A.D.A.M. Medical Encyclopedia.

Celiac disease - sprue

Sprue; Nontropical sprue; Gluten intolerance; Gluten-sensitive enteropathy
Last reviewed: January 20, 2010.

1.Green PH, Cellier C. Celiac disease. N Engl J Med. 2007;357:17311743. 2.Semrad CE, Powell DW. Approach to the patient with diarrhea and malabsorption. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 143.
Review Date: 1/20/2010. Reviewed by: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine; and George F. Longstreth, MD, Department of Gastroenterology, Kaiser Permanente Medical Care Program, San Diego, California. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M., Disclaimer Copyright 2012, A.D.A.M., Inc. Celiac disease is a condition that damages the lining of the small intestine and prevents it from absorbing parts of food that are important for staying healthy. The damage is due to a reaction to eating gluten, which is found in wheat, barley, rye, and possibly oats.

Causes, incidence, and risk factors

The exact cause of celiac disease is unknown. The lining of the intestines contains areas called villi, which help absorb nutrients. When people with celiac disease eat foods or use products that contain gluten, their immune system reacts by damaging these villi. This damage affects the ability to absorb nutrients properly. A person becomes malnourished, no matter how much food he or she eats. The disease can develop at any point in life, from infancy to late adulthood. People who have a family member with celiac disease are at greater risk

for developing the disease. The disorder is most common in Caucasians and persons of European ancestry. Women are affected more often than men. People with celiac disease are more likely to have: 3.Autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus, and Sjogren syndrome 4.Addison's disease 5.Down syndrome 6.Intestinal cancer 7.Intestinal lymphoma 8.Lactose intolerance 9.Thyroid disease 10. Type 1 diabetes

Symptoms
The symptoms of celiac disease can be different from person to person. This is part of the reason why the diagnosis is not always made right away. For example, one person may have constipation, a second may have diarrhea, and a third may have no problem with stools. Gastrointestinal symptoms include: Abdominal pain, bloating, gas, or indigestion Constipation Decreased appetite (may also be increased or unchanged) Diarrhea, either constant or off and on Lactose intolerance (common when the person is diagnosed, usually goes away after treatment) Nausea and vomiting Stools that float, are foul smelling, bloody, or fatty Unexplained weight loss (although people can be overweight or of normal weight) Because the intestines do not absorb many important vitamins, minerals,

and other parts of food, the following symptoms may start over time: Bruising easily Depression or anxiety Fatigue Growth delay in children Hair loss Itchy skin (dermatitis herpetiformis) Missed menstrual periods Mouth ulcers Muscle cramps and joint pain Nosebleeds Seizures Tingling or numbness in the hands or feet Unexplained short height Children with celiac disease may have: Defects in the tooth enamel and changes in tooth color Delayed puberty Diarrhea, constipation, fatty or foul-smelling stools, nausea, or vomiting Irritable and fussy behavior Poor weight gain Slowed growth and shorter than normal height for their age

Signs and tests

Albumin (may be low) Alkaline phosphatase (high level may be a sign of bone loss) Clotting factor abnormalities Cholesterol (may be low) Complete blood count (CBC - test for anemia)

 Liver enzymes (transaminases) Prothrombin time Blood tests can detect several special antibodies, called antitissue transglutaminase antibodies (tTGA) or anti-endomysium antibodies (EMA). The health care provider will order these antibody tests if celiac disease is suspected. If the tests are positive, upper endoscopy is usually performed to sample a piece of tissue (biopsy) from the first part of the small intestine (duodenum). The biopsy may show a flattening of the villi in the parts of the intestine below the duodenum. Genetic testing of the blood is also available to help determine who may be at risk for celiac disease. A follow-up biopsy or blood test may be ordered several months after the diagnosis and treatment. These tests evaluate your response to treatment. Normal results mean that you have responded to treatment, which confirms the diagnosis. However, this does not mean that the disease has been cured.

Treatment
Celiac disease cannot be cured. However, your symptoms will go away and the villi in the lining of the intestines will heal if you follow a lifelong gluten-free diet. Do not eat foods, beverages, and medications that contain wheat, barley, rye, and possibly oats. You must read food and medication labels carefully to look for hidden sources of these grains and ingredients related to them. Because wheat and barley grains are common in the American diet, sticking with this diet is challenging. With education and planning, you will heal. You should NOT begin the gluten-free diet before you are diagnosed. Starting the diet will affect testing for the disease. The health care provider may prescribe vitamin and mineral supplements to correct nutritional deficiencies. Occasionally, corticosteroids (such as prednisone) may also be prescribed for short-term use or if you have sprue that does not respond to treatment. Following a well-balanced, gluten-free diet is generally the only treatment you need to stay well. When you are diagnosed, get help from a registered dietitian who specializes in celiac disease and the gluten-free diet. A support group may also help you cope with the disease and diet.

Support Groups
For additional information and support, see the organizations listed in celiac disease resources.

Expectations (prognosis)
Following a gluten-free diet heals the damage to the intestines and prevents further damage. This healing most often occurs within 3 - 6 months in children, but it may take 2 - 3 years in adults. Rarely, long-term damage will be done to the lining of the intestines before the diagnosis is made. Some problems caused by celiac disease may not improve, such as a shorter than expected height and damage to the teeth.

Complications
You must carefully continue to follow the gluten-free diet. When untreated, the disease can cause life-threatening complications. Delaying diagnosis or not following the diet puts you at risk for related conditions such as: Autoimmune disorders Bone disease (osteoporosis, kyphoscoliosis, fractures) Certain types of intestinal cancer Low blood count (anemia) Low blood sugar (hypoglycemia) Infertility or repeated miscarriage Liver disease

Calling your health care provider

Call your health care provider if you have symptoms of celiac disease.

Prevention
Because the exact cause is unknown, there is no known way to prevent the development of celiac disease. However, being aware of the risk factors (such as having a family member with the disorder) may increase your chances of early diagnosis, treatment, and a long, healthy life.

http://digestive.niddk.nih.gov/ddiseases/pubs/celiac/

What is celiac disease?

Celiac disease is a digestive disease that damages the small intestine and interferes with absorption of nutrients from food. People who have celiac disease cannot tolerate gluten, a protein in wheat, rye, and barley. Gluten is found mainly in foods but may also be found in everyday products such as medicines, vitamins, and lip balms.

The small intestine is shaded

above.

When people with celiac disease eat foods or use products containing gluten, their immune system responds by damaging or destroying villithe tiny, fingerlike protrusions lining the small intestine. Villi normally allow nutrients from food to be absorbed through the walls of the small intestine into the bloodstream. Without healthy villi, a person becomes malnourished, no matter how much food one eats.

 Villi on the lining

of the small intestine help absorb nutrients.

Celiac disease is both a disease of malabsorptionmeaning nutrients are not absorbed properlyand an abnormal immune reaction to gluten. Celiac disease is also known as celiac sprue, nontropical sprue, and gluten-sensitive enteropathy. Celiac disease is genetic, meaning it runs in families. Sometimes the disease is triggeredor becomes active for the first timeafter surgery, pregnancy, childbirth, viral infection, or severe emotional stress. [Top]

What are the symptoms of celiac disease?

Symptoms of celiac disease vary from person to person. Symptoms may occur in the digestive system or in other parts of the body. Digestive symptoms are more common in infants and young children and may include 11. abdominal bloating and pain 12. chronic diarrhea 13. vomiting 14. constipation 15. pale, foul-smelling, or fatty stool 16. weight loss Irritability is another common symptom in children. Malabsorption of nutrients during the years when nutrition is critical to a child's normal growth and development can result in other problems such as failure to thrive in infants, delayed growth and short stature, delayed puberty, and dental enamel defects of the permanent teeth. Adults are less likely to have digestive symptoms and may instead have one or more of the following: unexplained iron-deficiency anemia fatigue bone or joint pain arthritis

 bone loss or osteoporosis depression or anxiety tingling numbness in the hands and feet seizures missed menstrual periods infertility or recurrent miscarriage canker sores inside the mouth an itchy skin rash called dermatitis herpetiformis People with celiac disease may have no symptoms but can still develop complications of the disease over time. Long-term complications include malnutritionwhich can lead to anemia, osteoporosis, and miscarriage, among other problemsliver diseases, and cancers of the intestine. [Top]

Why are celiac disease symptoms so varied?

Researchers are studying the reasons celiac disease affects people differently. The length of time a person was breastfed, the age a person started eating gluten-containing foods, and the amount of gluten-containing foods one eats are three factors thought to play a role in when and how celiac disease appears. Some studies have shown, for example, that the longer a person was breastfed, the later the symptoms of celiac disease appear. Symptoms also vary depending on a person's age and the degree of damage to the small intestine. Many adults have the disease for a decade or more before they are diagnosed. The longer a person goes undiagnosed and untreated, the greater the chance of developing longterm complications. [Top]

What other health problems do people with celiac disease have?

People with celiac disease tend to have other diseases in which the immune system attacks the body's healthy cells and tissues. The connection between celiac disease and these diseases may be genetic. They include type 1 diabetes autoimmune thyroid disease autoimmune liver disease rheumatoid arthritis Addison's disease, a condition in which the glands that produce critical hormones are damaged Sjgren's syndrome, a condition in which the glands that produce tears and saliva are destroyed [Top]

How common is celiac disease?

Celiac disease affects people in all parts of the world. Originally thought to be a rare childhood syndrome, celiac disease is now known to be a common genetic disorder. More than 2 million people in the United States have the disease, or about 1 in 133 people.1 Among people who have a first-degree relativea parent, sibling, or childdiagnosed with celiac disease, as many as 1 in 22 people may have the disease.2 Celiac disease is also more common among people with other genetic disorders including Down syndrome and Turner syndrome, a condition that affects girls' development.
1

Fasano A, Berti I, Gerarduzzi T, et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States. Archives of Internal Medicine. 2003;163(3):268292. 2 Ibid. [Top]

How is celiac disease diagnosed?

