Immunotherapy of genital warts with inosine pranobex and conventional treatment: double blind placebo controlled study.

In a multicentre, prospective, randomised, placebo controlled study of 55 patients with histories of genital warts for at least one year, a four week course of inosine pranobex 3 g a day improved the clinical response to conventional treatment (primarily podophyllin or trichloroacetic (now called trichlorethanoic) acid). Although more patients given inosine pranobex improved than those given placebo, the difference in general response between the two groups was not significant. When other variables (numbers of warts and extent of lesions) were considered, however, the patients given inosine pranobex fared significantly better. These results suggest that inosine pranobex may be worth considering as adjunct to treatment of patients with refractory genital warts.     

Modern treatment of warts: cure rates at 3 and 6 months

Four-hundred consecutive referrals with viral warts of the hands and/or feet were investigated to determine the cure rate from a combination of cryotherapy, keratolytic wart paint and paring. For treatment failures after 3 months, the value of continuing cryotherapy and of additional treatment with the immunomodulator inosine pranobex were assessed. Subjects were treated for 3 months with wart paint and cryotherapy and were randomized to receive, or not, paring in addition. Those who did not respond by 3 months were randomized to receive, or not, 3 months further cryotherapy, and to receive inosine pranobex 60 mg/kg/day for 1 week each month, or matching placebo. Fifty-two per cent of subjects were cured by 3 months. The chance of cure was inversely related both to the length of history and to the diameter of the largest wart. Paring improved the cure rate for plantar warts but not for hand warts. During the second 3 months the cure rate fell to 41%. Neither cryotherapy nor inosine pranobex significantly improved this response.     

Suppression of frequently recurring genital herpes: acyclovir v inosine pranobex.

The suppressive action of acyclovir and inosine pranobex was compared in a randomised double blind controlled trial in patients with frequently recurring genital herpes. Fourteen patients received acyclovir and 17 inosine pranobex. Treatment continued for 12 weeks. The time to the first recurrence was significantly longer and the frequency of recurrences significantly less in the recipients of acyclovir. No important side effects were noted. It is concluded that acyclovir is the treatment of choice to suppress often recurring genital herpes.     

Human Papillomavirus

The monetary and personal costs to society of human papillomavirus (HPV) infection are enormous. In order to make a comparison of different treatment methods we reviewed the entire literature on HPV treatment from January 1966 to December 2003 using MEDLINE, with particular reference to published meta-analyses, randomized controlled and comparative studies. Patient-applied therapies offer patients the possibility of convenient and, on the whole, pain-free treatment. Podofilox (podophyllotoxin) and salicylic acid for genital and extragenital warts, respectively, have the additional advantage of being the most cost-effective treatments and, on this basis, they are to be commended as appropriate first-line agents. The second-line treatment of choice for common warts is cryotherapy. For recalcitrant common warts possible options include inosine pranobex with cryotherapy or electrosurgery, imiquimod with paring and occlusion, intralesional bleomycin, or diphencyprone. Alternative first-line and second-line treatments for genital warts would be either some form of surgical removal or imiquimod. The first option may be the cheapest but this has to be balanced against a degree of post-operative morbidity. Limited data from comparative studies do not show any clear difference in efficacy between cryotherapy, trichloroacetic acid, scissor excision, electrosurgery, and laser surgery in the treatment of genital warts, and the cost effectiveness of these therapies is probably similar to that of imiquimod. Cryotherapy and trichloroacetic acid are relatively expensive and inconvenient for patients and should be reserved as third-line treatments with certain exceptions, such as cryotherapy for meatal warts. The duration of treatment is significantly related to the number of warts present, the area covered by the warts, and the length of time the warts have been present. For recalcitrant anogenital warts third-line treatment options that show promise include surgery in combination with imiquimod or cidofovir cream. For squamous intraepithelial lesions that cannot easily be excised or physically ablated current treatment options include imiquimod and fluorouracil cream. The latter is an inexpensive option but causes the greatest morbidity. It is hoped that cidofovir may be added to this list if it becomes commercially available, and that protective and therapeutic HPV vaccines will transform the management of HPV in the future.     

