OBJECTIVE:To inform implementation of a long-standing, personalized exercise therapy programme in patients with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) and severe functional limitations, we estimated the prevalence of severe functional limitations and described current physical therapy (PT) use. METHOD:In a multicentre cross-sectional study, rheumatologists at 11 medical centres used a checklist to record severe functional limitations in consecutive outpatients with RA or axSpA. The same patients were invited to complete an online questionnaire on current or recent PT use, including duration where applicable. RESULTS:Rheumatologists completed the checklist for 612 patients. Severe functional limitations were identified in 58/443 in RA (13%; 95% confidence interval 10-16) and 27/169 in axSpA (16%; 95% confidence interval 11-21). The online questionnaire was sent to 486 patients, of whom 251 (52%) responded (191 RA; 60 axSpA). Among respondents, 39/251 (16%) were classified by rheumatologists as having severe functional limitations. Among those who were severely limited, 13/39 (33%) reported individual long-term PT; among those without severe functional limitations, 46/212 (22%) reported individual long-term PT. CONCLUSION:Our study shows a mismatch between eligibility and current PT use: long-term PT appeared underused among patients with severe functional limitations and potentially overused among those without them. Non-recommended passive modalities were frequently used. A systematic implementation strategy is needed to facilitate the uptake of the evidence-based PT in clinical practice for patients with RA or axSpA and severe functional limitations.
OBJECTIVE:A self-management app, Urika, was developed to remotely monitor and support patients when initiating urate-lowering therapy (ULT). The objective was to test the overall feasibility of a future randomized controlled trial of a digital treat-to-target gout-care approach using Urika in secondary care. METHOD:Feasibility was tested among patients with gout in specialized healthcare over 3 months. The predefined set of feasibility criteria included aspects of technical, operational, and trial feasibility, as well as the feasibility of collecting clinical outcomes. Overall feasibility would be deemed acceptable if ≥ 70% of the predefined criteria were achieved. Patient participants entered their measured serum urate, ULT medication, start dose, and flare medication into the app. The app provided instructions about dose escalations. Patient characteristics and patient-reported outcome measures were collected by digital questionnaires, and app experiences were collected in semi-structured telephone interviews. RESULTS:The study included 21 males aged 29-71 years. In total, 27/31 (87%) of the predefined feasibility criteria were achieved, 85% of patients rated their satisfaction with the app ≥ 8 on a 0-10 numeric rating scale, and 90% reported being satisfied/very satisfied with the gout treatment. Ten patients were interviewed, giving mainly positive feedback on the Urika app. No safety issues were identified in this small sample. CONCLUSION:The overall feasibility of the Urika app and the study logistics were satisfactory. The study results have been used to improve the app functions and decide study logistics in an ongoing randomized controlled trial of a digital treat-to-target gout-care approach.Trial Registration Number: ClinicalTrials.gov: NCT06211322, registered 18 January 2024.
OBJECTIVE:To define the demographics of Kawasaki disease (KD) in Sweden during a 32 year period. METHOD:Routinely collected administrative and healthcare data from nationwide Swedish registers were collected for this population-based cohort study. The case definition was individuals under the age of 25 and diagnosed with KD from 1987 to 2018. Main measures included incidence rate, year and month of diagnosis, sex and age at diagnosis, patient's and parents' world region of birth, and home county. RESULTS:In total, 1917 cases were identified. Median age at diagnosis was 2.82 years (interquartile range 1.47-5.13) and 62% were males. Relative incidence rates in winter [1.29, 95% confidence interval (CI) 1.14-1.47] and spring (1.21, 95% CI 1.07-1.38) were higher than in the reference season (summer), while incidence over the study period varied geographically across counties, with no discernible pattern. The incidence rate in the population increased during the 32 year period from 3.6 to 12.1 (95% CI 9.1-15.2) per 100 000 under-5-year-olds during the last 5 years of the study. This increase related mainly to cases with one or two parents of non-Swedish, predominantly Asian and African, origin. Two significant peaks in incidence rates in 2008 and 2015 were also observed, mainly relating to cases with two Swedish-born parents. CONCLUSION:Our study confirms the age and sex distribution as well as seasonal variation and occurrence of peak years of KD. Migration patterns were associated with increasing numbers of KD, which is important to consider for healthcare planning and for defining risk groups.