Recognizing celiac disease can be difficult because some of its symptoms are similar to those of other diseases. Celiac disease can be confused with irritable bowel syndrome, iron-deficiency anemia caused by menstrual blood loss, inflammatory bowel disease, diverticulitis, intestinal infections, and chronic fatigue syndrome. As a result, celiac disease has long been underdiagnosed or misdiagnosed. As doctors become more aware of the many varied symptoms of the disease and reliable blood tests become more available, diagnosis rates are increasing. Blood Tests People with celiac disease have higher than normal levels of certain autoantibodiesproteins that react against the body's own cells or tissuesin their blood. To diagnose celiac disease, doctors will test blood for high levels of anti-tissue transglutaminase antibodies (tTGA) or antiendomysium antibodies (EMA). If test results are negative but celiac disease is still suspected, additional blood tests may be needed. Before being tested, one should continue to eat a diet that includes foods with gluten, such as breads and pastas. If a person stops eating foods with gluten before being tested, the results may be negative for celiac disease even if the disease is present. Intestinal Biopsy If blood tests and symptoms suggest celiac disease, a biopsy of the small intestine is performed to confirm the diagnosis. During the biopsy, the doctor removes tiny pieces of tissue from the small intestine to check for damage to the villi. To obtain the tissue sample, the doctor eases a long, thin tube called an endoscope through the patient's mouth and stomach into the small intestine. The doctor then takes the samples using instruments passed through the endoscope.

Dermatitis Herpetiformis Dermatitis herpetiformis (DH) is an intensely itchy, blistering skin rash that affects 15 to 25 percent of people with celiac disease.3 The rash usually occurs on the elbows, knees, and buttocks. Most people with DH have no digestive symptoms of celiac disease. DH is diagnosed through blood tests and a skin biopsy. If the antibody tests are positive and the skin biopsy has the typical findings of DH, patients do not need to have an intestinal biopsy. Both the skin disease and the intestinal disease respond to a gluten-free diet and recur if gluten is added back into the diet. The rash symptoms can be controlled with antibiotics such as dapsone. Because dapsone does not treat the intestinal condition, people with DH must maintain a gluten-free diet. Screening Screening for celiac disease means testing for the presence of autoantibodies in the blood in people without symptoms. Americans are not routinely screened for celiac disease. However, because celiac disease is hereditary, family members of a person with the disease may wish to be tested. Four to 12 percent of an affected person's first-degree relatives will also have the disease.4
3

Rodrigo L. Celiac disease. World Journal of Gastroenterology. 2006;12(41):65856593. 4 Ibid. [Top]

How is celiac disease treated?

The only treatment for celiac disease is a gluten-free diet. Doctors may ask a newly diagnosed person to work with a dietitian on a gluten-free diet plan. A dietitian is a health care professional who specializes in food and nutrition. Someone with celiac disease can learn from a dietitian how to read ingredient lists and identify foods that contain gluten in order to make informed decisions at the grocery store and when eating out. For most people, following this diet will stop symptoms, heal existing intestinal damage, and prevent further damage. Improvement begins within days of starting the diet. The small intestine usually heals in 3 to 6 months in children but may take several years in adults. A healed intestine means a person now has villi that can absorb nutrients from food into the bloodstream. To stay well, people with celiac disease must avoid gluten for the rest of their lives. Eating even a small amount of gluten can damage the small intestine. The damage will occur in anyone with the disease, including people without noticeable symptoms. Depending on a person's age at diagnosis, some problems will not improve, such as short stature and dental enamel defects. Some people with celiac disease show no improvement on the gluten-free

diet. The most common reason for poor response to the diet is that small amounts of gluten are still being consumed. Hidden sources of gluten include additives such as modified food starch, preservatives, and stabilizers made with wheat. And because many corn and rice products are produced in factories that also manufacture wheat products, they can be contaminated with wheat gluten. Rarely, the intestinal injury will continue despite a strictly gluten-free diet. People with this condition, known as refractory celiac disease, have severely damaged intestines that cannot heal. Because their intestines are not absorbing enough nutrients, they may need to receive nutrients directly into their bloodstream through a vein, or intravenously. Researchers are evaluating drug treatments for refractory celiac disease. The Gluten-free Diet A gluten-free diet means not eating foods that contain wheat, rye, and barley. The foods and products made from these grains should also be avoided. In other words, a person with celiac disease should not eat most grain, pasta, cereal, and many processed foods. Despite these restrictions, people with celiac disease can eat a wellbalanced diet with a variety of foods. They can use potato, rice, soy, amaranth, quinoa, buckwheat, or bean flour instead of wheat flour. They can buy gluten-free bread, pasta, and other products from stores that carry organic foods, or order products from special food companies. Gluten-free products are increasingly available from mainstream stores. Plain meat, fish, rice, fruits, and vegetables do not contain gluten, so people with celiac disease can freely eat these foods. In the past, people with celiac disease were advised not to eat oats. New evidence suggests that most people can safely eat small amounts of oats, as long as the oats are not contaminated with wheat gluten during processing. People with celiac disease should work closely with their health care team when deciding whether to include oats in their diet. Examples of other foods that are safe to eat and those that are not are provided in the table. The gluten-free diet requires a completely new approach to eating. Newly diagnosed people and their families may find support groups helpful as they learn to adjust to a new way of life. People with celiac disease must be cautious about what they buy for lunch at school or work, what they purchase at the grocery store, what they eat at restaurants or parties, and what they grab for a snack. Eating out can be a challenge. When in doubt about a menu item, a person with celiac disease should ask the waiter or chef about ingredients and preparation or if a gluten-free menu is available. Gluten is also used in some medications. People with celiac disease should ask a pharmacist if prescribed medications contain wheat. Because gluten is sometimes used as an additive in unexpected productssuch as

lipstick and play doughreading product labels is important. If the ingredients are not listed on the label, the manufacturer should provide a list upon request. With practice, screening for gluten becomes second nature. New Food Labeling The Food Allergen Labeling and Consumer Protection Act (FALCPA), which took effect on January 1, 2006, requires food labels to clearly identify wheat and other common food allergens in the list of ingredients. FALCPA also requires the U.S. Food and Drug Administration to develop and finalize rules for the use of the term gluten free on product labels. [Top]

The Gluten-free Diet: Some Examples

In 2006, the American Dietetic Association updated its recommendations for a gluten-free diet. The following chart is based on the 2006 recommendations. This list is not complete, so people with celiac disease should discuss gluten-free food choices with a dietitian or physician who specializes in celiac disease. People with celiac disease should always read food ingredient lists carefully to make sure the food does not contain gluten. Allowed Foods amaranth legumes arrowroot millet buckwheat nuts cassava potatoes corn quinoa flax rice Indian rice grass sago Job's tears Foods To Avoid wheat including einkorn, emmer, spelt, kamut wheat starch, wheat bran, wheat germ, cracked wheat, hydrolyzed wheat protein Other Wheat Products bromated flour graham flour durum flour phosphated flour enriched flour plain flour farina Processed Foods that May Contain Wheat, Barl bouillon cubes French fries brown rice syrup gravy candy imitation fish chips/potato chips matzo

cold cuts, hot dogs, salami, sausage communion wafers

*

rice mixes sauces

Most of these foods can be found gluten-free. When in doubt, check with the food manufacturer. Source: Thompson T. Celiac Disease Nutrition Guide, 2nd ed. Chicago: American Dietetic Association; 2006. American Dietetic Association. Adapted with permission. For a complete copy of the Celiac Disease Nutrition Guide, please visit www.eatright.org . [Top]

Points to Remember
People with celiac disease cannot tolerate gluten, a protein in wheat, rye, and barley. Untreated celiac disease damages the small intestine and interferes with nutrient absorption. Without treatment, people with celiac disease can develop complications such as osteoporosis, anemia, and cancer. A person with celiac disease may or may not have symptoms. Diagnosis involves blood tests and, in most cases, a biopsy of the small intestine. Since celiac disease is hereditary, family members of a person with celiac disease may wish to be tested. Celiac disease is treated by eliminating all gluten from the diet. The gluten-free diet is a lifetime requirement. A dietitian can teach a person with celiac disease about food selection, label reading, and other strategies to help manage the disease. [Top]

Hope through Research

The National Institute of Diabetes and Digestive and Kidney Diseases conducts and supports research on celiac disease. Researchers are studying new options for diagnosing celiac disease, including capsule endoscopy. In this technique, patients swallow a capsule containing a tiny video camera that records images of the small intestine. Several drug treatments for celiac disease are under evaluation. Researchers are also studying a combination of enzymesproteins that aid chemical reactions in the bodythat detoxify gluten before it enters the small intestine. Scientists are also developing educational materials for standardized medical training to raise awareness among health care providers. The hope is that increased understanding and awareness will lead to earlier diagnosis and treatment of celiac disease. Participants in clinical trials can play a more active role in their own health care, gain access to new research treatments before they are widely

available, and help others by contributing to medical research. For information about current studies, visit www.ClinicalTrials.gov. NIH Publication No. 084269 September 2008 [Top] Page last updated January 27, 2012 Ciaran Kelly, M.D.,

Celiac disease facts

17. Celiac disease is a chronic digestive disorder in which damage to the lining of the small intestine leads to the malabsorption of minerals and nutrients. The destruction of the inner lining of the small intestine in celiac disease is caused by an immunological (allergic) reaction to gluten. Gluten is a family of proteins present in wheat, barley, rye, and sometimes oats. Individuals with celiac disease may develop diarrhea, steatorrhea, weight loss, flatulence, iron deficiency anemia, abnormal bleeding, or weakened bones. However, many adults with celiac disease may have either no symptoms or only vague abdominal discomfort such as bloating, abdominal distension, and excess gas. Children with celiac disease may have stunted growth, and if untreated, childhood celiac disease can result in short stature as an adult. Small intestinal biopsy is considered the most accurate test for celiac disease. Blood tests can be performed to diagnose celiac disease; these include endomysial antibodies, anti-tissue transglutaminase antibodies, and anti-gliadin antibodies. There is no cure for celiac disease. The treatment of celiac disease is a gluten free diet.

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In most individuals, a gluten free diet will result in improvement in symptoms within weeks. Many individuals report symptom improvement within 48 hours. In children with celiac disease, successful treatment with a gluten free diet can lead to the resumption in growth (with rapid catch up in height). Failure to respond to a gluten free diet can be due to several reasons; the most common reason is failure to adhere to a strict gluten free diet. Refractory celiac disease is a rare condition in which the symptoms of celiac disease (and the loss of villi) do not improve despite many months of a strict gluten free diet. It may progress to cancer. The treatment of refractory celiac disease is first to make sure that all gluten is eliminated from the diet. If there still is no improvement, corticosteroids such as prednisone, and immunosuppressive agents (medications that suppress a person's immune system) such as azathioprine and cyclosporine may be used. Adults with celiac disease have a several-fold higher than normal risk of developing lymphomas (cancers of the lymph glands) in the small intestine and elsewhere. They also have a high risk of small intestinal and, to a lesser degree, of esophageal carcinomas (cancers of the inner lining of the intestine and esophagus).

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The prognosis of individuals with celiac disease who develop lymphoma, collagenous celiac disease, or jejunal ulcers is poor.

What is celiac disease?

