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Purpose: To characterize the active components and molecular mechanisms of action of Xiaoyin Granule (XYG), and also to determine its synergistic effect with acitretin on psoriasis. Methods: Bioactive targets of XYG, acitretin targets, and psoriasis-related targets were retrieved from public databases. Key bioactive compounds and targets were identified by bioinformatic and network pharmacology analysis. The binding affinities between bioactive compounds and crucial targets were evaluated through molecular docking analysis. Results: A comprehensive screening of XYG revealed the identification of 323 bioactive compounds and 324 corresponding targets. A total of 47 acitretin targets and 1706 psoriasis-related targets were identified. Venn plot identified 155 candidate targets that contributed to the synergistic effects of XYG and acitretin against psoriasis. Bioinformatics analysis demonstrated that the candidate targets were associated with diverse pathways that participate in signaling transduction. A clustering analysis of protein-protein interaction (PPI) revealed the presence of three distinct clusters, with cluster 3 exhibiting a significant association with immunity and potentially serving a crucial function in the therapeutic mechanisms of XYG and acitretin capsule in the treatment of psoriasis. A herb-compound-target-pathway network was constructed and revealed a variety of bioactive compounds, including quercetin, apigenin, and luteolin, and targets, viz, PTGS2, PRKACA, and MAPK14. Molecular docking demonstrated that the key bioactive compounds had favorable binding affinities with hub targets. Conclusion: This study provides insights into the potential mechanisms underlying the therapeutic effects of XYG when combined with acitretin capsules for treatment of psoriasis, thus laying a solid foundation for further investigations into its mechanism and clinical applications.

Psoriasis management may be challenging, particularly for moderate-to-severe forms of the disease. Indeed, conventional systemic treatments are often avoided for contraindications or the risk of adverse events as well as phototherapy is often limited by logistic concerns. Despite the development of biological drugs and small molecules revolutionized the treatment options showing promising results in terms of safety and effectiveness, some limitations remain. Thus, there is still a need for new therapies that are always welcome in order to tailor the treatment to the patient and to have a higher level of performance, especially in order to maintain long-term effectiveness. In this scenario, deucravacitinib, an oral small molecule which selectively inhibits Tyrosine Kinase 2, may represent a promising weapon in psoriasis management. The aim of our manuscript is to review the current knowledge on the efficacy and safety of deucravacitinib for the management of psoriasis.

The coexistence of psoriasis and hidradenitis suppurativa (HS) has been described, but the association between these conditions is yet to be firmly established.To study the association between psoriasis and HS using a large-scale real-life computerized database.A cross-sectional study was conducted comparing the prevalence of HS among patients with psoriasis and among age-, sex- and ethnicity-matched control subjects.A total of 68,836 patients with psoriasis and 68,836 controls were included in the study. The prevalence of HS was increased in patients with psoriasis as compared to the control group (0.3% vs. 0.2%, respectively; OR, 1.8; 95% CI, 1.5-2.3; P0.001). In a multivariate analysis adjusting for smoking, obesity, and other comorbidities, psoriasis was still associated with HS (OR, 1.8; 95% CI, 1.4-2.2; P0.001). Patients with coexistent psoriasis and HS were significantly younger (39.0±15.7 vs. 42.6±21.2 years; P=0.015) and had a higher prevalence of obesity (35.1% vs. 25.3%; P=0.001) and smoking (58.5% vs. 37.3%; P0.001) as compared to patients with psoriasis alone.Retrospective data collection.A positive association was observed between HS and psoriasis. Further longitudinal observational studies are necessary to establish these findings in other study populations.

Marina Talamonti,1 Filomena Russo,2 Giovanna Malara,3,4 Katharina Hansel,5 Manuela Papini,6 Angelo Cattaneo,7 Aurora Parodi,8 Andrea Chiricozzi,9,10 Piergiorgio Malagoli,11 Federico Bardazzi,12 Valeria Brazzelli,13 Paolo Dapavo,14 Paolo Gisondi,15 Cristina Zane,16 Concetta Potenza,17 Franca Cantoresi,18 Maria Concetta Fargnoli,19 Sara Trevisini,20 Pina Brianti,21 Leonardo Pescitelli,22 Giovanni Gigante,23 Marta Bartezaghi,23 Luisa Caputo,23 Elisabetta Aloisi,23 Antonio Costanzo24,25 On behalf of the SUPREME Study Group1Dermatology, University of Rome Tor Vergata, Rome, Italy; 2Department of Medical, Surgical and Neurological Science, Dermatology Section, University of Siena, S. Maria alle Scotte Hospital, Siena, Italy; 3Dermatology Unit, Hospital “Bianchi Melacrino Morelli”, Reggio, Calabria, Italy; 4Department of Dermatology, Papardo Hospital, Messina, Italy; 5Section of Dermatology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; 6Dermatologic Clinic of Terni, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; 7U.O. Dermatologia, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milano, Italy; 8Di.S.Sal. Section of Dermatology, Ospedale Policlinico San Martino, University of Genova, Genova GE, 16132, Italy; 9UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy; 10Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; 11Psocare Unit, I.R.C.C.S Policlinico San Donato, Milano, Italy; 12Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 13Dermatology, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy; 14Department of Biomedical Science and Human Oncology, Second Dermatologic Clinic, University of Torino, Torino, Italy; 15Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy; 16Dermatology Department, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy; 17Dermatology Unit “Daniele Innocenzi”, Department of Medico-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome – Polo Pontino, Latina, Italy; 18Dermatology Unit, Department of Medicine, University of Roma, Roma, Italy; 19Dermatology, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy; 20Department of Dermatology, University of Trieste, Trieste, Italy; 21Dermatology and Cosmetology Unit - San Raffaele Hospital, Milan, Italy; 22Department of Health Sciences, Dermatology Clinic, University of Firenze, Firenze, Italy; 23Novartis Farma SpA, Origgio, Italy; 24Unit of Dermatology, IRCCS Humanitas Research Hospital, Milano, Italy; 25Department of Biomedical Sciences, Humanitas University, Milano, ItalyCorrespondence: Marina Talamonti, Dermatology-Department of Systems Medicine, University of Rome Tor Vergata, PTV – Policlinico Tor Vergata, V.le Oxford 81, Rome, 00133, Italy, Tel +39 0620902743, Fax +39 0620902742, Email talamonti.marina@gmail.comPurpose: Secukinumab is a fully human monoclonal antibody that inhibits interleukin (IL)-17A approved for the treatment of moderate to severe plaque psoriasis in adults and children. We compared the efficacy and safety of secukinumab in patients aged < 65 years (adult patients) versus patients aged ≥ 65 years (elderly patients) in a post-hoc analysis of the SUPREME study.Patients and Methods: Patients with moderate to severe plaque psoriasis received subcutaneous secukinumab 300 mg per week for the first 5 weeks, then 300 mg per month. We compared the following outcomes in patients aged ≥ 65 years vs < 65 years: baseline characteristics; PASI50/75/90/100 response rates (improvements ≥ 50%/75%/90%/100% in Psoriasis Area and Severity Index (PASI) from baseline); changes in Dermatology Life Quality Index (DLQI); Hospital Anxiety and Depression Scale (HAD-A, HAD-D) score changes; treatment-emergent adverse events (TEAEs).Results: Secukinumab was slightly less effective in elderly patients than in adult patients (response rates at week 16: PASI90, 69.4% vs 80.9%, p = 0.4528; PASI100, 44.4% vs 56.7%, p = 0.8973). Elderly and adult patients showed a similar time course of changes in absolute PASI scores. Patients aged ≥ 65 years had a statistically significantly lower improvement in quality of life (mean DLQI reduction) than patients aged < 65 years at week 16 [− 5.4 (± 4.3) vs − 8.8 (± 6.9), p = 0.0065] and at week 24 [− 5.3 (± 4.4) vs − 9.2 (± 7.1), p = 0.0038]. Secukinumab treatment resulted in comparable mean reductions in anxiety and depression scores in both cohorts at 24 weeks [HAD-A, − 1.3 (± 3.3) vs − 2.1 (± 3.8), p = 0.9004; HAD-D, − 1.0 (± 3.3) vs − 1.5 (± 3.1), p = 0.4598]. The frequency of TEAEs in the two cohorts was similar (16.7% vs 14.6%, p = 0.7391).Conclusion: Secukinumab is a valid option for the management of moderate to severe psoriasis in elderly patients.Keywords: psoriasis, biologics, interleukin-17A, secukinumab, elderly

Background: Confirmatory data on long-term effectiveness and safety of ixekizumb in psoriatic patients from real-world studies are needed. Objectives: The primary aim was to evaluate the 3-year drug survival of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis, in a multicenter real-world setting. The secondary aim was to assess the influence of predictive factors on the drug survival of ixekizumab. Methods: A retrospective analysis was performed on a cohort of patients with chronic plaque psoriasis, who received at least one dose of ixekizumab before December 2018. The drug survival analysis was performed, descriptively analyzed using Kaplan-Meier survival curves. Multivariable Cox regression analyses were carried out including variables considered of clinical importance. Results: A total of 306 patients was enrolled. The overall drug survival at 12, 24 and 36 months of treatment with ixekizumab was 92.11%, 83.85% and 80.19%, respectively. A higher probability (HR 2.34) of drug withdrawal was found among patients who had already received an anti-IL-17 agent compared with bio-naive patients (p 0.017). Conclusions: We found that ixekizumab is a biological agent characterized by a long term effectiveness, not influenced by several clinical factors and associated with a good safety profile.

Background: In psoriasis, poor treatment adherence is frequently related to low efficacy and limited cosmetic acceptability from the patients' perspective. This study aimed to characterize the sensorial attributes of a calcipotriol (CAL) and betamethasone dipropionate (BDP)-cream vehicle based on polyaphron dispersion (PAD) Technology and to compare them with the conventional ointment and oleogel formulations for psoriasis. Methods: A panel of 16 experts assessed sensory properties at four different stages: appearance, pick up, rub out and afterfeel. Descriptive sensory analysis was used to evaluate relevant attributes. Each attribute was rated on a line scale (range 0-100%). Active ingredients were not used because panellists were healthy volunteers, and vehicle formulations needed to be used instead. Results: CAL/BDP PAD-cream vehicle was evaluated as having a low stickiness, low grease behaviour, good wetness, and good spreadability. Ointment showed the least desirable behaviour regarding these properties. Moreover, once CAL/BDP PAD-cream vehicle was absorbed, the gloss disappeared quickly, leaving low stickiness and a low amount of residue. This afterfeel behaviour was not observed with ointment. The oleogel formulation had good sensory properties, similar to CAL/BDP PAD-cream vehicle, but with lower integrity of shape, lower wetness and higher greasiness. Conclusion: Overall, CAL/BDP PAD-cream vehicle has the desirable requirements for a topical product for the treatment of psoriasis, with better sensory properties than ointment and easier manipulation than oleogel, which may lead to greater acceptance and adherence.

Background: Biologic selection for psoriasis treatment should take into account numerous factors including injection site reactions (ISRs) such as swelling at the injection site, pain, burning, erythema, all possibly reducing patient adherence. Methods: A 6-months observational real life study was performed involving psoriasis patients. Inclusion criteria were age ≥ 18 years, moderate-to-severe psoriasis diagnosis since at least 1 year, patients being on biologic treatment for psoriasis ≥ 6 months. A 14-item questionnaire was administered to all patients enrolled to assess whether the patient ever experienced ISRs after the injection of the biologic drug. Results: 234 patients were included: 32.5% received an anti-TNF-alpha drug, 9.4% received anti-IL12/23, 32.5% received an anti-IL17, 25.6% received an anti-IL23. 51.2% of study population reported at least one symptom related to ISR. 35.9% of patients experienced pain, 31.6% swelling, 28.2% burning sensation and 17.9% erythema. 3.4% of the surveyed population experienced anxiety or fear of the biologic injection due to ISRs symptoms. The greater incidence of pain was registered in anti-TNF-alpha and anti-IL17 groups (47.4% and 42.1%, p

The aim of the workis to analyze the use of medicines containing retinoids for the treatment of psoriasis on the example of Ukraine, Poland and Kazakhstan. Materials and methods.The object of the study was antipsoriatic drugs, which are used for the treatment of psoriasis of local and systemic action, and are included in the official register of drugs of the studied countries. Regulatory documents of the State Expert Center of the Ministry of Health of Ukraine were involved in the analysis of the use of medicines for the treatment of psoriasis in Ukraine. The analysis of the availability of the considered medicines on pharmaceutical markets was carried out according to the data of the official websites of the State Register of Medicines (Ukraine), the Register of Medicines of Poland (Republic of Poland), data of the National Center for Expertise of Medicines and Medical Devices of the Republic of Kazakhstan (Republic of Kazakhstan). The following methods of logical and meaningful formulation of the problem, office marketing research, content analysis of publications in scientific and practically oriented medical and pharmaceutical publications, comparative analysis, tabular and graphic means of visual presentation of the obtained data were used in the work. The results.According to the results of the obtained data, an assortment of medicinal products containing retinoids of the studied countries, used for the treatment of psoriasis, was determined. The fate of domestic production in the countries was analyzed, the main active components from the group of retinoids used for the treatment of psoriasis in preparations of systemic and local action were updated. Conclusions.The role of retinoids in the treatment of psoriasis in Ukraine, Poland and Kazakhstan and the need to develop modern domestic medicines containing retinoids for the treatment of psoriasis have been determined

Psoriasis still has an unknown etiology. Genetic predisposition shows the association between HLA-Cw6 allele and psoriasis. Although biotherapies have been proven effective in psoriasis treatment, methotrexate (MTX) is still used as a first-line systemic therapy due to its efficacy/affordability, but the differential response to MTX is mostly related to interindividual genetic variability and remains an issue. Our study aimed to analyze HLA-C allele frequencies in a sample of Moroccan psoriatic patients and assess the therapeutic response to MTX. Whole blood of 54 Moroccan psoriatic patients was collected and DNA was extracted. Patients’ HLA-C locus was genotyped by PCR-SSO. Results were analyzed with Luminex xMAP Technology and Match-it DNA Evolution 3.4. HLA-C typing results of 77 sex- and age-matched unrelated non-psoriatic healthy subjects were included. We observed no difference in the allelic distribution of HLA-C between patients and healthy controls, suggesting that none of the HLA-C alleles were significantly associated with psoriasis. Moreover, the HLA-C*07 allele was associated with a late age at disease onset (>30 years old) (p = 0.007). No statistically significant association was found between HLA-C allele expression and response to MTX, despite a higher frequency of HLA-C*06 in responders compared to non-responders. Thus, HLA-C*07 could be a biomarker of late psoriasis onset in the Moroccan population.

