The Spectrum Of Gluten Related Disorders Alessio Fasano, M.D. W. - - PowerPoint PPT Presentation
The Spectrum Of Gluten Related Disorders Alessio Fasano, M.D. W. Allan Walker Chair in Pediatric Gastroenterology and Nutrition Professor of Pediatrics Harvard Medical School Mucosal Biology and Immunology Research Center And Center for Celiac
Alessio Fasano, M.D.
Professor of Pediatrics Harvard Medical School Mucosal Biology and Immunology Research Center And Center for Celiac Research And Treatment Massachusetts General Hospital for Children
Only People With Celiac Disease Everybody
Kasarda D. J Agric Food Chem. 2013;61: 1155–1159.
Kasarda D. J Agric Food Chem. 2013;61: 1155–1159.
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Aegilops tauschii DD 14 chromosomes 50,000 genes
42 chromosomes 150,000 genes
28 chromosomes 100,000 genes
Kasarda D. J Agric Food Chem. 2013;61: 1155–1159.
Gliadin Glutenin Gluten (gliadin+glutenin)
Maiuri et al. Scand J
Shan L et al, Science. 2002; 297:2275-9. Lammer K et al, Gastroenterology 2008;135:194-204. Lammer K et al, Immunology. 2011;132:432-40
WK Dicke, 1905 - 1962 1st case of CD at UMB: 1938
MHC class II HLA (DQ2 and/or DQ8) are present in >95% of patients;
known;
a complete resolution of the autoimmune process that can be re-ignited following re-exposure to gluten
Most common age of presentation: 6-24 months
Rarely: Celiac crisis
resistant to oral Fe
calcifications
Most common age of presentation: older child to adult
Listed in descending order of strength of evidence
1960 1970 1980 1990 2000 2010 0.0 0.5 1.0 1.5
year CD prevalence (%)
0.21% 0.45% 0.93%
For the American general population adopting a gluten-free diet is becoming an increasingly popular solution. The market for gluten-free food and beverage products grew at a compound annual growth rate of 28 percent from 2004 to 2011, to finish with almost $6.7 billion in retail sales last year. By the end of 2016 the market is expected to reach about $14.6 billion in sales.
Percentage of U.S. Adults Trying to Cut Down or Avoid Gluten in Their Diets Reaches New High in 2016, Reports NPD
Based on internet interview users age 18y+ who eats GF food Approx 50M Approx 24M Approx 7M Approx 9M
Approx 400,000
GLUTEN FREE DIET CONSUMERS MEDICAL NECESSITY WHEAT ALLERGY (IGE-MEDIATED) (~0.1%) CELIAC DISEASE (AUTOIMMUNE- BASED) (~1%) GLUTEN SENSITIVITY (INNATE IMMUNITY?) (??) NO MEDICAL NECESSITY
Cases of reaction to ingestion of gluten-containing grains in which both allergic and autoimmune mechanisms have been ruled out (diagnosis by exclusion criteria)
has been ruled out;
allergy symptomatology;
relapse after re-exposure to gluten-containing grains (double blind)
Sapone A. et al BMC Med 2012, Ludvigsson JF et al Gut 2013, Catassi C. Et al, Nutrients 2013
Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, Kaukinen K, Rostami K, Sanders DS, Schumann M, Ullrich R, Villalta D, Volta U, Catassi C, Fasano A. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC
Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C. The Oslo definitions for coeliac disease and related terms. Gut. 2013 Jan;62(1):43-52 Catassi C, Bai JC, Bonaz B, Bouma G, Calabrò A, Carroccio A, Castillejo G, Ciacci C, Cristofori F, Dolinsek J, Francavilla R, Elli L, Green P, Holtmeier W, Koehler P, Koletzko S, Meinhold C, Sanders D, Schumann M, Schuppan D, Ullrich R, Vécsei A, Volta U, Zevallos V, Sapone A, Fasano A. Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders. Nutrients. 2013 Sep 26;5(10):3839-53. Catassi C, Elli L, Bonaz B, Bouma G, Carroccio A, Castillejo G, Cellier C, Cristofori F, de Magistris L, Dolinsek J, Dieterich W, Francavilla R, Hadjivassiliou M, Holtmeier W, Körner U, Leffler DA, Lundin KE, Mazzarella G, Mulder CJ, Pellegrini N, Rostami K, Sanders D, Skodje GI, Schuppan D, Ullrich R, Volta U, Williams M, Zevallos VF, Zopf Y, Fasano A. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria. Nutrients. 2015 Jun 18;7(6):4966-77. doi: 10.3390/nu7064966.
Frequency Intes'nal Extra-intes'nal
Very Common Bloa-ng Lack of wellbeing Abdominal pain Tiredness Common Diarrhea Headache Epigastric pain Anxiety Nausea Foggy mind Aerophagia Numbness GER Joint/muscle pain Aphtous stoma--s Skin rash/derma--s Alterna-ng bowel habits Cons-pa-on Undetermined Hematochezia Weight loss Anal fissures Anemia Loss of balance Depression Rhini-s/asthma Weight increase Inters--al cys--s Ingrown hairs Oligo or polimenorrhea Sensory symptoms Disturbed sleep paMern Hallucina-ons Mood swings Au-sm Schizophrenia
The Salerno NCGS diagnostic criteria (Nutrients, 2015)
Chr hronic
Headache he Shor hort Memor emory Los Loss Anxiet nxiety Depr epres ession ion ADHD HD? Aut utis ism? m? Ataxia axia Seiz eizur ures es Schiz hizophr
enia? Irrit itabilit bility
Are The Epidemics Of Autism, ADHD and Schizophrenia Also Related to The Rise of Non-Celiac Gluten Sensitivity?
Biomarkers
YES YES NO
Gluten Related Disorders Pathogenesis Autoimmune Allergic Not Autoimmune Not allergic (Innate immunity?) Celiac Disease Gluten Ataxia Dermatitis herpetiformis Wheat allergy Gluten sensitivity Respiratory Allergy Food Allegy WDEIA Contact Urticaria Symptomitic Silent Potential
Proposed New Classification of Gluten Related Disorders
Differential Diagnosis Between CD, GS, and WA
Celiac Disease Gluten Sensitivity Wheat Allergy
Time interval between gluten exposure and
Weeks-Years Hours-Days Minutes-Hours Pathogenesis Autoimmunity (Innate+ Adaptive Immunity) Immunity? (Iinnate Immunity?) Allergic Immune Response HLA HLA DQ2/8 restricted (~97% positive cases) Not-HLA DQ2/8 restricted (50% DQ2/8 positive cases) Not-HLA DQ2/8 restricted (35-40% positive cases as in the general population) Auto-antibodies Almost always present Always absent Always absent Enteropathy Almost always present Always absent (slight increase in IEL) Always absent (eosinophils in the lamina propria) Symptoms Both intestinal and extra-intestinal (not distinguishable from GS and WA with GI symptoms) Both intestinal and extra- intestinal (not distinguishable from CD and WA with GI symptoms) Both intestinal and extra- intestinal (not distinguishable from CD and GS when presenting with GI symptoms) Complications Co-morbidities Long term complications Absence of co-morbidities and long term complications (long follow up studies needed to confirm it) Absence of co-morbidities. Short-term complications (incliuding anaphylaxis)