Search

Acne-focused dermatology expert groups have consistently recommended that most patients with acne be treated with a combination of topical retinoid and antimicrobial therapy. This is based on clinical data as well as evidence that these drug classes have different and complementary mechanisms of action that target multiple aspects of acne’s complex pathophysiology. Recent evidence-based guidelines for acne, including those from the American Academy of Dermatology (AAD) and the European Dermatology Forum (EDF), have agreed that retinoids have an essential role in this widespread disease. The AAD states “retinoids are the core of topical therapy for acne because they are comedolytic, resolve the precursor microcomedone lesion, and are anti-inflammatory;” further, they “allow for maintenance of clearance.” Despite uniform recommendation for use of topical retinoids, a recent study of prescribing practices from 2012 to 2014 indicated that dermatologists prescribed retinoids just 58.8% of the time while non-dermatologists prescribed them for only 32.4% of cases. In this article, we review the reasons supporting retinoids as the mainstay of acne therapy and discuss some of the perceived barriers that may be limiting use of this important drug class. Further, we discuss how and when titrating retinoid concentrations may be utilized in clinical practice. Funding: Galderma International.

Background Sunscreens are known to protect from sun damage; however, their effects on the reversal of photodamage have been minimally investigated. Objective The aim of the prospective study was to evaluate the efficacy of a facial sun protection factor (SPF) 30 formulation for the improvement of photodamage during a 1-year use. Methods Thirty-two subjects applied a broad spectrum photostable sunscreen (SPF 30) for 52 weeks to the entire face. Assessments were conducted through dermatologist evaluations and subjects' self-assessment at baseline and then at Weeks 12, 24, 36, and 52. Results Clinical evaluations showed that all photoaging parameters improved significantly from baseline as early as Week 12 and the amelioration continued until Week 52. Skin texture, clarity, and mottled and discrete pigmentation were the most improved parameters by the end of the study (40% to 52% improvement from baseline), with 100% of subjects showing improvement in skin clarity and texture. Conclusion The daily use of a facial broad-spectrum photostable sunscreen may visibly reverse the signs of existing photodamage, in addition to preventing additional sun damage.

Mild and moisturizing cleanser technologies, and the science underpinning them, have progressed significantly over the past decade. This includes introduction of amino-acid based milder surfactants into the cleansing arena, a deeper understanding of the roles of stratum corneum lipids and proteins in their interaction with cleanser surfactants, the role of pH in skin cleansing, and the development of improved methodologies for predicting skin irritation and drying potential of cleansers. In this paper, the recent advances in these areas as well as newer technologies are reviewed, and the future directions are outlined. J Drugs Dermatol. 2019;18(1 Suppl):s80-88

There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris.In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations.Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred.Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other tetracycline options, which may lead to less selective pressure on enteric Gram-negative bacteria, resulting in less disruption of commensal organisms and less potential for antibiotic resistance.pemJ Drugs Dermatol. 2018;17(3):333-338./em/p.

Summary Background The nuclear factor-κB (NF-κB) pathway is a key mediator of inflammation; however, few studies have examined the direct effects of NF-κB inhibition on the skin. Objectives To investigate NF-κB activity in cultured human fibroblasts and to investigate the effects of 4-hexyl-1,3-phenylenediol (an NF-κB inhibitor) on elastin and collagen gene expression in vitro and on the clinical appearance of photodamaged skin. Methods The amount and activity of NF-κB in human fibroblasts obtained from donors (17–78 years old) was measured after transfection with a NF-κB reporter and a luciferase promoter system. The expression of extracellular matrix (ECM) genes was determined using quantitative polymerase chain reaction. Women with moderate skin photodamage were randomized to daily treatment with a topical lotion containing 4-hexyl-1,3-phenylenediol (n = 30) or vehicle (n = 29) for 8 weeks, with clinical assessments at baseline and weeks 2, 4 and 8. Results Fibroblasts obtained from donors older than 50 years had higher NF-κB activity compared with cells from younger donors; inhibition of the NF-κB pathway with 4-hexyl-1,3-phenylenediol enhanced the expression of ECM genes. In women, treatment for 8 weeks with 4-hexyl-1,3-phenylenediol significantly improved crow's feet fine lines, cheek wrinkles, age spots, mottled pigmentation and radiance compared with both the vehicle and baseline. Furthermore, treatment with 4-hexyl-1,3-phenylenediol resulted in a twofold greater clinical improvement in overall photodamage compared with the vehicle group. Conclusions Inhibition of the proinflammatory NF-κB pathway resulted in increased expression of ECM proteins in vitro and significant clinical improvement in photodamaged skin.

Acne has long been understood to have a complex physiological basis involving several main factors: hormonally-stimulated sebum production, abnormal keratinization of the pilosebaceous duct, and an inflammatory immune response to Propionibacterium acnes. Recent studies at the molecular and cellular level have begun clarifying how all of these factors interact, and the role of the innate immune system is better appreciated. Inflammation has been demonstrated in all acne lesions - the preclinical microcomedo, comedones, inflammatory lesions, 'post-inflammatory' erythema or hyperpigmentation, and scarring. Inflammation localized to the pilosebaceous unit can be considered the defining feature of acne and should be addressed via multiple therapeutic pathways. Clinicians tend to think oral antibiotics should be used to 'calm' inflammatory acne, but there is good evidence showing that topical retinoids also have anti-inflammatory properties as a class effect. For best therapeutic outcomes, most patients with acne should be treated first line with a topical retinoid plus an antimicrobial agent, as has been demonstrated in thousands of patients involved in clinical trials and recommended by the Global Alliance to Improve Outcomes in Acne for more than a decade. Moving away from reliance on antibiotic therapy for acne is particularly important in an era of worsening antimicrobial resistance and worldwide calls to reduce antibiotic use. Improved understanding about the role of P. acnes and the innate immune system in acne should help clinicians in designing efficacious treatment strategies.

A supplement article recently published in the Journal of the European Academy of Dermatology and Venereology by Dréno et al., members of the Global Alliance to Improve Outcomes in Acne group, summarized the data for the emerging concept that inflammation in general and the innate immune system specifically play a central role in the pathogenesis of acne. This review, entitled "Understanding innate immunity and inflammation in acne: implications for management", also discusses the impact of different treatment options on the innate immune response and inflammation. The aim of the present summary is to provide a synopsis of the key points made in the paper, from the members of the Global Alliance, as relevant to the main article within this supplement: "Recent advances in the use of adapalene 0.1%/benzoyl peroxide 2.5% to treat acne patients with moderate to severe acne".

