Scandinavian Journal of Rheumatology最新文献

Objective: To study multidimensional factors affecting long-term mortality and causes of death in patients with systemic lupus erythematosus (SLE).

Method: A cohort of 224 SLE patients from the Helsinki University Hospital was established in the early 2000s. Personal interviews, examinations, and chart reviews followed a protocol that included demographics, clinical data, education, socioeconomic factors, lifestyle, and laboratory tests. Causes of death were obtained from the official death certificate statistics of Statistics Finland.

Results: The mean age of the patients was 47.4 years, and the median follow-up duration was 20.5 years. Eighty-two patients (36.6%) had died. Survival rates at 5, 10, and 20 years were 94.8%, 85.3%, and 63.1%, respectively. The overall standardized mortality ratio was 2.73 (95% confidence interval 2.20-3.39). In univariate analyses, baseline factors associated with mortality included age, disease duration, body mass index (BMI), education, income, damage score, comorbidities, renal failure, and smoking history. In multivariable analyses, independent predictors of mortality were age, damage score, and renal failure, and a trend was observed for BMI and smoking history. Common primary causes of death included cardiovascular diseases (CVDs) (29 patients, 35%), malignancies (22, 27%), and SLE (10, 12%). Infections were the immediate cause of death in 16 cases (20%).

Conclusion: Multidimensional factors are associated with increased long-term mortality in SLE, and independent predictors include age, damage score, and renal failure. To improve the outcome of SLE, our results emphasize active treatment of CVDs and their risk factors, major organ manifestations of the disease and infections, and targeted cancer screening.

Objective: To assess the prevalence of organ-specific autoimmunity (OSA) among patients with primary Sjögren's disease (SjD), and its association with clinical and serological variables and disease activity.

Method: We included 328 patients with SjD according to ACR/EULAR criteria. We recorded the following types of OSA: gastrointestinal [primary biliary cholangitis (PBC), autoimmune hepatitis (AH), coeliac disease], haematological (pernicious anaemia, haemolytic anaemia, idiopathic thrombocytopenia purpura), neurological (myasthenia gravis), dermatological (vitiligo, alopecia areata), and endocrinological (autoimmune thyroid disease and type 1 diabetes). We also registered demographics, basal Schirmer I test, non-stimulated whole salivary flow, serological variables, treatment (ever), and basal and cumulative EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score at last follow-up.

Results: We found OSA in 122 patients (37.9%), the most frequent being autoimmune hypothyroidism (n = 56), PBC (n = 28), and AH (n = 8). OSA preceded SjD in 37 patients (30.3%), followed it in 62 (50.8%), and was concomitant in 23 (18.8%). In logistic regression analysis comparing patients with OSA (concomitant/post-SjD diagnosis) versus those without OSA, the variables associated with OSA were anti-Ro/SSA [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.20-0.97, p = 0.04], disease duration (OR 1.03, 95% CI 1.005-1.06, p = 0.01), and use of methotrexate (OR 0.32, 95% CI 0.55-0.73, p = 0.007) and azathioprine (OR 2.12, 95% CI 1.14-3.84, p = 0.01).

Conclusion: One-third of patients with primary SjD had OSA, with endocrine involvement being the most common. OSA may precede, follow, or accompany the diagnosis of SjD, and is not associated with higher disease activity. Monitoring for OSA is important as it contributes to comorbidity in these patients.

Objective: To assess pregnancy and delivery outcomes in women with idiopathic inflammatory myopathies (IIMs) before and after diagnosis, in relation to maternal and IIM characteristics.

Method: We identified women with IIM aged 18-40 years diagnosed at Karolinska University Hospital, and included in the Swedish nationwide myositis register (SweMyoNet) 2006-2022. Clinical data before and during pregnancy, and pregnancy and delivery outcomes were extracted from medical charts, and compared to background data of the Swedish general obstetric population during the same period.

Results: We identified 34 births among 21 women during 2006-2021, classified into two groups: births occurring up to 5 years before (pre-IIM, n = 10) and births after IIM diagnosis (post-IIM, n = 24). We observed higher frequencies for all IIM births versus the general obstetric population: caesarean delivery (29% vs 21%), labour induction (27% vs 18%), and instrumental delivery (21% vs 9.1%). These outcomes were similarly frequent in pre- and post-IIM births. Conversely, the proportion of preterm births was lower in IIM births than in the general population (3.0% vs 5.6%). Overall, IIM disease activity was low at time of pregnancy according to Manual Muscle Test-8, creatinine kinase, and glucocorticoid doses.

