Jamie Rosen BA,a* Angelo Landriscina BA,a* Brandon L. Adler BA,a Aimee Krauz BA,a Jessica Doerner MS,b
Mahantesh Navati PhD,c Tagai Musaev BA,a Claudia Gravekamp PhD,b Joshua Nosanchuk MD,b,d
and Adam J. Friedman MDa,c
Sanguinarine has a history of use in both folk medicine and early dermatology for the treatment of cutaneous neoplasms. Applied
indiscriminately, bloodroot is an escharotic agent with potential to cause extensive tissue necrosis. However, when used in a
controlled fashion, sanguinarine imparts selective cytotoxic/anti-proliferative activity through multiple mechanisms against human/
murine melanoma. To exploit sanguinarine’s observed activity against melanoma, a targeted delivery system is required. We present
a sol-gel based nanoparticulate platform for encapsulating sanguinarine chloride(sang-np)—a targeted therapeutic capable of
steady, reliable delivery of predictable quantities of drug over a sustained time period with minimal undesirable effects. Size and
release kinetics of sang-np were characterized using dynamic light scattering and ultraviolet-visible spectroscopy respectively. In
vitro efficacy of sang-np was assessed. At both 2 and 24 hours, free sanguinarine killed > 90% of B16 melanoma cells, assessed
via MTT assay. At 2 hours, sang-np killed a portion of melanoma cells, increasing to percentages comparable to free sanguinarine by
24 hours. Control(empty) nanoparticles exerted minimal toxicity to melanoma cells at both time points. TUNEL assay revealed that
treatment with both sanguinarine and sang-np induces apoptosis in B16 melanoma cells, suggesting that both treatments act via
the same mechanism of action. These data confirm controlled release of sanguinarine from sang-np, as well as comparable efficacy
and mechanism of action to sanguinarine alone. This suggests that nanoparticle delivery of sanguinarine may be a unique approach
to capitalize on this potent agent’s inherent anti-tumor activity and overcome many of the limitations with its current formulation.
J Drugs Dermatol. 2015;14(5):453-458.
Yang Yu BS,a,b Jackson Champer MS,a David Beynet MD,a Jenny Kim MD PhD,a,c Adam J. Friedman MDd,e
The human microbiome has recently gained prominence as a major factor in health and disease. Here we review the literature regarding
the microbiome and cancer and suggest how the microbiome may be manipulated for improved health outcomes. The gut
microbiome has been relatively well studied, and the mechanisms of how it may increase or decrease the risk of certain cancers may
apply to the skin microbiome. Additionally, the gut microbiome may directly impact the risk of cancer in the skin and other organs
by promoting systemic inflammation. The skin microbiome itself is as diverse as the gut microbiome, but research has just begun to
unravel its influence on the host. Like the gut microbiome, it affects the risk for several diseases, including cancer. By using healthpromoting
strains from the microbiome in oral or topical probiotics, it may be possible to reduce the risk of skin cancer and perhaps
even increase the likelihood of successful treatment.
J Drugs Dermatol. 2015;14(5):461-465.
Deede Y. Liu MD,a* Tarek Shaath BA,b* Anand N. Rajpara MD,a Cody Hanson BS,c
Garth Fraga MD,d Ryan Fischer MD,a and Daniel J. Aires MDa
Cutaneous T-cell lymphoma is a cancer of skin-homing T cells, of which mycosis fungoides (MF) is the most common variant.
MF treatments range from topical steroids to systemic chemotherapy. Resistant cutaneous MF nodules can present a special
challenge in that typical topical therapies may not penetrate thick lesions, and increasing systemic therapy brings added risk of
side effects. We report successful use of intralesional steroids (ILS) for treatment-resistant MF, including tumor-stage plaques
and nodules in 4 consecutive patients with focally resistant MF. ILS have been widely used to treat a broad range of cutaneous
conditions such as alopecia areata and keloids. Side effects of ILS include hypopigmentation, atrophy, telangiectasias, lilac discoloration,
acne, and striae. Rarely, and in circumstances involving unusually large doses, ILS may cause Cushing’s syndrome,
hypothalamus-pituitary-adrenal axis suppression, and reduced bone mineral density. The MF patients tolerated treatment well
without any of the above side effects other than local hypopigmention in a single patient. These results point toward further exploration
into ILS as a treatment for focally resistant MF.
J Drugs Dermatol. 2015;14(5):466-470.
Deborah S. Sarnoff MD FAAD FACPa and Robert H. Gotkin MD FACSb
We report significant changes in the appearance of the periorbital area, beyond eyelash enhancement, induced by the topical application
of bimatoprost ophthalmic solution, 0.03% (Latisse®, Allergan, Inc., Irvine, CA). To our knowledge, this is the first report
in the dermatology or plastic surgery literature describing the rejuvenating effect and overall improvement in the appearance of the
periorbital area resulting from applying Latisse to the upper eyelid margins. To date, reports in the literature discuss side-effects and
potential complications of topical bimatoprost therapy causing a constellation of findings known as PAP (prostaglandin-associated
periorbitopathy). While periorbitopathy implies pathology or a state of disease, we report changes that can be perceived as an
improvement in the overall appearance of the periorbital area. We, therefore, propose a name change from PAP to PAPS – prostaglandin-
associated periorbital syndrome. This better describes the beneficial, as well as the possible negative effects of topical
bimatoprost. Although there is a risk for periorbital disfigurement, when used bilaterally, in properly selected candidates and titrated
appropriately, bimatoprost can be beneficial. The striking improvement in the appearance of some individuals warrants further research
into the potential use of topical bimatoprost to achieve a “chemical blepharoplasty.”
