Celiac Disease in Children: The Calgary Clinic Data  Calgary Celiac Disease Conference  25 October 2008 J. Decker Butzner,...
Disclosures <ul><li>Member Professional Advisory Board – Canadian Celiac Association </li></ul><ul><li>Member Professional...
Objectives <ul><li>Provide an update on the genetics  and pathophysiology of celiac disease </li></ul><ul><li>Southern Alb...
Definition <ul><li>Celiac disease is an autoimmune condition </li></ul><ul><li>Occurs in genetically susceptible individua...
Risk Factors The Grains The Genes Celiac disease is not just a  disease of Caucasians
Dietary Factors Festucoideae Subfamily Tribe Zizaneae   Oryzeae   Hordeae   Aveneae   Festuceaea   Chlorideae wild rice   ...
<ul><li>Multiple genes involved </li></ul><ul><li>The most consistent genetic component  depends on the presence of HLA-DQ...
Pathogenesis Celiac disease Gluten Necessary Causes Gender Infant feeding Infections Others Risk Factors Pathogenesis ? Ge...
Normal small bowel Celiac disease Gluten Gluten-free diet
APC Submucosa TTG T Intestinal lumen
Intestinal Lumen Submucosa TTG T APC
Intestinal lumen Submucosa T B AGA, EMA,  TTG Cytokines (IL-15) Tk P APC
“ Classic” Celiac Disease
Gastrointestinal Manifestations (“Nonclassic”) <ul><li>Irritable bowel syndrome – C & D types </li></ul><ul><li>Chronic di...
Non Gastrointestinal  Manifestations <ul><li>Dermatitis Herpetiformis </li></ul><ul><li>Iron-deficiency anemia  </li></ul>...
Associated Conditions Relatives IDDM Thyroiditis Down syndrome 0 4 8 12 16 20 percentage General Population
ACH Celiac Disease Database <ul><li>Create a database to examine incidence, primary symptoms, mode of presentation, associ...
Children Diagnosed with Celiac Disease at Alberta Childrens’  Hospital _______Pre-screening_____ _________Screening_______...
Comparison of Pre – Screening Era to the Screening Era in Calgary Clinic Pre-screening  (1990-96) Screening  (2000-06) Pat...
Clinical Presentations 1990 - 2006 *  Symptoms or conditions **  No GI symptoms †  Blood in stool, reflux ‡  No weight los...
Distribution of Patients by Presentation and Gender after Introduction of Screening n =  30  n = 82  n = 87 n = 123  n = 8...
Conclusions:  Impact of screening on the Calgary Clinic <ul><li>Screening tripled the incidence and quadrupled the median ...
Childhood Celiac Health Surveys: Calgary Clinic &  Canada <ul><li>Follow up of individuals with celiac disease </li></ul><...
  Methods Calgary Clinic  Children’s Survey  <ul><li>Questionnaire sent to 267 children who were  diagnosed with celiac di...
Calgary Clinic Pediatric Survey Data Calgary N = 146 Median age of  participants 11 yrs Age range participants 1 – 31 yrs ...
Are Asymptomatic Children Really Asymptomatic? <ul><li>125 symptomatic and 21 asymptomatic </li></ul><ul><ul><li>Family hx...
Follow up of family members after diagnosis – Calgary study <ul><li>First degree relatives screened </li></ul><ul><ul><li>...
Follow up of family members after diagnosis – Calgary study <ul><li>Family members starting GFD without biopsy </li></ul><...
Canadian Pediatric Celiac Health Survey Mohsin Rashid, Anne Cranney, Marion Zarkadas, Connie Switzer, Ian D. Graham, Shell...
Methods Canadian Survey  Data on presentation of celiac disease   <ul><li>Questionnaire sent to all members of the Canadia...
Comparison of Calgary Clinic & Canadian Pediatric Survey Data Calgary Canada N = 146 168 Median age of  participants 11 yr...
Comparison of Calgary Clinic & Canadian Pediatric Survey Data Reaction after accidental ingestion of gluten Most displayed...
<ul><li>All or Most Some of Never    of the time the time       (%)   (%) (%)   (%) (%)   (%)   </li></ul><ul><li>Avoided ...
<ul><li>All or Most Some of Never    of the time the time       (%)   (%) (%)   (%) (%)   (%)   </li></ul><ul><li>Felt lef...
