Acne Conference Coverage 2022: Poster Highlights
ANTIBIOTIC STEWARDSHIP AND ADVANCES IN ANTIBIOTICS FOR ACNE Antibiotic stewardship (i.e., the right dose of the right antibiotic at the right time for the right duration) was a particularly hot topic at many dermatology meetings in 2022. Research on trends in antibiotic stewardship and data on new narrow-spectrum antibiotics that will decrease the risk of antibiotic resistance were presented across several meetings. An Expert Panel Questionnaire for Assessing Patient-reported and Caregiver-reported Outcomes in Acne Vulgaris Although acne has been shown to negatively affect patient quality of life, functioning, and psychosocial factors, current patient-reported outcome (PRO) tools do not sufficiently evaluate the impact of acne on patients. As such, Baldwin et al1 created an expert panel questionnaire (EPQ) containing acne-specific PRO and caregiver-reported measures to assess disease impact and patient experience in acne and improve outcomes. A 10-person consensus panel identified 11 PROs to complement the Acne Symptom and Impact Scale (ASIS) and were determined as optimal for use in community-based, real-world research. The 11 items in the EPQ encompass emotional functioning, social functioning, activities of daily living (ADL), and perspectives of parents/caregivers. Impact of Acne on Social Functioning, Emotional Functioning, and Activities of Daily Living Among Patients with Moderate to Severe Non-nodular Acne Vulgaris Administered Sarecycline in Real-world Community Practices Across the United States Here, Fried et al2 utilized a novel EPQ to assess the impact of acne on emotional functioning, social functioning, and ADL among patients with moderate-to-severe non-nodular acne receiving sarecycline. At Week 12, there was a significant improvement in patients reporting “never/rarely” or “not at all/slightly/a little” for 10 of 11 EPQ items, indicating a significant reduction of acne burden among patients. The proportion of patients reporting a high acne burden significantly decreased at Week 12 as well. Thus, treatment with sarecycline was associated with improved emotional functioning, social functioning, and ADL in patients with acne. Patient Reported Outcomes and Investigator Global Assessment of Acne Vulgaris Among Patients with Moderate to Severe Non-nodular Acne Vulgaris Administered Sarecycline in Real-world Community Practices Across the United States In this study, Graber et al3 assessed PROs using ASIS and Investigator Global Assessment (IGA) scores among patients with moderate-to-severe non-nodular acne receiving sarecycline. At Week 12, 58.9 percent of patients achieved clear or almost clear skin (IGA score: 0/1). Additionally, only 11.1 percent of patients had moderate-to-severe acne at Week 12. Mean ASIS scores decreased significantly from baseline to Week 12, indicating improvements in acne symptoms and emotional/social impact. Additionally, 88.1 percent of patients reported satisfaction with sarecycline treatment outcomes at Week 12. Determinants of Antibiotic Stewardship for Acne: A Pilot Survey of Key Stakeholders Case et al4 conducted research evaluating determinants of antibiotic stewardship. In this study, researchers surveyed 30 key stakeholders including 22 dermatologists, four infectious diseases specialists, two dermatology advanced practice providers, and two dermatology residents. Influences on antibiotic prescribing practices were quantified using the validated 23-item “Influences on Patient Safety Behaviors Questionnaire” (IPSBQ). IPSBQ scores were summarized descriptively. Participants were 53-percent female. 73.3 percent identified as non-Hispanic White, 20 percent non-Hispanic Asian, 3.3 percent non-Hispanic Black, and 3.3 percent Hispanic. Participants had practiced for an average of 15.1 (SD,13.4) years. Factors reflecting highest barriers to antibiotic stewardship included “social influence”, “beliefs about capabilities”, “memory, attention, and decision processes”, and “environmental context and resources” with mean IPSBQ domain scores (SD) of 3.28 (0.79), 3.21 (1.09), 2.9 (0.93) and 2.67 (1.01), respectively. Management of Truncal Acne with Oral Sarecycline: Pooled Results from Two Phase III Clinical Trials Truncal acne is present in at least 50 percent of patients with acne, but clinical studies have predominately focused on facial acne. Del Rosso et al5 evaluated oral sarecycline for the treatment of truncal acne in two Phase III clinical trials using Investigator Global Assessment (IGA) success evaluated at Weeks 3, 6, 9, and 12. After conducting this study, chest IGA success rates showed significant improvement with sarecycline versus placebo comparing results at Week 3 (11.84% vs. 7.71%, respectively; p=0.0192) versus Week 12. (33.42% vs. 20.77%, respectively; p<0.0001 IGA success rates on the back also showed significant improvement with sarecycline versus placebo group at Week 3 (12.13% vs. 7.04%, respectively; p=0.0023), compared to Week 12 (33.07% vs. 21.91%, respectively; p<0.0001). Trends in Oral Antibiotic Use for Acne Treatment: A Population-based Study in the United States, 2014–2016 Grada et al6 evaluated trends in oral antibiotic use for the treatment of acne vulgaris in a population-based study. Patients included in this study were at least nine years of age or older, prescribed an oral antibiotic, and had two or more diagnoses of acne seven or more days apart. Across all patients, the most commonly prescribed antibiotics were doxycycline and minocycline; 73.4%, 11.4%, 4.1%, and 10.9% of patients were prescribed tetracycline-class antibiotics, penicillin, macrolides, and another antibiotic class. Overall, 36.3 percent, 17.6 percent, 10.3 percent, and 5.4 percent of patients continuously used any oral antibiotic at 3, 6, 9, and 12 months. In this retrospective study, researchers discovered approximately 20 percent of patients used oral antibiotics for six months or greater. Based on these results, authors concluded that there is opportunity to reduce the rate of antibiotic resistance and antibiotic-associated complications by considering alternative treatments such as narrow-spectrum oral antibiotics, hormonal therapy, earlier initiation of isotretinoin, and laser and light-based modalities. Efficacy of Oral Sarecycline in Hispanic Patients with Facial Inflammatory Acne Moore et al7 conducted a subgroup analysis from two Phase III trials that evaluated over 500 Hispanic patients in hopes of better understanding the efficacy of oral sarecycline for facial inflammatory acne. Sarecycline, an FDA-approved treatment for moderate-to-severe acne for patients nine years or older, was evaluated in this study. Over 2,000 subjects were randomized to receive oral sarecycline at 1.5 mg/kg/day or placebo. Researchers found that in Hispanic patients, facial inflammatory lesions decreased at Week 6 by 41 percent versus 30 percent, at Week 9 by 51 percent versus 38 percent, and at Week 12 by 55 percent versus 37 percent in patients on sarecycline
Assessment of Photodynamic Therapy Services Performed Among Medicare Beneficiaries from 2018 to 2019
J Clin Aesthet Dermatol. 2022;15(11):37–39. by Christian Gronbeck, MD* and Ashley M. Hine, BS*; Jeffrey M. Cohen, MD; and Hao Feng MD, MHS *Dr. Gronbeck and Ms. Hine share co-first authorship on this article. Ms. Hine is with the University of Connecticut School of Medicine in Farmington, Connecticut. Drs. Gronbeck and Feng are with Department of Dermatology at University of Connecticut Health Center in Farmington, Connecticut. Dr. Cohen is with the Department of Dermatology at Yale University School of Medicine in New Haven, Connecticut. FUNDING: No funding was provided for this article. DISCLOSURES: Dr. Feng is a consultant at Cytrellis Biosystems, Inc and Soliton Inc. ABSTRACT: Objective. Photodynamic therapy (PDT) is a useful treatment modality for premalignant skin lesions. We sought to describe PDT utilization on a national level in the Medicare population post-CPT code revision in 2018 to better understand trends in volume and distribution as well as what factors may influence service performance. Methods. We used the 2018–2019 Medicare Physician and Other Supplier Public Use File to assess PDT services performed during this period. Results. We found that there was an increasing trend of PDT utilization in the Medicare population. While there was less PDT performed without direct involvement of a healthcare professional, an increasing number of PDT services requiring debridement were performed for severe lesions. Although the majority of PDT volume was attributable to dermatologists, non-physician clinicians assumed greater involvement in PDT services. Dermatologists practicing in academic and non-metropolitan settings were less likely to be directly involved with PDT delivery. Conclusion. There is a considerable volume of PDT performed among Medicare beneficiaries, with several utilization trends that may be explained by geographic location and practice setting, among other factors. These findings provide insight to PDT service distribution on a national level and highlight practice patterns that may influence PDT delivery. Keywords: Photodynamic therapy, dermatology, debridement, non-physician clinicians, Medicare Photodynamic therapy (PDT) is a field-directed therapy for premalignant actinic keratoses and is an effective treatment modality for certain superficial keratinocytic carcinomas (KCs).1 Despite its increasing utilization in the Medicare population2, the volume and distribution of PDT services performed by dermatologists and other providers have not been characterized since the implementation of revised Current Procedural Terminology (CPT) codes in 2018, which now capture direct healthcare professional involvement in PDT delivery as well as any preceding debridement.3 Methods We analyzed the 2018–2019 Medicare Physician and Other Supplier datasets to describe the overall volume and relative proportion of PDT services performed with and without direct involvement of a healthcare professional (e.g., dermatologist, non-physician clinician [NPC]), and with preceding debridement.4 We summarized aggregate utilization statistics and also stratified our assessment across specific subsets of dermatologists and NPCs. We further assessed the relative utilization of each PDT service type at the state level. Results Across all providers, 152,310 PDT procedures were performed in 2019, representing an increase of 5.9 percent from 2018. Geographically, total PDT volume was highest in the Pacific, Mountain, and South Atlantic states (Figure 1). The proportion of PDT services performed without direct involvement of a healthcare professional decreased from 55.7 percent to 43.9 percent in 2019, primarily due to a significant increase in PDT services requiring preceding debridement (Table 1). Discussion These findings support increasing healthcare professional direct involvement in delivery of PDT, primarily in cases with more severe premalignant lesions requiring debridement. However, regions with classically high sun exposure and overall greater PDT volume (South, Pacific) exemplified a relatively high proportion of services performed without direct physician involvement, which might be due to physician time constraints relative to demand, challenges in changing existing processes directed by other office staff, or lack of knowledge regarding CPT code changes. Dermatologists still billed for the vast majority of PDT services in 2019, although independently-billing NPCs assumed a growing role over the study period, including more direct involvement in PDT relative to dermatologists and in cases requiring debridement. Dermatologists in non-metropolitan regions were less likely to be directly involved with PDT services in their clinics, which could be related to the lower density of dermatologists and other providers in these regions.2 The frequent direct involvement in PDT by solo practice dermatologists may be explained by fewer resources and ancillary staff capable of delivering PDT at these practices. By comparison, continuing medical education and training activities at academic centers may foster PDT proficiency among office staff, potentially enabling less frequent direct involvement exhibited by dermatologists in these settings. Limitations. This analysis has several limitations. Findings from Medicare data may not be generalizable to patients with commercial insurance. Furthermore, providers performing fewer than 11 annual PDT procedures are excluded, leading to slight underestimations at the provider (not aggregate) level. Nevertheless, this study supports an increasing trend in PDT services and provides greater insight into PDT service distribution among Medicare beneficiaries. Further studies assessing the reasons for these practice patterns are warranted. References Ozog DM, Rkein AM, Fabi SG, et al. Photodynamic Therapy: A Clinical Consensus Guide. Dermatol Surg. 2016;42(7):804–827. Cheraghlou S, Feng H, Cohen JM. Trends in the Access and Cost of Photodynamic Therapy Among Medicare Beneficiaries in the United States, 2012-2017. JAMA Dermatol. Sep 1 2020;156(9):1021–1022. Siegel DM. Let there be light: update on coding for photodynamic therapy and lasers. Cutis. Mar 2018;101(3):180–182. Centers for Medicare and Medicaid Services. Medicare Physician & Other Practitioners – by Provider and Service. Accessed September 29, 2021. https://data.cms.gov/provider-summary-by-type-of-service/medicare-physician-other-practitioners/medicare-physician-other-practitioners-by-provider-and-service.
