Acta Dermato-Venereologica

Published by Society for Publication of Acta Dermato-Venereologica
Online ISSN: 0001-5555
Tazarotene and calcipotriol are both effective in the treatment of psoriasis. An investigator-blind, bilateral comparison of 44 lesion pairs in 19 patients was conducted to evaluate the efficacy, side effects and duration of therapeutic effects of once-daily tazarotene 0.1% gel plus petrolatum with twice-daily calcipotriol 0.005% ointment in plaque psoriasis. It consisted of a 12-week treatment phase, followed by a 4-week post-treatment observation phase. At the end of the treatment phase, tazarotene-petrolatum was as effective as calcipotriol in both objective and subjective overall efficacy assessment. Calcipotriol had a significantly greater effect in reducing erythema than tazarotene-petrolatum at weeks 2-8. At week 16, tazarotene-petrolatum demonstrated a significantly better maintenance effect in all parameters. Local irritation was noted only in tazarotene-petrolatum-treated lesions. Once-daily tazarotene 0.1% gel plus petrolatum was as effective as twice-daily calcipotriol 0.005% ointment in the treatment of plaque psoriasis, but had a better maintenance effect after the cessation of therapy.
t azarotene 1.13 (0.88) 0.28 (0.45) 0.97 (0.71) Clobetasol 1.09 (0.99) 0.36 (0.48) 0.97 (0.85) Onycholysis t azarotene 1.97 (1.27) 0.82 (0.73) 1.54 (1.00) Clobetasol 1.90 (1.28) 0.82 (0.62) 1.73 (1.09) Hyperkeratosis t azarotene 1.80 (1.04) 0.36 (0.48) 0.97 (0.80) Clobetasol 1.70 (0.95) 0.58 (0.66) 1.56 (0.83) Salmon patches t azarotene 1.15 (0.89) 0.17 (0.38) 0.69 (0.72) Clobetasol 1.07 (0.78) 0.19 (0.45) 0.85 (0.61)
In an open trial, including 54 boys with phimosis, treatment with clobetasol propionate cream (Dermovate, Glaxo, UK) was shown to be effective, without side effects. Surgery, the treatment of choice in many centres, was avoided in 70% of the patients.
Median percentage affected total body surface area (BSA) between visit at day 1 and month 24. LoCF: Last observation Carried Forward.  
Prevalence of herpes simplex during the study. M: month.  
Atopic dermatitis often requires long-term treatment. This European, multicentre, non-comparative, 24-month, follow-up study investigated the efficacy and safety of 0.1% tacrolimus ointment applied to adults with atopic dermatitis. Patients (n=672) applied a thin layer of 0.1% tacrolimus ointment twice daily for 3 weeks to all affected body areas. After 3 weeks, ointment was applied once daily. Clinical improvement became apparent after 2 weeks of treatment and 65.5% of patients had a rating of clearance, excellent or marked improvement by month 3. Skin burning (31.7%) was the most common causally-related adverse event, followed by pruritus (11.3%) folliculitis (6.4%), alcohol intolerance (5.7%), herpes simplex (5.7%), skin infection (4.6%), skin erythema (3.3%) and hyperaesthesia (2.4%). The most commonly reported infections were flu syndrome (12.9%), skin infection (9.8%), folliculitis (7.4%) and herpes simplex (7.0%). Long-term treatment up to 24 months with 0.1% tacrolimus ointment is safe and efficacious in adults with atopic dermatitis.
Lichen sclerosus is a chronic relapsing disease, usually treated with ultra-potent corticosteroids. As immunological alterations are considered important aetiopathogenetic factors in lichen sclerosus, the new immunomodulating topical agents, such as tacrolimus and pimecrolimus, have been employed sporadically as alternative therapies. The aim of this study was to evaluate the therapeutic effects of tacrolimus 0.1% ointment in lichen sclerosus in 11 patients unresponsive or poorly responsive to previous treatments. Tacrolimus 0.1% ointment was applied twice daily for 6 weeks, then tapered over a further 6 weeks. Symptoms and objective parameters were evaluated and quantified at the start, after 6 weeks, at the end of the topical treatment, and at follow-up visits. Improvement or remission of symptoms was observed in the patients who completed the study, while objective parameters were poorly influenced and often were not related to symptom behaviour. Topical tacrolimus can be considered an alternative treatment for lichen sclerosus.
