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1 크론씨병에동반된 Goodpasture 증후군 1 예 순천향대학교의과대학내과학교실, 1 진단방사선과교실, 2 병리학교실김지연, 배준용, 정은정, 김양기, 이영목, 김기업, 어수택, 황정화 1, 진소영 2, 이동화 2 A Case of Goodpasture's Syndrome Combined with Crohn s Disease Ji-Yon Kim, M.D., Jun-Yong Bae, M.D., Eun-Jung Jung, M.D., Yang-Ki Kim, M.D., Young Mok Lee, M.D., Ki-Up Kim, M.D., Soo-taek Uh, M.D., Jung-Hwa Hwang, M.D. 1, So-Young Jin, M.D. 2, Dong-Wha Lee, M.D. 2 Division of Respiratory &Allergy Medicine, Department of Internal Medicine, Department of Radiology 1 and Department of Clinical Pathology 2, Soonchunhyang University, School of Medicine, Seoul, Korea A 29-year-old male patient was admitted due to his general weakness and poor oral intake for several months. He was diagnosed as having Crohn disease 16 years ago and total colectomy was performed 10 years ago. On the 3rd day after admission, gross hematuria and sudden hemoptysis combined with diffuse infiltration were noted on chest X-ray. His symptoms and the diffusely increased lung opacities improved with administering high-dose steroid therapy. Later, anti-gbm antibody was found to be positive on the laboratory findings. We report here on a rare case of Goodpsture syndrome combined with prolonged Crohn disease along with a review of literature. (Tuberc Respir Dis 2006; 61: ) Key word: Goodpsture syndrome, Crohn disease, anti-gbm antibody 서 론 중발생된 Goodpasture 증후군 1예를문헌고찰과함께보고하는바이다. Goodpasture 증후군은원인불명의병인을가진드문질환으로전형적으로젊은남자에서주로일어나며, 혈뇨와신증후군이하의단백뇨를보이는사구체신염, 폐출혈및항사구체기저막항체양성소견을보이는임상증후군이다. Goodpasture 증후군은급속히진행하는질환으로조기에진단을하여조기에치료방법을결정하는것이질병의예후와큰연관성을가진다. 크론씨병을포함하는염증성장질환에서보이는폐질환의임상증상은여러형태로나타날수있다. 크론씨병과 Goodpasture 증후군이어떠한연관성이있는지는현재까지알려져있지않지만, 크론씨병에서실제로혈관염에의한폐합병증을보이는경우는드문것으로알려져있다. 이에저자는국내에는아직보고가없는크론씨병의진단및장기간의치료 Address for correspondence : Soo-taek Uh, M.D. Department of Internal Medicine, Soonchunhyang University, School of Medicine, 657, Hannam-Dong, Yougsan-Ku, Seoul , Korea Phone: , Fax: uhs@hosp.sch.ac.kr Received : May Accepted : Aug 증례환자 : 29세남자, 성 주소 : 전신쇠약감현병력 : 29세남자가수개월간지속된전신쇠약감및식욕부진을주소로내원하였다. 과거력 : 환자는 16년전본원에서항문누공과농양으로크론씨병을진단받고, 항문주위농양에대한수술을 3차례시행하였고, 10년전전대장절제술을시행하였다. 20년전우상엽의폐결핵을진단받고 6개월간항결핵치료후완치받았으며, 17년전장결핵의심하에 3개월간항결핵치료를받는도중크론씨병을진단받고투약을중단하였다 (Figure 1, 2). 진찰소견 : 생징후는혈압 100/60 mmhg, 맥박 80 회 /min, 호흡수 18 회 /min, 체온 36.6 로보였으며, 매우흥분된모습을보였고안면은창백하였다. 육안적혈뇨와청진에서양측폐야에서라음이들렸다. 검사실소견 : 일반혈액검사에서백혈구 /mm 3, 혈색소 1.2 g/dl, 헤마토크릿 3.9%, 혈소판 /mm 3, 대개중동맥혈가스검사결과 ph 7.544, 384

Tuberculosis and Respiratory Diseases Vol. 61. No.4, Oct. 2006 Figure 1. Surgical specimen of intestine.

