Risk factors for the development of acne in healthcare workers during the COVID-19 pandemic.

The COVID-19 pandemic has led to many healthcare workers having prolonged contact with tight-fitting masks, leading to maskne. "Maskne" is defined as acne secondary to mask use. There are limited studies on maskne during the COVID-19 pandemic. The objective of this study is to identify risk factors for the development of maskne amongst healthcare workers. A cross-sectional survey was completed by 227 medical students, resident physicians, and nursing students at Johns Hopkins Medicine, with 68.7% of participants reporting development of maskne. Surgical masks and respirators were the most prevalent mask types worn at work. The most common prevention methods were the use of mild cleansers and moisturizers. Chi-squared analysis was used for data analysis. The results of this study indicate that gender (p = 0.003) and duration of mask use (p = 0.048) are significant risk factors for maskne development. These factors are non-modifiable, but may be used for more targeted education for prevention.

Time to treatment and complexity of Mohs micrographic surgery.

The impact of time to treatment (TTT) on the surgical management of keratinocyte carcinoma, specifically the complexity of Mohs micrographic surgery (MMS), is incompletely understood. We performed a retrospective chart review of patients undergoing MMS for keratinocyte carcinoma between July 1, 2019 and February 28, 2021 to examine associations between TTT and surgical characteristics. The median TTT for the 1571 patients treated with MMS during the study period was 42 days (interquartile range 28-61 days). In adjusted analyses, increasing TTT was not associated with increasing utilization of flap or graft repairs. Although a 42-day increase in TTT was associated with a 17.6 mm2 increase in the post-operative surgical defect size after MMS, TTT was not associated with linear repair length or flap/graft repair area. In conclusion, TTT was not independently associated with the type of repair or repair length after MMS, suggesting that the complexity of Mohs reconstruction is not influenced by TTT within the time range studied in this cohort.

Cutaneous Surgical Wounds Have Distinct Microbiomes from Intact Skin.

Infections are relatively rare following cutaneous surgical procedures, despite the potential for wound exposure to pathogens both during surgery and throughout the healing process. Although gut commensals are believed to reduce the risk of intestinal infections, an analogous role for skin commensals has not been described. In fact, the microbiome of normally healing surgical skin wounds has not yet been profiled using culture-independent techniques. We characterized the wound microbiome in 53 patients who underwent skin cancer surgery and healed without signs or symptoms of infection. A week after surgery, several bacterial species displayed significant differences in relative abundance when compared to control, nonoperated skin from the same patient. The relative abundance of the most common bacterium found on intact skin, Cutibacterium acnes, was reduced in wounds 5-fold. Staphylococcus aureus, a frequent cause of postoperative skin infections, was enriched 6.4-fold in clinically noninfected wounds, suggesting active suppression of pathogenicity. Finally, members of the Corynebacterium genus were the dominant organism in postoperative wounds, making up 37% of the average wound microbiome. The enrichment of these bacteria in normally healing wounds suggests that they might be capable of providing colonization resistance. Future studies focused on the biological and clinical significance of the wound microbiome may shed light on normal wound healing and potential therapeutic opportunities to mitigate infection risk. IMPORTANCE Commensal bacteria on skin may limit the ability of pathogenic bacteria to cause clinically significant infections. The bacteria on healing acute wounds, which might provide such a protective effect, have not been described using culture-independent approaches in the absence of antibiotics. We compare the microbiome of wounds a week after skin cancer removal surgery with intact skin from the same patient. We find that the potentially pathogenic species S. aureus is common on these healing wounds despite the absence of symptoms or signs of infection. We report that bacteria often considered as potential skin probiotics, including Staphylococcus epidermidis, do not reach high relative abundance in wound microbiomes. In contrast, specific members of the Corynebacterium genus, rarely associated with infections, were significantly enriched in healing wounds compared to intact skin. Future work is needed to see if Corynebacterium species or derivatives thereof could be employed to lower the risk of wound infection.

STAT3 protein promotes T-cell survival and inhibits interleukin-2 production through up-regulation of Class O Forkhead transcription factors.

