High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-trafficking property.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease with a Th17-skewed immune phenotype. Although it has been generally accepted that regulatory T cells (Tregs) in lesional psoriatic skin have functional impairment due to the local inflammatory microenvironment, the molecular properties of skin-homing psoriatic Tregs have not been well explored. METHODS: We designed an extensive 39 marker mass cytometry (CyTOF) panel to deeply profile the immune landscape of skin-homing Tregs from 31 people with psoriasis stratified by psoriasis area severity index score as mild (n = 15) to moderate-severe (n = 16) and 32 healthy controls. We further validated the findings with an in-vitro chemokine-mediated Treg migration assay, immunofluorescent imaging of normal and psoriatic lesional skin and analysed public single-cell RNA-sequencing datasets to expand upon our findings into the local tissue microenvironments. FINDINGS: We discovered an overall decrease in CLAhi Tregs and specifically, CLAhiCCR5+ Tregs in psoriasis. Functional markers CD39 and FoxP3 were elevated in psoriatic Tregs. However, CCR7 expression was significantly increased while CCR4 and CLA expression was reduced in psoriatic Tregs and CLAhi Tregs, which was associated with disease severity. Moreover, psoriatic Tregs revealed increased migratory capacity towards CCR7's ligands, CCL19/CCL21. Interrogation of public single-cell RNA sequencing data confirmed reduced expression of skin-trafficking markers in lesional-skin Tregs compared to non-lesioned skin, further substantiated by immunofluorescent staining. INTERPRETATION: Psoriatic circulating Tregs showed an impaired skin-trafficking phenotype thus leading to insufficient suppression of ongoing inflammation in the lesional skin, expanding upon our current understanding of the impairment of Treg-mediated immunosuppression in psoriasis. FUNDING: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and Information and Communications Technology (2020R1C1C1014513, 2021R1A4A5032185, 2020R1F1A1073692); and the new faculty research seed money grant of Yonsei University College of Medicine for 2021 (2021-32-0033).

Comparing the diagnostic accuracy of PCR-reverse blot hybridization assay and conventional fungus study in superficial fungal infection of the skin: A systematic review.

BACKGROUND: In superficial fungal infections, prompt diagnosis and treatment are essential to prevent the spread of infection and minimise the impact on patients' quality of life. Traditional diagnostic methods, such as KOH smear and fungal culture, have limitations in terms of sensitivity and turnaround time. Recently, the PCR-reverse blot hybridization assay (PCR-REBA) has been developed for the direct detection of dermatophyte DNA. However, there is a lack of information assessing the diagnostic accuracy of PCR-REBA. OBJECTIVES: This systematic review aimed to evaluate the diagnostic accuracy of PCR-REBA in superficial fungal infections compared to conventional and molecular methods. METHODS: The comprehensive search containing Ovid MEDLINE and Embase databases was conducted on 7 August 2022. Two reviewers independently reviewed the included articles. Quality assessment was performed using the Newcastle-Ottawa Scale tool. RESULTS: The included studies were conducted in Korea (five studies) and the Netherlands (two studies), all of which were conducted in a single institution. The quality assessment of these studies indicated low risk of bias. When compared to the potassium hydroxide (KOH) smear and fungus culture, the sensitivity of PCR-REBA ranged from 85% to 100%, and the positive predictive values ranged from 58.9% to 100%. When compared to the RT-PCR, the sensitivity of PCR-REBA ranged from 93.3% to 100%, and the positive and negative predictive values were 91.6%-99.6% and 81.0%-89.1%, respectively. CONCLUSIONS: The PCR-REBA shows promise as a valuable diagnostic tool for dermatophytosis, offering practical and cost-effective benefits.

Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19.

