Original Article http://dx.doi.org/10.3947/ic.2012.44.5.362 Infect Chemother 2012;44(5):362-366 pissn 2093-2340 eissn 2092-6448 Infection & Chemotherapy 골반염과 Fitz-Hugh-Curtis syndrome 환자에서 N. gonorrheaee 및 C. trachomatis, U. urealyticum, M. hominis 의빈도 이경훈 1 김혜지 1 박철희 2 전윤정 1 최현정 1 이한나 1 조숙 1 서울의료원산부인과 1, 방사선과 2 Frequency of N. gonorrheaee, C. trachomatis, U. urealyticum and M. hominis in elvic Inflammatory Disease and Fitz-Hugh-Curtis Syndrome Background: elvic inflammatory disease (ID) is a common genital tract infection in reproductive women. This study aimed to determine the frequency of Neisseria gonorrheae, Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis in elvic inflammatory disease (ID), and to further sub-analyze the clinical characteristics in patients diagnosed with Fitz-Hugh-Curtis syndrome (FHCS). Material and Methods: Sixty-six patients diagnosed clinically as ID were recruited from April, 2007 to February, 2011. Retrospective chart review was per formed for investigating the characteristics of the clinical manifestation, laboratory findings, and image findings. And then all subjects were classified into two groups, the ID-only group and the, depending on whether or not computed tomography showed increased perihepatic enhancement. Samples obtained in endocervical swabs were tested using Roche COBAS Amplicor olymerase-chain reaction (CR) for N. gonorrheae, C. trachomatis, U. urealyticum, and M. hominis. Results: The 66 ID patients ranged in age from 19 to 49 years. Thirty nine patients were diagnosed as having an inflammation localized only in the lower abdomen (ID only), and 27 patients were diagnosed as FHCS. According to results of CR, U. urealyticum was found most commonly in both the and the FHCS group (66.7% and 59.3%, respectively). Conclusions: Organisms other than C. trachomatis and N. gonorrheae, particularly U. urealyticum, may be detected more frequently in ID patients in Korea. In addition, identification of M. hominis may be of importance in female health problems such as FHCS. Key Words: elvic inflammatory disease, Fitz-Hugh-Curtis Syndrome, Ureaplsama urealyticum, Mycoplasma homini 서론 골반염 (pelvic inflammatory disease, ID) 은하부생식계로부터미생물이상 Gyoung Hoon Lee 1, Hye Ji Kim 1, Chul Hi ark 2, Yoon Jung Chun 1, Hyun Jung Choi 1, Han Na Lee 1, and Sook Cho 1 Department of Obstetrics and Gynecology 1, Seoul Medical Center; Department of Radiology 2, Seoul Medical Center, Seoul, Korea 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) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2012 by The Korean Society of Infectious Diseases Korean Society for Chemotherapy Submitted: March 1, 2012 Revised: June 21, 2012 Accepted: July 6, 2012 Correspondence to Lee Gyoung Hoon, M.D. Department of Obstetrics and Gynecology, Seoul Medical Center, Seoul 131-130, Korea Tel: +82-2-2276-8916, Fax: +82-2-3410-8082 E-mail: ghleeobgy@gmail.com
