Treatment Of Psoriatic Plaques Research Articles

Effect of TNF-α inhibitors on transcriptional levels of pro-inflammatory interleukin-33 and Toll-like receptors-2 and -9 in psoriatic plaques.

Tumor necrosis factor (TNF)-α inhibitors are considered to be effective in the treatment of psoriatic plaques, although the precise therapeutic pathway is not clear. Pro-inflammatory molecules, such as Toll-like receptor (TLR)-2 and -9 and interleukin (IL)-33, a member of the IL-1 receptor/TLR superfamily, have been found to be expressed in psoriatic plaques. The aim of the present study was to investigate whether TNF-α inhibitor treatment has an effect on the expression of IL-33 and TLR-2 and -9 in psoriatic plaques. Seventeen patients with psoriatic plaques were treated with a TNF-α inhibitor (etanercept or infliximab) for 12 weeks in an open-label study, and the transcriptional levels of IL-33 and TLR-2 and -9 were determined by reverse transcription-quantitative polymerase chain reaction in paired biopsies of psoriatic plaques obtained at baseline (B) and following the 12 weeks of treatment (P). The psoriasis area severity index (PASI) score was also determined. At B, elevated IL-33 and TLR-2 mRNA levels were observed in all cases, while TLR-9 showed elevated mRNA levels in 76% of cases. At P, reductions in the mRNA levels of IL-33, TLR-2 and TLR-9 were observed, with TLR-2 and -9 levels exhibiting significant reductions (P<0.0001, Wilcoxon signed-rank test). PASI scores were significantly reduced by the treatment (P<0.0001, Wilcoxon signed-rank test) and the changes in PASI scores exhibited a significant positive Pearson's correlation with the P/B mRNA expression ratios of TLR-2 or -9 in males (P<0.05), particularly in the etanercept group (P<0.0001). The findings support the efficacy of anti-TNF-α treatment on the innate immune response in psoriatic skin, with a focus on TLR-2 and -9 inhibition, suggesting their role in the pathogenic mechanism of plaque psoriasis, which may be associated with gender.

Effects of tissue-tolerable plasma on psoriasis vulgaris treatment compared to conventional local treatment: A pilot study

The effect of tissue-tolerable plasma (TTP) on inflammatory diseases such as psoriasis was investigated. Three plaques of six psoriatic patients were subjected to different treatments (A: TTP, brine baths (BB)+5% salicylic acid ointment (SAO); B: BB+SAO; C: BB, UV irradiation, SAO+dithranol). While redness and infiltration was reduced in groups A and C, scaling was reduced in group C. TTP temporarily reduced the bacterial colonization on the skin lesions. In summary, the treatment of psoriatic plaques with TTP showed no significant advantage over conventional therapies.

Vitamin D Analog Calcipotriol Suppresses the Th17 Cytokine–Induced Proinflammatory S100 “Alarmins” Psoriasin (S100A7) and Koebnerisin (S100A15) in Psoriasis

The antimicrobial peptides (AMP) psoriasin (S100A7) and koebnerisin (S100A15) are differently induced in psoriatic skin. They act synergistically as chemoattractants and "alarmins" to amplify inflammation in psoriasis. Th17 cytokines are key players in psoriasis pathogenesis and vitamin D analogs feature anti-psoriatic effects; both of these activities could be mediated through epidermal AMP regulation. We show that supernatants of cultured psoriatic T cells induce and release psoriasin and koebnerisin from keratinocytes and the Th17 cytokines IL-17A, tumor necrosis factor-α, and IL-22 differently regulate psoriasin and koebnerisin reflecting their distinct expression pattern in normal and psoriatic skin. IL-17A is the principal inducer of both S100 and their expression is further amplified by cooperating Th17 cytokines in the micromilieu of psoriatic skin. Increased extracellular psoriasin and koebnerisin also synergize as "alarmins" to prime epidermal keratinocytes for production of immunotropic cytokines that further amplify the inflammatory response. Treatment of psoriatic plaques with the vitamin D analog calcipotriol interferes with the S100-mediated positive feedback loop by suppressing the increased production of psoriasin and koebnerisin in psoriatic skin and their Th17-mediated regulation in epidermal keratinocytes. Thus, targeting the S100-amplification loop could be a beneficial anti-inflammatory approach in psoriasis and other inflammatory skin diseases.

Successful treatment of psoriatic plaques, including psoriatic scalp lesions, with wavelength optimized UV-B from a short arc light source

Successful treatment of psoriatic plaques, including psoriatic scalp lesions, with wavelength optimized UV-B from a short arc light source

Efficacy of Calcipotriol Ointment Applied under Hydrocolloid Occlusion in Psoriasis

Background: Hydrocolloid (HCD) dressings enhance the efficacy of topical corticosteroids. Objective: We wanted to evaluate the effect of calcipotriol ointment under an HCD dressing in the treatment of psoriatic plaques. Methods: In 9 psoriatic patients, we cleared one plaque using this approach and took biopsies at start, clearance and relapse. Clinical and immunohistochemical validation was assessed. Results: After an average treatment of 3.6 weeks, each lesion had cleared (apart from some residual erythema). The average remission period was 8 weeks. During this treatment, the number of cycling epidermal cells (Ki-67-positive nuclei) and the expression of keratin 14 and keratin 16 had decreased substantially. In biopsies taken from the skin immediately adjacent to the relapsing lesion, these markers remained reduced which indicated the prolonged effect of calcipotriol on epidermal differentiation. Conclusion: It is speculated that combination therapy of calcipotriol with treatments with a different mode of action such as photo(chemo)therapy, corticosteroids and cyclosporine might be worthwhile.

