Efficacy of micronutrient supplementation on skin aging and seasonal variation: a randomized, placebo-controlled, double-blind study.

BACKGROUND: Several studies have confirmed dramatic changes in skin surface parameters during the winter months. Although there are many studies supporting the positive effects of topical treatment, there are no published studies demonstrating the effects of oral supplementation in the prevention of negative skin changes during winter. The purpose of this study was to evaluate the efficacy of an oral micronutrient supplement in preventing the negative effects of winter weather on skin quality using noninvasive biometrologic instruments. METHODS: This study included 80 healthy female volunteers aged 35-55 years with phototype II-IV skin. Randomization was balanced. Two tablets of a micronutrient supplement (Perfectil® Platinum) or placebo were administered once daily for 4 months. The volunteers were examined at baseline, after 4 months, and 6 weeks after termination of treatment (month 5.5). The evaluation included skin microrelief by Visioscan® as the main outcome, and the secondary outcomes were results on standard macrophotography, skin tension by Reviscometer®, skin high-frequency ultrasound, and self-assessment. RESULTS: For all pseudoroughness and microrelief indicators, there was a significant increase from baseline to month 4 in the placebo group (P<0.05) but no change in the active group. Descriptive statistics for the mean minimum, mean maximum, and minimum to maximum ratio on the nonexposed study zone showed a significant and dramatic difference between baseline and month 4 and between baseline and month 5.5 (P<0.05) in the active group, indicating decreasing anisotropy of the skin. High-frequency ultrasound on the exposed study zone revealed that skin thickness was significantly decreased in the placebo group during winter but was stable in the treated group (P<0.01). The photography scaling and self-assessment questionnaire revealed no significant changes in either group. CONCLUSION: These results indicate that the skin is prone to seasonal changes during winter, particularly in exposed areas. The data also indicate that oral supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin.

The efficacy of afamelanotide and narrowband UV-B phototherapy for repigmentation of vitiligo.

BACKGROUND: Vitiligo is characterized by depigmented patches of skin due to loss of cutaneous melanocytes. Many recent studies have demonstrated defects in the melanocortin system in patients with vitiligo, including decreased circulating and lesional skin levels of α-melanocyte-stimulating hormone (α-MSH). Afamelanotide is a potent and longer-lasting synthetic analogue of naturally occurring α-MSH. OBSERVATIONS: We describe the preliminary results of 4 patients with generalized vitiligo who developed repigmentation using afamelanotide in combination with narrowband UV-B (NB-UV-B) phototherapy. Patients were treated 3 times weekly with NB-UV-B and starting in the second month received a series of 4 monthly implants containing 16 mg of afamelanotide. Afamelanotide induced faster and deeper repigmentation in each case. All patients experienced follicular and confluent areas of repigmentation within 2 days to 4 weeks after the initial implant, which progressed significantly throughout treatment. All patients experienced diffuse hyperpigmentation. CONCLUSIONS: We propose that afamelanotide represents a novel and potentially effective treatment for vitiligo. The combined therapy of NB-UV-B and afamelanotide appears to promote melanoblast differentiation, proliferation, and eumelanogenesis. Further studies are necessary to confirm these observations.

In vivo reflectance confocal microscopy of the skin: a noninvasive means of assessing body cystine accumulation in infantile cystinosis.

BACKGROUND: Patients with infantile nephropathic cystinosis have progressive accumulation of cystine in tissues leading to delayed extrarenal complications. No simple tool is available to evaluate the level of body cystine accumulation. OBJECTIVE: We sought to determine the value of in vivo reflectance confocal microscopy of the skin in patients with infantile nephrogenic cystinosis. METHODS: Nine patients and control subjects were recruited for this study. Images were acquired by means of a near-infrared reflectance confocal laser scanning microscope. RESULTS: Scattered bright particles within the papillary dermis were observed in all patients but not in control subjects. The density of particles ranged from numerous (+++) to very few (+/-) and their distribution was heterogeneous. Electron microscopy confirmed that these particles corresponded to cystine crystal deposits within dermal fibroblasts. The density of cystine crystals within the dermis was greater in older patients, in patients with a high leukocyte cystine concentration, and with delayed cysteamine therapy. There was no correlation between the density of cystine deposits and renal disease or hypopigmentation but high levels of deposition occurred in association with extrarenal manifestations. LIMITATIONS: This is a preliminary study on a small sample of patients. Repeated examination and longer follow-up is necessary. CONCLUSION: In vivo reflectance confocal microscopy of the skin appears to be a noninvasive means of assessing body cystine accumulation in infantile cystinosis and could be used as a complementary marker of treatment response in addition to leukocyte cystine measurement.

Signalling and chemosensitivity assays in melanoma: is mutated status a prerequisite for targeted therapy?

Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MAPK pathway was activated and a significant response to sorafenib, a mitogen-activated protein kinase (MAPK)/RAF inhibitor, was found in signalling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months, with marked necrosis in some lesions. Chemosensitivity assays and signalling pathway studies could be of great value in addition to genotyping for assessing the most appropriate treatment in melanoma.

Efficacy and Safety of Efalizumab in Patients with Moderate-to-Severe Plaque Psoriasis Resistant to Previous Anti-Psoriatic Treatment: Results of a Multicentre, Open-label, Phase IIIb/IV Trial.

OBJECTIVES: To evaluate the efficacy and safety of efalizumab in continuous or interrupted therapy of adults with moderate-to-severe plaque psoriasis who had failed to respond to or were intolerant of other systemic therapies, including methotrexate, ciclosporin and psoralen plus UVA phototherapy, or for whom such therapies were contraindicated. METHODS: Patients received a conditioning dose of efalizumab 0.7 mg/kg followed by once-weekly open-label efalizumab 1.0 mg/kg for 11 weeks. Responders (Physician Global Assessment [PGA] score of "good" or better at Week 12) could continue efalizumab for a further 8 weeks (continuous-treatment period). Nonresponders transitioned to alternative anti-psoriasis medication or stopped treatment. Responders who discontinued efalizumab could restart treatment if symptoms worsened. PGA response was evaluated at Weeks 12 (primary endpoint) and 20, as were the proportions of patients achieving an improvement from baseline of >/=50%, >/=75% and >/=90% in Psoriasis Area and Severity Index (PASI) (PASI 50, PASI 75 and PASI 90, respectively). RESULTS: A total of 1,255 patients were included in the intention-to-treat population. At Week 12, 68.0% of patients had a PGA rating of "good" or better. Of 688 patients who entered the continuous-treatment period, 79.5% had a PGA rating of "good" or better at Week 20. At Week 12, median improvement in PASI score was 68.4%. PASI 50/75/90 was achieved by 65.5%/35.9%/13.0% of patients at Week 12, and by 78.2%/52.9%/24.3% of responders at Week 20. Of the 127 responders at Week 12 who discontinued efalizumab, 11% experienced rebound and 56.7% relapsed within 8 weeks after stopping therapy. Efalizumab was well tolerated during the study. CONCLUSIONS: Efalizumab provided effective control of psoriasis in the majority of patients during the initial treatment period. The high response rates were maintained in initial responders when treatment was continued beyond 12 weeks.

3% diclofenac in 2.5% hyaluronic acid (Solaraze) does not induce photosensitivity or phototoxicity alone or in combination with sunscreens.

Topical treatment with 3% diclofenac in 2.5% hyaluronic acid (Solaraze) has been extensively documented for the treatment of actinic keratoses (AK). Since sun protection is a vital part of AK management, two Phase IV studies were carried out to investigate the phototoxicity and photosensitisation potential of 3% diclofenac in 2.5% hyaluronic acid in combination with sunscreens. Patches of 3% diclofenac in 2.5% hyaluronic acid and control were applied under occlusion to the backs of healthy volunteers aged 18-65. In the phototoxicity study (n = 32), a single application followed by administration of the sunscreens and exposition with ultraviolet (UV) were done, whereas in the photosensitisation study, application was repeated twice weekly for three weeks, then once after a two-week rest phase. The erythema reaction was recorded, together with other local skin reactions. In both analyses, areas treated with 3% diclofenac in 2.5% hyaluronic acid in combination with sunscreens had the lowest incidence of erythema reactions, indicating that it was well tolerated when used in conjunction with sunscreen products, and with exposure to UV irradiation. The results showed that no phototoxic or photosensitisation reactions occurred with 3% diclofenac in 2.5% hyaluronic acid, either alone or in combination with sunscreens.

What's new in hypochromy.

Hypochromy is a common dermatological disorder. However, its treatment still gives unsatisfactory results. Interesting clues into the understanding of the pathophysiology of hypochromy have been recently brought about thanks to the pigmentary side effects reported with the new tyrosine kinase inhibition treatments. New therapeutic approaches to hypochromy are further discussed.

