Topical kinetin 0.1% lotion for improving the signs and symptoms of rosacea.

Many patients with rosacea are unable to tolerate extended treatment periods with topical agents because of the unusually high skin sensitivity that often accompanies rosacea. Kinetin (N(6)-furfuryladenine) is a plant cytokinin that reportedly helps restore skin barrier function and may be useful to ameliorate the signs and symptoms of rosacea. The purpose of this open-label study was to determine the tolerance and efficacy of twice-daily application of kinetin 0.1% lotion for improving the signs and symptoms of mild to moderate facial rosacea. Subjects applied kinetin 0.1% lotion twice daily to the face, with daily use of a sunscreen of sun protection factor 30. Subjects were evaluated at baseline and at 4-week intervals for 12 weeks to assess efficacy and tolerance. Results of this study suggest that kinetin 0.1% lotion is a well-tolerated moisturizing lotion option for subjects with mild to moderate inflammatory rosacea.

'Keratolytic' properties of benzoyl peroxide and retinoic acid resemble salicylic acid in man.

OBJECTIVES: Retinoic acid (RA) and benzoyl peroxide (BP) were studied, comparing their keratolytic efficacy and water barrier disruption to that of salicylic acid (SA), a well-established keratolytic, under similar conditions. PATIENTS/METHODS: Six volunteers were included in this blinded study. Eleven randomized test sites were marked on the volar forearms, containing sites for untreated skin at time zero, unoccluded, occlusion, and vehicle controls for 3 and 6 h, and each of BP, RA, and SA solutions for 3 and 6 h. At each time point, occlusion at 5 of the test sites was removed, and chromameter measurements were performed over 30 min. Each site then underwent 25 stratum corneum (SC) tape strippings. At 1, 5, and 30 min after the last stripping at each site, TEWL measurements were performed. Quantitative protein analysis of the SC from the tapes was then performed. RESULTS AND CONCLUSION: after 3 h, bp was significantly more effective in disrupting sc cohesion than sa and ra, indicating bp is a moderate keratolytic agent in addition to its antimicrobial properties. After 6 h, all three agents were similarly effective in keratolysis. Barrier disruption, as measured by TEWL, paralleled depth of SC removal. SA tended to exhibit the greatest keratolytic efficacy superficially, hence its clinical effectiveness in superficial conditions such as comedonal acne, whereas BP was more effective at deeper levels, complimenting its antimicrobial effects and enabling it to treat deeper, more inflammatory lesions. None of the agents significantly affected skin erythema. These techniques provide a robust and rapid assay for in vivo keratolytic demonstration.

Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks.

OBJECTIVE: To assess the safety and efficacy of 4 concentrations of tazarotene cream in the treatment of facial photodamage. DESIGN: Prospective weekly multicenter, investigator-masked, randomized, parallel-group study. SETTING: University hospitals and clinical research centers. PATIENTS: Three hundred forty-nine subjects with facial photodamage. INTERVENTION: Daily topical application of tazarotene cream (0.01%, 0.025%, 0.05%, and 0.1%) compared with its vehicle and with 0.05% tretinoin emollient cream. RESULTS: Tazarotene cream and tretinoin cream significantly improved mottled hyperpigmentation and fine wrinkles. At week 24, treatment success rates based on global responses were 67% (39 of 58 subjects) with 0.1% tazarotene, 52% (30 of 58 subjects) with 0.05% tazarotene, 36% (21 of 58 subjects) with 0.025% tazarotene, 41% (24 of 59 subjects) with 0.01% tazarotene, 55% (32 of 58 subjects) with 0.05% tretinoin, and 22% (13 of 58 subjects) with vehicle. Local adverse events, although more frequent with tazarotene at higher concentrations, were generally mild to moderate. CONCLUSIONS: Tazarotene in a cream formulation is safe and is associated with positive changes in the treatment of photodamaged facial skin.

Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light.

BACKGROUND: Aminolevulinic acid hydrochloride (ALA, Levulan) applied topically to actinic keratoses (AKs) leads to accumulation of the photosensitizer protoporphyrin IX, which, when activated by exposure to light, eradicates AKs. OBJECTIVE: We examined the safety and efficacy of photodynamic therapy using topical 20% ALA in a solution formulation and varying blue light doses to treat multiple AKs on the face and scalp. METHOD: This is a multicenter, investigator-blinded, randomized, vehicle-controlled study. RESULTS: Thirty-six patients with clinically typical AKs were treated with 20% ALA; 14 to 18 hours later, they were irradiated with a nonlaser fluorescent blue light source. With the optimal light dose of 10 J/cm(2), 88% of the AKs completely cleared 8 weeks after a single photodynamic treatment, compared with 6% after treatment with vehicle and light. CONCLUSION: Topical ALA PDT using a nonlaser, blue light source is an effective treatment for multiple AKs.

Two considerations for patients with psoriasis and their clinicians: what defines mild, moderate, and severe psoriasis? What constitutes a clinically significant improvement when treating psoriasis?

The definitions of psoriasis severity and clinically significant improvement in psoriasis are used to classify treatments, obtain Food and Drug Administration approval, and determine product labeling and reimbursement. The Medical Advisory Board of the National Psoriasis Foundation has addressed these issues because of their importance in the clinical trials that are conducted to gain FDA approval of indications. Narrow indications, which are without a sound rational basis, will-in this era of constant oversight by third party payers-affect physicians' ability to manage patients with psoriasis. Body surface area (BSA) is usually used to define severity for clinical trials. It is not optimal for defining psoriasis severity because there are some patients with low BSA involvement who have very severe psoriasis and some patients with high BSA involvement who have mild psoriasis. We conclude that a quality of life (QOL) standard is better than BSA measurement for identifying patients with severe psoriasis. The second issue is what defines clinically significant improvement for patients with psoriasis. Setting an arbitrarily high criterion of clinical efficacy for new psoriasis treatments will likely limit the development and approval of useful treatments. To maximize the availability of useful psoriasis treatments, it is our thesis that psoriasis treatments should be approved when they have been shown to produce a statistically significant level of improvement in well-designed clinical trials.

Psoriasis: current perspectives with an emphasis on treatment.

An individualized treatment regimen is necessary for each patient with psoriasis because of the diverse nature of the disease. The manifestation of psoriasis, the severity and extent of the lesions, and the medical history and lifestyle of the patient are important factors that determine the selection of treatment, but in general therapies with the fewest side effects are preferred. First-line topical treatments are corticosteroids, calcipotriene, and tazarotene. If topical treatments are unsuccessful, phototherapy with ultraviolet B or photochemotherapy with psoralens plus ultraviolet A (PUVA) are the next choices. If psoriasis fails to respond to an adequate trial of topical therapy or phototherapy, systemic therapies including methotrexate, acitretin, or cyclosporin should be initiated. Because the regimens involved in systemic and phototherapy are complex and require frequent dose adjustments and specialized equipment, the patient should be referred to a dermatologist when topical therapy is not effective.

The management of psoriasis-tazarotene: the bottom line.

In treating patients with psoriasis, my frustration has been in the topical therapy of patients with limited or mild psoriasis. When clinical improvement was obtained with topical therapy, it could not be maintained. Clinical experience has shown that, in the minority of patients with moderate to severe psoriasis, we can generally do a much better job not only improving, but also maintaining improvement over the course of a year by using therapeutic options such as psoralen/ultraviolet A, ultraviolet B, methotrexate, or etretinate. In a survey that we did several years ago, dermatologists registered with the American Academy of Dermatology reported that approximately 80% of their patients with psoriasis had limited disease requiring only topical therapy, while the remaining 20% had more extensive disease requiring photo or systemic therapies. Thus the challenge has been to improve our ability to better treat limited disease.

Tazarotene 0.1% gel plus corticosteroid cream in the treatment of plaque psoriasis.

BACKGROUND: Topical corticosteroids are often used in the treatment of psoriasis, but long-term use may be associated with serious adverse events such as tachyphylaxis or atrophy of the skin. Tazarotene, a new topical retinoid, has demonstrated significant clinical benefits but can cause mild to moderate local irritation. OBJECTIVE: We evaluate whether a combination treatment of topical tazarotene and a topical corticosteroid would increase efficacy while reducing the incidence of local adverse events associated with a topical retinoid. METHODS: Three hundred patients enrolled in an investigator-masked study were randomly assigned to 1 of 4 treatment groups: tazarotene 0.1% gel in combination with placebo cream, or with a low-, mid-, or high-potency corticosteroid cream, for 12 weeks of treatment and a posttreatment follow-up at week 16. RESULTS: Tazarotene 0.1% gel in combination with a mid- or high-potency corticosteroid, when compared with tazarotene plus placebo cream, achieved significantly greater reductions in scaling, erythema, and overall lesional severity, and a decreased incidence of adverse events. CONCLUSION: All tazarotene combinations (including tazarotene plus placebo) were highly effective in rapidly reducing the severity of psoriasis. Combining tazarotene with a topical corticosteroid increased efficacy while reducing the incidence of local adverse events.

Consensus workshop on the toxic effects of long-term PUVA therapy.

The possibility that there is an increased risk of melanoma in patients with psoriasis treated with psoralen-UV-A (PUVA) therapy has raised concern on the part of physicians and patients about the long-term safety of this treatment. In response to this concern, the National Psoriasis Foundation sponsored a workshop at which invited participants with expertise in PUVA therapy, psoriasis treatment, melanoma and nonmelanoma skin cancer, and epidemiological and clinical trials were asked to develop a consensus on the following 3 issues: the risk of long-term adverse effects of PUVA therapy with emphasis on nonmelanoma and melanoma skin cancer; the guidelines for physicians and patients for selection and use of PUVA therapy with consideration of the risk-benefit ratio of this treatment compared with the risk-benefit ratios of alternative treatments; and the directions for further evaluation of the long-term effects Of PUVA therapy.

Once-weekly fluconazole (450 mg) for 4, 6, or 9 months of treatment for distal subungual onychomycosis of the toenail.

BACKGROUND: Fluconazole is a bis-triazole antifungal agent approved for the treatment of oropharyngeal, esophageal, and vaginal candidiasis, serious systemic candidal infections, and cryptococcal meningitis. OBJECTIVE: The purpose of this study was to evaluate three different durations of once-weekly fluconazole for the treatment of onychomycosis of the toenail caused by dermatophytes. METHODS: In a multicenter, randomized, double-blind, parallel, placebo-controlled trial, 384 patients with distal subungual onychomycosis of the toenail received fluconazole, 450 mg once weekly, or placebo for 4, 6, or 9 months. For inclusion, patients were required to have mycologically confirmed distal subungual onychomycosis of the toenail with a large toenail at least 25% clinically affected but having at least 2 mm of healthy nail between the nail fold and the proximal onychomycotic border. Efficacy was assessed by clinical and mycologic (microscopic and microbiologic) measures at screening, at every treatment visit starting at month 3, and at months 2, 4, and 6 after therapy. Observed or volunteered adverse events were recorded and classified at all visits. RESULTS: At the end of treatment, very significantly superior clinical and mycologic results were achieved in all fluconazole groups compared with placebo (p=0.0001). This superiority was largely maintained over 6 months of follow-up. The clinical and mycologic responses of the 9-month treatment duration were significantly superior to the 4- and 6-month durations. Similar percentages of patients in the fluconazole and placebo groups reported adverse experiences for all three durations of the study. CONCLUSION: Results of this study support the efficacy and safety of fluconazole in the treatment of distal subungual onychomycosis of the toenail.

The safety and efficacy of tazarotene gel, a topical acetylenic retinoid, in the treatment of psoriasis.

OBJECTIVE: To determine the safety and efficacy of topically applied tazarotene gel in the treatment of mild to moderate psoriatic plaques. DESIGN: Two multicenter, double-blind, randomized studies of 6- and 8-week duration, with an 8-week follow-up in the second study. SETTING: Medical center outpatient dermatology services. PARTICIPANTS: One hundred fifty-three adults with 2 bilateral target plaques on the trunk, legs, or arms. INTERVENTIONS: Vehicle gel or 0.01% and 0.05% tazarotene gel administered twice daily to 45 patients (study A), or 0.05% and 0.1% tazarotene gel administered either once or twice daily to 108 patients (study B). MAIN OUTCOME MEASURES: Treatment success and plaque elevation, scaling, and erythema vs time. RESULTS: The 0.01% tazarotene gel showed minimal efficacy. Applications of 0.05% and 0.1% tazarotene gels administered once or twice daily, resulted in significant improvements in plaque elevation, scaling, erythema, and overall clinical severity as early as 1 week. Treatment success rates (defined as > 75% improvement from baseline) were 45% with 0.05% tazarotene gel vs 13% with vehicle gel after 6 weeks of treatment (P < .05; study A) and ranged from 48% to 63% with the various tazarotene treatment regimens after 8 weeks of treatment (study B). These improvements were evident at the 8-week follow-up. Treatment-related adverse effects were generally limited to mild or moderate local irritation and were less frequent with the treatment regimen administered once daily. CONCLUSION: The 0.05% and 0.1% tazarotene gels demonstrated significant efficacy in the treatment of mild to moderate psoriatic plaques that persisted after cessation of treatment.

Tazarotene gel: efficacy and safety in plaque psoriasis.

Tazarotene is the first of a new generation of acetylenic retinoids developed for the topical treatment of mild-to-moderate plaque psoriasis. Controlled clinical trials have demonstrated that once-daily tazarotene 0.05% and 0.1% gels are effective in improving and reducing clinical signs and symptoms of psoriasis on trunk and limb lesions and difficult-to-treat elbow and knee plaques. Tazarotene has a rapid onset of action indicated by significant improvements as early as the first week of treatment. Sustained beneficial effects have been observed in some patients for up to 12 weeks after the cessation of therapy. Compared with twice-daily fluocinonide 0.05% cream, once-daily tazarotene 0.05%, and 0.1% gels were similarly effective in reducing plaque elevation. Once-daily tazarotene 0.05% and 0.1% gels demonstrated a more prolonged therapeutic effect after discontinuation than twice-daily fluocinonide cream. Tazarotene is generally well tolerated, with adverse events limited to local irritation. Tazarotene appears to be an effective addition to the currently available treatments for plaque psoriasis.

