title: Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.
abstract: Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping connective tissue disorders characterized by chronic/recurrent pain, joint instability complications, and minor skin changes. Fatigue and headache are also common, although are not yet considered diagnostic criteria. JHS/EDS-HT is a unexpectedly common condition that remains underdiagnosed by most clinicians and pain specialists. This results in interventions limited to symptomatic and non-satisfactory treatments, lacking reasonable pathophysiologic rationale. In this manuscript the fragmented knowledge on pain, fatigue, and headache in JHS/EDS is presented with review of the available published information and a description of the clinical course by symptoms, on the basis of authors' experience. Pathogenic mechanisms are suggested through comparisons with other functional somatic syndromes (e.g., chronic fatigue syndrome, fibromyalgia, and functional gastrointestinal disorders). The re-writing of the natural history of JHS/EDS-HT is aimed to raise awareness among clinical geneticists and specialists treating chronic pain conditions about pain and other complications of JHS/EDS-HT. Symptoms' clustering by disease stage is proposed to investigate both the molecular causes and the symptoms management of JHS/EDS-HT in future studies.
authors.affiliation: Division of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Castori
authors.forename: Silvia
authors.initials: S
authors.lastname: Morlino
authors.forename: Claudia
authors.initials: C
authors.lastname: Celletti
authors.forename: Giulia
authors.initials: G
authors.lastname: Ghibellini
authors.forename: Michela
authors.initials: M
authors.lastname: Bruschini
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
authors.forename: Carlo
authors.initials: C
authors.lastname: Blundo
authors.forename: Filippo
authors.initials: F
authors.lastname: Camerota
mesh_terms: D004535:Ehlers-Danlos Syndrome / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D005221:Fatigue / Q000150:complications; D006261:Headache / Q000150:complications / Q000503:physiopathology; D006801:Humans; D007593:Joint Instability / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D010146:Pain / Q000209:etiology / Q000503:physiopathology*
keywords: EDS; JHS; disability; fatigue; headache; hypermobility; pain; pathogenesis; prevention; treatment