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1 대한의진균학회지제 7 권제 4 호 2002 증례보고 경구 Fluconazole 투여로완치된 Sporotrichosis 1 예 =Abstract= 경희대학교의과대학피부과학교실 박현호 이무형 A Case of Sporotrichosis Treated with Oral Fluconazole Hyun Ho Park and Mu Hyoung Lee Department of Dermatology, College of Medicine, Kyung Hee University, Seoul, Korea 59-year-old man visited our clinic due to painful ulcer and crust on the left upper arm 12 months ago. On past history, he had been injured by steel pipe on the left forearm 18 months before. We diagnosed him lymphocutaneous sporotrichosis and treated him with fluconazole 200 mg/day for 11 weeks. He was cured without side effect and had no sign of recurrence during 10 months follow up. We noticed that fluconazole is one of the effective and safe drug in the treatment of sporotrichosis. However, it is necessary to clarify the appropriate dose and duration for treatment of sporotrichosis with fluconazole. [Kor J Med Mycol 2002; 7(4): ] Key Words: Sporotrichosis, Fluconzole 서 론 스포로트리쿰증 (Sporotrichosis) 은주로외상에의한상처를통해 Sporotrix shenckii가침입하여발생하는국내에서가장흔한심재성진균증이다. 주로노출부에피하결절또는궤양성병변이발생하며림프관을통해병변이전파될수있다 1,2. 치료는피부에병변이발생하면경구용포화요오드화칼륨용액 (SSKI) 이주로사용되었고 3,4 전신적인감염을일으킨경우 amphotericin B가주로사용되어왔으나부작용이있어사용에주의를요한다 5. 그외에도 griseofulvin, nystatin, clotrimazole, ketoconazole 6 등으로치료하였으나부작용에비해서효과가적어서 별책요청저자 : 박현호, 서울특별시동대문구회기동 1번지, 경희대학교의과대학피부과학교실전화 : (02) , Fax: (02) pibu@nuri.net * 이논문의요지는 2002년 7월제9차대한의진균학회에서발표하였음. 사용되지않고있다. Terbinafine은일부에서좋은효과가보고되어있으며 7,8 itraconazole이부작용이적고효과가좋은것으로밝혀져스포로트리쿰증의일차치료제로서이용되고있다 9~13. Fluconazole은주로크립토코쿠스감염과칸디다감염의치료에이용되며진균감염의위험도가높은환자에서예방적투여제로이용되고있다 14. 일부저자들은스포로트리쿰증의치료에 fluconazole을이용하였으며 15~19 국내에도 1예가보고되어있다 20. 저자들은 59세남자의좌측상지에발생한피부림프관형스포로트리쿰증에대해 fluconazole을투여하고치료효과를경험하여보고한다. 증례환자 : 이 O O, 59세, 남자초진일 : 2001년 6월 13일주소 : 동통을동반한좌측상완부의피부병변현병력 : 18개월전쇠파이프로좌측전완부에찰

대한의진균학회지제 7 권제 4 호 2002 Fig. 1. A. Whitish scar with peripheral pigmentation on the outer side of left forearm. B.

Fine hyphae with round, large conidia along hyphae on direct smear ( 200). 상을입은후무증상의홍색구진과궤양이발생하였으나 6개월전반흔남기면서사라졌으며그와동시에동측상완부에동통을동반한홍색구진과가피로덮인궤양이발생하였고병변크기가증가하였다 (Fig. 1). 과거력 : 특기사항없음.

Outer side of the left upper arm before treatment (A) was improved 5 weeks later (B) and left scar after 11 weeks (C).

