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.

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.

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.

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.

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.

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.

Risk factors associated with osteoporosis and fracture in psoriatic arthritis

Background:Although there are few studies mentioned there may be some relationship between psoriatic arthritis(PsA)and osteoporosis,clinical data in real world still need to be clarified in China.The aim of this study was to assess the areal and volumetric bone mineral density(BMD),frequency of fracture,and risk factors in patients with PsA.Methods:A total of one hundred PsA patients who visited Peking University First Hospital and one hundred age-and sex-matched healthy controls with DXA data were enrolled in the study.Patients with clinical fractures confirmed by X-ray during follow-up were also recorded.Clinical characteristics of the patients were recorded and compared between the abnormal BMD group and the normal BMD group,as well as between the fracture and non-fracture groups.Risk factors for fracture and low BMD were analyzed.Results:Mean BMD at the total hip and femoral neck was significantly lower in PsA patients than that in healthy controls(0.809±0.193vs.0.901±0.152 g/cm^(2),P=0.041;0.780±0.146vs.0.865±0.166 g/cm^(2),P=0.037,respectively).Moreover,lumbar spine BMD was negatively correlated with psoriasis duration,swollen joint count and DAS28-CRP(r=-0.503,-0.580,-0.438;P<0.05).Total hip BMD and femoral neck BMD were negatively correlated with HAQ(r=-0.521,-0.335;P<0.05).Fractures occurred in 29 patients during the follow-up period.Logistic regression analysis showed that older age(OR 1.132[95%CI:1.026-1.248),P<0.05],higher HAQ score(OR 1.493,95%CI:1.214-1.836,P<0.01),higher disease activity index for psoriatic arthritis(OR 1.033,95%CI:1.002-1.679,P<0.05)and hip joint involvement(OR 6.401,95%CI:4.012-44.180,P<0.05)were risk factors for fracture in the multivariate model.Conclusions:Increased risks of osteoporosis and fracture were found in PsA patients compared to healthy controls.Besides age,high disease activity and hip joint involvement were risk factors for decreased BMD and fracture.

Elevated serum Dickkopf-1 is a biomarker for bone erosion in patients with psoriatic arthritis

Background:Psoriatic arthritis(PsA)is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology.Dickkopf-1(Dkk-1)is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation.The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients.Methods:Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay(ELISA)in 69 patients with PsA and 60 controls,including 39 rheumatoid arthritis(RA)patients,and 21 healthy controls(HCs).Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA.The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed.Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA.Results:Dkk-1 was elevated in 68.1%(47/69)of the patients with PsA,46.2%(18/39)of RA patients,and 9.5%(2/21)of HCs.Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs.The level of serum Dkk-1 was correlated with a swollen joint count,and levels of complement components 3 and 4.Elevated Dkk-1 level(odds ratio=4.440,95%confidence interval:1.246-15.817,P=0.021)was identified as the risk factor for bone erosion in PsA.Conclusions:The serum level of Dkk-1 is abnormally elevated in PsA patients.The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.

Photodynamic therapy for arthritis: A promising therapeutic strategy

Photodynamic therapy(PDT)is a novel therapy that combines photosensitizers,light,and oxygen molecules to treat diseases such as joint lesions and microbial infections through photodynamic reactions.The photosensitizers are activated under specific wavelengths of laser radiation to generate reactive oxygen species,which alter the microenvironment of the diseased tissue,cause ischemia and target cell death,and thus effectively treat cancer.Now that there is growing evidence that nonlethal doses of PDT reduce inflammation and treat infections in multiple animal models of arthritis,PDT should be considered as a new option for the treatment of arthritis.This article presents a literature review of published original articles and review articles concerning photodynamic therapy and arthritis.We conducted a comprehensive literature search in PubMed,Web of Science and Google Scholar databases,excluding duplicated and irrelevant studies.In cases of duplicated research,we selected articles with higher impact factors for the review.In this review,we summarize the application and progress of PDT in the treatment of rheumatoid arthritis,osteoarthritis,psoriatic arthritis,and infectious arthritis,and clarify the advantages and limitations of PDT for arthritis.PDT offers therapeutic value for patients with inflammatory and infectious arthritis through promoting vascular occlusion,cell death,and antibacterial therapy.

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.

Nail Psoriasis: Treatment Options and Management Strategies in Special Patient Populations

Nail involvement is common in psoriasis and is considered a risk factor for and a predictor of the development of psoriatic arthritis.The treatment of nail psoriasis is challenging because of the unique anatomical structure of nails and the absence of standardized treatment protocols.Herein,we provide an up-to-date overview of the treatment options for nail psoriasis,including topical drugs and penetration enhancement strategies,traditional and novel oral drugs,and biologic agents.In addition,we highlight the available individualized management strategies in special patient populations such as pediatric patients,geriatric patients,women of childbearing age,and patients with concomitant onychomycosis or psoriatic arthritis.