Background A high-fat meal is needed for optimal absorption of isotretinoin. A new formulation of isotretinoin, which enhances absorption of isotretinoin in the absence of dietary fat, has recently been approved by the Food and Drug Administration (FDA). Objective We sought to compare the pharmacokinetic profiles of a new formulation of isotretinoin (isotretinoin-Lidose) with the innovator isotretinoin formulation. Methods This study was an open-label, single-dose, randomized, 4-treatment, crossover comparative trial between a new and innovator formulation of isotretinoin in the fasting and fed states. Results Both formulations were bioequivalent under fed conditions. As expected in a fasting state, absorption of both formulations was reduced. A considerable difference between the 2 drugs occurred under fasted conditions–there was a marked improvement in overall bioavailability of the isotretinoin-Lidose formulation. Mean plasma levels of the isotretinoin-Lidose formulation during fasting reached 66.8% of that observed with a fatty meal, and those of the isotretinoin formulation only reached 39.6% of that observed with a fatty meal. Limitations Only the FDA-stipulated standard high-fat, high-calorie meal of 50-g fat was studied in the fed state. Conclusion Isotretinoin-Lidose formulation is bioequivalent to the innovator formulation under fed conditions with regard to its pharmacokinetic profile but delivers twice as much isotretinoin and 4-oxo-isotretinoin when administered after an overnight fast.

Background Acne is a chronic dermatological disease predominantly afflicting young adults and is often associated with the development of scars. Acne scarring is usually avoidable when acne is managed early and effectively. However, acne patients often fail to seek early treatment. New and innovative tools to raise awareness are needed. Objective This study presents the development and assessment of a tool aiming to assess the risk of atrophic acne scars. Methods A systematic literature review of clinical risk factors for acne scars, a Delphi-like survey of dermatological experts in acne and secondary data analysis, were conducted to produce an evidence-based risk assessment tool. The tool was assessed both with a sample of young adults with and without scars and was assessed via a database cross-validation. Results A self-administered tool for risk assessment of developing atrophic acne scars in young adults was developed. It is a readily comprehensible and practical tool for population education and for use in medical practices. It comprises of four risk factors: worst ever severity of acne, duration of acne, family history of atrophic acne scars and lesion manipulation behaviours. It provides a dichotomous outcome: lower vs. higher risk of developing scars, thereby categorizing nearly two-thirds of the population correctly, with sensitivity of 82% and specificity of 43%. Conclusion The present tool was developed as a response to current challenges in acne scar prevention. A potential benefit is to encourage those at risk to self-identify and to seek active intervention of their acne. In clinical practice, we expect this tool may help clinicians identify patients at risk of atrophic acne scarring and underscore their requirement for rapid and effective acne treatment.

Background Acne fulminans (AF) is a severe variant of inflammatory acne. It typically manifests as an explosive worsening and ulceration of skin lesions, and can be associated with systemic symptoms. However, there is a paucity of evidence-based information and no clear guidelines concerning the classification and treatment of AF. Objective To better define the spectrum of AF and its variants, devise optimal therapeutic approaches, and identify areas of future research. Methods A panel of physicians with expertise in severe acne vulgaris was convened after a comprehensive literature review of severe acne variants. Priority topics were reviewed and presented by each panelist at a 5-hour conference. Following review of the audiotape and scribed notes from the conference, surveys were utilized to address points of controversy and to clarify consensus recommendations. Results Appropriate clinical case presentations and consensus survey questions were utilized to create final recommendations based on both the literature and the expert consensus. Limitations Limited evidenced-based data and prospective studies in the literature concerning the treatment of AF is available. Conclusion These guidelines better characterize AF and provide health care practitioners approaches to the classification, treatment, and prevention of AF and its variants.

The central role of inflammation in acne is now more clearly understood. Adapalene, a third-generation topical retinoid, down-regulates toll-like receptor 2 expression and inhibits activator protein-1 activity. In a fixed-dose combination, adapalene and benzoyl peroxide (BPO) act synergistically on inflammatory patterns through regulation of innate immunity. In addition to reducing inflammatory and non-inflammatory lesions, adapalene/BPO helps prevent lesion and microcomedone formation. The combination of a topical retinoid and antimicrobial agent remains the preferred approach for almost all patients with acne. In cases of more severe disease, there is a clinical benefit in combining adapalene/BPO with an oral antibiotic for 12 weeks. Most recently, adapalene/BPO plus doxycycline 200 mg was found to be highly effective when compared with isotretinoin in the treatment of patients with severe acne with nodules. Long-term maintenance therapy is needed for most patients. Retinoids are the preferred agents, with BPO added in patients with more severe disease if needed. Adapalene is anticomedogenic, reduces comedones and has anti-inflammatory properties, while BPO is a unique antimicrobial agent not shown to induce microbial resistance after more than 50 years of use. Maintenance therapy for 6 months with adapalene/BPO prevents relapse among patients with severe acne and continues to reduce disease symptoms.

Background Until now, nonablative fractional treatments could only be delivered in an office setting by trained professionals. Objective The goal of this work was to perform clinical testing of a nonablative fractional laser device designed for home-use. Methods This multicenter trial consisted of two clinical studies with slightly varying treatment protocols in which subjects performed at-home treatments of periorbital wrinkles using a handheld nonablative fractional laser. Both studies included an active treatment phase (daily treatments) and a maintenance phase (twice-weekly treatments). In all, 36 subjects were followed up for as long as 5 months after completion of the maintenance phase and 90 subjects were followed up until the completion of the maintenance phase. Evaluations included in-person investigator assessment, independent blinded review of high-resolution images using the Fitzpatrick Wrinkle Scale, and subject self-assessment. Results All 124 subjects who completed the study were able to use the device following written instructions for use. Treatments were well tolerated with good protocol compliance. Independent blinded evaluations by a panel of physicians showed Fitzpatrick Wrinkle Scale score improvement by one or more grades in 90% of subjects at the completion of the active phase and in 79% of subjects at the completion of the maintenance phase. The most prevalent side effect was transient posttreatment erythema. Limitations Lack of a control group and single-blinded study groups were limitations. Conclusion Safety testing with self-applications by users demonstrated the utility of the device for home use. Independent blinded review of clinical images confirmed the device's proficiency for improving periorbital wrinkles.

