Clinical and cost-effectiveness of spironolactone in treating persistent facial acne in women: SAFA double-blinded RCT.

Background: Acne is common, can cause significant impact on quality of life and is a frequent reason for long-term antibiotic use. Spironolactone has been prescribed for acne in women for many years, but robust evidence is lacking. Objective: To evaluate whether spironolactone is clinically effective and cost-effective in treating acne in women. Design: Pragmatic, parallel, double-blind, randomised superiority trial. Setting: Primary and secondary healthcare and community settings (community and social media advertising). Participants: Women aged 18 years and older with facial acne persisting for at least 6 months, judged to potentially warrant oral antibiotic treatment. Interventions: Participants were randomised 1 : 1, using an independent web-based procedure, to either 50 mg/day spironolactone or matched placebo until week 6, increasing to 100 mg/day spironolactone or matched placebo until week 24. Participants continued usual topical treatment. Main outcome measures: Primary outcome was the adjusted mean difference in Acne-Specific Quality of Life symptom subscale score at 12 weeks. Secondary outcomes included Acne-Specific Quality of Life total and subscales; participant self-assessed improvement; Investigator's Global Assessment; Participant's Global Assessment; satisfaction; adverse effects and cost-effectiveness. Results: Of 1267 women assessed for eligibility, 410 were randomised (201 intervention, 209 control), 342 in the primary analysis (176 intervention, 166 control). Mean age was 29.2 years (standard deviation 7.2) and 7.9% (28/356) were from non-white backgrounds. At baseline, Investigator's Global Assessment classified acne as mild in 46%, moderate in 40% and severe in 13%. At baseline, 82.9% were using topical treatments. Over 95% of participants in both groups tolerated the treatment and increased their dose. Mean baseline Acne-Specific Quality of Life symptom subscale was 13.0 (standard deviation 4.7) across both groups. Mean scores at week 12 were 19.2 (standard deviation 6.1) for spironolactone and 17.8 (standard deviation 5.6) for placebo [difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46) adjusting for baseline variables]. Mean scores at week 24 were 21.2 (standard deviation 5.9) in spironolactone group and 17.4 (standard deviation 5.8) in placebo group [adjusted difference 3.77 (95% confidence interval 2.50 to 5.03) adjusted]. Secondary outcomes also favoured spironolactone at 12 weeks with greater differences at 24 weeks. Participants taking spironolactone were more likely than those taking placebo to report overall acne improvement at 12 weeks {72.2% vs. 67.9% [adjusted odds ratio 1.16 (95% confidence interval 0.70 to 1.91)]} and at 24 weeks {81.9% vs. 63.3% [adjusted odds ratio 2.72 (95% confidence interval 1.50 to 4.93)]}. Investigator's Global Assessment was judged successful at week 12 for 31/201 (18.5%) taking spironolactone and 9/209 (5.6%) taking placebo [adjusted odds ratio 5.18 (95% confidence interval 2.18 to 12.28)]. Satisfaction with treatment improved in 70.6% of participants taking spironolactone compared with 43.1% taking placebo [adjusted odds ratio 3.12 (95% confidence interval 1.80 to 5.41)]. Adverse reactions were similar between groups, but headaches were reported more commonly on spironolactone (20.4% vs. 12.0%). No serious adverse reactions were reported. Taking account for missing data through multiple imputation gave an incremental cost per quality-adjusted life-year of £27,879 (adjusted) compared to placebo or £2683 per quality-adjusted life-year compared to oral antibiotics. Conclusions: Spironolactone resulted in better participant-reported and investigator-reported outcomes than placebo, with greater differences at week 24 than week 12. Trial registration: This trial is registered as ISRCTN12892056 and EudraCT (2018-003630-33). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/13/02) and is published in full in Health Technology Assessment; Vol. 28, No. 56. See the NIHR Funding and Awards website for further award information.

