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P C M Van De Kerkhof - One of the best experts on this subject based on the ideXlab platform.

  • Transepidermal water vapour loss is not increased during and following Dithranol irritation.
    British Journal of Dermatology, 2010
    Co-Authors: E. Snater, P.g.m. Van Der Valk, E.a.a.j. Janssen, P C M Van De Kerkhof
    Abstract:

    Dithranol is established as a very successful treatment for psoriasis. Its main disadvantages are irritation and staining at sites of application. The aim of the present study was to elucidate further the mechanism of Dithranol-induced irritation, in particular to what extent this is related to an impairment of the skin barrier. Dithranol 3% in cream, paste and petrolatum was applied to the forearm skin of 20 volunteers and left in situ for 1 h. Transepidermal water loss (TEWL) was measured during a period of 2 weeks following Dithranol application. In addition, a visual scoring system and colorimetry were used to assess erythema. The study showed conclusively that TEWL was not affected by the application of Dithranol, even though pronounced erythema occurred.

  • Dithranol therapy in childhood psoriasis: unjustifiably on the verge of falling into oblivion.
    Dermatology, 2010
    Co-Authors: M.e.a. De Jager, E M G J De Jong, P C M Van De Kerkhof, Marieke M.b. Seyger
    Abstract:

    Background: In childhood psoriasis, physicians aim for an effective and safe treatment such as with Dithranol. This study presents the largest study of Dithranol-treated patients described in the literature. Objective: The aim of the study was to determine the position of Dithranol in the treatment strategy for psoriasis. Methods: All juvenile patients receiving Dithranol treatment at our center were evaluated retrospectively. Results: Sixty patients (with 82 treatment episodes in total) were included. The mean age at the start of Dithranol treatment was 11.1 years (range: 3.7–17.9 years). The result of the treatment was: excellent (3.7%), good (69.5%), moderate (8.5%), reasonable (13.4%) or disappointing (4.9%). Mild irritation was seen in 39%, and severe irritation in 63% of the patients. Conclusions: Dithranol can be regarded as an efficacious and safe topical therapy for the treatment of childhood psoriasis. It is a valuable alternative topical treatment which should not be disregarded in the treatment regimen for childhood psoriasis and should be commenced before ultraviolet or systemic treatments are initiated.

  • The Relevance of Salicylic Acid in the Treatment of Plaque Psoriasis with Dithranol Creams
    Skin Pharmacology and Physiology, 2009
    Co-Authors: S. De Mare, N. Calis, G. Den Hartog, P.e.j. Van Erp, P C M Van De Kerkhof
    Abstract:

    The relevance of salicylic acid in Dithranol creams was evaluated in a double-blind study. Patients with chronic plaque psoriasis were treated using a short-contact schedule for Dithranol on an outpat

  • a comparison of twice daily calcipotriol ointment with once daily short contact Dithranol cream therapy a randomized controlled trial of supervised treatment of psoriasis vulgaris in a day care setting
    British Journal of Dermatology, 2006
    Co-Authors: P C M Van De Kerkhof, O.q.j. Swinkels, P.g.m. Van Der Valk, M. Kucharekova, M A De Rie, H J C De Vries, R J Damstra, A P Oranje, F B De Waardvan Der Spek, P Van Neer
    Abstract:

    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.

  • Dithranol irritation in psoriasis treatment: a study of 68 inpatients.
    Journal of The European Academy of Dermatology and Venereology, 2005
    Co-Authors: M. Kucharekova, P C M Van De Kerkhof, L. Lieffers, P.g.m. Van Der Valk
    Abstract:

    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.

P.g.m. Van Der Valk - One of the best experts on this subject based on the ideXlab platform.

