Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 29;12(2):170.
doi: 10.3390/children12020170.

The Relationship Between Fatigue, Pain Interference, Pain-Related Distress, and Avoidance in Pediatric Hypermobile Ehlers-Danlos Syndrome

Olivia E Sokol  1 , Emma E Biggs  1 , Ardin S Berger  1   2 , Laura E Simons  1 , Rashmi P Bhandari  1
Affiliations

The Relationship Between Fatigue, Pain Interference, Pain-Related Distress, and Avoidance in Pediatric Hypermobile Ehlers-Danlos Syndrome

Olivia E Sokol et al. Children (Basel). .

Abstract

Background/objectives: Fatigue is a known predictor of disability and reduced quality of life in youth with hypermobility and chronic pain in general. Given the added relationship between chronic fatigue and connective tissue disorders, including hypermobile Ehlers-Danlos Syndrome (hEDS), this study aims to investigate the comparative role of fatigue on important predictors of outcomes for youth with and without hEDS who have chronic pain.

Methods: In this retrospective study, pediatric patients with chronic pain diagnosed with hEDS (n = 100) were compared to an age- and sex-matched group of youth with chronic pain without diagnosed hypermobility (n = 100). Participants completed measures of pain-related distress (PCS-C), avoidance (FOPQ-A), and pediatric PROMIS measures for fatigue, anxiety, and pain interference. Data were analyzed using chi-square tests, t-tests, and ANCOVAs in RStudio.

Results: Fatigue scores were higher and clinically elevated fatigue was more prevalent in those with hEDS than in matched chronic pain peers. Fatigue was significantly positively related to pain interference, avoidance, and pain-related distress in youth with and without hEDS.

Conclusions: The current study supports the need for multidisciplinary treatment and rehabilitation for pediatric chronic pain and hypermobility and suggests that fatigue may be an important factor to consider when treating youth with hypermobility.

Keywords: fatigue; hypermobile Ehlers–Danlos syndrome; hypermobility; pain-related distress; pediatric pain.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PROMIS pediatric fatigue scores in the hEDS and CP groups. Legend: hEDS = group with hypermobile Ehlers–Danlos syndrome; CP = group with chronic pain and no diagnosed hypermobility; Fatigue = PROMIS pediatric fatigue scores.
Figure 2
Figure 2
Association of pain interference and fatigue in hEDS and CP groups. Legend: hEDS = group with hypermobile Ehlers–Danlos syndrome; CP = group with chronic pain and no diagnosed hypermobility; Fatigue = PROMIS pediatric fatigue scores; Pain Interference = PROMIS pediatric pain interference scores.
Figure 3
Figure 3
Association of avoidance and fatigue in hEDS and CP groups. Legend: hEDS = group with hypermobile Ehlers–Danlos syndrome; CP = group with chronic pain and no diagnosed hypermobility; Fatigue = PROMIS pediatric fatigue scores; Avoidance = Child Fear of Pain Questionnaire—Avoidance of Activities Subscale scores.
Figure 4
Figure 4
Association of pain-related distress and fatigue in hEDS and CP groups. Legend: hEDS = group with hypermobile Ehlers–Danlos syndrome; CP = group with chronic pain and no diagnosed hypermobility; Fatigue = PROMIS pediatric fatigue scores; Pain-Related Distress = Pain Catastrophizing Scale for Children scores.
See this image and copyright information in PMC

References

    1. Tinkle B., Castori M., Berglund B., Cohen H., Grahame R., Kazkaz H., Levy H. Hypermobile Ehlers–Danlos syndrome (a.k.a. Ehlers–Danlos syndrome Type III and Ehlers–Danlos syndrome hypermobility type): Clinical description and natural history. Am. J. Med. Genet. Part C Semin. Med. Genet. 2017;175:48–69. doi: 10.1002/ajmg.c.31538. - DOI - PubMed
    1. Steinmann B., Royce P.M., Superti-Furga A. Connective Tissue and Its Heritable Disorders. Wiley-Liss; Hoboken, NJ, USA: 2002. The Ehlers–Danlos Syndrome; pp. 431–523.
    1. Demmler J.C., Atkinson M.D., Reinhold E.J., Choy E., Lyons R.A., Brophy S.T. Diagnosed prevalence of Ehlers–Danlos syndrome and hypermobility spectrum disorder in Wales, UK: A national electronic cohort study and case–control comparison. BMJ Open. 2019;9:e031365. doi: 10.1136/bmjopen-2019-031365. - DOI - PMC - PubMed
    1. Mulvey M.R., Macfarlane G.J., Beasley M., Symmons D.P., Lovell K., Keeley P., Woby S., McBeth J. Modest association of joint hypermobility with disabling and limiting musculoskeletal pain: Results from a large-scale general population-based survey. Arthritis Care Res. 2013;65:1325–1333. doi: 10.1002/acr.21979. - DOI - PubMed
    1. Gensemer C., Burks R., Kautz S., Judge D.P., Lavallee M., Norris R.A. Hypermobile Ehlers–Danlos syndromes: Complex phenotypes, challenging diagnoses, and poorly understood causes. Dev. Dyn. 2021;250:318–344. doi: 10.1002/dvdy.220. - DOI - PMC - PubMed

LinkOut - more resources