Oral Zinc as a Novel Adjuvant and Sparing Therapy for Systemic Isotretinoin in Acne Vulgaris: A Preliminary Comparative Study
J Clin Aesthet Dermatol. 2022;15(10):58–61. Dr. Salah is an Assistant Professor of Dermatology, Venereology and Andrology at Zagazig University in Zagazig, Egypt by Eman Salah, PhD FUNDING: No funding was provided for this article. DISCLOSURES: The author reports no conflicts of interest relevant to the content of this article. ABSTRACT: Background. Systemic isotretinoin is the most effective treatment for acne vulgaris (AV). However, numerous side effects are associated with isotretinoin. Oral zinc has a better safety profile and has been used to treat AV with variable results. Objective. We sought to evaluate the safety and efficacy of combining oral zinc to low-dose systemic isotretinoin in AV patients. Methods. Sixty AV patients were divided into two groups. Group A received oral zinc sulfate plus low-dose isotretinoin and Group B received the standard isotretinoin dosage. At each visit acne severity, photos, side effects, and patient-reported satisfaction were recorded. Results. In the two groups, no significant difference in reduction of lesion count and Global Acne Grading System scores. The frequency of treatment-related side effects was (20%) in Group A and (76.7%) in Group B. Furthermore, there was no difference regarding the relapse rates between both groups (p>0.05). Finally, the patients’ satisfaction rates did not differ between the two groups. Conclusion. Oral zinc plus low-dose isotretinoin resulted in satisfactory improvement in AV patients with fewer side effects. Further studies are recommended to compare the efficacy of other zinc preparations if combined with systemic isotretinoin at different concentrations. Keywords. Acne vulgaris, zinc, isotretinoin, sebaceous glands. Zinc is an essential trace element that performs catalytic, structural, and regulatory functions in different cells including keratinocytes. Zinc abnormalities have been incriminated in acne vulgaris (AV) due to its anti-inflammatory, anti-bacterial and anti-androgenic effects.1 Therefore, different zinc preparations have been used successfully to treat AV. Systemic isotretinoin, a vitamin A analog, is the most effective treatment for AV but comes with numerous side effects1–4 that may mimic zinc deficiency.5 Interestingly, zinc can affect the absorption, transportation, and utilization of vitamin A.6 Here, we compared the efficacy and safety of oral zinc and low-dose isotretinoin combination versus standard-dose isotretinoin monotherapy in moderate to severe AV. Methods Ethical approvals. The Institutional Review Board approved this work in accordance with the Declaration of Helsinki. Before enrollment, all subjects provided a well-informed and written consent. Patients. This study included 60 patients with moderate-to-severe AV according to the global acne grading system (GAGS).7 Two blinded independent investigators evaluated the patients for enrollment and follow-up. Serum zinc was measured to exclude zinc deficiency. Before initiating isotretinoin, regular laboratory workup was performed, and lesions were counted with photo-documentation. A software program was used to randomly assign a patient in 1 of 2 groups. Group A, the “experimental group”; who received low-dose isotretinoin (0.25mg/kg/d) and oral zinc sulfate (each 110mg zinc sulfate per capsule yields 25mg of elemental zinc) at a dose of (1mg/kg/d) while Group B, the “control group”; was maintained on standard-dose of (0.5mg/kg/d) isotretinoin. Included patients were males and females at aged at least 15 years and with moderate to severe AV, absent contraindications for isotretinoin or zinc sulfate and a two-week washout period for topical or four weeks for systemic acne therapies. Exclusion criteria were pregnancy, lactation, low serum zinc, and patients who reported interruptions of therapy or did not follow the scheduled monitoring visits were excluded. All patients were evaluated at baseline and monthly for five months evaluating lesions count, GAGS, and possible side effects. At the fifth follow-up visit patients rated their satisfaction level with the used treatment. Finally, all patients were observed for six months after completion of the treatment course to report possible early relapses. Furthermore, the patients were scheduled for a long-term follow up with a maximum of two years to detect any future late relapses. Statistical analysis. Quantitative data were expressed as the mean ± SD and median (range), and qualitative data were expressed as absolute frequencies (number) and relative frequencies (percentage). Continuous data were checked for normality by using the Shapiro Walk test. The Mann Whitney U test was used to compare two groups of non-normally distributed data. Friedman’s test was used to compare between more than two dependent groups of non-normally distributed data. Wilcoxon signed rank test was used to compare between two dependent groups of non-normally distributed data. Categorical data were compared using the Chi-square test or Fisher’s exact test when appropriate. All tests were two-sided. P-value <0.05 was considered statistically significant. All data were collected, tabulated, and statistically analyzed using SPSS 20.0 for Windows (SPSS Inc., Chicago, IL, USA), and MedCalc 13 for windows (MedCalc Software bvba, Ostend, Belgium). Results The experimental group involved 15 males and 15 females with a median age of 23.5 years while the control group included 15 males and 15 females with a median age of 25 years. The demographic data of all patients who completed the study are illustrated in Table 1. There was no statistically significant difference between the two studied groups regarding the reduction of comedonal and non-comedonal lesions count as well as GAGS assessment at both bassline baseline and monthly follow-up visits except at the fourth visit as demonstrated in Table 1 and Figure 1. At the fourth follow-up visit the control group showed a more significant improvement in GAGS than the experimental group, however, the difference became insignificant by the fifth visit. (Table 1, Figure 1C) Furthermore, the frequency of treatment-related side effects was more reported in the control (76.7%) group than the experimental group (20%) as shown in Table 1. Furthermore, there was no statistically significant difference regarding the relapse rates between both groups (p>0.05). Finally, the levels of patients’ satisfaction did not show a statistically significant difference between the two studied groups. Discussion To the best of our knowledge, the present study is the first to evaluate the efficacy and safety of a combination of oral zinc and systemic low-dose isotretinoin therapy in acne vulgaris AV patients. We hypothesized that the role of combining zinc to isotretinoin in AV is not always to correct a
Concomitant Therapy of Oral Isotretinoin with Multiplex Pulsed Dye Laser and Nd: YAG Laser for Acne
J Clin Aesthet Dermatol. 2022;15(9):20–24. by Sheetal Sapra, MD, FRCPC; Shantel DJ Lultschik, BHSc; Jennifer VH Tran, BSc; and Kevin Dong All authors are with the Institute of Cosmetic and Laser Surgery in Oakville, Ontario. FUNDING: No funding was provided for this article. DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article. ABSTRACT: Objective. To evaluate concomitant therapy of oral isotretinoin with multiplex pulsed dye laser and Nd:YAG laser. Methods. A retrospective chart review of patients who received treatment of oral isotretinoin and non-ablative laser therapy to treat acne vulgaris at a single outpatient dermatology clinic site in Ontario, Canada between 2009 and 2017. Results. 187 patients were included, consisting of 45.5 percent males (n=85) and 54.5 percent females (n=102) with a mean age of 21.4 years. 31.6 percent (n=59) of patients reported experiencing side effects from concomitant isotretinoin and NAL therapy, the most common being eczema (n=14), erythema (n=11), significant dry skin/lips/eyes (n=8), flushing (n=6), and bruising (n=6). 99.2 percent of patients achieved clear or almost clear at treatment completion. Of those who expressed satisfaction, 65.2 percent (n=122) reported being satisfied with the treatment and the remaining patients did not report satisfaction nor dissatisfaction. Limitations. Limitations exist mainly due to the absence of standardized lesion counts and a comparator cohort. Thus, it is not possible to comment on whether the combination of isotretinoin and NAL is more efficacious that either treatment alone. Conclusion. Concomitant use of isotretinoin and non-ablative laser therapy is a safe and effective treatment option for acne vulgaris that provides patient satisfaction. Keywords: Acne vulgaris, isotretinoin, non-ablative laser, pulsed dye laser, nd:yag Acne vulgaris is a chronic inflammatory disease affecting the pilosebaceous follicles.1 Acne is associated with significant physical and psychological morbidity, such as anxiety, depression, poor self-esteem, and permanent scarring.1, 2 Due to acne’s adverse effect on quality of life, it is important to offer effective and safe treatment options to patients.2 Treatments for acne include topical and systemic medication, as well as therapies such as ablative and non-ablative laser treatments or chemical peels.1 This study will focus on the combination of oral isotretinoin and non-ablative laser (NAL), specifically multiplex pulsed dye laser (PDL) and Nd:YAG laser delivered through one unique device. Oral isotretinoin is considered the most efficacious treatment with the ability to affect all pathogenic factors of acne.1,3,4 Canadian, American, and European clinical practice guidelines suggest isotretinoin be used for moderate to severe acne, and only as a first-line treatment to treat severe nodulocystic and papulopustular acne.5-8 In a recent review study, complete improvement was observed in 93.9 percent of patients, with only mild side effects, such as cheilitis (90-100% of patients).9 NAL therapies have been shown to effectively and safely treat both active acne and acne scarring. Nd:YAG laser and PDL treat active acne by causing thermal coagulation of the sebaceous glands, leading to decreased sebum production.10 Combination therapies are often successful in treating acne; however, as per the American Academy of Dermatology (AAD) guidelines, there is hesitancy to combine oral isotretinoin with NAL therapies.1 Meanwhile, there are no Canadian-specific guidelines regarding oral isotretinoin and NAL therapy usage. Early case studies saw poor wound healing and keloid formation in patients who had concurrently or recently taken isotretinoin and received NAL or ablative laser therapy, leading to the AAD recommendation to delay cutaneous laser treatments until 6 to 12 months after discontinuing isotretinoin.1,11-13 In contrast, recent research has supported the safety of NAL treatment during isotretinoin use, where studies report no evidence of scarring, keloid formation, or abnormal wound healing and there was insufficient evidence to support delaying treatments such as NAL procedures.14-17 A slight majority of physicians surveyed would recommend patients wait at least six months or longer after isotretinoin use before undergoing NAL treatment; however, 76 percent of experts have never seen complications with NAL treatment while receiving isotretinoin or within six months.11,16 Currently, literature is not conclusive on the use of non-ablative laser therapies during and following the use of oral isotretinoin, leading to physician hesitancy to pursue this treatment modality. The primary objective of this study is to assess the safety of oral isotretinoin in combination with multiplex PDL and Nd:YAG laser in order to strengthen recommendations for its use as a treatment option for acne vulgaris. Secondary objectives include the assessment of effectiveness and patient satisfaction. Methods Data collection. A retrospective medical chart review of patients who received treatment of oral isotretinoin with multiplex PDL and Nd:YAG laser therapy to treat acne vulgaris was conducted. All patients received treatment at one outpatient dermatology clinic site. A research ethics board approved this study prior to all chart review activities. A waiver for consent was obtained due to the retrospective nature of the study, although patients included in the photo figures provided written consent to the use of these photos for research purposes. The electronic database was searched to find all patients who received both oral isotretinoin and NAL therapy from January 1st, 2009 to August 17th, 2017 for treatment of acne vulgaris. NAL therapy consisted of sequential emission of 585nm PDL and 1064nm Nd:YAG from one unique, multiplex delivery system (Cynergy™, Cynosure®; Westford, Massachusetts, United States). The following settings were used for the laser therapy: fluence 6-8J/cm2, spot size 10mm, and pulse duration 10-20ms depending on skin type. Patients were not incentivized to receive concomitant treatment and paid for multiplex PDL and Nd:YAG laser with isotretinoin therapy. Exclusion criteria included patients who did not return to the study site for follow-up after the initial prescription was provided, patients who received multiplex PDL and Nd:YAG laser therapy only prior to taking oral isotretinoin or started more than six months after taking oral isotretinoin, and patients who received oral isotretinoin with multiplex PDL and Nd:YAG laser therapy for any indication other than acne vulgaris. Demographic data of study participants is included in Table 1. Clinical evaluations for effectiveness, patient reported satisfaction, and safety and tolerability of oral isotretinoin with multiplex PDL and Nd:YAG laser therapy were completed from review
Risk of Skin Cancer with Phototherapy in Moderate-to-Severe Psoriasis: An Updated Systematic Review
J Clin Aesthet Dermatol. 2022;15(6):68-75. by Akshitha Thatiparthi, BS; Amylee Martin, BS; Jeffrey Liu, BS; and Jashin J. Wu, MD Ms. Thatiparthi is with Western University of Health Sciences in Pomona, California. Ms. Martin is with the School of Medicine at University of California in Riverside, California. Mr. Liu is with the Keck School of Medicine at the University of Southern California in Los Angeles, California. Dr. Wu is with the Dermatology Research and Education Foundation in Irvine, California. FUNDING: No funding was provided for this study. DISCLOSURES: The author reports no conflicts of interest relevant to the content of this article. ABSTRACT: Phototherapy is a standard treatment for moderate-to-severe psoriasis. However, concern remains regarding the associated cutaneous carcinogenic risk. Our objective is to conduct a systematic review of skin cancer risk for psoriasis patients treated with phototherapy. To achieve our goal, we searched Cochrane, PubMed, and Embase databases. We aimed to evaluate existing literature (from July 1, 2010, to December 31, 2020) on phototherapy for all Fitzpatrick skin phototypes (FSP) which includes 71 articles, and eight articles being categorized in this review. Five studies did not report an increased skin cancer risk with narrowband-ultraviolet blue (UVB) and unspecified UVB for FSP II through VI, with one study not reporting FSP. Three studies did report an increased risk of skin cancer with narrowband-UVB and broadband-UVB for FSP I-VI, with one study also not specifying skin phototypes or UVB phototherapy type. Additionally, a study with psoralen and ultraviolet A with and without narrowband-UVB demonstrated an increased risk of skin cancer in phototypes III and IV. The most commonly reported secondary outcomes with phototherapy were actinic keratosis (123) and solar lentigines (10). Numerous patients were also on additional therapies including methotrexate, acitretin, and biologics. Study limitations include publication bias due to limited number of studies published on this topic in the last ten years along with heterogeneity in reporting. The relationship between phototherapy, psoriasis, and cutaneous oncogenic risk remains contradictory. While phototherapy for psoriasis is an efficacious therapy, further studies are needed to understand the cutaneous oncogenic risk based on FSP to help clinicals tailor treatment recommendations based on skin phototypes. Keywords: Cancer, phototherapy, psoriasis, PUVA, UVB, melanoma, narrowband UVB, broadband UVB Since phototherapy was discovered to be an effective psoriasis treatment in the twentieth century, it has been a mainstay therapeutic option for moderate-to-severe psoriasis. 