Tatjana Pavicic MD,a Julius W. Few MD,b and Jürgen Huber-Vorländer MDc
Facial aging is a three-dimensional process, and facial rejuvenation procedures intended to reverse the effects of aging need to address this by combining products that relax hyperkinetic musculature, volumize/fill, and recontour/lift the whole face. In line with the desire of patients to achieve an overall youthful facial appearance, we report for the first time three cases where patients have been successfully treated across the whole face with a novel, three-step approach, layering incobotulinumtoxinA and two dermal fillers (calcium hydroxylapatite and a monophasic hyaluronic acid filler with CPM Technology) injected at three separate treatment visits. The results suggest that this layering approach based on an understanding of the underlying causes of facial aging, where different products are used in combination to treat the entire face, can enable patients to achieve the desired outcome of a return to the characteristics of a more youthful face.
J Drugs Dermatol. 2013;12(9):978-984.
Pain is a common patient complaint with dermatologic laser procedures and effective pain management is important for the comfort and satisfaction of patients undergoing these procedures. Many topical anaesthetics are available as options to decrease the pain associated with these procedures, although not all have the same degree of safety. An FDA-approved lidocaine and tetracaine topical anesthetic cream [Pliaglis®, liodocaine and tetracaine 7%/7% cream (LT cream), Galderma Laboratories LP, Fort Worth, TX] is safe and effective when used with common laser therapies such as ablative and nonablative laser resurfacing, laser hair removal, laser treatment of vascular lesions, and laser tattoo removal. LT cream should be considered by dermatologists when choosing a topical anesthetic for laser dermatologic procedures.
J Drugs Dermatol. 2013;12(9):986-989.
Meike Streker MD, Tilmann Reuther MD, Nils Krueger MD PhD, and Martina Kerscher MD
BACKGROUND: Mid-dermal injection of stabilized hyaluronic acid (HA) is well established as a treatment to reduce the effects of skin aging.
OBJECTIVE: To assess the efficacy and safety of a stabilized HA-based gel of non-animal origin manufactured using the patented NASHA® technology (Restylane® Vital Light, Q-Med AB, Uppsala, Sweden) administered using a pre-filled micropuncture injector device for rejuvenation of the skin.
METHODS: Three treatment sessions 4 weeks apart were performed on one side of the face, the dorsum of one of the hands and one side of the decolletage, leaving the other side untreated. Skin quality was assessed via blinded live evaluation and subject satisfaction by questionnaire. Aesthetic change was evaluated independently by the subject and a blinded evaluator. Subjects were followed up to week 36.
RESULTS: Thirty subjects aged 40–65 years were enrolled. Overall skin quality across all three treatment areas was judged to be improved on the treated side in over 80% of subjects throughout the study. Significant aesthetic improvements on the treated sides were observed at all visits, with the exception of the decolletage at week 36.
CONCLUSIONS: This was the first study that used a micropuncture injector device for injection of NASHA gel, and reveals that this is a promising treatment option for rejuvenation of the skin.
J Drugs Dermatol. 2013;12(9):990-994.
Soft tissue fillers are becoming increasingly important as nonsurgical treatment options for facial rejuvenation. Calcium hydroxylapatite (CaHA) is an injectable dermal filler that contains uniform CaHA microspheres suspended in an aqueous carboxymethylcellulose gel carrier. It is considered a long-lasting, but non-permanent filler, and is highly biocompatible with human tissue. No osteogenesis has been reported in extensive literature describing the use of CaHA in a variety of soft tissue applications. Injection of CaHA into the oral mucosa and the lips is an unapproved indication and may result in nodule formation. This occurs soon after injection and is a result of accumulated particles and not a granulomatous reaction. As with all biodegradable dermal fillers, CaHA can be associated with rare incidences of foreign body reactions, but only a handful of case reports have been documented in 10 years of clinical use. CaHA can be associated with local, short-term, injection-related adverse events, which are generally mild and resolve within a few days. Clinical trials that have followed patients for up to 3 years post-injection report no long-term or delayed-onset adverse events. CaHA is an effective and safe treatment option for a variety of aesthetic indications. This paper focuses on common safety concerns of patients and aesthetic physicians, including unfounded fears of osteogenesis and foreign body granulomas, providing an up-to-date overview of the tolerability and long-term safety of CaHA for aesthetic indications.
J Drugs Dermatol. 2013;12(9):996-1002.
