A 15% Trichloroacetic Acid + 3% Glycolic Acid Chemical Peel Series Improves Appearance of Hand Lentigines: An Evaluator-Blinded, Split-Hand Prospective Trial.

BACKGROUND: Improving the appearance of lentigines on the hands is a key component to hand rejuvenation. Soft tissue fillers revolumize hands, but do not address pigmentary changes. OBJECTIVE: This study investigated the effiacy of a 15% trichloroacetic acid (TCA) + 3% glycolic acid (GA) combination peel in improvement of appearance of hand lentigines. METHODS: A prospective evaluator-blinded, split-hand study was performed using a 15% TCA + 3% GA peel to treat patients with hand lentigines. Subjects received a total of 3 treatments at 4-week intervals on 1 hand, with the other hand serving as an untreated control. Final photographs were taken 12 weeks after the last treatment. Two blinded board-certified dermatologists graded improvement in hand lentigines using a 5-point scale. RESULTS: Eighteen of 20 patients completed the study (90%). The mean age was 64.4 years (SE 1.6, range 51-71). The mean pain scores were 3.8 (SE 0.4) on a 10-point scale (1 = no pain, 10 = extremely painful). Blinded evaluators correctly identified the after-treatment photographs in 16 patients (88%). Physician and patient-graded mean improvement of lentigines was significant for treated versus control hands ( p < .01). No adverse events were noted. CONCLUSION: A series of three 15% TCA + 3% GA peels are effective and safe in the treatment of hand lentigines.

Low-Dose Acitretin for Secondary Prevention of Keratinocyte Carcinomas in Solid-Organ Transplant Recipients.

BACKGROUND: Keratinocyte carcinomas, particularly squamous cell carcinoma (SCC), occur more frequently and aggressively in solid-organ transplant recipients (SOTRs) than in the general population. Systemic retinoids are effective in secondary prevention of keratinocyte carcinomas in this population, but their use is limited by adverse effects including a rebound effect in cases of treatment discontinuation. OBJECTIVE: Our aim was to determine whether low-dose acitretin is efficient in the secondary prevention of keratinocyte carcinomas in SOTRs. METHODS: This retrospective case-crossover study was conducted at a specialized dermatology clinic for SOTRs in a large transplantation center in 2010-2017. Patients with at least 1 previous keratinocyte carcinoma who were treated with acitretin 10 mg/day for 2 years were included. The main outcome was the difference in the number of new keratinocyte carcinomas diagnosed during treatment compared to during the 2-year pretreatment period. RESULTS: The cohort included 34 SOTRs. A significant reduction in the mean number of new keratinocyte carcinomas during treatment relative to the pretreatment period was observed (1.7 vs. 3.6, -53% p = 0.002). Similar results were noted on analysis by tumor type, for both SCC and basal cell carcinoma. CONCLUSION: This study of SOTRs demonstrated positive results for low-dose acitretin as a chemoprevention of keratinocyte carcinomas in this population.

Acitretin-induced periungual pyogenic granulomas and review.

Periungual pyogenic granulomas are benign vascular tumors that present as painful, round, spontaneously bleeding lesions composed of rapidly proliferating capillaries and excess tissue. The vast majority of pyogenic granulomas are caused by physical trauma or infectious agents and they may resolve spontaneously. Herein, we highlight a very rare case of periungual pyogenic granulomas induced by the regularly prescribed oral retinoid acitretin during treatment for congenital palmoplantar keratoderma. This unique case showed that it is feasible to continue acitretin therapy in the presence of pyogenic granuloma development if proper dose reduction and topical therapies are utilized. The patient's lesions resolved within two weeks of this protocol's initiation and the pyogenic granulomas did not recur over the course of a six-month follow-up observation period. In addition, we performed a systematic review of the literature using PubMed databases for the clinical features and treatments in other reported acitretin-induced pyogenic granuloma cases; we compiled a comprehensive list of other prescription drugs known to cause pyogenic granulomas up-to-date.

Bilateral Systematised Epidermolytic Epidermal Nevus: A case report.

Verrucous epidermal nevi (VEN) are benign congenital hamartomas consisting of keratinocytes. Histological examination mostly exhibits hyperkeratosis, acanthosis, papillomatosis and, rarely, the features of epidermolytic hyperkeratosis (EHK). We report a case of a 6-year-old boy who presented at Aga Khan University Hospital, Karachi, Pakistan with bilaterally symmetrical linear epidermal nevi following Blaschko's lines and showing epidermolytic hyperkeratosis on histology. The patient was treated with topical keratolytics and emolients which led to considerable improvement. To the best of the authors' knowledge, this is the first report of VEN from Pakistan.

Topical Imiquimod for Lentigo Maligna: Survival Analysis of 103 Cases With 17 Years Follow-up.

Topical imiquimod 5% cream has been investigated as off-label primary or adjuvant treatment for melanoma in situ, lentigo maligna type (LM). Herein, we present the largest known case series of lentigo maligna treated with topical imiquimod, with up to 17 years of follow-up, and include a recurrence-free survival analysis. In this case series, 103 lesions were retrospectively evaluated for treatment response and recurrence following a course of topical imiquimod with or without tazarotene gel 0.1% pretreatment between January 1, 2002 and March 31, 2019, and prospectively followed through November 15, 2019. Over median follow-up of 5.1 years (mean = 6.2 years, S = 5.2 years, range, 0.08–17.1 years), including 29.1% LM with >10 years follow-up, we observed a response rate of 97.1% (100/103), with 8 local recurrences (8/100, 8.0%) developing at mean 2.9 years (SD: 2.7 years). Local recurrence was significantly associated with a history of failed excision (P= 0.001), <60 applications of imiquimod (P= 0.04) and partial clinical clearance (P= 0.0003). Recurrence-free survival analysis demonstrated significant risk-stratification for low and high-risk groups (P= 0.0001). Long term risk for recurrence showed significant differences among low- and high-risk cases, with low-risk cases demonstrating favorable long-term outcomes, comparable to conventional and staged surgery. Our observed low recurrence in a large case series with long-term follow-up suggests the efficacy of topical 5% imiquimod for LM and emphasizes the need for randomized control trials comparing imiquimod with, or as an adjunct to, surgical treatment. J Drugs Dermatol. 2021;20(3):346-348. doi:10.36849/JDD.5660.

Management of Difficult-to-Treat Warts: Traditional and New Approaches.

Warts are regularly treated by dermatologists, and while many respond readily to first-line treatments, others may represent a therapeutic challenge. Large, deep, numerous, and extensive warts; treatment-resistant lesions with higher risk for side effects, such as hypopigmentation; or patients unable to tolerate or comply with our treatment regimen, may need alternative treatment options. In this work we review the characteristics of select modalities that should be considered for difficult-to-treat warts. We discuss efficacy and tolerability data as well as practical features that can guide us to select the best treatment for every scenario. Novel approaches, still in an investigational phase, are also discussed to illustrate potential future directions of wart treatment.

The use of retinoic acid in association with microneedling in the treatment of epidermal melasma: efficacy and oxidative stress parameters.

This study aimed to evaluate the effectiveness of isolated treatment with retinoic acid and its combination with the microneedling technique in facial melasma, seeking to associate these results with possible oxidative damage. This is a blinded randomized clinical trial with 42 women with facial melasma (skin phototype I-IV), randomized into Group A (microneedling and 5% retinoic acid) or Group B (5% retinoic acid alone). Four procedures were applied with 15 days intervals (4 blood collections). Clinical improvement was assessed using the Melasma Area Severity Index (MASI). Serum oxidative stress levels were evaluated by protein oxidation (carbonyl), lipid peroxidation (TBARS) and sulfhydryl groups, as well as enzyme activities of superoxide dismutase (SOD) and catalase (CAT). The statistical analyzes were performed by generalized estimation equation (GEE). There was a reduction in MASI scale and TBARS levels in both groups over time (p < 0.05), with no difference between groups (p = 0.416). There was also a substantial increase in the carbonyl levels at 30 days (p = 0.002). The SOD activity decreased after 30 days, regardless of group (p < 0.001), which was maintained after 60 days. In Group A, there was a reduction in sulfhydryl levels at 60 days (p < 0.001). It is important to highlight that both groups demonstrated efficacy in the clinical improvement of melasma within at least 60 days, reducing the MASI score by almost 50%. However, microneedling with retinoic acid seems to be the worst treatment because there is a reduction in the non-enzymatic antioxidant defense, which is important to protect against oxidative stress.

