폐공동을형성한유육종증 1 예 단국대학교의과대학내과학교실, 방사선학교실 1, 해부병리학교실 2 이보한, 김명진, 김동우, 김정혁, 방기태, 이계영, 지영구, 박재석, 이인선 1, 권미선 2, 김윤섭 A Case of Sarcoidosis with Cavitation Bo Han Lee, M.D., Jin Myong Kim, M.D., Dong Woo Kim, M.D., Jung Hyuk Kim, M.D., Ki Tae Bang, M.D, Kye Young Lee, M.D., Young Koo Jee, M.D., Jae Seuk Kim, M.D., Youn Seup Kim, M.D., In Sun Lee, M.D. 1, Mi Seon Kwon, M.D. 2 Department of internal Medicine, Department of Radiology 1, Department of Pathology 2, Dan Kook University hospital, Chunan, Korea Sarcoidosis is a rare systemic disorder with unknown cause that is characterized pathologically by non-caseating granuloma. The lung and mediastinal lymph nodes are almost always involved, and most patients experience acute or insidious respiratory symptom. Because sarcoidosis is an interstitial lung disorder involving the alveoli and bronchioles, the most common radiological finding is a reticularnodular lesion with lymphatic distribution. However, cavitation is quite rare. Sarcoidosis is also a major cause of hepatic granuloma in Western countries, accounting for 12% to 30% of cases. In most patients, the course of hepatic sarcoidosis is benign. However, chronic intrahepatic cholestasis or portal hypertension may develop in some patients. We report a case of sarcoidosis with cavitation and hepatic involvement. (Tuberc Respir Dis 2005; 59: 546-550) Key words : Sarcoidosis, Cavity, Hepatic granuloma 서 유육종증은원인불명의전신성육아선종으로흉부내장기즉폐문임파선과폐를가장흔하게침범하며그외말초임파선, 피부, 눈, 간, 비장등에침범한다. 우리나라에서는 2000년시행된제 2차전국실태조사결과인구 100,000명당 0.13 명정도의유병율을나타내고있다 1. 유육종환자의약 1/5-1/3에서내원시발열, 피로, 전신쇄약및체중감소등의전신증상을호소하고침범된장기에따라증상이나타나지만제일많은것은역시호흡기증상이다. 흉부 X-선상폐침윤의소견으로는망상결절성음영, 섬세한선형음영등의간질성음영이주로나타난다. 유육종증이폐를침범하여공동을형성하는것 론 Address for correspondence : Youn Seup Kim, M.D. Department of Internal Medicine, College of Medicine, Dankook University, San29, Anseo-dong, Chonan, Choong Nam, 330-714, Korea Phone : 041-550-3911 Fax : 041-556-3256 E-mail : drys99@dankook.ac.kr Received : Jul. 28. 2005 Accepted : Sep. 20. 2005 은드문것으로알려져있다. 국내의경우 2예이외에는보고된것이없고본증례의경우간과비장의이상소견도함께보여문헌고찰과함께보고하는바이다. 증례 32세여자가 3개월전부터계속된기침과호흡곤란을주소로 2003년 10월내원하였다. 과거력상 2001년 3월기침과발열을주소로결핵으로진단받고항결핵제를 3개월복용하였으나증상호전없던중 2001년 6 월목과서혜부주위에 1-1.5cm 정도의다발성림프절종대가발생하여내원하였다. 당시검사실소견은말초혈액검사상백혈구 3850/mm 3 ( 중성구 :64%, 림프구 :19%, 단핵구 :5%), 혈색소 9.2 g/dl, 헤마토크릿 29.9%, 혈소판 224K/mm 3, 적혈구침강계수는 35mmol/ hr 였으며, protein 6.7 g/dl, albumin 3.2 g/dl, AST 17 IU/L, ALT 32 IU/L, bilirubin 0.24 mg/dl 였고, ALP는 61 IU/L 였다. 혈청안지오텐신전환효소는 28 U/L( 정상 12-35 U/L) 로정상이였다. 흉부 X-선상양폐야에망상결절형침윤을보였고흉부고해상도단층촬영상간질성침윤과소결절이관찰되었다 546