Background There are multiple global scales for acne severity grading but no singular standard. Objective Our objective was to determine the essential clinical components (content items) and features (property-related items) for an acne global grading scale for use in research and clinical practice using an iterative method, the Delphi process. Methods Ten acne experts were invited to participate in a Web-based Delphi survey comprising 3 iterative rounds of questions. Results In round 1, the experts identified the following clinical components (primary acne lesions, number of lesions, extent, regional involvement, secondary lesions, and patient experiences) and features (clinimetric properties, ease of use, categorization of severity based on photographs or text, and acceptance by all stakeholders). In round 2, consensus for inclusion in the scale was established for primary lesions, number, sites, and extent; as well as clinimetric properties and ease of use. In round 3, consensus for inclusion was further established for categorization and acceptance. Patient experiences were excluded and no consensus was achieved for secondary lesions. Limitations The Delphi panel consisted solely of the United States (U.S.)–based acne experts. Conclusion Using an established method for achieving consensus, experts in acne vulgaris concluded that an ideal acne global grading scale would comprise the essential clinical components of primary acne lesions, their quantity, extent, and facial and extrafacial sites of involvement; with features of clinimetric properties, categorization, efficiency, and acceptance.

Facial hyperpigmented disorders are a common complaint in the adult population of all races. First-line topical treatments are usually hydroquinone or topical retinoids, which can cause irritant reactions. The need for better tolerated, yet effective, skin lightening agents that could be utilized by a wider population has led to the investigation of several potential botanical/natural compounds. There are currently many topical cosmetic formulations claiming skin depigmenting effects. A few of the ingredients (e.g. soy) are supported not only by in vitro results but also by a body of controlled clinical efficacy studies; other ingredients, instead, are backed mostly by in vitro data and a few small uncontrolled clinical studies. In this review, we describe the most common natural ingredients used for skin depigmentation and their major published studies: soy, licorice extracts, kojic acid, arbutin, niacinamide, N-acetylglucosamine, COFFEEBERRY™ and green tea.

Background Post-inflammatory hyperpigmentation (PIH) is a common occurrence in patients with acne vulgaris, particularly in those with skin of colour. Aims A previous study has demonstrated the benefit of tretinoin (retinoic acid) in the treatment of PIH; however, there is currently no standard protocol to evaluate change in PIH following treatment. Based on these findings, we performed a pilot, exploratory, blinded, intraindividual-controlled methodology study that consisted of a photographic assessment protocol with facial mapping. Materials and methods The study was based on a secondary analysis of a phase 4, community-based trial of 544 acne patients who were treated with tretinoin gel microsphere 0.04% or 0.1%. Only patients with Fitzpatrick types III–V (skin of colour) were included in the study; subjects with Fitzpatrick skin type VI were excluded because the photographic assessment did not allow for proper evaluation. Results Despite the small number of subjects evaluated (n = 25), the results revealed consistent assessment of improvement in PIH between two independent graders (weighted κ = 0.84). Conclusion Further study with a larger population is recommended to validate the accuracy of this method.

Background Hyperpigmentation disorders are common and diverse conditions that may require treatment for medical and/or cosmetic reasons. Hyperpigmented lesions can reduce patients’ quality of life, self-perception, and social and vocational functioning. The most commonly used treatments for hyperpigmentation include topical agents, such as hydroquinone, retinoids and azelaic acid. Objectives Current topical treatments have significant limitations; they often do not produce adequate results and may be limited by adverse effects, such as dermatitis. Soy and soy-based products have demonstrated a wide range of potential benefits for health and nutrition, including a range of dermatological effects. Methods Research from the last decade has identified multiple mechanisms by which soy-derived products may affect skin pigmentation, as well as photodamage and photoaging, overall skin health, and even the risk for and progression of skin cancer. Results Preclinical evidence has demonstrated that soy-derived serine protease inhibitors affect skin pigmentation by inhibiting protease-activated receptor-2-mediated phagocytosis of melanosomes by keratinocytes. Conclusion Soy-based products containing these serine protease inhibitors may represent a new therapeutic option for dermatological treatment. Indeed, recent evidence from randomized clinical studies supports the safe and effective use of soy products for the treatment of hyperpigmentation.

Acne is a common chronic disease that typically requires prolonged treatment. Several small studies conducted over the past few years suggest that adherence to acne medications is often poor. In addition, data regarding the factors that positively or negatively impact adherence in patients with acne are sparse. This study utilized a simple, validated questionnaire (ECOB, Elaboration d'un outil d'evaluation de l'observance des traitements medicamenteux) to assess the risk of poor adherence in a large worldwide cohort of acne patients (n = 3339) from three major geographic regions [the Americas (n = 952), Europe (n = 1196), and Asia (n = 1191). In addition, information about patient and treatment characteristics was collected to identify factors that correlated with adherence. Overall, there was a poor adherence rate of 50% in this study; this varied by region, with significantly worse adherence in Europe versus Asia and America (poor adherence rates of 58%, 48%, and 43%, respectively, P < 0.0001). To provide insight into factors that affect medication-taking behavior in acne, adherence was analyzed by the type of treatment (a combination of topical and systemic, topical only, oral isotretinoin). Among patients taking a combination of both systemic and topical therapy, 60% (n = 944) of patients had poor adherence to at least one treatment as defined in the study protocol. In this group, there was a higher proportion of patients who had poor adherence to systemic treatment versus topical treatment (54% vs. 44%, respectively). Among patients treated with topical therapy only, poor adherence occurred in 40% (n = 356) of cases. A total of 46% (n = 325) of patients using oral isotretinoin therapy had poor adherence. Multivariate analysis showed that poor adherence was independently correlated with young age (most strongly with

The human axillae have a characteristic odour that is comprised of or generated from a mixture of C6–C11 normal, branched, hydroxy- and unsaturated acids (and other compounds). We used ethyl esters of one of these acids and a palette of fragrance compounds (tested individually) to evaluate the effectiveness of these chemicals to reduce the overall olfactory impact of a model of human stress-related odour (SRO) by cross-adaptation (adaptation to one odorant can reduce sensitivity to other odorants). Sensory volunteers provided hedonic and intensity ratings of the SRO and of each of the potential cross-adapting agents prior to 2.5 min of induced olfactory adaptation to each agent. Across adaptation, possible cross-adaptation was evaluated by intermittent evaluations of the perceived intensity of the SRO. We determined that some potential cross-adapting agents did reduce the impact of the SRO; however, the same chemicals were not necessarily effective for male and female SRO. Indeed, the list of effective chemicals depended upon the gender of the donor of the SRO and the gender of the sensory volunteer, suggesting a gender-specific response to both the SRO-stimuli used and the fragrance chemicals used to cross-adapt it. Copyright © 2009 John Wiley & Sons, Ltd.

