Non-musculoskeletal symptoms in joint hypermobility syndrome. Indirect evidence for autonomic dysfunction?

A. J. Hakim1,2 and R. Grahame1

1 Centre for Rheumatology, University College London Hospitals and 2 Academic Rheumatology and Osteoporosis Unit, Whipps Cross University Hospital, London, UK

Correspondence to: A. J. Hakim, Whipps Cross University Hospital, Leytonstone, London E11 1NR, UK. E-mail: alanhakim{at}aol.com

SIR, Joint hypermobility syndrome (JHS) is a chronically disabling disorder manifested as widespread pain, fatigue, multiple soft tissue lesions and fragility of skin and supportive connective tissues [1]. It is a condition that is often overlooked by clinicians [2]. Moreover, clinical experience suggests that previously unrecognized non-musculoskeletal symptoms, including presyncope, palpitations and bowel disturbance, are also common in JHS. Recent evidence demonstrates dysfunction of the autonomic nervous system as an explanation for these symptoms [3]. Recognition of these symptoms by clinicians is an important part of patient assessment and education, even if the pathophysiology remains unclear.

We have examined the prevalence of non-musculoskeletal complaints and explored their associations to determine whether they reflect a tendency to report multiple, non-specific concerns.

One hundred and seventy women aged between 18 and 65 yr were seen in a teaching hospital hypermobility clinic over a 2-yr period. Each was diagnosed with JHS using the 1998 Brighton criteria [4]. Individuals completed a self-reported questionnaire enquiring about symptoms experienced on a ‘regular basis’. The questionnaire was structured so that patients were unaware of any hypothesis. Fifty female hospital staff acted as controls, having been identified as non-hypermobile by the use of a five-part self-report questionnaire [5]. The symptoms explored clustered into five domains: (i) (pre)syncope (feel faint, actually faint, dizziness and light-headedness); (ii) cardiorespiratory (CR) (palpitations, chest pain and shortness of breath); (iii) gastrointestinal (GI) (nausea, stomach ache, diarrhoea and constipation); (iv) common JHS concerns (fatigue, joint pain, anxiety and depression); and (v) non-specific (migraine, allergy, rash, nocturia, dysuria, flushing, night sweats, fever, lymph gland pain and poor sleep).

Similar symptoms were combined for analysis. For example, dizziness and light-headedness were considered synonymous with presyncope and were not treated as mutually exclusive. They were combined, so that a person giving both in their response was only counted once within the domain.

We found that 41, 26 and 37% of individuals with JHS reported at least one symptom suggestive of a (pre)syncopal, CR or GI complaint respectively. This compared with 15, 12 and 16% of controls, despite controls being older by a mean of 13 yr [32 yr (range 18–65) vs 45 yr (range 23–64)].

Pain, fatigue, anxiety and depression were, as one would expect, more common in JHS patients (91, 71, 32 and 38% respectively) than controls (30, 30, 12 and 8% respectively). Migraine, rashes and poor sleep were also over-represented amongst JHS patients. Other non-specific complaints (allergy, nocturia, dysuria, flushing, night sweats, fever and lymph gland pain) were equally distributed in cases and controls (Fig. 1).



View larger version (45K):
[in this window]
[in a new window]
 
FIG. 1. Bar chart showing the percentage proportions of patients and controls reporting symptoms.

 
Analysis was extended to look just at JHS patients, comparing those reporting (pre)syncopal, CR or GI concerns (or any combination of the three domains) against those who did not. Sixty per cent of patients recorded at least one type of concern relating to (pre)syncopal, CR or GI symptoms. Of this 60%, 28% reported concerns in one domain, 20% concerns within two domains, and 12% in all three. Those JHS patients classified as having symptoms in two or more of the three domains were found to account for 90% of all JHS patients reporting flushing or night sweats. Moreover, this group were three times more likely to complain of fatigue and anxiety [odds ratio 2.8 (95% confidence interval 1.3–6.3), P = 0.01] than their peers, fatigue and anxiety also being found to be independently associated with migraine and poor sleep (odds ratio 2.6 and 3.5 respectively). Age was not a confounder. No association was found with the other non-specific complaints (Fig. 2).



View larger version (49K):
[in this window]
[in a new window]
 
FIG. 2. Bar chart showing percentage proportions of symptom reporting in JHS patients only, classified by the presence or absence of at least two autonomic symptom domains.

 
We conclude that non-musculoskeletal symptoms are common in patients with JHS and that individuals with these symptoms may express more fatigue, anxiety, migraine, flushing, night sweats and poor sleep than their peers. The pathophysiological basis for these symptoms needs to be explored further but may be a complication of autonomic dysfunction. Alternative explanations might include the side-effect of medications, particularly analgesics and antidepressants, or the presence of comorbidity. In our experience, however, the majority of patients seeing us for the first time are no longer taking such medications as they have often been of little benefit. We note also that very few patients have specific cardiovascular, respiratory or bowel disease.

Potential manifestations of autonomic pathology include cardiac dysrhythmias, postural orthostatic tachycardia syndrome, orthostatic hypotension and orthostatic intolerance. Mechanisms leading to such phenomena in JHS patients may include weakened vascular tissue elasticity and impaired peripheral vasoregulation as a consequence of adrenoceptor or neuronal abnormalities. Similar symptoms are found in chronic fatigue syndrome [6]. Consequently, these disturbances might also be secondary and reflect a degree of physical deconditioning rather than a primary autonomic or connective tissue pathology. Further studies are required. In the meantime, clinical assessment should include an enquiry as to the presence of such symptoms, and health professionals should acknowledge that they are often encountered among patients with JHS.

Ethical approval for the use of a general questionnaire identifying features of JHS both in clinical and epidemiological studies was gained from Guy's Hospital, London. Verbal consent was deemed sufficient.

The authors have declared no conflicts of interest.

References

  1. Hakim AJ, Grahame R. Joint hypermobility. Best Pract Res Clin Rheumatol 2003;17:989–1004.[CrossRef][ISI][Medline]
  2. Grahame R, Bird H. British consultant rheumatologists’ perceptions about the hypermobility syndrome: a national survey. Rheumatology 2001;40:559–62.[Abstract/Free Full Text]
  3. Gazit Y, Nahir AM, Grahame R, Jacob G. Dysautonomia in the hypermobility syndrome. Am J Med 2003;115:33–40.[CrossRef][ISI][Medline]
  4. Grahame R, Bird HA, Child A. The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS). J Rheumatol 2000;27:1777–9.[ISI][Medline]
  5. Hakim AJ, Grahame R. A simple questionnaire to detect hypermobility: an adjunct to the assessment of patients with diffuse musculoskeletal pain. Int J Clin Pract 2003;57:163–6.[ISI][Medline]
  6. Gerrity TR, Bates J, Bell DS et al. Chronic fatigue syndrome: what role does the autonomic nervous system play in the pathophysiology of this complex illness? Neuroimmunomodulation 2002;10:134–41.[CrossRef][ISI][Medline]
Accepted 19 May 2004





This Article
Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Hakim, A. J.
Articles by Grahame, R.
PubMed
PubMed Citation
Articles by Hakim, A. J.
Articles by Grahame, R.