http://dx.doi.org/10.3947/ic.2012.44.5.362 Infect Chemother 2012;44(5):362-366 363 행감염을일으켜자궁내막및난관, 난소에염증이발생하는질환으로자궁내막염및자궁관염, 난소염등을통상칭한다. 이에반해 Fitz- Hugh-Curtis 증후군 (FHCS) 은 ID 환자가간주위염 (perihepatitis) 을동반한경우로 3-10% 정도의유병률을보인다고알려져있다 [1]. 골반염의일반적인진단기준은 2006년미국질병관리본부의가이드라인을따르나 [2], 실제임상에서 ID를정확하게진단하기는역부족인경우가많다 [3]. 또한진단방법으로복강경시술을이용하는방법이제기되었으나침습적시술이면서고비용이라는제한점이존재한다 [4]. 보조적방법으로주원인균에대한빈도조사도임상에서활발히시행되고있는데, ID의주요원인균으로알려진 Chlamyida trachomatis 과 Neisseria gonorrheae 은물론 Mycoplasma hominis 과 Ureaplasma urealyticum 에대한검사가바로그것이다. 그러나, 이들균의발견빈도에대해서는연령에따라또는지역에따라서로다르다. 예를들어 Sorbye 등 [5] 은 10 대젊은여성에서발생한 ID에서는 C. trachomatis 가많이발견되지만나이가든여성에서는유병률이감소한다고보고한적이있으며, 이에반해임질균에의한 ID 유병률은점점줄어들고있다는보고도있다 [6]. Cho 등 [7] 은 ID의약 70% 에서원인균이밝혀지지않았다고보고한바도있다. 또한영상진단방법으로는근래에들어임상에서쉽게접근할수있다는장점때문에질식초음파를이용하는방법이있으나초기 ID의경우정상소견으로보일수있고특징적인초음파소견이없다는위음성의가능성이단점으로작용한다 [8]. 이와는달리전산화단층촬영 (computed tomography, CT) 의경우, 비침습적인방법이면서초음파에서진단하기어려운초기염증단계에서도진단이가능하며동시에복통을주소로한환자들의감별질환을동시에할수있다는장점을가지고있어널리쓰이고있다 [9, 10]. 이에본저자들은임상적진단기준과 CT 촬영소견상 ID나 FHCS 로진단된환자군에서 C. trachomatis 와 N. gonorrheae, 비특이적균인 M. hominis 과 U. urealyticum 의빈도를비교하고, 이후발견된원인균에따른임상양상, 영상검사소견차이를확인하고자하였다. 재료및방법 본연구는후향적의무기록조사연구로 2007 년 4월부터 2011 년 2 월까지본원산부인과에서임상진단기준과복부 CT를통해 ID 진단을받은 66명의환자를대상으로하였으며, 본원의연구윤리심의위원회의승인을받았다. 골반염은미국질병통제예방센터 (CDC) 에서규정한최소진단기준에의거하여외래나응급실에서하복통과내진시자궁과자궁부속기압통, 자궁경부요동시압통을보인경우에진단하였다 [2]. 대상환자군의나이와교육정도, 산과력, 자궁내피임장치의유무를의무기록을통해조사하였고, 환자의주관적인증상인하복부동통, 우측상복부동통, 열감, 오심또는구토, 상복부통증, 설사를동반한위장장애유무와골반내진검사상양측부속기와자궁경부요동시압통과같은객관적증상유무, 내원당시백혈구수치를포함한일 반혈액검사결과와자궁경부내원인균결과내용을확인하였다. 당시자궁경부내원인균검사는다음과같은방식으로시행되었다. 우선산부인과전문의나전공의가채집솔 (cytobrush) 를이용하여자궁내경부 (endocervical) 세포를얻은후해당세포를 ph 7.4 의무균완충생리식염수에재빨리담아녹십자에 C. trachomatis, N. gonorrheae, M. hominis, U. urealyticum 에대한 olymerase-chain reaction (CR) 검사를의뢰하였다. 후향적의무기록조사당시환자의 CR 결과를재확인하기위해 3명의환자를임의선별하여해당환자의이전 CR 검사결과를고지하지않고녹십자에재검사를의뢰하여, 이전결과와일치된소견을확인하였다. 이후최소진단기준에따른 ID 소견만을보이는경우를 ID 환자군 으로하였고, ID의임상증상을보이면서우상복부통증과전산화단층촬영에서간피막조영증가소견을보이는 FHCS 환자군 로분류한후비교분석하였다. 복부 CT 검사는환자들에게촬영에관한동의서를얻은후 SIEMENS Somatoms Sensation 16 channel 을이용하여두미방향 (craniocaudal direction) 으로촬영하였으며, 조영제 Ultravist 300을초당 3 ml의속도로전주와정맥 (antecubital vein) 에자동펌프기를통해주입하였다. 동맥기촬영을위해조영제투여후 0-30 초후재촬영, 문맥기촬영을위한 70초후재촬영, 지연기촬영을위한 180 초후재촬영을시행하였고, 영상의학과소속의사 2인이다음의소견 ( 골반부종을보이는경우또는자궁경부 / 난소 / 난관충혈이보이는경우, 두꺼워진난관이나조영증강소견이보이는경우, 난관 / 난소농양을보이는경우 ) 이있는경우 ID라진단하였다 [9]. 동일한 CT 소견에서골반염증소견을보이면서동맥기에간피막조영증강을보이는경우에 FHCS 으로진단하였으며, 직접적인간실질침범이있는경우는진단에서제외하였다 [11]. 후향적의무기록조사시모든 66명 ID 환자의복부 CT 판독을 1 인의영상의학과전문의에게재판독을의뢰하여해당환자의 CT 소견을다시확인하였고, 당시원인균에대한정보는제공하지않았다. 