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1 대한내과학회지 : 제 82 권제 4 호 간농양으로발현된톡소카라증의임상적고찰 대구가톨릭대학교의과대학내과학교실 주동욱 김병석 하경호 박경찬 류정일 이창형 Clinical Evaluation of Toxocariasis Presenting as a Liver Abscess Dong Wook Joo, Byung Seok Kim, Kyung Ho Ha, Kyoung Chan Park, Jung Il Ryu, and Chang Hyeong Lee Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea Background/Aims: Toxocariasis rarely causes a liver abscess. We assessed clinical and laboratory manifestations as well as therapeutic responses in patients with toxocariasis presenting as a liver abscess. Methods: Fourteen patients with toxocariasis presenting as a liver abscess were analyzed retrospectively. Symptoms, occupational history, dietary habits, contact with pets, allergic disease, peripheral eosinophil count, serum immunoglobulin E (IgE) level, and invasion to other organs were evaluated. After treatment with albendazole, follow-up was conducted with abdominal computed tomography (CT) and the measurement of serum eosinophil and IgE levels. Results: Among 568 patients with a liver abscess, 14 were diagnosed with active toxocariasis. The mean age of the patients was 48 years, and nine (64%) were men. Four (28.6%) patients had pain in the right upper quadrant of the abdomen or epigastric area, one had cough, and the others (64.3%) had no symptom. Pulmonary involvement was noted in five patients and colon involvement in one. Six (42.9%) patients had a recent history of eating raw meat. Initial laboratory findings showed increased eosinophil and IgE levels in all patients. The initial CT showed one or multiple ill-defined, hypodense lesions in the liver. After 1 month of albendazole treatment, eosinophil counts were normalized or had decreased in 13 (93%) patients. On follow-up CT, liver abscesses disappeared within 6 months after therapy in 92% of patients. Conclusions: Symptoms, laboratory findings, and treatment of a liver abscess caused by toxocariasis differ from those of a pyogenic liver abscess. Early serologic testing may increase diagnostic yield and efficacy of treatment in patients with a liver abscess and peripheral eosinophilia. (Korean J Med 2012;82: ) Keywords: Toxocariasis; Liver Abscess Received: Revised: Accepted: Correspondence to Byung Seok Kim, M.D., Ph.D. Department of Internal Medicine, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu , Korea Tel: , Fax: , kbs9225@cu.ac.kr
