Document resource
Coeliac disease is an autoimmune disorder occurring in genetically susceptible individuals, caused by an abnormal response to gluten. 1 This causes crypt hyperplasia, villous atrophy and epithelial lymphocyte invasion in the small intestine.1 Diagnosis can be made on bloods if IgA tissue transglutaminase (TTG) is over ten times the upper limit of normal with a positive endomysial antibody (EMA) on a second sample, or on duodenal biopsy in those with lower titres.2There is limited literature regarding outcomes for patients with raised TTG who are not subsequently found to have coeliac disease. European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) suggests these children are considered at risk of future coeliac disease and recommend clinical and laboratory monitoring.2 IgA TTG is also known to be associated with other autoimmune conditions including inflammatory bowel disease (IBD), autoimmune liver disease, thyroid disease, type 1 diabetes and with gastrointestinal infection.2We aimed to evaluate alternative causes for raised TTG in patients investigated for coeliac disease in a single tertiary centre and to develop departmental guidelines for management of future cases.Patients undergoing TTG testing under Paediatric Gastroenterology between 2023-2025 were retrospectively identified from the electronic records system. Data was collected on age, symptoms at presentation, history or family history of autoimmunity, infection markers, outcome of endoscopy and subsequent diagnosis.41 patients (25 female, 16 male) had an abnormal TTG result. 21/41 (51%) had a TTG level over ten times the upper limit of normal therefore met no biopsy criteria and were diagnosed with coeliac disease. 20/41 (49%) patients required endoscopy, with 5/20 still awaiting endoscopy. 4/15 (27%) of patients who underwent an endoscopy were diagnosed with coeliac disease on histology, 11/15 (73%) were not found to have coeliac disease on histology.Of those with negative endoscopy, 3/11 (27%) were diagnosed with alternative gastrointestinal pathology (2 with IBD and 1 with helicobacter pylori). 3/11 (27%) patients had existing autoimmune disease (1 with hypothyroidism, 1 with type 1 diabetes and 1 with juvenile idiopathic arthritis). 5/11(45%) had a family history of autoimmune disease (3/5 family history of coeliac disease). 7/11 (64%) were EMA positive, which would indicate potential coeliac disease as per the ESPGHAN guidelines. 5/11 (45%) of patients started a gluten free diet after being reviewed in clinic. Limitations of the study included small patient numbers due to difficulty capturing patients with raised TTG values without coeliac disease from the electronic records system.The majority of children with raised TTG will go on to be diagnosed with coeliac disease, but of those with a negative endoscopy, alternative pathology such as IBD or autoimmune disease should be considered. Literature is limited on long term outcomes for patients with an unexplained raised TTG; we would suggest these children are followed as per ESPGHAN guidelines and repeat endoscopy considered. A departmental guideline is under development currently. Larger studies of patients with raised TTG with negative duodenal biopsy would be helpful to provide more information on outcomes for this group of patients.References Mubarak A, Spierings E, et al. Children with celiac disease and high tTGA are genetically and phenotypically different. World Journal of Gastroenterology 2012 7:19(41):7114–7120.https://www.espghan.org/knowledge-center/publications/Gastroenterology/2019_ESPGHAN_guidelines_for_diagnosing_coeliac_disease. 2020.