共聚焦激光扫描显微镜在表皮增生性疾病诊断和评估治疗疗效的应用
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摘要
目的：
1.通过共聚焦激光扫描显微镜采集脂溢性角化病和扁平疣图像,探讨脂溢性角化病和扁平疣的CLSM图像特征。为临床对脂溢性角化病和扁平疣影像学诊断提供可靠依据。
2.利用CLSM评估他扎罗汀凝胶联合NB-UVB治疗斑块型银屑病的治疗效果。
方法：
1.通过对经组织病理学确诊的脂溢性角化病和扁平疣的图像分别进行分析,归纳各自相应的特异性诊断指标,并在盲态下采用回顾性分析方法分别对所有图像进行判读,评价CLSM诊断的特异性和敏感性。同时对脂溢性角化病和扁平疣患者CLSM诊断准确率与病理诊断的准确率相比较。
2.利用CLSM分别检测PIS评分、表皮厚度和迂曲毛细血管治疗前后数量变化,评估联合他扎罗汀凝胶和NB-UVB治疗斑块型银屑病是否优于单一NB-UVB治疗
结果：
1.脂溢性角化病和扁平疣的CLSM图像特征和病理图像具有较高的一致性,经卡方检验证实：CLSM脂溢性角化病特异性指标为“脑回状”结构、棘层肥厚、角囊肿。扁平疣的特征性指标为“花团状”结构和空泡细胞。CLSM诊断脂溢性角化病灵敏度为100%,特异度为87.5%,CLSM对扁平疣的诊断灵敏度为89.7%,特异度为90.9%。
2..联合他扎罗汀NB-UVB和单一NB-UVB治疗斑块型银屑病均有效,前者的PIS评分和表皮厚度减少量均优于后者。
结论：
1.CLSM对脂溢性角化病和扁平疣诊断和鉴别诊断具有较高的灵敏性和特异性。
2.联合他扎罗汀凝胶和NB-UVB治疗斑块型银屑病疗效优于单一NB-UVB治疗。
Objective:
1.The aim of the study was to test the applicability of CLSM to the diagnostic discrimination of Seborrheic keratosis and Plane warts.And their architecture aspects observed by Confocal laser scanning microscopy, and to correlate them with routine histopathology.
2.Evaluate the therapeutic efficacy of narrow-band UVB phototherapy in combination with topical tazarotene.to plaque psoriasis.by confocal laser scanning microscopy.
Method:
1.Images of CLSM were contrasted with the histopathology to induce the criteria. Blinded retrospective analysis of the images from the lesions was carried out by the criteria to determine the specificity and sensitivity for diagnosis.
2.Efficacy was assessed separately by means of a modified psoriasis severity index (PSI).The thickenesses of epidermis and amount of capillary were measured before and after the Phototherapy. Aimed to asess whether the addition of tazarotene to narrow-band UVB phototherapy more effective, faster clearing of psoriasis compared with NB-UVB monotherapy
Results:
1.There was a good correlations between the seborrheic keratosis and Plane warts dermoscopic patterns and findings of confocal images.Byχ2 test, multivariate discriminant analysis and binary logistic regression were performed for the identification of the significant features and for testing newly created diagnostic models. Seborrheic keratosis were mostly characterized by"Gyrus-like"structure、acanthosis、horn cysts.Plane warts were mostly characterized by"Flowers-like" Structure and vesicular cell. the sensitivity and specificity of confocal features for the diagnosis of seborrheic keratosis were 100% and 87.5%.the sensitivity and specificity of confocal features for the diagnosis of plane warts were 89.7% and 90.9%.
2.Both treatment modalities notably reduced the PSI scores and the thickness with values being significantly lower in skin areas.But the addition of tazarotene to narrow-band UVB phototherapy more effective, faster clearing of psoriasis compared with NB-UVB monotherapy.
Conclusion:
1.there are high sensitivity and specificity of confocal features for the diagnosised of seborrheic keratosis and plane warts.
2.The addition of tazarotene to narrow-band UVB phototherapy promotes more effective, faster clearing of psoriasis compared with NB-UVB monotherapy
1.通过共聚焦激光扫描显微镜采集脂溢性角化病和扁平疣图像,探讨脂溢性角化病和扁平疣的CLSM图像特征。为临床对脂溢性角化病和扁平疣影像学诊断提供可靠依据。
2.利用CLSM评估他扎罗汀凝胶联合NB-UVB治疗斑块型银屑病的治疗效果。
方法：
1.通过对经组织病理学确诊的脂溢性角化病和扁平疣的图像分别进行分析,归纳各自相应的特异性诊断指标,并在盲态下采用回顾性分析方法分别对所有图像进行判读,评价CLSM诊断的特异性和敏感性。同时对脂溢性角化病和扁平疣患者CLSM诊断准确率与病理诊断的准确率相比较。
2.利用CLSM分别检测PIS评分、表皮厚度和迂曲毛细血管治疗前后数量变化,评估联合他扎罗汀凝胶和NB-UVB治疗斑块型银屑病是否优于单一NB-UVB治疗
结果：
1.脂溢性角化病和扁平疣的CLSM图像特征和病理图像具有较高的一致性,经卡方检验证实：CLSM脂溢性角化病特异性指标为“脑回状”结构、棘层肥厚、角囊肿。扁平疣的特征性指标为“花团状”结构和空泡细胞。CLSM诊断脂溢性角化病灵敏度为100%,特异度为87.5%,CLSM对扁平疣的诊断灵敏度为89.7%,特异度为90.9%。
2..联合他扎罗汀NB-UVB和单一NB-UVB治疗斑块型银屑病均有效,前者的PIS评分和表皮厚度减少量均优于后者。
结论：
1.CLSM对脂溢性角化病和扁平疣诊断和鉴别诊断具有较高的灵敏性和特异性。
2.联合他扎罗汀凝胶和NB-UVB治疗斑块型银屑病疗效优于单一NB-UVB治疗。
Objective:
1.The aim of the study was to test the applicability of CLSM to the diagnostic discrimination of Seborrheic keratosis and Plane warts.And their architecture aspects observed by Confocal laser scanning microscopy, and to correlate them with routine histopathology.
