Celiac disease in Israel What we know Corina

Celiac disease in Israel What we know Corina Hartman, MD Schneider Children’s Medical Center MEDICEL meeting Cairo April 30 th- May 1 st

Epidemiology • DAHAN S, et al. Coeliac disease in the Rehovot-Ashdod region of Israel: incidence and ethnic distribution • Journal of Epidemiology and Community Health, 1984, 38, 58 -60 • Population of 250 000 • Mixed origin population: – 65% North African, Asian, or Middle Eastern – 35% Western in origin • Biopsies diagnosed celiac patients only

Epidemiology • DAHAN S, et al. Coeliac disease in the Rehovot-Ashdod region of Israel: incidence and ethnic distribution • Journal of Epidemiology and Community Health, 1984, 38, 58 -60

Epidemiology • The Use of a Single Serological Marker Underestimates the Prevalence of Celiac Disease in Israel: A Study of Blood Donors. SHAMIR R et al. • Am J Gastroenterol 2002; 97: 2589– 2594. • 1571 randomly serum samples • All samples were tested for: – Antigliadin antibodies (Ig. A and Ig. G), – hr. TTG antibodies, – EMA ELISA • EMA-IMF was performed in positive serum samples • Intestinal biopsy was offered to participants who tested positive for one of the following: TTG, EMA-ELISA, EMA-IMF

Epidemiology • The Use of a Single Serological Marker Underestimates the Prevalence of Celiac Disease in Israel: A Study of Blood Donors. SHAMIR R et al. • Am J Gastroenterol 2002; 97: 2589– 2594.

Epidemiology • The Use of a Single Serological Marker Underestimates the Prevalence of Celiac Disease in Israel: A Study of Blood Donors. SHAMIR R et al. • Am J Gastroenterol 2002; 97: 2589– 2594. • Prevalence 1: 157 is possible underestmation: – Biopsy performed in 30/ 59 of subjects with positive serology – Women represented only 22% in the sample cohort – Individuals with anemia or other complains may chose not to donate

Epidemiology • The Use of a Single Serological Marker Underestimates the Prevalence of Celiac Disease in Israel: A Study of Blood Donors. SHAMIR R et al. • Am J Gastroenterol 2002; 97: 2589– 2594. • EMA-IMF underestimated the prevalence of CD in Israel • TTG and EMA-ELISA kits had low sensitivity and positive predictive value. • CONCLUSION: • In a healthy population, the use of one serological marker is insufficient for establishing the true prevalence of CD.

Follow up after screening • Population screening for celiac disease: Follow up of patients identified by positive serology. SHAMIR R, et al • Journal of Gastroenterology and Hepatology 22 (2007) 532– 535 • Only 30/ 59 individuals identified with positive CD serology underwent duodenal biopsies, • GFD was followed only by 4/ 10 subjects diagnosed with CD • All subjects diagnosed with CD reported symptoms that should have rise the suspicion of CD

Follow up after screening • Population screening for celiac disease: Follow up of patients identified by positive serology. SHAMIR R, et al • Journal of Gastroenterology and Hepatology 22 (2007) 532– 535 • Sources for the low compliance with screening and FU: – – – Mild symptoms The attitude and the information received from the medical staff Patient’s own opinions and beliefs Confusing data from the mass media Absence of data on the natural history of asymptomatic CD GFD related obstacles: costs, palatability and social embarrassment – Negative effect of diagnosis/treatment on their quality of life

Serology testing • ELISA of anti-endomysial antibodies in the diagnosis of celiac disease: comparison with immunofluorescence assay of antiendomysial antibodies and tissue transglutaminase antibodies. • Shamir R, et al. Isr Med Assoc J. 2002 Aug; 4(8): 594 -6. • 21 subjects with positive EMA-IMF who underwent intestinal biopsy • TTG and EMA-ELISA • Antibody results were compared to the biopsy findings. A significant correlation was found between EMA-ELISA and TTG antibody titers (r = 0. 74, P < 0. 001

Serology testing • Comparison of assays for anti-endomysial and anti-transglutaminase antibodies for diagnosis of pediatric celiac disease. • Levine A, et al. Isr Med Assoc J. 2000 Feb; 2(2): 122 -5. • 33 patients with biopsyproven CD • 155 controls, normal biopsies • EMA ELISA and anti t. TTG antibodies Tissue transglutaminase-based ELISA test is both sensitive and specific for detection of celiac disease and can be used as a single first line test in children suspected of CD.

