Coeliac disease. Questions and Controversies. Professor Andrew Day Paediatric Gastroenterology University of Otago, Christchurch

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1 Coeliac disease Questions and Controversies Professor Andrew Day Paediatric Gastroenterology University of Otago, Christchurch What is Coeliac disease? Is Coeliac disease the same as it ever was? How to diagnose Coeliac disease? Is there more than Coeliac disease? What can we learn for the future? 1

2 Case 1 4 year old boy Reports belly pains for last 6 months or so Occasional loose BM More pale Parents concerned about weight gains (poor) Looks slightly pale Case 1 Abdominal exam unremarkabe 2

3 Case 1 Hb 97, MCV 78 ttg 155, IgA normal Duodenum scalloped folds, mosaic, friable Patchy subtotal villous atrophy Case 2 14 months old 3 months symptoms Diarrhoea (increasing), bloated, pale, lethargic, grumpy (?pain), no weight gains 3

4 Case 2 Weight Pale, irritable, wasted, distension++ Iron deficient Anaemic (Hb 87) ttg 3 IgG AGA 176 SBB severe villous atrophy Coeliac Disease over 2 millennia. Aretaeus the Cappadocian 100 AD Koiliakos: meaning "suffering in the bowels." 4

5 Willem Dicke 1950s Coeliac Disease II: the presence in wheat of a factor having a deleterious effect in cases of coeliac disease Acta Paediatr 1953;42:34-42 Coeliac disease over time Fatal complications Corticosteroids Gluten free diet New tests 5

6 Normal small bowel Coeliac disease Normal diet GFD Pathogenesis of CD 6

7 Genes in Coeliac Disease DQ2 A1*0501-B1*0201: 95% DQ8 A1*0301-B1*0302: 3% a chromosome 6 1 Mb 1 Mb 2 Mb DPC4/C2/ TAP/LMP CYP21/Bf TNF/LT/BAT DP DM DQ DR HSP70 MIC B C E A G F Centromer Telomer Class II Class III Class I b DQB1 DQA1 DRB1 presented peptide DR3-DQ cis DR5-DQ7 DR7-DQ / trans β α HLA-DQ2 molecule Tye-Din, Cameron, Daveson, Day et al, IMJ

$Andropo- goneae SUBTRIBE Triticineae / \ GENUS Triticum Secale Hordeum Avena Oryza Zea SPECIES T.$

8 What is Gluten?? Storage protein of cereal seeds Glutinous properties of gluten make it useful to the food industry FAMILY Gluten and Grains Gramineae SUBFAMILY Festucoideae Panicoideae TRIBE Triticeae Aveneae Oryzeae Andropo- goneae SUBTRIBE Triticineae / \ GENUS Triticum Secale Hordeum Avena Oryza Zea SPECIES T.aestivum S.cereale H.vulgare A.sativa O.sativa Z.mays (WHEAT) (RYE) (BARLEY) (OAT) (RICE) (CORN) 8

9 Is Coeliac Disease more common? :5000 9

10 1994 1: Prevalence 1:100 COELIAC DISEASE Fasano A et al. Arch Intern Med 2003; 163: Talley NJ et al. Am J Gastroenterol 1994; 89: Coeliac disease becoming more common in Finland : 1.03% : 1.99% 2010: 2.4% Lohi et al, APT, 2007 Mustalahti et al, Ann Med

11 Increasing rates in USA 5% Highest rates in world to date. 11

12 Coeliac disease in countries where thought not to occur How about NZ? 12

13 CD in NZ Otago (1987) 9/100,000 Wellington (1992) 70/100,000 ChCh (1996) 1200/100,000 (1.2%) Cook et al. J Gastro Hep 2000 Ussher et al, NZMJ, 1994 Carrington et al, NZMJ, 1987 CD in ChCh Cook et al. NZMJ

14 Increasing Diagnoses/Year Why more Coeliac disease? Changing diet More gluten exposure Different food processing methods Infant feeding practices Role of infections/bacteria More Recognition? 14

15 Swedish Epidemic Ivarsson et al, 2000 Where do we find Coeliac disease? 15

16 Where s Wally? 16

17 17

18 Coeliac disease has wide and diverse features. 18

Coeliac iceberg Maki and Pekka. Lancet 1997; 349: 1755-59.

19 Coeliac iceberg Maki and Pekka. Lancet 1997; 349: Range of CD Presentations short-stature anaemia/fe deficiency chronic abdo pain failure to thrive mouth ulcers / stomatitis rickets constipation NO SYMPTOMS AT ALL 19

20 ChCh Coeliac Disease: Symptoms 0-5 yrs: Diarrhoea 51.5% Failure to thrive 46% 5-12 yrs: Pain 60% yrs: Pain 46% ChCh Coeliac Disease: Risks Family history 96 (36%) Diabetes 24 (9%) Down Syndrome 14 (5%) Asymptomatic (screening) 40 (15%) 20

21 Median age at diagnosis Age Age of new members, Coeliac Society Victoria (Courtesy CSV). Coeliac Disease Associations IgA deficiency Type 1 Diabetes Mellitus Downs Syndrome Atopic Dermatitis Inflammatory Bowel Disease Thyroiditis Hepatitis Epilepsy (with cerebellar calcifications) Cystic fibrosis Family History 21

22 Looking for Coeliac disease How can we find it?? Finding Coeliac disease Growth Retardation Bulky Fatty Feces fecal-fat antigliadin EMA (ttg) 2000-today DQ2/8; ttg Myo9B etc, others??? Find a scope and biopsy!!! 22

23 How is coeliac disease diagnosed? Someone has to suspect it! A blood test suggests it EMA / ttg (IgA, Hb, Fe, IgG-based assay) A duodenal biopsy confirms the diagnosis 23

24 Prevention in High Risk Infants Previous: Gluten 4-6 months + BF Now: timing relevant, BF less important Is there more than Coeliac disease? 24

25 25

26 Advice Naturopath/ Other Coeliac disease People purchasing gluten-free food Gluten allergy? Fructose malabsorption 916 children 1% diagnosed with CD 5% avoided gluten Predictor for gluten avoidance = Christchurch location (OR 2.2) 26

27 Gluten exposure in IBS Gluten exposure lead to symptoms in adults with IBS. 34 included Randomised controlled bread/muffins Symptoms in 1 week No change in tests Biesiekierski et al. Am J Gastroenterol

28 Responses to other components? Wherever gluten is found, other substances that can cause gastrointestinal symptoms are also found Most commonly fructans but also other poorly absorbed carbohydrates Restricting gluten also restricts these and may improve symptoms Biesiekierski et al. J Hum Nutr Diet 2011 Colon Small bowel FODMAPs Luminal distension gas fluid Bloating Diarrhoea Wind Pain 28

29 In the coming years.. Diagnostic Approaches Clarity about non-coeliac conditions GF products New treatment options Future treatments 29

30 A cure??? 30

31 31

32 Oats and a bit of wheat 32

Kristin Kenrick, FRNZCGP Department of General Practice and Rural Health Dunedin School of Medicine (Supported by Coeliac New Zealand)

Kristin Kenrick, FRNZCGP Department of General Practice and Rural Health Dunedin School of Medicine (Supported by Coeliac New Zealand) That you will go away thinking about your practice population, and