대한류마티스학회지 Vol. 17, No. 2, June, 2010 DOI:10.4078/jkra.2010.17.2.143 원저 피부근육염 / 다발근육염에서발생한자발종격동기종의임상적의미 한양대학교의과대학내과학교실 1, 한양대학교의과대학내과학교실류마티스병원 2 김진주 1 ㆍ김담 1 ㆍ김은경 1 ㆍ손일웅 1 ㆍ정경희 2 ㆍ최찬범 1,2 ㆍ성윤경 1,2 전재범 1,2 ㆍ엄완식 1,2 ㆍ김태환 1,2 ㆍ배상철 1,2 ㆍ유대현 1,2 =Abstract= Clinicial Significance of Spontaneous Pneumomediastinum in Dermatomyositis/Polymyositis Jin Ju Kim 1, Dam Kim 1, Eun Kyoung Kim 1, Il Woong Sohn 1, Kyong Hee Jung 2, Chan-Bum Choi 1,2, Yoon-Kyoung Sung 1,2, Jae-Bum Jun 1,2, Wan-sik Uhm 1,2, Tae Hwan Kim 1,2, Sang Cheol Bae 1,2, Dae Hyun Yoo 1,2 Department of Internal Medicine, College of Medicine, Hanyang University 1, Department of Internal Medicine, The Hospital for Rheumatic Diseases, College of Medicine, Hanyang University 2, Seoul, Korea Objective: Pneumomediastinum (PnM), a rare complication of dermatomyositis and polymyositis (DM/PM), is sporadic and has an unclear pathogenesis. PnM is almost always associated with interstitial lung disease (ILD), and is a poor prognostic factor in inflammatory myositis patients. We studied the prevalence of PnM in Korean DM/PM and its clinical significance. Methods: We retrospectively studied the medical records of 161 patients diagnosed with DM/PM meeting Bohan-Peter s criteria at Hanyang University Hospital for Rheumatic Diseases from 1995 to 2010. We collected following findings; demographic data, diagnosis, lung involvement, cause of death, and duration from diagnosis to death. Results: One hundred nineteen patients (73.9%) were DM and 42 patients (26.1%) were PM. Eighty three patients (51.6%) developed ILD at diagnosis or during follow up. Eighteen patients (11.2%) died because of ILD aggravation, infection, or malignancy. The mean duration from diagnosis to death was 11.5 months, with 10 patients (6.2%) dying from from ILD aggravation but none with spontaneous PnM. 6 patients (3.7%) presented with PnM, and it was associated < 접수일 :2010 년 4 월 27 일, 수정일 (1 차 :2010 년 5 월 10 일, 2 차 :2010 년 5 월 13 일 ) 심사통과일 :2010 년 5 월 13 일 > 통신저자 : 유대현서울시성동구행당동 7 한양대학교류마티스병원 Tel:02) 2290-9202, Fax:02) 2298-8231, E-mail:dhyoo@hanyang.ac.kr 143
