Coeliac disease in children

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1 Art & science paediatric nursing Coeliac disease in children Paul SP et al (2015) Coeliac disease in children. Nursing Standard. 29, 49, Date of submission: March ; date of acceptance: March Abstract Coeliac disease is an immune-mediated systemic disorder caused by ingestion of gluten. The condition presents classically with gastrointestinal signs including diarrhoea, bloating, weight loss and abdominal pain, but presentations can include extra-intestinal symptoms such as iron-deficiency anaemia, faltering growth, delayed puberty and mouth ulcers. Some children are at higher risk of developing coeliac disease, for example those with a strong family history, certain genetic disorders and other autoimmune conditions. If coeliac disease is suspected, serological screening with anti-tissue transglutaminase titres should be performed and the diagnosis may be confirmed by small bowel biopsy while the child remains on a normal (gluten-containing) diet. Modified European guidelines recommend that symptomatic children with anti-tissue transglutaminase titres more than ten times the upper limit of normal, and positive human leucocyte antigen (HLA)-DQ2 or HLA-DQ8 status, do not require small bowel biopsy for diagnosis of coeliac disease. Management of the disease involves strict adherence to a lifelong gluten-free diet, which should lead to resolution of symptoms and prevention of long-term complications. Healthcare professionals should be aware of the varied presentations of coeliac disease to ensure timely screening and early initiation of a gluten-free diet. Authors Siba Prosad Paul Specialty trainee year 8, paediatric gastroenterology, Bristol Royal Hospital for Children, Bristol, England. Emily Natasha Kirkham Fourth-year medical student, University of Bristol, Bristol, England. Sarah Pidgeon Specialist paediatric dietitian, Bristol Royal Hospital for Children, Bristol, England. Sarah Sandmann Clinical nurse specialist in paediatric gastroenterology, Bristol Royal Hospital for Children, Bristol, England. Correspondence to: siba_prosad@yahoo.co.uk Keywords Allergy, anaemia, children s nursing, coeliac disease, dietitian, gluten-free diet, human leucocyte antigen, iron deficiency, paediatrics, small bowel biopsy, vitamin D Review All articles are subject to external double-blind peer review and checked for plagiarism using automated software. Online For related articles visit the archive and search using the keywords above. Guidelines on writing for publication are available at: journals.rcni.com/r/author-guidelines COELIAC DISEASE, AN immune-mediated systemic disorder, is elicited by ingestion of gluten and related prolamins in genetically susceptible individuals and is characterised by a variable combination of gluten-dependent clinical manifestations, coeliac disease-specific antibodies, human leucocyte antigen (HLA)-DQ2 or HLA-DQ8 haplotypes and enteropathy (Murch et al 2013). It is caused by the ingestion of gluten, an insoluble plant protein composite found in wheat, rye and barley. Patients present commonly with gastrointestinal symptoms of abdominal pain, persistent diarrhoea and weight loss. However, extra-intestinal features are being recognised increasingly and may cause diagnostic challenge and delay. Healthcare professionals should be aware of the presentations of coeliac disease, when to screen for it and how best to manage the condition. Epidemiology Coeliac disease affects approximately 1% of children (Bingley et al 2004, Murch et al 2013) and the overall incidence in children appears to be increasing (White et al 2013, Whyte and Jenkins 2013). A retrospective cohort study in Scotland recorded a 6.4-fold increase in incidence of coeliac disease from 1990 to 2009 (White et al 2013). Despite greater awareness and improved serological testing, 90% of cases of coeliac disease in children remain unidentified, emphasising the need for early suspicion and increased awareness of the condition (Ravikumara et al 2007). Breastfeeding is considered to have a protective effect. Prolonging the period of breastfeeding and gradually introducing gluten-containing foods in an infant s diet from four months of age was found to lower the risk of developing coeliac disease (Akobeng et al 2006, Steele 2011, Ivarsson et al 2013). Clinical presentation Children with coeliac disease present either symptomatically, with gastrointestinal or extra-intestinal manifestations, or asymptomatically. Classically, the disease presents in children aged six months to two years with gastrointestinal symptoms 36 august 5 :: vol 29 no 49 :: 2015 NURSING STANDARD

