Gajarawala, Shilpa

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.

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.