尖锐湿疣患者HPV感染与细胞免疫功能的相关性

目的研究尖锐湿疣初发、复发患者之间,以及不同病程患者之间T淋巴细胞亚群的表达情况。方法选择56例尖锐湿疣患者,经冷冻治疗后至疣体消失后随访3个月,未复发者计入A组(20例),再次复发者计入B组(36例),应用三色荧光抗体染色法检测各组患者外周血CD4+,CD8+T淋巴细胞的表达,比较A,B两组CD4+,CD8+T细胞百分率及CD4+/CD8+比值的差异,并与正常对照组进行比较。同时根据病程长短,病程<3个月者计入C组(37例),病程≥3个月者计入D组(19例),比较C,D两组CD4+,CD8+T细胞百分率及CD4+/CD8+比值的差异,并与正常对照组进行比较。结果①初发及复发患者组T淋巴细胞亚群的变化:A组CD4+,CD8+T细胞百分率及CD4+/CD8+比值分别为(34.61±4.98)%,(29.46±4.56)%和(1.20±0.22),B组分别为(30.33±4.84)%,(33.10±5.90)%和(0.94±0.21),正常对照组分别为(39.58±4.31)%,(25.44±3.54)%和(1.57±0.17),与正常对照组相比,A,B两组CD4+细胞百分率及CD4+/CD8+比值明显降低,CD8+T细胞百分率明显升高,差异有统计学意义(P<0.05),且B组变化更为明显,与A组差异有统计学意义(P<0.05);②不同病程患者组T淋巴细胞亚群的变化:C组CD4+,CD8+T细胞百分率及CD4+/CD8+比值分别为(33.03±4.51)%,(30.60±5.36)%和(1.11±0.23),D组分别为(29.57±5.98)%,(34.12±5.73)%和(0.89±0.22),C,D两组与正常对照组相比,CD4+细胞百分率及CD4+/CD8+比值明显降低,CD8+T细胞百分率明显升高,差异有统计学意义(P<0.01),且D组变化更为明显,与C组差异有统计学意义(P<0.05)。结论与正常对照组比较,尖锐湿疣患者存在细胞免疫功能降低,且随着病程延长、病情反复,全身细胞免疫功能降低更为明显,导致CA迁延不愈。     

尖锐湿疣亚临床感染转归与局部T淋巴细胞亚群检测北大核心CSCD

目的研究尖锐湿疣亚临床感染(SPI)转归与局部T淋巴细胞亚群变化的关系,进一步探讨SPI转归机制。方法对确诊的SPI患者进行:①所有患者随访8个月,每月观察1次,以临床表现和醋酸白试验判定SPI三种转归结局:发展为典型CA,SPI持续存在、SPI消失,依次分为A组、B组、C组;②免疫组织化学方法检测皮损组织和正常对照组织的T细胞亚群(CD_4^+,CD_8^+,CD_4^+/CD_8^+)的百分比,分析局部细胞免疫功能与三种转归结局的相关性。结果与正常组比较,SPI组CD_4^+细胞、CD_8^+细胞、CD_4^+/CD_8^+比值差异均有统计学意义(P<0.05)。SPI转归组中,A组与B组CD_4^+/CD_8^+比值差异无统计学意义(P>0.05),A组、B组分别与C组比较CD_4^+/CD_8^+比值差异均有统计学意义(P<0.05)。结论 SPI患者存在局部细胞免疫功能降低,局部细胞免疫功能强弱是决定SPI临床症状及转归的重要因素之一。     

