Celiac Disease. Gluten-Sensitive Enteropathy Celiac Sprue Non-tropical Sprue
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1 Celiac Disease Gluten-Sensitive Enteropathy Celiac Sprue Non-tropical Sprue
2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.
3 Overview History Presentation Associated diseases Diagnosis Non-celiac gluten intolerance Treatment Outcome
4 Celiac Disease What is it? Immune mediated enteropathy Triggered by ingestion of gluten In genetically susceptible individual Small bowel biopsy findings Resolution with gluten withdrawal
5 Pathology Villous atrophy of small intestine mucosa, worst proximally
6
7 History 150 AD, Aretaeus the Cappadocian Diarrhea of a chronic nature
8 -1887, Samuel Gee To regulate the food was the main part of the treatment (1quart of mussels per day) -1924, Sidney Haas (Banana diet)
9 1940 s, Willem Dicke, Dutch pediatrician Celiac patients paradoxically improved with shortages of grain during WWII Relapsed when bread parachuted in Gluten identified as toxic agent 1954 first duodenal biopsies via Crosby capsule 1970 s Endoscopic biopsies 1980 s Serologic testing
10 Epidemiology Whites of North European ancestry Female:male 2:1 Prevalence 1:150 to 1:300 US blood donors 1:250 Danish blood donors 1:300 Finnish blood donors 1:99 Italian school children 1:184
11 Age-adjusted Incidence of Celiac Disease in Olmsted County Rewers. Gastroenterology 2005; 128: S47
12 Family History Risk if first degree relative 17% Risk if HLA-identical sib 40% Risk if monozygotic twin 75% World J Gastro 2014; doi.org/ b
13 Pathogenesis Immune disorder: HLA-DQ2, HLA-DQ8 Plus abnormal diabetes susceptible locus chromosome 15q26 (autosomal recessive) Plus environmental trigger (gliadin) Activation of gluten-sensitive T-cells with subsequent inflammatory reaction causing mucosal damage
14 Pathogenesis of Celiac Disease
15 Presentation Clinical disease Subclinical disease
16 Clinical Iceberg of Celiac Disease
17 The Spectrum of Celiac Disease
18 Spectrum of Pathology and Malabsorption in Celiac Disease
19 Presentation Classic Villous atrophy Malabsorption Atypical most common Villous atrophy Subclinical malabsorption Silent Potential Immunologic abnormalities with no or normal biopsy
20 Classic, Non-classic or Absent Symptoms in Celiac BMC Gastro 2014; 14: 194
21 Variable Symptoms in Celiac Disease (n= 770) BMC Gastro 2014; 14: 194
22 Clinical Weight loss (30% are over weight) Diarrhea (<50%) Malabsorption Dermatitis herpitiformis Osteoporosis
23 Celiac Disease Laboratory Findings (that may arouse suspicion) Anemia iron deficient most common Folate deficiency, less often B12 hyposplenism Mildly abnormal transaminases Low albumin Elevated INR from Vit K deficiency Low Calcium/Phosphorus/Magnesium
24 Celiac Disease Extraintestinal presentations Fatigue, malaise Osteopenia/osteoporosis Arthritis in 22% - peripheral or axial Infertility Skin: Dermatitis Herpetiformis Mouth ulcers Neuropsychiatric - ataxia, depression, anxiety, epilepsy
25 Dermatitis herpetiformis Symmetric intensely pruritic papules and vescicles
26 Dermatitis herpetiformis
27 Celiac Disease Associated Immune Conditions Type I Diabetes (2-8%) Dermatitis herpetiformis Autoimmune thyroid disease Rheumatoid arthritis Systemic Lupus Autoimmune hepatitis Addison s disease Recurrent aphthous ulcerations Sjogren s syndrome Sarcoidosis Vitiligo Alopecia areata IgA deficiency Psoriasis Myesthenia gravis
28 Associated Conditions IgA deficiency 2% of celiacs (8% of IgA deficients will be celiac) Down syndrome 16% Hepatitis Osteoporosis Microscopic colitis (4%) Neuropsychiatric Arthritis
29 Abnormal Liver Chemistry in Celiac Disease Am J Gastro 2015; 110: 1216
30 Age-Specific Fertility Rates in Celiac Disease Tata. Gastroenterology 2005; 128: 849
31 Pregnancy Related Outcomes in Celiac Disease Tata. Gastroenterology 2005; 128: 849
