Imiquimod 5% cream for external genital or perianal warts in human immunodeficiency virus-positive patients treated with highly active antiretroviral therapy: an open-label, noncomparative study

Background  Human immunodeficiency virus (HIV)+ patients have an increased risk of anogenital warts. High-risk (HR) human papillomaviruses (HPVs), especially types 16 and 18, are major risk factors for precancerous and cancerous lesions of the anogenital tract, while low-risk (LR) HPVs are associated with benign lesions. Cure of genital warts with ablative techniques, surgical excision, podophyllotoxin or trichloroacetic acid is frequently difficult. Treatment with imiquimod cream showed a total clearance of external genital or perianal warts in about 50% of immunocompetent subjects. However, total clearance was reduced in HIV+ subjects not treated with highly active antiretroviral therapy (HAART).
Objectives  To assess clinically and by monitoring HPV content the efficacy of 5% topical imiquimod to treat anogenital warts in HIV+ subjects with at least partially restored immune functions.
Methods  Fifty HIV+ patients successfully treated with HAART (total CD4+ cells ≥ 200 cells mm⁻³ and plasma HIV RNA load < 10⁴ copies mL⁻¹) with anogenital warts were included. Imiquimod 5% cream was applied on external genital or perianal warts three times weekly for up to 16 weeks. Warts were tested at entry and after treatment for human LR- and HR-HPV DNA.
Results  Total wart clearance was observed in 16 of 50 (32%) patients at week 16. At enrolment, HPV DNA was present in more than 90% of lesions with a majority of lesions co-infected by HR- and LR-HPV. At study end, the HPV load decreased or became undetectable in 40% of cases studied.
Conclusions  Imiquimod 5% cream did not show safety concerns and is suitable for use in HIV+ subjects with anogenital warts and successful HAART treatment.     

Imiquimod 5% cream is an acceptable treatment option for external anogenital warts in uncircumcised males

OBJECTIVES: To determine the safety and efficacy of imiquimod (Aldara) 5% cream in the treatment of prepuce-associated warts in uncircumcised males. METHODS: An open-label study in six UK medical centres with 35 uncircumcised males with prepuce-associated warts treated with imiquimod 5% cream three times per week for up to 16 weeks. Other anogenital warts were also treated. RESULTS: Three times weekly application of imiquimod was found to be safe, with erythema as the most commonly reported local skin reaction. Forty per cent of patients had complete clearance of anogenital warts within 16 weeks. CONCLUSIONS: Imiquimod cream at a dosing regimen of three times per week, is effective and has an acceptable safety profile in the treatment of prepuce associated warts and other external anogenital warts in uncircumcised males.     

Topical imiquimod 5% cream in external anogenital warts: a randomized, double-blind, placebo-controlled study

The complete treatment of anogenital warts has not been obtained with any combination of methods; therefore, new methods are still under investigation. In this study the activity and side effects of imiquimod 5% cream were investigated. The study group consisted of 23 male and 11 female volunteers and the control group of 9 male and 2 female volunteers. Patients applied the cream three times a week, every other day in the evenings for a period of 12 weeks. After the treatment, patients were regularly monitored for six months for recurrences. At the end of the study, 23 (69.7%) patients (all of females and 54.5% of males) in the study group displayed a complete clearance, 9 patients displayed 50-90% clearance and 1 patient displayed less than 50% clearance. In the control group, only 1 patient displayed a complete clearance, 1 patient displayed 50-90% clearance, and the other 8 patients showed no alteration in the lesions. These results were statistically significantly different (p<0.01). In 15 patients in the study group, no side effects were reported; the most frequently seen side effects were erythema and erosion. In six patients that were observed for a period of six months, recurrences occurred. Imiquimod 5% cream is a topically applied medicament that should be considered as an effective and reliable medical option in the treatment of anogenital warts.     

