단순피부병변으로간과되어급성호흡곤란증후군으로진행된쯔쯔가무시병 1 예 건양대학교의과대학내과학교실유기현, 김기홍, 김종대, 손지웅, 나문준, 최유진 A case of ARDS Overlooked Tsutstugamushi Disease that Presented as Simple Cutaneous Lesions Ki Hyun Ryu, M.D., Ki Hong Kim, M.D., Hong Dai Kim, M.D., Ji Woong Son, M.D., Moon Jun Na, M.D., Eugene Choi, M.D. Department of Internal Medicine, College of Medicine, Konyang University Daejon Korea Tsutstugamushi disease is a major febrile disease that generally occurs in the fall in Korea with hemorrhagic fever with renal syndrome and leptospirosis. This disease is often accompanied by interstitial pneumonia, acute renal failure and liver failure. The causative agent, namely Orientia tsutsugamushi, is transmitted to humans through the bite of a laval trombiculid mite, which is commonly known as a chigger. A 78 year old man was admitted in October 2004 with intractable fever and a drowsy mentality. Two weeks earlier, he visited a private clinic complaining of a simple skin rash. He was treated with antihistamine and steroid, but his symptoms were aggravated and he was referred to our hospital. His physical examination and laboratory findings showed a septic shock status. The maculopapular rash had spread over his face, chest, abdomen and extremities. Eschar was observed in lower back area but it was too difficult to distinguish it from other skin rashes. His chest X-ray appeared as diffuse nodular patchy consolidations in the bilateral lung parenchyme. He was treated with a mechanical ventilator and doxycycline under th suspicion of Tsutstugamushi disease. However, he suffered multiorgan failure accompanied by acute respiratory distress syndrome, acute renal failure and acute hepatitis. He was treated in the intensive care unit for approximately 12 weeks and his general condition was recovered. (Tuberc Respir Dis 2006; 61: 389-393) Keywords: Scrub typhus, Acute respiratory distress syndrome, Rash 서 쯔쯔가무시병 (Tsutsugamushi Diseade) 은털진드기병 (Scrub Typhus) 으로알려져있으며, 약 2000년전중국인에의해서처음기술되었고 20세기초반일본인에의해서명명되었다 1. 국내에서는 1951년주한 UN군에서처음발병이보고된이후 1980년대중반에이르러서전향적, 후양적연구에의해그동안의발생가능성을확인되었다 2. 이질환은동물원성 ( 原性 ) 감염증으로 Rickettsia 감염증의하나이며, 사람은 Orientia tsutsugamushi 에감염된좀진드기유충 론 Address for correspondence: Eugene Choi, M.D. Dpartment of Internal Medicine, College of Medicine, Konyang University Hospital 685, Gasowon-Dong, Seo-Gu Daejeon, 302-718 Korea TEL: (042) 600-8834 E-mail: eugene@kyuh.co.kr Received: May. 18. 2006 Accepted: Sep. 4. 2006 (Chigger) 에물렸을때감염된다. 