, Gastro 2005;128:S10-8.

Samir at en.wikipedia

Pathological Diagnosis

• Villous atrophy
• Crypt hyperplasia
• Increased intraepithelial

lymphocytes: >30-40 per 100 surface enterocytes

Dewar et al, Gastro 2005;128:S19-24. Kagnoff, Gastro 2005;128:S10-8.

https://upload.wikimedia.org/wikipedia/commons/b/be/Normal_Small _Intestine_Mucosa_%285916217283%29.jpghttps://commons.wikimedi a.org/wiki/File:Celiac_disease_-_high_mag.jpg

6/20/2018

Case Scenario

• “Will I get cancer? Am I going to

die from it?”

Mortality in Undiagnosed Celiac Disease

• Study results variable
• Ab screen on stored serum samples, matched to mortality data
• Four studies: no increased mortality (UK, Finland, US elderly)
• Two studies: SMR 2.53 -4 (Germany, USA)

Biagi, Nat Rev Gastro Hep 2010

Mortality

• Increased risk for all-cause mortality in celiac patients:

OR 1.24; 95% CI 1.19–1.30

Tio APT 2012

Mortality

• Increased risk for NHL in celiac patients:

OR 2.61; 95% CI 2.04–3.33).

Tio APT 2012

6/20/2018 Mortality

• Increased risk for enteropathy associated T cell lymphoma

in celiac patients: OR 15.84; 95% CI 7.85–31.94

Tio APT 2012

Mortality

• No increased risk for any malignancy in celiac patient:

OR 1.07; 95% CI 0.89–1.29)

Tio APT 2012

Mortality in Celiac Disease

• Dominant cause of death:
• cardiovascular death: 20% increased risk
• increased risk of ischemic heart disease, stroke, atrial

fibrillation and potentially also autoimmune heart disease

• malignancy
• GFD appears protective
• Adherence: no excess mortality
• Unlikely to comply: SMR 2x higher
• Definitely noncompliant: SMR 6x higher
• SMR correlated to severity of presentation
• Risk of mortality decreased over time

Biagi, Nat Rev Gastro Hep 2010; Ludvigssson Gastrointest Endoscopy Clin N AM 2012.

Mortality in Undiagnosed Celiac Disease

Rubio-Tapia et al, Gastro 2009

• 9133 healthy young adults at

Warren Airforce Base

• TTG, anti-endomysial ab

testing

• During 45 years of follow-up,

undiagnosed CD was associated with a nearly 4- fold increased risk of death.

6/20/2018 Morbidity in Undiagnosed Celiac Disease

• Undiagnosed maternal celiac disease
•  risk of infertility, spontaneous abortions
•  preterm birth and ceasarean section rates
• negative effect on intrauterine growth/ birth weight
• Associated with increased fracture risk
• Associated with increased risk of lymphoma and small bowel

cancer

• although overall rates are low

NICE Celiac Guidelines 2009; ACG Celiac Guidelines 2013.

Case Scenario

• “Oh, I already feel so much

better after starting on the diet…”

Common Pitfalls in Diagnosis of CD

• Gluten reduced diet may reduce sensitivity of

serological screening and the severity of lesion on pathology

• Negative test in the setting of GFD not conclusive
• 4-6 week challenge with “sufficient” gluten
• ACG: 3g gluten challenge for 2 and then 6 weeks

AGA Technical Review, Gastro 2006; NICE Celiac Guidelines 2009; ACG Celiac Guideline 2013

Case Scenario

• “No way am I going back on a

gluten diet…”

6/20/2018 HLA-DQ2 and DQ8

• Sensitivity 100%
• Absence of these

alleles provides a NPV close to 100%

• Poor specificity
• Approximately 25%–

40% of the general population in the United States carry the HLA class II heterodimer HLA-DQ2

• r HLA-DQ8
• Necessary but not

sufficient for diagnosis of CD

AGA Technical Review, Gastro 2006

https://commons.wikimedia.org/wiki/File:HLA-DQ2.5_gliadin.PNG

ACG Guideline Celiac Disease 2013

Gluten Free Diet (GFD)

GFD

• Only effective treatment for CD
• Avoidance of wheat, rye, barley
• Found in bread, biscuits, cakes, pastries,

breakfast cereals, pasta, beer and most soups, sauces (including soy sauce), and puddings

• Supplements, medications
• Registered Dietician

Green, NEJM 2007; ACG Celiac Guidelines 2013.

6/20/2018

Monitoring Celiac Disease

• Patients with celiac disease should be evaluated at

regular intervals by a health care team including a physician and a dietician.

