Mark Lebwohl MD,a Andrew F. Alexis MD MPH,B Lisa A. Beck MD,c Julie K. Block BA,D Lawrence F. Eichenfield MD,E Luz Fonacier MD,f Emma Guttman-Yassky MD PhD,a Amy S. Paller MD MSc,g David Pariser MD FACP FAAD,h Jonathan I. Silverberg MD PhD MPH,i Mark Boguniewicz MD j
Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects around 13% of children and 7% of adults in the US. It can have a significant impact on the quality of life (QoL) of affected individuals due to pruritus and the visibility of lesions on the skin. AD is increasingly recognized as a systemic disease, since dysregulation of the adaptive and innate immune systems plays a key role in the underlying disease pathogenesis, which has important implications for how the condition is treated. Patients with moderate-to-severe disease who have failed to achieve disease control may benefit from systemic immunomodulatory treatments. Recently published expert perspectives outlined recommendations for the diagnosis and treatment of moderate-to-severe AD in adults, reflecting evidence-based, practical recommendations to support allergists and dermatologists in selecting appropriate treatment in the era of biologic therapies. To help clinicians understand how these practical recommendations can be implemented into clinical practice, we describe two real life case studies of adult patients with AD. In these case studies, we demonstrate how AD severity, treatment response, and treatment failure can be assessed, and the role of emerging systemic treatments in the management of moderate-to-severe AD.
J Drugs Dermatol. 2019;18(2):122-129.
William I. Roth MD, Michael Shelling MD, Keren Fishman
Background: Superficial radiation therapy (SRT) is a nonsurgical method of treating basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) lesions on the lower extremities of older individuals that might otherwise suffer complications or prolonged healing following surgical intervention.
Objective: The goal of this study was to evaluate the effectiveness of SRT for treating BCC and SCC lesions on the lower extremities of elderly patients in an outpatient clinic setting.
Methods and Materials: A retrospective review was performed using data from consecutive patients with BCC and SCC on their lower extremities and were treated with SRT.
Results: The review included patients with biopsy-proven BCC (n=38, 25%) and SCC (n=113, 75%). The mean patient age was 82.5 years and the follow-up period was ≥4 years (32%), 3 years (30%), 2 years (20%), and ≤2 years (17%). The overall success rate was over 97%. Four lesions (one BCC and three SCCs) recurred equally between genders (2 males and 2 females) with lesions >1.0 cm and all lesions were eventually cleared with other modalities.
Conclusions: Superficial radiation therapy is an effective option for eliminating BCC and SCC on lower extremities of patients who opt for nonsurgical treatment. Using SRT for BCC and SCC in elderly patients resulted in a 97.4% cure rate.
J Drugs Dermatol. 2019;18(2):130-134.
Jennifer C. Tang MD,a Larry Buckel MD,B C. William Hanke MDa
Background: Vismodegib used in the treatment of metastatic basal cell carcinoma (BCC) or locally advanced, recurrent BCC not amenable to surgery or radiation leads to various clinical changes.
Objective: Aim was to elucidate the histopathology that corresponds to tumor involution observed with vismodegib therapy.
Methods: Retrospective case series of patients treated with vismodegib between May 2012 and April 2017 with intra- or post-treatment biopsy.
Results: 42 biopsy specimens and 4 Mohs frozen sections were analyzed. Necrosis, fibrosis, and increased plasma cells were common features.
Limitations: Single center study.
Conclusion: The histologic findings of BCCs treated with vismodegib correlate with clinical response.
J Drugs Dermatol. 2019;18(2):136-138.
Zoe Diana Draelos MD,a Hemali Gunt PhD,b Stanley B. Levy MDc
Background: Rosacea is characterized by irritation associated with erythema, telangiectasias and papules/pustules. Whole formula nature-based sensitive skin products are formulated to maintain skin barrier and appropriate hydration that can lead to soothing benefits.
