Clinical Rheumatology[JOURNAL]
Sun
200 papers
Serum DNASE1L3 level as a potential exploratory biomarker for Behçet's disease: a preliminary study.
Naderi Far P, Ozturk N, Alkan Melikoglu M … +2 more , Sarıkaya F, Dashan M
Clin Rheumatol · 2026 Jul · PMID 42400811 · Publisher ↗
OBJECTIVE: Behçet's disease is a chronic, inflammatory vasculitis affecting multiple systems. In addition to existing laboratory parameters used for the diagnosis and monitoring of Behçet's disease, new biomarkers are ne...
OBJECTIVE: Behçet's disease is a chronic, inflammatory vasculitis affecting multiple systems. In addition to existing laboratory parameters used for the diagnosis and monitoring of Behçet's disease, new biomarkers are needed to improve diagnostic accuracy. The levels and activity of DNASE1L3, an enzyme that degrades chromatin released into circulation during apoptotic processes and can initiate autoimmune mechanisms, have been associated with autoimmune diseases. This study was designed to determine the levels of DNASE1L3 in patients with Behçet's disease, assess its relationship with clinical and inflammatory parameters, and evaluate its potential as a diagnostic biomarker. METHODS: This study included 45 patients diagnosed with Behçet's disease and 45 age and sex-matched healthy controls. Serum DNASE1L3 levels were measured in both groups using the enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum DNASE1L3 levels were significantly lower in patients with Behçet's disease (7.14 ± 1.81 ng/mL) compared to the healthy control group (15.79 ± 3.14 ng/mL) (p < 0.001). A statistically significant negative correlation was observed between serum DNASE1L3 levels and both CRP (r = - 0.684, p < 0.001) and ESR (r = - 0.524, p < 0.001). According to ROC curve analysis, a serum DNASE1L3 cutoff value of 9.53 ng/mL distinguished patients with Behçet's disease from healthy individuals with 96% sensitivity and 93% specificity. For this threshold, the positive predictive value was 95% and the negative predictive value was 93% (AUC = 0.983; p < 0.001; positive likelihood ratio, 21.13; negative likelihood ratio, 0.07). CONCLUSION: The findings of this preliminary study suggest that serum DNASE1L3 may represent a promising candidate biomarker for Behçet's disease. However, further validation in larger, independent cohorts is required before its potential clinical utility can be established. Key Points • Serum DNASE1L3 levels are significantly lower in patients with Behçet's disease compared to healthy individuals. • DNASE1L3 levels show a strong negative correlation with acute phase reactants, including CRP and ESR. • Low DNASE1L3 levels may reflect impaired extracellular DNA clearance and contribute to the inflammatory process in Behçet's disease. • Serum DNASE1L3 levels show potential as an exploratory biomarker for the clinical evaluation of Behçet's disease, providing a basis for further validation in larger clinical cohorts.
Serum ferritin as a predictor of major adverse cardiovascular events in Takayasu arteritis: a two-center retrospective cohort study.
Ci W, Kong F, Du J … +3 more , Zhang Y, Zhao Y, Pan L
Clin Rheumatol · 2026 Jul · PMID 42399575 · Publisher ↗
OBJECTIVES: Elevated serum ferritin levels predict adverse outcomes in many autoimmune diseases. However, its clinical significance in Takayasu arteritis (TAK) is not clear. This study aimed to evaluate the predictive va...