  • Transepidermal water vapour loss is not increased during and following Dithranol irritation.
    British Journal of Dermatology, 2010
    Co-Authors: E. Snater, P.g.m. Van Der Valk, E.a.a.j. Janssen, P C M Van De Kerkhof
    Abstract:

    Dithranol is established as a very successful treatment for psoriasis. Its main disadvantages are irritation and staining at sites of application. The aim of the present study was to elucidate further the mechanism of Dithranol-induced irritation, in particular to what extent this is related to an impairment of the skin barrier. Dithranol 3% in cream, paste and petrolatum was applied to the forearm skin of 20 volunteers and left in situ for 1 h. Transepidermal water loss (TEWL) was measured during a period of 2 weeks following Dithranol application. In addition, a visual scoring system and colorimetry were used to assess erythema. The study showed conclusively that TEWL was not affected by the application of Dithranol, even though pronounced erythema occurred.

  • a comparison of twice daily calcipotriol ointment with once daily short contact Dithranol cream therapy a randomized controlled trial of supervised treatment of psoriasis vulgaris in a day care setting
    British Journal of Dermatology, 2006
    Co-Authors: P C M Van De Kerkhof, O.q.j. Swinkels, P.g.m. Van Der Valk, M. Kucharekova, M A De Rie, H J C De Vries, R J Damstra, A P Oranje, F B De Waardvan Der Spek, P Van Neer
    Abstract:

    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.

  • Dithranol irritation in psoriasis treatment: a study of 68 inpatients.
    Journal of The European Academy of Dermatology and Venereology, 2005
    Co-Authors: M. Kucharekova, P C M Van De Kerkhof, L. Lieffers, P.g.m. Van Der Valk
    Abstract:

    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.

  • Effectiveness and side effects of UVB‐phototherapy, Dithranol inpatient therapy and a care instruction programme of short contact Dithranol in moderate to severe psoriasis
    European Journal of Dermatology, 2004
    Co-Authors: O.q.j. Swinkels, P C M Van De Kerkhof, M. Prins, R.t. Veenhuis, T.m. De Boo, Marie-jeanne P. Gerritsen, G.j. Van Der Wilt, P.g.m. Van Der Valk
    Abstract:

    The efficacy of UVB-phototherapy (UVB) and Dithranol treatment for psoriasis is well established. However, well-conducted clinical trials on the efficacy of Dithranol are not available, making comparison between these time-honoured treatments with currently available therapies impossible. We studied the effectiveness of Dithranol in a care instruction programme using short time exposures (short contact treatment), UVB-phototherapy and Dithranol treatment in an inpatient setting. In an open randomised study we included 250 patients with moderate to severe psoriasis. The intention to treat group existed of 238 patients. 100 patients were treated with short contact Dithranol, 78 Patients were treated with UVB and 60 patients underwent inpatient Dithranol treatment. We found UVB and Dithranol treatment to be effective and safe in moderate to severe psoriasis. The efficacy of short contact Dithranol treatment equals the efficacy of UVB-phototherapy. Dithranol treatment at the inpatient department showed superior efficacy in clinical response rate and treatment duration as compared to UVB and short contact treatment. The median number of days in remission was significantly longer after short contact treatment as compared to inpatient treatment. Although the use of Dithranol is hampered by skin irritation and staining, the present study shows that Dithranol treatment has an outstanding efficacy and safety profile. Comparison between different antipsoriatic treatments should, besides clearing capacity, reconcile duration of remission, safety, patient acceptability and costs.

  • effectiveness and side effects of uvb phototherapy Dithranol inpatient therapy and a care instruction programme of short contact Dithranol in moderate to severe psoriasis
    European Journal of Dermatology, 2004
    Co-Authors: O.q.j. Swinkels, P C M Van De Kerkhof, M. Prins, R.t. Veenhuis, T.m. De Boo, Marie-jeanne P. Gerritsen, G.j. Van Der Wilt, P.g.m. Van Der Valk
    Abstract:

