pissn: eissn: Allergy Asthma Respir Dis 1(1):79-83, March ORIGINAL ARTICLE SCORing

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1 pissn: eissn: (1):79-83, March ORIGINAL ARTICLE SCORing atopic dermatitis index 로평가한아토피피부염의중증도와혈액검사와의연관성 박근화, 박종하, 황윤하, 성명순, 김성원 부산성모병원소아청소년과 The correlation between the severity of atopic dermatitis classified by SCORing atopic dermatitis index and the laboratory tests Geun Hwa Park, Jong Ha Park, Yoon Ha Hwang, Myong Sun Sung, Sung Won Kim Department of Pediatrics, Busan St. Mary's Medical Center, Busan, Korea Purpose: SCORing atopic dermatitis (SCORAD) index is the best validated scoring system in atopic dermatitis (AD). But this scoring system has limitation to the interobserver and intraobserver variation. This study was designed to evaluate the correlation between the severity of AD classified by the and the laboratory tests. Methods: We evaluated 67 children admitted in the pediatric allergy and respiratory division of Busan St. Mary s Medical Center from April 1 to 30, was measured by one same physician. The patients were classified into mild to moderate and severe groups by. We identified sex, age and family history of allergic disease. We checked laboratory tests including mycoplasma immunoglobulin (Ig) M, total IgE, eosinophil count, eosinophil cationic protein, specific IgE, total protein, albumin, IgG, IgA, IgM, IgD, and inflammatory index (lactate dehydrogenase, C-reactive protein, erythrocyte sedimentation rate) and skin culture. Results: There were no statistically significant differences between two groups in age, sex, parental allergic history, skin culture, mycoplasma IgM, specific IgE, immunoglobulin, and inflammatory index. The has statistically significant positive correlations with serum total eosinophil count, and total IgE, and negative correlations with total protein, and albumin. Conclusion: Our study suggest that serum total eosinophil count, total IgE, total protein, and albumin can be used to evaluate the severity of AD and make up for the. ( 1(1):79-83, 2013) Keywords: Atopic dermatitis,, Laboratory tests 서론아토피피부염은영유아기와소아기에주로발생하는심한가려움을동반한만성염증성피부질환으로, 전세계적으로 10 20% 의소아에서발생하는소아의가장흔한만성피부질환이다. 1-3) 아토피피부염은천식과비염으로진행하는행진의첫출발이며, 지속적인가려움과반복적인발병으로환자에게육체적, 정신적고통은물론가족모두의삶의질을저하시킨다. 4,5) 아토피피부염의중증도를평가하는것은임상적으로치료전과후의경과를확인하고학문적연구를위해서필요하지만, 6,7) 아토피피부염중증도를평가하 는적절한혈액검사는없다. 8) 현재아토피피부염중증도를평가하기위해가장널리사용되는것은 SCORing atopic dermatitis (SCORAD) index이다. 