Prevalence of Pain and Effect of Joint Strength on Perceived Physical Function in Pediatric Patients With Ehlers–Danlos Syndrome

Abstract

Objective

To identify how pediatric patients with hypermobile-type Ehlers–Danlos syndrome (hEDS) present to physical therapy (PT) and better understand their musculoskeletal dysfunction.

Design

Patients were included in the study if they had a diagnosis of hEDS and at least 1 completed PT evaluation after diagnosis. A chart review was conducted to assess joint strength and pain characteristics at the initial PT assessment. Physical Function Mobility (PF-Mobility; 4 domains with 1-5 scale with higher score representative of better physical function) as part of the Patient-Reported Outcome Measurement Information System and pain intensity score (visual analog scale, 0-10 scale where a lower number indicates less pain) was completed by participants.

Setting

Midwestern tertiary care center.

Participants

Sixty-nine participants were included in the study with an average age of 16.4 years (SD 2.8) at the initial PT visit and 96% were female individuals.

Intervention

Not applicable.

Main Outcome Measures

Joint strength, pain intensity and location, and PF-Mobility.

Results

The knee was the most reported location with pain (68%) followed by the shoulder (46%), hip (41%), and back (39%). Average pain intensity was 5.0 (SD 1.8), joint strength scores ranged from 8.2 (SD 0.9) to 9.9 (SD 0.4), and the PF-Mobility mean was 3.3 (SD 0.6). No correlation was noted between joint pain intensity and strength at the joint.

Conclusions

Although the participants perceived poor mobility and significant pain, PT-assessed strength did not reveal significant muscle weakness. Additional work is needed to explore this discrepancy, including altered biomechanics, evaluation methods, and nonmusculoskeletal factors such as neuropathic and psychological components.

The Ehlers–Danlos syndromes (EDS) represent a group of heritable, collagen-based connective tissue disorders with overlapping phenotypical features.¹ The best estimates indicate an incidence of about 1 in 5000, although this may be an underestimate.² There are 14 subtypes of EDS and 19 different genes that have been identified in the disease process and are primarily involved in collagen and extracellular matrix synthesis and maintenance.³ The EDS subtypes exhibit heterogeneity in clinical features, genetic components, and inheritance patterns. Clinical sequelae for patients with EDS involve many body systems, which include cardiovascular, gastrointestinal, dermatologic, and musculoskeletal issues.⁴ Among the 14 different subtypes of EDS, hypermobile-type Ehlers–Danlos syndrome (hEDS) constitutes 80%-90% of cases but is the only subtype without an identified genetic mutation.⁵ Diagnosis is based on the clinical criteria that include, but not limited to, chronic pain, recurrent joint dislocations, specific skin findings, and family history.⁴ Hypermobile EDS has associations with various other conditions, such as orthostatic hypertension,⁶ mast cell activation disorders, anxiety, and depression.⁷

Many providers are unfamiliar with hEDS caused by the perceived rareness of the condition, whereas many are also uncomfortable with management of EDS caused by the complexity of multiple comorbidities.^8,9 Musculoskeletal sequelae such as joint instability, pain, subluxations, and dislocations are common symptoms for those with hEDS and represent a significant portion of the disease burden. Symptoms may occur spontaneously or with minimal trauma and lead to both acute and chronic pain.¹⁰ Treatment approaches are broad and include compressive bracing, pain medications, injections, physical therapy (PT), psychological intervention, and occasionally surgery for recurrent joint complications.¹¹ PT is considered a first-line recommendation for patients due to muscle weakness, joint disturbances, and musculoskeletal pain.¹² Prior studies show that 30%-55% of patients with hEDS participate in PT, and many have demonstrated pain reduction and strength improvement with consistent PT.⁹ In addition, a systematic review showed patients with shoulder joint hypermobility do have potential benefits from conservative management, which may improve strength and function¹³; however, there is currently no standard approach or set of treatment guidelines for joint hypermobility or hEDS. Typically, the general approach to treatment focuses on a tailored individual approach that focuses on patient needs¹⁴ through a variety of approaches such as braces for joint stability, low-resistance exercises to improve strength, and balance exercises for enhanced proprioception.⁵ Although PT has been beneficial for patients with EDS, there are gaps in knowledge about how pediatric patients primarily present to physical therapists. The characterization of baseline function on referral to physical therapists is an appropriate initial step to improve access to informed care.⁸

The objective of this study was to identify how pediatric patients with hEDS initially present to physical therapists to understand what musculoskeletal dysfunction is present. It was hypothesized that joint strength would be impaired, and this would be associated with greater joint pain and decreased physical function.