대한류마티스학회지제 17 권제 2 호 2010 with ILD worsening in all cases. PnM resolved with O 2 inhalation, corticosteroids, and/or immunosuppressive agents after 11 weeks (mean) of therapy Conclusion: PnM is rare but associates with DM and aggravation of ILD. PnM does not usually cause fatalities and can be cured by appropriate therapy. Key Words: Pneumomediastinum, Dermatomyositis/polymyositis, Interstitial lung disease, Prognosis 서 론 대상및방법 피부근육염 / 다발근육염 (dermatomyositis/polymyositis) 은근골격, 피부, 내부장기등에영향을미치는전신적인염증성질환이다. 이환자들의약 10 22% 에서호흡근육을침범하여호흡저하를비롯하여폐렴, 간질폐질환 (interstital lung disease) 과같은호흡기증상을일으킬수있다 (1-3). 피부근육염 / 다발근육염환자에서간질폐질환이발생하면임상적으로나쁜예후를보인다고보고되어있다 (3). 종격동기종 (pneumomediastinum) 은종격동내에공기혹은다른가스가비정상적으로존재하는상태를말하며손상, 종격동염, 기계환기와같은원인에의해발생하지만특별한원인없이발생할수도있다 (4). 또한자발종격동기종은피부근육염 / 다발근육염, 전신홍반루푸스, 류마티스관절염, 혼합결체조직병등과같은전신류마티스질환에서드물게보고되고있다 (5-7). 피부근육염 / 다발근육염환자에서간질폐질환이발생하는빈도는 10 43% 정도로보고되고있으나자발종격동기종은전세계적으로드물게보고되고있다. 피부근육염 / 다발근육염환자에서종격동기종이발생한경우그예후가매우불량하여종종사망에이른경우도보고되어있으나 (8,9), 최근에 Kuroda 등과한국에서는이등이 cyclosporine 등을이용하여성공적으로치료된증례를보고하였으며 (10,11), 피부근육염환자에서종격동기종자체가나쁜예후인자는아니라는보고도있다 (12). 본연구에서는피부근육염 / 다발근육염환자에서자발종격동기종의발생빈도와임상적의미에대해고찰해보고자한다. 1. 연구대상 1995년 1월부터 2010년 3월까지한양대학교류마티스병원에입원및외래에내원한환자중에전산실을통해 ICD 10 진단코드 M33, M330, M331, M332, M339가들어간환자를조회하였다. 총 161명의환자가보한-피터씨진단기준 (Bohan-Peter s criteria) 에부합하여피부근육염 / 다발근육염으로진단받았다 (13). 조회한 161명의환자의무기록을후향적으로검토하였다. 임상적소견에대한조사는성별, 나이, 진단명, 추적관찰기간, 진단당시의 CK/LDH 수치, aldolase 수치, 항핵항체 (ANA) 와항 Jo-1, 간질폐질환과자발종격동기종과같은폐침범소견, 악성종양과같은합병증동반여부, 치료와현재상태, 사망한환자의경우사망의원인에대해조사하였다. 2. 간질폐질환의방사선학적분류및경과모든환자는초기진단당시와입원할시, 또는외래에서단순흉부X선촬영을주기적으로시행하였다. 간질폐질환이나폐내에다른이상이발견되거나호흡곤란으로입원한환자의경우흉부고해상전산단층촬영을시행하였다. 그물성결절모양 (reticulonodular opacity), 선상 (linear opacity) 혹은젖빛유리음영 (ground-glass opacity), 벌집모양 (honeycombing), 견인기관지확장증 (traction bronchiectasis) 과같은모양을보인경우간질폐질환으로진단하였다. 간질폐질환은폐생검을통한병리학적소견으로분류를하는것이표준방법이나실제로본원에서폐생검을시행한경우가없었다. 이에따라방사선학적소견에따라주로기저와말초에반점, 그물성음영및벌집모양소견을보이는경우는특발폐섬유증 (idiopathic pulmonary fibrosis), 주로기저부의반점또는기관지 144
