Lesions In Psoriatic Patients Research Articles

Sensory neurons increase keratinocyte proliferation through CGRP release in a tissue engineered in vitro model of innervation in psoriasis

Skin denervation has been shown to cause remission of psoriatic lesions in patients, which can reappear if reinnervation occurs. This effect can be induced by the activation of dendritic cells through sensory innervation. However, a direct effect of nerves on the proliferation of keratinocytes involved in the formation of psoriatic plaques has not been investigated. We developed, by tissue engineering, a model of psoriatic skin made of patient skin cells that showed increased keratinocyte proliferation and epidermal thickness compared to healthy controls. When this model was treated with CGRP, a neuropeptide released by sensory neurons, an increased keratinocyte proliferation was observed in the psoriatic skin model, but not in the control. When a sensory nerve network was incorporated in the psoriatic model and treated with capsaicin to induce neuropeptide release, an increase of keratinocyte proliferation was confirmed, which was blocked by a CGRP antagonist while no difference was noticed in the innervated healthy control. We showed that sensory neurons can participate directly to keratinocyte hyperproliferation in the formation of psoriatic lesions through the release of CGRP, independently of the immune system. Our unique tissue-engineered innervated psoriatic skin model could be a valuable tool to better understand the mechanism by which nerves may modulate psoriatic lesion formation in humans. Statement of significanceThis study shows that keratinocytes extracted from patients’ psoriatic skin retain, at least in part, the disease phenotype. Indeed, when combined in a 3D model of tissue-engineered psoriatic skin, keratinocytes exhibited a higher proliferation rate, and produced a thicker epidermis than a healthy skin control. In addition, their hyperproliferation was aggravated by a treatment with CGRP, a neuropeptide released by sensory nerves. In a innervated model of tissue-engineered psoriatic skin, an increase in keratinocyte hyperproliferation was also observed after inducing neurons to release neuropeptides. This effect was prevented by concomitant treatment with an antagonist to CGRP. Thus, this study shows that sensory nerves can directly participate to affect keratinocyte hyperproliferation in psoriasis through CGRP release.

Identification of ADAM23 as a Potential Signature for Psoriasis Using Integrative Machine-Learning and Experimental Verification.

Psoriasis is a common chronic, recurrent, and inflammatory skin disease. Identifying novel and potential biomarkers is valuable in the treatment and diagnosis of psoriasis. The goal of this study was to identify novel key biomarkers of psoriasis and analyze the potential underlying mechanisms. Psoriasis-related datasets were downloaded from the Gene Expression Omnibus database to screen differential genes in the datasets. Functional and pathway enrichment analyses were performed on the differentially expressed genes (DEGs). Candidate biomarkers for psoriasis were identified from the GSE30999 and GSE6710 datasets using four machine learning algorithms, namely, random forest (RF), least absolute shrinkage and selection operator (LASSO) logistic regression, weighted gene co-expression network analysis (WGCNA), and support vector machine recursive feature elimination (SVM-RFE), and were validated using the GSE41662 dataset. Next, we used CIBERSORT and single-cell RNA analysis to explore the relationship between ADAM23 and immune cells. Finally, we validated the expression of the identified biomarkers expressions in human and mouse experiments. A total of 709 overlapping DEGs were identified, including 426 upregulated and 283 downregulated genes. Enhanced by enrichment analysis, the differentially expressed genes (DEGs) were spatially arranged in relation to immune cell involvement, immune-activating processes, and inflammatory signals. Based on the enrichment analysis, the DEGs were mapped to immune cell involvement, immune-activating processes, and inflammatory signals. Four machine learning strategies and single-cell RNA sequencing analysis showed that ADAM23, a disintegrin and metalloprotease, may be a unique, critical biomarker with high diagnostic accuracy for psoriasis. Based on CIBERSORT analysis, ADAM23 was found to be associated with a variety of immune cells, such as macrophages and mast cells, and it was upregulated in the macrophages of psoriatic lesions in patients and mice. ADAM23 may be a potential biomarker in the diagnosis of psoriasis and may contribute to the pathogenesis by regulating immunological activity in psoriatic lesions.

