대한내과학회지 : 제 88 권제 5 호 2015 http://dx.doi.org/10.3904/kjm.2015.88.5.612 식도 - 종격동누공이동반된비결핵성마이코박테리움감염 1 예 부산대학교의학전문대학원양산부산대학교병원내과 안은영 김은정 류대곤 최유희 김태현 이수진 Case of Nontuberculous Mycobacterium Infection Complicated by an Esophagomediastinal Fistula in a Human Immunodeficiency Virus Patient EunYoung hn, EunJung Kim, DaeGon Ryu, YuHee Choi, TaeHyun Kim, and SuJin Lee Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea n esophagomediastinal fistula is rare complication of nontuberculous mycobacterium infection. Here, we report the case of a patient with advanced acquired immunodeficiency syndrome who presented with a fever, cough, and dyspnea, and was eventually diagnosed with nontuberculous mycobacterium infection. Computed tomography revealed multiple lymphadenopathy with an esophagomediastinal fistula. The patient was treated with anti-mycobacterial medications and endoscopic fistula closure. (Korean J Med 2015;88:612-616) Keywords: Human immunodeficiency virus; Mycobacterium infections, Nontuberculous; Esophageal fistula 서론 Human immunodeficiency virus (HIV) 감염은숙주의 CD4 양성 T세포의기능적이상및수적감소를초래하여면역약화로인한여러가지기회감염을일으키는질환이다 [1]. 1980년대후천성면역결핍증 (acquired immnuodeficiency syndrome, IDS) 환자에게서비결핵성마이코박테리움 (nontuberculous mycobacterium, NTM) 감염이처음보고된이후 IDS 환자에게서 NTM의발병률은높아졌다 [2]. Mycobacterium lentiflavum과 Mycobacterium genavense는 NTM 중에서흔하지않으나주로면역저하자에게질병을일으키는것으로보고되고있다 [3-7]. 본저자들은 HIV 환자에서 NTM (M. lentiflavum 또는 M. genavense) 에의해발생한식도- 종격동누공을수술적치료를하지않고약물치료및내시경적시술을이용하여성공적으로치료하였기에보고하는바이다. Received: 2014. 5. 20 Revised: 2014. 6. 23 ccepted: 2014. 8. 4 Correspondence to SuJin Lee, M.D. Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan 626-770, Korea Tel: +82-51-360-2120, Fax: +82-51-360-2122, E-mail: beauty192@hanmail.net Copyright c 2015 The Korean ssociation of Internal Medicine This is an Open ccess article distributed under the terms of the Creative Commons ttribution - 612 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- EunYoung hn, et al. NTM infection with esophageal fistula - 증례환자 : 29세남자주소 : 발열, 호흡곤란현병력 : 1개월전부터발열로 HIV를진단받고 1주일전부터항레트로바이러스약물복용중이던상태로발열이지속되고우측흉부통증및호흡곤란으로입원하였다. 과거력 : 입원 1주일전 HIV가진단되어항레트로바이러스약물 (tenofovir, emtricitabine, efavirenz) 및 trimethoprim-sulfamethoxazole (TMP-SMX) 복용중이었다. 사회력 : 15갑년의흡연력가족력 : 특이사항이없음. 신체검사소견 : 신장 173 cm, 체중 68 kg, 내원시혈압 110/70 mmhg, 맥박및호흡수 104회 / 분, 20회 / 분이었으며체온은 38.5 였다. 의식은명료하였고급성병색소견을보였다. 검사실소견 : 입원당시말초혈액검사에서백혈구 7,970 /mm 3 ( 중성구 78.2%), 헤모글로빈 14.3 g/dl, 혈소판 246,000 /mm 3, CD4 양성 T세포수 37/uL였고 HIV ribo-nucleic acid (RN) 는 67,400 copies/ml 였다. 일반화학검사에서크레아티닌 0.95 mg/dl, 아스파테이트아미노전이효소 (aspartate transaminase, ST) 47 IU/L, 알라닌아미노전이효소 (alanine transaminase, LT) 70 IU/L, 알칼라인포스파타아제 (alkaline phosphatase, LP) 380 IU/L, 총빌리루빈 0.4 mg/dl, C 반응성단백 (C-reactive protein, CRP) 5.83 mg/dl 였다. 치료및경과 : 입원당시시행한단순흉부촬영에서기흉소견으로흉관을삽입했고흉부전산화단층촬영에서우측쇄골상부및종격동림프절종대소견을보여 (Fig. 1) 입원 6 일째비디오흉강경수술 (video-assisted-thoracoscopic surgery, VTS) 로종격동림프절조직검사를시행하였다. 이후기흉이호전되어흉관을제거하였고발열이호전되어퇴원하였다. 외래에서조직검사결과를확인할예정이었으나퇴원 2 주뒤발열, 호흡곤란으로병원을방문했고단순흉부촬영에 Figure 1. The initial chest computed tomography revealed enlargement of multiple lymph nodes (arrows). Figure 2. () Chest computed tomography showed a tree-in-bud appearance with clusters of centrilobular nodules. () The periesophageal gas collections from enlarged paraesophageal lymph nodes suggest the presence of an esophago-nodal (esophagomediastinal) fistula. - 613 -