Proliferation is the main epidermal target in the treatment of psoriatic plaques with once daily application of tacalcitol ointment.

We studied the effect of tacalcitol (1 alpha, 24 dihydroxy vitamin D3) ointment on clinical and immunohistochemical efficacy in psoriatic patients during 2 months of treatment. The psoriasis area and severity index decreased significantly after only 1 month and the total body surface index decreased 55% after 2 months. To characterize the epidermal compartment keratin 14, keratin 16, epidermal growth factor receptor, apoptotic and Ki-67 positive cells were examined. After 1 week of treatment no significant changes were found in any of these parameters. After 2 months, keratin 16 reached the levels observed in normal skin and Ki-67 and keratin 14 expression also reduced significantly. Epidermal growth factor receptor staining and the number of apoptotic cells did not alter during treatment. We conclude that tacalcitol is effective in the treatment of plaque psoriasis. Because the main epidermal effect observed immunohistochemically is a reduction in proliferation, a combination therapy using either corticosteroids, vitamin A derivatives or dithranol seems rational.

Clobetasol under Hydrocolloid Occlusion in Psoriasis Results in a Complete Block of Proliferation and in a Rebound of Lesions following Discontinuation

Background: It is a well-established fact that very potent corticosteroids are highly effective in the treatment of psoriatic plaques, and that the addition of a hydrocolloid occlusive dressing (HCD) enhances its efficacy. It is known that topical steroids induce normal differentiation and diminish hyperproliferation during treatment of psoriatic plaques. These changes are reflected by an increase in keratin 10 (K10) and a decrease in keratin 6 (K6), respectively. However, the influence of class IV corticosteroids under HCD on K10 and K6 subpopulations has never been studied. Objective: The present study was performed to study quantitatively the influence of a class IV topical steroid under HCD on the dynamics of K10 and K6 subpopulations. Methods: In the present study, we treated moderately severe stable psoriatic plaques with clobetasol-17-propionate under HCD until clearance was achieved. We took biopsies prior to treatment, after clearance and at relapse. Using flow cytometry, we studied the dynamics of K10 and K6 subpopulations. Results: Prior to treatment, 41.8% of all cells expressed K6. After treatment-induced clearance, this proportion decreased to 1.2%, which is below the normal range. At relapse, pre-treatment levels were observed again. A trend to an increasing number of basal cells and an increase in the proliferative activity of these basal cells at relapse compared to the stable situation prior to treatment was observed. Conclusion: We conclude that clobetasol under hydrocolloid occlusion induces virtually a total block of proliferation of the basal cell population and decreases hyperproliferation-associated keratins dramatically. Furthermore, based upon epidermal cell characteristics, we conclude that a rebound phenomenon occurs following discontinuation of therapy with clobetasol under hydrocolloid occlusion.

The epidermis as a target for antipsoriatic treatment

The modes of action of antipsoriatic treatments can be studied in in vitro in models, in vivo models or during treatment of psoriatic plaques. During the last decade research programmes in Nijmegen have focused on the epidermis as a target for antipsoriatic treatments. The present communication reviews aspects of epidermal growth and inflammation during the treatment of psoriasis. Both in vitro and in vivo data are reviewed. All established antipsoriatic treatments have been proved to inhibit epidermal proliferation in vitro and in vivo, except for cyclosporin. Cyclosporin is a selective immunomodulatory treatment in vivo. In contrast to the in vitro situation, during treatment of psoriatic plaques in vivo a rather consistent pattern is observed for all antipsoriatic treatments with a reduction of involucrin-, transglutaminase-and keratin 16-positive cell layers and an increase in the number of filaggrin-positive cell layers. The various antipsoriatic treatments differ mainly with respect to the modulation of cutaneous inflammation. Based on cell-biological observations some combinations of treatments can be expected to be highly effective clinically. The combination of immuno-modulating treatments with predominantly growth-inhibitory and keratinization-modulating treatments is promising. From a cell-biological point of view, highly successful combinations are the combination of dithranol and phototherapy and the combination of cyclosporin and calcipotriol.

Topical treatment of psoriatic plaques with 1 alpha, 24 dihydroxyvitamin D3: a multiparameter flow cytometrical analysis of epidermal growth, differentiation and inflammation.

The clinical efficacy and tolerability of the vitamin D3 analogues calcitriol, calcipotriol and 1 alpha, 24 dihydroxyvitamin D3 in the treatment of psoriasis have been assessed in various clinical studies. In vitro and in vivo investigations have shown interference of these compounds with epidermal growth, keratinisation and inflammation. In this study we quantified the in vivo cell biological effects during treatment of psoriatic plaques with 1 alpha, 24 dihydroxyvitamin D3. By using a flow cytometric triple labelling procedure, we could discriminate different epidermal subpopulations, permitting precise assessment of epidermal cell cycle kinetics. Twenty patients with plaque-type psoriasis were treated in a double-blind placebo-controlled left-right comparative study with 1 alpha, 24 dihydroxyvitamin D3 ointment (4 micrograms/g applied once daily) for 8 weeks. Epidermal cell suspensions prepared from keratotome biopsies taken before and after treatment were stained with TO-PRO-3 iodide (a new DNA fluorochrome) and monoclonal antibodies against keratin 10 (as a marker for differentiation) and vimentin (as a marker for inflammation), simultaneously. The flow cytometric analyses showed a significant decrease of proliferating basal keratinocytes in verum-treated lesions, whereas such a decrease was not observed in placebo-treated lesions. The amount of keratin 10-positive keratinocytes increased and the presence of vimentin-positive cells decreased in cell suspensions derived from both verum- and placebo-treated lesions, but these effects were not significant. We conclude that multiparameter flow cytometry promises to be an adequate approach to assess the interference of antipsoriatic treatments with cutaneous inflammation, epidermal proliferation and keratinisation. Topical 1 alpha, 24 dihydroxyvitamin D3 seems to exert its in vivo antipsoriatic effect mainly through an inhibition of epidermal growth.

Occlusive hydrocolloid dressings decrease keratinocyte population growth fraction and clinical scale and skin thickness in active psoriatic plaques

Clinical studies suggest a therapeutic role for occlusion in the treatment of psoriasis. Previous studies, using multiparameter RNA DNA flow cytometric analysis of epidermal suspensions obtained from active plaques, demonstrated increased keratinocyte growth fraction which reversed with successful medical treatment. Because keratinocyte growth fraction reflected disease activity, it was used in this study in addition to clinical evaluations in order to determine the efficacy of occlusion in the treatment of psoriatic plaques. In each of 9 patients, scale, skin thickness and erythema were compared in one occluded and one control plaque using an analog scale. Both scale and skin thickness, but not erythema, were decreased after 2 weeks of occlusion. However after 10 weeks, no additional differences were seen when compared with assessments made after 2 weeks, suggesting that the benefits of occlusive therapy occurred early. After 10 weeks of occlusion, the keratinocyte growth fraction was significantly decreased in occluded plaques. This study demonstrates that occlusion plays a synergistic role with other therapeutic modalities in ameliorating psoriatic plaques.

Metabolic changes in the psoriatic lesion during therapy.

Three marker enzymes were measured during treatment of psoriatic plaques with two different therapies. During treatment with clobetasol propionate the epidermal enzymes (acid phosphatase and glucose-6-phosphate dehydrogenase) returned to normal within 14 days whereas capillary alkaline phosphatase remained at the original level. By contrast, all three marker enzymes reverted to normal at the same tempo during PUVA therapy, reaching the control range after 4-8 weeks.

A human model system for the release of endogenous inhibitor(s) of prostaglandin biosynthesis

The evolving vesicular patch test reaction served as a huma model for immunologically induced epidermal damage. We observed that inhibitory factor(s) were detectable in the homogenates only after epidermal disruption had appeared. Maximum inhibition correlated with acute changes seen histologically in the evolving patch test reaction. During resolution of the patch test reaction, the presence of inhibitory factor(s) in the skin homogenates became undetectable. A white ring similar to the Woronoff ring described after ultraviolet light and coal tar therapy of psoriatic plaques was reproduced surrounding the vesicular patch test reaction, suggesting that the inhibitory substance(s) detected following epidermal trauma of various types (physical, immunologic, inflammatory, etc.) functioned in vivo in a similar fashion. Our results suggests that Woronoff's ring is a nonspecific phenomenon that can be formed following various types of trauma to the skin rather than a specific occurrence associated only with the treatment of psoriatic plaques.

The intralesional use of triamcinolone acetonide in psoriasis. A double blind study.

The effectiveness of the treatment of psoriatic lesions by the intralesional injections of triamcinolone acetonide has been demonstrated by many investigators. 1-3 In a double blind study of psoriatic patients triamcinolone acetonide by intralesional injection was indeed found to be effective in clearing the lesion of psoriasis. Its efficacy was markedly greater than hydrocortisone or prednisolone tertiary butyl acetate. Material and Method All patients in this study were hospitalized and had no other form of systemic or topical therapy. In order to avoid the possibility of systemic effect the amount of triamcinolone acetonide injected was limited to 0.2 ml. of 1% suspension. The control material was the vehicle alone to which hydrocortisone acetate was added to make a 0.4% suspension to simulate the cloudy appearance of the triamcinolone acetonide suspension. Hydrocortisone acetate in this concentration was found to be totally ineffective in the treatment of psoriatic plaques. The suspensions were