Celiac disease is a disease of the small intestine. The small intestine is a 22 foot long tube that begins at the stomach and ends at the large intestine (colon). The first 10 inches (25cm) of the small intestine (the part that is attached to the stomach) is called the duodenum, the middle part is called the jejunum, and the last part

(the part that is attached to the colon) is called the ileum. Food empties from the stomach into the small intestine where it is digested and absorbed into the body. While food is being digested and absorbed, it is transported by the small intestine to the colon. What enters the colon is primarily undigested food. In celiac disease, there is an immunological (allergic) reaction within the inner lining of the small intestine to proteins (gluten) that are present in wheat, rye, barley and, to a lesser extent, in oats. The immunological reaction causes inflammation that destroys the lining of the small intestine. This reduces the absorption of the dietary nutrients and can lead to symptoms and signs of nutritional, vitamin, and mineral deficiencies. The other terms used forceliac disease include sprue, nontropical sprue, gluten enteropathy, and adult celiac disease. (Tropical sprue is another disease of the small intestine that occurs in tropical climates. Although tropical sprue may cause symptoms that are similar to celiac disease, the two diseases are not related.) Celiac disease is common in European countries, particularly in Ireland, Italy, Sweden, and Austria. In Northern Ireland, for example, one in every 300 people has celiac disease. In Finland, the prevalence may be as high as one in every 100 persons. Celiac disease also occurs in North America where the prevalence has been estimated to be one in every 3000 people. Unfortunately, most population studies underestimate the prevalence of celiac disease because many individuals who develop celiac disease have few or no symptoms until later in life. Moreover, a study suggests that the prevalence of celiac disease in the United States is similar to that in Europe.

What causes celiac disease?

The destruction of the inner lining of the small intestine in celiac disease is caused by an immunological (allergic) reaction to gluten in the diet that inflames and destroys the inner lining of the small intestine. There is evidence that this reaction is partially genetic and partially inherited. Thus, approximately 10% of the first-degree relatives (parents, siblings or children) of individuals with celiac disease also will have celiac disease. In addition, in approximately

30% of fraternal twins and 70% of identical twins, both twins will have celiac disease. Finally, certain genes have been found to be more common in individuals with celiac disease than in those without celiac disease. Gluten is a family of proteins present in wheat. Some of the proteins that make up gluten (the ones that are dissolved by alcohol) are called gliadin. It is the gliadin in gluten that causes the immunological reaction in celiac disease. The mechanism whereby gliadin becomes toxic (damaging) is not clear; however, much scientific study is being done, and we are beginning to understand the mechanism. Proteins, including gliadin, are long chains of amino acids--up to several hundred--attached to each other. Normally during digestion, the digestive enzymes within the small intestine break-up proteins into single amino acids and smaller chains of amino acids. This is necessary because the intestine can only absorb single amino acids or, at most, chains of 3-4 amino acids. Single amino acids and chains of several amino acids do not cause problems for the intestine. It appears, however, that gliadin is not completely broken-up by intestinal enzymes. Several longer chains of amino acids remain intact. Somehow these larger chains enter the cells lining the intestine, perhaps because the cells are abnormally permeable (leaky) to longer chains of amino acids. Some of these longer chains are toxic (damaging) to the intestinal cells. One of the longer chains attaches to an enzyme (tissue transglutaminase) inside the cells. In individuals with celiac disease, the complex of the longer chain of amino acids and tissue transglutaminase sets off an immune reaction that attacks the complex and at the same time damages the intestinal cells. Barley and rye contain gliadin-like proteins and can cause celiac disease in genetically-predisposed individuals. Oats also contain gliadin-like proteins, but unlike barley and rye, the gliadin-like proteins in oats cause only a mild inflammation and that too in only a few individuals who are predisposed to develop celiac disease. Rice and corn do not cause celiac disease because they do not contain gliadinlike proteins.

What does celiac disease do to the small intestine? The small intestine has an inner lining of cells that form finger-like projections called villi. The villi are important because they increase the urface area available for the absorption of nutrients from the intestinal lumen into the blood stream. In celiac disease, the inflammation destroys the villi, causing the inner lining of the small intestine to become flattened. This loss of villi reduces the number of cells and the surface area available for absorption of nutrients. The impaired absorption of nutrients is referred to as malabsorption. The malabsorption of nutrients leads to nutrient deficiencies, referred to as malnutrition. The length (amount) of the small intestine affected by the loss of villi varies from patient to patient, and the length that is involved determines the severity of signs and symptoms. Thus, individuals whose entire small intestine is affected by the loss of villi have more severe signs and symptoms of malabsorption than individuals who have only a part of the small intestine affected. When only a part of the small intestine is affected, usually the upper small intestine (the duodenum and jejunum) is affected more than the lower small intestine (the ileum).

What are the signs and symptoms of celiac disease?

The signs and symptoms of celiac disease vary depending on the degree of malabsorption, and ranges from no symptoms, few or mild signs and symptoms, to severe signs and symptoms. There are two categories of signs and symptoms: 1) signs and symptoms due to malabsorption, and 2) signs and symptoms due to malnutrition including vitamin and mineral deficiencies. 1. Signs and symptoms of malabsorption The three major categories of dietary nutrients are carbohydrates, proteins, and fat. Absorption of all of these nutrients can be reduced

in celiac disease; however, fat is the most commonly and severely affected nutrient. Most of the gastrointestinal symptoms and signs of celiac disease are due to the inadequate absorption of fat (fat malabsorption). Gastrointestinal symptoms of fat malabsorption include diarrhea, malodorous flatulence (foul smelling gas), abdominal bloating, and increased amounts of fat in the stool (steatorrhea). The unabsorbed fat is broken down by intestinal bacteria into fatty acids, and these fatty acids promote secretion of water into the intestine, resulting in diarrhea. Fatty stools typically are large in volume, malodorous (foul smelling), greasy, light tan or light grey in color, and tend to float in the toilet bowl. Oil droplets (undigested fat) also may be seen floating on top of the water. Loss of intestinal villi also causes malabsorption of carbohydrates, particularly the sugar lactose. Lactose is the primary sugar in milk. Lactose is made up of two smaller sugars, glucose and galactose. In order for lactose to be absorbed from the intestine and into the body, it must first be split into glucose and galactose. The glucose and galactose can then be absorbed by the cells lining the small intestine. The enzyme that splits lactose into glucose and galactose is called lactase, and it is located on the surface of the small intestinal villi. In celiac disease the intestinal villi along with the lactase enzymes on their surface are destroyed, leading to the malabsorption of lactose. The signs and symptoms of malabsorption of lactose are particularly prominent in individuals with celiac disease who have an underlying lactose intolerance, a genetically determined reduction in the activity of lactase. The symptoms of lactose malabsorption (diarrhea, excessive flatulence [passing gas], abdominal pain and abdominal bloating or distension) occur because unabsorbed lactose passes through the small intestine and into the colon. In the colon, the normal colony of bacteria contain lactase and are able to split the lactose, and utilize the resulting glucose and galactose for their own purposes. Unfortunately, when they split the lactose into glucose and galactose, the bacteria also release gas (hydrogen and /or methane). A proportion of the gas is expelled and is responsible for the increased flatus (passing gas) that may occur in celiac disease. Increased gas mixed in the stool is responsible for the stools to float in the toilet bowl.

Not all of the lactose that reaches the colon is split and used by the colonic bacteria. The unsplit lactose that reaches the colon causes water to be drawn into the colon (by osmosis). This promotes diarrhea. 2. Signs and symptoms of malnutrition and vitamin or mineral deficiencies Symptoms of malnutrition and vitamin or mineral deficiencies include: weight loss, fluid retention, anemia, osteoporosis, bruising easily, peripheral neuropathy (nerve damage), infertility, and muscle weakness. 31. Weight loss and fluid retention: Weight loss is the direct result of inadequate absorption of carbohydrates, proteins and fat. However, weight loss may not always occur because individuals with celiac disease often have an enormous appetite that compensates for the reduced absorption of nutrients. Moreover, weight loss can be masked by fluid retention. Fluid retention occurs in advanced malnutrition because the reduced absorption of proteins results in low protein levels in the blood. Normal protein levels in the blood are necessary to keep fluid from leaking out of blood vessels and into the body's tissues. When blood protein levels fall as in celiac disease, fluid leaks into many tissues (edema) but particularly the ankles and feet, which swell due to the edema. Anemia: Lack of absorption of vitamin B12 and iron can lead to anemia. Osteoporosis: Lack of absorption of vitamin D and calcium can lead to osteoporosis and bone fractures. Easy bruising: Lack of absorption of vitamin K can lead to diminished ability of blood to clot and hence to easy bruising or excessive bleeding. Peripheral neuropathy (nerve damage): Deficiencies of

32. 33. 34.

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vitamins B12 and thiamine may contribute to nerve damage with symptoms of poor balance, muscle weakness, and numbness and tingling in the arms and legs. 36. Infertility: Untreated celiac disease can lead to infertility in women, lack of menses (menstruation), spontaneous abortions and low birth weight infants. Muscle weakness: Lack of absorption and low levels of potassium and magnesium can lead to severe muscle weakness, muscle cramps, and numbness or tingling sensations in the arms and legs.

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Abnormal liver tests: For unclear reasons, patients with celiac disease may have abnormal blood tests that suggest liver injury, specifically, elevated levels of aspartate amino transferase (AST) and/or leucine amino transferase (ALT). Occasionally, abnormalities of these tests may lead to a suspicion and subsequently a diagnosis of celiac disease.

How do symptoms of celiac disease differ with age of onset?

In the past, celiac disease was considered to be a disease primarily of infants and children. It is now clear that the initial signs and symptoms of celiac disease can occur in adults and even in the elderly. Symptoms in infants Infants with celiac disease typically have diarrhea, steatorrhea, abdominal cramps, abdominal distension, irritability, muscle wasting, and failure to thrive and grow. These symptoms typically occur after the introduction of gluten-containing cereals into their diets. Symptoms in children Children with celiac disease typically have diarrhea, increased

amounts of fat in the stool (steatorrhea), flatulence (passing gas), short stature and weight loss. Proper treatment with a gluten-free diet can lead to accelerated (catch-up) growth in height; however, if untreated, childhood celiac disease can result in short stature as an adult. As children with celiac disease enter adolescence, many will experience spontaneous remissions (reduced symptoms) and remain free of the signs and symptoms of celiac disease until later in adulthood. This later reactivation may be precipitated by stress such as pregnancy or surgery. Symptoms in adults Adults with celiac disease may have symptoms of diarrhea, steatorrhea, weight loss and flatulence; however, many adults do not have diarrhea or steatorrhea. They have either no symptoms or only vague abdominal discomfort such as bloating, abdominal distension and excess gas. They also may have one, or only a few signs of malnutrition such as iron deficiency anemia, abnormal bleeding, or bone fractures. Some individuals with celiac disease and gastrointestinal symptoms are mistakenly diagnosed to have irritable bowel syndrome (IBS). There have been changes during the past 20 years in the way in which celiac disease is diagnosed. The average age at which celiac disease is diagnosed has increased, probably because of the increased awareness that the disease can first cause symptoms or signs in adults. Whereas in the past, diarrhea was the initial symptom in 80% of patients, it now is the initial symptom in only 40%. A small proportion of patients - about 15% - are now diagnosed with blood antibody tests because they have a close relative with celiac disease and they are being screened to see if they also have the disease.

