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간조직 검사에서 호산구성 혈관염 증명으로 진단된 churg-strauss 증후군 1예김형상1, 정형기1, 김동현1, 유지은1, 김 영2, 고영일1
전남대학교 의과대학 1알레르기내과학교실, 2병리학교실
A case of churg-strauss syndrome: evidence of eosinophilic vasculitis on liver biopsyHyoung Sang Kim1, Hyung Ki Jeong1, Dong-Hyun Kim1, Jieun Yu1, Young Kim2, Young-Il Koh1
Departments�of�1Allergy,�Asthma�and�Clinical�Immunology�and�2Pathology,�Chonnam�National�University�Medical�School,�Gwangju,�Korea
Purpose:�Churg-Strauss�syndrome�(CSS)�is�a�rare�disease�characterized�by�pulmonary�and�systemic�small�vessel�necrotizing�vasculitis�and�peripheral�blood�eosinophilia�occurring�in�asthmatics.�Cases�of�CSS�with�hepatic�involvement�have�been�rarely�reported.�Here,�we�reported�a�case�of�CSS�involving�liver,�in�which�liver�biopsy�revealed�eosinophilic�vasculitis.Methods:�A�75-year-old�man�complained�of�dyspnea�and�hemoptysis.�He�had�severe�blood�eosinophilia�(white�blood�cell�28,320/μL,�eosinophils�79%).�Computed�tomography�of�chest�and�abdomen�showed�infiltrations�in�lungs�and�multifocal�infiltrations�in�both�hepatic�lobes.�Methacholine�PC20�was�2.89�mg/mL,�which�was�in�asthmatic�range.Results:�Ultrasonography-guided�liver�biopsy�was�performed,�showing�eosinophilic�vasculitis�and�portal�granulomas.�CSS�can�be�diagnosed�based�on�evidence�of�asthma,�blood�eosinophilia,�pulmonary�infiltration�and�vasculitis�on�biopsy.Conclusion:�Taken�together,�in�a�suspected�case�of�CSS�presenting�as�hepatic�involvement,�liver�biopsy�may�be�useful�to�demonstrate�the�presence�of�vasculitis.�(����������������������������������������������������������������������������������
Keywords:�Churg-Strauss�syndrome,�Liver,�Biopsy,�Vasculitis
서 론
Churg-Strauss증후군(Churg-Strausssyndrome,CSS)은연간발생률이인구백만명당1–3예정도로매우희귀한질환이다.1)CSS환자의95%이상에서천식이동반되어있으며,치료하지않았
을경우에는5년생존율이25%정도로예후가매우좋지않다.2)
CSS는1951년Churg과Strauss의보고3)에의해처음으로정의되었으며,괴사성혈관염,조직과주위혈관에호산구침윤,혈관외의육아종이있을때로정의하였다.1984년Hammersmith병원의Lanham등4)은천식과1,500/μL이상의말초혈액호산구증가소견을보일때,폐이외의기관에서두개이상의전신적혈관염소견
이있다면CSS로진단이가능하다고하였다.1990년American
CollegeofRheumatology(ACR)에서는천식,10%이상의혈액호산구증가,신경병증,이동성폐침윤,부비동이상소견,혈관주위
의호산구침윤등의기준으로CSS를정의하였으며,6가지항목중에서4가지이상을만족하면민감도85%,특이도99.7%로CSS를진단할수있다고하였다.5)
CSS는전신소혈관의혈관염에의해내부장기가대부분침범될수있는질환으로,드물게간이침범되는증례도보고되어있다.6-9)그러나간조직검사의병리학적소견을통해CSS를진단하여보고
한증례는거의없다.6)저자들이문헌을고찰한결과국내에는간조
직검사로CSS를진단한증례보고는아직없었다.저자들은CSS가의심되는환자에서간조직검사를통하여CSS를확진하였기에이를보고하고자한다.