2.Evaluate the therapeutic efficacy of narrow-band UVB phototherapy in combination with topical tazarotene.to plaque psoriasis.by confocal laser scanning microscopy.
Method:
1.Images of CLSM were contrasted with the histopathology to induce the criteria. Blinded retrospective analysis of the images from the lesions was carried out by the criteria to determine the specificity and sensitivity for diagnosis.
2.Efficacy was assessed separately by means of a modified psoriasis severity index (PSI).The thickenesses of epidermis and amount of capillary were measured before and after the Phototherapy. Aimed to asess whether the addition of tazarotene to narrow-band UVB phototherapy more effective, faster clearing of psoriasis compared with NB-UVB monotherapy
Results:
1.There was a good correlations between the seborrheic keratosis and Plane warts dermoscopic patterns and findings of confocal images.Byχ2 test, multivariate discriminant analysis and binary logistic regression were performed for the identification of the significant features and for testing newly created diagnostic models. Seborrheic keratosis were mostly characterized by"Gyrus-like"structure、acanthosis、horn cysts.Plane warts were mostly characterized by"Flowers-like" Structure and vesicular cell. the sensitivity and specificity of confocal features for the diagnosis of seborrheic keratosis were 100% and 87.5%.the sensitivity and specificity of confocal features for the diagnosis of plane warts were 89.7% and 90.9%.
2.Both treatment modalities notably reduced the PSI scores and the thickness with values being significantly lower in skin areas.But the addition of tazarotene to narrow-band UVB phototherapy more effective, faster clearing of psoriasis compared with NB-UVB monotherapy.
Conclusion:
1.there are high sensitivity and specificity of confocal features for the diagnosised of seborrheic keratosis and plane warts.
2.The addition of tazarotene to narrow-band UVB phototherapy promotes more effective, faster clearing of psoriasis compared with NB-UVB monotherapy
引文
[1].Nakamura, H,Hirota, S,Adachi,S.et al.Clonal nature of seborrheic keratoses demonsteated by using the polymorphism of the human androgen receptor locus as a maker[J].Invest Dermotol,2001,116(4):506-510.
[2].赵辨.临床皮肤病学[M].第3版.南京：江苏科学技术出版社.2001,1111-1112.
[3]袁伟,陈晓红,瓦庆彪,等.电子皮肤镜对脂溢性角化病皮损的观察[J].遵义医学院学报,2004,27(3)：235-236.
[4]Cobb,M.W.Human papilloma virus infection[J].J Am Acad Dermatol,1990,22: 547-566.
[5]Weedon,D,Robertson,I.Regressing plane warts-an ultrastructural study [J]. Australas J Dermatol,1978,19(2):65-68.
[6]Tagami,H, Takigawa, M, Ogino,A.et al.Spotaneous regression of plane warts after inflamation:clinical and histologic studies in 25 cases[J]. Arch Dermatol,1977, 113(9):1209-1213.
[7]郑茂荣.遗传性皮肤疾病[M].北京：科学出版社,1989：226.
[8]Yeatman JM,Kilkenny M,Marks R.The prevalence of seborrheic keratoses in an Australian population:dose exposure to sunlight play a part in their frequency[J].Br Dermato,l 1997; 137(3):411-414.
[9]Zhu WY, Leonardi C, Penney NS.Detection of human papil-lomavirus DNA in seborrheic keratosis by polymerase chain reaction[J].Dermato Sc,i 1992; 4:166-71
[10]赵旭传,陈海蓉.545例老年脂溢性角化病患者血脂、血糖及血压测分析[J].中国麻风皮肤病杂志,2007；23(11)：984-5.
[ll]BlokxWA, de Jong EM, deW ilde PC,et al.P16 and P53 expression in (pre) malignantepidermal tumors of renal transplant recipients and im-munocompent individuals[J].Mod Patho,1 2003; 16(9):869-78.
[12]Green CI,Khavari PA.Targets formolecular therapy ofskin cancer[J].Semin CancerBio,l 2004; 14(1):63-9.
[13]Manaka L,Kadono S,KawashimaM,et al.The mechanism of hyperpigmentation in seborrhoeic keratosis involves the high expression of endothelin-converting enzyme-1 alpha and TNF-alpha, which stimulate secretion of endothelin 1[J].British of dermatology,2001,145(6):895-903.
[14]Bord AS,Seborrhoeic keratosis[M],In Barnhill RL.Textbook of Dermatopathology [A].New York:McGraw-Hill,1998,501-502.
[15]高天文,孙建方,马翠玲,等。现代皮肤组织病理学[M].北京：人民卫生出版社。2001,291-292.
[16]冯德祥.21例扁平疣患者的乙肝三系检测分析.温州医学院学报,1918,23：205.
[17]谭凯心.扁平沈43例静脉血19含量测定及其抗病毒疗效观察.皮肤病与性病,1996,18：1-2.
[18]Thomas BF, Arthuw ZE,Klaus W,Irwin MF,et al.Dermatology in General Medicine,Third Edition.McGraw-Book Co,3rd Edition,1987.2355-2361.
[19]Haftek M, Jablonska S, Orth G. Specific cell2mediated immuneity in patients with epidermodysplasia verruciformis and plane warts [J]. Dermatologica,1985, 170 (5):213-220.
[20]李秉煦,王群姬.扁平疣不同时期病毒核壳蛋白L1抗原表达[J].中华皮肤科杂志,2003,36(10)：593.
[21]Thomas BF, Arthur ZE, Klaus Wolff, et al. Dermatology in General Medicine [M].3rd Edition. McGRAW2BOOK COMPANY,1987.2355.
[22]李秉煦,李剑敏,邵笑红.扁平疣的自愈与人乳头瘤病毒活性的关系[J].中国皮肤性病学杂志,2004,18(10)：587-589.
