16 Saturday General Session Celiac Disease and Gluten Free Diets Harry J. Thomas, MD Gastroenterologist Austin Gastroenterology Austin, Texas Educational Objectives By completing this educational activity, the participant should be better able to: 1. Discuss symptoms and risk factors associated with celiac disease, including possible comorbidities. 2. Perform an examination to identify the physical symptoms of celiac disease and recommend laboratory testing and intestinal biopsies as necessary. 3. Educate patients on strategies and a gluten-free diet plan to treat and manage the symptoms of celiac disease. 4. Differentiate specific issues, disease processes, and treatments based on ethnicity, gender and genetics. Speaker Disclosure Dr. Thomas has disclosed that he has no actual or potential conflict of interest in relation to this topic.
Transcript
16
Saturday General Session
CeliacDiseaseandGlutenFreeDiets
HarryJ.Thomas,MDGastroenterologist Austin Gastroenterology Austin, Texas EducationalObjectivesBy completing this educational activity, the participant should be better able to:
1. Discuss symptoms and risk factors associated with celiac disease, including possible comorbidities.
2. Perform an examination to identify the physical symptoms of celiac disease and recommend laboratory testing and intestinal biopsies as necessary.
3. Educate patients on strategies and a gluten-free diet plan to treat and manage the symptoms of celiac disease.
4. Differentiate specific issues, disease processes, and treatments based on ethnicity, gender and genetics.
SpeakerDisclosure Dr. Thomas has disclosed that he has no actual or potential conflict of interest in relation to this topic.
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Celiac Disease Diagnosis and Management
Harry J. Thomas, MD
Texas Academy of Family Physicians
2019 C. Frank Webber Lectureship
Speaker Disclosure
• Dr. Thomas has disclosed that he has no actual or potential conflict of interest in relation to this topic.
Educational Objectives
By completing this educational activity, the participant should be better able to:
1. Discuss symptoms and risk factors associated with celiac disease, including possible comorbidities.
2. Perform an examination to identify the physical symptoms of celiac disease and recommend laboratory testing and intestinal biopsies as necessary.
3. Educate patients on strategies and a gluten-free diet plan to treat and manage the symptoms of celiac disease.
4. Differentiate specific issues, disease processes, and treatments based on ethnicity, gender and genetics.
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Audience Polling Questions
Audience Polling 1
The USPSTF recommends screening for celiac disease in asymptomatic persons.
1. True
2. False
Audience Polling #2
Which of the following conditions is NOT associated with celiac disease?
1. Type 1 diabetes
2. Autoimmune thyroiditis
3. Down Syndrome
4. Cystic fibrosis
5. Selective IgA deficiency
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Audience Polling #3
Which of the following is the preferred initial screening test for celiac disease?
1. IgA anti-gliadin antibodies
2. IgA anti-endomysial antibodies
3. IgA anti–tissue transglutaminase antibodies
4. IgG anti–tissue transglutaminase antibodies
5. Testing for HLA-DQ2 and HLA-DQ8
Audience Polling #4
Patients with celiac disease have an increased risk of malignancy and mortality
1. True
2. False
Outline
• Definition
• History
• Epidemiology
• Clinical features
• Diagnosis
• Treatment
Gluten Related Disorders
• Celiac disease – An immune-mediated systemic disorder triggered by gluten and related prolamins present in wheat, barley, and rye that occur in genetically susceptible individuals who have the human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 haplotypes.
• Gluten sensitivity (non-celiac) – Clinical response to a GFD in the absence of serologic or histologic evidence of CD
• Wheat allergy – IgE mediated food allergy to wheat (0.2-1% of children)
Diagram of Immune Reaction to Wheat
Cianferoni A. Wheat allergy: diagnosis and management. J Asthma Allergy. 2016 Jan 29;9:13-25.
History
• Ancient disease described by Arataeus the Cappadocian. 2nd Century AD
• Described weight loss malabsorption “The Coeliac Affection.” Named it “koiliakos” after the Greek word “koelia” (abdomen).
• “If the stomach be irretentive of the food and if it pass through undigested and crude, and nothing ascends into the body, we call such persons coeliacs.”
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“Modern Times”
• Samuel Gee, physician to St. Bartholomew's Hospital and The Hospital for Sick Children, Great Ormond Street, London.
• In a lecture in 1887, Gee described a syndrome he termed the coeliac affection.
1924: Sidney Haas recommended the banana diet which was successful in treating 8 out of 10 children. The diet specifically excluded bread, crackers, potatoes and all cereals.
Modern Discovery
• The cause of the coeliac affection was unknown until the role of gluten was described by in 1950.
• 1940-1950: Willem Dicke, a Dutch pediatrician, noted an association between bread and cereal and relapsing diarrhea.
• WWII shortage of breads and cereals resulted in reduced symptoms in children.
• Empirical diet of pure fruit, potatoes, bananas, milk and meat.
• Symptoms re-occurred when bread was reintroduced after the war.
