Case Report J Korean Geriatr Soc 2014;18(2): 혈액투석환자에서혈행을통한파종성감염으로발생한칸디다관절염 1 예 국립중앙의료원내과 1, 정형외과 2 박수

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1 Case Report J Korean Geriatr Soc 2014;18(2): 혈액투석환자에서혈행을통한파종성감염으로발생한칸디다관절염 1 예 국립중앙의료원내과 1, 정형외과 2 박수연 1 권용환 1 김석원 1 장동원 1 정연오 1 손민수 2 차란희 1 Candida Arthritis in a Hemodialysis Patient Soo Yeon Park, MD 1, Yong Hwan Kwon, MD 1, Seok Won Kim, MD 1, Dong Won Jang, MD 1, Yeon Oh Jung, MD 1, Min Soo Shon, MD 2, Ran-Hui Cha, MD 1 Departments of 1 Internal Medicine and 2 Orthopedic Surgery, National Medical Center, Seoul, Korea Candida is a rare cause of infectious arthritis, and it can be found in infants and immunocompromised patients. Patients with maintenance hemodialysis are prone to opportunistic infections because of altered immunity, and frequent exposures to health-care associated infections. Herein, we report a case of candida arthritis of right shoulder with preceding fungemia in patients with maintenance hemodialysis. The diagnosis is based on the isolation of Candida Tropicalis from blood and synovial fluids of the shoulder joint. The patient has received intravenous fluconazole and arthroscopic surgical debridement. We then changed the fluconazole into amphotericin B due to the abnormal signs in the liver function tests, although the fluconazole successfully controlled fungemia and arthritis. To the best of our knowledge, this is the first case of candida arthritis in patients with maintenance hemodialysis in South Korea. Key Words: Arthritis, Candida, Fungemia, Hemodialysis 서 진균에의한감염성관절염은매우드문질환이다. 병소에서진균이동정되는경우를제외하고, 분명한원인이있고명백한감염증상이보여도진균에의한감염성관절염으로진단되는경우는드물다. 진균에의한관절염은대부분혈행을통한파종성감염이며, 특히칸디다에의한경우는인공관절물의삽입이나관절내주사로인한직접침입으로인해발생 론 Received: December 30, 2013 Revised: February 20, 2014 Accepted: February 20, 2014 Address for correspondence: Ran Hui Cha, MD Department of Internal Medicine, National Medical Center, 245 Eulji-ro, Jung-gu, Seoul , Korea Tel: , Fax: reginaprayer@gmail.com 한다 1). 칸디다관절염은주로신생아나면역저하자에서발생하는질환으로정상면역을가진성인에서는발생이드물다 2). 성인에서발생하는경우는장기간의항생제또는스테로이드의사용, 정맥내도관, 혈액투석, 정맥주사남용등의위험인자가있는경우이다 1). 혈액투석중인말기신부전환자에서발생한칸디다관절염은해외에서 2예가보고된적이있었으나, 국내에서는보고된바가없다 3). 저자들은혈액투석환자에서파종성진균감염에동반된칸디다관절염증례를경험하였기에문헌고찰과함께보고하는바이다. 증례 환자는 66 세남자로고혈압의기왕력이있으며, 20 년전두개 Copyright 2014 Korean Geriatric Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (

2 Soo Yeon Park, et al: Candida Arthritis on HD Patient Fig. 1. Noncontrast magnetic resonance imaging of left shoulder. (A) T2- and (B) T1-weighted coronal-oblique images demonstrate fluid collection (arrows) surrounded by thick band-like sac (due to extensive and hypertrophic bursitis) in subacromial-subdeltoid bursa and the presence of abnormal soft tissues/muscle signals. Magnetic resonance images also show a large bone erosion (arrowhead) (defined as well-demarcated osseous lesion with disruption of the normal cortical contour) and coarse signal changes with irregular margins which are considered as reactive marrow edema in (asterisk) the humeral head and glenoid. All of these findings are consistent with the diagnosis of infectious arthritis. 내출혈로우측근력저하를동반하였다. 16년전말기신부전을진단받고혈액투석중이었다 년우측대퇴골골절로양극성인공관절부분치환술 (bipolar hemiarthroplasty) 을받았던기왕력이있었다 년 10월사고로삽입물주위골절 (periprosthetic fracture) 이발생하여정형외과에입원하여인공고관절재치환수술 (revision total hip arthroplasty) 을시행받았다. 경험적항생제로정주 cefotetan 1 g을 8시간마다, ciprofloxacin 200 mg을 12시간마다정주하였다. 수술후 10 일째활력징후는체온 38, 혈압 146/71 mmhg, 심박수 95회 /min 이었으며, 환자의수술부위에발적이나부종등의감염소견은없었다. 일반혈액검사에서백혈구 8,600/μL( 중성구 80.6%), 혈색소 10.2 g/dl, 혈소판 96,000/ μl, C-반응성단백 104 mg/l 였다. 단순흉부 X-선검사와심전도는정상소견을보였다. 정주 piperacillin-tazobactam 2.25 g을 8시간마다투여하는것으로항생제를변경하였으나, 수술후 14일째체온 38 로발열이지속되며활력징후는혈압 79/56 mmhg, 심박수 152 회 /min 으로불안정하였다. 발열이발생한수술후 10일째시행한혈액배양검사 3쌍중 3쌍에서 Candida tropicalis 가동정되었고, 우측에유치되었던중심정맥카테터말단부배양에서도칸디다종이동정되었다. 환자는칸디다진균혈증으로진단되었고, 수술후 14일째정주 fluconazole 치료를받기시작하였다. 진균항생제감수성검사에서 C. tropicalis 는 fluconazole, amphotericin B, ketoconazole 에감수성을보였다. fluconazole 치료 7일후시행한혈액배양검사에서칸디다는음전되었고, 다른균주는동정되지않아정주항생제 piperacillin-tazobactam은중단하였다. fluconazole 치료 12일째활력징후는체온 37.4, 혈압 140/80 mmhg, 심박수 75회 /min 으로호전되는소견을보였으나, 통증과부종을동반한좌측견관절움직임의제한이관찰되었다. 정형외과협진하시행한어깨관절 X-선검사및자기공명영상에서견봉하및삼각근하와부리돌기밑점액낭의비균질한삼출액증가소견과활액막의염증과함께비후가관찰되었다. 또한관절와상완관절 (Glenohumeral joint space) 주변의연부조직과근육및상완골골두 (humeral head) 와관절와 (glenoid) 의염증소견을보이고있어아급성감염성관절염이의심되었다 (Figs 1, 2). 이후시행한초음파 94 J Korean Geriatr Soc 18(2) June 2014

박수연외 : 혈액투석환자에서발생한칸디다관절염 하관절활액배양검사결과혈액배양검사에서와동일한칸디다종이동정되었다. 다른장기감염증의감별진단을위하여시행한심초음파결과 vegetation 의증거는없었다. 안저검사 Fig. 2. Noncontrast magnetic resonance imaging of left shoulder.

상망막중심부특이소견은보이지않았으며, 망막주변부는환자의협조가어려워관찰하지못하였다. 진균성관절염진단후관절경하외과적변연절제술을시행하였다 (Fig. 3). 수술조직의배양에서도활액과동일한칸디다종이동정되었다. 어깨관절수술후 6일째수술부위의통증과부종은감소되었으나발열이재발하였고, 총빌리루빈 23.

