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1 원 저 원발성다한증환자에서피부수분함유량, 경표피수분손실량수치및족부백선과의관계 = Abstract = 중앙대학교의과대학피부과학교실, P&K 피부임상연구센타 1 손인평 석장미 1 박귀영 이갑석 김범준 서성준 김명남 홍창권 Skin Hydration, Transepidermal Water Loss and Relation with Tinea Pedis in Patients with Primary Hyperhidrosis In Pyeong Son, Jang Mi Suk 1, Kui Young Park, Kapsok Li, Beom Joon Kim, Seong Jun Seo, Myeung Nam Kim and Chang Kwun Hong Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea, P&K Skin Research Center, Seoul, Korea 1 Background: Primary hyperhidrosis (PHH) is the disease of production of excessive sweat mainly localized in palm, sole, and craniofacial area. The characteristics of the lesional skin and the relationship with fungal infection in patients with PHH are still not known in Korean literature. Objective: The aim of the present study was to compare the skin hydration and transepidermal water loss (TEWL) in patients with PHH with those in control group and to determine the relation of PPH to tinea pedis. Methods: A prospective case-control study of patients with PHH was conducted. We have measured the skin hydration and TEWL on the skin of palm, sole and forehead in patients with PPH and those in control group. A total of 67 patients with PHH and 50 volunteers of control group were examined for the presence of tinea pedis. Information on the treatment history of tinea pedis were provided by means of reviewing the medical records. Results: Of 67 patients with PHH included, mean age was 28.1 years. Distributional patterns of PHH were palmoplantar (50.7%), isolated palmar (19.4%), isolated plantar (7.5%), and craniofacial (22.4%). Age at onset for palmoplantar HH (12.9±7.5 years) was significantly younger than that of craniofacial HH (26.8±10.5 years) (p < 0.05). Compared with the skin of those in control group, the values of the skin hydration and TEWL were significantly higher in the skin of patients with PHH. The risk of tinea pedis were increased in patients with primary palmoplantar hyperhidrosis compared with controls (Odds ratio: 2.44). Conclusion: Skin physiological parameters of patients with PHH and normal subjects were evaluated by non-invasive skin bioengineering methods which show quantitative modifications in physiological conditions. On the basis of current data, we can expect great advances in the curative value for treatment in patients with PHH. [Korean J Med Mycol 2011; 16(4): ] Key Words: Primary hyperhidrosis, Skin hydration, Transepidermal water loss, Tinea pedis 접수일 : 2011 년 6 월 13 일, 수정일 : 2011 년 6 월 21 일, 최종승인일 : 2011 년 6 월 21 일 별책요청저자 : 김범준, 서울시동작구흑석동 224-1, 중앙대학교병원피부과전화 : (02) , Fax: (02) , beomjoon@unitel.co.kr

