Celiac Disease MONTE E. TROUTMAN, DO, FACOI JANUARY 6, 2016 Objectives Understand the plethora of conditions or symptoms that require testing for Celiac Disease (CD) Develop a knowledge of testing needed to diagnose CD Know the complications of CD Know how to treat and monitor CD Question 1 1.) Testing for celiac disease is reasonable in the following patients? A.) Children with diabetes type 1 B.) Patients with unexplained elevation in ALT and AST C.) Symptomless patients with a first degree relative with CD D.) A, B, C E.) A, B 1
Question 2 Gluten is the storage protein for wheat, rye, and barley. A.) True B.) False Question 3 If you had to pick one serologic test to determine if a patient had CD, which would it be? A.) Human leucocyte antigen testing B.) Anti-Gliadin Antibodies C.) IgA Anti-Tissue Transglutaminase D.) IgM Anti-Tissue Transglutaminase E.) Endomysium Antibody Question 4 Serologic testing and histologic examination is of no use if patient is on a gluten free diet for over one month. A.) True B.) False 2
Question 5 Complications of untreated celiac disease include: A.) Low bone mineral density B.) Lymphomas C.) Infertility D.) Deficient nutritional parameters E.) All of the above Fewer than half of people who should get screen do. Mass screening not appropriate due to limited prevalence. Patients with GI disorders at higher risk. 3
AGA 2006 and ACG 2013 guidelines not followed Underdiagnosed in USA Definition of Celiac Disease Celiac disease is characterized by small intestinal malabsorption of nutrients after the ingestion of wheat gluten or related proteins from rye and barley. Villus atrophy of the small intestinal mucosa, prompt clinical and histologic improvement following strict adherence to a gluten-free diet, and clinical and histologic relapse when gluten is reintroduced. Celiac disease exhibits a spectrum of clinical presentations. Heterogeneous presentation Decrease quality of life Decrease nutritional status 4
Conditions in which Celiac Disease Occurs at Least 2x as Frequently in General Population Abnormal LFTs Chronic iron deficient anemia Dermatitis herpetiformis Diarrhea with weight loss Discolored teeth or developmentally synchronous enamel loss Down and Turner Syndromes Growth failure Incidental discovery of endoscopic or histologic villus atrophy Conditions Continued IBS Metabolic bone disease and premature osteoporosis Oral aphthous ulcers Peripheral neuropathy Postprandial bloating and gas Symptomatic malabsorption Thyroid Disease Weight loss unexplained Infertility 5
Disorders Associated with CD Microscopic colitis Pancreatic exocrine dysfunction Enteropathic associated lymphoma Refractory CD Variants of Celiac Disease Atypical celiac disease is fully expressed gluten-sensitive enteropathy manifest only by extraintestinal symptoms and signs including short stature, anemia, osteoporosis, and infertility. Silent celiac disease is fully expressed gluten-sensitive enteropathy usually found after serologic screening in asymptomatic patients. Note* The atypical and silent variants are more common than classic or typical celiac disease. Variants of Celiac Disease Latent Celiac Disease Patients have normal villus architecture on a gluten-containing diet but, at another time, have had or will have gluten-sensitive villus atrophy. Potential Celiac Disease Patients with potential celiac disease have never had a biopsy consistent with celiac disease but show immunologic abnormalities characteristic for the disease, such as a positive IgA antibody to endomysium or ttg or increased intraepithelial lymphocytes (IELs) in the small intestine These patients often have a genetic predisposition to celiac disease, especially HLA-DQ2, an affected first-degree relative, or both. 6
Variants of Celiac Disease Refractory celiac disease Is also known as unclassified or intractable celiac sprue; is defined as symptomatic, severe small intestinal villus atrophy that mimics celiac disease but does not respond to at least six months of a strict gluten-free diet. Spectrum of Clinical Presentations Interesting History Celiac disease was recognized in the first century AD. The name sprue is derived from the Dutch word sprue, which means aphthous disease, so named because of the high prevalence of aphthous mouth ulcers in these patients. However, that the link between certain cereals and celiac disease was made by a Dutch pediatrician. He became convinced that the consumption of bread and wheat flour was directly responsible for the deterioration in patients suffering from this condition. During World War II, cereals used to make bread were particularly scarce in the Netherlands, and during this time, children with celiac disease improved, only to relapse after the supply of cereal was re-established at the end of the war. It was this serendipitous observation that led to the finding that wheat ingestion exacerbated celiac disease. 7
