The Korean Journal of Nephrology 2010;29:115~119 Case Report 1) 타카야수동맥염의진단과치료과정에서 Positron-Emission Tomography 의역할 한양대학교의과대학내과학교실 1, 영상의학교실 2, 핵의학교실 3

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1 Case Report ) 타카야수동맥염의진단과치료과정에서 Positron-Emission Tomography 의역할 한양대학교의과대학내과학교실, 영상의학교실 2, 핵의학교실 3 박세우 ㆍ이창화ㆍ김근호ㆍ정명호ㆍ박수역ㆍ송순영ㆍ최윤영ㆍ강종명 2 3 The Role of Positron-Emission Tomography in Diagnosis and Assessment of Treatment Response in Takayasu Arteritis Se Woo Park, M.D., Chang Hwa Lee, M.D., Gheun-Ho Kim, M.D. Myung Ho Jeong, M.D., Soo Yuck Park, M.D., Soon Yeong Song, M.D. 2 Yun-Young Choi, M.D. 3 and Chong Myung Kang, M.D. Departments of Internal Medicine, Radiology 2 and Nuclear Medicine 3 Hanyang University College of Medicine Takayasu arteritis is a nonspecific granulomatous inflammatory arteriopathy of unknown cause that results in occlusive obliteration and less commonly aneurysmal degeneration of large and medium-sized elastic arteries. The diagnosis of Takayasu arteritis and the assessment of its progression and extent remain challenging, especially in patients presenting with a constellation of non-specific symptoms and laboratory tests. The standard diagnostic procedures include biopsy, arteriography, sonography, and magnetic resonance angiography. However, these procedures are invasive or largely operator-dependent, and document only morphological changes such as stenosis, occlusion and aneurysmal transformation which mainly occur in late stages of the disease. On the other hand, Positron-emission tomography is an operator-independent, non-invasive metabolic imaging modality which plays a major role in diagnosis of nonspecific inflammatory diseases. We report a case in which Positron-emission tomography was applied to the detection of Takayasu arteritis and assessment of its disease progression. Key Words : Takayasu arteritis, Positron-Emission Tomography, Disease progression, Diagnosis 타카야수동맥염은 서 론 908년일본의안과의사인타카야수에 의해처음으로발견된질환으로주로대동맥궁에서분지하는혈 관들의완전또는불완전폐쇄로인해말초부위에맥박소실과 혈액순환장애를초래할수있다 ). 주로일본과한국을비롯한 극동아시아에서대부분의환자가발생하고서구에서는발생빈도 가낮다고알려졌다 2). 접수 : 2009년 0월 5 일, 승인 : 2009년 월 6일책임저자 : 강종명서울시성동구행당동산 7번지한양대학교의과대학신장내과전화 : 02) , Fax : 02) kangjm@hanyang.ac.kr 일반적으로타카야수동맥염은 ACR 진단기준 (Table ) 에따라임상증상과혈관조영술로진단이가능하지만, 이것은 질병이급성기를지나만성적인폐쇄성병변을동반해야기준을 만족할수있다는한계가있다. 급성기에는고열, 야간발한등 비특이적인전신증상만호소하는경우가많으며, 이후혈관협 착이서서히진행되면서침범혈관에따라특징적인증상들을 나타낸다 3). 따라서 ACR 진단기준은이미국소적인혹은전신 적인혈관협착을동반하는경우를기반으로제창된것이기때 문에질병초기미세한염증반응에의한비특이적인증상변화 를간과하기쉽다 2). 혈관조영술은타카야수동맥염의확진에도움되지만질병활 성도를측정하고추적관찰하는데침습적이라는단점이있고, 혈 청학검사로서급성기염증지표자 (acute phase reactants)