Background Medical therapies for hidradenitis suppurativa (HS) are often ineffective. Tumor necrosis factor-α inhibitors may be a potential treatment for patients with moderate to severe HS. Objectives We sought to evaluate the safety and efficacy of etanercept for patients with severe HS. Methods We conducted a phase II clinical trial of etanercept (50 mg/wk subcutaneously) in patients with moderate to severe HS. Efficacy was measured using a Physician Global Assessment and several secondary physician- and patient-reported outcome measures. Responders were classified as those achieving at least a 50% reduction on the Physician Global Assessment score at week 12 compared with baseline. Results Only 3 of the 15 patients who entered the study were classified as responders (response rate of 20%; 95% confidence interval: 4.3-48.1) based on the intention-to-treat analysis. Dermatology Life Quality Index scores improved slightly from a median of 19 to 15 ( P = .02). Comparison of baseline with week-12 Physician Global Assessment scores, and secondary outcome measures of lesion counts and patient pain scores, failed to show statistically significant improvement. Etanercept was generally well tolerated; however, two patients discontinued the study as a result of skin infections at the site of hidradenitis lesions requiring oral antibiotics. Limitations Lack of a control group and a small number of participants are limitations. Conclusions Our study demonstrated minimal evidence of clinically significant efficacy of etanercept (50 mg/wk subcutaneously) in the treatment of hidradenitis. Future studies using higher doses of etanercept are indicated; however, patients need to be carefully monitored for infection and other adverse events. Randomized, controlled trials will be necessary to demonstrate the risk-to-benefit ratio of tumor necrosis factor-α inhibitors in the treatment of hidradenitis.

Skin is the largest human organ, accounting for approximately 12-15% of body weight.1 Volatile organic compounds (VOCs) emanating from skin contribute to a person’s body odour, and may convey important information about metabolic processes. VOCs from skin derive from eccrine, sebaceous and apocrine gland secretions and their interactions with resident skin bacteria.2,3 These glands are distributed differently across the body; hence different regions of the body have different VOC profiles, and thus different odours. Eccrine glands are found throughout the skin, but are especially concentrated in palms of hands, soles of feet, and the forehead. Eccrine sweat is mostly water, but contains glycoproteins (notably interleukin 1), lactic acid, sugars, amino acids and electrolytes.4 Sebaceous glands are concentrated on the upper part of the body.3 The upper chest, back, scalp, face and forehead may have as many as 400-900 sebaceous glands cm-2. Sebaceous gland secretions are rich in lipid materials such as cholesterol, cholesterol esters, long-chain fatty acids, squalene and triglycerides.3 These lipids provide substrate for growth and metabolism of skin microorganisms. Apocrine glands are concentrated in the axillae, pubic area and areolas.2,4 Apocrine secretions are the chief source of underarm odorants (commonly known as ‘body odour’) and play a role in chemical signalling (for a review see Wysocki and Preti.5) Many previous studies have focused on VOCs emanating from the axillae, which reflect some contribution from all skin glands located in the axillae.6-10 VOCs from nonaxillary skin secretions have been studied as potential mosquito attractants,11-13 indicators of seasonal changes14 and ageing,15 and moderators of fragrances.16-19 It was recently demonstrated that skin emanations could be collected via rolling a stir-bar coated with polydimethylsiloxane across the arm with subsequent desorption and analysis by gas chromatography/mass spectrometry (GC/MS).20 Bernier et al.11-13 reported that hundreds of compounds canbe volatilized from skin secretions collected from the palms and backs of hands. Most of these compounds have been documented to be organic acids ranging in carbon size from C2 to C20. However, the most abundant (75-80%) organic acids found on skin are C16 and C18 saturated, monounsaturated and diunsaturated acids,12 which are not volatile at body temperatures. In contrast, collection of skin VOCs using solid-phase microextraction (SPME) will collect low molecular weight compounds that are volatile at body temperature. SPME-GC/MS analyses of hand/wrist VOCs sampled in both winter and spring revealed 35 organic compounds.14 VOCs were reported to be more abundant in winter samples; however, the relative ratios of many (but not all) of the compounds did not vary between seasons. This observation led the authors to speculate that the moist spring air allowed the skin to harbour more bacteria that hydrolysed and decomposed some of the VOCs. A study of male Japanese subjects used T-shirts worn for 3 days to collect skin odours. VOCs emanating from rectangular pieces cut from the backs of these T-shirts were studied.15 The authors suggested that skin secretions in men older than age 39 years contain larger amounts of unsaturated aldehydes than secretions from younger men. These compounds, particularly 2-nonenal, were reported to impart an unpleasant ‘ageing odour’ to older Japanese men. Most acids, alcohols and aldehydes found in skin secretions apparently originate from the interactions between sebaceous gland secretions and cutaneous bacteria.12,21 Anaerobic bacteria living in the hair follicle/sebaceous gland duct use lipases to liberate long-chain acids from triglycerides, which are further metabolized by aerobic bacteria into longer, saturated and unsaturated acids and smaller volatile acids, aldehydes and alcohols.21 Other potential sources of skin volatiles are putative odorants carried by the apocrine secretion odour-binding protein (ASOB) 1.22 This protein might bind odorous acids that can be liberated by interaction with cutaneous bacteria. A previous study demonstrated that this protein does carry odorants in the underarm, and is present in sebaceous-rich perspiration from the forehead.22 Tracking dogs trained to recognize an individual’s scent on garments from a particular body part (e.g. chest, arm, leg) are not reliably able to generalize the individual’s odour to other body parts, suggesting that a different odorant milieu may characterize the back and forearm (for a review see Jenkins23). In this study, we performed a comprehensive analysis of VOCs from the upper back and forearm of 25 healthy subjects using two complementary sampling techniques, SPME and solvent extraction. Skin secretions from the back of each subject also were analysed for the presence of the potential VOC carrier ASOB1. The goals of the study were: (i) to identify VOCs emanating from the upper back and forearm skin; (ii) to determine whether VOCs vary in a qualitative or quantitative manner; and (iii) to determine if VOCs vary in relative abundance with gender, age or locus, i.e. back and forearm. The upper back and forearm were chosen because they are easily accessible with minimal inconvenience to subjects. In addition, these body regions differ with respect to density of sebaceous glands (upper back > forearm) and skin bacteria, as well as exposure to sun, environment and consumer products.3,21

Background: There are no current instruments to facilitate population screening for rosacea. Objective: To develop and evaluate a screening instrument for rosacea applicable for population surveys. Methods: A rosacea-specific screening instrument (Rosascreen), consisting of a subject-completed questionnaire and screening algorithm, was developed based on current diagnostic criteria for rosacea. Three iterations were pilot tested and refined for clarity and sensitivity in adult outpatients with and without rosacea. Results: Three subject groups were consecutively evaluated with iterations of the questionnaire at each centre (overall N = 121). The final version had a sensitivity of 93% to 100% for key diagnostic criteria, and use of the algorithm had a sensitivity of 100% for detection of rosacea and specificity of 63% to 71%. Most subjects found the questionnaire easy to understand and complete. Conclusion: Rosascreen, a subject-completed questionnaire and diagnostic algorithm, is a highly sensitive screening instrument that may facilitate estimation of rosacea prevalence in general populations.