김진주외 : 피부근육염 / 다발근육염에서발생한자발종격동기종의임상적의미 주위경화를보이는경우는특발기질화폐렴 (bronchiectasis oblitrans with organizing, BOOP), 종종견인확장을동반하며선상음영을동반또는동반하지않는기저부에주로젖빛유리음영을보이는경우는비특이간질성폐렴 (non-specific interstitial pneumonitis, NSIP), 전반적인폐경화와젖빛음영을보이는경우는급성간질폐렴 (acute interstitial pneumonitis, AIP) 으로구분하였다 ( 표 1) (14). 또한추적관찰기간동안고해상전산단층촬영을통해간질폐질환의경과에대해서변화없는경우, 호전 / 악화를반복하며서서히진행하는경우와빠른악화의경우로구분하였다. 3. 자발종격동기종의진단자발종격동기종은전후와측면촬영을포함한단순흉부X선촬영에서종격동내흉골뒤나대동맥 또는다른구조의경계를따라서보이는가늘고수직의방사선투과성선이보이는경우진단하였다 (4). 단순흉부X선촬영에서자발종격동기종이진단이된경우흉부고해상단층촬영을시행하였고, 호전 / 악화여부를알기위해추적단순흉부X선촬영과흉부고해상단층촬영을시행하여초기의검사와비교하였다. 결과 1. 일반적인특징 161명의환자는 31명의남자와 130명의여자로구성되었다. 이들의평균진단나이는 43.2세 ( 범위 6 75 세 ) 이고, 그들의평균추적관찰기관은약 30.4개월 ( 범위 1 155개월 ) 이었다. 피부근육염환자는 119명 (73.9%), 다발근육염은 42명 (26.1%) 였다. 각각의남녀비율은 1:3.8과 1:6이었다. 진단당시평균나이는 Table 1. Classification and patterns of Interstitial lung disease Morphologic pattern Clinical diagnosis Histologic features Imaging features Usual interstitial Nonspecific interstitial Desquamative interstitial Respiratory bronchiolitis Organizing Diffuse alveolar damage Lymphoid interstitial Idiopathic pulmonary fibrosis Spatial and temporal heterogeneity, dense fibrosis, fibroblastic foci, honeycombing Nonspecific Spatially and temporally interstitial homogeneous lung fibrosis or inflammation Desquamative Diffuse macrophage interstitial accumulation in alveoli Respiratory bronchiolitisassociated interstitial lung disease COP, BOOP Acute interstitial Lymphoid interstitial Peribronchiolar macrophage accumulation, bronchiolar fibrosis; macrophages have dusty, brown cytoplasm Patchy distribution of intraluminal organizing fibrosis in distal airspaces; preservation of lung architecture; uniform temporal appearance; mild interstitial chronic inflammation Basal, peripheral predominance, often patchy, reticular abnormality, honeycombing Basal predominance, ground-glass abnormality, reticular abnormality Basal, peripheral predominance ground-glass attenuation; sometimes cysts Centrilobular nodules, ground-glass attenuation Ground-glass attenuation; consolidation basal, peripheral predominance Diffuse distribution, uniform temporal Diffuse, ground-glass attenuation, appearance, alveolar septal thickening consolidation due to organizing fibrosis, airspace organization, hyaline membranes Diffuse lymphoplasmacytic Ground-glass attenuation, cysts infiltration of alveolar septa COP: cryptogenic organizing, BOOP: bronchiectasis obliterans with organizing 145