Effect of Narrow-Band Ultraviolet B Therapy of Psoriasis Vulgaris on Skin Directional Reflectance, Skin Density and Epidermal Thickness

Psoriasis is an inflammatory dermatosis manifested by the appearance of brown-red papules on the body, covered with silver scales. One of the most common and effective treatments for psoriasis is narrow-band UVB phototherapy. Narrow-band UVB has a wavelength of 311 nm, which results in shallow skin penetration, is absorbed only by the epidermis and the superficial layers of the dermis. The aim of the study was to assess the effect of narrow-band UVB 311 nm phototherapy on skin covered with psoriatic scales and without psoriatic lesions in patients with psoriasis vulgaris on the total directional hemispherical reflectance (DHR) of the skin, skin density and epidermis thickness. For this purpose, a 410 Solar DHR reflectometer and high-frequency ultrasonography DUB SkinScanner were used. A total of 48 volunteers were enrolled. There was a difference in the reflectance of skin without psoriatic scales and psoriatic skin. Depending on the wavelength range, the skin was characterized by different reflectance values. During the course of phototherapy, the reflectance values decreased, both in the psoriatic skin and skin without psoriatic scales. After the phototherapy, the epidermis thickness and SLEB layer decreased and skin density increased in the area with psoriatic plaque. The density of the skin without psoriasis after a series of 20 irradiations increased, while the thickness of the epidermis did not change.

Effects of liraglutide among patients living with psoriasis and obesity

Background and aimsThere is a bidirectional relationship between obesity and psoriasis. Liraglutide has been shown to improve the severity of psoriatic lesions in patients with type 2 diabetes. We aimed to study the effects of liraglutide 3mg in patients with obesity and psoriasis. MethodsTwenty patients started treatment with liraglutide 3mg for 3 months. Severity of the lesions was evaluated using the Psoriasis Area Severity Index (PASI) and the visual analogue scale of pain (VAS), and quality of life with the Dermatology Quality Index (DLQI). ResultsThere was a significant reduction in BMI (38.9±5.8 vs. 36.4±5.6; p<0.001), CRP (4.5±2.4 vs. 3±2mg/L; p<0.01), homocysteine (13.3±3.6 vs. 11.9±3μmol/L; p<0.01), ferritin (185.4±142.2 vs. 97.43±114.4ng/mL; p=0.04) and plasma cortisol (12±3.1 vs. 11.6±2.2μg/dL, p=0.04). PASI (10±8.4 vs. 5.1±6; p<0.0001), VAS (4.1±2 vs. 2.3±0.92; p=0.009) and DLQI (12.7±7 vs. 6.4±5.6, p<0.0001) improved significantly. In multiple regression analysis, weight loss did not correlate with any inflammatory parameter or PASI. ConclusionsLiraglutide 3mg for three months is effective and safe in reducing weight and improving psoriatic lesions among patients with psoriasis and obesity. Besides, there is an improvement in psoriatic lesions regardless of weight loss that deserves further studies.

Non-immune functions of inflammatory cytokines targeted by anti-psoriatic biologics: a review.

Psoriasis is an inflammatory disease characterized by skin thickening with silvery white desquamation due to dysregulated inflammatory pathways and elevated levels of inflammatory cytokines. Biologic agents targeting these inflammatory cytokines have brought about significant improvement in clearing psoriatic lesions in patients with moderate-to-severe psoriasis. Moreover, biologics exert both beneficial and detrimental effects on comorbidities in psoriasis, which include increased risk of cardiovascular events, metabolic syndrome, among other conditions. However, non-immune functions of cytokines targeted by biologics, and, hence, the potential risks and benefits of biologics for psoriasis to different organs/systems and comorbidities, have not been well elucidated. This review summarizes current understanding of the pathogenesis of psoriasis-related comorbidities and emerging discoveries of roles of cytokines targeted in psoriasis treatment, including tumor necrosis factor α and interleukins 12, 23, and 17, aiming to complete the safety profile of each biologics and provide therapeutic implications on psoriasis-related comorbidities, and on diseases involving other organs or systems.