2 역시질병의활성도를정확히반영하지못하여약 50% 의환자 에서는임상양상과일치하지않는다고한다 4). 최근 Positron- Emission Tomography 의영역이확대됨에따라서악성신 생물의진단, 치료및추적관찰에서뿐아니라비특이적염증성 질환에서의역할이커졌다. 이를토대로현재많은연구들이이 루어지고있으나국내에서는타카야수동맥염의진단, 치료및 경과에서 Positron-Emission Tomography의역할을적용 한증례가아직없었기에문헌고찰과함께보고하는바이다. 증 환자 : 신, 남자, 6세 주 소 : 두통 현병력 : 환자는 례 0여일전갑자기발생한두통으로개인병원 을방문한결과수축기혈압이 200 mmhg 이상상승하여본 원신장내과로의뢰되었다. 두통은뒤통수에심하였고지속적이 었으며, 짓누르는듯한양상이면서진통제복용에효과가없었 다. 과거력 : 7년전좌측요로협착으로수술받았으나원인질환 과수술명은환자가잘알지못하였다. 결핵의기왕력은없었다. 가족력 : 특이사항없음. 사회력 : 환자는중학교 없었다. 2 학년이었고, 음주나흡연의경험은 진찰소견 : 내원당시활력징후는우상지혈압 20/20 mmhg, 좌상지혈압 60/90 mmhg, 맥박 90 회/ 분, 호흡수 20 회/ 분, 체온 36.8 였다. 환자의의식은명료하였고, 두경부 에서경동맥잡음이들리지않았으며비정상적인림프절은촉지 되지않았다. 심음과호흡음은정상이었고, 복부에서경직소견 이나압통및반발통은관찰되지않았으며, 늑척추각압통은없 었다. 우완보다좌완의맥박이약하였으나양쪽대퇴동맥의맥박 은잘촉지되었다. 안저검사에서혈관이상등특이소견은보이 지않았다. 검사소견 : 일반혈액검사에서백혈구 9,800/mm 3, 혈색소 4. g/dl, 적혈구용적 43.7%, 혈소판 29,000/mm 3 였다. 혈액검사에서 BUN 6 mg/dl, creatinine 0.9 mg/dl, ESR 9 mm/hr, CRP 0.3 mg/dl 이었으며, 요검사의이상소견은 acid, metanephrine, norepinephrine, epinephrine은 모두정상이었다. 내원당시혈장레닌활성도는 8.4 ng/ml/hr 로상승되었고, 혈중갑상선호르몬, aldosterone 및 cortisol 농도는정상범위였다. 방사선소견 : 흉부단순촬영에서심비대는없었고, 심초음파 에서좌심실구혈률은 66% 였다. 복부전산화단층혈관조영술결 과, 상복부대동맥에서우신동맥기시부까지동맥벽의비후와전 반적인협착이있었고 (Fig. A), 특히우신동맥근위부약 2 cm 에걸쳐서심한동맥벽의비후와협착이관찰되었다 B, C). (Fig. 진단및치료경과 : 신동맥협착의의의를알아보고자시행한 Positron-Emission Tomography 에서상행및하행흉부 대동맥, 복부대동맥과우측신동맥부위에서 Standard Uptake Value (SUV, FDG accumulation) 가증가하였고특히대동 맥궁에서.9 로가장높은수치를보였다 (Fig. 2A). 이어서 시행한대동맥조영술에서흉부와복부대동맥의전반적인협착, 좌쇄골하동맥의 50% 협착과우신동맥근위부의심한협착 (94%) 을관찰하여 (Fig. 3A) 우측신동맥의풍선혈관성형술 과스텐트삽입술을시행하였다 (Fig. 3B). 시술후혈압은 20/80 mmhg 으로정상화되었고두통도호전되었다. 따라서 퇴원할때는항고혈압제투약없이 aspirin 00 mg qd와 없었다. 24시간요를모아측정한 free cortisol, vanilmandelic pre- dnisolone 0 mg qd 처방하였으며, 이후 prednisolone은 2 Fig.. Abdominal CT angiography. An ectatic change of aorta from lower thoracic level to upper abdominal level was found in the sagittal section (A). Focal severe stenosis and wall thickening of right renal artery were documented in reconstruction images (B, C).

