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대한류마티스학회지 Vol. 18, No. 3, September, 2011 http://dx.doi.org/10.4078/jrd.2011.18.3.168 Original Article 교원성질환과동반된간질성폐질환에서류마티스내과협의진료의역할 송명은ㆍ이지수ㆍ노선희 이화여자대학교의학전문대학원류마티스내과 Impact of Rheumatologic Consultations on Detecting Interstitial Lung Disease Associated with Connective Tissue Disease Myung-Eun Song, Jisoo Lee, Sun-Hee Roh Division of Rheumatology, Ewha Womans University School of Medicine, Seoul, Korea Objective. In patients with interstitial lung disease (ILD) associated with connective tissue disease (CTD), chronic ILD related symptoms may often dominate the clinical picture or precede systemic findings and thus often be seen by a non-rheumatologist. The purpose of this study was to evaluate the importance of rheumatologic consultation during ILD work up. Methods. We retrospectively reviewed 64 patients with ILD from a single tertiary center for their clinical and laboratory characteristics, rheumatologic consultation status, and result of the consultation. American College of Rheumatology criteria for classification of each connective tissue disease were utilized. Undifferentiated connective tissue disease () was classified by pre-specified criteria. Results. A total of 23 (36%) of the ILD patients had associated CTD. Five (8%) patients had underlying CTD before the diagnosis of ILD, whereas 18 (28%) patients were diagnosed with CTD after the rheumatologic consultation. ILD patients with CTD were predominantly female, had significantly more frequent radiographic diagnoses of nonspecific interstitial pneumonia, increased frequencies of high titer antinuclear antibody positivity, and rheumatoid factor positivity. Rheumatologic consultation was referred in 36 (56%) patients. In 18 (50%) of the referred patients, CTD was diagnosed. In 61% of the patients diagnosed with CTD as a result of rheumatologic consultation, changes in therapy occurred. Conclusion. A substantial proportion of patients with ILD are found to have an underlying CTD upon evaluation by a rheumatologist. Since ILD associated with CTD mimics idiopathic interstitial pneumonia, rheumatologic consultation may have a significant impact on the clinical care of ILD. Key Words. Interstitial lung disease, Connective tissue diseases, Rheumatologic consultation 서론특발성간질성폐렴 (idiopathic interstitial pneumonias) 은다양한패턴의염증과섬유화에의해폐실질에미만성손상을일으키는원인불명의폐질환을총칭한다 (1). 미만성폐 < 접수일 :2010 년 11 월 15 일, 수정일 (1 차 : 2011 년 1 월 14 일, 2 차 : 2011 년 3 월 4 일 ), 심사통과일 :2011 년 3 월 4 일 > 통신저자 : 이지수서울시양천구안양천로 1071 이화여자대학교의학전문대학원류마티스내과 E-mail:leejisoo@ewha.ac.kr 실질손상은환경적유해물질, 약물, 교원성질환에의해서도유발되며 (2), 이러한 2차성간질성폐질환은특발성간질성폐렴과치료와예후에차이가있기때문에감별진단을요한다 (3). 특발성간질성폐렴은 5년생존율이 20% 미만으로예후가나쁘나, 교원성질환에동반된간질성폐질환은다양한경과를보이며특발성간질성폐렴보다는예후가좋은것은것으로알려져있어 (3), 이두질환의정확한감별진단이치료와예후를결정하는데필수적이다. 그러나, 교원성질환에동반된간질성폐질환은교원성질환의단서가될수있는피부, 혈관, 근골격계, 내부장 168

