Biomedical subjects

M Prins

Publications and source records attributed to M Prins.

79 records · Page 5Linked to original sources

PubMedDate not supplied

Dithranol in a cream preparation: disperse or dissolve?

In the search for the ideal dithranol cream preparation for short-contact treatment of psoriasis, we investigated the clinical efficacy, side effects and patient appreciation of two dithranol cream preparations (cream A and B) in a double-blind left-right comparing study. Dithranol was dissolved at preparation in cream A and dispersed in cream B. Cream A is known to have a shelf life of 1 year, while cream B has a much shorter shelf life (several months). Ten patients with chronic plaque-type psoriasis were treated during 7 weeks in a short-contact regimen. The clinical efficacy was monitored by scoring of erythema, induration, scaling and involved area (PASI); skin irritation was scored visually, and patient appreciation was evaluated by means of a multiple-choice questionnaire. Dispersion of dithranol in a cream was associated with less irritation and less discoloration of the skin, and its efficacy was comparable with that of the cream in which the dithranol was dissolved. As the dispersed dithranol formulation is easier to be manufactured, its quality will be less depending on the pharmacist's experience and equipment, and so more reliable. Besides, it will be less expensive to prepare. We advise to use this formulation for short-contact treatment.

Administration, Topical↗

PubMedDate not supplied

The response of normal human skin to single and repeated applications of dithranol cream: an immunohistochemical assessment.

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.

Administration, Cutaneous↗

PubMedDate not supplied

The response of uninvolved skin of patients with psoriasis to single and repeated applications of dithranol cream: an immunohistochemical assessment.

Dithranol is one of the most effective topical treatments for patients with psoriasis. The well-known irritation is a serious limitation. In an earlier study we investigated the inflammatory response to single and repeated applications with dithranol 2% cream in skin from healthy volunteers. In the present study, we assessed the clinical and cell-biological response of single and repeated challenges with dithranol 2% cream in uninvolved skin of patients with psoriasis. A striking difference between the two studies is the late phase in the single-challenge group after 8 days, showing a longer-lasting response in the uninvolved skin compared to normal skin with respect to proliferation and inflammation markers. A controlled and synchronised irritation by dithranol might induce anti-inflammatory processes and as such constitute an antipsoriatic principle. It is attractive to speculate that in psoriasis the induction of anti-inflammatory responses is defective. Following repeated applications of dithranol, a more uniform course of proliferation, differentiation and inflammation markers was observed in the uninvolved psoriatic skin as compared to the skin of healthy volunteers. Again a defect in the induction of anti-inflammatory responses might account for this event. In view of these differences between normal skin and psoriatic uninvolved skin, it may be advisable to use the uninvolved skin of patients with psoriasis in further studies on the interference between dithranol irritancy and various anti-inflammatory agents.

Administration, Topical↗

PubMedDate not supplied

An immunohistochemical assessment of the response of the psoriatic lesion to single and repeated applications of high-dose dithranol cream.

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.

Administration, Topical↗

PubMedDate not supplied

The effects of topical corticosteroids and a coal tar preparation on dithranol-induced irritation in patients with psoriasis.

Dithranol has been a mainstay in the treatment of psoriasis for more than 80 years. Although a safe approach, the irritation of the clinically uninvolved perilesional skin remains a major limitation of this treatment. Corticosteroids and coal tar solution have an anti-inflammatory potential. The aim of the present study was to investigate the clinical and cell-biological effects of two topical corticosteroids and a coal tar preparation on dithranol-irritated skin. During 4 consecutive days, 2% dithranol cream was applied to six uninvolved skin sites (3 cm in diameter) on the lower back of 9 patients with psoriasis. Dithranol was left on the skin for 1 h, subsequently removed with water and soap and the skin was dried with a towel. Subsequently, SITE 1 was treated with 0.05% clobetasol-17-propionate ointment (CP), SITE 2 with unguentum cetomacrogolis (vehicle 1), SITE 3 with 0.005% fluticasonpropionate ointment (FP), SITE 4 with 10% coal tar solution in lanettewax cream (CTS), SITE 5 was left untreated (control) and SITE 6 was treated with lanettewax cream (vehicle 2). Erythema, oedema and vesicle formation was scored every day. On day 5, punch biopsies were taken from the six sites. The expression of epidermal proliferation, differentiation and inflammation markers and the clinical irritation scores indicate that the application of a high potency corticosteroid (CP) is the best approach to minimise dithranol irritation, whereas CTS had virtually no effect on dithranol irritation during this 4-day experimental model.

Administration, Topical↗

PubMedDate not supplied

The impact of the frequency of short contact dithranol treatment.

Dithranol short contact treatment is usually applied once a day. For some patients this does not fit their possibilities or needs. Therefore we investigated the efficacy of two other treatment strategies in two small groups of patients. In the attempt to shorten the treatment time, one group of patients was treated twice daily. In order to not withhold short contact dithranol treatment from patients who are unable to perform the treatment daily or at home, a thrice-weekly treatment regimen was studied. 8 patients were treated twice daily and all achieved at least a 90% reduction of the area of involved skin (clearance) within 12.3 (+/- 1.6) weeks. In the thrice weekly group six out of eight patients achieved a clearance of their psoriasis within 13.1 (+/- 4.2) weeks. The aim of shortening the treatment period was not achieved by twice daily treatment in a day-care centre. However, the thrice-weekly treatment regimen certainly appeared to be an effective one. Further studies are needed on larger populations of patients to find out the optimal regimen for intermittent dithranol short contact treatment.

Administration, Cutaneous↗

PubMedDate not supplied

Effectiveness and side effects of UVB-phototherapy, dithranol inpatient therapy and a care instruction programme of short contact dithranol in moderate to severe psoriasis.

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.

Administration, Cutaneous↗