What is latent and silent celiac disease?

The terms latent and silent celiac disease are used to refer to individuals who have inherited the genes that predispose them to celiac disease but have not developed the symptoms or signs of

celiac disease. Latent celiac disease refers specifically to individuals who have abnormal antibody blood tests for celiac disease (see discussion of specific tests for celiac disease) but who have normal small intestine and no signs or symptoms of celiac disease. For example: 38. Some individuals may have had a childhood onset of celiac disease and the disease may have been successfully treated with a gluten-free diet. The individuals' intestines may have resumed a normal appearance and function, and they may have no signs or symptoms of celiac disease. Some individuals with celiac disease in childhood abandon the gluten free diet as adults, yet they remain free of the signs or symptoms of celiac disease.

39.

In both of the above instances, the celiac disease is latent, and the individuals can develop signs and symptoms of celiac disease later in life. Silent celiac disease refers to individuals who have abnormal antibody blood tests for celiac disease as well as loss of villi in the small intestine but have no symptoms or signs of celiac disease, even on a diet that contains gluten. Like individuals with latent celiac disease, these people can develop signs or symptoms of celiac disease later in life.

What diseases are associated with celiac disease?

The following diseases are associated with celiac disease: An estimated 10% of individuals with celiac disease also have dermatitis herpetiformis. Dermatitis herpetiformis is a disease of the skin that is characterized by an itchy rash on the

extremities, buttocks, neck, trunk, and scalp. Recurrent painful mouth ulcers (aphthous stomatitis)

How is celiac disease diagnosed?

Celiac disease is suspected when individuals have signs or symptoms of malabsorption or malnutrition. Other diseases, however, can produce malabsorption and malnutrition, for example, pancreatic insufficiency (when the pancreas is not able to produce digestive enzymes), Crohn's disease of the small intestine, and small intestinal overgrowth of bacteria. It is important, therefore, to confirm suspected celiac disease with appropriate testing. Small intestinal biopsy Small intestinal biopsy is considered the most accurate test for celiac disease. Small intestinal biopsies can be obtained by performing an esophagogastroduodenoscopy (EGD). During an EGD, the doctor inserts a long, flexible viewing endoscope through the mouth and into the duodenum. A long, flexible biopsy instrument is then passed through a small channel in the endoscope to obtain samples of the intestinal lining of the duodenum. Multiple samples usually are obtained to increase the accuracy of the diagnosis. A pathologist then can examine the biopsies (under a microscope) for the loss of villi and other characteristics of celiac disease such as increased numbers of lymphocytes. Small intestinal biopsy does however, have some limitations. For example, acute viral gastroenteritis and allergy to cow's milk or soy protein can cause abnormal small intestinal biopsies that are indistinguishable from celiac disease. However, acute viral gastroenteritis is not easily confused with celiac disease because of the difference in the acuteness of symptoms. (Acute viral

gastroenteritis has a sudden onset of symptoms and last only a few days.) It is however, easier to confuse cow's milk and soy protein allergies with celiac disease, but these allergic conditions are rare and primarily occur in young children. Despite these limitations, small intestinal biopsies are recommended even in individuals who have abnormal antibody tests for celiac disease. (See discussion that follows.) Specific antibody tests for celiac disease Antibodies are proteins that are produced by the immune system to fight viruses, bacteria, and other organisms that infect the body. Sometimes, however, the body produces antibodies against noninfectious substances in the environment (for example, hay fever) and even against its own tissues (autoimmunity). Blood tests that are specific for celiac disease include antigliadin antibodies, endomysial antibodies, and anti-tissue transglutaminase antibodies. In patients with celiac disease, anti-gliadin antibody is produced against gliadin in the diet, and anti-tissue transglutaminase antibodies are antibodies produced against the body's own tissues. Endomysial antibodies and anti-tissue transglutaminase antibodies are highly reliable in diagnosing celiac disease. An individual with an abnormal elevation of these antibodies has a greater than 95% chance of having celiac disease. Anti-gliadin antibodies are less reliable and have a high false positive rate. Thus a person with an abnormally elevated anti-gliadin antibody level does not necessarily have celiac disease. Nevertheless, anti-gliadin antibody levels are useful in monitoring the response to treatment because anti-gliadin antibody levels usually begin to fall within several months of successful treatment of celiac disease with a gluten free diet. The newest test for celiac disease is a test for antibodies to parts of the gliadin molecule called deamidated gliadin peptides. This test appears to be as good for diagnosing celiac disease as antibodies to tissue transglutaminase. In fact, it has been speculated that if blood

tests for antibodies to tissue transglutaminase and deamidated gliadin peptides are negative (that is, no antibodies are present) then celiac disease is virtually excluded, and perhaps there is no need for biopsies of the small intestine. Further studies will be needed, however, to prove this. Who should undergo antibody blood tests for celiac disease? Some experts recommend that antibody blood tests should be used to screen healthy persons with no signs or symptoms for celiac disease. In Italy, where celiac disease is common, all children are screened for celiac disease. Experts in the United States do not recommend screening healthy persons for celiac disease. Antibody blood tests are only recommended for individuals with a higher likelihood than normal of having celiac disease. These individuals are: 40. Individuals with chronic diarrhea (diarrhea that does not resolve in three weeks), increased amount of fat in the stool (steatorrhea), and weight loss Individuals with excess gas, bloating, and abdominal distension First and second degree relatives of individuals who have celiac disease Children with growth retardation Individuals with unexplained iron deficiency anemia Individuals with skin rashes suggestive of dermatitis herpetiformis Individuals with recurrent painful mouth sores (aphthous stomatitis) Individuals with diseases known to be associated with celiac disease. Examples of these diseases include insulin-dependent diabetes mellitus, autoimmune thyroid disease, rheumatoid

41. 42. 43. 44. 45. 46. 47.

arthritis, systemic lupus, ulcerative colitis, etc. 48. Individuals with unexplained elevations of liver enzymes (AST or ALT) in the blood.

Why is it important to accurately diagnose celiac disease? Diagnosis of celiac disease should be firmly established before commencing treatment with a gluten free diet for several reasons. The gluten free diet is a life-long and tedious commitment that should not be taken lightly. It is more costly than a normal diet and has significant social implications, especially when dining out. Individuals with irritable bowel syndrome (IBS) may experience improvement in bloating, abdominal pain, and diarrhea with a gluten free diet. These individuals may be misdiagnosed as having celiac disease. Without confirmation of celiac disease by small intestinal biopsy, they may be unnecessarily committed to life-long gluten restriction. A gluten free diet can lower blood antibody levels and allows the microscopic appearance of the small intestine to lose the typical appearance of celiac disease, complicating subsequent efforts at making a firm diagnosis of celiac disease. How are malabsorption and malnutrition evaluated in celiac disease? Celiac disease causes malabsorption of nutrients and leads to malnutrition. Tests are available that help in the evaluation of malabsorption and malnutrition; however, because other diseases can cause both malabsorption and malnutrition, these tests cannot be used to diagnose celiac disease. Stool examination for malabsorption

Fat in a sample of stool placed on a glass slide can be stained with a dye (Sudan stain) to make the fat visible under the microscope as globules. Stool from patients with celiac disease often contains many stained globules of fat, and Sudan staining is a quick and easy screening test for increased amounts of fat in the stool (steatorrhea). To conclusively diagnose steatorrhea, however, stool is collected over a 72-hour period, and the fat in the stool is chemically measured and quantified. Steatorrheic stools have abnormally high quantities of fat. Since malabsorption and steatorrhea can occur with other intestinal diseases (such as small intestinal bacteria overgrowth, small intestinal resection, extensive Crohn's disease of the small intestine, and chronic pancreatitis), stools with large amounts of fat only raises the suspicion of celiac disease but cannot be used to diagnose celiac disease. Blood tests for malnutrition and vitamin deficiencies Malabsorption reduces the absorption of protein and causes a reduction in blood protein levels. This can be seen commonly as a reduced blood level of albumin, the most concentrated protein in blood. Other proteins in blood, for example, transferrin also may be reduced. Intestinal malabsorption can lead to deficiencies and low blood levels of iron, calcium, vitamin B12, folate, Vitamin D and vitamin K. These deficiencies, in turn, can lead to other blood test abnormalities such as: Iron deficiency anemia: Iron is an important component of hemoglobin in red blood cells. When iron is deficient, the production of red blood cells is impaired, and anemia develops. Iron deficiency anemia can occur either through loss of blood (with its iron-containing red blood cells) or lack of intestinal iron absorption. Heavy menstrual bleeding and cancer of the colon that bleeds into the intestine are two common causes of iron deficiency anemia due to blood loss. Celiac disease causes iron deficiency anemia by reducing intestinal iron absorption. In fact, iron deficiency anemia can be an important clue to the

presence of celiac disease. Abnormally prolonged prothrombin time (ProTime): ProTime is a blood test that measures how quickly blood clots. Clotting of blood requires special proteins or clotting factors, many of which are made by the liver. Formation of clotting factors by the liver requires vitamin K. When vitamin K absorption from the intestine is reduced, as in celiac disease, the production of clotting factors by the liver is inadequate, and blood clotting is delayed. Delayed clotting is reflected in an abnormal ProTime, and individuals with an abnormal ProTime have a higher risk of abnormal or excessive bleeding. Iron deficiency anemia, abnormal ProTime, steatorrhea, and low iron and vitamin levels can occur in diseases other than celiac disease. Therefore, the presence of these abnormalities only raises the suspicion of celiac disease but does not specifically diagnose celiac disease.

What is the treatment of celiac disease?

