Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease.

Chemokines play critical roles in the recruitment and activation of immune cells in both homeostatic and pathologic conditions. Here, we examined chemokine ligand-receptor pairs to better understand the immunopathogenesis of cutaneous lupus erythematosus (CLE), a complex autoimmune connective tissue disorder. We used suction blister biopsies to measure cellular infiltrates with spectral flow cytometry in the interface dermatitis reaction, as well as 184 protein analytes in interstitial skin fluid using Olink targeted proteomics. Flow and Olink data concordantly demonstrated significant increases in T cells and antigen presenting cells (APCs). We also performed spatial transcriptomics and spatial proteomics of punch biopsies using digital spatial profiling (DSP) technology on CLE skin and healthy margin controls to examine discreet locations within the tissue. Spatial and Olink data confirmed elevation of interferon (IFN) and IFN-inducible CXCR3 chemokine ligands. Comparing involved versus uninvolved keratinocytes in CLE samples revealed upregulation of essential inflammatory response genes in areas near interface dermatitis, including AIM2. Our Olink data confirmed upregulation of Caspase 8, IL-18 which is the final product of AIM2 activation, and induced chemokines including CCL8 and CXCL6 in CLE lesional samples. Chemotaxis assays using PBMCs from healthy and CLE donors revealed that T cells are equally poised to respond to CXCR3 ligands, whereas CD14+CD16+ APC populations are more sensitive to CXCL6 via CXCR1 and CD14+ are more sensitive to CCL8 via CCR2. Taken together, our data map a pathway from keratinocyte injury to lymphocyte recruitment in CLE via AIM2-Casp8-IL-18-CXCL6/CXCR1 and CCL8/CCR2, and IFNG/IFNL1-CXCL9/CXCL11-CXCR3.

A dermatologic assessment of 101 mpox (monkeypox) cases from 13 countries during the 2022 outbreak: Skin lesion morphology, clinical course, and scarring.

BACKGROUND: In the 2022 mpox (monkeypox) outbreak, 79,000 global cases have been reported. Yet, limited dermatologic data have been published regarding lesion morphology and progression. OBJECTIVE: The objective of this study was to characterize skin lesion morphology, symptomatology, and outcomes of mpox infection over time. METHODS: The American Academy of Dermatology/International League of Dermatological Societies Dermatology COVID-19, Mpox, and Emerging Infections Registry captured deidentified patient cases of mpox entered by health care professionals. RESULTS: From August 4 to November 13, 2022, 101 cases from 13 countries were entered, primarily by dermatologists (92%). Thirty-nine percent had fewer than 5 lesions. In 54% of cases, skin lesions were the first sign of infection. In the first 1-5 days of infection, papules (36%), vesicles (17%), and pustules (20%) predominated. By days 6-10, pustules (36%) were most common, followed by erosions/ulcers (27%) and crusts/scabs (24%). Crusts/scabs were the predominant morphology after day 11. Ten cases of morbilliform rash were reported. Scarring occurred in 13% of the cases. LIMITATIONS: Registry-reported data cannot address incidence. There is a potential reporting bias from the predilection to report cases with greater clinical severity. DISCUSSION: These findings highlight differences in skin findings compared to historical outbreaks, notably the presence of skin lesions prior to systemic symptoms and low overall lesion counts. Scarring emerged as a major possible sequela.

Stellate Hypopigmentation in a Pediatric Patient After Treatment with Intralesionally-Injected Corticosteroid.

BACKGROUND Several factors contribute to keloids in post-operative patients, including skin mechanics, genetics, and inflammatory processes. One of the most widely used treatment modalities for keloidal scars involves the intralesional injection of corticosteroids, such as triamcinolone acetonide (TAC). TAC is a first-line treatment option for keloids due to its proven efficacy and effectiveness in reducing collagen synthesis, glycosaminoglycan synthesis, inflammatory processes, and proliferation of fibroblasts. Some common adverse effects of intralesional corticosteroid injection include localized hypopigmentation, depigmentation, skin atrophy, and lipoatrophy. CASE REPORT In this report, we describe the case of a 3-year-old African American male patient who presented for dermatologic evaluation of a diffused stellate hypopigmentation attributed to intralesional corticosteroid injection following a keloid removal. Specifically, we summarize this case's clinical features, diagnosis, and outcomes. CONCLUSIONS The case illustrates self-limiting hypopigmentation that repigmented successfully without clinical intervention. Although previous reports of corticosteroid injections' adverse effects resulting in hypopigmentation have been published, this condition is uncommon or poorly reported in pediatric patients. This report aims to contribute to our understanding of the effects of administering corticosteroids in pediatric patients by virtue of diversifying the cases reported in the currently available literature.

