Chronic pain in hypermobility syndrome and Ehlers-Danlos syndrome (hypermobility type): it is a challenge

Mark C Scheper, Janneke E de Vries, Jeanine Verbunt, Raoul Hh Engelbert, Mark C Scheper, Janneke E de Vries, Jeanine Verbunt, Raoul Hh Engelbert

Abstract

Generalized joint hypermobility (GJH) is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in ≥4 joints over a period ≥3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS) may be diagnosed. In addition, GJH is also a clinical sign that is frequently present in hereditary diseases of the connective tissue, such as the Marfan syndrome, osteogenesis imperfecta, and the Ehlers-Danlos syndrome. However, within the Ehlers-Danlos spectrum, a similar subcategory of patients having similar clinical features as HMS but lacking a specific genetic profile was identified: Ehlers-Danlos syndrome hypermobility type (EDS-HT). Researchers and clinicians have struggled for decades with the highly diverse clinical presentation within the HMS and EDS-HT phenotypes (Challenge 1) and the lack of understanding of the pathological mechanisms that underlie the development of pain and its persistence (Challenge 2). In addition, within the HMS/EDS-HT phenotype, there is a high prevalence of psychosocial factors, which again presents a difficult issue that needs to be addressed (Challenge 3). Despite recent scientific advances, many obstacles for clinical care and research still remain. To gain further insight into the phenotype of HMS/EDS-HT and its mechanisms, clearer descriptions of these populations should be made available. Future research and clinical care should revise and create consensus on the diagnostic criteria for HMS/EDS-HT (Solution 1), account for clinical heterogeneity by the classification of subtypes within the HMS/EDS-HT spectrum (Solution 2), and create a clinical core set (Solution 3).

Keywords: Ehlers-Danlos hypermobility type; chronic musculoskeletal pain; generalized joint hypermobility; hypermobility syndrome.

Figures

Figure 1
Figure 1
Clinical heterogeneity. Abbreviation: GJH, generalized joint hypermobility.
Figure 2
Figure 2
Potential pathways of chronic pain in GJH-related disorders. Abbreviation: GJH, generalized joint hypermobility.

