The Community Pharmacist s Role In Celiac Disease

Transcription

1 continuing education The Community Pharmacist s Role In Celiac Disease By Nicole Marcotullio, PharmD U pon completion of this article, the pharmacist should be able to: 1. Explain the etiology and diagnosis of celiac disease. 2. Identify the signs and symptoms of celiac disease and associated conditions. 3. Describe potential food and medications sources of gluten and how community pharmacists can counsel patients. 4. Discuss non-pharmacologic and pharmacologic treatments as they relate to celiac disease 5. I dentify factors that would influence product selection in the community pharmacy setting Etiology and Pathophysiology Most commonly referred to as celiac disease (CD), this condition was first described in the second century but was not fully understood and identified until the 20th century. Other associated references include celiac sprue, non-tropical sprue, and gluten-sensitive enteropathy. Celiac disease is an autoimmune gastrointestinal disorder that causes the immune system (IgA mediated) to damage and attack the mucosal lining or villi of the small intestine. The small intestine, which is about 20 feet long, is the section of the gastrointestinal tract between the stomach and the large intestine which normally completes the process of digestion, absorbs nutrients, and passes any residue on to the large intestine. Villi are tiny, fingerlike protrusions that line the small intestine. The villi normally allow nutrients from food to be absorbed into the bloodstream. The inflammation noted in CD patients is an adverse reaction to gluten, Useful Websites a protein found in grains such as wheat, barley, rye, and (to a lesser extent) oats that American Celiac Disease Alliance contains particular amino acid sequences that are harmful to persons with CD. The American Dietetic Association alcohol-soluble fraction of gluten proteins stimulates the activation of T-cells, causing Food Allergy Network an inflammatory response and damage to the intestinal villi. The Celiac Disease Foundation The autoimmune response of CD results in inflammation, injury, and resulting villous The Essential Gluten-free Restaurant Guide atrophy to the mucosal lining of the proximal part the small intestines. Without healthy villi, National Foundation for Celiac Awareness nutrients will pass through the small intestine without being absorbed, with a potential to cause malnutrition. Gluten is actually a general term for storage proteins found in grains. Each grain has its own protein: gliadin in wheat, secalin in rye, hordein in barley, avenin in oats, zein in corn and oryzenin in rice. However, in CD only the proteins found in wheat, barley, rye, and oat have been shown to cause the inflammation and symptoms of CD. Gluten therefore is a generic term used to identify the group of grain proteins that causes the symptoms of CD. In contrast, the proteins found in rice and corn do not cause this inflammatory process. CD is an inherited disease and affects approximately 1 percent of the population in the United States. The number of newly diagnosed cases appears to be increasing, with nearly 60,000 cases diagnosed annually, with an incidence that has increased fourfold over the past 50 years. The May 2011 america s Pharmacist 33

2 disease occurs throughout the United States, as well as Europe, the Middle East, Asia, South America, and North Africa. However, Caucasians of northern European descent tend to have the highest prevalence, with reports of CD affecting as many as 1: Europeans and 1:250 Americans. With an estimated 3 million people affected by the disease, a staggering 95 percent are thought to currently be undiagnosed. Unfortunately, CD is not just a disease of isolated gastrointestinal symptoms. If left untreated, CD can increase a person s risk of other autoimmune diseases, osteoporosis, thyroid disease, cancer, type 1 diabetes, and reproductive health issues. There appears to be a genetic predisposition through genetically transmitted histocompatibility cell antigens. The Human Leukocyte Antigen (HLA) genes specifically linked to celiac disease are DQ2 and/or DQ8, and the majority of people with CD (90 95 percent) express the DQ2 molecule. Most CD patients express both HLA genetic markers and CD is unlikely in those that do not have the HLA typing. Also noteworthy is that CD shares a common genetic risk region with other autoimmune conditions, including type 1 diabetes (HLA-DQ), thyroid disease, and rheumatoid arthritis. Type 1 diabetes and CD share multiple genetic loci such as HLA-DR3 and HLA-DQ2 (HLA-DQ8). Women are also two to three times more likely than men to develop CD. This gender predisposition does tend to lessen after the age of 65. However, the onset of the disease can occur at any age from infancy to adulthood and affect both men and women. If an infant does develop CD, symptoms will typically be seen within the first four to 24 months of age. This age range is thought to be potentially associated with the timing of the introduction of gluten containing cereal to the infants diet. Due to this potential trigger there is limited evidence that the risk of CD, in those genetically susceptible, is reduced if the child is breastfed for a longer duration and is increased if the child is introduced to gluten-containing cereals prior to four months of age. Reported strategies include gradually introducing gluten containing foods while infants are still breast-feeding. Other factors that are speculated to play a role in the timing of disease onset include the age a person started eating gluten-containing foods and the amount of gluten-containing foods ingested. While this genetic disorder can sometimes emerge in childhood, not all genetically susceptible people will ever go on to develop CD symptoms. It is thought that some form of environmental trigger causes the onset of symptoms in those genetically susceptible. These triggers are not fully identified or understood and thought to be precipitated by a myriad of events including extreme emotions, stress, surgery, viral or bacterial infection, pregnancy, childbirth, puberty or other environmental factors. Generally considered a benign condition if it is