The Sicilian Step Forward on Celiac Disease MEDICEL Meeting Palermo, 2014 April 26 th

Case finding vs screening in sequence to bridge the diagnostic gap of CD in Sicily Background: more than 2/3 of CD patients are not recognized yet with possible severe consequences in terms of morbidity, mortality ans costs Aims: Primary: to assess the yield of two strategies for diagnosing CD in Sicily SecondarySecondary: to assess the PPV of the PoCT to assess the compliance to GFD and quality of life between patients diagnosed by case finding or by screening

DESIGN AND SETTING: Design: two phase prospective study Settings: Family Pediatrician Office (FPO) Referral center for CD

PATIENTS AND METHODS Two phases study: 1st phase: prospective case finding during a 6-month period

SYMPTOMS TO LOOK FOR Gastrointestinal symptms in the first 2 years of life Chronic diarrhoe and Irritable bowel syndrome Dyspepsia Weight loss Iron deficiency anemia Short stature compared with genetic target IDDM Hashimoto Tyroiditis Other autommine or rheumatologic disorders Epilepsy treatment resistant or wih occipatl localization Ataxia and peripherale neuropathies Dermatitis herpetiformis, Vitiligo, Alopecia areata, Psoriasis Chronic Orticaria Sine causa hypertransaminasemia (AST/ALT > 2 uln x 3 months) Enemal dental changes Stomatitis (> 3 episods/year) I or II degree relatives with CD

PATIENTS AND METHODS Two phase study: 1 st phase: prospective case finding during a 6-month period and referred to Center All children visited during this period were recorded 2 nd phase: hypothesizing a CD prevalence at screening of 0,01 and of 0,005 at case finding, setting α error at 0.05 and β error at 0.90, sample size needed find significant difference between two strategies was Children recorded in the 1st phase negative at case finding were consecutively offered PoC test in the order they went to FPO until complete utilization of the kits assigned to FP Gold standard: Marsh 2-3 at histology or EMA

Population in charge Case finding for 6 months Suspected 790 (3.2%) Enrolled 678 Refusal 112 (14%) I tTG + 34 II tTG + 21 CD confirmed Ist. 2 no Ist DSG 1 lost F.U. 3 Marsh 0 1 Marsh 1 1 F.U. tTG 11 Not suspected Performed PoC 3559 Pos 111 No line 45 To Centre Ist o EMA + 17 N IgA 35 tTG-G pos. 3c tTG-A 42 EMA N- In F.U. Neg 89 Neg 3448 Pos 20 IgA Def. 9 Lost FU 1 FU 3 Refusal 2 tTG-A 122, EMA + Marsh 3c Offered PoC 3642 Refused 83 (2.3%)

By total By CF By SC Known Celiac 103 (1:303)(1:236) Celiac after CF 118 (1:265)(1:206) Celiac after SC 137(1:228)(1:177)(1:187) Yield of Case finding: 15 new CD out of 678 suspected (1:45) Yield of screening: 19 new CD out of 3559 screened (1:187) CF Yield/SC Yield = 4:1 Elisa tTG Cost/PoCT Cost 6:1 Additional costs for CF: those of the unrecognized CD Additional costs for SC: those of 1:42 false positive

Screening vs Case finding in parallel to bridge the diagnostic gap of CD in Sicily Background: more than 2/3 of CD patients are not recognized yet with possible severe consequences in terms of morbidity, mortality ans costs. PoCT would be the ideal test to use it provided that its NPV is accepptable Aims: Primary: to assess the yield of two strategies for diagnosing CD in Sicily when they are applied in parallel SecondarySecondary: to assess the NPV of the PoCT

DESIGN AND SETTING: Design: one phase prospective study Settings: Family Pediatrician (FP), General Practioner (GP) Office and Referral center for CD

PATIENTS AND METHODS 8000 consecutive subjects prospectively seen at FP (4000) and GP (4000) office with the only exclusion criteria being an already known diagnosis of CD or a previous serological test for CD in the last year. They are offered PoCT and then asked regarding the presence of one or more symptoms or signs of CD foreseen in a case- finding questionnaire

SYMPTOMS TO LOOK FOR Gastrointestinal symptms in the first 2 years of life Chronic diarrhoe and Irritable bowel syndrome Dyspepsia Weight loss Iron deficiency anemia Short stature compared with genetic target IDDM Hashimoto Tyroiditis Other autommine or rheumatologic disorders Epilepsy treatment resistant or wih occipatl localization Ataxia and peripherale neuropathies Dermatitis herpetiformis, Vitiligo, Alopecia areata, Psoriasis Chronic Orticaria Sine causa hypertransaminasemia (AST/ALT > 2 uln x 3 months) Enemal dental changes Stomatitis (> 3 episods/year) I or II degree relatives with CD

PATIENTS AND METHODS 8000 consecutive subjects prospectively seen at FP (4000) and GP (4000) office with the only exclusion criteria being an already known diagnosis of CD or a previous serological test for CD in the last year. They are offered PoCT and then asked regarding the presence of one or more symptoms or signs of CD foreseen in a case-finding questionnaire All cases with PoCT positive, doubt or no line and those positive at case finding questionnaire will be sent the referral Center

PoCT NegPos CF= Case finding. Patients of Group 3 who are referred to Center allow to calculate NPV of PoC