Systemic Manifestations and Health-Related Quality of Life in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobility Type

Abstract

Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobility Type (JHS/EDS-HT) is a hereditary connective tissue disorder associated with both musculoskeletal and systemic manifestations. There is increasing recognition of the significance of the non-musculoskeletal manifestations of the disorder, such as fatigue, orthostatic intolerance, gastrointestinal symptoms and psychological features, the presence of which have challenged the historical view of the condition as a “benign” disorder characterised only by musculoskeletal and cutaneous features. The experience of adults affected by JHS/EDS-HT is often defined by delays in the diagnosis of the condition, dissatisfaction with the diagnostic process and symptom management, and the occurrence of a complex array of systemic manifestations associated with the disorder. All of these contribute to a disease morbidity similar to that found in other chronic diseases, significant reduction in overall health-related quality of life (HRQoL) and the progression to functional impairment and disability in some of the adult population affected by the disorder. Over the past three decades, understanding of the disorder has progressed significantly to a point where there is now recognition of the multisystem nature of the condition. There is, however, an ongoing need to further investigate the prevalence, mechanisms and determinants of the systemic manifestations of the condition and the HRQoL experienced by those affected by JHS/EDS-HT. The primary aim of this thesis is to describe the disease profile of JHS/EDS-HT in an adult population, in order to provide future direction for the development of targeted management strategies for adults affected by JHS/EDS-HT. Attention will be focused on investigating the prevalence and significance of non-musculoskeletal features of the disorder and their relationship with the overall HRQoL reported by those affected. The prevalence and factors contributing to the severity of fatigue, psychological manifestations of the condition, and overall HRQoL will be a particular focus of this project. Multiple regression analysis will be used to help further define manifestations of the disorder that are predictive of fatigue severity and HRQoL, in order to inform potential future management strategies for the condition. The aims and objectives of this thesis, a review of the current literature relating to JHS/EDS-HT, and the historical background to the development diagnostic criteria over the past century, are presented in Chapters 1 and 2 of the thesis. To achieve the thesis objectives, two studies were undertaken to investigate the manifestations related to JHS/EDS-HT in an adult population, and specifically to investigate the non-musculoskeletal features of fatigue severity, psychological manifestations of the condition, and overall quality of life experienced by those diagnosed with the JHS/EDS-HT. The investigation of the prevalence, severity and identification of possible predictors of fatigue severity was undertaken as Study 1 and is found in Chapter 3 of this thesis. This study established that significant fatigue was present in 79.5% of participants and was identified as the most prevalent systemic manifestation of the disorder, with the strongest correlation with overall HRQoL of all reported manifestations. This study successfully identified five manifestations contributing to fatigue severity, including four that are potentially modifiable, accounting for 52.3% of the variance in the severity of the fatigue. The modifiable predictors of fatigue severity identified were; current levels of physical activity participation, satisfaction with the diagnostic and management process experienced by individuals, the frequency of reported orthostatic dizziness, and levels of participation in community and personal relationships, in addition to the self- perceived extent of joint hypermobility identified as a non-modifiable feature. The results of this study provide an important evidence base for future research investigating the potential impact of various management strategies targeting these factors identified as contributing to the experience of fatigue in this population. The systemic nature of JHS/EDS-HT and the multitude of manifestations that are associated with the condition have previously been found to be associated with reduced HRQoL in this population. Study 2, which constitutes Chapter 4 of this thesis, aimed to identify the features of JHS/EDS-HT associated with overall HRQoL and to determine if there are modifiable predictors of HRQoL in this population. This study identified three determinants of HRQoL, including; the number of joints affected by pain, the current level of physical activity participation and levels of depressive symptoms reported by participants, together accounting for 54.9% of the variance seen in the reported HRQoL of participants. The results of this study provide future direction for interventional studies undertaken with the aim of improving the overall HRQoL experienced by this population by targeting these modifiable determinants. A summary of the thesis and concluding remarks are presented in Chapter 5. This chapter includes suggestions for future research and clinical interventions in the field of JHS/EDS-HT that have arisen as a result of the 2 included studies.