Circa 2005
Celiac disease (CD), also called celiac sprue, nontropical sprue and gluten-sensitive enteropathy, is an autoimmune disorder, a condition in which the immune system mistakenly identifies part of the body as a foreign object and mounts an attack against it. For genetically susceptible individuals who develop CD, the ingestion of gluten, a component of many grain products, leads to damage of the lining of the small intestine. Until recently, CD was considered a rare disease, but studies now suggest that it may affect one in every 130 to 300 people in the United States.
Gluten is a general term for the class of water-insoluble proteins found in various grains; a subtype of gluten molecules called prolamines has been identified as the trigger for CD. In individuals with CD, ingestion of the prolamines in wheat, barley and rye—gliadin, hordein and secalin, respectively—sets off an inappropriate immune response that causes inflammation of the small intestine. The mucous membrane that lines the small intestine normally contains many protruding finger-like structures called villi, which increase the surface area for absorption of nutrients. The inflammation in CD often leads to atrophy or flattening of the villi, thereby diminishing absorptive capability.
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DIAGNOSIS AND TREATMENT
The diagnosis of CD is often difficult and prolonged, and misdiagnoses are common. Originally described as an early childhood gastrointestinal disorder that appeared with the introduction of gluten into the diet, CD is now viewed as a condition that can occur at any age, often with variable manifestations and the involvement of multiple organ systems.
All testing for CD must be conducted while a person’s diet still contains gluten, to capture the immune process in action. Blood testing is usually the first step. The two best available blood tests—IgA antihuman tissue transglutaminase (tTG) and IgA endomysial antibody immunofluorescence (EMA)—seem equally accurate and are widely used. Biopsy of the small intestine typically follows positive blood test results. If atrophy of the villi is noted on biopsy, a presumptive diagnosis of CD is made. The diagnosis is confirmed if symptoms resolve with a gluten-free diet.
For people whose symptoms are suggestive of CD but for whom diagnostic testing is not definitive, testing for genetic markers (specifically, human leukocyte antigens [HLAs] DQ2 and DQ8) may be used. Because more than 97 percent of people with CD have one or both markers, someone negative for both DQ2 and DQ8 is unlikely to have CD.
Some children and adults with CD have classic gastrointestinal manifestations, such as inability to grow and thrive; diarrhea; vomiting; constipation; weight loss; and abdominal pain, distension and bloating. Others present with extra-intestinal manifestations, including delayed puberty; infertility; decreased bone mass or osteoporosis; vitamin deficiencies; under-developed dental enamel; depression; migraine headaches; and nerve problems such as pain, tingling and numbness in the hands and feet. Dermatitis herpetiformis (DH), a skin manifestation of CD, can at times be the only presenting symptom. DH typically occurs bilaterally on the knees, elbows and buttocks as a blistering rash that is intensely itchy.
Two asymptomatic forms of CD—silent and latent—are now also recognized. Silent CD, defined by positive biopsy and positive blood tests, is usually detected when an endoscopy or biopsy is performed for an unrelated reason. Latent CD is defined by positive blood tests but negative biopsy; active symptoms of CD and/or atrophy of intestinal villi may develop at a later time.
People diagnosed with CD should undergo bone density screening and be evaluated and treated for vitamin and mineral deficiencies.
At this time, the only known treatment for CD is strict adherence to a life-long gluten-free diet. With dietary compliance, the small intestine typically heals and health improves; however, the ingestion of even small amounts of gluten may result in the recurrence of symptoms and/or atrophy of the villi.
People with CD should be periodically assessed for dietary compliance with repeat blood tests. Persistence of positive blood test results may represent unintended gluten ingestion or lack of strict adherence to the gluten-free diet and needs to be addressed.
THE DOS AND DON’TS OF A GLUTEN-FREE DIET
“The gluten-free diet is very complex to the newly diagnosed, but with time and attention it becomes second nature,” says Melinda Dennis, a registered dietitian who has CD. “I believe it is important for a patient with celiac disease to be educated about the diet by an experienced professional as soon as possible after diagnosis to avoid the likelihood of obtaining misinformation and to receive important nutrition information related to the disease.”
