Volume 16 | Issue 12
Effectiveness of the Mohs and Close Technique in Increasing the Efficiency of a Mohs Micrographic Surgery
Sailesh Konda MD,a,b Joseph Francis MD,a,c Vishal A. Patel MDd|Editor’s note: JDD welcomes Letters to the Editor that discuss controversy surrounding a recently published article. Letters being considered for publication may be sent to the authors of the original article, who may be given the opportunity to reply. Letters will be published at the discretion of the Editors.
George F. Cohen MD and Christopher M. Wolfe DO|
Recalcitrant cutaneous sarcoidosis with perianal involvement is rare. To our knowledge we present the first documented case of cutaneous sarcoidosis with perianal involvement successfully treated with adalimumab.
J Drugs Dermatol. 2017;16(12):1305-1306.
Sheldon Bradshaw JD|No abstract details for the moment.
Upregulation of Extracellular Matrix Genes Corroborates Clinical Efcacy of Human Fibroblast-Derived Growth Factors in Skin Rejuvenation
Kuniko Kadoya PhD,a Elizabeth T. Makino BS CCRA MBA,a Lily I. Jiang PhD,b Michael Bachelor PhD,c Robin Chung BS,a Priscilla Tan BA,a Tsing Cheng PhD,a Gail K. Naughton PhD,d and Rahul C. Mehta PhDa|
Skin care products may use various active ingredients to support skin rejuvenation including growth factors and other molecules that help to regenerate extracellular matrix (ECM) and promote skin repair. The biological effect of skin care products with a strong anti-aging claim was assessed in gene expression analyses using an in vitro human skin model. Application of products containing human fbroblast-derived growth factors resulted in signifcant upregulation of genes encoding ECM components including collagens and elas-tin. Human fbroblasts cultured under hypoxic conditions show increased gene expression of stem cell markers, and their conditioned media could possibly further support skin rejuvenation. Furthermore, a double-blind, randomized, placebo-controlled study was con-ducted in subjects with moderate to severe facial photodamage to assess the cosmetic clinical effcacy of a product containing human fbroblast-derived growth factors. The test product group demonstrated signifcantly greater reductions in the appearance of fne lines/wrinkles, coarse line/wrinkles, and overall photodamage, compared to the placebo group. Altogether, the results suggest that human fbroblast-derived growth factors support skin rejuvenation by stimulating dermal fbroblasts to generate ECM.
J Drugs Dermatol. 2017;16(12):1190-1196.
Lawrence Transfer Factor: Transference of Specific Immune Memory by Dialyzable Leukocyte Extract from a CD8+ T Cell Line
Jason F. Wang BA,a Andrew J. Park BA,b Tina Rendini RN,c William R. Levis MD|
Lawrence transfer factor (TF) is defined as dialyzable leukocyte extract (DLE) that can transfer antigen-specific cell-mediated immunity from a person testing positive for the antigen in a delayed type hypersensitivity skin test manner to a person negative for the same antigen.
A recent article by Myles et al1 has identified a DLE isolated from an established CD8+ T cell line capable of transferring antigen-specific immunity. The DLE contains a portion of the beta chain of the T cell receptor and additional nucleotide and protein factors that are being subjected to further modern biochemical analysis.
After months of study that included interviews of TF physician-scientists, we conclude that an antigen-specific TF exists for most, if not all, antigens. By working from a CD8+ T cell line with modern biochemical technology, it should be possible to identify and patent products capable of treating infectious diseases, antigen-responsive cancers, and autoimmune disorders.
J Drugs Dermatol. 2017;16(12):1198-1206.