BackgroundThe association of alcohol with psoriasis has been inconsistent among studies.ObjectivesWe aimed (1) to determine whether alcohol consumption (by status, frequency, and subtype of alcohol) modulates smoking-related psoriasis risk in postmenopausal women while stratifying for smoking status and pack-years and (2) to evaluate the effect of smoking cessation on psoriasis risk in postmenopausal women.MethodsThis prospective cohort study included 106,844 postmenopausal women enrolled in the Women's Health Initiative between 1993 and 1998. Patients diagnosed with psoriasis were identified using fee-for-service Medicare International Classification of Diseases, Ninth Revision, Clinical Modification codes assigned by dermatologists or rheumatologists. Self-administered questionnaires were used to obtain information on demographics, medical history, and smoking and alcohol habits. Hazard ratios from Cox regression models were adjusted for ethnicity, income, body mass index, and history of non-melanoma skin cancer and were stratified on age and on randomization status in the Women's Health Initiative study components.ResultsIn the initial statistical model, past and current alcohol drinkers had higher risks of psoriasis compared with never-drinkers (P-trend < 0.001). This association was not observed after adjusting for cigarette smoking (P-trend: 0.478). The effect of alcohol (by status, frequency, and alcohol subtype) isolated by stratifying the analysis by smoking status (i.e., among never smokers) showed no association with psoriasis. Smoking showed an increasing risk for psoriasis with greater pack-years compared with those who have never smoked (P-trend: < 0.001). Compared to smokers at baseline, past smokers had a lower risk of psoriasis across women who smoked 5-14 cigarettes per day (hazard ratio 0.67, 95% confidence interval 0.51-0.88) and across women who smoked for 5-24 years (hazard ratio 0.65, 95% confidence interval 0.46-0.90).ConclusionsThese findings indicate that alcohol consumption does not modulate smoking-related psoriasis risk. Cigarette smoking, but not alcohol consumption, is an independent risk factor for psoriasis in postmenopausal women. As greater pack-years was associated with a higher risk of psoriasis and smoking cessation was conversely associated with a lower risk of psoriasis for moderate smokers, a greater emphasis on smoking abstinence and cessation counseling may benefit patients who already have other risk factors for psoriasis.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, inhibits cytokine signaling in psoriasis pathogenesis.The objective of this study was to demonstrate deucravacitinib superiority versus placebo and apremilast in moderate to severe plaque psoriasis based on ≥75% reduction from baseline in Psoriasis Area and Severity Index and a static Physician's Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline at week 16.POETYK psoriasis second trial (NCT03611751), a 52-week, double-blinded, phase 3 trial, randomized patients 2:1:1 to deucravacitinib 6 mg every day (n = 511), placebo (n = 255), or apremilast 30 mg twice a day (n = 254).At week 16, significantly more deucravacitinib-treated patients versus placebo and apremilast patients achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index (53.0% vs 9.4% and 39.8%; P .0001 vs placebo; P = .0004 vs apremilast) and static Physician's Global Assessment score of 0 or 1 (49.5% vs 8.6% and 33.9%; P .0001 for both). Efficacy was maintained until week 52 with continuous deucravacitinib. The most frequent adverse event with deucravacitinib was nasopharyngitis. Serious adverse events and discontinuations due to adverse events were infrequent. No clinically meaningful changes were observed in laboratory parameters.The study duration was 1 year.Deucravacitinib demonstrated superiority versus placebo and apremilast and was well tolerated in adults with moderate to severe plaque psoriasis.

Data on predictors and time to relapse in patients with psoriasis who discontinue therapy in a real-world setting are scarce.To investigate predictors of relapse after withdrawal of ustekinumab in patients with psoriasis.This study screened 500 patients with psoriasis who received ustekinumab (669 treatment episodes) between 2011 and 2018. Overall, 202 patients (accounting for 304 treatment episodes) who had responded to therapy and were withdrawn from ustekinumab treatment were included.The cumulative probabilities of being relapse-free at 6, 12, 18, 24, and 36 months after withdrawal from ustekinumab treatment were 49.3%, 12.6%, 5.3%, 4.7%, and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologic-naive status, maximum improvement in Psoriasis Area and Severity Index during ustekinumab treatment, time to achieve a 50% improvement in baseline Psoriasis Area and Severity Index score after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressant use while not taking ustekinumab were significant predictors of time to relapse following discontinuation of ustekinumab.Nonrandomized allocation of duration of treatment and follow-up.Given the high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended.

FK506 is a local drug that is commonly used in the treatment of psoriasis. Its clinical application, however, is limited by its transdermal drug delivery rate, the time-consuming, and the greasy therapy. In this study, which was inspired by local block injection used in the clinical treatment for keloid, a hyaluronic acid (HA) based system to transport FK506 into the skin to treat psoriasis, named blocking patch (BP) was developed. BP has a complete appearance, sufficient puncture strength, and is virtually non-irritating in vivo. By confocal fluorescence microscopy, BP loaded with FK506 (FK506-BP) showed satisfactory transdermal release ability in vivo. Further animal studies revealed that FK506-BP showed a good anti-inflammatory ability in the imiquimod (IMQ)-induced mouse psoriasis-like dermatitis and inhibited the activation of associated immune cells. This study indicates that BP as a novel delivery system, realizes an efficient local delivery of FK506 in psoriasis and holds great potential in transdermal delivery.

Background The pathogenesis of psoriasis vulgaris involves changes in DNA molecules, genomic instability, telomere attrition, and epigenetic alterations among them. These changes are also considered important mechanisms of aging in cells and tissues. Objective This study dealt with oxidation damage, telomere length and methylation status in DNA originating from peripheral blood of 41 psoriatic patients and 30 healthy controls. Methods Oxidative damage of serum DNA/RNA was determined immunochemically. Real-time PCR was used for the analysis of the telomere length. ELISA technique determined levels of 5-methylcytosine in blood cells' DNA. Results Oxidative damage of serum DNA/RNA was higher in patients than in controls (median, 3758 vs. 2286 pg/mL, p < 0.001). A higher length of telomeres per chromosome was found in patients whole-cell DNA than in controls (3.57 vs. 3.04 kilobases, p = 0.011). A negative correlation of the length of telomeres with an age of the control subjects was revealed (Spearman’s rho = -0.420, p = 0.028). Insignificantly different levels of 5-methylcytosine in patients and controls were observed (33.20 vs. 23.35%, p = 0.234). No influences of sex, smoking, BMI, PASI score, and metabolic syndrome on the methylation status were found. Study limitations i) A relatively small number of the participants, particularly for reliable subgroup analyses, ii) the Caucasian origin of the participants possibly influencing the results of the parameters determined, and iii) Telomerase activity was not directly measured in serum or blood cells. Conclusion The study demonstrated increased levels of oxidized DNA/RNA molecules in the serum of patients with exacerbated psoriasis vulgaris. The results were minimally influenced by sex, the presence of metabolic syndrome, or cigarette smoking. In the psoriatic blood cells' DNA, the authors observed longer telomeres compared to healthy controls, particularly in females. Insignificantly higher global DNA methylation in psoriasis cases compared to the controls indicated marginal clinical importance of this epigenetic test performed in the blood cells' DNA.

