Psoriasis Lesions Research Articles

Separation, characterization and anti-psoriasis effect of self-assembled nanoparticles from Shaoyao Gancao Decoction

This study aims to separate and characterize self-assembled nanoparticles(SAN) from Shaoyao Gancao Decoction(SGD) and determine the content of active compounds. Further, we aimed to observe the therapeutic effect of SGD-SAN on imiquimod-induced psoriasis in mice. The separation of SGD was performed by dialysis, and the separation process was optimized by single factor experiment. The SGD-SAN isolated under the optimal process was characterized, and the content of gallic acid, albiflorin, paeoniflorin, liquiritin, isoliquiritin apioside, isoliquiritin, and glycyrrhizic acid in each part of SGD was determined by HPLC. In the animal experiment, mice were assigned into a normal group, a model group, a methotrexate group(0.001 g·kg~(-1)), and SGD, SGD sediment, SGD dialysate, and SGD-SAN groups of different doses(1, 2, and 4 g·kg~(-1)) respectively. The psoriasis grade of mice was evaluated based on the pathological changes of skin lesions, the content of inflammatory cytokines, organ index and other indicators. The results showed that SAN obtained by centrifugation at 13 000 r·min~(-1) for 30 min was stable after dialysis for 4 times, which were uniform spherical nanoparticles with the particle size of(164.43±1.34) nm, the polydispersity index of(0.28±0.05), and the Zeta potential of(-12.35±0.80) mV. The active compound content accounted for more than 70% of SGD. Compared with the model group, SAN and SGD decreased the skin lesion score, spleen index, and inflammatory cytokine levels(P<0.05 or P<0.01) and alleviated the skin thickening and infiltration of inflammatory cells. However, the sediment group and the dialysate group had no obvious effect. SGD showed a good therapeutic effect on imiquimod-induced psoriasis in mice, and SAN demonstrated the effect equivalent to SGD in a dose-dependent manner. Therefore, we conclude that the SAN formed during decocting is the main active form of SGD, which can lower the levels of inflammatory cytokines, promote the normal differentiation of keratinocytes, and reduce the infiltration of inflammatory cells in the treatment of psoriasis lesions in mice.

Vitamin D Receptor Expression in Chronic Plaque Psoriasis Before and After Narrowband Ultraviolet B Phototherapy.

Psoriasis is a multifactorial disease. It is a combination of genetic, immunological, and environmental factors. Vitamin D receptor (VDR) is a nuclear receptor that regulates epidermal cell growth through the inhibition of proliferation and induction of keratinocytes terminal differentiation. Aim of the study was to investigate the effect of Narrow-band UVB (NB-UVB) therapy on VDR expression in the skin of psoriasis patients. Forty patients with different severities of psoriasis were assessed using the psoriasis area and severity index (PASI) score. Lesional and non-lesional skin biopsies were obtained from each patient before NB-UVB therapy, and then a third lesional biopsy was performed after completing 24 sessions of NB-UVB. Immunohistochemistry for VDR was performed on all specimens. There was a significant decrease in VDR expression in psoriatic lesions compared to that in non-lesional skin before treatment. A statistically negative correlation was detected between the degree of VDR expression before treatment and PASI score, family history, and duration of psoriasis. There was a significant increase in VDR expression at the sites of psoriasis lesions post-NB-UVB therapy compared to pretreatment lesional skin. VDR expression was down-regulated in psoriatic lesions compared to non-lesional skin, and NB-UVB therapy improved VDR expression in psoriasis skin lesions.