Rheumatologic Consultations in ILD Associated with CTD 169 기와같은다른기관의침범소견을감지하기어려운경우가많고, 대부분의특발성간질성폐렴과마찬가지로만성적인경과를취하며, 방사선학적소견이나조직검사소견이특발성간질성페렴과유사하여감별이어려운경우가많다 (4,5). 특발성간질성폐렴과유사한임상적증상을보이는교원성질환에는다발성근염 / 피부근염, 전신경화증, 류마티스관절염, 쇼그렌증후군, 복합교원성질환, 미분화교원성질환등이있다 (6). 대부분의교원성질환과동반된간질성폐질환이호흡기증상을주된임상증상으로발현하기때문에류마티스전문의가아닌호흡기전문의에게우선적으로의뢰되는경우가많다. 본연구는 3차병원에간질성폐질환으로내원한환자의증례분석을통해교원성질환과동반된간질성폐질환의진단에있어서류마티스협의진료 ( 협진 ) 의중요성을평가하는데목적이있다. 여러임상분야에걸친종합적진단적접근은간질성폐질환의진단및치료성적을향상시키는데중요한역할을할것이다. 대상및방법대상 2006년 3월 1일부터 2009년 2월 28일까지단일 3차병원에서간질성폐질환을진단받은 64명의환자를대상으로하였다. 방법후향적의무기록검토를통해동반된교원성질환이있는지평가받기위해류마티스내과에협진의뢰여부, 협진결과, 혈액검사, 방사선검사, 폐기능검사, 폐생검검사결과를분석하였다. 협진은호흡기내과와감염내과에서각각 35명, 1명의뢰되었으며, 협진은 2명의류마티스내과의가평가하였다. 류마티스관절염, 전신홍반루푸스, 전신경화증의진단은기준으로는 American College of Rheumatology (ACR) criteria에따라진단하였다 (7-9). 다발성근염 / 피부근염은 Bohan과 Peter가제시한진단기준에따라진단하였다 (10,11). 강직성척추염은 modified New York criteria (12), microscopic polyangiitis는 Chapel Hill consensus conference definition에근거하여진단하였으며 (13), 미분화교원성질환은 Kinder 등이제시한기준에따라레이노현상, 관절통 / 관절염, 광과민성, 의도하지않은체중감소, 조조강직, 구강건조증 / 안구건조증, 연하곤란, 반복적원인불명열, 위식도역류, 피부발진, 구강궤양, 탈모, 근위부근력약화등의교원성질환의증상중한가지를만족하며항핵항체, 류마티스인자, 항SCL70 항체, 항 SS-A/SS-B 항체, 항 Jo-1 항체, 감염의증거없이적혈구침강속도와 C 반응단백증가의검사실소견이양성일때진단하였다 (14). 연속변수의통계비교는 Student T-test를이용하여분석하였으며범주형변수의통계비교는 Chi-square test를이 용하여분석하였다. p<0.05인경우통계적유의성이있는것으로간주하였다. 모든통계의분석은 SPSS version 11.5 를이용하여분석하였다. 결대상환자의임상적특성 총 64명의간질성폐질환환자의평균연령은 66세 ( 범위 30 84세 ) 였으며남자 34명, 여자 30명이었다. 방사선학적으로평가된간질성폐렴의종류는통상적간질성폐렴 (usual interstitial pneumonia) 이 57.8% 으로가장많았으며, 비특이성간질성폐렴 (nonspecific interstitial pneumonia), 특발성기질성폐렴 (cryptogenic organizing pneumonia), 탈락성간질성폐렴 (desquamative interstitial pneumonia), 급성간질성폐렴 (acute interstitial pneumonia) 순이었다. 항핵항체와류마티스인자는 56명의환자에서시행되었으며각각 66.1%, 32.1% 의양성율을보였다. 평균강제폐활량은 73.7% 였으며, 폐확산능은평균 64.2% 였다 ( 표 1). 총 64명의간질성폐질환환자중 36명 (56.3%) 에서류마티스내과의에게협의진료가의뢰되었다 ( 표 1). 류마티스내과로협진의뢰된환자의임상적특성을살펴보면협진이의뢰되지않은환자에비해평균연령과통상적간질성폐렴의빈도가의미있게낮았으며 (p=0.001, p=0.014), 항행항체 1 : 160 이상고역가양성율과류마티스인자의양성율이의미있게높아서 (p=0.026, p=0.008), 젊은연령에서, 방사선학적검사소견상통상적간질성폐렴의양상이아니며, 자가항체가양성일때류마티스내과로협진의뢰되었음을알수있었다 ( 표 2). Table 1. Baseline characteristics of patients with interstitial lung disease Age, years Male, n (%) Radiographic ILD type, n (%) AIP ANA positivity, n (%) RF positivity, n (%) FVC, % DL CO, % Rheumatologic consultation requested n=64 65.6 (12.4) 34 (53) 37 (57.8) 12 (18.8) 12 (18.8) 2 (3.1) 1 (1.6) 37/56 (66.1) 18/56 (32.1) 73.7 (19.2) 64.2 (23.1) 36 (56.3%) Data are presented as mean (SD) except where noted otherwise. ILD: interstitial lung disease, : usual interstitial pneumonia, : nonspecific interstitial pneumonia, : cryptogenic organizing pneumonia, : desquamative interstitial pneumonia, AIP: acute interstitial pneumonia, ANA: antinuclear antibody, RF: rheumatoid factor, FVC: forced vital capacity, DL CO: carbon monoxide diffusion in the lung. 과

