Ryan M. Trowbridgea and Mark R. Pittelkow MDb
Epigenetic phenomena, including DNA methylation, histone modification, and genetic regulation by miRNAs, are potentially heritable
genetic regulatory changes that are not attributed to direct alterations in the DNA sequence of base pairs. They may explain
the link between psoriasis risk alleles and disease development, as alleles possess various potentials to undergo epigenetic modification.
Multiple genes involved in psoriasis pathogenesis demonstrate abnormal methylation patterns including those involved in
epidermal differentiation and proliferation, immunity, the cell cycle, apoptosis, inflammation, and IFN-γ and TNF-α signaling. Hypoacetylation
of histone H4 is observed in peripheral blood mononuclear cells of psoriatic patients, and the degree of hypoacetylation
of histone H4 is inversely correlated to the PASI score. Investigators have reported both increased and decreased expression of
miRNAs in patients with psoriasis, and have described and speculated a number of possible mechanisms for their roles in pathogenesis.
Interestingly, the altered methylation patterns observed in psoriasis appear to be normalized by treatment with biologics
directed at TNF-α inhibition. However, attempts to directly correlate epigenetic regulatory mechanisms with expression of genes
observed in psoriasis have been limited thus far, and correlating miRNA expression levels to disease phenotypes can be challenging
and inconsistent. Hopefully, the goal of drawing clinically relevant conclusions about the role of epigenetics in psoriasis will be
aided by recent methods that enable fast and sensitive epigenomic profiling. Drugs targeting epigenetic mechanisms are currently
being explored, though not for psoriasis, but specificity to pathogenetic mechanisms remains elusive. However, the amenability of
cutaneous disease to topical therapies may elevate their usefulness in the treatment of this common skin disorder.
J Drugs Dermatol. 2014;13(2):111-118.
Jason Chouake MD,a Aimee Krausz BA,b Brandon L. Adler BA,b Hillel W. Cohen PhD MPH,c
Joshua D. Nosanchuk MD,d,e and Adam Friedman MDb,f
IMPORTANCE: There is currently no data detailing the degree to which dermatologists follow CDC/Infectious Diseases Society of America
(IDSA) guidelines in the treatment of abscesses, which recommend that incision and drainage (I+D) as primary therapy for skin and
soft tissue infections (SSTI).
OBJECTIVE: To evaluate the management of skin abscesses by dermatologists.
DESIGN, SETTING, PARTICIPANTS: A national email survey of 780 dermatologists was conducted from May-June 2012. Awareness, experience,
and preparedness of respondents for abscess treatment, as well as the treatment practices in different clinical scenarios were
evaluated. Response rate = 65% (n=510). Eligibility criteria: board certified/eligible dermatologists practicing in US. Main practice affiliation:
solo (20%), group (33%), university health system/academic (32%), multi-specialty (13%), and other (2%). Main practice setting:
urban (49%), suburban (42%), and rural (9%).
MAIN OUTCOME and MEASURES: Practitioner report of: awareness of national guidelines, use of I+D in initial management of uncomplicated
abscess found on face, trunk, and extremity on patients age 6 months, 3, 15, 50, and 80 years, and use of antibiotics in the
RESULTS: 99% of respondents were capable of performing I+D in their practice. The IDSA recommends cultures in all patients treated with
antibiotic therapy, and does not recommend antibiotics for the treatment of simple abscess. 18% of respondents reported culturing abscesses
less than 50% of the time, while 91% incorporated antibiotics into initial treatment. Nearly a quarter (24%) of respondents would
choose an initial antibiotic that would not cover Methicillin-resistant Staphylococcus aureus (MRSA). For facial abscesses, as the age of
the patient increased from infant, respondents were more likely to incorporate I+D into their initial treatment. For abscesses on the trunk
and extremities, respondents were less likely to I+D infants and toddlers, compared to adolescents, adults and the elderly.
CONCLUSION: Although most dermatologists were prepared to manage uncomplicated abscesses (98%), this survey identifies gaps in
clinical standards of care established by the CDC/IDSA. Identification of these practice gaps may impact physician practice and dermatology
residency curricula, and may serve to improve abscess management and antibacterial stewardship in the outpatient setting.
