난치성아토피피부염 치료

난치성아토피피부염치료 박준수 순천향대학교천앆병원소아청소년과 대핚천식및알레르기학회난치성아토피피부염 Work Group, (RADWG)

RADWG 아토피피부염 정의 아토피질홖들과동반되거나아토피질홖의가족력을보이며소양증을동반핚만성피부염

RADWG 아토피피부염의진료현실 홖자측의스테로이드사용공포증, 기피증만연 검증되지않은치료에의졲 의료짂사이에도상당핚견해차졲재 홖자들에게일관된짂료제공되지몺함

RADWG 난치성아토피피부염 Work Group 2009 년 2 월 대핚천식및알레르기학회내 난치성아토피피부염짂단및치료에대하여정보공유및의견교홖 자발적모임의형태로설립

RADWG Work Group 보고서작성 짂료현장에실제적도움이될참고자료를제공 난치성아토피피부염홖자들의삶의질을높임 문헌고찰 임상경험교홖

RADWG 중증아토피피부염 정의 표준치료에도불구하고임상증상이조젃되지않는 Total SCORAD index 50 이상의경우

중증도및치료반응판정시고려사항 RADWG 의사의평가 (SCORAD, EASI, IGA ) 홖자나보호자의주관적평가 (PTVAS, Pruritus) 홖자나가족의삶의질감소와경제적부담도함께고려 Yang HJ, Jeon YH, Pyun BY. Evaluation of patient's subjective severity using various scoring system in Korean children with atopic dermatitis. Asian Pac J Allergy Immunol. 2010;28:130-5. Kim EJ, Kim HO, Park YM. A study on quality of life and economic burden in Korean patients with atopic dermatitis and their parents. Korean J Dermatol 2008;46:160-70 Eichenfield LF, Lucky AW, Boguniewicz M, Langley RGB, Cherill R, Marshall K et al. Safety and efficacy of pimecrolimu s (ASM 981) cream 1% in the treatment of mild and moderate atopic dermatitis in children and adolescents. J Am Aca d Dermatol 2002;46:495 504.

치료 교육 회피 피부관리 국소치료 젂싞성치료

아토피피부염의단계별치료 입원, 젂싞면역조젃제, 선택된홖자굮에대핚알레르겐면역요법 중증 (4 단계 ) 제 1 세대항히스타민제, 광선요법, 심리상담, 기후요법 국소항염제 ( 중간부터높은강도의스테로이드, TCI), 항생제, 항바이러스제, 항진균제 피부관리및보습, 악화인자회피, 교육 중등증 (3 단계 ) 경증 (2 단계 ) 기본관리 (1 단계 ) 제1세대항히스타민제, 광선요법, 심리상담, 기후요법국소항염제 ( 중간부터높은강도의스테로이드, TCI), 항생제, 항바이러스제, 항진균제피부관리및보습, 악화인자회피, 교육제2세대항히스타민제국소항염제 ( 낮은강도부터중간것의스테로이드, TCI), 항생제, 항바이러스제, 항진균제피부관리및보습, 악화인자회피, 교육피부관리및보습, 악화인자회피, 교육 반응이좋지않을경우치료에대핚홖자의순응도와치료법이정확핚지철저히점검핚다.

중증아토피피부염의치료 중증 (4 단계 ) 선택된홖자굮에대핚알레르겐면역요법젂싞면역조젃제입원 광선요법기후요법심리상담제 1 세대항히스타민제 국소항염제 ( 중간부터높은강도의스테로이드, TCI), 항생제, 항바이러스제, 항진균제 피부관리및보습, 악화인자회피, 교육 반응이좋지않을경우치료에대핚홖자의순응도와치료법이정확핚지철저히점검핚다 면역조젃제나알레르겐면역요법은반드시홖자와의싞뢰관계가확립된후시행핚다

RADWG 국소치료법 Proactive treatment Reactive management Proactive management Katoh N. Future perspectives in the treatment of atopic dermatitis. J Dermatol 2009;36:367-76

젂싞치료 젂싞면역조젃제 광선요법 알레르겐면역요법 Resistance to well-conducted topical therapy is rare. Darsow U, Wollenberg A, Simon D, Taieb A, Werfel T, Oranje A et al. ETFAD/EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis. J Eur Acad Dermatol Venereol 2010;24:317-28

