Matthew J. Stiller

Tretinoin emollient cream: a new therapy for photodamaged skin.

BACKGROUND Tretinoin administered topically in 0.1% concentration has been shown to improve the wrinkling and irregular pigmentation of photoaged skin. OBJECTIVE The purpose of this study was to assess the safety and efficacy of various concentrations of tretinoin in a new emollient cream base in the treatment of photoaged skin. METHODS Three concentrations of tretinoin (0.05%, 0.01%, and 0.001%) in a new emollient cream formulation were compared with vehicle in a 24-week, double-blind, randomized, multicenter study of 296 subjects with photodamaged facial skin. RESULTS Tretinoin emollient cream 0.05% gave a significantly better global response to therapy than vehicle (p less than 0.001), with 68% of subjects exhibiting improvement at the end of therapy, compared with 43% of subjects in the vehicle group. An excellent or good response was found in 26% of subjects treated with tretinoin emollient cream 0.05% versus 11% of vehicle-treated subjects. Fine wrinkling, mottled hyperpigmentation, and roughness were more improved in subjects who received tretinoin emollient cream 0.05% than in vehicle-treated subjects (p less than 0.05). No significant difference was found between vehicle and tretinoin emollient cream 0.01% or 0.001%. Histologic examination showed increases in epidermal and granular layer thickness, decreased melanin content and compaction of the stratum corneum after therapy with tretinoin emollient cream 0.05% or 0.01%. Mild to moderate skin reactions, such as erythema, peeling, and burning, were the most common side effects and, although most prevalent in the group using the 0.05% concentration, generally did not limit tretinoin use. CONCLUSION Tretinoin emollient cream 0.05% appears to be safe and effective in the treatment of photodamaged skin.

A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial.

Summary A prospective, randomized, double‐bind, placebo‐controlled multicentre study assessed the clinical efficacy and safety of pulsed electromagnetic limb ulcer therapy (PELUT) in the healing of recalcitrant, predominantly venous leg ulcers. The portable device was used at home for 3 h daily during this 8‐week clinical trial as an adjunct to a wound dressing. Wound surface area, ulcer depth and pain intensity were assessed at weeks 0, 4 and 8. At week 8 the active group had a 47.7% decrease in wound surface area vs. a 42.3% increase for placebo (P<0.0002). Investigators global evaluations indicated that 50% of the ulcers in the active group healed or markedly improved vs. 0% in the placebo group, and 0% of the active group worsened vs. 54% of the placebo group (P<0.001). Significant decreases in wound depth (P<0.04) and pain intensity (P<0.04) favouring the active group were seen. Patients whose ulcers improved significantly after 8 weeks were permitted to continue double‐blind therapy for an additional 4 weeks. Elevan active and one placebo patient continued therapy until week 12, with the active treatment group continuing to show improvement. There were no reports of adverse events attributable to this device. We conclude that the PELUT device is a safe and effective adjunct to non‐surgical therapy for recalcitrant venous leg ulcers.

Fluorescence photography in the evaluation of acne

BACKGROUND Quantification of acne remains a challenge. It may be difficult to identify lesions by standard flash photography. Previous studies have shown that foci of light in fluorescence photographs correspond to high protoporphyrin IX production by Propionibacterium acnes in open comedones, follicles, and inflammatory lesions. OBJECTIVE Our purpose was to study the utility of fluorescence photography for evaluation of acne. METHODS Forty subjects with mild to moderate acne vulgaris were randomly selected to apply either clindamycin 1% topical solution or vehicle twice daily. Counts of acne lesions and flash and fluorescence photographs were obtained at baseline, and at 4, 8, and 12 weeks. RESULTS At 12 weeks, the treatment group had a larger percentage change in open comedones, less fluorescence in all areas assessed, and a larger percent decrease in fluorescence than the vehicle group. CONCLUSION Fluorescence photography appears to be a useful tool to chart the course of acne treatment.