尖锐湿疣患者外周血及皮损T淋巴细胞亚群的检测

目的:了解尖锐湿疣(CA)患者系统和局部皮损细胞免疫功能的变化,以探讨细胞免疫功能对CA复发的影响。方法:通过流式细胞仪对21例初发CA患者、18例复发CA患者及23名正常人外周血进行T淋巴细胞亚群的检测,同时采用免疫组化染色方法对皮损进行CD4+/CD8+淋巴细胞染色,高倍显微镜下观察阳性细胞的数目。结果:初发CA和复发CA两组CD4+与CD8+细胞比值(1.04±0.50和1.01±0.59)均明显低于正常对照组(1.51±0.66,P<0.05),而两组间差异无显著性(P>0.05)。与正常对照组相比,两组CA局部皮损CD4+/CD8+比值(0.87±0.75和1.51±0.96)均明显降低(P<0.05),且复发CA组CD4+/CD8+比值也明显低于初发CA组,差异有显著性(P<0.05)。男女性患者不同部位皮损CD4+/CD8+比值均低于正常对照组,差异有显著性(P<0.05)。结论:CA患者存在全身和局部的细胞免疫功能低下,特别是局部细胞免疫功能低下在CA的复发中起着一定的作用。     

卡介菌多糖核酸对白癜风免疫调节作用及疗效的研究

目的探讨卡介菌多糖核酸(BCG-PSN)对白癜风的免疫调节作用及疗效。方法分别用流式细胞术和ELISA方法检测卡介菌多糖核酸治疗白癜风前后患者外周血T细胞亚群、IL-6和IFN-γ的水平。结果白癜风患者治疗前外周血CD4+百分比及CD4+/CD8+比值下降,CD8+百分比升高,IFN-γ水平降低。卡介菌多糖核酸治疗后,患者CD4+百分比及CD4+/CD8+比值较治疗前升高,CD 8+百分比降低,IFN-γ水平升高(P<0.05),IL-6水平无变化(P>0.05)。治疗组有效率为68.42%,对照组有效率31.58%,两组疗效差异有显著性(P<0.05)。结论卡介菌多糖核酸治疗白癜风可以显著改善患者的细胞免疫功能,提高其治疗有效率。     

尖锐湿疣亚临床感染转归与局部T淋巴细胞亚群检测

目的研究尖锐湿疣亚临床感染(SPI)转归与局部T淋巴细胞亚群变化的关系,进一步探讨SPI转归机制。方法对确诊的SPI患者进行:①所有患者随访8个月,每月观察1次,以临床表现和醋酸白试验判定SPI三种转归结局:发展为典型CA,SPI持续存在、SPI消失,依次分为A组、B组、C组;②免疫组织化学方法检测皮损组织和正常对照组织的T细胞亚群(CD_4~+,CD_8~+,CD_4~+/CD_8~+)的百分比,分析局部细胞免疫功能与三种转归结局的相关性。结果与正常组比较,SPI组CD_4~+细胞、CD_8~+细胞、CD_4~+/CD_8~+比值差异均有统计学意义(P0.05)。SPI转归组中,A组与B组CD_4~+/CD_8~+比值差异无统计学意义(P0.05),A组、B组分别与C组比较CD_4~+/CD_8~+比值差异均有统计学意义(P0.05)。结论 SPI患者存在局部细胞免疫功能降低,局部细胞免疫功能强弱是决定SPI临床症状及转归的重要因素之一。     

不同病程尖锐湿疣患者HPV感染与T细胞亚群表达情况的关系

目的探讨不同病程尖锐湿疣(CA)患者人乳头状瘤病毒(HPV)感染与T细胞亚群表达情况的关系。方法选择2012年1月—2015年2月我院收治的151例CA患者,根据病程长短分为A、B组,A组病程≤3个月,B组病程3个月,A组97例,B组54例,另选同期体检健康的51例作为对照组。采集3组患者外周血,并使用流式细胞术检测T淋巴细胞亚群的表达情况。取脱落疣体细胞,并使用核酸快速杂交分型法检测HPV-DNA。结果 B组患者CD4~+、CD4~+/CD8~+水平显著低于A组和对照组,CD8~+水平显著高于对照组及A组患者,差异均有统计学意义(P0.05)。HPV阳性患者151例,其中包括单纯HPV6/11~+、HPV16/18~+型感染各45例、49例,HPV6/11、16/18~+混合型感染57例。HPV6/11~+、HPV16/18~+、(HPV6/11~+、16/18~+)各组患者CD3~+、CD4~+、CD4~+/CD8~+水平均低于健康组,差异有统计学意义(P0.05);而3组间CD3~+、CD4~+、CD8~+、CD4~+/CD8~+水平比较,差异均无统计学意义(P0.05)。结论病程3个月以上CA患者细胞免疫功能明显降低,且各型HPV感染患者细胞免疫功能差异无统计学意义。     