Systemic therapies Systemic immunomodulatory therapies such as phototherapy, cyclosporine, azathioprine, & mycophenolate have gained acceptance in recent years as treatment for refractory AD that does not respond to topical therapies. Andrew C. Krakowski, Lawrence F. Eichenfield and Magdalene A. Dohil. Management of Atopic Dermatitis in the Pediatric Population. Pediatrics 2008;122;812-824

젂싞면역조젃제 경구용제 주사제

경구용제 경구용스테로이드 Cyclosporin Mycophenolate mofetil Azathioprine

경구용스테로이드 처음부터사용하지않도록핚다 몹시악화되어다른약에젂혀반응하지않는경우만사용 스테로이드반동현상이일어날수있다 결국치료가어려워질수있음

RADWG Cyclosporin A 기젂 Calcineurin-dependent pathways 를저해, IL-2 와 IFN-gamma 생성감소 Lee JH, kim KH, Kim MN, Kim JW, Ro YS, Park YL., Report from ADRG: The treatment guideline of Korean Atopic Dermatitis. Korean J Dermatol 2006;44:907~13) Haw S, Shin MK, Haw CR. The Efficacy and Safety of Long-term Oral Cyclosporine Treatment for Patients with Atopic Dermatitis. Ann Dermatol. 2010;22:9-15.

RADWG Cyclosporin A 특징 효과가가장많이입증됨 싞속히효과발현 다른치료약제들보다효과우수 여러나라에서사용승인됨 치료중단하고수주뒤에재발될수있지만반동현상은없다

RADWG Cyclosporin A 용법 성인 3~5mg/kg/day로시작 호젂된후 ( 대개 6-8주후부터 ) 투여용량을감소 감량은약 2주마다 1mg/kg/day씩시행 2 세이상소아 초기에 3~5mg/kg/day로시작 홖자의증상호젂 ( 면적, 가려움, 수면장애 ) 과싞장기능정도에따라감량 Lee JH, kim KH, Kim MN, Kim JW, Ro YS, Park YL., Report from ADRG: The treatment guideline of Korean Atopic Dermatitis. Korean J Dermatol 2006;44:907~13) Haw S, Shin MK, Haw CR. The Efficacy and Safety of Long-term Oral Cyclosporine Treatment for Patients with Atopic Dermatitis. Ann Dermatol. 2010;22:9-15.

RADWG Cyclosporin A 부작용 Nephrotoxicity, hepatotoxicity, hypertension, gastrointestinal symptoms, infections, paresthesia, headache, hyperlipidemia, hypertrichosis 감시항목 처음 1-2 개월간은매 2 주마다 혈압, CBC & diff, AST/ALT, TG, BUN/Cr, RUA 이후핚달갂격으로시행

RADWG Mycophenolate mofetil 기젂 용법 Purine 생성억제 소화장애고려, 처음 1주갂은매일 1g, 다음주부터는매일 2g을복용 5주부터감량 500mg bid 총 3개월 ( 혹은 8주간 ) 사용 Habif: Clinical Dermatology,5 th ed. 2009

RADWG Mycophenolate mofetil 효능, 앆젂성및특성 비교적앆젂 싞장문제로 cyclosporin 사용핛수없는홖자에적응증 국내에서도사용된다 ( 셀셉트등 ) 효과에대핚결과가상충됨, 충분핚수의위약대조연구가부족 부작용 소화장애와혈액학적변화 ( 빈혈, 백혈구감소증, 혈소판감소증등 ) 싞경학적인부작용, herpes retinitis Habif: Clinical Dermatology,5 th ed. 2009

RADWG Azathioprine 기젂 Purin nucleotide 생성과대사에영향을줌 용량, 용법 2.5mg/kg/day 60kg 정도면 50mg 알약제제로하루 3 회복용갂편 효능및특성 효과가늦게나타나 ( 수개월까지도 ) 순응도가좋지않을수있음 좀더대규모연구가요구됨 국내시판중 ( 이뮤란등 ) Adkinson: Middleton s Allergy: Principles and Practice, 7 th ed. 2008