Multicenter randomized study of inosine pranobex versus acyclovir in the treatment of recurrent herpes labialis and recurrent herpes genitalis in Chinese patients

The objective of the study is to evaluate the efficacy and safety of oral inosine pranobex as compared with acyclovir in the treatment of recurrent herpes labialis (RHL) and recurrent herpes genitalis (RHG). A multicenter double‐blind, double‐dummy, randomized, controlled, parallel group trial was conducted in 144 patients with RHL and 144 RHG. Patients were assigned to treatment in one of two groups: (i) inosine pranobex group (active inosine pranobex, 1 g four times daily, and acyclovir placebo); or (ii) acyclovir group (active acyclovir, 200 mg five times daily, and inosine pranobex placebo). The total symptom score (TSS) of patients with RHL did not differ in the inosine pranobex and acyclovir group on the 3rd or 7th day of treatment. There was also no difference in the efficacy rates between the two groups. No difference of TSS was observed between patients with RHG taking inosine pranobex and acyclovir on days 3 or 5 of the treatment, respectively. The short‐term clinical recurrence rate of RHG at 3‐month follow‐up was much lower in the inosine pranobex group than acyclovir group. The incidence of hyperuricemia was higher in the inosine pranobex group than acyclovir group. In conclusion, inosine pranobex was as effective as acyclovir in treating RHL and RHG with significantly greater reduction of the short‐term recurrence rate of herpes genitalis at 3‐month follow up. Long‐term recurrence rates at 6 months or longer remain to be determined. Hyperuricemia should be monitored during the treatment.     

Topical imiquimod 5% cream as an effective treatment for external genital and perianal warts in different patient populations

BACKGROUND: Genital infection with human papillomavirus, the cause of genital warts, is one of the most common sexually transmitted diseases. GOAL: The aim of this analysis was to determine whether patients' demographic variables affect the efficacy of imiquimod 5% cream versus vehicle cream for the treatment of external genital and perianal warts. STUDY DESIGN: Male and female immunocompetent patients applied imiquimod 5% cream topically to external genital warts 3 times a week until wart clearance or for up to 16 weeks. RESULTS: As previously published, the intent-to-treat (ITT) clearance rate was 50% (54/109) in the imiquimod-treated group and 11% (11/100) in the vehicle-treated group ( P< 0.0001). The ITT clearance rate in the imiquimod-treated group was higher in females (72%) than in males (33%). We have examined the clearance rates for subgroups based on variables of gender, baseline wart area, duration of current outbreak of warts, previous wart treatment, and tobacco use. For each of these subgroups, imiquimod was statistically more effective than vehicle in eradicating external genital and perianal warts. CONCLUSION: Imiquimod 5% cream is an effective treatment for external genital and perianal warts and provides a significant benefit in comparison with vehicle cream, independent of gender, initial wart size, duration of current outbreak of warts, previous wart treatment, or tobacco use.     

Treatment of alopecia totalis with a combination of inosine pranobex and diphencyprone compared to each treatment alone

Recent developments in alopecia areata have included the use of oral inosine pranobex and the introduction of diphencyprone as a contact sensitizer. Good results have been claimed for these treatments even in severe forms of the disease. We performed a study to investigate the efficacy of a combination of these treatments in the most severe form of alopecia areata. Thirty-three patients suffering from alopecia totalis were enrolled. Subjects were divided into three groups matched for age and sex. One group received treatment with inosine pranobex (50 mg/kg/day) for 6 months. The second was sensitized to diphencyprone and treated for 6 months by maintenance of contact allergic dermatitis on the scalp. The third received both treatments. There was no evidence of response to inosine pranobex in any of the 22 subjects who received this treatment. Only two of 22 patients responded to diphencyprone. Patients with long-standing alopecia totalis contemplating diphencyprone therapy should be advised that the chances of success are only around 10%. Inosine pranobex does not appear to improve the response rate.     

