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.

Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan.

Post-kala-azar dermal leishmaniasis (PKDL) is a chronic, stigmatizing skin condition occurring frequently after apparent clinical cure from visceral leishmaniasis. Given an urgent need for new treatments, we conducted a phase IIa safety and immunogenicity trial of ChAd63-KH vaccine in Sudanese patients with persistent PKDL. LEISH2a (ClinicalTrials.gov: NCT02894008) was an open-label three-phase clinical trial involving sixteen adult and eight adolescent patients with persistent PKDL (median duration, 30 months; range, 6-180 months). Patients received a single intramuscular vaccination of 1 × 1010 viral particles (v.p.; adults only) or 7.5 × 1010 v.p. (adults and adolescents), with primary (safety) and secondary (clinical response and immunogenicity) endpoints evaluated over 42-120 days follow-up. AmBisome was provided to patients with significant remaining disease at their last visit. ChAd63-KH vaccine showed minimal adverse reactions in PKDL patients and induced potent innate and cell-mediated immune responses measured by whole-blood transcriptomics and ELISpot. 7/23 patients (30.4%) monitored to study completion showed >90% clinical improvement, and 5/23 (21.7%) showed partial improvement. A logistic regression model applied to blood transcriptomic data identified immune modules predictive of patients with >90% clinical improvement. A randomized controlled trial to determine whether these clinical responses were vaccine-related and whether ChAd63-KH vaccine has clinical utility is underway.

Concerns, Expectations, and Management Gaps Relating to Acne and Associated Scarring Identified from Survey Data.

INTRODUCTION: Our objective was to identify concerns, burden of disease, education gaps, and expectations of acne/acne scarring respondents and investigate acne/acne scarring related burden. Also, to consider perception of acne/acne scarring and additional education needs through responses from the general population. METHODS: One online survey from 1000 respondents aged 14–26 years old who currently had moderate to severe acne and/or acne scarring (AcnePop) and one from 2000 nationally representative USA respondents aged ≥14 years old [general population (GenPop)]. RESULTS: Among the AcnePop, 26% had never consulted a healthcare professional and 36% never received a prescription for acne/acne scarring. Of those who had seen a medical professional, 72% consulted a dermatologist, 45% a primary care physician, and 23% a therapist/psychiatrist. The vast majority (94%) were dissatisfied with information they received from the healthcare provider. Topics they desired more information on included available treatment options (46%), how different skin types are affected by acne (44%), acne triggers (44%), and their acne severity (43%). Of GenPop (n=781) who had given unsolicited advice to people with acne, the most common suggestions were to see a doctor (47%), change their hygiene habits (39%), or change their diet (37%). CONCLUSION: AcnePop are often dissatisfied with the information they receive from healthcare providers and more comprehensive information should be provided to help them understand their condition and available treatment options. J Drugs Dermatol. 2021;20(6):600-606. doi:10.36849/JDD.5920.

Navigating the landscape of core outcome set development in dermatology.

The development of core outcome sets (COSs; ie, a minimum set of core outcomes that should be measured and reported in all trials or in clinical practice for a specific condition) in dermatology is increasing in pace. A total of 44 dermatology-related COS projects have been registered in the online Core Outcome Measures in Effectiveness Trials database (http://www.comet-initiative.org/studies/search) and include studies on 26 different skin diseases. With the increasing number of COSs in dermatology, care is needed to ensure the delivery of high-quality COSs that meet quality standards when using state-of-the-art methods. In 2015, the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) was established. CS-COUSIN is an international, multidisciplinary working group aiming to improve the development and implementation of COSs in dermatology. CS-COUSIN has developed guidance on how to develop high-quality COSs for skin diseases and supports dermatology-specific COS initiatives. Currently, 17 COS development groups are affiliated with CS-COUSIN and following standardized COS development processes. To ensure successful uptake of COSs in dermatology, researchers, clinicians, systematic reviewers, guideline developers, and other stakeholders should use existing COSs in their work.

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.

Light therapies for acne.

