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.

Treatments for Moderate-to-Severe Acne Vulgaris: A Systematic Review and Network Meta-analysis.

BACKGROUND: Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne treatments has not been systematically examined. METHODS: A systematic literature review (SLR) was conducted to identify randomized controlled trials of ≥4 weeks of treatment (topical, oral, physical, or combinations) for moderate-to-severe facial acne in patients aged ≥9 years. Efficacy outcomes included: percentage of patients achieving ≥2-grade reduction from baseline and “clear” or “almost clear” for global severity score (treatment success); absolute change in inflammatory (ILs reduction); and noninflammatory lesion counts (NILs reduction). A random-effects network meta-analysis (NMA) was conducted for the efficacy outcomes. Treatments were ranked with posterior rank plots and surface under cumulative ranking values.  Results: Eighty-five studies were included in the SLR/NMA. Topical triple-agent fixed-dose combination (FDC) gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments with oral antibiotics (TOA3) consistently ranked in the top 3 treatments. Topical triple-agent FDC gel was numerically superior to TOA3 for treatment success (log-odds ratios: 1.84 [95% credible interval (CrI) 1.36 to 2.29]) and 1.69 (95% CrI: 1.01 to 2.32) vs placebo/vehicle). TOA3 was numerically superior to topical triple-agent FDC gel for reduction of ILs (mean difference: -8.21 [-10.33 to -6.13]) and -10.40 [-13.44 to -7.14] vs placebo/vehicle) and NILs (mean difference: -13.41 [-16.69 to -10.32] and -17.74 [-22.56 to -12.85] vs placebo/vehicle). CONCLUSIONS: Based on this SLR/NMA, topical triple-agent FDC gel was the most efficacious and safe treatment for moderate-to-severe acne. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8148.

Pediatric Acne Vulgaris: A Guide for Recognition, Examination, Referral, and Treatment.

Acne is a common skin condition in adolescent patients but much less common in childhood. Pediatric providers should be familiar with the varying presentations in the pediatric population and recognize when additional physical signs of hyperandrogenism are present. This article details the pathogenesis and presentation of acne in infancy, mid-childhood, and preadolescence. The differential diagnosis is discussed and recommendations for initial workup, referral, and treatment are provided. [Pediatr Ann. 2024;53(4):e115-e120.].

A Silymarin Antioxidant Serum Improves Facial Acne Alone and as Part of a Treatment Regimen.

BACKGROUND: Silymarin is an antioxidant that can protect against free radicals that cause premature signs of aging and oil oxidation that may contribute to breakouts. AIMS: The objective of these studies was to evaluate a silymarin antioxidant serum alone and in combination with a prescription acne treatment regimen in improving facial appearance in blemish-prone skin.  Methods: Two international studies were conducted. A 12-week study in Brazil enrolled 56 subjects to examine the effect of silymarin antioxidant serum on facial acne. Clinical grading on acne lesions, skin tone, clarity, and postinflammatory hyperpigmentation (PIH) were conducted. In addition, consumer self-assessment, analysis for markers of lipid peroxidation, and sebumeter analysis were completed. Another Unites States (US)/German study enrolled 40 subjects who were on topical prescription acne medications to which silymarin antioxidant serum was added. Acne lesion counts, tolerability, and facial appearance assessments were conducted in this study. RESULTS: The Brazilian study demonstrated a 45% reduction in inflammatory lesions and a 43% reduction in noninflammatory lesions after 12 weeks of silymarin antioxidant serum use. In addition, sebumeter testing showed a 16% reduction in oiliness at week 1. The US/German study showed the benefits of the serum in persons already on prescription acne therapy by reducing facial erythema by 60%, dryness by 49%, and scaling by 67%. CONCLUSION: Silymarin is shown in clinical testing to have significant benefits in reducing lipid peroxidation, oiliness, and PIH, and in improving key markers of skin aging. Additionally, the serum can be used alone or as an adjunctive treatment in acne therapy to further benefit aging, acne-prone skin. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8120.

