A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils.

Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here, we examined the roles of dermal cDC1s and cDC2s during bacterial infection, notably Propionibacterium acnes (P. acnes). cDC1s, but not cDC2s, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. Single-cell mRNA sequencing revealed that this regulation relied on secretion of the cytokine vascular endothelial growth factor α (VEGF-α) by a minor subset of activated EpCAM+CD59+Ly-6D+ cDC1s. Neutrophil recruitment by dermal cDC1s was also observed during S. aureus, bacillus Calmette-Guérin (BCG), or E. coli infection, as well as in a model of bacterial insult in human skin. Thus, skin cDC1s are essential regulators of the innate response in cutaneous immunity and have roles beyond classical antigen presentation.

Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo.

BACKGROUND: Vitiligo is a chronic autoimmune disease that causes skin depigmentation. A cream formulation of ruxolitinib (an inhibitor of Janus kinase 1 and 2) resulted in repigmentation in a phase 2 trial involving adults with vitiligo. METHODS: We conducted two phase 3, double-blind, vehicle-controlled trials (Topical Ruxolitinib Evaluation in Vitiligo Study 1 [TRuE-V1] and 2 [TRuE-V2]) in North America and Europe that involved patients 12 years of age or older who had nonsegmental vitiligo with depigmentation covering 10% or less of total body-surface area. Patients were randomly assigned in a 2:1 ratio to apply 1.5% ruxolitinib cream or vehicle control twice daily for 24 weeks to all vitiligo areas on the face and body, after which all patients could apply 1.5% ruxolitinib cream through week 52. The primary end point was a decrease (improvement) of at least 75% from baseline in the facial Vitiligo Area Scoring Index (F-VASI; range, 0 to 3, with higher scores indicating a greater area of facial depigmentation), or F-VASI75 response, at week 24. There were five key secondary end points, including improved responses on the Vitiligo Noticeability Scale. RESULTS: A total of 674 patients were enrolled, 330 in TRuE-V1 and 344 in TRuE-V2. In TRuE-V1, the percentage of patients with an F-VASI75 response at week 24 was 29.8% in the ruxolitinib-cream group and 7.4% in the vehicle group (relative risk, 4.0; 95% confidence interval [CI], 1.9 to 8.4; P<0.001). In TRuE-V2, the percentages were 30.9% and 11.4%, respectively (relative risk, 2.7; 95% CI, 1.5 to 4.9; P<0.001). The results for key secondary end points showed superiority of ruxolitinib cream over vehicle control. Among patients who applied ruxolitinib cream throughout 52 weeks, adverse events occurred in 54.8% in TRuE-V1 and 62.3% in TRuE-V2; the most common adverse events were application-site acne (6.3% and 6.6%, respectively), nasopharyngitis (5.4% and 6.1%), and application-site pruritus (5.4% and 5.3%). CONCLUSIONS: In two phase 3 trials, application of ruxolitinib cream resulted in greater repigmentation of vitiligo lesions than vehicle control through 52 weeks, but it was associated with acne and pruritus at the application site. Larger and longer trials are required to determine the effect and safety of ruxolitinib cream in patients with vitiligo. (Funded by Incyte; TRuE-V1 and TRuE-V2 ClinicalTrials.gov numbers, NCT04052425 and NCT04057573.).

Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism.

Acne vulgaris is a chronic disfiguring skin disease affecting ∼1 billion people worldwide, often having persistent negative effects on physical and mental health. The Gram-positive anaerobe, Cutibacterium acnes is implicated in acne pathogenesis and is, therefore, a main target for antibiotic-based acne therapy. We determined a 2.8-Šresolution structure of the 70S ribosome of Cutibacterium acnes by cryogenic electron microscopy and discovered that sarecycline, a narrow-spectrum antibiotic against Cutibacterium acnes, may inhibit two active sites of this bacterium's ribosome in contrast to the one site detected previously on the model ribosome of Thermus thermophilus. Apart from the canonical binding site at the mRNA decoding center, the second binding site for sarecycline exists at the nascent peptide exit tunnel, reminiscent of the macrolides class of antibiotics. The structure also revealed Cutibacterium acnes-specific features of the ribosomal RNA and proteins. Unlike the ribosome of the Gram-negative bacterium Escherichia coli, Cutibacterium acnes ribosome has two additional proteins, bS22 and bL37, which are also present in the ribosomes of Mycobacterium smegmatis and Mycobacterium tuberculosis. We show that bS22 and bL37 have antimicrobial properties and may be involved in maintaining the healthy homeostasis of the human skin microbiome.

