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.

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.

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.

A clinical and cardiovascular survey of Ehlers-Danlos syndrome patients with complete deficiency of tenascin-X.

BACKGROUND: We recently described a new autosomal recessive type of Ehlers-Danlos syndrome (EDS) based on a deficiency of the extracellular matrix protein tenascin-X (TNX). TNX-deficient patients have hypermobile joints, hyperextensible skin and show easy bruising. Because of the reported cardiovascular abnormalities in other EDS types and the excessive haematoma formation after mild trauma in TNX-deficient individuals, we investigated whether cardiovascular or coagulation abnormalities occur in these patients. METHODS: We examined seven TNX-deficient patients. One of them had a mitral valve prolapse and died postoperatively after valve replacement, before the study was completed. RESULTS: Bleeding time and coagulation factors (INR, APTT, PT and fibrinogen) were all within the normal range. Ultrasonographic examination of the carotid and femoral arteries showed normal vessel wall compliance and distensibility. Echocardiography showed a slight billowing of the mitral valve in two patients from one family. All patients had normal diameters of aortic root and ascending aorta. CONCLUSION: Although the patient group is small, there are no indications of generalised cardiovascular abnormalities in this type of EDS. We would recommend echocardiography for all these patients at the first evaluation and when a cardiac murmur appears.

A randomized comparison of an emollient containing skin-related lipids with a petrolatum-based emollient as adjunct in the treatment of chronic hand dermatitis.

Hand dermatitis is a multifactorial skin disorder in which skin barrier impairment is involved in the pathogenesis. The development of topical agents that improve skin barrier function is therefore a promising approach for the management of hand dermatitis. Topically applied lipids may interfere with skin barrier function, and emollients containing skin-related lipids have been suggested to facilitate repair of the skin barrier. However, evidence for the superiority of emollients containing skin-related lipids over the more traditional emollients is still lacking. The aim of this study was to compare an emollient containing skin-related lipids (Locobase Repair) with a traditional petrolatum-based emollient for the management of hand dermatitis. Adult males and females (n = 30) with mild to moderate chronic hand dermatitis were treated twice daily for 2 months either with an emollient containing skin-related lipids or with a pet.-based emollient. In the case of exacerbation, the patients of both treatment groups were allowed to use a mild corticosteroid according to instructions. Both treatment regimes significantly improved clinical signs of hand dermatitis as assessed by the investigator global assessment, hand eczema area and severity score. We did not observe significant differences in the improvement of clinical signs, itching, patients' assessment of efficacy, cosmetic acceptability or usage of topical corticosteroids between both treatment groups. In conclusion, this study confirms that the frequent use of emollients may be useful in the therapy of hand dermatitis. However, we could not demonstrate the superiority of this particular emollient containing skin-related lipids in patients with chronic hand dermatitis.

The effect of the PDE-4 inhibitor (cipamfylline) in two human models of irritant contact dermatitis.

BACKGROUND: New therapeutic approaches have to be considered in the treatment of irritant contact dermatitis (ICD). Recently, phosphodiesterase 4 (PDE-4) inhibitors have been introduced as nonsteroidal, antiinflammatory agents. These agents inhibit the secretion of the cytokines thought to be involved in the pathogenesis of ICD. We investigated the effect of a new selective PDE-4 inhibitor (cipamfylline) in human models using single and repeated exposures to an irritant in a blind, randomized pilot study with healthy volunteers. We compared the effect of cipamfylline ointment with a strong corticosteroid (betamethasone-17-valerate) and with a placebo ointment. METHODS: Ten volunteers were patch tested at four investigation sites with sodium dodecyl sulphate (1%) for 24 h. In a model that simulates chronic damage, 11 volunteers were patch tested with sodium dodecyl sulphate (0.2%) for 4 h daily for four consecutive days. The investigation sites were treated once a day with the above-mentioned agents. One site was left untreated. We used erythema scoring, measurements of transepidermal water loss (TEWL) and several immunohistochemical markers for epidermal proliferation and differentiation. RESULTS: Repeated application revealed that betamethasone-17-valerate caused a statistically significant reduction in erythema and TEWL compared to cipamfylline and placebo. We also observed a significant suppression of proliferating cells and cytokeratin 16 expression at sites treated with betamethasone compared to the other sites. In the model for acute ICD, no significant differences were seen between the investigated sites. CONCLUSIONS: Our results show that betamethasone-17-valerate may modulate the response in ICD. In this human model of ICD we could not confirm the efficacy of cipamfylline. Clinical studies are needed before the effect of PDE-4 inhibitors in ICD can be refuted with certainty.

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.

Effect of a lipid-rich emollient containing ceramide 3 in experimentally induced skin barrier dysfunction.

In the present study we compared the effect of a ceramide 3-containing emollient (Locobase(R) Repair) with a control emollient (vaselinum album/cremor lanette ana) and untreated damaged skin using clinical, bioengineering and immunohistochemical methods in two different models of experimentally induced skin barrier dysfunction. In model A (n = 13) skin barrier dysfunction was inflicted at three investigation sites by tape stripping. In model B (n = 13) the volunteers were patch tested at three investigation sites with sodium dodecyl sulphate (0.2%) for 4 h a day for 4 consecutive days. The investigation sites were treated once a day with the above-mentioned agents. Irritant reaction was assessed daily by erythema scoring and measurements of transepidermal water loss (TEWL). After 5D, punch biopsies were taken from all sites. Immunohistochemical assessment was carried out with respect to epidermal proliferation, epidermal differentiation and Langerhans cells. Tape stripping resulted in an erythematous reaction and an increase of TEWL associated with up-regulation of cycling cells, involucrin and expression of cytokeratin 16. At day 4, ceramide 3-containing emollient significantly decreased (p < 0.03) the erythema score, TEWL and cycling cells in comparison with the untreated site. Repetitive exposure to SDS induced a variable degree of erythema, gradual increase of TEWL, an increase of cycling cells, and up-regulation of involucrin, E-FABP and SKALP. The treatment with the control emollient significantly prevented erythema, increase of TEWL and cycling cells at day 4 compared to the untreated site. In summary, the present study demonstrated that both tested emollients improve skin barrier in different conditions compared to the untreated skin. There is some indication that formulations containing skin-related lipids might be of benefit in barrier disruption following tape stripping. Different models and clinical trials are needed to establish the usefulness in specific conditions of emollients containing skin-related lipids.

Combining lesional short-contact dithranol therapy of psoriasis with a potent topical corticosteroid.

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 lower and increased more slowly, suggesting a slower relapse rate with combination therapy. When comparing the follow-up data, it must be kept in mind that the three treatments showed an overall significantly different sum and area score at the start of follow up. CONCLUSIONS: Intermittent addition of clobetasol-17-propionate ointment enhanced the antipsoriatic efficacy of short-contact, high-dose dithranol therapy in terms of clearing capacity and treatment duration, without shortening remission duration.