Prof. Dr. Giuseppe Magazzu Prof. Dr. Dušanka Mičetić-Turk and all Progress of the Prospective...
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Transcript of Prof. Dr. Giuseppe Magazzu Prof. Dr. Dušanka Mičetić-Turk and all Progress of the Prospective...
Prof. Dr. Giuseppe Magazzu
Prof. Dr. Dušanka Mičetić-Turk
and all
Progress of the Prospective study - Medicel
Background
Celiac disease (CD)has increased at an unexpected rate in the last two decades not only in Europe but also in Mediterranean regions.
The consequences of unrecognized CD can be severe particularly with regard to mortality and morbidity among these patients.
The aims of study:
To identify the factors that may influence the onset of CD in Mediterranean basin
To identify clinical and laboratory data which can predict the diagnosis of the disease
To determine where the new ESPGHAN diagnostic criteria could be applied and what % of patients can omitt the biopsy
Service and survey design: Prospective cohort observational survey
Duration: April 2013 to March 2014
Setting: 13 CD centers from 12 Mediterranean countries:Albania, Algeria, Croatia, Egypt, Greece, Italy,Malta, Montenegro, Morocco, Slovenia, Tunisia, Turkey
Sample: unselected new cases referred for suspected CD
Patients
Data of patients were collected and put into a web-based database of Medicel Mediterranean Network (www.medicel.unina.it/)
Which data were collected?
• Pregnancy duration and outcome• Birth weight• Breastfeeding• Age of gluten introduction into the diet• Number of previous admissions to hospital• Clinical symptoms (main, second and third)• Familiarity• Associated diseases
Which data were collected?
• Antitransglutaminase antibodies IgA (t-TG) as Nx upper limit of normal (ULN)
• Endomysial antibodies (EMA)• HLA-DQ2/DQ8• Histology (Marsh-Oberhuber classification)• DNA, sera and tissue frozen samples were
collected for further studies• Follow-up to confirm uncertain case
Statistics
Crosstabs and stepwise statistics were generated by SPSS and t-Test, Odds Ratio (OR) and Positive Predictive Value (PPV) were estimated for variables.
Results of the study
Country Total CD NCD
Albania 31 28 3
Algeria 31 21 10
Croatia 9 8 1
Egypt 20 15 5
Greece 35 29 6
Italy-Me 270 100 170
Italy-Na 339 196 143
Malta 10 9 1
Monten. 8 8 0
Morocco 85 49 36
Slovenia 61 31 30
Tunisia 41 20 21
Turkey 104 23 81
PATIENTS ENROLLED INTO THE STUDY
Results
1044 patients enrolled 537 CD
In 460 gold standard intestinal biopsy In 77 gold standard EMA positive
507 NCD 491 NCD 16 potential CD (15 EMA positive)
Results
Duration of gestation and breastfeeding were significantly longer in CD
NCD had a heavier birth weight No difference was found for age of
gluten introduction and number of previous hospital admissions
ResultsSymptoms PPV (95% CI) OR (95% CI)
Anorexia/lack of appetite
73% (62-81) 2.74 (1.64-4.60)
Abdominal distention
68% (60-76) 2.30 (1.55-3.42)
Anemia 63% (53-71) 1.71 (1.11-2.63)
Vomit 54% (48-62) 1.50 (1.07-2.10)
Abdominal pain 63% (53-71) 0.66 (0.50-0.87)
Contipation 37% (30-44) 0.51 (0.35-0.74)
Familiarity and associated diseases
CD NCD
Famil. 117 83
No Famil 306 411
CD NCD
As. Dis. 104 80
No As. Dis
425 435
Familiarity OR 1.89(1.38-2.6) Ass. Diseases OR 1.33 (0.97-1.83)
Results PPV of tTGA > 10 x ULN: 0.951 (95% CI:0.922-
0.969); LR+ = 21.1 (95%CI: 13.0-34.37). Out of 537 CD, in 77 no biopsy
Out of 460 pts with M2-3, 308 (67%) had tTGA > 10 x ULN: 78 no EMA
230 (50%) EMA positive with M 2-3 might have avoided intestinal biopsy according to ESPGHAN NGL
4.6% with tTGA > 10 x ULN (EMA positive) had a potential CD.
Conclusion This large prospective study provides for the
first time PPV, that is the pre-test probability, of symptoms.
Based on tTGA diagnostic accuracy obtained in own laboratory, single centers can make clinical decision on if and when intestinal biopsy may be omitted, according to the new ESPGHAN guidelines.
There is a chance to meet potential CD even in the presence of a tTGA > 10 x ULN value.
Conclusion
The results of the study raises many questions, the most important:
• Is it ever justifiable to place a child with gastrointestinal symptoms on a gluten-free diet without clearly making a diagnosis of CD?
Pre-test probability of a symptom
e.g. anorexia
73%(62-81)
Decision threshold
PPV of tTGA > 10 x ULN: 0.951 (95% CI:0.922-0.969); LR+ = 21.1 (95%CI: 13.0-34.37).
Conclusion The results of the study raises many questions, the most
important:
• Do we know the natural history of potential CD?• We have to determine which factors most
influence the onset of CD in Mediterranean basin
• Are repeat screenings necessary in NCD group, because CD can present at any age, and if so, at what intervals?
Conclusion The results of the study raises many questions, the most
important:
• In further evaluation we have to clearly identify: - which symptoms can be used to identify
children for screening and diagnostics? - which laboratory data predict the diagnosis of
CD?
Is the PoCT the ideal test?
CD NCD Total
PoCT + 51 3 54
PoCT - 0 54 54
Total 51 57 108
Sens. 100% Spec. 94.7 (88.9-100) LR+ 19 (6.3-57)
Acknowledgment
Stefania Marvaso Giovanni Curro’ Stefano Costa Salvatore Pellegrino Roberto Conti Nibali