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PubMed1982

Plantar warts recently turned black. Clinical and histopathologic findings.

The inflammatory component associated with blackening and subsequent regression of plantar warts has been little appreciated in the literature. Two patients with plantar warts in whom one of the warts showed prominent, clinically evident inflammation were observed. Blackening and subsequent regression of all plantar warts then occurred. In one patient, microscopic examination of biopsy specimens of two lesions that were taken within 24 and 72 hours, respectively, after they had turned black demonstrated the following histologic findings: blood clots and hemorrhage in the stratum corneum, degeneration and necrosis of epidermal cells, eosinophilic cytoplasmic masses within degenerating epidermal cells, thrombosis of superficial and deeper dermal blood vessels, a mononuclear cell infiltrate in and around dermal blood vessels, and a mixed polymorphonuclear and lymphocytic infiltration in the areas of hemorrhage and degenerating epidermis. This constellation of histopathologic changes suggests that involution was in progress long before blackening of the warts occurred.

Administration, Topical↗
PubMed1977

Levamisole in a double-blind study: no effect on warts.

Levamisole is reported to restore delayed hypersensitivity, when this is depressed. On the assumption that multiple warts, resistant to local treatment, are indicative of some immune deficiency, we chose levamisole for the treatment of warts. The dose, 150 mg daily in 3 days every second week, was given to 49 patients who had common warts and to 50 patients who had condyloma (venereal warts). After 6 weeks of double-blind study, most of the patients underwent open levamisole treatment. However, the levamisole group failed to show enhanced wart regression compared with the control group. No inter-group difference could be detected as regards change in delayed hypersensitivity after levamisole treatment, when measured by the mantoux response.

Adolescent↗
PubMed1977

Spontaneous regression of plane warts after inflammation: clinical and histologic studies in 25 cases.

Based on clinical and histological studies in 25 patients, we have confirmed that plane warts show a characteristic phenomenon of spontaneous regression totally distinct from that described in common warts. This regression developed during various treatments in nine cases, and in 16 cases, it occurred spontaneously. In all the patients, there was a sudden and systemic onset of inflammation in every flat wart. Within two to six weeks, all the warts completely involuted. Histologically, there were variable degrees of epidermal changes depending on the stage of inflammation. However, a mononuclear cell infiltration with epidermal invasion was demonstrated in every biopsy specimen. This evidence further supports the earlier concept that this regressive phenomenon of plane warts is mediated by cellular immunity. It represents a natural experimental model of rejection of tumors induced by papovavirus in humans.

Adolescent↗
PubMed1995

Human immunodeficiency virus infection and genital warts as risk factors for anal intraepithelial neoplasia in homosexual men.

The incidence of anal intraepithelial neoplasia (AIN) was studied in a group of 210 homosexual and bisexual men. The presence of genital warts and human immunodeficiency virus (HIV) infection was assessed as risk factors for the development of AIN. In all, 74 (35 per cent) of the group had histological evidence of AIN. The relative risk of being positive for HIV on AIN (relative to being negative for HIV) was 1.58 (95 per cent confidence interval (c.i.) 1.01-2.48). The relative risk of anal warts on AIN (relative to absence of anal warts) was 4.70 (95 per cent c.i. 1.81-12.20). Logistic regression analysis showed no significant interactive effect between HIV and anal warts on the risk of AIN. It is concluded from the results of a Mantel-Haenzel analysis that the presence of anal warts and HIV infection are independent risk factors for the development of AIN in homosexual and bisexual men.

Anus Diseases↗
PubMed1995

Upregulation of integrin expression in benign vulvar warts.

Benign anogenital warts demonstrate features both of hyperproliferation and of aberrant differentiation associated with human papillomavirus (HPV) infection. The expression of integrins has been examined in normal vulvar epithelium and benign vulvar warts to determine whether HPV infection is associated with changes in integrin expression, either during terminal differentiation or among the proliferating cell population. The expression of integrins in normal vulvar epithelium was similar to that seen in the epidermis, with little expression of alpha 1 and expression of alpha 2, alpha 3, and beta 1 at the periphery of basal cells. In vulvar wart epithelium, alpha 1 was not significantly expressed, but upregulation of alpha 2, alpha 3, and beta 1 was seen at the periphery of cells throughout the basal and spinous layers. In addition, alpha 2 staining was greater at foci along the basal layer of normal vulva, whilst such heterogeneity was not detected in wart sections. Expression of beta 4 and alpha V was confined to the basal and lateral aspects of normal basal cells, but expressed at the periphery of basal cells and to a lesser extent in epibasal and spinous layers of warts. The observed differences in integrin expression are consistent with those reported in other hyperproliferative epithelia.