170 송명은외 Table 2. Characteristics of interstitial lung disease patients grouped according to their rheumatologic consultation status Not consulted (n=28) Consulted (n=36) p-value Age, years Male, n (%) Radiographic ILD type, n (%) AIP ANA positivity, n (%) 1:40 1:80 1:160 RF positivity, n (%) ESR, mm/hr FVC, % DL CO, % 72.9 (8.8) 17 (60.7) 21 (75) 3 (10.7) 4 (14.3) 0 0 8/20 (40.0) 7/20 (35.0) 1/20 (5.0) 6/20 (30.0) 27.9 (28.3) 71.6 (15.4) 64.5 (23.6) 59.9 (11.8) 17 (47.2) 16 (44.4) 9 (25.0) 8 (22.2) 2 (5.6) 1 (2.8) 19/36 (52.8) 18/36 (50.0) 11/36 (30.6) 24/36 (66.7) 27.2 (24.7) 77.0 (21.4) 64.6 (22.5) 0.001 0.283 0.014 0.146 0.420 0.205 0.374 0.359 0.279 0.026 0.008 0.922 0.312 0.986 Data are presented as mean (SD) except where noted otherwise. ILD: interstitial lung disease, : usual interstitial pneumonia, : nonspecific interstitial pneumonia, : cryptogenic organizing pneumonia, : desquamative interstitial pneumonia, AIP: acute interstitial pneumonia, ANA: antinuclear antibody, RF: rheumatoid factor, ESR: erythrocyte sedimentation rate, FVC: forced vital capacity, DL CO: carbon monoxide diffusion in the lung. Figure 1. Connective tissue disease associations in interstitial lung disease patients studied. *Number (%) of patients. CTD, connective tissue disease, RA: rheumatoid arthritis, SSc: systemic sclerosis, DM: dermatomyositis, SLE: systemic lupus erythematosus, Vas: systemic vasculitis, AS: ankylosing spondylitis, : undifferentiated connective tissue disease. 교원성질환과동반된간질성폐렴환자의임상적특성 간질성폐질환환자의 23명 (36%) 에서교원성질환이동반되었다. 이중 5명 (8%) 은기존에교원성질환을가지고있었으며, 모두류마티스관절염을가지고있었다. 나머지 18명 (28%) 은류마티스내과협진후새롭게교원성질환을진단받았으며, 교원성질환의진단은미분화교원성질환이 5명으로가장많았고, 전신경화증 3명, 피부근염 3명, 류마티스관절염 2명, 전신홍반루푸스 2명, 전신혈관염 2 명, 강직성척추염 1명순이었다 ( 그림 1). 교원성질환과동반된간질성폐질환환자와교원성질환이동반되지않은간질성폐질환환자의임상적특성을분석한결과교원성질환이동반된경우남자의비율이낮았으며 (34.8% 대 63.4%, p=0.028), 방사선학적으로평가된간질성폐렴의종류중비특이성간질성폐렴의빈도가의미있게높았다 (34.8% 대 12.2%, p=0.014). 폐생검빈도는양군간에차이는없었으나, 경기관지폐생검은교원성질환이동반된경우개흉생검에비해더많이시행되었다 (34.8% 대 12.2%, p=0.031). 피부근염에동반된간질성폐렴환자중 1명의환자에서개흉폐생검후기종격동및기흉으로사망하였다. 강제폐활량, 폐확산능, 적혈구침강속도는양군간에차이가없었다. 1:160 이상고역가의항핵항체와류마티스인자의양성율은교원성질환이있는군에서의미있게높았다 ( 표 3). 류마티스내과협진의결과류마티스내과에협진의뢰된환자 36명중 18명 (50%) 에서협진후교원성질환이진단되었다. 교원성질환이진단된 18명의간질성폐질환환자의임상적특성과치료적변화는표 4와같다. 이들환자 18명중 11명 (61%) 에서협의진료후치료적변화가발생하였다. 대부분의환자에서코르티코스테로이드단독또는면역억제제와병용투여로치료약제를전환하였다. 6명의환자에서는고용량스테로이드 ± 싸이클로포스파마이드, 아자티오프린의강력한면역억제치료가투여되었다.