Tretinoin emollient cream for photodamaged skin: results of 48-week, multicenter, double-blind studies.

BACKGROUND: The ability of topical tretinoin to improve certain signs of skin photodamage has been shown previously. OBJECTIVE: Our purpose was to assess the effectiveness of tretinoin emollient cream in maintaining or further improving photodamaged skin during extended use. METHODS: Photodamaged subjects who completed 24 weeks of once-daily use of tretinoin emollient cream 0.05% (n = 149) or 0.01% (n = 149) continued to use the same strength formulation in a 24-week double-blind extension. RESULTS: Maintenance of improvement or continued reduction in signs of photodamage was noted in both investigators' and subjects' evaluations of the 0.05% and 0.01% preparations; these results were confirmed by skin replica analyses. Cutaneous side effects were less common during the extension study than during the first 24 weeks of therapy. CONCLUSION: Both strengths of tretinoin emollient cream (0.05% and 0.01%) appeared safe and effective in the treatment of photodamaged skin during a 48-week treatment period.

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.

Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect.

BACKGROUND: Topical therapy providing initial improvement and maintenance of effect after treatment of the large majority of patients with limited, mild to moderate psoriasis is not presently available. Previous topical retinoids have generally been either ineffective or too irritating for therapy of psoriasis. OBJECTIVE: Our purpose was to evaluate a new topical retinoid, tazarotene, in the treatment of stable plaque psoriasis during treatment and posttreatment periods. METHODS: In a double-blind manner, 324 patients were randomly selected to receive tazarotene 0.1% or 0.05% gel, or vehicle control, once daily for 12 weeks and were then followed up for 12 weeks after treatment. RESULTS: Of the total, 318 patients could be evaluated. Tazarotene gels were superior (p < 0.05) to vehicle, often as early as treatment week 1, in all efficacy measures: plaque elevation, scaling, and erythema; treatment response; percentage treatment success (patients with > or = 50% improvement); and time to initial success. Efficacy was equivalent on target lesion sites (trunk or limbs and knees or elbows) and overall. A sustained therapeutic effect was observed for 12 weeks after treatment. Tazarotene gel was cosmetically acceptable. There was low systemic absorption, limiting toxicity to local irritation. CONCLUSION: Once-daily tazarotene was effective and safe as a topical monotherapy for plaque psoriasis, providing rapid reduction of signs and symptoms.

Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid. A pilot dose-ranging study.

OBJECTIVE: To examine the safety and efficacy of photodynamic therapy using topical 5-aminolevulinic acid (ALA) and red light to treat actinic keratoses (AKs). DESIGN: Actinic keratoses were treated with topical ALA (concentrations of 0%, 10%, 20%, or 30%) under occlusion for 3 hours. Before photodynamic therapy, sites were examined for fluorescence. Sites were irradiated with an argon pumped dye laser (630 nm) at fluences of 10 to 150 J/cm2. SETTING: Academic medical center. PATIENTS: Forty patients with 6 clinically typical, previously untreated AKs per patient. MAIN OUTCOME MEASURE: Complete resolution and decrease in lesion area of the AK relative to baseline evaluated at weeks 1, 4, 8, and 16. RESULTS: Three hours after ALA administration, lesions showed moderate red fluorescence. Cutaneous phototoxic effects, localized erythema and edema, peaked at 72 hours. Patients experienced mild burning and stinging during light exposure. Eight weeks after a single treatment using 30% ALA, there was total clearing of 91% of lesions on the face and scalp and 45% of lesions, on the trunk and extremities. No significant differences were observed in clinical responses with treatment using 10%, 20%, or 30% ALA. All concentrations of ALA were more effective than treating AKs with vehicle and light. CONCLUSIONS: Topical photodynamic therapy with ALA is an effective treatment of typical AKs. Complete clearing of nonhypertrophic AKs can be achieved with 10%, 20%, or 30% ALA that is easily tolerated by the patient. Lesions on the face and scalp are more effectively treated than lesions on the trunk and extremities. Hypertrophic AKs did not respond effectively.

Safety, efficacy and duration of therapeutic effect of tazarotene used in the treatment of plaque psoriasis.

Topical therapies are first-line treatment for mild/limited stable plaque psoriasis. Disadvantages of currently available therapies include lack of short-term efficacy and long-term maintenance, adverse effects, and cosmetic problems. Tazarotene is a new topical retinoid which has proven to be efficacious in the treatment of mild-to-moderate plaque psoriasis. Results from a large, multicentre, pivotal study show that a once-daily application is as effective as a first-line monotherapy, providing rapid resolution of signs and symptoms and sustained therapeutic effects in some patients. Tazarotene gel is cosmetically acceptable, and is minimally absorbed systemically, with adverse events limited to local irritation.