Ingenol Mebutate Gel 0.05% in the Treatment of Anogenital Warts: A Prospective Controlled Trial Comparing It With Topical Podophyllin Solution 25.

BACKGROUND: Anogenital warts (AGWs) are a common therapeutic challenge. All therapies are associated with burning, pain, and frustrating high rate of recurrence. The search for a new alternative continues. Recently, a diterpene ester extracted from the Euphorbia peplus plant (ingenol mebutate [IM]) has been shown to possess activity against AGWs. OBJECTIVE: This study aimed to compare and evaluate the therapeutic efficacy and safety of topical 0.05% ingenol gel with another herbal extract medication (topical 25% podophyllin solution) in treatment of AGWs. METHODS: This was a comparative single blinded nonrandomized, 2-arm trial of ingenol 0.05% gel versus podophyllin solution 25% administered up to 6 times to patients with AGWs. To evaluate the therapeutic efficacy, the complete clearance rate and recurrence rate were assessed 1 and 12 weeks after last treatment, respectively. Safety was assessed by occurrence and severity of pain and local skin reaction (LSR). RESULTS: Of 31 and 36 patients in the IM group and podophyllin group who completed the study, initial complete resolution was observed in 20 (64.5%) and 14 (38.9%) patients, respectively (P = 0.03). The initial clearance was faster in the IM group (2.00 ± 0.91 weeks) compared with the podophyllin group (4.21 ± 1.05 weeks, P = 0.00). After 3 months, recurrence was seen in 13 (65.0%) of 20 patients in the IM group and 6 (42.8%) of 14 in the podophyllin group (P = 0.20). The number of patients with complete resolution after 3 months was not different between the 2 groups (7/31 in the IM group and 8/36 in the podophyllin group, P = 0.97). The mean ± SD severity scores for LSR and pain in the IM group were 6.65 ± 1.76 and 6.13 ± 2.57, respectively, which was significantly higher than their scores (3.39 ± 1.57 and 2.58 ± 1.38) in the podophyllin group (P = 0.00). CONCLUSION: Ingenol mebutate 0.05% gel is effective as podophyllin 25% solution in treating AGWs, with further benefit of being much more rapid. However, high recurrence rate, sever pain, and LSR limit its use.

Real-life treatment of cutaneous warts with cantharidin podophyllin salicylic acid solution.

Patients often request treatment of their burdensome cutaneous warts. However, a safe and effective treatment for cutaneous warts is lacking. This study evaluates treatment outcome, side effects, and patient satisfaction after topical application of cantharidin 1% podophyllin 2% salicylic acid 30% (CPS1) solution in a large series of children and adults with cutaneous warts. Fifty-two children and 83 adults with warts, treated with CPS1 solution between October 2012 and October 2014, were included. Complete clearance of warts occurred in 86.5% of children and 62.7% of adults treated with CPS1 solution (p < .01). Resolution of warts was partial in 3.9 and 24.1% and absent in 9.6 and 13.2% of children and adults respectively. Side effects were present in 41.2% of children and 46.3% of adults (p = .7). Most common side effects were blistering, pain, and burning sensation. No serious adverse events occurred. On a 10-point scale, median patient satisfaction score was 9.0 (interquartile range 7.8-10.0) and 8.0 (interquartile range 5.1-9.7) for children and adults respectively (p < .01). CPS1 solution is a safe and promising treatment modality with a high clearance and high patient satisfaction rate for the management of cutaneous warts, particularly in children.

ß-Apopicropodophyllin functions as a radiosensitizer targeting ER stress in non-small cell lung cancer.