[23]李秉煦,方溪周,杨毅.扁平疣皮损和疣状表皮结构不良皮损的超微结构对照观察[J].临床皮肤科杂志,2003,32(12)：717.
[24]李秉煦,蔡剑锋,邹炳辉,朱启建.扁平疣临床表现不同皮损的病理观察[J].中华皮肤科杂志,2003,36(4)：201-203.
[25]Iwatsuki K,Tagami H,Takigawa M,et al.Plane warts under spontaneous Immunopathology study on celluar constituents leading to the inflammatory reaction[J].Arch Dermatol,1986,122(6):655-659.
[26]Farber,E.M,Nall,M.L,The nature history of psoriasis in 5600 patients[J]. Dermatologica,1974,148:1-18.
[27]Rook,A.J,Wilkinson,D.S.The prevalence,incidence and ecology of diseases of the skin. In:Rook,A.(ed.)Textbook of dermatology.Oxford:Blackwell Scientific,p 31.
[28].赵辨.临床皮肤病学[M].第3版.南京：江苏科学技术出版社.2001.759-772.
[29]RajadhyakshaM, GrossmanM, EsterowitzD, Webb RH, AndersonRR.In vivo confocal scanning laser microscopy of human skin:melanin provides a good contrast [J]. J Invest Dermatol.1995,104(6):946-952.
[30].RajadhyakshaM, Gonza'lez S, Zavislan J, et al.In vivo confocal scanning laser microscopy of human skin II:advances in instrumentation and comparison to histology[J].InvestDermatol.1999,113(3):293-303.
[31]Gonza'lez S, Tannous Z. Real-time in vivo confocal reflectance microscopy of basal cell carcinoma[J].Am Aead Dermatol.2002,47(6):869-874
[32].LangleyRGB, RajadhyakshaM, Dwyer PJ, et al.confocal scanning laser Microscopy of benign and malignant melanocytic skin lesions in vivo[J]. JAm Aead Dermatol.2001,45(3):365-376.
[33]. Astner S, Gonzalez E, Cheung A.Pilot study on the sensitivity and specificity of in vivo reflectance confocal microscopy in the diagnosis of allergic contact dermatitis[J].Journal of the American acadermy of dermatology,53(6):986-992.
[34]J Tachihara R, Choi C, Langley RG, et al. In vivo confocal imaging of pigm ented eccrine pomma. Dermatology,2002,204(3):185-189.
[35]Gonzalez S, Rajadhyaksha M, Gonzalez-Serva A, White WM, Anderson RR. Confocal reflectance imaging of folliculitis in vivo; correlation with routine histology [J]. Cut Pathol 1999;26(4):201-205.
[36]Propperoval, Langley RG.Reflectance-mode confocal microscopy for the Diagnosis of sebaceous hyperplasia in vivo[J]. Arch Dermatol.2007,143(1):134.
[37]Ramsey Markus, Misbah Huzaira, RoxAnderson, et al. A better potassium hydroxide preparation? In vivo diagnosis of tinea with confocal microscopy [J].Arch Dermatol.2001,137(8):1076-1078.
[38].Gonzalez S, Rajadhyaksha M, Rubinstein G, Anderson RR.Characterization of Psoriasis in vivo by reflectance confocal microscopy.[J].Med.1999,30:337-356.
[39]李欢.共聚焦激光扫描显微镜检测银屑病皮损临床意义研究[D].天津医科大学,2008。
[40]Gonzlez S, Swindells K, Rajadhyaksha M, et al.Changing Paradigmsin dermatology:confocal microscopy in clinical and surgical dermatology[J].Clin Dermatol.2003,21(5):359-69.
[41]Selkin B, Rajadhyaksha M, Gonzalez S, et al..In vivoconfocal microscopy in Dermatology[J].Dermatol Clin.2001,19(2):369-77.
[42]AghassiD, AndersonRR, Gonzdlez S.Time-sequence histologic imaging of Laser-treated cherry angiomas with in vivo confocal microscopy[J].Am Acad Dermatol.2000,43(1):37-41.
[43]M Ardigo, I Malizewsky, ML Dell'Anna, E Berardesca, M Picardo.Preliminary evaluation of vitiligo using in vivo reflectance confocal microscopy[J]. JEADV. 2007,21:1344-1350.
[44]Krutmann J,Morita A.Mechanisms of ultraviolet (UV) B and UVA phototherapy[J].Investig Dermatol SympProc,1999,4(1):7-72.
[45]Tomfohrde,J,Silverman,A,Barnes,R.et al..Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q[J]. Science,1994, 264(5162):1141-1145.
[46]MatthewS,D, Fry,L,Powles,A.et al.Evidence that a locus for familial psoriasis maps to chromosome 4q[J].Nature genetics,1996,14(2):231-233.
[47]Trembath,R.C.,C;ogh,R.L.,Rosbothom,J.L.et al.Identification of a major susceptibility gene locus on chromosome 6p and evidence for further disease loci relealed by a two stage genome wide search in psoriasis[J].Hum Mol Genet, 1997,6(5):813-820.
[48]Weinstein, G.D,McCullough,J,Ross, P.Cell kinetic basis for pathophysiology of psoriasis[J].Invenst Dermatol,1985,85(6):579-583.
[49]Barker,J.N.W.N.Pathogenesis of psoriasis[J].Dermatol,1998,25:778-781.
[50]李燕华,毕志刚,蒋艺.紫外线及其辐射的尿刊酸对朗格汉斯细胞功能影响的研究[J].中华皮肤科杂志,2001,34(1)：47-49.
[51]Ozawa M,Ferenczi K,Kikuchi T,et al.312-nanometer ultraviolet B light (narrow-band UVB) induces apoptosis of T cells within psoriatic lesions[J].J Exp Med,1999,189(4):711-718.
[52]Piskin G,Sylva-Steenland RM,Bos JD,et al.T cells in psoriatic lesional skin that survive conventional therapy with NB-UVB radiation display reduced IFN-gamma expression[J].Arch Dermatol Res,2004,295(12):509-516.
