Update on joint hypermobility - Aug 2018

Review 

Cattalini M, Khubchandani R, Cimaz R. When flexibility is not necessarily a virtue: a review of hypermobility syndromes and chronic or recurrent musculoskeletal pain in children. Pediatr Rheumatol Online J. 2015 Oct 6;13(1):40. doi: 10.1186/s12969-015-0039-3. PubMed PMID: 26444669; PubMed Central PMCID: PMC4596461. Full text 

Chronic or recurrent musculoskeletal pain is a common complaint in children. Among the most common causes for this problem are different conditions associated with hypermobility. Pediatricians and allied professionals should be well aware of the characteristics of the different syndromes associated with hypermobility and facilitate early recognition and appropriate management. In this review we provide information on Benign Joint Hypermobility Syndrome, Ehlers-Danlos Syndrome, Marfan Syndrome, Loeys-Dietz syndrome and Stickler syndrome, and discuss their characteristics and clinical management.

Function and injury risks

Sohrbeck-Nøhr O, Kristensen JH, Boyle E, Remvig L, Juul-Kristensen B. Generalized joint hypermobility in childhood is a possible risk for the development of joint pain in adolescence: a cohort study. BMC Pediatr. 2014 Dec 10;14:302. doi: 10.1186/s12887-014-0302-7. PubMed PMID: 25492414; PubMed Central PMCID: PMC4305244.

BACKGROUND:  There is some evidence that indicates generalized joint hypermobility (GJH) is a risk factor for pain persistence and recurrence in adolescence. However, how early pain develops and whether GJH without pain in childhood is a risk factor for pain development in adolescence is undetermined. The aims for this study were to investigate the association between GJH and development of joint pain and to investigate the current GJH status and physical function in Danish adolescents.

METHODS:  This was a longitudinal cohort study nested within the Copenhagen Hypermobility Cohort. All children (n = 301) were examined for the exposure, GJH, using the Beighton test at baseline at either 8 or 10 years of age and then re-examined when they reached 14 years of age. The children were categorized into two groups based on their number of positive Beighton tests using different cut points (i.e. GJH4 defined as either < 4 or ≥ 4, GJH5 and GJH6 were similarly defined). The outcome of joint pain was defined as arthralgia as measured by the Brighton criteria from the clinical examination. Other outcome measures of self-reported physical function and objective physical function were also collected.

RESULTS: Children with GJH had three times higher risk of developing joint pain in adolescence, although this association did not reach statistical significance (GJH5: 3.00, 95% [0.94-9.60]). At age 14, the adolescents with GJH had significantly lower self-reported physical function (for ADL: GJH4 p = 0.002, GJH5 p = 0.012; for pain during sitting: GJH4 p = 0.002, GJH5 p = 0.018) and had significantly higher body mass index (BMI: GJH5 p = 0.004, GJH6 p = 0.006) than adolescents without GJH. There was no difference in measured physical function.

CONCLUSION: This study has suggested a possible link between GJH and joint pain in the adolescent population. GJH was both a predictive and a contributing factor for future pain. Additional studies with larger sample sizes are needed to confirm our findings.


Junge T, Larsen LR, Juul-Kristensen B, Wedderkopp N. The extent and risk of knee injuries in children aged 9-14 with Generalised Joint Hypermobility and knee joint hypermobility - the CHAMPS-study Denmark. BMC Musculoskelet Disord. 2015 Jun 12;16:143. doi: 10.1186/s12891-015-0611-5. PubMed PMID: 26065679; PubMed Central PMCID: PMC4465013.

BACKGROUND: Generalised Joint Hypermobility (GJH) is suggested as an aetiological factor for knee injuries in adolescents and adults. It is presumed that GJH causes decreased joint stability, thereby increasing the risk of knee injuries during challenging situations like jumping and landing. The aim was to study the extent and risk of knee injuries in children with GJH and knee hypermobility.

METHODS: In total, 999 children (9-14 years) were tested twice during spring 2012 and 2013 with Beighton's Tests (BT) for hypermobility, a 0-9 scoring system. GJH was classified with cut-point ≥5/9 on both test rounds. On basis of weekly cell phone surveys of knee pain, children requiring clinical examination were seen. Traumatic and overuse knee injuries were registered by WHO ICD-10 diagnoses. Logistic regression and Poisson regression models with robust standard errors were used to examine the association between GJH and knee injuries, taking into account clustering on school class levels.