Disclaimer Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be deemed inclusive of all proper methods of care or exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient.

Scarring is a lifelong, physically disfiguring and often emotionally debilitating sequela resulting from acne vulgaris. Nearly 80% of patients have some scarring and 50% have clinically relevant scarring. Although the extent, duration, and intensity of inflammation are important risk factors, scarring also can develop in patients with relatively mild inflammation. Assessment of scarring should be part of the evaluation in all patients with acne and should be a consideration in determining treatment. Semin Cutan Med Surg 34(supp5):S89-S91 © 2015 published by Frontline Medical Communications.

The development of a hydrogel to stabilize and solubilize clindamycin and tretinoin provides a single, once-daily treatment for acne vulgaris.Our aim was to compare the efficacy and safety of the combination of clindamycin (1%) and tretinoin (0.025%) with each agent alone and vehicle.Two randomized, double-blind, active drug- and vehicle-controlled 12-week studies evaluated inflammatory and noninflammatory lesion counts and the Investigator's Static Global Assessment in 2219 subjects with acne vulgaris.The combination demonstrated superior efficacy to clindamycin, tretinoin, and vehicle. Combination hydrogel was significantly more effective in reducing inflammatory (P.005), noninflammatory (Por = .0004), and total (P.0001) lesion counts than the other treatments and vehicle. The proportion of subjects with clear or almost clear skin on the Investigator's Static Global Assessment was greater with the combination (P.0001).A majority of subjects (82.6%) had grade 2-3 acne vulgaris at baseline; therefore these overall results may not be representative of the response in the subjects (17.4%) with grade 4-5 acne.The combination clindamycin/tretinoin hydrogel was well tolerated and significantly more effective than clindamycin, tretinoin, or vehicle for the treatment of acne vulgaris.

Objective: The goal of this review was to summarize the available literature covering the safety profiles of oral doxycycline and minocycline. Methods: Scientific literature published between 1966 and August 2003 was searched using the MEDLINE, EMBASE, and Biosis databases (search terms: minocycline or doxycycline , each paired with adverse reaction, adverse event , and side effect , and doxycycline or minocycline with the limits English language, human , and clinical trials ). Safety information was collected from case reports and clinical trials. Adverse event (AE) rates in the United States were calculated by comparing data from the MedWatch AE reporting program used by the US Food and Drug Administration (FDA) with the number of new prescriptions dispensed for each drug from January 1998 to August 2003. Results: Between 1966 and 2003, a total of 130 and 333 AEs were published in case reports of doxycycline and minocycline, respectively. In 24 doxycycline clinical trials (n = 3833) and 11 minocycline trials (n = 788), the ranges in incidence of AEs were 0% to 61% and 11.7% to 83.3%, respectively. Gastrointestinal AEs were most common with doxycycline; central nervous system and gastrointestinal AEs were most common with minocycline. From January 1998 to August 2003, the FDA MedWatch data contained 628 events for doxycycline and 1099 events for minocycline reported in the United States. Approximately 47,630,000 doxycycline and 15,234,000 minocycline new prescriptions were dispensed in the United States during that period, yielding event rates of 13 per million for doxycycline and 72 per million for minocycline, based on FDA data. Conclusions: Between 1998 and 2003, doxycycline was prescribed 3 times as often as minocycline. The incidence of AEs with either drug is very low, but doxycycline had fewer reported AEs. Although more head-to-head clinical trials are needed for a direct comparison of AE frequency, these preliminary data from separate reports suggest the possibility that AEs may be less likely with doxycycline than minocycline.

Learning Objectives After completing this course, the reader will be able to: Describe the clinical and pathological characteristics of the cutaneous rash secondary to anti-EGFR therapy.Explain the prognostic implications of the cutaneous rash secondary to anti-EGFR therapy.Discuss the treatment of the cutaneous rash secondary to anti-EGFR therapy. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com Skin rash associated with HER1/epidermal growth factor receptor (EGFR) inhibitors is common. The lack of clinical and patient guidance for this often chronic and sometimes distressing side effect makes rash management and etiology investigation high priorities. To address this, oncologists and dermatologists with experience with HER1/EGFR inhibitors attended the HER1/EGFR Inhibitor Rash Management Forum. Recommendations include continued analysis of the correlation between rash and clinical outcome and improving the accuracy and reproducibility of terminology and grading systems. Because acne vulgaris has a unique pathology, and the pathology and etiology of rash are unclear yet distinct from acne vulgaris, using such terms as acne, acne-like, or acneiform should be avoided. Until there is a specific dermatological definition, rash is best described using phenotypic terms for its appearance and location. It is currently unknown which agents are best for treating rash. Clinical trials of rash treatments are urgently required, and suggestions for agents to consider are made based on current knowledge. The effect of dose reduction or interruption on rash should also be investigated. Secondarily infected rash may be more frequent than has been previously recognized, and some investigators favor empiric use of an oral antibiotic if this appears to be the case. Suggestions for patients include makeup to camouflage the rash and an emollient to prevent and alleviate skin dryness. The increasing use of HER1/EGFR-targeted agents makes managing rash important. We hope the outcomes from this Forum provide background for future studies.

