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PubMed2004

Local expression of tumor necrosis factor-alpha and interleukin-4 mRNA in different types of warts.

The natural history of warts shows considerable variations between individuals, ranging from spontaneous regression to prolonged persistence. The level of cytokines participate in the immune response to human papilloma virus. This work investigates local expression of T-helper1 (Th1)/ T-helper2 (Th2)/ cytokines in a trial to disclose the different immunological mechanisms affecting the natural history of warts. A total of thirty patients suffering from different types (common, plane, plantar and anogenital) of viral warts were included. An excision biopsy was used to assess tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) expression. Local expression of TNF-alpha (Th1) and IL-4 (Th2) in wart tissue was determined using in-situ hybridization technique. The cytokines probes used in this assay detect messenger RNA (mRNA) in wart tissue. Local expression of TNF-alpha mRNA was higher in viral wart patients compared to healthy control (P < 0.01), while local expression of IL-4 was not significantly higher in patients compared to control (P > 0.05). Statistical analysis was done to determine whether variations in cytokine mRNA expression depend on wart location or clinical types. In conclusion, immunoreactivity to warts is likely to be associated with a predominant Th-1 or mixed Th-1/ Th-2 cytokine mRNA expression profile. However, it does not appear to be a simple causal relationship between expression of a Th-1 pattern and clearance.

Adolescent↗
PubMed2006

Treatment of disseminated facial warts through contact immunotherapy with diphenylcyclopropenone (DPCP).

This paper highlights the effect of diphenylcyclopropenone (DPCP) sensitization on warts resistant to other treatments and is interesting in views of the fact that all the facial warts apparently responded. To analyze the efficacy and side-effects of DPCP treatment of viral warts, a prospective study was designed to follow six patients with chronic and resistant facial warts through immunotherapy sensitization with diphenylcyclopropenone for 10 weekly sessions. Patients were first sensitized with 2 percent DPCP and then followed by weekly maintenance of 0.001-1 percent DPCP in acetone on facial warts until mild contact dermatitis was obtained. After application of DPCP to the warts of the face, all of the facial warts became inflamed and resolved. DPCP appears to be a valuable, safe, and well-tolerated treatment for resistant and chronic facial warts.

Administration, Cutaneous↗
PubMed1991

Intralesional injection of bleomycin sulphate into resistant warts in renal transplant recipients versus non-transplant warty patients.

Sixteen adult renal transplant patients and 20 non-transplant patients with warts underwent intralesional therapy with bleomycin sulphate. One unit/ml bleomycin sulphate was injected in 93 warts in renal transplant recipients and 100 warts in non-transplant patients with proven resistance to conventional treatment for at least 6 months. The treatment was compared with a normal saline placebo injected into the paired warts in the same patient. Thirty-four out of 93 warts (37%) in renal transplant recipients vs. 59 out of 100 warts (59%) in non-transplant patients were completely cured after one to three injections. We found bleomycin completely ineffective in 56 warts (60%) in renal transplant recipients, but ineffective in only 17 warts (17%) in non-transplant warty patients. None of the patients treated experienced any side effects except for local pain which was well tolerated, especially by non-transplant patients.

Adolescent↗
PubMed1991

Nongenital warts: classification and treatment options.

Common, plantar and flat warts are the primary classes of nongenital warts. Although spontaneous remission does occur, all warts should be treated to avoid spreading. Common warts often develop in the periungual region of the fingers. This type of wart generally can be removed with cryotherapy, topical application of salicylic acid or occlusive taping. Plantar warts are found over pressure points of the heel or metatarsal heads. They are also treated with cryotherapy or salicylic acid. Flat warts are commonly seen on the dorsum of the hands or on the face. These warts are best treated with topical retinoids. Immunotherapies are being developed.

Bismuth↗
PubMed1990

[The population incidence of warts].