2 including diarrhoea, abdominal pain and weight loss. Further gastrointestinal symptoms include bloating, flatulence, vomiting, malabsorption, steatorrhoea and occasionally constipation, as a result of compensatory water absorption in the distal intestine (National Institute for Health and Care Excellence (NICE) 2009, Murch et al 2013, Paul and Spray 2014). Extra-intestinal symptoms of coeliac disease include iron-deficiency anaemia, short stature, faltering growth, liver disease, arthropathy, mouth ulcers, muscle weakness, delayed menarche, dermatitis herpetiformis, dental enamel defects, and osteoporosis and infertility in older people (Mehta et al 2008, NICE 2009, Husby et al 2012, Paul and Basude 2013, Murch et al 2013, Paul and Spray 2014). Asymptomatic coeliac disease may be diagnosed in children who do not have any symptoms of coeliac disease following serological screening for associated conditions or following a diagnosis of coeliac disease in a first-degree relative. Box 1 lists the conditions and familial relations associated with coeliac disease. Healthcare professionals should remain aware of the possibility of coeliac disease in children with any condition listed in Box 1 and should screen for coeliac disease early, particularly since the presentation is commonly asymptomatic or atypical, to prevent a delay in diagnosis. Younger children often present with florid symptoms, such as weight loss, faltering growth, bloated abdomen, diarrhoea or iron-deficiency anaemia, while older school-aged children tend to have more subjective abdominal complaints. These might include, for example, recurrent abdominal pain or delay in puberty (Tanpowpong et al 2012). Diagnosis As part of the diagnosis of coeliac disease, a full history should be carried out, including plotting the height and weight of the child on an age and sex-appropriate growth chart. The clinician should be alert for signs of anaemia, jaundice, mouth ulcers, skin rashes, a distended abdomen and wasting (Paul and Basude 2013). Blood tests including full blood count, liver function tests, urea and electrolytes, fat soluble vitamins and thyroid function test should be performed, particularly bearing in mind the association of coeliac disease with other autoimmune conditions. Parents are advised not to start excluding gluten from children s diet until all investigations have been completed because this would mask symptoms, leading to transient improvement and a negative histological result for coeliac disease, providing false reassurance (Paul and Basude 2013). Diagnosis of coeliac disease is based on symptom recognition, serological screening and small bowel biopsy, using the modified Marsh classification of gluten-induced small intestinal damage (NICE 2009, Murch et al 2013). It is vital that healthcare professionals recognise children with symptoms of, or who have an increased risk of, the disease so that serological testing can be arranged immediately. All children who are symptomatic or are deemed to have a higher risk of coeliac disease should be assessed for the need for serological testing (Box 2) (NICE 2009, Steele 2011, Paul et al 2013, Paul and Spray 2014). Serological screening tests for coeliac disease include total immunoglobulin A (IgA) and IgA-based anti-tissue transglutaminase (anti-ttg) antibodies. Children with a positive anti-ttg titre or a strong suggestion of coeliac BOX 1 Conditions and familial relations associated with a high risk of developing coeliac disease Type 1 diabetes ( 8%). Selective immunoglobulin A deficiency ( %). Down s (5-12%), Williams (8.2%) and Turner s ( %) syndromes. Autoimmune thyroiditis (approximately 15%). Autoimmune liver disease. Unexplained raised transaminases without known liver disease. Dermatitis herpetiformis. Relatives of patients with coeliac disease: First-degree relative (approximately 10%). Human leucocyte antigen (HLA)-matched sibling (approximately 30-40%). Monozygotic twin (approximately 70%). (Adapted from National Institute for Health and Care Excellence 2009, Murch et al 2013) BOX 2 Indications for serological testing to diagnose coeliac disease Chronic constipation. Recurrent unexplained vomiting. Chronic or intermittent diarrhoea. Dental enamel hypoplasia. Dermatitis herpetiformis. Faltering growth. Idiopathic short stature. Prolonged fatigue. Recurrent abdominal pain, cramping or distension. Sudden or unexpected weight loss. Unexplained iron-deficiency anaemia. Autoimmune thyroid disease. First-degree relatives with coeliac disease. Irritable bowel syndrome (excluding diagnosis). Type 1 diabetes. NURSING STANDARD august 5 :: vol 29 no 49 ::