Gluten Ingestion in Children in Calgary Clinic Reasons No reaction to gluten –  10% ,  No effect on health –  8% Difficult...
Gluten ingestion: Risk factors in Calgary Clinic <ul><li>Children with poor compliance displayed:  </li></ul><ul><ul><li>I...
Celiac Health Surveys:  Pediatric Data <ul><li>Calgary and Canadian data generally similar </li></ul><ul><li>Children with...
Acknowledgements Summer students  Calgary Celiac Assoc Derek Castiglione   Karen Renaud Kelly E. McGowan   Secretaries Tan...
Other diagnoses prior to the diagnosis of celiac disease Canadian Celiac Health Survey: Pediatric data (n=168)   % Anemia ...
Physician consulted before the diagnosis of celiac disease confirmed Canadian Celiac Health Survey: Pediatric data (n=168)...
% Abdominal pain 90 Weight loss 71 Poor growth 70 Diarrhea 65 Extreme weakness 64 Nausea, vomiting 53 Anemia 40 % Mood swi...
ACH Celiac Disease Database
Short Stature/Delayed Puberty <ul><li>Short stature in children / teens: </li></ul><ul><ul><li>  10% of short childre...
Why talk about celiac disease? <ul><li>Celiac disease affects between 1 in 100 and 1 in 300 North Americans </li></ul><ul>...
WHO criteria for disease screening <ul><li>Disease causes serious health problems </li></ul><ul><li>Screening test should ...
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Celiac Disease and Research Updates

  1. 1. 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
  2. 2. Disclosures <ul><li>Member Professional Advisory Board – Canadian Celiac Association </li></ul><ul><li>Member Professional Advisory Board – Canadian Celiac Association –Calgary Chapter </li></ul><ul><li>Financial Disclosures - Nil </li></ul>
  3. 3. Objectives <ul><li>Provide an update on the genetics and pathophysiology of celiac disease </li></ul><ul><li>Southern Alberta data on celiac disease in children </li></ul><ul><ul><li>Diagnosis </li></ul></ul><ul><ul><li>Follow up </li></ul></ul><ul><li>Compare to Canadian Pediatric Celiac Survey from 2002 </li></ul>
  4. 4. Definition <ul><li>Celiac disease is an autoimmune condition </li></ul><ul><li>Occurs in genetically susceptible individuals </li></ul><ul><ul><li>DQ2 and/or DQ8 positive HLA haplotype is necessary but not sufficient </li></ul></ul><ul><li>A unique autoimmune disorder because: </li></ul><ul><ul><li>both the environmental trigger (gluten) and the autoantigen (tissue Transglutaminase) are known </li></ul></ul><ul><ul><li>elimination of the environmental trigger leads to a complete resolution of the disease </li></ul></ul>
  5. 5. Risk Factors The Grains The Genes Celiac disease is not just a disease of Caucasians
  6. 6. Dietary Factors Festucoideae Subfamily Tribe Zizaneae Oryzeae Hordeae Aveneae Festuceaea Chlorideae wild rice rice wheat oat finger millet teff (ragi) rye barley The Grass Family - (GRAMINEAE)
  7. 7. <ul><li>Multiple genes involved </li></ul><ul><li>The most consistent genetic component depends on the presence of HLA-DQ (DQ2 and / or DQ8) genes </li></ul><ul><li>DQ2 or DQ8 found in 99% of celiac patients </li></ul><ul><li>DQ2 or DQ8 found in 40% of the general population </li></ul><ul><li>HLA-DQ2 and / or DQ8 genes are necessary (No DQ2/8, no Celiac Disease!) but not sufficient for the development of the disease </li></ul><ul><li>Other genes (not yet identified) account for 60 % of the inherited component of the disease </li></ul>Genetics HLA ? ? ? ? Gluten Celiac Disease + Genes
  8. 8. Pathogenesis Celiac disease Gluten Necessary Causes Gender Infant feeding Infections Others Risk Factors Pathogenesis ? Genetics
  9. 9. Normal small bowel Celiac disease Gluten Gluten-free diet
  10. 10. APC Submucosa TTG T Intestinal lumen
  11. 11. Intestinal Lumen Submucosa TTG T APC
  12. 12. Intestinal lumen Submucosa T B AGA, EMA,  TTG Cytokines (IL-15) Tk P APC
  13. 13. “ Classic” Celiac Disease