Diagnosis
• Small bowel biopsy 1950-1960 confirmed the gut as a target organ
• 1961 KB Taylor demonstrated the presence of antibodies to gliadin
Epidemiology
• The rate of diagnosis of celiac disease has substantially increased over the past 30 years
– In the United States, the prevalence of CD has increased 4-fold in the last 50 years
– Frequency is increasing in many developing countries, particularly in North Africa and the Middle East
– Low CD probability in individuals of Chinese, Japanese, or Sub-Saharan African descent
• Prevalence is 1.5-2 times as high among women as among men
Krigel A, Turner KO, et al. Ethnic Variations in Duodenal Villous Atrophy Consistent With Celiac Disease in the United States. Aug 2016, Volume 14, Issue 8,Pgs. 1105–1111
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HOW COMMON IS IT?
• 1% prevalence in general Western populations (possibly higher in Western Europe and Scandinavia)
• 3-6% prevalence in type 1 diabetes
• 5-10% prevalence in first degree relatives
• 10-15% prevalence in symptomatic iron deficiency anemia
• 3-6% prevalence in asymptomatic iron deficiency anemia*
• 1-3% prevalence in osteoporosis
* Pregnancy may unmask the effect of iron malabsorption, so testing pregnant women with moderate to severe anemia is worth while
Pathogenesis of Celiac Disease
EPITHELIUM
Innate response
LAMINA PROPRIA
Adaptive response
GENETIC FACTORS
GLUTEN
HLAHaplotype
HLA-DQ2 DQA1*0501/DQB1*0201 90% (one third of the general population)
HLA-DQ8 DQA1*0301/DQB1*0302 5%
At least one of the two genes encoding DQ2
DQB1*0201 or DQA1*0501 Almost all the remaining 5%
High NPV
Kagnoff MF. Celiac disease: pathogenesis of a model immunogenetic disease. J Clin Invest. 2007;117(1):41-49.
Outside the HLA
• DQ2 and DQ8 haplotypes are necessary but not sufficient for the development of CD
• At least 39 non-HLA genesthat confer a predisposition to the disease have been identified, most of which are involved in inflammatory and immune responses
Trynka G, et al. Fine points in mapping autoimmunity. Nature Genetics. Nov 28 (2011) Vol 43, Pgs 1173–1174 (2011)
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Established and Proposed Risk Factors for Celiac Disease
GlutenHLA DQ2/8Family history of celiac diseaseGI infections (rotavirus, Campylobacter, Reovirus)Summer season of birthAntibiotic useAcid suppression medicationLack of H. pylori colonizationComposition of gut microbiotaNorthern latitude (U.S.)Southern latitude (Sweden)
Conflicting StudiesMaternal iron supplementationElective Caesarian sectionBreast feedingAge at gluten introduction Amount of gluten consumedAvoiding cow’s milkIncome
Pathogenesis of Celiac Disease
EPITHELIUM
Innate response
LAMINA PROPRIA
Adaptive response
EPITHELIUM
Innate response
LAMINA PROPRIA
Adaptive response
GENETIC FACTORSGENETIC FACTORS
GLUTENGLUTEN
ENVIRONMENTAL FACTORS
ENVIRONMENTAL FACTORS
Choung RS, Murray J. The USPST Force Recommendation on Screening for Asymptomatic Celiac Disease: A Dearth of Evidence. JAMA. 2017;317(12):1221-1223.
DL Aventín, L Ilzarbe, JE Herrero-González. Recurrent Digital Petechiae and Weight Loss in a Young Adult. Gastro. June 2013; Vol 144, Issue 7, Pgs e10–e11
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of
screening for celiac disease in asymptomatic persons.
TESTING IS RECOMMENDED FOR CHILDREN WITH
• Diarrhea and failure to thrive
• Persistent GI symptoms including recurrent abdominal pain, anorexia, constipation and vomiting
• Dermatitis herpetiformis
• Dental enamel hypoplasia of permanent teeth
• Osteoporosis
• Short stature
• Delayed puberty
• Iron-deficient anemia resistant to oral iron
• Asymptomatic children with conditions associated with an increased prevalence of Celiac Disease
– Type 1 diabetes (3-16%)
– Autoimmune thyroiditis (5%)
– Down Syndrome (5%)
– Turner Syndrome (3%)
– Williams Syndrome
– Selective IgA deficiency
– First degree relatives of celiac patients (10-15%)
Celiac Diagnosis Serologic Tests
• Serologic screening recommended in all first-degree family members of patients who receive a diagnosis of CD.
• Serologic testing typically normalizes in celiac patients who are on a GFD. As a result, patients who have been consuming a GFD should be instructed to resume gluten-containing foods in order to reduce the risk of FN celiac Ab testing.
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Screen with tTG IgA (and Total IgA) Confirmatory Testing in CD
• Upper endoscopy with small-bowel biopsy
– Multiple biopsies of the duodenum (one or two biopsies of the bulb and at least four biopsies of the distal duodenum) are recommended to confirm the diagnosis of CD.
scalloping loss of duodenal folds
mosaic or nodular mucosa mucosal atrophy
Increased number of IELs (>25 per 100 enterocytes)
Elongation of the cryptsPartial to total villous atrophy
“Not all that Flattens is Sprue”
• Tropical sprue• Crohn’s disease• Bacterial overgrowth• Parasitic infections• HIV enteropathy• Whipple’s disease• Tuberculosis• Radiation enteritis• Intestinal lymphoma• Agammaglobulinemia• Common-variable immunodeficiency • Intolerance of foods other than gluten
MF Kagnoff. Celiac disease: pathogenesis of a model immunogenetic disease. J Clin Invest. 2007;117(1):41-49.
