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The incidence of primary cutaneous melanoma has been increasing dramatically for several decades. Melanoma accounts for the majority of skin cancer–related deaths, but treatment is nearly always curative with early detection of disease. In this update of the guidelines of care, we will discuss the treatment of patients with primary cutaneous melanoma. We will discuss biopsy techniques of a lesion clinically suspicious for melanoma and offer recommendations for the histopathologic interpretation of cutaneous melanoma. We will offer recommendations for the use of laboratory and imaging tests in the initial workup of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, we will provide recommendations for surgical margins and briefly discuss nonsurgical treatments. Finally, we will discuss the value and limitations of sentinel lymph node biopsy and offer recommendations for its use in patients with primary cutaneous melanoma.

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In the first 5 parts of the AmericanAcademy of Dermatology Psoriasis Guidelines of Care, we have presented evidence supporting the use of topical treatments, phototherapy, traditional systemic agents, and biological therapies for patients with psoriasis and psoriatic arthritis. In this sixth and final section of the Psoriasis Guidelines of Care, we will present cases to illustrate how to practically use these guidelines in specific clinical scenarios. We will describe the approach to treating patients with psoriasis across the entire spectrum of this fascinating disease from mild to moderate to severe, with and without psoriatic arthritis, based on the 5 prior published guidelines. Although specific therapeutic recommendations are given for each of the cases presented, it is important that treatment be tailored to meet individual patients' needs. In addition, we will update the prior 5 guidelines and address gaps in research and care that currently exist, while making suggestions for further studies that could be performed to help address these limitations in our knowledge base.

Background Evidence-based clinical guidelines are developed to educate and inform physicians about best practices in patient care, and assist providers in the application of treatments and technologies that can improve outcomes. Clinical guidelines also aid appeal of payment decisions; serve as the basis for quality measure development, appropriateness criteria, and maintenance of certification modules; and help identify areas for further clinical research. Objective For guidelines to serve dermatologists effectively in these diverse roles, they must be current, varied in clinical focus, and developed with a high degree of rigor that includes attention to potential conflicts of interest. Method To address these needs and keep pace with advances in medicine, the American Academy of Dermatology (AAD) recently revised the evidence-based guideline development process. Results Key changes include development of a yearly needs assessment process to determine what guidelines are most needed, the development of focused guidelines that address rapidly evolving clinical topics, a formal method of vetting guidelines produced by other societies, and a scheduled reassessment of existing guidelines to ensure they provide current and practical information. The process for identifying and managing potential conflicts of interest was also revised and expanded to meet current expectations and evolving standards. Limitations The impact of these changes to the AAD's guideline development process will not be fully realized for several years. Conclusions These changes will help ensure the AAD will be able to provide its members with continued evidence-based guidance to support patient care across the scope of dermatologic practice.

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this fifth of 6 sections of the guidelines of care for psoriasis, we discuss the use of ultraviolet (UV) light therapy for the treatment of patients with psoriasis. Treatment should be tailored to meet individual patients' needs. We will discuss in detail the efficacy and safety as well as offer recommendations for the use of phototherapy, including narrowband and broadband UVB and photochemotherapy using psoralen plus UVA, alone and in combination with topical and systemic agents. We will also discuss the available data for the use of the excimer laser in the targeted treatment of psoriasis. Finally, where available, we will summarize the available data that compare the safety and efficacy of the different forms of UV light therapy.

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this fourth of 6 sections of the guidelines of care for psoriasis, we discuss the use of traditional systemic medications for the treatment of patients with psoriasis. Treatment should be tailored to meet individual patients' needs. We will discuss in detail the efficacy and safety, and offer recommendations for the use of the 3 most commonly used, and approved, traditional systemic agents: methotrexate, cyclosporine, and acitretin. We will also briefly discuss the available data for the use of azathioprine, fumaric acid esters, hydroxyurea, leflunomide, mycophenolate mofetil, sulfasalazine, tacrolimus, and 6-thioguanine in psoriasis.

Psoriasis is a common, chronic, inflammatory, multi-system disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this third of 6 sections of the guidelines of care for psoriasis, we discuss the use of topical medications for the treatment of psoriasis. The majority of patients with psoriasis have limited disease (

