Celiac Disease Gluten-free and still sick What s going on?
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1 Celiac Disease Gluten-free and still sick What s going on? Keith J. Laskin, MD Medical Director, The Celiac Center at Paoli Hospital Main Line Gastroenterology Associates, PC March 15, 2013
2 Samuel Gee Celiac Disease 1888 What was known then
3 Samuel Gee Celiac Disease 1888 What was known then
4 Dr. Willem-Karel Dicke s - WWII bread shortage Dicke, et al. Role of gluten
5 Definition: Celiac Disease Autoimmune disease Specific trigger Genetically predisposed Damage to the intestine Variety of gastrointestinal symptoms and non-intestinal symptoms Associated with many other conditions Fully reversible
6 What else do we know? Prevalence 13,145 subjects screened Fasano et al., Arch Int Med 2003 Healthy individuals 1:133 At-risk population 1st degree 1:22 2nd degree 1:39 Symptomatic adults 1:68 Symptomatic children 1:25
7 Celiac Disease in Perspective Celiac Disease Epilepsy Rheumatoid arthritis Systemic lupus Parkinson s disease 3 million 2.7 million 2.1 million 1.5 million 1.0 million Diabetes, Type 1 700,000 Crohn s disease 700,000 Ulcerative colitis 700,000 Multiple sclerosis 400,000 Cystic fibrosis 30,000 Hemophilia 17,000
8 What else do we know? Trigger Autoimmune disease Specific trigger
9 What else do we know? Changing presentation 1930s 2000s
10 Classical Symptoms Diarrhea Gas / bloating Weight loss
11 Atypical Symptoms Iron deficiency Osteoporosis Constipation Neuropathy / ataxia Fatigue Elevated LFTs Indigestion Skin rash Infertility/miscarriages
12 Changing Presentation of Celiac Disease Pre 1993 Post 1993
13 Symptoms in Children Food avoidance ADD/ADHD, difficulty concentrating Short stature / delayed growth / delayed puberty Abdominal pain / distension Dental anomalies Hypoplastic enamel Delayed eruption
14 Celiac Disease is BECOMING MORE COMMON 4.5x
15 Celiac Disease is BECOMING MORE COMMON Prevalence DOUBLES every 15 years
16 Population Projection Chester County, PA
17 Celiac Disease Projection Chester County, PA
18 Why is the prevalence increasing? Feb 23, 2013 Not enough breastfeeding Too much gluten Not enough dirt 18
19 1:100 Karelia 1:500 Background. The populations in adjacent Russian Karelia and Finland are equally exposed to grain products and share partly the same ancestry, but live in completely different socioeconomic environments. Conclusions. The prevalence of transglutaminase antibodies and celiac disease is lower in Russian Karelia than in Finland. This may be associated with a protective environment characterized by inferior prosperity and standard of hygiene in Karelia.
20 3 Treatments for Celiac Disease Gluten-free diet Gluten-free diet Gluten-free diet
21 Celiac Disease, Gluten-Free, and STILL Sick?? Nonresponsive Celiac Disease
22 Nonresponsive Celiac Disease Persistent, or recurrent symptoms Despite GFD for 6-12 months
23 Nonresponsive Celiac Disease Why does this happen?
24 Nonresponsive Celiac Disease Is it really celiac disease? Diagnosis based on: Clinical symptoms Blood testing Tissue sample (biopsy)
25 Nonresponsive Celiac Disease Is it really celiac disease? Diagnosis based on: Clinical symptoms Blood testing Tissue sample (biopsy)
26 Celiac Disease Clinical symptoms often non-specific Irritable bowel syndrome A. Fasano, N Engl J Med 2003;348:
27 Nonresponsive Celiac Disease Is the diagnosis correct? Diagnosis based on: Clinical symptoms Blood testing Tissue sample (biopsy)
28 Testing for Celiac Disease Blood tests Sensitivity % Specificity % Antigliadin IgG Antigliadin IgA Antiendomysial TTG IgA Farrell RJ, and Kelly CP. Am J Gastroenterol 2001;96:
29 Celiac Disease Blood tests may be erroneous Test Sensitivity Specificity PPV* NPV* AGA-IgA AGA-IgG EMA-IgA TTG-IgA TTG-IgG DGP-IgA DGP-IgG DGP-IgA/IgG Leffler and Schuppan, Am J Gastroenterol 2010;105:
30 Nonresponsive Celiac Disease Is the diagnosis correct? Diagnosis based on: Clinical symptoms Blood testing Tissue sample (biopsy)
31 Testing for Celiac Disease Value of tissue samples Celiac Disease villous damage, IEL, crypt hyperplasia
32 Testing for Celiac Disease Value of tissue samples - not definitive Celiac Disease villous damage, IEL, crypt hyperplasia Tropical sprue Viral enteritis Autoimmune enteropathy Giardia infection Cryptosporidiosis Microsporidiosis Bacterial overgrowth Food allergies Crohn s disease Combined variable immunodeficiency NSAIDs H pylori infection
33 Diagnostic Uncertainty Clinical symptoms not specific Blood tests not definitive Tissue samples may have subtle changes, or look identical to abnormalities found in other conditions
34 3 Most Common Reasons for NRCD Gluten ingestion Gluten ingestion Gluten ingestion
