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2/09/15 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?

ASD Coeliac GDA 2015 FINAL - Otago

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Page 1: ASD Coeliac GDA 2015 FINAL - Otago

2/09/15

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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?

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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)

Case 1

Looks slightly pale Abdominal exam unremarkabe

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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

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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."

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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

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Normal small bowel Coeliac disease

Normal diet

GFD

Pathogenesis of CD

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b

a

0201 0501 0301DR3-DQ2 cis

0301 0505 11/12DR5-DQ7

0202 0201 07 trans

DR7-DQ2 HLA-DQ2 molecule

β α

presented peptideDQB1 DRB1DQA1

Centromer

DP

TAP/LMPDPC4/C2/CYP21/Bf

HSP70 MIC

TNF/LT/BAT

B C E A G FDM DQ DR

Telomer

Class II Class III Class I

2 Mb1 Mb1 Mb

b

a

0201 0501 0301DR3-DQ2 cis

0301 0505 11/12DR5-DQ7

0202 0201 07 trans

DR7-DQ2 HLA-DQ2 molecule

β α

presented peptideDQB1 DRB1DQA1

Centromer

DP

TAP/LMPDPC4/C2/CYP21/Bf

HSP70 MIC

TNF/LT/BAT

B C E A G FDM DQ DR

Telomer

Class II Class III Class I

2 Mb1 Mb1 Mb

DQ2 A1*0501-B1*0201: 95% DQ8 A1*0301-B1*0302: 3%

chromosome 6

Genes in Coeliac Disease

Tye-Din, Cameron, Daveson, Day et al, IMJ 2015

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What is Gluten??

Storage protein of cereal seeds

Glutinous properties of

gluten make it useful to the food industry

FAMILY 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)

Gluten and Grains

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Is Coeliac Disease more common?

1994 1:5000

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Fasano A et al. Arch Intern Med 2003; 163: 286-92. Talley NJ et al. Am J Gastroenterol 1994; 89: 843-46.

2003

Prevalence 1:100

COELIAC DISEASE

1994 1:5000

Coeliac disease becoming more common in Finland

1978-80: 1.03% 2000-01: 1.99% 2010: 2.4%

Lohi et al, APT, 2007 Mustalahti et al, Ann Med 2010

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Increasing rates in USA

5% Highest rates in world to date….

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Coeliac disease in countries where thought not to occur……

How about NZ?

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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 1970-99

Cook et al. NZMJ 2004

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0

5

10

15

20

25

30

35

40

1975 1980 1985 1990 1995 2000 2005 2010

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?

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Ivarsson et al, 2000

Swedish Epidemic

Where do we find Coeliac disease?

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Where’s Wally?

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Coeliac disease has wide and diverse features…….

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Coeliac iceberg

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

Range of CD Presentations

short-stature anaemia/Fe deficiency chronic abdo pain failure to thrive mouth ulcers / stomatitis rickets constipation NO SYMPTOMS AT ALL

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ChCh Coeliac Disease: Symptoms

0-5 yrs: Diarrhoea 51.5%

Failure to thrive 46% 5-12 yrs: Pain 60% 12-16 yrs: Pain 46%

ChCh Coeliac Disease: Risks Family history 96 (36%) Diabetes 24 (9%) Down Syndrome 14 (5%) Asymptomatic (screening) 40 (15%)

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0

10

20

30

40

50

60

70

80

90

1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73 77 81 85 89

Age

Numbe

r

Age of new members, Coeliac Society Victoria 2003. (Courtesy CSV).

Median age at diagnosis

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

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Looking for Coeliac disease How can we find it??

Finding Coeliac disease 1900-1950 Growth Retardation

Bulky Fatty Feces 1950-1970 fecal-fat 1980-1990 antigliadin 1990-2000 EMA (tTg) 2000-today DQ2/8; tTg 2011-2015 Myo9B etc, others???

Find a scope and biopsy !!!

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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

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Prevention in High Risk Infants

Previous: Gluten 4-6 months + BF Now: timing relevant, BF less important

Is there more than Coeliac disease?

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People purchasing gluten-free food

Gluten allergy? Fructose malabsorption

Advice Naturopath/Other

Coeliac disease

916 children

1% diagnosed with CD

5% avoided gluten

Predictor for gluten avoidance = Christchurch location (OR 2.2)

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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 2011

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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

Small bowel

Colon

Bloating Diarrhoea Wind Pain

FODMAPs

Luminal distension gas

fluid

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In the coming years…..

Diagnostic Approaches Clarity about non-Coeliac conditions GF products New treatment options

Future treatments

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A cure???

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Oats and a bit of wheat