Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome
Open accessAbstract
Objective To review the association between orthostatic intolerance syndromes and both joint hypermobility and Ehlers-Danlos syndrome, and to propose reasons for identifying hereditary connective tissue disorders in those with orthostatic intolerance in the context of both clinical care and research. Methods We searched the published peer-reviewed medical literature for papers reporting an association between joint hypermobility or Ehlers-Danlos syndrome and orthostatic intolerance. Results We identified 10 relevant papers. Although methodological variability between studies introduces some limitations, the published literature consistently identifies a significantly higher prevalence of orthostatic intolerance symptoms in patients with joint hypermobility or Ehlers-Danlos syndrome than in healthy controls, and a significantly higher prevalence of cardiovascular and autonomic abnormalities both at rest and during orthostatic challenge. Postural tachycardia syndrome is the most commonly recognized circulatory disorder. The severity of orthostatic symptoms in those with EDS correlates with impairments in quality of life. Conclusion There is a strong association between several forms of cardiovascular dysfunction, most notably postural tachycardia syndrome, and joint hypermobility or Ehlers-Danlos syndrome. We propose that recognition of joint hypermobility and Ehlers-Danlos syndrome among those with orthostatic intolerance syndromes has the potential to improve clinical care and the validity of research findings.
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- Findingnone given§ 4.1. Literature summary · p. 5
Hemodynamic abnormalities are identified in 56-80% of JH/EDS patients in published studies.
“Hemodynamic abnormalities are identi fi ed in 56 -80% of JH/EDS patients in published studies”
Quote in the paperNot a substantial claim - Findingreasoning§ A B S T R A C T · p. 1
The published literature consistently shows a significantly higher prevalence of cardiovascular and autonomic abnormalities both at rest and during orthostatic challenge in patients with joint hypermobility or EDS than in healthy controls.
“a signi fi cantly higher prevalence of cardiovascular and autonomic abnormalities both at rest and during orthostatic challenge”
Quote in the paperSubstantial claim - Findingnone given§ 4.1. Literature summary · p. 5
Higher prevalence rates of hemodynamic abnormalities are reported when orthostatic testing duration exceeds 20 minutes.
“with higher prevalence rates being reported when the orthostatic testing duration exceeds 20 min.”
Quote in the paperNot a substantial claim - Findingown data§ A B S T R A C T · p. 1
The published literature consistently shows a significantly higher prevalence of orthostatic intolerance symptoms in patients with joint hypermobility or EDS than in healthy controls.
“the published literature consistently identi fi es a signi fi cantly higher prevalence of orthostatic intolerance symptoms in patients with joint hypermobility or Ehlers-Danlos syndrome than in healthy controls”
Quote in the paperSubstantial claim - Findingnone given§ A B S T R A C T · p. 1
There is a strong association between several forms of cardiovascular dysfunction, most notably POTS, and joint hypermobility or EDS.
“There is a strong association between several forms of cardiovascular dysfunction, most notably postural tachycardia syndrome, and joint hypermobility or Ehlers-Danlos syndrome.”
Quote in the paperSubstantial claim
- Findingreasoning§ 4.1. Literature summary · p. 5
Between 41 and 100% of patients with JH/EDS report orthostatic symptoms on a regular basis.
“Between 41 and 100% with JH/EDS report orthostatic symptoms on a regular basis”
Quote in the paperNot a substantial claim - Findingnone given§ 4.1. Literature summary · p. 5
Higher prevalence rates of orthostatic symptoms are reported in studies using more comprehensive ascertainment methods.
“with higher prevalence rates being reported in studies using more comprehensive ascertainment methods for those symptoms.”
Quote in the paperNot a substantial claim - Findingnone given§ A B S T R A C T · p. 1
POTS is the most commonly recognized circulatory disorder in patients with joint hypermobility or EDS.
“Postural tachycardia syndrome is the most commonly recognized circulatory disorder.”
Quote in the paperNot a substantial claim - Findingnone given§ A B S T R A C T · p. 1
The severity of orthostatic symptoms in those with EDS correlates with impairments in quality of life.
“The severity of orthostatic symptoms in those with EDS correlates with impairments in quality of life.”
Quote in the paperNot a substantial claim - Interpretationreasoning§ 4.1. Literature summary · p. 5
The available evidence is consistent with higher sympathetic tone in JH/EDS.
