UNASSIGNED: Acne is a chronic inflammatory skin disease that affects the pilosebaceous follicle and is influenced by heredity, hormones, inflammation, and the environment. At present, the recognized pathogenesis mainly includes four categories: excessive sebum secretion, excessive Cutibacterium acnes proliferation, excessive keratinization of sebaceous glands in hair follicles, and inflammatory mechanisms. Previous studies have found that DNA methylation is closely related to some chronic inflammatory skin diseases, and there is evidence that DNA methylation is controlled by genetic factors, making us want to know the relationship between DNA methylation, genetic variation and acne.
UNASSIGNED: In our previous study, we performed genome-wide DNA methylation analysis in peripheral blood samples from 44 patients with severe acne and 44 unaffected normal subjects, and identified 23 differentially methylated probes (DMPs). In this study, we identified single nucleotide polymorphisms (SNPs) associated with severe acne by genome-wide association analysis in these 88 samples. To test the association between SNPs and DMPs, we conducted DNA methylation quantitative trait loci (methQTL) analysis. Next, causal inference testing (CIT) was used to determine whether genetic variation influences DNA methylation, which impacts disease phenotypes.
UNASSIGNED: We found 38,269 SNPs associated with severe acne. By methQTL analysis, we obtained 24 SNP-CpG pairs that reached the threshold (FDR < 0.05), which included 7 unique CpGs and 22 unique methQTL SNPs. After CIT analysis, we found that 11 out of 24 pairs of SNP-CpG showed a weakened SNP effect after adjustment for methylation, indicating a methylation-mediated relationship between SNPs and severe acne. These 11 SNP-CpG pairs consist of four unique CpG sites and 11 SNPs, of which three CpG sites, cg03020863, cg20652636, and cg19964325, are located on the gene body of PDGFD, the intron of SH2D6, and the 5\'UTR of the IL1R1 gene, respectively.
UNASSIGNED: During this study, the DNA methylation of certain genes was found to be influenced by genetic factors and mediated the risk of severe acne in a young Chinese male population, providing a new perspective on the pathogenesis of severe acne.

Post-acne scarring in severe acne is a major aesthetic problem that can impair a patient\'s quality of life. It has been pointed out that blocking mast cell function with tranilast can prevent or minimize scarring and can be a satisfactory therapeutic strategy. Mast cells are prominent in acne lesions, and their involvement in scar formation has also been specified. Here, we discuss the importance of mast cell control in suppressing post-acne scar formation.

UNASSIGNED: We evaluated the efficacy and safety of trifarotene plus oral doxycycline in acne.
UNASSIGNED: This was a randomized (2:1 ratio) 12-week, double-blind study of once-daily trifarotene cream 50µg/g plus enteric-coated doxycycline 120mg (T+D) versus trifarotene vehicle and doxycycline placebo (V+P). Patients were aged 12 years or older with severe facial acne (≥20 inflammatory lesions, 30 to 120 non-inflammatory lesions, and ≤4 nodules). Efficacy outcomes included change from baseline in lesion counts and success (score of 0/1 with ≥2 grade improvement) on investigator global assessment (IGA). Safety was assessed by adverse events and local tolerability.
UNASSIGNED: The study enrolled 133 subjects in the T+D group and 69 subjects in the V+P group. The population was balanced, with an approximately even ratio of adolescent (12-17 years) and adult (≥18 years) subjects. The absolute change in lesion counts from baseline were: -69.1 T+D versus -48.1 V+P for total lesions, -29.4 T+D versus -19.5 V+P for inflammatory lesions, and -39.5 T+D versus -28.2 for non-inflammatory lesions (P<0.0001 for all). Success was achieved by 31.7 percent of subjects in the T+D group versus 15.8 percent in the V+P group (P=0.0107). The safety and tolerability profiles were comparable between the T+D and V+P arms.
UNASSIGNED: T+D was demonstrated to be safe and efficacious as a treatment option for patients with severe acne.