통계학적결과분석은 SSS ver. 17.0 (SSS Inc., Chicago, IL, USA) 을이용한 Student's t-test 및 Chi square test 를시행하였고, 기대빈도가 5보다작은경우가 20% 이상인경우 Fisher's exact test 를시행하였다. 값이 0.05 미만인경우를통계학적으로유의하다고판정하였다. 결과 ID 또는 FHCS 진단은 19-29 세연령군에서주로이루어졌으며, 고졸이상의교육정도를보인경우가많았으나두그룹사이에통계적차이는보이지않았다. 또한산과력과자궁내피임장치 (intrauterine device, IUD) 유무도두군사이에유의한차이를보이지않았다 (Table 1). 하복부와부속기통증, 자궁경부요동시압통과같은증상은두그룹모두에서비슷한빈도로발견되었으나, 우측상복부통증은 FHCS
364 GH Lee, et al. Frequency of the Causative Organisms in ID and HCS Table 1. Baseline Characteristics of Women Diagnosed as the ID-only Group and the FHCS Group 환자군에서 ID 환자군보다높은빈도를보였다 (55.6% vs. 10.3%, <0.001) (Table 2). Baseline characteristics Age 19-29 y 26 66.7 21 77.8 0.639 30-49 y 13 33.3 6 22.2 Education high school graduate 10 25.6 6 22.2 0.750 >high school graduate 29 74.4 21 77.8 Live birth 0 32 82.1 23 85.2 0.737 1 7 17.9 4 14.8 Loop insertion Yes 1 2.6 4 14.8 0.149 No 39 97.4 23 85.2 ID, pelvic inflammatory disease; FHCS, Fitz-Hugh-Curtis syndrome. Table 2. Clinical Symptoms of Women Diagnosed as the ID-only Group and the FHCS Group Clinical characteristics Subjective symptoms Lower abdominal pain 30 76.9 19 70.4 0.549 RUQ pain 4 10.3 15 55.6 <0.001 Febrile sensation 4 10.3 2 7.4 1.000 GI complaint 7 17.9 6 22.2 0.668 Objective symptoms Cervical motion tenderness 24 61.5 12 44.4 0.170 Adnexa tenderness 30 76.9 21 77.8 0.935 Fever 0 0 2 7.4 0.164 RUQ, right upper quadrant; GI complaints, Gastro-intestinal complaints (i.e., nausea, vomiting, upper gastric pain and diarrhea) 진단당시혈액검사결과를두군에서비교해본결과, C- 반응성단 백질수치만이 FHCS 환자군에서통계적으로유의한상승수치를보였다 (0.94 mg/dl vs. 2.42 mg/dl, =0.015) (Table 3). 원인균이검출되지않은경우는총 19명 (28.8%) 이었으며이를제외한 47명의환자에서 U. urealyticum 이가장흔하게발견되었고 (63.6%), 이후 C. trachomatis 가 19.7%, M. homins 15.1%, N. gonorrheae 4.5% 순이었다 (Table 4). 2가지균이상이발견되는중복감염은각각 10 명 (ID 환자군 ) 과 6명 (FHCS 환자군 ) 이었으며, 중복감염은 U. urealyticum 과 C. trachomatis, U. urealyticum 과 M. hominis 이동시에감염된경우가각각 6명으로가장많았다. 대상환자 66명의복부 CT 방사선소견을골반부종또는난관염증소견, 난소주위염증변화 (periovarian stranding), 자궁내막조영증가가보이는경우로각각구분하고비교해본결과, U. urealyticum 균이발견된경우가장흔한 CT 소견으로골반부종소견이나타났 Table 3. Laboratory Characteristics of Women Diagnosed as the ID-only Group and the FHCS Group 으며 (38 명, 90.5%) 이후난관염증소견 (20 명, 47.6%), 난소주위염증변화 (20 명, 47.6%), 자궁내막조영증가소견 (8명, 19.6%) 순이었다. 이와는달리, C. trachomatis 은 U. urealyticum 균에비해난관염증소견 (8명, 61.5%) 및난소주위염증변화 (7명, 53.8%) 가좀더높은빈도로보였으나, 통계적으로유의하지않았다. M. hominis 균과 N. gonorrheae 균은발현빈도가낮아통계에서제외하였다. 