not treated and goes undiagnosed, affected patients are at risk of developing other autoimmune diseases, osteoporosis, or thyroid disease. There have also been reports of a small increase in mortality rates due to the risk of malignancy, including esophageal cancer, melanoma, non-hodgkin lymphoma, and small intestine adenocarcinoma. Diagnostic Testing It is not currently recommended to routinely screen people for CD, especially if they are asymptomatic. Unfortunately a large portion of people with CD go undiagnosed. A large screening conducted in Italy looked at 17,201 children ages 6 to 15 to identify the prevalence of CD in this population. The prevalence was 1:184 and the ratio of undiagnosed to diagnosed CD was significant at 7:1. There have also been studies describing an increase in prevalence of CD with age. A survey conducted in Italy identified that approximately 15 percent of newly diagnosed CD patients were over the age of 65 and often suffered from symptoms for more than 11 years prior to their diagnosis. This may be due to the nondescript symptoms that can appear similar, and are often misdiagnosed as, other conditions such as inflammatory bowel disease, irritable bowel syndrome, GERD, chronic fatigue syndrome or patients that simply do not seek medical attention for their symptoms. However, with advances in screening and awareness of the disease, more people are being appropriately identified and diagnosed. Various testing methods are recommended to confirm the diagnosis, including serologic studies, a trial of a gluten-free diet, and confir- 34 america s Pharmacist May

3 mation through endoscopy with a small bowel biopsy. In counseling patients it is important to instruct them not to go on a gluten-free diet prior to a biopsy or antibody testing, as this may cause the antibody levels to appear normal as well as improve the intestinal villi, resulting in a false negative result. Serologic studies consist of autoantibody testing for anti-tissue transglutaminase (IgA ttg), total serum IgA and anti-endomysial antibody (IgA EMA). The antibody testing will determine the level of response a person is having to the gluten protein. Positive results are indicated by high antibody levels. Initially IgA ttg should be analyzed, with increased levels seen in CD. Tissue transglutaminase, the target auto-antigen contained within the endomysium, demonstrates specificity of greater than 95 percent and sensitivity in the range of 90 percent to 96 percent, especially in cases of moderate to severe CD. IgA ttg testing is often performed over the gliadin antibody test due to its accuracy, reliability and low cost, and is considered the preferred method of serologic detection. Similarly, IgA EMA analysis may also be performed but has a slightly lower and variable sensitivity but an excellent specificity (99.6 percent). Although the IgA EMA testing method is accurate, it poses a greater error potential, is operator dependent, is more time consuming, and is also more expensive to conduct compared to IgA ttg. Finally, IgG ttg analysis may be useful in patient with a known IgA deficiency. However, the prevalence of IgA deficiency in CD patients is low and routine testing is not recommended unless IgA deficiency is known or highly suspected. Testing of IgA EMA or IgA ttg should be the first step in the process of diagnosis, and the presence of these antibodies are useful to identify patients likely to have CD. To confirm the diagnosis, however, further workup through a small intestine biopsy is required. The small bowel biopsy through an upper endoscopy is the gold standard for the diagnosis of celiac disease. The endoscopy is performed through the patient swallowing a small flexible instrument with a camera. The camera allows a physician to examine the upper part of the gastrointestinal system and remove a small piece (biopsy) of the small intestine. The biopsy is not painful to the patient. Normally the intestinal mucosal lining has distinct finger-like structures called villi, which are responsible for allowing the small intestine to absorb nutrients. In patients with CD the villi will appear flattened with elongated intestinal crypts, villous atrophy, and increased intraepithelial lymphocytes. Fortunately this damage is not permanent, and once a patient stops eating gluten the villi can resume a normal growth pattern, with approximately 70 percent of people experiencing improvement of symptoms within two weeks of going on a gluten-free diet. The villi may take longer to fully recover and return to a normal functional capacity, and may take anywhere from six months to two years to fully recover. Due to the genetic predisposition, patients with relatives with a positive diagnosis have a greater chance of also being diagnosed, with a prevalence of about 10 percent in first degree relatives, and 2.6 percent to 5.5 percent in second degree relatives. Therefore, it is recommended that first degree and in some cases second degree relatives of patients with the disease be tested, especially if they exhibit signs or symptoms. An additional diagnostic tool is through testing of the genetic marker for HLA DQ2 and/or DQ8. This is useful for two reasons; to help confirm a diagnosis in a patient that has positive auto-antibodies, and to screen family members of those without symptoms to see if they are at risk of developing CD. As mentioned earlier, it is virtually impossible to have CD if you do not have these genes, but it is important to emphasize that simply because a patient has the gene does not mean they will go on to develop the disease. However, this does put them at a higher risk and further testing would be warranted, especially if they exhibit clinical signs and symptoms of the disease. For follow-up testing, one method to determine if the gluten-free diet is working is to monitor the levels of antibodies in the blood. If levels decline on a gluten-free diet, this indicates that the diet has been effective. Due to the malabsoptive nature of the condition additional testing may be performed to identify iron, folate, calcium, and vitamin D deficiencies. May 2011 america s Pharmacist 35