Physical enhancement of dermatologic drug delivery: Iontophoresis and phonophoresis

Iontophoresis and phonophoresis are emerging technologies capable of enhancing drug penetration through the stratum corneum, the principal barrier to percutaneous absorption. With utilization of applied electric current or ultrasonic waves, respectively, iontophoresis and phonophoresis have shown efficacy in an increasing number of clinical applications. This article reviews the underlying principles, current status, and potential of iontophoresis and phonophoresis in dermatologic therapy.

Cyclosporine as maintenance therapy in patients with severe psoriasis

BACKGROUND Low-dose cyclosporine therapy for severe plaque psoriasis is effective. Most side effects can be controlled by patient monitoring, with appropriate dose adjustment or pharmacologic intervention, or both, if indicated. Prevention or reversibility of laboratory and chemical abnormalities may be achieved by discontinuation of therapy after the induction of clearing. However, relapse occurs rapidly on discontinuation. Maintenance therapy with cyclosporine after induction has not been fully evaluated. OBJECTIVE Our purpose was to compare a regimen of 3.0 mg/kg per day of oral cyclosporine with placebo in maintaining remission or improvement in patients with psoriasis. METHODS After a 16-week unblinded induction phase in which 181 patients received cyclosporine, 5.0 mg/kg per day (an increase up to 6.0 mg/kg per day and a decrease to 3.0 mg/kg per day were allowed, if required, to achieve efficacy or tolerability, respectively), those patients showing a 70% decrease or more in involved body surface area (BSA) entered the 24-week maintenance phase and were randomly assigned to either placebo, cyclosporine, 1.5 mg/kg per day, or cyclosporine, 3.0 mg/kg per day. Patients were considered to have had a relapse when BSA returned to 50% or more of the prestudy baseline value. Clinical efficacy, adverse effects, and laboratory values were monitored regularly throughout both study phases. RESULTS During induction, cyclosporine at approximately 5.0 mg/kg per day produced a reduction in BSA of 70% or more in 86% of the patients. During maintenance, the median time to relapse was 6 weeks in both the placebo and cyclosporine 1.5 mg/kg per day groups, but was longer than the 24-week maintenance period in the 3.0 mg/kg per day group (p < 0.001 vs placebo). By the end of the maintenance period, 42% of the patients in the 3.0 mg/kg per day cyclosporine group had a relapse compared with 84% in the placebo group. Changes in laboratory values associated with the higher induction dosage generally exhibited partial or complete return toward mean prestudy baseline values during the maintenance phase, with the greatest degree of normalization in the placebo group. CONCLUSION Cyclosporine, 3.0 mg/kg per day, adequately and safely maintained 58% of patients with psoriasis for a 6-month period after clearing of their psoriasis with doses of approximately 5.0 mg/kg per day.

Primary cutaneous infection by Aspergillus ustus in a 62-year-old liver transplant recipient

We report the first case of primary cutaneous aspergillosis caused by Aspergillus ustus, a species that seldom infects human beings. The patient, a 62-year-old liver transplant recipient with end-stage hepatitis C-induced cirrhosis, was receiving the experimental immunosuppressive drug FK-506. Trauma to the skin of the right arm from tape and from an arm board holding intravenous and intraarterial catheters in place and to the left leg from an occlusive knee brace may have contributed to this unusual mycosis. The patients cutaneous aspergillosis responded to a combination of intravenous amphotericin B and topical terbinafine cream. Although the patient died shortly thereafter from hepatic failure, there was no evidence of systemic aspergillosis.

Polarized light photography in the evaluation of photoaging

BACKGROUND The clinical characteristics of photodamaged skin, such as coarse and fine wrinkling, sallowness, hyperpigmentation, tactile roughness, laxity, and erythema, are not accurately evaluable from photographic records. OBJECTIVE The purpose of this study was to develop accurate and reproducible photographic techniques that generate an evaluable record of the characteristics of photodamaged skin. METHODS The method used involved illumination and photography through polarizing filters (polarized light photography). RESULTS Polarized light photography generates images that selectively enhance either the surface features or the subsurface features of the skin, providing an accurate and evaluable record for evaluation of photodamaged skin. CONCLUSION Polarized light photography, when coupled with precise framing and mapping, yields an accurate and evaluable record of photodamaged skin.

