Celiac Disease in Children

8/3/2019 Celiac Disease in Children

1/45

Celiac Disease in Children:

The Calgary Clinic Data

Calgary Celiac Disease Conference

25 October 2008

J. Decker Butzner, MD, FRCPC

Head , Division of Pediatric GastroenterologyAlberta Childrens Hospital,

Professor, University of Calgary

1


2/45

Disclosures

Member Professional Advisory Board

Canadian Celiac Association

Member Professional Advisory Board

Canadian Celiac Association Calgary

Chapter

Financial Disclosures - Nil

2


3/45

Objectives Provide an update on the genetics and

pathophysiology of celiac disease

Southern Alberta data on celiac disease inchildren

Diagnosis

Follow up

Compare to Canadian Pediatric Celiac Survey

from 2002

3


4/45

Definition Celiac disease is an autoimmune condition

Occurs in genetically susceptible individuals

DQ2 and/or DQ8 positive HLA haplotype is necessary butnot sufficient

A unique autoimmune disorder because:

both the environmental trigger (gluten) and the autoantigen

(tissue Transglutaminase) are known

elimination of the environmental trigger leads to a completeresolution of the disease

4


5/45

Risk Factors

The Grains

The Genes

Celiac disease is not just a

disease of Caucasians 5


6/45

Dietary Factors

FestucoideaeSubfamily

Tribe

Zizaneae Oryzeae Hordeae Aveneae Festuceaea Chlorideae

wild rice rice wheat oat finger millet teff

(ragi)

rye

barley

The Grass Family - (GRAMINEAE)

6


7/45

Multiple genes involved

The most consistent genetic component

depends on the presence of HLA-DQ

(DQ2 and / or DQ8) genes DQ2 or DQ8 found in 99% of celiac patients

DQ2 or DQ8 found in 40% of the general

population

HLA-DQ2 and / or DQ8 genes are necessary

(No DQ2/8, no Celiac Disease!) but not sufficient

for the development of the disease

Other genes (not yet identified) account for 60 %

of the inherited component of the disease

HLA

?? ?

?

Gluten

Celiac Disease

+

GenesGenetics

7


8/45

Pathogenesis

Celiac disease

GlutenNecessary

Causes

GenderInfant feeding

Infections

Others

Risk Factors

Pathogenesis

?

Genetics

8


9/45

9

Normal small bowelNormal small bowel Celiac diseaseCeliac disease

Gluten

Gluten-free diet


10/45

APC

Submucosa

TTG

T

Intestinal lumen

10


11/45

Intestinal Lumen

Submucosa

TTG

T APC

11


12/45

Intestinal lumen

Submucosa

T

BAGA, EMA,

ETTG

Cytokines (IL-15)Tk

P APC

12


13/45

Classic Celiac Disease

13


14/45

Gastrointestinal Manifestations

(Nonclassic)

Irritable bowel syndrome C & D types

Chronic diarrhea without weight loss

Abdominal pain

Vomiting

Constipation

14


15/45

Non Gastrointestinal

Manifestations

Dermatitis Herpetiformis

Iron-deficiency anemiaresistant to oral Fe

Dental enamel hypoplasia

of permanent teeth

Osteopenia/Osteoporosis

Short Stature

Delayed Puberty

Elevated transaminases

Arthritis Neurological

- Epilepsy with occipital

calcifications

- Ataxia- Peripheral neuropathy

Infertility

Most common age of presentation: older child to adult

15


16/45

Associated Conditions

Relatives IDDM Thyroiditis Down

syndrome

0

4

8

12

16

20

percentage

General

Population

16


17/45

ACH Celiac Disease Database

Create a database to examine incidence,primary symptoms, mode of presentation,associated diseases and family history inchildren diagnosed at ACH since 1990

Compare the prescreening era (1990 1996)to the screening era (2000 2006)

Collect prospective data on adherence to agluten-free diet, ongoing health issues,quality of life in children with long standingceliac disease

17


18/45

Children Diagnosed with Celiac Disease at

Alberta Childrens Hospital

_______Pre-screening_____ _________Screening________

266 children

61% female

Median age at Dx 8 yrs

18


19/45

Comparison of Pre Screening Era to the

Screening Era in Calgary Clinic

Pre-screening

(1990-96)

Screening

(2000-06)

Patients, n 36 199

Female:male 1.6:1 1.6:1

Median age at

diagnosis (yrs)

2 9

p


20/45

Clinical Presentations 1990 - 2006

Symptom or

Condition

Pre-screening n=36

(1990-96)

n (%)

Screening n=199

(2000-06)

n (%)

Family History 0 35 (17.6)

Abdominal Pain +Other * 5 (13.9) 34 (17.1)

Abdominal Pain Only 0 18 (9.0)

Type 1 Diabetes 2 (5.6) 14 (7.0)

Failure to Thrive ** 1 (2.8) 13 (6.5)

Endoscopy for Other 0 8 (4.0)