Treatment of external genital warts: a randomised clinical trial comparing podophyllin, cryotherapy, and electrodesiccation.

Four hundred and fifty patients were enrolled into a randomised clinical trial in a public sexually transmitted diseases clinic to evaluate the efficacy of podophyllin, cryotherapy, and electrodesiccation for treatment of external genital warts. Complete clearance of warts was observed in 41%, 79%, and 94% of patients who received up to six weekly treatments of podophyllin, cryotherapy, and electrodesiccation, respectively. Relapses occurred in 25% of all patients, yielding 3 month clearance rates of 17%, 55%, and 71% for podophyllin, cryotherapy, and electrodesiccation, respectively. Wart volume and duration did not influence treatment outcome. Response to therapy was greater in women than in men, and did not differ by treatment modality. Electrodesiccation and cryotherapy were more effective than podophyllin for the treatment of external genital warts, but none of these three treatments were highly successful.     

Complete remission of recalcitrant genital warts with a combination approach of surgical debulking and oral isotretinoin in a patient with systemic lupus erythematosus

Genital warts in immunocompromised patients can be extensive and recalcitrant to treatment. We report a case of recalcitrant genital warts in a female patient with systemic lupus erythematosus (SLE), who achieved complete remission with a combination approach of surgical debulking and oral isotretinoin at an initial dose of 20 mg/day with a gradual taper of dose over 8 months. She had previously been treated with a combination of topical imiquimod cream and regular fortnightly liquid nitrogen. Although there was partial response, there was no complete clearance. Her condition worsened after topical imiquimod cream was stopped because of her pregnancy. She underwent a combination approach of surgical debulking and oral isotretinoin after her delivery and achieved full clearance for more than 2 years duration. Oral isotretinoin, especially in the treatment of recalcitrant genital warts, is a valuable and feasible option when other more conventional treatment methods have failed or are not possible. It can be used alone or in combination with other local or physical treatment methods.     

Polyphenon E 10% Ointment

Polyphenon E 10% ointment, which contains a mixture of green tea catechins, is indicated for the treatment of external genital and perianal warts (Condylomata acuminata) in immunocompetent patients aged ≥18 years. In two double-blind, multinational studies in adults with external genital and perianal warts, polyphenon E 10% ointment for up to 16 weeks was significantly more effective than vehicle with regard to the complete clearance of all warts (i.e. those at baseline and newly appearing during treatment) [primary endpoint]. In gender subgroup analyses, polyphenon E 10% ointment was more effective than vehicle in both men and women in one of two individual studies, and in pooled data from both studies. Polyphenon E 10% ointment was also significantly more effective than vehicle with regard to several secondary endpoints, including the complete clearance of baseline warts and partial clearance of at least 50% of all warts in both studies. Rates of recurrence of any warts or development of new warts were low (<9%) in both treatment arms during a 12-week follow-up period in both studies. Polyphenon E 10% ointment was generally well tolerated in adults with external genital and perianal warts. According to pooled data from the two clinical studies, the majority of adverse events associated with polyphenon E 10% ointment involved application site and local skin reactions at the treatment site.     

Efficacy of imiquimod 5% cream in the treatment of recalcitrant warts in children

Long-lasting cutaneous warts are a therapeutic challenge, especially widespread or symptomatic recalcitrant warts in children. It can be speculated that natural immunity to these human papillomavirus (HPV)- induced lesions is extremely poor. Therefore ideally treatment should focus on increasing local immune response. Recently imiquimod, a topical immune modifier, has been successfully used in the treatment of external genital warts. Our purpose is to report on our experiences with imiquimod 5% cream applied to therapy-resistant, long-lasting (duration 2-7 years) common warts in children. In 18 children, imiquimod cream was self-applied by the patients or by their parents to the warts twice a day. Assessment for response and occurrence of adverse effects was performed every 4 weeks until clinical cure. Follow-ups could be arranged in 14 of the 18 patients 1-2 years after total clearance. Sixteen of 18 patients experienced total clearance of their warts; 2 showed partial improvement but were lost to follow-up. The mean duration of treatment was 5.8 months. Two of the 14 patients in whom a follow-up was performed showed a small number of new warts after a period of at least 1 year without recurrence. Our data demonstrate that the topical application of imiquimod 5% cream is an effective treatment for long-lasting cutaneous warts in children.     