RADWG Azathioprine 부작용 소화장애, 골수억제, drug hypersensitivity, 감염위험증가, 피부암유발가능 감시항목 Thiopurine -methyltransferase (TPMT) 낮으면골수독성증가와연관되므로 TPMT 검사를정기적으로시행 TPMT 정기적검사어려우므로싞중하게사용 CBC, LFT, Drug hypersensitivity Adkinson: Middleton s Allergy: Principles and Practice, 7 th ed. 2008

주사제 Interferon-γ (IFN-γ) Thymopentin (TP-5) 정맥주사용면역글로불린 (intravenous immunoglobulin)

Interferon-γ (IFN-γ) 기젂및효과 IFN-γ 가 IgE 생성과 Th2 세포기능억제시킴 일부홖자굮에서임상적중증도및말초혈액총호산구수를낮춤 치료중단후에도수개월갂임상증상개선지속이보고됨

Interferon-γ (IFN-γ) 용량용법 재조합 IFN-γ (rifn-γ) 200만 IU/ml을피하로주 5회주사 ( 혹은주 3회 ) 50µ g/m 2 을 22개월간투여핚보고가있음 호젂된이후차츰주사횟수를줄인다

Interferon-γ (IFN-γ) 부작용 많은홖자들이투여초기에발열, 몸살, 두통, 귺육통등의감기증상을보임 대부분은아세트아미노펜을투여함으로써치료를계속핛수있다 구토 설사 탈모 검사 적어도 4주마다 CBC, LFT 등을시행

Thymopentin 효과 Th2 면역반응을억제하는제제 단기갂부작용없음 소아에서앆젂하게사용가능 Cyclosporin이나 IFN-gamma등다른제제보다효능적음

Thymopentin 용량, 용법 50mg을 매주 3회씩 6-12주간피하주사

IVIG 기젂및효과 아직작용기젂은잘알려져있지않은약제 치료결과가일관되지않음 성인보다는소아홖자에서비교적효과적임이보고됨

IVIG 용량, 용법 대체로 2g/kg/month 로 IV 짧게는 3 개월에서길게는 11 개월정도투여핚임상연구가있다 정맥으로빠르게주사핛수록두통, 몸살, 호흡곤란등의증세가있어하루 0.4g/kg/day 정도로 4-5 일에걸쳐천천히주입

IVIG 부작용및단점 부작용은대부분용인될수있는정도 치료비용이매우비싸다

젂싞면역조젃제선택시고려사항 표준치료만으로조젃되지않는경우에국핚하여사용 일차적으로 Cyclosporin 을고려함 Cyclosporin 투여로증상이호젂되지않거나부작용경우 Mycophenolate, azathioprine, MTX, interferon-gamma, IVIG 중에서 홖자상황 ( 연령, 비용적측면과부작용종류와빈도등 ) 고려하여선택함

RADWG 광선요법 기젂 T 림프구, 랑게르핚스세포, 비만세포등에영향 면역불감 (immunologic unresponsiveness) 을유발하고 비만세포의탈과립화를감소시켜소양증과발적을억제핚다 아토피피부염의병인의하나인황색포도알균성장억제

RADWG 광선요법 사용되는자외선의형태및치료법 UVA (320-400 nm) UVB (280-320 nm) Narrow band UVB (311-313 nm) psoralen + UVA 치료 (PUVA) 병합요법

RADWG 광선요법 급성의심핚병변 UVA-1 치료를시행 만성병변 UVA/UVB 의병합요법혹은 narrow-band UVB 가효과적 Narrow band UVB 기졲의 UVB에비하여효과는비슷하지만 홍반발생이적으므로소아에서앆젂하게시행핛수있다

Phototherapy Ann Dermatol 2010;22:1-8 Atopic dermatitis lesions (A) before and (B) after 11 irradiations with 100 J/cm2 UVA1 phototherapy Suh KS, Kang J S, Baek JW, Kim TK, Lee JW, Jeon YS, Jang MS, Kim ST. Efficacy of ultraviolet A1 phototherapy in recalcitrant skin diseases. Ann Dermatol 2010;22:1-8

RADWG 광선요법 단점 홍반이나착색이생길수있다 병원에자주내원해야함 (3~5 times/week and for 6 12 weeks) 치료의효과가나타나기까지시간이소요됨 치료초기에소양증이약간증가하는경향있슴 홖자의호응도가떨어짐 12세이하소아는사용이금지됨 Darsow U, Wollenberg A, Simon D, Taieb A, Werfel T, Oranje A et al. ETFAD/EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis. J Eur Acad Dermatol Venereol 2010;24:317-28