Assessment of the Tissue Resident Memory Cells in Lesional Skin of Patients with Psoriasis and in Healthy Skin of Healthy Volunteers.

Background: In the course of plaque psoriasis, tissue resident memory cells (TRM) are responsible for the phenomenon of “immune memory” of lesions, i.e., the appearance of recurrences of lesions in the same location, as well as Koebner phenomenon. We present results determining the location and amount of TRM in psoriatic lesions in patients suffering from plaque psoriasis, as well as an analysis of the relationship between TRM markers expression and the duration and severity of the disease. Methods: TRM markers (CD4, CD8, CD103, CD69, CD49, CXCR6) and tissue expression of cytokines (IL-17, IL-22) in the lesional psoriatic skin of 32 patients compared with 10 healthy skin samples were evaluated by immunohistochemistry. Results: The presence of TRM markers in both the epidermis and skin with psoriatic eruptions was demonstrated in much higher amounts compared with the skin of healthy volunteers. A significant positive relationship was demonstrated between the expression of TRM markers in patients with plaque psoriasis and the duration of skin lesions. There was no relationship between the amount of TRM and the severity of plaque psoriasis. Conclusions: A thorough understanding of the mechanisms responsible for the development and relapse of plaque psoriasis may contribute to the implementation of more effective therapies.

Persistent expression of interleukin-17 and downstream effector cytokines in recalcitrant psoriatic lesions after ustekinumab treatment.

The interleukin (IL)-23/T-helper (Th)17 axis is considered central to the pathogenesis of psoriasis, with IL-36γ considered a marker for histological differential diagnosis. However, expression data regarding key cytokines in the pathogenesis of psoriasis, as well as data on the effects of IL-23 inhibition on downstream cytokines in human psoriatic skin, are limited. We investigated the expression profile of key cytokines and the effect of ustekinumab (UST) on cytokine expression in human psoriatic tissue. Tumor necrosis factor (TNF)-α, IL-23, IL-17A, and IL-22 were highly expressed in the epidermis, dermal papillae, and upper dermis in patients with psoriasis compared with controls; IL-36γ was strongly expressed in the upper epidermis. Compared with the untreated group, expression intensity and area of IL-23 were significantly decreased in the UST group; expression areas of TNF-α, IL-17A, IL-22, and IL-36γ did not differ. This study identified the distribution and quantitative expression levels of key cytokines in psoriatic lesions and demonstrated that only IL-23 was downregulated without blocking downstream effector cytokines in recalcitrant psoriatic lesions during UST treatment. Our results suggest that, although IL-23 is inhibited, the persistent expression of IL-17 through an alternative pathway maintains the vicious cycle of the TNF-α/IL-23/IL-17 axis with IL-36γ, inducing refractory psoriatic lesions in patients with well-controlled psoriasis.

Oral health status of psoriatic patients managed with modern biological therapy.

Psoriasis is a chronic multifactorial dermatosis with an autoimmune and genetic background, with characteristic periods of remission and exacerbation, affecting up to 3% of the population; it is currently regarded as a systemic disease. To investigate the oral health status, including oral mucosal lesion frequency and prosthetic treatment requirements, in psoriatic patients managed with biological therapies. Forty-two patients diagnosed with psoriasis and managed with biologics were enrolled in this study. All subjects completed a general medical history and a Dermatology Life Quality Index (DLQI) questionnaire. The disease severity was assessed using the Psoriasis Area and Severity Index (PASI) scale and a DLQI questionnaire. To evaluate the oral health status, the following techniques were used: Approximal Plaque Index (API), the Community Periodontal Index (CPI), and the Decayed, Missing, and Filled Teeth (DMFT) index. The oral mucosa evaluation was based on the clinical appearance, location, and morphology of the lesions. The most common oral lesions in patients with psoriasis were found to be fissured tongue and white coated tongue. Thirteen patients (31%) presented with clinically healthy oral mucosa. Type II (diffuse type) denture stomatitis (DS) was most common amongst psoriatic patients wearing acrylic removable dentures. Most of the subjects required prosthetic treatment (57.1 %) and the removal of calculus (40.5%); however, no one required surgical treatment. Fissured tongue seemed to be associated with skin lesions in psoriatic patients managed with biological therapies. The need for dental treatment was observed in 71.4% of the patients, with most subjects requiring prosthetic treatment. The study indicated that the diffuse type of DS occurred amongst subjects with psoriasis, who were wearers of acrylic removable dentures.

