Volume 17 | Issue 3
Hugh M. Gloster Jr. MD|The following is a response to the Letter to the Editor by Konda, Francis, and Patel regarding the article “Mohs and Close” Technique (MCT) for selected cases to increase the efficiency of Mohs micrographic surgery.1,2 The letter raises questions about our utilization of MCT that require clarification.
Kim A. Papp MD PhDa and Mark G. Lebwohl MDb|BACKGROUND: The advent of biologics has improved patient outcomes in the treatment of moderate-to-severe psoriasis. The time it takes for patients to see clinically meaningful improvement is an important aspect of disease management. OBJECTiIVE: To review the clinical data on the use of biologics in moderate-to-severe psoriasis, identifying which biologics may offer the quickest results. METHODS: A review of the published and presented efficacy data on adalimumab, infliximab, ustekinumab, etanercept, brodalumab, ixekizumab, and secukinumab to estimate the time to achieve clinically meaningful outcome; defined as time for 25% of patients to achieve Psoriasis Area and Severity Index (PASI) 75, or a 50% reduction in mean baseline PASI. RESULTS: Clinically meaningful outcomes were achieved within 2-11 weeks with biologics. Calculated times for 25% of patients to achieve PASI 75 were 2.1 [95% CI 2.0-2.3] weeks (brodalumab), 2.4 weeks (ixekizumab), 3.0 weeks (high-dose secukinumab), 3.5 weeks (infliximab), 4.6 weeks (adalimumab and high-dose ustekinumab), 5.1 weeks (low-dose ustekinumab), 6.6 weeks (high-dose entanercept), and 9.5 weeks (low-dose entanercept). Calculated times for 50% reduction in baseline PASI were 1.8 [95% CI 1.7-1.9] weeks (brodalumab), 1.9 weeks (ixekizumab), 3.0 [95% CI 2.8-3.2] weeks (high-dose secukinumab), 3.5 weeks (adalimumab), 3.7 weeks (infliximab), 5.1 weeks (low-dose ustekinumab), 6.5 weeks (high-dose entanercept), and 10.9 weeks (low-dose entanercept). CONCLUSIONS: Brodalumab may have the most rapid onset of action of any biologic therapy used in psoriasis. Similar results were seen with both outcome measures and will have important implications in psoriasis management.
J Drugs Dermatol. 2018;17(3):247-250.
Sam Hanna MD DABD,a Anneke Andriessen PhD,b Jennifer Beecker MD CCFP (EM) FRCPC DABD,c Martin Gilbert MD FRCPC,d Eric Goldstein MD FRCPC,e Sunil Kalia MD FRCPC,f Aaron King MD FRCPC,g John Kraft MD,h Carrie Lynde MD FRCPC,i Davindra Singh MD FRCPC,j Irina Turchin MD FRCPC,k and Catherine Zip MD FRCPC l|BACKGROUND: Recently, experience and knowledge have been gained using effective topical treatment for onychomycosis, a difficult-to-treat infection. METHODS: This project aims to help understand and improve patient-focused quality of care for fungal nail infections. A panel of dermatologists who treat onychomycosis convened on several occasions to review and discuss recent learnings in the treatment of onychomycosis. The panel developed and conducted a survey on diagnosis, treatment and prevention, discussed the results, and provided recommendations. RESULTS: The survey was sent out digitally to the Canadian Dermatology community. Ninety-two dermatologists completed the questionnaires, which were included in the analysis. The survey respondents and panel members agreed that the diagnosis of toe onychomycosis should be confirmed with a positive microscopic examination for fungus or a positive mycological culture when oral therapy and/or topical treatment is prescribed, except when it is not clinically feasible, in which case topical therapy could be started based on clinical presentation. The panel and survey respondents also agreed that treatment is to be based on percentage of nail involvement: less than 20%=topical efinaconazole; 20%-60%=topical efinaconazole±oral terbinafine (for greater than 3 nails); greater than 60%=oral terbinafine±topical therapy. CONCLUSIONS: The current treatment paradigm for onychomycosis may have shifted from mainly oral antifungals to topical treatment, improving patient-focused quality of care.
J Drugs Dermatol. 2018;17(3):253-262.
