EDS – A RHEUMATOLOGIST’S PERSPECTIVE OVER FOUR DECADES

1. EDS – A RHEUMATOLOGIST’S PERSPECTIVE OVER FOUR DECADES RODNEY GRAHAME CONSULTANT RHEUMATOLOGIST UNIVERSITY COLLEGE HOSPITAL LONDON HONORARY PROFESOR UNIVERSITY COLLEGE LONDON AFFILIATE PROFESSOR , UNIVERSITY OF WASHINGTON

2. “THE HYPERMOBILITY SYNDROME” “Musculoskeletal symptoms in the presence of generalised joint laxity in otherwise normal subjects”.

3. “THE HYPERMOBILITY SYNDROME” “Another view is that isolated ligamentous laxity is a mild mesenchymal developmental disorder which lies at one end of a spectrum of heredo-familial connective tissue disease with the fully-developed picture of MFS or EDS at the other [Brown, Rowatt & Rose 1966].

5. QUESTIONS TO BE ADDRESSED • WHAT DO RHEUMATOLOGISTS REALLY THINK ABOUT HYPERMOBILITY SYNDROME? • HOW COMMON IS HYPERMOBILITY SYNDROME? • HOW OFTEN IS IT MISSED? • WHY IS IT SO FREQUENTLY MISSED? • WHAT IS THE IMPACT OF MISSING THE DIAGNOSIS? • WHAT TREATMENT HAS BEEN SHOWN TO HELP?

6. (1) WHAT DO RHEUMATOLOGISTS REALLY THINK ABOUT HMS?

7. BSR MEMBERS’ HYPERMOBILITY SYNDROME PERCEPTION SURVEY 1999 [Grahame R, Bird H. Rheumatology 40 (5):559 -62 , 2001] QUESIONNAIRES ISSUED 420 RETURNED 315 RESPONSE RATE 75%

8. Do you believe in HMS as a distinct clinical entity?

9. Do you believe in HMS as a distinct pathological entity?

10. Do you regard the presence of a +ve family history as necessary for a diagnosis of HMS?

11. Do you regard the presence of extraarticular features as necessary for a diagnosis of HMS?

12. In your opinion are HMS and Ehlers-Danlos type 3 (EDS III)?

13. How do you rate the impact of HMS on peoples’ lives in most cases?

14. What contribution does HMS make to the overall burden of rheumatic disease morbidity?

15. What contribution does HMS make to the overall burden of rheumatic disease morbidity?

16. (2) HOW COMMON IS HMS?

19. Beighton score > 4/9 or (currently/historically) Arthralgia > 3 months in >4 joints Beighton score of 1,2, 3/9 (0, if aged 50+) Arthralgia in 1-3 joints/ back pain/spondylosis/ spondylolysis/’olisthesis. Dislocation in >1 joint, or in 1 joint on >1 x > 3 soft tissue lesions Marfanoid habitus Skin: striae, thin, stretchy, abnormal scarring. Eye signs: drooping eyelids or myopia Varicose veins/hernia/ uterine/rectal prolapse Revised “1998 Brighton” diagnostic criteria forthe Benign Joint Hypermobility Syndrome MAJOR CRITERIAMINOR CRITERIA The BJHS is diagnosed with: 2 major criteria or 1major and 2 minor criteria or 4minor criteria. 2 minor + 1° degree relative. BJHS is excluded by presence of Marfan or Ehlers-Danlos syndromes (other than the EDS Hypermobility type formerly EDS III) as defined by the Ghent 1996 and Villefranche 1998 criteria respectively

20. Willesden Community Hospital 506 unselected consecutive new referrals rheumatology clinic June 2003 – February 2005 grouped by gender presence / absence of JHS (JHS+ / JHS-) [BRIGHTON] primary diagnosis race (Caucasian / non-Caucasian (Cauc+ / Cauc-)).

