Celiac Disease

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11 Year Old Female with Epistaxis. 11 year old female developed right knee pain, swelling, and limp 2 days prior to admission.Plain radiographs revealed knee effusion.Later that evening she developed persistent nose bleeds, ultimately requiring cauterization.Initial laboratory data revealed PT

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Celiac Disease

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1. Celiac Disease Michael Kappelman, MD, MPH University of North Carolina at Chapel Hill Nov 9, 2010

2. 11 Year Old Female with Epistaxis 11 year old female developed right knee pain, swelling, and limp 2 days prior to admission. Plain radiographs revealed knee effusion. Later that evening she developed persistent nose bleeds, ultimately requiring cauterization. Initial laboratory data revealed PT>60, INR>23, PTT=98, and HCT=27.

3. 11 Year Old Female with Epistaxis PMH: Trisomy 21: Duodenal atresia repair as infant Tetrology of Fallot repair as infant Mild Asthma Medications: None (no recent antibiotics) Allergy: None Immunizations: UTD

4. 11 Year Old Female with Epistaxis Family History: No bleeding or clotting disorders. No GI or liver disease. Maternal grandmother with hypothyroidsim. No other FH of autoimmunity. Social History: Noncontributory Review of Systems: No fever or weight loss. Normal diet (? Limited vegetables). No adenopathy. No N/V/D/abd pain. No extraintestinal manifestations of IBD.

5. 11 Year Old Female with Epistaxis Physical Examination: Ht: 107cm (<3%) Wt: 20.6 kg (<3%) BMI: 18 (57%) General: Developmentally delayed. No acute distress. HEENT: Prominent Down’s features Neck: Supple, no goiter, no adenopathy Cardiac: 3/6 murmur, no evidence of CHF Chest: Clear to auscultation Abdomen: Soft, nontender, nondistended, no HSM Extremity: No C/C/E Skin: No rash, petechiae, bruising

6. 11 Year Old Female with Epistaxis Initial Laboratory Data: WBC: 7.1, HCT 28.1, Plt 409 (Normal WBC differential and RBC indices) PT=22.4 INR=3.3 PTT= 41.6 Na 139, K 4.2, Cl 104, HCO3 30.6, Bun 18, Cr 0.4, Glu 96, Ca 7.2, iCa 1.14, Phos 3.3, Mg 1.4 SGPT 52, SGOT 48, bili 0.6/0.2, Alk Phos 48, Alb 1.3 U/A: 1.014, PH 5.5, No RBC/WBC, no protein

7. 11 Year Old Female with Epistaxis Follow-up Laboratory Data: PT mixing study: consistent with factor deficiency PTT mixing study consistent with factor deficiency Factor Value Reference range II 7 60-140 V 117 60-140 VII 27 60-140 VIII 184 50-200 IX 10 60-140 X 3 60-140 XI 66 60-140 XII 57 60-140

8. 11 Year Old Female with Epistaxis Follow-up Laboratory Data: Vitamin Value Reference range Alpha tocopherol 3.7 5.7-19.9 Beta gamma tocopherol 0.4 0.0-4.3 25 OH Vitamin D 3.7 8.9-46.7 Vitamin A 15 26-49

9. 11 Year Old Female with Epistaxis Malabsorbtive Testing: Stool Elastase: 799 Celiac Serologies: Tissue Transglutaminase IgA >175 Anti Endomysial Antibody 1:1280 IgA 72

10. 11 Year Old Female with Epistaxis

11. 11 Year Old Female with Epistaxis Patient follow-up: She received 3 doses of subcutaneous vitamin K. PT=11.9 INR=0.9 PTT=22.5 Started on gluten free diet. Six months later, coagulopathy and hypoalbuminemia resolved

12. 12 Celiac Definition Celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. Occurs in genetically susceptible individuals DQ2 and/or DQ8 positive HLA haplotype is necessary but not sufficient A unique autoimmune disorder because: Both the environmental trigger (gluten) and the autoantigen (tissue Transglutaminase) are known Elimination of the environmental trigger leads to a complete resolution of the disease

13. 13 Epidemiology The “old” Celiac Disease Epidemiology:

