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1 대한요로생식기감염학회지 : 제2권제1호 2007년 5월 Korean J UTII Vol.2, No.1, May 2007 원저 성인호산구성방광염의임상특징 : 방광경소견을중심으로 [Abstract] 인제대학교의과대학비뇨기과학교실 전준성 조인래 Clinical Characteristics of Eosinophilic Cystitis in Adults: According to the Cystoscopic Findings Joon Seong Jeon, In Rae Cho From the Department of Urology, College of Medicine, Inje University Gimhae, Korea Purpose: Eosinophilic cystitis is a rare disease, which was reported 15 cases in Korea. We describe our clinical experience with eosinophilic cystitis patients who were confirmed in pathology. Materials and Methods: Six men and two women were diagnosed with eosinophilic cystitis between 2000 and Mean patient age at presentation was 71 years (range 62 to 82). A retrospective chart review was performed to assess clinical presentations, diagnosis, treatment and outcomes. Results: 6 patients (75%) presented with combination of gross hematuria and irritative bladder symptoms. 1 patient had acute urinary retention and 1 patient was asymptomatic. Allergic diseases (asthma, allergic contact dermatitis) were present in 2 patients. The remaining 6 patients were associated with urologic disorders (BPH, bladder carcinoma, bladder stone, etc). Laboratory data include peripheral eosinophilia in 3 of 7 (43%), hematuria in all 8, pyuria in 4 of 8 (50%), positive urine culture 2 of 8 (25%). Cystoscopy showed erythema in all cases and tumor-like lesions or edema in 6 (85%). Transurethral resection of the bladder lesion was performed in 2 cases. All patients received antibiotics, non-steroidal anti-inflammatory drugs (s) and corticosteroids and experienced the marked improvement during a follow-up duration. Conclusion: Eosinophilic cystitis is more common in male than female. Most common presenting symptoms were hematuria and irritating bladder symptoms. Resection of the bladder lesion with systemic treatment of corticosteroids, s and antibiotics showed good results. (Korean J UTII 2007;2:78-82) Key Words: Bladder, Cystitis, Eosinophils 서 론 교신저자 : 조인래, 인제대학교일산백병원비뇨기과경기도고양시일산구대화동 2240 Tel: , Fax: ircho@ilsanpaik.ac.kr 호산구성방광염은 1960년 Brown 1 에의해처음보고된흔하지않은질환으로, 내원당시증상은혈뇨, 방광자극증상, 치골상부동통, 요폐등으로다양하다. 그러므 78

