Ehlers Danlos Syndrome: Recognition, Diagnosis & Management

1. Ehlers Danlos Syndrome: Recognition, Diagnosis & Management Howard P. Levy, M.D., Ph.D. Assistant Professor, Johns Hopkins University Johns Hopkins Adolescent Medicine Grand Rounds Baltimore, MD October 12, 2012

2. Disclosures • No relevant financial relationships • I will discuss non-FDA labeled use of the following medications: • Tricyclic antidepressants for neuropathic pain • SNRI antidepressants for neuropathic pain • Anti-seizure medications for neuropathic pain

3. Learning Objectives • Recognize features of EDS • Initiate appropriate evaluation • Understand activity and other management recommendations

4. Case 1: 18 yo Girl With Knee Pain & Instability • 5-6 yrs bilat knee pain & patellar instability • Failed: • steroid & Synvisc injections • debridement, chondroplasties, plication, synovectomy, lateral release, osteotomies, ligament reconstruction (11 total procedures) • aquatic resistance exercise • Gave up lacrosse, soccer, horse riding • Easy bruising, no other skin sx’s

5. Case 1: Exam • Palate: normal • Tender paralumbar spasm • Laxity in all joints • Pesplanus • Beighton score 8/9 • Skin normal

6. Case 2: 32 yo Man With Left Shoulder Pain • Acute onset weightlifting 1 year prior • Improves w/rest; recurs w/weightlifting • Also pain in forearms & knees • No subluxations/dislocations • Failed resistance bands & light weights • Easy bruising, prolonged bleeding • Fatigue on/off x 15 years

7. Case 2: Exam • Palate: high, narrow, intact • Tender left trapezius spasm • Laxity • Shoulders, elbows, wrists, fingers • Left knee only (muscular, especially LE) • Pesplanus • Beighton score 8/9 • Skin normal

8. Case 3: 15 yo Girl With Shoulder Pain & Instability • 10 months of • pain w/push ups • subluxation w/swimming • Hip subluxation (spont vs. traumatic?) • Gave up volleyball • Continues to tolerate swimming, cross-country, and track

9. Case 3: Exam • Palate: normal • Tender paralumbar spasm • Laxity • moderate in shoulders; mild in wrists/fingers • none elsewhere • Beighton score 2/9 (thumbs only) • Skin normal

10. Diagnoses • Case 1: Ehlers DanlosHypermobility Type • Case 2: Ehlers DanlosHypermobility Type • Case 3: Isolated shoulder pain/instability

11. Ehlers Danlos Syndrome HYPERMOBILITY TYPE (III) • Joint laxity • Pain (arthralgia, myalgia, headache) • Fatigue • Worse with resistance & activity • High narrow palate/dental crowding • Easy bruising, mildly soft skin

12. Heritable disorders of connective tissue Collagen Prevalence 1:5000? (probably more common) Ehlers Danlos Syndromes

13. Ehlers Danlos Syndromes • Joint laxity • Soft skin • Easy bruisability • High narrow palate • Gastritis & IBS • POTS & NMH

14. EDS Types

15. EDS: Revised NosologyBeighton et al, Am J Med Genet (1998) 77:31-37

16. “Benign Joint Hypermobility Syndrome”1 Joint laxity Soft skin Easy bruisability Least severe, BUTpaindisability Autosomal dominant Genetic cause unknown 1. Tinkle et al. Am J Med Genet A. 2009;149A:2368–70 EDS: Hypermobility (III)

17. Subjective ROM Hyperextension Lateral instability A/P instability Varus/valgus Telescoping Objective Beighton Scale1 9 possible points “+” = 5 or more Doesn’t assess all joints Not “Gold Std” Assessing Joint Laxity 1. Beightonet al. Ann Rheum Dis. 1973;32:413–8

18. Beighton Scale Palms to floor, knees straight: 1 point

19. Lateral Humeral Epicondyle Radial Styloid Humeral Head Beighton Scale Hyperextend elbow >10o: 1 point each

20. Greater Trochanter Lateral Femoral Condyle Lateral Malleolus Beighton Scale Hyperextend knee >10o: 1 point each

21. Appose thumb to forearm: 1 point each Beighton Scale Dorsiflex 5th finger >90o: 1 point each

22. Assessing Joint Laxity Caveats • Age • Young children: loose • Older adults: stiff • Sex: Female looser than male • Trauma/DJD/Surgery • Muscle tone or bulk • Guarding

23. EDS: Classical (I & II) • All features of Hypermobility Type • More severe skin and soft tissue • Autosomal Dominant • Type 5 collagen in 50% of pts • 90-95% w/stricter clinical criteria1 • Clinical DNA test available • clinical utility? 1. Symoenset al. Hum Mutat. 2012; 33:1485–1493