21. AIMS OF THE STUDY TO DETERMINE THE CLINIC PREVALENCE OF THE JHS/EDS PHENOTYPE IN A N. LONDON HOSPITAL BY APPLYING THE BRIGHTON CRITERIA TO INVESTIGATE THE INFLUENCE OF: GENDER ETHNIC BACKGROUND PRESENCE/ABSENCE OF THE JHS/EDS PHENOTYPE ON THE CLINICAL PRESENTATION

22. INFLUENCE OF GENDER AND ETHNIC BACKGROUND ON CLINIC PREVALENCE OF JHS PHENOTYPE NON-CAUCASIAN FEMALES [183] NON-CAUCASIAN MALES [94] CAUCASIAN FEMALES [140] CAUCASIAN MALES [89]

23. PRESENTING LESION BY JHS/EDS STATUS – NON-CAUCASIAN FEMALES [69]

24. PRESENTING LESION BY JHS/EDS STATUS+ NON-CAUCASIAN FEMALES [114]

25. PRESENCE OF JHS/EDS PHENOTYPE IS ASSOCIATED WITH: IN CAUCASIAN FEMALES: • MORE JT PAIN (x3); MORE SPINAL PAIN (x2) • LESS INFLAM JT DIS (x1/4); SOFT TISSUE (x1/2) IN CAUCASIAN MALES: • MORE JT PAIN (x3); MORE SPINAL PAIN (x2) • LESS OA (x1/2); NO INFLAM JT DIS!

26. CONCLUSIONS (1) • JHS IS A COMMON, LARGELY UNRECOGNISED HDCT • 1ST STUDY OF CLINIC PREVALENCE OF JHS IN UNSELECTED RHEUMATOLOGY OUTPATIENTS • UNEXPECTEDLY HIGH PREVALENCE OF JHS • PREVALENCE STRONGLY INFLUENCED BY GENDER AND ETHNICITY.

27. CONCLUSIONS (2) • PRESENTING COMPLAINTS ARE STRONGLY INFLUENCED BY: • GENDER • ETHNIC ORIGIN • PRESENCE OF JHS PHENOTYPE

28. CONCLUSIONS (2) • PRESENTING COMPLAINTS ARE STRONGLY INFLUENCED BY: • GENDER • ETHNIC ORIGIN • PRESENCE OF JHS PHENOTYPE

29. JHS PHENOTYPE IS ASSOCIATED WITH: • MORE NON-INFLAMMATORY JOINT PAIN • MORE NON-INFLAMMATORY SPINAL PAIN • MUCH LESS INFLAMMATORY JOINT DISEASE • LESS OA • MORE WIDESPREAD CHRONIC PAIN (female/non-Caucasian only)

30. QUESTIONS • DOES THIS STUDY ESTABLISH JHS AS THE MOST COMMON RHEUMATIC DISORDER? • DOES JHS PROTECT AGAINST INFLAMMATORY JOINT DISEASE? • SHOULD THE BRIGHTON CRITERIA BE ROUTINELY APPLIED TO ALL PATIENTS WITH MSK Sx?

31. (3) HOW OFTEN IS HMS MISSED?

33. The prevalence of the JHS in clinical practice is unknown. • But how common is JHS? • How often does it appear in rheumatology clinics? • How often is the diagnosis being missed? • What diagnostic labels are being applied to these patients? • Does it matter?

34. EXTRAPOLATIONS • In 2002/3 there were 266,264 1st hospital OP rheumatology attendances in England. • If 41% have JHS/EDSHM phenotype • There are 109,168 NEW JHS patients attending clinics annually! • There are 536 consultants in England! • Each consultant is seeing 224 JHS ptsp.a! • This is equivalent to 4 per week!

35. Approx how many HMS cases have you seen in the past year?

36. ESTIMATES OF MISSED CASES • Each consultant is actually seeing 224 JHS pts/yr • Estimated 119,809 NEW JHS patients attending clinics annually • Consultants estimate 5,600 NEW JHS patients attending their clinics annually [10 EACH] • 119,809 JHS patients unrecognised p.a. • Equivalent to 94.52%! • Only 4.67% are being recognised!

