Celiac Disease in Children: The Calgary Clinic Data

Calgary Celiac Disease Conference 25 October 2008
J. Decker Butzner, MD, FRCPC
Head , Division of Pediatric Gastroenterology Alberta Children¶s Hospital, Professor, University of Calgary
1

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

2

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
3

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

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Risk Factors The Grains The Genes Celiac disease is not just a disease of Caucasians 5 .

Dietary Factors The Grass Family .(GRAMINEAE) Subfamily Festucoideae Tribe Zizaneae Oryzeae Hordeae Aveneae Festuceaea Chlorideae wild rice rice wheat oat finger millet (ragi) teff rye barley 6 .

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 7 Genes ? ? ? ? HLA + Gluten Celiac Disease .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.

Pathogenesis Genetics Gluten Necessary Causes Gender Infant feeding Infections Others Pathogenesis ? Risk Factors Celiac disease 8 .

Normal small bowel Celiac disease Gluten Gluten-free diet 9 .

Intestinal lumen TTG T APC Submucosa 10 .

Intestinal Lumen TTG APC T Submucosa 11 .

EMA. ETTG B Cytokines (IL-15) APC Submucosa 12 .Intestinal lumen Tk P T AGA.

³Classic´ Celiac Disease 13 .

Gastrointestinal Manifestations (³Nonclassic´) ‡ ‡ ‡ ‡ ‡ Irritable bowel syndrome ± C & D types Chronic diarrhea without weight loss Abdominal pain Vomiting Constipation 14 .

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 .Ataxia .Peripheral neuropathy Infertility 15 ‡ .Epilepsy with occipital calcifications .

Associated Conditions 20 16 percentage 12 8 4 0 Relatives IDDM Thyroiditis Down syndrome 16 General Population .

quality of life in children with long standing celiac disease 17 . mode of presentation.ACH Celiac Disease Database ‡ Create a database to examine incidence. ongoing health issues. 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. primary symptoms.

Children Diagnosed with Celiac Disease at Alberta Childrens¶ Hospital 266 children 61% female Median age at Dx 8 yrs _______Pre-screening_____ _________Screening________ 18 .

n Female:male Median age at diagnosis (yrs) Incidence (/100.154 Patients.000/yr) Incidence classic celiac disease (/100.0 0.6:1 9 p<0.001 7.6 p=0.3 p<0.03 1.8 1.000/yr) 19 .6:1 2 2.Comparison of Pre ± Screening Era to the Screening Era in Calgary Clinic Pre-screening Screening (1990-96) (2000-06) 36 199 1.

5) 8 (4.0) 7 (3.0) 13 (6.5) 2 (1.8) 0 0 1 (2.Clinical Presentations 1990 .0) 5 (2.0) 14 (7.5) 0 39 (20) 20 .1) 18 (9.0) 6 (3.5) 5 (2.8) 0 1 (2.8) 0 1 (2.0) 1 (0.8) 0 0 0 0 0 0 1 (2.5) 1 (0.5) 6 (3.9) 0 2 (5.5) 1 (0.2006 Symptom or Condition Family History * Symptoms or conditions ** No GI symptoms ‚ Blood in stool. reflux Á No weight loss or FTT Abdominal Pain +Other * Abdominal Pain Only Type 1 Diabetes Failure to Thrive ** Endoscopy for Other ‚ Chronic Diarrhea Á Short Stature Fe Deficiency sAnemia Trisomy 21 Constipation Vomiting Dermatitis Herpetiformis Food Allergy Abdominal Distention Elevated Transaminases Hypothyroidism Dental Enamel Defects Hypoalbuminemia Classic celiac Pre-screening n=36 Screening n=199 (2000-06) (1990-96) n (%) n (%) 0 5 (13.5) 1 (0.6) 1 (2.0) 2 (1.5) 1 (0.8) 24 (67) 35 (17.6) 34 (17.

