Title: Is there a relationship between coeliac disease and Hypermobile Ehlers-Danlos Syndrome (hEDS)?
Funder: Coeliac UK

Abstract: Our group is curious to unfold the relationship between a heritable disorder of connective tissue characterised by hypermobile joints and musculoskeletal symptoms called hypermobile Ehler’s Danlos syndrome (hEDS) and gastrointestinal disorders. Unfortunately, to date, only a single small study has explored the prevalence of coeliac disease (CD) in patients with hEDS. In this study, 31 patients attending a genetics clinic with an established hEDS diagnosis were screened for CD using IgA/G endomysial antibodies and/or anti-tissue transglutaminase, of which six (19%) tested positive. Duodenal biopsies from five had features consistent with CD. The prevalence of CD (16%) in the hEDS group was, therefore, significantly higher than the estimated population prevalence (1%). However, this study has several limitations. First, the population prevalence of CD was estimated rather than calculated. Second, the basis on which hEDS patients were selected for testing for CD was not described and, therefore, there could be a degree of selection bias. Nevertheless, these results broadly corroborate with our preliminary study of a small sample size, in which hEDS was diagnosed in four out of 13 (30%) patients attending GI clinics with a new diagnosis of CD. Recently, Sanders et al. have uncovered an association between CD and postural orthostatic tachycardia syndrome – a frequent autonomic complaint of patients with a diagnosis of hEDS. Together, these three papers suggest a high prevalence of hEDS in patients with CD. Due to a lack of control groups , bias concerns and small sample sizes, studies have systematically failed to conclusively determine whether hEDS is overrepresented in patients with CD. Therefore, it is with excitement that we, in this study, propose filling this knowledge gap by answering the following research question: are CD patients at greater risk of suffering from a hEDS co-morbidity compared to control group subjects without any gastrointestinal disease recruited from a secondary care dermatology clinic? Aims: The primary aim of our study is to determine, using a case-control design, whether hEDS is over-represented in patients with CD (the experimental group) compared to participants recruited from a secondary care dermatology clinic who do not have any gastrointestinal disease (the control group). Secondary aims are to characterise the association between CD and hEDS in greater detail and to determine whether the presence of hEDS in CD is associated with increased comorbidity and reduced quality of life (QOL), and therefore a more severe phenotype. A case-control study design in secondary care will be used to compare the prevalence of hEDS in patients with CD to a control group. A power analysis revealed that 125 subjects are needed in both groups to achieve a power of 80% at a confidence interval of 95%. Participants in the control (n=125) and experimental (n=125) groups will be recruited from secondary-care dermatology and CD clinics, respectively, at a large teaching hospital in London. For the primary aim, structured examinations and interviews to diagnose hEDS in CD and control group subjects will be performed by MFB, who will receive formal training from QA and AF. For the secondary aims, CD patients will be asked to complete validated questionnaires to systematically assess psychopathology (SCL-90), autonomic symptoms (COMPASS), somatic symptoms (PHQ15), and QOL (SF-36). Demographic information and medication histories would be collected via standardised case report forms.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM