Why Can t I Eat Bread?

Why Can t I Eat Bread? Dealing With Celiac Disease In this article: By Flavio Habal, MD, PhD, FRCP 1. What is the investigation? 3. What is the treatment? 4. How do I followup? Case Study A 31-year-old female was referred for assessment of elevated liver enzymes and fatigue. She was six months postpartum. She had no major operations, nor did she have any blood transfusions or any risk factors for infectious hepatitis. She had complained of fatigue for years and had been taking iron supplements. She describes her periods as being normal. She had mild osteoporosis on bone densitometry, and was prescribed calcium, which she did not take. She used to get diarrhea if she drank more than one glass of milk. In addition to fatigue, she had occasional joint pain. She has two healthy children. Both her parents, of European descent, are alive and well. She has a sister with Type I diabetes mellitus. The elevated liver enzymes were felt to be secondary to the hepatic fatty infiltration (hepatosteatosis). In view of the iron deficiency anemia, the slightly decreased albumin and the clubbing, malabsorption was suspected. Hyposplenism has been well documented as a manifestation of celiac disease. Serum immunoglobulin A (IgA) antiendomysial antibody was positive at a dilution of 1/160, highly suggestive of celiac disease. A small bowel biopsy revealed total villous atrophy with crypt hyperplasia and infiltration of the lamina propria by plasma cells, and lymphocytes compatible with celiac disease. Her laboratory results can be found in Table 1. Patient Stats Pale with clubbing. No stigmata of liver disease. Cardiorespiratory system was normal. Abdomen benign. Abdominal and pelvic ultrasound revealed a slightly fatty liver with a small spleen, and no masses were found. Negative serology to Hepatitis A, B, and C. Serum ceruloplasmins for Wilson disease were normal. Screening for autoimmune liver disease with serum antinuclear (ANA), anti-mitochondrial antibody (AMA), and anti-smooth-muscle antibody (SMA), were normal. Immunoglobulin electrophoresis was normal. Find out more on page 38

Table 1 Laboratory Results Patient Normal Range Hemoglobin, g/l 89 120-160 MCV, fl 68 80-95 Leukocytes/L 8.5 x10 9 4.0-10 Platelets 655x10 9 150-400 Blood Film Microcytic, hypochromic, Howell-Jolly bodies Ferritin, µg/l 4.0 20-200 Vitamin B12, ng/l 248 > 180 RBC Folate nmol/l 350 340-1020 AST, U/L 55 9-38 ALT, U/L 89 9-38 A. Phosphatase (ALP), U/L 120 < 100 Albumin g/l 36 > 38 BUN, mmol/l 3.0 3.6-2.1 Creatinine, mmol/l 60 less or equal to 109 MCV = mean corpuscular volume, RBC = red blood cell, AST = aspartate transaminase, ALT = serum alanine aminotransferase, BUN = blood urea nitrogen Dr. Habal is associate professor, University of Toronto and active staff, University Health Network at the Toronto General Hospital, Toronto, Ontario. Celiac disease, also known as celiac sprue, is an autoimmune disease with a protean manifestation. 1,2 It is a genetically inherited condition, resulting in damage to the small intestinal mucosa in response to gluten, which is present in wheat, rye, and barley. Celiac disease is a relatively common condition, affecting one in every 120 to 300 people in Europe and North America. 3 The highest prevalence appears to be in patients from Irish descent, with a rarity in African, Carribean, Chinese, or Japanese individuals. It is also associated with other diseases (Table 2). 82 The Canadian Journal of Diagnosis / April 2003

Celiac disease should be suspected in patients with a persistent iron deficiency anemia who do not respond to supplemental iron, or in patients who have low weight despite a voracious appetite. Patients with this condition may also be stool-occult blood positive, and if a barium enema and an upper gastrointestinal series or gastroscopy is normal, they should be screened for celiac disease. Patients who are undergoing gastroscopy for anemia should have a biopsy of the distal duodenum at the time of the procedure. Type 1 diabetics also have a predisposition and should be screened for this condition, especially in the face of anemia. 4 In females with persistent anemia, despite the fact of menstrual bleeding, there should also be investigation for celiac disease. Abdominal bloating, diarrhea, and steatorrhea with weight loss were classic presentations of celiac disease. They are not as common as had previously been published. It is possible to misdiagnose these patients with irritable bowel syndrome or lactose intolerance. 5 The latter situation may be the result of celiac disease, and may improve with successful treatment of the celiac condition. What is the investigation? Recent serologic developments have resulted in a rapid screening method for celiac disease. A suspected patient who has malabsorption, iron deficiency anemia, and suspicion of celiac disease, should undergo serologic testing. If the tests are positive, then a biopsy from the distal duodenum, obtained at the time of gastroscopy, should be viewed for confirmation. There are different serologic markers, (Table 3). Immunoglobulin A (IgA) antigliadin antibody was com- The Canadian Journal of Diagnosis / April 2003 83

Table 2 Conditions Associated with Celiac Disease Type I Diabetes mellitus Atopic dermatitis Dermatitis herpetiformis Aphthous ulceration Osteopenia Thyroid conditions Abnormal liver enzymes Seizures with cerebral calcification Type I diabetics should be screened for this condition, especially in the face of anemia. monly used, but it had a low specificity, despite the importance of its performance on children less than two-years-old. IgA antiendomysial antibody has high specificity and sensitivity. If a diagnosis of celiac disease is suspected and the test is negative, a serum IgA level should be performed. Unfortunately, the test is expensive. The development of less expensive IgA and immunoglobulin G tissue transglutaminase antibody may replace the other tests. It should be cautioned that the sensitivity of serologic screening may be lower in certain laboratories. It is very rare for a patient to have celiac disease if these serologic tests are negative. What is the treatment? Patient education is extremely important once the diagnosis of celiac disease is established. 6 This condition is a lifelong one which requires lifelong treatment. The treatment is not only aimed at alleviating the present condition, but also at avoiding future complications, which include lymphoma, carcinoma, and osteoporosis. Table 3 Serologic Investigations of Celiac Sensitivity % Specificity % IgA AEA 97-98 98-99 IgA AGA 52-91 85-94 IgG AGA 76-88 88-92 IgA h-ttg 95 94 IgA AEA = immunoglobin A antiendomysial antibody, IgA AGA = immunoglobin A antigliadin antibody, IgG AGA = immunoglobin G antigliadin antibody, IgA h-ttg = immunoglobin A tissue transglutaminase antibody 84 The Canadian Journal of Diagnosis / April 2003

