New ESPGHAN guidelines for the
diagnosis of Coeliac Disease in
Children and Adolescents
Steffen Husby
Hans Christian Andersen Children’s Hospital
Odense University Hospital, Denmark
Agenda
• Change in clinical paradigm
• Definitions of coeliac disease
• New diagnostic guidelines
• Algorithms
Interlaken ESPGHAN criteria (1979)
1. Small intestinal biopsy: villous atrophy
2. Gluten free diet for 1-2 years
3. Biopsy: normal.
4. Re-introduction of gluten
5. Biopsy: villous atrophy
McNeish et al. Arch Dis Childh 1979;54:783
Revised ESPGHAN criteria 1990
1. Small intestinal biopsy: villous atrophy
2. Clinical and serological improvement
after 2-3 months
• No further biopsy
• Provided age > 2 years
Walker‐Smithetal.ArchDisChild1990;65:99
General:
Puberty & growth delay
Malignancies
Anemia
GI system:
Diarrhea, vomiting

Towards a new definition of
coeliac disease
 Chronic
 Multi-organ
 Small intestinal inflammation
 Transglutaminase-related
ESPGHAN working group, 2011
Suggestion: New definition
 an immune-mediated systemic disorder
 elicited by gluten and related prolamines
 in genetically (mainly HLA) susceptible individuals
 characterized by a combination of:
• gluten dependent clinical manifestations
• anti-tissue transglutaminase (TG2) antibodies
• enteropathy
Husby et al. JPGN 2012
ESPGHAN classification

Silent CD:
positive CD antibodies and biopsy
findings, not sufficient symptoms to warrant
clinical suspicion of CD

Latent CD:
positive CD antibodies, no villous
atrophy. The patient has had a gluten-
dependent enteropathy. Patient may/may not
have symptoms

Potential CD:

Guidelines: AHRQ (USA, 2004)
1. Sensitivity/specificity of
serological tests
2. Prevalence / incidence
of CD
3. CD associated
lymphoma
4. Consequences of testing
for CD
5. Interventions for
adherence to a gluten-
free diet
1. Sensitivity and specificity
of EMA and TG2 ab quite
high
2. CD common, prevalence
in the general population
likely close to 1:100
3. Education/participation in
coeliac societies improves
compliance with a GFD
RostomA,etal CeliacDisease.EvidenceReport/TechnologyAssessmentNo.104.
AHRQPublicationNo.04‐E029‐2,2004
Main issues Conclusions
Evidence-based criteria for
clinical decisions
1. Formulate an answerable
question
2. Track down the best evidence
3. Critically appraise the evidence

excluded
n=334 Full text
Entering Level 2 screening
n=247
excluded
n=87
Entering Level 3 screening
n = 16 publications
Included in data synthesis
N = 71 excluded based on E1-8:
No biopsy
Age
Quality etc.
Giersiepen et al. 2010
Grading Evidence
Type of study: Diagnosis
Study Quality
Level 1: Good quality patient-oriented
evidence
 Validated clinical decision rule
 Systematic Review(SR)/meta-
analysis of high quality studies
 High quality diagnostic cohort study
Level 2: Limited quality patient-
oriented evidence
 Unvalidated clinical decision rule
 SR/meta-analysis of lower quality
studies or studies
 Lower quality diagnostic cohort study
or diagnostic case control study

• IgA and IgG Deamidated Gliadin Peptide (DPG)
antibody
• NOT: IgA and IgG anti-gliadin antibodies
DISEASE PREDICTION BY ANTIBODIES
(pooled estimates with 95% confidence values; § indicates high hetereog neity)
Positive
likelihood ratio
Negative
likelihood ratio
Odd’s
ratio
EMA /IgA
31.8
(18.6-54.3)
0.067
§
(0.038-0.118)
553
(218-1402)
Anti-TG2 /IgA
21.8
§
(12.9-36.8)
0.060
§
(0.040-0.090)
469
§
(250-880)
Anti-DGP /IgG

celiac: 0
10
3617
27
Mäki, N Engl J Med 2003
1:99
56
1.5%
9
Development of symptomatic coeliac
disease in EMA positive subjects
Predictive values for TG2 antibody
Positive predict. value
Toftedal et al. JCLM 2010
10
100
1000
10 20 30 40
Aesku 135 9.0
Binding Site 33.3 8.3
BMD Luminex 43
DiaSorin 57
Euroimmun 200 10.0
Eurospital* 95 13.6
Generic Assays 89 4.5
Genesis 69 9.9
Immco 48.3 2.4
Inova* 95.5 4.8
Orgentec 65.5 9.9
Phadia ELIA 69.0 9.9

HLA pos.
Not available
OEGD & biopsies
Anti-TG2
negative
EMA pos.
HLA neg.
EMA neg.
HLA neg.
EMA neg.
HLA pos.
Marsh 0-1 Marsh 2 or 3
Consider false
neg. HLA test.
Consider biopsies
Unclear case
Consider:
false pos. serology
false neg. biopsy or
p
otential CD
Consider false
pos. anti-TG2
CD+
CD+
EMA pos.
HLA pos.
EMA pos.
HLA neg.
EMA neg.

consequences considering patient’s history & anti-TG2 titers
Consider further diagnostic testing if:
IgA deficiency
Age: < 2 years
History: - low gluten intake
- drug pretreatment
- severe symptoms
- associated diseases
Anti-TG2 > 10 x normal
Anti-TG2 < 10 x normal
EMA & HLA DQ8/DQ2
Not available
OEGD & biopsies
Anti-TG2
negative