Background: Despite published data showing the efficacy of topical retinoids in treating inflammatory acne, in clinical practice topical retinoids tend to be used most commonly for noninflammatory acne. Objective: The goal of this study was to assess theefficacy of topical retinoids as monotherapy in inflammatory acne. Methods: This retrospective, investigator-blinded,vehicle-controlled, photographic assessment study was conducted by 5 investigators. The investigators rated pretreatment and posttreatment photographs of patients who had participated in 12- or 15-week, double-blind comparisons of tazarotene 0.1% gel, adapalene 0.1% gel, tretinoin 0.1% microsponge, tretinoin 0.025% gel, and tazarotene 0.1% cream (vehicle). Acne severity was rated on a 7-point scale. A posttreatment increase or decrease of 1 grade was considered clinically meaningful; ≥2 grades was considered an even clearer measure of clinically significant improvement. Investigators also rated global response to treatment on a 7-point scale. A posttreatment increase of ≥2 grades was considered a clinically relevant improvement. Results: Each of the 5 investigators rated photographs of 577 patients (∼52% women, ∼48% men; mean age, 18–20 years), for a total of 2885 evaluations (in addition to daily evaluations of the 20 control patients). The treatment groups consisted of tazarotene (252 patients, 1260 evaluations), adapalene (178 patients, 890 evaluations), tretinoin microsponge (47 patients, 235 evaluations), tretinoin gel (39 patients, 195 evaluations), and vehicle (61 patients, 305 evaluations). Inflammatory acne was improved with all 4 retinoids compared with vehicle. In 1905 evaluations in which pretreatment acne severity was grade ≥3 (mild to moderate), the incidences of clinically significant improvements in the tazarotene, adapalene, and tretinoin microsponge groups were 24%, 17%, and 21%, respectively (all, P ≤ 0.001 vs vehicle [7%]). The difference in prevalence of clinically significant improvement was statistically similar between the tretinoin gel and vehicle groups. The incidences of clinically relevant improvement in global response to tazarotene, adapalene, tretinoin microsponge, and tretinoin gel were 36%, 34%, 31%, and 28%, respectively ( P ≤ 0.001, ≤0.001, ≤0.001, and ≤0.01, respectively, vs vehicle [17%]). Conclusions: The results of this study suggest thattopical retinoid monotherapy can achieve clinically significant improvements in inflammatory acne.

Topical retinoids are one of the most effective classes of topical drugs used to treat acne vulgaris. The effects of the gel formulation of the topical retinoid tazarotene have been widely reported, but few data on the cream formulation are available.The primary aim of the 2 studies reported in this article was to determine the effects of tazarotene 0.1 % cream in patients with facial acne vulgaris.Two randomized, double-blind, parallel-group studies were performed. The first was conducted at 14 investigational sites across the United States, and the second took place at 15 sites, with 5 of these providing blood samples for analysis of tazarotenic acid. In both studies, patients agedor =12 years with facial acne vulgaris were randomized to receive tazarotene or vehicle cream QD for 12 weeks. Lesion counts (noninflammatory, inflammatory, and total) and overall clinical and global assessments were made at weeks 0 (baseline), 4, 8, and 12. Adverse events (AEs) were monitored throughout the study In one of the studies, therapeutic drug monitoring was performed at weeks 4 and 8 in members of the study population who gave consent for blood withdrawal.Eight hundred forty-seven patients were enrolled in the 2 studies (430 males, 417 females; mean age,19 years; age range, 11-52 years [1 patient was entered into the study at age 11 years, in violation of the protocol]). At 12 weeks, the median percentage changes from baseline in all 3 lesion counts were significantly lower with tazarotene than with vehicle (all, P0.001), as were the overall clinical and global responses (both, P0.001). Treatment-related AEs whose incidence was higher with tazarotene than with vehicle included desquamation, dry skin, erythema, a burning sensation on the skin, and skin irritation (all, P0.001) and pruritus (P0.01); most (83%-98%) were mild or moderate. Systemic exposure to tazarotenic acid was limited (mean,0.1 ng/mL) and did not increase with time.In these 2 studies in adolescent and adult patients with facial acne vulgaris, tazarotene 0.1%cream QD for 12 weeks was effective and well tolerated. Systemic exposure to tazarotenic acid was limited.

INTRODUCTION In the past 25 years, numerous topical and systemic drugs have been developed for the treatment of acne vulgaris. The voluminous amount of clinical trial information has become increasingly difficult for individual physicians to monitor. Clinical trials are a science no different than any other aspect of medicine. There has been improvement in the design and performance of clinical trials in the past several years. Currently, most authoritative opinions fully support the need for studies to be performed under the CONSORT and Cochrane principles. We accept that many studies have not been as rigorously performed in the past as trials done in 2002. But to discard such studies is inappropriate, because they were done well according to the standards of the time. Thus, for the time being, clinical opinion, based in part on formal discussion among expert colleagues with an interest in acne and a logical analysis of the literature, is not unreasonable as the basis for a Consensus Recommendation. Such recommendations highlight the indications for use of medications and the optimal approach to the management of specific clinical problems. Overall, the goal is to provide a comprehensive overview of rational therapy, which can form the basis for more uniform therapeutic strategies throughout the world, enhanced patient compliance, and more effective use of healthcare resources. Several sets of guidelines have been developed for the treatment of acne during the past decade, including a practice guideline for the Oral Treatment of Acne in France (1999), Canadian Acne Treatment Guidelines (1995), German Guidelines for Acne Treatment (2001), Treatment of Acne Vulgaris: Guidelines for Primary Care Physicians (1991), and Guidelines of Care for Acne Vulgaris from the American Academy of Dermatology (1990). However, advances in medicine occur relatively rapidly, and practice guidelines may be out of date shortly after they are issued. Thus, there is a continuing need to update existing recommendations so that recent advances in therapy can be brought to the attention of physicians in a timely manner. In recognition of this need, this supplement to the Journal of the American Academy of Dermatology has been developed by a panel of physicians and researchers in the field of acne, working together as a Global Alliance to Improve Outcomes in Acne. The mission of this group is to develop consensus recommendations for the treatment of acne, which are evidence-based when possible, and which include input from numerous countries. The members of the group represent a broad list of international dermatologists with a special interest in acne and reflect a wide range of experiences and opinions. The activities of the group have been coordinated by Dimensional Healthcare, Inc, and funded by an educational grant from Galderma. As might be expected, some of the physicians involved in the development of this document have past or current, direct or indirect financial

Background Bovine collagen is extensively used for facial soft tissue augmentation but provides only temporary correction and can cause hypersensitivity reactions. Hyaluronic acid derivatives potentially offer improved longevity of correction and a reduced risk of immunogenicity and hypersensitivity. Objective To compare the efficacy and safety of nonanimal stabilized hyaluronic acid gel (Restylane; Q-Med, Uppsala, Sweden) with that of bovine collagen (Zyplast) for treatment of nasolabial folds. Methods One hundred thirty-eight patients with prominent nasolabial folds were randomized to treatment with hyaluronic acid gel and bovine collagen on contralateral sides of the face. Treatments were repeated at 2-week intervals, as required, to achieve "optimal cosmetic result" (baseline). Outcomes were evaluated by a blinded investigator at 2, 4, and 6 months after baseline. Results Less injection volume was required for "optimal cosmetic result" with hyaluronic acid gel than with bovine collagen, and patients and investigators judged hyaluronic acid gel to be more effective in maintaining cosmetic correction. The investigator-based Wrinkle Severity Rating Scale and Global Aesthetic Improvement Scale assessments at 6 months after baseline indicated that hyaluronic acid gel was superior in 56.9% and 62.0% of patients, respectively, whereas bovine collagen was superior in 9.5% and 8.0% of patients, respectively. The frequency, intensity, and duration of local injection-site reactions were similar for the two products. Conclusion Nonanimal stabilized hyaluronic acid provides a more durable aesthetic improvement than bovine collagen and is well tolerated.

