Prevalence of antimicrobial-resistant Cutibacterium isolates and development of multiplex PCR method for Cutibacterium species identification.

INTRODUCTION: Cutibacterium species such as C. acnes, C. avidum, and C. granulosum are known anaerobic skin inhabitants and often cause surgical site infections. These species are genetically similar and are difficult to identify rapidly. In addition, their pathogenicity and antimicrobial resistance remain unknown. In this study, antimicrobial resistance in Cutibacterium isolates was studied and a multiplex PCR method for their identification was developed. METHODS: A total of 497 C. acnes, 71 C. avidum, and 25 C. granulosum strains which were isolated from the acne pustule and infectious regions, were used. RESULTS: The antimicrobial resistance rates of C. acnes, C. avidum, and C. granulosum strains isolated from patients with acne vulgaris were higher than those of strains isolated from patients with infectious diseases. In particular, macrolide-clindamycin-resistant strains were isolated most frequently from all species. Among the resistant strains, strains with 23S rRNA mutations were the most common in C. acnes (24.3%, 71/292), whereas C. avidum and C. granulosum strains were most frequently found with erm(X). For the first time, a C. granulosum strain carrying pTZC1, which codes erm(50) and tet(W), was isolated from patients with acne vulgaris. Regarding the rapid identification of causative pathogens from infectious regions, three Cutibacterium species were identified with 100% sensitivity and specificity using multiplex PCR method. CONCLUSIONS: Our data showed that antimicrobial resistance differed among Cutibacterium species. The multiplex PCR method may contribute to the rapid detection of Cutibacterium species and selection of appropriate antimicrobial agents.

Design and experimental evaluation of enhanced diffraction efficiency of lanthanum-based material coated laminar-type gratings in the boron K-emission region.

Numerical and experimental studies have been performed to evaluate the enhancement of diffraction efficiency of diffraction gratings around B $K$-emission by overcoating lanthanum series layers on conventional metal-coated laminar-type gratings. We propose an optical design method based on the concept of spectral flux given by collection efficiency and diffraction efficiency. A diffraction grating with a small angle of incidence provides an advantage to soft x-ray spectrographs because it collects the emission at a larger solid angle compared to that of conventional grazing incidence diffraction gratings. Numerical calculations indicated that La and ${\rm{La}}{{\rm{F}}_3}$ were promising as overcoating materials on a laminar-type Ni-coated diffraction grating, and we performed an experimental study using ${\rm{La}}{{\rm{F}}_3}$ and La/C overcoatings, considering their producibility and durability. The diffraction efficiencies were measured using a reflectometer at a synchrotron facility. The diffraction efficiencies observed at 183.4 eV were 29.4% and 34.3% at angles of incidence of 85.1° and 84.9° for ${\rm{Ni}}/{\rm{La}}{{\rm{F}}_3}$ and Ni/La/C gratings, respectively.

Transferable Multidrug-Resistance Plasmid Carrying a Novel Macrolide-Clindamycin Resistance Gene, erm(50), in Cutibacterium acnes.

Antimicrobial-resistant Cutibacterium acnes strains have emerged and disseminated throughout the world. The 23S rRNA mutation and erm(X) gene are known as the major resistance determinants of macrolides and clindamycin in C. acnes We isolated eight high-level macrolide-clindamycin-resistant C. acnes strains with no known resistance determinants, such as 23S rRNA mutation and erm(X), from different acne patients in 2008 between 2013 and 2015. The aim of this study was to identify the novel mechanisms of resistance in C. acnes Whole-genome sequencing revealed the existence of a plasmid DNA, denoted pTZC1 (length, 31,440 bp), carrying the novel macrolide-clindamycin resistance gene erm(50) and tetracycline resistance gene tet(W). pTZC1 was detected in all C. acnes isolates (eight strains) exhibiting high-level macrolide-clindamycin resistance, with no known resistance determinants (MIC of clarithromycin, ≥256 µg/ml; clindamycin, ≥256 µg/ml). Transconjugation experiments demonstrated that the pTZC1 was horizontally transferred among C. acnes strains and conferred resistance to macrolides, clindamycin, and tetracyclines. Our data showed, for the first time, the existence of a transferable multidrug-resistant plasmid in C. acnes Increased prevalence of this plasmid will be a great threat to antimicrobial therapy for acne vulgaris.

