Barrier repair in chronic plaque-type psoriasis

Purpose: To investigate barrier repair after mild trauma in lesional skin of psoriasis patients with chronic plaque-type disease and to compare this with non-involved psoriatic skin and normal controls.
Methods: Transepidermal water loss (TEWL) readings were taken from involved psoriatic skin and non-involved skin of psoriasis patients as well as the skin of normal controls. Three readings were performed at each site: the basal state, immediately after 20 tape strippings and 1 week post stripping.
Results: Higher baseline, post-stripping and 1-week recovery TEWL readings in psoriatic-involved skin compared to non-involved and normal control skin. No significant difference in barrier recovery rate in psoriatic-involved skin compared to non-involved and normal control.
Conclusion: Although there appears to be a derangement of barrier function in lesional skin of psoriasis patients compared to non-lesional skin and the skin of healthy controls, the barrier recovery function of lesional psoriatic skin is still fully operational.     

Short-term cyclosporin monotherapy for chronic severe plaque-type psoriasis

Cyclosporin is an effective treatment for psoriasis but its efficacy is only palliative. The aim of this study was to evaluate the percentage of patients in whom a short term therapy may be used without relapse after discontinuation of cyclosporin. In this multicenter, open, non-controlled study fifty-eight patients were included who had severe and extensive chronic plaque-type psoriasis. Treatment duration was 28 weeks. The absence of relapse was defined as the requirement to resume systemic treatment at 16 weeks after discontinuation of Sandimmun .The overall efficacy of Sandimmun at W20 was 72%. No relapse or premature withdrawal occurred in 18 cases out of 39 (47%). In these cases local treatment was sufficient following discontinuation. Thus we show the potential value of a single 5 month course of cyclosporin treatment. In this study tapering of cyclosporin was not useful. In 50% of cases short-term cyclosporin treatment was not followed by resumption of systemic treatment and constitutes an improvement in qualify of life.     

Erythrocyte glutathione peroxidase activity and plasma vitamin E status in patients with psoriasis

Erythrocyte selenium dependent glutathione peroxidase (GSH-Px) activity and plasma vitamin E levels were measured in 20 psoriatics. Psoriatics had significantly lower GSH-Px and plasma vitamin E levels than did controls. Psoriatics were divided into three grades by the rule of nine: Grade I—less than 33% skin involvement, Grade II—33-66%, and Grade III—over 66% skin involvement. Grade III psoriatics showed much lower values of GSH-Px and plasma vitamin E, showing a definite correlation with the percentage of surface area involved.     

The psoriasis area and severity index is the adequate criterion to define severity in chronic plaque-type psoriasis

BACKGROUND: Chronic plaque-type psoriasis is a major dermatosis, but a significant question is still unanswered: What defines severity in chronic plaque-type psoriasis? While objective assessments like the Psoriasis Area and Severity Index (PASI) have frequently been used in clinical trials, quality of life (QOL) questionnaires are currently becoming more and more popular. OBJECTIVE: This article summarizes the most important objective and subjective measurements of severity in psoriasis. For every dermatologist it is critically important to distinguish between severe psoriasis and psoriasis that severely affects QOL. Even if the PASI also has disadvantages, it is the most adequate instrument available to evaluate severity in plaque-type psoriasis. RESULT: We provide reasons why PASI >12 defines severe, PASI 7-12 moderate and PASI <7 mild chronic plaque-type psoriasis.     

Increased chemotactic activity of neutrophil leukocytes in psoriasis

The random and active migration of neutrophil leukocytes in agarose was studied in sixty-one patients with psoriasis and in healthy controls. E. coli filtrate was used as chemoattractant. The random as well as the active migration was increased in psoriasis. The increase was most pronounced in those cases with widespread psoriasis. In twenty patients who were followed for 1–3 years, the neutrophil chemotactic activity remained essentially unchanged.     