Rheumatologic Consultations in ILD Associated with CTD 171 Table 3. Characteristics of patients with and without connective tissue disease* ILD with CTD (n=23) ILD without CTD (n=41) p Age, years Male, n (%) Radiographic ILD type, n (%) AIP Biopsy, n (%) Transbronchial lung biopsy Open lung biopsy FVC, % DL CO, % ESR, mean±sd, mm/hr ANA positivity, n (%) 1:40 1:80 1:160 RF positivity, n (%) 62.3 (11.6) 10 (43.5) 4 (17.4) 1 (4.3) 0 12 (52.2) 4 (17.4) 69.9 (24.6) 60.1 (25.6) 28.2 (26.4) 18/23 (78.3) 10 (43.5) 12/23 (52.2) 67.4 (12.6) 26 (63.4) 27 (65.9) 4 (9.8) 8 (19.5) 1 (2.4) 1 (2.4) 13 (31.7) 5 (12.2) 8 (19.5) 75.4 (16.5) 65.9 (22.1) 27.1 (26.2) 19/33 (57.5) 15 (45.5) 4 (12.1) 7/33 (21.2) 0.109 0.028 0.082 0.014 0.835 0.674 0.450 0.107 0.031 0.835 0.371 0.431 0.882 0.108 0.884 0.042 0.016 Data are presented as mean (SD) except where noted otherwise. ILD: interstitial lung disease, : usual interstitial pneumonia, : nonspecific interstitial pneumonia, : cryptogenic organizing pneumonia, : desquamative interstitial pneumonia, AIP: acute interstitial pneumonia, ANA: antinuclear antibody, RF: rheumatoid factor, ESR: erythrocyte sedimentation rate, FVC: forced vital capacity DL CO: carbon monoxide diffusion in the lung. Table 4. Changes in therapy in interstitial lung disease patients diagnosed with connective disease after rheumatologic consultation Patient Post-consultation diagnosis Serology Imaging pattern Changes in treatment 73 F 69 M 74 M 68 F 59 F 71 M 61 F 73 F 61 F 61 M 55 F 47 F 61 M 54 F 61 M 38 F 74 F 35 M SSc DM SSc RA RA Vas RA SLE SLE DM AS Vas DM +ANA, +SSA +ANA +ANA, +RF, +LA +ANA +SSB +ANA, +RF, +SSA, +ANCA, +CCP +RF, +ANCA +ANA, +ANCA +ANA, +ANCA +RF, +ANCA +ANA, +ANCA +ANA, +RF, +SSA +ANA, +DNA +SSA +ANA, +SSA +ANA, +SSA +ANA +ANA +ANA, +RF Negative CS, MTX High CS CS, AZT High CS High CS, CY HCQ, SSZ CS, HCQ, AZT CS, HCQ, AZT High CS High CS, CY High CS, AZT RA: rheumatoid arthritis, SSc: systemic sclerosis, DM: dermatomyositis, SLE: systemic lupus erythematosus, Vas: systemic vasculitis, AS: ankylosing spondylitis, : undifferentiated connective tissue disease, : usual interstitial pneumonia, : cryptogenic organizing pneumonia, : desquamative interstitial pneumonia, ANA: antinuclear antibody, SSA: anti-ssa, RF: rheumatoid factor, LA: lupus anticoagulant, SSB: anti-ssb, ANCA: antineutrophilic cytoplasmic antibody, CCP: anti-cyclic citrullinated peptide, DNA: anti-double strand DNA, : nonspecific interstitial pneumonia, CS: corticosteroid, High CS: 1 mg/kg/d corticosteroid, CY: cyclophosphamide, MTX: methotrexate, HCQ: hydroxychloroquine, SSZ: sulfasalazine, AZT: azathioprine.