To estimate the clinical efficacy of topical sinecatechins, a defined green tea extract, in the treatment of external genital and perianal warts.This was a randomized, double-blind, vehicle-controlled trial involving 502 male and female patients aged 18 years and older, with 2-30 anogenital warts ranging from 12 to 600 mm(2) total wart area. Patients applied sinecatechins ointment 15% or 10% or vehicle (placebo) three times daily for a maximum of 16 weeks or until complete clearance of all warts, followed by a 12-week treatment-free follow-up to assess recurrence.Complete clearance of all baseline and newly occurring warts was obtained in 57.2% and 56.3% of patients treated with sinecatechins ointment 15% and 10%, respectively, compared with 33.7% for vehicle (both P.001). Significance was observed at weeks 4 and 6 and all subsequent visits. Numbers needed to treat were 4.3 and 4.4. Partial clearance rates of at least 50% were reported for 78.4% and 74.0% of patients in the sinecatechins ointment 15% and 10% groups compared with 51.5% of vehicle patients. During follow-up, recurrence of any wart was observed in 6.5%, 8.3%, and 8.8% in the sinecatechins ointment 15% group, sinecatechins ointment 10% group, and vehicle patients, respectively. A total of 3.7%, 8.3%, and 0.0% developed new warts, respectively. A total of 87.7% and 87.3% of patients in the sinecatechins ointment 15% and 10% groups, and 72.1% of vehicle patients experienced application site reactions; 49.2%, 46.2%, and 65.4% of those, respectively, were mild or moderate.Topical sinecatechins ointments 15% and 10% are effective and well-tolerated in the treatment of anogenital warts.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00449982.I.

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this second of 5 sections of the guidelines of care for psoriasis, we give an overview of psoriatic arthritis including its cardinal clinical features, pathogenesis, prognosis, classification, assessment tools used to evaluate psoriatic arthritis, and the approach to treatment. Although patients with mild to moderate psoriatic arthritis may be treated with nonsteroidal anti-inflammatory drugs and/or intra-articular steroid injections, the use of disease-modifying antirheumatic drugs, particularly methotrexate, along with the biologic agents, are considered the standard of care in patients with more significant psoriatic arthritis. We will discuss the use of disease-modifying antirheumatic drugs and the biologic therapies in the treatment of patients with moderate to severe psoriatic arthritis.

Background A replication incompetent herpes virus lacking the glycoprotein H gene has been developed as a potential therapeutic vaccine for genital herpes. Goal To determine vaccine efficacy on reducing HSV reactivation and clinical disease among immunocompetent persons with recurrent genital HSV-2 infection. Study design Randomized multicenter placebo-controlled trial. Healthy volunteers who had six or more recurrences of genital herpes per year were randomized to receive injections of vaccine at 0 and 8 or 0, 4, and 8 or 0, 2, 4, and 8 weeks or placebo and were followed for subsequent recurrences for 1 year. Results The median times to first recurrence of genital herpes (40 days versus 30 days versus 37 days versus 42 days, respectively), mean number of recurrences (3 versus 3 versus 2.4 versus 1.9, respectively), and time to lesion healing of the first recurrence (8 days versus 7.8 days versus 7.4 days versus 7.5 days, respectively), were similar for all treatment groups. Asymptomatic viral shedding was detected by PCR in 61/74 (82%) persons performing daily sample collection following completion of the vaccination series. No differences were noted in the proportion of days with shedding between treatment groups (11.9% versus 17.2% versus 13.1% versus 16.4%, respectively). Conclusion This replication incompetent HSV-2 vaccine lacking the glycoprotein H gene was safe but had no clinical or virologic benefit in the amelioration of genital HSV-2 disease among immunocompetent men and women.

Nucleoside analogues against herpes simplex virus (HSV) have been shown to suppress shedding of HSV type 2 (HSV-2) on genital mucosal surfaces and may prevent sexual transmission of HSV.We followed 1484 immunocompetent, heterosexual, monogamous couples: one with clinically symptomatic genital HSV-2 and one susceptible to HSV-2. The partners with HSV-2 infection were randomly assigned to receive either 500 mg of valacyclovir once daily or placebo for eight months. The susceptible partner was evaluated monthly for clinical signs and symptoms of genital herpes. Source partners were followed for recurrences of genital herpes; 89 were enrolled in a substudy of HSV-2 mucosal shedding. Both partners were counseled on safer sex and were offered condoms at each visit. The predefined primary end point was the reduction in transmission of symptomatic genital herpes.Clinically symptomatic HSV-2 infection developed in 4 of 743 susceptible partners who were given valacyclovir, as compared with 16 of 741 who were given placebo (hazard ratio, 0.25; 95 percent confidence interval, 0.08 to 0.75; P=0.008). Overall, acquisition of HSV-2 was observed in 14 of the susceptible partners who received valacyclovir (1.9 percent), as compared with 27 (3.6 percent) who received placebo (hazard ratio, 0.52; 95 percent confidence interval, 0.27 to 0.99; P=0.04). HSV DNA was detected in samples of genital secretions on 2.9 percent of the days among the HSV-2-infected (source) partners who received valacyclovir, as compared with 10.8 percent of the days among those who received placebo (P0.001). The mean rates of recurrence were 0.11 per month and 0.40 per month, respectively (P0.001).Once-daily suppressive therapy with valacyclovir significantly reduces the risk of transmission of genital herpes among heterosexual, HSV-2-discordant couples.