Viral warts incidence and morbidity structure were analyzed basing on the records of consultations (a total of 30,518 subjects) and the results of purposeful check-ups of various patient populations (altogether 20,020 subjects) in the town of Tomsk. The incidence of viral warts was found to be much higher (12.94%) than it is acknowledged (2.82%). Age- and to a certain measure sex-specific predisposition to viral warts are known to exist. The condition is the most incident in subjects aged 20-29; in women the peak of the incidence is recorded in younger age than in men. Students rank first in the social structure of patients suffering from this condition, schoolchildren, second. Warts of the soles occur two times more frequently than vulgar warts. Children and adolescents more often have vulgar warts, particularly boys. Vulgar warts are the most incident in children aged 10-14, sole warts in those aged 20-29.

Age Factors↗
PubMed1989

An audit of wart treatment in a Scottish dermatology department.

We measured a dermatology department's workload from wart treatment in terms of time and numbers, and we studied the use made of routine treatments according to the site of the warts and the age of the patient. Twenty-one per cent of new referrals were for warts and 19% of clinic time was used for wart treatment, 9% of clinic time was for plantar warts alone and 29.5% of new patients failed to attend. Overall cryotherapy was the commonest treatment, particularly for warts on the hands and face, 73.2% of patients treated for hand warts defaulted from follow-up and 11.3% were referred back for further treatment. The implications of the results are discussed and we argue that hospital budget holders should fund community-based wart treatment facilities.

Dermatology↗
PubMed1978

Decreased T cell levels in patients with warts.

Thymus-derived lymphocyte (T cell) levels were determined in 72 healthy patients who had viral warts, in 21 healthy patients who had been cured of warts from one to 15 years previously, and in 35 age-matched normal controls who had no history of warts. The mean percentage of lymphocytes that formed rosettes with sheep erythrocytes was less in patients with warts and patients previously cured of warts than in normal controls (P less than .001 and P less than .001, respectively). The number of total T cells/cu mm was decreased in untreated patients with warts (P less than .01) but was normal in patients cured of warts for more than one year. In addition, the morphology of the rosettes in the two patient groups differed from the controls; 32% had small numbers of sheep erythrocytes bound loosely to T cells compared with a rosette of numerous erythrocytes closely adherent to the T cell in 91% of the controls. The results suggest a defect of cellular immunity in many healthy patients with warts.

Adult↗
PubMed1996

Prevalence and risk factors for warts among slaughterhouse workers.

This study was conducted in three animal slaughterhouses in Asir Province, southern region, Saudi Arabia. The aim of this work was to determine the prevalence of warts among the workers of slaughterhouses and to identify possible risk factors of developing warts associated with work environment and workers' characteristics. Data were collected through interview questionnaire and clinical examination. The questionnaire included items on socio-demographic, occupational and clinical characteristics of the workers. Descriptive statistics, bivariates statistics and multivariate logistic regression model were used in data analysis. All 71 workers were males with a mean age of 37 +/- 9.7 years. The overall prevalence of warts was 42.2%. Heavily exposed workers had a higher prevalence (54%) (P = 0.02). Workers with other skin lesions were at a higher risk of developing warts (OR = 4.3, 95% C.I. 1.6-11.7). It was found that exposure to meat might be necessary for development of warts. Working environment could facilitate the development and transmission of warts among slaughterers. Regular monitoring of workers with skin lesions other than warts was recommended. Workers with recurrent warts were recommended to be reassigned for jobs with lighter exposure.

Abattoirs↗
PubMed1977

Recovery processes during regression of plane warts.

The regressing process of plane warts can be divided into two phases: initial changes of wart virus-infected cells that later result in degeneration of warts, and recovery phase in which degenerating warts are rejected from the level of the basal layer followed by regeneration of normal epidermal cells from the surrounding epidermis. Electron microscopic observations of recovery phase of wart regression showed (1) the epidermal lesion was clearly divided into degenerating wart possessing altered viruses and regerating epidermis; (2) melanocytes were demonstrated in degenerating warts; and (3) a new granular layer was evident beneath regressing wart in late recovery. Throughout the recovery process, infiltration of lymphocytes and macrophages was observed only in regenerating epidermis.