환자들이호소하는증상들은발열, 오한, 두통, 쇄약감, 객담, 복통, 근육통, 구역및구토, 호흡곤란, 발진등매우다양하고호소하는양상또한비특이적이어서증상만으로쯔쯔가무시병을추정한다는것은쉽지않다. 임상증후로피부발진과, 가피 (Eschar), 빈맥, 복부압통, 빈호흡, 인후발적, 피부발진, 결막충혈, 수포음, 간비대, 즉골척추간압통, 부종등을볼수있어 1차진료기관에서도어느정도임상적으로진단을내릴수있으나일부환자에서이러한소견들이관찰되지않는경우가있어진단이늦어지는경우도있다 3. 치료시작후임상적경과는간질성폐렴과급성신부전이소수에서관찰되며 4, GOT, GPT 상승이다수에서관찰되나 1~2 주후에대개정상화된다. 또한대부분의환자에서두통, 근육통, 오한등의증세는알맞은항생제의투여후 1~2일이면호전되기시작하고, 2~3주후에는정상적인사회생활에복귀가이루어진다 5,6. 소수에서는급성호흡부전증후군이동반되게되며, 국내에 389
KH Ryu et al: A case of ARDS overlooked tsutstugamushi disease that presented as simple cutaneous lesions 서는현재까지 4예가발표되었다 7-9. 본저자들은단순피부병변으로오인되어 1차의료기관에서치료받던중발생한간질성폐렴과급성호흡곤란증후군, 급성신부전등이동반된쯔쯔가무시병 1예를경험하였기에이를여러문헌고찰과함께보고하는바이다. 증례환자 : 신 O O 남자. 78세주소 : 의식저하현병력 : 내원 2주전부터발생한발열, 오한, 손에서부터시작된피부발진을주소로피부과병원에서항히스타민제와스테로이드로치료중, 얼굴에서시작하여전신으로번지는발진과함께발열, 핍뇨, 의식저하의소견을보여본원으로전원되었다. 과거력 : 특이사항없음. 사회력 : 흡연력은없었고, 40년간매월 20회소주 3~4잔정도의음주력을가지고있었다. 가족력 : 특이사항없음 신체검사소견 : 생체활력징후에서혈압은 80/60 mmhg, 분당맥박수는 122회, 분당호흡수는 20회, 체온은 38.6도씨였다. 의식은기면상태였으나신경학적검사상이상소견은없었으며, 급성병색을띠고있었다. 안면부에는반점, 구진상의발진이다양한크기로관찰되고있었으며 (Figure 1A), 전흉벽, 전복벽및사지에도마찬가지의다양한모양과크기의반점, 구신상의발진이관찰되었고 (Figure 1B,C), 배부의하부중앙부에전형적인가피 (eschar) 가관찰되었다 (Figure 1D). 결막충혈이나경부림프절종대는관찰되지않았다. 양측폐야에서수포음이청진되고있었고특별히호흡음이감소한부위는없었으며, 빠른심박동을나타내고있었으나병적인심잡음은보이지않았다. 복부검사상장음은정상이었고, 간이나비장의종대는없었다. 검사소견 : 내원당시시행한말초혈액검사상 hemoglobin 12.2 g/dl, hematocrit 32.3%, white blood cell 9,450/mm 3 (neutrophil 49.6%, lymphocyte 39.0%, monocyte2.1%, eosinophil 1.4%), platelet 165,000/ Figure 1. Maculopapular rash was spreaded on skin of face(a), chest, abdomen(b) and leg(c). (D) Eschar was seen in lower back area. 390
Tuberculosis and Respiratory Diseases Vol. 61. No.4, Oct. 2006 mm 3 이었다. erythrocyte sedimentation rate는 90 mm/hr, C-reactive protein 은 19 mg/dl 였다. 소변검사상 protein 2+, glucose ±, blood 3+, white blood cell + 이었다. 생화학검사상 blood urea nitrogen 52.0 mg/dl, creatinine 1.71 mg/dl, aspartate aminotransferase 57 IU/L, alanine aminotransferase 43 IU/L, alkaline phosphate 155 IU/L, total bilirubin 0.85 mg/dl, total protein 5.20 g/dl, albumin 1.78 g/dl, total cholesterol 88 mg/dl calcium 7.72 mg/dl, glucose 293 mg/dl 이었다. 혈청전해질은 sodium 151 mmol/l, potassium 3.65 mmol/l, chloride 123.1 mmol/l 이었다. 혈액응고검사상 prothrombin time 18.6 sec(inr 1.57), activated partial thromboplastin time 51.3sec 이었다. Fibrinogen 4.95 g/l, fibrinogen degradation products (+), D-dimer 6.16 ug/ml 였다. venereal disease research laboratory test (-), HBsAg/HBsAb (-/-), hantan virus Ab (-), rickettsial Ab (+), leptospiral Ab (-) 이었고 tsutsugamushi/ox-k에대한면역혈청검사상 1:1280으로양성이었다. 객담의 acid-fast stain에 의한검사와, 객담, 대변, 혈액배양검사에서동정되는균이없었다. 