14. 14 Celiac Disease in London, Year 1938

15. 15 The Changing Celiac Epidemiology

16. 16 Celiac Disease Epidemiological Study in USA

17. 17 Celiac Disease Prevalence Data

18. 18 The Celiac Iceberg

19. 19 High risk populations The prevalence of Celiac Disease is higher in patients who have the following: Certain genetic disorders or syndromes (5-10%) Williams syndrome, Turner syndrome, Trisomy 21 Other autoimmune conditions (5%) Type 1 DM, Thyroiditis IgA deficiency Relative of a biopsy-proven celiac (5%)

20. 20 Clinical Manifestations Gastrointestinal (“classical”) Non-gastrointestinal ( “atypical”) Asymptomatic

21. 21 Gastrointestinal Manifestations (“Classic”) Most common age of presentation: 6-24 months Chronic or recurrent diarrhea Abdominal distension Anorexia Failure to thrive or weight loss

22. 22 Typical Celiac Disease

23. 23 Non Gastrointestinal Manifestations/complications Dermatitis Herpetiformis Dental enamel hypoplasia Osteopenia/Osteoporosis Short Stature Delayed Puberty Recurrent stomatitis Fertility problems

24. 24 Dermatitis Herpetiformis Erythematous macule > urticarial papule > tense vesicles Severe pruritus Symmetric distribution 90% no GI symptoms 75% villous atrophy Gluten sensitive

25. 25 Dental Enamel Defects This slide demonstrates some of the subtle dental enamel defects that can be seen in a patient with celiac disease. The enamel defects occur in the secondary dentition, which is forming in the gums when a child begins to ingest gluten. The enamel defects are vertical lines which can be seen as notches or linear defects in the teeth in all four quadrants. These patients are at increased risk for caries in unusual locations. Sealants may be protective.This slide demonstrates some of the subtle dental enamel defects that can be seen in a patient with celiac disease. The enamel defects occur in the secondary dentition, which is forming in the gums when a child begins to ingest gluten. The enamel defects are vertical lines which can be seen as notches or linear defects in the teeth in all four quadrants. These patients are at increased risk for caries in unusual locations. Sealants may be protective.

26. 26 Osteoporosis Osteomalacia in a celiac patient showing pseudofractures of the pelvis (arrows). Patient was 45 years old and presented with bone pain and proximal muscle weakness (for over 2 years) in the absence of overt GI symptoms. Elevated alkaline phosphatase and absence of Vitamin D stores were seen. Osteomalacia in a celiac patient showing pseudofractures of the pelvis (arrows). Patient was 45 years old and presented with bone pain and proximal muscle weakness (for over 2 years) in the absence of overt GI symptoms. Elevated alkaline phosphatase and absence of Vitamin D stores were seen.

27. 27 Short Stature/Delayed Puberty Short stature in children / teens: ? ~10% of short children and teens have evidence of celiac disease Delayed menarche: ? Higher prevalence in teens with untreated Celiac Disease

28. 28 Recurrent Aphtous Stomatitis

29. 29 Fe-Deficient Anemia Resistant to Oral Fe 5-8% of adults with unexplained iron deficiency anemia have Celiac Disease In children with newly diagnosed Celiac Disease: ? Anemia is common ? Little evidence that Celiac Disease is common in children presenting with anemia

30. 30 Hepatitis Up to 9% of adults with elevated ALT, AST have silent Celiac Disease ? Liver biopsies in these patients showed non- specific reactive hepatitis ? Liver enzymes normalized on gluten-free diet Similar in children

31. 31 CT Scan Showing Occipital Calcifications in a Boy with Celiac Disease and Epilepsy

32. 32 Arthritis and Neurological Problems Arthritis in adults Fairly common, including those on gluten-free diets Juvenile chronic arthritis Up to 3% have Celiac Disease Neurological problems Epilepsy with cranial calcifications in adults Evidence for this condition in children with Celiac Disease is not as strong

33. 33 Celiac Disease Complicated by Enteropathy-Associated T-cell Lymphoma (EATL)

34. 34 Silent: No or minimal symptoms, “damaged” mucosa and positive serology Identified by screening asymptomatic individuals from groups at risk such: First degree relatives, Type 1 DM, Trisomy 21, etc. Asymptomatic patients are still at risk of osteopenia/osteoporosis and other complications Treatment with a gluten-free diet is recommended for asymptomatic children with intestinal changes Asymptomatic

35. 35

36. 36 Pathogenesis Genetic predisposition Environmental triggers Dietary Non dietary?