Objective: To evaluate the efficacy and tolerability of a regimen consisting of a cleanser containing natural oils, beeswax, and witch hazel and day and night creams containing natural oils, glycerin, and botanical anti-inflammatories (NR); and a synthetic dermatologist-recommended regimen of cetyl alcohol, sodium lauryl sulphate-containing cleanser, and glycerin, polyisobutene-containing lotion (CR) in subjects with rosacea.
Methods: 80 female subjects with rosacea who received 6 weeks of 0.75% metronidazole gel, were randomized to receive NR or CR, twice daily, for 4 weeks in conjunction with the gel. Blinded investigator global assessment of rosacea, investigator-rated, and subject-rated overall skin appearance was assessed using a 5-point scale (0=none, 4=severe) at baseline, 2 weeks, and 4 weeks. Noninvasive skin assessments for skin hydration and skin barrier function were made by corneometry and TEWL, respectively.
Results: NR resulted in improvement in investigator global assessment of rosacea measures at 4 weeks from baseline (erythema, 28%; telangiectasia, 26%; papules/pustules, 34%: P less than 0.001) and CR resulted in a 8 to 12% improvement. Differences between treatments were statistically significant. Overall skin appearance measured by the investigator was clinically and statistically improved from baseline by 32% and 12% with NR and CR, respectively. Overall skin appearance measured by subjects was improved by both NR and CR from baseline with no differences between treatments. Both regimens improved barrier function from baseline to week 4 (13%, NR; 14%, CR). NR decreased hydration by 21% from baseline at week 4 while CR increased hydration by 14% (P less than 0.001 from NR). No clinically significant tolerability issues were reported in either regimen at week 4.
Conclusion: NR was effective, well tolerated, and superior to CR in the management of rosacea, concomitantly treated with metronidazole.
National Clinical Trial Identifier: NCT03392558
J Drugs Dermatol. 2019;18(2):141-146.
Marc L. Frost MD,a Katherine Hrynewycz MD,b C. William Hanke MDc
Tumor thickness has been a key tool for prognosis of melanoma. However, with the advent of gene expression profile (GEP) assays for melanoma and the discovery of multiple melanoma subtypes, it is time to reassess how we view tumor thickness as a prognostic indicator.Herein we present ten questions for consideration by the shrewd practitioner when considering prognostic factors of melanoma.
J Drugs Dermatol. 2019;18(2):148-151.
Calvin T. Sung MS4,a,b Margit L.W. Juhasz MD,b Franchesca D. Choi RPh,a,c Natasha Atanaskova Mesinkovska MD PhDb
Introduction: Topical minoxidil is the first-line therapy for treating both male and female androgenetic alopecia. Currently there are no comprehensive reviews on the clinical efficacy of minoxidil on hair loss.
Method: A literature search was conducted to identify clinically relevant studies regarding the efficacy of topical minoxidil for human subjects for hair loss.
Results: Twenty-three pertinent studies were identified for inclusion in this review. Topical minoxidil has been studied in concentrations ranging from 0.01% to 15% for the treatment of AGA resulting in hair growth ranging from 17% to 70%. Concentrations from 3% to 5% have been used to treat alopecia areata, 2% to treat traction alopecia, and 1% to 5% for congenital hair disorders with varying levels of treatment success. Efficacy varies by ethnic groups, but topical minoxidil has been demonstrated to significantly improve quality of life even in the absence of hair regrowth.
Conclusion: Topical minoxidil is efficacious for the treatment of hair loss due to male and female androgenic alopecia, alopecia areata, with case-by-case application for traction alopecia, hair transplantation, and congenital hair disorders. Combination therapies using minoxidil with systemic, topical, and injectable therapies demonstrate increased effectiveness over monotherapies.
J Drugs Dermatol. 2019;18(2):155-160.