Acne and Pregnancy: A Clinical Review and Practice Pearls.

Acne vulgaris is a common condition that routinely affects females of childbearing age. Taking into consideration the reproductive journey of women when treating acne is of paramount importance given the safety concerns to both the mother and the fetus associated with certain medications. Therefore, careful consideration of therapeutic choices during pregnancy is crucial. Herein, we summarize the safety of acne treatments during pregnancy and offer practical clinical pearls for routine dermatology practice.

Early and Sustained Acne Lesion Reductions With Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel.

BACKGROUND: A once-daily, three-pronged approach using an antibiotic, antibacterial, and retinoid may provide faster acne improvement versus monotherapy or dual-combination products. This post hoc analysis compared threshold acne lesion reductions with clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel—the first FDA-approved triple-combination topical acne product—to its dyads and vehicle. METHODS: Phase 2 (N=741; NCT03170388) and phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, 12-week studies randomized participants aged ≥9 years with moderate-to-severe acne to once-daily CAB or vehicle gel; the phase 2 study included three additional dyad gel arms. The pooled percentage of participants achieving ≥33%, ≥50%, and ≥75% reduction in inflammatory and noninflammatory acne lesions was evaluated. RESULTS: As early as week 4 in the phase 2 study, ≥33% reduction in inflammatory lesions occurred in a significantly greater percentage of CAB gel-treated participants (82.7%) than with the 3 dyads and vehicle (61.1-69.8%; P<0.05, all). These early reductions were sustained throughout the study, with significantly (P<0.05) more CAB-treated participants achieving ≥50% reduction in inflammatory lesions versus dyads and vehicle from weeks 4-12. By week 12, CAB led to substantial reductions of ≥75% in significantly more participants than dyads and vehicle (65.8% vs 49.9-51.2% and 21.6%; P<0.05, all). Similar trends were observed for noninflammatory lesions in the phase 2 study and for inflammatory and noninflammatory lesions in the phase 3 studies. CONCLUSIONS: Lesion count reductions were significantly greater with CAB versus its dyads and vehicle gel as early as week 4, with substantial reductions observed after 12 weeks of treatment. This faster-acting and sustained efficacy of CAB gel—coupled with its optimized formulation, once-daily dosing, and tolerability—may positively impact treatment adherence. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7907.

Hidradenitis Suppurativa-Related Autoinflammatory Syndromes: An Updated Review on the Clinics, Genetics, and Treatment of Pyoderma gangrenosum, Acne and Suppurative Hidradenitis (PASH), Pyogenic Arthritis, Pyoderma gangrenosum, Acne and Suppurative Hidradenitis (PAPASH), Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO), and Rarer Forms.

Hidradenitis suppurativa (HS) is an autoinflammatory skin disorder of the terminal hair follicle, which can present in sporadic, familial, or syndromic form. A classification has been proposed for the latter, distinguishing cases associated with a known genetic condition, with follicular keratinization disorders or with autoinflammatory diseases. This review focuses on the clinical and genetic features of those entities (ie, pyoderma gangrenosum [PG], acne and HS; PG, acne, pyogenic arthritis and HS; psoriatic arthritis, PG, acne and HS; synovitis, acne, pustulosis, hyperostosis, osteitis; and so forth) for which the collective term HS-related autoinflammatory syndromes is proposed.

Benefit of Topical Combination Therapy for Acne: Analyzing Effect Size Using Number Needed to Treat.

