H. Irving Katz

A double-blind evaluation of topical capsaicin in pruritic psoriasis

BACKGROUNDnSubstance P, an undecapeptide neurotransmitter, has been implicated in the pathophysiology of psoriasis and pruritus.nnnOBJECTIVEnSafety and efficacy of topical capsaicin, a potent substance P depletor, were evaluated in patients with pruritic psoriasis.nnnMETHODSnPatients applied capsaicin 0.025% cream (n = 98) or vehicle (n = 99) four times a day for 6 weeks in this double-blind study. Efficacy was based on a physicians global evaluation and a combined psoriasis severity score including scaling, thickness, erythema, and pruritus.nnnRESULTSnCapsaicin-treated patients demonstrated significantly greater improvement in global evaluation (p = 0.024 after 4 weeks and p = 0.030 after 6 weeks) and in pruritus relief (p = 0.002 and p = 0.060, respectively), as well as a significantly greater reduction in combined psoriasis severity scores (p = 0.030 and p = 0.036, respectively). The most frequently reported side effect in both treatment groups was a transient burning sensation at application sites.nnnCONCLUSIONnTopically applied capsaicin effectively treats pruritic psoriasis, a finding that supports a role for substance P in this disorder.

Acitretin in psoriasis: An overview of adverse effects

Oral retinoids are among the drugs of choice for pustular and erythrodermic psoriasis. In addition, retinoids are effective in combination with other topical and systemic agents for the treatment of plaque-type psoriasis. Acitretin, the active retinoid metabolite, has replaced etretinate in retinoid therapy of psoriasis because of its more favorable pharmacokinetic profile, including a significantly shorter half-life. Retinoids, including acitretin, are potent teratogens, leading to strict requirements for pregnancy prevention during and after their use. Other retinoid side effects are generally preventable or manageable through proper patient selection, dose adjustments, and routine monitoring. Mucocutaneous side effects such as cheilitis and hair loss are the most common dose-dependent side effects, requiring dose reduction in some patients. Less common effects such as hepatotoxicity, serum lipid alterations, pancreatitis, and possible skeletal effects are also discussed.

Tretinoin emollient cream: a new therapy for photodamaged skin.

BACKGROUNDnTretinoin administered topically in 0.1% concentration has been shown to improve the wrinkling and irregular pigmentation of photoaged skin.nnnOBJECTIVEnThe 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.nnnMETHODSnThree 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.nnnRESULTSnTretinoin 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.nnnCONCLUSIONnTretinoin emollient cream 0.05% appears to be safe and effective in the treatment of photodamaged skin.

Drug interactions with itraconazole, fluconazole, and terbinafine and their management ☆ ☆☆ ★

A drug interaction develops when the effect of a drug is increased or decreased or when a new effect is produced by the prior, concurrent, or subsequent administration of the other. Before prescribing a drug, it is important to obtain a thorough drug history of the prescription and nonprescription medications taken by the patient. The nonprescription medications may include items such as nutritional supplements and herbal medications. The risk of side effects is an inevitable consequence of drug use. The frequency of adverse reactions is increased in those patients receiving multiple medications. Drug interactions reported in animal or in vitro studies may not necessarily develop in humans. When drug interactions are observed with a particular agent, it cannot be automatically assumed that all closely related drugs will necessarily produce the same interaction. However, caution is advised until sufficient experience accrues. The prescriber should not overestimate or underestimate the potential for a given drug interaction on the basis of personal experience alone. Drug interactions will not necessarily occur in every patient who is given a particular combination of drugs known to produce an interaction. For a clinically significant drug interaction to be manifest, several other factors may be relevant other than just using the two drugs. In many instances drug interactions can be predicted and therefore avoided if the pharmacodynamic effects, the pharmacokinetic properties, and the mechanisms of action of the 2 drugs in question are known. In the case of contraindicated drugs, it may be possible to use an alternative agent.

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

BACKGROUNDnThe ability of topical tretinoin to improve certain signs of skin photodamage has been shown previously.nnnOBJECTIVEnOur purpose was to assess the effectiveness of tretinoin emollient cream in maintaining or further improving photodamaged skin during extended use.nnnMETHODSnPhotodamaged 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.nnnRESULTSnMaintenance 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.nnnCONCLUSIONnBoth 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.