Combining Topical Psoriasis Treatment to Enhance Systemic and Phototherapy: A Review of the Literature
Jerry Bagel MD,a and Linda Stein Gold MDb|
Psoriasis is a chronic inflammatory skin disease that affects millions of people in the United States as well as worldwide. While there is currently no cure for psoriasis, many treatment options are available. Topical therapies are the mainstay for the majority of patients who have limited or mild psoriasis. Among these medications, topical vitamin D analogs (eg, calcipotriene) and corticosteroids (eg, betamethasone), and these drugs in combination, are the most widely prescribed psoriasis drugs and are the cornerstone of topical therapies. For patients with more severe disease, phototherapy, conventional systemic agents, and biologics are often indicated. Currently, the goal of treatment is to control the clinical symptoms of the skin, reduce systemic disease potential, and improve the patient’s quality of life. Despite the availability of various therapeutic options for psoriasis, many patients go untreated, and even among those who are treated, many do not achieve complete resolution of the disease. The new consensus is to treat to a target of 1% or less of body surface area involvement. Innovative treatment strategies are needed to meet this goal and patients’ desire to achieve clear skin. Combination therapies are widely used by physicians, and adjunctive topical therapies used with other antipsoriatic regimens have been demonstrated to provide many clinical benefts. This article reviews the most recently published clinical evidence of adjunctive use of topical agents with biologics, conventional systemic agents, and phototherapy, to better establish the role of topical agents in combination therapy for the treatment of psoriasis.
J Drugs Dermatol. 2017;16(12):1209-1222.
Varun Kalhana and Neil Sadick MDb|
Biologic drugs, a novel class of agents engineered to target specifc mediators of infammation, and small-molecule inhibitors that pen-etrate the cell membrane to interact with targets inside a cell represent the cutting-edge of pharmacological biomedical therapeutics. Clinical studies have already demonstrated the effectiveness of this new generation of drugs in treating a variety of medical illnesses and conditions that were refractory to traditional treatments. This review aims to describe the latest available or currently in-develop-ment drugs, biologic agents, and small molecule inhibitors for treatment of psoriasis, rosacea, alopecia areata, and atopic dermatitis.
J Drugs Dermatol. 2017;16(12):1224-1228
A Novel Multifactorial Approach to Developing Mild Laundry Detergents and Assessing Their Relative Mildness
Joseph F. Fowler Jr. MD,a Matthew J. Zirwas MD,b Lisa Napolitano BS,c Meghan Russell BS,c and Janet Coope-Epstein PhDc|
INTRODUCTION: Dermatologists are becoming more aware of the irritant and allergic potential of laundry detergents that incorporate harsh surfactants and potentially sensitizing ingredients. It is difficult however for the physician to distinguish one laundry detergent from another because the only distinguishing feature advertised tends to be the lack of dyes and fragrances.
DESIGN: A new objective method was developed for measuring the harshness of laundry detergents using a three-pronged laboratory testing approach consisting of zein, corneosurfametry, and cytokine testing. Combing these methods, a Detergent Mildness Index was created which conveniently provides a single value by which products can be compared.
Results: A new mild laundry detergent was formulated with ingredients carefully selected by dermatologists who are experts in con-tact dermatitis. The irritancy potential of the formula was measured using the Detergent mildness index score. Compared to 11 other commercial laundry detergents marketed for sensitive skin, the new formula is measurably the mildest formula.
Discussion: The Detergent Mildness Index provides dermatologists with an objective method to compare commercial laundry deter-gents. Currently the only method available is patch testing, this new test is able to more finely differentiate between products and thus enables more informed recommendations on laundry detergent choices for their patients with sensitive skin.
J Drugs Dermatol. 2017;16(12):1235-1239.
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Real-World Clinical Experience With Apremilast in a Large US Retrospective Cohort Study of Patients With Moderate to Severe Plaque Psoriasis
April Armstrong MD MPH,a and Eugenia Levi PharmDb|
OBJECTIVE: To examine real-world use and patient outcomes with apremilast, an oral PDE4 inhibitor, in the dermatology practice set-ting for treatment of patients with moderate to severe plaque psoriasis.
METHODS: This retrospective, multicenter, longitudinal, observational cohort study used Modernizing Medicine’s electronic medi-cal record (EMR) database of >5000 US dermatology providers. There were 7517 adults aged ≥18 years with a psoriasis diagnosis (ICD-9, ICD-10) who received apremilast therapy from October 1, 2015, to January 31, 2016, and were included in effcacy and safety analyses. Among patients who switched from non-apremilast to apremilast monotherapy, the majority (74.2%) switched from prior topical treatment.
