Arthritis Flare Research Articles

Arthritis after SARS-CoV-2 infection.

In COVID-19, the pivotal cytokines that provoke severe disease in the lung are similar to those usually targeted by drugs used for treating rheumatoid arthritis. Although COVID-19 is not yet considered as a trigger for rheumatoid arthritis, this similarity has led to the suspicion that COVID-19 might be a risk factor for inducing a rheumatoid arthritis flare.1 Recently, arthralgia and arthritis have been reported after SARS-CoV-2 infection in three patients that were negative for rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA).

Comment on: Association between environmental air pollution and rheumatoid arthritis flares.

Comment on: Association between environmental air pollution and rheumatoid arthritis flares.

Association between environmental air pollution and rheumatoid arthritis flares.

Environmental air pollution has been linked to the pathogenesis of RA. Nevertheless, evidence linking higher concentrations of air pollutants with the risk of RA reactivations is missing. The objective of the present study was to determine the association between RA flares and air pollution. We collected longitudinal data of patients affected by RA and of the daily concentration of air pollutants in the Verona area. We designed a case-crossover study. We compared the exposure to pollutants in the 30-day and 60-day periods preceding an arthritic flare referent to the 30-day and 60-day preceding a low-disease activity visit. The study included 888 patients with RA with 3396 follow-up visits; 13636 daily air pollution records were retrieved. We found an exposure-response relationship between the concentration of air pollutants and the risk of having abnormal CRP levels. Patients exposed to greater concentrations of air pollutants were at higher risk of having CRP levels ≥5 mg/l. Concentrations of CO, NO, NO2, NOx, PM10, PM2.5 and O3 were higher in the 60-day period preceding a flare. We found a striking association between air pollution and RA disease severity and reactivations in a cohort of patients followed over a 5-year period. The exposure to high levels of air pollutants was associated with increased CRP levels and a higher risk of experiencing a flare of arthritis. This excessive risk was evident at very low levels of exposure.

Is gene expression among women with rheumatoid arthritis dysregulated during a postpartum flare?

BackgroundTo evaluate our hypotheses that, when rheumatoid arthritis (RA) flares postpartum, gene expression patterns are altered compared to (a) healthy women, (b) RA women whose disease activity is low or in remission postpartum, and (c) pre-pregnancy expression profiles.MethodsTwelve women with RA and five healthy women were included in this pilot study. RA disease activity and postpartum flare were assessed using the Clinical Disease Activity Index (CDAI). Total RNA from frozen whole blood was used for RNA sequencing. Differential gene expression within the same women (within-group) over time, i.e., postpartum vs. third trimester (T3) or pre-pregnancy (T0), were examined, using a significance threshold of q < 0.05 and fold-change ≥ 2.ResultsNine of the women with RA experienced a flare postpartum (RAFlare), while three had low disease activity or were in remission (RANoFlare) during that time frame. Numerous immune-related genes were differentially expressed postpartum (vs. T3) during a flare. Fold-changes in expression from T3 to postpartum were mostly comparable between the RAFlare and healthy groups. At 3 months postpartum, compared to healthy women, several genes were significantly differentially expressed only among the RAFlare women, and not among the RANoFlare women. Some of these genes were among those whose “normal” expression was significantly modulated postpartum, and the postpartum expression patterns were significantly altered during the RA flare. There were also some genes that were significantly differentially expressed in RAFlare compared to both healthy and RANoFlare women, even though their expression was not significantly modulated postpartum. Furthermore, while postpartum expression profiles were similar to those at pre-pregnancy among healthy women, significant differences were found between those time points among the RAFlare women.ConclusionsThe large majority of gene expression changes between T3 and 3 months postpartum among RA women who flared postpartum reflected normal postpartum changes also seen among healthy women. Nonetheless, during a postpartum flare, a set of immune-related genes showed dysregulated expression compared to healthy women and women with RA whose disease activity was low or in remission during the same time frame, while other genes demonstrated significant differences in expression compared to RA pre-pregnancy levels.

Sleep Disturbances are a Significant Predictor of Chikungunya Arthritis Flare Severity.