Effects of Tazarotene 0.045% Lotion on Quality of Life in Patients With Moderate-to-Severe Acne.

BACKGROUND: In two phase 3 trials (NCT03168334, NCT03168321), participants with moderate-to-severe acne had significant symptom improvements after 12 weeks of treatment with tazarotene 0.045% lotion. Given the negative psychosocial effects of acne on patients, data from these studies were analyzed to evaluate quality of life in various subgroups. METHODS: Mean changes from baseline to week 12 in Acne-Specific Quality of Life (Acne-QoL) domain and item scores were analyzed in the pooled intent-to-treat (ITT) population and in participants who were categorized as follows: Evaluator's Global Severity Score (EGSS) score=3 (“moderate”) or score=4 (“severe”) at baseline; Acne-QoL total score ≥60 (better quality of life) or <60 (worse quality of life), based on the median score at baseline. Exploratory analyses based on sex and race were also performed. RESULTS: In the pooled ITT population (N=1614), Acne-QoL improvements were greater with tazarotene 0.045% lotion versus vehicle lotion, with significant differences in the acne symptoms domain, 3 acne symptom items, 2 self-perception items, 1 role-emotional item, and 1 role-social item (all P<0.05). Acne-QoL improvements with tazarotene 0.045% lotion were comparable between the EGSS subgroups. However, participants who self-reported worse quality of life at baseline (Acne-QoL total score <60) had notably greater improvements than those with better quality of life. Female and Black participants had greater Acne-QoL improvements than male and White participants. CONCLUSIONS: Participants treated with tazarotene 0.045% lotion had significant quality-of-life improvements. Clinician-rated symptom severity appeared to have a smaller effect on Acne-QoL outcomes than participants’ own assessments of quality of life. J Drugs Dermatol. 2020;19(11): doi:10.36849/JDD.2020.5457.

Imiquimod versus podophyllotoxin, with and without human papillomavirus vaccine, for anogenital warts: the HIPvac factorial RCT.