OBJECTIVES: Elevated serum ferritin levels predict adverse outcomes in many autoimmune diseases. However, its clinical significance in Takayasu arteritis (TAK) is not clear. This study aimed to evaluate the predictive value of serum ferritin for major adverse cardiovascular events (MACEs) in TAK. METHOD: A two-center retrospective cohort study was conducted. A total of 189 treatment-naïve TAK patients who underwent serum ferritin testing at baseline were consecutively enrolled and followed longitudinally. The association between serum ferritin levels and adverse events was assessed using survival analyses. RESULTS: Thirty-seven patients (19.6%) experienced MACEs during a median follow-up of 34.00 (20.00-55.00) months. Using the cut-off value of 68.6 μg/L, patients with high serum ferritin levels exhibited significantly higher MACE rates at 12, 36, 60, and 96 months compared to those with low levels (χ2 = 8.59, P = 0.003; χ2 = 15.23, P < 0.001; χ2 = 11.48, P < 0.001; χ2 = 12.63, P < 0.001, respectively). Serum ferritin was an independent predictor of MACEs in TAK at 96 months, both when analyzed as a continuous variable (HR: 1.003, 95% CI: 1.001-1.006, P = 0.007) and as a categorical variable (HR: 2.609, 95% CI: 1.280-5.320, P = 0.008). Furthermore, the predictive value of serum ferritin remained consistent across most subgroups, except among male patients (P for interaction = 0.018, P > 0.05), smokers (P for interaction = 0.027, P > 0.05) and patients receiving glucocorticoids (P for interaction = 0.033, P > 0.05). CONCLUSIONS: Elevated serum ferritin is an independent predictor of MACEs in TAK. Patients with increased baseline serum ferritin levels should undergo close monitoring and may benefit from intensified therapeutic interventions due to their higher risk of adverse events. Key Points • Elevated Serum ferritin is associated with poorer prognosis in Takayasu arteritis. • Serum ferritin is an independent prognostic biomarker in Takayasu arteritis. • The predictive value of serum ferritin is consistent across most subgroups.
Inverse association between metabolic dysfunction-associated steatotic liver disease and incident rheumatoid arthritis in middle-aged adults with chronic hepatitis B.
Park J, Kang ES, Jeong S
Clin Rheumatol · 2026 Jul · PMID 42399574 · Publisher ↗
INTRODUCTION: Chronic hepatitis B (CHB) frequently coexists with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to determine whether MASLD is a risk factor for incident rheumatoid arth...
INTRODUCTION: Chronic hepatitis B (CHB) frequently coexists with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to determine whether MASLD is a risk factor for incident rheumatoid arthritis among middle-aged patients with CHB in a real-world setting. METHOD: A population-based cohort study was conducted using the Korean National Health Insurance Service, including 114,425 middle-aged CHB individuals (aged 40-65 years) classified as having either MASLD or non-SLD. Cox proportional hazards regression and Fine-Gray subdistribution hazard models were applied to assess RA risk, accounting for all-cause mortality as a competing event. All patients were followed up until RA, death, or January 31, 2022. RESULTS: During 792,777 person-years of follow-up, 867 incident RA cases were identified. CHB patients with MASLD had a significantly lower risk of RA development compared to non-SLD participants (subdistribution hazard ratio [SHR], 0.82; 95% CI, 0.69-0.97). This effect was more obvious among younger aged patients (< 50 years). Additionally, higher daily alcohol consumption (1 g/day) was associated with an increased adjusted SHR for RA among all middle-aged CHB patients (1.007; 95% CI, 1.003-1.012). CONCLUSIONS: In middle-aged patients with CHB, the presence of MASLD was associated with a lower risk of developing RA. However, the underlying mechanisms remain unclear, and residual confounding by CHB severity, liver disease stage, or antiviral treatment may have contributed to the observed association. Further studies are warranted to clarify these potential mechanisms linking CHB, MASLD, and RA risk. Key Points • In a nationwide Korean cohort of 114,425 middle-aged adults with CHB, MASLD was associated with a lower incidence of seropositive rheumatoid arthritis compared with non-steatotic liver disease. • In patients with CHB, MASLD may represent a distinct clinical state whose meaning could differ from standalone MASLD because it may be intertwined with the CHB disease stage and immune milieu.
Extension of cytokines' role in Behcet's disease associated peripheral neuropathy.
Elsonbaty A, Hetta H, Nasreldein A … +1 more , Hassanien M
Clin Rheumatol · 2026 Jul · PMID 42397645 · Publisher ↗
BACKGROUND/OBJECTIVE: Behçet's disease (BD) is a chronic multisystem inflammatory disorder with diverse neurological manifestations. While central nervous system involvement is well recognized, peripheral neuropathy rema...
