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Importance: Although isotretinoin may rarely be associated with laboratory abnormalities such as hypertriglyceridemia, the optimal approach to laboratory monitoring is uncertain, and there is wide variation in clinical practice., Objective: To establish a consensus for isotretinoin laboratory monitoring among a diverse, international cohort of clinical and research experts in acne., Design, Setting, and Participants: Using a modified electronic Delphi process, 4 rounds of anonymous electronic surveys were administered from 2021 to 2022. For laboratory tests reaching consensus (≥70% agreement) for inclusion, questions regarding more time-specific monitoring throughout isotretinoin therapy were asked in subsequent rounds. The participants were international board-certified dermatologist acne experts who were selected on a voluntary basis based on involvement in acne-related professional organizations and research., Main Outcomes and Measures: The primary outcome measured was whether participants could reach consensus on key isotretinoin laboratory monitoring parameters., Results: The 22 participants from 5 continents had a mean (SD) time in practice of 23.7 (11.6) years and represented a variety of practice settings. Throughout the 4-round study, participation rates ranged from 90% to 100%. Consensus was achieved for the following: check alanine aminotransferase within a month prior to initiation (89.5%) and at peak dose (89.5%) but not monthly (76.2%) or after treatment completion (73.7%); check triglycerides within a month prior to initiation (89.5%) and at peak dose (78.9%) but not monthly (84.2%) or after treatment completion (73.7%); do not check complete blood cell count or basic metabolic panel parameters at any point during isotretinoin treatment (all >70%); do not check gamma-glutamyl transferase (78.9%), bilirubin (81.0%), albumin (72.7%), total protein (72.7%), low-density lipoprotein (73.7%), high-density lipoprotein (73.7%), or C-reactive protein (77.3%)., Conclusions and Relevance: This Delphi study identified a core set of laboratory tests that should be evaluated prior to and during treatment with isotretinoin. These results provide valuable data to guide clinical practice and clinical guideline development to optimize laboratory monitoring in patients treated with isotretinoin.

Background: Acne vulgaris often affects the face, shoulders, chest, and back, but treatment of nonfacial acne has not been rigorously studied., Objectives: Assess the safety and efficacy of trifarotene 50 μg/g cream, a novel topical retinoid, in moderate facial and truncal acne., Methods: Two phase III double-blind, randomized, vehicle-controlled, 12-week studies of once-daily trifarotene cream versus vehicle in subjects aged 9 years or older. The primary end points were rate of success on the face, as determined by the Investigator's Global Assessment (clear or almost clear and ≥2-grade improvement), and absolute change from baseline in inflammatory and noninflammatory counts from baseline to week 12. The secondary end points were rate of success on the trunk (clear or almost clear and ≥2-grade improvement) and absolute change in truncal inflammatory and noninflammatory counts from baseline to week 12. Safety was assessed through adverse events, local tolerability, vital signs, and routine laboratory testing results., Results: In both studies, at week 12 the facial success rates according to the Investigator's Global Assessment and truncal Physician's Global Assessment and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P < .001) in favor of trifarotene when compared with the vehicle., Limitations: Adjunctive topical or systemic treatments were not studied., Conclusion: These studies demonstrate that trifarotene appears to be safe, effective, and well tolerated in treatment of both facial and truncal acne., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Rosacea is currently treated according to subtypes. As this does not adequately address the spectrum of clinical presentation (phenotypes), it has implications for patient management. The ROSacea COnsensus panel was established to address this issue., Objectives: To incorporate current best treatment evidence with clinical experience from an international expert panel and establish consensus to improve outcomes for patients with rosacea., Methods: Seventeen dermatologists and three ophthalmologists reached consensus on critical aspects of rosacea treatment and management using a modified Delphi approach. The panel voted on statements using the responses 'strongly disagree', 'disagree', 'agree' or 'strongly agree'. Consensus was defined as ≥ 75% 'agree' or 'strongly agree'. All voting was electronic and blinded., Results: The panel agreed on phenotype-based treatments for signs and symptoms presenting in individuals with rosacea. First-line treatments were identified for individual major features of transient and persistent erythema, inflammatory papules/pustules, telangiectasia and phyma, underpinned by general skincare measures. Multiple features in an individual patient can be simultaneously treated with multiple agents. If treatment is inadequate given appropriate duration, another first-line option or the addition of another first-line agent should be considered. Maintenance treatment depends on treatment modality and patient preferences. Ophthalmological referral for all but the mildest ocular features should be considered. Lid hygiene and artificial tears in addition to medications are used to treat ocular rosacea., Conclusions: Rosacea diagnosis and treatment should be based on clinical presentation. Consensus was achieved to support this approach for rosacea treatment strategies., (© 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