• Repeat serologic testing after 3-6 months on a GFD
• the serologic test results tend to become negative

as the histologic findings improve

• 80% at one year; 99% at 5 years
• sensitivity for minor dietary indiscretion can be

LOW

• Followed at least annually

AGA Technical Review, Gastro 2006; ACG Celiac Guidelines 2013.

ACG Guideline Celiac Disease

Kelly Gastro 2015

Management of Celiac Disease

• Cardiovascular prevention:
• Cessation of smoking
• Treatment of hypertension
• Treatment of hyperlipidemia
• Encouraging physical activity
• Avoiding obesity: Dickey AJG 2006 - 39% overweight @ dx
• Metabolic bone disease: DEXA
• Thyroid disease: TSH
• Hyposlenism: prophylactic pneumococcal vaccination

Ludvigsson Gastointest Endoscopy Clin N AM 2012; Lewis ExpRev Gastro Hep 2010.

6/20/2018 Celiac Disease

• Pathophysiology – gaps in knowledge
• Prevalent disease with associated morbidity and mortality
• Diverse populations
• Diverse presentations
• Screening: sensitive and specific serology
• Treatment is effective, low risk/ high benefit

Case 2

• 64yo male with extensive work up for abdominal pain, gas/bloating,

negative for celiac disease (negative serology, negative biopsy), but insistent that he cannot tolerate gluten.

Gluten Goodbye: One-Third Of Americans Say They're Trying To Shun It

• "Right now 29 percent of the adult population says, 'I'd like to cut back
• r avoid gluten completely”
• NPR, March 9 2013 by Nancy Shute

Non-Celiac Gluten Sensitivity

• IBS- like symptoms occurring after the ingestion of gluten
• Abdominal pain, bloating, diarrhea, flatulence
• Negative celiac serology, normal histology
• Ruled out wheat allergy (skin prick, serum IgE)
• Symptoms disappear after gluten is withdrawn from the diet
• Symptoms re-present after double blind placebo controlled gluten re-

challenge

Di Sabatino, J Clin Gastro 2013; Sapone BMC 2012

6/20/2018

Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind Placebo-Controlled Challenge: Exploring a New Clinical Entity

Carroccio AJG 2012 1/3

Double blind placebo controlled trial

Corroccio AJG 2012.

Double blind placebo controlled crossover challenge: 59 subjects

Skodje Gastro 2018

Wheat: Gluten Fructans Soluble proteins

Double blind placebo controlled crossover challenge: 59 subjects

Skodje Gastro 2018

6/20/2018 FODMAPs

Gastroenterological Society of Australia, Digestive Health Foundation 2013

FODMAPs

Staudacher Gut 2017

True or False: A gluten free diet is naturally healthy, and will not result in any nutritional deficiencies.

• A. True
• B. False

T r u e F a l s e

69% 31%

Gluten Free Diet

• Difficult:
• Food availability
• Food contamination
• Expensive
• Canadian study: gluten-free products 242% more

expensive

• Potential nutritional deficiencies

Stevens Can J Diet Pract Res 2008; Cureton Practical Gastro 2007

6/20/2018 Gluten Free Diet: Deficiencies

• fiber
• iron
• folate
• B complex vitamins
• calcium
• magnesium
• vitamin A
• zinc
• riboflavin

Shepherd, J H Nutrition & Dietetics 2012

Gluten Free Diet: Deficiencies

• fiber
• iron
• folate
• B complex vitamins
• calcium
• magnesium
• vitamin A
• zinc
• riboflavin

Shepherd, J H Nutrition & Dietetics 2012; ACG Celiac Guidelines 2013.

*Oats improves the nutrient content of GFD GFD: Weight Gain

• At diagnosis: 90% of the study population were at normal weight or

with a body mass index (BMI) > 20

• 81% of the population gained weight when on the gluten-free diet.
• Of the study population that was obese, 82% gained more weight

Dickey AJG 2006

Heavy Metal Accumulation: National Health and Nutrition Examination Survey 2009 through 2012 - GFD

Blood

• Mercury levels (1.37 mcg/L) compared

with persons not on a GFD (0.93 mcg/L) (P =.008)

• Lead (1.42 vs 1.13 mcg/L; P= .007)
• Cadmium (0.42 vs 0.34 mcg/L; P=.03)

Urine

• Arsenic (15.15 mcg/L) than

urine samples from subjects not

• n a GFD (8.38 mcg/L) P= .002

Raehsler CGH 2018

Avoidance of gluten -> heavy reliance on rice as a staple grain

6/20/2018 Non Celiac Gluten Sensitivity

• Likely related to fructans in diet
• non celiac wheat sensitivity
• GFD is not without harm: weight gain, vitamin/ mineral

deficiencies, heavy metal accumulation

• Diet -> Microbiome
• Dietician referral for guidance

Photo courtesy of Dr. Quinny Cheng