OBJECTIVES:Indirect immunofluorescence (IIF) and CTD screen exhibit divergent performance characteristics for antinuclear antibody (ANA) detection, yet their relative utility across different clinical contexts remains poorly defined. We compared the diagnostic performance of ANA-IIF and CTD screen assay across stratified levels of pre-test probability. METHODS:We evaluated 822 consecutive patients referred to a specialist rheumatology service, tested in parallel by both ANA-IIF and CTD screen. Patients were stratified by pre-test probability based on clinical, laboratory, and imaging risk factors: high risk (≥2 major factors), moderate risk (1 major factor), and low risk (minor factors only). Primary outcome was CTD diagnosis according to international classification criteria. Diagnostic accuracy parameters, including sensitivity, specificity, predictive values, and likelihood ratios, were calculated for each risk stratum. RESULTS:ANA-IIF demonstrated higher sensitivity than CTD screen across all risk groups (0.76-1.00 vs. 0.76-0.83), whilst CTD screen exhibited superior specificity (0.89-0.96 vs. 0.43-0.81). In high-risk patients (CTD prevalence 47.1 %), both methods achieved clinically acceptable performance. In low-risk patients (CTD prevalence 12.9 %), CTD screen's enhanced specificity yielded markedly superior diagnostic accuracy (0.88 vs. 0.61-0.76 for ANA-IIF), with higher positive predictive value. Discordant ANA-IIF-positive/CTD screen-negative CTD cases comprised predominantly mild undifferentiated disease or patients with clinically recognisable features mandating specialist referral regardless of ANA results. CONCLUSIONS:Optimal ANA screening methodology depends on pre-test probability. ANA-IIF remains preferred in high-risk populations, whilst CTD screen provides superior performance in low-risk settings through reduced false-positive rates without clinically significant diagnostic loss.

Sjögren's disease (SjD) is a systemic autoimmune condition for which reliable diagnostic and stratification biomarkers are still lacking. Several molecules have been implicated in its pathogenesis, and this study aimed to evaluate their potential as biomarkers in a monocentric cohort of SjD patients. Sera from 40 SjD patients (2016 ACR/EULAR criteria) and 41 matched controls were analyzed for 23 soluble inflammatory mediators using a Luminex® multiplex immunoassay. Clinical and laboratory correlations were examined, and multivariate logistic regression was performed. Compared with controls, SjD patients had significantly higher levels of IL-15 (11.52 ± 24.95 vs. 1.37 ± 1.26 pg/ml, P = 0.0009), monocyte chemoattractant protein (MCP)-1 (683.6 ± 1127 vs. 654.8 ± 608.9 pg/ml, P = 0.0203), TNFRII (8588 ± 2889 vs. 5505 ± 1007 pg/ml, P < 0.0001), and MMP-8 (6382 ± 12,697 vs. 6247 ± 6950 pg/ml, P = 0.0141), while IL-1RII was reduced (6267 ± 1699 vs. 8514 ± 2255 pg/ml, P < 0.0001). IL-15 correlated with hypergammaglobulinemia and monoclonal component, MCP-1 with focus score and sicca severity, and IL-1RII with anti-SSB positivity. Logistic regression identified TNFRII and IL-1RII as the strongest independent predictors of SjD (AUC = 0.89). This study supports the association of IL-15, TNFRII, and MCP-1 with immune dysregulation in SjD and highlights MMP-8 and IL-1RII as promising serological biomarkers. Validation in larger, longitudinal cohorts is warranted.

Rheumatoid arthritis (RA) patients face increased cardiovascular (CV) risk, yet existing 10-year estimation tools often underperform. This study evaluated whether unsupervised machine learning (uML) clustering can identify distinct RA patient phenotypes with varying major cardiovascular events (MACE) potentially improving risk stratification. A cross-sectional, multi-center cohort of RA patients meeting the 2010 ACR/EULAR classification criteria and without prior CV events was enrolled in January 2019 and followed-up for MACE incidence over 5 years. Clinical and demographic data, including traditional CV risk factors and SCORE2 estimates, were collected. Factor Analysis of Mixed Data (FAMD), a generalization of principal component analysis for mixed data types, was applied in Python (ver.3.9) using Prince (ver.0.7.1). Missing data observations were excluded. Bootstrapped eigenvalue distribution determined the number of FAMD components for clustering, followed by Hierarchical Clustering on Principal Components using Ward’s criterion and Euclidean distance. An XGBoost model assessed feature importance, while ANOVA and Chi-square tests evaluated cluster differences. Among 951 RA patients (mean age 61.8 ± 10.5 years; 81.1

OBJECTIVES:To assess the long-term outcomes and prognostic factors of patients presenting with all-cause mixed cryoglobulinaemia vasculitis (CryoVas). METHODS:A European multicentre cohort study (EuroCryo) of 1294 patients presenting with all-cause CryoVas. RESULTS:The main aetiology for CryoVas was Hepatitis C Virus ( HCV) with 469 (36%) cases, followed by essential forms (n = 344, 26%) and autoimmune conditions (n = 302, 23%), with Sjögren's disease being the most common (n = 268, 21%). Over a median follow-up of 2.8 years, a total of 558 CryoVas patients experienced 661 severe events, notably 221 relapses, 52 severe infections and 45 lymphomas. The multivariable model for event-free survival retained a post-2014 diagnosis, male sex, older age, low C4 levels, positive Rheumatoid Factor and higher baseline creatinine levels as poor prognostic factors; HCV aetiology was protective. Factors associated with the occurrence of lymphoma were a post-2014 diagnosis, autoimmune aetiology, fever, fatigue and low C4 levels. CONCLUSION:HCV was for long considered a poor prognosis factor in CryoVas, and now those secondary to autoimmune conditions seem to evolve with a more severe course, notably carrying a higher lymphoma risk.

OBJECTIVE:Sjögren disease (SjD) is a systemic autoimmune disease characterized by increased risk of B-cell non-Hodgkin lymphoma. Although cryoglobulinemia and serum monoclonal component (MC) are well-recognized paraproteinemias in SjD, no large-scale study has directly compared their isolated and combined impact on phenotype and lymphoproliferative risk. METHODS:A retrospective, multicenter, cross-sectional study was conducted within the Italian GRISS registry. Patients with SjD were stratified into four groups: isolated monoclonal gammopathy (MC-alone), isolated cryoglobulinemia (CRYO-alone), both (MC+CRYO), or neither (controls). Demographics, lymphoma history, ever-documented ClinESSDAI domains, and laboratory lymphoproliferative risk-related markers were analyzed. Primary and secondary outcomes assessed lymphoma diagnosis and the distribution of laboratory lymphoproliferative risk-related markers and ClinESSDAI domains across groups, with associations tested using logistic regression adjusted for confounders. RESULTS:1202 SjD patients were enrolled: 58 (4.83%) in the MC-alone, 32 (2.66%) in the CRYO-alone, 35 (2.91%) in the MC+CRYO, and 1077 (89.60%) controls. Compared with controls, only the MC+CRYO group showed significant association with lymphoma (OR 6.30, 95%CI 2.66-14.92; p < 0.001), while MC-alone and CRYO-alone were not associated. Cryoglobulinemia, alone or combined with MC, correlated with laboratory lymphoproliferative risk-related markers such as rheumatoid factor (p < 0.001) and low C4 (p < 0.001), and with ClinESSDAI vasculitic features (cutaneous [p < 0.001], renal [p < 0.05], PNS [p < 0.001]). The MC+CRYO group additionally displayed a lymphoproliferative phenotype correlating with constitutional (p < 0.05), glandular (p < 0.05), hematological (p < 0.001), and lymphadenopathy (p < 0.001) domains. CONCLUSION:Cryoglobulinemia in SjD associates with vasculitic disease activity, whereas the coexistence of serum MC and cryoglobulins identifies a distinct, high-risk subset characterized by advanced B-cell expansion and increased lymphoma susceptibility.

