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    • J Dermatolog Treat. 2021 Jul 22:1-8. doi: 10.1080/09546634.2021.1959507. Online ahead of print. NO ABSTRACT PMID:34291712 | DOI:10.1080/09546634.2021.1959507 {url} = URL to article
    • Front Immunol. 2021 Jul 5;12:674871. doi: 10.3389/fimmu.2021.674871. eCollection 2021. ABSTRACT Rosacea is a common chronic inflammatory condition that mainly affects the central face. However, the molecular background of the normal central face and the transcriptional profiling and immune cell composition of rosacea lesions remain largely unknown. Here, we performed whole-skin and epidermal RNA-seq of central facial skin from healthy individuals, lesions and matched normal skin from rosacea patients. From whole-skin RNA-seq, the site-specific gene signatures for central facial skin were mainly enriched in epithelial cell differentiation, with upregulation of the activator protein-1 (AP1) transcription factor (TF). We identified the common upregulated inflammatory signatures and diminished keratinization signature for rosacea lesions. Gene ontology, pathway, TF enrichment and immunohistochemistry results suggested that STAT1 was the potential core of the critical TF networks connecting the epithelial-immune crosstalk in rosacea lesions. Epidermal RNA-seq and immunohistochemistry analysis further validated the epithelial-derived STAT1 signature in rosacea lesions. The epidermal STAT1/IRF1 signature was observed across ETR, PPR, and PhR subtypes. Immune cell composition revealed that macrophages were common in all 3 subtypes. Finally, we described subtype-specific gene signatures and immune cell composition correlated with phenotypes. These findings reveal the specific epithelial differentiation in normal central facial skin, and epithelial-immune crosstalk in lesions providing insight into an initial keratinocyte pattern in the pathogenesis of rosacea. PMID:34290700 | PMC:PMC8287635 | DOI:10.3389/fimmu.2021.674871 {url} = URL to article
    • Med Res Rev. 2021 Jul 21. doi: 10.1002/med.21842. Online ahead of print. ABSTRACT The sesquiterpene lactone artemisinin from Artemisia annua L. is well established for malaria therapy, but its bioactivity spectrum is much broader. In this review, we give a comprehensive and timely overview of the literature regarding the immunosuppressive activity of artemisinin-type compounds toward inflammatory and autoimmune diseases. Numerous receptor-coupled signaling pathways are inhibited by artemisinins, including the receptors for interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), β3-integrin, or RANKL, toll-like receptors and growth factor receptors. Among the receptor-coupled signal transducers are extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), AKT serine/threonine kinase (AKT), mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK) kinase (MEK), phospholipase C γ1 (PLCγ), and others. All these receptors and signal transduction molecules are known to contribute to the inhibition of the transcription factor nuclear factor κ B (NF-κB). Artemisinins may inhibit NF-κB by silencing these upstream pathways and/or by direct binding to NF-κB. Numerous NF-κB-regulated downstream genes are downregulated by artemisinin and its derivatives, for example, cytokines, chemokines, and immune receptors, which regulate immune cell differentiation, apoptosis genes, proliferation-regulating genes, signal transducers, and genes involved in antioxidant stress response. In addition to the prominent role of NF-κB, other transcription factors are also inhibited by artemisinins (mammalian target of rapamycin [mTOR], activating protein 1 [AP1]/FBJ murine osteosarcoma viral oncogene homologue [FOS]/JUN oncogenic transcription factor [JUN]), hypoxia-induced factor 1α (HIF-1α), nuclear factor of activated T cells c1 (NF-ATC1), Signal transducers and activators of transcription (STAT), NF E2-related factor-2 (NRF-2), retinoic-acid-receptor-related orphan nuclear receptor γ (ROR-γt), and forkhead box P-3 (FOXP-3). Many in vivo experiments in disease-relevant animal models demonstrate therapeutic efficacy of artemisinin-type drugs against rheumatic diseases (rheumatoid arthritis, osteoarthritis, lupus erythematosus, arthrosis, and gout), lung diseases (asthma, acute lung injury, and pulmonary fibrosis), neurological diseases (autoimmune encephalitis, Alzheimer's disease, and myasthenia gravis), skin diseases (dermatitis, rosacea, and psoriasis), inflammatory bowel disease, and other inflammatory and autoimmune diseases. Randomized clinical trials should be conducted in the future to translate the plethora of preclinical results into clinical practice. PMID:34288018 | DOI:10.1002/med.21842 {url} = URL to article