External genital warts (EGWs) are visible warts that occur in the perigenital and perianal regions. They are due primarily to non-oncogenic human papillomavirus (HPV) types, usually types 6 and 11. Physical examination assisted by bright light and magnification is the recommended approach for primary diagnosis. Biopsy is indicated when EGWs are fixed to underlying structures or discolored or when standard therapies are not effective. Recurrences are common, and there is no single treatment that is superior to others. Among women with atypical squamous cells, molecular HPV testing may be useful in determining who should be referred for colposcopy. Condoms may provide some protection against HPV-related diseases and thus are recommended in new sexual relationships and when partnerships are not mutually monogamous. Because the efficacy of cesarean section in preventing vertical transmission of HPV infection from women with EGWs to their progeny has not been proved, it is not recommended.

Objective To compare the efficacy and safety of valacyclovir hydrochloride and famciclovir for the treatment of herpes zoster. Design A double-blind, randomized, controlled, multicenter clinical trial in which patients received 7 days of treatment and were followed up for 24 weeks. Settings Patients reported directly to specialist centers or were referred from primary care centers. Patients There were 597 otherwise healthy immunocompetent outpatients, aged 50 years and older, who presented within 72 hours of onset of zoster rash. Interventions Treatment with valacyclovir hydrochloride (1 g 3 times daily) or famciclovir (500 mg 3 times daily) for 7 days. Main outcome measures Resolution of zoster-associated pain and postherpetic neuralgia, rash healing, and treatment safety. Results Intent-to-treat analysis did not detect statistically significant differences for valacyclovir vs famciclovir on resolution of zoster-associated pain (hazard ratio, 1. 02; 95% confidence interval, 0.84-1.23; P =.84). Furthermore, no differences were evident between treatments on rash healing rates and on a range of analyses of postherpetic neuralgia. Safety profiles for valacyclovir and famciclovir were similar, with headache and nausea being the more common adverse events. Conclusions Valacyclovir treatment is comparable to famciclovir treatment in speeding the resolution of zoster-associated pain and postherpetic neuralgia. Current wholesale prices indicate that valacyclovir is the more cost-effective treatment for herpes zoster ($83.90 vs $140.70 per course).

Over the past decade, a large amount of attention has been directed toward the human papillomavirus (HPV) infection of the genital tract, whereas nongenital infections have been overlooked. These infections are clinically manifested as common warts. In essence, there is a broad spectrum of disease produced at nongenital sites by HPV. Different populations have different susceptibilities and consequences of HPV infection. The purpose of this paper is to review the clinical manifestations of nongenital HPV infection in the immunocompetent and the immunocompromised and those patients with epidermal dysplasia verruciformis. Consideration is given to the differential diagnosis and treatment.

A consensus process was undertaken to describe and evaluate current information and practice regarding the diagnosis, treatment, and evaluation of patients with external genital warts (EGWs) and their sex partners. This process developed a number of key statements that were based on strong evidence in the literature or reasonable suppositions and opinions of experts. Key statements included the following. In most cases, EGWs can be diagnosed clinically by visual inspection. No one treatment is ideal for all patients or all warts. Women with EGWs and female sex partners of men with EGWs are at increased risk for human papillomavirus-related cervical disease and, like all women, should be screened for cervical cancer. The diagnosis of EGWs in children requires a sexual abuse evaluation. Clinicians who treat EGWs have a responsibility to counsel patients and to provide information about the infectivity, diagnosis, treatment, and natural history of EGWs and general information about sexual health and other sexually transmitted diseases.