Study design. SD: seborrhoeic dermatitis.  
The effectiveness of intermittent topical tacrolimus to prevent relapse in patients with stabilized facial seborrhoeic dermatitis has not been evaluated. The aim of this study was to determine whether proactive use of 0.1% tacrolimus ointment can keep adult facial seborrhoeic dermatitis in remission. A total of 75 patients who had stabilized facial seborrhoeic dermatitis after 2 weeks' (open-label induction) treatment with 0.1% tacrolimus were randomized in a double-blind fashion to treatment with 0.1% tacrolimus once a week, twice a week, or vehicle twice a week, for 10 weeks (maintenance). Significant improvement in erythema, scaling and pruritus compared with baseline was maintained during the maintenance phase in both tacrolimus groups, but not in the vehicle group. The mean recurrence rate according to global assessment was significantly higher in the tacrolimus once-weekly group than in the twice-weekly group. In conclusion, twice-weekly treatment with 0.1% tacrolimus ointment had superior effects in keeping facial seborrhoeic dermatitis in remission.
Topical tacrolimus was recently introduced as a novel therapeutic option in vitiligo. Excellent results were seen mainly on the face and neck areas. We treated 30 adult vitiligo patients with tacrolimus 0.1% ointment twice daily, and compared the results with those of placebo ointment. In 20 patients, defined areas on the right arm or leg were occluded overnight with 3 different dressings. Repigmentation was evaluated quantitatively and qualitatively. Quality of life changes were assessed with the Dermatology Life Quality Index. After 6 months, treatment was stopped in 7 of 30 patients as they did not show any repigmentation, 5 of them had no occlusive therapy. After 12 months, 17 of 21 patients (81%) with facial involvement showed repigmentation of the face. Although no or minimal repigmentation occurred on the extremities when using tacrolimus ointment alone, 80% of the patients showed repigmentation on the arms when using additional occlusive, especially hydrocolloid dressings. Hands, feet and lower legs were unresponsive. The best results were obtained in patients with long-standing vitiligo. Only minimal side-effects were noted. There was no significant elevation in tacrolimus blood levels, taking into account that occlusion was performed only on limited parts of the body. In conclusion, tacrolimus 0.1% ointment proved an effective and safe treatment option for adult patients with vitiligo. Beyond the face and neck areas, repigmentation could be achieved only by additional occlusion.
Improvement of recall antigen reactions during treatment, as shown by the Merieux score. The results are presented as box-plots with the median value represented by a line across the box, and the mean by a smaller black box. 
A one-year, randomized, double-blind study was conducted in 80 patients with atopic dermatitis treated with tacrolimus ointment or a corticosteroid regimen (hydrocortisone acetate 1% ointment for head and neck, hydrocortisone butyrate 0.1% ointment for trunk and limbs) to compare efficacy and safety, and effects on Th2-reactivity. The study was completed by 36/40 patients in the tacrolimus group, and 31/40 patients in the corticosteroid group. In both groups affected body surface area, eczema area and severity index, and transepidermal water loss decreased at months 6 and 12. Tacrolimus was superior for all efficacy scores at month 6, and in the head and neck area at month 12. Recall antigen reactivity increased at month 12 in both groups. Adverse events were reported by 40/40 patients in the tacrolimus, and by 34/40 patients in the corticosteroid group. Long-term treatment with topical tacrolimus or a corticosteroid regimen improves atopic dermatitis and recall antigen reactivity, suggesting an improvement in the Th1/Th2-balance.
A randomized, controlled study of 35 patients with active chronic psoriasis has demonstrated that 0.1% dithranol in a 17% urea cream base (Psoradrate 0.1% cream, Eaton Laboratories, U.K.) shows reduction of side effects when compared with 0.1% dithranol in Lassar's paste B.P.C., and is equally effective.
