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The chemiluminescence arising from the reaction of bis(2,4,6-trichlorophenyl)oxalate with hydrogen peroxide in the presence of dithranol has been studied. The influence of concentration of peroxyoxalate, hydrogen peroxide, dithranol, catalyst and temperature on the resulting chemiluminescence was investigated. The kinetic parameters for the peroxyoxalate- chemiluminescence of dithranol were evaluated from computer fitting of the resulting intensity-time plots. The activation parameters Ea, ΔH‡, ΔS‡ and ΔG‡ were evaluated from temperature dependence of the fall rate constants. The chemiluminescence intensity is proportional to the concentration of dithranol. Based on these findings, a simple and rapid flow-injection chemiluminescence method has been developed for the determination of dithranol, which has been satisfactory applied in different pharmaceutical preparations. [ABSTRACT FROM AUTHOR]

Abstract: A special class of porous silica materials, silica aerogels, was recently shown to be a potential candidate for oral drug delivery systems. It was demonstrated, that stability of drugs and their dissolution rate can essentially be improved through the adsorption on to these materials. In this work, drug loaded silica aerogels are firstly applied as dermal drug delivery systems. Dithranol is used as a representative drug since there is a need to enhance its dermal availability. The unstable and nearly water-insoluble drug exhibits a poor penetration. Release of dithranol from aerogels into various semi-solid formulations and its dissolution as well as the release and penetration into artificial membranes were investigated by Fourier-transform infrared attenuated total reflection (FTIR-ATR) spectroscopy. Two model membranes (one hydrophilic and one lipophilic) were applied. Several formulations were tested and the most promising one was used in order to study the penetration of dithranol into human stratum corneum (SC). Dithranol adsorbed on hydrophilic silica aerogels exhibited superior penetration behaviour compared to that of the standard ointment (dithranol in white soft paraffin). [Copyright &y& Elsevier]

Background Calcipotriol ointment and short-contact dithranol cream therapy are well-established topical treatments for psoriasis. Quality of life, i.e. the physical, psychological, and social functioning and well-being of the patient, has become an essential outcome measure in chronic skin disease. Objectives To compare the quality-of-life outcomes of calcipotriol ointment with that of short-contact dithranol cream in a supervised treatment regimen, and to determine the degree of improvement in quality of life these topical treatments can accomplish. Methods In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily in a 12-week intensive treatment programme. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Quality of life was assessed with the Skindex-29 and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36). Results At the end of treatment, no statistically significant differences were found between the calcipotriol and the dithranol group in any of the quality-of-life domains or scales of the Skindex-29 and the SF-36. Over time, a significant improvement of quality of life was found on all three scales of the dermatology-specific Skindex-29, predominantly of a moderate magnitude. In the calcipotriol group, a significant change of a small magnitude was found in the Physical Component Summary of the SF-36. No significant changes were found in the Mental Component Summary (or on any of the eight scales composing the questionnaire) of the SF-36. Conclusions The hypothesis was confirmed, that no statistically significant differences in improvement of quality of life could be found between calcipotriol ointment and dithranol short-contact cream in a day-care setting. Given this result, both calcipotriol and dithranol can be welcome alternatives for the patient. Calcipotriol, being more practical and patient friendly, can be considered as a first-line approach in clinical practice. However, in patients recalcitrant to calcipotriol and/or other topical treatments, preference should be given to the dithranol regimen. Topical treatment in combination with interventions explicitly focusing on improvement of coping behaviour and psychosocial functioning may further increase the degree of improvement in the psychosocial domains of quality of life. The results of this study are likely to give further evidence to the notion that the generic SF-36 is little or not responsive to small to moderate changes in quality of life in mild to moderate psoriasis. [ABSTRACT FROM AUTHOR]

Abstract: The cutaneous and mucosal surfaces in the infraorbital region around the whisker pad are innervated by the maxillary division of the afferent fibers of the trigeminal nerve, while certain ganglion cells project to the principal sensory trigeminal nucleus (Pr5). In turn, some of the neurons in the Pr5 project to the motor trigeminal nucleus (Mo5), whose neurons do not innervate the infraorbital skin. We analyzed the calmodulin (CaM) gene expression in these nuclei after dithranol-induced inflammation and subsequent treatment with corticosteroid in the infraorbital skin. CaM gene-specific mRNA populations were detected through quantitative image analysis of the distribution of CaM gene-specific riboprobes in brain stem cryostat sections of control rats and rats chronically treated with dithranol, corticosteroid or both. These nuclei displayed a differentially altered CaM gene expression in response to the treatments. While the CaM I and II mRNA contents were increased, the CaM III transcripts remained unaltered after chronic dithranol treatment in the Mo5. In the Pr5, however, the CaM mRNA contents were either unchanged (CaM I and III) or increased (CaM II). Subsequent corticosteroid treatment reversed the stimulatory effects of dithranol on the expression of all the CaM genes in the Mo5, but was without significant effects on the CaM I and II genes, or even increased the CaM III mRNA contents in the Pr5. Corticosteroid treatment alone was either ineffective or decreased the levels of CaM mRNAs in these nuclei. These data suggest that peripheral noxae of dermal origin may result in a trans-synaptically acting differential regulation of the multiple CaM genes in the brain. [Copyright &y& Elsevier]

Dithranol is infrequently used in psoriasis in spite of excellent efficacy due to its local adverse effects. We have synthesized a novel formulation of dithranol in which the drug is entrapped in phospholipid liposomes. This formulation has shown markedly low irritation and minimal staining of skin and clothes in preliminary studies. Twenty patients with bilaterally symmetrical stable plaque psoriasis applied 0.5% dithranol lipogel to lesions over one side of the body. On the other side, 10 patients were randomized to apply pure liposomal base and 10 applied a conventional cream containing 1.15% dithranol, 1.15% salicylic acid and 5.3% coal tar in a 30-minute, short contact regimen for 6 weeks. Patients were assessed for disease severity, perilesional erythema and skin staining, pruritus and any other adverse effects at baseline, 2, 4 and 6 weeks. Both lipogel and the cream significantly reduced the total severity score compared to the liposomal base at 4 (p = 0.004) and 6 (p = 0.01) weeks. There was no significant difference in the clinical response of dithranol cream and lipogel. Markedly low incidence and severity of perilesional erythema (p<0.001) and skin staining (p<0.05) was seen with the lipogel in comparison with the cream. [ABSTRACT FROM AUTHOR]

Abstract: Dithranol has been used to treat psoriasis for decades. Although its beneficial effect may involve the induction of cutaneous inflammation, and inflammation often leads to damages in nerve fibers, these alterations are not well documented. Therefore, we investigated the effects of dithranol on the immunohistochemical characteristics of the cutaneous nerve fibers in the rat skin. Epidermal nerve fiber staining was achieved with ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) immunohistochemistry in the orofacial skin of control rats, rats treated with (a) dithranol for 5 days, (b) corticosteroid for 5 days following dithranol treatment for 5 days, and (c) corticosteroid for 5 days. The results revealed a complete loss of UCH-L1 immunoreactivity in the dithranol-treated animals. Topical application of corticosteroid onto the inflamed skin for 5 days reversed this effect: the UCH-L1 immunoreactivity was almost completely restored. Steroid treatment for 5 days did not change the appearance of the UCH-L1-immunoreactive nerve fibers. These findings were supported by Western blot analyses. We conclude that dithranol, incidentally similarly to psoriasis, causes inflammation and abolishes UCH-L1 immunoreactivity in the rat orofacial skin in a corticosteroid-reversible manner. This phenomenon may be due to the ability of dithranol to cause oxidative damage to the UCH-L1 protein, and to the antioxidant activity of the corticosteroids countering this effect. [Copyright &y& Elsevier]

Background Calcipotriol has become a first-line treatment for psoriasis. Its efficacy and safety have been shown in many comparative clinical trials carried out in outpatients. In a comparative study in patients visiting the outpatient department once every 14 days, it was shown that calcipotriol was more effective and better tolerated compared with dithranol. Objectives To compare the clinical efficacy of calcipotriol ointment with that of dithranol cream in a supervised treatment regimen. Methods In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Results This study failed to prove that calcipotriol is as efficacious as dithranol when used in a day-care setting (noninferiority test). The mean percentage reduction in Psoriasis Area and Severity Index from baseline to end of treatment was 57·0% in the calcipotriol group vs. 63·6% in the dithranol group. However, the two-sided test for superiority indicated no statistically significant difference between the treatment groups ( P = 0·39). At the end of treatment, 15% of the patients treated with calcipotriol ointment and 25% of those treated with dithranol cream did not require any further treatment. Although calcipotriol ointment appeared to be more effective during the first 8 weeks, a difference was no longer apparent at 12 weeks. In comparison with the high number of drop-outs due to cutaneous side-effects in the calcipotriol group, the frequency of a tolerable degree of irritation appeared to be higher in patients treated with dithranol. However, concomitant corticosteroid treatment of dithranol irritation in seven patients may have contributed to this difference between both treatments. Moreover, patients receiving therapy with calcipotriol ointment experienced fewer application-related skin and subcutaneous tissue disorders than patients treated with dithranol cream: 21 of 53 (40%) and 37 of 52 (71%), respectively. This difference is statistically significant ( P = 0·001). Conclusions The hypothesis that calcipotriol ointment might be at least as effective as dithranol cream in the day-care setting could not be proven in the present study. Whereas calcipotriol has become a mainstay in the routine outpatient treatment of psoriasis not requiring a day-care setting, dithranol treatment, being difficult as a routine outpatient therapy, has increased efficacy and improved tolerability if the treatment is carried out in a day-care setting. [ABSTRACT FROM AUTHOR]

