Impact of the new ESPGHAN diagnostic criteria for celiac disease in the Mediterranean area

The Mediterranean Network for Celiac DiseaseV Progress Meeting - Istanbul, June 30th 2012

Francesca Tucci

JPGN 2012;54: 136–160

CLINICAL CD GUIDELINESCLINICAL CD GUIDELINES

• To obtain a picture of the diagnostic facilities available in the 16 CD reference centers of the Mediterranean Basin

• To determine where the new ESPGHAN criteria could be applied and on what percentage of patients

• To estimates the likelihood of having a diagnosis of CD, both with and without endoscopy/histology results, to determine where the new criteria can be applied

AIM OF THIS CROSS SECTIONAL SURVEYAIM OF THIS CROSS SECTIONAL SURVEY

Country N of cases

Albania 43

Algeria 50

Bosnia Herzegovina 42

Croatia 50

Egypt 32

France 50

Greece 50

Italy (Campania) 50

Italy (Sicily) 50

Malta 32

Montenegro 50

Morocco 50

Slovenia 50

Spain 50

Tunisia 81

Turkey 50

Total 831

We analyzed 831 CD cases from the 16 CD reference We analyzed 831 CD cases from the 16 CD reference centers of the Mediterranean Basin centers of the Mediterranean Basin

Clinical, histological and laboratory data were Clinical, histological and laboratory data were collected through a standardized formcollected through a standardized form

Missing DataMissing DataCENTER SEROLOGY BIOPSY HLA

N.A. N.A. N.A.

Campania 0 (0%) 0 (0%) 89 (89%)

Sicily 1 (2%) 0 (0%) 34 (68%)

Turkey 2 (4%) 2 (4%) 16 (32%)

Greece 1 (2%) 0 (0%) 0 (0%)

Albania 0 (0%) 27 (62.8%) 43 (100%)

Croatia 3 (6%) 0 (0%) 48 (96%)

Slovenia 0 (0%) 0 (0%) 0 (0%)

Bosnia H 0 (0%) 8 (19%) 28 (66,7%)

Algeria 29 (58%) 0 (0%) 50 (100%)

Morocco 16 (32%) 0 (0%) 50 (100%)

France 4 (8%) 0 (0%) 46 (48%)

Tunisia 12 (14.8%) 2 (2.5%) 66 (81.5 %)

Egypt 0 (0%) 4 (12.5%) 32(100%)

Spain 0 (0%) 0 (0%) 0 (0%)

Montenegro 9 (18%) 2 (4%) 45 (90%)

Total 77 (9%) 45 (5.6%) 497 (66.4%)

A SIMPLE SCORING SYSTEM FOR THE DIAGNOSIS OF CDA SIMPLE SCORING SYSTEM FOR THE DIAGNOSIS OF CD

The aims of the scoring system are as follows:

•To positively diagnose coeliac disease at the initial assessment and be able to accept a diagnosis made in the past with biopsy•To simplify the diagnosis of CD in patients with obvious findings•To protect against overdiagnosis when only nonspecific findings are present•To compare by a standardized criteria the diagnostic capacities of each centre we computed the SAGE score for each case, by summing the clinical features to the serology and Histology data and adding the HLA data, when available

SAGE scoreSAGE score

• This cross-sectional study provides the first picture of the “pattern” of CD in these countries and of the diagnostic capabilities available in the reference centers evaluated

• Most cases were symptomatic and most showed the classical symptoms• tTGA assay is available in most of the countries evaluated, but it needs

standardization in more than one-third of countries• We applied the SAGE score to evaluate the diagnostic chances of an individual

having CD, almost all cases had a diagnostic score (> 4) when biopsy was available, but the vast majority of them (85%) would have diagnostic score without biopsy only if HLA testing were available

• Biopsy is generally available, but it is clear that many centers will require support in order to standardize the histological procedures. Biopsy is an obstacle to the dissemination

