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Stabilin‐1 (Stab1) and Stabilin‐2 (Stab2) are scavenger receptors expressed by liver sinusoidal endothelial cells (LSECs). The Stabilin‐mediated scavenging function is responsible for regulating the molecular composition of circulating blood in mammals. Stab1 and Stab2 have been shown to influence fibrosis in liver and kidneys and to modulate inflammation in atherosclerosis. In this context, circulating and localized TGFBi and POSTN are differentially controlled by the Stabilins as their receptors. To assess Stab1 and Stab2 functions in inflammatory and fibrotic skin disease, topical Imiquimod (IMQ) was used to induce psoriasis‐like skin lesions in mice and Bleomycin (BLM) was applied subcutaneously to induce scleroderma‐like effects in the skin. The topical treatment with IMQ, as expected, led to psoriasis‐like changes in the skin of mice, including increased epidermal thickness and significant weight loss. Clinical severity was reduced in Stab2‐deficient compared to Stab1‐deficient mice. We did not observe differential effects in the skin of Stabilin‐deficient mice after bleomycin injection. Interestingly, treatment with IMQ led to a significant increase of Stabilin ligand TGFBi plasma levels in Stab2−/− mice, treatment with BLM resulted in a significant decrease in TGFBi levels in Stab1−/− mice. Overall, Stab1 and Stab2 deficiency resulted in minor alterations of the disease phenotypes accompanied by alterations of circulating ligands in the blood in response to the disease models. Stabilin‐mediated clearance of TGFBi was altered in these disease processes. Taken together our results suggest that Stabilin deficiency‐associated plasma alterations may interfere with preclinical disease severity and treatment responses in patients.

Abstract This retrospective case series examines the efficacy and safety of Bimekizumab in 22 patients with moderate to severe plaque psoriasis in a real‐world clinical setting. The demographic and clinical characteristics of the participants, including a mean age of 43.7 years and a gender distribution of 60% male and 40% female, are summarised. Notably, 70% of the patients had previously received systemic therapy, and 50% had concurrent psoriatic arthritis. The evaluation over a 12‐week treatment period revealed a significant reduction in psoriasis area and severity index scores from a baseline mean of 11.5−1.0 at Week 4 and further down to 0.3 by Week 12. Similar improvements were observed in body surface area, physician's global assessment and dermatology life quality index scores. Bimekizumab was well‐tolerated with no reported adverse events, leading to no treatment discontinuations. These findings highlight the potential of Bimekizumab to provide rapid and sustained improvements in patients with moderate to severe plaque psoriasis, underlining its value in clinical practice.

Abstract Sarcoidosis is a multisystem disorder characterised by granulomatous inflammation affecting various organs. The skin is commonly involved and can serve as an initial indicator of disease. While the precise aetiology of sarcoidosis remains elusive, evidence suggests involvement of T‐helper type (TH)‐1 and TH‐17 pathways. Psoriasis shares common inflammatory pathways with sarcoidosis, prompting the repurposing of biologic therapies approved for psoriasis for off‐label treatment of cutaneous sarcoidosis. However, this approach has raised concerns due to the development of granulomatous eruptions in some patients. We present a case of a patient with psoriasis who was diagnosed with systemic sarcoidosis while on ustekinumab. We review previous cases of ustekinumab‐associated sarcoidosis and discuss the challenges associated with utilising biologic agents originally intended for psoriasis treatment for sarcoidosis.

Abstract A 43‐year‐old patient from Liberia presented with itching scaly plaques, impaired quality of life persisting for 9 months and intermittent joint pain in the knees. Personal and family history was unremarkable. Coexisting diagnoses included type 1 diabetes mellitus and liver cirrhosis due to chronic hepatitis B and D. The patient reported ongoing use of Tenofovir, Propranolol, Glargine and Aspart. Clinical examination showed disseminated brownish, partly confluent hyperkeratotic plaques distributed throughout the integument in a Fitzpatrick skin type V. A skin biopsy revealed histologically a psoriasiform dermatitis. Laboratory findings included lymphocytopenia and elevated liver values. Hepatitis B serology confirmed chronic hepatitis B. Considering the clinical and histopathological findings Psoriasis vulgaris was diagnosed and psoriatic arthritis was ruled out by a rheumatologist. After consulting with the hepatologist, systemic therapy with Apremilast was initiated. Despite an initial positive response, gastrointestinal side effects led to a switch to therapy with Tildrakizumab, with regular monitoring of transaminases and HBV DNA. Despite an initial positive treatment response, a secondary loss of efficacy occurred prompting a switch to Risankizumab. Psoriasis is a chronic inflammatory systemic disease significantly impacting quality of life, necessitating optimal long‐term management. In this case, therapy with Apremilast and biologic therapy targeting IL‐23 blockade, even with concurrent hepatitis B, was well tolerated and effective. However, the evidence on the safety of modern psoriasis therapies in known chronic infections remains limited. Noteworthy in this case report is the patient's dark skin type. Diagnosing inflammatory dermatoses in People of Colour is challenging due to less visible erythema and other clinical nuances, exacerbating the already poorer healthcare for People of Colour. This case aims to raise awareness about the need for increased representation of People of Colour in education, presentations and clinical trials to ensure better care for this patient population.

Abstract Background Psoriasis, a common chronic inflammatory skin disease with major impact on quality of life, is associated with several comorbidities. A better understanding of the pathogenesis of psoriasis has led to the development and approval of new therapeutic strategies such as biologics of different classes (targeting tumour necrosis factor‐α, interleukin (IL) 17 and IL12/23), phosphodiesterase‐4 inhibitors, and janus kinase inhibitors. Objectives The objective of this project was to investigate the evolution of baseline patient characteristics, disease characteristics and outcomes in Phase 3 trials. We hypothesized that the uptake of more effective drugs in the management of patients is reflected in the patient profile considered eligible for clinical trials. Methods A search in PubMed for Phase 3 trials of biologics, apremilast and deucravacitinib was performed. Forty trials were included and divided into five periods. The first three periods correspond with the chronological development of biologics, Period 4 contains trials of apremilast and Period 5 of deucravacitinib. For each trial, demographics and outcomes were extracted and mean values per period were calculated. Statistical analysis was performed in the biologics group and in the oral therapies group. Results Between Periods 1, 2 and 3: the mean percentage of patients with prior phototherapy (p

Abstract Poor adherence to therapies in dermatology remains a prevalent issue associated with treatment failure, poor clinical outcomes, and reduced quality of life. The aim of this review is to summarize the current literature on medical adherence specifically in dermatology, including ways to measure treatment adherence, factors contributing to nonadherence, interventions to increase adherence, and the impact of adherence on patient outcomes. We conducted a MEDLINE search between the years 2006 and 2023 using the following term: [adherence AND dermatology AND treatment]. The search was limited to English article types: clinical study, clinical trial, observational study, and randomized controlled trials in human subjects. The literature search yielded 323 articles. 52 of these articles met the inclusion criteria and were reviewed to define, measure, understand, and suggest means to increase adherence in dermatology. Additional articles were added from in text citations. Adherence can be measured using subjective and objective methods. Patient‐, treatment‐, and disease‐centered factors are important to consider when prescribing medications and implementing interventions to increase adherence. Reducing treatment adverse reactions, simplifying treatment regimens, and eHealth, education, communication, and psychological interventions are associated with improved adherence and disease outcomes. Understanding and enhancing adherence is crucial because of its impact on costs, treatment efficacy, and healthcare outcomes.