BACKGROUND/OBJECTIVE: Behçet's disease (BD) is a chronic multisystem inflammatory disorder with diverse neurological manifestations. While central nervous system involvement is well recognized, peripheral neuropathy remains an underdiagnosed and poorly understood complication. Chemokines, particularly C-C motif chemokine ligand 21 (CCL21), play a critical role in immune-mediated neuroinflammation and have been implicated in several autoimmune diseases. This study aimed to investigate the association between selected CCL21 gene polymorphisms and BD-associated peripheral neuropathy, and to assess their relationship with disease activity. METHODS: This cross-sectional observational study included 42 adult patients with BD and 20 age- and sex-matched healthy controls. All patients underwent comprehensive clinical and neurological evaluation, assessment of disease activity, and nerve conduction studies. Genotyping of CCL21 single nucleotide polymorphisms rs951005, rs2492358, and rs2812378 were performed for patients and controls. RESULTS: Electrophysiological evidence of peripheral neuropathy was detected in all evaluated Behçet's disease patients, despite only 50% reporting clinical neuropathic symptoms. Polyneuropathy was the predominant pattern, with sensory and mixed nerves more frequently affected than purely motor nerves, and greater involvement of upper limb nerves. A significant difference in the distribution of the CCL21 rs2492358 polymorphism was observed between patients and controls (p = 0.001). Additionally, the rs951005 polymorphism was significantly associated with higher disease activity scores (p = 0.009). CONCLUSION: Peripheral neuropathy is a frequent and often subclinical manifestation of BD. CCL21 gene polymorphisms appear to contribute to both peripheral neuropathy association and disease activity, highlighting CCL21 as a potential biomarker linking systemic inflammation to peripheral nerve involvement. Key Points • Chemokine dysregulation previously found to play a central role in the development of neuroinflammation. • This cross-sectional study identifies specific chemokines' gene of CCL21 linked to peripheral neuropathy in Behcet's disease. • Results may guide future therapeutic strategies targeting chemokine modulation.
Renal osteodystrophy with near-complete bilateral sacroiliac ankylosis: a bat-like pelvic configuration on CT.
Onder RO, Aslan S
Clin Rheumatol · 2026 Jul · PMID 42397644 · Publisher ↗
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Serum exosomal tRNA-derived small RNAs as diagnostic biomarkers for primary Sjögren's syndrome: a combined model with autoantibodies.
Dong N, Xie S, Chen F … +5 more , Khan A, Liu W, Shi B, Li Z, Yang P
Clin Rheumatol · 2026 Jul · PMID 42397643 · Publisher ↗
OBJECTIVE: The identification of reliable biomarkers for the early diagnosis and monitoring of primary Sjögren's syndrome (pSS) remains a critical clinical need. Extracellular vesicles (EVs), which carry diverse molecula...
OBJECTIVE: The identification of reliable biomarkers for the early diagnosis and monitoring of primary Sjögren's syndrome (pSS) remains a critical clinical need. Extracellular vesicles (EVs), which carry diverse molecular cargo, including tRNA-derived small RNAs (tsRNAs), have emerged as novel regulators of immune responses. This study aimed to profile EV-associated tsRNAs in pSS and evaluate their diagnostic potential. METHODS: Serum EVs were isolated from pooled samples (20 individuals per pool) of pSS patients and age- and sex-matched healthy controls (HCs). High-throughput tsRNA sequencing was performed to identify differentially expressed candidates. In the training cohort (23 pSS and 23 HCs), candidate tsRNAs were quantified in serum EVs using SYBR Green-based RT-qPCR. The top two tsRNAs were validated in an independent cohort of 92 individuals (46 pSS and 46 HCs). The diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Bioinformatic analyses were conducted to explore the potential functional pathways associated with the identified tsRNAs. RESULTS: Among the differentially expressed tsRNAs, serum exosomal levels of tRNA-Val-CAC_5_end and tRNA-His-GTG_5_end were significantly elevated in pSS patients compared to HCs. ROC analysis revealed that tRNA-Val-CAC_5_end had an AUC of 0.9750 (95% CI, 0.9496-1.000), while tRNA-His-GTG_5_end demonstrated a higher AUC of 0.9759 (95% CI, 0.9513-1.000). When compared to conventional pSS markers, anti-SSA and anti-SSB antibodies showed AUCs of 0.9966 (95% CI, 0.9893-1.000) and 0.9725 (95% CI, 0.9444-1.000), respectively. Integrating tsRNAs with autoantibodies enhanced diagnostic accuracy, with the combination of both candidate tsRNAs with anti-SSA achieving the highest AUC of 0.9971 (95% CI, 0.9907-1.000). Bioinformatic analyses further suggested that these tsRNAs may be involved in immune regulation by modulating key signaling pathways, providing mechanistic insights into their clinical relevance. CONCLUSION: This study identifies EV-derived tsRNAs as promising non-invasive biomarkers for the early diagnosis and monitoring of pSS. These findings offer new perspectives on EV-mediated tsRNA regulation in autoimmune diseases and highlight their translational potential for clinical applications. Key Points • Two serum exosomal tsRNAs (tRNA-Val-CAC_5_end, tRNA-His-GTG_5_end) are upregulated in pSS; combined with anti-SSA, they form a diagnostic model with AUC 0.9971. • This tsRNA panel performed well in anti-SSA/SSB seronegative pSS, with its combination reaching an AUC of 0.9881. • Expression changes of the two tsRNAs are independent of inflammation and immunosuppressive therapy; they are hypothesized to be involved in pSS-related neuro-immune pathogenic mechanisms.