Keratinocyte growth factor receptor (KGFR = FGFR2-IIIb) is a tyrosine kinase receptor expressed by keratinocytes, which mediates the effects of fibroblast growth factors (FGF). There are contradictory data in the literature regarding the role of FGFR2-IIIb during the proliferation/differentiation programme of keratinocytes. In this study, we aimed to investigate whether overexpression of FGFR2-IIIb may have a role in the regulation of keratinocyte proliferation. We analysed the expression of FGFR2-IIIb in an in vitro HaCaT model system representing different stages of proliferation and differentiation of keratinocytes. Real-time RT-PCR and Western blot analyses demonstrated a correlation between FGFR2-IIIb mRNA and protein expression and the proportion of cells in S/G2/M phase in synchronized HaCaT keratinocytes and thus with proliferation activity ( r = 0.96). After treatment with the antipsoriatic drug, dithranol, FGFR2-IIIb is downregulated dose dependently both at mRNA and protein levels. Moreover, when the rate of proliferation is decreased by the lack of cell attachment to the culturing surface, FGFR2-IIIb mRNA ( P = 0.0315) and protein expressions were also reduced ( P = 0.0242), while a differentiation marker, keratin 10, mRNA ( P = 0.0003) and protein levels ( P = 0.001) were increased ( r = −0.92). Based on our results we conclude that FGFR2-IIIb expression in HaCaT keratinocytes corresponds with the proliferative activation of the cells and is not related to the differentiation programme. [ABSTRACT FROM AUTHOR]

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Background: Although topical azelaic acid has been previously used for the treatment of alopecia, no controlled trials of azelaic acid for this condition have been conducted to date. Objective: The goal of this study was to determine the efficacy, tolerability, and safety of azelaic acid treatment in patients with patchy alopecia areata (AA) in comparison with anthralin (dithranol) treatment. Subjects and methods: This study included 31 subjects with patchy AA who did not receive any treatment for at least 1 month prior to the study. Demographic and clinical characteristics of these subjects were recorded at baseline. Subjects were randomized to apply either 20% azelaic acid (15 subjects) or 0.5% anthralin (16 subjects) for 12 consecutive weeks. In a subsequent 8-week follow-up period no cream was applied. Two independent investigators performed an efficacy evaluation with clinical examination using a terminal hair regrowth score (RGS) with a scale ranging from 0 (inadequate response) to 2 (complete response) at week 20. Partial response was accepted as score 1. Results: Both groups were well matched for the relevant demographic and clinical indicators affecting treatment response at baseline. All subjects completed the trial. At week 20 the RGS was 1.27 ± 0.9 in the azelaic acid group versus 1.37 ± 0.8 in the anthralin group (p > 0.05). A complete response was observed in 53.3% of cases in the azelaic acid group (8 of 15) compared with 56.2% (9 of 16) in the anthralin group (p > 0.05). No serious adverse events were observed in either group during the study. Conclusion: The present pilot study showed that the use of azelaic acid gave similar results to anthralin with regard to hair regrowth, and that it can be an effective topical therapy for patchy AA. More extensive trials are necessary, however, to reach a definitive conclusion. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, inflammatory, hyperproliferative skin disease that affects 1–2% of the general population in the UK and US. Plaque psoriasis is the most common form, accounting for approximately 90% of cases. The disease is usually chronic and persistent, although up to 50% of patients may enter spontaneous remission for varying periods of time. There is no cure for psoriasis; therefore, the aim of treatment is to minimize the extent and severity of the disease to the point at which it no longer substantially disrupts the patient’s quality of life. First-line therapy of psoriasis usually consists of topical agents, such as emollients, tar, dithranol, and vitamin D3 analogs. In cases of severe, extensive psoriasis, where topical therapy is either impractical or not sufficiently effective, systemic treatment may be warranted at the outset. In these circumstances, the therapeutic options include: (i) intensive inpatient or day center topical therapy; (ii) phototherapy; and/or (iii) systemic agents. There are now a number of systemic agents available for the treatment of severe psoriasis, but all have potential adverse effects. We review the current treatment options, which include the use of phototherapy and systemic agents, and provide recommendations on their use in clinical practice. Importantly, treatment should be tailored to each individual patient depending on concurrent medical problems (which might preclude certain agents), patient choice and acceptance of the risk of adverse effects. [ABSTRACT FROM AUTHOR]

Several topical treatments are available for patients with psoriasis. Although individualization of the treatment remains important, there is a need for treatment recommendations to identify the best treatment out of the available treatments and to help with improvement in treatment compliance. In this communication we give our views on the assessment of severity of psoriasis. We provide recommendations for selection of treatments, reconciling the clearance phase and the long-term management. Finally, we provide recommendations for the treatment of particular localizations: the scalp and psoriasis at sensitive sites. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The irritant response of perilesional skin is a serious limitation of dithranol therapy in psoriasis. No data are available on the actual prevalence and severity of irritation during 24-h dithranol treatment in an inpatient setting. Using a retrospective analysis of 68 patients with psoriasis visiting our inpatient department for dithranol treatment, the occurrence of dithranol irritation was studied. We found a relatively high frequency of dithranol irritation. Furthermore, most irritation occurs at the start of the therapy with relatively low concentrations. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary Background Narrow-band ultraviolet (UV) B (311 nm) phototherapy is an effective treatment for psoriasis. In order to reduce cumulative UV doses and to enhance clearance of psoriasis plaques, combination therapies with topical agents such as dithranol and calcipotriol have been established. Objectives To compare the clinical efficacy, in a half-side manner, of UVB (311 nm) in combination with either calcitriol or dithranol. Methods Ten patients with symmetrical stable plaque psoriasis were treated with narrow-band UVB (311 nm) five times a week. In addition, topical calcitriol was applied twice daily to one arm, whereas the other arm and the rest of the body were treated once daily with dithranol. The follow-up period was at least 4 weeks. Efficacy was assessed separately for both arms prior to treatment and once weekly thereafter by a modified Psoriasis Area and Severity Index (PASI) score. The cumulative irradiation dose and the number of treatment sessions required for clearance of psoriasis lesions were determined for each patient. Additionally, all patients completed a quality of life questionnaire. Results Both treatment modalities notably reduced the PASI score. A clinical comparison of UVB (311 nm) in combination with either calcitriol or dithranol revealed no significant therapeutic differences between the regimens. Conclusions Combination of narrow-band UVB (311 nm) therapy with calcitriol is equally effective as the combination with dithranol for the treatment of psoriasis. However, patients preferred calcitriol rather than dithranol when both quality of life and treatment acceptability were assessed. [ABSTRACT FROM AUTHOR]

Current information on the incidence of patch-test positivity and the spectrum of allergens in psoriatics is conflicting. We compared the rates of patch-test positivity to common allergens and topical medicaments in 200 patients suffering from chronic plaque psoriasis (group I) with 51 patients with other non-allergic skin complaints (group II) and 54 patients suspected of having allergic contact dermatitis (group III). Positive patch-test results to one or more allergens were detected in 21.6 % of patients in i [sup group I, 23.5 % n group II and 50.0 % in group III.] Psoriatics with [sup ≥] 5 years old disease had a higher rate of patch-test positivity than those with shorter disease duration (p<0.01). The site of lesions showed no correlation with patch-test positivity. The commonest allergens showing positivity in group I were dithranol (6.5%), nickel (6%), fragrance mix (5%), neomycin (2%) and nitrofurazone (2%). In spite of the comparable rates of patch-test positivity in psoriatics and general dermatology outpatients, the predominance of sensitivity to topical medicaments and fragrance in the former group was striking. A separate psoriasis series focusing on topical agents may give more accurate information on this subject. [ABSTRACT FROM AUTHOR]

AIM: To test the staining potential of a novel liposomal dithranol gel on different types of fabrics and compare it with the only commercially available dithranol preparation in India, Derobin™. METHODS: Pure cotton, pure polyester and four blends of the two fabrics were tested for staining and washability. RESULTS: Both products showed the least staining and spreading on pure cotton with progressively worse stains as the proportion of polyester in the fabric increased. When compared with each other the liposomal dithranol gel showed markedly lighter staining than Derobin on all fabrics. It also washed off completely with water whereas the Derobin stains could not be washed off, even with detergent. CONCLUSION: The liposomal gel due to its superior staining properties may potentially increase the acceptability of dithranol amongst psoriasis patients. [ABSTRACT FROM AUTHOR]

Summary Background This study was part of a large national cost-effectiveness analysis, and was funded by the National Fund for Investigational Medicine of the Health Care Insurance Board. Objectives To compare the costs of treatment of moderate to severe psoriasis by dithranol short contact therapy in a care instruction programme (short contact therapy) with ultraviolet B phototherapy (UVB) and inpatient dithranol treatment (inpatient treatment), and relate these costs to treatment effectiveness. Methods An open randomized controlled multicentre study was performed. The costs (both medical and non-medical) were calculated for the following periods: during treatment, per month during remission, after a relapse, and following an unsuccessful treatment. The effectiveness measures were the clinical response rate and the number of clearance days during follow-up. Results The data from 216 patients were analysed. The mean overall costs per patient during treatment were €1641, €1258 and €7706 for short contact treatment, UVB and inpatient treatment, respectively. During the clearance period the mean costs per month per patient were €19, €5 and €25, respectively. The clinical response rates were 57%, 57% and 85%, respectively. The mean number of clearance-days after short contact treatment was 160 [median 119; interquartile range (0–357)], which was not significantly different from the other two strategies: 211 clearance-days after inpatienttreatment [241 (99–350)] and 136 clearance-days after UVB [81 (0–266)]. Conclusion Short contact treatment is an attractive alternative for patients with moderate to severe psoriasis currently treated by inpatient treatment, as the costs of short contact treatment were significantly lower and the number of clearance days was comparable. Considering the higher costs, short contact treatment is not a first choice treatment when compared with UVB. [ABSTRACT FROM AUTHOR]