Vagarious successful treatment of recalcitrant warts in combination with CO2 laser and imiquimod 5% cream

Abstract

Background. Imiquimod 5% cream is widely regarded as a safe and effective option when treating recalcitrant warts, owing to the ointment's negligible side effects. However, our observations highlighted case of a patient incurring severe adverse reactions due to application of the cream, although the treatment proved successful in curing recalcitrant warts which had developed on the external auditory canal and external ear. Methods. All lesions were entirely removed with short-pulsed CO₂ laser. As soon as the wound-healing process was completed, imiquimod 5% cream was self-applied on the healing wounds once daily for 5 days per week in a total of 2 weeks. Results. The patient appeared normal after the CO₂ laser treatment and experienced severe redness, itching, exudation, and incrustation after a 2-week imiquimod 5% cream therapy. All lesions showed no recurrence during the 12-month followed-up process. Conclusions. We concluded that a feasible treatment modality to cure recalcitrant cutaneous warts is in combination of CO₂ laser and imiquimod. Immunoenhancement plays an important role in the treatment of recalcitrant warts.     

High viral load of human wart-associated papillomaviruses (PV) but not β-PV in cutaneous warts independent of immunosuppression

Background  A broad spectrum of human papillomaviruses (HPV) has been detected in warts from immunocompetent patients and a much more diverse range from immunosuppressed organ transplant recipients (OTR).
Objectives  To determine the HPV types in warts from OTR, we assessed present infections of mucosal (α-PV), wart-associated (α-, μ- and ν-PV) and cutaneous HPV types (β-/γ-PV) in immunocompetent patients and OTR.
Patients/methods  Forty-one warts from 29 immunocompetent patients (non-OTR) and 53 warts from 33 OTR were analysed for DNA of human α-, β-, γ-, μ- and ν-PV. For frequent types viral load was determined by quantitative real-time PCR.
Results  Compared with non-OTR prevalence of cutaneous HPV (79% vs. 49%, P  <   0·01) and the number of multiple infections (62% vs. 17%, P  <   0·0001) were significantly increased. The mean viral load of the wart-associated HPV was more than 10⁵-fold higher compared with human β-PV in both cohorts.
Conclusions  The high load of wart-associated HPV suggests an active role of these viruses rather than cutaneous types in warts independent of immunosuppression; however, the substantial fraction of warts with low HPV genome copies remains to be explained.     

Bowenoid papulosis successfully treated with imiquimod 5% cream

A 24‐year‐old healthy Japanese female was diagnosed as having bowenoid papulosis in the genital area. The histopathological findings revealed acanthosis, papillomatosis, dyskeratotic cells and clumping cells with mild atypical nuclei. Human papillomavirus type 16 was detected in the lesion. The lesion was successfully treated with topical imiquimod 5% cream after 2 months. Imiquimod 5% cream is a potentially effective treatment modality for lesions that are difficult to treat with surgical excision.     

Self-administered topical 5% imiquimod for the treatment of common warts and molluscum contagiosum

BACKGROUND: Despite numerous therapeutic options the treatment of common warts and molluscum contagiosum remains unsatisfactory for both patients and physicians. Imiquimod, a novel topical immune response modifier, has been successfully used for the treatment of external anogenital warts. OBJECTIVES: We aimed to evaluate the safety, tolerance and efficacy of imiquimod for the treatment of common cutaneous warts and mollusca that were resistant to previous therapeutic interventions. METHODS: Imiquimod 5% cream was self-applied by the patients to the warts or mollusca once daily for 5 days per week and left in place overnight. Assessment for response and the occurrence of side-effects was performed every 4 weeks until clinical cure or up to a maximum of 16 weeks. RESULTS: Twenty-eight of 50 (56%) patients with warts achieved a total clearance (n = 15; 30%) or a > 50% reduction in wart size (n = 13; 26%) after a mean treatment period of 9.2 weeks. Twelve of 15 (80%) patients with mollusca achieved a total clearance (n = 8; 53%) or a > 50% reduction in molluscum size (n = 4; 27%). There was no difference in response with regard to gender, human immunodeficiency virus serostatus or atopic predisposition. CONCLUSIONS: Patient-applied 5% imiquimod cream holds promise as an effective treatment of common warts and mollusca in a difficult-to-treat patient population.     