2 전준성 조인래 : 성인호산구성방광염의임상특징 : 방광경소견을중심으로 79 Table 1. Clinical manifestations of 8 patients with eosinophilic cystitis Cases Age Sex Gross hematuria Irritating bladder symptoms Pyuria Associated disease Serum eosinophil (%) 1 64 M M BPH F M TCCa 5 62 F Asthma 5.4 normal 6 66 M prostatic abscess 7 72 M M Bladder stone, BPH 8.8 X-ray finding multiple nodular filling defect on dome of the bladder minimal wall thickening in post wall of the bladder irregular wall thickening on posterior wall and suspicious perivesical fat infiltration diffuse wall thickening without mass filling defect on post, bladder 3.6 normal Cystoscopic findings diffuse erythematous, edematous, polypoid walnut sized mass on posterior wall erythematous, edematous mucosal change on posterior wall and dome erythematous velvety mass on dome erythemaous in the bladder diverticulum erythmaous edematou mass like lesion Tx TURBt+ Antibiotic Steroid+ TURBt+ + Steroid + Steroid multiple erythematous velvety mass on posterior wall Duration of follow up (Mon) BPH: benign prostatic hyperplasia, TCCa: transitional cell carcinoma, TURBt: transurethral resection of bladder tumor, : non-steroidal anti-inflammatory drug 로방광의다른염증성질환과악성종양과의감별이필요하다. 발병원인은명확하지는않으나주로소아와성인여성에서알레르기질환과관련이되어발생하거나, 남성노인에서방광암또는전립선비대증의수술등으로인한방광손상이원인인것으로생각되어지고있다. 2 대한비뇨기과학회지에는약 15례의문헌보고가있으나모두증례형식으로보고되고있어질환의정확한이해가부족하다. 이에저자들은본원비뇨기과에서조직검사를통하여호산구성방광염으로진단되었던 8명의환자들의의무기록을비교분석하여, 호산구성방광염의임상적특징을이해함으로써환자치료에도움을주고자한다. 대상및방법 2000년부터 2006년까지 7년간본원비뇨기과에서시행한방광조직검사에서호산구성방광염으로진단받은 8명을대상으로질환의임상양상, 진단, 치료와치료결과를의무기록을통하여후향적으로조사하였다. 환자들의평균연령은 71세 (62-89) 였고남자가 6명여자가 2명이었다 (Table 1). 결과내원당시육안적혈뇨와방광자극증상을호소한경

3 80 대한요로생식기감염학회지 : 제 2 권제 1 호 2007 년 5 월 Fig. 1. CT of pelvis with intravenous contrast material reveals the irregular wall thickening and protruding mass on the posterior bladder. Fig. 3. Biopsy specimen shows dense infiltration of eosinophils with smooth muscle layers. Fig. 2. Cystoscopy shows the erythematous tumor like mass with mucosal swelling. 우가 6례 (75%) 로가장많았고, 그밖에급성요폐 1례, 무증상으로방광상피암추적방광경검사에서발견된경우가 1례였다. 기저질환및선행요인으로기관지천식, 두발염색제사용으로인한알레르기피부염, 방광이행상피암, 전립선농양이각각 1례였고전립선비대증은 2례였다. 전립선비대증환자 1례는방광결석이동반되었다. 혈액검사가가능하였던 7례가운데 3례 (43%) 에서 5% 이상으로호산구증가가내원당시관찰되었다. 일반뇨검사에서혈뇨는모두에서관찰되었고농뇨는 4례 (50%) 에서관찰되었다. 요배양검사에서균이검출된경우가 2례 (25%) 였고대장균, 그람음성간균이각각검출되었다. 요세포검사에서비정상세포가관찰된예는없었다. 방사선학검사로는요로조영술을 4례에서시행하였으며 2례에서방광내조영제의충만결손이관찰되었고 2 례는정상소견이었다. 복부골반전산화단층촬영은 3례에서시행되었고 2례에서방광벽의비후, 1례에서방광내종물로관찰되었다 (Fig. 1). 모든환자에서방광내시경검사와조직검사가시행되었으며, 내시경소견으로는방광점막의홍반성변화가광범위하게관찰된경우는 5례, 국소적으로관찰된경우가 3례였다. 6례 (85%) 에서벨벳 (velvety) 또는용종의종물로관찰되었고그밖의소견으로는방광점막의부종이관찰되었다 (Fig. 2). 조직병리검사소견으로는방광점막과점막하층에광범위하게호산구침윤이관찰되었으며, 병변절제술을시행한 2례에서는호산구의근층침윤이관찰되었다 (Fig. 3). 외과적치료는내시경하병변절제술이 2례에서시행되었다 (Table 1). 약물치료는전례에서항생제와진통소염제를투여하였고스테로이드는 3례에서투여되었다. 평균추적관찰기간은 5개월 (1-12) 이었고추적검사로는일반뇨검사, 요배양검사, 방광경검사를시행하였다. 추적관찰기간동안증상의재발이나, 추적방광경검사가시행된 4례에서호산구방광염의재발또는진행된경우는없었다.

