Coeliac disease (CD) is a systemic, immune-mediated disorder precipitated by the ingestion of gluten. It is known to manifest at any age after weaning, with an estimated lifetime prevalence of around 1% (Fok et al, 2016). CD is a multisystem disorder presenting with specific gastrointestinal (eg indigestion, diarrhoea, abdominal pain, bloating, gassiness, abdominal distension or constipation) and extra-intestinal manifestations (eg fatigue, dermatitis herpetiformis, anaemia unresponsive to treatment, dental enamel defects, weight loss, faltering growth or delayed puberty) (National Institute for Health and Clinical Excellence (NICE), 2015). Once a diagnosis of CD is confirmed, a lifelong gluten-free diet (GFD) is required with regular monitoring and support. Ingestion of gluten causes an autoimmune response in people with CD, and this leads to damage in the lining of the small intestines and villous atrophy. This causes malabsorption of food nutrients and various clinical manifestations seen in children with CD. This article will provide an overview of the updates on the diagnostic pathways for paediatric CD, and the vital roles that nurses and dietitians can play in its early recognition, diagnosis and management.
Diagnosing coeliac disease
The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) updated their diagnostic guidance for CD in 2012, recommending a no-biopsy pathway (NBP) for symptomatic children (Fok et al, 2016). The NBP is safe in children and has been adopted in Europe and worldwide.
The ESPGHAN guidelines were further revised in 2020 to streamline the diagnostic pathways (Husby et al, 2020). Those modifications are discussed here. The first step for diagnosing CD is serological testing with an immunoglobulin A (IgA) based anti-tissue transglutaminase (TGA-IgA) antibody and is usually performed in primary care when CD is suspected clinically or in screening ‘at-risk’ groups such as type-1 diabetes mellitus (T1DM), first-degree relatives of CD patients, Down syndrome, Turner syndrome etc (Fok et al, 2016; Husby et al, 2020). It is important to remember that one-off negative coeliac serology does not exclude the risk of developing CD later in life.
All children with positive TGA-IgA should be referred to paediatric services and advised not to start a GFD until diagnosis of CD is confirmed by a specialist, even if serology results are positive (NICE, 2015; Husby et al, 2020). This is to maintain strict quality control because CD is a lifelong condition and specialist will decide whether the patient would be diagnosed via a biopsy or the NBP. A ‘specialist’ could be a specialist dietitian, a paediatrician with special interest (SPIN) in gastroenterology, a paediatric gastroenterologist, or a clinical nurse specialist (CNS) with expertise in CD.
No-biopsy pathway
A no-biospsy pathway is required for diagnosing CD in both symptomatic and asymptomatic children (from high-risk groups) who fulfil the following criteria (Husby et al, 2020):
- TGA-IgA ≥10-times upper limit of normal (ULN) (defined for the relevant assay used), and the children are IgA sufficient
- Positive IgA-based anti-endomysial antibodies (EMA-IgA) in a separate second serum sample.
Following the initial positive result, a second separate blood test is performed to confirm the initial high level is correct and ensure there was no anomaly or laboratory error. Where EMA-IgA is not available, the British Society of Paediatric Gastroenterology Hepatology and Nutrition has suggested that a second TGA-IgA ≥10×ULN can be used as an alternative (Murch et al, 2013). It is important to note that the ULN for TGA-IgA will vary across different assays and even for the same assay the local cut-off for ULN may vary (Paul et al, 2017).
Biopsy pathway
For all other children with suspected CD, upper gastrointestinal endoscopy (UGIE) and duodenal biopsy remain mandatory while remaining on a normal gluten-containing diet. This group includes (Husby et al, 2020):
- TGA-IgA <10×ULN (both symptomatic/asymptomatic)
- Asymptomatic children with TGA-IgA ≥10×ULN detected coincidentally while screening for other conditions (ie not from high risk groups)
- Children with IgA deficiency (SIgAD) with suspected CD.