BACKGROUND: Topical acne trials often are confounded by high vehicle response rates and differing outcome measures, making it difficult to compare treatments. Number needed to treat (NNT) can be a simple, clinically meaningful way to indirectly compare treatment options without head-to-head data. NNT is the number of patients who need to be treated with an intervention to observe one additional patient successfully achieving a desired outcome versus vehicle/placebo. While treatment attributes such as adverse events may not be captured, lower NNT is a good indicator of a more effective treatment. METHODS: Following a search of combination topical treatments for acne vulgaris, all treatments that reported pivotal trial efficacy data consistent with the 2018 FDA definition of success were included in NNT analyses.  Results: Of 13 treatments, 7 reported 12-week treatment success rates in 11 phase 3 trials, with similar baseline demographics/disease severity. Treatment success ranged from 26.8% with tretinoin 0.1%/benzoyl peroxide (BPO) 3% cream to 50% with triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel. NNTs for the triple-combination gel were 4 and 5 (from 2 pivotal trials). Adapalene 0.3%/BPO 2.5% gel had an NNT of 5. Tretinoin/BPO had the largest range between trials, with NNTs of 4 and 9. The other 4 treatments had NNTs ranging from 6 to 8. CONCLUSION: A comparison of combination topical acne treatment trial data, using the same treatment outcome and similar patient populations, resulted in triple-combination clindamycin phosphate/adapalene/BPO gel and adapalene/BPO gel having the most favorable NNTs.J Drugs Dermatol. 2024;23(2):42-49.  doi:10.36849/JDD.7927.

INDIVIDUAL ARTICLE: Antibiotic Stewardship in Acne: 2023 Update.

Antibiotics, topical and oral, are a cornerstone in the treatment of acnes vulgaris specifically by targeting the skin bacterium Cutibacterium acnes. Billions of individuals have received antibiotics as part of their treatment resulting in a worldwide pandemic of antibiotic resistance not only for C. acnes but also many other pathogens. With the increasing prevalence of acne and exponentially increasing utilization of antibiotics, prescribers must urgently embrace the notion of antibiotic stewardship to maintain the efficacy of acne treatments while attenuating the rise of resistance. This paper serves as an update on C. acnes resistance to antibiotics commonly employed in the treatment of acne and the necessity of implementing benzoyl peroxide in the treatment regimen as monotherapy or combination antibiotic therapies for overcoming and preventing resistance. J Drugs Dermatol. 2024;23:1(Suppl 2):s4-10.

INDIVIDUAL ARTICLE: Impact of Acne Vulgaris and Sarecycline on Social/Emotional Functioning and Daily Activities: PROSES Study.

BACKGROUND: Concise patient-reported outcome (PRO) instruments addressing the consequences of facial acne vulgaris (AV) on patients’ functioning and activities of daily living (ADL) are needed. METHODS: A 12-week, single-arm, prospective cohort study was conducted in patients ≥9 years old with moderate/severe non-nodular facial AV prescribed sarecycline as part of usual care. The primary endpoint included AV-specific patient- and caregiver-reported outcomes assessed with the expert panel questionnaire (EPQ, developed by 10 experts using a Delphi method) in patients (>12 years) and caregivers (for patients 9-11 years). Additional assessments included parental/caregiver perspectives on children’s AV. RESULTS: A total of 253 patients completed the study. Following 12-weeks of treatment, there were significant (P ≤.0001) changes from baseline in the proportion of patients responding that they never or rarely: felt angry (31.6%), worried about AV worsening (28.9%), had thoughts about AV (20.9%), had a certain level of worries about AV (38.7%), altered their social media/selfie activity (23.7%), had an impact on real-life plans due to AV (22.9%), made efforts to hide AV (21.3%), felt picked-on/judged due to AV (15.0%), were concerned about their ability to reach future goals due to AV (13.8%), or had sleep impacted due to AV (18.2%). No significant change from baseline was observed for parent/caregiver’s understanding of the child’s AV concerns, from both patient and parent/caregiver perspectives. CONCLUSIONS: Over 12 weeks of AV management with oral sarecycline, patients reported significant reductions in AV-related effects on emotional/social functioning and ADL as measured by the EPQ, a simple PRO with potential for use in clinical practice. J Drugs Dermatol. 2024;23:1(Suppl 1):s4-11.

INDIVIDUAL ARTICLE: Sarecycline Improves Acne Severity, Symptoms, and Psychosocial Burden in Non-nodular Acne Vulgaris: PROSES Study.

BACKGROUND: Patient-reported outcomes (PROs) are emerging as a fundamental component of disease impact assessment in acne vulgaris (AV), complementing clinician-reported outcomes. No data is available on PROs for patients with AV using sarecycline in real-world settings. METHODS: A single-arm, prospective cohort study that included patients ≥9 years old diagnosed with moderate or severe non-nodular AV was implemented as part of routine care in clinical practices (N=30). Patients received oral sarecycline (60 mg, 100 mg, or 150 mg) for 12 weeks, as part of usual care. The primary endpoint was Acne Symptom and Impact Scale (ASIS) responses from patients (≥12 years) and caregivers (for patients 9-11 years) at week 12 and change from baseline (CFB). Investigator’s Global Assessment (IGA) of AV severity and adverse events (AEs) were also recorded. RESULTS: A total of 253 patients with AV completed the study (adults: 60.1%, females: 77.6%). ASIS mean scores significantly decreased (P <.0001) at week 12 for: signs (mean CFB ± standard deviation [SD]: –0.8 ± 0.7), impact (–1.0 ± 1.0), emotional impact (–1.2 ± 1.1), and social impact (0.6 ± 1.1). Significant reductions in AV severity (P <.0001) were reported by patients and caregivers. The IGA success rate was 58.9% and physician satisfaction with treatment outcomes was 88.1%. A total of 31 (10.3%) patients reported ≥1 AE during the study. CONCLUSIONS: Patients with moderate-to-severe AV receiving acne management with an oral antibiotic for 12 weeks experienced a significant improvement in AV-related symptoms and psychosocial burden. J Drugs Dermatol. 2024;23:1(Suppl 1):s12-18.

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.

Relationship between elevated serum decorin levels and acne vulgaris in women with PCOS.

OBJECTIVE: The primary aim of this study was to investigate the serum levels of decorin, a small leucine-rich proteoglycan, in women diagnosed with polycystic ovary syndrome (PCOS) and concurrently presenting with moderate to severe acne vulgaris. PATIENTS AND METHODS: Sixty patients with acne vulgaris symptoms, subsequently diagnosed with PCOS according to the revised Rotterdam criteria, were enrolled in the study. Acne severity was assessed using the acne global severity scale (AGSS), with patients fitting AGSS category 4 (moderate) and 5 (severe) grouped into two separate cohorts of 30 individuals each. The moderate acne group comprised patients with few inflammatory lesions and a minor nodule alongside predominantly non-inflammatory lesions, whereas the severe group contained patients with multiple nodules and a mix of non-inflammatory and inflammatory lesions. A control group of twenty healthy women without acne vulgaris or PCOS was also established. The study measured serum testosterone, follicle-stimulating hormone (FSH), Luteinizing Hormone (LH), and insulin levels, and calculated insulin resistance via the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) formula. Quantitative sandwich enzyme immunoassay was employed to determine decorin levels from venous blood samples. RESULTS: While age, body mass index (BMI), serum FSH, LH, testosterone, and HOMA-IR values demonstrated similarity between the moderate and severe acne cohorts, comparisons between the control and both acne groups (AGSS-4 and AGSS-5) revealed significantly elevated values in the latter, excluding age, BMI, and FSH. Importantly, the serum decorin levels in both acne groups were substantially higher than in controls. A significant positive correlation was observed between serum decorin levels and both HOMA-IR (r=7.88, p<0.01) and testosterone (r=0.813, p<0.01). CONCLUSIONS: This study suggests that elevated circulating decorin levels play a pivotal role in the manifestation of acne vulgaris in women with PCOS.

Integrative bioinformatics and experimental validation of hub genetic markers in acne vulgaris: Toward personalized diagnostic and therapeutic strategies.

