Journal of the European Academy of Dermatology and Venereology

Published by Wiley
Online ISSN: 1468-3083
Print ISSN: 0926-9959
Five per cent 5-fluorouracil (5-FU) cream is a well-established treatment for actinic keratosis (AK), and ingenol mebutate gel (IMB) is a novel topical field-directed therapy. To compare the tolerability and safety of IMB with that of 5-FU for the treatment of facial AK. An open-label, prospective, randomized, controlled clinical trial with 100 patients with AKs within a 25-cm(2) contiguous field on the face was conducted. IMB was applied daily for three consecutive days. 5-FU was applied twice a day for 4 weeks. The treatment effect and the adverse events were evaluated at baseline and on days 2, 3, 4, 8, 15, 22, 29, 36 and 43 for intent-to-treat populations. The mean (±SD) maximum local skin reactions (LSR) for patients treated with IMB was 10.85 (± 3.12), compared with 10.86 (± 3.55) for those who received 5-FU. Patients in the IMB group presented LSR that peaked at day 4 and almost completely regressed after 15 days. Differently, in the 5-FU group, the LSR peaked at day 29 and lasted until visit 36. Additionally, the area under the curve (LSR × visit) was significantly smaller for IMB. No differences between the treatments for pruritus, pain, tearing, conjunctival hyperaemia or headaches were noted, but the eyelid oedema rate was higher for IMB group. No significant difference in the proportion of dropouts was observed between groups. Both treatments demonstrated a suitable safety profile. For treating AKs, the local skin reactions in the IMB group were more short-lived compared with those of 5-FU, but both treatments seemed to be safe and tolerable. © 2015 European Academy of Dermatology and Venereology.
To compare the efficacy, safety and tolerability of adapalene gel 0.1% vs. tretinoingel 0.025% in a Chinese patient population. Although acne vulgaris is a common problem among Asians and Asian-Americans, little has been published on the specific manifestations, sequelae, and treatment-responsiveness of this disorder in Asian skin types. Since Asian skin types tend to be more highly pigmented than those of white people of European descent, many Asians share the predisposition toward postinflammatory hyperpigmentation seen in Africans, African-Americans and other dark-skinned peoples. It is generally assumed that the efficacy and safety of topical retinoids is the same in Asians as in white people. Tretinoin has been available in China for decades; adapalene became available in 1998. A total of 150 patients with grade II-III acne vulgaris seen at three dermatology clinics were randomized to 8 weeks of daily treatment with either adapalene gel 0.1% or tretinoin gel 0.025%. Counts of total lesions, inflammatory lesions and non-inflammatory lesions were made at baseline and again at treatment weeks 2, 4, 6 and 8. Global assessment ratings, based on percent lesion reduction from baseline were also made. Erythema, burning, pruritus, scaling and dryness were rated on a 0-3 severity scale. A total of 139 patients completed the efficacy evaluation, and 144 patients completed the safety evaluation. Both adapalene and tretinoin produce dramatic reductions in total, inflammatory and non-inflammatory lesion counts, in the range of 69-74% on average. More than 70% of patients in both groups had complete clearance or marked improvement. In general, irritation was mild, but was both more common and more severe in the tretinoin group vs. the adapalene group. No systemic side effects were seen. Adapalene offers comparable efficacy to tretinoin, but is less irritating. It represents a good alternative for the treatment of mild to moderate acne vulgaris in Chinese patients.
Background: A formulation containing agents affecting the non-inflammatory as well as the inflammatory lesions of acne vulgaris at the same time would be efficient, probably showing a high efficacy and possibly a considerable shortening of the duration of treatment. One single formulation would simplify drug administration thereby enhancing patient compliance and possibly leading to improved therapeutic results. In two studies this seems to have been corroborated for the fixed clindamycin phosphate-tretinoin gel formulation. Objective: This study was designed to assess whether the recently developed fixed formulation of 1.2% clindamycin phosphate and 0.025% tretinoin in a gel base (Velac), further referred to as Clindamycin phosphate Tretinoin Gel is at least as effective as a proprietary 0.025% tretinoin gel formulation (Aberela, Janssen Cilag Ab, Sollentuna, Sweden; further defined as tretinoin) showing an additional anti-inflammatory effect in the treatment of moderate to severe acne vulgaris. Methods: In a double-blind, randomised study 72 patients were treated with CTG and 73 with tretinoin gel in a once daily regimen for 12 weeks. Responses, irritation as well as possible systemic and other adverse effects were recorded after 4, 8 and 12 weeks of treatment and the improvement, compared to baseline, assessed in all included patients. An additional assessment of the safety parameters was carried out at week 2. Parameters of efficacy were the various acne lesion counts, the overall acne severity grade and the calculated totals of acne lesion counts. Results: CTG was statistically significantly more effective than tretinoin at the P = 0.05 level in the papular and the total mean inflammatory lesion counts as well as in the estimated or calculated mean overall acne severity scores. CTG and tretinoin gel were equally effective in the remaining parameters: open and closed comedones, the calculated total mean comedone, the pustule as well as the nodule lesion counts. The onset of action was faster for CTG than for tretinoin gel and evident in all assessed parameters except in open comedone lesion counts. In the calculated total mean acne lesion counts, half of all acne lesions had disappeared by week 6 of treatment with CTG, whereas this was recorded at week 9 for tretinoin gel. No clinically relevant changes in the parameters of safety as a consequence of treatment were observed, although the burning component of irritation was shown to be significantly less for CTG than for tretinoin gel. The observed adverse effects were considered minor. Treatment had to be discontinued in five patients on CTG and three on tretinoin. Conclusion: The addition of clindamycin to tretinoin, as in CTG, enhances the comedolytic efficacy of tretinoin in moderate to severe acne of the face, maintaining at the same time its anti-inflammatory efficacy thus accelerating resolution of all types of acne lesions without affecting the safety of response to both components.