BACKGROUND: The comparative efficacy, and cost-effectiveness, of imiquimod or podophyllotoxin cream, either alone or in combination with the quadrivalent HPV vaccine (Gardasil®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) in the treatment and prevention of recurrence of anogenital warts is not known. OBJECTIVE: The objective was to compare the efficacy of imiquimod and podophyllotoxin creams to treat anogenital warts and to assess whether or not the addition of quadrivalent human papillomavirus vaccine increases wart clearance or prevention of recurrence. DESIGN: A randomised, controlled, multicentre, partially blinded factorial trial. Participants were randomised equally to four groups, combining either topical treatment with quadrivalent human papillomavirus vaccine or placebo. Randomisation was stratified by gender, a history of previous warts and human immunodeficiency virus status. There was an accompanying economic evaluation, conducted from the provider perspective over the trial duration. SETTING: The setting was 22 sexual health clinics in England and Wales. PARTICIPANTS: Participants were patients with a first or repeat episode of anogenital warts who had not been treated in the previous 3 months and had not previously received quadrivalent human papillomavirus vaccine. INTERVENTIONS: Participants were randomised to 5% imiquimod cream (Aldara®; Meda Pharmaceuticals, Takeley, UK) for up to 16 weeks or 0.15% podophyllotoxin cream (Warticon®; GlaxoSmithKlein plc, Brentford, UK) for 4 weeks, which was extended to up to 16 weeks if warts persisted. Participants were simultaneously randomised to quadrivalent human papillomavirus vaccine (Gardasil) or saline control at 0, 8 and 24 weeks. Cryotherapy was permitted after week 4 at the discretion of the investigator. MAIN OUTCOME MEASURES: The main outcome measures were a combined primary outcome of wart clearance at week 16 and remaining wart free at week 48. Efficacy analysis was by logistic regression with multiple imputation for missing follow-up values; economic evaluation considered the costs per quality-adjusted life-year. RESULTS: A total of 503 participants were enrolled and attended at least one follow-up visit. The mean age was 31 years, 66% of participants were male (24% of males were men who have sex with men), 50% had a previous history of warts and 2% were living with human immunodeficiency virus. For the primary outcome, the adjusted odds ratio for imiquimod cream versus podophyllotoxin cream was 0.81 (95% confidence interval 0.54 to 1.23), and for quadrivalent human papillomavirus vaccine versus placebo, the adjusted odds ratio was 1.46 (95% confidence interval 0.97 to 2.20). For the components of the primary outcome, the adjusted odds ratio for wart free at week 16 for imiquimod versus podophyllotoxin was 0.77 (95% confidence interval 0.52 to 1.14) and for quadrivalent human papillomavirus vaccine versus placebo was 1.30 (95% confidence interval 0.89 to 1.91). The adjusted odds ratio for remaining wart free at 48 weeks (in those who were wart free at week 16) for imiquimod versus podophyllotoxin was 0.98 (95% confidence interval 0.54 to 1.78) and for quadrivalent human papillomavirus vaccine versus placebo was 1.39 (95% confidence interval 0.73 to 2.63). Podophyllotoxin plus quadrivalent human papillomavirus vaccine had inconclusive cost-effectiveness compared with podophyllotoxin alone. LIMITATIONS: Hepatitis A vaccine as control was replaced by a saline placebo in a non-identical syringe, administered by someone outside the research team, for logistical reasons. Sample size was reduced from 1000 to 500 because of slow recruitment and other delays. CONCLUSIONS: A benefit of the vaccine was not demonstrated in this trial. The odds of clearance at week 16 and remaining clear at week 48 were 46% higher with vaccine, and consistent effects were seen for both wart clearance and recurrence separately, but these differences were not statistically significant. Imiquimod and podophyllotoxin creams had similar efficacy for wart clearance, but with a wide confidence interval. The trial results do not support earlier evidence of a lower recurrence with use of imiquimod than with use of podophyllotoxin. Podophyllotoxin without quadrivalent human papillomavirus vaccine is the most cost-effective strategy at the current vaccine list price. A further larger trial is needed to definitively investigate the effect of the vaccine; studies of the immune response in vaccine recipients are needed to investigate the mechanism of action. TRIAL REGISTRATION: Current Controlled Trials. Current Controlled Trials ISRCTN32729817 and EudraCT 2013-002951-14. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 47. See the NIHR Journals Library website for further project information.