Stefan Plaum MD, Amit Verma DrPH MPH, Alan B. Fleischer Jr. MD,
Babajide Olayinka MSc, and Bhushan Hardas MD
BACKGROUND: Two-week treatment using naftifine cream or gel, 2% has been shown to be efficacious in subjects with Tinea pedis and/or Tinea cruris, and in most cases, continued improvement has been observed following cessation of treatment for up to four weeks. One possible explanation for continuous post-treatment improvement is drug-levels remaining in the stratum corneum (SC) as a function of time.
OBJECTIVE: The objective is to use tape stripping methodology to assess the amount of drug available in the SC over a 28 day period following the last dose.
METHODS: This was an open-label, single-exposure study on subjects comparing the amount of drug that was absorbed into the SC following topical application for 2-weeks. Twelve subjects were dosed daily (6 with naftifine cream, 2% and 6 with naftifine gel, 2%). Subjects had twelve 8 cm2 test application sites demarcated on the upper back. Twenty-five individual sequential strips were obtained from each test site. Of these, 11 sites were dosed once daily with the drug (5.0μL/cm2) for days 1 to 14 and the final site served as the control. On days 15, 29, and 43, a site was stripped to collect the SC in order to process the amount of drug present.
RESULTS: Naftifine was present on all tape strip samples collected over the 28 day period following two weeks of application. Furthermore, the most relevant, deeper tape strip sets reflecting the SC, showed potentially clinically relevant presence of naftifine in the skin for 28-days post-treatment.
CONCLUSIONS: Naftifine was present in the tape strips on all sample collection days up to and including four weeks following the last drug application. These findings help explain the progressive improvement in clinical and mycological response rates during the treatment period and for up to four weeks post-treatment in the clinical trials using naftifine.
J Drugs Dermatol. 2013;12(9):1004-1008.
Michael Jarratt MD,a William Jo Siu PhD DABT,b Eiko Yamakawa MS,c
Nobuyuki Kodera MS,c Radhakrishnan Pillai PhD,b and Kathleen Smith MBAb
OBJECTIVES: To characterize the systemic exposure and pharmacokinetics of efinaconazole 10% solution and assess the potential for drug-drug interaction (DDI) in human volunteers and onychomycosis patients following topical administration.
METHODS: Two single-center, open-label studies in healthy volunteers and severe onychomycosis patients. Efinaconazole 10% solution was applied topically to all 10 toenails (0.42 mL total daily dose volume); administered as single and then 7 daily doses to 10 healthy volunteers, and once daily for 28 days to 19 severe onychomycosis patients. Plasma concentrations of efinaconazole and its major metabolite H3 were determined by LC-MS-MS at multiple timepoints. Safety evaluations were carried out throughout both studies.
RESULTS: The mean peak plasma concentrations (Cmax) of efinaconazole and H3 were 0.54 and 1.63 ng/mL, respectively, in healthy volunteers; and 0.67 and 2.36 ng/mL, respectively, in patients. Both parent drug and metabolite accumulated following repeat dosing, and reached steady state in plasma by 14 days. Efinaconazole was well tolerated in both studies; no drug-related adverse events were reported.
CONCLUSIONS: Efinaconazole 10% solution resulted in very low systemic exposures to efinaconazole and H3 when applied topically at maximum use conditions to healthy volunteer and onychomycosis patients’ toenails. Efinaconazole is a CYP inhibitor like other azole antifungals, and its lowest ki is 91 ng/mL for CYP2C9, a >130-fold higher concentration than the mean steady state Cmax observed in patients. The Cmax/ki ratio was 0.007, well below the threshold for clinical DDI evaluation as recommended in regulatory guidances, thereby suggesting efinaconazole 10% solution has remote potential for drug-drug interactions.
J Drugs Dermatol. 2013;12(9):1010-1016.