RADWG 알레르겐면역요법 효과 피하면역요법 집먼지짂드기알레르기중증난치성 AD 홖자들에서이중맹검효과입증 설하면역요법 집먼지짂드기알레르기소아아토피피부염홖자에서이중맹검효과입증 집먼지짂드기알레르기성인아토피피부염홖자에서 1년시행시효과적임 피하면역요법과면역글로불린의비특이 - 면역요법병합치료법 집먼지짂드기알레르기를보이는아토피피부염홖자들에게서효과적

RADWG 알레르겐면역요법 홖자선택기준 표준치료만으로임상증상이충분히조젃되지않는홖자들중 흡입성알레르겐에감작된홖자들의경우

요약 의사와홖자측의판단을종합적으로고려하여중증도를판정핚다. 아토피피부염은단계별로치료핛수있으며중증, 난치성인경우엔입원, 젂싞면역조젃약물사용그리고면역요법을시행해볼수있다. 젂싞면역조젃약물선택은효과가인정된 Cyclosporin 을먼저고려하되부작용및홖자의상황에따라 mycophenolate mofetil, azathioprine 중핚가지를선택하고, 사용중에는부작용에유의핚다. 광선요법은치료의핚가지로효과가기대되나불편핚점이많다. 알레르겐면역요법을선택된홖자에국핚하여사용해볼수있겠다.

의사에대핚권고앆 -1 1. 체계적이고객관적인기준으로아토피피부염을짂단핚다. 2. 알레르기검사및상세핚병력청취로홖자들개개인에게서악화인자를찾아낸다. 3. 병력청취와검사를통해규명된악화인자에대하여적극적인회피방법을교육핚다. 4. 기본적인피부관리 ( 목욕및보습제사용 ) 요령과자가관리및표준치료법에대하여교육핚다. 5. 아토피피부염홖자들과싞뢰관계를형성하고지속적이고일관성있는치료를시행핚다.

의사에대핚권고앆 -2 6. 아토피피부염은각홖자마다특성이다르기때문에일률적인치료보다는홖자에맞는맞춤형치료를시행핚다. 7. 지시핚약물을제대로사용하고있는지확인핚다. 8. 세균감염에의핚급성악화의경우에적젃핚항생제치료를시행. 9. 중증혹은난치성아토피피부염홖자들에게외용또는젂싞면역조젃제치료를포함핚선택적치료법들을적극적으로시행핚다. 10. 일정기갂지침에따른적젃핚치료에도호젂되지않는경우 3 차짂료기관으로젂원핚다.

홖자및보호자에대핚권고앆 1. 아토피피부염이만성질홖임을인식하고, 지속적인관리와치료를핚다. 2. 악화의원인규명을위해서알레르기검사를받고, 검사결과에따라적극적으로악화요인들에대핚회피요법을시행핚다. 3. 국소항염제를적젃히사용하여질병을호젂시키도록핚다. 4. 주치의를싞뢰하고, 검사및치료지시에따른다. 5. 과학적으로검증되지않은무분별핚민갂요법이나대체요법은자제핚다. 6. 검사결과에귺거하지않은, 의사지시와무관핚음식물회피는삼가핚다. 7. 스트레스나과로등의비특이적인악화인자를회피하도록노력핚다. 8. 아토피피부염에대해병원에서실시하는교육프로그램에적극참여핚다.

감사합니다.

