Maxine Dominique Rouvroye
Over the past decades, our medical perspective on CD has evolved. It is no longer regarded as a rare intestinal disorder characterised by abdominal pain, malabsorption, and diarrhoea, but rather as a common condition with a variety of systemic effects and manifestations. This variety in presentation can make diagnosis difficult. The accuracy with which CD is diagnosed by physicians and its true prevalence within the Netherlands remain uncertain. Chapters 2 and 3 aimed to address these uncertainties. The aim of Chapter 2 was to explore the reported incidence and prevalence of CD in the general practice based on a population-based study. Secondly, we wanted to investigate the general practitioners’ ability to recognise and appropriately diagnose CD. Chapter 3 encompasses a survey and case vignette study among 106 GPs providing insight into the GPs comprehension of CD and its diagnostic process and treatment. Another important question we wanted to address was the occurrence of HLA-DQ7 in HLA-DQ2/8-negative CD. This is an important question for the further development of specific genetic CD tests. Firstly we aimed to compare three commercial kits to single strand conformation polymorphism in Chapter 4. We investigated which HLA-DQ types are detected by the commercial kits and if HLA-DQ7 is also detected. Secondly we compared utilization, and costs. The prevalence of HLA-DQ2/8 negative, but HLA-DQ7 positive CD in The Netherlands is unknown. With Chapter 5, we aimed to elucidate this question and provide insight on the clinical relevance of this HLA-DQ type. Chapter 5 provides data on a cohort of patients typed for HLA-DQ in light of CD screening that were HLA-DQ2/8 negative, but HLA-DQ7 positive. Although gastroduodenoscopy has become optional in some cases in the work up for CD because of antibody testing, a non-invasive test for RCD is yet to be developed. In recent years, an expanding body of evidence has emerged suggesting faecal volatile organic compounds(VOCs) analysis as a diagnostic tool for several gastrointestinal diseases. We aimed to explore VOC analysis as a non-invasive test for RCD II. Chapter 6 contains a pilot study evaluating the use of faecal VOCs analysis as a diagnostic tool for differentiating between CD and RCD II. Finally, there is ongoing debate among patients and within the scientific community concerning neurological symptoms and disorders in CD and non-coeliac gluten sensitivity. Many CD patients experience neurological disorders and ascribe these to CD. Both serological and T-cell–mediated immune responses have been hypothesised to contribute to neurological manifestations; however, histopathological studies remain limited. We aimed to provide an accurate oversight of all existing literature in Chapter 7, a systematic review on neuropathological findings in confirmed gluten-related neurological disorders (GRND). Building upon this body of literature, in Chapter 8 we investigated whether the loss of neurons, especially Purkinje cells, coincides with microglia activation and T- and B-cell infiltration in the cerebellum of patients with CD and a concomitant idiopathic neurological disease affecting the cerebellum. According to some authors, gliadin- and TG6 antibodies represent the key autoantibodies in GRND. In some clinical centres, one or both are included in the diagnostic work-up of unexplained ataxia and neuropathies. In Chapter 9 we addressed the question whether circulating TG6-antibodies are cause or consequence of neurological disorders linked to gluten-sensitivity in a letter in response to a landmark paper on TG6-antibodies in gluten neuropathy. The final question we addressed in this thesis is what the prevalence of gluten-related antibodies is in Dutch patients with idiopathic ataxia and idiopathic neuropathy. Chapter 10 entails a comprehensive analysis of gluten-related antibodies in multiple neurological disorders. With this study we set out to explore the prevalence of GRND in the Netherlands.