Oral mucosal lesions in psoriatic patients based on disease severity and treatment approach.

This observational case-control study was designed to investigate the frequency of oral lesions in psoriatic patients and to identify an association between mucosal involvement, the severity of the disease, and a form of treatment. One hundred twenty-seven patients diagnosed with psoriasis were enrolled in this study from November 2018 to September 2019. The oral mucosa evaluation was based on the clinical appearance, location, and morphology of the lesions. All patients completed a general medical history and a Dermatology Life Quality Index (DLQI) questionnaire. The severity of skin involvement was assessed using the Psoriasis Area and Severity Index (PASI) scale. The most common oral lesions in patients with psoriasis were found to be fissured (FT), white coated (CT), and geographic tongue (GT). A significantly lower prevalence of GT was evident in the group managed with a new class of biological drugs and smokers. There appeared to be no association between the oral manifestation and the PASI score. FT appeared significantly more often in patients that experienced an extremely large effect of psoriasis on their quality of life as determined by the DLQI questionnaire and smokers. Only 25% of patients presented normal oral mucosa. Tongue lesions seem to be associated with skin psoriasis regardless of the treatment. The severity of the disease, according to the PASI scale, does not influence mucosal involvement. The type of treatment may affect the prevalence of oral lesions. Further investigations are required to confirm the influence of biological therapies on mucosal improvement.

P273 Ustekinumab and guselkumab treatment results in differences in serum IL-17A, IL-17F and CRP levels in PsA patients: a comparison from ustekinumab Phase 3 and guselkumab Phase 2 programmes

Abstract Background Ustekinumab (UST) is a monoclonal antibody (mAb) that binds the p40 epitope which is shared by IL-12 and IL-23, whereas guselkumab (GUS) is a mAb that selectively binds the p19 subunit of IL-23. In recent studies, both UST (Phase 3 programs) and GUS (Phase 2 program) have demonstrated a reduction in musculoskeletal clinical signs and symptoms and improvement of psoriatic lesions in patients with active psoriatic arthritis (PsA), implicating the IL-12/23 pathway in disease pathogenesis. This analysis explored the post-treatment pharmacodynamic changes of IL-17A, IL-17F, and CRP with GUS and UST in the context of PsA. Methods Serum protein levels of IL-17A, IL-17F, and CRP were measured in 142 subjects and 38 matched healthy controls from the GUS Phase 2 study at Week (W)0, W4, and W16. In the UST Phase 3 studies, biomarkers were assayed at W0, W4, and W24 as follows: IL-17A (n = 474), IL-17F (n = 237), CRP (n = 927). IL-17A and IL-17F were assayed using Single Molecule CountingTM Human Immunoassay Kits (formerly Singulex). CRP was measured using CardioPhase hsCRP assay (UST studies) or Meso Scale Discovery Platform (GUS study). Results At baseline, the Th17 effector cytokines IL-17A and IL-17F were elevated in the serum of PsA subjects in the GUS Phase 2 cohort compared to healthy controls. IL-17A and IL-17F levels significantly correlated with affected skin body surface area, but not swollen or tender joint scores, in both studies. While none of the baseline levels of evaluated cytokines were associated with American College of Rheumatology (ACR) or Psoriasis Area Severity Index (PASI) clinical responses to UST, baseline IL-17F levels were modestly associated with ACR20 response to GUS at Week 24. Both UST and GUS treatment resulted in pharmacodynamic decreases in IL-17A, IL-17F, and CRP levels, with GUS treatment restoring IL-17A and IL-17F levels to that of healthy controls by W16. Consistent with being a component of ACR scores, CRP changes were significantly associated with ACR20 responses to both UST and GUS treatment. W4 and W16 changes in IL-17F with GUS treatment were significantly associated with ACR20 response at W24. W24 PASI75 response to GUS was significantly associated with W4 changes in IL-17A, with a similar trend observed at W16. Conclusion These results underscore the relevance of the IL-23/Th17 pathway in PsA, with GUS treatment providing a stronger suppression of the pathway than UST treatment. The significant associations of changes in IL-17A and IL-17F levels with GUS treatment with PASI75 and ACR20 response, respectively, support the importance of the IL-23/Th17 pathway for both skin and joint pathologies. The associations of reduction in CRP levels with both UST and GUS treatment also reinforce the role of acute phase inflammation in joint pathology. Disclosures S. Siebert: Other; S.S. has been a study investigator for Janssen. M.J. Loza: Other; M.L. is a Janssen employee. Q. Song: Other; Q.S. is a Janssen employee. P.C. Gorecki: Other; P.G. is a Janssen employee. I.B. McInnes: Other; I.M. has been a study investigator for Janssen. K. Sweet: Other; K.S. is a Janssen employee.

