Ehlers-Danlos syndrome hypermobility type a. k. a. joint hypermobility syndrome (JHS/EDS-HT) is a hereditary musculoskeletal disorder associating generalized joint hypermobility with chronic pain. Anecdotal reports suggest a prominent role for
Ehlers-Danlos syndrome (EDS) is an umbrella term for various hereditary connective tissue disorders (HCTDs) mainly characterized by congenital joint hypermobility, skin hyperextensibility, and tissue fragility. Among the six major forms [
Pain and fatigue are considered relevant determinants of disability in JHS/EDS-HT [
Chronic musculoskeletal conditions, predominantly characterized by chronic pain, are often associated with fear [
In this study, we carried out a questionnaire on 42 JHS/EDS-HT patients in order to evaluate the presence and severity of
All patients studied have attended a multidisciplinary service dedicated to HCTDs and were followed into the “joint hypermobility” outpatient clinic in the Division of Physical Medicine and Rehabilitation of the Umberto I University Hospital (Rome, Italy) and into the clinical genetics outpatient clinic at the Medical Genetics of the San Camillo-Forlanini Hospital (Rome, Italy). Diagnosis was based on published diagnostic criteria including the Brighton criteria for JHS [
General characteristics.
Characteristic | Frequency |
% |
---|---|---|
Gender (female/male) | 40/2 | 95.2/4.8 |
Positive family history | 19 | 45.2 |
Contortionism in pediatric age | 35 | 83.3 |
Motor delay/clumsiness | 9 | 21.4 |
Residual joint hypermobility (Beighton ≥4) | 31 | 73.8 |
Recurrent (≥3) joint dislocations | 31 | 73.8 |
Recurrent (≥3) soft tissue lesions | 18 | 42.8 |
Chronic back pain | 33 | 78.6 |
Chronic arthralgias | 35 | 83.3 |
Chronic myalgias | 36 | 85.7 |
Chronic fatigue | 37 | 88.1 |
Recurrent headaches | 32 | 76.2 |
Unrefreshing sleep | 31 | 73.8 |
Impaired memory/concentration | 24 | 57.1 |
Velvety/smooth skin | 31 | 73.8 |
Hyperextensible skin | 11 | 26.2 |
Easy bruising | 29 | 69.0 |
Eyelid ptosis | 17 | 40.5 |
Varicose veins/hemorrhoids | 7 | 16.7 |
Hernias | 2 | 4.8 |
Uterine/vesical/rectal prolapse | 4 | 9.5 |
In order to evaluate kinesiophobia, pain, and fatigue, all patients were asked to fill in a series of questionnaires including the Tampa Scale Italian version (TSK-I) [
TSK-I is the most widely used questionnaire to assess pain and pain-related fear of movement in subjects with musculoskeletal complaints [
FSS is a scale quantifying fatigue intensity, which has been used in different chronic conditions, such as multiple sclerosis and systemic lupus erythematosus [
NRS is a rapid-to-administrate 11-point numeric scale used to roughly measure any kind of pain with a score ranging from 0 (no pain) to 10 (acute pain).
The Medical Outcome Study 36-item Short-Form Health Survey (SF-36) is a multipurpose, short form health survey to evaluate aspects of health most closely related to quality of life with 36 questions that measure 8 conceptual domains: physical functioning, physical limitation, bodily pain, general health, vitality, social functioning, emotional limitation, and mental health. The raw scores in each domain are transformed into 0 to 100 scale with higher scores indicating better quality of life [
Statistical analysis was conducted with the SPSS software package for Windows, version 19.0. The Kolmogorov-Smirnov probability test was used to assess the normality of the distributions. The FSS mean score was compared with normal healthy adult scores extracted from Krupp et al. [
The Spearman bivariation analysis was conducted in order to test independent variables related to dependent ones. Variables assumed as independent included age, sex, Beighton scores, FSS mean scores, the four subscores of MFI-20, the NRS mean scores, and the SF-36 in all subforms, while TSK-I, TSK-AA, and TSK-H scores were considered
Forty-two patients (40 females and 2 males; mean age at evaluation: 32.80 ± 13.23 years) were selected. Clinical characteristics of the patient samples are summarized in Table
Rough data of the Beighton score, TSK-I, MFI-20, FSS, NRS (pain), and FS-36.
Variable | Mean ± SD (range) |
---|---|
Beighton score |
|
TSK-I |
|
TSK-AA |
|
TSK-H |
|
MFI-20, GF |
|
MFI-20, PF |
|
MFI-20, RA |
|
MFI-20, RM |
|
MFI-20, MF |
|
FSS |
|
NRS (pain) |
|
SF-36, PF |
|
SF-36, RP |
|
SF-36, BP |
|
SF-36, GH |
|
SF-36, VT |
|
SF-36, SF |
|
SF-36, RE |
|
SF-36, MH |
|
BP: bodily pain; FSS: Fatigue Severity Scale; GF: general fatigue; GH: general health; MF: mental fatigue; MFI: Multidimensional Fatigue Inventory; MH: mental health; NRS: Numeric Rating Scale; PF (SF-36): physical functioning; PF (MFI-20): physical fatigue; RA: reduced activity; RE: role-emotional; RM: reduced motivation; RP: role-physical; SF: social functioning; SF-36: short form 36; TSK-AA: Tampa Scale activity avoidance; TSK-H: Tampa Scale harm; TSK-I: Tampa Scale total score; VT: vitality.