Isotretinoin is one of the first-line medications for the treatment of acne. One of the reported side effects of isotretinoin is thrombocytopenia, in addition to other abnormalities such as incomplete blood count. However, reports on thrombocytosis associated with isotretinoin are controversial. The present report discusses the case of a patient with acne vulgaris who was treated with isotretinoin and consequently suffered from isotretinoin-induced thrombocytosis. A 20-year-old female patient was diagnosed with acne vulgaris and started treatment with systemic isotretinoin (20 mg once daily) for one month. A baseline complete blood count was performed, as well as another blood count after one month of medication administration. Platelet count was recorded at each visit. The baseline platelet count was within the normal range; however, it was found to be elevated after one month of treatment. Accordingly, the medication was discontinued, and the platelet count returned to normal levels after one month, as measured during the monthly visit. The patient also experienced seizure episodes during treatment, which did not cease with the treatment discontinuation. Although isotretinoin-induced thrombocytosis is considered a rare side-effect for isotretinoin, it should be routinely monitored in high-risk patients and those undergoing surgeries. Further prospective studies on isotretinoin-induced thrombocytosis need to be conducted to gain a deeper insight into the various aspects related to the condition.

UNASSIGNED: Androgens acting through the androgen receptor play a crucial role in the pathogenesis of acne. This study aimed to identify whether two key genes (CYP21A2 and CYP19A1) involved in the synthesis and metabolism of androgens were associated with Pillsbury III-IV severe acne vulgaris.
UNASSIGNED: We carried out a standard questionnaire survey about acne and enlisted 600 Pillsbury III-IV severe acne vulgaris patients and 652 healthy controls of Han Chinese descent from Yunnan, China in the study. Twenty-two single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot assay and analyzed for association with severe acne.
UNASSIGNED: There was no significant difference in gender between the two groups (P = 0.085), and the age of the acne case group was significantly lower than that of the control group (P < 0.001). Our results revealed that only two SNPs, rs6474 (p.Arg102Lys) (P = 0.001) and rs6465 (P = 0.025) of the CYP21A2 gene were significantly associated with severe acne among the Han Chinese. When subjects were divided into males and females, significant associations were observed only in male patients with severe acne vulgaris for four variants: CYP21A2 rs6474 (p.Arg102Lys) (P = 0.002); CYP21A2 rs6465 (P = 0.012); CYP19A1 rs8023263 (P = 0.037); and CYP19A1 rs2470152 (P = 0.007). Haplotype analyses showed that the distribution of CYP21A2 haplotypes was significantly associated with male patients, while no association of CYP19A1 haplotypes was observed. The structure of the human CYP21A2 consists of two substrate binding sites and one substrate access channel.
UNASSIGNED: This study shed a light on a potentially important effect of CYP21A2 and CYP19A1 genes in severe acne vulgaris in the Han Chinese, especially for male patients. Future studies using independently verified datasets from a broader geographical spectrum will be valuable in identifying the causal and functional variants responsible for severe acne vulgaris within the CYP19A1 and CYP21A2 genes.

BACKGROUND: 5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) is increasingly used to control severe acne. However, its impact on skin microbiota remains uncertain.
OBJECTIVE: We aimed to compare the makeup, diversity, and function of the microbiota in pilosebaceous units of patients with severe acne before and after ALA-PDT.
METHODS: A longitudinal cohort study was performed on 11 participants with severe facial acne. All patients were given 5%ALA-PDT every two weeks for three sessions in total. The contents of lesions were sampled for metagenomic sequencing at baseline and two weeks after the first ALA-PDT session.
RESULTS: Cutibacterium acnes was the most dominant species followed by Staphylococcus epidermidis and Pseudomonas fluorescens. Treatment with ALA-PDT led to clinical improvements in acne severity concurrent with a significant reduction in the relative abundance of C. acnes, while P. fluorescens increased significantly after ALA-PDT. No significant change was identified in other species. ALA-PDT administration was associated with an increased microbiota diversity and reductions in the relative abundance of the functional genes involved in energy metabolism and DNA replication.
CONCLUSIONS: ALA-PDT plays a therapeutic role by killing C. acnes, increasing P. fluorescens and the microbiome diversity, while inhibiting the function of microbiota in pilosebaceous units of severe acne.

Acne is a chronic inflammatory relapsing disease that affect predominantly adolescents, with scarring as a frequent sequele. Early and appropriate therapy allows better management of the disease, longer remission, scars risk reduction, and improvement of quality of life. According to therapeutic algorithm, systemic isotretinoin can be used in severe acne and also in moderate forms resistant to other systemic treatments. The aims of this real-life observational study were to determine and compare the effectiveness of isotretinoin evaluated by Global Acne Grading System and Acne Quality of Life in moderate and in severe acne, correlation between efficacy and cumulative dose of isotretinoin, tolerability, and recurrence rate. Moreover, the differences in efficacy and tolerability between male and female patients were compared. The treatment with systemic isotretinoin led to an improvement in acne severity and quality of life in all observed subjects.

