1. Ehlers Danlos Syndrome
Sarah V. Kelly, M.D.

2. Case Presentation
52 year-old married female dentist with two adult children
CC: chronic diarrhea
PMH: Depression, generalized anxiety, “thyroid disease”, “fibromyalgia” and peri-menopause
Medications: fluoxetine (prozac) and levothyroxine (synthroid)
Allergies: NKDA
Surgical history: None, 2 NSVDs with no complications

3. Case Presentation
Intermittent diarrhea and constipation (IBS-like symptoms)
Wonders if GI symptoms related to “something I’m eating” or an infection (possibly related to travel)?
Denies fevers, chills or night sweats. No significant weight loss.
c/o significant fatigue that has not improved with treatment of autoimmune thyroid disease (Hashimoto’s thyroiditis)

4. Review of Systems
Expresses concern about increasing episodes of debilitating headaches and difficulty focusing at times
Occasional palpitations, particularly when “standing up too quickly”
Others have labeled her as a “hypochondriac” or implied that her symptoms are not “real”
Recently diagnosed with fibromyalgia
Notices similar symptoms in her daughter

5. What is it?
“If you cannot connect the issues, think connective tissues” – Laura Bloom.

6. EDS: What is it?
A group of inherited disorders caused by qualitative and/or quantitative abnormalities in collagen production
Collagen is present in nearly every tissue and organ system in the body
EDS associated with many widespread complications and symptoms; tissues often involved are skin, joints, and blood vessel walls
There are 6 major types that vary in their specific cause and presentation (dependent on the form of collagen affected)
Recorded prevalence of 1 in 2,500 (often misdiagnosed)
Most cases inherited in autosomal dominant pattern

7. Major Symptoms Stretchy, loose, and/or “velvety” skin
Flexible joints with hypermobility (causes chronic joint pain, damage and reactive muscle pain)
Abnormal wound healing
Joint dislocations and/or partial dislocations (aka subluxations)
Easy bruising
Muscle pain and weakness
Heart and vascular problems such as aneurysms, MVP, aortic root dilatation
Organ rupture, hernia

8. Joint and Skin Findings

11. Associated Conditions
Autoimmune thyroid disease
Chronic pelvic pain from endometriosis and/or pelvic congestion syndrome
Depression, generalized anxiety disorder and obsessive compulsive disorder
Chiari malformation
GI symptoms/IBS related to mast cell activation disorder (MCAD) and “leaky gut”
Autonomic dysfunction from Postural Orthostatic Tachycardic Syndrome (POTS)
Temporomandibular Joint Dysfunction (aka TMJ)
Chronic (daily) headache
Reduced responsiveness to anesthetics and opiate pain medication
Clumsiness, falls, trauma, etc. due to decreased proprioception and strength

12. Natural History Childhood Young adulthood
Diagnosis of EDS in children requires high suspicion
EDS kids often have chronic, repetitive complaints of non- specific pain (“growing pains”, joint aching, headaches) and FATIGUE (? Depression)
May have increased risk of fractures
Young adulthood
Relatively asymptomatic
Hypermobility of childhood persists or progresses
Adulthood = Restrictive phase of disease, degenerative arthritis predominates

13. Differential Diagnoses
Fibromyalgia
Lyme disease
Seronegative arthritis
Munchausen’s Syndrome, Conversion Disorder
Marfan Syndrome
Osteogenesis Imperfecta
Other rare conditions: Loeys-Dietz Syndrome, Stickler Syndrome, Williams Syndrome, Aarskog-Scott Syndrome, Fragile X Syndrome, Achondroplasia, hypochondroplasia

14. Classical Type (Types I & II)
Generalized hyperextensibility of joints and skin
Easy bruising, hemarthroses
Poor wound healing and retention of sutures
Congenital dislocation of hips
Scoliosis
Mitral valve prolapse

15. EDS – Classic Type

16. Hypermobility Type (Type III)
Most common type (reported in up to 1 in 5,000, probably MUCH higher)
Exact cause unknown; no genetic test available
Autosomal dominant inheritance
Cardinal feature: Joint hyper-extensibility
Chronic degenerative joint disease with advanced, premature osteoarthritis
Less skin involvement
Mitral valve prolapse

17. EDS - Hypermobility

18. EDS - Hypermobility

19. Vascular Type (Type IV)
Most serious type (1 in 250,000)
Prone to ruptured/dissected arteries and aneurysms, intestinal and uterine rupture
Easy bruising
Visible veins beneath thin, translucent skin
Characteristic facies: protruding eyes, thin nose/lips, sunken cheeks, small chin
Joint involvement variable
Relative deficiency in type III collagen

20. EDS – Vascular Type

21. Kyphoscoliosis Type (Type VI) Arthrochalasia Type (Type VIIA/VIIB) Dermatosparaxis Type (Type VIIC)

22. Kyphoscoliosis Type

23. Diagnosis Family History/Pedigree Physical Exam/History
Laboratory studies: rule out rheumatologic disease and assess disease status
Genetic testing (PCR) for known disease- causing mutations (classical, vascular, kyphoscoliosis and arthrochalasis types)
Others testing: skin biopsy, urine test (kyphoscoliosis type), prenatal and pre- implantation testing

24. Treatment No specific cure available
Goal: Manage symptoms and prevent complications
Important EDS screening:
Echocardiogram
DEXA scan
CNS imaging (including vascular scans)
Patient education and genetic counseling
Rehabilitation and Maintenance – PT/OT, aquatic therapy
Postural training and body awareness
Chronic pain management
Orthopedic surgery (in skilled hands)

25. Non-restorative Sleep
Disease Cycle of EDS
Joint pain & Fatigue
Non-restorative Sleep
Stress/Anxiety
Depression
Decreased mobility
Disruption in
Neurotransmitters
Adrenal Fatigue &
Hormonal Imbalances

26. Managing Hypermobility
Goal: Prevention of disease progression and disability, restoration of normal form and function
PT/OT – Strengthening muscles within a normal (reduced) range of motion
Splinting when necessary for healing
Avoidance of high impact activities or activities that promote hypermobility (dance, gymnastics, yoga, etc.)

27. What is helpful? Adhering to a healthy (paleo-like) LIFESTYLE
Remaining mentally and physically active
Getting enough….but not too much…rest
Social support
Cognitive behavioral therapy
Mindful selection of supplements and medications
Medical THC ?

28. References
Klippel, John. Primer on the Rheumatic Diseases. Edition Atlanta, GA: Arthritis Foundation; 2001:
Ramanath VS, Oh JK, Sundt III TM, Eagle KA. Acute Aortic Syndromes and Thoracic Aortic Aneurysm. Mayo Clinic Proceedings. 2009; 84(5):
Beighton P,  DePaepe A,  Steinmann B,  Tsipouras P  and  Wenstrup RJ.  Ehlers-Danlos Syndromes: Revised Nosology,  Villefranche, 1977.  Am J Med Gen 1998; 77: 31-37