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1 ISSN: (Print)/ (Online) Tuberc Respir Dis 2012;72:50-54 CopyrightC2012. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved. 자발성혈흉으로내원하여진단된유전출혈모세혈관확장증 1 예 Case Report 연세대학교원주의과대학 1 내과학교실, 2 흉부외과학교실, 3 영상의학교실, 4 병리학교실김종환 1, 박일환 2, 권우철 3, 김영주 3, 정순희 4, 이선녕 1, 이석정 1, 이지호 1, 정세현 1, 정예령 1, 김상하 1 A Case of Hereditary Hemorrhagic Telangiectasia Diagnosed through Spontaneous Hemothorax Chong Whan Kim, M.D. 1, Il Hwan Park, M.D. 2, Woocheol Kwon, M.D. 3, Young Joo Kim, M.D. 3, Soon Hee Jung, M.D. 4, Shun Nyung Lee, M.D. 1, Seok Jeong Lee, M.D. 1, Ji-Ho Lee, M.D. 1, Saehyun Jung, M.D. 1, Ye-Ryung Jung, M.D. 1, Sang-Ha Kim, M.D. 1 Departments of 1 Internal Medicine, 2 Thoracic Surgery, 3 Radiology, and 4 Pathology, Yonsei University Wonju College of Medicine, Wonju, Korea Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare autosomal dominant disease characterized by heterogenous multisystemic dysplasia of the vascular tissue. Prevalence of HHT is 1 in 5,000 8,000. HHT commonly presents with recurrent epistaxis, but may have more serious consequences if visceral vascular beds are involved. Approximately 30 50% of HHT cases also present with pulmonary arteriovenous malformation (PAVM). Spontaneous hemothorax is less common, and PAVM is one of the causes leading to hemothorax. Our case involved an 18-year-old female who had suddenly developed right chest pain. The reason for chest pain was due to right spontaneous hemothorax accompanied by PAVM in the right middle lobe. The patient was additionally diagnosed with HHT upon examination of her family history, specifically through her mother's symptom that included recurrent epistaxis and mucosal telangiectasia. Key Words: Telangiectasia, Hereditary Hemorrhagic; Hemothorax; Arteriovenous Malformations 서 대부분의혈흉은외상이나시술등에의해발생되며자발성혈흉은흔하지않은것으로알려져있다 1. Osler- Weber-Rendu disease라고도알려져있는유전출혈모세혈관확장증 (hereditary hemorrhagic telangiectasia) 은자발성혈흉을동반할수있는질환으로전신적인혈관조직의형성이상을특징으로하는상염색체우성질환이다. 발생빈도는프랑스, 덴마크, 일본등의지역에서보고된 Address for correspondence: Sang-Ha Kim, M.D. Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162, Ilsan-dong, Wonju , Korea Phone: , 0926, Fax: sanghakim@yonsei.ac.kr Received: Sep. 16, 2011 Revised: Oct. 10, 2011 Accepted: Dec. 2, 2011 론 바에의하면약 5,000 8,000명당 1명정도로발생한다 2. 이질환은자발적이고반복적인비출혈, 피부점막에서관찰되는모세혈관확장증, 내장부위의동정맥기형, 가족력등을특징으로한다 3. 유전출혈모세혈관확장증환자의약 30 50% 는폐에동정맥기형이동반되며오랜기간동안무증상으로존재할수있으나생명을위협하는출혈이발생하는경우도있으며여자환자의경우임신기간동안에파열의위험이높아진다 4. 저자들은특별한과거력이나외상력이없는 18세여자환자가자발성혈흉이관찰되어원인을찾던중유전출혈모세혈관확장증을진단한증례를경험하였기에문헌고찰과함께보고하는바이다. 증례환자 : 최, 18세, 여자 50

Tuberculosis and Respiratory Diseases Vol. 72. No. 1, Jan. 2012 주소 : 내원당일발생한우측흉벽통증과거력 : 특별한과거력은없었으며, 내원전외상력도없었다.