OBJECTIVES:To compare Sámi and non-Sámi patients with psoriatic arthritis (PsA) and evaluate potential differences in treatment and joint damage. METHOD:A total of 424 adult PsA patients meeting the ClASsification for Psoriatic ARthritis (CASPAR) criteria were recruited from the Norwegian Arthritis Registry and hospitals in northern Norway. A questionnaire from the SAMINOR (a study in regions with Sámi and Norwegian populations) was used to identify Sámi and non-Sámi patients. Demographic and clinical characteristics, joint damage, and disease-modifying anti-rheumatic drug treatment data were compared between the groups. Binary logistic regression was used to adjust for age and gender differences. RESULTS:Sixty Sámi and 364 non-Sámi patients were identified, and the groups were comparable in demographic characteristics and disease activity measurements. Sámi patients experienced more joint damage than non-Sámi patients (42% vs 26%, p = 0.010), and the highest rate was observed among Sámi men (p = 0.005). Sámi patients also had a higher prevalence of arthritis and axial involvement (92% vs 76%, p = 0.007 vs 32% vs 20%, p = 0.033). In addition, Sámi men showed significant underutilization of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) (83% vs 92%, p = 0.031), particularly methotrexate (68% vs 90%, p = 0.002). CONCLUSION:Sámi PsA patients show higher rates of axial involvement, arthritis, and joint damage than their non-Sámi peers. Furthermore, Sámi patients demonstrate underutilization of csDMARDs. These findings underscore the importance of implementing culturally adapted healthcare strategies to improve treatment outcomes for Sámi patients with PsA.
OBJECTIVE:Positron emission tomography/computed tomography (PET/CT) enables the visualization of vascular inflammation in Takayasu arteritis (TAK). However, the prognostic significance of PET/CT-based arterial involvement remains unclear. This study aimed to classify the distribution patterns of vascular lesions in treatment-naïve TAK using PET/CT and evaluate their association with clinical outcomes. METHOD:Patients with TAK who underwent PET/CT before treatment initiation were retrospectively analysed. Hierarchical clustering was performed based on the distribution of arterial 18F-fluorodeoxyglucose uptake. The clinical outcomes, including relapse and large-vessel complications, were analysed according to the resulting clusters using survival analyses. Longitudinal changes in PET/CT findings and clinical activity were assessed. RESULTS:Thirty patients (90% women) were included, with a median follow-up of 4.8 years and median age at diagnosis of 48 years. Three distinct PET/CT-based clusters were identified: thoracic (43%), diffuse (30%), and localized (27%). The diffuse type showed the highest relapse rate 24.1/100 person-years, p = 0.04), whereas the thoracic type tended to be associated with more vascular complications (13.9/100 person-years, p = 0.12). The Numano classification did not always correspond to PET/CT-based clusters or predict clinical outcomes. A PET Vascular Activity Score ≥ 7 was associated with relapse but not with vascular complications. PET/CT activity persisted despite clinical inactivity in some cases, which may cause future relapse. CONCLUSION:PET/CT-based classification suggested three distinct TAK subtypes with different clinical outcomes. The diffuse type was significantly associated with relapse, whereas the thoracic type caused vascular complications. PET/CT provided superior risk stratification compared to the conventional classification.