ObjectiveBehçet’s disease (BD) may initially manifest solely with mucocutaneous involvement. This study aimed to identify demographic and clinical factors associated with subsequent intestinal involvement in patients presenting exclusively with mucocutaneous manifestations during early disease stages.MethodsData were obtained from the International AutoInflammatory Disease Alliance Network registry dedicated to BD; a Bayesian statistical approach was employed to address the limited sample size resulting from subgroup stratifications.ResultsIn total, 328 BD patients with exclusively mucocutaneous onset were enrolled; of these, 46 (14%) developed intestinal involvement over time. The risk of ocular involvement was higher among patients with intestinal manifestations (OR: 3.02, 95% CrI: 1.24–6.08; posterior probability: 99.3%). Minor aphthous ulcers without major aphthosis were protective towards intestinal involvement (OR: 0.47, 95% CrI: 0.22–0.98; posterior probability: 97.98%). Conversely, major aphthous ulcers increased the risk (OR: 3.25, 95% CrI: 1.50–7.02; posterior probability: 99.7%), along with the combination of oral major aphthosis with: i) genital aphthosis (OR = 2.77, 95%CrI: 1.14-6.58; posterior probability: 98.45%); ii) pseudofolliculitis (OR = 3.18, 95%CrI: 1.15-8.33; posterior probability: 98.72%); iii) genital aphthosis plus pseudofolliculitis (OR = 5.22, 95%CrI: 1.71-16.35; posterior probability of 99.77%). Pseudofolliculitis plus cutaneous manifestations other than erythema nodosum were protective against intestinal involvement (OR = 0.01, 95%CrI: 0.0-0.98; posterior probability: 97.55%).ConclusionMajor aphthosis was the strongest factor associated with intestinal involvement in BD patients initially presenting with mucocutaneous symptoms only. In such patients, intestinal involvement correlated with increased risk of ocular inflammation.

OBJECTIVES:To investigate cutaneous manifestations in Still's disease patients, evaluating any correlation with ethnic origin, age at disease onset, disease patterns, occurrence of macrophage activation syndrome (MAS) and systemic activity scores. METHODS:Data were retrospectively drawn from the International AutoInflammatory Disease Alliance (AIDA) Network Registry dedicated to Still's disease. RESULTS:A total of 518 patients (41.3% males) were enrolled. Salmon-coloured evanescent skin rash (n = 304, 63.9%), macules (n = 40, 7.7%), urticarial eruptions (n = 31, 5.9%), erythema (n = 27, 5.2%) and persistent pruritic papules and plaques (PPPP) (n = 25, 4.8%) accounted for the most frequent skin manifestations observed in Still's disease. Overall, atypical skin rash were described in 110 (21.2%) patients. Salmon-coloured evanescent skin rash and pruritus were more common among patients aged <16 years compared with patients aged 16-60 (P = 0.002 and P = 0.008, respectively). Pruritus was significantly more frequent among White than among Arab patients (P = 0.008) and in polycyclic vs monocyclic course (P = 0.049). Hispanics showed a significantly higher rate of atypical skin manifestations compared with Arabs (P = 0.036) and White (P = 0.036). Also, macules were more frequent among Hispanics than White (P = 0.027), while PPPP was more frequent among Hispanics than Arabs (P = 0.023) and White (P = 0.002). Salmon-coloured evanescent skin rash was significantly more frequent among patients with a systemic activity score ≥7 (P < 0.001). CONCLUSION:The present study enhances dermatologists' awareness of the diverse cutaneous lesions that may represent heterogeneous manifestations of Still's disease, shedding new light on the difference related to the age at disease onset, the patients' ethnic origin and the severity of the disease.