Methods

Study design

A convenience sample of adolescents and young adults, aged 10-22 years who were diagnosed with hEDS,⁴ and completed at least 1 PT appointment after diagnosis of hEDS within our institution, were eligible for inclusion in the study. The study took place in a Midwestern tertiary care center between June 2020 and January 2023. Participants completed self-report measures of physical function and pain. A chart review was completed for each participant to assess initial PT evaluation after hEDS diagnosis to identify problematic, painful joints, and joint strength.

Measures evaluated

Joint strength analysis

Joint strength was obtained at up to 12 individual joints per participant. In the evaluation of those joints, a maximum of 38 individual movements were assessed per participant, which includes abduction, adduction, flexion, and extension. Joint strength was graded on a scale of 1− to 5+ using the modified Medical Research Council scale for grading strength.¹⁵ The values were converted to a 10-point scale for analysis using a muscle grading conversion chart, with a higher score indicating greater joint strength.¹⁵ Scores range from the absence of muscle contraction (0) to holding joint position against forceful pressure (10). Joint strength was evaluated in flexion and extension. For the shoulder, abduction was additionally evaluated, and for the hip, abduction and adduction were additionally evaluated.

Physical function mobility (PF-Mobility)

The Patient-Reported Outcome Measurement Information System (PROMIS) Pediatric Profile-25 version 2.0 (PROMIS Pediatric-25 Profile v2.0) was completed. This survey assesses the quality of life and general health outcomes across diseases. It has a set of 6 four-item short forms that measure domains of anxiety, depressive symptoms, fatigue, pain interference and intensity, peer relationships, and PF-Mobility. Patient responses were based on perception of their average pain over the previous 7 days. Each item is rated on a 5-point Likert scale except for pain intensity, which is a 10-point Likert scale, and the PROMIS measures were scored using a straight sum score from the raw values. Higher PROMIS scores represent more of the domain of interest. The physical function domain includes the ability to participate in sports, get up from the floor, navigate stairs, and perform daily activities. Only the PF-Mobility and pain intensity scores are reported in this study.

Joint Pain Locations: As part of physical therapy initial evaluation after hEDS diagnosis, the number of painful joints and specific locations of painful joints were evaluated. Pain was assessed over the previous 7 days as reported by the participant and documented in the medical record.

Statistical analysis

Participant characteristics, the number of painful joint locations, pain intensity, joint strength, and PF-Mobility were reported with averages and standard deviations. Pearson's correlations were conducted to evaluate the relationships between PF-Mobility, pain intensity, and joint strength.

Ethical approval and informed consent

This work was conducted under the Declaration of Helsinki. A local institutional review board (IRB) approval was obtained (IRB Study ID: 16060435), and formal informed consent was not required for this study.

Results

Participant characteristics

Sixty-nine participants were included in the study with an average age of 16.4 years (SD 2.8) at the initial PT visit and 96% were female individuals. The average time between initial diagnosis and initial PT visit was 17 months with 2 participants who had PT evaluation the same day but after their formal diagnosis of hEDS. All participants listed pain as their chief complaint for PT evaluation, and 92% (n=46) of those noted joint hypermobility as part of their reason for presentation to PT. Of the 69 participants, 47 had all study elements completed (PROMIS Pediatric-25 Profile v2.0, joint strength analysis, and joint pain location).

Joint pain locations

The average pain intensity was 5.0 (SD 1.8; table 1). Specific locations were reported in 96% of participants with a total of 8 separate locations, which included knee, shoulder, hip, ankle, back, neck, wrist, and foot (fig 1). The knee was the most reported location with pain identified in 68% of participants followed by the shoulder in 46%, hip in 41%, and back in 39%.

Table 1.