4 전준성 조인래 : 성인호산구성방광염의임상특징 : 방광경소견을중심으로 81 고찰호산구성방광염은방광에발생하는염증성질환으로방광벽에다수의호산구침윤, 점막의섬유화, 근육의괴사를초래하는질환이다. 2 모든연령에서발생가능하며평균발생연령은 41.6세이다. 성인남녀발생빈도의차이는없으나, 소아에서는남아가여아에비해서약간높은것으로알려져있다. 3 본연구에서는환자의평균나이는 71세였고, 남녀의발생비는 3:1이었다. 국내에서는채등 4 이 1967년 1례를보고한이래약 15례가비뇨기과문헌에보고되었다. 발생기전은 IgE를매개로하는알레르기반응이다. 즉항원이 IgE와결합되면호산구가활성화되고비만세포의탈과립화를촉진함으로써각종 cytokines이분비된다. 5,6 interleukin-5, granulocyte-macrophage colony-stimulating factor는호산구성양이온단백질 (eosinophilic cationic protein) 의분비를자극하는데, 이로인하여세포의염증이초래된다. 7 그러나아직까지질환의직접적인원인은불명확하다. Itano 등 9 은기존논문에발표된 83명의환자들을대상으로호산구성방광염의원인으로추정되는동반질환이나선행요인을분석한결과, 29% 의환자는원인을알수없었고, 환자의 71% 는하나이상의원인과관련이있음을확인하였다. 원인별로는방광이행상피암 25%, 기관지천식과비염 16%, 방광출구폐색 13%, 약제 8.5%, 자가면역질환 8.5%, 기생충감염 2.4%, 호산구성장염 2.4% 등의순서로관련질환이확인되었다. 저자들은환자의 75% 에서원인추정이가능하였는데전립선질환과동반된경우가 3례로가장많았고, 이가운데 1례는전립선비대증과방광결석을같이동반하였다. 알레르기반응이원인이된환자는 2례로혈액검사에서모두호산구의증가가관찰되었다. 방광이행상피암환자의추적방광경검사에서발견된환자는 1례있었으며, 경정맥항암제 (gemcitabine, cisplatin) 를투여받은과거력이있었다. 호산구성방광염의일반적인증상은방광자극증상, 혈뇨, 치골상부동통이다. 급성요폐는어린이와여자들에게서흔하다. 3 그밖에드물지만위장관증상, 피부발적, 기뇨등의증상을동반할수있다. 또한흥미로운사실은표재성방광상피암의 2% 에서방광호산구증을같이동 반한다는것이다. 이는종양의재발과연관이있는데, 방광호산구증이있는종양이없는경우에비해서낮은재발률을보인다. 10 저자들의경우, 육안적혈뇨와방광자극증상을주소로내원한경우가 75% 로가장많았다. 그밖에표재성방광상피암의추적내시경검사에서우연히진단된 1례가있었다. 검사실소견으로는현미경적혈뇨와단백뇨가관찰되고요배양검사는음성인경우가대부분이다. 3 호산구혈증은알레르기과거력이있는환자의약 50% 에서나타날수있으나, 호산구뇨증은호산구가소변에서급격히파괴되므로요검사에서대부분음성으로관찰된다. 9 요로조영술에서는정상으로관찰될수있거나, 방광또는요관에종물로인한조영제의충만결손, 일측또는양측요관확장 9 및수신증 11 이나타날수있다. 초음파와전산화단층촬영에서는방광벽의비후또는방광내종물의형태로관찰될수있으나질환고유의특징적인소견은없다. 3 방광내시경소견은질환의진행정도에따라다양한데병변은벨벳모양, 용종형혹은종괴 (fungating) 형태의종물로관찰되며점막의부종과홍반을같이동반한다. 그러므로질환의진행정도가심할시에는방광종양으로오인될수있다. 8,9 저자들도방광종양과의감별이어려웠던 2례를경험하였고내시경하방광종양절제술후조직검사로확진하였다. 조직학적으로는다수의호산구의점막하층과근육으로의침윤, 점막하부종, 근육의괴사및섬유화가관찰된다. 질환의확진후일차적인치료는보존요법이다. 12 원인인자가있는경우원인인자제거가선행되어야하며항소염제, 항히스타민, 스테로이드사용으로좋은치료효과를기대할수있고, 항생제사용은요로감염이동반되었을경우도움이된다. 3,4,9,11 다른치료로는 dimethylsulfoxide, cyclosporin-a, 질산은등으로방광세척을시행한보고들이있다. 13,14 외과적치료는대부분의환자에서내시경하병변절제술로만족할만한치료효과를얻을수있다. 12 그러나질환의진행정도가심한환자에서는방광절제술, 회장을이용한방광확대술 15 등을고려할수있다. 저자들은전례에서항생제와항소염제, 호산구혈증이있었던 3례에서는스테로이드를투여하였다. 외과적치료는내시경하병변절제술이외에다른수술은시행하지않았다.