Musculoskeletal manifestations, particularly spondyloarthritis (SpA), represent the most frequent extraintestinal manifestations of inflammatory bowel disease (IBD). The coexistence of intestinal and articular inflammation poses diagnostic and therapeutic challenges requiring coordinated multidisciplinary care. Axial SpA occurs in 6-62% of IBD patients, while peripheral arthritis affects up to one third of patients. The temporal relationship between intestinal and joint disease is variable, and musculoskeletal symptoms may often precede IBD diagnosis. Shared pathogenic mechanisms include genetic susceptibility, dysregulated immune pathways, intestinal barrier dysfunction and aberrant lymphocyte trafficking between gut and synovium. Diagnostic delay remains substantial and serologic biomarkers have limitations. Therapeutic algorithms must consider both intestinal and articular disease activity, with newer biologics and targeted therapies requiring careful selection due to differential efficacy across disease domains. Multidisciplinary care models improve diagnostic accuracy, clinical outcomes, and patient satisfaction. This narrative review summarizes and integrates current evidence on epidemiology, pathophysiology, clinical features, diagnostic strategies and management of IBD-associated axial and peripheral SpA.

Idiopathic inflammatory myopathies (IIM) are systemic autoimmune diseases that include dermatomyositis, polymyositis, antisynthetase syndrome, and immune-mediated necrotizing myopathy in both adult and juvenile populations. Interstitial lung disease (ILD) is a common and serious complication of IIM, with a highly variable clinical course ranging from indolent disease to rapidly progressive respiratory failure, often influenced by underlying myositis-specific autoantibody profiles. Despite the substantial morbidity and mortality associated with IIM-ILD in both adults and children, high-quality evidence to guide clinical management remains limited. A major barrier to progress in this field is the lack of standardized disease nomenclature and uniform diagnostic or classification criteria, which hampers cohort development, limits comparability across studies, and restricts generalizability of findings. To address this gap, we will conduct a systematic review to inform a consensus-based disease definition for adult and juvenile IIM-ILD, with detailed methodology outlined in this protocol. This review will not evaluate prognosis, treatment, or clinical outcomes, but instead focus exclusively on how IIM-ILD is defined and operationalized across studies. Following PRISMA 2020 statement and Cochrane methodology, we will search PubMed, EMBASE, Scopus, Cochrane Systematic Reviews, and Cochrane Central from inception to June 30, 2025, using a ‘‘Peer Review of Electronic Search Strategies (PRESS)’’—validated strategy. Eligible studies will include randomized controlled trials (RCTs), cohort and case–control studies, systematic reviews, meta-analyses, guidelines, and consensus statements explicitly reporting IIM-ILD definitions in human participants of all ages. Study selection will be performed in Covidence using predefined criteria. Data extraction will capture case definitions, classification criteria, diagnostic methods, ILD patterns, autoantibody profiles, and study characteristics. Quantitative synthesis will summarize the frequency and components of definitions where possible; otherwise, a structured narrative synthesis will be performed. Our systematic review protocol is the first comprehensive attempt at synthesizing the highly heterogenous disease nomenclature currently employed in adult and juvenile IIM-ILD literature. Findings will map areas of agreement and inconsistency in existing definitions, forming an evidence base for subsequent consensus processes, such as Delphi, to establish standardized nomenclature. Harmonized definitions are expected to improve research reproducibility, facilitate multicentric collaboration, and improve patient stratification in clinical practice and trials. PROSPERO ID: 1129967.

