Seminars In Arthritis And Rheumatism[JOURNAL]
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200 papers
Immune dysregulation and infection susceptibility in Anti-MDA5 dermatomyositis.
Moore KE, Khoo T, Limaye V … +1 more , Ali SB
Semin Arthritis Rheum · 2026 Jun · PMID 41812320 · Publisher ↗
Antibodies targeting melanoma differentiation-associated gene 5 protein (MDA5) are associated with a distinct subtype of dermatomyositis characterised by cutaneous ulceration, systemic inflammation, and a high risk of ra...
Antibodies targeting melanoma differentiation-associated gene 5 protein (MDA5) are associated with a distinct subtype of dermatomyositis characterised by cutaneous ulceration, systemic inflammation, and a high risk of rapidly progressive lung disease. Beyond these manifestations, patients experience disproportionately high rates of infection compared with other inflammatory myopathies, including viral, bacterial, and fungal complications. This review synthesises cohort data demonstrating an excess burden of infections, particularly Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus, attributed to both disease-specific factors and immunosuppression. We summarise adult and paediatric cohorts in which anti-MDA5 dermatomyositis confers a higher risk of serious and opportunistic infection, early clustering of events after diagnosis, and markedly increased short-term mortality. Emerging translational evidence suggests that persistent type I and III interferon signalling, abnormal neutrophil extracellular trap formation, lymphocyte and natural killer cell depletion, and antibody-mediated vascular injury may converge to impair host defence at cutaneous and pulmonary barriers, and may also contribute to complications such as spontaneous pneumomediastinum. Current recommendations for screening, vaccination, and antimicrobial prophylaxis are largely extrapolated from other autoimmune diseases and may underestimate risk in patients with anti-MDA5 dermatomyositis. On the basis of available data, we argue that disease-specific protocols, including routine PJP prophylaxis in high-risk phenotypes and surveillance for viral reactivation, are warranted, and we outline key priorities for prospective and mechanistic studies aimed at reducing infection-related morbidity and mortality in this high-risk subgroup.
Dermatoscopy limitation and the critical role of capillaroscopy in the evaluation of systemic sclerosis and Raynaud's phenomenon among African American Veterans.
Maldonado G, Cutolo M, Frech T … +3 more , Radic M, Snow M, Smith V
Semin Arthritis Rheum · 2026 Jun · PMID 41812319 · Publisher ↗
INTRODUCTION: Nailfold capillaroscopy (NFC) is a crucial tool for assessing diagnostic microvascular abnormalities in patients with Raynaud's phenomenon (RP). While dermatoscopy is a widely accepted, cost-effective scree...
INTRODUCTION: Nailfold capillaroscopy (NFC) is a crucial tool for assessing diagnostic microvascular abnormalities in patients with Raynaud's phenomenon (RP). While dermatoscopy is a widely accepted, cost-effective screening method for systemic sclerosis (SSc), its utility depends on optimal visibility for accurate interpretation. The objective of this study was to determine if skin pigmentation affects the interpretability of nailfold evaluation. METHODS: In an Institutional Review Board-approved study at the TVHS Hospital, patients undergoing evaluation for CTD-related RP were enrolled. Images were captured using two devices: a 200X dermatoscope (smartphone focus) and a 250X Smart G-Scope (USB automatic focus). Two capillaroscopy experts independently classified each image for clarity and the overall pattern (scleroderma or non-scleroderma). Skin pigmentation was assessed using the Fitzpatrick classification (I-VI). RESULTS: A total of 38 United States (US) Veterans with RP were assessed; 28% (n = 11) were self-identified as African American. Dermatoscopy analysis yielded blurry images in 63.6% (7/11) of patients with Fitzpatrick skin tones IV, V and VI, compared to 37% (10/31) in skin tones I, II, and III. The USB-capillaroscope improved interpretability across the entire cohort, especially in skin tones IV, V and VI. Notably, a Scleroderma (SD)-pattern was detected by the USB-capillaroscope in 4 of the 5 studies that had been uninterpretable with the dermatoscope. CONCLUSIONS: In conclusion, dermatoscopy resulted in a high rate of uninterpretable examinations in patients with RP, particularly among African American Veterans. The USB-capillaroscope device significantly improved interpretability, underscoring that relying solely on dermatoscopy as a screening tool may lead to underdiagnosis of SSc.
Association between frailty and incident cancer in newly diagnosed patients with rheumatoid arthritis.
Bansal B, Gold LS, Wysham KD … +6 more , Andrews J, Heagerty P, Barton JL, Garcia JM, Makris UE, Singh N
Semin Arthritis Rheum · 2026 Jun · PMID 41812318 · Full text
BACKGROUND: Rheumatoid Arthritis (RA) is associated with an increased risk of cancer, but the underlying risk factors remain poorly understood. Frailty is linked to an increased cancer risk in the general population and...
BACKGROUND: Rheumatoid Arthritis (RA) is associated with an increased risk of cancer, but the underlying risk factors remain poorly understood. Frailty is linked to an increased cancer risk in the general population and is more common among those with RA than those without it. We aimed to evaluate frailty as a risk factor for incident cancer in RA. METHODS: We used the Merative MarketScan databases from 2008 to 2022 to identify individuals with newly diagnosed RA using diagnosis codes and pharmacy records. Patients were categorized as frail or non-frail based on a claims-based frailty index. Incident cancer was identified using a validated algorithm in administrative claims data. Unadjusted and adjusted (for demographics, Charlson comorbidity index, and healthcare utilization) Cox proportional hazards models were created to obtain hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: Among 73,240 individuals with newly diagnosed RA, 4.1% were classified as frail. Incident cancer occurred more frequently and earlier among frail individuals (1.5% vs. 1.3%; median time to diagnosis: 312 vs. 561 days). Although frailty was associated with higher unadjusted cancer incidence (HR 1.5, 95% CI: 1.3-1.8), this association was attenuated after adjustment (HR 1.1, 95% CI: 0.9-1.4). CONCLUSIONS AND RELEVANCE: Frail patients with newly diagnosed RA had a higher unadjusted incidence of cancer, and shorter time to cancer diagnosis compared to non-frail patients. However, after adjusting for demographics, comorbidities and healthcare utilization, frailty alone was not an independent predictor of increased cancer risk in this relatively younger population with RA.