37. 37 Several genes are involved The most consistent genetic component depends on the presence of HLA-DQ (DQ2 and / or DQ8) genes Other genes (not yet identified) account for 60 % of the inherited component of the disease HLA-DQ2 and / or DQ8 genes are necessary (No DQ2/8, no Celiac Disease!) but not sufficient for the development of the disease Genetics

38. 38 Dietary Factors

39. 39 Dietary Factors

40. 40 Dietary Factors Though not “glutens”, rye and barley have similar epitopes and can trigger disease Role of oats is questionable.

41. 41 Tissue Transglutaminase (TTG) Normal gut enzyme released during injury and stabilizes the cross-linking of proteins in granulation tissue Role in Celiac Disease Modification of gliadin epitopes Autoantibodies against TTG correlate with active Celiac Disease - ? involved in pathogenesis

42. 42 Diagnostic testing: Serology HLA Testing Endoscopy and duodenal biopsy Diagnosis A diagnosis of celiac disease means the individual must stay on a strict gluten free diet for life. Following such a diet strictly is not always easy as there are many hidden sources of "gluten". A gluten free diet may also involve added cost to the individual and impact their quality of life. Therefore it is essential that the physician first confirm the diagnosis before recommending life long adherence to the diet. On the other hand it is equally important to not miss the diagnosis of celiac disease. Failure to treat an individual with celiac disease carries potential adverse long term health consequences involving both increased morbidity and mortality. A diagnosis of celiac disease means the individual must stay on a strict gluten free diet for life. Following such a diet strictly is not always easy as there are many hidden sources of "gluten". A gluten free diet may also involve added cost to the individual and impact their quality of life. Therefore it is essential that the physician first confirm the diagnosis before recommending life long adherence to the diet. On the other hand it is equally important to not miss the diagnosis of celiac disease. Failure to treat an individual with celiac disease carries potential adverse long term health consequences involving both increased morbidity and mortality.

43. 43 Serological Tests Role of serological tests: Identify symptomatic individuals who need a biopsy Screening of asymptomatic “at risk” individuals Supportive evidence for the diagnosis Monitoring dietary compliance Serological tests for celiac disease have a number of potential uses. First, they may be used to identify symptomatic individuals who require an intestinal biopsy to diagnose celiac disease. This is particularly useful in those with non specific gastrointestinal complaints or with non gastrointestinal symptoms of celiac disease. Second, the tests are helpful for screening asymptomatic individuals who belong to a group considered at increased risk for celiac disease. Those with positive tests should be referred for a biopsy. Third, positive tests prior to treatment, that become negative on treatment, in an individual with characteristic changes on small intestinal biopsy are strong supportive evidence for the diagnosis of celiac disease. Fourth, tests that revert from positive to negative may provide indirect evidence that the individual is adhering to the diet. Alternatively, tests that become positive again after having become negative suggest the individual is again ingesting gluten containing products. Serological tests for celiac disease have a number of potential uses. First, they may be used to identify symptomatic individuals who require an intestinal biopsy to diagnose celiac disease. This is particularly useful in those with non specific gastrointestinal complaints or with non gastrointestinal symptoms of celiac disease. Second, the tests are helpful for screening asymptomatic individuals who belong to a group considered at increased risk for celiac disease. Those with positive tests should be referred for a biopsy. Third, positive tests prior to treatment, that become negative on treatment, in an individual with characteristic changes on small intestinal biopsy are strong supportive evidence for the diagnosis of celiac disease. Fourth, tests that revert from positive to negative may provide indirect evidence that the individual is adhering to the diet. Alternatively, tests that become positive again after having become negative suggest the individual is again ingesting gluten containing products.

44. 44 Serological Tests Antigliadin antibodies (AGA) Antiendomysial antibodies (EMA) Anti tissue transglutaminase antibodies (TTG) Commercially available tests for celiac disease include the antigliadin, anti endomysial and anti tissue-transglutaminase tests. Tissue transglutaminase has been identified as the auto-antigen in celiac disease against which endomysial antibodies are directed. Initial transglutaminase tests used guinea pig protein as the antigen. Cloning of the gene for human transglutaminase has allowed for tests using human recombinant protein. In addition to antibody tests, some commercial laboratories are offering tests to identify the HLA DQ2 and DQ8 genotypes that are known to be strongly associated with celiac disease.   Commercially available tests for celiac disease include the antigliadin, anti endomysial and anti tissue-transglutaminase tests. Tissue transglutaminase has been identified as the auto-antigen in celiac disease against which endomysial antibodies are directed. Initial transglutaminase tests used guinea pig protein as the antigen. Cloning of the gene for human transglutaminase has allowed for tests using human recombinant protein. In addition to antibody tests, some commercial laboratories are offering tests to identify the HLA DQ2 and DQ8 genotypes that are known to be strongly associated with celiac disease.  

