Perspective: Don't Underestimate Joint Hypermobility Syndrome

Once perceived as a predominantly benign condition characterized by joint laxity, hypermobility, and associated musculoskeletal symptoms in otherwise healthy children and adults, joint hypermobility syndrome is now understood to be a multifaceted, multisystemic heritable disorder of connective tissue.

Its range of potential clinical consequences "resonate far beyond the confines of the musculoskeletal system," according to Dr. Rodney Grahame, a consultant rheumatologist at University College Hospital in London. "There is hardly a clinical specialty to be found that is not touched in one way or another by joint hypermobility syndrome" (JHS), he said. In addition to "loose" joints, other symptoms can include pain, joint clicking, joint instability, skin changes, a range of autonomic disturbances, and muscle deconditioning because of pain avoidance.

In this column, Dr. Grahame discusses the clinical manifestations of JHS, widespread misperceptions about the disorder, the consequences of missed or delayed diagnoses, and important diagnostic and treatment considerations.

QUESTION: What are the most important clinical and laboratory features of JHS?

Dr. Grahame: JHS was initially defined in 1967 as the occurrence of musculoskeletal symptoms in the presence of generalized joint hypermobility. Patients usually present with noninflammatory joint and/or spinal pain, recurrent soft tissue injury or overuse lesions, and joint dislocations or subluxations. Over the last decade, it has become evident that chronic pain, dysautonomia, and gastrointestinal dysmotility are frequently encountered complications. In addition to joint hypermobility, key diagnostic features include such skin changes as increased stretchiness, paper-thin scars, striae atrophicae, and features of a marfanoid habitus. There are currently no diagnostic laboratory tests for JHS.

QUESTION: Early literature describes JHS as a mostly harmless condition, but more recent data suggest that the syndrome can have serious clinical consequences. How do these different perspectives affect patient management?

Dr. Grahame: Enormously! In the former view, which is still widely held, hypermobility is largely perceived as a trivial disorder that does not merit serious consideration by rheumatologists on the basis that if there are no inflammatory markers, it is of no consequence. Nothing could be further from the truth. Clinicians appear to be frequently unaware of the recent literature concerning systemic complications, so patients’ complaints may be discounted. Patients may even be told that their symptoms are "in the mind" and that they should see a psychiatrist. They are often left to "shop around" in vain, searching for a doctor who understands and believes their symptoms and attempts to alleviate them (Nat. Clin. Pract. Rheumatol. 2008;4:522-4). By contrast, the identification and recognition of features of a heritable disorder of connective tissue (HDCT) are much more likely to attract serious attention. Unfortunately, the HDCTs are not uniformly taught in rheumatology training programs, and accredited rheumatologists may not be familiar with them. By default, the care of patients with HDCTs may pass to clinical geneticists, who have enormously wide knowledge but who are not trained in rheumatology.

QUESTION: How can clinicians distinguish JHS from other HDCTs, such as Ehlers-Danlos syndrome?

Dr. Grahame: The debate as to whether JHS and Ehlers-Danlos syndrome–hypermobility type (HEDS) are one and the same has raged for 40 years. The tide has now definitely turned in favor of the "lumpers" as against the "splitters". Gradually, as incontrovertibly convincing evidence has appeared, it has become obvious that JHS and HEDS are either truly identical, or if not identical, at least indistinguishable from one another (Am. J. Med. Genet. A. 2009;149A:2368-70).

It is clearly incumbent on all clinicians to be aware of the more serious HDCTs such as Marfan syndrome and Ehlers-Danlos syndrome–vascular type (VEDS), which carry the risk of life-threatening complications, such as aortic aneurysm formation in the case of Marfan’s, and arterial, visceral, or uterine rupture in the case of VEDS. Admittedly, however, it is not always easy to differentiate between those HDCTs that carry such high risk from the more benign JHS/HEDS. Both VEDS and Marfan’s have recognizable phenotypic features and their identification has been facilitated in recent years by genetic testing. One must strive to be alert to the possibility of encountering a more serious form and to be armed with a heightened index of clinical suspicion. Eliciting a careful personal and family history is all-important. This entails seeking out detailed information on close family members, and in particular, those who may have died unexpectedly or suddenly early in life. The advent of the echocardiogram has been a major step forward in spotting early aortic root dilatation at a time when surgical intervention can be lifesaving. Examining the eye by slit-lamp is another useful tool in helping to exclude ocular evidence of Marfan’s.