Clinical characteristics and risk factors associated with objective flares in patients with dermatomyositis.
Saygin D, Wang XY, Fitzgerald KC … +7 more , Albayda J, Paik JJ, Tiniakou E, Adler B, Mammen AL, Christopher-Stine L, Mecoli CA
Semin Arthritis Rheum · 2026 Apr · PMID 41785525 · Full text
BACKGROUND: Flares in dermatomyositis (DM) are associated with increased disability, health care utilization, and reduced quality of life. We aim to determine the characteristics and risk factors of flares in patients wi...
BACKGROUND: Flares in dermatomyositis (DM) are associated with increased disability, health care utilization, and reduced quality of life. We aim to determine the characteristics and risk factors of flares in patients with DM. METHODS: Patients were included if seen at The Johns Hopkins Myositis Center and fulfilled the 2017 EULAR/ACR Classification Criteria for DM. Two authors reviewed all notes and recorded patient symptoms, exams, labs, imaging findings, and medication changes. Objective flare was defined as active disease on exam or ancillary testing that resulted in an increase in immunosuppressive therapy. Characteristics of patients and flares were summarized using descriptive statistics. We assessed the association between patient characteristics and time to first flare using Cox proportional hazards models. RESULTS: In this study with 637 patients with DM, rash was the most common finding of flare (75.7%), followed by muscle weakness (58.4%), new/worsening findings on lung function tests and/or imaging (19.0%) and arthritis (12.4%). Over 85% of the patients who reported rash, weakness, dyspnea, joint swelling, dysphagia or fever met the definition of objective flare. Black race and shorter time to diagnosis were associated with increased flare risk. Among patients with DM who experienced an objective flare, only 2-5% had a cancer diagnosis within 6-24-months of flare. In a subset of newly diagnosed patients, 26% had ≥1 flare during follow-up. The incidence rate of flares was 5.1 per 100 person-years. The average time between diagnosis and the first flare was 2.9 years (SD 2.3) ranging between 6.2 months and 10.8 years. CONCLUSION: In this tertiary care center cohort of DM patients, patient-reported symptoms of increased disease activity were often indicative of objective flare. We identified Black race and shorter time to diagnosis as risk factors for flare. Understanding these factors can inform clinicians about monitoring strategies and improved patient outcomes.
Nomenclature and abbreviation heterogeneity in immune-mediated necrotizing myopathy: A call for standardization.
Almackenzie M, Bhowmick N, Bhangoo G … +9 more , Aggarwal A, Chandra T, Patel RP, Silva RL, Mittal S, Edpuganti N, Haldule S, Keret S, Aggarwal R
Semin Arthritis Rheum · 2026 Apr · PMID 41780350 · Publisher ↗
BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is a distinct subtype of idiopathic inflammatory myopathies (IIMs). Despite its increasing recognition, considerable variability persists in its nomenclature, posin...
BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is a distinct subtype of idiopathic inflammatory myopathies (IIMs). Despite its increasing recognition, considerable variability persists in its nomenclature, posing challenges for research comparability, clinical trial design, and patient care. METHODS: We conducted a scoping review of English-language publications from November 1974 to December 2023 to assess the diversity and trends in IMNM nomenclature and abbreviations. Articles were screened for IMNM terminology and abbreviations, and categorized by publication year, region, and study design. Descriptive statistics with temporal/geographic trend analyses were performed using SPSS. RESULTS: Of 1236 articles identified, 626 met inclusion criteria, spanning 42 countries. Marked heterogeneity in terminology was observed. Regarding spelling, "necrotizing" (with "z") predominated (497 mentions) compared to "necrotising" (66 mentions), particularly after 2010 when usage of the "z" form rose sharply (463 vs. 60, respectively). For disease suffix, "myopathy" overwhelmingly replaced "myositis" in recent years (487 vs. 44 post-2010). Prefix terminology also evolved: "immune-mediated" became the dominant prefix (366 mentions post-2010) compared to "autoimmune" (91 mentions). Longitudinal analysis demonstrated that prior to 2010, terminology was inconsistent, but from 2010 onwards, coinciding with the ENMC classification, publications increasingly converged toward the standardized form immune-mediated necrotizing myopathy (IMNM). Antibody-based naming remained uncommon (7 %), and statin-associated descriptors were reported in 11 %. Abbreviations emerged in 2011, with IMNM now dominant (80 %) compared to NAM (13 %) and NM (6 %). CONCLUSION: This review highlights a clear evolution and gradual consensus in IMNM nomenclature. Despite progress toward standardization, residual variability persists, underscoring the need for unified terminology to advance research, collaboration, and clinical care.
Nailfold video capillaroscopy as a non-invasive biomarker in juvenile dermatomyositis: A longitudinal analysis of microvascular changes and clinical relevance over one year.
Ulu K, İşgüder R, Çağlayan Ş … +4 more , Türkmen Ş, Bora B, Ünsal ŞE, Sözeri B
Semin Arthritis Rheum · 2026 Apr · PMID 41764972 · Publisher ↗
OBJECTIVE: Juvenile dermatomyositis (JDM) is a rare, immune-mediated vasculopathy characterized by muscle inflammation and cutaneous involvement. This study aimed to evaluate longitudinal changes in nailfold video capill...
