Imiquimod in combination with meglumine antimoniate for cutaneous leishmaniasis: a randomized assessor-blind controlled trial

OBJECTIVE: To determine the efficacy and safety of imiquimod in combination with meglumine antimoniate in treating cutaneous leishmaniasis. DESIGN: Prospective, randomized, assessor-blind, parallel-design, placebo-controlled trial. SETTING: Two primary care health clinics. PATIENTS: One hundred nineteen patients (59 patients in the imiquimod group and 60 in the placebo group) were included in the study. INTERVENTIONS: Patients were randomly assigned to receive a combined 4-week course of imiquimod or placebo with meglumine antimoniate treatment (20 mg/kg of pentavalent antimony daily for 2 weeks) in an endemic area of Leishmania tropica. MAIN OUTCOME MEASURES: The primary end point was clinical cure, defined as more than 75% reduction in the size of lesions compared with baseline at week 8. RESULTS: At the end of the 4-week treatment period, clinical cure was similar in both groups (11 patients [18.6%] in the imiquimod-treated group vs 18 patients [30.0%] in the placebo group) (P = .15). Four weeks after the end of treatment, 26 patients (44.1%) and 29 patients (48.3%) in the imiquimod-treated and placebo groups, respectively, were cured (P = .64). Pruritus and burning sensation were reported by 3 patients treated with imiquimod and by no patients treated with placebo. CONCLUSION: This study showed no beneficial effect of combining a 4-week course of treatment with 5% imiquimod cream and a standard course of treatment with meglumine antimoniate in patients with cutaneous leishmaniasis in an endemic area of L tropica. TRIAL REGISTRATION: isrctn.org Identifier:ISRCTN77659407 and Cochrane Skin Group Identifier: CSG Trial No. 32.     

Supplementation with oral probiotic bacteria protects human cutaneous immune homeostasis after UV exposure-double blind, randomized, placebo controlled clinical trial

There is now strong evidence that probiotic bacteria can regulate inflammatory immune responses. Here, we analyzed whether oral supplementation with the probiotic bacterial strain Lactobacillus johnsonii (La1) could interfere with skin immune status following UV exposure. A randomized, double-blind, placebo controlled clinical trial was conducted with 54 healthy volunteers receiving either La1 or placebo, during six weeks prior to solar-simulated UV irradiation. Blister roofs and skin biopsies were recovered 1, 4 and 10 days after UV exposure from un-irradiated and irradiated skin and used for immunohistochemical analysis and mixed epidermal cell lymphocyte reaction (MECLR), respectively. La1 supplementation did not prevent the UV-induced phenotypic maturation of Langerhans cells (LCs) or the decrease in MECLR in irradiated skin samples, one day post-irradiation. On day 4, MECLR was still decreased in the placebo group, with a parallel reduction in the CD1a LC marker in irradiated epidermis. In contrast, the allostimulatory capacity of epidermal cells was totally recovered in the La1 group correlating with the normalization of CD1a expression within the epidermis. For the first time, the results provide evidence that ingested probiotic bacteria accelerate the recovery of skin immune homeostasis after UV-induced immunosuppression.     

Efficacy of sunscreen with photolyase or regular sunscreen associated with topical antioxidants in treating advanced photodamage and cutaneous field cancerization: a randomized clinical trial

BackgroundSeveral treatments are available for skin with advanced photodamage, which is characterized by the presence of actinic keratoses (AK).ObjectivesEvaluate the efficacy of using sunscreen with photolyase compared to regular sunscreen, as well as to compare the combination of a topical formulation of antioxidants versus placebo in the treatment of advanced photodamage.MethodsThis was a randomized, double-blind, factorial clinical trial. Participants with AKs on their forearms were randomized to apply regular sunscreen (SC) or sunscreen with photolyase (SC+P) on both forearms during the day. One of the forearms in each group was randomized again to receive topical antioxidants (AOx), and the other forearm received a placebo cream (both for night application). The four groups were SC/AOx, SC/placebo, SC+P/AOx, and SC+P/placebo. The duration of treatment was 8 weeks. Primary outcomes were total AK clearance, decrease in Forearm Photoaging Scale (FPS), and AK severity scores. Secondary outcomes were reduction in AK count, partial clearance rate, and safety.ResultsForty participants (80 forearms) were included. All groups showed significant improvement in outcomes at week eight. There were no significant differences between SC and SC+P for either outcome. AOx led to a significant reduction in AK count (22%; p < 0.05). Partial clearance was obtained in 18 (47.4%) forearms treated with AOx and in 9 (23.7%) treated with placebo (p < 0.05). All groups reduced the FPS score, without significant differences among them.Study limitationsShort interval of follow-up and absence of re-evaluation in the absence of treatment were limitations of the present study.ConclusionsThere is no difference in the treatment of advanced photodamage skin when comparing the use of sunscreen with photolyase and regular sunscreen, and topical antioxidants were more efficient in reducing AK count than placebo.     