Acne (or spots) is common and often persists into adulthood. Many people take long courses of antibiotic tablets, but concerns about antibiotic resistance mean alternatives are needed. Spironolactone is a medicine that is sometimes used for acne in women. However, we do not know whether it works. This trial aimed to answer this question. We invited women aged over 18 who had acne on their face for at least 6 months to take part via their general practitioner surgery, hospital or advertising. Women were randomly assigned to two groups: one group was given spironolactone and the other group was given identical-looking placebo ('dummy pill') daily for 24 weeks. Women in both groups could continue using acne treatments applied to the skin (gels/creams/lotions). We asked participants to rate their acne using a questionnaire called Acne-Specific Quality of Life, asked whether they felt their skin had improved and asked skin specialists to assess their skin. Four hundred and ten women took part, many of whom had had acne for a long time. Acne-Specific Quality of Life scores improved in both groups by 12 weeks but improved more in the spironolactone group at 12 and 24 weeks. When asked directly whether their skin had improved, 71% of participants in the spironolactone group said it had, compared with 43% on placebo. Skin specialists were also more likely to report that the acne had improved in the spironolactone group. Side effects were mild and similar in both groups but there were slightly more headaches on spironolactone (20% compared with 12%). Spironolactone is likely to represent value for money for the National Health Service, though this depends on a number of factors including what it is compared to. This trial suggests that spironolactone is a useful additional treatment for women with persistent acne.

A randomized, double-blind phase 2b trial to evaluate efficacy of ChAd63-KH for treatment of post kala-azar dermal leishmaniasis.

In a recent phase 2a clinical trial, the candidate leishmaniasis vaccine ChAd63-KH was shown to be safe and immunogenic in Sudanese patients with post kala-azar dermal leishmaniasis (PKDL). However, its value as a stand-alone therapeutic was unknown. To assess the therapeutic efficacy of ChAd63-KH, we conducted a randomized, double-blind, placebo-controlled phase 2b trial (ClinicalTrials.gov: NCT03969134). Primary outcomes were safety and efficacy (≥90% improvement in clinical disease). Secondary outcomes were change in severity grade and vaccine-induced immune response. 86 participants with uncomplicated PKDL of ≥6 month duration were randomized to receive ChAd63-KH (7.5 × 1010 viral particles, once by the intramuscular route) or placebo. 75 participants (87%) completed the trial as per protocol. No severe or serious adverse events were observed. At day 90 post-vaccination, 6/40 (15%) and 4/35 (11%) participants in the vaccine and placebo groups, respectively, showed ≥90% clinical improvement (risk ratio [RR] 1.31 [95% confidence interval (CI), 0.40-4.28], p = 0.742). There were also no significant differences in PKDL severity grade between study arms. Whole-blood transcriptomic analysis identified transcriptional modules associated with interferon responses and monocyte and dendritic cell activation. Thus, a single vaccination with ChAd63-KH showed no therapeutic efficacy in this subset of Sudanese patients with PKDL.

Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis.

The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available. To facilitate vaccine development, we conducted an open-label observational study to establish a controlled human infection model (CHIM) of sand fly-transmitted cutaneous leishmaniasis (CL) caused by Leishmania major. Between 24 January and 12 August 2022, we exposed 14 participants to L. major-infected Phlebotomus duboscqi. The primary objective was to demonstrate effectiveness of lesion development (take rate) and safety (absence of CL lesion at 12 months). Secondary and exploratory objectives included rate of lesion development, parasite load and analysis of local immune responses by immunohistology and spatial transcriptomics. Lesion development was terminated by therapeutic biopsy (between days 14 and 42 after bite) in ten participants with clinically compatible lesions, one of which was not confirmed by parasite detection. We estimated an overall take rate for CL development of 64% (9/14). Two of ten participants had one and one of ten participants had two lesion recurrences 4-8 months after biopsy that were treated successfully with cryotherapy. No severe or serious adverse events were recorded, but as expected, scarring due to a combination of CL and the biopsy procedure was evident. All participants were lesion free at >12-month follow-up. We provide the first comprehensive map of immune cell distribution and cytokine/chemokine expression in human CL lesions, revealing discrete immune niches. This CHIM offers opportunities for vaccine candidate selection based on human efficacy data and for a greater understanding of immune-mediated pathology. ClinicalTrials.gov identifier: NCT04512742 .

Development of a Core Outcome Measure Instrument; "LeishCOM_LCL", for Localised Cutaneous Leishmaniasis.