2 - The Korean Journal of Medicine: Vol. 82, No. 4, 서론톡소카라증 (Toxocariasis) 은개회충이나고양이회충에의한동물원성감염증이다. 감염은동물과가까운접촉또는동물의배설물에오염된흙이나채소를통해충란을섭취하거나연장숙주 (paratenic host) 생식을통해유충을섭취함으로써일어난다 [1]. 성인보다는유아나학령기아동에서주로감염되며검사소견으로대개말초혈액호산구와혈청 IgE 가증가한다. 대부분무증상이나간, 폐, 안구, 뇌등다양한장기에유충이침범하여염증이나괴사반응을일으킬수있다 [2]. 성인에서간농양으로발현된톡소카라증은매우드문경우로서저자들은이러한환자들을분석하여임상양상, 검사소견, 치료및경과를알아보고자하였다. 간농양의진단은복부 CT를이용한영상소견을기준으로하였다. CT에서호산구성농양이의심되거나간농양소견과함께혈청호산구수가증가한경우에는간조직검사와혈청효소면역측정법 (enzyme-linked immunosorbent assay, ELISA) 을통한기생충항체검사를시행하였으며톡소카라에대한특이항체가양성인경우에톡소카라증으로진단하였다. 하지만현성감염을시사하는호산구증가증이나혈청 IgE 증가가없는경우, 간농양치료를위해기생충치료외에항생제치료를병행한경우, 기생충치료를하였어도이후추적검사를하지않은경우는제외하였다. 톡소카라증의치료로 albendazole 10 mg/kg/day을 5일동안경구투여하였으며 [2] 치료후에 CT, 말초혈액호산구수, 혈청 IgE를추적검사하여치료반응을평가하였다. 대상및방법 결 과 2008년 1월부터 2011년 7월까지대구가톨릭대학교병원에서간농양으로진단된환자들중에서그원인이톡소카라증인환자를대상으로하였다. 의무기록을통하여환자들의증상, 직업력, 식습관, 애완동물접촉여부, 알레르기질환유무, 말초혈액호산구수, 혈청 IgE, 다른장기의침범유무등을조사하였다. 다른장기의침범은호산구침윤을기준으로하였는데폐침범은호산구성폐렴의특징적인 CT 소견으로정하였고장침범은조직검사에서호산구침윤이관찰되는것으로정하였다. 총 568명의간농양환자중 14명 (2.5%) 에서톡소카라증이진단되었으며이들의평균연령은 48세 (34-74세) 로남자가 9 명, 여자가 5명이었다. 4명은입원치료를하였고나머지 10 명은외래에서치료를하였다. 평균추적관찰기간은 7개월 (1-17개월) 이었다. 증상으로는우상복부또는심와부통증이 4예 (28.6%), 기침 1예가있었고나머지 9예 (64.3%) 에서는특이증상이없었다. 간외의장기침범으로는폐침범이 5예 (35.7%), 대장침범이 1예 (7.1%) 있었다. 직업력, 알레르기병력에서특이사항이없었고애완동물과접촉한경우도 A B Figure 1. Microscopic findings (hematoxylin and eosin, 400). (A) Hepatocytes are atrophic due to infiltration by inflammatory cells, most of which are eosinophils. (B) Eosinophilic infiltration is noted within necrotic debris
3 - Dong Wook Joo, et al. Toxocariasis presenting as liver abscess - A B Figure 2. Abdominal computed tomography (CT) findings. (A) CT scan shows a 6.1 cm hypodense lesion with amorphous configuration in segment 7. (B) CT scan shows complete improvement of the lesion 3 months after albendazole treatment. 없었으나 6예 (42.9%) 에서소의육회나간을생식했던과거력이있었다. 대상환자들의초기혈액검사에서호산구수는 ,500/mm 3 ( 정상치 < 500/mm 3 ) [3] 으로상승된소견을보였으며혈청 IgE는 108- > 2,000 IU/mL ( 정상치 < 100 IU/mL) 로다양하게증가된소견을보였는데, 초기혈청 IgE를검사했던 13예중 69% 에서 1,000 IU/mL 이상을나타내었다. 초기복부 CT에서는단일또는다발성의저음영병변을보였다. 7예 (50%) 에서초음파유도하간조직검사가시행되었는데, 모두호산구침윤이동반된간실질괴사소견이관찰되었으며 (Fig. 1) 유충이동정된예는없었다. Albendazole 치료 1개월후호산구수는 6예 (42.9%) 에서정상화되었고, 7예 (50%) 에서정상화되지는않았지만감소소견을보였으며, 1예 (7%) 에서는증가하였으나 3개월후정상화되었다. 치료 1개월후 10예에서혈청 IgE 추적검사가시행되었는데, 2예 (20%) 에서감소, 3예 (30%) 에서증가, 5예 (50%) 에서는변화가없었다. 치료 1-6개월후에복부 CT 추적검사가 12예에서시행되었는데, 11예 (92%) 에서농양이완전히소실되었고 (Fig. 2) 1예에서는농양크기의감소를보였다. 고찰톡소카라에의한인체감염은 1952년에최초로보고된이래 [4], 세계적으로유병률이다양하게보고되고있다 년우리나라시골지역에서정상성인을대상으로한혈청 톡소카라검사에서양성률이약 5% 였다 [5]. 