1,2 Skin conditions commonly treated with phototherapy include psoriasis, atopic dermatitis, vitiligo, mycosis fungoides, and morphea.3 The broad therapeutic options for phototherapy can be attributed to its mechanism of action. As ultraviolet light enters the dermis and epidermis, DNA damage and photoproducts are produced. The byproducts and resulting damage induce apoptosis in keratinocytes, fibroblasts, inflammatory cells, and endothelial cells allowing suppression of the inflammatory cascade.3 Further, the local immunosuppression inhibits DNA cell turnover and induces apoptosis of T lymphocytes. As psoriasis results from dysregulation of T cells and dendritic cells causing an inflammatory cascade leading to keratinocyte hyperproliferation, phototherapy is able to induce remission and improve clinical outcomes.4 Two main types of phototherapy are used in the treatment of psoriasis, ultraviolet A (UVA) and ultraviolet B (UVB). Ultraviolet A phototherapy emits wavelength between 320 and 400 nanometers (nm).3,5 Psoralen is an organic compound, which can be derived from plants or synthetically created. When psoralen is combined with UVA, they generate a greater phototoxic effect. This combination of UVA and psoralen is known as PUVA.3,6 PUVA is able to penetrate deep into the dermis.3 However, utilization of PUVA has declined over the years due to a dose-dependent risk of carcinogenesis and additional adverse effects.7-12 Initial treatments for psoriasis involving UVB included combining the treatment with tar and anthralin paste or oral/topical psoralen in conjunction with UVA irradiation.2 Broadband UVB (BB-UVB), which emits wavelengths between 290 to 320 nm, became an increasingly popular option.2,3 In the 1980s, researchers discovered wavelengths of 311 to 313 nm had superior efficacy compared to BB-UVB.2 Narrowband UVB (NB-UVB) was able to induce greater clinical and histopathological clearance with greater remission rate compared to BB-UVB.13-15 Due to superiority of NB-UVB, the phototherapy type became a standard of care.5 The prescribed dosage of UVB administered depends on either Fitzpatrick skin phototype (FSP) or minimal erythema dose (MED) testing16-18 Fitzpatrick skin phototype is more commonly utilized to determine initial dose and subsequent increase than MED.18 Fitzpatrick skin phototype is a skin classification system used to rank skin phototypes (from I to VI) based on human skin pigmentation and reaction to UV light.16, 19 This ranking system is relevant to our review as a relationship has been established in literature reporting higher FSP are able to better tolerate higher doses of ultraviolet radiation (UVR) compared to lower skin phototypes. Further, erythema resulting from UVR has been correlated with increased cancer risk due to greater DNA damage in lower FSP compared to higher skin phototypes.17, 18, 20-22 As UV light has phototoxic and cariogenic properties, the carcinogenic risk of this treatment modality in psoriasis needs to be evaluated. Recent comprehensive reviews were published in 2010 and 2015 summarizing literature up to 2015 on skin cancer risk with phototherapy.5, 23 However, both studies broadly examined carcinogenic risk of phototherapy in psoriasis patients on Caucasians vs non-Caucasians. Our review’s objective is to conduct a comprehensive review of multiple databases with further examination of cutaneous carcinogenic risk by FSP. Additionally, we hope to categorize recent additional research published on this topic. Overall, we aim to systematically categorize literature on skin cancer risk with PUVA, UVB, NBUVB, and BBUVB, based on skin phototypes, where available. We hope our comprehensive review will help guide physicians in selecting an appropriate therapeutic regime for patients with psoriasis based on specific skin phototypes. Methods Our systematic review was conducted according to the Preferred Reporting items for Systematic Reviews and Meta-Analyses. Pubmed, Embase and Cochrane databases were queried on December 21, 2020 using the following search terms: “Psoriasis” AND “UVB therapy” AND “skin” AND “cancer” OR “neoplasm” OR “melanoma”. We also utilized the following search
Enhancing Topical Pharmacotherapy for Acne and Rosacea: Vehicle Choices and Outcomes
J Clin Aesthet Dermatol. 2022;15(5):36–40. by Lawrence J. Green, MD; Edward Lain, MD; Thomas Prunty, MBA; and Robert Rhoades, PhD Dr. Green is with George Washington University School of Medicine in Washington, D.C. Dr. Lain is with Sanova Dermatology in Austin, Texas. Mr. Prunty and Dr. Rhoades are with AraMed Strategies, LLC, in Middletown, Delaware, and Steamboat Springs, Colorado, respectively. FUNDING: Mr. Prunty and Dr. Rhoades from AraMed Strategies, LLC, received financial support from Sol-Gel Technologies, Ltd of Ness Ziona, Israel, for medical writing. DISCLOSURES: Dr. Green is an investigator for Sol-Gel Technologies, Ltd. The other authors report no conflicts of interest relevant to the content of this article. ABSTRACT: The choice of vehicle is an important consideration in the treatment of acne and rosacea. Agents used to treat these common conditions may be limited by multiple factors, including poor stability during storage, limited residence time in the skin and follicular unit, and high potential for skin irritation. Novel drug delivery systems have been developed to address these problems, including microencapsulation, liposomal encapsulation, and the use of a variety of nanocarriers. New vehicle technologies for acne and rosacea treatments have appeared over the past 20 years and have somewhat improved stability, tolerability, and possibly efficacy. One of the latest vehicle technologies in acne and rosacea to enhance efficacy, stability, and tolerability is microencapsulation of benzoyl peroxide and tretinoin, which resulted in significant efficacy and good tolerability in patients with each of these two diseases. Other new vehicle technologies include a polymeric form of tretinoin and a microsphere product that combines tretinoin plus clindamycin. It is likely that there will be more reports of clinical success as experience with the rapidly evolving delivery technologies increases. This review summarizes drug delivery systems that have been developed with the aim of improving outcomes for patients being treated for either acne or rosacea. It also focuses, where possible, on formulations that have been evaluated in clinical studies. Keywords: Acne, rosacea, microencapsulation, vehicle, topicals Topical agents for acne and rosacea are used as both first-line and adjunctive therapy with oral medications.1-3 This approach to treatment has important advantages, including the ability to achieve high concentrations of medication to the target tissue and decreasing or eliminating systemic exposure that may lead to adverse events (AEs).4 Although topical therapy should avoid AEs associated with systemic medication administration, the efficacy, safety, and tolerability of topical therapy is influenced by percutaneous penetration, retention at the target for a sufficient time to obtain the desired therapeutic effect, and avoidance of adverse local reactions that may affect adherence.5,6 It has been noted that the drug product is only one of multiple components that determine the efficacy and tolerability of topically applied therapies such that the performance of a topical medication is also influenced by characteristics of the vehicle formulation that may influence penetration, permeation, irritancy, and patient preference.7 The effects of the active drug ingredient in a topical medication are influenced by the vehicle base employed for delivery (e.g., ointment, cream, lotion, gel, foam, spray), and it has been repeatedly shown that vehicle selection can influence both adherence to therapy and treatment outcomes.8-11 Drug performance is also significantly impacted by the delivery system in which it is packaged (e.g., microcapsules, liposomes, transferomes, water-in-oil-in-water emulsions, chitosan nanoparticles, solid lipid nanoparticles, cellulose acetate nanofibers, polyvinyl alcohol conjugates, silicone capsules, etc.) prior to mixing with the vehicle.12, 13 Drug delivery systems have been shown to influence efficacy, tolerability, and adherence for topical therapies.14-16 Many different delivery technologies have been applied to topical treatments, but only a few have translated into commercial products for dermatologic diseases. This may be due to the inability to economically scale the technology and failure to achieve desired controlled release.12,17 This review summarizes drug delivery systems that have been developed with the aim of improving outcomes for patients being treated for either acne or rosacea. It also focuses, where possible, on formulations that have been evaluated in clinical studies. Microencapsulation In general, encapsulation creates a barrier between the medication and the skin. The slow migration of medication from the microcapsules also provides sustained delivery. Microencapsulation techniques typically result in microspheres with a fine coating of inert, natural, or synthetic polymeric materials deposited around solid or liquid micronized drug particles.18 When microspheres are applied to the skin, the amount of free drug in the preparation penetrates the epidermis. Catabolized drug is replaced by continued release of the product from the microspheres.19 The controlled release of drug from microcapsules has the potential to extend the time over which it is delivered to the skin after a single application and to decrease the risk for very high concentration of the drug to produce local adverse reactions.20-22 Microencapsulation can be achieved with a sol-gel process in which drug molecules are entrapped in the inner porosity of a silica-based matrix.18 In this process, amorphous silica is made by forming interconnections among colloidal particles (the “sol”) under increasing viscosity until a rigid network, the silica shell (the “gel”), is formed with pores of submicron dimensions. Drug encapsulation is achieved by a technique known as interfacial polymerization. The process results in a drug core surrounded by a silica capsule shell.23 This technology has been employed in an effort to enhance the efficacy, tolerability, and compatibility of two drugs that have been used extensively in the treatment of acne: benzoyl peroxide (BPO) and tretinoin. In the combination treatment for acne, encapsulated tretinoin is protected from oxidative decomposition by BPO, which enhances the stability and shelf life of tretinoin. The silica shells also create barriers between both tretinoin and BPO and the skin, which have the potential to decrease the irritation that often follows topical application of BPO or tretinoin. For BPO, skin lipids control the rate of release from the silica capsule since the release mechanism involves migration of the skin’s natural secretions through the silica pores into the capsule. The skin lipids dissolve the BPO crystals, carrying it to the skin surface. The controlled release of
Approaches to Field Therapy for Actinic Keratoses: Relating Clinical Trial Results to Real-world Practice—A Commentary
J Clin Aesthet Dermatol. 2022;15(4)40–43. by David M. Pariser, MD Dr. Pariser is with the Department of Dermatology at Eastern Virginia Medical School and Virginia Clinical Research, Inc. in Norfolk, Virginia. FUNDING: Funding was provided by an unrestricted grant from Biofrontera. DISCLOSURES: The author reports no conflicts of interest relevant to the content of this article. ABSTRACT: There have been multiple direct and indirect comparison studies evaluating different field therapies used in the treatment of actinic keratosis (AK). A recent clinical trial directly compared 5% fluorouracil (5-FU), imiquimod, ingenol mebutate, and methyl aminolevulinate photodynamic therapy (MAL-PDT), reporting that 5-FU was superior to the other treatments in achieving sustained clearance of 75 percent or greater of AK lesions compared to baseline. In this commentary, the author reviews and discusses the methods and results of this comparison study and propose these results are limited by a number of factors, such as the selected primary % clearance endpoint, grade range of included AKs, and treatments included in the comparison, when considered in the context of other clinical and real-world comparison studies evaluating AK field therapies. The author postulates that patient acceptance of and adherence to field therapy regimens for the treatment of AK may be better evaluated in a real-world setting. Additionally, the author suggests that selection of field therapy in the treatment of AK should be driven by consideration of relevant patient-, disease-, and treatment-related factors, and what is considered best may differ from patient to patient, depending on each patient’s individual needs and expectations. Keywords: Compliance, 5-fluorouracil, photodynamic therapy, diclofenac, ingenol mebutate, imiquimod, cancerization Actinic keratosis (AKs) is one of the most prevalent diagnoses in dermatology and is expected to rise in frequency with the aging population and increased exposure to sunlight.1 In 2015, over 35 million cases of AK were treated in the Medicare Part B fee-for-service population, highlighting the treatment burden of this condition.2 Current researchers regard AK lesions as early squamous cell carcinoma and, as such, should be treated.3 Field-directed therapy is desirable for treating AKs due to the high recurrence rate for cutaneous squamous cell carcinoma (cSCC) when therapy is only lesion-directed.4 Commonly used approaches of field therapy for AKs include 5-fluorouracil (5-FU), topical nonsteroidal anti-inflammatory drugs e.g., (diclofenac sodium, piroxicam), chemical peeling, immunomodulators e.g., (imiquimod and ingenol mebutate), and photodynamic therapy (PDT).3,5 A newly approved field treatment, tirbanibulin ointment, has also been shown to be safe and effective.6 Ingenol mebutate’s European Union (EU) marketing authorization was withdrawn due to increased skin cancer risk. Final results from a study comparing ingenol mebutate with imiquimod indicated a higher occurrence of skin cancer with the former agent.7 Different options for field therapy have been compared in multiple meta-analyses which have provided variable results. One network meta-analysis which included results from 25 trials and 5,562 patients, indicated that aminolevulinic acid (ALA-PDT) delivered as a gel (BF-200) had the highest efficacy for complete clearance followed by imiquimod and 5-FU.8 This European meta-analysis excluded trials evaluating the 20% ALA stick because it has not been approved in Europe. However, the author includes this treatment in a sensitivity analysis to assess its relative efficacy, and according to this analysis, the BF-200 ALA PDT remained the treatment with the highest ranking, followed by imiquimod, ALA stick PDT, and 5-FU. A second meta-analysis that included results from 32 studies and 6,473 patients and employed complete clearance as an endpoint resulted in the following ranking: 5-FU > ALA-PDT > imiquimod > ingenol mebutate = methyl aminolevulinate (MAL)-PDT.9 A recent retrospective real-world chart compared 5-FU, ingenol mebutate, imiquimod, cryosurgery alone, and cryosurgery in combination with one of the topical modalities (PDT was not included in this study). Cryosurgery in combination with a topical modality provided slightly better results than any individual modality in the mean reduction of AKs.10 Current guidelines provide no clear recommendations about which approach should be used11,12 and the choice of treatment often depends on the preferences of patients and their treating physicians. While meta-analyses provide potentially useful information, they are not generally viewed as a substitute for direct comparison of treatment alternatives in controlled clinical trials.13 A recent study was carried out to fill this gap by directly comparing four approaches to field therapy: 5-FU cream, imiquimod cream, MAL-PDT, and ingenol mebutate gel.14 While addressing an important clinical issue, this trial also raised several questions that demand consideration. This brief review addresses the results of this study in the larger context of clinical and real-world studies concerning with field therapy for AKs. Direct comparison of field therapies The 12-month, randomized controlled trial carried out by Jansen et al14 compared treatment success of 5% 5-FU cream, 5% imiquimod cream, MAL-PDT, and 0.015% ingenol mebutate gel in patients with AK lesions of any grade. The primary outcome of this trial was the proportion of patients who remained free from treatment failure (defined as a reduction of greater than or equal to 75% in the number of AK lesions counted at baseline occurring at 3 months after the last treatment [initial failure] or at 12 months after initially successful treatment). A total of 624 patients were included in the trial. At 12 months, the cumulative probability of remaining free from treatment failure was significantly higher among patients who received 5-FU (74.7%) than among those who received imiquimod (53.9%), MAL-PDT (37.7%), or ingenol mebutate (28.9%) ( less than or equal to 0.001 for all comparisons). There are several aspects of the design and results from this study that deserve comment. First, the primary endpoint (achievement of greater than or equal to 75% clearance of lesions) was somewhat unusual. Most recent controlled trials that have evaluated field therapies for AKs have used complete clearance as a primary endpoint,15-20 and this was also the endpoint employed in the two network meta-analyses described above.8,9 Results for complete clearance were not reported by Jansen et al.14 Second, results from the study of Jansen et al appear to differ from those obtained for the same agents evaluated in other clinical trials.