In part 1 of this 3-part series, an overview of the epidemiology, visible patterns, and important considerations for clinical and laboratory evaluation of acne vulgaris (AV) in adult women was provided. Proper selection and integration of skin care products is important in the management of AV in this patient population. Part 2 of this series includes a discussion of over-the-counter and prescription topical therapies for adult women with AV. A summary of key randomized controlled trials also is provided. Further well-designed studies are needed, as data on the use of topical agents in this subpopulation are limited.

The last article in this 5-part series provides a final overview of consensus recommendations from the American Acne & Rosacea Society (AARS) on the management of the common presentations of cutaneous rosacea. Optimal management of rosacea requires careful assessment of the patient's clinical features with integration of therapies that adequately treat the presenting signs and symptoms. The treatment consensus recommendations from the AARS are based on 2 major common clinical presentations of rosacea: (1) centrofacial erythema with papulopustular lesions, and (2) centrofacial erythema without papulopustular lesions. The recommendations provided here serve to guide clinicians in their clinical practice.

The third article in this 5-part series reviews systemic therapies used to treat cutaneous rosacea based on consensus recommendations from the American Acne & Rosacea Society (AARS) on the management of the common presentations of cutaneous rosacea. The consensus recommendations are based on current understanding of research that describes pathophysiologic mechanisms that appear to be operative in rosacea, correlation of these underlying pathophysiologic mechanisms with specific clinical manifestations of rosacea, and outcomes from clinical trials that evaluate therapies for rosacea both as monotherapy and in combination with other agents. Systemic agents used for treatment of rosacea have been administered as oral formulations (ie, tablets, capsules). The only oral agent for rosacea approved by the US Food and Drug Administration (FDA) is a modified-release doxycycline 40-mg capsule. Other non-FDA-approved oral agents also are discussed including other tetracyclines, macrolides, metronidazole, and isotretinoin.

A variety of topical therapies have been utilized in the treatment of rosacea. In part 2 of this 5-part series, topical agents that have been utilized in the treatment of the common clinical presentations of rosacea, including those that have been approved by the US Food and Drug Administration (FDA) as well as alternative agents, are reviewed. It is important to note that adjunctive skin care and photoprotection are integral components of rosacea treatment that may assist in optimizing therapeutic outcomes.

Background: Moderate to severe acne vulgaris is often treated with a combination of an oral antibiotic, topical antibiotic/retinoid, and benzoyl peroxide (BP), but data are limited on the efficacy of this and other combination regimens that incorporate both oral and topical therapies.
, Methods: Patients were required to be aged 12-30 years with moderate to severe acne (grades 3-4 acne on the Investigator's Global Assessment [IGA]) and deemed potential candidates for treatment with isotretinoin. Enrolled patients were given triple-combination therapy, defined in this study as oral minocycline HCl extended release 1 mg/kg QD, 6% BP foaming cloths used QD, and clindamycin phosphate 1.2%/tretinoin 0.025% gel applied QD, and were evaluated at baseline and weeks 2, 4, 8, and 12.
, Results: A total of 97 patients were enrolled in the study. At week 12, 89% of patients had at least a one-grade improvement from baseline IGA and 96% had at least a one-grade improvement from baseline Global Aesthetic Improvement Scale score. Mean ± SD in- flammatory, non-inflammatory, and total lesion counts decreased from baseline by 61.8% ± 38.3%, 48.8% ± 34.5%, and 56.5% ± 29.9%, respectively. The percentage of patients evaluated as candidates for isotretinoin by independent photographic review was 77% (69/90) at baseline and only 16% (14/90) at week 12. Treatment-related adverse events (AEs) occurred in eight of 97 (8%) patients. Triplecombination therapy was not associated with any serious AEs or AEs leading to discontinuation.
, Conclusion: Triple-combination therapy was well tolerated and substantially reduced facial acne lesion counts, with 84% of patients judged to no longer be candidates for isotretinoin therapy by study end. These data support the clinical observation that a triple-combination regimen incorporating oral minocycline (dosed by patient weight), BP foaming cloths 6% QD, and clindamycin phosphate 1.2%/ tretinoin 0.025% gel QD can substantially improve moderate to severe acne vulgaris.