2 서 론 객관화하였다. 또한손발바닥다한증환자에서족부백선의빈도를알아보고자하였다. 다한증은체온조절을목적으로땀샘에서분비되고모공을통하여배출되는생리적인현상보다과도한땀의분비가일어나는것을말한다 1. 발병부위에따라국소혹은전신다한증으로구분하며, 원인에따라원발성과속발성으로분류할수있다. 원발성다한증은주로국소적이고대칭적으로손바닥, 발바닥, 겨드랑이, 안면부에많이나타나며, 원인은아직정확하게알려지지않았지만, 콜린성교감신경섬유에의한에크린한선의과도한자극으로인한것으로추정하고있다 2,3. 반면속발성다한증은선천성질환, 내분비질환, 대사성질환, 심혈관계질환, 신경계질환, 약물남용, 척수손상, 당뇨등과같은기저질환으로인하여생길수있으며, 이러한선행질환이해결되면치료되는것으로알려져있다 4,5. 대부분의국소다한증은정서나온도에의한혈관확장자극 (vasodilatory stimuli) 에서비롯되며이와같은비정상적인발한은이차적으로피부감염이나액취증을유발하는데, 피부감염중특히진균감염의빈도가가장높다 6. 이러한이유로다한증환자는대인관계에서심한스트레스를받을수있으며글쓰기, 컴퓨터자판작업등의일상생활에도많은불편을겪는다. 이는다한증환자의사회생활이나직장생활을어렵게하여삶의질을떨어뜨리고심한경우우울증에까지빠지게한다 7. 족부백선은피부사상균에의한족부감염증으로고온다습한환경및밀폐된신발을착용하는경우, 공동목용탕이나수영장을사용하는경우등에서유병률이증가하는것으로알려져있다 8. 따라서손발바닥다한증환자의경우에도과도한발한에의해습도가높게유지되므로족부백선의발생이증가할것으로생각할수있다. 본연구는원발성다한증환자와정상인의피부수분함유량및경표피수분손실량의비교를통해다한증환자의임상적특징을피부측정치로서 재료및방법 1. 연구대상 2009년 12월에서 2011년 3월까지중앙대학교의료원에서겨드랑이다한증을제외한원발성다한증으로진단받은 20세이상 35세이하환자 67 명 ( 남 35명, 여 32명 ) 을연구대상으로하였으며, 이중손발바닥다한증은 52명, 안면부다한증은 15명이었다 (Table 1). 병력조사와함께일반혈액검사, 간기능검사, 소변검사, 갑상선호르몬검사등을시행하여속발성다한증을배제하였으며, 다한증외의특별한피부과질환및신체질환은없었다. 대조군으로는최근 3개월이내에본원에서시행받은건강검진에서이상소견이없고아토피피부염의병력이없는 20세이상 35세이하의자원자중피부과의사에의하여육안적으로피부질환이없다고판정된 50명 ( 남녀각각 25명 ) 의정상인으로하였다. 2. 연구방법 1) 피부수분함유량 (Skin hydration) 먼저측정부위를씻고건조시킨후공기의이동과직사광선이없는실내온도 20~25, 습도 40~60% 의항온항습조건의밀폐된장소에서 30분의안정을위한다음 Corneometer CM 825 (Courage-Khazaka Electronic GmbH, Köln, Germany) 의탐침을피부표면에가볍게밀착하여측정하였다. 측정부위는손발바닥다한증환자는손바닥과발바닥의정중앙, 안면부다한증환자는이마의정중앙으로하였다. 2) 경표피수분손실량 (Transepidermal water loss; TEWL) 피부수분함유량측정과같은환경조건하에서동일한측정부위를 evaporimeter인 Tewameter TM 210 (Courage-Khazaka electronic GmbH, Köln, Germany) 로측정하였다

3 Table 1. Clinical characteristics of primary hyperhidrosis (N = 67) Age at presentation (N = 67) 28.1±6.9 yr Age at onset, all patterns (N = 67) 16.0±8.9 yr * Age at onset, palmoplantar (N = 52) 12.9±7.5 yr * Age at onset, craniofacial (N = 15) 26.8±10.5 yr * p < 0.05 palmoplantar versus craniofacial Table 2. Distribution of primary hyperhidrosis Site No. (%) Palm and sole 34 (50.7) Palm (isolated) 13 (19.4) Sole (isolated) 5 ( 7.5) Craniofacial 15 (22.4) Total 67 3) 다한증환자에서족부백선의빈도진찰시의족부백선과족부백선의객관적인과거력이있는경우모두를포함하였다. 즉임상적으로족부백선이의심될때 KOH 검사나진균배양검사를통해진균이증명된경우와과거의진료기록에서진균이증명된경우혹은항진균제의사용으로증상이호전되었음을확인할수있는경우로하였다. 4) 통계적분석통계학적분석은 Statistical Package for the Social Sciences (version 12.00; SPSS Inc., Chicago, IL, USA) 프로그램을사용하였다. 환자에대한정보뿐아니라피부수분함유량, 경표피수분손실량등의피부측정치결과를평균 ± 표준편차로나타내었다. 원발성다한증환자와정상인에서의부위별피부측정값과이두군에서의족부백선유병률은 Chi-square test를이용하여분석하였다. 통계결과는 p value가 0.05 미만일때통계학적유의성이있다고판단하였다. 결과 1. 연구대상원발성다한증환자의평균연령은 28.1세였으며, 손발바닥다한증 (12.9±7.5세) 이안면부다한증 (26.8±10.5세) 에비해낮은연령에서증상을보이기시작했다 (Table 1). 대조군인정상인 50명의평균연령은 28.9세였다. 손바닥과발바닥모두에서증상을보인환자가 34명으로가장많았다 (Table 2). Table 3. Corneometer values at involved lesions (A.U. (Arbitray unit)) Corneometer Body site PHH Control * Palm * Sole 2. 