“The available evidence is consistent with higher sympathetic tone in JH/EDS”
Quote in the paperNot a substantial claim - Premisecitation§ 5.2.1. To accurately describe the clinical features of study populations · p. 7
In a retrospective review of children with chronic functional pain disorders (11 with joint hypermobility syndrome, 10 without), there were no differences in migraines or other comorbid disorders including orthostatic intolerance.
“In a retrospective review of pediatric patients with chronic functional pain disorders, 11 with JHS and 10 without, there were no di ff erences in migraines or other co-morbid disorders including orthostatic intolerance.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Chelimsky et al., 2016 source
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- Interpretationreasoning§ 5.2.1. To accurately describe the clinical features of study populations · p. 7
If a new POTS study did not screen for joint hypermobility/EDS, chance overrepresentation of those conditions would overestimate the prevalence of beta-receptor hypersensitivity in POTS.
“If a new study did not ascertain for JH/EDS among the POTS population, then a chance recruitment of a study population that overrepresented JH/EDS would lead to an overestimate of the prevalence of beta-receptor hypersensitivity among those with POTS.”
Quote in the paperSubstantial claim - Interpretationreasoning§ 5.1.4. To provide a unifying diagnosis for patients · p. 7
Recognising joint hypermobility or hypermobile EDS in patients with POTS and orthostatic intolerance can help unify the diagnosis of their other chronic symptoms.
“Identifying joint hypermobility or hEDS in those with POTS and orthostatic intolerance can help to provide a unifying diagnosis for the other chronic symptoms.”
Quote in the paperSubstantial claim - Interpretationreasoning§ 5.2.1. To accurately describe the clinical features of study populations · p. 7
Studies of health-related quality of life in POTS risk misrepresenting patients' true quality of life unless the separate effects of joint hypermobility or EDS are measured.
“Studies of health related quality of life (HRQOL) in individuals with POTS risk misrepresenting the true quality of life of a ff ected patients unless the independent e ff ects of joint hypermobility or EDS are measured.”
Quote in the paperSubstantial claim - Premisecitation§ 5.1.1. To improve general clinical management · p. 6
In pregnancy, surgery and vascular procedures, patients with hypermobile EDS face greater risks of delayed wound healing and wound dehiscence.
“during pregnancy, surgery, and vascular procedures, hEDS patients have a higher risk of delayed wound healing and a higher risk of wound dehiscence”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Tinkle et al., 2017 source
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- Interpretationreasoning§ 5.1.3. To ensure provision of appropriate physical therapy care · p. 6
Advancing high impact exercise too rigidly, straining hypermobile joints, may harm patients with hypermobile EDS.
“Rigid advancement of high impact exercise that places excessive strain on hypermobile joints has the potential to cause harm in those with hEDS.”
Quote in the paperSubstantial claim - Interpretationreasoning§ 5.1.1. To improve general clinical management · p. 6
Orthostatic headaches caused by spinal fluid leaks and intracranial hypotension need completely different treatment from those caused by POTS alone.
“Orthostatic headaches due to spinal fl uid leaks and intracranial hypotension would require entirely different management than orthostatic headaches due to POTS alone.”
Quote in the paperSubstantial claim - Premisecitation§ 5.1.1. To improve general clinical management · p. 6
Recognising joint hypermobility and EDS changes general management because of connective tissue laxity and fragility and because of comorbid conditions.
“Recognition of JH and EDS a ff ects general management due to connective tissue laxity and fragility itself, and to the presence of co-morbid conditions (reviewed by Tinkle et al., 2017).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Tinkle et al., 2017 source
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- Premisecitation§ 5.1.1. To improve general clinical management · p. 6
Orthostatic headaches occur commonly in POTS and other orthostatic intolerance syndromes.
“Orthostatic headaches are common in POTS and other forms of orthostatic intolerance (Mack et al., 2010).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Mack et al., 2010 source
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- Interpretationreasoning§ 4.1. Literature summary · p. 5
The available evidence is consistent with a strong association between decreased overall quality of life and the degree of autonomic dysregulation.
“and with a strong association between decreased overall quality of life and the degree of autonomic dysregulation.”
