Effective Response of Dermatophytoma Caused by Terbinafine-Resistant Trichophyton interdigitale Solely to Topical Efinaconazole
Effective Response of Dermatophytoma Caused by Terbinafine-Resistant Trichophyton interdigitale Solely to Topical Efinaconazole
复制标题
单纯外用艾芬康唑治疗耐特比萘芬指间毛癣菌引起的皮肤癣菌瘤的有效疗效
DOI：
10.1007/s11046-022-00636-7
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发表时间：
2022
期刊：
影响因子：
5.5
通讯作者：
Kano R.
中科院分区：
文献类型：
--
作者：
Noguchi H;Matsumoto T;Kubo M;Kimura U;Hiruma M;Tanaka M;Yaguchi T;Yamada T;Kano R.
一位68岁的男性兽医，没有严重的健康史，也没有潜在的疾病，于2021年4月因左侧大脚趾甲的黄色变色而到我们诊所就诊。2013至2017年间，他的左脚长期患有角化性过度的足癣，间歇性地使用局部托尔奈夫特(SQLE抑制剂)治疗。临床亚型为指甲下远端和外侧甲下真菌病伴纵向白甲，受累百分比为30%(图像J 1.48v；NIH，美国马里兰州贝塞斯达)(图1a)。直接显微镜下可见丰富的菌丝体和较大的分生孢子，显示为皮肤真菌瘤(图1b)。高碘酸-席夫染色显示菌丝和节孢子分隔。阳性染色反映生物膜中有胞外多糖(图1c)。4周后，在25℃的萨布鲁葡萄糖琼脂上分离到指间毛霉菌(图1d)。该分离株的内部转录间隔区1序列(303/303bp)与GenBank(GenBank)上的菌株CBS 428.63NT完全相同，并用IFM 67,632保存。根据临床和实验室标准协会M38-A2方案进行抗真菌药敏试验。最低抑菌浓度(MIC)分别为：两性霉素B 2μg/m L、依非康唑B 0.015μg/m L、福司拉武康唑0.03μg/m L、伊曲康唑0.06μg/m L、卢利康唑B 0.008、特比奈芬0.5μg/m L、伏立康唑0.0 6μg/m L。用聚合酶链式反应扩增Sqle基因，并进行序列测定。Sqle基因内的单核苷酸替换(1189-TTC？TTA)，导致Sqle蛋白中的Phe397Leu替换。口服特比奈芬(125 mg/天)3个月后，仍有29%的受累(图1e)。皮肤镜检查(Handyscope；FotoFinder，Bad Birnbach，德国)显示皮肤赘生物瘤，表现为甲板远端边缘附近一个圆形的黄褐色甲下区域，由两条近端的白色细带连接(图1f)。用10%的依非康唑溶液涂于指甲3个月后，患病率降至20%(图1g)，10个月后完全治愈(图1h)。值得注意的是，该患者仅用局部使用依非康唑成功治疗，没有进行甲板清创。甲亢角化型足癣用1%卢利康唑治疗6个月后痊愈。依非那康唑对我们的分离株表现出极好的体外敏感性。我们的病人在临床和病理上被诊断为皮肤真菌瘤。对于皮肤生发瘤、纵向白甲症或指甲侧沟受累的病例，手术撕脱患甲是有帮助的。在这种情况下，在甲板上局部给药被证明是有效的，而不需要清创，从而支持了经甲给药途径可以成功穿透皮肤真菌瘤生物膜的观点。依非那康唑抑制羊毛甾醇14-O去甲基酶的作用机制不同
A 68-year-old male veterinarian with no serious health history nor underlying conditions presented to our clinic with yellowish discoloration on the left big toenail in April 2021. He had long-standing hyperkeratotic-type tinea pedis on his left foot intermittently treated with topical tolnaftate (SQLE inhibitor) between 2013 and 2017. The clinical subtype was distal and lateral subungual onychomycosis with longitudinal leukoxanthonychia and the percentage involvement was 30%(Image J 1.48 v; NIH, Bethesda, Maryland, USA)(Fig. 1 a). Direct microscopy revealed abundant mycelia and large conidia, indicating a dermatophytoma (Fig. 1 b). Periodic acid-Schiff staining revealed septate hyphae and arthroconidia. Positive staining reflected extracellular polysaccharides in the biofilm (Fig. 1 c). Trichophyton interdigitale was isolated on Sabouraud dextrose agar at 25 C after 4 weeks (Fig. 1 d). The internal transcribed spacer 1 sequences of the isolate were identical (303/303 bp) to those of T. interdigitale strain CBS 428.63NT (GenBank) and deposited with IFM 67,632. Antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute M38-A2 protocol. The minimum inhibitory concentrations (MICs) were as follows: amphotericin B, 2 μg/mL; efinaconazole, B 0.015 μg/mL; fosravuconazole, 0.03 μg/mL; itraconazole, 0.06 μg/mL; luliconazole, B 0.008; terbinafine, 0.5 μg/mL and voriconazole, 0.06 μg/mL. The SQLE gene was amplified by polymerase chain reaction and sequenced. Single nucleotide substitution within the SQLE gene (1189-TTC? TTA), leading to Phe397Leu substitution within the SQLE protein, was detected. After 3 months of oral terbinafine (125 mg/day) 29% involvement remained (Fig. 1 e). Dermoscopy (Handyscope; FotoFinder, Bad Birnbach, Germany) revealed a dermatophytoma presenting as a round yellowishbrown subungual area near the distal edge of the nail plate connected by two proximal whitish thin bands (Fig. 1 f). Application of efinaconazole 10% solution to the nail for 3 months decreased involvement to 20%(Fig. 1 g) and led to a complete cure after 10 months (Fig. 1 h). Notably, this patient was successfully treated solely with topical efinaconazole and without nail plate debridement. The hyperkeratotic-type tinea pedis was cured after 6 months’ treatment with 1% luliconazole. Efinaconazole demonstrated excellent in vitro sensitivity against our isolate. Our patient was clinically and pathologically diagnosed as dermatophytoma. Surgical avulsion of the affected nail is helpful in cases with dematophytoma, longitudinal leukoxanthonychia or the involvement of the lateral nail sulcus. In this case, the topical administration of efinaconazole on the nail plate proved to be effective without debridement, thus supporting the notion that the transungual route of drug delivery can successfully penetrate the biofilm of the dermatophytoma. Efinaconazole inhibits lanosterol 14-o demethylase, showing a different mechanism of