4 Signs and Symptoms CD most often presents with three classic signs and symptoms: villous atrophy, symptoms of malabsorption (such as steatorrhea, weight loss, or other signs of nutrient or vitamin deficiency), and resolution of the intestinal lesions and symptoms within weeks to months after gluten-containing foods are withdrawn from the diet. Although these are the classic signs, it is important to note that signs and symptoms may present differently between children and adults, and some patients may present with only atypical symptoms. The classic gastrointestinal signs include diarrhea with bulky, foul-smelling, floating stools due to steatorrhea, flatulence, and meteorism (due to colonic bacterial digestion of malabsorbed nutrients). Due to malabsorption and nutrient deficiency, patients may also develop growth failure (especially in children), weight loss, anemia due to faulty uptake of iron and/or folic acid, neurologic disorders from deficiencies of B vitamins, and osteopenia from deficiency of vitamin D and calcium absorption. CD can also present as atypical symptoms such as fatigue, borderline iron deficiency, elevations in serum aminotransferases, bleeding (gums) or bruising due to low Vitamin K, and can range from mild to severe. This can present a challenge in identifying CD patients, especially those that should go on for further testing. Refer to Table 1 for a more comprehensive list of signs and symptoms. Associated Conditions Other disorders have been identified as having a greater risk of development in patients with CD. The autoimmune disorders type I diabetes mellitus (2 8 percent), Down syndrome (3 12 percent), Turner syndrome (2 10 percent), ulcerative colitis, autoimmune thyroiditis ( percent), and rheumatoid arthritis show a greater prevalence in these patients. Other non-gastrointestinal manifestations of CD include infertility (male and female), miscarriages, menstrual irregularity, rheumatic disorders, liver disease, thyroid disease (hypothyroid more than hyperthyroid), pancreatitis, osteopenia (40 percent), osteoporosis (10 30 percent), depression (10.6 percent), epilepsy (3.5 percent), migraine headaches (3.2 percent), anxiety (2.6 percent), suicidal tendency (2.1 percent), carpal tunnel syndrome (1.8 percent), and myopathy (1.5 percent). Lactose intolerance is common in CD patients, especially those that are undiagnosed and untreated. Cancers, particularly non-hodgkin s lymphoma, may also occur as a complication of the disease. Although people with CD may have no symptoms at all, damage can still be occurring to the intestinal tract, which can ultimately lead to complications of malnutrition About percent of CD patients are estimated to have an associated skin condition known as dermatitis herpetiformis (DH), but almost all patients (90 percent) who present with DH have some form of CD. DH is a skin rash that can appear anywhere but is most likely found on the elbows, knees, buttocks, lower back, face, neck, trunk, and occasionally within the mouth. The blisters appear round and red with a raised, fluid filled center and are extremely itchy. The itchiness usually resolves when the blister is ruptured due to itching and scratching. The diagnosis of DH is made through a skin biopsy which shows IgA deposits along the sub-epidermal basement membrane. CD in patients with DH is often asymptomatic and most patients with DH tend to have less severe digestive symptoms. The combination of skin manifestations and potentially less severe gastrointestinal symptoms has lead to DH being mistakenly diagnosed as eczema, psoriasis, or other forms of dermatitis. DH and the skin lesions will most likely resolve through adherence to a gluten-free diet with the most significant improvement seen within several weeks, but can also be treated with antibiotics (commonly dapsone). Dapsone will help alleviate the itching and rash, but it is important to note that it will not prevent intestinal damage or heal the lining of the small intestine if the person continues to ingest gluten. Nonpharmacologic and Pharmacologic Treatment Options The most effective way for patients to treat their CD is to adhere to a strict gluten-free diet. Medication treatment for CD is not necessary in most cases due to the dramatic improvement of symptoms (days to weeks) on a gluten-free diet. Some patients may experience refractory disease (7 percent to 19 percent) despite strict adherence to a gluten-free diet or experience 36 america s Pharmacist May

5 Table 1: Signs and Symptoms of Celiac Disease Children Adults Common Features Diarrhea, anorexia, failure to thrive (especially infants), abdominal distention/flatulence, irritability, delayed puberty, steatorrhea (fatty stool), vomiting Iron-deficiency anemia, diarrhea Less Common Features Short stature, aphthous stomatitis (mouth sores), abdominal pain, dental enamel defects, folate-deficiency anemia, osteoporosis, vitamin K deficiency, thrombocytosis, arthralgia, epilepsy, infertility, anxiety and depression, alopecia, dermatitis herpetiformis, fatigue, liver abnormalities, tingling and numbness, joint pain ** Patients with CD may exhibit one or more of the following signs and symptoms and children may also experience signs and symptoms that are listed for adults. celiac crisis, which presents as severe diarrhea, dehydration, weight loss, acidosis, hypocalcemia, and hypoproteinemia. In these cases patients may be treated with corticosteroids such as prednisone, or other immunosuppresants such as azathioprine, infliximab, or cyclosporine. CD may create problems with vitamin and mineral absorption. Supplemental products of calcium, vitamins A, B12, D and E, folate and iron should be recommended to ensure adequate nutrition in these patients. Treatment strategies under investigation involve the use of recombinant enzymes that digest gliadin in the stomach or small intestine. Other possible treatment options being explored involve therapies that interfere with the immune response, and vaccines that desensitize patients to the gluten proteins through the use of immune response causing peptides. Gluten-Free Diet One of the biggest challenges for patients diagnosed with CD is adhering to a strict gluten-free lifestyle. The reason this can be so difficult, in addition to the significant change in eating habits and