To the Editor:

Thank you for the opportunity to respond to the Letter to the Editor entitled “Response to clinical and genetic aspects of Ehlers-Danlos syndrome, classic type” by Williams. We agree with Dr. Williams that pain is a clinically important manifestation of Ehlers-Danlos syndrome (EDS). However, we would like to take the opportunity to reply with a few comments.

First, we would like to point out that only few studies have addressed pain in EDS. Moreover, the available studies are limited in size and scope and relate mostly to patients with EDS, hypermobility type. Specific findings in patients with classic EDS are not well documented.1–4 Moreover, no evidence-based information on pain management in patients with classic or other types of EDS is currently available.

Second, the pathophysiologic basis of chronic pain in EDS is not well understood. In our clinical experience, no good correlation exists between the degree of hypermobility and the severity of pain. For example, it is our experience that patients with classic EDS often do not suffer from chronic pain, despite presence of severe joint hyperlaxity, whereas patients with EDS, hypermobility type, can suffer from chronic and progressive disabling pain, even if the joint hypermobility is limited. A recent study from Voermans et al.3 confirms our observation that chronic pain is more prevalent and severe in the hypermobility than the classic type of EDS, suggesting that factors other than the degree of joint hypermobility contribute to the pain.

Since this review covers the classic, and not the hypermobility type of EDS, we did not expand too much on the discussion of pain. Nevertheless, we fully agree with Dr. Williams that all patients with EDS should be asked about pain as a routine part of their initial evaluation and that multidisciplinary treatment of pain should be a prominent aspect of symptomatic management of patients with EDS. Studies addressing prevalence, pathophysiology, and treatment strategies of pain in all subtypes of EDS are urgently needed to improve care of patients with EDS.