    • An Bras Dermatol. 2021 Jul 15:S0365-0596(21)00173-2. doi: 10.1016/j.abd.2021.02.004. Online ahead of print. ABSTRACT BACKGROUND: The frequency of autoimmune diseases and thyroid cancer has been increasingly reported in association with rosacea. However, studies investigating thyroid diseases in rosacea are scarce with conflicting results. OBJECTIVE: To investigate the relationship between thyroid disorders and rosacea. METHODS: A large case-control study on age- and gender-matched 2091 rosacea patients and 9572 controls was conducted. Rosacea patients using the rosacea-specific ICD codes were compiled from the hospital records. Additionally, all participants were evaluated in terms of the presence of hypothyroidism and hyperthyroidism. Conditional logistic regression analysis was used to compute case-control odds ratios (OR) with 95% confidence intervals. RESULTS: The analysis comprehended 2091 rosacea patients (1546 female, 545 male; mean 48.73 ± 14.53 years) and 9572 controls (7009 female, 2563 male; mean 48.73 ± 15.1 years). Whereas the rate of hypothyroidism was significantly higher in rosacea patients (OR = 1.3, 95% CI 1.13-1.49, p < 0.001), there was no significant difference in the rate of hyperthyroidism between the groups (OR = 1.12, 95% CI 0.81-1.53, p = 0.497). Stratification for genderrevealed a significant association between hypothyroidism and rosacea in females (OR = 1.27, 95% CI 1.1-1.47, p = 0.002) and males (OR = 1.58, 95% CI 1.04-2.4, p = 0.032). The frequency of hypothyroidism in rosacea patients increased towards the age range of 40-49 and then decreased, parallel with the hypothyroidism frequency of the study population. STUDY LIMITATIONS: Different subtypes and severities of rosacea were not distinguished. CONCLUSIONS: Hypothyroidism may be a comorbidity of rosacea and investigation for hypothyroidism may be appropriate when evaluating rosacea patients. PMID:34275693 | DOI:10.1016/j.abd.2021.02.004 {url} = URL to article
    • Clin Cosmet Investig Dermatol. 2021 Jul 6;14:779-814. doi: 10.2147/CCID.S315711. eCollection 2021. ABSTRACT Dermal filler treatments require constant reassessment for improving and safeguarding the rapidly evolving aesthetic field. Suboptimal injection technique, patient selection and product knowledge have touted a concerning increase in filler complications, with new challenges such as the COVID-19 pandemic leading to new paradigms in the understanding, prevention, diagnosis and treatment of complications. The updated 10-point plan has been developed to curtail complications through consideration of causative factors, categorized as patient, product, and procedure-related. Patient-related factors include a preprocedural consultation with careful elucidation of skin conditions (acne, rosacea, dermatitis), systemic disease (allergies, autoimmune disease, underlying bacterial and viral disease (herpes simplex virus, COVID-19 infection), medications (antineoplastic drugs, recreational drugs) and previous cosmetic procedures (including fillers and energy-based devices). Patient assessment should include standardized photography and also evaluate the role of social media, ethnicity, gender, generational, and LGBTQ+ needs. Specified informed consent for both adverse events and their treatment is essential due to the increase in vascular complications, including the risk of blindness. Product-related factors include the powerful advantage of reversibility when using hyaluronic acid (HA) products. Product characteristics such as molecular weight and filler degradation should be understood. Product layering over late or minimally degradable fillers is still inadvisable due to the initial filler being teased into reactivity. Procedural factors such as consistent photographic documentation, procedural planning, aseptic non-touch technique (ANTT), knowledge of topographical anatomy and angiosomes, and technical dexterity including pinch anatomy and needle skills are of pivotal importance. The final section is dedicated to algorithms and checklists for managing and treating complications such as allergic hypersensitivity reactions, vascular events, infection, edema and late-onset adverse events (LOAEs). The updated 10-point plan is a methodical strategy aimed at further minimising the risk of dermal filler complications. PMID:34276222 | PMC:PMC8279269 | DOI:10.2147/CCID.S315711 {url} = URL to article
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