Celiac Disease in Children: The Calgary Clinic Data

1
Celiac Disease in ChildrenThe Calgary Clinic
Data

• Calgary Celiac Disease Conference
• 25 October 2008
• J. Decker Butzner, MD, FRCPC
• Head , Division of Pediatric Gastroenterology
• Alberta Childrens Hospital,
• Professor, University of Calgary

2
Disclosures

• Member Professional Advisory Board Canadian
  Celiac Association
• Member Professional Advisory Board Canadian
  Celiac Association Calgary Chapter
• Financial Disclosures - Nil

3
Objectives

• Provide an update on the genetics and
  pathophysiology of celiac disease
• Southern Alberta data on celiac disease in
  children
• Diagnosis
• Follow up
• Compare to Canadian Pediatric Celiac Survey from
  2002

4
Definition

• Celiac disease is an autoimmune condition
• Occurs in genetically susceptible individuals
• DQ2 and/or DQ8 positive HLA haplotype is
  necessary but not 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 complete resolution of the disease

5
Risk Factors
The Grains
The Genes
Celiac disease is not just a disease of
Caucasians
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Dietary Factors
The Grass Family - (GRAMINEAE)
Subfamily Tribe
Festucoideae
Zizaneae Oryzeae Hordeae
Aveneae Festuceaea Chlorideae
wild rice rice wheat oat
finger millet teff
(ragi)
rye barley
7
Genetics

• 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

Genes
?
?
?
HLA
?

Gluten
Celiac Disease
8
Pathogenesis
Necessary Causes
Gluten
Genetics
Gender Infant feeding Infections Others
Pathogenesis ?
Risk Factors
Celiac disease
9
Normal small bowel
Celiac disease
Gluten
Gluten-free diet
10
Intestinal lumen
TTG
APC
T
Submucosa
11
Intestinal Lumen
TTG
APC
T
Submucosa
12
Intestinal lumen
Cytokines (IL-15)
Tk
APC
P
T
AGA, EMA, aTTG
B
Submucosa
13
Classic Celiac Disease
14
Gastrointestinal Manifestations(Nonclassic)

• Irritable bowel syndrome C D types
• Chronic diarrhea without weight loss
• Abdominal pain
• Vomiting
• Constipation

15
Non Gastrointestinal Manifestations
Most common age of presentation older child to
adult

• Dermatitis Herpetiformis
• Iron-deficiency anemia
• resistant 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

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Associated Conditions
20
16
12
percentage
8
4
General Population
0
Relatives
IDDM
Thyroiditis
Down syndrome
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ACH Celiac Disease Database

• Create a database to examine incidence, primary
  symptoms, mode of presentation, associated
  diseases and family history in children diagnosed
  at ACH since 1990
• Compare the prescreening era (1990 1996) to the
  screening era (2000 2006)
• Collect prospective data on adherence to a
  gluten-free diet, ongoing health issues, quality
  of life in children with long standing celiac
  disease

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Children Diagnosed with Celiac Disease at Alberta
Childrens Hospital
266 children 61 female Median age at Dx 8 yrs
_______Pre-screening_____
_________Screening________
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Comparison of Pre Screening Era to the
Screening Era in Calgary Clinic
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Clinical Presentations 1990 - 2006

• Symptoms or conditions
• No GI symptoms
• Blood in stool, reflux
• No weight loss or FTT

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Distribution of Patients by Presentation and
Gender after Introduction of Screening
2000 - 2006
n 30 n 82 n 87
n 123 n 86
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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 (lt3 yr old), while
  atypical presentations are frequently observed
  in older children
• 12 new clinical presentations observed in 42 of
  children in the screening group
• Gastrointestinal symptoms still predominate the
  clinical presentation, but they are increasingly
  diverse
• Currently, one quarter of children are diagnosed
  due to family history or a celiac-associated
  condition

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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 who are
  members of the CCA across the country
• Calgary data (n 146) Canada data (n 168)