J Drugs Dermatol. 2015;14(5):472-477.
Teresa M. Weber PhD,a Frank Samarin MD,b Michael J. Babcock MD,c
Alexander Filbry PhD,d and Frank Rippke MDd
INTRODUCTION: Atopic dermatitis (AD) is a chronic skin condition associated with decreased barrier function resulting in periodic
flare-ups of erythematous and pruritic lesions. Guidelines recommend daily treatment of atopic skin with emollient moisturizers
for prevention of flares and maintenance of the flare-free state. This study evaluated the efficacy of 2 steroid-free, nonprescription
eczema skin care formulations for reducing the risk of flare and relieving symptoms in infants and children with AD: Body Cream
for the daily maintenance treatment of atopic skin and Flare Treatment for the treatment of atopic flares.
METHODS: After a 2-week washout period, subjects (N=45; mean age 3.5 years) were randomized to cleanser plus daily moisturizing
with Body Cream (moisturizer group) or cleanser only (control group) for 6 months or until flare. Subjects experiencing flare received
Flare Treatment for 4 weeks.
RESULTS: The incidence of flare was significantly lower in the moisturizer group compared with the control group (21% vs 65%;
P=.006), while the median time to flare was shorter in the control group (28 vs >180 days). Risk of flare was reduced by 44.1% after
6 months of Body Cream application. Flare Treatment reduced overall eczema symptom severity at week 2 and week 4; 78.9% of
flares had improved or cleared at week 4.
CONCLUSIONS: Body Cream reduced the incidence of flare and the time to flare, reinforcing guidelines that daily emollient therapy
should be an integral part of the maintenance treatment plan for the prevention of disease flares. Body Cream and Flare Treatment
are effective over-the-counter steroid-free options for management of AD in children.
J Drugs Dermatol. 2015;14(5):478-485.
Eric P. Sorensen BSa,b and Christine Urman MDb
BACKGROUND: Botulinum toxin (BTX) and soft tissue fillers continue to gain in popularity due to their safety, affordability, quick effects,
and short recovery times. With the excellent safety profile of BTX and soft tissue fillers, patients may develop a nonchalant attitude
towards treatment with injectables. However, it is important for both patient and physician to be familiar with all the possible complications,
both common and uncommon.
OBJECTIVE: This article aims to review the rare but serious complications associated with the injectables used in cosmetic dermatology,
and the pathogenesis, diagnosis, and management of each.
METHODS AND MATERIALS: A literature review for case reports pertaining to rare adverse events following botulinum toxin or soft tissue
fillers was performed using the MEDLINE database.
RESULTS: Complications of BTX included dry eye syndrome, strabismus and diplopia, superficial temporal artery pseudoaneurysm,
neck weakness, hoarseness, and dysphagia. Complications associated with soft tissue fillers included tissue necrosis, inflammatory
nodules, hypersensitivity reaction, and blindness and cerebral ischemia.
CONCLUSION: The injector should be comfortable in diagnosing and managing the above complications, and the patient should be counseled
about these potentially harmful adverse events prior to injection.
J Drugs Dermatol. 2015;14(5):486-491.
Shari R. Lipner MD PhD and Richard K. Scher MD FACP
Onychomycosis is a common nail infection that often co-exists with tinea pedis. Surveys have suggested the diseases co-exist in
at least one third of patients, although actual numbers may be a lot higher due to significant under-reporting. The importance of
evaluating and treating both diseases is being increasingly recognized, however, data on improved outcomes, and the potential
to minimize re-infection are limited. We review a recent post hoc analysis of two large studies treating mild to moderate onychomycosis
with efinaconazole topical solution, 10%, demonstrating that complete cure rates of onychomycosis are significantly
improved when any co-existing tinea pedis is also treated.
J Drugs Dermatol. 2015;14(5):492-494.
Shivani S. Patel BS,a Karen E. Huang MS,a Alan B. Fleischer Jr. MD,a and Steven R. Feldman MD PhDa,b,c
BACKGROUND: There is a reported global decrease in the number of clinical trials conducted in recent years. We aimed to determine if
this declining trend can be extrapolated to dermatologic clinical trials.
METHODS: We conducted a query of ClinicalTrials.gov for dermatologic clinical trials from 2009 to 2013 for 6 common skin conditions:
acne, psoriasis, rosacea, eczema and atopic dermatitis, actinic keratosis, and skin cancer. Results were sorted by condition and number
of study subjects. This study did not involve any participants apart from the researchers.
RESULTS: Although there is an increasing trend in the number of trials performed annually, the results were not significant (P=.08).
The average number of patients per study has not significantly changed (P=.12), but there was a significant increase in the number
of large studies (201+ subjects) conducted over time (P=.002). Although there was significant variation based on dermatologic condition
studied (global statistic P=.01), only skin cancer demonstrated a significant change in the number of studies registered annually
(β=10.6 studies/year, P=.04).
CONCLUSIONS AND RELEVANCE: The sky does not appear to be falling, at least not yet, with regard to continued development of treatments
for patients with skin disease.
J Drugs Dermatol. 2015;14(5):497-500.