- 대한내과학회지 : 제 88 권제 5 호통권제 657 호 2015 - 서우측상부에종괴로보이는부분이있어추적흉부전산화단층촬영을시행하였다. 흉부전산화단층촬영에서전반적으로림프절들의크기가증가하였고분기상음영 (tree-inbud appearance) 이새로관찰되어활동성결핵이의심되었으며중부식도와인접한림프절종대와누공이의심되었다 (Fig. 2). 이전입원당시시행한림프절조직검사결과에서는만성육아종성염증소견이확인되었으나 (Fig. 3) 황산성염색도말검사 (acid-fast bacilli stain, F stain) 나결핵균배양검사는음성이었다. 하지만객담 F 도말검사에서양성반응이나와폐결핵에준해표준 4제요법을시작하였다. 재입원 9일째누공확인을위해시행한상부내시경검사 에서다소깨끗한경계를지닌함몰된병변에미세한구멍이관찰되었고 (Fig. 4) 식도조영술에서는중부식도의전면으로조영제누출이관찰되어식도종격동누공을진단하였다 (Fig. 5). 한달여간금식및약물치료를하면서경과관찰하였으나추적흉부전산화단층촬영에서누공의호전이없어내시경을통해 clipping을시행하였다 (Fig. 4). 식도 clipping 시행후식도조영술에서조영제누출이보이지않아 clipping 이후 6일째부터경구섭취하며경과관찰하였다. 객담배양검사에서재입원 21일째 NTM이자라는것이확인되어대한결핵협회로동정을의뢰하였고재입원 46일째 dvansure Mycobacteria Genolot ssay kit (LG Figure 3. Histopathologically, chronic granulomatous inflammation of the lower paratracheal lymph nodes (arrows). () H&E stain, 12.5. () H&E stain, 100. Figure 4. () Esophagoscopy revealed the fistula orifice (arrow). () One month later, the fistula was closed endoscopically with clips. - 614 -
- 안은영외 5 인. 식도 - 종격동누공이동반된 NTM 감염 - Figure 5. () Esophagography revealed slit-like extraluminal contrast leakage anterior to the mid-esophagus (arrows). () t the 1-year follow-up, esophagography showed no contrast leakage. Table 1. Drug susceptibility results of Mycobacterium lentiflavum/mycobacterium genavense ntibiotics Minimum inhibitory concentration (MIC, μg/ml) mikacin 1 Cefoxitin 32 Ciprofloxacin 0.25 Clarithromycin 0.5 Doxycycline 4 Ethambutol > 32 Imipenem 16 Linezolid 2 Moxifloxacin 0.125 Rifampin 0.5 Tobramycin 2 Trimethoprim/Sulfamethoxa 10 Life Sciences, Seoul, Korea) 에의해최종적으로 M. lentiflavum 또는 M. genavense인것으로확인되었으나추가적인 sequencing은이루어지지않았다. 약제감수성검사에근거하여 amikacin (4주사용 ), moxifloxacin, clarithromycin, rifampicin으로투여를시작하였다 (Table 1). Clipping 시행 1년뒤에시행한식도조영술에서 clip이다제거된상태이나조영제누출은관찰되지않았다 (Fig. 5). 식도-종격동누공진단이후 1년정도된현재까지약물치료를유지하고있으며증상악화없이유지되고있다. 고 HIV 감염은숙주의 CD4 양성 T 세포의기능적이상및수 찰 적감소를초래하여면역약화로인한여러가지기회감염을일으키는질환이다 [1]. 1980년대 IDS 환자에게서처음 NTM 감염이보고된이후 IDS 환자에서 NTM의발병률은높아졌다 [2]. 본환자의경우대한결핵협회에서 dvansure Mycobacteria Genolot ssay kit (LG Life Sciences) 에의해서균동정이이루어졌다. dvansure Mycobacteria Genolot ssay kit (LG Life Sciences) 는원-튜브네스티드다중비대칭중합효소연쇄반응 (one-tube nested multiplex asymmetric polymerase chain reaction [PCR]) 방법을이용한역교잡반응라인블롯어세이방식을이용하는것으로 NTM의 16S ribosomal RN (rrn) 와 23S rrn 사이에존재하는 Inter Transcriptional Spacer (ITS) 부위를비대칭적인 PCR 방법으로바이오틴부착마이코박테리아속프라이머를이용하여증폭시키고나일론멤브레인- 흡착프로브와교잡후효소접합반응을시킨후발색시켜판독카드와비교하여결과를해석하게된다. 이방식으로 M. lentiflavum 또는 M. genavense임을확인하였으나최종균동정을위한추가 sequencing은이루어지지않아한계점으로생각된다. M. lentiflavum 는지연성장항산성균 (slowly growing acid-fast bacteria) 으로 1996년처음 NTM으로분류되었고 M. genavense, Mycobacterium simiae 와함께 16S rrn 염기서열상매우유사함을보였다 [3]. M. lentiflavum 은흔하지않으나몇몇소아와면역억제자에서주로림프절염의형태로질병을일으키거나드물지만림프절이외기관에서질병을일으킨경우도보고되고있다. 치료의경우아직정해진치료방침은없으나경부림프절의경우수술적절제를하거나그외에는항 - 615 -
