Pembrolizumab-induced psoriatic arthritis treated with disease-modifying anti-rheumatic drugs in a patient with gastric cancer:A case report

BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.

Umbilical cord blood stem cell treatment for a patient with psoriatic arthritis

Clinical and laboratory results document psoriatic arthritis in a 56-year old patient. The symptoms did not resolve with standard treatments(nonsteroidal anti-inflammatory drugs, steroids and methotrexate). TNF-alpha inhibitors(certolizumab pegol and adalimumab) were added to the treatment regime, with some adverse effects. A trial of human umbilical cord stem cell therapy was then initiated. The stem cells were enriched and concentrated from whole cord blood, by removal of erythrocytes and centrifugation. The patient received several infusions of cord blood stem cells, through intravenous and intra-articular injections. These stem cell treatments correlated with remission of symptoms(joint pain and psoriatic plaques) and normalized serologic results for the inflammatory markers C-reactive protein and erythrocyte sedimentation rate. These improvements were noted within the first thirty days post-treatment, and were sustained for more than one year. The results of this trial suggest that cord blood stem cells may have important therapeutic value for patients with psoriatic arthritis, particularly for those who cannot tolerate standard treatments.

Anti-and non-tumor necrosis factor-α-targeted therapies effects on insulin resistance in rheumatoid arthritis,psoriatic arthritis and ankylosing spondylitis

In addition toβ-cell failure with inadequate insulin secretion,the crucial mechanism leading to establishment of diabetes mellitus(DM)is the resistance of target cells to insulin,i.e.insulin resistance(IR),indicating a requirement of beyond-normal insulin concentrations to maintain euglycemic status and an ineffective strength of transduction signaling from the receptor,downstream to the substrates of insulin action.IR is a common feature of most metabolic disorders,particularly type II DM as well as some cases of type I DM.A variety of human inammatory disorders with increased levels of proinflammatory cytokines,including tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β,have been reported to be associated with an increased risk of IR.Autoimmunemediated arthritis conditions,including rheumatoid arthritis(RA),psoriatic arthritis(PsA)and ankylosing spondylitis(AS),with the involvement of proinflammatory cytokines as their central pathogenesis,have been demonstrated to be associated with IR,especially during the active disease state.There is an increasing trend towards using biologic agents and small molecule-targeted drugs to treat such disorders.In this review,we focus on the effects of anti-TNF-α-and non-TNF-α-targeted therapies on IR in patients with RA,PsA and AS.Anti-TNF-αtherapy,IL-1 blockade,IL-6 antagonist,Janus kinase inhibitor and phosphodiesterase type 4 blocker can reduce IR and improve diabetic hyper-glycemia in autoimmune-mediated arthritis.

Association between uveitis and psoriatic disease: a systematic review and Meta-analysis based on the evidence from cohort studies

AIM: To conduct a systematic review and Meta-analysis to examine the association between uveitis and psoriatic disease, and to evaluate whether one condition predisposes individuals to the other. METHODS: We performed a comprehensive search of Pub Med and EMBASE to identify cohort studies examining the association between uveitis and psoriatic disease [psoriasis and/or psoriatic arthritis(Ps A)]. We used a random-effects model to calculate the pooled relative risks(RRs) adjusted for confounders, along with the 95% confidence intervals(CIs). RESULTS: This Meta-analysis included a total of 6 studies and a maximum of 80 178 648 participants. Compared with non-psoriatic controls, uveitis risk was significantly elevated in patients with psoriasis(RR=1.49;95%CI: 1.08-2.07), and Ps A(RR=3.16;95%CI: 2.16-4.63). Furthermore, pre-existing uveitis was associated with a significantly increased risk of psoriasis(RR=1.62;95%CI: 1.44-1.83), and Ps A(RR=4.44;95%CI: 3.52-5.60).CONCLUSION: The results of this systematic review and Meta-analysis suggest an overall positive bidirectional association between uveitis and psoriatic disease(psoriasis and Ps A), warranting increased awareness among clinicians involved in the management of these two conditions.Therefore, there remains a need for more detailed studies of the possible common pathogenesis of psoriatic disease and uveitis.