동백혈가스분석결과는 ph 7.333, PCO 2 70.8 mmhg, PO 2 67.8 mmhg, HCO 3 36.5 mmol/l, O 2 saturation 91.5% 이었다. 본원으로전원되어시행한흉부단순촬영상에서양측폐야에서증가된기관지와혈관상의음영과함께경화소견이관찰되었다 (Figure 2). 임상경과 : 환자는중환자실에입원하여기계환기요법및 doxycyclin을포함한항생제치료를시행하였으나급성신부전, 급성간염과함께급성호흡부전증후근이동반된다발성장기부전의소견을보였다. 호흡기능은지속적으로악화되는소견을보여기계환기요법을중단하지못하고, 17병일째기관절개술을시행하였다. 환자는 24병일째부터간기능과신장기능의호전과함께흉부단순촬영상에서폐렴및폐부종이호전되었다. 이후환자는호흡기능의악화와호전을반복하였으며중환자실치료 87일만에회복되어일반병실로전실되었다. 이후약 1개월간병동치료후현재는퇴원하여외래추적관찰중이다. 고찰 Figure 2. Diffuse lung consolidation in both lung field. 한국에서매년유행하고있는급성열성질환의대부분은신증후출혈열, 쯔쯔가무시병및 leptospira병이라할수있다 10. 이질환들은계절적으로비슷한시기에유행하고초기임상증상이서로유사하기때문에임상적으로감별진단이어려우며, 최종진단은혈청진단법으로만가능하다 3. 쯔쯔가무시병의임상경과는불현성감염에서부터사망에이르기까지상당한차이를보이며일반적으로는감염된좀진드기의유충에물린후약 6~20일의잠복기를거쳐갑자기심한두통이생기고수시간내에오한과전율이생기면서 39 정도의고열, 근육통등의증세가나타난다. 임상증후로는피부발진과, 가피 (Eschar), 빈맥, 복부압통, 빈호흡, 인후발적, 피부발진, 결막충혈, 수포음, 간비대, 늑골척추간압통, 부종등을볼수있어 1차진료기관에서도어느정도임상적으로진단을내릴수있으나일부환자에서는이러한소견들이관찰되지않는경우도있어진단이늦어 391
KH Ryu et al: A case of ARDS overlooked tsutstugamushi disease that presented as simple cutaneous lesions 지는경우가있다. 좀진드기에의해물리는것은통증이없을뿐아니라신체검사하기가어려운액와부나외음부를포함신체어디나가능하다. 이로인해생기는특징적인가피는초감염부위에주로생성되며, 2차감염부위에서는드물고, 작은구진에서시작하여크기가커지면서중앙에괴사를일으켜딱지를형성하게된다. 이는상피와진피가괴사되어발생하는것으로서표피는관찰되지않고, 가피의주위에는발진띠가나타난다. 괴사주위를둘러싸는진피내혈관은대부분혈관염에의하여파괴되거나혈관내혈전이형성되어있고, 혈관주위에단핵구로구성된염증세표의침윤도관찰되나주위의부종은동반하지않는다. 전신적으로는림프절종대와함께발병 1주내반점, 구진상의발진이나타나 2~10일간지속되는데흉복부와안면에흔하고사지에도나타날수있으며, 가렵지않고출혈성이아닌점이특징이다. 이러한발진에서는진피상층부에혈관확장과혈관주위에단핵구로구성된염증세표의침윤을보이며, 대부분의경우발진부위에서 Giemsa 염색과전자현미경상으로도원인균인 R. tsutsugamushi 를증명할수없다. 쯔쯔가무시병의폐합병증은경한폐실질염에서부터급성호흡곤란증후군까지다양한임상양상을보인다. 이 4등의연구에서는흉부단순촬영상음영증가를보인경우가 36% 이었고, 폐간질부의음영증가를보인예가 23% 로폐포내음영증가 (4%) 보다많았으며, 병변은대부분양측성이었다. 그이외에흉부단순촬영상이상소견은심비대 8%, 흉막삼출 8%, 폐문부흉막삼출이 4% 에서관찰되었다. 본증례와같이특징적인가피를간과하고나타난피부의홍반성구진양발진소견만으로약진이나다른단순피부염등으로오인될경우치료시기가늦춰지고오히려스테로이드등의면역억제제사용으로인해병의경과의진행, 악화를초래할가능성이있다. 진단에있어서임상적특징이나단순검사실수치는특이도가떨어지고, 가피가가장유일하고특징적인진단적실마리를제공한다. 최근에는가피조직으로시행한중합효소연쇄반응 (PCR; Polymerase Chain Reaction) 에의해진단된경우가보고되었으며, 순환 하는병원균에대한중합효소연쇄반응역시믿을만한진단적도구가되지만특이항제가있어야만가능하다. 일반적으로쓰이는 Weil-Felix 검사법은민감도와특이도의측면에서효용성이낮고, 확진을위한검사법은간접면역과산효소검사법 (indirect immunoperoxidase test) 과면역현광분석법 (immunofluorescent assay) 이다. 그러나이러한검사의복잡성때문에좀더빠르고, 정확한점적면역분석법 (dot blot immunoassay) 11 이개발되었으나비용면에서효율성이떨어진다. 치료는다른감염증과같이대증치료와함께중증인경우각장기부전에따라인공호흡기나혈액투석기등을사용한다. 항생제의즉각적인치료는질병의경과를단축시키고, 사망률을감소시킬수있기때문에, 경험적항생제를조기에사용하여야한다. 1주간의 doxycycline 경구요법은합병증을동반하지않은경우에주된치료의방법이된다. Doxycyline 의정주요법은경구요법이불가한경우나질병의정도가중증일경우에사용된다. Chloramphenicol 은값이싸기때문에 tetracycline의대용으로사용되었었으나골수독성등의부작용으로인하여현재는거의사용되지않는다. 이외에임산부에게는 erythromycin이나 azithromycin, 8세이하의어린이에게는여기에 rifampin 이나 clarithromycin 등을사용할수있다. 병의경과및예후는대부분의환자에서두통, 근육통, 오한등의증세가알맞은항생제의투여후 1~2일이면호전되기시작하며, 2~3주후에는정상적인사회생활의복귀가가능하다. 그러나고령이거나만성질환자, 병의경과중증증폐렴, 쇽, 뇌염등이합병된경련, 급성호흡부전등이합병할경우에는사망에이를수도있다 12. 본증례와같이병의경과상비특이적소견으로간과되어진행을악화시키고치료가지연되는경우도이에해당할것으로생각된다. 요약저자들은홍반성구진양발진으로발현된쯔쯔가무시병환자에서단순피부질환으로간과하여치료의시기가지연되고스테로이드등의약물사용으로급성 392