References

    1. Greenwood NL, Duffell LD, Alexander CM, McGregor AH. Electromyographic activity of pelvic and lower limb muscles during postural tasks in people with benign joint hypermobility syndrome and non hypermobile people. A pilot study. Man Ther. 2011;16(6):623–628.
    1. Kirk JA, Ansell BM, Bywaters EG. The hypermobility syndrome. Musculoskeletal complaints associated with generalized joint hypermobility. Ann Rheum Dis. 1967;26(5):419–425.
    1. Scheper MC, Engelbert RH, Rameckers EA, Verbunt J, Remvig L, Juul-Kristensen B. Children with generalised joint hypermobility and musculoskeletal complaints: state of the art on diagnostics, clinical characteristics, and treatment. Biomed Res Int. 2013;2013:121054.
    1. Grahame R. Hypermobility: an important but often neglected area within rheumatology. Nat Clin Pract Rheumatol. 2008;4(10):522–524.
    1. Grahame R, Bird HA, Child A. The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS) J Rheumatol. 2000;27(7):1777–1779.
    1. Remvig L, Jensen DV, Ward RC. Are diagnostic criteria for general joint hypermobility and benign joint hypermobility syndrome based on reproducible and valid tests? A review of the literature. J Rheumatol. 2007;34(4):798–803.
    1. Juul-Kristensen B, Rogind H, Jensen DV, Remvig L. Inter-examiner reproducibility of tests and criteria for generalized joint hypermobility and benign joint hypermobility syndrome. Rheumatology. 2007;46(12):1835–1841.
    1. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK) Am J Med Genet. 1998;77(1):31–37.
    1. Malfait F, Hakim AJ, De Paepe A, Grahame R. The genetic basis of the joint hypermobility syndromes. Rheumatology. 2006;45(5):502–507.
    1. De Paepe A, Malfait F. The Ehlers-Danlos syndrome, a disorder with many faces. Clin Genet. 2012;82(1):1–11.
    1. Grahame R, Hakim AJ. Hypermobility. Curr Opin Rheumatol. 2008;20(1):106–110.
    1. Tinkle BT, Bird HA, Grahame R, Lavallee M, Levy HP, Sillence D. The lack of clinical distinction between the hypermobility type of Ehlers-Danlos syndrome and the joint hypermobility syndrome (aka hypermobility syndrome) Am J Med Genet A. 2009;149A(11):2368–2370.
    1. Wordsworth P, Ogilvie D, Smith R, Sykes B. Joint mobility with particular reference to racial variation and inherited connective tissue disorders. Br J Rheumatol. 1987;26(1):9–12.
    1. Murray KJ. Hypermobility disorders in children and adolescents. Best Pract Res Clin Rheumatol. 2006;20(2):329–351.
    1. Mallorquí-Bagué N, Bulbena A, Roé-Vellvé N, et al. Emotion processing in joint hypermobility: a potential link to the neural bases of anxiety and related somatic symptoms in collagen anomalies. Eur Psychiatry. 2015;30(4):454–458.
    1. Scheper MC, de Vries JE, de Vos R, Verbunt J, Nollet F, Engelbert RH. Generalized joint hypermobility in professional dancers: a sign of talent or vulnerability? Rheumatology. 2013;52(4):651–658.
    1. Scheper MC, de Vries JE, Juul-Kristensen B, Nollet F, Engelbert RH. The functional consequences of generalized joint hypermobility: a cross-sectional study. BMC Musculoskelet Disord. 2014;15:243.
    1. Day H, Koutedakis Y, Wyon MA. Hypermobility and dance: a review. Int J Sports Med. 2011;32(7):485–489.
    1. Foley EC, Bird HA. Hypermobility in dance: asset, not liability. Clin Rheumatol. 2013;32(4):455–461.
    1. Palmer S, Bailey S, Barker L, Barney L, Elliott A. The effectiveness of therapeutic exercise for joint hypermobility syndrome: a systematic review. Physiotherapy. 2014;100(3):220–227.
    1. Pacey V, Tofts L, Wesley A, Collins F, Singh-Grewal D. Joint hypermobility syndrome: a review for clinicians. J Paediatr Child Health. 2014;51(4):373–380.
    1. Grahame R. Heritable disorders of connective tissue. Baillieres Best Pract Res Clin Rheumatol. 2000;14(2):345–361.
    1. Remvig L, Engelbert RH, Berglund B, et al. Need for a consensus on the methods by which to measure joint mobility and the definition of norms for hypermobility that reflect age, gender and ethnic-dependent variation: is revision of criteria for joint hypermobility syndrome and Ehlers-Danlos syndrome hypermobility type indicated? Rheumatology. 2011;50(6):1169–1171.
    1. Pacey V, Adams RD, Tofts L, Munns CF, Nicholson LL. Joint hypermobility syndrome subclassification in paediatrics: a factor analytic approach. Arch Dis Child. 2015;100(1):8–13.
    1. De Wandele I, Rombaut L, Malfait F, De Backer T, De Paepe A, Calders P. Clinical heterogeneity in patients with the hypermobility type of Ehlers-Danlos syndrome. Res Dev Disabil. 2013;34(3):873–881.
    1. Grahame R. Hypermobility – not a circus act. Int J Clin Pract. 2000;54(5):314–315.
    1. Hogan KA, Gross RH. Overuse injuries in pediatric athletes. Orthop Clin North Am. 2003;34(3):405–415.