BACKGROUND: Localized cutaneous leishmaniasis (LCL) is a chronic ulcerating disease. A literature review identified inconsistencies in clinical trials. The aims of this study were to reach a consensus on the most important domains to measure when assessing LCL, agree on parameters to measure the domains, and develop a tool representing a Core Outcome Set (COS), for use in clinical assessment of LCL. METHODOLOGY & PRINCIPAL FINDINGS: A literature review was conducted to identify any existing COS for LCL embracing agreed Outcome Domains, i.e. what to measure and any Outcome Measurement Instruments (OMIs). As no COS was available, potential outcome domains for assessment of LCL were identified through an international collaborative approach using e-consultations and virtual discussions with expert stakeholders (n = 20) from geographically different LCL endemic countries. Subsequent judgmental validation process included a face-to-face multidisciplinary stakeholders' meeting adopting the Nominal Group Technique. A final consensual agreement on outcome domains and items required to measure these domains was established. "Clinical Cure" was defined as the ideal overall "General Concept". The five Core Outcome Domains included Signs capturing clinical morphology, diameter, and induration of an index lesion with the aid of a palpability score, Treatment Efficacy assessing percentage change in size of the lesion and re-epithelialization compared to baseline, Treatment Impact which included an investigator and patient visual analogue score, and Clinical Sequelae rating pigment change, atrophic and hypertrophic/keloid scars. It was agreed that two open-ended questions should be included to capture some aspects of Health-Related Quality of Life as a means of capturing a patient-focused approach. CONCLUSION: LeishCOM_LCL was generated to reflect a COS for LCL. This captured demographic details, agreed outcome domains and measures to assess these domains. Validation of LeishCOM_LCL will be reported in a separate paper. Development of a Patient Reported Outcome Measure will be considered in the future.

A microRNA focus on acne.

Acne (syn. acne vulgaris) is a common inflammatory skin disorder associated with puberty and adolescence. The disease is characterized by comedoneous lesions, papules, pustules, and nodules that are mostly found on the face. These lesions are caused by intricate interactions between the pilosebaceous unit and the Cutibacterium acnes (C. acnes) bacteria. Unhealthy acne and its aftereffects, like pigment changes and scarring, have a detrimental impact on one's quality of life. Recent years have seen a sharp increase in the approval of nucleic acid therapies (NATs), such as antisense oligonucleotides and short-interfering RNA medications, for rare diseases for which there are few or no effective treatments. These developments suggest that NATs may be useful in acne treatment plans down the road, as do clinical trials for microRNA (miRNA) modulation in skin contexts. We highlight promising miRNA targets for anti-acne therapy in this review. We outline the pathophysiology of acne in brief and emphasize the functions of C. acnes. Next, we concentrate on the distinct impacts of biofilm and planktonic C. acnes on a Toll-like receptor 2 axis that spans miR-146a-5p, which was recently discovered. Before discussing the potential contributions of miR-21-5p, miR-233-3p, and miR-150-5p to inflammatory axes in acne, we evaluate miR-146a-5p in sebocytes. Finally, we address patient involvement in miRNA-related acne research and translational perspectives.

International expert consensus recommendations for the use of dermocosmetics in acne.

BACKGROUND: A wide variety of dermocosmetics (products with both active skincare and cosmetic activity) are available for the management of acne vulgaris. These products are important because they may be the first line of approach for patients desiring to self-treat and they can also have beneficial effects-reducing lesion counts and improving global acne severity. When used in conjunction with medical therapy, dermocosmetics can improve tolerability and enhance results. We reviewed available evidence and combined it with our clinical experience to help guide clinicians in selecting skincare products with acne-targeting ingredients. METHODS: An international panel of dermatologists with an interest and expertise in managing acne performed a literature review, formulated clinical questions related to the role of dermocosmetics in the acne setting, used a modified GRADE approach to evaluate available evidence and then utilized an online iterative Delphi process to create consensus recommendations. It should be noted that due to the limited number of available studies, the category of dermocosmetics was evaluated rather than specific ingredients. RESULTS: The quality of evidence was found to be low to moderate. Key recommendations were made based on available evidence for the use of dermocosmetics in acne to improve acne global assessment, reduce acne lesion counts, reduce superficial skin oiliness and serve as maintenance therapy after medical treatment, while providing a good tolerability. Recommendations were also made for using dermocosmetics as adjuncts to medical treatment. CONCLUSIONS: While there is a need for better quality evidence, dermocosmetics have demonstrated some benefit for acne both when used alone in its milder clinical presentations or in maintenance post acne medication and as adjunct to acne treatments.