Risk of Femoral Head Osteonecrosis Following Hip Trauma in Adults With Systemic Lupus Erythematosus.
Youssef A, Shi Q, Lee JA … +1 more , Zai AH
J Clin Rheumatol · 2026 Jun · PMID 42391522 · Publisher ↗
BACKGROUND/OBJECTIVE: Systemic lupus erythematosus (SLE) is a known risk factor for femoral head osteonecrosis (FHON), but its impact on FHON risk following hip trauma has not been well characterized. We evaluated whethe...
BACKGROUND/OBJECTIVE: Systemic lupus erythematosus (SLE) is a known risk factor for femoral head osteonecrosis (FHON), but its impact on FHON risk following hip trauma has not been well characterized. We evaluated whether adults with SLE have an increased risk of FHON after hip trauma compared with patients without SLE. METHODS: We conducted a retrospective cohort study using de-identified electronic health record data from the TriNetX Research Network. Adults aged 18 to 65 years with an incident hip trauma diagnosis and no prior FHON were included. SLE was defined by the presence of an ICD-10 diagnosis code for SLE documented in the electronic health record. Patients with and without SLE were matched 1:1 using propensity scores incorporating demographics, baseline comorbidities, and systemic glucocorticoid exposure. The primary outcome was incident FHON within 5 years following hip trauma, with a secondary analysis evaluating FHON risk in matched cohorts without hip trauma. Kaplan-Meier and Cox proportional hazards analyses were performed. RESULTS: Among adults with incident hip trauma, patients with SLE had a higher 5-year incidence of FHON than patients without SLE. In propensity score-matched time-to-event analyses, SLE was associated with an increased hazard of osteonecrosis (hazard ratio: 2.9; 95% CI: 2.0-4.3; log-rank p < 0.001). These findings were consistent with a similarly elevated baseline risk of FHON observed in patients with SLE in analyses without hip trauma. CONCLUSIONS: SLE is associated with an increased FHON risk both with and without hip trauma. The modest absolute post-trauma risk difference supports symptom-guided vigilance rather than routine imaging after trauma. PRACTICAL POINT: Persistent, progressive, or atypical hip symptoms after trauma in patients with SLE warrant clinical vigilance for osteonecrosis, but these findings do not support routine imaging of all patients with SLE after trauma.
Efficacy and Safety of Intravenous Golimumab in Patients With Ankylosing Spondylitis and Complete Spinal Ankylosis: Results Through Week 52 of the GO-ALIVE Study: Erratum.
J Clin Rheumatol · 2026 Jun · PMID 42391506 · Publisher ↗
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Efficacy and Safety of Intravenous Golimumab in Ankylosing Spondylitis Patients With Early and Late Disease Through One Year of the GO-ALIVE Study: Erratum.
J Clin Rheumatol · 2026 Jun · PMID 42391502 · Publisher ↗
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Microbiome Dysbiosis as a Potential Driver of Inflammatory Mimicry in Pachydermoperiostosis-associated Hypertrophic Osteoarthropathy.
Ghani MZ, Kotak P, Raza A … +1 more , Htun SH
J Clin Rheumatol · 2026 Jun · PMID 42391478 · Publisher ↗
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Monosodium urate crystals induce lytic macrophage death partially dependent on both pyroptosis and necroptosis.
