대한내과학회지 : 제 82 권제 5 호 2012 http://dx.doi.org/10.3904/kjm.2012.82.5.594 Isoniazid 에의한가성용종을동반한급성췌장염 1 예 1 제주한라병원내과, 2 서울대학교의과대학분당서울대학교병원내과, 3 서울시립의료원내과, 4 제주한라병원영상의학과 차병효 1 이상협 2 황진혁 2 김장언 3 이상진 1 이충식 1 김현 4 Isoniazid-Induced Acute Pancreatitis with Pseudocyst Byung Hyo Cha 1, Sang Hyub Lee 2, Jin-Hyeok Hwang 2, Jang Eon Kim 3, Sang Jin Lee 1, Chungsik Lee 1, and Hyun Kim 4 Department of Internal Medicine, 1 Cheju Halla Hospital, Jeju; 2 Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam; 3 Seoul Citizen Hospital, Seoul; 4 Cheju Halla Hospital, Jeju, Korea Numerous medications have the potential to induce acute pancreatitis. However, isoniazid-induced acute pancreatitis is extremely rare. Drug-induced acute pancreatitis can be diagnosed by improvement after stopping the drug and recurrence of pancreatitis when rechallenged. We present a case of severe acute pancreatitis accompanied by multiple large pseudocysts after isoniazid treatment for pulmonary tuberculosis. We confirmed that isoniazid induced pancreatitis by rechallenging after treatment cessation. Most previous reports of isoniazid-induced pancreatitis have been clinically mild forms, and the patient fully recovered with supportive management. However, this case presents severe and permanent pancreatic damage that developed with 5 weeks of isoniazid treatment. When a patient presents with manifestations of pancreatitis during treatment of tuberculosis that includes isoniazid, the physician should consider isoniazid-induced pancreatitis. (Korean J Med 2012;82:594-598) Keywords: Pancreatitis; Isoniazid; Pancreatitic pseudocyst; Tuberculosis 서론약제에의해유발되는췌장염은전체급성췌장염환자중에서 0.1-2% 로보고될정도로매우드물다 [1]. 췌장염을유발할수있는약제로는 100여가지가넘는것으로보고되고있으나 [2] isoniazid 에의한췌장염의경우는극히드문경우 로국외에서는 9예 [3-10], 국내에서는 1예 [11] 가보고된적이있다. 저자들은폐결핵치료도중 isoniazid 에의해발생한가성낭종을동반한중증의급성췌장염증례를경험하였기에보고한다. Received: 2010. 6. 29 Revised: 2011. 1. 3 Accepted: 2011. 2. 11 Correspondence to Sang Hyub Lee, M.D. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 463-707, Korea Tel: +82-31-787-7042, Fax: +82-31-787-7051, E-mail: gidoctor@snubh.org - 594 -
- Byung Hyo Cha, et al. A case of acute pancreatitis with pseudocyst induced by isoniazid - 증 례 환자 : 남자, 40세주소 : 혈청아밀라아제, 리파아제상승현병력 : 환자는내원 3개월전고열로인하여본원호흡기내과에내원하여흉부 X-선검사에서흉수소견이보여흉수천자, 객담도말, 배양검사후결핵으로진단받고항결핵제투여결정하려던중환자와보호자가타병원을원하여전원조치되었다. 전원하여항결핵제투여후 5주경과뒤극심한복통과함께혈청아밀라아제, 리파아제상승, 복부컴퓨터단층촬영상췌장종대, 가성낭종등의소견을보여항결핵제투여를중단하게되었다. 이후경과관찰중연고지관계로다시본원으로전원되어응급실을통해본원신장내과에입원하게되었으며동시에췌장염의적절한치료와원인감별을위하여소화기내과에협진이의뢰되었다. 과거력 : 환자는 20여년전고혈압진단후항고혈압제를복용중이었으며 9년전말기신부전증으로진단후정기적인혈액투석을받고있었던중, 내원 5개월전사체기증신장이식술을받았으나 7일뒤급성거부반응으로다시주 3회혈액투석을시작해현재까지지속하고있다. 객담배양검사에서폐결핵으로진단된후 5주간항결핵제를복용하였으며췌장염발생이후내원당시까지 2주동안중단한상태였다. 