Abstract Background Dermatological diseases may cause significantly impaired quality of life, however patient reported outcomes are often disease specific, and not comparable across diseases. Objectives To examine daily time trade‐off (dTTO), as a measure of disease burden. Methods An epidemiological study based on patient data from Danish Skin Cohort (prospective cohort of Danish dermatology patients) was conducted. Data were linked with routinely collected data from Statistics Denmark. We included adults with either alopecia areata (AA), atopic dermatitis (AD), hidradenitis suppurative (HS), psoriasis, or rosacea. All patients with a diagnostic code listed above were invited to participate. The primary outcome was defined as a dTTO of more than 30 minutes daily. Results A total of 680, 1605, 611, 1664, and 1698 adults with AA, AD, HS, psoriasis, and rosacea, respectively, were included. In multiple regression models, patients with AA were most likely to have a dTTO of more than 30 minutes, followed by patients with HS, AD, psoriasis and rosacea. A total of 33.7% (AA), 29.3% (HS), 14.6% (AD), 11.1% (psoriasis), and 9.0% (rosacea) of patients were willing to spend two hours or more per day. The dTTO correlated with disease severity and DLQI across disease groups. Conclusions Patients with AA, followed by HS were willing to spend most time on treatment, possibly reflecting unmet needs in these patient groups. Daily TTO correlated with perceived disease severity in all groups and may be a useful measure of dermatological disease burden.

Abstract Background Skin diseases can have a significant impact on the physical, psychological and social well‐being of patients. Quantification of the burden of chronic spontaneous urticaria (CSU) compared to other dermatological conditions is limited. Objectives To evaluate the comparative humanistic and economic burden of CSU, atopic dermatitis (AD), and psoriasis (PSO) in five European countries (EU5). Methods This cross‐sectional analysis compared data from adult respondents with a physician diagnosis of CSU, AD and PSO from the 2020 National Health and Wellness Survey in EU5 (France, Germany, Italy, Spain and the United Kingdom). Outcomes included Short Form (SF)‐12v2 [mental (MCS) and physical component (PCS) summary scores], SF‐6D, EQ‐5D, EQ‐Visual Analogue Scale (VAS), Dermatology Life Quality Index (DLQI), General Anxiety Disorder‐7 (GAD‐7), Patient Health Questionnaire‐9 (PHQ‐9), Work Productivity and Activity Impairment (WPAI) and healthcare resource utilization (HRU). Multivariable analyses comparing CSU to AD and PSO, respectively, were conducted for each outcome. Results This analysis included 379 CSU, 788 AD and 2,636 PSO patients. Adjusted MCS and PCS scores were lower among CSU patients than AD (MCS, p = 0.006; PCS, p

Abstract Objective The relationship between systemic immune‐inflammation index (SII) and psoriasis and its prognosis is not yet clear. In this study, the correlation between SII and psoriasis, psoriasis comorbidities, and all‐cause mortality was investigated based on the National Health and Nutrition Examination Survey (NHANES). Methods The study population was derived from five NHANES cycles: 2003–2006, 2009–2014, and survival follow‐up was as of December 31, 2019. The association between SII and psoriasis and its comorbidities was analyzed using weighted multivariate logistic regression models. Weighted COX regression was used to calculate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Restricted cubic spline, subgroup and sensitivity analyses were also used. Logarithmic conversion was performed on SII(log2SII) to reduce the impact of outliers. Results A total of 21,431 participants were included in this study. As a continuous variable, log2SII was significantly associated with psoriasis in the fully adjusted model [OR = 1.20(1.04–1.39), p = .01]. log2SII remained positively associated with psoriasis after excluding participants with a history of cancer or cardiovascular disease (CVD), or non‐Hispanic black participants. Among psoriasis patients, log2SII was significantly associated with metabolic syndrome (MetS) [OR = 1.68(1.19,2.38), p = .004] and all‐cause mortality [HR = 1.48(1.09,1.99), p = .01]. Similar results were consistently observed when SII was analyzed as a categorical variable (in quartiles). Conclusion This study suggested a positive association between SII and the prevalence of psoriasis. Among psoriasis patients, SII was positively correlated with MetS and all‐cause mortality.

Abstract Psoriasis is a chronic skin disease characterized by abnormal proliferation and inflammation of epidermal keratinocytes. Fibroblast growth factor 12 (FGF12) is implicated in the regulation of diverse cellular signals; however, its precise mechanism in psoriasis requires further investigation. In this study, high expression of FGF12 is observed in the epidermis of skin lesion in psoriasis patients and imiquimod (IMQ)‐induced psoriasis like‐dermatitis. Moreover, specific loss of FGF12 in keratinocytes in IMQ‐induced psoriasis model alleviates psoriasis‐like symptoms and reduces proliferation. In vitro RNA sequencing demonstrates that knockdown of FGF12 effectively arrests the cell cycle, inhibits cell proliferation, and predominantly regulates the p53 signaling pathway. Mechanistically, FGF12 is selectively bound to the RING domain of MDM2, thus partially inhibiting the binding of β‐Trcp to MDM2. This interaction inhibits β‐Trcp‐induced‐K48 ubiquitination degradation of MDM2, thereby suppressing the activity of the p53 signaling pathway, which results in excessive cell proliferation. Last, the alleviatory effect of FGF12 deficiency on psoriasis progression is reversed by p53 knockdown. In summary, these findings provide valuable insights into the mechanisms by which FGF12 suppresses p53 signaling in keratinocytes, exacerbating the development of psoriasis. This positive regulatory loop highlights the potential of FGF12 as a therapeutic target to manage psoriasis.

Abstract Background and Aim Psoriasis is a prevalent chronic inflammatory skin condition, and the Mediterranean diet is often recommended for its health benefits, particularly its ability to mitigate chronic inflammation. This study sought to examine the extent to which psoriasis patients adhere to the Mediterranean diet and to explore its correlation with the severity of their condition Methods Seventy‐one psoriasis patients and 71 age‐ and sex‐matched healthy controls were enrolled the study and filled a standard questionnaire of adherence to the Mediterranean diet. The relationship between disease severity and adherence to the diet was also dealt with. Results The Mediterranean diet adherence score in the psoriasis group (5.25 ± 1.64) was significantly lower than the control group (6.28 ± 2.10) (p = 0.004). In addition, the consumption of fruit and fish in psoriasis patients was significantly lower than the control group and the consumption of red meat was significantly higher in the patient group. No significant relationship was found between the severity of the disease and the score of adherence to the Mediterranean diet (p = 0.42). Conclusion A significant difference between the two groups of psoriasis and the control group following the Mediterranean diet might be indicative of the relationship between diet and psoriasis and the potential benefits of this type of diet due to its anti‐inflammatory properties.

Abstract Reconstructed epidermal equivalents (REEs) consist of two distinct cell layers – the stratum corneum (SC) and the keratinocyte layer (KL). The interplay of these layers is particularly crucial in pruritic inflammatory disorders, like psoriasis, where a defective SC barrier is associated with immune dysregulation. However, independent evaluation of the skin barrier function of the SC and KL in REEs is highly challenging because of the lack of quantitative methodologies that do not disrupt the counter layer. Here, a non‐invasive impedance spectroscopy technique is introduced for dissecting the distinct contributions of the SC and KL to overall skin barrier function without disrupting the structure. These findings, inferred from the impedance spectra, highlight the individual barrier resistances and maturation levels of each layer. Using an equivalent circuit model, a correlation between impedance parameters and specific skin layers, offering insights beyond traditional impedance methods that address full‐thickness skin only is established. This approach successfully detects subtle changes, such as increased paracellular permeability due to mild irritants and the characterization of an immature SC in psoriatic models. This research has significant implications, paving the way for detailed mechanistic investigations and fostering the development of therapies for skin irritation and inflammatory disorders.