Human underarm secretions, when applied to women recipients, alter the length and timing of the menstrual cycle. These effects are thought to arise from exposure to primer pheromones that are produced in the underarm. Pheromones can affect endocrine (primer) or behavioral (releaser) responses, provide information (signaler), or perhaps even modify emotion or mood (modulator). In this study, we extracted underarm secretions from pads worn by men and placed the extract under the nose of women volunteers while monitoring serum LH and emotion/mood. Pulses of LH are excellent indicators of the release of GnRH from the brain's hypothalamus. In women, the positive influence of GnRH on LH affects the length and timing of the menstrual cycle, which, in turn, affects fertility. Here we show that extracts of male axillary secretions have a direct effect upon LH-pulsing and mood of women. In our subjects, the putative male pheromone(s) advanced the onset of the next peak of LH after its application, reduced tension, and increased relaxation. These results demonstrate that male axillary secretions contain one or more constituents that act as primer and modulator pheromones.

Background. Recent reports indicate that laser hair removal is most effective on anagen hairs. However, no published trials have examined laser epilation after hair cycle synchronization. Objective. To evaluate the potential for enhanced laser hair removal after the induction of telogen hairs into anagen by wax epilation. Methods. We identified four 2.5-cm square areas with equivalent hair length and density on the backs of 13 dark-haired white men. To induce typically telogen hairs into anagen, two areas on each patient were wax epilated. Two weeks later, one waxed area and one unwaxed area were treated with a long-pulsed alexandrite laser. One month after laser treatment, a subjective comparison was made based on hair density, length, and thickness. Results. In 12 of 13 patients, lasered areas that had been pretreated with wax epilation were clearer of hair as compared with areas that had been pretreated by shaving (P=0.0034). No significant difference was noted between waxed and unwaxed control areas that had not been laser treated (P=1.0). Conclusion. Wax epilation 2 weeks before laser hair removal improves cosmetic outcomes at 1 month. This effect may be secondary to the recruitment and heightened sensitivity of early anagen hairs.

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.

Background/aims: This study investigated the effect of specific, commonly used diaper types on scrotal temperatures in normal healthy, young boys. These included both modern disposable and reusable diapers as well as various types of protective outer coverings that are in common use in both North America and Europe Methods: Scrotal and skin surface temperatures were continuously monitored in healthy, young males using a computerized data-logging system based on temperature probes specifically designed for paediatric studies. These systems could be used either tethered to the PC or made completely portable depending upon the age and activity of the child being measured. Based on our results from several pilot studies, it became clear that the best way to determine if disposable and reusable diapers differ with regard to their impact on scrotal temperatures is to run these comparisons under controlled laboratory conditions where ‘diaper type’ was the primary variable. A 2-h time period was chosen to ensure that sufficient time had elapsed for thermal equilibrium to be established under the diapers. We also felt it necessary to study the impact of urination and simulated this condition over the last 15 min using standardized methods. In addition to the skin surface temperatures, we also measured the temperature of the tympanic membrane using an infrared thermometer as an estimate of ‘core’ temperature for each individual at various times during the session. Results and Conclusions: In this study, we have clearly shown that scrotal temperatures are the same whether the child is wearing disposable or reusable cloth diapers with a protective cover. The only situation in which scrotal temperatures were found to be lower is when the cloth diaper is used alone without a protective cover but this is not representative of how these products are actually used. We also found that on average scrotal temperatures are significantly lower than core for each diaper type. Occasionally, we did see individuals in which the maximal scrotal temperatures approached core temperatures but in every case the thermal sensors were soiled by a bowel movement. We also found that skin surface temperatures increased not only when covered by a diaper but also due to the thermal insulation provided by outer garments and blankets.

Two-hundred-and-eight acne vulgaris patients were enrolled in a 24-week study to determine the bacterial resistance issues associated with the use of a topical 2% erythromycin gel. It consisted of a 12-week randomized, double-blind, parallel-group treatment phase comparing the active gel versus its vehicle followed by a 12-week single-blind regression phase with gel vehicle only. Bacteriological samples were taken from the face, back and nares for quantification by species and antibiotic resistance characteristics. Acne efficacy was assessed through week 12. The prevalence of erythromycin-resistant coagulase-negative Staphylococci on the face was extremely high (87%) at baseline, increased to 98% by week 12 in the erythromycin-treated group and did not change during regression. The density of these resistant organisms also significantly increased with erythromycin treatment with no change during regression. Similar prevalence and density patterns were also observed on the untreated back and in the nares. Nearly all of the resistant isolates were highly resistant (minimal inhibitory concentrations > 128 microg/ml). Resistance development was confined to the macrolide class of antibiotics. No anti-acne efficacy was observed.

Importance The notion that systemic isotretinoin taken within 6 to 12 months of cutaneous surgery contributes to abnormal scarring or delayed wound healing is widely taught and practiced; however, it is based on 3 small case series from the mid-1980s. Objective To evaluate the body of literature to provide evidence-based recommendations regarding the safety of procedural interventions performed either concurrently with, or immediately following the cessation of systemic isotretinoin therapy. Evidence Review A panel of national experts in pediatric dermatology, procedural/cosmetic dermatology, plastic surgery, scars, wound healing, acne, and isotretinoin was convened. A systematic PubMed review of English-language articles published from 1982 to 2017 was performed using the following search terms: isotretinoin, 13-cis-retinoic acid, Accutane, retinoids, acitretin, surgery, surgical, laser, ablative laser, nonablative laser, laser hair removal, chemical peel, dermabrasion, wound healing, safety, scarring, hypertrophic scar, and keloid. Evidence was graded, and expert consensus was obtained. Findings Thirty-two relevant publications reported 1485 procedures. There was insufficient evidence to support delaying manual dermabrasion, superficial chemical peels, cutaneous surgery, laser hair removal, and fractional ablative and nonablative laser procedures for patients currently receiving or having recently completed isotretinoin therapy. Based on the available literature, mechanical dermabrasion and fully ablative laser are not recommended in the setting of systemic isotretinoin treatment. Conclusions and Relevance Physicians and patients may have an evidence-based discussion regarding the known risk of cutaneous surgical procedures in the setting of systemic isotretinoin therapy. For some patients and some conditions, an informed decision may lead to earlier and potentially more effective interventions.