3 Art & science paediatric nursing disease will require further diagnostic procedures, usually a small bowel biopsy to check for signs of enteropathy. It is important to note that children with IgA deficiency will have falsely low anti-ttg levels (the test is IgA based); therefore, screening would fail to identify coeliac disease. IgA levels should be requested at the same time as all other blood tests (NICE 2009). Histological confirmation of coeliac disease after upper gastrointestinal endoscopy and biopsy has been the standard method for diagnosis of coeliac disease (Jenkins et al 2012, Murch et al 2013). However, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommends diagnoses of coeliac disease be made without biopsy if children are symptomatic, have an anti-ttg titre of more than ten times the upper limit of normal and are positive for HLA-DQ2 or DQ8 serotype (Husby et al 2012). Positive blood tests for anti-endomysial antibody (EMA) are also required for a serological diagnosis of coeliac disease (Husby et al 2012). If EMA is not available, a second anti-ttg titre of more than ten times the upper limit of normal can be used as an alternative, as recommended by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) and Coeliac UK (Murch et al 2013). In cases where the anti-ttg titre is raised but is less than ten times the upper limit of normal or in asymptomatic children (irrespective of the level of anti-ttg titre), a biopsy while on a normal gluten-containing diet is required for a diagnosis of coeliac disease (Husby et al 2012, Murch et al 2013). First-degree relatives of children newly diagnosed with coeliac disease should be screened for coeliac disease after appropriate counselling has been given. This should be organised by the GP and occur in primary care settings in the UK. The BSPGHAN and Coeliac UK guidance on continuing serological testing for children from high-risk groups is provided in Table 1. Guidance on gluten challenge for children who may have been started on a gluten-free diet without an established diagnosis of coeliac disease or where doubt remains about the initial diagnosis is included in the recommendations (Husby et al 2012). Differential diagnoses should be considered, including (NICE 2009, Lebwohl et al 2013): Cow s milk protein allergy. Other food allergies, including wheat allergy. Post-enteritis syndrome enquire about recent gastrointestinal infection and monitor for symptom resolution within a few weeks. Crohn s disease generally in older children; look for extra-intestinal features and raised inflammatory markers. Irritable bowel syndrome. Spontaneous bacterial overgrowth in the small intestine. Protein energy malnutrition as a result of poor nutritional intake. Giardiasis check stool microbiology. Hypo-gammaglobulinaemia and/or immunodeficiency. Tropical enteropathy. Histology Coeliac disease causes proximal small bowel enteropathy characterised by loss of intestinal villi. Villous atrophy with crypt hyperplasia and increased intra-epithelial lymphocytes TABLE 1 Challenging situations in diagnosing coeliac disease Asymptomatic children with associated conditions (Box 1) and negative serology. Consider human leucocyte antigen (HLA) typing. If HLA-DQ2 or HLA-DQ8 is positive, continue surveillance and perform endoscopy if the child becomes symptomatic. The optimum frequency for repeat serological screening with anti-ttg titre is unclear but every three years is reasonable if the child remains asymptomatic. If HLA-DQ2 or HLA-DQ8 is negative, development of coeliac disease is highly unlikely. Discontinue regular antibody screening but perform clinical review and serological testing if symptoms suggestive of coeliac disease develop. (Adapted from Murch et al 2013) Timing of gluten challenge in children (already on gluten-free diet with confirmation of diagnosis of coeliac disease or initial diagnosis of coeliac disease is uncertain). Perform gluten challenge at age six or seven years or after pubertal growth is complete. Best managed by increasing gluten within the normal diet, by consuming gluten-containing food. Monitor symptoms and serum anti-ttg antibodies and repeat or perform upper gastrointestinal endoscopy and small bowel biopsies if serology becomes positive. 38 august 5 :: vol 29 no 49 :: 2015 NURSING STANDARD

