Salman M.S. Alsaad MDa and Maryann Mikhail MDb
Background: Periocular "dark circles" fall among the most difficult chief complaints to address. In most cases, we have little information regarding etiology and no gold-standard treatment option. The extent of the problem is reflected in the sheer number of products on the market advertised to either lighten or cover the pigmentation.
Objective/Methods: To present dermatologists with a complete review of the literature with regard to anatomy, definition, etiology, and treatment of periocular hyperpigmentation.
Conclusions: Our understanding of the causes and treatment of periocular hyperpigmentation continues to advance. Nevertheless, we are in need of additional controlled clinical trials and novel therapeutic options. Individual patients will likely benefit most from a combination of approaches. Although more randomized clinical studies are necessary, Pfaffia paniculata/Ptychopetalum olacoides B.⁄Lilium candidum L. - associated compound cream seems to be a promising option, with 90% improvement. For patients with increased melanin deposition, quality-switched ruby laser therapy could offer a better treatment option. In the hands of experienced professionals, a surgical option might be suitable, either by autologous fat transplantation or hyaluronic acid filler.
J Drugs Dermatol. 2013;12(2):154-157.
Salman Bin Dayel MDa and Khalid AlGhamdi MDb
Background: Vitiligo is a common acquired pigmentary disorder with a profound psychosocial impact. The exact pathogenesis of vitiligo is not fully understood; however, vitiligo appears to be an autoimmune disease involving T-cell-mediated melanocyte destruction. Recently, complete clearance of coexisting vitiligo without recurrence over 2 years was reported in 2 psoriasis patients treated with alefacept.
Objective: To evaluate the safety and efficacy of alefacept in the treatment of vitiligo.
Methods: After providing informed written consent, 4 adult patients with widespread vitiligo (covering a body surface area ≥5%) were treated with weekly intramuscular injections of 15 mg alefacept for 12 weeks. All patients were monitored clinically, by laboratory investigation, and by digital image analysis. All patients were followed up with for 24 weeks.
Results: All patients tolerated alefacept well, without any adverse events. None of the patients showed any repigmentation. However, 1 patient developed new depigmented patches during treatment with alefacept.
Limitations: A pilot study with a small number of patients.
Conclusion: Alefacept as a monotherapy for vitiligo treatment did not result in any patient improvement, and further evaluation in larger studies may be required.
J Drugs Dermatol. 2013;12(2):159-161.
Adisbeth Morales-Burgos MD,a,b Michael P. Loosemore MD, a,band Leonard H. Goldberg MDa-c
An appropriate selection of topical agents for wound care is important to promote uncomplicated healing. Petrolatum-based ointments, such as Aquaphor Healing Ointment (AHO) and white petroleum jelly, are commonly employed to keep wounds moist postoperatively. While they have beneficial properties for wound healing, they also may cause wound redness and swelling. We decided to evaluate for wound reactivity postoperatively for these 2 commonly used petrolatum-based ointments. We found that surgical wounds treated with AHO had a higher incidence of wound redness (52%) than those treated with plain white petrolatum (12%).
J Drugs Dermatol. 2013;12(2):163-164.
Xuejun Zhu MD,a Min Zheng MD PhD,b Michael Song MD,c Yaung-Kaung Shen PhD,dDaphne Chan PhD MHEcon,c Philippe O. Szapary MD MSCE,c and Baoxi Wang MDe on behalf of LOTUS investigators*
Background: Available biologic agents for the treatment of psoriasis in China are limited.
Objectives: The LOTUS study is a phase 3, double-blind, placebo-controlled study that evaluated the efficacy and safety of ustekinu-mab in Chinese patients with moderate to severe plaque-type psoriasis.
Patients and Methods: Patients (n=322) were randomized to receive ustekinumab 45 mg or placebo at weeks 0 and 4, with placebo crossover to ustekinumab at week 12; all patients were followed up to week 36. The primary end point was the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) at week 12. Other end points at week 12 included the proportion of patients with a Physician's Global Assessment (PGA) score of 0 or 1 and the change in Dermatology Life Quality Index (DLQI) score from baseline.
