Brenda L. Bartlett

Epidermodysplasia verruciformis and human papilloma virus.

Purpose of reviewDespite its rarity, epidermodysplasia verruciformis was addressed in depth in recent literature. Patients are afflicted by persistent human papillomavirus infections and develop cutaneous malignancies more frequently and younger than in the general population. The disease is therefore considered a model for a viral role in cutaneous oncogenesis, although implication is controversial. We focus on recent findings in genetics, highlight multiple viewpoints regarding the role of epidermodysplasia verruciformis-human papillomavirus in nonmelanoma skin cancer and other diseases, and discuss treatment strategies. Recent findingsSusceptibility loci for epidermodysplasia verruciformis were mapped and encoded protein functions are becoming better understood, but a unified genetic theory for epidermodysplasia verruciformis is lacking. Epidermodysplasia verruciformis-human papillomavirus, originally thought present only in epidermodysplasia verruciformis, is now considered ubiquitous, its role still being elucidated. Numerous therapies for epidermodysplasia verruciformis lesions were proposed, although there is no consensual first-line treatment strategy. SummaryDiscoveries of novel mutations and further study of epidermodysplasia verruciformis-human papillomavirus in lesional and nonlesional skin of epidermodysplasia verruciformis patients and the general population may generate a cohesive theory regarding a viral role in cutaneous oncogenesis. Future understanding of the disease may yield an optimal approach to treating epidermodysplasia verruciformis patients.

The Expanding Spectrum of Eschar-Associated Rickettsioses in the United States

BACKGROUND Until recently, Rickettsia rickettsii was the only substantiated cause of tick-borne spotted fever group (SFG) rickettsiosis in humans in the United States. Rickettsia parkeri, originally thought to be nonpathogenic in humans, was recently proved to be another cause of tick-borne SFG rickettsiosis. OBSERVATIONS We report 3 cases of SFG rickettsiosis and discuss the epidemiology, clinical presentation, histopathologic features, and laboratory findings that support confirmed or probable diagnoses of R parkeri infection and describe the expanding list of eschar-associated SFG rickettsioses recognized in US patients. CONCLUSIONS The SFG rickettsioses share many clinical manifestations and extensive antigenic cross-reactivity that may hamper specific confirmation of the causative agent.

Mucocutaneous Manifestations of Epstein-Barr Virus Infection

This review focuses on Epstein-Barr virus (EBV) infection, diagnosis, and current treatment, with emphasis on EBV-associated mucocutaneous manifestations in primary infections, acute EBV-associated syndromes, chronic infections, lymphoproliferative disorders, and lymphomas. In primary infection, EBV infects B cells and can cause mucocutaneous manifestations in infectious mononucleosis or acute EBV-associated syndromes such as Gianotti-Crosti syndrome and hemophagocytic syndrome. EBV then persists in the majority of humans generally without causing disease. In some cases, however, latent EBV infection may result in diseases such as hydroa vacciniforme, hypersensitivity to mosquito bites, and lymphoproliferative disorders such as plasmablas- tic lymphoma, oral hairy leukoplakia, and post-transplant lymphoproliferative disorders, particularly in immunocompromised patients. Latent EBV infection has also been implicated in a variety of malignant conditions such as Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and Kikuchi histocytic necrotizing lymphadenitis. Since the immune system is critical in preventing the progression of EBV disease, the immunologic status of the patient plays a crucial role in the subsequent development of pathologies.

Famciclovir treatment options for patients with frequent outbreaks of recurrent genital herpes : The RELIEF trial

BACKGROUND Recurrent genital HSV outbreaks are common among those suffering from the disease. Antiviral medications taken as suppressive therapy can reduce the frequency of these recurrences and reduce viral shedding occurring in between recurrences. OBJECTIVES To investigate the efficacy and safety of oral famciclovir as episodic (125 mg twice daily for 5 days) and suppressive (250 mg twice daily) treatment of recurrent genital herpes (RGH). STUDY DESIGN This was a randomized, multicenter, 6-month, open-label study. Efficacy variables were time to first recurrence of RGH symptoms, and change in total score of the Recurrent Genital Herpes Quality of Life (RGHQoL) questionnaire. Subject satisfaction questions were summarized. RESULTS 384 subjects were randomized. There was a highly statistically significant difference between treatments in time to first recurrence of symptoms in favor of suppressive treatment (p<0.0001). There was no significant difference between treatments in total score of the RGHQoL or in subject satisfaction with treatment. CONCLUSIONS This study demonstrated that, compared to episodic treatment, suppressive treatment with oral famciclovir may extend the time to symptomatic outbreaks in patients with frequent recurrences of genital herpes.

Single-day treatment for orolabial and genital herpes: a brief review of pathogenesis and pharmacology

Herpes simplex virus (HSV) infection is a highly prevalent condition responsible for significant morbidity and occasional mortality each year. Approximately half of all patients infected by HSV will experience at least one recurrence in their lifetime. For these recurrences, traditional therapy has included both suppressive and episodic treatment with nucleoside analogs. In regards to episodic treatment, 2- to 5-day oral regimens are best studied and most commonly reported. As with any medical condition having a well-understood mechanism of action and targeted treatment, therapeutic intervention is only as effective as allowed by patient compliance. Based on these concerns, recent studies have focused on shorter, less complicated, and more affordable options. This review delineates the evidence for single-day treatments of orolabial and genital herpes. Randomized, double-blind studies of both valacyclovir and famciclovir as single-day episodic therapy for HSV have been reported in the literature. Although no head-to-head studies between the drugs have been performed, both regimens produced significant improvement in healing time and symptom resolution over placebo. Single-day therapy for HSV infection is appealing for multiple reasons. First, it simplifies the regimen, increasing likelihood of patient compliance. Additionally, it allows complete delivery of the medication at the onset of symptoms, when viral replication is highest and intervention has greatest effect. Lastly, the reduced number of pills necessary for single versus multiple day therapy decreases the overall cost of treatment per episode, an important factor in modern-day healthcare.