间歇性应用免疫调节剂对亚临床型生殖器疱疹患者外周血淋巴细胞的影响

目的探讨影响亚临床型生殖器疱疹患者机体免疫水平的相关因素,以及予免疫调节剂治疗后机体免疫状态的改善情况。方法用荧光定量PCR检测患者带毒情况,用流式细胞仪检测患者的免疫功能。比较带毒阳性组与带毒阴性组,频发组(复发≥6次/年)与少发组(复发6次/年)以及使用免疫调节剂治疗前后患者的外周血淋巴细胞百分比。结果带毒阳性组CD3~+,CD4~+,CD4~+/CD8~+T细胞均低于带毒阴性组,差异有统计学意义(P0.05),频发组CD3~+,CD4~+,CD4~+/CD8~+,NK细胞均低于少发组,CD8~+T细胞高于少发组,差异有统计学意义(P0.05),治疗组CD3~+,CD4~+,CD4~+/CD8~+,NK细胞均低于对照组,CD8~+T细胞高于对照组,差异有统计学意义(P0.05),治疗后CD3~+,CD4~+,CD4~+/CD8~+,NK细胞均高于治疗前,CD8~+T细胞低于治疗前,差异有统计学意义(P0.05),在各种分组情况下比较B细胞数值变化,差异无统计学意义(P0.05)。结论亚临床型GH患者存在免疫功能低下的情况,带毒及频发患者的免疫抑制更为严重,而给予联合应用免疫调节剂后免疫低下较前改善。     

电灼结合中药内服外洗治疗尖锐湿疣的疗效观察

目的观察电灼结合中药内服外洗治疗尖锐湿疣的临床疗效及对患者T淋巴细胞亚群的影响。方法选择从2013年7月至2017年11月山西医科大学附属大同市第三人民医院泌尿外科治疗尖锐湿疣的患者148例,随机分成对照组和观察组两组,每组74例。对照组患者单独采用电灼治疗;观察组患者在采用电灼基础上结合中药内服外洗共同治疗。结果观察组尖锐湿疣患者复发率为10.8%,低于对照组尖锐湿疣患者复发率28.4%,差异具有统计学意义。(P<0.01)。两组治疗后复发组CD3+细胞、CD4+细胞水平、CD4+/CD8+细胞比值较未复发组低,而CD8+细胞水平较未复发组高,差异具有统计学意义。(P<0.05)。治疗后,观察组尖锐湿疣患者CD3+水平、CD4+水平、CD4+/CD8+比值高于对照组尖锐湿疣患者,且观察组尖锐湿疣患者CD8+水平低于对照组尖锐湿疣患者CD8+水平,差异具有统计学意义(P<0.01)。结论电灼结合中药内服外洗能减少尖锐湿疣的复发率。在临床治疗中,监测尖锐湿疣患者外周血T淋巴细胞亚群,对尖锐湿疣患者治疗后的复发预估及相应增强免疫治疗具有重要的指导意义。     

尖锐湿疣患者外周血T细胞亚群及乌体林斯疗效的研究

应用流式细胞仪检测60例CA患者外周血T细胞亚群,观察两组治疗前后外周血T细胞亚群变化及CA复发情况。激光去除疣体后给予乌体林斯肌注为CA实验组(I组),CA对照组(II组)给予白介素-2肌注,CA患者与正常对照组比较CD4+、CD4+CD8+明显降低(P<0.01),CD8+明显升高(P<0.01);I组治疗后CD3+无明显变化,CD4+、CD4+CD8+明显升高(P<0.01),CD8+明显下降(P<0.01)。I组与II组治疗后I组CA患者CD4+及CD4+CD8+均较II组升高(P<0.05),CD8+无明显差异;随访3个月,I组的复发率低于II组复发率(P<0.05);未复发的45例和复发的15例上述指标无明显变化(P>0.05)。     

