Gastroenterology Celiac Disease Courses in Therapeutics and Disease

Gastroenterology: Celiac Disease Courses in Therapeutics and Disease State Management Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Learning Objectives • Discuss the etiology and pathophysiology of celiac disease • Describe the gastrointestinal and extraintestinal symptoms of celiac disease • Differentiate between screening for and diagnosis of celiac disease • Explain who should be screened for celiac disease • Discuss treatment of celiac disease including nonpharmacologic and lifestyle measures Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Required Reading Patel PN, Mangione RA. Celiac Disease. In: Di. Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10 e New York, NY: Mc. Graw-Hill; 2017. Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

What is Celiac Disease? • Celiac disease is a small intestinal immune-mediated enteropathy caused by intolerance to ingested gluten • Gluten is a generic term for a variety of proteins found in grains such as wheat, barley, and rye – Link: Table on grains and other foods that do and do not contain gluten • Chronic inflammation caused by exposure to gluten leads to GI discomfort, nutrient malabsorption, and systemic complications • Celiac patients experience both GI and extraintestinal symptoms Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Epidemiology • Celiac disease is common in North America and Europe • It affects approximately 1% of Americans • The prevalence of celiac disease is higher in women than men at rates ranging from 2: 1 to 3: 1 • It is estimated that only 10% - 15% of those with celiac disease in the U. S. have been diagnosed Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Etiology (Slide 1 of 3) • Celiac disease occurs when a genetically predisposed person ingests gluten • Wheat gluten proteins exist in 2 fractions: gliadins and glutenins • Barley contains proteins called hordeins and rye contains proteins called secalins both of which are similar to glutenins • Ingestion of any of these proteins will lead to an autoimmune response in celiac disease patients Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

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 reported – Virtually all patients with celiac disease have variants of HLADQ 2 or HLA-DQ 8 molecules that are expressed on the surface of antigen-presenting cells Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Etiology (Slide 3 of 3) • Certain infectious agents and other compounds may contribute to the development of celiac disease – Adenovirus and hepatitis C viruses are thought to act as triggers – Campylobacter jejuni, Giardia lamblia, rotavirus, and enterovirus infections have been described in case reports as associated with celiac disease – Interferon-α has also been suggested to play a role in celiac disease development Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathophysiology (Slide 1 of 2) • Sensitive individual eats gluten inappropriate Tlymphocyte 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 Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathophysiology (Slide 2 of 2) • Link: Table on Proposed Pathophysiology of Celiac Disease • Link: Figure showing small-intestinal mucosal biopsies Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

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 asymptomatic • Clinical manifestations of celiac disease also vary between age groups – Link: Table on Selected Signs and Symptoms of Celiac Disease Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Signs and Symptoms (Slide 2 of 3) • Infants and young children – GI: Diarrhea, abdominal distention, vomiting, anorexia, and sometimes constipation – Extraintestinal: Failure to thrive, irritability • Older children and adolescents – GI: Diarrhea, abdominal distention, vomiting, anorexia, and sometimes constipation – Extraintestinal: Short stature, delayed puberty, anemia, neurologic findings (peripheral neuropathy, ataxia, seizure, migraine, dementia) Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Signs and Symptoms (Slide 3 of 3) • Adults – GI: Classic presenting sign is diarrhea accompanied by abdominal pain or discomfort – Other GI: Weight loss, constipation – Extraintestinal: iron-deficiency anemia, osteoporosis, neurologic symptoms, dermatitis herpetiformis, hypoproteinemia, hypocalcemia, elevated liver enzymes Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Dermatitis Herpetiformis (Slide 1 of 2) • Dermatitis herpetiformis is a skin manifestation of small intestinal immune-mediated enteropathy caused by the ingestion of gluten • It is characterized by an extremely pruritic, bullous skin rash generally found on the elbows, knees, buttocks, and scalp but can occur anywhere on the body • It 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 Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

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 disease • Link: Photograph of dermatitis herpetiformis of the face • Link: Photograph of bullous dermatitis herpetiformis Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