172 송명은외 고찰본연구의결과간질성폐질환환자의 36% 에서교원성질환이동반되었으며, 28% 의환자에서류마티스내과협진후교원성질환이진단되어간질성폐질환의평가에서류마티스내과협의진료가중요한역할을담당하는것을알수있었다. 이는최근호흡기내과전문의와류마티스내과전문의로구성된간질성폐질환클리닉의코호트연구결과 50% 의환자에서동반된교원성질환이진단되어류마티스내과협진의중요성을강조한논문의결과를뒷받침하는소견이다 (15). 이전의역학연구에서는교원성질환과동반된간질성폐질환의유병률이 12.4% (16), 10% (17) 로낮게보고되었다. 이런역학연구와본연구의유병율의차이는 3차병원으로의진료의뢰하는진료양상의차이때문에발생할수도있지만간질성폐렴의평가과정중류마티스내과협의진료빈도의차이에의해서도발생할수있다. 본연구에서는전체환자의 56.3% 에서류마티스내과로협진의뢰되었으며이중 50% 의환자에서교원성질환이확진되었다. 대부분의간질성폐질환의역학연구는호흡기전문의를중심으로한코호트연구로동반된교원성질환의증상이미약하여감지하기어려운경우진단이누락되는경우가발생하여교원성질환의유병률이실제보다낮게측정될수있다. 플랑드르인을대상으로한간질성폐질환의역학연구에서는간질성폐질환과동반된교원성질환의원인으로류마티스관절염이 54% 로가장많았는데 (17), 이는증상을감지하기어려운전신교원성질환보다비교적관절증상이명확한류마티스관절염환자가많이진단되어전신교원성질환의진단적평가가충분하지않았음을간접적으로시사한다. 본연구에서협진후진단된교원성질환의진단명중류마티스관절염은 2명 (11%), 미분화교원성질환을포함하는다른전신교원성질환의빈도가 89% 로대부분을차지하여진단이어렵거나증상이미약한교원성질환의진단율이상대적으로상승한것을알수있었다. 이는호흡기내과전문의와류마티스내과전문의가동시에진료를하는간질성폐질환특수클리닉의코호트연구에서도관찰되는현상으로류마티스관절염은 20% 의환자에서진단된반면류마티스관절염을제외한다른교원성질환은 80% 의경우진단되어간질성폐질환의평가에있어서류마티스협의진료의중요성을시사하는소견이다 (15). 교원성질환이동반간질성폐질환의경우특발성간질성폐렴과증상이매우유사하여감별진단이어려운경우가많다. 만성간질성폐질환이주된증상으로나타날수있는교원성질환에는다발성근염 / 피부근염, 전신경화증, 류마티스관절염, 쇼그렌증후군, 복합교원성질환, 미분화교원성질환등이있다 (6). 만성간질성폐질환을보이는환자의 15 20% 에서숨겨진교원성질환을가지고있거나, 시간이지나면서교원성질환이발현하는것으로추정되고있다 (18). 교원성질환에동반된간질성폐질환을뒷 받침하는소견으로는자가항체의출현을들수있다. 본연구에서는류마티스인자, 고역가항핵항체를포함하는자가항체의양성율이교원성질환이동반되지않은군에비해의미있게높았다. Fischer 등의보고에따르면특발성폐섬유화증으로진단된환자에서전신경화증특이항체인항Scl70 항체와항핵항체 ( 핵인염색패턴 ) 를측정한결과 9% 이하의환자에서전신경화증특이항체가검출되었고전신경화증으로진단되었다 (19). 교원성질환동반간질성폐질환의진단을뒷받침하는방사선학적소견으로는늑막삼출액이나늑막비후소견이있는경우가보고되었고 (20), 조직학적유형으로는비특이성간질성폐렴이있는경우가능성을높이는소견으로보고되었다 (21-23). 그이외에도조직학적으로여포성세기관지염, 림프구성형질세포의침윤이있는경우동반된교원성질환을의심해볼수있는소견이다 (21). 비특이성간질성폐렴은교원성질환과동반된간질성폐질환의경우가장흔한조직학적유형으로본연구에서도비특이성간질성폐렴이교원성질환과동반된환자에서동반되지않은환자에서보다유의하게더많이관찰되었다. 여성에서자가항체가양성이며방사선학적으로비특이성간질성폐렴의양상을보이는간질성폐렴환자의경우동반된교원성질환의평가를위해류마티스내과협진을의뢰하는것이권장되는소견이다. 교원성질환에동반된간질성폐질환을특발성간질성폐렴과반드시감별진단해야하는이유는첫째, 전신질환과관련된기관침범의범위를평가하고적절한치료약제를선정하는데도움이되기때문이다 (24,25). 본연구의결과류마티스내과협의진료후교원성질환이진단된간질성폐질환환자의약 60% 에서치료적변화가발생하였으며약 1/3의환자에서는싸이글로포스파마이드와고용량코르티코스테로이드를포함하는강력한면역억제치료가투여되었다. 간질성폐질환특수클리닉의코호트연구에서도교원성질환이진단된 80% 의환자에서치료약제의변화가있었다 (15). 이런면역억제치료의신속하고적절한투여는전신교원성질환으로인해발생할수있는기관침범의범위를최소화시킬수있다. 둘째, 교원성질환과동반된폐질환은대부분임상증상, 방사선학적검사, 특이자가항체검사로진단이가능하여합병증을유발할수있는개흉폐생검과같은침습적검사를피할수있다. Utz 등이특발성폐섬유화증환자에서폐생검후 21.7% 의높은사망률을보고하여개흉폐생검의위험성이제기되었으며 (26), 우리나라환자를대상으로한연구에서도특발성페섬유화증환자의진단을위해개흉폐생검을시행했던 200예의조사결과시술 30일이후사망율은 4.3% 로보고되었고, 특히특발성페섬유화증이급성악화기에는 28.6% 의사망률을보여개흉폐생검의위험성이보고되었다 (27). 피부근염 / 다발성근염의경우자발적기흉과기종격동이발생할수있는질환으로폐생검으로인