[53]Lehmann B,Knuschke P,Meurer M.Effect of UVB radiation emitted from the narrowband TL-01 lamp(311 nm)on the calcitriol synthesis in organotypic cultures of keratinocytes[J].Exp Dermatol,2005,14(2):153.
[54]Dawe RS,Cameron H,Yule S,et al.UV-B phototherapy clears psoriasis through local effects[J].Arch Dermatol,2002,138(8):1071-1076.
[55]Gollnick H, Finzi A, Marks R, et al. Optimising the use of tazarotene in clinical practice:consensus statement from the European advisory panel for tazarotene (Zorac TM). Dermatology (Basel, Switzerland) [serial online].1999;199(1):40-46.
[56]张江安.他扎罗汀(乙炔维甲酸)的研究进展[J].中国皮肤性病学杂志,2001,15(3)：200-201
[57]Dulvic M, Nagpal S, Asane AT, et al. Molecular mechanisms of tazarotene action in psoriasis. [J]. J Am Acad Dermatol,1997,37(2 Pt 3):S18-24.
[58]Mark R. Pharmacokinetics and safety review of tazarotene [J].Am Aced Dermatol,1998,39(4):134-138.
[59]Luo S, Zheng Y, Peng Z, et al. Effects of narrow-band ultraviolet B and tazarotene therapy on keratinocyte proliferation and TIG3 expression. The Journal Of Dermatology [serial online]. October 2008;35(10):651-657.
[60]Behrens S,Grundmann-Kollmann M,Schiener R,et al.Combination phototherapy of psoriasis with narrow-band UVB irradiation and topical tazarotene gel[J].J Am Acad Dermatol,2000,42(3):493-495.
[61]Koo J,Lowe NJ, Lew-Kaya D,et al.Tazarotene plus UVB phototherapy in the treatment of psoriasis[J].J Am Acad Dermatol,2000,43(11):821-828.
[62]Creamer,D,Allen,M.H,Sousa,A.et al.Localization of endothelial proliferation and microvascular expansion in active plaque psoriasis[J],Br J Dermatol,1997,136,859-865.
[63]Brody,I.Dermal epidemal involvment in the evolution of acute eruptive guttate psoriasis vulgaris[J].1984,82(5):465-470.
[64]潘卫利,吴绍熙。银屑病与微循环[J].国外医学皮肤病学分册,1989,001(01)：6-9.
[1]Rajadhyaksha M, Grossman M, Esterowitz D, et al. In vivo confocal scanning laser microscopy of human skin:melan in provides strong contrast[J].Invest Dermatol,1995,104(6):46-952.
[2]Nieholas AsPres, Ian, Egerton, Adrian C Lim, et al. Imaging the skin.Australasian[J]. Dermatol,2003,44:19-27.
[3].刘华绪,郑志忠,任秋实.基于光学共聚焦原理的皮肤在体三维成像系统及应用.[J]中华皮肤科杂志,2006,39：616-619.
[4]Alvarez-Roman R, NaikA, KaliaYN, et al.Visualization of skin Penetration using Confocal laser scanning microscopy. [J].European Journal of Pharmaceytics And Viopharmaceutics.2004,58(2):301-316.
[5]Girkin J.M, McConnell G.Advances in laser sources for confocal and multiphoton microscopy. [J] Microsc Res Tech,2005,67(1):8-14.
[6]Calzavara-Pinton, P; Longo, C; Venturini, M, et al..Reflectance Confocal Microscopy for In Vivo Skin Imaging. [J] Photochemistry and Photobiology,2008, 84(6):1421-1430.
[7]Langley RG, Rajadhyaksha M, Dwyer PJ, et al. Confocal scanning laser mi croscopy of benign and malignant melanocytic skin lesions in vivo[J]. J Am Acad Dermatol,2001,45(3):365-376.
[8]Giovanni Pellacani, Pascale Guitera, Caterina Longo, et al. The Impact of In Vivo Reflectance Confocal Microscopy for the Diagnostic Accuracy of Melanoma and Equivocal Melanocytic Lesions.[J]Journal of Investigative Dermatology.2007,127: 2759-2765.
[9]Pascale Guiteral, Giovanni Pellacani, Caterina Longo,et al. In Vivo Reflectance Confocal Microscopy Enhances Secondary Evaluation of Melanocytic Lesions.[J] Journal of Investigative Dermatology.2009,129(1):131-138;
[10]LangleyRG, Rajadhyaksha M, Dwyer PJ, Sober AJ, Flotte TJ, Anderson RR.Confocal scanning laser microscopy of benign and malignant melanocytic skin lesions in vivo.[J] J Am Acad Dermatol.2001,45(3):365-376.
[11]V. Ahlgrimm-Siess, C. Massone, S. Koller, R.et al.In vivo confocal scanning laser microscopy of common naevi with globular, homogeneous and reticular pattern in dermoscopy[J]British Journal of Dermatology 2008 158(5):1000-1007.
[12]Fain PR, Babu SR, Bennett DC, Spritz RA. HLA class Ⅱ haplotype DRB1*04-DQB1*0301 contributes to risk of familial generalized vitiligo and early disease onset.[J]Pigment Cell Res.2006;19(1):51-57.
[13]M Ardigo, I Malizewsky, ML Dell'Anna, E Berardesca, M Picardo.Preliminary evaluation of vitiligo using in vivo reflectance confocal microscopy[J]. JEADV. 2007,21:1344-1350.
[14]Gonzalez S, Tannous Z.et al. Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma. [J]J Am Acad Dermatol 2002;47(6):869-74.
[15]Marra, DE; Torres, A; Schanbacher, CF, et al.Detection of Residual Basal Cell Carcinoma by In Vivo Confocal Microscopy.[J]Dermatol Surg 2005;31(5):538-541.
[16]Stockfleth E, Kerl H. Guidline Subcommittee of the European Dermatology Forum. Guidlines for the management of actinic keratoses. Eur J Dermatol 2006; 16:599-606.