17 .2006 100% 90% 80% 70% P tie ts(% a n ) 60% 50% 40% 30% 20% 10% 0% < 3 3 . Female Male Age (years) n = 30 n = 82 n = 87 n = 123 n = 86 21 .9 10 .Distribution of Patients by Presentation and Gender after Introduction of Screening Classic Celiac GI Symptoms Extra-intestinal Silent 2000 .

one quarter of children are diagnosed due to family history or a celiac-associated condition 22 . but they are increasingly diverse ‡ Currently. while ³atypical´ 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.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 (<3 yr old).

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) 23 .

5 ± 17 years) 62 on diet < 2 years 41 on diet 2 ± 5 years 43 on diet > 5 years 24 .Methods Calgary Clinic Children¶s 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 .

Calgary Clinic Pediatric Survey Data N= Median age of participants Age range participants % Female Median age at Dx Age range at Dx Member of CCA Calgary 146 11 yrs 1 ± 31 yrs 61% 8 yrs 1 ± 17 yrs 58% 25 .

thyroid (2) ‡ 14 / 21 ³asymptomatic´ reported improvement in 1 or more symptoms after starting GFD ± Fatigue ± 57%. nausea ± 36%. ³rarely / never´ ± 47% ‡ Many ³asymptomatic´ children retrospectively report symptoms that improve on a GFD and react to gluten 26 . Type-1-diabetes (4). ³somewhat´ ± 64%. ³sometimes´ ± 24%. bloating ± 36% ‡ Health improved: ³a lot´ ± 22%.Are Asymptomatic Children Really Asymptomatic? ‡ 125 symptomatic and 21 asymptomatic ± Family hx (15). abdo pain ± 43%. ³not at all/ worse´ ± 14% ‡ React to gluten: ³always´ ± 29%.

No ± 62% ‡ Family members diagnosed with celiac disease ± Yes. Some ± 41%. after my Dx ± 17% ± No ± 58% 27 . None ± 22% ‡ Second degree relatives screened ± Yes ± 38%.Follow up of family members after diagnosis ± Calgary study ‡ First degree relatives screened ± All ± 37%. before my Dx ± 25% ± Yes.

Follow up of family members after diagnosis ± Calgary study ‡ Family members starting GFD without biopsy ± Yes ± 17%. Never ± 5% ‡ My family reads labels to determine GF foods ± All/Most of time ± 94%. monthly ± 8%. No ± 81% ‡ My family eats gluten and I eat GFD ± All/Most of time ± 57%. weekly ± 15%. never ± 15% 28 . daily ± 34%. Some of time ± 37%. Never ± 2% ‡ I participate in determining if my food is GF ± Always ± 38%. Some of time ± 3%.

Anne Cranney. Graham. Marion Zarkadas. Connie Switzer.Canadian Pediatric Celiac Health Survey Mohsin Rashid. Vern Burrows.116:e754-759 29 . Ian D. Mavis Molloy. J Decker Butzner Pediatrics Dec 2005. Ralph Warren. Shelly Case.

Methods Canadian Survey Data on presentation of celiac disease ‡ Questionnaire sent to all members of the Canadian Celiac Association (n=5.048 respondents (65%) ‡ 194 children (<16 years) ‡ 168 children had biopsy-confirmed celiac disease 30 .240) in 2002 ‡ 3.

Comparison of Calgary Clinic & Canadian Pediatric Survey Data N= Median age of participants Age range participants % Female Median age at Dx Age range at Dx Member of CCA Calgary 146 11 yrs 1 ± 31 yrs 61% 8 yrs 1 ± 17 yrs 58% Canada 168 9 yrs 2 ± 15 yrs 58% 3 yrs 1 ± 15 yrs 100% by def. 31 .

Comparison of Calgary Clinic & Canadian Pediatric Survey Data Reaction after accidental ingestion of gluten Calgary % with reaction Abdominal pain Diarrhea Bloating Fatigue Headache Median time to Sx Time range to Sx 61% 87% 67% 71% 51% 29% 2hrs Canada 54% 87% 64% 57% 37% 24% 2 hrs 15 min ± 48 hr 20 min ± 60 hr Most displayed more than one symptom during a reaction 32 .

