Generalized Hyperalgesia in Children and Adults Diagnosed With Hypermobility Syndrome and Ehlers‐Danlos Syndrome Hypermobility Type: A Discriminative Analysis – Scheper – 2017 – Arthritis Care & Research – Wiley Online Library – Pediatric Rheumatology – Free Access – August 2016
The phenotypes of hypermobility syndrome (HMS) and Ehlers‐Danlos syndrome hypermobility type (EDS‐HT) are characterized by generalized connective tissue laxity and connective tissue fragility.
Due to the compromised structural integrity of connective tissue, individuals with HMS/EDS‐HT are assumed to be more prone to injury and consequent disability.
Yes, the above sums up the situation with EDS perfectly.
Box 1. Significance & Innovations
- The current article demonstrates that the presence of generalized hyperalgesia in children with hypermobility syndrome (HMS)/Ehlers‐Danlos syndrome hypermobility type (EDS‐HT) is comparable to adult HMS/EDS‐HT patients. This finding supports the notion that neurologic pathways are involved in the development of chronic musculoskeletal pain, but also indicates that generalized hyperalgesia may not be solely the result of prolonged exposure to pain, as children and adults show similar levels of generalized hyperalgesia. This finding may imply a more fundamental mechanism that is related to HMS/EDS‐HT itself.
- The presence of generalized hyperalgesia was found to be discriminative between healthy controls, subjects with generalized joint hypermobility, and HMS/EDS‐HT subjects. The presence of generalized hyperalgesia may serve as an important diagnostic criterion that may aid in early detection of HMS/EDS‐HT.
The phenotype of HMS/EDS‐HT is not only limited to musculoskeletal involvement but can also involve dysfunction of internal organs, with
- gastrointestinal symptoms,
- disruption of homeostatic regulation such as dysautonomia, and
- altered psychosocial functioning.
The main clinical manifestation identified in the Brighton and Villefranche criteria is the presence of connective tissue laxity, expressed as generalized joint hypermobility (GJH) and hyperelastic skin. Arthralgia in multiple joints for greater than 3 months and recurring joint instability are also included in both diagnostic criteria.
Generalized connective tissue laxity, resulting in joint instability and connective tissue fragility, is assumed to be the origin of chronic, recurrent pain.
Overuse injuries occur with minimal provocation and may lead to reduced activity, to preserve joints.
However, not all individuals with GJH will develop chronic symptoms.
GJH is present in 2–57% of the healthy population, varying with age, sex, and ethnicity.
Researchers estimate that in adults with GJH, 3.3% of women and 0.6% of men report chronic musculoskeletal symptoms. In children, incidence rates of HMS/EDS‐HT between 4.6% to 13% have been documented.
Further complicating the difficulties in diagnosing HMS/EDS‐HT is the lack of understanding of the mechanisms involved in the development of pain and functional decline in this population
While several theories have been proposed for the cause of the onset of musculoskeletal symptoms, ranging from activity‐related biomechanical joint overload to maladaptive pain coping strategies, no single pathway has been identified.
It seems wrong to assume that there must be a “single pathway”:
First of all, biological systems are usually fail-safe and have alternate ways of accomplishing the same tasks.
Secondly, EDS pain comes from multiple sources and cannot simply be generalized: the pinching pain in my knees is very different from the burning back pain between my shoulders or the bone-deep ache in my sacrum.
Although the symptom profile of HMS/EDS‐HT involves multilevel dysfunction, patients report pain as their most frequent symptom.
Arthralgia and muscle pain are reported by 100% and 87% of these patients, respectively, with sites of the highest prevalence being the legs, back, neck, and shoulders
In addition, moderate to severe pain is continuously present, albeit with a variable course of development and persistence. In hypermobile individuals, such as dancers, episodes of pain not persisting into chronicity are highly prevalent and are also associated with disability.
Previous research has shown that pain is an important negative influence with detrimental effects on functional status, social interaction, and psychosocial functioning.
How refreshingly honest compared to the constant accusations of catastrophizing we have to fend off.
Rombaut et al demonstrated that in female EDS‐HT patients, pressure‐pain thresholds were significantly lower in both symptomatic and nonsymptomatic areas.
I would agree; I’ve always considered myself to be unusually pain sensitive.
Within the natural course of HMS/EDS‐HT, a sensitization phase may be present that is responsible for the onset of chronicity and further disability.
