Michael Jarratt

A double-blind evaluation of topical capsaicin in pruritic psoriasis

BACKGROUND Substance P, an undecapeptide neurotransmitter, has been implicated in the pathophysiology of psoriasis and pruritus. OBJECTIVE Safety and efficacy of topical capsaicin, a potent substance P depletor, were evaluated in patients with pruritic psoriasis. METHODS Patients 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. RESULTS Capsaicin-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. CONCLUSION Topically applied capsaicin effectively treats pruritic psoriasis, a finding that supports a role for substance P in this disorder.

Topical methyl-aminolevulinate photodynamic therapy using red light-emitting diode light for treatment of multiple actinic keratoses: A randomized, double-blind, placebo-controlled study

BACKGROUND The use of light-emitting diode light offers practical advantages in photodynamic therapy (PDT) with topical methyl-aminolevulinate (MAL) for management of actinic keratoses (AK). OBJECTIVE We sought to evaluate the efficacy of MAL PDT using red light-emitting diode light. METHODS We conducted a multicenter, double-blind, randomized study. A total of 49 patients with 363 AK lesions had 16.8% MAL cream applied under occlusion for 3 hours, and 47 patients with 360 AK lesions had vehicle cream similarly applied. The lesions were then illuminated (630 nm, light dose 37 J/cm2) with repeated treatment 1 week later. Complete lesion and patient (all lesions showing complete response) response rates were evaluated 3 months after last treatment. RESULTS MAL PDT was superior (P<.0001) to vehicle PDT with respect to lesion complete response (86.2% vs 52.2%, odds ratio 6.9 [95% confidence interval 4.7-10.3]) and patient complete response (59.2% vs 14.9%, odds ratio 13.2 [95% confidence interval 4.1-43.1]). LIMITATIONS The study population may not be representative of all patients with AK. CONCLUSION MAL PDT using red light-emitting diode light is an appropriate treatment alternative for multiple AK lesions.

Photodynamic therapy with methyl aminolevulinate for primary nodular basal cell carcinoma: results of two randomized studies

Background  Data suggest that photodynamic therapy using topical methyl aminolevulinate (MAL PDT) may be a noninvasive alternative to excisional surgery for nodular basal cell carcinoma (BCC). In the studies described here, we investigated the histologic response, tolerability, and cosmetic outcome with MAL PDT for primary nodular BCC (≤ 5 mm in depth).

MAS063DP is effective monotherapy for mild to moderate atopic dermatitis in infants and children: a multicenter, randomized, vehicle-controlled study.

OBJECTIVE To examine the efficacy and safety of MAS063DP (Atopiclair) cream in the management of mild to moderate atopic dermatitis in infants and children. STUDY DESIGN One hundred forty-two patients aged 6 months to 12 years were administered MAS063DP (n = 72) or vehicle (n = 70) cream 3 times per day to affected areas and sites prone to develop atopic dermatitis. The primary endpoint for efficacy was the Investigators Global Assessment at day 22. Secondary endpoints included Investigators Global Assessment at other time-points, patients/caregivers assessment of pruritus, onset, duration of itch relief, Eczema Area and Severity Index, subjects/caregivers assessment of global response, and need for rescue medication in the event of an atopic dermatitis flare. RESULTS MAS063DP cream was statistically more effective (P < .0001) than vehicle cream for the primary endpoint and all secondary endpoints. Treatment discontinuation as a result of an adverse event occurred in 9.9% of patients using MAS063DP cream and 16% of patients using vehicle cream. CONCLUSION MAS063DP cream is effective and safe as monotherapy for the treatment of symptoms of mild to moderate atopic dermatitis in infants and children.

The efficacy and safety of a combination benzoyl peroxide/clindamycin topical gel compared with benzoyl peroxide alone and a benzoyl peroxide/erythromycin combination product.

A bstractBackground: Topical clindamycin and benzoyl peroxide have each demonstrated clinical efficacy in the treatment of acne vulgaris. When used in tandem, they promise greater efficacy than either individual agent through their antibacterial and anti-inflammatory effects. Objective: To determine the efficacy and safety of combination benzoyl peroxide/clindamycin compared with benzoyl peroxide or benzoyl peroxide/erythromycin in the treatment of acne. Methods: In this randomized, 10-week, multicenter, single-blind trial, 492 patients with moderate to moderately severe acne were treated twice daily with 5% benzoyl peroxide/1% clindamycin, 5% benzoyl peroxide, or 5% benzoyl peroxide/3% erythromycin and assessed every 2 weeks. Results: Compared with benzoyl peroxide, benzoyl peroxide/clindamycin demonstrated significantly greater reductions in inflammatory lesions (p = 0.04) and significantly greater overall improvement as assessed by physicians (p ? 0.04) and patients (p <0.001). Benzoyl peroxide/clindamycin demonstrated a nonsignificant trend for greater efficacy compared to benzoyl peroxide/erythromycin. Dry skin was the most frequent (?7.3%) adverse event with all three therapies. Conclusion: Benzoyl peroxide/clindamycin demonstrated improved efficacy and similar tolerability to benzoyl peroxide used alone and was similar to benzoyl peroxide/erythromycin, making this combination product an effective alternative antimicrobial therapy for acne.

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.