Results: At week 12, 82.5% of ustekinumab-treated patients achieved PASI 75 responses compared with 11.1% of placebo-treated patients (P<.001). Clinical responses were maintained through week 28, with maximum responses observed at week 24. Significant improvements in PGA and DLQI were observed at week 12 and were generally maintained through week 28. At week 12, adverse events rates were similar between groups (45 mg: 42.5% vs placebo: 38.5%), and serious adverse events were reported in 0.6% of patients in each group. Through week 36, no cases of active tuberculosis, serious infections, malignancies, or major adverse cardiovascular events were reported.
Conclusions: Consistent with results previously reported in global phase 3 studies, ustekinumab was highly effective and generally well tolerated in Chinese patients with moderate to severe psoriasis through 36 weeks.
J Drugs Dermatol. 2013;12(2):166-174.
Joel L. Cohen MDa and E. Victor Ross MDb
Background: Fractional ablative and nonablative lasers are useful tools for facial rejuvenation; however, ablative lasers require a period of downtime during reepthelialization. A procedure that combines both ablative and nonablative lasers may deliver good cosmetic results and reduce downtime or other side effects of treatment.
Objective: The purpose of this study was to compare a combined fractional ablative and nonablative laser procedure to ablative-only procedures for facial rejuvenation.
Methods: A total of 8 subjects in 2 study groups received a single, split-face, facial rejuvenation procedure in this study. In group A, we compared a combined procedure using a fractional nonablative 1,440-nm neodymium-doped yttrium aluminum garnet (YAG) laser and a fractional ablative 2,940-nm erbium (Er)-doped YAG laser on one side of the face, and a combined confluent/fractional ablative Er:YAG laser on the other. In group B, we compared the same 1,440/2,940 treatment as group A on one side of the face, and a fractional ablative CO2 laser on the other. Subjects were followed for 3 months to assess side effects and improvement in Fitzpatrick Wrinkle Score and pigmentation.
Results: Improvement in wrinkles and pigment were seen with all techniques in both groups, and results were equivalent. Areas treated with combined fractional nonablative and ablative technique demonstrated fewer immediate side effects.
Conclusion: Facial rejuvenation using a combination treatment of fractional ablative 2,940 and nonablative 1,440 lasers provides improvement in wrinkles and pigment similar to conservative purely ablative approaches. These purely ablative approaches include the Er:YAG laser used in a sequential confluent fractional manner, or fractional CO2 laser alone. Reduced side effects make the combined procedure an attractive option for facial rejuvenation.
J Drugs Dermatol. 2013;12(2):175-178.
Lawrence Green MD,a Leon H. Kircik MD,b-d and Jennifer Gwazdauskas MBAe
Background: Acne vulgaris is a common dermatologic disease that most frequently affects adolescents and young adults. Over-the-counter (OTC) acne treatment regimens are increasingly being used by individuals with acne.
Objectives: To compare the efficacy, user satisfaction, and tolerability of the OTC regimens MaxClarity™, Proactiv®, and Murad® in the treatment of mild and moderate acne.
Methods: Two randomized, evaluator-blinded, split-face studies were conducted, each involving 20 subjects with acne, to evaluate MaxClarity against Proactiv (study 401) and MaxClarity against Murad (study 404) over 8 weeks.
Results: Clinically and statistically significant reductions in acne lesion counts were achieved at 8 weeks compared with baseline for each regimen using MaxClarity, Proactiv, and Murad. Similar reductions in lesion counts and improvements in Investigator's Static Global Assessment grades were observed between MaxClarity and either Proactiv or Murad, in the respective studies. MaxClarity was well tolerated, with no treatment-related adverse events observed in any treatment group and no discontinuations due to adverse events. Overall, most subjects were satisfied with all study treatments.
Conclusions: MaxClarity is an effective alternative to either Proactiv or Murad for use in the treatment of mild and moderate acne.
J Drugs Dermatol. 2013;12(2):180-185.
Eduardo H. Tschen MD,a Alicia D. Bucko DO,a Norihide Oizumi MS, Hideki Kawabata MS,Jason T. Olin PhD, and Radhakrishnan Pillai PhD
Background: Onychomycosis is a common nail infection that is difficult to treat successfully. The prevalence increases with age and is associated with diabetes. Oral treatments are limited by drug interactions and potential hepatotoxicity; topical treatments, by modest efficacy.
Objective: We investigated the efficacy and safety of a solution using a novel topical triazole antifungal, efinaconazole, in distal lateral subungual onychomycosis (DLSO).
Methods: Multicenter, randomized, double-blind, vehicle-controlled phase 2 study in mild to moderate toenail DLSO (n=135). Subjects randomized (2:2:2:1 ratio) to receive efinaconazole 10% solution (with or without semiocclusion), efinaconazole 5% solution, or vehicle, once daily for 36 weeks, with one 4-week posttreatment follow-up (week 40). Efficacy assessments included complete cure, mycologic cure, clinical efficacy, and other assessments of overall treatment effectiveness. No efficacy variables were designated as primary.
Results: At follow-up, complete cure was numerically higher in all active groups (16%-26%) compared with vehicle (9%). Mycologic cure rates with efinaconazole 10% semiocclusion, efinaconazole 10%, and efinaconazole 5% were 83%, 87%, and 87%, respectively. Efinaconazole 10% (with or without semiocclusion) demonstrated significantly greater clinical efficacy and treatment effectiveness when compared with vehicle (P=.0088 and .0064; .0056 and .0085, respectively, for both efinaconazole 10% groups). Adverse events were generally similar and mild. Local-site reactions were restricted to few subjects and did not differ meaningfully from those produced by vehicle.
Conclusions: This study provided evidence that once-daily efinaconazole 10% solution (with or without semiocclusion) applied topically for 36 weeks was more effective than vehicle in treating DLSO and was well tolerated. Based on these results, efinaconazole 10% solution was chosen for the phase 3 development program.
J Drugs Dermatol. 2013;12(2):186-192.
Claire Battie PharmD,a Mona Gohara MD,b Michèle Verschoore MD,a and Wendy Roberts MDc
For many fair-skinned individuals around the world, skin cancer is the leading malignancy. Although skin cancer comprises only 1% to 2% of all malignancies in those with darker complexions, the mortality rates in this subgroup are substantially higher when compared with their Caucasian counterparts. This discrepancy is largely as a result of delayed detection/treatment, and a false perception among patient and physician that brown skin confers complete protection against skin cancer. Recent studies show that 65% of surveyed African Americans never wore sunscreen, despite living in sunny climates, and that more than 60% of minority respondents erroneously believed that they were not at risk for skin cancer.
Dark skin offers some protection from ultraviolet (UV) light. However, there is considerable heterogeneity in skin of color, a phenomenon that is accentuated by mixed heritage. Ethnicity does not confer skin type anymore. People of color do experience sunburn, and from a biological point of view, all skin types appear to be sensitive to UV-induced DNA damage, with an inverse relationship between skin color and sensitivity to UV light.
Our population is changing rapidly, and within the next few decades minority populations will become the majority. It is therefore imperative to educate both physicians and patients on the perceived immunity against cutaneous malignancies, the need for sun protection, and the clinical signs of skin cancer in non-Caucasian people, so that future unnecessary mortality can be avoided.
J Drugs Dermatol. 2013;12(2):194-198.
Oge C. Onwudiwe MD,a Ellen S. Marmur MD,b and Joel L. Cohen MDc
Herpes simplex virus (HSV) prophylaxis may be underutilized in cosmetic surgery at a time when cosmetic procedures are increasing. Our goal is to review the data regarding HSV prophylaxis in order to remind cosmetic surgeons when to consider adding this regimen to their patient perioperative care.
J Drugs Dermatol. 2013;12(2):199-205.
Barry Ladizinski MD,a Misha M. Heller BA,b Tina Bhutani MD,c Kristine B. Zitelli MD,c and John Y. M. Koo MDc
Progressive multifocal leukoencephalopathy (PML) is a frequently fatal demyelinating disease of the brain caused by activation of the John Cunningham virus. It typically occurs in immunocompromised patients, including transplant recipients on immunosuppressant medications, patients receiving chemotherapy for hematologic malignancies, and patients with human immunodeficiency virus. Unfortunately, there is no effective treatment for PML. By contrast, reversible progressive leukoencephalopathy syndrome (RPLS) is a generally treatable disorder that is diagnosed based on clinical symptoms (eg, altered mental status, visual abnormalities, headache, and seizures) and neuroradiographic changes (eg, cerebral edema). It is classically associated with malignant hypertension and immunosuppressive medications. Symptoms usually resolve over time, or with treatment of the underlying cause. Amid the relatively recent withdrawal of efalizumab from the US market because of its association with PML, and the added warning found on ustekinumab describing RPLS as a possible adverse effect, there has been an increasing level of concern in dermatology that biologics and other systemic medications used in the treatment of psoriasis may be related to an increased risk of specific leukoencephalopathies. In this review, we evaluate the association of prebiologics (eg, cyclosporine, methotrexate, acitretin) and biologics (eg, adalimumab, alefacept, efalizumab, etanercept, infliximab, rituximab, and ustekinumab) with the potential risk of developing PML and RPLS.