Programmed cell death of keratinocytes in infliximab-treated plaque-type psoriasis

BACKGROUND: Tumour necrosis factor (TNF)-alpha blockade using infliximab, a chimeric anti-TNF-alpha antibody, is an effective treatment for plaque-type psoriasis, inducing remission in about 80% of patients. OBJECTIVES: To examine infliximab-induced programmed cell death (PCD) of keratinocytes in psoriatic plaques on serial skin biopsy samples. METHODS: Five patients with moderate to severe plaque-type psoriasis received infliximab infusions intravenously (5 mg kg(-1)) at weeks 0, 2 and 6. Biopsies of nonlesional and lesional skin (days 0, 5, 14 and 21) were obtained. Conventional microscopy was used to examine the morphology of the psoriatic keratinocytes. In situ detection of apoptosis was performed by electron microscopy and by immunohistochemical staining with anti-p53 and anti-caspase-3 antibodies. Results Infusion of infliximab induced a clinical response in all five patients with psoriasis, with a mean Psoriasis Area and Severity Index improvement of 24.8% already at day 5. This was accompanied by significant histopathological changes in the skin biopsy samples after infliximab treatment. Light and electron microscopic evaluation revealed apoptosis-like morphological changes in lesional keratinocytes, i.e. nuclear condensation, chromatin fragmentation and cytoplasmic vesiculation, visible already after the first infusion. These damaged keratinocytes stained positively for p53, but not for active caspase-3. CONCLUSIONS: The effects of infliximab in psoriasis extend beyond merely anti-inflammatory actions, and may include caspase-independent PCD of lesional keratinocytes. The PCD of keratinocytes may be an important mechanism that could explain at least in part the rapid and sustained therapeutic effect of infliximab in psoriasis.     

Efficacy of a far erythemogenic dose of narrow-band ultraviolet B phototherapy in chronic plaque-type psoriasis

The aim of the present study was to examine the effect of far erythemogenic dose of narrow-band ultraviolet B (NB-UVB; starting dose at 35% minimal erythematous dose [MED]) on clinical response by measuring the severity, extent of disease and the changes in quality of life. Fifty patients with chronic plaque-type psoriasis were enrolled. Therapy was held for 3 days a week. The severity of the disease was assessed based on the Psoriasis Area and Severity Index (PASI) score and Dermatology Life Quality Index (DLQI) scores. The percentage improvement of PASI at 30 sessions was 68.99%. The improvement in DLQI scores at 30 sessions was 79.67%. Pearson correlation coefficients showed that PASI scores were not correlated with DLQI scores at the beginning of treatment ( P  = 0.330, r  = 0.14), but after the 30th session of NB-UVB therapy improvements in quality of life were correlated ( P  < 0.05, r  = 0.399). Therefore, far erythemogenic dose of NB-UVB is considered to be effective treatment for plaque-type psoriasis in our patients. However, we cannot confirm that it is safer than higher MED starting dose in term of cumulative UV irradiation.     

Narrowband UV-B phototherapy vs photochemotherapy in the treatment of chronic plaque-type psoriasis: a paired comparison study.

