1. Celiac disease is an immune-mediated disorder triggered by gluten in genetically susceptible individuals, characterized by clinical manifestations, anti-tissue transglutaminase antibodies, and enteropathy. 2. It has a prevalence of 1 in 300 to 1 in 80 children between ages 2.5-15 years. Increased risk is seen in those with type 1 diabetes, autoimmune liver/thyroid diseases, IgA deficiency, or having a first-degree relative with celiac disease. 3. Diagnosis involves testing for anti-tTG and EMA antibodies, followed by biopsy of the duodenum if antibodies are positive. A gluten-free diet is the primary treatment if celiac disease is confirmed

1. Diagnostic Criteria of celiac
disease
Dr. Virendra Kumar Gupta
MD Pediatrics,MIAP
Fellowship In pediatric Gastroentero-Hepatology & Liver Transplantation
Assistant Professor
Institute of Paediatric Gastroenterology
Nims University Jaipur

2. 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

3. CLINICAL SPECTRUM
• Symptomatic CD
– Frank clinical features
• Silent CD
– No symptoms but +ve serology and HPE.
– In most cases identified by serologic screening in at-risk groups
• Latent CD
– Normal HPE but before or after have shown Gluten dependent enteropathy
• Potential CD
– Normal HPE but Positive serology .
– It might or might not be symptomatic
ESPGHAN Guidelines for Diagnosis of Coeliac Disease

4. PREVALENCE IN CHILDREN BETWEEN
2.5 AND 15 YEARS OF AGE:
3 to 13 per 1000 children
or
approximately 1 in 300 to 1 in 80 children
CDHNF/NASPGHAN guidelines on the Diagnosis and Treatment of Celiac
Disease in Children JPGN ©2005; Volume 40, Number 1 (Jan): pages1-19.

5. Increased prevalence of CD in
children with
• Type 1 diabetes 2–12 %
• Autoimmune liver disease 12-13 %
• Autoimmune thyroid disease up to 7 %
• IgA deficiency 2-8 %
• Down’s syndrome 5-12 %
• Turner syndrome 2-5 %
• Williams’ syndrome up to 9 %
• First degree relatives with CD 10-20 %
Garampazzi A, Rapa A, Mura S, et al. Clinical pattern of celiac diseaseis
still changing. J Pediatr Gastroenterol Nutr 2007;45:611–4.

6. Prevalent, But Under Diagnosed
– Those not diagnosed have a higher death rate
– Raise awareness
IMPROVE
SCREENING

7. Celiac disease as a multiorgan autoimmune disease
General:
Puberty & growth
delay
Malignancies
Anemia
GI system:
Diarrhea, vomiting
Distension, pain
Malnutrition,
weight loss
Hepatitis,
cholangitis
Bone:
Osteoporosis,
fractures
Arthritis
Dental anomalies
Skin & mucosa:
Dermatitis
herpetiformis
Aphtous
stomatitis
Hair loss
Heart:
Carditis
CNS:
Ataxia, seizures
Depression
Reproductive
system:
Miscarriage
Infertility

8. EVIDENCE-BASED
GUIDELINES FOR CD DIAGNOSIS
• AHRQ (USA, 2004)
Adults and children
Rostom A, et al.. Celiac Disease. EvidenceReport/ Technology
AssessmentNo. 104. AHRQ Publication No. 04-E029-2, 2004
• NICE guidelines (UK, 2009)
Adults and children
For GP’s and general paediatricians
NICE Clinical Guidelines 86. Coeliac Disease: Recognition
and assessment of coeliac disease. UK, May 2009

9. Guidelines: AHRQ (USA, 2004)
Main issues
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
Conclusions
1. Sensitivity and specificity
of EMA and TG2 are 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. Evidence Report/Technology
Assessment No. 104.AHRQ Publication No. 04‐E029‐2, 2004