BACKGROUND: Acne vulgaris is a very common skin problem that presents with blackheads, whiteheads, and inflamed spots. It frequently results in physical scarring and may cause psychological distress. The use of oral and topical treatments can be limited in some people due to ineffectiveness, inconvenience, poor tolerability or side-effects. Some studies have suggested promising results for light therapies. OBJECTIVES: To explore the effects of light treatment of different wavelengths for acne. SEARCH METHODS: We searched the following databases up to September 2015: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We searched ISI Web of Science and Dissertation Abstracts International (from inception). We also searched five trials registers, and grey literature sources. We checked the reference lists of studies and reviews and consulted study authors and other experts in the field to identify further references to relevant randomised controlled trials (RCTs). We updated these searches in July 2016 but these results have not yet been incorporated into the review. SELECTION CRITERIA: We included RCTs of light for treatment of acne vulgaris, regardless of language or publication status. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 71 studies, randomising a total of 4211 participants.Most studies were small (median 31 participants) and included participants with mild to moderate acne of both sexes and with a mean age of 20 to 30 years. Light interventions differed greatly in wavelength, dose, active substances used in photodynamic therapy (PDT), and comparator interventions (most commonly no treatment, placebo, another light intervention, or various topical treatments). Numbers of light sessions varied from one to 112 (most commonly two to four). Frequency of application varied from twice daily to once monthly.Selection and performance bias were unclear in the majority of studies. Detection bias was unclear for participant-assessed outcomes and low for investigator-assessed outcomes in the majority of studies. Attrition and reporting bias were low in over half of the studies and unclear or high in the rest. Two thirds of studies were industry-sponsored; study authors either reported conflict of interest, or such information was not declared, so we judged the risk of bias as unclear.Comparisons of most interventions for our first primary outcome 'Participant's global assessment of improvement' were not possible due to the variation in the interventions and the way the studies' outcomes were measured. We did not combine the effect estimates but rated the quality of the evidence as very low for the comparison of light therapies, including PDT to placebo, no treatment, topical treatment or other comparators for this outcome. One study which included 266 participants with moderate to severe acne showed little or no difference in effectiveness for this outcome between 20% aminolevulinic acid (ALA)-PDT (activated by blue light) versus vehicle plus blue light (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.72 to 1.04, low-quality evidence). A study (n = 180) of a comparison of ALA-PDT (activated by red light) concentrations showed 20% ALA was no more effective than 15% (RR 1.05, 95% CI 0.96 to 1.15) but better than 10% ALA (RR 1.22, 95% CI 1.05 to 1.42) and 5% ALA (RR 1.47, 95% CI 1.19 to 1.81). The number needed to treat for an additional beneficial outcome (NNTB) was 6 (95% CI 3 to 19) and 4 (95% CI 2 to 6) for the comparison of 20% ALA with 10% and 5% ALA, respectively.For our second primary outcome 'Investigator-assessed changes in lesion counts', we combined three RCTs, with 360 participants with moderate to severe acne and found methyl aminolevulinate (MAL) PDT (activated by red light) was no different to placebo cream plus red light with regard to change in inflamed lesions (ILs) (mean difference (MD) -2.85, 95% CI -7.51 to 1.81), percentage change in ILs (MD -10.09, 95% CI -20.25 to 0.06), change in non-inflamed lesions (NILs) (MD -2.01, 95% CI -7.07 to 3.05), or in percentage change in NILs (MD -8.09, 95% CI -21.51 to 5.32). We assessed the evidence as moderate quality for these outcomes meaning that there is little or no clinical difference between these two interventions for lesion counts.Studies comparing the effects of other interventions were inconsistent or had small samples and high risk of bias. We performed only narrative synthesis for the results of the remaining trials, due to great variation in many aspects of the studies, poor reporting, and failure to obtain necessary data. Several studies compared yellow light to placebo or no treatment, infrared light to no treatment, gold microparticle suspension to vehicle, and clindamycin/benzoyl peroxide combined with pulsed dye laser to clindamycin/benzoyl peroxide alone. There were also several other studies comparing MAL-PDT to light-only treatment, to adapalene and in combination with long-pulsed dye laser to long-pulsed dye laser alone. None of these showed any clinically significant effects.Our third primary outcome was 'Investigator-assessed severe adverse effects'. Most studies reported adverse effects, but not adequately with scarring reported as absent, and blistering reported only in studies on intense pulsed light, infrared light and photodynamic therapies. We rated the quality of the evidence as very low, meaning we were uncertain of the adverse effects of the light therapies.Although our primary endpoint was long-term outcomes, less than half of the studies performed assessments later than eight weeks after final treatment. Only a few studies assessed outcomes at more than three months after final treatment, and longer-term assessments are mostly not covered in this review. AUTHORS' CONCLUSIONS: High-quality evidence on the use of light therapies for people with acne is lacking. There is low certainty of the usefulness of MAL-PDT (red light) or ALA-PDT (blue light) as standard therapies for people with moderate to severe acne.Carefully planned studies, using standardised outcome measures, comparing the effectiveness of common acne treatments with light therapies would be welcomed, together with adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.

