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INTRODUCTION

The vascular type of Ehlers-Danlos syndrome (vEDS) is the most severe form of Ehlers-Danlos syndrome. Patients with vEDS show deficiency or abnormality in type III collagen re-sponsible for production of vascular structures. The disease causes organs to become fragile and vulnerable to rupture, which may lead to sudden death. The diagnosis of vEDS is of-ten delayed until a catastrophic complication occurs or is dis-covered in postmortem examination. Here we report an un-usual case of an isolated pulmonary hematoma mimicking a lung tumor in an 18-year-old man which turned out to be the initial finding of vEDS.

CASE REPORT

An 18-year-old man, who had been in good health, was re-

ferred to our hospital from another hospital due to recurrent scanty hemoptysis. Physical examination revealed a normal ap-pearance of the face and skin. His parents were healthy without relevant past medical history. The results of laboratory exami-nations including coagulation study were normal. Chest radio-graph showed a well-defined mass in the medial aspect of the left upper lung zone (Fig. 1A). Chest computed tomography (CT) demonstrated a well-defined, non-enhancing mass of rel-atively high attenuation (about 75 Hounsfield units) in the left upper lobe (Fig. 1B). The initial impression was a benign tumor that had originated from lung parenchyma. On the lung CT scan, the adjacent lung parenchyma was clear and there was no evidence of blood aspiration or bronchiectasis. For pathological confirmation of the diagnosis, surgical removal of the mass was performed using video-assisted thoracoscopic surgery which revealed an old hemorrhage and benign fibrosis. There were no complications during or immediately after surgery. Six months

Case ReportpISSN 1738-2637J Korean Soc Radiol 2012;67(5):367-370

Received July 30, 2012; Accepted September 5, 2012Corresponding author: Ki-Nam Lee, MDDepartment of Radiology, Dong-A University Medicine Center, Dong-A University College of Medicine, 26 Daesingongwon-ro, Seo-gu, Busan 602-715, Korea.Tel. 82-51-240-5367 Fax. 82-51-253-4931E-mail: gnlee@dau.ac.kr

Copyrights © 2012 The Korean Society of Radiology

The vascular type of Ehlers-Danlos syndrome (vEDS) is an uncommon inherited dis-order characterized by abnormalities in type III collagen, presenting itself as arterial dissection or rupture. We report a case of an isolated pulmonary hematoma mim-icking a lung tumor in an 18-year-old man which turned out to be the initial find-ing of vEDS. Pneumothorax and hemothorax occurred repeatedly for 15 months following the surgical removal of the mass, and were treated by repeated left upper and lower lobectomy and thoracotomy. The diagnosis of vEDS was confirmed by pathologic and genetic studies.

Index termsEhlers-Danlos Syndrome Lung CT

An Isolated Pulmonary Hematoma Mimicking a Lung Tumor as the Initial Finding of Vascular Ehlers-Danlos Syndrome1

폐종양으로 오인된 폐혈종이 초기소견으로 발현된 혈관성 엘러스-단로스 증후군1

Eun-Ju Kang, MD1, Ki-Nam Lee, MD1, Pil Jo Choi, MD2, Chang-Seok Ki, MD3

Departments of 1Radiology, 2Thoracic Surgery, Dong-A University Medicine Center, Dong-A University College of Medicine, Busan, Korea3Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Vascular Ehlers-Danlos Syndrome

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III collagen gene (COL3A1) was performed after obtaining in-formed consent from the patient. A heterozygous mutation in exon 13 at c.889 of the COL3A1 gene from guanine to adenine (c.899G > A) was detected (Fig. 1F). This mutation converted glycine to aspartate at amino acid position 300 (Gly300Asp). Based on these findings, a diagnosis of vEDS was made.

Eleven months after the initial presentation, the patient de-veloped dyspnea and the chest radiograph at this time showed a right-sided pneumothorax. He was treated via chest tube in-sertion without any complications. He again developed dys-pnea with hemoptysis after 2 months, and a large hematoma with surrounding hemorrhage was detected on chest radiogra-phy (Fig. 1G). A chest CT scan detected small air cavities in the large hematoma accompanied with pneumothorax (Fig. 1H). Because the patient’s vital signs were unstable, he was managed only by conservative therapies, such as controlling blood pres-sure by keeping him in an absolute bed rest state in the inten-sive care unit. Operation or endovascular treatment was not considered at this point. After receiving conservative manage-

