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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.

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 (

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.

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.

Human papillomaviruses (HPVs) are associated with a spectrum of different diseases in humans, including common warts and genital warts. Of more serious concern is the connection between certain HPV types and some malignancies, particularly cervical and anal cancer. DNA from HPV-16 and HPV-18, two types frequently found in cervical cancer tissue, can immortalize cells in laboratory cultures, unlike DNA from HPV types associated with benign genital lesions. Although it is unclear how high-risk HPV types cause cancer, studies indicate that malignant transformation involves the viral E6 and E7 gene products, which may exert their effect by interfering with the cellular proteins that regulate cell growth. The vast majority of those infected do not develop malignancies, indicating that HPV infection alone is not enough to cause cancer. Cofactors such as cigarette smoking, may be required before neoplasia can occur. The potential seriousness of HPV infections is suggested by the observations that the number of genital HPV infections diagnosed is increasing and that cervical cancer is the second leading cause of cancer deaths in women throughout the world.

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.

Over the past several years, there has been an increase in knowledge pertaining to the diagnosis and management strategies for the herpes family (Types 1-8), the pox viruses, mumps, measles, rubella, and parvovirus B19 as well as the viral etiologies of hepatitis. Various antiviral treatments, such as nucleoside analogs and interferon therapy, have been available to reduce the signs and symptoms of these common viral infections. This article summarizes the preferred treatment strategies to be employed for each of the viruses for reducing severity, duration, recurrences (notably in the herpes family), transmission rates, as well as preventive alternatives. The majority of the therapeutic options attenuate the course of disease. Treatment decisions are driven by knowledge of the natural history and often are tailored to incorporate clinical circumstances for individual patients. Promotion of community awareness and the development of vaccines should be emphasized in the battle against these common viruses, particularly the herpes simplex viruses, the pox viruses, and hepatitis B.

The herpesviruses continue to produce considerable morbidity in man. Once infected with herpes simplex (HSV), the virus remains dormant within the nervous system and may reactivate if provoked by stress, trauma and/or other factors. To date, there is no cure, but antiviral medication can reduce duration and severity of symptoms and prophylaxis can suppress recurrent episodes of disease. The second-generation guanosine nucleosides, acyclovir and penciclovir, are effective inhibitors with low toxicity; both, however, have relatively low oral bioavailability. Subsequently, the orally bioavailable prodrugs valaciclovir and famciclovir have been introduced. These compounds offer high oral bioavailabilty and deliver acyclovir and penciclovir, respectively, to the target cells by means of more convenient dosing schedules. This short review points to recent experience with famciclovir in the management of HSV and varicella-zoster virus.

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.

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.

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.

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.

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 presence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), hepatitis B e antigen (HBeAg) and antibody (anti-HBe), the nature of T-cell function, and specific cell-mediated immunity to HBsAg were determined and evaluated serially in groups of subjects with chronic HBsAg carrier states and in seronegative controls. The techniques of in vitro lymphocyte transformation, spontaneous rosette formation, radioimmunoassay, reverse passive hemagglutination, passive hemagglutination, rheophoresis, and liver function tests were employed for these studies. For the lymphocyte transformation assay, multiple concentrations of phytohemagglutinin and purified HBsAg were used as stimulants. Cell-mediated immunity to HBsAg was detectable in 50% of the chronic HBsAg carriers (responders) at one or more concentrations of HBsAg. The remaining carriers (nonresponders) and controls failed to manifest HBsAg-specific lymphocyte transformation activity. The profile of the responders was characterized by elevated serum glutamic pyruvic transaminase levels, the presence of anti-HBe, high HBsAg titers, and the conspicuous absence of HBeAg in the serum. The nonresponders were characterized by normal serum glutamic pyruvic transaminase levels, the presence of HBeAg and anti-HBe, and lower HBsAg titers. These observations demonstrate the presence of specific cell-mediated immunity to HBsAg in chronic HBsAg carriers who manifest biochemical evidence of liver disease.

Sera from 99 chronic hepatitis B surface antigen carriers, 12 individuals with acute type B hepatitis, 26 hepatitis B surface antibody-seropositive subjects, and 50 hepatitis B surface antigen, hepatitis B surface antibody-seronegative subjects were evaluated for the presence of serum imunoconglutinis (IKs). The mean serum IK titers of hepatitis B surface antibody-seropositive and hepatitis B virus-seronegative subjects wre 5.3 and 4.9, respectively. The IK titers of subjects with acute and chronic hepatitis B virus infections were 215.4 and 19.1, respectively. These groups also manifested IK titers greater than or equal to > 16 significantly (P < 0.005) more often than controls did. Among chronic hepatitis B surface antigen carriers, high IK titers were associated with low levels of hepatitis B surface antigen. IK titers of individuals chronically infected with hepatitis B virus and having the rheumatoid factor were similar to those of individuals without the rheumatoid factor. Elevated IK titers represent a physiological autoimmune response and may indicate the presence of immune complexes in acute and chronic hepatitis B virus infection.

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.

