Case Report, Vascular-Interventional

Ehlers-Danlos syndrome (EDS) type IV

By Karl S. Chiang, MD; Bobby C. Walters, Jr., MD
Volume: 32 Number: 5 May 2003

Applied Radiology Online

Summary:

The patient is a 13-year-old boy who was seen in another hospital's emergency department after awakening at night with an episode of sharp "stabbing" chest pain. The pain involved the left shoulder and caused shortness of breath. A chest X-ray revealed mediastinal widening, and a contrast-enhanced CT of the chest (Figure 1A) showed diffuse mediastinal soft-tissue densities, especially around the aorta. He was subsequently transferred to the pediatric intensive care unit (PICU).

Admission history and physical examination were notable only for premature birth and pneumonia at 6 months of age, as well as a slightly asymmetrical chest with prominence of the left hemithorax. At this point, Hodgkin's lymphoma was the working diagnosis and fine needle aspiration was performed under CT guidance. The specimen obtained was not diagnostic and a thoracoscopic/open biopsy was scheduled to be performed in 2 days. He was transferred to the general pediatric floor but had to return to the PICU on the following day because of dyspnea and a mild increase in neck swelling. His cardiac examination remained normal.

Diagnosis:

Ehlers-Danlos syndrome (EDS) type IV

Imaging findings:

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 (Figure 3B), which is consistent with that found on the CT scan that was obtained earlier (Figure 1B). A right subclavian artery occlusion was also noted.

CASE FOLLOW-UP

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 disorder.

Discussion:

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 rare.⁶

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.

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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. 1993;46:278-283.

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.

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5. Herman TE, McAlister WH. Cavitary pulmonary lesions in type IV Ehlers-Danlos syndrome. Pediatr Radiol. 1994;24:263-265.

6. Byers PH. Ehlers-Danlos syndrome. In: Stansbury JB. Metabolic Basis of Inherited Disease. 6th ed. New York: McGraw-Hill; 1989:2824-2832.

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. 1996;162:163-170.

9. Cikrit DF, Miles JH, Silver D. Spontaneous arterial perforation: The Ehlers-Danlos specter. J Vasc Surg. 1987;5:248-255.

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.