QUESTION: Is a diagnosis of JHS associated with an increased risk for other musculoskeletal disorders?

Dr. Grahame: Most clinicians are aware of the susceptibility and vulnerability to trauma and joint instability that accompanies hypermobility, but few seem to be cognizant of the devastating effects on function and quality of life posed by the frequent occurrence of chronic pain and deconditioning that can occur if the condition is not handled correctly.

QUESTION: What are some of the consequences of delayed diagnosis, and what are some of the benefits of early diagnosis?

Dr. Grahame: Delayed diagnosis leaves patients not knowing what is causing their pain and distress. Being told that hypermobility cannot be responsible for their degree of pain only serves to cause further dismay. Even more serious than the upset to their emotional equilibrium is the progressive loss of mobility that they suffer, resulting ultimately in their becoming potentially chairbound or even bedbound. Because movement is painful, they intuitively adopt a strategy of pain avoidance through movement avoidance. The result is a predictable decline in independence and a descent into disability. The result is that people who are generally young and formerly physically active in various pursuits can be struck down in their prime, in spite of having locomotor systems that are largely intact.

QUESTION: What are some of the most important management considerations?

Dr. Grahame: Hypermobile subjects should be encouraged to achieve maximal fitness at all ages as a means of avoiding many of the musculoskeletal lesions to which they are predisposed by virtue of their fragile tissues. Having strong muscles helps to improve proprioception, stabilize core muscle groups and unstable joints, and improve stamina. Physical therapists have effectively adapted the principles of physiotherapy to the needs of patients with lax and fragile tissues.

Chronic pain in JHS generally does not respond well to analgesic medications, but pain management using cognitive behavioral methods has enabled many patients to return to a reasonable quality of life. Finally, surgery should be undertaken only after careful consideration of the risks of delayed healing, after the anticipated impact on outcome of a connective tissue disorder have been considered, and when conservative alternative nonsurgical treatments are not available.

This column, "Ask the Expert," regularly appears in Rheumatology News, an Elsevier publication. Dr. Grahame is also an honorary consultant in pediatric rheumatology at the Great Ormond Street Hospital for Children and emeritus professor of rheumatology at University College London. He disclosed having no conflicts of interest.

Once perceived as a predominantly benign condition characterized by joint laxity, hypermobility, and associated musculoskeletal symptoms in otherwise healthy children and adults, joint hypermobility syndrome is now understood to be a multifaceted, multisystemic heritable disorder of connective tissue.

Its range of potential clinical consequences "resonate far beyond the confines of the musculoskeletal system," according to Dr. Rodney Grahame, a consultant rheumatologist at University College Hospital in London. "There is hardly a clinical specialty to be found that is not touched in one way or another by joint hypermobility syndrome" (JHS), he said. In addition to "loose" joints, other symptoms can include pain, joint clicking, joint instability, skin changes, a range of autonomic disturbances, and muscle deconditioning because of pain avoidance.

In this column, Dr. Grahame discusses the clinical manifestations of JHS, widespread misperceptions about the disorder, the consequences of missed or delayed diagnoses, and important diagnostic and treatment considerations.

QUESTION: What are the most important clinical and laboratory features of JHS?