Abstract Background Monoclonal antibodies (mAbs) directed against tumour necrosis factor alpha (TNF‐α) and interleukin (IL)‐17 and ‐23 represent the ultimate therapeutic strategy in treating psoriasis patients, but scientific literature still does not provide conclusive results regarding the possible influence of previous biological therapies on real‐life therapeutic response. Objectives The objective of our work was to investigate any putative difference in the achievement and maintenance of PASI 75, 90 and 100, as well as the probability to achieve absolute PASI ≤ 1 and ≤3, between 305 bio‐naïve and bio‐experienced patients treated with anti‐IL mAbs. Methods A comparison between previous biologic and clinical factors, including relative and absolute PASI, was carried out through chi square test. Survival curves for the achievement of PASI 75, 90 and 100 and their differences were evaluated, performing a multivariate analysis (confidence interval 95%; p

Abstract Background People with psoriasis live with other long‐term conditions (co‐morbidities) that affect their use of healthcare, but the scale of this is not well characterised. Objectives Estimate the concurrent prevalence of co‐morbidities known to affect the use of healthcare in people living with psoriasis in England. Methods A retrospective cohort study using linked data from the UK's Clinical Practice Research Datalink with Hospital Episode Statistics, Office for National Statistics mortality records, and Index of Multiple Deprivation 2010. A cohort of adults (≥18 years) with psoriasis was matched with a comparator cohort of individuals based on age, sex and registered general practice between April 2007 and December 2017. A predefined list of 21 co‐morbidities was selected from a published measure: the Cambridge Multimorbidity Index (CMI). Descriptive analysis describes prevalence with statistical tests (t tests; two‐sample proportions test) of difference for selected variables. Results The study cohort comprised 372,949 individuals (54,817 psoriasis; and 318,132 matched‐comparator). The calculated CMI general score was statistically higher at 0.54 (standard deviation: 0.9) for psoriasis compared with 0.39 (standard deviation: 0.75) for the matched comparator (t test; p

Abstract Steroid phobia, characterized by an irrational fear or avoidance of topical corticosteroids, poses a significant challenge to the effective treatment of various skin conditions, including atopic dermatitis (AD) and psoriasis. This issue has its roots in the introduction of topical corticosteroids in the 1950s and has been perpetuated by concerns regarding adverse effects and misinformation. International Dermatological Societies including the Japanese Dermatological Association have endeavored to address this problem by providing information and guidance to physicians and patients, resulting in a better understanding of appropriate steroid use and risk management. Despite these efforts, steroid phobia has not been fully resolved in the world, including in Japan.To shed light on potential solutions, this review explores the field of behavioral economics, which offers insights into human decision‐making processes and cognitive biases. Richard Thaler's concept of nudges emerges as a promising strategy for influencing patients' decision‐making regarding steroid treatments. However, the effectiveness of nudges may vary depending on the strength of an individual's concerns and fears. In cases where patients exhibit strong resistance to steroid use, alternative psychological techniques that establish trust and facilitate clear communication may be more beneficial.This review emphasizes the necessity of adopting a multifaceted approach that integrates principles from behavioral economics and employs complementary psychological strategies to address steroid phobia and enhance treatment adherence in affected patient populations. By combining these approaches, healthcare professionals can tackle the complex nature of steroid phobia and promote better treatment outcomes for patients with skin conditions.

Abstract Background Beta‐defensins (BDs) are antimicrobial peptides secreted upon epithelial injury. Both chemotactic and antimicrobial properties of BDs function as initial steps in host defence and prime the adaptive immune system in the body. Psoriasis, a chronic immune‐mediated inflammatory disease, has both visible cutaneous manifestations as well as known associations with higher incidence of cardiometabolic complications and vascular inflammation. Objectives We aimed to investigate the circulating expression of beta‐defensin‐2 (BD2) in psoriasis at baseline compared to control subjects, along with changes in BD2 levels following biologic treatment at 1 year. The contribution of BD2 to subclinical atherosclerosis is also assessed. In addition, we have sought to unravel signalling mechanisms linking inflammation with BD2 expression. Methods Multimodality imaging, as well as inflammatory biomarker assays, were performed in biological naïve psoriasis (n = 71) and non‐psoriasis (n = 53) subjects. A subset of psoriasis patients were followed for 1 year after biological intervention (antitumour necrosis factor‐α [TNF‐α], n = 30; anti‐interleukin17A [IL17A], n = 21). Measurements of circulating BD2 were completed by enzyme‐linked immunosorbent assay (ELISA). Using HaCaT‐transformed keratinocytes, expression of BD2 upon cytokine treatment was assessed by quantitative polymerase chain reaction and ELISA. Results Herein, we confirm that human circulating BD2 levels are associated with psoriasis, which attenuate upon biological interventions (anti‐TNF‐α, anti‐IL‐17A). A link between circulating BD2 and subclinical atherosclerosis markers was not observed. Furthermore, we demonstrate that IL‐17A‐driven BD2 expression occurs in a Phosphatidylinositol 3‐kinase (PI3‐kinase) and Rac1 GTPase‐dependent manner. Conclusions Our findings expand on the potential role of BD2 as a tractable biomarker in psoriasis patients and describe the role of an IL‐17A‐PI3‐kinase/Rac signalling axis in regulating BD2 levels in keratinocytes.

Key Clinical Message Scalp lesions associated with psoriasis and cutaneous leishmaniasis can be clinically indistinguishable, leading to misdiagnosis. Herein, we highlight a 70‐year‐old male initially misdiagnosed with psoriasis but subsequently confirmed to have cutaneous leishmaniasis. This emphasizes the importance of considering alternative diagnoses, especially in atypical presentations, to ensure accurate treatment.

Abstract Background Psoriasis refers to a highly prevalent and immunologically mediated dermatosis with considerable deterioration in life quality. Wogonin, a sort of flavonoid, has been mentioned to elicit protective activities in skin diseases. However, whether Wogonin is implicated in the treatment of psoriasis and its specific mechanisms are not fully understood. Aim The present work attempted to elaborate the role of Wogonin during the process of psoriasis and to concentrate on the associated action mechanism. Methods Cell counting kit‐8 (CCK‐8) method was initially applied to assay the viability of human keratinocyte HaCaT cells treated by varying concentrations of Wogonin. To mimic psoriasis in vitro, HaCaT cells were exposed to M5 cytokines. CCK‐8 and 5‐Ethynyl‐2′‐deoxyuridine assays were adopted for the measurement of cell proliferation. Inflammatory levels were examined with enzyme‐linked immunosorbent assay. Immunofluorescence staining tested nucleotide‐binding oligomerization domain (NOD)‐like receptor family pyrin domain containing 3 (NLRP3) and Caspase‐1 expressions. Western blot examined the protein expressions of proliferation‐, inflammation‐, pyroptosis‐associated factors, and NLRP3. Results Wogonin treatment antagonized the proliferation, inflammatory response, and NLRP3/caspase‐1/Gasdermin‐D (GSDMD)‐mediated pyroptosis in M5‐challenged HaCaT cells. Besides, NLRP3 elevation partially abrogated the effects of Wogonin on M5‐induced proliferation, inflammatory response, and NLRP3/caspase‐1/GSDMD‐mediated pyroptosis in HaCaT cells. Conclusion In a word, Wogonin might exert anti‐proliferation, anti‐inflammatory and anti‐pyroptosis activities in M5‐induced cell model of psoriasis and the blockade of NLRP3/Caspase‐1/GSDMD pathway might be recognized as a potential mechanism underlying the protective mechanism of Wogonin in psoriasis, suggesting Wogonin as a prospective anti‐psoriasis drug.

