THE INS AND OUTS OF DIAGNOSIS & TREATMENT …...THE INS AND OUTS OF DIAGNOSIS & TREATMENT IN...
Transcript of THE INS AND OUTS OF DIAGNOSIS & TREATMENT …...THE INS AND OUTS OF DIAGNOSIS & TREATMENT IN...
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Dominica Gidrewicz, MD, FRCPCPediatric Gastroenterologist, Calgary, AB
Member of the Professional Advisory Committee, CCA
CELIAC DISEASE:
THE INS AND OUTS OF DIAGNOSIS & TREATMENT IN CHILDREN
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Diagnosis•Genetics•Serology•Biopsy & non-biopsy diagnosis•COVID-19 pandemic and postponement of elective
procedures
Management•Nutrition•Symptom resolution•Serology in follow-up •Monitoring for associated conditions
Outline
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•Strong hereditary component
•75% in monozygotic, 10% in dizygotic twins
•Best characterised genetic susceptibility
•HLA DQ2 and/or DQ8 (+) = 99.6% of CD patients
•30% of general population (+) for HLA DQ2
•Up to 80% of FDR are HLA DQ2/8 (+)
•Genetics necessary but not sufficient
•Other genes and/or environmental factors at play too
Kupfer S et Jabri B. Gastrointest Endoscopy Clin N Am 2012; 22: 639-660.
Genetics
Dominica Gidrewicz, MD
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Celiac Serology
Antibody Yr of discovery
Anti-gliadin (IgA and IgG AGA) 1983
Anti-endomysial (IgA EMA) 1983
Anti-tissue transglutaminase (IgA and IgG TTG)
1997
Anti-deamidated gliadin peptide (IgA and IgG DGP)
2001
Lerner A et al. Serologic Diagnosis of Celiac Disease: New Biomarkers Gastroenterol Clin N Am 2019; 307-317 Dominica Gidrewicz, MD
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Celiac Serology
Antibody Yr of discovery
Anti-gliadin (IgA and IgG AGA) 1983
Anti-endomysial (IgA EMA) 1983
Anti-tissue transglutaminase (IgA and IgG TTG)
1997
Anti-deamidated gliadin peptide (IgA and IgG DGP)
2001
Lerner A et al. Serologic Diagnosis of Celiac Disease: New Biomarkers Gastroenterol Clin N Am 2019; 307-317 Dominica Gidrewicz, MD
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•Must be eating gluten to do celiac screen
•Must be IgA sufficient
•Reflects intestinal damage and predicts degree of mucosal injury
•Reliable, inexpensive
•Total IgA and IgA-TTG
•Single best test for CD detection at any age
• If total IgA low:
• IgG based testing
• Inter-test & inter-laboratory variability
Celiac Serology – IgA TTG
Rubio-Tapia et al. ACG Clinical guidelines: Diagnosis and management of celiac disease. Am J Gastroenterol 2013; 108: 656-676.Husby et al. ESPGHAN guidelines for diagnosing celiac disease 2019 JPGN Dominica Gidrewicz, MD
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Variability in TTG test kits
Table A from ESPGHAN guidelines on diagnosis of celiac disease JPGN 2012; 54: 136 Dominica Gidrewicz, MD
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Causes of False Negative TTG
False Positive TTGs False Negative TTGs
1. Acute infection eg. Viral gastroenteritis
1. Diet low in gluten
2. Other autoimmune disorders :
Type 1 diabetes, SLE, IBD, Sjogren’s, PSC, autoimmune hepatitis
2. Patients < 2 yrs old
3. Lab error 3. Selective IgA deficiency
Dominica Gidrewicz, MD
TTG: Great test, but not perfect
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•Prospective study, 280 children
•Positive celiac serology but normal duodenal mucosa
•9 year follow-up period
•Villous atrophy = 15% (median 60 months)
• Seronegative for CD = 32%
Auricchio et al. Gastroenterol 2019; 157: 413-20.