Quote in the paperNot a substantial claim - Premisecitation§ 5.2.1. To accurately describe the clinical features of study populations · p. 7
Older evidence shows that isoproterenol can trigger panic and anxiety in experimental settings.
“older evidence that isoproterenol can provoke panic and anxiety in experimental settings (Rainey et al., 1984; Balon et al., 1990; Pohl et al., 1988; Pohl et al., 1990).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation§ 5.1.2. To detect rare forms of EDS and other hereditary connective tissue disorders · p. 6
Patients with vascular EDS are less likely to have autonomic symptoms than those with classical or hypermobile EDS.
“Although those with vascular EDS are less likely than cEDS and hEDS to have autonomic symptoms (De Wandele et al., 2014a)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites De Wandele et al., 2014a
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- Premisecitation§ 5.2.4. To prevent incorrect causal inferences · p. 7
87% of patients with systemic joint hypermobility and localized condylar hypermobility also had temporomandibular disorders, versus 30% of controls.
“Kavuncu and colleagues found that 87% of patients with systemic joint hypermobility (SJH) and localized condylar hypermobility (LCH) also su ff er from TMD, compared to only 30% of controls (Kavuncu et al., 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kavuncu et al., 2005 source
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- Interpretationreasoning§ 5.2.3. To reduce enrollment of potential non-responders in treatment studies · p. 7
Screening for joint hypermobility and EDS could improve how responses to study interventions are interpreted.
“Screening for joint hypermobility and EDS has the potential to improve the interpretation of responses to study interventions.”
Quote in the paperSubstantial claim - Premisecitation§ 5.1.3. To ensure provision of appropriate physical therapy care · p. 6
Avoiding complete inactivity in POTS is important because complete bed rest can reduce blood volume.
“The avoidance of complete inactivity is important in POTS to prevent reductions in blood volume that can accompany complete bed rest (Takenaka et al., 2002).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Takenaka et al., 2002 source
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- Interpretationreasoning§ 5.2.1. To accurately describe the clinical features of study populations · p. 7
Separating POTS with joint hypermobility/hypermobile EDS from POTS without it would help avoid unbalanced subgroup assignment in pathophysiology studies.
“Distinguishing POTS plus JH/hEDS versus POTS without JH/hEDS would help prevent unbalanced assignment to subgroups in pathophysiology studies.”
Quote in the paperNot a substantial claim - Premisecitation§ 5.1.1. To improve general clinical management · p. 6
Intubation may be difficult in hypermobile EDS because of temporomandibular joint laxity, spinal ligamentous laxity and early intervertebral disc degeneration.
“Intubation can be problematic for hEDS patients due to temporomandibular joint laxity or spinal ligamentous laxity and early intervertebral disc degeneration (Henderson et al., 2017).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Henderson et al., 2017 source
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- Interpretationreasoning§ 5.2.3. To reduce enrollment of potential non-responders in treatment studies · p. 7
A coincidental flare of any of these conditions when a study drug is started could raise background symptom noise and hide the signal of an effective treatment.
“A coincidental exacerbation of any of these conditions at the time a study medication was introduced could increase the background noise of general symptoms, potentially obscuring the signal from an e ff ective intervention.”
Quote in the paperSubstantial claim - Interpretationreasoning§ 5.2.4. To prevent incorrect causal inferences · p. 7
Screening for joint hypermobility and hypermobile EDS in POTS patients could reduce the risk of drawing incorrect causal inferences.
“Screening for joint hypermobility and hEDS in POTS patients has the potential to reduce the risk of drawing incorrect causal inferences.”
Quote in the paperSubstantial claim - Premisecitation§ 5.2.1. To accurately describe the clinical features of study populations · p. 7
Gazit and colleagues reported increased sensitivity to isoproterenol in people with joint hypermobility.
“The data from Gazit and colleagues describe an increased sensitivity to isoproterenol among those with JH.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Gazit et al., 2003 source
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- Interpretationnone given§ 6. Conclusion · p. 7
Joint hypermobility and Ehlers-Danlos syndrome are strongly associated with several forms of orthostatic intolerance, most notably postural tachycardia syndrome.
“There is a strong association between joint hypermobility and Ehlers-Danlos syndrome and several forms of orthostatic intolerance, most strikingly postural tachycardia syndrome.”