5 82 대한요로생식기감염학회지 : 제 2 권제 1 호 2007 년 5 월 호산구성방광염의경과가환자의과거력에따라다양하며, 재발및만성화의위험이있으므로적절한혈액및요검사, 방사선검사, 내시경검사를통한추적관찰이추천된다. 그러나추적관찰기간에대한의견은일치되지않고있다. 3 본연구에서환자의증상소실은약물투여후 2주이내소실되었고, 평균 5개월의추적관찰기간동안방광경을포함한혈액및요검사에서질환의재발이확인된례는없었다. 그러므로저자의견해는반드시모든환자가장기추적관찰이필요한지는의문이다. 이에대해서는추후많은환자를대상으로하는연구가필요하다고생각된다. 결 여자에비해상대적으로남자에서호산구성방광염의발생빈도가높았고, 내원당시증상으로는혈뇨와방광자극증상이가장많았다. 임상경과는양호하였으며, 병변절제술과약물치료의병행요법으로만족할만한치료효과를기대할수있다고생각된다. 론 REFERENCES 1. Brown EW. Eosinophilic granuloma of the bladder. J Urol 1960;83: Hellstrom HR, Davis BK, Shonnard JW. Eosinophilic cystitis: a study of 16 cases. Am J Clin Pathol 1979;72: Van den Ouden D. Diagnosis and management of eosinophilic cystitis: a pooled analysis of 135 cases. Eur Urol 2000;37: Choi SE, Choi HS, Kwak DH, Choo KW. Eosinophilic cystitis. Korean J Urol 1967;008: Frensilli FJ, Sacher EC, Keegan GT. Eosinophilic cystitis: observations on etiology J Urol 1972;107: Rubin L, Pincus MB. Eosinophilic cystitis: the relationship of allergy in the urinary tract to eosinophilic cystitis and the pathophysiology of eosinophilia. J Urol 1974;112: Dubucquoi S, Janin A, Desreumaux P, Rigot JM, Copin MC, Francois M, et al. Evidence for eosinophil activation in eosinophilic cystitis. Eur Urol 1994;25: Kang JS, Koo JW, Lee CK, Rhew HY. A case of eosinophilic cystitis presenting as invasive bladder cancer. Korean J Urol 1999;40: Itano NM, Malex RS. Eosinophilic cystitis in adults. J Urol 2001;165: Flamm J. Tumor associated tissue inflammatory reaction and eosinophilia in primary superficial bladder cancer. Urology 1992;40: Marshall FF, Middleton AW. Eosinophilic cystitis. J Urol 1974;112: Teegavarapu PS, Sahai A, Chandra A, Dasgupta M, Khan MS. Eosinophilic cystitis and its management. Int J Clin Pract 2005;59: Sibert L, Khalaf A, Bugel H, Sfaxi M, Grise P. Intravesical dimethyl sulfoxide instillations can be useful in the symptomatic treatment of profuse hematuria due to eosinophilic cystitis. J Urol 2000;164: Pomeranz A, Eliakim A, Uziel Y, Gottesman G, Rathaus V, Tepper R. Eosinophilic cystitis in a 4 year old boy: successful treatment with cyclosporin A. Pediatrics 2001;108: Cardini S, Smulevich E, Salvadori A, Lombardi M. Augmentation ileocystoplasty in a case of eosinophilic cystitis. Minerva Urol Nefrol 1997;49:219-23

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