Summary Background It is well known from clinical practice that repeated treatment with dithranol leads to the development of tolerance. Objectives To investigate the characteristics and mechanism of such dithranol tolerance. Methods The mouse ear was pretreated with a low dose of dithranol or croton oil or, in previously sensitized animals, with dinitrofluorobenzene (DNFB). Twenty-four hours later irritant dermatitis was elicited by painting the mouse ear with a high dose of dithranol, croton oil or DNFB, and the dermatitis was characterized by measurement of ear thickness. Results Low-dose dithranol significantly suppressed dithranol-induced oedema, whereas it had no effect on croton oil- or DNFB-induced dermatitis, suggesting that dithranol-induced tolerance is specific. Tolerance to dithranol could not be induced by pretreatment of the mouse ear with a low dose of croton oil or DNFB. Mild tape stripping of the mouse ear also inhibited the inflammatory effect of dithranol applied 24 h later. Superoxide dismutase treatment abolished the tolerance-inducing effect of low-dose dithranol or stripping. Conclusions These results suggest that superoxide anion radicals are involved not only in the inflammatory effect of dithranol, but also in the induction of tolerance. [ABSTRACT FROM AUTHOR]

Summary Background Since its introduction, the effectiveness of dithranol in treating psoriasis has been unequalled by other topical treatments. Out-patient short-contact dithranol treatment is effective with regard to clinical response rate and relapse rate after 1 year. A drawback, however, is the relatively long treatment duration. Objectives To study a dithranol regimen combined with a potent topical corticosteroid with regard to clinical response rate, treatment duration and remission period after clearance. Methods Twelve patients with stable psoriasis vulgaris participated in this study. We treated three comparable psoriasis lesions on the extremities for 39 consecutive days. The first lesion was treated daily with short-contact dithranol cream followed by clobetasol-17-propionate ointment 5 days per week. The second lesion was treated daily with short-contact dithranol cream followed by the vehicle of clobetasol-17-propionate ointment. The third lesion was treated with clobetasol-17-propionate ointment 5 days per week. The patients attended on days 1, 4, 9, 12, 15, 18, 22, 25, 32 and 39 during treatment. We assessed lesional severity scores at each visit and registered the baseline area at the first visit. During the follow up at weeks 2, 4, 6, 10, 14, 19 and 23 we assessed lesional sum scores. We also estimated the area involved in recurrence of the lesion as a percentage of the baseline area. The overall differences between the three treatment curves for the treatment period and follow-up period separately were tested with a likelihood ratio test. Results Differences between the curves of the sum scores during treatment (P < 0·001) were mainly due to the different time-course of dithranol monotherapy, which showed a slower decrease in sum score. Differences between the linear trends of the sum score (P < 0·001) and the area score (P < 0·001) during follow up were due to a different time-course of the combination therapy, which started... [ABSTRACT FROM AUTHOR]

Background Non-invasive bioengineering methods are widely used in the assessment of irritant skin reactions. Objectives To assess the ability of eight non-invasive measurement techniques to distinguish changes in skin conditions over time, these changes being induced by five different irritants. Methods The following techniques were compared in a multivariate analysis: laser‐Doppler perfusion imaging (LDI), laser‐Doppler flowmetry (LDF), transepidermal water loss (TEWL), visual scoring (VS), colorimetric measurements (Chromameter CR 200 a* and L* scales), Mexameter Hb scale (Mexa Hb) and capacitance (Corneometer CM 820). Irritants tested were sodium lauryl sulphate 2% (SLS), tape stripping (TS), tretinoin 0·05% (TRET), ultraviolet (UV) exposure to 30 W m-2 UVB/95 W m-2 UVA, and dithranol 0·5% (DIT). Measurements were performed at baseline and after 24, 48 and 72 h. The study was conducted on the upper back of 11 healthy volunteers of both sexes aged 27–51 years. Results For DIT it was possible to discriminate over time with CR 200 a* and L*, VS, LDI, LDF and Mexa Hb. In SLS discrimination over time was seen with TEWL and LDF. Discrimination in TS was demonstrated for TEWL, VS, CR 200 a*, CM 820, LDF, LDI and Mexa Hb. In TRET discrimination ability was seen for LDI, LDF, Mexa Hb and VS. For UV it was possible to discriminate using VS, TEWL, LDF, LDI and Mexa Hb. Conclusions Different irritation patterns need different measurement modalities in order to give optimal discrimination over time. [ABSTRACT FROM AUTHOR]