대한류마티스학회지제 17 권제 2 호 2010 각각 43.6세 ( 범위 6 75세 ), 38.7세 (16 75세) 였다. 전체환자중에 13명 (8.1%) 에서추적관찰기간중에악성종양이발견되었다. 간질폐질환은 83명 (51.6%) 에서발견되었는데피부근육염에서 69명 (58.0%), 다발근육염에서 14명 (33.3%) 이었다 ( 표 2). 2. 예후전체환자중에 18명 (11.2%) 의환자가사망하였고진단부터사망까지의기간은평균 11.5개월 ( 범위 1 37개월 ) 이었다. 사망원인은간질폐질환의악화에의한호흡부전 (10명, 6.2%), 악성종양의합병증 (5명, 3.1%), 세균성감염 (3명, 1.9%) 이었다. 악성종양으로사망한환자들은각각난소암 (2명), 위암 (1명), 전이성흉선종 (1명), 자연살해 T세포림프종 (NK/T cell lymphoma)(1명 ) 이었다. 악성종양및패혈증쇼크로사망한환자들은모두간질폐질환소견은없었다 ( 표 2). 3. 간질폐질환의진단과경과간질폐질환은 83명 (51.6%) 에서발견되었다. 이중 5명의환자는영상자료가남아있지않아제외하였다. 78명은각각특발폐섬유증 14명 (17.9%), 특발기질화폐렴 30명 (38.5%), 비특이간질폐렴 25명 (32.1%), 급성간질폐렴 1명 (1.3%), 두가지이상이혼합된형태의간질폐질환 8명 (10.3%) 이었다 ( 표 3). 두가지이상이혼합된형태의간질폐질환의경우는특발기질화폐렴과비특이간질폐렴이혼재한경우가 7명 (9.0%), 특발폐섬유증과비특이간질폐렴이혼재한경우가 1 명 (1.3%) 이었다. 간질폐질환은 51명 (65.4%) 에서추적관찰기간동안큰변화가없었고, 17명 (21.8%) 에서호전과악화를반복하여서서히악화되었으며, 10명 (12.8%) 에서호흡기증상이생긴지 1달이내에매우빠르게악화되었고, 이경우에는모두사망하였다 ( 표 4). 4. 자발성종격동기종발생환자들의특징추적관찰기간동안 6명 (3.7%) 의환자에서 7회의자발종격동기종이발생하였다. 5명은처음부터피부근육염을진단받았으며 1명은다발근육염진단시에자발종격동기종이발생하였다가 9개월뒤피부발 Table 2. Characteristics of dermatomyositis/polymyositis patients Dermatomyositis Polymyositis Numbers of patients 119 (73.9%) 42 (26.1%) Mean age at diagnosis (years) 43.6 (6 75) 38.7 (16 75) Mean period of follow up (months) 26.6 (1 155) 32.6 (1 121) Female/Male 94/25 36/6 Interstitial lung disease 69 (42.9%) 14 (33.3%) Malignancy 11 (9.2%) 2 (4.8%) Death causes Interstitial lung disease Malignancy Sepsis 16 (13.4%) 9 4 3 2 (4.8%) 1 1 Table 3. Radiologic classification of interstitial lung disease IPF BOOP NSIP AIP Mixed Unknown Numbers Result Alive (PnM) Expire 14 14 0 30 26 (4) 4 25 23 (1) 2 1 0 1 8 4 (1) 4 5 5 0 IPF: idiopathic pulmonary fibrosis, BOOP: bronchiectasis obliterans with organizing, NSIP: non-specific interstitial pneumonitis, AIP: acute interstitial pneumonitis, PnM: pneumomediastinum 146
