Antibiotics and Imiquimod for Cutaneous T-Cell Lymphoma in Veterans: A Patient Population with Agent Orange Exposure.

LESSONS LEARNED: Staphylococcus aureus infection in cutaneous T-cell lymphoma (CTCL) is thought to contribute to disease progression; thus, adjunctive treatment with antibiotics warrants further investigation. This trial of antibiotic therapy followed by imiquimod in early stage CTCL was not completed because of difficulties with patient accrual. BACKGROUND: Cutaneous T-cell lymphoma (CTCL), a form of non-Hodgkin lymphoma, is a heterogeneous group of malignancies of mature memory T lymphocytes. It has an annual age-adjusted incidence of 7.5 per million persons in the U.S. population [1]. The etiology of CTCL is unknown, but epidemiological studies have reported potential associations with environmental and occupational factors, including Agent Orange exposure in Vietnam Veterans [2]. Both topical and systemic therapies have been identified as effective in CTCL; the choice of treatment is dependent on disease stage, with the overall goal of improving symptoms given the chronic and recurrent nature of the disease. Several studies have suggested that CTCL is exacerbated by the presence of Staphylococcus aureus in the skin and can be ameliorated by treatment with antibiotics [3]. METHODS: Our study was designed to assess the effects of antibiotics and imiquimod on early stage CTCL. Patients between the ages of 30-89 years with stage I and II CTCL were eligible for enrollment. They could not be receiving concurrent therapy, and the study design included a 14-day washout period after discontinuation of CTCL therapy. The washout period was followed by doxycycline 100 mg p.o. b.i.d. for 14 days and then two packets (250 mg per packet) of imiquimod 5% cream topically to the most clinically active lesions 3 days a week (Monday, Wednesday, and Friday) for 28 days. Skin lesions were measured using the modified Severity Weighted Assessment Tool (mSWAT). RESULTS: Our study enrolled only two patients with early stage CTCL because of difficulty locating patients with active CTCL able to discontinue all therapy. The two enrolled patients completed all therapy. One patient had a complete response after imiquimod, whereas the other patient had stable disease. CONCLUSION: Antibiotics and imiquimod have reported activity as single agents in CTCL; we did not enroll enough patients to assess value in the sequence of antibiotic therapy followed by imiquimod.

Diagnosis and treatment of tick infestation and tick-borne diseases with cutaneous manifestations.

Hard and soft ticks may be associated directly or indirectly with a number of dermatoses, both infectious and inflammatory in origin. Morbidity may occur as a result of tick bites, tick toxicosis, and even infestation. These arthropod vectors may transmit life-threatening protozoan, bacterial, rickettsial, and viral diseases with systemic and cutaneous findings. Additionally, ticks may transmit more than one pathogen with subsequent human coinfection. This article reviews the presentation of tick-borne illnesses and the medical management of these diseases. Among others, diseases such as ehrlichiosis, anaplasmosis, babesiosis, tularemia, borrelioses, tick-borne encephalitides, rickettsial spotted fevers, and tick typhus are discussed in this article. The recognition of skin manifestations associated with these diseases is paramount to early diagnosis and treatment initiation.

Mite infestations.

Mite infestations are important in dermatology because these may cause dermatologic diseases that range from papulosquamous eruptions to urticarial lesions to bullous eruptions and may spread infectious diseases. These clinical manifestations are important to recognize because mite-associated diseases may have systemic complications and may be confused with other dermatologic conditions. In treating mite infestations, oral antibiotics may be necessary. Prevention of infestation may be accomplished by pre-treating clothing with permethrin, using insect repellent N,N-Diethyl-meta-toluamide on clothing and skin, and treating animals infected with mites. This article will review etiology, clinical manifestation, and treatment of mite infestations.

Pravastatin-Induced Eczematous Eruption Mimicking Psoriasis.

BACKGROUND: Statins, an example of the most commonly prescribed medications to the elderly, are not without side effects. Dermatologic events are often overlooked as arising from medications, particularly those which are taken chronically. Moreover, elderly patients are prone to pharmacologic interactions due to multiple medications. In this report, we describe a case of a statin-induced eczematous dermatitis with a psoriasis-like clinical presentation and review the skin manifestations that may arise from statin therapy. CASE PRESENTATION: An 82-year-old man with gout and hypercholesterolemia presented to dermatology clinic with new onset of pruritic, scaly erythematous plaques bilaterally on the extensor surfaces of his arms. He had never had similar lesions before. Despite various topical and systemic treatments over several months, the rash continued to evolve. The patient was then advised to discontinue his long-term statin, which led to gradual resolution of his symptoms. He was subsequently diagnosed with statin-induced eczematous dermatitis. CONCLUSIONS: This case report describes an adverse cutaneous reaction to statins that is rarely reported in the literature. Medications, including longstanding therapies, should be suspected in cases of refractory dermatologic lesions.

Differential gene expression in abdomens of the malaria vector mosquito, Anopheles gambiae, after sugar feeding, blood feeding and Plasmodium berghei infection.