[17]Braakhuis BJ, Tabor MP, Kummer JA et al. A genetic explanation of Slaughter's concept of field cancerization:evidence and clinical implications[J]. Cancer Res. 2003,63(8):1727-1730.
[18]Aghassi D, Anderson RR, Gonzalez S.et al. Confocal laser microscopic imaging of actinic keratoses in vivo:a preliminary report[J]. J Am Acad Dermatol 2000, 43(1):42-48。
[19]Martina U, MD, Adrienne M, Francisca R, PHD.et al. Clinical Applicability of in vivo Reflectance Confocal Microscopy for the Diagnosis of Actinic Keratoses [J],Dermatol Surg,2008,34(5):610-619.
[20].赵辨.临床皮肤病学[M].第3版.南京：江苏科学技术出版社.2001.599-601.
[21]Hicks SP, Swindells KJ, Middelkamp-Hup MA, et al. Confocal histopathology of irrirant contact derm atitis in vivo and the impact of skin color (black vs white). [J] Am Acad Dermatol.2003,48(5):727-734.
[22]Maritza A. Middelkamp-Hup, H.-Y. Park,et al.Detection of UV-Induced Pigmentary and Epidermal Changes Over Time Using In Vivo Reflectance Confocal Microscopy[J]. Journal of Investigative Dermatology (2006) 126(2):402-407。
[23]Busam KJ,Hester K,Charles C, et al. Detection of clinically amelanotic malignant melanoma and assessment of its margins by in vivo confocal scanning laser microscopy[J]. Arch Dermatol,2001,137(7):923-929.
[24]Tannous Z,Torres A,Gonzalez S, et al.In vivo real-time confocal reflectance microscopy:a noninvasive guide for Mohs micrographic surgery facilitated by aluminum chloride, an excellent contrast enhancer[J]. Dermatol Surg,2003.29(8): 839-846.
[25].Curiel-Lewandrowski C, Williams CM, Swindells KJ.Use of in vivo confocal microscopy in malignant melanoma:an aid in diagnosis and assessment of surgical and nonsurgical therapeutic approaches [J].Arch Dermatol.2004,140(9):1127-1132.
[26]Gonzalez S, Rajadhyaksha M, Rubinstein G, et al. Characterization of psoriasis in vivo by reflectance confocal microscopy[J]. J Med,1999,30(5-6):337-356.
[27]Callen JP. Cutaneous lupus erythematosus:a personal approach to management[J]. Australas J Dermatol 2006; 47(1):13-27.
[28]. Jaworsky C. Connective tissue diseases. Lupus erythematosus. In:Lever's Histopathology of the Skin (Elder DE, Elenitzas R, Johnson BL,Murphy GF, eds),9th edn. Philadelphia:Lippincott Williams & Wilkins,2005; 293-305
[29]. M. Ardigo', I. Maliszewski, C. Cota, A.et al.Preliminary evaluation of in vivo reflectance confocal microscopy features of discoid lupus erythematosus[J].British Journal of Dermatology 2007,156(6):1196-1203
[30]Bystryn JC, Rudolph J. Pemphigus[J]. Lancet 2005; 366(9479):61-73.
[31]Amagai M, Klaus-Kovtun V, Stanley JR. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion [J].Cell 1991; 67(5):869-877.
[32]I. Angelova-Fischer, T. Pfeuti, D. Zillikensl and C. Rose.In vivo confocal laser scanning microscopy for non-invasive diagnosis of pemphigus foliaceus[J].Skin Research and Technology 2009; 15(1):40-44
[33]Ken-ichiro O'goshi, Christian Suihko,JΦrgen Serup.In vivo imaging of Intradermal tattoos by confocal scanning laser microscopy[J] Skin Research and Technology 2006; 12(2):94-98.
[34]Gonzalez S, Rajadhyaksha M, Gonzalez-Serva A, White WM, Anderson RR. Confocal reflectance imaging of folliculitis in vivo; correlation with routine histology [J]. Cut Pathol 1999;26(4):201-205.
[35]Martin J. Gruber, Alexandra Wackernagel, Erika Richtig, et al.Digital image enhancement for in vivo laser scanning microscopy[J]. Skin Research and Technology 2005; 11(4):248-253.
[2].赵辨.临床皮肤病学[M].第3版.南京：江苏科学技术出版社.2001,1111-1112.
[3]袁伟,陈晓红,瓦庆彪,等.电子皮肤镜对脂溢性角化病皮损的观察[J].遵义医学院学报,2004,27(3)：235-236.
[4]Cobb,M.W.Human papilloma virus infection[J].J Am Acad Dermatol,1990,22: 547-566.
[5]Weedon,D,Robertson,I.Regressing plane warts-an ultrastructural study [J]. Australas J Dermatol,1978,19(2):65-68.
[6]Tagami,H, Takigawa, M, Ogino,A.et al.Spotaneous regression of plane warts after inflamation:clinical and histologic studies in 25 cases[J]. Arch Dermatol,1977, 113(9):1209-1213.
[7]郑茂荣.遗传性皮肤疾病[M].北京：科学出版社,1989：226.
[8]Yeatman JM,Kilkenny M,Marks R.The prevalence of seborrheic keratoses in an Australian population:dose exposure to sunlight play a part in their frequency[J].Br Dermato,l 1997; 137(3):411-414.
[9]Zhu WY, Leonardi C, Penney NS.Detection of human papil-lomavirus DNA in seborrheic keratosis by polymerase chain reaction[J].Dermato Sc,i 1992; 4:166-71
[10]赵旭传,陈海蓉.545例老年脂溢性角化病患者血脂、血糖及血压测分析[J].中国麻风皮肤病杂志,2007；23(11)：984-5.
[ll]BlokxWA, de Jong EM, deW ilde PC,et al.P16 and P53 expression in (pre) malignantepidermal tumors of renal transplant recipients and im-munocompent individuals[J].Mod Patho,1 2003; 16(9):869-78.
[12]Green CI,Khavari PA.Targets formolecular therapy ofskin cancer[J].Semin CancerBio,l 2004; 14(1):63-9.