  14. 14. Gastrointestinal Manifestations (“Nonclassic”) <ul><li>Irritable bowel syndrome – C & D types </li></ul><ul><li>Chronic diarrhea without weight loss </li></ul><ul><li>Abdominal pain </li></ul><ul><li>Vomiting </li></ul><ul><li>Constipation </li></ul>
  15. 15. Non Gastrointestinal Manifestations <ul><li>Dermatitis Herpetiformis </li></ul><ul><li>Iron-deficiency anemia </li></ul><ul><li>resistant to oral Fe </li></ul><ul><li>Dental enamel hypoplasia </li></ul><ul><li>of permanent teeth </li></ul><ul><li>Osteopenia/Osteoporosis </li></ul><ul><li>Short Stature </li></ul><ul><li>Delayed Puberty </li></ul><ul><li>Elevated transaminases </li></ul><ul><li>Arthritis </li></ul><ul><li>Neurological </li></ul><ul><ul><li>- Epilepsy with occipital </li></ul></ul><ul><li>calcifications </li></ul><ul><li>- Ataxia </li></ul><ul><li>- Peripheral neuropathy </li></ul><ul><li>Infertility </li></ul>Most common age of presentation: older child to adult
  16. 16. Associated Conditions Relatives IDDM Thyroiditis Down syndrome 0 4 8 12 16 20 percentage General Population
  17. 17. ACH Celiac Disease Database <ul><li>Create a database to examine incidence, primary symptoms, mode of presentation, associated diseases and family history in children diagnosed at ACH since 1990 </li></ul><ul><li>Compare the prescreening era (1990 – 1996) to the screening era (2000 – 2006) </li></ul><ul><li>Collect prospective data on adherence to a gluten-free diet, ongoing health issues, quality of life in children with long standing celiac disease </li></ul>
  18. 18. Children Diagnosed with Celiac Disease at Alberta Childrens’ Hospital _______Pre-screening_____ _________Screening________ 266 children 61% female Median age at Dx 8 yrs
  19. 19. 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 <0.001 Incidence (/100,000/yr) 2.0 7.3 p <0.03 Incidence classic celiac disease (/100,000/yr) 0.8 1.6 p =0.154
  20. 20. Clinical Presentations 1990 - 2006 * Symptoms or conditions ** No GI symptoms † Blood in stool, reflux ‡ No weight loss or FTT 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 ±Anemia 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)
  21. 21. Distribution of Patients by Presentation and Gender after Introduction of Screening n = 30 n = 82 n = 87 n = 123 n = 86 2000 - 2006
  22. 22. Conclusions: Impact of screening on the Calgary Clinic <ul><li>Screening tripled the incidence and quadrupled the median age at diagnosis of celiac disease in children </li></ul><ul><li>The classic celiac presentation remains common (67%) in younger children (<3 yr old), while “atypical” presentations are frequently observed in older children </li></ul><ul><li>12 new clinical presentations observed in 42% of children in the screening group </li></ul><ul><li>Gastrointestinal symptoms still predominate the clinical presentation, but they are increasingly diverse </li></ul><ul><li>Currently, one quarter of children are diagnosed due to family history or a celiac-associated condition </li></ul>
  23. 23. Childhood Celiac Health Surveys: Calgary Clinic & Canada <ul><li>Follow up of individuals with celiac disease </li></ul><ul><li>diagnosed in childhood </li></ul><ul><li>Calgary Clinic includes children from Southern Alberta and SE British Columbia Children </li></ul><ul><li>Canadian data includes follow up children who are members of the CCA across the country </li></ul><ul><li>Calgary data (n = 146); Canada data (n = 168) </li></ul>
  24. 24. Methods Calgary Clinic Children’s Survey <ul><li>Questionnaire sent to 267 children who were diagnosed with celiac disease from 1990 – 2006 </li></ul><ul><ul><li>45 were undeliverable </li></ul></ul><ul><li>146 /222 respondents ( 66% ) </li></ul><ul><li>Time since diagnosis 2.5 yr (range .5 – 17 years) </li></ul><ul><li> 62 on diet < 2 years </li></ul><ul><ul><li> 41 on diet 2 – 5 years </li></ul></ul><ul><ul><li> 43 on diet > 5 years </li></ul></ul>
