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1 Journal of Rheumatic Diseases Vol. 20, No. 4, August Review Article 류마티스질환의피부소견 이은소 아주대학교의과대학피부과학교실 Skin and Rheumatic Disease Eun-So Lee Department of Dermatology, Ajou University School of Medicine, Suwon, Korea Many rheumatic diseases may involve any organ system of the body including the skin. Proper understanding of rheumatic skin disease is necessary for making a diagnosis. In addition, there are important relationships existing between the cutaneous and systemic manifestations of rheumatic diseases. In management of these diseases, the interdisciplinary approach could generate better results. Among rheumatic diseases, the cutaneous manifestations of three major rheumatic diseases such as lupus erythematosus (LE), dermatomyositis (DM)/polymyositis and scleroderma/systemic sclerosis (SSc) will all be reviewed. Key Words. Rheumatic disease, Skin manifestsions, Lupus erythematosus, Dermatomyositis, Scleroderma 류마티스병 (rheumatic disease) 은의학주제표제 (MeSH) 에서 1990년에도입한용어로 결합조직, 특히관절과연관구조에발생하는질환으로염증, 변성또는대사장애를특징으로한다 (Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement) 라고정의하고있다. MeSH 분류에의하면류마티스병은근골격질환, 피부와결합조직병의하위분류로류마티스관절염, 섬유근육통통풍, Sternocostoclavicular Hyperostosis, 골관절염, Polymyalgia Rheumatica, 류마티스열등이속하나이글에서는결합조직병에속하는대표적인질환인홍반루푸스 (lupus erythematosus), 피부근염 (dermatomyositis) 과피부경화증 (scleroderma) 의피부소견에대해설명하고자한다. 이들질환의피부소견은전신소견과밀접한연관이있고진단에내릴때매우중요한단서가되므로, 피부증상을정확 하게파악하는것이올바른진단과이에따른적절한치료의첫걸음이될수있기때문이다. 홍반루푸스 (Lupus Erythematosus, LE) 홍반루푸스에서피부는두번째로많이병발하는기관으로매우다양하게나타난다 (1). 홍반루푸스의피부소견은 1981 년 Gilliam이제안한분류에의하면특징적인조직소견을보이는홍반루푸스특이피부병 (LE-specific skin disease) 과조직학적으로특징적인소견을보이지않아다른질환에서도볼수있는홍반루푸스비특이피부병 (LE-nonspecific skin disease) 으로나눌수있다 (Table 1) (2,3). 홍반루푸스특이 라함은경계면피부염 (interface dermatitis) 의양상을보이는병변을일컬으며, 피부홍반루프스는대부분홍반루푸스특이피부병과동의어로사용된다. 홍반루푸스특이피부소견은병변의형태나지속경 <Received:June 15, 2013, Revised:July 27, 2013, Accepted:July 29, 2013> Corresponding to:eun-so Lee, Department of Dermatology, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon , Korea. esl@ajou.ac.kr pissn: X, eissn: Copyright c 2013 by The Korean College of Rheumatology This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited. 209

2 210 이은소 Table 1. The modified Gilliam classification of skin lesions associated with LE (3) LE-specific skin disease (Cutaneous LE, CLE) LE-nonspecific skin disease A. Acute cutaneous LE (ACLE) 1. Localized ACLE (malar rash; butterfly rash) 2. Generalized ACLE (lupus maculopapular lupus rash, SLE rash, rash, photosensitive lupus dermatitis) B. Subacute cutaneous LE (SCLE) 1. Annular SCLE (syn. lupus marginatus, symmetric