4 (inflammatory cells) are characteristic of the disease (Figure 1). These changes reduce the absorption of nutrients, fat-soluble vitamins and minerals, resulting in negative health consequences and increased risk of extra-intestinal manifestations such as iron-deficiency anaemia and vitamin D deficiency (Murch et al 2013, Paul and Basude 2013). Management Management of coeliac disease consists of a lifelong gluten-free diet and correction of any other associated medical conditions such as vitamin D deficiency or iron-deficiency anaemia. Irrespective of the pathway (biopsy or serology) that was used to confirm the diagnosis of coeliac disease, children should be offered the same follow up with the paediatrician or paediatric gastroenterologist. A specialist paediatric dietitian should be involved to explain the diagnosis, provide counselling, provide support with the gluten-free diet, ensure adherence and monitor for possible complications (Paul and Spray 2014). Any other abnormalities detected at diagnosis, for example vitamin D deficiency or iron-deficiency anaemia, should be corrected and improvement of symptoms such as faltering growth should be monitored. The gluten-free diet should be initiated by a specialist paediatric dietitian, ideally within one or two weeks of diagnosis of coeliac disease. Children should be followed up at three to six-month FIGURE 1 Normal small intestinal mucosa (a) and villous atrophy in coeliac disease (b) a) intervals in the first year and annually thereafter (Murch et al 2013). Follow-up appointments should monitor growth, check adherence to gluten-free diet and monitor for any delay in onset and progress of puberty, as well as the development of other autoimmune conditions such as type 1 diabetes and hypothyroidism. The clinician should be alert to signs and symptoms that may suggest poor adherence to a gluten-free diet or development of other autoimmune associations during routine clinic visits, including: Increased tiredness (diabetes). Increased toileting and recurrence of bed-wetting in (previously continent) older children (diabetes). Increased thirst (diabetes). Weight loss (diabetes) or excessive weight gain (hypothyroidism). Deterioration in school performance (diabetes, hypothyroidism). New-onset constipation (hypothyroidism). Faltering in height gain (hypothyroidism). Increased physical inactivity or new-onset sedentary lifestyle (hypothyroidism). Serological re-testing should be performed a minimum of six months after commencement of a gluten-free diet to ensure anti-ttg levels have returned to normal (Paul and Spray 2014). Intestinal mucosa and anti-ttg levels will return to normal usually within 12 months of commencement of a gluten-free diet, although it also depends on the initial levels and patients adherence to the gluten-free diet (Husby et al 2012). Compared with physician-led coeliac disease clinics, specialist nurse-led and dietitian-led coeliac disease clinics have been found to be equally effective in managing children with coeliac disease; this option may provide better continuity of care and is also appreciated by families (Rajani et al 2013). b) Role of the paediatric dietitian The dietitian has an integral role in the management of children with coeliac disease. The child and family should receive education from a dietitian about the condition, the role of diet in disease management and the risk of complications that may occur as a result of non-adherence to a gluten-free diet. In addition, the dietitian assesses nutritional status, monitors and helps overcome barriers to adherence to a gluten-free diet and helps achieve a balanced nutritional intake, with a particular focus on meeting the recommended nutrient intake for dietary calcium and other essential nutrients. All dietary recommendations should take into NURSING STANDARD august 5 :: vol 29 no 49 ::

5 Art & science paediatric nursing consideration the cultural beliefs and individual food preferences for each family. Otherwise there is a high risk that adherence to dietary advice may be low (Paul et al 2013). Oats should be eliminated from the diet for the first six months following diagnosis because there is a risk they may be contaminated with other gluten-containing grains, such as wheat, barley or rye, having probably been processed in the same factories. In addition, approximately 5% of patients will cross-react to avenin, the protein in oats, which has a similar structure to gluten. Reintroduction of gluten-free oats under the supervision of a paediatric dietitian is usually advised when the child has become asymptomatic and/or the anti-ttg level has normalised (Murch et al 2013). In rare cases a brief period of lactose-free diet will be necessary as well as a gluten-free diet (Murch