OBJECTIVE: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome encompasses heterogeneous dermatological manifestations, mainly palmoplantar pustulosis (PPP) and severe acne (SA). This study aims to explore the necessity of stratified management according to skin lesions.
METHODS: In a cohort of SAPHO patients, we compared the demographic, clinical, and scintigraphic characteristics of the SAPHO patients whose skin lesion was PPP or SA.
RESULTS: A total of 249 patients were included (227 affected by PPP and 22 affected by SA). Patients with SA were younger at onset (20, interquartile ranges (IQR) 15-30 vs. 37, IQR 30-46 years old; p < 0.001) and enrollment (35, IQR 25-38 vs. 41, IQR 33-50 years old; p = 0.001), and they had a prolonged disease duration (88.5 months, IQR 18.7-216.0 vs. 16.0, IQR 7.0-48.0 months; p < 0.001) and time needed for diagnosis (7.5, IQR 2.0-19.0 vs. 1.0, IQR 1.0-4.0 years; p < 0.001). Adjusted by age, sex, and disease duration, SA was significantly associated with more disease-modifying anti-rheumatic drug (DMARD) use (adjusted odds ratio (OR) 3.72; 95% confidence interval (CI) 1.23, 12.62; p = 0.019) and more sternoclavicular joint involvement (adjusted OR 5.91; 95% CI 1.17, 61.3; p = 0.030) in two separate Firth\'s logistic regression models.
CONCLUSIONS: SAPHO patients affected by PPP or SA as the only skin lesion may have different epidemiologic features, osteoarticular manifestations, and treatment history.Key Points• SAPHO patients with PPP or SA were heterogenous in both demographic, clinical, and imaging features.• SAPHO patients with SA were mainly male and had a significantly younger age and longer duration of symptoms before diagnosis.• SA in SAPHO patients was significantly associated with more sternoclavicular involvement and more DMARD use history.

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has been described as an effective treatment for severe acne. However, very little evidence exists on the optimal concentration of ALA used in PDT for severe acne.
OBJECTIVE: To compare the efficacy and safety of PDT with 5% ALA vs 10% ALA in severe acne.
METHODS: Twenty-three patients with severe facial acne were randomly assigned to receive PDT with 5% ALA or 10% ALA on the left or right side of the face. Four PDT sessions were conducted with a light dose of 96 J/cm2 . The reduction rates of lesion counts between the two groups were compared at the week-4 and week-12 follow-up visits. Effective rate at the week-12 visit was the primary clinical outcome. Pain and other side effects were evaluated at each visit.
RESULTS: The decrease in inflammatory lesions in the 10% ALA group was greater than that in the 5% ALA group at both week-4 (79.2% vs 62.5%, P = 0.009) and week-12 follow-up visits (88.5% vs 78.3%, P = 0.018), while the decrease in noninflammatory lesion counts between the two groups was not statistically significant at each follow-up visit. The effective rate in the 10% ALA group was significantly higher than that in the 5% ALA group (95.7% vs 69.6%, P = 0.02). No significant difference was observed in pain scores between the two groups except in the first treatment session.
CONCLUSIONS: Photodynamic therapy using 10% ALA was more effective for severe acne than PDT using 5% ALA.

OBJECTIVE: Hormonal imbalance early in life is thought to be associated with breast cancer risk. Severe acne may arise from hormonal imbalance and could serve as an indicator of increased breast cancer risk. We explored whether severe acne was associated with incident breast cancer.
METHODS: We used data from the Sister Study, a large (n = 50,884) prospective cohort of women who had a sister diagnosed with breast cancer, but who were free of breast cancer themselves at baseline. Participants completed a structured questionnaire that included demographics, lifestyle factors, and medical history, including any diagnosis of severe acne. Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of severe acne and breast cancer (invasive disease or ductal carcinoma in situ).
RESULTS: During an average of 8.4 years of follow-up, 3049 breast cancer cases were diagnosed. Ever being diagnosed with severe acne was associated with a higher risk of breast cancer (HR 1.23; 95% CI 0.98, 1.54), particularly in women who were diagnosed prior to age 18 years (HR 1.40; 95% CI 1.04, 1.90). Results were similar when limited to invasive cancers.
CONCLUSIONS: Our study supports a non-significant positive association between severe acne-a potential marker of hormonal imbalance-and breast cancer risk. These findings suggest that severe acne, when considered along with other risk factors, could help to identify women who may be at a higher risk of breast cancer.