Chronic Diarrhea 1 (2.8) 7 (3.5)

Short Stature 0 6 (3.0)

Fe Deficiency sAnemia 1 (2.8) 6 (3.0)

Trisomy 21 0 5 (2.5)

Constipation 0 5 (2.5)

Vomiting 1 (2.8) 2 (1.0)

Dermatitis Herpetiformis 0 2 (1.0)

Food Allergy 0 1 (0.5)

Abdominal Distention 0 1 (0.5)

Elevated Transaminases 0 1 (0.5)

Hypothyroidism 0 1 (0.5)

Dental Enamel Defects 0 1 (0.5)

Hypoalbuminemia 1 (2.8) 0

Classic celiac 24 (67) 39 (20)

* Symptoms or conditions

** No GI symptoms

Blood in stool, reflux

No weight loss or FTT

20


21/45

Distribution of Patients by Presentation and

Gender after Introduction of Screening

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

< 3 3 - 9 10 - 17 . Female Male

Age (years)

Patients(

Classic Celiac GI Symptoms Extra-intestinal Silent

n = 30 n = 82 n = 87 n = 123 n = 86 21

2000 - 2006


22/45

Conclusions: Impact of screening on the

Calgary Clinic

Screening tripled the incidence and quadrupled the

median age at diagnosis of celiac disease in children

The classic celiac presentation remains common (67%) in

younger children (


23/45

Childhood Celiac Health Surveys: Calgary

Clinic & Canada

Follow up of individuals with celiac disease

diagnosed in childhood

Calgary Clinic includes children from Southern

Alberta and SE British Columbia Children

Canadian data includes follow up children whoare members of the CCA across the country

Calgary data (n = 146); Canada data (n = 168)

23


24/45

Questionnaire sent to 267 children who werediagnosed with celiac disease from 1990 2006

45 were undeliverable

146/222 respondents (66%)

Time since diagnosis 2.5 yr (range .5 17 years)

62 on diet < 2 years41 on diet 2 5 years

43 on diet > 5 years

Methods Calgary Clinic Childrens Survey

24


25/45

Calgary Clinic Pediatric Survey Data

CalgaryN = 146

Median age of

participants

11 yrs

Age range participants 1 31 yrs% Female 61%

Median age at Dx 8 yrs

Age range at Dx 1 17 yrs

Member of CCA 58%

25


26/45

Are Asymptomatic Children Really

Asymptomatic?

125 symptomatic and 21 asymptomatic

Family hx (15), Type-1-diabetes (4), thyroid (2)

14 / 21 asymptomatic reported improvement in 1 or

more symptoms after starting GFD

Fatigue 57%, abdo pain 43%, nausea 36%, bloating 36%

Health improved: a lot 22%, somewhat 64%,

not at all/ worse 14%

React to gluten: always 29%, sometimes 24%,

rarely / never 47%

Many asymptomatic children retrospectively report

symptoms that improve on a GFD and react to gluten26


27/45

Follow up of family members after

diagnosis Calgary study

First degree relatives screened

All 37%, Some 41%, None 22%

Second degree relatives screened

Yes 38%, No 62%

Family members diagnosed with celiac

disease Yes, before my Dx 25%

Yes, after my Dx 17%

No 58%27


28/45

Follow up of family members after

diagnosis Calgary study

Family members starting GFD without biopsy

Yes 17%, No 81%

My family eats gluten and I eat GFDAll/Most of time 57%, Some of time 37%, Never 5%

My family reads labels to determine GF foods

All/Most of time 94%, Some of time 3%, Never 2%

I participate in determining if my food is GF Always 38%, daily 34%, weekly 15%, monthly 8%, never 15%

28


29/45

Canadian Pediatric Celiac Health

Survey

Mohsin Rashid, Anne Cranney, Marion Zarkadas, Connie

Switzer, Ian D. Graham, Shelly Case, Mavis Molloy, Ralph

Warren, Vern Burrows, J Decker Butzner

Pediatrics Dec 2005;116:e754-759

29


30/45

Questionnaire sent to all members of the Canadian

Celiac Association (n=5,240) in 2002

3,048 respondents (65%)

194 children (


31/45

Comparison of Calgary Clinic &

Canadian Pediatric Survey DataCalgary Canada

N = 146 168

Median age of

participants

11 yrs 9 yrs

Age range participants 1 31 yrs 2 15 yrs

% Female 61% 58%

Median age at Dx 8 yrs 3 yrsAge range at Dx 1 17 yrs 1 15 yrs

Member of CCA 58% 100% by def.