Quote in the paperNot a substantial claim - Premisecitation§ 5.1.2. To detect rare forms of EDS and other hereditary connective tissue disorders · p. 6
Diagnosing vascular EDS matters because it carries a higher risk of arterial aneurysms and rupture of hollow organs.
“it would be important to diagnose vEDS because of the increased risk of arterial aneurysms and hollow organ rupture (Byers et al., 2017).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Byers et al., 2017 source
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- Premisecitation§ 5.2.1. To accurately describe the clinical features of study populations · p. 7
73% of patients with POTS and hypermobile EDS had migraines, compared with 28% of those with isolated POTS (P = 0.001).
“Kanjwal and colleagues found that 73% of patients with POTS and hEDS had migraines, compared to 28% of patients with isolated POTS (P = 0.001).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kanjwal et al., 2010
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- May combine two claims. 13
- Classified as probably not a substantial claim. 7
- The quote only partly states this claim. 1
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Findingreasoning§ 4.1. Literature summary · p. 5In all studies with more than 10 patients, the data are consistent with clinically important and statistically significant increases in the prevalence of orthostatic symptoms and objective hemodynamic abnormalities in those with joint hypermobility or EDS, with the highest prevalence among those with hEDS.
“Nonetheless, in all studies with > 10 patients, the data are consistent with clinically important and statistically signi fi cant increases in the prevalence of orthostatic symptoms and objective hemodynamic abnormalities in those with joint hypermobility or EDS, with the highest prevalence being found among those with hEDS.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown data§ A B S T R A C T · p. 1The review's literature search identified 10 relevant papers on the association between orthostatic intolerance or circulatory dysfunction and joint hypermobility or Ehlers-Danlos syndrome.
“We identi fi ed 10 relevant papers.”
- Also stated in: § 4. Association of orthostatic intolerance and circulatory dysfunction with JH/EDS · p. 3 · plain
“The literature review identi fi ed 10 studies that addressed the association between various forms of circulatory dysfunction and JH or EDS.”
Quote in the paperNot a substantial claim- Also stated in: § 4. Association of orthostatic intolerance and circulatory dysfunction with JH/EDS · p. 3 · plain
Probably not a substantial claim: may not pass S4 (based).
Findingnone given§ 4.1. Literature summary · p. 4All published studies have enrolled patients who were being evaluated in academic medical centers or specialty clinics.
“All published studies have enrolled patients who were being evaluated in academic medical centers or specialty clinics.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ 5.2.1. To accurately describe the clinical features of study populations · p. 7In a systematic review of 1006 people with joint hypermobility syndrome and 2951 controls, joint hypermobility was associated with higher odds of anxiety (OR 4.4) and panic disorder (OR 6.7).
“In a large systematic review of 1006 with joint hypermobility syndrome and 2951 controls, those with joint hypermobility had higher odds of anxiety (OR =4.4) and panic disorder (OR = 6.7).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Smith et al., 2014 source
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Premisecitation§ 5.2.3. To reduce enrollment of potential non-responders in treatment studies · p. 7People with hypermobile EDS are at higher risk of many comorbid problems, including gastrointestinal motility disorders, scoliosis, varicose veins, Chiari malformation, craniocervical instability and painful joint dislocation.
“individuals with hEDS have a higher risk of a wide variety of co-morbid problems, including gastrointestinal motility disorders, scoliosis, varicose veins, Chiari malformation, craniocervical instability, painful joint dislocation, and others (Castori, 2012a; Zarate et al., 2010; Milhorat et al., 2007; Henderson et al., 2017).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
Interpretationreasoning§ 5.2.4. To prevent incorrect causal inferences · p. 7POTS confounds the relationship between joint hypermobility/hypermobile EDS and temporomandibular disorders, and the causal pathway runs from connective tissue laxity to both POTS and temporomandibular disorders rather than from dysautonomia to both.
“we would suggest that POTS is a confounder for the relationship between joint hypermobility/hEDS and TMD, and that the true causal pathway leads from connective tissue laxity to both POTS and TMD, rather than from a dysautonomic state to both POTS”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Premisecitation§ 5.2.4. To prevent incorrect causal inferences · p. 7Durham and colleagues found that 17 of 36 adults with POTS (47%) had temporomandibular disorders.
“They identi fi ed 17 (47%) as having TMD and concluded that this elevated prevalence ' adds further support to the conditions having a similar underlying dysautonomic pathophysiology. '”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Durham et al., 2015 source
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Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.
