Ehlers-Danlos syndrome (EDS) type IV
A repeat chest CT identified an "outpouching of the aorta" (Figure
1B), which was not present on the previous study. A thoracic
aortagram confirmed a defect in the left lateral-posterior aorta
below the left subclavian origin without evidence of dissection or
diffuse aneurysmal dilation (Figure 2). Initially, the defect was
believed to represent a pseudoaneurysm with tumor encasing the
aortic arch and descending aorta. Additional medical history,
pursued after the aortogram, revealed that approximately 1 year
earlier the patient had complained of severe chest pain, bruising
of the right chest and neck, and coolness of his right arm for 1 to
2 weeks after throwing a ball. At this point, a connective tissue
disorder was entertained as a cause of the leaking aortic
pseudoaneurysm with hematoma. Thoracic aorta repair was scheduled,
as the patient's hemoglobin had been decreasing.
An MRI was planned for the following morning. During the night,
however, an increase in his left pleural effusion with associated
left lung collapse prompted an emergency MRI/MR angiography. This
study showed an intramural hematoma of the descending aorta (Figure
3A) as well as a defect in the posterior wall of the aorta (Figures
3B and 3C), which is consistent with that found on the CT scan that
was obtained earlier (Figure 1B). A right subclavian artery
occlusion was also noted.
The patient was taken to surgery the morning the MRI was
performed and a tubular Dacron graft was placed distal to the left
subclavian take-off to approximately 3 cm above the diaphragm.
On the first postoperative morning, he had massive bleeding via
his endotracheal tube followed by bradycardia and loss of 700 mL of
blood via left chest tubes, subsequent to inflation of a pulmonary
artery catheter balloon for cardiac output measurement. Rupture of
the pulmonary artery was suspected. He was resuscitated. In the
ensuing 24 hours he developed acute respiratory distress syndrome,
requiring high-frequency jet ventilation, and renal failure,
requiring dialysis. Despite inotropic and pressor support, and
hemodialysis, he died on the third postoperative day. Autopsy
revealed findings consistent with a suspected connective tissue
Ehlers-Danlos syndrome is a disorder of connective tissue that
can be classified into at least ten types on the basis of clinical,
genetic, and biochemical information.1 Type IV is the
most severe form of EDS and is also known as the
ecchymotic-arterial variant. In these patients there is virtually
always a defect in the synthesis, secretion, or structure of type
III collagen. This form of collagen is most abundant in skin, large
arteries, and hollow organs.2,3 Therefore, patients with
EDS type IV are at significant risk for uterine rupture during
pregnancy, gastrointestinal rupture, and, most frequently, arterial
rupture. Clinically, this disorder is characterized by thin,
translucent skin with a prominent venous network and a tendency
toward easy bruising. Characteristic facial features are often
present and include large, excavated eyes and a thin pinched nose.
Their hands and feet are often acrogeric and there is minimal joint
hypermobility, no skin hyperextensivity, and normal
scarring.4,5 There is no known medical treatment to
increase the production of type III collagen. However, ascorbic
acid (1 to 2 grams per day) may increase the synthesis of collagen
and therefore provide slightly more of the normal type III
collagen. Those affected typically die during the third to fifth
decade of life; survival beyond 50 years of age is
Vascular complications, as a result of the collagen defect in
the walls of vessels, include aneurysms, dissections, varicosities,
and arteriovenous fistulas; ruptures are the most severe
complication.7 There is a 50% rate of perforation of
large and medium-sized arteries.7 Rupture of
nonaneurysmal arteries are more likely to result in death, such as
in this case, as compared with rupture of known
aneurysms.8 Unfortunately, the diagnosis of EDS type IV
is often unsuspected at clinical presentation. Only 16% of patients
with EDS type IV are known to have the diagnosis before
presentation with a vascular complication.9
Ideally, early diagnosis and surgical treatment could improve
short-term outcomes. Stent-graft repair of pseudoaneuryms may be
attempted, but ligation may be more effective and
definitive.10 This patient's diagnosis was made early
due to the history obtained from the patient's family and good
cross-sectional imaging. This resulted in successful surgical
repair, which was performed in a timely fashion. Unfortunately, the
patient's death was caused by the rupture of another nonaneurysmal
pulmonary artery, as is often the case with EDS type IV.
1. Nerlich AG. Pathomorphological and biochemical alterations in
Ehlers-Danlos syndrome type IV. Pathol Res Prac.
2. Narcisi P, Wu Y, Tromp G, et al. Single base mutation that
substitutes glutamic acid for glycine 1021 in the COL3A1 gene and
causes Ehlers-Danlos syndrome type IV. Am J Med Genet.
3. Liu X, Wu H, Byrne M, et al. Type III collagen is crucial for
collagen I fibrillogenesis and for normal cardiovascular
development. Proc Natl Acad Sci. 1997;94:1852-1856.
4. Yeowell HN, Pinnell SR. The Ehlers-Danlos syndrome. Semin
5. Herman TE, McAlister WH. Cavitary pulmonary lesions in type
IV Ehlers-Danlos syndrome. Pediatr Radiol.
6. Byers PH. Ehlers-Danlos syndrome. In: Stansbury JB.
Metabolic Basis of Inherited Disease. 6th ed. New York:
7. Sherry RM, Fisch A, Grey DP, Lubbock CA. Embolization of a
hepatoportal fistula in a patient with Ehlers-Danlos syndrome and
colon perforation. Surgery. 1992;111:475-478.
8. Bergquist D. Ehlers-Danlos type IV syndrome: A review from a
vascular surgical point of view. Eur J Surg.
9. Cikrit DF, Miles JH, Silver D. Spontaneous arterial
perforation: The Ehlers-Danlos specter. J Vasc Surg.
10. Hovsepiam DM, Aguilar RL, Sicard GA, et al. Stent-graft
failure in a patient with a connective tissue disorder. J Vasc
Intervent Radiol. 1997;8:789-793.
Prepared by Karl S. Chiang, MD, Clinical
Associate Professor of Radiology, Brody School of Medicine, East
Carolina University, Greenville, NC; and Bobby C. Walters,
Jr., MD, Radiology Resident, Medical University of South
Carolina, Charleston, SC.