Rhizoma Paridis saponins attenuate Gram-negative bacteria-induced inflammatory acne by binding to KEAP1 and modulating Nrf2 and MAPK pathways.

Acne vulgaris represents a chronic inflammatory condition, the pathogenesis of which is closely associated with the altered skin microbiome. Recent studies have implicated a profound role of Gram-negative bacteria in acne development, but there is a lack of antiacne agents targeting these bacteria. Polyphyllins are major components of Rhizoma Paridis with great anti-inflammatory potential. In this study, we aimed to evaluate the antiacne effects and the underlying mechanisms of PPH and a PPH-enriched Rhizoma Paridis extract (RPE) in treating the Gram-negative bacteria-induced acne. PPH and RPE treatments significantly suppressed the mRNA and protein expressions of interleukin (IL)-1ß and IL-6 in lipopolysaccharide (LPS)-induced RAW 264.7 and HaCaT cells, along with the intracellular reactive oxygen species (ROS) generation. Furthermore, PPH and RPE inhibited the nuclear translocation of nuclear factor kappa-B (NF-κB) P65 in LPS-induced RAW 264.7 cells. Based on molecular docking, PPH could bind to kelch-like ECH-associated protein 1 (KEAP1) protein. PPH and RPE treatments could activate nuclear factor erythroid 2-related factor 2 (NRF2) and upregulate haem oxygenase-1 (HO-1). Moreover, RPE suppressed the mitogen-activated protein kinase (MAPK) pathway. Therefore, PPH-enriched RPE showed anti-inflammatory and antioxidative effects in vitro, which is promising for alternative antiacne therapeutic.

Haplotype analysis and linkage disequilibrium of ApoB gene polymorphisms and its relationship with hyperlipidemia in patients with acne vulgaris.

BACKGROUND: Acne vulgaris (AV) is a chronic, multifactorial inflammatory disease of the pilosebaceous unit brought on by hormonal imbalance, excessive sebum production, follicular hyperkeratinization, inflammation and Cutibacterium acne. Acne patients are characterized by alteration of the lipid profile. Apolipoprotein B gene (ApoB) plays an essential role in lipoprotein biosynthesis and multiple single-nucleotide polymorphisms (SNPs) in ApoB are associated with dyslipidemia. AIM: The aim of this study was to estimate the alteration of lipid profiles in AV, determine the genetic association with lipid profile alteration by studying the ApoB gene polymorphisms, and to identify the exact haplotypes associated with acne and lipid profile alteration. SUBJECTS AND METHODS: In a case-control study consisting of 63 non-obese acne patients and 43 healthy controls, all participants underwent biochemical, anthropological assessments, and genetic analysis for ApoB polymorphisms. RESULT: Our results indicate that serum ApoB and the lipid profile were higher in acne patients compared with healthy subject. The most common haplotypes in acne patients were rs562338 A/rs17240441 I/c.12669 A/rs1042034 G, whereas the most common haplotypes in healthy subjects were rs562338 G/rs17240441 D/c.12669 A/rs1042034 G. Patients with mild acne had higher serum ApoB levels p = 0.005. Also, the low-density lipoprotein cholesterol (LDL-C) level was higher in mild acne compared with other acne groups, with a highly significant variation of p ≤ 0.001. CONCLUSION: We found a significant variation between the acne group and healthy controls in serum ApoB, triglycerides, total cholesterol and LDL-C. The most common haplotypes in acne patients are rs562338 A/, rs17240441 I/, c.12669 A/ and rs1042034 G, and there is a linkage disequilibrium between the four selected SNPs.

Interrupting an IFN-γ-dependent feedback loop in the syndrome of pyogenic arthritis with pyoderma gangrenosum and acne.