Quantitative evaluation of atrophic acne scars using 3D image analysis with reflected LED light.

BACKGROUND: Methods for objective evaluation of acne scars have not been established yet. In this study, the capability of three-dimensional image analysis of acne scarring was examined. METHODS: Two dermatologists evaluated the severity and counted the number of atrophic acne scars in a defined evaluation area of each cheek (3.5 cm × 3.5 cm) of 22 subjects (age, 21-38 years). Images of the evaluation area were obtained with an Antera 3D® (Miravex Limited, Ireland) camera three times, and three parameters (affected area, volume, and max depth) were measured. Three different filters (small, medium, and large), which limit measurement targets based on the diameters of concavities, were used for measurement. The relationships between each parameter and the evaluation results of scars by dermatologists were analyzed using Spearman's correlation coefficients. RESULTS: The correlations between the evaluation results of scars by dermatologists and each parameter measured were the highest when the large filter was used. The correlation coefficients between the severity of scars by dermatologists and each of affected area, volume, and max depth were 0.736, 0.728, and 0.722, respectively, and those between scar counts and each of affected area and volume were 0.783 and 0.770, respectively. The correlations, scatter plots, and regression lines among three measurements of parameters suggested high repeatability. CONCLUSIONS: Three-dimensional image analysis has the capability to evaluate changes in the shape of scars before and after treatment quantitatively.

Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne.

Scientific advances are continually improving the knowledge of acne and contributing to the refinement of treatment options; it is important for clinicians to regularly update their practice patterns to reflect current standards. The Global Alliance to Improve Outcomes in Acne is an international group of dermatologists with an interest in acne research and education that has been meeting regularly since 2001. As a group, we have continuously evaluated the literature on acne. This supplement focuses on providing relevant clinical guidance to health care practitioners managing patients with acne, with an emphasis on areas where the evidence base may be sparse or need interpretation for daily practice.

Efficacy and safety of oral propranolol for infantile hemangioma in Japan.

BACKGROUND: There have been few reports on the efficacy and safety of oral propranolol at 3 mg/kg/day for infantile hemangioma (IH) in Japanese patients. METHODS: A multicenter, open-label phase III study was conducted to evaluate the efficacy and safety of oral propranolol solution in Japanese infants aged 35-150 days with proliferating IH. Thirty-two patients were enrolled in the study, received propranolol solution for 24 weeks at 3 mg/kg/day, and completed the study. RESULTS: The success rate (complete or nearly complete resolution) at week 24 (primary endpoint) was 78% (95%CI: 60-91%). The improvement rate since the previous visit was 100% (32/32) after week 5. Overall, the IH surface area, maximum diameter, and color intensity all decreased over time. Consistency in assessment between the centralized and the investigator on-site assessments was observed in 26 patients. Of the 32 patients, 11 needed further treatment other than the study drug. The incidence of adverse events (AE) and drug-related AE was 97% and 31%, respectively. AE that occurred in ≥two patients were either typical of propranolol use (such as blood pressure decrease) or common events in infants. AE that resulted in dose reduction were observed in two patients, but no serious AE or AE that led to study drug discontinuation were observed. CONCLUSION: Oral propranolol solution at 3 mg/kg/day is effective and safe in Japanese IH patients.

Evaluation of the efficacy of maintenance therapy for acne vulgaris using adapalene 0.1%/benzoyl peroxide 2.5% gel and benzoyl peroxide 2.5% gel for 24 weeks and assessment of atrophic acne scars using three-dimensional image analysis.