product selection, is that gluten is often hidden in prepared foods, supplements, cosmetics, and medications as additives, binders, and flavorings. The rationale behind the recommendation of a strict gluten-free diet is that some patients will not have symptoms with minimal amounts of gluten, but the underlying intestinal damage may still be occurring. Adhering to a gluten-free diet is a major lifestyle modification that may not only affect the patient but also family and friends. Consulting a dietitian may be an excellent first step in learning how to avoid foods while maintaining a balanced diet, learning strategies for shopping and preparing food, and identifying lifestyle resources. Education is especially helpful when a patient is diagnosed at an older age, is the first person in a family to have the disease, or is a child where proper nutritional intake during development and prevention of the malabsorption of nutrients due to uncontrolled disease is important at an early age. Other excellent resources for patients are celiac medical centers, organizations, and support groups. Refer to Table 5 for a list of resources. Sources of Gluten Gluten is found in a variety of foods and other products and may also be used as an additive in products such as lipstick, Play-Doh, and medications. Gluten typically found in food is responsible for the doughy, spongy, and elastic texture of foods. To expose a patient to the harmful effect of gluten, it must be ingested or swallowed, and is not thought to be able to be absorbed through the skin. Therefore, items like shampoo and lotions which can contain gluten are considered safe for CD patients. However, extraneous exposure to gluten may occur when products that may contain gluten (like lipstick) may be ingested, or when children play with putty or Play-Doh and then stick their fingers in their mouth. Table 2 contains a list of sources of gluten, and processed foods that may contain wheat, barley or rye. Table 3 contains a list of gluten-free foods. Dining out can potentially pose a challenge due to the lack of readily available information of ingredients that May 2011 america s Pharmacist 37

6 are found in the meal, and also used in food preparation. Fortunately, an increasing number of restaurants are providing gluten-free menus that identify the items that are safe to ingest, or provide substitute choices that allow a patient to order the meal to avoid gluten. For example, some restaurants will provide separate menus that advise that consumers can order the vegetables but not with the seasoning or the sauces that normally accompany the dish. Alerting the restaurant staff also allows the chef to avoid preparing food in areas that come in contact with gluten, or modify the ingredients used in preparation of the meal. Another example is beef prepared at a steakhouse. Some restaurants will dust the beef in flour before cooking it, which would not be evident from simply reading the menu. Table 2: Source of Gluten and Processed Food That May Contain Wheat, Barley, or Rye. Sources of Gluten* Brown Rice Syrup Malt, malt flavoring, malt vinegar (are generally made from barley, verify the source) Wheat (einkorn, emmer, durum, farina, faro, graham, kamut, semolina, spelt) Breading and coating mixes Matzo Couscous (granules of semolina made from durum wheat) Barley Rye Wheat (starch, bran, germ) Cracked wheat, hydrolyzed wheat protein Flour (bromated, durum, enriched, graham, phosphate, plain, selfrising, white) Triticale (cross between wheat and rye) Processed Foods or Products that May Contain Wheat, Barley, or Rye* Seasoned chips, nuts (i.e. Cold cuts, hot dogs, Rice pilaf Self basting turkey/chicken barbeque, nacho flavor, seasoned tortilla chips) salami, sausage Drink mixes Croutons Medications, vitamins, Energy bars supplements Beers/lagers Dairy substitutes Imitation seafood Marinades Cereal (wheat starch, barley malt) Imitation bacon Processed lunch meats (some will specifically list if they are gluten-free) Sauces, gravies Salad dressings Pastas Stuffing Thickeners Soy sauce Soup bases (i.e. chicken/ Bouillon cubes Putty, play dough, glue beef stock) (wash hands) Communion wafers Candy (i.e. candy coating, licorice) French fries (verify using different oil then what deep-frying breaded foods) Chapstick, lipstick, lipgloss Seasonings, spice blends Toothpaste Chocolate milk Cheese spreads Dried fruit (dusted with Envelope glue (don t lick Tea (flavored) Oats flour) the seal) Baked beans * Most of these foods can be found gluten-free. When in doubt, check with the food manufacturer. (Not an all inclusive list) 38 america s Pharmacist May

7 Table 3: Gluten-Free Foods Arrowroot Flax Rice flour and rice (white, brown and wild) Almond meal flour Guar Gum Rice bran Amaranth Indian Rice Grass Seed flours (i.e. sesame) Beans, bean flours(garfava, romano) Legumes Sago Buckwheat Millet Sorghum flour Coconut flour Nuts and Nut flours (i.e., almond, hazelnut, pecan) Soy and soy flour (NOT soy sauce unless specified as gluten-free) Cassava Pea flour Tapioca, tapioca starch Corn Potatos, potato starch, potato Teff flour Distilled alcohols (unless flavoring is added after) Quinoa Yucca Another dietary and health concern with maintaining a gluten-free diet is that most glutenfree cereals, pastas and breads are not fortified with essential vitamins, and can have insufficient amounts of iron and B vitamins. Patients may benefit from taking supplemental vitamins. Patients may also gain weight (20 40 percent overweight) on a gluten-free diet. This is due to a combination of factors. One positive factor is the tendency for some patients to rely excessively on high protein or fatty foods to supplement their diet in order to avoid gluten. Furthermore, the avoidance of most grains and the resulting low fiber diet associated with some gluten-free foods can result in patients developing constipation or exacerbation of irritable bowel symptoms. Coexistence of other food intolerance is also likely. The most common concomitant food intolerance is lactose, but soy and fructose intolerance is also notable. A common question which is usually associated with understanding the challenges of complete avoidance of gluten is the speculation as to a threshold