The NICE (2015) guidelines defined IgA deficiency as total IgA <0.07g/L. In patients with SIgAD or a low IgA level (<0.20 g/L), an immunoglobulin G (IgG, based test (deamidated gliadin peptide antibodies (DGP), EMA or TGA) should be performed. The NBP is only applicable to children with TGA-IgA ≥10×ULN and not for those with TGA-IgG >10×ULN. All children with IgA deficiency should undergo UGIE.
Blood tests at initial diagnosis
Children with CD are at an increased risk of malabsorption of key nutrients such as iron, calcium, vitamin D etc because there is risk of poor absorption of these nutrients (NICE, 2015). A UK-wide national survey looking at variations in CD management across specialist gastroenterology centres (n=29) found that most centres do a set of baseline blood investigations, including full blood count, urea and electrolytes, liver function tests, bone profile, thyroid functions tests and vitamin D levels (Paul et al, 2021). We suggest a similar approach to be considered by the specialist while diagnosing CD.
Screening asymptomatic first degree relatives
Health professionals working in primary care should promote and facilitate coeliac screening (IgA level and TGA-IgA) for first-degree relatives (biological parents, full siblings, and offspring) of children diagnosed with CD as there is 10% lifelong chance of developing CD and it should be compulsory for child relatives (Murch et al, 2013). It may, however, be ‘opt-in’ following discussion of pros and cons, especially in asymptomatic adult relatives. Those with positive TGA-IgA results should be advised to remain on a normal diet and then referred to a ‘specialist’ for confirmation of the diagnosis of CD (NICE, 2015; Husby et al, 2020). It is important that serological testing for CD is not offered to infants before gluten has been introduced into their diet (NICE, 2015). It is best to let infants have a normal gluten-containing diet for 6–12 months before a serological testing for CD is requested, but they can be tested sooner if symptomatic.
HLA-DQ2/DQ8 testing
The ESPGHAN (Husby et al, 2020) guidelines state that HLA-DQ2/DQ8 testing (genetic testing) is no longer required for CD diagnosis via NBP (Husby et al, 2020). It may be helpful in some circumstances and this would usually be advised by a SPIN paediatrician or paediatric gastroenterologist (Husby et al, 2020; NICE, 2015). This includes:
- Children who are already on a GFD or have limited gluten ingestion and choose not to (or cannot due to severe symptoms) have a gluten challenge and subsequent UGIE to make a formal diagnosis
- Children with positive CD-specific antibodies, minimal symptoms and non-diagnostic histological changes in duodenal biopsy specimens.
Positive TGA-IgA result coincidentally identified at initial diagnosis of type-1 diabetes mellitus
The NICE (2015) and ESPGHAN (Husby et al, 2020) have not provided any specific recommendations about how to manage this group of asymptomatic children if they are found to have a positive TGA-IgA when screened at initial diagnosis. Several studies have demonstrated that a state of transient positivity of CD serology can occur at T1-DM or thyroid disease diagnosis, which may normalise over time, even when normal diet is maintained (Waisbourd-Zinman et al 2012). Therefore, in the absence of clinical symptoms or signs, and to avoid unnecessary procedures or misdiagnosis and thereby reducing any additional psychological burden (Castellaneta et al, 2015; Unal et al, 2021), we suggest that a repeat TGA-IgA is performed 4–6 months after diagnosis of T1-DM or thyroid disease or sooner if symptoms appear. If serology remains positive, then the coeliac service will discuss the need for endoscopy or initiation of GFD, or repeating the test again; however, this is dependent on the TGA-IgA level and the trend of the result.