Lymphoid hyperplasia and multiple non-caseating granulomas are shown. PCO 2 29.5 mmhg, PO 2 75.0 mmhg, HCO 3 24.8 mmol/l, 일반화학검사에서 BUN/Cr 63/2.0 mg/dl, AST/ALT 126/98 U/L, Na/K/Cl 135/4.

2 Tuberculosis and Respiratory Diseases Vol. 61. No.4, Oct Figure 1. Surgical specimen of intestine. Multiple cobble stone and longitudinal ulcers are noted, and also skip areas locate between ulcer (arrow). Figure 2. Histologic finding of intestine. Lymphoid hyperplasia and multiple non-caseating granulomas are shown. PCO mmhg, PO mmhg, HCO mmol/l, 일반화학검사에서 BUN/Cr 63/2.0 mg/dl, AST/ALT 126/98 U/L, Na/K/Cl 135/4.4/102 mmol/ L, 일반요검사에서적혈구 many/hpf( 비정형적혈구 40%), 백혈구 5-9/HPF, 요단백 3+, 24시간요검사에서전체부피 1150 ml/day, Urea nitrogen 1.5 g/day, Creatinine 0.2 g/day, 총단백 625 mg/day, 혈액응고검사에서 PT/aPTT 14.2 sec/80.5%(inr 1.23) 로측정되었다. 환자의객담배양, 결핵균도말및배양에서특이소견이없었으며, 검사실소견에서는항사구체기저막항체가양성이었다. 자가면역질환감별을위해시행한항핵항체 (ANA:anti-nuclear antibody) 및류마티스인자 (RF:rheumatoid antibody) 는음성이었으며, 항호중구세포질항체 (ANCA: antineutrophilic cytoplasmic antibody) 는양성이었다. 또한단 순흉부촬영에서양측하폐야로음영의증가와흉수가관찰되었다. 치료및임상경과 : 내원 1일째농축적혈구 2 pint, 2일째농축적혈구 2 pint, 3일째농축적혈구 3 pint 투여하여혈색소 9.5 g/dl, 헤마토크릿 26.9% 로상승하였다. 내원 2일째시행한심초음파에서박출계수 (ejection fraction) 32% 및 4방의확장, 특히좌심실확장소견보였으며, 수혈과관련된급성폐손상 (transfusion related acute lung injury) 으로생각되어보존적치료를하였다. 환자는내원 3일째부터선홍색객혈을보였으며심한호흡곤란을호소하고흥분된모습을보여인공호흡기를사용하여보존적치료를하였으나, 지속적인혈뇨와객혈이있어항사구체기저막항체검사를시행하였다. 내원 7일째다시다량의객혈을보였고심한호흡곤란을호소하며단순흉 385

SM Park et al: A Case of Goodpsture Syndrome combined with Crohn Disease Figure 3. Serial follow up of chest X-ray. A: At admission, diffuse hazy infiltration was noted on right lung field.

3 SM Park et al: A Case of Goodpsture Syndrome combined with Crohn Disease Figure 3. Serial follow up of chest X-ray. A: At admission, diffuse hazy infiltration was noted on right lung field. B: Two days after admission, more aggravated and newly developed haziness wereas noted on right and left lung fields, respectively. C: Seven days after admission, increased haziness wereas still noted on both lung fields. D: 18 days after admission, haziness slightly improved with steroid therapy. 부촬영에서양폐야의음영증가를보여기관지내시경을시행하였고, 기관지내병변은없이다량의혈액이관찰되었고좌상엽에서간헐적인출혈이관찰되었다. 내원 10일째부터는 kg당 10 mg의고용량 methylprednisolone을투여하였으며, 내원 12일째단순흉부촬영에서폐부종이호전되고호흡곤란이감소되어 methylprednisolone 의용량을점차줄여나갔고, 내원 15일째부터는간헐적인객혈을보이다가점차빈도가감소하여 methylprednisolone 투여 12일후에는객혈이관찰되지않아 methylprednisolone의용량을 kg당 0.5 mg까지감량하였다. 이후 10일경과후에다시객혈을보여 methylprednisolone 고용량치료를시행하여호전을보여 kg당 1 mg까지감량하였으나, 수일경과후원내폐렴이발생하여항생제치료에반응하지않고점차진행하여패혈증으로사망하였다 (Figure 3). 고찰 Goodpasture 증후군은폐출혈과증식성 (proliferative) 사구체신염을특징으로하는질환으로, 항사구체기저막항체의존재가밝혀짐으로써이를포함하여 3주징 (triad) 이진단의기초가되었으며 1, 자가면역질환의일종으로생각되고있다 대에호발하고남자에서여자보다 2배의발생률을보이며 3, 코카시안 (Caucasian) 에서는보고가많으나국내에서는현재까지 6예만보고되고있다. 또한염증성장질환과 Goodpasture 증후군이동반되어있는보고는전세계적으로, 궤양성대장염과동반되어있는 Goodpasture 증후군한예 4 및크론씨병의추적관찰중발생한 anti-gbm nephritis 한예 5 만이있을뿐이다. 그러나국내에서는이증례와같이크론씨병에동반된 Goodpasture 증후군은보고된바가없다. 386

