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1 대한내과학회지 : 제 89 권제 2 호 배양음성심내막염처럼발생한심장침범베체트병 1 예 울산대학교의과대학서울아산병원내과 윤희영 박신희 정수민 서유리 서보미 김성한 유빈 A Case of Cardiac Behçet s Disease Mimicking Culture-Negative Infective Endocarditis Hee-Young Yoon, Shin Hee Park, Soo Min Jeung, Yu ri Seo, Bo Mi Seo, Sung-Han Kim, and Bin Yoo Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Behçet s disease is an inflammatory disorder of unknown etiology with multi-organ involvement. Although it rarely involves the heart, once the heart is involved the results can be devastating. However, since cardiac involvement has various manifestations, diagnosis is challenging. The clinical features and echocardiographic findings of cardiac Behçet s may mimic culture-negative infective endocarditis. A correct diagnosis is usually made postoperatively. Here, we report the case of a 55-year-old male who was initially diagnosed with infective endocarditis that caused metastatic vertebral osteomyelitis. He underwent immediate cardiac surgery and received empirical antibiotics, but all culture findings were negative; however, he had a sustained fever and elevated inflammatory marker levels. After reviewing the results of pathologic and imaging studies, a final diagnosis of cardiac Behçet s disease was made. He was successfully treated with a high dose of corticosteroids. This report demonstrates a rare case of cardiac Behçet s disease mimicking culture-negative infective endocarditis. (Korean J Med 2015;89: ) Keywords: Behcet syndrome; Endocarditis; Spondylitis 서론베체트병 (Behcet s disease) 은원인미상의만성적이며여러기관을침범하는질병으로반복되는구강, 성기궤양, 안구침범, 피부병변을포함한여러가지임상증상으로발현한다 [1]. 베체트병의심장침범은매우드물고심내막염, 심 근경색, 좌심방동맥류, 대동맥판폐쇄부전증, 심장내혈전, 관상동맥질환등다양한임상증상으로발현한다. 특히심장침범베체트병에서는베체트병의진단기준이며첫진단시 90% 가량동반되는구강, 성기궤양동반없이발열, 흉통, 호흡곤란등비전형적인증상을호소하며내원하여진단에어려움이따른다 [2]. 저자들은배양음성심내막염으로진 Received: Revised: Accepted: Correspondence to Sung-Han Kim, M.D., Ph.D. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul , Korea Tel: , Fax: , shkimmd@amc.seoul.kr Copyright c 2015 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

- The Korean Journal of Medicine: Vol. 89, No. 2, 2015 - 단받고수술후치료중인환자에서최종적으로심장침범베체트병으로진단된증례를경험하였기에이를보고한다.

이후물리치료, 소침술등대증적치료를하며지내던중 1일전부터고열이동반되어응급실을방문하였다. 과거력 : 환자는 20년전폐결핵을진단받고완치받았으며평소복용중인약물은없었다. 이학적소견 : 내원당시활력징후는혈압 90/49 mmhg, 맥박 83회 / 분, 호흡수 20회 / 분, 체온 37.9 였고의식은명료하였다.