Genital warts are a common sexually transmitted disease caused by human papillomavirus. Imiquimod is a novel immune-response modifier capable of inducing a variety of cytokines, including interferon alfa, tumor necrosis factor-alpha, as well as interleukins 1, 6, and 8. In animal models imiquimod has demonstrated antiviral, antitumor, and adjuvant activity. In vitro, imiquimod has no antiviral or antitumor activity.Our purpose was to determine the safety and efficacy of topical imiquimod for the treatment of external genital warts.This prospective double-blind, placebo-controlled, parallel design clinical trial was performed in three outpatient centers, a public health clinic, a university-based clinic, and a private practice. One hundred eight patients with external genital warts (predominantly white men) were entered into the trial. Fifty-one patients were randomly selected to receive 5% imiquimod cream; 57 patients were randomly chosen to receive placebo cream. Study medication was applied three times weekly for up to 8 weeks. Patients whose warts cleared completely were observed for up to 10 weeks to determine recurrence rates.In the intent-to-treat analysis, the warts of 37% (19 of 51) of the imiquimod-treated patients and 0% (0 of 57) of the placebo group cleared completely (p0.001). In addition, many patients experienced a partial response. A reduction in baseline wart area of 80% or more was observed in 62% of imiquimod-treated patients (28 of 45) and 4% of the placebo group (2 of 50) (p0.001); a 50% reduction or more in wart area was noted in 76% of imiquimod-treated patients (34 of 45) and 8% of placebo recipients (4 of 50) (p0.001). Of imiquimod-treated patients whose warts cleared completely and who finished the 10-week follow-up period, 19% (3 of 16) experienced recurrences of warts. Imiquimod-treated patients experienced a significantly greater number of local inflammatory reactions than the placebo group. Symptoms and signs associated with the local inflammatory reactions included itching (54.2%), erythema (33.3%), burning (31.3%), irritation (16.7%), tenderness (12.5%), ulceration (10.4%), erosion (10.4%), and pain (8.3%). There were no differences in systemic reactions or laboratory abnormalities between treatment groups.Topical 5% imiquimod cream appears to have a significant therapeutic effect in the treatment of external genital warts.

Acyclovir treatment of acute herpes zoster speeds rash healing and decreases pain and ocular complications. The limited oral bioavailability of acyclovir necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, is rapidly and almost completely converted to acyclovir in vivo and gives three- to fivefold increases in acyclovir bioavailability. In a randomized, double-blind, multicenter study, the safety and efficacy of oral valaciclovir given at a dosage of 1,000 mg three times daily for 7 or 14 days and oral acyclovir given at a dosage of 800 mg five times daily for 7 days were compared in immunocompetent adults aged > or = 50 years with herpes zoster. Patients were evaluated for 6 months. The intent-to-treat analysis (1,141 patients) showed that valaciclovir for 7 or 14 days significantly accelerated the resolution of herpes zoster-associated pain (P = 0.001 and P = 0.03, respectively) compared with acyclovir; median pain durations were 38 and 44 days, respectively, versus 51 days for acyclovir. Treatment with valaciclovir also significantly reduced the duration of postherpetic neuralgia and decreased the proportion of patients with pain persisting for 6 months (19.3 versus 25.7%). However, there were no differences between treatments in pain intensity or quality-of-life measures. Cutaneous manifestations resolved at similar rates in all groups. Adverse events were similar in nature and prevalence among groups, and no clinically important changes occurred in hematology or clinical chemistry parameters. Thus, in the management of immunocompetent patients > or = 50 years of age with localized herpes zoster, valaciclovir given at 1,000 mg three times daily for 7 days accelerates the resolution of pain and offers simpler dosing, while it maintains the favorable safety profile of acyclovir.

Human papillomavirus infection represents the most common mucocutaneous viral infection, and 3% to 5% of all patients have clinically evident warts. Human papillomavirus infections of the genital tract are one of the most common sexually transmitted viral infections in the United States. Data from STD clinics and private physicians' offices reveal that genital warts, one manifestation of genital HPV infection, have been diagnosed more frequently in recent years. With the use of a variety of diagnostic techniques, asymptomatic HPV infection has been identified in men and women and is probably much more common than is clinically apparent infection.

Onychomycosis is a fungal infection of the fingernails and toenails that results in thickening, discoloration, splitting of the nails and lifting of the nail from the nail bed. The disease is caused by dermatophytes and has a high incidence within the general population, especially among older individuals. Present treatment options include both oral and topical drugs, with oral therapies giving better outcomes; however, neither of these treatment options provides high cure rates that are durable. The difficulty in treating onychomycosis results from the deep-seated nature of the infection within the nail unit (nail plate, nail bed and surrounding tissue) and the inability of drugs to effectively reach all sites. Ongoing drug development activities have focused on novel delivery technologies to facilitate penetration of existing antifungal drugs through the nail plate and on the discovery of inherently penetrable antifungals. AN-2690 represents an oxaborole antifungal that is designed to penetrate the nail plate and is showing promising results in clinical trials.

To determine whether men are able to self-diagnose external genital warts (EGWs), we studied data from 1115 men with and without human immunodeficiency virus infection. Men were largely unable to accurately assess the presence of EGWs. Self-reporting of EGWs was not a sensitive tool; only 38% of men who had EGWs diagnosed by a trained examiner who used bright light and visual inspection also reported having them. When we controlled for other covariates in a multivariate model, men who had EGWs diagnosed by an examiner were 14 times less likely to show concordance between examiner findings and self-report than were men who did not have EGWs diagnosed by an examiner (odds ratio, 0.07; 95% confidence interval, 0.06-0.09). Self-diagnosis and self-assessment may not accurately reflect the presence of EGWs, and self-diagnosis should not be used in place of an examiner's findings for epidemiologic studies that seek to determine the cause of disease.