Dennis provides dietary counsel to about 300 patients with CD at Beth Israel Deaconess Medical Center and is the nutrition coordinator of the hospital’s new Celiac Center. She is also founder and owner of Delete the Wheat, a nutrition consulting service in the Boston area. Dennis offers one-on-one gluten-free shopping tours and home visits for those following the gluten-free diet and is also available for lectures and long-distance consults.
Dennis’ initial session with a newly diagnosed individual with CD begins with a general nutrition assessment, which includes a discussion of weight and diet history, followed by an introduction to the complexities of the gluten-free diet. Identifying sources of hidden gluten, preventing cross contamination, reading ingredients labels and shopping for safe and appropriate foods are thoroughly reviewed.
Understanding which grains, flours and starches are toxic and which are not is paramount. “All forms of wheat, rye and barley—and their derivatives—must be strictly avoided. Although oats are inherently gluten-free, it is difficult to find pure oats that have not been contaminated with gluten-containing grains during harvesting or processing,” Dennis says.
Gluten-containing products like wheat bread and wheat germ are high in dietary fiber and are often enriched with vitamins and minerals; not so for many of the grains available to individuals with CD. To increase fiber intake, Dennis suggests choosing products such as brown rice, wild rice, buckwheat groats and garbanzo flour, and adding flax seed to hot cereal and yogurt. Amaranth, quinoa, millet and teff, which are more likely to be enriched with necessary nutrients than frequently suggested safe products like potato flour or tapioca, should also be incorporated into a glutenfree diet, she says.
Dennis encourages her patients to shop the perimeter of the grocery store to obtain the basics of a gluten-free diet: plain meats, fish, poultry, eggs, milk, cheese, fruits and vegetables. Once people with CD become proficient at label reading, more of the canned and packaged foods become available to them. Gluten may also be present in medications (over-the-counter and prescription) and vitamin/mineral supplements, Dennis cautions, so individuals with CD should always verify ingredients with a pharmacy and/or manufacturer.
Cross-contamination—at home and while shopping or dining out—is a serious issue for all people with CD because of the risk posed by accidental gluten ingestion. For the home, Dennis suggests implementing the following safe kitchen guidelines: isolate all gluten-free foods; clean cutting boards, microwave walls and countertops frequently; avoid double-dipping; store condiments in squeeze bottles; segregate cooking utensils that could potentially trap gluten (e.g., colanders); and use a separate toaster for gluten-free products. Furthermore, people with CD who prepare gluten-containing food for others should wash their hands after completing the task, and shopping from bulk bins should be avoided.
Dennis cautions that when dining out it is important to ask the right questions about food preparation. Is rice bread being toasted in a toaster that has been used for whole wheat bread? Has the chicken been dusted with flour before cooking? Is gluten-free food being prepared in the same fryer in which gluten-containing foods have been prepared?
Label reading is an important topic in nutrition counseling and particularly challenging for patients with CD. “Many everyday products— seasonings, canned soups and soy sauce—may contain gluten, so it is critical that patients check the ingredients list before purchasing any product. Unfortunately, labels and ingredients may change at any time and without notice, which is a huge problem for people with this condition,” says Dennis.
But there is more to it,because patients with CD must also worry about hidden gluten lurking in thickeners, emulsifiers, stabilizers and flavorings. Ingredients like modified food starch, hydrolyzed vegetable protein, hydrolyzed plant protein and textured vegetable protein can be derived from several sources, including wheat, and thus may contain gluten.
Because the gluten-free diet is one of the most difficult to accept and manage, Dennis encourages her patients to seek assistance from established celiac support groups. Such groups, she says, offer updated product information, resource materials, and invaluable social and emotional support to both patients and providers.