Acne treatment regimens have changed due to the recent over-the-counter (OTC) switch of all prescription benzoyl peroxide (BPO) topical preparations. The elimination of prescription single-agent BPO products means that dermatologists must select from a variety of OTC formulations to utilize the time-tested efficacy of BPO in the treatment of mild to moderate acne. Our research compared the efficacy and safety of an OTC BPO 5.5% formulation with lipohydroxy acid and tretinoin cream 0.025% with prescription clindamycin 1%-BPO 5% gel and tretinoin cream 0.025%. Parity was demonstrated between the 2 treatment regimens at 12 weeks.

Background: The full mechanism of action of isotretinoin [13-cis retinoic acid (13-cis RA)] in treating acne is unknown. 13-cis RA induces key genes in sebocytes that are involved in apoptosis, including Tumor necrosis factor Related Apoptosis Inducing Ligand (TRAIL)., Objectives: In this study, we investigated the role of 13-cis RA-induced TRAIL within SEB-1 sebocytes., Methods: Using 13-cis RA and recombinant human TRAIL (rhTRAIL) protein, we assessed induction of TRAIL and apoptosis in SEB-1 sebocytes, normal keratinocytes and patient skin biopsies., Results: Treatment with rhTRAIL protein increased TUNEL-positive staining in SEB-1 sebocytes. TRAIL siRNA significantly decreased the percentage of TUNEL-positive SEB-1 sebocytes in response to 13-cis RA treatment. Furthermore, TRAIL expression increased in the skin of patients with acne after 1 week of isotretinoin therapy compared with baseline. TRAIL expression localized within sebaceous glands. Unlike sebocytes, TRAIL protein expression was not increased in normal human epidermal keratinocytes in response to 13-cis RA, nor did rhTRAIL induce apoptosis in keratinocytes, suggesting that TRAIL is key in the sebocyte-specific apoptotic effects of 13-cis RA., Conclusions: Taken together, our data suggest that TRAIL, like the neutrophil gelatinase-associated lipocalin, is involved in mediating 13-cis RA apoptosis of sebocytes., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Background: A clear-cut need exists for safe and effective alternatives to the use of isotretinoin in severe acne. Lack of data regarding the specifics of isotretinoin's mechanism of action has hampered progress in this area. Recently, the protein neutrophil gelatinase-associated lipocalin (NGAL) has been identified as a mediator of the apoptotic effect of isotretinoin on sebocytes., Objectives: To establish further the clinical relevance of NGAL and to elucidate the factors that induce NGAL expression in sebocytes., Methods: Methods were developed to isolate and quantify skin-surface levels of NGAL from normal subjects and patients with acne undergoing treatment with isotretinoin., Results: Patients with acne were found to have higher skin levels of NGAL compared with normal subjects. Studies in SEB-1 sebocytes indicate that NGAL expression is increased in response to Propionibacterium acnes and interleukin (IL)-1β. In patients, isotretinoin increases NGAL levels by 2·4-fold on the skin surface and this increase precedes decreases in sebum and P. acnes counts., Conclusions: These data support the hypothesis that NGAL is an important mediator of the early effects of isotretinoin on the sebaceous glands and provide insights into the mechanisms that regulate NGAL expression in the skin., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.)

Managing acne continues to be a challenge. The data presented here provide a rationale for rethinking our approach to the use of oral antibiotics in moderate-to-severe acne and suggest strategies that favor combination regimens that limit the use of oral antibiotics.