Maintenance therapy after remission of inflammation is strongly recommended in the guideline for the treatment of acne vulgaris published by the Japanese Dermatological Association. One advantage of continuing maintenance therapy is the alleviation of atrophic scarring. This study investigated the efficacy of maintenance therapy using adapalene 0.1%/benzoyl peroxide 2.5% gel and benzoyl peroxide 2.5% gel, and its effects on atrophic scarring. Overall, 126 patients were randomized to the adapalene/benzoyl peroxide group (n = 40), benzoyl peroxide group (n = 44), and control group (without maintenance treatment drugs; n = 42), and 111 of these completed a trial lasting 24 weeks. As the primary endpoint, the treatment success rate (the percentage of patients in whom the number of inflammatory lesions was maintained at ≤10) was 89.2% in the adapalene/benzoyl peroxide group, 87.5% in the benzoyl peroxide group, and 47.4% in the control group. Compared with the control group, the success rates were significantly higher in the adapalene/benzoyl peroxide and benzoyl peroxide groups (P = 0.0006 for both). As one of the secondary endpoints, the rate of change in the number of atrophic scars showed significant improvement from the baseline in the adapalene/benzoyl peroxide and benzoyl peroxide groups at week 24 (P = 0.0004 and P < 0.0001, respectively). Although the three-dimensional image analysis parameters did not change significantly from the baseline in the adapalene/benzoyl peroxide and benzoyl peroxide groups at week 24, significant worsening was noted in the control group (P = 0.0276 for affected area, P = 0.0445 for volume, and P = 0.0182 for maximum depth). Adverse drug reactions were noted in three patients in the adapalene/benzoyl peroxide group (7.5%) but not in the benzoyl peroxide group. These findings suggest that maintenance therapy using adapalene 0.1%/benzoyl peroxide 2.5% gel and benzoyl peroxide 2.5% gel is effective in preventing the worsening of scars in Japanese patients with acne vulgaris.

Multidrug Resistance Plasmid pTZC1 Could Be Pooled among Cutibacterium Strains on the Skin Surface.

Acne vulgaris is a chronic inflammatory skin disease that is exacerbated by Cutibacterium acnes. Although antimicrobials such as macrolides, clindamycin, and tetracyclines are used to treat acne caused by C. acnes, the increasing prevalence of antimicrobial-resistant C. acnes strains has become a global concern. In this study, we investigated the mechanism by which interspecies transfer of multidrug-resistant genes can lead to antimicrobial resistance. Specifically, the transfer of pTZC1 between C. acnes and C. granulosum isolated from specimens of patients with acne was investigated. Among the C. acnes and C. granulosum isolated from 10 patients with acne vulgaris, 60.0% and 70.0% of the isolates showed resistance to macrolides and clindamycin, respectively. The multidrug resistance plasmid pTZC1, which codes for macrolide-clindamycin resistance gene erm(50) and tetracycline resistance gene tet(W), was identified in both C. acnes and C. granulosum isolated from the same patient. In addition, whole-genome sequencing revealed that the pTZC1 sequences of C. acnes and C. granulosum showed 100% identity using comparative whole-genome sequencing analysis. Therefore, we hypothesize that the horizontal transfer of pTZC1 between C. acnes and C. granulosum strains may occur on the skin surface. The plasmid transfer test revealed a bidirectional transfer of pTZC1 between C. acnes and C. granulosum, and transconjugants that obtained pTZC1 exhibited multidrug resistance. In conclusion, our results revealed that the multidrug resistance plasmid pTZC1 could be transferred between C. acnes and C. granulosum. Furthermore, since pTZC1 transfer among different species may aid in the prevalence of multidrug resistant strains, antimicrobial resistance genes may have been pooled on the skin surface. IMPORTANCE The emergence of antimicrobial resistance not only in Cutibacterium acnes strain but also other skin bacteria such as Staphylococcus epidermidis is a big concern due to antimicrobial use for the treatment of acne vulgaris. Increased prevalence of macrolides-clindamycin resistant C. acnes relates to the acquisition of exogenous antimicrobial resistance genes. erm(50) is harbored by the multidrug resistance plasmid pTZC1, which has been found in C. acnes and C. granulosum strains isolated from patients with acne vulgaris. In this study, C. acnes and C. granulosum with pTZC1 were found in the same patient, and plasmid transfer between C. acnes and C. granulosum was proved by transconjugation assay. This study showed plasmid transfer between other species and the possibility of further prevalence antimicrobial resistance between Cutibacterium species.

Real-world safety and effectiveness of adalimumab in patients with hidradenitis suppurativa: A 52-week analysis of a postmarketing surveillance study in Japan.

