Lawrence F. Eichenfield MD,a Zoe Draelos MD,b Anne W. Lucky MD,c Adelaide A. Hebert MD,d Jeffrey Sugarman MD,e Linda Stein Gold MD,f Diane Rudisill BS,g Hong Liu MS,g and Vasant Manna MDg
OBJECTIVE: Evaluate the efficacy and safety of adapalene 0.1%-benzoyl peroxide 2.5% gel (adapalene-BPO) in patients 9-11 years old
with acne vulgaris.
METHODS: Enrolled subjects were male or female, with a score of 3 (moderate) on the Investigator’s Global Assessment (IGA) scale.
Subjects were randomized to receive adapalene-BPO or vehicle once daily for up to 12 weeks. Efficacy was evaluated by success rate
(percentage of subjects rated "clear" or "almost clear") at each visit, median percentage changes from baseline in total, inflammatory
and non-inflammatory lesion counts at each visit, the Children’s Dermatology Life Quality Index (C DLQI) at baseline and week 12, and
the Parent Assessment of Acne at week 12. Safety was assessed through evaluations of adverse events (AEs) and local tolerability
[erythema, scaling, dryness, and stinging/burning on scales ranging from 0 (none) to 3 (severe)].
RESULTS: A total of 142 subjects were randomized to adapalene-BPO and 143 to vehicle. At study endpoint (week 12), adapalene-BPO was
significantly superior to vehicle regarding treatment success (49.3% vs 15.9%, respectively), and regarding percentage reduction in total
lesion counts (68.6% vs 19.3%), inflammatory (63.2% vs 14.3%), and non-inflammatory lesion counts (70.7% vs 14.6%) (all P<.001).
More subjects using adapalene-BPO reported that their acne had no effect on their quality of life, and parents noted that their child’s acne
significantly improved. Adapalene-BPO was well tolerated, with mean tolerability scores less than 1 (mild).
CONCLUSIONS: In preadolescents with acne, adapalene-BPO leads to significantly superior treatment success and lesion count reduction
compared to vehicle.
J Drugs Dermatol. 2013;12(6):611-618.
Andrea L. Zaenglein MD,a Ava Shamban MD,b Guy Webster MD PhD,c James Del Rosso DO FAOCD,d Jeffrey S. Dover MD FRCPC,e Leonard Swinyer MD,f Linda Stein MD,g Xiaoming Lin MS RN,h Zoe Draelos MD,i Michael Gold MD,j and Diane Thiboutot MDa
BACKGROUND: Moderate to severe acne vulgaris is often treated with a combination of an oral antibiotic, topical antibiotic/retinoid, and benzoyl
peroxide (BP), but data are limited on the efficacy of this and other combination regimens that incorporate both oral and topical therapies.
METHODS: Patients were required to be aged 12–30 years with moderate to severe acne (grades 3–4 acne on the Investigator's Global
Assessment [IGA]) and deemed potential candidates for treatment with isotretinoin. Enrolled patients were given triple-combination
therapy, defined in this study as oral minocycline HCl extended release 1 mg/kg QD, 6% BP foaming cloths used QD, and clindamycin
phosphate 1.2%/tretinoin 0.025% gel applied QD, and were evaluated at baseline and weeks 2, 4, 8, and 12.
RESULTS: A total of 97 patients were enrolled in the study. At week 12, 89% of patients had at least a one-grade improvement from
baseline IGA and 96% had at least a one-grade improvement from baseline Global Aesthetic Improvement Scale score. Mean±SD in-
flammatory, non-inflammatory, and total lesion counts decreased from baseline by 61.8%±38.3%, 48.8%±34.5%, and 56.5%±29.9%,
respectively. The percentage of patients evaluated as candidates for isotretinoin by independent photographic review was 77% (69/90)
at baseline and only 16% (14/90) at week 12. Treatment-related adverse events (AEs) occurred in eight of 97 (8%) patients. Triplecombination
therapy was not associated with any serious AEs or AEs leading to discontinuation.
CONCLUSION: Triple-combination therapy was well tolerated and substantially reduced facial acne lesion counts, with 84% of patients
judged to no longer be candidates for isotretinoin therapy by study end. These data support the clinical observation that a triple-combination
regimen incorporating oral minocycline (dosed by patient weight), BP foaming cloths 6% QD, and clindamycin phosphate 1.2%/
tretinoin 0.025% gel QD can substantially improve moderate to severe acne vulgaris.
J Drugs Dermatol. 2013;12(6):619-625.
James Q. Del Rosso DO FAOCD
Oral isotretinoin is a non-aromatic oral retinoid that is highly effective for the treatment of severe inflammatory acne vulgaris that is
refractory and/or prone to scarring, and has also been used successfully to treat several other disorders in selected cases. Since its
introduction into the United States marketplace in 1982, it has been well recognized that cutaneous side effects characterized by
xerotic and desquamative changes are very common, and appear to be related to epidermal dyscohesion, and to some extent the
sebosuppressive effects of the drug. Additionally, increased susceptibility to staphylococcal colonization has also been observed.
The epidermal barrier impairments that have been associated with oral isotretinoin are reviewed in this article along with clinical
implications. Strategies to mitigate the altered effects of epidermal barrier functions are reviewed including the importance of topical
barrier repair therapy.
J Drugs Dermatol. 2013;12(6):626-631.
Ma. Beatrice Alora Palli MD,a,b Claire Marie Reyes-Habito MD,b Xinaida T. Lima MD MPH,c and Alexa B. Kimball MD MPHa,b
BACKGROUND: Acne is a common disease of the face, chest and back, initially triggered by androgens. 3mg Drospirenone (DRSP)/0.02mg
ethinyl estradiol (EE), an oral contraceptive and antiandrogen, has been effective in treatment studies of facial acne in women, but
investigations on its efficacy for truncal acne are limited.
OBJECTIVE: In this study, we sought to evaluate the safety and efficacy of 3mg DRSP/0.02mg EE versus placebo in the treatment of
truncal acne in women.
METHODS: Females, age 18-45, with 10 to 50 truncal acne lesions, were randomized in this double-blind study to 3mg DRSP/0.02mg
EE (n=15) or placebo (n=10) administered in a 24/4 regimen given for 24 weeks. Noninflammatory, inflammatory and total truncal
acne lesion counts were assessed from baseline to endpoint and mean percent change compared. Investigator Global Assessment
(IGA) and Subject Global Assessment (SGA) were assessed based on scoring scales, and the percentage of subjects rated as
success with clear (score 0) or almost clear (score 1) were computed.
RESULTS: The 3mg DRSP/0.02mg EE group had significant reductions in mean percent change in noninflammatory, inflammatory and
total lesions by 52.1%, 53.2%, and 57.3%, respectively, compared to placebo with -9.2%, 18.2% and 17.0 %, respectively, by week
24 (p = 0.02, 0.05 and 0.02, respectively). The percentage of subjects on 3mg DRSP/ 0.02mg EE rated as treatment success were
53.3% and 60% based on IGA and SGA respectively. The regimen was also well tolerated by patients.
CONCLUSIONS: 3mg DRSP/ 0.02 mg EE is a safe and significantly effective treatment for moderate truncal acne.
J Drugs Dermatol. 2013;12(6):633-637.
Hilary E. Baldwin MD,a Marge Nighland BS,b Clare Kendall MA,c David A. Mays PharmD MBA,c Rachel Grossman MD,b,c and Joan Newburger PhDc
Topical tretinoin has been approved for use in dermatology for 40 years and is currently approved for the treatment of acne vulgaris
and photodamage. During this time, topical tretinoin has accumulated significant efficacy and safety data in the treatment of acne and
photodamaged skin and demonstrated clinical potential for treating a range of other dermatologic conditions. The diverse effects may
be due to complex underlying mechanisms of action associated with tretinoin, including keratolytic activity, collagenesis, and other
mechanisms associated with the activation of nuclear retinoic acid receptors (RARα, RARβ, and RARγ). In this article, we review the
history of topical tretinoin use to date and outline emerging research suggesting that topical tretinoin may have potential clinical use
for treating a multitude of other dermatological conditions when used either as monotherapy or in combination with other agents. We
also describe newer formulations of topical tretinoin that have been designed to reduce irritation potential. In light of the substantial history
of safety and efficacy of topical tretinoin in acne and photodamage, we speculate that it holds promise in treating many additional
dermatological conditions, which may be explored in future research.
J Drugs Dermatol. 2013;12(6):638-642, e94-e105.
Gary Grove PhD,a Charles Zerweck PhD,a and Jennifer Gwazdauskas MBAb
Benzoyl peroxide (BPO) is a cornerstone of acne therapy, often used in combination with a topical antibiotic and/or a retinoid. Three
independent 2-week studies were conducted in healthy subjects to compare the tolerability and irritation potential of topical treatment
with Duac® Gel (BPO 5%–clindamycin phosphate 1.2%) vs Acanya® Gel (BPO 2.5%–clindamycin phosphate 1.2%), Aczone® Gel (dapsone
5%), or Epiduo® Gel (BPO 2.5%–adapalene 0.1%). For each study, subjects were randomized to apply one of the comparative
products on one side of the face; the contralateral side remained untreated. Primary (erythema and dryness) and secondary tolerability
assessments were performed throughout the study. Independent blinded expert grader assessments of erythema found no significant
overall difference between any of the comparative groups. Treatment with Epiduo Gel resulted in a significant increase in dryness
and evaporative water loss values compared with Duac Gel. Overall, subject self-assessments were equally favorable across all study
groups, although the Epiduo Gel group reported a higher frequency of adverse perceptions (ie mild burning/stinging). In conclusion,
the four topical acne medications tested were well tolerated throughout the study period. Treatment with Epiduo Gel resulted in a
significant increase in dryness, evaporative water loss, and sensations of burning and stinging. No other significant differences in self-assessment
perceptions were observed between treatments.
J Drugs Dermatol. 2013;12(6):644-649.
Joseph Fowler Jr. MD,a J. Mark Jackson MD,a Angela Moore MD,b Michael Jarratt MD,c Terry Jones MD,d Kappa Meadows MD,e Martin Steinhoff MD,f Diane Rudisill BSc,g and Matthew Leoni MDg on behalf of the Brimonidine Phase III Study Group
BACKGROUND: Brimonidine tartrate, a highly selective α2-adrenergic receptor agonist with potent vasoconstrictive activity, was shown
to reduce erythema of rosacea.
OBJECTIVE: To assess the efficacy and safety of topical brimonidine tartrate gel 0.5% for the treatment of erythema of rosacea.
METHODS: Both studies were randomized, double-blind, and vehicle-controlled, with identical design. Subjects with moderate to severe erythema of rosacea were randomized 1:1 to apply topical brimonidine tartrate gel 0.5% or vehicle gel once-daily for 4 weeks, followed by a 4-week follow-up phase. Evaluations included severity of erythema based on Clinician’s Erythema Assessment and Patient’s Self-Assessment, as well as adverse events.
RESULTS: Topical brimonidine tartrate gel 0.5% was significantly more efficacious than vehicle gel throughout 12 hours on days 1, 15,
and 29, with significant difference observed as early as 30 minutes after the first application on day 1 (all P<.001). No tachyphylaxis,
rebound or aggravation of other disease signs were observed. Slightly higher incidence of adverse events was observed for topical
brimonidine tartrate gel 0.5% than for vehicle; however, most of the adverse events were dermatological, mild, and transient in nature.
LIMITATIONS: These data generated in controlled trials may be different from those in clinical practice.
CONCLUSIONS: Once-daily brimonidine tartrate gel 0.5% has a good safety profile and provides significantly greater efficacy relative to
vehicle gel for the treatment of moderate to severe erythema of rosacea, as early as 30 minutes after application.
J Drugs Dermatol. 2013;12(6):650-656.
James J. Leyden MD,a Suzanne Bruce MD,b Chai Sue Lee MD,c,* Mark Ling MD PhD,d Pranav B. Sheth MD,e Daniel M. Stewart DO,f William P. Werschler MD,g Richard D. Gilbert PhD,h and Leon Kircik MDi
BACKGROUND: Doxycycline calcium (WC2055) is a drug substance with a possible role in the treatment of acne. The objective of this
study was to evaluate the safety and efficacy of three doses of doxycycline calcium tablets compared with placebo in the treatment of
moderate to severe inflammatory facial acne vulgaris.
METHODS: This was a randomized, double-blind, phase 2 dose-ranging study in subjects with moderate to severe inflammatory acne
aged 12 years to 45 years. Subjects were randomized to receive doxycycline calcium tablets 0.6, 1.2, or 2.4 mg/kg/day or placebo, and
instructed to take their tablets once daily for 12 weeks, in the evening at least 1 hour before or 2 hours after mealtime. The primary efficacy variables were the dichotomized Investigator's Global Assessment score (success or failure) at week 12 (success defined as ≥2
score decrease from baseline) and the absolute change from baseline to week 12 in inflammatory lesion count.
RESULTS: A dose-response effect was seen with doxycycline calcium formulation in subjects with moderate to severe inflammatory
acne. The highest dose-group (corresponding to approximately 2.4 mg/kg/day) showed a statistically significant difference from placebo.
The dose-response effect was confirmed by logistic regression analysis for both treatment success and incidence of gastrointestinal
adverse events. A limitation of this study is that safety and efficacy were only studied on moderate to severe inflammatory acne.
Also, the study was not prospectively powered to show efficacy differences.
CONCLUSION: Doxycycline calcium shows a dose-response effect in reducing inflammatory lesions in subjects with moderate to severe
J Drugs Dermatol. 2013;12(6):658-663.
Todd E. Schlesinger MD FAADa and Callie Rowland Powell BSN RNb
OBJECTIVE: Rosacea is a chronic cutaneous disorder characterized by flushing, erythema, telangiectasia, edema, papules, and pustules.
The cause of this inflammatory disorder is unknown, but is thought to be multifaceted. Primary treatments for rosacea are typically oral
antibiotics and topical therapies. Hyaluronic acid sodium salt cream 0.2% is a topical device containing low molecular weight hyaluronic
acid (LMW-HA) that is effective in normalizing the cutaneous inflammatory response. The objective of this study was to evaluate the
efficacy and safety of hyaluronic acid sodium salt cream 0.2%.
DESIGN and SETTING: Prospective, observational, non-blinded efficacy and tolerability study in an outpatient setting.
PARTICIPANTS: Individuals 18 to 75 years of age with mild to moderate facial rosacea.
MEASUREMENTS: Outcome measures included papules, pustules, erythema, edema, telangiectasia, burning or stinging, dryness and provider
global assessment (PGA), which were all measured on a five-point scale. Subjects were assessed at baseline, week 2, week 4, and week 8.
RESULTS: Final data for 14 of 15 subjects are presented. Through visual grading assessments, hyaluronic acid sodium salt cream 0.2%
was shown to improve the provider global assessment by 47.5 percent from baseline to week 4. Reductions in papules, erythema,
burning or stinging, and dryness were 47, 51.7, 65, and 78.8 percent, respectively at week 4. At week 8, the provider global assessment
was improved from baseline in 78.5 percent of subjects.
CONCLUSION: Improvement was noted in measured clinical parameters with use of topical low molecular weight hyaluronic acid. Topical
low molecular weight hyaluronic acid is another option that may be considered for the treatment of rosacea in the adult population.
Compliance and tolerance were excellent. Consideration should be given to use for individuals with rosacea characterized by an erythematous
and/or papular component.
J Drugs Dermatol. 2013;12(6):664-667.
Nicholas B. Countryman MD MBA,a* Ross M. Levy MD,b, C.William Hanke MDa
Microscopic interpretation represents the central tenet for diagnosis and eradication of cutaneous tumors. Standard microscopes are
limited by relatively high-powered objectives and smaller viewable diameter. Newer equipment offers optional lower powered objectives
including 1X and 2X objectives and can be combined with super widefield eyepieces to greatly enhance the viewable area during pathologic
interpretation of slides. Mohs micrographic surgery represents one of the most useful areas in which the dermatologic surgeon gleans
multiple efficiencies from these microscope systems. One such system that was recently trialed, the Nikon 80i microscope, proved to be
incredibly easy to use and multiple efficiencies were quickly realized.
J Drugs Dermatol. 2013;12(6):668-671.
Shawn Shetty MD and A. Razzaque Ahmed MD DSc
The objective of this review was to critically analyze the currently available literature on the use of rituximab to treat patients with bullous
pemphigoid (BP). The focus was to highlight clinical outcomes, treatment protocols, and adverse effects. A PubMed search from 2000 to
the present day was conducted, using “bullous pemphigoid” and “rituximab” as keywords. Inclusion criteria were a description of the clinical
disease, histology and immunopathology typical of BP, the use of at least 1 infusion of rituximab, and the availability of follow-up after
rituximab treatment. Sixteen patients (12 adults and 4 children) were identified. Fourteen patients were treated according to the Lymphoma
Protocol and 2 patients according to the Rheumatoid Arthritis Protocol. In the final clinical outcome after treatment with rituximab, 11 out of
16 (69%) had Complete Response, 1 (6%) had Partial Response, 1 (6%) had No Response, and 3 (19%) died. Two died of sepsis, including 1
child, and 1 died from cardiac effects. Three (20%) had serious infections. More than 1 cycle of rituximab was required in 38% of the patients
who achieved Complete Response. The mean follow-up period was 15.6 months (range 1–36), which is a serious limitation of the available
data. Rituximab is a useful option for BP patients who are recalcitrant to conventional therapy. A specific protocol for the use of rituximab
to treat BP patients is not yet available. Since infection and mortality rates are of concern, careful and close monitoring may be necessary.
J Drugs Dermatol. 2013;12(6):672-677.
Daniel J. Aires MD JD,a Garth Fraga MD,b Richard Korentager MD,c Coleman P. Richie MD,d Smita Aggarwal MD,e Jo Wick PhD,f and Deede Y. Liu MDa
BACKGROUND: Intravenous immunoglobulin (IVIG) can be used to treat potentially deadly toxic epidermal necrolysis (TEN), milder Stevens
Johnson Syndrome (SJS) and intermediate TEN/SJS overlap. Some formularies now deny IVIG for TEN based on the EuroSCAR
TEN/SJS study that reported a nonsignificant trend toward increased mortality in 75 IVIG-treated TEN/SJS patients; of note the IVIG
patients had more TEN and less SJS than patients in other treatment arms. EuroSCAR data on mortality among the 25 IVIG-treated
TEN patients, use of nonsucrose IVIG, and admission to specialized settings such as burn units was not disclosed. The impact of
treatment setting (specialized unit vs general ward) on IVIG efficacy has not previously been studied.
OBJECTIVE: To evaluate efficacy of treating TEN with early nonsucrose IVIG in a burn unit.
METHODS: Data were retrospectively collected from 13 IVIG-treated TEN patients admitted to a burn unit over a 6-year period.
RESULTS: We report 0% mortality among 13 IVIG-treated TEN patients. Mortality was significantly lower than predicted by SCORTEN.
Mortality was also significantly lower than the EuroSCAR groups receiving IVIG (P<.005), supportive care (P<.018), and corticosteroids
CONCLUSION: TEN patients may benefit from early nonsucrose IVIG administered in burn units or other specialized settings.
J Drugs Dermatol. 2013;12(6):679-684.
