Improvement In Photodamage Research Articles

Assessment of reflectance confocal microscopy for monitoring treatment of actinic keratosis and field cancerization with daylight photodynamic therapy.

Actinic keratosis (AK) is the most common pre-malignant cutaneous lesion of the skin, often associated with field cancerization. Daylight photodynamic therapy (DL-PDT) is used as treatment, showing good histological results. Reflectance confocal microscopy (RCM) may be useful as a non-invasive, real-time approach to monitor treatment, however, there is a lack of data on the correlation between RCM and histopathological findings in AK patients treated with DL-PDT. To correlate histological and RCM findings and evaluate the efficacy of DL-PDT in patients with AK and field cancerization treated with DL-PDT. Patients with field cancerization and a minimum of six AK lesions on the face were included in the study. A single session combining methyl aminolevulinate followed by two-hour daylight exposure of the face was performed. RCM and biopsy were performed before and after three months of the intervention to compare efficacy between patients using the Wilcoxon test, and concordance of the findings based on the different methods was analysed using the Kappa test. Twenty-four patients completed the study. An improvement in photodamage and a decrease in the number of AK lesions (45.3% reduction) was observed. Regression in atypia and dysplasia was observed via histopathology and RCM, however, there was poor agreement between the methods. No changes were observed after treatment for inflammation, fibroplasia and acantholysis. Concordance between histological and RCM findings was poor, suggesting that RCM cannot replace the histopathological examination, however, it may be used as an adjuvant test for follow-up of patients. Despite this, DL-PDT proved to be an effective method for treating AK.

A Prospective, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Efficacy, Safety, and Patient Satisfaction of Tretinoin 0.05% Lotion for Chest Rejuvenation.

There is increasing interest in non-invasive options for chest rejuvenation with minimal to no downtime. Topical retinoids have long been used to correct photoaging due to their ability to promote epidermal hyperplasia, matrix metalloproteinase inhibition, collagen synthesis, and dispersion of melanin granules. Topical retinoid use is often limited by the ensuing irritation that occurs with initial use and resolves after about one month. Vehicle of delivery is a key factor to consider in order to minimize irritation and increase patient satisfaction. Micronized tretinoin 0.05% suspended in a polymer emulsion of hydrating ingredients (sodium hyaluronate, soluble collagen, and glycerin) is designed to aid in reducing irritation while ensuring uniform drug delivery. The primary objective of our study is to evaluate the safety, efficacy, and patient satisfaction of tretinoin 0.05% lotion for nonprocedural photorejuvenation of the chest. A total of 29 patients completed the trial, average age of 54.42 years (37-66 years old), Fitzpatrick II-IV skin types. Both the active and vehicle groups showed 30-40% improvement at day 180 according to the blinded evaluator mean percent improvement. Investigator global aesthetic improvement scale also trended towards improvement in both groups, with most patients exhibiting "improvement." Both the active and vehicle groups showed a significant change over time according to the nine-point photodamage and wrinkling scale, P<0.001 and P=0.007 (single factor ANOVA), respectively. The Fabi Bolton Wrinkle Scale also demonstrated improvement from screening to day 180; however, there was no statistical significance at any time point. At day 90, the active group had statistically significantly more erythema than the vehicle group (P<0.001), although both groups were only mild. At day 180, erythema decreased in both groups with the active group being similar to the vehicle group, 0.50±0.73 versus 0.09±0.30, respectively. Subjects in both the active and vehicle groups were equally satisfied at day 180, (2.38±1.15 in the active group versus 2.30±1.16 in the treatment group), with most subjects feeling "satisfied" with their results by day 180. This was also reflected in the subject global aesthetic improvement scale with most subjects noting noticeable improvement in the appearance of their chest from day 30 to day 180. Tretinoin 0.05% lotion delivered in a proprietary blend of hydrating ingredients offers a safe and efficacious option that has minimal downtime for patients seeking non-procedural photo-rejuvenation of the chest. The proprietary vehicle, containing hyaluronic acid, glycerin, and collagen, was crucial in minimizing irritation and producing at least a one-point improvement according to the 9 point photodamage scale and 30-40% improvement in photodamage as noted by the blinded evaluator percent improvement score in both the vehicle and active groups. J Drugs Dermatol. 2022;21(6):645-652. doi:10.36849/JDD.6658.