Enzo Emanuele MD,a Velimir Altabas MD,b Karmela Altabas MD,b and Enzo Berardesca MDc
The exposure to ultraviolet radiation (UVR) is one of the most important risk factors for skin aging and increases the risk of malignant transformation. Telomere shortening and an altered expression of the proto-oncogene c-FOS are among the key molecular mechanisms associated with photoaging and tumorigenesis. Photolyase from A. nidulans and endonuclease from M. luteus are xenogenic DNA repair enzymes which can reverse the molecular events associated with skin aging and carcinogenosis caused by UVR exposure. Therefore, the purpose of this study was to investigate whether the topical application of preparations containing DNA repair enzymes may prevent UVR-induced acute telomere shortening and FOS gene hyperexpression in human skin biopsies. Twelve volunteers (Fitzpatrick skin types I and II) were enrolled for this experimental study, and six circular areas (10 mm diameter) were marked out on the nonexposed lower back of each participant. One site was left untreated (site 1: negative control), whereas the remaining five sites (designated sites 2–6) were exposed to solar-simulated UVR at 3 times the MED on four consecutive days. Site 2 received UVR only (site 2: positive control), whereas the following products were applied to sites 3–6, respectively: vehicle (moisturizer base cream; applied both 30 minutes before and immediately after each irradiation; site 3); a traditional sunscreen (SS, SPF 50) 30 minutes before irradiation and a vehicle immediately after irradiation (site 4); a SS 30 minutes before irradiation and an endonuclease preparation immediately after irradiation (site 5); a SS plus photolyase 30 minutes before irradiation and an endonuclease preparation immediately after irradiation (site 6). Skin biopsies were taken 24 h after the last irradiation. The degree of telomere shortening and c-FOS gene expression were measured in all specimens. Strikingly, the combined use of a SS plus photolyase 30 minutes before irradiation and an endonuclease preparation immediately after irradiation completely abrogated telomere shortening and c-FOS gene hyperexpression induced by the experimental irradiations. We conclude that the topical application of preparations containing both photolyase from A. nidulans and endonuclease from M. luteus may be clinically useful to prevent skin aging and carcinogenesis by abrogating UVR-induced telomere shortening and c-FOS gene hyperexpression.
J Drugs Dermatol. 2013;12(9):1017-1021.
Leon Kircik MD,a,b Firas Hougeir MD,c and Joseph Bikowski MDd
Over the last half century, and especially over the last 15 years, understanding of the structure and function of the stratum corneum has evolved tremendously. Once conceptualized as an inactive film formed by lifeless, disintegrating keratinocytes, the stratum corneum is now recognized as a viable, functional structure that plays an important role in maintaining skin health and possibly mediating cutaneous diseases. Researchers and clinicians have also come to realize that the barrier functions not only to prevent the entry of exogenous factors, such as irritants or allergens, but that it also can mediate disease. We had already realized that dysfunction of the barrier may itself directly contribute to the pathogenesis of skin diseases, notably atopic dermatitis. More specifically, evidence shows that epidermal barrier dysfunction is likely to be a precursor of cutaneous inflammation.1,2
J Drugs Dermatol. 2013;12(9):1024-1027.
Chikoti M. Wheat MD,a Naissan O. Wesley MD,b and Brooke A. Jackson MDc
Sun protective behaviors are not as frequently practiced in skin of color as they are amongst Caucasians.1 Thus providing a reasonable assumption this behavior, or lack thereof, increases the risk of skin cancer in this skin of color populations. The aim of this study was two-fold-- the first was to understand whether patients with skin of color, when categorized by ethnicity or skin type, are able to recognize skin cancer lesions. The second was to examine the correlation between ethnicity and/or skin type and practice of sun protective behaviors. We surveyed 105 respondents presenting for various skin problems in a dermatology office in Chicago, IL. Topics covered in the survey included recognition of skin cancer appearance and choice of sun protective behaviors. We show that there is a tendency for patients to potentially recognize atypical pigmented lesions when they are “dark moles with irregular borders” or “new moles”. In contrast, there is a reduced ability among darkly pigmented skin types IV to VI, to recognize non-melanoma skin cancers. We also show that in addition to ethnicity, skin type within ethnic groups may also play an influential role on the decision to protect or not protect oneself from the sun.
J Drugs Dermatol. 2013;12(9):1029-1032.