3 박수연외 : 혈액투석환자에서발생한칸디다관절염 하관절활액배양검사결과혈액배양검사에서와동일한칸디다종이동정되었다. 다른장기감염증의감별진단을위하여시행한심초음파결과 vegetation 의증거는없었다. 안저검사 Fig. 2. Noncontrast magnetic resonance imaging of left shoulder. (A) Axial and (B) sagittal oblique images show synovial inflammatory proliferations as well as joint effusion in the glenohumeral joint, which are compatible with septic arthritis. 상망막중심부특이소견은보이지않았으며, 망막주변부는환자의협조가어려워관찰하지못하였다. 진균성관절염진단후관절경하외과적변연절제술을시행하였다 (Fig. 3). 수술조직의배양에서도활액과동일한칸디다종이동정되었다. 어깨관절수술후 6일째수술부위의통증과부종은감소되었으나발열이재발하였고, 총빌리루빈 23.6 mg/dl, aspartate aminotransferase 83 U/L, alanine aminotransferase 12 U/L, activated partial thromboplastin time 78.7 seconds prothrombin time (international normalized ratio) 2.36 소견으로간기능부전이발생하였다. 간부전의발생으로항진균제는 fluconazole 에서 amphotericin B로변경하였다. 당시시행한복부컴퓨터단층촬영에서간내칸디다감염을의심할만한소견은보이지않았고, 만성간질환에합당한소견을보였다. 혈액배양검사는지속적으로칸디다음전상태를보였으며, 관절염부위에서수술후 10일째시행한배양검사에서도칸디다는음전된결과를보였다 (Fig. 4). 관절경하변연절제술 (arthroscopic surgical debridement) 시행후국소감염은호전되는양상이었으나, 수술직후 bilirubin 의급격한상승, 항진균제의변경후에도호전을보이지않는양상과영상소견으로미루어보아허혈성간염으로의심되는간기능부전으로보존적치료를시험하였으나환자는사망하였다. Fig. 3. Arthroscopic image showing (A) red mucous fluid in the glenohumeral joint. This fluid is also being identified in the subacromial space. (B, C) Arthroscopic images of severe hypertrophic synovitis of intraarticular capsule, and (D) articular erosion and detachment of the humeral head and glenoid. Parts of the subchondral bone are exposed. Arthroscopic images of (E) extensive bursitis with thick and hyperemic subacromialsubdeltoid bursa and (F) abnormal soft tissue quality in the subacromial space. J Korean Geriatr Soc 18(2) June

4 Soo Yeon Park, et al: Candida Arthritis on HD Patient Fig. 4. Flowchart showing clinical events, interventions, and the level of C-reactive proteins. 고찰 2011년현재우리나라에서인구백만명당 1,224.8명이말기신부전이며, 환자의 67.2% 가혈액투석을시행받고있다 4). 혈액투석환자는몇가지이유로감염에취약하게된다 5). 첫째, 말기신부전환자는세포면역 (cellular immunity), 호중구기능 (neutrophil function), 보체활성 (complement activation) 이손상되어감염원에대하여취약하게된다. 둘째, 혈액투석과정에서장시간혈관접근경로가노출되어감염원이전염될기회가반복적으로발생한다. 셋째, 혈액투석환자는빈번한입원과수술이요구되는경우가많아의료관련감염에노출될기회가많아진다. 감염은혈액투석환자에서 23.1% 로 3번째로흔한사망원인이다 4). 가장흔한감염은혈관접근경로의감염이지만, 이는전체감염의 1/3에해당할뿐밝혀지지않은병소의감염도상당부분을차지하고있다. 혈액투석환자에서감염성관절염또한균혈증의증가로그발생빈도가늘어나고있다. 감염성관절염에서진균은드문감염원이며, Coccidiomycosis, Blastomycosis, Sporotrichosis, Candida 등이관절염을일으킬수있다 6). 이중말기신부전환자에서감염성관절염을일으키는진균은칸디다가유일하게보고되었다 3). 현재까지말기신부전환자에서발생한감염성관절염 은 40예의증례가보고된적이있으며, 이중칸디다에의한것은 3예에불과하다. 칸디다종은침습성진균감염의가장흔한원인으로대부분의장기를침범할수있으며, 비침습성인피부진균증부터침습성진균감염까지다양한범위의질병을일으킬수있다. 칸디다감염의흔한위험인자는광범위항생제의사용, 중심정맥관사용, 집중치료실 ( 중환자실 ) 에서혈액투석을받은경우, 인공삽입물을가지고있는백혈구감소증환자, 면역억제제치료 ( 스테로이드, 항암화학요법, 면역조절제 ) 등이다 6). 칸디다에의한관절염은드문질환으로발병률은알려져있지않다. 하지만다른부위의칸디다감염증이증가함에따라칸디다관절염의빈도또한증가할것으로추측된다. 칸디다종중관절염을일으키는것은 C. albicans, C. glabrata, C. guilliermondii, C. Krusei, C. parapsilosis, C. tropicalis, C. zeylanoides로알려져있다 6). 침범되는관절은대부분체중부하를받는곳으로슬관절이가장많고, 그외에고관절, 견관절의순으로많으며발목관절, 주관절과손목관절에서의발생도보고되었다 7). 칸디다관절염의임상증상은다른세균성관절염과유사하며국소적인발적과동통, 발열이있으며운동의제한을보인다. 관절활액의백혈구수는수천에서수만까지다양하며, 다형백혈구의수가증가되어있어세균성감염과구분하기어려우며, 활액배양에서양성을보이는경우 96 J Korean Geriatr Soc 18(2) June 2014