김진주외 : 피부근육염 / 다발근육염에서발생한자발종격동기종의임상적의미 진이발생하면서피부근육염으로진단이바뀌었고이때종격동기종이재발하였다. 평균나이는 47.6세 ( 범위 42 59세 ) 이며모두여자환자였다. 종격동기종발생당시 5명의환자에서 CK 수치는정상범위였고, LDH 수치는 1명외에는모두증가하였다. 항 Jo-1 항체는모두음성이었으며, 항핵항체는 3명의환자에서양성으로각각 speckled pattern (1명), cytoplasmic pattern (2명) 이었다. 1명은피부근육염진단 3개월후간질폐질환이발병하였고나머지환자들은피부근육염진단당시에간질폐질환을동반하고있었다. 4명은특발기질화폐렴, 1명은비특이간질성폐렴, 나머지 1명은특발기질화폐렴과비특이간질폐렴이혼재되었다. 자발종격동기종은모든경우에서간질폐질환이악화되었을때발생하였는데 4명에서 Table 4. Clinical course of interstitial lung disease among dermatomyositis/polymyositis patients 목과흉부에피하기종을동반하였다. 이들은자발종격동기종이발생하기전에스테로이드및면역억제제를복용하고있었다. 3명에서는기침, 가래를동반하였으며, 6명모두에서입원당시또는입원기간중에갑작스럽게악화한호흡곤란을호소하여단순흉부X선촬영을하였다. 그후단순흉부X선촬영및흉부고해상단층촬영을하여자발종격동기종의경과를추적하였다. 6명모두에서자발종격동기종발생이후에는고용량스테로이드를사용하였으며이와함께사용하고있던면역억제제의용량조절과함께산소치료를병행하였고 2명의환자에서인면역글로불린주사치료를시행하였다. 목과흉부에광범위한피하기종을동반한환자 1명에서칼라절개 (collar incision) 와짜내기 (squeezing) 를시행하여호전되었으며이환자는 9개월후재발하였으나사용하고있는스테로이드, No interval change Slow progression Rapid progression Unknown Numbers Result Alive (PnM) Expire 51 51 17 16 (6) 1 10 0 10 5 5 0 PnM: pneumomediastinum Table 5. Characteristics of 6 cases of spontaneous pneumomediastinum at dermatomyositis/polymyositis patients Age /sex CK LDH Aldo. ANA Anti Jo-1 CV ILD agg. Treatment before PnM PM/DM, time to PnM Treatment after PnM Recovery 59/F 24 142 18.4 (+)* ( ) ( ) (+) PDS DM, initial. Steroid pulse, CsA 5 month 51/F 32 305 5.4 ( ) ( ) ( ) (+) PDS, CsA, HCQ DM, 1 month Steroid pulse, CsA, O 2 2 month 42/F 166 267 37.6 (+) ( ) ( ) (+) PDS, CsA, HCQ DM, 2 years Steroid pulse, CsA, O 2 2 weeks 43/F 125 448 12.9 ( ) ( ) ( ) (+) PDS, CsA DM, 6 month IVIG, PDS, CsA, HCQ, O 2, 5 month 44/F recur 49 290 251 346 3.7 7.1 (+) ( ) ( ) (+) (+) PDS, AZA PDS, CsA PM, initial. DM, 1 week PDS, CsA, O 2, Collar incision Unaltered, O 2 2 month 1 month 54/F 26 122 7.1 ( ) ( ) ( ) (+) PDS, CsA DM, 1 year IVIG, O 2, PDS, Tacrolimus 2 weeks Aldo.: aldolase, CV: cutaneous vasculopathy, agg.: aggravation, PDS: prednisolone, CsA: cyclosporine A, HCQ: hydroxycloroquinolone, AZA: azathioprine, IVIG: intravascular immunoglobulin. *Speckled pattern 1:640, Cytoplasmic pattern 1:320, Cytoplasmic patthern 1:160 147