Spotlight Interview: Douglas DiRuggiero, DMSc, MHS, PA-C
J Clin Aesthetic Dermatol 2022;15(3 Suppl 1):S11–S13 Douglas DiRuggiero, DMSc, MHS, PA-C, is a certified physician assistant at the Skin Cancer & Cosmetic Dermatology Centers in Rome and Cartersville, Georgia. Douglas graduated with honors from Duke University Physician Assistant Program in Durham, North Carolina, where he also earned his Master of Health Sciences degree. He completed a doctorate degree in 2019 from the University of Lynchburg in Lynchburg, Virginia. Douglas practiced internal medicine for several years but has specialized in dermatology since 2000. Focused on the diagnosis and treatment of all skin, hair and nail diseases, he also enjoys the surgical aspects of dermatology. Douglas has been published in dermatology journals and lectures frequently at medical conferences throughout the United States. He is the Founding President of the Georgia Dermatology Physician Assistant Society and is the Immediate Past President of the New York Dermatology PA Society. What inspired you to pursue a career in dermatology? Douglas: I was fortunate in my youth to have never needed the consultation of a dermatologist, so I never had exposure to the specialty until I started clinical rotations in PA school. It was there that I watched ER, pediatric, and family medicine clinicians wrestle with cutaneous presentations. It didn’t take long for me to realize two things: I was going to see a lot of patients with skin problems once I got into practice; and, more importantly, the 4 to 5 hours of didactic lectures during my first year of PA school would not sustain me. My first few years of practice were spent in a busy internal medicine clinic, and I was stuck in the rut of calling everything “maculopapular” and giving everyone lotrisone cream. Frustrated, I decided to pursue dermatology full time in order to learn and truly help others with these problems, so I made the transition, and I have loved every day of it! My inspiration came from a determination to get better at taking care of skin. What clinical areas in dermatology interest you the most? Douglas: I am focused on medical dermatology, but I have been working for a great Mohs surgeon for the past 16 to 17 years and enjoy doing complex closures a few days each month. I am a strong advocate and utilizer of biologic medications, and I treat hundreds of patients with immune-mediated skin disorders (psoriasis, atopic derm, hidradenitis suppurativa). Biologic medications give me an opportunity to be a hero every day, as patients routinely reach levels of clearance never before experienced. I see all age groups with all skin, hair, and nail problems. In short, I enjoy complex medical dermatology but love having surgeries sprinkled throughout my schedule. What emerging treatments are you most excited about? Douglas: What a fun time to be a dermatology prescriber! When I started years ago, we had prednisone, methotrexate, topicals, and phototherapy for psoriasis, and all of them had more cons than pros. Now, with the development of biologics, the face of dermatology has completely changed. Stay strapped into your seat because the renaissance of atopic dermatitis therapeutics is unfolding and it’s going to be good! How do you keep patients engaged in and adherent to their treatment plans? Douglas: Patients are more likely to remain engaged in the diagnostic process (and subsequent treatments) when they know you, as the clinician, are engaged and committed to making them better. When patients come to our clinic, I let them know they are “gaining a new family…and family sticks together and helps each other.” On follow-up appointments, I will often say, “I’m going to ask you about your skin in just a minute, but first tell me about how you are doing?” Like grandma used to say, “People don’t care what you know until they know that you care.” Creating simple and understandable ways to describe diseases and therapeutics to patients is also important, but we shouldn’t be afraid to admit when we just don’t know something. My patients are willing to accept a gap in knowledge because they know I’m going to do the biopsy, order the test, do some research, or get help from others. However, despite a great patient-provider relationship, many patients still do not adhere to agreed-upon treatment plans. If you have confirmed the diagnosis and developed a good treatment plan, but aren’t seeing improvements in a patient, always consider the possibility of nonadherence. Keeping patients engaged in their treatment plans means addressing issues that make adherence a challenge. Offer solutions. Seek treatment alternatives. Lastly, as clinicians, being positive and offering hope to our patients is a critical part of the holistic treatment process. As a provider, what gives you the greatest sense of satisfaction in what you do? Douglas: I’ve got the best job in the world. I get to meet with dozens of people each work day and talk with them about their jobs, their families, their hobbies, their concerns, and…oh yeah, their skin problems! My first several years as a derm practitioner were highly focused on confirming the right diagnosis and not missing anything bad, and don’t get me wrong…that is still the primary goal—after all, accurate diagnoses lead to successful treatments, less suffering, and improved quality of life for my patients—but now, my 22 years of experience means the diagnosis comes more quickly through pattern recognition and repetition, leaving more time to engage and minister to the whole person, not just the person’s skin complaint. My greatest sense of achievement isn’t found in the number of patients I see, but rather in the hug I receive from the patient whose psoriasis or atopic dermatitis has disappeared or whose surgical scar has become barely noticeable, or in the immense look of relief on a patient’s face after telling them their groin rash is fungal, not an STD. Simply put, I feel immense satisfaction when I can offer help, hope, and healing to people. What charitable organizations and professional societies are you involved in? Douglas: Contributing to and supporting the educational and
Effective Intense Pulsed Light Protocol in the Treatment of Moderate to Severe Acne Vulgaris of the Chest and Back
J Clin Aesthet Dermatol. 2022;15(3):22–25. by Domenico Piccolo, MD; Dimitra Kostaki, MD; Caterina Dianzani, MD, PhD; Giuliana Crisman, MD; and Claudio Conforti, MD Drs. Piccolo, Kostaki, and Crisman are with the Skin Centers in Avezzano-Pescara, Italy. Dr. Conforti is with the Dermatology Clinic of Hospital Maggiore at the University of Trieste in Trieste, Italy. Dr. Dianzani is with the Plastic and Reconstructive Surgery Department at Campus Biomedico University in Rome, Italy. FUNDING: No funding was provided for this article DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article. ABSTRACT: Background. Acne is defined as a chronic inflammatory disease of the pilosebaceous units, mainly affecting the face of young adults, but the chest and back can be involved as well. Oral antibiotics, topical retinoids, azelaic acid, benzoyl peroxide, and isotretinoin represent the most common treatment used for the treatment of acne, but several adverse effects and a lack of durable remission, with poor adherence by the patients, have been reported thus far. Lasers have been shown to be effective and safe to treat acne; intense pulsed light (IPL) demonstrates high efficacy rates, minimal discomfort, rapid recovery times, and excellent cosmetic and therapeutic outcomes. Objective. In this prospective study, we assessed the efficacy, safety, and reproducibility of a novel IPL protocol as a monotherapy in the treatment of acne of the chest and back. Methods. We included patients (N=50) aged 14 to 30 who presented with moderate papulopustular acne sited on the chest and back (Cook’s Acne Grading Scale method 4–6, Pillsbury Scale III–IV). We performed four IPL sessions at two-week intervals on each patient. Results: An excellent outcome was achieved in 50 percent of the patients and a good outcome in the 35 percent of the patients. Patients experienced light erythema and mild burning as the most common side effects, which spontaneously resolved within 24 to 96 hours. Conclusion. Consistent with previous reports, our study demonstrated IPL to be a safe and effective treatment for severe cases of acne on the chest and back, providing excellent aesthetic and therapeutic results in 85 percent of treated patients. Keywords: Papulopustular acne vulgaris, acne, chest, back, intense pulsed light, IPL Acne vulgaris (AV) is an inflammatory disorder of the sebaceous glands of some areas (e.g., face, trunk, buttocks) that onsets most frequently during adolescence and is clinically characterized by comedones (comedonal acne), papulopustules (papulopustular acne) or nodules and cysts (nodulocystic acne or acne conglobata).1 All forms can result in punctiform, depressed or hypertrophic scars, with considerable psycho-emotional stress on the patient. Acne affects up to 85 percent of young people, with an average age between 14 and 19 years in males and between 10 and 17 years in females.2, 3 Although AV has long been considered a disease of puberty, it has been increasingly observed in pre- and post-adolescents as well.4 A lower incidence in individuals of Asian and African descent has been described.5 The etiopathogenesis of acne is multifactorial and it involves the role of androgens, keratinization, the infection of Cutibacterium acnes, and family history.5 Even if AV is not a devastating or life-threatening condition, it is significantly associated with social impairment, diminished quality of life, depression, anxiety, anger, and poor self-esteem.6 Given the negative psychological impact of AV, early initiation of effective therapy is recommended, especially in the inflammatory variety of AV. The aim of AV treatment is to reduce and control the progression of acne lesions, reduce the risk of acne development and reduce the duration of the disease.7 The choice of therapy depends on several factors, such as the age of patients, site, type and severity of acne, side effects, costs, and treatment availability. Combined treatments also can lead to excellent results in complex cases. The most frequent combination therapies are based on the combination of oral antibiotic therapy, chemical peels, and the recourse to camouflage with variable grades of resolution and/or satisfaction. Oral antibiotics, topical retinoids, azelaic acid, benzoyl peroxide, and isotretinoin represent the most common treatments used to treat patients with acne, though adverse effects and a lack of durable remission, with a subsequent poor treatment adherence, have been reported.8–11 Some therapies for AV can cause skin inflammation, burning, or itching, leading to treatment interruption by patients.12 Lasers have been demonstrated to be a viable alternative for these acne treatments. The 1064-nm Nd:YAG laser and intense pulsed light (IPL) have been investigated in the past few years and both therapies demonstrate excellent cosmetic and therapeutic outcomes. Based on the variability in frequency and power usage of these technologies, IPL is a useful laser in the treatment of acne, since its flexibility can achieve notable improvements within the context of the variable inflammatory and non-inflammatory clinical presentation of acne.13–15 In this prospective study, we assessed the efficacy, safety, and reproducibility of a novel IPL protocol as a monotherapy in the treatment of acne of the chest and back. Methods Fifty patients ranging from 18 to 40 years of age (mean age 23.8 years old) with Fitzpatrick Skin Types II to III and moderate papulopustular acne on chest and back were retrospectively enrolled from our private practice centers. Written informed consent for participation in this study was obtained from all patients prior to enrollment. Patients were enrolled according to the Cook’s Acne Grading Scale method (inclusion criterion: Cook’s grading 4–6) and according to the Pillsbury Scale (inclusion criterion: Pillsbury Scale III–IV). Thirty-two of 50 patients (64%) presented with a history of conventional topical and systemic acne treatments with antibiotics and isotretinoin without achieving a remarkable improvement. Each patient signed an informed consent before starting treatment. Exclusion criteria included a history of systemic retinoid use within six months prior to treatment, history of antibiotics within one month of treatment and use of topical antiacne treatment within three weeks prior to enrollment, along with a history of photodermatosis or photosensitizing reactions or any ongoing condition that could interfere with the evaluations. Pregnant and/or breastfeeding patients were also excluded. During the study, patients did not undergo any
Treatment of Melasma with Intralesional Tranexamic Acid Versus Cryotherapy
J Clin Aesthet Dermatol. 2022;15(2):44–48. by Khaled Gharib, MD and Hala M. Morsi, MD All authors are with the Dermatology Department, Faculty of Medicine at Zagazig University in Zagzig, Egypt. FUNDING: No funding was provided for this article. DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article. ABSTRACT: Background. Melasma is a relatively common, acquired facial skin disorder of hyperpigmentation. Though it occurs in both sexes, nearly 90% of patients are female. It manifests as hyperpigmented macules and patches distributed symmetrically on the face, neck, and, rarely, the upper limbs. Objective. The aim of this study was to evaluate and compare the clinical efficacy and adverse effects of intralesional injection of tranexamic acid (TA) versus cryotherapy in the treatment of melasma. Methods. Patients were divded into two groups: Group A and Goup B. Group A comprised 28 patients aged 27 to 50 years. They received localized intralesional injections of TA. According to Wood’s light examination, patients were divided into two subtypes; 13 patients with mainly dermal-type melasma and 15 patients with mainly mixed-type melasma. Family history was obtained in 12 patients. Group B comprised 28 patients aged 29 to 46 years were included. They were treated with cryotherapy. According to Wood’s light examination, the patients were divided into two subtypes of melasma; 8 patients with mainly dermal-type melasma and 10 patients with mainly mixed-type melasma. Results. There were no statistically significant differences between Group A and Group B according to contraception, sun exposure, and family history. There was a statistically significant difference between Group A and Group B according to previous treatment. There was no statistically significant difference between the two groups according to drug allergy. There were no statistically significant differences according to systemic disease or general examination. Conclusion. Intralesional tranexamic acid is a safe and effective method for the treatment of melasma with no risk of PIH, thrombosis, or bleeding; however, more sessions with longer follow-up periods are recommended, as the final response may take several months to occur. Cryotherapy was neither safe nor effective due to the risk of PIH. Keywords: Melasma, hyperpigmentation, tranexamic acid, cryotherapy Melasma is a relatively common, acquired facial skin disorder of hyperpigmentation. Though it occurs in both sexes, nearly 90% of the patients are female.1 It manifests as hyperpigmented macules and patches distributed symmetrically on the face, neck, and, in rare instances, the upper limbs.2 The role