Adult↗
PubMed1998

Safety and efficacy of 0.5% podofilox gel in the treatment of anogenital warts.

OBJECTIVE: To determine the safety and efficacy of a new gel formulation of podofilox in the treatment of anogenital warts. DESIGN: Double-blind, randomized, multicenter, vehicle-controlled investigation. SETTING: Private dermatology practices, university clinics (dermatology, gynecology, and infectious diseases), and contract research organizations. PATIENTS: Three hundred twenty-six patients with anogenital warts. MAIN OUTCOME MEASURE: Number of patients with clearing of all treated warts (treatment success). RESULTS: The 0.5% podofilox gel was significantly better than vehicle gel for successfully eliminating and reducing the number and size of anogenital warts. In the intent-to-treat population, 62 (37.1%) of 167 patients treated with 0.5% podofilox gel had complete clearing of the treated areas (treatment successes) compared with 2 (2.3%) of 86 patients who had clearing of warts with the vehicle gel (P < .001) after 4 weeks. Nineteen additional patients treated with 0.5% podofilox gel and 2 patients treated with vehicle gel had clearing of warts with continued treatment up to 8 weeks. After 8 weeks, 35.9% of the baseline anogenital warts treated with 0.5% podofilox gel remained; this was significantly fewer than in the vehicle-treated group (88.4% of the baseline number) (P = .001). The 0.5% podofilox gel was generally well tolerated, with predominantly mild or moderate local adverse reactions occurring in the majority of patients. Only 7 patients (3.2%), all receiving 0.5% podofilox gel, discontinued study treatment because of drug-related local reactions. CONCLUSIONS: The results demonstrated that 0.5% podofilox gel is safe and significantly more effective than vehicle gel in the treatment of anogenital warts.

Administration, Cutaneous↗
PubMed1998

Mechanism of action of imiquimod 5% cream in the treatment of anogenital warts.

Objective: The objective of this randomized, double-blind, placebo-controlled trial was to evaluate the mechanism of action of imiquimod cream in the treatment of anogenital warts, and to apply the findings to the results of previously conducted safety and efficacy trials.Methods: Imiquimod (16 patients) or placebo (3 patients) cream was applied 3 times a week for up to 16 weeks; cream remained on the skin overnight for 8 +/- 2 hours. Wart biopsies were taken at prestudy, week 6, and the end of treatment (just prior to clearance or at week 16) and analyzed using PCR for HPV/DNA and RT-PCR for mRNA to identify cytokines, cellular markers, markers of proliferation and differentiation, and viral gene products. Efficacy was assessed based on wart area regression as documented by wart area measurements and photographs.Results: All patients enrolled in the trial had HPV type 6/11. All imiquimod-treated patients experienced a >/=75% clearance in baseline/target wart area. Imiquimod treatment stimulated significant increases in mRNA for IFN-alpha, 2'5' AS and IFN-gamma. Increases in mRNA for CD4, CD8, and TNF-alpha were also observed, suggesting activation of a T-helper type-1 cell mediated response. During the trial one of the vehicle treated patients also experienced spontaneous wart clearance; comparisons of the cytokine levels for this patient were similar to those observed for the imiquimod treated patients.Conclusions: The results of this mechanism of action trial indicate that the stimulation of local cytokines and cellular infiltrates by imiquimod leads to a reduction of HPV types 6 and 11 viral load with subsequent wart regression and normalization of keratinocyte proliferation without evidence of scarring. In two previous randomized vehicle-controlled trials evaluating patients with anogenital warts, the majority of patients had HPV-DNA types 6 or 11 as assessed by in situ hybridization. These results provide additional insight into the mechanism of total clearance for these otherwise healthy patients. The Th1 response demonstrated in this trial also explains the lower total clearance rates demonstrated in HIV-positive and AIDS patients.

Journal Article↗
PubMed1999

A randomized, controlled, safety study using imiquimod for the topical treatment of anogenital warts in HIV-infected patients. Imiquimod Study Group.