24. EDS: Classical -Skin • Very soft, sometimes doughy • Hyperelasticity • Avoid loose skin • Volar wrist— normal ~1 cm

25. EDS: Classical -Skin • Very soft, sometimes doughy • Hyperelasticity • Skin fragility • Extensor surfaces

26. EDS: Classical -Skin • Molluscoid pseudotumor • Thickened • Hyperpigmented • Elbows • Knees Atrophic Scars

27. EDS: Classical –Soft Tissue • Wound dehiscence • Soft tissue fragility (“wet toilet paper”) • Ligaments & Tendons • Rarely vascular tears

28. EDS: Vascular (IV) • Joint laxity • Small >> large • Wrists, fingers, ankles, toes

29. EDS: Vascular (IV) • Joint laxity • Fragile skin • Thin translucent skin

30. EDS: Vascular (IV) • Wound dehiscence • Dissection/rupture • Arteries • Intestine • Uterus • Tendons • Some never dissect/rupture • 80% of 1st events ages 10-39

31. EDS: Vascular (IV) • Autosomal Dominant • Type 3 Collagen (100% of pts.) • Skin, vessels, hollow organs • Clinical DNA sequencing • Biochemical assay from skin fibroblasts also available

32. Differential Dx: Joint Laxity WWW.OMIM.ORG

33. Differential Dx: Joint Laxity Dozens other than EDS • Marfan • Loeys-Dietz • Stickler • Fragile X • Turner

34. Diagnostic Work-up • Joint & skin exam • Echo (diff dx & clinical mgmt) • Aortic root dilation (up to 1/3 patients) • Other abnormalities • Ophtho if suspect Marfan or Stickler • Genetics consultation

35. Management

36. What We Know • Laxity & instability • Pain—out of proportion to exam/x-rays • Fatigue • Osteoarthritis (DJD)

37. What We Don’t Know Why?

38. Working Hypothesis Laxity Frequent minor subluxations Reflexive muscle spasm Osteoarthritis Pain Fatigue

39. Working Hypothesis Laxity Frequent minor subluxations Reflexive muscle spasm Osteoarthritis Pain Fatigue

40. Joint Instability MUSCLE TONING Strength: A source of power or force Tone: The normal state of elastic tension or partial contraction in resting muscles Increased strength can sublux the joints Increased tone can improve joint stability

41. Avoid (minimize) Hyperextension Impact Resistance Caution With Elastic bands Isometrics Weights “Resistance is Useless”-Vogon guard, The Hitchhiker's Guide to the Galaxy, Douglas Adams

42. Toning Exercise • Low or non-resistance exercise • Walking, Elliptical, Bicycle • Swimming/Aquatherapy • ROM • Add repetitions, duration & frequency • Start low, go slow • Long horizon • Months to stop getting worse • Years to start getting better

43. Joint Instability • External bracing when needed • Joint stabilizing surgery? • Increased rate of immediate & short-term failure1,2 • Soft tissue fragility & wound dehiscence in Classical & Vascular EDS • Rombautet al. Arch Phys Med Rehabil. 2011;92:1106–12 • Rose et al. J Arthroplasty. 2004;19:190–6

44. Working Hypothesis Laxity Frequent minor subluxations Reflexive muscle spasm Osteoarthritis Pain Fatigue

45. Muscle Spasm • Myofascialrelease • Heat, massage, TENS, acupuncture… • Hours-days of relief • Special mattress • Water, air, viscoelastic foam • Medications • Skeletal muscle relaxers • Benzodiazepines (caution)

46. Working Hypothesis Laxity Frequent minor subluxations Reflexive muscle spasm Osteoarthritis Pain Fatigue

47. Pain: Etiology? • Myofascial spasm? • aching, throbbing, tight… • Neuropathic? • burning, tingling, electric… • DJD? • dull, aching, throbbing…

48. Pain: Passive & Mechanical Therapy • Myofascial release: ice, heat, massage, acupuncture/pressure, u/s, TENS… • Nerve blocks, joint/bursa injections • Limited benefit; can’t repeat indefinitely • Implantable stimulators • Other? (individualized therapy)

49. Pain: Medication • Analgesics & Anti-inflammatories • Acetaminophen, NSAIDs,Tramadol • Transdermallidocaine • Muscle Relaxers • Neuropathic pain control • Tricyclics, SNRIs, Anti-seizure • Opioids—last resort

50. Pain: Medication • Cocktail of multiple medications • Scheduled, preventive medication more effective than as-needed • Goal is to limit, but not eliminate pain • Pain management specialists