45. 45 Antigliadin Antibodies Antibodies (IgG and IgA) to the gluten protein in wheat, rye and barley Advantages relatively cheap & easy to perform Disadvantages poor sensitivity and specificity Antigliadin antibodies were the earliest tests developed for use in celiac disease. They are directed against the gliadin fraction of the gluten protein found in wheat. Both an IgA and an IgG based antibody are available. The advantages of the antigliadin tests are that they are relatively cheap and easy to perform. The major disadvantage is that they are relatively poorly sensitive and specific. Antigliadin antibodies were the earliest tests developed for use in celiac disease. They are directed against the gliadin fraction of the gluten protein found in wheat. Both an IgA and an IgG based antibody are available. The advantages of the antigliadin tests are that they are relatively cheap and easy to perform. The major disadvantage is that they are relatively poorly sensitive and specific.

46. 46 Endomysial Antibody - EMA IgA based antibody against reticulin connective tissue around smooth muscle fibers Advantages high sensitivity and specificity Disadvantages false negative in young children operator dependent expensive & time consuming false negative in IgA deficiency Endomysial antibodies are IgA based and directed against the reticulin connective tissue around smooth muscle fibers. The test is performed by means of an indirect immunofluorescent assay using monkey esophagus or human umbilical cord as substrate. Either substrate is equally effective. The advantage of this test is that it is highly sensitive and specific. The disadvantages include the fact that it is operator dependent and hence potentially prone to errors in interpretation, it is generally more time consuming to perform and thus more expensive and it does not allow detection of celiac disease in individuals with selective IgA deficiency. Endomysial antibodies are IgA based and directed against the reticulin connective tissue around smooth muscle fibers. The test is performed by means of an indirect immunofluorescent assay using monkey esophagus or human umbilical cord as substrate. Either substrate is equally effective. The advantage of this test is that it is highly sensitive and specific. The disadvantages include the fact that it is operator dependent and hence potentially prone to errors in interpretation, it is generally more time consuming to perform and thus more expensive and it does not allow detection of celiac disease in individuals with selective IgA deficiency.

47. 47 Tissue Transglutaminase - TTG IgA based antibody against tissue transglutaminase (Celiac Disease autoantigen) Advantages high sensitivity and specificity (human TTG) non operator dependent (ELISA/RIA) relatively cheap Disadvantages false negative in young children false negative in IgA deficiency possibly less specific than EMA The tissue transglutaminase test is IgA based and performed by means of either an ELISA or RIA technique. The major advantages of the test are that it is highly sensitive and specific, is non operator dependent and is relatively cheap to perform. The disadvantages are that it is unable to detect celiac disease in IgA deficient individuals and it may be less specific than the endomysial antibody. The tissue transglutaminase test is IgA based and performed by means of either an ELISA or RIA technique. The major advantages of the test are that it is highly sensitive and specific, is non operator dependent and is relatively cheap to perform. The disadvantages are that it is unable to detect celiac disease in IgA deficient individuals and it may be less specific than the endomysial antibody.

48. 48 The sensitivities and specificities for the various tests are again depicted in a graphic format. The sensitivities and specificities for the various tests are again depicted in a graphic format.