Condylomata Acuminata↗
PubMed1990

Intralesional interferon alfa-2b for the treatment of genital warts.

A randomized, double-blind, placebo-controlled study has been conducted, and intralesional interferon alfa-2b was tested in the treatment of genital warts. This study design was to give 1 million units interferon alfa-2b intralesionally into the base of each of five external genital warts per patient, on a Monday-Wednesday-Friday treatment schedule for 3 weeks (total of nine injections). Forty-two patients were entered (20 randomized to receive interferon and 22 placebo injections). There were 43.8% of patients on the interferon treatment arm of the double-blind portion of the study who had complete disappearance of all warts, with an additional 25% of patients showing greater than 50% shrinkage of visible warts. On the placebo arm 14.3% showed a complete response, with an additional 14.3% showing greater than 50% shrinkage. This difference between interferon and placebo treatment was statistically significant (p less than 0.03). We conclude that intralesional interferon alfa-2b has significant activity in the treatment of genital warts.

Adolescent↗
PubMed2004

Effect of antiretroviral therapy on the incidence of genital warts and vulvar neoplasia among women with the human immunodeficiency virus.

OBJECTIVE: The purpose of this study was to determine the incidence and predictors of genital warts and vulvar intraepithelial neoplasia among women with the human immunodeficiency virus. STUDY DESIGN: This was a multicenter prospective cohort study comprised of women without warts or vulvar intraepithelial neoplasia at baseline who underwent CD4 count, human immunodeficiency virus RNA measurement, examination, Papanicolaou test, and biopsy, as indicated, every 6 months. Human papillomavirus DNA typing was examined at baseline. RESULTS: The incidence of warts among women who were human immunodeficiency virus seronegative was 1.31 versus 5.01 per 100 person-years among women who were seropositive (P < .001). Incidence of vulvar intraepithelial neoplasia among women who were seronegative was 1.31 versus 4.67 per 100 person-years among women who were seropositive (P < .001). In multivariable analysis, warts were associated with highly active antiretroviral therapy (relative hazard, 0.76), CD4 count (relative hazard, 0.91/100 cell/cm(2) increase), acquired immunodeficiency syndrome (relative hazard, 1.25), abnormal Papanicolaou test results (relative hazard, 2.18), high- or medium-risk human papillomavirus types (relative hazard, 1.91), low-risk human papillomavirus types (relative hazard, 1.48), smoking (relative hazard, 1.43), having 1 child (relative hazard, 1.54), and age (relative hazard, 0.74/10 years). Vulvar intraepithelial neoplasia was linked to highly active antiretroviral therapy (relative hazard, 0.65), CD4 count (relative hazard, 0.92), abnormal Papanicolaou test results (relative hazard, 16.03), high- or medium-risk human papillomavirus types (relative hazard, 1.37), and age (relative hazard, 0.85/10 years). CONCLUSION: Warts and vulvar intraepithelial neoplasia are common among women with human immunodeficiency virus. Highly active antiretroviral therapy decreases their incidence.

Adult↗
PubMed1997

Therapeutic approaches to genital warts.

Although many treatments are available for genital warts caused by human papillomavirus (HPV), none are uniformly successful in the treatment of this disease. Most current treatment options work by destroying affected tissue, either by a cytotoxic or a physically ablative mode of action. Interferons have antiviral, antiproliferative, and immunomodulatory activities, but these have not translated into a high level of cure rates against warts. With all current treatments, recurrent warts are common. Therapies currently being investigated include a 5-fluorouracil/epinephrine collagen gel that achieves high concentrations of 5-fluorouracil at the site of injection. Other new treatment modalities focus on activating the host's immune system or improving the delivery of therapeutic compounds to the affected site. Imiquimod, a novel immune-response modifier, induces interferon and a number of other endogenous cytokines. A cream formulation containing 5% imiquimod resulted in good total clearance rates and generally tolerable side effects in controlled clinical trials of patients with external genital warts. Perhaps the most effective means for managing HPV disease would be a vaccine that prevents the occurrence of genital warts. Although it is unlikely that such a vaccine will be introduced in the near future, preliminary studies indicate that it may be possible to develop suitable prophylactic and therapeutic vaccines.