The presence of generalized hyperalgesia supports such a mechanism of sensitization, but at what age or in what timeframe generalized hyperalgesia develops in HMS/EDS‐HT is not known.
In theory, prolonged exposure to pain will gradually link maladaptive non‐nociceptive stimuli to a pain response, and thus will increase pain sensitivity
However, whether generalized hyperalgesia manifests in children and whether it is uniquely attributed to HMS/EDS‐HT is unknown, as individuals with GJH are frequently exposed to episodes of pain.
Accordingly, the objectives of this study were to
- determine whether generalized hyperalgesia is present in children with HMS/EDS‐HT,
- explore differences in pressure‐pain thresholds between children and adults with HMS/EDS‐HT, and
- determine the discriminative value of generalized hyperalgesia between individuals with HMS/EDS‐HT, subjects with GJH, and healthy controls.
The observed level of pressure‐pain thresholds in children and adults with HMS/EDS‐HT was comparable to those with chronic musculoskeletal diseases such as fibromyalgia and chronic fatigue syndrome , but considerably lower, indicating higher levels of generalized hyperalgesia, than in comparison to those with osteoarthritis , pelvic, and low‐back pain.
Generalized hyperalgesia is assumed to be the result of central nervous system hypersensitization, in which a centrally mediated reduction of peripheral excitation thresholds occur as a result of chronic pain,
Chronic pain in musculoskeletal disorders has been proposed to be the result of neurologic imprinting, an implicit, learned response that has formed a maladaptive memory‐sustaining pain.
As a result, the central nervous system becomes more sensitive to pain and will produce pain responses even when non‐noxious stimuli are detected.
Furthermore, individuals with chronic musculoskeletal conditions associated with chronic pain demonstrate
- slower sensory processing times,
- incorrect localization,
- decreased accuracy in recognition of tactile stimuli and
- proprioceptive deficits.
These findings are in line with previous research conducted in adults with HMS/EDS‐HT, in which slower sensory processing times and proprioceptive deficits have been reported
Generalized hyperalgesia may be the result of chronic pain itself rather than being a unique trait of HMS/EDS‐HT.
Although generalized hyperalgesia was discriminative between individuals with HMS/EDS‐HT, GJH, and healthy controls, this discrimination does not imply that generalized hyperalgesia is a unique feature of HMS/EDS‐HT.
The presence of generalized hyperalgesia in other chronic pain conditions such as fibromyalgia and chronic fatigue syndrome has been documented, indicating that generalized hyperalgesia is associated with an upregulated central nervous system.
Prolonged exposure to pain induces centrally mediated pain sensitivity that expresses itself in lowered peripheral pain excitation thresholds that may then activate nociception in the absence of actual damage
However, central nervous system hypersensitization was also more severe in children with HMS/EDS‐HT in comparison to adults with osteoarthritis or low‐back pain, who have been exposed to longer and more frequent episodes of pain
The main assumption in the pathophysiologic model of HMS/EDS‐HT is that pain may also be a result of actual tissue damage, due to compromised structural integrity of connective tissue.
A combination of increased vulnerability for injury and hypersensitization of the central nervous system may have more profound consequences for pain sensitization, pain amplification, and neurologic imprinting
However, due to a combination of joint instability and proprioceptive deficits, central nervous system hypersensitization may also be a compensatory mechanism for the lack of proprioception obtained from mechanoreceptors in muscles, tendons, and joint capsules
Although research over the past decade has revealed various aspects of the HMS/EDS‐HT phenotype, the pathophysiologic mechanism remains unclear. Several plausible mechanisms have been suggested, varying from localized biomechanical overload, to multisystemic dysfunction, to maladaptive coping
According to the discriminative analysis conducted here, when generalized hyperalgesia is present, an individual is 6 times more likely to have HMS/EDS‐HT
This result suggests that the symptoms of HMS/EDS‐HT may be triggered by a combination of repetitive musculoskeletal injuries and an upregulated central nervous system.
The link between
- the onset of musculoskeletal symptoms, and
- their development over time
may prove to be important and should be further investigated in longitudinal studies, preferably with more direct measures of central nervous system function
Pressure‐pain threshold measurements are relatively easy to implement with proper training, are noninvasive, and are time and cost effective. Despite recent expert opinion suggesting HMS and EDS‐HT are a single entity, controversy remains within the literature as to whether this is the case.
The comparison performed in this study demonstrated no statistically significant differences in the characteristics of children meeting the Brighton and the Villefranche criteria, adding further weight to the argument that they are indeed 1 condition.