49. 49 Serum IgA Level Individuals with IgA deficiency are at increased risk for Celiac Disease IgA deficient individuals will have negative EMA-IgA & TTG-IgA Check IgA levels with Celiac Disease serology in all symptomatic individuals Consider IgG based tests (EMA-IgG & TTG-IgG) in IgA deficiency It is known that individuals with selective IgA deficiency are at increased risk for celiac disease. This presents a problem when using serological tests for screening purposes as most tests are based upon an IgA antibody and hence will give a negative result. In order to better interpret the relevance of a negative endomysial or transglutaminase test in a symptomatic individual, determination of a serum IgA level is helpful. In the event the individual has a low serum IgA level indicative of IgA deficiency, the IgA based endomysial and transglutaminase tests will fail to identify those who have celiac disease. In such cases additional strategies are needed. One such strategy is to use IgG based anti-endomysial and anti-tissue transglutaminase tests that are offered by some commercial laboratories. Studies suggest these are not as sensitive or specific as the IgA based tests but are superior to the IgG based anti-gliadin tests. If the clinical suspicion for celiac disease is strong, it may be necessary to proceed to an intestinal biopsy even if all serological tests for celiac disease are negative. It is known that individuals with selective IgA deficiency are at increased risk for celiac disease. This presents a problem when using serological tests for screening purposes as most tests are based upon an IgA antibody and hence will give a negative result. In order to better interpret the relevance of a negative endomysial or transglutaminase test in a symptomatic individual, determination of a serum IgA level is helpful. In the event the individual has a low serum IgA level indicative of IgA deficiency, the IgA based endomysial and transglutaminase tests will fail to identify those who have celiac disease. In such cases additional strategies are needed. One such strategy is to use IgG based anti-endomysial and anti-tissue transglutaminase tests that are offered by some commercial laboratories. Studies suggest these are not as sensitive or specific as the IgA based tests but are superior to the IgG based anti-gliadin tests. If the clinical suspicion for celiac disease is strong, it may be necessary to proceed to an intestinal biopsy even if all serological tests for celiac disease are negative.

50. 50 HLA Tests HLA alleles associated with Celiac Disease DQ2 found in 95% of celiac patients DQ8 found in remaining patients DQ2 found in ~30% of general population Value of HLA testing High negative predictive value Negativity for DQ2/DQ8 excludes diagnosis of Celiac Disease with 99% confidence The role of HLA testing in celiac disease needs to be addressed. It is known that over 95% of all individuals with celiac disease are HLA DQ2 positive and virtually all the rest are positive for the HLA DQ8 genotype. However, about 30% of the general population is also HLA DQ2 positive. Thus, while these tests will likely demonstrate a high degree of sensitivity for celiac disease, they will be poorly specific. In contrast, knowing an individual is neither HLA DQ2 nor DQ8 positive may be helpful to the clinician as this almost completely eliminates the possibility the individual has celiac disease. The role of HLA testing in celiac disease needs to be addressed. It is known that over 95% of all individuals with celiac disease are HLA DQ2 positive and virtually all the rest are positive for the HLA DQ8 genotype. However, about 30% of the general population is also HLA DQ2 positive. Thus, while these tests will likely demonstrate a high degree of sensitivity for celiac disease, they will be poorly specific. In contrast, knowing an individual is neither HLA DQ2 nor DQ8 positive may be helpful to the clinician as this almost completely eliminates the possibility the individual has celiac disease.

51. 51 HLA Tests Potential role for DQ2/DQ8 asymptomatic relatives Down, Turner & Williams syndrome type 1 diabetes diagnostic dilemmas Determining the HLA type may be of benefit in some asymptomatic individuals with negative serological antibody tests who belong to a group considered at increased risk for celiac disease. These include individuals who are relatives of a confirmed case of celiac disease and those with Down syndrome, Turner syndrome or William syndrome and type 1 diabetes. It is known that some such individuals with initial negative serological tests will subsequently become positive and have biopsy changes compatible with celiac disease over a period of time if testing is repeated at intervals. Knowing an individual belonging to one of these groups was negative for both HLA DQ2 and DQ8 enables the physician to reassure them there is no further need to test them for celiac disease. HLA typing for the celiac disease haplotypes may also help in some cases where the diagnosis is not clear, either because the individual never had a biopsy prior to starting treatment or because the histological features are not difficult to interpret. Once again, in these cases the absence of either of the HLA types virtually eliminates the likelihood of celiac disease in the individual. Determining the HLA type may be of benefit in some asymptomatic individuals with negative serological antibody tests who belong to a group considered at increased risk for celiac disease. These include individuals who are relatives of a confirmed case of celiac disease and those with Down syndrome, Turner syndrome or William syndrome and type 1 diabetes. It is known that some such individuals with initial negative serological tests will subsequently become positive and have biopsy changes compatible with celiac disease over a period of time if testing is repeated at intervals. Knowing an individual belonging to one of these groups was negative for both HLA DQ2 and DQ8 enables the physician to reassure them there is no further need to test them for celiac disease. HLA typing for the celiac disease haplotypes may also help in some cases where the diagnosis is not clear, either because the individual never had a biopsy prior to starting treatment or because the histological features are not difficult to interpret. Once again, in these cases the absence of either of the HLA types virtually eliminates the likelihood of celiac disease in the individual.