The HIPvac [Human papillomavirus infection: a randomised controlled trial of Imiquimod cream (5%) versus Podophyllotoxin cream (0.15%), in combination with quadrivalent human papillomavirus or control vaccination in the treatment and prevention of recurrence of anogenital warts] trial compared two commonly used creams to treat genital warts: 0.15% podophyllotoxin cream (Warticon^®; GlaxoSmithKlein plc, Brentford, UK) and 5% imiquimod cream (Aldara^®; Meda Pharmaceuticals, Takeley, UK). It also investigated whether or not a vaccine used to prevent human papillomavirus infection, quadrivalent human papillomavirus vaccine (Gardasil^®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA), could help treat warts or prevent them from coming back in patients whose warts had been cleared. The HIPvac trial was a randomised controlled trial involving 503 patients with warts attending sexual health clinics in England and Wales. The creams and the vaccine were well tolerated; there was some soreness where the cream was applied, but no unexpected side effects. When deciding which treatment was better, we looked at whether or not the warts had cleared by 16 weeks after starting treatment and, if cleared, whether or not they returned by 48 weeks. We compared the creams against each other, and the addition of vaccine against no vaccine (a placebo injection). Patients were allowed to have cryotherapy (freezing treatment) as well, if the investigator advised this. We also calculated the value for money of each type of treatment. The two creams were very similar in how well they worked to clear the warts. One difference was that podophyllotoxin cream worked slightly quicker. The number of patients given cryotherapy was about the same for both types of cream. We had expected that recurrence of warts after treatment with imiquimod cream might be less than after treatment with podophyllotoxin cream, but, in fact, the two creams were similar. Quadrivalent human papillomavirus vaccine did not improve clearance of warts or reduce the chance of recurrence, but the result remains inconclusive. If we had been able to recuit 1000 participants as originally planned, we might have been able to be more certain about whether there was any benefit of vaccination. Further research would be needed to investigate any possible effect. The two creams offered similar value for money in treating warts. Giving patients the vaccine in addition to the cream is not good value for money at its current list price, given the uncertainty about the benefit it offers.

Comparative effectiveness of different therapies for treating striae distensae: A systematic review and network meta-analysis.

BACKGROUND: Striae distensae (SD) are common and aesthetically undesirable dermal lesions. The aim of this study is to comprehensively evaluate the effectiveness of different therapies in treating striae distensae using network meta-analysis. METHODS: A systematic search of electronic databases up to December 1, 2019 was conducted. Randomized controlled trails (RCTs) examining the effectiveness of different methods in treating striae distensae were included. The primary outcomes are clinical effective rate and patient's satisfaction degree. Risk of bias was assessed by the Cochrane risk of bias tool. Network meta-analysis was based on Bayesian framework. RESULTS: Fourteen trails that met the criteria with 651 subjects were included. The results of the network meta-analysis show that topical tretinoin combined bipolar radiofrequency showed the highest probability of being the best method to improve the clinical effectiveness and patient satisfaction rate of treating SD (84.5% and 95.7% respectively), closely followed by bipolar radiofrequency (75.3% and 84.3% respectively). Among laser treatment, CO2 fractional laser is superior to other lasers in the clinical effectiveness and patient satisfaction (72.0% and 58.1% respectively). Statistics showed the topical tretinoin was the worst-performing option in improving the clinical effectiveness and patient satisfaction rate of SD treatment (5.4% and 5.1% respectively). CONCLUSION: Based on the results of network meta-analysis, we recommend treating striae distensae with bipolar radio frequency combined topical tretinoin. The commonly used CO2 fractional laser can be considered as alternative treatment candidate. Additional large-scale RCTs are necessary to obtain more precise estimates of their relative efficacy.

The Effects of Once-Daily Tretinoin 0.05% Lotion on Quality of Life in Patients with Moderate-to-Severe Acne Vulgaris.

BACKGROUND: In two phase III clinical trials of patients with moderate-to-severe acne (NCT02932306, NCT02965456), tretinoin 0.05% lotion reduced inflammatory and noninflammatory lesions relative to vehicle lotion, with low potential for cutaneous irritation. OBJECTIVE: Data from these studies were analyzed post hoc to investigate the effects of tretinoin 0.05% lotion on patient-reported quality of life, as assessed using the Acne-Specific Quality of Life Questionnaire (Acne-QoL). METHODS: Mean changes from baseline to week 12 in Acne-QoL scores were analyzed in the pooled intent-to-treat population and a subgroup with treatment success (≥ 2-grade improvement on the Evaluator's Global Severity Scale and rating of "clear" or "almost clear"). Pearson correlations were conducted in the pooled intent-to-treat population to assess the relationship between the Acne-QoL acne symptoms domain and each of the other three domains. RESULTS: In the pooled intent-to-treat population (n = 1640), greater mean improvements were found with tretinoin 0.05% lotion vs vehicle in all four domains: self-perception (mean change: 7.4 vs 6.7); role-emotional (6.8 vs 6.0); role-social (4.8 vs 4.6); acne symptoms (6.5 vs 5.6); all p < 0.05. Relative to the intent-to-treat population, participants who experienced treatment success with tretinoin 0.05% lotion had higher (better) mean Acne-QoL scores at week 12. Correlations between acne symptoms and the other three domains were found at baseline and week 12 (p < 0.05). CONCLUSIONS: Participants with moderate-to-severe acne reported better quality of life after 12 weeks of treatment with tretinoin 0.05% lotion. Clinical improvements in acne symptoms may have contributed to these outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02932306, NCT02965456.