OBJECTIVE: Juvenile dermatomyositis (JDM) is a rare, immune-mediated vasculopathy characterized by muscle inflammation and cutaneous involvement. This study aimed to evaluate longitudinal changes in nailfold video capillaroscopy (NVC) findings and their associations with clinical disease activity and serologic markers in JDM patients over one year. METHODS: A prospective, observational study was conducted at two tertiary pediatric rheumatology clinics. Twenty children diagnosed with JDM were enrolled and followed for one year with clinical evaluations and NVC assessments performed at four-month intervals. Demographic and clinical data, Skin Disease Activity Score (Skin DAS), Childhood Myositis Assessment Scale (CMAS), patient and physician visual analog scales (VAS), and laboratory parameters (muscle enzymes, inflammatory markers) were recorded at each visit. RESULTS: Significant NVC abnormalities were observed in JDM patients compared to controls, including reduced capillary density and increased prevalence of dilated, giant, bushy, bizarre, and hemorrhagic capillaries (all p < 0.001). Capillary density showed a moderate inverse correlation with Skin DAS (r = -0.429), physician, and patient VAS. Bushy capillaries were positively associated with both patient and physician VAS. Among myositis-specific antibody subgroups, patients with anti-TIF1-γ displayed the lowest capillary density and greatest apical loop diameter. Longitudinal analyses confirmed that capillary density and apical loop diameter were significant predictors of skin disease activity over time (p < 0.05), while associations with muscle strength were less robust. CONCLUSION: Nailfold video capillaroscopy provides valuable insights into microvascular alterations in JDM and correlates with clinical disease activity, particularly cutaneous involvement. Capillaroscopic parameters, especially capillary density and apical loop diameter, hold potential as non-invasive biomarkers for monitoring disease progression and therapeutic response in juvenile dermatomyositis.
Development of clinical manifestations in individuals positive for antiphospholipid antibodies according to the 2023 ACR/EULAR serological domains.
Cantera Estefanía R, Gálvez Sánchez R, García Ruiz R … +16 more , Herrero López M, Gorostidi Álvarez I, Cruz Barquín H, Flores García JA, Oviedo Madrid M, Abando Casuso M, García Ascacíbar A, Gabrie Rodríguez LG, Hernández Hernández JL, Yáñez San Segundo L, López Hoyos M, Domínguez-García JJ, González Ponte ML, González-Mesones Galán B, Méndez Navarro GA, Martínez Taboada VM
Semin Arthritis Rheum · 2026 Apr · PMID 41763087 · Publisher ↗
INTRODUCTION: Antiphospholipid syndrome (APS) is a thrombophilic disorder defined by persistent antiphospholipid antibodies (aPL) and clinical thrombotic/obstetric events. The new 2023 ACR/EULAR classification predictive...
INTRODUCTION: Antiphospholipid syndrome (APS) is a thrombophilic disorder defined by persistent antiphospholipid antibodies (aPL) and clinical thrombotic/obstetric events. The new 2023 ACR/EULAR classification predictive validity in individuals positive for aPL remains untested. MATERIALS AND METHODS: We conducted a retrospective observational study including patients with positive LA, aCL or anti‑β2GPI between January 2018 and March 2024, all confirmed ≥12 weeks apart (except for isolated LA). Patients fulfilling 2006 Sydney criteria and/or with clinical domains 1-4 present at serological confirmation were excluded. We calculated incidence and time to clinical manifestations (domains 1-4), assessed associations with serological domains, and evaluated predictive performance of the 2023 ACR/EULAR laboratory score using logistic regression adjusting for potential confounders and ROC curve analyses. RESULTS: 985 patients were analyzed with a median follow-up of 2.84 years. Cumulative incidence of clinical events was low (<3%). Median time to onset was shortest for obstetric morbidity (0.68 years) and arterial thrombosis (ATE) (0.80 years) and longer for microvascular events (2.29 years). Moderate/high IgM aCL/anti‑β2GPI was associated with ATE in low-risk patients (OR 2.89; 95% CI 1.15-7.30; p=0.025). High‑titer IgG aCL/anti‑β2GPI was independently linked to future APS classification (OR 4.73; 95% CI 1.11-15.52; p=0.01) and reduced event-free survival (HR 3.27; 95% CI 1.17-9.16; p=0.024). The laboratory score did not predict venous thromboembolism, ATE, microvascular thrombosis, or obstetric morbidity (overall AUC 0.535). CONCLUSION: The 2023 ACR/EULAR laboratory scoring system lacked prognostic value in individuals positive for aPL. Certain serological subdomains (IgM in low‑risk arterial patients; high‑titer IgG) were modestly predictive, but the composite score failed to discriminate risk.
Towards the development of a definition of independence for individuals diagnosed with rheumatoid arthritis in remission: an 'OMERACT remission in rheumatoid arthritis patient perspective' special interest group report.
Gazel U, Barnes E, Jones B … +11 more , Terrett A, Voshaar M, Hoogland W, March L, Beaton D, Khoo T, Chin A, Shea B, Tugwell P, Proudman S, Flurey CA
Semin Arthritis Rheum · 2026 Apr · PMID 41730817 · Publisher ↗
AIMS: To discuss and refine the preliminary definition of "independence" from the patient's perspective in RA remission. METHODS: Data from a scoping review and international focus groups were presented at the OMERACT Re...
AIMS: To discuss and refine the preliminary definition of "independence" from the patient's perspective in RA remission. METHODS: Data from a scoping review and international focus groups were presented at the OMERACT Remission in RA Patient Perspective Special Interest Group (SIG) meeting in February 2024. The SIG included 40 delegates from diverse geographic regions who discussed the findings and potential refinements of the preliminary definition of independence from the patient's perspective in the context of RA remission. RESULTS: Drawing together findings from the scoping review and focus groups, the following preliminary definition of "independence" was presented for discussion: "Being able to do what you want, when you want, in the way you want to do it." Delegates emphasized the importance of capturing all aspects of independence, adjustments to the proposed preliminary definition were suggested, and some delegates requested more specificity before taking the preliminary definition forward for use in the next research stage. Issues were raised on whether cultural variation on concepts of independence was adequately captured in the qualitative work so far. For example, some cultures may value receiving support from others as a reaffirmation of social belonging and interdependence, rather than a contradiction of independence. This will need addressing in our future work to ensure cross-cultural differences in definitions of independence are not missed. The majority of delegates voted in favour of continuing the work toward defining targeted sub-domains, which will allow the group to develop an instrument to assess independence in RA remission from the patient's perspective. CONCLUSION: Consensus was reached in favour of continuing the work towards defining targeted sub-domains, which will allow the group to develop an instrument to assess independence in RA remission from the patient's perspective. However, suggestions were made to refine and improve the current definition. The next steps include refining the definition, followed by identifying and/or developing instruments to create an outcome measure for independence in RA remission.
Corrigendum to "Rheumatologist and patient perspectives on axial spondyloarthritis management and treatment satisfaction in Europe" [Seminars in Arthritis and Rheumatism 76 (Feb 2026) 152884].
Baraliakos X, Navarro-Compán V, Nikiphorou E … +9 more , Pham T, Ciccia F, Truman I, Kranz B, Castellano G, Jus A, Durán MR, Lowe J, Ramiro S
Semin Arthritis Rheum · 2026 Apr · PMID 41724607 · Publisher ↗
Abstract loading — click title to view on PubMed.
Development and validation of a multi-institutional electronic juvenile idiopathic arthritis phenotype.
Taxter A, Oberle E, Rakestraw AL … +8 more , Gangireddy S, Xu J, Ong HH, Tarvin SE, Rogerson C, Bartlett CW, Wei WQ, Patrick AE
Semin Arthritis Rheum · 2026 Apr · PMID 41722162 · Full text
BACKGROUND: Ascertaining a true cohort of juvenile idiopathic arthritis (JIA) patients using claims and electronic health record (EHR) data is challenging due to clinical complexities. This study aims to develop a comput...
BACKGROUND: Ascertaining a true cohort of juvenile idiopathic arthritis (JIA) patients using claims and electronic health record (EHR) data is challenging due to clinical complexities. This study aims to develop a computable JIA phenotype using large databases with multi-site validation and replication. METHODS: This multi-institutional study used reporting resources at three sites identified through the Maternal and Pediatric Precision in Therapeutics Hub. Subjects with ICD-9 and ICD-10-CM codes for JIA and/or psoriatic juvenile arthropathy and age ≤20 at first eligible encounter were included with exclusion of subjects with multiple ICD codes for systemic lupus erythematosus, dermatomyositis, and polymyositis. Each site manually reviewed a subset of charts to validate diagnosis. Summary statistics on variations of encounter counts with a JIA diagnosis are reported. RESULTS: There were 8093 subjects identified with potential JIA. Manual review of 253 (3 %) subjects provided a positive predictive value (PPV) of 0.74 in an initial cohort of one code count with exclusion criteria. As the number of JIA code counts required for inclusion increased, the number of subjects with JIA identified decreased, and the PPV increased. When using ≥4 code counts for JIA, age ≤20 years old, and excluding other conditions, the PPV was 0.95, with an estimated 5377 subjects. CONCLUSION: We developed and reproduced a computable and portable phenotype algorithm to identify JIA patients in structured, retrospective data, validated this across multiple institutions, and demonstrated its consistent performance across sites. This approach supports broader adoption in collaborative research networks to enhance the accuracy of JIA studies.
Pulmonary manifestations of granulomatosis with polyangiitis and microscopic polyangiitis.
Junek M, Choi S, Garner S … +15 more , Rawn S, Cox G, Khalidi N, Cuthbertson D, Koening CL, Langford CA, McAlear CA, Monach PA, Moreland LW, Pagnoux C, Seo P, Specks U, Warrington KJ, Merkel PA, Vasculitis Clinical Research Consortium
Semin Arthritis Rheum · 2026 Apr · PMID 41722161 · Full text
INTRODUCTION: ANCA-associated vasculitis (AAV) can have several pulmonary manifestations. There is limited knowledge of the epidemiology and complications of pulmonary manifestations in AAV, despite their association wit...
INTRODUCTION: ANCA-associated vasculitis (AAV) can have several pulmonary manifestations. There is limited knowledge of the epidemiology and complications of pulmonary manifestations in AAV, despite their association with increased mortality and reduced health-related quality of life. METHODS: This study retrospectively analyzed a large, multicentre longitudinal cohort of individuals with AAV followed between 2006 and 2023. Data included diagnosis, demographics, comorbidities, time of disease onset, and pulmonary manifestations of disease. Measures of both disease activity and damage were recorded. Results were summarized across disease sub-types and manifestations. RESULTS: Data from 1026 individuals were analyzed, including 860 with granulomatosis with polyangiitis (GPA) and 166 with microscopic polyangiitis (MPA). Pulmonary manifestations were seen at any time in the disease course within 81.3% of individuals: 711 (82.7%) with GPA and 123 (74.1%) with MPA. Pulmonary manifestations were reported in 644 (62.7%) at disease onset and 456 (44.4%) individuals during follow-up. Nodules and cavities, diffuse alveolar hemorrhage, and inflammatory infiltrates were the three most common manifestations across the cohort. Nodules and cavities were the most frequent manifestation seen in GPA and diffuse alveolar hemorrhage in MPA. Multiple pulmonary manifestations were seen within 51.9% of individuals with pulmonary manifestations. Pulmonary manifestations were seen in 41.4% of episodes of relapse. 17.4% of those with pulmonary manifestations sustained pulmonary damage from their disease. CONCLUSION: Pulmonary manifestations are common in AAV and are associated with permanent damage. Systematic assessments of individuals with AAV for pulmonary involvement will likely improve detection of these manifestations.
Evolution of Janus Kinase inhibitors (JAKi) prescriptions since 2015 in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study): effect of regulatory warnings.
