UNDERDIAGNOSIS OF COELIAC DISEASE MODULE 1

UNDERDIAGNOSIS OF COELIAC DISEASE MODULE 1

UNDERDIAGNOSIS OF COELIAC DISEASE MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE Written by: Melissa Wilson BSc (Hons) SRD Coeliac Disease Resource Centre Presented By Dr Schär August 2006 Reviewed by: Dr David S Sanders MD FRCP FACG Consultant Gastroenterologist Hallamshire Hospital Sheffield August 2006 Jacqui Lowdon BSc SRD MSc Paediatric Dietitian Central Manchester and Manchester Children's University Hospitals NHS Trust Manchester August 2006 Updated by: Melissa Wilson BSc (Hons) SRD Coeliac Disease Resource Centre Presented By Dr Schär April 2009 MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE 1

UNDERDIAGNOSIS OF COELIAC DISEASE 2 MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE

CONTENTS CONTENTS FOREWORD PAGE 4 HOW TO USE THIS LEARNING MODULE PAGE 5 LEARNING OUTCOMES PAGE 5 INTRODUCTION PAGE 6 DEFINITION OF COELIAC DISEASE UNDERDIAGNOSIS OF COELIAC DISEASE PAGE 7 CLINICAL PRESENTATIONS OF COELIAC DISEASE PAGE 8 THE COELIAC ICEBERG MODEL TYPES OF COELIAC DISEASE DIAGNOSIS UPDATE PAGE 10 SEROLOGICAL SCREENING TESTS WHICH SEROLOGICAL SCREENING TESTS TO REQUEST? DUODENAL BIOPSY MARSH CLASSIFICATION BENEFITS OF DIAGNOSIS PAGE 14 CLINICAL IMPACT OF DELAYED DIAGNOSIS ANAEMIA OSTEOPOROSIS MALIGNANCY SUMMARY & CASE STUDY PAGE 15 PRACTICE POINTS PAGE 16 REFLECTIVE PRACTICE RECORD PAGE 17 REFERENCES PAGE 18 EVALUATION FORM PAGE 19 MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE 3

FOREWARD FOREWORD As a dietitian or healthcare professional you are likely to come across patients with coeliac disease in your clinical caseload. Depending on your speciality area your experience with this patient group and knowledge of coeliac disease may vary. This learning module focuses on the underdiagnosis of coeliac disease. It has been developed to support you in your clinical practice and to increase your awareness of the underdiagnosis of coeliac disease. It can be used by individuals for continuing professional development (CPD) purposes; by more specialist healthcare professionals, such as specialist gastroenterology dietitians to educate graduate and student dietitians, or as background information for a presentation on the underdiagnosis of coeliac disease to other healthcare professionals. For a presentation on Underdiagnosis of Coeliac Disease please contact Dr Schär Institute on 0800 988 8470 or email:professionals@drschaer.com Module 1: Underdiagnosis of coeliac disease is an evidence-based learning module with a series of directed-learning activities, reflective practice exercises and a case study to complete. There is also some additional reading to undertake to help you understand the background to this topic area. Successful completion of this British Dietetic Association (BDA)-endorsed module can then be used as evidence of CPD, which is a requirement of continued registration with the Health Professions Council (HPC). This learning module is the first in a series of four learning modules. The programme consists of: Module 1: Underdiagnosis of Coeliac Disease Module 2: Coeliac Disease- At-risk Patient Groups Module 3: Understanding the Gluten-Free Diet Module 4: Coeliac Disease, Adherence and the Role of the Healthcare professional 4 MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE

HOW TO USE THIS LEARNING MODULE HOW TO USE THIS LEARNING MODULE All directed learning activities and case studies in this module need to be completed in order to obtain a certificate of completion. Some of the directed learning activities require access to a number of relevant websites in order to obtain information to complete the activity. A copy of this needs to be returned by email to professionals@drschaer.com or printed and posted to the Dr Schar Institute, Dr Schar UK, Units 1-2 Station Court, 442 Stockport Road, Thelwall WA4 2GW. A certificate of completion for the module will then be issued. There is also a section at the back of each module to use as a reflective practice record. This is designed for your own personal continuing professional development activities relating to this topic area. LEARNING OUTCOMES OF MODULE 1 To describe the estimated prevalence of coeliac disease in different populations and appreciate the difference between estimated and actual prevalence figures To describe the various clinical presentations of coeliac disease To use and apply relevant clinical guidelines for the management of coeliac disease for the diagnosis of coeliac disease in clinical practice To identify and be able to discuss the clinical impacts of delayed diagnosis of coeliac disease To be able to formulate a care plan for the appropriate diagnosis of patients with possible coeliac disease To put in action acquired knowledge of this topic area to clinical practice thereby improving clinical care To share information of this topic area with other healthcare professionals through a variety of mediums including discussion and presentations MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE 5