- The Korean Journal of Medicine: Vol. 88, No. 5, 2015 - 결핵제를조합하여치료하고있다 [4]. M. genavense도 1992 년 IDS 환자에서새롭게분류되었고면역저하환자에서다양한장기에주로파종성질병을일으킬수있다고보고되고있다 [5-7]. M. genavense의경우 amikacin, rifamycins, fluoroquinolones, streptomycin, macrolides 계열에주로감수성이있고특히 clarithromycin을포함한치료가더효과가있는것같다고알려져있으나치료방침이뚜렷하게정해져있지는않은상황이다 [7]. 식도-기관누공의경우대부분악성종양과관련있는경우가많으며식도- 기관누공환자중 5-6% 정도만양성누공인것으로생각되고있다 [8]. 양성식도누공의치료는명확한치료지침이없는상태로수술이나비수술적인치료를시도해볼수있다. 결핵성식도누공에대해 1987년국내에서약물치료만으로호전된경우를보고한적이있으며 [9] 최근에는식도누공에서내시경을이용한시술을시도해보고있는상황이다 [8]. 본환자에서처럼 NTM 감염에동반된식도- 종격동누공의경우약물치료에호전이없고수술의위험성이크다고판단되면상부내시경을통한 clipping을통해식이를시행하며경과를볼수도있을것으로생각된다. 또한 HIV 감염환자의경우기회감염예방을위해 CD4+ T세포수 50개이하시 Mycobacterium avium complex (MC) 감염예방을위해 azithromycin이나 clarithromycin의사용이권고되고있다 [10]. 하지만이환자의경우 CD4+ T세포수가단시간내회복될것으로기대하여이러한예방약제를사용하지않았고 NTM에감염되어합병증이동반되었다. 항레트로바이러스약물치료를하는 HIV 환자에서기회감염의예방을위해 CD4+ T세포가 50개이하시 azithromycin이나 clarithromycin의사용을꼭고려해야할것으로생각된다. 본저자들은면역저하자, 특히 HIV 환자에서 NTM에의해생긴식도- 종격동누공을수술적치료를하지않고약물치료와한번의내시경적 clipping 시술을이용하여성공적으로치료하였기에보고하는바이다. 요약 HIV 감염환자는여러기회감염에노출될수있다. NTM 은 IDS 환자에게기회감염을일으킬수있지만 NTM 감염 에동반된식도-종격동누공은흔하지않아치료방침이뚜렷하지않다. 본저자들은 IDS 환자에서 NTM 감염에동반된식도- 종격동누공을약물치료와내시경적시술을통해성공적으로치료하였기에보고하는바이다. 중심단어 : 인간면역결핍바이러스 ; 비결핵성마이코박테리움 ; 식도누공 REFERENCES 1. Fauci S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science 1988;239:617-622. 2. Falkinham JO. The changing pattern of nontuberculous mycobacterial disease. Can J Infect Dis 2003;14:281 286. 3. Springer, Wu WK, odmer T, et al. Isolation and characterization of a unique group of slowly growing mycobacteria: description of Mycobacterium lentiflavum sp. nov. J Clin Microbiol 1996;34:1100 1107. 4. Molteni C, Gazzola L, Cesari M, et al. Mycobacterium lentiflavum infection in immunocompetent patient. Emerg Infect Dis 2005;11:119-122. 5. öttger EC, Teske, Kirschner P, et al. Disseminated Mycobacterium genavense infection in patients with IDS. Lancet 1992;340:76-80. 6. Hoefsloot W, van Ingen J, Peters EJ, et al. Mycobacterium genavense in the Netherlands: an opportunistic pathogen in HIV and non-hiv immunocompromised patients. n observational study in 14 cases. Clin Microbiol Infect 2013; 19:432-437. 7. Griffith DE, ksamit T, rown-elliott, et al. n official TS/IDS statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. m J Respir Crit Care Med 2007;175:367 416. 8. hn JY, Jung HY, Choi JY, et al. enign bronchoesophageal fistula in adults: endoscopic closure as primary treatment. Gut Liver 2010;4:508-513. 9. Park JH, Moon JH, Kim JH, et al. case of tuberculous tracheoesophageal fistula. Korean J Med 1987;32:690-696. 10. Kaplan JE, enson C, Holmes KK, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine ssociation of the Infectious Diseases Society of merica. MMWR Recomm Rep 2009;58(RR-4):1-207; quiz CE1-4. - 616 -