Interventions for acne scars.

BACKGROUND: Acne scarring is a frequent complication of acne and resulting scars may negatively impact on an affected person's psychosocial and physical well-being. Although a wide range of interventions have been proposed, there is a lack of high-quality evidence on treatments for acne scars to better inform patients and their healthcare providers about the most effective and safe methods of managing this condition. This review aimed to examine treatments for atrophic and hypertrophic acne scars, but we have concentrated on facial atrophic scarring. OBJECTIVES: To assess the effects of interventions for treating acne scars. SEARCH METHODS: We searched the following databases up to November 2015: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2015, Issue 10), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched five trials registers, and checked the reference lists of included studies and relevant reviews for further references to randomised controlled trials. SELECTION CRITERIA: We include randomised controlled trials (RCTs) which allocated participants (whether split-face or parallel arms) to any active intervention (or a combination) for treating acne scars. We excluded studies dealing only or mostly with keloid scars. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data from each of the studies included in this review and evaluated the risks of bias. We resolved disagreements by discussion and arbitration supported by a method expert as required. Our primary outcomes were participant-reported scar improvement and any adverse effects serious enough to cause participants to withdraw from the study. MAIN RESULTS: We included 24 trials with 789 adult participants aged 18 years or older. Twenty trials enrolled men and women, three trials enrolled only women and one trial enrolled only men. We judged eight studies to be at low risk of bias for both sequence generation and allocation concealment. With regard to blinding we judged 17 studies to be at high risk of performance bias, because the participants and dermatologists were not blinded to the treatments administered or received; however, we judged all 24 trials to be at a low risk of detection bias for outcome assessment. We evaluated 14 comparisons of seven interventions and four combinations of interventions. Nine studies provided no usable data on our outcomes and did not contribute further to this review's results.For our outcome 'Participant-reported scar improvement' in one study fractional laser was more effective in producing scar improvement than non-fractional non-ablative laser at week 24 (risk ratio (RR) 4.00, 95% confidence interval (CI) 1.25 to 12.84; n = 64; very low-quality evidence); fractional laser showed comparable scar improvement to fractional radiofrequency in one study at week eight (RR 0.78, 95% CI 0.36 to 1.68; n = 40; very low-quality evidence) and was comparable to combined chemical peeling with skin needling in a different study at week 48 (RR 1.00, 95% CI 0.60 to 1.67; n = 26; very low-quality evidence). In a further study chemical peeling showed comparable scar improvement to combined chemical peeling with skin needling at week 32 (RR 1.24, 95% CI 0.87 to 1.75; n = 20; very low-quality evidence). Chemical peeling in one study showed comparable scar improvement to skin needling at week four (RR 1.13, 95% CI 0.69 to 1.83; n = 27; very low-quality evidence). In another study, injectable fillers provided better scar improvement compared to placebo at week 24 (RR 1.84, 95% CI 1.31 to 2.59; n = 147 moderate-quality evidence).For our outcome 'Serious adverse effects' in one study chemical peeling was not tolerable in 7/43 (16%) participants (RR 5.45, 95% CI 0.33 to 90.14; n = 58; very low-quality evidence).For our secondary outcome 'Participant-reported short-term adverse events', all participants reported pain in the following studies: in one study comparing fractional laser to non-fractional non-ablative laser (RR 1.00, 95% CI 0.94 to 1.06; n = 64; very low-quality evidence); in another study comparing fractional laser to combined peeling plus needling (RR 1.00, 95% CI 0.86 to 1.16; n = 25; very low-quality evidence); in a study comparing chemical peeling plus needling to chemical peeling (RR 1.00, 95% CI 0.83 to 1.20; n = 20; very low-quality evidence); in a study comparing chemical peeling to skin needling (RR 1.00, 95% CI 0.87 to 1.15; n = 27; very low-quality evidence); and also in a study comparing injectable filler and placebo (RR 1.03, 95% CI 0.10 to 11.10; n = 147; low-quality evidence).For our outcome 'Investigator-assessed short-term adverse events', fractional laser (6/32) was associated with a reduced risk of hyperpigmentation than non-fractional non-ablative laser (10/32) in one study (RR 0.60, 95% CI 0.25 to 1.45; n = 64; very low-quality evidence); chemical peeling was associated with increased risk of hyperpigmentation (6/12) compared to skin needling (0/15) in one study (RR 16.00, 95% CI 0.99 to 258.36; n = 27; low-quality evidence). There was no difference in the reported adverse events with injectable filler (17/97) compared to placebo (13/50) (RR 0.67, 95% CI 0.36 to 1.27; n = 147; low-quality evidence). AUTHORS' CONCLUSIONS: There is a lack of high-quality evidence about the effects of different interventions for treating acne scars because of poor methodology, underpowered studies, lack of standardised improvement assessments, and different baseline variables.There is moderate-quality evidence that injectable filler might be effective for treating atrophic acne scars; however, no studies have assessed long-term effects, the longest follow-up being 48 weeks in one study only. Other studies included active comparators, but in the absence of studies that establish efficacy compared to placebo or sham interventions, it is possible that finding no evidence of difference between two active treatments could mean that neither approach works. The results of this review do not provide support for the first-line use of any intervention in the treatment of acne scars.Although our aim was to identify important gaps for further primary research, it might be that placebo and or sham trials are needed to establish whether any of the active treatments produce meaningful patient benefits over the long term.