Adalimumab is a human monoclonal antibody against tumor necrosis factor-α that was approved in Japan for the treatment of hidradenitis suppurativa (HS), a chronic recurrent inflammatory skin disease. We report the results of the final analysis of the postmarketing surveillance (PMS) study (ClinicalTrials.gov: NCT03894956), which evaluated the 52-week safety and efficacy of adalimumab for HS treatment in real-world clinical practice in Japan. This multicenter, prospective, open-label, observational study (March 2019 to May 2021) included patients with HS treated with subcutaneous adalimumab at doses following the package insert. The primary endpoint was safety, and the secondary endpoints were effectiveness, including HS clinical response (HiSCR), C-reactive protein (CRP), skin pain, and Dermatology Life Quality Index (DLQI). Of the 84 patients registered at 65 sites, 83 patients were included in the analyses. Adverse drug reactions (ADRs) were reported by 10 (12.0%) patients; two patients reported a serious ADR, including one patient with serious infection. Other safety events of special interest reported were liver disorder and dermatitis psoriasiform (one patient each). Almost all patients with ADRs were recovering or had recovered, except for one patient who experienced a serious ADR of liver disorder and died. At 12 weeks, 55.4% of patients achieved HiSCR; this increased to 60.5% and 62.8% at 24 and 52 weeks of adalimumab treatment, respectively. Significant reductions from baseline in CRP (P < 0.05), skin pain (P < 0.0001), and DLQI (P < 0.0001) were observed at all time points. The results from this PMS study demonstrated that long-term adalimumab treatment is well tolerated and effective in patients with HS in real-world clinical practice in Japan.

Acne Among Japanese Patients with Atopic Dermatitis Receiving Upadacitinib in the Phase 3 Rising Up Study.

INTRODUCTION: Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is used to treat moderate-to-severe atopic dermatitis (AD). Acne is the most common treatment-emergent adverse event in patients with AD treated with upadacitinib. In this post hoc analysis, we describe the acne events in Japanese patients with AD who received upadacitinib during the Rising Up study. METHODS: In this phase 3, double-blind, 3-year trial evaluating the safety and efficacy of upadacitinib 15 mg or 30 mg in Japanese patients with moderate-to-severe AD, patients were randomized 1:1:1 to receive upadacitinib 15 mg, 30 mg, or placebo for up to 16 weeks. At week 16, placebo-treated patients were re-randomized 1:1 to receive upadacitinib 15 mg or 30 mg. The incidence, characteristics, and management of treatment-emergent acne events up to the 52-week cutoff date were summarized. RESULTS: Among 272 patients in this analysis, the incidence of acne was higher in patients receiving upadacitinib compared with patients who received placebo. The rate of acne was higher in patients receiving upadacitinib 30 mg (32.4%) compared with those taking upadacitinib 15 mg (17.3%) during the long-term treatment period. All cases of acne were mild or moderate; no cases led to study drug discontinuation. The mean (range) of acne onset was 135.4 (7-465) days after starting study drug. Most acne occurred on the face; inflammatory papules were the most common morphology. Risk factors for acne included relevant concomitant medications (e.g., corticosteroids) started before acne onset and family and personal history of acne. Acne was generally managed with topical treatments. CONCLUSION: Mild or moderate acne reported in Japanese patients with AD receiving upadacitinib occurred in a dose-dependent manner and had a variable onset time. Acne was readily managed with topical treatments. Patients and clinicians should be aware of the risk of acne associated with upadacitinib treatment for AD. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03661138.

Increased frequency of clindamycin-resistant Cutibacterium acnes strains isolated from Japanese patients with acne vulgaris caused by the prevalence of exogenous resistance genes.

Cutibacterium acnes, a resident bacterium of the skin, is a target for antimicrobial treatment of acne vulgaris, because it exacerbates inflammation. Recently, antimicrobial-resistant C. acnes strains have been isolated worldwide, and their prevalence has led to failure of antimicrobial treatment. This study aimed to analyze the antimicrobial resistance of C. acnes strains isolated from Japanese patients with acne vulgaris who visited the hospital and dermatological clinics between 2019 and 2020. Resistance rates to roxithromycin and clindamycin increased during 2019 to 2020 compared with those during 2013 to 2018. Additionally, the proportion of doxycycline-resistant and low-susceptibility strains (minimum inhibitory concentration [MIC] ≥8 µg/mL) increased. No difference in clindamycin resistance rates between patients with and without a history of antimicrobial use was observed during 2019 to 2020, which were significantly higher for patients with a history than for patients without a history during 2016 to 2018. The proportion of high-level clindamycin-resistant strains (MIC ≥256 µg/mL) gradually increased; particularly, the resistance rate was 2.5 times higher in 2020 than that in 2013. The proportion of strains showing high-level clindamycin resistance that also have the exogenous resistance genes erm(X) or erm(50), which confer high resistance, showed a strong positive correlation (r = 0.82). Strains with the multidrug resistance plasmid pTZC1 encoding erm(50) and tet(W) genes were frequent in clinic patients. Notably, most strains with erm(X) or erm(50) were classified as single-locus sequence types A and F (traditional types IA1 and IA2). Our data show that the prevalence of antimicrobial-resistant C. acnes is increasing in patients with acne vulgaris attributable to acquisition of exogenous genes in specific strains. To control the increasing prevalence of antimicrobial-resistant strains, it is important to select the appropriate antimicrobials while taking into consideration the latest information on resistant strains.

