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An Academic Research Center of Excellence
january - february
2008
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aware
Celiac Disease:
C
eliac (from the Greek work koilia meaning belly or abdomen) disease (CD) affects approximately 1% of the population in the United States. Almost 60,000 Americans are newly diagnosed each year and the number of cases appears to be increasing. CD is also referred to as celiac sprue (Dutch word meaning a disease associated with diarrhea, malabsorption, weight loss, etc.), non-tropical sprue, and gluten-sensitive enteropathy. The disease occurs throughout Europe as well as the Middle East, Asia, South America, and North Africa. Women are 2-3 times more likely to develop CD; however, this ratio diminishes after the age of 65 years. It potentially can affect many organ systems and may occur at any age including infancy. CD is an inflammatory, autoimmune disorder that generally involves the upper part of the small intestine. The disease is precipitated by ingestion of various proteins found in grains such as wheat, barley, and rye. The term gluten is used to identify this rather diverse group of grain proteins that produce the symptoms of CD. Elimination of these grain proteins from the diet is the key factor in management of the condition. There is a genetic predisposition for CD and firstdegree relatives of patients with the disease should be tested.
What Causes Celiac Disease? There are many factors that contribute to the eventual development of CD. As mentioned earlier, family history of the disease must be considered. There is some evidence that the risk of CD may be reduced if the child is breastfed. On the other hand, intestinal infection or administration of gluten-containing cereals prior to four months of age may increase the risk of disease. Ingestion of gluten triggers the immune response in susceptible individuals that results in damage to the small intestine. Gliadin is the major fraction of protein in wheat that is responsible for the development of CD. Other protein components of barley and rye produce similar effects in these patients. The small intestine is lined with tiny, hair-like projections known as villi (see accompanying
Watch What You Eat!
figure) whose function is to absorb nutrients, vitamins, minerals, fluids, etc. When gluten
Villi in the Small Intestine Villi Small intestine
From: NDDIC http://digestive.niddk.nih.gov/ddiseases/pubs/celiac/ (accessed 7 December 2007)
is ingested by a person with CD, an immune reaction occurs in the small intestine leading to inflammation and destruction of villi. This results in an inability to adequately absorb fat, protein, vitamins, minerals, fluids, and other substances required to maintain normal health. The complex immune inflammatory response in CD is not completely understood, but the key factor appears to be the recognition of gliadin and similar proteins as foreign substances. The patient’s immune system responds by activating cells known as lymphocytes. These specialized cells release chemicals that produce inflammation and subsequent injury of villi and other tissue in the small intestine. Antibodies are also produced and contribute to the overall destructive process associated with CD.
Signs and Symptoms There are some differences in the frequency of signs and symptoms of CD in children and adults (see Table 1). Diarrhea appears common in both groups while the occurrence of abdominal pain or distention is variable. Children may present with short stature and infants may fail to thrive. Onset in children usually occurs after the addition of cereal to the diet. In adults, weight loss, oral ulcers, and reduced blood levels of protein and calcium may also be observed. Iron deficiency anemia and osteoporosis are also commonly associated with CD in adults. Dermatitis herpetiformis continued on back
Celiac Disease: Watch What You Eat! is a type of rash that can be linked to the ingestion of gluten. It is characterized by the appearance of groups of small blisters on the knees, elbows, back, etc., and is usually accompanied by severe pruritus (itching). Patients with dermatitis herpetiformis frequently do not have the intestinal involvement associated with CD. Rare complications of CD include cancer of the small intestine, esophagus, or liver. Occasionally, patients continue to have severe symptoms even though gluten has been completely eliminated from the diet. This is referred to as refractory sprue or refractory CD.
Diagnosis CD may be difficult to diagnose if only based on the patient’s signs and symptoms. Blood tests to identify specific antibodies play a key role in the diagnosis of this disease. One of the most important of these blood examinations identifies the presence of endomysial (connective tissue in the small intestine) antibody while the other tries to detect antibody directed against tissue transglutaminase (an important enzyme present in the injured part of the intestine). The presence of these antibodies is associated with nearly 100% diagnostic accuracy. Biopsy (removal of a small amount of tissue for examination under a microscope) is still considered the gold standard for a diagnosis of CD.
