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Evaluation of Kinesiophobia and Its Correlations with Pain and Fatigue in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type

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Unlabelled: 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 kinesiophobia in disease manifestations, but no study has systematically addressed this point. Objective: To investigate the impact of kinesiophobia and its relationship with pain, fatigue, and quality of life in JHS/EDS-HT. Design: Cross-sectional study. Subjects/patients: 42 patients (40 female and 2 male) with JHS/EDS-HT diagnosis following standardized diagnostic criteria were selected. Methods: Disease features were analyzed by means of specific questionnaires and scales evaluating kinesiophobia, pain, fatigue, and quality of life. The relationships among variables were investigated using the Spearman bivariate analysis. Results: Kinesiophobia resulted predominantly in the patients' sample. The values of kinesiophobia did not correlate with intensity of pain, quality of life, and (or) the single component of fatigue. A strong correlation was discovered between kinesiophobia and general severity of fatigue. Conclusions: In JHS/EDS-HT, the onset of pain-avoiding strategies is related to the presence of pain but not to its intensity. The clear-cut correlation between kinesiophobia and severity of fatigue suggests a direct link between musculoskeletal pain and fatigue. In JHS/EDS-HT, the underlying mechanism is likely to be facilitated by primary disease characteristics, including hypotonia.
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BioMed Research International
Volume , Article ID , pages
http://dx.doi.org/.//
Research Article
Evaluation of Kinesiophobia and Its Correlations with Pain
and Fatigue in Joint Hypermobility Syndrome/Ehlers-Danlos
Syndrome Hypermobility Type
Claudia Celletti,1Marco Castori,2Giuseppe La Torre,3and Filippo Camerota1
1Physical Medicine and Rehabilitation, Department of Orthopaedics, Sapienza University, Umberto I Hospital,
Piazzale Aldo Moro 3, 00185 Rome, Italy
2Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, 00151 Rome, Italy
3Department of Public Health and Infectious Diseases, Sapienza University, Umberto I Hospital, 00185 Rome, Italy
Correspondence should be addressed to Claudia Celletti; c celletti@libero.it
Received  April ; Accepted  June 
Academic Editor: Liam McGun
Copyright ©  Claudia Celletti et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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
kinesiophobia in disease manifestations, but no study has systematically addressed this point. Objective.Toinvestigatethe
impact of kinesiophobia and its relationship with pain, fatigue, and quality of life in JHS/EDS-HT. Design. Cross-sectional study.
Subjects/Patients.  patients ( female and  male) with JHS/EDS-HT diagnosis following standardized diagnostic criteria were
selected. Methods. Disease features were analyzed by means of specic questionnaires and scales evaluating kinesiophobia, pain,
fatigue, and quality of life. e relationships among variables were investigated using the Spearman bivariate analysis. Results.
Kinesiophobia resulted predominantly in the patients’ sample. e values of kinesiophobia did not correlate with intensity of pain,
quality of life, and (or) the single component of fatigue. A strong correlation was discovered between kinesiophobia and general
severity of fatigue. Conclusions. In JHS/EDS-HT, the onset of pain-avoiding strategies is related to the presence of pain but not to
its intensity. e clear-cut correlation between kinesiophobia and severity of fatigue suggests a direct link between musculoskeletal
pain and fatigue. In JHS/EDS-HT, the underlying mechanism is likely to be facilitated by primary disease characteristics, including
hypotonia.
1. Introduction
Ehlers-Danlos syndrome (EDS) is an umbrella term for
various hereditary connective tissue disorders (HCTDs)
mainly characterized by congenital joint hypermobility, skin
hyperextensibility,andtissuefragility.Amongthesixmajor
forms [], the classic and the hypermobility (EDS-HT) types
areconsideredthemostcommon.EDS-HTtypicallyfeatures
joint laxity and related complications, chronic/recurrent limb
pain, and minor skin involvement [], although its extended
clinical spectrum covers a wide variety of functional somatic
syndromes []. An international panel of experts now con-
siders EDS-HT one and the same as joint hypermobility
syndrome (JHS) [], and this overlap is particularly evident
in adulthood. e diagnosis of JHS/EDS-HT still remains
unsupported by molecular testing, with the exception of a
very few cases purportedly mutated in COL3A1 and TNXB
[]. More recently, the relevance of previous molecular
ndings has been further reduced by the separation of
patients mutated in TNXB, who are now grouped under a
distinct EDS subtype (i.e., TNXB-decient EDS) []. At the
moment, recognition of JHS/EDS-HI is uniquely based on
clinical diagnostic criteria [,], which needs urgent revision
[].