OBJECTIVES: To study the molecular pathogenesis of PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome, a debilitating hereditary autoinflammatory disease caused by dominant mutation in PSTPIP1. METHODS: Gene knock-out and knock-in mice were generated to develop an animal model. THP1 and retrovirally transduced U937 human myeloid leukaemia cell lines, peripheral blood mononuclear cells, small interfering RNA (siRNA) knock-down, site-directed mutagenesis, cytokine immunoassays, coimmunoprecipitation and immunoblotting were used to study inflammasome activation. Cytokine levels in the skin were evaluated by immunohistochemistry. Responsiveness to Janus kinase (JAK) inhibitors was evaluated ex vivo with peripheral blood mononuclear cells and in vivo in five treatment-refractory PAPA patients. RESULTS: The knock-in mouse model of PAPA did not recapitulate the human disease. In a human myeloid cell line model, PAPA-associated PSTPIP1 mutations activated the pyrin inflammasome, but not the NLRP3, NLRC4 or AIM2 inflammasomes. Pyrin inflammasome activation was independent of the canonical pathway of pyrin serine dephosphorylation and was blocked by the p.W232A PSTPIP1 mutation, which disrupts pyrin-PSTPIP1 interaction. IFN-γ priming of monocytes from PAPA patients led to IL-18 release in a pyrin-dependent manner. IFN-γ was abundant in the inflamed dermis of PAPA patients, but not patients with idiopathic pyoderma gangrenosum. Ex vivo JAK inhibitor treatment attenuated IFN-γ-mediated pyrin induction and IL-18 release. In 5/5 PAPA patients, the addition of JAK inhibitor therapy to IL-1 inhibition was associated with clinical improvement. CONCLUSION: PAPA-associated PSTPIP1 mutations trigger a pyrin-IL-18-IFN-γ positive feedback loop that drives PAPA disease activity and is a target for JAK inhibition.

Very low-calorie ketogenic diet (VLCKD): a therapeutic nutritional tool for acne?

BACKGROUND: Acne, a chronic inflammatory disease impacting the pilosebaceous unit, is influenced significantly by inflammation and oxidative stress, and is commonly associated with obesity. Similarly, obesity is also associated with increased inflammation and oxidation. The role of diet in acne remains inconclusive, but the very low-calorie ketogenic diet (VLCKD), known for weight loss and generating anti-inflammatory ketone bodies, presents promising potential. Despite this, the effects of VLCKD on acne remain underexplored. This study aimed to investigate the efficacy of a 45-day active phase of VLCKD in reducing the clinical severity of acne in young women with treatment-naïve moderate acne and grade I obesity. METHODS: Thirty-one women with treatment-naïve moderate acne, grade I obesity (BMI 30.03-34.65 kg/m2), aged 18-30 years, meeting inclusion/exclusion criteria, and consenting to adhere to VLCKD were recruited. Baseline and post-intervention assessments included anthropometric measurements, body composition, phase angle (PhA), trimethylamine N-oxide (TMAO) levels, and reactive oxygen metabolite derivatives (dROMs) as markers of inflammation, dysbiosis, and oxidative stress, respectively. A comprehensive dermatological examination, incorporating the Global Acne Grading System (GAGS) and the Dermatology Life Quality Index (DLQI), was conducted for all women. RESULTS: VLCKD resulted in general improvements in anthropometric and body composition parameters. Significantly, there were significant reductions in both the GAGS score (Δ%: - 31.46 ± 9.53, p < 0.001) and the DLQI score (Δ%: - 45.44 ± 24.02, p < 0.001) after the intervention. These improvements coincided with significant decreases in TMAO (p < 0.001) and dROMs (p < 0.001) levels and a significant increase in PhA (Δ%: + 8.60 ± 7.40, p < 0.001). Changes in the GAGS score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjusting for Δ% FM. Changes in the DLQI score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjustment for Δ% FM. CONCLUSION: Given the side effects of drugs used for acne, there is an increasing need for safe, tolerable, and low-cost treatments that can be used for acne disease. The 45-day active phase of VLCKD demonstrated notable improvements in acne severity, and these improvements seemed to be attributable to the known antioxidant and anti-inflammatory effects of VLCKD.

Engineering selectivity of Cutibacterium acnes phages by epigenetic imprinting.