RESULTS: Totally, 36 children were classified GJH on both test rounds. Overuse knee injuries were the most frequent injury type (86 %), mainly apophysitis for both groups (61 %), other than patella-femoral pain syndrome for the control group (13 %). For traumatic knee injuries, distortions and contusions were most frequent in both groups (51 % resp. 36 %), besides traumatic lesions of knee tendons and muscles for the control group (5 %). No significant association was found between overuse knee injuries and GJH with/without knee hypermobility (OR 0.69, p = 0.407 resp. OR 0.75, p = 0.576) or traumatic knee injuries and GJH with/without knee hypermobility (OR 1.56, p = 0.495 resp. OR 2.22, p = 0.231).

CONCLUSIONS: Apophysitis, distortions and contusions were the most frequent knee injuries. Despite the relatively large study, the number of children with GJH and knee injuries was low, with no significant increased risk for knee injuries for this group. This questions whether GJH is a clinically relevant risk factor for knee injuries in school children aged 9-14 years. A fluctuation in the individual child's status of GJH between test rounds was observed, suggesting that inter- and intra-tester reproducibility of BT as well as growth may be considered important confounders to future studies of children with GJH.


Physiotherapy and joint hypermobility

Palmer S, Cramp F, Clark E, Lewis R, Brookes S, Hollingworth W, Welton N, Thom H, Terry R, Rimes KA, Horwood J. The feasibility of a randomised controlled trial of physiotherapy for adults with joint hypermobility syndrome. Health Technol Assess. 2016 Jun;20(47):1-264. doi: 10.3310/hta20470. PubMed PMID: 27365226; PubMed Central PMCID: PMC4947876.

BACKGROUND: Joint hypermobility syndrome (JHS) is a heritable disorder associated with laxity and pain in multiple joints. Physiotherapy is the mainstay of treatment, but there is little research investigating its clinical effectiveness.

OBJECTIVES: To develop a comprehensive physiotherapy intervention for adults with JHS; to pilot the intervention; and to conduct a pilot randomised controlled trial (RCT) to determine the feasibility of conducting a future definitive RCT.

DESIGN: Patients' and health professionals' perspectives on physiotherapy for JHS were explored in focus groups (stage 1). A working group of patient research partners, clinicians and researchers used this information to develop the physiotherapy intervention. This was piloted and refined on the basis of patients' and physiotherapists' feedback (stage 2). A parallel two-arm pilot RCT compared 'advice' with 'advice and physiotherapy' (stage 3). Random allocation was via an automated randomisation service, devised specifically for the study. Owing to the nature of the interventions, it was not possible to blind clinicians or patients to treatment allocation.

SETTING: Stage 1 - focus groups were conducted in four UK locations. Stages 2 and 3 - piloting of the intervention and the pilot RCT were conducted in two UK secondary care NHS trusts.

PARTICIPANTS: Stage 1 - patient focus group participants (n = 25, three men) were aged > 18 years, had a JHS diagnosis and had received physiotherapy within the preceding 12 months. The health professional focus group participants (n = 16, three men; 14 physiotherapists, two podiatrists) had experience of managing JHS. Stage 2 - patient participants (n = 8) were aged > 18 years, had a JHS diagnosis and no other musculoskeletal conditions causing pain. Stage 3 - patient participants for the pilot RCT (n = 29) were as for stage 2 but the lower age limit was 16 years.

INTERVENTION: For the pilot RCT (stage 3) the advice intervention was a one-off session, supplemented by advice booklets. All participants could ask questions specific to their circumstances and receive tailored advice. Participants were randomly allocated to 'advice' (no further advice or physiotherapy) or 'advice and physiotherapy' (an additional six 30-minute sessions over 4 months). The physiotherapy intervention was supported by a patient handbook and was delivered on a one-to-one patient-therapist basis. It aimed to increase patients' physical activity through developing knowledge, understanding and skills to better manage their condition.

MAIN OUTCOME MEASURES: Data from patient and health professional focus groups formed the main outcome from stage 1. Patient and physiotherapist interview data also formed a major component of stages 2 and 3. The primary outcome in stage 3 related to the feasibility of a future definitive RCT [number of referrals, recruitment and retention rates, and an estimate of the value of information (VOI) of a future RCT]. Secondary outcomes included clinical measures (physical function, pain, global status, self-reported joint count, quality of life, exercise self-efficacy and adverse events) and resource use (to estimate cost-effectiveness). Outcomes were recorded at baseline, 4 months and 7 months.