Psoriatic arthritis: Epidemiology, diagnosis, and treatment

Our understanding of psoriatic arthritis has evolved as new knowledge of the disease has emerged. However, the exact prevalence of psoriatic arthritis is unknown, and its pathogenesis has not been fully elucidated. Genetic, environmental, and immunologic factors have all been implicated in disease development. Early diagnosis and treatment have become primary objectives in clinical rheumatology. Psoriatic arthritis not only causes functional impairment, but also increases mortality risk of patients. The advent of new therapeutic agents capable of arresting the progression of joint damage is expected. However, early psoriatic arthritis assessment remains limited. The objectives of this article are to outline the epidemiology, diagnosis, and treatment of psoriatic arthritis and to suggest a paradigm for identifying early psoriatic arthritis patients.

Genetic Factors and Psoriatic Arthritis

Psoriatic arthritis (PsA) is a complex immune-mediated disease and its pathogenesis depends both on genetic factors and environment. PsA patients may present a wide range of clinical manifestations including skin and nail abnormalities. Indeed, articular involvement is variable too. Disease development relies on a heterogeneous net made of multiple cytokines pathways which are regulated by several factors including human leucocyte antigen (HLA) expression, miRNAs, microbiome. Among genetic polymorphisms which can lead to abnormal cytokine expression, tumor necrosis factor (TNF) polymorphisms have been studied. Thus, leading to the development of new therapeutic agents. Finally, further studies on genetic factors and epigenetics will give new insights into this complex disorder. The aim of this mini-review is to provide the reader with a summary of the fundamental and most innovative aspects of genetic and epigenetic factors involved in the PsA, thus including human leucocyte antigen (HLA) expression, tumor necrosis factor (TNF) polymorphisms, micro RNAs and microbiome.

Targeting the Inflammation Culprit in Patients with Psoriasis/Psoriatic Arthritis and Associated Cardiovascular Comorbidities. Is the IL-17 Inhibitor the New Kid on the Block?

Despite half-century old, but comprehensive national and international guidance, evidence of clinical effectiveness and widespread agreement on management of risk factors along with sophisticated measures for primary and secondary prevention of major cardiovascular events, cardiovascular disease remains the dominant cause of death and disability world-wide. Life style changes at population-level (e.g., lower salt and saturated fat consumption or reduced/banned amount of industrially-produced trans fatty acids in specific products, etc.) or changes at individual level (e.g., targeting modifiable risk factors/life style changes affecting smoking/tobacco use, poor diet, high blood cholesterol, high blood pressure, insufficient physical activity, overweight/obesity) have reduced coronary heart disease mortality to variable extent in different countries (mostly so reported in Finland, Iceland and Sweden) at the beginning of the new century. Overall, however, cardiovascular mortality is estimated to increase in the next coming years until 2030 at a cost exceeding US $1044 billion. Several decades of status quo are also noted in the therapeutic spectrum of cardiovascular disease, mainly consisting of variations to LDL-C lowering agents, antihypertensives, anticoagulants, antiplatelets and fibrinolytics. Most of the therapeutic interventions are “tertiary” in nature (probably some 60%), meaning that treatment is instituted once the individual has developed a pathologic condition;“secondary prevention” may cover some 25%?-?30% (meant to prevent re-occurrence of the condition or occurrence of complications) while “primary prevention” is left with 10%?-?15% share (most commonly implying life style changes at individual level and rarely pharmacological intervention). For almost three decades, the so-called inflammatory hypothesis has been promoted as a reasonable pathogenetic theory behind initiation and growth of atherosclerotic plaque (Alexander RW, 1994;Ross R, 1999). With the discovery of molecular and cellular pathways that promote atherosclerosis and the role of cytokines as inflammatory messengers, the concept as such—inflammation, has received a primordial role?in atherogenesis. The present review paper aims at ascertaining the role of inflammation as a common pathogenetic denominator of cardiovascular disease in patients primarily treated for their psoriasis and/or psoriatic arthritis.