Pain and fatigue are considered relevant determinants
of disability in JHS/EDS-HT []. However, their manifes-
tations and pathophysiology remain poorly characterized.
Accumulated data demonstrate that pain is oen chronic
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and widespread in EDS [] and associates positively with
residual joint hypermobility, dislocations, previous surgery,
and low nocturnal sleep quality []. Limb pain, though
considered originating mostly from primary joint damage,
shows some neuropathic features in / patients []. Such
preliminary ndings anticipate a complex pathophysiology
for pain in JHS/EDS-HT, in which cognitive aspects are likely
tostronglyaectqualityoflife.Accordingly,Rombautetal.
[] commonly encountered fear of falling among women
with JHS/EDS-HT.
Chronic musculoskeletal conditions, predominantly
characterized by chronic pain, are oen associated with fear
[]. Fear is the emotional reaction to a specic, identiable,
and immediate threat, such as a dangerous animal or injury
[]. Pain-related fear can be dened as the fear that emerges
when stimuli that are related to pain are perceived as a
main threat []. Fear in relation to pain is described in
three constructs: pain-related fear, fear of movement, and
kinesiophobia []. Kinesiophobia is the most extreme
form of fear of movement, and is dened as an excessive,
irrational and debilitating fear of physical movement and
activity resulting from a feeling of vulnerability to painful
injury or reinjury, and it has been reported as a common
feature of patients with CFS [], bromyalgia, and chronic
low back pain []. Fear-avoidance is said to play a role in
the so-called deconditioning syndrome which can either
be expressed in a weakened muscle strength, or disordered
muscle coordination, during physical activity [].
In this study, we carried out a questionnaire on 
JHS/EDS-HT patients in order to evaluate the presence and
severity of kinesiophobia and to analyze its relationship with
pain, fatigue, and quality of life (QoL). Implications of the
results in the treatment of JHS/EDS-HT are discussed below.
2. Patients and Methods
2.1. Patient Selection. 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 [] and the Villefranche criteria
for EDS-HT []. Patients were included if they met at least
oneofthesetwosets.Inourclinicalpractice,theBrighton
criteria are the most stringent for young-adult, adult, and
elderly patients, while the Villefranche criteria are the best
for individuals in the pediatric age group. For this study,
JHM was mainly assessed applying the Beighton score [].
Further joint or group of joints were equally evaluated
although, at the moment, their status do not inuence
diagnosis establishment. e Beighton score is a -point
evaluation with attribution of one point in the presence of any
ofthefollowingfeatures:(a)passiveappositionofthethumb
to the exor aspect of the forearm (one point for each hand),
(b) passive dorsiexion of the V nger beyond (one point
T : General characteristics.
Characteristic Frequency
(total = ) %
Gender (female/male) / ./.
Positive family history  .
Contortionism in pediatric age  .
Motor delay/clumsiness .
Residual joint hypermobility (Beighton )  .
Recurrent () joint dislocations  .
Recurrent () so tissue lesions  .
Chronic back pain  .
Chronic arthralgias  .
Chronic myalgias  .
Chronic fatigue  .
Recurrent headaches  .
Unrefreshing sleep  .
Impaired memory/concentration  .
Velvety/sm o o t h s k i n   .
Hyperextensible skin  .
Easy bruising  .
Eyelid ptosis  .
Varicose veins/hemorrhoids .
Hernias  .
Uterine/vesical/rectal prolapse .
for each hand), (c) hyperextension of the elbow beyond 10
(one point for each arm), (d) hyperextension of the knee
beyond 10(one point for each leg), and (e) forward exion of
the trunk with the knees extended and the palms resting at
on the oor. Skin/supercial connective tissue features were
assessed qualitatively on the basis of accumulated experience
by palpation and gentle stretching of the skin at the volar
aspect of the palm (at the IV metacarpal) and/or of the
forearm. Other HCTDs were excluded clinically. Patients
were also evaluated to search other secondary symptoms of
the pathology that are showed in Tab l e  .Individualswith
incomplete diagnosis were equally excluded. us, a group
of patients with insucient features of JHS for a rm clinical
diagnosis based on the available diagnostic criteria, but likely
to be liable to develop full-blown JHS, were not included
in this study. Pregnant women and patients older than ,
or younger than , were not included in order to better
homogenize the sample.
2.2. Evaluation Tools. In order to evaluate kinesiophobia,
pain, and fatigue, all patients were asked to ll in a series
of questionnaires including the Tampa Scale Italian version
(TSK-I) [], the Fatigue Severity Scale (FSS) [], the
Multidimensional Fatigue Inventory Scale (MFI-) [], and
the Numeric Rating Scale (NRS-) for pain []. Data were
also compared with quality of life, which was evaluated by the
Medical Outcome Study Short Form- (SF-) [].