Despite the challenges a gluten-free diet presents, Dennis nonetheless believes that CD is a manageable condition. “People who have a positive attitude, accept their condition and adhere strictly to diet therapy can lead healthy and fulfilling lives,” Dennis says. “The key to success is having a clear understanding of all aspects of gluten-free living and sticking to the program.”
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LONG-TERM COMPLICATIONS OF CELIAC DISEASE
The complications of CD occur primarily in adults with a long history of the disease. Although dietary compliance reduces the risk of complications, some individuals develop refractory CD (i.e., failure to respond to the gluten-free diet). Refractory CD may be associated with ulcerative jejunitis (denuding of large areas of the lining of the small intestine) or early intestinal lymphoma.
Research has shown that people diagnosed with CD during adulthood have an increased risk of two types of cancer: enteropathy-associated T-cell lymphoma (EATL), a subtype of non-Hodgkin’s lymphoma, and adenocarcinoma of the small intestine. Furthermore, many people with CD have other coexisting autoimmune disorders, such as thyroid disease, diabetes, multiple sclerosis and rheumatoid arthritis. The death rate from all causes is two times higher in individuals with clinically diagnosed CD than in control populations.
THE PSYCHOSOCIAL CHALLENGES OF LIVING WITH CELIAC DISEASE
“I understand what others are going through because of my long history with celiac disease,” says Lauren Komack, a clinical social worker who was initially diagnosed with the disease in 1946. “Since my rediagnosis 18 years ago, I’ve developed a special interest in speaking with individuals and families about its psychological and emotional aspects.”
In presentations to celiac support groups, Komack stresses that CD can be a significant presence, but she says it is also important to remember that the disease is only one component in the lives of those affected and its effect changes over time. She observes that each individual brings a unique perspective to the process, with emotions spanning a wide spectrum from initial denial and fear to subsequent mastery and triumph.
Komack explains that a diagnosis of CD often puts a strain on relationships because advocating for a glutenfree diet can be very taxing. “I’ve heard some people say they stop accepting social invitations because it is too difficult to talk about their needs. Others tell me friends and family minimize the importance of the diet or do not understand it sufficiently to make accommodations.”
Solving such interpersonal problems involves give and take, so Komack advises her clients to have patience and a willingness to educate. “I tell people with celiac disease that the process may begin with an offer to bring their own food to a dinner party to illustrate the importance of the diet. And who knows? Over time, you might find the host segregating food to avoid accidents and cross-contamination for a friend with celiac disease.”
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IS AT1001 THE ANSWER?
Alessio Fasano, MD, was recently appointed director of the new Mucosal Biology Research Center at the University of Maryland, of which the university’s Center for Celiac Research (CFCR) is an integral part. Fasano, who also directs CFCR, reports that a multidisciplinary group of researchers at the two entities is collaborating to advance knowledge about autoimmunity within the context of CD.
“Our team is convinced that celiac disease is the best disease model for studying basic autoimmunity because we have luxuries with CD that we don’t have with other diseases,” Fasano says. “We know some of the genes involved; we know tissue transglutaminase is the antigen that is the object of the autoimmune response [the protein the body mistakes as foreign]; we know the small intestine is the primary target organ; and most importantly, we know the environmental trigger that leads to the autoimmune process is gluten.”
Fasano explains that under normal circumstances, large molecules like gluten are prevented from entering the body by a formidable barrier that covers the entire intestine. The barrier is a single layer of cells, and the spaces between the cells are tight junctions, dynamic structures that can be conceptualized as gates that open and close.
But what is the key, and when does the key open the gate, and why?
A few years ago, Fasano’s team discovered the key— the protein zonulin, which regulates the opening and closing of the gates and controls gut permeability.
“Around the same time, we also determined that most of the autoimmune diseases are characterized by an extremely permeable intestinal wall and that individuals [with impaired immune function], particularly those with diabetes and CD, have abnormally high zonulin levels,” Fasano explains. “Our next task, of course, was to find a way to inhibit the zonulin.”