Treatment Lifelong adherence to a gluten-free diet is the only accepted treatment for CD (see Table 2). Patients should seek help from a skilled
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aware
A publication of: Mylan School of Pharmacy Center for Pharmacy Care Pharmaceutical Information Center (PIC) Additional information on newsletter topics: Pharmaceutical Information Center 412-396-4600 pic@duq.edu Questions about screenings or programs: Christine O’Neil, Pharm.D, B.C.P.S. 412-396-6417
dietician to maintain proper nutrition and adhere to a lifestyle free of wheat, barley, and rye. Oats are generally tolerated by people with CD; however, caution must be used because most commercially available oats may be contaminated with gluten-containing grains during milling and transportation. Meats, dairy products, fruits, and vegetables are naturally gluten-free. Many people find it difficult to dine outside of the home while remaining committed to the diet; however, noncompliance will likely result in recurrence of symptoms. Vitamin supplementation is advised to prevent deficiencies in patients with CD. Patients must also be aware that gluten may be an inactive ingredient in many prescription and over-the-counter (OTC) drugs as well as dietary supplements, vitamins, etc. Gluten-containing substances may be incorporated as inactive ingredients in capsules and tablets. They serve as binders, stabilizers, or enhance the flow of ingredients in tablet machines. No current law requires the listing of gluten-
containing ingredients in pharmaceutical preparations. In many cases, the patient or a healthcare professional will have to contact the specific manufacturer to determine the gluten status of an individual product. Two Web sites that include lists of gluten-free pharmaceuticals are Gluten Free Drugs http://www.glutenfreedrugs.com/ and Wheaton Group- Partial List of Gluten-free Medications, Nutritional Products, and Vitamins http://homepage.mac.com/ sholland/celiac/GFmedlist.pdf/. Celiac disease is becoming increasingly recognized in the United States. Adherence to a gluten-free diet is critical to its successful management and prevention of recurrence. The Web sites listed at the end of this article provide a great deal of information on CD. Lastly, there are many patient support groups scattered throughout the country. In the Pittsburgh area, information on CD may be obtained from the Greater Pittsburgh Celiac Sprue Support Group (www. pittsburghceliacs.org).
Table 1: Signs and Symptoms of Celiac Disease
Signs and Symptoms (Adults) Abdominal pain Arthralgia Diarrhea Infertility or recurrent spontaneous abortion Iron deficiency anemia Irritable bowel syndrome Peripheral neuropathy Persistent fatigue Weight loss
Signs and Symptoms Associated Conditions (Children) Abdominal distention/ bloating Diarrhea Delayed puberty Growth failure
Autoimmune disorders Dermatitis herpetiformis Down Syndrome Epilepsy Immunoglobulin A deficiency Microscopic colitis Osteoporosis or other bone disease Thyroid disease Turner syndrome Type 1 diabetes mellitus
Adapted from: Westerberg DP, Gill JM, Dave B, et al. JAOA 2006;106:145-51
Table 2: Presence of Gluten in Various Grains Grains to avoid Barley Rye Wheat
Safe Grains Gluten-free Starches Buckwheat Corn Oats Rice Sorghum
Chickpeas Tapioca Lentils Beans Nuts -Navy Potato -Kidney Seeds -Soy
Adapted from: Green P, Cellier C. Celiac disease. N Engl J Med 2007;357:1731-43
www.pharmacy.duq.edu For additional information on Celiac Disease, visit the following Web sites:
Newsletter Contributors
• http://www.csaceliacs.org/
John G. Lech, Pharm.D. Sabrina A. Chirumbolo, Pharm.D. Candidate Lance R. Olszewski, Pharm.D. Candidate
• http://www.nlm.nih.gov/medlineplus/celiacdisease.html
• http://digestive.niddk.nih.gov/ddiseases/pubs/celiac/ • http://celiac.nih.gov/ 1/08 318433 CG