Rational healthcare decision-making based on clinical and economic evidence is essential to provide the best possible care for patients with atopic dermatitis (AD). To evaluate treatment outcomes, resource use and cost associated with twice-weekly tacrolimus 0.03% ointment treatment vs. standard flare-only therapy in children with moderate-to-severe AD. In a pan-European, Phase III multicentre randomized clinical trial, children with mild-to-severe AD were randomized to 0.03% tacrolimus ointment or vehicle twice weekly for 12 months. Disease flares were treated using open-label tacrolimus 0.03% ointment twice daily. Clinical efficacy data were evaluated in a subgroup of 153 children with moderate-to-severe AD, with resource use data--collected prospectively using caregiver questionnaires--available from 146 children. Pooled costs of resource use were determined using German unit cost data. Direct and indirect costs were considered from third-party payer, patient and caregiver, and societal perspectives. Twice-weekly tacrolimus ointment reduced the number of flares compared with standard therapy (P < 0.001) and prolonged time to first flare (146 vs. 17 days, P < 0.001). Mean +/- SD annual costs per patient for standard and twice-weekly therapy respectively were 2002 euro +/- 2315 vs. 1571 euro+/- 1122 for severe AD and 1136 euro +/- 1494 vs. 1233 euro +/- 1507 for moderate AD. In children with AD, twice-weekly treatment with tacrolimus 0.03% ointment reduces the number of flares and prolongs time spent free from flares with no additional cost in children with moderate AD, and may be cost-saving in those with severe AD.
Many therapeutic modalities have been suggested for treatment of the chronic hand eczema. Despite good immediate efficacy of some of these treatments, there is high recurrence of the dermatitis following cessation of the treatment. Regarding the beneficial effects of the zinc sulfate on the skin, we designed a double blind study to evaluate the efficacy of the '0.05% Clobetasol + 2.5% zinc sulphate' cream versus '0.05% Clobetasol alone' cream in the treatment of the chronic hand eczema. This study was a double-blind, right to left, prospective, clinical trial. In total, 47 patients with chronic hand eczema admitted to dermatology center of Isfahan University of Medical Sciences were selected and their right hand or left hand were selected at random to be treated with either the '0.05% Clobetasol + 2.5% zinc sulphate' cream or '0.05% Clobetasol alone' cream twice daily for 2 weeks. All of the patients were treated for 2 weeks and were followed up at weeks 2, 4, 6 and 8 after starting the treatment. For determining the severity of chronic hand eczema, we assessed and scored 4 different characteristics of the lesions including redness; scaling; lichenification and pruritus. The data were analyzed using SPSS program (release 13) and statistical tests including Mann-Whitney test. Overall, 47 patients (94 samples) were evaluated. All of these patients had similar and symmetrical lesions on their right and left hands. Out of them, 35 patients were females and 12 patients were male. In all of the evaluated characterisitics, the '0.05% Clobetasol + 2.5% zinc sulphate' cream was more effective than '0.05% Clobetasol alone' cream (P < 0.05). The recurrence rate of eczema was significantly lower in the group treated with this combination treatment (P < 0.05). With regard to the encouraging results of the combination treatment with Clobetasol + zinc sulphate, we suggest that in a more extensive clinical trial, the efficacy of this treatment against chronic hand dermatitis be evaluated. In addition, evaluation of this combination therapy against other inflammatory dermatosis seems to be logical.
No single effective topical treatment is available for treating all pathogenic factors causing acne vulgaris (AV). Salicylic acid (SA), tretinoin (all-TRA) and clindamycin phosphate (CDP) are known to to be effective agents depending on their comedolytic and anti-inflammatory properties. To compare the efficacy and tolerability of SA and CDP combination (SA+CDP) with all-TRA and CDP (all-TRA+CDP) in patients with mild to moderate facial AV. Forty-six patients aged between 18 and 35 years were enrolled in a 12-week prospective, single-blind, randomized and comparative clinical study. Efficacy was assessed by lesion counts, global improvement, quality of life index and measurement of skin barrier functions. Local side effects were also evaluated. Both combinations were effective in reducing total lesion (TL), inflammatory lesion (IL) and non-inflammatory lesion (NIL) counts and showed significant global improvement as evaluated by the investigator. At the end of the study, there was no significant difference between the two groups in terms of all lesion counts. In addition, TL counts decreased faster in the all-TRA+CDP group compared with those in the SA+CDP group, with a significant difference between the two groups occurring as early as 2 weeks. Safety evaluations demonstrated that the incidence of mild to moderate side effects generally peaked at week 2 and declined gradually thereafter. Both combinations did not have an effect on stratum corneum hydration, although skin sebum values decreased with SA+CDP treatment. Combination of SA+CDP and all-TRA+CDP was effective in decreasing lesion counts and well tolerated with minimal local cutaneous reactions in patients with mild to moderate AV.
Safety and clinical effectiveness of clobetasol-17 propionate 0.05% shampoo have been shown in patients with scalp psoriasis. First, to evaluate treatment satisfaction, user convenience safety and effectiveness of clobetasol-17 propionate 0.05% shampoo treatment in daily clinical practice. Second, to identify subgroup variables that may predict treatment success or failure. A total of 56 patients with scalp psoriasis were treated with short-contact clobetasol-17 propionate 0.05% shampoo once daily for 4 weeks. Data on treatment satisfaction, user convenience, safety and effectiveness were assessed on a 7-point Likert scale using postal questionnaires. Subgroup analyses were performed to identify variables that may predict treatment outcome. A total of 41 patients returned both questionnaires (73%). Positive treatment satisfaction and user convenience were reported by 66% and 79% of patients respectively. Patient-rated indicators for disease severity improved by 39-46% (P < 0.05%). No major side-effects were reported. Subgroup analyses did not reveal any statistically significant patient variable that may predict treatment outcome. However, a tendency towards improved treatment satisfaction was observed in patients who had received fewer topical antipsoriatic treatments previously (P > 0.05). Short-contact treatment with clobetasol-17 propionate 0.05% shampoo has high user convenience and patient satisfaction rates. Moreover, the treatment is well-tolerated and efficacious from patients' perspective. Subgroup analyses did not reveal factors predicting treatment outcome, although treatment success tended to be more evident in patients who had received fewer treatments previously.
