【作者】 黄洋；

【导师】 夏建新；

【作者基本信息】 吉林大学 ， 皮肤病与性病学（专业学位）， 2016， 硕士

【摘要】 蕈样肉芽肿是一种皮肤T细胞淋巴瘤,属于惰性肿瘤,进展较慢,在红斑及斑块期不提倡过度积极治疗,而到肿瘤期,特别是侵犯骨髓及周身系统必须进行化疗。治疗蕈样肉芽肿的方法有很多,包括阿维A,干扰素α、β,光疗,细胞毒性药物等,究竟效果如何?尚缺乏系统研究。本文针对8例蕈样肉芽肿患者采用阿维A联合干扰素α及光疗治疗,取得了较好的效果,并探讨其作用机制。目的:探讨阿维A联合干扰素α及光疗对蕈样肉芽肿的临床疗效及可能作用机制。方法:1.选取临床及病理及免疫病理诊断蕈样肉芽肿患者8例,8例患者均经组织病理及免疫组织化学证实。组织病理:均表现为真皮浅层密集淋巴样细胞浸润,部分病例细胞核呈脑回状;部分见亲表皮现象及Pautrier微脓肿;部分见淋巴细胞沿基底细胞呈线状排列;部分病例见到异形淋巴细胞。免疫组织化学:浸润淋巴细胞均强阳性表达CD3,不表达CD20,部分表达CD4和/或CD8,Ki67表达在5%左右。其中红斑期5例,斑块期2例,肿瘤期1例。给予口服阿维A,每日20mg;肌注干扰素α100万u,每日或隔日一次肌注;NB-UVB照射,最初剂量0.2 J,每周2次或隔日一次照射。2.体外培养人淋巴瘤细胞株HUT78,用干扰素α浓度分别为5000u/L、10000u/L、20000 u/L,阿维A浓度分别为0.1umol/L﹑1.0umol/L﹑10umol/L,以及联合应用阿维A浓度为0.5umol/L,干扰素α浓度分别为2500u/L、10000u/L进行干预,观察培养上清24h、48h、72h细胞因子IL-5、6、7、13的改变。结果:1)8例蕈样肉芽肿患者治愈4例,缓解4例,治疗时间1个月-1年;2)有2例患者临床缓解后停药3-5个月复发;3)体外实验研究结果显示,IL-5表达水平在联合组药物处理72h后,较对照组降低(p<0.01);4)IL-6表达水平在干扰素组,在相同的作用时间条件下,随药物浓度增加表达增高,存在剂量效应;在相同的浓度作用条件下,随药物处理时间延长表达增高,存在时间反应关系;在联合组药物处理24h、48h、72h后,基本上较对照组表达增高(p<0.01);5)IL-7表达水平在阿维A组(p<0.01)、干扰素组(p<0.01)和联合组(p<0.01)在药物处理24h后,均有一过性增高;48h、72h回复到正常表达水平;6)IL-13表达水平与对照组相比未见明显差异。结论:1)阿维A联合干扰素α及光疗对三期蕈样肉芽肿患者均安全、有效,提倡推广应用;2)蕈样肉芽肿患者需长期维持治疗,停药后复发率较高;3)其作用机制可能与阿维A和干扰素下调IL-5、上调IL-6、一过性上调IL-7的表达有关。更多还原

【Abstract】 Mycosis fungoides(MF) belongs to cutaneous T cell lymphoma, which is indolent and has a chronic clinical course. Over-treatment is not suitable for cases in erythema or plaque stage, but chemotherapy is required if the case progresses to tumor stage, especially with bone marrow or systems involvement. There are various treatments for MF, including acitretin, interferon α or β, phototherapy, cytotoxic drugs and so on, but the effectiveness of treatments is still lacking in systematic research. We had obtained a favourable effect of acitretin conbined with interferon α and phototherapy in 8 patients with MF, and sought to investigate the possible mechanism involved.Objective:Exploring the effect and mechanism of acitretin conbined with interferon α and phototherapy for mycosis fungoides.Methods: 1. 8 patients with MF were included who were confirmed by pathology and immunopathology, which included 5 cases in erythema stage, 2 cases in plaque stage and 1 cases in tumor stage. Histopathologic examination revealed infiltration of diffuse lymphoid cells in the upper dermis. Some cases were characterized by lymphocytes with cerebriform nuclei, presence of epidermal Pautrier’s micro abscesses, the band-like lymphocyte infiltration in the upper dermis close to basal cell or atypical lymphocytes. Immunohistochemical stains indicated tumor cells showed strongly positive for CD3, partly positive for CD4 and CD8, 5 percent positive for Ki67, but negative for CD20. The patients were treated by taking acitretin( 20 mg, po. qd), interferon α(1000000U, im. qd or qod), and NB-UVB irradiation(0.2J, qod or tiw). 2. Human lymphoma cell strains of HUT78 were established and cultured in vitro, intervened with interferon α(concentrations of 5000, 10000, 20000u/L), acitretin(concentrations of 0.1, 1.0, 10umol/L),or acitretin(concentrations of 0.5umol/L) combined with interferon α(concentrations of 25000, 10000 u/L) for 24, 48 and72 hours, and the levels of IL-5、6、7、13 were observed.Results: 1) 4 cases were cured and 4 cases were remission among the 8 cases of MF, courses of treatment lasted from 1 months to 1 year;2)2 of clinical remission cases recurred after suspension of the drug for 3-5months; 3) In vitro experiment, compared with control group, the expression level of IL-5 was reduced after 72 hours in conbined group(p<0.01); 4) In interferon treatment group, with the same application time interferon could induce increased expression of IL-6 exhibiting dose-effect; with the same dose treatment,the expression of IL-6 was increased exhibiting time response; and in conbined treatment group, with the same exposure time(24, 48,or 72h), the expression of IL-6 were gradually increased compared with control group; 5) In acitretin(p<0.01), interferon(p<0.01),and conbined treatment group(p<0.01), the expression level of IL-7 showed temporary upregulation within 24 hours, but returned to normal level after 48 hours or 72 hours exposure. 6) Compared with control group, the expression level of IL-13 was not different.Conclusions:1) The treatment of acitretin conbined with interferon α and phototherapy was proved safe and efficacious for all stages of MF patients, which is recommendable for clinical popularization and application; 2) MF patients need long-term maintenance therapy and it was extremely easy to relapse after withdrawal of drugs; 3) The decreased expression of IL-5, increased expression of IL-6 and transient increased expression of IL-7 may be the possible mechanism of the therapeutic effect of acitretin and interferon on MF.更多还原