    1. De Wandele I, Rombaut L, Leybaert L, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome. Semin Arthritis Rheum. 2014;44(1):93–100.
    1. De Wandele I, Calders P, Peersman W, et al. Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: a comparative study with two other EDS types, fibromyalgia, and healthy controls. Semin Arthritis Rheum. 2014;44(3):353–361.
    1. Ferrell WR, Tennant N, Sturrock RD, et al. Amelioration of symptoms by enhancement of proprioception in patients with joint hypermobility syndrome. Arthritis Rheum. 2004;50(10):3323–3328.
    1. Rombaut L, Malfait F, De Wandele I, et al. Balance, gait, falls, and fear of falling in women with the hypermobility type of Ehlers-Danlos syndrome. Arthritis Care Res (Hoboken) 2011;63(10):1432–1439.
    1. Fatoye FA, Palmer S, van der Linden ML, Rowe PJ, Macmillan F. Gait kinematics and passive knee joint range of motion in children with hypermobility syndrome. Gait Posture. 2011;33(3):447–451.
    1. Falkerslev S, Baagø C, Alkjær T, et al. Dynamic balance during gait in children and adults with generalized joint hypermobility. Clin Biomech. 2013;28(3):318–324.
    1. Celletti C, Galli M, Cimolin V, Castori M, Albertini G, Camerota F. Relationship between fatigue and gait abnormality in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type. Res Dev Disabil. 2012;33(6):1914–1918.
    1. Rigoldi C, Galli M, Cimolin V, et al. Gait strategy in patients with Ehlers-Danlos syndrome hypermobility type and Down syndrome. Res Dev Disabil. 2012;33(5):1437–1442.
    1. Nikolajsen H, Larsen PK, Simonsen EB, et al. Gait pattern in 9–11-year-old children with generalized joint hypermobility compared with controls; a cross-sectional study. BMC Musculoskelet Disord. 2013;14:341.
    1. Simonsen EB, Tegner H, Alkjaer T, et al. Gait analysis of adults with generalised joint hypermobility. Clin Biomech. 2012;27(6):573–577.
    1. Junge T, Wedderkopp N, Thorlund JB, Sogaard K, Juul-Kristensen B. Altered knee joint neuromuscular control during landing from a jump in 10–15year old children with generalised joint hypermobility. A substudy of the CHAMPS-study Denmark. J Electromyogr Kinesiol. 2015;25(3):501–507.
    1. Rombaut L, Malfait F, De Wandele I, et al. Muscle-tendon tissue properties in the hypermobility type of Ehlers-Danlos syndrome. Arthritis Care Res (Hoboken) 2012;64(5):766–772.
    1. Magnusson SP, Julsgaard C, Aagaard P, et al. Viscoelastic properties and flexibility of the human muscle-tendon unit in benign joint hypermobility syndrome. J Rheumatol. 2001;28(12):2720–2725.
    1. Smith TO, Jerman E, Easton V, et al. Do people with benign joint hypermobility syndrome (BJHS) have reduced joint proprioception? A systematic review and meta-analysis. Rheumatol Int. 2013;33(11):2709–2716.
    1. Russek LN. Hypermobility syndrome. Phys Ther. 1999;79(6):591–599.
    1. Sahin N, Baskent A, Ugurlu H, Berker E. Isokinetic evaluation of knee extensor/flexor muscle strength in patients with hypermobility syndrome. Rheumatol Int. 2008;28(7):643–648.
    1. Rombaut L, Malfait F, De Wandele I, et al. Muscle mass, muscle strength, functional performance, and physical impairment in women with the hypermobility type of Ehlers-Danlos syndrome. Arthritis Care Res (Hoboken) 2012;64(10):1584–1592.
    1. Engelbert RH, van Bergen M, Henneken T, Helders PJ, Takken T. Exercise tolerance in children and adolescents with musculoskeletal pain in joint hypermobility and joint hypomobility syndrome. Pediatrics. 2006;118(3):e690–e696.
    1. Fatoye F, Palmer S, Macmillan F, Rowe P, van der Linden M. Proprioception and muscle torque deficits in children with hypermobility syndrome. Rheumatology. 2009;48(2):152–157.
    1. Scheper M, Vries J, Beelen A, Vos R, Nollet F, Engelbert R. Generalized joint hypermobility, muscle strength and physical function in healthy adolescents and young adults. Curr Rheumatol Rev. 2015;10(2):117–125.
    1. Ferrell WR, Tennant N, Baxendale RH, Kusel M, Sturrock RD. Musculoskeletal reflex function in the joint hypermobility syndrome. Arthritis Rheum. 2007;57(7):1329–1333.
    1. Holla JF, van der Leeden M, Peter WF, et al. Proprioception, laxity, muscle strength and activity limitations in early symptomatic knee osteoarthritis: results from the CHECK cohort. J Rehabil Med. 2012;44(10):862–868.
    1. Rombaut L, Scheper M, De Wandele I, et al. Chronic pain in patients with the hypermobility type of Ehlers-Danlos syndrome: evidence for generalized hyperalgesia. Clin Rheumatol. 2014;34(6):1121–1129.
    1. Clark CK, Khattab A, Carr E. Chronic widespread pain and neurophysiological symptoms in joint hypermobility syndrome (JHS) Int J Ther Rehabil. 2014;21(2):9.
    1. Hakim AJ, Grahame R, Norris P, Hopper C. Local anaesthetic failure in joint hypermobility syndrome. J R Soc Med. 2005;98(2):84–85.