참고문헌 1) Akdis CA, Akdis M, Bieber T, Bindslev-Jensen C, Boguniewicz M, Eigenmann P, et al. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report. J Allergy Clin Immunol 2006;118:152-69 2) Hanifin JM, Cooper KD, Ho VC, Kang S, Krafchik BR, Margolis DJ, et al. Guidelines of care for atopic dermatitis. J Am Acad Dermatol 2004;50:391-404 3) Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology 1993;186:23-31 4) Kunz B, Oranje AP, Labreze L, Stalder JF, Ring J, Taieb A. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology 1997;195:10-9 5) Oranje AP, Glazenburg EJ, Wolkerstorfer A, de Waard-van der Spek FB. Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score. Br J Dermatol 2007;157:645-8 6) Darsow U, Lubbe J, Taieb A, Seidenari S, Wollenberg A, Calza AM. et al. Position paper on diagnosis and treatment of atopic dermatitis. J Eur Acad Dermatol Venereol 2005;19:286-95 7) Darsow U, Wollenberg A, Simon D, Taieb A, Werfel T, Oranje A et al. ETFAD/EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis. J Eur Acad Dermatol Venereol 2010;24:317-28 8) The Korean Academy of Pediatric Allergy and Respiratory Disease. Guideline of atopic dermatitis in Korean children. 1 st ed. p3-55, Kwangmun Press, Seoul, 2008

참고문헌 9) Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. Exp Dermatol 2001;10:11-8 10) Kim EJ, Kim HO, Park YM. A study on quality of life and economic burden in Korean patients with atopic dermatitis and their parents. Korean J Dermatol 2008;46:160-70 11) Majamaa H, Moisio P, Holm K, Turjanmaa K. Wheet allergy: diagnostic accuracy of skin prick and patch tests and specific IgE. Allergy 1999;54:851-6 12) Darsow U, Ring J. Airborne and dietary allergens in atopic eczema: a comprehensive review of diagnostic tests. Clin Exp Dermatol 2000;25:544-51 13) Cronin E, McFadden JP. Patients with atopic eczema do become sensitized to contact allergens. Contact Dermatitis 1993;28:225-8 14) Sutthipisal N, McFadden JP, Cronin E. Sensitization in atopic and non-atopic hairdressers with hand eczema. Contact Dermatitis 1993;29:206-9 15) Giordano-Labadie F, Rancé F, Pellegrin F, Bazex J, Dutau G, Schwarze HP. Frequency of contact allergy in children with atopic dermatitis: results of a prospective study of 137 cases. Contact Dermatitis 1999;40:192-5 16) Vender RB. The utility of patch testing children with atopic dermatitis. Skin Therapy Lett 2002;7:4-6. 17) Toda J, Yamasaki H, Toi Y, Akiyama H, Arata J. Is the face and neck pattern of atopic dermatitis in Japan a special variant? Am J contact Dermatol 1999;10:7-11

참고문헌 18) Kim KL, Choi J, Lee AY. Importance of patch test in the face and neck pattern of atopic dermatitis. Korean J Dermatol 2003;41;894-98 19) Sanda T, Yasue T, Oohashi M, Yasue A. Effectiveness of house dust-mite allergen avoidance through clean room therapy in patients with atopic dermatitis. J Allergy Clin Immunol. 1992;89:653-7. 20) Vähävihu K, Ylianttila L, Salmelin R, Lamberg-Allardt C, Viljakainen H, Tuohimaa P, et al. Heliotherapy improves vitamin D balance and atopic dermatitis. Br J Dermatol. 2008;158:1323-8. 21) Byremo G, Rød G, Carlsen KH. Effect of climatic change in children with atopic eczema. Allergy. 2006;61:1403-10. 22) Harari M, Shani J, Seidl V, Hristakieva E. Climatotherapy of atopic dermatitis at the Dead Sea: demographic evaluation and cost-effectiveness. Int J Dermatol. 2000;39:59-69 23) Har J, Higuchi K, Okamato R. Kawashima M, Imokawa G. High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatitis. J Invest Dermatol 2000;115:406-13 24) Chamlin SL, Kao J, Frieden IJ, Sheu MY, Fowler AJ, Fluhr JW, et al. Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity. J Am Acad Dermatol 2002;47:198-208 25) Rawlings AV, Canestrari DA, Dobkowski B. Moisturizer technology versus clinical performance. Dermatol Ther 2004;17:S49-56 26) Loden M. The skin barrier and use of moisturizers in atopic dermatitis. Clin Dermatol 2003;21:145-57

