Celiac Disease: Pop quiz
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- Winifred Moore
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1 BIDMC Celiac Disease: Pp quiz HMS The Wrld View f Celiac Disease circa 1990 Celiac disease is: True r? 1. An uncmmn cnditin in the US (~1:5000) that is mre cmmn in Eurpe (~1:500) 2. Usually presents with severe diarrhea and malabsrptin 3. Usually a pediatric diagnsis 4. Diagnsed by clinical imprvement fllwing treatment with gluten free diet Nrth America 1/5000 Ireland 1/300 Suth America Africa Asia Eurpe 1/1000 Kelly CP. Celiac Disease & Refractry Celiac Disease. Sleisenger & Frdtran s GI & Liver Disease, 10 th editin, in press Tday s Wrld View f Celiac Disease Cmmn & Nt Limited t Eurpeans Celiac disease at BIDMC Bstn Patient and Visit Vlumes 1997 t 2012 Americas & Eurpe ~1% [0.6 t 2.5%] Finland: ~2.5% Nrthern India?3% Patient Fld Individual Year Visits increase Patients Treated ~1% in US (> 3 millin) SuthEast Asia TTG use increases , Subsaharan Africa Australia ~1.5% , , , , , , , , , ,222 Kelly CP. Celiac Disease & Refractry Celiac Disease. Sleisenger & Frdtran s GI & Liver Disease, 10 th editin, in press Increased Prevalence Over Time in U.S.A. (in Line with Other Autimmune Diseases) 0.21% 0.45% 0.93% During the past 35 years the true prevalence f CD in USA dubled every 15 years. C. Catassi et al, Annal Med (n line ahead f print) Celiac Disease: Age f presentatin Classically after weaning Peak #1: 4 t 7 years Symptms ften imprve during adlescence Celiac hneymn Can present fr the first time at any age Mst cmmn - Peak #2: 30 t 50 years BIDMC means: 46 years - age at diagnsis 11 years interval frm symptm nset t diagnsis 6 years - interval frm presentatin t diagnsis
2 The prtean clinical manifestatins f celiac disease Can presenting at any age t any medical specialty The clinical spectrum f Celiac Disease #1 Cnsider a diagnsis f celiac disease IgA TTG psitive ~1% Mucsal abnrmality Ptential CD ~0.1% Genetic susceptibility (HLA DQ2 r DQ8) ~40% Classical CD ~0.1% Atypical CD ~0.5% Silent CD ~0.4% Healthy individual The celiac iceberg RJ Farrell, CP Kelly N Engl J Med 2002; 346:183 Wh? Diversity f celiac disease: Glbal, multiple symptms, any age Cmmn in many ethnic backgrunds When? Any age after gluten ingestin Average age at diagnsis ~45 yrs Hw? Highly diverse presentatins. Average 11 years f symptms prir t diagnsis Green AJG 2001, Cranney DDS 2007 Wh t test Refractry fr celiac Sprue disease Diarrhea +/- malabsrptin IBS-like (especially D-IBS) Lactse (r fructse) Intlerance-like but nt respnding fully t dietary measures Nutritinal deficiencies Other Irn deficiency anemia (mst cmmn) B12, Flate (nw rare) Vit D / stepenia/steprsis Dermatitis Herpetifrmis Impaired fertility CNS: Ataxia, peripheral neurpathy Severe aphthus stmatitis Abnrmal LFTs Hw t diagnse Celiac disease 1. Specific celiac serlgy IgA ttg (tissue TransGlutaminase) the single best test IgG ttg less sensitive than IgA ttg IgA DGP (Deamidated Gliadin Peptide) IgG DGP mst accurate IgG-based assay Ttal IgA ptinal (IgG DGP mre accurate) 2. Characteristic histlgy (EGD with bipsy) Rubi-Tapia et al. ACG Clinical Guidelines n 12 Celiac Disease. Am J Gastrenterl Hw NOT t diagnse Celiac disease Cmmn Pitfalls: Clinical respnse t GFD Psitive serum IgG r IgA anti-gliadin antibdies Psitive fecal anti-gliadin antibdies HLA DQ2 r DQ8 psitivity (required but nt sufficient) Flawed interpretatin f bipsy histlgy: Villus distrtin and inflammatin in dudenal bulb Increased IELs [intraepithelial lymphcytes] Villus atrphy frm anther cause (TTG & DGP negative)