는 20명이상의피부과의사들로구성된 European Task Force on AD에의해만들어졌으며타당성, 신뢰도, 민감도가여러연구에서다루어졌고확인되었다. 9,10) 하지만, 는검사자에따라평가결과가달라질수있다는문제점이있다. 9,11) 본연구에서는 로평가한아토피피부염의중증도와혈액검사의연관성을확인하고자하였다. Correspondence to: Sung Won Kim Department of Pediatrics, Busan St. Mary's Medical Center, Yongho-ro 232beon-gil, Nam-gu, Busan , Korea Tel: , Fax: , sbdph1@paran.com Received: December 30, 2012 Revised: March 19, 2013 Accepted: March 19, The Korean Academy of Pediatric Allergy and Respiratory Disease The Korean Academy of Asthma, Allergy and Clinical Immunology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (

2 Park GH, et al. The correlation between and the laboratory tests 대상및방법 1. 대상 2011 년 4월 1일부터 30일까지부산성모병원소아청소년과클리닉에서시행하는아토피피부염교육프로그램에참여한 67명의입원환아를대상으로하였으며, 의무기록조사를통해후향적으로연구하였다. 아토피피부염은 1980년 Hanifin과 Raijka가제시한기준에의해진단하였다. 6) 3. 통계분석통계분석은 SPSS ver (SPSS Inc., Chicago, IL, USA) 프로그램을이용하여시행하였다. SCORAD 지수로분류한두군사이의변수에대한차이를알아보기위해독립변수 T 검정 (independent T test), 교차분석을이용하였다. SCORAD 지수와변수사이의상관관계를알아보기위해 Pearson's 상관분석과비모수상관분석을이용하였다. P값이 0.05 미만인경우통계적으로의미가있다고하였다. 2. 방법 1) 문진및이학적검사환아의성별, 나이, 부모의질환 ( 아토피피부염, 비염, 천식, 두드러기, 식품, 접촉성피부염 ) 등에대해조사하였다. 2) 아토피피부염의중증도를분류하는방법으로 SCORAD 지수를이용하였다. SCORAD 지수는피부병변의범위 (A), 병변의심한정도 (B), 주관적증상 (C) 의 3가지항목으로구성된다. 피부병변의범위는 9의법칙 을이용하여염증부분을평가한다. 이때건조한부분은범위에포함하지않으며최대점수는 100점이다, 병변의심한정도는 6개의임상증상 ( 홍반, 부종 / 구진양, 삼출 / 가피, 줄까짐, 태선화 ) 을 0 3점으로평가하고최대점수는 18점이다. 주관적증상은지난 3일동안의가려움증, 수면장애를 0 10 점으로평가하고최대점수는 20점이다. 3항목의점수를 A/5+7B/2+C 수식을사용하여계산하고최대점수는 103점이다. 본연구에서는중증도를 SCORAD 지수가 50 미만인경우경 중등증군으로, 50 이상인경우중증군으로정의하였다. 한명의의사가모든환아에대한 SCO- RAD 지수를측정하였다. 3) 혈액검사일반혈액검사를시행하여혈청총호산구수, 단백, 알부민, C- 반응단백, lactate dehydrogenase (LDH), 적혈구침강속도 (erythrocyte sedimentation rate, ESR), Mycoplasma IgM, 면역글로불린 (immunoglobulin) G, A, M, D를알아보았고, ImmunoCAP system (Phadia AB, Uppsala, Sweden) 을이용하여총 IgE, 항원특이 IgE ( 집먼지진드기 [Dermatophagoides farinae, Dermatophagoides pteronyssinus], 달걀, 우유, 밀, 콩, 땅콩 ), 호산구양이온단백 (eosinophil cationic protein, ECP) 등을확인하였다. 항원특이 IgE 는 0.35 kua/l 이상일경우양성으로정의하였다. 4) 피부세균배양검사입원후치료시작전에환아의병변중삼출성부분을면봉으로닦아내고수송배지에넣어검사실로보내어세균배양을하였다. 1. 문진및이학적검사 결과 4 개월에서 9 세까지의환아총 67 명중남아 38 명 (56.7%), 여아 29 명 (43.3%) 이었고, 경 중등증군 49 명 (73.1%), 중증군 18 명 (26.9%) 이 었다. 평균연령은경 중등증군 ( 남아 27 명, 여아 22 명 ) 은 1.45± 0.24 세, 중증군 ( 남아 11 명, 여아 7 명 ) 2.26±0.65 세이었다. 만 24 개 월미만인환아는경 중등증군 38 명 (77.6%), 중증군 12 명 (66.7%) 이었다. 부모가질환이있는경우는경 중등군 38 명 (77.6%), 중증 군 16 명 (88.9%) 이었다. 부모의질환중아토피피부염, 식품은두군 에서통계학적으로유의한차이가없었으며, 중증군에서비염 17 명 (77.8%), 경 중등증군에서접촉성피부염 16 명 (32.7%) 으로통계 학적으로유의하게높았다 (Table 1). 