erythema centrifugum, autoimmune annular erythema, lupus erythematosus gyratus repens) 2. Papulosquamous SCLE (syn. disseminated DLE, subacute disseminated LE, superficial disseminated LE, psoriasiform LE, pityriasiform LE, and maculopapular photosensitive LE) C. Chronic cutaneous LE (CCLE) 1. Classic discoid LE (DLE) 2. Localized DLE 3. Generalized DLE 4. Hypertrophic/verrucous DLE 5. Lupus profundus/lupus panniculitis 6. Mucosal DLE 7. Oral DLE 8. Conjunctival DLE 9. Lupus tumidus (urticarial plaque of LE) 10. Chilblain LE (chilblain lupus) 11. Lichenoid DLE (LE/lichen planus overlap, lupus planus) A. Cutaneous vascular disease 1. Vasculitis a. Leukocytoclastic (1) Palpable purpura (2) Urticarial vasculitis b. Periarteritis nodosa-like cutaneous lesions 2. Vasculopathy a. Degos disease-like lesions b. Secondary atrophie blanche (syn. livedoid vasculitis, livedo vasculitis) 3. Periungual telangiectasia 4. Livedo reticularis 5. Thrombophlebitis 6. Raynaud phenomenon 7. Erythromelalgia (erythermalgia) B. Nonscarring alopecia 1. "Lupus hair" 2. Telogen effluvium 3. Alopecia areata C. Sclerodactyly D. Rheumatoid nodules E. Calcinosis cutis F. LE-nonspecific bullous lesions G. Urticaria H. Papulonodular mucinosis I. Cutis laxa/anetoderma J. Acanthosis nigricans (type B insulin resistance) K. Erythema multiforme L. Leg ulcers M. Lichen planus 과, 동반한전신증상의정도, 특성에따라급성피부홍반루푸스 (acute cutaneous LE, ACLE), 아급성피부홍반루푸스 (subacute cutaneous LE, SCLE), 그리고만성피부홍반루푸스 (chronic cutaneous LE, discoid LE, CCLE, DLE) 의 3가지로나뉘어진다. 뺨의홍반 (malar rash) 을보이는급성피부홍반루푸스는전체홍반루푸스환자의 20 60% 에서볼수있으며, 전신홍반루푸스와마찬가지로여성에서남성에비해흔하게나타나고 (8:1) 모든인종에서볼수있다 (4). 아급성피부홍반루푸스는전체홍반루푸스환자의 7 27% 에서볼수있는데 1차적으로백인여성에서많이볼수있다. 만성피부홍반루푸스의가장흔한형태인원반모양홍반루푸스 (discoid LE) 는전신홍반루푸스환자의 15 30% 에서나타난다고알려져있으나피부에만홍반루푸스가있는경우까지포함하면 2, 3배더많을것으로추측하고있다 (5). 원반모양홍반루푸스는여성이남성에비하면많이이환되나전신홍반루푸스에비하면그정도는낮고 (3:1 2), 모든인종에서볼수있다. 만성피부홍반루푸스 (Chronic cutaneous LE, CCLE) CCLE의대표적인병변은원반모양홍반 (discoid erythema) 으로목위쪽의햇빛노출부위에국한해서생기는것이보통이다. 병변은경계가비교적분명한홍반으로표면에약간의인설을가지며때로는모공이확장되고각전이박힌모습 (carpet tack sign) 도보인다. 호전과악화를거듭하면서수개월또는수년경과된후염증의소실과함께대개의경우에서위축반흔, 색소탈실 / 침착또는모세혈관확장등을남기며치유되므로두피에병변이있으면반흔성탈모를보인다. 얼굴에생기는 DLE는대개코, 입술주름 (nasolabial fold) 에는생기지않으나뺨에생기는 DLE는급성홍반루푸스와감별이힘들다. 범발성 (generalized) DLE는 SLE와더흔히연관이되어목부위이상, 이하에서모두발생한다. 국내에서는 CCLE의임상적고찰을통하여국소형 DLE가전체환자의 %, 범발형 DLE 가 % 를차지하며, 국소형의경우에는얼굴, 범발형의경우에는몸통과상지가흔한발생부위임을보고한바있다 (6,7). DLE 환자의 60% 에서두피에병변이발생하여 1/3의환자는이로인한비가역적인반흔성탈모를갖게된다. 이러한탈모는전신홍반루푸스에볼수있는가역적인비반흔성탈모과구별되어야한다.