Cutibacterium acnes (C. acnes) is a gram-positive bacterium and a member of the human skin microbiome. Despite being the most abundant skin commensal, certain members have been associated with common inflammatory disorders such as acne vulgaris. The availability of the complete genome sequences from various C. acnes clades have enabled the identification of putative methyltransferases, some of them potentially belonging to restriction-modification (R-M) systems which protect the host of invading DNA. However, little is known on whether these systems are functional in the different C. acnes strains. To investigate the activity of these putative R-M and their relevance in host protective mechanisms, we analyzed the methylome of six representative C. acnes strains by Oxford Nanopore Technologies (ONT) sequencing. We detected the presence of a 6-methyladenine modification at a defined DNA consensus sequence in strain KPA171202 and recombinant expression of this R-M system confirmed its methylation activity. Additionally, a R-M knockout mutant verified the loss of methylation properties of the strain. We studied the potential of one C. acnes bacteriophage (PAD20) in killing various C. acnes strains and linked an increase in its specificity to phage DNA methylation acquired upon infection of a methylation competent strain. We demonstrate a therapeutic application of this mechanism where phages propagated in R-M deficient strains selectively kill R-M deficient acne-prone clades while probiotic ones remain resistant to phage infection.

Antibacterial activity and mechanism of cell-free supernatants of Lacticaseibacillus paracasei against Propionibacterium acnes.

Propionibacterium acnes (P. acnes) is an anaerobic and gram-positive bacterium involved in the pathogenesis and inflammation of acne vulgaris. This study particularly focuses on the antimicrobial effect of Lacticaseibacillus paracasei LPH01 against P. acnes, a bacterium that causes acne vulgaris. Fifty-seven Lactobacillus strains were tested for their ability to inhibit P. acnes growth employing the Oxford Cup and double dilution methods. The cell-free supernatant (CFS) of L. paracasei LPH01 demonstrated a strong inhibitory effect, with an inhibition zone diameter of 24.65 ± 0.27 mm and a minimum inhibitory concentration of 12.5 mg/mL. Among the CFS, the fraction over 10 kDa (CFS-10) revealed the best antibacterial effect. Confocal laser scanning microscopes and flow cytometry showed that CFS-10 could reduce cell metabolic activity and cell viability and destroy the integrity and permeability of the cell membrane. A scanning electron microscope revealed that bacterial cells exhibited obvious morphological and ultrastructural changes, which further confirmed the damage of CFS-10 to the cell membrane and cell wall. Findings demonstrated that CFS-10 inhibited the conversion of triglycerides, decreased the production of free fatty acids, and down-regulated the extracellular expression of the lipase gene. This study provides a theoretical basis for the metabolite of L. paracasei LPH01 as a potential antibiotic alternative in cosmeceutical skincare products.

Comparative transcriptome analysis of acne vulgaris, rosacea, and hidradenitis suppurativa supports high-dose dietary zinc as a therapeutic agent.

Acne vulgaris, rosacea, and hidradenitis suppurativa are enduring inflammatory skin conditions that frequently manifest with akin clinical attributes, posing a considerable challenge for their distinctive diagnosis. While these conditions do exhibit certain resemblances, they also demonstrate distinct underlying pathophysiological mechanisms and treatment modalities. Delving into both the molecular parallels and disparities among these three disorders can yield invaluable insights for refined diagnostics, effective management, and targeted therapeutic interventions. In this report, we present a comparative analysis of transcriptomic data across these three diseases, elucidating differentially expressed genes and enriched pathways specific to each ailment, as well as those shared among them. Specifically, we identified multiple zinc-binding proteins (SERPINA1, S100A7, S100A8, S100A9 and KRT16) as consistently highly upregulated genes across all three diseases. Our hypothesis suggests that these proteins could bind and sequester zinc, potentially leading to localized zinc deficiency and heightened inflammation. We identified high-dose dietary zinc as a promising therapeutic approach and confirmed its effectiveness through validation in an acne mouse model.

Effect of isotretinoin on CYP2D6 and CYP3A activity in patients with severe acne.