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Methods Calgary Clinic Childrens Survey

• Questionnaire sent to 267 children who were
  diagnosed 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 lt 2 years
• 41 on diet 2 5 years
• 43 on diet gt 5 years

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Calgary Clinic Pediatric Survey Data
26
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 gluten

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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

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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 GFD
• All/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

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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 2005116e754-759
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Methods Canadian Survey Data on presentation of
celiac disease

• Questionnaire sent to all members of the
  Canadian Celiac Association (n5,240)
  in 2002
• 3,048 respondents (65)
• 194 children (lt16 years)
• 168 children had biopsy-confirmed celiac disease

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Comparison of Calgary Clinic Canadian Pediatric
Survey Data
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Comparison of Calgary Clinic Canadian Pediatric
Survey Data
Reaction after accidental ingestion of gluten
Most displayed more than one symptom during a
reaction
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Celiac Health Surveys Calgary Canada Calgary
data (n 146) Canada data (n 168)

• 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 10
• gluten-free foods at stores
• Found it difficult to determine if 3 27
  63 65 34 8
• the food was gluten-free
• Felt that they were not invited out 3 10 25
  35 72 53
• for meals due to celiac disease

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Celiac Health Surveys Calgary Canada Calgary
data (n 146) Canada data (n 168)

• All or Most Some of Never of the
  time the time () () ()
  () () ()
• Felt left out of activities at 8 13
  38 48 54 37
• school 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

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Gluten Ingestion in Children in Calgary Clinic
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
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Gluten ingestion Risk factors in Calgary Clinic

• Children with poor compliance displayed
• Increasing age
• 40 gt18yo, 29 13-17 yo,
• 21 9-12yo, 7 5-8yo
• Time since diagnosis
• 40 gt5yrs, 15 2-5 yrs, 13 lt2yrs since
  diagnosis
• Reaction to gluten
• 23 no/rare reaction
• 33 sometimes reaction
• 12 always reaction
• No medical follow up for celiac disease 38
• Medical follow up 15

• No effect on compliance
• Age at diagnosis
• Sex of child
• Asymptomatic at diagnosis
• Membership in Canadian Celiac Assoc

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Celiac Health Surveys Pediatric Data

Conclusions

• 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

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Acknowledgements
Summer students Calgary Celiac Assoc Derek
Castiglione Karen Renaud Kelly 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.
39
Canadian Celiac Health Survey Pediatric data
(n168)
Other diagnoses prior to the diagnosis of celiac
disease
Anemia 15 Irritable bowel syndrome 11
Gastroesophageal reflux 8 Stress 8
Stomach ulcer 4
40
Canadian Celiac Health Survey Pediatric data
(n168)
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
41
Canadian Celiac Health Survey Pediatric data
(n168)
Clinical symptoms prior to diagnosis of celiac
disease
Abdominal pain 90 Weight loss 71 Poor
growth 70 Diarrhea 65 Extreme
weakness 64 Nausea, vomiting 53 Anemia 40
Mood swings/depression 37 Constipation
30 Eczema 24 Bone/joint pain 21 Mouth
ulcers 16 Muscle cramps 14 Easy bruising 11
42
ACH Celiac Disease Database
43
Short Stature/Delayed Puberty

• Short stature in children / teens
• ? 10 of short children and teens have
  evidence of celiac disease
• Delayed menarche
• ? Higher prevalence in teens with untreated
  celiac disease

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Why talk about celiac disease?

• Celiac disease affects between 1 in 100 and 1 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 diagnosis Canadian data
  2,681 patients
• 37 of patients saw 2 or more physicians prior
  to diagnosis
• Celiac disease has many atypical presentations

45
WHO criteria for disease screening

• Disease causes serious health problems
• Screening test should be reliable (few false
  negatives and false positives) for the target
  disease
• A treatment for the disease must be available
• If not recognized in time, the disease could
  result in difficult to manage complications