INTRODUCTION — The hypermobile subtype of Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) are among a group of conditions characterized by joint hypermobility and other frequently shared clinical features (table 1). Many of the patients with hEDS and HSD were historically described as having joint hypermobility syndrome (JHS), a term no longer used to classify patients since a major revision of the criteria for JHS and the Ehlers-Danlos syndromes (EDS) in 2017 [1,2].
HSD includes those individuals with a hypermobility-related condition who do not fulfill either the more stringent criteria for hEDS or criteria for another of the hereditary disorders of connective tissue (HDCT) [3,4].
An overview of the management and prognosis of hEDS and HSD in adults and in younger persons is presented here. The epidemiology, pathogenesis, clinical manifestations, and diagnosis of these conditions are described separately. (See "Clinical manifestations and diagnosis of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder".)
Overviews of the clinical manifestations, diagnosis, and management of the other, rarer subtypes of EDS; the clinical manifestations and treatment of Marfan syndrome and Loeys-Dietz syndrome and other related disorders; osteogenesis imperfecta; and Stickler syndrome are presented separately. (See "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes" and "Overview of the management of Ehlers-Danlos syndromes" and "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders" and "Osteogenesis imperfecta: An overview" and "Syndromes with craniofacial abnormalities", section on 'Stickler and Marshall syndromes'.)
TREATMENT
Approach to management — Treatment of patients with hypermobility spectrum disorder (HSD) or hypermobile Ehlers-Danlos syndrome (hEDS) should be individualized, based upon the patient's symptoms, clinical findings, and response to treatment interventions [5-7]. Patients can often be managed effectively by their primary care provider, who should coordinate the patient's individualized multidisciplinary care, including patient education regarding the condition, and referrals for physical and occupational therapy and to medical and surgical specialists, depending upon the patient's clinical manifestations. (See 'Patient education and self-management' below and 'Musculoskeletal manifestations and pain' below and 'Fatigue' below and 'Referral for associated manifestations' below.)
The major elements of management for both HSD and hEDS include [5-7]:
●All patients
•Patient education and instruction in self-management (see 'Patient education and self-management' below)
•Physical and occupation therapy, including exercise, therapy, splinting, and orthoses (see 'Physical and occupational therapy and exercise' below)
●Selected patients and patient groups – Certain patients may require additional interventions for the following:
•Chronic widespread pain – Multidisciplinary management with medication, exercise, and psychosocial measures (see 'Chronic widespread pain' below)
•Anxiety and/or depression – Medical management, psychotherapy, and other behavioral measures (see 'Anxiety and depression' below)
•Fatigue – Medical evaluation and medical and behavioral management of pain, sleep, and autonomic dysfunction, if present (see 'Fatigue' below)
•Specialty referrals may be required for additional management issues affecting different organs and systems, including neurologic, gastrointestinal, genitourinary, hematologic, and neuromuscular manifestations (see 'Referral for associated manifestations' below)
Patients for whom the diagnosis is uncertain, or for whom assistance is needed in overall management, should be referred to an expert in the management of such cases, such as a rheumatologist or clinical geneticist. A clinical geneticist can assist in confirming or excluding a diagnosis of another hereditary disorder of connective tissue (HDCT; eg, Marfan syndrome or rare types of Ehlers-Danlos syndrome [EDS]) or other genetic conditions. (See "Clinical manifestations and diagnosis of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder", section on 'Diagnosis' and "Clinical manifestations and diagnosis of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder", section on 'Differential diagnosis'.)
Most people with joint hypermobility alone, which may affect 10 to 20 percent of the general population to some degree and affect isolated joints or be more generalized, do not experience any problems from the condition; thus, they generally will not require any treatment. (See "Clinical manifestations and diagnosis of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder", section on 'Epidemiology'.)
Patient education and self-management — All patients should receive education regarding the nature of the condition, and we advise interested patients to seek further education, self-help, and supportive advice through national organizations such as The Hypermobility Syndromes Association (HMSA), based in the United Kingdom [8], and The Ehlers-Danlos Society, an international organization registered in the United States and United Kingdom [9]. There are also a number of other national-based charities with helpful local/regional information on their websites.
Musculoskeletal manifestations and pain
Physical and occupational therapy and exercise — We suggest that all patients undergo physical therapy for assistance in the management of the musculoskeletal issues, including use of appropriate exercises, splints, and adaptive devices [10,11]. We refer patients to a physical therapist, when available, who has expertise in the care of hypermobility disorders and related conditions. Patients with significant upper extremity involvement or anatomic abnormalities affecting the feet should be further evaluated and treated by an occupational therapist or podiatrist, respectively.