J Drugs Dermatol. 2014;13(2):119-124.
Erin Lessner MD,a Samantha Fisher MD,b Katherina Kobraei MD,b Michael Osleber MD,b Rebecca Lessner BS,c Lauren Elliott MD,d and Stanton Wesson MDb
PURPOSE: To access the efficacy of spironolactone and topical retinoids in the treatment of female cyclical acne.
METHODS: A retrospective chart review on 41 female patients age 19-57 years old with cyclical acne was performed. Patients were examined
over the course of 2 to 102 months while taking 50 to 200mg of spironolactone and topical tretinoin 0.025% or adapalene 0.1%
cream. All were diagnosed with acne rated mild to severe, prior to treatment, and were started on an initial dose of 50mg po daily. If
significant improvement was not seen within the first 3-6 months, the dose was either held or increased in 25mg increments every 3
months. Patients on oral and topical antibiotics, as well as patients on photodynamic therapy were excluded from the study. The response
to treatment was rated on a 0-4 scale with 0 being no response and 4 corresponding to clear skin.
RESULTS: One patient (2.4%) had no response to treatment. This patient was only on 50mg po daily for only 2 months. Only 5 (12.2%)
patients had minimal response to treatment and 9 (22.0%), 12 (29.3%), and 14 (34.1%) had a good, excellent, or clear response respectively.
The study showed 26 (63.4%) women on treatment with spironolactone and topical retinoids had an excellent or clear outcome,
and 35 (85.4%) were considered to have a good, excellent, or clear response.
CONCLUSION: The addition of spironolactone to topical retinoid treatment suggests a superior response to retinoids alone in clearance
of female adult cyclical acne.
J Drugs Dermatol. 2014;13(2):126-129.
Adam J. Luber BA, Shaheen H. Ensanyat BS, and Joshua A. Zeichner MD
The human circadian clock ensures that biochemical and physiological processes occur at the optimal time of day. In addition to a
central pacemaker in the body, recent evidence suggests that peripheral mammalian tissues also possess autonomous circadian oscillators,
which are regulated by genes linked to distinct tissue-specific functions. The skin is situated in a position naturally exposed
to diurnal environmental changes. The skin's chronobiological functioning influences skin aging, cell repair and development of skin
cancers, as well as optimal timing of drug delivery to the skin. An understanding of circadian skin-related functions and the impact
of their disruption allow clinicians to improve therapeutic decision-making and maximize the effectiveness of prescribed treatments.
J Drugs Dermatol. 2014;13(2):130-134.
Laura F. Sandoval DO,a Ashley Semble MS,a Cheryl J. Gustafson MD,a Karen E. Huang MS,a Michelle M. Levender MD,a and Steven R. Feldman MD PhDa,b,c
BACKGROUND: The treatment of acne can be difficult, with suboptimal adherence resulting in poor treatment outcomes.
PURPOSE: To determine whether demonstrating to patients how to properly apply a topical acne medication through the use of a sample
product will improve adherence.
METHODS: Subjects with mild to moderate acne were instructed to use adapalene/benzoyl peroxide gel once daily for six weeks. Subjects were
randomized into sample or no sample group. Sample group received a demonstration on how to apply the medication using a product sample.
The primary outcome was median adherence, recorded using electronic monitoring, and secondary outcomes were efficacy measures including
the Acne Global Assessment (AGA) and lesion counts and the Perceived Medical Condition Self-Management Scale (PMCSMS).
RESULTS: Data from 17 patients was collected and analyzed. Median adherence rates were 50% in the sample group and 35% in the
no sample group (p=0.67). The median percent improvement in non-inflammatory lesions were 46% for the sample group and 33%
for the no-sample group (p=0.10).
LIMITATIONS: The small size of this pilot study limited the extent of subgroup analyses.
CONCLUSIONS: Objective electronic monitoring expanded our previous observations of poor adherence in the treatment of acne. There
is a considerable potential effect size on adherence for the use of samples, supporting the need for future, well powered studies to
assess the value of using samples in the treatment of acne and other dermatologic skin diseases.