2 - The Korean Journal of Medicine: Vol. 89, No. 2, 단받고수술후치료중인환자에서최종적으로심장침범베체트병으로진단된증례를경험하였기에이를보고한다. 증례환자 : 55세남자주소 : 발열현병력 : 평소경미한허리통증을호소하였고, 3주전부터허리통증이악화되어한방병원에내원하여비조영증강허리자기공명영상 (nonenhanced L-spine magnetic resonance imaging [MRI]) 을시행후요추및경추추간판탈출증을진단받았다. 이후물리치료, 소침술등대증적치료를하며지내던중 1일전부터고열이동반되어응급실을방문하였다. 과거력 : 환자는 20년전폐결핵을진단받고완치받았으며평소복용중인약물은없었다. 이학적소견 : 내원당시활력징후는혈압 90/49 mmhg, 맥박 83회 / 분, 호흡수 20회 / 분, 체온 37.9 였고의식은명료하였다. 신체검사에서흉부청진에서호흡은깨끗하였고좌측 3-4 늑간에서 3도의확장기심잡음이청진되었다. 침을맞은부위에는피부감염증을의심할만한소견은없었고하부요추, 경추압통도없었다. 신경학적인검사에서양측하지의근력과감각은정상이었다. 혈액검사소견 : 내원시말초혈액검사에서백혈구수치가 12,500/mm 3 로증가되었고, 생화학검사에서 C-반응성단백질 (C-reactive protein, CRP) 이 mg/dl로상승되었다. 이외혈청생화학검사및혈액응고검사는모두정상범위였다. 방사선학적소견 : 흉부단순촬영검사에서이상소견없 었으며척추골수염을의심하여조영증강허리 MRI를시행하였고, T2 강조영상 (T2 weighted sequence) 에서고신호 (high signal) 의다발성병변이인접한경추 4, 5, 6번, 흉추 4, 5번, 요추 1, 2번척추에나타나화농성혹은척추골수염가능성이높을것으로생각하였다 (Fig. 1A and 1B). 심전도소견 : 분당 77회로동율동의 1도의방실차단 (1st A-V block) 이확인되었다. 치료및경과 : 입원 2일째항생제를사용하지않은상태에서요추 2번에대해컴퓨터단층촬영유도하뼈조직검사를시행하였고, 이후 2쌍의혈액배양후에경험적항생제로 cefazolin을투약하였다. 그러나발열이지속되고혈액및뼈조직에서배양되는균이없고, 뼈조직검사결과는만성염증이확인된것외그람염색, acid fast bacillus (AFB) 염색, periodic acid-schiff (PAS) 염색, 결핵균중합효소연쇄반응 (Mycobacterium tuberculosis complex polymerase chain reaction) 모두음성이었다. 입원 3일째심초음파를시행하였고, 대동맥판막폐쇄부전과승모판의증식증 (vegetation) 으로의심되는종괴가확인되어 (Fig. 2A and 2B) 응급수술을시행하였다. 수술장에서대동맥판의천공및승모판의염증, 좌심방천장을침범하는고름주머니와같은병변 (pus-sac like lesion) 과상행대동맥의부종성변화가확인되어모두절제하였고대동맥판막치환술및벤탈수술 (Bentall operation), 승모판판막치환술을시행하였다. 절제된조직에서그람, AFB 염색및균배양검사, 병리조직검사를시행하였고수술후지역사회획득감염성심내막염에준해항생제는 ampicillin, ceftriaxone 로변경하여투약하였다. 이후발열이지속되고수술장조직배양및 5일이상배양을연장한혈액검사에서배양된균이 A B Figure 1. T2-weighted magnetic resonance images of the whole spine were obtained. (A) The cervical and thoracic vertebrae image showed a change in the bone marrow signal and enhancement of the vertebral body with focal T2 high signal lesions at C4-5 and T4-5 (arrowheads). (B) The lumbar vertebrae image revealed a change in the bone marrow signal and enhancement of the vertebral bodies at L1-2 (arrowheads) with mild subligamentous spread at the anterior longitudinal ligament

- Hee-Young Yoon, et al. Cardiac Behçet s disease - B A Figure 2. Preoperative echocardiographic findings.

A periaortic echo-free space (arrow) in the aortic root with severe aortic regurgitation was demonstrated.

(A) The valves showed marked acute inflammation with microabscesses (arrow) and granulomatous tissues (hematoxylin and eosin [H&E] staining, 40).

(C) Mixed infiltrates of neutrophils, lymphohistiocytes, and plasma cells were present in the valvulitis (H&E staining, 200).

입원 17일째발열호전없고백혈구증가증및 CRP, 적혈구침강속도 (erythrocyte sedimentation rate, ESR) 의상승지속되어 doxycyclin을추가하였고발열은호전되었으나 CRP, ESR 상승은호전되지않았다. 이에대해결합조직질환과같은비감염성질환가능성을생각하여검사기록및임상경과를재검토하였다.

