BACKGROUND: Vismodegib, a hedgehog pathway inhibitor has been recently introduced as an oral therapy for locally advanced and metastatic basal cell carcinoma. Although treatment of patients with basal cell carcinoma with vismodegib has been associated with partial or complete clinical response, it is still unclear if it is also associated with histological cure.
PATIENTS: Two patients with 3 large and aggressive basal cell carcinomas were treated with Vismodegib for 6 months. The treatment was followed by Mohs micrographic surgery.
RESULTS: Two tumors disappeared clinically and one was reduced dramatically in its size following treatment with vismodegib. Mohs surgery in all three tumors revealed residual islands of BCC although margins were cleared at the end of surgery.
CONCLUSIONS: Neoadjuvant therapy with vismodegib for 6 months prior to Mohs surgery was effective in reducing the size of primary and recurrent aggressive basal cell carcinoma. However, residual tumor nests were found during surgery. Further larger studies are needed to evaluate the efficacy of Vismodegib as a neoadjuvant treatment prior to Mohs surgery.
J Drugs Dermatol. 2015;14(3):219-221.
Onychomycosis is an often overlooked and/or undertreated disease. This may be in part due to an under appreciation among both physicians and patients of its impact on quality of life and the potential for significant complications, from tinea corporis and cruris, to bacterial superinfection. Some health care providers are unaware of the effective low-risk treatments currently available. Changing demographic characteristics such as the relative aging of the population; the increasing prevalence of diabetes and peripheral vascular disease, and widespread iatrogenic immunosuppression; and changes in lifestyle practices such as earlier and greater participation in sports, are likely to lead to an increased prevalence of onychomycosis in both adults and children. Two topical onychomycosis treatments, efinaconazole 10% solution, and tavaborole 5% solution were recently approved by the FDA. This article reviews the state of knowledge and describes, briefly, these new treatment options.
J Drugs Dermatol. 2015;14(3):223-228.
BACKGROUND: Leflunomide (LEF) is an immune modulator used most commonly for rheumatoid arthritis (RA). The mechanisms of action of LEF also include anti-microbial effects, particularly anti-viral effects.
OBSERVATIONS: We present three patients with atopic dermatitis on azathioprine therapy who had multiple verrucae and in two molluscum contagiosum (MC) that were resistant to repeated conventional therapies.
These patients were switched to LEF, and all the patients showed complete resolution of their verrucae and MC within 2 months of starting therapy. In addition, all three patients showed equivalent to better control of their atopic dermatitis with LEF.
CONCLUSIONS: LEF has previously been reported to be a useful immune modulator for the treatment of severe atopic dermatitis. The spectrum of anti-viral effects previously seen with leflunomide did appear beneficial in these patients in clearing verrucae and MC, which had been resistant to conventional therapies while the patients were on azathioprine.
J Drugs Dermatol. 2015;14(3):230-234.
Ubiquitous electronic devices, such as smartphones and tablets, have the potential to enable a fundamental shift in the paradigm of healthcare as these devices may allow patients and health care providers (HCPs) to rapidly and remotely communicate with each other. Once fully realized, these devices may facilitate interactions between patients and HCPs. While these devices hold much promise, much work remains in assessing their viability in various diseases. A pilot study was conducted to investigate the use of a tablet-based numeric rating scale to assess improvements in a plaque psoriasis target lesion treated with clobetasol propionate 0.05% spray (CPS). Twenty-eight subjects with plaque psoriasis enrolled and were treated with CPS twice daily for 15 days. Target lesion severity (scale of 0 [no psoriasis] to 10 [very severe psoriasis]) and effectiveness scores (scale of 0 [none] to 3 [severe]) were recorded using a tablet-based system by the investigator and subjects. The tablet was also used to take photos of the target lesion to capture photographic evidence of improvement. Investigator and subject assessed target lesion severity and effectiveness scores improved during the study from baseline to day 15; in addition subjects indicated a high level of satisfaction with CPS treatment. Very few technological failures were reported and captured photographs were consistent visit to visit and of high quality. Taken together, this study supports the use of a tablet-based system to measure and track plaque psoriasis disease progression and also confirmed that CPS is an effective and safe treatment for plaque psoriasis.
J Drugs Dermatol. 2015;14(3):236-241.
Advances in the understanding of the pathogenesis of psoriasis have led to the development of biologic agents that target T cells and cytokines that play a specific role in the underlying inflammation associated with psoriasis (eg, tumor necrosis factor-α inhibitors, interleukin [IL]-12/23 inhibitors). In this review, evidence for the central role of IL-17 in the pathophysiology of psoriasis is presented, along with available clinical trial data on the selective IL-17 inhibitors in development. Three biologic agents that target IL-17 are currently in clinical development: secukinumab, ixekizumab, and brodalumab. Clinical studies to date suggest a favorable safety profile and the potential for better efficacy over the previous generation of agents, with Psoriasis Area Severity Index 75 response rates of up to 80% or greater. Fully published results of phase III studies of these agents are eagerly awaited.
J Drugs Dermatol. 2015;14(3):244-250.
Various extracts of polypodium leucotomos (PLE) applied topically or taken orally have been shown to have several beneficial antioxidant, photoprotectant, antimutagenic, and immunoregulatory effects. Modern studies have evaluated the efficacy of PLE orally as a photoprotective agent and for use in several photo-aggravated dermatologic disorders such as polymorphous light eruption, other photodermatoses, and melasma. No articles have been published evaluating the safety of PLE. We performed a PUBMED search for any randomized clinical trials related to PLE, or anapsos, a synonym. The primary safety endpoint of the review was any mention of an adverse event, side effect, or toxicity. Overall, 19 human and 6 basic science studies were included spanning over 40 years of research. Oral PLE was administered at daily doses ranging from 120 mg to 1080 mg. No adverse effects were reported in laboratory studies. In humans, side effects (gastrointestinal complaints and pruritus) were mild to moderate and found only in very small numbers of patients overall (16/1016 [2%]). This review concludes PLE is well tolerated at all doses administered and associated with a negligible risk of side effects.
J Drugs Dermatol. 2015;14(3):254-259.
As the pathophysiology of acne is complex and multifactorial, the continued influx of new basic science and clinical information requires careful analysis before drawing conclusions about what truly contributes to the development and progression of this chronic disease. Our objective is to review the latest evidence and highlight a number of important perspectives on the pathophysiology of acne. An improved understanding of acne pathogenesis should lead to more rational therapy and a better understanding of the role of P acnes opens new perspectives for the development of new treatments and management. Further research may be directed at targeting receptors, adhesion molecules, cytokines, chemokines or other pro-inflammatory targets implicated in the activation of immune detection and response (i.e., toll-like receptors [TLRs], protease-activated receptors [PARs]) that appear to contribute to the pathophysiology of acne. Therapeutic options that reduce the need for topical and/or oral antibiotic therapy for acne are welcome as bacterial resistance to antibiotics is a clinically relevant concern both in the United States and globally.
J Drugs Dermatol. 2015;14(3):263-268.
BACKGROUND: Retinol, a precursor of retinoic acid, has great potentials as a topical anti-aging molecule; however, only a handful of clinical investigations have been published to date.
OBJECTIVE: This study aimed to assess the efficacy and safety of 0.1% stabilized retinol on photodamaged skin during a one-year treatment.
METHODS: The investigation included two 52-week, double-blind, vehicle-controlled studies. In the main study, 62 subjects applied either a stabilized retinol formulation or its vehicle to the full face. A second exploratory study evaluated histological/histochemical markers in 12 subjects after 52 weeks of either retinol or vehicle use on contralateral dorsal forearms.
RESULTS: The retinol group showed significant photodamage improvement over vehicle at all timepoints during the study. After 52 weeks, retinol had improved crow’s feet fine lines by 44%, and mottled pigmentation by 84%, with over 50% of subjects showing +2 grades of improvement in many parameters. Additionally, at week 52, histochemical data confirmed the clinical results, showing increased expression of type I procollagen, hyaluronan, and Ki67 as compared to vehicle
CONCLUSION: This study confirms that a stabilized retinol (0.1%) formulation can significantly improve the signs of photoaging, and improvements in photodamage continue with prolonged use.
J Drugs Dermatol. 2015;14(3):271-276.