Efficacy and Safety of Adapalene 0.3%/Benzoyl Peroxide 2.5% Gel Plus Oral Doxycycline in Subjects With Severe Inflammatory Acne Who Are Candidates for Oral Isotretinoin
James Q. Del Rosso DO,a Linda Stein Gold MD,b Sandra Marchese Johnson MD FAAD,c Maria Jose Rueda MD,d Hilary Baldwin MD,e Edward L. Lain MD,f Megan Landis MD,g Marta Rendon MD,8 Emil Tanghetti MD,9 and Jonathan Weiss MD10|INTRODUCTION: Acne treatment guidelines suggest a combination approach with topical therapy including a topical retinoid, benzoyl peroxide and an oral antibiotic, or oral isotretinoin (OI), as first-line treatment options for severe acne vulgaris (AV). This study evaluated the efficacy and safety of a daily regimen of 0.3% adapalene and 2.5% benzoyl peroxide (0.3% A/BPO) gel and oral doxycycline 100 mg twice daily in severe (nonnodulocystic, non-conglobate) inflammatory AV. METHODS: This was a phase 4, 12-week, single-arm, openlabel, multi-center investigational study. Subjects (males and females, 12 or older, with severe inflammatory AV, Investigator Global Assessment [IGA] 4, and less than equal to 4 nodulocystic lesions, n=186) were considered OI candidates at baseline by the investigator. OI candidacy was re-evaluated at each study visit. Efficacy endpoints included inflammatory lesion (IL) reduction (week 12), IGA success (defined as IGA 0 [Clear] or 1 [Almost Clear], weeks 4, 8, and 12), percent reduction in lesions (weeks 4, 8, and 12), and subject questionnaires (week 12). Safety assessments included adverse events (AEs) and tolerability. RESULTS: Mean IL counts were significantly reduced from baseline to the end of the study (mean [SD]; baseline, 44.8 (21.73); week 12, 14.8 (16.11); mean percent reduction, 66.2% [30.47]; P less than .0001). By week 12, 37.1% of subjects achieved IGA Success (n=69, P less than .0001). Most subjects self-reported at least moderate improvement in AV (90.2%), and were “Satisfied” or “Very Satisfied” with the study treatment overall (83.2%). 41.9% of the subjects were no longer considered by their investigator to be OI candidates at week 4. At 12 weeks, only 19.9% were still considered OI candidates. CONCLUSION: 0.3% A/BPO + DOX is an effective and safe treatment option for severe inflammatory AV, before starting OI treatment, or as an alternative when OI cannot be used. ClinicalTrials.gov identifier: NCT02899000
J Drugs Dermatol. 2018;17(3):264-273.
Garrett T. Prince BS,a Michael C. Cameron MD,a Ramin Fathi MD,b Theodore Alkousakis MDa|INTRODUCTION: 5-fluorouracil has proven to be an effective therapy in the treatment of a variety of dermatologic conditions. Approved by the United States Food and Drug Administration for the topical treatment of actinic keratoses and superficial basal cell carcinoma, 5-fluorouracil has also demonstrated efficacy in the treatment of a variety of other dermatologic diseases. While best known for its use as a topical medication, 5-fluorouracil can also be delivered intralesionally for the treatment of dermatologic disease. Recently, laser-assisted modalities for increased delivery of 5-fluorouracil have also been described METHODS: A search of the MEDLINE standard computer database, MEDLINE advanced database, and EMBASE database was conducted. RESULTS: 38 articles met criteria for inclusion in this review. These articles represented 14 randomized controlled trials and 24 case series. Each article was reviewed and summarized. The main limitation of this review is the limited number of large randomized controlled trials, as well as the non-uniformity in treatment regimens between studies. DISCUSSION: Intralesional and laser-assisted 5-fluorouracil are used in a variety of dermatologic disease processes with a wide range of efficacy and levels of evidence. Based on extent and level of evidence, our disease-specific systematic review found that the evidence is strongest for intralesional 5-FU use in the treatment of keloids, hypertrophic scars, and keratoacanthomas. This review serves as a comprehensive summary of intralesional and laser-assisted 5-fluorouracil use in dermatology.
J Drugs Dermatol. 2018;17(3):274-280.
