Severity classes in adults with hypermobile Ehlers–Danlos syndrome/hypermobility spectrum disorders: a pilot study of 105 Italian patients

In the paper

“At the optimal cut-off of 12.7, we observed a sensitivity of 0.94 (95% CI 0.85, 0.98), specificity of 0.95 (95% CI 0.84, 0.99), positive predictive value of 0.97 (95% CI 0.89, 1.00), negative predictive value of 0.91 (95% CI 0.78, 0.97) and an overall accuracy of 0.94 (95% CI 0.88, 0.98) (Fig. 4).”

In the paper

“Sixty-nine individuals met the Villefranche criteria (72.4%) and 36 met the Brighton criteria (27.6%).”

In the paper

“Accordingly, the COMPASS-31 total score, BPI current intensity (of pain) and SF-36 physical fatigue were considered the more discriminating markers to predict inclusion in the complex (severe) cluster (Fig. 2).”

In the paper

“Sixty-three (60.0%) patients were classified as complex (i.e.severe) and 42 (40.0%)were classified as simplex (i.e.milder).”

In the paper

“A total of 105 patients were selected and distributed in two distinct severity groups.”

• Also stated in: § Results · plain

  “A total of 105 patients were enrolled in this study.”

In the paper

“PCA analysis was performed on 48 continuous items (after scaling data to unit variance) from the six administrated questionnaires.Three main components accounting for 50% of the total amount of variability were identified.”

In the paper

“More specifically, the worse and better values from the different questionnaires aggregated together in cluster one (complex or severe) and cluster two (simplex or milder), respectively.”

In the paper

“This work identified two distinct classes of adults with hEDS/EDS.”

In the paper

“These two groups were clearly distinguishable by the values of all items of the COMPASS-31, SF-36 and ASRS-V1.1,andmost items of the BPI, MFI-20 and FDQ-9 AUC: area under the curve.”

In the paper

“Conversely, no significant differences were noted for the clinical diagnosis according to the old and new nomenclatures (i.e.no excess of hEDS 2017 and Villefranche criteria in the two clusters) and for age.”

In the paper

“Accordingly, the recent literature exploring the clinical ramifications of hEDS and HSD groups together these conditions in a single phenotype termed hEDS/HSD [69].”

What the sources say

• Not checked yetcites [69]

In the paper

“To minimize subjectivity in choosing a cluster solution, we serially performed hierarchical clustering followed by k-means portion clustering upon the regression-based factors directly derived from PCA as follows.”

In the paper

“The 2017 classification also placed an emphasis on the various JH-related co-morbidities as the most likely determinants of quality of life (QoL) in hEDS/HSD [4].”

What the sources say

• Not checked yetcites [4] Castori, 2017, A framework for the classification of joint hypermobility and related conditions, Am J Med Genet C Semin Med Genet source

In the paper

“Symptomatology and QoL were screened by using a set of validated questionnaires selected to explore a wide array of multisystemic involvement.”

In the paper

“For this reason, a continuous spectrum of phenotypes is proposed ranging from asymptomatic, non-syndromic JH to hEDS and passing through HSD [4].”

What the sources say

• Not checked yetcites [4] Castori, 2017, A framework for the classification of joint hypermobility and related conditions, Am J Med Genet C Semin Med Genet source

In the paper

“In contrast, the new hEDS criteria were conceived to simplistically recognize patients with more convincing structural systemic involvement and/or Mendelian transmission within a wider spectrum of JHrelated phenotypes [10].”

What the sources say

• Not checked yetcites [10] Castori, 2017, Contemporary approach to joint hypermobility and related disorders, Curr Opin Pediatr source

In the paper

“To date, the underlying genetic defect is demonstrable in all EDS variants except hypermobile EDS (hEDS), which lacks a confirmatory laboratory test.Hence the diagnosis of hEDS remains based on physical examination, personal history and formal exclusion of other, partially overlapping disorders [3].”

What the sources say

• Not checked yetcites [3] Tinkle, 2017, Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome type III and Ehlers-Danlos syndrome hypermobility type): clinical description and natural history, Am J Med Genet C Semin Med Genet source

In the paper

“Attention was focussed on joints included in the Beighton score (BS), which is, at the moment, considered the best tool for the assessment of generalized JH [16] (supplementary material, section Methods, available at Rheumatology online).”

What the sources say

• Not checked yetcites [16] Juul-Kristensen, 2017, Measurement properties of clinical assessment methods for classifying generalized joint hypermobility—a systematic review, Am J Med Genet C Semin Med Genet source

In the paper

“Fatigue, cardiovascular dysautonomia and functional gastrointestinal disorders are among the leading features that, although not included in the diagnostic criteria, affect the health status of adults with hEDS/HSD [2022].”

What the sources say

• Not checked yetcites [2022]

In the paper

“An exploratory study on 89 JHS children identified five subphenotypes, namely joint affected, athletic, systemic, soft tissue affected and high BMI [11].”

What the sources say

• Not checked yetcites [11] Pacey, 2015, Joint hypermobility syndrome subclassification in paediatrics: a factor analytic approach, Arch Dis Child source

In the paper

“Heterogeneity in terms of disease expression was put forward years ago by our group, when we approached the natural history of what was previously called JHS/hEDS [23,24].”