The role of inosine pranobex in the treatment of herpes zoster and postherpetic neuralgia

The severity of herpes zoster worsens with age and postherpetic neuralgia is almost limited to the elderly (Wildenhoff et al. , 1979, 1981). Acyclovir speeds healing and lessens pain, but has no effect on postherpetic neuralgia (Peterslund et al. , 1981; Bean, Braun & Balfour, 1982). Inosine pranobex (or isoprinosine, inosiplex: trade name Imunovir), an immuno-modulator with low toxicity, is effective in herpes simplex ( Lancet , 1985). Uncontrolled observations indicate a beneficial effect in herpes zoster (Sternberg & Ruiz, 1972).
We report the first double-blind placebo-controlled clinical trial of inosine pranobex in the treatment of herpes zoster and postherpetic neuralgia in the elderly.
Forty-two consecutive patients (19 males, 23 females) over 60-years old and in the first 96 h of symptoms were stratified by sex, duration of pain (up to and/or over 48 h) and localization (trigeminal/other) and were randomly allocated 6 days of placebo or of inosine pranobex tablets. Five clinical and five photographic variables were monitored daily for 7–9 days (Peterslund et al. , 1981). Pain was assessed monthly for a further 3 months. Investigations at entry, 1 and 4 weeks, comprised haematology, biochemistry, viral culture, immunology, including circulating T-cell subsets, and serology, including ELISA and complement fixation tests.
Results, statistically analysed by multiple regression analysis (Peterslund et al. , 1981) and life-table techniques, will be presented.     

咪喹莫特乳膏与二氧化碳激光治疗尖锐湿疣的临床疗效对比

目的：研究尖锐湿疣临床诊断的方法及治疗措施。方法：以我院从2010年6月至2013年6月收治的120例尖锐湿疣患者作为研究对象,将患者随机分为两组,实验组使用咪喹莫特乳膏治疗,对照组采用二氧化碳激光治疗方法。结果：120例患者均采用阴道镜活检确诊为尖锐湿疣,经过系统的治疗以后,实验组的总体有效率为85%,对照组的总体有效率为68.33%,实验组的治疗效果显著优于对照组。结论：尖锐湿疣的临床诊断主要是以阴道镜活检的方法,确诊率能够达到99%以上。目前咪喹莫特乳膏是治疗尖锐湿疣的有效药物,安全性较好,副作用较少,值得在临床中进一步推广。     

Clinical features and outcome of first presentation anogenital warts in men and women

Objective Correlation of clinical features of patients on initial presentation of anogenital warts to outcome of treatment. Setting Outpatient genitourinary medicine clinic. Method Retrospective cohort analysis. Subjects Eighty-three male and 60 female patients attending the clinic with first episode anogenital warts within a 3-month period. Main outcome measures Relapse of warts following treatment. Total time for which treatment was given. Results Following one course of treatment, warts relapsed in 15% of the men, hut in only 37% of the women. After two courses, further relapse occurred in 31% of males and 18% of females (P < 0.001). Treatment for more than 6 months was required for 39% of men, but only 22% of women. Poorer outcome of treatment was related to larger size of warts at presentation. No significant relation was found between outcome and number, site or type of treatment used for warts, or for sexual behaviour or orientation of patients. A previously diagnosed sexually transmitted disease (STD) was reported by 34% of men and 28% of women: 28% of men and 23% of women had an STD diagnosed at the time of presentation with warts. No significant relation was found between outcome and STDs past or concurrent, including HIV. Female patients tended to have smaller warts than men but their better outcome remained significant after controlling for the size of warts. Conclusions Treatment outcome for genital warts is poor and significantly predicted by size of warts at presentation. Female patients have a better outcome from treatment of genital warts than male patients.     