천식이나두드러기가있었던 부모는없었다. 2. SCORAD 지수 SCORAD 지수와총 IgE, 총호산구수의상관계수는 0.330, 로통계학적으로유의하게양의상관관계가있었다. SCO- RAD 지수와 ECP 의상관계수는 이었다. SCORAD 지수와 혈청단백, 알부민의상관계수는 , 으로통계학적으로 유의하게음의상관관계가있었다 (Fig. 1). Table 1. Comparison of characteristics in study groups Characteristic Mild-moderate Severe P-value Patients 49 (73.1) 18 (26.9) Age (yr) 1.45± ± Male sex 27 (71.1) 11 (28.9) ± ± Parental allergic disease 38 (77.6) 16 (88.9) Atopic dermatitis 18 (36.7) 3 (16.7) Allergic rhinitis 23 (46.9) 14 (77.8) Food allergy 2 (4.0) 0 (0) Allergic contact dermatitis 16 (32.7) 11 (22.4) Values are presented as number (%) or mean± standard deviation. SCORAD, SCORing atopic dermatitis. 80

3 박근화외 와혈액검사와의연관성 Total lge P=0.006, r= ,500 2,000 1,500 1, , ,000 7,000 6,000 5,000 4,000 3,000 2,000 1, A B C Eosinophil count P=0.000, r=0.462 ECP P=0.025, r=0.273 Total protein P=0.000, r= D Albumin P=0.001, r= E Fig. 1. Correlation of SCORing atopic dermatitis (SCORAD) index with total immunoglobulin E (IgE) (A), total eosinophil count (B), eosinophil cationic protein (ECP) (C), total protein (D), albumin (E). 3. 혈액검사두군을비교하였을때총 IgE는경 중등증군 113.5±33.9 IU/ ml, 중증군 400.8±160.2 IU/mL, 총호산구수는경 중등증군 527.6±62.4 /μl, 중증군 1,825.0±499.2/μL, ECP는경 중등증군 27.5±3.9 μg/l, 중증군 59.5±16.3 μg/l이었으며통계학적으로유의하게중증군에서높았다. 항원특이 IgE 양성인경우는통계학적으로유의한차이가없었지만, 달걀항원에대한특이 IgE 양성 ( 0.35 kua/l) 인경우가 18명 (36.7%), 12명 (66.7%) 으로두군에서모두가장높았다. 다른면역글로불린 (IgG, IgA, IgM, IgD) 은두군에서통계학적으로유의한차이가없었다. 혈청단백은 6.34±0.06 g/ dl, 5.98±0.14 g/dl, 알부민은 4.49±0.03 g/dl, 4.26±0.06 g/dl 로통계학적으로유의하게중증군에서낮았다. LDH, CRP, ESR은두군에서통계학적으로유의한차이가없었다. 마이코플라즈마 IgM이양성으로나온경우는 12명 (24.5%), 4명 (22.2%) 으로두군에서통계학적으로유의한차이가없었다 (Table 2). 4. 피부세균배양검사피부세균배양검사결과두군에서 Staphylococcus aureus가 23 명 (46.9%), 12명 (66.7%) 으로모두가장높았다. Staphylococcus epidermidis, Enterobacter cloacae, Sterptococcus species, Enterococcus species 등다른균이배양된경우가 20명 (40.8%), 5명 (27.8%), 균이배양되지않은경우가 6명 (12.2%), 1명 (5.6%) 이었으며통계학적으로유의한차이는없었다 (Table 2). Table 2. Comparison of laboratory tests and skin culture in study groups Variable Mild-moderate (n= 49) Severe (n= 18) P-value Total IgE (IU/mL) 113.5± ± Total eosinophil count (/μl) 527.6± ± ECP (μg/l) 27.5± ± Rate of positive specific IgE House dust mite 7 (14.3) 3 (16.7) Egg 18 (36.7) 12 (66.7) Milk 8 (16.3) 8 (44.4) Wheat 3 (6.1) 3 (16.7) Peanut 9 (18.4) 5 (27.8) Soy 6 (12.2) 5 (27.8) Total protein (g/dl) 6.34± ± Albumin (g/dl) 4.49± ± LDH (U/L) ± ± CRP (mg/dl) 0.92± ± ESR (mm/hr) 4.84± ± Mycoplasma IgM, positive 12 (24.5) 4 (22.2) Skin culture Staphylococcus aureus 23 (46.9) 12 (66.7) Others 20 (40.8) 5 (27.8) No growth 6 (12.2) 1 (5.6) Values are presented as mean± standard deviation or number (%). IgE, immunoglobulin E; ECP, eosinophil cationic protein; LDH, lactate dehydrogenase; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; IgM, immunoglobulin M; Others, Staphylococcus epidermidis, Enterobacter cloacae, Sterptococcus species, Enterococcus species. 81

4 Park GH, et al. The correlation between and the laboratory tests 고찰과거에는아토피피부염의발생빈도가 6세이하어린이의 3% 정도로보고하였으나최근에는전세계적으로어린이의 20% 이상에서발생하는것으로보고하고있다. 12) 우리나라에서도아토피피부염의유병률은증가하고있으며초등학생, 중학생을대상으로조사한결과아토피피부염으로진단받은비율은 1997년 19.7% 에서 2005년 29.2% 로상승하였다고보고하였다. 13) 아토피피부염은다른질환들과마찬가지로완치율이낮고재발률이높아장기간의치료가요구되기때문에환자와부모에게신체적, 정신적, 사회적면등에서삶의질에많은영향을미치고, 아토피피부염의중증도가심할수록삶의질을더욱저하시킨다. 5) 아토피피부염은천식, 알레르기비염이나식품알레르기등다른알레르기질환을동반하는경우가많고, 어린시기에시작된심한아토피피부염일경우동반질환의가능성이더욱높아진다 ) 따라서아토피피부염의빠른진단과중증도평가, 적절한치료는매우중요하다. 아토피피부염은 1980년 Hanifin과 Raijka 6) 가제시한기준에의해증상과징후로진단한다. 혈액검사는아토피피부염을진단하거나아토피피부염의중증도를정확하게평가할수없다. 따라서증상과징후를바탕으로중증도를평가하기위한많은방법들이보고되고있다. 중증도를평가하기위한점수평가법으로, Eczema Area and Severity index, Six Area, Six Sign Atopic Dermatitis index 등이있고, 이중 가가장널리사용되고있다. 9-11) 점수평가법은피부병변의범위와강도를검사자가관찰하고점수를매기는방법이다. 피부병변의범위와강도는경계와정도와명확하지않기때문에검사자에따라평가가달라질수있고, 동일검사자에의한평가일지라도결과가달라질수있다. 하지만혈액검사는중증도를평가하기위한표준방법으로사용되고있지는않지만동일한결과를얻을수있기때문에본연구에서는 에의해평가된아토피피부염의중증도와혈액검사사이의연관성을살펴보고자하였다. 본연구에서는검사자사이의평가차이를줄이기위해동일검사자가모든아토피피부염환아의중증도를분류하였고검사자내의평가차이를줄이기위해단기간동안연구를시행하였다. 총 IgE 농도는아토피피부염환아에서대부분증가되어있고, 최근예후예측인자의가능성이제시되었으며아토피피부염의진단기준중부소견의하나로사용되고있다. 6,18) 총 IgE 농도는아토피피부염의중증도가심해질수록증가한다는보고가있지만총 IgE 농도와중증도사이에상관관계가없다는보고도있어논란이있다 ) 총호산구수는대부분의아토피피부염환아에서증가가관찰되고중증도와상관관계가있다는보고가있다. 하지만심한아토피피부염환아에서정상수치를나타내거나다른알레르기질환에의 해증가된수치를나타낼수있어호산구수와중증도의연관성에대해서도논란이있다. 19,20,22,23) ECP는활성화된호산구의과립에서분비되어단백의한종류로호산구매개염증질환에서호산구의활성도를간접적으로측정할수있는생물학적지표로이용되고있다. 24) ECP 농도는아토피피부염환아에서증가되어있고중증도와연관성이있다는보고가있다. 하지만연관성이없다는보고도있어중증도를반영할수있을지는논란의여지가있다. 19,20,22,25) 본연구에서는혈청총 IgE 농도, 총호산구수, ECP 농도가모두중증군에서경 중등증군보다유의하게높은농도를나타내었고총 IgE, 호산구수는아토피피부염중증도가심해질수록유의하게증가되는양의상관관계가있는것으로나타났다. 아토피피부염이심할경우단백섭취부족, 식품알레르기와관련된소화기관으로의단백소실, 피부삼출성병변으로의단백소실등에의해저단백혈증, 저알부민혈증이동반될수있으며, 26) 아토피피부염이심할수록혈청단백과알부민이감소한다는보고가있다. 27) 본연구에서는중증군이경 중등증군보다혈청 p단백과알부민이유의하게낮았으며중증도가심할수록유의하게감소하는음의상관관계를보였다. 이러한결과를통해혈청총 IgE, 총호산구수, 혈청단백, 알부민이아토피피부염의중증도를반영할수있는혈액검사라고생각한다. 아토피피부염은식품항원과관련성이없다는보고가있으나, 중등도이상의아토피피부염이있는환아에서특히영유아의경우약 40% 에서식품알레르기가있다고보고하고있다. 