It didn’t take long for the Fasano team to find an inhibitor and to develop an animal model for testing. Using diabetes-prone rats, the researchers evaluated the effectiveness of the zonulin peptide inhibitor AT1001. The rats were randomized to two groups—one group that received the inhibitor in their drinking water on a daily basis and an untreated control group. Eighty percent of the untreated rats developed diabetes, compared with only 26 percent of the treated rats.
“We know these animals developed diabetes because they leak in their gut, and they leak in their gut because of out-of-control zonulin,” Fasano says. “If you stop the leak by preventing the unusually high level of zonulin from interacting with its target receptor on intestinal cells, you will prevent diabetes.”
The plan now is to test the inhibitor in humans, Fasano states, specifically in individuals with CD. “You would take a pill that contains the inhibitor and 15 minutes later eat some pizza or a Big Mac. The gluten in the food would cause a huge amount of zonulin to be released, but by the time it reached the target, the target would be blocked, and the intestine would not leak. The gluten would remain in the intestine until completely digested and would not have access to the immune system.”
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RESEARCHERS SEARCH FOR GENES THAT CAUSE CELIAC DISEASE
Susan Neuhausen, PhD, and her colleagues at the University of California-Irvine are studying families in which two or more members have been formally diagnosed with CD or dermatitis herpetiformis (DH). Their goal is to identify genes that may cause CD other than the human leukocyte antigen (HLA) genes.
“Many people think that all you need for celiac disease is the high-risk HLA type, DQ2, but that’s not true. In most cases, it appears the DQ2 type is necessary, but not sufficient,” Neuhausen says. “Based on several studies, HLA accounts for less than half of the risk for celiac disease, so the goal of our study is to find the other genes that cause the disease.”
To be eligible for the study, families must have at least two members, excluding parent-child pairs, who have been diagnosed with CD (by positive small intestine biopsy or blood testing) or DH (by positive skin biopsy).
Once enrolled in the study, individuals are asked to complete questionnaires about medical history, family history and diet and to provide blood samples for blood testing and genetic analysis. About 160 families are currently participating, some with two affected siblings and others with up to 12 affected family members.
Neuhausen says that in families where two siblings are affected, approximately 20 percent of first-degree relatives and 10 to 20 percent of more distant relatives test positive on blood tests for CD. Furthermore, an initial search to identify non-HLA genes has turned up some regions of interest that warrant further investigation, and Neuhausen says additional families will be studied to confirm and refine the location of the genes.
“Once genes for celiac disease are identified, we will be able to better understand how the disease occurs and progresses, as well as its associated complications and other diseases,” she explains. “This knowledge could eventually lead to the development of preventative strategies and therapies directed at molecular defect(s), thus eliminating severe diet restrictions and medical complications] from the disease. Development of a gene-based diagnostic test for celiac disease would allow for a presymptomatic test for celiac disease, as well a test that is informative even for those on a glutenfree diet.”
The researchers expect to enroll about 2,100 participants at UC-Irvine and 300 participants at a collaborating center in Israel through 2006. The study is being funded by the National Institutes of Health.
by Kathleen A. Wildasin
Kathleen Wildason, who herself lives with celiac disease, is a freelance medical writer in Lexington, Kentucky.
For more information about the UC-Irvine study, contact study manager Maryam Mousavi at 866.356.9962 or mmousavi@uci.edu
Celiac Sprue Association of the United States of America, Inc. 402.558.0600 csaceliacs.org
Celiac Disease Foundation 818.990.2354 celiac.org
Gluten Intolerance Group 206.246.6652 gluten.net
Delete the Wheat, 617.851.8643, Melinda_Dennis@hotmail.com
Celiac Community Encouraged by New Food Allergen Labeling Law
One of the greatest challenges of a gluten-free diet is avoiding hidden sources of gluten. Many ingredients labels do not state clearly whether gluten is present in a product, thus making it difficult for individuals with celiac disease to choose safe foods. Furthermore, although products labeled gluten-free are considered safe for those with the disease, the term has not yet been officially defined and its use is not regulated in the United States.