of tranexamic acid (TA) in the treatment of melasma was first shown in 1979. Sadako3 tried to use TA to treat a patient with chronic urticaria. Incidentally, he found that the melasma severity of that patient was significantly reduced after 2 to 3 weeks. The mechanism of cryotherapy in the treatment of melasma is that discolored skin cells become damaged when they thaw after freezing. Liquid nitrogen is applied to the affected skin, and then heat transfers from the skin to the nitrogen, causing it to boil and evaporate. Once skin cells have been frozen with liquid nitrogen, they begin to thaw very slowly, causing water and ice to cross through the cell membranes and damage the cells. The cells then die causing inflammation. This process removes the discolored cells, allowing new cells to grow in their place.4 The aim of this study was to evaluate and compare the clinical efficacy and adverse effects of intralesional injection of tranexamic acid versus cryotherapy in the treatment of melasma. Methods This study was carried out at the outpatient clinics of the Dermatology, Venereology, and Andrology Department, Faculty of Medicine, Zagazig University Hospitals from October 2018 until October 2019. Fifty-six patients with melasma aged 27 to 50 years were enrolled in the study. The study was approved by the Institutional Review Board (IRB) at Zagazig University. An informed consent was taken from each patient. Inclusion criteria Age above 18 years Moderate-to-severe melasma with a malar distribution Patient with mixed- or dermal-type melasma Exclusion criteria Pregnant or nursing women Women taking contraceptive pills at the time of the study or in the prior 12 months Any known bleeding disorders or the concomitant use of anticoagulants Women on any concurrent therapy for melasma Patients who were using any topical therapy for melasma, including hydroquinone, up to one month prior to enrollment Participants. Participants were randomly divided into two groups. Group A included 28 patients aged 27 to 50 years. They received localized intralesional injections of TA. According to Wood’s light examination, patients were divided into two subtypes; 13 patients with mainly dermal-type melasma and 15 patients with mainly mixed-type melasma. Family history was obtained from 12 patients. Group B included twenty-eight patients aged 29 to 46 years. They were treated by cryotherapy. According to Wood’s light examination, the patients were divided into two subtypes of melasma; eight patients with mainly dermal-type melasma and 10 patients with mainly mixed-type melasma. A family history was obtained from 18 patients. Patient satisfaction. A questionnaire was given to patients at the end of treatment to assess their degree of improvement. The patient’s self-assessment was graded along four scales of pigmentation lightening: more than 75% lightening (excellent); 51 to 75% (good); 26 to 50% (fair); and 0 to 25% (poor). Side effects. Any side effects observed, such as pain, post procedure erythema, or edema, were recorded at each session. For the cryotherapy group, hyperpigmentation was also recorded. Results Group A (intralesional injection of tranexamic acid). This group included 28 female patients, and their ages ranged from 27 to 50 years with a mean of 37.71 ± 5.15. Eight patients had skin phototype III (28.6%), and 20 patients had phototype IV (71.4%). The duration of melasma ranged from 1 to 16 years with a mean of 4.5 ± 3.8. According to Wood’s light examination, 13 patients (46.4%) had dermal-type melasma and 15 patients (53.6%) had mixed-type melasma. Family history was obtained from 16 patients (57.1%). Group B (cryotherapy). This group included 28 female patients aged 29 to 46 years with a mean age of 39.36 ± 7.62. Twenty-four patients had skin
Spotlight Interview: Leigh Ann Pansch, MSN, FNP-BC, DCNP
J Clin Aesthetic Dermatol 2021;14(9 Suppl 1):S13–S17 Leigh Ann Pansch, MSN, FNP-BC, DCNP is a Certified Dermatology Nurse Practitioner practicing in Cincinnati, Ohio. Ms. Pansch received her Bachelor of Science in Nursing at Thomas More University in Kentucky. She has worked in women’s health, pediatrics, and nursing education for the University of Cincinnati and Cincinnati Children’s Hospital Medical Center where she was the first nurse to hold joint faculty appointment. She completed her Master’s of Science in Nursing with a family medicine focus at the University of Cincinnati College of Nursing and Health. She is a national speaker on such topics as pediatric dermatology, melanoma, and psoriasis, and she enjoys educating hundreds of high school students each year on sun safety. Ms. Pansch has served as a DCNP in pediatric, private practice, and hospital settings, and enjoys getting to know her patients and being attentive to their needs. She thrives on providing patient-centric care to her clients to achieve optimal treatment outcomes. She is married with three daughters. How did you begin your career as a nurse practitioner (NP)? Leigh Ann: I began my career in what I call “Mamas and Babies.” I spent about 15 years working in neonatal intensive care, special care nurseries, and labor, delivery, and postpartum care. I’ll never forget how overwhelmed I felt at first learning how to be a nurse in a specialized area of practice. I asked so many questions! But I learned very quickly to align myself with other providers who pursued excellence. And then, eventually, I became one of the people that others went to for answers to their questions. This ignited a passion in me for education, and I began teaching clinicals for a local university. I honestly see the field of nursing as a continuum. To be successful caregivers, we must constantly strive to provide optimal care. Though I couldn’t have imagined this point when I began, my continuous pursuit of providing the best possible care to my patients led me from staff nurse to educator to nurse practitioner. What prompted you to specialize in dermatology? Leigh Ann: When I’m asked this question, I always say, “Dermatology chose me!” I learned early on in my career that I prefer chronic care. The opportunity to have long-term relationships with my patients has always suited me. During my last quarter of graduate school, several of my peers and I were meeting weekly for boards preparation. As the weeks went on, more and more of my peers received lucrative job offers. I recall one Thursday afternoon, I went home and had a bit of a pity party alone in my room fearing I’d never find a job as an NP. I decided to put all my energy into the things I did have control over: being the wife and mom I wanted to be, teaching well, and finishing school. My father died two weeks after I earned my Master’s of Science in Nursing. I networked with everyone I knew, I went on several interviews, received several offers, and took the best option, all while grieving the loss of my dad, but I like to think my father helped me during this time. The field of dermatology is so vast—it’s like the foreign language of medicine—but it pulls together all the different parts and the most interesting patients. And dermatological conditions involve numerous intricacies and intertwinings. The human body is so cool! What does being highly efficient and productive mean to you as a healthcare provider? Leigh Ann: I believe, as healthcare professionals, we often get lost in the loud squeaky wheels (like office drama/gossip, protocols, algorithms, and productivity) rather than focus on the questions our patients took time to write down, body maps they created “to help,” and small talk. In the United States, healthcare delivery has long focused on what we as providers “do” to patients. What I’m talking about now is a complete about-face, a full reversal, a shift in focusing not on what we do TO our patients but what we accomplish FOR our patients. We are headed to a billing system where quality of care and quality measures will be keys to reimbursement. Being highly efficient and highly productive does not simply mean our visits run on time as scheduled. It also doesn’t just mean we emptied our inboxes, answered all our messages, and signed all our charts. To put it simply, I believe being both highly efficient and highly productive means we focus our entire attention on the patient in the room—each patient, each time, every day. We are wise to turn off all the other noise and give each patient the attention they so deserve and expect. I tell my patients, “You may have to wait, but when I come in the room, you’re the only patient I’m seeing. You have my entire attention.” We can’t focus on our inbox, our smart watch, our time schedule, or our dinner plans. Rather, to truly pursue excellence in who we are and what we do, we have to pause, focus, and choose to prioritize each moment with our patients over everything else. This prioritization is, after all, what we’ve been trained to do. I call this the “Human Side” of being an NP or PA—It is the nuts and bolts of what goes on behind the closed doors of the patient exam room. If you’re looking for that “something” to improve your job satisfaction, patient quality measures, and career growth—all while overflowing in the support you can provide your entire team—read closely: Take your time. SLOW DOWN! Answer all your patients’ questions. Invest in their lives and know who they are. Walk in their shoes and try to understand their perspectives, needs, fears, and how “medicine” has failed them. Listen. Listen. Listen closely. Ask questions to understand what their goals are. Be persistent with realistic expectations, and help them reach their goals. We’ve all experienced those equally defeated moments in our careers where we failed. We
Evaluating Oral Glutathione Plus Ascorbic Acid, Alpha-lipoic Acid, and Zinc Aspartate as a Skin-lightening Agent: An Indonesian Multicenter, Randomized, Controlled Trial
J Clin Aesthet Dermatol. 2021;14(7):E53–E58. by Irma Bernadette S. Sitohang, MD, PhD; Anis Irawan Anwar, MD, PhD, Prof; Nelva K. Jusuf, MD, Phd, Prof; Abraham Arimuko, MD; Lilik Norawati, MD; and Silvia Veronica, MD Dr. Sitohang is with the Division of Cosmetic Dermatology, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital in Jakarta, Indonesia. Dr. Anwar is with the Department of Dermatology and Venereology, Faculty of Medicine Universitas Hasanuddin, Dr. Wahidin Sudirohusodo Hospital in Makassar, Indonesia. Dr. Jusuf is with the Division of Cosmetic Dermatology, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Sumatera Utara-Universitas Sumatera Utara Hospital in Medan, Indonesia. Drs. Arimuko, Norawati, and Veronica are with the Department of Dermatology and Venereology, Presidential-Army Central Hospital Gatot Soebroto in Jakarta, Indonesia. FUNDING: This study was funded by Mazta Farma. DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article. ABSTRACT: ClinicalTrials.gov identifier: NCT04105504. Background. For Asians, especially women with darker skin tones (Fitzpatrick Skin Types IV and V), clear, bright skin is considered highly desirable, and various topical, oral, or injection-based cosmetic skin-lightening agents with different mechanisms of action are widely available across Asia. Objective. We sought to investigate the efficacy and safety of an oral glutathione supplement comprising L-glutathione (fermentation), ascorbic acid, alpha-lipoic acid, and zinc (as zinc aspartate) as a skin-lightening agent. Methods. This randomized, double-blind, controlled clinical trial was carried out at three teaching hospital-based dermatovenereology clinics in Indonesia. Participants were randomized to receive either the glutathione supplement or placebo capsules and were evaluated every four weeks over a 12-week study period. Total reduction in spot ultraviolet, spot polarization, and skin tone were measured and recorded using a Janus Facial Analysis System® (PIE Co., Ltd, Suwon-si, Gyeonggi-do, Korea). Results. Eighty-three participants, aged between 33 and 50 years, completed the study. Reductions in spot ultraviolet in certain subgroups, spot polarization, and skin tone were greater in the glutathione supplement group than in the placebo group, but the difference was not statistically significant. Both the glutathione supplement and placebo groups experienced only mild side effects in the first four weeks. Conclusion. The oral glutathione supplement was slightly beneficial for skin lightening in particular subgroups, but the results were not statistically significant. Mild and temporary side effects were reported. Further research is required to more fully evaluate the efficacy of this glutathione supplement as a skin-lightening agent. Keywords: Glutathione plus, skin-lightening agent, spot ultraviolet, spot polarization, skin tone For Asians, especially women with darker skin tones (Fitzpatrick Types IV and V), clear, bright skin is considered highly desirable. Various topical, oral, and injection-based cosmetic skin-lightening agents with different mechanisms of action are used widely across Asia, including hydroquinone, azelaic acid, kojic acid, mulberry, alpha-arbutin, beta-arbutin, glutathione, licorice root, papaya, vitamin A (e.g., retinol), vitamin B (i.e., niacinamide), and vitamin C.1,2 One of the widely used systemic agents is glutathione, which is a thiol compound and a regulator of the melanogenic pathway in humans.3 Glutathione is an antioxidant found in the human body, contributing to drug and xenobiotic detoxification.3,4 It is known to be antimelanogenic, thereby associated with melanin production.5,6 It also inhibits tyrosinase activity and melanosome transfer from melanocytes to keratinocytes.4–8 Overall, it is suggested that glutathione might promote pheomelanin synthesis, inhibit intracellular melanogenic enzymes, and exhibit antioxidant and anti-aging effects.3 As demonstrated in in-vitro experiments, glutathione is associated with melanogenesis. Its various mechanisms, including its antioxidant effects, the stimulation of pheomelanin synthesis instead of eumelanin, and interference with intracellular trafficking of melanogenic enzymes, contribute to its antimelanogenic properties.3 Hence, through the histopathological examination of melanocyte activity, location of melanin pigment deposition, and response after therapy, we can determine the effects of glutathione on skin color.6,9 However, Arjinpathana and Asawanonda1 reported many contradictory results regarding the efficacy and safety of glutathione as a skin-lightening agent. Therefore, glutathione is often combined with other compounds, such as ascorbic acid (vitamin C), alpha-lipoic acid (ALA), and zinc salts, in a cosmetic or skincare product to maximize the result. Similar to glutathione, vitamin C and ALA are also potent antioxidants that have numerous attractive features for use in cosmetic and dermatological products, while zinc salts are widely used in cosmetic formulations and are often included as active or supportive ingredients in a wide range of formulations.10–12 In the present study, we aimed to evaluate the efficacy and safety of an oral glutathione supplement (Lynae® Mazthione; Mazta Farma, Indonesia)—comprising L-glutathione (fermentation), ascorbic acid, ALA, and zinc (as zinc aspartate)—as a skin-lightening agent in healthy Indonesian women, measured using a facial analysis system for assessment every four weeks over a 12-week period. Methods We conducted a multicenter, randomized, double-blind, controlled clinical trial at three dermatovenereology clinics in Indonesia—namely, Presidential-Army Central Hospital Gatot Soebroto in Jakarta, Dr. Wahidin Sudirohusodo Hospital in Makassar, and the Universitas Sumatera Utara Teaching Hospital in Medan. The sample size was calculated using a two-proportion formula. Participants. Ninety healthy individuals were enrolled in this study. Included participants were aged between 30 and 65 years with Fitzpatrick IV and V Skin Types and were working a maximum of eight hours per day in an office environment. All participants signed an informed consent form. Exclusion criteria included personal or familial history of skin cancer, especially melanoma; use of supplements containing glutathione and/or other antioxidants within one month prior to the study; usage of other skin-lightening agents within one month prior to the study; other dermatoses; pregnancy or breastfeeding; and allergic or other skin reactions to oral therapies. Procedures. Block randomization was carried out on participants receiving glutathione supplement or placebo capsules by a statistician who was not otherwise involved in this study. Blinding methods were followed for the participants, dermatologist/physicians, and phototechnicians. To ensure blinding, the containers were labeled A and B by a single, blinded pharmacist, who disclosed the codes only at the end of the trial. Glutathione supplement capsules contained 500mg of L-glutathione (fermentation) together with 250mg of ascorbic acid, 50mg of ALA, and 4mg (20mg) of zinc (as