DiscussionDiscussion

WJGReviewer#1The authors seek to provides the first picture of the pattern of coeliac disease in the Mediterranean basin and to identify the diagnostic capabilities available in this area. They appear to have succeeded in this aim and I cannot make any suggestions or revisions to improve what is a very well written paperReviewer#2The data presented here has serious limitations. The data is quite heterogenous and retrospective in nature. 3 main parameters like tTGA assay biopsy and HLA have not been performed in all the patients. There is gross ununiformity of tTGA and biopsy reporting. The aim of the study has not been properly addressed

WJGReviewer#1The authors seek to provides the first picture of the pattern of coeliac disease in the Mediterranean basin and to identify the diagnostic capabilities available in this area. They appear to have succeeded in this aim and I cannot make any suggestions or revisions to improve what is a very well written paperReviewer#2The data presented here has serious limitations. The data is quite heterogenous and retrospective in nature. 3 main parameters like tTGA assay biopsy and HLA have not been performed in all the patients. There is gross ununiformity of tTGA and biopsy reporting. The aim of the study has not been properly addressed

JPGNReviewer #1The objective set for the study was "to obtain an objective picture of the facilities available for CD diagnosis in the reference centers of MEDICEL countries to determine where the new ESPGHAN diagnostic criteria could be applied and on what percentage of patients". This suggests a study that will contrast a certain number of tests to be done for diagnosis ("current" against "new" criteria), defined as "diagnostic criteria" and the facilities available, all of which will lead to calculate how many centers are able to adequately diagnose CD in the region assessed. Authors are not explicit about what they are comparing when they say "current criteria" (ESPGHAN 1990) and "new criteria". This latter refers to an important initiative of some researchers who have proposed a protocol i.e., a protocol to be tested but that by no means represents accepted new criteria. Rather this refers to exceptional cases in which a small intestinal biopsy can be not necessary. In statistical analysis authors declare "comparison between groups"; comparison should be between one set of criteria against the other and not between groups.

JPGNReviewer #1The objective set for the study was "to obtain an objective picture of the facilities available for CD diagnosis in the reference centers of MEDICEL countries to determine where the new ESPGHAN diagnostic criteria could be applied and on what percentage of patients". This suggests a study that will contrast a certain number of tests to be done for diagnosis ("current" against "new" criteria), defined as "diagnostic criteria" and the facilities available, all of which will lead to calculate how many centers are able to adequately diagnose CD in the region assessed. Authors are not explicit about what they are comparing when they say "current criteria" (ESPGHAN 1990) and "new criteria". This latter refers to an important initiative of some researchers who have proposed a protocol i.e., a protocol to be tested but that by no means represents accepted new criteria. Rather this refers to exceptional cases in which a small intestinal biopsy can be not necessary. In statistical analysis authors declare "comparison between groups"; comparison should be between one set of criteria against the other and not between groups.

Referee(s)' Comments to AuthorsReferee(s)' Comments to Authors

• To revise the data file in order to fill out our data• To have, for each country center, COMPLETE cases for the following:

Clinical informationAgeSexTgaseBiopsies

Need a change: Data fileNeed a change: Data file

• Type of test used: What tTG Kit each center use? Are the cut-off value standardized?

• Biological samples: Availability of storage sera

Need a change: Serology testsNeed a change: Serology tests

Criteria for assessment of biopsy:•Is Marsh Oberhuber criteria a standardized form?•Does each center use it?

Need a change: Biopsy criteriaNeed a change: Biopsy criteria

Marsh Type IEL / 100 enterocytes – jejunum

IEL / 100 enterocytes - duodenum

Crypt hyperplasia

Villi

0 <40 <30 Normal Normal

1 >40 >30 Normal Normal

2 >40 >30 Increased Normal

3a >40 >30 Increased Mild atrophy

3b >40 >30 Increased Marked atrophy

3c >40 >30 Increased Complete atrophy

For HLA we will consider the differences above the country resourcesBiological samples: Availability of DNAProposal: a DNA-bank to type all missing data (from saliva/blood)

HLAHLA

How can we improve this work?How can we improve this work?

• We have worked for more than a year • Deadline: end of July• Next journal: Digestive and Liver Disease