Abstract Cutaneous sympathetic nerve is a crucial part of neuropsychiatric factors contributing to skin immune response, but its role in the psoriasis pathogenesis remains unclear. It is found that cutaneous calcium/calmodulin‐dependent protein kinase II‐γ (CAMK2γ), expressed mainly in sympathetic nerves, is activated by stress and imiquimod in mouse skin. Camk2g‐deficient mice exhibits attenuated imiquimod‐induced psoriasis‐like manifestations and skin inflammation. CaMK2γ regulates dermal γδT‐cell interleukin‐17 production in imiquimod‐treated mice, dependent on norepinephrine production following cutaneous sympathetic nerve activation. Adrenoceptor β1, the primary skin norepinephrine receptor, colocalises with γδT cells. CaMK2γ aggravates psoriasiform inflammation via sympathetic nerve–norepinephrine–γδT cell–adrenoceptor β1–nuclear factor‐κB and –p38 axis activation. Application of alcaftadine, a small‐molecule CaMK2γ inhibitor, relieves imiquimod‐induced psoriasis‐like manifestations in mice. This study reveals the mechanisms of sympathetic‐nervous‐system regulation of γδT‐cell interleukin‐17 secretion, and provides insight into neuropsychiatric factors dictating psoriasis pathogenesis and new potential targets for clinical psoriasis treatment.

Abstract A 52‐year‐old woman presented with typical patches of psoriasis restricted to the lower limbs that had been saphenectomized 16 years before. Saphenectomy uniformly destroys the cellophane‐like walls of the major lymphatic vessel running adjacent to the saphenous vein, thus creating an obstacle to the local lymph drainage and changes in local immune response. The involved immunocompromised district may be more susceptible to develop immune‐related disorders.

Abstract Background Brodalumab, a fully human anti‐interleukin (IL)‐17 monoclonal antibody that blocks IL‐17RA, is approved in Europe for the treatment of adult patients with moderate‐to‐severe plaque psoriasis who are candidates for systemic treatment. Objectives This study evaluated the achievement and maintenance of therapeutic response for 1 year in psoriasis patients treated with brodalumab in the Italian clinical practice. Methods Real‐world, multicenter, observational, retrospective and prospective study. The retrospective phase ranged from enrolment visit to initiation of brodalumab (12 ± 4 weeks before). The prospective phase ranged from enrolment to a routine follow‐up visit set after 52 ± 4 weeks. Results One hundred eighty‐four patients were eligible and 164 completed the observation period (median 11.9 months; Q1–Q3: 11.4–12.3). At enrolment, the mean duration of disease was 13.9 years (standard deviation; 13.3), 94% of patients (N = 172) had ≥1 clinical manifestation of psoriasis, mainly erythema and itching, and 95.6% had received ≥1 antipsoriatic treatment before brodalumab. Patients who reached an absolute Psoriasis Area and Severity Index (PASI) score ≤3 at week 12 and maintained it ≤3 through week 52 were 97 (64.7%). At week 12, 72.7% of patients achieved PASI 75, 54.5% PASI 90 and 42.0% PASI 100. At Week 52, 92.9% of patients achieved PASI 75, 84.4% PASI 90 and 61.7% PASI 100. A static Physician's Global Assessment (sPGA) score = 0 was obtained by 55.0% of patients after 12 weeks of brodalumab and by 77.0% after 52 weeks. A Dermatology Life Quality Index ≤1 was reported by 71.9% of patients after 12 weeks and by 89.9% after 52 weeks of treatment. No significant outcome differences were shown among patient subgroups defined by previous antipsoriatic treatments (none, systemic other than biologics or biologic) at either brodalumab initiation or any of the subsequent study visits. Conclusions In this real‐world setting, brodalumab was rapidly effective on skin lesions and quality of life both in biologic‐naïve and biologic‐experienced moderate‐to‐severe psoriasis patients, with a favourable safety profile.

Abstract Background Some patients treated with biologic therapy for psoriasis experience adverse events causing treatment discontinuation. Objectives To identify predictors of adverse events resulting in discontinuation of biologics for psoriasis. Methods This cohort study involved data from the Danish nationwide registry DERMBIO. A classification algorithm based on gradient‐boosted decision trees combined with a mixed‐effects model was applied to data on various drugs to predict treatment discontinuation caused by adverse events and to identify important predictors. Results This study comprised 4876 treatment series, including 3078 (63.1%) that were discontinued. With adverse events causing 19.6% of these, it was the second most frequent reason for discontinuation following ineffectiveness. The proportion of treatments discontinued due to adverse events was 20.0% [16.7%, 23.9%; 95% confidence interval (CI)] among patients that had discontinued their previous treatment series due to adverse events, and 11.6% [10.3%, 13.1%; 95% CI] among treatment series where the previous treatment was discontinued due to other reasons (p

Abstract Background The treatment expectations of patients with psoriasis are essential for clinical outcomes. Objectives To examine disease‐ and treatment related intra‐ and interpersonal factors and their relation to treatment expectations among patients with psoriasis who initiate or switch biological therapy. Methods Consecutive adult patients with moderate to severe psoriasis who initiated or switched biological therapy completed a questionnaire regarding their disease‐ and treatment‐related expectations. Additionally, they filled out Patients' Attitudes and Beliefs Scale (PABS), Trust in Physician Scale (TPS) and Dermatology Life Quality Index (DLQI) questionnaires. Psoriasis Area Severity Index (PASI) was scored before and 3 months after treatment initiation. Results A total of 65 patients participated; 28% expected

Abstract Background Tildrakizumab is an interleukin‐23p19 inhibitor approved for the treatment of moderate‐to‐severe plaque psoriasis. The new Dermatology Life Quality Index (DLQI)‐Relevant (DLQI‐R) scoring system avoids the bias in the not relevant response option of the DLQI by adjusting the total score to the relevant items. Objectives To assess the impact of tildrakizumab on health‐related quality of life (HRQoL) in patients with moderate‐to‐severe psoriasis in the reSURFACE 2 phase 3 trial as measured with the original DLQI scoring and with the new DLQI‐R. Methods Post hoc analysis of adult patients with moderate‐to‐severe plaque psoriasis from a double‐blinded, randomized, controlled, 52‐week trial. The presented analysis is based on observed cases. Results At baseline, 31.9%/33.6%/40.0% of patients on tildrakizumab 100 mg/tildrakizumab 200 mg/placebo had ≥1 DLQI item marked as ‘not relevant’. The most frequently ‘not relevant’ items were ‘sport’ (14.0%/13.9%/15.5%) and ‘working/studying’ (13.4%/11.3%/12.9%), in the tildrakizumab 100 mg/tildrakizumab 200 mg/placebo groups, respectively. At baseline, 68.1%/73.0%, 60.3%/63.2% and 62.6%/65.8% of patients on tildrakizumab 100 mg, tildrakizumab 200 mg and placebo had a DLQI > 10/DLQI‐R > 10, respectively. Mean DLQI/DLQI‐R scores at baseline were 14.8/15.5, 13.3/14.1, and 14.1/15.0 in the tildrakizumab 100 mg, tildrakizumab 200 mg and placebo groups, respectively. The median change from baseline in both DLQI and DLQI‐R scores at Week 12 was greater in the tildrakizumab 100 mg and 200 mg groups versus placebo (−10.0, −9.0, −1.0 and −11.0, −9.3, −1.1, respectively). At Week 52, the median change from baseline in DLQI/DLQI‐R was −13.0/−14.0 and −10.0/−10.1 in the tildrakizumab 100 mg and 200 mg groups, respectively. Conclusions Treatment with tildrakizumab resulted in significant and sustained improvements in HRQoL up to Week 52 in patients with moderate‐to‐severe psoriasis. The DLQI‐R provides a more unbiased HRQoL assessment ensuring that those who are unable to work/partake in sport have a truer assessment and opportunity for treatment.