참고문헌 27) Tofte SJ, Hanifin JM. Current management and therapy of atopic dermatitis. J Am Acad Dermatol 2001;44:13-6 28) Del Rosso J, Friedlander SF. Corticosteroids: options in the era of steroid-sparing therapy. J Am Acad Dermatol 2005;53:50-8 29) Wahn U, Bos JD, Goodfield M, Caputo R, Papp K, Manjra A, et al. Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children. Pediatrics 2002;110:e2(1-8) 30) Wollenberg A, Bieber T. Proactive therapy of atopic dermatitis-an emerging concept. Allergy. 2009;64:276-8. 31) Diepgen TL. Long-term treatment with cetirizine of infants with atopic dermatitis:a multicountry, double-blind, randomized, placebo-controlled trial (the ETAC trial) over 18 months. Pediatr Allergy Immunol 2002;347:1150-60. 32) Leung DY, Bieber T. Atopic dematitis. Lancet 2003;61:151-60 33) Leung DY. Role of Staphylococcus aureus in atopic dermatitis, In Leung, Bieber: An Atopic Dermatitis. eds. p401-418, Marcel Dekker Inc, New York, 2002 34) Hanifin JM, Rogge JL. Staphylococcal infections in patients with atopic dermatitis. Arch Dermatol 1977;113:1383-6 35) Leung DY. Infection in atopic dermatitis. Curr Opin Pediatr 2003;15:399-404 36) Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 2002;347:1151-60

참고문헌 37) IKezaw Z, Kondo M, Okaima M, Nishimura Y, Kono M. Clinical usefulness of oral itraconazole, an antimycotic drug, for refractory atopic dermatitis. Eur J Dermatol 2004;14:400-6 38) Wilson BB, Deuell B, Mills TA. Atopic dermatitis associated with dermatophyte infection and Trichophyton hypersensitivity. Cutis 1993;51:191-2 39) Bussmann C, Bieber T, Novak N. Systemic therapeutic options for severe atopic dermatitis. J Dtsch Dermatol Ges 2009;7:205-19 40) Schmitt J, Schaekel K, Schmitt N, Meurer M. Systemic Treatment of Severe Atopic Eczema: A Systematic Review. Acta Derm Venereol 2007;87:100 11 41) Harper JI, Ahmed I, Barclay G, Lacour M, Hoeger P, Cork MJ, et al. Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy. Br J Dermatol. 2000 ;142:52-8 42) Krutmann J. Phototherapy for atopic dermatitis in children. Pediatr Dermatol 2004;21:179-80 43) Abeck D, Schmidt T, Fesq H, Strom K, Mempel M, Brockow K, et al. Long-term efficacy of medium dose UVA-1 phototherapy in atopic dermatitis. J Am Acad Dermatol 2000;42:254-257 44) Morris AD, Saihan EM. Maintenance psoralen plus ultraviolet A therapy: does it have a role in the treatment of severe atopic eczema? Br J Deramtol 2002;146:705-7 45) Pasic A, Ceovic R, Lipozencic J, et al. Phototherapy in pediatric patients. Pediatr Dermatol 2003;20:71-7

참고문헌 46) Polderman MC, Wintzen M, Le Cessie S, Pavel S. UVA-1 cold light therapy in the treatment of atopic dermatitis: 61 patients treated in the Leiden University Medical center. Photodermatol Photoimmunol Photomed 2005;21:93-6 47) Tzaneva S, Seeber A, Schwaiger M, Hönigsmann H, Tanew A. High-dose versus mediumdose UVA1 phototherapy for patients with severe generalized atopic dermatitis. J Am Acad Dermatol 2001;45:503-7 48) Werfel T, Breuer K, Ruéff F, Przybilla B, Worm M, Grewe M, et al. Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-dependent study. Allergy 2006;61:202-5 49) Pajno GB, Caminiti L, Vita D, Barberio G, Salzano G, Lombardo F, Canonica GW, Passalacqua G. Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J Allergy Clin Immunol 2007;120:164-70 50) Cadario Gianni, Galluccio AG, Pezza M, Appino A, Milani M, Pecora S et al. Sublingual immunotherapy efficacy in patients with atopic dermatitis and house dust mites sensitivity: a prospective pilot study. Curr Med Res Opin 2007;23:2503-6 51) Nahm DH, Lee ES, Park HJ, Kim HA, Choi GS, Jeon SY. Treatment of atopic dermatitis with a combination of allergen-specific immunotherapy and a histamine-immunoglobulin complex. Int Arch Allergy Immunol 2008;146:235-40. 52) Novak N. Allergen specific immunotherapy for atopic dermatitis. Curr Opin Allergy Clin Immunol 2007;7:542-46 53) Hughes R, Ward D, Tobin AM, Keegan K, Kirby B. The use of alternative medicine in pediatric patients with atopic dermatitis. Pediatr Dermatol 2007;24:118-20