Cost effectiveness of mass screening for CD • Cost effectiveness of mass screenong for celiac disease is determined by time-delay to diagnosis and quality of life on a gluten free diet. HERSHCOVICI T, et al • Aliment pharmacol Ther 3010 Jan 19 (Epub ahead of print) • Cost-Effectiveness Analysis of Screening for Celiac Disease in the Adult Population, SHAMIR R et al. • Medical Decision Making 2006: 26(3); 282 -293 • Markov model of screening vs no screening: – Screening is CE if delay in diagnosis is > 6 years and utility of GFD adherence is greater than 0. 978 – Mass screening is CE assuming an SMR of 1. 5 or higher for untreated CD patients, in populations with a relatively high prevalence of CD over a wide range of ages at screening

Clinical Presentation • Follow Up of Children With Celiac Disease. Mozer-Glassberg Y, et al. • Retrospective electronic charts review (n=581, 1999 to 2008) • Data gathered: – Presenting signs and symptoms – Laboratory data – Duodenal biopsy histology – Adherence to GFD • Cohort characteristics: – Female 317 (59. 8%) – Mean age 7. 25 years (range 10 months-17. 9 years) • Diagnosis: – Clinical CD: 323 (60. 9%) • 6. 5 (10 m-18 y) – Asymptomatic CD: 64 (12. 1%) • 9. 9 (1. 8 -18 y) – Potential CD 55: (10. 4%) – No CD 88: (16. 6%)

Clinical presentation • Follow Up of Children With Celiac Disease. Mozer-Glassberg, et al. • Retrospective electronic chart review (CD, n=323, 1999 to 2008) Aphtous stomatitis 2% Constipation 3. 3% Weight loss 5. 8% Abdominal diistention 9. 5% Vomiting 3. 3% Foul stools 0. 8% Pubertal delay 0. 4% IDA 34% FTT 19. 5% Short stature 24. 5% Diarrhea 23. 7% Abdominal pain 24. 5%

Clinical Presentation Follow Up of Children With Celiac Disease. Mozer-Glassberg Y, et al. Retrospective electronic chart review (n=581, 1999 to 2008) Associated Autoimmune disorders • IDDM 47/ 63 (74. 6%) • Hypothyroidism 13/ 63 (12. 6%) • Crohn’s disease 2 (3. 2%) • Psoriasis 1 (1. 6%) 63/ 387 (16%)

Histology Follow Up of Children With Celiac Disease. Mozer-Glassberg Y, et al. Retrospective electronic chart review (n=581, 1999 to 2008) 551 duodenal biopsies were performed in 476 patients • Marsh 3: 353/ 387 (91. 2%) • Marsh 2: 9/ 387 (2. 3%) • Marsh 1: 13/ 387 (13%) • No biopsies were done in 12/ 387 (3. 1%)

Follow up Follow Up of Children With Celiac Disease. Mozer-Glassberg Y, et al. Retrospective electronic chart review (n=581, 1999 to 2008) Follow up after diagnosis of CD • 165/ 387 (47. 7%) were followed at SCMCI • 86/ 387 (22. 2%) were followed by their primary physician • 136/ 387 (35. 1%) no FU (half were asymptomatic) Compliance with GFD • 211/ 387 (54. 5%) follow GFD – 150/ 165 (91%) of children followed at SCMCI followed GFD – 60/ 86 (69%) of children followed by PP followed GFD

Conclusions • The prevalence of celiac disease in the healthy population of Israel is at lest 1/157 • In children the disease is diagnosed earlier in symptomatic patients • Majority of children diagnosed with CD have Marsh 3 lesions on duodenal biopsies • Children followed at a specialized center are more compliant with GFD • HLA typing is nor readily available or refundable in Israel

Conclusions • Mass screening will have to use 2 antibody tests • Mass screening for CD in the general population might be justified • There are, however, obstacles to overcome before mass screening will be recommended, especially natural history of asymptomatic CD individuals

WHAT A PLACE TO BE !!!