Employing the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transformation assay, the antibody and cell-mediated immunity to cytomegalovirus (CMV) were studied in the serum, peripheral blood lymphocytes, tonsillar lymphocytes, and cord blood lymphocytes. The study population consisted of 32 children undergoing tonsillectomy and adenoidectomy. In the lymphocyte transformation assay, three strains of CMV (AD-169, ADH-1-41, and Davis), herpes simplex type 1, and phytohemagglutinin were employed as antigens. Sixty-five percent of the subjects were found to have CMV-specific antibody activity. The lymphocyte transformation response to phytohemagglutinin was similar in all subjects. No CMV-specific lymphocyte transformation activity was detected in cultures of cord blood lymphocytes. Significant cell-mediated immunity was observed in the tonsillar lymphocytes of 30% (3/10) of the seronegative individuals and in the peripheral blood lymphocytes obtained from one such subject. Over 75% (16/21) of the seropositive subjects demonstrated cell-mediated immunity against one or more strains of CMV in the peripheral blood lymphocytes and tonsillar lymphocytes. In the lymphocyte transformation assay, no cross-reactivity was apparent between CMV and herpes simplex type 1. These studies demonstrate the presence of strain-specific systemic and mucosal cell-mediated immune response to CMV in humans. The frequency and distribution of lymphocyte transformation responses to the three CMV strains suggest antigenic heterogeneity of CMV.

The techniques of hemagglutination inhibition and in vitro lymphocyte transformation and the assay of migration inhibitory factor were used for study of the development of rubella antibody activity in serum and tonsillar tissue washings and of the appearance of rubella-specific, cell-mediated immunity in circulating and tonsillar lymphocytes in groups of children who underwent tonsillectomy at various intervals after natural rubella infection, subcutaneous immunization with HPV-77 DE/5 vaccine, or intranasal inoculation with RA27/3 live, attenuated rubella virus vaccine. Antibody response in serum and tonsillar tissue washings was detected regularly after natural infection or immunization. Development of specific cellmediated immunity in circulating lymphocytes was regularly observed after natural infection and frequently after immunization. Natural infection or intranasal immunization with rubella vaccine resulted in the appearance of cell-mediated immunity in the tonsillar lymphoid tissue, and the response was detectable up to several years after natural infection in several cases. It is significant, however, that the level of cell-mediated immunity in tonsils was conspicuously low after subcutaneous immunization. These data suggest the induction of local cell-mediated immunity in tonsillar lymphoid tissue after local mucosal application of rubella virus. It has been shown that nasopharyngeal antibody plays an important role in the protection against reinfection with rubella [1] and other viruses [2]. However, no information is available regarding the development and role of mucosal cellmediated immune responses and their participation in the mucosal immune function. We initiated the present studies to examine the appearance of the cell-mediated immune response in tonsillar lymphocytes to rubella virus after natural infection or immunization with live at

The in vitro correlates of cell-mediated immunity to liver tissue antigens and hepatitis B surface antigen (HBsAg) were studied in groups of subjects with acute and chronic hepatitis B virus (HBV) infection and in a population of HBV-seronegative controls. The technique of in vitro lymphocyte transformation (LTF) was employed in these studies. No LTF response to liver-specific antigen and HBsAg was observed in the control population. LTF activity in response to HBsAg was present in 11 of the 14 subjects with acute type B viral hepatitis during the early phase of the disease, and eight of these subjects also had LTF reactivity to liver antigen. During the convalescent phase the LTF reactivity to these antigens usually disappeared. More than 70% of patients with chronic carriage of HBsAg who had elevated levels of liver enzymes showed LTF responses to HBsAg, and a significant number of these subjects also exhibited LTF response to liver-specific antigen. On the other hand, chronic HBsAg carriers who persistently showed normal liver enzyme values (asymptomatic carriers) failed to show significant responses to liver antigen or HBsAg. It is suggested that the persistence of cellular reactivity to liver antigens may lead to the establishment of chronic liver disease.

† 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

The appearance of rubella specific cell-mediated immunity (CMI) in tonsillar and adenoidal lymphoid tissue and in circulating lymphocytes, and antibody activity in serum and nasopharyngeal secretions was studied in groups of children who underwent tonsillectomy and adenoidectomy (T&A) at varying intervals after natural rubella infection, subcutaneous immunization with HPV-77 or intranasal inoculation of RA27 rubella vaccine. The techniques of hemagglutination-inhibition, autoradiography, in-vitro lymphocyte transformation and assay of migratory inhibitory factor using rubella virus as the antigen were employed to determine antibody and CMI in serum and secretory sites. Serum antibody response was elicited regularly after natural or induced infection. Nasopharyngeal antibody response was observed only after natural infection or RA27 immunization. Development of specific CMI in circulating lymphocytes was regularly observed after natural infection and frequently after immunization. Natural infection or intranasal immunization with rubella vaccine resulted in the appearance of CMI in the tonsillar and adenoidal lymphoid tissue, and the response persisted for 3-4 months. Significantly however, CMI activity in tonsils and adenoids was conspicuously absent after subcutaneous immunization. These data suggest the existence of locally induced cellular immune components in the mechanism of mucosal defense against viral infections.