AIMS: In this study, we examined whether ß-apopicropodophyllin (APP) could act as a radiosensitizer in non-small cell lung cancer (NSCLC) cells. MAIN METHODS: The in vitro radiosensitizing activity of APP was demonstrated with clonogenic assay, immunoblotting, Annexin V-Propidium iodide (PI) assay, BrdU incorporation, detection of mitochondrial ROS/intracellular of H2O2, mitochondrial membrane potential detection, and performing of isolation of mitochondrial and cytosolic fractions. The in vivo radiosensitizing activity of APP was determined in xenografted mice with co-treatment of APP and IR based on measurement of tumor volumes and apoptotic cell death. KEY FINDINGS: The results of a clonogenic assay indicated that a combination of APP and γ-ionizing radiation (IR) inhibits cell growth and increases cell death in NSCLC cells. Several signal transduction pathways were examined for their potential involvement in the apparent radiosensitization effect of APP, as assessed by immunoblotting analyses and mitochondrial potential determination in vitro. Treatment of NCI-H460 cells with 15 nM APP and NCI-H1299 cells with 10 nM APP yielded dose-enhancement ratios of 1.44 and 1.24, respectively. Enhanced ER stress, disrupted mitochondrial membrane potential, and increased reactive oxygen species (ROS) were observed in cells co-treated with APP and IR, and this was followed by the cytosolic release of cytochrome c and consequent activation of caspase-3 and -9. Notably, inhibition of JNK, which prevents caspase activation, blocked the APP/IR-induced activations of ER stress and apoptotic cell death. In NCI-H460 or NCI-H1299 cell-xenografted mice, APP/IR treatment delayed the time it took tumors to reach a threshold size by 22.38 and 16.83 days, respectively, compared with controls, to yield enhancement factors of 1.53 and 1.38, respectively. SIGNIFICANCE: APP has a radiosensitizing function derived from its ability to induce apoptotic cell death via activation of ER stress, disruption of mitochondrial membrane potential, and induction of the caspase pathway.

Combined treatment of anogenital HPV infection with cryodestruction, podophyllin 25% and post-ablation immunomodulation with sinecatechins 15% ointment - a retrospective analysis.

External genital warts, caused by human papillomavirus, have a significant clinical, epidemiological, and financial impact, including the risk for malignant transformation. Treatment modalities include: (a) destructive (ablative); (b) cytotoxic (proapoptotic) and (c) immunomodulatory, with success and recurrence rates varying from 23% to 94% and from 4.1% to 77%, respectively. Most studies evaluated only single modality therapy, with few reports examining a combined approach for external genital warts management. The introduction of sinecatechins ointment in recent years has resulted in very low recurrence rates of 4.1-10.6%, despite lower initial clearance rates than ablative methods. We present a retrospective review of 27 patients who underwent combined therapy for external genital warts by using one or two sessions of cryodestruction combined with 25% podophyllin as the cytotoxic agent, and post-ablation immunomodulation with topical sinecatechins 15% ointment. This approach resulted in an excellent initial clearance rate of 96.3% with a recurrence rate of 7.4% after a total period of six months of follow-up. We suggest the importance of the combined approach in external genital warts management including post-ablative immunomodulation to augment the immune response and combat the residual latent infection. We hope to encourage trials examining the combined approach to the treatment of external genital warts.

Giant anal condyloma (giant condyloma acuminatum of anus) after allogeneic bone marrow transplantation associated with human papillomavirus: a case report.

INTRODUCTION: Condyloma acuminatum are caused by human papillomavirus. Giant condyloma acuminatum is a locally invasive, destructive, and large sized mass. Risk factors for the development of giant condyloma acuminatum include an immunodeficient state, such as human immunodeficiency virus infection, post-organ transplantation, or post-allogeneic bone marrow transplantation. However, reports of giant condyloma after bone marrow transplantation are extremely rare (0.3 to 1.3%). The standard treatment for giant condyloma acuminatum is recommended as wide surgical resection due to its high rate of success and low rate of recurrence. CASE PRESENTATION: A 31-year-old Korean man presented to our hospital with anal discomfort for more than one month due to a protruding mass. He had a history of BCR-ABL-positive acute lymphoblastic leukemia and had undergone an allogenic stem cell transplantation. Gross findings revealed a large perianal cauliflower-like mass over 7cm in size with invasion of the anal orifice. He was diagnosed with giant anal condyloma occurring after an allogeneic bone marrow transplantation. However, we achieved successful treatment using a combination of topical podophyllin and cryotherapy and transanal surgical excision, followed by bleomycin irrigation. CONCLUSIONS: We report an extremely rare case of giant condyloma acuminatum of anus due to human papillomavirus type six in a patient with acute lymphoblastic leukemia following an allogeneic bone marrow transplantation. The tumor was successfully treated with a combination of topical podophyllin and cryotherapy and transanal surgical excision, followed by bleomycin irrigation.