Contains fulltext : 291154.pdf (Publisher’s version ) (Open Access) AIMS: In immune-mediated inflammatory diseases (IMIDs), early symptom control is a key therapeutic goal. Methotrexate (MTX) is the first-line treatment across IMIDs. However, MTX is underutilized and suboptimally dosed, partly due to the inability of making individualized treatment decisions through therapeutic drug monitoring (TDM). To implement TDM in clinical practice, establishing a relationship between drug concentration and disease activity is paramount. In this meta-analysis, we investigated the relationship between concentrations of MTX polyglutamates (MTX-PG) in erythrocytes and efficacy as well as toxicity across IMIDs. METHODS: Studies analysing MTX-PG in relation to disease activity and/or toxicity were included for inflammatory arthritis (rheumatoid [RA] and juvenile idiopathic arthritis [JIA]), inflammatory bowel disease (Crohn's and ulcerative colitis) and dermatitis (psoriasis and atopic dermatitis). Meta-analyses were performed resulting in several summary effect measures: regression coefficient (β), correlation coefficient and mean difference (of MTX-PG in responders vs. nonresponders) for IMIDs separately and collectively. RESULTS: Twenty-five studies were included. In RA and JIA, higher MTX-PG was significantly associated with lower disease activity at 3 months (β: -0.002; 95% confidence interval [CI]: -0.004 to -0.001) and after 4 months of MTX use (β: -0.003; 95% CI: -0.005 to -0.002). Similarly, higher MTX-PG correlated with lower disease activity in psoriasis (R: -0.82; 95% CI: -0.976 to -0.102). Higher MTX-PG was observed in RA, JIA and psoriasis responders (mean difference: 5.2 nmol/L MTX-PG(total) ; P

Background Psoriasis is a skin disease that affects 1.3% of Brazilians. The use of teledermatology (TD) in the public health sector has democratized access to dermatological care. Objective To analyze TD exams with suspected and/or diagnosed psoriasis performed between 2016‒2020 in the state of Santa Catarina (SC). Methods Analytical cross-sectional observational study that used secondary data collected from the records of TD exams from the Telemedicine and Telehealth System (TTS) of SC. The associations were evaluated by the chi-square test and Student'st test. The significance level was set at 5% (p < 0.05). Results During the period, 6,146 TD exams were related to psoriasis, 58% due to the diagnosis provided by the reporting dermatologist and 42% exclusively due to the suspected disease on the request of the examination. The male sex predominated among the diagnoses of dermatosis (51%; p < 0.001). Regarding risk classification, psoriasis diagnoses were predominantly yellow (58.7%; p < 0.001) or blue (39.7%; p < 0.001) risk, respectively indicating moderate to severe psoriasis (referral to tertiary care) and mild psoriasis (treatment in the primary health care [PHC] level). True positive tests, suspected by PHC and diagnosed with psoriasis through TD, were 34.1% (p < 0.001). Study limitations The TD service is available only for the public health network and analysis for a limited period (five years). Conclusions Psoriasis diagnoses performed by TD, when compared to other dermatoses, tend to receive treatment at the primary (p < 0.001) or tertiary (p < 0.001) health care level, reducing the number of referrals to the secondary care level.

The concept of nail psoriasis as an entheseal-driven disease has essentially been formulated on the basis of radiological findings because it is usually not possible to obtain the tissue directly from the joints. The aim of this retrospective study was to evaluate the histological features of isolated nail psoriasis with and without distal interphalangeal psoriatic arthritis (PsA), focusing on the question as to whether the fascia and adipose tissue surrounding the apex of the nail unit genuinely show an inflammatory infiltrate. In support of the nail-enthesitis theory, an ongoing inflammatory infiltrate could be expected. An immunohistochemical study was performed to evaluate the distribution and phenotype of the inflammatory infiltrate in nail psoriasis with and without PsA. This study did not show an inflammatory infiltrate in the fascia connecting the nail to the extensor tendon. CD8 and CD4 subsets were present in equal number in the nail dermis of nail psoriasis with or without PsA, which is a similar distribution to that seen in psoriatic synovium while skin psoriasis is characterized by a dermal predominance of CD4 T lymphocytes. Because of this study and recent microanatomic studies of the normal nail unit, it is possible to move away from a purely anatomic explanation of the strong association between nail psoriasis and PsA and to propose immunological factors as contributory. This study provides support for the hypothesis that CD8+ T cells play a crucial role in the pathogenesis of nail psoriasis through a pathogenic pathway similar to that of PsA and contrasting with that of the skin.

This article summarizes a presentation titled 'The role of topical therapies along the psoriasis patient journey' held at the Satellite Symposium of the 30

Psoriasis of the external auditory canal (PsEAC) is often under-recognized. The aims of this study were to assess the prevalence of PsEAC, its association with a particular psoriasis subtype and its impact on quality of life (QoL). A prospective study was carried out in two Spanish university hospitals, enrolling consecutive patients who attended a consultation for psoriasis. The clinical features of psoriasis and PsEAC were recorded and the Dermatology Life Quality Index (DLQI) and Itch Numerical Rating Scale (Itch-NRS) were distributed to patients. Overall, 188 of 1000 patients (18.8%) included in the study had PsEAC, which was associated with severity of psoriasis, presence of inverse psoriasis and involvement of the scalp, nails and genitals, but not with obesity or psoriatic arthritis. PsEAC was the main reason for consultation in 27 patients, with itching being the main symptom. In this study, PsEAC had a prevalence of 18.8%. The occurrence of PsEAC was associated with poorer QoL, as measured by DLQI and Itch-NRS.

Summary Background Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICIs). Objectives To investigate clinical associations of cutaneous toxicities induced by different ICI therapies. Methods This was a multicentre retrospective international cohort study of patients with cancer who developed cutaneous irAEs under ICI therapy. Analysis was performed of the rates and basic characteristics of all cutaneous toxicities, and identification of any associations was performed using univariate and multivariate models. Results In total, 762 patients were included, who developed 993 cutaneous toxicities. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23·0%) and pruritus (171 patients, 22·4%) were the most common toxicities, followed by macular rash (161 patients, 21·1%) and eczematous-type reactions (150 patients, 19·7%). Multivariate analysis showed that among patients with macular rash, vitiligo or multiple toxicities, patients received ICIs more frequently for melanoma than for NSCLC. Moreover, anti-CTLA4 was less frequent than anti-programmed death 1 treatment in patients with macular rash [odds ratio (OR) 0·11, 95% confidence interval (CI) 0·01–0·76] and vitiligo (OR 0·07, 95% CI 0·006–0·78). A significant association was also seen in patients treated with a combination of ICI and chemotherapy vs. ICI monotherapy. They less frequently developed psoriasis (OR 0·08, 95% CI 0·02–0·31), lichenoid reactions (OR 0·15, 95% CI 0·03–0·77) and eczematous reactions (OR 0·24, 95% CI 0·07–0·78), all compared with pruritic rash. Conclusions Our study showed that skin-oriented toxicities do not share a single pattern and are related to several factors, including the specific agent administered and the underlying malignancy treated. Follow-up plans should be individualized in order to minimize the risk for severe reactions that could compromise optimum therapeutic outcome. What is already known about this topic? Patients with cancer treated with different immune checkpoint inhibitors (ICIs) carry an increased risk of developing various types of skin toxicities. What are the clinical implications of this work? In this multicentre cohort study we showed that ICI-related skin toxicities do not share a single pattern and may depend on several factors, including the specific agent administered and the underlying malignancy.Among patients with macular rash, vitiligo or multiple skin toxicities, patients received ICIs more frequently for melanoma than for non-small cell lung cancer.The combination of ICI and chemotherapy compared with ICI monotherapy occurred to a lesser extent in patients with psoriatic rash lichenoid and eczematous reactions, compared with patients with pruritus.Clinical awareness and specialized dermatological consultation should be advocated.