OBJECTIVES:To assess, for the first time, macrovascular, medium-calibre vessel, and microvascular damage in Sjögren's disease (SjD) using carotid greyscale ultrasound (GSUS), retrobulbar colour Doppler ophthalmic artery (OA) ultrasound (RCDUS), and static retinal vessel analysis (SRVA). Additionally, to evaluate associations of these markers with cardiovascular (CV) risk factors, patient- and disease-related characteristics. METHODS:GSUS of the common carotid arteries was performed to measure carotid intima-media thickness (cIMT) and evaluate plaque burden. RCDUS assessed OA flow velocity integral (FVI), resistive, and pulsatility indices (RI, PI). SRVA quantified retinal microvasculature using central retinal arteriolar, venular equivalents (CRAE, CRVE), and the arteriovenous ratio (AVR). Imaging findings were compared between patients with SjD and healthy controls and analysed in relation to clinical parameters. RESULTS:130 SjD patients and 100 controls were included. SjD patients showed significantly higher cIMT (padj=0.003), OA-RI (padj=0.003) and -PI (padj<0.001), as well as lower OA-FVI (padj=0.012) and CRAE (padj=0.013) compared with controls. Higher OA-RI and -PI correlated with higher disease activity (ESSDAI: both; rho=0.324, p = 0.006), and impaired renal function (rho=-0.461, p < 0.001 and rho=-0.370, p = 0.002, respectively). OA-RI associated positively with age (rho=0.435, p < 0.001) and inversely with lung carbon monoxide diffusion (r=-0.342, p = 0.019). Lower CRAE correlated with higher mean arterial pressure (r =-0.378, p < 0.001), CRP (rho= -0.215, p = 0.046), ANA titre (rho=-0.268, p = 0.016), and disease activity (ESSDAI: rho=-0.273, p = 0.011). CONCLUSIONS:In this first comprehensive study of CV surrogate markers in SjD, patients exhibited vascular alterations across multiple vascular beds, indicating systemic vascular involvement and a possible link to increased cardiovascular and cerebrovascular risk.

Nanoparticle-based strategies offer a promising tool for inducing antigen-specific immune tolerance across various autoimmune conditions, by acting as master switch to turn-off the autoimmune response. Building on our previous work demonstrating the therapeutic potential of plant-made nanoparticles in rheumatoid arthritis, we present a systematic evaluation of key parameters, including dosing regimen, route of administration, and immunization schedule, to optimize both efficacy and safety. We developed virus-based nanomaterials expressing Tomato Bushy Stunt Virus (TBSV) nanoparticles engineered to display the immunodominant Liprin-1 peptide in the Nicotiana benthamiana plant platform. The mechanisms responsible for the observed protective effects against rheumatoid arthritis were also investigated. Our findings highlight the critical role of repeated intravenous administration and precise dosing in promoting regulatory T cell (Treg) induction and cytokine modulation. Furthermore, we dissected the individual contributions of the Liprin-1 peptide and the viral capsid scaffold in driving immune tolerance. These results support the potential of plant-derived nanoparticles as a versatile and effective platform for antigen-specific immunotherapy, with rheumatoid arthritis serving as a proof-of-concept model for broader applications in the field of autoimmunity. ### Competing Interest Statement LA and RZ were founders of Dimante SB srl. AR, EG and RZ are employees of Diamante SB srl. The work here described has been patented. AM, JM, JB, NS and SF are part of the scientific advisory board of Diamante SB srl. The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. European Innovation Council, https://ror.org/05cx8cy07, 101189019