3 류마티스질환의피부소견 211 CCLE는비교적임상경과가양호하나, 환자의 5 6.6% 에서 SLE로진행될수있다 (8). 국내연구에서는 CCLE중범발형 DLE에서다소높은전환경향을보였다 (6). SLE 환자에서 10 20% 는발병당시또는경과중에 DLE의피부병변을가질수있는데이런경우에는그렇지않은환자보다는예후가비교적양호한것으로알려져있다 (4). DLE의변형으로동창루푸스 (chilblain lupus), 비후루푸스 (hypertrophic lupus), 심부홍반루푸스 (lupus profundus, lupus panniculitis), 비대루푸스 (lupus erythematosus tumidus) 등이있다. 아급성피부홍반루푸스 (Subacute cutaneous LE, SCLE) 어느정도의전신증상을가지는홍반루푸스환자에서볼수있는재발성피부병변으로구진인설성홍반 (Papulosquamous/psoriasiform) 또는환상홍반 (Annular SCLE) 등으로나타나며, 드물게는두가지병변이함께발생하기도한다. 특징적으로광선노출부위에대칭적으로발생하므로목의 V자부위, 흉부의윗부분, 등, 어깨, 팔과손의신측부 (extensor aspects) 부위에발생한다. 병변은반흔을남기지않고치유되며염증후색소이상 ( 흔하게백반증유사저색소증 ) 과모세혈관확장증이지속되기도한다 (9). SCLE는최근다양한약물에의해발생한증례가많이보고되고있으며, 이약물들은태선모양또는광과민성약물반응을유발할수있다 (10). 약물유발 SCLE는특징적인광노출부위의병변과 Ro/SS-A 항체양성소견을보이며피부외의증상은드물다. SCLE는중년의백인여성에게호발하는것으로알려져있고 LE 환자의 7 27% 에서발생한다고하는데, 한국인에서는상반된연구결과가있다. 구미백인에비해한국인에서 SCLE의발생빈도가훨씬낮으며, 고리모양병변은없거나드물고대부분구진또는구진인설성홍반의형태라고한보고와 (11), 117명의한국인 LE 환자를대상으로다른연구에서는 11명 (9%) 으로구미에서의연구와비슷한유병률을보였고, 고리모양병변이더많았다는보고가있었다 (12). SCLE 환자의거의반수에서 ARA의 SLE 진단기준에 4가지를만족하나, 대부분의환자에서전신증상은심하지않고, 신장, 중추신경계침범은각 0 21%, 0 19% 로흔하지않다. 구진인설성 SCLE, 백혈구감소증, ANA 1:640 이상의고역가, anti-dsdna 항체양성은 SLE 로발전하는위험인자로간주되고있다 SCLE는다른자가면역질환인 Sjgren's syndrome, 류마티스관절염, 하시모토갑상샘염이동반되기도한다 (9). 운인설을가진다. 병변은비교적급속히발생하며, 산재된홍반으로시작하여융합될수도있다. 대개경계가불분명하고소양감도거의느끼지않으며, 이마, 턱, 목의 V 부위에도생기나, 코, 입술주름은침범하지않아피부근염과감별이된다. 이런병변의분포는광과민성과밀접한연관이있기때문이다. 전신형은광범위한홍역상홍반 (morbiliform erythema) 으로대부분광선노출부위와팔과손의신측부에나타나나특징적으로수지관절배부 (knuckles) 를침범하지않으므로피부근염의피부병변과감별이가능하다. 다른루푸스비특이피부병변은 ACLE가활발히진행될때동반된다 (13). 독성표피괴사용해 (toxic epidermal necrolysis, TEN) 와같은증상이매우드물지만나타나기도한다. ACLE 는대개반흔을남기지않고자연치유된다. 환자들은한가지이상의피부병변을가지는경우가많아한연구에의하면 CLE환자중 68% 는한가지, 29% 는 2가지, 3% 는 3가지의질환특이피부병변을지니는것으로나타났다 (14). 질환비특이피부증상많은피부증상이루푸스에비특이적으로나타나며, 루푸스특이피부병변과조직소견이다르다. 이런병변은 SLE 환자에서볼수있기도하고나중에루푸스가발생할수있는위험도를지닌다. 이런병변으로는혈관염, 광과민반응, 탈모, 레이노현상, 망상청피반, 연부조직석회화, 물집병변, 두드러기, 피부점액증 (cutaneous mucinosis), 피부괴사, 궤양, 조갑변화등이있다. 이런병변은 SLE 환자에서질병활성도의척도가되는데, 나쁜예후를보이는피부병변에속하는것은광과민성, 구강궤양, 레이노현상, 비반흔성탈모이다 (15). 피부혈관계병변은혈관염, 조갑주위의모세혈관확장, 레이노현상, 청피반양혈관염등으로나타난다. 혈관염은작은혈관의백혈구파쇄성혈관염으로가장특징적으로나타나며만져지는자반이나두드러기성혈관염의양상을보인다. SLE 환자의 10 20% 에서혈관염을볼수있다. 두드러기성혈관염은저보체증과연관이있고통증이있는두드러기가 24시간이상지속하며자반또는색소침착이남는것이특징이다. 망상청피반양상의혈관병변은 SLE 환자의 10% 에서볼수있는데 antiphospholipid antibodies 존재와연관이있다. SLE에서가장흔한비특이병변으로비반흔성탈모가환자의 40 70% 에서오는데이의원인으로두피의전두부에서모발이짧게부서진 lupus hair, 휴지기탈모, 원형탈모증등이있다 (14). 급성피부홍반성루푸스 (Acute cutaneous LE, ACLE) ACLE는국소형과전신형으로나눌수있다. 대표적인국소형은뺨의홍반 (malar or butterfly rash) 인데 SLE 환자의 50% 이하에서볼수있다 (9). 뺨의홍반 (malar rash) 은나비모양의코상부를포함한대칭성발진으로서약간의부종과가벼 전신증상과피부증상과의관계 SLE의위험도는 ACLE가가장높고 CCLE가가장낮으며 SCLE는중간이다. 홍반루푸스특이피부병을보이는 191 명의환자를대상으로한연구에서 ACLE의 72%, SCLE의 58%, CCLE의가장흔한형태인 DLE의 28%, 그리고두경