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2.2.1. Kinesiophobia. TSK-I is the most widely used question-
naire to assess pain and pain-related fear of movement in
subjects with musculoskeletal complaints [,], and this
hasbeentranslatedintoandvalidatedindierentlanguages
including Italian []. TSK-I is divided into two sub-scales:
evaluating activity avoidance (TSK-AA: a belief that activities
causingpainshouldbeavoided)andharm (TSK-H: a belief
that pain is a sign of bodily damage), respectively. TSK-I is
able to distinguish the fear of movement domain from other
conceptual domains such as pain and functional alteration.
e original version of the TSK-I questionnaire comprises 
items to assess the subjective rating of kinesiophobia [].
Each item has a four-point Likert scale with scoring alter-
natives ranging from “strongly disagree” to “strongly agree.
A total sum is calculated aer inversion of the individual
scores of items , , , and . e total score ranges between
 and . A high TSK-I value indicates a high degree of
kinesiophobia. In the Italian version [],items,,,and
wereexcludedwithatotalscoreofandamaximumscore
for activity avoidance and harm of  and , respectively.
2.2.2. Fatigue. FSS is a scale quantifying fatigue intensity,
which has been used in dierent chronic conditions, such as
multiple sclerosis and systemic lupus erythematosus [], and
shows high internal consistency and validity. FSS comprises
 items with a -point response format that indicates the
degree of agreement with each statement []. MFI- is a -
item self-reporting instrument designed to measure fatigue
[]. It covers the following dimensions: general fatigue (GF),
physical fatigue (PF), mental fatigue (MF), reduced motiva-
tion (RM), and reduced activity (RA). e questionnaire is
constructed with an equal number of questions for each of the
ve suggested dimensions. It has been demonstrated that it is
reliable and valid and has been tested in various conditions,
such as cancer or chronic fatigued patients [].
2.2.3. Pain. NRS is a rapid-to-administrate -point numeric
scale used to roughly measure any kind of pain with a score
ranging from  (no pain) to  (acute pain).
2.2.4. Quality of Life. e Medical Outcome Study -item
Short-Form Health Survey (SF-) is a multipurpose, short
form health survey to evaluate aspects of health most closely
related to quality of life with  questions that measure 
conceptual domains: physical functioning, physical limita-
tion, bodily pain, general health, vitality, social functioning,
emotional limitation, and mental health. e raw scores in
each domain are transformed into  to  scale with higher
scores indicating better quality of life []. e questionnaire
has been translated into Italian and thoroughly validated in
the Italian context [].
2.3. Statistical Analysis. Statistical analysis was conducted
with the SPSS soware package for Windows, version ..
e Kolmogorov-Smirnov probability test was used to assess
thenormalityofthedistributions.eFSSmeanscore
was compared with normal healthy adult scores extracted
from Krupp et al. []usingtheonesamplet-test. SF-
T : Rough data of the Beighton score, TSK-I, MFI-, FSS,
NRS (pain), and FS-.
Variabl e Me an ±SD (range)
Beighton score 5.47 ± 1.97 (–)
TSK-I 34.40 ± 5.85 (–)
TSK-AA 15.52 ± 3.48 (–)
TSK-H 18.88 ± 3.26 (–)
MFI-, GF 17.59 ± 3.12 (–)
MFI-, PF 16.90 ± 2.86 (–)
MFI-, RA 14.33 ± 4.04 (–)
MFI-, RM 12.71 ± 2.54 (–)
MFI-, MF 14.26 ± 4.64 (–)
FSS 5.42 ± 1.77 (–)
NRS (pain) 7.09 ± 1.49 (–)
SF-, PF 45.23 ± 25.42 (–)
SF-, RP 17.26 ± 26.18 (–)
SF-, BP 25.91 ± 21.73 (–)
SF-, GH 26.45 ± 16.30 (–)
SF-, VT 30.11 ± 20.01 (–)
SF-, SF 38.39 ± 25.66 (–)
SF-, RE 43.88 ± 40.43 (–)
SF-, MH 55.52 ± 23.77 (–)
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-): physical functioning;
PF (MFI-): physical fatigue; RA: reduced activity; RE: role-emotional; RM:
reduced motivation; RP: role-physical; SF: social functioning; SF-: short
form ; TSK-AA: Tampa Scale activity avoidance; TSK-H: Tampa Scale
harm; TSK-I: Tampa Scale total score; VT: vitality.
scores were compared with a sample of the normal Italian
population []usingtheonesamplet-test.
e 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-
, the NRS mean scores, and the SF- in all subforms,
while TSK-I, TSK-AA, and TSK-H scores were considered
dependent variables. Subsequently, a separate multivariate
linear regression analysis was performed for TSK-I, TSK-
AA, and TSK-H as dependent variables, using the Backward
elimination stepwise method and including only indepen-
dent variables that show 𝑃 < 0.250 at the univariate analyses.
e signicance level was set at 𝑃 < 0.05.