Interpretationreasoning§ 5.2.1. To accurately describe the clinical features of study populations · p. 7Screening for joint hypermobility and hypermobile EDS can improve how study populations are described and let readers judge how representative the findings are.
“Screening for JH and hEDS can improve the description of study populations and thereby allow readers to draw more accurate inferences about the representativeness of study fi ndings.”
Quote in the paperNot a substantial claimMay combine two claims. The quote only partly states this claim.
Interpretationnone given§ 6. Conclusion · p. 7Some patients with hypermobile EDS experience frequent orthostatic symptoms that are linked to reduced quality of life.
“A proportion with hEDS report frequent orthostatic symptoms that correlate with impairments”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitation§ 5.2.4. To prevent incorrect causal inferences · p. 7Other studies suggest joint hypermobility probably precedes and predisposes to both temporomandibular disorders and POTS.
“Other studies, however, suggest that joint hypermobility likely precedes and predisposes to both TMD (De Coster et al., 2005; Kavuncu et al., 2005; Deodato et al., 2006; Pasinato et al., 2011) and POTS (Rowe et al., 1999).”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S2 (checkable), S4 (based). May combine two claims.
Interpretationnone given§ M. Roma et al. · p. 8Paying more attention to how common joint hypermobility and EDS are among people with orthostatic intolerance could improve clinical care and make research results more valid.
“Increased attention to the prevalence of joint hypermobility and EDS in those with orthostatic intolerance syndromes has the potential to improve clinical care and to enhance the validity of research results.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Premisecitation§ 5.1.3. To ensure provision of appropriate physical therapy care · p. 6Training protocols for patients with joint hypermobility must be adapted because of tissue fragility.
“However, in patients with joint hypermobility, training protocols need to be adapted for tissue fragility (Engelbert et al., 2017).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Engelbert et al., 2017 source
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Premisecitation§ 5.2.1. To accurately describe the clinical features of study populations · p. 7No patient with joint hypermobility had a viral infection as a POTS precipitant, versus 15% of the POTS-only group, a difference that was not statistically significant.
“None of the JH patients had experienced a viral infection as a precipitant of POTS, compared to 15% of the POTS only group, but this di ff erence did not reach statistical signi fi cance.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kanjwal et al., 2010
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Premisecitation§ 5.2.1. To accurately describe the clinical features of study populations · p. 7The mean SF-36 physical function score was 55 in POTS and the median in hypermobile EDS was 35; bodily pain scores were 60 in POTS and 35 in hypermobile EDS.
“The mean physical function subscale score was 55 in POTS and the median value in hEDS was 35, with lower scores indicating worse QOL.”
- Also stated in: § 5.2.1. To accurately describe the clinical features of study populations · p. 7 · hedged
“The bodily pain subscale scores also appear to di ff er substantially, 60 in POTS and 35 in hEDS.”
Quote in the paperSubstantial claim0 of 2 sources checked- Also stated in: § 5.2.1. To accurately describe the clinical features of study populations · p. 7 · hedged
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Premisecitation§ 5.1.1. To improve general clinical management · p. 6People with EDS are at higher risk of spontaneous cerebrospinal fluid leaks, which can worsen headaches when upright.
“Individuals with EDS have an increased risk of spontaneous cerebrospinal fl uid leaks, which in turn can contribute to worsening of headaches in positions of upright posture (Mokri et al., 2002).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Mokri et al., 2002 source
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Premisecitation§ 5.2.1. To accurately describe the clinical features of study populations · p. 7Patients with both joint hypermobility and POTS presented at a significantly younger age and had more comorbid syncope (62% vs 30%) than those with isolated POTS.
“Those with JH and POTS presented at a signi fi cantly younger age than those with isolated POTS and had a higher prevalence of co-morbid syncope (62 vs. 30%).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kanjwal et al., 2010
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Interpretationreasoning§ 4.1. Literature summary · p. 4It is unclear how much referral bias influences the findings.
“It is therefore unclear how much referral bias in fl uences the fi ndings.”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitation§ 5.2.4. To prevent incorrect causal inferences · p. 7The odds ratios for hypermobility syndromes in temporomandibular disorders were 11.2 for systemic joint hypermobility, 7.5 for localized condylar hypermobility and 15.3 for both, and the risk was significantly higher when both were present (P < 0.001).
