James Q. Del Rosso DO FAOCD, Suzanne Bruce MD, Michael Jarratt MD, Alan Menter MD, Gerald Staedtler
Rosacea is a leading reason why people seek the care of a dermatologist, accounting for nearly 7 million office visits annually. Pharmacologic
treatments include both topical and oral medications, which are increasingly being used in combination, especially at the
outset of therapy. This exploratory study assesses the safety, effectiveness and speed of onset of two common topical agents for
the treatment of rosacea—azelaic acid gel (AzA) 15% and metronidazole gel 1%—used in conjunction with anti-inflammatory dose
doxycycline (40 mg once daily).
Men and women (n=207) with mild-to-moderate papulopustular rosacea were enrolled and randomized to receive either AzA gel 15%
twice daily plus doxycycline 40 mg once daily (AzA group) or metronidazole gel 1% once daily plus doxycycline 40 mg once daily
(Metro group) for 12 weeks. Both regimens were safe, efficacious and well tolerated. Efficacy parameters revealed a possible trend
toward greater and earlier benefit with the AzA-based regimen than with the metronidazole-based regimen. These findings warrant
further investigation in a sufficiently powered study.
Grace K. Kim DO and James Q. Del Rosso DO FAOCD
There are some patients that, despite their continued use of optimized topical and systemic medication and skin care regimens, exhibit
at least partial persistence of acne vulgaris (AV) lesions that is bothersome and treatment-resistant to pharmacologic approaches.
Additionally, professional, public and governmental concern regarding “antibiotic resistance” has led to interest in therapeutic
alternatives other than antibiotics. These challenges drive research into non-pharmacologic approaches to AV treatment, including
laser and light-based approaches.
Background: Topical treatment of acne vulgaris on the back is challenging largely due to the extensive broad surface with difficult
to reach areas. A “leave-on” foam is suited for application to the trunk due to ease of application and spreadability. Prior to this trial,
no data on Propionibacterium acnes (P. acnes) reduction on the back has existed for any benzoyl peroxide (BP) formulations or other
Objectives: To evaluate the effectiveness of BP (5.3%) emollient foam and BP (8%) wash in reducing P. acnes levels on the back.
Methods: Five-week open-label single-center study of 20 healthy subjects (>18 years old), colonized with P. acnes on their backs
(>10,000 colonies per cm2). Subjects were treated once daily with BP (5.3%) foam for two weeks; no treatment in week 3, and BP
(8%) wash once daily for two further weeks. Quantitative bacteriologic cultures obtained at baseline and weeks 1, 2, 3, 5 and 6.
Results: Nineteen evaluable patients. Total P. acnes counts were reduced by 1.9 log (one week) and 2.1 log (two weeks) with BP
(5.3%) emollient foam. BP (8%) wash did not reduce P. acnes counts after two weeks.
Discussion: BP (5.3%) emollient foam was superior to BP (8%) wash in reducing P. acnes on the back. The lack of effect of BP (8%)
wash is surprising in view of the demonstrated results on the face and warrants further study.
Saira B. Momin DO , Aaron Peterson DO , James Q. Del Rosso DO FAOCD
Several drugs have been associated with the development of eruptions that may simulate acne vulgaris. These drugs include corticosteroids,
epidermal growth factor receptor inhibitors, cyclosporine, anticonvulsants, antipsychotics, antidepressants, tumor necrosis
factor-α (TNF-α) inhibitors, anabolic steroids, danazol, antituberculosis drugs, quinidine, azathioprine and testosterone. In some
cases, the eruption is clinically and histologically similar to acne vulgaris while, in other cases, the eruption is clinically suggestive of
acne vulgaris without any histologic information. Additionally, in other cases of drug-associated acneiform eruptions, despite clinical
similarity, histologic features are not consistent with acne vulgaris.
Lawrence F. Eichenfield MD,a Michael Jarratt MD,b Joel Schlessinger MD,c Steven Kempers MDd, Vasant Manna MDe, Joyce Hwa RN BSNe, Yin Liu PhDe, Michael Graeber MDe, on Behalf of the Adapalene Lotion Study Group
Background: Acne vulgaris is a common chronic skin disease affecting roughly 15 percent of the general population and up to 85
percent of adolescents and young adults. Adapalene, a synthetic naphthoic acid derivative with retinoid activity, has demonstrated
good clinical efficacy in the treatment of acne if used with full compliance.
Objectives: To evaluate the efficacy and assess safety of a new adapalene formulation, adapalene 0.1% lotion, versus the lotion
vehicle in subjects with acne vulgaris.
Methods: Subjects were randomized to receive either adapalene 0.1% lotion or its vehicle once daily for 12 weeks in two multicenter,
randomized, vehicle-controlled, double-blind, parallel group studies. Efficacy was evaluated using two co-primary endpoints:
Investigator Global Assessment (IGA) of success rate (defined as the proportion of subjects who achieved at least a two point reduction,
on a 5-point scale, from baseline to week 12 in IGA score); and the absolute change from baseline to week 12 in total, inflammatory
and non-inflammatory lesions. Signs of local skin irritation and routine clinical safety parameters were evaluated throughout
Results: In total, 2,141 subjects were included in the two studies: 1,068 patients received adapalene 0.1 percent lotion and 1073
received the vehicle. In both studies, adapalene 0.1% lotion was shown to be significantly more effective than its vehicle in improvement
in the IGA success rate. Adapalene 0.1% lotion was also significantly superior to its vehicle in all three lesion reduction
measures: total, inflammatory and non-inflammatory. Reports of application site skin irritation in the adapalene 0.1% lotion treatment
group were transient and mild or moderate in severity, with only a few being severe. Additionally, according to patient surveys, the
lotion formulation was found to be easily spreadable, easily absorbed and pleasant to use.
Conclusion: Adapalene 0.1% lotion used once a day for 12 weeks is effective and well tolerated in the treatment of acne vulgaris.
Anne Marie Tremaine MD, Arisa Ortiz MD, Laila Elkeeb MD, Minh Tran, Gerald Weinstein MD
Background: Many patients with rosacea cannot tolerate extended treatment periods with topical agents because their skin sensitivity
is often increased.
Objective: To determine the long-term efficacy and tolerability of a new moisturizing lotion for improving the signs and symptoms
of mild-to-moderate rosacea.
Methods: In a 48-week, open-label study, a moisturizing lotion containing furfuryl tetrahydropyranyladenine as PRK-124 (0.125%,
Pyratine-XR™, Senetek PLC, Napa, CA) was applied twice daily by 18 subjects with mild-to-moderate rosacea. Clinical improvements
were assessed by the treating physician. Skin barrier function was measured by transepidermal water loss after treatment. Tolerability
and cosmetic outcome were evaluated by subjects.
Results: Subjects experienced a mean 44 percent reduction in erythema severity and a mean 89 percent reduction in inflammatory
lesion count at week 48. Reductions were significant (P≤0.05) in both erythema and lesions at weeks 24, 36 and 48. Statistically significant
(P≤0.05) improvements in telangiectasias, transepidermal water loss and dryness were noted. Overall clinical improvement
was observed in 81 percent of subjects and the investigator’s global assessment steadily improved throughout the study. Treatments
were well-tolerated and cosmetically acceptable. Treatment-induced skin irritation was not observed.
Conclusion: The new moisturizing lotion containing furfuryl tetrahydropyranyladenine as PRK 124 is efficacious, does not irritate skin,
and is well tolerated for at least 48 weeks.
Mital Patel MD, Whitney P. Bowe MD, Carol Heughebaert MD, Alan R. Shalita MD
Objective: To review recent studies on the use of antibiotics in acne vulgaris which provide insight into the development of antimicrobial
Data sources: Sources for this article were identified by searching the English literature by Medline for the period 1960 to March 2009.
Study selection: The following relevant terms were used: acne, acne vulgaris, acne and antibiotic therapy, acne and antimicrobial
resistance, acne and resistance mechanisms, acne and systemic infections, acne and antibiotic resistance and coagulase-negative
Staphylococcus aureus (S. aureus), acne and antibiotic resistance and upper respiratory infection.
Data synthesis: Both correct and incorrect use of antibiotics for acne vulgaris can promote antimicrobial resistance. The development
of this resistance is promoted by several factors, including antibiotic monotherapy, long-term administration of antibiotics, indiscriminate
use outside their strict indications, dosing below the recommended levels, and the administration of antibiotics without
concurrent benzoyl peroxide and/or topical retinoids.
Conclusion: Long-term use of antibiotics in the treatment of acne vulgaris can lead to antimicrobial resistance with serious and intractable
problems not limited to Propionibacterium acnes (P. acnes), the skin and acne vulgaris themselves, but also to other bacterial
species, with systemic consequences. These findings suggest that antibiotics should be prescribed in combination with benzoyl
peroxide and/or topical retinoids and be limited to a maximum of several months.
Data continue to establish the role of inflammation, not only in the pathogenesis of acne but also in the development of its most devastating
sequelum, scarring. Although topical therapy is preferred by most acne patients and the physicians who treat them, historically
no topical intervention has provided primarily anti-inflammatory effects. Topical dapsone 5% gel offers documented efficacy for
the reduction of both inflammatory and non-inflammatory acne lesions. It has been proven safe, presenting none of the hematologic
risks associated with oral dapsone. Data suggest the vehicle formulation enhances healing and contributes to tolerability, making
topical dapsone 5% gel a worthwhile anti-inflammatory treatment for many patients with mild-to-moderate acne vulgaris.