Allergy�Asthma�Respir�Dis�1(2):164-167,�June�2013� http://dx.doi.org/10.4168/aard.2013.1.2.164
pISSN:�2288-0402eISSN:�2288-0410
CASE REPORT
Correspondence to: Young-Il KohDepartment of Allergy, Asthma and Clinical Immunology, Chonnam National University Hospital, Chonnam National University Medical School, 42 Jebong-ro, Dong-gu, Gwangju 501-757, KoreaTel: +82-62-220-6580, Fax: +82-62-225-8578, E-mail: [email protected]: November 27, 2012 Revised: January 28, 2013 Accepted: January 28, 2013
© 2013 The Korean Academy of Pediatric Allergy and Respiratory DiseaseThe Korean Academy of Asthma, Allergy and Clinical Immunology
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/3.0/).
김형상 외 • 간조직의 호산구성 혈관염이 증명된 CSS 증후군 1예 Allergy�Asthma�Respir�Dis
http://dx.doi.org/10.4168/aard.2013.1.2.164���165
증 례
환자:박OO,75세남자
주소:호흡곤란과객혈
현병력:내원2주전부터호흡곤란과객혈이발생하여타병원에내원하였고,당시시행한혈액검사에서호산구증가(백혈구28,320/μL,호산구79%[22,370/μL])와단순흉부방사선사진에서다발성폐침윤소견이관찰되어본원으로전원되었다.
과거력:5년전진단받은당뇨와고혈압으로타병원에서약물복용중(aspirin100mg,telmisaltan/amlodipine80/5mg,glimepiri-de2mg)이었으며,최근약물종류의변화는없었다.천식,비염,아토피피부염기왕력은없었다.가끔소고기를날로섭취한적이있었다.
가족력:알레르기질환에대한가족력은없었다.활력 징후:혈압160/100mmHg,맥박수82회/min,호흡수20
회/min,체온36.0°C이었다.신체 검사:타병원에서보내온소견서에는천명음이들린다고
하였으나,본원내원당시천명음은청진되지않았고,우측두번째늑간에서수축기잡음이청진되었다.말초부종이나피부발진등은없었고신경학적이상소견도관찰되지않았다.
검사실 소견:혈액검사에서백혈구는27,200/μL(호산구75.4%[20,500/μL])로호산구증가를보이고,혈색소10.6g/dL,혈소판404,000/μL를보였으며,간기능검사에서aspartateaminotrans-ferase22U/L,alanineaminotransferase24U/L,직접빌리루빈0.73mg/dL으로정상이었고,신기능검사에서bloodureanitrogen13.8mg/dL,creatinine1.1mg/dL,요검사에서는단백뇨2+(100mg/dL)를보였다.동맥혈가스분석에서pH7.4,PO2120mmHg,PCO234.8mmHg,HCO321.8mmol/L이었다.혈청총immuno-
globulin(Ig)E는4,140IU/mL으로증가되어있었다.항핵항체(an-tinuclearantibody)와항중성구세포질항체(antineutrophilcyto-plasmicantibody)는음성을보였고,erythrocytesedimentationrate은44mm/hr으로증가되어있었다.말초혈액도말검사에서경도빈혈과함께심한호산구증가증이
관찰되었다.셀로판후층도말표본에서기생충란에대한검사는음성이었고,혈청에서시행된기생충-특이IgGenzyme-linkedim-munosorbentassay(ELISA)검사에서간흡충,폐흡충,낭미충,스파르가눔에대해서모두음성이었으나(Sunrise,TecanGroupLtd.,Männedorf,Switzerland),개회충에대한항체검사는(EVOLIS,Bio-RadLaboratoriesInc.,Hercules,CA,USA)양성이었다.트립신
분해효소(tryptase)는9.31μg/L으로정상이었고(ImmunoCAP,PHARMACIA,Sweden),호산구양이온단백(eosinophiliccationicprotein)은200μg/L으로증가되어있었다(ImmunoCap,PhadiaAB,Uppsala,Sweden).Troponin-I은0.07ng/mL으로정상이었고,VitB12은>1,476pmol/L(정상범위,156–672pmol/L)로증가되었
으며,humanimmunodeficiencyvirus검사는음성이었다.폐기능 및 기도과민성 검사:Forcedexpiratoryvolumein1sec-
ond(FEV1)1.92L(예측치61.3%)FEV1/forcedexpiratoryvolume73%이었고,기관지확장제반응검사에서는150mL(8.9%)증가되
어천식의기준을만족하지못했지만,7일후시행된메타콜린기관
지유발검사에서PC20가2.89mg/mL으로기도과민성의존재가증명되어천식으로진단되었다.