    The efficacy of UVB-phototherapy (UVB) and Dithranol treatment for psoriasis is well established. However, well-conducted clinical trials on the efficacy of Dithranol are not available, making comparison between these time-honoured treatments with currently available therapies impossible. We studied the effectiveness of Dithranol in a care instruction programme using short time exposures (short contact treatment), UVB-phototherapy and Dithranol treatment in an inpatient setting. In an open randomised study we included 250 patients with moderate to severe psoriasis. The intention to treat group existed of 238 patients. 100 patients were treated with short contact Dithranol, 78 Patients were treated with UVB and 60 patients underwent inpatient Dithranol treatment. We found UVB and Dithranol treatment to be effective and safe in moderate to severe psoriasis. The efficacy of short contact Dithranol treatment equals the efficacy of UVB-phototherapy. Dithranol treatment at the inpatient department showed superior efficacy in clinical response rate and treatment duration as compared to UVB and short contact treatment. The median number of days in remission was significantly longer after short contact treatment as compared to inpatient treatment. Although the use of Dithranol is hampered by skin irritation and staining, the present study shows that Dithranol treatment has an outstanding efficacy and safety profile. Comparison between different antipsoriatic treatments should, besides clearing capacity, reconcile duration of remission, safety, patient acceptability and costs.

O.q.j. Swinkels - One of the best experts on this subject based on the ideXlab platform.

  • a comparison of twice daily calcipotriol ointment with once daily short contact Dithranol cream therapy a randomized controlled trial of supervised treatment of psoriasis vulgaris in a day care setting
    British Journal of Dermatology, 2006
    Co-Authors: P C M Van De Kerkhof, O.q.j. Swinkels, P.g.m. Van Der Valk, M. Kucharekova, M A De Rie, H J C De Vries, R J Damstra, A P Oranje, F B De Waardvan Der Spek, P Van Neer
    Abstract:

    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.

  • Effectiveness and side effects of UVB‐phototherapy, Dithranol inpatient therapy and a care instruction programme of short contact Dithranol in moderate to severe psoriasis
    European Journal of Dermatology, 2004
    Co-Authors: O.q.j. Swinkels, P C M Van De Kerkhof, M. Prins, R.t. Veenhuis, T.m. De Boo, Marie-jeanne P. Gerritsen, G.j. Van Der Wilt, P.g.m. Van Der Valk
    Abstract:

    The efficacy of UVB-phototherapy (UVB) and Dithranol treatment for psoriasis is well established. However, well-conducted clinical trials on the efficacy of Dithranol are not available, making comparison between these time-honoured treatments with currently available therapies impossible. We studied the effectiveness of Dithranol in a care instruction programme using short time exposures (short contact treatment), UVB-phototherapy and Dithranol treatment in an inpatient setting. In an open randomised study we included 250 patients with moderate to severe psoriasis. The intention to treat group existed of 238 patients. 100 patients were treated with short contact Dithranol, 78 Patients were treated with UVB and 60 patients underwent inpatient Dithranol treatment. We found UVB and Dithranol treatment to be effective and safe in moderate to severe psoriasis. The efficacy of short contact Dithranol treatment equals the efficacy of UVB-phototherapy. Dithranol treatment at the inpatient department showed superior efficacy in clinical response rate and treatment duration as compared to UVB and short contact treatment. The median number of days in remission was significantly longer after short contact treatment as compared to inpatient treatment. Although the use of Dithranol is hampered by skin irritation and staining, the present study shows that Dithranol treatment has an outstanding efficacy and safety profile. Comparison between different antipsoriatic treatments should, besides clearing capacity, reconcile duration of remission, safety, patient acceptability and costs.

  • effectiveness and side effects of uvb phototherapy Dithranol inpatient therapy and a care instruction programme of short contact Dithranol in moderate to severe psoriasis
    European Journal of Dermatology, 2004
    Co-Authors: O.q.j. Swinkels, P C M Van De Kerkhof, M. Prins, R.t. Veenhuis, T.m. De Boo, Marie-jeanne P. Gerritsen, G.j. Van Der Wilt, P.g.m. Van Der Valk
    Abstract:

