Exploring pain, fatigue and physical activity in adolescents with Hypermobility Spectrum Disorder or hypermobile Ehlers-Danlos Syndrome

Abstract

Adolescents with Hypermobility Spectrum Disorder (HSD) and hypermobile Ehlers–Danlos Syndrome (hEDS) — two overlapping hereditary connective-tissue disorders characterized by joint hypermobility, chronic pain, impaired body perception, and musculoskeletal symptoms — are the primary focus of this doctoral thesis. Aim: The aim was to better understand pain and its impact on function in activities of daily living in adolescents with HSD/hEDS. Participants: This thesis comprises four studies conducted with three different cohorts of adolescents, including a total of 147 participants. Each cohort consisted of a group of adolescents with HSD/hEDS and a control group of healthy adolescents, in total 67 adolescents with HSD/hEDS and 80 healthy adolescents. Methods: Hypermobility was assessed using the Del Mar Scale (Study I) and the Beighton Scale (Studies II–IV). Balance was evaluated with the Bruininks–Oseretsky Test of Motor Proficiency (Study I). Participation in activities of daily living was measured with the Frequency of Participation Questionnaire, while pain and physical activity were recorded in a diary (Study I). Features of central sensitization, including primary and secondary hyperalgesia, endogenous pain modulation, and exercise-induced hyperalgesia, were measured through experimental pain assessments (Studies II and III). Levels of physical activity were objectively measured using an Axivity AX3 triaxial accelerometer, and sleep patterns were collected with an activity–sleep diary (Study IV). Fatigue was evaluated using the Pediatric Quality of Life Inventory — Multidimensional Fatigue Scale, and pain catastrophizing was assessed with the Pain Catastrophizing Scale — Child version (Studies III and IV). Results: In Study I, it was found that adolescents with HSD/hEDS had significantly more joint hypermobility, experienced greater pain, scored lower on balance tests, and were more affected in their activities of daily living, compared with the control group. Study II demonstrated the feasibility of using experimental pain measurements to investigate underlying pain mechanisms, particularly central sensitization. Study III applied these methods, showing increased general pain sensitivity and a partially reduced pain-inhibitory effect of exercise in adolescents with HSD/hEDS. In Study IV, it was found that adolescents with HSD/hEDS devoted significantly more time to sedentary behavior and less time to moderate-to-vigorous physical activity, and exhibited more nighttime movement, compared with the control group. However, no association was found between fatigue and these activity patterns when pain catastrophizing was controlled for. Conclusions: This thesis highlights that adolescents with HSD/hEDS are significantly impacted in their daily lives, especially in terms of pain, physical activity, and restricted participation in everyday activities. The research suggests a potential connection between HSD/hEDS and central sensitization. It suggests that pain should be understood as a complex issue influenced by central sensitization and biopsychosocial factors. Further, the thesis shows that adolescents with HSD/hEDS are less physically active and exhibit more sleep movements than the control group, which highlights the need for better physical-activity and sleep-health interventions in adolescents with HSD/hEDS. Future research should aim at developing targeted treatments to improve physical activity and alleviate pain in adolescents with HSD/hEDS.