방사선 소견:단순흉부방사선검사에서양측폐야에음영이증가되었고,흉부전산화단층촬영에서다수의다발성폐침윤(Fig.1A)과심낭에삼출액소견(Fig.1B)이관찰되었다.복부전산화단층촬영에서는양쪽간엽에호산구침윤으로의심되는다수의결절
이관찰되었다(Fig.2).부비동컴퓨터단층촬영에서는부비동염소
A B
Fig. 1. Chest computed tomography shows multiple small nodules with surrounding ground grass opacities (A) and pericardial effusion (B).
Kim�HS,�et�al. • A case of CSS: eosinophilic vasculitis on liver biopsyAllergy�Asthma�Respir�Dis
166���http://dx.doi.org/10.4168/aard.2013.1.2.164
견은관찰되지않았다.심초음파 소견:심초음파에서우심실전방으로0.4cm,좌심실
후방으로0.35cm의심낭삼출액이관찰되었고,이외에도좌심실
비대,경증의대동맥협착,삼첨판역류,폐동맥고혈압등의소견이관찰되었다.
간조직 검사:천식과호산구증가증으로CSS를의심하고간침
윤이있는부위에대해서초음파유도하에조직검사를시행하였
다.조직검사에서전반적인호산구침윤(Fig.3A),호산구성혈관염
(Fig.3B),문맥의호산구침윤및육아종형성등의소견이관찰되
었다.임상 경과:개회충특이IgGELISA에서양성소견을보여alben-
dazol1일800mg을4일동안경험적으로투여하였으며,CSS로진단된이후에는심낭염등의불량예후인자의존재가관찰되어,
methylprednisolone1일62.5mg을8일동안정맥주사하였고,이후에는1일prednisolone60mg을경구투여하고,동시에경구cy-clophosphamide1일50mg을13일간투여하였다.입원15일째혈액검사에서백혈구8,800/μL(호산구6.2%[545/μL])으로호산구수가감소되고,특별한이상증상을호소하지않아퇴원하였다.이후외래에서7주동안은prednisolone을점차적으로감량하면서cyclophosphamide를1일100mg으로증량하여투여하였으며,이후에는cyclophosphamide는중단하고prednisolone만을점차감량하여,현재격일로20mg을투여하면서재발없이경과관찰중이다.방사선검사를시행하여폐와간의침윤병변의호전을확인
하고자하였으나환자의경제적인이유로시행하지못하였다.천식
에대해서는고용량흡입스테로이드,지속베타2항진제,류코트리
엔수용체길항제로조절하였고,FEV1은2.57L(예측치88%)로증가되었다.
고 찰
본증례는ACR에서정한CSS의6가지기준중에서천식의존재,10%이상혈액호산구의증가,폐침윤,간조직의호산구성혈관염등의4가지소견이증명되어진단할수있었다.CSS는일반적으로3단계의임상경과를거친다.첫번째는비염,부비동염,천식등이나타나는단계이고,두번째는혈액내의호산구증가와호산구의조직침윤이발생하는단계이며,세번째는혈관염이발생하는단계이다.4)그러나모든CSS환자가이러한단계를거쳐서나타나는것은아니고,천식증상없이초기에혈관염이바로발생하는경우
도있으며,이러한경우는진단이늦어질수있어예후가좋지않는것으로알려져있다.10)증례의환자는내원전천식을진단받거나또는증상을경험한적은없었다.본원내원전타병원에서청진상
A B
Fig. 3. Liver biopsy shows diffuse eosinophilic infiltration (A) and eosinophilic vasculitis (B, arrows) (H&E, × 200).
