Incidence of Bacteremia, Infective Endocarditis, or Prosthetic Joint Infection in Dermatologic Surgery: A Systematic Review.

BACKGROUND: Prophylactic antibiotic therapy is widely used in dermatologic surgery to prevent surgical site infections and bacteremia, which can lead to prosthetic joint infections (PJI) and infective endocarditis (IE) in high-risk populations. OBJECTIVE: To evaluate the incidence of bacteremia, PJI, and IE after dermatologic surgery and assess the current evidence for antibiotic prophylaxis. MATERIALS AND METHODS: A search of the computerized bibliographic databases was performed using key terms from the date of inception to March 21, 2021. Data extraction was performed independently by 2 data extractors. RESULTS: The review resulted in 9 publications that met inclusion criteria, including 5 prospective cohort studies and 4 case reports or case series. The prospective studies reported a wide range of bacteremia incidence (0%-7%) after dermatologic surgery. No cases of PJI resulting directly from cutaneous surgery were identified, and only 1 case series reported IE after various skin procedures. CONCLUSION: These findings suggest a low rate of bacteremia and a lack of direct evidence linking dermatologic surgery to PJI or IE. The scarcity of published data on this topic is a limitation, highlighting the need for further research, particularly randomized controlled trials, to guide antibiotic prophylaxis recommendations.

Lipid rafts are required for effective renal D1 dopamine receptor function.

Effective receptor signaling is anchored on the preferential localization of the receptor in lipid rafts, which are plasma membrane platforms replete with cholesterol and sphingolipids. We hypothesized that the dopamine D1 receptor (D1 R) contains structural features that allow it to reside in lipid rafts for its activity. Mutation of C347 palmitoylation site and Y218 of a newly identified Cholesterol Recognition Amino Acid Consensus motif resulted in the exclusion of D1 R from lipid rafts, blunted cAMP response, impaired sodium transport, and increased oxidative stress in renal proximal tubule cells (RPTCs). Kidney-restricted silencing of Drd1 in C57BL/6J mice increased blood pressure (BP) that was normalized by renal tubule-restricted rescue with D1 R-wild-type but not the mutant D1 R 347A that lacks a palmitoylation site. Kidney-restricted disruption of lipid rafts by ß-MCD jettisoned the D1 R from the brush border, decreased sodium excretion, and increased oxidative stress and BP in C57BL/6J mice. Deletion of the PX domain of the novel D1 R-binding partner sorting nexin 19 (SNX19) resulted in D1 R partitioning solely to non-raft domains, while silencing of SNX19 impaired D1 R function in RPTCs. Kidney-restricted silencing of Snx19 resulted in hypertension in C57BL/6J mice. Our results highlight the essential role of lipid rafts for effective D1 R signaling.

Inner thigh friction as a cause of acne mechanica.

Acne mechanica is defined as being any acneiform eruption in areas of friction, pressure, stretching, rubbing, pinching, or occlusion of the skin in any individual, regardless of preexisting acne. Various causes have been reported, including prolonged back rest against a chair or bed, occlusive clothing, pressure from a prosthetic limb, and others. This is the first reported case of bilateral open comedones caused by inner thigh friction.

Epicutaneous Staphylococcus aureus induces IL-36 to enhance IgE production and ensuing allergic disease.

IgE induced by type 2 immune responses in atopic dermatitis is implicated in the progression of atopic dermatitis to other allergic diseases, including food allergies, allergic rhinitis, and asthma. However, the keratinocyte-derived signals that promote IgE and ensuing allergic diseases remain unclear. Herein, in a mouse model of atopic dermatitis-like skin inflammation induced by epicutaneous Staphylococcus aureus exposure, keratinocyte release of IL­36α along with IL-4 triggered B cell IgE class-switching, plasma cell differentiation, and increased serum IgE levels-all of which were abrogated in IL-36R-deficient mice or anti-IL­36R-blocking antibody-treated mice. Moreover, skin allergen sensitization during S. aureus epicutaneous exposure-induced IL-36 responses was required for the development of allergen-specific lung inflammation. In translating these findings, elevated IL­36 cytokines in human atopic dermatitis skin and in IL­36 receptor antagonist-deficiency patients coincided with increased serum IgE levels. Collectively, keratinocyte-initiated IL­36 responses represent a key mechanism and potential therapeutic target against allergic diseases.

Pathogenic and therapeutic role for NRF2 signaling in ultraviolet light-induced skin pigmentation.