IL17A Blockade with Ixekizumab Suppresses MuvB Signaling in Clinical Psoriasis

Unbiased informatics approaches have the potential to generate insights into uncharacterized signaling pathways in human disease. In this study, we generated longitudinal transcriptomic profiles of plaque psoriasis lesions from patients enrolled in a clinical trial of the anti-IL17A antibody ixekizumab (IXE). This dataset was then computed against a curated matrix of over 700 million data points derived from published psoriasis and signaling node perturbation transcriptomic and chromatin immunoprecipitation-sequencing datasets. We observed substantive enrichment within both psoriasis-induced and IXE-repressed gene sets of transcriptional targets of members of the MuvB complex, a master regulator of the mitotic cell cycle. These gene sets were similarly enriched for pathways involved in the regulation of the G2/M transition of the cell cycle. Moreover, transcriptional targets for MuvB nodes were strongly enriched within IXE-repressed genes whose expression levels correlated strongly with the extent and severity of the psoriatic disease. In models of human keratinocyte proliferation, genes encoding MuvB nodes were transcriptionally repressed by IXE, and depletion of MuvB nodes reduced cell proliferation. Finally, we made the expression and regulatory networks that supported this study available as a freely accessible, cloud-based hypothesis generation platform. Our study positions inhibition of MuvB signaling as an important determinant of the therapeutic impact of IXE in psoriasis.

Downregulation of circ_0024028 inhibits IL-22-induced keratinocyte proliferation and migration by miR-486-3p/AKT3 axis.

Circular RNA (circRNA) has been confirmed to participate in psoriasis process, but the role of circ_0024028 in psoriasis development is still unclear. Interleukin 22 (IL-22)-induced keratinocytes (HaCaT) were used to construct psoriasis cell models in vitro. The expression of circ_0024028, microRNA (miR)-486-3p and AKT serine/threonine kinase 3 (AKT3) was analyzed by quantitative real-time PCR. Cell function was assessed by cell counting kit 8 assay, EdU assay, transwell assay, and wound healing assay. Protein expression was examined using western blot analysis. RNA interaction was confirmed by dual-luciferase reporter assay and RIP assay. Exosomes were isolated from cell culture medium using ultracentrifugation and examined by transmission electron microscopy and nanoparticle tracking analysis. Circ_0024028 was highly expressed in psoriasis lesions and IL-22-induced HaCaT cells, and its silencing could inhibit IL-22-induced HaCaT cell proliferation and migration. MiR-486-3p could be sponged by circ_0024028, and its inhibitor restored the functions of circ_0024028 knockdown on IL-22-induced HaCaT cell proliferation and migration. AKT3 was targeted by miR-486-3p, and its overexpression reversed the inhibitory effect of miR-486-3p on IL-22-induced HaCaT cell proliferation and migration. AKT3 expression was positively regulated by circ_0024028, and circ_0024028/miR-486-3p/AKT3 axis could regulate the activity of AKT/mTOR pathway. Additionally, exosomes mediated the transfer of circ_0024028 in cells. Circ_0024028 might be a potential target for psoriasis treatment, which knockdown repressed IL-22-induced keratinocytes proliferation and migration through miR-486-3p/AKT3 pathway.

Supramolecular Dissolving Microneedle Patch Loading Hydrophobic Glucocorticoid for Effective Psoriasis Treatment.

Glucocorticoid-based creams are commonly used for treatments of psoriatic skin lesions while showing poor permeation because the thickened stratum corneum severely limits drug absorption. Although dissolving microneedle (DMN) patches have been employed in treating skin disease by virtue of their direct target to the lesion site, conventional DMN patches are generally fabricated from the water-soluble matrix, making them difficult to efficiently encapsulate hydrophobic glucocorticoids. Here, we develop a mechanically robust supramolecular DMN composed of hydroxypropyl β-cyclodextrin (HPCD) to effectively and uniformly load triamcinolone acetonide (TA). The TA-loaded HPCD DMN (TAMN) exhibits excellent mechanical performance that can easily pierce the thickened psoriasis lesions and deliver TA efficiently. Owing to the increased water solubility and bioavailability of TA after inclusion into HPCD, TAMN shows a superior in vitro inhibitory effect on immortalized human keratinocyte (HaCaT) cells. Importantly, the administration of TAMN twice a week effectively alleviates psoriatic signs and reduces the expression of Ki67, IL-23, and IL-17 in the ear lesions of imiquimod-induced psoriasis-like mice. This supramolecular DMN provides a promising strategy for the efficient treatment of psoriasis and other skin diseases, greatly broadens the applications of supramolecular materials in transdermal drug delivery, and widens the range of drugs in DMNs.