Background Dithranol (anthralin) has been known to be effective in the treatment of psoriasis for more than 80 years. However, perilesional and uninvolved skin often show irritation during dithranol treatment, which limits its use. As the relapse rate of psoriasis is worsened by adding corticosteroids to a dithranol regimen, the use of topical corticosteroids to reduce dithranol irritation is controversial. Objectives The aim of the present study was to investigate the clinical and cell biological effect of clobetasol-17-propionate 0·05% ointment on dithranol-treated lesional and perilesional skin. Methods For 17 consecutive days, 2% dithranol cream was applied on two test sites. A third site was left untreated on all participating patients (n = 8). All sites consisted of a psoriasis lesion as well as a 3-cm zone of perilesional skin localized on the back. After 1 h, the cream was washed off, and subsequently one of the dithranol-treated sites was treated once a day with clobetasol-17-propionate 0·05% ointment. The second site was treated once daily with the vehicle. On day 17, punch biopsies were taken from all three lesions and from the perilesional zone of all test sites in order to perform an immunohistochemical investigation, using markers to assess proliferation, differentiation and inflammation. Results The SUM score (erythema + induration + scaling) of the lesion treated with dithranol/clobetasol showed a pronounced reduction, which was significantly greater than the SUM score of the lesion treated with dithranol/vehicle. However, the scores of both sites were equal by 6 weeks of follow-up. Comparing the two treated lesions, we observed a lower number of cycling epidermal cells in the dithranol/clobetasol lesion and a significantly lower perivascular dermal score of T lymphocytes. Comparing the perilesional skin of the two treated sites we observed less cycling epidermal cells in the dithranol/clobetasol-treated site. Regarding perilesional differentiation, the interpapillary involucrin expression was higher in the dithranol/clobetasol-treated site. With respect to perilesional inflammation the expression of dermal polymorphonuclear leucocytes, monocytes, macrophages and T lymphocytes in the dermal infiltrate were significantly lower in the dithranol/clobetasol-treated site. Conclusions The addition of clobetasol-17-propionate enhanced the antipsoriatic efficacy of dithranol by interfering with T-cell accumulation and epidermal proliferation. The addition of a corticosteroid reduced perilesional dithranol inflammation at the cellular level, although clinically detectable dithranol erythema was not reduced. [ABSTRACT FROM AUTHOR]

The use of vitamin D analogues for the treatment of chronic plaque psoriasis is well documented. Of importance now is their comparability and compatibility with other established treatments for psoriasis. This paper reviews five studies with calcitriol 3 μg g-1 ointment (Silkis ointment®, Galderma Laboratories). Calcitriol applied twice daily was found to be as effective as short-contact dithranol in terms of global improvement and PASI scores. However, patients favoured calcitriol over dithranol when both quality of life and treatment acceptability were assessed. Two studies provide evidence of the benefit of combining calcitriol with other antipsoriatic therapies. Combination with ultraviolet (UV) B phototherapy proved as effective as UVB alone over an 8-week period; however, the combination had a radiation dose-sparing effect, thus reducing the risk of adverse events. Likewise, calcitriol combined with betamethasone valerate (each applied separately, once daily) was as efficacious as twice-daily betamethasone, thereby achieving a corticosteroid-sparing effect. Finally, two studies confirm that calcitriol 3 μg g-1 ointment can be used safely in patients with psoriasis of the head and confirm the high level of clinical efficacy achieved with this compound. [ABSTRACT FROM AUTHOR]

Epidermal growth factor (EGF) is a mitogen dial stimulates cell division of various cells of epidermal origin. The present study was undertaken to clarify whether the serum level of EGF is correlated with the disease activity during local therapy with dithranol in psoriasis. We examined serum EGF concentrations in acute and chronic psoriasis before and after topical treatment with dithranol and the correlation with Psoriasis Activity and Seventy Index PASH. Male patients were divided into two groups: acute psoriasis (AP. 17 cases) and chronic psoriasis (CP. 17 cases). A control group C consisted of 20 healthy male volunteers. Radioimmunoassay of EGF was performed using the reagent pack (Amersham. UK). In the CP group mean EGF was higher before treatment ban in the AP and C groups, but not significantly. EGF concentration after local treatment was higher in the CP group than the AP group (P < 0.02) the AP group, however, showed statistically significant decrease of EGF after the treatment (P < 0.04). No correlation between EGF and PASI was found. Serum EGF concentration increased in 19/35 treated patients. Kevnvrds: Serum epidermal growth factor: Psoriasis: Male: Dithranol [ABSTRACT FROM AUTHOR]

