대한내과학회지 : 제 78 권제 4 호 2010 증례 09-168 간질환자에서 Vibrio cholerae non-o1 에의한화농근육염 전남대학교의과대학 1 감염내과, 2 진단검사의학교실 이경주 1 박경화 1 장희창 1 김성은 1 장미옥 1 정숙인 1 신종희 2 A case of pyomyositis caused by Vibrio cholerae non-o1 in a patient with liver Kyung Ju Lee, M.D. 1, Kyung Hwa Park, M.D. 1, Hee-Chang Jang, M.D. 1, Seong Eun Kim, M.D. 1, Mi Ok Jang, M.D. 1, Sook-In Jung, M.D. 1, and Jong-Hee Shin, M.D. 2 1 Division of Infectious Disease, 2 Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Korea Vibrio cholerae non-o1 mainly causes gastroenteritis and rarely causes extraintestinal infections, such as bacteremia. Skin and soft tissue infections are also possible, but the incidence rate is very low. Although the most common cause of pyomyositis is Staphylococcus aureus, Gram-negative organisms such as Vibrio species may also cause pyomyositis in patients with chronic liver disease. Pyomyositis caused by Vibrio cholerae non-o1 has not been reported in Korea. Here, we report a case of pyomyositis caused by V. cholerae non-o1 bacteremia in a patient with liver following seafood exposure. This case study suggests that V. cholerae, as well as V. vulnificus, should be considered when soft tissue infections occur in patients with liver after seafood exposure. In addition, physicians should consider imaging studies for a prompt diagnosis if the patient complains of severe pain disproportionate to the skin manifestation. (Korean J Med 78:518-522, 2010) Key Words: Liver ; Pyomyositis; Vibrio cholerae non-o1 서론 Vibrio 균속에는 35종이상의균종이속해있으며이중 1/3 정도가인체감염을일으키는것으로알려져있다. 임상검체에서가장흔히분리되는 Vibrio 균종은 V. cholerae, V. parahaemolyticus, V. vulnificus 및 V. alginolyticus로서식생활과지역에따라우세하게분리되는균종이다르다 1). 이중 V. cholerae는세포표면의 O 항원에따라크게 V.cholerae O1, O139 와 non-o1로구분되며, O1, O139 는주로유행성의다량 의수양성설사를일으킨다. V. cholerae non-o1은경한위장관증상을일으키나이외에도면역저하자에서는기회감염균으로 V. vulnificus처럼장내감염에이차적으로중증감염을일으킬수있다 2,3). 그러나국내에서 V. cholerae non-o1, non- O139 에의한화농근육염에대하여아직까지보고된예가없다. 저자들은간경변환자에서해산물복용후 Vibrio cholerae non-o1 균혈증에동반되어속발성으로발생한화농성근염을진단하고치료한예를경험하였다. 이에저자들은 V. cholerae non-o1에의한화농근육염이발생한예를피부연 Received: 2009. 6. 8 Accepted: 2009. 9. 8 Correspondence to Kyung-Hwa Park, M.D., Department of Infectious Diseases, Chonnam National University Hospital, 8 Hak-dong, Dong-gu, Gwangju 501-757, Korea E-mail: medkid@dreamwiz.com - 518 -
