Ehlers Danlos Syndrome: Recognition, Diagnosis & Management
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Transcript of Ehlers Danlos Syndrome: Recognition, Diagnosis & Management
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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
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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
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Learning Objectives
• Recognize features of EDS• Initiate appropriate evaluation• Understand activity and other
management recommendations
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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
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Case 1: Exam• Palate: normal• Tender paralumbar spasm• Laxity in all joints
Pes planus Beighton score 8/9
• Skin normal
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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
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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
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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
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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
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Diagnoses
• Case 1: Ehlers Danlos Hypermobility Type• Case 2: Ehlers Danlos Hypermobility Type• Case 3: Isolated shoulder pain/instability
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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
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Ehlers Danlos Syndromes
• Heritable disorders of connective tissue
• Collagen• Prevalence 1:5000?
(probably more common)
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Ehlers Danlos Syndromes
• Joint laxity• Soft skin• Easy
bruisability
• High narrow palate
• Gastritis & IBS• POTS & NMH
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EDS Types
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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
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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
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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
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Beighton ScalePalms to floor, knees straight: 1 point
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Beighton ScaleHyperextend elbow >10o: 1 point each
Radial Styloid
Lateral Humeral
Epicondyle
Humeral Head
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Beighton ScaleHyperextend knee >10o: 1 point each
Lateral Malleolus
Lateral Femoral Condyle
Greater Trochanter
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Beighton Scale
Dorsiflex 5th finger >90o: 1 point each
Appose thumb to forearm: 1 point each
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Assessing Joint LaxityCaveats
• Age Young children: loose Older adults: stiff
• Sex: Female looser than male• Trauma/DJD/Surgery• Muscle tone or bulk• Guarding
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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
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• Very soft, sometimes doughy• Hyperelasticity Avoid loose skin Volar wrist— normal ~1 cm
EDS: Classical - Skin
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• Very soft, sometimes doughy• Hyperelasticity• Skin fragility Extensor surfaces
EDS: Classical - Skin
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• Molluscoid pseudotumor Thickened Hyperpigmented Elbows Knees
Atrophic Scars
EDS: Classical - Skin
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EDS: Classical – Soft Tissue
• Wound dehiscence• Soft tissue fragility (“wet toilet paper”)• Ligaments & Tendons• Rarely vascular tears
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EDS: Vascular (IV)• Joint laxity
Small >> large Wrists, fingers, ankles, toes
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EDS: Vascular (IV)• Joint laxity • Fragile skin• Thin translucent skin
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EDS: Vascular (IV)• Wound dehiscence• Dissection/rupture
Arteries Intestine Uterus Tendons
• Some never dissect/rupture 80% of 1st events ages 10-39
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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
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Differential Dx: Joint LaxityWWW.OMIM.ORG
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Differential Dx: Joint Laxity
• Marfan• Loeys-Dietz• Stickler• Fragile X• Turner
Dozens other than EDS
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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
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Management
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What We Know• Laxity & instability• Pain—out of proportion to exam/x-rays• Fatigue• Osteoarthritis (DJD)
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What We Don’t Know
Why?
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Working Hypothesis
Laxity
Frequent minor subluxations
Reflexive muscle spasm Osteoarthritis
Pain Fatigue
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Working Hypothesis
Laxity
Frequent minor subluxations
Reflexive muscle spasm Osteoarthritis
Pain Fatigue
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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
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“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
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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
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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
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Working Hypothesis
Laxity
Frequent minor subluxations
Reflexive muscle spasm Osteoarthritis
Pain Fatigue
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Muscle Spasm• Myofascial release
Heat, massage, TENS, acupuncture… Hours-days of relief
• Special mattress Water, air, viscoelastic foam
• Medications Skeletal muscle relaxers Benzodiazepines (caution)
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Working Hypothesis
Laxity
Frequent minor subluxations
Reflexive muscle spasm Osteoarthritis
Pain Fatigue
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Pain: Etiology?• Myofascial spasm?
aching, throbbing, tight…• Neuropathic?
burning, tingling, electric…• DJD?
dull, aching, throbbing…
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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)
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Pain: Medication• Analgesics & Anti-inflammatories
Acetaminophen, NSAIDs,Tramadol• Transdermal lidocaine• Muscle Relaxers• Neuropathic pain control
Tricyclics, SNRIs, Anti-seizure• Opioids—last resort
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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
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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…
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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
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Expectation ManagementHigh Bar
• No pain• No dislocations
or subluxations• “Normal” activity
tolerance
Low Bar• Less pain• Fewer dislocation
or subluxations• Improved activity
tolerance
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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…
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Resources• www.genereviews.org
clinically oriented reviews• www.omim.org
encyclopedic genetic catalog• www.ednf.org
patient support group
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Additional References & Information
Levy, GeneReviews, 2012http://www.ncbi.nlm.nih.gov/books/
NBK1279/#eds3