Most genital human papillomavirus (HPV) infections are benign. Subclinical genital infections with HPV are extremely common. Genital HPV infections cause a spectrum of diseases, ranging from asymptomatic infection to invasive cervical cancer. The HPV types are divided into low- and high-risk viruses, based on their association with cervical cancer. When the low-risk HPV infections are clinically expressed, they produce external genital warts. Once clinically apparent, they may persist, spread, grow, spontaneously regress, and/or recur. The high-risk HPV types cause abnormal Pap smears, low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), atypical squamous cells of uncertain significance (ASCUS), and atypical glandular cells of uncertain significance (AGUS). When the high-risk HPV types are clinically recognized on the external genital area, they cause formation of papular lesions. A useful strategy for HPV control is immunotherapy. Adoptive cellular transfers involve collection of the cells involved in host defenses from patients with cervical cancer; then growing these cells; activating them ex vivo by cytokines, such as the recombinant IL-2; and transferring them back to the cancer patient as therapy.

Background: Basal cell carcinoma (BCC) responds to interferon therapy. Imiquimod is a cytokine and interferon inducer. Objective: This randomized, double-blind pilot trial evaluated the safety and efficacy of imiquimod 5% cream versus vehicle in the treatment of BCC. Methods: In this population of 35 patients with BCC, 24 received imiquimod 5% cream and 11 received vehicle cream in 1 of 5 dosing regimens for up to 16 weeks. Six weeks after treatment, an excisional biopsy of the target site was performed. Results: BCC cleared (on the basis of histologic examination) in all 15 patients (100%) dosed twice daily, once daily, and 3 times weekly; in 3 of 5 (60%) patients dosed twice weekly; 2 of 4 (50%) dosed once weekly; and in 1 of 11 (9%) treated with vehicle. Adverse events were predominantly local reactions at the target tumor site, with the incidence and severity of local skin reactions declining in groups dosed less frequently. Conclusion: Imiquimod 5% cream shows clinical efficacy in the treatment of BCC. (J Am Acad Dermatol 1999;41:1002-7.)

Education and counseling constitute a substantial portion of management of patients with genital herpes. Innovative methods for education about genital herpes are needed.To test the ability of an interactive, computer-based program to educate patients about genital herpes.Persons seeking care at five urban offices were asked to participate. A knowledge test about genital herpes was administered before and after participation. Participants' satisfaction was assessed with a questionnaire.Four hundred thirty-five participants enrolled, and 428 completed the herpes knowledge test. Of six questions evaluated, a statistically significant increase in the proportion of correct answers was noted on five of six questions. Fifty-one percent of participants answered all the questions correctly after the program, compared with 39% before the program. Satisfaction with the program was very high.Innovative, computer-based programs can provide education and assist in the management of chronic sexually transmitted infections.

Genital warts are manifestations of a common viral sexually transmitted disease (STD) that are often diagnosed and treated with a variety of clinical specialties. Unlike for other STDs, there is a general lack of a well-established treatment algorithm for the management of external genital warts. This, coupled with a wide variety of treatments and clinical settings, makes the development of a simple algorithm virtually impossible. In this review what is known and not known about current treatments and case management will be discussed.

A multi-center, randomized, double-blind, placebo-controlled trial was performed to evaluate the effectiveness of butenafine, a fungicidal benzylamine derivative, in the once daily treatment of interdigital tinea pedis. One hundred and fifty patients with interdigital tinea pedis characterized by a minimum erythema score of 2 and a minimum score of 2 for either pruritus or scaling (on a scale of 0–3, where ‘2’ defines moderate severity) were initially enrolled, pending confirmation by mycologic culture and KOH testing. Patients were excluded if the evaluation of tinea pedis might have been impaired by concomitant conditions, if they were hypersensitive to allylamines or ingredients of the study medications, or if they had clinically significant abnormal laboratory values. Women of childbearing potential were also excluded if they were pregnant, lactating, or not using adequate contraceptive measures. The patients were randomized and given study formulations in coded tubes containing either butenafine hydrochloride cream 1% (butenafine) or the vehicle. They were instructed to apply the formulation to all tinea pedis lesions one daily, for 4 weeks. They were evaluated after 1, 2, and 4 weeks of treatment, and again 4 weeks post-treatment, using the following measures: (i) mycologic cure: negative fungal culture and KOH test; (ii) effective treatment: mycologic cure and investigator global assessment of 80% or more improvement in signs and symptoms; (iii) investigator global assessment of clinical response: cleared (100% improvement in signs and symptoms), excellent (80–99% improvement), good (50–79% improvement), fair (25–49% improvement), poor (less than 25% improvement), unchanged, or worse, (iv) patient’s assessment of change since baseline: 5=greatly improved, 4=somewhat improved, 3=the same, 2=somewhat worse, and 1=much worse. Mycologic cure and effective treatment were each analyzed using the Cochran–Mantel–Haenszel (CMH) test of response by treatment partialled on investigator. Patient perceptions and investigator evaluations of global response were analyzed as ordered categorical data using the CMH mean score test with uniform scores.