RESULTS: Stage 1 - JHS is complex and unpredictable. Physiotherapists should take a long-term holistic approach rather than treating acutely painful joints in isolation. Stage 2 - a user-informed physiotherapy intervention was developed and evaluated positively. Stage 3 - recruitment to the pilot RCT was challenging, primarily because of a perceived lack of equipoise between advice and physiotherapy. The qualitative evaluation provided very clear guidance to inform a future RCT, including enhancement of the advice intervention. Some patients reported that the advice intervention was useful and the physiotherapy intervention was again evaluated very positively. The rate of return of questionnaires was low in the advice group but reasonable in the physiotherapy group. The physiotherapy intervention showed evidence of promise in terms of primary and secondary clinical outcomes. The advice arm experienced more adverse events. The VOI analysis indicated the potential for high value from a future RCT. Such a trial should form the basis of future research efforts.

CONCLUSION: A future definitive RCT of physiotherapy for JHS seems feasible, although the advice intervention should be made more robust to address perceived equipoise and subsequent attrition.


Ballet and joint hypermobility

Steinberg N, Hershkovitz I, Zeev A, Rothschild B, Siev-Ner I. Joint Hypermobility and Joint Range of Motion in Young Dancers. J Clin Rheumatol. 2016 Jun;22(4):171-8. doi: 10.1097/RHU.0000000000000420. PubMed PMID: 27219302.

BACKGROUND: Joint range of motion (ROM) refers to the extent of movement of the joint, recorded using standard goniometers. Jointhypermobility (JHM) is a condition in which most of the synovial joints move beyond the "normal" limits. Joint hypermobility is recognized as a feature of heritable disorders of the connective tissue and can be identified mostly by the Beighton scale. Data on the possible relationship between JHM and joint ROM are lacking in the literature. The main objective of the present study was to evaluate the relationship between JHM and joint ROM in the different lower-extremity joints in young dancers.

METHODS: Joint hypermobility and ROM were assessed among 240 female dancers, aged 8 to 16 years, and 226 nondancers of similar age.

RESULTS: The prevalence of JHM is significantly higher among dancers compared with the control subjects (P < 0.001). Joints' ROM is higher among dancers with JHM compared with dancers without JHM (P < 0.05). This phenomenon, however, is age dependent; as in young dancers (aged 8-10 years), this pertains only to the ankle dorsiflexion ROM. In adolescent dancers (aged 11-13 years), this relationship has been observed in most joints: ankle/foot en pointe, ankle dorsiflexion, hip external rotation, hip abduction, and hip extension. In mature dancers (aged 14-16 years), dancers with JHM had greater ROM in ankle/foot en pointe, hip abduction, and knee flexion (P < 0.05).

CONCLUSIONS: (1) Joint ROM and JHM are associated one with the other; (2) the relationship between joint ROM and JHM is age dependent; and (3) JHM is common among young nonprofessional dancers compared with control subjects. The main clinical implications of the current study are to try and reduce the risk of injuries among JHM dancers by developing proprioceptive trainings to improve the correct alignment of the hyperextended joints, to increase their muscle strength for better stabilization of the hypermobile joints, and to provide them additional balancing and stabilizing exercises for their supporting muscles.


Quanbeck AE, Russell JA, Handley SC, Quanbeck DS. Kinematic analysis of hip and knee rotation and other contributors to ballet turnout. J Sports Sci. 2016 Mar 25:1-8. [Epub ahead of print] PubMed PMID: 27015006.  http://www.ncbi.nlm.nih.gov/pubmed/27015006

Turnout, or external rotation (ER) of the lower extremities, is essential in ballet. The purpose of this study was to utilise physical examination and a biomechanical method for obtaining functional kinematic data using hip and knee joint centres to identify the relative turnout contributions from hip rotation, femoral anteversion, knee rotation, tibial torsion, and other sources. Ten female dancers received a lower extremity alignment assessment, including passive hip rotation, femoral anteversion, tibial torsion, weightbearing foot alignment, and Beighton hypermobility score. Next, turnout was assessed using plantar pressure plots and three-dimensional motion analysis; participants performed turnout to ballet first position on both a plantar pressure mat and friction-reducing discs. A retro-reflective functional marker motion capture system mapped the lower extremities and hip and knee joint centres. Mean total turnout was 129±15.7° via plantar pressure plots and 135±17.8° via kinematics. Bilateral hip ER during turnout was 49±10.2° (36% of total turnout). Bilateral knee ER during turnout was 41±5.9° (32% of total turnout). Hip ER contribution to total turnout measured kinematically was less than expected compared to other studies, where hip ER was determined without functional kinematic data. Knee ER contributed substantially more turnout than expected or previously reported. This analysis method allows precise assessment of turnout contributors.