Joint pain and strength average and correlations

Joint Pain and Strength†			Correlations
	Mean	SD	Pain (n=47)	Ankle (n=14)	Knee (n=35)	Shoulder (n=21)	Hip (n=23)
Pain	5.0	1.8	1
Ankle	9.9	0.4	−0.13	1
Knee	9.3	0.9	−0.11	0.10	1
Shoulder	8.6	1.0	−0.29	−0.16	0.62*	1
Hip	8.2	0.9	−0.24	0.06	0.67*	0.78*	1

^⁎P value<.01.

^†A higher score indicates greater pain and strength with a maximum score of 10. Joint strength is an average of available movements assessment averaged across all participants.

Fig 1.

Prevalence of pain by joint location (n=47).

Joint strength and physical function

The knee, shoulder, hip, and ankle were the most evaluated joints, with other joints evaluated less frequently. Joint strength was 9.9 (SD 0.4) in the ankle, 9.3 (SD 0.8) in the knee, 8.6 (SD 1.0) in the shoulder, and 8.2 (SD 0.9) in the hip (table 1). The joint strength represents an average of up to 8 individual movements per joint averaged across all participants. When stratified by each movement for individual joints, joint strength was similar to an intrajoint standpoint except for the hip. The average joint strength for hip flexion was 9.3, extension was 7.6, abduction was 7.8, and adduction was 8.3.

The PROMIS Pediatric-25 Profile v2.0 was completed by 68 participants. The PF-Mobility domain subtotal scores were 2.5 (SD 1.1) for the ability to participate in sports, 3.7 (SD 0.9) to get up from the floor, 3.3 (SD 1.1) to perform daily activities, and 3.6 (SD 1.2) to navigate stairs. The average summative PF-Mobility domain score was 3.3 (SD 0.6) across all participants (table 2).

Table 2.

Physical function mobility scores (PF-mobility)^*

Domain	Mean Score (SD) (n=69)
Participate in sports	2.5 (1.1)
Get up from the floor	3.7 (0.9)
Perform daily activities	3.3 (1.1)
Navigate stairs	3.6 (1.2)
PF-mobility summative score	3.3 (0.6)

^⁎PF-mobility is one domain of the Patient-Reported Outcome Measurement Information System (PROMIS) Pediatric Profile-25 version 2.0. Higher PROMIS scores represent more of the domain of interest with 0-5 scale.

Relationships between joints and pain

Positive correlations were observed between multiple joints and joint strength (hip, knee, and shoulder), and a negative correlation was seen between shoulder and ankle strength (r=−0.16). Joint pain had a weak, negative correlation with joint strength at the ankle (r=−0.13), knee (r=−0.11), shoulder (r=−0.29), and hip (r=−0.24) (table 1).

Discussion

Hypermobile EDS is a chronic disease with heterogeneity in presentation and treatment regimens. We report that most children with hypermobile EDS present to PT with pain in the lower extremities and poor perception of mobility, despite the appropriate muscle strength as assessed by PT. Previous reports suggest that PT should be a mainstay of treatment for patients with hEDS because benefits are gained in strength and pain reduction.⁹ It is important to understand the initial presentation to PT to help tailor early, specific treatment that can improve pain, strength, and health outcomes.

Consistent with other studies,^11,16 pain is the primary complaint noted for children with hEDS who present to PT. This study shows that most children experience knee pain, but almost half also have shoulder, hip, and ankle pain. The previous studies of pain locations for children similarly showed the knee as one of the most common sites seen in more than 50% of individuals.^17,18 This suggests that initial PT should consider evaluation and treatment for the knee and lower extremities but also should be considered more diffusely as many joints can be affected with pain.

In individuals with joint hypermobility, joint strength is often cited as contributing to pain and instability.¹⁹ However, this study showed no correlation between joint strength and pain intensity. In addition, we see that joint strength was not significantly reduced compared to normal strength levels, but musculoskeletal pain is present, and the perception of mobility is poor. This indicates that PT-evaluated strength in this population, assessed by manual isotonic muscle testing, does not correlate with their perceived mobility at the initial presentation. This phenomenon may represent an opportunity to evaluate how joint strength is assessed because there is likely more nuance present for individuals with joint hypermobility, and we may need to focus on other factors that affect movement and physical exertion, such as joint biomechanics, muscle imbalances, compensation, or psychosocial contributions, such as fear of movement (kinesiophobia). Previous studies have shown that some patients with joint hypermobility do not have satisfactory outcomes with PT,¹⁹ and it has been suggested that some patient may need a different type of PT such as high-load strength training as opposed to low-intensity strength training.²⁰ Delving deeper into specific joint dynamics, movement biomechanics, and other associated comorbidities could inform the development of targeted PT protocols tailored specifically for individuals with EDS or joint hypermobility.