There is no cure for celiac disease. The treatment of celiac disease is a gluten free diet. Patients with celiac disease vary in their tolerance to gluten; some patients can ingest small amounts of gluten without developing symptoms while others experience massive diarrhea with only minute amounts of gluten. The standard treatment calls for complete avoidance of gluten for life. The principles of a gluten free diet include: 49. Avoid all foods made from wheat, rye, and barley. Examples are breads, cereals, pasta, crackers, cakes, pies, cookies, and gravies. Avoid oats. Some individuals with celiac disease can tolerate oats in the diet. But long-term safety of oats in individuals with celiac disease is unknown. Also some oat preparations can be contaminated with wheat. Thus, it is probably best to avoid oats at least during the initial treatment with a gluten free diet. Once disease remission is achieved with a strict gluten free diet, small quantities of oats may be reintroduced into the diet under

50.

medical supervision. 51. Pay attention to processed foods that may contain gluten. Wheat flour is a common ingredient in many processed foods. Examples of foods that may contain gluten, to name only a few, include: canned soups, salad dressings, ice cream, candy bars, instant coffee, luncheon meats, ketchup, mustard, processed and canned meats, yogurt, sausages and, pasta. 52. 53. Beware of tablets, capsules, and vitamin preparations that contain gluten. Wheat starch is commonly employed as a binding agent in tablets and capsules. Gluten also can be found in many vitamin products, and cosmetic products such as lipstick. Avoid beer

54.

55. 56.

It is all right to drink wine, brandy, whiskey and other non-wheat or barley alcohol (in moderation!) Avoid milk and other dairy products that contain lactose. Untreated individuals with celiac disease often are lactose intolerant. With successful treatment, dairy products can be reintroduced slowly into the diet. It is alright to consume fish, fresh meats, rice, corn, soybean, potato, poultry, fruits, vegetables, and dairy products (for individuals who are not lactose intolerant) Consult dietitians and national celiac disease societies for lists of gluten free foods. Read the food and product labels before buying or consuming any product. This is necessary because a manufacturer may change a product's ingredients at any time. A product that was gluten-free in the past may now contain gluten. Even branded products may be gluten free in one country but contain gluten in another country. If one is not certain after reading the labels, call the manufacturer. Because individuals with severe malabsorption can develop vitamin and mineral deficiencies, vitamin and mineral supplements are important. All individuals should take a multivitamin daily. Individuals with iron deficiency anemia should be treated with iron. Individuals with anemia due to folate or B12 deficiency should be treated with folic acid and B12. Individuals with an abnormal ProTime should be treated with vitamin K. Individuals with low blood calcium levels or with osteoporosis should be treated with calcium and vitamin D supplements.

57.

58.

59.

In most individuals, a gluten free diet will result in improvements in symptoms within weeks. Many individuals report symptom improvements within 48 hours. In children with celiac disease, the response to a gluten free diet can be dramatic. Not only will diarrhea and abdominal discomfort subside, but the child's behavior also improves, and growth resumes (with rapid catch up in height). These improvements in symptoms are followed by reappearance of intestinal villi. Complete normalization of the intestinal villi may take

months. In many adult individuals, the improvement in symptoms is followed by only partial regeneration of intestinal villi. In individuals with dermatitis herpetiformis, the skin lesions also improve with a gluten free diet. Many individuals with celiac disease may not understand the importance of life-long adherence to a gluten free diet. A study found that in patients diagnosed at least 20 years earlier with celiac disease, only half of the patients were following a strict gluten-free diet. The primary reason that patients followed the diet was to prevent symptoms-not to prevent complications. There was evidence of mild iron deficiency and abnormal bone density in one-third of the patients, suggesting that the lack of adherence to the diet was having health consequences.

What if individuals don't respond to gluten free diet?

Failure to respond to a gluten free diet can be due to several reasons: 60. 61. The person is not following a strict gluten free diet and is still eating small amounts of gluten. The person is unknowingly ingesting unsuspected sources of gluten such as starch, binders and fillers in medications or vitamins. The person may have another co-existing condition such as irritable bowel syndrome, bacterial overgrowth of the small bowel, microscopic colitis, or pancreatic insufficiency that is causing the symptoms. The person may have refractory disease, or complications of celiac disease.

62.

63.

What is refractory celiac disease?

Refractory celiac disease is a rare condition in which the symptoms of

celiac disease (and the loss of villi) do not improve despite many months of a strict gluten free diet. Before making a diagnosis of refractory celiac disease it is important to exclude complications of celiac disease and other co-existing conditions that can produce similar symptoms and biopsy findings. Refractory celiac disease is believed to consist of two different entities, one which is relatively benign and one which becomes malignant or cancerous. Special examination of intestinal tissue from patients with refractory celiac disease can differentiate between the two entities.

What is the treatment for refractory celiac disease?

The treatment of refractory celiac disease is first to make sure that all gluten is eliminated from the diet. If there still is no improvement, medications are used. Corticosteroids such as prednisone have been used successfully in treating some patients with refractory celiac disease. Immuno-suppressive drugs (medications that suppress a person's immune system) such as azathioprine (Imuran, Azasan) and cyclosporine also have been used. Corticosteroids and immunosuppressive drugs are potent medications with potentially serious side effects. Many patients with refractory celiac disease are malnourished and have weakened immune systems, and corticosteroids and immunosuppressive agents can further increase their risk of serious infections. Thus doctors experienced with treating celiac disease should monitor treatment of refractory celiac disease. Unfortunately in some patients with refractory celiac disease, malabsorption and malnutrition progress despite drugs. In these

patients the intravenous route is the only way to deliver nutrition. Total parenteral nutrition (TPN) is a way of delivering calories, carbohydrates, amino acids, and fat in liquid solutions via a catheter that has been inserted and secured into a vein.

What are the complications of celiac disease?

The complications of celiac disease include cancers, small bowel ulcers (ulcerative jejunoileitis), and collagenous celiac disease. Cancer Adults with celiac disease have a several-fold higher than normal risk of developing lymphomas (cancers of the lymph glands) in the small intestine and elsewhere. They also have a high risk of small intestinal and, to a lesser degree, esophageal carcinomas (cancers of the inner lining of the intestine and esophagus). Lymphoma tends to develop in adults who have had celiac disease for longer than 20-30 years and in those with refractory celiac disease. Symptoms of small intestinal lymphoma or carcinoma include anemia, bleeding into the intestine, abdominal pain, weight loss, fever, and small intestinal obstruction (with symptoms of abdominal distension, vomiting and crampy abdominal pain). Small intestinal lymphoma and carcinoma are difficult to diagnose. Sometimes in individuals with celiac disease, where the disease has been controlled with a gluten free diet, recurrence of weight loss, anemia, abdominal pain, and symptoms of intestinal obstruction will lead doctors to search for intestinal lymphoma and carcinoma. Computerized tomography (CT) scans of the abdomen, enteroclysis (one type of barium X-ray of the small intestine), and enteroscopy (inspection of the small intestine using a long, flexible endoscope) are procedures doctors use to diagnose small intestinal lymphoma and carcinoma. Sometimes the diagnosis of intestinal lymphoma or carcinoma can only be made with surgery (open laparotomy) or by laparoscopy (examination of the abdominal cavity with flexible endoscopes). The prognosis for individuals who develop intestinal lymphoma usually is poor. Long-term survival (survival beyond 5

years) of patients with small intestinal lymphoma is estimated to be only 10%. Other cancers that may be increased in individuals with celiac disease include cancers of the liver, oral cavity, and large intestine. Ulcerative jejunoileitis Ulcerative jejunoileitis is a rare complication of celiac disease. In ulcerative jejunoileitis there are recurrent episodes of small intestinal ulcerations and formation of strictures (narrowing of the intestinal lumen). Small intestinal ulcerations and stricture formation can lead to intestinal bleeding, weight loss, abdominal pain, and intestinal obstruction. Individuals with ulcerative jejunoileitis are at a high risk of developing intestinal lymphomas. The diagnosis of ulcerative jejunoileitis is made by enteroclysis of the small intestine, enteroscopy, or CT scan of the abdomen. Treatment involves a gluten free diet and surgical resection of the most diseased portions of the small intestine. The prognosis is poor; long-term survival for individuals with ulcerative jejunoileitis beyond 5 years is less than 50%. Collagenous celiac disease Collagenous celiac disease is a rare, but serious complication of celiac disease in which a patient may have the symptoms of celiac disease initially, but they fail to improve on a gluten free diet, and after several years a large amount of scar tissue (collagen) forms just under the intestinal lining. There is no treatment for collagenous celiac disease, and the prognosis is poor.

Can cancer risk be reduced in celiac disease?

Some doctors believe that strict adherence to a gluten free diet can reduce the risk of cancer in individuals with celiac disease, but further studies are needed to prove this. Until more is known in this area, persons with celiac disease should adhere strictly to a gluten free diet.

What's new in celiac disease?

The way in which gluten and gliadin cause disease appears to be complex. It does not appear to be simply a matter of an immune response to gliadin. Current information suggests that partially digested gliadin from the intestine is altered by tissue transglutaminase in the small intestine. These altered products of gliadin digestion are what provoke the immunologic response that leads to the production of antibodies to tissue transglutaminase and the inflammation that destroys the villi. The symptoms of celiac disease can be similar to those of irritable bowel syndrome (IBS), and the issue often arises if patients with IBS need to be screened for celiac disease. If they are screened, should they be screened with blood antibody tests, small intestinal biopsies, or both? One study in particular has addressed this issue. Approximately 100 patients thought to have diarrhea from IBS were studied. Among the IBS patients, none had celiac disease-associated antibodies in their blood, but 30% had the antibodies in the juice obtained from within the duodenum. Twenty-three percent of the patients with IBS had lymphocytes in the lining of the small intestine just like patients with celiac disease. Finally, 35% of the IBS patients had the genes that are commonly found in celiac disease. These interesting findings need to be confirmed by additional studies. If confirmed, they would suggest that a proportion of patients with IBS may actually have celiac disease, and that the diagnosis might require small intestinal biopsy and antibody studies of the duodenal juice. Another confusing issue is the fact that many people state that their gastrointestinal symptoms have improved by eliminating gluten from their diet despite the fact that all of the blood tests for celiac disease are negative and, in some cases, even the biopsies of the small intestine are normal. There are two possible explanations for this. The first is a placebo effect, that is, people think they feel better but they probably are not better. (It is sobering to know that this placebo

response may occur in as many as 20%-40% of people.) The other explanation is that gliadin-containing grains also contain fructans, complex carbohydrates that are not digested in the human small intestine. These fructans enter the colon where colonic bacteria can ferment them. The products of fermentation can give rise to gastrointestinal symptoms, particularly bloating, gas and diarrhea. It is not clear how many people who feel better by eliminating gluten from their diet have intolerance to fructans rather than celiac disease.
REFERENCE: eMedicine.com. Celiac Disease. <http://emedicine.medscape.com/article/932104-overview> Original author and editor Dennis Lee, M.D. and Jay W. Marks, M.D. (respectively).