Role of leptin in the progression of psoriatic,rheumatoid and osteoarthritis

Leptin,an adipokine responsible for body weight regulation,may be involved in pathological processesrelated to inflammation in joint disorders including rheumatoid arthritis(RA),osteoarthritis,and psoriatic arthritis(PsA).These arthropathies have been associated with a wide range of systemic and inflammatory con-ditions including cardiovascular disease,obesity,and metabolic syndrome.As a potent mediator of immune responses,leptin has been found in some studies to play a role in these disorders.Furthermore,current potent biologic treatments effectively used in Ps A including ustekinumab(an interleukin 12/23 blocker) and ada-limumab(a tumor necrosis factor-alpha blocker also used in RA) have been found to increase leptin receptor expression in human macrophages.This literature review aims to further investigate the role leptin may play in the disease activity of these arthropathies.

A Needs-Based Rheumatologist Education Program on Treating to Target in Psoriatic Arthritis and Spondyloarthropathy: Insights and Challenges

Objectives: To determine if comparative practice data and education for rheumatologists would change physician behavior for monitoring and treating psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods: Participating rheumatologists each performed a chart audit on 20 patients with PsA and SpA. Accredited education (determined by a survey and chart audits) and results of chart audits (comparing to other rheumatologists) were provided for each participant (intervention). Eight months later, a repeat chart audit by each participant was conducted on another 20 PsA and SpA patients. Changes in measurements collected, treatment given and patient characteristics pre and post intervention were analyzed. Results: Nine rheumatologists received the intervention. At baseline, most routinely monitored PsA and SpA for clinical and laboratory markers. In PsA, there was no change post-intervention in performing SJC (96%), TJC (≥91%), ESR (≥70%), CRP (≥73%), and CDAI (25%). In SpA, there were increased measurements of inflammatory markers (54% pre vs. 61% post for CRP), more NSAID use and decreased physical exam measures and HAQ but no significant changes. There were no major treatment differences pre and post intervention including NSAIDs, DMARDs and biologics. Conclusions: The rheumatologists frequently performed measurements of disease activity, did not change significantly with educational intervention so there may have been little room for improvement and many patients were already in a low disease state. Calculation of composite scores did not increase in PsA. The validity of physical exam and BASDAI as a measurement of disease activity were noted as concerns in applying a treat-to-target approach in SpA. Significance and Innovation: This study did not show a significant change in behavior for rheumatologists who had education based on care gaps and needs assessment in psoriatic arthritis and spondyloarthropathy. The rheumatologists identified that disease activity is difficult to determine with usual care in SpA and thought some measures lacked validity.

What have we learned about non-involved psoriatic skin from large-scale expression studies?

Psoriasis is a chronic inflammatory skin disorder; its genetic background has been widely studied in recent decades. Recognition of novel factors contributing to the pathogenesis of this disorder was facilitated by potent molecular biology tools developed during the 1990 s. Large-scale gene expression studies, including differential display and microarray, have been used in experimental dermatology to a great extent; moreover, skin was one of the first organs analyzed using these methods. We performed our first comprehensive gene expression analysis in 2000. With the help of differential display and microarray, we have discovered several novel factors contributing to the inherited susceptibility for psoriasis, including the EDA+ fibronectin splice variant and PRINS. The long non-coding PRINS RNA is expressed at higher levels in non-involved skin compared to healthy and involved psoriatic epidermis and might be a factor contributing cellular stress responses and, specifically, to the development of psoriatic symptoms. This review summarizes the most important results of our large-scale gene expression studies.

Effects of a Nurse-Led Educational Intervention for Chinese Adult Patients with Psoriatic Arthritis: A Case-Control Study

The aim of this study was to evaluate the effect of an individual nurse-led educational intervention for patients with psoriatic arthritis (PsA). This was a case-control study. The case group consisted of six individual educational sessions delivered by a nurse. A total of 40 patients with PsA joined in this study: the case group (n = 20) and the control group (n = 18). After a 6-week intervention, the case group had significantly better management for the severity of arthritis symptoms (p < 0.05), better psychological well-being and significant lower levels of anxiety (p < 0.05), and depression score (p < 0.01), and reported better improvement of physical and psychological domain of quality of life (QOL) (both p values < 0.05) than the control group. In conclusion, this nurse-led individual education intervention has statistically significant benefits for the management of clinical symptoms of arthritis and for psychological well-being and QOL in patients with PsA.