ATX-101 (deoxycholic acid [DCA] injection) is a proprietary formulation of pure synthetic DCA. When injected into subcutaneous fat, ATX-101 results in focal adipocytolysis, the targeted destruction of fat cells. ATX-101 is undergoing investigation as an injectable drug for contouring the submental area by reducing submental fat (SMF). The purpose of this study was to evaluate the safety and pharmacokinetics (PK) of the maximal therapeutic dose of ATX-101 (100 mg total dose). Following PK evaluation of endogenous DCA, subjects (N = 24) received subcutaneous injections of ATX-101 (2 mg/cm2, with or without 0.9% benzyl alcohol) into SMF; PK evaluation was repeated periodically over 24 hours. Endogenous DCA plasma concentrations measured prior to injection were highly variable within and between subjects. Similarly, following ATX-101 injection, DCA plasma concentrations were highly
variable, peaked rapidly, and returned to the range observed for endogenous values by 24 hours postdose. All subjects experienced at least 1 adverse event (AE). No death, serious AE, or AE-related discontinuations occurred. The majority of AEs were transient, associated with the area treated, and of mild or moderate severity. No clinically significant changes were reported for laboratory test results, vital signs, or Holter electrocardiograms postdosing. These data support the favorable safety and efficacy observations of ATX-101 as an injectable drug to reduce SMF.
J Drugs Dermatol. 2015;14(3):279-284.
In this evaluator-blind, placebo-controlled study, microinjections of stabilized hyaluronic acid (HA) gel for rejuvenation of aging hands were evaluated. Patients received three injections of 1.0 ml HA gel (20 mg/ml HA) in the dorsum of one hand and 1.0 ml saline in the other, over 3 months (M). Treatments were compared up to M03; comparisons with Day 1 (D01) were made up to M05 and M12 (extension study). Efficacy was evaluated by patients and investigators using the Global Aesthetic Improvement Scale (GAIS). Self-assessment questionnaires, biomechanical measurements, and adverse events (AEs) were analyzed.
Thirty women (mean age: 53 years) provided data up to M05. At M03, HA gel treatment improved hand skin condition in all patients versus D01, according to the GAIS; improvements were sustained to M12. Mean patient scores at M01–M03 were significantly higher for HA gel than for saline (P<0.05). Self-assessment questionnaire grades up to M03 were generally significantly better for HA gel versus saline (P<0.05); grades were maintained to M12. Statistically significant improvements with HA gel in hydration and elasticity was demonstrated at M03, compared with D01 and saline (P<0.05), and in terms of skin roughness versus D01. Maximum roughness (P<0.05) and waviness (P<0.01) were significantly improved versus saline.
All AEs were mild and anticipated, with no serious AEs.
Overall, HA gel injections were generally well tolerated and efficacious for rejuvenation of aging hands compared with saline. Sustained improvements at 12 months compared with baseline indicate that efficacy could be maintained long term.
J Drugs Dermatol. 2015;14(3):288-295.
The incidence of skin cancer continues to increase annually despite preventative measures. Non-melanoma skin cancer affects more than 1,000,000 people in the United States every year.1 The current preventative measures, such as sunscreens and topical antioxidants, have not shown to be effective in blocking the effects of UV radiation based on these statistics. The level of antioxidants contained in the majority of skin creams is not sufficient to majorly impact free radical damage. Sunscreens absorb only a portion of UV radiation and often are not photostable. In this review article, we present the novel use of exogenous DNA repair enzymes and describe their role in combating photocarcinogenesis and photoaging. Topical application of these enzymes serves to supplement intrinsic DNA repair mechanisms. The direct repair of DNA damage by endogenous repair enzymes lessens rates of mutagenesis and strengthens the immune response to tumor cells. However, these innate mechanisms are not 100% efficient. The use of exogenous DNA repair enzymes presents a novel way to supplement intrinsic mechanisms and improve their efficacy. Several DNA repair enzymes critical to the prevention of cutaneous malignancies have been isolated and added to topical preparations designed for skin cancer prevention. These DNA repair enzymes maximize the rate of DNA repair and provide a more efficient response to carcinogenesis.
J Drugs Dermatol. 2015;14(3):297-301.