3. Results
Forty-two patients ( females and  males; mean age at
evaluation: . ±. years) were selected. Clinical char-
acteristics of the patient samples are summarized in Tabl e  .
Table  illustrates numerical values of the following variables
used for further statistical analysis: Beighton score, TSK-I,
FSS, MFI-, NRS (pain), and SF-. In the patient popula-
tion, the mean score of TSK-I and its sub-scales (TSK-AA and
TSK-H) were higher than the value previously xed as the
cut o for establishing the presence of fear of movement [],
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T : Results of the Spearman bivariation analysis comparing TSK-I, TSK-AA, and TSK-H values (as dependent variables) with dierent
variables.
Variable TSK-I TSK-AA TSK-H
Age . (𝑃 = 0.62). (𝑃 = 0.088) . (𝑃 = 0.356)
Beighton score . (𝑃 = 0.67) . (𝑃 = 0.889). (𝑃 = 0.49)
NRS . (𝑃 = 0.93) . (𝑃 = 0.667) . (𝑃 = 0.973)
FSS . (P<0.001) . (P<0.001) . (P=0.01)
MFI-, GF . (P=0.037) . (P=0.02) . (𝑃 = 0.15)
MFI-, PF . (𝑃 = 0.06) . (P=0.03) . (𝑃 = 0.18)
MFI-, RA . (𝑃 = 0.14) . (P=0.01) . (𝑃 = 0.68)
MFI-, RM . (𝑃 = 0.72). (𝑃 = 0.888) . (𝑃 = 0.24)
MFI-, MF . (P=0.004) . (P=0.001) . (𝑃 = 0.11)
SF-, PF . (𝑃 = 0.23). (𝑃 = 0.22). (𝑃 = 0.41)
SF-, RP . (𝑃 = 0.28). (𝑃 = 0.25). (𝑃 = 0.48)
SF-, BP . (𝑃 = 0.51). (𝑃 = 0.66). (𝑃 = 0.49)
SF-, GH . (𝑃 = 0.76). (𝑃 = 0.31) . (𝑃 = 0.58)
SF-, VT . (P=0.03). (𝑃 = 0.06). (𝑃 = 0.08)
SF-, SF . (𝑃 = 0.15). (𝑃 = 0.17). (𝑃 = 0.28)
SF-, RE . (𝑃 = 0.49). (𝑃 = 0.20) . (𝑃 = 0.89)
SF-, MH . (P=0.01). (P=0.02). (𝑃 = 0.05)
Signicant 𝑃values are in bold.
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-): physical functioning; PF (MFI-): physical fatigue; RA: reduced activity; RE: role-emotional; RM: reduced
motivation; RP: role-physical; SF: social func tioning; SF-: short form ; TSK-AA: Tampa Scale activity avoidance; TSK-H: Tampa Scale harm; TSK-I: Tampa
Scale total score; VT: vitality.
T : Multivariate linear regression analysis using the Backward elimination stepwise method.
Variable TSK-I TSK-AA TSK-H
Age . (𝑃 = 0.43). (𝑃 = 0.08) . (𝑃 = 0.499)
Sex . (𝑃 = 0.825) . (𝑃 = 0.592). (𝑃 = 0.789)
FSS . (P<0.01) . (P=0.000) . (P=0.001)
MFI-, GF . (𝑃 = 0.81). (𝑃 = 0.670). (𝑃 = 0.858)
MFI-, PF . (𝑃 = 0.679) . (𝑃 = 0.685) . (𝑃 = 0.90)
MFI-, RA . (𝑃 = 0.819) . (𝑃 = 0.231). (𝑃 = 0.159)
MFI-, MF . (𝑃 = 0.84) . (𝑃 = 0.550). (𝑃 = 0.820)
SF-, MH . (𝑃 = 0.20). (𝑃 = 0.32). (𝑃 = 0.30)
SF-, VT . (𝑃 = 0.89) . (𝑃 = 0.085). (𝑃 = 0.53)
𝑅2of the model . . .
Signicant 𝑃values are in bold.