Genital human papillomavirus infection is one of the most common sexually transmitted diseases. Imiquimod is a new agent, an immune-response modifier, that has been demonstrated to have potent in vivo antiviral and antitumor effects in animal models. The present prospective, multicenter, double-blind, randomized, vehicle-controlled trial evaluated the efficacy and safety of daily patient-applied imiquimod for up to 16 weeks for the treatment of external genital warts. Wart recurrence was investigated during a 12-week treatment-free follow-up period. In the intent-to-treat analysis, baseline warts cleared from 49 of 94 (52%) patients treated with 5% imiquimod cream, 13 of 90 (14%) patients treated with 1% imiquimod cream, and 3 of 95 (4%) vehicle-treated patients; the differences between the groups treated with vehicle and imiquimod were significant ( P < 0.0001). For subjects who completed the follow-up period, recurrence rates after a complete response were 19% (9 of 48 patients) in the 5% imiquimod cream group, 17% (2 of 12) in the 1% imiquimod cream group, and 0% (0 of 3) in the vehicle-treated group. There were no systemic reactions, although local skin reactions (generally of mild or moderate severity) were common, particularly in the 5% imiquimod cream group. Local reactions caused two patients to discontinue treatment. The most frequently reported local skin reactions were erythema, excoriation or flaking, and erosion. Patient-applied 5% imiquimod cream is effective for the treatment of external genital warts and has a favorable safety profile.

The relationship between human papilloma virus (HPV) and cervical cancer is in the process of being defined. This potential opportunity to understand a human oncogenic virus has drawn significant attention to HPV. While cervical cancer is a potentially fatal outcome of HPV infection, genital warts are the most common manifestation of genital HPV infection. In addition to knowledge of etiology, natural history, and therapeutic options, patients and providers need to consider emotional impact to successfully manage the care of patients with this common infection. This article summarizes current knowledge of recent advances of HPV infection of the vulva.

This randomized, placebo-controlled trial was conducted to determine the efficacy of daily antiviral therapy (valacyclovir) in preventing the transmission of herpes simplex virus type 2 (HSV-2) in monogamous couples with 1 infected partner. Heterosexual couples over 18 years of age, with 1 noninfected partner and 1 HSV-2-seropositive partner who had fewer than 10 outbreaks of genital herpes per year, were identified and recruited from participating medical centers. They were enrolled for an 8-month study period during which the infected partner took 500 mg valacyclovir or placebo once daily. Susceptible partners had monthly clinical examinations for the presence of HSV-2. Infected partners were seen during each outbreak of genital herpes and treated with 500 mg valacyclovir twice daily for 5 days. Couples were given a free supply of condoms and instructed to use them. In addition, 89 infected participants were recruited to participate in a substudy of mucosal shedding. Everyday for 2 months, they swabbed their genital area and placed the swabs in polylmerase chain reaction (PCR) buffer, which was delivered to the clinic with the next monthly visit. One thousand four hundred eighty-four couples, including 488 women and 996 men who were not HSV-2-seropositive, met the requirements for inclusion in the analysis. There were 743 couples randomized to the valacyclovir group and 741 in the placebo group. Seventy-one susceptible partners developed symptoms suggestive of HSV-2 infection. Clinical and laboratory evidence confirmed the diagnosis in 20, including 4 from the valacyclovir group (4 of 743; 1.9%) and 16 (16 of 741; 3.6%) in the placebo group (hazard ratio, 0.52; 95% confidence interval, 0.27-0.99; P = 0.01). Among those with symptoms, 3 were determined to have become infected before the development of symptoms, and 48 had no evidence of infection on clinical examination. Of the susceptible subjects who reported no symptoms, 18 were found to have laboratory evidence of HSV-2 infection. Overall, there were 41 subjects who acquired HSV-2 during the course of the study, including 14 with partners taking valacyclovir and 27 who were partners of subjects receiving placebo. Among the 20 susceptible partners who had symptoms of genital herpes, the time to development of symptoms was found to be significantly longer in those whose partners were taking valacyclovir compared with the partners of placebo recipients. Female partners of those taking placebos were more likely to acquire HSV-2 infection than male partners (7.4% vs. 1.9%). Recurrence of symptoms was twice as common among the placebo recipients than among those taking valacyclovir (77.3% vs. 38.8%; P