대한류마티스학회지제 17 권제 2 호 2010 Table 6. Comparison of clinical features between Interstitial lung disease patients with and without pneumomediastinum Pneumomediastinum (+) Pneumomediastium ( ) Numbers of patients 6 (7.1%) 77 (92.9%) Age 48.8 (42 59) 45.4 (27 75) Male/Female 0/6 14/63 DM/PM 6/0 63/14 Follow up duration (months) 22 (2 57) 30.3 (1 155) ANA (+) 3 (50%) 47 (61.0%) CK/LDH (mean) 101.7/268.7 596.4/358.3 고찰피부근육염 / 다발근육염은주로근육과피부를침범하는아직까지명확한원인이밝혀지지않은전신적인염증성결체조직질병이다. 피부근육염 / 다발근육염에서폐를침범하는경우에는전반적인폐포의손상, 폐혈관염, 감염성폐렴, 폐부종과종양등을일으킬수있다 (10). 간질폐질환은피부근육염 / 다발근육염환자의약 10 43% 에서발견되는가장흔한폐질환이다 (1-3). 피부근육염 / 다발근육염환자에서일반적으로흔한사망원인은종양, 감염과심장질환으로알려져있으나간질폐질환역시사망률에영향을미치는원인으로알려져있다. 강등은한국인피부근육염 / 다발근육염에서의간질폐질환유병율은 40.3% 였고, 이것이나쁜예후와관련이있다고보고하였다 (3). 또한김등은염증성근질환환자의생존율에대한예후인자연구에서고령, 치료기간과사망률간의관계는유의성이없고, 간질폐렴과악성종양은염증성근질환과관련하여통계적으로유의하게예후에영향을미친다고보고하였다 (15). 본연구에서도간질폐질환의유병율은피부근육염 / 다발근육염에서각각 58.0% 와 33.3% 로서기존의보고와큰차이는없었다. 사망의원인에있어서도간질폐질환이높은빈도를보였다. 피부근육염 / 다발근육염에동반한자발종격동기종은드물게보고되어있다. Schwarz 등이 1976년처음으로피부근육염환자에서자발종격동기종의발생을보고하였고 (16), 그이후로추가적인증례들이보고되었으며 Kono 등은피부근육염 / 다발근육염환자의약 8.3% 에서종격동기종이발생한다고하였다 (17). 본연구에있어종격동기종은전체환자의 3.7% 에서발생하였다. 그러나모든환자가피부근육염환자였음을감안하면피부근육염환자중 5.0% 에서발생하였다. 지금까지보고된몇몇연구에서는자발종격동기종발생후약 37.5 52.5% 의사망률을보인다고알려져있다 (8,18-20). Matsuda 등과 Jansen 등은종격동기종을동반한피부근육염 / 다발근육염환자 20명과 9명에서각각 55% 와 30% 의사망률을보였다고보고하였다 (8,21). 그렇지만본연구에서사망한증례가없어반드시나쁜예후를보인다고할수는없다. 피부근육염 / 다발근육염에서의자발종격동기종은상대적으로드물지만특징적인합병증으로아직까지는그기전이명확히밝혀지지않았다. 발생기전에는 3가지가설이있는데, 첫째는간질폐질환에의해폐가섬유화되면서폐포가변성되고폐막하수포 (subpleural cyst) 를형성하여이주머니가터지면서종격동기종이발생한다는가설이다 (21). 두번째로는 Cicuttinit 등이말하는혈관염이론이있다 (22). 이는혈관병증에의해점막경계 (mucosal barrier) 가파괴되면서종격동기종이발생한다는이론으로 Kono 등과 Tong 등은종격동기종이발생한환자군에서그렇지않은환자군에서보다피부혈관병증이많이이환된다는것을보고하여피부혈관병증과종격동기종간에명확한연관관계가있음을보여주었다 (17,23). 마지막으로간질폐질환에스테로이드사용으로폐간질이약화됨으로인해종격동기종이발생한다는가설이있다 (9). Benoit Le Goff 등은근육약화가없고초기에폐기능검사에서일산화탄소확산능력 (DLCO) 또는폐용적 (vital capacity) 감소가심한폐침범이있는환자에서고용량스테로이드를 148