J Drugs Dermatol. 2014;13(2):135-140.
Daniela Monti PhD,a Silvia Tampucci PhD,a Patrizia Chetoni PhD,a Susi Burgalassi PhD,a and Federico Mailland MDb
One of the pre-requisite for a successful topical antifungal drug indicated for onychomycosis is its bioavailability into the nail unit for
achieving fungal eradication and clinical benefit. The aim of this study was to compare in vitro permeation/penetration through and into
human nails of amorolfine (MRF) from a 5% anhydrous commercial formulation (Loceryl®) and ciclopirox (CPX) from the 8% aqueous
formulation in hydroxypropyl chitosan (HPCH) technology (Onytec®). The ability of the active ingredient to reach efficacious concentrations
to inhibit nail pathogens was also evaluated. The amounts of drug permeated and retained in human healthy nails were determined
using a suitably modified diffusion apparatus. HPLC analysis of the samples was performed. The HPCH-based CPX formulation
demonstrated an efficient penetration into and permeation through the nail plates. Conversely, Loceryl® produced an amount of MRF
permeated through and penetrated into the human toenails significantly lower than CPX. The evaluation of the efficacy index showed
a higher potential efficacy of Onytec® with respect to Loceryl® on nail pathogens. The present work not only reinforced the previous
results on different experimental substrates, but pointed out the superiority of HPCH-based Onytec® formulation containing CPX with
respect to Loceryl® commercial product with MRF, both in terms of higher permeation through and penetration into the human nail,
and for the efficacy towards the most common ungual pathogens.
J Drugs Dermatol. 2014;13(2):143-147.
Samreen Z. Choudhry MD,a Neal Bhatia MD,b Roger Ceilley MD,c Firas Hougeir MD,d
Robert Lieberman MD,e Iltefat Hamzavi MD,a and Henry W. Lim MDa
Polypodium leucotomos extract (PLE), derived from the tropical fern of Polypodiaceae family, has properties ranging from immunomodulatory
and antioxidative to photoprotective. It is these multiple mechanisms of action, in combination with a favorable side effect
profile, which makes PLE a promising adjunctive treatment for several dermatologic disorders. Studies are summarized on the use
and potential applications of PLE in the treatment or management of photodermatoses, vitiligo, melasma, psoriasis, atopic dermatitis,
and more recently, in minimizing infections in high-performance athletes. More data, however, with larger sample sizes are needed to
confirm these benefits.
J Drugs Dermatol. 2014;13(2):148-153.
Brian Berman MD PhD,a Gary Goldenberg MD,b C. William Hanke MD,c Stephen K. Tyring MD PhD,d Wm Philip Werschler MD,e Kim Mark Knudsen PhD,f Joana Goncalves MD,g Thomas Larsson Dr Med Sci,h Torsten Skov MD PhD,i and Neil Swanson MDj
INTRODUCTION: Cryosurgery is the most common treatment for actinic keratosis (AK) in the United States. Efficacy with cryosurgery is
variable, and is a modality for treating individual, visible lesions while failing to treat subclinical lesions.
METHODS: FIELD Study 1 (NCT01541553) is a phase 3, multicenter, randomized, double-blind study that evaluated the short- (11-week)
and long- (12-month) term efficacy and safety of sequential AK treatment using cryosurgery with liquid nitrogen followed by ingenol
mebutate gel, versus cryosurgery followed by vehicle.
RESULTS: Overall, 329 patients were randomized to ingenol mebutate 0.015% gel (n=167) or vehicle (n=162) 3 weeks after cryosurgery.
Baseline characteristics were balanced across groups. At week 11, complete clearance rate (100%) in the treatment area was higher
for ingenol mebutate gel compared with vehicle (60.5% vs 49.4%, respectively; P=.04). Mean percentage reduction in number of AKs
versus baseline was also numerically higher for ingenol mebutate gel (82.7% vs 75.6%). A general reduction from baseline lesion count
was observed 3 weeks after cryosurgery. Treatment after cryosurgery was well tolerated.