    The efficacy of UVB-phototherapy (UVB) and Dithranol treatment for psoriasis is well established. However, well-conducted clinical trials on the efficacy of Dithranol are not available, making comparison between these time-honoured treatments with currently available therapies impossible. We studied the effectiveness of Dithranol in a care instruction programme using short time exposures (short contact treatment), UVB-phototherapy and Dithranol treatment in an inpatient setting. In an open randomised study we included 250 patients with moderate to severe psoriasis. The intention to treat group existed of 238 patients. 100 patients were treated with short contact Dithranol, 78 Patients were treated with UVB and 60 patients underwent inpatient Dithranol treatment. We found UVB and Dithranol treatment to be effective and safe in moderate to severe psoriasis. The efficacy of short contact Dithranol treatment equals the efficacy of UVB-phototherapy. Dithranol treatment at the inpatient department showed superior efficacy in clinical response rate and treatment duration as compared to UVB and short contact treatment. The median number of days in remission was significantly longer after short contact treatment as compared to inpatient treatment. Although the use of Dithranol is hampered by skin irritation and staining, the present study shows that Dithranol treatment has an outstanding efficacy and safety profile. Comparison between different antipsoriatic treatments should, besides clearing capacity, reconcile duration of remission, safety, patient acceptability and costs.

  • an immunohistochemical assessment of the response of the psoriatic lesion to single and repeated applications of high dose Dithranol cream
    Skin Pharmacology and Applied Skin Physiology, 2002
    Co-Authors: O.q.j. Swinkels, M. Prins, P.g.m. Van Der Valk, M J P Gerritsen, I M J J Van Vlijmenwillems, P C M Van De Kerkhof
    Abstract:

    Dithranol, although a time-honoured treatment and from the beginning of the previous century still going strong, remains an empirical treatment. There is growing evidence that the biochemical basis for the mechanism of action of Dithranol at the molecular level is related to the redox activity leading to the production of active oxygen species, which include singlet oxygen, superoxide anion radical and hydroxyl radical. Some authors suggest that epidermal proliferation and/or keratinisation may be the target for Dithranol, while others refer to aspects of cutaneous inflammation as crucial in the antipsoriatic effect of Dithranol. The present study aims to analyse the effect of single and repeated applications of Dithranol on aspects of epidermal proliferation, keratinisation and inflammation in the psoriatic plaque. The most marked effect of Dithranol proved to be that on epidermal proliferation (the number of Ki-67-positive nuclei) with an early reduction already 1 day following the single application. This reduction lasted for 16 days. However, such an application induced only a modest clinical improvement. Repeated challenges, resulting in a decrease in the number of Ki-67-positive nuclei of 66%, led to a substantial clinical improvement after 12 days. Repeated challenges resulted in a significant reduction of the number of polymorphonuclear leucocytes. However, this reduction was less pronounced as compared to the effect on epidermal proliferation. It is concluded that epidermal proliferation is a sensitive marker to demonstrate an early effect of Dithranol. The dynamics of the cell-biological responses suggest that intermittent applications might be a promising new approach. As Dithranol does not reduce the number of T lymphocytes, it is attractive to speculate that the combination of Dithranol with immunosuppressive treatments might be a very effective combination.

  • The Response of Normal Human Skin to Single and Repeated Applications of Dithranol Cream: An Immunohistochemical Assessment
    Skin Pharmacology and Applied Skin Physiology, 2002
    Co-Authors: O.q.j. Swinkels, M. Prins, Marie-jeanne P. Gerritsen, P.g.m. Van Der Valk, L.w.j. Birker, P C M Van De Kerkhof
    Abstract:

    The irritative response of uninvolved skin is a serious limitation of Dithranol therapy in psoriasis. A characterisation in cell biological terms may be helpful in finding an effective counteraction to this well-known irritation. Therefore, we studied the effect of single and repeated applications of Dithranol on normal human skin. Besides a clinical evaluation, we studied aspects of epidermal proliferation, differentiation and inflammation. On day 2, after single Dithranol challenge, we observed an induction of both the cornified envelope precursor protein involucrin and the cross-linking enzyme transglutaminase I. Subsequently, epidermal hyperproliferation was observed with a maximum on day 8. The epidermal response to Dithranol appears to be a reinforcement of the barrier function. Remarkably, however, filaggrin was found to be decreased. Profilaggrin breakdown might be an attempt to compensate for xerosis of uninvolved skin that accompanies Dithranol therapy. T lymphocytes and to a lesser extent polymorphonucleocytes were found to be significantly increased. The reduction of Langerhans cells suggests a dose-dependent toxic effect of Dithranol or one of its metabolites on Langerhans cells. The dynamics in the induction of changes after repeated challenge are comparable with those after single challenge. However, the induction of hyperproliferation following repeated application appeared to continue between day 8 and 12. Based on the dynamics of Dithranol-induced irritation, it may be of interest to study the efficacy of intermittent Dithranol treatment. Our results indicate that an optimal timing for biopsies in future Dithranol irritation studies lies between 4 and 8 days after the first Dithranol challenge.