Managing coeliac disease
CD is a lifelong diagnosis. At diagnosis it is important that a specialist explains the diagnosis of CD to the family. In communications with the family, the following should promoted (NICE 2015; Fok et al 2016):
- The need for a lifelong GFD must be explained (gluten is found in wheat, rye and barley)
- Current guidance advises to remain oat free for the first 6-12 months or until TGA-IgA levels normalise. As oats are nutritious and present as an ingredient in an increasing number of gluten-free products, some specialists will advise patients/families to include gluten-free oats from diagnosis with restriction only considered if symptoms are ongoing despite good adherence to gluten-free living. In such cases further advice on whether to continue eating gluten-free oats will depend on the child's immunological, clinical or histological response (Murch et al, 2013; NICE, 2015; Paul et al, 2021)
- Practical advice should be given to prevent cross-contamination through maintaining a separate toaster and spreads (to avoid gluten-containing breadcrumbs), separating gluten-free and gluten-containing food stuffs during food preparation, cooking and serving
- Advise to join Coeliac UK to get excellent quality evidence-based information and the additional support that the charity and its advisors can provide.
Expert CD dietitians are skilled in nutritional management and a team approach for follow-up care with specialist CD clinicians is necessary (Stuckey et al, 2009). CNSs also play a key role in CD management in many regions (Paul et al, 2021). It is important that culturally appropriate dietary advice about gluten-free food items is provided to improve adherence to the GFD (Fok et al, 2016). Families need to understand that up to 5% of patients with CD may not tolerate oats—this may be due to the avenin protein or fructans found in oats (Paul et al, 2021).
Children with CD should be reviewed 3–6 months after starting a GFD to assess for dietary adherence. TGA-IgA and any other micronutrient deficiency identified at diagnosis should be repeated at follow-up to ensure normalisation TGA-IgA levels (Murch et al, 2013). Normalisation of TGA-IgA levels can take up to 2 years, however a decrease should be evident if the child is adhering to a strict GFD (Gidrewicz et al, 2017).
Clinical review should be offered to children with CD 1 year following diagnosis. The frequency of follow-up and how that is performed will need to be tailored to how the child and their family are managing. Annual review for CD can be delivered via e-mail, phone, video and face-to-face consultation. However, it should include: measurement of weight and height, review resolution/recurrence of symptoms, assessment of adherence to GFD and investigation into whether there is a need for more specialist dietetic and nutritional advice (NICE, 2015). Studies have shown that children with CD who are lost to follow-up tend to have less well-controlled disease and risk developing complications (Barnea et al, 2014; Blansky et al, 2019).
Immunisation history should be reviewed and pneumococcal vaccination (with PPV23) should be offered post-diagnosis if they have not had this as part of their childhood schedule (Murch et al, 2013; NICE, 2015). Strict adherence to GFD prevents long-term complications such as infertility, osteoporosis, small bowel lymphoma and other autoimmune conditions (NICE, 2015).
Conclusion
Specialist dietitians and CNSs play an increasingly important role in the diagnosis, education and ongoing regular support of CD. They provide advice, improve self-care and help to dispel myths about the condition, thereby facilitating better lifelong adherence to GFD. Enabling children to maintain a GFD is essential for general wellbeing and preventing long-term complications. We hope that this diagnostic update on recent guidelines increases awareness and leads to improved referral for confirmation of diagnosis.
KEY POINTS
- Revised European guidelines allow the option for no-biopsy diagnosis of coeliac disease (CD) in a children with IgA-based anti-tissue transglutaminase titre (TGA-IgA) of ≥10x upper limit of normal (ULN)
- All children with TGA-IgA <10x ULN will still require small-bowel biopsy and histological confirmation while remaining on a normal gluten-containing diet
- National Institute for Health and Care Excellence and the European guidelines recommend that a diagnosis of CD should only be made by a specialist
- Lifelong gluten-free diet is currently the only management available
CPD reflective questions
- Why is it important to be aware of the various manifestations of coeliac disease (CD) and make a referral to a specialist for establishing the diagnosis?
- Nurses and allied health professionals are suitably placed to identify and manage CD. Based on your experience, consider a few challenging scenarios you may have come across of CD and how these were managed
- Nutritional screening can help identify any signs of malnutrition resulting from non-adherence to a gluten-free diet (GFD). Can you identify the various complications that may occur in various age groups in patients with CD?
- Cultural beliefs and dietary practices vary. In your experience, why is it important to understand these differences while recommending a GFD?