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Dithranol (D) is used as a therapeutic topical agent to treat psoriasis, although it produces inflammation and staining of skin and clothing. D-induced irritation has been evaluated by visual scoring and by bioengineering techniques. evidencing modifications of the inflammatory parameters, but no alterations of the skin barrier. The aim of our study was to evaluate the irritant reactions induced by D using ultrasound, and to compare the B-scanning data with visual assessments and colorimetric measurements. 13 healthy women underwent 2, 3-h patch tests with, respectively, 0.02% and 0.1% D in white petrolatum and 1 24-h patch test with 2% sodium lauryl sulfate (SLS). For assessing skin reactions, clinical judgement, colorimetry and echography were employed. Echographic images were evaluated by skin thickness measurements and segmentation procedures, using an 0-30 interval, marking the hyporeflecting areas in the dermis, and a 201-255 interval, assessing the hyperreflecting components of the image (both epidermal and dermal). In all subjects. D produced uniform reactions, the intensity varying according to concentration. Both echographic parameters of inflammation (skin thickness and 0-30 areas) showed an increase at all times of assessment. The 201-255D/0-30 pixel ratio, describing the distribution of dermal edema, indicated that strong inflammatory reactions, such as those caused by the application of 0.1% D, are accompanied by edema in the lower portion of the dermis. Finally, in contrast to SLS reactions, where a 24-h reduction in epidermal reflectivity was observable, D reactions appeared with an accentuation of the 201-255 epidermal hand at 24-96-h examinations. [ABSTRACT FROM AUTHOR]

The contact sensitizing activity of dithranol and butantrone (10-butyryl dithranol) was studied in 3 animal models: the guinea pig maximization test (GPMT), the closed patch test (CPT), and the ear swelling test (MEST) in 2 different mouse strains. In the GPMT, both dithranol and , to a greater extent, butantrone showed sensitizing potential. Because butantrone was less irritant, the concentrations used were 10 × higher than those of dithranol. In the CPT, only butantrone was slightly positive. In the MEST, with both CF-I and Balb.c mice, dithranol caused less swelling of the test ear after challenge than butantrone. According to the evaluation criteria of the MEST, only butantrone caused sensitization in 50% of the CF-I mice and in 40% of the Balb.c mice. Thus, the GPMT was the only test which indicated the minor contact sensitizing potential of dithranol. On the other hand, the 10-butyryl analogue of dithranol showed undoubtedly stronger contact sensitizing potential than the parent compound in all tests. Therefore, as compared to dithranol, an increased risk of sensitization should be considered. [ABSTRACT FROM AUTHOR]

Continuous topical administration of dithranol and butantrone for 6 months caused different irritation profiles in miniature swine. In paraffine wax sticks in white petrolatum, butantrone gave rise to much less initial irritation than dithranol, but after 2-3 weeks the situation had equalized. In gel formulations, butantrone was initially more irritant than dithranol. The vehicles themselves induced significant irritation. Signs of skin hyperplasia (parakeratosis and acanthosis) and inflammation were frequent histopathological findings at the end of the study, but no malignant changes ere found. Dithranol and butantrone did not produce any chemical, hematological or serious histological abnormalities during the treatment, suggesting a lack of systemic toxicity. No evidence of systemic absorption was found. This long-term study did not predict delayed irritation of butantrone observed in about ⅓ of the psoriatic patients after treatment for 1-2 months. [ABSTRACT FROM AUTHOR]

The distribution of immunocompetent cells was analyzed in allergic (nickel) and irritant (dithranol) patch tests using conventional transmission electron microscopy and labeling with monoclonal antibodies in an avidin-biotin immunoperoxidase study. The biopsies were taken 24 or 48 h after the allergen/irritant application. In allergic and irritant reactions, most inflammatory cells were OKT11 positive (pan T lymphocytes). The majority of these cells were also OKT4 positive (helper/inducer T lymphocytes), while the minority were OKT8 positive (suppressor/cytotoxic T lymphocytes). NK9 positive cells (natural killer cells) were observed in small numbers. The number of dendritic OKT6 and OKlal positive cells (Langerhans cells) in the epidermis was unaffected in allergic reactions. In irritant reactions, a normal number of OKT6 positive Langerhans cells was observed, while the number of OKlal positive cells had increased in the epidermis. Dithranol caused prominent line structural changes in the mitochondria of the Langerhans cells, while the keratinocytes appeared largely unaffected. The present study indicates that allergic and irritant patch tests cannot be differentiated reliably using current immunohistopathological or electron microscopic techniques, in spite of the small differences observed. [ABSTRACT FROM AUTHOR]

During treatment with a dithranol-containing collodion for common warts, a patient developed a eczematous reaction on the treated sites and the extremities. Patch testing revealed a contact allergy to dithranol. Two applications of the collodion cured the warts within 3 weeks. It is argued that contact allergy to dithranol occurs more frequently than is suspected. [ABSTRACT FROM AUTHOR]

The effects of dithranol and its therapeutically inactive oxidation product, danthrone, on 12(S)-HETE binding to the human epidermal cell line SCL-II were studied. Dithranol (0.25-1 Μg/ml), in contrast to danthrone, induced a substantial decrease in 12(S)-HETE binding in a dose-dependent manner. The inhibition occurred after a latency period of 6 h, reached its maximum at 18-24 h and slowly declined thereafter. At a concentration of 1 Μg/ ml, the drug led to an approximately 50% decrease in the number of specific high-affinity 12(S)-HEFE receptors (B), whereas receptor affinity (K) showed no change. The down-regulation of 12(S)-HETE receptors on epidermal cells by dithranol may contribute to its antipsoriatic action. [ABSTRACT FROM AUTHOR]

