Efficacy of synthetic peptides RP-1 and AA-RP-1 against Leishmania species in vitro and in vivo.

Host defense peptides are naturally occurring molecules that play essential roles in innate immunity to infection. Based on prior structure-function knowledge, we tested two synthetic peptides (RP-1 and AA-RP-1) modeled on the conserved, microbicidal α-helical domain of mammalian CXCL4 platelet kinocidins. These peptides were evaluated for efficacy against Leishmania species, the causative agents of the group of diseases known as leishmaniasis. In vitro antileishmanial activity was assessed against three distinct Leishmania strains by measuring proliferation, metabolic activity and parasite viability after exposure to various concentrations of peptides. We demonstrate that micromolar concentrations of RP-1 and AA-RP-1 caused dose-dependent growth inhibition of Leishmania promastigotes. This antileishmanial activity correlated with rapid membrane disruption, as well as with a loss of mitochondrial transmembrane potential. In addition, RP-1 and AA-RP-1 demonstrated distinct and significant in vivo antileishmanial activities in a mouse model of experimental visceral leishmaniasis after intravenous administration. These results establish efficacy of RP-1 lineage synthetic peptides against Leishmania species in vitro and after intravenous administration in vivo and provide further validation of proof of concept for the development of these and related systemic anti-infective peptides targeting pathogens that are resistant to conventional antibiotics.

Imiquimod: a review of off-label clinical applications.

The immunomodulatory characteristics and topical application of imiquimod (IQ), a toll-like receptor 7 agonist, have lead to extensive off-label therapeutic trials. Off-label use is not uncommon in dermatology. However, clinicians must make informed decisions to ensure safe and effective implementation when standardized protocols are lacking. We present the highest level of clinical evidence for each off-label application of IQ, summarize management steps, treatment regimens, and results. We hope consolidation of this information will facilitate implementation of informed and evidence-based clinical decisions. Forty-six off-label applications were reported. Treatments were generally applied in the same manner, tailored to induce an inflammatory response and reduced with the development of adverse reactions. The efficacy of imiquimod ranged from promising to suboptimal compared to standard treatments and protocols. Clinicians who choose to use IQ off-label should have a firm understanding of the extent an application has been studied and how to manage adverse events.

Diagnostic accuracy in patients admitted to hospitals with cellulitis.

Misdiagnosis of non-infectious conditions such as cellulitis is a common error and can result in unnecessary hospitalization and antibiotic use. We sought to prospectively determine the misdiagnosis rate of cellulitis among hospitalized patients and to determine if a visually-based computerized diagnostic decision support system (VCDDSS, also named VisualDx) could generate an improved differential diagnosis (DDx) for misdiagnosed patients. In two separate institutions, attending dermatologists or infectious disease specialists evaluated all consecutive patients hospitalized for "cellulitis" by the emergency department. Among 145 subjects enrolled, misdiagnosis occurred in 41 (28%) patients. The diagnosis most commonly mistaken as cellulitis was stasis dermatitis (37%). At one center, in cases that were misdiagnosed by the emergency department, the VCDDSS included the correct diagnosis in the DDx more frequently than the admitting team (18/28 cases (64%) compared to 4/28 cases (14%), p=0.0003). These results demonstrate the capability of this VCDDSS to assist primary care physicians with generating a more accurate DDx when confronted with patients presenting with possible skin infections. Misdiagnoses may result in a significant source of healthcare costs and misdiagnosis-related patient harm. Inclusion of decision support tools early in the diagnostic workflow may reduce misdiagnosis and result in more efficient healthcare management.

Cutaneous and mucocutaneous leishmaniasis.