“The odds ratio for hypermobility syndromes in TMD were 11.2 for SJH, 7.5 for LCH and 15.3 for both.”
- Also stated in: § 5.2.4. To prevent incorrect causal inferences · p. 7 · boosted
“This study showed that the risk of TMD was signi fi cantly higher if both LCH and SJH were present (P < 0.001).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kavuncu et al., 2005 source
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- Also stated in: § 5.2.4. To prevent incorrect causal inferences · p. 7 · boosted
The paper relies on this without support.
EDS commonly involves chronic fatigue, and fatigue is a central symptom of several orthostatic intolerance syndromes.
“EDS has long been recognized to be associated with a high prevalence of chronic fatigue, which in turn is a cardinal feature of various forms of orthostatic intolerance.”
The paper relies on this without support.
Diagnosing joint hypermobility or EDS in patients with orthostatic intolerance matters to patients, clinicians, and researchers.
“We discuss the importance to patients, clinicians, and researchers of making the diagnosis of joint hypermobility or EDS in patients who have orthostatic intolerance.”
The paper relies on this without support.
The mechanism behind the higher prevalence of orthostatic intolerance in joint hypermobility and EDS is not well established.
“The mechanism for the increased prevalence of orthostatic intolerance in joint hypermobility and EDS is not well established.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A review of studies found that orthostatic intolerance and tachycardia occurred in 35%-50% of patients with hypermobility spectrum disorder.
“A review of studies that analyzed rates of POTS and other forms of orthostatic intolerance in patients with Ehlers–Danlos syndrome found that orthostatic intolerence and tachycardia occured in 35%–50% of patients with hypermobility spectrum disorder.24”
From Diagnosis and management of postural orthostatic tachycardia syndrome (2022) · cites this paper as [24]
The review reports postural tachycardia in 41% of patients with hypermobile EDS in one study and POTS in 49% of a joint hypermobility syndrome/hypermobile EDS group in another (section 4, p. 4). But it reports orthostatic intolerance at higher rates—74% and 80%, respectively—and does not establish a 35%–50% rate for both conditions in patients specifically diagnosed with hypermobility spectrum disorder. (LLM, conf=0.88)
Experimental — accuracy not yet measuredOrthostatic intolerance is significantly more prevalent in individuals with joint hypermobility or hEDS and is often linked to postural tachycardia syndrome.
“Orthostatic intolerance is significantly more prevalent in individuals with joint hypermobility or hEDS and is often linked to postural tachycardia syndrome [PoTS; (31)].”
From Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain (2022) · cites this paper as [31]
Approximately 40% of POTS patients experience migraine, 20-30% meet criteria for hypermobile Ehlers-Danlos syndrome, and about 15% carry a diagnosis of co-morbid autoimmune disease.
“Current estimates derived from small samples or uncontrolled survey data suggest that approximately 40% of POTS patients experience migraine, 20–30% meet the diagnostic criteria for hypermobile Ehlers-Danlos syndrome (Miller et al., 2020; Roma et al., 2018), and about 15% carry a diagnosis of a co-morbid autoimmune disease.”
From Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 (2021) · cites this paper as Roma et al., 2018
Orthostatic intolerance and tachycardia can be found in up to 40% of patients with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome.
“Conversely, orthostatic intolerance and tachycardia can be found in up to 40% of patients with hypermobility spectrum disorder or hypermobile Ehlers-Danlos Syndrome (Miller et al., 2020; Roma et al., 2018).”
From Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 (2021) · cites this paper as Roma et al., 2018
Many conditions such as mast cell activation disorders, Ehlers-Danlos syndrome, deconditioning, and genetic mutations of norepinephrine transporters coexist with POTS, and their downstream effects funnel into the three principal pathophysiologic mechanisms.
“While many conditions, such as mast cell activation disorders (9), Ehlers-Danlos syndrome (10, 11), deconditioning (12), and genetic mutations of norepinephrine transporters (13), coexist with POTS, their downstream effects also funnel into these three principal pathophysiologic mechanisms.”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [11]
A significant proportion of patients with Ehlers-Danlos syndrome exhibit autonomic dysfunction and orthostatic intolerance.