[13]Manaka L,Kadono S,KawashimaM,et al.The mechanism of hyperpigmentation in seborrhoeic keratosis involves the high expression of endothelin-converting enzyme-1 alpha and TNF-alpha, which stimulate secretion of endothelin 1[J].British of dermatology,2001,145(6):895-903.
[14]Bord AS,Seborrhoeic keratosis[M],In Barnhill RL.Textbook of Dermatopathology [A].New York:McGraw-Hill,1998,501-502.
[15]高天文,孙建方,马翠玲,等。现代皮肤组织病理学[M].北京：人民卫生出版社。2001,291-292.
[16]冯德祥.21例扁平疣患者的乙肝三系检测分析.温州医学院学报,1918,23：205.
[17]谭凯心.扁平沈43例静脉血19含量测定及其抗病毒疗效观察.皮肤病与性病,1996,18：1-2.
[18]Thomas BF, Arthuw ZE,Klaus W,Irwin MF,et al.Dermatology in General Medicine,Third Edition.McGraw-Book Co,3rd Edition,1987.2355-2361.
[19]Haftek M, Jablonska S, Orth G. Specific cell2mediated immuneity in patients with epidermodysplasia verruciformis and plane warts [J]. Dermatologica,1985, 170 (5):213-220.
[20]李秉煦,王群姬.扁平疣不同时期病毒核壳蛋白L1抗原表达[J].中华皮肤科杂志,2003,36(10)：593.
[21]Thomas BF, Arthur ZE, Klaus Wolff, et al. Dermatology in General Medicine [M].3rd Edition. McGRAW2BOOK COMPANY,1987.2355.
[22]李秉煦,李剑敏,邵笑红.扁平疣的自愈与人乳头瘤病毒活性的关系[J].中国皮肤性病学杂志,2004,18(10)：587-589.
[23]李秉煦,方溪周,杨毅.扁平疣皮损和疣状表皮结构不良皮损的超微结构对照观察[J].临床皮肤科杂志,2003,32(12)：717.
[24]李秉煦,蔡剑锋,邹炳辉,朱启建.扁平疣临床表现不同皮损的病理观察[J].中华皮肤科杂志,2003,36(4)：201-203.
[25]Iwatsuki K,Tagami H,Takigawa M,et al.Plane warts under spontaneous Immunopathology study on celluar constituents leading to the inflammatory reaction[J].Arch Dermatol,1986,122(6):655-659.
[26]Farber,E.M,Nall,M.L,The nature history of psoriasis in 5600 patients[J]. Dermatologica,1974,148:1-18.
[27]Rook,A.J,Wilkinson,D.S.The prevalence,incidence and ecology of diseases of the skin. In:Rook,A.(ed.)Textbook of dermatology.Oxford:Blackwell Scientific,p 31.
[28].赵辨.临床皮肤病学[M].第3版.南京：江苏科学技术出版社.2001.759-772.
[29]RajadhyakshaM, GrossmanM, EsterowitzD, Webb RH, AndersonRR.In vivo confocal scanning laser microscopy of human skin:melanin provides a good contrast [J]. J Invest Dermatol.1995,104(6):946-952.
[30].RajadhyakshaM, Gonza'lez S, Zavislan J, et al.In vivo confocal scanning laser microscopy of human skin II:advances in instrumentation and comparison to histology[J].InvestDermatol.1999,113(3):293-303.
[31]Gonza'lez S, Tannous Z. Real-time in vivo confocal reflectance microscopy of basal cell carcinoma[J].Am Aead Dermatol.2002,47(6):869-874
[32].LangleyRGB, RajadhyakshaM, Dwyer PJ, et al.confocal scanning laser Microscopy of benign and malignant melanocytic skin lesions in vivo[J]. JAm Aead Dermatol.2001,45(3):365-376.
[33]. Astner S, Gonzalez E, Cheung A.Pilot study on the sensitivity and specificity of in vivo reflectance confocal microscopy in the diagnosis of allergic contact dermatitis[J].Journal of the American acadermy of dermatology,53(6):986-992.
[34]J Tachihara R, Choi C, Langley RG, et al. In vivo confocal imaging of pigm ented eccrine pomma. Dermatology,2002,204(3):185-189.
[35]Gonzalez S, Rajadhyaksha M, Gonzalez-Serva A, White WM, Anderson RR. Confocal reflectance imaging of folliculitis in vivo; correlation with routine histology [J]. Cut Pathol 1999;26(4):201-205.
[36]Propperoval, Langley RG.Reflectance-mode confocal microscopy for the Diagnosis of sebaceous hyperplasia in vivo[J]. Arch Dermatol.2007,143(1):134.
[37]Ramsey Markus, Misbah Huzaira, RoxAnderson, et al. A better potassium hydroxide preparation? In vivo diagnosis of tinea with confocal microscopy [J].Arch Dermatol.2001,137(8):1076-1078.
[38].Gonzalez S, Rajadhyaksha M, Rubinstein G, Anderson RR.Characterization of Psoriasis in vivo by reflectance confocal microscopy.[J].Med.1999,30:337-356.
[39]李欢.共聚焦激光扫描显微镜检测银屑病皮损临床意义研究[D].天津医科大学,2008。
[40]Gonzlez S, Swindells K, Rajadhyaksha M, et al.Changing Paradigmsin dermatology:confocal microscopy in clinical and surgical dermatology[J].Clin Dermatol.2003,21(5):359-69.
[41]Selkin B, Rajadhyaksha M, Gonzalez S, et al..In vivoconfocal microscopy in Dermatology[J].Dermatol Clin.2001,19(2):369-77.
[42]AghassiD, AndersonRR, Gonzdlez S.Time-sequence histologic imaging of Laser-treated cherry angiomas with in vivo confocal microscopy[J].Am Acad Dermatol.2000,43(1):37-41.
[43]M Ardigo, I Malizewsky, ML Dell'Anna, E Berardesca, M Picardo.Preliminary evaluation of vitiligo using in vivo reflectance confocal microscopy[J]. JEADV. 2007,21:1344-1350.
