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
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 Syndrome
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HYPERMOBILITY 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
• High narrow
• Soft skin
palate
• Gastritis & IBS
• POTS & NMH
• Easy
bruisability
EDS Types
EDS: Revised Nosology
Beighton et al, Am J Med Genet (1998) 77:31-37
TYPE
OLD #
Hypermobility
III
Classical
I & II
Vascular
IV
Arthrochalasia
VIIA & B
Kyphoscoliosis
VI
Dermatosparaxis
VIIC
PATTERN
Autosomal
Dominant
Autosomal
Recessive
EDS: Hypermobility (III)
• “Benign Joint Hypermobility Syndrome”1
• Joint laxity
• Soft skin
• Easy bruisability
• Least severe, BUT paindisability
• Autosomal dominant
• Genetic cause unknown
1. Tinkle et al. Am J Med Genet A. 2009;149A:2368–70
Assessing Joint Laxity
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•
•
•
•
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Subjective
ROM
Hyperextension
Lateral instability
A/P instability
Varus/valgus
Telescoping
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•
•
•
Objective
Beighton 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 Scale
Palms to floor, knees straight: 1 point
Beighton Scale
o
Hyperextend elbow >10 : 1 point each
Radial
Styloid
Lateral
Humeral
Epicondyle
Humeral
Head
Beighton Scale
o
Hyperextend knee >10 : 1 point each
Greater
Trochanter
Lateral
Femoral
Condyle
Lateral
Malleolus
Beighton Scale
o
Dorsiflex 5th finger >90 :
1 point each
Appose thumb to forearm:
1 point each
Assessing Joint Laxity
Caveats
• 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
EDS: Classical - Skin
• 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 – 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 Laxity
WWW.OMIM.ORG
Differential Dx: Joint Laxity
Dozens other than EDS
• Marfan
• Loeys-Dietz
• Stickler
• Fragile X
• Turner
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
Pain
Osteoarthritis
Fatigue
Working Hypothesis
Laxity
Frequent minor subluxations
Reflexive muscle spasm
Pain
Osteoarthritis
Fatigue
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
“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 & shortterm failure1,2
 Soft tissue fragility & wound dehiscence
in Classical & Vascular EDS
1. Rombaut et al. Arch Phys Med Rehabil. 2011;92:1106–12
2. Rose et al. J Arthroplasty. 2004;19:190–6
Working Hypothesis
Laxity
Frequent minor subluxations
Reflexive muscle spasm
Pain
Osteoarthritis
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
Pain
Osteoarthritis
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 State
Common in EDS:
• Anxiety & Depression
• Low self-confidence
• Negative thinking
• Hopeless/helpless
• Desperation
• Low self-efficacy
Baeza-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 Management
High 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, 2012
http://www.ncbi.nlm.nih.gov/books/NBK
1279/#eds3
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Hypermobility Syndromes: Common But Often Overlooked