Aspects of Langerhans cells and TNF-α in the cutaneous immunity of anogenital warts

BackgroundAnogenital warts are the leading sexually transmitted infection in patients seeking care at specialized clinics. They may display a vast array of forms, according to the interaction of the virus with the host's immunity. Cellular immunity is the epithelium's main form of defense against the virus, involving an active participation of the Langerhans cells and pro-inflammatory cytokines such as TNF-α.ObjectiveTo assess the epithelial immune response of anogenital warts in males, according to the number of lesions presented.MethodsThis is a prospective, cross-sectional study carried out at the dermatology outpatient clinic in a tertiary hospital. We included male patients over 18 years of age without comorbidities who had anogenital condylomata and no previous treatments.In order to evaluate the local epithelial immunity, the lesions were quantified, then removed and employed in CD1a immunohistochemistry assays for assessing the morphometry and morphology of Langerhans cells; TNF-α; reaction was used for determining cytokine positivity in the epithelium.Results48 patients were included in the study. There was no statistically significant difference as to the number of Langerhans cells, in their morphology, or the presence of TNF-α. However, patients presenting with more Langerhans cells in the lesions had cells with a star-like and dendritic morphology, whereas in those with a lower cell count had cells with a rounded morphology and no dendrites (p < 0.001).Study limitationsSmall number of patients analyzed.ConclusionThere was no difference in epithelial immunity between patients having few or many anogenital condyloma lesions as measured by the morphology and morphometry of Langerhans cells and TNF-α; positivity. Such an assessment employing immunity markers differing from the usual ones is expected to yield useful results.     

冷冻疗法配合转移因子治疗尖锐湿疣效果观察

目的研究冷冻疗法配合转移因子治疗尖锐湿疣（CA）的效果，比较转移因子注射法和口服法的效果。方法对64例CA病人在冷冻治疗的基础上，予以局部并皮下注射转移因子（A组，32例）或口服转移因子胶囊（B组，32例）治疗。结果A组治愈30例，治愈率为93．8％；B组治愈27例，治愈率为84．3％，两组疗效比较差异无显著性（x^2=1．44，P〉0．05）。结论两种方法治疗CA均具良好效果。     

尖锐湿疣患者IL—2和IFN—r水平观察

目的对人乳头瘤病毒(HPV)感染所致尖锐湿疣患者的IL-2和IFN-r水平进行观察,探讨HPV感染对机体细胞因子的影响。方法该研究调查了30例经临床诊断的尖锐湿疣患者,并经HPV6.II型PCR检测为阳性,其中随机抽取了10例进行组织病理学诊断,诊断结果均为尖锐湿疣。30例患者为CA患者组,选择30例正常健康者作为对照组,采用夹心酶联免疫吸附法(ELISA)试剂盒对30例CA患者和30例对照组受试者的血清中白介素-2(IL-2),r干扰素(IPN-r)的含量进行检测。结果CA患者与正常对照组对比较血清中IL-2(17.75±7.52pg/ml,P<0.01)和IFN-r(27.89±9.1pg/ml,P<0.05)的含量显著性下降。结论HPV感染导致尖锐湿疣患者血清中IL-2,IFN-r含量显著性下降,引起细胞免疫功能下降,因此,在临床上可以考虑用白介素-2和r干扰素治疗尖锐湿疣。     

Time‐lapse imaging points towards a non‐toxic,mainly immune‐driven mode of action of ingenol mebutate in the treatment of anogenital warts

Recently, it has been reported that ingenol mebutate (IM) is an effective treatment option for anogenital warts (AGW), inducing fast wart necrosis within 24 hours in vivo. With regard to its mode of action, IM is thought to act both as an inducer of direct cytotoxic effects and immunologic mechanisms. To distinguish whether the wart necrosis is mainly caused by cytotoxic effects, or whether immune mechanisms are leading, we used time‐lapse imaging to analyse IM‐treated warts ex vivo over 24 hours. Ex vivo IM‐treated warts, which have been detached from the immune system, did not show destructive necrosis, pointing towards a primarily immune‐driven mode of action of IM in the treatment of AGW.     