Durability of Efficacy and Safety of Roflumilast Cream 0.3% in Adults With Chronic Plaque Psoriasis From a 52-Week, Phase 2 Open-Label Safety Trial

Background: Roflumilast cream is a potent phosphodiesterase 4 inhibitor recently approved in the United States for treatment of plaque psoriasis with no limitations on duration of use. An open-label trial was conducted to evaluate long-term safety (52 weeks) of once-daily roflumilast cream (NCT03764475). This abstract presents data on durability of response as measured by the percentage of patients with an Investigator Global Assessment (IGA) score of Clear or Almost Clear, percentage improvement in Psoriasis Area Severity Index (PASI) score, and reduction in body surface area (BSA) affected. Methods: Patients who completed a parent, phase 2b, 12-week randomized controlled trial could continue on open-label roflumilast cream 0.3% (Cohort-1, n=230), and patients naïve to roflumilast were also enrolled (Cohort-2, n=102). All psoriasis lesions (except scalp) were treated, including face and intertriginous areas for up to 52 weeks. If affected, palms and soles were treated, but not evaluated towards any efficacy assessments. Median duration of response was determined using the Kaplan-Meier method. Results: With cumulative treatment up to 64 weeks in Cohort-1 and 52 weeks in Cohort-2, long-term safety and tolerability were consistent with the 12-week, phase 2b study. Overall, 73.5% of patients completed the study; 3.9% discontinued due to adverse events (AE) and 0.9% discontinued due to lack of efficacy. Treatment-related AEs were reported in 2.7% patients; none were deemed serious. Investigator tolerability assessments at each visit demonstrated 99% of patients rated “no evidence of irritation.” At Week 52, IGA Success (demonstrating Clear/Almost Clear plus 2-grade improvement from baseline) was achieved by 34.8% of patients in Cohort-1 and 39.5% in Cohort-2. Of patients in Cohort-2, 40% of patients achieved IGA success at week 12. IGA Clear/Almost Clear was achieved by 46.8% of patients across both cohorts at week 12 and consistent through week 52 (44.8%). Similarly, a 60.5% mean PASI improvement and 60.1% mean BSA improvement from baseline were observed at week 12 and consistent through week 52 (59.4% and 63.3%, respectively). Of the 185 patients who achieved IGA Clear/Almost Clear during the open-label trial, the median durability of IGA of Clear/Almost Clear was 10 months (40.1 weeks). Among patients who achieved an IGA of Clear or Almost Clear, 50% maintained Clear or Almost Clear status for at least 10 months. Conclusions: In this long-term safety study, roflumilast cream was well tolerated with a safety profile consistent with the parent Ph2b trial, and effectively maintained clear/almost clear skin with no tachyphylaxis observed. Sponsored by Arcutis Biotherapeutics, Inc.

IMAGE SEGMENTATION WITH A CONVOLUTIONAL NEURAL NETWORK WITHOUT POOLING LAYERS IN DERMATOLOGICAL DISEASE DIAGNOSTICS SYSTEMS