Clobetasol propionate shampoo is effective and safe in treatment of scalp psoriasis (SP). Gene expression profiling of psoriatic skin biopsies led to the identification of numerous disease-related genes. However, it remained unknown whether the gene expression profile of hair follicles of SP patients was also affected. To determine whether psoriasis-related genes are differentially regulated in the hair follicles of SP patients and whether the modulation of these genes can be correlated with clinical severity scores. A single arm, open study was conducted in three centres. SP patients received daily treatment with clobetasol propionate shampoo. At Baseline, Weeks 2 and 4, investigators assessed clinical severity parameters and collected scalp hair follicles in anagen phase. Total RNA extracted from hair follicles was used to determine the expression level of 44 genes, which were reported previously to be upregulated in the skin of psoriasis patients. RNA of good quality and sufficient quantity was obtained from hair follicles of psoriasis patients and healthy volunteers (HV). The expression level of 10 inflammation-related genes was significantly increased in psoriatic hair follicles. The patient's exploratory transcriptomic score, defined as the mean fold modulation of these 10 genes compared with HV, correlated with clinical severity scores. Clobetasol propionate shampoo was effective in decreasing both the exploratory transcriptomics and the clinical severity scores. Hair follicles of SP patients are affected by the inflammatory process. The change in the expression level of inflammation-related genes correlates with the severity of the disease.
Corel Draw's grid used for objective assessment of repigmentation.
Among all the topical immunomodulators, vitiligo's mainstay therapy includes topical corticosteroids. Many other non-immune theories have also been suggested for vitiligo's pathogenesis, but the role of oxidative stress has gained more importance in recent years. To compare the effect of topical 0.05% betamethasone vs. catalase/dismutase superoxide (C/DSO). Randomized, matched-paired, double-blind trial. Dermatology Section, University of Antioquia, Medellín, Colombia. Patients (aged > 18 years or between 12 and 18 years) with parent's informed consent, with stable or active bilateral vitiligo. Topical 0.05% betamethasone or C/DSO. Two lesions similar to each other in size were chosen. All assessments were made by two blinded investigators, and photographs were subjected to morphometry analysis. Skin repigmentation by digital morphometry. Twenty-five patients were enrolled in the study (21 women and 4 men). Mean age of participants was 40 years (range: 12-74 years). One patient on C/DSO experienced a mild local erythematous papular rash that self-resolved. At 4 months of therapy, there was no statistical difference on the percentage of repigmentation between betamethasone and C/DSO (5.63% +/- 27.9 vs. 3.22% +/- 25.8, respectively, P = 0.758). After 10 months of therapy, the percentage of skin repigmentation increased to 18.5 +/- 93.14% with betamethasone and to 12.4 +/- 59% with C/DSO, but again, we found no statistical differences (P = 0.79). Few studies have described objective methods to evaluate repigmentation among vitiligo patients. Digital morphometry provides an objective assessment of repigmentation in vitiligo. Objective vitiligo repigmentation with topical C/DSO at 10 months is similar to topical 0.05% betamethasone. Although a mild adverse effect was related to the use of C/DSO, such finding was not severe enough to discontinue treatment.
Background: Clinical efficacy of topical corticosteroids in alopecia areata (AA) is still controversial. Positive clinical results have been obtained using ointments with occlusive dressing but this approach has a low patient compliance. Recently, a new topical formulation (thermophobic foam: Versafoam) of clobetasol propionate 0.05% has been introduced on the market (Olux, Mipharm, Milan, Italy) (CF). This formulation is easy to apply. After application to the skin the foam quickly evaporates without residues and it has a good patient compliance. In vitro studies have also shown that this formulation enhances the delivery of the active compound through the skin. Aim: To evaluate the efficacy, safety and tolerability of CF in the treatment of moderate to severe AA. Subjects and methods: Thirty-four patients with moderate to severe AA (eight men, mean age 40+/-13 years) were enrolled in a randomized, double-blind, right-to-left, placebo-controlled, 24-week trial. Alopecia grading score (AGS) was calculated at baseline and after 12 and 24 weeks of treatment using a 0-5 score (0=no alopecia; 5=alopecia totalis). Clobetasol foam and the corresponding placebo foam (PF) were applied twice a day for 5 days/week for 12 weeks (phase 1) using an intrapatient design (right vs. left). From weeks 13 to 24 each enrolled patient continued only with the treatment (both on the right and left site) that was judged to have a greater efficacy than that on the contralateral side (phase 2). The primary outcome of the trial, evaluated on an intention-to-treat basis, was the hair regrowth rate, which was evaluated using a semiquantitative score (RGS) (from 0: no regrowth, to 4: regrowth of 75%). Results: At baseline the AGS was 4.1 (range: 2-5). Nine (26%) patients prematurely concluded the trial. At the end of phase 1, a greater hair regrowth was observed in 89% of the head sites treated with CF vs. 11% in the sites treated with PF. The RGS was 1.2+/-1.6 in the CF-treated sites and 0.4+/-0.8 in the PF-treated sites (P=0.001). A RGS of 2 (hair regrowth of more than 25%) was observed in 42% CF-treated sites and in 13% of PF-treated sites (P=0.027). In seven subjects (20%) a RGS of 3 to 4 (hair regrowth of 50%) was observed in CF-treated sites. In three subjects (9%) a RGS of 4 (hair regrowth of 75%) was observed in CF-treated sites. In one patient only, in a PF-treated region, a RGS of 3 was observed. The AS was reduced to 3.8 by CF treatment at the end of phase 1 and to 3.3 at the end of phase 2 (P=0.01). From weeks 12 to 24 the treatment with CF induced a further increase in the RGS (from 1.2 to 1.5+/-1.4). Forty-seven per cent of CF-treated patients had a RGS of 2 at the end of the trial. A total of eight patients (25%) at the end of the treatment with CF showed a RGS of 3. Folliculitis occurred in two patients. No significant modifications in cortisol and ACTH blood levels were observed during the trial. Conclusion: This new formulation of clobetasol propionate foam is an effective, safe and well-tolerated topical treatment for AA. This formulation has a good cosmetic acceptance and patient compliance profile.