School-age children with handwriting difficulties should be assessed by an occupational therapist, and those with pronated feet and lower limb pain should be assessed by a podiatrist.
●Therapy and exercise – Patients should participate in physical and occupational therapy and exercise adapted for individuals with joint hypermobility to improve joint stability and strength, avoid injury, and help overcome physical concerns [10,11]. The approach is a global view with a focus on joint protection, muscular rebalancing, strengthening, and joint stabilization, rather than an isolated view of one joint or body region. Physical therapies should take account of the individual's normal range of joint movement, joint instability, risk of soft tissue injury, and poor proprioception. Therapies that may be of benefit include physiotherapy, occupational therapy, and exercise programs such as Pilates and tai chi. Exercise prescription and advice on activities to undertake should be provided by a clinician familiar with the patient and individualized depending on the patient's presentation.
●Splints and orthoses – We use orthotics and splints for improving joint alignment and providing stability in conjunction with physical and occupational therapy and podiatry evaluation. Patients with excessively pronated feet and lower limb pain may benefit from the provision of custom-made supportive in-shoe orthosis.
Chronic widespread pain — Patients with longstanding (over three months) or widespread musculoskeletal pain symptoms may benefit from individual pain management using a multidisciplinary approach of the type advocated for patients with fibromyalgia or chronic neuropathic pain [7,12]. (See "Treatment of fibromyalgia in adults not responsive to initial therapies", section on 'Multidisciplinary treatment programs' and "Initial treatment of fibromyalgia in adults" and "Approach to the management of chronic non-cancer pain in adults".)
The treatment of chronic widespread pain, which should be individualized, is the same as for other conditions with highly similar manifestations, such as fibromyalgia [12]. Pharmacologic treatments may include simple analgesics, such as acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs); and patients may benefit from the use of selected antidepressants, antiseizure medications, and muscle relaxants that are of benefit in the management of chronic pain. Patients may benefit from multidisciplinary pain management programs, including cognitive behavioral therapy. These treatments are described in detail separately. (See "Initial treatment of fibromyalgia in adults" and "Treatment of fibromyalgia in adults not responsive to initial therapies".)
Patients who do not respond adequately to initial measures for pain management should be referred to a specialist team for complex pain management, which includes experts in the use of cognitive behavioral therapy. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Pharmacologic therapy for neuropathic pain, or nociplastic or centralized pain'.)
Treatments for pain appear similarly effective in HSD and hEDS compared with other chronic pain syndromes, both in our experience and that of other experts. There are no randomized trials that have evaluated any differences in outcomes from multidisciplinary pain interventions in complex pain populations with HSD or hEDS compared with those without.
Anxiety and depression — Patients with mood disorders, such as anxiety and/or depression, which may be associated with chronic pain, should be evaluated and managed by experts in the treatment of these conditions. Where possible, such management should be incorporated into multidisciplinary pain management programs [13,14]. (See "Unipolar major depression in adults: Choosing initial treatment" and "Pharmacologic management of chronic non-cancer pain in adults", section on 'Pharmacologic therapy for neuropathic pain, or nociplastic or centralized pain'.)
Fatigue — The potential causes of fatigue in a given patient should be identified and individually addressed [15]. Underlying metabolic or hematologic causes should be managed accordingly. Otherwise, the management of fatigue is primarily the management of pain, sleep patterns, and autonomic dysfunction (see 'Musculoskeletal manifestations and pain' above and "Approach to the adult patient with fatigue" and 'Referral for associated manifestations' below). Individually tailored and closely monitored exercise prescriptions are of value in patients of all ages.
Patients with fatigue who are suspected of an endocrine/metabolic disorder (eg, hypothyroidism, hypoadrenalism) as a potential cause for such symptoms may require referral to an expert in endocrinology.
Referral for associated manifestations — Additional referrals depend upon the clinical manifestation. There is a lack of evidence to support a difference in response to treatment for these associated conditions in patients with hEDS or HSD, and therefore, our approach is to use best-evidence pathways for each in patients without hEDS or HSD. The management of these disorders is described in detail separately.
Conditions that may require further referral may include:
●Orthostasis and other symptoms of possible autonomic dysfunction – Patients with orthostasis or other symptoms suggesting cardiovascular disease or autonomic dysfunction should be referred to a specialist in these areas (see "Mechanisms, causes, and evaluation of orthostatic hypotension" and "Treatment of orthostatic and postprandial hypotension" and "Postural tachycardia syndrome"). Patients suspected of a cardiac structural anomaly should also be referred to an expert in cardiovascular disease.
●Gastrointestinal symptoms – Patients with symptoms of bowel dysmotility or other gastrointestinal disturbance, including rectal prolapse, should be referred to an expert in gastroenterology for evaluation and assistance in management. Irritable bowel syndrome is managed as described separately. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults" and "Treatment of irritable bowel syndrome in adults" and "Overview of rectal procidentia (rectal prolapse)".)