The objective of this study was to evaluate the patient acceptability of a 10% sodium sulfacetamide and 5% sulfur cleanser in patients with mild-to-severe rosacea. This was a single-center, open-label, 4-week study involving 34 enrolled patients (31 of whom completed all visits). All patients were prescribed (metronidazole gel 0.75%) to be used twice daily after washing with the sulfacetamide/sulfur cleanser. The investigator’s assessment of product tolerability involved a 4-point scale to evaluate dryness, scaling, pruritis, and stinging/burning. Patients were asked to assess various skin sensations after product use (eg, “feels soft/smooth‘) on a 6-point scale. In addition, the investigators performed an inflammatory lesion count and assessed erythema severity and global rosacea severity. Investigator assessment of product tolerability showed that the average score for each potential adverse effect decreased over the course of the study. Patient evaluation demonstrated that the average score for each subjective assessment decreased from or remained similar to baseline at the week 4 visit. There was a numerical trend toward improvement in disease-state evaluations (lesion counts, erythema severity score, and global rosacea severity score) over the course of the study.

Since the early 1940s podophyllum resin has been used for the treatment of genital warts [1]. Physician’s use, acceptance, and perceived efficacy of this resin varies greatly. This is in part a reflection of the heterogeneity of podophyllin preparations as well as a lack of a well-defined treatment regimen for the resin. Since Kaplan’s original report nearly 50 years ago little has changed in how this resin is used in the treatment of genital warts. The effect of resin source, concentration frequency of application, and vehicle on safety and efficacy have not been studied.

Objective: Education of patients with genital herpes about their disease is time consuming. To evaluate the effectiveness of an educational computer program, we developed a multimedia interactive presentation to teach patients about genital herpes. Such programs can supplement clinician visits for patients with genital herpes, or those at risk for HSV acquisition. Methods: Patients seeking care for genital herpes, or those at risk for HSV acquisition, were asked to participate in the program during routine clinic visits at 5 physician’s offices nationwide. A self-administered 7 item herpes knowledge questionnaire was given before and after participation. An additional questionnaire evaluating the satisfaction with the program was also self-administered at completion. Results: 428 patients were enrolled and completed the pre- and post-knowledge questionnaire and 332 patients completed the satisfaction survey. On the pre-test, 20.1% of patients answered all questions correctly, 65.4% answered correctly 4 to 6 questions, and 14.5% 3 or less. On the post-test, 32.9% of patients answered all questions correctly, 61.5% answered correctly 4 to 6 questions, and 5.6% 3 or less (P < .001 for pre- and post-test comparison). A positive change in knowledge between pre- and post-test was seen on 6 of 7 items (P < .001 for all 6). The overall satisfaction with the program was high: the mean rating was 6.2 on a scale 1 (poor) to 7 (excellent). Conclusion: Computer-based education programs about genital herpes may provide a useful adjunct to teaching in physician offices and result in knowledge gain about the disease, at least short-term. Such programs may assist in management of chronic sexually transmitted infections.

Background: Valaciclovir, the 1-valyl ester of acyclovir, has provided a peroral acyclovir bioavailability 3 to 5 times that of acyclovir itself and is rapidly and completely converted to acyclovir by the liver. Accordingly, valaciclovir has the same antiviral activity as acyclovir, but the potential for enhanced clinical activity and/or less frequent administration because of its superior pharmacokinetics. Methods: We conducted a double-blind, placebo-controlled, patient-initiated clinical trial of peroral valaciclovir, 500 or 1000 mg, or matching placebo tablets twice daily for 5 days for the acute treatment of 1 episode of recurrent herpes genitalis among 987 otherwise healthy volunteers. Results: Both doses of valaciclovir were equally effective. Patients receiving the lower dose of valaciclovir experienced a median episode length of 4.0 days compared with 5.9 days for those receiving placebo treatment (hazard ratio, 1.9; 95% confidence interval [CI], 1.6-2.3). Valaciclovir therapy increased the proportion of patients in whom the development of vesicular and ulcer-ative lesions was prevented in comparison with placebo treatment: 31% vs 21% (relative risk, 1.5; 95% CI, 1.1-1.9). Valaciclovir therapy accelerated the resolution of pain (hazard ratio, 1.8; 95% CI, 1.5-2.1) and the time to cessation of viral shedding (hazard ratio, 2.9; 95% CI, 2.1-3.9). Adverse reactions among the valaciclovir groups were comparable with those of the placebo group. Conclusions: Valaciclovir therapy provided a clinically significant benefit to patients that included shortening of the duration of lesions, the duration of pain or discomfort, and the duration of virus shedding. In addition, this study, to our knowledge, provides the first convincing demonstration that antiviral therapy can prevent lesion development. These results should prompt a reconsideration of the role that episodic treatment plays in the management of recurrent herpes genitalis. Arch Intern Med. 1996;156:1729-1735