Effects of acitretin on the liver

BACKGROUNDnTherapy with aromatic retinoids for psoriasis is associated with abnormal liver function test findings and toxic hepatitis (in 1.5% of patients).nnnOBJECTIVEnOur purpose was to determine the safety of acitretin with respect to liver function, on the basis of biopsy.nnnMETHODSnWe treated 128 adults (with chronic, stable psoriasis) with oral acitretin (25-75 mg/day) for four 6-month intervals in a prospective, open-label, 2-year multicenter study. Liver biopsies were performed before and after study completion (2 years).nnnRESULTSnEighty-three available pairs of pretreatment and posttreatment liver biopsies demonstrated no change in 49 patients (59%), improvement in 20 (24%), and worsening in 14 (17%). Of these 14 patients with decrements in biopsy status, most changes were mild. There was no correlation between liver function test abnormalities or cumulative acitretin dose and changes in liver biopsy status.nnnCONCLUSIONnAcitretin therapy elicited no biopsy-proven hepatotoxicity in this prospective 2-year study. These findings suggest that periodic liver biopsy may not be necessary with acitretin treatment.

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

BACKGROUNDnFluconazole is a bis-triazole antifungal agent approved for the treatment of oropharyngeal, esophageal, and vaginal candidiasis, serious systemic candidal infections, and cryptococcal meningitis.nnnOBJECTIVEnThe 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.nnnMETHODSnIn 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.nnnRESULTSnAt 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.nnnCONCLUSIONnResults of this study support the efficacy and safety of fluconazole in the treatment of distal subungual onychomycosis of the toenail.

Efficacy and safety of twice-daily augmented betamethasone dipropionate lotion versus clobetasol propionate solution in patients with moderate-to-severe scalp psoriasis.

This 2-week, randomized, multicenter, investigator-blinded, parallel-group study was conducted to compare the efficacy and safety of augmented betamethasone dipropionate 0.05% lotion and clobetasol propionate 0.05% solution in the treatment of moderate-to-severe scalp psoriasis among 197 (193 assessable) healthy adult patients with at least 20% scalp-surface involvement. The patients received one of two treatments applied twice a day for 2 weeks. Signs and symptoms were evaluated at baseline, after 3 days (day 4), and after weeks 1 (day 8) and 2 (day 15) of treatment. As early as 3 days after treatment, scaling and induration were improved significantly faster by betamethasone dipropionate than by clobetasol propionate. Both treatments also reduced erythema and pruritus. Patients receiving betamethasone dipropionate had a significantly greater mean percent improvement in total sign/symptom scores (P < or = 0.015) at all visits and better mean global clinical response scores at the early visits (days 4 and 8) (P < or = 0.017). At the end of the study, only mild disease was present in both groups. Adverse events were reported by 34.0% and 36.4% of patients receiving betamethasone dipropionate and clobetasol propionate, respectively. All events were transient, most were mild and local, and no discontinuations resulted. The effects of treatment on the hypothalamic-pituitary-adrenal axis were not measured. In conclusion, augmented betamethasone dipropionate lotion and clobetasol propionate solution were equally effective, but betamethasone dipropionate lotion provided a faster onset of relief for scaling and induration, which may enhance patient compliance and patient satisfaction with treatment.

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

BACKGROUNDnPrevious studies have documented reversal of long-term photodamage with once-daily applications of topical tretinoin.nnnOBJECTIVEnOur purpose was to assess the effectiveness of tretinoin emollient cream in maintaining improvement in photodamage with a reduced frequency of applications.nnnMETHODSnA 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.nnnRESULTSnThe 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.nnnCONCLUSIONnAfter 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.

Preatrophy: Covert sign of thinned skin

Overt iatrogenic cutaneous atrophy is easily recognized; however, the earliest signs of such an adverse event may be covert. Preatrophy is proposed as a term to describe the subtle unmasking or normally covert subpapillary vascular channels found by the use of enhanced skin surface magnification techniques. We conducted a randomized double-blind, bilaterally paired comparison clinical trial in patients with chronic plaque psoriasis treated with twice-daily (nonoccluded) superpotent topical steroids for 2 weeks. Occult reversible delicate networks of horizontally oriented vascular channels were found within and surrounding 20% (23/118) of the involved psoriatic plaques during the course of the study. The use of a hand-held magnifying lens (8X), mineral oil, a coverglass, and adequate illumination allow recognition of preatrophy. Preatrophy was more frequently found in women than in men.