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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. Disclosures. No relevant financial relationships - PowerPoint PPT Presentation
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Ehlers Danlos Syndrome: Recognition, Diagnosis &
ManagementHoward P. Levy, M.D., Ph.D.
Assistant Professor, Johns Hopkins University
Johns Hopkins Adolescent Medicine Grand Rounds
Baltimore, MDOctober 12, 2012
Disclosures
1. No relevant financial relationships
2. 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
Learning Objectives
• Recognize features of EDS• Initiate appropriate evaluation• Understand activity and other
management recommendations
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
Case 1: Exam• Palate: normal• Tender paralumbar spasm• Laxity in all joints
Pes planus Beighton score 8/9
• Skin normal
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
Case 2: Exam• Palate: high, narrow, intact• Tender left trapezius spasm• Laxity
Shoulders, elbows, wrists, fingers Left knee only (muscular, especially LE) Pes planus Beighton score 8/9
• Skin normal
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
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
Diagnoses
• Case 1: Ehlers Danlos Hypermobility Type• Case 2: Ehlers Danlos Hypermobility Type• Case 3: Isolated shoulder pain/instability
Ehlers Danlos SyndromeHYPERMOBILITY TYPE (III)
• Joint laxity• Pain (arthralgia, myalgia, headache)• Fatigue• Worse with resistance & activity• High narrow palate/dental crowding• Easy bruising, mildly soft skin
Ehlers Danlos Syndromes
• Heritable disorders of connective tissue
• Collagen• Prevalence 1:5000?
(probably more common)
Ehlers Danlos Syndromes
• Joint laxity• Soft skin• Easy
bruisability
• High narrow palate
• Gastritis & IBS• POTS & NMH
EDS Types
EDS: Revised Nosology Beighton et al, Am J Med Genet (1998) 77:31-37
TYPE OLD # PATTERNHypermobility III
Autosomal Dominant
Classical I & IIVascular IV
Arthrochalasia VIIA & BKyphoscoliosis VI Autosomal
RecessiveDermatosparaxis VIIC
EDS: Hypermobility (III)• “Benign Joint Hypermobility Syndrome”1
• Joint laxity• Soft skin• Easy bruisability• Least severe, BUT paindisability• Autosomal dominant• Genetic cause unknown
1. Tinkle et al. Am J Med Genet A. 2009;149A:2368–70
Assessing Joint LaxitySubjective
• ROM• Hyperextension• Lateral instability• A/P instability• Varus/valgus• Telescoping
ObjectiveBeighton Scale1
• 9 possible points• “+” = 5 or more • Doesn’t assess
all joints• Not “Gold Std”
1. Beighton et al. Ann Rheum Dis. 1973;32:413–8
Beighton ScalePalms to floor, knees straight: 1 point
Beighton ScaleHyperextend elbow >10o: 1 point each
Radial Styloid
Lateral Humeral
Epicondyle
Humeral Head
Beighton ScaleHyperextend knee >10o: 1 point each
Lateral Malleolus
Lateral Femoral Condyle
Greater Trochanter
Beighton Scale
Dorsiflex 5th finger >90o: 1 point each
Appose thumb to forearm: 1 point each
Assessing Joint LaxityCaveats
• Age Young children: loose Older adults: stiff
• Sex: Female looser than male• Trauma/DJD/Surgery• Muscle tone or bulk• Guarding
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. Symoens et al. Hum Mutat. 2012; 33:1485–1493
• Very soft, sometimes doughy• Hyperelasticity Avoid loose skin Volar wrist— normal ~1 cm
EDS: Classical - Skin
• Very soft, sometimes doughy• Hyperelasticity• Skin fragility Extensor surfaces
EDS: Classical - Skin
• Molluscoid pseudotumor Thickened Hyperpigmented Elbows Knees
Atrophic Scars
EDS: Classical - Skin
EDS: Classical – Soft Tissue
• Wound dehiscence• Soft tissue fragility (“wet toilet paper”)• Ligaments & Tendons• Rarely vascular tears
EDS: Vascular (IV)• Joint laxity
Small >> large Wrists, fingers, ankles, toes
EDS: Vascular (IV)• Joint laxity • Fragile skin• Thin translucent skin
EDS: Vascular (IV)• Wound dehiscence• Dissection/rupture
Arteries Intestine Uterus Tendons
• Some never dissect/rupture 80% of 1st events ages 10-39
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
Differential Dx: Joint LaxityWWW.OMIM.ORG
Differential Dx: Joint Laxity
• Marfan• Loeys-Dietz• Stickler• Fragile X• Turner
Dozens other than EDS
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
Management
What We Know• Laxity & instability• Pain—out of proportion to exam/x-rays• Fatigue• Osteoarthritis (DJD)
What We Don’t Know
Why?