Dermal Microflora Restoration With Ammonia-Oxidizing Bacteria Nitrosomonas Eutropha in the Treatment of Keratosis Pilaris: A Randomized Clinical Trial
Nicole Y. Lee MD MPH,a Omer Ibrahim MD,b Shilpi Khetarpal MD,c Mariya Gaber,d Spiros Jamas ScD,d Ioannis Gryllos PhD,d and Jeffrey S. Dover MD FRCPCe|Keratosis pilaris (KP) is a common skin finding that presents as follicular hyperkeratotic papules on the proximal extremities in patients with a propensity for atopy. Although often asymptomatic, the stippled appearance is cosmetically disturbing to patients and difficult to treat as current therapies are limited in availability and efficacy. Nitric oxide (NO) has been found to be essential in basic systemic and cutaneous physiologic function, specifically in terms of its anti-microbial and anti-inflammatory properties, which evolutionarily was maintained by ammonia-oxidizing bacteria (AOB). As modern hygiene practices have improved, there has been a gradual loss of cutaneous AOB and, therefore, the availability of an important source of human physiologic NO. We propose that restoring this dermal microflora with a purified strain of AOB, Nitrosomonas eutropha (D23), may reduce the overall cutaneous inflammatory state and, thus, be a potential therapeutic option for improving the cosmetic appearance of a skin condition such as KP which is often found in association with xerosis and atopic dermatitis. Clinical trial registry number: NCT03243617
J Drugs Dermatol. 2018;17(3):285-288.
Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the Second REVEAL Trial
Leslie Baumann MD,a David J. Goldberg MD,b Linda Stein Gold MD,c Emil A. Tanghetti MD,d Edward Lain MD,e Joely Kaufman MD,f Emily Weng ScD MBA,g David R. Berk MD,g and Gurpreet Ahluwalia PhDg|Rosacea is a chronic dermatologic condition with limited treatment options, particularly for persistent erythema. This pivotal phase 3 study evaluated oxymetazoline, an a1A-adrenoceptor agonist, for the treatment of moderate to severe persistent erythema of rosacea. Eligible patients were randomly assigned 1:1 to receive oxymetazoline cream 1.0% or vehicle applied topically to the face once daily for 29 days. The primary efficacy outcome was ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for rosacea facial redness (SSA) (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Digital image analysis of rosacea facial erythema was evaluated as a secondary efficacy outcome measure. Safety assessments included treatment-emergent adverse events (TEAEs) and dermal tolerability. Patients were followed for 28 days posttreatment to assess worsening of erythema (1-grade increase in severity from baseline on composite CEA/SSA in patients with moderate erythema at baseline; rebound effect). The study included 445 patients (mean age: 50.3 years; 78.7% female); most had moderate erythema at baseline (84.0% on CEA; 91.5% on SSA). The proportion of patients achieving the primary efficacy outcome was significantly greater with oxymetazoline versus vehicle (P=0.001). Similar results favoring oxymetazoline over vehicle were observed for the individual CEA and SSA scores (P less than 0.001 and P=0.011, respectively). Median reduction in rosacea facial erythema on day 29 as assessed by digital image analysis also favored oxymetazoline over vehicle (P less than 0.001). Safety results were similar between oxymetazoline and vehicle; discontinuations due to TEAEs were low (2.7% vs 0.5%). Following cessation of treatment, 2 (1.2%) patients in the oxymetazoline group and no patient in the vehicle group had rebound effect compared with their day 1 baseline score. Topical oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in the treatment of moderate to severe persistent facial erythema of rosacea.
J Drugs Dermatol. 2018;17(3):290-298.
Addressing Male Facial Skin Concerns: Clinical Efficacy of a Topical Skincare Treatment Product for Men
Elizabeth T. Makino BS CCRA MBA,a Lily I. Jiang PhD,b Priscilla Tan BA,a Tsing Cheng PhD,a and Rahul C. Mehta PhDa|The growing male skincare market reflects the increased interest of men in addressing facial aging concerns and maintaining a healthy youthful appearance. Because of differences in skin structure and aging as well as in lifestyle and behavior, male facial skin presents unique challenges that may result in different priorities or treatment strategies compared to female skin. A clinical study was conducted to assess clinical efficacy and tolerability of a topical skincare treatment product that was developed to address several male facial skin concerns related to skin quality, skin aging, and shaving. The treatment product provided significant improvements in all clinical efficacy parameters including overall photodamage, tactile roughness, fine line/wrinkles, and coarse lines/wrinkles. Furthermore, significant improvements in erythema as well as dryness/scaling were observed. Subject self-assessment questionnaires showed that the treatment product was highly rated in both self-perceived efficacy as well as product attributes. Use of skincare treatment products that tackle specific male facial skin concerns could further optimize skin quality and support healthy and youthful looking skin in men.
J Drugs Dermatol. 2018;17(3):301-306.