[44]Krutmann J,Morita A.Mechanisms of ultraviolet (UV) B and UVA phototherapy[J].Investig Dermatol SympProc,1999,4(1):7-72.
[45]Tomfohrde,J,Silverman,A,Barnes,R.et al..Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q[J]. Science,1994, 264(5162):1141-1145.
[46]MatthewS,D, Fry,L,Powles,A.et al.Evidence that a locus for familial psoriasis maps to chromosome 4q[J].Nature genetics,1996,14(2):231-233.
[47]Trembath,R.C.,C;ogh,R.L.,Rosbothom,J.L.et al.Identification of a major susceptibility gene locus on chromosome 6p and evidence for further disease loci relealed by a two stage genome wide search in psoriasis[J].Hum Mol Genet, 1997,6(5):813-820.
[48]Weinstein, G.D,McCullough,J,Ross, P.Cell kinetic basis for pathophysiology of psoriasis[J].Invenst Dermatol,1985,85(6):579-583.
[49]Barker,J.N.W.N.Pathogenesis of psoriasis[J].Dermatol,1998,25:778-781.
[50]李燕华,毕志刚,蒋艺.紫外线及其辐射的尿刊酸对朗格汉斯细胞功能影响的研究[J].中华皮肤科杂志,2001,34(1)：47-49.
[51]Ozawa M,Ferenczi K,Kikuchi T,et al.312-nanometer ultraviolet B light (narrow-band UVB) induces apoptosis of T cells within psoriatic lesions[J].J Exp Med,1999,189(4):711-718.
[52]Piskin G,Sylva-Steenland RM,Bos JD,et al.T cells in psoriatic lesional skin that survive conventional therapy with NB-UVB radiation display reduced IFN-gamma expression[J].Arch Dermatol Res,2004,295(12):509-516.
[53]Lehmann B,Knuschke P,Meurer M.Effect of UVB radiation emitted from the narrowband TL-01 lamp(311 nm)on the calcitriol synthesis in organotypic cultures of keratinocytes[J].Exp Dermatol,2005,14(2):153.
[54]Dawe RS,Cameron H,Yule S,et al.UV-B phototherapy clears psoriasis through local effects[J].Arch Dermatol,2002,138(8):1071-1076.
[55]Gollnick H, Finzi A, Marks R, et al. Optimising the use of tazarotene in clinical practice:consensus statement from the European advisory panel for tazarotene (Zorac TM). Dermatology (Basel, Switzerland) [serial online].1999;199(1):40-46.
[56]张江安.他扎罗汀(乙炔维甲酸)的研究进展[J].中国皮肤性病学杂志,2001,15(3)：200-201
[57]Dulvic M, Nagpal S, Asane AT, et al. Molecular mechanisms of tazarotene action in psoriasis. [J]. J Am Acad Dermatol,1997,37(2 Pt 3):S18-24.
[58]Mark R. Pharmacokinetics and safety review of tazarotene [J].Am Aced Dermatol,1998,39(4):134-138.
[59]Luo S, Zheng Y, Peng Z, et al. Effects of narrow-band ultraviolet B and tazarotene therapy on keratinocyte proliferation and TIG3 expression. The Journal Of Dermatology [serial online]. October 2008;35(10):651-657.
[60]Behrens S,Grundmann-Kollmann M,Schiener R,et al.Combination phototherapy of psoriasis with narrow-band UVB irradiation and topical tazarotene gel[J].J Am Acad Dermatol,2000,42(3):493-495.
[61]Koo J,Lowe NJ, Lew-Kaya D,et al.Tazarotene plus UVB phototherapy in the treatment of psoriasis[J].J Am Acad Dermatol,2000,43(11):821-828.
[62]Creamer,D,Allen,M.H,Sousa,A.et al.Localization of endothelial proliferation and microvascular expansion in active plaque psoriasis[J],Br J Dermatol,1997,136,859-865.
[63]Brody,I.Dermal epidemal involvment in the evolution of acute eruptive guttate psoriasis vulgaris[J].1984,82(5):465-470.
[64]潘卫利,吴绍熙。银屑病与微循环[J].国外医学皮肤病学分册,1989,001(01)：6-9.
[1]Rajadhyaksha M, Grossman M, Esterowitz D, et al. In vivo confocal scanning laser microscopy of human skin:melan in provides strong contrast[J].Invest Dermatol,1995,104(6):46-952.
[2]Nieholas AsPres, Ian, Egerton, Adrian C Lim, et al. Imaging the skin.Australasian[J]. Dermatol,2003,44:19-27.
[3].刘华绪,郑志忠,任秋实.基于光学共聚焦原理的皮肤在体三维成像系统及应用.[J]中华皮肤科杂志,2006,39：616-619.
[4]Alvarez-Roman R, NaikA, KaliaYN, et al.Visualization of skin Penetration using Confocal laser scanning microscopy. [J].European Journal of Pharmaceytics And Viopharmaceutics.2004,58(2):301-316.
[5]Girkin J.M, McConnell G.Advances in laser sources for confocal and multiphoton microscopy. [J] Microsc Res Tech,2005,67(1):8-14.
[6]Calzavara-Pinton, P; Longo, C; Venturini, M, et al..Reflectance Confocal Microscopy for In Vivo Skin Imaging. [J] Photochemistry and Photobiology,2008, 84(6):1421-1430.
[7]Langley RG, Rajadhyaksha M, Dwyer PJ, et al. Confocal scanning laser mi croscopy of benign and malignant melanocytic skin lesions in vivo[J]. J Am Acad Dermatol,2001,45(3):365-376.
[8]Giovanni Pellacani, Pascale Guitera, Caterina Longo, et al. The Impact of In Vivo Reflectance Confocal Microscopy for the Diagnostic Accuracy of Melanoma and Equivocal Melanocytic Lesions.[J]Journal of Investigative Dermatology.2007,127: 2759-2765.