FSS: fatigue severity scale; GF: general fatigue; MF: mental fatigue; MFI: multimensional fatigue inventory; MH: mental health; PF: physicalfatigue; RA: reduced
activity;SF-:shortform;TSK-AA:TampaScaleactivityavoidance;TSK-H:TampaScaleharm;TSK-I:TampaScaletotalscore;VT:vitality.
with the % of patients with high score values. FSS and FS-
 and all its domains were compared with those previously
registered in the general population [,]. All values
were higher in the patient samples with a signicance of
𝑃 < 0.001. Results of the Spearman bivariation analysis
comparing the TSK-I, TSK-AA, and TSK-H values with
theselectedvariablesaresummarizedinTable .Tabl e 
shows results of the multivariate linear regression analysis
by the Backward elimination stepwise method. e most
consistent association was the one between TSK-I (including
both domains) and FSS (Figure ). Association between TSK-
I and some MFI- domains appeared weaker, though still
statistically signicant in relation to the Spearman bivariation
analysis.
4. Discussion
Pain-related fear is a particular characteristic of patients with
musculoskeletal disorders []andplaysanimportantrolein
explaining disability and in transition from acute to chronic
musculoskeletal pain []. From this perspective, kinesio-
phobia (i.e., cognitive fear of movement or reinjury) can
lead to the stopping/reduction of various activities thought
BioMed Research International
TSK-I
45
40
35
30
25
20
15
1234567
FSS
R2linear = 0.367
(a)
TSK-AA
25
20
15
10
5
1234567
FSS
R2linear = 0.297
(b)
TSK-H
25
20
15
10
5
1234567
FSS
R2linear = 0.253
(c)
F : 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.
to generate pain with progressive limitation of mobility in
some individuals. e consequent disuse and deconditioning
generatefurtherlossofmuscletone,exibility,andaerobic
capacity, which may explain (bearing in mind the population
under consideration) the transition to the third disease
phase in JHS/EDS-HT [,]symptomprogression.In
this phase, psychological and physical disability is marked
with many patients suering from anxiety, depression, and
somatosensory amplication [] and some obliged to use a
wheelchair.
Overall, the present study, conducted through a ques-
tionnaire-based investigation into  patients, in which there
is a preponderance of females described as characteris-
tic in JHS/EDS-HT even if the mechanism underlying is
unknown [], conrmed the hypothesis that kinesiophobia
is a common symptom in JHS/EDS-HT. We also conrmed
global deterioration of the QoL, moderate/severe bodily pain
and marked fatigue in our patient cohort. Since pain and
fatigue have previously been proposed as relevant factors
determining disability in JHS/EDS-HT [], we tried to
compare the severity of kinesiophobia with the QoL, intensity
of pain and fatigue. Although the bivariate analysis identied
a series of possible correlations (Ta b l e  ), further rening by
multivariate linear regression analysis (Ta b l e  )conrmed
correlation with only general severity of fatigue (i.e., FSS).
Lack of correlation with intensity of pain suggests an intrigu-
ing relationship between kinesiophobia and pathophysiology
of chronic pain in JHS/EDS-HT. In fact, one could expect
that the impact of pain-avoiding strategies is directly linked
to the intensity of perceived pain. is does not hold true in
our sample, where the onset of kinesiophobia is inuenced
by the presence of pain, but not by its severity. erefore, in
JHS/EDS-HT, it is plausible that individual coping strategies
are more relevant than the intensity and/or frequency of the
pain stimulus in generating the psychological and physical
disability related to pain-avoiding behaviours.
BioMed Research International
Conversely, kinesiophobia strongly relates with severity
of fatigue, but not its single components in our sample.
Such a result suggests a direct link between adoption of
pain-avoiding strategies and chronic fatigue. Accordingly, it
could be hypothesized that kinesiophobia may contribute to
the progression and, perhaps, onset of fatigue by bodily disuse
secondary to decreased physical eort. erefore, a three-
phase model of pain-kinesiophobia-fatiguecanbeproposed
by which, in predisposed individuals, repeated musculoskele-
tal traumatism exacerbated by joint hypermobility generates
pain-avoiding strategies, which, in turn, cause/aggravate
fatigue. is mechanism, which may be considered acting in
many chronic pain conditions, appears more pronounced in
JHS/EDS-HT, as hypotonia and hypermobility are primary
features of the disease, and the eects of pain-avoiding
strategies are likely to appear more rapidly and to be more
severe. Recent nding that muscle weakness is associated
with fatigue in EDS is in line with this assumption [].