Swimming and joint hypermobility

Junge T, Henriksen P, Andersen HL, Byskov LD, Knudsen HK, Juul-Kristensen B. The association between generalized joint hypermobility and active horizontal shoulder abduction in 10-15 year old competitive swimmers. BMC Sports Sci Med Rehabil. 2016 Jul 12;8:19. doi: 10.1186/s13102-016-0044-y. eCollection 2016. PubMed PMID: 27413535; PubMed Central PMCID: PMC4942936. 

BACKGROUND: Increased shoulder mobility and Generalised Joint Hypermobility (GJH) are assumed to be predisposing risk factors for shoulder injuries. The association between GJH and shoulder mobility among competitive swimmers is unknown. The aim was to study the association between GJH and active horizontal shoulder abduction (AHSA) in young, competitive swimmers and to describe normative values of AHSA in this group.

METHODS: In total, 92 swimmers (10-15 years) without shoulder pain participated. GJH was evaluated with the Beighton Tests (BT) for jointhypermobility. Shoulder mobility was measured as maximum AHSA. A multiple regression model was used to assess associations between GJH and AHSA.

RESULTS: Overall, positive associations were found between GJH and AHSA. An increase of BT score was associated with an increase of AHSA, seen as an increased AHSA of 3.9°, 5.7° and 7.9° by BT cut off points ≥5/9, ≥6/9 and ≥7/9, respectively. Normative values for AHSA ranged from 40° to 52°, depending on age.

CONCLUSIONS: Positive associations were found between GJH and AHSA, as maximum AHSA range increased with increasing BT scores. Due to lack of shoulder mobility tests in the BT scoring system, the AHSA test seems to be a promising supplemental test.


Young musicians and GJH

Vinci S, Smith A, Ranelli S. Selected Physical Characteristics and Playing-Related Musculoskeletal Problems in Adolescent String Instrumentalists. Med Probl Perform Art. 2015 Sep;30(3):143-51. PubMed PMID: 26395615.

PURPOSE: Music research has investigated the prevalence of playing-related musculoskeletal problems in adults and children, but the prevalence in adolescents has not been established. String instrumentalists report high problem rates, though it is unclear whether rates vary between upper and lower strings in adolescent instrumentalists. Further, there is limited evidence for the association between physical characteristics and playing problems in this group of musicians.

METHODS: Seventy-six adolescent string musicians from the West Australian Youth Orchestras were surveyed. Their experience of playing problems, both symptoms (PRMS) and disorders (PRMD), within the last month and measurements of body mass index, hand span, and jointmobility (Beighton scale) were obtained. Prevalence rates were calculated and compared between upper and lower string instrumentalists using a chi-squared test. Logistic regression examined the association of physical measures with playing problems, adjusting for confounding factors.

RESULTS: Within the last month, 73.5% participants reported experiencing a PRMS and 26.5percnt; reported experiencing a PRMD. There was no significant difference between the problem rates in upper and lower string instrumentalists. After adjusting for potential confounders, an increasing count of hypermobile joints remained significantly associated with problems (OR 1.76, CI 1.02 to 3.04, p=0.042).

CONCLUSIONS:This study found playing problems are common in adolescent string instrumentalists, though rates did not differ between upper and lower string players. Joint hypermobility was associated with playing-related problems in adolescent musicians. Early identification of problems in this group of maturing musicians may help prevent disabling disorders and maximize performance.


Pain, fatigue and anxiety in JHS

Mallorquí-Bagué N, Bulbena A, Pailhez G, Garfinkel SN, Critchley HD. Mind-Body Interactions in Anxiety and Somatic Symptoms. Harv Rev Psychiatry. 2016 Jan-Feb;24(1):53-60. doi: 10.1097/HRP.0000000000000085. PubMed PMID: 26713718.

Anxiety and somatic symptoms have a high prevalence in the general population. A mechanistic understanding of how different factors contribute to the development and maintenance of these symptoms, which are highly associated with anxiety disorders, is crucial to optimize treatments. In this article, we review recent literature on this topic and present a redefined model of mind-body interaction in anxiety and somatic symptoms, with an emphasis on both bottom-up and top-down processes. Consideration is given to the role played in this interaction by predisposing physiological and psychological traits (e.g., interoception, anxiety sensitivity, and trait anxiety) and to the levels at which mindfulness approaches may exert a therapeutic benefit. The proposed model of mind-body interaction in anxiety and somatic symptoms is appraised in the context ofjoint hypermobility syndrome, a constitutional variant associated with autonomic abnormalities and vulnerability to anxiety disorders.