의식은명료하였고급성병색소견을보였으며결막은창백하지않았고생리기간은아니었다. 호흡곤란은없었으며청색증이나곤봉지등은관찰되지않았고, 심잡음은없었다. 청진에서우측폐야에거친수포음이들렸으며, 우측하폐야의호흡음은감소되었다. 구강점막을확인하였을때혀 끝에다발성모세혈관확장증이관찰되었다 (Figure 1B).

6 mg/dl, AST 14 U/L, ALT 9 U/L, 총빌리루빈 0.5 mg/dl, LDH 211 U/L, 프로트롬빈시간 10.9 초로정상이었다. 진단적흉수천자를시행하여확인한흉수검사에서혈성흉수였으며, 총단백 6.8 g/dl, LDH 231 U/L로삼출성이었고, 헤마토크리트 26.

Mother (A) and daughter (B) had multiple telangiectasia on the mucosa of their tongues and lips. Figure 2. (A) 2.

2 Tuberculosis and Respiratory Diseases Vol. 72. No. 1, Jan 주소 : 내원당일발생한우측흉벽통증과거력 : 특별한과거력은없었으며, 내원전외상력도없었다. 가족력 : 어머니가잦은비출혈이있었고구강점막과입술, 혀에다발성모세혈관확장증이관찰되었다 (Figure 1A). 진찰소견 : 내원당시혈압은 124/70 mm Hg, 맥박은 61회 / 분, 호흡수는 20회 / 분, 체온은 36.0 o C였다. 의식은명료하였고급성병색소견을보였으며결막은창백하지않았고생리기간은아니었다. 호흡곤란은없었으며청색증이나곤봉지등은관찰되지않았고, 심잡음은없었다. 청진에서우측폐야에거친수포음이들렸으며, 우측하폐야의호흡음은감소되었다. 구강점막을확인하였을때혀 끝에다발성모세혈관확장증이관찰되었다 (Figure 1B). 검사실소견 : 말초혈액검사에서백혈구 /L, 혈색소 11.1 g/dl, 헤마토크리트 34.5%, 혈소판 /L이었다. 생화학검사에서총단백 6.4 g/dl, 알부민 4.0 g/dl, BUN 13 mg/dl, 크레아티닌 0.6 mg/dl, AST 14 U/L, ALT 9 U/L, 총빌리루빈 0.5 mg/dl, LDH 211 U/L, 프로트롬빈시간 10.9 초로정상이었다. 진단적흉수천자를시행하여확인한흉수검사에서혈성흉수였으며, 총단백 6.8 g/dl, LDH 231 U/L로삼출성이었고, 헤마토크리트 26.7% 로혈흉을진단하였다. 소변 hcg 및적혈구는음성이었다. 혀점막이외의다른장기의점막에서모세혈관확장증을확인하기위해위식도내시경검사및비 Figure 1. Mother (A) and daughter (B) had multiple telangiectasia on the mucosa of their tongues and lips. Figure 2. (A) 2.5 cm nidus formation with dilatation of segmental pulmonary artery and vein suggesting pulmonary arteriovenous malformation in the right medial segment. (B) Pulmonary AVM was in broad contact with the right major fissure in the lung window setting of the chest CT. (C) Axial image of contrast-enhanced chest CT showed cm enhancing mass with calcification in the prevascular space. The right hemothorax is shown here. CT: computed tomography. 51

CW Kim et al: Hereditary hemorrhagic telangiectasia through spontaneous hemothorax Figure 3.

Figure 4. (A) A well encapsulated white gray mass (6.0 5.5 1.6 cm) with homogenous cut surface, lobulated by fibrous septa, was present.

경검사를시행하였으나이상소견은없었다. 방사선소견 : 흉부엑스선사진에서우측흉수가의심되었으며흉부컴퓨터단층촬영을시행하였을때, 우측흉수와함께우중엽에폐동정맥기형이의심되는소견 (Figure 2A) 이관찰되었고위치는대엽간열에접해있었다 (Figure 2B).

뇌컴퓨터단층촬영을시행하였을때특별히관찰되는이상소견은없었다. 치료 : 흉수는흉강삽관술을시행하여 20일동안총 1,091 ml가배액되었다. 우중엽의폐동정맥기형은혈관조영술에서출혈소견이관찰되지는않았으나출혈의예방을위해코일색전술을시행하였다 (Figure 3B).