OBJECTIVE: To assess the safety of imiquimod, an immune response modifier, in the topical treatment of external anogenital warts in HIV-infected patients. SETTING: Clinical sites in the United Kingdom (eight) and the United States (five). DESIGN: A prospective, randomized, double-blind, vehicle-controlled study of imiquimod 5% cream or vehicle applied for 8+/-2 h three times per week for a maximum of 16 weeks in HIV-seropositive males (n = 97) and females (n = 3) aged 18 years or more with clinically diagnosed external anogenital warts, CD4 T lymphocyte count of > or = 100 x 10(6) cells/l and Karnofsky score > or = 70. MAIN OUTCOME MEASURES: Safety was assessed through the incidence and severity of local skin reactions and other adverse events, and through clinical laboratory tests. Wart clearance was documented by two-dimensional measurements of warts and by photography. RESULTS: Among the patients treated with imiquimod (n = 65) and vehicle (n = 35), the most common local skin reaction was erythema, (41.9 and 26.7%, respectively) and the incidence of patients reporting at least one adverse event was 69.2 and 65.7%, respectively. No clinically meaningful differences or changes in laboratory values were observed between treatment groups, nor were drug-related adverse effects observed in regard to HIV disease. While there was no significant difference between treatment groups in the number of patients who totally cleared their baseline warts (imiquimod 11% versus vehicle 6%, P = 0.488), more imiquimod-treated patients experienced a > or = 50% reduction in baseline wart area (38% versus 14%, P = 0.013). CONCLUSION: Most local skin reactions were mild and no adverse effects on HIV disease were observed. Topically applied imiquimod 5% cream reduced wart area and may have clinical utility in treating external anogenital warts in some HIV-infected patients.

Adjuvants, Immunologic↗
PubMed2002

Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma.

h-warts/LATS1 is a human homolog of the Drosophila warts tumor suppressor gene, which functions as a component of the mitotic apparatus. LATS1-deficient (Lats1(-/-)) mice have been reported to develop ovarian stromal tumors and soft tissue sarcomas. We investigated the status of the h-warts/LATS1 in 50 human soft tissue sarcomas to address its potential function as a tumor suppressor in human sarcoma development. In our RT-PCR assay, 7 (14%) (3 of 4 myxoid liposarcomas, 3 of 7 leiomyosarcomas, 1 of 9 malignant fibrous histiocytomas) of 50 sarcomas examined had no or a reduced expression of the h-warts/LATS1, indicating down-regulated gene expression. We further analyzed alterations of the h-warts/LATS1 in these seven sarcomas. Using microsatellite markers for chromosome 6q23-25.1, to which the h-warts/LATS1 is localized, an allelic loss of this locus was detected in one leiomyosarcoma, in which a missense point mutation of the h-warts/LATS1 was detected by PCR single-strand conformation polymorphism. Clusters of CpG dinucleotides in a 5' putative promoter region were hypermethylated in the other six sarcomas. Our data suggest that the molecular alterations of the h-warts/LATS1 could be of pathologic importance in human sarcomagenesis.

Base Sequence↗
PubMedDate not supplied

An audit of treatment of genital warts: opening the feedback loop.

An audit of the treatment of patients (100 men and 90 women) presenting with a first episode of anogenital warts to the Genitourinary Medicine Department at Leeds General Infirmary was performed. Treatment of patients was monitored for a period of 6 months from the time of presentation. The management of patients with genital warts lacked a clearly defined strategy and treatment was unselective and poorly monitored. Excluding patients who defaulted, at follow-up 44 (44%) men and 36 (38%) women still had genital warts at 3 months. Of those patients clear of warts at 3 months, the mean time to remission for men and women was 7.1 and 8.3 weeks respectively. Podophyllin 25% in tincture of benzoin was by far the predominant therapeutic modality used. A total of 96 (96%) men and 76 (84%) women received treatment with podophyllin. Both male and female patients had a mean of 5 treatments with podophyllin 25% (range 1-19 and 1-12 respectively). Physical methods of treatment i.e. cryotherapy and electrocautery, were underutilized, both as primary therapies and when topical agents had failed. Patients saw an average of 3 (range 1-7) doctors over the course of their treatment. Patients with warts affecting 2 or more sites, male patients with anal/perianal warts, and female patients with cervical and vaginal warts had higher failure rates from treatment at 3 months. On the basis of these findings, specific treatment protocols for the management of anogenital warts have been devised.