Tuberculosis and Respiratory Diseases Vol. 61. No.4, Oct. 2006 신부전및급성호흡부전으로진행된 1례를경험하였기에문헌고찰과함께보고하는바이다. 참고문헌 1. Watt G, Parola P. Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis 2003;16:429-36. 2. Lee JS, An YL, Kim YK, Lee MH. Thirteen cases of rickettsial infection inclnding nine cases of Tsutsugamushi disease first confirmed in Korea. J Korean Med Assoc 1986;29:430-8. 3. Yi KS, Chong YS, Yoo SK, Chun KW, Pae CK, Hong KS, et al. Accuracy of clinical diagnosis of scrub typhus at primary-care clinics in an endemic area. Korean Soc Infect Dis 1996;28:179-84. 4. Lee HS, Kim DS, Chin YJ, Kim SJ, Song HK, Sung NH, et al. A study of interstitial pneumonia in scrub typhus. Korean J Med 1996;50:77-87. 5. Jeon KY, Chang WH. Twenty-four cases of Tsutsugamushi disease which occurred in the Chonbuk area in the fall of 1986 and 1988. Korean J Med 1989;36: 395-403. 6. Lee JK, Lee BS, Shin OS, Shin KC, Oh YK, Ki SG. A clinical study of Tsutsugamushi disease that occurred in the autumns of 1989, and 1990. Korean J Med 1991;41:558-564. 7. Lee CS, Choi SM, Lee HB, Lee YC, Rhee YK. A case of scrub typhus manifested with acute respiratory distress syndrome. Korean J Med 1999;57:216-9. 8. Bae WH, Song SH, Kim TO, An JH, Jung HC, Shin HJ, et al. Two cases of scrub typhus complicating acute respiratory distress syndrome. Korean J Med 2000;59:544-9. 9. Park JS, Jee YK, Lee KY, Kim KY, Myong NH, Seo PW. Acute respiratory distress syndrome associated with scrub typhus: diffuse alveolar damage without pulmonary vasculitis. J Korean Med Sci 2000;15: 343-5. 10. Lee HW. Seroepidemiologic studies of acute hemorrhagic diseases in Korea from 1985 to 1987 (Hemorrhagic fever with renal syndrome, leptospirosis and scrub typhus). J Korean Med Assoc 1988;31:581-93. 11. Coleman RE, Sankasuwan V, Suwanabun N, Eamsila C, Mungviriya S, Devine P, et al. Comparative evaluation of selected diagnostic assays for the detection of IgG and IgM antibody to Orientia tsutsugamushi in Thailand. Am J Trop Med Hyg 2002;67:497 503. 12. Bae WH, Song HS, Kim TO, An JH, Jung HC, Shin HJ, et al. Two cases of scrub typhus complicating acute respiratory distress syndrome. Korean J Med 2000;59:544-9. 393