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대한소화기학회지 2010;56:255-259 DOI: 10.4166/kjg.2010.56.4.255 궤양성대장염환자에서발생한하대정맥혈전증과급성췌장염 1 예 성균관대학교의과대학내과학교실 신도현ㆍ이광혁ㆍ김치훈ㆍ김갑현ㆍ박성현ㆍ장동경ㆍ이종균ㆍ이규택 A Case of Inferior Vena Cava Thrombosis and Acute Pancreatitis in a Patient with Ulcerative Colitis Do Hyun Shin, M.D., Kwang Hyuk Lee, M.D., Chi Hoon Kim, M.D., Kap Hyun Kim, M.D., Sung Hyun Park, M.D., Dong Kyung Chang, M.D., Jong Kun Lee, M.D., and Kyu Taek Lee, M.D. Department of Internal Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea A 21-year-old man admitted complaining of sudden severe epigastric pain for 1 day. He had been diagnosed as ulcerative colitis (UC) and taking mesalazine for two months. UC was in nearly complete remission at admission. He never drank an alcohol, and serum amylase was 377 IU/L. CT scan showed inferior vena cava (IVC) thrombosis in addition to mild acute pancreatitis. To evaluate the cause of acute pancreatitis and IVC thrombosis, magnetic resonance cholangiopancreatogram (MRCP), endoscopic ultrasonogram (EUS), lower extremity Doppler ultrasonogram (US) and blood test of hypercoagulability including factor V, cardiolipin Ab, protein C, protein S1, antithrombin III, and anti phospholipids antibody were performed. There was no abnormality except mild acute pancreatitis and IVC thrombosis in all the tests. He was recommended to stop taking mesalazine and start having anticoagulation therapy. After all symptoms disappeared and amylase returned normal, rechallenge test with mesalazine was done. Flare-up of abdominal pain occurred and the elevation of serum amylase was observed. Ulcerative colitis came to complete remission with short-term steroid monotherapy. Acute pancreatitis and IVC thrombosis were completely resolved after 3-month anticoagulation therapy with no more mesalazine. We postulated that IVC thrombosis occurred due to hypercoagulable status of UC and intra-abdominal inflammation caused by mesalazine-induced pancreatitis. (Korean J Gastroenterol 2010;56:255-259) Key Words: Ulcerative colitis; Inferior vena cava thrombosis; Acute necrotizing pancreatitis; Mesalazine 서론궤양성대장염과연관된여러가지전신적합병증중하나인혈전증은약 1.3-6.7% 정도발생하는것으로알려져있다. 