There is a demand for pain relief during photodynamic therapy. We therefore investigated the efficacy and side-effects of topical morphine gel 0.3% for pain relief during topical photodynamic therapy in a randomized, double-blind, placebo-controlled study. The study involved 28 patients with actinic keratoses or basal cell carcinomas. Each patient was treated with photodynamic therapy after superficial curettage of 2 treatment areas that were randomized to morphine gel or placebo gel. The gels were applied 15 min before illumination. Pain was assessed pre-illumination, during, and immediately after illumination, using a numeric rating scale. Skin redness was determined by reflectance spectrophotometry and the size of the treated area by protoporphyrin IX fluorescence. There were no differences between the areas according to accumulation of protoporphyrin IX (p =0.34), size of fluorescence areas (p =0.84), or skin redness (p =0.95). There was no significant pain relief of topical morphine gel compared with placebo gel (p >0.23). This negative result suggests that opioid receptors may not be involved in the pain induced by photodynamic therapy.
Median percentage change from baseline over time in local psoriasis severity index (LPSI) of the target lesion, intent-to-treat population. * =  End of treatment 
Physician’s and patient’s assessment of resonse at the target lesion at week 12 (end of treatment). 
The efficacy and safety of 0.3% tacrolimus gel and 0.5% tacrolimus cream compared with calcipotriol ointment were evaluated in adults (n = 124) with mild to moderate plaque psoriasis. Treatment was twice daily for a maximum of 12 weeks. Clinical efficacy was assessed by the percentage change in the local psoriasis severity index of a target lesion between baseline and week 12. By week 12, the median percentage changes in local psoriasis severity index of the target lesions in the tacrolimus gel, tacrolimus cream and calcipotriol groups were 55.6%, 50.0% and 58.6%, respectively (no statistically significant differences). Clinical improvement was observed after one week and increased throughout the study. Tacrolimus-treated patients experienced more application site skin burning (tacrolimus gel and cream both 31.0% versus 7.5% for calcipotriol; p = 0.011). Skin burning was mostly mild in intensity and decreased substantially after 1 week of treatment. There were no differences in the nature and incidence of infections and no clinically relevant changes in laboratory values.
The number of doubtful and contact allergy reactions found in 1397 patients when testing formaldehyde 1.0% (0.30 mg/cm 2 ) and 2.0% (0.60 mg/cm 2 ). In all, 38 patients had a doubtful reaction to 1.0%, but 17 of them reacted positively to 2.0%, as indicated by the arrow.  
Our clinical experience has suggested that the presently recommended patch-test concentration (1.0%) for formaldehyde in the baseline series might be too low. Therefore, consecutively patch-tested dermatitis patients were tested simultaneously with formaldehyde 1.0% and 2.0% (w/v) in aqua. Formaldehyde 1.0% and 2.0% were applied with a micro-pipette (15 microl) to filter paper discs in Finn Chambers (0.30 mg/cm(2) and 0.60 mg/cm(2), respectively). A total of 1397 patients with dermatitis were patch-tested. In all, 68 (4.9%) patients reacted positively to formaldehyde; 37 reacted only to 2.0%, 29 reacted to both concentrations, and 2 reacted only to 1.0%. Significantly more patients were thus diagnosed with contact allergy to formaldehyde 2.0% compared with 1.0% (p < 0.001). We detected 0.1%, 0.4%, and 29.6% irritant reactions to 1.0%, 2.0%, and 3.0% formaldehyde, respectively. We conclude that, with an optimized patch-test technique, doubling the dose per area detects significantly more contact allergies to formaldehyde, but an even higher test concentration causes too many irritant reactions to be usable.
Flow diagram. Intention-to-treat (ITT) population indicates all randomized patients who have received acitretin-narrow-band TL-01 (re- TL-01) or acitretin-psoralen plus ultraviolet A (re-PUVA) and from whom at least one post-baseline Psoriasis Area and Severity Index (PASI) score was available. Withdrawn; patients who were lost to follow-up, or discontinued study because of unsatisfactory outcome or other reasons.  
Mean Psoriasis Area and Severity Index (PASI) score in patients treated with acitretin-narrow-band TL-01 (re-TL-01) or acitretin-psoralen plus ultraviolet A (re-PUVA). AUC: area under the psoriasis severity time curves. 
Three patients before ( upper panel ) and after ( lower panel ) acitretin-narrow-band TL-01 (re-TL-01) treatment. The post-treatment photographs were taken after 8 weeks. 