Efficacy of combination therapy of oral zinc sulfate with imiquimod, podophyllin or cryotherapy in the treatment of vulvar warts.

AIM: Zinc sulfate is beneficial in the treatment of epithelial warts. We conducted this study to compare the efficacy of combination therapy of oral zinc sulfate with conventional treatments in the treatment of vulvar warts. MATERIAL AND METHODS: This study was a randomized controlled trial. The sample size was 42 in each group. Women aged 20-50 years were placed by the block randomized method into six groups: the podophyllin-, imiquimod- and cryotherapy-treated groups, and another three groups receiving 8-week combination therapy of 400 mg oral zinc sulfate with one of the above-mentioned treatments. Data were analyzed using anova and Fischer's exact test with spss16. RESULTS: A total of 228 patients were recruited and completed the study in six treatment groups. No significant difference was observed in the response to treatment among these groups. Relapse after 6 months was significantly higher in the podophyllin-, imiquimod- and cryotherapy-treated patients compared to patients receiving these treatments in combination with oral zinc sulfate (P<0.05). CONCLUSIONS: Combined therapy of oral zinc sulfate with conventional treatments of vulvar warts appears to reduce the relapse rate.

Giant disseminated condylomatosis in SLE.

INTRODUCTION: Females with systemic lupus erythematosus (SLE) have higher prevalence of human papillomavirus (HPV) infection, which can lead to the development of warts. Herein we report the first case of giant disseminated condylomatosis (GDC) in a SLE female on mycophenolate mofetil (MMF). CASE REPORT: The patient, a 33-year-old, Black female, was diagnosed with SLE during her first pregnancy in 2003 based on the features of arthritis, skin rash, seizures, nephritis and presence of antinuclear antibodies. Her pregnancy resulted in preterm delivery of a stillborn fetus at 28 weeks. Since that time she has been treated with steroids and different regimens of immunosuppressive drugs such as cyclophosphamide, azathioprine and lately MMF. In the last few years she presented GDC involving the genital area in addition to skin on the lower abdomen. Topical therapy with trichloroacetic acid, imiquimod and podophyllin was only partially effective. Different types of HPV were identified in the lesions, being HPV-11 in abdomen, HPV 6, 11, 42 in vulva, HPV-6, 11 in vagina and HPV-6, 11 in endocervix. CONCLUSIONS: GDC may be a complication of SLE, secondary to the disease itself, its treatment or other factors not yet identified.

A new topical treatment protocol for oral hairy leukoplakia.

OBJECTIVE: The aim of this study was to present a new topical treatment protocol for oral hairy leukoplakia (OHL), consisting of a 25% podophyllin resin with a 1% penciclovir cream (PP), and to compare this topical treatment protocol's efficacy with that of 2 other topical treatment protocols: a 25% podophyllin resin (P) and a 25% podophyllin resin with a 5% acyclovir cream (PA). STUDY DESIGN: Forty-two human immunodeficiency virus-positive patients with 69 OHL lesions were randomly treated using P, PA, or PP (14 patients in each topical treatment protocol). Clinical healing was determined when the white plaque could no longer be seen in the primary location of the lesion. Topical treatment performance was evaluated by clinical healing within each week of topical treatment protocol as well as by the recurrence of the lesion. Statistical survival analysis was performed using a Cox proportional hazards model. RESULTS: Approximately 55% of the patients presented with clinical healing of OHL within 7-8 weeks of each topical treatment protocol. After the sixth week, the PA treatment protocol presented a faster clinical healing rate of OHL. Recurrence was observed in 3 and 7 OHL lesions treated with P and PP treatment protocols, respectively. CONCLUSIONS: The PP treatment protocol proved to be effective; however, the PA treatment protocol was more effective in the clinical healing rate for OHL than P and PP after the sixth week of treatment, and no recurrent OHL was observed in the PA treatment group.