卡介菌多糖核酸联合咪喹莫特对尖锐湿疣CO_2激光术后免疫功能的影响

目的:探讨卡介菌多糖核酸联合咪喹莫特对尖锐湿疣CO_2激光术后免疫功能的影响。方法:选择120例初发的尖锐湿疣患者为研究对象,分为A组和B组,两组患者均行CO_2激光术,术后,A组患者给予5%咪喹莫特乳膏,B组患者给予卡介菌多糖核酸~+5%咪喹莫特乳膏,比较两组患者治疗后免疫功能及临床疗效,选择同期40例健康查体者为对照组。结果:A组和B组治疗前CD3~+、CD4~+、CD4~+/CD8~+和NK细胞的百分比、IFN-γ和IL-12水平均明显低于健康对照组(P0.05),CD8~+和IL-4的水平高于健康对照组(P0.05),治疗后,A组和B组CD3~+、CD4~+、CD4~+/CD8~+和NK细胞的百分比、IFN-γ和IL-12水平均明显升高,CD8~+和IL-4的水平均明显降低,且B组改善的程度优于A组,差异具有统计学意义(P0.05)。A组治愈率明显低于B组治愈率(χ2=8.00,P=0.008),复发率高于B组的复发率(χ2=5.926,P=0.029)。结论:卡介菌多糖核酸联合咪喹莫特乳膏治疗能明显改善尖锐湿疣CO_2激光术后患者免疫功能,提高治疗有效率,降低尖锐湿疣的复发。     

阿维A长期治疗儿童板层状鱼鳞病1例

回顾性分析1例板层状鱼鳞病儿童服用阿维A后皮损改善情况。患者初始口服阿维A 5mg/d治疗半年效果不明显,后加量至10mg/d,2周后疗效明显,黏着性鳞屑基本脱落。患儿口服阿维A已超过7年,暂未见明显生长发育迟缓。     

Acitretin versus etretinate in psoriasis. Clinical and pharmacokinetic results of a German multicenter study

175 patients with severe psoriasis of different types were treated with 10, 25, or 50 mg acitretin and compared with patients receiving 50 mg etretinate over a period of 8 weeks in a randomized, double-blind multicenter study in the Federal Republic of Germany. Plasma concentrations of etretinate and its metabolite acitretin were measured during therapy and also 3 weeks after cessation of treatment. After 4 weeks of treatment, a trend toward clinical improvement was shown in all groups with increasing dosage. Those groups receiving the lower acitretin doses (i.e., 10 and 25 mg/day) had more dropouts than the groups taking 50 mg acitretin or 50 mg etretinate. Complete remissions before the end of therapy occurred only among those receiving higher doses. Enlargement of psoriatic lesions, however, could be observed during treatment with both retinoids, despite improvement of other parameters, as measured by psoriasis area and severity index (PASI) and psoriasis severity index (PSI). After 8 weeks, a significant improvement was calculated by the PASI score and by a newly defined, corrected PASI score for all four dose regimens compared with baseline levels. A greater than 50% PSI score improvement was seen in 50% of patients treated with 10 mg acitretin, 40.5% with 25 mg acitretin, 53.8% with 50 mg acitretin, and 61.1% with 50 mg etretinate. No statistical differences were found among these groups at any time during the 8-week period. No new or unexpected side effects occurred during acitretin treatment. Moreover, cholesterol levels did not significantly change. Three weeks after cessation of drug administration, the plasma concentrations of acitretin were below the sensitivity level of the assay, whereas etretinate was still quantifiable. It is interesting that acitretin plasma concentrations during therapy with 50 mg acitretin were markedly lower (means = 18 ng/ml) than were acitretin levels during treatment with 50 mg etretinate (means = 36 ng/ml).     