28) 한연구에서아토피피부염환아중 51% 에서식품항원특이 IgE가양성으로나왔고, 우유 (31%), 달걀 (17.7%), 견과류 (17.7%), 밀가루 (12.2%), 땅콩 (8.8%) 의순으로양성률을보였다. 29) 본연구에서는 67명환아중 35명 (50.7%) 이식품항원특이 IgE 양성으로나왔다. 중증군에서는달걀 (66.7%), 우유, 콩과땅콩, 밀가루순으로높은양성률을보였고, 경 중등증군에서는달걀 (36.7%), 땅콩, 우유, 콩, 밀가루순으로높은양성률을보여두군에서달걀이가장높은양성률을보였다. 모든항원에대해중증군에서더높은양성률을보였지만통계학적으로유의한차이는없었다. 아토피피부염에서피부세균감염은아토피피부염을악화시키는중요한인자로작용하며 90% 정도까지세균이배양되는것으로보고하고있다. 30) 이러한세균중포도알균에대한많은연구가이루어졌다. 31,32) 본연구에서도 67명환아중 60명 (89.6%) 에서세균이배양되었으며두군에서모두황색포도알균이가장높은양성률을나타내어이전연구들과비슷한양상을보였지만중증도와유의한관계는없었다. Mycoplasma pneumoniae 감염은천식의증상악화와연관성이있다고알려져있다. 33,34) 아토피피부염과마이코플라즈마감염의연관성에대한보고는없었으나, 본연구에서는마이코플라즈마감 82

5 박근화외 와혈액검사와의연관성 염에대해 IgM 을확인하고아토피피부염과의연관성, 중증도에따 른차이를확인해보고자하였다. 하지만통계학적인의미는없었다. 본연구에서는혈청총 IgE, 총호산구수, 혈청단백및알부민검 사결과를아토피피부염중증도평가를위한지표로활용할수있 을것으로생각된다. 따라서아토피피부염중증도를평가하기위한 지표로혈액검사를활용할수있을것으로생각한다. 하지만본연 구는단일기관에서적은수의환아를대상으로단기간동안시행 된제한점이있기때문에조금더명확한결론을얻기위해서는추 후추가적인연구가필요할것으로보인다. REFERENCES 1. Williams HC. Clinical practice. Atopic dermatitis. N Engl J Med 2005; 352: Leung DY, Bieber T. Atopic dermatitis. Lancet 2003;361: Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest 2004;113: Mozaffari H, Pourpak Z, Pourseyed S, Farhoodi A, Aghamohammadi A, Movahadi M, et al. Quality of life in atopic dermatitis patients. J Microbiol Immunol Infect 2007;40: Beattie PE, Lewis-Jones MS. A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. Br J Dermatol 2006;155: Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 1980;92: Finlay AY. Measurement of disease activity and outcome in atopic dermatitis. Br J Dermatol 1996;135: Chren MM. Giving "scale" new meaning in dermatology: measurement matters. Arch Dermatol 2000;136: Charman C, Chambers C, Williams H. Measuring atopic dermatitis severity in randomized controlled clinical trials: what exactly are we measuring? J Invest Dermatol 2003;120: Severity scoring of atopic dermatitis: the. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology 1993;186: Oranje AP, Stalder JF, Taieb A, Tasset C, de Longueville M. Scoring of atopic dermatitis by SCORAD using a training atlas by investigators from different disciplines. ETAC Study Group. Early Treatment of the Atopic Child. Pediatr Allergy Immunol 1997;8: Wüthrich B, Schmid-Grendelmeier P. The atopic eczema/dermatitis syndrome. Epidemiology, natural course, and immunology of the IgE-associated ("extrinsic") and the nonallergic ("intrinsic") AEDS. 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