52. 52 Endoscopic Findings A small intestinal biopsy and histological evaluation for the characteristic changes of celiac disease remains an essential component for confirming the diagnosis. Most biopsies today are obtained by means of an upper GI endoscopy with intubation of the duodenum. There are some macroscopical that are suggestive of celiac disease including a scalloped appearance along the duodenal folds and mucosal nodularity as shown in this slide. However, these findings are by no means reliable and mucosal biopsies are always needed. A small intestinal biopsy and histological evaluation for the characteristic changes of celiac disease remains an essential component for confirming the diagnosis. Most biopsies today are obtained by means of an upper GI endoscopy with intubation of the duodenum. There are some macroscopical that are suggestive of celiac disease including a scalloped appearance along the duodenal folds and mucosal nodularity as shown in this slide. However, these findings are by no means reliable and mucosal biopsies are always needed.

53. Histology

54. Need for biopsy in symptomatic patients with + serology As of 2010, guidelines endorse duodenal bx Establishment of definitive diagnosis Exclude other etiologies which may have similar symptoms, given that celiac is often asymptomatic

55. Establish Definitive Diagnosis Lifelong disease which requires strict adherence to GFD (difficult, costly) Impacts future insurability (health, life, disability) Significant long-term prognosis (complications, mortality) Serology not 100% specific (PPV affected by pre-test probability) Risk of procedure small Histology affected by gluten free diet: 1 chance for pre-diet confirmation Brief delay in diet initiation while awaiting scope of little consequence in long-term, chronic disease

56. Alternative to EGD Resolution of symptoms and normalization of antibodies may also be used to confirm diagnosis Symptoms hard to follow due to common co-morbid GI illness (IBS, lactose) Serologic response contingent on dietary adherence 6 months in to GFD not an ideal time question diagnosis

57. 57 Treatment Only treatment for celiac disease is a gluten-free diet (GFD) Strict, lifelong diet Avoid: Wheat Rye Barley

58. 58 Follow-up Periodic serological assessment (may take 6 months to normalize) Monitoring of growth velocity, weight, pubertal development Monitoring of anemia, vit D, other nutritional deficiencies Education Adherence

59. 59 Barriers to Compliance Ability to manage emotions – depression, anxiety Ability to resist temptation Feelings of deprivation Time pressure – time to plan, prepare food is longer Assessing gluten content in foods/label reading Eating out –difficult to ensure food is safe Social Events – Not wanting to look/be different J. Am. Diet. Assoc. (1994) 94(8): 874-876. This list of obstacles was adapted from a list generated by people with diabetes. The practical, social and emotional impact of a celiac diagnosis is an ever present reality for a person with the condition. No longer able to take the convenience, availability or content of food for granted, a celiac must remain armed with the knowledge of a food scientist, the savvy of a world class chef schooled in all aspects of food preparation, and the ability to anticipate and prepare for the need to bring along gluten-free alternatives for events, meetings, and dinners out. Underlying these practical matters are fears and feelings which impact health behavior. While it is normal to feel angry and overwhelmed at times, medical professionals need to monitor patients who may not be adjusting to the diagnosis as well as could be expected. Depression, anxiety, anger and fear that interfere with daily activities or lead to behaviors like removing more foods than are necessary from the diet requires additional intervention. J. Am. Diet. Assoc. (1994) 94(8): 874-876. This list of obstacles was adapted from a list generated by people with diabetes.

60. 60 Factors that Improve Adherence Knowledge about the gluten-free diet Understanding of serious complications that can occur to the patient Ability to break down big changes into smaller steps Positive coping skills Ability to recognize and manage mental health issues Trust in physicians and dietitians Regular follow-up, motivational interviewing, serological assessment What you can do: State information about the disease and the patients tests in an objective manner. (Avoid guilt, pressure) Provide a prompt referral to a knowledgeable dietitian as soon as possible after diagnosis and provide information that will help reinforce or shape the patient’s knowledge about their condition. (Physician credibility reinforces internal knowledge) Help patients learn positive coping skills by breaking down big changes into smaller steps. (recommend positive strategies) Intervene when depression or anxiety is apparent; research shows that the successful management of these conditions are crucial for adherence and adopting positive health behaviors. Reinforce internally motivated factors that are apparent in patient’s life (a patient who feels better is experiencing an internal factor). What you can do: State information about the disease and the patients tests in an objective manner. (Avoid guilt, pressure) Provide a prompt referral to a knowledgeable dietitian as soon as possible after diagnosis and provide information that will help reinforce or shape the patient’s knowledge about their condition. (Physician credibility reinforces internal knowledge) Help patients learn positive coping skills by breaking down big changes into smaller steps. (recommend positive strategies) Intervene when depression or anxiety is apparent; research shows that the successful management of these conditions are crucial for adherence and adopting positive health behaviors. Reinforce internally motivated factors that are apparent in patient’s life (a patient who feels better is experiencing an internal factor).