Tuberculosis and Respiratory Diseases Vol. 59. No. 5, Nov. 2005 (Fig. 1). 기관지내시경검사는특별한병변없었으나서혜부림프절생검에서비건락성육아종소견 (Fig. 2) 보였고호흡기증상지속되어유육종증으로진단후 2001년 9월까지스테로이드치료하였고 2003년 4월까지외래에서추적관찰하였다. 2003년 10월입원당시활력증후는혈압 110/80 mmhg, 맥박수 102회 / 분, 호흡수 20회 / 분, 체온은 38.5 였다. 두경부진찰상림프절의종대소견은보이지않았으나서혜부주위에는 0.5-1cm 정도의림프절이 3-4 개정도촉지되었다. 흉부진찰에서양쪽하부폐에서수포음이들렸으며복부진찰상간, 비장의종대가확인되었다. 입원당시검사실소견은말초혈액검사상백혈구 10410/mm 3 ( 중성구 :86%, 림프구 :6.6%, 단핵구 :7%), 혈색소 9.3 g/dl, 헤마토크릿 29.6%, 혈소판 221K/mm 3, 적혈구침강계수는 73 mmol/hr 였으며, 동맥혈가스분석은 ph 7.416, PO 2 79.5 mmhg, PCO 2 39.7 mmhg, HCO 3 25.0 mmol/l, calcium 9.0 mg/dl, BUN 8.7 mg/dl, Cr 0.73 mg/dl, protein 7.6 g/dl, albumin 3.3 g/dl, AST 216 IU/L, ALT 252 IU/L, bilirubin 0.51 mg/dl 였고, ALP는 304 IU/L, γ-gt 233 IU/L 였다. 객담결핵균도말검사와배양검사는음성이며객담도말검사에서는특이소견없었으며진균도발견되지않았다. 폐기능검사는 FVC 2.0L( 예즉치의 62.5%), FEV 1 Figure 1. Initial scan Chest PA shows bilateral, patchy area of consolidation and coarse reticulonodular opacities involving mainly the perihilar regions of the both lungs. There is widening of right paratracheal stripe, suggesting lymphadenopathy. Chest HRCT scan shows numerous nodules in relation to the parahilar, bronchovascular interstitium and a mass-like opacity in left parahilar lung. Bronchovascular bundles are irregularly thickened. Subpleural nodules (arrows) are seen along the costal pleural surface. Figure 2. Numerous confluent noncaseating granulamas evenly placed in lymphoid parenchyma (A :*40, B :*400 by H&E stain) 547
BH Lee et al. : A case of sarcoidosis with cavitation 1.56L( 예측지의 56.3%), FEV 1 /FVC는 78.1%, DLCo 9.98ml/min/mmHg( 예측치의 39.5%) 으로제한성환기장애의양상을보이고있었다. 면역혈청검사상 antinuclear Ab와 rheumatoid factor는음성소견보였으며혈청안지오텐신전환효소는 95 U/L( 정상 12-35 U/L) 로증가되어있었다. 안저검사소견은정상이었다. 흉부 X-선검사사진상양폐야에망상결절형침윤과공동형성된소견을보였으며흉부고해상도단층촬영상양폐야에미만성간질성침윤과공동형병변이발견되었으며양쪽폐문임파절들이커져있었다 (Fig. 3 A,B). 컴퓨터단층촬영상간비장종대와 간과비장에다발성의작은저음영의결절소견 (Fig. 3C) 보였다. 그러나, 호흡곤란과전반적인상태가좋지않아기관지내시경검사와간조직생검은시행하지못하였다. 핵의학검사는 HBs Ag/Ab(-/-), HBe Ag/Ab(-/+), HAV Ab(IgM) (-), anti HCV Ab(-) 소견을보였다. 이상의검사결과로유육종증의재활성으로인한폐의공동형성과간의침범으로진단하였다. 환자는스테로이드 1 mg/kg/day 로투여후수일후부터기침과호흡곤란증상은호전되었으며치료 1달후간효소수치는정상으로돌아왔다. 