In March 2003, Alessio Fasano, MD, director of the Mucosal Biology Research Center and the Center for Celiac Research at the University of Maryland, convened a meeting of members of the celiac community to address the concerns of all people with celiac disease, including the need for understandable food labeling. Shortly after the meeting, the American Celiac Task Force (ACTF) was formed for the purpose of lobbying Congress to enact food labeling legislation.
Sixteen months of hard work paid off, and on August 2, 2004, the Food Allergen Labeling and Consumer Protection Act (FALCPA) was signed into law. The act mandates the listing on ingredients labels of the top eight food allergens (milk, eggs, peanuts, tree nuts, fish, crustacean shellfish, soybeans and wheat), beginning January 1, 2006. Labels on institutional-sized food packaging, vitamins and dietary supplements must also conform to the new regulations.
Furthermore, FALCPA mandates that proposed rules for definition of the term gluten-free and permission to use it on food labels be issued no later than August 2, 2006; final rules must be issued by August 2, 2008.
“It is estimated that about 90 percent of the labeling problems for those with celiac disease arise from wheat or wheat derivatives, so having wheat listed on the label is a major first step,” says Andrea Levario, JD, co-chairperson of the ACTF. “As the number of individuals with the disease continues to rise, hopefully food manufacturers will take the initiative and list the other problem grains as well.”
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How Children with Celiac Disease Manage at School
“The school’s understanding of celiac disease and the gluten-free diet is vital because it gives me peace of mind knowing that my daughter is healthy and safe while she is away from me,” says Pat Vlamis, mother of a first-grader with celiac disease. “When Mary started school, I spoke with her teachers and the food service to help them understand her condition.”
Vlamis says that the teachers have been “accommodating and wonderful” by informing her in advance of food-related projects and potentially problematic events. They also allow her to keep gluten-free goodies in the classroom for unplanned treats and gluten-free cupcakes in the freezer for birthday and school parties.
“At first, the food service believed that because celiac disease wasn’t life-threatening—like a peanut allergy— there wasn’t much they were obligated to do. After several meetings, however, they are trying to be more helpful, and we’ve finally worked out a few menus that Mary can eat from the cafeteria,” Vlamis says.
The staff has been trained in the preparation of Mary’s food, so cross contamination is not an issue. “Mary’s rice is steamed separately and her hamburger and fries are made in the oven. Arrangements have also been made for Mary to have gluten-free pizza that will come in its own tin plate,” Vlamis explains.
Because no other children in the class have celiac disease, Vlamis read an age-appropriate pamphlet to them to help explain Mary’s condition. “After I read ‘The Trouble That Jack Had,’ the kids had lots of questions, and then we made apple pies—Mary’s first with a gluten-free crust, and then pies with wheat crusts. The kids now understand why Mary has special foods.”
An added benefit of educating the other children about celiac disease is that they now “look out for Mary and are concerned that she is eating safe foods,” Vlamis says.
As a parent of adult children, Susan Stritar relates, “We thought it would be tougher when our two sons went away to college, but both schools could not have been more cooperative. Both sons learned to live quite easily with celiac disease, even though they had two completely different situations.”
The key to success was planning ahead by meeting with appropriate campus personnel and providing her sons with a list of gluten-free products.
“Our oldest son Joe, now graduated, ate all of his meals in one dining hall,” Stritar describes. “He had a close working relationship with the chefs, and although the selection was limited and sometimes boring, there was always something he could eat.”
Stritar’s youngest son currently lives in a fraternity where the students cook. It works well, Stritar says, because everyone has been educated about celiac disease. “Jon checks in at dinnertime to see if he can have what is being served. If not, he is often able to make changes, like having the meat plain, without the sauce they are using. At times, there is no safe choice, but that is rare,” she says.
The biggest difficulty for both boys is taking the time to check the ingredients of all foods. “They would rather just eat like everyone else, without that effort,” Stritar says. “Oh, and of course, college without beer and pizza is difficult because it is so much a part of life there.”