M. Prins - One of the best experts on this subject based on the ideXlab platform.

  • Effectiveness and side effects of UVB‐phototherapy, Dithranol inpatient therapy and a care instruction programme of short contact Dithranol in moderate to severe psoriasis
    European Journal of Dermatology, 2004
    Co-Authors: O.q.j. Swinkels, P C M Van De Kerkhof, M. Prins, R.t. Veenhuis, T.m. De Boo, Marie-jeanne P. Gerritsen, G.j. Van Der Wilt, P.g.m. Van Der Valk
    Abstract:

    The efficacy of UVB-phototherapy (UVB) and Dithranol treatment for psoriasis is well established. However, well-conducted clinical trials on the efficacy of Dithranol are not available, making comparison between these time-honoured treatments with currently available therapies impossible. We studied the effectiveness of Dithranol in a care instruction programme using short time exposures (short contact treatment), UVB-phototherapy and Dithranol treatment in an inpatient setting. In an open randomised study we included 250 patients with moderate to severe psoriasis. The intention to treat group existed of 238 patients. 100 patients were treated with short contact Dithranol, 78 Patients were treated with UVB and 60 patients underwent inpatient Dithranol treatment. We found UVB and Dithranol treatment to be effective and safe in moderate to severe psoriasis. The efficacy of short contact Dithranol treatment equals the efficacy of UVB-phototherapy. Dithranol treatment at the inpatient department showed superior efficacy in clinical response rate and treatment duration as compared to UVB and short contact treatment. The median number of days in remission was significantly longer after short contact treatment as compared to inpatient treatment. Although the use of Dithranol is hampered by skin irritation and staining, the present study shows that Dithranol treatment has an outstanding efficacy and safety profile. Comparison between different antipsoriatic treatments should, besides clearing capacity, reconcile duration of remission, safety, patient acceptability and costs.

  • effectiveness and side effects of uvb phototherapy Dithranol inpatient therapy and a care instruction programme of short contact Dithranol in moderate to severe psoriasis
    European Journal of Dermatology, 2004
    Co-Authors: O.q.j. Swinkels, P C M Van De Kerkhof, M. Prins, R.t. Veenhuis, T.m. De Boo, Marie-jeanne P. Gerritsen, G.j. Van Der Wilt, P.g.m. Van Der Valk
    Abstract:

    The efficacy of UVB-phototherapy (UVB) and Dithranol treatment for psoriasis is well established. However, well-conducted clinical trials on the efficacy of Dithranol are not available, making comparison between these time-honoured treatments with currently available therapies impossible. We studied the effectiveness of Dithranol in a care instruction programme using short time exposures (short contact treatment), UVB-phototherapy and Dithranol treatment in an inpatient setting. In an open randomised study we included 250 patients with moderate to severe psoriasis. The intention to treat group existed of 238 patients. 100 patients were treated with short contact Dithranol, 78 Patients were treated with UVB and 60 patients underwent inpatient Dithranol treatment. We found UVB and Dithranol treatment to be effective and safe in moderate to severe psoriasis. The efficacy of short contact Dithranol treatment equals the efficacy of UVB-phototherapy. Dithranol treatment at the inpatient department showed superior efficacy in clinical response rate and treatment duration as compared to UVB and short contact treatment. The median number of days in remission was significantly longer after short contact treatment as compared to inpatient treatment. Although the use of Dithranol is hampered by skin irritation and staining, the present study shows that Dithranol treatment has an outstanding efficacy and safety profile. Comparison between different antipsoriatic treatments should, besides clearing capacity, reconcile duration of remission, safety, patient acceptability and costs.

  • an immunohistochemical assessment of the response of the psoriatic lesion to single and repeated applications of high dose Dithranol cream
    Skin Pharmacology and Applied Skin Physiology, 2002
    Co-Authors: O.q.j. Swinkels, M. Prins, P.g.m. Van Der Valk, M J P Gerritsen, I M J J Van Vlijmenwillems, P C M Van De Kerkhof
    Abstract:

    Dithranol, although a time-honoured treatment and from the beginning of the previous century still going strong, remains an empirical treatment. There is growing evidence that the biochemical basis for the mechanism of action of Dithranol at the molecular level is related to the redox activity leading to the production of active oxygen species, which include singlet oxygen, superoxide anion radical and hydroxyl radical. Some authors suggest that epidermal proliferation and/or keratinisation may be the target for Dithranol, while others refer to aspects of cutaneous inflammation as crucial in the antipsoriatic effect of Dithranol. The present study aims to analyse the effect of single and repeated applications of Dithranol on aspects of epidermal proliferation, keratinisation and inflammation in the psoriatic plaque. The most marked effect of Dithranol proved to be that on epidermal proliferation (the number of Ki-67-positive nuclei) with an early reduction already 1 day following the single application. This reduction lasted for 16 days. However, such an application induced only a modest clinical improvement. Repeated challenges, resulting in a decrease in the number of Ki-67-positive nuclei of 66%, led to a substantial clinical improvement after 12 days. Repeated challenges resulted in a significant reduction of the number of polymorphonuclear leucocytes. However, this reduction was less pronounced as compared to the effect on epidermal proliferation. It is concluded that epidermal proliferation is a sensitive marker to demonstrate an early effect of Dithranol. The dynamics of the cell-biological responses suggest that intermittent applications might be a promising new approach. As Dithranol does not reduce the number of T lymphocytes, it is attractive to speculate that the combination of Dithranol with immunosuppressive treatments might be a very effective combination.

  • The Response of Normal Human Skin to Single and Repeated Applications of Dithranol Cream: An Immunohistochemical Assessment
    Skin Pharmacology and Applied Skin Physiology, 2002
    Co-Authors: O.q.j. Swinkels, M. Prins, Marie-jeanne P. Gerritsen, P.g.m. Van Der Valk, L.w.j. Birker, P C M Van De Kerkhof
    Abstract:

    The irritative response of uninvolved skin is a serious limitation of Dithranol therapy in psoriasis. A characterisation in cell biological terms may be helpful in finding an effective counteraction to this well-known irritation. Therefore, we studied the effect of single and repeated applications of Dithranol on normal human skin. Besides a clinical evaluation, we studied aspects of epidermal proliferation, differentiation and inflammation. On day 2, after single Dithranol challenge, we observed an induction of both the cornified envelope precursor protein involucrin and the cross-linking enzyme transglutaminase I. Subsequently, epidermal hyperproliferation was observed with a maximum on day 8. The epidermal response to Dithranol appears to be a reinforcement of the barrier function. Remarkably, however, filaggrin was found to be decreased. Profilaggrin breakdown might be an attempt to compensate for xerosis of uninvolved skin that accompanies Dithranol therapy. T lymphocytes and to a lesser extent polymorphonucleocytes were found to be significantly increased. The reduction of Langerhans cells suggests a dose-dependent toxic effect of Dithranol or one of its metabolites on Langerhans cells. The dynamics in the induction of changes after repeated challenge are comparable with those after single challenge. However, the induction of hyperproliferation following repeated application appeared to continue between day 8 and 12. Based on the dynamics of Dithranol-induced irritation, it may be of interest to study the efficacy of intermittent Dithranol treatment. Our results indicate that an optimal timing for biopsies in future Dithranol irritation studies lies between 4 and 8 days after the first Dithranol challenge.

  • The influence of a topical corticosteroid on short-contact high-dose Dithranol therapy.
    British Journal of Dermatology, 2001
    Co-Authors: O.q.j. Swinkels, M. Prins, Marie-jeanne P. Gerritsen, P.g.m. Van Der Valk, E.f.a. Tosserams, P C M Van De Kerkhof
    Abstract:

    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.

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  • therapeutic and cytotoxic effects of the novel antipsoriasis codrug naproxyl Dithranol on hacat cells
    Molecular Pharmaceutics, 2011
    Co-Authors: Wing Man Lau, Alex W White, Charles M Heard
    Abstract:

    A novel topical codrug, naproxyl–Dithranol (Nap-DTH), in which Dithranol and naproxen are linked via an ester in a 1:1 ratio to form a single chemical entity, was synthesized. The antiproliferative, anti-inflammatory and toxic effects of Nap-DTH were assessed, at the cellular level, using various in vitro methods. Cultured HaCaT keratinocytes were treated with Nap-DTH, and the cellular effects were compared with those of the parent compounds, individually and as a 1:1 mixture of naproxen:Dithranol to mimic 1:1 in situ liberation from Nap-DTH. The results demonstrate that Nap-DTH did not modify proliferation and only exhibited slight toxic effects after 24 h at concentrations >21 μM. At a lower concentration (3.4 μM), Nap-DTH did not alter cell proliferation or inflammation, which suggests that the codrug is therapeutically inert. Relating to this, the 1:1 mixture of naproxen:Dithranol exhibited the lowest toxic effect and the highest antiproliferative effect on HaCaT keratinocytes compared to Dithranol at the same concentration. Moreover, the 1:1 mixture exhibited a reduced inflammatory effect compared to Dithranol alone, as reflected by the upregulation of cyclooxygenase-2 by 45% and 136%, respectively. In spite of the 1:1 mixture showing a greater downregulation of Ki-67 and a 2-fold reduction of proliferating cell nuclear antigen (both cellular markers of proliferation) than Dithranol, Dithranol showed a much greater induction of cleaved caspase-3 protein expression (upregulated by 287%, compared to 85% for the 1:1 mixture). This suggests that when Dithranol was administered with naproxen, inhibition of cell growth plays a more important role in the antiproliferation effects than the induction of apoptotic cell death. These results confirm that the codrug would lead to a better therapeutic profile and fewer adverse effects compared to its parent compounds.

  • Topical Delivery of a Naproxen-Dithranol Co-drug: In Vitro Skin Penetration, Permeation, and Staining
    Pharmaceutical Research, 2010
    Co-Authors: Wing Man Lau, Alex W White, Charles M Heard
    Abstract:

    ABSTRACTPurposeThis work probed the topical delivery and skin-staining properties of a novel co-drug, naproxyl-Dithranol (Nap-DTH), which comprises anti-inflammatory (naproxen) and anti-proliferative (Dithranol) moieties.MethodFreshly excised, full-thickness porcine ear skin was dosed with saturated solutions of the compounds. After 24 h, the skin was recovered and used to prepare comparative depth profiles by the tape-stripping technique and to examine the extent of skin staining.ResultsDepth profiles showed that Nap-DTH led to a 5-fold increase in drug retention in the skin compared to Dithranol. The application of Nap-DTH also demonstrated improved stability, resulting in lower levels of Dithranol degradation products in the skin. Furthermore, significantly less naproxen from hydrolysed Nap-DTH permeated into the receptor phase compared to naproxen when applied alone (0.08 ± 0.03 nmol cm^-² and 180 ± 60 nmol cm^-², respectively). Moreover, the reduced staining of the skin was very apparent for Nap-DTH compared to Dithranol.ConclusionsTopical delivery of Nap-DTH not only improves the delivery of naproxen and Dithranol, but also reduces unwanted effects of the parent moieties, in particular the skin staining, which is a major issue concerning the use of Dithranol.

  • topical delivery of a naproxen Dithranol co drug in vitro skin penetration permeation and staining
    Pharmaceutical Research, 2010
    Co-Authors: Wing Man Lau, Alex W White, Charles M Heard
    Abstract:

    Purpose This work probed the topical delivery and skin-staining properties of a novel co-drug, naproxyl-Dithranol (Nap-DTH), which comprises anti-inflammatory (naproxen) and anti-proliferative (Dithranol) moieties.