The importance of a multifaceted approach to characterizing the microbial flora of chronic wounds.

Chronic wounds contain complex polymicrobial communities of sessile organisms that have been underappreciated because of limitations of standard culture techniques. The aim of this work was to combine recently developed next-generation investigative techniques to comprehensively describe the microbial characteristics of chronic wounds. Tissue samples were obtained from 15 patients with chronic wounds presenting to the Johns Hopkins Wound Center. Standard bacteriological cultures demonstrated an average of three common bacterial species in wound samples. By contrast, high-throughput pyrosequencing revealed increased bacterial diversity with an average of 17 genera in each wound. Data from microbial community profiling of chronic wounds were compared with published sequenced analyses of bacteria from normal skin. Increased proportions of anaerobes, Gram-negative rods and Gram-positive cocci were found in chronic wounds. In addition, chronic wounds had significantly lower populations of Propionibacterium compared with normal skin. Using epifluorescence microscopy, wound bacteria were visualized in highly organized thick confluent biofilms or as scattered individual bacterial cells. Fluorescent in situ hybridization allowed for the visualization of Staphylococcus aureus cells in a wound sample. Quorum-sensing molecules were measured by bioassay to evaluate signaling patterns among bacteria in the wounds. A range of autoinducer-2 activities was detected in the wound samples. Collectively, these data provide new insights into the identity, organization, and behavior of bacteria in chronic wounds. Such information may provide important clues to effective future strategies in wound healing.

Case-based considerations in the treatment of actinic keratoses: utilizing combination or sequential therapy with 5-fluorouracil cream and destructive treatments.

Dermatologic conditions associated with prolonged sun exposure represent a substantial portion of visits to the dermatologist's office, particularly among elderly populations. Actinic keratoses are premalignant lesions that increase in frequency with each decade of life and have the potential to progress to squamous cell carcinoma. Non-melanoma skin cancers, such as squamous cell carcinoma and basal cell carcinoma, also represent sun-related conditions that require early and aggressive treatment. Therapeutic options for these conditions are abundant and range from topical field-directed therapies to destructive, lesion-directed procedures. Choice of therapy depends on the types and extent of lesions with which a patient presents; often, a combination of treatments provides the optimal means for successful outcomes. The following case-based review represents typical situations where multiple treatments were combined to manage actinic keratosis, squamous cell carcinoma and basal cell carcinoma in patients over an extended treatment period.

Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.

Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.

Photoaging.

This article discusses photoaging or premature skin aging from chronic ultraviolet exposure. This is an important cosmetic concern for many dermatologic patients. Clinical signs include rhytids, lentigines, mottled hyperpigmentation, loss of translucency, and decreased elasticity. These changes are more severe in individuals with fair skin and are further influenced by individual ethnicity and genetics. Photoaging may be prevented and treated with a variety of modalities, including topical retinoids, cosmeceuticals, chemical peels, injectable neuromodulators, soft tissue fillers, and light sources.

A practical approach to treating autoimmune bullous disorders with systemic medications.

The bullous diseases comprise a heterogeneous group of skin disorders with distinct clinical and histological findings. They are characterized histologically by clefts at varying depths in the skin and are pathologically caused either by congenital defects or autoantibodies. Autoimmune bullous disorders are chronic conditions with significant morbidity and mortality in untreated patients. With the advent of immunosuppressive medications, mortality from these diseases has decreased significantly. However, complications from therapy itself are common causes of morbidity in these patients. Therefore, treatment of autoimmune bullous diseases is a challenge, as patients must remain on chronic medications with side effects that limit their use. This article aims to provide a practical approach to understanding the available medications for the treatment of autoimmune bullous diseases.

Neoadjuvant imatinib therapy for dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is an unusual soft-tissue tumor with a propensity for subclinical extension and local recurrence. Surgical excision, even with tissue-sparing techniques, may cause significant deformity or disability because of the infiltrative nature of DFSP. In this study, we evaluate retrospective data obtained from 4 patients with locally advanced or recurrent DFSP who received neoadjuvant imatinib mesylate therapy before undergoing Mohs micrographic surgery. OBSERVATIONS: Patients treated with neoadjuvant imatinib therapy had an average tumor size reduction of 36.9%. This clinical response was paralleled by histopathologic changes, including decreased cellularity in 100% of the total area as well as significant hyalinization. Imatinib therapy for DFSP before Mohs micrographic surgery was associated with 100% local control at a maximum follow-up of 4 years. CONCLUSIONS: Neoadjuvant imatinib therapy is a well-tolerated, novel approach to DFSP that reduces tumor burden and facilitates resection. Larger prospective studies are needed to confirm and expand on these results.

What is the role of adjuvant radiotherapy in the treatment of cutaneous squamous cell carcinoma with perineural invasion?

BACKGROUND: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (SCC) is infrequent, occurring in 2.5% to 14% of patients, but it is important prognostically, because it carries an increased risk of recurrence and metastasis. Although both excision and Mohs micrographic surgery (MMS) are used to treat SCC with PNI, postoperative radiation therapy (XRT) often is recommended to minimize the risk of recurrence. To date, the effectiveness of adjuvant XRT in this setting has not been determined definitively. METHODS: The authors evaluated the effectiveness of adjuvant XRT in treating SCC with PNI by performing a thorough literature review. RESULTS: For SCC with PNI, the local control rate after MMS with or without XRT was from 92% to 100% compared with a control rate from 38% to 100% after standard excision with or without XRT. A better prognosis was associated with negative pretreatment magnetic resonance imaging or computed tomography findings than with positive radiographic evidence of PNI. Primary SCC with PNI was associated with better local control than recurrent SCC with PNI. When treatment outcomes were stratified by PNI type, SCC with microscopic PNI and SCC with extensive PNI had local control rates from 78% to 87% and from 50% to 55%, respectively. Adjuvant XRT was associated in selected patients with 100% local control. CONCLUSIONS: Few studies addressed the effectiveness of adjuvant XRT in patients who have SCC with PNI. Although XRT has been established as an adjuvant treatment for selected patients, the extent of nerve involvement by tumor, particularly in the setting of other high-risk features, may be helpful in defining its role. In the future, a multicentered, prospective, randomized clinical trial will be needed to assess the true efficacy of adjuvant XRT in the treatment of patients with SCC and PNI.