Adjuvants, Immunologic↗
PubMed2005

[Efficacy and safety of 5% imiquimod cream in external genital warts: a 6 month follow-up evaluation].

INTRODUCTION: One of the main issues raised by the management of external genital warts is their potential risk of recurrence. However, nearly all studies assessing recurrences have been conducted with a 3 month follow-up. Since the latency of the human papillomavirus is long, such 3 month follow-up might be too short to detect the true recurrence rate. We therefore conducted a study evaluating patients with external genital warts, treated with an immune response modifier, 5% imiquimod cream, and followed up to 6 months after total clearance. METHODS: This was an open, non comparative, multicenter study conducted in 51 private or hospital practices in France. 5% imiquimod cream was applied 3 times per week until the clearance of external genital warts, with a maximum application period of 16 weeks. Patients were followed-up for 6 months after complete clearance. RESULTS: One hundred ninety-one patients (103 males and 88 females), with a mean age of 31.4 years (18.1-70.4) were included in this study, between November 29 1999 and February 1st 2001. Complete clearance of external genital warts was noted in the ITT analysis in 103/191 cases (54 p. 100; CI95 p. 100: 40-61). Fifteen out of 92 (16 p. 100; CI95 p. 100: 9.4-25.5) had a recurrence within the 6 months follow-up period, 13 of these 15 recurrences were noted at the 3 month follow-up visit. CONCLUSION: The rate of recurrence of external genital warts at 6 months was similar to the rate noted at 3 months, suggesting that after the 3-month period, the risk of developing a recurrence was low. The mode of action of imiquimod through the induction of cytokines and the stimulation of the local immune response could explain these results.

Adjuvants, Immunologic↗
PubMed1988

Colposcopic evaluation of men with genital warts.

Colposcopy, which is the examination of the female genital tract that generally is performed after the application of acetic acid, has been an effective tool in the diagnosis of genital warts (condyloma acuminatum) in women for years. With the help of colposcopy, both microscopic and flat warts that cannot be visualized with traditional, noncolposcopic methods can be seen and, hence, treated. Recently, studies reported in the gynecologic and urologic literature have evaluated the usefulness of colposcopy in male patients. We present a patient whose genital warts were recalcitrant to treatment. When examined with colposcopy he was noted to have multiple additional areas of involvement. In view of the neoplastic potential of the human papillomavirus, the ease with which it is transmitted sexually, and the difficulty in discerning certain kinds of warts without colposcopy, we believe colposcopic examination should be routine in all men with genital warts and in those whose sexual partners have tested positive for human papillomavirus.

Adult↗
PubMed2006

Treatment of genital warts in males by pulsed dye laser.

OBJECTIVE: To determine the safety and efficacy of the flashlamp-pumped pulsed dye laser for the treatment of uncomplicated genital warts in adult males. METHODS: This was a prospective observational study set in the outpatient clinics of the Department of Andrology and Sexually Transmitted Diseases, National Institute of Laser Enhanced Sciences, the Dermatology Clinic, Cairo University, and the Department of Dermatology and Venereology, Suez Canal University. A total of 174 adult male patients with 550 uncomplicated anogenital warts were included. Selective photothermolysis and photocoagulation of the lesions with the flashlamp-pumped pulsed dye laser was carried out. A pulsed dye laser (wavelength 585 nm, 450 s pulse duration; Cynosure, USA) was used with the following settings: spot size 5-7 mm; fluence 9-10 J/cm2. RESULTS: Complete resolution of treated warts was achieved in 96% of lesions. Side effects were limited, transient and infrequent. Lesion recurrence rate was 5%. CONCLUSION: The pulsed dye laser has been found to be safe, effective and satisfactory for the treatment of anogenital warts in males. It could be used to selectively destroy warts without damaging the surrounding skin.

Adult↗
PubMed2003

The health and economic burden of genital warts in a set of private health plans in the United States.

