1. What’s New in Sprue (near you)
Ciarán P. Kelly, MD
Professor of Medicine
Harvard Medical School
&
Director, Celiac Center
BIDMC, Boston

2. What’s New in Sprue International Celiac News
How common is celiac disease? A moving target
Why are so many people eating Gluten Free (and does it help me)?
News from BIDMC Celiac Center
Making gluten challenge less challenging
The burden of treating celiac disease - a difficult pill to swallow
Progress toward new treatments for celiac disease
Getting fat gluten free & why it’s good to have celiac disease
CeliacNow.org – Celiac disease & the GFD in digestible bytes
More Celiacologists come to Boston

3. The World View of Celiac Disease 1989
Ireland
1/300
Europe 1/1000
North America
CD Rare
1/5000
South America
Africa
Asia
CD Rare

4. TTG serology enables increased celiac disease diagnosis
PCPs “discover”
TTG blood test
(Tissue TransGlutaminase)
What happened here?
Garud et al. Aliment Pharmacol Ther 2009;29(8):

5. Where is celiac disease most common?
1980’s - Galway Ireland
The “capital of celiac disease”
Estimated 1 in 303 in 1980’s
1990’s – United States
Estimated 0.02% (1/5000)
2000’s – US & Most of the world
Estimated ~1%
Finland
2000 1% (half diagnosed)
2010 2% (quarter diagnosed)

6. Common & Not Limited to Europeans
Today’s World View of Celiac Disease
Finland:
~2.5%
North America
& Europe
0.6 to 2.5%
Northern India
?3%
SouthEast
Asia
CD Rare
Subsaharan
Africa
CD Rare

7. An expanded perspective
Celiac disease
An expanded perspective
Who?
Common in many ethnic backgrounds
When?
Any age after gluten ingestion
Average age at diagnosis ~45 yrs
How?
Highly diverse presentations.
Average 11 years of symptoms prior to diagnosis
Celiac Disease Foundation
Green AJG 2001, Cranney DDS 2007

8. Celiac disease now more common in the US?
Or just more commonly diagnosed?
Then:
9,133 healthy young adults at Warren Air Force Base
1950: Blood collected (1948 to 1954)
0.2% with CD (positive TTG)
Now:
12,768 gender-matched subjects from 2 recent US cohorts
Circa 2000:
Similar years of birth (n = 5558)
Similar age at sampling (n = 7210)
0.9% with CD [x 4.5; P < .001].
Mortality hazard ratio = 3.9
(95% CI, ; P < .001)
Conclusions:
Celiac disease 4 times more common now than 50 years ago
4 fold increased risk of death with undiagnosed CD over 50 year time period
Rubio-Tapia A et al. Gastroenterol 2009;137: Lohi S et al. Aliment Pharmacol Ther 2007;26:

9. Rising incidence of auto-immune & allergic conditions
CD in
Finland
United States
Type I
Diabetes
Bach JF, NEJM 2002, Lohi et al. APT 2007, Rubio-Tapia Gastro 2009

10. Why is celiac disease more common?
“An idle immune system is the devil’s playground”
Why are many “auto-immune” and allergic conditions increasingly common?
Hygiene theory
Our immune system developed to constantly fight germs and parasites
Modern hygiene leads it to react against harmless environmental antigens and auto-antigens

11. What’s New in Sprue International Celiac News
How common is celiac disease? A moving target
Why are so many people eating Gluten Free (and does it help me)?

12. Intestinal damage in Celiac disease & healing on the Gluten Free Diet
Flat Villi
Healthy Villi

13. Neither can tolerate it
Small bowel biopsies
Which person can’t eat gluten?
Normal Villous atrophy
Neither can tolerate it
Slide Atlas of Gastronterology, Misiewicz et al, 1984

14. Non-Celiac Gluten Sensitivity
Theories:
Imaginary?
Psycho-somatic?
Irritable bowel syndrome variant?
A result of gluten’s:
Indigestibility
Ability to activate “innate” immunity
versus activation of adaptive immunity in celiac disease
INSERT your pet theory HERE

15. Non-celiac gluten sensitivity
Similar & significant differences for: Abdominal pain, bloating, tiredness & satisfaction with stool consistency
NCGS is a real phenomenon
Celiac disease cannot be diagnosed by a GFD trial

16. Gluten & wheat associated disorders
Celiac disease
Non-celiac Gluten Sensitivity
Wheat allergy
~1%
of population
> 1%
< 1%
Positive IgA tTG antibody test
Abnormal biopsy
Symptoms on gluten exposure [after allergy and celiac disease excluded]
History (food diary)
Skin / RAST