Efficacy of Adding Oral Simvastatin to Topical Therapy for Treatment of Psoriasis: The Vietnamese Experience.

BACKGROUND:Psoriasis, the prevalence of which ranges from 2% to 3% of the general population, has been recently recognised as not only a chronic inflammatory skin disorder but also an immunometabolic systemic disease. Dyslipidemia is one of the most important comorbidities of psoriasis. Statins, frequently used as anti-hyperlipidemic agents, may be beneficial in the treatment of several autoimmune diseases, including psoriasis, due to their anti-inflammatory and immunomodulatory characteristics. Hence, we hypothesised that using this medication was not only beneficial for reducing hyperlipidemia but also improving psoriatic conditions.AIM:We conducted a study to determine the prevalence of dyslipidemia in psoriatic patients as well as whether the addition of statins (simvastatin prescribed forms) to standard topical antipsoriatic treatment can improve skin lesions in psoriatic patients.METHODS:A group of 128 psoriatic patients and 128 healthy controls who were matched with the patients regarding ethnicity, age, and sex were enrolled, and their lipid concentrations were determined. Furthermore, sixty patients were randomly selected from the former group and divided into two treatment subgroups to evaluate the effect of statins on the severity of psoriasis using the PASI score.RESULTS:We found that the rate of dyslipidemia in the patient group was significantly higher than in the healthy group (53.9% versus 21.9%, p < 0.001), particularly the triglyceride concentration (1.86 ± 1.17 versus 1.43 ± 0.79 mg/dL, p < 0.001). Also, the PASI score reduction in the simvastatin-treated subgroup was significantly different from that in the placebo-treated one after eight weeks of therapy (8.63 ± 4.78 versus 5.34 ± 3.59, p < 0.01).CONCLUSION:This study showed that simvastatin might play a role in controlling hyperlipidemia and in turn decrease the PASI score in psoriatic patients.

Transepidermal Water Loss in Psoriasis: A Case-control Study.

Context:Psoriasis is a common papulosquamous disorder characterized by increased epidermal turnover resulting in excessive skin shedding and a compromised barrier function of the skin. Transepidermal water loss (TEWL) is an effective and non-invasive way to measure the barrier function in this condition.Aims:To measure the physiological changes in the skin barrier function in psoriasis by measuring the extent of TEWL. To study the differences in TEWL in pathologically involved and uninvolved skin in psoriasis. To compare the TEWL in skin lesions in psoriatic patients and site matched controls.Subjects and Methods:To determine the barrier quality of the stratum corneum, we performed TEWL measurements using the closed chamber evaporation method (VapoMeter Delfin Technologies, Kuopio, Finland). The ambient temperature ranged between 21°C and 24°C, with a mean relative humidity range of 39%–50%. In total, four sites were measured for all the 50 cases, two involved plaques on the body were selected for the study of lesional psoriatic skin, and the standard sites of ankle and elbow were measured irrespective of being involved or uninvolved with psoriatic skin. TEWL measurements in controls were site matched. Statistical testing was done using SPSS ver. 17. The interval scale data were tested for normality using Shapiro-Wilk test, and between groups testing was done using Mann-Whitney test.Results:The TEWL was higher among the cases in all the four measured areas compared to the controls, thus showing overall impaired skin barrier function in psoriatic skin. In addition, among the cases, the involved sites show higher TEWL in comparison to the uninvolved skin. This is highly suggestive that plaques of psoriasis have reduced water holding capacity.Conclusions:Psoriasis is a dermatosis with overall compromise of the skin barrier function exhibiting exponential TEWL in lesional skin, with increased TEWL over non-lesional skin as well. Thus, it may be concluded that TEWL is an effective, non-invasive and objective method in assessment of skin barrier function.