3 CW Kim et al: Hereditary hemorrhagic telangiectasia through spontaneous hemothorax Figure 3. Pulmonary angiography revealed pulmonary arteriovenous malformation in the right middle lobe before (A) and after mechanical coil embolization (B). Figure 4. (A) A well encapsulated white gray mass ( cm) with homogenous cut surface, lobulated by fibrous septa, was present. (B) Type B1 thymoma was observed showing few thymic epithelial cells with rich non-neoplastic lymphocytes in the background (H&E stain, 200). 경검사를시행하였으나이상소견은없었다. 방사선소견 : 흉부엑스선사진에서우측흉수가의심되었으며흉부컴퓨터단층촬영을시행하였을때, 우측흉수와함께우중엽에폐동정맥기형이의심되는소견 (Figure 2A) 이관찰되었고위치는대엽간열에접해있었다 (Figure 2B). 또한, 우측앞종격동에 cm 크기의석회화를동반한비균일조영증강되는종양이관찰되었다 (Figure 2C). 혈흉의원인을확인하기위해기관지동맥및폐동맥혈관조영술을시행하였으며, 우중엽의병변은폐동정맥기형으로확인되었다 (Figure 3A). 뇌컴퓨터단층촬영을시행하였을때특별히관찰되는이상소견은없었다. 치료 : 흉수는흉강삽관술을시행하여 20일동안총 1,091 ml가배액되었다. 우중엽의폐동정맥기형은혈관조영술에서출혈소견이관찰되지는않았으나출혈의예방을위해코일색전술을시행하였다 (Figure 3B). 앞종격동종양은진단을위한비디오흉강경수술을통해흉선종으로확인되었고, 수술을통해완전제거되었으며폐동정맥기형도함께제거되었다. 조직학적소견 : 앞종격동종양은흉선종 B1형으로진단되었다 (Figure 4). 우중엽의폐동정맥기형은흉막에인접하여위치하였으며크기는 cm였고, 인접한흉막표면에는암갈색의색소침착이육안적으로관찰되었고모세혈관확장증도동반되어있었다 (Figure 5). 경과 : 수술적제거후에특별한증상없이외래에서추적관찰중이다. 52

Tuberculosis and Respiratory Diseases Vol. 72. No. 1, Jan. 2012 Figure 5. (A) Pulmonary arteriovenous malformation indicated an ill-defined hemorrhagic nodule (2.0 1.5 1.

고찰혈흉은흉수의헤마토크리트수치가혈액의헤마토크리트수치의 50% 를초과할때진단된다. 혈흉의원인은대부분흉수천자, 중심관삽입, 흉막생검등과같은시술이나흉부외상에의해발생한다. 자발성혈흉은흔하지않으며, 원인으로는혈관파열, 악성종양, 항응고제사용및혈액학적이상등이있다 1.