Last Editorial Review: 6/28/2011

http://www.medicinenet.com/celiac_disease/page10.htm
Birthday cake. Pizza. Chocolate chip cookies. For people with celiac disease, a lifelong disorder of the digestive system, these foods aren't always the treats that most people think they are. Why? Because they usually contain a type of protein called gluten, which causes problems for people with celiac disease.

What Is Gluten?

Gluten is the common term for a group of proteins found in wheat, rye, barley, and grains derived from them or having different names like triticale, durum, kamut, semolina, and spelt. Grains are so common in our diet that gluten is second only to sugar as our most commonly consumed ingredient.

What Is Celiac Disease?

The digestive system is the set of organs that digest food and absorb the important nutrients the body needs to stay healthy and grow. One important part of the digestive system is the small intestine, which is lined with millions of microscopic, finger-like projections called villi (pronounced: vih-lye). Nutrients are absorbed into the body through the villi. People who have celiac (pronounced: see-lee-ak) disease have a disorder that makes their bodies react to gluten. When they eat gluten, an immune system reaction to the protein gradually damages the villi in the small intestine. When the villi are damaged, the body is unable to absorb the vitamins, minerals, and other nutrients it needs to stay healthy. People with celiac disease are therefore at risk of malnutrition and can develop anemia (a decreased number of red blood cells due to lack of iron) or osteoporosis (brittle bones from lack of calcium). The body's inability to absorb nutrients can also mean that young people with untreated celiac disease may not grow properly and may have weight loss and fatigue. In addition, people who have celiac disease may be prone to developing other diseases, such as thyroid disease, type 1 diabetes, and gastrointestinal cancer.

What Causes It?

Experts don't know exactly why people get celiac disease, which is also called gluten intolerance, celiac sprue, nontropical sprue, or glutensensitive enteropathy. The disease has some genetic background, which means that it may run in families. Just like eye or hair color, people inherit the genes that make them more likely to get celiac disease from their parents and grandparents. If an immediate family member (such as a parent or a sibling) has celiac disease, there's about a 5% to 10% chance that you could have it, too. Celiac disease affects people of all heritages and backgrounds. It is estimated that 1 in 133 people in the United States has the condition, although many don't know that they do.

Signs and Symptoms

It's important to diagnose celiac disease early before it causes damage to the intestine. But because it's easy to confuse the symptoms with other intestinal disorders, such as irritable bowel syndrome or lactose intolerance, teens with celiac disease may not know they have it. Some common symptoms of celiac disease are diarrhea, abdominal pain and bloating, and weight loss. Someone with the disease may feel tired and could be irritable or depressed. Some have skin rashes and mouth sores. Teens with undiagnosed celiac disease may go through puberty late. Someone might not show any symptoms until going through an emotionally or physically stressful event, such as going away to college, illness, or an injury or pregnancy.

How Is Celiac Disease Diagnosed?

Because the symptoms of celiac disease are similar to some other digestive conditions, only a doctor can tell for sure if a person has the disease. First the doctor will do a medical history, where he or she will ask you about any concerns and symptoms you have, your past health, your family's health, any medications you're taking, any allergies you have, and other issues. In addition to doing a medical history, your doctor will do a physical examination.

If a doctor suspects someone has celiac disease, he or she will probably order a blood test as a first step in diagnosing the disease. If the results of the blood test show a high level of antibodies to gluten and to certain other proteins in the intestinal lining a sign that the person could have celiac disease then the doctor may order a biopsybiopsy of the small intestine to confirm the diagnosis. In the case of celiac disease, doctors take a tissue sample from the small intestine by inserting a long, thin tube called an endoscope through the mouth and stomach into the small intestine. A person is fully or moderately sedated during this procedure. In many cases, a doctor may put a person to sleep with general anesthesia. The sample is sent to a laboratory for testing.

How Is It Treated?
Once celiac disease is diagnosed, a doctor will help treat it. Although there is no cure, celiac disease can be managed successfully by following a gluten-free diet. People with celiac disease need to follow this diet for life. Because gluten can be found in everything from breakfast cereals to prepared luncheon meats, they need to be very aware of what's in the foods they eat. If you've been diagnosed with celiac disease, a doctor or dietitian who specializes in celiac disease can help you develop an eating plan that works with your lifestyle. Luckily, the small intestine can heal. Although this process may take up to a year, many people start to feel better after just a few days on a gluten-free diet. But feeling better doesn't mean that people with celiac disease can resume eating foods containing gluten. Because the genes that cause the disease are present in the body and the immune system continues to react to gluten, the symptoms and problems will return if someone with celiac disease starts eating gluten again.

Eating Out
If you have celiac disease, you don't have to limit yourself to eating at home. With experience and knowledge, you'll be able to figure out which dishes at restaurants or friends' homes contain gluten. You may even have some restaurants in your town that offer gluten-free dishes on their menus. Your local support group may be able to provide a list of restaurants where the chef is familiar with the gluten-free diet. Ask at restaurants or consult your dietitian or a celiac disease support

group for this type of information. Sometimes, no matter how well prepared you are, you might not be able to find out if a particular food is gluten free. When in doubt, leave it out! Here are some tips to remember when choosing foods for celiac disease: Start with the foods you can eat. Foods and ingredients that you can eat and use in cooking include: foods made with the flours of corn, rice, buckwheat, sorghum, arrowroot, garbanzo beans (chickpeas), quinoa, tapioca, teff, and potato (provided other ingredients in your recipe do not contain gluten). You can also eat all plain meat, fish, chicken, legumes, nuts, seeds, oils, milk, cheese, eggs, fruits, and vegetables. Be on the lookout for possible cross-contamination. Even when eating or preparing foods that are gluten free, if these foods come into contact with foods that contain gluten, you run the risk of something called cross-contamination. For example, crumbs from regular wheat bread can find their way into jams, spreads, or condiments if people aren't careful to use a fresh knife or utensil each time. Keeping condiments in squeezable bottles or using separate jams and spreads is a great idea for people with celiac disease. It's also a good idea to keep a separate toaster for gluten-free bread. If someone in your family bakes with products that contain gluten, you need to thoroughly clean appliances, utensils, and work surfaces before preparing your gluten-free products. Remember to wash your hands thoroughly and often. If the food manufacturing environment is not a dedicated gluten-free environment, there is the potential for contamination. For example, gluten-free bread prepared in a bakery that also produces regular products may be contaminated. This can happen when machinery is not properly cleaned between the production of gluten-containing and gluten-free products. Some manufacturers are now producing products in gluten-free environments.

Foods and Ingredients to Avoid

A U.S. law helps make checking labels for gluten a bit easier. Since

January 2006, all food labels are required to clearly state if the food contains any of the top eight food allergens, including wheat. However, wheat free doesn't mean gluten free. Lawmakers are also working to make labels easier for people with celiac disease by requiring companies to identify other components, such as hidden ingredients and barley and rye. Still, it helps to know the foods to avoid. These include: 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. beer and other grain-based alcohol products bouillons and broths breading (such as the coating on breaded chicken cutlets, etc.) brown rice syrup (frequently made from barley) cake flour (made from wheat) caramel color (occasionally made from barley) communion wafers couscous creamed or breaded vegetables dextrin (a rare ingredient, which may be made from wheat; maltodextrin is OK for people with celiac disease) dry roasted nuts (processing agents may contain wheat flour or flavorings) fried chicken french fries (if they've been coated in flour) gravies and sauces (including some tomato and meat sauces) imitation bacon, crab, or other seafood luncheon and processed meats malt or malt flavoring (usually made from barley) marinades matzo modified food starch (most food manufacturers will now specify the source of this ingredient; e.g., modified cornstarch, which is OK, or modified wheat starch, which is not) nondairy creamer pastas salad dressings seasonings (pure spices are OK, but check seasoning mixes for gluten-containing additives) some herbal teas and flavored coffees soup mixes and canned soups soy sauce and soy sauce solids (they may be fermented with wheat; don't eat them unless you verify they're OK with a dietitian)

91. 92. 93. 94. 95.

spreads, soft cheeses, and dips stuffings thickeners udon noodles wheat-free products (wheat free does not mean gluten free; many wheat-free cookies and breads contain barley or rye flour, which contains gluten and other gluten-containing ingredients) yogurts with wheat starch

Finding Gluten-Free Foods and Ingredients

Most grocery stores carry a few gluten-free products these days. You may be able to find gluten-free bread, cereal, baking mixes, cookies, and crackers at your local market. For a wider selection, make a trip to a health food store. Be aware that lots of natural markets and healthfood stores keep foods in bulk bins. It's not a good idea to use even gluten-free products from these bins because the risk of cross contamination is very high. Many specialty shops online also sell a range of gluten-free products, such as bread, pizza crusts, and pastas. Many regular and online shops even sell gluten-free flour blends that you can use to make your own pancakes and waffles, pizza dough, cookies, and brownies. Eating a gluten-free diet is a lifelong commitment. But if you have celiac disease, you are not alone. Lots of support groups, cookbooks, and websites are dedicated to living a gluten-free life. A word of caution, though: What experts know about celiac disease is developing so rapidly that many books and sites are out of date. To make sure you always have the most current and accurate information, consider joining one of the national celiac organizations. There are even glutenfree summer camps and special support groups just for kids and teens. Reviewed by: Karoly Horvath, MD, PhD Date reviewed: May 2009

http://kidshealth.org/teen/diseases_conditions/digestive/celiac.html#
Nemours Foundation.