궤양성대장염의활동도가증가할수록발생빈도가증가 하고주로폐동맥과심부정맥 (deep vein) 에잘발생한다. 1-3 염증성장질환에서급성췌장염의빈도가높은데, 이는궤양성대장염환자에서특발성췌장염이발생하는경우가많고궤양성대장염치료약제에의한췌장염의발생이흔해서이다. 4-6 특히염증성장질환의치료에쓰이는 5-amino- 접수 : 2010 년 5 월 13 일, 승인 : 2010 년 6 월 11 일연락처 : 이광혁, 135-710, 서울시강남구일원동 50 번지삼성서울병원소화기내과 Tel: (02) 3410-3409, Fax: (02) 3410-3896 E-mail: kwanghyuck.lee@smc.samsung.co.kr Correspondence to: Kwang Hyuk Lee, M.D. Department of Gastroenterology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Irwon-dong, Gangnam-gu, Seoul 135-710, Korea Tel: +82-2-3410-3409, Fax: +82-2-3410-3896 E-mail: kwanghyuck.lee@smc.samsung.co.kr

256 대한소화기학회지 : 제 56 권제 4 호, 2010 Fig. 1. Diffuse hyperemic edema, erythema, superficial ulcers with whitish exudates were observed during an initial colonoscopy (A). After two months, nearly complete remission was observed during admission due to acute pancreatitis (B). salicylic acid (ASA), sulfasalazine, azathioprine에의해서급성췌장염이발생한증례가보고되고있다. 7-9 하지만궤양성대장염환자에서약제에의한췌장염과하대정맥혈전증이동시에발생한증례의보고는없었다. 거의관해가온궤양성대장염환자에서 5-ASA에의한급성췌장염과하대정맥혈전증이동시에발생한증례를최근에경험하였기에보고한다. 증 례 21세남자가내원 1일전부터갑자기발생한심한상복부통증과오심을주소로응급실로내원하였다. 환자는 2년전에대뇌와척수에병발된다발성경화증 (multiple sclerosis) 진단받고현재까지인터페론 (interferon beta 1b) 치료를하면서관해상태에있었으며일상적인활동에전혀지장이없었다. 4개월전부터시작된복통, 설사, 혈변등의증상이있어대장내시경을시행하였다. 검사한대장내시경에서전대장에걸친발적, 미란, 부종및소궤양등의병변이직장부터연속적으로관찰되었으며조직검사결과활동성궤양성대장염으로진단받았다 (Fig. 1A). 2개월간 mesalazine 과 prednisolone을복용하고장증상은거의소실되었다. 내원 1일전부터갑자기지속적인상복부통증을동반한심한오심과구토가발생하였다. 통증으로거의음식을섭취할수없었으며, 허리를펴면악화되는양상을보였다. 개인력과과거력에서흡연과음주는하지않았고가족력에서도특이사항은없었다. 궤양성대장염치료제와인터페론외의다른약물의복용력도없었다. 응급실에서측정한체온은 38.1 o C, 맥 Fig. 2. Abdominal CT showed diffuse pancreatic swelling, peripancreatic infiltration with fluid collection and the fluid was extended to the left anterior pararenal space. However, there was no other remarkable finding on the pancreatobiliary systems. 박수 109회 / 분, 혈압 122/64 mmhg, 호흡수는 19회 / 분이었다. 공막의황달은관찰되지않았으며상복부에압통이있었으나반발통은없었다. 일반혈액검사에서백혈구 19,120/mm 3 ( 호중구 82%, 림프구 8%), 혈색소 11.5 g/dl, 혈소판 456,000/ mm 3 이었으며, 적혈구침강속도 (ESR) 41 mm/hr, CRP 1.3 mm/hr였다. 생화학검사에서 AST 21 IU/L, ALT 16 IU/L, 총빌리루빈 0.7 mg/dl, 혈당 117 mg/dl, 아밀라아제 377 IU/L, 리파아제 816 IU/L, 총콜레스테롤 115 mg/dl, 중성지방 59 mg/dl이었으며면역글로블린 (IgG) 967 mg/dl ( 정상범위 700-1,600 mg/dl) 이었다. 급성췌장염의감별및중증도판정을위하여시행한복