Cindy Wassef BA,a Adriana Lombardi MD,b Sairah Khokher MD,c and Babar K. Rao MDc
INTRODUCTION: Vitiligo is a condition caused by the destruction of melanocytes, resulting in areas of skin without pigmentation. While many
topical therapies exist for its treatment, not all patients respond to such treatments. Various surgical, laser and other alternative therapies
are available for use as well.
OBJECTIVE: The objective of this review was to describe the various surgical, laser, and alternative therapies available for vitiligo. A literature
review was conducted through Pubmed and Ovid using the search terms "Vitiligo treatment”, “Vitiligo surgery”, “Vitiligo laser”. Since no articles
were available about needling on both Pubmed and Ovid using the search criteria, individual articles were sought out through Google.
RESULTS: The literature review yielded many possible surgical interventions including autologous mini-punch grafting, suction epidermal blister
grafting, split-thickness grafting, and cultured and noncultured melanocyte keratinocyte transfer. Laser options included the helium-neon
and xenon-chloride lasers, with tattooing and needling serving as other options. While all the above techniques can provide improvement to
pigmentation in vitiliginous patches, physician comfort and experience are important factors with regards to outcome. Our case series of
four patients treated with the needling method yielded favorable results, with repigmentation rates ranging from 25-50%, with one patient
having 90% repigmentation.
CONCLUSION: There are many surgical, laser, and alternative treatment options available for vitiligo when conventional medical therapy fails
or for use in conjunction with medical therapies. Autologous mini punch grafting and needling both have minimal equipment requirements
and are easy to learn. Physician experience and comfort play a large role in outcome and availability of services.
J Drugs Dermatol. 2013;12(6):685-691.
Sandra P. Ramírez MD,a Alfonso C. Carvajal MD,b Juan C. Salazar MD,c Gladys Arroyave MD,d Ana M. Flórez MD,e and Hector F. Echeverry MDf
Melasma is a cutaneous disorder that primarily affects females of Hispanic and Asian descent. Previous studies have shown that
use of a brightening system comprised of 0.01% decapeptide-12 cream, an antioxidant cleanser, a 20% buffered glycolic acid lotion,
and a broad spectrum SPF 30 sunscreen yields good clearance of mild-to-moderate melasma in Caucasian and Asian volunteers.
The present open-label, prospective, and multicenter study sought to determine the tolerability and efficacy of the above-mentioned
brightening system on mild-to-moderate melasma in 33 Hispanic females over 16 weeks. Clinical measures included self-assessment
of tolerability, clinical grading, determination of Melasma Area and Severity Index (MASI) scores, and standardized clinical
photography. Results showed that the system was well tolerated with no adverse events reported. Mean decreases of 36%, 46%,
54%, and 60% in MASI scores were observed at weeks 4, 8, 12, and 16, respectively, which were further corroborated by standardized
photography showing visible reduction in the appearance of melasma. Results suggest that the brightening system consisting
of 0.01% decapeptide-12 cream, an antioxidant cleanser, 20% buffered glycolic acid lotion, and broad spectrum SPF 30 sunscreen
is safe and efficacious for the treatment of mild-to-moderate melasma in Hispanic females.
J Drugs Dermatol. 2013;12(6):e106-e110.
Martina Kerscher MD,a Yana Yutskovskaya MD,b and Timothy Corcoran Flynn MDc
IncobotulinumtoxinA (Xeomin®/Xeomeen®/Bocouture®/XEOMIN Cosmetic™) is a botulinum toxin type A that differs from other commercially
available botulinum toxin type A preparations in that it is free from complexing proteins ([150 kDa]/NT 201). The proven efficacy
of incobotulinumtoxinA in various therapeutic indications preceded its use in the field of esthetic medicine, where it is widely approved
for the treatment of glabellar frown lines on the basis of positive efficacy and safety findings from a number of clinical trials. Here, we
discuss the characteristics of incobotulinumtoxinA and review the clinical data supporting its use in esthetics.
J Drugs Dermatol. 2013;12(6):e111-e120.