The combination of retinoids with phototherapy enhances the efficacy of phototherapy and reduces the cumulative ultraviolet dose and duration of the therapy needed to treat chronic plaque psoriasis. Although TL-01 phototherapy has been used widely, there are few data about the effectiveness of the combination of acitretin with TL-01 in treatment of the disease. The aim of this study was to compare acitretin-narrow-band TL-01 phototherapy with acitretin-psoralen plus ultraviolet A (acitretin-PUVA) in psoriasis. We studied 60 patients with moderate to severe plaque psoriasis who were randomly allocated to three times weekly treatment acitretin-narrow-band TL-01 or acitretin-PUVA. The efficacy of treatments was assessed using the Psoriasis Area and Severity Index by a blinded observer. Clearance of psoriasis was achieved in 56.6% of patients treated with acitretin-narrow-band TL-01 and in 63.3% of those treated with acitretin-PUVA. All of these patients remained clear of psoriasis 3 months after finishing the treatments. Mucocutaneous side-effects, such as dry lips and mouth, were the most common complaints in both groups. In conclusion, acitretin-narrow-band TL-01 is an effective and well-tolerated treatment for moderate to severe plaque psoriasis, with a therapeutic effect equal to that of acitretin-PUVA.
There are no studies of the possible association of the human leukocyte antigen (HLA) system with lichen planopilaris (LPP). To determine whether the HLA system is associated with LPP, 40 consecutive Jewish Israeli patients with LPP (study group) and 252 volunteers (controls) were typed for DRB1*and DQB1* loci by molecular methods. Compared with controls, the study group had a significantly higher frequency of the DRB1*11 allele (62% vs. 21%, corrected p-value (pc) = 0.001) owing to increased frequencies of DRB1*11: 01 and DRB1*11: 04. The DQB1*03 allele was also expressed at a significantly higher frequency in the study group (70% vs. 33%, pc = 0.0005); specifically, the frequency of DQB1*03: 01 was increased. The majority (82.5%) of the patients were of non-Ashkenazi origin. We conclude that LPP appears to be over-represented in non-Ashkenazi Jewish patients and is associated with an increased frequency of HLA DRB1*11 and DQB1*03 alleles. These findings suggest that immunogenetic factors play a role in LPP.
This study aims to investigate associations between observed clinical parameters and known genetic risk factors of psoriasis in a well-defined prospective cohort of paediatric patients with plaque psoriasis (n = 151). Significant associations were found for paediatric-onset psoriasis with ERAP1 (p = 0.002), IL23R (p = 0.01), LCE3C_LCE3B-del (p = 0.00049) and HLA-C*06 (p = 3.15 × 10-30). Psoriasis severity was associated with the single nucleotide polymorphisms tagging IFIH1 and ERAP1 (p < 0.05). An onset before 10 years of age was associated with IL12B (p = 0.02). Nail psoriasis was more often seen in HLA-C*06-negative patients (p = 0.008). Remarkably, family history is clearly not associated with HLA-C*06 in this specific group. The large proportion of patients with a positive family history in HLA-C*06 negative patients (and the lack of correlation between the two) indicates that other genes, either alone or interaction between two or more genes, may have significant effects on heritability.
HLA-Cw6 is strongly associated with psoriasis and has been suggested to be the PSORS1 gene that confers susceptibility to early-onset psoriasis. In this study of the clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population, we typed HLA-C in a cohort of 679 patients and compared the two groups. Cw*0602-positive patients (n=345) had an earlier disease onset (p < 1 x 10(-5)), more severe disease (p < 1 x 10(-3)), higher frequency of guttate psoriasis (p < 1 x 10(-9)), more affected legs and trunk (p < 1 x 10(-5)), higher incidence of Köbner's phenomenon (p=0.005) and of trauma history (p=0.009). Cw*0602-negative patients (n= 334) had more palmoplantar pustulosis (p=0.004), nail changes (p=0.001) and scalp involvement (p=0.007). However, there was no statistically significant difference between the two groups regarding age, gender, incidence of plaque psoriasis, erythrodermic, inverse, psoriatic arthritis, and the precipitation factors stress and infection. The study showed that Cw*0602-positive patients had some obvious clinical differences from Cw*0602-negative patients in a Han Chinese population, which provides evidence for an HLA-Cw*0602-associated phenotype in psoriasis.