Application of Photoacoustic Methods and Confocal Microscopy for Monitoring of Therapeutic Response in Plaque Psoriasis

Psoriasis is prone to relapses and requires long-term therapy that may induce a range of adverse effects; therefore, an efficient and early detection of relapses is desirable. In this study, photoacoustic imaging and confocal laser scanning microscopic (CLSM) methods were investigated for their suitability in psoriasis follow-up examinations. Using a high-resolution photoacoustic system, the vascular structures of 11 psoriatic patients and 6 healthy volunteers were investigated. No differences were detected with respect to the average vessel diameter and vasculature per unit volume in the tissue of healthy volunteers and non-lesional and lesional skin areas of psoriatic patients. By means of CLSM, the diameters of the dermal papillae of 6 volunteers and 6 psoriatic patients were determined. The diameters of the dermal papillae of the healthy volunteers (0.074 ± 0.006 mm) revealed no significant difference when compared to non-lesional skin areas of psoriatic patients (0.079 ± 0.005 mm). The results obtained for the lesions in psoriatic patients showed a significant difference (Wilcoxon test, p = 0.028) between the diameters of the dermal papillae of the lesional skin areas (0.114 ± 0.012 mm) and the non-lesional skin areas (0.079 ± 0.005 mm). Thus, CLSM can be applied for monitoring psoriasis follow-up examinations.

Possible role of proenkephalin in psoriasis.

Psoriasis is a common chronic skin disease that can also affect the mucous membranes and joints. It is multifactorial in origin, occurring in genetically predisposed individuals, and triggered by various endogenous and exogenous factors. Proenkephalin (PENK) is an endogenous opioid polypeptide hormone that acts on specific opiate receptors found on nerve and mucosal cells, and on various cells in the immune system. PENK receptors are expressed on skin cells, and their activation can regulate keratinocyte and melanocyte activities. PENK expression has been found to be increased in keratinocytes in psoriatic skin, and together with its inflammatory basis, this suggests that PENK may be regulated by inflammatory stimuli. To assess the possible role of PENK in the pathogenesis of psoriasis and to assess if it is related to the severity of psoriatic lesions. Serum and tissue PENK levels were estimated in 20 patients with psoriasis vulgaris, and compared with those of 20 healthy controls (HCs). PENK levels were found to be significantly increased both in serum and in psoriatic lesions in patients compared with HCs. No significant correlation was found between PENK levels and patient age, disease duration or disease severity (Psoriasis Area and Severity Index). Our results support the role of PENK in the aetiopathogenesis of psoriasis, and indicate that giving anti-PENK drugs in addition to current antipsoriatic therapies might be of value in treating this common chronic skin disease.

