Gastroenterology: Celiac Disease - PowerPoint Presentation

1. Gastroenterology: Celiac DiseaseCourses in Therapeutics and Disease State Management

2. Learning ObjectivesDiscuss the etiology and pathophysiology of celiac diseaseDescribe the gastrointestinal and extraintestinal symptoms of celiac diseaseDifferentiate between screening for and diagnosis of celiac diseaseExplain who should be screened for celiac diseaseDiscuss treatment of celiac disease including nonpharmacologic and lifestyle measures

3. Required ReadingPatel PN, Mangione RA. Celiac Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw-Hill; 2017 .

4. What is Celiac Disease?Celiac disease is a small intestinal immune-mediated enteropathy caused by intolerance to ingested glutenGluten is a generic term for a variety of proteins found in grains such as wheat, barley, and ryeLink: Table on grains and other foods that do and do not contain glutenChronic inflammation caused by exposure to gluten leads to GI discomfort, nutrient malabsorption, and systemic complicationsCeliac patients experience both GI and extraintestinal symptoms

5. EpidemiologyCeliac disease is common in North America and EuropeIt affects approximately 1% of AmericansThe prevalence of celiac disease is higher in women than men at rates ranging from 2:1 to 3:1It is estimated that only 10% - 15% of those with celiac disease in the U.S. have been diagnosed

6. Etiology (Slide 1 of 3)Celiac disease occurs when a genetically predisposed person ingests glutenWheat gluten proteins exist in 2 fractions: gliadins and gluteninsBarley contains proteins called hordeins and rye contains proteins called secalins both of which are similar to gluteninsIngestion of any of these proteins will lead to an autoimmune response in celiac disease patients

7. Etiology (Slide 2 of 3)Genetic factors likely play a role in the development of celiac disease A concordance rate of 85% in monozygotic twins has been reportedVirtually all patients with celiac disease have variants of HLA-DQ2 or HLA-DQ8 molecules that are expressed on the surface of antigen-presenting cells

8. Etiology (Slide 3 of 3)Certain infectious agents and other compounds may contribute to the development of celiac diseaseAdenovirus and hepatitis C viruses are thought to act as triggersCampylobacter jejuni, Giardia lamblia, rotavirus, and enterovirus infections have been described in case reports as associated with celiac diseaseInterferon-α has also been suggested to play a role in celiac disease development

9. Pathophysiology (Slide 1 of 2)Sensitive individual eats gluten  inappropriate T-lymphocyte response against the antigen in the small intestine  release of antibodies and activation of the inflammatory cascade (interferons, interleukins, TNF, etc.)  injury characterized by changes in the structure and loss of intestinal villi  malabsorption of vitamins, minerals, and essential nutrients

10. Pathophysiology (Slide 2 of 2)Link: Table on Proposed Pathophysiology of Celiac DiseaseLink: Figure showing small-intestinal mucosal biopsies

11. Signs and Symptoms (Slide 1 of 3)The recognition of celiac disease may be quite challenging due to the wide range of presenting symptoms, which includes patients who are asymptomaticClinical manifestations of celiac disease also vary between age groupsLink: Table on Selected Signs and Symptoms of Celiac Disease

12. Signs and Symptoms (Slide 2 of 3)Infants and young childrenGI: Diarrhea, abdominal distention, vomiting, anorexia, and sometimes constipationExtraintestinal: Failure to thrive, irritabilityOlder children and adolescentsGI: Diarrhea, abdominal distention, vomiting, anorexia, and sometimes constipationExtraintestinal: Short stature, delayed puberty, anemia, neurologic findings (peripheral neuropathy, ataxia, seizure, migraine, dementia)

13. Signs and Symptoms (Slide 3 of 3)AdultsGI: Classic presenting sign is diarrhea accompanied by abdominal pain or discomfortOther GI: Weight loss, constipationExtraintestinal: iron-deficiency anemia, osteoporosis, neurologic symptoms, dermatitis herpetiformis, hypoproteinemia, hypocalcemia, elevated liver enzymes

14. Dermatitis Herpetiformis (Slide 1 of 2)Dermatitis herpetiformis is a skin manifestation of small intestinal immune-mediated enteropathy caused by the ingestion of glutenIt is characterized by an extremely pruritic, bullous skin rash generally found on the elbows, knees, buttocks, and scalp but can occur anywhere on the bodyIt occurs in approximately 15% to 25% of those with celiac disease Can occur in patients of any age but most commonly is found in celiac disease patients between the ages of 30 to 40 years

15. Dermatitis Herpetiformis (Slide 2 of 2)Every patient with celiac disease does not develop dermatitis herpetiformis, but every person with dermatitis herpetiformis also has celiac diseaseLink: Photograph of dermatitis herpetiformis of the faceLink: Photograph of bullous dermatitis herpetiformis

16. Screening for Celiac Disease (Slide 1 of 3)Who should be screened for celiac disease?Children older than 3 and adults experiencing symptoms of celiac diseaseFirst-degree relatives of people with celiac diseaseParents, siblings, and children have a 1 in 10 risk compared to 1 in 100 in the general populationAny individual with an associated autoimmune disorder or other associated conditionExamples of these conditions include type 1 diabetes, autoimmune thyroid disease, rheumatoid arthritis, scleroderma, autoimmune liver disease, primary biliary cirrhosis, Down syndrome, Turner syndrome, Williams syndrome, Sjogren’s syndrome