Open-label study assessing the efficacy and tolerability of topical skincare and sun protection products following intense pulsed light treatment.

The visible signs of photodamage can be improved by intense pulsed light (IPL). Active ingredients in cosmeceuticals also have effects on skin quality and pigmentation, and can camouflage post-treatment side effects. Combination therapies utilizing different treatment modalities have been shown to optimize clinical outcomes for skin rejuvenation and patient satisfaction. To evaluate the efficacy of a combination of IPL with a daily topical skincare and sunscreen regimen for the treatment of facial photodamage and for the improvement of IPL treatment tolerability. Twenty female subjects with moderate-to-severe facial photodamage, with past history of IPL treatments, received one IPL treatment followed by the use of the topical skincare regimen for 8weeks. An investigator assessed facial photodamage and hyperpigmentation at baseline, week 4, and week 8, and postprocedure erythema. Subject questionnaires were also administered at each visit. Compared to baseline, there was a significant improvement in photodamage and hyperpigmentation of bare facial skin. The application of the skincare regimen resulted in a significant reduction in post-IPL erythema, stinging/burning, and itching. The majority of patients were very satisfied or satisfied and felt the treatment regimen improved various aspects of skin quality and the tolerability of the procedure. The addition of a topical skincare regimen after IPL treatment to the face resulted in significant improvements in facial photodamage and pigmentation, decreased post-treatment side effects, and increased tolerability.

4-Hexyl-1,3-phenylenediol, a nuclear factor-κB inhibitor, improves photodamaged skin and clinical signs of ageing in a double-blinded, randomized controlled trial.

The nuclear factor-κB (NF-κB) pathway is a key mediator of inflammation; however, few studies have examined the direct effects of NF-κB inhibition on the skin. To investigate NF-κB activity in cultured human fibroblasts and to investigate the effects of 4-hexyl-1,3-phenylenediol (an NF-κB inhibitor) on elastin and collagen gene expression in vitro and on the clinical appearance of photodamaged skin. The amount and activity of NF-κB in human fibroblasts obtained from donors (17-78 years old) was measured after transfection with a NF-κB reporter and a luciferase promoter system. The expression of extracellular matrix (ECM) genes was determined using quantitative polymerase chain reaction. Women with moderate skin photodamage were randomized to daily treatment with a topical lotion containing 4-hexyl-1,3-phenylenediol (n = 30) or vehicle (n = 29) for 8 weeks, with clinical assessments at baseline and weeks 2, 4 and 8. Fibroblasts obtained from donors older than 50 years had higher NF-κB activity compared with cells from younger donors; inhibition of the NF-κB pathway with 4-hexyl-1,3-phenylenediol enhanced the expression of ECM genes. In women, treatment for 8 weeks with 4-hexyl-1,3-phenylenediol significantly improved crow's feet fine lines, cheek wrinkles, age spots, mottled pigmentation and radiance compared with both the vehicle and baseline. Furthermore, treatment with 4-hexyl-1,3-phenylenediol resulted in a twofold greater clinical improvement in overall photodamage compared with the vehicle group. Inhibition of the proinflammatory NF-κB pathway resulted in increased expression of ECM proteins in vitro and significant clinical improvement in photodamaged skin.

Daylight photodynamic therapy: The Southern California experience

Photodynamic therapy (PDT) is a safe and effective treatment for actinic keratoses (AKs) and photoactinic damage. Three elements are needed for PDT: a photosensitizer, oxygen, and a light source. Conventional PDT is performed with a variety of different laser and light sources including blue, yellow and red in addition to filtered intense pulsed lights (IPL). Daylight PDT, using ambient visible light has been reported as safe, time- and cost-efficient, and more comfortable than with other light sources. We report our experience with daylight PDT in 80 patients. Eighty patients with multiple actinic keratoses related to chronic photodamage underwent one or two sessions with daylight PDT. Anatomic locations treated included face, chest, arms, and legs. Aminolevulinic acid (ALA, Levulan, Kerastick Dusa USA) was applied one hour prior to light exposure. Thick actinic keratoses were gently curetted prior to ALA application. A chemical sunscreen was applied thirty minutes into the incubation and subsequently patients sat outside in the shade for 2.5 hours. The following day, patients applied a chemical sunscreen and went into either shaded or direct sunlight for 15-30 extra minutes depending on sensitivity. Significant pain associated with this second day exposure was an indication to return indoors immediately. After the second exposure they were instructed to stay inside for the remainder of the 48 hour post treatment period. All patients tolerated the procedure well. Patients denied any pain during the first two and half hour exposure. The second day exposure elicited a mild burning sensation that patients rated as a 2-3/10 though some patients elected to go outside protocol and 'tough it out' despite more significant discomfort. Patients and physicians noted significant reduction in photoactinic damage and actinic keratoses. Patients appreciated the convenience of the treatment. There were no significant adverse events, and no patients reported scarring. In this case series, daylight PDT achieved obvious improvement in photodamage, specifically precancerous lesions, and in photoaging with a reduction in lentigenes and other signs of aging. Patients reported significantly less pain than with conventional PDT and enjoyed the convenience of treatment generally in their backyard. It was noted to be a safe procedure with no significant adverse events such as scarring. Additionally, the cost of the procedure was significantly reduced, with ALA and its application being the only expenses.

Histologic improvement in photodamage after 12 months of treatment with tretinoin emollient cream (0.02%)

Topical retinoids, such as tretinoin, have been established as the gold standard for the treatment of photodamaged skin. This was a single-center, open-label, single-group, observational histologic subanalysis of 3 of 19 patients participating in a study of the efficacy and safety of tretinoin emollient cream 0.02% for the treatment of moderate to severe facial photodamage.Subjects were female, 18 years of age or older, and instructed to apply tretinoin 0.02% to the treatment areas for 12 months. Histology was undertaken using facial photographs and 2-mm biopsies of the lateral canthus area that were obtained from 3 subjects at baseline and 12 months.Histopathologic analyses revealed evidence of extensive solar elastosis at baseline for 2 of the 3 subjects who were white, with moderate elastosis observed for the third subject who was African American. Histologic improvements in photodamage following 12 months of treatment with tretinoin 0.02% were observed for each subject. Improvements included smoothing of the epidermis, a slightly thinner keratin layer, and thin, comparatively straight elastic and collagen fibers in the mid- to deep-dermal layer.The histologic changes in all subjects could be attributed to a remodeling (elastin) or repair (collagen) process that affected the connective tissue fibers in all layers of the dermis. These results suggest that tretinoin 0.02% may be an effective treatment for photodamage, and additional evaluation is warranted in future studies.

Combined superficial & deep fractional skin treatment for photodamaged skin—a prospective clinical trial

Background and objectives. Deep microthermal zones targeted by Fractional CO2 lasers stimulate fibroblast activity, whereas superficial microthermal zones target the epidermal layer pigment. The new combination modality enables targeting both deep and superficial disorders. The study is designed to evaluate the improvement in photodamage and determine downtime. Materials and methods. This IRB approved study was aimed to evaluate histology phenotype of combined deep and superficial skin resurfacing. A 120-micron, focused CO2 laser beam was used to create both deep and superficial fractional skin resurfacing using ultrapulse and continuous wave laser modes, respectively. Fifteen patients (skin types II–V) underwent combined treatment and returned for assessment at 1 week, 1 and 3 months to evaluate the clinical outcome. Additional histological analysis of human tissue was performed to elucidate the combined impact on tissue. Results. Pre-clinical histologies demonstrated the ability to achieve fractional discrete 1.3-mm-diameter spots of superficial ablation with a uniform shallow and narrow area of coagulation while maintaining the deep, fractional 120-micron-ablation spot capabilities. Histologies of the human tissue confirmed the ability to control both superficial and deep fractional treatment using a single handpiece. Pigmentation was greatly reduced at the 1 month follow-up with significant textural improvement. No unexpected AEs or SAEs were reported. Conclusion. The new modality enables combined superficial and deep fractional impact and improvements that are demonstrated at both the phenotype and tissue level.

Minimally ablative resurfacing with the confluent 2,790 nm erbium:YSGG Laser: A pilot study on safety and efficacy

The 2,790 nm Er:YSGG wavelength has a lower water absorption coefficient than the 2,940 nm Er:YAG, but a higher coefficient than the 10,600 nm CO(2) laser. This allows ablative resurfacing with mild thermal coagulation, which may increase clinical efficacy while reducing patient downtime. To evaluate the efficacy and safety of the confluent 2,790 nm Erbium:YSGG (Pearl™, Cutera) laser for facial rejuvenation. Eleven subjects (mean age 50, skin types I-III) with mild to moderate photodamage and wrinkles had two facial treatments with the 2,790 nm Er:YSGG laser using a fluence of 3.5 J/cm(2), pulse duration of 0.4 msecond, and 20% overlap. Treatments were performed 6 weeks apart. Pre-auricular biopsies from five subjects were evaluated at baseline and 6 weeks after the final treatment. Data from blinded photo assessments and subjects' self-assessment of improvement were analyzed 6 weeks after the final treatment. Additionally, long-term safety and efficacy were evaluated 2 years after the final treatment. Histologically, 80% of subjects had new collagen formation in the dermal grenz zone, and 60% had increased epidermal thickness. Almost all subjects (91%) showed improvement in tone/texture, 82% of subjects showed improvement in dyschromia and fine lines, and 54% showed improvement in wrinkles 6 weeks after the final treatment. Subjects' self assessment indicated "significant" to "dramatic" improvement in dyschromia (91% of subjects) and tone/texture (82%) 6 weeks after the final treatment. All subjects saw "mild" to "significant" improvement in fine lines and wrinkles. At the 2-year follow-up visit, 57% of the overall improvement achieved at 6 weeks was maintained. No adverse events were reported throughout the study. Ablative resurfacing with the 2,790 nm Er:YSGG laser demonstrated visible improvement in photodamage with good tolerability and minimal downtime. Subjects were highly satisfied, especially with respect to dyschromia, skin tone, and texture.

The Effect of Increasing Fluence on the Treatment of Actinic Keratosis and Photodamage by Photodynamic Therapy with 5-Aminolevulinic Acid and Intense Pulsed Light

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) and intense pulsed light (IPL) is a relatively new combination for the treatment of actinic keratosis (AK) and photodamage. The objective of this study was to determine the effect of increasing the fluence of IPL on the outcome of patients with these skin conditions. Patients (N = 24) were randomly assigned to five treatment treatment groups: control (IPL alone) and ALA with 20, 25, 40, and 50 J/cm(2) fluence of IPL. Each patient received a single treatment. ALA was applied twice and allowed to incubate 2 h before IPL irradiation. Results were evaluated 5-7 days and 8 weeks after treatment. Clearance of AK lesions was evaluated by counting lesions before and after treatment, and improvement in photodamage was assessed by comparing pre- and post-treatment photographs. Statistical evaluation was based at nonparametric tests with a cut-off level at p < 0.10 and a confidence interval at 95%. Responses to treatment were greatest in patients who received ALA and IPL fluences of 40 and 50 J/cm(2). Responses were "marked" in 19% of the patients receiving 50 J and "moderate" in 19% of the patients receiving 40 J. Compared to the mean pre-treatment AK grades, the mean post-treatment grades were 56% lower in the 50 J treatment group, 32% lower in the 25 J group, 50% lower in the 40 J group, 20% lower in the 20 J group, and 7% lower in the control group. Erythema, edema, crusts and erosion, and pain did not cause any patient to discontinue the study. AK clearance, but not photorejuvenation, appears to improve with increasing fluence at the ALA PDT-IPL levels used in this study without serious adverse effects.

1,927-nm Fractional Thulium Fiber Laser for the Treatment of Nonfacial Photodamage: A Pilot Study

A 1,927-nm wavelength was recently added to the 1,550-nm erbium-doped fiber laser. This wavelength possesses a higher absorption coefficient for water than the 1,550-nm, conferring greater ability to target epidermal processes. To evaluate the efficacy and safety of a novel 1,927-nm fractional thulium fiber laser in the treatment of nonfacial photodamage. Nine participants with nonfacial photodamage underwent three laser treatments (at 3- to 4-week intervals) at pulse energies of 10 to 20 mJ and 30% to 55% surface area coverage (4-8 passes) with a 1,927-nm thulium fiber laser. A blinded assessor and participants evaluated clinical improvement of treatment areas at 1-month follow-up using a quartile grading scale (0-4). Nine participants with a total of 12 treatment areas completed three treatments and the 1-month follow-up visit. At follow-up, a blinded assessor rated mean improvement in photodamage as 3.25 ± 1.0 and lentigines as 3.33 ± 0.9 on a scale of 0 to 4 (0=none, 1=1-25%, 2=26-50%, 3=51-75%, and 4=76-100% improvement). Skin responses observed after treatment were moderate erythema, mild edema, itching, and desquamation. No scarring or postinflammatory hyper- or hypopigmentation was observed. The 1,927-nm fractional thulium fiber laser is a safe, effective treatment for nonfacial photodamage. Dr. Polder is a principal investigator and Dr. Suzanne Bruce is a consultant for Solta Medical.

Efficacy of a new fractional CO2 laser in the treatment of photodamage and acne scarring

This study evaluates the efficacy and safety of a novel fractional CO(2) laser device for improving facial rhytids, hyperpigmentation, enlarged pores, skin laxity, and acne scarring. Subjects (n= 15) were treated three to five times at 3-week intervals. Biopsy specimens were used to evaluate healing response and neocollagenesis. Clinical improvement was rated on a quartile rating scale from digital photographs. Subject discomfort during treatment was evaluated on a scale of 0 to 5. Fourteen subjects who completed the study achieved good to excellent improvement in overall appearance, with 60% rated excellent. Improvement in photodamage was good to excellent in 92% of subjects, and reduction in rhytids was good to excellent in 85%. A total of 79% of subjects achieved good to excellent improvement in pore sizes and skin laxity. Subject discomfort during treatment was 3.0 +/- 0.7. Erythema persisted for 2-3 days, and subjects resumed normal activities 1-2 days after the procedure. Histological slides after a single treatment showed new collagen formation. The SmartSkin fractional CO(2) system (Cynosure, Inc., Westford, MA, USA) provides significant improvement for the treatment of facial wrinkles, hyperpigmentation, pore size, and skin laxity associated with photodamage.

The clinical efficacy of topical methyl-aminolevulinate photodynamic therapy in moderate to severe actinic keratoses of the face and scalp

Introduction: Since actinic keratoses (AKs) often appear in areas with field cancerization, photodynamic therapy (PDT) may have significant advantages over the standard treatment options. Objectives: Clinical efficacy of PDT with topical methyl aminolevulinate (MAL-PDT) in field cancerization was evaluated with respect to the number of AKs and photodamage. Methods: A total of 14 patients with 223 AKs on the face or scalp were treated with MAL-PDT. Two treatments with a 3-monthly interval were given. At baseline, before the second treatment and 3 months after the end of therapy, the number of AKs were counted and photodamage was assessed with respect to skin roughness, hyperpigmentation, hypopigmentation, scarring, atrophy, telangiectasia and wrinkling. Results: Complete clearance was reached in patients with a moderate degree of actinic damage, whereas a severe degree of field cancerization demonstrated only partial clearance. The global score for photodamage improved significantly. After the follow-up period, none of the patients reaching clearance had developed relapsing or new AKs. Conclusions: MAL-PDT induces a high clearance rate of AKs, dependent on the degree of field cancerization, with a good improvement in photodamage and prevention of developing new AKs. Thus, more PDT sessions are needed in patients with a severe degree of field cancerization.

Fractional Photothermolysis: A Review and Update

Fractional resurfacing is a new laser treatment modality that creates numerous microscopic thermal injury zones of controlled width, depth, and density that are surrounded by a reservoir of spared epidermal and dermal tissue, allowing for rapid repair of laser-induced thermal injury. This unique modality, if implemented with proper laser-delivery systems, enables high-energy treatments while minimizing risks. In this article, we review the various fractional laser devices, including the new fractional ablative devices, as well as the results of studies on the clinical efficacy of fractional photothermolysis. This technology offers patients significant clinical improvement in photodamage, melasma, and scarring with modest treatment-related downtime and minimal risk of complications.