Acitretin for lichen amyloidosus

We present two cases of lichen amyloidosus treated with retinoids. A 57-year-old Vietnamese woman has had extensive generalized recalcitrant lichen amyloidosus for 23 years. Treatment with oral etretinate (25 mg/day) for 3 years, and later oral acitretin (10 mg/day) for the past 10 years, has controlled the pruritus and flattened the hyperkeratotic papules. Whenever the acitretin was ceased her symptoms flared within weeks. On each occasion reintroduction of acitretin was effective within 1-2 months. The second case is that of a 51-year-old Australian Aboriginal woman who had a 2-year history of lichen amyloidosus affecting her lower legs. A 2-month course of oral acitretin (25 mg b.d.) produced a marked improvement in both the pruritus and hyperkeratotic papules. She was then lost to follow up for 2 years, during which time her symptoms recurred.     

Epidermodysplasia verruciformis with multiple mucosal carcinomas treated with pegylated interferon alfa and acitretin

Epidermodysplasia verruciformis (EV) is characterized by abnormal genetically-determined susceptibility to widespread and persistent infection of the skin with human papillomaviruses (HPV). The infection results in disseminated pityriasis versicolor-like lesions and flat warts. Skin malignant changes are very common and occur on sun-exposed areas. Several treatments have been used but without consistent benefit. Recently, retinoids and alpha-interferon, alone or in combination, have been reported to be of value in the therapy of EV lesions. We present the case of a 43-year-old white female affected by EV who developed multiple squamous cell carcinomas in the oral and genital mucosae during the previous four years. Both wart and cancer lesions harbored HPV24 along with the novel putative HPV type FA51. The patient was treated with a combination of acitretin (0.2 mg/kg per day) and peginterferon alfa-2b (1 microg/kg per week s.c.) for one year, with marked improvement of verrucous lesions and no recurrence of mucosal cancer. Thereafter, interferon was stopped whereas acitretin therapy was continued, but a new Bowen's disease developed in the perianal region, and the acitretin dose was increased at 0.5 mg/kg per day. At six-month follow-up, only a low number of flat warts persisted, and no clinical signs of cutaneous or mucosal carcinoma were evident.     

Combination therapy with acitretin and glycyrrhizin in generalized pustular psoriasis with liver test abnormalities: A case series

Liver test abnormalities (LTA) are a frequent extracutaneous manifestation in generalized pustular psoriasis (GPP). Due to possible hepatotoxicity of systemic monotherapy, it is challenging to simultaneously achieve clinical remission and LTA normalization. However, evidence for therapy is lacking. The aim of this study was to assess the effectiveness of combination therapy of acitretin and glycyrrhizin in nine GPP patients with LTA. During the acute phase of GPP, a combination of acitretin (0.5 mg/kg/d PO) and glycyrrhizin (80 mg/d intravenous) was initiated. After 2 weeks, all the patients promptly achieved at least 77% improvement in the severity score of GPP, as well as a significant reduction of liver enzymes. The patients were continuously treated with tapered doses of acitretin (20‐30 mg/d PO) and glycyrrhizin (150 mg/d PO), and presented stable conditions during the 12‐month follow‐up. In conclusion, we consider that the combination of acitretin plus glycyrrhizin is an effective and safe therapy in GPP patients with LTA.     