Geng Z, Wu D, Hou Y … +9 more , Kang L, Zhang X, Feng Z, Song J, Chen D, Zhang T, Xu L, Gao X, Lin Z
Clin Rheumatol · 2026 Jul · PMID 42390698 · Publisher ↗
OBJECTIVES: Macrophage lytic death induced by monosodium urate (MSU) crystals is critical for gout initiation, but its mechanisms remain unclear. MSU activates the NOD-like receptor family pyrin domain-containing protein...
OBJECTIVES: Macrophage lytic death induced by monosodium urate (MSU) crystals is critical for gout initiation, but its mechanisms remain unclear. MSU activates the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome and canonical pyroptosis; this study aimed to define the cell death pathways mediating MSU crystal-induced macrophage death. METHOD: We assessed canonical inflammasome activation (apoptosis-associated speck-like protein containing a CARD (ASC) speck, caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β)) in macrophages. Using genetically deficient macrophages (GSDMD⁻/⁻, NLRP3⁻/⁻, and caspase-1⁻/⁻) and pharmacological inhibitors, we evaluated lytic death and in vivo inflammation. We also checked caspase-3/gasdermin E (GSDME) pyroptosis, necroptosis, ferroptosis, and ROS. RESULTS: MSU crystals strongly activated canonical inflammasome signaling, as evidenced by ASC speck formation, caspase-1 activation, GSDMD cleavage, and IL-1β secretion. However, genetic ablation of GSDMD, NLRP3, or caspase-1 did not prevent MSU crystal-induced macrophage lytic death. Similarly, deficiency of GSDMD or NLRP3 did not alleviate inflammation in mouse models of gout. MSU crystals did not trigger caspase-3/GSDME-dependent pyroptosis. While necroptosis contributed to cell death when canonical pyroptosis was blocked, inhibiting necroptosis alone was insufficient to abolish MSU crystal-induced lysis. Combined inhibition of caspases and necroptosis moderately, but significantly, reduced lytic death, whereas additional blockade of ferroptosis or reactive oxygen species (ROS) did not further enhance this protective effect. CONCLUSIONS: MSU crystal-induced macrophage lytic death represent a complex cell death program that is not exclusively dependent on canonical pyroptosis or necroptosis. These findings uncover a previously unrecognized mechanism of MSU-mediated cytotoxicity and offer novel insights into the molecular pathogenesis of gout. Key Points • Monosodium urate (MSU) crystals trigger macrophage lytic cell death via synergistic canonical pyroptosis and necroptosis, instead of a single cell death pathway. GSDME-dependent pyroptosis, ferroptosis, and ROS are not pivotal drivers of this process. • Combined inhibition of canonical pyroptosis and necroptosis partially reduces MSU crystal-induced macrophage death.
A kaleidoscopic autoimmune syndrome (COVAS) following COVID-19 exposure.
Li Y, Xu C, Li Z
Clin Rheumatol · 2026 Jul · PMID 42390697 · Publisher ↗
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The young adult with Juvenile Idiopathic Arthritis (JIA): A clinical review of transition, complications, and psychosocial management.
Rozenblyum EV, Gakhal NK
Best Pract Res Clin Rheumatol · 2026 Jun · PMID 42379955 · Publisher ↗
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, and up to half of patients continue to experience active disease or complications into adulthood. Despite this, adult rheumat...
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, and up to half of patients continue to experience active disease or complications into adulthood. Despite this, adult rheumatology care remains largely oriented toward adult-onset disease, creating a mismatch in expertise for patients with childhood-onset arthritis. As a result, adult providers must address clinical challenges unique to childhood-onset disease, including persistent inflammation, temporomandibular joint (TMJ) involvement, long-term medication exposure, chronic pain, psychosocial morbidity, and extra-articular manifestations such as uveitis. Transition gaps are common and contribute to medication discontinuation, loss to follow-up, and disease flare. This review summarizes the long-term outcomes of JIA relevant to adult rheumatologists and outlines best practices in screening and management across key domains, including uveitis, TMJ arthritis, mental health, and educational and vocational participation. The review also highlights evidence-based practical strategies for building transition-informed adult rheumatology practices.
Risk of arrhythmia following ankylosing spondylitis, 2012-2023: a nationwide cohort study.
Lee SW, Song C, Kim M … +2 more , Jung H, Bae Y
Clin Rheumatol · 2026 Jun · PMID 42377684 · Publisher ↗
OBJECTIVES: Ankylosing spondylitis (AS) may increase arrhythmia risk through systemic inflammation, cardiac remodeling, and conduction abnormalities, but population-level evidence is limited. We evaluated this risk using...