Randomised controlled trial and economic evaluation of podophyllotoxin solution,podophyllotoxin cream,and podophyllin in the treatment of genital warts

OBJECTIVES: To evaluate the efficacy and cost effectiveness of self applied podophyllotoxin 0.5% solution and podophyllotoxin 0.15% cream, compared to clinic applied 25% podophyllin in the treatment of genital warts over 4 weeks. METHODS: We conducted a randomised controlled trial in 358 immunocompetent men and women with genital warts of 3 months' duration or less. RESULTS: In the principal analysis both podophyllotoxin solution (OR 2.93, 95% CI 1.56 to 5.50) and podophyllotoxin cream (OR 1.97, 95% CI 1.04 to 3.70) were associated with significantly increased odds of remission of all warts compared to podophyllin. We performed two further analyses. When subjects defaulting from follow up were assumed to have been cured odds of remission of all warts were also significantly increased both for podophyllotoxin solution (OR 3.04, 95% CI 1.68 to 5.49) and for podophyllotoxin cream (OR 2.46, 95% CI 1.38 to 4.40). When subjects defaulting from follow up were assumed not to have been cured odds of remission of all warts were significantly increased for podophyllotoxin solution (OR 1.92, 95% CI 1.13 to 3.27), but not for podophyllotoxin cream (OR 1.17, 95% CI 0.69 to 2.00). Local side effects were seen in 24% of subjects, and recurrence of warts within 12 weeks of study entry in 43% of all initially cleared subjects, without statistically significant differences between the treatment groups. Direct, indirect, and total costs were similar across the three treatment groups. Podophyllotoxin solution was the most cost effective treatment, followed by podophyllotoxin cream, with podophyllin treatment being the least cost effective. CONCLUSIONS: Self treatment of anogenital warts with podophyllotoxin showed greater efficacy and cost effectiveness than clinic based treatment with podophyllin.     

Polyphenon® E

Treatment of genital warts (condylomata acuminata) is still not completely satisfactory, despite the introduction of imiquimod 5% cream. With the development of Polyphenon E 15% ointment, progress has been made towards optimized, patient-friendly treatment of genital warts. Polyphenon E is a mixture of different polyphenols/catechins from green tea extracts (Camilla sinensis), which are known to have antioxidative, antiinflammatory, anti-proliferative and anticancer activities. In 3 placebo-controlled clinical studies safety and efficacy of Polyphenol E 15% ointment was studied in a total of 1400 patients with genital warts from Europe, North- and South America as well as South Africa. Complete responses with total healing of genital warts were seen in 54.9% of the patients in contrast to 35.4% of patients receiving placebo (p >0.001) (Combined study data). The recurrence rate was 6.2%. Polyphenon E offers special advantages with regard to its very good safety profile. Systemic adverse reactions are unlikely. Mild to moderate local reactions are of short duration. "Drug-holidays" are not necessary and the ointment does not have to be washed off. There is no contraindication for uncircumcised men with genital warts.     

A prospective,open, comparative study of 5% potassium hydroxide solution versus cryotherapy in the treatment of genital warts in men

BACKGROUND

Genital warts are caused by human papillomavirus infection and represent one of the most common sexually transmitted diseases. Many infections are transient but the virus may recur, persist, or become latent. To date, there is no effective antiviral treatment to eliminate HPV infection and most therapies are aimed at the destruction of visible lesions. Potassium hydroxide is a strong alkali that has been shown to be safe and effective for the treatment of genital warts and molluscum contagiosum. Cryotherapy is considered one of the most established treatments for genital warts. No comparative trials have been reported to date on the use of potassium hydroxide for genital warts.