4 Tuberculosis and Respiratory Diseases Vol. 61. No.4, Oct Goodpasture 증후군의진단은폐출혈과사구체신염및 90% 이상에서양성을보이는혈액이나신장및폐조직에서항사구체기저막항체 (anti-glomerular basement membrane antibody) 를증명해야한다. 따라서항사구체기저막항체를가려낼수있는특이도및민감도가동시에높은검사법이필수적인데수년전까지만해도신장조직검사를통해진단을내렸었으나최근연구에서순환항사구체기저막항체검사의민감도가 %, 특이도가 % 에이르는것으로보고되고있어 6, 미만성폐출혈과신부전이있는경우에는순환항사구체기저막항체가있는경우만으로도진단이가능하다. 본환자의경우신장조직검사는시행하지못하였으나객혈, 혈뇨, 폐침윤등의임상소견및순환항사구체기저막항체양성소견을보여 Goodpasture 증후군으로진단이가능하였다. 원인불명의자가면역질환으로알려져있는염증성장질환에서장외임상증상을나타내는빈도는 21% 에서 41% 까지다양하게보고되고있으며, 신체어느곳이라도침범이가능하나폐및신장의침범은드물어전세계적으로폐의침범은 400예정도가보고되었다 7,8. 크론씨병에서장외증상이발현되는기전은순환면역복합체 (circulating immune complex) 및보체 (complement) 의침착에의한가설이있는데, 폐증상의발현에대해서정확한자가면역학적기전이밝혀지지는않았으나폐와장의태생학적기원이유사해서항원성을공유한다는공유항체가설 (shared antigen theory) 과 7, 사이토카인및장에서감작된림프구가다른장기점막에염증반응을일으켜폐증상이나타나는것으로추측하고있다 8. 이상과같이크론씨병과 Goodpasture 증후군모두가자가면역질환의연장선상에있다고하여두질환이같은스펙트럼의질환으로볼수는없으며, 그리고두질환이우연히발병했는지도현재로서는밝힐수없다. 따라서추후이러한증례가많아지게되면두질환의관계가정립되어질것으로생각된다. 간접면역형광법에의해서 ANCA를 c-anca (cytoplasmic anti-neutrophil cytoplasmic antibody), p-anca (perinuclear anti-neutrophil cytoplasmic antibody), a typical-anca로분류할수있으며, 베 게너육아종증 (Wegener granulomatosis), Microscopic polyangitis 및Churg-Strauss syndrome과같은혈관염의감별진단에이용할수있다. 결체조직질환에서 ANCA 양성률은 30%, atypical-anca 양성률은 11-39% 라고보고되어있다 9. 염증성장질환에서 p-anca 의양성률은궤양성대장염에서 66%, 크론씨병에서 15% 로보고되고있으며 10, 이는면역학적질환과관련성은있으나혈관염과는관련성이없는대부분 atypical-anca로알려져있다. 간접형광면역법과효소면역측정을종합하여이용하면결체조직질환환자에서혈관염을진단하는데있어특이도는 99.5% 에이른다 9. 본환자의경우 ANCA의 subtype 까지확인하지못하여이를확인할수는없으나, ANCA 양성이 Goodpasteur 증후군과관련하여나타난혈관염의표시자로서나타난것인지혹은염증성장질환과관련하여나타난 atypical-anca 양성인지를구분하기는어려울것으로생각된다. Goodpasture 증후군의초기치료로는혈장교환술과고용량의스테로이드와면역억제제의혼합치료가추천되며, 치료시점이적절한경우급격하게임상증상의호전을보인다 6,11. 본환자의경우중증의빈혈로인하여 3일동안농축적혈구 7 pint 투여후에발생한호흡곤란및폐부종의소견을보여백혈구항체에의한수혈관련된급성폐손상 (transfusion related acute lung injury) 12 으로생각되어보존적치료를시행하였으나, 반응을보이지않았다. 처음에 methylprednisolone 사용후호전을보였으나감량을진행하는도중수일만에재발이되어다시고용량의 methylprednisolone을투여하였으나결국원내감염에의한폐렴으로사망하였다. 16년전크론씨병으로진단받고전신쇠약감과식욕부진을주소로내원하여시행한검사에서 Goodpasture 증후군으로진단한예를국내에서처음으로문헌고찰과함께보고하는바이다. 요약 Goodpasture 증후군은원인불명의병인을가진드문질환으로질병의경과가급속히진행하므로조기 387

