Fatigue in Ehlers-Danlos Syndromes

An overview of fatigue and associated conditions in hypermobile EDS, hypermobility spectrum disorder, as well as prevalence data in other subtypes from other studies.

Symptoms of dysautonomia were very common, with fatigue, dizziness, and brain fog being the most frequently reported. Heart palpitations and thermoregulatory dysfunction were also common, indicating significant autonomic involvement in both groups. Despite the high burden of symptoms, many hEDS participants and most HSD participants reported not having a formal autonomic diagnosis. The widespread occurrence of sleep disturbances exacerbates pain, fatigue, and cognitive function, underscoring the necessity for targeted interventions to enhance sleep.

More than two-thirds of participants indicated an event prior to the onset of symptoms or an increase in symptom severity, such as puberty, viral infections, physical trauma, or pregnancy. These results support the theory that environmental factors, alongside genetic predisposition, might play a role in the onset of hEDS and HSD and/or the progression of the disease. The connection between viral infections and worsening symptoms further suggests a possible link between hEDS, immune dysregulation, and post-viral syndromes like long COVID and ME/CFS.

References:

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Ritelli, M., Venturini, M., Cinquina, V., Chiarelli, N., & Colombi, M. (2020). Multisystemic manifestations in a cohort of 75 classical Ehlers-Danlos syndrome patients: natural history and nosological perspectives. Orphanet journal of rare diseases, 15(1), 197. https://doi.org/10.1186/s13023-020-01470-0

Daylor, V., Griggs, M., Weintraub, A., Byrd, R., Petrucci, T., Huff, M., Byerly, K., Fenner, R., Severance, S., Griggs, C., Sharma, A., Atwal, P., Kautz, S. A., Shapiro, S., Youkhana, K., Lavallee, M., Wilkerson, A., Nichols, M., Snyder, A., ... Norris, R. A. (2025). Defining the Chronic Complexities of hEDS and HSD: A Global Survey of Diagnostic Challenges, Life-Long Comorbidities, and Unmet Needs. Journal of Clinical Medicine, 14(16), 5636. https://doi.org/10.3390/jcm14165636