Dr. Grahame: JHS was initially defined in 1967 as the occurrence of musculoskeletal symptoms in the presence of generalized joint hypermobility. Patients usually present with noninflammatory joint and/or spinal pain, recurrent soft tissue injury or overuse lesions, and joint dislocations or subluxations. Over the last decade, it has become evident that chronic pain, dysautonomia, and gastrointestinal dysmotility are frequently encountered complications. In addition to joint hypermobility, key diagnostic features include such skin changes as increased stretchiness, paper-thin scars, striae atrophicae, and features of a marfanoid habitus. There are currently no diagnostic laboratory tests for JHS.

QUESTION: Early literature describes JHS as a mostly harmless condition, but more recent data suggest that the syndrome can have serious clinical consequences. How do these different perspectives affect patient management?

Dr. Grahame: Enormously! In the former view, which is still widely held, hypermobility is largely perceived as a trivial disorder that does not merit serious consideration by rheumatologists on the basis that if there are no inflammatory markers, it is of no consequence. Nothing could be further from the truth. Clinicians appear to be frequently unaware of the recent literature concerning systemic complications, so patients’ complaints may be discounted. Patients may even be told that their symptoms are "in the mind" and that they should see a psychiatrist. They are often left to "shop around" in vain, searching for a doctor who understands and believes their symptoms and attempts to alleviate them (Nat. Clin. Pract. Rheumatol. 2008;4:522-4). By contrast, the identification and recognition of features of a heritable disorder of connective tissue (HDCT) are much more likely to attract serious attention. Unfortunately, the HDCTs are not uniformly taught in rheumatology training programs, and accredited rheumatologists may not be familiar with them. By default, the care of patients with HDCTs may pass to clinical geneticists, who have enormously wide knowledge but who are not trained in rheumatology.

QUESTION: How can clinicians distinguish JHS from other HDCTs, such as Ehlers-Danlos syndrome?

Dr. Grahame: The debate as to whether JHS and Ehlers-Danlos syndrome–hypermobility type (HEDS) are one and the same has raged for 40 years. The tide has now definitely turned in favor of the "lumpers" as against the "splitters". Gradually, as incontrovertibly convincing evidence has appeared, it has become obvious that JHS and HEDS are either truly identical, or if not identical, at least indistinguishable from one another (Am. J. Med. Genet. A. 2009;149A:2368-70).

It is clearly incumbent on all clinicians to be aware of the more serious HDCTs such as Marfan syndrome and Ehlers-Danlos syndrome–vascular type (VEDS), which carry the risk of life-threatening complications, such as aortic aneurysm formation in the case of Marfan’s, and arterial, visceral, or uterine rupture in the case of VEDS. Admittedly, however, it is not always easy to differentiate between those HDCTs that carry such high risk from the more benign JHS/HEDS. Both VEDS and Marfan’s have recognizable phenotypic features and their identification has been facilitated in recent years by genetic testing. One must strive to be alert to the possibility of encountering a more serious form and to be armed with a heightened index of clinical suspicion. Eliciting a careful personal and family history is all-important. This entails seeking out detailed information on close family members, and in particular, those who may have died unexpectedly or suddenly early in life. The advent of the echocardiogram has been a major step forward in spotting early aortic root dilatation at a time when surgical intervention can be lifesaving. Examining the eye by slit-lamp is another useful tool in helping to exclude ocular evidence of Marfan’s.

QUESTION: Is a diagnosis of JHS associated with an increased risk for other musculoskeletal disorders?

Dr. Grahame: Most clinicians are aware of the susceptibility and vulnerability to trauma and joint instability that accompanies hypermobility, but few seem to be cognizant of the devastating effects on function and quality of life posed by the frequent occurrence of chronic pain and deconditioning that can occur if the condition is not handled correctly.

QUESTION: What are some of the consequences of delayed diagnosis, and what are some of the benefits of early diagnosis?

Dr. Grahame: Delayed diagnosis leaves patients not knowing what is causing their pain and distress. Being told that hypermobility cannot be responsible for their degree of pain only serves to cause further dismay. Even more serious than the upset to their emotional equilibrium is the progressive loss of mobility that they suffer, resulting ultimately in their becoming potentially chairbound or even bedbound. Because movement is painful, they intuitively adopt a strategy of pain avoidance through movement avoidance. The result is a predictable decline in independence and a descent into disability. The result is that people who are generally young and formerly physically active in various pursuits can be struck down in their prime, in spite of having locomotor systems that are largely intact.