AIMS: Previously, retinoids have decreased CYP2D6 mRNA expression in vitro and induced CYP3A4 in vitro and in vivo. This study aimed to determine whether isotretinoin administration changes CYP2D6 and CYP3A activities in patients with severe acne. METHODS: Thirty-three patients (22 females and 11 males, 23.5 ± 6.0 years old) expected to receive isotretinoin treatment completed the study. All participants were genotyped for CYP2D6 and CYP3A5. Participants received dextromethorphan (DM) 30 mg orally as a dual-probe substrate of CYP2D6 and CYP3A activity at two study timepoints: pre-isotretinoin treatment and with isotretinoin for at least 1 week. The concentrations of isotretinoin, DM and their metabolites were measured in 2-h postdose plasma samples and in cumulative 0-4-h urine collections using liquid chromatography-mass spectrometry. RESULTS: In CYP2D6 extensive metabolizers, the urinary dextrorphan (DX)/DM metabolic ratio (MR) (CYP2D6 activity marker) was numerically, but not significantly, lower with isotretinoin administration compared to pre-isotretinoin (geometric mean ratio [GMR] [90% confidence interval (CI)] 0.78 [0.55, 1.11]). The urinary 3-hydroxymorphinan (3HM)/DX MR (CYP3A activity marker) was increased (GMR 1.18 [1.03, 1.35]) and the urinary DX-O-glucuronide/DX MR (proposed UGT2B marker) was increased (GMR 1.22 [1.06, 1.39]) with isotretinoin administration compared to pre-isotretinoin. CONCLUSIONS: Administration of isotretinoin did not significantly reduce CYP2D6 activity in extensive metabolizers, suggesting that the predicted downregulation of CYP2D6 based on in vitro data does not translate into humans. We observed a modest increase in CYP3A activity (predominantly CYP3A4) with isotretinoin treatment. The data also suggest that DX glucuronidation is increased following isotretinoin administration.

The epidemiology of acne vulgaris in a multiethnic adolescent population from Rotterdam, the Netherlands: A cross-sectional study.

BACKGROUND: Although acne is a prevalent multifactorial inflammatory skin condition, few studies were performed in multiethnic populations. OBJECTIVES: To study the prevalence and determinants of acne in a multiethnic study at the start of puberty. METHODS: This cross-sectional study is embedded in Generation R, a population-based prospective study from Rotterdam, the Netherlands. Three-dimensional facial photos at the center visit in 2016-2019 (of ∼13-year-olds) were used to grade acne severity using the Global Evaluation of the Acne Severity (GEA). Analyses were stratified by biological sex and explored through chi-square tests and multivariable ordinal logistic regression. RESULTS: A total of 4561 children (51% girls) with a median age of 13.5 (IQR 13.3-13.6) were included. The visible acne prevalence (GEA 2-5) for girls vs boys was 62% vs 45% and moderate-to-severe acne (GEA 3-5) 14% vs 9%. Higher puberty stages (adjusted odds ratios: 1.38 [1.20-1.59] and 2.16 [1.86-2.51] for girls and boys, respectively) and darker skin colors V and VI (adjusted odds ratios: 1.90 [1.17-3.08] and 2.43 [1.67-3.56]) were associated with more severe acne in both sexes, and being overweight in boys (adjusted odds ratio: 1.58 [1.15-2.17]). LIMITATIONS: Cross-sectional design. CONCLUSIONS: Acne prevalence was high at the age of 13 years and was associated with advanced puberty, darker skin color, and weight status.

Adult Acne in Middle-age: Effects on Mental Health in General Population of the Northern Finland Birth Cohort 1966.

The impact of adult acne on patients' mental health has not been widely studied, and most studies have been conducted within specific patient populations. The current study examines the association between adult acne and psychological symptoms in the Northern Finland Birth Cohort 1966 (NFBC1966) (n = 1,907). The cohort members attended a health study at the age of 46 years, which comprised a whole-body examination performed by dermatologists to identify acne, and answering the Beck Depression Inventory II (BDI-II), Athens Insomnia Scale (AIS), Generalized Anxiety Disorder (GAD-7), State-Trait Anxiety Inventory (STAI) and 15-dimensional measure of health-related quality of life (15D HRQoL) questionnaires. The prevalence of adult acne was 7.9% (n = 150) with no statistical differences between the sexes. Cases with acne presented more (18.9%) depressive symptoms (BDI-II > 14 points) compared with those without acne (9.7%) (p < 0.001). In adjusted logistic regression analyses, those with acne had a 2-fold risk (odds ratio (OR) 2.08, 95% confidence interval (95% CI) 1.23-3.38) of having depressive symptoms compared with controls. In conclusion, when treating adult acne patients, it is important to recognize the increased risk of mental health symptoms.