Dithranol-induced skin irritation and the modulatory effects of different pharmacological agents were studied using the mouse ear model. A single topical application of dithranol caused a dose-dependent skin irritation which resulted in delayed swelling of the mouse ear with two separate peak responses, 1-2 and 6-10 days after application. The irritation was most effectively and persistently inhibited by topical treatment with corticosteroids, the free radical scavenger DL-α-tocopherol (DLAT) and the serotonin antagonist metergoline. The effect of corticosteroids, however, was slightly diminished during the second peak irritation. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), the dual lipoxygenase and cyclo-oxygenase inhibitor tolfenamic acid and the cyclo-oxygenase inhibitor indomethacin as well as trifluoperazine retained their inhibitory activity. Of these compounds, indomethacin was active only during the first irritation peak, NDGA during both peaks and trifluoperazine principally during the second peak. Retinoic acid did not inhibit the ear swelling. The results confirm and extend the observations that the formation of free radicals is essential for dithranol inflammation. The inflammation can also be suppressed by inhibiting the formation of arachidonic acid or its pro-inflammatory metabolites. [ABSTRACT FROM AUTHOR]

HaCaT cells, a rapidly multiplying human keratinocyte line, were tested for their sensitivity to antipsoriatic dithranol with regard to classical proliferation parameters and for the drug's action on the plasma membrane integrity by the dose- and time-dependent release of cytosolic lactate dehydrogenase (LDH). In the case of H thymidine as well as C amino acid incorporation the 50% inhibition concentration (IC) was 0.2 Μ M dithranol 24 h after initial exposure to the drug. For protein content of attached cells the IC proved to be>3.0 Μ M. Using 0.3, 1.0 and 3.0 Μ M dithranol, significant ( p<0.05) dose dependent LDH release of 0.866±0.387, 1.842±1.127 and 2.938±1.635 mU per hour and cm confluent culture area was measured between the 5th and the 24th hour, compared to an acetone control of 0.504±0.299 mU/ h×cm. Between the 2nd and the 4th hour as well as from the 25th to the 48th hour and the 49th to the 72nd hour the LDH release after dithranol treatment did not exceed the control value. In accordance with these findings dose-dependent morphological signs of cell injury were detected by phase contrast microscopy beyond the 4th hour. The data reveal that: HaCaT cells are a very sensitive target for the antiproliferative action of dithranol; the drug causes considerable plasma membrane damage even at concentrations as low as 0.3 Μ M; and this membrane damage becomes evident after a latency of at least 4 h and for a limited period of up to 24 h. [ABSTRACT FROM AUTHOR]

The effects of different pharmacological substances on dithranol-induced irritative dermatitis were studied in mice. Pretreatment of the animals with a specific platelet activating factor (PAF) antagonist, BN 52021, significantly reduced the ear swelling in a dose-dependent manner. The cyclooxygenase inhibitor indomethacin, the antihistamine clemastine, and the antioxidant superoxide dismutase also proved to be effective in the reduction of the dermatitis. The results provide evidence of the coinvolvement of PAF, prostaglandins, histamine, and reactive oxygen radicals in dithranol-induced irritative dermatitis in mice. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The oral LD values of an antipsoriatic drug, dithranol, were 1542 mg/kg in NMRI mice and 3216 mg/ kg in Wistar rats. Three 10-acyl analogues of dithranol (10-acetyl, 10-propionyl and 10-butyryl dithranol or butantrone) were more toxic both in mice and rats. They were mutagenic only in TA1537 of the five Salmonella typhimurium strains tested. None of them were mutagenic in two Escherichia coli strains. Butantrone was least toxic to test bacteria and had the lowest mutagenic activity on TA1537. In metaphase analysis of in vitro treated human lymphocytes, dithranol, 10-acetyl dithranol and 10-propionyl dithranol produced significant increases in the number of chromosome and chromatid gaps but without a clear dose-response relationship, and without inducing significant breaks. Butantrone did not cause significant increases in gaps or breaks. In the mouse micronucleus test, dithranol and butantrone caused no increases in micronucleated polychromatic or normochromatic erythrocytes, indicating lack of clastogenic activity in vivo at maximum tolerated doses. Hence, dithranol and its 10-acyl analogues have a weak mutagenic activity in vitro. The mutagenic activity of butantrone is lower than that of the other analogues and dithranol. [ABSTRACT FROM AUTHOR]

In an in vitro model, the release and penetration through a silicon membrane of different cream formulations and ointments containing 0.5% dithranol were studied. The results indicated that the method is not suitable for predicting in vivo release and penetration. Experiments with rabbits showed that the degree of skin irritation produced by a hospital-prepared product containing 0.5% dithranol was comparable to that of a commercial product. Clinical efficacy and side-effects of these two products were investigated in a double-blind left-right comparative study in 35 patients with chronic plaque psoriasis. The two creams proved to be equally effective and showed the same incidence of side-effects. [ABSTRACT FROM AUTHOR]