Mongin D, Aymon R, Choquette D … +20 more , Coupal L, Codreanu C, Iannone F, Provan S, Kvien TK, Fritsch-Stork R, Nordström D, Pavelka K, Závada J, Pombo-Suarez M, Otero-Varela L, Sousa E, Rotar Z, Sidiropoulos P, Bertsias A, Courvoisier DS, Finckh A, Lauper K, Elkayam O, Furer V
Semin Arthritis Rheum · 2026 Apr · PMID 41722160 · Publisher ↗
BACKGROUND: Janus kinase inhibitors (JAKi) are effective for treating rheumatoid arthritis (RA), but post-marketing safety concerns have triggered regulatory warnings and updated guidelines. The impact of these communica...
BACKGROUND: Janus kinase inhibitors (JAKi) are effective for treating rheumatoid arthritis (RA), but post-marketing safety concerns have triggered regulatory warnings and updated guidelines. The impact of these communications on real-world prescribing remains unclear. OBJECTIVES: To assess the impact of major regulatory safety warnings on the initiation, discontinuation, and switching patterns of JAKi in RA patients, using data from 12 national registries. METHODS: This observational study analyzed 55,365 treatment courses (12559 JAKi and 42806 other bDMARDs) from 40,019 adult RA patients between 2015 and 2024. Segmented regression models examined trends around eight major regulatory events. Logistic generalized estimating equations (GEE), adjusted for demographic, disease, and treatment variables, were used. Sensitivity and subgroup analyses, including at-risk populations (age ≥65 with cardiovascular risk factors), were conducted. RESULTS: JAKi use rose from <1 % in 2015 to >20 % by 2024, with slowdowns after the 2019 FDA and 2022 EMA warnings. Initiation trends significantly slowed after the first FDA warning and the publication of increased risks for MACE and cancer in early 2021, primarily affecting tofacitinib. Discontinuations surged following the EMA's 2022 warning, again mainly affecting tofacitinib. Upadacitinib initiations also declined, and discontinuations increased after the publication of the ORAL Surveillance trial. Baricitinib use appeared to be less impacted by the safety signals, while filgotinib use steadily increased. Among the at-risk population, the rate of JAKi discontinuation significantly rose after the 2019 EMA warning. CONCLUSIONS: Regulatory safety communications significantly influenced real-world JAKi prescribing patterns. Tofacitinib was most affected through both declines in initiation and increases in discontinuation.
Is there a seasonal pattern in giant cell arteritis? Revisiting the evidence in a large monocentric cohort over 30 years.
Bond M, Bosch P, Kuenzer T … +3 more , Juche A, Bastian H, Schmidt WA
Semin Arthritis Rheum · 2026 Apr · PMID 41719606 · Publisher ↗
BACKGROUND: Despite perceived clinical clustering, the evidence for GCA seasonality is conflicting and reliance on diagnosis or biopsy dates rather than symptom onset may have masked genuine temporal patterns. OBJECTIVES...
BACKGROUND: Despite perceived clinical clustering, the evidence for GCA seasonality is conflicting and reliance on diagnosis or biopsy dates rather than symptom onset may have masked genuine temporal patterns. OBJECTIVES: To determine whether GCA exhibits a seasonal pattern of symptom onset, and to contextualise any month/season effects against long-term trends and clinical subgroups. METHODS: We analysed a monocentric cohort from Berlin-Buch (Germany, 1994-2023). Consecutive patients with clinically confirmed GCA and a documented symptom-onset date were included (n = 1149). We tested uniformity across meteorological seasons and months via exact multinomial tests and fitted negative-binomial models with b-splines for long-term trends, month-length offsets, and alternative seasonal specifications (month-by-month reference, season factor, cosinor with one/two cycles). Subgroups were defined by sex and GCA phenotype (cranial, large-vessel, mixed). Ultrasound was the primary diagnostic modality for confirming GCA. RESULTS: Seasonal distribution was balanced across seasons (winter 27.0%; spring 25.4%; summer 24.0%; autumn 23.6%; p = 0.36). Monthly distribution departed from uniformity (p = 0.002), with significantly higher incidence in January vs February (+88%), December vs February (+80%), and January vs September (+67%) with similar incidence rates across the rest of the year. Subgroup analyses revealed no consistent seasonality by sex or phenotype. CONCLUSION: Across nearly three decades, we found no convincing evidence for broad meteorological seasonality in GCA symptom onset, although short-term monthly variation, including a relative increase in December-January, was observed.
Identifying the strongest novel gene-respiratory disease interactions for rheumatoid arthritis risk.
Kronzer VL, Brooks RT, Shurtz AK … +8 more , Wang X, Atkinson EJ, Davis JM, Sparks JA, Cerhan JR, Joerns EK, Vassallo R, Crowson CS
Semin Arthritis Rheum · 2026 Apr · PMID 41713227 · Publisher ↗
OBJECTIVE: We aimed to identify the strongest individual gene-respiratory interactions for rheumatoid arthritis (RA) risk. METHODS: This case-control study used the Mayo Clinic (MC) and Mass General Brigham (MGB) biobank...