Psoriatic arthritis: clinical patterns, rheumatoid factor, anti-cyclic citrullinated peptide and human leukocyte antigen risk alleles

Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.Both rheumatoid factor and anti-cyclic citrullinated peptide antibodies positive psoriatic arthritis patients may be in risk for development of symmetrical polyarthritis pattern.Symmetrical polyarthritis pattern was predominant(42%)among clinical pattern of psoriatic arthritis.Among 10 rheumatoid factor positive patients,8(80%)patients had symmetrical polyarthritis pattern and out of 7 anti-cyclic citrullinated peptide antibody positive patients,7(100%)patients had symmetrical polyarthritis pattern.Association of anti-cyclic citrullinated peptide(P=0.008)and rheumatoid factor(P=0.006)showed statistical significance with symmetrical polyarthritis pattern.Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 were predominantly found in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Background:Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.It is usually seronegative in nature but a small percentage of patients may be positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Anti-cyclic citrullinated peptide and rheumatoid factor are highly specific for rheumatoid arthritis but their role is not clear in psoriatic arthritis.The prevalence and prognostic value of anti-cyclic citrullinated peptide antibody and rheumatoid factor in psoriatic arthritis patients is not well known.The aim of this study was therefore to investigate the prevalence of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in psoriatic arthritis patients and assess their clinical associations and also to see the distribution of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in anti-cyclic citrullinated peptide antibody and rheumatoid factor positive psoriatic arthritis patients.Methods:Fifty patients with psoriatic arthritis were tested for the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Polymerase chain reaction was done with sequence specific primer for detection of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Data on five clinical patterns of rheumatological manifestations of psoriatic arthritis patients were collected prospectively on all patients and statistically compared between anti-cyclic citrullinated peptide,rheumatoid factor positive and negative patients by chi-square test.We also see the distribution of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in anti-cyclic citrullinated peptide antibody and rheumatoid factor positive psoriatic arthritis patients.Results:Among 50 psoriatic arthritis patients,rheumatoid arthritis test was positive in 10(20%)patients and anti-cyclic citrullinated peptide was positive in 7(14%)patients.Symmetrical polyarthritis pattern is predominant among clinical pattern of psoriatic arthritis which was found in 21(42%)patients.Among 7 anti-cyclic citrullinated peptide positive psoriatic arthritis patients,symmetrical polyarthritis pattern is predominant and it was found in 7(100%)patients.Among 10 rheumatoid factor positive psoriatic arthritis patients,symmetrical polyarthritis pattern is predominant and it was found in 8(80%)patients.In this study,symmetrical polyarthritis pattern is statistically associated with anti-cyclic citrullinated peptide positive psoriatic arthritis patients(P=0.008)and rheumatoid factor positive psoriatic arthritis patients(P=0.006).Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 were predominantly found in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Conclusion:Both rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients may be in risk for development of symmetrical polyarthritis pattern.Among rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients,Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 alleles were more frequently found alleles.

Diagnosis and treatment of psoriatic arthritis with concealed rash: a case report

Psoriatic arthritis is a kind of arthritis associated with psoriasis. The clinical manifestations of psoriatic arthritis with arthritis as the first symptom are often similar to ankylosing spondylitis and rheumatoid arthritis. Thus differential diagnosis should be made in clinical practice so as to improve the therapeutic effect. Psoriatic arthritis skin lesions are usually papules or plaques, with scales on the surface and punctate hemorrhage on the basement. About 10% of patients with psoriatic arthritis have skin rash after the onset of arthritis. In order to provide a reference for clinicians, our study the analyzed the clinical diagnosis of psoriatic arthritis in combination with a case of psoriatic arthritis with concealed skin rash and related literatures.