Context. The problem of automating of the segmentation of spectral-statistical texture images is considered. The object of research is image processing in dermatological disease diagnostic systems.
 Objective. The aim of the research is to improve the segmentation performance of color images of psoriasis lesions by elaboration of a deep learning convolutional neural network without pooling layers.
 Method. The convolutional neural network is proposed to process a three-channel psoriasis image with a specified size. The initial color images were scaled to the specified size and then inputed on the neural network. The architecture of the proposed neural network consists of four convolutional layers with batch normalization layers and ReLU activation function. Feature maps from the output of these layers were inputted to the 1*1 convolutional layer with the Softmax activation function. The resulting feature maps were inputted to the image pixel classification layer. When segmenting images, convolutional and pooling layers extract the features of image fragments, and fully connected layers classify the resulting feature vectors, forming a partition of the image into homogeneous segments. The segmentation features are evaluated as a result of network training using ground-truth images which segmented by an expert. Such features are robust to noise and distortion in images. The combination of segmentation results at different scales is determined by the network architecture. Pooling layers were not included in the architecture of the proposed convolutional neural network since they reduce the size of feature maps compared to the size of the original image and can decrease the segmentation performance of small psoriasis lesions and psoriasis lesions of complex shape.
 Results. The proposed convolutional neural network has been implemented in software and researched for solving the problem of psoriasis images segmentation.
 Conclusions. The use of the proposed convolutional neural network made it possible to enhance the segmentation performance of plaque and guttate psoriasis images, especially at the edges of the lesions. Prospects for further research are to study the performance of the proposed CNN then abrupt changes in color and illumination, blurring, as well as the complex background areas are present on dermatological images, for example, containing clothes or fragments of the interior. It is advisable to use the proposed CNN in other problems of color image processing to segment statistical or spectral-statistical texture regions on a uniform or textured background.

IRAK4 inhibition dampens pathogenic processes driving inflammatory skin diseases.

Innate immunity not only shapes the way epithelial barriers interpret environmental cues but also drives adaptive responses. Therefore, modulators of innate immune responses are expected to have high therapeutic potential across immune-mediated inflammatory diseases. IRAK4 is a kinase that integrates signaling downstream of receptors acting at the interface between innate and adaptive immune responses, such as Toll-like receptors (TLRs), interleukin-1R (IL-1R), and IL-18R. Because effects of IRAK4 inhibition are stimulus, cell type, and species dependent, the evaluation of the therapeutic potential of IRAK4 inhibitors requires a highly translational approach. Here, we profiled a selective IRAK4 inhibitor, GLPG2534, in an extensive panel of models of inflammatory skin diseases, translationally expanding evidence from in vitro to in vivo and from mouse to human. In vitro, IRAK4 inhibition resulted in substantial inhibition of TLR and IL-1 responses in dendritic cells, keratinocytes, granulocytes, and T cells but only weakly affected dermal fibroblast responses. Furthermore, disease activity in murine models of skin inflammation (IL-23-, IL-33-, imiquimod-, and MC903-induced) was markedly dampened by IRAK4 inhibition. Last, inhibiting IRAK4 reversed pathogenic molecular signatures in human lesional psoriasis and atopic dermatitis biopsies. Over the variety of models used, IRAK4 inhibition consistently affected central mediators of psoriasis (IL-17A) and atopic dermatitis (IL-4 and IL-13). Overall, our data highlight IRAK4 as a central player in skin inflammatory processes and demonstrate the potential of IRAK4 inhibition as a therapeutic strategy in chronic inflammatory skin diseases.

Inverse psoriasis: the diagnostic value of dermatoscopic assessment and the experience of treatment with a combination topical agent (a clinical series)