A 30-year-old woman had recognized general fatigue and joint pain 5 years before her first visit to our hospital. Keratinized skin lesions were also observed on her hand, elbows, and other interstitial sites at the same time. She was referred to our department for evaluation of her skin eruption because psoriatic arthritis was suspected. A physical examination revealed hyperkeratotic, brownish plaques on her hand, elbows, and knees. Although a skin biopsy taken from her right hand could not confirm a diagnosis, another biopsy taken from her right elbow revealed hyperkeratosis and parakeratosis with agranulosis epithelial hyperplasia, indicating a diagnosis of psoriasis. Taking an additional skin biopsy from a site other than the main one can be helpful for a diagnosis of psoriatic arthritis.

Background Sodium–glucose co-transporter 2 inhibitor (SGLT2i) treatment may exert anti-inflammatory effects by modulating the NOD-like receptor family pyrin domain-containing 3 inflammasome and interleukin-17/23 inflammatory axis, which are both involved in the pathogenesis of psoriasis. However, the relationship between SGLT2i treatment and psoriasis remains unclear. Aim To investigate the association between SGLT2i treatment and incident psoriasis. Methods Using the Taiwan National Health Insurance Database for the period 2007–2018, we matched 103 745 patients with Type 2 diabetes mellitus (T2DM) receiving SGLT2i with a control group of patients with T2DM who did not use SGLT2i, matching them in a 1 : 2 ratio by age, sex, diabetes duration, insulin use and comorbidities, and evaluating the psoriasis risk in both groups. Results The incident psoriasis risk did not significantly differ between the SGLT2i and control groups [hazard ratio (HR) = 1.24, 95% CI 0.95–1.64] after adjustment for potential confounders. Insulin use (HR = 1.65, 95% CI 1.24–2.19) and chronic liver disease and cirrhosis (HR = 1.34, 95% CI 1.01–1.77) were significantly associated with increased psoriasis risk. A slightly increased psoriasis risk was also detected in certain SGLT2i user subgroups, especially those with renal disease (HR = 2.73, 95% CI 1.45–5.13). Conclusion SGLT2i-mediated protective effects in psoriasis could not be established. SGLT2i treatment increased psoriasis risk by 2.7-fold in patients with T2DM exhibiting renal diseases.

The aim of the study was to measure vitamin D levels before and after giving specific doses of it. Patients with psoriasis have an imbalance in vitamin D levels, as vitamin D levels have been correlated with the level of disease progression. Psoriasis incidence rates after administration of vitamin D at a dose of 1 month every day 2000 IU, then the second and third month every week 10,000 IU for period a 3-month indicate that the size of the affected area did not expand or stopped expanding. Also in our study, interleukin-17 levels and lipid profile showed some changes, indicating that high levels of vitamin D may reduce inflammation or inflammatory diseases by contributing to immune system activation. There were notable changes in average lipids and the effect was likely caused by changes in vitamin D levels, which play an important role in lipid metabolism. There was also a decrease in calcium levels.

The transition from psoriasis to psoriatic arthritis (PsA) occurs in 20-30% of patients; however, the mechanisms underlying the emergence of musculoskeletal disease are not well understood. Metabolic disease is prevalent in psoriasis patients, but whether metabolic factors, other than obesity, increase arthritis risk in psoriasis patients is not known. This study was undertaken to investigate the link between metabolic changes and disease progression in psoriasis patients.To characterize the metabolic alterations during the progression of arthritis in psoriasis patients, we analyzed cross-sectional healthy controls and PsA samples and longitudinal psoriasis serum samples, before and after PsA onset. Nontargeted metabolomic profiling was performed using liquid chromatography mass spectrometry.We identified several serum metabolites that differed between PsA patients, psoriasis patients, and healthy controls. Differentially abundant bile acids, purines, pyrimidines, glutathione, lipids, and amino acid metabolites were noted in these 3 groups. We also noted differences between psoriasis patients who progressed and those who did not progress to PsA. Bile acid and butyrate levels were depressed in those who progressed to PsA compared to those who did not, and the level of inflammatory lipid mediators increased following PsA diagnosis. In particular, the combination of leukotriene B4 and glycoursodeoxycholic acid sulfate were sensitive and specific predictors of PsA progression.We observed notable differences in bile acid, purine, lipid, and amino acid-derived metabolites, among the healthy controls, psoriasis patients, and PsA patients and identified changes during the transition from psoriasis to PsA. The decreased bile acid and butyrate levels and elevated guanine levels in psoriasis patients at risk for PsA were particularly striking and may reflect gut microbial dysbiosis and dysregulated hepatic metabolism, leading to altered proliferation of immune cells and enhanced cytokine expression.

Background: With the current trend in healthcare moving towards a more value-based approach, it is essential to understand what value encompasses. Objectives: To develop an actionable value-based outcome set (VOS) for daily practice. Methods: A mixed method approach was used consisting of four phases. Formerly, a systematic review was conducted, providing an overview of all patient-relevant outcomes defined in current literature. These 23 outcomes were then presented to a group of patients, using a modified nominal group technique (NGT), to establish whether these results represented all of their relevant outcomes. Subsequently, these outcomes were ranked according to importance by patients attending our academic specialized psoriasis clinic. A review of the literature was performed to assess which instruments were available and suitable to evaluate the outcomes in this VOS. Finally, a pilot feasibility test was performed amongst patients. Results: Of the 23 outcomes, two were omitted from the ranking exercise after the NGT. In the ranking exercise, 120 patients participated. The median age was 50.0 (IQR 25.0) years and 36.7% were female. Median PASI score was 2.4 (IQR 5.2), and treatments varied from topicals to biologicals. The outcomes scored as most important were symptom control, treatment efficacy, confidence in care and control of disease. The least important outcomes were comorbidity control, productivity and cost of care. A significant difference was shown between the ranking of the outcomes (p < 0.001). In total, 12 instruments were selected, which are reported by both patient and provider, to measure the outcomes in this VOS. Median completion time for the patient part was 30 min (IQR 2.8). Conclusions: This VOS is a first proposal to evaluate psoriasis care in a value-based manner. Measuring these outcomes can enable us to critically appraise and improve current care processes, within the reality of available resources, thereby increasing value for patients.

Although conventional topical approaches for treating psoriasis have been offered as an alternative, there are still unmet medical needs such as low skin-penetrating efficacy and off-target adverse effects. A hyaluronic acid nanoparticle (HA-NP) formed by self-assembly of HA-hydrophobic moiety conjugates has been broadly studied as a nanocarrier for long-term and target-specific delivery of drugs, owing to their excellent physicochemical and biological characteristics. Here, we identify HA-NPs as topical therapeutics for treating psoriasis using

Psoriasis is a chronic skin disease which affects about 1% of Brazilian population, with peak of incidence in both second and fifth decades of life. Psychological distress can impact physically, and physical changes can affect the psychic. This study aims to comprehend the relationship between psychic conflict and psoriasis, in adulthood, in the light of analytic psychology. This is a qualitative research, carried out with ten adults undergoing psoriasis treatment in a philanthropic hospital in northeastern Brazil. A semi-structured questionnaire was applied and from the participant’s speech three categories emerged: (1) conflicts, beginning and aggravation of symptoms; (2) the experience of negative feelings in psoriasis; and (3) variations and adaptations facing the disease. It was concluded that the findings in the research related the emergence of psoriasis to significant situations, of high affective load, confirming the current literature, besides the objective and psychic consequences to the patient.

As pro-inflammatory lipid mediators, leukotrienes have pathophysiological activities in several inflammatory diseases, including psoriasis. In the biosynthesis of leukotrienes from arachidonic acid, 5-lipoxygenase catalyzes the first two steps. In the present study, we showed that nutmeg (Myristica fragrans) strongly inhibited the catalytic activity of 5-lipoxygenase. To characterize the bioactive component(s) of nutmeg, we performed 5-lipoxygenase inhibitory activity-guided fractionation of aqueous ethanol extract of nutmeg, resulting in the isolation of malabaricone C having antioxidant activity. Malabaricone C exhibited potent competitive inhibition of 5-lipoxygenase with an IC

Psoriasis is a chronic inflammatory disease that affects up to 1 in 20 people worldwide. A patient's quality of life and health can be drastically affected by psoriasis. The number of therapies for patients with moderate to severe psoriasis has steadily grown over the past two decades, with biologic immunotherapies being the primary agents developed. However, new small-molecule oral therapies have lagged in development. Deucravacitinib is an oral small molecule that inhibits the activity of TYK2, a member of the JAK family. Deucravacitinib works by allosterically inhibiting TYK2, increasing the specificity of this agent for TYK2 rather than other members of this kinase family. Deucravacitinib has demonstrated safety and efficacy in moderate to severe plaque psoriasis in clinical trial development, with50% of patients on deucravacitinib 6 mg daily achieving ≥75% reduction in Psoriasis Area and Severity Index score from baseline at 16 weeks versus 9-13% on placebo and 35-41% on apremilast 30 mg twice daily in phase III clinical trials.Psoriasis is a chronic inflammatory disease that affects up to 1 in 20 people worldwide. A patient's quality of life and health can be drastically affected by psoriasis. The number of therapies for patients with moderate to severe psoriasis has steadily grown over the past two decades, with biologic immunotherapies being the primary medications developed. However, oral therapies have often lagged in development. Deucravacitinib is an oral small molecule that inhibits the activity of TYK2, a crucial element of the psoriasis pathway. Deucravacitinib has demonstrated safety and efficacy in moderate to severe plaque psoriasis in clinical trials and is also being studied for multiple other diseases, including Crohn's disease, ulcerative colitis, lupus (systemic, discoid and subacute cutaneous lupus erythematosus) and psoriatic arthritis.

Psoriasis is a systemic inflammatory disease with an increased risk of atherosclerotic events and premature cardiovascular disease. S100A7, A8/A9, and A12 are protein complexes that are produced by activated neutrophils, monocytes, and keratinocytes in psoriasis. Lipid-rich necrotic core (LRNC) is a high-risk coronary plaque feature previously found to be associated with cardiovascular risk factors and psoriasis severity. LRNC can decrease with biologic therapy, but how this occurs remains unknown. We investigated the relationship between S100 proteins, LRNC, and biologic therapy in psoriasis. S100A8/A9 associated with LRNC in fully adjusted models (β = 0.27, P = 0.009; n = 125 patients with psoriasis with available coronary computed tomography angiography scans; LRNC analyses; and serum S100A7, S100A8, S100A9, S100A12, and S100A8/A9 levels). At 1 year, in patients receiving biologic therapy (36 of 73 patients had 1-year coronary computed tomography angiography scans available), a 79% reduction in S100A8/A9 levels (‒172 [‒291.7 to 26.4] vs. ‒29.9 [‒137.9 to 50.5]; P = 0.04) and a 0.6 mm

Deucravacitinib (SOTYKTU™) is a first-in-class, highly selective, oral tyrosine kinase 2 (TYK2) inhibitor. It acts via an allosteric mechanism, binding to the catalytically inactive pseudokinase regulatory domain of TYK2 and stabilizing an inhibitory interaction between the regulatory and catalytic domains. Deucravacitinib is being developed by Bristol Myers Squibb for the treatment of multiple immune-mediated diseases, including psoriasis, psoriatic arthritis, lupus and inflammatory bowel disease. It received its first approval (in the USA on 9 September 2022) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. On 26 September 2022, it was subsequently approved in Japan for the treatment of plaque psoriasis, generalized pustular psoriasis and erythrodermic psoriasis. The Marketing Authorisation Application for deucravacitinib for the treatment of adults with moderate to severe plaque psoriasis has been validated in the EU, and clinical development of the drug for the treatment of multiple immune-mediated diseases is underway in numerous countries worldwide. This article summarizes the milestones in the development of deucravacitinib leading to this first approval for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Objective: Case presentation, differential diagnostic, possible therapeutic procedure and a brief literature report. Case report: An 84-year-old woman was repeatedly examined for chronic extended dermatologic lesion on lower abdomen, external genitals, perianal region, groin and adjacent inner thighs. Conclusion: Neither colposcopy with dermatovenerologic consultation, nor histopathological examination led to a precise conclusion. Only a special dermatopathologic expertise showed a diagnosis of inverse psoriasis with suggested therapy. Key words: psoriasis – vulval lesion

Treatment of inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, is undergoing transformative changes, highlighting the need to develop experimental models of skin inflammation in humans to predict treatment responses.We topically or intradermally administered four common sensitizers (dust mite (DM), diphencyprone (DPCP), nickel (Ni), and purified protein derivative (PPD)) to the backs of 40 healthy patients and the skin hypersensitivity response was biopsied and evaluated using immunohistochemistry, RNA-seq, and RT-PCR.All agents induced strong increases in cellular infiltrates (T-cells and dendritic cells) as compared to untreated skin (p .05), with variable T helper polarization. Overall, DPCP induced the strongest immune responses across all pathways, including innate immunity (IL-1α, IL-8), Th1 (IFNγ, CXCL10), Th2 (IL-5, CCL11), and Th17 (CAMP/LL37) products, as well as the highest regulatory tone (FOXP3, IL-34, IL-37) (FDR 0.01). Nickel induced Th17 (IL-17A), Th1 (CXCL10) and Th2 (IL-4R) immune responses to a lesser extent than DPCP (p .05). PPD induced predominantly Th1 (IFNγ, CXCL10, STAT1) and Th17 inflammation (IL-17A) (p .05). DM induced modulation of Th2 (IL-13, CCL17, CCL18), Th22 (IL-22), and Th17/Th22 (S100A7/9/12) pathways (p .05). Barrier defects that characterize both AD and psoriasis were best modeled by DPCP and Ni, followed by PPD, including downregulation of terminal differentiation (FLG, FLG2, LOR, LCEs), tight junction (CLDN1/CLDN8), and lipid metabolism (FA2H, FABP7)-related markers.Our data imply that DPCP induced the strongest immune response across all pathways, and barrier defects characteristic of AD and psoriasis.