RESULTS: At apremilast initiation, in systemic-naive and systemic-experienced patients, mean (SD) Physician Global Assessment (PGA) was 2.79 (0.13) and 2.48 (0.15); mean (SD) psoriasis-affected body surface area (BSA) was 17.85% (2.27) and 12.93% (2.59); and mean itch numeric rating scale (NRS; 0=no itch, 10=worst itch possible) score was 4.14 and 3.82, respectively. Within 6 months of apremilast initiation, PGA decreased (mean [SD]) in systemic-naive patients (−1.71 [0.19], P less than0.001) and systemic-experienced pa-tients (−1.02 [0.18], P less than 0.001); 26.8% (systemic-naive) and 25.5% (systemic-experienced) of patients achieved a PGA score of 0 or 1. Likewise, statistically signifcant reductions in BSA were noted in systemic-naive patients (~62% reduction from baseline; P less than 0.01) and systemic-experienced patients (~60% reduction from baseline; P=0.002). Mean itch NRS decreased to 2.38 in systemic-naive patients (P=0.139) and 0.0 in systemic-experienced patients (P=0.034). Of 160 patients with ≥1 assessment of patient-perceived overall treatment effectiveness, 138 (86.2%) strongly/somewhat agreed apremilast was effective in clearing their skin of psoriasis. For safety analyses, body weight was available in the EMR database and decreased in systemic-naive patients (−1.75 kg) and systemic-experienced patients (−1.09 kg).
Conclusions: Findings support the effectiveness of apremilast in patients with moderate to severe psoriasis in dermatology clinical practices. Patients perceived apremilast to be effective.
J Drugs Dermatol. 2017;16(12):1240-1245.
Cost Per Additional Responder Associated With Ixekizumab and Etanercept in the Treatment of Moderate-to-Severe Psoriasis
Steven R. Feldman MD PhD,a Shonda A. Foster PharmD MS,b Baojin Zhu PhD,b Russel Burge PhD,b,c Sarah Al Sawah PhD,b and Orin M. Goldblum MDb|
BACKGROUND: Newer psoriasis treatments can achieve greater levels of effcacy than older systemic therapies; however, current pso-riasis costs are substantial. We sought to estimate costs per additional responder associated with ixekizumab and etanercept, versus placebo, using effcacy data from phase 3 clinical trials (UNCOVER-2 and UNCOVER-3).
METHODS: In UNCOVER-2/UNCOVER-3, patients received subcutaneous placebo, etanercept 50 mg twice weekly (BIW), or ixekizumab one 80 mg injection every 2 weeks (Q2W) after a 160-mg starting dose. Twelve-week induction-phase Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100 response rates for ixekizumab, etanercept, and placebo were obtained from pooled data from the overall and United States (US) subgroup intention-to-treat (ITT) populations, and used to calculate numbers needed to treat (NNTs) to achieve one additional PASI 75, PASI 90, or PASI 100 response for ixekizumab Q2W and etanercept BIW versus placebo. Twelve-week drug costs per patient were calculated based on the UNCOVER-2/UNCOVER-3 dosing schedule and wholesale acquisition costs. Mean costs per additional responder for PASI 75, PASI 90, and PASI 100 for each treatment versus placebo were calculated for pooled UN-COVER-2/UNCOVER-3 overall and US subgroup ITT populations.
RESULTS: Pooled overall ITT population: costs per additional PASI 75, PASI 90, or PASI 100 responder were US $37,540, US $46,299, or US $80,710 for ixekizumab Q2W and US $57,533, US $120,720, or US $404,695 for etanercept BIW, respectively. US subgroup ITT population: costs per additional PASI 75, PASI 90, or PASI 100 responder were US $38,165, US $49,740, or US $93,536 for ixekizumab Q2W and US $69,580, US $140,881, or US $631,875 for etanercept BIW, respectively.
CONCLUSIONS: Twelve-week costs per additional responder were lower for ixekizumab Q2W than for etanercept BIW across all levels of clearance (PASI 75, PASI 90, and PASI 100) in the pooled UNCOVER-2/UNCOVER-3 overall and US subgroup ITT populations.
J Drugs Dermatol. 2017;16(12):1246-1252.