Background: Inverse psoriasis that is characterized by skinfold rash is seen in 12 to 36% of European patients with psoriasis. Isolated involvement of skinfolds can mimic a number of dermatoses with similar location. The differential diagnosis is increasingly frequently based on non-invasive methods, including dermatoscopy. Taking into account the warm and wet milieu of skinfolds, facilitating secondary infection, topical antibacterials and antiseptics are recommended for treatment, along with topical glucocorticosteroids and vitamin D3 analogues.
 Materials and methods: We have analyzed the results of assessment and treatment of 15 patients with psoriasis of major skinfolds that were admitted to the in-patient department of dermatology. All patients underwent dermatoscopy at 20 magnification. The patients were treated with desensitizing agents, hepatic protectors, and group B vitamins. Topical treatments applied in the rash areas included a combination topical agent containing mometasone furoate (0.5 mg), gentamicin sulfate (1 mg), econazole nitrate (10 mg), and dexpanthenol (50 mg). The treatment was considered effective if the M-PASI decreased at least by 75%; the results were assessed after 7 and 14 days of treatment.
 Results: In all cases, dermatoscopy of the vulgar psoriasis lesions showed vermilion or red to rosy background with evenly distributed dotted vessels and white scales diffusely located all over the visualized surface. The skinfold lesions were characterized by rosy or red background with evenly distributed dotted vessels, white scales located either as isolated groups, or at the periphery of the visualized areas; some plaques had local erosions, and in one case, hemorrhages. Morphological assessment of the biopsy samples in all patients with isolated skinfold lesions (n = 5) confirmed the diagnosis of psoriasis. Treatment-induced improvement was seen at day 2 to 3, and at day 14, there was a decrease of M-PASI by 90% in 6 (40%) patients and resolution of the lesions in 9 (60%). There were no treatment-associated adverse events or reactions.
 Conclusion: Dermatoscopy has proved to be a useful tool for non-invasive diagnostics of inverse psoriasis. At low magnification ( 20), its main sign was an even distribution of dotted vessels throughout the visualized area. In a number of cases, the dermatoscopic symptoms additionally included white scales grouped as isolated foci. The addition of the combination topical agent (mometasone furoate, gentamicin sulfate, econazole nitrate, and dexpanthenol) to the standard systemic therapy facilitated almost full resolution of skinfold psoriatic lesions.

Human dental pulp stem cells ameliorate the imiquimod-induced psoriasis in mice

Psoriasis is an autoimmune disease, which has a significant impact on the quality of patient’s life. And, there is still no cure for psoriasis. The human dental pulp stem cell (hDPSC) possesses the properties of immunoregulation. In this study, we aimed to determine the effect of hDPSC on the imiquimod (IMQ)-induced psoriasis in mice. The psoriasis model was established by topical application of IMQ cream in mice for 7 days. We found that subcutaneous injection of hDPSC could reduce the symptoms of skin lesions in IMQ-induced psoriasis and suppress the expression of keratin 16, S100A8, S100A9, which are associated with abnormal epidermal proliferation. Subepithelial inflammatory cytokines, CD4+ T lymphocytes and CD11c+ dendritic cells infiltrations were significantly inhibited in by hDPSC. The TNF-α, IFN-γ expressions in serum were decreased, and splenomegaly induced by IMQ was improved after hDPSC treatment. In summary, our study demonstrated that hDPSC could reduce the symptoms of skin lesions and suppress local and systemic immune responses of IMQ-induced psoriasis in mice, which might provide a new sight for the treatment of psoriasis.

Integrative medicine (East Asian herbal medicine combined with conventional medicine) for psoriasis: A protocol for systematic review and meta-analysis.

Psoriasis is a chronic, inflammatory, autoimmune skin disease. The aim of this review is to systematically evaluate the efficacy and safety of integrative medicine (East Asian herbal medicine combined with conventional medicine) used to treat inflammatory skin lesions of psoriasis. A comprehensive literature search will be conducted in 3 English databases (PubMed, Cochrane Library, and Embase), 4 Korean databases (Korean Studies Information Service System, Research Information Service System, Oriental Medicine Advanced Searching Integrated System, and Korea Citation Index), 2 Chinese databases (Chinese National Knowledge Infrastructure Database and Wanfang data), and 1 Japanese database (Citation Information by National Institute of Informatics) for randomized controlled trials from their inception until July 29, 2021. Statistical analysis will be performed using R version 4.1.2 and the R studio program using the default settings of the "meta" and "metafor" packages. The primary outcome will be an improvement in the psoriasis area severity index. All outcomes will be analyzed using a random-effects model to produce more statistically conservative results. If heterogeneity is detected in the study, the cause will be identified through sensitivity, meta-regression, and subgroup analyses. Methodological quality will be assessed independently using the revised tool for the risk of bias in randomized trials, version 2.0. The overall quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation pro framework. This study will review all available trials on the same subject and arrive at a more statistically robust conclusion based on a sufficient sample size of participants and additional analysis using data mining techniques will be performed on intervention prescription information in clinical studies collected according to rigorous criteria. We believe that this study will provide useful knowledge on managing inflammatory skin lesions of psoriasis vulgaris using integrative medicine using East Asian herbal medicine.