Azam A. Qureshi BAa and Adam J. Friedman MDb,c
Since the first reported cases in 2007, idiopathic mast cell activation syndrome has been increasingly recognized. Understanding of the cutaneous manifestations of this condition is imperative for dermatologists given the substantial clinical heterogeneity in its presentation and high estimated prevalence. A review of PubMed® and SCOPUS® databases was performed in order to investigate the most common dermatologic manifestations of idiopathic mast cell activation syndrome. Evidence to date suggests that flushing, pruritus, and clotting dysfunction or bleeding disorder are the most frequently observed dermatologic symptoms in idiopathic mast cell activation syndrome, while dermatographism has been identified as a common finding in patients as well. Mast cell activation syndromes have also been linked to connective tissue disorders, including an Ehlers-Danlos Syndrome-like phenotype possibly mediated by matrix metalloproteinases and tryptase released by mast cells. Current literature regarding dermatologic manifestations of idiopathic mast cell activation syndrome is limited by the heterogeneity of studies including clinical descriptions, inconsistency of diagnostic criteria implemented, and a paucity of literature available. This work provides a guide for dermatologists to strengthen diagnostic acuity for idiopathic mast cell activation syndrome, therefore contributing toward a goal of helping patients to receive timely, effective, and targeted therapy.
J Drugs Dermatol. 2019;18(2):162-168.
Franz R. Kerdel DO, Fabio A. Azevedo CCRC, Christina Kerdel Don PA-C MCMSc, Frank A. Don DO, Gabriella Fabbrocini MD, Francisco A. Kerdel, BSc MBBS
BACKGROUND: Treatment options are limited for patients with hidradenitis suppurativa (HS). Apremilast, an oral phosphodiesterase 4 inhibitor, may offer an attractive therapeutic option for patients with mild-to-moderate HS.
METHODS: This open-label, phase 2 clinical trial enrolled adults (≥18 years of age) with mild-to-moderate HS. Patients received apremilast 30mg twice daily for 24 weeks after a 5-day titration period. Therapy was discontinued at week 24; data were collected up to week 28. Hidradenitis Suppurativa Clinical Response 30 (HiSCR30), ie, proportion of patients with a ≥30% reduction in abscesses and nodules at week 16, was the primary endpoint. HiSCR50, ie, ≥50% reduction, was also explored. Mean changes from baseline to week 24 in the modified Sartorius, Physician’s Global Assessment, visual analog scale (VAS) for pain, and Dermatology Life Quality Index (DLQI) scores were analyzed using the Wilcoxon Rank-Sum test. Adverse events (AEs) were summarized.
RESULTS: Twenty patients (mean age, 32.5 years) were enrolled in the study. HiSCR30 was achieved in 65% of patients at weeks 16 and 24. A similar proportion of patients achieved HiSCR50. Significant mean improvements from baseline were observed for all assessments. At week 24, the overall Sartorius score improved from 35.6 to 13.9 (-21.7 change; P less than 0.001), the PGA score from 2.7 to 1.6 (-1.1 change; P less than 0.01), the VAS pain score from 27.6 to 10.9 (-16.8 change; P less than 0.05), and the DLQI score from 11.6 to 5.4 (-6.2 change; P less than 0.01). Diarrhea (20%), nausea (15%), and depression (10%) were the most commonly reported AEs. No serious AEs or deaths were reported.
CONCLUSIONS: Apremilast was safe and effective in improving HS disease activity, pain, and QoL in patients with mild-to-moderate HS. These data suggest that apremilast may have a role in the early treatment of less severe HS.
J Drugs Dermatol. 2019;18(2):170-176.
Leon H. Kircik MD,1 Hilary Baldwin MD,2,3 Edward Lain MD MBA,4 Eric Guenin PharmD PhD,5 Susan Harris MS,6 Varsha Bhatt PhD7
BACKGROUND: Acne vulgaris (acne) is a common dermatological condition typically associated with adolescents, affecting about 85% of young people. However, it is also prevalent and persistent into adulthood, particularly in females. The efficacy of tretinoin in acne is well documented with large pivotal studies. The first lotion formulation of tretinoin was developed to provide an important alternative option to treat acne patients who may be sensitive to the irritant effects of other tretinoin formulations.
OBJECTIVE: To determine whether efficacy and safety of tretinoin 0.05% lotion was similar in adolescent (less than 18 years) and adult (less than equal to18 years) women with moderate-to-severe acne.