●Genitourinary symptoms – Patients with bladder dysfunction or interstitial cystitis should be referred to an expert in urology or urogynecology. The management of these disorders is described in detail separately. (See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis" and "Evaluation and diagnosis of bladder dysfunction in children" and "Interstitial cystitis/bladder pain syndrome: Management" and "Pelvic organ prolapse in females: Epidemiology, risk factors, clinical manifestations, and management".)
●Symptoms or findings of abnormal hemostasis – Patients with easy bruising or those in whom there is a question of whether a coagulation disorder is also present should be referred to a hematologist with expertise in the evaluation and treatment of bleeding disorders. (See "Approach to the child with bleeding symptoms" and "Approach to the adult with a suspected bleeding disorder".)
●Muscle weakness and/or myalgia – Patients with muscle weakness or pain suspected of a myopathy should be referred to an expert in muscle disease, such as a neurologist or rheumatologist. (See "Approach to the patient with muscle weakness" and "Approach to the patient with myalgia".)
●Symptomatic spinal instability – Patients with symptomatic spinal instability should be evaluated by an expert in the treatment of such disorders, such as a neurosurgeon. The major symptoms indicating a need for consultation are the reproducible exacerbation or precipitation of autonomic and/or neurologic symptoms, such as autonomic dysfunction or pain, when the cervical spine is moved in certain directions [16]. For example, intermittent cervical cord compression can be suggested by symptoms that occur with extension or hyperextension of the cervical spine. The evaluation of such patients may include magnetic resonance imaging (MRI) of the cervical spine and base of the skull with the neck in extension to determine whether cord compression and low-grade Chiari-1 malformations are present. Dynamic upright MRI of the cervical spine with flexion/extension views may reveal significant craniocervical instability responsible for inducing transient dysfunction of the cervical cord and extensive autonomic nervous system dysfunction [16].
PROGNOSIS — The long-term prognoses for patients with hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS; and of joint hypermobility syndrome [JHS] by prior criteria) have not been systematically examined, but several features have been associated with an adverse prognosis in our clinical experience. These include pain, dislocations and recurring injury, chronic fatigue, anxiety and depression, and persistent symptoms of autonomic dysfunction.
A three-year follow-up study of pediatric and adolescent patients identified three subgroups, with the group who deteriorated presenting with higher baseline levels of pain and fatigue and with autonomic symptoms [17]. The strongest predictor of functional decline was the number of multisystemic complaints at baseline (skin, eye, cardiovascular, and genitourinary/gastrointestinal); thus, both an extended phenotype and the presence of autonomic symptoms predicted poor outcomes.
Joint hypermobility does decrease with age in many cases. Also, there have been no longitudinal studies exploring the association between joint hypermobility and possible complications such as early-onset or progressive osteoarthritis.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ehlers-Danlos syndromes and joint hypermobility".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Ehlers-Danlos syndrome (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Treatment should be individualized based upon the patient's symptoms, clinical findings, and response to treatment interventions. Patients should receive education regarding the nature of the condition, and pain management should employ a multidisciplinary approach. (See 'Treatment' above and 'Patient education and self-management' above and 'Musculoskeletal manifestations and pain' above.)
●We suggest that all patients undergo physical therapy rather than providing education or self-management strategies alone (Grade 2C). Whenever available, the physical therapist should have expertise in the care of joint hypermobility and related conditions. The therapist can provide assistance in the management of the musculoskeletal issues, including use of appropriate exercises, splints, and adaptive devices. Patients with significant upper extremity involvement or anatomic abnormalities affecting the feet should be further evaluated and treated by an occupational therapist or podiatrist, respectively. (See 'Musculoskeletal manifestations and pain' above.)
●The management of systemic manifestations associated with hypermobility spectrum disorder (HSD) or hypermobile Ehlers-Danlos syndrome (hEDS) is generally the same or very similar to usual management for these conditions in patients who do not have these diagnoses. Conditions that may require further referral include bowel dysmotility or other gastrointestinal disturbance, orthostasis or other symptoms suggesting cardiovascular disease or autonomic dysfunction, bladder dysfunction or interstitial cystitis, easy bruising or other findings suggesting coagulation disorder, muscle weakness or pain suggestive of a myopathy, and symptomatic spinal instability. (See 'Referral for associated manifestations' above.)
●Most people with joint hypermobility alone, which may affect 10 to 20 percent of the general population to some degree and affect isolated joints or be more generalized, do not experience any problems from the condition; hence, they will not require any treatment. (See 'Approach to management' above.)