A randomized controlled proof-of-concept trial of digoxin and furosemide in adults with cutaneous warts

This is a study of the effect of two topically-applied (i.e. applied to the skin) drugs, digoxin and furosemide, on the healing of viral warts on the skin. It was performed by a group from the Netherlands and Pennsylvania, USA. The investigation is known as a proof of concept study, which is a preliminary experiment to show whether there is likely to be a benefit of a particular course of treatment. These two medicines are believed to improve healing rates of viral warts because they block the passage of potassium into cells, a process that is necessary for the growth of wart viruses in human skin. The team used a topically applied preparation containing the two medications and measured the size of warts, the presence of visible features on their surface and their disappearance; in addition, samples were taken for testing for the presence of wart virus. All the patients had warts that had not responded to other treatments. The study followed different groups of 20 patients who received either both medications combined, each singly or a placebo. This showed that after 6 weeks of daily treatment and a follow up of 14 weeks, only those patients who had received the treatment with both digoxin and furosemide together showed improvements, with some achieving elimination of the warts. This is an encouraging result, but the work should now be carried out on a larger number of patients with warts that have not been treated before as, although the new treatment led to greater improvement, the numbers of patients whose warts disappeared completely was small. There were no side effects associated with the treatment.     

Silver nitrate cautery in aphthous stomatitis: a randomized controlled trial

BACKGROUND: Aphthous stomatitis is a painful, recurrent disease of the oral mucous membrane. Silver nitrate sticks have been used for a long time to provide pain relief for the duration of an aphthous ulceration, with only one application. Silver nitrate causes chemical cauterization and increases the depth of injury. OBJECTIVES: To study the effect of chemical cautery with silver nitrate in reducing pain of aphthous ulceration and to determine if this treatment shortens or prolongs healing. METHODS: In a randomized, patient-blinded, placebo-controlled study, 97 patients with painful minor oral aphthous ulceration were randomized to receive silver nitrate cautery or placebo. The severity of pain was rated on a three-category scale (severe, mild, none) and was recorded each day until the seventh day after the procedure. The lesion size was recorded at the time of the procedure and on the seventh day afterwards. In the treatment group, the ulcer was gently painted with a silver nitrate stick until it turned white. In the placebo group, the ulcer was gently painted with a placebo stick. RESULTS: In the treatment group, 33 of 47 patients (70%) evaluated and in the placebo group, four of 38 patients (11%) evaluated had reduction in severity of pain 1 day after the procedure. The difference was statistically significant (P < 0.001). On the seventh day after the procedure, the ulcers were completely re-epithelialized in 39 patients (83%) in the treatment group and in 34 patients (89%) in the placebo group. The difference was not statistically significant (P = 0.39). CONCLUSIONS: The results of our study showed that one application of silver nitrate can decrease the severity of pain in aphthous ulceration without significantly shortening or prolonging healing time. We did not observe any side-effects in our study. The effect is rapid and lasts for the duration of the lesion. The treatment is simple and cost-effective in patients with infrequent recurrences.     

Galvano-puncture and dermabrasion for striae distensae: a randomized controlled trial

Objective: To assess the effects of galvano-puncture (GG) and dermabrasion (DG) in reducing striae distensae in the gluteal region of women. Methods: This randomized, controlled, single-blind clinical trial was conducted at the UNIFAL-MG. Participants were 48 female who had striae distensae alba in the gluteal region. They were randomly divided in GG; DG; and Control Group (CG). The length and width of the largest striae were measured (in millimeters) using a caliper. The same striae were assessed before and after treatment. Infrared thermography was performed in the gluteal region to assess local microcirculation. Results: Intragroup analysis showed a significant reduction in the dimension of the striae between baseline and treatment session 10 in the GG and DG groups. Between-group analysis revealed a reduction in the width and length of the striae for both the GG and DG groups, but there were no significant differences between the two groups. When compared to the CG and the DG group, the GG group had significant improvements, as shown by thermography. Conclusion: Both GG and DG are effective in reducing striae length and width. However, only the thermography results showed significant differences between GG and control, and between GG and DG.     

Interferon-gamma in the treatment of systemic sclerosis: a randomized controlled multicentre trial

We report the results of a randomized controlled multicentre study on interferon-gamma (IFN-γ) treatment of systemic sclerosis as determined by skin sclerosis, renal and other organ involvement, global assessment, subjective symptoms and quality of life. Forty-four patients were enrolled into the trial, 27 in the treatment group and 17 in the control group. All patients presented with type I or type II scleroderma. Twenty-nine patients (64%) finished the study. The mean duration of Raynaud's phenomenon and skin sclerosis was 15.3 and 10.8 years, respectively. The skin scores tended to improve in the treatment group (P > 0.05). Mouth aperture increased significantly from 38.5 to 47.7 mm in the treatment group (P < 0.001). Subanalysis of IFN-γ treated patients with normalized skin sclerosis scores ≥1 showed significant improvement in both skin involvement and subjective symptoms (P < 0.05). Organ involvement improved in eight of 18 treatment patients and in three of 11 control patients. It worsened in three of 18 treatment patients and in four of 11 control patients. One control patient died due to cardiorespiratory failure during the study. No deterioration of renal function occurred during IFN-γ treatment. There was a significant improvement in quality of life parameters in the control group but not in the treatment group. Plasma levels of neopterin increased significantly during IFN-γ treatment but not in the control group, whereas N-terminal procollagen III peptide levels did not change in either group. There was a high frequency of mild to moderate influenza-like adverse events during IFN-γ treatment. Only four of nine drop-out patients, however, experienced symptoms most probably associated with IFN-γ treatment. We conclude that IFN-γ therapy has mild beneficial effects on skin sclerosis and disease-associated symptoms in type I and II scleroderma. IFN-γ treatment was associated with acceptable tolerability and did not induce major renal dysfunction in our patients.     

Patient-delivered partner treatment for Trichomonas vaginalis infection: a randomized controlled trial

OBJECTIVES: Infections with Trichomonas vaginalis (TV) are common and recurrence rates are high. Better methods of treating partners of women with trichomoniasis are needed. GOAL: To determine if patient-delivered partner treatment (PDPT) is better and more cost-effective than partner referral. STUDY DESIGN: Women attending a family planning clinic who were culture-positive and treated for TV (N = 463) were randomized to either standard partner referral (PR), booklet-enhanced partner referral (BEPR), or PDPT. At baseline and 1 month, women were interviewed and cultured for TV. Detailed cost information was also collected. RESULTS: Most women had 1 partner, were less than 24 years old, and were black. The percentage of women reporting that their partners were treated was similar for PDPT but significantly lower for BEPR compared to PR. TV follow-up rates were similar. PDPT cost less and was cost saving compared to PR and BEPR. CONCLUSION: Among women with TV, PDPT did not result in more partners taking the medicine or lower follow-up rates than PR but was less costly.     

Efficacy of 0.1% tazarotene cream for the treatment of photodamage: a 12-month multicenter,randomized trial

