The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 estimates health loss from migraine, tension-type headache, and medication-overuse headache. This study presents updated results on headache-attributed burden from 1990 to 2023, along with clinical and public health implications. Data on the prevalence, incidence, or remission of migraine, tension-type headache, and medication-overuse headache were extracted from published population-based studies. We used hierarchical Bayesian meta-regression modelling to estimate global, regional, and country-level prevalence of headache disorders. For the first time in GBD 2023, age-specific and sex-specific estimates of time in symptomatic state were applied by meta-analysing individual participant data from 41 653 individuals from the general populations of 18 countries from all parts of the world. Disability weights were applied to calculate years lived with disability (YLDs). Since medication-overuse headache is a sequela of a mistreated primary headache (due to medication overuse), its burden was reattributed to migraine or tension-type headache, informed by a meta-analysis of three longitudinal studies. In 2023, 2·9 billion individuals (95% uncertainty interval 2·6-3·1) were affected by headache disorders, with a global age-standardised prevalence of 34·6% (31·6-37·5) and a YLD rate of 541·9 (373·4-739·9) per 100 000 population, with 487·5 (323·0-678·8) per 100 000 population attributed to migraine. The prevalence rates of these headache disorders have remained stable over the past three decades. YLD rates due to headache disorders were more than twice as high in females (739·9 [511·2-1011·5] per 100 000) as in males (346·1 [240·4-481·8] per 100 000). Medication-overuse headache contributed 58·9% of the YLD estimates for tension-type headache in males and 56·1% in females, as well as 22·6% of the YLD estimates for migraines in males and 14·1% in females. Headache disorders, in particular migraine, continue to be a major global health challenge, emphasising the need for effective management and prevention strategies. Much headache-attributed burden could be averted or eliminated by avoiding overuse of medication (including over-the-counter medication), underscoring the importance of public education. Gates Foundation.
To study multidimensional factors affecting long-term mortality and causes of death in patients with systemic lupus erythematosus (SLE). 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. 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%). 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.
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. 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). 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. 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.
Giant cell arteritis (GCA) is a vasculitis that can lead to visual impairment. Jaw claudication (JC), a key clinical feature of GCA, is associated with an increased risk of visual complications. We hypothesized that the chewing gum test (CGT) could reveal JC that is not identified through anamnesis alone. We conducted a prospective multicentre study including patients with suspected GCA between October 2019 and December 2021. The CGT was performed twice, in a blinded manner, before the initiation of any corticosteroid therapy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the CGT were assessed. In total, 48 patients were included: 33 with confirmed GCA and 15 controls. Fifteen of the 33 patients with GCA had JC identified by conventional questioning, yielding a sensitivity, specificity, PPV, and NPV of 45%, 73%, 79%, and 38%, respectively. When at least one CGT was positive, the sensitivity, specificity, PPV, and NPV were 36%, 79%, 80%, and 34%, respectively. Three cases of JC not detected by conventional questioning were identified using the CGT; however, three CGT results were false positives. The combination of conventional questioning and at least one positive CGT significantly increased sensitivity from 45% to 55% (p < 0.0001). Although the relatively low sensitivity of the CGT limits its stand-alone clinical applicability, its association with conventional questioning may help to identify JC in patients with suspected GCA, thereby facilitating earlier diagnosis and potentially reducing visual complications. Large-scale studies are required to confirm these findings.
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). 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. 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. 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.
To describe the epidemiology, organ involvement, histopathological patterns, and clinical management of immunoglobulin G4-related disease (IgG4-RD) in Stockholm County, Sweden. 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. 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. 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.
To evaluate the diagnostic performance of dual-energy computed tomography (DECT), ultrasound (US), cone-beam computed tomography (CBCT), and multi-energy spectral photon-counting computed tomography (SPCCT) for detecting calcium pyrophosphate (CPP) and hydroxyapatite crystal deposition. We prospectively enrolled patients scheduled for finger-joint surgery due to osteoarthritis. Preoperative cross-sectional assessment included visual analogue scale pain, and in vivo index tests with DECT, US, and CBCT; the postoperative ex vivo index test was SPCCT of excised joint material. Reference tests comprised compensated polarized light microscopy of synovial fluid and histology with Alizarin Red S staining of excised joint material. Tests for crystals were scored on a binary basis. We calculated sensitivity, specificity, and likelihood ratios (LRs); a test with positive LR > 10 or negative LR < 0.1 was considered 'very good'. We included 12 participants, nine of whom had at least one positive reference test for calcium crystals. None of the index tests met our predefined cut-offs for a very good test. The best sensitivity and specificity were 0.29 [95% confidence interval (CI) 0.04-0.71] and 0.67 (0.09-0.99) for DECT, 0.89 (0.52-1.00) and 1.00 (0.16-1.00) for US, 0.33 (0.07-0.70) and 0.67 (0.09-0.99) for CBCT, and 1.00 (0.66-1.00) and 0.00 (0.00-0.98) for SPCCT. Wide CIs reflected the small sample size. Participants with CPP in the synovial fluid had more pain than those without. SPCCT and US had high sensitivity for calcium crystal detection, although no test achieved the strict definition of a very good test. ClinicalTrials.gov (NCT04585113).