Use of the 308-nm excimer laser for psoriasis and vitiligo.

The 308-nm excimer laser represents the latest advance in the concept of selective phototherapy. It emits a wavelength in the UV-B spectrum and thus shares the same indications as conventional phototherapy. Like other laser devices, the 308-nm excimer laser emits a monochromatic and coherent beam of light, can selectively treat a lesion while sparing surrounding healthy skin, and can deliver high fluencies. Clinicians have taken advantage of these properties to treat dermatologic disorders since 1997, with psoriasis and vitiligo attracting most attention. Initially, high fluencies (minimal erythemal dose, 8-16) were used, with excellent clinical results, to treat psoriasis vulgaris. The significance of side effects and the potential long-term carcinogenic risk associated with such fluencies have resulted in medium doses (about 3 minimal erythemal dose) being recommended, however. Interestingly, taking advantage of the selectivity of the laser, newer treatment protocols adapt the dose to the lesion and not to the minimal erythemal dose, as is the case for conventional phototherapies. Many prospective study series have also shown the efficacy and the good tolerance of the 308-nm excimer laser in the treatment of localized vitiligo. Induced rates of repigmentation seem to be higher than with narrowband UV-B. Moreover, the selectivity of the treatment prevents irradiation of healthy skin and limits unsightly tanning of surrounding skin. Aesthetically pleasing results are usually not achieved in extremities and bony prominences, which are not good indications for this technique. Combining the 308-nm excimer laser with 0.1% tacrolimus ointment has provided very interesting results, which need to be confirmed in larger series. The absence of actual data concerning the long-term risk for skin cancer after this treatment means that it should be considered with caution. Combination with topical steroids appears to be synergistic and potentially reduces long-term side effects; again, prospective data are lacking.

Melanin pigmentary disorders: treatment update.

Most of the melanin pigmentary disorders are cosmetically important and have a strong impact on the quality of life of affected individuals. This article examines recent advances in the treatment of melanin pigmentary disorder including hypermelanosis and hypomelanosis. The development of laser technologies has completed the use of the increasing number of bleaching agents in treating hyperpigmented lesions. The treatment of hypomelanotic disorders is still often disappointing, but new therapeutic options provide encouraging results.

[The 308 nm excimer laser in dermatology]. / Le laser excimer à 308 nm en dermatologie.

THE EFFICACY OF THE 308 NM EXCIMER LASER in the treatment of common psoriasis has been demonstrated. THE DOSES USED have progressively decreased, hence, limiting the adverse events that appear redhibitory with high doses. THE ADAPTATION OF THE DOSES not to the patients themselves but to each of the plaques treated should reduce the number of sessions and the cumulated close necessary to obtain clinical remission. THE 308 NM EXCIMER LASER is effective and tolerance is good in the treatment of vitiligo. It should be proposed for limited vitiligo and essentially of the "UV sensitive" areas, which have shown aesthetically correct percentage of repigmentation. THE PLACE AND INTEREST of its association with other treatments, notably with topical tacrolimus, remains to be defined. Although the results obtained in the treatment of vitiligo are promising, they have to be confirmed in larger cohorts and ensure the absence of median and long term side effects. This therefore limits its use in combined treatments in the context of controlled clinical traits. THE 30 NM EXCIMER LASER IS AN EFFECTIVE AND WELL TOLERATED TREATMENT in localised and non-nodular forms of mycosis fungoid (MF). Although the number of patients treated is limited, the clinical and histological cure observed demonstrates the interest of this new technique in the treatment of MF. These results must be confirmed in a greater number of patients. THE 308 NM EXCIMER LASER is an interesting therapeutic alternative in the treatment of plaques of alopecia areata, erosive oral lichen planus, post-surgical hypopigmentation, vergetures and localised forms of atopic dermatitis. Because of the sparcity of data and in the absence of long term follow-up, it must not be proposed in first intention.

Topical tacrolimus and the 308-nm excimer laser: a synergistic combination for the treatment of vitiligo.