CONCLUSIONS: Short-term (11-week) AK clearance rates on the face or scalp with ingenol mebutate gel after cryosurgery were higher
than with cryosurgery alone.
J Drugs Dermatol. 2014;13(2):154-160.
Leon Kircik MDa,b,c and Neh Onumah MDd
The treatment of tinea pedis with hyperkeratosis has always been challenging due to presence of thick scales even after the resolution of
active fungal infection. Patients usually identify hyperkeratosis with active disease. Therefore, a regimen of an antifungal and a keratolytic
agent would be useful not only clearing the skin clinically but also addressing patients’ perceptions.
J Drugs Dermatol. 2014;13(2):162-165.
Neil Swanson MD,a Christina Cognata Smith PharmD,b Mandeep Kaur MD,b and Gary Goldenberg MDc
BACKGROUND: Imiquimod 3.75% and 2.5% creams were studied for the treatment of actinic keratosis (AK) of the full face or balding
scalp, to determine comparable efficacy and tolerability to imiquimod 5% cream.
METHODS: In two identical multicenter, randomized, double-blind, placebo controlled studies. Adult subjects with 5 to 20 visible lesions,
or palpable AKs in an area that exceeded 25cm2 on either the face or balding scalp were randomized to imiquimod 3.75%, 2.5% or
vehicle cream (1:1:1) applied once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy
was assessed 8 weeks posttreatment (End of Study Visit [EOS]). Primary efficacy was rate of complete clearance of AK lesions. Secondary
efficacy endpoints were rate of partial clearance at EOS (≥ 75% reduction in number of AK lesions compared to baseline) and
median percent decrease from baseline lesion count. Safety assessments included visual assessment of local skin reactions (LSRs),
number and duration of study treatment rest periods required due to intolerant LSRs, adverse events (AEs) and clinical laboratory tests.
RESULTS: Overall 479 patients were randomized to imiquimod 3.75%, 2.5%, or vehicle. Complete clearance rates were 35.6%, 30.6%,
and 6.3% respectively (both P<.001 versus vehicle). The difference in complete clearance rates (imiquimod minus vehicle) was 29.3%
and 24.3%, respectively. Partial clearance rates were 59.4%, 48.1%, and 22.6% respectively (both P<.001 versus vehicle). Median %
reductions in AK lesions were 81.8%, 71.8%, and 25.0% respectively (P<.001 versus vehicle). All primary and secondary efficacy endpoints
were greater in Study 1. Photodamage in the treatment area was 'much improved' with imiquimod 3.75%. Both active creams
were well tolerated with few treatment-related discontinuations.
CONCLUSIONS: In two well-controlled Phase 3 studies, both imiquimod 3.75% and 2.5% creams were more effective than vehicle and
well tolerated when administered daily as a 2-week on/off/on regimen to treat AK. Reduction in AK lesions was comparable to that
reported with imiquimod 5% with fewer local AEs.
J Drugs Dermatol. 2014;13(2):166-169.
Andrew F. Alexis MD MPH,a Lori A. Johnson PhD,b Nabil Kerrouche MSc,c and Valerie D. Callender MDd
Three multicenter, randomized, double blind, parallel-group, placebo controlled studies involving 3,855 subjects established the
safety and efficacy of an adapalene benzoyl peroxide topical gel in the treatment of acne for all skin types. The data from these 3
studies were pooled and the subgroup of self-identified black subjects was analyzed separately. Significantly more black subjects
had IGA success with adapalene-BPO than with vehicle at week 12. Significantly more black subjects also had decreased total, inflammatory,
and noninflammatory lesion counts with adapalene-BPO that were seen as early as week 1. Adapalene-BPO was well
tolerated in the black subjects included in this analysis and no cases of treatment-related PIH were observed. Similar results were
obtained for this subgroup as the overall population from the 3 studies. Based on the results from this analysis, adapalene-BPO is a
safe and effective treatment for acne in black skin.
J Drugs Dermatol. 2014;13(2):170-174.