Introduction: A solubilized 5% BPO gel has been developed to enhance the bioavailability, follicular penetration, and efficacy of BPO., Methods: Sixty-five patients with moderate facial acne vulgaris were randomly assigned to apply solubilized 5% BPO gel to one facial side and 5% BPO/1% clindamycin to the contralateral side, twice daily for four or 12 weeks., Results: The solubilized BPO gel resulted in significantly greater reductions in non-inflammatory lesion count than BPO/clindamycin at weeks 1, 2, 3, 4 and 12 and comparable reductions in inflammatory lesion count at all time points. Mean values for patient satisfaction with acne improvement were comparable and mean levels of erythema, dryness, peeling, stinging/burning and itching were consistently less than mild., Conclusion: Compared with BPO/clindamycin, the solubilized BPO gel offers significantly greater reductions in non-inflammatory lesion count and comparable reductions in inflammatory lesion count in the absence of an antibiotic.

A 3-step acne system has been developed to enhance the bioavailability and follicular penetration of benzoyl peroxide (BPO). Participants with mild to moderate facial acne vulgaris were randomly assigned to 10 weeks' facial treatment with the 3-step acne system (proprietary salicylic acid cleanser 2% twice daily, proprietary salicylic acid toner 2% once daily, and solubilized BPO gel 5% twice daily) or with control cleanser twice daily plus clindamycin 1%-BPO 5% gel (jar formulation) twice daily. Among 139 participants enrolled, the 3-step acne system was at least as effective as clindamycin-BPO in reducing noninflammatory lesion counts in the early weeks of treatment in the absence of an antibiotic (mean reductions were 27% vs 13%, 39% vs 25%, 40% vs 33%, and 42% vs 42% at weeks 2, 4, 6, and 10, respectively) (all not significant). Both regimens were associated with comparable reductions in inflammatory lesion counts at all time points. Both regimens also were generally well-tolerated with mean scores for erythema, dryness, peeling, burning/stinging, and itching less than mild in both groups at all time points. The 3-step acne system is at least as effective as clindamycin-BPO in reducing noninflammatory lesion counts in the early weeks of treatment in the absence of an antibiotic, which is likely attributed to the solubilized BPO formulation.

Treatment of acne vulgaris can be challenging for both patients and physicians. Topical retinoids are often considered first-line therapy for the treatment of all but the most severe forms of acne. A variety of formulations of topical retinoids, including adapalene and tazarotene, are available but tazarotene 0.1% gel is widely perceived to be the most efficacious. The goal of this study was to evaluate the efficacy and tolerability of a new, higher concentration of adapalene, adapalene 0.3% gel, compared to tazarotene 0.1% gel in the treatment of acne vulgaris. The primary efficacy outcome was the percent reduction in total lesion count at week 12. Subjects 12 to 35 years of age with acne vulgaris (N=172) participated in a 12-week, randomized, evaluator-blinded, noninferiority study of once-daily therapy with adapalene 0.3% gel or tazarotene 0.1% gel. Subjects in each group achieved clinically significant reductions in total lesion counts at week 12 (61% and 57% median reductions for adapalene and tazarotene, respectively); adapalene 0.3% gel was noninferior to tazarotene 0.1% gel (95% confidence interval [CI]: -5.2-9.6). The adapalene arm was also therapeutically similar to the tazarotene arm in terms of the percent reduction in inflammatory and noninflammatory lesion counts at week 12, as well as in the assessments of acne severity and improvement. Mean tolerability scores for erythema, dryness, scaling, and stinging/burning were consistently lower in the adapalene arm compared to patients treated with tazarotene (P<.014 at week 12, Cochran-Mantel-Haenszel [CMH] test). The worst score for any tolerability parameter in the treatment phase in the adapalene arm was less than 1 (mild). Adapalene was also associated with a lower incidence of treatment-related adverse events when compared to tazarotene (3.5% versus 14%, respectively). Once daily therapy with adapalene 0.3% gel provided similar efficacy (noninferior) to tazarotene 0.1% gel in the treatment of acne vulgaris, but demonstrated a superior tolerability profile.