after discharge, the patient revisited the hospital due to dys-pnea, and his chest radiograph revealed a left-sided pneumo-thorax (Fig. 1C). A chest tube was inserted, and chest CT showed a huge cavity with internal air-hemorrhage level in the left lower lobe, and a smaller cavity surrounded by patchy ground-glass opacity in the left upper lobe (Fig. 1D, E). A large amount of blood was continuously drained (> 150 mL/min) through the inserted chest tube, and the huge hemorrhagic cavity was shown to almost completely occupy the left lower lobe, for which the patient underwent a left lower lobectomy. Immediately after this surgical procedure, hemothorax and massive hemoptysis developed, which were treated with an ad-ditional operation of a left upper lobectomy and thoracic drain-age. The lung specimen revealed an organized hematoma with cavity formation, and an old and fresh intraparenchymal hem-orrhage. There was no evidence of vasculitis or bronchiectasis. A genetic study was performed in order to determine the fra-gility of the underlying lung tissue that may have caused the re-current hematoma and pneumothorax. An analysis of the type

F

B C

G

D

E H

A

Fig. 1. Sequential chest radiograph and CT images of an 18-year-old man with vascular Ehlers-Danlos syndrome.A. Chest radiograph shows a well-defined mass in the medial aspect of the left upper lung zone. B. Chest computed tomography (CT) demonstrates a well-defined, non-enhancing mass of relatively high attenuation (about 75 Hounsfield units) in the left upper lobe. C-E. Chest radiograph and CT obtained six months later. The chest radiograph reveals a left-sided pneumothorax (C). A chest tube was inserted, and chest CT shows a huge cavity with internal air-hemorrhage level in the left lower lobe and a small cavity surrounded by patchy ground glass opacity in the left upper lobe (D, E). F. Direct sequencing analysis in the patient demonstrates a heterozygous variation (c.899G > A) resulting in a p.Gly300Asp mutation in the COL3A1 gene. G, H. Chest radiograph and CT obtained thirteen months after the initial presentation. A large hematoma with surrounding hemorrhage is de-tected on chest radiography (G). The chest CT scan shows small air cavities in the large hematoma and a small amount of pneumothorax (H).

Eun-Ju Kang, et al

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ma appearing as a solitary lung mass without any other accom-panying radiologic findings (e.g. pneumothorax, hemothorax or cavity formation) or clinical manifestations has not been re-ported previously as an initial manifestation of vEDS. It may have been caused by silent laceration of the lung parenchyma which formed a chronic organized hematoma that mimicked a solitary pulmonary mass.

Because vEDS has the worst prognosis of all types of EDS, bio-chemical confirmation is necessary to establish the diagnosis. Di-agnosis is made by demonstration of structurally abnormal colla-gen III or direct mutation analysis (1-6). Patients with this type of EDS should avoid heavy physical exercise and playing musical instruments, all of which could increase intrathoracic pressure (9). Coughing and constipation should be prevented since the fragile intestinal walls can cause a high recurrence rate of colon perforation (10). Pregnancy should be closely monitored due to an increased risk of death from uterine rupture (5).

There are some controversies regarding the therapeutic op-tions for vEDS, due to a broad spectrum of disease manifesta-tions. Conservative management with regulation of blood pres-sure is the treatment traditionally recommended for vEDS patients with asymptomatic complications. Patients with frank bleeding require emergent operative repair or catheter-directed embolization (11). Currently, there is no effective method to prevent the complications associated with vEDS. Further stud-ies are required to determine how to prevent these complica-tions using gene therapy (1).

We had made two mistakes during the process of diagnosis and treatment of the present case. First, we should have consid-ered a follow up image study with conservative treatment or CT guided transthoracic needle biopsy instead of surgical re-moval since the first impression of the solitary mass was of a benign nature and the first excisional operation may have influ-enced all the sequential hemorrhagic events or accelerated the complications. Second, after excision of the mass, the specimen showed only an old hemorrhage with fibrotic tissue. At that time, we should have evaluated the cause of hemorrhage through a ge-netic study, and determine the treatment plan with consider-ation of the background connective tissue disorder.

In summary, we report here a rare case of vEDS with a unique initial presentation of an isolated pulmonary hematoma. Al-though the diagnosis of vEDS depends on pathologic and ge-

ment for about 1 month, the patient was discharged from the hospital. On serial follow-up chest radiography, the size of the hematoma was decreased but not completely resolved. Also, re-petitive pneumothorax and other small hematomas developed. Currently, the patient is under close observation with his blood pressure under control at the cardiovascular department of our hospital.