Isotretinoin-Lidose, the first new formulation of isotretinoin in 30 years, differs from previously approved isotretinoin formulations in that it is less dependent on the presence of fat in the gut for absorption.Evaluate the safety profiles of isotretinoin-Lidose and food-dependent generic isotretinoin in the largest clinical study with isotretinoin-925 randomized patients from 49 study sites. Determine if the efficacy of this new formulation is noninferior to an existing isotretinoin.Multicenter, double-blind, randomized, parallel-group, noninferiority trial. Study medication was taken with meals twice daily for 20 weeks. Patients were followed for 4 weeks after the last dose. Safety evaluations included recordings of adverse events, assessments for depression, anxiety, emergent psychotic symptoms, and suicidal ideation/behavior, as well as DEXA and X-ray evaluations and changes in bone age. Two co-primary efficacy outcomes were measured to assess noninferiority: a) change in total nodular facial and truncal lesion count at from baseline to week 20 and b) percentage of patients who experienced at least 90% reduction in nodular facial and truncal lesion count from baseline to week 20.Although isotretinoin-Lidose can be taken without meals, it was given with food because the absorption of both formulations in the study had to be similar to detect noninferiority.The safety profile of the 2 formulations was comparable. Criteria for noninferiority for both co-primary efficacy outcomes were met based on predetermined margins.Safety and efficacy of isotretinoin-Lidose is similar and noninferior to food-dependent generic isotretinoin, respectively.

Compare the safety and efficacy of 1% and 5% silica encapsulated benzoyl peroxide (E-BPO) in patients with papulopustular rosacea.Multi-centered randomized, double blind, vehicle controlled parallel group, 12 week treatment in 92 patients with papulopustular rosacea. Primary endpoints were dichotomized IGA with success defined as clear/near clear and reduction in inflammatory lesions.92 patients: 74% graded as moderate IGA, 14% severe and 12% mild. The mean inflammatory lesion count was 24.Once daily treatment for 12 weeks with vehicle, 1% or 5% E-BPO.1% and 5% E-BPO were superior to vehicle in reducing papulopustular lesions P =0.01 and P =0.02. 5% E-BPO was superior to vehicle for IGA P =0.0013.

Background/Objectives: Widespread use of antibiotics in all areas of medicine has led to significant problems with antimicrobial resistance, which have begun to compromise the usefulness of antibiotics. Antibiotics have long been a keystone of acne therapy. There is a large population of patients with acne and antibiotic therapy is often used for long durations; thus, acne therapy results in extensive antibiotic exposure. This article discusses the role of antibiotic therapy in acne from the perspective of how clinicians can best preserve the utility of these important drugs while providing efficacious and safe therapy for acne patients. Methods: Review of literature augmented by expert opinion when literature was sparse. Results: Antibiotic monotherapy (topical or oral) is not recommended due to the availability of clinically superior regimens. Systemic antibiotics are important for managing moderate to severe acne and should be used for a limited duration of time (3-4 months). Topical antibiotics should be paired with benzoyl peroxide to limit potential for resistance. Information gained in recent years about the pathophysiology of acne has shed light on the role of Propionibacterium acnes as well as other key pathogenic pathways such as inflammation. Conclusions: The improved understanding of acne pathogenic mechanisms can and should be applied to develop modern therapeutic approaches that are efficacious and mesh with current public health concerns.

This review summarizes current information regarding the use of antimicrobial agents for the treatment of patients with inflammatory acne. A number of drugs have been used effectively as topical or systemic therapy, often in combination with benzoyl peroxide or a retinoid. Propionibacterium acnes exhibits high in vitro sensitivity to a wide range of antimicrobials, including ampicillin, clindamycin, erythromycin, tetracycline, doxycycline, nadifloxacin, ofloxacin, minocycline, cephalexin, and gentamycin. However, not all of these drugs are equally effective in penetrating the lipid-filled microcomedo and reducing numbers of P. acnes in the skin. Antimicrobial therapy, particularly systemic treatment, may be complicated by the potential for drug-drug interactions. Historically, the potential for antimicrobials to reduce the effectiveness of oral contraceptives has been a concern in the treatment of acne. However, there is evidence to suggest that such an interaction does not take place in patients being treated with the antimicrobials most often used in dermatological practice. Antimicrobial therapy for acne has also been complicated by the emergence of antibiotic-resistant strains of P. acnes. Increasing P. acnes resistance can be combated by judicious use of retinoids in combination with antibiotics to reduce inflammation and infection, and employment of retinoids for maintenance therapy.

Propionibacterium acnes is a member of the resident cutaneous flora. Sebaceous follicles involved in acne are characterized by the accumulation of abnormally desquamated corneocytes and excess sebum-the microcomedo. This environment provides ideal growth conditions for P acnes. Several orders of magnitude level of P acnes are found in microcomedos. P acnes produces a variety of chemotactic factors and proinflammatory molecules that are responsible for the inflammatory phase of acne. Antibiotic therapy works by reducing the viable number of P acnes as well as by reducing the production of inflammatory stimuli. Antibiotic therapy has been a mainstay of treatment for more than 30 years. In the last decade, decreased sensitivity to antibiotics has developed and clinical resistance has been described. This development threatens the usefulness of antibiotic therapy in the future.

The detergent sodium dodecyl sulfate is a well-known inducer of irritant contact dermatitis. In this study we show that sodium dodecyl sulfate induces the serine proteinase inhibitor, plasminogen activator inhibitor type 2, in epidermal keratinocytes. The enhancement in plasminogen activator inhibitor type 2 mRNA and antigen is observed both when sodium dodecyl sulfate is applied topically to normal human skin as well as when it is added to the growth medium of cultured human keratinocytes. In vitro , plasminogen activator inhibitor type 2 mRNA is increased within 4–8 h after addition of the detergent, and the increase in plasminogen activator inhibitor type 2 antigen occurs slightly later. The enhancing effect of sodium dodecyl sulfate on plasminogen activator inhibitor type 2 is not related to nonspecific cell lysis nor is it secondary to induction of tumor necrosis factor α. Similarities between our in vitro and in vivo findings lead us to hypothesize that sodium dodecyl sulfate may exert its effect on epidermal plasminogen activator inhibitor type 2 via interaction with the keratinocyte.