Fig. 2. Abdomen computed tomography shows multiple low attenuated lesions at both hepatic lobes.
김형상 외 • 간조직의 호산구성 혈관염이 증명된 CSS 증후군 1예 Allergy�Asthma�Respir�Dis
http://dx.doi.org/10.4168/aard.2013.1.2.164���167
천명음이청진되었고,폐기능이감소되어있었으며,메타콜린기관
지유발검사에양성을보여천식이동반되어있음을진단할수있었다.하지만부비동컴퓨터단층촬영확인결과비염또는부비동
염은동반되지않았음을알수있었다.따라서본증례는CSS의3단계중첫번째단계에해당되는증상이잘나타나지않은상태로,두번째및세번째단계가바로발생한경우로생각할수있다.본증례에서는CSS의간침범이확인되었다.CSS에서간침범은
흔하지는않지만보고된바가있다.Harada등6)은발열과간기능이상으로내원한증례에서간조직검사를통해CSS로진단하였다.Sironen등7)은충수염과담낭염증상으로내원한CSS증례에서간표면에미세결절(micronodular)이발생한것을보고하였고,Yuk-sel등8)은간기능수치가증가된CSS에서간조직검사를통해활동
성간염소견을관찰한증례를보고하였다.Otani등9)은CSS의혈관염에의해서간병변으로가는소혈관의협착이발생하여간경색
(liverinfaction)이발생한경우를보고하였다.CSS의조직학적소견으로는호산구침윤과괴사가있고,소혈관및혈관주위에호산
구혈관염,거대세포성혈관염,괴사성육아종등을들수있다.11)증례에서는복부전산화단층촬영에서CSS의간침범이의심되어조직검사를시행하였고,간조직에서호산구침윤및호산구혈관
염,문맥의호산구침윤및육아종형성등을확인할수있었다.Sirogen등7),Yuksel등8),Otani등9)은간조직에서호산구침윤또는혈관염등의소견을직접확인하지못하였고,Harada등6)은간조직에서간동맥의유섬유소변성괴사(fibrinoidnecrosis)와함께간문맥주위의호산구침윤을확인하여본증례와비슷하게CSS를진단하였다.CSS는주로폐,신장,심장,피부,신경등을침범하
기때문에,12)조직학적소견을증명하기위해서는폐,위장관,피부,말초신경부위의조직검사등이주로이용된다.증례처럼CSS가의심되는경우에간침범의소견이있고다른부위의조직검사가어렵다면,초음파유도하에간조직검사를시행하여특징적인조직
학적소견을증명함으로써CSS를진단할수있을것이다.본증례는심초음파에서심낭삼출액이보이고있어,심낭염이동
반되어있는CSS환자로생각된다.CSS환자의약50%에서심장을침범하고,심장을침범시불량한예후를갖는것으로알려져있다.13)증례의환자는천식,비염,부비동염의기왕력이없이바로간이침범되면서발생한CSS로,비교적발병초기로생각되며동시에심장도침범된경우라할수있다.내원당시요검사에서단백뇨가발견되어CSS의신장침범을의심해볼수있다.그러나5년전부터
당뇨병을가지고있어이에의한단백뇨일가능성도배제할수없다.이상에서보듯이CSS는간침범을동반할수있으며,CSS가의
심되는임상적상황에서간침범이있고다른장기의조직검사가가능하지않은경우에간조직검사를통하여특징적병리소견을증명하여CSS를쉽게진단할수있을것이다.
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