  25. 25. Calgary Clinic Pediatric Survey Data Calgary N = 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%
  26. 26. Are Asymptomatic Children Really Asymptomatic? <ul><li>125 symptomatic and 21 asymptomatic </li></ul><ul><ul><li>Family hx (15), Type-1-diabetes (4), thyroid (2) </li></ul></ul><ul><li>14 / 21 “asymptomatic” reported improvement in 1 or more symptoms after starting GFD </li></ul><ul><ul><li>Fatigue – 57%, abdo pain – 43%, nausea – 36%, bloating – 36% </li></ul></ul><ul><li>Health improved: “a lot” – 22%, “somewhat” – 64%, </li></ul><ul><li>“ not at all/ worse” – 14% </li></ul><ul><li>React to gluten: “always” – 29%, “sometimes” – 24%, “rarely / never” – 47% </li></ul><ul><li>Many “asymptomatic” children retrospectively report symptoms that improve on a GFD and react to gluten </li></ul>
  27. 27. Follow up of family members after diagnosis – Calgary study <ul><li>First degree relatives screened </li></ul><ul><ul><li>All – 37%, Some – 41%, None – 22% </li></ul></ul><ul><li>Second degree relatives screened </li></ul><ul><ul><li>Yes – 38%, No – 62% </li></ul></ul><ul><li>Family members diagnosed with celiac disease </li></ul><ul><ul><li>Yes, before my Dx – 25% </li></ul></ul><ul><ul><li>Yes, after my Dx – 17% </li></ul></ul><ul><ul><li>No – 58% </li></ul></ul>
  28. 28. Follow up of family members after diagnosis – Calgary study <ul><li>Family members starting GFD without biopsy </li></ul><ul><ul><li>Yes – 17%, No – 81% </li></ul></ul><ul><li>My family eats gluten and I eat GFD </li></ul><ul><ul><li>All/Most of time – 57%, Some of time – 37%, Never – 5% </li></ul></ul><ul><li>My family reads labels to determine GF foods </li></ul><ul><ul><li>All/Most of time – 94%, Some of time – 3%, Never – 2% </li></ul></ul><ul><li>I participate in determining if my food is GF </li></ul><ul><ul><li>Always – 38%, daily – 34%, weekly – 15%, monthly – 8%, never – 15% </li></ul></ul>
  29. 29. 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
  30. 30. Methods Canadian Survey Data on presentation of celiac disease <ul><li>Questionnaire sent to all members of the Canadian Celiac Association (n=5,240) in 2002 </li></ul><ul><li>3,048 respondents (65%) </li></ul><ul><li>194 children (<16 years) </li></ul><ul><li>168 children had biopsy-confirmed celiac disease </li></ul>
  31. 31. Comparison of Calgary Clinic & Canadian Pediatric Survey Data Calgary 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 yrs Age range at Dx 1 – 17 yrs 1 – 15 yrs Member of CCA 58% 100% by def.
  32. 32. Comparison of Calgary Clinic & Canadian Pediatric Survey Data Reaction after accidental ingestion of gluten Most displayed more than one symptom during a reaction 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
  33. 33. <ul><li>All or Most Some of Never of the time the time (%) (%) (%) (%) (%) (%) </li></ul><ul><li>Avoided restaurants 39 54 41 41 20 5 </li></ul><ul><li>Avoided traveling 3 15 23 31 75 54 </li></ul><ul><li>Found it difficult to find 12 28 63 62 24 10 </li></ul><ul><li>gluten-free foods at stores </li></ul><ul><li>Found it difficult to determine if 3 27 63 65 34 8 </li></ul><ul><li>the food was gluten-free </li></ul><ul><li>Felt that they were not invited out 3 10 25 35 72 53 </li></ul><ul><li>for meals due to celiac disease </li></ul>Celiac Health Surveys: Calgary & Canada Calgary data (n = 146); Canada data (n = 168)
  34. 34. <ul><li>All or Most Some of Never of the time the time (%) (%) (%) (%) (%) (%) </li></ul><ul><li>Felt left out of activities at 8 13 38 48 54 37 </li></ul><ul><li>school or friends’ homes </li></ul><ul><li>Felt different from other kids 20 18 48 51 30 29 </li></ul><ul><li>because of celiac disease </li></ul><ul><li>Felt embarrassed to bring 9 23 34 30 56 45 </li></ul><ul><li>gluten-free foods to parties </li></ul><ul><li>Felt angry about having to follow 15 23 41 49 41 26 </li></ul><ul><li>a special diet </li></ul><ul><li>Felt they can be healthy without 4 4 21 22 74 71 </li></ul><ul><li>following a special diet </li></ul>Celiac Health Surveys: Calgary & Canada Calgary data (n = 146); Canada data (n = 168)