Polymyalgia rheumatica (PMR) is diagnosed in both primary and secondary healthcare. However, general practitioners (GPs) do not report diagnostic codes to national health registers, limiting the representation of primary healthcare patients in register-based studies. We estimated the positive predictive value (PPV) of a register-based algorithm for identifying patients with PMR across healthcare sectors in Denmark. Potential patients were aged ≥50 years between 2003 and 2024. In primary healthcare, potential patients were identified by a first-time prescription of prednisolone/prednisone (PDN) issued by a GP and ≥375 mg PDN redeemed within 1 month. If other diagnoses, treated with PDN, were registered within 3 months of identification, patients were excluded. In secondary healthcare, potential patients were identified by a PMR diagnosis code in the Danish National Patient Registry (DNPR). Diagnoses were confirmed through chart review: in primary healthcare by GPs, and in secondary healthcare at two secondary hospitals and one tertiary hospital in Central Denmark Region (2013-2024). We estimated PPV with 95% confidence intervals (CIs) using the exact binomial method. PMR diagnoses were confirmed in 62% (95% CI 54-69) of patients in primary care, and 89% (95% CI 84-93) in secondary care. Among primary care patients redeeming 1000-2000 mg PDN within 2 months following diagnosis, PPV was 84% (95% CI 76-90). Among secondary care patients redeeming PDN within 2 months of diagnosis, PPV was 91% (95% CI 86-94). The algorithm provides a robust framework for register-based epidemiological studies of patients with PMR.
This study aimed to investigate the differences in clinical manifestations, serological profiles, pulmonary function, and high-resolution computed tomography (HRCT) findings between patients with anti-cyclic citrullinated peptide (CCP) antibody-negative and anti-CCP-positive rheumatoid arthritis-associated interstitial lung disease (RA-ILD). A retrospective cohort of 214 RA-ILD patients admitted to Peking University Third Hospital between December 2009 and May 2025 was analysed. Comprehensive clinical data, laboratory parameters, pulmonary function tests, and HRCT features were systematically compared between anti-CCP-negative and anti-CCP-positive groups. Among the 214 RA-ILD patients, 41 (19.2%) were anti-CCP negative and 173 (80.8%) were anti-CCP positive. Compared with the anti-CCP-positive group, the anti-CCP-negative group had a lower proportion of males (17.1% vs 36.4%, p < 0.05) and smokers (12.2% vs 28.3%, p < 0.05), but a higher prevalence of anti-SSB antibody positivity (10.8% vs 2.5%, p < 0.05). HRCT revealed fewer fibrotic features, including reticulation, honeycombing, and traction bronchiectasis (36.6% vs 67.1%, p < 0.05), and a lower prevalence of the usual interstitial pneumonia pattern (22.0% vs 43.4%, p < 0.05) in the anti-CCP-negative group. No significant intergroup differences were observed in age at RA onset, comorbidities, disease activity scores, velcro rales, or pulmonary function parameters. While anti-CCP-negative and anti-CCP-positive RA-ILD patients share many clinical similarities, the anti-CCP-negative subgroup is characterized by a distinct profile including lower frequencies of males and smoking, higher anti-SSB antibody positivity, and less severe fibrotic lesions on HRCT.
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. 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. 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). 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.
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. Consecutive patients diagnosed with GCA between 2000 and 2020 and followed for ≥ 12 months at the University Hospitals Leuven (Belgium) were included retrospectively. 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). 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.
In rheumatoid arthritis (RA), some patients experience joint pain that is disproportionate to the number of swollen joints, known as disproportionate articular pain (DP). This study aimed to clarify the prevalence and persistence of DP and to compare the outcomes across biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). From the ANSWER cohort in Japan, 5489 RA patients who initiated b/tsDMARDs between January 2010 and June 2024 were screened. DP was defined as having at least seven more tender joints (TJC) than swollen joints at baseline, and 432 patients met this criterion. Persistence of DP at 3 and 6 months was evaluated. Comparative analyses were conducted across mechanisms of action (MOAs): tumour necrosis factor-α inhibitors (TNFi), cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin (CTLA4-Ig), interleukin-6 inhibitors (IL-6i), and Janus kinase inhibitors (JAKi). DP was identified in 7.8% of RA patients. At 3 months, DP persisted in 40.7% (TNFi), 36.5% (CTLA4-Ig), 48.0% (IL-6i), and 54.4% (JAKi). At 6 months, corresponding rates were 43.8%, 38.7%, 49.3%, and 61.1%. Multivariate analysis showed that higher TJC and previous treatment with two or more b/tsDMARDs were associated with persistent DP, whereas higher C-reactive protein was protective. Within JAKi, baricitinib showed lower DP persistence compared with other JAKi. DP was present in approximately 8% of RA patients. Persistent DP was associated with higher TJC, greater number of previous b/tsDMARDs, and lower inflammation. No MOA was clearly superior; however, baricitinib may confer a relative benefit within the JAKi class.