INTRODUCTION INTRODUCTION A range of different healthcare professionals may have input into the clinical care of patients with coeliac disease. However, dietitians have a key role in the management of this patient group as the gluten-free diet is the cornerstone of treatment. This module aims to guide the user through the epidemiology and clinical presentations of coeliac disease as well as directing healthcare professionals to relevant clinical guidelines and an appropriate route of diagnosis. The benefit of diagnosing patients with coeliac disease is also examined. DEFINITION Coeliac disease is an autoimmune gastrointestinal disorder, in which the ingestion of gluten, found in wheat, rye and barley*, results in damage to the small intestine. It is a lifelong condition and can occur at any age in geneticallysusceptible individuals. Immune-mediated damage to the small intestinal mucosa causes villous atrophy and consequently the individual has an impaired ability to digest and absorb food adequately. This leads to malabsorption of essential nutrients such as calcium and iron (as discussed in Module 3 of the learning series). *Oats contain a type of protein that is similar to gluten. Historically, experts were not certain whether or not oats should be included in a gluten-free diet and this subject is still under some discussion. However, the new European Commission (EC) Regulation concerning the composition and labelling of foodstuffs suitable for people intolerant to gluten allows all foods which contain less than 20 parts per million (ppm) of gluten to be labelled as gluten free. This includes pure, uncontaminated oat products. For individual advice, those with coeliac disease should check with their gastroenterologist or dietitian for specific advice on oats. Oats are discussed in more detail in Module 3 of the learning series. 6 MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE

UNDERDIAGNOSIS OF COELIAC DISEASE UNDERDIAGNOSIS OF COELIAC DISEASE Historically, coeliac disease was perceived as a disease of infancy and childhood and thought to be relatively rare. However, in a more recent study, the average age of diagnosis was found to be 44 years in a sample UK population 1. Approximately 25% of newly-diagnosed cases of coeliac disease have been found to occur in adults over 60 years of age 2. Interestingly there is an equal prevalence of coeliac disease in both men and women, however the rate of confirmed diagnosis is thought to be two to three times more common in women. This may be because women are more likely to have to access healthcare before men, for example, a full blood count (revealing anaemia) checked routinely during pregnancy 3,4,5. In 2006, a Coeliac UK survey undertaken amongst approximately 2,000 of its members found that on average it took 13 years, and an average of 13 visits to a GP, to be diagnosed with coeliac disease 6. Whilst traditionally thought of as relatively rare gastrointestinal disorder, with a prevalence of 1 in 1000 in European populations, coeliac disease is now known to be more prevalent than initially thought. The increase in estimated prevalence, established through screening studies, has now led to it becoming one of the most common gastrointestinal disorders in European populations 7, 8. Currently, in the UK, one study suggests only 1 in 8 people with coeliac disease are diagnosed 9. The following directed learning exercise will examine current estimated prevalence rates in various populations. ACTIVITY 1 - Prevalence of Coeliac Disease The following websites will be need to be accessed to complete this activity: Coeliac UK (The National Charity for people with Coeliac Disease) www.coeliac.org.uk The Dr Schär Institute www.drschaer-institute.com 1. Clinical screening studies 10,11 (refer to the clinical library on the Dr Schär Institute website) have shown an estimated prevalence of coeliac disease in both adults and children in the UK population of : a. According to the Coeliac UK website what is the estimated number of people diagnosed with coeliac disease? b. According to the Coeliac UK website how many people have coeliac disease but are not yet diagnosed? c. What is the prevalence of coeliac disease in various ethnic groups? Is it comparable to that in Caucasian populations? (Refer to the Clinical Library on the Dr Schär Institute website) d. Is the presentation of coeliac disease in various ethnic groups comparable that in Caucasian populations? (Refer to the Clinical Library on the Dr Schär Institute website) The improved, and widespread availability, of serological screening tests have contributed to the recognised increase in prevalence of coeliac disease through screening studies 12,13. However, lack of awareness by healthcare professionals of the spectrum of clinical presentation often contributes to a delayed diagnosis. Often patients with only typical symptoms may be formally diagnosed 2, 12. MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE 7

