OBJECTIVES:Kawasaki disease (KD) is a systemic vasculitis that affects children under the age of five. Comprehensive data on KD patients with medium or large CAA are limited. This study aims to investigate the risk factors and long-term follow-up of KD patients with medium or large CAA in a Chinese cohort. METHODS:We performed a cohort study of 220 KD patients including 55 patients associated with medium or large CAA and 165 patients without coronary artery abnormality between January 2015 and April 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors. All enrolled patients were followed up for more than 12 months. RESULTS:Days to initial IVIG treatment, IVIG resistance, albumin level and platelet count were independent risk factors for KD patients with medium or large CAA based on multivariate logistic regression analysis. At a mean follow-up duration of 49 months, CAA subgroup analysis showed that 19 medium CAA cases (54.3%) promisingly regressed to normal coronary artery diameter, with the constituent ratios of small, medium, and large CAA being 31.4%, 8.6%, and 5.7%, respectively. In contrast, none of large CAA subgroup returned to normal coronary arteries. The constituent ratio of small, medium and large CAA was 15.0%, 25.0% and 60.0%. Besides, we found that coronary thrombosis occurred in 11 acute-phase cases (20.0%; 2 in the medium CAA, 9 in the large CAA), which increased to 18 cases (32.7%; 5 in the medium CAA, 13 in the large CAA) at the end of follow-up. CONCLUSIONS:Days to initial IVIG treatment, IVIG resistance, albumin levels and platelet count were risk factors for KD patients with medium or large CAA. The prognosis of medium or large CAA is not ideal during a long-term follow-up, particularly for large CAA.
OBJECTIVES:Population-based cohort studies show an association between systemic sclerosis (SSc) and lung cancer; however, a Mendelian randomisation analysis refutes causality. Herein, lung cancer risk is analysed in an academic inception SSc cohort, complemented by a meta-analysis of published data. METHODS:Patients evaluated within 12 months of SSc onset, between January 1995 and December 2020, with regular follow-up until December 2024, were included. Clinical manifestations, laboratory parameters, treatments and comorbidities were prospectively recorded. Age-standardised incidence ratio (SIR) of lung cancer was estimated using the Global Cancer Observatory database. Lung cancer determinants were evaluated with Cox proportional hazards models. A systematic literature search for the association between SSc and cancer and a meta-analysis of lung cancer SIRs from eligible studies was conducted. RESULTS:Among 180 patients (2,110 person-years follow-up), lung cancer was diagnosed in 12, after a mean 10.2±5.9 years from SSc onset. Age-SIR was 5.1 (95% CI 4.7-5.4) for the entire cohort, 3.8 (95% CI 3.5-4.1) for male and 9.5 (95% CI 8.7-10.3) for female patients. Diffuse subtype [HR = 4.22, 95% CI: 1.03-17.35] and smoking history [HR=4.49, 95% CI: 1.14-17.69] were associated with lung cancer development, whereas digital ulcers were inversely associated [HR: 0.13, 95% CI: 0.03-0.63]. The meta-analysis of 17 studies (27,563 SSc patients) yielded a pooled lung cancer age-SIR of 3.85 [95% CI (2.63-5.63)]. CONCLUSIONS:Long-term follow-up data from an SSc inception cohort indicate a fivefold increased lung cancer risk in SSc, nearly doubled among female patients. Further studies are warranted to inform screening strategies.
OBJECTIVES:This study aimed to explore the risk factors for progression in immunoglobulin G4-related disease (IgG4-RD) under watchful waiting and the temporal distribution of progression events to inform clinical decision-making. METHODS:A total of 40 IgG4-RD patients managed with the watchful waiting strategy were identified and included. Patients were categorised into 'without internal organ involvement' (WOI, n=26) and 'with internal organ involvement' (WI, n=14) groups. Baseline characteristics and progression rates were compared. Risk factors for progression were further identified using logistic and Cox regression analyses in the WOI group. The distribution of time to disease progression was summarised. RESULTS:Progression occurred in 12/40 patients (5 in WOI vs. 7 in WI). Kaplan-Meier analysis showed a significantly higher stability probability in the WOI group (p=0.048). Paranasal sinus involvement, high response index (RI), elevated eosinophil percentage (Eos%), and high IgE levels were significant risk factors for progression in WOI group. Notably, all progression events occurred within the first year of follow-up, with the estimated hazard function peaking at 6 to 8 months and declining thereafter. CONCLUSIONS:IgG4-RD patients with internal organ involvement exhibit a higher rate of disease progression under watchful waiting. Paranasal sinus involvement, high RI, high Eos%, and high IgE levels were identified as potential risk factors for disease progression. Intensive surveillance is especially warranted during the early phase.