Celiac Disease in Children

In Children. The symptoms of celiac disease in children typically become apparent three to five months after first consuming gluten- containing foods although for some few cases, the interval may be as short as one month. Several of the experts on infant feeding advise that solid foods should not be introduced to a babys diet until nearly five months old and that glutencontaining cereal should be avoided for the first six months of life. The celiac, but otherwise normal baby, thrives until gluten is introduced into the diet and then begins to refuse feedings and fails to gain weight. The child may gradually become irritable or listless and develop a large abdomen. The stools will typically become abnormal, perhaps large, pale and offensive, or representative of a loose-like diarrhea. Stools generally float because of the high content of air and fat. The child may also vomit from time-to-time or in some cases exhibit forceful projectile vomiting with the consumption of selected glutencontaining foods. Many children lose weight or have a failure to gain weight and the buttocks become flattened. Some few children may become quite ill with acute diarrhea and dehydration. Symptoms vary and are different from one celiac child to the next with no two being alike in how the condition acts out for them and in their bodies. Older children with more subtle symptoms of poor appetite, poor growth, and anemia are much more difficult to diagnose as there are many other reasons for failure to grow in childhood. Clinical symptoms often diminish or disappear during puberty [adolescence], although biochemical or morphologic abnormalities of the celiac condition may persist. More active symptoms will again reoccur in early adult life following the period when the immune system appears to give more of its

attention to sexual develop- ment. While the teen may feel that he or she has grown out of the disease, the actuality is that the condition continues and should [must] be treated with the same strict gluten-free diet. Symptoms to Expect. Personality changes may occur in children with celiac disease; selected children may become unable to concentrate, be irritable, cranky, and have difficulties with mental alertness and memory function; however, the same process may also occur in teens and adults. Before removal of gluten from the diet, celiac patients may experience selected neuro-psychiatric symptoms including mood changes, irritability, and depression. The celiac parent may need to reduce expectancies in learning, following explicit directions, and in carrying out selected aspects of basic discipline for their celiac child. The damage to the mucosa lining of the small intestine is the same for both children and adults. There appears to be a rapid loss of cell surface with the result, even with increasing cell recovery, it is unable to keep up. The loss of absorptive surface cells of the mucosa of the small intestine results in failure to digest and absorb food from the small intestine into the blood. The concentration of gluten is highest in the upper part of the small intestine, just beyond the duodenum, where the absorption and the damage to the bowel occur. In the person with celiac disease, products derived from wheat, which contain proteins commonly called gluten or gliadin, cannot be digested because of an immunological reaction to the toxic prolamins in these proteins. Products produced from barley, rye, and oats cause the same immune response because their prolamin content has similar amino acid sequences. Wheat, however, is the only grain that contains all of the toxic prolamins. It is from wheat gluten that we have the base nomenclature for the gluten-free diet.

The continued consumption of the toxic prolamins in a person who is affected with celiac disease causes a reaction that destroys the villi in the small intestine [the jejunum], resulting in malabsorption of vitamins, minerals, proteins, amino acids, sugars, and fats. In children, this malabsorption may also cause bone problems because of lack of calcium, varying levels of abdominal distention, vomiting, muscle wasting, and failure to properly grow and develop. Why Celiac Disease in my Child. Celiac disease presents a wide spectrum of symptoms. The three central factors that appear to relate to onset include the following: inheriting the right genes, the appropriate gliadin from a grain protein to cause a toxicity, and the action of the immune system. The genes that determine celiac disease can come from one or both parents in the blood line. In from 2 to 15 percent of families in which one parent has celiac disease, multiple members will have the potential to develop the condition. Most researchers indicate that same family siblings appear to have a 30 to 40 percent risk of developing celiac disease. While the HLA genes are necessary to cause and develop celiac disease, they alone are not sufficient to cause the condition to be activated. The Gluten-Free Diet. Beginning with the diagnosis of celiac disease, it is important to find the best way of helping that child to accept the fact that there are certain foods that he or she cannot eat. Parental and sibling attitudes and the attitudes of friends in the community will be important as well. If family members and friends can accept celiac disease and the diet as a way of life, it will be much easier for the childnow and later in life. The dictates of a strict gluten-free diet can be more easily communicated to children if the emphasis is on what you can have rather than what you cant have. Lists on the refrigerator, having their snack drawer, and a program of gluten-free food items that includes everyone in the family at meal time will be

helpful. Having their lists at restaurants, snack shops, and at school will be supportive and helpful. With a celiac child, the family then becomes a celiac family. For most families, it is typically best if the entire family is on the gluten-free diet. That is not to say there should not be special occasions and specialty foods from time-to-time. If all main dishes can be the same, much of the feeling of being different in the home will be removed. Exceptions are most often breads, cakes, and pastries, but even these staples should be provided for all family members if there can be acceptance and a good attitude. It is important that the child understand as many aspects of the gluten-free diet as necessary for his/her stage in life. The symptoms and difficulties that may be encountered in going off the diet can be dealt with in a simple, straightforward manner. These matters, of necessity and in the interests of self-care, must be handled without threat and without instilling fear or guilt. As the child learns about himself and his/her body, he or she needs also to learn about the digestive system, this particular disease and how to handle it appropriately. Treatment of the Celiac Child. Special needs, special skills, special interests should be treated as such; and, without making the child to feel different or not quite good enough. Attitude and parenting skills on the part of the parents and extended family members will go a long way toward not having the child enter into any aspect of what may be referred to as the sick child syndrome. Since one or both parents may find themselves overextended or overprotective with their own child who has the celiac condition, it is often helpful to review and discuss management practices with the childs pediatrician and the school nurse or counselor. Teach and represent these skills to grandparents, friends, and extended family. Big ears, big feet, having an allergy or diabetes, getting a C in English, and having

celiac disease are all a part of reality and life. Keep them all in their place. Do not help to create nor set yourself up for a poor sick child illness that could be worse [and is typically always worse] than the celiac condition. It is also highly desirable for parents not to become obsessed with symptoms [should they recur], nor to become obsessive about checking stools and questioning behavior at school and away from home. Do not blame every minor illness and infection on the celiac condition. All children become ill; treat minor illnesses as matter-of-factly as possible. If your child should hold onto illnesses such as infections, ear aches, and colds for a longer time and take a longer time to respond to medication and to get back to normal routinesmake it a fun time for being together, for learning and reading together, for sharing with one another. Look for opportunity and you will find it; look for despair and you can find it, too. Encourage your child to accept invitations to parties and dine out as often as reasonable for your household. Simply take along a few gluten-free foods that are appropriate for the occasion and regard that as standard operating procedure. As a parent, make yourself aware of school and holiday functions and be prepared; at times such as Halloween, take treats to the several homes which your child will visit; for holiday and birthday parties, take and provide the appropriate foods for your child. Make some extras so that other interested children might also sample and participate. When guests come to your home or you are hosting parties or after-school snacks for your child, provide gluten-free food for everyone; it will help your child to feel more secure in his or her own home. Eating Out. Do not avoid eating out; obtaining a glutenfree meal in most restaurants and fast food establishments need not be difficult. Fruits, grilled meats, vegetables, salads, eggs, and

potatoes can be staple choices in many locations. Teaching a child how to make wise choices will help him or her to be self-sufficient now as a child and later on as a teen when greater independence is allowed. Look for restaurants that offer the most variety and that have staff members who will take the time to assist with making gluten-free choices. Concentrate on food choices available that you can have rather than sawing through and negating all of the items you cant have. Help your child to develop menu cards for his or her billfold for the restaurants and hotels you visit most often. The name of the restaurant or fast food shop along with four or five appropriate food choices can then be readily available and provide a level of independence that does not then need parental input for each and every visit. Enlist and encourage cooperation and support from chefs and food staff members by expressing your thanks and appreciation for their thoughtful assistance. Consider reminding your child to follow up your good experiences with either a telephone call or a note. At School. For the school system, it will be helpful to have a prescription or letter from the childs pediatric gastroenterologist regarding the diagnosis along with a brief description of the illness and the basic needs for the strict glutenfree diet. A visit with the school nurse to highlight present behavior and present health status, and to learn how best to handle the needs related to the prescription diet in that particular school district will help to develop good connections within the school. It may be possible to develop a team of the physician involved, the school nurse, and the school dietitian or head of the dietary department to consider the needs of the child and how he or she might best fit into the school represented. Woven into the plan of action at school must be helping the child to help himself to move toward independence, selfmanagement, and self-care. Above all the plan must move out of and away from all potential for any child being labeled as a sick

childespecially within the family and in the familys introduction of the child to the school and community. Do not look to the development of a protection system, but to the development of a facilitation program that relates to the needs represented in this student [a student who happens to have celiac disease]. The wise parent will not emphasize differences, problems, what my child cant have, etc. and will then avoid getting onto the trail for the development of the sick child syndrome. If your particular school cafeteria program can not be accommodating to gluten-free food selections, try sack lunches. Hot and cold foods in thermos jars may need to be provided to supplement either a school cafeteria menu or a sack lunch. Packing gluten-free sack lunches for dad or grandpa and enlisting evaluations of food selections from both children and adults can be become a meaningful involvement and brings the prescription diet into the family system. Share with three or four of the commercial food vendors your need to prepare sack lunches. Their dietitians and customer service representatives will come forward with excellent food offerings and sack lunch menu suggestions. In Teens. Most celiac teens will do an excellent job of keeping strictly to the gluten-free diet; a few do not. Those teens who can stay on the prescription diet appear to be able to rise to any challenge and adapt without bother for what could be perceived as any kind or level of health problem. Some teens do have a tough time being different from the crowd. They may have a high need to impress friends in their peer group and also may feel they cannot be different in any way in the eyes of an employer or an authority figure in the school or community. They may need extra encouragement and support and time to discuss their feelings and particular circumstances. Above

all, they must know and gain awareness and understanding that they have a life-long condition for which gluten is harmful. As teens learn to know and understand their bodies and changes which occur, they may need to have assurance from both parents and their monitoring physician regarding the high attention the immune system will be giving to sexual changes and associated body developments. For, it is during these months that it may appear that celiac disease has gone into remission or an even greater myththat they have grown out of the disease. Both of these concepts have no scientific basis. The disease holds forth perhaps with fewer or recognized overt symptoms. Thus, the teen and young adult must be helped to understand that once a celiac, always a celiac is not just a trite or cute saying dreamed up by someone in the medical community. Its a well-researched fact. And, most of allteens and young adults need to maintain a strict adherence to the details of the gluten-free dietnow and for life. High School and College. Dozens of boarding schools, college dormitory systems as well as Big 10/Big 12 as well as schools in the Pacific Rim, and Ivy League have adequate flexibility to handle the gluten-free diet along with any associated specialty needs such as lactose intolerance and specific food sensitivities. These schools and colleges want to help, they like be asked to help and are anxious to do their part if there can be communication regarding the need. So, if the teen will be going away to college and chooses to live within a public system, there is good support and a high interest in dealing with the details of the gluten-free diet. Some colleges will request a prescription from the physician; most schools prefer having special needs regarding diet indicated to them at the time of application for housing. Students who may choose to live off campus but who wish to have some support from the university food services will typically find this service readily available to them. With only a

bit of pre-planning, foresight, and communicationmeeting special dietary needs such as the prescription gluten-free diet will not be a problem for a college or boarding school student. For some celiac patients, the intolerance to gluten appears to heighten periodically and to be close to remission at other times. At this point, there are many case histories and much recorded data, but there appears to be no concrete answers as to why these patterns occur. Most of all, such patterns must not be perceived by the celiac as an active or inactive phase of the disease. The disease continues; its symptoms may be covert, but nevertheless, continue to be the primary illness for the individual. And with the illness in place, the strict gluten-free diet must also continue to be in place. The Gluten-Free Diet for Life. The critical reason for banning gluten for life is that every small particle of gluten may do some damage even though the patient may not be aware of it as a problem at the time. The realization and learning must be: one molecule of gliadin can be as bad as ten thousand. Case history data appears to define that later on in life, the patient who goes on and off the diet or who cheats here and there, is the patient who will run the potential risk of a severe relapse, the addition of other immune-related conditions, or new or related health problems will be introduced. The message is very clearthe basic and cardinal premise for self-management of celiac disease is to avoid all gluten in any and all of its varying formats. Saying no can be the ultimate of self-care.