In light of the lack of an agreed international standard for how to conduct cost-effectiveness analyses (CEAs), including cost-utility analyses (CUAs) from a societal perspective, there is uncertainty regarding to what extent the inclusion of productivity losses/gains in economic evaluations can affect cost-effectiveness results and subsequently decisions on whether to recommend new health technologies. To investigate this, we conducted a systematic review of CEAs and CUAs of drug-based therapies for a set of chronic immune-mediated disorders to understand how cost elements and calculation methods related to productivity losses/gains are used, examine the impact on the incremental cost-effectiveness ratio (ICER) of including productivity costs, and explore factors that affect the inclusion of productivity loss.Databases (MEDLINEOur searches identified 5016 records, culminating in 198 unique studies from 234 publications following screening. Most of the studies investigated rheumatoid arthritis (37.0%) or psoriasis (32.0%). The majority were CUAs, with some including both a CEA and a CUA (73.0%). Most studies used a payer perspective only (28.5%) or a societal perspective only (21.0%). Of the 49 studies incorporating productivity losses/gains, 42 reported the type of cost element used; all of these used patient absenteeism, either alone or in addition with other elements. Only 16 studies reported the method used to value productivity changes, of which eight used a human capital approach, four used a friction cost approach and four used both approaches. Twenty-eight of the 49 studies (57.1%) reported inclusion of productivity losses/gains as contributing to more favourable cost-effectiveness outcomes and ICERs, while 12 (24.5%) reported no substantial impact. On the basis of a multivariate analysis, rheumatoid arthritis as the target disease had a statistically significant association with the inclusion of productivity loss compared with psoriasis and inflammatory bowel disease.The results of our review suggest that incorporating productivity cost elements may positively affect cost-effectiveness outcomes in evaluations of therapeutics for immune-mediated disorders. Our work highlights the continued need for clarity when reporting how CEAs and CUAs in this disease area are conducted, in order to better inform healthcare decision-making.

Psoriasis is an inflammatory, chronic and immune-mediated disease that can affect the skin and joints. Pro-inflammatory cytokines have a dominant role in the pathogenesis of this heterogeneous disease in which the IL-23/IL-17 axis plays a crucial role. The IL-17 family is involved in numerous processes such as immune defense, intestinal disorders and diseases of the central nervous system. In psoriasis, in particular, many cytokines belonging to the IL-17 family are involved in the inflammatory cascade underlying the disease.The knowledge of the mechanisms and pathways behind psoriasis is crucial for the development of new target therapies. We focused on IL-17 biology in order to understand why biological drugs against this cytokine are an effective treatment for moderate to severe psoriasis. Clinical trials results of ixekizumab, brodalumab, secukinumab and bimekizumab have been presented.Il-17 inhibitors are a very fast and effective treatment against psoriasis; however, fungal infections can occur during their use, due to IL-17 biological functions. Therefore, it should be mandatory to choose the right patients to treat with these monoclonal antibodies in order to have a tailored target therapy for each patient.

Introduction: Since Anti-IL-17s availability, concerns about their safety have been raised due to the inhibition of physiological activities that IL-17A plays in the immune response against infections. Ixekizumab is a humanized monoclonal antibody specifically targeting IL-17A approved for the treatment of moderate-to-severe psoriasis. Areas covered: The aim of this review is to evaluate the safety profile of ixekizumab in moderate to severe psoriasis patients. A compressive literature review included article since March 2022. Expert opinion: in our analysis, most of the reported AEs were mild or moderate and rarely required treatment discontinuation. Among the class specific AEs to consider during ixekizumab treatment, there are the risk of Candida spp infections and the risk of IBD, which both were reported more frequently than if compared with placebo or other biologics (etanercept, ustekinumab, guselkumab). However, the reported candidiasis resulted mild-to moderate, and easily managed. The risk of IBD (both exacerbation and de novo diagnosis) represents a class effect of IL-17 inhibitors, which should be well evaluated before considering starting ixekizumab treatment. the most common AEs were represented by nasopharyngitis, upper respiratory tract infection, and injection-site reactions. The analysed studies confirmed the favourable safety profile of ixekizumab even in more recently published studies.

Psoriatic arthritis (PsA), is a complex inflammatory arthropathy with a heterogenous spectrum of disease presentation. Despite the vast therapeutic armamentarium, disease control in a considerable proportion of patients is suboptimal. The aim of this study was to assess the safety and efficacy of Janus kinase inhibitors (JAKi), in the management of key clinical domains of PsA including peripheral arthritis, psoriasis, enthesitis and dactylitis.Randomized placebo-controlled trials (RCTs) of JAKi in PsA were identified by a systematic literature search using EMBASE, PubMed and CENTRAL. All included studies underwent meta-analysis.A total of 5 RCTs were included. Patients were randomized to tofacitinib (n = 474), filgotinib (n = 65), upadacitinib (n = 1281) or placebo (n = 937). JAKi treatment was associated with superior efficacy across all primary outcome measures vs placebo: American College of Rheumatology (ACR) 20 (risk ratio [RR] 2.10, [95% CI 1.86-2.37], P .00001, I2 = 19%); ACR 50 (RR 3.43, [95% CI 2.37-4.96], P .00001, I2 = 66%); ACR 70 (RR 4.57, [95% CI 1.83-11.44], P = .001, I2 = 82%); Psoriasis Area and Severity Index 75 (RR 2.96, [95% CI 2.44-3.58], P .00001, I2 = 0%); enthesitis resolution (RR 1.82, [95% CI 1.56-2.12], P .00001, I2 = 0%); and dactylitis resolution (RR 1.85, [95% CI 1.57-2.16], P .00001, I2 = 0%). JAKi were associated with an overall increased risk of adverse events (RR 1.14, [95% CI 1.07-1.21], P = .0001, I2 = 0%) with increased risk of infection (RR1.23, [95% CI 1.08-1.39], P = .001, I2 = 0%) vs placebo.This pooled analysis demonstrates the efficacy of JAKi in treating key clinical domains of PsA. However, they are associated with an increased risk of adverse events, including infection. Further studies are required to corroborate these findings and further elucidate the safety profile.

The cross-talk between hyperproliferative keratinocytes and activated immune cells is responsible for the progression of psoriasis. The strategy to alleviate psoriasis through inhibiting the abnormal proliferation of keratinocytes remains challenging due to limited therapeutic effects and low skin penetration of drugs. Herein we designed an ultrasound-triggered phase-transition nanodroplet that could produce cavitation to enhance skin penetration and effectively generate reactive oxygen species (ROS) to induce keratinocyte apoptosis for psoriasis treatment. After ultrasound stimulation, the perfluoro-n-pentane (PFP) liquid core of the nanodroplets vaporized, and the Haematoporphyrin monomethyl ether (HMME) encapsulated in the nanodroplets generated plenty of intracellular ROS which caused the apoptosis of HaCat cells through inducing mitochondrial dysfunction. In addition, the blank nanodroplets successfully inhibited the secretion of IL-6 and TNF-α from macrophages and dendritic cells in vitro due to the anti-inflammatory effect of POPG. For the skin penetration test, the phase-transition nanodroplets could effectively accumulate in the epidermis of the skin and generate intracellular ROS. The in-vivo anti-psoriasis experiment demonstrated that the phase-transition nanodroplets relieved the symptoms of psoriasis lesion and inhibited epidermal hyperplasia through induction of cell apoptosis under ultrasound irritation. Meanwhile, the inflammatory cytokines in the skin lesion almost decreased to the normal baseline level after SDT. Collectively, this study demonstrated a new strategy to inhibit keratinocyte hyperproliferation for psoriasis management based on sonodynamic responded nanodroplets.

Background Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice. Objectives To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community. Methods A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any prespecified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways. Results Of 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n = 145) or psoriatic arthritis (n = 30). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors. The following candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, interleukin (IL)23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and kallikrein 8 (proteomic), tyramine (metabolomic); psoriatic arthritis: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, integrin b5, matrix metalloproteinase-3 and macrophage-colony stimulating factor (proteomic) and tyramine and mucic acid (metabolomic); and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation. Conclusions This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified herein to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? The current treatment paradigm in psoriasis is reactive.There is a need to develop effective risk-stratified management approaches that can proactively attenuate the substantial burden of disease.Prognostic biomarkers of disease progression have therefore been the focus of intense research. What does this study add? This review is the first to scope, collate and catalogue research investigating biomarkers of disease progression in psoriasis.The review identifies potentially promising candidate biomarkers for further investigation and highlights common important limitations that should be considered when designing and conducting future studies in this area.