스테로이드를점차감량하여 1년사용후추적검사한흉부고해상도단층 (C) Figure 3. Follow up Chest PA shows bilateral thin walled cavities (open arrows) within consolidation and coarse reticulonodular opacities in perihilar region. On chest HRCT, cavities (open arrows) are seen within consolidation in both parahilar lung. Nodular and irregular thickening of bronchovascular and interlobular septum (arrows) has been aggravated. CT scan at the level of upper abdomen shows hepatosplenomegaly and disseminated tiny low density nodules in liver and spleen (C). Figure 4. Follow-up, after steroid Tx. On follow-up chest PA after steroid treatment, cavities and consolidation in both parahilar lungs have been decreased in size and extent. Also, coarse reticulonodular opacities in both parahilar lungs have been decreased in extent. On CT scan at the level of upper abdomen, disseminated tiny low density nodules in liver and spleen have been gone. 548
Tuberculosis and Respiratory Diseases Vol. 59. No. 5, Nov. 2005 촬영과흉부 X-선에서공동의감소와미만성간질성침윤소견의호전을보였으며간과비장의종대가감소되고다발성의저음영결절소견도거의사라졌다 (Fig. 4). 고찰유육종증은비건락성육아종을특징으로하는원인불명의질환으로, 무증상에서부터진행성다발성장기부전 (multiple organ failure) 까지나타날수있으며, 경과는저절로호전되기도하고만성화소견을보이기도한다. 우리나라에서는 1968년첫증례가보고된후 2000 년시행된전국실태보고조사결과유육종증의발생률이계속증가하는추세를보였으며발생률은인구 100,000명당 0.13 명으로조사되었다 1. 정확한병인에대해서는알려진것이없으며, 종종만성 beryllilosis, 과민성폐장염, 결핵, 진균감염등의다른육아종성질환과혼동되는경우가있다. 유육종증의임상증상은침범장기에따라매우다양하며, 폐침범에의한전형적증상으로는운동시호흡곤란과건성기침이있다. 유육종증환자의 90% 에서병의경과중폐의침범이발생하는데이중양측대칭성의폐문임파절비대나기관주위의임파절비대는폐유육종증의전형적인소견으로알려져있다 2. 유육종증이폐실질을침범한경우흉부촬영상섬유화를제외한폐병변은크게망상결절음영, 폐포성음영, 대결절로나눌수있다. 망상결절음영은폐병변의 75-90% 를차지하는가장흔한소견으로 3-5 mm 정도의소결절로구성된다 3,4. Nester 등에의한폐유육종증의 CT 소견에대한분석에서폐실질의유육종증은전형적으로 bronchov ascular bundle을따라소결절과불규칙한선상침윤으로나타났다. 폐유육종증의흉부방사선소견중공동형폐실질병변은드물게발생할수있는데, 외부적요인없이일차적으로육아종내의무혈성괴사에의해발생할수있고유육종증에서세균이나결핵균또는진균감 염과연관되어공동이발생할수있다. 본증례의경우유육종증진단후외래추적관찰중호흡곤란과기침을주소로입원시단순흉부촬영상공동소견보였고결핵균도말검사와배양검사상음성이였으며객담도말검사상특이소견없었고스테로이드치료중에공동이감소되는소견보여유육종증에의한일차적인공동형성으로진단하였다. 공동은저절로소실되거나그렇지않은경우도대부분은부신피질호르몬의사용으로호전되어공동이소실되거나공동벽의두께가감소된다 1. 본증례와같이유육종증은간을침범할수있는데유육종증은서양에서간육아종증 (hepatic granuloma) 의 12-30% 를나타내는주요원인이다 12. 유육종증환자의 40-70% 에서간조직생검상육아종성침윤을관찰할수있다. 대부분의환자에서는무증상이며심각한간기능장애는드물지만소수에서는만성간내담즙분비정지 (chronic intrahepatic cholestasis) 나문맥압항진증이유발될수있다 19. 그러나폐유육종증의폐병기와간침범의빈도는상관관계를보이지않는다 14. 비록유육종증의일차적인간침윤 (primary hepatic involvement) 이스테로이드치료의적응증이되지는못하나 1 과거간을침범한유육종증의증례보고에서는 (PATEL 에의해 ) 스테로이드치료후증상이없어지고간기능검사상이상소견이정상으로돌아오는소견을보였다. 본증례에서는비록환자의호흡곤란과전신허약감으로인해간조직생검은시행하지못했으나간염바이러스표지자가음성이고스테로이드치료후간기능수치가정상으로회복되었고간비장비대가줄어들었으며다발성의저음영침윤이호전되는양상을보였기에유육종증의간침범을생각할수있다. 치료에대해서는확실한지침이없으나전체적으로예후는좋은편이다. 초기에는자연치유를기대하여치료없이관찰하는것으로알려져왔으나, 최근들어중증의안구, 신경계또는심장을침범한유육종증, 중증의고칼슘혈중, 진행성 2기의폐질환, 증상이있는 2기의폐질환 549