  35. 35. 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% 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%
  36. 36. Gluten ingestion: Risk factors in Calgary Clinic <ul><li>Children with poor compliance displayed: </li></ul><ul><ul><li>Increasing age </li></ul></ul><ul><ul><ul><li>40% >18yo, 29% 13-17 yo, </li></ul></ul></ul><ul><ul><ul><li>21% 9-12yo, 7% 5-8yo </li></ul></ul></ul><ul><ul><li>Time since diagnosis </li></ul></ul><ul><ul><ul><li>40% >5yrs, 15% 2-5 yrs, 13% <2yrs since diagnosis </li></ul></ul></ul><ul><ul><li>Reaction to gluten </li></ul></ul><ul><ul><ul><li>23% no/rare reaction </li></ul></ul></ul><ul><ul><ul><li>33% sometimes reaction </li></ul></ul></ul><ul><ul><ul><li>12% always reaction </li></ul></ul></ul><ul><ul><li>No medical follow up for celiac disease – 38% </li></ul></ul><ul><ul><li>Medical follow up – 15% </li></ul></ul><ul><li>No effect on compliance: </li></ul><ul><ul><li>Age at diagnosis </li></ul></ul><ul><ul><li>Sex of child </li></ul></ul><ul><ul><li>Asymptomatic at diagnosis </li></ul></ul><ul><ul><li>Membership in Canadian Celiac Assoc </li></ul></ul>
  37. 37. Celiac Health Surveys: Pediatric Data <ul><li>Calgary and Canadian data generally similar </li></ul><ul><li>Children with celiac disease can present with a variety of symptoms </li></ul><ul><li>Many have had other diagnoses prior to that of celiac disease and delays in diagnosis are common </li></ul><ul><li>While most adjust well, 10 to 20% continue to have significant difficulties in modifying their lifestyles </li></ul><ul><li>Many “asymptomatic” children retrospectively report symptoms that improve on a GFD and react to gluten </li></ul>Conclusions
  38. 38. 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. 39. 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 8 Stress 8 Stomach ulcer 4
  40. 40. Physician consulted before the diagnosis of celiac disease confirmed Canadian Celiac Health Survey: Pediatric data (n=168) 24% consulted ≥ 2 family physicians 30% consulted ≥ 2 pediatricians 6% consulted ≥ 2 gastroenterologists Average time from development of symptoms to diagnosis = 1 year
  41. 41. % 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 Clinical symptoms prior to diagnosis of celiac disease Canadian Celiac Health Survey: Pediatric data (n=168)
  42. 42. ACH Celiac Disease Database
  43. 43. Short Stature/Delayed Puberty <ul><li>Short stature in children / teens: </li></ul><ul><ul><li>  10% of short children and teens have evidence of celiac disease </li></ul></ul><ul><li>Delayed menarche: </li></ul><ul><ul><li>  Higher prevalence in teens with untreated celiac disease </li></ul></ul>
  44. 44. Why talk about celiac disease? <ul><li>Celiac disease affects between 1 in 100 and 1 in 300 North Americans </li></ul><ul><li>Only 1 in 5 present with classic symptoms </li></ul><ul><li>It takes an average of 11 years from the onset of symptoms to make the diagnosis Canadian data – 2,681 patients </li></ul><ul><li>37 % of patients saw 2 or more physicians prior to diagnosis </li></ul><ul><li>Celiac disease has many atypical presentations </li></ul>
  45. 45. WHO criteria for disease screening <ul><li>Disease causes serious health problems </li></ul><ul><li>Screening test should be reliable (few false negatives and false positives) for the target disease </li></ul><ul><li>A treatment for the disease must be available </li></ul><ul><li>If not recognized in time, the disease could result in difficult to manage complications </li></ul>

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