충분히요리되지않은고기, 동물의내장, 오염된토양에서얻어진생야채등을통하여개나고양이에서배출된충란을사람이섭취한후소장에서부화된유충이간을비롯한폐, 안구, 뇌, 심장등다양한장기로이동하면서출혈, 괴사와같은직접적인손상과호산구침윤과같은면역반응을유발할수있다 [2,6,7]. 본연구에서조사한생식과애완동물접촉기왕력으로는감염경로를설명하기에부족하다. 야채를많이먹는국내의식생활양상을고려하여오염된토양을통한감염가능성을고려해야하나, 아직국내토양오염의정도에대해서는알려진바가없다 [7]. 따라서톡소카라증의감염경로가뚜렷하지않아도 CT에서호산구성간농양이의심되거나간농양소견과함께혈액검사에서호산구증가증을보이는경우에는톡소카라증에대한감별이필요할것이다. 일반적인화농성간농양의증상은약 90% 에서고열이있고, 50-75% 에서복부통증이있으며, 그외오심, 구토, 체중감소, 황달등이있을수있는반면 [8,9], 톡소카라증은무증상감염에서부터심한장기손상까지다양하게나타날수있는데이것은충체수, 유충의침범장기, 환자의면역반응에의해결정된다 [10]. 본연구에서는대상환자수가적긴하였으나 64% 에서무증상이었고고열이나오한은없었으며가장흔한증상으로우상복부또는심와부통증이 28.6% 에서있었다. 톡소카라증에의한간침범양상은간비대또는결절로나타나며 [11], 병리학적으로는국소성호산구침윤,
4 - 대한내과학회지 : 제 82 권제 4 호통권제 620 호 호산구성농양, 호산구성육아종등의소견을보인다 [12]. 호산구성간농양의특징적인 CT 소견은다발성병변으로대부분 2 cm 이하이며, 원형또는난원형의형태를띠며, 경계는불분명하고테두리조영증강이적다. 그내부음영은주변간조직에비하여약간낮은음영을보이고간의다중시기 (multiphasic) CT에서는동맥기나지연기에서보다정맥기에서가장뚜렷하다. 지연기에는주변조직과비슷한음영을보이는경향이있기때문에다중시기 CT가아닌 CT에서는병변을찾지못할수도있다 [13]. 본연구에서는다발성병변이 8명 (57%) 에서관찰되었고, 2 cm 이하의병변은 10명 (71%) 에서관찰되었으며, 모양은모두경계가불분명한난원형또는원형이었다. 병변의조영양상은모두주변간조직보다낮은저음영을보였으며위치는우엽 (57%), 양엽 (29%), 좌엽 (14%) 순으로분포하였다. 톡소카라증에의한폐침범의특징적인 CT 소견은다발성으로폐변연부에서젖빛유리 (ground glass opacity) 양상이나폐경결을보이며다른호산구성폐질환과큰차이는없다 [7,14,15]. 검사실소견으로화농성간농양환자에서는일반적으로호산구나 IgE 상승은없으며호중구성백혈구증가를보이는반면, 톡소카라증에의한간농양환자에서는백혈구증가증, 호산구증가증, 고감마글로불린혈증, 빈혈이관찰될수있고 [16], 대변검사로는기생충을진단하기어렵다. 이는인체내에서유충이성충으로성장하지못하고, 대변으로충란이나올수없기때문이다 [12]. 본연구에서는조직검사를통해호산구성농양은확인되었지만톡소카라유충이발견된경우는없어서, 이전문헌보고와마찬가지로조직검사를통해톡소카라증을진단하기는어려울것으로생각된다 [12]. 따라서 ELISA를통해톡소카라증을대부분진단하게되는데민감도는 91%, 특이도는 86% 로알려져있으며 [17] ELISA 양성반응은 western blot 으로확진될수있다 [18]. ELISA 는유충의상표피 (epicuticle) 에서분비되는항원 (Toxocara excretory secretory antigen, TES-Ag) 에대한 IgG 항체를측정하는것으로 TES-Ag은 T-helper type 2 (Th2) 면역반응과함께 interleukin-4 (IL-4) 및 IL-5를증가시키는당단백혼합물이다 [19,20]. 유충에대한 IgG 항체의지속기간이아직까지잘알려져있지않은데, 유충은육아종내에서죽거나살아있는상태로수년간지속되기도하며치료받은후에재감염의가능성도있어 ELISA 를한번검사하는것으로는과거감염과현성감염을구분할수없다 [21]. 따라서호산구증가증과함께혈청 ELISA 에서양성반응을보인 다면현성감염을시사하지만호산구증가증이없다면 500 IU/mL 이상증가된혈청 IgE 농도가현성감염의진단에도움이될수있다 [21]. 그외에도활성화된호산구에서분비되는 eosinophil cationic-protein (ECP) 의측정도도움이될수있다 [21,22]. 톡소카라증은천천히자가호전되는질환으로지속적인감염이없고무증상이라면치료를요하지않는다 [10]. 하지만간농양으로발현되는임상적으로중요한톡소카라증은 thiabendazole, albendazole, mebendazole, diethylcarbamazine 등으로치료해야한다. Thiabendazole은 albendazole에비해효과가낮고 [23], mebendazole은장관외에서흡수율이낮아 2 차약제로사용해볼수있으며 [2], diethylcarbamazine은부작용이많다 [24]. 본연구에서는모두 albendazole로치료하였는데, 치료전증가되었던말초혈액호산구수는치료 1개월후대부분 (93%) 정상화또는감소되었으며치료전 CT에서관찰되었던간농양은치료 6개월내에대부분 (92%) 소실되었다. 