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

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

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

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 2

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

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

5 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 % (half diagnosed) % (quarter diagnosed) Where is celiac disease most common? 5

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

7  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 Celiac disease An expanded perspective 7

8 Celiac disease now more common in the US? Or just more commonly diagnosed? Rubio-Tapia A et al. Gastroenterol 2009;137: Lohi S et al. Aliment Pharmacol Ther 2007;26: Then: 9,133 healthy young adults at Warren Air Force Base 1950: Blood collected (1948 to 1954) 0.2% with CD (positive TTG) 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 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)

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

10 Why is celiac disease more common? 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 “An idle immune system is the devil’s playground” 10

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) ? 11

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

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

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 14

15 Similar & significant differences for: Abdominal pain, bloating, tiredness & satisfaction with stool consistency Non-celiac gluten sensitivity 1.NCGS is a real phenomenon 2.Celiac disease cannot be diagnosed by a GFD trial

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

17 Celiac disease NCGS 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 Celiac disease versus NCGS (Non-celiac gluten sensitivity) 17

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 18

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 19

20 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 20

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

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

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 23

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 Sanders JGLD 2011 Satisfaction with GFD 35%23%42% 24

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 Sanders JGLD 2011 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 25

26 Overall Health † VAS: 0 = Worst imaginable health 100 = Best imaginable health * * *Compared with CD, p<0.001 Visual Analog Scale VAS † 78: CD = Celiac disease 55.4 ESRD = Renal disease on hemodialysis Perceived overall health is excellent in treated Celiac Disease BIDMC Celiac Center 2013 – under review 26

27 Treatment Burden † VAS: 0 = Very Easy 100 = Very Difficult * 21.3* *Compared with CD, p<0.001 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 Perceived treatment burden of GFD is very high VAS † 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 28

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

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

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

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 32

33 Aliment Pharmacol Ther Mar;35(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 % 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 33

34 Diabetes Mellitus Type 2 is far less common in Celiac disease BMI (Body Mass Index) Pravelence of diabetes type 2 Celiac - 3.1% Control – 9.6% (x3 celiac rate) Population - 9.8% (x3 celiac rate) P < (n = 840) 34

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 35

36 What’s New in Sprue (near you) 36

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

38 Boston Children’s Hospital – Director: Alan Leichtner, MD BIDMC – Director: Ciaran Kelly, MD & the new kids on the block: MGH – Director: Alessio Fasano, MD Celiac Research Groups in Boston 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 38

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! 39


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