Prevalence of oral mucosal lesions in psoriatic patients: A controlled study

Objectives: This study aimed to investigate and compare the prevalence of oral mucosal lesions in a group of psoriatic patients and healthy subjects, and its correlation to multiple clinical parameters. Study design: 100 psoriatic patients and 100 closely matched controls underwent clinical oral examination. Oral lesions were diagnosed according to the criteria proposed by the World Health Organization (WHO). The patients filled the Hospital Anxiety and Depression (HAD) questionnaire and the Dermatology Life Quality Index (DLQI). The severity of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI). Categorical variables were evaluated using Chi-square test or Fisher’s exact test with overall significance set at p< 0.05. Results: Oral mucosal lesions were diagnosed in 43 (43%) psoriatic patients and 17 (17%) control subjects (p=0.000). Comparing psoriatic patients to control subjects the prevalence of fissured tongue (FT) was 35% vs. 13% (p=0.000); geographic tongue (GT) 17% vs. 9% (p=0.09); combination of FT and GT 5% vs. 5% (p=1.00); oral candidosis 3% vs. 0% (p=0.81); leukoedema 1% vs. 3% (p=0.62); physiologic melanin pigmentations 4% vs. 1% (p=0.37) respectively. The clinical type of psoriasis, duration of the disease, method of disease management (medicated vs. non-medicated for psoriasis), smoking habit, psychological status or the disease severity did not influence the prevalence of FT and GT. Psoriatic patients who experienced “very large” to “extremely large” adverse effect of psoriasis on their quality of life have significantly higher prevalence of GT (p=0.04). Conclusions: FT is significantly more common in psoriatic patients compared to controls; hence studies investigating the nature of this relationship are warranted. Oral health care providers should be aware of the predisposition of psoriatic patients to oral candidosis. Key words:Oral lesions, fissured tongue, geographic tongue, leukoedema, oral Candida, candidosis, psoriasis.

A mathematical model of paracrine regulation of the proliferative activity of epidermis with the participation of T lymphocytes

A mathematical model of paracrine regulation of the proliferative activity of epidermis in the foci of skin lesions in psoriatic patients is presented. The model simulates the participation of skin-infiltrating activated T-lymphocytes as cellular regulators of apoptosis of proliferating keratinocytes. It allows one to describe all basic phases of the development of the focus of psoriatic lesion: the beginning of formation, a long stable or periodic manifestation, and the resolution of lesion and its involution to clinically uninvolved and normal skin. The model shows also the possibility of a spasmodic (triggering) transition of a pathological focus of lesion from the condition of remission to a new exacerbation and vice versa, which is a characteristic feature of the disease.

Contact immunotherapy-induced Renbök phenomenon in a patient with alopecia areata and psoriasis vulgaris

Auteur(s) : Taisuke Ito, Hideo Hashizume, Masahiro Takigawa Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 Japan Happle et al. first introduced the term “Renbok phenomenon”, derived from the reversal of “Kobner”, to describe the observation of normal hair growth in psoriatic lesions in patients with co-existing psoriasis and alopecia areata (AA) [1]. Although the exact mechanism [...]

Treatment with 311-nm ultraviolet B accelerates and improves the clearance of psoriatic lesions in patients treated with etanercept

Some patients with plaque-type psoriasis respond slowly to treatment with etanercept. In such cases combining etanercept with conventional treatments might be helpful. To investigate whether treatment with 311-nm ultraviolet (UV) B can improve the therapeutic response in patients treated with etanercept. Four women and one man (mean age 57 years, range 48-66) with moderate to severe plaque-type psoriasis who had received standard treatment with etanercept 50 mg twice weekly for 6 weeks without Psoriasis Area and Severity Index (PASI) reduction of 75% or greater (of initial mean PASI of 16.0, range 15.4-20.4) were enrolled in the study. Starting at 6 weeks, 311-nm UVB treatment was given to a randomly selected body half (left or right, excluding the head) for another 6 weeks, while all patients continued receiving etanercept. The patients were monitored by half-body PASI at weekly intervals. During the 6-week irradiation regimen, 311-nm UVB significantly bolstered the therapeutic response in the patients on etanercept treatment. After 6 weeks of 311-nm UVB, the patients had a mean PASI on their UV-irradiated body halves of 1.6 (range 0.6-3.3) vs. 4.7 (range 1.4-8.6) on nonirradiated body halves (P = 0.0192, paired two-tailed t-test), compared with 10.7 (range 6-16.4) and 10.5 (range 5.2-16.4) at start of 311-nm UVB treatment. The overall mean PASI reduction from baseline (i.e. at etanercept start) was 89% vs. 68%, respectively (P = 0.0009 and P = 0.0088). Treatment with 311-nm UVB significantly accelerates and improves the clearance of psoriatic lesions in patients responding slowly to etanercept monotherapy.

The Effect of Pioglitazone on Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, Tumor Necrosis Factor-α, Vascular Endothelial Growth Factor and E-Selectin in Skin Lesions in Psoriatic Patients with and without Psoriatic Arthritis

Psoriasis is a common inflammatory skin disease characterized by infiltration of inflammatory cells into the epidermis and altered keratinocyte differentiation. The aim of the present study was to investigate the role of MMP-9 in the development of psoriasis by assessing the presence of MMP-9 in lesional skin and in sera of psoriatic patients with & without psoriatic arthritis, the association of MMP-9 with the activity of the disease, the relationship between MMP-9 and TNF-

The Effect of Pioglitazone on Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, Tumor Necrosis Factor-α, Vascular Endothelial Growth Factor and E-Selectin in Skin Lesions in Psoriatic Patients with and without Psoriatic Arthritis

Background: Psoriasis is a common inflammatory skin disease characterized by infiltration of inflammatory cells into the epidermis and altered keratinocyte differentiation. The aim of the present study was to investigate the role of MMP-9 in the development of psoriasis by assessing the presence of MMP-9 in lesional skin and in sera of psoriatic patients with & without psoriatic arthritis, the association of MMP-9 with the activity of the disease, the relationship between MMP-9 and TNF-α production as well as to evaluate the effect of pioglitazone (one of the agents thiazolidinediones) on TNF-α, MMP-9, MMP-2, VEGF and E- selectin production and in treatment of psoriasis. Subjects and Methods: Thirty-five psoriatic patients (28 males, 7 females) were included in this study. They were divided into 2 groups. Group I (PsA) included 15 psoriatic patients, clinically presenting joint symptoms associated to the cutaneous disease (PsA). Group II (Ps) included 20 psoriatic patients, clinically presenting cutaneous disease without psoriatic arthritis (PsA). Each psoriatic patient received pioglitazone 30 mg/day orally for 10 weeks. Lesional tissue specimens were taken, in the same skin area before and after 10 weeks pioglitazone treatment. Tissues were kept in short term cultures and production soluble mediators such as TNF-α, MMP-9, MMP-2, VEGF and E-selectin, which include angiogenic molecules associated to the development of plaque psoriasis, were measured in the culture supernatants by ELISA. MMP-9 concentrations were also measured in the sera. The cutaneous activity of disease was evaluated by the Psoriasis Area and Severity Index (PASI). Results: Clinical and laboratory assessment indicated that all patients had a significant improvement of the PASI score after 10 weeks of pioglitazone therapy. The clinical improvement was associated to a significant decrease of TNF-α, MMP-9, MMP-2, VEGF& E- selectin levels (P< 0.05) , spontaneously released by lesional biopsies before and after therapy. A significant decrease of MMP-9 (P< 0.01) in the sera, associated to the clinical improvement was also found. In addition, significant positive correlations (P< 0.01) were found between the TNF-α and PASI score, MMP-9, MMP-2, VEGF& E-selectin (r=0.85, 0.84, 0.58, 0.63, 0.67 respectively), as well as between the MMP-9 and PASI, MMP-2, VEGF& E-selectin (r=0.82, 0.39, 0.69, 0.41 respectively) of patients with PsA after pioglitazone treatment. In psoriatic patients without psoriatic arthritis after pioglitazone treatment there were also significant positive correlations between the TNF-α and PASI score ,MMP-9, MMP-2, VEGF& E- selectin(r=.0.87, 0.68, 0.53, 0.61, 0.51 respectively), as well as between MMP-9 and PASI, MMP-2, VEGF& E-selectin (r=0.95, 0.51, 0.58, 0.45 respectively). Conclusion: The current study shows the existence of a direct relationship between MMP- 9 and TNF-α production strongly suggesting that MMP-9 may play a key role in the skin inflammatory process. Our findings also demonstrated that pioglitazone could be considered as an efficacious and safe agent for the treatment of psoriasis. The optimum dose and duration of pioglitazone therapy remain to be determined.