Canada data (n = 168) All or Most of the time (%) (%) ‡ Avoided restaurants ‡ Avoided traveling 39 54 3 15 Some of the time (%) (%) 41 23 63 63 25 41 31 62 65 35 Never (%) (%) 20 5 75 54 24 10 34 8 ‡ Found it difficult to find 12 28 gluten-free foods at stores ‡ Found it difficult to determine if 3 27 the food was gluten-free ‡ Felt that they were not invited out 3 10 for meals due to celiac disease 72 53 33 .Celiac Health Surveys: Calgary & Canada Calgary data (n = 146).

Celiac Health Surveys: Calgary & Canada Calgary data (n = 146). Canada data (n = 168) All or Most of the time (%) (%) ‡ Felt left out of activities at school or friends¶ homes ‡ Felt different from other kids because of celiac disease ‡ Felt embarrassed to bring gluten-free foods to parties 8 13 20 18 9 23 Some of the time (%) (%) 38 48 34 41 21 48 51 30 49 22 Never (%) (%) 54 30 56 41 74 34 37 29 45 26 71 ‡ Felt angry about having to follow 15 23 a special diet ‡ Felt they can be healthy without following a special diet 4 4 .

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 Intentional 20% 64% 50% 13% 23% 13% 3% 4% 2% 4% 2% 2% Reasons No reaction to gluten ± 10%. No GF prep in home ± 3% 35 . Angry about CD ± 11%. No effect on health ± 8% Difficult to determine if Gluten Free ± 26%. Do not like taste of GF ± 10% Feel different ± 14%. Hidden gluten ± 41% Difficult to order GF meal ± 32%.

Gluten ingestion: Risk factors in Calgary Clinic ‡ Children with poor compliance displayed: ± Increasing age ± 40% >18yo. 21% 9-12yo. 29% 13-17 yo. 15% 2-5 yrs. 7% 5-8yo ‡ No effect on compliance: ± ± ± ± Age at diagnosis Sex of child Asymptomatic at diagnosis Membership in Canadian Celiac Assoc ± Time since diagnosis ± 40% >5yrs. 13% <2yrs 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% 36 .

10 to 20% continue to have significant difficulties in modifying their lifestyles ‡ Many ³asymptomatic´ children retrospectively report symptoms that improve on a GFD and react to gluten 37 .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.

McGowan Calgary Celiac Assoc Karen Renaud 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.Acknowledgements Summer students Derek Castiglione Kelly E. 38 .

Canadian Celiac Health Survey: Pediatric data (n=168) Other diagnoses prior to the diagnosis of celiac disease Anemia Irritable bowel syndrome Gastroesophageal reflux Stress Stomach ulcer % 15 11 8 8 4 39 .

Canadian Celiac Health Survey: Pediatric data (n=168) 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 .

Canadian Celiac Health Survey: Pediatric data (n=168) Clinical symptoms prior to diagnosis of celiac disease % Abdominal pain 90 Weight loss 71 Poor growth 70 Diarrhea 65 Extreme weakness64 Nausea. vomiting 53 Anemia 40 % Mood swings/depression37 Constipation 30 Eczema 24 Bone/joint pain 21 Mouth ulcers 16 Muscle cramps 14 Easy bruising 11 41 .

0% # of cases 42 .0% 10.0% 0.0% 50.ACH Celiac Disease Database Number of Cases Diagnosed Number 200 180 160 140 120 100 80 60 40 20 0 1990-1995 1996-2000 Year 2001-2006 Per cent with Classic CD 70.0% 20.0% Percentage of years total # of cases 60.0% 40.0% 30.

Short Stature/Delayed Puberty ‡ Short stature in children / teens: y b10% of short children and teens have evidence of celiac disease Higher prevalence in teens with untreated celiac disease ‡ Delayed menarche: y 43 .

681 patients ‡ 37 % of patients saw 2 or more physicians prior to diagnosis ‡ Celiac disease has many atypical presentations 44 .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.

the disease could result in difficult to manage complications 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.

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