Topical aloe vera (AV) has been used to treat various skin conditions, including psoriasis, with good results. This study aims to compare the efficacy of AV and 0.1% triamcinolone acetonide (TA) in mild to moderate plaque psoriasis. A randomized, comparative, double-blind, 8-week study was designed. Eighty patients randomly received AV or 0.1% TA cream and their clinical response were evaluated using the Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI). After 8 weeks of treatment, the mean PASI score decreased from 11.6 to 3.9 (-7.7) in the AV group and from 10.9 to 4.3 (-6.6) in the TA group. Between-group difference was 1.1 (95% confidence interval -2.13, -0.16, P = 0.0237). The mean DLQI score decreased from 8.6 to 2.5 (-6.1) in the AV group and from 8.1 to 2.3 (-5.8) in the TA group. Between-group difference was 0.3 (95% confidence interval -1.18, -0.64, P = 0.5497). There was no follow-up period after the 8-week treatment. AV cream may be more effective than 0.1% TA cream in reducing the clinical symptoms of psoriasis; however, both treatments have similar efficacy in improving the quality of life of patients with mild to moderate psoriasis.
Background Despite recent advances in the treatment of psoriasis, the therapeutic options for nail psoriasis are very limited, particularly when this is the only manifestation of the disease. Objective We performed a randomized controlled open-label study to assess the efficacy and safety of a topical treatment with tacrolimus 0.1% ointment in nail psoriasis. Methods In each patient, tacrolimus 0.1% ointment was prescribed for application only on the affected nails of a randomly selected hand for 12 weeks, whereas nails of the other hand did not receive any treatment. Severity of nail psoriasis was evaluated using the Nail Psoriasis Severity Index (NAPSI) score. Results We enrolled 21 consecutive psoriatic patients. At week 12, a statistically significant (P < 0.001) improvement was obtained in the treated hands with respect to the hands used as control (NAPSI score absolute change 13.0 and 3.0 respectively). Each of the enrolled patients concluded the period of treatment, but one patient was withdrawn from tacrolimus application after 9 weeks because of the appearance of acute paronychia. Discussion Our study showed that tacrolimus 0.1% ointment may be an efficacious and safe therapeutic opportunity in the treatment of nail psoriasis. Our data should be confirmed by a double-blind study with a larger sample of patients.
Only a few, small double-blind clinical trials have been reported for the treatment of vitiligo. Narrowband-ultraviolet B (NB-UVB) is an established form of treatment for this condition. Tacrolimus ointment is assumed to have an effect in some patients. To assess the additive effect of tacrolimus ointment (0.1%) once daily in vitiligo patients treated with NB-UVB. In a randomized double-blind trial, patients with stable symmetrical vitiligo were treated half-side with tacrolimus ointment (0.1%) and half-side with placebo ointment. Whole body NB-UVB was given twice or thrice weekly for at least 3 months. As a morphometric device, Visitrak(TM) was used to measure the area of the vitiligo target lesions. Of 40 patients, 27 had a better effect on the tacrolimus side. The degree of improvement was significantly better on the tacrolimus side (P = 0.005). The median reduction in the target lesion areas was 42.1% on the tacrolimus side and 29% on the placebo side. There was a correlation between the effect and the number of topical tacrolimus applications (P = 0.044), but there was no correlation with the number of UV treatments given; neither any significance of gender, age, skin type, duration of disease, familial occurrence of vitiligo nor presence of other autoimmune disease or atopy was observed. We found a significant reduction in the patients' subjective disease impact during the treatment period (P < 0.001). According to this study, the combination of NB-UVB and tacrolimus ointment (0.1%) is more effective than UV treatment alone in patients with vitiligo. The effect is tacrolimus total dose-dependent.
A 9-month-old infant, with no family history of atopy, presenting with erythematous, itchy plaques, and sleep disturbance, was diagnosed with atopic eczema (AE). Previous treatment with topical hydrocortisone and emollients had little effect. The infant was treated nightly with methylprednisolone aceponate (MPA) 0.1% (Advantan(®) ) cream, in addition to emollients and an oral antihistamine. After 1 week of once-daily MPA 0.1% treatment, followed by 1 week of alternate-day treatment with Advantan, significant improvements in AE symptoms and sleep were observed. The patient's caregiver reported overall treatment satisfaction and no side effects of Advantan. For this infant with newly diagnosed AE, Advantan improved symptoms and sleep quality in a safe and well-tolerated manner.
BACKGROUND AND OBJECTIV:E Treatment in psoriasis vulgaris continues to unmet needs in terms of efficacy, quality of life and costs. Patients with moderate forms of psoriasis are using topical corticosteroids as first-line therapy and patients with severe forms also use this therapy. Optimization of this treatment is made by the use of combination drugs or by the sequential or rotational therapies. A multicentric clinical study was performed to measure the efficiency of mometasone furoate 0.1% and salicylic acid 5% and mometasone furoate 0.1% as sequential local therapy in psoriasis. This was a randomized, multicentre trial with two patient groups receiving active treatment. The study group (N = 184) received mometasone furoate 0.1% and salicylic acid 5% for the first 7 days of treatment, and in the following 14 days, the patients used mometasone furoate 0.1%. The second group (N = 176) was treated with mometasone furoate 0.1% for 21 consecutive days. Psoriasis Area Severity Index (PASI) score and Dermatology Life Quality Index (DLQI) were calculated. After the first week of treatment in the study group, the reduction of PASI score was 44%, statistically significant greater than the reduction of PASI score in the second group (37%). Quality of life estimated by DLQI indicated significant lower values in the first (study) group. The sequential treatment mometasone furoate 0.1% and salicylic acid 5% followed by mometasone furoate 0.1% proves to be efficient, safe and an excellent option for the following sequence: in-patient and out-patient.
Guidelines identify a 3-month topical application of an ultra-potent corticosteroid ointment as the mainstay of medical treatment for vulvar lichen sclerosus (VLS). However, there are no trials providing evidence that any specific corticosteroid is superior to another. To assess the effectiveness and safety of a 12-week application of mometasone furoate (MMF) 0.1% ointment, with a tapering regimen, in achieving control of VLS signs and symptoms and to detect potential risk factors for VLS non-response. 147 patients affected with VLS were enrolled in a 12-week active treatment phase (ATP) with topical 0.1% MMF. The primary efficacy endpoint was the rate of patients achieving clinical response, as defined by protocol parameters. The secondary efficacy endpoint was to assess the changes of mean VLS-related symptoms after the 12-week ATP compared with baseline. By the end of the ATP, 113 patients (80.7%) experienced a treatment response, whereas 27 women (19.3%) were judged as non-responders. Mean symptom scores decreased significantly in the study patients, regardless of their clinical response at the end of the ATP. Among all the epidemiological and clinical data considered, only the absence of previous medical therapies was found to be related to a significantly higher risk of non-response to treatment. Application of 0.1% MMF ointment for 12 weeks on a tapering regimen was found to be an effective and safe therapy option in the ATP of VLS and could represent an alternative first-line treatment to an ultra-potent molecule.