Prevalence of psoriatic arthritis in Chinese population with psoriasis:A multicenter study conducted by experienced rheumatologists

Background:Reports on the prevalence of psoriatic arthritis(PsA)among Chinese patients with psoriasis are very limited.This study,conducted by rheumatologists,estimated the prevalence of PsA in a large number of Chinese patients with psoriasis.Methods:Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited.All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA.All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists.Results:A total of 2434 psoriasis patients,including 1561 males and 873 females,were enrolled.Both the questionnaire and rheumatologists’examinations were completed in the dermatology clinics.The results identified 252 patients with PsA,comprising 168 males and 84 females.The overall prevalence of PsA among psoriasis patients was 10.4%(95%confidence interval[95%CI],9.1%-11.7%).By sex,the prevalence was 10.8%(95%CI,9.2%-12.5%)for males and 9.6%(95%CI,7.7%-11.9%)for females and there was no significant sex difference in the prevalence of PsA(P=0.38).Of the 252 PsA patients,125(49.6%,95%CI,41.3%-59.1%)were newly diagnosed by rheumatologists.Consequently,the prevalence of undiagnosed PsA among psoriasis patients was 5.2%(95%CI,4.4%-6.2%).Conclusion:The prevalence of PsA in the Chinese population with psoriasis is about 10.4%,which is almost double that of previous reports in the Chinese population,but lower than that in Caucasians.

Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR)

Background:The clinical features of enthesitis in patients with psoriatic arthritis(PsA)have been reported in some Western countries,but data in China are very limited.This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts.Methods:Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis(CREPAR)(December 2018 to June 2021)were included.Data including demographics,clinical characteristics,disease activity measures,and treatment were collected at enrollment.Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada(SPARCC),Maastricht ankylosing spondylitis enthesitis score(MASES),and Leeds enthesitis index(LEI)indices.A multivariable logistic model was used to identify factors related to enthesitis.We also compared our results with those of other cohorts.Results:In total,1074 PsA patients were included,308(28.7%)of whom had enthesitis.The average number of enthesitis was 3.3±2.8(range:1.0–18.0).More than half of the patients(165,53.6%)had one or two tender entheseal sites.Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis,reported a higher proportion of PsA duration over 5 years,and had a higher percentage of axial involvement and greater disease activity.Multivariable logistic regression showed that axial involvement(odds ratio[OR]2.21,95%confidence interval[CI],1.59–3.08;P<0.001),psoriasis area and severity index(PASI)(OR:1.03,95%CI:1.01–1.04;P=0.002),and disease activity score 28-C reactive protein(DAS28-CRP)(OR:1.25,95%CI:1.01–1.55;P=0.037)were associated with enthesitis.Compared with the results of other studies,Chinese patients with enthesitis had a younger age,lower body mass index(BMI),a higher rate of positive human leukocyte antigen(HLA)-B27,more frequent dactylitis,and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs’(csDMARDs)use.Conclusions:Enthesitis is a common condition among Chinese patients with PsA.It is important to evaluate entheses in both peripheral and axial sites.

Investigating the gut microbiota's influence on psoriasis and psoriatic arthritis risk: a Mendelian randomization analysis

Background:Numerous investigations have revealed the interplay between gut microbiota(GM)and psoriasis(Ps)and psoriatic arthri-tis(PsA).However,the causal relationship between them remains unknown.Methods:We curated a collection of genetic variants(P<1×10^(-5))associated with GM(n=18340)derived from the MiBioGen study.To explore the intricate relationship between GM and Ps as well as PsA,we harnessed the comprehensive resources of the FinnGen database,encompassing a vast cohort of individuals,including 4510 Ps cases and 212242 controls and 1637 PsA cases and 212242 controls.Mendelian randomization(MR)was used,including an inverse variance weighting method,followed by a sensitivity analysis to verify the robustness of the results.Results:For Ps,some bacterial taxa,including Lactococcus,Ruminiclostridium 5,and Eubacterium fissicatena,were identified as risk factors;but Odoribacter demonstrated a protective effect against Ps.In the case of PsA,Lactococcus,Verrucomicrobiales,Akkermansia,Coprococ-cus 1,and Verrucomicrobiaceae were identified as risk factors;Odoribacter and Rikenellaceae exhibited a protective effect against the developmentof PsA.Conclusion:Our study establishes a causal link between the GM and Ps and PsA.These findings provide insights into the underlying mechanisms and suggest potential therapeutic targets.