尖锐湿疣皮损中Caspase 8与p-Akt的表达

目的 探讨Caspase 8与p-Akt在尖锐湿疣皮损中的表达及意义.方法 收集尖锐湿疣30例、宫颈癌20例、正常皮肤(包皮)20例,采用免疫组化检测以上组织中Caspase 8及p-Akt的表达及分布.结果 Caspase 8在尖锐湿疣皮损、宫颈癌、正常皮肤中阳性率分别为23.33%、80%、90%.Caspase 8在尖锐湿疣中的表达强度显著低于正常皮肤(P<0.01)和宫颈癌组织(P<0.001).p-Akt在尖锐湿疣皮损、宫颈癌组织、正常皮肤组织中的阳性率分别为93.33%、95%、90%.p-Akt在尖锐湿疣皮损的表达强度显著高于正常皮肤组织(P<0.001),低于宫颈癌组织(P<0.001).在尖锐湿疣皮损和正常皮肤组织中,Caspase 8与p-Akt的表达无相关性.在宫颈癌中,Caspase 8与p-Akt的表达存在显著的正相关(r=0.369,P<0.05).结论 Caspase 8的凋亡启动受抑制及p-Akt的抗凋亡作用可能参与了尖锐湿疣的发生发展.     

氨基酮戊酸-光动力疗法对尖锐湿疣组织中血管内皮生长因子和增殖细胞核抗原表达的影响

【摘要】 目的 研究氨基酮戊酸-光动力疗法（ALA-PDT）对尖锐湿疣组织中血管内皮生长因子（VEGF）和增殖细胞核抗原（PCNA）表达的影响。方法 2016年10月至2017年9月在郑州大学第一附属医院皮肤科门诊收集56例尖锐湿疣患者ALA-PDT治疗前及第1次治疗后1周皮损各1份，采用免疫组化SP法检测尖锐湿疣组织角质形成细胞中VEGF及PCNA的表达情况。分别采用χ2检验和秩和检验分析治疗前后VEGF与PCNA蛋白表达率和表达强度的差异，采用Spearman分析检验VEGF及PCNA蛋白表达的相关性。结果 ALA-PDT治疗前尖锐湿疣组织角质形成细胞中VEGF和PCNA表达率分别为71.43%（40/56）、73.21%（41/56），治疗后分别为44.64%（25/56）、41.07%（23/46）。治疗前后VEGF和PCNA的表达率（χ2值分别为8.25、11.81， 均P < 0.05）及表达强度（H值分别为11.29、12.22，均P < 0.05 ）差异均有统计学意义。ALA-PDT治疗前后尖锐湿疣组织VEGF与PCNA表达呈正相关（rs值分别为0.202、0.273，均P < 0.05）。结论 ALA-PDT治疗后尖锐湿疣组织中VEGF和PCNA表达下降，这可能是其治疗尖锐湿疣的作用机制之一。     

A Surgical Approach to Anogenital Buschke Loewenstein Tumours (Giant Condyloma Acuminata)

Background: Condyloma acuminata are anogenital warts caused by human papillomavirus (HPV). Neglected giant peri-anal condyloma acuminata (Buschke Loewenstein Tumours) require major surgical procedures. This report reflects our experience concerning the aggressive surgical approach to this rarely presented type of condyloma acuminata.

Methods: The medical records of five patients, who had been surgically treated following the diagnosis of giant perianal condyloma acuminata between April, 1996 and September, 2003 were reviewed and evaluated retrospectively. Full thickness tumour and skin excisions were performed followed by delayed split thickness skin graftings in all patients. Results: Five patients (3 men, 2 women) who suffered from giant condyloma acuminata lesions obliterating the anal canal were evaluated. The mean age was 36.5 years (range: 24–52). All patients underwent total surgical excisions. The wounds were left open for secondary healing, and following a mean time period of 35 days, split thickness skin graftings were performed. The histopathologic examinations of the specimens of these five patients did not reveal any malignant transformations. No recurrences were detected at the end of a mean follow-up period of 22 months and all patients were considered to be disease-free at the end of their long-term 5-year follow-up periods.

Conclusions: Peri-anal condyloma acuminatum is usually a benign disease, but may grow locally to an excessive extent, developing into a Buschke Loewenstein Tumour, and may cause serious peri-anal hygiene problems. Even though the incidence of malignant transformation is rare, there is always a risk of this complication occurring. Transmission of the disease to other sexual partners is another point of concern. Therefore, this disease must be treated aggressively with total surgical excision. The results of our surgical treatment methods are satisfactory.     

