Download - Celiac disease
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Diagnostic Criteria of celiac disease
Dr. Virendra Kumar GuptaMD Pediatrics,MIAP
Fellowship In pediatric Gastroentero-Hepatology & Liver Transplantation
Assistant Professor Institute of Paediatric Gastroenterology
Nims University Jaipur
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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
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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 symptomaticESPGHAN Guidelines for Diagnosis of Coeliac Disease
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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.
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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.
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Prevalent, But Under Diagnosed
– Those not diagnosed have a higher death rate– Raise awareness
IMPROVE SCREENING
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Celiac disease as a multiorgan autoimmune diseaseGeneral:
Puberty & growth delay
MalignanciesAnemia
GI system:Diarrhea, vomiting
Distension, painMalnutrition, weight lossHepatitis,
cholangitis
Bone:Osteoporosis,
fracturesArthritis
Dental anomalies
Skin & mucosa:Dermatitis
herpetiformisAphtous
stomatitisHair loss
Heart:Carditis
CNS:Ataxia, seizures
Depression
Reproductive system:
MiscarriageInfertility
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EVIDENCE-BASEDGUIDELINES 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 childrenFor GP’s and general paediatricians
NICE Clinical Guidelines 86. Coeliac Disease: Recognition and assessment of coeliac disease. UK, May 2009
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Guidelines: AHRQ (USA, 2004)
Main issues1. Sensitivity/specificity of
serological tests2. Prevalence / incidence
of CD3. CD associated lymphoma4. Consequences of testing
for CD5. Interventions for
adherence to a gluten freediet
Conclusions1. Sensitivity and specificity
of EMA and TG2 are quitehigh
2. CD common, prevalencein the general populationlikely close to 1:100
3. Education/participation incoeliac societies improvescompliance with a GFD
Rostom A, et al.. Celiac Disease. Evidence Report/Technology Assessment No. 104.AHRQ Publication No. 04 E029 2, 2004‐ ‐
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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-deficiencyanaemia, nausea or vomiting,chronic abdominal pain, crampingor distension, chronicconstipation, chronic fatigue,recurrent aphthous stomatitis(mouth ulcers), dermatitisherpetiformis–like rash, fracture With inadequatetraumas/osteopenia/osteoporosi, and abnormal liver biochemistry.
Group 2:Asymptomatic increased risk
for CD Type 1 diabetes mellitus
(T1DM)Autoimmune thyroid diseaseAutoimmune liver diseaseIgA deficiencyDown syndromeTurner syndromeWilliams syndrome First-degree relatives
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DIAGNOSTIC TOOLS
• CD-specific Antibody Tests
• Histological Analysis of Duodenal Biopsies
• HLA Testing for HLA-DQ2 and HLA-DQ8
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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
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SENSITIVITY/SPECIFICITYTest % 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.
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False Positive tTG/ Serology– Other autoimmune conditions
– Infections
– Tumors
– Tissue damage
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FALSE NEGATIVE SEROLOGY (tTG)
• Children younger than 2 yr
• Restricted gluten consumption
• Severe symptoms
• On immunosuppressive medications
• Technical problems
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HISTOPATHOLOGY
• Crypt Hyperplasia
• Crypt to villous ratio is increased
• Intra-Epithelial Lymphocytosis
• Abnormal surface epithelium
• Subtotal to total villous atrophy
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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)
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19
Normal small bowel Celiac disease
Gluten
Gluten-free diet
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MARSH Staging
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Causes of Flat Mucosa (Villous Atrophy)
• Celiac Disease
• Giardiasis
• HIV Enteropathy
• PEM
• CMPI
• Bacterial Overgrowth
• Primary immunodeficiency
• Tropical sprue
• Chemotherapy & irradiation
• Eosinophilic Gastroenteritis
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• 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
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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
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• 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.
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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 deficientAge: < 2 yearsHistory: low gluten intake‐
‐ drug pretreatment-severe symptoms-associated diseases
Positive Anti‐TG2
> 10 x normal
EMA & HLA testing for DQ2/DQ8
Positive Anti‐TG2<10 xnormal
OEGD & biopsiesNot
available
Not CD
EMA+vHLA +v
EMA+vHLA -v
EMA-vHLA -v
EMA-vHLA +v
Marsh 0 1‐ Marsh 2 or 3
CD+
GFD& F/u
Consider false neg. HLA testConsider biopsies
Consider false pos. Anti TG2‐
Unclear caseConsider:
false pos. serologyfalse neg. biopsy or
potential CDExtended evaluation ofHLA/serology/biopsies
GFD& F/u
CD+
Child / Adolescent with Symptoms suggestive of CD
*or specific IgG based tests
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HLA DQ testing (+/ Anti TG2)‐ ‐
Consider retesting in intervals orif symptomatic
HLA positive forDQ2 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 CDExplain implication of positive test result(s) and get consent for testing
HLA negative forDQ2 and/or DQ8
Anti TG2 negative‐Positive Anti TG2‐< 3x normal
Not CD
EMA negativeEMA positive
OEGD & biopsies:1 x bulbus & 4 x parsdescendens, properhistological work up
Unclear caseF/u on normal dietConsider: false pos.serology, false neg.
biopsy or potential CD
Marsh 0- 1‐
*or specific IgG based tests
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CELIAC DISEASE
Gluten Free DietNutritional Education
Dietician
Periodic assessment of Symptoms, Diet & Serology
SerologyAbnormal
?
Reinforce adherence
Symptoms Present ?
Evaluate for other causes of symptoms
Consider Re- Biopsy
FOLLOW UP
Yes No
Yes
No
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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.
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Why different algorithms for symptomatic andasymptomatic (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.
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Treatment
• GLUTEN FREE DIET (dietician consult)
• Identification and treatment of nutritional deficiencies• Pneumococcal vaccine
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“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
+ ?
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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 ).
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THANKS