- Kyung Ju Lee, et al. Pyomyositis due to V. cholera non-o1 - A B Figure 1. MRI of the right tibia and calf. (A) Coronal and (B) axial T2 images showing pyomyositis and deep fasciitis with necrosis or abscess formation in the soleus muscle. 조직감염으로보고된다른증례와함께비교하여보고하는바이다. 증례 B형간염에동반된간경변이있는 42세남자가발열과함께우측하지의통증으로내원하였다. 내원 3일전생선회를먹고다음날부터발열과수양성설사 (3회/ 일 ) 가발생하였고, 설사는호전되었으나내원 1일전우측하지의통증이발생하고부종이진행하여내원하였다. 활력징후는혈압 110/70 mm/hg, 맥박수 78회 / 분, 체온 38.5, 호흡수는 20회 / 분이었다. 신체검사상급성병색을보였으며의식은명료하였다. 공막에황달이관찰되었고, 우측하지에약간의발적에동반된부종이있었으나피부에상처나수포등은관찰되지않았다. 종아리촉진시압통을호소하였고, 복부진찰에서팽만이나압통은없었다. 검사실소견으로일반혈액검사는백혈구 5,400/mm 3 ( 분엽중성구 91.7%, 임파구 4.4%), 혈색소 14.0 g/dl, 혈소판수 35,000/ mm 3 이었고, 생화학검사는 AST 38 U/L, ALT 20 U/L, total bilirubin 2.14 mg/dl, 총단백 6.5 g/dl, 알부민 3.6 g/dl, BUN 9.5 mg/dl, creatinine 0.7 mg/dl, LDH 438 U/L, creatinine kinase 71 U/L 이었다. 혈액응고검사는 PT 15.2 (1.35, INR), aptt 63.8초로증가되어있었다. 요검사상 ph 5.0, Protein 30 mg/ dl, WBC 2+ 였고, 대변검사에서염증세포는관찰되지않았다. 말초혈관에서 2쌍의혈액배양을시행하였고, Vibrio vulnificus 에의한패혈증의심하에 cefotaxime 과 doxycycline 병합요법을시작하였다. 제2병일째우측다리에피부의변화는없이부종과통증 이악화되어우측경골부자기공명영상 (Rt tibia and calf MRI) 을촬영하였다. 가자미근육 (soleus muscle) 주위근막의조영증강소견과함께가자미근육은 T2 강조영상에서전반적으로증가된신호강도를보이면서조영제주입후에는조영증강이부분적으로되지않는소견으로괴사가동반된근육염이있었다 ( 그림 1). 화농근육염과근막염을진단하고항생제치료를지속하였으나발열과다리의부종과통증이악화되어내원 4일째근막절개술을시행하였다. 수술시시행한조직의배양에서균은동정되지않았지만내원시시행한혈액배양에서그람음성간균이배양됨을확인하였다. 이균은 TIBS 배지에서노란집락을형성하면서 O1, O139 항혈청검사에응집하지않는 Vibrio cholearae non-o1로확정되었고, 자동화기기 (VITEK 2) 를이용한항생제감수성검사에서는 ampicillin과 trimethoprim-sulfamethoxazole, cefotaxime, ciprofloxacine에모두감수성이었고, 디스크확산법을이용하여시행한 tetracycline, chlorampenicol에도모두감수성이었다. 이후항생제치료를지속하였고, 환자의발열과통증은점차호전되었으며, 입원 19일째수술부위에피부이식술 (local advancement flap) 을시행하였다. 입원 40일째 1일 2회경구 ciprofloxacin 500 mg으로유지하여퇴원하였고, 외래에서 3개월째추적시행한하지컴퓨터촬영에서근육내농양은더이상관찰되지않았다. 고찰근육은병원체의침범에강한저항성을가진조직으로알려져있어감염성근육염은흔치않은질환이다. 근육을침범한세균의종류에따라화농근육염, 가스괴저, 비clostridial - 519 -
- 대한내과학회지 : 제 78 권제 4 호통권제 596 호 2010 - Table 1. Cases of skin and soft tissue infections caused by Vibrio cholerae non-o1 Reference Age/Sex Seafood exposure Culture 15 54/F (-) Blood, bulla aspirate 16 75/M (-) Bulla aspirate 17 51/M (-) but had eaten duck Blood, wound Underlying disease HSCT Liver Liver This case 42/M Raw fish Blood Liver HSCT, hematopoietic stem cell transplantation; N/A, not available. Manifestation Hemorrhagic bullous skin lesion with erythema in right leg Painful bulla on right foot and ankle Diarrhea, bulla on both legs, and a necrotic skin lesion Diarrhea and painful swelling in right leg Treatment (antibiotics vs. surgery) Outcome N/A Death Antibiotics+debridement of necrotic tissue Ceftazidime+doxycyline Cefotaxime+doxycyline Fasciotomy Recovery Death Recovery 근육염등으로구분하며, 이중화농근육염은주로황색포도알균에의해발생하고간혹폐렴알균또는그람음성창자막대균에의해서도발생한다 4). 