METHODS: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled Phase 3 studies in moderate or severe acne. Female subjects (aged 9 to 58 years, N=909) randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator’s Global Severity Score [EGSS] and clear/almost clear). Safety, adverse events (AEs), and cutaneous tolerability were evaluated throughout.
RESULTS: At week 12, mean percent reduction in inflammatory and noninflammatory lesion counts in female subjects were 56.9% and 51.7%, respectively, compared with 47.1% and 34.9% with vehicle (P equals less than 0.001). Similar results were seen in adult and adolescent females in terms of reduction in inflammatory lesion counts with tretinoin 0.05% lotion; reduction in noninflammatory lesions was significantly greater in adult females (P equals 0.002). Treatment success was achieved by 23.6% of female subjects by week 12, compared with 13.5% on vehicle (P less than 0.001). Although treatment success was somewhat greater in adult females (24.6% versus 21.6%), the difference was not significant. The majority of AEs were mild and transient. There were five serious AEs (SAEs) reported (4/1, adult/adolescent, respectively). The most frequently reported treatment related AEs with tretinoin 0.05% lotion were application site pain (3.0%/5.7%), and application site dryness (4.9%/6.4%). Local cutaneous safety and tolerability assessments were generally mild-to-moderate and improved by week 12. Slight increases in mean scores were observed for scaling, burning and stinging within the first four weeks and appeared to be transient.
CONCLUSIONS: Tretinoin 0.05% lotion was significantly more effective than its vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in female acne. Noninflammatory lesion count reduction was significantly greater in adult females compared with adolescent females. The new lotion formulation was well-tolerated.
J Drugs Dermatol. 2019;18(2):178-188.
Phoebe Rich MD,a Mary Spellman MD,b Vivek Purohit MPharm PhD,c Chuanbo Zang PhD,d and Tim J. Crook MD FFPME
BACKGROUND: This study was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of tavaborole in pediatric patients.
Study Design: In this open-label, single-arm study, pediatric patients (aged 6 to less than 17 years) with distal subungual onychomycosis affecting greater than equal to 20% of the target great toenail applied tavaborole once daily to all affected toenails (2 drops/great toenail, 1 drop/other toenail) for 48 weeks. In addition, a maximal-use subgroup (aged 12 to less than 17 years) applied tavaborole to all 10 toenails and less than equal to 2 mm of surrounding skin for the first 28 days.
RESULTS: Treatment-emergent adverse events (TEAEs) were reported by 55.6% of patients; the most frequently reported (less than 5% of patients) were nasopharyngitis, contusion, sinusitis, and vomiting. Most TEAEs and local treatment reactions (LTRs) were mild or moderate and considered unrelated to treatment. There was 1 serious AE (severe appendicitis, considered unrelated to treatment) and there were no deaths, discontinuations because of AEs, or dose adjustments because of AEs. The most frequently reported LTRs were erythema and scaling. The incidence of LTRs diminished over time. Tavaborole was absorbed systemically, and plasma concentrations were measurable. The PK parameters determined in this study under maximal-use conditions indicate that steady state was achieved within the study period. For efficacy, 8.5% of patients achieved complete cure (clear nail and negative mycology [negative fungal culture and negative potassium hydroxide wet mount]) at week 52, and 14.9% achieved complete/almost complete cure at week 52 (clear or almost clear nail [less than equal to 5% dystrophic or discolored distal toenail plate] and negative mycology).
CONCLUSION: Tavaborole was well tolerated in this pediatric population, and safety, PK, and efficacy profiles were comparable with those in adults.
Trial registration: ClinicalTrials.gov identifier: NCT03405818
J Drugs Dermatol. 2019;18(2):190-195.
Caridad Rosette PhD,a Niccolette Rosette MS,a Alessandro Mazzetti MD,b Luigi Moro PhD,c Mara Gerloni PhDa
Cortexolone 17α-propionate (clascoterone) is a novel androgen antagonist that is currently being analyzed in a large phase 2 clinical trial for the topical treatment of androgenetic alopecia (AGA). While the pathogenesis of AGA is still debated, the consensus is that AGA is an androgen-dependent hair disorder with strong genetic links, and that the testosterone metabolite, dihydrotestosterone (DHT), plays a causal role in its development. DHT binds to the androgen receptor (AR) in scalp dermal papilla cells (DPC) to induce AR-mediated transcription of genes that contribute to AGA in genetically predisposed individuals.