2 대한의진균학회지제 7 권제 4 호 2002 Fig. 1. A. Whitish scar with peripheral pigmentation on the outer side of left forearm. B. Erythematous patches, papules, crusts, and ulcers on the inner side of left upper arm. Fig. 2. A. Dark brown colonies on Saboraud's agar at 21 days after inoculation. B. Fine hyphae with round, large conidia along hyphae on direct smear ( 200). 상을입은후무증상의홍색구진과궤양이발생하였으나 6개월전반흔남기면서사라졌으며그와동시에동측상완부에동통을동반한홍색구진과가피로덮인궤양이발생하였고병변크기가증가하였다 (Fig. 1). 과거력 : 특기사항없음. 직업 : 농부가족력 : 특기사항없음. 피부소견 : 좌측상완부의홍색구진과궤양, 손목의반흔 이학적소견 : 피부병변을제외하고는특기소견없음. 검사실소견 : 일반혈액검사, 간기능검사, 매독 Fig. 3. Clinical course of the skin lesion. Outer side of the left upper arm before treatment (A) was improved 5 weeks later (B) and left scar after 11 weeks (C). Inner side of the upper arm before treatment (D) was improved 5 weeks later (E) and left some crust, scar after 11 weeks (F). 혈청검사, 소변검사, 흉부단순촬영에서는정상소견을보였고, 세균배양검사에서는균이배양되지않았다. 병리조직학적소견 : 상완부의궤양부위에서실시한조직검사에서진피에호중구, 림프구, 조직구등의염증세포침윤이관찰되었다. 중심부에호중구, 중간부에상피양세포와거대세포, 가장외측에림프양세포로구성된 3가지띠 (zone) 가관찰되었다. Periodic acid-schiff (PAS) 염색과 Gomori's methenamin silver (GMS) 염색에서포자를관찰할수있었다. 진균학적소견 : KOH 직접도말검사에서는음성이었으며, 긁어서얻은각질과피부생검을통해얻은조직을 Saboraud's 한천배지배양하여초기에

3 는우유빛에서점차암갈색으로변하면서주름이발생하는 sporotrichosis 의특징적인균집락이관찰되었다 (Fig. 2A). 균집락을채취하여시행한직접도말검사에서격막이있고가지를치는균사와둥근분생자 (conidia) 들이뭉쳐있는것이관찰되었다 (Fig. 2B). 치료및경과 : Fluconazole (Difflucan ) 200 mg/day 로 11주간투여하였으며가피발생후병변은점차호전되었다. 11주간투여후실시한진균학적검사와조직검사에서균은발견되지않았으며 10개월이지난현재까지재발소견은보이지않고있다 (Fig. 3). 고찰스포로트리쿰증은주로상처를통해 Sporothrix schenckii가침입하여일어나는심재성진균증이다. Sporothrix schenckii는 25 에서는균사형, 37 에서는효모형으로존재하는이형성균이며주로피부의상처를통해균이접종되어병변을일으킨다. 자연계에널리분포하는진균으로서토양, 나무, 가시, 동물에서발견될수있으며원예가나농부, 광부에서흔하게발생한다. 전세계적으로분포하고있으나열대와온대지방에서자주보고되며나라마다임상양상의차이가있는것으로알려져있다. 균이피부에침입하면피부와피하에결절성병변이발생하여점차화농이나궤양으로발전하고림프관을통해병변이확산되기도하며뼈, 근육, 중추신경계, 호흡기계, 비뇨기계등전신으로감염을일으킬수도있다. 임상형에따라고정피부형, 피부림프관형, 파종형과피부이외부위에발생하는스포로트리쿰증으로나눌수있다 1. 이러한임상형의차이를보이는것은숙주의면역상태, 균의접종부위나양, 균주의병원성차이와관련된것으로생각하며 21, 피부림프관형에서발견되는균주는 35~37 에서배양되지만고정피부형에서는 35 이하에서만배양되는특성을보여각각의임상형에따라다른아형균주가병변을일으킨다는보고도있다 22. 치료로서 SSKI (saturated solution of potassium iodide) 가고정피부형과피부림프관형의주된치료제로사용되어왔으며값이싸고좋은효과를보인 다. 하지만과민반응을일으킬수있고오심, 구토, 갑상선기능장애, 이하선비대등의부작용이많으며거북한맛을내기때문에환자들이처방에따르지못하는어려움도있다 3,4. Amphotericin B는신독성을일으키는부작용때문에피부형에서는사용되지않으며전신적인감염을일으키는스포로트리쿰증에서이용된다 5. Ketoconazole은 imidazole계의광범위항진균제이지만스포로트리쿰에대한치료효과가적고드물게는간독성이나여성형유방을일으키는부작용을일으킬수있어사용되지않고있다 6. Terbinafine은 125~500 mg/day 을투여하여비교적빠른기간에부작용없이효과를보였다고하였으나보고수가많지않아서연구가더필요하다 7,8. 온열요법은고정피부형에서병변에 42~43 의온도를가해주는방법으로서단독요법으로는사용이힘들지만임산부처럼항진균제의복용이어려울때나보조요법으로서시행할수있다. Itraconazole은 triazole계의약제로서부작용이적고피부형이나관절, 내장, 폐등을침범하는전신형스포로트리쿰증의치료제로서효과가있다. 고정피부형또는피부림프관형스포로트리쿰증에서 100~200 mg/day를 3~6개월간투여하여효과가있었으며 9~12, 파종형의경우고용량인 300~400 mg/day 를 3~6개월간투여하여치료시에효과가나타난증례들이보고되어있다 13. 하지만흡수도가위산도에영향을받을수있어위산도가낮아지는질환이있는환자나위산도에영향을주는약제와의병용에주의를요한다 14. Fluconazole은 itraconazole과같은 triazole계의약물로서 ergosterol의생합성을저해함으로써항진균효과를나타내며칸디다, 크립토코쿠스의치료와면역억제환자에서진균감염에대한예방적투여제로서주로이용되어왔다 14. 스포로트리쿰증에대한치료는 Diaz 등 15 이 19명에서 200~400 mg/day를투여하여 13명이반응하였으며 6개월이하의치료기간에 10명이반응하였고추적관찰중에 1명이재발하였다고하였다. Castro 등 16 은 3명에게 200~ 400 mg/day를 91~174일간투여하여부작용없이치료하였고고정피부형이피부림프관형보다약제에반응이좋으며이것은숙주의세포매개성면역상태와관련이있을것이라고하였다. Yoshida 등

