Knight, Dacre R T

Abstract Background Wide-spread mast cell (MC)-associated symptoms and MC activation syndrome (MCAS) are often reported in patients with hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). The goal of this study was to develop a novel MC score based on 11 self-reported MC-related conditions with clinical and research utility to better understand MC symptoms in hEDS and HSD patients. Methods From November 1, 2019, to June 13, 2025, patients ( n =2,141) filled out an Intake Questionnaire at the Mayo Clinic Florida EDS Clinic that included 11 self-reported questions related to categories of MC-related conditions for a MC score ranging from 0/11 to 11/11. Based on the MC score distribution in hEDS and HSD patients, a MC score of 0-1 was considered a low MC score and ≥5 was considered a high MC score. Symptoms/comorbidities were compared between patients with high vs. low MC scores. Results From the 2,141 hEDS/HSD patients, 535 (25.0%) had a MC score ≥5 (Hi MC). MCAS-specific symptoms such as nausea and vomiting were reported more often in hEDS/HSD patients with a high vs. low MC score ( p <0.0001). Random clinical blood tryptase and urinary MC markers were not elevated in patients with high MC scores ( n =50/group), although high MC scores were found to significantly reduce urinary creatinine levels indicating that the protein used to normalize data was affected by MC activity. In contrast, random blood IgE, tryptase and major basic protein (MBP) by ELISA were increased in patients with high MC scores (e.g., IgE hEDS p =0.0004, HSD p =0.003). Of note, the percentage of patients reporting abuse or post-traumatic stress disorder was nearly doubled in patients with high vs. low MC scores (Abuse and PTSD: hEDS p < 0.0001; HSD p < 0.0001). Overall, 109/135 (80.7%) in hEDS and 129/135 (95.6%) in HSD reported more symptoms/comorbidities if they had a high MC score. Conclusions We found that hEDS/HSD patients with high MC scores self-reported more widespread symptoms/comorbidities and higher MC-related blood markers than patients with low MC scores indicating the utility of this tool to evaluate the level of widespread MC activity in hEDS, HSD and other patients.

Background/Objective: It remains unknown whether patients with the more common forms of hypermobility carry an elevated risk for the development of intracranial/cervical artery abnormalities. The objective of this study was to determine the prevalence of unruptured intracranial aneurysms, spontaneous cervical artery dissections, and fibromuscular dysplasia in patients with hypermobile Ehlers–Danlos Syndrome (hEDS) and hypermobility spectrum disorders (HSD) who presented to an academic headache clinic. Methods: This is a retrospective cohort study. We used an electronic medical record to look for all patients seen at the Mayo Clinic Florida Headache Center and EDS Clinic between 2019 and 2025 with a diagnosis of hEDS or HSD and neuroimaging of both the intracranial and cervical arteries. Results: There were 103 patients who met the inclusion criteria. There was no statistically significant difference between hEDS and HSD patients in developing cerebral/cervical arterial anomalies. Of the sample, 95% of the hypermobile patients with abnormal neuroimaging also had migraine. A total of eleven (10.7%) patients (hEDS + HSD) were diagnosed with unruptured intracranial aneurysms. Trends included age less than 50 years, small aneurysms in the anterior circulation, and having migraine with aura. Five (4.8%) patients were diagnosed with spontaneous cervical artery dissection with trends for HSD, over the age of 50 years, vertebral artery involvement and a history of migraine without aura. Six (5.8%) patients were diagnosed with fibromuscular dysplasia with trends for HSD, over the age of 50 years, carotid artery involvement and a history of migraine with aura. Conclusions: This is the first study to identify that patients with the more common type of EDS, HSD and hEDS, and a possible concomitant history of migraine have a heightened risk for the development of unruptured intracranial aneurysms, spontaneous cervical artery dissections, and fibromuscular dysplasia. Our findings suggest the need for targeted screening with intracranial and extracranial arterial imaging for this unique patient population.