Cost-effectiveness of Spironolactone for Adult Female Acne (SAFA): economic evaluation alongside a randomised controlled trial.

OBJECTIVE: This study aims to estimate the cost-effectiveness of oral spironolactone plus routine topical treatment compared with routine topical treatment alone for persistent acne in adult women from a British NHS perspective over 24 weeks. DESIGN: Economic evaluation undertaken alongside a pragmatic, parallel, double-blind, randomised trial. SETTING: Primary and secondary healthcare, community and social media advertising. PARTICIPANTS: Women ≥18 years with persistent facial acne judged to warrant oral antibiotic treatment. INTERVENTIONS: Participants were randomised 1:1 to 50 mg/day spironolactone (increasing to 100 mg/day after 6 weeks) or matched placebo until week 24. Participants in both groups could continue topical treatment. MAIN OUTCOME MEASURES: Cost-utility analysis assessed incremental cost per quality-adjusted life year (QALY) using the EQ-5D-5L. Cost-effectiveness analysis estimated incremental cost per unit change on the Acne-QoL symptom subscale. Adjusted analysis included randomisation stratification variables (centre, baseline severity (investigator's global assessment, IGA <3 vs ≥3)) and baseline variables (Acne-QoL symptom subscale score, resource use costs, EQ-5D score and use of topical treatments). RESULTS: Spironolactone did not appear cost-effective in the complete case analysis (n=126 spironolactone, n=109 control), compared with no active systemic treatment (adjusted incremental cost per QALY £67 191; unadjusted £34 770). Incremental cost per QALY was £27 879 (adjusted), just below the upper National Institute for Health and Care Excellence's threshold value of £30 000, where multiple imputation took account of missing data. Incremental cost per QALY for other sensitivity analyses varied around the base-case, highlighting the degree of uncertainty. The adjusted incremental cost per point change on the Acne-QoL symptom subscale for spironolactone compared with no active systemic treatment was £38.21 (complete case analysis). CONCLUSIONS: The results demonstrate a high level of uncertainty, particularly with respect to estimates of incremental QALYs. Compared with no active systemic treatment, spironolactone was estimated to be marginally cost-effective where multiple imputation was performed but was not cost-effective in complete case analysis. TRIAL REGISTRATION NUMBER: ISRCTN registry (ISRCTN12892056).

Factors that influence women's enrolment and ongoing participation in a partially decentralised randomised controlled dermatology trial: a qualitative interview study with participants in the SAFA (Spironolactone for Adult Female Acne) trial.

BACKGROUND: The use of decentralised clinical trials (which bring trials to patients through remote processes and technology versus central on-site visits) has been thought to be a potential solution to common recruitment and retention barriers. However, there is a lack of evidence to understand the experiences, needs and preferences of the public to inform trial methodologies that appeal to different populations. We report participant experiences of SAFA, a partially decentralised randomised clinical trial, to inform the methodology used in future dermatology trials that aim to appeal to women aged 18 and over. METHODS: Participants of the SAFA (Spironolactone for Adult Female Acne) trial were invited to take part in a qualitative semi-structured interview to explore their experience and perspectives of taking part in the trial. Questions focused on their experience of using decentralised methods to access and enrol in the trial (e.g. social media advertising), in addition to the decentralised trial visit and data collection methods used throughout. Interviews were conducted remotely, recorded, and transcribed. Data were analysed using reflexive thematic analysis. RESULTS: Twelve SAFA participants (all women, age range 22-36 years) were interviewed. Initially, participants were influenced to enrol by trusted online information, the feeling of validation the trial provided, and the convenience and flexibility offered by the decentralised methods and research staff made participants feel valued and enabled them to engage in the trial with minimal interference to existing commitments. SAFA participants were generally accepting of trial demands, such as the text-heavy paperwork and on-site visits for blood collection and highlighted several areas relevant for trial conduct going forwards including where decentralised methods may (and may not) be accepted and how trial accessibility and understanding could be improved. CONCLUSIONS: The study has shown that decentralised methods used by responsive and approachable staff were widely accepted in the SAFA trial. Interviewees found the methods adopted in the SAFA trial helped the trial to fit with their needs and promoted a sense of feeling valued that encouraged ongoing trial engagement. Decentralised methods should be considered favourably when designing a dermatology trial as they can potentially enhance both recruitment and retention. TRIAL REGISTRATION NUMBER: ISRCTN 12892056. Registered on October 15, 2018.