“A significant proportion of patients with Ehlers-Danlos syndrome exhibit autonomic dysfunction and orthostatic intolerance (11).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [11]
In Ehlers-Danlos syndrome, characteristic POTS symptoms can be found in up to 40% of patients, and onset is typically not precipitated by viral infection.
“In EDS, characteristic POST symptoms can be found in up to 40% of patients and the onset is typically not precipitated by viral infection [60].”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [60]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Claim about all larger studies conflicts with a reported null comparison
MinorThe summary says every study with more than 10 patients found statistically significant increases, yet the paper later describes a 21-patient study that found no difference in orthostatic intolerance.
“Nonetheless, in all studies with > 10 patients, the data are consistent with clinically important and statistically signi fi cant increases in the prevalence of orthostatic symptoms and objective hemodynamic abnormalities in those with joint hypermobility or EDS”
“In a retrospective review of pediatric patients with chronic functional pain disorders, 11 with JHS and 10 without, there were no di ff erences in migraines or other co-morbid disorders including orthostatic intolerance.”
The stated range of hemodynamic abnormalities excludes a reported study
MinorThe summary gives an upper prevalence of 80%, but the earlier account says all 12 patients in the Rowe study had either POTS or isolated neurally mediated hypotension.
“Hemodynamic abnormalities are identi fi ed in 56 -80% of JH/EDS patients in published studies”
“Ten patients met criteria for POTS, 7 of whom also developed neurally mediated hypotension (NMH) at a later point in the test. Two further patients had isolated NMH.”
Valsalva noncompletion percentage uses the wrong denominator
MinorThe study group contains 35 adults, so 13 people represent 37.1%, not 31.4%.
Reported 31.4 · recomputed 37.142857
“Celletti and colleagues investigated cardiovascular autonomic involvement in JHS or hypermobile EDS with a group of 35 adults (29 female; mean age 35 ± 14 years) (Celletti et al., 2017).”
Classical EDS is described as requiring generalized hypermobility despite an alternative criterion
MinorThe prose says both classical and hypermobile EDS require generalized joint hypermobility. Table 1 instead allows classical EDS to be diagnosed using three minor criteria in its place.
“While both conditions require evidence of generalized joint hypermobility, the degree of skin hyperextensibility is substantial in the classical form and relatively mild in the hypermobile form.”
“Signi fi cant skin hyperextensibility and atrophic scarring Plus either: Generalized joint hypermobility a Or - 3 of the following 9 minor criteria:”
The citation lists haven’t been fetched yet
References 61 · Cited by 133
Research works printed but not linked: 26
- Barron, 2002, Joint hypermobility is more common in children with chronic fatigue syndrome than in healthy controls, J. Pediatr., 141, 421, 10.1067/mpd.2002.127496 · DOI
- Beighton, 1973, Articular hypermobility in an African population, Ann. Rheum. Dis., 32, 413, 10.1136/ard.32.5.413 · DOI · Paper page
- Beighton, 1998, Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997, Am. J. Med. Genet., 77, 31, 10.1002/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O · DOI · Paper page
- Blitshteyn, 2017, Cardiovascular testing in patients with postural tachycardia syndrome and Ehlers-Danlos syndrome type III, Clin. Auton. Res., 27, 117, 10.1007/s10286-017-0397-7 · DOI
- Byers, 2017, Diagnosis, natural history and management in vascular Ehlers-Danlos syndrome, Am. J. Med. Genet., 175, 40, 10.1002/ajmg.c.31553 · DOI · Paper page
- Castori, 2012, Surgical recommendations in Ehlers-Danlos syndrome(s) need patient classification: the example of Ehlers-Danlos syndrome hypermobility type (a.k.a. joint hypermobility syndrome), Dig. Surg., 29, 453, 10.1159/000346068 · DOI
- Cheng, 2016, Cardiovascular profile in postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome type III, Clin. Auton. Res., 27, 113, 10.1007/s10286-016-0392-4 · DOI