Imiquimod: potential risk of an immunostimulant

A 19-year-old woman with severe HLA B27 spondyloarthropathy whose disease was controlled on cyclosporin, methotrexate and prednisolone had human papillomavirus infection and developed cervical dysplasia and a large number of cutaneous and vulval warts. These were not responsive to cryotherapy, salicylic acid or cimetidine, so she was treated with topical imiquimod 5% cream. Two weeks after starting this treatment she had a significant flare of her spondyloarthropathy. She was so ill that she stopped using the imiquimod cream. She had full resolution of her warts after 3 weeks' treatment with imiquimod cream, but her spondyloarthropathy took more than 3 months to improve, despite significant augmentation of her immunosuppression. This case highlights the potential risk of using imiquimod cream (an immunostimulant) in a patient who has a condition requiring immunosuppression, such as autoimmune disease or an organ transplant.     

A case of severe eczema following use of imiquimod 5% cream

Imiquimod 5% cream, an immune response modifier licensed for treatment of external ano-genital warts and superficial basal cell carcinomata, is known to cause local erythema, oedema and, rarely, exacerbation of psoriasis. We describe a case of exacerbation of eczema following application of this cream in a man with penile warts.     

Detection and typing of human papillomavirus in cutaneous warts of patients infected with human immunodeficiency virus type 1

BACKGROUND: Cutaneous warts are caused by human papillomavirus (HPV). To date, more than 120 different types of HPV are known, of which 80 have been completely characterized. Prevalence studies on types of HPV present in cutaneous warts have been carried out in immunocompetent individuals and immunosuppressed organ allograft recipients, but not in human immunodeficiency virus (HIV)-positive patients. OBJECTIVES: To determine the HPV types present in cutaneous warts of HIV-infected patients. METHODS: Twenty-five biopsies of cutaneous warts from HIV-infected patients and 14 samples from control non-HIV-infected patients were studied. HPV detection was performed by polymerase chain reaction using two sets of primers: MY09/MY11 and RK91. The type of HPV was determined by restriction fragment length polymorphism analysis and direct sequencing of the amplified products. RESULTS: HPV DNA was detected in 64% of cutaneous warts from HIV-infected patients and in 79% of samples from the control group. The HPV types identified in HIV-infected patients were: HPV 2 (38%), 57 (31%), 27 (12%), 6 (12%) and 7 (6%). HPV 2/27/57 predominated in both groups, being present in 81% of lesions from HIV-infected patients and 82% of samples from non-HIV-infected patients. HPV 6, a genital HPV type rarely found in cutaneous lesions, was detected in two warts from HIV-infected patients and in one lesion of the immunocompetent group. HPV 7, characteristically associated with butcher's warts, and recently detected in oral and perioral lesions of HIV-infected patients, was found for the first time in a non-facial lesion of an HIV-infected patient. CONCLUSIONS: This is the first study evaluating the prevalence of HPV types in cutaneous warts of HIV-infected patients and immunocompetent individuals in Brazil.     

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。     

Imiquimod 5% cream for the treatment of nasal lesion of metastatic renal cell carcinoma

Many reports have shown the efficacy of topical imiquimod in patients with skin carcinoma. This effect is based on the activity of imiquimod as an immune-response modifier. The present authors hypothesized that this agent could also be used to treat skin metastatic lesion from renal cell carcinoma. The present authors report the case of a 54-year-old man who presented with a metastasis renal cell carcinoma lesion on his nose. He had a history of right nephrectomy performed 4 years previously. The present authors started him on topical treatment with imiquimod 5% cream three times a week for his nose lesion. A reduction of the lesion was observed after 2 months, and during the following 12 months no sign of recurrence was observed.     