Phospholipase D4 (PLD4) represents a highly specialised lysosomal 5´-to-3´ exonuclease functioning as a definitive molecular checkpoint governing innate immune homeostasis. Although structurally classified within the classical phospholipase D family, PLD4 is entirely devoid of lipid hydrolytic capacity, instead executing rigorous enzymatic degradation of sequestered single-stranded DNA and RNA. By strictly orchestrating the structural clearance of these localised nucleic acid ligands, this unique enzyme fundamentally restrains the aberrant hyperactivation of critical pattern recognition pathways, specifically Toll-like receptors 7 and 9. Consequently, genetic polymorphisms and profound transcriptional dysregulation of PLD4 actively drive a spectrum of severe systemic autoimmune pathologies, prominently encompassing systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis.This review systematically synthesises the precise molecular mechanisms dictating PLD4-mediated immunomodulation, elucidating its profound impact on cellular phenotypic plasticity and localised inflammatory cytokine cascades. Ultimately, we provide a rigorous translational framework contextualising PLD4 not merely as a fundamental biological regulator, but as a highly actionable therapeutic target for neutralising refractory inflammatory autoimmune diseases.
OBJECTIVES:Psychological distress influences pain and disease severity perception among patients affected by psoriatic arthritis (PsA). Alexithymia, a personal trait characterised by the difficulty in recognising and articulating emotions, has been observed in other rheumatic diseases, but its role in PsA remains underrecognised. We investigated the prevalence of alexithymia in PsA and its association with disease activity, psychological burden, and treatment complexity. METHODS:A cross-sectional observational study was conducted across three Italian rheumatology centers, enrolling PsA patients on stable biological therapy. Toronto Alexithymia Scale (TAS-20), Pain Catastrophising Scale (PCS), Beck's Depression Inventory (BDI), Widespread Pain Index (WPI), Symptom Severity Scale (SSS), alongside Disease Activity Index for PsA (DAPSA), Bath Axial Spondyloarthritis Disease Activity Index (BASDAI), and Axial Spondyloarthritis Disease Activity Index-C Reactive Protein (ASDAS-CRP) were assessed at last follow-up. Associations with alexithymia were explored by univariate analyses, Spearman correlation, and multivariable logistic regression. RESULTS:Among 207 PsA patients, 63 (30.4%) were classified as alexithymic (TAS≥61). Patients with alexithymia exhibited significantly higher pain-VAS, patient and physician global assessment, tender joint count, PCS, WPI+SSS, and BDI scores, as well as elevated DAPSA, BASDAI, ASDAS-CRP, while inflammatory markers and swollen joint count were similar between groups. Alexithymic patients underwent multiple biological therapy lines and reported increased conventional synthetic DMARDs and non-steroidal anti-inflammatory drug usage. A strong correlation emerged between TAS-20 and PCS, alongside female sex, concomitant fibromyalgia and higher DAPSA were independent predictors of alexithymia in multivariable model. CONCLUSIONS:Alexithymia is present in PsA and is linked to increased pain perception, disease activity and treatment burden.
OBJECTIVES:To synthesise current evidence on artificial intelligence (AI) in rheumatology with a specific focus on AI-induced technostress, job insecurity and professional identity, and to propose a pragmatic framework for an 'AI-augmented' rheumatologist. METHODS:A narrative review was conducted using focused searches for articles published between January 2015 and March 2026. Search terms combined AI- and rheumatology-related concepts with terms related to technostress, burnout and professional identity. Reference lists of key rheumatology AI reviews and empirical studies were screened for additional publications. Eligible works included empirical studies, reviews and conceptual papers on AI in rheumatology or AI-related technostress and psychological or professional consequences for physicians. RESULTS:Current AI applications in rheumatology span imaging, risk prediction, data integration and large language model (LLM)-based tools, but routine use remains low despite largely positive expectations among rheumatologists and patients. Evidence from mixed-specialty cohorts indicates that AI-related self-esteem threat is a central driver of job insecurity and may contribute to burnout. Rheumatology's reliance on longitudinal pattern recognition, uncertainty management and relationship-centred care makes perceived threats to expertise particularly salient, although similar dynamics likely affect other specialties. Building on this evidence, a four-pillar framework for an 'AI-augmented' rheumatologist is proposed: clear role boundaries between humans and AI, rheumatology-specific AI literacy, clinician- and teamled implementation and governance, and routine monitoring of technostress and well-being. CONCLUSIONS:AI can meaningfully support rheumatology care and, when well-designed and implemented, may even reduce certain forms of technostress by offloading administrative and repetitive tasks. At the same time, AI-related technostress, perceived self-esteem threat and job insecurity can undermine professional identity and wellbeing if introduced without attention to role boundaries, governance and multiprofessional collaboration. The proposed framework aims to help rheumatologists and institutions integrate AI in ways that preserve core professional values and clinician well-being.