- De Coster, 2005, Generalized joint hypermobility and temporomandibular disorders: inherited connective tissue disease as a model with maximum expression, J. Orofac. Pain, 19, 47
- De Wandele, 2014, Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: a comparative study with two other EDS types, fibromyalgia, and healthy controls, Semin. Arthritis Rheum., 44, 353, 10.1016/j.semarthrit.2014.05.013 · DOI · Paper page
- De Wandele, 2016, Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos syndrome, Rheumatology (Oxford), 55, 1412, 10.1093/rheumatology/kew032 · DOI · Paper page
- Deodato, 2006, Predisposition for temporomandibular joint disorders: loose ligaments, Cranio, 24, 179, 10.1179/crn.2006.029 · DOI
- Durham, 2015, Painful temporomandibular disorders are common in patients with postural orthostatic tachycardia syndrome and impact significantly upon quality of life, J. Oral Facial Pain Headache, 29, 152, 10.11607/ofph.1396 · DOI · Paper page
- Grahame, 2000, The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS), J. Rheumatol., 27, 1777
- Henderson, 2017, Neurological and spinal manifestations of the Ehlers–Danlos syndromes, Am. J. Med. Genet. C Semin. Med. Genet., 175C, 195, 10.1002/ajmg.c.31549 · DOI · Paper page
- Kanjwal, 2010, Comparative clinical profile of postural orthostatic tachycardia patients with and without joint hypermobility syndrome, Indian Pacing Electrophysiol. J., 10, 173
- Mack, 2010, Orthostatic intolerance and the headache patient, Semin. Pediatr. Neurol., 17, 109, 10.1016/j.spen.2010.04.006 · DOI · Paper page
- Milhorat, 2007, Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and Chiari malformation type I in patients with hereditary disorders of connective tissue, J. Neurosurg. Spine, 7, 601, 10.3171/SPI-07/12/601 · DOI
- Pohl, 1988, Isoproterenol-induced panic attacks, Biol. Psychiatry, 24, 891, 10.1016/0006-3223(88)90224-7 · DOI · Paper page
- Pohl, 1990, Effects of isoproterenol in panic disorder patients after antidepressant treatment, Biol. Psychiatry, 28, 203, 10.1016/0006-3223(90)90575-M · DOI
- Rowe, 1995, Is neurally mediated hypotension an unrecognized cause of chronic fatigue?, Lancet, 345, 623, 10.1016/S0140-6736(95)90525-1 · DOI
- Russek, 2000, Examination and treatment of a patient with hypermobility syndrome, Phys. Ther., 80, 386, 10.1093/ptj/80.4.386 · DOI
- Simmonds, 2007, Hypermobility and the hypermobility syndrome, Man. Ther., 12, 298, 10.1016/j.math.2007.05.001 · DOI
- Simmonds, 2008, Hypermobility and the hypermobility syndrome, part 2: assessment and management of hypermobility syndrome: illustrated via case studies, Man. Ther., 13, e1, 10.1016/j.math.2007.11.001 · DOI
- Stewart, 1999, Orthostatic intolerance in adolescent chronic fatigue syndrome, Pediatrics, 103, 116, 10.1542/peds.103.1.116 · DOI
- Takenaka, 2002, Effects of rapid saline infusion on orthostatic intolerance and autonomic tone after 20 days bed rest, Am. J. Cardiol., 89, 557, 10.1016/S0002-9149(01)02296-2 · DOI · Paper page
- Van Dijk, 2008, Is fatigue in Marfan syndrome related to orthostatic intolerance?, Clin. Auton. Res., 18, 187, 10.1007/s10286-008-0475-y · DOI
- Authors
- Roma, M., Marden, C. L., De Wandele, I., Francomano, C. A., & Rowe, P. C.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Marden, Colleen L.
- Francomano, Clair A.
- Rowe, Peter C.
- Venue
- Autonomic Neuroscience
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 215
- Pages
- 89-96
- ISSN
- 1566-0702 (ISSN-L)
- OpenAlex
- W2789331034
- Cited by
- 133
- References
- 61
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 21 · 2023: 8 · 2022: 21 · 2021: 34 · 2020: 13 · 2019: 8 · 2018: 3
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autonomic Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- postural orthostatic tachycardia syndrome, orthostatic intolerance, Ehlers-Danlos syndrome, joint hypermobility, hereditary connective tissue disorders, autonomic dysfunction, cardiovascular dysfunction, quality of life, orthostatic challenge
- MeSH terms
- Ehlers-Danlos Syndrome, Humans, Joint Instability, Comorbidity, Syncope, Vasovagal, Postural Orthostatic Tachycardia Syndrome
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