A Systematic Review of Lower Lip Anatomy, Mechanics of Local Flaps, and Special Considerations for Lower Lip Reconstruction
Stefanos Boukovalas MD, Alexis L. Boson BS, Joshua P. Hays BS, C. Helen Malone MD, Eric L. Cole MD, and Richard F. Wagner Jr. MD|
Reconstruction of defects of the lower lip can be very challenging. The aim of this review is to analyze the unique characteristics of lower lip anatomy and provide a systematic approach for lower lip reconstruction. A review of current literature was performed using the PubMed database. Articles analyzing the anatomic and histologic characteristics of the lower lip, mechanics of local faps, and different lower lip recon-struction techniques were included. Articles focused on lower lip reconstruction with free faps were excluded. The orbicularis oris has been described as the main supportive mechanism, however, a number of other structures have been shown to provide mechanical support to the lower lip, including septations of connective tissue extending from the epithelium to the orbicularis oris, a fbroelastic meshwork located in the mentolabial sulcus, and subdermal muscular fbers with dermal terminations in the area of the modiolus. Depending on the location, size, and depth of the wound, a number of reconstruction options are available. Preservation of the competency of orbicularis oris, relation-ship of the modiolus with associated muscles, and sensation, are critical components of functional reconstruction. Primary closure and local faps are assessed for these 3 components and analysis is provided. In conclusion, knowledge of the static and dynamic structural support of the lower lip, as well as the characteristics of different reconstructive options, is imperative for optimal functional and aesthetic outcomes.
J Drugs Dermatol. 2017;16(12):1254-1261.
"Deep Heating” Noninvasive Skin Tightening Devices: Review of Effectiveness and Patient Satisfaction
Suneel Chilukuri MD FAAD FASDSa and Jason Lupton MDb|
Non-surgical aesthetic devices intended for treatment of lax and loose skin have gained popularity due to their ability to non-invasively improve patient’s aesthetic condition and its low side effect profle. This study is intended to review available peer reviewed literature about Ultherapy, ThermaCool, and Exilis Ultra 360 non-invasive skin tightening devices to compare their treatment effcacy and patient subjective satisfaction.
J Drugs Dermatol. 2017;16(12):1262-1266.
Richard A. Pollak DPM and Carla Ilie BS|Background: Onychomycosis is a common disease that remains difficult to treat despite the introduction of new topical agents. Clinical trials on efinaconazole and tavaborole included 48 weeks’ daily treatment regimens with a 4-week follow-up. It has been suggested that either a longer treatment regimen or longer follow-up would lead to even better results, primarily due to the time taken for the diseased nail to grow out, especially in those patients with more severe disease.
OBJECTIVE: To investigate the impact of a longer follow-up period on the efficacy of efinaconazole 10% topical solution in patients with moderate-to-severe onychomycosis.
METHODS: Single center, open-labeled study in 23 subjects aged 18-80 years with a clinical and mycological diagnosis of moderate-to-severe dermatophyte toenail onychomycosis (40-75% clinical involvement). Subjects were treated with efinaconazole 10% solution, once-daily for 48 weeks, with two 12-week post-treatment follow-ups (at week 60 and 72). Primary efficacy endpoint was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture). Secondary endpoints included mycologic cure rates and treatment success (defined as those patients who had at least a 50% improvement in affected toenail from baseline).
RESULTS: Twenty-two subjects completed the study. Mean baseline age 59.4 years (range, 37-77), predominance of male subjects (73.9%). Median baseline severity 50% affected target toenail. At week 72, two subjects were complete cures and 56.5% of subjects achieved treatment success. There were no complete cures at week 48, but 39.1% achieved treatment success. Mycologic cure rates were 91.3% at week 48. Median percent affected target toenail reduced to 40%, and further to 25% (week 48 and 72, respectively). Treatment was well tolerated, with no adverse events related to medication.
CONCLUSIONS: This single-center phase 4 study supports previous data showing good efficacy and tolerability of efinaconazole in moderately severe onychomycosis. Continued reduction in disease severity post-treatment suggest that a longer follow-up of patients treated with efinaconazole would afford better efficacy results, as indicated by greater treatment success, and increase in number of subjects who became complete cures.
J Drugs Dermatol. 2017;16(12):1269-1273.