4 212 이은소 부에국한된 DLE의 6% 에서 SLE가동반되었다 (16). SLE 환자에서나타난피부증상을보면 CCLE는 15 20%, SCLE는 10 15%, ACLE는 30 50% 이었으며, 루푸스비특이증상을포함하면 72 85% 의 SLE환자가피부병변을가지고있고이중 23 28% 는피부증상이초기증상이었다 (17). 피부병변에따라전신증상을동반할가능성을예측할수있는데국소형 DLE, hypertrophic LE, LE panniculitis, LE tumidus의경우피부질환만가질가능성이많고, 전신성 DLE나 SCLE, ACLE, 질환비특이피부증상이있으면전신질환을동반할가능성이많다. 진단기준전신홍반루푸스의미국류마티스학회에서제시한진단기준에는 11개항목중 4개가피부소견으로매우중요한기준이된다 (18,19). 따라서피부증상네가지기준만으로도진단기준을만족하게된다 (20). 또한피부병변중에는광과민성과 malar rash, DLE와구강궤양은서로중복되는병변이고조직검사를하지않으면 malar rash나원반모양루푸스는진단이어렵고, 구강궤양이홍반루푸스에특이성이없다는점, 최근의피부루푸스의분류는매우복잡하며, 피부근염과같은다른자가면역질환의환자도진단기준을일부만족하므로진단이잘못될가능성이많다 (17). 따라서이를보충하기위하여 Systemic Lupus International Collaborating Clinics (SLICC) group에서전신홍반루푸스의새로운분류기준을발표하였다 (Table 2) (21). 이기준은피부증상에서 malar rash와광과민성을나누지않고아급성홍반루푸스를포함한급성홍반루푸스의증상으로하고, 만성홍반루푸스의증상을포함하였고구강궤양과더불어비반흔성탈모를독립적인기준으로설정하였다. 병리조직학적소견 LE의특이피부질환에서의조직소견은과각화증, 표피위축, 기저세포의액화변성, 기저막대의피부, 진피의부종, 표피-진피경계부와진피의혈관주위및피부부속기주위의단핵구침윤이다 (4). ACLE는 SCLE와 CCLE에비해조직변화가덜뚜렷해서침윤된세포가많지않은경계면피부염의소견을보인다. SCLE도흔하게경계면피부염의소견을보이며 CCLE보다는정도가경하다. 이외에도루푸스지방층염은특징적인 LE의표피, 진피변화가없기때문에진단이어렵다. 루푸스특이피부병에서는면역조직검사가진단에도움이된다. 병변과비병변부위의표피-진피경계부에 IgG, IgA, IgM과보체성분들 (C3, C4, Clq, properdin, factor B, the membrane attack complex C5b-C9) 이연속적인과립형태나띠모양으로침착되어있음을형광으로볼수있다. 광선에노출되지않은정상피부에서 3가지이상의성분이양성으로나오면 SLE의진단적가치가높으며루푸스신장 염으로진행될위험성이높다 (4). 치료 자외선을피하는것이치료와예방에중요하므로 UVA와 UVB를효과적으로차단할수있는자외선차단제의사용을강조하여야한다. 스테로이드연고나병변내주입도효과적이며최근에는 tacrolimus 국소제도스테로이드제와동등한효과가있음이증명되었다 (22). 국소치료에반응하지않는 CLE 환자의약 75% 는한가지또는그이상의항말라리아제 (hydroxychloroquine 또는 chloroquine) 를사용한다. 치료전에안과검사가필수적이며, 치료중 6 12개월간격으로계속안과검사를시행해야한다. 항말라리아제에반응을보이지않는경우 diaminodiphenylsulfone (dapsone) 을사용할수있고, isotretinoin, acitretin 등도사용한다. 불응성 CLE에 thalidomide 가효과적이나말초신경염에유의하여야한다 (22). 피부에만병변이국한된경우가능한한전신적으로스테로이드를사용하지않는것이좋으나, 매우심한경우사용할수있다. 그러나장기사용에따른부작용에유의하여야한다. 이외다른면역억제제인 azathioprine, mycophenolate mofetil, methotrexate, leflunomide, cyclosporine 등도사용하였다는보고가있고, 최근생물학적제제인 TNFα 억제제 (etanercept, adalimumab, infliximab), rituximab, IFN-alpha에대한단일클론항체등이사용되고있거나현재연구중이다 (4). 피부근염 (Dermatomyositis, DM) 피부근염은피부와근육을주로침범하는질환으로피부의부종, 홍반, 모세혈관확장, 색소침착, 간질석회화등이나타나며여러근육의염증성근염으로근허약을보이는것이특징이다. 피부근염은다양한임상양상을보여피부에만침범하거나 (amyopathic DM, dermatomyositis sine myositis), 근육의변화가미약하여임상적인증상은보이지않으면서검사결과에만이상이있는경우 (hypomyopathic DM), 피부에는염증이없으면서근육에만염증이있는경우 (polymyositis, PM) 등이있다 (23). 전형적인피부근염환자의 60% 에서는피부병변과근육허약이동시에나타나나, 30% 에서는근육침범이전에피부증상이먼저나타난다. 반면 10% 의환자는피부증상보다근육허약을먼저경험한다 (24). 피부증상정도는근육증상과발생시기, 활성도, 치료반응과비례하지않는다. 피부증상은대개피부의가려움증또는작열감으로시작하고광과민성이특징적이다. 특징적인염증성피부병변 일차적인피부증상은매우특징적으로가려움증을동반한대칭적인연자색홍반이여러부위에나타난다. 손가락, 손, 아래팔등의신측부 (extensor aspect); 팔, 어깨세모