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 disease – First-degree relatives of people with celiac disease • Parents, siblings, and children have a 1 in 10 risk compared to 1 in 100 in the general population – Any individual with an associated autoimmune disorder or other associated condition • Examples 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 Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Screening for Celiac Disease (Slide 2 of 3) • Serologic tests screen for celiac disease antibodies – Serum Ig. A antibodies to tissue transglutaminase (t. TG) are increased in most cases of active celiac disease • This test is referred to as a t. TG-Ig. A test – < 4. 0 u/ml – Negative – 4 – 10 u/ml – Weak positive – > 10 u/ml – Positive – This test can be used to determine which patients should undergo a endoscopic small intestine biopsy Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Screening for Celiac Disease (Slide 3 of 3) • Genetic testing can be done to determine if a person may ever develop celiac disease – Patients with celiac disease carry one of both of the HLA DQ 2 and DQ 8 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 Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Diagnosing Celiac Disease • Diagnosis is based on clinical suspicion and confirmation with laboratory tests and duodenal biopsy – Endoscopic duodenal biopsy is the gold standard for diagnosis – Positive 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 Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Goals of Treatment • • Relieving symptoms Healing the intestine Reversing the consequences of malabsorption Correcting deficiencies in iron; folic acid vitamins D, E, A, and K; minerals such as magnesium, copper, zinc, and selenium • Enabling adherence to a healthy, interesting, gluten-free diet Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Nonpharmacologic Therapy (Slide 1 of 4) • Strict, lifelong adherence to a gluten-free diet is the only proven treatment for celiac disease – Even very small amounts of ingested gluten cause intestinal injury – Wheat, barley, and rye must be avoided – Oats 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 provider – Encourage the consumption of naturally gluten-free foods of high nutritional value – Patients should be alerted to and avoid ingestion of gluten in nonfood products such as toothpaste, lip balm, and medications Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Nonpharmacologic Therapy (Slide 2 of 4) • Implementing a gluten-free diet is often very challenging • A dietician is particularly helpful in educating about a gluten-free diet and assisting patients with adherence C E L I A C Consultation with a skilled dietician Education about the disease Lifelong adherence to a gluten-free diet Identifying and treating nutritional deficiencies Access to an advocacy group Continuous long-term followup by a multidisciplinary team Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

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 gluten • Pharmacists should be actively involved in helping patient identify medications and supplements that contain gluten (so they can be avoided) and do not contain gluten Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Nonpharmacologic Therapy (Slide 4 of 4) • Newly diagnosed patients should be evaluated for nutritional deficiencies associated with vitamin and mineral malabsorption – Common deficiencies include folic acid, vitamin B 12, iron, calcium, fat soluble vitamins (e. g. vitamins D, E, A, and K) and some minerals – Vitamin and mineral supplementation is typically recommended Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Osteopenia and Osteoporosis • Most adults with celiac disease are found to have some degree of bone loss • All patients should be screened for osteoporosis or osteopenia via dual-energy x-ray absorptiometry (DEXA) scan • Supplementing a calcium-rich gluten-free diet with calcium, magnesium, and vitamin D may arrest or reverse celiacrelated bone loss • In some patients, medications used to treat bone loss (e. g. bisphonates, selective estrogen receptor modulators, etc. ) may be necessary Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pharmacologic Therapy • Dietary avoidance of gluten in the mainstay of celiac disease treatment • Novel pharmacologic treatments are under investigation • Most instances of the use of pharmacotherapeutic agents is in response to refractory disease • Agents with immunosuppressant effects such as corticosteroids, azathioprine, cyclosporine , tacrolimus, infliximab, and alemtuzumab has been used in refractory celiac disease and reported in case reports Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Evaluation of Outcomes • Dietary modification as described will usually result in rapid remission of symptoms with clinical improvement observed within days to weeks Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

References (Slide 1 of 2) • Mangione RA and Patel PN. Chapter 27. Celiac Disease. In: Di. Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9 e. New York, NY: Mc. Graw-Hill; 2014. • Patel PN, Mangione RA. Celiac Disease. In: Di. Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10 e New York, NY: Mc. Graw-Hill; 2017. • Crowe SE. Celiac disease. Ann Intern Med. 2011; 154(9): ITC 5 -1. Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

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, 19 e New York, NY: Mc. Graw-Hill; 2014. • Celiac Disease Foundation. www. celiac. org. Accessed February 24, 2017. Author: Monica L. Skomo, B. S. , Pharm. D. , BCACP, CTTS; Assoc. Prof. of Pharmacy Practice; Dir. of Assessment and Educational Strategies; Duquesne University School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved