Kourosh Beroukhim BS,a Melissa J. Danesh BS,b Catherine Nguyen BS,c Annemieke Austin MD,b John Koo MD,b and Ethan Levin MDb
BACKGROUND: Monoclonal antibodies that target both Interleukin (IL)-12 and IL-23 have shown great efficacy in the treatment of psoriasis.
Recent evidence suggests that IL-23 serves a more critical role than IL-12 in the pathogenesis of psoriasis, leading to the development
of monoclonal antibodies that specifically target IL-23.
METHODS: We reviewed the results of the phase II clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab, in order to assess
the efficacy and safety profile of each agent.
RESULTS: By week 16, the proportion of patients achieving Physician Global Assessment (PGA) score of clear (0) or minimal (1) and Psoriasis Area and Severity Index (PASI 75) was above 70% among the most efficacious dosage of each agent (P< 0.001 compared to placebo for all agents). The safety profiles of the agents were similar, with the most frequently reported adverse events of nasopharyngitis,
upper respiratory infections, cough, and headache.
CONCLUSION: The anti-IL-23 agents demonstrated a rapid clinical improvement and favorable short-term safety profile. The results of the phase II trials support IL-23 as an essential target in psoriasis treatment.
J Drugs Dermatol. 2015;14(10):1093-1096.
Jennifer Gall Powell MD,a,c Raminder K. Grover MD,a,b Richard W. Plunkett PhD,a,b
Kristina Seiffert-Sinha MD,a and Animesh A. Sinha MDa
IMPORTANCE: Paraneoplastic pemphigus (PNP) is routinely diagnosed by the presence of autoantibodies for desmoplakin by indirect immunofluorescence (IIF) on rat bladder epithelium (RBE). IIF on RBE has recently been found to be positive in select cases of other blistering disorders. A new ELISA that detects envoplakin autoantibodies has recently been developed for the diagnosis of PNP. In this study, we measure the specificity of IIF on RBE and compare it to the new ELISA.
OBSERVATIONS: We measured the specificity of IIF on RBE to be 86% which is on the lower end of the previously reported specificity of 83% to 98.9%. The ELISA for envoplakin autoantibodies has a technical sensitivity of 100%, diagnostic sensitivity of 83%, and specificity of 91%.
CONCLUSIONS AND RELEVANCE: This ELISA for envoplakin autoantibodies is now commercially available and technically easier to perform then the immunoblot. We recommend that this new ELISA serves as a confirmatory test in cases of a positive IIF on RBE given its higher specificity.
J Drugs Dermatol. 2015;14(10):1103-1106.
Dedee F. Murrell MD FRCP,a Kurt Gebauer MD,b Lynda Spelman MBBS FACD,c and Lee T. Zane MDd
BACKGROUND: A novel approach for treating atopic dermatitis (AD) is the inhibition of phosphodiesterase 4 (PDE4), an enzyme involved in the proinflammatory cascade. Crisaborole topical ointment, 2% is a novel, boron-based small-molecule PDE4 inhibitor with anti-inflammatory properties. The objective of this proof-of-concept study was to assess the efficacy and safety of crisaborole topical ointment,
2% in adults with mild to moderate AD.
METHODS: This phase 2a, randomized, double-blind, bilateral, 6-week study of crisaborole topical ointment, 2% was conducted in adult patients with mild to moderate AD with 2 comparable target AD lesions. Patients were randomly assigned to twice-daily application of crisaborole topical ointment, 2% or vehicle, each to 1 of the 2 target lesions. The primary efficacy endpoint was change from baseline in Atopic Dermatitis Severity Index (ADSI) score at day 28. Safety assessments included local tolerability and incidence of adverse events (AEs).
RESULTS: A total of 25 enrolled patients received study medication. At day 28, 17 patients (68%) experienced a greater decrease in ADSI score in the active-treated lesion than in the vehicle-treated lesion; 5 patients (20%) had a greater decrease in ADSI score in the vehicle-treated lesion than in the active-treated lesion. Local application-site reactions were reported in 3 patients (12%). A total of 29 AEs were reported in 11 patients; most (90%) were mild in intensity and unrelated to study medication. No serious or severe AEs were reported, and no patient discontinued due to an AE.
CONCLUSIONS: These findings provide preliminary evidence of the efficacy and safety of treatment with crisaborole topical ointment, 2% in adults with mild to moderate AD.
The study is registered on ClinicalTrials.gov (identifier NCT01301508).
J Drugs Dermatol. 2015;14(10):1108-1112.
Leon H. Kircik MDa and Panagiotis Zografos MScb
Psoriasis is a chronic inflammatory skin disease where the use of topical corticosteroids is a mainstream treatment. However, the continuous use of high potency topical corticosteroids is limited by a variety of well known adverse events which include, atrophy, and telangiectasia. Also, inhibition of lipid synthesis by steroids can cause impairment of the epidermal barrier, which is already disrupted in most of the inflammatory cutaneous disorders such as psoriasis. This will further lead to increase transepidermal water loss (TEWL), decreased hydration, dry skin, and irritation. On the other hand, topical vitamin D analogs directly affect keratinocyte proliferation and differentiation as well as modulation of epidermal lipids and antimicrobial peptides. Although the exact mechanism of action of topical vitamin D analogs is not well understood in the treatment of psoriasis, their efficacy and safety has been shown in several clinical trials over the years and they are widely used for psoriasis. Therefore, combination of topical steroids and vitamin D analogs may be a logical option for the treatment of psoriasis.
J Drugs Dermatol. 2015;14(10):1113-1116.
J. Mark Jackson MD FAAD,a Andrew Alexis FAAD MPH FAAD,b Brian Berman MD PhD FAAD,c Diane S. Berson MD FAAD,d Susan Taylor MD FAAD,e Jonathan S. Weiss MD FAADf
Seborrheic keratosis (SK) is among the most common cutaneous lesions, affecting some 83 million Americans. Biologically benign, SK lesions do not require removal for medical reasons unless histologic confirmation of the clinical diagnosis is required or the lesions are traumatized and/or become symptomatic. These macular or popular pigmented lesions are often of cosmetic concern to patients. In addition, their natural history of gradually increasing in size, thickness, and/or pigmentation often serves as the impetus compelling patients
to present to a dermatologist for evaluation and skin cancer screening; SK is diagnosed and managed primarily by dermatologists. Data regarding SK prevalence and management from a survey of 594 practicing, board-certified dermatologists are summarized herein: Dermatologists report they diagnose an average of 155 patients per month with SK. Among SK patients presenting to dermatologists, 33% have more than 15 SK lesions and 67% have 15 or fewer SK lesions. On average, dermatologists treat 43% of their SK patients to remove lesions. Cryosurgery is the most common removal method. Other commonly employed removal methods include shave excision, electrodessication, curettage or a combination of these. While these procedures can be used to remove SK lesions effectively, each has potential drawbacks and careful patient selection is required to optimize cosmetic results particularly in skin of color patients and patients with thick or numerous lesions. While there is great interest from both patients and providers in a topical non-invasive treatment for SK, no effective topical therapeutic agent has been developed, and this remains an area of unmet need.
J Drugs Dermatol. 2015;14(10):1119-1125.
BACKGROUND: Mohs micrographic surgery (MMS) is the most useful surgical method for the treatment of skin cancer. One of the key factors in MMS is the mapping of the excised tissue in relation to its original location. Since the introduction of MMS, mapping has been modified from simple drawing to digital photographic maps.
METHOD: Maps during MMS were taken using Samsung and LG tablets. The maps were saved to the cloud in the operating rooms. A short time after, the maps were downloaded to the laboratory’s computer by the Mohs technician and processed to a digital photographic map. When additional stage was needed, the map was uploaded by the technician to the cloud and viewed by the Mohs surgeon on the tablet in the operating room.
CONCLUSION: Mohs mapping on the cloud is a new method of mapping tissue in MMS. It is an easy, fast, and accurate method of mapping and serves the new era of modern web and photographic technologies.
J Drugs Dermatol. 2015;14(10):1127-1130.
Eric Lee MD, Mina Zarei MD, Charlotte LaSenna BS, Gabriel Villada MD, and Paolo Romanelli MD
INTRODUCTION: Psoriasis is a chronic, inflammatory autoimmune disease that affects about 3% of the general population in the United States with 17% suffering from moderate to severe psoriasis. The disease process is believed to be mediated by tumor necrosis factor (TNF)-α and cytokines secreted by specialized T-cell populations including Interleukin (IL)-17, IL-22, and Interferon (IFN) γ. IL-17 plays an important role in psoriasis. In this study we evaluated the expression of IL-17A in variants of psoriasis including plaque, palmoplantar, scalp, pustular, and guttate subtypes via immunohistochemistry (IHC).
METHODS AND MATERIALS: A search of the University of Miami Dermatopathology database was performed to identify all available patient
specimens within the various subtypes of psoriasis. IL-17A IHC staining was performed using 4 μm paraffin skin sections. 1:25 dilution of IL-17A antibody was used. Stained slides were analyzed using a semi-quantitative scoring method ranging from negative to three plus.
RESULTS: Palmoplantar and pustular psoriasis cases showed consistently strong IL-17A staining. Plaque psoriasis cases showed intermittent
to strong IL-17A staining. The results in the scalp and guttate psoriasis cases showed variable results.
CONCLUSION: The results of our study suggests the significant role of the cytokine IL-17A in the development of palmoplantar and pustular
psoriasis. However, scalp and guttate subtypes showed variable expression from negative to strongly positive, which demonstrates a case by case basis expression of IL-17A. Therefore, exploring the IHC characterization of subtypes of psoriasis will help dermatologists better understand the pathogenesis of each subtype and help clinicians optimize treatments.
J Drugs Dermatol. 2015;14(10):1133-1136.
Linda F. Stein Gold MD,a Tracey Vlahovic DPM,b Amit Verma DrPH,c Babajide Olayinka MSc,c
Alan B. Fleischer Jr. MDc
BACKGROUND: Naftifine hydrochloride (naftifine) is a topical antifungal of the allylamine class, displaying fungicidal and fungistatic activity. Naftifine is generally used to treat interdigital tinea pedis; however, systemic therapy is often prescribed by healthcare providers for moccasin tinea pedis. Well-controlled clinical data on topical antifungal therapy for moccasin tinea pedis is limited.
OBJECTIVE: The objective of this analysis is to present data from two pooled randomized, vehicle-controlled studies that evaluated efficacy of once daily topical naftifine gel 2% and vehicle at end of treatment (week 2) and at 4 weeks post-treatment in subjects with moccasin tinea pedis.
METHODS: At visit 1, subjects were randomized to naftifine gel 2% or vehicle groups and subjects underwent baseline mycology culture, KOH, and symptom (erythema, scaling, and pruritus) severity grading. Naftifine gel 2% and vehicle treatment were applied once daily for 2 weeks and the subjects returned at weeks 2 and 6 for efficacy evaluation (mycology culture and grading of symptom severity). A total of 1174 subjects were enrolled with interdigital tinea pedis with or without moccasin infection. Of these subjects, 674 subjects had interdigital presentation while 500 subjects had moccasin infection in addition to the interdigital presentation. All 1174 subjects with interdigital presentation satisfied the inclusion criteria of a minimum of moderate erythema and scaling, and mild pruritus. Of the 500 subjects who had moccasin presentation, 380 satisfied the same inclusion criteria as mentioned above. Since data was analyzed as observed cases, between 337 and 349 subjects had data available for analysis of efficacy. Mycologic cure is defined as a negative dermatophyte culture and KOH, treatment effectiveness is defined as mycologic cure and symptom severity scores of 0 or 1, and complete cure is defined as mycologic cure and symptoms severity scores of 0.
RESULTS: At week 6, the cure rates in the naftifine arm vs. the vehicle were statistically higher (P<0.0001) for mycological cure rate (65.8% vs. 7.8%), treatment effectiveness (51.4% vs 4.4%), and complete cure rate (19.2% vs 0.9%).
CONCLUSION: Two weeks application of topical naftifine gel 2% is an effective monotherapy treatment for moccasin tinea pedis.
J Drugs Dermatol. 2015;14(10):1138-1144.