A case of bullous pemphigoid and renal disease after dipeptidyl peptidase 4 inhibitor administration.

A 62-year-old man with type 2 diabetes was admitted because of a decrease in estimated glomerular filtration rate from 72 to 17.5 mL/min/1.73 m2 in 10 years and development of widespread bullous skin lesions. His hemoglobin A1c level had been maintained at 6.0-7.0% for 10 years with a dipeptidyl peptidase (DPP)-4 inhibitor. Skin biopsy showed typical bullous pemphigoid, and kidney biopsy showed tubulointerstitial nephritis with eosinophilic infiltration and glomerular endothelial cell proliferation. After discontinuing the DPP-4 inhibitor, skin lesions improved, and renal decline slowed. This case indicates that DPP-4 inhibitors can cause not only skin lesions but also renal disease.

Severe Erythroderma Due to Adult-onset Still's Disease-like Disease Related to Graft-versus-host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

A 35-year-old woman was treated with chemotherapy for leukemia. One year later, allogeneic hematopoietic stem cell transplantation (HSCT) was performed with umbilical cord blood. After nine months, she developed a spiking fever, sore throat, arthralgia, pleural effusion, hyperferritinemia, and persistent generalized pruritic erythema. A skin biopsy showed dyskeratotic cells in the epidermis, neutrophil infiltration in the epidermis and upper dermis, and neutrophils in the parakeratotic layer. Treatment with tocilizumab was effective. Adult-onset Still's disease (AOSD)-like disease related to graft versus-host disease (GVHD) after HSCT was suspected. Abnormal immune states related to GVHD may cause AOSD-like disease with more severe skin lesions than usual.

Increased Prevalence of Minocycline-Resistant Staphylococcus epidermidis with tet(M) by Tetracycline Use for Acne Treatment.

Staphylococcus epidermidis, a major skin bacterium, can cause opportunistic infections. Use of antimicrobial agents against Cutibacterium acnes for acne treatment becomes a risk factor for emergence of antimicrobial-resistant skin bacteria. In this study, the impact of antimicrobial treatment of acne vulgaris on S. epidermidis antimicrobial resistance was assessed. A total of 344 S. epidermidis strains isolated from patients with acne vulgaris who visited hospital (165 strains) and dermatological clinics (179 strains), respectively, were analyzed. Except for doxycycline, the resistance rates were higher in strains isolated from patients who had used antimicrobials for acne treatment than in those isolated from patients who had not used antimicrobials. The prevalence rates of strains with erm(C) from patients who used macrolides and clindamycin (hospital, 78.0%; clinics, 61.3%) and those of strains with tet(M) from patients who used tetracyclines (hospital, 27.5%; clinics, 42.4%) were significantly higher than those of strains from patients who did not use antimicrobials (p < 0.05). All strains with erm(A) (8/8) and 91.7% strains with erm(C) (156/170) showed high-level resistance to macrolides and clindamycin (MIC ≥256 µg/mL). Furthermore, almost all strains with tet(M) showed resistance to minocycline. Our results showed that the use of antimicrobials for acne treatment may lead to an increased prevalence of antimicrobial-resistant S. epidermidis. In particular, the emergence of minocycline-resistant strains with tet(M) owing to the use of tetracyclines (doxycycline and minocycline) is a critical issue. Appropriate antimicrobial use for acne treatment may be an important strategy to prevent the emergence of antimicrobial-resistant skin bacteria.

Multidrug-resistant Cutibacterium avidum isolated from patients with acne vulgaris and other infections.