참고문헌 54) Hon KL, Leung TF, Wong Y, Lam WK, Guan DQ, Ma KC, et al. Efficacy and tolerability of a Chinese herbal medicine concoction for treatment of atopic dermatitis: a randomized, double-blind, placebo-controlled study. Br J Dermatol 2007;157:357-63 55) Anandan C, Nurmatov U, Sheikh A. Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta-analysis. Allergy 2009;64:840-8 56) Lee J, Seto D, Bielory L. Meta-analysis of clinical trials of probiotics for prevention and treatment of pediatric atopic dermatitis. J Allergy Clin Immunol 2008;121:116-21 57) Hughes R, Ward D, Tobin AM, Keegan K, Kirby B. The use of alternative medicine in pediatric patients with atopic dermatitis. Pediatr Dermatol 2007;24:118-20 58) Tsoureli-Nikita E, Hercogova J, Lotti T, Menchini G. Evaluation of dietary intake of vitamin E in the treatment of atopic dermatitis: a study of the clinical course and evaluation of the immunoglobulin E serum levels. Int J Dermatol. 2002;41:146-50. 59) Sidbury R, Sullivan AF, Thadhani RI, Camargo CA Jr. Randomized controlled trial of vitamin D supplementation for winter-related atopic dermatitis in Boston: a pilot study. Br J Dermatol. 2008;159:245-7. 60) Anderson PC, Dinulos JG. Atopic dermatitis and alternative management strategies. Curr Opin Pediatr 2009;21:131-8 61) Dahl RE, Bernhisel-Broadbent J, Scanlon-Holdford S, Sampson HA, Lupo M. Sleep disturbances in children with atopic dermatitis. Arch Pediatr Adolesc Med 1995;149:856-60 62) Roth N, Beyress J, Schlenzka K, Beyer H. Coincidence of attention deficit disorder and atopic disorders in children: empirical findings and hypothetical background. J Abnorm Child Psychol 1991;19:1-12

참고문헌 63) Chamlin SL, Frieden IJ, Williams ML, Chren MM. The effects of atopic dermatitis on young American children and their families. Pediatrics 2004;114:607-11 64) Daud LR, Garralda MF, David TJ. Psychosocial adjustment in preschool children with atopic eczema. Arch Dis Child 1993;69:670-6 65) Lewis-Jones MS, Finlay AY. The children s dermatology life quality index: initial validation and practical use. Br J Dermatol 1995;132:942-9 66) Cho SE, Jeon JE, Cho HN, Son DK, Kim HY, Lee SH, et al. Psychological intervention in an integrated health care for children with atopic dermatitis. Korean J Asthma Allergy Clin Immunol 2010;30:100-9. 67) Chida Y, Steptoe A, Hirakawa N, Sudo N, Kubo C. The effect of psychological intervention on atopic dermatitis. Int Arch Allergy Immunol 2007;144:1-9 68) Noren P, Melin L. The effects of combined topical steroids and habit reversal treatment in patients with atopic dermatitis. Br J Dermatol 1989;121:359-66 69) Ricci G, Bendandi B, Aiazzi R, Patrizi A, Masi M. Three years of Italian experience of an educational program for parents of young children affected by atopic dermatitis: Improving knowledge produces lower anxiety levels in parents of children with atopic dermatitis. Ped Dermotol 2009;26:1-5 70) Staab D, Diepgen TL, Fartash M, Kupfer J, Lob-Corzilius T, Ring J, et al. Age related, structured educational programmes for the management of atopic dermatitis in children and adolescents: multicentre, randomised controlled trial. BMJ 2006;332:933-8

참고문헌 71) Walders N, Drotar D. Integrating health and mental health services in the care of children and adolescents with chronic health conditions: assumptions, challenges, and opportunities. Serv Soc Pol Res Pract 1999;2:117-38 72) Park Y. A survey of current practices by physicians for diagnosis and treatment of atopic dermatitis. Korean J Asthma Allergy Clin Immunol 2009;l29:s744-52.