Efficacy of Spironolactone Compared with Doxycycline in Moderate Acne in Adult Females: Results of the Multicentre, Controlled, Randomized, Double-blind Prospective and Parallel Female Acne Spironolactone vs doxyCycline Efficacy (FASCE) Study.

Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.

A Randomized Clinical Trial to Evaluate the Efficacy of an Oral Probiotic in Acne Vulgaris.

The relevance of the gut microbiota in some skin inflammatory diseases, including acne vulgaris, has been emphasized. Probiotics could play a role in the modulation of the microbiota, improving the clinical course of this disease. A 12-week randomized, double-blind, placebo-controlled, clinical trial with patients aged 12 to 30 years with acne vulgaris was conducted. The study product was a capsule composed of the probiotic Lacticaseibacillus rhamnosus (CECT 30031) and the cyanobacterium Arthrospira platensis (BEA_IDA_0074B). Patients with improvement in the Acne Global Severity Scale were 10/34 (29.41%) in the placebo group compared with 20/40 (50%) in the probiotic group (p = 0.03). A significant reduction (p = 0.03) in the number of non-inflammatory acne lesions was observed in the probiotic group (-18.60 [-24.38 to -12.82]) vs the placebo group (-10.54 [-17.43 to -3.66]). Regarding the number of total  lesions, a reduction almost reaching statistical significance (p = 0.06) was observed in the probiotic group (-27.94 [-36.35 to -19.53]) compared with the placebo group (-18.31 [-28.21 to -8.41]). In addition, patients with improvement attending the Global Acne Grading System were 7/34 (20.58%) in the placebo group vs 17/40 (42.50%) in the probiotic group (p = 0.02). The number of adverse events was similar in both groups. The probiotic used in this study was effective and well tolerated, and it should be considered for acne vulgaris patients.

Acromegaly presented with acne vulgaris: a retrospective study with 123 cases.

BACKGROUND: Acne vulgaris is a prevalent skin condition. We have found that some acromegaly patients have acne. However, no study has examined the relationship between acromegaly and acne. OBJECTIVE: To explore prevalence and correlation of adult acne in patients with acromegaly. METHODS: For this cross-sectional study, we collected questionnaires, clinical information, and laboratory test results of acromegaly patients from January 2022 to December 2022 at Huashan Hospital. Of the 133 questionnaires returned, 123 had valid responses. RESULTS: Of the 123 patients with acromegaly enrolled in this study, 54.5% had adult acne. No statistically significant difference was found in prevalence between male and female patients. 61.2% of adult acne patients reported late-onset acne. Late-onset acne patients first developed acne years before acromegaly diagnosis (mean of 5.6 years for male and 4.5 years for female patients). Some acne patients have received traditional anti-acne treatment. Moreover, 31% of the patients reported no improvement, and only 3.5% of patients claimed complete resolution of acne after treatment. Before acromegaly treatment, the prevalence of adult acne was 51.2%, with mild acne accounting for 73.0%, moderate acne accounting for 23.8%, and severe acne accounting for 3.2%. After acromegaly treatment, the prevalence of adult acne was significantly decreased to 37.4% (P = 0.007). An overall decrease in acne severity was noted, with 93.5%, 6.5%, and 0% having mild, moderate, and severe acne, respectively. A total of 83.6% of the patients had self-assessed acne remission, and 33.3% of the patients reported complete acne resolution. However, 9.0% of patients reported that their condition had worsened after acromegaly treatment. After treatment, GH, IGF-1, IGF-1 index, insulin levels, and HOMA-IR decreased significantly in all patients with acromegaly (P < 0.05). Acne remission correlated positively with IGF-1 levels, but not with GH levels. The relationship between acromegaly and acne remains to be elucidated. CONCLUSIONS: Our findings provide preliminary evidence of the high prevalence of adult acne in acromegaly patients, and a high rate of late-onset acne as well. Traditional anti-acne treatments are less effective. Acne could be considerably relieved by treating acromegaly. Acne remission positively correlated with IGF-1 decline as well, which revealed the correlation between acne and IGF-1.