Importance: Multiple cases of autoimmune and autoinflammatory diseases after COVID-19 have been reported. However, their incidences and risks have rarely been quantified. Objective: To investigate the incidences and risks of autoimmune and autoinflammatory connective tissue disorders after COVID-19. Design, Setting, and Participants: This was a retrospective population-based study conducted between October 8, 2020, and December 31, 2021, that used nationwide data from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort and included individuals who received a diagnosis of COVID-19 via polymerase chain reaction testing and a control group with no evidence of COVID-19 identified from National Health Insurance Service of Korea cohort. Data analysis was conducted from September 2022 to August 2023. Exposures: Receipt of diagnosis of COVID-19. Main Outcomes and Measures: The primary outcomes were the incidence and risk of autoimmune and autoinflammatory connective tissue disorders following COVID-19. A total of 32 covariates, including demographics, socioeconomic statuses, lifestyle factors, and comorbidity profiles, were balanced through inverse probability weighting. The incidences and risks of autoimmune and autoinflammatory connective tissue disorders were compared between the groups using multivariable Cox proportional hazard analyses. Results: A total of 354 527 individuals with COVID-19 (mean [SD] age, 52.24 [15.55] years; 179 041 women [50.50%]) and 6 134 940 controls (mean [SD] age, 52.05 [15.63] years; 3 074 573 women [50.12%]) were included. The risks of alopecia areata (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.05-1.19), alopecia totalis (aHR, 1.74; 95% CI, 1.39-2.17), antineutrophil cytoplasmic antibody-associated vasculitis (aHR, 2.76; 95% CI, 1.64-4.65), Crohn disease (aHR, 1.68; 95% CI, 1.31-2.15), and sarcoidosis (aHR, 1.59; 95% CI, 1.00-2.52) were higher in the COVID-19 group. The risks of alopecia totalis, psoriasis, vitiligo, vasculitis, Crohn disease, ulcerative colitis, rheumatoid arthritis, adult-onset Still disease, Sjögren syndrome, ankylosing spondylitis, and sarcoidosis were associated with the severity of COVID-19. Conclusions and Relevance: In this retrospective cohort study, COVID-19 was associated with a substantial risk for autoimmune and autoinflammatory connective tissue disorders, indicating that long-term management of patients with COVID-19 should include evaluation for such disorders.

Prevalence and incidence of comorbid diseases and mortality risk associated with lichen planopilaris: a Korean nationwide population-based study.

BACKGROUND: Various comorbid diseases have been reported in patients with lichen planopilaris (LPP); however, data regarding the risks of incident diseases and mortality are lacking. OBJECTIVES: To investigate the risks of incident diseases and mortality associated with LPP. METHODS: This was a retrospective nationwide population-based study, using data from the National Health Insurance Service Database of Korea from 2002 to 2019. Patients aged ≥ 18 years with three or more documented medical visits for LPP were included. The adjusted hazard ratios (aHRs) for incident disease outcomes and mortality were compared with 1 : 20 age-, sex-, insurance type- and income-level-matched controls. RESULTS: In total, 2026 patients with LPP and 40 520 controls were analysed. The risks of incident systemic lupus erythematosus [aHR 1.91, 95% confidence interval (CI) 1.21-3.03], psoriasis (aHR 3.42, 95% CI 2.83-4.14), rheumatoid arthritis (aHR 1.39, 95% CI 1.19-1.63), lichen planus (aHR, 10.07, 95% CI 7.17-14.15), atopic dermatitis (aHR 2.15, 95% CI 1.90-2.44), allergic rhinitis (aHR 1.29, 95% CI 1.13-1.49), thyroid diseases (hyperthyroidism: aHR 1.42, 95% CI 1.14-1.77, hypothyroidism aHR 1.19 95% CI 1.01-1.41, and thyroiditis: aHR, 1.35, 95% CI 1.08-1.69), nonmelanoma skin cancer (aHR 2.33, 95% CI 1.00-5.44) and vitamin D deficiency (aHR 1.23, 95% CI 1.03-1.47) were higher in patients with LPP. Patients with LPP had a higher mortality rate than controls (aHR 1.30, 95% CI 1.04-1.61), although the risk was not significant after adjusting for comorbidities (aHR 1.08, 95% CI 0.87-1.34). CONCLUSIONS: Patients with LPP had a higher risk of various diseases following LPP diagnosis. Close follow-up is needed to optimize comprehensive patient care.

Hyperglycemia-activated 11ß-hydroxysteroid dehydrogenase type 1 increases endoplasmic reticulum stress and skin barrier dysfunction.

The diabetes mellitus (DM) skin shows skin barrier dysfunction and skin lipid abnormality, similar to conditions induced by systemic or local glucocorticoid excess and aged skin. Inactive glucocorticoid (GC) is converted into active glucocorticoid by 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). Hyperglycemia in DM and excessive GC are known to increase endoplasmic reticulum (ER) stress. We hypothesized that hyperglycemia affects systemic GC homeostasis and that the action of skin 11ß-HSD1 and GC contributes to increased ER stress and barrier defects in DM. We compared 11ß-HSD1, active GC, and ER stress between hyperglycemic and normoglycemic conditions in normal human keratinocytes and db/db mice. 11ß-HSD1 and cortisol increased with time in keratinocyte culture under hyperglycemic conditions. 11ß-HSD1 siRNA-transfected cells did not induce cortisol elevation in hyperglycemic condition. The production of 11ß-HSD1 and cortisol was suppressed in cell culture treated with an ER stress-inhibitor. The 14-week-old db/db mice showed higher stratum corneum (SC) corticosterone, and skin 11ß-HSD1 levels than 8-week-old db/db mice. Topical 11ß-HSD1 inhibitor application in db/db mice decreased SC corticosterone levels and improved skin barrier function. Hyperglycemia in DM may affect systemic GC homeostasis, activate skin 11ß-HSD1, and induce local GC excess, which increases ER stress and adversely affects skin barrier function.