4 Tuberculosis and Respiratory Diseases Vol. 72. No. 1, Jan Figure 5. (A) Pulmonary arteriovenous malformation indicated an ill-defined hemorrhagic nodule ( cm) composed of dilated tortuous blood vessels with thin walls. (B) Pulmonary arteriovenous malformation demonstraated dilated vessels with an abnormal distribution (H&E stain, 20). 고찰혈흉은흉수의헤마토크리트수치가혈액의헤마토크리트수치의 50% 를초과할때진단된다. 혈흉의원인은대부분흉수천자, 중심관삽입, 흉막생검등과같은시술이나흉부외상에의해발생한다. 자발성혈흉은흔하지않으며, 원인으로는혈관파열, 악성종양, 항응고제사용및혈액학적이상등이있다 1. 그밖에혈흉과관련이있는혈관질환으로는대동맥박리또는파열, 폐혈관기형, 4형 Ehlers- Danlos 증후군, von Recklinghausen 병등이있다 1. 그러나, 폐동정맥기형을동반한유전출혈모세혈관확장환자에서혈흉이있었던증례보고는흔하지않다. 유전출혈모세혈관확장증은상염색체우성으로유전되어쉽게파열되는혈관벽이만들어지는질환으로, 1) 자발적이고반복적인비출혈, 2) 입술, 구강, 손가락, 코등의피부점막에서관찰되는모세혈관확장증, 3) 위장관, 폐, 간, 뇌및척수등의내장부위에존재하는동정맥기형, 4) 가족력중에서 3개이상이존재하면진단될수있다 3. 이질환은두가지다른유전자의돌연변이와연관이있으며, 이중 1형은폐와뇌에동정맥기형을잘동반한다 5. 폐동정맥기형을동반한유전출혈모세혈관확장환자에서동반되는흔한호흡기증상은운동시호흡곤란으로약 50% 의환자에서나타나며이는폐동정맥기형에서가장빈번하게발생하는증상이다. 그밖의증상으로곤봉지 (20%), 청색증 (18%), 객혈 (10%), 흉통 (6%) 등이있다 6. 흔하지않으나유전출혈모세혈관확장증환자에서폐동정맥기형으로인한출혈은심각한상황및사망을야기할수있으며, 한조사에의하면 143명의환자중 5명에서혈흉 이발생하였고 7, 다른조사에서는 126명의환자중 4명에서혈흉이발생하였다고한다 8. Ishikawa 등 4 은증례보고와함께 1975년부터 2008년까지문헌에보고된폐동정맥기형의파열로인한대량혈흉총 14예를분석하여보고하였다. 남자가 5명, 여자가 9명이었다. 총 14명증례에서유전출혈모세혈관확장증이동반되어폐동정맥기형의파열로인한혈흉이있었던경우는 9예 (64.3%) 였으며남자 3명, 여자 6명으로여자가더많았다. 이들의평균나이는 38.3±12.5세였고, 최소연령의환자는 21세였다. 이환자들의배액된대량혈흉의양은확인가능했던 7명에서평균 1,350±695 ml였다. 파열된폐동정맥기형의위치는우측폐가 3명, 좌측폐가 6명으로좌측폐가더많았다. 이전에보고되었던혈흉을동반한유전출혈모세혈관확장증증례들은환자의상황으로인해폐동정맥기형이확인되지못한예를제외하고는모든증례에서폐동정맥기형이동반되어있었다 4,7-9. 본증례는 18세여자환자로나이는보고된증례들보다는적은나이에진단이되었으며, 배액된혈흉의양은이전에보고된증례들과비슷한다량의혈흉양상이었으나폐동정맥기형의파열에대한증거는없어보였다. 그러나, 입원하여시행한검사에서혈흉을유발할수있는다른원인에대해고려할수있는소견은관찰되지않았으며, 폐동정맥기형은흉부컴퓨터단층촬영과조직학적소견에서모두흉막에인접한소견을보여자발성혈흉의원인일가능성이높을것으로판단된다. 폐동정맥기형이동반된유전출혈모세혈관확장증에서는출혈에의한합병증외에도우좌단락에의한패혈성색전이뇌혈류로유입되어뇌경색이나뇌농양을일으켜서나타나는신경학적징후들이발생할수있다. 뇌경색의 53