Epidemiology Celiac iceberg was coined to describe the wide variations in the nature and intensity of clinical presentation of which overt celiac disease is only the emerging peak. The discovery of the large immersed part of the celiac iceberg has transformed the status of celiac disease, long considered a rare disease, particularly in adults, to that of a common health problem. Because we are uncertain of the depth and breadth of the celiac iceberg, the true prevalence of celiac disease remains unknown. Epidemiology The term celiac iceberg was coined to describe the wide variations in the nature and intensity of clinical presentation of which overt celiac disease is only the emerging peak The discovery of the large immersed part of the celiac iceberg has transformed the status of celiac disease, long considered a rare disease, particularly in adults, to that of a common health problem. Because we are uncertain of the depth and breadth of the celiac iceberg, the true prevalence of celiac disease remains unknown. 8
Pathology Celiac disease affects the mucosa of the small intestine; the submucosa, muscularis propria, and serosa usually are not involved. Magnification of the small intestinal mucosal surface in severe untreated celiac disease reveals a flat mucosal surface with complete absence of normal intestinal villi. Histologic examination of tissue sections confirms this loss of normal villus structure. These architectural changes decrease the amount of epithelial surface available for digestion and absorption. Pathology Pathology The exact molecular mechanism by which gluten damages the mucosa has not been established. But more recently Celiac Disease has been considered an immune disorder that is triggered by an environmental agent (gliadin) in genetically predisposed persons. The wide spectrum of clinical manifestations is the result of a complex interplay of varying environmental, genetic, and immune factors. How these control expression of celiac disease and passage from latent to overt disease remains unknown. 9
Clinical Presentation Childhood Difficult to miss Classically, failure to thrive, apathy, irritability, muscle wasting, hypotonia, and abdominal distention. Watery diarrhea or occasionally constipation. Adulthood Diarrhea reported less often, Many have a high BMI and are obese Mean age of presentation in 45 Often extra intestinal manifestations predominate In some there is nothing to suggest there was clinically silent disease an gluten sensitivity came about for the first time in adulthood. Clinical Presentation GI Manifestations Patients with extensive intestinal involvement can have more than 10 stools per day. Because of their high fat content, the stools of patients with celiac disease may be light tan or grayish and greasy in appearance, with a tendency to float and to be difficult to flush from the toilet bowl, this pallor of the stools is reflected in the ancient Latin term diarrhea alba, alba meaning white. Several factors The stool volume and osmotic load delivered to the colon are increased by the malabsorption of fat, carbohydrate, protein, electrolytes, and other nutrients. 10
Clinical Presentation Disease Associations Disease or Finding Prevalence of Celiac Sprue Dermatitis Herpetiformis >90% Diabetes Mellitus Type 1 2-8% Autoimmune Thyroid Disease -3% Down Syndrome 3-12% Turner Syndrome 2-10% Unexplained Infertility 2-4% Unexplained Osteopenia 2-3% Unexplained Anemia 2-8% Irritable Bowel Syndrome Up to 10% Elevated Liver Function Tests 1.5-9% Selective IgA deficiency Up to 8% Diagnosis Laboratory findings in celiac disease, like the symptoms and signs, vary with the extent and severity of the intestinal lesion. Serum IgA EMA or ttg antibody and small intestinal biopsy are the most reliable diagnostic tests for celiac disease. Stool studies, hematologic and biochemical tests, and radiologic studies may be abnormal, but they seldom provide a specific diagnosis because similar abnormalities often are seen in patients with other malabsorptive disease. 11
Diagnosis The current standard of care is a case-finding approach, which targets at-risk subjects such as patients with mild gastrointestinal symptoms, iron deficiency anemia, or IBS-like symptoms, all instances in which the value of serologic testing for celiac disease is accepted widely. Thus, for now, increased awareness of the typical and atypical presentations of celiac disease, coupled with a low threshold for serologic testing in at-risk subjects, can uncover a substantial portion of the submerged iceberg. Diagnosis Almost all patients with celiac disease are positive for HLA DQ2 or DQ8. As a result, HLA testing may be helpful in excluding celiac disease in specific clinical situations, mainly before embarking on a gluten challenge. Although the diagnosis of celiac disease may be suspected on clinical grounds or as a result of abnormal serologic tests, biopsy of the small intestine has remained the standard test to establish the diagnosis. Biopsies usually are performed during endoscopic examination of the upper gastrointestinal tract, an examination that may be indicated for reasons related or unrelated to celiac disease. 12