Objective:The primary objective of this research was to explore the link between sleep and flare pain associated with chikungunya virus (CHIKV) infection. The secondary objective was to investigate if cytokines and T regulatory (Treg) cells have an influence on this relationship.Methods:A cross-sectional study was performed using data collected in Barranquilla, Colombia, which enrolled patients with and without chronic arthritis with a history of chikungunya infection. Flare severity was measured by a version of the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) flare questionnaire adapted for CHIKV arthritis, including metrics for pain, difficulty with physical activity, fatigue, stiffness and difficulty maintaining social activities due to arthritis that contribute to flare severity. In addition, four sleep disturbance items, five inflammatory cytokine levels, four anti-inflammatory cytokine levels, and six Treg levels were measured. Then, multivariable linear regression models were used to test the direct and indirect effects of flare-pain on sleep disturbance, and to determine whether this relationship was mediated by cytokines or Tregs. Finally, the SAS CALIS procedure was used to test path models showing possible causal effects with mediators and confounds.Results:The analysis showed that sleep disturbance is positively correlated with CHIKV arthritis flare pain, and that it is a significant predictor of flare severity after adjusting for demographic variables, cytokine, and T cell levels. Further, neither T cells nor cytokines mediate the pain/sleep relationship in CHIKV arthritis.Conclusion:There is a strong association between sleep disturbance and arthritis flare pain and severity; however, this relationship is not mediated by cytokines or T cells. Since this study is unable to determine causation, further research is needed to determine the mechanism underlying the relationship between sleep disturbances and CHIKV arthritis flares.

Potential Association between Kaposi Sarcoma and Gout: An Exploratory Observational Study.

Background Kaposi sarcoma is a rare vascular mesenchymal neoplasm, associated with Human Herpes Virus 8 (HHV8). Gout is a condition clinically characterized by recurrent flares of arthritis and hyperuricemia. Following our clinical impression that patients with classical Kaposi sarcoma (CKS) have a high rate of gout, we explored this in a retrospective manner. Methods All consecutive patients diagnosed with sarcoma or carcinosarcoma within a single tertiary center between 1/2012–12/2017 were identified through the pathology department database. A cohort of CKS patients was compared with the non-Kaposi sarcoma and carcinosarcoma cohort. Data were extracted from patients' electronic medical records. Patients younger than 18 and patients without clinical data available were excluded. Association between diagnosis of gout and CKS was assessed and adjusted for risk factors. Results Three hundred and sixty-one patients were eligible for this analysis, 61 were diagnosed with CKS and 300 with other types of sarcoma. We found a higher incidence of gout in CKS patients, 11/61 (18%) patients, compared with 8/300 (2.6%) with other types of sarcoma, odds ratio (OR) 8.0 (P < 0.00001). This association persisted when adjusted for age >39 years (OR = 6.7, P < 0.00001), age and male sex (OR = 4.97, P < 0.0001), and when adjusting for multiple confounding factors and medical comorbidities. Conclusions We have demonstrated a statistically significant association between gout and CKS. As risk factors for gout were accounted for, this association may be explained by HHV8 immune-related effects. This should be further explored in vitro and in population-based studies.

Analysis of arthritis flares after achievement of inactive disease with methotrexate monotherapy in juvenile idiopathic arthritis

To investigate the frequency of arthritis flare and factors affecting occurrence of flare in children with juvenile idiopathic arthritis (JIA) who achieved inactive disease (ID) with methotrexate (MTX) monotherapy. A total of 217 patients were included. The modality of treatment discontinuation, time of MTX withdrawal, and disease course were examined retrospectively. For each patient, the first episode of ID after MTX start was evaluated. Patient follow-up was censored at occurrence of flare or at last visit with persistent ID. 170 patients (78.3%) had arthritis flare after a median of 1.6 years, whereas 47 (21.7%) maintained ID until last visit, after a median of 3 years. 54.2% of patients had discontinued MTX after ID, whereas 45.8% were still receiving MTX at the time of study censoring. Among patients who had MTX withdrawn, the median interval between ID and MTX stop was 1.5 years. Occurrence of flare was more common in patients who were still receiving MTX at study censoring than in those who had discontinued MTX (p<0.001). Most patients (78.8%) had MTX tapered over time by increasing the interval between doses. Tapering modality was comparable between patients with flare and persistent ID. Only 7.7% of the patients had a biologic DMARD started at the time of flare. Our results confirm that children with JIA who achieve ID with MTX monotherapy have a high risk of arthritis flare. The risk of flare was independent of withdrawal strategy. Most flare episodes were not treated with biologic therapy.