Abstract Ocrelizumab (OCR) is a humanized anti‐CD20 monoclonal antibody approved for treating multiple sclerosis. We present three patients who developed psoriasiform dermatitis (PsD) during OCR treatment and a review of the cases published to date. We hereby report the first exclusive fingernail involvement. Most of the cases had a mild skin involvement and only one case required OCR discontinuation. No association with arthritis, personal or family history of psoriasis was found. Data compiled suggests that PsD tends to appear within the first year of treatment. There are few studies focusing on B‐lymphocytes in psoriasis and several hypotheses attempt to explain their role. The most widely accepted is the depletion of regulatory B‐lymphocytes with immunomodulatory function through interleukin‐10. However, the exact mechanism by which this occurs with OCR remains unclear and the presented case of anti‐CD20‐induced PsD highlights the importance of continuous monitoring of new treatments in terms of dermatological side effects and the induction of skin diseases, in particular psoriasis. There is also a need to inform the professional community about the possibility of psoriasis in patients with multiple sclerosis and the consequences of this condition.

Abstract Introduction Mucosa‐associated lymphoid tissue 1 (MALT1) modulates T helper cell differentiation, pro‐inflammatory cytokine production, and epidermal hyperplasia to participate in the pathology of psoriasis. This study aimed to explore the correlation of blood MALT1 with treatment outcomes in psoriasis patients. Methods MALT1 was detected in peripheral blood mononuclear cells by reverse transcription‐quantitative polymerase chain reaction in 210 psoriasis patients before starting or converting to a new therapy, 50 disease controls, and 50 healthy controls. The psoriasis area severity index (PASI) score was evaluated at month (M)1, M3, and M6 in psoriasis patients. Results MALT1 was increased in psoriasis patients versus disease controls and healthy controls (both p

Key Clinical Message Bicipitoradial bursitis is an unusual cause of cubital fossa pain in PsA patients. Bedside Ultrasound is a valuable tool to correlate the source of pain in rheumatic and musculoskeletal diseases.

Background Increasing evidence suggests a higher propensity for acute myocardial infarction (MI) in patients with psoriasis. However, the shared mechanisms underlying this comorbidity in these patients remain unclear. This study aimed to explore the shared genetic features of psoriasis and MI and to identify potential biomarkers indicating their coexistence. Methods and Results Data sets obtained from the gene expression omnibus were examined using a weighted gene coexpression network analysis approach. Hub genes were identified using coexpression modules and validated in other data sets and through in vitro cellular experiments. Bioinformatics tools, including the Human microRNA Disease Database, StarBase, and miRNet databases, were used to construct a ceRNA network and predict potential regulatory mechanisms. By applying weighted gene coexpression network analysis, we identified 2 distinct modules that were significant for both MI and psoriasis. Inflammatory and immune pathways were highlighted by gene ontology enrichment analysis of the overlapping genes. Three pivotal genes—Src homology and collagen 1, disruptor of telomeric silencing 1‐like, and feline leukemia virus subgroup C cellular receptor family member 2—were identified as potential biomarkers. We constructed a ceRNA network that suggested the upstream regulatory roles of these genes in the coexistence of psoriasis and MI. Conclusions As potential therapeutic targets, Src homology and collagen 1, feline leukemia virus subgroup C cellular receptor family member 2, and disruptor of telomeric silencing 1‐like provide novel insights into the shared genetic features between psoriasis and MI. This study paves the way for future studies focusing on the prevention of MI in patients with psoriasis.

Key Clinical Message Rituximab which is established as a main treatment for pemphigus vulgaris can be a potential causative factor for development of psoriasis in some patients. It is preferred to avoid using rituximab in patients who had a history of psoriasis. Acquainting medical doctors about rituximab‐related cutaneous complications will help them in detection and management. Abstract Rituximab is a human/murine monoclonal antibody targeting the CD20 antigen on B‐lymphocytes surface. Although it is used as promising treatment for pemphigus, nowadays it is also a new therapy for other autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, and others like non‐Hodgkin's lymphoma. Although there is increasing evidence regarding the safety and effectiveness of rituximab in these diseases, many cutaneous adverse effects have been reported. Here, we describe a 48‐years‐old patient affected with pemphigus vulgaris who developed psoriatic lesions on her on scalp, trunk, and extremities, 4 months after the second course of rituximab.

Atopic dermatitis (AD) and psoriasis are among the most common chronic inflammatory skin diseases. Although AD and psoriasis are distinguished using clinical criteria, the lesions of these two diseases are sometimes highly similar, making diagnosis difficult. In addition, the mechanisms underlying these two diseases are not fully clear. Here, we aimed to identify potential genes and regulatory mechanisms in AD and psoriasis patients to aid in the diagnosis and treatment of AD and psoriasis. The GSE121212 dataset was obtained from the NCBI Gene Expression Omnibus database and weighted gene co‐expression network analysis (WGCNA) was applied. The functions of genes in modules of interest were determined using Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis with the ggplot2 package of r. The hub genes were obtained using the Search Tool for the Retrieval of Interacting Genes database and then visualized using cytoscape. The MEgreen and MEbrown modules were identified to associate with AD and psoriasis, respectively, and the biological functions and pathways of genes in clinically significant modules were detected and analyzed. Hub genes in these two modules and details on potential protein interactions were also revealed. The genes and modules identified by WGCNA might contribute to our understanding of the molecular mechanisms of AD and psoriasis and aid in their diagnosis and treatment.

Abstract Psoriasis can affect diverse facets of patients' lives over time and may lead to irreversible cumulative life course impairment (CLCI). The CLCI concept initially described in 2010 in the context of psoriasis encompasses the intricate interaction between physical, psychological, social and economic burden and is influenced by several factors such as coping mechanisms, personality and external factors. CLCI assessment is conducted to characterise and ultimately mitigate or prevent the patient's burden over the life course. This review aims to give a comprehensive overview of the development and use of the CLCI concept in psoriasis since its inception. A narrative literature review was conducted from 2010 to 2022 and included 19 publications. As original studies on CLCI are scarce, this review primarily relied on case studies and those without longitudinal assessment. The core components of CLCI burden identified in patients' narratives include physical impairment, psychological impairment, stigma, socioeconomic burden and modulating factors. Modulating factors are crucial to mitigate the burden but are not equally explored. The burden associated with psoriasis stands across all dimensions covered by CLCI, thus confirming its suitability in clinical management and future studies. A better understanding of CLCI can support physicians and researchers in improving patients' lives and raising awareness on the necessity to develop early, efficient and patient‐centric interventions. The practical and systematic adoption of CLCI yet relies on the development and psychometric validation of a questionnaire that measures it.