5 류마티스질환의피부소견 213 Table 2. Clinical and immunologic criteria used in the SLICC classification system (21) Clinical criteria 1. Acute cutaneous lupus, including: Lupus malar rash (do not count if malar discoid) Bullous lupus Toxic epidermal necrolysis variant of SLE Maculopapular lupus rash Photosensitive lupus rash in the absence of dermatomyositis OR subacute cutaneous lupus (nonindurated psoriaform and/or annular polycyclic lesions that resolve without scarring, although occasionally with postinflammatory dyspigmentation or telangiectasias) 2. Chronic cutaneous lupus, including: Classic discoid rash Localized (above the neck) Generalized (above and below the neck) Hypertrophic (verrucous) lupus Lupus panniculitis (profundus) Mucosal lupus Lupus erythematosus tumidus Chillblains lupus Discoid lupus/lichen planus overlap 3. Oral ulcers Palate Buccal Tongue OR nasal ulcers in the absence of other causes, such as vasculitis, Behçet s disease, infection (herpesvirus), inflammatory bowel disease, reactive arthritis, and acidic foods 4. Nonscarring alopecia (diffuse thinning or hair fragility with visible broken hairs) in the absence of other causes such as alopecia areata, drugs, iron deficiency, and androgenic alopecia 5. Synovitis involving 2 or more joints, characterized by swelling or effusion OR tenderness in 2 or more joints and at least 30 minutes of morning stiffness 6. Serositis Typical pleurisy for more than 1 day OR pleural effusions OR pleural rub Typical pericardial pain (pain with recumbency improved by sitting forward) for more than 1 day OR pericardial effusion OR pericardial rub OR pericarditis by electrocardiography in the absence of other causes, such as infection, uremia, and Dressler s pericarditis 7. Renal Urine protein to-creatinine ratio (or 24-hour urine protein) representing 500 mg protein/24 hours OR red blood cell casts 8. Neurologic Seizures Psychosis Mononeuritis multiplex in the absence of other known causes such as primary vasculitis Myelitis Peripheral or cranial neuropathy in the absence of other known causes such as primary vasculitis, infection, and diabetes mellitus Acute confusional state in the absence of other causes, including toxic/metabolic, uremia, drugs 9. Hemolytic anemia 10. Leukopenia (4,000/mm 3 at least once) in the absence of other known causes such as Felty s syndrome, drugs, and portal hypertension OR Lymphopenia (1,000/mm 3 at least once) in the absence of other known causes such as corticosteroids, drugs, and infection