신도현외 7 인. 궤양성대장염환자에서발생한하대정맥혈전증과급성췌장염 1 예 257 Fig. 3. EUS examination and CT scan showed partially occluding thrombus (white arrows) in the IVC. Fig. 4. Severe abdominal pain and marked elevation of pancreatic enzyme was developed 1 day after a mesalazine was readeministered. His abdominal pain subsided and elevated pancreatic enzymes returned to normal after mesalazine was discontinued. 부전산화단층촬영 (CT) 에서췌장은미만적인부종이보이고, 췌장주위지방침윤과액체저류 (fluid collection) 가관찰되었다 (Fig. 2). 담석이나담관확장소견은없었으나하대정맥에혈전이관찰되었다. 췌담관의합류이상등의선천적기형과미세담석등의췌장염원인을찾기위하여실시한자기공명담췌관촬영 (MRCP) 과내시경초음파 (EUS) 검사에서도하대정맥혈전및급성췌장염외에특이소견은없었다 (Fig. 3). 심부정맥의혈전을확인하기위한하지도플러검사 (extremity duplex scan) 에서도하대정맥의혈전이외의하지의심부정맥혈전은관찰되지않았다. 혈액응고와관련된 fibrinogen, antithrombin III, D-dimer, protein C, protein S1, factor V Leiden mutation, lupus anticoagulant, cardiolipin antibodies 등의혈액검사는음성이거나정상범주였다. 추적내시경검사에서궤양성대장염병변은거의관해 상태였고 (Fig. 1B) 치료약물인 mesalazine 에의한췌장염가능성이있어금식등의보존적치료와 mesalazine 치료를중단하고하대정맥혈전증에대해서는헤파린 (heparin) 정주치료후와파린 (warfarin) 으로전환하였다. 금식및약제투여중단후에복통및발열등의증상은호전되고아밀라제와리파아제수치는감소하였다. 내원 9일째, 복통이완전히소실되고아밀라제수치가정상으로돌아온뒤에궤양성대장염의유지요법에서 mesalazine 이중요한치료제이므로약물유발성췌장염확진을위해서유발검사를하였다. Mesalazine을재투여후다음날심한복통재발과함께아밀라제와리파아제수치가다시상승하였고다시투여중지한후복통호전과아밀라제와리파아제수치가다시감소하여 mesalazine 과민반응으로발생한약물유발성급성췌장염으로확진하였다 (Fig. 4). 이후궤양성대장염은경구스테로이드 2개월치료후경과관찰중이며하대정맥혈전은 3개월간의항응고제투여후완전히소실되었고 9개월뒤추적도플러감사에서도혈전은관찰되지않았다. 현재환자는특별한치료없이외래에서추적관찰중에있다. 고찰이번증례는궤양성대장염환자에서 mesalazine 유발성급성췌장염과하대정맥혈전증이동시에발견된매우드문경우로, 혈전증은장외질환으로발생하였을가능성과췌장염과연관된복강내국소염증이혈전증발생에기여하였을가능성을같이고려하여야하겠다. 궤양성대장염환자에서급성췌장염이발생하면췌장염의원인으로일반적으로흔한음주와담석외에도궤양성대장염과같이병발하는특발성췌장염과치료약제인 5-ASA, sulfasalazine, azathioprine, 6-MP 등에의해발생된췌장염도감별해야한다. 4-10 5-ASA가궤양성대장염의유지요

258 The Korean Journal of Gastroenterology: Vol. 56, No. 4, 2010 법에중요한약물이므로이러한췌장염원인중에서이약물에의한췌장염의감별은향후환자치료결정에중요하다. 이번증례에서는췌장염의다른원인을찾기위하여 MRCP와 EUS를포함한다양한검사를시행하였으나특별한원인을발견하지못하였고 mesalazine 에의한췌장염을의심하여재투여검사를시행하여확진하였다. Mesalazine에의해서발생하는급성췌장염은알레르기반응혹은특이체질반응으로발생한다고생각된다. 11 보고된급성췌장염은약물투여후약 2일에서 1개월사이에주로발생하나 1년이후에도발생하는경우도있었다. 