17. Celiac disease versus NCGS (Non-celiac gluten sensitivity)
Gluten in diet causes:
Symptoms
Intestinal injury
High celiac antibodies
Malabsorbtion &
Nutritional deficiencies
Complications
Osteoporosis, malignancy
Genetic predisposition
Associated with other auto-immune disorders
Requires lifelong, strict GFD
Gluten in diet causes:
Symptoms
No known genetic predisposition
No known complications
Strictness & duration of GFD may vary

18. Non-celiac Gluten Sensitivity: The new kid taking over the block?
Pros for GFD:
More awareness. Easier access. Lower costs?
Cons for GFD:
Inconsistencies regarding strictness
New Yorker cartoon by GREGORY

19. What’s New in Sprue International Celiac News
How common is celiac disease? A moving target
Why are so many people eating Gluten Free (and does it help me)?
News from BIDMC Celiac Center
Making gluten challenge less challenging

20. aka Gluten free diet holiday:
Already on a Gluten Free Diet
but no formal diagnosis
Do I have celiac disease (or NCGS)?
Gluten challenge:
Typical regimen:
Full gluten diet for 8 weeks
Small intestinal biopsy & celiac antibody tests
Why bother?
Certainty re diagnosis
Celiac disease versus non-celiac gluten sensitivity
Certainty re need for lifelong, strict GFD
Certainty re family risk
Certainty re potential for celiac complications & associations
Can “cure” celiac disease!
aka Gluten free diet holiday: V

21. BIDMC Celiac center Gluten challenge study
Thank
You!
BIDMC Celiac center Gluten challenge study
Villous height falls on gluten exposure - but 3 g/day = 10 g/day

22. Gluten challenge: making it easier
Improvements:
Genetic test before challenge – if negative no challenge
Lower dose of gluten (3g versus 10-15g)
Option for 2 week dropout (>90% accuracy)
Late blood work to increase sensitivity further
Next steps?
Gluten challenge of biopsy
Gluten reaction “biomarkers” in blood 1. 3. 2. 4.
2013 American College of Gastroenterology Guidelines for Gluten Challenge in Celiac disease diagnosis (Am J Gastro in press)

23. What’s New in Sprue International Celiac News
How common is celiac disease? A moving target
Why are so many people eating Gluten Free (and does it help me)?
News from BIDMC Celiac Center
Making gluten challenge less challenging
The burden of treating celiac disease - a difficult pill to swallow

24. Is There a Role for Non-Dietary Celiac Disease Treatment?
Controversial in the past
Now widely accepted
Better medical & scientific data
A more diverse celiac population
From expert opinion to opinion of those actually on GFD
42%
35%
23%
Satisfaction with GFD
Sanders JGLD 2011

25. Why do we need non-dietary treatments for Celiac Disease?
The GFD is highly effective in celiac disease BUT:
> 10% Non-responsive to GFD
1 - 2% Refractory to GFD
~ 30% of adults on GFD for celiac disease have ongoing partial villous atrophy on biopsy
Strict GFD difficult to maintain
At social events
For food prepared outside the home
When travelling
In restaurants & cafeterias
Take-out
For the elderly
For the illiterate
For those with mental or psychological impairment
Sanders JGLD 2011

26. † VAS: 0 = Worst imaginable health 100 = Best imaginable health
Perceived overall health is
excellent in treated Celiac Disease
Overall Health
Visual Analog Scale
VAS †
78:
CD = Celiac disease
55.4
ESRD = Renal disease
on hemodialysis 78
72.4
76.7
71.6
69.9
70.5
57.8*
55.4*
CD 78 (16.7) ( )
GERD 71.6 (21.6) ( )
HTN 72.4 (20.9) ( )
IBD 76.7 (19.1) ( )
CHF 57.8 (21.2)( )
IBS 70.5 (18.1)( )
DM 69.9 (23)( )
ESRD 55.4 (17.8) ( )
† VAS: 0 = Worst imaginable health
100 = Best imaginable health
*Compared with CD, p<0.001
BIDMC Celiac Center 2013 – under review 26

27. † VAS: 0 = Very Easy 100 = Very Difficult
Perceived treatment burden
of GFD is very high
Treatment Burden
VAS †
Renal disease on
Hemodialysis = 56.4
Celiac disease = 44.9
Higher than:
Insulin dependant diabetes
Irritable bowel syndrome
Congestive heart failure
Inflammatory bowel disease
Hypertension
GERD
56.4
44.9
41.7
38.4
40.4
CD 44.9(30.9)
Gerd 21.3(25.3)
Htn 23.5(25.7)
IBD 31.9(27.7)
Chf 38.4(31)
Ibs 40.4(24.4)
Dm 41.7(30.4)
Esrd 56.4(31.9)
31.9
23.5*
21.3*
† VAS: 0 = Very Easy
100 = Very Difficult
*Compared with CD, p<0.001
BIDMC Celiac Center 2013 – under review 27