However, this model of pain-kinesiophobia-fatigue cannot
explain the entire spectrum of clinical variability in JHS/EDS-
HT. In fact, by tracing its natural history, the onset of fatigue
could be independent of joint instability complications and
limb pain, at least in some cases []. e reason why,
in our sample, kinesiophobia does not correlate with QoL
remains unexplained. is probably reects that QoL tools,
such as the SF-, measure multidimensional variables that
are not limited to disability only. Consequently, the eects
that kinesiophobia hasonthemaretoosmalltobestatistically
signicant.
is 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, hope-
fully, substituted, at least in terms of prevention, by regular
physical exercise and cognitive therapies. Various studies
have demonstrated that exercise and tness are benecial in
a biomedical sense of maturation, strengthening, and healing
of bones, tendons, and muscle, while deconditioning refers to
a progressive process of worsening physical tness as reduced
muscular activity []. In JHS/EDS-HT, in particular, doing
moderate and continuous physical activity seems to be useful
in order to keep joint hypermobility and muscle tone, and to
reduce pain, fatigue, and fear of movement.
An individualized, modied, and therapeutic programme
involving a multidisciplinary team is recommended to pre-
vent chronic pain and deconditioning and thereby reduce
suering in JHS/EDS-HT patients.
Conflict of Interests
e authors declare that no conict of interests exists con-
cerning this paper and no nancial support or other benets
are correlated to this work.
Acknowledgments
e authors would like to thank Ellen M. A. Smets and Marco
Monticone for their cooperation in revising this paper.
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... Grahame 17 and Celletti 18 and colleagues observed that the physical sequelae experienced by people with EDS is, in part, amplified with psychological distress and behavioral responses, such as kinesiophobia, a fear of physical movement and activity 19 that collectively contribute to poor quality of life (QOL) and further impairments. Specifically, Scheper et al reported that the behavioral response of kinesiophobia has been shown to lead to physical deconditioning, which can exacerbate joint laxity, and a continued cycle of weakness, joint instability, worsening pain, and further deconditioning. ...
... Exercise and rehabilitation for people with EDS have commonly focused on optimizing physical function with improved muscular strength, 21 proprioceptive acuity, 18,22,23 and postural exercises, such as lumbar spinal stabilization and trunk muscle endurance exercises. 24 While acknowledging exercise and rehabilitation as an important part of EDS care, the evolution of the diagnostic criteria and the diagnostic confusion regarding the type of EDS and inclusion of phenotypically similar but variable conditions 9 has led to exercise and rehabilitation studies that include heterogenous populations. ...
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Objectives : To conduct a systematic review examining the effect of exercise and rehabilitation in people with EDS. Data sources : The following databases were systematically searched: Medline, Medline In-Process/ePubs, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and Cumulative Index to Nursing and Allied Health. The final time point captured by the search is November 27, 2020. Study selection : Eligible study designs included case-control, case-series, prospective cohort, retrospective cohort, and intervention studies of structured exercise or rehabilitation interventions. Eligible populations included adults (≥18 years of age) with EDS (all sub-types) and Hypermobility Spectrum Disorders. The search was restricted to articles published in English. Data extraction : Data was extracted by two independent reviewers. Risk of bias (RoB) was assessed using the Physiotherapy Evidence Database (PEDro) scale for randomized control trials (RCTs), and Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) for non-RCTs. Reporting quality of RCTs was assessed using the Consolidated Standards for Reporting of Trials statement with the harms-extension. Reporting was guided by the PRISMA checklist. Data synthesis : The search yielded ten eligible studies including 330 participants. The study designs included five RCTs, one cohort, two single-arm interventions, one retrospective, and one feasibility study. All studies showed some improvement in a physical and/or psychological outcome following the intervention period. One adverse event (non-serious) potentially related to the intervention was reported. Of the five RCTs, two were rated as high quality with low RoB using PEDro, and the majority of non-RCTs were rated as critical RoB by ROBINS-I. Conclusions : The results suggest that exercise and rehabilitation may be beneficial for various physical and psychological outcomes. Adequately powered and rigorous RCTs of exercise and rehabilitation interventions for people with EDS are needed.
... Excluding neurodevelopmental conditions, this makes temporal sense: The presence and consequences of hypermobility in childhood precedes the typically later emergence of psychiatric disorders in adolescence and adulthood. When symptomatic from a young age, the daily challenges of living with physical risks and difficulties associated with HDS/hEDS (including chronic pain and disability, threat of injury secondary to connective tissue fragility, restriction of social and physical activities and associated stigma) contribute to psychiatric vulnerability, avoidant behaviours and the development of anxiety and depressive symptoms [75]. ...
... In addition, problematic hypermobility is typically under-recognised and diagnostic delay is common [3]. Consequently, patients may experience frustration if their complaints are trivialised by healthcare professionals, adding to suffering and exclusion [75]. High anxiety and distress may drive October 19, 2021 ...