Working Hypothesis
Laxity
Frequent minor subluxations
Reflexive muscle spasm Osteoarthritis
Pain Fatigue
Working Hypothesis
Laxity
Frequent minor subluxations
Reflexive muscle spasm Osteoarthritis
Pain Fatigue
Joint InstabilityMUSCLE 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
“Resistance is Useless” -Vogon guard, The Hitchhiker's Guide to the
Galaxy, Douglas Adams
Avoid (minimize)• Hyperextension• Impact• Resistance
Caution With• Elastic bands• Isometrics• Weights
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
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
1. Rombaut et al. Arch Phys Med Rehabil. 2011;92:1106–122. Rose et al. J Arthroplasty. 2004;19:190–6
Working Hypothesis
Laxity
Frequent minor subluxations
Reflexive muscle spasm Osteoarthritis
Pain Fatigue
Muscle Spasm• Myofascial release
Heat, massage, TENS, acupuncture… Hours-days of relief
• Special mattress Water, air, viscoelastic foam
• Medications Skeletal muscle relaxers Benzodiazepines (caution)
Working Hypothesis
Laxity
Frequent minor subluxations
Reflexive muscle spasm Osteoarthritis
Pain Fatigue
Pain: Etiology?• Myofascial spasm?
aching, throbbing, tight…• Neuropathic?
burning, tingling, electric…• DJD?
dull, aching, throbbing…
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)
Pain: Medication• Analgesics & Anti-inflammatories
Acetaminophen, NSAIDs,Tramadol• Transdermal lidocaine• Muscle Relaxers• Neuropathic pain control
Tricyclics, SNRIs, Anti-seizure• Opioids—last resort
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
Pain: Psychology“90% of the game is half mental”
-Yogi Berra• The underlying problems are real• But pain is a subjective experience
• Emotional State• Goals and expectations• Fears• Avoidance, disability, isolation• others…
Emotional StateCommon in EDS:• Anxiety & Depression• Low self-confidence• Negative thinking• Hopeless/helpless• Desperation• Low self-efficacyBaeza-Velasco et al (2011) Rheumatol Int. 31:1131; Branson et al (2011) Harv Rev Psychiatry 19:259; Castori et al(2010) Am J Med Genet A. 152A:556; Hagberg et al (2004) Orthod Craniofac Res. 7:178; Rombaut et al (2011) Arthritis Rheum. 63:1979
Expectation ManagementHigh Bar
• No pain• No dislocations
or subluxations• “Normal” activity
tolerance
Low Bar• Less pain• Fewer dislocation
or subluxations• Improved activity
tolerance
Pain: Psychological Tx• Relationships with healthcare providers.
Clinician must validate symptoms as real Patient must trust that psych components
play a role• Counseling
Depression, anxiety… Accepting & coping w/pain & dysfunction
• Cognitive Behavioral Therapy, conscious relaxation, hypnosis, meditation…
Resources• www.genereviews.org
clinically oriented reviews• www.omim.org
encyclopedic genetic catalog• www.ednf.org
patient support group
Additional References & Information
Levy, GeneReviews, 2012http://www.ncbi.nlm.nih.gov/books/
NBK1279/#eds3
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