OBJECTIVES: Cutibacterium avidum, a human skin commensal bacterium, rarely causes infections. It has recently been shown that Cutibacterium acnes, another member of the genus, acts as an opportunistic pathogen in surgical site infections. However, the antimicrobial susceptibility and pathogenicity of C. avidum remain unknown. METHODS: We investigated the epidemiological features and antimicrobial susceptibility of C. avidum isolated from patients with acne vulgaris and other infections. RESULTS: Cutibacterium avidum strains were isolated from patients with acne vulgaris (29 strains) and other infections (12 strains). Clarithromycin and clindamycin resistance was observed in 65.9% (27/41) of strains. In addition, ciprofloxacin resistance was observed in 34.1% (14/41) of strains, of which 13 also exhibited resistance to macrolides and clindamycin. Notably, the macrolide-clindamycin resistance gene erm(X) was found on the chromosome of 92.6% (25/27) of clindamycin-resistant strains and may be prevalent owing to transmission among C. avidum strains. Ciprofloxacin-resistant strains developed amino acid substitutions in GyrA owing to the use of antimicrobial agents. Pulsed-field gel electrophoresis (PFGE) analysis revealed that only a few strains exhibited 100% similarity. Additionally, no clustering associated with antimicrobial resistance, biofilm-forming ability or type of infection was observed. CONCLUSION: Our study revealed that erm(X) may be frequently disseminated in C. avidum, and multidrug-resistant C. avidum strains may colonise the skin of patients with acne vulgaris and other infections. Therefore, the prevalence of multidrug-resistant C. avidum and the use of antimicrobial agents for the treatment of acne vulgaris and other infections associated with C. avidum should be monitored.

Real-world safety and effectiveness of adalimumab in patients with hidradenitis suppurativa: 12-week interim analysis of post-marketing surveillance in Japan.

Hidradenitis suppurativa (HS) is a painful chronic skin disease characterized by abscesses, nodules, and tunnels in the skin. Adalimumab, a monoclonal antibody against tumor necrosis factor-α, is approved for the treatment of HS in Europe, the USA, and Japan. This multicenter, open-label, post-marketing, observational study (ClinicalTrials.gov: NCT03894956) evaluated the safety and effectiveness of adalimumab in routine clinical practice in Japan (March 2019-May 2021). Patients with HS were treated with s.c. doses of adalimumab according to the dosage described in the package insert. The primary end-point was safety (data cut-off, December 2020). Secondary end-points assessed effectiveness, including HS Clinical Response (HiSCR), skin pain, Dermatology Life Quality Index (DLQI), and C-reactive protein (CRP). Here, we report 12-week interim effectiveness results. A total of 84 eligible patients from 65 sites were enrolled; 83 patients were included in this analysis. Mean age was 42.0 years, mean body mass index was 26.9 kg/m2 , 78.3% of patients were male, 61.4% had Hurley stage III disease, 39.8% had a disease duration ≥10 years, and 7.2% had a family history of HS. The most common affected sites were the axilla (60.2%), buttocks (59.0%), and the inguinal and femoral regions (47.0%). Mean abscess and inflammatory nodule count was 13.0 (standard deviation, 12.0). Among patients with a comorbidity (57.8%), the most common were diabetes mellitus, hypertension, and chronic kidney disease. No patient reported a serious infection or any safety event of special interest. One patient died from a serious adverse event of cardiac failure unrelated to adalimumab. At week 12, 57.4% of patients achieved HiSCR, and significant reductions from baseline in skin pain, DLQI (both p < 0.0001), and CRP (p = 0.0029) were observed. These results support the administration of adalimumab as a well-tolerated and effective treatment for Japanese patients with HS in real-world clinical practice.

Disseminated cryptococcosis in a renal transplant recipient.

Skin cryptococcosis often manifests as an umbilicated papule, and chest computed tomography findings of multiple nodules and cavities are also characteristic. The combination of characteristic cutaneous manifestations and radiological findings can help clinicians make an "at-a-glance" diagnosis of disseminated cryptococcosis.

Acne management in Japan: study of patient adherence.

