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Description : This medical presentation titled ""Gluten - Going against the grain-The celiac patient"" tells us about celiac disease, an autoimmune mediated small bowel enteropathy caused by the ingestion of gluten.

Tags : Gluten, celiac disease, autoimmune, bowel enteropathy, ingestion, Celiac Sprue, Gluten-Sensitive Enteropathy, Immune Response, Dermatitis Herpetiformis, Diagnosis, Upper Endoscopy, Pathology,

Published on : Apr 24, 2021 | Views : 2119 | Downloads : 6

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Slide 1-

Gluten…Going against the grain-The celiac patient Kim Hiser, APRN, DNP
Slide 2-

What is Celiac disease? Celiac disease is an autoimmune mediated small bowel enteropathy caused by the ingestion of gluten
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But… It’s NOT A Wheat Allergy IgE Mediated food allergy It’s NOT Fructan Sensitivity Gastrointestinal symptoms related to ingesting fructans. Associated with IBS It’s NOT Gluten Sensitivity GI or systemic symptoms that improve on a gluten free diet in those who do not meet diagnostic criteria for CD
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Other TERMS… Previously known as Celiac Sprue Gluten-Sensitive Enteropathy
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Prevalence In the US Celiac Disease occurs in approximately 1:133 persons Over 3,000,000 people in the US may have CD, only about 150,000 diagnosed More common in those with 1st degree relatives with CD ( as many as 1:22; 2nd degree 1:39) Most common in Caucasian and Northern European ancestry but increasing in other areas of the world African, Hispanic and Asian Americans 1:236 6% of people with Type 1 DM have CD 12% of people with Down Syndrome have CD 20% of people with collagenous colitis-CD
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World-Wide Prevalence
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The ONLY* treatment for Celiac Disease is COMPLETE lifelong avoidance of Gluten *(current)
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So what is gluten? Gluten is the protein found in wheat endosperm that nourishes plant embryos during germination and later provides the elasticity of the dough. Gluten is composed of two proteins: gliadin (a prolamin protein) and glutenin (a glutelin protein) True gluten is found in Wheat but Barley and Rye contain prolamin and glutelin proteins and therefore are also considered to contain gluten. Oats are cross-contaminated in processing facilities so must also be avoided. WBRO
Slide 9-

Autoimmune Disorder Genetically Susceptible Person A Diet containing gluten Environmental trigger Trauma/Stress (Pregnancy/illness) Celiac Disease
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Immune Response CD is only autoimmune disorder with an environmental trigger: Gluten Those with CD have the HLA-DQ2 or HLA-DQ8 gene loci α-gliadin stimulates membrane cells in the intestine (Enterocytes) to allow larger molecules around the seal between cells. Disruption of tight junctions allow peptides to enter. These gliadin peptides stimulate a T-Cell mediated immune response Anti-transglutaminase Antibodies to the enzyme tissue transglutaminase elevate and are measurable
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Immune Response
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Classification Symptomatic Disease 3 Features: Symptoms present (resolve with removal of gluten in diet), Villous Atrophy (mucosal damage resolves on GF diet), serologic markers positive Atypical Disease Display minor gastrointestinal complaints, severe mucosal damage, serologic markers positive Asymptomatic (silent) Disease No clinical symptoms, Mucosal damage present, serologic markers positive. Discover incidentally with screening (1st degree relative, Down Syndrome, DM type I) Latent Disease No symptoms, Normal mucosa, positive serology (may have had disease as a child, or will develop celiac disease later, latency may be transient)
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Manifestations Over 300 reported symptoms of CD Not everyone is symptomatic Gastrointestinal Symptoms: Diarrhea/constipation, foul-smelling BM, steatorrhea, flatulence, malabsorption, weight loss, severe iron deficiency anemia, vitamin D deficiency, deficiency in calcium, B12, abdominal pain, bloating, anorexia, aphthous stomatitis Non-Gastrointestinal Symptoms: Headache, peripheral neuropathy, ataxia, depression, dysthymia, anxiety, epilepsy, neurologic disorders from deficiencies in B vitamins, growth failure in kids/short stature, osteoporosis/osteopenia, arthritis, autoimmune diseases Less common: Cancers (small bowel lymphoma), “mental fog”, miscarriage, infertility
Slide 14-