CLINICAL PRESENTATIONS OF COELIAC DISEASE CLINICAL PRESENTATIONS OF COELIAC DISEASE THE COELIAC ICEBERG This model provides a visual aid to help demonstrate the epidemiology of coeliac disease. The tip of the iceberg represents patients who have been clinically diagnosed, usually as a result of a classic presentation of symptoms or a medical practitioner with a good level of awareness and knowledge of coeliac disease. The remaining section of the iceberg represents asymptomatic individuals or those who present with atypical symptoms. One clinical study found that the commonest presenting complaint of coeliac disease was anaemia and subsequently recommended that an endomysial antibody (EMA) test be one of the first line investigations of unexplained anaemia in the community 1. THE COELIAC ICEBERG Typical Coeliac Disease Atypical Coeliac Disease 1% of the Population Activity 2 looks in a little more detail at the various presentations of coeliac disease and can be used as a prompt for reflective practice on patients you have seen in clinical situations. ACTIVITY 2 - Clinical Presentation of Coeliac Disease In the table below note down what you consider typical and atypical symptoms of coeliac disease. References found in the Clinical Library section of the Dr Schär Institute website can be used to help complete this activity. Adults: Typical/Classic Presentation Atypical Presentation Children: Typical/Classic Presentation Atypical Presentation 8 MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE

CLINICAL PRESENTATIONS OF COELIAC DISEASE TYPES OF COELIAC DISEASE TYPICAL COELIAC DISEASE Patients who present in this way have gastrointestinal symptoms. Conventionally this will be chronic diarrhoea, steatorrhoea and weight loss. This occurs in the presence of villous atrophy with a positive antibody profile. ATYPICAL COELIAC DISEASE Patients who present in this way will not have gastrointestinal symptoms. They may present with a number of nonspecific symptoms including anaemia, infertility and lethargy. This also occurs in the presence of villous atrophy with a positive antibody profile. LATENT COELIAC DISEASE This is a rare occurrence. Patients have a positive antibody panel (usuallu EMA) but a normal duodenal biopsy whilst on a gluten-containing diet (or normal diet). However, at some point they may then develop flat or damaged mucosa, which recovers on a gluten-free diet. The misdiagnosis of coeliac disease is common for a variety of reasons, including the changing clinical presentation. A number of studies have found that the range of presenting features of biopsy-proven patients with coeliac disease is varied, with one study finding an absence of diarrhoea and weight loss, two classic presenting symptoms, in approximately 40% of patients at diagnosis 3, 4,14. Delay in diagnosis has potentially serious health implications as discussed later in this module 15. REFLECTIVE PRACTICE Having read and researched the prevalence and various presentations of coeliac disease think about the patients you see in clinic. Choose one of the following sets of questions depending on your outpatient clinic. General Outpatient Clinic Approximately how many patients, diagnosed with coeliac disease do you currently see in your outpatient clinic? Specialist Coeliac Clinic Having reviewed the various presentations of coeliac disease what are the three most common presenting features in your clinic? Does the prevalence rate in your general clinic population correspond with the current estimated prevalence of coeliac disease in the general population? What proportion of your patients with coeliac disease have been identified through screening? Can you think of any patients you are currently reviewing who have a clinical presentation that 'fits' into the presentation spectrum of coeliac disease but who do not have a diagnosis of coeliac disease? Module 2 reviews at-risk groups of patients in more detail. The reflective practice diary at the back of this module provides you with further space to record reflective practice on this topic area. MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE 9

