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.

Transitional cell neoplasm of the nasolacrimal duct associated with human papillomavirus type 11.

BACKGROUND: Tumors of the lacrimal sac are rare but noteworthy because of their significant potential to become malignant or life-threatening if treatment is delayed. Dermatologists may be the first to encounter such neoplasms. OBSERVATIONS: We report a case of a 53-year-old Caucasian woman who presented with a seven-year history of an asymptomatic, subcutaneous nodule near her right medial canthus. Histology of the lesion revealed transitional epithelium in a papillary growth pattern with numerous goblet cells, scattered mitoses and focal full-thickness atypia. The patient was diagnosed with transitional cell neoplasm (inverted papilloma-type) of the nasolacrimal duct. PCR evaluation identified HPV type 11 in the lesion. CONCLUSION: Our report is one of a growing number of case reports and series detecting HPV DNA in these tumors which further supports HPV as an etiologic agent in epithelial lacrimal sac tumors. We believe that dermatopathologists need to be aware of this entity, as dermatologists may be the first to encounter these neoplasms. LIMITATIONS: The association of HPV with this tumor does not prove causality.

Tropical dermatology: Tropical diseases caused by protozoa.

UNLABELLED: Protozoan infections are very common among tropical countries and have an important impact on public health. Leishmaniasis is the most widely disseminated protozoan infection in the world, while the trypanosomiases are widespread in both Africa and South America. Amebiasis, a less common protozoal infection, is a cause of significant morbidity in some regions. Toxoplasmosis and pneumocystosis (formerly thought to be caused by a protozoan) are worldwide parasitic infections with a very high incidence in immunocompromised patients but are not restricted to them. In the past, most protozoan infections were restricted to specific geographic areas and natural reservoirs. There are cases in which people from other regions may have come in contact with these pathogens. A common situation involves an accidental contamination of a traveler, tourist, soldier, or worker that has contact with a reservoir that contains the infection. Protozoan infections can be transmitted by arthropods, such as sandflies in the case of leishmaniasis or bugs in the case of trypanosomiases. Vertebrates also serve as vectors as in the case of toxoplasmosis and its transmission by domestic cats. The recognition of the clinical symptoms and the dermatologic findings of these diseases, and a knowledge of the geographic distribution of the pathogen, can be critical in making the diagnosis of a protozoan infection. LEARNING OBJECTIVES: After completing this learning activity, participants should be able to recognize the significance of protozoan infections worldwide, identify the dermatologic manifestations of protozoan infections, and select the best treatment for the patient with a protozoan infection.

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.

Vaccine immunology.

This article provides a review of immunology to enhance understanding of vaccine efficacy and use, and elaborates on the immune response to vaccination. The use of vaccines to prevent infectious diseases represents a tremendous accomplishment of biomedical science, especially considering the complex interplay of the immune system with innumerable pathogens. Vaccines have allowed for total eradication of one disease and have significantly reduced the incidence of other diseases. In order to have a successful vaccine-based eradication program, the infection must be limited to humans without an animal reservoir and only one or a few strains may exist in viral infection. These strains must have constant antigenic properties. A number of vaccine types exist, both traditional and innovative, and are described herein.

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.

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 plasmablastic 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.

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.

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.

Etanercept: an overview of its role in the treatment of psoriasis.

BACKGROUND: Psoriasis is a chronic and disabling disease affecting patients' quality of life. OBJECTIVES: Over the past decade, there has been significant growth in the knowledge of the proinflammatory pathways involved in psoriasis, including the role of increased levels of TNF. This knowledge has led to the increased use of biologic therapy, with such drugs as etanercept, a soluble TNF receptor fusion protein, aimed at inhibiting the actions of TNF. The goal of biologic generation is to provide selectively targeted therapy with fewer adverse events than traditional therapies. METHODS: Etanercept has been studied extensively and Phase III studies have been completed. CONCLUSION: Clinical data reviewed for etanercept-treated moderate to severe psoriasis have shown good efficacy, tolerability and a low adverse event profile.

Epidermodysplasia verruciformis and human papilloma virus.

PURPOSE OF REVIEW: Despite 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 FINDINGS: Susceptibility 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. SUMMARY: Discoveries 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.

Immunohistochemical localization of PDE10A in the rat brain.

PDE10A is a newly identified cAMP/cGMP phosphodiesterase for which mRNA is highly expressed in the mammalian striatum. In the present study, PDE10A protein and mRNA expression throughout the rat brain were determined, using a monoclonal antibody (24F3.F11) for Western blot and immunohistochemical analyses and an antisense riboprobe for in situ hybridization. High levels of mRNA are observed in most of the neuronal cell bodies of striatal complex (caudate n, n. accumbens and olfactory tubercle), indicating that PDE10A is expressed by the striatal medium spiny neurons. PDE10A-like immunoreactivity is dense throughout the striatal neuropil, as well as in the internal capsule, globus pallidus, and substantia nigra. These latter regions lack significant expression of PDE10A mRNA. Thus, PDE10A is transported throughout the dendritic tree and down the axons to the terminals of the medium spiny neurons. These data suggest a role for PDE10A in regulating activity within both the striatonigral and striatopallidal pathways. In addition, PDE10A immunoreactivity and mRNA are found at lower levels in the hippocampal pyramidal cell layer, dentate granule cell layer and throughout the cortex and cerebellar granule cell layer. Immunoreactivity is detected only in cell bodies in these latter regions. This more restricted subcellular localization of PDE10A outside the striatum suggests a second, distinct function for the enzyme in these regions.