Medicinal Plant Extracts and Natural Compounds for the Treatment of Cutaneous Lupus Erythematosus: A Systematic Review.

Cutaneous lupus erythematosus (CLE) is a group of autoimmune connective tissue disorders that significantly impact quality of life. Current treatment approaches typically use antimalarial medications, though patients may become recalcitrant. Other treatment options include general immunosuppressants, highlighting the need for more and more targeted treatment options. The purpose of this systematic review was to identify potential compounds that could be repurposed for CLE from natural products since many rheumatologic drugs are derived from natural products, including antimalarials. This study was registered with PROSPERO, the international prospective register of systematic reviews (registration number CRD42021251048). We comprehensively searched Ovid Medline, Cochrane Library, and Scopus databases from inception to April 27th, 2021. These terms included cutaneous lupus erythematosus; general plant, fungus, bacteria terminology; selected plants and plant-derived products; selected antimalarials; and JAK inhibitors. Our search yielded 13,970 studies, of which 1,362 were duplicates. We screened 12,608 abstracts, found 12,043 to be irrelevant, and assessed 565 full-text studies for eligibility. Of these, 506 were excluded, and 59 studies were included in the data extraction. The ROBINS-I risk of bias assessment tool was used to assess studies that met our inclusion criteria. According to our findings, several natural compounds do reduce inflammation in lupus and other autoimmune skin diseases in studies using in vitro methods, mouse models, and clinical observational studies, along with a few randomized clinical trials. Our study has cataloged evidence in support of potential natural compounds and plant extracts that could serve as novel sources of active ingredients for the treatment of CLE. It is imperative that further studies in mice and humans are conducted to validate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=251048.

The Impact of the Circadian Clock on Skin Physiology and Cancer Development.

Skin cancers are growing in incidence worldwide and are primarily caused by exposures to ultraviolet (UV) wavelengths of sunlight. UV radiation induces the formation of photoproducts and other lesions in DNA that if not removed by DNA repair may lead to mutagenesis and carcinogenesis. Though the factors that cause skin carcinogenesis are reasonably well understood, studies over the past 10-15 years have linked the timing of UV exposure to DNA repair and skin carcinogenesis and implicate a role for the body's circadian clock in UV response and disease risk. Here we review what is known about the skin circadian clock, how it affects various aspects of skin physiology, and the factors that affect circadian rhythms in the skin. Furthermore, the molecular understanding of the circadian clock has led to the development of small molecules that target clock proteins; thus, we discuss the potential use of such compounds for manipulating circadian clock-controlled processes in the skin to modulate responses to UV radiation and mitigate cancer risk.

Life after lockdown: Zooming out on perceptions in the post-videoconferencing era.

BACKGROUND: The COVID-19 pandemic has deeply disrupted daily life across the globe, with profound effects on mental and physical health. After more than a year of isolation and communication via videoconferencing, people are returning to in-person activities. OBJECTIVE: This study aimed to investigate worsening self-perception, mental health, and anxiety with the return to in-person activities, with a focus on the influence of videoconferencing, social media, and the use of filters. METHODS: An anonymous survey was distributed online through social media platforms and student network pages. RESULTS: A total of 7295 participants responded to the survey. Seventy-one precent reported anxiety or stress related to returning to in-person activities, and nearly 64% sought mental health support services. Thirty-percent stated they plan to invest in their appearance as a coping strategy to deal with the anxiety of returning to in-person, and >30% plan to take action in changing their appearance. The most reported dermatologic concerns were skin discoloration (32.36%), wrinkles (24.45%), and acne (14.85%). The prevalence of anxiety and mental health services increased relative to the use of filters in 18- to 24 year-olds. CONCLUSION: This survey study of >7000 participants across the country elucidates worsening self-perception, anxiety, and mental health as we return to in-person activities in relation to increased videoconferencing, social media usage, and the use of filters. Physicians should be aware of these effects to better serve their patients.