EDS Research from PubMed NIH proves Pain

Here I’ve collected several PubMed articles about EDS, especially from Marco Castori, which give proof that EDS is a painful condition. These could be useful for informing doctors of the consequences of having this syndrome.


Chronic pain in patients with the hypermobility type of Ehlers-Danlos syndrome: evidence for generalized hyperalgesia. – PubMed – NCBI– Clin Rheumatol. 2015 Jun;

Chronic widespread pain is highly present in patients with the Ehlers-Danlos syndrome hypermobility type (EDS-HT), but up to now, evidence for generalized hyperalgesia is lacking. The aim of this study is to investigate whether pressure pain thresholds (PPTs) at both symptomatic and asymptomatic body areas differ in EDS-HT patients compared to healthy subjects.

Twenty-three women with EDS-HT and 23 gender- and age-matched healthy controls participated. All subjects marked on Margolis Pain Diagram where they felt pain lasting longer than 24 h in the past 4 weeks. Then, they completed several questionnaires assessing pain cognitions, fatigue, disability, and general health status, in order to take the possible influence of these factors on PPTs into account. Patients also completed a form concerning the type of pain they experienced. Thereupon, a blinded researcher assessed PPTs at 14 body locations on the trunk and extremities. PPTs were compared for the two complete groups. In addition, PPTs of patients and controls who did not report pain in a respective zone were compared.

PPTs of the patients were significantly lower compared to those of the control group, also when pain-free samples per zone were compared. The mean (SD) PPT was 2.9 (1.62) kg/cm(2) in the EDS-HT patients and 5.2 (1.88) kg/cm(2) in the controls (P < 0.001). No confounding factors responsible for the observed differences could be revealed. In half of the patient group, a predominantly neuropathic pain component was likely present.

This study provides evidence for the existence of hyperalgesia even in asymptomatic areas (generalized secondary hyperalgesia). The generalized hyperalgesia may represent the involvement of a sensitized central nervous system, which inquires an adapted pain management for this patient group.

Evaluation of Kinesiophobia and Its Correlations with Pain and Fatigue in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type – Biomed Res Int. 2013   Free Full Text

Claudia Celletti, Marco Castori, Giuseppe La Torre, and Filippo Camerota

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.

Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. – PubMed – NCBI – Am J Med Genet A. 2013 Dec;

Castori M1, Morlino S, Celletti C, Ghibellini G, Bruschini M, Grammatico P, Blundo C, Camerota F.

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping connective tissue disorders characterized by chronic/recurrent pain, joint instability complications, and minor skin changes.

Fatigue and headache are also common, although are not yet considered diagnostic criteria. JHS/EDS-HT is a unexpectedly common condition that remains underdiagnosed by most clinicians and pain specialists.

This results in interventions limited to symptomatic and non-satisfactory treatments, lacking reasonable pathophysiologic rationale.

In this manuscript the fragmented knowledge on pain, fatigue, and headache in JHS/EDS is presented with review of the available published information and a description of the clinical course by symptoms, on the basis of authors’ experience. Pathogenic mechanisms are suggested through comparisons with other functional somatic syndromes (e.g., chronic fatigue syndrome, fibromyalgia, and functional gastrointestinal disorders).

The re-writing of the natural history of JHS/EDS-HT is aimed to raise awareness among clinical geneticists and specialists treating chronic pain conditions about pain and other complications of JHS/EDS-HT.

Symptoms’ clustering by disease stage is proposed to investigate both the molecular causes and the symptoms management of JHS/EDS-HT in future studies

Follow-up of:

Natural history and manifestations of the hypermobility type Ehlers-Danlos syndrome: a pilot study on 21 patients.

Castori M, Camerota F, Celletti C, Danese C, Santilli V, Saraceni VM, Grammatico P.