Heterologous Type I Collagen as an Add-on Therapy to Narrowband Ultraviolet B for the Treatment of Vitiligo: A Pilot Study
J Clin Aesthet Dermatol. 2021;14(6):31–34. by Aikaterini Gkouvi, MD; Electra Nicolaidou, MD, PhD; Andreas Corbo, MD; Gennaro Selvaggi, MD; Antonis Tsimpidakis, MD; Styliani Mastraftsi, MD; and Stamatios Gregoriou, MD, PhD Dr. Gkouvi is in private practice in Thessaloniki, Greece. Drs. Nicolaidou, Tsimpidakis, Mastraftsi, and Gregoriou are with the First Department of Dermatology-Venereology, Faculty of Medicine at the National and Kapodistrian University of Athens in Athens, Greece. Dr. Corbo is in private practice in Rome, Italy and with the University of Tor Vergata in Rome, Italy. Dr. Selvaggi is with the Department of Plastic Surgery at the Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital in Gothenburg, Sweden. FUNDING: No funding was provided for this article. DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article. ABSTRACT: Background. There is still an unsatisfied need for new treatments for vitiligo with more rapid onset and long-term sustainability of repigmentation. Objective. We sought to evaluate the possible efficacy of heterologous type I collagen as an add-on therapy to narrowband ultraviolet B (NB-UVB) for the treatment of vitiligo. Methods. Five patients with non-segmental vitiligo older than 18 years with bilateral and approximately symmetrical vitiligo lesions that did not evolve in size for at least six months were included. All vitiligo lesions were treated with NB-UVB therapy according to the Vitiligo Working Group recommendations. Two selected nonfacial lesions of each patient were also treated with intradermal injections of heterologous type I collagen (HTIC) every two weeks. Repigmentation of HTIC plus NB-UVB-treated lesions and their symmetrical counterparts treated just with NB-UVB was evaluated at baseline and Week 12. Results. Repigmentation of the HTIC-injected lesions started after the first treatment session in three cases and after the second session in two cases. After six sessions (Week 12), the mean repigmentation rate was 70.5 percent (95% confidence interval:0.569–0.841) in the NB-UVB plus HTIC treatment group versus 16.5 percent (95% confidence interval: 0.137–0.192) in NB-UVB treatment group (p=0.0006, paired t-test). Conclusion. Although the number of patients treated with the combination treatment was limited in our study, our results suggest that the addition of HTIC to NB-UVB therapy might offer a more rapid onset of repigmentation in patients with vitiligo. Keywords: Vitiligo, heterologous type I collagen, narrowband ultraviolet B, phototherapy, collagen, ultraviolet Vitiligo is a relatively common, acquired disease characterized by a progressive loss of functional melanocytes, which results in the appearance of well-circumscribed white macules and patches on the skin. Several mechanisms to date have been investigated to explain melanocyte destruction, including genetic and autoimmune factors, oxidative stress, inflammatory mediators, and melanocyte detachment mechanisms.1 However, these theories are insufficient to provide an undisputable mechanism of pathogenesis for all vitiligo phenotypes. Consequently, an “integrated theory” suggests that multiple mechanisms might work jointly in vitiligo to contribute to the destruction of melanocytes, ultimately leading to the same clinical result. Although a variety of treatments for the repigmentation of vitiligo lesions is available, none effectively promote complete and long-lasting repigmentation. Narrowband ultraviolet B phototherapy (NB-UVB) has been established as a safe and efficacious treatment for generalized nonsegmental vitiligo.2 However, the response to NB-UVB varies among patients and repigmentation might only appear after several months of treatment. Thus, the combination of NB-UVB and another treatment modality could be used in an effort to achieve faster and greater repigmentation. The promotion of melanocyte proliferation and melanogenesis enhancement has been suggested as a prospective vitiligo therapeutic strategy and therapeutic modalities such as platelet-rich plasma intradermal injections have been used in the treatment of vitiligo, with promising results.3 Furthermore, the disappearance of melanocytes has been suggested to be the final step of a complex scenario of deregulated biological events involving keratinocytes and fibroblasts as well.4 Heterologous type I collagen (HTIC) has been shown to promote cell and fibroblast proliferation and improve cutaneous extracellular matrix metabolism.5,6 Thus, intradermal injections of HTIC may influence the repigmentation process in vitiligo lesions. The objective of this pilot case series was to evaluate the potential synergistic effect of HTIC intradermal injections in combination with NB-UVB in stable, nonsegmental vitiligo. Methods Five female patients with stable nonsegmental vitiligo were included in this study. Study inclusion criteria were age older than 18 years, bilateral and symmetrical vitiligo lesions, presence of lesions that did not evolve in size for at least six months, no new lesions appearing during the study period, lack of koebnerization, and no history of keloids or hypertrophic scarring. All patients had been previously treated with topical treatment, including topical potent steroids and calcineurin inhibitors, with minimal or no response. A three-month washout period from any therapy was undertaken before study enrollment. All patients showed a willingness and ability to comply with the study requirements, and signed a written informed consent form. All vitiligo lesions were treated with NB-UVB therapy according to the Vitiligo Working Group recommendations.2 The initial dose was at 200mJ/cm2, with a subsequent increase of 10 to 20 percent per session. Sessions were held three times per week for 12 weeks (n=36 exposures total). The dose was individualized for each patient following the development of mild erythema. Two selected nonfacial lesions of each patient were additionally treated with intradermal injections of HTIC (Linerase®; Euroresearch, Milano, Italy). Linerase® is the commercial brand name of 100-gr micronized sterile powder of HTIC in vials for injectable use, obtained by type I collagen extracted from equine tendons. Tripeptides obtained from the polymer hydrolysis are composed of proline, hydroxyproline, and glycine. Each of the treated lesions had an approximately symmetrical counterpart lesion that was treated with only NB-UVB. Patients completed a total of six HTIC injection sessions over a period of three months. Patients were followed up with for 12 months after the last NB-UVB session. For each HTIC session, 100mg of HTIC (micronized, sterile powder dissolved in 4.5mL of normal saline [0.9% sodium chloride solution]) and 0.5mL of lidocaine were injected into the randomly chosen affected areas. The infiltration pattern that was followed was to inject 0.1mL of this solution intradermal
A Retrospective Study of 3,000 Indian Patients with Vitiligo Treated with Phototherapy or Topical Monotherapy
J Clin Aesthet Dermatol. 2021;14(2):46–49. by Jagdish Sakhiya, MD; Dhruv Sakhiya, MBBS Student; Neha Virmani, MBBS, MD, DNB; Trusha Gajjar, DVD; Jitesh Kaklotar, DDV; Ravi Khambhati, MBBS, DVD; Feral Daruwala, MPharm; and Nimish Dudhatra, MSC CR Drs. J. Sakhiya, Virmani, Gajjar, Kaklotar, Khambhati and Mr. Daruwala and Mr. Dudhatra are with Sakhiya Skin Clinic Pvt. Ltd. in Surat, Gujarat, India. Dr. D. Sakhiya is with B. J. Medical College in Ahmedabad, Gujarat, India. FUNDING: No funding was provided for this article. DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article. ABSTRACT: Background: Vitiligo-affected individuals, especially patients with darker skin tones, can suffer from negative psychosocial impacts due to unpredictable development of the condition and perceived cosmetic concerns. However, given that spontaneous repigmentation can be gained in vitiligo, many patients ask for treatment due to these cosmetic concerns. In the literature, only a few studies have been documented focusing on the outcome of various treatment modalities for vitiligo. Objective: This article highlights the retrospective response of various treatment modalities in Indian patients with vitiligo. Methods: A retrospective chart review was performed from July 2017 to August 2018 at our private dermatology clinic. A total of 3,000 patients were enrolled in this observational study. Patient characteristics and details of phototherapy (psoralen and ultraviolet A, narrow-band ultraviolet B, excimer laser) were noted as per a predefined format. The clinical response was evaluated as a marked response, defined as repigmentation in more than 75% of the initial lesional area. Results: In the present study, 1,996 patients received phototherapy and 1,004 patients were treated with topical monotherapy. Patients treated with phototherapy only and those treated with a combination of phototherapy and topical agents showed significantly higher clinical response rates relative to patients treated with topical monotherapy only (marked response rate: 47.8% vs. 8.7%; P<0.001 and 23.4% vs. 8.7%; P<0.001). Disease subtype predominately affected the treatment response. Conclusion: In Indian patients with vitiligo, phototherapy appears to be an effective treatment option for both focal and vitiligo vulgaris. Due to its reliability and minimal side effects, it can be considered a preferable treatment modality for vitiligo. KEYWORDS: Excimer laser, focal vitiligo, narrowband UVB ultraviolet A, psoralen, topical therapy, vitiligo vulgaris Vitiligo is a pigmentary disorder of the skin characterized by circumscribed depigmented macules and patches. The progressive and selective destruction of melanocytes resulting in partial to complete loss of pigmentation is the main mechanism involved in its pathogenesis. It affects 0.5 to 2 percent of the entire population worldwide and usually occurs in childhood or young adulthood. Many studies have reported an onset of disease before the age of 20 years in around half of patients. Although vitiligo may be more evident in patients with darker skin, the condition has no racial or ethnic predilection.1 Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis that may occur due to genetic as well as nongenetic factors. Even though several theories—including autoimmune mechanisms, cytotoxic mechanisms, intrinsic melanocyte defects, oxidant–antioxidant mechanisms, and neural mechanisms—have been proposed for its pathogenesis, the precise cause remains unknown.2 The advent of various treatment modalities in vitiligo—including phototherapy (psoralen and ultraviolet A [PUVA], narrowband ultraviolet B [NBUVB], and 308-nm excimer laser), topical therapy (topical corticosteroids, topical vitamin D3 analogs, and topical calcineurin inhibitors), and surgical therapy (suction blister grafts, split-thickness grafts, and miniature grafts)—has dramatically changed the dilemma regarding the selection of the proper treatment approach. As per recently published studies, topical corticosteroids are the preferred agents for management of localized vitiligo and phototherapy is a good alternative for generalized vitiligo.3,4 However, inconsistencies in study designs and outcome measures are major drawbacks in these studies. To date, no definitive treatment algorithm has yet been established for this condition. Further, variations in patient’s characteristics, including skin color, age, disease duration, and the extent and type of vitiligo may lead to a discrepancy in treatment response. It is, therefore, essential to gather sufficient evidence to establish a standardized treatment protocol.5 This study was carried out with the aim to assess the response to various types of treatment modalities in 3,000 Indian vitiligo patients. Methods This study was a retrospective observational study carried out from July 2017 to August 2018 at our private dermatology clinic. The study was conducted in accordance with the 1975 Declaration of Helsinki. Written informed consent was obtained before enrollment. In total, 3,000 patients with signs of vitiligo were enrolled in the study, regardless of sex or age. Study participant characteristics. The patients’ characteristics (age, age at onset, duration, sex, family history, comorbidities, disease localization, disease subtype, halo nevi, Koebner phenomenon, leucotrichia) and the treatment course were recorded. Apart from these, laboratory results, including thyroid function tests (thyroid-stimulating hormone, free thyroxine, antithyroglobulin antibodies, and antithyroid peroxidase antibodies) and the presence of other autoantibodies, were also assessed. Phototherapy. When phototherapy (PUVA, NBUVB, excimer laser) was used, the modality, duration of treatment, frequency, initial dose, total amount of irradiation, adverse events (AEs), and concomitant use of topical therapy (e.g., corticosteroids, calcineurin inhibitors, or vitamin D3 analogs) were recorded. The mean initial doses were 0.14 J/cm2 for PUVA, 0.28 J/cm2 for NBUVB, and 0.14 J/cm2 for excimer laser therapy. The optimal maintenance dose was set below the minimal erythema dose. Topical/oral psoralen was applied before ultraviolet A exposure. Topical treatment over six months either as the monotherapy or together with phototherapy was taken into consideration. Clinical outcomes. Clinical outcomes were evaluated using the following repigmentation grading: no response, mild response (<25% repigmentation), moderate response (25%–50% repigmentation), good response (50%–75% repigmentation), and marked response (>75% repigmentation).6 Statistical analysis. Data were analyzed using the Statistical Package for the Social Sciences version 21 (IBM Corporation, Armonk, New York) at the significance level of 0.05; quantitative data were expressed as mean ± standard deviation values and categorical data were presented as frequency (percentage) values. The chi-squared test (in the case of sample size >1,000) and Fisher’s exact probability test (in the case of sample size <1,000) were used for the analysis of frequencies.