5 SM Park et al: A Case of Goodpsture Syndrome combined with Crohn Disease 에진단을하여조기에치료방법을결정하는것이질병의예후와큰연관성을가진다. 크론씨병에서혈관염에의한폐합병증을보이는경우는드물어국내에는이와관련된보고가없었으며, 17년전항문누공과농양으로크론씨병으로진단받고 10년전전대장절제술을시행한이후추적관찰하는도중발견된 Goodpasture 증후군 1예를경험하였기에문헌고찰과함께보고하는바이다. 참고문헌 1. Brenner BM, Rector FC. The Kidney. 7th ed. Philadelphia: WD Sanuders; Lerner RA, Glassock RJ, Dixon FJ. The role of antiglomerular basement antibody in the pathogenesis of human glomerulonephritis. J Exp Med 1967;126: Levy JB, Tunrer AN, Rees AJ, Pusey CD. Long term outcome of antiglomerular basement menbrane disease treated with plasma exchange and immunosuppression. Ann Intern Med 2001;134: Plaisier E, Borradori L, Hellmark T, Wattiaux MJ, Flageul B, Mougenot B, et al. Anti-glomerular basement membrane nephritis and bullous pemphigoid caused by distinct anti-alpha 3(IV)NC1 and anti-bp180 antibodies in a patient with Crohn disease. Am J Kidney Dis 2002;40: Hibbs AM, Cizman BB, Guttenberg M, Goldberg B, Meyers K. Ulcerative colitis in a renal transplant patient with previous Goodpasture disease. Pediatr Nephrol 2001;16: Sinico RA, Radice A, Corace C, Sabadini E, Bollini B. Anti-glomerular basement membrane antibodies in the diagnosis of Goodpasture syndrome: comparision of different assays. Nephrol Dial Transplasnt 2006; 21: Storch I, Sachar D, Katz S. Pulmonary manifestations of inflammatory bowel disease. Inflamm Bowel Dis 2003;9: Kuzela L, Vavrecka A, Prikazska M, Drugda B, Hronec J, Senkova A, et al. Pulmonary complications in patients with inflammatory bowel disease. Hepatogastroenterology 1999;46: Merkel PA, Polisson RP, Chang Y, Skates SJ, NilesJL. Prevalence of antineutrophil cytoplasmic antibodies in a large inception cohort of patients with connective tissue disease. Ann Intern Med 1997;126: Quinton JF, Sendid B, Reumaux D, Duthilleul D, Cortot A, Grandbastien B, et al. Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut 1998;42: Kelly PT, Edward EF. Goodpasture syndrome: molecular and clinical advances. Medicine 1994;73: Mason. Murray & Nadel s textbook of respiratory medicine. 4th ed. Saunders;

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,