for the amount of gluten that will not cause mucosal damage. This is of concern because there is a level of cross contamination of products due to food preparation and manufacturing that Table 4: Gluten-Free Ingredients and Gluten Containing Ingredients Gluten-Free Ingredients Starches specifically from corn (most common) or potato Sweeteners (uncontaminated) from sucrose, honey, dextrose, fructose, corn syrup Uncontaminated Acacia Agar Alginates Carrageenan Tapioca Gellan Guar gum Xanthan gum Cellulose and cellulose derivatives Other polymers Gluten Containing Ingredients Any ingredient derived from barley, barley malt, rye, or wheat (refer to Table 2 for a complete list) Whole grains Grain Flour Unspecified sources of: starch, starch grain, pregelatinized starch, modified food starch, dextrates, dextrin, dextrimaltose, carmel coloring, botanical sources of starches. Other possible sources: vegetable gum May 2011 america s Pharmacist 39

8 Table 5: Celiac Centers and Celiac Experts Childrens Hospital Los Angeles childrenshospitalla.org The Kogan Celiac Center St. Barnabas Ambulatory Care Center Celiac Disease Program University of Chicago Celiac Disease Center Columbia University The Celiac Center at Paoli Hospital Alfred I dupont Hospital for Children Pediatric GI Division Thomas Jefferson University Hospital jeffersonhospital.org Wm K. Warren Medical Research Center For Celiac Disease celiaccenter.ucsd.edu University of Tennessee Medical Center Celiac Center Celiac Disease Clinic Celiac Disease and Inflammatory Bowel Disease Center Center for Celiac Research University of Maryland School of Medicine University of Virginia Digestive Health Center of Excellence Celiac Disease nutrition/celiacsupport.cfm Childrens Hospital of Wisconsin Bonnie Mechanic Celiac Disease Clinic Center for Celiac Disease Beth Israel Deaconess Medical Center Celiac Disease Clinic Mayo Clinic may be difficult to detect, and in some cases is unavoidable. A systematic review conducted by Akobeng, A.K. et. al, identified that 200 parts per million (ppm) of gluten did appear to cause mucosal damage in CD patients, and that a lower concentration should be used in products that claim to be gluten-free. However, there are differing reports of what is exactly considered the maximum tolerable amount of gluten that would avoid symptoms and mucosal damage in CD patients. Some reports stated that complete avoidance is the only acceptable approach to ensure that no mucosal damage is occurring. Other studies reported that patients who consumed an average of 30 mg of gluten per day (100 ppm) did not develop histological abnormalities. Catassi and colleagues reported that the ingestion of 50 mg/day induced histologic changes after three months of exposure, but 10 mg of gluten/day appeared safe for most of the subjects studied. Based on these findings, they concluded that 20 ppm would be the safest and most conservative threshold to recommend for gluten-free products. Catassi did note that CD patients respond individually to small amounts of gluten, which raises the question of whether a standard number of acceptable gluten can be determined or if each individual patient should be managed based on their response. The challenge with determining an exact number, which was demonstrated in the review article, is that there appears to be variability in the level of symptoms of celiac patients and the degree of sensitivity and amount of gluten that can be tolerated. Resources including the Food and Drug Administration and Codex Alimentarius guidelines consider a product to be gluten-free if it contains less than 20 ppm (6 mg) of gluten, whereas the National Food Authority determined that there should be no gluten found in the products, and if it contains less than 200 ppm of gluten it is considered to have low gluten. To put this into perspective 20 ppm is the same as 20 mg/kg of food, or 20 milligrams of 40 america s Pharmacist May

9 gluten per ounces of food. Therefore, a 1-ounce (28.35 grams) slice of gluten-free bread containing 20 ppm of gluten would contain 0.57 milligrams of gluten. Assuming a daily diet of 1,800 2,000 calories, consumers should eat six 1-ounce grain equivalents each day. Six ounces of grain food containing 20 ppm gluten would contain 3.42 mg of gluten daily. Based on the variation in response of CD patients, lack of an accurate method to detect gluten, and scientific evidence, further research is needed to determine an acceptable amount of gluten that can be tolerated. This is especially important to ensure consistency in products that claim to be gluten-free. Adhering to a gluten-free diet may appear difficult due to the extensive list of foods containing gluten and all of the possible products with hidden gluten. Fortunately, a gluten-free diet has become easier over the years, due in part to the increasing availability of glutenfree foods in local grocery stores, farmers markets, specialty grocers, and organic food stores. These stores have sections devoted to gluten-free products to assist in identifying the products for CD patients. If a store does not specifically have a gluten-free section, these products may be available in the organic food aisle. In addition, several food manufacturers are directly listing allergy information in the ingredients section or on the front of the package. The reason for improved labeling is was due to the Food Allergen Labeling and Consumer Protection Act (FALCPA), a bill that was passed in FALCPA determined eight major foods or food groups accounting for 90 percent of food allergies: milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat, and soybeans. According to the FDA, many parents of children with a food allergy were unable to correctly identify in each of several food labels the ingredients derived from major food allergens. As a result, FALCPA requires food manufactures to clearly label if a food product contains protein derived from any of listed food allergens. This law applies to packaged foods imported and domestically manufactured that are subject to FDA regulation; however, does not include meat, poultry, and egg products. Under FALCPA, a food product may be subject to recall if it contains one of the major food allergen