    1. Rombaut L, Malfait F, De Wandele I, et al. Medication, surgery, and physiotherapy among patients with the hypermobility type of Ehlers-Danlos syndrome. Arch Phys Med Rehabil. 2011;92(7):1106–1112.
    1. Nijs J, Malfliet A, Ickmans K, Baert I, Meeus M. Treatment of central sensitization in patients with ‘unexplained’ chronic pain: an update. Expert Opin Pharmacother. 2014;15(12):1671–1683.
    1. Vlaeyen JW, Linton SJ. Fear-avoidance and its consequences in chronic musculoskeletal pain: a state of the art. Pain. 2000;85(3):317–332.
    1. Leeuw M, Goossens ME, Linton SJ, Crombez G, Boersma K, Vlaeyen JW. The fear-avoidance model of musculoskeletal pain: current state of scientific evidence. J Behav Med. 2007;30(1):77–94.
    1. Vlaeyen JW, Linton SJ. Fear-avoidance model of chronic musculoskeletal pain: 12 years on. Pain. 2012;153(6):1144–1147.
    1. Simons LE, Kaczynski KJ. The fear avoidance model of chronic pain: examination for pediatric application. J Pain. 2012;13(9):827–835.
    1. Eccleston C, Wastell S, Crombez G, Jordan A. Adolescent social development and chronic pain. Eur J Pain. 2008;12(6):765–774.
    1. Cohen LL, Vowles KE, Eccleston C. The impact of adolescent chronic pain on functioning: disentangling the complex role of anxiety. J Pain. 2010;11(11):1039–1046.
    1. Moreno-Peral P, Conejo-Cerón S, Motrico E, et al. Risk factors for the onset of panic and generalised anxiety disorders in the general adult population: a systematic review of cohort studies. J Affect Disord. 2014;168:337–348.
    1. Bulbena A, Gago J, Pailhez G, Sperry L, Fullana MA, Vilarroya O. Joint hypermobility syndrome is a risk factor trait for anxiety disorders: a 15-year follow-up cohort study. Gen Hosp Psychiatry. 2011;33(4):363–370.
    1. Remvig L, Flycht L, Christensen KB, Juul-Kristensen B. Lack of consensus on tests and criteria for generalized joint hypermobility, Ehlers-Danlos syndrome: hypermobile type and joint hypermobility syndrome. Am J Med Genet A. 2014;164A(3):591–596.
    1. El-Metwally A, Salminen JJ, Auvinen A, Macfarlane G, Mikkelsson M. Risk factors for development of non-specific musculoskeletal pain in preteens and early adolescents: a prospective 1-year follow-up study. BMC Musculoskelet Disord. 2007;8:46.
    1. El-Metwally A, Salminen JJ, Auvinen A, Kautiainen H, Mikkelsson M. Lower limb pain in a preadolescent population: prognosis and risk factors for chronicity – a prospective 1- and 4-year follow-up study. Pediatrics. 2005;116(3):673–681.
    1. El-Metwally A, Salminen JJ, Auvinen A, Kautiainen H, Mikkelsson M. Prognosis of non-specific musculoskeletal pain in preadolescents: a prospective 4-year follow-up study till adolescence. Pain. 2004;110(3):550–559.
    1. Tobias JH, Deere K, Palmer S, Clark EM, Clinch J. Joint hypermobility is a risk factor for musculoskeletal pain during adolescence: findings of a prospective cohort study. Arthritis Rheum. 2013;65(4):1107–1115.
    1. Medeiros HB, de Araujo DS, de Araujo CG. Age-related mobility loss is joint-specific: an analysis from 6,000 flexitest results. Age. 2013;35(6):2399–2407.
    1. Remvig L, Duhn PH, Ullman S, et al. Skin extensibility and consistency in patients with Ehlers-Danlos syndrome and benign joint hypermobility syndrome. Scand J Rheumatol. 2009;38(3):227–230.
    1. Remvig L, Duhn P, Ullman S, et al. Skin signs in Ehlers-Danlos syndrome: clinical tests and para-clinical methods. Scand J Rheumatol. 2010;39(6):511–517.
    1. Voermans NC, Knoop H, van de Kamp N, Hamel BC, Bleijenberg G, van Engelen BG. Fatigue is a frequent and clinically relevant problem in Ehlers-Danlos syndrome. Semin Arthritis Rheum. 2010;40(3):267–274.
    1. Atkinson HL, Nixon-Cave K. A tool for clinical reasoning and reflection using the international classification of functioning, disability and health (ICF) framework and patient management model. Phys Ther. 2011;91(3):416–430.
    1. Chien CW, Rodger S, Copley J, Skorka K. Comparative content review of children’s participation measures using the International Classification of Functioning, Disability and Health-Children and Youth. Arch Phys Med Rehabil. 2014;95(1):141–152.
    1. Raghavendra P, Bornman J, Granlund M, Bjorck-Akesson E. The World Health Organization’s International Classification of Functioning, Disability and Health: implications for clinical and research practice in the field of augmentative and alternative communication. Augment Altern Commun. 2007;23(4):349–361.
    1. Wilson GC, Quillin RC, 3rd, Hanseman DJ, Lewis JD, Edwards MJ, Shaughnessy EA. Incidence and predictors of neuropathic pain following breast surgery. Ann Surg Oncol. 2013;20(10):3330–3334.

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