3 Is small intestinal bipsy still needed t diagnse celiac disease? Treatment Mther knws f Celiac best Disease cntinued Yes because: Celiac disease is defined by enterpathy Bipsy is relatively simple and safe psitive serlgy des ccur A false psitive diagnsis is very cstly in terms f the patient s lifelng treatment burden Symptm respnse t GFD is nt reliable fr diagnsis The diagnsis cannt be cnfirmed r refuted easily after treatment with a GFD (gluten free diet) Management Mther knws f Celiac best cntinued Disease Celiac Disease: Respnse t GFD NIH Celiac Disease Cnsensus Cnference 2004 ttg IgA > 100 units ttg IgA nrmal [<20 units] Cnsultatin with a skilled celiac dietician Educatin abut the disease Lifelng adherence t a gluten-free diet Identificatin & treatment f nutritinal deficiencies Access t a supprt and advcacy grup Cntinuus lng-term fllw up by a multidisciplinary team Small intestinal villus atrphy & crypt hyperplasia Reslutin f intestinal injury n gluten free diet Nn-Respnsive Celiac Disease Mst patients with CD respnd well t GFD ~10% are nn-respnsive: Primary: Onging symptms, signs r lab. abnrmalities f CD after > six mnths f gluten withdrawal Secndary: Recurrence f symptms, signs r lab. abnrmalities f CD after an initial respnse and while still n a strict GFD fr > 6 mnths Other included: Peptic ulcer disease (2), Crhn s disease (1), Dudenal adenca (1), Fd allergy (1), Gastrparesis (1) Other 8% Refractry Sprue 11% IBS 18% >10 times mre likely if TTG elevated after >12 mnths n GFD Gluten Expsure 35% Primary & Secndary: Similar frequency Similar demgraphics Small Intestinal Bacterial Overgrwth 6% Eating Disrder 6% Disaccharidase Deficiency 9% Micrscpic Clitis 7%
4 Gluten where will it hide next? Tthpaste Envelpe gum Lipstick Candy Flavrings Medicatins Vitamins & supplements Safe gluten-free grains Thmpsn et al. J Am Diet Assc 2010;110:937 Gluten Tiny gluten expsures perpetuate active disease where will it hide next? Histlgy pst 90 day, 50 mg gluten/day micrchallenge Villus height: Crypt depth Nrmal diet ~10,000 mg /day Slice f bread ~2,000 mg 1/40 th slice f bread ~50 mg P = 0.03 Celiac Catassi et al. Am J Clin Nutr 2007;85(1): Hw t Evaluate GFD adherence Patient self-reprt CDAT a Validated GFD adherence measure Frequency f cheating & Cnfidence in ability t fllw GFD when dining ut Serlgy fcus n trajectry nt abslute values expect 50% drp every 2-4 mnths NOT sensitive t dietary gluten Expert dietician evaluatin = gld standard Bipsy histlgy - a measure f disease activity nt GFD adherence Measure gluten in fd, stl & urine Leffler et al. Clin Gastrenterl Hepatl 2009;7: Risk f neplasia in celiac disease Sweden in patient register 1964 t ,019 with CD 1,580 with DH * Standardized incidence rati (SIR) fr neplasia SIR in DH 1.2 Risks declined with time and duratin f fllw up Askling et al. Gastrenterl 2002;123: Site SIR Celiac % f chrt All sites 1.3* 2.3% Oral % Esphagus % Small intest % Cln % Lymphma % Hdgkin s % NHL % D we need nn-dietary treatments fr Celiac Disease? 24 The GFD is highly effective in celiac disease BUT: > 10% Nn-respnsive t GFD 1-2% Refractry t GFD ~ 30% f adults n GFD fr celiac disease have nging partial villus atrphy n bipsy 70% f Celiac Disease Patients Reprt Gluten Expsures n GFD Strict GFD difficult t maintain At scial events Fr fd prepared utside the hme When travelling In restaurants & cafeterias Take-ut Sanders JGLD 2011 Fr the elderly Fr the illiterate Fr thse with mental r psychlgical impairment Reprted intentinal and inadvertent gluten cnsumptin (n=269) Hall NJ, Rubin GP, Charnck A, Intentinal and Inadvertent Nn Adherence in Adult Celiac Disease. A Crss-Sectinal Survey Appetite 68:56-62, 2013