Am J Med Genet A. 2010 Marn

Joint hypermobility syndrome (a.k.a. Ehlers-Danlos Syndrome, Hypermobility Type): an updated critique. – PubMed – NCBI – G Ital Dermatol Venereol. 2013 Feb

Castori M1.

Joint hypermobility syndrome, alternatively termed Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common, though the least recognized heritable connective tissue disorder

recent evidence indicates a wider spectrum of satellite symptoms/dysfunctions, involving practically all major systems and organs.

Accordingly, clinical research on JHS/EDS-HT is moving from rheumatology and clinical genetics to other disciplines, including neurology, clinical psychology, ophthalmology, cardiology and gynecology/obstetrics

As the skin is one of the most commonly affected and, surely, the easiest to assess body part in heritable connective tissue disorders, it is expected that also the dermatologist should be trained to recognize this condition

In this review, JHS/EDS-HT is presented and discussed in separate sections dedicated to all major aspects of diagnosis, differential diagnosis, clinical features, natural history and principles of management. Particular attention is posed on the role of epidermal, dermal and mucosal assessment in JHS/EDS-HT is order to rise the attention to a series of too neglected, though quite common manifestations of this condition

Management principles are presented with a multidisciplinary approach in mind, covering pharmacologic, physical and occupational therapy, surgical, and nutriceutical aspects, as well as general lifestyle recommendations. Connections with organs and systems other than joints and skin are also discussed

Castori has done much research on EDS. A PubMed search finds 7  pertinent articles

Evaluation of Kinesiophobia and Its Correlations with Pain and Fatigue in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type – Biomed Res Int. 2013 – Free Full-Text PMC article

Claudia Celletti, 1 ,* Marco Castori, 2  Giuseppe La Torre, 3  and Filippo Camerota 1

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.

Spectrum of mucocutaneous manifestations in 277 patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. – PubMed – NCBI – Am J Med Genet C Semin Med Genet. 2015 Mar

Castori M, Dordoni C, Morlino S, Sperduti I, Ritelli M, Valiante M, Chiarelli N, Zanca A, Celletti C, Venturini M, Camerota F, Calzavara-Pinton P, Grammatico P, Colombi M.

Cutaneous manifestations are a diagnostic criterion of Ehlers-Danlos syndrome, hypermobility type (EDS-HT) and joint hypermobility syndrome (JHS). These two conditions, originally considered different disorders, are now accepted as clinically indistinguishable and often segregate as a single-familial trait. EDS-HT and JHS are still exclusion diagnoses not supported by any specific laboratory test. Accuracy of clinical diagnosis is, therefore, crucial for appropriate patients’ classification and management, but it is actually hampered by the low consistency of many applied criteria including the cutaneous one.

We report on mucocutaneous findings in 277 patients with JHS/EDS-HT with both sexes and various ages. Sixteen objective and five anamnestic items were selected and ascertained in two specialized outpatient clinics. Feature rates were compared by sex and age by a series of statistical tools. Data were also used for a multivariate correspondence analysis with the attempt to identify non-causal associations of features depicting recognizable phenotypic clusters.

Our findings identified a few differences between sexes and thus indicated an attenuated sexual dimorphism for mucocutaneous features in JHS/EDS-HT. Ten features showed significantly distinct rates at different ages and this evidence corroborated the concept of an evolving phenotype in JHS/EDS-HT also affecting the skin. Multivariate correspondence analysis identified three relatively discrete phenotypic profiles, which may represent the cutaneous counterparts of the three disease phases previously proposed for JHS/EDS-HT.

These findings could be used for revising the cutaneous criterion in a future consensus for the clinical diagnosis of JHS/EDS-HT.

Heart rate, conduction and ultrasound abnormalities in adults with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. – PubMed – NCBI |2014 Jul

Camerota F1, Castori M, Celletti C, Colotto M, Amato S, Colella A, Curione M, Danese C.

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue disorders strongly associating with pain, fatigue and other secondary aspects.