Abstract Background Psoriasis is an immune‐mediated polygenic skin disorder. It is influenced by multiple genes as well as environmental factors including infection and trauma. Psoriasis is associated with molecular biomarkers such as HLA‐C*06:02 and associated single‐nucleotide variants (SNVs). Furthermore, the circulatory cytokines, interleukin (IL)‐17 and IL‐23 are elevated in psoriasis patients. Objectives To investigate the incidence of biomarkers namely, HLA‐C*06:02, SNV's (rs30187, rs27044, rs2248374), and IL17 and IL23 as possible diagnostic/prognostic biomarkers of value, individually or in combination in psoriasis patients. Methods These biomarkers, HLA‐C*06:02, SNV's (rs3018, rs27044, rs2248374), and IL17 and IL23 (and their ratio) were tested in a cohort of 40 psoriasis patients attending a dermatology clinic situated in a tertiary academic hospital as well as 40 healthy controls by: HLA typing using sequence‐specific primers (PCR SSP), real time PCR, and Luminex technology, respectively. Results HLA‐C*06:02 was significantly elevated in our patient cohort with 53% (n = 21) of psoriasis patients expressing the HLA‐C*06:02 allele versus 15% (n = 6), p = 0.001 in the healthy controls. Both IL‐17 and IL‐23 were significantly elevated in the psoriasis patients compared to the normal controls (p = 0.0001 and p = 0.0005, respectively). The SNV rs2248374 showed an association with both IL‐17 and HLA‐C*06:02 in patients with psoriasis. Conclusions Overall, these novel findings are the first to be published for South African and African populations in the public health sector. The finding of the current study corroborates international studies. Further validation through geographic and population expansion may assist in identifying individuals at risk of disease progression in psoriasis. These biomarkers may be used as potential prognosticators which will offer the opportunity for early medical intervention to reduce the burden of disease.

Abstract Background There is limited evidence over the real‐life secukinumab survival in psoriatic patients, especially in the long‐term bio‐naïve subjects, and to date biological treatments have been assessed in patients with a chronic and recalcitrant psoriasis. It has been hypothesised that early intensive treatment with biological therapies could decrease pathogenic tissue resident memory (TRm) cells migration and potentially modify the natural course of psoriasis and related comorbidities. Objectives To analyze long‐term secukinumab efficacy, safety and survival, and its predictive factors for psoriasis treatment determining also whether early intervention may result in better outcomes for patients. Methods Bio‐naïve psoriatic patients under treatment with secukinumab (n = 128 patients) in a daily practice setting were analyzed in a retrospective multicentric study and followed up to 8 years. Drug survival rate, efficacy, posology and safety were reported. Results The overall secukinumab survival was 81.9% for an average treatment exposure of 147.9 weeks. The approved posology was the most commonly prescribed regimen (78.7%), and 17.7% could be optimized. An absolut‐PASI ≤3 was reached by 86.6%, 82.6% and 91.7% at the weeks 48,156 and 264, respectively. The incidence of arthritis or psoriasis related comorbidities was low. The response was not influenced by weight, age (>65), gender or the presence of arthritis. No severe adverse events were reported. Conclusions In our bio‐naïve series, the high efficacy and long‐term survival rates observed and the low prevalence of arthritis and comorbidities might suggest that early intervention could contribute to modify the course of the disease, but further studies are needed.

Abstract Heat shock protein 90 (HSP90) is a chaperone protein belonging to the HSP family. HSP90 modulates clients by stabilising, folding, maturing, and tagging clients for proteasomal degradation. Several clients of HSP90 are involved in cancer development and HSP90 is required for some oncoproteins, making HSP90 a potential target in anticancer treatment. Recently HSP90 has also been suggested as a potential drug target in inflammatory skin diseases based on both in vitro and in vivo studies in animal models and human clinical trials. The role of HSP90 in blistering skin diseases has been studied in vitro, ex vivo, and in vivo using animal models. Human clinical studies investigating HSP90 inhibition in psoriasis and hidradenitis suppurativa have either been conducted or are ongoing and in vitro and ex vivo studies have investigated the role of HSP90 in systemic lupus erythematosus and diffuse cutaneous systemic sclerosis. Here, we review the current literature investigating the role of HSP90 in these diseases.

Abstract Background Treatment guidelines for psoriasis and psoriatic arthritis consider all skin and joint domains and recommend collaborative multidisciplinary team (MDT) working. The uptake of joint working in clinical practice for psoriatic disease management has not been well studied. Objectives This United Kingdom (UK) study aimed to provide a better understanding of current working patterns and collaborating specialities, as well as benefits and challenges of combined clinics. Methods An online survey was emailed to dermatology and rheumatology healthcare professionals (HCPs) using professional networks. Results Responses were received between October 2020 and April 2021 (N = 80); 60.0% of respondents worked in dermatology and 40.0% in rheumatology. Use of combined clinics with dermatology was reported by 40.6% of rheumatology HCPs, including joint (25.0%), parallel (3.1%) and virtual clinics (6.3%), and MDT meetings (6.2%). Similarly, 50.1% of dermatology HCPs reported use of joint (25.0%), parallel (4.2%) and virtual clinics (2.1%), single visits (2.1%), and MDT meetings (16.7%) with rheumatology. Around one‐quarter of respondents collaborated via email, which was also the main method of collaboration with other specialists. Overall, one‐quarter of respondents reported no collaboration in psoriatic disease management. Perceived benefits of combined clinics included shared knowledge, improved patient outcomes and increased patient satisfaction. Challenges included difficulties in aligning clinician time and geographical location, as well as limited ‘buy‐in’ from senior management. Most respondents felt that the COVID‐19 pandemic had partially or significantly impacted combined clinics. Conclusions This study is one of the first to survey collaborative working in psoriatic disease management and the first in the UK. These findings demonstrate the variety of approaches used and a lack of collaborative working by one‐quarter of respondents. Despite the benefits, numerous challenges in establishing formal arrangements exist. More evidence is needed to demonstrate improved patient outcomes with collaborative working and to standardise best practice.

Abstract Background The use of biologic agents has significantly improved the quality of life for patients with chronic skin diseases, and many other autoinflammatory diseases, over the past two decades. Due to the immunosuppressive nature of biologic agents, patients on these treatments are at increased risk of infection. Compulsory serological testing and vaccine optimisation before commencing biologic therapy is not common practice, potentially leaving some of these patients exposed to vaccine‐preventable disease. Objectives Our real‐world data aims to assess if the use of biologic agents in patients with hidradenitis suppurativa and psoriasis leads to an accelerated loss of immunity to diseases commonly vaccinated against. Methods We present 77 patients with psoriasis and hidradenitis who underwent serological testing before and after commencing biologic treatment. Statistical analysis, using the Z‐test for differences between two populations, was used to determine if a significant number of patients lost immunity after commencing biologic therapy for the treatment of their skin disease. Results A significant number of our patients lost immunity, especially to Hepatitis B (p

Abstract Background Biologicals are a widely used treatment for psoriasis (PsO), however, biologicals are expensive and while continuous use is warranted, sometimes need switching. In January 2021, dermatologists of Bravis Hospital and dermaTeam clinic actively switched 91 patients, who received Ixekizumab, to Brodalumab due to health economic reasons. This is a retrospective, real‐world cohort study. Objectives This study aimed to assess Brodalumab drug survival, reasons for discontinuing Brodalumab and side effects. The researchers also hoped to gain insight into determinants for Brodalumab drug survival. Methods Data were retrospectively extracted from electronic medical records (EMR). Psoriasis Area Severity Index (PASI) scores were evaluated. Drug survival was analysed using Kaplan–Meier estimates. Analyses were split according to the reason for discontinuing: primary or secondary ineffectiveness, and side effects. Results A total of 91 EMRs were included. Overall, 29 patients (32%) discontinued Brodalumab within 1 year owing to: primary inefficacy (45%), secondary inefficacy (31%), only side effects (14%), or other reasons (10%). The most reported side effect was xerosis cutis, followed by joint pain. PASI scores were lacking. No determinants to make switching more successful were found. Drug survival was 53% at Week 50. Conclusions Drug survival of Brodalumab after switch from Ixekizumab in our patient group was low at 53%. Inadequate disease control was more important than side effects.