Development of other Autoimmune Disorders After diagnosis of CD 2-4 years patient’s have 10.5% chance of developing other autoimmune disorders By age… Age Chance of other AI disorder 4-12 16.7% 12-20 27% >20 34%
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Dermatitis Herpetiformis Multiple intensely pruritic papules and vesicles in a herpetiform pattern seen on the elbows, knees, dorsal forearms, back and buttocks Common in CD Resolves with withdrawal of gluten in the diet (Can take several months)
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Diagnosis Often under diagnosed/misdiagnosed due to similarities with other conditions Growing number of non-celiac gluten sensitivity Serologic antibodies are abnormally elevated in those with CD (Immunoglobulin A anti-tissue transglutaminase (TTG IgA), anti-Gliadin Abs, Endomysial Abs Upper Endoscopy with small bowel biopsies find villous blunting and intraepithelial lymphocytosis (Gold Standard for diagnosis) Marsh Classification system of Immunopathology Genetic testing for HLA-DQ2 and HLA-DQ8 available
Slide 17-

Upper Endoscopy EGD with Small bowel biopsies:1-2 bulbar and at least 4 distal duodenal biopsies recommended Intraepithelial lymphocytosis and villous atrophy diagnostic of celiac disease Procedure performed on a gluten containing diet Gluten Challenge: 3 grams daily for 2 weeks before endoscopy
Slide 18-

Microscopic Image of Villi
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Pathology
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Classification Systems
Slide 21-

Serologic Testing TTG IgA has 95% Specificity and 98% Sensitivity for diagnosing CD Anti-Gliadin Abs are used to screen when IgA deficiency present Anti-Endomesial Abs 100% Specificity and 90% Sensitivity, a qualitative value that is variable and more subjective so used less often Celiac Disease Panel including all the above serologic screens are available.
Slide 22-

Avoidance Avoiding gluten is easier said than done! Patients need to Label Read-Everything It doesn’t stop at Label Reading-Even if the label does not identify gluten-most don’t… It can still contain gluten. Patients need to contact manufacturers to identify if products are gluten free
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Inadvertent Ingestion of Gluten At the time of diagnosis, patient’s will have varying degrees of mucosal damage in the intestine Partial villous healing is typically achieved at 3 months on a gluten free diet Some individuals will normalize there serologic markers by 3 months Full villous healing is typically achieved at 6 months on a gluten free diet Exception: Refractory Celiac Disease which may require steroids
Slide 24-

Why Treat? Usual elapsed time from symptoms to diagnosis is 10 years in the US Untreated disease increases risk of cancer (B and T cell Small bowel lymphomas) 8-10% CD with severe biopsies develop lymphoma; Diagnosis later in life=greater risk Untreated disease increases risk of miscarriage; 8% attributed to CD; infertility 4-8% cases 51.4% of those with celiac disease develop neurologic disorders (19.9% control). Total US healthcare cost for untreated CD per patient is $5,000-12,000 per year, and overall $14.5-34.8 billion annually 3.5% risk of osteoporosis (general population 0.05% risk)
Slide 25-

Monitoring after Diagnosis Remain on lifelong GF diet Some celiac patients have reactions to oats Up to 20% of those with CD remain lactose intolerant Evaluate for micronutrient deficiencies: Iron, folate, vitamin D and B12 deficiencies; Copper, Zinc deficiencies less common Bone density testing at baseline Serologic marker testing at 3 mo., 6 mo., yearly after normalized
Slide 26-

Gluten Free Sales From 2004-2005 GF sales increased by $77.8 million (14.6% growth) In 2015, sales $2.79 billion to $5 billion By 2020, $7.59 billion
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Determining gluten free Status FDA guidelines published final rule guidelines for labeling food items gluten free in August, 2013 ‘The final rule defines "gluten-free" as meaning that the food either is inherently gluten free; or does not contain an ingredient that is: 1) a gluten-containing grain (e.g., spelt wheat); 2) derived from a gluten-containing grain that has not been processed to remove gluten (e.g., wheat flour); or 3) derived from a gluten-containing grain that has been processed to remove gluten (e.g., wheat starch), if the use of that ingredient results in the presence of 20 parts per million (ppm) or more gluten in the food. Also, any unavoidable presence of gluten in the food must be less than 20 ppm.’ www.fda.gov
Slide 28-

Reading Labels 101 Not Easy Several different ways gluten free is identified- Symbols Different wording for Gluten Free Naturally Gluten Free food/No Gluten ingredients No wheat-not the same
Slide 29-

101 Continued… 1st: look for the words Gluten free on the packaging- if found product must be less than 20ppm of gluten per FDA standards 2nd: look for the words wheat, barley or rye- if present, don’t eat. 3rd: look for other common gluten containing ingredients ex. Breading, brewer’s yeast, bulgar, durum, graham flour, kamut, malt, vinegars, triticale 4th: Watch for common foods with gluten: beer, breads, broths, cereals, cookies/crackers, licorice/candies/chocolates, flavorings, seasonings, imitation seafood, processed foods, sauces/dressings, processed meats (deli meat, sausage), injected broth in meats, soy sauce Non-food sources of gluten: Medications both prescription and over the counter, makeup/lipstick, stamps and envelope glue If the label passes the test, it still could have been cross-contaminated in processing if made on the same line as gluten containing products.
Slide 30-