Though not considered a diagnostic criterion for most EDS subtypes, cardiovascular involvement is a well-known complication in EDS.

A case-control study was carried out on 28 adults with JHS/EDS-HT diagnosed according to current criteria, compared to 29 healthy subjects evaluating resting electrocardiographic (ECG), 24-h ECG and resting heart ultrasound data.

Results obtained in the ECG studies showed a moderate excess in duration of the PR interval and P wave, an excess of heart conduction and rate abnormalities and an increased rate of mitral and tricuspid valve insufficiency often complicating with “true” mitral valve prolapse in the ecocardiographic study. These variable ECG subclinical anomalies reported in our sample may represent the resting surrogate of such a subnormal cardiovascular response to postural changes that are known to be present in patients with JHS/EDS-HT.

Our findings indicate the usefulness of a full cardiologic evaluation of adults with JHS/EDS-HT for the correct management.

Entrapment neuropathies and polyneuropathies in joint hypermobility syndrome/Ehlers-Danlos syndrome. – PubMed – NCBI – Aug 2013

Clin Neurophysiol. 2013 Aug;

Granata G1, Padua L, Celletti C, Castori M, Saraceni VM, Camerota F

OBJECTIVE:

This study aims to investigate the involvement of the peripheral nervous system in Ehlers-Danlos syndromes/hypermobility type patients with particular attention to entrapment syndromes.

METHODS:

We consecutively enrolled Ehlers-Danlos syndromes/hypermobility type patients. Patients underwent clinical, neurophysiological and ultrasound evaluations. Dynamic ultrasound evaluation was also performed in healthy subjects as control group.

RESULTS:

Fifteen Ehlers-Danlos syndromes/hypermobility type patients and fifteen healthy subjects were enrolled. Most of patients presented tingling, numbness, cramps in their hands or feet. Clinical evaluation was normal in all patients. One patient was affected with carpal tunnel syndrome and one with ulnar nerve entrapment at elbow. One patient had an increased and hypoechoic ulnar nerve at elbow at ultrasound evaluation. Dynamic ultrasound evaluation of ulnar nerve at elbow showed, in patients, twelve subluxations and three luxations. In the control group dynamic evaluation showed one case of ulnar nerve luxation.

CONCLUSION:

Statistical analysis showed a significant difference in the occurrence of ulnar nerve subluxation and luxation between patients and control subjects.

SIGNIFICANCE:

The study shows an inconsistency between symptoms and neurophysiological and ultrasound evidences of focal or diffuse nerve involvement. The high prevalence of ulnar nerve subluxation/luxation at elbow in Ehlers-Danlos syndromes/hypermobility type patients could be explained by the presence of Osborne ligament laxity.

Nosology and inheritance pattern(s) of joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type: a study of intrafamilial and in… – PubMed – NCBI – Am J Med Genet A. 2014 Dec;

Nosology and inheritance pattern(s) of joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type: a study of intrafamilial and interfamilial variability in 23 Italian pedigrees.

Castori M1, Dordoni C, Valiante M, Sperduti I, Ritelli M, Morlino S, Chiarelli N, Celletti C, Venturini M, Camerota F, Calzavara-Pinton P, Grammatico P, Colombi M

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two markedly overlapping heritable connective tissue disorders. The cumulative frequency of JHS and EDS-HT seems high, but their recognition remains an exclusion diagnosis based on different sets of diagnostic criteria.

Although proposed by a panel of experts, clinical identity between JHS and EDS-HT is still a matter of debate due to unknown molecular basis.

We present 23 families with three or more individuals with a diagnosis of JHS and/or EDS-HT. Rough data from the 82 individuals were used to assess the frequency of major and minor criteria, as well as selected additional features. A series of statistical tools were applied to assess intrafamilial and interfamilial variability, emphasizing intergenerational, and intersex differences.