Mottled skin pigmentation and solar lentigines from chronic photodamage with aging involve complex interactions between keratinocytes and melanocytes. However, the precise signaling mechanisms that could serve as therapeutic targets are unclear. Herein, we report that expression of nuclear factor erythroid 2-related factor 2 (NRF2), which regulates reduction-oxidation reactions, is altered in solar lentigines and photodamaged skin. Moreover, mottled skin pigmentation in humans could be treated with topical application of the NRF2 inducer sulforaphane (SF). Similarly, UV light-induced pigmentation of WT mouse ear skin could be treated or prevented with SF treatment. Conversely, SF treatment was unable to reduce UV-induced ear skin pigmentation in mice deficient in NRF2 or in mice with keratinocyte-specific conditional deletion of IL-6Rα. Taken together, NRF2 and IL-6Rα signaling are involved in the pathogenesis of UV-induced skin pigmentation, and specific enhancement of NRF2 signaling could represent a potential therapeutic target.

Preclinical Models and Methodologies for Monitoring Staphylococcus aureus Infections Using Noninvasive Optical Imaging.

In vivo whole-animal optical (bioluminescence and fluorescence) imaging of Staphylococcus aureus infections has provided the opportunity to noninvasively and longitudinally monitor the dynamics of the bacterial burden and ensuing host immune responses in live anesthetized animals. Herein, we describe several different mouse models of S. aureus skin infection, skin inflammation, incisional/excisional wound infections, as well as mouse and rabbit models of orthopedic implant infection, which utilized this imaging technology. These animal models and imaging methodologies provide insights into the pathogenesis of these infections and innate and adaptive immune responses, as well as the preclinical evaluation of diagnostic and treatment modalities. Noninvasive approaches to investigate host-pathogen interactions are extremely important as virulent community-acquired methicillin-resistant S. aureus strains (CA-MRSA) are spreading through the normal human population, becoming more antibiotic resistant and creating a serious threat to public health.

Development of a Staphylococcus aureus reporter strain with click beetle red luciferase for enhanced in vivo imaging of experimental bacteremia and mixed infections.

In vivo bioluminescence imaging has been used to monitor Staphylococcus aureus infections in preclinical models by employing bacterial reporter strains possessing a modified lux operon from Photorhabdus luminescens. However, the relatively short emission wavelength of lux (peak 490 nm) has limited tissue penetration. To overcome this limitation, the gene for the click beetle (Pyrophorus plagiophtalamus) red luciferase (luc) (with a longer >600 emission wavelength), was introduced singly and in combination with the lux operon into a methicillin-resistant S. aureus strain. After administration of the substrate D-luciferin, the luc bioluminescent signal was substantially greater than the lux signal in vitro. The luc signal had enhanced tissue penetration and improved anatomical co-registration with infected internal organs compared with the lux signal in a mouse model of S. aureus bacteremia with a sensitivity of approximately 3 × 104 CFU from the kidneys. Finally, in an in vivo mixed bacterial wound infection mouse model, S. aureus luc signals could be spectrally unmixed from Pseudomonas aeruginosa lux signals to noninvasively monitor the bacterial burden of both strains. Therefore, the S. aureus luc reporter may provide a technological advance for monitoring invasive organ dissemination during S. aureus bacteremia and for studying bacterial dynamics during mixed infections.

Immune and Inflammatory Reponses to Staphylococcus aureus Skin Infections.

PURPOSE OF REVIEW: There have been recent advances in our understanding of cutaneous immune responses to the important human skin pathogen, Staphylococcus aureus (S. aureus). This review will highlight these insights into innate and adaptive immune mechanisms in host defense and cutaneous inflammation in response to S. aureus skin infections. RECENT FINDINGS: Antimicrobial peptides, pattern recognition receptors and inflammasome activation function in innate immunity as well as T cells and their effector cytokines play a key role in adaptive immunity against S. aureus skin infections. In addition, certain mechanisms by which S. aureus contributes to aberrant cutaneous inflammation, such as in flares of the inflammatory skin disease atopic dermatitis have also been identified. SUMMARY: These cutaneous immune mechanisms could provide new targets for future vaccines and immune-based therapies to combat skin infections and cutaneous inflammation caused by S. aureus.

Profile of dupilumab and its potential in the treatment of inadequately controlled moderate-to-severe atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disorder that manifests as eczematous lesions, often associated with allergic rhinitis and asthma. Historically, moderate-to-severe disease has been managed with systemic immunosuppression, such as oral corticosteroids, which result in relapse and limiting side effects. Due to recent advancements in the identification of interleukin (IL)-4 and IL-13 as key mediators in AD, new biological agents have been developed for treatment. Dupilumab is a recently approved monoclonal antibody that targets the alpha subunit of the IL-4 receptor and, thus, downregulates activity of IL-4 and IL-13. This review discusses the profile of dupilumab and its potential for efficacy and safety in treating moderate-to-severe AD by reviewing data from Phase I-III clinical trials. Results suggest that dupilumab shows great therapeutic promise for AD. Further studies investigating extended use of dupilumab and dupilumab in comparison to other agents are needed to establish long-term efficacy and safety.