BH Lee et al. : A case of sarcoidosis with cavitation 그리고 3기의폐질환등에서경구스테로이드제재나 methothrexate 가사용되기도하나정확한용량이나기간에대해서는확립된것이없다. 결 유육종증은여러장기를침범하는질환이나 90% 에서는병의경과중폐의침범이발생한다. 양측대칭성의폐문임파절비대나기관주위의임파절비대가전형적인소견이며공동의형성은매우드문것으로되어있다. 유육종증에의한공동의형성은공동을형성할수있는감염이나악성종양등을배제한후진단할수있으며저절로소실되거나스테로이드에반응을잘하는것으로알려져있다. 론 참고문헌 1. Kim DS, Ahn JJ. Sarcoidosis in Korea. Tuberc Respir Dis 2000;49:274-80. 2. Fanburg BL, Lazarus DS. Chapter 61. Sarcoidosis. In: Murray JF, Nadel JA, editors. Respiratory medicine. 2nd ed. Sauders; 1994. p. 1873. 3. Armstrong P, Wilson AG, Dee P, Hansell DM. Imaging of disease of chest. 2nd. St. Louis: Mosby; 1995. p. 568-85. 4. Muller NL, Kullnig P, Miller RR. The CT finding of pulmonary sarcoidosis: analysis of 25 Patients. AJR Am J Roentgenol 1989;152:1179-82. 4. Kim Y, Lee KS, Yoo JH, Rhee C, Chung EC, Kim SJ. Radiologic finding of pulmonary sarcoidosis: comparison between radiologic and HRCT. J Korean Radiol Soc 1998;39:73-80. 5. Muller NL, Kullnig P, Miller RR. The CT finding of pulmonary sarcoidosis: analysis of 25 patients, AJR Am J Roentgenol 1989;152:1179-82. 6. Ju MS, Lee HK, Chang JH, Cheon SH, Kim YK, Yoon HS, et al. A case of sarcoidosis with cavitary nodule of the lung. Tuberc Respir Dis 1998;45:1098-102. 7. Brauner MW, Grenier P, Mompoint D, Lenoir S, de Cremoux H. Pulmonary sarcoidosis: evaluation with high-resolution CT. Radiology 1989;172:467-71. 8. Rohatgi PK, Schwab LE. Primary acute pulmonary cavitation in sarcoidosis. AJR Am J Roentgenol 1980: 134:1199-203. 9. Tellis CJ, Putnam JS. Cavitation in large multinodular pulmonary disease: a rare manifestation of sarcoidosis. Chest 1977;71:792-3. 10. Rockoff SD, Rohatgi PK. Unusual manifestation of thoracic sarcoidosis. AJR Am J Roentgenol 1985;144: 513-28. 11. Asai Y, Nakayama T, Furuichi S, Kobayashi T, Ha shimoto S, Horie T. Three cases of primary acute pulmonary cavitation in sarcoidosis. Nihon Kokyuki Gakkai Zasshi 2000;38:952-7. 12. Valla D, Pesseiguero-Mirinda H, Degott C, Lebrec D, Rueff B, Benhamou JP. Hepatic sarcoidosis with portal hypertension: a report of seven cases with a review of the literature. Q J Med 1987;63:531-44. 13. James DG, Sherlock S. Sarcoidosis of the liver. Sa rcoidosis 1994;11:2-6. 14. Folz SZ, Johnson CD, Swensen SJ. Abdominal mani festation of sarcoidosis in CT studies. J Comput Assist Tomogr 1995;19:573-9. 15. Ishak KG. Sarcoidosis of the liver and bile ducts. Mayo Clin Proc 1998;73:467-72. 550