Systematic review of clinical practice guidelines for acne vulgaris published between January 2017 and July 2021.

Background: Acne is very common, can cause considerable negative impact on quality of life and there is increasing concern over the use of long courses of oral antibiotics for this condition. Objectives: (1) To critically appraise reporting in acne guidelines and compare this with previous systematic review of acne guidelines. (2) Examine acne treatment guidance on pre-specified acne treatments of interest and compare between acne guidelines. Methods: Searches for new or updated guidelines were carried out in MEDLINE, Embase, Google Scholar, LILACS from 1 January 2017 to 31 July 2021, supplemented by searching a guideline-specific depository and checking for updates to guidelines included in previous review. We included guidelines, consensus statements or care protocols on the medical treatment of acne vulgaris in adults and/or children and excluded those that focused on a single intervention or subgroup of acne, regional adaptations of guidelines or guidelines included in previous review. AGREE II checklist was applied to critically appraise reporting of guidelines. Results were synthesised narratively. Results: Of 807 abstracts identified nine guidelines were identified that were eligible for inclusion. All guidelines had AGREE II scores above average in at least one domain and reporting was substantially improved compared to the systematic review of acne carried out 5 years previously. There was consensus between guidelines on the key role of topical treatments as first-line acne treatment and most recommended continuing topical treatments as maintenance therapy. There was considerable variation between guidelines on classification of severity, indications for commencing oral antibiotics and on maximum duration of oral antibiotics. However, there was consensus on the need for co-prescription of a non-antibiotic topical treatment when using oral antibiotics. There were notable differences on recommendations regarding provision of information for patients on how to use topical treatments or how to mitigate against side effects. Conclusions: Substantial differences in classification of acne severity hampered comparisons between guidelines. Although development and reporting of guidelines has improved over the past 5 years, differences in key recommendations remain, possibly reflecting uncertainties in the underlying evidence base. Differences between guidelines could have substantial implications for prevalence of antibiotic prescribing for acne.

The Personalized Acne Treatment Tool - Recommendations to facilitate a patient-centered approach to acne management from the Personalizing Acne: Consensus of Experts.

Background: Acne, a commonly treated skin disease, requires patient-centered management due to its varying presentations, chronicity, and impact on health-related quality of life. Despite this, evidence-based clinical guidelines focus primarily on clinical severity of facial acne, omitting important patient- and disease-related factors, including ongoing management. Objectives: To generate recommendations to support patient-centered acne management, which incorporate priority and prognostic factors beyond conventional clinical severity, traditionally defined by grading the appearance and extent of visible lesions. Methods: The Personalizing Acne: Consensus of Experts consisted of 17 dermatologists who used a modified Delphi approach to reach consensus on statements regarding patient- and treatment-related factors pertaining to patient-centered acne management. Consensus was defined as ≥75% voting "agree" or "strongly agree." Results: Recommendations based on factors such as acne sequelae, location of acne, high burden of disease, and individual patient features were generated and incorporated into the Personalized Acne Treatment Tool. Limitations: Recommendations are based on expert opinion, which may differ from patients' perspectives. Regional variations in healthcare systems may not be represented. Conclusions: The Personalizing Acne: Consensus of Experts panel provided practical recommendations to facilitate individualized management of acne, based on patient features, which can be implemented to improve treatment outcomes, adherence, and patient satisfaction.

Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial.