The correlation between patient satisfaction treatment of narrowband ultraviolet B phototherapy and the improvement of psoriasis severity index

Background: Psoriasis is a chronic inflammatory disease of the skin affecting patients of all ages, both males and females. Currently, the psoriasis area and severity index (PASI) method is the gold standard in assessing the severity of psoriasis. Phototherapy narrowband ultraviolet B (NBUVB) is one of the modalities of psoriasis therapy which is relatively safe and effective for repairing psoriasis lesions. Patient satisfaction with phototherapy, which can be assessed using a questionnaire, serves to determine the patient's motivation in carrying out routine therapy. 
 Objective: This study was designed to determine the correlation between the level of NBUVB phototherapy satisfaction with PASI improvement.
 Method: The study subjects were 22 plaque-type psoriasis vulgaris patients who underwent NBUVB phototherapy from May 2018 to October 2018 in the dermatovenereology outpatient clinic of Dr. Moewardi Hospital Surakarta. Subjects filled in the Treatment Satisfaction Questionnaire for Medication (TSQM) included questions about satisfaction with NBUVB phototherapy, and PASI scores were measured before and after NBUVB phototherapy. 
 Results: The data were analyzed with the Pearson correlation test with a significance value of p <0.05. There are significant differences between PASI before and after giving 24 times phototherapy with a value of p<0.05. 
 Conclusion: There was a significant correlation between the degree of PASI improvement and the global patient satisfaction with NBUVB phototherapy

Effects of Neuropeptides on Dendritic Cells in the Pathogenesis of Psoriasis

Psoriasis is an autoimmune disease that is characterized by discolored, scaled patches of skin. Clinically, it is found that psychological factors often induce or aggravate the disease. Current research suggests that the pathogenesis of psoriasis involves the nervous and immune systems. This article reviews how neuropeptides secreted by nerve fibers affect dendritic cells in psoriasis. In this review, we describe that the neuropeptides calcitonin gene-related peptide, substance P, and vasoactive intestinal peptide can act on dendritic cells and participate in the pathogenesis of psoriasis. These neuropeptides can affect the secretion of interleukin (IL)-12 and IL-23 by dendritic cells, which stimulate T helper (Th)1, Th17, and Th22 cells to produce immune responses and cause the manifestation of psoriasis. The application of neuropeptide inhibitors can improve the skin lesions of psoriasis, which has been confirmed in clinical trials. Therefore, neuroimmune response may be a new direction to develop new drug treatments and perspectives in the development of psoriasis.

Retracted: Study on the Correlation between Morphology and Distribution of Common Psoriasis Lesions.

[This retracts the article DOI: 10.1155/2022/6963630.].

Sericin-Based Poly(Vinyl) Alcohol Relieves Plaque and Epidermal Lesions in Psoriasis; a Chance for Dressing Development in a Specific Area