12 투여를중단하면호전되나재투여시다시반응이일찍그리고심하게나타나는것을특징으로한다. 약물의용량과투여기간과의뚜렷한상관관계가있다는보고는없다. 대부분의약물유발성췌장염증례는원인약물투여를중지하고보존적치료만으로호전되었으며심각한합병증은발생하지않았다. 6-9,11 따라서약물유발성췌장염으로생각하고약물을중지하고금식등의보존적치료하였으나 3-7일이후에도호전이없을경우에는약물이아닌다른원인에의한췌장염이발생하였거나합병증이병발했는지확인이필요하다. Mesalazine 에의한약물유발성췌장염의확진은향후궤양성췌장염의치료의결정에중요하다. 따라서, 이전췌장염의정도가심하지않았다면확진을위하여약물유발검사를시행할수있다. 약물에의한췌장염이확진된증례대부분에서스테로이드만으로궤양성대장염의관해가유지되었다. 만약스테로이드에불응하는중증궤양성대장염환자의경우라면 cyclosporine A, infliximab, tacrolimus 등의추가적인약물치료나수술을고려할수있다. 13 다발성경화증환자에서뇌정맥내혈전증이요추천자와스테로이드치료와연관되어발생할수있으며, 질환이악화되어휠체어보행 (wheelchair ambulation) 또는침상생활만 (bedridden status) 가능한경우에혈전증이증가되는것으로알려져있으나 14 그외의경우에서는혈전증이명확히증가했다는보고는없고, 오히려하지의경직으로정맥혈전이감소했다는주장도있다. 이번증례의환자는관해상태에있었고정상적인일상활동이가능하여다발성경화증에의한혈전증발생가능성은거의없다. 이번증례에서는궤양성대장염에대한 2개월간의치료로거의관해에도달한상태에서췌장염과더불어다른부위에는혈전증이없이하대정맥에서만혈전증이발생하였다. 궤양성대장염과병발하는혈전증은 30-40% 정도는비활동성시기에발생한다는보고가있지만 2 일반적으로활동기에더발생한다고알려져있다. 혈전은주로하지정맥에서발생하여폐색전증을일으키는경우가많이보고되어있다. 이외에도상하지의동맥, 뇌동맥, 대동맥, 관상동맥등의동맥내혈전증도발생하였다. 15,16 하대정맥과신정맥 (renal vein) 혈전증이동반된경우가있었으나 17 이번증례처럼하대정맥에단독으로발생한경우보고는없었다. 급성췌장염과연관된혈전증은흔하게비장정맥을비롯하여간문맥, 장간막정맥등에발생하며심한췌장염의합병증으로알려져있고하대정맥에발생한경우는매우드물다. 18,19 따라서, 궤양성대장염의관해기에약제에의한경한췌장염에서하대정맥에혈전증이생긴원인은궤양성대장염혹은췌장염중어느하나의원인으로발생하였기보다는두가지요인이복합적으로작용하여발생한것으로여겨진다. 일반적으로궤양성대장염에서혈전증이발생하면항응고치료를권유하나항응고제유지요법이도움이되는가에대해서는명확하지않다. 부적절한치료는혈전의재발과생명을위협할수있는위험성이있으나질병의활성도가높을경우에서항응고제및항혈소판제의치료가장출혈의합병증을조장할수가있기때문이다. 20 혈전용해제투여와하대정맥필터 (IVC filter) 설치또는수술적인제거등의추가적인치료는혈전의크기와신정맥혈전및폐색전동반여부, 항응고제치료의반응여부, 혈전의악화, 신부전및혈역학적불안정등을고려하여시행할수있다. 궤양성대장염이있으면서하대정맥과신정맥혈전증이발생한증례의경우에는 17 항응고제치료를하였으나지속적으로혈전이진행하면서혈역학적불안정이발생하여하대정맥필터설치와혈전용해제치료를하였다. 이번증례에서는하대정맥혈전증에대해서궤양성대장염이거의관해상태이고출혈이없어서항응고치료를시행할수있었고 3개월치료후에완전히소실되었다. Mesalazine을투여하지않으면췌장염이발생하지않으므로혈전증이재발하지않을것으로생각하고항응고치료를중단하였다. 요약하면, 이번증례는 mesalazine 으로관해가유지되던궤양성대장염환자가 mesalazine 에의한급성췌장염과하대정맥혈전증이발생한증례이다. Mesalazine에의한췌장염은유발검사로확인되어투약을중단하였고하대정맥혈전에대해서는궤양성대장염의관해가유지되어항응고요법을실시하였다. 궤양성대장염으로인한과응고상태에서췌장염에의한복강내국소염증이하대정맥혈전발생에기여한것으로여겨졌으며상기치료로궤양성대장염재발없이췌장염은호전되었고하대정맥혈전은소실되었다. 항응고치료중단후 9개월동안경과관찰하였으나더이상의재발은없었다. 궤양성대장염환자에서이렇게췌장염과하대정맥혈전증이동시에발생한보고는아직까지없었다. 이런경우에치료에있어서궤양성대장염의활동도가조절되면항응고요법이가능하고췌장염의원인이되는약제를중단하여췌장염발생을예방하고혈전이항응고요법중에용해된다면항응고요법을중단할수있음을보여주는증례이다.

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