OBJECTIVE: To compare the therapeutic efficacy of narrowband (TL-01) UV-B phototherapy vs photochemotherapy (psoralen-UV-A [PUVA]) in patients with chronic plaque-type psoriasis. DESIGN: Open, nonrandomized, intraindividually controlled paired comparison study. SETTING: Phototherapeutic unit in a university hospital. PATIENTS: Twenty-five patients with chronic plaque-type psoriasis. INTERVENTIONS: Paired irradiations with threshold erythemogenic doses of narrowband UV-B and PUVA were given to the patients' dorsal aspect including the arms and legs. Treatment was performed 3 times weekly until complete or almost complete clearing with one or both regimens or over a maximum period of 18 exposures. MAIN OUTCOME MEASURES: Assessment of the Psoriasis Area and Severity Index (PASI) in each half of the patient's dorsal aspect before and after treatment with the 2 regimens. RESULTS: The median pretreatment PASI score of 16 (range, 6.2-23.4) was reduced by 84% to 2.5 (range, 0-12.6) by the narrowband UV-B treatment and by 89% to 1.8 (range, 0-8.2) by the PUVA treatment. Statistical analysis of these data showed a tendency for PUVA being superior to narrowband UV-B although the difference remained below the level of significance (P = .17). However, a clear effect of the pretreatment PASI score on the therapeutic outcome was found. Patients with higher baseline PASI scores responded significantly better to PUVA than to narrowband UV-B (P = .03). CONCLUSIONS: Our data demonstrate that in many patients with plaque-type psoriasis, narrowband UV-B is comparably as effective as PUVA and, given the lack of photosensitizer-related adverse reactions and the possibly lower long-term cancer risk, can be considered as first-line treatment. Treatment with PUVA, on the other hand, remains the mainstay for patients with high PASI scores who do not respond or whose psoriasis cannot be controlled adequately by narrowband UV-B.     

Decreased specific anti-elastase activity in the uninvolved skin of patients with psoriasis

Summary Inhibitory activities against elastase, chymotrypsin and trypsin were studied in the fluid from experimentally developed suction blisters in the uninvolved skin of patients with psoriasis. These activities determined by spectrophotometry of specific synthetic low molecular weight substrates were compared with respective antiproteinase activities in sera of 32 patients with psoriatic lesions, ten patients in remission, and ten healthy volunteers. A marked reduction (29.2%) in the specific elastase inhibitory activity of blister fluid was found in patients with psoriasis when compared with normal subjects (p<0.05), since neither chymotrypsin nor trypsin inhibitory activities were altered. This reduction was despite about a 30% increase in the elastase inhibitory activity in the sera of these patients, which was related presumably to their increased activity of ₁-proteinase inhibitor, the main serum antiserine proteinase inhibitor. A decreased blister fluidserum elastase inhibition ratio was shown in a large majority of patients with psoriasis, even in symptomless patients. The deficiency in specific elastase inhibitory activity of suction blister fluid was predominantly associated with early onset of psoriasis, guttate lesions and inactive lesions, skin involvement less than 20% of body surface, duration of relapse shorter than 2 months, and frequent relapses. These data indicate that the uninvolved skin of patients with psoriasis contains low concentrations of specific elastase tissue inhibitor, which deficiency might result in an excessive in vivo hydrolytic activity of neutrophil elastase released from migrating cells in the psoriatic skin.     

Clobetasol propionate lotion in the treatment of moderate to severe plaque-type psoriasis

Owing to its anti-inflammatory, antipruritic, vasoconstrictive, and immune-modulating properties, clobetasol propionate is used to treat psoriasis. This study was conducted to evaluate the efficacy, safety, and cosmetic acceptability of clobetasol propionate lotion compared with its vehicle and with clobetasol propionate cream in the treatment of moderate to severe plaque-type psoriasis. A total of 222 patients were treated. After 4 weeks of treatment, clobetasol propionate lotion was more efficient than vehicle lotion and of equivalent efficacy as clobetasol propionate cream. Cosmetic acceptability was significantly better with clobetasol propionate lotion than with clobetasol propionate cream. Clobetasol propionate lotion was efficient, safe, and well tolerated and offers a significantly higher cosmetic advantage in the treatment of moderate to severe plaque-type psoriasis compared with clobetasol propionate cream.     