4 대한의진균학회지제 7 권제 4 호 2002 은고정피부형에서 200 mg/week를 4개월간투여하여치료하였으며 7개월까지재발이보이지않았다고하였다. Kauffman 등 18 의보고에서는 14명의환자에게 200~800 mg/day를 8.8개월간투여하여 10명이치료되었으며 1년후까지재발은없었다. Ghodsi 등은 19 고정피부형과림프피부형이동시에발생한환자에서 150 mg/week를투여하여 4개월후고정피부형은치료되었으나 6개월의치료에도림프피부형은호전되지않았으며이것은숙주의면역반응뿐아니라다른균주의온도에대한예민도가치료반응에관여하는것으로생각하였다. 김등 20 은림프피부형에서 200 mg/day로 7주간투여하여비교적빠른반응을보였다고하였다. 스포로트리쿰증에서 fluconazole의사용량은대부분의경우 200~400 mg/ day로효과를보이나 800 mg/day를사용하면더욱빠른효과를보인다고하였다 18. 지금까지의보고에서고정피부형에서는 150 mg/week ~ 200 mg/day 로 3~4개월투여하여반응을보였으며피부림프관형에서는 150 mg/day ~ 800 mg/day 로 2~8개월투여하면치료효과를보이는것으로알려져있다. 현재까지 fluconazole은주로전신진균감염을보이는경우에주로이용되어왔으며약제에대한내성등의문제때문에피부진균등에서의사용에논란의여지가있다. 그러나 150 mg/week 등의적은용량으로도단시간내에치료효과가있다면스포로트리쿰증환자에서이용할수있을것으로생각되며앞으로적절한용량과사용기간에대한연구가필요할것으로생각된다. 참고문헌 1. Davis BA. Sporotrichosis. Dermatol Clin 1996; 14: Belknap BS. Sporotrichosis. Dermatol Clin 1989; 7: Sterling JB, Heymann WR. Potassium iodide in dermatology. J Am Acad Dermatol 2000; 43: Habte-Gabr E, Walsh W. Cutaneous sporotrichosis: the old iodide treatment remains effective. Clin Microbiol Infect 2000; 6: Kauffman CA, Hajjeh R, Chapman SW. Practice guidelines for the management of patients with sporotrichosis. Clin Infect Dis 2000; 30: Dismukes WE, Stamm AM, Graybill JR, et al. Treatment of systemic mycoses with ketoconazole: emphasis on toxicity and clinical response in 52 patients. National Institute of Allergy and Infectious Diseases collaborative antifungal study. Ann Intern Med 1983; 98: Perez A. Terbinafine: broad new spectrum of indications in several subcutaneous and systemic and parasitic diseases. Mycoses 1999; 42: Hay RJ. Therapeutic potential of terbinafine in subcutaneous and systemic mycoses. Br J Dermatol 1999; 1416: 원영호, 전선도, 김성진, 이승철. 피부스포로트리쿰증에서 Itraconazole 경구투여의효과에대한관찰. 대한의진균학회지 1998; 3: Karakayali G, Lenk N, Alli N, Gungor E, Artuz F. Itraconazole therapy in lymphocutaneous sporotrichosis: a case report and review of the literature. Cutis 1998; 61: Conti Diaz IA, Civila E, Gezuele E, et al. Treatment of human cutaneous sporotrichosis with itraconazole. Mycoses 1992; 35: Restrepo A, Robledo J, Gomez I, Tabares AM, Gutierrez R. Itraconazole therapy in lymphangitic and cutaneous sporotrichosis. Arch Dermatol 1986; 122: Stalkup JR, Bell K, Rosen T. Disseminated cutaneous sporotrichosis treated with itraconazole. Cutis 2002; 69: Moossavi M, Bagheri B, Scher RK. Systemic antifungal therapy. Dermatol Clin 2001; 19: Diaz M, Negroni R, Montero-Gei F, et al. A Pan- American 5-year study of fluconazole therapy for deep mycoses in the immunocompetent host. Pan- American Study Group. Clin Infect Dis 1992; 14: S Castro LG, Belda Junior W, Cuce LC, Sampaio SA, Stevens DA. Successful treatment of sporotrichosis with oral fluconazole: a report of three cases. Br J