OBJECTIVE: We aimed to identify the strongest individual gene-respiratory interactions for rheumatoid arthritis (RA) risk. METHODS: This case-control study used the Mayo Clinic (MC) and Mass General Brigham (MGB) biobanks for discovery and validation, respectively. We matched criteria-confirmed incident RA cases to four non-RA controls on age, sex, and duration electronic health record (EHR) history. Genetic exposures included known RA risk alleles. We identified respiratory diseases by codes and defined "respiratory burden" as the total number of respiratory codes divided by EHR duration before index date of RA. Using logistic regression models adjusting for potential confounders, we estimated odds ratios (OR) with 95% confidence intervals (CI) for the interactions between genetic and respiratory exposures for RA risk. RESULTS: We identified 1,125 incident RA cases and 4,495 non-RA controls (mean age 64 years, 70% female in MC; 54 years, 76% female in MGB). In MC, both interstitial lung disease (OR 1.55, 95% CI 1.00-2.40) and overall respiratory burden (OR 1.67, 95% CI 1.30-2.15) were associated with incident RA. Four novel gene-respiratory interactions validated in MGB including CD83/RNF182 (rs12530098)-acute pharyngitis for seronegative RA (OR 4.06 [95% CI 1.61-10.3] MC; 3.68 [95% CI 1.42-9.56] MGB) and JARID2 (rs113532504)-asthma for seropositive RA (OR 2.66 [95% CI 1.30-5.44] MC; 1.93 [95% CI 1.20-3.08] MGB). The CD83/RNF182-acute pharyngitis interaction exhibited the strongest dose-response association (OR 8.54 [95% CI 1.59-45.9] for highest respiratory burden). CONCLUSION: This study identified novel respiratory risk factors and gene-respiratory endotypes for RA, which may be useful for RA prevention, diagnosis, and treatment.
Serological Stratification by Anti-Ro52 and Anti-Ro60 Profiles Reveals Distinct Systemic Phenotypes in Primary Sjögren's Disease.
Zhang Q, Zhang L, Lv L … +5 more , Chen D, Yang Z, Yi W, Jia Z, Feng X
Semin Arthritis Rheum · 2026 Apr · PMID 41707292 · Publisher ↗
BACKGROUND: Anti-Ro52 and anti-Ro60 antibodies are key serological markers for primary Sjögren's disease (pSjD), yet their association with specific clinical phenotypes remains unclear. This study aimed to define the pre...
BACKGROUND: Anti-Ro52 and anti-Ro60 antibodies are key serological markers for primary Sjögren's disease (pSjD), yet their association with specific clinical phenotypes remains unclear. This study aimed to define the predictive value of anti-Ro profiles for systemic involvement in pSjD. METHODS: In this retrospective study of 725 pSjD patients, we categorized patients into four subgroups based on their anti-Ro52/Ro60 status. Multivariable logistic regression, adjusted for confounders via LASSO, assessed independent associations. Relative excess risk due to interaction (RERI), attributable proportion of interaction (AP) and synergy index (SI) were calculated to determine the additive interaction between anti-Ro52 and anti-Ro60. RESULTS: The cohort consisted of 21.5% Ro52-Ro60-, 17.7% Ro52+Ro60-, 10.2% Ro52-Ro60+, and 50.6% Ro52+Ro60+ patients. Anti-Ro52 positive groups (Ro52+Ro60- and Ro52+Ro60+) exhibited significantly higher ESSDAI scores. After adjustment, the Ro52+Ro60+ profile was independently associated with renal involvement (OR=5.53, 95%CI 2.56-11.97, p<0.001), cutaneous involvement (OR=2.49, 95%CI 1.08-5.75, p=0.032), hyperglobulinemia (OR=5.19, 95%CI 2.96-9.10, p<0.001), and low complement levels (OR=1.70, 95%CI 1.07-2.71, p=0.025). In contrast, the Ro52+Ro60- profile was specifically linked to interstitial lung disease (ILD) (OR=4.17, 95%CI 2.33-7.46, p<0.001). A significant synergistic interaction between anti-Ro52 and anti-Ro60 was identified for hyperglobulinemia (adjusted RERI=3.00, 95%CI 0.87-5.14; AP=0.58, 95%CI 0.31-0.84; SI=3.52, 95CI 1.04-11.94). CONCLUSIONS: Anti-Ro52 and anti-Ro60 profiles delineate distinct clinical subsets of pSjD. Anti-Ro52 positivity is associated with greater disease severity, while double positivity defines a unique subgroup with multi-organ involvement and immune hyperactivation, highlighting the clinical utility of comprehensive anti-Ro testing.
Stroke characteristics in giant cell arteritis and Takayasu arteritis: A multicenter retrospective cohort study of 108 patients.
Dhrif O, Caudron C, Parreau S … +18 more , Liozon E, Mirouse A, Alexandra JF, Sailler L, Velia C, Groh M, de Boysson H, Ebbo M, Comarmond C, Durel CA, Woessner J, Jarrot PA, Didier K, Goulabchand R, Cacoub P, Bonnotte B, Saadoun D, Samson M
Semin Arthritis Rheum · 2026 Apr · PMID 41702324 · Publisher ↗
INTRODUCTION: Stroke is an uncommon but pivotal prognostic factor in giant cell arteritis (GCA) and Takayasu arteritis (TAK). While both conditions are large vessel vasculitis stroke characteristics may differ between th...
INTRODUCTION: Stroke is an uncommon but pivotal prognostic factor in giant cell arteritis (GCA) and Takayasu arteritis (TAK). While both conditions are large vessel vasculitis stroke characteristics may differ between them, with potential implications for diagnosis and acute management. This study aimed to compare the epidemiological, clinical, and prognostic features of stroke in GCA and TAK. METHODS: We conducted a multicenter retrospective cohort study including patients who met the ACR/EULAR 2022 classification criteria for GCA or TAK and experienced at least one imaging-confirmed stroke. Patients with transient ischemic attacks, strokes occurring after the age of fifty in TAK, or strokes secondary to atrial fibrillation were excluded. RESULTS: A total of 108 patients were analyzed (68 GCA, 40 TAK). The female-to-male ratio was 0.78 in GCA and 5.2 in TAK (p<0.001). Stroke occurred at a mean age of 75±12 years in GCA and 35±11 years in TAK (p<0.001). Hypertension (64.7% vs. 32.4%, p=0.003) and dyslipidemia (36.8% vs. 8.8%, p=0.002) were more frequent in GCA. Cerebellar syndrome (29.4% vs. 0%, p=0.001), cranial nerve involvement (19.7% vs. 0%, p=0.017), and sensory deficits (55.9% vs. 18.4%, p<0.001) were more frequent in GCA. Stroke involved the vertebrobasilar territory in 75% of GCA vs. 20.5% of TAK (p<0.001) and the carotid territory in 35.3% of GCA vs. 79.5% of TAK (p<0.001). Vascular intervention was required in 41% of TAK vs. 6% of GCA (p<0.001). CONCLUSION: Stroke presentation differs between GCA and TAK, with predominant vertebrobasilar involvement in GCA. Carotid involvement is more frequent in TAK and often requires vascular procedures. These differences are crucial for appropriate management.