The noncontagious immune-mediated skin disease known as psoriasis is regarded as a chronic skin condition with a 0.09-11.4% global prevalence. The main obstacle to the eradication of the disease continues to be insufficient treatment options. Sericin, a natural biopolymer from Bombyx mori cocoons, can improve skin conditions via its immunomodulatory effect. Many external therapeutic methods are currently used to treat psoriasis, but sericin-based hydrogel is not yet used to treat plaques of eczema. Through the use of an imiquimod rat model, this study sought to identify the physical and chemical characteristics of a silk sericin-based poly(vinyl) alcohol (SS/PVA) hydrogel and assess both its therapeutic and toxic effects on psoriasis. The cytokines, chemokines, and genes involved in the pathogenesis of psoriasis were investigated, focusing on the immuno-pathological relationships. We discovered that the SS/PVA had a stable fabrication and proper release. Additionally, the anti-inflammatory, antioxidant, and anti-apoptotic properties of SS/PVA reduced the severity of psoriasis in both gross and microscopic skin lesions. This was demonstrated by a decrease in the epidermal histopathology score, upregulation of nuclear factor erythroid 2-related factor 2 and interleukin (IL)-10, and a decrease in the expression of tumor necrosis factor (TNF)-α and IL-20. Moreover, the genes S100a7a and S100a14 were downregulated. Additionally, in rats given the SS/PVA treatment, blood urea nitrogen, creatinine, and serum glutamic oxaloacetic transaminase levels were within normal limits. Our findings indicate that SS/PVA is safe and may be potentiated to treat psoriasis in a variety of forms and locations of plaque because of its physical, chemical, and biological characteristics.

The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis

In recent years, a growing interest in the characterization of the molecular basis of psoriasis has been observed. However, despite the availability of a large amount of molecular data, many pathogenic mechanisms of psoriasis are still poorly understood. In this study, we performed an integrated analysis of 23 public transcriptomic datasets encompassing both lesional and uninvolved skin samples from psoriasis patients. We defined comprehensive gene co-expression network models of psoriatic lesions and uninvolved skin. Moreover, we curated and exploited a wide range of functional information from multiple public sources in order to systematically annotate the inferred networks. The integrated analysis of transcriptomics data and co-expression networks highlighted genes that are frequently dysregulated and show aberrant patterns of connectivity in the psoriatic lesion compared with the unaffected skin. Our approach allowed us to also identify plausible, previously unknown, actors in the expression of the psoriasis phenotype. Finally, we characterized communities of co-expressed genes associated with relevant molecular functions and expression signatures of specific immune cell types associated with the psoriasis lesion. Overall, integrating experimental driven results with curated functional information from public repositories represents an efficient approach to empower knowledge generation about psoriasis and may be applicable to other complex diseases.

Characteristics and pathogenesis of Koebner phenomenon.

The Koebner phenomenon, also known as isomorphic reaction, refers to the development of secondary lesions with the same clinical manifestations and histopathological characteristics as the primary lesions in normal skin after trauma or other stimuli. The triggering factors of Koebner phenomenon include physical trauma, chemical stimulation, mechanical stress, iatrogenic stimulation and pathogenic infection. Vitiligo, psoriasis and lichen planus are considered true Koebner phenomenon. Recent studies have shown that immunological disorders, oxidative stress, defective melanocyte adhesion and growth factor deficiency are the main pathological mechanisms of vitiligo Koebner phenomenon. In psoriasis, triggers may drive skin inflammation to induce a psoriatic phenotype through multiple signalling pathways and thereby cause Koebner phenomenon in susceptible individuals. Significantly, keratinocytes mediate the occurrence of Koebner phenomenon in psoriasis through mechano-induced signalling pathways after sensing mechanical signals and explains the high frequency of psoriasis lesions on the extensor side of the elbow and knee joints. On the contrary, TRPA1-driven mechano-transduction, autoimmunity and actinic damage are the underlying mechanisms of Koebner phenomenon in lichen planus. In this review, we have summarized the current understanding of the characteristics and pathogenesis of Koebner phenomenon.

Treatment Persistence of Ixekizumab in Adults with Moderate-to-Severe Plaque Psoriasis Participating in the Canadian Patient Support Program.