What the sources say

• Not checked yetcites [23] Castori, 2010, Natural history and manifestations of the hypermobility type Ehlers-Danlos syndrome: a pilot study on 21 patients, Am J Med Genet A source
• Not checked yetcites [24] Castori, 2013, Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type, Am J Med Genet A source

In the paper

“These categories were recognized by the prevalence of selected items, such as BMI by age and number of painful joints.”

What the sources say

• Not checked yetcites [11] Pacey, 2015, Joint hypermobility syndrome subclassification in paediatrics: a factor analytic approach, Arch Dis Child source

In the paper

“the difference in disease expression between sexes is well known in hEDS/HSD”

What the sources say

• Not checked yetcites [25] Castori, 2010, Ehlers-Danlos syndrome hypermobility type and the excess of affected females: possible mechanisms and perspectives, Am J Med Genet A source

In the paper

“In this work, they found that JHS children with a higher incidence of multisystemic involvement and poor postural control more commonly present a deteriorating trajectory with increased functional impairment [12].”

What the sources say

• Not checked yetcites [12] Scheper, 2017, The natural history of children with joint hypermobility syndrome and Ehlers-Danlos hypermobility type: a longitudinal cohort study, Rheumatology (Oxford) source

In the paper

“The same group also traced the trajectories of functional impairment of a similar cohort of 81 patients in a subsequent 3 year longitudinal study [12].”

What the sources say

• Not checked yetcites [12] Scheper, 2017, The natural history of children with joint hypermobility syndrome and Ehlers-Danlos hypermobility type: a longitudinal cohort study, Rheumatology (Oxford) source

In the paper

“Accordingly, the 2017 classification of EDS and related disorders admits the coexistence of relatively healthy individuals respecting the hEDS criteria and severely affected individuals with a diagnosis of HSD.”

In the paper

“At that time, three possible different phases of disease progression were proposed: hypermobility (first phase), pain (second phase) and stiffness (third phase).”

What the sources say

• Not checked yetcites [23] Castori, 2010, Natural history and manifestations of the hypermobility type Ehlers-Danlos syndrome: a pilot study on 21 patients, Am J Med Genet A source
• Not checked yetcites [24] Castori, 2013, Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type, Am J Med Genet A source

In the paper

“Although the relatively small number of males may have negatively influenced the statistical power of the study”

In the paper

“More recently, cardiovascular autonomic abnormalities have been characterized in JHS/ hEDS with a variety of profiles, including postural orthostatic tachycardia syndrome, orthostatic intolerance and neuromediated hypotension [28,29].”

What the sources say

• Not checked yetcites [28] De Wandele, 2016, Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos syndrome, Rheumatology (Oxford) source
• Not checked yetcites [29] Celletti, 2017, Orthostatic intolerance and postural orthostatic tachycardia syndrome in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: neurovegetative dysregulation or autonomic failure?, Biomed Res Int source

In the paper

“We limited our investigation of the various QoL determinants to pain, fatigue, neurodevelopmental attributes and dysautonomic-related symptoms.”

In the paper

“Manifestations of psychological distress were not specifically included and therefore were limited to selected SF-36 items (e.g.psycho-emotional health).”

In the paper

“We already demonstrated that a positive FDQ-9 score is associated with different features affecting QoL in adults with hEDS/HSD [6].”

What the sources say

• Not checked yetcites [6] Morlino, 2019, Italian validation of the functional difficulties questionnaire (FDQ-9) and its correlation with major determinants of quality of life in adults with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder, Am J Med Genet B Neuropsychiatr Genet source

In the paper

“The number of included subjects might affect the power of the study, whose results remain preliminary and considering the presumed rarity of the investigated phenotype.”

In the paper

“Finally, this study was carried out on Italian patients and therefore we do not know if item values will distribute similarly in other populations.”

In the paper

“In other words, patient stratification by severity does not seem determined by the primary features of hEDS/HSD (e.g.pain), but rather by a presumably coexistent additional pathomechanism.”

In the paper

“Dysautonomia has been evoked as a clinically relevant manifestation of JHS [27].”

What the sources say

• Not checked yetcites [27] Hakim, 2004, Non-musculoskeletal symptoms in joint hypermobility syndrome. Indirect evidence for autonomic dysfunction?, Rheumatology (Oxford) source

In the paper

“Some correlations with selected QoL determinants also emerged, as patients with the high BMI subphenotype experienced more pain while those with the soft tissue affected subphenotype reported more fatigue [11].”

What the sources say

• Not checked yetcites [11] Pacey, 2015, Joint hypermobility syndrome subclassification in paediatrics: a factor analytic approach, Arch Dis Child source

In the paper

“This is somewhat in contrast with the consolidated evidence that pain and fatigue are likely the most relevant determinants of QoL in EDS [26].”

What the sources say

• Not checked yetcites [26] Voermans, 2011, Both pain and fatigue are important possible determinants of disability in patients with the Ehlers-Danlos syndrome hypermobility type, Disabil Rehabil source

In the paper

“This might suggest that the severity of hEDS/HSD is not significantly influenced by the 2017 criteria of hEDS and the aging process.”