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Living with Celiac Disease: How times have changed
I t would be hard to find two people more experienced in the art of gluten-free living than celiac leaders Janet Rinehart and Jane Trevett.
Rinehart was given a diagnosis of probable celiac disease in 1945 after failure to thrive (a problem gaining weight, growing and maturing) as an infant, and was definitively diagnosed by biopsy when symptoms resurfaced in the 1980s. Trevett’s sure and swift biopsy-confirmed diagnosis came after a twoweek hospitalization for weight loss and diarrhea in 1965. Both women say that childbirth was the likely trigger of their respective cases of full-blown celiac disease.
“During the World War II era, a banana diet was sometimes used to treat children with celiac disease. Some of the banana babies continued to be sick, but somehow, strangely, the prescribed regimen of nine bananas a day for several years caused my symptoms to abate, and I went into remission for more than 30 years,” Rinehart says. “The digestive problems returned after my last pregnancy and developed slowly into celiac disease over a 10-year period.”
After being rediagnosed with celiac disease as an adult, Rinehart managed the gluten-free diet on her own for about nine months, but she says patient resources were limited and it was difficult. “There were two major national support groups, a couple of gluten-free food manufacturers and three gluten-free cookbooks, all written by the same woman. I finally decided to reach out and attend a meeting of the Celiac Sprue Association/USA (CSA/USA), which turned out to be a life-changing event.”
Rinehart’s adventure began at the conference registration table, where she met two other celiacs from her hometown of Houston. The women bonded throughout the conference and were surprised when the executive director of CSA asked if they would be interested in starting a local support group.
“Not appreciating the amount of work that would be involved, we signed on, and the Houston Celiac Support Group was born,” Rinehart recalls. “I was the one with the computer, so I naturally became the membership record keeper. Our initial enrollment of ten members in 1989 has grown to more than 600 strong and counting.”
Rinehart’s role with the Houston Celiac Support Group has evolved over the years, and now as chairman she is busier than ever. In addition to writing the quarterly newsletter, Rinehart consults on the phone with each new member, visits celiacs in the hospital and meets newbies at specialty markets to point out appropriate gluten-free products and find acceptable substitutions.
“Going gluten-free is a big challenge,” Rinehart says, “and the experiences I have had helping others learn about the diet have been extremely gratifying.”
Trevett, similarly, has shared in expanding the community of support available for people with celiac disease. “Being diagnosed with celiac disease 40 years ago was a lonely experience,” she relates. “The CSA/USA was not founded until 1978, there were no local support groups, and the gluten-free food available at health stores was not worth eating. Only my close friends and family really understood my condition.”
Nonetheless, Trevett says she is grateful for the relative ease with which her diagnosis was made and that she has a disease that is 100 percent treatable with strict dietary compliance.
Trevett describes her initial diet of plain meat, potatoes, vegetables, rice and fruit as standard fare and not unpleasant. A lone recipe for corn muffins satisfied her sweet tooth, and she remembers doing well without a lot of baked goods. “I started feeling well immediately after going on the diet. My weight continued to improve over time, and unfortunately, I have had no trouble gaining weight ever since.”
Fifteen years after her diagnosis, Trevett attended a celiac support group meeting in Massachusetts and met, for the first time, another person with celiac disease. She also encountered children with the disease and grew to appreciate the difficulty of dietary compliance in this age group, as well as the critical role played by parents in disease management.
In 1996, Trevett cofounded the Greater New Haven Celiac Group to help others dealing with the disease. As a leader in the celiac community, she believes in the effectiveness of celiac support groups and encourages all celiacs to become members. The short-term benefits of these groups are to educate, encourage and support new celiacs in strict adherence to the gluten-free lifestyle; the long-term effect is to greater celiac awareness among medical, school and restaurant personnel.
“I am excited and optimistic about the future for celiacs,” Trevett states, “and I hope that as researchers and physicians learn more about the disease, the length of time typically required for its diagnosis will be improved.”