OBJECTIVES:This study aimed to compare different treatment strategies for rheumatoid arthritis (RA) patients following inadequate response to initial methotrexate (MTX) therapy, evaluating clinical outcomes, tolerability profiles, and factors influencing treatment decisions in real-world clinical practice. METHODS:We retrospectively analysed 239 MTX non-responders from health records. Patients were grouped based on subsequent treatment: direct switch to biologic/targeted synthetic DMARDs (b/tsDMARDs) (n=45) or MTX dose escalation (n=194). Those failing dose escalation were further stratified into leflunomide (LEF) (n=37) or b/tsDMARD (n=57) groups. Treatment efficacy was assessed using modified EULAR Boolean criteria (3V-remission) at 6-month intervals. RESULTS:While direct b/tsDMARD initiation achieved higher 3V-remission rates than MTX dose escalation (62.2% vs. 35.0%, p<0.001), MTX dose optimisation still enabled remission in over one-third of patients. Similarly, among MTX dose escalation non-responders, LEF therapy achieved 3V-remission in 43.2% of patients, comparable to b/tsDMARDs (50.9%, p=0.469), despite higher discontinuation rates (21.6% vs. 1.8%). Importantly, sequential csDMARD optimisation did not compromise subsequent b/tsDMARD responsiveness, with similar remission rates regardless of prior treatment exposure (62.2% after initial MTX, 50.9% post-dose escalation, 46.1% post-LEF, p=0.417). CONCLUSIONS:While b/tsDMARDs demonstrated superior efficacy and tolerability, approximately one-third of patients achieved remission through MTX dose optimisation, possibly reflecting suboptimal initial dosing. Importantly, prior csDMARD optimisation did not compromise subsequent b/tsDMARD responsiveness. These findings underscore the importance of appropriate initial MTX dosing, while indicating that csDMARD optimisation before b/tsDMARD initiation should be considered, given the predominantly mild nature of observed adverse events.

Janus kinase (JAK) inhibitors have emerged as a transformative therapeutic class across autoimmune diseases by targeting multiple cytokine networks implicated in inflammation and fibrosis. Beyond inflammatory arthritis, increasing evidence supports their potential efficacy in connective tissue diseases such as idiopathic inflammatory myopathies, systemic sclerosis, primary Sjögren's disease, and systemic lupus erythematosus. Through modulation of type I/II interferon and interleukin signalling, JAK inhibition exerts broad anti-inflammatory and antifibrotic effects, translating into clinical improvements in cutaneous, articular and pulmonary domains. Early clinical trials and real-world data confirm meaningful responses in refractory disease, though randomized evidence remains limited. Overall, JAK inhibitors represent a promising, mechanistically grounded option for systemic autoimmune diseases, with ongoing studies expected to refine selectivity, indications and long-term safety profiles.

OBJECTIVE:International guidelines recommend early combination of standard therapy with innovative agents in lupus nephritis (LN) to prevent kidney damage. Whether this accelerates renal response is unclear. We aimed to compare renal response trajectories, predictors and glucocorticoid (GC) burden in LN patients receiving early belimumab plus standard-of-care (SoC) vs SoC alone. METHODS:Consecutive adult patients with biopsy-proven LN treated with belimumab plus SoC as initial therapy were enrolled from Italian lupus referral centres and compared with a historical SoC cohort (1990-2016). Data were collected at baseline and during follow-up. Propensity score matching based on baseline proteinuria, estimated glomerular filtration rate, standard initial treatment and histological class led to comparable groups. Complete renal response (CRR) was defined per 2019 EULAR/EDTA. Cox regression was used to assess predictors. RESULTS:Ninety-one belimumab patients were matched to 91 SoC patients. At 6 months, CRR was higher in the belimumab group (35.9% vs 16.5%, odds ratio [95% CI]: 2.81 [1.30, 6.29], P = 0.005), while response rates at 12 months were similar (P = 0.87). Time-to-CRR was shorter with belimumab (median [interquartile range] 5.64 [4.08, 7.80] vs 7.92 [5.28, 11.04] months, P < 0.01). At CRR, GC dose was lower in the belimumab group (5 [5-15] vs 15 [10-20] mg/day, P = 0.018). Independent predictors of earlier CRR were baseline proteinuria (hazard ratio per g/24 h increase [95% CI]: 0.89 [0.80, 0.98], P = 0.019) and belimumab use (1.70 [1.11, 2.62], P = 0.016). CONCLUSION:Early belimumab combination therapy accelerates CRR and reduces GC exposure. Achieving early CRR with lower GC is a key target to limit kidney and GC-related damage, supporting early belimumab integration in LN management.