Tolerability of Photodynamic Therapy Using 10% 5-Aminolevulinic Acid Hydrochloride Gel for Treating Actinic Keratoses on Surface Areas Larger than 75cm
J Clin Aesthet Dermatol. 2020;13(9):45–48 by Angela Yen Moore, MD and Stephen Moore Dr. Moore is with the Arlington Research Center in Arlington, Texas, Baylor University Medical Center in Dallas, Texas, and University of Texas Medical Branch at Galveston in Galveston, Texas. Mr. Moore is with the Arlington Research Center in Arlington, Texas. FUNDING: The authors received partial funding from Biofrontera, Inc., for retrospective chart review, data analysis, and manuscript preparation. DISCLOSURES: AY Moore has received funds as consultant and clinical study investigator for Biofrontera. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. ABSTRACT: Background: Photodynamic therapy (PDT) is a well-known treatment modality for actinic keratosis (AK). The largest surface area approved by the FDA is 20cm2 with 10% 5-aminolevulinic acid hydrochloride gel (10% ALA gel). Objective: This retrospective study assessed the tolerability of PDT with 10% ALA gel in areas ranging from 75cm2 to 300cm2. Method: The medical records of 203 patients with AKs treated with 376 PDT sessions using 10% ALA gel were reviewed. Face and ears were incubated with 10% ALA gel for 60 minutes without occlusion while all other areas were incubated for 90 minutes with plastic wrap occlusion followed by 10J/cm2 blue light. Patients were given specific post-PDT care directions. Patient outcomes data was collected. Results:Skin irritation was reported in 27 (7%) PDT sessions in 25 patients (12%). These occurred primarily on the face (n=17), hands (n=4,) and scalp (n=3). Of the 349 PDT treatments (93%) without irritation, these subjects reported adherence to a specific post-PDT regimen using zinc oxide and healing creams for 48 hours. Limitations: This was a retrospective study observing safety and tolerability. Clearance data was not collected. Conclusions: Based on this retrospective observational case series, PDT with ALA gel appears to be safe for treating patients with AKs covering surface areas 75 to 300cm2. Irritation might be mitigated by post-PDT care regimens. Keywords: Actinic keratosis, photodynamic therapy, retrospective study, 5-aminolevulinic acid gel, safety, tolerability Actinic keratoses (AK) are precancerous lesions that generally result from excessive exposure to ultraviolet light, especially sun-exposed areas of fair-skinned individuals.1 Early treatment of AKs might prevent progression to invasive squamous cell carcinomas.2 A meta-analysis of 25 studies reviewed the efficacy of current therapies for AKs in 5,562 patients.3 Treatments included photodynamic therapy (PDT), cryotherapy, imiquimod, diclofenac, fluorouracil, and ingenol mebutate. Typical adverse events included application-site erythema, burning, pain, scaling, and crusting. The mechanism of PDT involves the application of a photosensitizing agent followed by irradiation with light of an appropriate wavelength. The two most frequently used photosensitizers in dermatology are the pro-drugs methyl-aminolevulinate (MAL) and 5-aminulevulinic acid (ALA gel), which are preferentially absorbed into AK lesions metabolized into the active ingredient protoporphyrin which is activated by a light source.4 The subsequent generation of reactive oxygen species results in targeted cell death.5 Protoporphyrin has maximum absorption efficiency for blue light while red light provides maximum tissue penetration.4 Interest in field cancerization has increased because subclinical AK lesions can be found by histology in areas surrounding visible AKs.6 PDT with ALA gel is approved by the United States (US) Food and Drug Administration (FDA) for actinic keratosis in field-directed treatment areas measuring 20cm2 or smaller. Pivotal trials treated fields of cancerization with ALA gel over areas approximately 20cm2.7 Following one or two treatment sessions with a 635nm red light, 91 percent of those subjects achieved complete lesion clearance after three months. Complete clearance was maintained in 63 percent of subjects at 12 months following field application.7 Dermatologists in the US often face the challenge of patients with AKs on surface areas larger than 20cm2 that need treatment, but little patient-outcome data exists related to tolerability in larger treatment areas or with blue light illumination. This retrospective study assessed the safety of PDT when 10% ALA gel was applied to AKs in areas of field cancerization between 75cm2 and 300cm2. Methods This study was conducted in accordance with the principles of the Declaration of Helsinki and the principles of Good Clinical Practice and satisfied all applicable regulatory requirements, per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines.8 The protocol for this study was approved by Schulman IRB, Columbia, MD (#201707236). The medical records of 203 patients with AKs treated with 376 PDT sessions using 10% ALA gel (Biofrontera, Inc., Woburn, Massachusetts) in a single dermatology clinic in North Texas between April 2017 and May 2018 were reviewed. Planned treatment areas were degreased robustly with acetone-soaked 4×4 gauze in all patients and then debridement was performed on hyperkeratotic lesions. A full tube (200g) of 10% ALA gel was then applied to estimated surface areas of 265cm2 on full face and ears (Face), 130cm2 on bilateral dorsal hands (Hands), 230cm2 on bilateral dorsal wrists to elbows (Arms), 150cm2 on scalps (Scalp), 150cm2 on decolletés (Chest), 75cm2 on anterior or posterior necks (Neck), 300cm2 on bilateral shins or calves (Legs), and 300cm2 on upper backs (Back) (Table 1).9 The face and ears were incubated with 10% ALA gel for 60 minutes without occlusion, while other anatomical areas were incubated for 90 minutes with plastic wrap occlusion. Patients were instructed to stay within the building but could walk around inside the covered atrium or office building during their incubation period. Illumination was performed with 10J/cm2 blue light (417nm blue light for a duration of 16 minutes and 40 seconds) (DUSA Pharmaceuticals, Inc., Wilmington, Massachusetts). Immediately after illumination, a specific post-PDT regimen to expedite healing and decrease irritation was recommended. This regimen included a physical sunblock with >10% zinc oxide simultaneously with healing creams containing zinc and/or hyaluronic acid, which were applied every two hours during waking hours by the patient for 8 to 96 hours following PDT treatment. Patients were advised to avoid prolonged sunlight and tanning beds for 48 hours after PDT and to adhere to the post-PDT regimen even
What’s New in the Medicine Chest: An Update on the Latest Developments in Nonsteroidal Topical Therapy for Atopic Dermatitis
J Clin Aesthet Dermatol. 2020;13(5):44–48 by James Q. Del Rosso, DO, FAAD, FAOCD Dr. Del Rosso is Research Director at JDR Dermatology Research in Las Vegas, Nevada; is with Thomas Dermatology in Las Vegas, Nevada, and is an adjunct clinical professor of dermatology at Touro University Nevada in Henderson, Nevada. FUNDING: No funding was provided for this study. DISCLOSURES: Dr. Del Rosso, in relation to this subject area, is an advisor, research investigator, and/or speaker for Almirall, Anaptys Bio, Arcutis, Botanix, Dermavant, Dermira (Lilly), Encore, Galderma, Incyte, La Roche Posay, LEO Pharma, MC2, Menlo Therapeutics, Ortho Dermatologics (Bausch), Pfizer, Ralexar, Regeneron, Sanofi/Genzyme, Sonoma, and Sun Pharma. He is the sole author of this article and has not received any form of compensation related to writing or publishing this article from any pharmaceutical or device company or from any of their affiliated agencies. ABSTRACT: The author provides a thorough review of the latest topical treatment approaches for atopic dermatitis. Some agents are currently available in the marketplace, while others are in development. Modes of action, including phosphodiesterase-4 inhibition, aryl hydrocarbon receptor activation, and Janus kinase inhibition are discussed. Emphasis is placed on therapeutic approaches related to modes of action, with clinical data included. Keywords: Atopic dermatitis, phosphodiesterase-4, crisaborole, aryl hydrocarbon receptor, Janus kinase inhibitors Atopic dermatitis (AD) is a common chronic and recurrent inflammatory skin disorder.1–3 AD usually starts during infancy or in very early childhood, progresses through later childhood and adolescence with periods of exacerbation and relative remission, and can persist into adulthood, presenting as eczematous dermatitis, localized and/or diffuse, with a variety of clinical characteristics.4,5 The variable clinical presentations of AD can include a broad range of diagnoses, such as chronic hand eczema, nummular eczema, prurigo nodularis, dyshidrotic eczema, eyelid dermatitis, lichen simplex, nipple eczema, and periumbilical pruritic papules.4–6 Genetic predisposition is a major associated factor for the development of AD and other atopic disorders, such as asthma, allergic conjunctivitis, and seasonal rhinitis.7 Importantly, AD is a heterogeneous disease state with multiple phenotypic expressions rooted in a multifactorial pathophysiology that are influenced by complex interactions between susceptibility genes, altered and impaired epidermal barrier function, environmental factors, variations in skin microbiologic flora (i.e., microbiome), and immunologic dysregulation involving multiple aspects and pathways of the immune system.7,8 Extensive research on the pathophysiology and treatment of AD has become a major priority in dermatology, as gains in our understanding of the mechanisms of atopic disease are leading to major advances in therapy that are more targeted in their approach.9–11 This article reviews new and emerging nonsteroidal topical treatment approaches in AD, with emphasis on agents that reduce cutaneous inflammation via mechanisms beyond moisturization and barrier repair and maintenance. Topical Phosphodiesterase-4 (PDE4) Inhibition Phosphodiesterases (PDEs) are a group of ubiquitous intracellular enzymes that are physiologically involved in maintaining a variety of functional processes in many organ systems, such as modulation of inflammation, blood flow, and neurologic functions.12 Phosphodiesterase-4 (PDE4) is found in a variety of cell types, including keratinocytes, inflammatory cells, and synovial cells, and converts cyclic adenosine monophosphate (cAMP) to adenosine monophosphate (AMP), with the relative balance between cAMP and AMP impacting directly on the expression of proinflammatory and anti-inflammatory mediators.12,13 Role of PDE4 in AD. The activity of PDE4 is a component of intracellular homeostatic balance that maintains normal physiologic function when operating without dysfunction. When cAMP levels are low, there is activation of nuclear factor kappa-B (NF-kappaB), which serves to increase proinflammatory cytokine production and suppress production of anti-inflammatory cytokines.14,15 In AD, there is overexpression of PDE4 in cutaneous cells and in peripheral blood cells, which leads to increased conversion of cAMP to AMP; overexpression of AMP creates an imbalance that promotes inflammation through increased proinflammatory cytokine expression.16–19 Topical crisaborole for AD treatment. Crisaborole is a topically applied, low-molecular weight molecule with favorable penetration into skin that selectively targets and inhibits PDE4. This leads to decreased production of AMP and suppression of inflammation via decreased proinflammatory cytokine production.16 Pharmacokinetic evaluation in pediatric and adult patients, including maximal use studies in pediatric cohorts, has demonstrated negligible systemic exposure; clinical studies have supported the absence of any systemic safety signals to date.16,20–22 Efficacy was confirmed with crisaborole 2% ointment applied twice a day for mild-to-moderate AD in patients older than two years of age in the original pivotal studies, with reduction in pruritus also established, and with a post-hoc analysis showing efficacy and favorable safety in all races and ethnicities.16,21–23 New data on crisaborole mode of action (MOA) in AD. More recently, a study was completed to more specifically examine the MOA of crisaborole using gene expression profiling, biomarker evaluation through testing of messenger RNA (mRNA) expression, histologic examination, immunohistochemical staining to assess immune cell infiltration, and determination of impact on skin water content and flux (e.g., transepidermal water loss [TEWL]).24,25 A Phase IIa, single-center, vehicle-controlled, intrapatient study was completed in adults (N=40) with mild-to-moderate AD. In randomized subjects, two target lesions were selected in an intrapatient (1:1) double-blind method to evaluate crisaborole 2% ointment versus vehicle ointment, each applied twice daily for 14 days to their respective target lesions; subsequently, crisaborole ointment was applied to all affected areas for 28 days in an open-label fashion. For biomarker analysis, punch biopsy specimens were obtained at baseline and Day 15, and were optional at Day 8 of the study. Study outcomes revealed several observed changes in the affected areas treated with crisaborole, which support findings from other clinical studies that showed the therapeutic benefits of crisaborole 2% ointment (Figure 1).24,25 Early improvement in lesional signs and symptoms of AD was noted with crisaborole versus vehicle, including reduction in pruritus as early as 24 hours after initial application. Based on results shown with genetic expression profiles, lesions treated with crisaborole demonstrated marked percentage improvement from baseline in lesional transcriptomic profiles, compared to vehicle, at Day 8 (91.15% vs. 36.02%, P<0.05), which were sustained until Day 15 (92.90% vs. 49.59%, P<0.05). From a clinical perspective, these results indicate application of crisaborole can convert the
Clinical Efficacy and Safety of 3DEEP Multisource Radiofrequency Therapy Combined with Fractional Skin Resurfacing for Periocular Skin Aging
J Clin Aesthet Dermatol. 2020;13(3):41–44 by Lin Gao, MD, PhD and Hanmei Kang, MD; Yan Li, MD; Meiheng Lu, MD; Wenting Song, MD; Yuanli Wang, MD; Kai Li, MD, PhD; Li Wang, MD; and Gang Wang, MD, PhD Drs. Gao, Kang, Lu, Song, Y. Wang, Li, L. Wang, and G. Wang are with the Department of Dermatology at Xi Jing Hospital of the Fourth Military Medical University in Xi’an, China. FUNDING: Shaanxi scientific research grant #2016KTZDSF02-05 and 2016SF-374 were awarded to Dr. G. Wang. DISCLOSURES: The authors have no conflicts of interest relevant to the content of this article. ABSTRACT: Background. The early signs of skin aging usually occur in the periocular region. Objectives. This retrospective analysis evaluated the efficacy and safety profile of a multisource 3DEEP radiofrequency (RF) technology (EndyMed, Caesarea, Israel) in combination with fractional skin resurfacing (FSR) for the treatment of periocular skin aging. Methods. A total of 15 patients with periocular aging underwent monthly treatment sessions of 3DEEP and FSR for three months. Sessions were administered at the Department of Dermatology at Xijing Hospital in Xi’an, China. Indices of skin moisture level, transepidermal water loss (TEWL), skin elasticity, wrinkles, pore size, and skin texture were determined before and after treatment using the Visia® (Canfield Imaging Systems, New Jersey), Multiprobe Adapter (CK, Cologne, Germany) and Antera3D® (Miravex, Dublin, Ireland) systems. Results. Skin moisture level, elasticity, wrinkles, pore size, and texture improved relative to baseline (p<0.01). There was no significant difference in TEWL before and after the treatments (p>0.05). Patient satisfaction was 86.67 percent. Patients experienced varying degrees of transient edema, erythema, scabbing, and occasional hyperpigmentation; all adverse effects resolved within 2 to 10 days post-treatment. Conclusion. ENDYMED 3DEEP in combination with FSR appears to be safe and effective in treating periocular skin aging. Randomized controlled trials with a larger patient group are needed to confirm our findings. KEYWORDS: Multisource phase-controlled radiofrequency, fractional radiofrequency, facial rejuvenation, 3DEEP The eyelid is one of the thinnest areas of skin on the human body.1 Early visible signs of facial aging usually appear first in the periocular region. Periocular skin aging is a result of collagen deficiency, shifting gravity, photoaging, and skin atrophy.1,2 Its clinical symptoms include local hyperpigmentation, volume loss, infraorbital hollow development, dynamic and static wrinkles, thinning of the eyebrows, and deepening of the superior sulcus. Treatment of the periocular region should be done cautiously due to thinness of the skin and close anatomic proximity to the eyeballs. Current treatment options include surgery, laser therapy, radiofrequency (RF) treatment, topical agents, chemical peels, and fillers.2 Each approach has advantages and disadvantages; for instance, filler injections can restore volume loss effectively, but results only last for 6 to 9 months.3 Fractional ablative lasers can resurface the skin, but are limited by the occurrence of prolonged edema and the development of hyperpigmentation.4 In the past decade, RF technology has demonstrated efficacy and safety for facial skin tightening.5 Compared to other methods, RF treatment provides several unique benefits to patients. RF noninvasively targets dermal collagen to induce collagen remodeling and formation by heating the tissue.6 In addition, the melanin content of the skin does not affect its outcomes.7 Further, it can penetrate deeply into the dermis and increase tissue volume.7 Finally, the results of RF treatment (i.e., skin tightening), can persist for 6 to 12 months.8,9 RF devices can involve monopolar, bipolar, multipolar, or multigenerator heating mechanisms.10 In monopolar RF devices, energy is released from a single electrode into the skin, which can be painful for patients, and active skin cooling is required during the process.11 In bipolar and multipolar RF, energy flows between two poles through the skin superficially, which might also require cooling during the process.5,10 The 3DEEP multisource RF technology (EndyMed, Caesarea, Israel) uses an array of electrodes driven by six independent phase-controlled RF generators.5 The 3DEEP multisource RF allows practitioners to control the energy flow with minimal side effects; thus, no active cooling is required. In this retrospective analysis, we evaluated the efficacy and safety of the 3DEEP platform in combination with fractional skin resurfacing (FSR) for the treatment of periocular skin aging. Materials and Methods Subjects. The present study was a retrospective analysis. Fifteen patients with periocular aging were treated with 3DEEP multisource radiofrequency and FSR in the Department of Dermatology at Xijing Hospital from April 2017 to September 2017. The subjects ranged in age from 35 to 60 years, with an average age of 43±0.5 years old. Clinical symptoms included periocular wrinkles, periocular hyperpigmentation, sagging eyelids, and ptosis. Exclusion criteria for treatment included pregnancy, skin ulceration, coagulation disorders, use of photosensitizing or anticoagulation agents, history of skin rejuvenation therapies, including botulinum toxin and filler injections, six months prior to the study, history of laser therapy or chemical resurfacing, pacemaker implantation, and systemic diseases including cardiovascular disease, epilepsy, active vitiligo, and psoriasis. The risk factors and potential contraindications to using this treatment were discussed with patients before informed consent was sought. Written consent forms were obtained from all patients prior to the study. Treatment and evaluation. The multisource 3DEEP RF treatment platform was used in this study. The periocular region of the patients was cleaned and first treated with the iFine handpiece (EndyMed, Caesarea, Israel) with energy fluences of 3 to 4 W, which facilitates skin tightening in periorbital areas. A total of 6 to 10 passes (each pass is equal to 30 seconds of RF emission) was performed, with 5% lidocaine gel applied to the area before treatment. A second treatment with FSR was performed one hour after the first treatment. The energy fluences were 4 to 6 W, and the pulse width was 20ms. Patients were counseled to use moisturizer and protect themselves from sun exposure the first three days after treatment. Patients underwent three treatment sessions at monthly intervals. Digitalized high-resolution photographs combined with data from the Visia (Canfield Imaging Systems, New Jersey), Multiprobe Adapter (CK, Cologne, Germany) and Antera3D (Miravex, Dublin, Ireland) systems were used to evaluate outcomes. Images were taken at baseline, immediately after treatment,
Safety and Efficacy of the Combination of 308-nm Monochromatic Excimer Light and Topical 0.1% Tacrolimus Ointment in Segmental Vitiligo: An Open-label Study
Background. Vitiligo is an acquired disorder characterized by depigmented macules or patches on the skin due to the loss of functional melanocytes. Segmental vitiligo (SV) is a subtype of vitiligo refractory to treatment.