Imiquimod 5% cream as a therapeutic option for extramammary Paget's disease

A wide local excision is the standard treatment for extramammary Paget's disease (EMPD), though this treatment often leads to permanent anogenital mutilation and functional impairment. The purpose of our study is to evaluate the efficacy and safety of the topical application of imiquimod 5% cream for non‐invasive EMPD. We examined nine patients with EMPD. Eight of the nine patients were treated with imiquimod 5% cream three times per week for 16 weeks; one case was treated for 6 weeks. The response rate was 100% including five complete remissions. Local irritation was observed in three patients, which was controlled by a provisional withdrawal of the treatment. These results suggest that imiquimod 5% cream may be considered an alternative therapeutic option for the treatment of non‐invasive EMPD.     

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.     

Topical treatment for plantar warts: A systematic review

There are a wide variety of treatments for plantar warts, but none has been shown to be effective in all patients. We aimed to perform a systematic review of the efficacy of different topical treatments on plantar warts. Systematic electronic searches (Pubmed, Cochrane Library, Embase, and Web of Science) were conducted in April 2020. Meta‐analyses, systematic reviews, and retrospective or prospective clinical trials of the effects of topical and nonsurgical treatments of plantar warts were included. Two authors performed the study selection and data extraction. Any discrepancies between the two reviewers were discussed with a third reviewer. Forty‐four studies were included. The average cure rates of the most frequent treatments were variable across the studies: cryotherapy (45.61%), salicylic acid (13.6%), cantharidin‐podophyllin‐salicylic acid formulation (97.82%), laser (79.36%), topical antivirals (72.45%), intralesional bleomycin (83.37%), and intralesional immunotherapy (68.14%). Twenty‐two studies (50%) had a level of evidence 1b and grade of recommendation A, five studies (11.4%) had a level of evidence 2b and grade of recommendation B, two studies (4.5%) had a level of evidence 3b and grade of recommendation B, and 15 studies (34,1%) with a level of evidence 4 and grade of recommendation C. First‐choice treatments for common warts, such as cryotherapy and salicylic acid, have low‐cure rates for plantar warts. Other treatments, such as CPA formulation, immunotherapy, and intralesional bleomycin, which have compassionate use, have higher cure rates. This review should stimulate future high‐quality research to evaluate these specialized treatments.     

The descriptive epidemiology of warts in the community

Warts are common skin infections caused by human papillomavirus (HPV) and affect most people sometime in their life. A number of epidemiological studies on the prevalence of warts have been completed in schools, various occupational groups, general practices and hospitals. All studies have relied on a subjective measure for the diagnosis of warts. Cross-sectional studies completed in schools have shown the prevalence in children to vary from 2 to 20%. Occupational handlers of meat, poultry and fish have a higher prevalence than other workers. Children and young adults are the groups most affected. Future studies are needed to investigate the true frequency of warts in the community and the likelihood of an individual developing these lesions during his/her lifetime.     

5％咪喹莫特乳膏治疗外生殖器/肛周疣随机对照研究

目的评价5％咪喹莫特乳膏（艾达乐）治疗外生殖器／肛周疣的有效性和安全性。方法采用随机、双盲、平行对照、七个中心临床研究。患者随机入组，一组患者先接受咪喹莫特治疗16周或至所有基线疣消失，然后给予赋形剂4周。另一组患者先接受赋形剂治疗4周，然后再接受咪喹莫特治疗16周或至所有基线疣消失。每周外用乳膏3次（晚上应用，至少保留8h），每4周评估一次临床疗效。结果共144例患者人选。在研究结束时（20周），综合两个治疗组合并显示，基线疣计数减少≥50％的患者为75．0％（意向性治疗分析，ITT）和83．5％（符合方案完成试验集分析，PP），疣完全清除率分别为79．9％（ITT分析）和89．8％（PP分析）。在第4周时，咪喹莫特组基线疣计数减少≥50％的患者为48．6％，赋形剂组为19．4％，P=0．0004；咪喹莫特组疣完全清除率为22．2％，赋形剂组为6．9％，P=0．009。最常见的不良事件发生是用药部位的皮肤反应（38．9％），无严重不良事件发生。结论咪喹莫特乳膏治疗外生殖器／肛周疣疗效明显优于赋形剂，每周3次，疗程16周，安全有效，使用方便。