고찰 Laboratory characteristics mean SD mean SD Inflammatory marker WBC 7,130 2,784 7151 3,923 0.981 CR 0.94 1.64 2.42 2.71 0.015 T.bil. 0.9 1.0 0.9 1.4 0.939 ALT 13.5 7.5 12.5 6.1 0.542 AST 19.0 6.5 20.5 11.9 0.519 AL 55.3 14.1 57.7 20.0 0.573 WBC, white blood cell count (/mm 3, 4,000-10,000); CR, C-reactive protein (mg/dl, 0.0-0.4); T.bil., total bilirubin (mg/dl, 0-1.3); ALT, Alanine transaminase (U/L, 0-40); AST, Aspartate transaminase (U/L,0-40); AL, Alkaline phosphatase (U/L, 30-125) Table 4. The revalence of Causative Organisms of Infection in Women Diagnosed as the ID-only Group and the FHCS Group ID-only grroup (N=39) (N=27) Total (N=66) CR (+) U. urealyticum 26 66.7 16 59.3 42 (63.6%) 0.539 C. trachomatis 5 12.8 8 29.6 13 (19.7%) 0.091 M. hominis 3 7.7 7 25.9 10 (15.1%) 0.077 N. gonorrheae 1 2.6 2 7.4 3 (4.5%) 0.563 본연구에서는임상적진단기준과복부 CT로진단된 ID 환자군 39명과 FHCS 환자군 27명을대상으로의무기록을후향적으로조사하여, ID 환자에서발견되는원인균의양성률을얻고이에따른흔한원인균을유추하고자하였다. 일반적으로 ID 환자에서 N. gonorrheae, C. trachomatis, M. hominis, U. urealyticum 가각각어느정도의유병률을가지는지에관한연구는아직까지충분치않으며, ID 원인균들의분포에변화가있다는보고도발표되고있다 [7]. 2002년 EACH (elvic inflammatory disease evaluation and clinical health) 연구결과를보면 [12], C. trachomatis 균과 N. gonorrheae 균이발견되는경우는 14-15% 정도에불과하고 ID의약 70% 에서는원인균이밝혀지지않았다고보고한바가있다. 과거이처럼원인균을발견할수없는이유로는잠재적원인균으로알려진 M. hominis 및 U. urealyticum 균을동정하기어려웠기때문이라생각되는데, 1937 년바르톨린농양으로부터처음분리되어보고된 M. hominis 은일반한천배지에서발육하지
http://dx.doi.org/10.3947/ic.2012.44.5.362 Infect Chemother 2012;44(5):362-366 365 않고특수배지에서만배양되는까다로운성질로정확한검출이어렵다고알려져있다 [13, 14]. 또한건강한성인뿐만아니라사춘기전여아에서도해당균들이발견된다고알려져 1970 년대까지비병원성균으로간주되기도하였다 [15]. 그러나본연구결과를통해알수있듯이, 비병원성이라알려졌던 U. urealyticum 와 M. hominis 가전체 66명의환자군중 52명의환자 (78.7%) 에서나발견되었으며 C. trachomatis 가검출된 13예에불과하였고 N. gonorrhea 은단지 3예에서만검출되었다는사실은 ID의약 70% 에서는원인균이밝혀지지않았다는보고와함께주목할만하다고하겠다. Zhou 등 [16] 은급성 ID 환자 130 명을분석한결과 C. trachomatis 4.6% (6/130), N. gonorrheae 6.9% (9/130), U. urealyticum 37.7% (49/130) 이라고보고하였고, Rodrogues 등 [17] 은급성 ID 여성환자 224 명중 C. trachomatis 10.8% (7/65), N. gonorrheae 9.2% (6/65), M. hominis 38.5% (25/65), Ureaplasma spp. 53.8% (35/65) 라고보고한바가있다. 이두연구모두 ID의주요원인균으로서 U. urealyticum 의빈도가가장높았음을알수있으며, 이는본연구의결과와유사하다고할수있겠다. Nunez-Troconis 등 [18] 은성교대상자가많을수록조기성경험자일수록 U. urealyticum 및 M. hominis 가많이발견된다고하면서해당균의병원성과 ID와의연관성을보고한적이있으며, Grzesko 등 [19] 도성생활이활동적인여성에게해당균들이많이발견된다고하면서병원성을언급한바가있다. U. urealyticum 균과 M. hominis 균은 ID뿐아니라 [20, 21], 비임균성요도염 [22], 불임 [23], 습관성유산 [24], 저체중아출산 [25], 양막염, 조기양막파수 (premature rupture of membrane)[26] 및조산 [27] 에서연관성이있다고보고된바있다. 본연구에서가장많이발견된 U. urealyticum 균의특징적인 CT 소견을확인하기위해 1인의영상의학과전문의에게발견된원인균에대한정보를제공하지않고복부 CT 판독을재의뢰하여 U. urealyticum 균양성환자의 CT 소견을 C. trachomatis 균양성환자의 CT 소견과비교분석해보았다. 비교분석해본결과, U. urealyticum 양성환자군의복부 CT 소견은정형적인 ID 소견을보였으나 C. trachomatis 환자군은난관염증및난소주위염증변화소견을더많이보였다. 결론적으로본연구는 ID 여성환자를대상으로한 C. trachomatis, N. gonorrhea, M. homonis, U. urealyticum 균에대한빈도조사로서 U. urealyticum 및 M. hominis 균감염이기존성병이나 C. trachomatis 균에못지않은중요성을가질수있음을제시하고있다고하겠다. 