Adolescent↗
PubMed2001

Imiquimod for the treatment of genital warts: a quantitative systematic review.

OBJECTIVE: To review published randomised controlled trials to assess the benefit and harm of imiquimod in the treatment of external genital warts. DATA SOURCES: MEDLINE (1966 - December 2000), Cochrane Library (Issue 3, 2000) and PubMed (December 15, 2000), review articles and reference lists. REVIEW METHODS: Included studies had to be randomised trials of imiquimod, to be full published papers, and to have a comparison group. Quality of trial reporting was assessed. Relative benefit and number needed to treat were calculated for the main outcomes of wart clearance at the end of therapy, of at least 50% reduction in wart area, and of complete clearance at the end of treatment and no recurrence of warts during a follow-up period, as well as for adverse effect withdrawal or lack of efficacy withdrawal. RESULTS: There were six trials, all with quality scores of 3 (out of 5) or greater. In five trials with HIV-negative patients complete clearance of warts at the end of treatment occurred in 51% of patients treated with imiquimod 2% or 5% cream and 6% of placebo treated patients. The number needed to treat was 2.2 (95% confidence interval 2.0 to 2.6). In four trials at least 50% wart area reduction occurred with 72% of patients treated with imiquimod 5% cream and 20% of placebo treated patients. The number needed to treat was 1.9 (1.7 to 2.2). In three trials complete clearance of warts at the end of treatment plus no recurrence occurred in 37% of patients treated with imiquimod 5% cream and 4% of those treated with placebo. The number needed to treat was 3.0 (2.5 to 3.8). Adverse event withdrawal was rare and no more likely with imiquimod than with placebo. Imiquimod was not effective in one trial in HIV-positive patients. CONCLUSION: The evidence base for imiquimod in treating genital warts is of high quality and the necessary size from which to draw useful conclusions. Imiquimod is effective in home application, though not in patients with HIV infection with the evidence presently available.

AIDS-Related Opportunistic Infections↗
PubMed1998

An international survey of patients with genital warts: perceptions regarding treatment and impact on lifestyle.

Our aim was to determine country-specific attitudes and perceptions of patients with genital warts and to understand the psychosexual impact of the disease and its treatment. We used a standardized discussion guide to interview patients with genital warts in Canada, France, Germany, the UK, and the USA about their perceptions and concerns regarding the diagnosis, treatment, and psychosexual impact of the disease. Interviews were conducted in person and lasted approximately 30 min. The study group included 80 men and 86 women with genital warts. Forty-seven per cent were currently undergoing treatment. Overall, 49% of the men had first consulted a general or family practitioner, and 52% of the women had first consulted a gynaecologist. Although all the patients eventually consulted a physician about their warts, one-third delayed seeing a doctor because they thought the condition would resolve on its own or that the problem was not serious. Most patients reported that treatment was associated with pain, discomfort, and embarrassment. Sixty per cent of patients experienced a recurrence after initial clearance with treatment. More than 80% stated that they had had little or no involvement in the selection of treatment. Globally, 52% of men and 61% of women were 'quite concerned' or 'very concerned' about having genital warts, although there were significant variations by country. Approximately two-thirds of patients had made lifestyle changes regarding sexual relationships. In addition, two-thirds believed that there were risks associated with having genital warts; the most common risk identified was a link to cancer (cervical and unspecified). A high level of anxiety is associated with the diagnosis and treatment of genital warts. Patients with genital warts require understanding and an acknowledgement of their concerns. A better understanding of the psychosexual aspect of the disease by health-care providers is pivotal to effective disease management and patient counselling.