Hematologic Safety of Dapsone Gel, 5%, for Topical Treatment of Acne Vulgaris

OBJECTIVE To evaluate the risk of hemolysis in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency who were treated for acne vulgaris with either dapsone gel, 5% (dapsone gel), or vehicle gel. DESIGN Double-blind, randomized, vehicle-controlled, crossover study. SETTING Referral centers and private practice. PARTICIPANTS Sixty-four subjects 12 years or older with G6PD deficiency and acne vulgaris. Intervention Subjects were equally randomized to 1 of 2 sequences of 12-week treatment periods (vehicle followed by dapsone gel or dapsone gel followed by vehicle). The washout period was 2 weeks. Treatments were applied twice daily to the face and to other acne-affected areas of the neck, upper chest, upper back, and shoulders as required. MAIN OUTCOME MEASURES Results of clinical chemical analysis and hematology values; plasma dapsone and N-acetyl dapsone concentrations; spontaneous reports of adverse events. RESULTS A 0.32-g/dL decrease in hemoglobin concentration occurred from baseline to 2 weeks during dapsone gel treatment. This was not accompanied by changes in other laboratory parameters, including reticulocytes, haptoglobin, bilirubin, and lactate dehydrogenase levels, and was not apparent at 12 weeks as treatment continued. The number of subjects with a 1-g/dL drop in hemoglobin concentration was similar between treatment groups at both week 2 and week 12. The largest drops in hemoglobin concentration were 1.7 g/dL in the vehicle gel treatment group and 1.5 g/dL in the dapsone gel treatment group. No clinical signs or symptoms of hemolytic anemia were noted. CONCLUSIONS After treatment with dapsone gel, 5%, no clinical or laboratory evidence of drug-induced hemolytic anemia was noted in G6PD-deficient subjects with acne vulgaris. Trial Registration clinicaltrials.gov Identifier: NCT00243542.

Eosinophilic fasciitis: An early variant of scleroderma

Eosinophilic fasciitis, originally reported as a syndrome distinct from scleroderma, appears now to be an early inflammatory variant of scleroderma. No less than one half of the cases reported as eosinophilic fasciitis have convincing features of scleroderma, including Raynauds phenomenon, esophageal dysmotility, restrictive lung disease, diffuse hyperpigmentation, synovitis, flexion contractures, dermal sclerosis, colonic diverticula, scleroderma kidney, positive latex fixation test, and the presence of serum antinuclear antibodies (ANA). Clinical presentations of scleroderma range from isolated acrosclerosis to rapidly progressive systemic sclerosis. As clinical experience and long-term follow-up data on eosinophilic fasciitis accumulate, it appears that the syndrome may well represent another variant in the scleroderma spectrum. Reported here is a case which presented clinically and histologically as eosinophilic fasciitis, but which progressed over 3 years to diffuse, histologically confirmed scleroderma.

Patient‐reported outcomes from a multicenter, randomized, vehicle‐controlled clinical study of MAS063DP (Atopiclair™) in the management of mild‐to‐moderate atopic dermatitis in adults

Background: MAS063DP (Atopiclair™) is a topical cream approved for symptomatic relief in the treatment of atopic and contact dermatitis. Methods: This was a multicenter, randomized, double‐blind, vehicle‐controlled study in adults with mild–moderate atopic dermatitis. Patients were given MAS063DP or vehicle (2:1) three times per day to areas affected by atopic dermatitis for up to 50 days. A patient global assessment change from baseline was determined at days 8, 22, 36, and 50. Patient total body pruritus (visual analog scale) and patient opinion on treatment acceptability were also assessed. Results: A total of 218 patients (active: n = 145, vehicle: n = 73) were enrolled. At Day 22, 77% of patients on MAS063DP had a patient global assessment of good improvement or better versus 21% on vehicle (p<0.0001, chi‐squared test). Similarly, more patients had improvement in itch over their total body on MAS063DP than on vehicle (p<0.0001). Conclusion: MAS063DP treatment results in patient‐perceived improvements in mild–moderate atopic dermatitis.

Therapy of herpes simplex infection.

Recu rrent herpetic cutaneous infec tion is one of the most common and vexing problems seen by the practicing physician. Scores of topica l remed ies are recommended by phys icians and nonprofessionals alike. Each of the remed ies in the experience of some observers appears to be efficac ious. However, in sc ientifica lly designed, stati sticall y va lid, double-blind, con trolled studies of trea tments for cutaneous herpes simplex, not a si ngle topica l therapeutic modality has proven to be signifi ca ntly effec tive. Rec urrent herpes simplex in many patients becomes less frequent and severe over a period of weeks or months after the primary infection . Thus, any topica l remedy appli ed during the course of natural , spontaneous improvement may appea r to ameliorate the di sease. Unfortunately, no currently available therapeutic modality dec reases the rate at which recurrences occur. Several topica l agents, however, are purported to have therapeutic efficacy. Ether, a lipid so lvent that disrupts the envelope of herpes simplex virions and renders ex trace llular virus particles noninfec tious, was anecdotally reported to promote healing. 1 Recently, however, a well controlled double-blind clinical trial failed to show efficacy for topica l ether in the trea tment of cutaneous herpes simplex. 2 Moreover, ether MICHAEL JARRATT, M.D., RICHARD SMITH, M.D. AND JO HN M. KN O X, M.D.