화농근육염은세균이인접한부위의피부및연조직의농양이나욕창, 궤양, 관통상으로부터근육에전파되거나다른부위에서발생한균혈증으로세균이근육에파종되어근육염이발생할수있다 5). 본증례는 V. cholerae non- O1 균혈증에속발성으로화농근육염, 근막염이발생한경우로, 국내에서 V. cholerae non-o1, non-o139에의한피부연조직감염이드물게보고되었지만화농근육염이동반된경우는외국문헌에서면역저하환자에서화농근육염으로보고된사례에이어국내에서처음으로보고한다 6). V. cholerae의분류는 V. cholerae 항혈청 O1에대한응집유무에따라 O1과 non-o1으로분류하였으나인도에서유행성콜레라를일으켰던 V. cholerae O139 혈청형이발견된이후로 V. cholerae를 O1, O139, non-o1 혈청형으로구분하고있다 7). V. cholerae non-o1은주로유행성의심한수양성설사를일으키는 V. cholerae O1과는달리산발적으로발생하며, 특별한치료없이회복되는장염이대부분이다 7,8). 또한장내감염뿐만아니라복수액, 척수액, 귀, 창상, 및담낭등의장외감염을유발할수있고패혈증을일으킬수있다 3,9). V. cholerae non-o1가균혈증을일으키는기전과요인에대해서정확히밝혀지지않았으나콜레라유사독소 (choleralike enterotoxin), 세포독소 (cytotoxin) 와용혈독소 (E1-Tor-like hemolysin) 등을분비하고균자체에협막이있어인체의방어기전을피할수있는것으로생각되어지고있다 9). 대부분간경변이나당뇨병, 혈액질환등의만성질환을가지거나면역이억제되어있는환자에서균혈증이발생하는데면역상 태에따라기회감염균으로작용한다. 이런장외감염중피부와연부조직감염이동반된경우, 표 1을보면국내에지금까지 3예보고되었는데 10-12), 모두면역저하자에서발생하였고, 피부의발적, 수포, 궤양이동반되어 V. vulnificus에의한괴사성근막염과유사한피부병변을보였다. 본증례는수포, 출혈반, 궤양등의비브리오패혈증에서흔히볼수있는피부병변은동반되지않으면서화농근육염이발생하였다. 화농근육염은본증례처럼초기에광범위한근육의통증과열감이발생하나감염이근육의심부에위치하여피부의발적은잘나타나지않으므로진단이지연될수있다. 임상적으로비브리오패혈증에서자주보이는피부병변이없다하더라도화농근육염이합병증으로발생할수있으므로 V. cholerae non-o1 균혈증에사지의부종, 통증이동반된경우 MRI 등을통한적극적인진단이필요하겠다. V. cholerae non-o1 에의한감염의임상양상은피부연조직감염이외에도다양하게보고되고있다 13). 현재까지 V. cholerae non-o1 패혈증으로인한안구내염, 뇌염이보고되었고 14,15), 폐렴및요로감염도보고되어 V. cholerae non-o1 의장외감염양상이다양해지고있다 16,17). 면역억제제등의사용으로인한면역저하자가늘어나고국내처럼만성간질환자가많은지역에서는 V. vulnificus를포함한다양한 Vibrio 균종에의한감염증이발생할수있으므로 18), 균의정확한동정이필요하고균에따라가능한임상양상에대하여알아야할것이다. 화농근육염의치료는항생제정맥주사와배농이다. 초기항생제의선택은다양할수있으나면역저하자의경우에서는이증례에서보듯이그람음성균이고려되어야하고 3~4 주이상의항생제정맥투여가필요하다. 본증례는심부근 - 520 -
- 이경주외 6 인. Non-O1/O139 Vibrio cholerae 에의한화농성근염 - 막염에대하여는근막절개술을시행하였으나화농근육염은배농술없이항생제치료만으로호전되었다. 하지만형성된농양이큰경우는수술적혹은영상의학적중재술을이용한배농을통하여항생제기간을단축시킬수있다. V. cholerae non-o1 감염에서균혈증이발생한후치료가늦어지는경우에는 60% 이상의사망률을보이며예후가좋지않다고알려져있다 9). 국내에서보고된 V. cholerae non-o1에의한피부와연부조직감염을보고한기존의 3예중 2예는사망하여 50% 이상의사망률을보였다. 그러므로연부조직감염이동반된경우에는빠른진단과함께근막절개술, 괴사조직제거와같은수술적치료가함께시행되어야한다. 결론적으로, 저자들은만성간질환이있는환자에서설사후피부병변은없었지만지속되는하지의통증과부종으로 MRI를촬영하여근육내의괴사를동반한화농근육염과심부근막의근막염을진단할수있었고, 만성간질환자와같은면역저하자에서는해산물섭취력이있는경우 V. cholerae non-o1를포함한다양한 Vibrio 감염증을고려해보아야하겠다. 요약 V. cholerae non-o1은위장관염또는균혈증을발생시키고, 매우드물게피부및연부조직감염을일으킨다. 화농근육염은황색포도알균이가장흔한균으로알려져있으나, 만성간질환자에서는비브리오균같은그람음성균에의한화농근육염이발생할수있다. 이에저자들은간경변이있는환자에서여름철에어패류생식후 V. cholerae non-o1에의한화농근육염이발생하여초기에진단후회복된예를국내처음으로경험하였기에이를보고하는바이다. 간경변증환자에서해산물또는바닷물에노출된후발생한피부및연부조직감염의경우 V. vulnificus뿐만아니라 V. cholerae에의한감염도고려해야한다. 또한임상적으로비브리오패혈증에서자주보이는피부병변이없다하더라도화농근육염이합병증으로발생할수있으므로, V. cholerae non-o1 균혈증에사지의부종, 통증이동반된경우 MRI 등을통한적극적인진단을해야한다. 