All-Cause and Cause-Specific Mortality Risks among Patients with Hidradenitis Suppurativa: A Korean Nationwide Population-Based Cohort Study.

Although previous studies have reported increased mortality in patients with hidradenitis suppurativa (HS), the cause-specific mortality and the clinical characteristics attributable to greater mortality remain unclear. The aim of this study was to investigate all-cause and cause-specific mortality risks associated with HS. A retrospective population-based cohort study using the data linkage of the Nationwide Health Insurance Service database and the National Death Registry of Korea was conducted. Patients were defined as individuals with ≥3 documented visits with HS from 2003 to 2019. Controls were matched at a 1:10 ratio with age, sex, insurance type, and income level. The study included 26,304 patients with HS and 263,040 controls. Patients with HS showed a higher risk of all-cause mortality (hazard ratio = 1.152, 95% confidence interval = 1.051-1.263) than controls. However, the difference was comparable after further adjustment for body mass index, smoking, drinking, and comorbidity (adjusted hazard ratio = 1.038, 95% confidence interval = 0.946-1.138). For cause-specific mortality, the mortality from suicide/psychiatric disease (adjusted hazard ratio = 1.449, 95% confidence interval = 1.098-2.911) and renal/urogenital disease (adjusted hazard ratio = 1.801, 95% confidence interval = 1.080-3.004) were independently higher among patients with HS even after adjustment for the confounding factors.

Morphologic and molecular biologic analyses of the skin rejuvenation effect of the fractional 1064-nm picosecond laser: An animal study.

OBJECTIVES: Application of the picosecond laser in the field of dermatology has expanded from tattoo removal to skin rejuvenation on a clinical basis. Although various mechanisms of pigment removal have been elucidated, the molecular changes associated with skin rejuvenation have yet to be identified. The aim of this study was to explore the theoretical basis and to evaluate the efficacy of skin rejuvenation using a 1064-nm fractional picosecond laser in a mouse model. METHODS: We conducted an in vivo study using a fractional picosecond laser on the skin of old and young female hairless mice and performed topographical, histological, micro-, and electron microscopic assessments. RESULTS: The topography of the skin surface was enhanced and showed increased dermal thickness on histological examination. Electron microscopy revealed disarranged collagen bundles with microspaces and vascular leakage in the upper dermis. Levels of collagen synthesis markers and various inflammatory cytokines, such as procollagens, interleukin-1ß, tumor necrosis factor-α, and heat shock proteins, were elevated in the laser-treated skin. CONCLUSIONS: This study provides a possible mechanism for the skin rejuvenation effect of fractional picosecond laser that has been reported previously in clinical observations. Based on our findings, the fractional picosecond laser could be widely applied in clinical settings where dermal regeneration and promotion of skin rejuvenation is required.

Comparison of the Efficacy and Safety of Biologics (Secukinumab, Ustekinumab, and Guselkumab) for the Treatment of Moderate-to-Severe Psoriasis: Real-World Data from a Single Korean Center.

Biologics are important treatment options for psoriasis; however, direct comparison of their efficacy, safety, and drug survival is insufficient in clinical practice. This retrospective single-center study aimed to compare the efficacy, safety, and drug survival of three commonly used psoriasis biologics (secukinumab, ustekinumab, and guselkumab) and identify the factors affecting drug survival in actual clinics in Korea. We enrolled 111 patients with moderate to severe psoriasis and for at least 56 weeks of follow-up; among these, 27, 23, and 61 were administered secukinumab, ustekinumab, and guselkumab, respectively. All groups were comparable with respect to their baseline characteristics. Secukinumab showed a rapid response, and guselkumab was superior in terms of a long-term response and complete remission compared with other biologics, while ustekinumab showed a lower efficacy compared with other biologics. All three biologics had a favorable and similar safety profile; however, allergic reactions and latent tuberculosis were more common with secukinumab and ustekinumab, respectively. Guselkumab was the most sustained biologic, and the survival rates of secukinumab and ustekinumab were similar. Drug survival was remarkably shorter in female patients and those with hypertension. Introduction of new biologics emerged as a negative factor for drug survival in clinical settings.

Relationship of Hair Regrowth Pattern in Alopecia Areata Patches According to DIMT Classification with Treatment Modalities and Patch Size: A Retrospective Cross-Sectional Analysis.