Potential Celiac Disease
Dominica Gidrewicz, MD
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Upper endoscopy procedure
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Normal bowel Celiac disease
Duodenum - Endoscopy
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Duodenal Biopsy
0 1 2 3A 3B 3CModified Marsh
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•European Society for Pediatric GI, Hepatology & Nutrition (ESPGHAN)
•1st presented in 2012, revised in 2019:1. Symptoms and/or signs of celiac disease
2. IgA-TTG > 10 x ULN
Variability in performance of different TTG assays
3. Positive EMA – second blood sample
4. HLA DQ2 and/or DQ8 positive (no longer part of criteria)
•Option of omitting biopsies provided to family
•Response to GF diet and resolution of symptoms followed
ESPGHAN guidelines on diagnosis of celiac disease JPGN 2012; 54: 136.ESPGHAN guidelines for diagnosing celiac disease 2019 JPGN
Non-biopsy/serologic criteria
Dominica Gidrewicz, MD
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1. Nutrition & GFD
2. Symptom resolution
3. Serology in follow-up
4. Screening for associated conditions
Follow-up management
Dominica Gidrewicz, MD
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Nutritional aspects of the GF diet
Dominica Gidrewicz, MD
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Constipation common in kids on GFD
www.albertahealthservices.ca, Fiber and the GF diethttps://www.albertahealthservices.ca/assets/info/nutrition/if-nfs-fibre-and-the-gluten-free-diet.pdf
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Wessels et al Complementary serologic investigations in children with celiac disease is unnecessary during follow-up J Pediatrics 2016
Diagnosis Follow-up
Iron 28% 8%
IDA 9% 2%
Folate 14% 3%
Vitamin B12 1% 0%
Vitamin D 27% 25%
Nutritional Deficiency
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Wessels et al Complementary serologic investigations in children with celiac disease is unnecessary during follow-up J Pediatrics 2016
Diagnosis Follow-up
Iron 28% 8%
IDA 9% 2%
Folate 14% 3%
Vitamin B12 1% 0%
Vitamin D 27% 25%
Nutritional Deficiency
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Influencing factors in celiac disease
1. Intestinal malabsorption
2. Inflammation
3. Under-nutrition
4. Lifestyle variables
•Weight-bearing physical activity
•Sunlight exposure
BONE HEALTH –Ca & Vitamin D
Dominica Gidrewicz, MD
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•GFD quickly restores bones health
•Ca – 1000-1300 mg per day
•Vitamin D – 800-1000 IU per day
•Exercise to promote bone health
•BMD
•Not to be done routinely for all children
•Select patients with CD who do not adhere to GFD
BONE HEALTH - Management
Dominica Gidrewicz, MD
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Jericho H et al. JPGN 2017; 65: 75-79. Dominica Gidrewicz, MD
Extraintestinal features: Rate of improvement on a GFD
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• Is there accidental gluten exposure? •Most common reason
•Check celiac serology
Persistent Symptoms on a GFD
Dominica Gidrewicz, MD
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• Is there accidental gluten exposure? •Most common reason
•Check celiac serology
•Concurrent disorder? •Lactose intolerance – diarrhea and flatulence
•Small bowel bacterial overgrowth – bloating, diarrhea
•Microscopic colitis
•profuse, watery, non-bloody diarrhea
•4% of patients with celiac
• Is it another autoimmune disorder?
• Is it IBS?
Persistent Symptoms on a GFD
Dominica Gidrewicz, MD
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•Children with IBS have 4-fold higher prevalence of celiac 1
•30% of pt with CD adherent to GFD have IBS symptoms 2
•5-fold higher prevalence of IBS, regardless of adherence, compared to controls 2
1 Cristofori et al. JAMA Pediatr 20142 Sainsbury A et al. Clin Gastro Hepatol 2013; 11: 359
Celiac and IBS Crossover
Dominica Gidrewicz, MD
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Gidrewicz D. et al. JPGN 2017; 64: 362-367.
Follow-up Serology on a GFD
Grp C (↑TTG, EMA negative)
P < 0.001
0.3
0.2
Cu
mu
lati
ve p
atie
nts
wit
h (+
) TT
G
6 12 302418 36
0.1
0
1.0
0.7
0.6
0.5
0.4
0.8
0.9Grp A (↑↑↑ TTG & EMA)
Grp B (↑↑ TTG & EMA)
Time since starting a GFDDominica Gidrewicz, MD
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Prevalence
FIRST DEGREE RELATIVES
Siblings > Children > ParentsFemales > Males
8-15 %
Singh P et al. Am J Gastro 2015; 110; 1539-1548.
Associated Conditions
Dominica Gidrewicz, MD
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Prevalence
FIRST DEGREE RELATIVES
Siblings > Children > ParentsFemales > Males
8-15 %
Singh P et al. Am J Gastro 2015; 110; 1539-1548.
•85% not likely to develop celiac
•The whole household should not simply go GF
•Screen all first degree relatives > 3 years of age
•Consider rescreening every 2-3 years if asymptomatic (no guidelines yet for following relatives)
Associated Conditions
Dominica Gidrewicz, MD
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Prevalence
Autoimmune thyroid disease 20-30%
Psoriasis 4.3%
Type 1 diabetes 4-6%
Sjogren’s syndrome 2.4%
Hujoel I et al. Celiac Disease Clinical Features & Diagnosis Gastroenterol Clin N Am 2019; 19-27.Husby et al. ESPGHAN guidelines for the diagnosis of coeliac disease JPGN 2012; 54: 136.
Autoimmune Conditions
Dominica Gidrewicz, MD
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1. Diagnosis: start with total IgA and IgA-TTG
2. Some children may qualify for a diagnosis without a biopsy if serology very high.
3. Fiber, vitamin D and Calcium intake important.
4. If symptom do not resolve discuss with your doctor.
5. Follow serology post-diagnosis, can take time to normalize.
6. Patients should be monitored for associated conditions.
7. Initial & follow up consultations with a Registered Dietitian with expertise in celiac disease and the GF diet
8. Recommend evidence-based resources and connect with the Canadian Celiac Association for ongoing support
Summary
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THANK YOU