Diagnosis In the past, gluten challenge discontinuation of the gluten-free diet, followed by repeat biopsy of the small intestine was considered an important confirmatory step in the diagnosis of celiac disease. In current practice, however, gluten challenge is reserved for the few patients in whom the diagnosis remains in doubt after a period of treatment with a gluten-free diet. Gluten challenge is seldom necessary for patients who present with typical signs or symptoms of celiac disease and have documented abnormalities consistent with a celiac lesion on small bowel biopsy. A positive IgA EMA or IgA ttg test before treatment lends further support to the diagnosis of celiac disease and makes a later gluten challenge superfluous. Treatment Gluten Free Diet Principles of Initial Dietary Therapy Avoid all foods containing wheat, rye, and barley gluten. Avoid all oats initially. Avoid malt unless clearly labeled as derived from corn. Use only rice, corn, maize, buckwheat, millet, amaranth, quinoa, sorghum, potato or potato starch, soybean, tapioca, and teff, bean and nut flours. Wheat starch and products containing wheat starch should only be used if they contain less than 20 ppm gluten and are marked gluten free. Read all labels and study ingredients of processed foods. Beware of gluten in medications, supplements, food additives, emulsifiers, or stabilizers. Limit milk and milk products initially if there is evidence of lactose intolerance. Avoid all beers, lagers, ales, and stouts (unless labeled gluten free). Wine, most liqueurs, ciders, and spirits, including whiskey and brandy, are allowed. 13
Treatment Support Groups Key Elements in the Management of Celiac Disease Consultation with a skilled dietitian Education about the disease Lifelong adherence to a gluten-free diet Identification and treatment of nutritional deficiencies Access to an advocacy group Continuous long-term follow-up by a multidisciplinary team Dietary Supplementation Glucocorticoids Differential When Diagnosis of Celiac Disease is Uncertain? Extensive and should include all other causes of villous atrophy besides CD. Other causes of villous atrophy with characteristic histology such as Whipple s disease, collagenous sprue, and eosinophilic enteritis may be excluded by re-review of the intestinal biopsy. A recent travel to or residence history in tropical areas including Southeast Asia, tropical Africa, Central and South America, or the Caribbean islands would increase suspicion of tropical sprue being the underlying cause of persistent symptoms. If additional diseases have been excluded and tropical sprue is a strong consideration, empiric treatment with antibiotics and folic acid would be indicated. Autoimmune enteropathy (AIE), collagenous sprue Whipple s disease could be additional potential etiologies, though these diseases are less common. 14
Refractory Celiac Disease Refractory celiac disease, also known as unclassified or intractable celiac disease defined as symptomatic, severe small intestinal villous atrophy that mimics celiac disease but does not respond to at least six months of a strict gluten-free diet and is not accounted for by other causes of villus atrophy or overt intestinal lymphoma. Refractory celiac disease is uncommon in adults, extremely rare in children, and largely a diagnosis of exclusion Symptoms can persist in treated celiac disease patients for a variety of reasons Should be a diagnosis of exclusion in all patients who have NRCD (non responsive Celiac Disease Question 1 1.) Testing for celiac disease is reasonable in the following patients? A.) Children with diabetes type 1 B.) Patients with unexplained elevation in ALT and AST C.) Symptomless patients with a first degree relative with CD D.) A, B, C E.) A, B Question 2 Gluten is the storage protein for wheat, rye, and barley. A.) True B.) False 15
Question 3 If you had to pick one serologic test to determine if a patient had CD, which would it be? A.) Human leucocyte antigen testing B.) Anti-Gliadin Antibodies C.) IgA Anti-Tissue Transglutaminase D.) IgM Anti-Tissue Transglutaminase E.) Endomysium Antibody Question 4 Serologic testing and histologic examination is of no use if patient is on a gluten free diet for over one month. A.) True B.) False Question 5 Complications of untreated celiac disease include: A.) Low bone mineral density B.) Lymphomas C.) Infertility D.) Deficient nutritional parameters E.) All of the above 16
References Celiac Foundation. Celiac.org Celiac Support Association. csaceliacs.org Diagnosed and Management of Celiac Disease. Am J Gastroenterology 2013, 108: 656-676 17