Jorge Ocampo-Candiani MD,a Osvaldo T. Vázquez-Martínez MD,a José Luis Iglesias Benavides MD,b Kristin Buske MD,c Annette Lehn,d and Clemens Acker MDd
BACKGROUND: Abdominal Cesarean sections (C-sections) are frequently associated with an increased risk of excessive or unpleasant
scarring. A topical scar gel containing extract of Allium cepae, allantoin and heparin (Contractubex®; Merz Pharmaceuticals GmbH,
Germany), has shown efficacy in improving the appearance of various scar types.
OBJECTIVE: To investigate the efficacy of the topical scar gel, Contractubex, in the early treatment of C-section scars.
MATERIALS & METHODS: A total of 61 females, aged ≥18 years, who had given birth by elective C-section for the first time within the last
5–10 days, were included in this prospective, randomized, single-center study. Patients were advised to apply the topical scar gel twice daily
(treatment group), or received no treatment (control group). Efficacy was evaluated at 6 and 12 weeks after a baseline visit using the Patient
and Observer Scar Assessment Scale (POSAS), a validated scar assessment tool comprised of a Patient Scale and an Observer Scale.
RESULTS: Analysis revealed a significant change in the POSAS Patient Scale total score, with a 14.2% improvement in the treatment
group compared with a decline of similar magnitude (−14.8%) in the control group at week 6. Significant improvements were also
seen for POSAS Patient Scale sub-items in the treatment group compared with the control group for scar color (13.6% vs −18.5%,
respectively, P=0.0284), stiffness (12.5% vs −34.6%, respectively, P=0.0029), and irregularity (29.4% vs −46.2%, respectively,
P=0.0140) after 6 weeks of treatment. No significant changes were observed for the POSAS Observer Scale total score or its subitems
after treatment with the topical scar gel, although there was a strong overall trend in favor of the treatment group. No significant
adverse events were observed during the study.
CONCLUSION: Contractubex represents an efficacious and well-tolerated preventative treatment that rapidly and significantly improves
the color, stiffness and irregularity of C-section scars.
J Drugs Dermatol. 2014;13(1):176-182.
BACKGROUND: Radiofrequency-induced heating of dermal and subdermal tissue promotes skin contracture; however, the temperature
threshold for inducing an epidermal burn is lower than the therapeutic temperature thresholds required for collagen remodeling, and
therefore, there is the possibility of epidermal burn. Herein, we evaluate a radiofrequency treatment that provides novel real-time subdermal
and epidermal temperature monitoring.
METHODS: A retrospective chart review of 18 subjects undergoing thermistor-controlled subdermal skin tightening via percutaneous
radiofrequency was conducted. During the treatment, epidermal temperature was concurrently monitored by a handheld infrared laser
thermometer and a forward looking infrared camera system and peak temperatures readings were reported and evaluated.
RESULTS: Mean temperatures of 43.6 and 38.2oC were reported for the infrared camera and infrared thermometer. The Bland-Altman
plot analysis reported a bias of 5.38oC and 95% limits of agreement between 0.60 and 10.15oC. Additionally, the mean difference or
bias of 5.38oC was statistically significant (P less than 0.0001).
CONCLUSION: Our preliminary data supports a superior form of thermoregulation for the purposes of skin tightening that integrates
continuous subsurface and epidermal temperature monitoring.
J Drugs Dermatol. 2014;13(2):185-189.
Z. Paul Lorenc MD FACSa and Elizabeth Daro-Kaftan PhDb
Reversal of the visible signs of facial aging with the use of injectable products as an alternative to surgery has become more popular,
with nearly 5 million procedures performed in the United States in 2012. Volume augmentation products, such as hyaluronic acid
(HA), calcium hydroxylapatite (CaHA), and poly-L-lactic acid (PLLA), are often used in combination with one another and with neurotoxins
for facial rejuvenation because of the complementary modes of action. This article presents 2 case reports involving patientspecific
combinations of 2 different HA products, injectable PLLA, and CaHA with incobotulinumtoxinA or abobotulinumtoxinA. The
combination of HA, CaHA, PLLA, and neurotoxins has resulted in outstanding outcomes for many patients, with no clinical evidence
of increased adverse events secondary to combination therapy.
J Drugs Dermatol. 2014;13(2):191-195.