Kashikar-Zuck S, King C, Ting TV, Arnold LM. Juvenile Fibromyalgia: Different from the Adult Chronic Pain Syndrome? Curr Rheumatol Rep. 2016 Apr;18(4):19. doi: 10.1007/s11926-016-0569-9. Review. PubMed PMID: 26984803.

While a majority of research has focused on adult fibromyalgia (FM), recent evidence has provided insights into the presence and impact of FM in children and adolescents. Commonly referred as juvenile fibromyalgia (JFM), youths, particularly adolescent girls, present with persistent widespread pain and cardinal symptoms observed in adult FM. A majority of youth with JFM continue to experience symptoms into adulthood, which highlights the importance of early recognition and intervention. Some differences are observed between adult and juvenile-onset FM syndrome with regard to comorbidities (e.g., joint hypermobility is common in JFM). Psychological comorbidities are common but less severe in JFM. Compared to adult FM, approved pharmacological treatments for JFM are lacking, but non-pharmacologic approaches (e.g., cognitive-behavioral therapy and exercise) show promise. A number of conceptual issues still remain including (1) directly comparing similarities and differences in symptoms and (2) identifying shared and unique mechanisms underlying FM in adults and youths.


De Wandele I, Rombaut L, De Backer T, Peersman W, Da Silva H, De Mits S, De Paepe A, Calders P, Malfait F. Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos Syndrome. Rheumatology (Oxford). 2016 Aug;55(8):1412-20. doi: 10.1093/rheumatology/kew032. Epub 2016 Apr 18. PubMed PMID: 27094596.

OBJECTIVE: To investigate whether orthostatic intolerance (OI) is a significant predictor for fatigue in Ehlers-Danlos Syndrome, hypermobilitytype (EDS-HT).

METHODS: Eighty patients with EDS-HT and 52 controls participated in the first part of the study, which consisted of questionnaires. Fatigue was evaluated using the Checklist Individual Strength (CIS). As possible fatigue determinants OI [Autonomic Symptom Profile (ASP)], habitual physical activity (Baecke), affective distress [Hospital Anxiety and Depression Scale (HADS)], pain (SF36), medication use and generalizedhypermobility (5-point score of Grahame and Hakim regarding generalized joint hypermobility) were studied. Next, a 20 min head-up tilt (70°) was performed in a subsample of 39 patients and 35 controls, while beat-to-beat heart rate and blood pressure were monitored (Holter, Finometer Pro). Before and after tilt, fatigue severity was assessed using a numeric rating scale.

RESULTS: Patients scored significantly higher on the CIS [total score: EDS: 98.2 (18.63) vs controls: 45.8 (16.62), P < 0.001] and on the OI domain of the ASP [EDS: 22.78 (7.16) vs controls: 6.5 (7.78)]. OI was prevalent in EDS-HT (EDS: 74.4%, controls: 34.3%, P = 0.001), and frequently expressed as postural orthostatic tachycardia (41.0% of the EDS group). Patients responded to tilt with a higher heart rate and lower total peripheral resistance (p < 0.001; p = 0.032). This altered response correlated with fatigue in daily life (CIS). In the EDS-HT group, tilt provoked significantly more fatigue [numeric rating scale increase: EDS: +3.1 (1.90), controls: +0.5 (1.24), P < 0.001]. Furthermore, the factors OI, pain, affective distress, decreased physical activity and sedative use explained 47.7% of the variance in fatigue severity.

CONCLUSION: OI is an important determinant of fatigue in EDS-HT.

Bladder, bowel and autonomic function 

Tokhmafshan F, Brophy PD, Gbadegesin RA, Gupta IR. Vesicoureteral reflux and the extracellular matrix connection. Pediatr Nephrol. 2016 May 2. [Epub ahead of print] Review. PubMed PMID: 27139901.

Primary vesicoureteral reflux (VUR) is a common pediatric condition due to a developmental defect in the ureterovesical junction. The prevalence of VUR among individuals with connective tissue disorders, as well as the importance of the ureter and bladder wall musculature for the anti-reflux mechanism, suggest that defects in the extracellular matrix (ECM) within the ureterovesical junction may result in VUR. This review will discuss the function of the smooth muscle and its supporting ECM microenvironment with respect to VUR, and explore the association of VUR with mutations in ECM-related genes.