5 CW Kim et al: Hereditary hemorrhagic telangiectasia through spontaneous hemothorax 경우는폐동정맥기형이동반된환자에서 10 19% 정도가발생하고뇌농양의경우는 5 19% 정도가발생하기때문에합병증예방을위해폐동정맥기형의치료가필요하며 6, 폐동정맥기형의영양동맥의직경이 3 mm 이상이고, 다발성인경우합병증의위험이증가하여무증상이라도치료의적응증이된다 10. 폐동정맥기형의치료목적은중추신경계합병증을예방하고증상이발생하였을때이를호전시키기위한것으로색전술을시행하거나수술을통해제거한다 6,8. Pollak 등 9 은총 155명의폐동정맥기형환자에대해색전술을시행한후평균 3년동안의추적검사를통하여임상적인결과를확인하였으며 155 명의환자중유전출혈모세혈관확장증에의한경우는 148명 (95%) 이었다. 이연구에서증상을동반했던폐동정맥기형의경우는 53.5% 였고, 무증상이었으나영상검사에서양성소견을보인경우가 44.2% 였다. 증상을보인경우에는호흡곤란이가장많았으며, 뇌농양, 호흡곤란없는저산소혈증, 뇌졸중, 객혈, 발작순의증상들이었다. 대부분의원인은색전술을시행한잔여병변에서재관형성 (recanalization) 이나부영양동맥형성, 측부혈관에의한재관류등에의한경우이거나, 당시에는크기가작았던폐동정맥기형이커져서발생한경우였다. 따라서폐동정맥기형에대하여색전술을시행한후에도이와같은이상의확인을위한추적관찰이필요하다. 한편, Bevelaqua 등 11 은폐동정맥기형으로인한출혈환자의 30 50% 는임신과연관되어있다고보고하였으며, 혈액량과심박출량의증가로인해임신 2기와 3기에주로발생한다고하였다. 그러므로, 임신을계획하고있는여성에서는필요하다면폐동정맥기형의존재여부를확인하고치료하는것이필요하다. 본환자는가임기여성으로혈흉의원인이될수있는폐동정맥기형을비디오흉강경수술로완전제거하여향후폐동정맥기형으로인해발생할수있는출혈을포함한합병증이예방될수있을것으로기대된다. 저자들은자발성대량혈흉환자에서폐동정맥기형이동반된유전출혈모세혈관확장증을진단하였으며, 비디오흉강경수술을통해우연하게발견된흉선종과폐동정맥기형을완전절제하여보고하는바이다. 참고문헌 Spontaneous hemothorax: a comprehensive review. Chest 2008;134: Shovlin CL, Jackson JE. Pulmonary arteriovenous malformations and other vascular abnormalities. In: Mason RJ, Broaddus VC, Martin TR, King TE Jr, Schraufnagel DE, Murray JF, Nadel JA, editors. Murray & Nadel's textbook of respiratory medicine. 5th ed. Philadelphia: Saunders; p Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler- Weber syndrome). Am J Med Genet 2000;91: Ishikawa T, Pollak S, Pflugradt R, Bohnert M, Grosse Perdekamp M, Thierauf A, et al. Pulmonary arteriovenous malformation causing sudden death due to spontaneous hemothorax. Int J Legal Med 2010;124: Sabbà C, Pasculli G, Lenato GM, Suppressa P, Lastella P, Memeo M, et al. Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers. J Thromb Haemost 2007;5: Cottin V, Dupuis-Girod S, Lesca G, Cordier JF. Pulmonary vascular manifestations of hereditary hemorrhagic telangiectasia (rendu-osler disease). Respiration 2007; 74: Ference BA, Shannon TM, White RI Jr, Zawin M, Burdge CM. Life-threatening pulmonary hemorrhage with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia. Chest 1994;106: Cottin V, Chinet T, Lavolé A, Corre R, Marchand E, Reynaud-Gaubert M, et al. Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: a series of 126 patients. Medicine (Baltimore) 2007;86: Pollak JS, Saluja S, Thabet A, Henderson KJ, Denbow N, White RI Jr. Clinical and anatomic outcomes after embolotherapy of pulmonary arteriovenous malformations. J Vasc Interv Radiol 2006;17: Kim M, Song HY, Choi JK, Jeong H, Park IN, Choi SB, et al. A familial case of hereditary hemorrhagic telangiectasia. Tuberc Respir Dis 2009;66: Bevelaqua FA, Ordorica SA, Lefleur R, Young B. Osler-Weber-Rendu disease. Diagnosis and management of spontaneous hemothorax during pregnancy. N Y State J Med 1992;92: Ali HA, Lippmann M, Mundathaje U, Khaleeq G. 54

Trd022.hwp

Trd022.hwp 김신태, 이선녕, 이석정, 정필문, 박홍준, 신명상, 김종환, 이부길, 김상하, 리원연, 신계철, 용석중 Shin-Tae Kim, M.D., Shun Nyung Lee, M.D., Seok Jeong Lee, M.D., Pil Moon Jung, M.D., Hong Jun Park, M.D., Myung Sang Shin, M.D., Chong Whan Kim,