OBJECTIVES: Ankylosing spondylitis (AS) may increase arrhythmia risk through systemic inflammation, cardiac remodeling, and conduction abnormalities, but population-level evidence is limited. We evaluated this risk using a nationwide matched cohort in South Korea. METHODS: We used the Korean National Health Insurance Service cohort (2012-2023) in a retrospective matched study. AS was defined as ICD-10 M45 with copayment registration, and incident arrhythmia was defined as the first recorded diagnosis with ICD-10 codes I47-I49. Each AS case was matched to 10 controls by sex and screening year using a propensity score. We estimated incidence rates, incidence rate ratios, and hazard ratios with Cox models. RESULTS: We analyzed 3,022 patients with AS and 30,220 controls (mean follow-up 4.3 years). Arrhythmia occurred in 129 patients (4.3%) and 927 controls (3.1%). The crude incidence rate (IR) per 1,000 person-years was 9.90 in AS vs 7.05 in controls, yielding an incidence rate ratio (IRR) of 1.41 (95% CI 1.17-1.69). Risk was highest in women < 60 years (IRR 1.95, 95% CI 1.33-2.87). CONCLUSIONS: AS was associated with elevated arrhythmia risk, particularly in younger women. These findings support structured rhythm-risk awareness in AS care, while interval-specific adjusted analyses remained exploratory. Key Points • Patients with ankylosing spondylitis have a significantly increased risk of arrhythmia compared with matched controls. • The excess risk is most pronounced in younger women, highlighting a vulnerable subgroup. • These findings support structured rhythm-risk awareness and individualized cardiovascular monitoring in ankylosing spondylitis care, with the recognition that interval-specific adjusted estimates remained exploratory.
Polyarteritis nodosa and antiphospholipid syndrome: a systematic review of a rare and challenging overlap between vasculitis and thrombotic vasculopathy.
de Carvalho JF, de Araujo RPC
Clin Rheumatol · 2026 Jun · PMID 42377683 · Publisher ↗
BACKGROUND: The coexistence of polyarteritis nodosa (PAN) and antiphospholipid syndrome (APS) is rarely reported and remains poorly characterized. Both conditions may involve vascular injury, but through distinct mechani...
BACKGROUND: The coexistence of polyarteritis nodosa (PAN) and antiphospholipid syndrome (APS) is rarely reported and remains poorly characterized. Both conditions may involve vascular injury, but through distinct mechanisms-necrotizing inflammation in PAN and thrombotic vasculopathy in APS. Their overlap may result in a unique and potentially severe clinical phenotype, posing diagnostic and therapeutic challenges. In addition, differentiating inflammatory vasculitic injury from thrombotic vascular occlusion may be particularly difficult in this overlap setting, especially in patients with catastrophic presentations. OBJECTIVE: To systematically review all published cases describing the association between PAN and APS, focusing on clinical features, laboratory findings, pathophysiological insights, management strategies, and outcomes. METHODS: A systematic search was conducted in PubMed/MEDLINE, Scopus, and Web of Science from inception through 2026. The search included terms related to "polyarteritis nodosa" and "antiphospholipid syndrome." Only studies reporting cases fulfilling accepted diagnostic or classification criteria for PAN and APS were included. Data extraction encompassed demographic characteristics, temporal relationship between diseases, clinical manifestations, antiphospholipid antibody profiles, imaging and histopathological findings, treatments, and outcomes. Due to heterogeneity and limited sample size, a descriptive analysis was performed. Because of the rarity of this overlap syndrome, the available evidence consisted predominantly of case reports and small case series, which were critically analyzed within a systematic review framework. RESULTS: A small number of cases were identified, all reported as case reports or small case series. Most patients were middle-aged males, although one pediatric case was described. The temporal relationship varied, with simultaneous diagnosis being most common, while in some cases APS developed after PAN onset. Clinically, patients exhibited features of systemic PAN, including visceral involvement, neuropathy, and hypertension, alongside thrombotic events characteristic of APS, such as arterial occlusions, renal infarctions, stroke, and limb ischemia. Antiphospholipid antibodies-particularly anticardiolipin antibodies and lupus anticoagulant-were frequently detected. A distinctive feature was the coexistence of aneurysmal lesions and thrombosis. Treatment generally included corticosteroids and cyclophosphamide, often combined with anticoagulation. Outcomes were heterogeneous, ranging from clinical improvement to severe complications, including amputations and death. Several reports also raised the possibility of catastrophic antiphospholipid syndrome (CAPS), further complicating the distinction between inflammatory multiorgan vasculitis and thrombotic microangiopathic disease. CONCLUSIONS: The association between PAN and APS represents a rare but clinically significant overlap syndrome characterized by the interplay between inflammatory vasculitis and thrombotic mechanisms. Recognition of this entity is essential, as it has important implications for diagnosis and management. Emerging evidence suggests that endothelial dysfunction, complement activation, NETosis, and thromboinflammatory pathways may contribute to the pathogenesis of this overlap phenotype. Future studies are needed to better define its pathogenesis, optimize therapeutic strategies, and improve outcomes.