There are numerous proposed but contested components involved in the pathophysiology of rosacea, including inflammatory mediators, reactive oxygen species (ROS) released by neutrophils, and microbial components. Ideal comprehensive rosacea management should address these components. Azelaic acid (AzA), a naturally occurring substance, has many proposed mechanisms of action--antimicrobial, anti-inflammatory/antioxidant, and keratinolytic--that address the proposed components of rosacea pathophysiology and has demonstrated efficacy in subtype 2 rosacea. In a roundtable discussion, information leaders discussed the pathophysiology of rosacea and other issues of importance to successful rosacea management, such as skin care regimens, quality of life (QOL), and compliance.

Azelaic acid (AzA) initially was released in a 20% cream formulation, which has been shown to be effective in the treatment of mild to moderate rosacea. Recently, a 15% gel formulation was developed that vastly improved the delivery of AzA and has been proven by multiple studies to be effective in the treatment of rosacea. We present studies that examine both of these formulations, first in comparison with their vehicles and then in contrast with other well-accepted topical treatments of rosacea, such as metronidazole cream and gel.

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 the efficacy 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; > or =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 > or =2 grades was considered a clinically relevant improvement., Results: Each of the 5 investigators rated photographs of 577 patients ( approximately 52% women, approximately 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 > or =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 < or = 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 < or = 0.001, < or =0.001, < or =0.001, and < or =0.01, respectively, vs vehicle [17%])., Conclusions: : The results of this study suggest that topical retinoid monotherapy can achieve clinically significant improvements in inflammatory acne.

Background: Rosacea is a common, chronic dermatosis for which safe and effective new treatment options are needed., Objective: The objective of these studies was to evaluate the efficacy, tolerability, and safety of a new formulation of 15% azelaic acid (15%) gel (AzA gel), for the topical treatment of moderate, papulopustular rosacea., Methods: Two multicenter, double-blind, randomized, parallel-group, vehicle-controlled studies were conducted using identical study designs, patient-selection criteria, and efficacy end points. Overall, 329 patients were enrolled in study 1 and 335 patients in study 2., Results: Both studies consistently demonstrated the superiority of AzA gel over vehicle in the topical treatment of moderate, papulopustular rosacea. AzA gel yielded statistically significantly higher reductions in mean inflammatory lesion count than vehicle: 58% versus 40%, study 1 (P =.0001); 51% versus 39%, study 2 (P =.0208). Significantly higher proportions of patients treated with AzA gel experienced improvement in erythema compared with vehicle gel: 44% versus 29%, study 1 (P =.0017); 46% versus 28%, study 2 (P =.0005). Using the investigator's global assessment, therapeutic success in terms of a clear, minimal, or mild final result was achieved in 61% and 62% of patients treated with AzA gel in studies 1 and 2, respectively, which was significantly superior to the result achieved with vehicle (40% and 48%, respectively) (P <.0001, study 1; P =.0127, study 2). No serious, treatment-related adverse events were reported., Conclusion: The results of these 2 controlled studies demonstrate that AzA gel, used twice daily, is an efficacious, safe, and well-tolerated topical treatment for moderate, papulopustular rosacea.

A prior meta-analysis of 5 randomized controlled trials indicates that adapalene gel 0.1% is as effective as tretinoin gel 0.025% against acne and has greater tolerability. To determine the tolerability and efficacy of adapalene gel 0.1% versus tretinoin microsphere gel 0.1% in 168 patients with acne vulgaris, we conducted a 12-week, multicenter, randomized, controlled, investigator-masked, parallel-group design study. Efficacy variables included noninflammatory, inflammatory, and total lesion counts; global grade; and global assessment of improvement in acne severity. Skin tolerability variables included erythema, desquamation (scaling), dryness, pruritus, and stinging/burning. Our results showed that the efficacy of adapalene gel 0.1% was comparable to that of tretinoin microsphere gel, and both treatments had similar onset of action. Cutaneous tolerability was noted in both groups, with scores significantly better with adapalene gel 0.1% than with tretinoin microsphere gel 0.1%, and significantly fewer treatment-related adverse events were reported with adapalene gel 0.1%.