3 Se Woo Park, et al. : The Role of Positron-Emission Tomography in Takayasu Arteritis 개월간복용한후중단하였다. 그러나이때혈압이 50/80 mmhg로다시상승하여 ACE inhibitor 를추가처방하였다. 8개월뒤추적시행한 Positron-Emission Tomography 결과초기 Positron-Emission Tomography에서관찰되었 던대동맥궁의대사활성도증가소견은사라졌다 (Fig. 2B). Fig. 2. Positron-emission tomography. Moderate hypermetabolic activity at aortic arch (SUVmax :.77) was documented at initial positron-emission tomography (A). After treatment of Takayasu arteritis over.5 years, uptake of 8 F-FDG at previous lesion was decreased to normal range (SUVmax:.50) in the follow-up positronemission tomography (B). 고 타카야수동맥염은주로대동맥과대동맥의주분지에발생하 는만성염증성질환으로젊은여성에서호발하며극동을비롯 한동양권에서유병률이높은것으로알려져있다 5). 아직병인 은명확하게밝혀진바없지만감염, 면역학적결함혹은자가면 역등에의할것이라는여러가설들이현재까지설득력을얻고 있다 6). 임상경과는매우다양하여초기급성염증기에는주로 발열, 피로, 식욕저하, 관절통, 근육통등이나타나다가후기무 맥기로진행할수록전신증상이사라지고침범된동맥의협착이 찰 나폐색에따른임상상으로발현한다 6, 7). 본증례의환자는젊은연령임에도불구하고심한고혈압이 있었고좌우상완의수축기혈압이 50 mmhg 정도차이를보 여타카야수동맥염에의한신혈관성고혈압등이차성고혈압 을의심할수있었다. 그러나이러한임상상만으로타카야수동 맥염을진단하기쉽지않아서, 외국의한연구에따르면증상을 처음호소한시점으로부터 3년이내진단된경우는 20% 미만 이라고한다 4). 거대세포동맥염과는달리조직검사가쉽지않으 며적혈구침강속도와 C 반응성단백등급성기염증표지자의 상승역시타카야수동맥염에진단적이지못하다. 그외에도 tissue factor, von Willebrand factor, sicam-, svcam- 및 se-selectin 등이상승할수있으며경미한 빈혈과고글로불린혈증등을보일수있으나비특이적이다 8). 타카야수동맥염은 The American College of Rheu- matology (ACR) 진단기준 (Table ) 6가지중 3가지이상 을만족할때민감도 90.5%, 특이도 97.8% 로진단할수있다 2). 그러나서론에서언급했듯이이기준은폐쇄성병변을동반 하지않은질병초기에는진단기준을만족시키지못할수있으 며, 대동맥조영술을통하여혈관의협착이나폐쇄를증명하는 Fig. 3. Renal arteriography and intervention. Severe stenosis at right proximal renal artery was demonstrated in renal angiography (A). Right renal artery stenosis was successfully treated by balloon angioplasty and stenting (B).

4 Table. ACR Criteria for the Diagnosis of TA Age at disease onset <40 yrs: Development of symptoms or findings related to TA at age <40 yrs Claudication of extremities: Development and worsening of fatigue and discomfort in muscles of one or more extremities while in use, especially the upper extremities Decreased brachial artery pulse: decreased pulsation of one or both brachial arteries abp difference >0 mmhg: Difference >0 mmhg in systolic BP between arms Bruit over subclavian arteries or aorta: Bruit audible on auscultation over one or both subclavian arteries or abdominal aorta Arteriogram abnormality: Arteriographic narrowing or occlusion of the entire aorta, its primary branches or large arteries in the proximal upper or lower extremities, not due to arteriosclerosis, fibromuscular dysplasia or similar causes; changes usually focal or segmental ACR, The American College of Rheumatology; TA, takayasu arteritis, abp, arm blood pressure. Diagnosis of TA can be made when a patient has at least three of these six criteria. The presence of any three or more criteria yields a sensitivity of 90.5% and a specificity of 97.8%. 