Obtaining good adherence to acne therapy is a challenge for all dermatologists. We studied 428 acne patients in Japan to determine the likelihood of good adherence and factors associated with medication-taking. This study utilized a simple validated questionnaire to assess risk of poor adherence; information about patient and treatment characteristics was also collected. There was an overall rate of poor adherence in 76% of subjects. Adherence to topical medication was poor in 52% of those treated with a topical agent only (n = 123). Among those taking combination therapies (n = 275), adherence to the topical portion of therapy was poor in 49% of subjects. The likelihood of poor adherence to oral medication was higher, both when administered alone (n = 30, 93% poor adherence) and when given as part of a combination regimen (n = 275, 86%). Factors with an impact on adherence included satisfaction with treatment (p = 0.023) and the experience of side effects (p = 0.027). Patients who felt they had a good understanding of acne and its treatment were more likely to have good adherence. These data suggest that there is significant room for improvement in acne adherence in Japan, as in other areas of the world, and that improved education may enhance adherence.

Increased prevalence of doxycycline low-susceptible Cutibacterium acnes isolated from acne patients in Japan caused by antimicrobial use and diversification of tetracycline resistance factors.

The prevalence of antimicrobial-resistant Cutibacterium acnes is an important concern for the antimicrobial treatment of acne vulgaris. We hypothesized that antimicrobial treatment regimens for acne vulgaris would change following the revisions in the Japanese acne treatment guidelines, which added a statement regarding appropriate antimicrobial usage. Here, we studied the changes in antimicrobial use and antimicrobial-resistant C. acnes isolated from acne patients. A total of 127 C. acnes isolates collected from 212 patients with acne between 2013 and 2018 were used. Roxithromycin and clindamycin resistance rates were approximately 50% and 40%, respectively. In contrast, the prevalence of low doxycycline-susceptible strains (minimum inhibitory concentration [MIC] ≥8 µg/mL) in 2018 (17.4%) was 5.6-fold higher than that in 2013 (3.1%). Although the number of patients with severe and moderate acne did not change, the number of patients with a history of oral tetracycline use increased. The incidence of low doxycycline-susceptible strains was high in patients with a history of oral tetracycline use. The prevalence of strains with a 16S rRNA mutation, which confers reduced susceptibility to tetracyclines, increased by 8.6-fold (12.1%) from 2016 to 2018 in comparison with the previously revised guidelines (1.4%). Furthermore, the prevalence of low susceptibility strains with two resistance factors, 16S rRNA mutation and ribosomal S10 protein substitution, also increased. Approximately 10% of strains had the exogenous resistance gene, tet(W) (2013 to 2015, 10.1%; 2016 to 2018, 8.6%), and these strains showed different susceptibility to doxycycline dependent on the expression of tet(W) (MIC range 0.5-8 µg/mL). Our data show that the antimicrobial resistance pattern in C. acnes changes according to the trend of antimicrobial usage for acne treatment. Therefore, we should pay heed to the rapid dissemination of tetracycline resistance in C. acnes owing to acquisition of 16S rRNA mutation and tet(W).

An increase in normetanephrine in hair follicles of acne lesions through the sympatho-adrenal medullary system in acne patients with anxiety.

Acne vulgaris, a chronic inflammatory skin disease, has been associated with not only sebaceous gland dysfunction but also various endogenous and exogenous stresses. Since sebaceous glands are under neuroendocrine control, including the hypothalamic-pituitary-adrenal axis and neuro-autocrine mechanisms, it remains unclear how psychological stress relates to the pathogenesis of acne. In this study, we investigated the relationship between psychological stress and catecholamine in acne lesions from 18 patients with mild or moderate acne. The State-Trait Anxiety Inventory (STAI) revealed that all patients were anxious, with six having low anxiety and 12 high anxiety. Salivary α-amylase activity (sAA), which is regulated by the sympatho-adrenal medullary (SAM) system, positively correlated with the STAI State Anxiety scores (STAI-S) and was significantly detectable in acne patients with high rather than low anxiety. In addition, the level of normetanephrine, but not metanephrine, both of which are catecholamine metabolites, in hair follicles of acne lesions also positively correlated with the STAI-S. Furthermore, the normetanephrine level was higher in patients with high rather than low anxiety, whereas there was no change in metanephrine in the hair follicles of the acne lesions. Moreover, neither the sAA nor metanephrine and normetanephrine in the acne lesions was related to acne severity in the patients. Thus, these results provide novel evidence that a SAM system-associated increase of normetanephrine level in hair follicles is involved in the acne pathology of patients with anxiety.