Conclusion: Women with IIM, both before and after diagnosis, had higher proportions of labour induction, caesarean delivery, and instrumental delivery than the general population, regardless of low IIM disease activity at time of pregnancy. The increased proportions of these outcomes also in pre-IIM births may indicate an impact of pro-inflammation and autoimmunity on reproductive health before diagnosis.

Objective: In current practice, intravenous prednisolone is administered as pretreatment to rituximab (RTX) to prevent infusion-related reactions (IRRs). This retrospective observational cohort study investigated whether 50 mg oral prednisolone is as effective as 50 mg intravenous methylprednisolone in preventing IRRs in rheumatoid arthritis (RA) patients, as this could potentially be a more practical, patient-friendly, and cost-effective alternative.

Method: Since January 2022, the local RTX pretreatment protocol changed from 50 mg methylprednisolone intravenously to 50 mg prednisolone orally. All RTX infusions in RA patients, administered between 31 January 2020 and 30 January 2024, were examined for the occurrence of IRRs. The adjusted odds ratio (OR) for IRRs was calculated for oral versus intravenous prednisolone administration. All IRRs were evaluated for symptoms, severity, type, and outcome of reaction.

Results: In total, 2253 RTX infusions in 515 patients were included, 976 with oral and 1277 with intravenous premedication. IRRs were reported after 84 infusions (3.7%). The adjusted OR was non-significantly in favour of oral treatment (OR 0.61, 95% confidence interval 0.30-1.20). IRRs were mostly mild and required little or no intervention, and a trend towards lower IRR risk for lower RTX dosing and when using concomitant disease-modifying anti-rheumatic drugs was observed.

Conclusion: Oral prednisolone pretreatment to RTX does not result in more infusion-related reactions in patients with RA, and may therefore, based on other advantages, be preferable to intravenous glucocorticoids.

Objective: The combination of bone destruction and new bone formation is characteristic of spondyloarthritis. The proinflammatory cytokine interleukin-17A (IL-17A) is known to be central to the disease pathology, but immune regulatory mechanisms are poorly understood. We investigate the programmed cell death-1 (PD-1) pathway in patients with axial spondyloarthritis (axSpA) and the relationship between PD-1 and IL-17A.

Method: We analysed blood and synovial fluid from patients with long-standing axSpA and newly diagnosed patients undergoing 1 year of adalimumab treatment. We measured soluble programmed cell death-1 (sPD-1) and sPD ligand-2 (sPD-L2) levels and investigated their correlation with disease activity markers. Surface expression of PD-1 on lymphocytes was determined, and production of IL-17A in the presence of recombinant human (rh) PD-1 was investigated. Facet joint biopsies from axSpA patients undergoing surgery were stained for the presence of PD-1 and C-C chemokine receptor-6 (CCR6).

Results: Plasma levels of sPD-1 and sPD-L2 were increased in both early and long-standing axSpA, but unaffected by 1 year of adalimumab treatment, and levels did not correlate with disease activity scores or progression. PD-1 expression was increased on synovial fluid mononuclear cells. Compared with peripheral blood mononuclear cells from healthy controls, those from axSpA patients produced more IL-17A when cultured with rhPD-1. PD-1 and CCR6 were present in facet joint biopsies.

Conclusion: We suggest a dual role for the PD-1 pathway in the pathogenesis of axSpA, acting in the inflamed microenvironment, with sPD-1 being suggestive of continued low immune activation.

Objective: To examine the demographic and clinical features of paediatric familial Mediterranean fever (FMF) patients with a heterozygous Mediterranean fever (MEFV) gene mutation, focusing on colchicine discontinuation and factors linked to sustained remission.

Method: This retrospective study included 2325 paediatric FMF patients followed at a tertiary rheumatology clinic between August 2016 and February 2024. Of these, 1246 carried a heterozygous MEFV mutation, and 87 had stopped colchicine. Discontinuation was either physician decision (PD) or initiated by family/patient decision (FD). Demographic data, clinical symptoms, colchicine use, and MEFV variants were recorded. Patients were monitored after discontinuation to assess remission and the need for retreatment.