35 Nonresponsive Celiac Disease % Abdulkarim,AS Am J Gastro 2002
36 Nonresponsive Celiac Disease % Leffler, et al. Clin Gastro Hep 2007:5;
37 Mechanisms of Gluten Contamination Intentional Accidental Other???
38 Intentional Gluten Contamination Availability and cost of GF food
39 Food Cost Comparison Regular Gluten-Free Price per ounce Bread Cereal Waffles Crackers Cookies Pretzels Pasta Pizza Macaroni Cake Lee, J Hum Nutr Diet 2007;20:423
40 Intentional Gluten Contamination Availability and cost of GF food Quality of GF food
41 Satisfaction With GFD 75% Aziz I et al., J Gastrointestin Liver Dis 2011
42 Intentional Gluten Contamination Availability and cost of GF food Quality of GF food Difficulty eating out and traveling
43 Intentional Gluten Contamination Availability and cost of GF food Quality of GF food Difficulty eating out and traveling Social issues
44 Intentional Gluten Contamination Social exclusion/isolation
45 Accidental Gluten Contamination Inadvertent Gluten RESTAURANT FOOD
46 Accidental Gluten Contamination Gluten in Medications CELIAC-1
47 Accidental Gluten Contamination NEJM 2007
48 Accidental Gluten Contamination
49 Gluten Contamination Elimination Diet Gluten Contamination Elimination Diet 82% improved with GCED 80% of those improved were able to resume normal GFD Hollon, et al. BMC Gastroenterology 2013,13:40
50 Gluten Contamination Mechanisms Intentional Accidental Other???
51 Other Gluten Contamination Naturally GF Foods Fruits and vegetables Plain dairy products Fresh meat, poultry, fish, and eggs Plain legumes, nuts, seeds Rice, corn, potatoes, quinoa, buckwheat, sorghum Water, most coffees, some teas, juices, most sodas, wines & distilled alcohols
52 Gluten-Contaminated Safe Grains
53 Gluten Free and Still Sick? What about FODMAPs Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols Lactose (milk products) Fructose (apples, pears, honey) Fructans (wheat, rye, garlic, onions) Galactans (cabbage, legumes) Polyol sweeteners (sorbitol, xylitol, mannitol, isomalt)
54 Gluten Free and Still Sick? FODMAPs Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols
55 Are FODMAPs The Problem? Careful dietary history Breath testing: LACTOSE and FRUCTOSE Elimination diet: Eliminate all FODMAPs for 6-8 weeks Add each individual FODMAP back into diet one at a time Usually don t need to completely avoid the offending FODMAP
56 Gluten Free and Still Sick? Other possibilities Irritable Bowel Syndrome very common SIBO (bacterial overgrowth) / intestinal dysbiosis common Intestinal dysbiosis - common Microscopic colitis somewhat common (lymphocytic colitis, collagenous colitis) Inflammatory bowel disease Pancreatic insufficiency - rare Food allergy very rare Cancer very rare Refractory Celiac Disease extremely rare
57 Gluten Free and Still Sick? Refractory Celiac Disease Ongoing symptoms (weight loss, steatorrhea) in association with intestinal damage Despite strict GFD No identifiable cause Negative TTG or EMA (often)
58 Gluten Free and Still Sick? Refractory Celiac Disease Two main types RCD Type I normal intestinal lymphocytes Better prognosis 5-year survival: ~90-100% RCD Type II abnormal intestinal lymphocytes Worse prognosis Higher risk of intestinal cancer 5-year survival: ~50%
59 Gluten contamination elimination diet Celiac Disease Evaluation of Nonresponders Nonresponsive CD No Celiac Disease Gluten Ingestion Lactose/fruc intol, SIBO Microscopic colitis, IBD Pancreatic insuf, IBS Food allergy, cancer Refractory CD Gluten in diet Abnormal Abnormal Response Abnormal Review diagnosis CD Expert dietary review GFD Breath testing/diet trial Negative Colonoscopy Normal Empiric treatment No response Misc tests Normal
60 Save the Date Celiac Awareness Day Lankenau/Paoli 8 Community screening Lecture series Dr. Peter Green Dr. Steven Plogsted Anne Lee, RD, MA, LDN
61 Save the Date
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