Maui Derm Daily News: Highlights from Monday, January 27, 2020
Highlights from Monday, January 27, 2020 Acne and Rosacea 2020 New drugs, new data, and new insights into acne and rosacea—Maui Derm’s esteemed faculty shared their insights into the management of acne and rosacea. Lawrence Eichenfield, MD, presented on new therapies in acne. New therapies discussed by Dr. Eichenfield included trifarotene 50ug/g cream, which selectively targets retinoic acid receptor gamma. Research on trifarotene reviewed by Dr. Eichenfield showed significantly reduced inflammatory lesions on the face, back, shoulders, and chest compared to vehicle over the course of four weeks. Another treatment discussed was 4% minocycline foam, which demonstrated statistically significant reductions in inflammatory lesions, measured by a two-point or greater decrease in Investigator’s Global Assessment score. Clascoterone cream 1%, a first-in-class topical androgen receptor inhibitor, was also discussed, as well as a polymeric tazarotene 0.045% lotion, which Dr. Eichenfield reports performed better than the higher concentration tazarotene 0.1% cream, with fewer adverse events. Dr. Eichenfield also reviewed a treatment algorithm for acne fulminans and evolving research on the microbiome and acne. Jim Leyden, MD, presented on isotretinoin dosing for severe acne. Dr. Leyden shared the algorithm he uses when treating with isotretinoin, starting all patients first on a topical retinoid plus benzoyl peroxide; if after 3 to 4 months suppression of inflammation is not achieved, Dr. Leyden moves on to spironolactone 100mg to 200mg per day and oral contraceptives, then isotretinoin for female patients. For male patients, he prescribes to the highest dose of isotretinoin that does not yield side effects until acne is cleared; if the patient relapses, Dr. Leyden restarts isotretinoin. For minor recurrences in most patients, Dr. Leyden refers back to topical retinoids and benzoyl peroxide. Fernanda Sakamoto, MD, PhD, presented on devices for treating acne. Dr. Sakamoto reviewed photodynamic therapy (PDT) combined with red light, citing this as one of the most efficacious optical treatments for reducing acne by increasing the expression of TLR-2, which has been implicated in the inflammatory response against acne-related sebocytes, and reducing hyperkeratosis and sebum output. Dr. Sakamoto also reviewed common side effects to expect when treating acne with PDT, as well as developments in research on PDT from the past year. Guy Webster, MD, PhD, reviewed how different strains of Propionibacterium acnes appear to affect inflammatory and non-inflammatory acne lesions. Dr. Webster also discussed topics related to isotretinoin therapy, including muscle damage, lab monitoring, rare instances of resistance to isotretinoin and lesions refractory to isotretinoin, bowel disease, bone mineral density during isotretinoin therapy, spondyloarthropathy, possible problems with muscle surgery, and male fertility. Dr. Webster went on to review adalimumab for hidradenitis suppurativa (HS), describing it as the most effective therapy for HS so far, as well as future therapies for HS, including ustekinumab and JAK inhibitors. New and emerging acne therapies discussed by Dr. Webster include topical minocycline, topical androgen inhibitors, sarecycline, encapsulated benzoyl peroxide, and photodynamic therapy. Dr. Webster concluded his presentation with an overview of new rosacea therapies, including brimonidine, topical minocycline, and encapsulated benzoyl peroxide. Hot Topic—Regeneration 2020: The Science Beyond Rejuvenation Wm. Philip Werschler, MD/FAAD/FAACS provided attendees with a presentation on the vast and exciting topic of regenerative medicine, which uses the body’s own repair and regenerative mechanisms to replace diseased or injured tissues, and its potential applications in aesthetic dermatology. The explosion of basic science research over the last decade in the areas of body rejuvenation is now being translated into dermatology. Dr. Werschler shared how the evolving science of “regeneration” will impact aesthetic and medical dermatology in the future. Topics discussed included: Defining biocellular medicine, identifying goals of biocellular medicine, and classifying therapies that fall into this category The evolution of regenerative therapy development An extensive explanation of PRP and its mechanisms of action in regenerative medicine Advantages to using PRP and the many ways in which PRP can be used in a regenerative dermatology practice—including hair restoration, microneedling, scar management, wound healing, aesthetic rejuvenation, and male and female sexual wellness
Maui Derm Daily News: Highlights from Saturday, January 25, 2020
Highlights from Saturday, January 25, 2020 Dermatology in Review Hensin Tsao, MD, PhD, in his inimitable style, discussed the most important findings from the literature that will impact the future of dermatology. Notable papers discussed in Dr. Tsao’s vast presentation include: A randomized clinical trial published in JAMA, in which 24 volunteers were subjected to sunscreen formulations (two spray formulations, one lotion, one cream) containing varying concentrations of avobenzone, oxybenzone, octocylene, and ecamsule; 2mg/cm2 were applied to 75-percent BSA four times per day for four days. Blood samples were collected to determine maximum plasma concentrations and AUC. Oxybenzone exhibited the highest blood concentration and fastest absorption, and all sunscreens exceeded steady state 0.5 ng/ml. A randomized trial of four common field-directed treatment approaches for actinic keratosis (AK): 1) 5% fluorouracil cream; 2) 5% imiquimod cream; 3) methyl aminolevulinate photodynamic therapy (MAL-PDT); 4) 0.015% ingenol mebutate gel. The primary outcome of the study was the percent of patients who demonstrated a 75-percent or greater reduction in the number of AKs from baseline to 12 months after the end of treatment. Dr. Taso highlighted that 5%-FU appeared to be the most effective, with a comparatively good tolerability profile, and PDT was the most painful during treatment. Five-year follow ups on two major treatment standards for metastatic melanoma: 1) the COMBI trials, which examined 553 patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutation randomized to dabrafenib plus trametinib; and 2) a randomized controlled trial that examined melanoma treatments nivolumab and ipilimumab, alone and in combination with each other. A Phase III, double-blind, placebo controlled (N=165) trial that examined the selective kappa opioid receptor agonist difelikefalin, administered intravenously three times per week for 12 weeks, versus placebo for hemodialysis patients with pruritus; the primary outcome was the proportion of patients with an improvement of at least 3 points from baseline at Week 12 on the 24-hour Worst Itching Intensity Numerical Rating Scale (0=none, 10=worse). While Dr. Tsao pointed out the significant placebo effect that appeared to be present in this trial, he doesn’t rule out the importance of this new potential treatment for chronic uremic pruritus, considering there are no drugs currently approved by the US Food and Drug Administration for the condition. A multicenter Phase II study evaluating pembrolizumab in relapsed and refractory mycosis fungoides and Sezary Syndrome. Overall response rate in the study was 38 percent, which Dr. Tsao notes is favorable compared to other treatments; he also pointed out that the results were notably durable. A whole exome sequencing project to discover variants associated with central centrifugal cicatricial alopecia (CCCS) that found increased frequency of rare peptidyl arginine deiminase 3 (PADI3) variants among patients with CCCA compared to the general population A nationwide, population-based Korean cohort study that found a significant cancer-protective effect associated with vitiligo; Dr. Tsao explained that colorectal, lung, and breast cancers were most strongly associated with chemoprotection, while thyroid cancer was most strongly associated with increased risk In her update of pediatric dermatology, Dr. Friedlander began her presentation with the most recent guidelines of care for infantile hemangiomas (IH) from the American Academy of Pediatrics, including a review of how to choose among the currently available therapies for IH, including propranolol, topical timolol, intralesional triamcinolone, and oral steroids. Dr. Friedlander went on to discuss research on MEK inhibition as a way to improve symptom control in primary NRAS-driven central nervous system melanoma in children, as well as a case report of a giant congenital melanocytic nevus treated with trametinib. Dr. Friedlander moved on to a discussion of topical cannabis for epidermolysis bullosa, then touched on the new joint American Academy of Dermatology-National Psoriasis Foundation guidelines for psoriasis in pediatric patients. An extensive discussion of the latest research on sunscreen absorption rounded out her informative presentation. New Drugs and Therapies 2020 The “Ted and Neal Show” once again entertained and educated meeting attendees about new drugs and therapies in dermatology and how we will be using them in 2020. Ted Rosen, MD and Neal Bhatia, MD, discussed a variety of new, emerging, and noteworthy drugs and therapies in their presentation, including topical retinoids for acne, such as trifarotene 0.005% cream, tretinoin 0.05% lotion, and tazarotene 0.045% lotion, the topical antiandrogen clascorterone 1% cream for acne, and minocycline 4.0% foam for acne. In addition, the presentation covered emerging research on the efficacy of VP-102 0.7% topical cantharidin in a single-use vial for the treatment of molluscum contagiosum, as well as an intravenous formulation of cetirizine for acute urticaria and betamethasone dipropionate 0.064% plus calcipotriene 0.005% for plaque psoriasis. The first FDA-approved vaccine for the prevention of the Ebola virus disease, a critical milestone in public health preparedness, was discussed, along with microwave therapy for cutaneous human papilloma virus infection. Following this, the presentation touched on a microencapsulated benzoyl peroxide 5% formulation for inflammatory lesions of rosacea and microencapsulated benzoyl peroxide 3% with tretinoin 0.1% for acne. After, the pair discussed afamelanotide, an analogue of alpha-melanocyte-stimulating hormone, which produces tanning-like pigmentation and is the first treatment approved to increase pain-free light exposure in patients with erythropoietic protoporphyria. The presentation wrapped up with a discussion of sofpironium bromide gel for hyperhidrosis and 5-aminolevulinic acid and photodynamic therapy for actinic keratosis on the upper extremities. Cutaneous Oncology, Part 1 Presentations from George Martin, MD, Ted Rosen, MD, Eggert Stockfleth, MD, and Chrysalyne Schmults, MD, MSCE guided attendees through new therapies in actinic keratosis, ways to optimize the treatment of AKs and non-melanoma skin cancer, including advanced-stage disease. In his presentation, Dr. Martin explained to attendees the merits of adding calcipotriene 0.05% to 5% fluorouracil (5-FU) in equal parts to improve the efficacy of treating AKs compared to treating with 5% 5-FU alone. Also discussed was tirbanibullin, a new topical field therapy for AKs currently awaiting approval. Tirbanibullin targets tubulin and the Src growth pathways in AKs. Dr. Martin pointed to research in which tirbanibullin was applied twice daily for five days; 50 percent of patients achieved total clearance