Lifestyle modification Cross-Contamination Cooking gluten-free items in similar containers with gluten containing items will expose to gluten Kitchen preparation Separate preparation surfaces, storage containers, toaster, cutting boards and strainers, plastic and wooden items Avoid flour and powdered substances as they can remain airborne and cross contaminate surfaces up to 3 days after
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LifeStyle continued. Travel considerations Plan ahead, bring food along, web search/call ahead Travel abroad, gluten free standards may be different
Slide 32-

Patient Resources Several National organizations National Celiac Association (NCA) www.nationalceliac.org Celiac Disease Foundation (CDF) www.celiac.org Gluten Intolerance Group (GIG) www.gluten.net National Foundation for Celiac Awareness (NFCA) beyondceliac.org American Celiac Disease Alliance www.americanceliac.org
Slide 33-

What’s on the Horizon? Testing and Diagnosis ImmusanT biotechnology company in Norway has developed a test to identify T cell response characteristics to identify celiac disease looking specifically at the HLA DQ2 gene marker for celiac disease. (HLA DQ-gluten tetrameter assay) 4 groups studied: 1. CD on GF diet 2. CD not on GF diet 3. CD ruled out but following GF diet 4. Control group no CD; not on GF diet tTg IgA Ab predicted 9 of 10 pt’s not on a GF diet but only 4 of 10 pt’s following a gf diet New test is 95% accurate dx in diagnosing CD while on GF diet
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Horizon… (Pre-Clinical) Treatments… Pre-Clinical phase Amyra Biotech Ag Swiss company developing an enzyme-based treatment targeted to inhibit toxic potential of gluten Avaxia Biologics Research focus on inflammatory GI conditions. Identified inflammatory cytokine targets Abs, developing but not ready for trials yet
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Horizon… (Pre-Clinical) Calypso Biotech, CALY-002 An Ab that inhibits cytokine IL-15 for refractory celiac disease, not yet in phase 1 trials ExPharma Limited/Nemysis Limited Developing a compound to detoxify ingested gluten to treat symptoms of CD Intrexon Actobiotics Actobiotics deliver therapeutic molecules to GI and oral tracts to treat tissue injury
Slide 36-

Horizon… (Pre-Clinical) James Cook University/Hookworm Larvae May secrete anti-inflammatory proteins to restore gluten tolerance Provid Pharmaceuticals Developing gene inhibitors of DQ2 and DQ8 PvP Biologics, KumaMax Developing an enzyme to recognize/break down parts of gluten that trigger rxn, reduce symptoms/intestinal damage
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Horizon…(Pre-Clinical) Selecta Biosciences and Sanofi, SVP Synthetic vaccine particle to develop immunotherapy Sitari Pharma Developing Tx that target Transglutaminase 2 enzyme inhibitors to minimize immune response TEC Edmonton/Univ of Alberta Immune powered eggs through targeted egg yolk Abs
Slide 38-

Horizon VU-Amsterdam An-PEP Aspergillus niger prolyl endoprotease to lessen effects of gluten Phase 1 Cour Pharmaceuticals, TIMP-GLIA New drug that reprograms immune system to tolerate gluten as non-threatening substance, immunosuppressive
Slide 39-

Phase 1 ZED 1227 First direct acting transglutaminase inhibitor completed phase 1b trial. Next is phase 2a clinical trial Glenmark, GBR 830 Antibody targets activated T cells. Phase 1 studies well tolerated, transitioning to phase 2
Slide 40-

Phase 2 Celimmune, AMG 714 Antibody that targets IL-15 cytokine. Phase 2 study for diet non-responsive CD, and SB T-cell lymphoma ImmunogenX, IMGX003 (ALV003) Mix of 2 gluten specific enzymes to break down gluten proteins into small harmless fragments. Extensive phase 1 and 2 trials-only treatment to date that lessens injury and improves symptoms
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Phase 2 Innovate Biopharmaceuticals, INN-202 (Larazotide Acetate) derived from cholera toxin Tight junction regulator to restore “leaky” or open junctions to normal state. Reduce inflammatory process in response to gluten. Phase 2b in GFD non-responders underway
Slide 42-

Phase 2 ImmusanT, Nexvax 2 Disease modifying treatment; Reprograms T-cells so inflammatory response to gluten isn’t triggered. Specific to DQ2 gene present in 80-90% of CD. Potential to return to a normal diet For inadvertent gluten exposure and also Booster shots to establish long-term tolerance
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References