5 Lw satisfactin with the GFD amngst patients with Celiac disease 26 Perceived treatment burden is very high in Celiac disease Sanders JGLD % 35% 23% Very pr Pr Average Gd Excellent Satisfactin with GFD Renal disease n Hemdialysis = 56.4 Celiac disease = 44.9 VAS Higher than: Insulin dependant diabetes Irritable bwel syndrme Cngestive heart failure Inflammatry bwel disease Hypertensin GERD Treatment Burden Celiac disease * 21.3* VAS: 0 = Very Easy 100 = Very Difficult *Cmpared with CeD, p<0.001 Shah S et al. Treatment burden in CeD. Am J Gastrenterl ;109: Scial islatin is part f the treatment burden f CeD 28 Patient respnses regarding: Scial islatin Burden f requesting and explaining GFD Inhibitin f scial interactins Market Research, Alba Therapeutics & Duble Helix Hmewrk Questin: What having celiac disease means t yu? Pathgenesis f Celiac Disease & Wheat Ptential Sites fr Interventin Barley Rye Gluten / gliadin 1. Ingested Gluten free diet 2. Survives digestin Glutenases 3. Crsses gut lining Tight junctin mdulatr 4. Made tastier by TTG Laraztide acetate 5. Taken up by antigen presenting cells (APCs) 6. Genetically encded DQ2 r DQ8 present 7. Presented n DQ2/8 8. T cells activated Induce immune tlerance / desensitizatin Inflammatin Anti-inflammatry: Antibdy prductin Sterid prednisne, budesnide Tissue damage Mesalamine Immune mdulatin AZA, anti-il-15 Farrell & Kelly N Engl J Med 2002;346:183 Small bwel bipsy f patients with diarrhea & blating Nrmal Villus atrphy Which persn can t eat gluten? Neither can tlerate it Epidemilgy f Celiac Disease & Use f the Gluten free Diet in the US Rubi-Tapia A et al. Am J Gastrenterl Oct;107(10): ; Celiac disease Serprevalence 0.71%; >2 millin On Gluten Free Diet ~2 millin Diagnsed with celiac disease, and n a gluten free diet ~300,000 Slide Atlas f Gastrnterlgy, Misiewicz et al, 1984 Mst peple in the US with CeD remain undiagnsed NCGS may be very cmmn
6 Nn celiac Gluten Sensitivity: The new kid that s taking ver the blck? Prs: Mre awareness f GFD Easier access t GFD Lwer csts?? 32 Cns: Incnsistencies regarding strictness Cnfusin regarding a lifestyle ptin versus a medically prescribed and required diet New Yrker cartn by GREGORY Celiac disease vs NCGS Wh cares? r Des it even matter? Gluten expsure Implicatins fr family Cmplicatins Lng-term management Celiac disease < 20 ppm Relatives at high risk (esp. 1 st degree) Malignancies incl. Lymphma Nutritinal deficiencies Recmmended NCGS [Nn-celiac gluten sensitivity] Variable Titrate t symptms Nne Nne Nt needed Diagnstic Testing in Celiac disease (CeD) versus Nn-celiac Gluten Sensitivity (NCGS) Celiac Disease: Respnse t GFD Finding Symptms after gluten ingestin Specific CeD serlgies Villus atrphy (bipsy changes) Celiac genes (HLA DQ2/8) Untreated CeD Treated CeD (n GFD) NCGS Yes Yes Yes Yes N (ften) N Yes N (ften) N Yes Yes N in ~40% Am J Gastrenterl : PMID: Main pints: 1. Psitive serlgy (TTG, EMA r DGP) at any time - high PPV fr Celiac disease 2. Negative serlgy while n nrmal diet - high NPV 3. HLA DQ2 & 8 negative essentially excludes Celiac disease 4. Gluten challenge smetimes needed ACG Clinical Guidelines. Am J Gastrenterl The many faces f Celiac Disease Cmmn (~1% f ppulatin) Cmplex presentatins All ages With r withut GI symptms Deficiency states esp. irn deficiency Easy t diagnse (r exclude) prir t GFD by IgA-tTG (plus bipsy if psitive) GFD is the nly treatment Usually effective Often cnsidered burdensme Increasingly ppular espfr Nn-celiac gluten sensitivity Nn-dietary treatments under investigatin
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