중심단어 : 간경변 ; 화농근육염 ; Vibrio cholerae non-o1 REFERENCES 1) Janda JM, Powers C, Bryant RG, Abott SL. Current perspective on the epidemiology and pathogenesis of clinically significant Vibrio spp. Clin Microbiol Rev 1:245-267, 1988 2) Morris JG Jr. Non-O group 1 Vibrio cholerae: a look at the epidemiology of an occasional pathogen. Epidemiol Rev 12:179-191, 1990 3) Kaper JB, Morris JG Jr, Levine MM. Cholera. Clin Microbiol Rev 8:48-86, 1995 4) Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger P, Goldstein EJ, Gorbach SL, Hirsch mann JV, Kaplan EL, Montoya JG, Wode JC. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 41:1373-1406, 2005 5) Crum NF. Bacterial pyomyositis in the United States. Am J Med 117:420-428, 2004 6) Couzigou C, Lacombe K, Girard PM, Vittecoq D, Meynard JL. Non-O:1 and non-o:139 Vibrio cholerae septicemia and pyomyositis in an immunodeficient traveler returning from Tunisia. Travel Med Infect Dis 5:44-46, 2007 7) Tison DL. Vibrio. In: Murray PR, Baron EJ, eds. Manual of clinical microbiology. 7th ed. p. 497-505, Washington DC, American Socieity for Microbiology, 1999 8) Uh Y, Jeoung AS, Jang IH, Yoon KJ, Lee HY. A case of Vibrio cholerae non-o1/o139 gastroenteritis. Korean J Clin Pathol 21:49-52, 2001 9) Safrin S, Morris JG Jr, Adams M, Pons V, Jacobs R, Conte JE Jr. Non-O:1 Vibrio cholerae bacteremia: case report and review. Rev Infect Dis 10:1012-1017, 1988 10) Choi SM, Lee DG, Kim MS, Park YH, Kim YJ, Lee S, Kim HJ, Choi JH, Yoo JH, Kim DW, Min WS, Shin WS, Kim CC. Bacteremic cellulitis caused by non-o1, non-o139 Vibrio cholerae in a patient following hematopoietic stem cell transplantation. Bone Marrow Transplant 31:1181-1182, 2003 11) Uhm JS, Oh BS, Lee SH, Kim SI, Kim YR, Park YJ, Kang MW. A case of skin and soft tissue infection caused by Non-O1, non-o139 Vibrio cholera in a patient with liver. Infect Chemother 37:104-106, 2005 12) Yang WI, Park SM, Kim YJ, Kim JM, Choi JY, Kang EW, Huh AJ. Necrotizing fasciitis and sepsis due to Vibrio cholerae in a patient with liver. Korean J Med 74:131-134, 2008 13) Blake PA, Weaver RE, Hollis DG. Diseases of humans (other than cholerae) caused by vibrios. Annu Rev Microbiol 34:341-367, 1980 14) Yang CC, Lee BJ, Yang SS, Lin YH, Lee YL. A case of non-o1 and non-o139 Vibrio choleree septicemia with endophthalmitis in a cirrhotic patient. Jpn J Infect Dis 61:475-476, 2008 15) Suankratay C, Phantumchinda K, Tachawiboonsak W, Wilde H. Non-serogroup O:1 Vibrio cholerae bacteremia and cerebritis. - 521 -
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