Once-Daily Polymeric Tazarotene 0.045% Lotion for Moderate-to-Severe Acne: Pooled Phase 3 Analysis by Sex.

Background: Two identical phase 3 randomized, double-blind, vehicle-controlled, 12-week studies (NCT03168321 and NCT03168334) demonstrated the efficacy and safety of tazarotene 0.045% lotion in participants with moderate-to-severe acne. Data from these studies were pooled and analyzed post hoc to evaluate outcomes by sex. Methods: Patients aged ≥9 years with moderate-to-severe acne (score 3 or 4 on the Evaluator's Global Severity Score [EGSS]) were randomized (1:1) to once-daily tazarotene 0.045% lotion or vehicle lotion for 12 weeks. Outcomes comprised inflammatory/noninflammatory lesion counts, treatment success (proportion of participants achieving ≥2-grade reduction from baseline in EGSS and score of 0 ["clear"] or 1 ["almost clear"]), and treatment-emergent adverse events (TEAEs). Results: A total of 1,064 females and 550 males were included in this analysis. For both sexes, least-squares mean percent changes from baseline to week 12 in lesion counts were significantly greater with tazarotene 0.045% lotion versus vehicle (inflammatory: females, -60.1% vs -52.1%; males, -53.6% vs -39.8%; noninflammatory: females, -57.6% vs -44.9%; males, -52.9% vs -36.5%; P<0.001, all). The percentage of participants achieving treatment success at week 12 was also significantly higher with tazarotene 0.045% lotion versus vehicle in females and males (P<0.001, both). Compared with tazarotene-treated males, tazarotene-treated females had significantly greater changes from baseline in inflammatory and noninflammatory lesions and a greater proportion achieved treatment success at week 12 (P<0.05, all). TEAE rates were similar between tazarotene- and vehicle-treated males; rates were higher for tazarotene-treated females than vehicle-treated females. Conclusions: Tazarotene 0.045% lotion was efficacious and well tolerated in the treatment of moderate-to-severe acne in female and male participants. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5249

Post-Inflammatory Hyperpigmentation: A Review of Treatment Strategies.

Post-inflammatory hyperpigmentation (PIH) is a reactive process resulting from increased melanin or abnormal distribution of melanin secondary to inflammatory skin conditions, dermatologic therapies, and external stimuli. Because PIH is a common condition that has a substantial effect on the quality of life, an understanding of its treatment modalities is essential. Though there are many therapeutic strategies for hyperpigmentary conditions such as melasma that are described in the literature, fewer studies focus on PIH. This article aims to provide a comprehensive literature review of therapies specifically used to treat PIH, such as topical combinations, chemical peels, and lasers. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.4887.

Case Report: Treatment of Chromoblastomycosis with Combinations including Acitretin: A Report of Two Cases.

Chromoblastomycosis is a cutaneous fungal infection caused by dematiaceous fungi that belong to the order Chaetothyriales and family Herpotrichiellaceae. This infection is prevalent in tropical and subtropical areas and has been designated as a neglected tropical disease according to the WHO. Chromoblastomycosis infection is difficult to treat, and there are limited therapeutic options, making urgent the characterization of new medicines or approaches to treat such infection. In the present case report, two patients with extensive chromoblastomycosis lesions were treated with the combination of itraconazole, acitretin, and imiquimod. In the fourth month of treatment, both patients showed improvement of verrucous plates, suggesting that acitretin combined with drugs already used in chromoblastomycosis therapy can decrease the time of treatment, improving patient's quality of life.

