An investigator-initiated, double-blind, vehicle-controlled pilot study: assessment for tachyphylaxis to topically occluded halobetasol 0.05% ointment in the treatment of psoriasis.

BACKGROUND: Topical corticosteroids are the most common first-line treatment for psoriasis. Tachyphylaxis, a decreased response to treatment with repetitive application of the drug, is a controversial phenomenon associated with topical corticosteroid treatment. OBJECTIVE: We sought to prove or disprove tachyphylaxis to occluded halobetasol 0.05% versus vehicle. METHODS: Patients with plaque psoriasis were recruited to this study. The study involved 3 phases (1, 2A, and 2B) with each phase being separated by a treatment vacation period. In phases 1 and 2A, 2 plaques were randomized to either halobetasol 0.05% or vehicle ointment application. In phase 2B, halobetasol 0.05% was applied to both. Target Lesion Severity Scale was used for clinical assessment. RESULTS: Twenty patients were enrolled. No difference in time to clearance (P=.88) or time to recurrence (P=.92) of the treated plaques was found between phases 1 and 2A. Percentage of improvement was higher in phase 2A compared with phase 1 (89.4%, P<.05 vs 71%, P<.05), as a result of reduction of vehicle effect. In phase 2B, a greater improvement was found for previously corticosteroid-treated plaques. LIMITATIONS: Limitations are small sample size and 1 corticosteroid tested. CONCLUSION: No evidence of tachyphylaxis to the topical corticosteroid halobetasol 0.05% ointment treatment in patients with plaque psoriasis was found.

A single-blinded randomized controlled study to assess the efficacy of twice daily application of sinecatechins 15% ointment when used sequentially with cryotherapy in the treatment of external genital warts.

OBJECTIVE: To evaluate the efficacy of sequential therapy of cryotherapy and sinecatechins 15% ointment BID versus cryotherapy alone in treatment of external genital warts (EGW). METHODS: Forty-two subjects with at least two EGW lesions underwent cryotherapy to all lesions. One week following cryotherapy, subjects were randomized 1:1 to receive either no additional treatment or treatment with sinecatechins 15% ointment BID up to 16 weeks or until complete clearance. The total number of visible baseline and new EGW were recorded at each visit. Subjects were followed for a total of 65 weeks post-treatment. RESULTS: There was a significant reduction in mean number of lesions from baseline after 16 weeks of treatment in the cryotherapy-sinecatechins ointment group compared to cryotherapy alone (-5.0 lesions vs -2.1 lesions respectively, P=0.07). CONCLUSION: Cryotherapy plus sinecatechins 15% ointment BID resulted in a significant improvement in the reduction of EGW compared to cryotherapy alone. Clinicaltrials.gov registration identifier: NCT02147353.

Efficacy and safety of tretinoin 0.025%/clindamycin phosphate 1.2% gel in combination with benzoyl peroxide 6% cleansing cloths for the treatment of facial acne vulgaris.

Combination therapy using medications with complementary mechanisms of action is the standard of care in treating acne. We report results of a clinical trial evaluating the use of a fixed-dose tretinoin 0.025%/clindamycin phosphate 1.2% (T/CP) gel in combination with a benzoyl peroxide 6% foaming cloth compared with T/CP alone for facial acne. At week 12, the combination therapy group showed a trend toward greater efficacy compared with T/CP alone. There was a high success rate observed in the study, which may be attributable to the large percentage of adult female acne patients enrolled. Cutaneous adverse events were not statistically different in using combination therapy compared with T/CP alone.

Protein-losing enteropathy and joint contractures caused by a novel homozygous ANTXR2 mutation.

Infantile systemic hyalinosis (ISH) is a rare autosomal recessive disorder and an allelic form of hyaline fibromatosis syndrome that is caused by mutations in the ANTRX2 gene encoding the transmembrane anthrax toxin receptor 2. Its main features include characteristic skin lesions, joint contractures, persistent diarrhea, and failure to thrive due to accumulation of hyaline material in multiple organs. The resulting severe malnutrition can cause death in early infancy. Because of its rarity and high fatality rate, timely diagnosis is difficult and ISH may be underdiagnosed. In this report, we describe a 10-month-old male with severe protein-losing enteropathy, skin lesions, and painful joint contractures, diagnosed with ISH based on skin his-topathology and identification of a novel homozygous ANTRX2 mutation, c.1127_1128delTG (p.V376Gfs*14). While its clinical outcome is poor without curative treatment, establishing a diagnosis of ISH starting from clinical suspicion to molecular analysis is important for appropriate medical management and for risk and carrier assessment of family members.

Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial.

IMPORTANCE: Narrowband UV-B (NB-UV-B) phototherapy is used extensively to treat vitiligo. Afamelanotide, an analogue of α-melanocyte-stimulating hormone, is known to induce tanning of the skin. OBJECTIVE: To evaluate the efficacy and safety of combination therapy for generalized vitiligo consisting of afamelanotide implant and NB-UV-B phototherapy. DESIGN, SETTING, AND PARTICIPANTS: This study was performed in 2 academic outpatient dermatology centers and 1 private dermatology practice. We enrolled men and women 18 years or older with Fitzpatrick skin phototypes (SPTs) III to VI and a confirmed diagnosis of nonsegmental vitiligo that involved 15% to 50% of total body surface area. Vitiligo was stable or slowly progressive for 3 months. Patients were randomized to combination therapy (n = 28) vs NB-UV-B monotherapy (n = 27). After 1 month of NB-UV-B phototherapy, 16 mg of afamelanotide was administered subcutaneously to the combination therapy group monthly for 4 months while NB-UV-B phototherapy continued; the other group continued to receive NB-UV-B monotherapy. INTERVENTIONS: Narrowband UV-B monotherapy vs combined NB-UV-B phototherapy and afamelanotide. MAIN OUTCOMES AND MEASURES: Response on the Vitiligo Area Scoring Index and Vitiligo European Task Force scoring system. RESULTS: Response in the combination therapy group was superior to that in the NB-UV-B monotherapy group (P < .05) at day 56. For the face and upper extremities, a significantly higher percentage of patients in the combination therapy group achieved repigmentation, and at earlier times (face, 41.0 vs 61.0 days [P = .001]; upper extremities, 46.0 vs 69.0 days [P = .003]). In the combination therapy group, repigmentation was 48.64% (95% CI, 39.49%-57.80%) at day 168 vs 33.26% (95% CI, 24.18%-42.33%) in the NB-UV-B monotherapy group. Notable adverse events included erythema in both groups and minor infections and nausea in the combination therapy group. Comparison between Fitzpatrick SPTs showed patients with SPTs IV to VI in the combination therapy group had improvement in the Vitiligo Area Scoring Index at days 56 and 84 (P < .05); no significant difference was noted in patients with SPT III. CONCLUSIONS AND RELEVANCE: A combination of afamelanotide implant and NB-UV-B phototherapy resulted in clinically apparent, statistically significant superior and faster repigmentation compared with NB-UV-B monotherapy. The response was more noticeable in patients with SPTs IV to VI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01430195.

Retapamulin 1% Ointment and Clobetasol Propionate 0.05% Foam is More Efficacious than Vehicle Ointment and Clobetasol 0.05% Propionate Foam in the Treatment of Hand/Foot Dermatitis: A Single Center, Randomized, Double-blind Study.

BACKGROUND: Staphylococcus aureus has been implicated in the pathogenesis of adult hand/foot dermatitis. OBJECTIVE: The authors hypothesized that retapamulin 1% ointment and clobetasol propionate 0.05% foam would decrease disease severity in subjects with hand/foot dermatitis and provide a higher clearance of Staphylococcus aureus colonization, when compared to vehicle (placebo) ointment and clobetasol propionate 0.05% foam. METHODS: Adult subjects with moderate to very severe hand/foot dermatitis had twice-daily topical application of clobetasol propionate 0.05% foam to hands/feet for 14 days and were randomized to apply either retapamulin 1% ointment or vehicle ointment twice daily to hands/feet and nares for five days. RESULTS: Seventy-three percent of subjects in the retapamulin/clobetasol group were clear/almost clear at Day 15 compared to 47 percent of subjects in the vehicle/clobetasol group (p-value of 0.04). The percentage of subjects who had both negative skin and nares cultures and were clear/almost clear was also statistically significant in favor of the retapamulin/clobetasol group at Day 15 (p-value of 0.05). LIMITATIONS: Sample size, study population. CONCLUSION: At Day 15, retapamulin 1% ointment with clobetasol propionate 0.05% foam was more efficacious than vehicle ointment and clobetasol propionate 0.05% foam for disease improvement and Staphylococcus aureus clearance in adult subjects with hand/foot dermatitis.