et al 2013). This is required if damage caused by coeliac disease to the brush border epithelium has given rise to a secondary lactose intolerance. The lactose-free diet is usually required on a temporary basis and lactose digestion improves when a gluten-free diet is established fully, since the gut is able to heal. Reintroduction of lactose in the diet should be performed gradually and be monitored by the dietitian. Families should be encouraged to join the coeliac disease charity Coeliac UK, because this group can provide comprehensive food and drink information and gluten-free venue guides. Coeliac UK has an expert helpline and has released an app called Gluten free on the move, available through the charity s website (www. coeliac.org.uk). The app can be a useful tool to support compliance and self-management in adolescent patients. Role of healthcare professionals Healthcare professionals in the community have an important role in ensuring that a strict gluten-free diet is adhered to, that gluten-free foods are available on prescription and that schools are aware of the requirement to provide strict gluten-free school meals for children with coeliac disease. The Children and Families Act 2014 came into force in September 2014 and emphasises the need for schools in England to make arrangements for children with medical conditions. GPs have a vital role in supporting the child and prescribing Advisory Committee on Borderline Substances (ACBS)-approved gluten-free staple foods to maximise adherence to the gluten-free diet. GPs should refer to Gluten-free Foods: A Revised Prescribing Guide 2011 (Coeliac UK et al 2011) and should review the prescription provision every three to six months, as dietary needs vary throughout life and to ensure the diet continues to meet the needs of the child. GPs should facilitate serological testing of first-degree relatives of the child, following counselling (Paul and Spray 2014). Nurses working in the community such as school nurses, health visitors and practice nurses can contribute to the early recognition and diagnosis of coeliac disease in children. It is important that school nurses and health visitors are aware of the signs and symptoms of coeliac disease to consider an early referral. They have a vital role in monitoring children, following diagnosis, for resolution of symptoms of coeliac disease and adherence to a gluten-free diet. Frequent school absences and attendance in the school medical room with complaints of abdominal pain and fatigue may be indications of poor adherence to a gluten-free diet. Practice nurses may be consulted for similar symptoms following diagnosis of coeliac disease. References Akobeng AK, Ramanan AV, Buchan I, Heller RF (2006) Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies. Archives of Disease in Childhood. 91, 1, Bingley PJ, Williams AJ, Norcross AJ et al (2004) Undiagnosed coeliac disease at age seven: population based prospective birth cohort study. British Medical Journal. 328, 7435, Coeliac UK, British Dietetic Association, Primary Care Society for Gastroenterology, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (2011) Gluten-free Foods: A Revised Prescribing Guide Coeliac UK, High Wycombe. Husby S, Koletzko S, Korponay-Szabó IR et al (2012) European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. Journal of Pediatric Gastroenterology and Nutrition. 54, 1, Ivarsson A, Myléus A, Norström F et al (2013) Prevalence of childhood celiac disease and changes in infant feeding. Pediatrics. 131, 3, 1-8. Jenkins HR, Murch SH, Beattie RM, Coeliac Disease Working Group of British Society of Paediatric Gastroenterology, Hepatology and Nutrition (2012) Diagnosing coeliac disease. Archives of Disease in Childhood. 97, 5, Lebwohl B, Green PHR, Murray JA, Ludvigsson JF (2013) Season of birth in a nationwide cohort of coeliac disease patients. Archives of Disease in Childhood. 98, 1, Mehta G, Taslaq S, Littleford S, Bansi DS, Thillainayagam A (2008) The changing face of coeliac disease. British Journal of Hospital Medicine. 69, 2, Murch S, Jenkins H, Auth M et al (2013) Joint BSPGHAN and Coeliac UK guidelines for the diagnosis and management of coeliac disease in children. Archives of Disease in Childhood. 98, 10, august 5 :: vol 29 no 49 :: 2015 NURSING STANDARD