6 214 이은소 Table 2. Continued 11. Thrombocytopenia (100,000/mm 3 ) at least once in the absence of other known causes such as drugs, portal hypertension, and thrombotic thrombocytopenic purpura Immunologic criteria 1. ANA level above laboratory reference range 2. Anti-dsDNA antibody level above laboratory reference range (or 2-fold the reference range if tested by ELISA) 3. Anti-Sm: presence of antibody to Sm nuclear antigen 4. Antiphospholipid antibody positivity as determined by any of the following: Positive test result for lupus anticoagulant False-positive test result for rapid plasma reagin Medium- or high-titer anticardiolipin antibody level (IgA, IgG, or IgM) Positive test result for anti 2-glycoprotein I (IgA, IgG, or IgM) 5. Low complement Low C3 Low C4 Low CH50 6. Direct Coombs test in the absence of hemolytic anemia Criteria are cumulative and need not be present concurrently. SLICC: Systemic Lupus International Collaborating Clinics, SLE: systemic lupus erythematosus, ANA: antinuclear antibody, anti-dsdna: anti-double-stranded DNA, ELISA: enzyme-linked immunosorbent assay. 근부위 (deltoid), 어깨뒤쪽, 목을포함하는부위 ( 숄징후, shawl sign); 목앞쪽과가슴위쪽, 얼굴중앙부위, 눈주위, 이마, 두피등에나타난다 (24). 피부근염에서질병특유증상은 Gottron's papule과 Gottron's sign인데, Gottron's sign은팔꿈치, 무릎, 손가락마디, 대전자 (greater trochanters), medial malleoli 등뼈가나온부위에보이는적자색홍반이며, Gottron's papule은손가락관절배부에발생한인설을동반한적자색구진이다. 피부근염에서질병특유하지는않지만특징적인소견으로는눈주변의연자색홍반 (heliotrope erythema), 조갑주위모세혈관확장증, dystrophic cuticle, 광노출부위의연자색홍반등이있다. 이염증성피부병변은 LE의피부병변과달리가려움증이나화끈거림을나타낸다 (23). 이외에도 poikiloderma atrophicans vasculare ( 다형피부근염, poikilodermatomyositis), 피부석회증 (calcinosis cutis) 도특징적이다. 피부병변은자외선에의해발생혹은악화되는경향이많으며환자의약 50% 에서광과민성을보인다. 기타피부소견여러가지피부증상이동반될수있다. 흑색극세포증 (steroid-induced acanthosis nigricans), 후천성어린선 (acquired ichthyosis), 전신부종 (anasarca), 안면부종, 홍피증 (erythroderma), 모공성과각화증 (follicular hyperkeratosis), 다모증 (hypertrichosis), 편평태선 (lichen planus), linear immunoglobulin A bullous dermatosis, 망상청피반 (livedo reticularis), 연화판 (malakoplakia), malignant atrophic papulosis, 점액증 (mucinosis), mucous membrane lesions, 비중격천공 (nasal septal perforation), 피하지방층염 (panniculitis), 두드러기, 백혈구파괴성혈관염 (leukocytoclastic vasculitis) 등이다 (25). 병리조직학적소견피부근염의초기조직학적소견은거의정상피부와다르지않으나임상적으로연자색홍반으로발전하면 LE와구별이되지않는소견을보인다. 병변의진피-표피경계부에서면역글로불린과보체의침착이면역조직학적으로확인되는경우는 5 86% 의환자에서볼수있으나조직검사부위에따라매우달라질수있다 (24). 근무병성또는저근육병성피부근염 (Amyopathic or hypomyopathic dermatomyositis, ADM, HDM) 현재피부근염의진단기준에는근육염증이반드시포함되어야만한다. 그러나전형적인피부근염환자의 60% 는피부과근육의변화는동시에관찰할수있는반면, 30% 는피부병변이근육의변화보다수주또는수개월앞선다. 즉근육의이상이임상적또는검사실소견에나타나기전 6개월이상전형적인피부증상만을호소하는환자들이있고, 이런환자들은미국의대학병원피부과에서진료하는전체피부근염환자의 10 20% 를차지한다 (26). 이런경우 ADM 또는 HDM 이라고할수있다. 성인피부근염환자의 20 25% 는내부장기암이동반되는데이는나이가많을수록더높아지고발병후 3년후에는감소된다고알려져있는데비해 ADM과 HDM은피부근염보다암발생위험이적다 (odds ratio, 4.61) (27). 또한간질성폐질환도전형적인피부근염환자 10 40% 에서동반되는데비해 ADM과 HDM은 11% 이었다. 치료피부근염은가려움증이나따가운증상이심하므로이에대한국소치료제, 스테로이드연고등으로치료해야한다.