QUESTION: What are some of the most important management considerations?

Dr. Grahame: Hypermobile subjects should be encouraged to achieve maximal fitness at all ages as a means of avoiding many of the musculoskeletal lesions to which they are predisposed by virtue of their fragile tissues. Having strong muscles helps to improve proprioception, stabilize core muscle groups and unstable joints, and improve stamina. Physical therapists have effectively adapted the principles of physiotherapy to the needs of patients with lax and fragile tissues.

Chronic pain in JHS generally does not respond well to analgesic medications, but pain management using cognitive behavioral methods has enabled many patients to return to a reasonable quality of life. Finally, surgery should be undertaken only after careful consideration of the risks of delayed healing, after the anticipated impact on outcome of a connective tissue disorder have been considered, and when conservative alternative nonsurgical treatments are not available.

This column, "Ask the Expert," regularly appears in Rheumatology News, an Elsevier publication. Dr. Grahame is also an honorary consultant in pediatric rheumatology at the Great Ormond Street Hospital for Children and emeritus professor of rheumatology at University College London. He disclosed having no conflicts of interest.

Once perceived as a predominantly benign condition characterized by joint laxity, hypermobility, and associated musculoskeletal symptoms in otherwise healthy children and adults, joint hypermobility syndrome is now understood to be a multifaceted, multisystemic heritable disorder of connective tissue.

Its range of potential clinical consequences "resonate far beyond the confines of the musculoskeletal system," according to Dr. Rodney Grahame, a consultant rheumatologist at University College Hospital in London. "There is hardly a clinical specialty to be found that is not touched in one way or another by joint hypermobility syndrome" (JHS), he said. In addition to "loose" joints, other symptoms can include pain, joint clicking, joint instability, skin changes, a range of autonomic disturbances, and muscle deconditioning because of pain avoidance.

In this column, Dr. Grahame discusses the clinical manifestations of JHS, widespread misperceptions about the disorder, the consequences of missed or delayed diagnoses, and important diagnostic and treatment considerations.

QUESTION: What are the most important clinical and laboratory features of JHS?

Dr. Grahame: JHS was initially defined in 1967 as the occurrence of musculoskeletal symptoms in the presence of generalized joint hypermobility. Patients usually present with noninflammatory joint and/or spinal pain, recurrent soft tissue injury or overuse lesions, and joint dislocations or subluxations. Over the last decade, it has become evident that chronic pain, dysautonomia, and gastrointestinal dysmotility are frequently encountered complications. In addition to joint hypermobility, key diagnostic features include such skin changes as increased stretchiness, paper-thin scars, striae atrophicae, and features of a marfanoid habitus. There are currently no diagnostic laboratory tests for JHS.

QUESTION: Early literature describes JHS as a mostly harmless condition, but more recent data suggest that the syndrome can have serious clinical consequences. How do these different perspectives affect patient management?

Dr. Grahame: Enormously! In the former view, which is still widely held, hypermobility is largely perceived as a trivial disorder that does not merit serious consideration by rheumatologists on the basis that if there are no inflammatory markers, it is of no consequence. Nothing could be further from the truth. Clinicians appear to be frequently unaware of the recent literature concerning systemic complications, so patients’ complaints may be discounted. Patients may even be told that their symptoms are "in the mind" and that they should see a psychiatrist. They are often left to "shop around" in vain, searching for a doctor who understands and believes their symptoms and attempts to alleviate them (Nat. Clin. Pract. Rheumatol. 2008;4:522-4). By contrast, the identification and recognition of features of a heritable disorder of connective tissue (HDCT) are much more likely to attract serious attention. Unfortunately, the HDCTs are not uniformly taught in rheumatology training programs, and accredited rheumatologists may not be familiar with them. By default, the care of patients with HDCTs may pass to clinical geneticists, who have enormously wide knowledge but who are not trained in rheumatology.