Patients with psoriasis (PsO) should adhere to and be persistent with treatment to maintain disease control. Patient support programs (PSPs) are useful to support patients with disease management. We aimed to understand the real-world patient profile and persistence of ixekizumab-initiating Canadian patients with moderate-to-severe PsO using PSP data. This retrospective observational study was conducted utilizing a Canadian PSP database (May 2016 to March 2020). Inclusion criteria were: age ≥ 18years with moderate-to-severe PsO, initiated ixekizumab, enrolled in the PSP for ≥ 6months, and provided informed consent. Psoriasis Area Severity Index (PASI), body surface area (BSA) involvement, and Dermatology Life Quality Index (DLQI) were collected at PSP entry. Adherence [using the proportion of days covered (PDC)] and persistence (using Kaplan-Meier curves) were assessed after 1-year and 2-year follow-ups. Differences in persistence between biologic-naïve and biologic-experienced patients were compared using Cox proportional hazards model after adjusting baseline parameters. In total, 1891 ixekizumab-treated moderate-to-severe patients with PsO were included. The mean [standard deviation (SD)] age was 52.3 (13.3) years; 51.1% of patients were 45-65years old and 61.4% were male. At baseline, the mean (SD) PASI score was 14.3 (8.1), the DLQI score was 16.5 (7.7), and BSA % was 17.4 (15.1). PsO lesions were commonly located on the hands (33.4%), face (28.6%), and feet (23.8%). Ixekizumab-treated patients were highly adherent [PDC ≥ 80%: 1-year (92.0%), 2-year (87.7%)] and persistent [1-year (90.4%), 2-year (85.6%)]. Biologic-naïve patients were more adherent (1-year, 94.6% versus 87.3%; 2-year, 90.3% versus 83.5%) than biologic-experienced patients. Significantly higher persistence in biologic-naïve versus biologic-experienced patients for 1-year (p < 0.01) and 2-year (p = 0.010) follow-up periods was observed after adjusting for baseline parameters. Patients with moderate-to-severe PsO overwhelmingly remained on ixekizumab treatment for more than 2years while participating in a PSP.

225 Possible mechanism underlying hypopigmentation in psoriatic lesion

Vitiligo is sometimes complicated with psoriasis, and more frequently, pigmentation or depigmentation arises after psoriatic lesion subsides. It is not clear whether melanocyte function is maintained in psoriasis, which is characterized by keratinocyte proliferation, and how melanin migration to keratinocytes is affected, and we will discuss the behavior of pigment cells in psoriasis lesions. Melanin-containing cells were observed mainly in the basal layer in the uninvolved lesions and normal control skin, but few melanin-containing cells were found in the psoriasis lesions.

Effectiveness and safety of auricular acupuncture for psoriasis: A protocol for systematic review and meta-analysis.

Psoriasis is a chronic, immune-mediated, polygenic skin disease that is common in clinical practice and often develops on the extremities, back, and scalp of patients. In that psoriasis lesions are stubborn and prone to recurrence, it has a serious impact on patients' quality of life and is detrimental to their physical and psychological health. Auricular acupuncture is one of the traditional Chinese medical treatments, which has the advantages of low adverse effects and simple operation and has been widely used in clinical practice with good efficacy. However, there has been no systematic evaluation of auricular acupuncture in the treatment of psoriasis. This protocol aims to evaluate the effectiveness and safety of auricular acupuncture in patients with psoriasis. We will search the following 8 databases including PubMed, MEDLINE, EMBASE, Cochrane Library, CNKI, Wan Fang, VIP, and CBM databases for randomized controlled trials of auricular acupuncture treated psoriasis from their inception to 10 October 2022. We will analyze the data meeting the inclusion criteria with the RevMan V.5.4 software. Two authors will assess the quality of the study with the Cochrane systematic evaluation tool. Treatment effectiveness and the psoriasis area and severity index are defined as the main outcomes, and the additional outcomes include itchy, dermatology life quality index, relapse rate, and adverse events. This study will review and evaluate the available evidence on the effectiveness and safety of auricular acupuncture for psoriasis. The results of this study will provide evidence for the effectiveness and safety of treating psoriasis, providing clinicians and patients with appropriate treatment options for this disease.