5 Dermatol 1993; 128: Yoshida M, Hiruma M, Tezuka T. A case of sporotrichosis treated successfully with oral fluconazole 200 mg once weekly. Mycoses 1994; 3728: Kauffman CA, Pappas PG, McKinsey DS, et al. Treatment of lymphocutaneous and visceral sporotrichosis with fluconazole. Clin Infect Dis 1996; 22: Ghodsi SZ, Shams S, Naraghi Z, et al. Case report. An unusual case of cutaneous sporotrichosis and its response to weekly fluconazole. Mycoses 2000; 43: 김문범, 오창근, 장호선, 권경술. 경구용 Fluconazole 투여로치유된스포로트리쿰증 1예. 대한의진균학회지 1999; 4: Dellatorre DL, Lattanand A, Buckley HR, Urbach F. Fixed cutaneous sporotrichosis of the face. Successful treatment of a case review of the literature. J Am Acad Dermatol 1982; 6: Kwon-chung KJ. Comparison of isolated of sporothrix schenckii obtained from fixed cutaneous lesions with isolates from other types of lesions. J Infect Dis 1979; 139:

Microsoft Word - 4-서무규.DOC

Microsoft Word - 4-서무규.DOC 증례보고 고정형스포로트리쿰증 2 예 동국대학교의과대학피부과학교실, 진단검사의학교실 *, 병리학교실 ** 이용환 김수호 서무규 하경임 * 김정란 ** = Abstract = Two Cases of Fixed Cutaneous Sporotrichosis Yong Hwan Lee, Soo Ho Kim, Moo Kyu Suh, Gyoung Yim Ha * and Jung