하지만혈청 IgE는치료후다양한반응을보여치료반응을평가하기엔부적절하였다. 다른문헌보고에서도 [24] 치료후평균호산구수가 1개월내에의미있게감소하였지만혈청 IgE는큰변화가없었다고하여, 치료후추적검사의지표로서말초혈액호산구수가유용하게사용될수있을것으로생각된다. 일반적인화농성간농양은대부분세균에의한감염으로 4-6주간의항생제치료와함께농양의크기와개수, 배농상태에따라바늘천자, 경피경간배농, 수술적배농등을고려해야한다. 그에비해톡소카라증에의한간농양은항생제및배농치료가필요없고경구약을 5일간복용함으로써치료가종결된다. Sturchler 등 [23] 에따르면톡소카라증에대한 albendazole 치료의임상적효과는환자의약 47% 에서나타난다고하였지만본연구에서는 albendazole 투여후 92% 에서좋은치료반응을나타내어 albendazole을간농양으로발현된톡소카라증의 1차치료약제로사용할수있을것으로생각된다. 따라서호산구증가증을동반한간농양환자에서조기에톡소카라항체를포함한혈청검사가시행된다면진단및치료에도움을줄수있을것이다. 본연구는후향적연구이며, 대상환자수가적고, 톡소카라증진단에있어 ELISA 의위양성가능성때문에제한점이있다. 육회나채소생식이흔한우리나라의음식문화를고려해볼때톡소카라증의유병률이증가할것으로예상되며향후톡소카라증에대한더많은연구가필요할것이다
5 - 주동욱외 5 인. 간농양으로발현된톡소카라증 - 요 목적 : 성인에서간농양으로발현된톡소카라증환자들을분석하여임상양상, 검사소견, 치료및경과를알아보고자하였다. 방법 : 2008년 1월부터 2011년 7월까지톡소카라증에의한간농양환자 14명을후향적으로분석하였다. 환자들의증상, 직업력, 식습관, 애완동물접촉여부, 알레르기질환유무, 말초혈액호산구수, 혈청 IgE, 다른장기의동반침범유무등을조사하였다. Albendazole 치료후 CT, 말초혈액호산구수, 혈청 IgE를추적검사하여반응을평가하였다. 결과 : 총 568명의간농양환자중 14명 (2.5%) 에서톡소카라증에의한간농양으로진단되었으며남자가 9명, 여자가 5명이었다. 우상복부또는심와부통증이 4예 (28.6%), 기침 1예가있었고나머지 9예 (64.3%) 에서는특이증상이없었다. 폐침범이 5예 (35.7%), 대장침범이 1예 (7.1%) 있었으며, 6예 (42.9%) 에서소의육회나간을생식한과거력이있었다. 직업력, 알레르기병력에서는특이사항이없었으며애완동물과접촉한경우도없었다. 내원초기혈액검사에서호산구수와 IgE는모두상승되어있었고초기복부 CT에서는단일또는다발성의경계가불분명한저음영병변이관찰되었다. Albendazole 치료 1개월후호산구수는대부분 (93%) 정상화또는감소되었으나 IgE는다양한반응을보였다. CT에서관찰되었던간농양은치료 6개월내에대부분 (92%) 의환자에서소실되었다. 결론 : 톡소카라증에의한간농양은일반적인화농성간농양과는임상양상, 검사소견, 치료등에서차이점을보인다. 호산구증가증을동반한간농양환자에서조기에톡소카라항체를포함한혈청검사가시행된다면진단및치료에도움을줄수있을것이다. 중심단어 : 톡소카라증 ; 간농양 약 REFERENCES 1. Morris PD, Katerndahl DA. Human toxocariasis: review with report of a probable case. Postgrad Med 1987;81: Despommier D. Toxocariasis: clinical aspects, epidemiology, medical ecology, and molecular aspects. Clin Microbiol Rev 2003;16: Van Assendelft OW. Reference values for the total and differential leukocyte count. Blood Cells 1985;11: Beaver PC, Snyder CH, Carrera GM, Dent JH, Lafferty JW. Chronic eosinophilia due to visceral larva migrans: report of three cases. Pediatrics 1952;9: Park HY, Lee SU, Huh S, Kong Y, Magnaval JF. A seroepidemiological survey for toxocariasis in apparently healthy residents in Gangwon-do, Korea. Korean J Parasitol 2002;40: Dent JH, Nichols RL, Beaver PC, Carrera GM, Staggers RJ. Visceral larva migrans: with a case report. Am J Pathol 1956;32: Kim YJ, Kyung SY, An CH, et al. The characteristics of eosinophilc lung diseases cause by toxocara canis larval infestation. Tuberc Respir Dis 2007;62: Huang CJ, Pitt