OBJECTIVE:To determine whether serum immunoglobulin A (IgA) identifies an extra-articular-prone phenotype in axial spondyloarthritis (axSpA) and assess its clinical utility. METHOD:We retrospectively analysed 402 patients with axSpA. Elevated IgA was defined as > 4.0 g/L. Associations with extra-articular manifestations (EAMs) were evaluated by logistic regression, and time to first EAM by Kaplan-Meier and Cox models. Discrimination and clinical utility were assessed. RESULTS:During follow-up, 45.5% of patients developed ≥1 EAM and 8.7% developed ≥2. Elevated IgA occurred in 15.0% overall but was more common in patients with multiple EAMs (40.6%) than in those without (10.9%) or with a single EAM (14.7%); corresponding odds ratios were 5.57 (95% CI 2.41-12.89, p < 0.001) and 3.98 (1.66-9.54). Elevated IgA predicted ≥2 EAMs with 40.6% sensitivity, 89.0% specificity, and an area under the curve of 0.65, rising to 0.78 when combined with C-reactive protein (CRP). Kaplan-Meier analysis showed reduced EAM-free survival with elevated IgA (p = 0.008). In Cox models, elevated IgA independently predicted incident EAMs (hazard ratio 2.28, 95% CI 1.18-4.40, p = 0.014). Decision-curve analysis indicated a positive net benefit. Crohn's disease was overrepresented among patients with elevated IgA (33.3% vs 11.4%, p < 0.0001). CONCLUSION:Elevated serum IgA delineates an intestinally biased, extra-articular-prone axSpA phenotype and provides actionable information beyond CRP, supporting the integration of IgA-based risk stratification into EAM surveillance.
OBJECTIVE:To describe the epidemiology, organ involvement, histopathological patterns, and clinical management of immunoglobulin G4-related disease (IgG4-RD) in Stockholm County, Sweden. METHOD:Patients with an International Classification of Diseases, 10th revision, Swedish Edition (ICD-10-SE) diagnosis of IgG4-RD recorded between 2019 and 2023 were identified from the Swedish National Patient Register, encompassing all diagnoses recorded in inpatient and specialist outpatient care. Clinical data, laboratory results, histopathology reports, and treatment information were obtained through systematic medical record review. RESULTS:In total, 112 patients with a registered IgG4-RD diagnosis were identified, of which 95 diagnoses were confirmed after medical record review. The cohort was predominantly male (68%), and 60% had disease involvement of two or more organs. Elevated serum IgG4 was present in 71% of patients. The pancreas, hepatobiliary system, and kidneys were the most frequently affected organs, while salivary gland involvement was comparatively uncommon. Among patients who underwent biopsy (76%), a majority showed histopathological features supportive of IgG4-RD, although only a minority fulfilled multiple histopathological criteria. Comorbidities at the time of diagnosis were similar to those observed in the general older population, although an elevated prevalence of nasal polyposis and asthma was observed. Most patients received systemic glucocorticoids, either alone or in combination with rituximab. Overall, the prognosis was favourable, with high remission rates. CONCLUSION:IgG4-RD in Stockholm County shows a pancreatohepatobiliary-renal dominant pattern, with relatively few glandular cases compared to Asian and US cohorts. Histopathological confirmation was supportive in most biopsied patients, although many affected organs were not biopsied.
OBJECTIVE:To describe the clinical features of six patients diagnosed with both rheumatoid arthritis (RA) and granulomatosis with polyangiitis (GPA), as well as their anti-neutrophil cytoplasmic antibody (ANCA) status and human leucocyte antigen (HLA) phenotypes. METHOD:Patients diagnosed with both RA and GPA were identified among people followed at our department for ANCA-associated vasculitis. Genomic HLA typing was performed using routine methods. RESULTS:We identified six patients diagnosed with both RA and GPA. All patients were women, five were myeloperoxidase (MPO)-ANCA positive, one was proteinase 3 (PR3)-ANCA positive, five had erosive joint disease, and all patients were immunoglobulin M-rheumatoid factor and/or anti-cyclic citrullinated peptide antibody positive. Five had localized GPA, one had systemic GPA, four had subglottic stenosis, and three had saddle nose deformity. The median time between the two diagnoses was 13 (range 7-17) years. Four patients had RA before GPA, while two had GPA before RA. The MPO-ANCA-positive patients all had an HLA-DR4/DQ8/DPB1*04:01 phenotype. CONCLUSION:In this case series of patients diagnosed with both RA and GPA, a long latency period between the two diagnoses was observed in all cases. All patients were women, the majority had erosive arthritis, and many patients were affected by saddle nose deformity and/or subglottic stenosis. MPO-ANCA was present in the majority of patients, which has not been described before. All patients were HLA-DR4/DQ8/DPB1*04:01 positive. These findings may contribute to our understanding of the underlying pathogenesis and the clinical recognition of this rare disease overlap.