We estimated the prevalence of and costs associated with genital warts among privately insured individuals from the perspective of a private health plan in the United States. Health care claims data were derived from a sample of 3,664,686 privately insured individuals. The database was limited to cases of disease for which an insurance claim was generated, with costs reflecting inpatient, outpatient, and pharmacy payments from all sources. We identified 5095 cases of genital warts (1.7 cases per 1000 person-years) billed through the health plans during 2000. The prevalences of and health plan costs associated with genital warts were highest among women aged 20-24 years (6.2 cases and $1692 in costs per 1000 person-years) and men aged 25-29 years (5.0 cases and $1717 in costs per 1000 person-years). On average, individual episodes of care for genital warts involved 3.1 physician visits and incurred costs of $436. These are the first age- and sex-specific estimates of the prevalence and cost of genital warts for a US health plan.

Condylomata Acuminata↗
PubMed2004

Using imiquimod for genital warts in female patients.

Genital warts (GW) are the manifestation of infection with specific types of human papillomavirus (HPV), one of the most common sexually transmitted viral infections in the world. Genital warts can be either raised (exophytic) or flat. Exophytic genital warts are most commonly secondary to inoculation of the basal epithelium with nononcogenic HPV types 6 and 11, whereas flat warts are usually secondary to potentially oncogenic HPV types 16 and 31. Genital warts can occasionally cause irritation and discomfort, particularly during intercourse, although most cases are asymptomatic. It is the psychosocial effects of infection, such as a sense of shame, depression, and anxiety, that represent the more significant toll for most patients with GW. Current therapies for GW are mainly ablative and do not directly enhance the immune response to HPV. Therefore, recurrence is a problem for many patients. Imiquimod 5% cream is a patient-applied therapy that directly enhances the immune response to HPV and is safe and effective for the treatment of GW. A reduction in viral load is observed following treatment. Low recurrence rates compared to other treatment modalities may be due to the stimulation of the cell-mediated immune response by imiquimod.

Administration, Topical↗
PubMed1994

Immunological events in regressing genital warts.

Little is known of the in vivo role of the immune system in controlling human papillomavirus infection in the genital tract. The authors have studied 125 closely monitored patients with genital warts. Of these 125 patients, wart regression was seen in 28 patients. This study provides evidence that clearance of human papillomavirus from the genital tract is characterized by an active cell-mediated immune response. Regressing warts (n = 14) contained significantly more T lymphocytes (P < .05, Wilcoxon rank sum test) and macrophages (P < .01) than did nonregressing controls (n = 14). CD4-positive lymphocytes predominated in regression, both within the wart stroma and the surface epithelium, where there was a significant change in the ratio of CD4+ to CD8+ cells (P < .01). Lymphocytes in regression also showed greater expression of activation markers, and the majority were of the "antigen-experienced" phenotype. There was no difference in Langerhans cell numbers, although there was significant induction of the immune accessory molecules HLA-DR and ICAM1 (P < .05) on keratinocytes, and E-selectin and VCAM1 (P < .05) on endothelial cells in regressing warts. The changes in regression are consistent with a delayed-type hypersensitivity reaction to foreign antigen, and the ability to induce and mount such a response may be a critical determinant of effective natural immunity to the genital HPVs. Specific targeting of delayed-type hypersensitivity responsiveness may increase the efficacy of strategies for immuno-intervention against HPV infection in the genital tract.

Adult↗
PubMed1995

Human papillomavirus infection and genital warts: update on epidemiology and treatment.

The treatment of genital warts remains frustrating since it is often painful, expensive, and unsuccessful. Moreover, little is known about the infectivity and natural history of exophytic genital warts or subclinical genital infection with human papillomavirus. The traditional goals of therapy for sexually transmitted diseases--eradication of infection, elimination of symptoms, prevention of long-term sequelae, and interruption of transmission--are currently not attainable for or applicable to genital warts. The medical literature from January 1988 to August 1993 was reviewed for recent studies on the treatment of exophytic warts. The following treatments were included in the reviewed studies: podofilox (which was recently approved by the Food and Drug Administration), podophyllin, cryotherapy, topical 5-fluorouracil, intralesional interferon, systemic interferon, and laser surgery. No single treatment modality was superior to another, and recurrence rates associated with all modalities were high. Treatment of genital warts should be guided by preferences of the patient, and a specific therapeutic regimen should be chosen with consideration of expense, efficacy, convenience, and potential for adverse effects.

Condylomata Acuminata↗
PubMed1990

A randomized trial of combination therapy with intralesional interferon alpha 2b and podophyllin versus podophyllin alone for the therapy of anogenital warts.