Colchicine is an ancient drug that remains a cornerstone in the management of crystal-induced inflammatory diseases, particularly gout and calcium pyrophosphate crystal disease (CPPD). Its clinical use is supported by well-established pharmacological and mechanistic evidences, mainly derived from experimental studies. Colchicine interferes with microtubule-dependent cellular functions, inhibits neutrophil activation, and modulates NLRP3 inflammasome signalling, resulting in reduced interleukin-1β production. In addition, colchicine exerts pleiotropic anti-inflammatory effects that extend beyond crystal synovitis, including modulation of platelet-leukocyte interactions and vascular inflammation. Owing to its narrow therapeutic index, low-dose regimens and careful attention to drug-drug interactions are essential. This narrative review summarises the pharmacology, mechanisms of action, and clinical applications of colchicine in rheumatic disorders, particularly gout and CPPD, and its expanding use in cardiovascular diseases, dermatology, and other inflammatory disorders.

Objectives To evaluate whether early canakinumab initiation may provide treatment advantages in Still’s disease (SD) patients, particularly in terms of therapy discontinuation due to long-term disease remission, glucocorticoid sparing effect, and increase in the frequency of monocyclic disease course rather than a polycyclic or chronic articular pattern. Methods SD patients treated with canakinumab were grouped according to time between disease onset and canakinumab initiation (≤3 months vs. >3 months). Patients were enrolled from the international AutoInflammatory Disease Alliance (AIDA) Network registry for SD. Results Overall, 190 patients were enrolled, 35 (19%) treated with canakinumab within three months from SD onset and 155 (82%) starting canakinumab later. Glucocorticoids use decreased more rapidly in patients receiving canakinumab within 3 months from SD onset than among patients treated later, with reductions of 50% vs 6% at month 3 (p=0.0001), and 75% vs 32% at month 6 (p=0.004). In logistic regression analysis, canakinumab initiation within 3 months from disease onset was significantly associated with treatment discontinuation due to long-term remission (OR 4.83, 95% CI 1.08-23.19; p=0.04). A monocyclic course occurred in 49% of patients starting canakinumab ≤3 months versus 8% starting later (p<0.0001). Starting canakinumab within 3 months from disease onset was significantly associated with a monocyclic disease course compared with the chronic-articular (RRR 4.43, 95% CI 1.12-17.60; p=0.034) and polycyclic courses (RRR 8.97, 95% CI 1.29-62.3; p=0.03). Conclusions Early canakinumab initiation is associated with treatment discontinuation due to long-term remission and appears linked to a greater frequency of a monocyclic disease course.

OBJECTIVES:The progression of Behçet's disease (BD) from a mucocutaneous-limited form to major organ involvement (MOI) represents a significant challenge. This study aims to identify patients without MOI at BD onset who are at increased risk of developing MOI in later stages. METHODS:Patients' data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registry dedicated to BD. RESULTS:A total of 328 patients with exclusively mucocutaneous manifestations at BD onset were enrolled. Of these, 82 patients (25%) developed MOI over the entire follow-up period. Patients with minor oral aphthosis and no major oral aphthosis exhibited a reduced risk of developing MOI, with an odds ratio (OR) of 0.41 [95% confidence interval (95%CI): 0.22-0.79, P = 0.008]. Conversely, patients with both major and minor oral aphthosis had a significantly higher risk of developing MOI, with an OR of 12.76 (95%CI: 1.44-113, P = 0.02). Moreover, the development of MOI was associated with major oral aphthosis plus genital aphthosis (OR: 2.49, 95%CI: 1.1-5.6, P = 0.03), major oral aphthosis plus pseudofolliculitis (OR: 2.9, 95%CI: 1.15-7.4, P = 0.02) and major oral aphthosis plus both genital aphthosis and pseudofolliculitis (OR: 3.73, 95%CI: 1.22-11.4, P = 0.02). A positive family history for BD was associated with MOI (OR: 2.85, 95%CI: 1.08-7.58, P = 0.03). CONCLUSION:A positive family history and the presence of major oral aphthosis combined with minor oral aphthosis, genital aphthosis or pseudofolliculitis are associated with MOI development in patients with mucocutaneous BD at onset.