Phase 2 Randomized, Dose-Ranging Study of Oxymetazoline Cream for Treatment of Persistent Facial Erythema Associated With Rosacea
Janet DuBois MD,a Jeffrey S. Dover MD FRCPC,b Terry M. Jones MD,c Robert A. Weiss MD FAAD FACPh,d David R. Berk MD,e and Gurpreet Ahluwalia PhDe|Background: Rosacea is a chronic dermatologic condition with limited treatment options. Objective: This phase 2 study evaluated the optimal oxymetazoline dosing regimen in patients with moderate to severe persistent facial erythema of rosacea. Methods: Patients were randomly assigned to oxymetazoline cream, 0.5%, 1.0%, or 1.5%, or vehicle, administered once daily (QD) or twice daily (BID) for 28 consecutive days. The primary efficacy endpoint was the proportion of patients with ≥2-grade improvement from baseline on the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment of erythema (SSA-1) on day 28. Safety assessments included treatment-emergent adverse events and dermal tolerability. Results: A total of 356 patients were treated (mean age, 50.0 years; 80.1% female). The proportions of patients achieving the primary endpoint were significantly higher with oxymetazoline 0.5% QD (P=0.049), 1.0% QD (P=0.006), 1.5% QD (P=0.012), 1.0% BID (P=0.021), and 1.5% BID (P=0.006) versus their respective vehicles. For both QD and BID dosing, the efficacy of oxymetazoline 1.0% was greater than the 0.5% dose and comparable to the 1.5% dose. Safety and application-site tolerability were similar across groups. Limitations: Short-term treatment period. Conclusion: Oxymetazoline 1.0% QD provided the optimal dosing regimen and was selected for evaluation in phase 3 clinical studies. J Drugs Dermatol. 2018;17(3):308-316.
Logan W. Thomas MS4,a Ashley Elsensohn MD MPH,a Aaron Secrest MD PhD,b Terese Bergheim MD,a Jessica Shiu MD PhD,a Anand Ganesan MD PhDa|IMPORTANCE: Intramuscular (IM) steroids can be used to treat a wide variety of dermatologic diseases. Although seemingly effective and safe, this form of corticosteroid therapy may be underused amongst dermatologists. OBJECTIVE: The objective of this review is to determine the evidence regarding the efficacy and side effect profile of intramuscular triamcinolone in the treatment of dermatologic disease. EVIDENCE REVIEW: A PubMed search engine was used for this study. Inclusion criteria were studies that examined human subjects, reported clinical outcomes and side effects of intramuscular steroids for the treatment of dermatologic disease, cutaneous disease where steroids remain an accepted standard of care, studies published after 1980, and English language articles. FINDINGS: A total of 62 papers were reviewed. Six papers met criteria. They looked at alopecia areata, (2) systemic lupus erythematosus (1), Behcets disease (1), and nail lichen planus (2). Collectively, the studies included 342 patients. Study types included case series (1), retrospective observational (2), randomized prospective (2), and double-blind placebo controlled (1) studies. In this systematic review, intramuscular steroids were found to have comparable efficacy and side effect profile alone or in comparison with other steroid modalities for the select number of dermatoses investigated. CONCLUSIONS AND RELEVANCE: We conclude that intramuscular steroids can be regarded as having comparable efficacy to other steroid modalities in the treatment of steroid responsive dermatoses; and also appear to be safer in most instances with the exception of dysmenorrhea in females. Additional studies are greatly needed.
J Drugs Dermatol. 2018;17(3):323-329.
Clobetasol Emulsion Foam and Calcipotriene 0.005% Foam Combination Therapy for the Maintenance of Treatment Response in Patients With Moderate Plaque Psoriasis
Neal Bhatia MDa and Leon Kircik MDb|Optimizing combinations for psoriasis means asking patients to take control of their disease. It means balancing potency of steroids for the short-run to put out the fire and bring relief and maintaining the clearance for the long-run to reduce recurrence potential. Successful combinations are built on tolerability, ease of application, and the efficacy demonstrated by the synergy of the sum of the parts over being used separately.
J Drugs Dermatol. 2018;17(3):342-346.