Novel Polymeric Tazarotene 0.045% Lotion for Moderate-to-Severe Acne: Pooled Phase 3 Analysis by Race/Ethnicity.

Background: Acne vulgaris and inflammation-associated sequelae are highly prevalent in black and Hispanic populations. In a phase 2 study, a novel polymeric emulsion formulation of tazarotene 0.045% lotion had relatively fewer adverse events than tazarotene 0.1% cream, but with comparable efficacy. The objective was to evaluate tazarotene 0.045% lotion by race and ethnicity in the pivotal trials. Methods: In two phase 3, double-blind, 12-week studies (NCT03168334; NCT03168321), participants with moderate-to-severe acne were randomized 1:1 to tazarotene 0.045% lotion or vehicle lotion (N=1,614). This pooled, post hoc analysis included subsets of participants that self-identified as white (n=1191) or black (n=262) and Hispanic (n=352) or non-Hispanic (n=1262). Coprimary endpoints were inflammatory/noninflammatory lesion counts and treatment success (defined as at least a 2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 'clear' or 'almost clear'). Treatment-emergent adverse events (TEAEs) and cutaneous safety and tolerability were evaluated. Results: At week 12, tazarotene 0.045% lotion led to significantly greater percent reductions in inflammatory and noninflammatory lesions compared with vehicle in white, Hispanic, and non-Hispanic participants (P<0.05, all). Black participants had significantly greater reductions in noninflammatory lesions following treatment with tazarotene 0.045% versus vehicle (P<0.05). Treatment success rates in all subpopulations were higher with tazarotene 0.045% lotion (29.4-34.1%) versus vehicle (16.4-23.1%). TEAE rates were similar across tazarotene-treated groups and most were mild-to-moderate in severity. The incidence of hyperpigmentation decreased in black tazarotene-treated participants from baseline to week 12. Conclusions: Tazarotene 0.045% lotion demonstrated efficacy and was well tolerated across racial and ethnic subpopulations in this pooled analysis. J Drugs Dermatol. 2020;19(7) doi:10.36849/JDD.2020.5125.

New Polymeric Once-Daily Tazarotene 0.045% Lotion Formulation for Moderate-to-Severe Acne: Pooled Phase 3 Pediatric Analysis.

BACKGROUND: Acne vulgaris affects approximately 85% of adolescents. Topical tazarotene is efficacious and safe for acne treatment but irritation limits its use. The objective was to evaluate efficacy, safety, and tolerability of a new tazarotene 0.045% lotion formulation in patients aged 10-13 and 14-17 years with moderate-to-severe acne. METHODS: In two phase 3, double-blind, vehicle-controlled 12-week studies, patients with moderate-to-severe acne (N=1,614) were randomized (1:1) to receive tazarotene 0.045% lotion or vehicle once-daily. Efficacy assessments included changes from baseline in inflammatory/noninflammatory lesions and treatment success (≥2-grade reduction in Evaluator's Global Severity Score [EGSS] and a clear/almost clear score). Quality of life (QoL) and adverse events (AEs) were also assessed. RESULTS: Patients aged 10-13 years (n=136) and 14-17 years (n=548) were pooled. At week 12, mean percent reductions in inflammatory and noninflammatory lesion counts were significantly greater with tazarotene versus vehicle in both age groups (least-squares mean inflammatory 10-13 years: -55.6 vs -37.0%; 14-17 years: -53.3 vs -41.2%; noninflammatory 10-13 years: -47.7 vs -28.2%; 14-17 years: -52.7 vs -32.9%; P<0.01 all). More patients achieved treatment success with tazarotene versus vehicle in both age groups (P<0.05, both). There were no significant differences between tazarotene-treated age groups in lesion counts or treatment success. Acne-QoL scores at week 12 in both age groups were numerically improved in most domains with tazarotene 0.045% lotion versus vehicle. Most treatment-emergent AEs with tazarotene or vehicle were of mild or moderate severity in both age groups. CONCLUSIONS: Tazarotene 0.045% lotion was efficacious and well tolerated in pediatric patients with moderate-to-severe acne. J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.4959.