28. What’s New in Sprue International Celiac News
How common is celiac disease? A moving target
Why are so many people eating Gluten Free (and does it help me)?
News from BIDMC Celiac Center
Making gluten challenge less challenging
The burden of treating celiac disease - a difficult pill to swallow
Progress toward new treatments for celiac disease

29. Help on it’s way? Gluten is Everywhere “Wheat-free” ≠ “Gluten-free.”
Dressing
Flour or cereal products
Gravies
Imitation bacon
Imitation seafood
Lipstick and lip balm
Breading
Broth/Bouillon
Candy
Coating/Drink mixes
Communion wafers
Croutons
Marinades
Panko
Pastas
Play-Doh
Processed luncheon meats
Sauces
Dry pet food
Seasonings
Self-basting poultry
Soup bases
Thickeners (Roux)
Toothpaste
Dental pumice
Medications
Help on it’s way?
© 2008 Delete the Wheat

30. Larazotide acetate reduces symptoms during gluten challenge
86 study subjects
Gluten-Related Adverse Events
Placebo No challenge Larazotide
+ Challenge Challenge
Changes in symptom score during gluten challenge
Placebo
Larazotide
No gluten challenge
Leffler et al Am J Gastro. 2012;107:

31. Larazotide acetate prevents IgA tTG Increases during gluten challenge
Next study completed enrollment
>200 subjects
Continued symptoms & high tTG
Despite GFD
IgA-tTG (IgA-tissue Transglutaminase)
fold change from baseline (mean) 38 32 25 18 12 6
Gluten challenge
Placebo
Larazotide acetete:
8 mg three times daily
1 mg three times daily
4 mg three times daily
0.03
0.01
0.02
0.009
0.008
0.005
Day Last visit
Day 0
Day 7
Day 21
Day 35
Day 49
Day 56
LDBTPV
184 study subjects
Kelly et al Aliment Pharmacol Ther Jan;37(2):

32. What’s New in Sprue International Celiac News
How common is celiac disease? A moving target
Why are so many people eating Gluten Free (and does it help me)?
News from BIDMC Celiac Center
Making gluten challenge less challenging
The burden of treating celiac disease - a difficult pill to swallow
Progress toward new treatments for celiac disease
Getting fatter gluten free & why it’s good to have celiac disease

33. Mean BMI increased from 24.0 to 24.6
In 679 celiac patients:
At diagnosis: 32% overweight or obese (compared to 59% in regional population)
On GFD:
Mean BMI increased from 24.0 to 24.6
22% with normal or high BMI at diagnosis increased BMI by >2 points
15.8% became overweight
22% overweight at diagnosis gained additional weight
Attention to weight maintenance essential on GFD
Aliment Pharmacol Ther Mar;35(6):723-9.

34. Diabetes Mellitus Type 2 is far less common in Celiac disease
Pravelence of diabetes type 2
Celiac %
Control – % (x3 celiac rate)
Population - 9.8% (x3 celiac rate)
P <
(n = 840)
(n = 840)
BMI (Body Mass Index)

35. What’s New in Sprue International Celiac News
How common is celiac disease? A moving target
Why are so many people eating Gluten Free (and does it help me)?
News from BIDMC Celiac Center
Making gluten challenge less challenging
The burden of treating celiac disease - a difficult pill to swallow
Progress toward new treatments for celiac disease
Getting fat gluten free & why it’s good to have celiac disease
CeliacNow.org – Celiac disease & the GFD in digestible bytes
More Celiacologists come to Boston

36. What’s New in Sprue (near you)

37. Celiac disease prevalence - a moving target
CeliacNow.org
Level 1 – The basics
Level 2 – More detailed
Level 3 – In depth information

38. Celiac Research Groups in Boston
Boston Children’s Hospital – Director: Alan Leichtner, MD
BIDMC – Director: Ciaran Kelly, MD
& the new kids on the block:
MGH – Director: Alessio Fasano, MD
All Major Teaching Hospitals of Harvard Medical School
Collaborate in:
Research –
Education –
Fund raising –
Combined Groups:
~ 40 Celiac Researchers (MD, PhD, RD et al)
> 25 Celiac disease research publications in 2012
Current expenses ~$3 million per annum

39. What did he say? International Celiac News
Celiac disease is more common than ever
Non Celiac Gluten Sensitivity - a recognized medical entity
News from BIDMC Celiac Center
Gluten challenge (aka “GFD holiday”) less challenging
GFD considered burdensome by patients
New treatments for celiac disease – progress, but slow
GFD can make you look fat but at least you may avoid diabetes
CeliacNow.org for all your Gluten Free bytes
Boston abounds in Celiac Researchers – let’s keep us busy!