To determine the value of combining interferon with standard local therapy in the treatment of human papillomavirus infection, 97 patients with anogenital warts were randomized to a short course of either interferon plus podophyllin or podophyllin alone. Interferon alpha 2b (1.5 x 10(6) IU) was injected intralesionally and podophyllin resin applied topically to each of three warts once weekly for 3 weeks. Maximal responses occurred within 2 weeks of therapy, and overall there was complete clearance of treated warts in 67% of interferon and podophyllin versus 42% of podophyllin recipients (P less than .05, chi 2). Clearance rates were greater in women, patients with warts of less than or equal to 12 months' duration, and HIV-seronegative patients. Of patients with complete clearance, 67% of interferon and podophyllin and 65% of podophyllin recipients experienced recurrences. Thus, in short treatment courses of anogenital warts, intralesional interferon enhanced the effect of topical podophyllin, and trials of combination therapy using more intensive or prolonged regimens of interferon are warranted.

Administration, Topical↗
PubMed2001

Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day.

BACKGROUND: Medical therapy for genital warts remains suboptimal. The topical interferon and cytokine inducer, imiquimod, has been proved effective for the treatment of external genital and perianal warts, but there is a substantial difference in the response rates between men and women. When 5% imiquimod cream is applied three times a week up to 16 weeks, approximately two thirds of women treated with imiquimod achieve complete clearance of genital warts, whereas only about one third of men clear completely. GOAL: This study was undertaken to determine whether more frequent application of topical imiquimod cream would improve the rate of genital wart clearance in men. STUDY DESIGN: A randomized treatment trial involving adult men with biopsy-proven genital warts was conducted at nine centers in the United States and Canada using four different application frequencies. RESULTS: Complete clearance rates during the 16-week treatment period were as follows for the different imiquimod treatment frequencies: three times a week (35 %), once daily (28 %), twice daily (24%), and three times a day (27%)(P = 0.88). The four treatment groups all showed comparable reductions in the total lesion area, with a median of more than a 90% reduction in the lesion area by the end of treatment. There was a significant increase in the incidence and severity of local skin reactions including erythema, vesicle formation, ulceration, and excoriation as the dosing frequency increased from three times a week to three times a day. CONCLUSIONS: In this study, the optimal dosage regimen was the approved three times a week regimen. More frequent application (up to three times a day) did not improve clearance and was associated with an increase in local adverse events.

Adult↗
PubMed2002

The impact of HIV infection and immunodeficiency on human papillomavirus type 6 or 11 infection and on genital warts.

BACKGROUND: HIV infection and associated immunodeficiency are known to alter the course of human papillomavirus (HPV) infections and of associated diseases. GOAL: This study investigated the association between HIV and HPV and genital warts. STUDY DESIGN: HPV testing and physical examinations were performed in two large prospective studies: the Women's Interagency HIV Study (WIHS) and the HIV Epidemiology Research Study (HERS). Statistical methods incorporating dependencies of longitudinal data were used to examine the relationship between HIV and HPV and genital warts. RESULTS: A total of 1008 HIV-seronegative and 2930 HIV-seropositive women were enrolled in the two studies. The prevalence of HPV 6 or 11 was 5.6 times higher in HIV-seropositive women in the WIHS and 3.6 times higher in the HERS. Genital wart prevalence increased by a factor of 3.2 in the WIHS and 2.7 in the HERS in HIV-seropositive women. In the WIHS, infection with HPV type 6 or 11, in comparison with no HPV infection, was associated with odds of genital wart prevalence of 5.1 (95% CI: 2.9-8.8), 8.8 (95% CI: 6.1-12.8), and 12.8 (95% CI: 8.8-18.8) in HIV-seronegative women, HIV-seropositive women with > or =201 CD4 cells/microl, and HIV-seropositive women with < or =200 CD4 cells/microl, respectively. In the HERS, infection with HPV type 6 or 11 was associated with odds of 2.7 (95% CI: 1.6-4.6), 4.9 (95% CI: 3.2-7.7), and 5.3 (95% CI: 3.3-8.5) in these same groups. Other HPV types showed a similar dose-response relation, but of substantially lower magnitude and statistical significance. CONCLUSIONS: HIV infection and immunodeficiency synergistically modified the relation between HPV 6 or 11 infection and genital wart prevalence.

AIDS-Related Opportunistic Infections↗