Dermatology MCQ - Genetic Disorders - Ehlers–Danlos Syndrome

A 20-year-old woman presents for evaluation of joint pain. She reports a lifetime history of easy bruising, and her ankles "roll" frequently. On examination, her skin is soft, velvety, and hyperextensible. You are able to passively hyperextend her fifth finger beyond 90 degrees (positive "thumb sign") and hyperextend her knees and elbows beyond 10 degrees. She has atrophic, papyraceous scars over her shins. Based on the 2017 International Classification, which subtype is most likely and what is the most common serious vascular complication?

A. Hypermobile EDS; risk of aortic dissection.
B. Classical EDS; risk of arterial rupture and hollow organ perforation.
C. Vascular EDS; risk of arterial rupture, dissection, and hollow organ perforation.
D. Kyphoscoliotic EDS; risk of ocular rupture and severe scoliosis.
E. Dermatosparaxis EDS; risk of severe skin fragility.

Correct Answer: C. Vascular EDS; risk of arterial rupture, dissection, and hollow organ perforation.

Answer and Explanation

The correct answer is C. While the description includes features common to several EDS types (bruising, hyperextensible skin, joint hypermobility), the presence of atrophic, papyraceous ("cigarette paper") scars is a hallmark of vascular EDS (vEDS), the most serious subtype. Although joint hypermobility in vEDS is often more limited to small joints, generalized hypermobility can occur. The most critical point is the severe vascular complication profile: patients with vEDS are at high risk for spontaneous arterial rupture (e.g., mesenteric, renal, splenic arteries), arterial dissection (including aortic), and rupture of hollow organs (uterus, colon). This life-threatening risk necessitates a distinct management approach.

Why the Other Options are Incorrect:

• A. Hypermobile EDS (hEDS): This is the most common type. It features generalized joint hypermobility and chronic pain, but the skin is usually only mildly hyperextensible and not fragile. It does not carry a risk of aortic dissection or arterial rupture. Atrophic scars are not a feature.

• B. Classical EDS (cEDS): This type is characterized by hyperextensible, fragile skin that splits easily ("cigarette paper" scars), and joint hypermobility. However, the most serious complications are related to significant skin fragility and joint dislocations. While arterial complications can occur, they are far less common and predictable than in vEDS.

• D. Kyphoscoliotic EDS (kEDS): This rare type is defined by congenital muscular hypotonia, severe progressive kyphoscoliosis, and a risk of ocular rupture (scleral fragility). The skin may be hyperextensible, but the clinical picture is dominated by the skeletal and ocular issues.

• E. Dermatosparaxis EDS (dEDS): This is an extremely rare type characterized by severe skin fragility with sagging, redundant skin, not primarily atrophic scars. It is not associated with the vascular risks of vEDS.

Additional High-Yield Information for Exams:

• 2017 International Classification: Recognizes 13 subtypes, defined by specific genetic causes, clinical criteria, and inheritance patterns.

• Genetics:

  • vEDS: Autosomal dominant, caused by mutations in the COL3A1 gene encoding type III collagen, a major component of blood vessels and hollow organs.

  • cEDS: Usually autosomal dominant, caused by mutations in COL5A1 or COL5A2 (type V collagen).

  • hEDS: No single gene identified yet; diagnosis is based on strict clinical criteria.

• Clinical Clues to vEDS:

  • Facies: Often thin, pinched nose, thin lips, prominent eyes.

  • Skin: Thin, translucent (visible veins), with characteristic atrophic scars.

  • Acrogeria: Premature aging of the skin on hands and feet.

  • History: Spontaneous pneumothorax, early-onset varicose veins, rupture of uterus or bowel.

• Differential Diagnosis: Other hereditary connective tissue disorders (Marfan syndrome, Loeys-Dietz syndrome) and other EDS subtypes. The specific scar type and vascular risk profile distinguish vEDS.

• Associated Conditions & Prognosis:

  • Prognosis in vEDS: Reduced life expectancy (median ~50 years) due to vascular or organ rupture. Pregnancy is high-risk for uterine rupture.

  • Prognosis in hEDS/cEDS: Normal lifespan with significant morbidity from chronic pain, joint instability, and dislocations.

• Management & Rationale:

  • Rationale: For vEDS, management is proactive surveillance and prevention of catastrophic events. For hEDS/cEDS, it is symptomatic and supportive.

  • vEDS-Specific Management:

    • Cardiovascular Surveillance: Annual CT angiography or MRA from late adolescence to screen for arterial aneurysms/dissections.

    • Medical Prophylaxis: Beta-blockers (e.g., celiprolol) or angiotensin II receptor blockers to reduce hemodynamic stress on vessels.

    • Surgical Caution: Extreme care with invasive procedures due to tissue fragility. Elective surgery should be avoided. Emergency surgery requires a specialized, conservative approach.

    • Genetic Counseling & Testing: Mandatory for at-risk family members.

  • General EDS Management: Physical therapy for joint stabilization, pain management, skin protection, and bracing. Patient education to avoid high-impact activities and joint overuse.