Much is known about the role of STAT3 in regulating differentiation of interleukin-17-producing Th17 cells, but its function in other lymphocyte subsets is not well understood. In this report, we reveal wide-ranging functions of STAT3 in T-cells and provide evidence that STAT3 is convergence point for mechanisms that regulate lymphocyte quiescence and those controlling T-cell activation and survival. We show here that STAT3 inhibits T-lymphocyte proliferation by up-regulating the expression of Class-O Forkhead transcription factors, which play essential roles in maintaining T-cells in quiescent state. We further show that STAT3 binds directly to FoxO1 or FoxO3a promoter and that STAT3-deficiency resulted in down-regulation of the expression of FoxO1, FoxO3a and FoxO-target genes (IκB and p27Kip1). Compared with wild-type T-cells, STAT3-deficient T-cells produced more IL-2, due in part, to marked decrease in IκB-mediated sequestration of NF-κB in the cytoplasm and resultant enhancement of NF-κB activation. However, the high level of IL-2 production by STAT3-deficient T-cells was partially restored to normal levels by overexpressing FoxO1. It is notable that their exaggerated increase in IL-2 production rendered STAT3-deficient lymphocytes more susceptible to activation-induced cell death, suggesting that STAT3 might protect T-cells from apoptosis by limiting their production of IL-2 through up-regulation of FoxO1/FoxO3a expression. Moreover, we found that STAT3 enhanced survival of activated T-cells by up-regulating OX-40 and Bcl-2 while down-regulating FasL and Bad expression, suggesting that similar to role of FoxOs in regulating the lifespan of worms, STAT3 and FoxO pathways converge to regulate lifespan of T-lymphocytes.

Persistence of IL-2 expressing Th17 cells in healthy humans and experimental autoimmune uveitis.

Compared with other T-helper subsets, Th17 cell numbers are very low in human blood but become elevated in chronic inflammatory diseases. In this study, we investigated mechanisms that may explain the frequent involvement of Th17 cells in autoimmune diseases such as uveitis. We compared Th17 and Th1 subsets and found that Th17 cells expressed lower IL-2 levels during Ag-priming and this correlated with their decreased susceptibility to activation-induced cell death (AICD). However, complete depletion of IL-2 with IL-2 neutralizing antibodies rendered Th17 cells as susceptible to apoptosis as Th1 cells, suggesting that the low levels of IL-2 produced by Th17 cells conferred survival advantages to this subset. We describe here a Th17 subtype that constitutively produces very low levels of IL-2 (Th17-DP). The Th17-DP population increased dramatically in the blood and retina of mice during experimental autoimmune uveitis, indicating their potential involvement in the etiology of uveitis. We further show that the majority of the memory Th17 cells in human blood are Th17-DP and are targets of daclizumab, an IL-2R antibody used in treating recalcitrant uveitis. Thus, Th17 cells may persist in tissues and contribute to chronic inflammation by limiting IL-2 production to levels that cannot provoke IL-2-induced AICD yet are sufficient to promote Th17 homeostatic expansion.

Pruritus in Black Skin: Unique Molecular Characteristics and Clinical Features.

BACKGROUND: Chronic pruritus dramatically disrupts quality of life, impairs sleep, and is difficult to treat. The pathogenesis and severity of chronic itch can vary significantly with race. Black skin has inherent structural and molecular characteristics that exacerbates pruritus, leading to unique presentations of pruritic conditions and added challenges in finding effective therapies. The aim of this review is to discuss structural variances in black skin, the subsequent epidemiological disparities in chronic pruritic conditions, and clinical management pearls for the management of itch in black patients. METHODS: Current literature including mechanistic, translational, and epidemiological data on racial differences in pruritus focusing on black skin were reviewed in Pubmed. FINDINGS: Black skin has several unique structural properties related to the pathogenesis of pruritus, including increased trans-epidermal water loss, decreased ceramide levels, lower pH in the stratum corneum, and increased size of mast cells. Black patients consequently are disproportionately affected by chronic pruritic disorders including atopic dermatitis, prurigo nodularis, HIV-related pruritic dermatoses, and cutaneous T-cell lymphoma. CONCLUSION: Pruritus and chronic pruritus disorders disproportionately affects black patients. Management of pruritus of special importance in black patients includes low pH skin care products to protect the skin barrier along with emollients to diminish trans-epidermal water loss. Further mechanistic studies are needed to characterize racial differences in biomarkers and therapeutic targets of chronic itch.