것은매우침습적이라는한계가있다. 최근들어이러한혈관의협착이나폐쇄를증명하기위한비 침습적이미지도구들이많은발전을이루었다. 자기공명촬영법 및혈관조영술, 전산화단층촬영법및혈관조영술, 고해상도초 음파등이전통적인혈관조영술을대체할수있다는증거는없 지만타카야수동맥염의진단에보조적역할을하고있다 9). 그 러나이러한영상학적검사들역시혈관벽의염증성변화정도 를반영하지못하기때문에새로운검사의필요성이대두되었다. 한후향적연구에서 Positron-Emission Tomography는 염증을동반한 4 mm 이상의혈관벽에서비정상적인 8 F- FDG 섭취증가를보인다는사실에기초하여약 92% 의민감도 와 00% 의특이도로타카야수동맥염을진단하였다고보고하 였다 0). 또다른연구에서는질병초기에폐쇄에의한증상없이 비특이적인증상만으로발현된환자를대상으로 Positron- Emission Tomography 를시행하였을때다른영상학적검 사에비해타카야수동맥염을진단하는데더우월하다고보고하 였으며, 특히조영증강 CT를동시에시행하였을때대동맥과 그분지및폐동맥의침범유무판단에있어서 Positron- Emission Tomography 를단독으로시행하는것보다더민 감도가높았다고하였다 0, ). 본증례에서도조영증강 CT와 Positron-Emission Tomography 를함께시행하여협착의 부위와범위, 대사성활성화정도를동시에판단함으로써타카야 수동맥염을진단하였다. 추적관찰중질병활성도평가에어떤도구가바람직한지는 아직분명하지않다. 특히혈청학적급성기반응물질은 50% 미 만에서질병활성도와일치하며 8, 2) 다른, 보편적인영상학적 검사소견과도항상일치하지는않는다고한다 3). 가장최근에 발표된한연구에서는 8 F-FDG의혈관벽내흡수정도와임 상적, 생물학적혹은자기공명을이용한영상학적질병활성도 측정등모든변수들사이에서불일치를보였으며따라서질병 활성도의측정에서 Positron-Emission Tomography의역 할은미미하다고결론내린바있다 4). 또다른연구에서도추적 관찰중질병활성도와 8 F-FDG 섭취율간의상관관계가반 드시일치하지는않아서치료후 8 F-FDG 섭취율이감소한 결과가임상적호전에의한것인지혹은동맥벽두께의감소에 의한것인지감별이되지않는한계를가진다고하였다 ). 그러 나다른한편으로, 활성기환자에서적절한치료를통해병변부 위의증가되었던 8 F-FDG 섭취가소실되거나감소되고, 비활 성화기의타카야수동맥염환자나정상인에서는 8 F-FDG 섭 취증가소견이관찰되지않았다는것은 8 F-FDG의동맥벽 내축적이침범된혈관의염증반응과상관관계가있으므로질병 활성도측정에있어서 역할이긍정적이라는근거가될수있다 Positron-Emission Tomography의 5, 6) 따라서. 치료후 Positron-Emission Tomography 와함께임상증상, 혈청 학적급성기반응물질, 영상학적인도구들을서로비교, 상호보 완해야정확한치료효과판정을내릴수있을것이다. 본증례에서도협착이이미심하게진행되었고 C 반응성단 백이 0.3 mg/dl으로정상범위이내였으나 8 F-FDG PET scan와조영증강 CT를이용하여타카야수동맥염을진단하고 질병의범위와활성도를측정하였으며, 이후추적검사로 Positron-Emission Tomography 를이용하여병변부위의활성 도 ( 8 F-FDG 의섭취율 ) 가감소하였음을확인하였다. 아직국

5 Se Woo Park, et al. : The Role of Positron-Emission Tomography in Takayasu Arteritis 내에서 Positron-Emission Tomography를이용하여타카 야수동맥염을진단하고치료의추적관찰을서술한보고는없 었다. 타카야수동맥염의약물요법에서가장중요한것은스테로이 드로서활성기가적응증에해당한다 7). 활성기란 ) 열, 근육통 등전신적증상, 2) 적혈구침강속도의상승, 3) 파행, 맥박소실 등혈관폐쇄에의한증상, 4) 타카야수동맥염에합당한동맥조 영술소견중두가지이상을만족할경우이다 4, 7). Predniso- lone 용량은초기에 0.5- mg/kg/day 또는 mg/ day로시작하여 4주내지 2 주간사용한후, 증상이호전되면 매주또는격주간격으로감량해서하루에 의용량으로수개월간유지한다 7). 요컨대 0 mg 내지 20 mg Positron-Emission Tomography 와조영증강 CT 를통하여타카야수동맥염의질병초기혹은증상이뚜렷하지 않은환자에서진단율을높이고해부학적인오류를줄일수있 다. Positron-Emission Tomography의기능적인영상은 질병의범위와활성도를측정하고, 치료의판정과재발유무를 확인하는데유용할것이라고생각된다. 다만, 아직대규모의전 향적인연구가이루어지지않아타카야수동맥염의진단과치료 및예후판정에서 Positron-Emission Tomography의역 할에대해보다체계적인연구가필요하다. 