김진주외 : 피부근육염 / 다발근육염에서발생한자발종격동기종의임상적의미 Table 7. Review of reported spontaneous pneumomediastinum cases with dermatomyositis/polymyositis in Korean Ref. Age /Sex CK Aldolase Anti Jo-1 CV ILD agg. Treatment before PnM PM/DM, time to PnM Treatment after PnM Recovery 11 40/F 1,521 22.6 ( ) (+) (+) PDS, IVIG DM, 3 weeks Steroid IV, CsA, O 2 3 weeks 25 45/F NL? ( ) (+) (+) PDS, AZA, CPM DM, 2 months Unaltered 3 month 26 38/F 131 13.2 ( ) (+) (+) PDS, HCQ DM, 4 months Unaltered, O 2 1 month 27 18/M 4.6 13.8 ( ) ( ) (+) PDS, HCQ, IVIG DM, 1 months PDS, CPM, O 2, thoracostomy Expire (2 m.) 28 56/F 1,405? ( ) ( ) (+) PDS DM, 2 weeks PDS, O 2 Expire (1 m.) 29 53/F 20? ( ) ( ) (+) PDS, AZA DM,? Unaltered, O 2? 29 41/F 38? ( ) ( ) (+) PDS DM, 1 month PDS, AZA, O 2 2 weeks 30 36/F 73? ( ) (+) (+) PDS, MTX, HCQ DM, 4 months PDS, HCQ, MTX, IVIG, O 2 Expire (1 m.) 30 45/F 156? ( ) (+) (+) PDS, HCQ DM, 11 months Steroid IV, CsA IV, O 2 Expire (1 m.) Ref.: reference, CV: cutaneous vasculopathy, agg.: aggravation, NL: normal,?: unknown, PDS: prednisolone, CsA: cyclosporine A, HCQ: hydroxycloroquinolone, AZA: azathioprine, IVIG: intravascular immunoglobulin, M: month 사용한경우종격동기종발생후불량한예후와관련이있다고보고하였다 (24). 또한면역억제제의사용은예후와큰관련이없으나 50% 정도에서는회복을보였다고보고하였다 (24). 저자들은한국인피부근육염 / 다발근육염환자에서종격동기종이발생하여국내와외국에증례보고된문헌들을살펴보았다 ( 표 7) (11,25-30). 한국에서보고된종격동기종은모두 9예로서피부근육염환자에서발생하였으며다발근육염에서보고된증례는없었다. 평균나이는 41.3세 ( 범위 18 56세 ) 이고, 1명을제외하고모두여자였다. 모든증례에서간질폐질환이동반되었고, 종격동기종이발생하였을때간질폐질환의악화소견을보였다. 모든환자에서자발종격동기종발생전에스테로이드를사용한병력이있고, 간질폐질환을동반하였던것으로보아종격동기종발생에간질폐질환의악화와스테로이드에의한폐간질의악화효과가모두작용을했을것이라고추정된다. 그러나발생이후에스테로이드증량과함께면역억제제치료, 산소치료를병행하여호전되었고스테로이드및면역억제제에반응이불충분하여간질폐질환이악화된 4명의증례는호흡부전으로사망한것으로보아스테로이드가종격동기종발생에도영향이있으나고용량의스테로이드사용이종격동기종발생후에반드시나쁜예후와관련이 있다고말하기는어렵다. 일반적으로항 Jo-1 항체가양성인경우간질폐질환의빈도가높아간질폐질환과항 Jo-1 항체사이의연관성이있음이밝혀진바있다 (31). 그러나본연구와한국인증례에서간질폐질환동반하고있으나모두항 Jo-1 항체음성이었고, Yoshida 등이고찰한문헌에서도피부근육염 21명의환자중 16명의환자에서간질폐질환을동반하였으나항 Jo-1 항체는음성이었다 (12). 따라서항 Jo-1 항체와자발종격동기종발생은큰연관이없는것으로생각된다. 앞서말했듯이피부혈관병증이발현한피부근육염환자에서자발종격동기종이호발한다고보고되고있는데, 고찰한문헌에서피부혈관병증이동반되었던 3명의증례는모두호전된것으로보아피부혈관병증은자발종격동기종발생후의예후에는큰영향을미치지않는것으로생각된다. Terao 등은피부근육염 / 다발근육염환자에서간질폐질환의정도에따라자발종격동기종을두그룹분류하였는데, 피부혈관병증동반여부와상관없이심한간질폐질환을가진군에서경한간질폐질환이나폐질환이없는군에비해예후가나쁘다고하였다 (19). 즉, 종격동기종에서피부혈관병증동반이종격동기종의발생에영향을미치기는하나예후와는관련이없다고생각된다. 149