10. Who Should Be Tested for CD?
Group 1:
unexplained symptoms and signs
chronic or intermittent diarrhoea,
failure to thrive, weight loss,
stunted growth, delayed puberty,
amenorrhoea, iron-deficiency
anaemia, nausea or vomiting,
chronic abdominal pain, cramping
or distension, chronic
constipation, chronic fatigue,
recurrent aphthous stomatitis
(mouth ulcers), dermatitis
herpetiformis–like rash,
fracture With inadequate
traumas/osteopenia/osteoporosi
, and abnormal liver biochemistry.
Group 2:
Asymptomatic increased risk
for CD
Type 1 diabetes mellitus
(T1DM)
Autoimmune thyroid disease
Autoimmune liver disease
IgA deficiency
Down syndrome
Turner syndrome
Williams syndrome
First-degree relatives

11. DIAGNOSTIC TOOLS
• CD-specific Antibody Tests
• Histological Analysis of Duodenal Biopsies
• HLA Testing for HLA-DQ2 and HLA-DQ8

12. ANTIBODIES
• Anti-tTG /TG2 (tissue transglutaminase)
• Anti-EMA (Endomysial antibody)
• Anti- DGP ( deamidated Gliadin Peptides)
– IgA level should be done with EMA/tTG
• Anti- Gliadin/Anti- Reticulin

13. SENSITIVITY/SPECIFICITY
Test % Sensitivity % Specificity Age
tTG-IgA 90-100 94-100 Children
84-100 91-100 Combined
EMA-IgA 87-95 95-100 Adults
88-100 90-100 Children
91-98 99-100 Combined
DGP 91 98 Combined
Am J Gastroenterol. 2009 Jan;104(1):154-63.

14. False Positive tTG/ Serology
– Other autoimmune conditions
– Infections
– Tumors
– Tissue damage

15. FALSE NEGATIVE SEROLOGY (tTG)
• Children younger than 2 yr
• Restricted gluten consumption
• Severe symptoms
• On immunosuppressive medications
• Technical problems

16. HISTOPATHOLOGY
• Crypt Hyperplasia
• Crypt to villous ratio is increased
• Intra-Epithelial Lymphocytosis
• Abnormal surface epithelium
• Subtotal to total villous atrophy

17. ENDOSCOPY & BIOPSY
Biopsies should be taken preferably during
upper endoscopy
bulb (at least 1 biopsy)
second or third portion of duodenum (at least 4
biopsies)

19. 19
Normal small bowel Celiac disease
Gluten
Gluten-free diet

20. MARSH Staging

21. Causes of Flat Mucosa (Villous Atrophy)
• Celiac Disease
• Giardiasis
• HIV Enteropathy
• PEM
• CMPI
• Bacterial Overgrowth
• Primary immunodeficiency
• Tropical sprue
• Chemotherapy & irradiation
• Eosinophilic Gastroenteritis

22. • Multiple genes involved
• The most consistent genetic component
depends on the presence of HLA-DQ
(DQ2 and/or DQ8) genes
• One or both of these genes are found in 95%
of celiac patients
• Having one or more of these genes doesn’t
mean you will develop celiac, but if you have
the disease you likely have the gene.
HLA
?? ?
?
Gluten
Celiac Disease
+
Genes
Genetics
22

23. HLA TYPING
• HLA DQ2 and DQ8
– Strong negative predictive value
– Present in > 95 % patients of CD
– Present in > 30% normal population
– Weak positive predictive value

24. • Diagnosis without biopsy is still not recommended in
India & Developing countries
• Reliable HLA testing and EMA estimation is not widely
available
• Secondly tTG is being done by various labs with
different kits and their standardization is doubtful, so
>10 times criteria is also difficult to implement.