Cover Image,Volume 33, Issue 3

Most available options for the treatment of warts are limited by the potential for scarring, pain, lack of response, or recurrences, and the patients are often unable to tolerate and accept those experiences. The aim of this study was to evaluate the clinical efficacy and safety of oral systemic acitretin monotherapy in patients with extensive/recalcitrant cutaneous warts. The patients were given a dose of acitretin of 0.8 mg kg⁻¹ day⁻¹, and the clinical efficacy and safety of acitretin was assessed every 2 weeks for 2 months. A total of 14 patients (12 males and 2 females) were included, with an age of 14‐60 years (mean 33 ± 14.7 years) and a course of 4‐48 months (mean 21.6 ± 13.4 months). After 2 months of acitretin treatment, 42.9% (6/14) of patients (including warts of the feet, legs, and hands) exhibited complete response, 28.6% (4/14) excellent response, and 28.6% (4/14) good response. All patients demonstrated significant improvement, and the drug was well tolerated, with no patients discontinuing therapy due to side effects. Common mild side effects included dry skin and cheilitis. There were no recurrences during a follow‐up period of 6 months. Acitretin monotherapy is an effective, safe, and well‐tolerated treatment for patients with extensive/recalcitrant cutaneous warts who are unsuitable for or unwilling to accept traditional treatment methods.     

阿维A控制34例尖锐湿疣复发的疗效观察

目的观察口服阿维A治疗尖锐湿疣疗效。方法将62例尖锐湿疣患者随机分为两组，A组用二氧化碳激光清除瘤体后口服阿维A治疗，B组用二氧化碳激光清除瘤体。结果随访3月，A组29例，复发5例，复发率17．24％。B组26例，复发15例，复发率57．69％。结论阿维A治疗尖锐湿疣有显著疗效，并能减少其复发率。     

Epidermodysplasia verruciformis: association with isolated IgM deficiency and response to treatment with acitretin

We describe a 25-year-old woman, who had extensive, large viral warts consistent with epidermodysplasia verruciformis (EV) since she was 6-year-old. Laboratory studies revealed an isolated IgM-deficiency, but the patient demonstrated no other abnormalities. She was treated with oral acitretin (0.5-1 mg/kg/day) for six months and her skin lesions improved slightly. However, after discontinuing the treatment, the lesions came back but she declined further treatment.     

Cimetidine treatment for viral warts enhances IL-2 and IFN-gamma expression but not IL-18 expression in lesional skin

Cimetidine has been shown to improve various types of human neoplasms and more recently it has been shown to be effective in treating recalcitrant or multiple viral warts in some reports. However, it is not well understood why cimetidine is effective on those kinds of viral warts. We investigated 55 patients with multiple viral warts treated only with oral cimetidine for up to 4 months to examine the efficacy of treatment. The patients were divided into two groups: group A received oral cimetidine (<20 mg/kg/day) and group B received the drug (30 to 40 mg/kg/day). In addition, using real time PCR, we measured mRNA levels of the cytokines interleukin-2 (IL-2), IL-18, and interferon (IFN)-gamma taken from selected punch biopsy specimens before and during treatment. As a result, 34.5% (19/55) of the patients had a dramatic clinical improvement or complete remission (CR) of their viral warts and 23.6% (13/55) of the patients had partial responses (PR) within 4 months of cimetidine therapy. IL-2 and IFN-gamma mRNA levels were significantly increased and IL-18 mRNA levels were decreased in tissues of effectively treated viral warts. Our results show that the higher dose of oral cimetidine was more effective in treating multiple viral warts, that cimetidine activates Th1 cells to produce IL-2 and IFN-c and that their expression correlates with wart remission. These results suggest that cimetidine is an effective treatment for viral warts. In addition, based on the decrease in IL-18 mRNA elicited by the drug, IL-18 might be expressed by keratinocytes infected with HPV.     

Verrucae Treated by Levamisole

To assess the role of levamisole in treatment of different types of warts, a double-blind study was conducted on 40 patients with different types of warts. Patients were divided into two equal groups, A and B. Group A received levamisole 5 mg/kg body weight on 3 consecutive days every 2 weeks for a period up to 5 months, while patients of group B received placebo for the same period. In group A, 12 patients showed complete cure (60%), two showed partial cure (10%), and the remaining six patients showed no response (30%). In group B, complete cure was achieved only in one case. The higher cure rate was observed in plane and common warts, while plantar warts showed no improvement with levamisole treatment.