Results of the Spearman bivariation analysis comparing TSK-I, TSK-AA, and TSK-H values (as dependent variables) with different variables.
Variable | TSK-I | TSK-AA | TSK-H |
---|---|---|---|
Age | −0.79 ( |
−0.267 ( |
0.146 ( |
Beighton score | −0.66 ( |
0.022 ( |
−0.109 ( |
NRS | 0.013 ( |
0.068 ( |
0.005 ( |
FSS | 0.558 ( |
0.573 ( |
0.388 ( |
MFI-20, GF | 0.323 ( |
0.342 ( |
0.226 ( |
MFI-20, PF | 0.289 ( |
0.335 ( |
0.209 ( |
MFI-20, RA | 0.227 ( |
0.382 ( |
0.064 ( |
MFI-20, RM | 0.057 ( |
−0.022 ( |
0.183 ( |
MFI-20, MF | 0.438 ( |
0.498 ( |
0.250 ( |
SF-36, PF | −0.187 ( |
−0.191 ( |
−0.130 ( |
SF-36, RP | −0.170 ( |
−0.182 ( |
−0.111 ( |
SF-36, BP | −0.103 ( |
−0.700 ( |
−0.109 ( |
SF-36, GH | −0.47 ( |
−0.160 ( |
0.087 ( |
SF-36, VT | −0.323 ( |
−0.293 ( |
−0.266 ( |
SF-36, SF | −0.222 ( |
−0.213 ( |
−0.169 ( |
SF-36, RE | −0.109 ( |
−0.202 ( |
0.02 ( |
SF-36, MH | −0.379 ( |
−0.351 ( |
−0.303 ( |
Significant
BP: bodily pain; FSS: fatigue severity scale; GF: general fatigue; GH: general health; MF: mental fatigue; MFI: multimensional fatigue inventory; MH: mental health; NRS: numeric rating scale; PF (SF-36): physical functioning; PF (MFI-20): physical fatigue; RA: reduced activity; RE: role-emotional; RM: reduced motivation; RP: role-physical; SF: social functioning; SF-36: short form 36; TSK-AA: Tampa Scale activity avoidance; TSK-H: Tampa Scale harm; TSK-I: Tampa Scale total score; VT: vitality.
Multivariate linear regression analysis using the Backward elimination stepwise method.
Variable | TSK-I | TSK-AA | TSK-H |
---|---|---|---|
Age | −0.43 ( |
−0.06 ( |
0.023 ( |
Sex | 0.734 ( |
0.986 ( |
−0.498 ( |
FSS | 1.999 ( |
1.075 ( |
0.927 ( |
MFI-20, GF |
−0.101 ( |
−0.090 ( |
−0.045 ( |
MFI-20, PF | 0.15 ( |
0.09 ( |
0.03 ( |
MFI-20, RA | −0.05 ( |
0.157 ( |
−0.184 ( |
MFI-20, MF | 0.05 ( |
0.087 ( |
−0.034 ( |
SF-36, MH | −0.043 ( |
−0.20 ( |
−0.021 ( |
SF-36, VT | −0.007 ( |
0.007 ( |
−0.018 ( |
|
0.637 | 0.368 | 0.253 |
Significant
FSS: fatigue severity scale; GF: general fatigue; MF: mental fatigue; MFI: multimensional fatigue inventory; MH: mental health; PF: physical fatigue; RA: reduced activity; SF-36: short form 36; TSK-AA: Tampa Scale activity avoidance; TSK-H: Tampa Scale harm; TSK-I: Tampa Scale total score; VT: vitality.
Correlation between Fatigue Severity Scale (FSS) and kinesiophobia as total score TSK-I (a) and in the activity avoidance TSK-AA (b) and in the harm TSK-H (c) subscales.
Pain-related fear is a particular characteristic of patients with musculoskeletal disorders [
Overall, the present study, conducted through a questionnaire-based investigation into 42 patients, in which there is a preponderance of females described as characteristic in JHS/EDS-HT even if the mechanism underlying is unknown [
Conversely,
This study demonstrates once more the urgent need for evaluating and treating JHS/EDS-HT patients within multidisciplinary teams comprising a variety of specialists (who can focus on pain and fatigue) including physiatrists, physical and occupational therapists, clinical psychologists, neuropsychologists, pain specialists, and rheumatologists. In fact, the classic approach of treating JHS/EDS-HT-related pain based on a combination of physical therapy and adjuvant pharmacologic support should be associated with and, hopefully, substituted, at least in terms of prevention, by regular physical exercise and cognitive therapies. Various studies have demonstrated that exercise and fitness are beneficial in a biomedical sense of maturation, strengthening, and healing of bones, tendons, and muscle, while deconditioning refers to a progressive process of worsening physical fitness as reduced muscular activity [
An individualized, modified, and therapeutic programme involving a multidisciplinary team is recommended to prevent chronic pain and deconditioning and thereby reduce suffering in JHS/EDS-HT patients.
The authors declare that no conflict of interests exists concerning this paper and no financial support or other benefits are correlated to this work.
The authors would like to thank Ellen M. A. Smets and Marco Monticone for their cooperation in revising this paper.