기기적측정값 ±21.21 (N = 47) 80.67±15.95 (N = 39) * 55.86±9.57 Forehead (N = 15) PHH: Primary hyperhidrosis * p < 0.05 PHH versus Control 1) 부위별피부수분함유량손바닥에서증상을보이는손발바닥다한증환자의손바닥에서 ±21.21 A.U. (Arbitray unit), 발바닥에서증상을보이는손발바닥다한증환자의발바닥에서 80.67±15.95 A.U., 안면부다한증환자의이마에서 55.86±9.57 A.U. 로측정되었다 (Table 3). 정상인에서는손바닥 62.72±9.41 A.U., 발바닥 45.10±8.67 A.U., 이마 35.25±7.20 A.U. 로나타났다. 2) 부위별경표피수분손실량 62.72± ± ±7.20 손바닥에서증상을보이는손발바닥다한증환자의손바닥에서 65.88±18.25 g/m 2 /h, 발바닥에서증상을보이는손발바닥다한증환자의발바닥에서 48.01±12.54 g/m 2 /h, 안면부다한증환자의이마에서 31.21±10.92 g/m 2 /h로측정되었다 (Table 4). 정상인에서는손바닥에서의측정치가 45.08± g/m 2 /h으로가장높았으며, 다음으로발바

4 Table 4. Transepidermal water loss values at involved lesions (g/m 2 /h) Corneometer Body site PHH Control * Palm * Sole 65.88±18.25 (N = 47) 48.01±12.54 (N = 39) * 31.21±10.92 Forehead (N = 15) PHH: Primary hyperhidrosis * p < 0.05 PHH versus Control 닥 28.95±8.11 g/m 2 /h, 이마는 17.28±7.36 g/m 2 /h로나타났다. 3. 족부백선과의관련성 원발성손발바닥다한증환자 52명중 11명에서진찰시임상적으로족부백선이의심되었으며이중 9명에서 KOH 혹은배양검사에서균의존재를증명할수있었다. 임상적으로의심된 11 명외에 5명에서족부백선의과거력이있음을진료기록을통해확인할수있었다. 일반인중에서는 4명에서임상적으로족부백선이의심되었으며, 4명모두에서균의존재를증명할수있었다. 일반인중추가적으로진료기록으로통해 2명에서족부백선의과거력을알수있었다. 즉, 원발성손발바닥다한증환자의 26.9%, 일반인의 12.0% 를현재혹은과거의족부백선으로진단할수있었으며, 족부백선의상대위험도는 2.24, 교차비는 2.44로나타났다 (Table 5). 고 찰 45.08± ± ±7.36 원발성다한증은기저질환없이정서적자극에의해심해지는과도한발한이나타나는질환으로젊은성인의 2~3% 에서보이며, 주로손바닥이나발바닥에국한되어발생한다 9. 최근다양한피부측정기기의개발과응용으로비침습적인피부평가가가능해졌으며, 지난수십년에걸친 Table 5. Relation between primary palmoplantar hyperhidrosis and tinea pedis Current tinea pedis History of tinea pedis Total PPHH (N = 52) Control (26.9%) 6 (12.0%) PPHH: Primary palmoplantar hyperhidrosis, RR: Relative risk, OR: Odds ratio RR OR 전자공학과의용공학의발달로피부과학에있어많은연구가진행되고있다. 오늘날피부생물공학측정장비 (Skin bioengineering devices) 는피부에직, 간접적으로적용되는약물또는화장품의효과판정에서부터독성학적평가기법에의응용에이르기까지널리이용되고있다. 본연구에서는다한증의임상적특징을객관화하기위해피부를직접측정하여수치로서증상의정도를파악해보고자하였다. Corneometer는전기저항을이용하여탐침이접촉하는곳의정전용량 (capacitance) 을계측하여피부각질층의수분함량을객관적으로측정하는기계로단위는임의단위인 arbitrary unit (AU) 이다 10. 다한증환자에서정상인보다과도한발한을보이는모든부위의수분함유량이월등히높았다. 특히손발바닥다한증환자의손바닥에서그수치가가장높게측정되었다. 따라서다한증환자의치료에서피부수분함유량수치는다한증치료정도의객관적인지표로서이용가능할수있다고판단된다 10. 경표피수분손실량은피부를통한수분의손실을측정하여피부장벽기능을알아보는척도로, 단위시간, 단위면적당피부각질층을통한수분의수동확산량을의미한다 11. 온도와상대습도를극소연산처리 (microcalculating assess) 한후에산출되며, 단위는 g/m 2 /h이다 12. 피부를통하여손실되는수분은단순확산과발한을통한수분손실로나누어지는데, 일반적으로경표피수분손