Novel Polymeric Lotion Formulation of Once-Daily Tazarotene (0.045%) for Moderate-to-Severe Acne: Pooled Phase 3 Analysis.

Background: As current tazarotene formulations indicated for acne (0.1%) can cause irritation, a new tazarotene 0.045% lotion formu-lation was developed using polymeric emulsion technology. The objective was to assess efficacy, safety, and tolerability of tazarotene 0.045% lotion in patients with moderate-to-severe acne in a pooled analysis of data from two identical phase 3, double-blind, random-ized, vehicle-controlled 12-week clinical studies. Methods: Patients aged ≥9 years with moderate-to-severe acne were randomized (1:1) to tazarotene 0.045% lotion or vehicle lotion applied once daily. Inflammatory and noninflammatory lesion counts and Evaluator's Global Severity Score (EGSS) were assessed. Treatment success was defined as a ≥2-grade improvement in EGSS and a score of 'clear'/'almost clear'. Adverse events (AEs) and cutaneous safety and tolerability were also assessed. Results: In total, 1614 patients (mean age: 20.5 years) were randomized to tazarotene 0.045% lotion (n=799) or vehicle (n=815). At week 12, tazarotene 0.045% lotion demonstrated statistically significant superiority versus vehicle in reducing inflammatory and non-inflammatory lesion counts (least-squares mean percent changes from baseline: inflammatory, -57.9% vs -47.8% [P<0.001]; noninflam-matory, -56.0% vs -42.0% [P<0.001]). Treatment success at week 12 was also greater with tazarotene 0.045% lotion versus vehicle (30.4% vs 17.9%; P<0.001). The most frequent treatment-emergent AEs related to tazarotene treatment were application site pain (5.3%), dryness (3.6%), and exfoliation (2.1%). Conclusions: The new tazarotene 0.045% lotion formulated with polymeric emulsion technology demonstrated statistically signifi-cantly superior efficacy versus vehicle and was well tolerated in pediatric and adult patients with moderate-to-severe acne in this pooled analysis of 2 vehicle-controlled phase 3 studies. J Drugs Dermatol. 2020;19(3):272-279. doi:10.36849/JDD.2020.4869.

Hypertrophic lichenoid dermatitis immune-related adverse event during combined immune checkpoint and exportin inhibitor therapy: A diagnostic pitfall for superficially invasive squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) for cancer treatment have revolutionized the field of medicine. However, an unintended but frequent consequence of ICI therapy is the development of cutaneous immune-related adverse events (irAEs), such as lichenoid dermatitis irAEs (LD-irAEs). The hypertrophic variant of LD-irAE may be a diagnostic challenge since it can mimic superficially invasive squamous cell carcinoma (SCC). A 79-year-old woman with metastatic melanoma who began treatment with an ICI-pembrolizumab-plus exportin-1 (XPO1) inhibitor presented after 1 month of therapy with symmetrical violaceous papules coalescing into plaques and with two nodules of the bilateral dorsal hands. Biopsy of the nodules revealed an actinic keratosis and atypical epidermal proliferation concerning for SCC. However, in the ensuing 3 weeks, the patient developed multiple new erythematous, violaceous, and scaly macules and papules, some coalescing into plaques on the extremities. Biopsies of these lesions revealed exuberant irregular epidermal hyperplasia with hypermaturation and lichenoid infiltrate concentrated at the base of the elongated, broadened rete ridges, consistent with hypertrophic LD-irAE. Treatment included topical fluocinonide ointment, intralesional triamcinolone injections and oral acitretin. Distinguishing hypertrophic LD-irAE and SCC can be challenging since both entities share histopathologic features; thus, correlation with clinical presentation is essential for diagnosis and optimal patient management.