Irene J. Vergilis-Kalner MD, Adam J. Mamelak MD, Leonard H. Goldberg MD
Vertical undermining for repair of partial thickness defects is a new effective technique that allows the wound edges of partial thickness
defects to be freed and mobilized so that they can be repaired primarily. This technique does not call for the removal of the
residual dermis at the base of the wound, allowing for conservation of the healthy tissues. By leaving the partial thickness dermis in
place, this technique significantly decreases wound- healing times, as well as leads to improved cosmetic outcomes and increased
Carrie Brodmerkel PhD, Yaowei Zhu PhD, Qun Jiao MS, Joel Cornacoff PhD DVM,George Treacy MS, Mary Ann Mascelli PhD, Alice B. Gottlieb MD PhD
Background: Ustekinumab, a fully human immunoglobulin (Ig) G1κ monoclonal antibody directed against the p40 subunit of interleukin
(IL)-12/23, has demonstrated efficacy in patients with moderate-to-severe psoriasis.
Objective: To evaluate the effect of IL-12/23 inhibition on immunocompetency by antigen-recall response in a preclinical multipledose
toxicology study and three single-dose, phase 1 studies.
Methods: Cynomolgus monkeys (Mauritius; n=32) treated with subcutaneous (s.c.) placebo or ustekinumab 22.5 or 45 mg/kg twice
weekly for 26 weeks were assessed for antibody responsiveness to keyhole limpet hemocyanin (KLH). Patients with psoriasis or
multiple sclerosis who received a single-dose of placebo (n=8) or ustekinumab (n=46) 0.09–4.5 mg/kg intravenous (i.v.) or 0.27–2.7
mg/kg s.c. were assessed by pneumococcal and tetanus antigen challenge. Primary T-cell response was not assessed in humans.
Results: Anti-KLH antibody responses in ustekinumab-treated cynomolgus monkeys were comparable to those observed in placebotreated
animals. A normal antibody response (≥two-fold increase from baseline) to pneumococcal antigen was seen in 34/46 (73.9%)
ustekinumab-treated versus 4/8 (50%) placebo-treated patients. A normal antigen-recall response (≥four-fold increase from baseline)
was seen in 12/20 (60%) ustekinumab- and 4/5 (80%) placebo-treated patients following tetanus toxoid exposure. Percentages of
circulating immune cells were not affected by ustekinumab treatment.
Conclusion: Results in nonhuman primates and human patients suggest that ustekinumab treatment does not significantly impair
recall humoral immune system functions.
Fariba Iraji MD, Ali Asilian MD, Amir Hossein Siadat MD
Background: Pemphigus vulgaris (PV) is a chronic, bullous disorder that is usually characterized by the presence of bulla and erosion
on the skin and mucosa. Many studies on PV focus on the use of topical non-steroid agents. One of these agents is pimecrolimus;
its efficacy is established in some inflammatory and autoimmune disorders such as oral and genital lichen planus.
Patients, Materials and Methods: This was a double-blind study that was performed in 11 patients with confirmed diagnosis of
PV. Patients under treatment with systemic steroid and azathioprine who had bilateral symmetrical oral lesions were selected and
right- or left-sided lesions of those identified were randomized to be treated either by pimecrolimus 1% cream or placebo. The largest
diameter of lesions was measured at the baseline and every 15 days for two times. Epithelization Index (EI) was calculated and data
were analyzed with a program for statistical analysis.
Results: Overall, 11 patients (62 cutaneous lesions; 31 lesions in the pimecrolimus group and 31 lesions in the placebo group) with
cutaneous lesions of the pemphigus vulgaris were included in this study. At the end of day 15, there was significant difference regarding
EI between the pimecrolimus and placebo groups. In addition, EI was significantly different at the end of study (day 30) in
favor of pimecrolimus group (P=0.000).
Conclusion: Pimecrolimus can be used as an effective and safe adjunctive treatment for cutaneous lesions of pemphigus vulgaris.
Iron levels are tightly regulated in the body to maintain homeostasis.
When homeostatic mechanisms malfunction, excess
iron accumulation in the body has deleterious effects with important health consequences worldwide. Different degrees of iron accumulation complicate pathological conditions such as hereditary hemochromatosis (HH), porphyria cutanea tarda (PCT), venous stasis ulcers, diabetic wounds, skin cancer and sunburn. Despite the known association of systemic iron excess with cutaneous findings, little is known about the mechanism by which a surplus of systemic iron affects the skin. This paper explores the link between excess iron and dermatologic findings in the conditions listed above in order to illustrate potential mechanisms by which iron overload exacerbates the cutaneous manifestations associated with each disease.
Pipeline Previews brings to you information on the newest drugs and medical products as they become available to the dermatological
community. This department may include additional information from the manufacturers, plus reports from physicians who wish to share
their clinical experience with these new products. In addition, we will inform our readers about the latest drugs receiving Food and Drug
Administration (FDA) approval. We trust you will find this information beneficial to your practice and research.
Winning Poster: Body Image Disturbance
in Patients With Acne Vulgaris
Clinical Trial Review is a JDD department designed to provide physicians with information on drugs undergoing clinical testing. It is our goal to inform the reader of the status of select drug trials relevant to the practice of dermatology before this information is available through standard channels. To participate in or learn more about these and additional trials, visit www.clinicaltrials.gov.