Transcriptomic analysis of atopic dermatitis in African Americans is characterized by Th2/Th17-centered cutaneous immune activation.

Atopic dermatitis (AD) often presents more severely in African Americans (AAs) and with greater involvement of extensor areas. To investigate immune signatures of AD in AAs with moderate to severe pruritus, lesional and non-lesional punch biopsies were taken from AA patients along with age-, race-, and sex-matched controls. Histology of lesional skin showed psoriasiform dermatitis and spongiotic dermatitis, suggesting both Th2 and Th17 activity. Gene Set Variation Analysis showed upregulation of Th2 and Th17 pathways in both lesional versus non-lesional and lesional versus control (p < 0.01), while Th1 and Th22 upregulation were observed in lesional versus control (p < 0.05). Evidence for a broad immune signature also was supported by upregulated Th1 and Th22 pathways, and clinically may represent greater severity of AD in AA. Furthermore, population-level analysis of data from TriNetX, a global federated health research network, revealed that AA AD patients had higher values for CRP, ferritin, and blood eosinophils compared to age-, sex-, and race-matched controls as well as white AD patients, suggesting broad systemic inflammation. Therefore, AA AD patients may feature broader immune activation than previously thought and may derive benefit from systemic immunomodulating therapies that modulate key drivers of multiple immune pathways.

Disseminated Eruptive Blue Nevi in a Young Adult Patient.

Common blue nevi tend to be singular or localized, with multiple eruptive blue nevi being a rare occurrence. We report the case of a young adult who presented with multiple asymptomatic lesions that had appeared gradually over a few years. Physical examination revealed 30 distinct, blue-gray macules diffusely over the medial buttocks, lower back, and dorsal arms. Histopathology showed pigmented dendritic melanocytes with associated melanophages, features characteristic of blue nevus. This case demonstrates that eruptive blue nevi can present as numerous, disseminated lesions over multiple anatomic sites. Recognition of the various patterns of eruptive blue nevi and their benign nature can reduce unnecessary biopsies and work-up.

Suppressor of cytokine signaling-1 (SOCS1) inhibits lymphocyte recruitment into the retina and protects SOCS1 transgenic rats and mice from ocular inflammation.

PURPOSE: Suppressors of cytokine signaling (SOCS) proteins regulate the intensity and duration of cytokine signals and defective expression of SOCS1 and SOCS3 has been reported in a number of human diseases. The purpose of this study was to investigate the role of SOCS1 in intraocular inflammatory diseases (uveitis) and whether SOCS1 expression is defective in patients with ocular inflammatory diseases. METHODS: Blood from patients with scleritis or healthy human volunteers was analyzed for SOCS expression by RNase protection assay and RT-PCR. The authors generated SOCS1 transgenic rats and mice (SOCS1-Tg), induced experimental autoimmune uveoretinitis (EAU) by active immunization with interphotoreceptor retinal binding protein or adoptive transfer of uveitogenic T cells, and investigated effects of SOCS1 overexpression on EAU. SOCS1-mediated protection of retinal cells from apoptosis was assessed by annexin V staining. RESULTS: Induction of cytokine-induced SH2 protein was comparable between patients and volunteers, whereas 80% of lymphocytes from patients with scleritis failed to induce SOCS1 in response to IL-2. Compared with wild-type littermates, SOCS1-Tg rats/mice developed less severe EAU. Constitutive overexpression of SOCS1 in retina inhibited expression of chemokines (CCL17, CCL20, CXCL9, CXCL10), reduced Th17/Th1 expansion, and inhibited recruitment of inflammatory cells into the retina. The authors also show that SOCS1 protected retinal cells from staurosporine as well as H2O2-induced apoptosis. CONCLUSIONS: Defective expression of SOCS1 in patients with scleritis, taken together with SOCS1-mediated protection of neuroretinal cells from apoptosis, suggest that SOCS1 has neuroprotective function in the retina, implying that administration of SOCS1 mimetic peptides may be useful in treating uveitis or scleritis.