Adolescent↗
PubMed1998

Comparing treatment response and complications between podophyllin 0.5%/0.25% in ethanol vs podophyllin 25% in tincture benzoin for penile warts.

AIM: The aims of this study were to: 1) ascertain if podophyllin resin in 0.5% [PE(0.5%)] and 0.25% [PE(0.25%)] in ethanol (PE) self-applied sequentially for 3 days with 4 days break cycle is as effective as supervised podophyllin 25% in tincture benzoin (PB) applied in the clinic biweekly in treating penile warts and 2) ascertain if PE causes less skin irritation than PB. METHODS AND RESULTS: The clearance rate of penile warts was 36.4% (4/11) in PE (0.5%) treated group, 66.7% (4/6) in the PE (0.25%) treated group and 33.3% (6/18) for PB treated group after 1 week (ns). The wart clearance rate at 6 weeks for PE (0.5%) treated group, PE (0.25%) treated group and PB treated group were 81.8% (9/11), 100% (6/6) and 83.3% (15/17) respectively (ns). There were 47 individual warts on the penis of the 17 patients in the PE treated group and 58 individual warts on the penis of the 18 patients in the PB treated group. Based on the response of individual warts to the 2 treatment regimens, the clearance rate was 42.6% (20/47) for the PE treated group and 25% (15/56) for the PB treated group after 1 week treatment (ns). At 6 weeks follow-up, the clearance rate for the PE treated group and the PB treated group were 85.1% (40/47) and 73.2% (41/56) respectively (ns). Skin irritation including superficial erosions, pain and itch were observed in 47% (8/17) in patients treated with PE compared to 38.9% (7/18) in patients treated with PB (ns) during the 6 weeks follow-up period. The clearance rate of patients treated with PE (0.25%) was compared to those treated with PE (0.5%). Four out of six of PE (0.25%) treated patients had clearance of warts after 1 week and 100% clearance at the end of 6 weeks. None experienced any skin irritation. CONCLUSION: This study demonstrates that 0.5% podophyllin (and possibly 0.25% podophyllin) in ethanol is effective in eradicating penile warts. It can be used by patients for self-treatment at home with greater convenience and is more cost effective than the conventional podophyllin 25% in tincture benzoin paint.

Adult↗
PubMed2026

Molecular insights and therapeutic innovations in low-risk human papillomavirus-associated cutaneous wart.

Human papillomavirus (HPV) is a DNA virus that belongs to the Papillomaviridae family. Among the various types, high-risk strains are associated to malignancy, whereas low-risk types cause benign skin warts due to persistent infection. Unlike high-risk HPVs, low-risk HPV genomes remain in an episomal state while expressing E6/E7 proteins. These proteins exhibit a reduced ability to degrade pRb and p53, which finally leads to controlled epithelial hyperplasia instead of developing malignancy. Infection with low-risk HPV activates distinct host signaling pathways, ultimately promoting the proliferation of keratinocytes and formation of warts. Simultaneously, it triggers host innate and adaptive immune responses that often clear the lesion. This review focuses on low-risk types that cause skin warts by analyzing the molecular pathways, particularly the integrin-FAK-PI3K/AKT, Hippo-YAP/TAZ pathway along with MAPK-ERK pathways that promotes cutaneous benign wart formation. This article further studies clinical management strategies for HPV associated warts, including primary destructive treatment (cryotherapy, keratolytics, excision), immunotherapies (imiquimod, interferon injections or intralesional antigen), and novel adjunctive therapies with clinical evidence including photodynamic therapy, intralesional chemotherapeutics, and emerging HPV vaccination strategies. Among these, for benign skin warts, intralesional immunotherapy, particularly Candida antigen, and intralesional HPV vaccination have shown encouraging responses clinically. But extensive controlled clinical studies are necessary to establish their efficacy and clinical value as a standard medicine. This review therefore, generates a comprehensive overview of papilloma virus mediated skin warts and their management for both clinicians and researchers.

Humans↗