BACKGROUND: The morphology of hair regrowth in alopecia areata (AA) patches could be classified into four types, namely diffuse, irregular, marginal, and targetoid patterns, according to the DIMT classification. However, factors affecting hair regrowth patterns have not been investigated. OBJECTIVE: We investigated whether the DIMT-classified hair regrowth patterns of AA patches are associated with treatment modality and patch size. METHODS: We conducted a retrospective, cross-sectional study of 152 AA patches with hair regrowth. RESULTS: The associations between the diffuse pattern and patch size >2 cm (p=0.006; odds ratio [OR]: 0.36, 95% confidence interval [CI]: 0.17~0.74), between the irregular pattern and triamcinolone acetonide intralesional injection (p<0.001; OR: 274.87, 95% CI: 25.75~2,933.56), between the marginal pattern and systemic and topical corticosteroid (p=0.018; OR: 4.89, 95% CI: 1.31~18.27), and between the targetoid pattern and patch size >2 cm (p=0.028; OR: 2.50, 95% CI: 1.10~5.68) were statistically significant. CONCLUSION: Treatment modalities and patch size are the factors affecting hair regrowth patterns in AA patches.

Increased prevalence of transfusion-transmitted diseases among people with tattoos: A systematic review and meta-analysis.

Whether having a tattoo increases the risk of transfusion-transmitted diseases (TTDs) is controversial. Although a few studies have suggested a strong association between having tattoos and TTDs, other studies have not shown the significance of the association. In addition, previous studies mainly focused only on hepatitis C viral infections. The objective of our study was to identify the prevalence and risk of TTDs in people with tattoos as compared with the non-tattooed population. A systematic review of the studies published before January 22, 2021, was performed using the Pubmed, Embase, and Web of Science databases. Observational studies on hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), and syphilis infections in people with and without tattoos were included. Studies that reported disease status without serological confirmation were excluded. A total of 121 studies were quantitatively analyzed. HCV (odds ratio [OR], 2.37; 95% confidence interval [CI], 2.04-2.76), HBV (OR, 1.55; 95% CI, 1.31-1.83), and HIV infections (OR, 3.55; 95% CI, 2.34-5.39) were more prevalent in the tattooed population. In subgroup analyses, the prevalence of HCV infection was significantly elevated in the general population, hospital patient, blood donor, intravenous (IV) drug user, and prisoner groups. IV drug users and prisoners showed high prevalence rates of HBV infection. The prevalence of HIV infection was significantly increased in the general population and prisoner groups. Having a tattoo is associated with an increased prevalence of TTDs. Our approach clarifies in-depth and supports a guideline for TTD screening in the tattooed population.

A Lipid Mixture Enriched by Ceramide NP with Fatty Acids of Diverse Chain Lengths Contributes to Restore the Skin Barrier Function Impaired by Topical Corticosteroid.

INTRODUCTION: The stratum corneum (SC) is a skin barrier that consists of corneocytes, intercellular lipids, and corneodesmosomes. Ceramides are composed of sphingoid bases linked with various types of fatty acids (FAs), and they are an essential constituent of SC intercellular lipids. Among their subtypes, ceramide NP with a phytosphingosine base is especially important. Most of the previous studies on barrier recovery have focused on a specific ceramide with a single chain FA, not with diverse chain lengths. Skin barrier function is impaired by various factors, including topical corticosteroid. OBJECTIVE: We evaluated whether a lipid mixture enriched by ceramide NP with FAs of diverse chain lengths (CER [NP]*) can restore the skin barrier function impaired by topical corticosteroid. METHODS: Twenty-seven healthy adult male volunteers were recruited. Topical corticosteroid was applied on both volar forearms of volunteers. Then, the test cream containing a lipid mixture with CER (NP)* was applied on the left forearm, and a vehicle cream without a lipid mixture was applied on the right forearm of each subject. The functional parameters of the skin barrier were compared before and after the treatment. Epidermal differentiation markers, hyaluronic acid synthase 3 (HAS3), cytokine levels, and the lipid profiles in the SC were analyzed. RESULTS: The functional parameters of the skin barrier, such as barrier recovery rate, SC integrity, and SC hydration were significantly improved in the test cream-applied site compared to the vehicle cream-applied sites. Filaggrin and HAS3 levels were significantly higher in the sites applied with the test cream. Interleukin (IL)-1α levels were also significantly increased in these sites. IL-2, IL-6, IL-10, and IL-13 levels were significantly decreased in the test cream-applied sites. Lipid analyses showed that C18, C20, and total ceramide NP levels significantly increased in the sites where the test cream was applied. Also, C16, C18, C20, C24, and total ceramide NP levels were significantly elevated in the test cream-applied sites after acute barrier disruption. CONCLUSION: Our results demonstrate that a lipid mixture enriched by CER (NP)* could recover the barrier function impaired by topical corticosteroid.