Preoperative Immune Status Determines Anal Condyloma Recurrence After Surgical Excision

PURPOSE: Immunosuppression is an important risk factor for anal condyloma progression; however, its effects on postoperative outcomes remain unclear. In the present study, we investigated risk factors and recurrence rates in immunocompromised patients requiring surgery for medically intractable anal condyloma. METHODS: A retrospective review was performed on 63 consecutive patients who underwent surgical intervention for medically intractable anal condyloma at a single institution. Patient cohorts included immunosuppressed patients (e.g., HIV-seropositive, leukemia, idiopathic lymphopenic syndrome, or transplant patients; n = 45) and immunocompetent patients (n = 18). Recurrence rates and time to recurrence after surgery were determined for both groups. Preoperative CD4 count and viral load within the HIV subpopulation were also determined. The majority of the patients were male (90 percent), with a median age of 36 years. RESULTS: Anal condyloma recurred in 66 percent of the immunosuppressed patients compared with 27 percent of the immunocompetent group. Recurrence time expressed in months was shorter in immunosuppressed patients than in immunocompetent patients (6.8 ± 1.5 vs. 15 ± 5.7 months; P < 0.05). In the subpopulation of HIV-seropositive patients, no association was found between recurrence rates and viral loads; however, CD4 counts were significantly lower in those who had recurrence than in those who did not (226 ± 31.7 vs. 401 ± 51.2 cells/l; P < 0.05). CONCLUSIONS: After surgery, anal condyloma in immunosuppressed patients recurs significantly more often and within a shorter period of time than in patients with a competent immune system. Additionally, in HIV-seropositive patients, CD4 counts should be maximized to prevent early recurrence of anal condyloma.     

重组人干扰素α2b喷雾剂的抗病毒药效评价及临床观察

目的研究重组人干扰素α2b喷雾剂抑制单纯疱疹病毒、流感病毒、SARS冠状病毒有效浓度范围,为临床研究提供依据并进行治疗病毒性皮肤疾病临床验证。方法采用细胞病变抑制法研究重组人干扰素a2b喷雾剂抑制单纯疱疹病毒HSV-1及HSV-2攻击Vero细胞,抑制流感甲型及乙型病毒攻击人胚肾细胞,抑制SARS冠状病毒攻击Vero细胞的体外抗病毒作用。采用多中心、随机双盲临床试验评价重组人干扰素α2b喷雾剂对流感甲型及乙型病毒、尖锐湿疣的治疗效果。结果重组人干扰素a2b喷雾剂抑制单纯疱疹病毒HSV-1及HSV-2对Vero细胞的攻击的半数有效浓度（IC50）分别为81．2IU／ml和390．0IU／ml;重组人干扰素α2b喷雾剂抑制流感甲型及乙型病毒对人胚肾细胞攻击的IC50分别为534．1IU／ml和3645．5IU／ml;抑制SARS冠状病毒对Vero细胞攻击的IC50为11．77IU／ml。多中心、随机、双盲的临床研究表明,重组人干扰素α2b喷雾剂治疗单纯疱疹的有效率为89．09％,治疗尖锐湿疣有效率为22．0％,治愈率为17．0％,患者均未见明显不良反应。结论体外实验表明重组人干扰素α2b喷雾剂对单纯疱疹病毒、流感病毒、SARS冠状病毒有显著抑制作用,临床研究表明重组人干扰素α2b喷雾剂作为蛋白经皮给药制剂可用于单纯疱疹和尖锐湿疣的临床治疗。     

二氧化碳激光联合光动力治疗男性尖锐湿疣的临床疗效观察

目的观察二氧化碳(CO2)激光联合光动力治疗男性尖锐湿疣的疗效。方法将46例初诊为男性尖锐湿疣患者随机分为两组,每组23例。两组均采用CO2激光一次性对疣体逐个气化烧灼,气化范围大于疣体周围2 mm,治疗组激光术后将氨基酮戊酸散配制成20%的浓度,敷于创面上,3 h后予艾拉光动力治疗,每周治疗1次,2~3次为一疗程。两组均于术后1、3、6个月随访。结果对照组与治疗组的治愈率分别为65.22%、91.30%,差异有统计学意义(χ2=4.60,P<0.05)。治疗后1、3个月两组复发率差异无统计学意义(P>0.05),而6个月时对照组复发率明显高于治疗组,差异有统计学意义(χ2=5.86,P<0.05)。结论 CO2激光联合光动力治疗男性尖锐湿疣疗效确切,复发率低,可在临床治疗中推广应用。