Dupilumab, an IL-4/IL-13 receptor blocker, has been linked to emergent seronegative inflammatory arthritis and psoriasis that form part of the spondyloarthropathy spectrum. We systematically investigated patterns of immune disorders, including predominantly T helper 17‒(spondyloarthropathy pattern) and T helper 2‒mediated disorders and humoral autoimmune pattern diseases, using VigiBase, the World Health Organization's global pharmacovigilance of adverse drug reactions. Several bioinformatics databases and repositories were mined to couple dupilumab-related immunopharmacovigilance with molecular cascades relevant to reported findings. A total of 37,848 dupilumab adverse drug reaction cases were reported, with skin, eye, and musculoskeletal systems most affected. Seronegative arthritis (OR = 9.61), psoriasis (OR = 1.48), enthesitis/enthesopathy (OR = 12.65), and iridocyclitis (OR = 3.77) were highly associated. However, ankylosing spondylitis and inflammatory bowel disease were not conclusively associated. Overall, classic polygenic humoral‒mediated autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus were not associated with dupilumab use. Pathway analysis identified several biological pathways potentially involved in dupilumab‒associated adverse drug reactions, including the fibroblast GF receptor (in particular, FGFR2) pathway. MicroRNAs analysis revealed the potential involvement of hsa-miR-21-5p and hsa-miR-335-5p. In conclusion, IL-4/IL-13 blockers are not unexpectedly protective against humoral autoimmune diseases but dynamically skew immune responses toward some IL-23/IL-17 cytokine pathway‒related diseases. IL-4/13 axis also plays a role in homeostatic tissue repair and we noted evidence for a link with ocular and arterial pathology.

Both psoriasis and periodontal diseases are characterized by an exaggerated immune response to the microbiota residing on epithelial surfaces. This study aimed to explore the associations between the severity of psoriasis and periodontal destruction in patients with psoriasis.Thirty-three patients diagnosed with psoriasis were referred from the dermatology clinic of National Taiwan University Hospital. Full-mouth periodontal examination was performed and saliva was collected after patients signed informed consent forms. The Psoriasis Area Severity Index (PASI) as well as clinical periodontal parameters including probing depth (PD), plaque index (PI), gingival index (GI), and clinical attachment level (CAL) were evaluated. Salivary cytokines including interleukin (IL)-1β, IL-12, IL-17, interferon-γ, and tumor necrosis factor (TNF)-α were tested with the Luminex Bio-Plex system. Anti-inflammatory medication, tobacco use, and underlying comorbidities were included in the analysis.Baseline PASI was significantly associated with PI. PASI at follow-up was positively correlated with CAL ≥ 4 mm (%) and saliva IL-1β levels. Psoriasis patients who used non-steroidal anti-inflammatory drugs or topical steroids had significantly lower GI, PD ≥ 4 mm (%), and saliva IL-1β and TNF-α levels. Moreover, a history of tobacco use was associated with higher PD ≥ 4 mm (%).PI, CAL, and salivary IL-1β were associated with PASI. Periodontal severity was associated with psoriasis involvement. Periodontal inflammation in psoriasis may be modified by anti-inflammatory medication and tobacco use. Additional large-scale longitudinal and mechanistic studies are needed.

More and more studies have shown that ferroptosis is closely related to the progression of various diseases, but the significance of ferroptosis in psoriasis is still rarely explored. The detection of plasma and psoriatic lesions found that the contents of MDA and ROS were significantly increased, while the contents of SOD and GSH were significantly decreased, and the trend of increase or decrease in patients with progressive psoriasis was more obvious. The expression of ACSL4, a key regulator of ferroptosis, was significantly increased in psoriatic lesions and further up-regulated in patients with progressive psoriasis. ACSL4 expression was positively correlated with PASI score and the expression levels of inflammatory cytokines (TNF-α, IL-6, IL-8 and IL-17a), and linear regression analysis showed that high expression of ACSL4 in psoriatic lesions was associated with higher PASI score. Both ferroptosis inducer Erastin and IFN-γ/TNF-α significantly induced ferroptosis, inhibited keratinocyte viability, promoted the accumulation of MDA, ROS and Fe

SDZ-ADL is a biosimilar of reference adalimumab. Here, the safety and effectiveness data of SDZ-ADL from the British Association of Dermatologists Biologic and Immuno-modulators Register (BADBIR) are reported. In the safety set, data of SDZ-ADL were compared with conventional systemics data. In the effectiveness set, the effectiveness and quality-of-life of patients treated with SDZ-ADL as a first-time biologic, or who switched from a previous biologic to SDZ-ADL, were assessed using the Psoriasis Activity Severity Index (PASI) and Dermatology Life Quality Index (DLQI), respectively. A total of 565 (incidence rate (IR) per 1000 person-years 29.1, 95% CI 26.8–31.6) serious infections and 48 (IR 2.5, 95% CI 1.8–3.3) myocardial infarction events were reported in the conventional systemics cohort compared with four (IR 31.5, 95% CI 8.6–80.7) and one (IR 7.9, 95% CI 0.2–43.9) in the biologic cohort, respectively. One patient (0.7% (1/136)) reported injection-site pain in the biologic cohort. At 12 months, PASI ≤ 2 was achieved in 84.6% (11/13) and 76.9% (10/13) and DLQI 0/1 was achieved in 70% (7/10) and 75% (3/4) of patients in the biologic-naïve and biologic-switch cohorts, respectively. After one year of therapy, 82.7% (110/133) patients remained on SDZ-ADL. SDZ-ADL was well-tolerated and effective in patients with psoriasis.

Objective To investigate the incidence of and factors associated with SARS-CoV-2 testing and infection in immune mediated inflammatory diseases (IMIDs) versus matched non-IMIDs comparators from the general population. Methods We conducted a population-based, matched cohort study among adult residents from Ontario, Canada, from January to December 2020. We created cohorts for the following IMIDs: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis, systemic autoimmune rheumatic diseases, multiple sclerosis (MS), iritis, inflammatory bowel disease (IBD), polymyalgia rheumatica and vasculitis. Each patient was matched with five patients without IMIDs based on socio-demographic factors. We estimated the incidence of SARS-CoV-2 testing and infection in IMIDs and non-IMIDs patients. Multivariable logistic regressions assessed odds of SARS-CoV-2 infection. Results We studied 493,499 patients with IMIDs and 2,466,946 patients without IMIDs. Patients with IMIDs were more likely to have at least one SARS-CoV-2 test, versus patients without IMIDs (27.4% vs. 22.7%), but the proportion testing positive for SARS-CoV-2 was identical (0.9% in both groups). Overall, IMIDs patients had 20% higher odds of being tested for SARS-CoV-2 (odds ratio (OR) 1.20, 95% CI 1.19, 1.21). The odds of SARS-CoV-2 infection varied across IMIDs groups but was not significantly elevated for most IMID groups compared with non-IMIDs. The odds of SARS-CoV-2 infection was lower in IBD and MS and marginally higher in RA and iritis. Conclusions Patients across all IMIDs were more likely to be tested for SARS-CoV-2 versus those without IMIDs. The risk of SARS-CoV-2 infection varied across disease sub-groups.