Current therapy for condyloma acuminata of the patients attending female STD Unit, Siriraj Hospital.

OBJECTIVE: To describe the treatment pattern of condyloma acuminata in female. MATERIAL AND METHOD: The 5-year medical records of 449 women treated for genital condyloma acuminata at the Gynecologic Infectious Diseases and Female Sexually Transmitted Disease (GID-FSTD) unit were reviewed. Data included the distribution of age, client by category, anatomical site and size, serologically coexisting sexually transmitted infection (STI), and treatment modalities. RESULTS: About half, 50.1%, of treatment was the application of topical trichloroacetic acid; followed by podophylline in the proportion of 35.5%. While the electric cauterization and imiquimod applications were uncommon therapy. Two-fifth ofthe subjects, 40.7%, was completely cured, and the remaining cases required additional management. CONCLUSION: The present setting, the wide range of treatment available is reflection of the fact that there is no ideal management.

Podophyllin, but not the constituents quercetin or kaempferol, induced genotoxicity in vitro and in vivo through ROS production.

The genotoxic potential of podophyllin (PD) was investigated in this study. PD increased bacterial revertants and abnormal chromosomal structures in a concentration-dependent manner, both with and without metabolic activating enzymes, and increased the incidence of micronuclei in imprinted control region mouse reticulocytes. Results from three studied constituents of PD, such as podophyllotoxin, kampferol, and quercetin, suggested that the mutagenic effect of PD was not due to the presence of podophyllotoxin, kampferol, and quercetin and might be related to other components and the formation of reactive oxygen species. The detailed mutagenic mechanisms need further investigation, and the medicinal use of PD needs to be cautioned against.

Podophyllin reaction mimicking Bowen's disease in a patient with delusions of verrucosis.

A 40-year-old woman presented with a delusion of warts on the forehead, for which she was applying podophyllin toxin. A skin biopsy was taken, which showed prominent mitotic figures in the basal and suprabasal layers of the epidermis and apoptotic keratinocytes. Histopathologically Bowen's disease was suspected, but was discounted after clinicopathological correlation was obtained and showed absence of epidermal atypia or disorganization. This case demonstrates the histological resemblance of podophyllin reaction to Bowen's disease. Differentiation of self-inflicted from organic skin disease may be difficult, especially where histopathological findings are confounded by cutaneous application of toxins.

[Clinical and benign aspects of human papillomavirus-associated lesions]. / Aspects cliniques bénins de l'infection à papillomavirus humains.

Human papillomaviruses (HPV) are found in most human epithelia and some tumors. Most HPV strains associated with cutaneous lesions belong to three types, named alpha, beta and gamma. Although the causal link between genital human papillomavirus infection and cervical neoplasia is well established, the role of beta-HPV in non melanoma skin cancers is unclear. HPV mainly causes benign cutaneous lesions on the hands and soles. Genital HPV infection is the most common sexually transmitted infection. It is generally asymptomatic. The genitals can be infected by two low-risk HPV types (6 and 11), which are responsible for benign anogenital warts (condylomata acuminata). The implications of anogenital warts in children are highly controversial as regards sexual abuse. Treatments (chemical, physical or immunological) are lengthy, expensive, inconvenient and often painful. Recurrence is frequent because of HPV persistence in perilesional skin.

A random clinical trial study to assess the efficiency of topical applications of podophyllin resin (25%) versus podophyllin resin (25%) together with acyclovir cream (5%) in the treatment of oral hairy leukoplakia.