as an ingredient that is not properly identified on the food label. Although FALCPA was passed in 2004, food manufacturers were given a two-year window to update their labels in accordance with the new requirements. One limitation to FALCPA is that it did not require food manufacturers or retailers to recall improperly labeled products if they were labeled prior to the laws effective date of Jan. 1, Although this is not a concern as time goes on, it may account for some inaccurate product labeling for products not updated with the revised allergen labeling. In addition to rules towards the food manufacturers, FALCPA also requires the FDA to conduct facility inspections and issue a report within 18 months of Jan. 1, This report is to ensure that food manufacturers comply with manufacturing regulations to reduce or eliminate cross-contamination with any of the listed allergens. Based on this law there will be a variety of identifiers on package labels to present allergy information; however, FALCPA requires presentation of allergen information to be in one of the two following formats. 1. In the ingredient list, the name of the food source of the allergen is in parenthesis after the common name and may be in bold, for example: a. Ingredients chicken stock, enriched pasta (wheat flour, egg whites, niacin, ferrous sulfate, thiamine mononitrate, riboflavin, folic acid) carrots, modified food starch, flavoring (milk, soy) celery, salt, corn starch, sugar, water 2. near the ingredient list or immediately following the list of ingredients the word, Contains followed by the allergens, for example: b. Ingredients whole corn, vegetable oil (contains one or more of the following: corn, and/or sunflower oil), calcium, guar gum, wheat flour, cinnamon, caramel color, chocolate chips (sugar, chocolate liquor, milk, vanilla), eggs, garlic powder, red and green bell pepper powder. Contains: milk, egg, and wheat ingredients Some manufacturers may also list disclaimers that foods may be unintentionally cross contaminated with May 2011 america s Pharmacist 41

10 major food allergens during manufacturing and processing. These disclaimers may be printed anywhere on the product label but most often are found on the front of the package or under the ingredient list. Clarifications of ingredients may also be listed in the allergen section at the end of the ingredient list. Examples of these include: May contain traces of nuts, soy and wheat Packed in a facility that handles peanuts, milk soy, wheat and egg products Contains: milk and soy, may contain traces of wheat Other labels on food products that are not required but may help identify gluten-free products include: Gluten-Free Manufactured or produced in a gluten-free facility Under FALCPA, the FDA is required to issue a final report on the labeling of gluten-free for manufacturers to define gluten-free and state requirements of a product under that claim. This report was to have been completed by 2008; however, as of 2010, the FDA has not enacted any specific guidelines. Currently, the only published document is a proposed rule for labeling. According to the FDA, the term gluten-free on a label would mean that a food does not contain any of the following: A prohibited grain, including wheat (genus: Triticum), rye (genus: Secale), barley (genus: Hordeum) and cross breed wheat hybrids (ie triticale) A prohibited grain (or derivative) that has not been processed to remove gluten A prohibited grain (or derivative) that has been processed to remove gluten, but still contains 20 parts per million (ppm) gluten 20 ppm gluten (based on reliable technology able to consistently detects gluten levels 20 ppm) Currently, labeling products as gluten-free is voluntary and not a requirement of manufacturers as part of FALCPA. Therefore, the amount of gluten found in items labeled as gluten-free may vary from product to product. Other strategies to verify the amount of possible cross contamination is to buy gluten-free products that contain a gluten-free recognition or certification seal from organization that test for gluten content. The Celiac Sprue Association, (CSA) requires products to test at <5 PPM gluten to qualify for their CSA Seal of Recognition. The Gluten Intolerance Group (GIG) has similar requirements in which a product must test at 10 PPM gluten to receive the GIG gluten-free certification. The FDA is still investigating methods to accurately confirm an estimated safe level of gluten exposure. Table 5 contains a list of CD organizations. Is Complete Avoidance of Oats Necessary? As previously stated, CD patients are advised to avoid oats in addition to wheat, barley, and rye. Oats, however, are not considered one of the prohibited grains by the FDA and have not been identified as a definite cause of CD symptoms. This inconsistency stems from two reasons. First, it is debated whether or not the protein in oats causes an immune reaction in celiac patients as seen with the other grains. Research suggests that patients diagnosed with CD can still tolerate gluten-free oats in amounts as much as 60 grams/day (about 2 ounces or one quarter cup dry steel oats). Second, oats in their natural form do not contain gluten and are classified as the tribe Aveneae. This class of grains is separate from wheat, barley and rye, which are all classified as the tribe Triticeae. However, cross reactivity is still possible. Avoidance of oats is still recommended in patients with CD since an estimated 1 percent to 5 percent of CD patients react to oats with resulting GI symptoms such as bloating and diarrhea. Also, the method of harvesting and processing oats is commonly done in mills that also process wheat, leading to an increased risk of cross contamination. Due to this contamination risk and difficulty identifying this disclaimer on ingredient lists, patients are advised to refrain, unless labels clearly indicate the product is wheat and glutenfree. For patients considering adding oats to their diet, it is recommended they introduce it once they have been on a gluten-free diet to determine if the oat consumption is causing recurrent GI symptoms. Patients choosing to eat oats should ensure they are gluten-free and manufactured in a gluten-free facility. 42 america s Pharmacist May