Prolamins gliadins secalins hordeins avenins
What about oats? Oats
• Majority of patients with CD can consume a moderate amount of pure oats (up to 70 g per day in adults) without side effects, but side effects do occur in some patients
The Gluten Threshold
• The lowest amount of daily gluten that causes damage to the celiac intestinal mucosa over time is 10-50 mg per day (a 25-g slice of bread contains approximately 1.6 g of gluten)
• Some patients can tolerate up to 5 g of gluten daily; others have intolerance after minimal exposure
Initial Management of Patients with Celiac Disease
• Referral to dietician and support group
• Repletion of nutritional deficiencies – Vitamins (A, D, E, B12), copper, zinc, carotene, folic acid, ferritin, iron, prothrombin time (PT)…thiamine, vitamin B6, magnesium, selenium
• Medication absorption – Incomplete absorption of medication in untreated, partially treated, or refractory CD (OCP)
• Prevention of bone loss – DXA (check PTH)
• Vaccination – Pneumococcal, meningococcal, flu
• Screening of first-degree relatives
Response to Treatment
• Approximately 70% of patients have noticeable clinical improvement within two weeks
• Symptoms improve faster than histology, especially when biopsies are obtained in the proximal intestine.
– The less severely damaged distal small intestine recovers faster than the proximal intestine, which is typically more severely affected due to relatively increased exposure to gluten
• Healing of the intestinal damage typically occurs within 6-24 months after initiation of the diet
Monitoring the Response to a Gluten-free Diet
• Serologic testing– Exclusion of gluten from the diet results in a gradual decline in
serum IgA antigliadin and IgA tTG levels (half-life of six to eight weeks).
– A normal baseline value is typically reached within 3 to 12 months depending upon the pre-treatment concentrations.
– Normal IgA tTG levels do not reliably indicate recovery from villous atrophy.
– Conversely, if the levels do not fall as anticipated, the patient is usually continuing to ingest gluten.
• High cost • Poor availability of gluten-free products (in developing countries) • Poor palatability • Absence of symptoms when dietary restrictions not observed • Inadequate information on gluten content of food or drugs • Inadequate dietary counseling • Inadequate initial information supplied by diagnosing physician • Inadequate medical or nutritional follow-up • Lack of participation in a support group • Inaccurate information from physicians, dietitians, support groups, or Internet • Dining out of the home • Social, cultural, or peer pressures • Transition to adolescence • Inadequate medical follow-up after childhood
Complications
Malabsorption
• Malnutrition (insufficient B vitamins, trace minerals on GFD)
• adenocarcinomas of the pharynx, esophagus, and small intestine
Pregnancy
• Infertility or recurrent abortion
• Fetal growth restriction
Neurologic disorders
Mortality Risk
Ludvigsson JF, Montgomery SM, Ekbom A, Brandt L, Granath F. Small-intestinal histopathology and mortality risk in celiac disease. JAMA. 2009 Sep 16;302(11):1171-8.
Celiac disease (Marsh stage 3)Inflammation (Marsh stage 1-2)Latent celiac disease - positive CD serology, normal mucosa (Marsh stage 0)
biopsies taken between 1969 and 2008 from all 28 pathology departments in Sweden3049 deaths among pts with CD, 2967 with inflammation, and 183 with latent CD
Cardiovascular disease and malignancy were the main causes of death in celiac disease.
Complications of Gluten-free Diet
• Women often experience breast tenderness for three months after starting a gluten-free diet
• GF foods often have less dietary fiber (constipation) and other micronutrients
• Cost more
• High arsenic, mercury levels
• T2D risk?
Nondietary Therapy for Celiac Disease
• AKA having their cake and eating it
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SE Crowe. Management of Celiac Disease: Beyond the Gluten-Free Diet. June 2014, Vol 146, Issue 7, Pgs 1594–1596.
Genetically modified wheat (RNAi/CRISPR to knock down/out the gliadin genes)
Prevention
• Rotavirus vaccination
• Probiotics?
Effect of Rotavirus Vaccination in Reducing Celiac Disease Autoimmunity in Susceptible Children
CGH 2017
Key Clinical Points
• CD is now known to affect persons of different ages, races, and ethnic groups, and it may be manifested without any GI symptoms.
• Measurement of IgA anti–tissue transglutaminase antibodies is the preferred initial screening test.
• The diagnosis is confirmed by means of upper endoscopy with duodenal biopsy.
• The cornerstone of treatment is the implementation of a strict gluten-free diet for life.
• Gluten sensitivity may occur in the absence of CD, and a definitive diagnosis should be made before implementing a lifelong gluten-free diet.