QUESTION: How can clinicians distinguish JHS from other HDCTs, such as Ehlers-Danlos syndrome?

Dr. Grahame: The debate as to whether JHS and Ehlers-Danlos syndrome–hypermobility type (HEDS) are one and the same has raged for 40 years. The tide has now definitely turned in favor of the "lumpers" as against the "splitters". Gradually, as incontrovertibly convincing evidence has appeared, it has become obvious that JHS and HEDS are either truly identical, or if not identical, at least indistinguishable from one another (Am. J. Med. Genet. A. 2009;149A:2368-70).

It is clearly incumbent on all clinicians to be aware of the more serious HDCTs such as Marfan syndrome and Ehlers-Danlos syndrome–vascular type (VEDS), which carry the risk of life-threatening complications, such as aortic aneurysm formation in the case of Marfan’s, and arterial, visceral, or uterine rupture in the case of VEDS. Admittedly, however, it is not always easy to differentiate between those HDCTs that carry such high risk from the more benign JHS/HEDS. Both VEDS and Marfan’s have recognizable phenotypic features and their identification has been facilitated in recent years by genetic testing. One must strive to be alert to the possibility of encountering a more serious form and to be armed with a heightened index of clinical suspicion. Eliciting a careful personal and family history is all-important. This entails seeking out detailed information on close family members, and in particular, those who may have died unexpectedly or suddenly early in life. The advent of the echocardiogram has been a major step forward in spotting early aortic root dilatation at a time when surgical intervention can be lifesaving. Examining the eye by slit-lamp is another useful tool in helping to exclude ocular evidence of Marfan’s.

QUESTION: Is a diagnosis of JHS associated with an increased risk for other musculoskeletal disorders?

Dr. Grahame: Most clinicians are aware of the susceptibility and vulnerability to trauma and joint instability that accompanies hypermobility, but few seem to be cognizant of the devastating effects on function and quality of life posed by the frequent occurrence of chronic pain and deconditioning that can occur if the condition is not handled correctly.

QUESTION: What are some of the consequences of delayed diagnosis, and what are some of the benefits of early diagnosis?

Dr. Grahame: Delayed diagnosis leaves patients not knowing what is causing their pain and distress. Being told that hypermobility cannot be responsible for their degree of pain only serves to cause further dismay. Even more serious than the upset to their emotional equilibrium is the progressive loss of mobility that they suffer, resulting ultimately in their becoming potentially chairbound or even bedbound. Because movement is painful, they intuitively adopt a strategy of pain avoidance through movement avoidance. The result is a predictable decline in independence and a descent into disability. The result is that people who are generally young and formerly physically active in various pursuits can be struck down in their prime, in spite of having locomotor systems that are largely intact.

QUESTION: What are some of the most important management considerations?

Dr. Grahame: Hypermobile subjects should be encouraged to achieve maximal fitness at all ages as a means of avoiding many of the musculoskeletal lesions to which they are predisposed by virtue of their fragile tissues. Having strong muscles helps to improve proprioception, stabilize core muscle groups and unstable joints, and improve stamina. Physical therapists have effectively adapted the principles of physiotherapy to the needs of patients with lax and fragile tissues.

Chronic pain in JHS generally does not respond well to analgesic medications, but pain management using cognitive behavioral methods has enabled many patients to return to a reasonable quality of life. Finally, surgery should be undertaken only after careful consideration of the risks of delayed healing, after the anticipated impact on outcome of a connective tissue disorder have been considered, and when conservative alternative nonsurgical treatments are not available.

This column, "Ask the Expert," regularly appears in Rheumatology News, an Elsevier publication. Dr. Grahame is also an honorary consultant in pediatric rheumatology at the Great Ormond Street Hospital for Children and emeritus professor of rheumatology at University College London. He disclosed having no conflicts of interest.