5 실은피부를통한수분손실의총량을의미하므로땀샘의활성이없을때만각질층의피부장벽기능을반영한다고할수있다 13. 즉, 발한은경표피수분손실의측정을통한피부장벽기능을평가하는데방해요인이될수있다. 질환의특성상발한이측정값에미치는영향을완전히배재할수없지만, 이번연구에서는발한을거의유발하지않는환경조건하에서피부상태측정이이루어졌다. 아토피피부염과같은피부장벽기능이떨어지는피부질환에서는경표피수분손실량이증가하기때문에피부수분함유량은감소하는데 14, 다한증에서는측정부위에따른변수가있지만일반적으로땀샘기능의활성화로인해경표피수분손실량이증가하고피부수분함유량또한증가되어있음을알수있다. 경표피수분손실량또한다한증환자에서치료효과를판정하기위한지표로활용되고있다 15. 표재성피부진균증은피부과외래환자의약 10% 를차지하는비교적빈도가높은질환군이며, 그중에서도족부백선은우리나라에서가장많은백선으로전체백선의 33~40% 를차지한다 16. 백선균의생존과성장을위해서는수소이온농도, 습도, 온도등이중요한요인이며, 특히고온다습한환경요인이백선증을악화시키는데이는높은습도가백선균의생존기간을연장시기때문이다 17. 원발성다한증과족부백선의관계에대한문헌고찰을보면, Walling 6 은원발성다한증환자 387명을대상으로한연구에서피부감염의위험은정상인에비해 3.2배높았으며, 이중진균감염의빈도는 5배높았다고보고하였다. 또한 Leibovici 등 18 은 1,148명의어린이를대상으로한연구에서다한증이있는어린이는 9.9% 에서족부백선을보여다한증이없는어린이에비해 2.4배높은유병률을나타낸다고보고하였으며, Boboschko 등 19 은족부백선이없는일반인에비해족부백선환자에서발바닥다한증이 3.5배높다고보고하였다. 이번연구에서는일반인과비교한원발성다한증환자에서족부백선의상대위험도가 2.24, 교차비는 2.44로나타나이전의 연구와유사한결과를얻을수있었다. 본연구의한계로는경표피수분손실량수치는측정부위별로많게는 20% 정도까지남녀차이가존재할수있는데이를고려하지않은점이다 20,21. 또한본연구에서는이전의보고 6,18,19 에비해서진균감염률이상대적으로낮은것으로조사되었는데, 이는균이증명된경우만을족부백선으로진단하고, 족부백선의과거력은환자의진료기록을통해서만얻은결과이기때문이다. 즉, 임상적으로의심되었으나균을증명하지못한경우, 과거의진료기록이미비하거나타병원에서치료를받은경우등은결과에포함되지않았을수있다. 본연구를통해정상인과비교한다한증환자의임상적인특징을수치로서객관화하여추후다한증의치료효과와관련된연구에서기초자료로서유용하게쓰일수있을것이다. 또한다한증환자에서족부백선의유병률이일반인에비해높은것으로나타나습도가진균의증식에중요한요소임을확인할수있었으며, 다한증환자의생활습관과개인위생의개선에참고가될수있겠다. 결론다한증은과도한발한을특징으로하는임상적으로진단하는질환이지만, 질환의경중이나치료효과등을평가하기위한객관적인피부의검사수치등이없는실정이다. 본연구에서는원발성다한증환자 67명을손발바닥다한증과안면부다한증으로나누어항온항습조건의밀폐된장소에서각각손발바닥의정중앙과이마의정중앙에서피부수분함유량은 Corneometer CM 825 (Courage-Khazaka Electronic GmbH, Köln, Germany) 을, 경표피수분손실량은 Tewameter TM 210 (Courage-Khazaka electronic GmbH, Köln, Germany) 를이용하여측정하였다. 그결과손바닥 ±21.21 A.U., 발바닥 80.67±15.95 A.U., 이마 55.86±9.57 A.U. 로측정되었다. 반면정상인에서는손바닥 62.72±9.41 A.U., 발바닥 45.10±

6 A.U., 이마 35.25±7.20 A.U. 로측정되었다. 다음으로부위별 TEWL 값은손바닥 65.88±18.25 g/ m 2 /h, 발바닥 48.01±12.54 g/m 2 /h, 이마 31.21± g/m 2 /h로측정되었다. 정상인에서는손바닥 45.08±10.26 g/m 2 /h, 발바닥 28.95±8.11 g/m 2 /h, 이마 17.28±7.36 g/m 2 /h로나타났다. 또한원발성손발바닥다한증환자의 26.9%, 일반인의 12.0% 에서현재혹은과거의족부백선으로진단할수있어정상인에비해다한증환자에서족부백선의비율이 2.24배더높아다한증환자에서족부백선이더흔히동반됨을알수있었다. REFERENCES 1. Solish N, Benohanian A, Kowalski JW. Prospective open label study of botulinum toxin type A in patients with axillary hyperhidrosis: effects on functional impairment and quality of life. Dermatol Surg 2005; 31: Haider A, Solish N. Focal hyperhidrosis: diagnosis and management. CMAJ 2005;172: Hornberger J, Grimes K, Naumann M, Glaser DA, Lowe NJ, Naver H, et al. Recognition, diagnosis, and treatment of primary focal hyperhidrosis. J Am Acad Dermatol 2004;51: Thomas I, Brown J, Vafaie J, Schwartz RA. Palmoplantar hyperhidrosis: A therapeutic challenge. Am Fam Physician 2004;69: Kim WO, Kil HK, Yoon DM, Cho MJ. Treatment of Compensatory Gustatory Hyperhidrosis with Topical Glycopyrrolate. Yonsei Med J 2003;44: Walling HW. Primary hyperhidrosis increases the risk of cutaneous infection: A case-control study of 387 patients, J Am Acad Dermatol 2009;61: Solish N, Bertucci V, Dansereau A, Hong HC, Lynde C, Lupin M, et al. A comprehensive approach to the recognition, diagnosis, and severity-based treatment of focal