3 - Hee-Young Yoon, et al. Cardiac Behçet s disease - B A Figure 2. Preoperative echocardiographic findings. (A) Transthoracic echocardiography revealed redundant motion of the elongated aortic cusps (arrowhead), as seen in aneurysmal changes. A periaortic echo-free space (arrow) in the aortic root with severe aortic regurgitation was demonstrated. (B) The four-chamber view showed a vegetation-like mobile mass (arrow) involving the anterior mitral valve leaflet. A B C Figure 3. Histological findings of the aorta and aortic valves. (A) The valves showed marked acute inflammation with microabscesses (arrow) and granulomatous tissues (hematoxylin and eosin [H&E] staining, 40). (B) Extensive loss of the endothelial lining with fibrin deposition in the aortic valve (i.e., the red-painting sign ) was observed (arrows; H&E staining, 80). (C) Mixed infiltrates of neutrophils, lymphohistiocytes, and plasma cells were present in the valvulitis (H&E staining, 200). 없어, 배양음성심내막염가능성이높을것으로판단하고 Q 열 (Q fever), Bartonella에대한항체검사를추가로시행하였고 gentamicin, ampicillin/sulbactam 으로항생제를변경하였다. 입원 17일째발열호전없고백혈구증가증및 CRP, 적혈구침강속도 (erythrocyte sedimentation rate, ESR) 의상승지속되어 doxycyclin을추가하였고발열은호전되었으나 CRP, ESR 상승은호전되지않았다. 이에대해결합조직질환과같은비감염성질환가능성을생각하여검사기록및임상경과를재검토하였다. 이전감염성심내막염에서비특이적으로관찰될수있는판막염 (valvulitis) 으로생각한병리조직검사를재검토하였고, 판막에다수의미소농양 (microabscess) 및육아종조직 (granulation tissue) 이급성염증소견과함께확인되었고, 내피조직이광범위하게상실되고섬유소침착물로대체된베체트병에서특징적으로나타날수있는소견들을확인하였다 (Fig. 3A, 3B, and 3C). 또한, 그람염색, AFB 염색, PAS & silver 염색에서도확인된미생물이없었다. 심초음파 도첫진단당시대동맥판막이얇아져있으며대동맥판막에서승모판까지이어진결함 (defect) 이관찰되며, 증식증으로생각하는종괴가확인되어감염성심내막염에합당한소견이라판단하였으나재검토결과베체트병의심장침범시특징적으로나타날수있는대동맥판막의과잉성 (redundancy) 및무에코공간 (echo free space), 종괴와같은병변 (mass like lesion) 의가능성이높을것으로판단하였다 (Fig. 2A and 2B). 이러한소견들로베체트병의가능성이높을것으로판단하여베체트병의임상적증상과다른기관침범을확인하였고, 평소자주반복되는구강궤양외안과검진, 패설지반응 (pathergy test) 은모두음성으로확인되었고이외다른기관침범소견도뚜렷하지않았다. 이후반복되는균배양에배양되는균은없고 Q열, Bartonella 항체도모두음성으로확인되어배양음성심내막염보다는베체트병심장침범및척추침범의가능성이높을것으로판단하고입원 29일째프레드니솔론 30 mg 하루 2번투약을시작하였다. 이후입원 41일