Topical Tavaborole in the Treatment of Onychomycosis Complicated by Dermatophytoma: A Post-hoc Assessment of Phase II Subjects
Raza Aly PhD,a† Tate Winter PhD,b† Steve Hall PharmD,b Tracey Vlahovic DPMc|Dermatophytoma is a little-known, difficult to treat fungal infection that complicates onychomycosis. First described by Roberts and Evans in the late 1990’s, dermatophytoma presents as a dense concentration of fungal hyphae within or under the nail plate and is generally white or yellow/brown in color, and linear (streaks) or round (patches) in shape; primary etiologic organisms are dermatophytes. Oral antifungals have limited success in treating dermatophytoma owing to difficulties accessing and penetrating what is hypothesized to be a fungal biofilm. In this respect, dermatophytoma is generally treated with a combination therapy approach, often including both surgical and pharmacologic intervention for improved outcomes. A post-hoc assessment of Phase II tavaborole onychomycosis studies was conducted in order to assess the prevalence of dermatophytoma and outcomes in patients treated with topical tavaborole. Of the 366 subjects enrolled in the Phase II onychomycosis studies, we identified 102 cases of dermatophytoma; 21 of 86 (24.4%) subjects treated with tavaborole were able to achieve complete resolution of dermatophytoma by day 180, while no subjects on vehicle obtained resolution. Similarly, 23 of 86 subjects (26.7%) treated with tavaborole solution had complete resolution of dermatophytoma by day 360, while only 1 of 16 subjects (6.3%) on vehicle obtained resolution. Moreover, 13 of 19 subjects (68.4%) treated with tavaborole solution were able to sustain resolution, while only 6 of 19 (31.6%) had reoccurrence, of dermatophytoma during the 180-day washout period (day 360). We present 5 cases of dermatophytoma identified in Phase II trials that responded in a positive manner following treatment with tavaborole solution for onychomycosis of the great toenail. Although not representative of all subject outcomes, these findings provide insight into the use of topical tavaborole for dermatophytoma, a condition previously thought to respond only to oral or combination therapy.
J Drugs Dermatol. 2018;17(3):347-354.
Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study
James J. Leyden MD,a Vilma Sniukiene MD,b David R. Berk MD,b and Alexandre Kaoukhov MDb|BACKGROUND: There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris. METHODS: In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations. RESULTS: Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred. CONCLUSION: Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other tetracycline options, which may lead to less selective pressure on enteric Gram-negative bacteria, resulting in less disruption of commensal organisms and less potential for antibiotic resistance.
J Drugs Dermatol. 2018;17(3):333-338.
Gillian K. Weston MD,a Jette Hooper,b Bruce E. Strober MD PhDa|Dupilumab (Dupixent, Regeneron Pharmaceuticals and Sanofi Genzyme) is a novel biologic medication recently approved by the FDA for the treatment of moderate-to-severe atopic dermatitis in adults who have not achieved adequate control with topical medications. Dyshidrotic eczema is a distinct entity, often considered on the spectrum of atopic dermatitis, that primarily effects the palms and soles; it is often associated with considerable morbidity yet is frequently challenging to treat. We report two cases of recalcitrant dyshidrotic eczema treated successfully with dupilumab at standard dosing. Further studies to establish the efficacy of dupilumab in the treatment of dyshidrosis are warranted.
J Drugs Dermatol. 2018;17(3):355-356.
Liza Brown DO, Jennifer David DO, Stanley Skopit DO MSE FAOCD FAAD|Basal cell carcinoma (BCC) is a common skin malignancy comprising 80% of non-melanoma skin cancers.1 Over 2.8 million cases are estimated to be diagnosed in the United States alone each year. Advanced BCCs are comprised of BCCs that have metastasized to local or distant lymph nodes or organs, or locally invasive BCCs that are extensive and infiltrate vital structures such as eyes, nose, or brain. Advanced BCC tumors represent roughly 1-10% of BCCs today. Two severe case presentations and treatment options will be discussed in this case report series and review.
J Drugs Dermatol. 2018;17(3):358-362.
Stephanie Donaldson BS, Theresa Canavan MD, Peter G. Pavlidakey MD, Wendy C. Cantrell DNP CRNP, and Boni E. Elewski MD|Local adverse reactions to vaccination are typically mild and often quickly resolve. Vaccine adjuvants such as aluminum salts in combination with improper vaccination technique may result in severe local adverse reactions. As far as we know, there is only one prior case of frankly necrotic rapidly progressing vaccine site necrosis, which occurred in a pediatric patient.1 To our knowledge, this is the first adult case of vaccine site necrosis to be reported. The presumed etiology has been aluminum salt adjuvants and improper vaccination technique. Here we present an adult case of a severe local reaction to a vaccine resulting in necrosis of the epidermis and dermis with central ulceration. Skin appendages were also involved, with necrosis of eccrine coils and hair follicles. This necrotic ulceration was likely due to robust inflammatory response to aluminum salt subcutaneous injection. Correct vaccine placement, needle size, and needle length may reduce adverse local skin reactions.
J Drugs Dermatol. 2018;17(3):364-367.