The PSORS1 locus in the major histocompatibility complex region on chromosome 6p21.3 contains a major predisposing factor for psoriasis for which several candidate genes have been tested. The analyses are complicated by strong linkage disequilibrium in the region and the complex genetic background of psoriasis. In the search for an alternative to HLA-C we have identified a novel gene, PSORS1C3, and characterized it with regard to psoriasis. PSORS1C3 is located approximately 7 kb centromeric to POU5F1. A putative protein of 58 amino acids was predicted and expression was detected in both normal and psoriasis skin. Sequencing of the coding region revealed a total of 11 single nucleotide polymorphisms. When comparing the frequencies of PSORS1C3 variants in a case-control material in the Swedish population, three single nucleotide polymorphisms displayed significant association with psoriasis. This association appeared to be HLA-Cw*0602-dependent due to linkage disequilibrium, thus HLA-C remains the strongest associating factor in the region.
Effect of Debio 0932 on semi-quantitative clinical psoriasis score and epidermal thickness of xenografted psoriasis skin. (A) Skin was assessed twice weekly, and given a semiquantitative clinical psoriasis score. Debio 0932 treatment significantly reduced the semiquantitative clinical psoriasis score as compared with negative control (Neg cont). From day 11 and onwards. Shown is mean ± SEM. *p < 0.001. (B) Representative clinical appearances are shown. (C) After 3 weeks of treatment, biopsies from the xenografted psoriasis skin were paraffinembedded and epidermal thickness was measured on sections stained with haematoxylin/eosin (He). Treatment with Debio 0932 significantly reduced the epidermal thickness as compared with negative control (Neg cont). Shown are each graft value and mean ± SD. (D) Representative histology of HE-stained sections are shown.
Effect of Debio 0932 on histological psoriasis parameters. After 3 weeks of treatment, biopsies from the xenografted psoriasis skin were paraffin-embedded and (A) the overall psoriasis pattern score, (B) the parakeratosis score, (C) the granulocyte score, (D) the vessel score and (E) the lymphocyte score were evaluated on sections stained with haematoxylin/eosin (He). Treatment with Debio 0932 significantly reduced the psoriasis pattern and the vessel scores compared to the negative control (Neg cont). Individual graft values and means ± SD are shown.  
Debio 0932 is a novel oral heat shock protein 90 (Hsp90) inhibitor developed for anti-cancer therapy. Surprising-ly, during the first clinical trial, one psoriasis patient experienced complete remission of his skin manifestation. However, a possible therapeutic utility of Hsp90 in psoriasis has not previously been reported. The objective of the present study was to explore the ability of Debio 0932 to alleviate psoriasis in a preclinical model. A psoriasis xenograft transplantation model was employed where skin from 5 psoriasis patients was transplanted onto immunodeficient mice (8 xenografts per donor). Debio 0932 was administered perorally daily for 3 weeks and resulted in significant clinical alleviation of psoriasis by day 11 and reduced epidermal thickness evaluated post-treatment. Alleviation of psoriasis in the psoriasis xenograft transplantation model, which may be due to Hsp90's involvement in signalling pathways that are up-regulated in psoriasis, substantiates a potential role of Debio 0932 in psoriasis treatment.
A raised baseline serum tryptase is a risk indicator for anaphylactic reactions, especially in patients with hymenoptera venom allergy. Borderline elevations (> 11.4 μg/l) occur frequently and may necessitate invasive diagnostic procedures to rule out systemic mastocytosis. We retrospectively analysed 1,092 non-mastocytotic patients from our general dermatology clinic with respect to age- and gender-associated effects and investigated the impact of heterophilic antibody interference on the tryptase assay. The results were stratified by gender and five age classes. Sera with raised tryptase (n = 106) were re-tested after pre-incubation with Heterophilic Blocking Tubes (HBT®, Scantibodies Laboratory; Santee, CA, USA). A significant increase in baseline tryptase was observed with increasing age. Incubation with HBT® caused a decline of more than 50% in only one case. In conclusion, older patients showed significantly higher serum tryptase levels and heterophilic interference was of subordinate relevance.
Top-cited authors
Howard I Maibach
  • University of California, San Francisco
Hans Christian Wulf
  • Bispebjerg Hospital, Copenhagen University
Sonja Ständer
  • Universitätsklinikum Münster
Jacek C Szepietowski
  • Wroclaw Medical University
Joanna Wallengren
  • Lund University