61. 61 Gluten-Containing Grains to Avoid Wheat Bulgar Filler Wheat Bran Couscous Graham flour Wheat Starch Durum Kamut Wheat Germ Einkorn Matzo Flour/Meal Barley Emmer Semolina Barley Malt/ Extract Faro Spelt Rye Triticale

62. 62 Sources of Gluten OBVIOUS SOURCES Bread Bagels Cakes Cereal Cookies Pasta / noodles Pastries / pies Rolls

63. 63 Sources of Gluten

64. 64 Ingredients to Question (may contain gluten) Seasonings and spice blends or mixes Modified food starch Malt/ malt extract/ flavoring Modified hop extract and yeast-malt sprout extract Dextrin Caramel color

65. 65 Gluten-Free Grains and Starches

66. 66 Safe Ingredients

67. 67 Other Items to Consider Lipstick/Gloss/Balms Mouthwash/Toothpaste Play Dough Stamp and Envelope Glues Vitamin, Herbal, and Mineral preparations Prescription or OTC Medications

68. 68 Potential Nutritional Complications in Untreated Celiac Disease

69. 69 Potential Nutritional Complications in Untreated Celiac Disease

70. 70 Anemia in Celiac Disease Microcytic anemia - iron absorption most efficient in the duodenum Megaloblastic/Macrocytic anemia – folate is absorbed primarily in the proximal third of the small intestine (location of folate hydrolases) Vitamin B-12 deficiency occurs rarely

71. 71 Importance of Folic Acid Supplementation Folate hydrolases are needed in the brush border for absorption Best absorbed in proximal 3rd of duodenum. Increased use of folate in apoptosis Low folate impairs cell division

72. 72 Importance of Folic Acid Supplementation Low folate increases irritability & forgetfulness Celiac Disease increases risk of GI malignancies Folate supplement may have anti-cancer effect as needed for DNA replication Supplement Celiac Disease patients with 1 mg folic acid

73. 73 Calcium and Vitamin D Requirements 800 to 1200 mg/day of Calcium for low bone mineral density (LBMD) in males 1200-1500 mg/day of Calcium for treatment of LBMD in females 400 IU of Vitamin D daily Up to 2/3 of patients on a gluten-free diet have suboptimal calcium intake

74. 74 Eating Healthy on the Gluten-Free Diet Similar to a normal diet Moderate cholesterol Moderate protein Low fat, sodium, alcohol, and concentrated sugars High fiber Variety of foods for good nutrient balance A balanced GFD resembles a healthy diet for anyone, with the exception that GF starches are substituted for gluten-containing products. Including a variety of foods in the diet by using many fruits and vegetables, dairy foods and grains, helps to round out the nutrients in the diet. Gluten-free grains, starches, and flours tend to be denser than their gluten-containing counterparts. A gluten-free bread product may have 1˝ to 2 times the calories than a comparable wheat product. Patients should be educated about re-feeding and appropriate serving sizes to avoid possible excess calorie intake and weight gain. Label-reading becomes important to helping the patient become aware of the calorie content of gluten-free products. The lack of enrichment of GF products, may mean the need to supplement the diet with vitamins and minerals. A balanced GFD resembles a healthy diet for anyone, with the exception that GF starches are substituted for gluten-containing products. Including a variety of foods in the diet by using many fruits and vegetables, dairy foods and grains, helps to round out the nutrients in the diet. Gluten-free grains, starches, and flours tend to be denser than their gluten-containing counterparts. A gluten-free bread product may have 1˝ to 2 times the calories than a comparable wheat product. Patients should be educated about re-feeding and appropriate serving sizes to avoid possible excess calorie intake and weight gain. Label-reading becomes important to helping the patient become aware of the calorie content of gluten-free products. The lack of enrichment of GF products, may mean the need to supplement the diet with vitamins and minerals.

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