HA, Lipsett PA, et al. Pyogenic hepatic abscess: changing trends over 42 years. Ann Surg 1996;223: Rahimian J, Wilson T, Oram V, Holzman RS. Pyogenic liver abscess: recent trends in etiology and mortality. Clin Infect Dis 2004;39: Pawlowski Z. Toxocariasis in humans: clinical expression and treatment dilemma. J Helminthol 2001;75: Lim JH. Toxocariasis of the liver: visceral larva migrans. Abdom Imaging 2008;33: Saporito L, Scarlata F, Colomba C, Infurnari L, Giordano S, Titone L. Human toxocariasis: a report of nine cases. Acta Paediatr 2008;97: Shin YM. Hepatic eosinophilic abscess presenting as a single nodular mass. Korean J Hepatol 2010;16: Inoue K, Inoue Y, Arai T, et al. Chronic eosinophilic pneumonia due to visceral larva migrans. Intern Med 2002; 41: Roig J, Romeu J, Riera C, Texido A, Domingo C, Morera J. Acute eosinophilic pneumonia due to toxocariasis with bronchoalveolar lavage findings. Chest 1992;102: Jacob CM, Pastorino AC, Peres BA, Mello EO, Okay Y, Oselka GW. Clinical and laboratorial features of visceral toxocariasis in infancy. Rev Inst Med Trop Sao Paulo 1994; 36: Jacquier P, Gottstein B, Stingelin Y, Eckert J. Immunodiagnosis of toxocarosis in humans: evaluation of a new enzyme-linked immunosorbent assay kit. J Clin Microbiol 1991;29: Magnaval JF, Fabre R, Maurières P, Charlet JP, de Larrard B. Application of the western blotting procedure for the immunodiagnosis of human toxocariasis. Parasitol Res 1991; 77: Page AP, Rudin W, Fluri E, Blaxter ML, Maizels RM. Toxocara canis: a labile antigenic surface coat overlying the epicuticle of infective larvae. Exp Parasitol 1992;75:
6 - The Korean Journal of Medicine: Vol. 82, No. 4, Del Prete GF, De Carli M, Mastromauro C, et al. Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. J Clin Invest 1991;88: Magnaval JF, Glickman LT, Dorchies P, Morassin B. Highlights of human toxocariasis. Korean J Parasitol 2001; 39: Magnaval JF, Berry A, Fabre R, Morassin B. Eosinophil cationic protein as a possible marker of active human Toxocara infection. Allergy 2001;56: Stürchler D, Schubarth P, Gualzata M, Gottstein B, Oettli A. Thiabendazole vs. albendazole in treatment of toxocariasis: a clinical trial. Ann Trop Med Parasitol 1989;83: Magnaval JF. Comparative efficacy of diethylcarbamazine and mebendazole for the treatment of human toxocariasis. Parasitology 1995;110(Pt 5):
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