This study demonstrates marked heterogeneity within and between families in terms of agreement of available diagnostic criteria. In 21 pedigrees affected individuals belong to two or three phenotypic sub-categories among JHS, EDS-HT, and JHS + EDS-HT overlap. Intergenerational analysis depicts a progressive shifting, also within the same pedigree, from EDS-HT in childhood, to JHS + EDS-HT in early adulthood and JHS later in life. Female-male ratio is 2.1:1, which results lower than previously observed in unselected patients’ cohorts. In these pedigrees, JHS, EDS-HT, and JHS + EDS-HT segregate as a single dominant trait with complete penetrance, variable expressivity, and a markedly evolving phenotype.

This study represents a formal demonstration that EDS-HT and JHS constitute the same clinical entity, and likely share the same genetic background, at least, in familial cases.

Symptom and joint mobility progression in the joint hypermobility syndrome (Ehlers-Danlos syndrome, hypermobility type). – PubMed – NCBI – Clin Exp Rheumatol. 2011 Nov-Dec

Castori M1, Sperduti I, Celletti C, Camerota F, Grammatico P

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

A study of migraine characteristics in joint hypermobility syndrome a.k.a. Ehlers-Danlos syndrome, hypermobility type. – PubMed – NCBI – Neurol Sci. 2015 Mar

A study of migraine characteristics in joint hypermobility syndrome a.k.a. Ehlers-Danlos syndrome, hypermobility type.

Puledda F1, Viganò A, Celletti C, Petolicchio B, Toscano M, Vicenzini E, Castori M, Laudani G, Valente D, Camerota F, Di Piero V.

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue disorders strongly associated with musculoskeletal pain, fatigue and headache. Migraine with or without aura is considered the most common form of headache in JHS/EDS-HT. In this population of chronically ill patients, we investigated whether migraine characteristics were different from those of a control population of migraine patients.

The study was carried out on 33 selected JHS/EDS-HT patients, diagnosed according to current criteria. Sixty-six migraine subjects matching age and gender were consecutively selected as controls (MO group) among patients attending our Headache Clinic. JHS/EDS-HT and MO were screened for a series of headache characteristics, such as frequency, intensity, age of onset, level of disability, use of rescue and prophylactic medications. Differences between the two groups were tested by using independent group comparisons.

Results showed that in JHS/EDS-HT: (1) migraine has an earlier onset (12.6 vs 17 years of age; p = 0.005); (2) the rate of migraine days/month is higher (15 vs 9.3 days/month; p = 0.01); (3) accompanying symptoms are usually more frequent; (4) HIT-6 and MIDAS scores are higher (p = 0.04 and p = 0.03); (5) efficacy of rescue medication is almost identical, although, total drug consumption is significantly lower (p < 0.04).

Joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type patients have a more severe headache syndrome with respect to the MO group, therefore demonstrating that migraine has a very high impact on quality of life in this disease

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3 thoughts on “EDS Research from PubMed NIH proves Pain

  1. Ladygrateful

    You are amazing and even though I know you don’t get the kuddos you deserve I want you to know that what you do is so important and even if I cant get the doctors by me to listen to anything at least I know the truth I live it and you provide scientific proof so that I don’t feel crazy. I have two of my three kids with different variations of EDS so I see it from a personal and parental level. I was a productive citizen working full-time starting at 15 until last February at 41 when I was no longer able. I was the main financial support. I worked for 20 years in education and when you get sick there is no state disability none. So I have been unable to work and with no income for a year and a half. Life is a beautiful crazy mess but I am grateful to people like you who in the face of immense adversity are able to provide this invaluable information to those of us unable to do so. Anyhow I know this is all over the place but I am grateful for all you are and all you do. So thank you :)

    Liked by 1 person

    Reply
    1. Zyp Czyk Post author

      I’m honored and delighted by your sincere praise. It truly warms my heart and fuels my enthusiasm to keep at it.

      Hearing that it’s helpful to people like you is the reason I do this work!

      Like

      Reply

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