4 - 대한내과학회지 : 제 89 권제 2 호통권제 660 호 째 CRP, ESR 정상화되었으며추가로시행한 human leukocyte antigen (HLA) 유형분류에서 HLA-B 51 양성이확인되었다. 수술후추적관찰한흉부심초음파에서판막및심장기능의이상없음을확인하였고입원 45일째추적관찰한조영증강허리자기공명영상에서경추 4-5번, 흉추 4-5번, 요추 1-2번골수및추간판의 T2 고신호다발성병변이첫영상에비해호전된것을확인하였다. 스테로이드를투약후발열없이안정적인상태였으며, 입원 51일째퇴원하였고특별한증상없이류마티스내과외래에서통원가료중이다. 고찰베체트병의심장침범은유병률이명확하게보고되지않았으나여러연구들에서전체베체트병환자들중대략 7-46% 의침범이보고되며, 다른기관침범에비해사망률및이환률이높아진단이매우중요하다 [1]. 심장을침범한베체트병은드물고전형적인베체트병에서나타나는초기증상과는다른비전형적인증상들을주소로나타나는경우도다수있기에, 발열및오한을주소로내원하여감염성심내막염으로진단받고본증례와같이수술및치료경과도중뒤늦게베체트병으로진단받기도한다 [3]. 심장을침범한베체트병은대부분이대동맥근부를포함한대동맥염의형태로나타나며대동맥판막파괴및대동맥판막부전으로이어진다 [4]. 베체트병심장침범에서특징적인심초음파소견을보이는데이와관련된몇몇의연구들을살펴보면모두공통적으로대동맥판막이상당히얇아지며과잉성이보이고, 판막륜 (annulus) 내무에코공간이특징적으로나타남을보고하였다 [5]. 우리증례에서도수술전심초음파를재검토한결과이와같은특징을찾아볼수있었다. 그러나심초음파만으로베체트병심장침범과감염성심내막염이잘구분이되지않는경우도있다. 베체트병심장침범에서종종유동적인종괴를동반하는데이것은증식증과잘구분이되지않으며, 무에코공간은감염성심내막염에서동반된농양이진행하여그범위가넓어진양상과비슷하여감염성심내막염으로오인되기도한다 [5]. Lee 등 [6] 은베체트병심장침범환자들의심장수술후병리조직검사를바탕으로베체트병에서특징적인병리조직소견을발표하였는데대동맥기부 (aortic root) 에급성, 만성의다양한염증소견이혼재한대동맥판막염및미소농양이관찰되고, 광범위하게내피조직이상실되며그자리를섬유소의침착물로대체된소견 (red-painting sign) 을보인다고보고 하였다. 이러한소견은빈도는낮으나감염성심내막염에서도나타날수있는것으로보고되었다. 그러나감염성심내막염은베체트병의심장침범이주로대동맥판막이나삼첨판을침범하는것에비해어떠한판막이라도침범할수가있고, 급성혹은아급성의단일한단계의염증소견을보인다. 또한조직을그람및특수염색으로염색시미생물이조직에서보이며조직및혈액배양에서배양되는균이있고구강, 성기궤양이나타나지않는다는점이차이점으로나타난다. 우리증례에서수술후병리조직검사결과를다시분석했을때이와같은베체트병에서특징적으로나타날수있는병리소견이관찰되었다. 즉, 그람및특수염색에서확인된미생물이없었으며혈액, 조직에서배양된균이없었고, 심장초음파와병리소견에서베체트병에서특징적인소견을종합적으로판단하여배양음성심내막염보다베체트병의심장침범가능성이높은것으로판단후스테로이드를사용하였고임상증상및염증수치의호전을확인하였다. 베체트병의발병은명확하지않으나다양한기관을침범하고임상증상의악화와호전을반복하는데근골격계를침범하는경우, 가장흔하게보고된증상은관절염및관절통이었고드물게골괴사, 근육통, 섬유근육통이보고되었다 [7]. 그러나뼈를직접침범하여척추골수염양상으로발생한베체트병의증례보고는없었다. 척추골수염진단을위해서조영증상자기공명영상이많이이용되는데전형적으로감염발생후약 1-2일내염증성부종으로인해정상골수신호의변화를보이게되고, T1 강조영상에서골수의신호가떨어지며 T2 강조영상에서는골수신호가증가되는소견을보인다. 자기공명영상은약 90% 의정확도로척추골수염을진단가능하고높은음성예측도를보이나, 양성예측도는반응성골수부종등비감염성원인으로인한신호변화도골수염과같은변화를보일수있기에높은편은아니다. 척추골수염이진행할수록종판 (endplate) 및추간판, 주변연조직으로범위가넓어지며결국에는종판이파괴되며척추인접농양등으로퍼지게되는것이특징적인소견이다 [8,9]. 그러나우리증례에서자기공명영상을확인시골수의염증시나타나는신호변화는나타나나골수침범에비해종판침범은명확하지않고주변조직으로파급도심하지않아전형적인척추골수염소견을보이지는않았으나, 골수를침범하는진행성염증으로보이는신호변화가관찰되었고침을맞은과거력, 발열등임상증상고려시척추골수염을가장먼저생각하였다. 우리증례에서는항생제사용전뼈조직검사를시행하였고검체및혈액에서배양된균이없고, 그람, AFB,