31


32/45

Comparison of Calgary Clinic &

Canadian Pediatric Survey Data

Reaction after accidental ingestion of gluten

Calgary Canada

% with reaction 61% 54%

Abdominal pain 87% 87%Diarrhea 67% 64%

Bloating 71% 57%

Fatigue 51% 37%

Headache 29% 24%

Median time to Sx 2hrs 2 hrs

Time range to Sx 15 min 48 hr 20 min 60 hr

Most displayed more than one symptom during a reaction32


33/45

All or Most Some of Never

of the time the time

(%) (%) (%) (%) (%) (%)

Avoided restaurants 39 54 41 41 20 5 Avoided traveling 3 15 23 31 75 54

Found it difficult to find 12 28 63 62 24 10gluten-free foods at stores

Found it difficult to determine if 3 27 63 65 34 8the food was gluten-free

Felt that they were not invited out 3 10 25 35 72 53for meals due to celiac disease

Celiac Health Surveys: Calgary & CanadaCalgary data (n = 146); Canada data (n = 168)

33


34/45

All or Most Some of Never

of the time the time

(%) (%) (%) (%) (%) (%)

Felt left out of activities at 8 13 38 48 54 37school or friends homes

Felt different from other kids 20 18 48 51 30 29

because of celiac disease

Felt embarrassed to bring 9 23 34 30 56 45

gluten-free foods to parties

Felt angry about having to follow 15 23 41 49 41 26

a special diet

Felt they can be healthy without 4 4 21 22 74 71

following a special diet

Celiac Health Surveys: Calgary & CanadaCalgary data (n = 146); Canada data (n = 168)

34


35/45

Gluten Ingestion in Children in Calgary Clinic

N = 146 < 1 time

/year

1-3 times

/year

1-3 times

/month

1-3 times

/week

Daily Missing

Accidental 20% 50% 23% 3% 2% 2%

Intentional 64% 13% 13% 4% 4% 2%

Reasons

No reaction to gluten 10%, No effect on health 8%

Difficult to determine if Gluten Free 26%, Hidden gluten 41%

Difficult to order GF meal 32%, Do not like taste of GF 10%

Feel different 14%, Angry about CD 11%,

No GF prep in home 3%

35


36/45

Gluten ingestion: Risk factors in Calgary Clinic

Children with poor

compliance displayed:

Increasing age

40% >18yo, 29% 13-17 yo,

21% 9-12yo, 7% 5-8yo

Time since diagnosis

40% >5yrs, 15% 2-5 yrs,

13%


37/45

Conclusions

Celiac Health Surveys: Pediatric Data

Calgary and Canadian data generally similar

Children with celiac disease can present with a

variety of symptoms Many have had other diagnoses prior to that of celiac

disease and delays in diagnosis are common

While most adjust well, 10 to 20% continue to have

significant difficulties in modifying their lifestyles

Many asymptomatic children retrospectively report

symptoms that improve on a GFD and react to gluten

37


38/45

Acknowledgements

Summer students Calgary Celiac Assoc

Derek Castiglione Karen RenaudKelly E. McGowan

Secretaries

Tanya Fillion

Supported by grants from the Calgary Chapter of the

Canadian Celiac Assoc, the University of Calgary and the

Canadian Association of Gastroenterology.

38


39/45

Other diagnoses prior to the diagnosis

of celiac disease

Canadian Celiac Health Survey:

Pediatric data (n=168)

%

Anemia 15

Irritable bowel syndrome 11

Gastroesophageal reflux 8Stress 8

Stomach ulcer 4

39


40/45

Physician consulted before the

diagnosis of celiac disease confirmed



24% consulted 2 family physicians

30% consulted 2 pediatricians

6% consulted 2 gastroenterologists

Average time from development of symptoms

to diagnosis = 1 year

40


41/45

%

Abdominal pain 90

Weight loss 71

Poor growth 70

Diarrhea 65Extreme weakness64

Nausea, vomiting 53

Anemia 40

%

Mood swings/depression37

Constipation 30

Eczema 24

Bone/joint pain 21Mouth ulcers 16

Muscle cramps 14

Easy bruising 11

Clinical symptoms prior to diagnosis of

celiac disease



41


42/45

ACH Celiac Disease Database

Number of Cases Diagnosed

0

20

40

60

80

100

120

140

160

180200

1990-1995 1996-2000 2001-2006

Year

#

ofcases

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%70.0%

Percentage

ofyears

total#

ofcases

Number Per cent with Classic CD

42


43/45

Short Stature/Delayed Puberty Short stature in children / teens:

y b10% of short children and teens have

evidence of celiac disease Delayed menarche:

y Higher prevalence in teens with untreated

celiac disease

43


44/45

Why talk about celiac disease?

Celiac disease affects between 1 in 100 and1 in 300 North Americans

Only 1 in 5 present with classic symptoms It takes an average of 11 years from the

onset of symptoms to make the diagnosisCanadian data 2,681 patients

37 % of patients saw 2 or more physiciansprior to diagnosis

Celiac disease has many atypicalpresentations

44


45/45

WHO criteria for disease

screening Disease causes serious health problems

Screening test should be reliable (few false

negatives and false positives) for the targetdisease

A treatment for the disease must be available

If not recognized in time, the disease could

result in difficult to manage complications

45

Celiac Disease in Children

Documents

Transcript of Celiac Disease in Children