Celiac Disease-A not so Uncommon Disorder

1. Celiac Disease-A not so Uncommon Disorder Frank A. Hamilton, M.D., MPH National Institutes of Health National Institute of Diabetes, Digestive and Kidney Diseases August 19, 2005

2. Definition Celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. It occurs in symptomatic subjects with gastrointestinal and non-gastrointestinal symptoms, and in some asymptomatic individuals, including subjects affected by: • - Type 1 diabetes - Williams syndrome • - Down syndrome - Selective IgA deficiency • Turner syndrome - First degree relatives of • individuals with celiac disease

3. Clinical Manifestations • Gastrointestinal (“classical”) • Non-gastrointestinal ( “atypical”) • Asymptomatic • In addition, Celiac Disease may be associated with other • conditions, and mostly with: • Autoimmune disorders • Some syndromes

4. The Celiac Iceberg Symptomatic Celiac Disease Manifest mucosal lesion Silent Celiac Disease Normal Mucosa Latent Celiac Disease Genetic susceptibility: - DQ2, DQ8 Positive serology

5. Gastrointestinal Manifestations(“Classic”) Most common age of presentation: 6-24 months • Chronic or recurrent diarrhea • Abdominal distension • Anorexia • Failure to thrive or weight loss Rarely: Celiac crisis • Abdominal pain • Vomiting • Constipation • Irritability

6. Typical Celiac Disease

7. Non Gastrointestinal Manifestations Most common age of presentation: older child to adult • Dermatitis Herpetiformis • Dental enamel hypoplasia of permanent teeth • Osteopenia/Osteoporosis • Short Stature • Delayed Puberty • Iron-deficient anemia • resistant to oral Fe • Hepatitis • Arthritis • Epilepsy with occipital • calcifications Listed in descending order of strength of evidence

8. Dermatitis herpetiformis

9. 3 – Asymptomatic Silent Latent • Silent: No or minimal symptoms, “damaged” mucosa and positive serology Identified by screening asymptomatic individuals from groups at risk such: • First degree relatives • Down syndrome patients • Type 1 diabetes patients, etc.

10. 3 – Asymptomatic SilentLatent • Latent: No symptoms, normal mucosa • May show positive serology. Identified by following in time asymptomatic individuals previously identified at screening from groups at risk. These individuals, given the “right” circumstances, will develop at some point in time mucosal changes (± symptoms)

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

12. Relatives • Healthy population: 1:133 • 1st degree relatives: 1:18 to 1:22 • 2nd degree relatives: 1:24 to 1:39 Fasano, et al, Arch of Intern Med, Volume 163: 286-292, 2003

13. Short stature Dermatitis herpetiformis Dental enamel hypoplasia Recurrent stomatitis Fertility problems Osteoporosis Gluten ataxia and other neurological disturbances Refractory celiac disease and related disorders Intestinal lymphoma Major Complications of Celiac Disease

14. Epidemiology The “old” Celiac Disease Epidemiology: • A rare disorder typical of infancy • Wide incidence fluctuates in space (1/400 Ireland to 1/10000 Denmark) and in time • A disease of essentially European origin

15. “Mines” of Celiac Disease Were Found Among: Patients with Relatives Associated diseases short stature, anaemia, fatigue, hypertransaminasemia “Healthy” groups autommune disorders, Down s, IgA deficiency, neuropathies, osteoporosis, infertility blood donors, students, general population

16. Prevalence 1:133 Celiac Disease Epidemiological Study in USA Population screened 13145 Healthy Individuals Risk Groups 4126 9019 2nd degree relatives Symptomatic subjects 1st degree relatives 1275 3236 4508 Positive Negative Positive Negative Positive Negative Positive Negative 1242 81 3155 205 4303 33 31 4095 Prevalence Prevalence Prevalence 1:40 1:22 1:39 Projected number of celiacs in the U.S.A.: 2,115,954 Actual number of known celiacs in the U.S.A.: 40,000 For each known celiac there are 53 undiagnosed patients. A. Fasano et al., Arch Int Med 2003;163:286-292.

17. The Global Village of Celiac Disease • In many areas of the world Celiac Disease is one of the commonest, lifelong disorders affecting around 1% of the general population. • Most cases escape diagnosis and are exposed to the risk of complications. • Active Celiac Disease case-finding is needed but mass screening should be considered. • The impact of Celiac Disease in the developing world needs further evaluation.

18. Diagnosis Diagnostic principles • Confirm diagnosis before treating • Diagnosis of Celiac Disease mandates a strict gluten-free diet for life • following the diet is not easy • QOL implications • Failure to treat has potential long term adverse health consequences • increased morbidity and mortality

19. Serological Tests Role of serological tests: • Identify symptomatic individuals who need a biopsy • Screening of asymptomatic “at risk” individuals • Supportive evidence for the diagnosis • Monitoring dietary compliance

20. Serological Tests • Antigliadin antibodies (AGA)* • *Antiendomysial antibodies (EMA) • *Anti tissue transglutaminase antibodies (TTG) • first generation (guinea pig protein) • second generation (human recombinant) • HLA typing • *2004 Consensus Conf. Best tests

21. Treatment • Only treatment for celiac disease is a gluten-free diet (GFD) • Strict, lifelong diet • Avoid: • Wheat • Rye • Barley

22. Oats –are they Safe? • Studies from 1970’s suggested that oats were toxic in CD • Oats contain a protein-avenin • Avenin- similar to wheat gliadin • Both are prolamins –rich in glutamine and proline, both amino acids

23. OATS • Avenin- proportion of proline and glutmaine is very low in oats compared to gliadin in wheat • 2004, Random. Clin Trial in • children fed GFD vs. GFD with oats • Hogberg Gut May 1, 2004 53(5)649-654.

24. Findings • First large study to indicate that oats in GFD do not prevent normalization of the small bowel tissue or celiac markers. • Other evidence supporting the safety of oats; G. Kilmartin Gut, January 1, 2003 • In CD, oats are not toxic and immunogenic, Srinivasan BMJ 1996:1300-01

25. OBVIOUS SOURCES Bread Bagels Cakes Cereal Cookies Pasta / noodles Pastries / pies Rolls Sources of Gluten

26. Treatment – 6 Elements in RX • Consultation with a skilled dietitian Education about the disease • Lifelong adherence to a gluten-free diet • Identification and treatment of nutritional deficiencies • Access to an advocacy group • Continuous long-term follow-up by a multidisciplinary team

27. Barriers to Compliance • Ability to manage emotions – depression, anxiety • Ability to resist temptation – exercising restraint • Feelings of deprivation • Fear generated by inaccurate information

28. Factors that Improve Adherence Internal Adherence Factors Include: • Knowledge about the gluten-free diet • Understanding the risk factors and serious complications can occur to the patient • Ability to break down big changes into smaller steps • Ability to simplify or make behavior routine • Ability to reinforce positive changes internally • Positive coping skills • Ability to recognize and manage mental health issues • Trust in physicians and dietitians