11 Gluten in Prescription and OTC Medications A survey published in 2001 reported that only about 5 percent of pharmaceutical companies have a policy of producing gluten-free products. However, only a handful of medications actually contain gluten. As is the case with certain food products, identifying gluten in medications and supplements can be difficult. One issue is that, unlike food, few drug products (OTC or prescription) are labeled as being gluten-free. This may be a result of manufacturer s inability to guarantee the gluten-free status of their medications as a result of the raw materials for the inactive ingredients or the excipients being supplied from different companies. Therefore, drug manufacturers claim that they cannot guarantee that the inactive ingredients do not contain gluten or that cross-contamination with non-gluten products has not occurred during processing. In some cases, manufacturers will state that to the best of their knowledge, they are unaware of any gluten containing products but cannot confirm the gluten-free status of the other ingredients being supplied to them. Gluten in medications can result from a variety of inactive ingredient that are obtained from whole grains, grain flour, starch (grain or pregelatinized), dusting powder, and flour. As previously mentioned, FALCPA requires manufacturers to clearly label if a food product contains protein derived from any of listed food allergens. However this law only pertains to food manufacturers and is not a requirement for medication manufacturers of prescription or OTC products. To err on the side of caution, patients are advised to directly verify a product s gluten content with the manufacturer, even if the ingredient list dismisses any gluten content. Helpful resources for patients and pharmacists include websites of organizations that list medications that may or may not include gluten. These organizations include The American Dietetic Association and its National Center for Nutrition and Dietetics Consumer Nutrition Hotline, The National Foundation for Celiac Awareness (NFCA), and the Gluten-free Yellow Pages. Table 5 contains a list of these resources. These resources are helpful in determining gluten content, but directly verifying with the manufacturer is still preferred prior to conveying this information to the patient. Although manufacturers may state certain medications do not contain gluten, other ingredients may be obtained from sources that process gluten products. Upon switching from brand-to-generic or from generic-togeneric, it is important to note that different manufacturers may use different inactive ingredients and excipients, which my contain gluten. Therefore, it is always a good idea to periodically check with manufacturers, especially for chronic medications or if the medication is a switch between brand and generics. Gluten in Medications If a medication does contain gluten or if there is uncertainty, pharmacists should request an alternative medication from the physician where gluten-free status can be verified. Another solution is to consult a compounding pharmacist to have the medication made free of gluten. Refer to Table 4 for the gluten status of different ingredients. General Tips for Patient Counseling Pharmacists have the ability to help patients living with CD through counseling, product recommendations, disease state information, and encouragement of healthy lifestyle habits. As health care professionals, it is important to educate patients on the progression of the disease state (short & long term complications) and how it will directly affect individual organ systems, as well as the the body as a whole. It is key to stress the importance of a lifelong adherence to a completely gluten-free diet. Emphasize that non-adherence is one of the main reasons patients may not experience improvement. Inform patients that although they may not be currently experiencing symptoms, there may be underlying intestinal damage that is occurring while eating gluten. These patients may need more consistent encouragement and counseling to live a healthier lifestyle. In counseling patients with CD it is important to understand the multiple challenges and potential barriers of maintain a gluten-free diet, such as: Hidden gluten/cross contamination Psychological well-being (stress of maintaining the diet) Co-morbid or associated conditions May 2011 america s Pharmacist 43

12 Cost of the food (estimated to be 2 3 times more expensive) Avoidance of activities (restaurants, traveling) Education (available resources, diet, medications) Access to gluten-free foods Label reading (visual impairment, knowledge, time) Ongoing support and education is critical to promote success in achieving and maintaining a gluten-free diet. To assist with the psycho-social aspects of celiac disease, patients are encouraged to join an advocacy or support group Patients coming to the pharmacy seeking information on gluten products (including food and medications) provide an opportunity for pharmacists to educate patients on glutenfree medications (prescription and OTC) as well as supplements. Although few drugs are labeled as gluten-free, package inserts state what inactive ingredients are in medication. If uncertainty of a product s gluten content does arise, refer to any of the stated sources before advising the patient. CD patients are susceptible to vitamin and mineral deficiencies and advised to seek a pharmacist s assistance in proper vitamin supplementation. Patients with classic malabsorption diseases are deficient of fat soluble vitamins (A, D, E, K). As a counseling point, patients should be advised to take vitamins with food to avoid stomach discomfort. Finally, patients should consult their pharmacist or physician about using vitamins with current medications, as well as use with newly prescribed medications. Iron deficiency anemia is another common issue with CD patients, in which supplementing with iron is recommended. Counseling points for iron supplements include taking the tablet with a meal and not taking the tablet within two hours of other medications. The most common adverse effects with iron are upset stomach and constipation. Patients