Efficacy of a 1-week, twice-daily regimen of terbinafine 1 % cream in the treatment of interdigital tinea pedis: Results of placebo-controlled, double-blind, multicenter trials

BACKGROUND Patients with tinea pedis often discontinue treatment before eradication of the fungus when their symptoms improve. The result is an incomplete cure/recurrence. OBJECTIVE Terbinafine, a topical fungicidal agent, was evaluated in double-blind, placebo-controlled trials (159 patients) for its ability to achieve cure and relief of symptoms in the same time frame, that is, before compliance wanes. METHODS Mycologic characteristics (with potassium hydroxide examination and culture) and clinical signs and symptoms were assessed at baseline, at the end of a 1-week, twice-daily treatment and at 1, 3, and 5 weeks after the completion of therapy. RESULTS Both terbinafine and vehicle provided early relief of symptoms. However, only terbinafine gave progressive mycologic improvement such that at 5 weeks after treatment, 88% of the patients receiving terbinafine had converted from positive to negative mycology compared with 23% of the patients treated with vehicle. CONCLUSION The rapid and potent fungicidal action of terbinafine results in a high cure rate in interdigital tinea pedis with 1 week of treatment and may avoid failures caused by non-compliance.

Haptoglobin is a natural regulator of Langerhans cell function in the skin

Langerhans cells (LC), the best-understood antigen presenting cells (APC) of the skin, are functionally plastic. Freshly obtained LC readily activate allogeneic T cells, but are incapable of activating autologous, naive T cells. When placed in culture in the presence of GM-CSF, LC up-regulate surface expression of class I and II MHC molecules along with co-stimulatory molecules, such as B7, CD40 and IL-12. This functional transformation enables the cells to activate naive, autologous T cells in vitro. It is paradoxical that intracutaneous administration of exogenous GM-CSF fails to induce intraepidermal LC to undergo functional transformation in situ. It has been reported that serum contains a factor that prevents fresh LC from undergoing functional transformation in culture, and the relevant serum factor has now been identified as haptoglobin (Hp), based on the following experimental results: (a) SDS-PAGE, amino acid sequencing, and mass spectrometric analyses of the inhibitory factor purified by high performance liquid chromatography (HPLC) from normal human serum revealed molecules completely homologous to Hp alpha-1 chain; (b) pure human Hp, but not serum depleted of Hp, inhibited fresh LC from acquiring the capacity to activate autologous T cells in vitro; (c) abundant Hp was detected in cytoplasmic compartments of fresh, but not cultured, LC. It was concluded that Hp, an acute phase protein, is a systemically-derived factor that prevents epidermal LC from spontaneously undergoing functional maturation in the skin. This novel property of Hp may be important in ameliorating or preventing certain T cell-dependent inflammatory skin diseases.

Elevation of fasting serum lipids in patients treated with low-dose cyclosporine for severe plaque-type psoriasis: An assessment of clinical significance when viewed as a risk factor for cardiovascular disease

BACKGROUND Hyperlipidemia has received little attention as a side effect of cyclosporine therapy for severe psoriasis. OBJECTIVE We report changes in fasting serum lipids in patients treated with low-dose oral cyclosporine for psoriasis and discuss their significance. METHODS Twenty-two patients with severe, recalcitrant, plaque-type psoriasis were treated with cyclosporine, 5 mg/kg/day, for 12 to 16 weeks. Fasting serum lipid levels (triglycerides, cholesterol, and high-density lipoproteins) were measured at 2-week intervals. RESULTS The mean serum triglyceride level increased from 117.8 +/- 11.7 mg/dl before initiation of therapy to 183.9 +/- 31.4 mg/dl after 2 weeks of treatment, without further significant change during the remainder of the study (p less than 0.007). A significant elevation of serum cholesterol from 207.1 +/- 8.1 mg/dl initially to 247.4 +/- 10.2 mg/dl after 2 weeks of treatment occurred (p less than 0.001) and persisted with continued cyclosporine therapy. No consistent alteration in high-density lipoprotein was noted (p less than 0.42). CONCLUSION Serum lipids should be closely monitored in psoriasis patients receiving intermediate or long-term therapy with cyclosporine, especially in the presence of elevated baseline values.