Over 25 Years of Clinical Experience With Ivermectin: An Overview of Safety for an Increasing Number of Indications.

Although the broad-spectrum anti-parasitic effects of the avermectin derivative ivermectin are well documented, its anti-inflammatory activity has only recently been demonstrated. For over 25 years, ivermectin has been used to treat parasitic infections in mammals, with a good safety profile that may be attributed to its high affinity to invertebrate neuronal ion channels and its inability to cross the blood-brain barrier in humans and other mammals. Numerous studies report low rates of adverse events, as an oral treatment for parasitic infections, scabies and head lice. Ivermectin has been used off-label to treat diseases associated with Demodex mites, such as blepharitis and demodicidosis. New evidence has linked Demodex mites to rosacea, a chronic inflammatory disease. Ivermectin has recently received FDA and EU approval for the treatment of adult patients with inflammatory lesions of rosacea, a disease in which this agent has been shown to be well tolerated. After more than 25 years of use, ivermectin continues to provide a high margin of safety for a growing number of indications based on its anti-parasitic and anti-inflammatory activities.

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.

What's New After NICE Acne Guidelines.

INTRODUCTION: Acne remains one of the most common inflammatory dermatoses seen worldwide. There are significant challenges when managing acne relating to a variety of factors, including (1) lack of consensus on the use of the numerous available grading systems and outcome measures, (2) appreciation of the numerous areas that relate to severity, (3) the chronic nature of acne which requires a longitudinal approach to management (including both facial and truncal disease), and (4) the need to target acne early to avoid physical and psychosocial scarring. Consideration of these aspects when managing acne should result in improved outcomes. Acne guidelines review the available evidence based on robust clinical trials and are usually supplemented with some expert opinion when evidence is not available. METHODS: In this paper, the UK Acne Working Group reflects on the latest National Institute for Health and Care Excellence (NICE) acne guidelines with a goal of providing additional practical insights. CONCLUSION: The group have identified areas where new evidence has now become available since the formulation of the NICE acne guidelines. This publication considers newly approved acne medications in the UK, guidance on assessing acne severity, approaches to managing truncal acne, acne sequelae, and adult female acne with hormonal therapies.

The National Institute for Health and Care Excellence (NICE) produced acne guidelines in June 2021 for clinicians and patients. New evidence and information on practical aspects of acne management have emerged since this time. A panel of clinicians with expertise in acne discuss herein some areas of interest that may support acne management, some of which could be considered in a second iteration of NICE acne guidelines. These areas include how to assess acne, the medical approach to truncal acne, how clinicians may manage the long-lasting acne sequelae of scarring and darkly pigmented spots, and the use of medical hormonal therapies for women (such as birth control pills) to manage acne that may have a causative contribution of hormone imbalances.

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.

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 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.

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.

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.

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.