OBJECTIVE: To compare the efficacy of combined tacrolimus and 308-nm excimer laser therapy vs 308-nm excimer laser monotherapy in treating vitiligo. DESIGN: Comparative, prospective, randomized, intraindividual study. PATIENTS: Fourteen patients, aged 12 to 63 years, with Fitzpatrick skin types II to IV. INTERVENTION: For each patient, 4 to 10 target lesions were chosen. The treatment applied to each target lesion was randomized by drawing lots. Each lesion was treated twice a week by the 308-nm excimer laser, for a total of 24 sessions. Initial fluences were 12 mcal/cm(2) (50 mJ/cm(2)) less than the minimal erythemal dose in vitiliginous skin. Then, fluences were increased by 12 mcal/cm(2) every second session. Moreover, topical 0.1% tacrolimus ointment was applied twice daily on target lesions receiving the combined tacrolimus and excimer laser treatment (group A). Group B target lesions received only excimer laser monotherapy. For each treated lesion, the untreated lesion on the opposite side served as the control. Tolerance was evaluated by a visual analog scale, and secondary events were recorded at each session. MAIN OUTCOME MEASURE: Treatment efficacy, which was blindly evaluated by 2 independent physicians by direct and polarized light photographs taken before and after treatment. RESULTS: Forty-three lesions were treated (23 in group A and 20 in group B). All patients completed the study. Repigmentation was observed in all group A lesions (100%) and in 17 (85%) of the 20 group B lesions. Repigmentation was not observed in the untreated lesions (control group). A repigmentation rate of 75% or more was obtained in 16 (70%) of the 23 group A lesions and in 4 (20%) of the 20 group B lesions. In UV-sensitive areas (the face, neck, trunk, and limbs, with the exception of bony prominences and extremities), 10 (77%) of 13 group A lesions had a repigmentation rate of 75% or more vs 4 (57%) of 7 group B lesions. In classically UV-resistant areas, 6 (60%) of 10 group A lesions had a repigmentation rate of 75% or more vs 0 of the 13 group B lesions. The mean number of sessions necessary for an improvement of repigmentation was 10 in group A and 12 in group B. Adverse effects have been limited, and tolerance was excellent. CONCLUSIONS: The combination treatment of 0.1% tacrolimus ointment plus the 308-nm excimer laser is superior to 308-nm excimer laser monotherapy for the treatment of UV-resistant vitiliginous lesions (P<.002). The efficacy and the good tolerance of the 308-nm excimer laser in monotherapy for treating localized vitiligo were also confirmed, but this treatment regimen should be proposed only for UV-sensitive areas.

Alefacept: a novel and selective biologic agent for the treatment of chronic plaque psoriasis.

Psoriasis is a chronic immune-mediated disease affecting the skin and sometimes the joints. Approximately 14 million people in Europe have psoriasis and the disease has a profound effect on the quality of life of patients worldwide. Currently available therapies for psoriasis have several shortcomings, including organ-based toxicity, generalized immunosuppression, short duration of response, and inconvenient regimens. Alefacept is a recombinant, fully human fusion protein that selectively targets the memory T cell population implicated in psoriasis pathogenesis. Alefacept is unique among psoriasis treatments because of its selective therapeutic action, ability to induce lengthy disease remissions even in the absence of continued therapy, positive effect on quality of life, and favorable safety profile. Two courses of alefacept confer greater efficacy and duration of clinical improvement versus that observed with a single course. This novel biologic agent is currently approved in the United States and under regulatory review in Europe for moderate to severe chronic plaque psoriasis.

Patient satisfaction with psoriasis therapies: an update and introduction to biologic therapy.

BACKGROUND: Psoriasis is a chronic, immune-mediated skin condition that often requires lifelong treatment. Many patients report dissatisfaction with traditional nonbiologic therapies because they are ineffective for their psoriasis, are associated with side effects, or impact negatively on quality of life. OBJECTIVES: The aim of this article is to review the effect on patient quality of life of traditional nonbiologic psoriasis therapies and to discuss the impact of biologic psoriasis therapies on patient satisfaction. METHODS: A review of the literature is presented. RESULTS: Traditional nonbiologic psoriasis therapies can negatively impact quality of life due to a variety of factors including inconvenience and toxicity. Biologic agents have been developed that target the immunopathogenesis of psoriasis. Based on favorable efficacy and safety results in clinical trials, some of these agents are now approved for clinical use. Evidence suggests that patients receiving biologic therapies experience significant improvements in health-related quality of life. CONCLUSION: Biologic agents offer new hope for patients with psoriasis that their chronic condition can be controlled in a manner that improves their quality of life and may lead to high levels of satisfaction with their treatment.