1. Diagnosis and Treatment of Celiac Disease in Children
Dr.Fawaz ALRefaee, MBBS FAAP FRCPC
Pediatric Gastroenterologist,Al-Adan Hospital
KMA Conferance
March 18,2016

2. Outline
-Case presentation -Definition -Epidemiology -Clinical features -Pathogenesis -Diagnosis -Treatment

3. Case presentation 14 month old F with FTT
Watery diarrhea x 2 months; 3-10 episodes per day; stool infectious work-up by PCP negative
No nausea, vomiting, abdominal pain, abdominal distention, hematochezia, melena
No improvement in symptoms with change to soy milk
No significant PMH or FH
PE: Pale skin, abdomen distended but soft and nontender, normal bowel sounds, no organomegaly

4. Growth Chart

5. Labs WBC 14.1, Hb 9.7, Plt 392; normal MCV and iron studies
AST 30, ALT 23, albumin 28
Hemoccult negative, stool WBC negative, spot fecal fat test positive
Celiac Panel
IgA level was normal
Endomysial AB Positive
Tissue Transglutaminase IgA AB >100*
Negative = < 15

6. What is Celiac Disease? Auto-immune condition
Occurs in genetically susceptible individuals
A unique autoimmune disorder because…
Environmental trigger (gluten) and the autoantigen (tissue-transglutaminase) are known
Elimination of the environmental trigger leads to a complete resolution of the disease
Permanent sensitivity to gluten

7. Why is it Important?
If untreated it poses long-term adverse health consequences including:
Malabsorption
Anemia
Poor growth
Osteopenia
Intestinal lymphoma
Nutritional Deficiencies
Iron, zinc, calcium, Vitamin A, D, E, and K

8. Relatives 1:133 1st degree relatives: 1:18 to 1:22
• Healthy population:
1:133 •
1st degree relatives:
1:18 to 1:22 •
2nd degree relatives:
1:24 to 1:39
Fasano, et al, Arch of Intern Med, Volume 163: , 2003 25

9. Prevalence of Celiac Disease is Higher in Other Autoimmune Conditions
Type 1 Diabetes Mellitus: Thyroiditis: %
4 - 8%
Arthritis: %
Autoimmune liver diseases: Sjögren’s syndrome:
6 - 8%
2 - 15%
Idiopathic dilated cardiomyopathy: IgA nephropathy:
5.7%
3.6% 24

10. Genetic Disorders • Down Syndrome: 4-19% • Turner Syndrome: 4-8%
• Williams Syndrome: 8.2%
• IgA Deficiency: 2-3%
• Can complicate serologic screening 23

11. The Celiac Iceberg Symptomatic Celiac Disease Manifest mucosal lesion
Silent Celiac
Disease
Latent Celiac Disease
Normal
mucosa
Genetic susceptibility: - DQ2, DQ8
Positive serology

12. Risk Factors for Celiac Disease
The Grains
The Genes

13. Pathogenesis

14. Genetics Strong HLA association
90-95% of patients HLA DQ2 –also found in 20-30% of controls
Concordance in MZ twins is 70%
HLA-DQ2 and /or DQ8 genes are necessary (No DQ2/8,no celiac disease!) but not sufficient for the development of the disease

15. Clinical Manifestations
Gastrointestinal Symptoms (“Classic”)
Chronic or recurrent diarrhea
Abdominal distention
Abdominal pain
Vomiting
Anorexia
Failure to thrive or weight loss
Constipation
Irritability
-- 25% of patients present with “classic” symptoms

16. “Classic” Celiac Disease

17. Asymptomatic Silent Latent
Silent: No or minimal symptoms, “damaged” mucosa and
positive serology
Identified by screening asymptomatic individuals
from groups at risk such:
First degree relatives
Down syndrome patients
Type 1 diabetes patients, etc.

18. Asymptomatic Silent Latent
Latent: No symptoms, normal mucosa
May show positive serology. Identified by following in time asymptomatic individuals previously identified at screening from groups at risk. These individuals, given the “right” circumstances, will develop at some point in time mucosal changes (± symptoms)

19. Abnormal Laboratory Findings in CD

20. Dermatitis Herpetiformis
Erythromatous papule> urticarial papule> tense vesicles
Symmetrical with severe pruritis
90% no GI symptoms
Gluten sensitive
75% villous atrophy

21. Recurrent Aphtous Stomatitis
By permission of C. Mulder, Amsterdam (Netherlands) 33

22. Short Stature/Delayed Puberty
Short stature in children/teens:
About 10% of short children and teens have evidence of celiac disease
Delayed menarche
Higher prevalence in teens with untreated celiac disease