Effects of depot medroxyprogesterone acetate, the copper IUD and the levonorgestrel implant on testosterone, sex hormone binding globulin and free testosterone levels: ancillary study of the ECHO randomized clinical trial.

BACKGROUND: Robust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice and development of new methods. METHODS: In this ancillary study at the East London, South Africa site of the ECHO multicentre randomized trial, we compared effects of three contraceptive methods on serum androgen levels among contraceptive users aged 18 to 35 years. Participants were allocated by centrally-managed randomization to open label depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or levonorgestrel implant. The primary outcome was free testosterone at 6 months. RESULTS: We analysed stored baseline and 6-month serum samples in 398/615 participants (DMPA-IM 131/205, IUD 135/205 and implant 132/205). Median testosterone levels at baseline were DMPA-IM 0.82, IUD 0.9 and implant 0.87 nmol/L; at 6 months, DMPA 0.68 (lower than IUD, mean percentage difference 28.35, (p <  0.001), IUD 0.86 (unchanged) and implant 0.66, lower than IUD, mean percentage difference - 22.98, p <  0.001). Median SHBG levels at baseline were DMPA 52.4, IUD 50.5 and implant 55.75 nmol/L; at 6 months, DMPA 40.65, lower than IUD (mean percentage difference 21.19, p = 0.005), IUD 49.1 (unchanged), and implant 23.35 nmol/L, lower than IUD (mean percentage difference - 50.04, p <  0.001 and than DMPA (mean percentage difference - 39.45, p <  0.001). Free testosterone levels at baseline were DMPA 10, IUD 12 and implant 11 pmol/L; at 6 months, DMPA 11, less than IUD (mean percentage difference 13.53, p = 0.047), IUD 12 and implant 14, higher than IUD (mean percentage difference 14.15, p = 0.038) and than DMPA, (mean percentage difference 29.60, p < 0.001). CONCLUSIONS: This is the first randomized trial to show lower SHBG and higher free testosterone with the levonorgestrel implant than with DMPA, and contrasts with reports of increased SHBG with combined oral ethinyl estradiol/levonorgestrel use, and reduced androgens (and impaired sexual function) reported with the etonorgestrel implant. The higher free testosterone with the LNG implant might improve sexual function, mood and bone health as well as increasing side-effects such as acne and hirsutism, and is consistent with the greater sexual activity (with respect to multiple sex partners, new sex partner and unprotected sex) with the implant compared with DMPA documented in the ECHO study. ECHO TRIAL REGISTRATION: ClinicalTrials.gov , number NCT02550067 15/09/2015. Contraception, or family planning, is central to the role of women in societies. It is most important to have accurate information on the relative side-effects of various contraceptive options in order to empower women to make informed choices regarding their preferred method. Hormonal contraceptives contain various forms of the female sex hormones, estrogens and/or progestogens. These hormones have direct effects on the users, as well as modifying the levels of the users' own circulating sex hormones, both the 'female' and the 'male' sex hormones (androgens). In this study, consenting participants requesting contraception, were allocated randomly to receive either depot medroxyprogesterone acetate (DMPA-IM) a 3-monthly progestogen injection, the copper intrauterine device (IUD), a non-hormonal contraceptive inserted within the womb, or the levonorgestrel implant, a device placed under the skin which releases a progestogen for 5 years. We measured the participants' androgen levels after 6 months, and found for the first time that the active form of testosterone (free testosterone) was 29% higher with the implant than with DMPA-IM. The level with the IUD was intermediate, and significantly different from the other two methods. This finding is relevant to the effects experienced by users of these methods, because free testosterone has effects on sexual function, bone health and mood, as well as on conditions such as acne and hair distribution patterns.

The efficacy and safety of low- versus high-fluence fractional picosecond Nd:YAG 1064-nm laser in the treatment of acne scars: A randomized split-face comparison study.