참고문헌 ) Isselbacher EM, Eagle KA, Desanctis RW: Chapter 45. Diseases of the aorta. in Heart diseases: A textbook of cardiovascular medicine (5th ed), edited by Braunwald E, Philadelphia, WB Saunders Co., 997, p ) Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lie JT, Lightfoot RW Jr: The american college of rheumatology 990 criteria for the classification of Takayasu arteritis. Arthritis Rheum 33:29-34, 990 3) Starchan RW, Wigzell FW, Anderson JR: Locomotor manifestation and serum studies in Takayasu s arte- riopathy. Am J Med 40: , 966 4) Kerr GS, Hallahan CW, Giordano J, Leavitt RY, Fauci AS, Rottem M, Hoffman GS: Takayasu arteritis. Ann Intern Med 20:99-929, 994 5) Koide K: Takayasu arteritis in Japan. Heart Vessels Suppl 7:48-54, 992 6) Johnston SL, Lock RJ, Gompels MM: Takayasu arteritis: a review. J Clin Pathol 55:48-486, ) Mwipatayi BP, Jeffery PC, Beningfield SJ, Matley PJ, Naidoo NG, Kalla AA, Kahn D: Takayasu arteritis: clinical features and management: report of 272 cases. ANZ J Surg 75:0-7, ) Hoffman GS, Ahmed AE: Surrogate markers of disease activity in patients with Takayasu arteritis. A preliminary report from the International Network for the Study of the Systemic Vasculitides (INSSYS). Int J Cardiol 66(Suppl ):S9-S94, 998 9) Andrews J, Mason JC: Takayasu s arteritis - recent advances in imaging offer promise. Rheumatology (Oxford) 46:6-5, ) Webb M, Chambers A, AL-Nahhas A, Mason JC, Maudlin L, Rahman L, Frank J: The role of 8F-FDG PET in characterising disease activity in Takayasu arteritis. Eur J Nucl Med Mol Imaging 3: , 2004 ) Andrews J, Al-Nahhas A, Pennell DJ, Hossain MS, Davies KA, Haskard DO, Mason JC: Non-invasive imaging in the diagnosis and management of Takayasu s Arteritis. Ann Rheum Dis 63: , ) Maksimowicz-McKinnon K, Clark TM, Hoffman GS: Limitations of therapy and a guarded prognosis in an american cohort of Takayasu arteritis patients. Arthritis Rheum 56: , ) Tso E, Flamm SD, White RD, Schvartzman PR, Mascha E, Hoffman GS: Takayasu arteritis: utility and limitations of magnetic resonance imaging in diagnosis and treatment. Arthritis Rheum 46: , ) Arnaud L, Haroche J, Malek Z, Archambaud F, Gambotti L, Grimon G, Kas A, Costedoat-Chalumeau N, Cacoub P, Toledano D, Cluzel P, Piette JC, Amoura Z: Is 8F-fluorodeoxyglucose positron emission tomography scanning a reliable way to assess disease activity in Takayasu arteritis? Arthritis Rheum 60:93-200, ) Kobayashi Y, Ishii K, Oda K, Nariai T, Tanaka Y, Ishiwata K, Numano F: Aortic wall inflammation due to Takayasu arteritis imaged with 8F-FDG PET coregistered with enhanced CT. J Nucl Med 46: , ) Tatsumi M, Cohade C, Nakamoto Y, Wahl RL: Fluorodeoxyglucose uptake in the aortic wall at PET/ CT: possible finding for active atherosclerosis. Radiology 229:83-837, ) Edward DH Jr, Ralph CB, Gary SF, Mark CG, John SS, Shaun R, Clement BS: Giant Cell Arteritis, Polymyalgia Rheumatica, and Takayasu s Arteritis in Kelley s textbook of rheumatology (vol 2), edited by David BH, Gene GH, ed, Elsevier Saunders, Philadelphia, 2008, p

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