Nicholas J. Lowe

CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris

Engagement of the B7 family of molecules on antigen-presenting cells with their T cell-associated ligands, CD28 and CD152 (cytotoxic T lymphocyte-associated antigen-4 [CTLA-4]), provides a pivotal costimulatory signal in T-cell activation. We investigated the role of the CD28/CD152 pathway in psoriasis in a 26-week, phase I, open-label dose-escalation study. The importance of this pathway in the generation of humoral immune responses to T cell-dependent neoantigens, bacteriophage phiX174 and keyhole limpet hemocyanin, was also evaluated. Forty-three patients with stable psoriasis vulgaris received 4 infusions of the soluble chimeric protein CTLA4Ig (BMS-188667). Forty-six percent of all study patients achieved a 50% or greater sustained improvement in clinical disease activity, with progressively greater effects observed in the highest-dosing cohorts. Improvement in these patients was associated with quantitative reduction in epidermal hyperplasia, which correlated with quantitative reduction in skin-infiltrating T cells. No markedly increased rate of intralesional T-cell apoptosis was identified, suggesting that the decreased number of lesional T cells was probably likely attributable to an inhibition of T-cell proliferation, T-cell recruitment, and/or apoptosis of antigen-specific T cells at extralesional sites. Altered antibody responses to T cell-dependent neoantigens were observed, but immunologic tolerance to these antigens was not demonstrated. This study illustrates the importance of the CD28/CD152 pathway in the pathogenesis of psoriasis and suggests a potential therapeutic use for this novel immunomodulatory approach in an array of T cell-mediated diseases.

A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin

BACKGROUND Beta carotene has been associated with a decreased risk of human cancer in many studies employing dietary questionnaires or blood measurements, and it has had protective effects in some animal models of carcinogenesis. METHODS We tested the possible cancer-preventing effects of beta carotene by randomly assigning 1805 patients who had had a recent nonmelanoma skin cancer to receive either 50 mg of beta carotene or placebo per day and by conducting annual skin examinations to determine the occurrence of new nonmelanoma skin cancer. RESULTS Adherence to the prescribed treatment was good, and after one year the actively treated groups median plasma beta carotene level (3021 nmol per liter) was much higher than that of the control group (354 nmol per liter). After five years of follow-up, however, there was no difference between the groups in the rate of occurrence of the first new nonmelanoma skin cancer (relative rate, 1.05; 95 percent confidence interval, 0.91 to 1.22). In subgroup analyses, active treatment showed no efficacy either in the patients whose initial plasma beta carotene level was in the lowest quartile or in those who currently smoked. There was also no significant difference between treated and control groups in the mean number of new nonmelanoma skin cancers per patient-year. CONCLUSIONS In persons with a previous nonmelanoma skin cancer, treatment with beta carotene does not reduce the occurrence of new skin cancers over a five-year period of treatment and observation.

Adverse Reactions to Dermal Fillers: Review

BACKGROUND For many patients, injectable filling agents offer the promise of facial rejuvenation while offering reduced risks compared with more invasive surgery. With the increase in products available and the rise in the number of patients seeking this type of intervention, it is crucial that both the physician and the patient are fully cognizant of the risks involved with each product. OBJECTIVE To review the incidences and types of reaction to various commonly used injectable products. METHODS A literature review and personal experiences (gained largely in Europe over the past 8 years) of dermal fillers from 1996 to the present, including illustrative case reviews. RESULTS Reactions can be attributed to the procedure itself, the procedural technique, and the agent injected. Some of these reactions are preventable, whereas others are inevitable; most are mild and transient. Improving product formulations, altering the concentration of product injected, or changing the injection technique can dramatically reduce the incidence of adverse reactions. Since its reformulation in mid-1999, the biologically engineered hyaluronic acid filler Restylane (Medicis Pharmaceuticals, Scottsdale, AZ, USA) elicits less than one allergic reaction in 1600 treatments. Skin reactions with poly-L-lactic acid (New-Fill/Sculptra, Dermik Laboratories, Berwyn, PA, USA) are considerably less likely if a greater dilution and deeper injection technique are employed. CONCLUSION Different injectable products have highly divergent properties, associated risks, and injection requirements. The dermasurgeon should be suitably experienced to select and use these products correctly.

Skin resurfacing with the Ultrapulse carbon dioxide laser. Observations on 100 patients.

background The Ultrapulse carbon dioxide (CO2) laser has been shown to be a highly effective treatment for photodamaged skin including improvement of rhytides, precancerous and benign skin lesions, as well as superficial benign pigmented lesions. objective We describe our experiences using the Ultrapulse CO2 laser in treating 100 patients with different severities of photodamaged skin. methods All patients had moderately or severely photodamaged skin and were selected for treatment with the Ultrapulse CO2 laser to evaluate the efficacy and toxicity of this treatment. The patients were placed on a pretreatment regimen for 2–6 weeks prior to receiving treatment with the Ultrapulse CO2 laser. Patients were evaluated for pre‐ and posttreatment severity of photodamage. In addition, skin surface replicas were obtained in selected patients and evaluated by computer image analysis technology. results At 1 month post‐laser treatment, 68 patients received a moderate improvement, five patients achieved a marked improvement, and the remaining 27 patients showed minimal improvement. By 2 months post‐laser treatment, 20 of the 27 patients who at 1 month showed only minimal improvement revealed a moderate to marked improvement from baseline. All the patients studied developed a transient erythema that lasted up to 6 weeks, and many of these patients showed a transient hyperpigmentation that persisted for up to 4 months. conclusion The Ultrapulse CO2 laser is confirmed as an effective treatment for skin resurfacing of photodamaged skin.