BACKGROUND: Large scale sequencing of cDNA libraries can provide profiles of genes expressed in an organism under defined biological and environmental circumstances. We have analyzed sequences of 4541 Expressed Sequence Tags (ESTs) from 3 different cDNA libraries created from abdomens from Plasmodium infection-susceptible adult female Anopheles gambiae. These libraries were made from sugar fed (S), rat blood fed (RB), and P. berghei-infected (IRB) mosquitoes at 30 hours after the blood meal, when most parasites would be transforming ookinetes or very early oocysts. RESULTS: The S, RB and IRB libraries contained 1727, 1145 and 1669 high quality ESTs, respectively, averaging 455 nucleotides (nt) in length. They assembled into 1975 consensus sequences--567 contigs and 1408 singletons. Functional annotation was performed to annotate probable molecular functions of the gene products and the biological processes in which they function. Genes represented at high frequency in one or more of the libraries were subjected to digital Northern analysis and results on expression of 5 verified by qRT-PCR. CONCLUSION: 13% of the 1965 ESTs showing identity to the A. gambiae genome sequence represent novel genes. These, together with untranslated regions (UTR) present on many of the ESTs, will inform further genome annotation. We have identified 23 genes encoding products likely to be involved in regulating the cellular oxidative environment and 25 insect immunity genes. We also identified 25 genes as being up or down regulated following blood feeding and/or feeding with P. berghei infected blood relative to their expression levels in sugar fed females.

Gene expression patterns associated with blood-feeding in the malaria mosquito Anopheles gambiae.

BACKGROUND: Blood feeding, or hematophagy, is a behavior exhibited by female mosquitoes required both for reproduction and for transmission of pathogens. We determined the expression patterns of 3,068 ESTs, representing ~2,000 unique gene transcripts using cDNA microarrays in adult female Anopheles gambiae at selected times during the first two days following blood ingestion, at 5 and 30 min during a 40 minute blood meal and at 0, 1, 3, 5, 12, 16, 24 and 48 hours after completion of the blood meal and compared their expression to transcript levels in mosquitoes with access only to a sugar solution. RESULTS: In blood-fed mosquitoes, 413 unique transcripts, approximately 25% of the total, were expressed at least two-fold above or below their levels in the sugar-fed mosquitoes, at one or more time points. These differentially expressed gene products were clustered using k-means clustering into Early Genes, Middle Genes, and Late Genes, containing 144, 130, and 139 unique transcripts, respectively. Several genes from each group were analyzed by quantitative real-time PCR in order to validate the microarray results. CONCLUSION: The expression patterns and annotation of the genes in these three groups (Early, Middle, and Late genes) are discussed in the context of female mosquitoes' physiological responses to blood feeding, including blood digestion, peritrophic matrix formation, egg development, and immunity.

Bacteriology of pressure ulcers in individuals with spinal cord injury: What we know and what we should know.

Individuals with spinal cord injury (SCI) are at increased risk for the development of pressure ulcers. These chronic wounds are debilitating and contribute to prolonged hospitalization and worse medical outcome. However, the species of bacteria and the role that specific species may play in delaying the healing of chronic pressure ulcers in the SCI population has not been well characterized. This study will review the literature regarding what is known currently about the bacteriology of pressure ulcers in individuals with SCI. An electronic literature search of MEDLINE (1966 to February 2014) was performed. Eleven studies detailing bacterial cultures of pressure ulcers in the SCI population met inclusion criteria and were selected for review. Among these studies, bacterial cultures were often polymicrobial with both aerobic and anaerobic bacteria identified with culture techniques that varied significantly. The most common organisms identified in pressure ulcers were Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, and Enterococcus faecalis. In general, wounds were poorly characterized with minimal to no physical description and/or location provided. Our present understanding of factors that may alter the microbiome of pressure ulcers in individuals with SCI is quite rudimentary, at best. Well-designed studies are needed to assess appropriate wound culture technique, the impact of bacterial composition on wound healing, development of infection, and the optimum medical and surgical approaches to wound care.

Comparative analysis of the global transcriptome of Anopheles funestus from Mali, West Africa.

BACKGROUND: Anopheles funestus is a principal vector of malaria across much of tropical Africa and is considered one of the most efficient of its kind, yet studies of this species have lagged behind those of its broadly sympatric congener, An. gambiae. In aid of future genomic sequencing of An. funestus, we explored the whole body transcriptome, derived from mixed stage progeny of wild-caught females from Mali, West Africa. PRINCIPAL FINDINGS: Here we report the functional annotation and comparative genomics of 2,005 expressed sequence tags (ESTs) from An. funestus, which were assembled with a previous EST set from adult female salivary glands from the same mosquito. The assembled ESTs provided for a nonredundant catalog of 1,035 transcripts excluding mitochondrial sequences. CONCLUSIONS/SIGNIFICANCE: Comparison of the An. funestus and An. gambiae transcriptomes using computational and macroarray approaches revealed a high degree of sequence identity despite an estimated 20-80 MY divergence time between lineages. A phylogenetically broader comparative genomic analysis indicated that the most rapidly evolving proteins--those involved in immunity, hematophagy, formation of extracellular structures, and hypothetical conserved proteins--are those that probably play important roles in how mosquitoes adapt to their nutritional and external environments, and therefore could be of greatest interest in disease control.