Definitions and online reliability assessment of elementary ultrasound lesions in Takayasu arteritis: a study from the OMERACT Ultrasound Working Group.
Tomelleri A, Reider SJ, Dejaco C … +52 more , Schmidt WA, Ponte C, Hocevar A, Águeda AF, Alibaz-Oner F, Appenzeller S, Aschwanden M, Bastian H, Bosch P, Camellino D, Casteleyn V, Chrysidis S, Daikeler T, De Miguel E, Diamantopoulos AP, Filippou G, Goel R, Hanova P, Hartung W, Ikeda K, Inanc N, Jousse-Joulin S, Juche A, Karalilova R, Keller KK, Kjær SG, Kohler MJ, Koster MJ, Macchioni P, Mackie SL, Milchert M, Misra DP, Molina-Collada J, Monti S, Nakagomi D, Naredo E, Nielsen BD, Ogasawara M, Roth J, Schäfer VS, Seitz L, Seitz P, Shumnalieva R, Terslev L, van der Geest KSM, Vreju FA, D'Agostino MA, Keen HI, Mandl P, Pineda C, Duftner C, Bond M
Semin Arthritis Rheum · 2026 Apr · PMID 41702323 · Publisher ↗
OBJECTIVES: Reliable tools for monitoring disease activity in Takayasu arteritis (TAK) are lacking, and ultrasonography (US) may represent a valuable option. This study aimed to: 1) develop consensus-based definitions fo...
OBJECTIVES: Reliable tools for monitoring disease activity in Takayasu arteritis (TAK) are lacking, and ultrasonography (US) may represent a valuable option. This study aimed to: 1) develop consensus-based definitions for key US lesions in TAK; 2) identify the relevant arterial segments to include in an US-based score; 3) assess inter- and intra-rater reliability of the definitions in a web-based image analysis and scoring exercise. METHODS: A Delphi survey was conducted among members of the OMERACT Ultrasound Working Group to agree upon the definitions of key elementary US lesions and arterial segments to be included. A subsequent web-based reliability exercise included US images from TAK patients and healthy controls depicting the consensual lesions. Experts scored each image in two separate rounds. Inter-rater and intra-rater reliability were assessed using Fleiss' and Cohen's kappa (κ), respectively. RESULTS: Three Delphi rounds were completed with 47, 46, and 43 experts respectively. Consensus was reached on three lesions ('macaroni sign', stenosis, occlusion) and seven arterial segments (bilateral common carotid, subclavian, axillary arteries, abdominal aorta). Forty-five experts completed the reliability exercise. Inter-rater reliability was moderate to good (κ = 0.47-0.64), with the highest agreement for the 'macaroni sign' in the carotid artery (κ = 0.73). Intra-rater reliability was good (κ = 0.72-0.79), with lower agreement for stenosis and occlusion in the abdominal aorta. CONCLUSIONS: This OMERACT initiative established consensus-based definitions for US lesions in TAK and identified key relevant arterial segments, providing a reliable basis for the development of a standardized US composite score.
Colchicine prophylaxis efficacy in PFAPA syndrome: A comparative cohort study.
Kasem AliSliman R, Regev S, Ghanim B … +1 more , Hamad Saied M
Semin Arthritis Rheum · 2026 Apr · PMID 41691734 · Publisher ↗
BACKGROUND: PFAPA (periodic fever, aphthous stomatitis, pharyngitis, adenitis) syndrome is the most common periodic fever disorder in children, causing recurrent debilitating episodes that impose a substantial burden on...
BACKGROUND: PFAPA (periodic fever, aphthous stomatitis, pharyngitis, adenitis) syndrome is the most common periodic fever disorder in children, causing recurrent debilitating episodes that impose a substantial burden on children and their families. Current therapeutic approaches primarily rely on corticosteroid administration, which provides rapid symptom resolution but fails to address the underlying inflammatory cascade, prevent future attacks, and carries the risk of side effects. OBJECTIVES: To determine the therapeutic efficacy of colchicine prophylaxis in reducing attack frequency and extending disease-free intervals in PFAPA patients, compared to standard of care management alone. METHODS: This retrospective cohort study included 55 pediatric PFAPA patients, 15 receiving colchicine prophylaxis, and 40 controls managed with standard care alone. The primary outcome was the change in inter-attack interval duration from baseline study completion. Secondary analyses examined treatment response by FMF genetic status and survival analysis for time to next attack. RESULTS: Both groups showed comparable baseline characteristics, except higher FMF mutation prevalence in the colchicine group (73.3% vs. 27.5%, P = 0.002). Patients receiving colchicine experienced a dramatic improvement in inter-attack intervals (median change: 60 days, IQR: 51) compared with controls (median change: 0 days, IQR: 0; P < 0.001). Colchicine's therapeutic benefit was consistent regardless of FMF genetic status. CONCLUSIONS: Colchicine prophylaxis significantly reduces PFAPA attack frequency, with therapeutic benefits that are independent of FMF genetic status. These findings support colchicine as an effective first-line prophylactic treatment for PFAPA patients with frequent episodes or families concerned about frequent steroid use, representing a paradigm shift from reactive to preventive management.
Gastric disease in systemic sclerosis: Spectrum, challenges, and insights from a systematic literature review.