17. Screening for Celiac Disease (Slide 2 of 3)Serologic tests screen for celiac disease antibodiesSerum IgA antibodies to tissue transglutaminase (tTG) are increased in most cases of active celiac diseaseThis test is referred to as a tTG-IgA test< 4.0 u/ml – Negative4 – 10 u/ml – Weak positive> 10 u/ml – PositiveThis test can be used to determine which patients should undergo a endoscopic small intestine biopsy

18. Screening for Celiac Disease (Slide 3 of 3)Genetic testing can be done to determine if a person may ever develop celiac diseasePatients with celiac disease carry one of both of the HLA DQ2 and DQ8 genes.30% - 40% of the population carries one or both of these genes as well. So, carrying either or both of these genes does not mean a patient will develop celiac disease.If a person does carry one or both of these genes, then he/she is at increased risk of developing celiac disease

19. Diagnosing Celiac DiseaseDiagnosis is based on clinical suspicion and confirmation with laboratory tests and duodenal biopsyEndoscopic duodenal biopsy is the gold standard for diagnosisPositive findings on biopsy include increased intraepithelial lymphocytes, loss of nuclear polarity, change from columnar to cuboid cells, lamina propria cellular infiltration, crypt elongation and hyperplasia, increased crypt mitotic index , and progressive villous flattening or blunting

20. Goals of TreatmentRelieving symptomsHealing the intestineReversing the consequences of malabsorptionCorrecting deficiencies in iron; folic acid vitamins D, E, A, and K; minerals such as magnesium, copper, zinc, and seleniumEnabling adherence to a healthy, interesting, gluten-free diet

21. Nonpharmacologic Therapy (Slide 1 of 4)Strict, lifelong adherence to a gluten-free diet is the only proven treatment for celiac diseaseEven very small amounts of ingested gluten can cause intestinal injuryWheat, barley, and rye must be avoidedOats have also been problematic and should not be eaten unless they are certified pure gluten-free oats and the consumption of oats if approved by the patient’s healthcare providerEncourage the consumption of naturally gluten-free foods of high nutritional valuePatients should be alerted to and avoid ingestion of gluten in nonfood products such as toothpaste, lip balm, and medications

22. Nonpharmacologic Therapy (Slide 2 of 4)Implementing a gluten-free diet is often very challengingA dietician is particularly helpful in educating about a gluten-free diet and assisting patients with adherenceCConsultation with a skilled dieticianEEducation about the diseaseLLifelong adherence to a gluten-free dietIIdentifying and treating nutritional deficienciesAAccess to an advocacy groupCContinuous long-term followup by a multidisciplinary team

23. Nonpharmacologic Therapy (Slide 3 of 4)Oral prescription medications, nonprescription medications, vitamin and mineral supplements, health and beauty aids, and cosmetics that have oral ingestion potential should not be overlooked as sources of glutenPharmacists should be actively involved in helping patient identify medications and supplements that contain gluten (so they can be avoided) and do not contain gluten

24. Nonpharmacologic Therapy (Slide 4 of 4)Newly diagnosed patients should be evaluated for nutritional deficiencies associated with vitamin and mineral malabsorptionCommon deficiencies include folic acid, vitamin B12, iron, calcium, fat soluble vitamins (e.g. vitamins D, E, A, and K) and some minerals Vitamin and mineral supplementation is typically recommended

25. Osteopenia and OsteoporosisMost adults with celiac disease are found to have some degree of bone lossAll patients should be screened for osteoporosis or osteopenia via dual-energy x-ray absorptiometry (DEXA) scanSupplementing a calcium-rich gluten-free diet with calcium, magnesium, and vitamin D may arrest or reverse celiac-related bone lossIn some patients, medications used to treat bone loss (e.g. bisphosphonates, selective estrogen receptor modulators, etc.) may be necessary

26. Pharmacologic TherapyDietary avoidance of gluten in the mainstay of celiac disease treatmentNovel pharmacologic treatments are under investigationMost instances of the use of pharmacotherapeutic agents is in response to refractory diseaseAgents with immunosuppressant effects such as corticosteroids, azathioprine, cyclosporine ,tacrolimus, infliximab, and alemtuzumab has been used in refractory celiac disease and reported in case reports

27. Evaluation of OutcomesDietary modification as described will usually result in rapid remission of symptoms with clinical improvement observed within days to weeks

28. References (Slide 1 of 2)Mangione RA and Patel PN. Chapter 27. Celiac Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.Patel PN, Mangione RA. Celiac Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw-Hill; 2017 . Crowe SE. Celiac disease. Ann Intern Med. 2011; 154(9): ITC5-1.

29. References (Slide 2 of 2)Binder HJ. Disorders of Absorption. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 19e New York, NY: McGraw-Hill; 2014.Celiac Disease Foundation.  www.celiac.org. Accessed February 24, 2017.