37. ESTIMATES OF MISSED CASES • “for every single patient in England with joint hypermobility syndrome fortunate enough to be correctly diagnosed by a rheumatologist, there are 19 others who are not, passing unnoticed, undiagnosed and presumably, untreated!”

38. POPULATION STATISTICS • England 49 million • USA 311 million

39. ESTIMATES OF NEW CASES MISSED ANNUALLY! • England 103,568 • USA 657,340

40. (4) WHY IS IT SO FREQUENTLY MISSED?

41. WHY IS IT SO FREQUENTLY MISSEDBY RHEUMATOLOGISTS?

42. LACK OF AWARENESS IN JHS OF: • PHENOTYPIC FEATURES • IMPACT ON PEOPLES’ LIVES • UNFAVOURABLE PROGNOSIS IF UNTREATED • SEEN AS A PURELY JOINT (NOT A CONNECTIVE TISSUE) DISORDER • IN ‘NORMAL’ PEOPLE (LEGACY OF 1967!). • NOT SURPRISING THAT IT IS MOSTLY MISDIAGNOSED AS: • FIBROMYALGIA • CFS • SOMATISATION etc.

43. UNWILLINGNESS TO COMMIT TO A PRECISE GENETIC DIAGNOSIS • ‘HYPERMOBILITY IS NOT A DIAGNOSIS!’ • H/M OBSERVED, BUT THEN DISREGARDED! • EXCESSIVE FOCUS HAS BEEN ON FIBROMALGIA! • NOT FAMILIAR WITH RECENT LITERATURE! • UNEASY WITH DIAGNOSIS OF EDS! • FAULT IN TRAINING & CONTINUING MEDICAL EDUCATION?

44. Unique in the annals of medicine! • High prevalence! • Familial aggregation. • Clinically easily recognised if sought! • Affects all ages from the cradle to the grave! • No costly imaging or genetic testing! • Principles of management have been laid down • Major cause of preventable disability and psychological distress!

45. Unique in the annals of medicine! • BUT: • Medical students generally not taught about it! • Teachers of medical students don’t teach it. • Doctors in general tend not to know about it! • Rheumatologists still follow concepts of 1970s! • Most therapists are at a loss as to how to treat it! • Epidemiologists have chosen to ignore it! • Research Funding bodies rarely support it! • Social Welfare does not recognise it! • Patients are left to their own devices! • No other disease is mis-treated in this way!

46. WHAT IS THE IMPACT OF MISSING THE DIAGNOSIS?

47. SEVERELY PHYSICALLY DISABLED MSK SYSTEM LARGELY INTACT! CHRONIC PAIN – ‘KINESIPHOBIA’ MEDICAL: AUTONOMIC; GI; GYNAE etc. MOSTLY YOUNG, HIGHLY MOTIVATED CUT DOWN IN THEIR PRIME OFTEN TOLD THAT IT IS ‘ALL IN THE MIND’ FEEL DISPIRITED, ABANDONED, ANGRY NO NATIONAL CENTRE FOR CARE! The New Rheumatological Disability!

48. WHAT TREATMENT HAS BEEN SHOWN TO HELP?

49. The Aims of Rehabilitation(After Anna Edwards-Fowler and Rosemary Keer) • education reassurance, and advice • improving spinal posture by developing core stability • enhancing joint stability by encouraging joint-stabilising exercises • improving joint proprioception by suitable exercises • avoiding resting in end-of-range (harmful) postures • manual therapy to restore normal (hyper) mobility • using pacing, coping and other behavioural strategies in severe or widespread chronic pain. • reversing deconditioning and enhancing fitness and stamina by aerobic exercise • invoking self-management thereby restoring self-esteem and self-efficacy.