Pain in Ehlers-Danlos syndromes: manifestations, therapeutic strategies and future perspectives

Introduction: Ehlers-Danlos syndrome (EDS) groups together an increasing number of hereditary soft connective tissue disorders. Among the most common variants, the hypermobility type emerges as the most problematic, due to clinical similarities with the joint hypermobility syndrome, strong association with pain and lack of molecular confirmatory tests. To date, chronic pain and the related physical disability are the most relevant clinical issues in the long-term management of EDS.Areas covered: A literature review was carried out covering all known pain manifestations, i.e. musculoskeletal pain, neuropathic pain, central sensitization, headache and visceral pain, in EDS. The natural history of pain, as well as other critical issues, i.e. heterogeneity, clinical approach and evolving phenotype, of EDS are also addressed. All available data on therapeutic strategies for pain in EDS are extensively reported.Expert opinion: Multidisciplinarity emerges as an undeniable prerequisite for the management of the complex EDS patient reporting pain. All available therapeutic resources, comprising painkillers, physical and psychological therapies, and surgery, show a low evidence of efficacy in the long-term treatment of pain. Education and early diagnosis are primary resources for secondary and tertiary prevention. Novel drug therapies could be developed considering the potential role of a dysfunctional extracellular matrix on pain modulation in EDS.