ObjectivesThis study aims to explore the application of machine learning techniques in assessing macrophage activation syndrome (MAS) in Still’s disease.MethodsA multicenter, observational, prospective study was conducted, including patients with Still’s disease enrolled in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) AOSD Study Group and the AutoInflammatory Disease Alliance (AIDA) Network Still’s Disease Registry.ResultsA total of 737 patients (age: 35.5 ± 17.8, male sex: 44.7%) with Still’s disease were assessed; 11.4% were affected by MAS, and 3% had a poor prognosis. First, random forest imputation was applied to the original dataset. Subsequently, a machine-learning-driven assessment was developed to explore MAS occurrence. Collectively, regression models, an exploration decision tree, and a random forest were applied, suggesting the importance of ferritin, age, C-reactive protein (CRP), and systemic score. A logistic regression model accounting for data leakage concerns was then generated using these variables, and missing values were imputed using random forest imputation. This analysis supported the role of the selected variables, which were further combined across different clinical scenarios to estimate the probability of MAS. The highest risk of MAS was estimated for patients simultaneously characterized by age ≥ 45 years, ferritin ≥ 4,178.10 ng/mL, CRP ≥ 27.15 mg/L, and a systemic score ≥ 7, corresponding to a 34.7% probability of MAS, as well as for those characterized by ferritin ≥ 4,178.10 ng/mL, CRP ≥ 27.15 mg/L, and systemic score ≥ 7, corresponding to a 33.5% probability of MAS.ConclusionsA machine-learning-driven prediction of MAS was explored in Still’s disease, highlighting the importance of age of onset, hyperferritinaemia, increased CRP, and multiorgan involvement. A combination of these features may suggest a clinician-friendly algorithm for stratifying the probability of MAS during Still’s disease.

Objective Olfactory dysfunction is a relatively frequent manifestation in systemic lupus erythematosus (SLE). The Italian Olfactory Identification Test (IOIT) may represent a suitable tool for detecting olfactory impairment in patients with SLE, due to its reliability and easiness of administration. This study aimed to evaluate the prevalence of smell impairment in patients with SLE and its correlation with clinical and serologic features. Methods Consecutive patients with SLE and healthy controls were enrolled. Clinical history, disease indices, and main laboratory parameters were collected. Olfactory function was assessed using the IOIT, testing 33 cards with different microencapsulated odorants. Results The cohort included 100 subjects: 50 patients with SLE (mean age ± SD: 51.3 ± 14.2; disease duration ± SD: 20.9 ± 13.2; female‐to‐male ratio: 5:1) and 50 age‐ and sex‐matched healthy controls. Hyposmia was observed in 30% of patients with SLE and 4% of healthy subjects. IOIT scores correlated significantly with cumulative organ damage measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (P = 0.017, r = 0.336). Hyposmia was associated with anti–β2‐glycoprotein I (anti‐β2GPI) antibodies (P = 0.029) and antidepressant therapy (P = 0.019). Cumulative damage was demonstrated to be an independent risk factor for hyposmia (odds ratio = 1.42, 95% confidence interval 1.02–1.98; P = 0.038). Conclusion The IOIT appears to be a suitable tool for evaluating olfactory dysfunction in SLE. The significant association between hyposmia and cumulative damage suggests that olfactory impairment may represent a clinical marker of long‐term organ damage. The association between hyposmia and the use of antidepressant therapy confirms the close relationship between the sense of smell and mood regulation. Furthermore, the association with anti‐β2GPI reinforces the link between olfactory dysfunction and chronic damage in SLE.