Until a modern equivalent of spunk water is available, what are reasonable expectations of wart therapy? What is the oncogenic potential of human papillomavirus (HPV) and what should we tell patients to adequately inform them without terrorizing them? Despite a great increase in the number of publications and an ever growing body of information about HPV infection, HPV molecular biology, and virology, there remains a paucity of clinically applicable knowledge about this common infection. This brief overview summarizes the current knowledge relevant to common clinical issues in an attempt to bridge the gap between information and knowledge. It is clear that HPV produces a latent infection. Human papillomavirus(es) is a group (at least 60 types) of epithelialtrophic viruses that result in latent infection and a spectrum of clinical disease. 1,2 The latent nature of the infection is demonstrated by at least four observations. First, subjects with no clinical history of HPV infection have antibodies to HPV. 3 Second, HPV DNA is present in normal mucosa from patients with laryngeal papillomatosis." Third, HPV DNA is present in normal tissue obtained 0.5 to 1.0 cm beyond surgical margins in women with vulvar warts. 5

The health care personnel (HCP) of an institution for the mentally handicapped were serially tested for the presence of hepatitis B surface antigen (HBSAg) and antibody over a period of 1.5 years. HBSAg was present in 1.8% and anti-HBS in 20.8% of HCP. The prevalence of seropositive HCP appeared to be related to the age and the prevalence of seropositive residents cared for by the HCP. The occurrence of seropositivity was higher in the HCP who cared for children under 15 years of age, who demonstrated a high prevalence of HBSAg or anti-HBS. Although the prevalence of HBSAg-positive subjects was 4- to 8-fold lower in HCP than in residents, the degree of seroconversion in susceptible seronegative HCP and residents was strikingly similar. These observations suggest that HCP working in a closed institutional setting are at considerable risk of contacting hepatitis B infection.

Es war fruher gezeigt, das Kephalin einen verstarkenden Einflus auf die Wirkung einiger Gifte ausubt. Da Ultrafiltrate von Kephalin auch wirksam waren, so war die Moglichkeit in Betracht zu ziehen, das die Verstarkungswirkung durch Zersetzungsprodukte des Kephalins zustande kam. Deshalb wurden Zersetzungsprodukte von Kephalin und einige verwandte Substanzen untersucht. Dies fuhrte zur Untersuchung der Natriumsalze von vier Fettsauren, namlich: Olsaure, Stearinsaure, Linolsaure und Linolensaure. Natriumoleat erwies sich als sehr wirksam. Verdunnungen von 1 auf 60 Milliarden hatten noch eine deutliche Verstarkungswirkung auf Pilokarpin. Stearinsaure war auch wirksam, aber nicht annahernd so stark wie Olsaure. Linolsaure war auch wirksam, aber schwacher wie Stearinsaure, wahrend Linolensaure kaum eine Wirkung hatte.

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ConclusionThiouracil and thiourea in addition to preventing the synthesis of the thyroid hormone has some effect on thyroid per se when fed to white mice.

† A 44-year-old man with Hodgkin's disease developed fever and erythematous macules and plaques associated with doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy. Biopsy results demonstrated a neutrophilic infiltrate around sweat glands and degeneration of eccrine glands. These findings are characteristic of neutrophilic eccrine hidradenitis, which, to our knowledge, has previously been reported only in patients with acute myelogenous leukemia who were receiving cytarabine chemotherapy. Neutrophilic eccrine hidradenitis may represent a reaction pattern to chemotherapeutic agents and may not be specific for a particular disease or drug. (Arch Dermatol1986;122:809-811)

In Reply.— We appreciate the comments of Dr Fiumara regarding our recently published case report. The article describes a case of clinical relapse of secondary syphilis after treatment with the CDC's recommended regimen. 1,2 It was not our intention to indicate that the CDC guidelines are "inadequate" but rather to demonstrate that failures do occur and to stress the importance of careful follow-up. In fact, we suggest that the present regimen should continue to be employed until appropriately controlled studies demonstrate superiority of an alternative approach. We are familiar with Dr Fiumara's extensive experience using a total of 4.8 million units of penicillin G benzathine intramuscularly to treat primary and secondary syphilis. We take issue, however, with his suggestion that a study comparing 2.4 and 4.8 million units of intramuscular penicillin G benzathine has already been performed. In the study to which he refers, 3 a treatment arm employing 4.8