Efficacy and safety of a single switch from etanercept originator to etanercept biosimilar in a cohort of inflammatory arthritis

AntiTNF-α biosimilars are broadly available for the treatment of inflammatory arthritis. There are a lot of data concerning the maintenance of clinical efficacy after switching from originators to biosimilars; therefore, such a transition is increasingly encouraged both in the US and Europe. However, there are reports about flares and adverse events (AE) as a non-medical switch remains controversial due to ethical and clinical implications (efficacy, safety, tolerability). The aim of our work was to evaluate the disease activity trend after switching from etanercept originator (oETA-Enbrel) to its biosimilar (bETA-SP4/Benepali) in a cohort of patients in Turin, Piedmont, Italy. In this area, the switch to biosimilars is stalwartly encouraged. We switched 87 patients who were in a clinical state of stability from oETA to bETA: 48 patients were affected by Rheumatoid Arthritis (RA),26 by Psoriatic Arthritis (PsA) and 13 by Ankylosing Spondylitis (AS).We evaluated VAS-pain, Global-Health, CRP, number of swollen and tender joints, Disease Activity Score on 28 joints (DAS28) for RA, Disease Activity in Psoriatic Arthritis (DAPSA) for PsA, Health Assessment Questionnaire (HAQ) and Health Assessment Questionnaire for the spondyloarthropathies (HAQ-S),Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. 11/85 patients (12.6%) stopped treatment after switching to biosimilar etanercept. No difference was found between oETA and bETA in terms of efficacy. However, some arthritis flare and AE were reported. Our data regarding maintenance of efficacy and percentage of discontinuation were in line with the existing literature.

Research in Brief

Circulating CD45−CD31−PDPN+ pre-inflammatory mesenchymal (PRIME) cells, which share features with inflammatory synovial fibroblasts, increase 1–2 weeks before rheumatoid arthritis flares, according to a longitudinal RNA sequencing study by Dana Orange and colleagues. Home-collected fingerstick blood samples were assessed from one patient at 364 time points over the course of 4 years, as well as from 235 time points in three additional patients, to identify transcripts that were differentially expressed before and during flares. Consistent changes in transcriptional profiles were observed 1–2 weeks before rheumatoid arthritis flares indicating B cell activation followed by expansion of circulating PRIME cells. Levels of circulating PRIME cells decreased during flares, suggesting migration into the synovium. PRIME cells were also found to occur more frequently in blood samples of 19 additional patients with rheumatoid arthritis compared with those of healthy controls.

Vaccinations Do Not Increase Arthritis Flares in Juvenile Idiopathic Arthritis: A Study of the Relationship between Routine Childhood Vaccinations on the Australian Immunisation Schedule and Arthritis Activity in Children with Juvenile Idiopathic Arthritis.

Background Juvenile idiopathic arthritis (JIA) is a collective term for a group of inflammatory conditions of uncertain origin, which causes chronic arthritis in one or more joints. The clinical course of JIA is characterised by episodes of increased activity, termed flares. Vaccinations have previously been proposed as a “trigger” for some flares, although evidence supporting this is scant. Objective To explore whether routine childhood vaccinations are associated with an increased risk of flares of arthritis activity in children with JIA. Methods Patients aged below 6 years with a diagnosis of JIA were recruited from the Rheumatology Clinical Database at the Royal Children's Hospital, Melbourne, Australia, from 1 January 2010 to 30 April 2016. Patient immunisation status was cross-checked with the Australian Childhood Immunisation Register (ACIR). The self-controlled case series methodology (Rowhani-Rahbar et al., 2012) was applied to determine whether the risk of arthritis flares in the three months following immunisation was greater than the baseline risk for each patient. Results 138 patients were included in the study. 32 arthritis flares occurred in the 90 days following immunisation. The risk of arthritis flares during the 90 days following immunisation was reduced compared with patients' baseline risk (RR 0.59 (95% CI 0.39-0.89, p = 0.012)). Conclusion Routine childhood immunisations were not associated with arthritis flare onset in patients with JIA. The risk of arthritis flares in the 90 days following vaccination was lower than the baseline risk. In the context of COVID19, vaccination will not increase interaction with the healthcare system beyond the immunisation encounter.

RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares

BackgroundRheumatoid arthritis, like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). The molecular events leading to flares are unknown.MethodsWe established a clinical and technical protocol for repeated home collection of blood in patients with rheumatoid arthritis to allow for longitudinal RNA sequencing (RNA-seq). Specimens were obtained from 364 time points during eight flares over a period of 4 years in our index patient, as well as from 235 time points during flares in three additional patients. We identified transcripts that were differentially expressed before flares and compared these with data from synovial single-cell RNA-seq. Flow cytometry and sorted-blood-cell RNA-seq in additional patients were used to validate the findings.ResultsConsistent changes were observed in blood transcriptional profiles 1 to 2 weeks before a rheumatoid arthritis flare. B-cell activation was followed by expansion of circulating CD45−CD31−PDPN+ preinflammatory mesenchymal, or PRIME, cells in the blood from patients with rheumatoid arthritis; these cells shared features of inflammatory synovial fibroblasts. Levels of circulating PRIME cells decreased during flares in all 4 patients, and flow cytometry and sorted-cell RNA-seq confirmed the presence of PRIME cells in 19 additional patients with rheumatoid arthritis.ConclusionsLongitudinal genomic analysis of rheumatoid arthritis flares revealed PRIME cells in the blood during the period before a flare and suggested a model in which these cells become activated by B cells in the weeks before a flare and subsequently migrate out of the blood into the synovium. (Funded by the National Institutes of Health and others.)

Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial

Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5-15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4-6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov, NCT02573012. Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35-0·73) with tapered prednisone and -0·08 (-0·27 to 0·12) with continued prednisone (difference 0·61 [0·35-0·88]; p<0·0001), favouring continuing prednisone 5 mg per day for 24 weeks. Treatment was regarded as successful (defined as low disease activity at week 24, plus absence of rheumatoid arthritis flare for 24 weeks and no confirmed adrenal insufficiency) in 99 (77%) patients in the continued-prednisone group versus 85 (65%) patients in the tapered-prednisone group (relative risk 0·83; 95% CI 0·71-0·97). Serious adverse events occurred in seven (5%) patients in the tapered-prednisone group and four (3%) patients in the continued-prednisone group; no patients had symptomatic adrenal insufficiency. In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. F Hoffmann-La Roche.

Rheumatoid Arthritis Flares After Total Hip and Total Knee Arthroplasty: Outcomes at One Year.

Most patients with rheumatoid arthritis (RA) undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) have active RA and report postoperative flares; whether RA disease activity or flares increase the risk of worse pain and function scores 1 year later is unknown. Patients with RA were enrolled before THA/TKA. Patient-reported outcomes, including the Hip disability and Osteoarthritis Outcome Score (HOOS)/Knee Injury and Osteoarthritis Outcome Score (KOOS) and physician assessments of disease characteristics and activity (Disease Activity Score in 28 joints [DAS28] and Clinical Disease Activity Index), were collected before surgery. Patient-reported outcomes were repeated at 1 year. Postoperative flares were identified using the RA Flare Questionnaire weekly for 6 weeks and were defined by concordance between patient report plus physician assessment. We compared baseline characteristics and HOOS/KOOS scores using 2-sample t-test/Wilcoxon's rank sum test as well as chi-square/Fisher's exact tests. We used multivariate linear and logistic regression to determine the association of baseline characteristics, disease activity, and flares with 1-year outcomes. One-year HOOS/KOOS scores were available for 122 patients (56 with THA and 66 with TKA). Although HOOS/KOOS pain was worse for patients who experienced a flare within 6 weeks of surgery, absolute improvement was not different. In multivariable models, baseline DAS28 predicted 1-year HOOS/KOOS pain and function; each 1-unit increase in DAS28 worsened 1-year pain by 2.41 (SE 1.05; P = 0.02) and 1-year function by 4.96 (SE 1.17; P = 0.0001). Postoperative flares were not independent risk factors for pain or function scores. Higher disease activity increased the risk of worse pain and function 1 year after arthroplasty, but postoperative flares did not.

Antibodies to synthetic citrullinated peptide epitope correlate with disease activity and flares in rheumatoid arthritis.

Rheumatoid arthritis (RA), caused by the abnormal recognition of human joint cells by autoimmune antibodies, remains the world’s most prevalent autoimmune disease, with over five million people affected and as much as 4% of the population at risk of RA. To prevent rapid disease development, hormonal and anti-inflammatory therapies require fast and reliable RA diagnosis. However, difficulty in detecting early specific biomarkers for RA means that it is unclear when treatment needs to begin. Here, we combined synthesis of citrullinated peptide epitopes with molecular diagnostics to verify a new specific biomarker for early RA diagnosis and flare prediction. A fibrinogen-derived 21-amino-acid-long citrullinated peptide showed high reactivity toward autoantibodies in RA samples. Additionally, the level of antibodies to this epitope was elevated prior to flares. In contrast, other citrullinated protein variants had lower reactivity and poorer sensitivity to disease activity. In conclusion, fibrinogen-derived epitope E2 subjected to citrullination facilitated a reliable RA diagnosis with a strong correlation to disease activity. This is of a high value for the diagnosis and management of RA patients who respond poorly to treatment.

