ABSTRACT: This case illustrates the rapid progression of multiple arterial abnormalities in a patient with vascular Ehlers-Danlos syndrome (EDS), through serial imaging with computed tomography (CT) over a 2-week time period. A right renal artery aneurysm required emergent intervention, whereas other renal and hepatic artery aneurysms were conservatively managed. A CT scan 16 months later showed regression of hepatic artery aneurysms and mild interval enlargement of a left renal artery aneurysm. This case emphasizes the variable outcomes and unpredictable nature of arterial complications in vascular EDS. To our knowledge, it is also first to demonstrate spontaneous regression of arterial aneurysms.

VASCULAR DISEASE MANAGEMENT 2014;11(11):E274-E280

Key words: computed tomography, aneurysm repair

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A 26-year-old white male with a history of vascular Ehlers-Danlos syndrome (EDS) presented to an outside hospital with sudden onset of right abdominal and flank pain. A contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis was performed and demonstrated an infarct in the lower pole of the right kidney. Of note, the renal arteries and hepatic arteries appeared grossly normal (Figures 1 and 2). The patient was then transferred to our institution for further management. 

His past medical history was significant for vascular EDS diagnosed at age 15. He had history of multiple, recurrent episodes of bilateral, spontaneous pneumothoraces and he underwent wedge resection and mechanical pleurodesis at age 19. His family history was significant for vascular EDS with acquired aneurysmal disease and valvular insufficiency. His father had vascular EDS and passed away in his 20s from a ruptured aortic aneurysm. 

Upon arrival to our institution the next day (day 1 of hospitalization), the patient was afebrile, normotensive, and in sinus bradycardia. On initial examination, he was a thin, pale and frail-appearing man. Physical examination was positive for tenderness to palpation in the right flank and right anterior abdomen. His hemoglobin was low at 11.7 g/dL, with normal white blood cell count and basic metabolic panel.

Further workup was conducted, including echocardiogram, blood cultures, urinalysis, and inflammatory markers, all of which were negative. Thus, the renal infarct was presumed to be the source of the patient’s pain and likely a complication of vascular EDS. The patient was conservatively managed with blood pressure management, intravenous hydration, and pain control. He remained clinically stable over the next few days. 

On day 4 of hospitalization, the patient experienced severe exacerbation of his abdominal pain. A CT of the abdomen was performed and revealed new aneurysmal dilatation of the anterior division of the right renal artery, a right perinephric hematoma, and a small left renal artery aneurysm (Figure 1B). The right lower pole renal infarct was grossly unchanged. There was also mild dilatation of the left and right hepatic artery branches (Figure 2B). In spite of these CT findings, the clinical service elected to continue conservative management with adequate pain control and the patient remained hemodynamically stable.

On day 8 of hospitalization, CT angiography (CTA) was performed for imaging follow-up and demonstrated increasing right perinephric hematoma and grossly similar appearance of the bilateral renal artery abnormalities (Figure 1C). There was, however, a new large saccular aneurysm involving the terminal branch of the anterior division of the right renal artery, which had developed since day 4 (Figures 3A and 3B). There was subtle contour irregularity of the aneurysm, suggestive of aneurysm rupture. In addition, CTA showed new fusiform aneurysms of the left and right hepatic artery branches (Fig 2 C). Because of the newly developed saccular aneurysm and the increased perinephric hematoma, Interventional Radiology (IR) was consulted for emergent coil embolization of the aneurysm.

However, immediately following the CTA study, the patient became severely hypotensive, with systolic blood pressure in the 60s, and with a drop in hemoglobin from 11.7 to 6.3 g/dL. He was transferred to the ICU and resuscitated. Once stabilized, the patient was taken to the interventional radiology suite for coil embolization of the large right renal artery aneurysm, felt to be the source of significant bleeding. 

Selective angiogram of the right renal artery revealed marked contour irregularity of the anterior division and a large saccular aneurysm in the terminal branch, both corresponding to the CTA findings (Figure 3C). Next, multiple metallic conventional and detachable microcoils were deployed through the main segment of the anterior division. Repeat angiogram confirmed successful and uncomplicated coil embolization of the main anterior division and the aneurysmal segment, with preservation of flow in the main renal artery and entire posterior division (Figure 3D). Following the procedure, the patient was transferred back to the ICU and remained hemodynamically stable. 

On day 11 of hospitalization, a CT abdomen and pelvis was performed for persistent abdominal pain and a tense, distended abdomen. The CT scan showed large volume hemoperitoneum, without evidence of active bleeding. As expected, there was evolving infarction of the majority of the anterior and central right kidney status post embolization (Figure 1D). The hepatic artery aneurysms had also increased in size (Figure 2D). General surgery was consulted and the patient underwent exploratory laparotomy with evacuation of two liters of hemoperitoneum. The postoperative course was uneventful and the patient was eventually discharged from the hospital in good condition. 