The etiology of pain continues to be heavily debated as to whether it predominantly stems from mechanical impairments, nociceptive alterations, psychosocial influences, or a multifaceted interplay.^21,22 A previous report of adults with joint hypermobility showed that most had significant kinesiophobia compared to the general population and this correlated highest with fatigue.²³ It was proposed that pain led to kinesiophobia, which resulted in fatigue and activity adjustment. The kinesiophobia started a cycle that led to an interplay of worsening symptoms.²⁴ Because of this, kinesiophobia should be assessed in children with joint hypermobility to determine whether similar mechanisms seen in adults are also present in children. If kinesophobia is confirmed, this could affect the approach to treatment for children with joint hypermobility through PT and adjunct therapies.

Although prior investigations have demonstrated the efficacy of PT interventions in strength improvements and functionality in joint hypermobility, our findings warrant further investigation to determine the etiology of the incongruence between strength, pain intensity, and perception of mobility with longitudinal tracking. In addition, the assessment of a participant's perception of PT may lead to new knowledge around perception and reality of interventions experienced by children with joint hypermobility. An incongruence between objective and perceived improvement in joint strength and functionality may exist despite the continued perception of poor mobility or increased pain intensity despite the objective improvement in joint and muscle strength. The identification of a perceived benefit or lack thereof from PT may allow providers to engage patients’ expectations and outcomes more appropriately.

Although it has been shown that chronic pain is associated with decreased muscle strength and endurance,²⁵ pain as it relates to strength in individuals with joint hypermobility continues to be complex and multifactorial and more studies are needed to tease apart the complex relationship between structural, anatomical, biomechanical, and psychological contributors. There are likely compensatory mechanical mechanisms that contribute to differences in muscle strength, stability, and mechanical pain that are unique to everyone with joint hypermobility. Further, the current measures of muscle strength in people with joint hypermobility may need to be reevaluated to capture the nuance as it relates to stability, laxity, endurance, and strength. In addition, psychosocial factors should be assessed more granularly with pain evaluation in individuals with joint hypermobility because psychosocial factors are known to affect overall pain and play a role in chronic pain.²⁶

Study limitations

Joint strength was determined by multiple physical therapists, which could introduce bias. However, this study was completed at 1 institution, and the physical therapists used standardized quantitative assessments for values such as range of motion, which makes consistent data more likely. Another limitation is the retrospective nature of the study, which does not provide detail on the causative nature of pain; however, this was not the intention of this study. Other limitations include the conduct of this study at 1 site and the cross-sectional nature of this study that investigated initial presentation to PT and not longitudinal progression after PT, so the results may not be generalizable. In addition, muscle strength was assessed with manual isotonic testing, which is the standard of care; however, more potentially robust methods such as isokinetic or machine measured are available and could provide more granular data and results. Further, PT referrals may have been for a specific problem outside of EDS, so the evaluation may have been more focused rather than generalized; however, the PT providers take a general musculoskeletal history, which provides additional information despite the specific referral concern. Of importance, the nosology for EDS in pediatric patients changed after this study was completed, and the pediatric joint hypermobility framework²⁷ was developed. It is applied to pediatric patients aged 5 years to skeletal maturity or 18 years, and then the 2017 International Diagnostic Criteria for EDS⁴ will be used.

Conclusions

This study evaluated how children with hEDS presented to PT. Participants mostly noted pain in the knees, shoulders, and hips. Although participants reported significant pain intensity and perceived poor mobility, PT-assessed strength was mostly normal. Altered biomechanics, evaluation methods, other nonmusculoskeletal factors, or a combination of factors could explain this difference. Further investigation is warranted to better elucidate the differences identified between patients’ perception and PT assessment, which may help direct and develop treatment protocols for individuals with joint hypermobility.

Disclosures

The authors declare that there are no conflicts of interest.