Background & Aims

Ehlers-Danlos Syndrome (EDS) is a cluster of genetic disorders associated with connective tissue problems, with pain being a common symptom [1, 2, 3]. The multi-faceted nature of EDS presents challenges for accurate diagnosis, as different classifications and other disorders of connective tissue often exhibit overlapping physical symptoms, manifestations, and features like joint hypermobility, joint subluxation and dislocation, skin hyperextensibility and fragility, easy bruising, respiratory symptoms, and dysautonomia [4]. Previous research examining one classification of EDS, hypermobile Ehlers-Danlos Syndrome (hEDS), and a related disorder of connective tissue, Generalized Hypermobility Spectrum Disorder (G-HSD), found no differences in pain intensity or pain interference [5]. The current research aims to further explore the prevalence of self-reported pain conditions in individuals diagnosed with hEDS and G-HSD, and to compare scores on autonomic dysfunction (dysautonomia).

Methods

A total of 491 patients diagnosed with hEDS (n=81) and G-HSD (n=410) were examined from the GoodHope EDS Clinic retrospective database at Toronto General Hospital. Chi-square tests compared self-report responses (either Yes/No) to questions regarding the presence of irritable bowel syndrome, migraines, abdominal pain, osteoporosis, fibromyalgia, and arthritis. Responses on the six domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor) of the Composite Autonomic Symptom Score (COMPASS) were compared with independent t-tests. P < 0.05 is considered statistically significant.

Results

Patients diagnosed with hEDS and G-HSD did not differ with respect to the presence of various self-reported pain symptoms and conditions, all p’s > 0.05. Bladder-related dysautonomia scores were significantly higher in patients with G-HSD than in patients with hEDS, M = -0.82, SE = 0.31, t(194) = -2.048, p = .010. No other domains of autonomic dysfunction were statistically significant.

Conclusions

Previous research in this sample has shown that pain intensity and pain-related interference did not differ between patients with hEDS and G-HSD [5]. Here, we show that patients with G-HSD patients exhibited higher levels of bladder-related autonomic dysfunction than patients with hEDS, which is characterized by a higher frequency of urinary incontinence, urinary hesitancy, and urinary retention over the past year. The two diagnostic groups did not differ in the presence of various symptoms and pain conditions. Examining more specific patient-reported pain conditions and domains of dysautonomia may lend insights into further differentiating between hEDS and G-HSD, and aiding diagnostic clarity based on pain-related and neurodegenerative symptom patterns.

References

1.Aubry-Rozier, B., Schwitzguebel, A., Valerio, F., Tanniger, J., Paquier, C., Berna, C., Hügle, T., & Benaim, C. (2021). Are patients with hypermobile Ehlers–Danlos syndrome or hypermobility spectrum disorder so different? Rheumatology International, 41(10), 1785–1794. https://doi.org/10.1007/s00296-021-04968-3
2.Malfait, F., Colman, M., Vroman, R., De Wandele, I., Rombaut, L., Miller, R. E., Malfait, A.-M., & Syx, D. (2021). Pain in the Ehlers–Danlos syndromes: Mechanisms, models, and challenges. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 187(4), 429–445. https://doi.org/10.1002/ajmg.c.31950
3.Mittal, N., Mina, D. S., McGillis, L., Weinrib, A., Slepian, P. M., Rachinsky, M., Buryk-Iggers, S., Laflamme, C., Lopez-Hernandez, L., Hussey, L., Katz, J., McLean, L., Rozenberg, D., Liu, L., Tse, Y., Parker, C., Adler, A., Charames, G., Bleakney, R., … Clarke, H. (2021). The GoodHope Ehlers Danlos Syndrome Clinic: Development and implementation of the first interdisciplinary program for multi-system issues in connective tissue disorders at the Toronto General Hospital. Orphanet Journal of Rare Diseases, 16(1), 357. https://doi.org/10.1186/s13023-021-01962-7
4.Malfait, F., Francomano, C., Byers, P., Belmont, J., Berglund, B., Black, J., Bloom, L., Bowen, J. M., Brady, A. F., Burrows, N. P., Castori, M., Cohen, H., Colombi, M., Demirdas, S., De Backer, J., De Paepe, A., Fournel?Gigleux, S., Frank, M., Ghali, N., … Tinkle, B. (2017). The 2017 international classification of the Ehlers–Danlos syndromes. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 175(1), 8–26. https://doi.org/10.1002/ajmg.c.31552
5.Daly, C., Axenova, K., Katz, J., Clarke, H., Slepian, M., McCarthy, M., Mittal., N., & McGillis, L. (2024). Toward a better understanding of pain severity, pain interference and symptoms of dysphoria in Ehlers Danlos Syndrome. Book of Posters, Canadian Journal of Pain. https://doi.org/10.1080/24740527.2023.2251871
6.Malfait, F., Castori, M., Francomano, C. A., Giunta, C., Kosho, T., & Byers, P. H. (2020). The Ehlers-Danlos syndromes. Nature reviews. Disease primers, 6(1), 64. https://doi.org/10.1038/s41572-020-0194-9
7.McGillis, L., Mittal, N., Santa Mina, D., So, J., Soowamber, M., Weinrib, A., Soever, L., Rozenberg, D., Liu, L., Tse, Y., Katz, J., Charames, G. S., Murphy, K., Vadas, P., Slepian, M. P., Walsh, S., Wilson, L., Adler, A., Franzese, A., … Clarke, H. (2020). Utilization of the 2017 diagnostic criteria for hEDS by the Toronto GoodHope Ehlers Danlos syndrome clinic: A retrospective review. American Journal of Medical Genetics Part A, 182(3), 484–492. https://doi.org/10.1002/ajmg.a.61459
8.Terry, R. H., Palmer, S. T., Rimes, K. A., Clark, C. J., Simmonds, J. V., & Horwood, J. P. (2015). Living with joint hypermobility syndrome: Patient experiences of diagnosis, referral and self-care. Family Practice, 32(3), 354–358. https://doi.org/10.1093/fampra/cmv026

Presenting Author

Kristina Axenova

Poster Authors

Kristina Axenova

OTHR

York University

Lead Author

E-mail

Charly Daly

York Univeristy

Lead Author

E-mail

Molly McCarthy

Ph.D.

Toronto General Hospital

Lead Author

E-mail

Maxim Rachinsky

MD

Toronto General Hospital

Lead Author

E-mail

Tania Di Renna

TAPMI

Lead Author

E-mail

Praveen Ganty

University Health Network

Lead Author

E-mail

Dmitry Rozenberg

MD

Toronto General Hospital

Lead Author

E-mail

Colleen Parker

MD

University Health Network

Lead Author

E-mail

Yvonne Tse

MD

Toronto General Hospital

Lead Author

E-mail

Louis Liu

MD

Toronto General Hospital

Lead Author

E-mail

Nimish Mittal

MD

Toronto General Hospital

Lead Author

E-mail

Hance Clarke

MD

University Health Network, University of Toronto

Lead Author

E-mail

Joel Katz

PhD

York University

Lead Author

E-mail

Max Slepian

Toronto General Hospital, University Health Network

Lead Author

E-mail

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Rheumatology, Arthritis, and Other