그러나, 본연구디자인이전향적무작위대조군연구가아니라는점그리고본원에내원하기전항생제에노출된과거력을조사하지않는점, 환자군이 66명으로비교적소수라는점은여전히임상적용의제한변수로작용하고있으므로향후보편적인합의를위해서는좀더많은환자군을대상으로한전향적관찰연구가필요할것으로사료된다. References 1. Holmes KK, Handsfield HH. Sexually transmitted disease: overview and clinical approach. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison's principles of internal medicine. 16th ed. New York: McGraw- Hill; 2004;770. 2. Center for Disease Control and prevention, Workowski KA, Berman SM. Sexually transmitted disease treatment guidelines, 2006. MMWR Recomm Rep 2006;55:1-94. 3. Holmes KK, Sparling F, Mardh A, Lemon SM, Stamm WE, ilot, Wasserheit JN. Sexually transmitted disease. 3rd ed. New York: McGraw-Hill; 1998;738-809. 4. Hager WD. Follow-up of patients with tubo-ovarian abscess (es) in association with salpingitis. Obstet Gynecol 1983;61: 680-4. 5. Sørbye IK, Jerve F, Staff AC. Reduction in hospitalized women with pelvic inflammatory disease in Oslo over the past decade. Acta Obstet Gynecol Scand 2005;84:290-6. 6. Simms I, Eastick K, Mallinson H, Thomas K, Gokhale R, Hay, Herring A, Rogers A. Association between Mycoplasma genitalium, Chlamydial trachomatis and pelvic inflammatory disease. J Clin athol 2003;56:616-8. 7. Cho MK. Update on the management of pelvic inflammatory disease. Korean J Obstet Gynecol 2010;53:961-6. 8. atten RM, Vincent LM, Wolner-Hanssen, Thorpe E Jr. elvic inflammatory disease. Endovaginal sonography with laparoscopic correlation. J Ultrasound Med 1990;9:681-9. 9. Sam JW, Jacobs JE, Birnbaum BA. Spectrum of CT findings in acute pyogenic pelvic inflammatory disease. Radiographics 2002;22:1327-34. 10. Jung SI, Kim YJ, ark HS, Heon HJ, Jeong KA. Acute pelvic inflammatory disease: diagnostic performance of CT. J Obstet Gynaecol Res 2011;37:228-35. 11. Joo SH, Kim MJ, Lim JS, Kim JH, Kim KW. CT diagnosis of Fitz- Hugh and Curtis syndrome: value of arterial scan. Korean J Radiol 2007;8:40-7. 12. Ness RB, Soper DE, Holley RL, eipert J, Randall H, Sweet RL, Sondheimer SJ, Hendrix SL, Amortegui A, Trucco G, Songer T, Lave JR, Hillier SL, Bass Dc, Kelsey SF. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the pelvic inflammatory disease evaluation and clinical health (EACH) Randomized trial. Am J Obstet Gynecol 2002;186:929-37. 13. Boom R, Sol CJ, Salimans MM, Jnsen CL, Wertheim van Diller M, van der Noordaa J. Rapid and simple method for purification of nucleic acids. J Clin Microbiol 1990;28:495-503. 14. Blanchard A, Henschel J, Duffy L, Baldus K, Cassel GH. Detection of Ureaplasma urealyticum by polymerase chain reaction in the urogenital tract of adult, in amniotic fluid, and
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