32 Cancer Incidence in Celiac or Dermatitis Herpiformis (n=12,000) F/U (yrs) Lymphoma Oral Esophagus Small Bowel Colon Liver 1-4 (CI) 9.7 ( ( ) 3.6 (0.4-13) 13 (3.6-34) 2.4 ( ) 0.6 ( ) >5 (CI) 3.8 ( ) 2.8 ( ) 4.7 (1.3-12) 8.3 (2.3-21) 1.5 ( ) 4.1 ( ) Askling. Gastroenterol 2002; 123: 1428
33 Serum Testing for Celiac Diagnosis Small bowel biopsy on gluten diet (proximal and distal duodenum) Sensitvity Specificity IgA anti ttg Ab >95% >95% First level screening IgG anti ttg Ab 13-96% % If IgA deficient Anti endomysial Ab >90% 98% HLA-DQ2 or HLA-DQ8 91% 54% High negative predictive value Response to gluten free diet (symptoms, ttg, biopsy)
34 CELIAC DISEASE Endoscopy
35 CELIAC : Histology NORMAL CELIAC DISEASE
36 Serology in Celiac Disease Sensitivity (%) Specificity (%) IgA endomysial Ab IgA ttg Ab IgA antigliadin Ab IgG antigliadin Ab
37 Genetic Markers in Celiac HLA DQ 2 and 8 All celiac patients will be HLA DQ2 or DQ8 positive
38 Who Should be Tested Classic GI symptoms: chronic diarrhea, weight loss, malabsorption, IBS-D Unexplained other diseases: delayed puberty, infertility, fetal loss, elevated AST,iron deficiency anemia High risk individuals: first degree relatives, type I diabetes, Down syndrome
39 Treatment Lifelong gluten free diet (ie avoid wheat, rye, barley and?oats) Dietitian consult Support group (?) Specific nutrient replacement Screening for bone loss Pneumococcal vaccination (hyposplenism) (Screening of first degree relatives)
40 Gluten Free Diet A chronic treatment, not a cure The illness is difficult to cure even a slight dietetic error can lead to relapse Aretaeus, 50 AD
41 Treatment Burden in Celiac Disease Am J Gastro 2014; 109: 1304
42 Gluten Normal diet = 10,000 mg gluten/day 1 slice bread = 2,000 mg 1/40 slice bread = 50 mg Gluten challenge 3gm/day (2 slices wheat bread) for 8 (?2) weeks Gluten free diet < 10mg/day
43 Non-Celiac Gluten Intolerance
44 A Gluten-Free for all 18% Americans follow gluten free diet Gluten free sales in USA 2012 $4.2b increasing to $6.6b by 2017 Wall St Journal Nov 8, 2013
45 US Sales of Gluten-Free Products New Scientist July 12, 2014
46 Gluten Causes GI Symptoms in subjects Without Celiac Disease A Double Blind Placebo Controlled study Biesiekierski. Am J Gastro 2011; 106: 508
47 Wheat More than Gluten FODMAPs (Fructans) Wheat-germ agglutinin Amylase trypsin inhibitors Gluten Nat Rev Gastro Hep 2015; 12: 516
48 Am J Gastro 2014; 109: 741
49 Celiac Complications Malabsorption Non-responsive celiac disease Malignancy Small bowel lymphoma Small bowel adenocarcinoma
50 Complications Malabsorption Osteoporosis Iron deficiency Hyposplenism Impaired immunity Pneumococal vaccination?
51 Longterm Survival with Celiac Disease 9,133 healthy Air Force recruits % with celiac (+ttg) Mortality hazard ratio = 3.9 (95% CI, ) Rubio-Tapia Gastroenterol 2009; 137: 88
52 Increased Mortality Rate for Symptomatic Celiac Disease Nat Rev Gastro Hep 2010; 7: 158
53 Causes of Death in People with Celiac Disease No different (n= 10,825) Gut 2015; 64: 1220
54 Why should we detect celiac disease? Cancer risk Lymphoma risk Infertility Adverse pregnacy outcome Osteoporosis Nutritional deficiencies
55 Controversies & Challenges Diagnosis in patient already on gluten free diet Repeat ttg? Half life of ttg 6-8 weeks Repeat follow-up biopsy? May take months for histologic recovery Non-responder
56 Screening General Population Not advised USPSTF. JAMA 2017; 317: 1252 B Soc Gastro. Gut 2014; 63: 1210
57 Celiac Disease Summary Suspect Screen Small bowel biopsy Start lifelong gluten avoidance Search for complications especially from malabsorption: osteoporosis, anemia
58 References Diagnosis and Management of CD. Guidelines from BSG. Gut 2014; 63: 1210 The spectrum of noncoeliac gluten sensitivity. Nat Rev Gastro 2015; 12: 516 ACG Clinical guidelines: Diagnosis and management of celiac disease. Am J Gastro 2013; 108: 656 Celiac disease. NEJM 2012; 367: 2419 From coeliac to noncoeliac gluten sensitivity. Curr Opin Gastro 2016; 32: 120 Celiac disease and nonceliac gluten sensitivity. JAMA 2017; 318: 647
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