Objectives Heritable connective tissue disorders (HCTDs), including hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobile spectrum disorder (HSD), have complex clinical manifestations, but the prevalence of left common iliac vein (LCIV) compression in these groups is not well known. This study aimed to compare the prevalence of significant LCIV compression in patients with hEDS, HSD, and healthy controls. Methods This retrospective, IRB-approved, single-center study analyzed 109 patients (25 hEDS, 64 HSD, 20 controls) who underwent contrast-enhanced abdominal and pelvic CT imaging from 2020 to 2023. LCIV compression was measured on axial CT, with >50% luminal narrowing defined as significant. Statistical analyses included chi-square tests, odds ratios, and t -tests. Interrater reliability was evaluated using intraclass correlation coefficients. Results Significant LCIV compression occurred in 68.0% of hEDS, 65.6% of HSD, and 35.0% of controls ( p = 0.034). Both hEDS ( p = 0.027) and HSD ( p = 0.015) groups had significantly higher compression rates than controls, with no statistically significant difference between the two clinical groups ( p = 0.831). Odds of compression were nearly fourfold greater in hEDS (OR 3.95) and HSD (OR 3.54) compared to controls. Conclusion LCIV compression is significantly more prevalent in patients with hEDS and HSD than in healthy controls, warranting further investigation of its clinical significance.

Abstract Objectives Patients with hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) experience a wide array of symptoms and system disorders. This study aimed to identify whether differences occurred in 115 self-reported symptoms and comorbidities in patients diagnosed with hEDS or HSD. Methods In this study we analysed self-reported data from an EDS Clinic intake questionnaire in patients diagnosed with hEDS, HSD or no hypermobile conditions. Results From 1 November 2019 to 7 March 2024, the EDS Clinic saw 2088 patients. Using the 2017 diagnostic criteria, 66.5% were diagnosed with HSD (n = 1389), 20.3% with hEDS (n = 423), 10.6% with historic HSD (H-HSD) or localized HSD (L-HSD) (n = 256) (hypermobile controls) and 2.6% were not diagnosed with hEDS, HSD, H-HSD or L-HSD (n = 55) (controls). Symptoms/comorbidities that occurred with high prevalence in both hEDS and HSD included joint pain (hEDS 82.0%, HSD 88.9%), allergy (hEDS 77.0%, HSD 77.0%), subluxations (hEDS 71.2%, HSD 72.6%), brain fog (hEDS 70.0%, HSD 74.7%), headache (hEDS 68.1%, HSD 69.1%), anxiety (hEDS 60.3%, HSD 69.3%), depression (hEDS 52.2%, HSD 58.0%), migraine (hEDS 53.7%, HSD 52.5%), nausea (hEDS 54.6%, HSD 59.5%) and constipation (hEDS 53.0%, HSD 57.2%). In contrast, 9/115 (8%) symptoms/comorbidities were self-reported significantly more often in hEDS but 42/115 (37%) in HSD. hEDS patients reported more symptoms that suggest a defect in collagen, such as dislocation, hernias and rectal prolapse, while HSD patients reported more joint, muscle, allergy, neurological, gastrointestinal, sleep and psychological symptoms/comorbidities. Conclusion Although we found an overlap in some symptoms and comorbidities self-reported by hEDS/HSD patients, such as allergy/atopy, headache/migraine and gastrointestinal symptoms, our findings suggest key differences exist between the two diagnoses, suggesting that hEDS and HSD may be distinct conditions.

Objective To report the prevalence and severity of nonpelvic symptoms for patients with venous-origin chronic pelvic pain (VO-CPP) and to describe outcomes after pelvic vein stenting and embolization. Methods We retrospectively reviewed outcomes of 45 women with VO-CPP who underwent treatment with iliac vein stenting and/or embolization. Patients completed symptom-severity questionnaires before and after treatment that assessed for pelvic pain, and multiple other symptoms, including brain fog, anxiety, depression, musculoskeletal pain, fatigue, migraines and more. Results Patient age ranged from 18 to 65 years. The prevalence of common symptoms was as follows: migraines, 69%; brain fog, 76%; anxiety attacks, 58%; excess sweating, 64%; hip pain, 73%; diarrhea, 62%; constipation, 76%; and abdominal bloating, 82%. After treatment, most symptom scores improved by more than 50%; exceptions were excessive sweating (41% improvement) and bloating (47% improvement). Prevalence of individual symptoms that bundle into POTS ranged from 29% to 76%, where symptom improvement ranged from 23% to 59% after treatment. Overlapping individual symptoms characteristic of fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) were present in 64% to 82% of patients and all improved by 49% to 63% after treatment. Conclusions Pelvic venous flow abnormality is linked causally to a spectrum of interrelated symptoms, of which many can be bundled into named syndromes of unknown cause. With catheter- based treatment of pelvic venous pooling, nonpelvic symptom and syndrome scores improved.