Abstract Psoriasis is a chronic inflammatory skin disease that is associated with obesity and myocardial infarction. Obesity‐induced changes in lipid metabolism promote T helper 17 (Th17) cell differentiation, which in turn promotes chronic inflammation. Th17 cells have central roles in many inflammatory diseases, including psoriasis and atherosclerosis; however, whether treatment of obesity attenuates Th17 cells and chronic inflammatory diseases has been unknown. In this study, we found an increase in Th17 cells in a patient with obesity, type 2 diabetes and psoriasis. Furthermore, weight loss with diet and exercise resulted in a decrease in Th17 cells and improvement of psoriasis. This case supports the hypothesis that obesity leads to an increase in Th17 cells and chronic inflammation of the skin and blood vessel walls, thereby promoting psoriasis and atherosclerosis.

Abstract The interleukin‐23 (IL‐23)/IL‐17 immune axis has been linked to the pathology of psoriasis, but how this axis contributes to skin inflammation in this disease remains unclear. We measured inflammatory cytokines associated with the IL‐23/IL‐17 immune axis in the serum of patients with psoriasis using enzyme‐linked immunosorbent assays. Psoriasis was induced in male C57BL/6J mice using imiquimod (IMQ) cream, and animals received intraperitoneal injections of recombinant mouse anti‐IL‐23A or anti‐IL‐17A antibodies for 7 days. The potential effects of the IL‐23/IL‐17 immune axis on skin inflammation were assessed based on pathology scoring, hematoxylin–eosin staining of skin samples, and quantitation of inflammatory cytokines. Western blotting was used to evaluate levels of the following factors in skin: ACT1, TRAF6, TAK1, NF‐κB, and pNF‐κB. The serum of psoriasis patients showed elevated levels of several cytokines involved in the IL‐23/IL‐17 immune axis: IL‐2, IL‐4, IL‐8, IL‐12, IL‐17, IL‐22, IL‐23, and interferon‐γ. Levels of IL‐23p19 and IL‐17 were increased in serum and skin of IMQ‐treated mice, while ACT1, TRAF6, TAK1, NF‐κB, and pNF‐κB were upregulated in the skin. A large proportion of NF‐κB p65 localized in nucleus of involucrin+ cells in the epidermis and in F4/80+ cells of the dermis of psoriatic lesional skin. Treating these animals with anti‐IL‐23 or anti‐IL‐17 antibodies improved pathological score and immune imbalance, mitigated skin inflammation and downregulated ACT1, TRAF6, TAK1, NF‐κB, and pNF‐κB in skin. Our results suggest that skin inflammation mediated by the IL‐23/IL‐17 immune axis in psoriasis involves activation of the ACT1/TRAF6/TAK1/NF‐κB pathway in keratinocytes and macrophage.

Abstract Generalised pustular psoriasis is a rare, unpredictable, and sometimes severe subtype of psoriasis whose treatment is hampered by a lack of consensus and standardised therapeutic guidelines. The recent recognition of the involvement of the innate interleukin (IL)‐1/IL‐36 pathway has allowed the development of new biologic drugs such as Spesolimab. We present the case of a woman with persistent generalised pustular psoriasis (GGP) who, after numerous failures with several systemic and biologic therapies, was treated with Spesolimab and showed a very rapid and sustained response over time.

Abstract Background Psoriasis is an immune‐mediated chronic inflammatory skin disease, in which T helper 17 (Th17) cells and its effective cytokine interleukin (IL)‐17A play a pivotal pathogenic role. High mobility group box 1 (HMGB1) is an important proinflammatory cytokine, which has been confirmed to be highly expressed in the peripheral circulation and epidermis tissues of psoriasis patients. The regulatory effect of HMGB1 on IL‐17A expression and function has been reported in some inflammatory and autoimmune diseases by the HMGB1‐Toll‐like receptor 4 (TLR4)‐interleukin (IL)‐23‐IL‐17A pathway. While, in the pathological environment of psoriasis, whether HMGB1 can exert the regulatory effect on IL‐17A is not clear. Objective We aimed to evaluate the role of HMGB1‐TLR4‐IL‐23‐IL‐17A pathway in the pathogenesis of psoriasis and explore the possible regulatory mechanism of HMGB1 on Th17 cell differentiation. Methods Serum levels of HMGB1, TLR4, IL‐23, and IL‐17A were quantified in 50 patients with moderate‐to‐severe plaque psoriasis and 30 healthy controls. Peripheral blood mononuclear cells were acquired from 10 severe psoriasis patients and administrated by different concentrations of recombinant‐HMGB1 (rHMGB1) to detect the Th17 cell percentage, mRNA and protein levels of TLR4, IL‐23, IL‐17A and retinoid‐related orphan receptor γt (RORγt). Results The serum levels of HMGB1, TLR4, IL‐23, and IL‐17A in psoriasis patients were significantly higher than healthy controls, especially in severe patients, and positively correlated with the severity index. There were also positive correlations between every two detected indicators of HMGB1, TLR4, IL‐23, and IL‐17A. In vitro study, rHMGB1 can promote the elevated expression of Th17 cell percentage as well as TLR4, IL‐23, IL‐17A, and RORγt in a dose‐dependent manner. Conclusion HMGB1 can contribute to the pathogenesis of psoriasis by regulating Th17 cell differentiation through HMGB1‐TLR4‐IL‐23‐RORγt pathway, then promotes IL‐17A production and aggravates inflammation process. Targeting HMGB1 may be a possible potential candidate for the immunotherapy of psoriasis.

Abstract The transcription factor LIM‐only protein 4 (LMO4) is overexpressed in the psoriatic epidermis and regulates keratinocyte proliferation and differentiation. High LMO4 expression levels are induced by interleukin‐23 (IL‐23) to activate the AKT/STAT3 signaling pathway. Interleukin‐6 (IL‐6) is mainly involved in regulating T cell functions and development in patients with psoriasis. However, whether LMO4 expression is regulated by IL‐6 remains unclear. Therefore, the purpose of this study is to explore the role and molecular mechanisms of IL‐6 in regulating LMO4 expression. The interleukin‐6 (IL‐6) levels in human plasma were determined using a chemiluminescence immunoassay system. A psoriasis‐like mouse model was established using imiquimod induction. Epidermal keratinocytes (HaCaT) were cultured in defined keratinocyte‐serum‐free medium and stimulated by IL‐6 alone or with inhibitors. The proteins of interest were detected using western blot analysis, immunofluorescence, and immunohistochemistry. The 5‐ethynyl‐2′‐deoxyuridine assay was used to detect cell proliferation. The results revealed that IL‐6 levels were markedly increased in the plasma of patients with psoriasis, compared to healthy control. The high expression of LMO4 was consistent with high levels of IL‐6, p‐AKT, and p‐STAT3 in the lesions of both psoriasis patients and imiquimod‐induced psoriasis‐like mice. IL‐6 activates the AKT/STAT3 signaling pathway, followed by LMO4 high‐expression in HaCaT cells. IL‐6 induces HaCaT proliferation and differentiation via AKT/STAT3 signaling pathway activation. We think that the high expression of LMO4 in psoriatic keratinocytes requires IL‐6 to activate the AKT/STAT3 signaling pathway and leads to epidermal keratinocytes abnormal proliferation and differentiation.