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. 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. 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. 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.
To investigate the performance of colour Doppler lacrimal gland ultrasound (LGUS CD) for discriminating Sjögren's disease (SjD) from non-SjD sicca patients under routine clinical practice conditions. Forty patients with clinically suspected SjD underwent ocular function tests [Schirmer's test, ocular staining score (OSS)] and LGUS CD evaluation. Ultrasound images and videos were scored for both lacrimal glands using the Outcome Measures in Rheumatology (OMERACT) CD scoring system (range 0-3). Subsequently, a total score (range 0-6) was calculated for each patient. Sensitivity and specificity of LGUS CD and ocular function tests were calculated to predict SjD classification according to 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria. Construct validity of LGUS CD was assessed by determining Spearman's correlation coefficients between LGUS CD, Schirmer's test, and OSS. Twenty-three patients were classified with SjD and 17 as non-SjD sicca patients. LGUS CD sensitivity was 57% and specificity was 53% for prediction of classification according to 2016 ACR/EULAR classification criteria for SjD. Total LGUS CD score of both eyes and the individual LGUS CD score of the left and right eye did not differ significantly between SjD and non-SjD sicca patients. None of the ACR/EULAR classification criteria differed significantly between the groups with high and low LGUS CD scores. Poor correlations were determined between LGUS CD and ocular function tests (ρ = 0.028-0.187). LGUS CD demonstrated similar characteristics in SjD and non-SjD sicca patients, suggesting limited discriminatory value. Refined ultrasonographic scoring systems are needed to improve differentiation between these patient groups.
Pneumocystis pneumonia (PCP) is a serious fungal infection in immunocompromised patients. We investigated the prevalence of Pneumocystis jirovecii (PJ) colonization using oral wash polymerase chain reaction (PCR) in Danish rheumatoid arthritis (RA) patients with respiratory symptoms or recurrent pneumonia, and assessed its diagnostic utility for PCP. This secondary analysis of the AURORA study included 76 consenting adults (aged ≥ 18 years) with RA and respiratory symptoms or recurrent pneumonia. Oral wash samples were tested for PJ using a validated PCR assay. All patients underwent pulmonary assessment, including high-resolution computed tomography (HRCT). Medical records were audited for PCP diagnoses after 2 years. The mean age was 65.6 years, 63% were female, 24% received biological disease-modifying anti-rheumatic drug treatment, and 8% had received biological treatment of >3 years' duration. Only one patient (1%), treated with methotrexate and rituximab and presenting with recurrent pneumonia, cough, and dyspnoea, tested positive for PJ. HRCT showed pneumonia, interstitial lung disease (usual interstitial pneumonia pattern), bronchiectasis, and emphysema. PCP was confirmed by a respiratory physician based on clinical presentation. No other patients developed PCP during follow-up. Oral colonization with PJ was rare in this cohort of Danish RA patients with respiratory symptoms. The low prevalence of colonization and the absence of PCP in PJ-negative patients suggest that routine screening for oral PJ colonization is not warranted in this population.
Interferon regulatory factor 5 (IRF5) plays a central role in interferon-mediated inflammation and is implicated in autoimmune diseases, including systemic lupus erythematosus (SLE). Detecting IRF5 in plasma is challenging due to its low circulating levels, highlighting the need for a highly sensitive and quantitative assay. This study aimed to develop such an assay, validate the existence of previously identified IRF5 high and low subgroups in SLE, and support the potential of IRF5 as a biomarker in precision medicine. We established a solid-phase proximity ligation assay (SP-PLA) for IRF5 detection using a commercially available polyclonal antibody, which was benchmarked against two in-house recombinant antibodies. A linear calibration curve was generated using recombinant IRF5 protein (range 0.01-100 pg/µL), with a limit of detection between 0.01 and 0.05 pg/µL. EDTA-plasma samples from three SLE subgroups (n = 25 per group) were analysed. IRF5 was detectable in all SLE plasma samples using SP-PLA (mean 0.63 pg/µL; sd 1.92 pg/µL; maximum 13.54 pg/µL). The IRF5 high SLE subgroup showed significantly higher IRF5 plasma levels than the IRF5 low SLE subgroup (Dunn's post-hoc test, adjusted p < 0.05). The SP-PLA enabled sensitive and specific detection of low-level IRF5 in plasma and confirmed the presence of IRF5 high and low subgroups in SLE using a quantitative method. These findings support the potential of IRF5 as a biomarker, but validation in independent cohorts is required. The assay may facilitate patient stratification in future research and precision medicine approaches targeting the interferon pathway.