BACKGROUND: Acne vulgaris is a widespread chronic inflammatory dermatological condition. The precise molecular and genetic mechanisms of its pathogenesis remain incompletely understood. This research synthesizes existing databases, targeting a comprehensive exploration of core genetic markers. METHODS: Gene expression datasets (GSE6475, GSE108110, and GSE53795) were retrieved from the GEO. Differentially expressed genes (DEGs) were identified using the limma package. Enrichment analyses were conducted using GSVA for pathway assessment and clusterProfiler for GO and KEGG analyses. PPI networks and immune cell infiltration were analyzed using the STRING database and ssGSEA, respectively. We investigated the correlation between hub gene biomarkers and immune cell infiltration using Spearman's rank analysis. ROC curve analysis validated the hub genes' diagnostic accuracy. miRNet, TarBase v8.0, and ChEA3 identified miRNA/transcription factor-gene interactions, while DrugBank delineated drug-gene interactions. Experiments utilized HaCaT cells stimulated with Propionibacterium acnes, treated with retinoic acid and methotrexate, and evaluated using RT-qPCR, ELISA, western blot, lentiviral transduction, CCK-8, wound-healing, and transwell assays. RESULTS: There were 104 genes with consistent differences across the three datasets of paired acne and normal skin. Functional analyses emphasized the significant enrichment of these DEGs in immune-related pathways. PPI network analysis pinpointed hub genes PTPRC, CXCL8, ITGB2, and MMP9 as central players in acne pathogenesis. Elevated levels of specific immune cell infiltration in acne lesions corroborated the inflammatory nature of the disease. ROC curve analysis identified the acne diagnostic potential of four hub genes. Key miRNAs, particularly hsa-mir-124-3p, and central transcription factors like TFEC were noted as significant regulators. In vitro validation using HaCaT cells confirmed the upregulation of hub genes following Propionibacterium acnes exposure, while CXCL8 knockdown reduced pro-inflammatory cytokines, cell proliferation, and migration. DrugBank insights led to the exploration of retinoic acid and methotrexate, both of which mitigated gene expression upsurge and inflammatory mediator secretion. CONCLUSION: This comprehensive study elucidated pivotal genes associated with acne pathogenesis, notably PTPRC, CXCL8, ITGB2, and MMP9. The findings underscore potential biomarkers, therapeutic targets, and the therapeutic potential of agents like retinoic acid and methotrexate. The congruence between bioinformatics and experimental validations suggests promising avenues for personalized acne treatments.

An updated clinico-investigative approach to diagnosis of cutaneous hyperandrogenism in relation to adult female acne, female pattern alopecia & hirsutism a primer for dermatologists.

INTRODUCTION: Hyperandrogenism is a clinical state consequent to excess androgen production by the ovary, adrenals, or increased peripheral conversion of androgens. The varied manifestations of hyperandrogenism include seborrhea, acne, infertility, hirsutism, or overt virilization of which adult female acne, hirsutism, and female pattern hair loss are of clinical relevance to dermatologists. AREAS COVERED: We limited our narrative review to literature published during period from 1 January 1985 to Dec 2022 and searched PubMed/MEDLINE, Web of Science (WOS), Scopus, and Embase databases with main search keywords were 'Hyperandrogenism,' 'Female,' 'Biochemical,' 'Dermatological', and 'Dermatology.' We detail the common etiological causes, nuances in interpretation of biochemical tests and imaging tools, followed by an algorithmic approach which can help avoid extensive tests and diagnose the common causes of hyperandrogenism. EXPERT OPINION: Based on current data, total testosterone, sex hormone binding globulin, DHEAS, prolactin, free androgen index, and peripheral androgenic metabolites like 3-alpha diol and androsterone glucuronide are ideal tests though not all are required in all patients. Abnormalities in these biochemical investigations may require radiological examination for further clarification. Total testosterone levels can help delineate broadly the varied causes of hyperandrogenism. Serum AMH could be used for defining PCOM in adults.