[9]Pascale Guiteral, Giovanni Pellacani, Caterina Longo,et al. In Vivo Reflectance Confocal Microscopy Enhances Secondary Evaluation of Melanocytic Lesions.[J] Journal of Investigative Dermatology.2009,129(1):131-138;
[10]LangleyRG, Rajadhyaksha M, Dwyer PJ, Sober AJ, Flotte TJ, Anderson RR.Confocal scanning laser microscopy of benign and malignant melanocytic skin lesions in vivo.[J] J Am Acad Dermatol.2001,45(3):365-376.
[11]V. Ahlgrimm-Siess, C. Massone, S. Koller, R.et al.In vivo confocal scanning laser microscopy of common naevi with globular, homogeneous and reticular pattern in dermoscopy[J]British Journal of Dermatology 2008 158(5):1000-1007.
[12]Fain PR, Babu SR, Bennett DC, Spritz RA. HLA class Ⅱ haplotype DRB1*04-DQB1*0301 contributes to risk of familial generalized vitiligo and early disease onset.[J]Pigment Cell Res.2006;19(1):51-57.
[13]M Ardigo, I Malizewsky, ML Dell'Anna, E Berardesca, M Picardo.Preliminary evaluation of vitiligo using in vivo reflectance confocal microscopy[J]. JEADV. 2007,21:1344-1350.
[14]Gonzalez S, Tannous Z.et al. Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma. [J]J Am Acad Dermatol 2002;47(6):869-74.
[15]Marra, DE; Torres, A; Schanbacher, CF, et al.Detection of Residual Basal Cell Carcinoma by In Vivo Confocal Microscopy.[J]Dermatol Surg 2005;31(5):538-541.
[16]Stockfleth E, Kerl H. Guidline Subcommittee of the European Dermatology Forum. Guidlines for the management of actinic keratoses. Eur J Dermatol 2006; 16:599-606.
[17]Braakhuis BJ, Tabor MP, Kummer JA et al. A genetic explanation of Slaughter's concept of field cancerization:evidence and clinical implications[J]. Cancer Res. 2003,63(8):1727-1730.
[18]Aghassi D, Anderson RR, Gonzalez S.et al. Confocal laser microscopic imaging of actinic keratoses in vivo:a preliminary report[J]. J Am Acad Dermatol 2000, 43(1):42-48。
[19]Martina U, MD, Adrienne M, Francisca R, PHD.et al. Clinical Applicability of in vivo Reflectance Confocal Microscopy for the Diagnosis of Actinic Keratoses [J],Dermatol Surg,2008,34(5):610-619.
[20].赵辨.临床皮肤病学[M].第3版.南京：江苏科学技术出版社.2001.599-601.
[21]Hicks SP, Swindells KJ, Middelkamp-Hup MA, et al. Confocal histopathology of irrirant contact derm atitis in vivo and the impact of skin color (black vs white). [J] Am Acad Dermatol.2003,48(5):727-734.
[22]Maritza A. Middelkamp-Hup, H.-Y. Park,et al.Detection of UV-Induced Pigmentary and Epidermal Changes Over Time Using In Vivo Reflectance Confocal Microscopy[J]. Journal of Investigative Dermatology (2006) 126(2):402-407。
[23]Busam KJ,Hester K,Charles C, et al. Detection of clinically amelanotic malignant melanoma and assessment of its margins by in vivo confocal scanning laser microscopy[J]. Arch Dermatol,2001,137(7):923-929.
[24]Tannous Z,Torres A,Gonzalez S, et al.In vivo real-time confocal reflectance microscopy:a noninvasive guide for Mohs micrographic surgery facilitated by aluminum chloride, an excellent contrast enhancer[J]. Dermatol Surg,2003.29(8): 839-846.
[25].Curiel-Lewandrowski C, Williams CM, Swindells KJ.Use of in vivo confocal microscopy in malignant melanoma:an aid in diagnosis and assessment of surgical and nonsurgical therapeutic approaches [J].Arch Dermatol.2004,140(9):1127-1132.
[26]Gonzalez S, Rajadhyaksha M, Rubinstein G, et al. Characterization of psoriasis in vivo by reflectance confocal microscopy[J]. J Med,1999,30(5-6):337-356.
[27]Callen JP. Cutaneous lupus erythematosus:a personal approach to management[J]. Australas J Dermatol 2006; 47(1):13-27.
[28]. Jaworsky C. Connective tissue diseases. Lupus erythematosus. In:Lever's Histopathology of the Skin (Elder DE, Elenitzas R, Johnson BL,Murphy GF, eds),9th edn. Philadelphia:Lippincott Williams & Wilkins,2005; 293-305
[29]. M. Ardigo', I. Maliszewski, C. Cota, A.et al.Preliminary evaluation of in vivo reflectance confocal microscopy features of discoid lupus erythematosus[J].British Journal of Dermatology 2007,156(6):1196-1203
[30]Bystryn JC, Rudolph J. Pemphigus[J]. Lancet 2005; 366(9479):61-73.
[31]Amagai M, Klaus-Kovtun V, Stanley JR. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion [J].Cell 1991; 67(5):869-877.
[32]I. Angelova-Fischer, T. Pfeuti, D. Zillikensl and C. Rose.In vivo confocal laser scanning microscopy for non-invasive diagnosis of pemphigus foliaceus[J].Skin Research and Technology 2009; 15(1):40-44
[33]Ken-ichiro O'goshi, Christian Suihko,JΦrgen Serup.In vivo imaging of Intradermal tattoos by confocal scanning laser microscopy[J] Skin Research and Technology 2006; 12(2):94-98.
[34]Gonzalez S, Rajadhyaksha M, Gonzalez-Serva A, White WM, Anderson RR. Confocal reflectance imaging of folliculitis in vivo; correlation with routine histology [J]. Cut Pathol 1999;26(4):201-205.
[35]Martin J. Gruber, Alexandra Wackernagel, Erika Richtig, et al.Digital image enhancement for in vivo laser scanning microscopy[J]. Skin Research and Technology 2005; 11(4):248-253.