Differential DNA Methylation of Networked Signaling, Transcriptional, Innate and Adaptive Immunity, and Osteoclastogenesis Genes and Pathways in Gout.

In gout, autoinflammatory responses to urate crystals promote acute arthritis flares, but the pathogeneses of tophi, chronic synovitis, and erosion are less well understood. Defining the pathways of epigenomic immunity training can reveal novel pathogenetic factors and biomarkers. The present study was undertaken to seminally probe differential DNA methylation patterns utilizing epigenome-wide analyses in patients with gout. Peripheral blood mononuclear cells (PBMCs) were obtained from a San Diego cohort of patients with gout (n = 16) and individually matched healthy controls (n = 14). PBMC methylome data were processed with ChAMP package in R. ENCODE data and Taiji data analysis software were used to analyze transcription factor (TF)-gene networks. As an independent validation cohort, whole blood DNA samples from New Zealand Māori subjects (n = 13 patients with gout, n = 16 control subjects without gout) were analyzed. Differentially methylated loci clearly separated gout patients from controls, as determined by hierarchical clustering and principal components analyses. IL23R, which mediates granuloma formation and cell invasion, was identified as one of the multiple differentially methylated gout risk genes. Epigenome-wide analyses revealed differential methylome pathway enrichment for B and T cell receptor signaling, Th17 cell differentiation and interleukin-17 signaling, convergent longevity regulation, circadian entrainment, and AMP-activated protein kinase signaling, which are pathways that impact inflammation via insulin-like growth factor 1 receptor, phosphatidylinositol 3-kinase/Akt, NF-κB, mechanistic target of rapamycin signaling, and autophagy. The gout cohorts overlapped for 37 (52.9%) of the 70 TFs with hypomethylated sequence enrichment and for 30 (78.9%) of the 38 enriched KEGG pathways identified via TFs. Evidence of shared differentially methylated gout TF-gene networks, including the NF-κB activation-limiting TFs MEF2C and NFATC2, pointed to osteoclast differentiation as the most strongly weighted differentially methylated pathway that overlapped in both gout cohorts. These findings of differential DNA methylation of networked signaling, transcriptional, innate and adaptive immunity, and osteoclastogenesis genes and pathways suggest that they could serve as novel therapeutic targets in the management of flares, tophi, chronic synovitis, and bone erosion in patients with gout.

Serial magnetic resonance imaging and ultrasound examinations demonstrate differential inflammatory lesion patterns in soft tissue and bone upon patient-reported flares in rheumatoid arthritis

BackgroundMagnetic resonance imaging (MRI) and ultrasonography (US) are more sensitive than clinical evaluation in assessing inflammation in rheumatoid arthritis (RA). Data is scarce regarding potential link between patient-reported flares and inflammation on imaging. The aim of the study was to explore the pattern and longitudinal associations of inflammatory lesions detected by serial MRI and US in relation to patient-reported flares in patients with RA.MethodsEighty RA patients with baseline DAS28CRP < 3.2 and no swollen joints were examined at baseline and followed for 1 year. Patients were requested to contact the hospital in case of patient-reported hand flare accompanied by ≥ 1 tender and swollen joint. The 29 patients who reported hand flare had four extra visits within 4 months from flare onset comprising clinical examination, patient-reported outcomes, MRI, and US of wrists and hands. MRI synovitis/tenosynovitis/bone marrow edema (BME) and US synovitis/tenosynovitis were scored. MRI and US scores at and after the flare were compared to baseline before the flare, and associations were explored by linear mixed models for repeated measurements.ResultsSynovitis and tenosynovitis by MRI/US increased significantly at flare onset. Synovitis waned quickly, as did US tenosynovitis. BME showed delayed increase yet persisted, once the patient-reported flare had resolved, as did MRI tenosynovitis. In univariate models, patient-reported flares were associated with all MRI and US inflammatory markers, except for BME, which was only associated with SJC28 and long-lasting flares > 14 days. Independent associations were observed between patient-reported flares and tenosynovitis by MRI and US (p < 0.05).ConclusionsPatient-reported flares were linked to inflammation detected by serial MRI and US. Differential patterns of inflammatory lesion evolution were observed by serial imaging with early synovial and tenosynovial inflammation, followed by delayed-onset BME.