DISCUSSION

EDS is an uncommon inherited disorder characterized by abnormalities in the components of the extracellular matrix such as collagen, which cause hyperextensibility of the skin, hy-permobility of large joints and easy bruising (1). The frequency of this syndrome is reported to be 1 in 10000 (2). EDS was clas-sified into the following six types in a conference at Ville-franche in 1997, drawing upon the accumulated clinical experi-ence and advances in molecular genetics: the classic type, the hypermobility type, the vascular type, the kyphoscoliosis type, the arthrochalasia type and the dermatosparaxis type (3).

The vEDS is an autosomal dominant inherited disease caused by a single allele mutation in the COL3A1 gene coding for type III collagen, which results in qualitative or quantitative abnormalities of mature type III collagen protein (1). The vEDS accounts for less than 4% of all EDS patients and has the worst prognosis (4). The most common initial complications in vEDS patients are arterial dissection or rupture and gastrointestinal rupture; these initial complications rarely develop in other organs (5). In vEDS patients, skin hyperextensibility and joint hypermo-bility are uncommon findings, which make vEDS different from the other types of EDS (1). The vEDS patients demonstrate ec-chymosis, translucent skin and a distinctive facial appearance with prominent eyes, a thin pinched nose, small lips, hollow cheeks, and lobeless ears (2).

The most common respiratory complication of vEDS is spontaneous pneumothorax. Since type III collagen is synthe-sized not only in the vessel walls but also by fibroblasts within the lung parenchyma, tears in the lung parenchyma are not un-common in these patients (6). Additionally reported findings include hemothorax due to ruptured thoracic arteries, thick-walled cavities, bullous lung disease and bronchiectasis (7, 8). To the best of our knowledge, an isolated pulmonary hemato-

Vascular Ehlers-Danlos Syndrome

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the vascular type. N Engl J Med 2000;342:673-680

6. Selim B, Lane CR, Rubinowitz AN, Siner JM. Spontaneous

hemothorax and recurrent hemoptysis in a 26-year-old

man with skin lesions. Chest 2010;137:480-483

7. Herman TE, McAlister WH. Cavitary pulmonary lesions in

type IV Ehlers-Danlos syndrome. Pediatr Radiol 1994;24:

263-265

8. Ishiguro T, Takayanagi N, Kawabata Y, Matsushima H, Yo-

shii Y, Harasawa K, et al. Ehlers-Danlos syndrome with re-

current spontaneous pneumothoraces and cavitary lesion

on chest X-ray as the initial complications. Intern Med

2009;48:717-722

9. Dimsdale JE, Nelesen RA. French-horn hypertension. N

Engl J Med 1995;333:326-327

10. Sykes EM Jr. Colon perforation in Ehlers-Danlos syndrome.

Report of two cases and review of the literature. Am J

Surg 1984;147:410-413

11. Oderich GS, Panneton JM, Bower TC, Lindor NM, Cherry

KJ, Noel AA, et al. The spectrum, management and clinical

outcome of Ehlers-Danlos syndrome type IV: a 30-year

experience. J Vasc Surg 2005;42:98-106

netic studies, vEDS should be suspected in cases of pulmonary hematoma or repetitive pneumothorax and hemorrhage of un-known origin.

REFERENCES

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582-590

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strup RJ. Ehlers-Danlos syndromes: revised nosology, Ville-

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and Ehlers-Danlos Support Group (UK). Am J Med Genet

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4. Germain DP. Clinical and genetic features of vascular

Ehlers-Danlos syndrome. Ann Vasc Surg 2002;16:391-397

5. Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical

and genetic features of Ehlers-Danlos syndrome type IV,

폐종양으로 오인된 폐혈종이 초기소견으로 발현된 혈관성 엘러스-단로스 증후군1

강은주1 · 이기남1 · 최필조2 · 기창석3

혈관성 엘러스-단로스 증후군은 드문 유전질환으로 3형 교원질의 이상이 특징이며 주로 동맥박리와 파열로 나타난다. 저

자들은 18세 남자에서 폐종양으로 오인된 고립된 폐혈종이 초기소견인 혈관성 엘러스-단로스 증후군을 보고한다. 종양

의 수술적 제거 이후에 15개월 동안 기흉과 혈흉이 반복적으로 나타났고 좌상엽 및 좌하엽절제술과 흉강절개술을 다수

시행하여 치료하였다. 병리학적 유전학적 검사를 통해 혈관성 엘러스-단로스 증후군으로 진단되었다.

동아대학교 의과대학 동아대학교의료원 1영상의학과, 2흉부외과, 3성균관대학교 의과대학 삼성의료원 진단검사의학과