Treatment of primary nasal tuberculosis with anti-tumor necrosis factor immunotherapy:A case report

BACKGROUND Primary nasal tuberculosis(TB)is a rare form of extrapulmonary TB,particularly in patients receiving anti-tumor necrosis factor(TNF)immunotherapy.As a result,its diagnosis remains challenging.CASE SUMMARY A 58-year-old male patient presented to the ear,nose,and throat department with right-sided nasal obstruction and bloody discharge for 1 month.He was diagnosed with psoriatic arthritis and received anti-TNF immunotherapy for 3 years prior to presentation.Biopsy findings revealed chronic granulomatous inammation and a few acid-fast bacilli,suggestive of primary nasal TB.He was referred to our TB management department for treatment with oral anti-TB agents.After 9 months,the nasal lesions had disappeared.No recurrence was noted during follow-up.CONCLUSION The diagnosis of primary nasal TB should be considered in patients receiving TNF antagonists who exhibit thickening and crusting of the nasal septum mucosa or inferior turbinate,particularly when pathological findings suggest granulomatous inflammation.

A novel treatment for psoriatic arthritis:Janus kinase inhibitors

Psoriatic arthritis(PsA)is a type of chronic inflammatory arthritis which is associated with psoriasis.The early recognition and treatment for PsA are of critical importance.Janus kinase(JAK)inhibitors,as a kind of orally small molecules,have emerged as an encouraging class of drug in PsA treatment.This review provides a discussion of the role and current status of JAK inhibitors in the control of PsA.There are three JAK inhibitors approved for use in autoimmune diseases,for example,tofacitinib,baricitinib,and upadacitinib,and only tofacitinib has been approved in PsA treatment.The clinical trials of upadacitinib and filgotinib in PsA patients are undergoing.The efficacy and safety of these agents were briefly discussed.Although there are still issues in terms of their efficacy and safety currently,JAK inhibitors are expected to benefit more PsA patients in future.

Layered dissolving microneedles as a need-based delivery system to simultaneously alleviate skin and joint lesions in psoriatic arthritis

Psoriatic arthritis(PsA)is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints,and tailoring specific treatment strategies for simultaneously delivering different drugs to different action sites in PsA remains challenging.We developed a need-based layered dissolving microneedle(MN)system loading immunosuppressant tacrolimus(TAC)and antiinflammatory diclofenac(DIC)in different layers of MNs,i.e.,TD-MN,which aims to specifically deliver TAC and DIC to skin and articular cavity,achieving simultaneous alleviation of psoriatic skin and arthritic joint lesions in PsA.In vitro and in vivo skin permeation demonstrated that the inter-layer retained TAC within the skin of~100μm,while the tip-layer delivered DIC up to~300μm into the articular cavity.TD-MN not only efficiently decreased the psoriasis area and severity index scores and recovered the thickened epidermis of imiquimod-induced psoriasis but also alleviated carrageenan/kaolin-induced arthritis even better than DIC injection through reducing joint swelling,muscle atrophy,and cartilage destruction.Importantly,TD-MN significantly inhibited the serum TNF-αand IL-17 A in psoriatic and arthritic rats.The results support that this approach represents a promising alternative to multi-administration of different drugs for comorbidity,providing a convenient and effective strategy for meeting the requirements of PsA treatment.

Association of the Late Cornified Envelope-3 Genes with Psoriasis and Psoriatic Arthritis:A Systematic Review

Psoriasis （Ps） and psoriatic arthritis （PsA） are genetically complex diseases with strong genetic evidence. Recently, susceptibility genes for Ps and PsA have been identified within the late cornified envelop （LCE） gene cluster, especially the cluster 3 （LCE3） genes. It is noteworthy that the deletion of LCE3B and LCE3C （LCE3C_LCE3B-del） is significantly associated with these two diseases. Gene-gene interactions between LCE3 genes and other genes are associated with Ps and PsA. LCE3 genes also have pleiotropic effect on some autoimmune diseases, such as rheumatoid arthritis, atopic dermatitis and systemic lupus erythematosus. Further studies need to focus on the potential function of LCE3 genes in the pathogenesis of Ps and PsA in the future.