hyperhidrosis: Recommendations of the Canadian hyperhidrosis advisory committee. Dermatol Surg 2007;33: Seo KI, Kim JA, Lim JG, Eun HC, Youn JI. Prevalence of tinea pedis in Korean soldiers in a battalion. Korean J Dermatol 2000;38: Solish N, Benohanian A, Kowalski JW. Prospective open-label study of botulinum toxin type A in patients with axillary hyperhidrosis: effects on functional impairment and quality of life. Dermatol Surg 2005; 31: Ahn SW, Kim YJ, Kim BJ, Kim MN, Lee DH, Huh CH. Comparative study of 20% aluminum chloride solution and botulinum toxin A injection in the treatment of patients with primary palmar hyperhidrosis. Korean J Dermatol 2008;46: Pinnagoda J, Tupker RA, Agner T, Serup J. Guidelines for transepidermal water loss (TEWL) measurement. A report from the standardization group of the european society of contact dermatitis. Contact Dermatitis 1990;22: Blichmann CW, Serup J. Assessment of skin moisture. Measurement of electrical conductance, capacitance and transepidermal water loss. Acta Derm Venereol 1988;68: Pinnagoda J, Tupker RA. Measurement of the transepidermal water loss. In: Serup J, Jemec GBE. Hand book of non-invasive methods and the skin. Boca Raton: CRC press, 1995: Hwang SW, Kang JH, Seol JE, Seo JK, Lee D, Sung HS. The correlation between SCORAD index and instrumental assessment in evaluation of atopic dermatitis severity. Korean J Dermatol 2010;48: Hwang KC, Kim IH, The change of the barrier function of axillary skin and the quality of life in the patients of axillary hyperhidrosis after the injection of botulinum toxin A, Korean J Dermatol 2004;42: KDA Textbook Editing Board. Dermatology. 5 th edition. Seoul:Ryo moon Gak 2008: Suh MK, Sung YO, Yoon KS. A study for the survival period of dermatophytes according to various conditions, Korean J Dermatol 1998;36:

7 18. Leibovici V, Evron R, Dunchin M, Strauss-Leviatan N, Westerman M, Ingber A. Population-based epidemiologic study of tinea pedis in Israeli children. Pediatr Infect Dis J 2002;21: Boboschko I, Jockenhöfer S, Sinkgraven R, Rzany B. Hyperhidrosis as risk factor for tinea pedis. Hautarzt 2005;56: Jang HY, Park CW, Lee CH. A study of transepidermal water loss at various anatomical sites of the skin. Korean J Dermatol 1996;34: Koh JS, Chae KS, Kim HO. Skin characteristics of normal Korean subjects according to sex and site using non-invasive bioengineering methods, Korean J Dermatol 1998;36:

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386-390.hwp 386 HANYANG MEDICAL REVIEWS Vol. 29 No. 4, 2009 우리나라 미숙아의 통계와 의료비용 Statistics and Medical Cost of Preterm in Korea 윤혜선 을지대학교 노원을지병원 소아청소년과학교실 Hye Sun Yoon, M.D., Ph.D., Department of Pediatrics, Nowon