Oral R115866 in the treatment of moderate to severe plaque-type psoriasis

BACKGROUND: R115866 (Rambazole) is a new generation all-trans retinoic acid metabolism blocking agent, highly specific against the retinoic acid 4-hydroxylase. The drug alleviates hyperproliferation and normalizes differentiation of the epidermis in animal models of psoriasis. OBJECTIVE: To explore the efficacy, safety and tolerability of systemic R115866 in patients with moderate to severe plaque-type psoriasis. PATIENTS AND METHODS: In this open label, single-arm trial, patients were treated with R115866, 1 mg/day for 8 weeks, followed by a 2-week treatment-free follow-up period. Patients were monitored for efficacy and safety. RESULTS: Nineteen patients (intent-to-treat population) were treated and 14 completed the entire study. Two patients discontinued due to lack of efficacy and three due to adverse events. At the end of the treatment, 26% of the patients showed at least 50% reduction in Psoriasis Area Severity Index (PASI) compared to baseline. Further improvement was observed at the end of the 2-week follow-up period where 47% of the patients showed a 50% or greater reduction in PASI. Kinetic data showed no evidence of accumulation of either R115866 or retinoic acid in plasma. The most common adverse events were pruritus, xerosis, cheilitis and an increase in blood triglycerides. The majority of adverse events were mild to moderate. No deaths or serious adverse events were reported. CONCLUSION: Eight-week daily treatment with 1 mg R115866 resulted in a significant reduction in PASI from baseline to end of therapy. Additional improvement was seen after the 2-week follow-up period. The drug was well tolerated. R115866 merits further evaluation to optimize its clinical efficacy and safety profile in moderate to severe plaque-type psoriasis.     

Vascularity and fractal dimension of the dermo-epidermal interface in guttate and plaque-type psoriasis

BACKGROUND: Histological structures of the skin are often irregular in size and shape. Euclidean geometry and fractal analysis are complementary for assessing distinct aspects of their dimensions. OBJECTIVE: To determine and compare the variations in shape of the dermo-epidermal junction and the size of the superficial vessels in psoriatic lesions. METHOD: The relative microvasculature area and the fractal dimension D of the dermo-epidermal interface were measured inside and outside growth-stunted guttate lesions (n = 22) and expanding plaques (n = 37) in psoriasis of the trunk. RESULTS: The median D values of the dermo-epidermal interface were significantly larger (p < 0.01) in psoriatic plaques (D = 1.15) than in guttate lesions (D = 1.08), and these D values on lesional skin were significantly larger (p < 0.01) than in the uninvolved skin (D = 1.03). The microvasculature was significantly (p < 0.01) more developed in lesional (plaque: 13%, guttate: 8.20%) than in uninvolved skin (3.60 and 3.85%). No correlations were found between the relative microvasculature areas and the D values of the dermo-epidermal interface, both in the uninvolved and lesional skins of each psoriatic type. CONCLUSION: The absence of a relationship between modulations of the dermo-epidermal junction and vascular hyperplasia, both in expanding and stable psoriasis lesions, suggests that these events are regulated by different mechanisms and do not depend on each other.     

Failure of short-term psoralen and ultraviolet A light maintenance treatment to prevent early relapse in patients with chronic recurring plaque-type psoriasis

Background: Photochemotherapy using psoralen and ultraviolet A light (PUVA) is a highly effective treatment option for patients with severe psoriasis. Maintenance treatment has been advocated to provide for sustained remission. However, only a few studies have been conducted to assess the efficacy of maintenance treatment and these have provided inconsistent results.
Methods: We performed a prospective intrapatient left–right comparison study in 34 patients with chronic relapsing plaque psoriasis. PUVA treatment for clearing was given four times weekly. After complete or near-complete clearing, all patients were placed on a halfside maintenance schedule with irradiation twice weekly and then once weekly for 4 weeks each. The psoriasis area and severity index score was determined at baseline, end of the clearing phase and at 2-monthly intervals after discontinuation of treatment.
Results: Using a short-term maintenance protocol, a moderate delay in relapse of psoriasis was observed in only three patients (8.8%; 95% CI: 1.8–23.6%). In the remaining patients (91.2%), maintenance treatment had no effect on the length of remission. The mean time interval until relapse without and with maintenance irradiation was 4.5 ± 3.4 and 4.6 ± 3.4 months, respectively.
Conclusion: Our data indicate that short-term maintenance treatment is not effective in preventing early relapse of psoriasis and should be avoided.