Betamethasone valerate (BMV) is a medium-potency corticosteroid commonly used for the treatment of chronic psoriasis. Although occlusion has been shown to enhance the efficacy of BMV treatment, no ready-to-use occlusive BMV formulation is currently approved for the market. Forty-two patients with mild to moderate psoriasis and with symmetrical lesions were treated with BMV 0.1% tape and BMV 0.12% cream for 30 days in a half-side distribution. Both treatments resulted in a significant clinical improvement. Efficacy and tolerability were evaluated by comparison of pre-treatment and post-treatment psoriasis area and severity index and self-administered psoriasis area and severity index scores, and by comparison of the changes from baseline in clinical appearance and hydration. Lesions treated with BMV 0.1% tape showed higher reductions from baseline in the psoriasis area and severity index and the self-administered psoriasis area and severity index scores (61.7% and 59.3%, respectively), compared with lesions treated with BMV 0.12% cream (39.5% and 34.0%, respectively). No serious local or systemic treatment-related adverse effects were reported. Our results indicate a higher efficacy of BMV 0.1% tape compared with BMV 0.12% cream in the treatment of mild to moderate chronic plaque psoriasis.
Tacrolimus inhibits T-lymphocyte activation and dermal Langerhans' cells, without the side-effects of corticosteroids. The safety profile of tacrolimus makes it a promising therapeutic option for dermatitis affecting the delicate periorbital skin. To access the efficacy and tolerability of tacrolimus ointment 0.1% in the treatment of allergic contact eyelid dermatitis. Twenty adults (16 women, 4 men) with eyelid dermatitis and with at least one positive patch test reaction to relevant contact allergens were treated with topical tacrolimus in a prospective, open-label, non-comparative clinical study. Dermatitis was graded at baseline, at day 30 and day 60, using a 4-point grading system for the following parameters: erythema, oedema, scaling, lichenification, fissuring (investigator assessment) and burning/stinging and pruritus (patient assessment). All patients completed the study. Erythema, oedema, scaling and lichenification showed improvement from baseline to 30 days of treatment ( P < 0.001), but fissuring was not significantly affected. At 60 days, no further improvement of these investigator parameters was observed. Patient parameters improved significantly by day 30 ( P < 0.004) and there was a trend for further improvement at the end of 60 days (for burning, P = 0.046; for pruritus, P = 0.059). Ten per cent of patients mentioned burning and itching, at the application site, during the first days of treatment. No other adverse events were observed. Topical tacrolimus is a promising alternative in patients with allergic contact eyelid dermatitis. Therapy was effective by 1 month and was well tolerated. These preliminary results merit a larger, controlled, study.
Microcomedones representing the clinically non-visible central precursor lesions of acne are induced by sebaceous hyperplasia as well as altered follicular growth and differentiation, and evolve into both comedones and inflammatory lesions. Thus, targeting microcomedone formation is essential in the prevention and therapeutic control of acne. The aim of this study was to assess the capacity of adapalene gel, 0.1%, to control the number of microcomedones after a combination treatment followed by a maintenance treatment. This was a single-site exploratory study in subjects with a diagnosis of mild to moderate acne vulgaris and the presence of at least 250 microcomedones per cm(2) at screening visit, counted via cyanoacrylate strips (CyASt). During the first 8 weeks, a combination of adapalene gel (0.1%) and benzoyl peroxide gel (2.5%) was applied. During the randomized, investigator-blinded, and vehicle-controlled 12-week maintenance phase, adapalene once daily (QD), or adapalene alternately with its vehicle once daily every other day (QoD), or vehicle QD were applied to the face. CyASt sampling on the forehead was done at baseline, week 8, and week 20. Lesion counting allowing calculating a defined success rate was done at all visits. A total of 54 subjects entered the combination phase, and 49 subjects were randomized into the maintenance phase: 16 in both the adapalene QD and the QoD group and 17 subjects receiving the vehicle. The microcomedone median count decreased for all groups until week 8 (end of combination phase) from 319 to 157. Microcomedone counts at the end of the maintenance phase (week 20) showed a significant percent difference (P = 0.04) between adapalene QoD (-53.5) and the vehicle (-42.1) and between adapalene QD (-50.6) and the vehicle (P = 0.037) compared with baseline. The application of adapalene gel, 0.1% monotherapy daily, or alternately every other day, significantly helps to control the microcomedone count during a 12-week maintenance treatment after a previous combination therapy with benzoyl peroxide in patients with mild to moderate acne.
A 3-year-old girl with a > 2-year history of atopic dermatitis (AD) and known egg allergy, presented with an extensive AD flare including exudative eczematous lesions and lichenification on her flexures. The patient reported intense pruritus and showed signs of scratching on her trunk, arms, buttocks and thighs. After 2 weeks of twice-daily application of methylprednisolone aceponate (MPA) 0.1% (Advantan(®) ), temporary withdrawal of emollients, and mild bathing/cleanser use, the eczematic condition was considered clear, and marked improvement of all treated lesions (including disappearance of scaling) were observed. No side effects of Advantan were reported; the patient's parents expressed a high level of satisfaction with treatment. Advantan was safe and effective in controlling a severe pruritic flare of chronic AD in a small child.
A 7-month-old infant, with no known food allergy or intolerance, presenting with eczema lesions affecting many parts of his body, was diagnosed with infantile eczema. A skin barrier defect, due to filaggrin deficiency, was suspected. Prior treatment with emollients was not effective and produced discomfort. After twice-daily application of methylprednisolone aceponate (MPA) 0.1% (Advantan(®) ), in addition to temporary withdrawal of emollients, for 10 days. At the follow-up examination, improvements in all eczema lesions, scratching behavior and sleep quality were observed, and eczema was considered almost clear and under control. Advantan was prescribed to control new flares of eczema, and heavy emollients were recommended to treat residual dryness and damage from original lesions. No side effects of Advantan were reported. In an infant with newly diagnosed eczema, Advantan was safe and effective in alleviating lesions and scratching severity and restoring sleep.