OBJECTIVE:Avacopan (AVAC), an oral selective C5a receptor inhibitor, has been approved for treatment in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Outside randomized controlled studies, real-world data are scarce. The aim of this study was to provide further insight into the clinical experience of AVAC. METHOD:We analysed data from 16 patients with severe AAV included in an AVAC compassionate use programme. Disease activity was estimated with the Birmingham Vasculitis Activity Score (BVAS). Fatigue was assessed using the Multidimensional Assessment of Fatigue (MAF). RESULTS:Thirteen patients (81%) were diagnosed with granulomatosis with polyangiitis (GPA) and three (19%) with microscopic polyangiitis. The mean age at AVAC initiation was 51 (range 16-74) years. The median [interquartile range (IQR)] BVAS score was 10 (3.25-13.25) at baseline and 0 (0-0) at 6 months (p < 0.0001). All but one reached clinical remission. Prednisolone was tapered from a median (IQR) dose of 25 (20-60) to 2.5 (0-5) mg/day at 6 months (p = 0.0001). Eight patients discontinued prednisolone [median time 2.5 month1 week to 10 months)]. The median (IQR) estimated glomerular filtration rate in patients with renal AAV (n = 10) increased from 50 (13-75) to 58 (15.5-88) mL/min/1.73 m2 at 6 months (p = 0.055). One patient progressed to end-stage kidney disease, while another was able to discontinue haemodialysis. Serious adverse events were seen in five of the 16 patients (31.3%). The MAF score decreased, with a mean difference of 6.65 (p = 0.05) at 6 months. CONCLUSION:The use of AVAC in a case series with mainly GPA patients led to rapid clinical improvement, reduction of corticosteroid doses, and improvement in fatigue. The findings demonstrate beneficial effects of AVAC as add-on therapy in severe AAV.
OBJECTIVES:Cough is an underrecognized and atypical manifestation of giant cell arteritis (GCA), which may lead to diagnostic delay. Literature on cough in GCA is limited and lacks comprehensive data on clinical relevance. The aim of this study was to assess the frequency of cough at diagnosis in GCA patients and to compare clinical characteristics between those with and without cough. METHOD:Consecutive patients diagnosed with GCA between 2000 and 2020 and followed for ≥ 12 months at the University Hospitals Leuven (Belgium) were included retrospectively. RESULTS:We included 398 GCA patients, of whom 72 (18%) reported cough. Patients with cough were slightly younger (69.8 vs 72.3 years, p = 0.019), more frequently had constitutional symptoms (94% vs 73%, p < 0.001), and less often had polymyalgia rheumatica (26% vs 50%, p < 0.001) or permanent visual loss (3% vs 19%, p < 0.001). They had higher C-reactive protein (86 vs 68 mg/L, p = 0.003) and erythrocyte sedimentation rate (80 vs 67 mm/h, p = 0.036), and lower haemoglobin (11.3 vs 11.8 g/dL, p = 0.008) and albumin (36.7 vs 38.4 g/L, p = 0.013). Positron emission tomography total vascular score (10 vs 5, p = 0.009) was higher in GCA patients with cough. Although time to first relapse was shorter (10 vs 13 months, p = 0.018), relapse probability [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.82-1.61, p = 0.420] and the probability of discontinuing glucocorticoids were similar (HR 1.10, 95% CI 0.80-1.50, p = 0.563). CONCLUSION:GCA patients with cough may represent a distinct phenotype associated with systemic inflammation and large-vessel involvement. Further prospective studies with standardized cough assessment are needed to clarify the role of cough in GCA.