Anderton RM, Zhu A, Ayla A … +7 more , Chavez M, Mayer A, Koym K, Guillen-Del-Castillo A, Alcala-Gonzalez LG, Hughes M, McMahan ZH
Semin Arthritis Rheum · 2026 Apr · PMID 41687407 · Publisher ↗
OBJECTIVE: Gastric complications in systemic sclerosis (SSc) are common, clinically diverse, and often overlooked, despite their profound impact on patient quality of life. This review synthesizes current evidence on pre...
OBJECTIVE: Gastric complications in systemic sclerosis (SSc) are common, clinically diverse, and often overlooked, despite their profound impact on patient quality of life. This review synthesizes current evidence on prevalence, clinical relevance, and diagnostic strategies, while identifying key gaps and proposing priorities to advance care and research. METHODS: A systematic review was conducted per PRISMA guidelines and registered with PROSPERO. MEDLINE, EMBASE, and Web of Science were systematically searched (September 2024). Included studies addressed gastric manifestations in SSc, such as dysmotility, gastric antral vascular ectasia (GAVE), mucosal abnormalities, and/or Helicobacter pylori, and reported on prevalence, clinical impact, or diagnostic approaches. RESULTS: Of 123 full-text articles, 37 met our specified inclusion criteria. Gastric dysmotility was frequent, with delayed emptying in 18-64 % and bradygastria in 12-70 %. GAVE prevalence ranged from 0 to 22.3 % and was negatively associated with anti-topoisomerase-I and variably associated with anti-RNA polymerase III antibodies. Mucosal abnormalities (e.g., gastritis, ulcers, cancer) were common but inconsistently defined. Helicobacter pylori prevalence varied widely (10-78 %), with lower detection via biopsy or breath testing than serology. Associations between objective findings and patient-reported outcomes (PROs) were inconsistent and underexplored; data on gastric-specific mortality were limited. CONCLUSION: Gastric disease in SSc is underrecognized, yet clinically significant. Progress necessitates standardized diagnostics (scintigraphy, breath tests, electrogastrography), validated patient-reported outcomes (PROs), and longitudinal studies to better define disease burden, optimize screening, and guide targeted therapies that improve outcomes and quality of life in SSc.
From Aortitis to Sweet's: The Immune Spectrum of G-CSF Adverse Events.
de Carvalho JF, Caldas CAM
Semin Arthritis Rheum · 2026 Apr · PMID 41655516 · Publisher ↗
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) and its PEGylated formulation (pegfilgrastim) are indispensable for preventing chemotherapy-induced neutropenia and for stem-cell mobilization. Beyond hematopoies...
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) and its PEGylated formulation (pegfilgrastim) are indispensable for preventing chemotherapy-induced neutropenia and for stem-cell mobilization. Beyond hematopoiesis, G-CSF modulates innate/adaptive immunity and may precipitate immune-mediated events in susceptible hosts. Clinical signals span large-vessel vasculitis/aortitis and non-vascular neutrophil-dominant phenotypes, yet timing, spectrum, and management remain variably characterized. OBJECTIVE: To identify and synthesize primary clinical reports of autoimmune/rheumatic disease triggered or exacerbated by exogenous G-CSF (filgrastim or pegfilgrastim), describing phenotypes, latency, management, outcomes, and implications for practice. METHODS: We performed a narrative review of primary clinical studies, including observational cohorts and case reports or short case series, identified through targeted searches of PubMed/MEDLINE, Scopus, and Embase, complemented by investigator-curated references. Eligible reports described autoimmune, inflammatory, or rheumatic manifestations occurring after exposure to exogenous G-CSF. Predefined phenotypes included large-vessel vasculitis/aortitis; neutrophilic dermatoses (e.g., Sweet's syndrome, neutrophilic dermatosis of the dorsal hands); cutaneous small-vessel vasculitis; inflammatory or crystal arthritis (e.g., calcium pyrophosphate deposition disease); pulmonary inflammatory injury (e.g., diffuse alveolar hemorrhage); and clear flares of established autoimmune disease. Narrative or mechanistic reviews and trials of GM-CSF pathway blockade were excluded from qualitative synthesis. RESULTS: Twenty-four studies met inclusion criteria: two observational cohorts and twenty-two single-patient reports/short series. Cohorts quantified a low but reproducible burden of pegfilgrastim-associated aortitis, with stereotyped involvement of the aortic arch/proximal branches and typical latency of 7-15 days. Case-level data confirmed marked elevation of acute phase reactants, usually negative autoantibodies, favorable outcomes after G-CSF withdrawal with or without short glucocorticoid courses, and recurrence/migration on re-exposure. Non-vascular events clustered earlier (2-7 days) and included biopsy-proven Sweet's/NDDH, leukocytoclastic vasculitis, CPPD flares, and rare diffuse alveolar hemorrhage; granulomatous dermatitis and perioperative pyoderma gangrenosum were also observed. Re-exposure information suggested phenotype-specific risk: recurrent CPPD with pegfilgrastim was mitigated by switching to short-acting filgrastim; selected limited aortitis resolved without steroids; refractory aortitis responded to IL-6 blockade, enabling uninterrupted chemotherapy. CONCLUSIONS: Exogenous G-CSF can precipitate a coherent spectrum of immune-mediated toxicity with distinct, clinically actionable timing windows: vascular events peak 7-15 days after pegfilgrastim, whereas cutaneous, articular, and pulmonary manifestations arise within 2-7 days. Recognition hinges on temporal linkage, imaging/histology, and exclusion of mimics. Management is phenotype-aware-drug withdrawal ± short glucocorticoids, formulation switching for CPPD, and targeted IL-6 blockade in selected refractory aortitis-allowing preservation of hematologic benefits while minimizing immune toxicity. Prospective surveillance and structured re-exposure studies (including formulation tailoring) are priorities to move from signal detection to prevention.
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