Several studies have established that clascoterone is a potent antiandrogen that is well tolerated and has selective topical activity. The study described herein elucidates a potential mechanism of clascoterone in AGA. Clascoterone was found to inhibit AR-regulated transcription in a reporter cell line with similar efficacy to the 5α-reductase inhibitor, finasteride. More importantly, when compared with another direct AR antagonist, enzalutamide, clascoterone was significantly better at inhibiting IL-6 synthesis from DHT-stimulated primary cultures of human scalp DPC. Therefore, clascoterone may be an excellent candidate to be the first topical antiandrogen for treating AGA.
J Drugs Dermatol. 2019;18(2):197-201.
Neal Bhatia MD,a Adam Friedman MD,b and James Del Rosso DOc
The versatility of wound healing and anti-inflammatory agents can be assets to dermatologists when other therapies lack appropriate mechanisms of action, or when the risk to benefit ratio may be in question. Bensal HP ointment is a broad-spectrum antimicrobial agent with in vitro activity against important pathogens such as MRSA and gram-negative bacteria, some fungal strains, and yeasts.1 Based on the physiochemical composition of Bensal HP ointment, and its impact after application to skin, there are many potentially benefits derived from the formulation stability. While there have been several animal and human studies characterizing the antibacterial, wound healing, and anti-inflammatory properties of Bensal HP, they do not provide real world clinical experience and guidance on potential utilization in dermatology. The goal of this article is to present a variety of clinical cases for which Bensal HP was utilized as a means of translating the pre-clinical and trial data.
J Drugs Dermatol. 2019;18(2):203-206.
Raghavendra L. Girijala BS,a Imaad Siddiqi MD,B Young Kwak MD,c David Wright MD,c Dhruti B. Patel MD,d Leonard H. Goldberg MDc
BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) or drug-induced hypersensitivity (DIHS) is a rare and feared complication of frequently used medications such as anticonvulsants, sulfonamides, and allopurinol. To date, no reports of hydroxychloroquine-induced pustular DRESS syndrome have been associated with Epstein-Barr virus (EBV) reactivation nor imitated other cutaneous adverse drug reactions as in our patient.
OBSERVATION: A 56-year-old female presented with a diffuse cutaneous eruption involving the face, trunk, extremities, and palms approximately two weeks after the initiation of hydroxychloroquine therapy for a suspected Sjögren's-like process with inflammatory cervical lymphadenopathy. Skin examination demonstrated diffuse erythematous and edematous papules and pustules on her dorsal and volar hands and fingers, arms, legs, chest, abdomen, back, scalp, and face. In many areas, lesions coalesced into plaques with overlying pustules, scale, and crust. Additional notable exam findings included centralized facial edema, edema of the hands, and cervical lymphadenopathy. Laboratory workup revealed leukocytosis, peripheral eosinophilia, elevated transaminases, and a negative autoimmune workup; however, serology demonstrated EBV reactivation. Histologic assessment displayed a spongiotic dermatitis with eosinophils, superficial perivascular dermatitis, as well as corneal, subcorneal, and intraepidermal neutrophilic microabscesses, mimicking acute generalized exanthematous pustulosis or pustular psoriasis, even though clinical evaluation suggested DRESS syndrome.
CONCLUSION: To our knowledge, this is the first reported case of hydroxychloroquine-induced pustular DRESS syndrome in the context of EBV reactivation. Given hydroxychloroquine’s immunomodulatory function and association with other cutaneous manifestations, our patient represents a significant diagnostic challenge. Therefore, this case highlights the importance of knowledge regarding overlapping features, histologically and clinically, among acute generalized exanthematous pustulosis, pustular psoriasis, and DRESS syndrome.
J Drugs Dermatol. 2019;18(2):207-209.