Patients with celiac disease and osteoporosis frequently respond to diet and supplementation treatment with 1,500 mg of calcium and 800 units of vitamin D. Dietary therapy should be started with the assistance of a dietitian experienced in the field. The patient should be given a dietary sheet and instructions. They should be advised to join their local celiac society, which can provide them with valuable information. The Internet has several excellent Web sites for patient information (for the Canadian Celiac Association go to www.celiac.ca). The patient should be started on a gluten-free diet (Table 4), including avoiding products containing wheat, rye, and barley. Pure oats can be safely consumed, but unfortunately, most commercially available oats are contaminated with wheat. The response to gluten-free diets should be closely monitored. Most patients notice significant improvement by three months. It is advisable to repeat the serology at this time, to ensure the patient is adhering to the diet, since persistent serology is suggestive of poor compliance. Osteoporosis and osteopenia are common in patients with celiac disease. Their presence as an unexplained condition should alert physicians to look for The Canadian Journal of Diagnosis / April 2003 85

Table 4 Special Considerations for a Gluten- Free Diet 1.Read food labels carefully and do not use anything that contains the following grains: wheat, rye, barley, oats, buckwheat, millet, amaranth, and quinoa. 2.The following do not contain gluten and can be eaten in any amount: corn, potato, rice, soybeans, tapioca, arrowroot, and carob. 3.Grains are used in the processing of many ingredients, so it will be necessary to seek out hidden gluten. The following terms found in food labels may mean that there is gluten in the product: Hydrolysed vegetable protein (HVP), unless made from soy or corn. Flour or cereal products, unless made with pure rice flour, corn flour, potato flour, or soy flour. Vegetable protein unless from soy or corn. Malt or malt flavouring unless derived from corn. Modified starch or modified food starch unless arrowroot, corn, potato, tapioca, waxy maize, or maize is used. Vegetable gum unless vegetable gums are carob bean gum, locust bean gum, cellulose gum, guar gum, gum arabic, gum aracia, gum tragacanth, xanthan gum, or vegetable starch. Soy sauce or soy sauce solids unless you know they do not contain wheat. Distilled white vinegar is made from grains and may contain gluten. Many commercially prepared condiments are prepared with distilled white vinegar and may contain very small amounts of gluten. 4.Any of the following words on food labels usually means that a grain containing gluten has been used: Stabiliser, starch, flavouring, emulsifier, hydrolysed, plant protein. celiac disease. 7 Screening for osteoporosis with a dual energy X-ray absorptiometry in patients with celiac disease is highly advisable. Repeat densitometry should also be performed after one year to follow their progression. These patients, in addition to following gluten-free diets, frequently respond to treatment with 1,500 mg of calcium and 800 units of vitamin D. Some patients with severe conditions may Take-home message Who should be suspected of celiac disease? Patients with persistent iron deficiency anemia who do not respond to supplemental iron, patients who have low weight despite a voracious appetite, and Type I diabetics in the face of anemia. What s the treatment? Patient education, dietary therapy, gluten-free diet, and repeat serology. 86 The Canadian Journal of Diagnosis / April 2003

benefit from the use of hormone replacement therapy and bisphosphonates. How do I followup? Patients should be seen yearly to evaluate their compliance and their response. Patients who fail to respond, or who experience relapse despite adherence to a strict diet, should undergo repeat small bowel biopsy, a small bowel follow through, and a computed tomography scan, to rule out the development of lymphoma ulcerative jejunoilitis or carcinoma. Patients who comply with the diet have much less risk of developing these complications, hence the importance of the diet. D x References 1. Fasano A, Catassi C: Current approaches to diagnosis and treatment of celiac disease: An evolving spectrum. Gastroenterology 2001; 120:636-51. 2. Ciclitira PG, King AL, Fraser JS: AGA technical review on celiac sprue, American Gastroenterological A s s o c i a t i o n. Gastroenterology 2001; 120:1526-40. 3. Not T, Horvath K, Hill ID, et al: Celiac disease risk in the USA: High prevalence of antiendomysium antibodies in healthy blood donors. Scand J Gastroenterol 1998; 33:494-8. 4. Holmes GK: Coeliac disease and type 1 diabetes mellitus - the case for screening. Diabet Med 2001; 18:169-77. 5. Farrell RJ, Kelly CP: Celiac Sprue. N Engl J Med 2002; 346:180-188. 6. Loftus CG, JA Murray: Celiac Disease: Diagnosis and Management. JCOM 2002; 6:341-349. 7. Vasquez H, Mazure R, Gonzalez D: Risk of fractures in celiac disease patients: A cross-sectional, case control study. Am J Gastroenterol 2000; 95:183-189 Anti-inflammatory analgesic agent. Product Monograph available upon request. General warnings for NSAIDs should be borne in mind. CELEBREX is a registered trademark of G.D. Searle & Co., used under permission by Pharmacia Canada Inc. The Canadian Journal of Diagnosis / April 2003 87