should be instructed to take the iron product while sitting upright and with at least 100 ml of water to avoid esophagitis. CD patients are also at risk for osteoporosis with as many as 40 percent of patients displaying evidence of osteoporosis or osteopenia. A decrease in bone mineral density leads to an increased risk for bone loss, fractures and falls. Although significant improvement is seen within the first year of adhering to a gluten-free diet, patient should have a dual-energy X-ray absorptiometry (DEXA) scan, calcium levels and vitamin D levels checked at the time of diagnosis and after 6 12 months of a gluten-free diet. National Osteoporosis Foundation guidelines (NOF) suggest patients take 1,200 mg of calcium and IU of vitamin D3 daily. Additionally, those with malabsorptive or gastrointestinal disorders should have their serum 25 (OH) D levels measured to ensure it is at within normal limits ( 30 ng/ml or 75 nmol/l) for optimal calcium absorption. Guidelines also note that these patients may need higher doses of vitamin D to achieve this level due to their underlying malabsorption. Patient should only take taking a maximum of 500 mg of elemental calcium per dose for optimal absorption. Calcium Estimating Daily Dietary Calcium Intake (NOF) STEP 1: Estimate calcium intake from calcium-rich foods* Product Servings x Estimated calcium = Calcium serving in mg Milk (8 ounce) x 300 = Yogurt (6 ounce) x 300 = Cheese (1 ounce or 1 cubic inch) x 200 = Fortified foods or juices x 80 to 1,000** = STEP 2: Total from above mg for nondairy sources = total dietary calcium Calcium, in mg * About 75 percent to 80 percent of the calcium consumed in American diets is from dairy products. ** Calcium content of fortified foods varies. 44 america s Pharmacist May

13 carbonate should be taken with meals as an acidic environment is needed for proper absorption. Calcium citrate, on the other hand, does not need to be taken with regard to meals and is ideal for those patients who are also taking PPIs, H2 antagonists, or are achlorhydric. Other important supplements include vitamin B12 and folic acid. Pharmacists can educate patients on how to optimize their gluten-free diet by including vitamin enriched nongrain food sources of iron and B vitamins. As previously mentioned, gluten-free tablet supplements are available for multivitamins and other vitamins/minerals. Due the low fiber content of gluten-free products, patients may experience constipation. This issue can be solved by adding dietary rice bran, or psyllium fiber and methylcellulose supplements, all of which are gluten-free. Pharmacists should be aware that medication properties may change in a patient with celiac disease due to changes in gastrointestinal absorption. This change in pharmacokinetics can lead to alterations in effectiveness or side effects. Opportunities for Community Pharmacists There are numerous opportunities for community pharmacists to help patients with celiac disease. Considering that one in 100 Americans suffer from CD and a reported 15 percent to 25 percent of consumers look for gluten-free products, there is an increasing demand in the gluten-free food market. Fortunately, there has been a significant increase in the supply of amount of new glutenfree products. Research firm Mintel suggests that increase has grown from about 135 products available in 2003 to 832 in Growth of the gluten-free market is projected to reach $2.6 billion by Although there is an increasing supply varying gluten-free products available, the majority of CD patients are claiming it difficult to find good tasting gluten-free products. Drug manufacturers are also noticing this growth trend and are searching for strategies to promote their gluten-free medications. This niche can be transposed to compounding pharmacists, as they have the ability to compound medications guaranteed to be gluten-free. Pharmacists also have the ability to perform a medication therapy management-type service to review medications for their gluten status, and recommend a gluten-free alternative if necessary. The following are additional business strategies to promote the role of pharmacists in the management of CD. 1. Be a source of medication information. Patients may be unaware that several websites are available that list gluten-free medications. Pharmacists can also contact the manufacturer to directly verify the gluten content. Calling the manufacturer may be an advertised service for those patients with CD to ensure their list of medications are gluten-free. If any of the medications contain gluten, the prescriber can be contacted and alternative equivalent can be requested or gluten-free alternative can be compounded. 2. Carry OTC products that are known to be gluten-free. These can be identified through online resources listed in Table 5. Pharmacists can also designate a section of the pharmacy for CD patients to include vitamins and supplements (discussed under: General Tips for Patient Counseling). If space is limited, gluten-free products can be labeled differently, to identify them as products safe for celiac disease patients, while being shelved with other products. 3. Carry a line of gluten-free food products. Gluten-free products have become increasingly available, and may stand out as a unique item if your pharmacy stocks other food products. This gives patients the opportunity to shop for gluten-free products while filling their prescription and avoid making multiple trips for food and medications. Once products are available, provide a well-marked section for gluten-free foods or an easy way for the products to be identified in the pharmacy. Consider advertising with signs in the window or placing items near the front of the store. Keep in mind some grocers also offer samples of products to taste as this can vary significantly between products and manufacturers. When selecting products for the pharmacy, consider the demographics of the patient population especially due to the high cost of the products and also the types of food that people typically come into the pharmacy to buy. 4. Stock literature and resources on CD in the pharmacy and by the prescription counter. Resources may include May 2011 america s Pharmacist 45