J Drugs Dermatol. 2013;12(2):e20-e24.
Dalia G. Aly MD,a Ihab Y. Abdallah MD,b Noha S. Hanafy MD,a Mohamed L. Elsaie MD,a,c and Neveen A. A. Hafizd
Background: Leptin, an adipocyte-derived hormone, has been shown to have several immunological effects similar to those of proinflammatory cytokines. The relationship between serum leptin, psoriasis, and obesity is still conflicted, and very few studies have investigated its role in skin diseases other than psoriasis.
Aim: To evaluate the possible relationship between serum leptin in nonobese patients with psoriasis and other randomly selected skin diseases.
Subjects and methods: Eighty subjects (40 patients with psoriasis, 20 patients with other randomly selected skin diseases, and 20 healthy controls) were included in the study. Fasting serum leptin levels of the study groups were examined by sandwich enzyme-linked immunosorbent assay.
Results: Elevated serum leptin levels were detected in both nonobese patients with psoriasis (P=.004) and those with other randomly selected skin diseases (P=.05). Leptin levels failed to correlate to the Psoriasis Area and Severity Index score of psoriatic patients. Both sexes demonstrated comparable levels of serum leptin in psoriatic patients, while female patients suffering from other skin diseases showed higher levels of serum leptin than did males of the same group.
Conclusion: Leptin may play a role in the immunopathogenesis of psoriasis and other skin diseases, even in the absence of obesity as a cofactor.
J Drugs Dermatol. 2013;12(2):e25-e29.
Faris Azzouni MD,a Nathalie Zeitouni MD PhD,b and James Mohler MDa
5α-reductase (5α-R) isozymes are ubiquitously expressed in human tissues. This enzyme family is composed of 3 members that perform several important biologic functions. 5α-R isozymes play an important role in benign prostate hyperplasia, prostate cancer, and androgen-stimulated skin disorders, which include androgenic alopecia, acne, and hirsutism. Discovery of 5α-R type 2 deficiency in 1974 sparked interest in development of pharmaceutical agents to inhibit 5α-R isozymes, and 2 such inhibitors are currently available for clinical use: finasteride and dutasteride. 5α-R inhibitors are US Food and Drug Administration (FDA)-approved for the treatment of benign prostate hyperplasia. Only finasteride is FDA-approved for treatment of male androgenic alopecia. This article reviews the pathophysiology of androgen-stimulated skin disorders and the key clinical trials using 5α-R inhibitors in the treatment of androgen-stimulated skin disorders.
J Drugs Dermatol. 2013;12(2):e30-e35.
Aman Samrao MD,a Jennifer M. Fu MD,a,b Steven T. Harris MD,b and Vera H. Price MDa
Background: Intralesional corticosteroid injections are a common treatment for patchy alopecia areata, the most prevalent subtype of this autoimmune hair disorder. To date, no studies have examined the potential adverse effects of this therapy on bone mineral density (BMD).
Methods: In this retrospective, cross-sectional case series, 18 patients with patchy alopecia areata treated at 4- to 8-week intervals with intralesional triamcinolone acetonide for at least 20 months were evaluated for BMD using dual-energy x-ray absorptiometry (DXA). Follow-up DXA measurements were obtained in those with abnormal findings.
Results: Nine out of 18 patients (50%) had abnormal DXA results. Patients with the following risk factors were more likely to have abnormal BMD: age older than 50 years, body mass index less than 18.5 kg/m2, lack of weight-bearing exercise, smoking history, postmenopausal status, past stress fracture, family history of osteopenia or osteoporosis, and a cumulative intralesional triamcinolone acetonide dose of greater than 500 mg.
Conclusion: Patients with patchy alopecia areata who receive chronic intralesional triamcinolone acetonide therapy should be counseled on preventive measures for osteoporosis and monitored for effects on BMD.
J Drugs Dermatol. 2013;12(2):e36-e40.