A 13-year-old girl with a 12-year history of atopic dermatitis (AD), testing positive for inhalation and foodborne allergens, presented with season-dependent, highly pruritic AD lesions and lichenification on her cheeks, trunk, forearms, and ankle joints. After immediate treatment with oral antihistamine, followed by once-daily methylprednisolone aceponate (MPA) 0.1% (Advantan(®) ) cream for the facial lesions and Advantan ointment for treatment of the trunk and extremities for 7 days, marked improvement of AD signs (e.g., redness and lichenification) was noted. Pruritus was completely alleviated. No side effects were reported for Advantan. By combining multiple formulations of Advantan, treatment was tailored to successfully treat a widespread flare in this adolescent patient with chronic AD.
Used as individual agents, topical antibiotics and benzoyl peroxide are known to be effective in treatment of acne. Clindamycin phosphate 1% with benzoyl peroxide 5% (CDP/BPO) is a new combination gel, made by rationale, in that combination drug is more effective than either ingredients used alone. Adapalene 0.1% (ADA) is the third-generation retinoid, shown to be as effective as other topical retinoid with well tolerability. To compare the efficacy and tolerability in combination of CDP/BPO in comparison with ADA in Asian patients with mild to moderate acne vulgaris. Total of 69 patients, including 31 patients for CDP/BPO group and 38 for ADA group, with mild to moderate acne vulgaris were enrolled for a 12-week prospective, randomized, open-label comparative study of topical agents. Efficacy was assessed by lesion counts, acne grading system, and global improvement. Adverse events were also evaluated in scale of 0 (none) to 3 (severe). Both CDP/BPO and ADA were effective in reducing lesion counts and acne severity scale and showed significant global improvement. However, CDP/BPO offered greater efficacy against inflammatory lesions than ADA. Both drugs were well tolerated with minimal adverse drug reactions. Combination formulation of CDP/BPO and ADA were shown to be both effective in decreasing total, inflammatory, and non-inflammatory lesion counts along with well tolerability in Asian patients with mild to moderate acne vulgaris.
Hyaluronic acid (HA) is a primary component of the extracellular matrix, and the efficacy of HA on oral ulcers is rarely reported. To observe the efficacy and safety of the topical application of 0.2% HA gel on recurrent oral ulcers and to compare its effects in patients with recurrent aphthous ulcers (RAU) and the oral ulcers of Behçet's disease (BD). Thirty-three outpatients with recurrent oral ulcers were included in the study (17 patients: BD, 16 patients: RAU). The patients used topical 0.2% HA gel twice daily for 2 weeks. The subjective parameters of patients [number of ulcers, healing period, visual analogue scale (VAS) for pain] were investigated and objective assessments (number of ulcers, maximal area of ulcer and inflammatory signs) were inspected by a physician. A subjective reduction in the number of ulcers was observed in 72.7% of the patients. A decrease in the ulcer healing period was observed in 72.7% of the patients; 75.8% experienced improvement in VAS for pain. Objective inspection of the ulcers showed a reduction of numbers in 57.6% of the patients, and 78.8% of the ulcers showed a decrease in area. Among the inflammatory signs, swelling and local heat were significantly improved after treatment. No significant differences were found between the BD group and RAU group in subjective and objective parameters, except for inflammatory signs. No side-effects were observed. The topical application of 0.2% HA gel seems to be an effective and safe therapy in patients with recurrent oral ulcers; the study supports the use of HA in BD with oral ulcers.
Increasing antibiotic resistance of Propionibacterium acnes and growing awareness on the side effects of topical and systemic drugs in the treatment of acne vulgaris by physicians and patients have paved the way for a search into new efficacious and safe treatment modalities such as photodynamic therapy (PDT). Although the efficacy of PDT using 20% 5-aminolevulinic acid (ALA) cream has been established, phototoxic side effects limit its use. The 5-ALA concentration can be lowered by a factor of 40 by changing the vehicle of 5-ALA from a moisturizing cream to liposome encapsulation. Assessment of the efficacy and the safety of PDT using 5-ALA 0.5% in liposomal spray and intense pulsed light (IPL) in combination with topical peeling agents (Li-PDT-PC) in acne vulgaris. 32 patients suffering from acne participated in this randomized, prospective, single blind study. All patients were treated with Li-PDT-PC. During the study nine patients were additionally treated with topical or systemic antibiotics (Li-PDT-PC-AT). These patients were removed from the study although their results were recorded. Results After a mean period of 7.8 months and a mean number of 5.7 treatments the mean total number of lesions dropped from 34.6 lesions to 11.0 lesions, resulting in a mean improvement of 68.2%. Side effects were minimal. Additionally, an intention to treat analysis was conducted. Photodynamic therapy of acne vulgaris using 5-ALA 0.5% liposomal spray and IPL in combination with topical peeling agents is safe and efficacious, even in patients with acne recalcitrant to standard therapy.
Recently, two placebo-controlled studies have shown that topical metronidazole was effective in the treatment of seborrheic dermatitis. To compare the efficacy and safety of metronidazole 0.75% gel with that of ketoconazole 2% cream in the treatment of facial seborrheic dermatitis. A total of 60 consecutive patients with facial seborrheic dermatitis were included. Patients were randomized into two groups. One group used ketoconazole 2% cream with metronidazole gel as vehicle; the other group used metronidazole 0.75% gel with ketoconazole cream as vehicle for a 4-week treatment period. Main outcome measures were change in clinical severity scores, patients' and investigator's global evaluation of improvement and frequency of side-effects. All the assessments were made by an investigator who was unaware of which group the patients were allocated to. Mean percentage decrease in clinical severity scores from baseline to last available visit was 63.4% (95% CI 57.7-69) and 54.4% (95% CI 47.9-61) in the ketoconazole- and metronidazole-treated patients, respectively (P = 0.31). Eighty-two per cent of patients in the ketoconazole group vs. 79% of patients in the metronidazole group rated their global improvement as significant or moderate (P > 0.05). No statistically significant difference in the frequency of side-effects was detected between the two groups. The results of this study need to be confirmed in further studies involving large numbers of patients. Our data demonstrated that metronidazole 0.75% gel had a comparable efficacy and safety profile with that of ketoconazole 2% cream in the treatment of facial seborrheic dermatitis.
Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. We previously reported that the prognosis of MF patients is not only related on clinical variables but it is also associated with peculiar HLA alleles. Until today, the association of HLA ligands for KIR with the prognosis of the disease has not yet been analysed. We investigated the frequency of HLA ligands for killer cell Immunoglobulin-like receptors (KIRs) in MF patients, evaluating if the presence of particular HLA alleles that are ligands for KIR may have prognostic value. The study includes 46 Caucasian MF patients that, between 1993 and 1997, underwent HLA genomic typing. All patients were diagnosed and followed up from 1977 to 2012 (mean follow-up of 11 years). MF patients have been divided into two groups (long survivors and dead patients). We noticed that the HLA-Bw6/Bw6 specificity increased among the group of seven dead patients compared to the group of 39 long survivors (71.4% vs. 41.0%, P = ns, OR = 3.59), while in the long survivors group the HLA- Bw4/Bw4 specificity increased when compared to dead patients (23.0% vs. 0%, P = ns). Moreover, we observed that six of the seven dead patients had HLA-DQB1*05; the phenotypic frequency of this HLA allele, in dead and long survivors patients, was 85.7% and 23.0% respectively (P = 0.004; OR = 20). Our observations suggest that the presence of the HLA-DQB1*05 alleles characterizes the patients with the poorest prognosis in MF. In addition, absence of the KIR-ligand epitope HLA-B Bw4 showed a trend of being more prominent in MF patients with the poorest prognosis. © 2015 European Academy of Dermatology and Venereology.
Human leucocyte antigen (HLA)-II alleles have been found to be associated with vitiligo in different populations, and several studies also suggested that HLA class II alleles/haplotypes were associated with a different type vitiligo. Of HLA class II alleles, DRB1*07 has consistently shown a positive association with vitiligo in Chinese Han population. To further explore the relationship between DRB1*07 and vitiligo and to evaluate the DRB1*07 effect on the clinical features of vitiligo in Chinese Han population. This study investigated DRB1*07 allele distribution in 1178 unrelated Chinese vitiligo patients and 1743 healthy controls using polymerase chain reaction/sequence specific primer method and observed clinical differences between DRB1*07 positive and DRB1*07 negative patients. The analysis of the 1178 cases and 1743 controls revealed a highly association between DRB1*07 allele and vitiligo [odds ratio (OR) = 1.97, P = 2.13 × 10(-17) ]. DRB1*07 positive patients had early disease onset (OR = 1.49, P = 0.001), higher frequency of family history (OR = 1.44, P = 0.006) compared with DRB1*07 negative patients. The DRB1*07 showed significant association with vitiligo in the study population. This study confirmed that DRB1*07 positive patients had some obvious clinical differences from DRB1*07 negative patients in the Chinese Han population.
Atopic dermatitis (AD) and psoriasis are chronic skin conditions. Local or systemic treatments are effective, but their effects are transient. Hydrotherapy, used alone or in combination with other treatments, could be considered as one form of care in providing effective management of these dermatoses. The objective of this observational study was to evaluate the benefit of a 3-week treatment at Avène Hydrotherapy Centre in a very large cohort of patients suffering from atopic dermatitis and psoriasis and to assess the treatment benefits on patients undergoing hydrotherapy for two consecutive years. This 8-year observational study analysed 14,328 records of patients having a dermatological disease and who came to Avène Hydrotherapy Centre for a 3-week treatment between 2001 and 2009. Among them, patients were suffering from atopic dermatitis (n = 5916) and psoriasis (n = 4887). On admission on D0 (day 0) and at the end of cure on D18 (day 18), the severity of AD and psoriasis were evaluated by SCORing Atopic Dermatitis (SCORAD) and Psoriasis Area and Severity Index (PASI), respectively. In order to assess the cumulative effect of the hydrotherapy treatment, the evolution of SCORAD or PASI of patients who came 2 years in a row was also calculated. A significant improvement in SCORAD was observed between D0 and D18 (-41.6%) (P < 0.0001) and similarly, a significant reduction in PASI was noted between D0 and D18 (-54.4%) (P < 0.0001) after 3-weeks of hydrotherapy. PASI 50 and PASI 75 were 64.3% and 19.5%, respectively. For atopic patients (n = 1102) or patients suffering from psoriasis (n = 833) who came for two consecutive years, a significant SCORAD and PASI improvement was observed on D0 of the second year when compared with D0 of the previous year (P < 0.0001). This study is the first observational study in such a large cohort demonstrating the benefit of a 3-week treatment at the Avène Hydrotherapy Centre for atopic and psoriatic patients.
Skin cancer screening aims to detect potentially metastasizing skin cancers at an early and surgically curable stage. This may take the form of mass screening, as currently occurs in Germany, or of targeted screening of those at greatest risk. To develop a model to identify patients at high risk of developing skin cancer who would benefit from regular skin cancer screening. This was an open prospective point-prevalence study of consecutive patients presenting to dermatologists for a total skin check. Demographic and skin cancer risk factors were recorded and, for the first time, histology of skin lesions was documented. Results were analysed by univariate and multivariate analyses and, after logistic regression with stepwise forward selection, a risk-group model was developed. The results of 108,281 total skin examinations were available for analysis. 142 definite melanomas, 108 severely dysplastic naevi/cannot-exclude-melanoma, 491 basal cell carcinomas (BCC) and 93 squamous cell carcinomas (SCC) were excised. A risk model was developed for melanoma and SCC based on mathematical e-functions. The model had >92% sensitivity for melanoma and SCC and an overall 67.24% specificity for melanoma, SCC and BCC. This targeted risk model identified one-third of the study population as being at risk for the development of melanoma and SCC. Using the risk calculator developed from this study, targeted screening of the identified at-risk population reduces the numbers needed to be screened regularly by 50%, yet has better sensitivity for melanoma and similar sensitivity for SCC compared to the current mass screening programme in Germany.