Abstract During the past few decades, classical in‐person communication has been enriched by opportunities for telemedicine. We are in a learning healthcare environment that takes advantage of the opportunities of telemedicine and in‐person consultations, reconciling the individuality of the patient and his/her psoriasis. A working group of experts in telemedicine was installed by the International Psoriasis Council (IPC) to formulate the opportunities and limitations of telemedicine in the diagnosis and treatment of psoriasis. The working group formulated statements on various aspects of telemedicine according to the nominal group technique to reach a consensus on these statements and explore the variation of opinions. Thirty‐six statements regarding teledermatology and psoriasis were agreed upon by the IPC working group. The value and necessity for the implementation of teledermatology in dermatologic healthcare practices for psoriasis are essential. Management of psoriasis through teledermatology is feasible with a few exceptions. In this communication, the statements are presented and discussed in the context of the available literature, and finally, a call to action by IPC is formulated related to these statements.

Abstract Introduction Patients with psoriasis are at risk of depression, anxiety and adjustment disorder (DAAD). Randomized control trials reported improvement in depression and anxiety symptoms among patients with psoriasis receiving tumour necrosis factor inhibitors and ustekinumab (TNFi/UST) versus placebo and conventional systemic agents (CSA). The risk of DAAD among TNFi/UST versus CSA users was not assessed in real‐world settings. Objective To compare DAAD incidence among patients with psoriasis using CSA and subsequently received (vs. not) TNFi/UST. Methods We conducted a retrospective cohort study using the province of Quebec health administrative databases (1997–2015). Among adult patients with a diagnosis of psoriasis and initiating a CSA, we included those who later initiated a TNFi/UST, as a switch or add‐on, at the date of their first prescription fill (index‐date). We also included TNFi/UST nonusers at a date chosen to match the time between the first CSA and the index date of a random TNFi/UST user. TNFi/UST nonusers were classified into current or previous CSA users according to their last CSA received in the 90 days before or after their index date. Marginal structural Cox regression models weighted by the inverse probability of exposure compared the risk of DAAD between TNFi/UST, current and previous CSA users. Additional analyses were conducted by age group and sex. Results Our cohort included 1333 patients with psoriasis: 183 TNFi/UST users, 625 current CSA users and 525 previous CSA users. TNFi/UST users were at a lower risk of DAAD versus previous CSA users (hazard ratio 0.48, 95% confidence intervals: 0.28–0.94). The reduction in risk among TNFi/UST users was not statistically significant versus current CSA users. Similar results were observed across different age groups and sex. Conclusion Among patients with psoriasis receiving CSA, those who were subsequently dispensed TNFi/UST were at a lower risk of DAAD compared to those who did not receive these agents.

Abstract Bullous pemphigoid and psoriasis are two well‐characterised chronic autoimmune diseases that may be triggered by drugs, infections or vaccines. The coexistence of the two is a rare event but is more extraordinary if incited by messenger RNA (mRNA) COVID‐19 vaccination. A 62‐year‐old Filipino male experiencing a flare‐up of his long‐standing psoriasis vulgaris presented with new onset tense blisters on the legs 2 days after his first booster dose of mRNA (Pfizer‐BioNTech) vaccination. The clinical, skin punch biopsy, direct immunofluorescence and enzyme‐linked immunosorbent assay were consistent with bullous pemphigoid. Complete resolution of the vesicles and bullae with no new lesions and flattening of psoriasis plaques were observed after 1 month of treatment of systemic corticosteroids and corticosteroid‐sparing agents. An association may exist between bullous pemphigoid development and mRNA COVID‐19 vaccination.

Abstract Skin is the first barrier against external threats, and skin immune dysfunction leads to multiple diseases. Psoriasis is an inflammatory, chronic, common, immune‐related skin disease that affects more than 125 million people worldwide. RNA interference (RNAi) therapy is superior to traditional therapies, but rapid degradation and poor cell uptake are the greatest obstacles to its clinical transformation. The transdermal delivery of siRNA and controllable assembly/disassembly of nanodrug delivery systems can maximize the therapeutic effect. Tetrahedral framework nucleic acid (tFNA) is undoubtedly the best carrier for the transdermal transport of genes due to its excellent noninvasive transdermal effect and editability. The authors combine acid‐responsive tannic acid (TA), RNase H‐responsive sequences, siRNA, and tFNA into a novel transdermal RNAi drug with controllable assembly and disassembly: STT. STT has heightened resistance to enzyme, serum, and lysosomal degradation, and its size is similar to that of tFNA, enabling easy transdermal transport. After transdermal administration, STT can specifically silence nuclear factor kappa‐B (NF‐κB) p65, thereby maintaining the stability of the skin's microenvironment and reshaping normal skin immune defense. This work demonstrates the advantages of STT in RNAi therapy and the potential for future treatment of skin‐related diseases.

Background Psoriasis is a chronic inflammatory condition associated with coronary artery disease risk. Uptake of oxidized low‐density lipoprotein by the lectin‐like low‐density lipoprotein receptor‐1 triggers release of the soluble extracellular domain of the receptor (sLOX‐1). We sought to characterize the relationship between sLOX‐1, inflammation, and coronary plaque progression in psoriasis. Methods and Results A total of 327 patients with psoriasis had serum sLOX‐1 levels measured at baseline by an ELISA‐based assay. Stratification by high‐sensitivity C‐reactive protein ≥4.0 mg/L (quartile 4), identified 81 participants who had coronary plaque phenotyping at baseline and were followed longitudinally by coronary computed tomography angiography. Subjects within high‐sensitivity C‐reactive protein quartile 4 were middle‐aged (51.47±12.62 years), predominantly men (54.3%) with moderate psoriasis disease severity (6.60 [interquartile range, 3.30–13.40]). In the study cohort, participants with sLOX‐1 above the median displayed increased vulnerable coronary plaque features. At baseline, sLOX‐1 was associated with total burden (rho=0.296; P=0.01), noncalcified burden (rho=0.286; P=0.02), fibro‐fatty burden (rho=0.346; P=0.004), and necrotic burden (rho=0.394; P=0.002). A strong relationship between sLOX‐1, noncalcified burden (β=0.19; P=0.03), and fibro‐fatty burden (β=0.29; P=0.003) was found in fully adjusted models at baseline and 1‐ and 4‐year follow‐up. Finally, coronary plaque features progressed over 1 year regardless of biologic or systemic treatment in subjects with high sLOX‐1. Conclusions Patients with psoriasis with both high sLOX‐1 and high‐sensitivity C‐reactive protein levels have increased coronary plaque burden associated with atherosclerotic plaque progression independent of biologic and systemic treatment. Thus, sLOX‐1 might be considered as a promising marker in coronary artery disease risk estimation beyond traditional risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01778569.

Key Clinical Message This clinical case demonstrates quick resolution of nail psoriasis in a patient treated with risankizumab, highlighting the role of IL‐23 in the pathogenesis of nail psoriasis.

Key Clinical Message Coronavirus disease 2019 (COVID‐19) is known to trigger systemic inflammation and elicit immune responses, which may disrupt the delicate balance of cytokines involved in psoriatic regulation. Compared to other therapies in dermatology, biologics used for immune‐mediated dermatological diseases have been more extensively studied during the COVID‐19 pandemic. Herein, we report a case of flare‐up of previously well‐controlled psoriasis shortly after infection with COVID‐19, with treatment transition from secukinumab to adalimumab.