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... Three textures were considered: hard, medium hard, and soft depending on the compressibility and springback. The shape of the sponges, square or rectangular, with a width comfortable to be contained by the palm of the physiotherapist's hand, had a variable height from 5 to 10 centimeters [11], the Tampa scale (TSK) [12,13], the fatigue severity scale (FSS) [14], the Oswestry disability index (ODI) [15], and the numerical rating scale (NRS) [16] for pain. ...
... FSS is a scale quantifying fatigue intensity, which has been used in different chronic conditions, such as multiple sclerosis and systemic lupus erythematosus, and shows high internal consistency and validity. FSS comprises 9 items with a 7-point response format that indicates the degree of agreement with each statement [14]. ...
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Background: The hypermobile type of Ehlers-Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue mainly characterized by joint hypermobility. Patients with hEDS suffer joint pain, in particular low back pain, commonly resistant to drug therapy. The aim of this research was to evaluate a neurocognitive rehabilitation approach based not only on the motion and function recovery but also on the pain management. Methods: In this nonrandomized clinical trial, eighteen hEDS patients (4 males and 14 females) with mean age 21 years (range 13-55) were recruited and evaluated before and after three months of rehabilitation treatment. Results: The outcome scores showed significant statistical results after treatment in reducing pain symptoms (numerical rating scale, P = 0.003; McGill (total score), P = 0.03), fatigue (fatigue severity scale, P = 0.03), fear of movement (Tampa scale, P = 0.003), and pain-associated disability (Oswestry disability index, P = 0.03). Conclusion: The clinical results observed in our study seem to confirm the role of a specific neurocognitive rehabilitation program in the chronic pain management in the Ehlers-Danlos syndrome; the rehabilitation treatment should be tailored on patient problems and focused not only in the recovery of movement but also on pain perception.
... Following from these premises, quality of life (QoL) has been found as significantly reduced in EDS subjects compared with controls [17] and the general population [18]. However, there is still a paucity of data regarding mental health issues in EDS, especially in the Italian population [19,20]. We aimed at investigating the psychological distress, the QoL, and the presence of autistic traits in subjects referred through a third level center for the diagnosis and management of EDS in northern Italy. ...
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Background: Ehlers-Danlos syndromes (EDS) have been associated with psychological distress, comorbid psychiatric disorders, and worsening in quality of life (QoL). Among the neurodevelopmental disorders, autism spectrum disorders (ASD) have shown the highest rates of co-occurrence with EDS. The reasons for these associations are unknown and a possible role of pain in increasing the risk of psychiatric disorders in EDS has been suggested. However, a detailed picture of an Italian EDS sample is still lacking. Methods: We conducted a web-based survey in a third level center for the diagnosis of EDS in northern Italy, to investigate psychological distress, QoL, and the presence of autistic traits. Furthermore, we correlated the psychometric data with some clinical variables. Results: We observed a high rate of psychological distress with 91% of the responders at high risk of common mental disorders, low QoL, and high prevalence of autistic traits in EDS patients. Specifically, patients lacking a specific genetic test, diagnosed as suspects of EDS appeared to be at greater risk and reported worse psychological QoL. Pain was significantly associated with both psychological distress and worse QoL. Conclusions: Our findings support the need of further research and of a multi-disciplinary approach to EDS including psychological and psychiatric liaison.
... The biological function of pain is to alter behavior by prioritizing protection and avoidance [121], and it seems likely that pain has a more pronounced effect on physical performance than on its perception [122]. Relative to pain duration, it is possible that individuals with a longer history of chronic pain have implemented dysfunctional coping strategies over the years (such as avoidance of movement and activities due to pain persistence despite treatment) that lead to the development of deconditioning and disuse, thus worsening the actual ability to move [35,123]. ...
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... Kinesiophobia is an exaggerated, irrational fear of movement and activities, caused by the perception of vulnerability as a result of a painful injury or fear of reinjury [23]. This fear can lead chronic pain sufferers to avoid activities and movements that they associate with the occurrence or exacerbation of pain [21,24], resulting in deconditioning and disuse [19,25]. ...
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Individuals suffering from chronic low-back pain and obesity face severe physical and functional limitations. According to the fear-avoidance model, kinesiophobia might play a crucial role in the relationship between pain intensity and disability. Thus, the purpose of this study was to verify the role of kinesiophobia as a mediator in the association between pain intensity and disability in individuals with both chronic low-back pain and obesity. A total of 213 individuals with chronic low-back pain and obesity were included in the study. The level of kinesiophobia, pain intensity and disability were all assessed using self-reported questionnaires. We verified through a simple mediation analysis that kinesiophobia partially mediated the association between pain intensity and disability in our sample. According to our findings, we emphasize the crucial role of kinesiophobia as a psychological factor that should be addressed in chronic low-back pain rehabilitative protocols to reduce disability in individuals with obesity.