DIAGNOSIS UPDATE DIAGNOSIS UPDATE Once you feel confident that you are aware of the estimated prevalence of coeliac disease, and the spectrum of clinical presentation of coeliac disease, the diagnosis update section takes you through how to ensure an appropriate route of diagnosis is followed. The development of accurate serological screening tests has led to a change in the way coeliac disease is diagnosed. A three-step diagnosis of coeliac disease is now common: i) Identification of at-risk patients (discussed in Module 2) ii) Serological screening tests iii) Definitive diagnosis by intestinal biopsy SEROLOGICAL SCREENING TESTS PRACTICE POINT Ensure patients remain on a gluten-containing diet prior to diagnostic tests to ensure an accurate diagnostic result. Refer to British Society of Gastroenterology (BSG) Guidelines for the management of coeliac disease for quantity of gluten to include in a gluten-containing diet 17. The IgA endomysial antibody (EMA) test has established its role in serological screening tests due to its specificity for coeliac disease, which is close to 100%. Its sensitivity is also approximately 90% 16. However, a negative result may be seen in 2% of people with coeliac disease, who have IgA deficiency. It is therefore important to request a total IgA level at the time of an EMA test 17. In the presence of IgA deficiency an IgG antibody screening test (IgG EMA or IgG ttg) should also be considered 16. Another problem with EMA is that it may not be positive if the degree of small bowel inflammation is less than total (i.e. partial or subtotal villous atrophy) 18. A more recent serological screening test is the enzyme-linked immunoassay (ELISA) for tissue transglutaminase (ttg), now recognised as the autoantigen for the EMA 16. IgG and IgA anti-tissue transglutaminase antibodies are highly sensitive markers and have been found to be present in 90% of patients with untreated coeliac disease 17. WHICH SEROLOGICAL SCREENING TEST TO REQUEST? The sole use of EMA as a screening test for coeliac disease has been shown to underestimate the prevalence of coeliac disease 19. Apart from the problems noted above (with EMA), some individuals may present with negative antibody serology. Other patients may have a positive EMA and a negative ttg result. This may be explained by the differences in sensitivity of the serological tests or the fact that other proteins exist which influence anti-endomysium activity 18,19. FURTHER READING Read the case report included in your module pack, which discusses possible explanations for this 20. The sensitivity of both the EMA and ttg is greater than 90%. However, the ttg is not as specific and positive results have been seen in patients who do not have coeliac disease 16. Many centres now use either EMA or ttg (with a total IgA level), or both. Some centres have a preference to use ttg first as it is a quantative assay (giving a figure or a reading), whilst EMA testing involves subjective interpretation of the test. These centres proceed to EMA testing if the ttg is positive and only then in the presence of a positive EMA do they consider a duodenal biopsy. 10 MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE

DIAGNOSIS UPDATE The inclusion of a recommendation to general practitioners (GPs) to refer all patients with positive EMA and ttg results to a gastroenterologist, on receipt of positive antibody results was found to increase the referral rate 21. This is necessary to confirm the diagnosis of coeliac disease by intestinal biopsy as recommended in the British Society of Gastroenterology (BSG) guidelines 17. DUODENAL BIOPSY Biopsy of the distal duodenum remains the gold standard in the diagnosis of coeliac disease and should be undertaken in all patients thought to have coeliac disease. Even if a patient has a negative antibody profile they could still have coeliac disease although this is uncommon. The progressive damage which occurs in the small bowel has been carefully described by Marsh. A brief summary of the various Marsh classifications is provided below to give an overview and demonstrates the spectrum of severity of inflammation and atrophy in coeliac disease 22. MARSH CLASSIFICATION MARSH 0 LESION This is normal duodenal mucosa (normal villous architecture) with no features of coeliac disease. MARSH I LESION Characterised by normal villous architecture with intraepithelial lymphocytosis, however this may be observed in other clinical conditions such as other autoimmune disorders. MARSH II LESION This resembles the type I lesion but crypt hypertrophy is also present. MARSH III LESION A typically flat mucosa is observed with reduction in height of the villi. Marsh III lesions may be subclassified according to the degree of villous atrophy: IIIA- partial villous atrophy, IIIB- subtotal villous atrophy, IIIC- total villous atrophy. Marsh IV Lesion This describes a rare finding of flat atrophic mucosa due to chronic inflammation. This type of change is thought to be associated with refractory coeliac disease. Refractory Coeliac Disease (RCD) This has been defined as persisting villous atrophy with clinical manifestations in spite of a gluten-free diet for more than 12 months. For further information on RCD visit the Clinical Library section of the Dr Schär Institute website. There are several sets of clinical guidelines in existence, which provide guidance on a recommended route for diagnosis. PRACTICE POINT If a patient has a negative antibody profile including IgA levels- they may still have coeliac disease (antibody negative). For this reason, in the presence of persisting symptoms a biopsy may still be considered. The following activity allows you to examine these in more detail. MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE 11