OBJECTIVE: To assess the effectiveness of oral spironolactone for acne vulgaris in adult women. DESIGN: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. SETTING: Primary and secondary healthcare, and advertising in the community and on social media in England and Wales. PARTICIPANTS: Women (≥18 years) with facial acne for at least six months, judged to warrant oral antibiotics. INTERVENTIONS: Participants were randomly assigned (1:1) to either 50 mg/day spironolactone or matched placebo until week six, increasing to 100 mg/day spironolactone or placebo until week 24. Participants could continue using topical treatment. MAIN OUTCOME MEASURES: Primary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12 (range 0-30, where higher scores reflect improved QoL). Secondary outcomes were Acne-QoL at week 24, participant self-assessed improvement; investigator's global assessment (IGA) for treatment success; and adverse reactions. RESULTS: From 5 June 2019 to 31 August 2021, 1267 women were assessed for eligibility, 410 were randomly assigned to the intervention (n=201) or control group (n=209) and 342 were included in the primary analysis (n=176 in the intervention group and n=166 in the control group). Baseline mean age was 29.2 years (standard deviation 7.2), 28 (7%) of 389 were from ethnicities other than white, with 46% mild, 40% moderate, and 13% severe acne. Mean Acne-QoL symptom scores at baseline were 13.2 (standard deviation 4.9) and at week 12 were 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo (difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46), adjusted for baseline variables). Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo (difference 3.45 (95% confidence interval 2.16 to 4.75), adjusted). More participants in the spironolactone group reported acne improvement than in the placebo group: no significant difference was reported at week 12 (72% v 68%, odds ratio 1.16 (95% confidence interval 0.70 to 1.91)) but significant difference was noted at week 24 (82% v 63%, 2.72 (1.50 to 4.93)). Treatment success (IGA classified) at week 12 was 31 (19%) of 168 given spironolactone and nine (6%) of 160 given placebo (5.18 (2.18 to 12.28)). Adverse reactions were slightly more common in the spironolactone group with more headaches reported (20% v 12%; p=0.02). No serious adverse reactions were reported. CONCLUSIONS: Spironolactone improved outcomes compared with placebo, with greater differences at week 24 than week 12. Spironolactone is a useful alternative to oral antibiotics for women with acne. TRIAL REGISTRATION: ISRCTN12892056.

Real-World Case Studies Showing the Effective Use of Azelaic Acid in the Treatment, and During the Maintenance Phase, of Adult Female Acne Patients.

Acne Vulgaris is a chronic inflammatory skin disease, and one of the most prevalent inflammatory dermatoses among teenagers, affecting more than >95% of boys and 85% of girls. Adult female acne (AFA) is a subtype of acne, pragmatically defined as affecting women over the age of 25. The clinical presentation of AFA may be distinguished from adolescent acne according to some key clinical and psychosocial characteristics. The etiopathogenic factors and the chronic clinical course that are implicated in AFA make management complex and challenging. A frequent tendency to relapse makes the requirement for maintenance therapy highly likely. Therefore, AFA typically requires a specific, tailored therapeutic approach. This paper presents six challenging case studies that demonstrate the efficacy of azelaic acid gel (AZA) in adult female acne. The six cases use AZA as monotherapy, as part of a combination regimen at treatment initiation, or as maintenance treatment (which is frequently required in this adult population). The positive outcomes achieved in this case series demonstrate that AZA can be efficacious, result in excellent patient satisfaction in mild to moderate adult female acne, and can be effective as a maintenance therapy.

Adolescent acne vulgaris: current and emerging treatments.

Acne vulgaris is one of the commonest inflammatory skin diseases seen worldwide, affecting all ethnicities and races, with a peak prevalence between age 15 years and 20 years. The burden of this condition, and the resulting clinical and psychological sequelae, is substantial. The visual appearance of acne and its sequelae, including scarring and pigment changes, frequently results in psychological and social morbidity because of concerns about appearance. As understanding of the pathophysiology has evolved, approaches to achieving the optimal outcomes with effective treatment regimens continue to emerge. In the past few years, several novel therapeutics have been developed, including new agents aimed at reducing antimicrobial resistance and products with specific actions targeting retinoid receptors and androgen receptors. This Review considers the management approaches of an adolescent with acne vulgaris and reviews treatment options from the evidence base and international expert opinion. Approaches to selecting current treatments and novel and emerging treatment regimens are discussed.

Prevalence and Demographics of Truncal Involvement Among Acne Patients: Survey Data and a Review of the Literature.