Background There is a need for the development of novel non-steroidal topical drugs for the treatment of psoriasis. Objective To assess the efficacy and safety of topical 1.0% WBI-1001 in patients with mild to moderate plaque psoriasis. Methods A total of 61 patients with 1–10% body surface area (BSA) covered with plaque psoriasis and a physician’s global assessment score (PGA) of 2–4 were randomized (2 : 1) to receive either 1% WBI-1001 in a cream formulation or placebo, applied twice daily for 12 weeks. Efficacy was evaluated using PGA, BSA and Psoriasis Area and Severity Index (PASI). The primary endpoint was the change from baseline (Day 0) in PGA at week 12. Results The improvement in PGA at week 12 was 62.8% for patients randomized to WBI-1001 when compared with 13.0% for patients randomized to placebo (P < 0.0001). At week 12, the proportion of patients who achieved a PGA of clear or almost clear and the mean improvement in BSA were 67.5% and 79.1%, respectively, for patients randomized to WBI-1001, when compared with 4.8% (P < 0.0001) and an increase of 9.4% (P < 0.0001), respectively, for patients randomized to placebo. More application site adverse drug reactions were observed in patients randomized to WBI-1001 than in those randomized to placebo. These adverse drug reactions were all mild or moderate in intensity. Conclusion Topical WBI-1001 induces rapid and significant improvement in patients with plaque psoriasis.
Background Cutaneous mastocytosis (CM) is a typical presentation of mastocytosis in children. However, systemic mastocytosis may also occur in children. Objective We tried to characterize the clinical features of childhood-onset mastocytosis and estimate the value of the SCORMA (SCORing Mastocytosis) Index and serum tryptase levels as disease severity parameters. Methods In a survey of 101 children mastocytosis was diagnosed and classified according to World Health Organization criteria. In all the cases serum tryptase levels and the SCORMA Index were done to assess the extent and intensity of the disease. Results Cutaneous mastocytosis was diagnosed in 100 children; 84% of them presented maculopapular CM, 10% mastocytoma and 6% diffuse cutaneous mastocytosis. Moreover, systemic mastocytosis with bone marrow infiltration and associated with maculopapular CM was found in one case. There was a positive correlation of serum tryptase level to the SCORMA Index. Both the mean tryptase level and the mean SCORMA Index were elevated in diffuse cutaneous mastocytosis children when compared with other forms CM. A significantly higher mean tryptase level was found in children with flushing, hypotension, diarrhoea, extensive bullous lesions and osteoporosis or osteopenia. Conclusion Mastocytosis in children usually has a benign course. Nevertheless, severe mediator-related symptoms and systemic involvement may appear. Therefore, a multidisciplinary approach involving careful monitoring of the serum tryptase level, SCORMA Index and the organ function is recommended. Both tryptase levels and the SCORMA Index are of a great value as disease severity parameters and they should be assessed simultaneously in all mastocytosis patients.
Objective The aim of the presented prospective study was to use a digital dermatoscopic system to follow-up patients with multiple melanocytic naevi, and to evaluate the frequency and character of dermatoscopic changes. Methods We monitored selected melanocytic lesions with the use of a 6-month follow-up interval between check-ups. We searched for changes in size, shape, symmetry, structure and colour. We defined the criteria for surgical excision and histopathological examination of changing lesions. We created a small group of excised unchanged atypical melanocytic naevi. Results We completed dermatoscopic monitoring of 1027 melanocytic lesions in 121 patients at risk of developing malignant melanoma. The average total follow-up interval was 21.0 months. We noticed a substantial enlargement of monitored lesions in 4.5% of cases, and there was a change of shape in 1.3% and change of asymmetry in 2.0%. The appearance of new structures, frequently being associated with malignant melanoma, was observed in 10 lesions, and it was predictive for the histopathological confirmation of this diagnosis in all cases. About 80% of monitored lesions remained unchanged. We excised 38 monitored lesions (seven melanomas in situ, four thin invasive melanomas and 27 melanocytic naevi). There was no melanoma excised in the group of unchanged atypical melanocytic lesions. Conclusion Digital dermatoscopic follow-up facilitates the recognition of thin malignant melanomas and helps to reduce the number of unnecessary excisions.
Genetic factors that predispose individuals to Behçet's disease (BD) and periodontal disease. Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of both BD and periodontal disease. The relationship with periodontitis and the pathogenesis of BD has not yet been determined. The aim of the present study was to investigate the possible relation of the periodontal scores and single nucleotide polymorphism of TNF-alpha-1031T/C with BD compared with healthy controls (HC) and recurrent aphtous stomatitis (RAS). We also sought to determine the effects of periodontal condition and TNF-alpha-1031T/C polymorphism on clinical severity of BD. Eighty-two unrelated patients with BD, 42 RAS patients and 77 HC were enrolled in the study. Periodontal status of all subjects was evaluated according to the World Health Organization community periodontal index of treatment needs (CPITN). For genotyping, polymerase chain reaction-restriction fragment length polymorphism was employed. The mean CPITN was observed to be higher in patients with BD compared with HC and RAS (P < 0.001). TNF-alpha-1031C allele was significantly higher in patients with BD (P = 0.023) and RAS (P = 0.007) compared with HC. Mean CPITN was higher in CC genotype compared with other genotypes (P = 0.004). Moreover, CPITN and CC genotype was found to be correlated with the severity of the disease. Our data indicate that the TNF-alpha-1031T/C gene polymorphism (CC genotype) is a risk factor for periodontitis, RAS and BD patients and also suggests that long-term periodontal follow-up and education of oral hygiene in patients with BD may help to prevent the development and/or progression of the disease.
Top-cited authors
Carle F Paul
  • Paul Sabatier University - Toulouse III
Christos C. Zouboulis
  • Städtisches Klinikums Dessau, Medizinische Hochschule Brandenburg Theodor Fontane
Denis Jullien
  • Hospices Civils de Lyon (Centre Hospitalier Universitaire de Lyon)
François Aubin
  • University of Franche-Comté
Brigitte Dreno
  • University of Nantes