PUVA therapy for psoriasis: comparison of oral and bath-water delivery of 8-methoxypsoralen.

A direct clinical comparison has been made of the efficacy of oral 8-methoxypsoralen with bath-water delivery of 8-methoxypsoralen during psoralen ultraviolet A (PUVA) phototherapy for a group of forty patients with stable plaque-type psoriasis vulgaris. The 8-methoxypsoralen concentration was 3.7 mg/liter in the bath water. The efficacy of these treatments was assessed by their ability to improve or clear the psoriasis. The skin of eight of the twenty patients with oral psoralen cleared, and another eight showed good improvement. Of the twenty patients who received 8-methoxypsoralen in bath water, eight patients had clearing of the skin, whereas nine patients had good improvement during the initial 8-week treatment period. Administration of 8-methoxypsoralen in bath water required much lower ultraviolet A irradiance to achieve maximum improvement. There were no systemic side effects in the patients treated by bath-water delivery; however, some patients did develop phototoxic erythema. Minimal phototoxic doses were also studied in patients and in volunteers using both routes of psoralen delivery. The minimal phototoxic dose threshold after psoralen bath delivery gradually declined over five treatments from 5.3 +/- 0.6 joules/cm2 to 2.8 +/- 0.3 joules/cm2, suggesting an accumulation of psoralen in the skin with this method of drug delivery. Bath-water delivery of 8-methoxypsoralen was therefore found to be as effective as oral administration of 8-methoxypsoralen and yet required smaller amounts of ultraviolet A radiation and yielded fewer side effects. It would thus seem to be confirmed as a useful alternative means of 8-methoxypsoralen administration in PUVA therapy.

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.

Laser Skin Resurfacing with the Silk Touch Flashscanner for Facial Rhytides

background Effective treatment of facial rhytides has been reported using carbon dioxide (CO2) lasers with high peak power and short exposure time which creates char‐free ablation. Char‐free ablation can also be created using a Silktouch Flashscanner attached to n conventional CO2 laser. objective The purpose of this study is to evaluate the effectiveness of the SilkTouch Flashscanner in skin resurfacing. methods The SilkTouch Flashscanner attached to one of two continuous wave CO2 lasers was used to treat facial rhytides on 40 patients. Histopathology to evaluate the depth of penetration of the scanner on both CO2 lasers was performed on preauricular skin prior to excision during facelift surgery. Silicone surface replicas were obtained pre‐ and 2 months post‐laser treatment on two patients and evaluated by optical micrometry. Clinical evaluation of all patients pre‐ and post‐laser treatment was performed. results Clinical evaluation showed significant improvement of facial rhytides. Optical micrometry revealed a decrease in rhytide volume, indicating rhytide improvement. conclusion The Silktouch flashscanner is effective for the treatment of facial rhytides.

Acitretin plus UVB therapy for psoriasis. Comparisons with placebo plus UVB and acitretin alone

UVB radiation is beneficial for the treatment of psoriasis vulgaris. Patients with recalcitrant disease, however, are slow to respond to UVB phototherapy with and without the use of coal tars or emollients. Etretinate and, more recently, acitretin have proved useful, but clinical improvement is slow when they are used as monotherapy in plaque psoriasis. Each drug also produces side effects, some of which are dose related. This study was designed to compare results of treatment with UVB combined with either acitretin (50 mg/day) or placebo to determine if psoriasis would respond faster and to less cumulative exposure to UVB and acitretin. The psoriatic disease cleared to a greater degree in patients treated with acitretin-UVB with fewer treatments and smaller amounts of UVB radiation than in patients treated with either placebo-UVB or acitretin alone.

Effect of botulinum toxin type A on quality of life measures in patients with excessive axillary sweating: a randomized controlled trial.

Summary Background  Botulinum toxin type A (BTX‐A) has been shown to be a safe and effective treatment for primary focal hyperhidrosis. However, the effect of BTX‐A therapy on quality of life (QOL) in patients with this condition has only recently begun to be studied in controlled clinical trials.

The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia

BACKGROUND Data suggest that androgenetic alopecia is a process dependent on dihydrotestosterone (DHT) and type 2 5alpha-reductase. Finasteride is a type 2 5alpha-reductase inhibitor that has been shown to slow further hair loss and improve hair growth in men with androgenetic alopecia. OBJECTIVE We attempted to determine the effect of finasteride on scalp skin and serum androgens. METHODS Men with androgenetic alopecia (N = 249) underwent scalp biopsies before and after receiving 0.01, 0.05, 0.2, 1, or 5 mg daily of finasteride or placebo for 42 days. RESULTS Scalp skin DHT levels declined significantly by 13.0% with placebo and by 14.9%, 61.6%, 56. 5%, 64.1%, and 69.4% with 0.01, 0.05, 0.2, 1, and 5 mg doses of finasteride, respectively. Serum DHT levels declined significantly (P <.001) by 49.5%, 68.6%, 71.4%, and 72.2% in the 0.05, 0.2, 1, and 5 mg finasteride treatment groups, respectively. CONCLUSION In this study, doses of finasteride as low as 0.2 mg per day maximally decreased both scalp skin and serum DHT levels. These data support the rationale used to conduct clinical trials in men with male pattern hair loss at doses of finasteride between 0.2 and 5 mg.