The patient was lost to follow-up at our institution. However, 16 months later, he presented to our emergency department with symptoms of chest pain. A CTA of the chest was performed and demonstrated right lower lobe airspace consolidation. Interestingly, the previously seen right hepatic artery aneurysm was no longer visible at the same anatomic level as on prior scans, despite good visualization of other hepatic artery branches in the right hepatic lobe. The left hepatic artery branch was faintly seen and normal in caliber (Figure 2E). These findings illustrated spontaneous regression of the hepatic artery aneurysms. Per medical records, there was no interval therapy for these lesions. However, this CTA also showed evidence of several metallic coils in the left renal artery branches, proximal and distal to the existing left renal artery aneurysm. The aneurysm was still perfused and appeared slightly larger since prior scan (Figure 1E). There were no perfusion defects in the left kidney. Thus, the coil packing was insufficient for vessel occlusion. There was brief documentation that the patient had undergone therapy for the left renal artery aneurysm at an outside institution, though the date and details of the procedure (e.g., whether emergent or elective) were not provided. 

Discussion

The natural history and prognosis of vascular EDS differs significantly from the other types of EDS. Due to extreme vessel fragility, patients with vascular EDS carry a worse prognosis given propensity towards life-threatening vascular complications.¹ Complications include arterial aneurysms, dissections, and ruptures, which can result in parenchymal infarctions and catastrophic hemorrhage.² 

The management of patients with vascular EDS is challenging. Historically, risks of procedure-related complications and operative mortality have been relatively high.^1,3,4 Asymptomatic patients are traditionally managed conservatively such as with blood pressure management. However, there is no general consensus on the optimal management of large asymptomatic or minimally symptomatic vascular complications.^3,4,5 Surgical or endovascular treatments are typically reserved for cases of imminent or life-threatening complications.^2,4,6 

Noninvasive imaging is an invaluable tool for the evaluation of these patients.^7,8 But there is controversy about the role of routine imaging surveillance of vascular EDS.⁴ Nevertheless, we present a unique case where early, serial CT imaging was performed and illustrated the rapid progression of arterial abnormalities, namely aneurysms, over several days. The exact precipitant of the rapid progression of arterial complications in patients with vascular EDS is unknown. One theory is that endothelial cell damage may be the initial event in the disease progression.⁹ However, for our patient, no clear precipitating factor was identified.

The progression of vascular lesions have previously been reported over time periods of several months.^6,10 In our case, the right renal artery aneurysm led to significant bleeding and prompted emergent therapy within a 2-week period, emphasizing the fragile condition of symptomatic patients who are initially managed conservatively. Clinicians must be prepared to intervene prior to catastrophic outcomes. 

To our knowledge, this case is the first to report spontaneous regression of aneurysms on imaging in a patient with vascular EDS. While the hepatic artery aneurysms developed rapidly during hospitalization, they remained clinically occult and were no longer evident on the CTA study 16 months later. On the other hand, the CTA revealed persistence and interval enlargement of the left renal artery aneurysm. 

In summary, the different clinical manifestations and outcomes of the arterial abnormalities in this patient highlight the variable and unpredictable nature of vascular complications in patients with vascular EDS. While rapid progression of arterial abnormalities is the more commonly recognized and reported clinical course, the arterial abnormalities may be clinically occult for some time, or even appear to spontaneously regress. This underscores the difficulty in establishing specific guidelines for routine imaging surveillance and treatment recommendations for these patients, particularly for those who are asymptomatic or mildly symptomatic.

Editor’s note: Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no financial relationships or conflicts of interest regarding the content herein.

Manuscript submitted May 6, 2014; provisional acceptance given June 20, 2014; final version accepted July 16, 2014.

Address for correspondence: Danielle M. Chan, MD, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 702 Barnhill Drive, Room 1053, Indianapolis, IN 46202. Email: dmchan@iupui.edu.

References

1. Cikrit DF, Miles JH, Silver D. Spontaneous arterial perforation: the Ehlers-Danlos specter. J Vasc Surg. 1987;5(2):248-255.
2. Germain DP. Ehlers-Danlos syndrome type IV. Orphanet J Rare Dis. 2007;19(2):32.
3. Oderich GS, Panneton JM, Bower TC, et al. The spectrum, management and clinical outcome of Ehlers-Danlos syndrome type IV: a 30-year experience. J Vasc Surg. 2005;42(1):98-106. 
4. Bergqvist D, Björck M, Wanhainen A. Treatment of vascular Ehlers-Danlos syndrome: a systematic review. Ann Surg. 2013;258(2):257-261.
5. Brooke BS, Arnaoutakis G, McDonnell NB, Black JH 3rd. Contemporary management of vascular complications associated with Ehlers-Danlos syndrome. J Vasc Surg. 2010;51(1):131-138. 
6. Mortani Barbosa Jr EJ, Pyeritz RE, Litt H, Desjardins B. Vascular Ehlers-Danlos syndrome presenting as rapidly progressive multiple arterial aneurysms and dissections. Am J Med Genet A. 2011;155A(12):3090-3094.
7. Zilocchi M, Macedo TA, Oderich GS, Vrtiska TJ, Biondetti PR, Stanson AW. Vascular Ehlers-Danlos syndrome: imaging findings. Am J Roentgenol. 2007;189(3):712-719.
8. Chu LC, Johnson PT, Dietz HC, et al. Vascular complications of Ehlers-Danlos syndrome: CT findings. AJR Am J Roentgenol. 2012;198(2):482-497.
9. Asherson RA, Bosman C, Tikly M, Spiro F, Pope FM. Ehlers-Danlos syndrome type IV in a young man. J Rheumatol. 2006;33(10):2091-2096.
10. Adami P, Manzoni P, Rohmer P. [Evolutive aneurysms in type IV Ehlers Danlos’ syndrome] (in French). Abstract. Ann Radiol (Paris). 1993;36(2):129-133.