23. Dental Enamel Defect Involve the secondary dentition
Could be the only presenting sign of celiac disease

24. Osteoporosis

25. Celiac Disease Complicated by Enteropathy-Associated T-cell Lymphoma (EATL)
By permission of G. Holmes, Derby (UK)

26. Neurological and Behavioral Problems
Zelnick et al. Pediatrics

28. Serological Tests Role of serological tests:
Identify symptomatic individuals who need a biopsy
Screening of asymptomatic “at risk” individuals
Supportive evidence for the diagnosis
Monitoring dietary compliance
-- Recommendation to screen all first-degree relatives of patients with CD with serologic testing

29. Tissue Transglutaminase - TTG
IgA based antibody against tissue transglutaminase (Celiac Disease autoantigen)
Advantages
high sensitivity and specificity (human TTG)
non operator dependent (ELISA/RIA)
relatively cheap
Disadvantages
false negative in young children
false negative in IgA deficiency
possibly less specific than EMA
The tissue transglutaminase test is IgA based and performed by means of either an ELISA or RIA technique. The major advantages of the test are that it is highly sensitive and specific, is non operator dependent and is relatively cheap to perform. The disadvantages are that it is unable to detect celiac disease in IgA deficient individuals and it may be less specific than the endomysial antibody.

30. Endomysial Antibody - EMA
NEGATIVE
POSITIVE
Antibodies against the outer layer of the smooth muscle of monkey esophagus
This slide illustrates the microscopic appearance of a positive of endomysial antibody test.

31. Serum IgA Level
Individuals with IgA deficiency are at increased risk for Celiac Disease
IgA deficient individuals will have negative EMA-IgA & TTG-IgA
Check IgA levels with Celiac Disease serology in all symptomatic individuals
Consider IgG based tests (EMA-IgG & TTG-IgG) in IgA deficiency
It is known that individuals with selective IgA deficiency are at increased risk for celiac disease. This presents a problem when using serological tests for screening purposes as most tests are based upon an IgA antibody and hence will give a negative result. In order to better interpret the relevance of a negative endomysial or transglutaminase test in a symptomatic individual, determination of a serum IgA level is helpful. In the event the individual has a low serum IgA level indicative of IgA deficiency, the IgA based endomysial and transglutaminase tests will fail to identify those who have celiac disease. In such cases additional strategies are needed. One such strategy is to use IgG based anti-endomysial and anti-tissue transglutaminase tests that are offered by some commercial laboratories. Studies suggest these are not as sensitive or specific as the IgA based tests but are superior to the IgG based anti-gliadin tests. If the clinical suspicion for celiac disease is strong, it may be necessary to proceed to an intestinal biopsy even if all serological tests for celiac disease are negative.

32. Serological Test Comparison

33. Endoscopic Findings

34. Intestinal Histopathology
Histologic abnormalities associated with CD are characteristic, but not completely specific.
Classically, small intestinal mucosal surface is flattened with absence or marked blunting of intestinal villi
Total absorptive surface area is greatly reduced
There are typically an increased number of inflammatory cells present in the lamina propria (plasma cells, CD4 cells)

35. HLA Tests Potential role for DQ2/DQ8 Asymptomatic relatives
Trisomy 21, Turner & Williams syndrome
Type 1 diabetes
Diagnostic dilemmas
TTG +, EMA -, Bx -, Symptoms +

36. Treatment
Only treatment for Celiac Disease is a gluten-free diet (GFD)
Strict, lifelong diet
Avoid:
Wheat
Rye
Barley
Oats?
-- Follow serology to confirm adherence to gluten-free diet. If serology does not normalize, continued exposure is likely. Involvement of an experienced dietician is critical – often able to identify hidden exposures.

37. Why is Adherence Important?
Good evidence to suggest that when children with symptomatic celiac disease adhere to a GFD it results in resolution of GI symptoms, improved growth in height and weight, and normalization of hematological and biochemical parameters.
Celiac disease is associated with an overall increased risk of mortality in adults which is primarily the result of GI malignancies. When CD is diagnosed in childhood and GFD is initiated, there appears to be no increased cancer risk and reduced risk of other autoimmune diseases.

38. Diagnostic Approach in symptomatic child

39. Summary
Celiac Disease is a common, subtle enteropathy with variable presentation.
Active, appropriate screening is needed to avoid long-term complications of untreated CD.
Life long adherence to the diet is important

40. Thanks Questions!