5 - 윤희영외 6 인. 심장침범베체트병 - PAS 염색에서도모두음성으로확인되었으며조직검사에호중구및육아종소견은없었다. 이와같은결과를고려할때척추병변역시베체트병침범가능성을고려해볼수있으며스테로이드투약후 17일추적검사한자기공명영상에서병변은호전이확인된점은척추골수염이발생한베체트병을시사하는소견이다. 일반적인혈액배양에서균이배양되지않는배양음성심내막염은진단기준의차이, 역학적요인, 혈액배양전항생제사용의유무등여러가지요인에의해차이는있으나총심내막염증례중약 % 를차지하는것으로알려져있다. 외국의자료이기는하지만이러한배양음성심내막염은전체심내막염에서많게는 30% 정도로보고하고있고, 가장흔한원인으로 Q열과 Bartonella로보고하고있다 [10]. 우리증례에서는모든배양검사에서음성으로확인되었으며두차례시행한 Q열, Bartonella 항체검사역시음성으로확인되었고여러항생제사용에도임상증상의호전이없었으나스테로이드사용후임상증상의호전이확인되어감염성심내막염보다는베체트병의심장침범에합당한것으로판단하였다. 그러나실제로이환자는베체트씨병의진단기준으로많이사용하는 Internation Study Group (ISG) 에서반복되는구강궤양만을만족하고다른기준은충족하지않았다. 이전에이등도 12명의심장을침범한베체트병을분석한논문에서도 2명을제외하고모두입원당시에 ISG 기준을만족하지않는것으로보고하였다 [6]. 그러므로베체트병은다양한임상상으로나타날수있기때문에일반적으로널리쓰이고있는진단기준에부합하지않는경우가있으므로주의가필요하다. 따라서우리나라와같이베체트병의유병률이높은지역에서는배양음성심내막염이의심되는경우베체트병의심장침범의가능성도원인이될수있으므로여기에감별진단이필요하다고생각한다. 요약 었으나치료과정에서비전형적인임상경과를보여병리조직검사및영상자료를재검토하여베체트병으로진단된증례를문헌고찰과함께보고한다. 중심단어 : 베체트병 ; 배양음성심내막염 ; 척추골수염 REFERENCES 1. Sezen Y, Buyukhatipoglu H, Kucukdurmaz Z, Geyik R. Cardiovascular involvement in Behçet's disease. Clin Rheumatol 2010;29: Park KM, Song JK, Kang DH, et al. Clinical characteristics of patients with cardiac involvement in Behçet's disease. Korean Circ J 2005;35: Zou Y, Ni Y, Liu X, Chen X. Misdiagnosis of Behçet's disease with unknown protracted fever and chill after surgical excision of cardiac tumor. Rheumatol Int 2012;32: Grimaldi A, De Gennaro L, Chiara Vermi A, et al. Cardiac valve involvement in systemic diseases: a review. Clin Cardiol 2013;36: Poppas A, Coady M. Echocardiographic findings and cardiac surgical implications of aortitis and valvulitis in Behçet's disease. J Am Soc Echocardiogr 2009;22: Lee I, Park S, Hwang I, et al. Cardiac Behçet disease presenting as aortic valvulitis/aortitis or right heart inflammatory mass: a clinicopathologic study of 12 cases. Am J Surg Pathol 2008;32: Bicer A. Musculoskeletal Findings in Behcet's Disease. Patholog Res Int 2012;2012: Palestro CJ, Love C, Miller TT. Infection and musculoskeletal conditions: Imaging of musculoskeletal infections. Best Pract Res Clin Rheumatol 2006;20: Zimmerli W. Clinical practice. Vertebral osteomyelitis. N Engl J Med 2010;362: Fournier PE, Thuny F, Richet H, et al. Comprehensive diagnostic strategy for blood culture-negative endocarditis: a prospective study of 819 new cases. Clin Infect Dis 2010; 51: 저자들은척추골수염과배양음성심내막염으로진단되

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ºÎÁ¤¸ÆV10N³»Áö case of brugada syndrome presented as chest pain STRCT rugada syndrome was described in 1992 as a new clinical entity characterized by electrocardiographic STsegment elevation in the right precordial leads