Risk of Toxicity After Initiating Immune Checkpoint Inhibitor Treatment in Patients With Rheumatoid Arthritis.

Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced cancer. Rheumatoid arthritis (RA) is associated with an increased risk of malignancies; however, patients with RA have been excluded from ICI trials. In this study, we evaluated risk of toxicity after initiation of ICI treatment in RA patients. We conducted a single-institution, medical records review analysis to assess the incidence of immune-related adverse events (irAEs) and autoimmune disease (AID) flares among patients with AIDs treated with ICIs from 2011 to 2018. A subgroup analysis for RA patients was performed with frequencies of irAEs and AID flares reported. Twenty-two patients with RA who were treated with ICI for malignancy were identified. At the time of ICI initiation, 86% had inactive RA disease activity. Immune-related adverse events occurred in 7 (32%) of patients, with 2 (9%) developing grade 3 (i.e., severe) irAEs. Immune checkpoint inhibitors were temporarily discontinued because of irAEs in 5 patients (23%), and permanently in 1 patient. Rheumatoid arthritis flares occurred in 12 patients (55%). Of those, 10 (83%) received oral corticosteroids with an adequate treatment response. Our analysis suggests that irAEs following ICI treatment are not increased among RA patients compared with other cancer patients. Heightened RA disease activity during ICI treatment is common, but most adverse events are manageable with oral corticosteroids, and few require permanent ICI discontinuation. A close collaboration between the oncologist and rheumatologist is advisable when considering ICIs in patients with RA.

Strukturert pasientforløp ved urinsyregikt

Pharmacological treatment and follow-up of gout is often inadequate.The patients risk repeated, painful arthritis flares and some develop chronic tophaceous gout and joint damage. Since 1 March 2017, a structured care pathway has been established for patients with gout at the Department of Rheumatology, Haukeland University Hospital. Patients were placed on preventive medication, the majority on allopurinol, and were regularly monitored. Patient education is key to the care pathway. The treatment goal is to lower the concentration of serum urate to a level below a defined threshold value (360 µmol/l for non-tophaceous gout or 300 µmol/l for tophaceous gout). Patient data were collected on a continuous basis and recorded in a research database. The care pathway is assessed after 18months. A total of 103patients have been included, of whom 93 (90%) are men, with an average age of 63 years and large variations in duration of the disease (min.-max. 0-36 years). Eight patients left the care pathway during the project. The average level of serum urate at inclusion was 446 µmol/l (min.-max. 144-751 µmol/l). The average maximum dose of allopurinol was 333mg (min.-max. 100-700mg). Survival analysis showed that three months after the start of urate-lowering therapy, 49% of the patients had achieved their analytical treatment goal. Altogether 83% achieved the goal within six months. The majority (70%) were free of flares after achieving the treatment goal. A standardised care pathway for gout enables adaptation of preventive treatment through regular monitoring. The care pathway helps the vast majority of patients to achieve treatment goals, which is crucial to avoid arthritis flares.

Genetic association of polymorphism rs2230054 in CXCR2 gene with gout in Chinese Han male population.

Neutrophils are crucial in the process of gout flare and remission. The signal transduction pathway of chemokine plays a vital role in the chemotaxis and activation of neutrophils. CXCR2 gene knocked out can avoid the acute neutrophilic inflammation stimulated by monosodium urate (MSU) crystals in mice. To investigate the relationship among CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 polymorphisms with gout arthritis flare in the Chinese Han male population, a case-control study was carried out in 412 gout patients and 508 gout-free individuals. TaqMan probes fluorescence real-time polymerase chain reaction (PCR) was used to genotype CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 SNPs. There was a clear link between CXCR2 rs2230054 T included genotypic and T allelic frequencies and gout cases (c2 = 9.286, p = 0.002 by genotype, c2 = 8.639, p = 0.003 by allele), while no significant differences were observed between the gouty arthritis group and the control group in CXCR1 rs2234671 and CXCR2 rs1126579 genotypic and allelic frequencies. Multivariate logistic regression analysis showed that the T genotype included in rs2230054 can decrease the risk of gouty arthritis (adjusted OR = 0.47; 95% CI: 0.31-0.74) compared with the CC genotype. Our study might suggest that rs2230054 in CXCR2 is associated with susceptibility to gout in Chinese males.

AKT answer relating to rheumatoid arthritis flare up

AKT answer relating to rheumatoid arthritis flare up