대한류마티스학회지제 17 권제 2 호 2010 피부근육염환자에서근육효소 CK의증가는중요한검사소견이고 Fudman 등은 CK 상승이없는경우피부근육염환자의예후가불량하다고하였고 (32), Barvaux 등은 CK가정상이거나상승하더라도미약한경우의환자에서피부근염과연관된간질폐질환을동반하고이때자발종격동기종이발생한경우에는예후가매우불량하다고하였으나 (15), 한국인증례 15명중 12명에서자발종격동기종발생당시 CK 수치는정상범위였고이중 3명은사망을하였다. CK 수치가증가되어있던 3명중에서 1명이사망하여자발종격동기종이발생한환자에서 CK가정상혹은상승이미약하다고하여예후가불량하다고단정적으로말할수는없다. 현재까지기존문헌들에서보고한자발종격동기종의증례는대부분피부근육염이었으며다발근육염에서발생한경우는드물어자발종격동기종의발병은간질폐질환을동반한피부근육염에서호발한다고할수있겠다. 또한일부에서종격동기종이피부근육염 / 다발근육염환자에서나쁜예후를나타내는인자로생각되어왔지만본연구에서고찰한바로는한국인피부근육염 / 다발근육염환자에서종격동기종이발생한경우스테로이드와면역억제제, 산소치료를통해대부분은호전된것으로보아종격동기종이피부근육염 / 다발근육염환자에서사망과관련한나쁜예후인자는아닌것으로생각된다. 본연구는몇가지한계점을가지고있다. 첫째, 161명의환자를후향적으로의무기록을분석한것으로추적관찰에서소실된환자들의예후를평가하지않았다는점이다. 이로인해악성종양, 간질폐질환의발생, 감염등의질환발생이좀더많을수있고, 사망환자수와사망원인질환의비율이달라질수있었다. 둘째, 간질폐질환의분류에있어서조직검사가이루어진경우가없어표준방법인병리학적분류가아닌방사선학적분류를하였기때문에실제와의결과가상이할수있다. 셋째, 검사수치에서다른환자들은피부근육염 / 다발근육염진단당시의 CK/LDH를조사하였으나, 자발종격동기종이발생한환자는종격동기종발생시의검사수치와비교를한한계점이있다. 넷째, 자발종격동기종이발생하였던본원증례에서는이로인해사망한경우가없어자발종격동기종으로사망한환자와그렇지않은환자 에서종격동기종발생후예후에영향을미치는인자에대해통계학적분석을하지못하였다. 마지막으로고찰한문헌들에서추적관찰기간이짧아자발종격동기종호전이후의경과는알수없고, 한국에서보고되지않은자발종격동기종이있을수있어발생빈도는실제로는본연구보다높을수있다. 앞으로호전된자발종격동기종환자들의추후임상경과를평가하여야하며종격동기종이외의다른원인에의해사망한다른피부근육염 / 다발근육염환자들과비교하여예후에미치는영향에대해비교하는것이필요할것으로생각된다. 또한자발종격동기종발생후피부근육염 / 다발근육염의예후에인종간에차이가있는지, 자발종격동기종이발생한다른자가면역질환과비교하여예후에미치는영향에대해연구해보는것도필요할것으로생각된다. 결 결론적으로본연구에서피부근육염 / 다발근육염환자에서자발종격동기종의발생률은흔한합병증은아니었다. 그러나간질폐질환을동반한피부근육염환자에서종격동기종이주로발생하였다. 피부근육염 / 다발근육염환자에서종격동기종이예후에나쁜영향을미치는인자라고단정하기어려우며오히려적절한치료를시행하면좋은예후를보일수도있다고사료된다. 론 참고문헌 1) Dickey BF, Myers AR. Pulmonary disease in polymyositis/dermatomyositis. Semin Arthritis Rheum 1984;14:60-76. 2) Marie I, Hachulla E, Cherin P, Dominique S, Hatron PY, Hellot MF, et al. Interstitial lung disease in polymyositis and dermatomyositis. Arthritis Rheum 2002;47:614-22. 3) Kang EH, Lee EB, Shin KC, Im CH, Chung DH, Han SK, et al. Interstitial lung disease in patients with polymyositis, dermatomyositis and amyopathic dermatomyositis. Rheumatology (Oxford) 2005;44:1282-6. 4) Kim DH, Park JH, Chei CS, Hwang SW, Kim HY, Yoo BH. Spontaneous Pneumomediastinum: clinical investigation. Korean J Thorac Cardiovasc Surg 2006; 150
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