6 A failure to request repeat gluten-free prescriptions should raise suspicions about non-adherence to a gluten-free diet, and any such suspicion should be highlighted to the child s medical team. The pneumococcal vaccine is recommended for some patients with coeliac disease because some children are hyposplenic, which increases their susceptibility to pneumococcal infection. Many children already have this vaccination as part of their routine immunisation programme if born in the UK since February It may be recommended for other children on an individual basis after clinical assessment (Murch et al 2013). Prognosis If a gluten-free diet is followed strictly, the prognosis for coeliac disease is good and most children will not develop further complications. Strict adherence to a gluten-free diet allows healing of the intestinal mucosa. While adherence can be problematic in asymptomatic cases, symptomatic children often feel much better within a few weeks of excluding gluten and are likely to appreciate the advantages of a gluten-free diet (Paul and Basude 2013). In children with ongoing symptoms, cross-contamination with gluten in their food should be considered; gluten-free and gluten-containing food should be stored separately to gluten-containing food, and gluten-free food should be prepared using different utensils, for example toasters, baking trays and dough rollers. The risk of not recognising coeliac disease is of persistent gastrointestinal symptoms, impaired nutrition, impaired growth and delayed onset and disordered progression of puberty. Long-term risks include osteoporosis and low bone mineral density, increased risk of pathological fractures, small bowel lymphoma, fertility issues, unfavourable pregnancy outcomes, low birth weight in offspring, spontaneous abortion and development of other autoimmune conditions (NICE 2009, Steele 2011, Paul et al 2013). School nurses, community nurses, dietitians and health visitors should highlight issues of non-adherence or the development of any associated diseases to the paediatrician so that they can be appropriately managed. Children who follow a gluten-free diet have a normal life expectancy without complications from the disease. It is therefore crucial that doctors and nurses remain aware of the possibility of coeliac disease in children so that they are referred for serological testing in a timely manner and to ensure early initiation of a gluten-free diet (Murch et al 2013). Conclusion Coeliac disease is a lifelong condition caused by an immune-mediated reaction to the ingestion of gluten. Improved sensitivity and specificity of serological screening and increased awareness of the condition has led to better identification of coeliac disease. Children suspected of having coeliac disease should undergo serological screening and small bowel biopsy while on a gluten-containing diet to allow the confirmation of a diagnosis. A lifelong gluten-free diet is the only management available, and good adherence to gluten-free diet results in resolution of symptoms and a normal life expectancy. It is essential that affected children are seen by a paediatrician and specialist paediatric dietitian to ensure that the diagnosis, long-term follow up and benefits of adherence to a gluten-free diet are explained properly NS National Institute for Health and Care Excellence (2009) Coeliac Disease: Recognition and Assessment of Coeliac Disease. Clinical guideline No. 86. NICE, London. Paul SP, Basude D (2013) Recognition and management of coeliac disease in children. Journal of Family Health Care. 23, 8, 28-30, Paul SP, Johnson J, Speed HR (2013) Clinical update: coeliac disease in children. Community Practitioner. 86, 1, Paul SP, Spray C (2014) Diagnosing coeliac disease in children. British Journal of Hospital Medicine. 75, 5, Rajani S, Sawyer-Bennett J, Shirton L et al (2013) Patient and parent satisfaction with a dietitian- and nurse-led celiac disease clinic for children at the Stollery Children s Hospital, Edmonton, Alberta. Canadian Journal of Gastroenterology. 27, 8, Ravikumara M, Nootigattu VK, Sandhu BK (2007) Ninety percent of celiac disease is being missed. Journal of Pediatric Gastroenterology and Nutrition. 45, 4, Steele R (2011) Diagnosis and management of coeliac disease in children. Postgraduate Medical Journal. 87, 1023, Tanpowpong P, Broder-Fingert S, Katz AJ, Camargo CA Jr (2012) Age-related patterns in clinical presentations and gluten-related issues among children and adolescents with celiac disease. Clinical and Translational Gastroenterology. 3, e9. doi: /ctg White LE, Merrick VM, Bannerman E et al (2013) The rising incidence of celiac disease in Scotland. Pediatrics. 132, 4, e924-e931. Whyte LA, Jenkins HR (2013) The epidemiology of coeliac disease in South Wales: a 28-year perspective. Archives of Disease in Childhood. 98, 6, NURSING STANDARD august 5 :: vol 29 no 49 ::