OBJECTIVE

A prospective, open-label, randomized clinical trial was conducted to compare topical potassium hydroxide versus cryotherapy in the treatment of genital warts affecting immunocompetent, sexually active men.

METHODS

Over a period of 10 months, 48 patients were enrolled. They were randomly divided into two groups and selected on an alternative basis for either potassium hydroxide therapy or cryotherapy. While response to therapy did not differ substantially between both treatment modalities, side effects such as local pain and post-treatment hypopigmentation were considerably more prevalent in the groups treated using cryotherapy.

RESULT

In our study, potassium hydroxide therapy proved to be at least as effective as cryotherapy and offered the benefit of a better safety profile.

CONCLUSION

Topical 5% potassium hydroxide presents an effective, safe, and low-cost treatment modality for genital warts in men and should be included in the spectrum of therapies for genital warts.     

国产5％咪喹莫特乳膏治疗生殖器疣荟萃分析

目的：以循证医学的方法对国产5％咪喹莫特乳膏治疗生殖器疣的疗效、安全性以及预防生殖器疣复发的效果进行系统性评价。方法：检索中文科技期刊数据库（CNKI）、中国生物医学文献数据库（CBMDisc），由两名评价者独立提取资料并进行方法学质量评估。试验数据的统计分析采用Co-chrane协作网提供的RevMan4．2．8软件进行。结果：咪喹莫特乳膏单疗组，最终纳入8个临床随机对照试验，Meta分析结果显示，与安慰剂比较，疗效差异有统计学意义；与2．5％氟尿嘧啶软膏比较，疗效差异没有统计学意义。没有严重系统性不良反应的报道。咪喹莫特乳膏联合物理治疗组，最终纳入12个临床随机对照试验，Meta分析结果显示，以观察3个月或6个月没有在原位复发作为痊愈标准，与安慰剂组比较，疗效差异有统计学意义。结论：现有临床证据表明，国产5％咪喹莫特乳膏治疗生殖器疣有确切的疗效和较好的安全性，对预防生殖器疣复发也有确切的疗效。     

A clinical study of efficacy of garlic extract versus cryotherapy in the treatment of male genital wart

Background/Objective

Genital warts are caused by human papilloma virus (HPV) and usually have no promising cure. Garlic (Allium sativum) belongs to Liliaceae family, which has a long history of medicinal use. The garlic extract had antiviral and anticarcinogenic effects and can be effective on complete resolution of cutaneous wart. The aim of this clinical study was to compare the garlic extract effect with cryotherapy in the treatment of male genital wart.

A narrative review of the definition of ‘flare’ in hidradenitis suppurativa

Selecting a topical treatment from among the numerous topical agents for external genital warts remains challenging without clear evidence. Our aim was to evaluate comparatively the efficacy and safety of topical agents for external genital warts using a network meta-analysis. We included all randomized controlled trials that evaluated any topically applied treatment for external genital warts. Using the R package netmeta, network meta-analyses were performed with a frequentist approach. We identified 41 relevant studies comprising 6371 patients. Among conventional agents, podophyllotoxin 0·5% solution (odds ratio 1·94, 95% confidence interval 1·02–3·71) was significantly more efficacious than imiquimod 5% cream for lesion clearance; however, it was associated with a higher overall adverse event rate. Sinecatechins 15% ointment (odds ratio 0·21, 95% confidence interval 0·12–0·34) was significantly less efficacious than imiquimod 5% cream. Idoxuridine, polyhexamethylene biguanide, cidofovir and SB206 showed comparable therapeutic efficacies with conventional therapies. None of the treatments were significantly different from each other with respect to recurrence, patients with severe adverse events, or patients who withdrew because of treatment-related adverse events. Conventional modalities were efficacious and well tolerated, although each of them had their advantages and disadvantages. Additional efficacy and safety studies are warranted for unconventional agents. Linked Comment:   Doiron. Br J Dermatol 2020; 183 :5–6 .