Evaluating the Efficacy of Photodynamic Therapy with 20% Aminolevulinic Acid and Microdermabrasion as a Combination Treatment Regimen for Acne Scarring: A Split-face, Randomized, Double-blind Pilot Study.

Acne scarring is a consequence of abnormal resolution of wound healing after damage that occurs in the sebaceous follicle during acne inflammation. No trial to date has evaluated the efficacy of the combination of microdermabrasion and photodynamic therapy for acne scarring. This single-center, double-blinded pilot study enrolled subjects with moderate-to-severe acne scarring who were randomly assigned in a blinded fashion to use aminolevulinic acid and vehicle in a split-face fashion after full-face treatment with microdermabrasion. On average, 80 percent of the patients displayed more improvement in scarring on the aminolevulinic acid split face versus the vehicle split face after five treatments. Using two different noninvasive mechanisms of targeting acne scarring provided for a safe treatment regimen characterized by more efficacious results with respect to higher rates of scarring improvement.

An Investigator-initiated Study to Assess the Safety and Efficacy of Imiquimod 3.75% Cream When Used After Cryotherapy in the Treatment of Hypertrophic Actinic Keratoses on Dorsal Hands and Forearms.

OBJECTIVE: To evaluate the efficacy of combination cryotherapy and imiquimod 3.75% cream versus cryotherapy alone in the treatment of hypertrophic actinic keratosis on the dorsal hand and forearm. METHODS: Twenty subjects with at least three hypertrophic actinic keratoses on each dorsal hand or forearm underwent cryotherapy treatment to hypertrophic actinic keratoses. Following cryotherapy, subjects were randomized to have either their right or left dorsal hand or forearm treated with imiquimod 3.75% cream to begin on the same day as cryotherapy treatment. Subjects then utilized the two weeks on, two weeks off, two weeks on regimen of imiquimod 3.75% cream application. Local skin reactions were also assessed. RESULTS: For the cryotherapy/imiquimod 3.75% arm, the median total hypertrophic actinic keratosis reduction was -5.12 and for the cryotherapy alone arm, the median total hypertrophic actinic keratosis reduction was -2.24 (P<0.0094). LIMITATIONS: Local skin reactions unbind the investigator. CONCLUSION: Cryotherapy plus imiquimod 3.75% cream resulted in a statistically significant improvement in the reduction of hypertrophic actinic keratoses than cryotherapy alone at 14 weeks.

Infrared camera evaluation of the cooling effect of triamcinolone acetonide aerosol.

OBJECTIVE: Triamcinolone acetonide spray is a topical corticosteroid indicated for the relief of inflammatory/pruritic manifestations of corticosteroid-responsive dermatoses. There are clinical reports of an antipruritic, cooling sensation appreciated upon application. This study was designed to quantify the cryotherapeutic cooling effect of triamcinolone acetonide spray. DESIGN: Using an infrared video camera, skin surface temperature was evaluated for change upon application of the triamcinolone acetonide and two comparator ingredient components of triamcinolone acetonide: ethanol alcohol in a non-aerosolized spray and triamcinolone acetonide cream. SETTING: This was an open-label, single center, comparator study. PARTICIPANTS: This study enrolled 20 subjects with a diagnosis of either an acute or chronic steroid-responsive dermatosis. Ten additional controls were also enrolled. MEASUREMENTS: Using an infrared video camera, skin surface temperature was evaluated for change upon application of the triamcinolone acetonide and two comparator ingredient components of triamcinolone acetonide:ethanol alcohol in a non-aerosolized spray and triamcinolone acetonide cream. RESULTS: Across every study cohort, the average change in skin surface temperature with triamcinolone acetonide (between 16-18°C; P<0.001 for all comparisons, Figures 1 and 2) was significantly greater than the change demonstrated by both the non-aerosolized spray (between 5-7°C) and the triamcinolone acetonide cream (between 5.0-6.5°C). CONCLUSION: The transient temperature change of nearly 20°C with triamcinolone acetonide is most likely attributable to the refrigerant properties of the isobutane propellant of this product. Similar to other common cryotherapy methods, triamcinolone acetonide can achieve very low skin surface temperatures, which may result in localized relief of pruritus.