A rare case of disseminated shingles in an immunocompetent patient following a 7-day treatment with oral valacyclovir

Varicella-zoster virus (VZV) is the causative agent of both chickenpox and herpes zoster (shingles). More than 90% of the adult population in theUnited States is seropositive for VZV. VZV remains latent in the dorsal root and cranial nerve ganglia after chickenpox and reactivates to give rise to herpes zoster.1 Herpes zoster affects over 1 million Americans each year, and 60% of cases occur in individuals over the age of 50.2 Dissemination of herpes zoster, although extremely rare in immunocompetent patients, may be as high as 10–40% in immunocompromised hosts.3 We report a case of disseminated herpes zoster in a young, immunocompetent man following a 7-day treatment with valacyclovir.

Safety and efficacy of vaccines

For the past two centuries, vaccines have provided a safe and effective means of preventing a number of infectious diseases. Although the safety of some vaccines has been questioned in recent years, the currently available vaccines are more than a millionfold safer than the diseases they are designed to prevent. Vaccines, however, should always be used in conjunction with other public health interventions. One important intervention is education because the general public can be led to believe that vaccines are unsafe and not needed by misinformation readily available electronically and in print. Not only are some vaccines available via injection but other vaccines are also given orally or intranasally. New vaccines are being studied for topical and intravaginal use. In addition, new systems are being developed for more efficient production of vaccines, especially for influenza. Vaccines are currently available for only a limited number of viral and bacterial diseases. In the future, it is anticipated that safe and effective vaccines will be developed against a number of other viral and bacterial infections as well as fungal and protozoan diseases.

Vaccines under study: non-HIV vaccines.

The development of effective vaccines has been an amazing public health achievement and has resulted in countless lives being saved. Dermatologic therapy has recently been greatly advanced by the licensure of an effective human papillomavirus vaccine and herpes zoster vaccine. Despite these successes, many infectious diseases do not currently have a preventive vaccine. We review potential vaccines against selected infectious agents, including viruses, bacteria, fungi, and protozoa that have cutaneous and mucocutaneous manifestations. The road to licensure of a new vaccine begins with exhaustive preclinical and clinical studies, and many of these will fail before a successful vaccine candidate is approved. This article focuses on vaccines that have yet to be approved for licensure.

Vaccines for the prevention of infectious diseases with mucocutaneous manifestations.

For over 200 years, vaccines have proven safe and effective for the prevention of a spectrum of infectious diseases, many of which have mucocutaneous manifestations. In general, the role of vaccines is to boost immunity to a microbe before it infects the patient, thus preventing the disease. Therefore, almost all vaccines are prophylactic, not therapeutic. A recent exception to that rule, however, is the vaccine to prevent shingles. This vaccine helps prevent the reemergence of the varicella zoster virus, which often lies latently in the dorsal root ganglion for decades after the primary infection. Many physicians consider the greatest success story in medical history to be the elimination of smallpox, a disease that killed hundreds of millions of persons as recently as the 20th century. Although smallpox is the only infectious disease to have been officially eradicated, it is possible to eliminate certain other diseases (e.g., polio) that do not have reservoirs outside of humans. Elimination, or even control, of infectious diseases, however, cannot depend on vaccines alone. Public health measures (e.g., blood testing, safer sex/condoms, vector control, sewage and water treatment, isolation, and especially, education) are always necessary for the optimal benefits of vaccines. Although approved vaccines are much safer than the diseases they are designed to prevent, they must be used in the appropriate populations. For example, patients whose epidermal barriers are not intact should not receive vaccinia to prevent smallpox because of the potential of eczema vaccinatum. Furthermore, immunocompromised persons should not receive live attenuated vaccines because of possible dissemination. Much unfounded fear regarding vaccines, however, has led to poor compliance with recommended vaccines in certain communities, thus resulting in foci of outbreaks. The most notable example is the allegation that the measles/mumps/rubella vaccine causes autism, although numerous studies involving tens of thousands of children have proven otherwise. Currently, all existing vaccines are for the prevention of either viral or bacterial diseases. Vaccines are available to prevent the following viral diseases: measles, mumps, rubella, polio, hepatitis A, hepatitis B, influenza, rotavirus, rabies, monkeypox, smallpox, Japanese encephalitis, and yellow fever. Antibacterial vaccines include those for prevention of pertussis, tetanus, diphtheria, meningococcus, pneumococcus, Haemophilus influenza, cholera, typhoid, and anthrax. More money and effort has gone into the development of a vaccine to prevent infection with the human immunodeficiency virus than for any other vaccine, but thus far, no successful human immunodeficiency virus vaccine has been found. Vaccines are needed for a number of other bacterial and viral diseases, but no vaccines exist to prevent any fungal or protozoan diseases. Considering the marked morbidity and mortality associated with leishmaniasis and malaria, development of such vaccines is a very high priority. The two most recently approved vaccines that have direct relevance to dermatology are the shingles vaccine and the quadrivalent human papillomavirus (HPV) vaccine. Considering that herpes zoster affects over one million people in the United States each year, the shingles vaccine has much potential to reduce the morbidity of this disease. Because HPV types 16 and 18 are responsible for approximately 70% of cervical cancers, the second leading cause of cancer death in women worldwide, and the majority of other anogenital cancers, the HPV vaccine has great potential to