A Case Study Review

The following case study is found in Pediatric Case Studies, published by Medical Examination Publishing Co., Inc. Garden City, NY. Authored by William M. Liebman, M.D. University of California School of Medicine, San Francisco. pp 178

185.
Questions: 1. Celiac Disease is one of the most common causes of malabsorption in infants and children. Which one of the following is the other most common cause a. Zollinger-Ellison syndrome b. Giardiasis c. Shwachman-Diamond syndrome d. Cystic Fibrosis e. Crohns Disease 2. The possible pathogenetic mechanisms in celiac disease include which of the following? a. Hypergastroenemia b. Hypoperfusion c. Peptidase deficiency d. Infectious [viral] e. Immunologic disorder True of False: 3. Abnormal fecal fat excretion [steatorrhea] is invariably present [95 to100 percent]. 4. The histological features of celiac disease include which of the following?

a. Shortening of villi b. Increased cellularity of lamina propria, predominantly polyps. c. Increased cellularity of lamina propria, predominantly plasma cells. d. Lacteal dilation in lamina propria e. Granuloma formation in submucosa 5. Treatment may include which of the following? a. Gluten-free diet b. Milk-free diet c. Antacids d. Anticholinergics e. Corticosteroids 6. Common complications of this condition include which of the following? a. Crisis b. Peptic ulcer c. Pancreatitis d. Inflammatory bowel disease [Crohns Disease] e. Malignancy

Brief Answers and Comments:

1. [d] Celiac disease and Cystic Fibrosis constitute the most common causes of malabsorption in infants and children. Celiac disease is disorder of the small intestine, producing clinical evidence of malabsorption, characterized by structural [histological] abnormality of the mucosa that is then reversed by gluten withdrawal. The incidence of this condition is significantly higher in Europe than in the United States, i.e., as frequent as 1:300 to 1:500 in western Ireland. More than one member of a family can be affected, e.g., small intestinal mucosal abnormalities in first-degree relatives. In addition, a link has been found genetically, histocompatibility antigens, most notably HL-A8. The likely explanation for this finding rests with immune response genes, which have been linked to the histocompatibility loci in man, as well as in animals. Yet, 20 to 25 percent of patients with celiac disease do not have the HL-A8 antigen. Other HL-A8 antigens have been associated with celiac disease, too, e.g., HL-A1antigen. Therefore, other factors such as environmental and genetic play a role in the development of celiac disease. 2. [c, e] In the 1950s, Dicke initially, others later, observed the association of gluten in the diet with the resultant enteropathy, celiac disease. The consumption of gluten [wheat protein] or one of the ethanol extract fractions, gliadin produces this condition, while their strict dietary elimination results in remission. Acidic peptide products of gliadin, such as fraction IX or alpha gliadin, have been particularly implicated. Two major proposals have been frequently mentioned as the cause[s] of the intestinal lesion upon exposure to gluten or toxic peptides. In the 1980s, the intestinal peptidase deficiency was emphasized. Its theory is based on the lack of an intestinal peptidase, necessary for the detoxification of gluten. Although

peptidase deficiency is present, mucosal injury is also present. This deficiency is more likely secondary to the intestinal lesion because healed mucosa has normal peptidase concentration, suggesting a non-primary nature. The theory that celiac disease is an immunological disorder is the present consideration, especially because of studies with in vitro organ cultures. Biopsy specimens from the small intestine mucosa of normals, patients with gluten enteropathy, and from patients with other intestinal disorders have been studied by this technique. Immunoglobulin synthesis, IgA and IgM antibody with antigluten specificity, was found to be increased only in patients with gluten enteropathy. In addition, IgA complexes have been found in the small intestinal mucosa of patients with gluten enteropathy after gluten challenge. No effect with gluten challenge [protein] was noted in specimens of patients in remission. Therefore, these results suggest that gluten protein must first produce an internal change in tissue integrity of susceptible individuals, e.g., activation of the endogenous effector[s], before toxicity occurs. This hypothesis has been strengthened further by the production of mucosal changes in the presence of gluten protein only when cultured with the mucosa of a patient with active disease. Other aspects of the immune status in gluten enteropathy have been extensively studied. Atrophy of the spleen ahs been confirmed in several reports. Up to a third of patients may be affected. The cause remains undefined. An increase of bloodborn infections is a possibility. Humeral [B-cell] investigations have been numerous. Serum IgG levels has been generally high, while serum IgM levels have usually been low. Elevated, as well as low or normal, serum IgE levels have been reported. Two percent of patients have associated isolated IgA deficiency. Conversely, elevated levels of IgG, IgA, and IgM are usually found in intestinal secretions. Immunocytes [IgA, IgG, IgM] in the intestinal mucosa are increased in number; and increased synthesis of IgA and IgM has been noted in organ

culture experiments. Cell-mediated [T-cell] studies have been numerous, too. Reduced numbers and function of circulating Tcells have been reported, using resetting technique and lymphocyte PHA [pyhtohemagglutinin] responsiveness, respectively. However, clinical evidence of T-cell deficiency has not been observed, e.g., viral/fungal infections. The other choices [the other answers] have not been demonstrated to be present in gluten enteropathy. 3. [f] Steatorrhea [excessive fat excretion] is absent in 10 to 30 percent of children with confirmed celiac disease and is apparently related more to extent than severity of the intestinal mucosal lesion. Usually the 3-day stool fat collection between nonabsorbably markers in untreated celiacs reveals fat excretion over 10 to 15 percent [normal, 5% or less]. Other laboratory studies, including d-xylose absorption, have been performed in the evaluation of possible celiac disease. Both urinary excretion [5 hours] and blood levels should be measured after an oral dose of d-xylose. Some authors have reported the complete separation of untreated celiacs from controls by use of only the fasting and one-hour blood levels. Based on this abnormal value, small intestinal biopsy has or has not been performed. Serum total protein and albumin levels have been decreased in only 50 to 70% of untreated celiacs. In addition, nitrogen losses in stools are abnormally high in only 50%. The cause[s] of the protein abnormalities appears to be abnormal exudation through damaged mucosa, increased cell exfoliation, and diminished amino acid uptake by the damage mucosa. Altered pancreatic functional status, specifically reduced volume, bicarbonate, and enzyme output, is probably related to impaired release of secretin and CCK-PZ [cholecystokininpancreozymin] from damaged small intestinal mucosa. Altered release and/or synthesis of endogenous CCK-PZ also results in

decreased bile delivery and impaired fat absorption. Low serum iron and foliate levels, and less so vitamin B-12, have been found, as have low prothrombin levels. Radiological studies may be helpful. Bone age may be retarded in long-standing, untreated celiacs. Osteoporosis and osteomalacia are not infrequent. Rickets, per se, is not frequent. The classical signs of celiac disease on small bowel series include dilation [jejunum especially], segmentation [large barium clumps with dilated loops], and hypersecretion [flocculation]. In addition, transit time may be slow and diffuse thickening of the mucosal fluids may be visualized. 4. [a, c] The histological features of celiac disease have been well described. The small intestinal tissue is obtained by peroral small biopsy, suing one of several types of biopsy capsules, e.g., Crosby-Kugler. Initially, there is an accelerated rate of enterocyte loss [shedding]. This results in a compensatory increase to the proliferative zone of the intestinal crypts. The mucosal architecture will then be altered when the compensatory effort is inadequate. Subtotal or total atrophy of villi occurs, specifically shortening and clubbing. The crypts become elongated, increased in diameter and tortuous. This produces an alteration in the normal villous-to-crypt ration [over 2:1]. In addition, there is increased cellularity of the lamina propria, predominately plasma cells, less so lymphocytes. Increased collagen may be noted in the subepithelial part of the lamina propria. These changes are particularly prominent in the proximal jejunum. Disaccharidase assay of the involved mucosa has revealed decreased levels, particularly lactase. In addition, decrease alkaline phosphatase, peptide hydrolase, and other enzymes, have also been found. The other answers, granuloma formation, particularly suggestive of granulomatous bowel disease, and lacteal dilation,

suggestive of lymphatic obstruction or disorder, e.g., intestinal lymphangiectasia, are incorrect. 5. [a, b, e] The obvious form of treatment is a gluten-free diet. The initial response is usually dramatic and reasonably rapid, usually within days. The stools become less frequent and more formed, and the appetite and disposition improve. Catchup growth [height, weight] is noted within months. Normal mucosal architecture is usually achieved within 3 to 6 months. Conversely, celiac disease is a permanent condition, and re-introduction of gluten to the diet will be followed by recurrence of mucosal abnormalities. Yet, many authors maintain children on a gluten-free diet for at least 2 years and then reintroduce gluten. Tolerance to gluten is truly a matter of trial and error, requiring careful, continued observation in order to assure adequate appetite, activity, and growth development. These clinical assessments should be substantiated periodically by repeat laboratory tests and repeat peroral intestinal biopsy. If symptomatology reappears or there is a lack of clinical response after 6 months while on a glutenfree diet, repeat evaluation, including intestinal biopsy, is in order. A diagnosis other than celiac disease is likely. Because the disaccharidase of the small intestinal mucosa is frequently reduced in celiac disease, particularly lactase, the corresponding substrates [sugars] should be restricted in the diet. Corticosteroids have produced variable responsiveness, including improved appetite, activity, growth, and decreased stools. Their use has been primarily in more severely affected children and in infrequent crises. Antacids and anicholinergics do not have a place in the usual management. 6. [a, e] Celiac crisis is fortunately uncommon since it is a lifethreatening complication. It may be precipitated by prolonged fasting or intercurrent infection. Dehydration and metabolic

acidosis occur due to the protracted diarrhea and vomiting. Treatment includes nasogastric suction, intravenous fluid therapy, colloid administration if shock or undue hypoproteinemia is present, and usually parenteral corticosteroid administration. With celiac disease in adults, malignancy may develop. Lymphoma of the small intestine is most common but carcinoma of the gastrointestinal tract, such as the esophagus, may develop. Strict adherence to the gluten-free diet does decrease this incidence. The other answers have not been consistently associated with celiac disease.

http://www.e-celiacs.org/2-Celiac_Disease_in_Children.htm