OBJECTIVES:Anti-topoisomerase I antibody (ATA) is typically associated with diffuse cutaneous systemic sclerosis (dcSSc). However, subset of limited cutaneous SSc (lcSSc) patients also present with ATA positivity. Emerging data suggest that ATA-positive lcSSc may represent a distinct or intermediate clinical phenotype. This study aimed to compare the demographic, clinical, and treatment features of early ATA-positive lcSSc patients with those of ACA-positive lcSSc and ATA-positive dcSSc patients. METHODS:Patients were recruited from the multicentre Turkish SOLAR cohort (Systemic sclerOsis Longitudinal Assessment Registry). Among 295 SSc patients screened, 172 were included: 74 ACA-positive lcSSc, 55 ATA-positive lcSSc, and 43 ATA-positive dcSSc. Demographic, clinical, and treatment-related variables were analysed and compared across groups. RESULTS:ATA-positive lcSSc patients were younger at the onset of Raynaud's phenomenon (RP) (p=0.042), the first non-RP symptom (p=0.016), and at diagnosis (p=0.018) compared with ACA-positive lcSSc patients. Interstitial lung disease (ILD) was significantly more frequent in ATA-positive lcSSc (74.5%) than ACA-positive lcSSc (8.1%, p<0.001) and was comparable to ATA-positive dcSSc. Modified Rodnan skin scores were highest in ATA-positive dcSSc but were also significantly elevated in ATA-positive lcSSc (p<0.001). Pitting scars were more frequent in dcSSc. Among patients with ILD, ATA-positive lcSSc and ATA-positive dcSSc showed similar HRCT patterns. ATA-positive lcSSc patients were more frequently treated with glucocorticoids and mycophenolate mofetil than ACA-positive lcSSc, whereas cyclophosphamide was highest in dcSSc. CONCLUSIONS:ATA-positive lcSSc patients exhibit a clinically distinct phenotype characterized by a substantial risk of internal organ involvement, despite having less extensive skin disease. Their overlap with dcSSc and divergence from ACA-positive lcSSc highlight the importance of incorporating both skin involvement and serologic subtyping into the early management and risk stratification of SSc.
Idiopathic and recurrent pericarditis are increasingly recognised as autoinflammatory conditions driven by the NLRP3 inflammasome and interleukin-1 signalling. Despite this shift in understanding, the misuse of high-dose corticosteroids has often led to a 'massacre of the innocents', transforming acute events into chronic, steroid-dependent diseases. This narrative review analyses the evolution of corticosteroid use in pericarditis, emphasising the transition from aggressive loading doses to the low-dose, 'rheumatological' strategies codified in the 2025 European Society of Cardiology (ESC) guidelines.Evidence confirms that medium-dose prednisone (0.2-0.5 mg/kg/day), when integrated into triple therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine, reduces recurrence rates and iatrogenic toxicity compared to traditional high-dose regimens (1.0 mg/kg/day). A critical challenge remains the tapering process; rapid withdrawal triggers inflammatory rebounds, necessitating meticulous, long-lasting (months-years), C-reactive protein (CRP)-guided reductions as small as 5 to 1.25 mg every two to six weeks, similar to the tapering used in polymyalgia rheumatica. Chronic maintenance with low-dose prednisone (≤5 mg/day) may be considered in selected cases, with a good risk-benefit balance. The elderly usually require medium dosages (e.g. prednisone 12.5-25 mg), pregnant women no more than 10 mg, while children should avoid chronic corticosteroid therapy. CRP-negative cases may benefit from low doses (5 mg). Given the long-term duration of therapy, bone protection therapy is essential yet underutilised, while protonpump inhibitors should be used only for concomitant NSAIDs therapy. Corticosteroids are generally ineffective in chronic idiopathic pericardial effusions with normal CRP.In conclusion, modern management redefines corticosteroids as a precision tool rather than a blunt anti-inflammatory agent.
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.