7 류마티스질환의피부소견 215 피부증상은자외선에의해악화되므로자외선을차단하는것이매우중요하다. 전형적인피부근염에서는전신적인스테로이드제투여가 1차치료이다. 질병초기에사용하면예후가좋아질수있다. 장기간스테로이드치료의부작용을감소하기위하여 azathioprine, cyclophosphamide, methotrexate, chlorambucil, cyclosporine, mycophenolate 등을사용한다. 치료에저항하는경우에는고용량의정맥내면역글로불린이사용된다. 그러나면역억제제사용에앞서항히스타민제와항염증치료제인 hydroxychloroquine, dapsone 등을우선사용하는것이좋다 (24,25). 최근에는생물학적제제인 TNFα 억제제치료가효과를보였다는보고가있고 (28), 다른생물학적제제인 rituximab의효과에대한보고도있다 (29). 경피증 (Scleroderma) 피부의경화증 (sclerosis of the skin) 은전신경화증 (systemic sclerosis) 의피부증상일뿐만아니라 LE나피부근염등에서도나타날수있다. 하지만경피증 (scleroderma) 은피부에국소적혹은광범위하게경화증이나타나는것이유일하거나두드러지는경우에국한하여일컫는다 (30). 경피증은진피에교원질의침착으로인하여피부가두꺼워지며하부조직에부착되어움직이지않는단단하고표면이매끄러운상아색의반혹은반점이국한된부위혹은전신적으로발생하여만성적인경과를취하는결합조직병이다. 경피증을국한피부경화증과전신경화증으로분류하면 Table 3과같다 (25). 이중국한피부경화증 (localized scleroderma) 은국소피부경화증 (morphea) 라고하며가락피부경화증 (sclerodactyly), 레이노현상, 조갑주위의혈관확장이없는것으로전신경화증과구별된다 (31). 그러나피 Table 3. Classification of cutaneous sclerosis (scleroderma) (25) 1. Systemic sclerosis (SSc) SSc with diffuse cutaneous scleroderma (syn. Systemic scleroderma, proximal scleroderma) SSc with limited cutaneous scleroderma (syn. CREST syndrome [calcinosis, Raynaud s phenomenon, esophageal dysmotility, sclerodactly, telangiectasia]; acrosclerosis) 2. Localized cutaneous sclerosis (syn. Localized scleroderma, circumscribed scleroderma) Morphea (localized and generalized forms) Plaque, subcutaneous/profunda, guttate, keloidal, superficial, generalized Linear scleroderma Craniofacial En coup de sabre Facial hemiatrophy (syn. Parry Romberg syndrome) Extremities 부, 피하조직, 뼈, 드물게중추신경계에도섬유화가일어나며, morphea 환자들도전신증상, 즉, 피로, 권태감, 관절통, 근육통은물론자가항체양성을보일수있어감별이어렵다. 여기에서는 morphea에대해서주로기술하고자한다. 임상증상 Morphea는여성에서약간더많이발생하나성인과어린이의유병율은비슷하다. 모든인종에서발생하지만백인에서더많이발생하는것으로알려져있다. 임상형태에따라구분할수있는데국한성 (circumscribed, plaque), 전신성 (generalized), 선상 (linear), 수포성 (bullous), 심부 (deep) 경피증등으로나눌수있다 (30). 처음에홍반또는적자색반으로시작하여중심부가백색혹은황색을띠며탄력성이소실되고단단하게되는데경계부는자색의띠를보인다. 병변이진행하면딱딱해지며두꺼워진판의형태를띄고, 그표면의색깔은과색소또는저색소변화를보인다 (32). 이중 circumscribed morphea가가장흔하며주로몸통에몇개의굳은판으로나타나서치료를하지않아도 3 5년후에서서히부드러워진다 (31). 전신성 morphea는 3 cm 이상의딱딱한판이 4개이상있거나얼굴과손을제외한신체의 2군데이상의부위를침범할때를일컫는다. 전체 morphea 중드문형태이며자가항체양성또는전신증상소견을많이동반한다 (33). 소아에서는선상경피증이가장흔한형태로밑에있는조직의섬유화와위축이동반된다 (33). 팔, 다리에선상으로발생하여관절을건너가게되면움직이는데불편함을주게된다. 또이마와두피에칼자국모양으로 (En coup de sabre) 나타나거나 Parry-Romberg syndrome로알려진진행성편측얼굴위축의형태로나타날수도있다. 그러나 morphea 환자는전신경화증을시사하는손가락피부경화증 (sclerodactyly) 을보이지않는다 (34). 조직학적소견 Morphea와전신경화증은조직학적소견이동일하다. 초기에는망상진피 (reticular dermis) 혈관주변에림프구침윤을보이며후기에는염증세포침윤은사라지고콜라겐섬유의비후, 땀샘과혈관의소실등이관찰된다 (31). 치료 Morphea의치료는표준화된치료법이없다 (35). 무작위대조시험의결과에서는협대역 (narrowband) 자외선 B와저용량자외선 A1 광선치료와국소 tacrolimus 연고가활발히진행되는 plaque morphea에효과적임이확인되었다. 심한 morphea 의경우에는 methotrexate, 전신스테로이드, 자외선 A1 광선치료의복합요법이가장신뢰성있는치료로권고되었다 (36). 최근 morphea 치료에대한 systematic re-

8 216 이은소 view에서협대역 (narrowband) 자외선 B 광선치료는진행되거나광범위한표재성진피병변에, 자외선 A-1 광선치료는조금더깊은진피병변에추천되었다. Methotrexate, 전신스테로이드의전신투여는심한병변, 빨리진행되는병변, 기능에이상을초래하는병변등에사용하여야하며, calcipotriene 이나 tacrolimus 국소치료제는제한적으로표재성인염증병변에사용할수있다. 이외 calcipotriol, D-penicillamine, interferon gamma, antimalarials 투여는효과가없는것으로확인되었다 (35). 염증성병변이치료효과가가장좋으며, 질병활성도, 심한정도, 진행상황, 병변의깊이등을고려해서치료를결정해야한다. References 1. Obermoser G. Lupus erythematosus and the skin: a journey at times perplexing, usually complex, often challenging, and evermore exhilarating. Lupus 2010;19: Gilliam JN, Sontheimer RD. Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol 1981;4: Sontheimer RD. The lexicon of cutaneous lupus erythematosus--a review and personal perspective on the nomenclature and classification of the cutaneous manifestations of lupus erythematosus. Lupus 1997;6: Costner MI, Sontheimer RD. Lupus Erythematosus. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Dallas NA, eds. Fitzpatrick's Dermatology in General Medicine. 8th ed. New York, McGraw-Hill, Durosaro O, Davis MD, Reed KB, Rohlinger AL. Incidence of cutaneous lupus erythematosus, : a population-based study. Arch Dermatol 2009;145: Kim YS, Lee CW. Clinical features of the skin lesions of patients with chronic cutaneous lupus erythematosus and examination of the factors that are relevant to its transformation to systemic lupus erythematosus. Korean J Dermatol 2009;47: Kwon TE, Kwon OS, Chung JH, Cho KH, Youn JI. A clinicopathological study of chronic cutaneous lupus erythematosus. Korean J Dermatol 1999;37: Tebbe B. Clinical course and prognosis of cutaneous lupus erythematosus. Clin Dermatol 2004;22: Obermoser G, Sontheimer RD, Zelger B. Overview of common, rare and atypical manifestations of cutaneous lupus erythematosus and histopathological correlates. Lupus 2010;19: Sontheimer RD, Henderson CL, Grau RH. Drug-induced subacute cutaneous lupus erythematosus: a paradigm for bedside-to-bench patient-oriented translational clinical investigation. Arch Dermatol Res 2009;301: Lee CW, Kim JS. Clinical features of subacute cutaneous lupus erythematosus among Koreans. Korean J Dermatol 1997;35: Bae YI, Yun SJ, Lee JB, Kim SJ, Won YH, Lee SC. A clinical and epidemiological study of lupus erythematosus at a tertiary referral dermatology clinic in Korea. Lupus 2009;18: Kuhn A, Sticherling M, Bonsmann G. Clinical manifestations of cutaneous lupus erythematosus. J Dtsch Dermatol Ges 2007;5: Werth VP. Clinical manifestations of cutaneous lupus erythematosus. Autoimmun Rev 2005;4: Zecević RD, Vojvodić D, Ristić B, Pavlović MD, Stefanović D, Karadaglić D. Skin lesions--an indicator of disease activity in systemic lupus erythematosus? Lupus 2001;10: Watanabe T, Tsuchida T. Classification of lupus erythematosus based upon cutaneous manifestations. Dermatological, systemic and laboratory findings in 191 patients. Dermatology 1995;190: Albrecht J, Berlin JA, Braverman IM, Callen JP, Connolly MK, Costner MI, et al. Dermatology position paper on the revision of the 1982 ACR criteria for systemic lupus erythematosus. Lupus 2004;13: 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: Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40: Ahn JK. Clinical manifestations and diagnosis of systemic lupus erythematosus. Korean J Med 2010;78: Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012;64: Clarke JT, Werth VP. Rheumatic manifestations of skin disease. Curr Opin Rheumatol 2010;22: Sontheimer RD. Dermatomyositis: an overview of recent progress with emphasis on dermatologic aspects. Dermatol Clin 2002;20: Sontheimer RD, Hansen CB, Costner MI. Dermatomyositis. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Dallas NA, eds. Fitzpatrick's dermatology in general medicine. 8th ed. New York, McGraw-Hill, Sontheimer RD. Skin manifestations of systemic autoimmune connective tissue disease: diagnostics and therapeutics. Best Pract Res Clin Rheumatol 2004;18: Klein RQ, Teal V, Taylor L, Troxel AB, Werth VP. Number, characteristics, and classification of patients with dermatomyositis seen by dermatology and rheumatology departments at a large tertiary medical center. J Am Acad Dermatol 2007;57: Bendewald MJ, Wetter DA, Li X, Davis MD. Incidence of dermatomyositis and clinically amyopathic dermatomyositis: a population-based study in Olmsted County, Minnesota. Arch Dermatol 2010;146: Keystone EC. The utility of tumour necrosis factor blockade in orphan diseases. Ann Rheum Dis 2004;63 Suppl 2:ii79-ii Rios Fernández R, Callejas Rubio JL, Sánchez Cano D,

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