Patient Awareness of Local Drug Price Variation and the Factors That Influence Pharmacy Choice: A Cross-sectional Survey Study
Spencer D. Brodsky BS,a Olabola D. Awosika MD MS,b Misty G. Eleryan MD,a,b Monica Rengifo-Pardo MD,a,b Xiangyu Kuang MS,b Richard L. Amdur PhD,a,b and Alison Ehrlich MD MHSa,b|
Background: High out-of-pocket drug expenditures are increasingly common in dermatology. Patients may not be aware that prices vary among pharmacies and consequently may not shop for the lowest cost.
Objective: To determine what factors influence pharmacy choice and the effect of providing local prescription prices on pharmacy selection. We hypothesized that patients do not “shop around” due to lack of knowledge of price variation and would choose a pharmacy based on costs if educated on price disparity.
Methods: Between July and August 2016, we administered a cross-sectional anonymous survey to adults visiting four outpatient clinics at an academic tertiary care center in Washington, D.C. Participants answered questions before and after viewing a list of prescription drug prices from local pharmacies.
Results: 287 surveys were administered to a convenience sample of adults (age ≥ 18 and literate in English). Of the 287 participants, 218 fully completed the survey; 55.1% were women and 40.5% were over age 40. When considering a cost savings of $10-25, 65% would switch pharmacies if the distance were the same, and 21.3% would switch if the distance were 45-minutes further. After price education, fewer participants felt that drug price knowledge would ultimately influence pharmacy choice (P less than 0.0001). However, respondents’ intended frequency of researching price online, calling a pharmacy to ask about price, and comparing price between pharmacies before filling a prescription all increased, compared to prior self-reported frequencies (P less than 0.001). Specifically, participants with $75,000-$99,999 income were more likely to compare prices than those with income below $45,000 (odds ratio [OR], 4.62; 95% confidence interval [CI], 1.24-17.28)
Conclusion: In this study, pharmacy choice was more influenced by convenience than cost prior to drug price education. However, price education ultimately impacted intent to research prescription drug prices before selecting a pharmacy. Thus, knowledge of drug pricing may be useful in creating cost savings for patients.
J Drugs Dermatol. 2017;16(12):1274-1280.
Olabola Awosika MD MS,a Misty Eleryan MD,b Monica Rengifo-Pardo MD,a,b and Alison Ehrlich MD MHSa,b|
Mastocytosis is a disease characterized by the abnormal clonal proliferation of mast cells in skin and/or extracutaneous organs, often relating to activating mutations of c-KIT. Histopathology special stains, such as Giemsa, Leder, and Toluidine blue, are key for the diagnosis of cutaneous mastocytosis (CM). In adults, skin lesions can be associated with systemic disease. Tryptase is a diagnostic marker in mastocytosis and thought to reflect the burden of mast cell disease. In this report, we present a case of cutaneous mast cell disease with associated findings of elevated serum tryptase and mast cell infiltration of the bone marrow consistent with indolent systemic mastocytosis.
J Drugs Dermatol. 2017;16(12):1285-1287.
Kavita Darji BA and Nicole M. Burkemper MD|
Pityriasis folliculorum has been described as a dry type of rosacea with extensive proliferation of Demodex folliculorum in pilosebaceous follicles of the skin. This skin condition is frequently difficult to manage, with various treatment options showing mixed efficacy. Oral ivermectin, a macrocyclic lactone parasiticide with anti-inflammatory and anti-parasitic effects, is one of the leading treatment modalities for demodicosis. Topical ivermectin has recently been FDA approved as therapy for rosacea. We present the case of a woman with pityriasis folliculorum who showed significant improvement from using topical ivermectin with no adverse events related to treatment.
J Drugs Dermatol. 2017;16(12):1290-1292.
Gerald O’Daniel MD FACS|
Despite a well-established safety profile for poly-L-lactic acid (PLLA), known complications of nodules, papules and granulomas can occur. The author presents a case of late-onset facial nodules after treatment with PLLA dermal filler for facial volumization. The late-onset nodules appeared 16 months post-initial injection and were initially treated with intralesional steroids followed by 5-fluorouracil, and oral corticosteroids. It took over a year of treatment with oral corticosteroids and periodic intralesional steroid injections for the nodules to resolve. The author describes in detail the course of the nodules as well as the clinical management.
J Drugs Dermatol. 2017;16(12):1297-1299.