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. 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. 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. 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.
Although peripheral arthritis (PA) is common in early axial spondyloarthritis (axSpA), its influence on spinal/pelvic structural damage and disease activity remains unclear. We aimed to assess associations between PA, clinical and disease activity indices, and imaging features in early axSpA. Baseline data analysis of the Italian SPACE cohort, including patients with chronic back pain (duration ≥3 months and ≤2 years; age of onset <45 years), was conducted. axSpA was diagnosed by magnetic resonance imaging and X-rays of the sacroiliac joints. Clinical features, disease activity, and functional indices were collected at baseline, and at 12 and 24 months. Characteristics of axSpA in patients with concomitant PA were evaluated over time using descriptive statistics. A logistic regression model was built to assess associations between baseline features and PA. Ninety-one patients had axSpA (83.5% non-radiographic; 16.5% radiographic); 44% had PA. axSpA patients with PA less frequently had human leucocyte antigen B27 positivity (35% vs 43.1%; p = 0.02) and uveitis (5% vs 9.8%; p = 0.03) and more frequently had dactylitis (37.5% vs 0%; p < 0.01) and enthesitis (82.5% vs 56.9%; p = 0.02). Functional and disease activity indices improved overall. PA was independently associated with higher baseline C-reactive protein (p = 0.004) and dactylitis (p = 0.02) in multivariable analysis. axSpA patients with PA more often had other peripheral manifestations and increased disease activity and functional impairment, and revealed possible differences in axial involvement. These differences may be important in treatment decisions and warrant further investigation.
This study evaluated colchicine adherence in children and adolescents with familial Mediterranean fever (FMF) using the Medication Adherence Scale in FMF Patients (MASIF), and examined the influence of patient-related factors and family history. A cross-sectional study was conducted among 324 paediatric FMF patients (1-18 years old). Colchicine adherence was measured via MASIF, and demographic, clinical, genetic, and socioeconomic variables were analysed. Of 324 patients (mean age 11.8 ± 3.8 years), 88 (27.2%) showed good adherence and 236 (72.8%) poor adherence. Adherence was not significantly associated with sex, age group, age at diagnosis, disease severity, family history, colchicine intolerance/resistance, or biologic use. Erysipelas-like erythema was present in 28 patients (8.6%) at diagnosis and correlated with better adherence (p = 0.016). Of the 142 patients (43.8%) who self-reported regular colchicine use, MASIF indicated poor adherence in 101 (71.1%). School absenteeism was reported in 41 (46.6%) of the adherent group and 171 (72.5%) of the non-adherent group (p < 0.001). Colchicine non-adherence is frequent in paediatric FMF and largely unrelated to patient factors. Objective tools such as MASIF reveal higher non-adherence rates than self-reports and are essential for accurate evaluation in clinical decision making.
Respiratory disease contributes to the excess mortality seen in rheumatoid arthritis (RA), and chronic obstructive pulmonary disease (COPD) is frequently encountered. The aim of this study was to investigate the risk of severe acute exacerbation, pneumonia, and death among patients with RA and COPD compared with patients with COPD alone. The study population was patients with hospital-based, outpatient follow-up for COPD identified from the Danish COPD registry. Diagnoses of RA, information about hospitalizations for acute exacerbations of COPD (AECOPD), pneumonia, and vital status were obtained from National Health Registries. Follow-up was 12 months after first outpatient contact for COPD. Hospitalizations for AECOPD and pneumonia, and risk of death in COPD with or without RA, were compared using Cox proportional hazards regression analysis. Covariates were balanced using inverse probability of treatment (IPT) weighting. The study included 58 655 patients with hospital-based follow-up for COPD, 2033 (3.5%) of whom had RA. More than 25% of the cohort experienced hospitalization with AECOPD and/or pneumonia in the first year after first outpatient COPD hospital contact. IPT-weighted unadjusted Cox regression analysis showed similar risk of hospitalization with AECOPD among patients with RA and COPD [hazard ratio (HR) 1.004, 95% confidence interval (CI) 0.89-1.13] and death (HR 1.13, 95% CI 0.98-1.30), but increased risk of hospitalization for pneumonia (HR 1.26, 95% CI 1.11-1.42). The increased risk of pneumonia associated with RA may be attributed to immunosuppression. The findings should lead to increased focus on optimizing COPD therapies and preventive measures.