Leishmaniasis is a cluster of diseases caused by protozoa in the genus Leishmania. There are three basic clinical forms: cutaneous, mucocutaneous, and visceral leishmaniasis. The present review focuses on the diagnosis and treatment of cutaneous and mucocutaneous leishmaniasis. Characteristics of both the human host and the parasite species influence the clinical disease manifestations that range from asymptomatic exposure, to self-healing skin ulcers, to life-threatening widespread destructive ulcerations. Whether through medical treatment or through spontaneous resolution, skin ulcerations generally result in disfiguring scars with significant social and economic impact. Tests to confirm the diagnosis should be performed on patients who have recently visited endemic areas and have skin or mucosal manifestations consistent with leishmaniasis. Treatment depends on the species of Leishmania and the risk of widespread or disfiguring disease. Because of increasing trends in global travel, educating health care providers to recognize and treat leishmaniasis in both endemic and non-endemic countries is imperative.

Innovative Surgical Approaches and Selection Criteria of Large Acne Keloidalis Nuchae Lesions.

BACKGROUND: Acne keloidalis nuchae is a debilitating condition mainly affecting the occipital region or nape of the neck. Surgical approaches are limited in aesthetic outcomes. Three innovative surgical approaches based on selection criteria are presented for enhanced and more predictable wound healing and posterior hairline cosmesis. METHODS: "Bat excision" and secondary intention healing are shown for 2 of 37 representative patients and confined to the area between the occipital protuberance superiorly and posterior hairline inferiorly. Lesions with ≤3 cm vertical width were required to be in the lower one-half portion of this zone. The same procedure was aided by the use of tension sutures for lesions with >3 cm vertical width area within the defined zone. It was also suitable for breaches of the 2 horizontal lines defined above but generally located in the nuchal area. Debridement of premature epithelizing granulation tissue is shown in 2 additional patients. RESULTS: Use of these procedures with debridement in selected patients allowed fine control over the hairline shape and resulted in narrower scars. The mean maximum sagittal width of excised lesions was 5.4 cm. Excised lesion width ≥6.5 cm was highly predictive of >2.5 cm wide scar (P = 0.001). CONCLUSION: Innovative procedures based on selection criteria can extend the approach of acne keloidalis nuchae excision with secondary intention healing to better control the final hairline shape and minimize scarring.

Using Network Oriented Research Assistant (NORA) Technology to Compare Digital Photographic With In-Person Assessment of Acne Vulgaris.

Importance: Teledermatology has undergone exponential growth in the past 2 decades. Many technological innovations are becoming available without necessarily undergoing validation studies for specific dermatologic applications. Objective: To determine whether patient-taken photographs of acne using Network Oriented Research Assistant (NORA) result in similar lesion counts and Investigator's Global Assessment (IGA) findings compared with in-person examination findings. Design, Setting, and Participants: This pilot reliability study enrolled consecutive patients with acne vulgaris from a single general dermatology practice in Los Angeles, California, who were able to use NORA on an iPhone 6 to take self-photographs. Patients were enrolled from January 1 through March 31, 2016. Each individual underwent in-person and digital evaluation of his or her acne by the same dermatologist. A period of at least 1 week separated the in-person and digital assessments of acne. Interventions: All participants were trained on how to use NORA on the iPhone 6 and take photographs of their face with the rear-facing camera. Main Outcomes and Measures: Reliability of patient-taken photographs with NORA for acne evaluation compared with in-person examination findings. Acne assessment measures included lesion count (total, inflammatory, noninflammatory, and cystic) and IGA for acne severity. Results: A total of 69 patients (37 male [54%] and 32 female [46%]; mean [SD] age, 22.7 [7.7] years) enrolled in the study. The intraclass correlation coefficients of in-person and photograph-based acne evaluations indicated strong agreement. The intraclass correlation coefficient for total lesion count was 0.81; for the IGA, 0.75. Inflammatory lesion count, noninflammatory lesion count, and cyst count had intraclass correlation coefficients of 0.72, 0.72, and 0.82, respectively. Conclusions and Relevance: This study found agreement between acne evaluations performed in person and from self-photographs with NORA. As a reliable telehealth technology for acne, NORA can be used as a teledermatology platform for dermatology research and can increase access to dermatologic care.