长脉冲1064 nm Nd:YAG激光联合特比萘芬治疗Fonsecaea nubica所致着色芽生菌病及其对大鼠模型作用  

Long-pulsed 1064 nm Nd: YAG laser combined with terbinafine against chromoblastomycosis caused by Fonsecaea nubica and the effect of laser therapy in a Wistar rat model

作　　者：罗娟 冯佩英[2] 胡永轩 杨烨玫 周思彤 黄松根 Jadad Abdullah 钟泽敏 郑雨诗 刘康兴 卢艳 胡燕卿 周冼苡 LUO Juan;FENG Peiying;HU Yongxuan;YANG Yemei;ZHOU Sitong;HUANG Songgen;ZHONG Zemin;ZHENG Yushi;LIU Kangxing;LU Yan;HU Yanqing;ZHOU Xianyi(Department of Dermatology and Venerology,Third Affiliated Hospital of Southern Medical University,Guangzhou 510630,China;Department of Dermatology and Venerology,Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]南方医科大学第三附属医院皮肤科,广东广州510630 [2]中山大学附属第三医院皮肤科,广东广州510630

出　　处：《南方医科大学学报》2019年第6期712-717,共6页Journal of Southern Medical University

基　　金：广东省科技计划项目(2013B021800141)

摘　　要：报道长脉冲1064nm Nd:YAG激光联合特比萘芬成功治疗Fonsecaea nubica所致着色芽生菌病1例,并探讨F.nubica的真菌学、体外药敏试验和动物实验特点。患者,男,60岁,右手背约30mm×40mm暗红色斑块10个月,无痒痛。皮损KOH直接镜检、组织病理见特征性的硬壳小体;沙堡培养基26℃培养2周见灰黑色绒毛状菌落,小培养镜下见着色霉属特征性枝孢样产孢结构。对所分离的致病菌株进行ITS序列测序鉴定为F.nubica。采用M38-A2方案对该致病菌进行9种抗真菌药物的体外药敏试验,结果显示特比萘芬MIC值最小(0.125μg/mL)。我们应用该F.nubica菌株成功构建了模拟临床的着色芽生菌病Wistar大鼠模型,并使用长脉冲1064nm Nd:YAG激光(脉宽3.0ms、能量24J/cm^2、光斑直径3mm,频率4Hz,间隔30s,照射共3轮)治疗,2次/周连续8次后停用,结果显示经过8次照射可诱导病变组织局部大量淋巴细胞聚集,促进病变恢复,但不能杀灭真菌。临床上,患者经长脉冲1064nm Nd:YAG激光照射(1次/周,剂量同上)联合口服特比萘芬0.25Bid治疗共8周后皮损明显好转,复查真菌学阴性,随访20月无复发。We report a case of chromoblastomycosis caused by Fonsecaea nubica,which was successfully treated by long-pulsed 1064 nm Nd:YAG laser combined with terbinafine.A 60-year- old man was admitted for the presence of a 30 mm× 40 mm erythematous plaque on the dorsum of his right hand for about 10 months without any subjective symptoms.Both microscopic examination and tissue biopsy of the lesion showed characteristic sclerotic bodies of chromoblastomycosis.Lesion tissue culture on SDA at 26 ℃ for 2 weeks resulted in a black colony,and slide culture identified the isolate as Fonsecaea species.ITS sequence analysis of the isolate showed a 99% homology with F.nubica strain KX078407.The in vitro susceptibility of the isolate to 9 antifungal agents was determined using the microdilution method according to the guidelines of CLSI M38-A2 protocol, and terbinafine showed the lowest MIC (0.125 μg/ml).We subsequently established a Wistar rat model of chromoblastomycosis using the clinical isolate F.nubica and treated the rats with long-pulsed 1064 nm Nd:YAG laser (pulse width of 3.0 ms,fluence of 24 J/cm^2,spot size of 3 mm,frequency of 4 Hz,repeated 3 times at an interval of 30 s) twice a week for a total of 8 sessions.Although the laser treatment alone was not able to eliminate the fungi,histopathological examination showed the aggregation of numerous lymphocytes in the local affected tissue,indicating an immune response that consequently facilitate the regression of the lesion.The patient was successfully treated by long-pulsed 1064 nm Nd:YAG laser once a week combined with terbinafine (0.25 /bid) for 8 weeks,and follow-up for 20 months did not reveal any signs of recurrence.

关 键 词：Fonsecaea nubica 着色芽生菌病 WISTAR大鼠 长脉冲1064nmNd:YAG激光 

分 类 号：R756[医药卫生—皮肤病学与性病学]