DIAGNOSIS UPDATE ACTIVITY 3 - Diagnosis of Coeliac Disease Several sets of clinical guidelines exist for the diagnosis and management of coeliac disease: British Society of Gastroenterology (BSG) 17 Primary Care Society of Gastroenterology (PCSG) 23 Working group of the European Society of Paediatric Gastroenterology and Nutrition (ESPGHAN) 24 (The BSG and PCSG guidelines are available on request from the CDRC) National Institute for Health and Clinical Excellence- (NICE) 25 a. What are the clinical investigations recommended by these guidelines for screening and diagnosis of coeliac disease in both adult and paediatric patients? 12 MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE

DIAGNOSIS UPDATE REFLECTIVE PRACTICE Having read the diagnosis update section think about how diagnosis of coeliac disease is carried out in your hospital or GP practice. 1. How is coeliac disease diagnosed in your clinical setting? List the screening and diagnostic tests used and who is responsible for requesting them. 2. Information and test results for diagnosis of coeliac disease should be documented in the medical notes of patients a. Are any other supplementary tests requested at time of diagnosis? If so which tests and why? b. On seeing a newly diagnosed patient with coeliac disease list the background information would you collect at the beginning of the consultation? MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE 13

BENEFITS OF DIAGNOSIS BENEFITS OF DIAGNOSIS The impaired ability to digest and absorb adequate quantities of food, as a result of the villous atrophy, can lead to both minor and major long-term complications. This is particularly the case if diagnosis is delayed for years 12, 15. Unlike many other life-long diseases there is a safe and effective treatment for coeliac disease. The gluten-free diet is the cornerstone for the treatment of coeliac disease and several studies emphasise the importance of both early dietary management and strict adherence to it, in order to help protect patients from complications such as anaemia, osteoporosis, infertility and malignancy disorders 7, 23, 24, 26, 27. CLINICAL IMPACT OF DELAYED DIAGNOSIS OF COELIAC DISEASE This section provides a brief overview of the clinical impact of delayed diagnosis and is looked at in more detail in later modules in this learning series. ANAEMIA A case-finding study found that one of most common modes of presentation of coeliac disease was anaemia 1. The inability to digest and absorb nutrients in undiagnosed coeliac disease leads to an increased likelihood of nutritional deficiencies, including anaemia. The anaemia may be due to iron deficiency or inadequate levels of folate or vitamin B12. OSTEOPOROSIS One of the most common complications of coeliac disease is osteoporosis due to the inadequate absorption of dietary calcium, which contributes to a loss of bone mineral density. As a consequence of delayed diagnosis a large proportion of patients (30-60%) often have osteopenia or osteoporosis (at the time of their diagnosis) due to prolonged calcium malabsorption. Adherence to a gluten-free diet may ensure that their bone mineral density improves or does not become any worse 28, 29. FURTHER READING Nutritional deficiencies in coeliac disease are discussed in more detail in Module 3 MALIGNANCY Previous long-term research has shown those who do not adhere to a gluten-free diet have a two-fold increase in their risk of developing cancer 27. More recent research has shown this association is lower than previously thought. One study showed an increased risk of gastrointestinal cancer and lymphoproliferative disease in patients with coeliac disease compared with controls. In comparison a reduced risk of breast cancer and lung cancer was noted 30. However, for those who strictly adhere to a gluten-free diet for five consecutive years or more, the risk of malignancy is not significantly increased compared with the general population 27, 31. 14 MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE

SUMMARY & CASE STUDY SUMMARY Coeliac disease is a lifelong but manageable condition with a clinically effective treatment. At present screening studies show a higher estimated prevalence of coeliac disease than the number of people actually diagnosed in the UK. A lack of awareness by healthcare professionals may contribute to a delayed or misdiagnosis. The use of serological screening tests offers the possibility of mass screening or case finding of patients with undiagnosed coeliac disease. Module 2 looks in more detail at groups of people who are more at risk of developing coeliac disease. Through identification of at-risk patient groups there is an opportunity for case finding of these undiagnosed patients to be realistically undertaken in clinical practice. CASE STUDY Andrew is a 45-year-old man. He has a long history of general lethargy and abdominal pain and bloating stretching back to his early 30 s. He has maintained a healthy weight throughout this time. He also has an extended history of iron- deficiency anaemia. Repeated visits to his general practitioner (GP) had resulted in a diagnosis of irritable bowel syndrome and he was given some general lifestyle advice. Iron supplements were prescribed for the iron-deficiency and medication to help alleviate his symptoms. A referral to the dietitian for dietary advice on irritable bowel syndrome was also made. On reviewing his medical history and clinical presentation you think there may be a possibility that he has coeliac disease. 1. What tests would you ask the referring GP to carry out and why? a. What advice with regard to his diet would you offer Andrew prior to these tests and why? b. Would you suggest the GP requests any additional blood tests at the time of diagnosis? If so which tests and why? MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE 15

PRACTICE POINTS COELIAC DISEASE IS NOW THOUGHT TO BE THE MOST COMMON MALABSORPTION SYNDROME IN THE UK MODULE 1 PRACTICE POINTS CONSIDER COELIAC DISEASE IN: Men and women All age groups Patients of caucasian and ethnic backgrounds Patients presenting with both classic and atypical symptoms Underweight and overweight patients DIAGNOSING COELIAC DISEASE: Identify at risk patients (refer to Module 2 practice points for further detail) Ensure patient remains on gluten-containing diet prior to diagnostic investigations To screen for coeliac disease request: An EMA test, with IgA level A ttg test At least one IgG test should be included 16 Ensure diagnosis is confirmed via intestinal biopsy Consider additional blood tests to request ROUTE OF INVESTIGATION FOR PATIENTS IN WHOM COELIAC DISEASE IS SUSPECTED 32 All negative Suspicion of coeliac disease (CD) Serologic Tests EMA Total IgA TTG IgG based test Positive result for IgA or IgG EMA +/- anti-ttg Low Probability of CD Intestinal Biopsy Probability of CD If symptons persist further investigation is required Provisional diagnosis of CD Gluten-free diet Repeat biopsy to check mucosal recovery on gluten-free diet Definitive diagnosis of CD 16 MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE

REFLECTIVE PRACTICE RECORD REFLECTIVE PRACTICE MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE 17

REFERENCES REFERENCES 1. Hin H, Bird G, Fisher P, Mahy N, Jewell D. Coeliac Disease in primary care: case finding study. British Medical Journal 1999; 318:164-167 2. Holmes GKT & Catassi C. Coeliac Disease. Clinical Manifestations. Health Press 2000 3. Pare P, Douville P, Caron D, Lagace R. Adult coeliac sprue: changes in the pattern of clinical recognition. J Clin Gastroenterol 1988; 10:395-400 4. Ciacci C, Cirillo M, Sollazzo R, Sabbatini F, Lazzacca G. Gender and clinical presentation in adult celiac disease. Scand J Gastroenterol 1995; 30: 1077-81 5. Green PHR, Stavropoulos SN, Panagi SG, Goldstein SL, McMahon DJ, Absan H, Neugut AL. Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol 2001; 96: 126-31 6. Coeliac UK. Member Survey. 2006 7. Maki M, Collin P. Coeliac Disease. The Lancet 1997; 349: 1755-1759 8. Mearin ML et al. Coeliac disease: is it time for mass screening? Best Practice & Research Clinical Gastroenterology 2005; 19(3): 441-452 9. Van Heel DA and West J. Recent advances in coeliac disease.gut 2006;55:1037-1046 10. West J, Logan RFA, Hill PG, Lloyd A, Lewis S, Hubbard R, Reader R, Holmes GKT. Seroprevalence, correlates and characteristics of undetected coeliac disease in England. Gut 2003; 52: 960-965 11. Bingley PJ, Williams AJK, Norcross AJ, Unsworth J, Lock RJ, Ness AR, Unsworth DJ, Lock RJ, Ness AR, Jones RW. Undiagnosed celiac disease at age seven: population based prospective birth cohort study. British Medical Journal 2004;328:322-323 12. Fasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology 2001;120:636-651 13. Rashid M, Cranney A, Zarkadas M, Graham ID, Switzer C, Case S, Molloy M, Warren RE, Burrows V, Decker Butzner J. Celiac Disease: Evaluation of the Diagnosis and Dietary Compliance in Canadian Children. Pediatrics 2005;116 (6): e754-e759 14. Lo W, Sano K, Lebwohl B et al. Changing presentation of adult celiac disease. Dig Dis Sci 2003; 48 (2): 395-8 15. The role of gluten-free foods in coeliac disease: the evidence. Havard Health Ltd 2002 16. Green PHR. Diagnosis of coeliac disease. Best Practice & Research Clinical Gastroenterology 2005; 19 (3): 389-400 17. British Society of Gastroenterology. Guidelines for the management of patients with coeliac disease. Revised 2002 18. Rostami K et al. Sensitivity of antiendomysium and antigliadin antibodies in untreated coeliac disease: disappointing in clinical practice. Am J Gastroenterol 1999;94(4):888-94 19. Dickey W, Hughes DF, McMillan SA. Reliance on serum endomysial antibody testing underestimates the true prevalence of coeliac disease by one fifth. Scand J Gastroenterol 2000 35(2); 181-321. 20. Sanders DS, Hurlstone DP et al. Antibody negative coeliac disease presenting in elderly people- an easily missed diagnosis. BMJ 2005;330:775-776 21. Sinclair D & Duncan H. What happens to patients with positive tissue transglutaminase and endomysium antibody results in general practice? Journal of Clinical Pathology 2004;57:943-945 22. Marsh M. Gluten, major histocompatibility complex and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('Celiac Sprue'). Gastroenterology 1992;102:330-354 23. Primary Care Society of Gastroenterology. The management of adults with coeliac disease in primary care. 2006 24. Report of Working Group of European Society of Paediatric Gastroenterology & Nutrition. Archives of Disease in Childhood. 1990;65:909-911 25. National Institute for Health and Clinical Excellence. Coeliac Disease-Recognition and assessment of coeliac disease. NICE clinical guideline 86. May 2009 26. Valdimarsson T, Lofma O, Toss G, Strom M. Reversal of osteopenia with diet in adult coeliac disease. Gut 1993;34: S24 27. Holmes, GKT Prior P, Lane MR et al. Malignancy in coeliac disease- effect of a gluten-free diet. Gut 1989;38:322-327 28. McFarlane XA, Bhalla AK, Reeves DE et al. Osteoporosis in treated adult coeliac disease. Gut 1996;36:610-714 29. Holmes GKT. Non-malignant complications of coeliac disease. Acta Paediatr Suppl. 1996;412:68-75 30. West J et al. Malignancy and mortality in patients with coeliac disease: a population-based cohort study. BMJ 2004;329(7468):716-9 31. Mearin LM, Catassi C, Brousse N et al. European multi-centre study on coeliac disease and non-hodgkin lymphoma. Eur J Gastroenterol and Hepatol 2006;18(2):187-194 32. Pietzak MM. Follow-up of patients with celiac disease: Achieving compliance with treatment. Gastroenterology 2005;128:S135-S141 18 MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE

UNDERDIAGNOSIS OF COELIAC DISEASE EVALUATION FORM To enable us to meet your continuing education needs in future resources would you mind taking a few moments to complete this evaluation form. Please place a tick on the line at a point, which most represents your opinion. For example: I would rate my own Continuing Professional Development as being 1 Not Important 2 3 Fairly Important 4 5 Very Important 1. Was this learning unit appropriate to your professional development needs? 1 Not very appropriate 2 3 Appropriate 4 5 Very appropriate 2. Will what you have learned from this module help you in your clinical practice? 1 Not at all 2 3 Some of it will 4 5 Definitely 3. How did you enjoy working through this learning module? 1 Did not enjoy 2 3 No strong feeling 4 5 Really enjoyed 4. Was the support you receieved in completeing this learning module adequate? 1 Insufficient 2 3 Adequate 4 5 Just right Now please complete the following and return by email to professionals@drschaer.com or print and post to the Dr Schar Institute Dr Schär UK, Units 1-2 Station Court, 442 Stockport Road, Thelwall WA4 2GW. Your name: Job Title Work address: Telephone Number: Email: Subscribe to healthcare professional newsletter (please tick): Yes No Thank you. MODULE 1 UNDERDIAGNOSIS OF COELIAC DISEASE 19

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