Fractional Photothermolysis: Treatment of Facial and Nonfacial Cutaneous Photodamage with a 1,550-nm Erbium-Doped Fiber Laser

To evaluate the safety and effectiveness of a novel nonablative 1,550 nm erbium-doped fiber laser in the treatment of facial and non-facial photodamaged skin. 50 patients with mild to moderate cutaneous photodamage, rhytides, and dyspigmentation received 3 successive treatments at 3-4 week intervals with a 1,550 nm erbium-doped fiber laser (Fraxel, Reliant Technologies Inc., San Diego, CA). Clinical improvement of treatment areas was independently determined by two masked assessors' evaluations of comparative photographs at baseline and 3, 6, and 9 months post-treatment using a quartile grading scale. Patient satisfaction surveys were also obtained at each follow-up visit. Mean clinical improvement at 3 months for the face was 2.23 and 1.85 for non-facial skin (p<0.001). Mean improvement at 6 months was 2.10 for the face and 1.81 for non-facial skin (p<0.001). Mean improvement at 9 months was 1.96 for the face and 1.70 for non-facial skin (p<0.001). At least 51% to 75% improvement in photodamage at the 9-month follow-up was achieved in 73 and 55% of facial and non-facial treated skin, respectively. Side effects were limited to transient erythema and edema in the majority of patients. No prolonged pigmentary changes or scarring were observed. Patient satisfaction surveys mirrored the observed clinical effects. The nonablative 1,550 nm erbium-doped fiber laser is an effective treatment for facial and non-facial photodamage, rhytides, and dyspigmentation with a favorable recovery and side effect profile.

Clinical efficacy assessment in photodamaged skin of 0.5% and 1.0% idebenone

Idebenone is an antioxidant lower molecular weight analogue of coenzyme Q10. Previously, idebenone was shown to be a very effective antioxidant in its ability to protect against cell damage from oxidative stress in a variety of biochemical, cell biological, and in vivo methods, including its ability to suppress sunburn cell (SBC) formation in living skin. However, no clinical studies have been previously conducted to establish the efficacy of idebenone in a topical skincare formulation for the treatment of photodamaged skin. In this nonvehicle control study, 0.5% and 1.0% idebenone commercial formulations were evaluated in a clinical trial for topical safety and efficacy in photodamaged skin. Forty-one female subjects, aged 30-65, with moderate photodamaged skin were randomized to use a blind labelled (either 0.5% or 1.0% idebenone in otherwise identical lotion bases) skincare preparation twice daily for six weeks. Blinded expert grader assessments for skin roughness/dryness, fine lines/wrinkles, and global improvement in photodamage were performed at baseline, three weeks and six weeks. Electrical conductance readings for skin surface hydration and 35 mm digital photography were made at baseline after six weeks. Punch biopsies were taken from randomly selected subjects, baseline and after six weeks, and stained for certain antibodies (interleukin IL-6, interleukin IL-1b, matrixmetalloproteinase MMP-1, collagen I) using immunofluorescence microscopy. After six weeks' use of the 1.0% idebenone formula, a 26% reduction in skin roughness/dryness was observed, a 37% increase in skin hydration, a 29% reduction in fine lines/wrinkles, and a 33% improvement in overall global assessment of photodamaged skin. For the 0.5% idebenone formulation, a 23% reduction in skin roughness/dryness was observed, a 37% increase in skin hydration, a 27% reduction in fine lines/wrinkles, and a 30% improvement in overall global assessment of photodamaged skin. The immunofluorescence staining revealed a decrease in IL-1b, IL-6, and MMP-1 and an increase in collagen I for both concentrations.

Sustained improvement in photodamaged skin with reduced tretinoin emollient cream treatment regimen: Effect of once-weekly and three-times-weekly applications

Background: Previous studies have documented reversal of long-term photodamage with once-daily applications of topical tretinoin. Objective: Our purpose was to assess the effectiveness of tretinoin emollient cream in maintaining improvement in photodamage with a reduced frequency of applications. Methods: A total of 126 subjects who completed 48 weeks of once-daily treatment with tretinoin emollient cream 0.05% were enrolled for an additional 24 weeks of tretinoin once weekly, three times weekly, or no therapy. Results: The clinical improvement observed during 48 weeks of once-daily treatment was sustained with three-times weekly applications and to a lesser extent with once-weekly dosing, whereas effects tended to regress in subjects off therapy. The overall incidence of adverse events in the skin and subcutaneous tissues appeared to vary with dose frequency. Conclusion: After 48 weeks of once-daily treatment, the continued use of tretinoin emollient cream 0.05% at a dose of three times per week maintains and, in some cases, may further enhance improvement in photodamage. Discontinuation of therapy results in some reversal of beneficial effects. (J Am Acad Dermatol 1997;37:227-30.)