OBJECTIVE: To determine the efficacy and safety of 0.1% tazarotene cream for the treatment of photodamage. DESIGN: A 24-week multicenter, double-blind, randomized, vehicle-controlled intervention study followed by a 28-week open-label extension. SETTING: Ambulatory patients in private and institutional practice. PATIENTS: Of 563 patients with facial photodamage, 91% and 86% completed the double-blind and open-label phases, respectively. In the double-blind phase, 20 of 283 tazarotene-treated patients and 1 of 280 vehicle-treated patients discontinued treatment owing to adverse events. INTERVENTION: Once-daily application of 0.1% tazarotene cream or nonmedicated vehicle cream to the face for 24 weeks. Then, all continuing patients received treatment with 0.1% tazarotene cream for another 28 weeks. MAIN OUTCOME MEASURES: Primarily, fine wrinkling and mottled hyperpigmentation. Also, lentigines, elastosis, pore size, irregular depigmentation, tactile roughness, coarse wrinkling, telangiectasia, actinic keratoses, overall integrated assessment of photodamage, global response to treatment, patients' overall assessment of photodamage, and plasma levels of tazarotenic acid. RESULTS: Compared with the vehicle, at week 24 tazarotene resulted in a significantly greater incidence of patients achieving treatment success (>or=50% global improvement) and at least a 1-grade improvement in fine wrinkling, mottled hyperpigmentation, lentigines, elastosis, pore size, irregular depigmentation, tactile roughness, coarse wrinkling, and the overall integrated assessment of photodamage (P<.01). Additional clinical improvement occurred with continued tazarotene treatment and had not plateaued by week 52. Plasma tazarotenic acid concentrations did not exceed 0.71 ng/mL. CONCLUSIONS: Once-daily applications of 0.1% tazarotene cream significantly reduced multiple signs of photodamage. Plasma levels of tazarotenic acid remained below those of endogenous retinoids.     

Topical cyclosporin in oral lichen planus: a controlled, randomized, prospective trial

The published studies of topical cyclosporin (CyA) therapy in chronic oral lichen planus (OLP) have shown conflicting results. We report an investigator-blinded study of 13 patients with OLP, who were randomly assigned to treatment with CyA (500 mg as a swish-and-spit medication for 5 min three times daily) or a corticosteroid oral paste (triamcinolone acetonide). The duration of treatment was 6 weeks. Thereafter, patients on corticosteroid therapy were treated with CyA. Only slight, transient clinical improvement was observed in both groups after 6 weeks of treatment, compared with baseline. No significant differences could be demonstrated between the two groups. CyA therapy following corticosteroid treatment did not produce any further clinical improvement. During follow-up of the disease for up to 1 year after treatment, neither the CyA nor the corticosteroid group exhibited long-term improvement in disease activity. Contradictory results from earlier reports are discussed.     

Efficacy of short-course oral prednisolone in polymorphic light eruption: a randomized controlled trial

BACKGROUND: Polymorphic light eruption (PLE) is the most common so-called idiopathic photosensitivity disorder and affects up to 15% of the population in the U.K.; brief courses of systemic steroids have been tried and anecdotally have apparently been dramatically effective in the treatment of acute attacks. OBJECTIVES: To assess the efficacy and safety of a short course of moderate-dose oral prednisolone used from the earliest onset of the eruption in the treatment of PLE. METHODS: The study was double-blind placebo-controlled, all patients being given both prednisolone and placebo, but randomized to take either one or the other from the earliest sign of onset of rash; if within 48 h there was no improvement, they transferred to the other medication. Each participant also applied a broad-spectrum, highly protective sunscreen 2-hourly during sun exposure, continued his or her usual degree of exposure after any development of PLE, and kept a diary noting details of the eruption, amount of exposure, weather conditions and any adverse events. Statistical analysis was performed by means of the non-parametric log rank test based on Kaplan-Meier plots and bootstrapped confidence intervals (CIs) for the means, using the time in days for the itch and rash to clear as the end-points. RESULTS: Twenty-one patients entered the study but only 10 required medication. Eight who took prednisolone first and remained on it or transferred to it from placebo all improved, with the itch settling fully within a mean 2.8 days of starting the prednisolone and the rash clearing by 4.2. In the two who took placebo first and remained on it, the itch took a mean 5.4 days to settle and the rash a mean 7.8. No patient who started with prednisolone changed to placebo. Thus, the prednisolone as randomized was better than placebo at settling both the itch (mean 2. 6 days less, CI 0.7-4.0, P = 0.015) and rash (mean 3.6 days less, CI 0.6-6.1, P = 0.036); only one patient experienced mild adverse effects of transient gastrointestinal upset and depressed mood. CONCLUSIONS: The acute eruption of PLE is likely to respond rapidly to short courses of prednisolone therapy given from the earliest onset of the condition, and the treatment is safe.