Faculty Bibliography

Pyoderma gangrenosum (PG) was first described by French Dermatologist Louis-Anne-Jean Brocq as a "rapidly spreading ulceration of soft tissue".¹ Histologically, PG is a neutrophilic dermatosis presenting as painful ulcerations. It is known to be associated with autoimmune-mediated disorders such as vasculitis.² Timely confirmatory diagnosis with tissue biopsy and management with immunosuppressive agents are critical.¹ We report a unique case of a PG-like lesion related to small vessel vasculitis in a 47-year-old man. Following the initiation of methotrexate therapy, the patient's lesions improved significantly, highlighting the importance of recognizing PG-like lesions associated with vasculitis.

We recently described the evolution of a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 variant responsible for an outbreak of skin and soft tissue infections. Acquisition of a mosaic version of the Φ11 prophage (mΦ11) that increases skin abscess size was an early step in CA-MRSA adaptation that primed the successful spread of the clone. The present report shows how prophage mΦ11 exerts its effect on virulence for skin infection without encoding a known toxin or fitness genes. Abscess size and skin inflammation were associated with DNA methylase activity of an mΦ11-encoded adenine methyltransferase (designated pamA). pamA increased expression of fibronectin-binding protein A (fnbA; FnBPA), and inactivation of fnbA eliminated the effect of pamA on abscess virulence without affecting strains lacking pamA. Thus, fnbA is a pamA-specific virulence factor. Mechanistically, pamA was shown to promote biofilm formation in vivo in skin abscesses, a phenotype linked to FnBPA's role in biofilm formation. Collectively, these data reveal a critical mechanism-epigenetic regulation of staphylococcal gene expression-by which phage can regulate virulence to drive adaptive leaps by S. aureus.

Contact dermatitis (CD) is a common and burdensome condition divided into irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). Treatment relies on accurate diagnosis and identification of the trigger, as definitive treatment is irritant/allergen avoidance. However, avoidance is not always possible, such as if the patient is reacting to a necessary medical device, if the trigger is integral to the patient's occupation, or if avoidance is practically untenable. In these cases, treatment is particularly challenging, especially as the literature on treatments in this clinical scenario is limited. Additionally, CD has a complex pathophysiology that varies according to trigger type, leading to variable treatment efficacy. This article reviews the current literature on treatments for CD with a focus on treatments when trigger avoidance is not feasible.

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H₂O₂, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic state in response to diminished metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δagr strains to lethal H₂O₂ doses. Increased survival of wild-type agr cells during H₂O₂ exposure required sodA, which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δagr cells from killing by H₂O₂. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived 'memory' of agr-mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Cybb

PURPOSE OF REVIEW/OBJECTIVE:Occupational hand dermatitis is a common work-related disorder of the skin. Prevention and management of this disease is critical to improving workers' quality of life and for occupation-specific retention. RECENT FINDINGS/RESULTS:This is a critical review of the current literature on occupational hand dermatitis. Occupational dermatitis continues to have a high prevalence among workers although the overall incidence may be slowly decreasing. Irritant contact dermatitis due to wet work exposure is the most common cause of occupational hand dermatitis. Healthcare workers, hairdressers, and metal workers are at particularly high risk for this disease. While some prevention programs have been ineffective in mitigating occupational hand dermatitis, other more resource-intensive initiatives may have benefit. Continued research is needed on ways to manage wet work exposures and on scalable, effective prevention programs for occupational hand dermatitis. The spectrum of culprit contact allergens continues to evolve, and vigilance for potential occupation-specific allergens remains important.