OBJECTIVE: The objective of this study was to assess the efficiency of topical applications of podophyllin resin (25%) (P) versus podophyllin resin (25%) together with acyclovir cream (5%) (PA) in the treatment of oral hairy leukoplakia (OHL) in accordance with the following criteria: (1) number of applications necessary for the total clinical resolution of OHL; (2) correlation between the decrease of lesion size and the number of applications; (3) total clinical resolution of OHL; and (4) clinical reevaluation 12 months after the end of treatment. STUDY DESIGN: Forty-six OHLs were treated with P (P group) or with PA (PA group). Applications were performed weekly. Student t, Fisher exact, and Pearson correlation tests were used for statistical analysis. RESULTS: All 24 lesions from the PA group presented total clinical resolution while 4 lesions from the P group did not. The P group required up to 25 applications performed weekly while the PA group required up to 18. Observed was a negative significant association between the size of the lesions and the number of applications performed weekly in the PA group. CONCLUSIONS: The present study demonstrated the following: (1) P and PA topical treatments presented a similar average number of applications performed weekly; (2) both groups showed the same clinical response at 12 months post-therapy; and (3) PA presented a 100% clinical resolution and a continuous decrease in OHL size over the course of weekly applications.

How and when to treat molluscum contagiosum and warts in children.

Warts and molluscum contagiosum are common skin diseases in children and are usually self-limiting. The decision of whether to treat children with molluscum or warts should be individualized to the patient and his or her family. Considerations include how symptomatic the lesions are, the extent and duration of disease, the ability of the child and the parents to tolerate and comply with treatment recommendations, and any underlying medical conditions (Table, see page 219). Recurrences of molluscum contagiosum and especially warts are common, and realistic expectations regarding the potential for treatment failure and recurrence should be discussed with the child and his or her family prior to initiating any therapy. As pediatric practitioners, we all remain acutely aware of our patients' physical and psychological development and the potential for any intervention to influence this development. Although various treatment modalities now exist for the treatment of these viral diseases, any intervention should be balanced against these considerations.

Patterns of treatment and resource utilization in the treatment of external genital warts in England and Wales.

Our objective was to identify patterns of treatment and resources used in achieving complete clearance of external genital warts (EGWs) A retrospective case note review was carried out at six genitourinary medicine (GUM) clinics in the UK. Case notes from 2366 patients presenting with EGWs were reviewed and 1200 patients with complete episodes of care were identified. Analysis showed that staff-applied therapy dominated treatment practice but there was considerable diversity in treatment modalities across study sites. The average number of visits was 5.71 visits for males: 6.25 visits for females but a substantial minority of patients attended significantly in excess of these averages. Approximately two-thirds of patients failed to achieve complete clearance of warts with their initial therapy. There is little consistency in treatment patterns of care for EGWs across the sites studied. Initial therapy choices are largely ineffective, requiring changes in treatment modality and multiple clinic visits. Increased utilization of patient-applied therapies might result in increased cost effectiveness.

Successful treatment of bowenoid papulosis in a 9-year-old girl with vertically acquired human immunodeficiency virus.

A 9-year-old black girl with vertically acquired human immunodeficiency virus (HIV) and no history of condyloma acuminata presented with a 4-year history of enlarging and spreading dark brown flat papules in the perineum. Some of the lesions were confluent and extended from the clitoris to the labia majora and posteriorly to the buttocks and perianal region. A biopsy of one of the lesions showed bowenoid features. Our patient had a normal Pap smear, but vaginal and cervical biopsy specimens revealed human papillomavirus type 16. Therapy with topical imiquimod cream every other day was started, but little improvement was noted after 2 months. Application of 25% podophyllin every 4 to 8 weeks was added, and improvement was noted within 1 month. After 1 year of treatment, the patient had complete resolution of all lesions, and she has had no further appearance of lesions. Our case emphasizes the need for increased awareness of the potential for development of bowenoid papulosis in HIV-positive children as well as the successful treatment of our patient with topical therapy alone.