Background: Truncal acne is frequently underdiagnosed despite affecting around half of those with facial acne. The objective was to provide an overview of the literature on the incidence of truncal acne according to age, gender, and acne severity. Methods: A narrative review of data from recent large surveys and a literature search in PubMed on the incidence of truncal acne across subgroups of age, gender, and acne severity. Results: The prevalence of truncal acne alone was low, ranging from <1% to 14%, but approximately 30 to 60 percent of individuals with facial acne also had truncal acne depending on the population. In an online survey in the United States of 2,000 respondents aged between 14 -29 years with self-reported active facial and/or truncal acne, the incidence of truncal acne was lower in the 14-20 years subgroup than in the 21-29 years subgroup (49% vs 54%). The incidence of truncal acne was similar in both males and females, while 46 percent of respondents with self-declared clear and mild acne indicated having truncal involvement compared to 60 percent of those with moderate or severe acne. Limitations: Online surveys have inherent limitations, such as self-reporting and potential confounders. Conclusion: Data suggests that patients with both facial and truncal involvement have earlier onset of acne and more severe acne. Additional adverse psychological impact may arise from having the impression that the disease is spreading and becoming more severe. Raising awareness of truncal acne prevalence and demographics could improve its clinical management to reduce the negative psychological impact.

Adapalene/benzoyl peroxide gel 0.3%/2.5% for acne vulgaris

Acne vulgaris is typically treated with a combination of a topical retinoid plus an antimicrobial agent, as recommended by national and international evidence-based guidelines around the globe. Adapalene, a synthetic topical retinoid, is available in two concentrations (0.1% and 0.3%) and in once-daily fixed-dose combinations with benzoyl peroxide (BPO) 2.5%. Adapalene 0.3%/BPO 2.5% is approved for use for moderate-to-severe acne with proven efficacy, good safety and tolerability across a spectrum of patient variables (different ages, genders, and skin types) and disease severity. While some patients experience issues with transient tolerability during retinoid and BPO therapy, it is our clinical experience that good patient education to set expectations and provide strategies to minimize irritation can overcome the majority of issues. This article reviews the data supporting the use of adapalene 0.3%/2.5% in practice, including the complementary mechanism of action of adapalene and BPO, clinical data from a range of settings, and key aspects of patient education.

Overcoming roadblocks in the development of vaccines for leishmaniasis.

INTRODUCTION: The leishmaniases represent a group of parasitic diseases caused by infection with one of several species of Leishmania parasites. Disease presentation varies because of differences in parasite and host genetics and may be influenced by additional factors such as host nutritional status or co-infection. Studies in experimental models of Leishmania infection, vaccination of companion animals and human epidemiological data suggest that many forms of leishmaniasis could be prevented by vaccination, but no vaccines are currently available for human use. AREAS COVERED: We describe some of the existing roadblocks to the development and implementation of an effective leishmaniasis vaccine, based on a review of recent literature found on PubMed, BioRxiv and MedRxiv. In addition to discussing scientific unknowns that hinder vaccine candidate identification and selection, we explore gaps in knowledge regarding the commercial and public health value propositions underpinning vaccine development and provide a route map for future research and advocacy. EXPERT OPINION: Despite significant progress, leishmaniasis vaccine development remains hindered by significant gaps in understanding that span the vaccine development pipeline. Increased coordination and adoption of a more holistic view to vaccine development will be required to ensure more rapid progress in the years ahead.

Gaps and recommendations for clinical management of truncal acne from the Personalising Acne: Consensus of Experts panel.

BACKGROUND: Truncal acne is common and burdensome for patients; however, there is paucity of evidence and guidance for the management of truncal acne. Currently, clinical practice guidelines provide very little guidance on the assessment or management of truncal acne. OBJECTIVES: To identify unmet needs in truncal acne and make recommendations to address clinical and management gaps using an international consensus. METHODS: The Personalising Acne: Consensus of Experts panel consisted of 13 dermatologists, who used a modified Delphi approach to reach a consensus on statements related to clinically relevant aspects of truncal acne evaluation and management. A consensus was defined as ≥75% of the panelists voting "agree" or "strongly agree." The voting was electronic and blinded. RESULTS: The panel identified gaps and made recommendations related to truncal acne identification, assessment, and grading; the evaluation of the impact on patients; and treatment goals and factors to be considered for its management. LIMITATIONS: The recommendations are based on expert opinion, in the absence of high-quality evidence. CONCLUSIONS: We highlighted addressing not just facial acne but also truncal acne during patient consultations. The recommendations made herein may help facilitate the care of patients who present with truncal acne, with or without facial acne.