BACKGROUND: Differences in clinical efficacy based on the fluence of fractional picosecond laser treatment for acne scars are unknown. OBJECTIVE: To compare the efficacy and safety of low-fluence versus high-fluence fractional picosecond Nd:YAG 1064-nm laser treatment in acne scar patients. METHODS: In this 12-week, investigator-blinded, randomized, split-face study, 25 patients with moderate-to-severe acne scars received three sessions of high-fluence laser treatment (1.0 J/cm2 ) on one side of their face and low-fluence (0.3 J/cm2 ) on the other side every 4 weeks. Patients were assessed using acne scar counts, the scar global assessment (SGA), and the ECCA scar grading scale every 4 weeks. The histological analysis compared the acne scars obtained before and 4 weeks after treatment. RESULTS: At their last visit, 88.00% and 92.00% of the subjects achieved >30% reduction in scar counts on the low- and high-fluence sides, respectively, without a significant difference between the two sides. On both sides, the scar counts, SGA, and ECCA score significantly improved 4 weeks after the last treatment. Although the high-fluence side showed a greater reduction in scar counts (-66.73%) than the low-fluence side (-62.13%), the two sides had no significant difference in the grading scores. The high-fluence side showed significantly more severe pain and higher side-effect scores immediately and 4 weeks after treatment. Histological analysis revealed a significantly increased collagen, elastin, and vimentin expression after treatment on the low-fluence side. CONCLUSIONS: The low-fluence setting demonstrated comparable efficacy and superior safety in treating acne scars compared with the high-fluence setting.

Efficacy and safety of calcipotriol as a potential topical treatment of acne vulgaris: a randomized, controlled, triple blinded, split-face clinical trial.

BACKGROUND: Acne vulgaris is a common skin problem that may result in significant scarring and systemic comorbidities. Adverse effects and increasing resistance to available treatments urge the development of new therapeutics. Topical vitamin D analogues have been successfully used in psoriasis; however, the efficacy and safety of calcipotriol as a potential topical treatment of acne is yet to be established. OBJECTIVES: To evaluate the efficacy and safety of calcipotriol in treating acne compared with adapalene and placebo. METHODS: Sixty patients with acne were included and randomly divided into two groups of 30 patients each. Group I participants were treated by daily application of calcipotriol 0.005% cream on one facial side vs. placebo (petrolatum) over the other side. Group II were treated by daily application of adapalene 0.1% gel over one facial side vs. calcipotriol on the other. Therapeutic response was evaluated using the Japanese Acne Grading System (JAGS) and through photographic evaluation using Mean Improvement Score by Physician. RESULTS: Adapalene-treated skin gave the greatest improvement and the highest patient satisfaction compared with skin treated with calcipotriol or placebo (P = 0.001). Nonetheless, the calcipotriol-treated side showed a significantly greater reduction in post-treatment JAGS score and much greater satisfaction than placebo. As treatment continued, improved tolerability to calcipotriol was noted, with comparable side-effects between the three study arms. CONCLUSIONS: Calcipotriol seems to be a promising new safe topical therapeutic option for acne. However, adapalene is still superior in efficacy, tolerability and patient satisfaction.

Facial adult female acne in China: An analysis based on artificial intelligence over one million.

BACKGROUND: To further clarify the acne profile of Chinese adult women, we included 1,156,703 adult women. An artificial intelligence algorithm was used to analyze images taken by high-resolution mobile phones to further explore acne levels in Chinese adult women. METHOD: In this study, we assessed the severity of acne by evaluating patients' selfies through a smartphone application. Furthermore, we gathered basic user information through a questionnaire, including details such as age, gender, skin sensitivity, and dietary habits. RESULTS: This study showed a gradual decrease in acne severity from the age of 25 years. A trough was reached between the ages of 40 and 44, followed by a gradual increase in acne severity. In terms of skin problems and acne severity, we have found that oily skin, hypersensitive skin, frequent makeup application and unhealthy dietary habits can affect the severity of acne. For environment and acne severity, we observed that developed city levels, cold seasons and high altitude and strong radiation affect acne severity in adult women. For the results of the AI analyses, the severity of blackheads, pores, dark circles and skin roughness were positively associated with acne severity in adult women. CONCLUSIONS: AI analysis of high-res phone images in Chinese adult women reveals acne severity trends. Severity decreases after 25, hits a low at 40-44, then gradually rises. Skin type, sensitivity, makeup, diet, urbanization, seasons, altitude, and radiation impact acne. Blackheads, pores, dark circles, and skin roughness are linked to acne severity. These findings inform personalized skincare and public health strategies for adult women.