Results: Of 87 patients, 47 (54%) were discontinued under PD and 40 (46%) under FD. The median discontinuation age was 10.8 years in PD and 11.7 years in FD. Colchicine was reinitiated in 25 patients (28.7%): 11 (4.0%) from PD and 14 (56.0%) from FD. Drug-free remission was maintained in 62 patients (71.3%), including 36 PD (58.1%) and 26 FD (41.9%) (p = 0.45). The pre-discontinuation asymptomatic period was significantly longer in PD (p < 0.01). PD patients also had a lower risk of reinitiating treatment than FD patients (p = 0.046). Older age at discontinuation was associated with sustained remission (p = 0.01).

Conclusion: Colchicine withdrawal under physician supervision and at older ages is associated with a lower risk of relapse and greater likelihood of maintaining drug-free remission.

Objectives: Calprotectin (S100A8/A9) is an established inflammatory marker in rheumatoid arthritis (RA), but its role in psoriatic arthritis (PsA) is less studied. This study evaluated plasma calprotectin as a biomarker of inflammatory activity in PsA by assessing its association with ultrasound-detected synovitis before and during treatment with a biological disease-modifying anti-rheumatic drug (bDMARD). The potential of S100A12, vascular endothelial growth factor, interleukin-6 (IL-6), IL-17A, IL-23, and C-X-C motif chemokine ligand 10 (CXCL10) was also explored.

Method: Forty-three PsA patients initiating bDMARD therapy were assessed clinically and by ultrasound at baseline and after 3, 6, 9, and 12 months. Biomarkers were measured using enzyme-linked immunosorbent assays and Luminex assays. Changes were analysed using the Wilcoxon signed-rank test, and correlations with Spearman's rank analysis.

Results: Mean (± SD) age was 47.6 (± 12.9) years, 60.5% were women, and median disease duration was 10 years (interquartile range 4.2-21.9). Significant reductions were observed in joint counts and in the Disease Activity Index for Psoriatic Arthritis, Disease Activity Score for 28 joints including CRP, and Bath Ankylosing Spondylitis Disease Activity Index. Baseline levels of calprotectin, S100A12, IL-6, IL-17A, IL-23, and CXCL10 were higher in PsA than in controls (p < 0.05). Calprotectin, S100A12, and IL-6 levels decreased during follow-up (p < 0.05). No clinically relevant correlations between the ultrasound scores and inflammatory markers were observed.

Conclusion: Calprotectin levels were elevated in PsA patients and decreased with treatment but showed no clinically significant correlation with ultrasound-detected synovitis. Further studies are needed, particularly in cohorts with higher levels of inflammation.

Objective: The aim of the study was to analyse associations between anti-inflammatory treatment before a first acute myocardial infarction (AMI) and survival up to 365 days post-AMI in patients with and without rheumatoid arthritis (RA).

Method: Data for 199 071 patients with a first AMI during 2006-2017, including 3725 RA patients, and for anti-inflammatory medical treatment during the 6 months before a first AMI, were drawn from Swedish registries. Drugs were categorized as corticosteroids, non-steroidal anti-inflammatory drugs, conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs), tumour necrosis factor inhibitors (anti-TNFs), or other biological DMARDs. Multivariable logistic regression analysis was used to assess mortality associations up to 30 days and multivariable Cox proportional hazard models to assess associations from 31 to 365 days.

Results: No treatment was associated with survival within 30 days after the AMI. From 31 to 365 days post-AMI, corticosteroid treatment was associated with increased mortality [in RA: hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.27-1.62; without RA: HR 1.37, 95% CI 1.33-1.41]. csDMARDs were associated with increased survival in RA patients (HR 0.86, 95% CI 0.78-0.96), as were anti-TNF treatments (HR 0.72, 95% CI 0.56-0.94). Among non-RA patients, csDMARDs were associated with increased mortality (HR 1.14, 95% CI 1.04-1.24).

Conclusion: Anti-inflammatory treatment was not associated with mortality within 30 days after a first AMI. From 31 to 365 days post-AMI, corticosteroid treatment was associated with increased mortality risk for all patients, and csDMARDs and anti-TNFs were associated with increased survival for RA patients.