췌장염발생당시환자가복용한약물은 amlodipine 10 mg, carvedilol 50 mg, valsartan 80 mg, pantoprazol 20 mg qd, sucralfate 1,000 mg tid, prednisolon 15 mg, tacrolimus 4 mg, ferrous sulfate 256 mg을복용하고있었으며 Darbepoietin alfa 40 mcg 주 1회피하주사중이었다. 5주간복용했던항결핵제는 isoniazid 300 mg, rifampicin 600 mg, pyridoxine 50 mg을매일투여하였고 ethambutol 1,200 mg, pyrazinamide 1,500 mg은주 3회격일로투여하였으며내원 2주전중단한상태였다. 이학적소견 : 내원당시환자는활력징후는혈압 150/100 mmhg, 맥박 95회 / 분, 호흡수 16회 / 분, 체온 36.6 로안정적이었다. 흉부청진상우폐야에호흡음이감소되어들렸고복부검진상복부가약간팽창된느낌이었으나압통이나반발통은없었다. 검사실소견 : 백혈구 4,630/uL, 혈색소 9.9 g/dl, 혈소판 97,000/uL, 총빌리루빈 2.57 mg/dl, 알칼리포스파타제 181 IU/L, AST/ALT 41/14 IU/L, 아밀라제 132 IU/L, 리파아제 196 IU/L Figure 1. Amylase and lipase profile of the patient. (Fig. 1), 중성지방 367 mg/dl, 이온화칼슘 1.45 mmol/l, IgG4 0.1 g/l로보고되었다. 내원시 APACHE II score [12,13] 는 13 점이었다. 영상의학적소견 : 타병원에서췌장염진단시촬영한복부컴퓨터단층촬영상췌장의비균질한음영과부종이보였으며췌장주위두군데이상에서복강내체액저류소견을확인할수있어 CT severity score [14] 3점인중증의췌장염으로진단할수있었다 (Fig. 2A and 2B). 경과및치료 : 입원후 3일뒤혈청아밀라제, 리파아제가정상화된후반복적으로혈액검사를시행하면서 isoniazid 를제외한 rifampicin, ethambutol, pyrazinamide를투여하였고, 1 주일뒤 isoniazid 300 mg을재투여하였다. Isoniazid 를다시투여한지 10일째, 환자는열과함께복통을호소하여췌장염의재발을의심하여혈액검사와복부컴퓨터촬영을다시시행하였다. 검사실소견에 isoniazid 재투여당시 97 IU/L, 146 IU/L 이었던아밀라제, 리파아제수치가 206 IU/L, 366 IU/L로상승하였음을확인하였다 (Fig. 1). 복부컴퓨터단층촬영결과에서는크기가증가된가성낭종내부에동맥류가발견되었으며낭종내출혈을의심할수있는조영증강부위가확인되었다 (Fig. 2C and 2D). 환자는 isoniazid 중단, 금식과수액치료, 통증에대한대증치료후혈청아밀라제, 리파아제는정상화되었으나약물투여에도호전되지않는지속적인복부팽만감과복통을호소하여경피적가성낭종배액술을시행하였고, 검붉은색의액체와응고된혈액덩어리들이배액되었다. 시술후통증이경감되었으며우려했던급성출혈은일어나지않았다. 1주간배액관유지후경과관찰을위해시행한복부컴퓨터단층촬영에서가성낭종크기는감소되었다. 이후추가배액을위해 - 595 -
- 대한내과학회지 : 제 82 권제 5 호통권제 621 호 2012 - A B C D Figure 2. CT findings during the initial pancreatitis episode (A, B) and second episode after rechallenge. (C, D) Enlarged pseudocyst and several intracystic enhanced materials suggests a newly developed intracystic hemorrhagy. 배액관을 1-2주더유지하려했으나배액후일시적으로호전되었던발열이다시발생하고항생제변경투여에도호전이없어배액관을통한감염때문인것으로생각하여배액관을제거하였다. 환자는 isoniazid 를제외한항결핵제 3제 (rifampicin, ethambutol, pyrazinamide) 로결핵치료를유지하였고이후더이상의복통과췌장아밀라제, 리파아제의상승은없었다. 이후 1개월뒤시행한복부컴퓨터단층촬영에서도췌장과가성낭종에큰변화가없었다. 고찰약제에의한급성췌장염은전체급성췌장염의 0.1-2% [1] 로드물게보고되고있으나급성췌장염으로진단된환자중에서알콜이나담석증, 자가면역성췌장염혹은외상, 고칼슘혈증이나고중성지방혈증등다른원인들이모두배제된후에도그원인을알수없는경우반드시고려해보아야한다 [1,2,15]. 췌장염을일으킬수있는것으로보고된약제들은매우다양하며 Trivedi 등은보고된증례의빈도에따라서세가지군으로나누어보고한적이있다 [2]. 약제유발성췌장염을진단하기위해서는일단앞에서언급한주요원인들이배제된이후의심되는약제의중단에따른증상과검사실소견의호전을확인한후동일한약제의재투여시다시췌장염이유발되는임상적경과를확인하여진단할수있다 [2]. - 596 -
- 차병효외 6 인. Isoniazid 에의한가성용종을동반한급성췌장염 1 예 - Isoniazid 는 50여년전부터최근까지널리사용되는 1차항결핵약제로그부작용으로는위장관계부작용과간독성, 신경계부작용, 피부과적이상, 혈액학적이상등에대해서는잘알려져있으며드물게루푸스양반응, 임파선종대, 시신경염등이보고된다 [16]. 하지만약제유발성췌장염에대해서는국내에서 1예, 국외에서 9예가보고될정도로극히드물다. Isoniazid 혹은다른약제들이췌장염을일으키는병리기전에대해서는이전의몇몇연구에서 rifampicin과 isoniazid 를포함한약제들의과민성반응을기전으로제시한바가있으나아직명확히밝혀지지않았다 [5]. 국외에서보고된증례를보면 isoniazid 에의해유발되는췌장염에서연령대는 25세에서 80세까지였으며대체로 isoniazid 초기투여후유발되는기간은 0.5일에서 21일까지, 중단한뒤재투여후재발되는기간은 2시간부터 21일까지로다양하게나타났다. 