5 박수연외 : 혈액투석환자에서발생한칸디다관절염 진단할수있다 8). 칸디다관절염은혈액성파종에의한것이가장흔한병태생리이지만, 대부분의경우에서칸디다관절염은뒤늦게진단된다. 혈액배양검사에서칸디다가확인된후 12일에서 7주가지나야증상이발생하기때문이다 9). 본증례는인공삽입물수술후장기간항생제를사용하였고, 혈액투석으로빈번한혈관접근을하였으며, 중심정맥관을거치하고있었고, 말기신부전으로면역력이저하되어진균감염의몇가지위험인자를가지고있었다. 칸디다혈증으로 fluconazole 을사용하여균음전상태를이루었음에도혈행성파종에의해칸디다관절염이병발하였을것으로생각된다. 기존에정상면역인의일시적인칸디다혈증의경우감염의원발부위를제거하고항진균제의사용은꼭필요치않다고했으나, 현재는정상면역의성인에서도칸디다혈증은 fluconazole 이나 echinocandin 으로치료하도록권고하고있다 10). 칸디다감염성관절염은 amphotericin B 정맥주사와배액으로임상적, 미생물학적으로 90% 의완치율을보여표준치료로이용되어왔다 9). 최근에는 amphotericin B 관련신독성등의부작용으로인하여 fluconazole 또한사용될수있으며, 6주간의정맥주사치료와이후 2주간 fluconazole 경구약제를유지할것을권고하고있다. 약물치료와더불어모든경우수술적인변연절제술을시행할것을권고하며, 관절경을이용한치료를선호한다 10). 본증례는칸디다혈증으로 fluconazole 치료를지속하던환자로병발한칸디다관절염에대하여관절경하변연절제술 (artheroscopic surgical debridement) 을시행하였다. 수술후발생한간부전으로 amphotericin B로변경투약하여진균혈증및관절내국소감염은호전양상을보였다. REFERENCES 1. Bariola JR, Saccente M. Candida lusitaniae septic arthritis: case report and review of the literature. Diagn Microbiol Infect Dis 2008;61: Lim KB, Kwak YG, Kim YS, Park KR. Shoulder joint infectious arthritis and acromioclavicular joint osteomyelitis due to Candida. Ann Rehabil Med 2012;36: Kathresal A, Biundo J, Blais CM, Morse S, Reisin E. A rare case of Candida arthritis in a hemodialysis patient. Am J Med Sci 2008;336: ESRD Registry Committee, Korean Society of Nephrology. Current renal replacement therapy in Korea: Insan Memorial Dialysis Registry, In: Proceedings of the 32nd Annual Autumn Meeting of the Korean Society of Nephrology; 2012 Nov 13; Gyungju. Korea; Seoul: Korean Society of Nephrology; 2012:2; Arduino MJ, Patel PR, Thompson ND, Favero MS. Hemodialysis-associated infections. In: Himmelfarb J, Sayegh MH, editors. Chronic kidney disease, dialysis, and transplantation: companion to Brenner & Rector s the kidney. 3rd ed. Philadelphia: Elsevier Inc.; p Kemper CA, Deresinski SC. Fungal infections of bone and joint. In: Anaissie EJ, McGinnis MR, Pfaller MA, editors. Clinical mycology. 2nd ed. [Edinburgh]: Elsevier Inc.; p Hansen BL, Andersen K. Fungal arthritis: a review. Scand J Rheumatol 1995;24: Cha HS, Lee YJ, Kang SW, Lee EB, Baek HJ, Han CW, et al. A case of Candida arthritis in chronic tophaceous gout. Korean J Med 1998;54: Murray HW, Fialk MA, Roberts RB. Candida arthritis: a manifestation of disseminated candidiasis. Am J Med 1976; 60: Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009;48: J Korean Geriatr Soc 18(2) June

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( ) Jkra076.hwp Vol. 11, No. 4, December, 2004 Objective: Ultrasonography (USG) of joints has a unique position for the diagnosis of joint diseases. Bone surface, cartilage, periarticular soft tissue and their pathologic