25. Anti‐TG2 & total IgA*
Anti‐TG2
positive
Anti‐TG2
negative
Paed. GI discusses with family the 2 diagnostic
pathways and consequences considering patient’s
history & anti‐TG2 titers
Consider further diagnostic testing if:
IgA deficient
Age: < 2 years
History: ‐ low gluten intake
‐ drug pretreatment
-severe symptoms
-associated diseasesPositive Anti‐TG2
> 10 x normal
EMA & HLA testing for DQ2/DQ8
Positive Anti‐TG2
<10 xnormal
OEGD & biopsies
Not
available
Not CD
EMA+v
HLA +v
EMA+v
HLA -v
EMA-v
HLA -v
EMA-v
HLA +v
Marsh 0‐1 Marsh 2 or 3
CD+
GFD
& F/u
Consider
false neg.
HLA test
Consider
biopsies
Consider
false pos.
Anti‐TG2
Unclear case
Consider:
false pos. serology
false neg. biopsy or
potential CD
Extended evaluation of
HLA/serology/biopsies
GFD
& F/u
CD+
Child / Adolescent with Symptoms suggestive of CD
*or specific IgG based tests

26. HLA DQ testing (+/‐Anti‐TG2)
Consider retesting in intervals or
if symptomatic
HLA positive for
DQ2 and/or DQ8
Anti‐TG2 & total IgA*
EMA
Not CD,
no risk
Positive Anti‐TG2
> 3x normal
Marsh 2 or 3
CD+
GFD
& F/u
Consider:
Transient / false pos.
anti‐TG2
F/u on normal diet with
further serological
testing
Consider:
age, false neg. results,
exclude IgA deficiency and
history
of low gluten intake or drugs
Asymptomatic Person at Genetic Risk for CD
Explain implication of positive test result(s) and get consent for testing
HLA negative for
DQ2 and/or DQ8
Anti‐TG2 negativePositive Anti‐TG2
< 3x normal
Not CD
EMA negativeEMA positive
OEGD & biopsies:
1 x bulbus & 4 x pars
descendens, proper
histological work up
Unclear case
F/u on normal diet
Consider: false pos.
serology, false neg.
biopsy or potential CD
Marsh 0-‐1
*or specific IgG based tests

27. CELIAC DISEASE
Gluten Free Diet
Nutritional Education
Dietician
Periodic assessment of
Symptoms, Diet & Serology
Serology
Abnormal
?
Reinforce
adherence
Symptoms
Present ?
Evaluate for other causes
of symptoms
Consider Re- Biopsy
FOLLOW UP
Yes No
Yes
No

28. GLUTEN CHALLENGE- When and How ?
• Performed under special circumstances- Doubt exists about the initial
• Gluten challenge should be discouraged
Before a child is 5 years old
During the pubertal growth spurt
• Gluten challenge always should be performed
Under strict medical supervision
Preferably by a paediatric gastroenterologist
Preceded by HLA testing /assessment of duodenal histology
Ensuring that a normal amount of gluten in the diet is ingested
IgA anti-tTg antibody should be measured during the challenge period
Challenge for practical purposes is considered-Complete after 2 years
Follow-up should be continued -relapse may occur at a later time.

29. Why different algorithms for symptomatic and
asymptomatic (at risk) patients?
1. False positive or transient TG2 antibody levels
more frequent in genetically at risk persons
than symptomatic cases
2. TG2 titres with normal histology (Marsh 0) are
often of low titre (<3 x upper limit of normal)
3. In asymptomatic patients with low antibody
levels there no urgency to perform biopsies
compared to symptomatic patients with the
same low levels.

30. Treatment
• GLUTEN FREE DIET (dietician consult)
• Identification and treatment of
nutritional deficiencies
• Pneumococcal vaccine

31. “A New Hope For CD
Sufferers?”
• New study, no conclusions yet
• Pills that break down gluten
• Immunotherapy: training the immune system
to tolerate gluten through injections
+ ?

32. CONCLUSION
• CD is common
• IgA tTG -good screening test for CD. ( exceptions
< 2 years)
• A gluten-free diet (GFD) should be introduced
only after the completion of the diagnostic
process, when a conclusive diagnosis has been
made( expensive and lifelong diet ).

33. THANKS