Rheumatologic Consultations in ILD Associated with CTD 173 한합병증발생이증가할수있다 (28). 본연구에서도피부근염에동반된간질성폐질환환자 1명의환자에서개흉폐생검후기종격동및기흉으로사망하였다. 마지막으로동반된교원성질환은예후를결정하는중요인자로서교원성질환동반간질성폐질환의경우특발성폐섬유화증보다생존율이좋은것으로보고되었다. 이연구는단일기관에서후향적의무기록조사를통해수집된자료를분석한연구라는것제한점을가지고있다. 그러나간질성폐질환환자에서동반된교원성질환을평가하는것인환자의치료방법과예후를결정하는데매우중요하며이런과정에서류마티스내과협의진료가중요한역할을담당한다는것을제시한연구의의의를지니고있다. 결론간질성폐질환환자의약 36% 에서교원성질환이동반되었고, 28% 의환자에서류마티스내과협진후교원성질환이진단되었다. 교원성질환특이자가항체의검출과방사선학적검사상비특이성간질성폐렴의소견은동반된교원성질환을의심해볼수있는소견이다. 류마티스내과협진후교원성질환이진단된간질성폐질환환자의상당수에서면역억제제를포함하는치료적변화가발생하였다. 간질성폐질환환자의평가에있어서류마티스내과협의진료는동반된교원성질환을진단하고치료방법을결정하는데중요한역할을하는것으로생각된다. 참고문헌 1. Ellis SM, Hansell DM. Idiopathic interstitial pneumonias: imaging-pathology correlation. Eur Radiol 2002;12: 610-26. 2. Raghu G, Brown KK. Interstitial lung disease: clinical evaluation and keys to an accurate diagnosis. Clin Chest Med 2004;25:409-19. 3.Park JH, Kim DS, Park IN, Jang SJ, Kitaichi M, Nicholson AG, et al. Prognosis of fibrotic interstitial pneumonia: idiopathic versus collagen vascular diseaserelated subtypes. Am J Respir Crit Care Med 2007; 175:705-11. 4. Reynolds HY. Diagnostic and management strategies for diffuse interstitial lung disease. Chest 1998;113:192-202. 5. Flaherty KR, Andrei AC, King TE Jr, Raghu G, Colby TV, Wells A, et al. Idiopathic interstitial pneumonia: do community and academic physicians agree on diagnosis? Am J Respir Crit Care Med 2007;175:1054-60. 6. Tzelepis GE, Toya SP, Moutsopoulos HM. Occult connective tissue diseases mimicking idiopathic interstitial pneumonias. Eur Respir J 2008;31:11-20. 7. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24. 8. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-7. 9. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum 1980;23:581-90. 10. Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med 1975;292:403-7. 11. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med 1975;292:344-7. 12. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361-8. 13. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994;37:187-92. 14. Kinder BW, Collard HR, Koth L, Daikh DI, Wolters PJ, Elicker B, et al. Idiopathic nonspecific interstitial pneumonia: lung manifestation of undifferentiated connective tissue disease? Am J Respir Crit Care Med 2007;176: 691-7. 15. Castelino FV, Goldberg H, Dellaripa PF. The impact of rheumatological evaluation in the management of patients with interstitial lung disease. Rheumatology (Oxford) 2011;50:489-93. 16. Karakatsani A, Papakosta D, Rapti A, Antoniou KM, Dimadi M, Markopoulou A, et al; Hellenic Interstitial Lung Diseases Group. Epidemiology of interstitial lung diseases in Greece. Respir Med 2009;103:1122-9. 17. Roelandt M, Demedts M, Callebaut W, Coolen D, Slabbynck H, Bockaert J, et al. Epidemiology of interstitial lung disease (ILD) in flanders: registration by pneumologists in 1992-1994. Working group on ILD, VRGT. Vereniging voor Respiratoire Gezondheidszorg en Tuberculosebestrijding. Acta Clin Belg 1995;50:260-8. 18. Strange C, Highland KB. Interstitial lung disease in the patient who has connective tissue disease. Clin Chest Med 2004;25:549-59. 19. Fischer A, Pfalzgraf FJ, Feghali-Bostwick CA, Wright TM, Curran-Everett D, West SG, et al. Anti-th/to-positivity in a cohort of patients with idiopathic pulmonary fibrosis. J Rheumatol 2006;33:1600-5. 20. Highland KB, Heffner JE. Pleural effusion in interstitial lung disease. Curr Opin Pulm Med 2004;10:390-6. 21. Tansey D, Wells AU, Colby TV, Ip S, Nikolakoupolou A, du Bois RM, et al. Variations in histological patterns of interstitial pneumonia between connective tissue disorders and their relationship to prognosis. Histopathology 2004;44:585-96. 22. Fujita J, Ohtsuki Y, Yoshinouchi T, Yamadori I, Bandoh S, Tokuda M, et al. Idiopathic non-specific interstitial pneumonia: as an "autoimmune interstitial pneumonia".

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