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Chronic pain is one of the most common, yet poorly studied, complaints in people suffering from Ehlers–Danlos syndromes (EDS). This heterogeneous group of heritable connective tissue disorders is typically characterized by skin hyperextensibility, joint hypermobility, and generalized connective tissue fragility. Most EDS types are caused by genetic defects that affect connective tissue biosynthesis, thereby compromising collagen biosynthesis or fibrillogenesis and resulting in a disorganized extracellular matrix. Even though chronic pain is a major source of disability, functional impairment, and psychosocial suffering in EDS, currently used analgesics and other treatment strategies provide inadequate pain relief and thus represents an important unmet medical need. An important contributor to this is the lack of knowledge about the underlying mechanisms. In this narrative review, we summarize the current understanding of pain and the associated mechanisms in EDS based on clinical studies focusing on questionnaires and experimental pain testing as well as studies in animal models of EDS. In addition, we highlight the challenges, gaps, and opportunities in EDS-pain research.
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To evaluate progression of symptoms and joint mobility in the joint hypermobility syndrome (JHS) in order to identify specific disease pictures by age at presentation. Fifty JHS patients (44 females, 6 males) were evaluated by Beighton score (BS) calculation, and presence/absence and age at onset of 20 key symptoms. Incidence and prevalence rates by age at onset and sex were calculated and compared by chi-square, Fisher's exact test and Mann-Whitney U-test. Relationship between BS and age at examination was evaluated by the Spearman rho correlation. The existence of an age cut-off separating patients with or without a positive BS was analysed by the receiver operating characteristic analysis. Influence of age on the single components of the BS was also investigated. Except for isolated features, the overall clinical presentation was the same between sexes. In the whole sample, statistically significant differences by age at presentation were registered for fatigue, myalgias, muscle cramps, strains/sprains, dislocations, tendon ruptures, tendonitis, gastroesophageal reflux, chronic gastritis, constipation/diarrhoea and abdominal hernias. A clear inverse correlation between age at examination and BS was demonstrated with an age cut-off fixed at 33 years. Among the components of the BS, spine and elbow joints were not significantly influenced by age. This study confirmed the existence of a protean clinical history of JHS which may be exemplified in different phases with distinguishable presentations. The knowledge of the peculiarities of each of them will help the practitioner in recognising and, hopefully, treating this condition.
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The Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders. The six major, well-defined, subtypes are classified according to diagnostic criteria, formalized in the Villefranche revised nosology. Shortly after the publication of these criteria in 1998, a further distinct type of EDS, the tenascin-X (TNX)-deficient type EDS, was reported. The phenotype of this largely unknown type of EDS resembles the phenotype of the classical type of EDS, but its inheritance is autosomal recessive and wound healing is normal; hence, no atrophic scars are present. The clinical diagnosis can be confirmed by the absence of TNX in the serum and by mutation analysis of the TNXB gene. Because the TNX-deficient type EDS is rare and not included in the current diagnostic criteria, this diagnosis is often delayed or even overlooked. Here, we describe four cases which improve the clinical recognition of this type of EDS.
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Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It has recently been shown that muscle weakness occurs frequently in EDS, and that fatigue is a common and clinically important symptom. The aim of this study was to investigate the relationship between fatigue severity and subjective and objective measures of muscle weakness. Furthermore, the predictive value of muscle weakness for fatigue severity was determined, together with that of pain and physical activity. An explorative, cross-sectional, observational study. Thirty EDS patients, recruited from the Dutch patient association, were investigated at the neuromuscular outpatient department of a tertiary referral centre in The Netherlands. Muscle strength measured with manual muscle strength testing and hand-held dynamometry. Self-reported muscle weakness, pain, physical activity levels and fatigue were assessed with standardised questionnaires. Fatigue severity in EDS was significantly correlated with measured and self-reported muscle weakness (r=-0.408 for manual muscle strength, r=0.461 for hand-held dynamometry and r=0.603 for self-reported muscle weakness). Both muscle weakness and pain severity were significant predictors of fatigue severity in a multiple regression analysis. The results suggest a positive and direct relationship between fatigue severity and muscle weakness in EDS. Future research should focus on the relationship between fatigue, muscle weakness and objectively measured physical activity, preferably in a larger cohort of EDS patients.