OBJECTIVE:To investigate the therapeutic potential of anti-interleukin-33 (anti-IL-33) in a collagen-induced arthritis (CIA) model and its biological effects on the aggressive phenotype of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). METHOD:The CIA model was established in DBA/1 mice, which were treated with anti-IL-33, methotrexate, or vehicle. Arthritis severity was monitored via clinical scoring. Joint histopathology, cartilage damage, bone erosion, and synovial cell proliferation were assessed using H&E staining, Safranin O-fast green staining, and micro-computed tomography (micro-CT), respectively. In vitro, human RA-FLSs were stimulated with tumour necrosis factor-α (TNF-α) and treated with anti-IL-33. Cell proliferation, apoptosis, cell-cycle distribution, migration, invasion, and IL-6 production were evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium (MTT) assay, immunofluorescence assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), Transwell assays, and enzyme-linked immunosorbent assay. RESULTS:Anti-IL-33 treatment significantly attenuated the clinical severity of arthritis and delayed disease progression in CIA mice. Histological and micro-CT analyses revealed that IL-33 blockade reduced synovial inflammation, pannus formation, and bone destruction, while preserving cartilage. In vitro, anti-IL-33 suppressed the proliferation, migration, and invasion of TNF-α-stimulated RA-FLSs. Furthermore, it promoted apoptosis, induced cell-cycle arrest at the G1 phase, and significantly down-regulated the secretion of the pro-inflammatory cytokine IL-6. CONCLUSION:IL-33 blockade effectively mitigates synovial inflammation and joint destruction by suppressing the proliferation, migration, and invasion of RA-FLSs while promoting their apoptosis. Targeting IL-33 may represent a promising strategy for the treatment of rheumatoid arthritis.
OBJECTIVE:In a previous network meta-analysis (NMA) of randomized controlled trials (RCTs), we analysed the effects of 27 potential conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), glucocorticoid (GC), and placebo in patients with rheumatoid arthritis (RA), using tender joint count as the primary outcome. The purpose of the present NMA was to investigate the relative effects of csDMARDs, GC, and placebo on radiographic joint destruction. METHOD:We identified 31 RCTs investigating 13 csDMARDs, GC, and placebo used in monotherapy, and used WinBUGS software to conduct an NMA, metaregressions, and subgroup analyses for possible confounders. The percentage annual radiographic progression rate (PARPR) was the primary outcome, while the standardized mean difference was used in a sensitivity analysis. RESULTS:Leflunomide, sulfasalazine, and injected gold were more favourable than placebo and neither more nor less favourable than methotrexate. Although the effect size was equivalent with methotrexate, GC was not statistically better than placebo with the PARPR method. Azathioprine was less favourable than methotrexate and the remaining drugs were either not different from placebo or insufficiently investigated for robust conclusions. CONCLUSION:Our study confirms that the present routine csDMARDs, methotrexate, leflunomide, and sulfasalazine, have inhibitory effects more favourable than placebo on joint destruction in RA.
OBJECTIVE:To compare the efficacy of corticosteroid and platelet-rich plasma (PRP) injections on pain and function in chronic, non-ruptured rotator cuff tendinopathies. METHOD:In a 9 month prospective randomized trial, 52 patients were assigned to receive either corticosteroid (n = 26) or PRP (n = 26) injections. Pain was assessed using a visual analogue scale (VAS), and function was evaluated with shortened Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH) and Shoulder Pain and Disability Index (SPADI) scores at baseline, 1 week, and 3 months. Adverse events were documented. RESULTS:The mean age was 62.3 ± 8.3 years, with 84.6% being female. Pain reduction was comparable between groups at 1 week (p = 0.49). At 3 months, corticosteroids achieved significantly greater pain relief (ΔVAS 3.35 vs 1.75; p = 0.02), confirmed by multivariate analysis (p = 0.01). Functional improvement was similar between groups; a non-significant trend favouring corticosteroids for QuickDASH was observed but not confirmed by multivariate analysis. Both treatments were well tolerated, with mild and transient adverse events: post-injection pain (PRP 73.1% vs CTC 53.8%) and local oedema (PRP 30.8% vs CTC 38.5%). CONCLUSION:Corticosteroids were more effective for pain reduction at 3 months, while PRP provided equivalent functional improvement. PRP may be an alternative for patients with corticosteroid contraindications. TRIAL REGISTRATION:Clinicaltrials.gov (NCT07094178).