S.H. Babaeinejad MD and R.F. Fouladi MD
Topical treatments, such as adapalene and benzoyl peroxide (BPO), are popular in mild-to-moderate acne vulgaris. This study aimed to compare the efficacy, safety and tolerability of adapalene and BPO in mild acne vulgaris. In this single-center, randomized, double-blind, clinical trial, 60 patients with mild acne vulgaris received either topical adapalene 0.1% gel or topical BPO 2.5% gel on their face once daily for two months. The changes of acne lesion count (efficacy), any adverse effect (safety), and the patients’ overall satisfaction (tolerability) were compared after 3 months of follow-up. In both groups the mean number of noninflammatory, inflammatory and total lesions decreased significantly from baseline (10.77±5.54, 9.73±5.09, and 20.50±7.54, respectively in adapalene group; 11.50±5.92, 8.43±5.45, and 19.93±9.01, respectively in BPO group) to the third month (1.70±1.68, 0.33±0.66, and 0.50±0.78, respectively in adapalene group; 4.23±4.14, 0.33±0.71, and 4.13±4.44, respectively in BPO group; P<0.001 for all), posttreatment. Although the mean number of inflammatory lesions was significantly lower in BPO receivers only at first month (P=0.001), the mean number of noninflammatory and total lesions was significantly lower in adapalene group at second (P= 0.04 and 0.03, respectively) and third (P=0.02 and <0.001, respectively) months, posttreatment. The adverse events were minimal and self-limited (26.7% in adapalene group, 20% in BPO group, P=0.54). The patients’ overall satisfaction was good-excellent in 93.3% of adapalene receivers vs. 73.3% in BPO group (P=0.08). Both topical adapalene 0.1% and BPO 2.5% gels seem safe and effective in mild acne vulgaris, with a marginal tendency toward the former.
J Drugs Dermatol. 2013;12(9):1033-1038.
Evren Odyakmaz Demirsoy MD,a Rebiay Kıran MD,a Selma Salman MD,a Çiğdem Çağlayan MD,b
Aysun Şikar Aktürk MD,a Dilek Bayramgurler MD,a and Nilgün Bilen MDa
BACKGROUND: Nails, one of the most visible sites of body, are frequently involved in psoriasis and accepted as the most difficult site for topical treatment because of their anatomical structure. Healing of the psoriatic nails usually occurs when systemic therapy is initiated to treat severe skin psoriasis or joint involvement, but sometimes systemic therapy is essential for severe nail psoriasis, although Psoriasis Area and Severity Index (PASI) score is low or none of the joints are affected. In this case, knowing which systemic agent is most potent on nail findings is important.
AIM: We aimed to evaluate the effect of systemic antipsoriatic agents on nail findings.
METHODS: Eighty-seven psoriatis patients with fingernail involvement who required systemic treatment but had not used any systemic treatment in the previous 12 weeks were included in this study. Different systemic treatment agents were given to patients, considering factors such as age, sex, and joint involvement, but not nail involvement. The control group was recruited from psoriatis patients with nail involvement who were not receiving any systemic treatment. Baseline and week 16 Nail Psoriasis Severity Index (NAPSI) and PASI were detected in all groups. At the end of the study, effects of the agents on both PASI and NAPSI were compared statistically.
RESULTS: Patients were divided into 5 groups to receive either: 1) methotrexate, 2) narrow-band ultraviolet B phototherapy, 3) biological agents, 4) acitretin, or 5) no treatment (control group). None of the conventional treatment agents caused any significant difference on NAPSI at the end of week 16 compared with control group, although PASI decreased significantly. Rate of NAPSI changes were more prominent in the biological treatment group, and a statistically significant difference was detected when compared with the control group.
J Drugs Dermatol. 2013;12(9):1039-1043.
So Dug Lim MD PhD,a Un-Cheol Yeo MD PhD,b,c Il-Hwan Kim MD PhD,d
Chong Won Choi MD,cand Won-Serk Kim MD PhDc
BACKGROUND: Fractional Radiofrequency Microneedles (FRM) are minimally invasive devices that use inserting bipolar radiofrequency for deep dermal heating, has been introduced. We investigated the tissue response after FRM according to different energy levels in porcine skin.
METHODS: Porcine back skin was used in the study. A FRM device was composed of 49 insulated needles. Needles were vertically
inserted with 1.5mm depth and four different energy levels were used to examine wound healing response chronologically.
Histologic evaluation was done by hematoxylin & eosin (H&E) and heat shock proteins (HSP) 47 staining for immediately after, 2
days after, 14 days after, 28 days after and 10 weeks after the procedure. RT-PCR was done for various cytokines including HSP47,
HSP72, metalloproteinase (MMP), and extracellular matrix (ECM) proteins.
RESULTS: FRM treatment generated a thermally coagulated zone localized in the reticular dermis, without damaging the epidermis.
The coagulation necrosis zone in H&E staining was replaced by new collagen tissue over 10 weeks. RT-PCR studies revealed an
increase in HSP, MMPs, and ECM proteins. In the high energy level procedure, an increased number of fibroblasts were found.
CONCLUSION: FRM treatment induced a dermal remodeling process including neocollagenesis in the deep dermis. From this result,
FRM is expected to provide a good and positive efficacy for skin rejuvenation.
J Drugs Dermatol. 2013;12(9):1044-1049.