Objectives Comorbidities associated with venous origin chronic pelvic pain (VO-CPP) were evaluated pre and post venous treatment to assess change. Materials and methods 45 women with VO-CPP were treated with venous stenting and/or embolization. Four surveys assessed symptoms pre- and post-treatment: IPPS (chronic pelvic pain), PUF (interstitial cystitis), OHQ (dysautonomia), and modified ROME III (IBS). Prevalence of joint hypermobility was investigated. Results Ages were 18–65. Pretreatment, 64% and 49% of women were in the severe range for PUF and OHQ, respectively. 40% and 56% met criteria for IBS and Ehlers-Danlos syndrome/Hypermobility Spectrum Disorder (EDS/HSD), respectively. 17eceived an iliac stent, 5 pelvic embolization, and 23 both. Post-treatment, average scores improved: IPPS (by 55%), PUF (34%), and OHQ (49%). Rome III improved only slightly. Conclusion Pelvic pain, interstitial cystitis, and dysautonomia were frequently found with VO-CPP and improved after venous treatment. EDS/HSD and IBS were common in these women.

ObjectiveThe aim was to study laryngological complaints in patients with hypermobile Ehlers‐Danlos syndrome (hEDS) or hypermobility spectrum disorders (HSD).MethodsA total of 363 patients met inclusion for the study by completing questions related to voice, upper airway, and swallowing between July 7, 2020 and July 13, 2022. Demographic data, voice‐related questions, and hypermobility diagnosis were analyzed retrospectively. From those, 289 patients were diagnosed with hEDS or HSD with 74 that did not meet the diagnostic criteria for either diagnosis serving as controls.ResultsThere were no statistically significant differences between patients with hEDS and HSD regarding Voice Handicap Index (VHI‐10) scores, voice, upper airway, or swallow complaints. However, more hEDS/HSD patients answered positively to the laryngeal dysfunction question versus controls (p = 0.031). 22.5% of hEDS/HSD patients (n = 65) reported hoarseness, of which 52.3% reported hoarseness >2 days/month. 33.9% (n = 98) with hEDS/HSD reported symptoms of dysphagia, and 27.0% (n = 78) reported laryngeal dysfunction symptoms. Controls demonstrated 20.3% prevalence of hoarseness, of which 46.7% reported hoarseness >2 days/month. 24.3% of controls had dysphagia and 14.9% laryngeal dysfunction symptoms. Of the 363 patients, VHI‐10 scores >11 were more likely in patients reporting >2 days of hoarseness/month (p = 0.001) versus those with <2 days of hoarseness/month. There was an increased prevalence of voice, upper airway, and dysphagia symptoms in hEDS/HSD patients compared with previously reported prevalence data in the general population.ConclusionA significant proportion of patients diagnosed with hypermobility due to hEDS or HSD were found to have voice, upper airway, and dysphagia symptoms. These rates are higher than those previously reported in the general population.Level of Evidence3 Laryngoscope, 134:773–778, 2024

Identifying risk factors for post-acute sequelae of COVID-19 (PASC) is important. We conducted a multicenter cross-sectional survey study to define and characterize risk factors for severe COVID-19 in adults (≥18 years) treated at our virtual COVID-19 clinic from March 1, 2020, through March 31, 2021. We assessed patient demographics, symptom types, and persistence, incidence of PASC, and COVID-19–caused hospitalizations. Surveyed patients were also asked to rate their perception of the severity of their acute COVID-19 symptoms. Continuous variables were summarized descriptively. Differences among groups categorized by acute COVID-19 symptom severity level (mild/very mild, moderate, and severe/very severe) were evaluated with the Kruskal–Wallis rank sum test for continuous measures and the Pearson χ 2 test for categorical measures. A total of 3094 adults completed the survey. More respondents with severe/very severe acute COVID-19 symptoms reported having PASC than did those with mild/very mild and moderate acute symptoms. A significantly greater proportion of respondents with PASC were women (68.4% vs 56.7%, p < 0.001), had been hospitalized (12.2% vs 4.4%, p < 0.001), reported having negative psychological COVID-19–related repercussions (39.9% vs 15.3%, p < 0.001), and required more than 1 month to resume normal activities (38.8% vs 12.9%, p < 0.001) than did those without PASC. These findings may improve our understanding of PASC and provide a framework for early recognition of and intervention for patients at higher risk for PASC. Further research is needed to understand the predictors of persistent symptoms after acute SARS-CoV-2 infection and the risk of PASC.