Understanding the Natural History of Ehlers-Danlos Syndrome-Hypermobility Type

In a study published in Rheumatology, researchers have described, in detail, the natural history of complaints and disabilities experienced by children diagnosed with joint hypermobility syndrome (JHS)/Ehlers-Danlos-hypermobility type (EDS-HT), and identified the constructs that underlie their clinically functional decline.

The JHS/EDS-HT phenotype generally consists of widespread arthralgia, joint dislocations, soft tissue injuries, deconditioning, muscle weakness, decreased exercise tolerance, proprioceptive deficits, and difficulties with motor skills. The etiology of the disease is believed to be the compromised structural integrity of the connective tissues (including tendons, muscles, and ligaments) as well as most body systems including the skin, eyes, and internal organs.

According to the study, children who have been diagnosed with JHS/EDS-HT and have a high incidence of multi-systemic complaints including orthostatic intolerance, urinary incontinence, diarrhea, poor postural control, and high levels of pain and fatigue at baseline have a significantly higher risk of experiencing a deteriorating trajectory of functional impairment.

Over 3 years, 101 children diagnosed with JHS/EDS-HT were assessed at 3 time points on the following: functional impairment, quality of life, connective tissue laxity, muscle function, postural control, and musculoskeletal and multisystemic complaints. All participants met the following inclusion criteria: were diagnosed with JHS (according to the Brighton criteria) or Ehlers-Danlos syndrome-HT (according to the Villefranche criteria), had a Beighton score ≥4/9; were age 6 to 18 years; were able to adhere to the protocol; and had no trauma or surgery unrelated to JHS/EDS-HT that would interfere with functioning.

Subgroups were categorized by severity of functional impairment (mild, moderate, and severe) via cluster analyses — including their respective clinical profiles — and the differences were assessed using multivariate analysis of covariance. Subsequent trajectories were determined using mixed linear regression models, and the underlying constructs of functional impairment were determined via an exploratory factor analysis.

Analysis of the clinical study showed that functional impairment noted at baseline was predictive of declining trajectories, resulting in decreased walking distance and lower quality of life (P ≤.05) over a 3-year period. The researchers observed multiple interactions between the secondary outcomes, and the 4 underlying constructs that significantly contributed to disability, included: multisystemic effects, pain, fatigue, and loss of postural control (P ≤.046).

Examining the natural history of JHS/EDS-HT will allow a better understanding of the mechanisms influencing the progression of this disease and may allow physicians to identify children who are at high risk, in an effort to prioritize treatment and prevent further functional loss.

Summary & Clinical Applicability

The constellation of symptoms in children with JHS/EDS-HT consists of widespread arthralgia, joint dislocations, soft tissue injuries, deconditioning, muscle weakness, decreased exercise tolerance, proprioceptive deficits, and difficulties with motor skills.

Analysis from this study predicts that multisystemic complaints in these patients (including orthostatic intolerance, urinary incontinence, diarrhea, poor postural control, and high levels of pain and fatigue at baseline) are strongly associated with several maladaptive processes, resulting in decreased walking distance and lower quality of life (P ≤.05) over a 3-year period.

Understanding the mechanisms that influence the progression of this disease may allow clinicians to identify children who are at high risk, in an effort to provide earlier treatment and prevent further functional loss.

Limitations & Disclosures

Regarding the significant impact of postural control on the presented psychological co-morbidity, a limitation of this study includes the influence of family function and interpersonal relationships.

Verity Pacey is a recipient of grant funding by Arthritis Australia and The Menzies Foundation, as well as a travel scholarship recipient by the Rheumatology Health Professions Association. Louise Tofts is a recipient of grant funding by Arthritis Australia. All other authors declare no conflicts of interests.

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Reference

Scheper MC, Nicholoson LL, Adams RD, Tofts L, Pacey V. The natural history of children with joint hypermobility syndrome and Ehlers-Danlos hypermobility type: a longitudinal cohort study [published online April 18, 2017]. Rheumatology (Oxford). doi:10.1093/rheumatology/kex148