Rozen, Lincoln E.

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 Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSDs) are heritable connective tissue disorders characterized by widespread fragile soft connective tissue affecting the skin, ligaments, joints, vasculature, and internal organs. Although hEDS and HSD are autosomal-dominant conditions and would be expected to display a 1:1 sex ratio, studies report higher prevalence in women. Objectives The purpose of this exploratory study was to determine whether self-reported sexual problems differed between females and males diagnosed with hEDS or HSD compared with controls with chronic pain but no hypermobility. Methods In this exploratory retrospective study, we examined 1,407 patients diagnosed with hEDS or HSD according to the 2017 diagnostic criteria for eight indicators of sexual problems based on a validated screening tool. Results Patients in each diagnosis primarily self-reported as White, non-Hispanic females (90%). Of the 1,407 patients who attended the EDS Clinic, 976 (69%) were diagnosed with HSD, 240 (17%) with hEDS, and 191 (14%) were chronic pain controls with neither diagnosis. For HSD, 937 (96%) were females vs. 39 (4%) males (24:1 females to males), while for hEDS, 210 (88%) were females vs. 30 (13%) males (7:1 females to males), and controls were 165 (86%) females vs. 26 (14%) males (6:1 females to males). Females with hEDS reported significantly higher rates of sexual issues than chronic pain controls, including sexual problems (69%, p = 0.018), problems with sexual interest (41%, p = 0.023), sexual pain (45%, p = 0.006), and orgasm difficulty (34%, p = 0.022) compared with males with hEDS or males or females with HSD. In contrast, males diagnosed with hEDS did not report any sexual problems over controls, and males and females diagnosed with HSD reported only one issue—more problems with sexual interest—compared with controls (females p = 0.019, males p = 0.018). However, the small number of males in this study limits conclusions that can be drawn for them. Conclusions This study is unique because we examine sex differences in sexual problems in patients with hEDS and HSD. Our findings indicate a higher percentage of sexual problems in females with hEDS than chronic pain controls without hypermobility, but this was not observed for females with HSD.