항결핵치료다재요법으로투여한경우외에 isoniazid 단독으로치료한경우도보고되어있다 [3]. 이들대부분의증례에서는주로췌장아밀라제와리파아제의상승으로진단되었으며대체로경증의췌장염으로그경과도큰합병증소견이없이호전되는경우가많았다. 국내에서도폐결핵으로진단후항결핵제투여 18일째혈청아밀라제, 리파아제의상승으로췌장염을확인하고재투여 13일뒤다시검사실소견의상승으로 isoniazid 에의한췌장염을진단하였으며 isoniazid 의중단이후더이상의합병증이나췌장염의재발없이보존적요법만으로치료가된경증의췌장염 1예를 Chung 등 [11] 이보고한바가있다. 그러나국외와국내의증례들이경증의췌장염으로 isoniazid 의중단과보존적요법만으로정상에가깝게호전이된경우들이대부분이었으나이번증례처럼중증의췌장염이유발되어췌장가성낭종이나낭종내동맥류를형성할정도로중증도가심한경우는없었다. 이번증례의경우췌장염진단당시에 Atlanta 분류 [17] 에의한중증도분류에서중증으로분류되었으며 APACHE score, CT severity score 등을기준으로했을때에도중증으로판정되었다. 또한임상경과도영구적인췌장의손상을초래하여보존적치료에호전되지않았던경우로현재까지보고된국내, 국외의증례들에비해훨씬중증의췌장염이 isoniazid 투여 5주만에발생되었다는점에서또다른의의가있다고할수있다. 이번증례에서는폐결핵으로항결핵치료도중 isoniazid 에의한가성낭종을동반한중증의급성췌장염이유발되었으며 약제중단에의해호전되었다가 isoniazid 재투여 10일후다시악화된경우로다른췌장염을유발할수있는감별진단을배제한뒤 isoniazid 에유발된급성췌장염으로진단되었기에문헌고찰과함께보고한다. 중심단어 : 췌장염 ; 췌장가성낭종 ; 결핵 REFERENCES 1. Balani AR, Grendell JH. Drug-induced pancreatitis: incidence, management and prevention. Drug Saf 2008;31:823-837. 2. Trivedi CD, Pitchumoni CS. Drug-induced pancreatitis: an update. J Clin Gastroenterol 2005;39:709-716. 3. Chow KM, Szeto CC, Leung CB, Li PK. Recurrent acute pancreatitis after isoniazid. Neth J Med 2004;62:172-174. 4. Briongos-Figuero LS, Bachiller-Luque P, Pons-Renedo F, Eiros-Bouza JM. Isoniazid-induced acute pancreatitis. Enferm Infecc Microbiol Clin 2007;25:217-218. 5. Izzedine H, Launay-Vacher V, Storme T, Deray G. Acute pancreatitis induced by isoniazid. Am J Gastroenterol 2001; 96:3208-3209. 6. Jin CF, Sable R. Isoniazid-induced acute hepatitis and acute pancreatitis in a patient during chemoprophylaxis. J Clin Gastroenterol 2002;35:100-101. 7. Kvale PA, Parks RD. Letter: acute abdomen: an unusual reaction to isoniazid. Chest 1975;68:271-272. 8. Mendoza JL, Larrubia JR, Lana R, Espinós D, Díaz-Rubio M. Acute pancreatitis induced by isoniazid, a casual association. An Med Interna 1998;15:588-590. 9. Rabassa AA, Trey G, Shukla U, Samo T, Anand BS. Isoniazid-induced acute pancreatitis. Ann Intern Med 1994;121:433-434. 10. Stephenson I, Wiselka MJ, Qualie MJ. Acute pancreatitis induced by isoniazid in the treatment of tuberculosis. Am J Gastroenterol 2001;96:2271-2272. 11. Chung BH, Nam HS, Kwon JH, et al. A case of isoniazid induced acute pancreatitis. Tuberc Respir Dis 2004;56: 411-414. 12. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818-829. 13. Ho KM, Dobb GJ, Knuiman M, Finn J, Lee KY, Webb SA. A comparison of admission and worst 24-hour acute physiology and chronic health evaluation II scores in predicting hospital mortality: a retrospective cohort study. Crit Care 2006;10:R4. 14. Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acute pancreatitis: value of CT in establishing prognosis. Radiology 1990;174:331-336. - 597 -
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