Association of metformin with osteoarthritis progression and total joint arthroplasty: evidence from the UK Biobank, a large population-based cohort study.
Kang Y, Liu Y, Long L … +12 more , Chen W, Zhang Z, Gu M, Wang C, Li C, Zhang S, Pan B, Wu X, Mobasheri A, Zhang Z, Sheng P, Zheng L
Clin Rheumatol · 2026 Jun · PMID 42371366 · Publisher ↗
OBJECTIVE: To assess the association between metformin and osteoarthritis (OA) development and total joint arthroplasty (TJA) in a large prospective cohort. METHODS: From the UK Biobank, 348,070 people between the ages o...
OBJECTIVE: To assess the association between metformin and osteoarthritis (OA) development and total joint arthroplasty (TJA) in a large prospective cohort. METHODS: From the UK Biobank, 348,070 people between the ages of 40 and 69 who did not have OA or TJA at baseline were included between 2006 and 2010 and investigated until January 2021. We used multivariable-adjusted Cox regression to test for an association between metformin and OA diagnosis (n = 51,111) and OA-related TJA (n = 21,754) in the cohort. Models 1 and 2 were adjusted for age, sex, and diabetes. Model 2 was also adjusted for additional variables, including the Townsend Deprivation Index, ethnicity, household income, body mass index, glycated hemoglobin, smoking and alcohol status, physical activity, hypertension, and medications including antihypertensive drug use, statin use, insulin treatment, aspirin use and glucosamine/chondroitin supplementation. RESULTS: At baseline, 14,128 (4.06%) of the 348,070 participants reported metformin prescriptions. The hazard ratio (HR) for OA, including knee OA (HR, 0.74; 95% confidence intervals (CI), 0.69 to 0.80) and hip OA (HR, 0.74; 95% CI 0.67 to 0.82), was 0.74 (95% CI, 0.70 to 0.77) for metformin users versus nonusers, but not hand OA (HR, 0.91; 95% CI 0.68 to 1.21). Metformin also reduced the risk of TJA (HR, 0.72; 95% CI 0.67 to 0.78). For OA, the association seemed to be stronger among nonobese, nondiabetic, and nonhypertensive participants (all p < 0.05). CONCLUSIONS: Metformin seems to reduce the risk of OA and TJA and may protect against OA in the general population.
Six-session non-operative exercise program yields sustained benefits for up to 18 months in end-stage knee osteoarthritis: a retrospective cohort study.
Lee WY, Li LMK, Chen NCY … +6 more , Leung CSM, Tsui AYC, Zhang X, Cao M, Yung PS, Ong MT
Clin Rheumatol · 2026 Jun · PMID 42371365 · Publisher ↗
INTRODUCTION/OBJECTIVES: Prolonged waiting times for total knee replacement (TKR) leave patients with end-stage knee osteoarthritis (OA) with persistent pain and functional limitation. We evaluated the effectiveness of a...
INTRODUCTION/OBJECTIVES: Prolonged waiting times for total knee replacement (TKR) leave patients with end-stage knee osteoarthritis (OA) with persistent pain and functional limitation. We evaluated the effectiveness of a structured physiotherapy-led non-operative program for patients awaiting TKR. METHOD: This retrospective cohort included 2,243 end-stage knee OA patients awaiting TKR (October 2021-March 2024). The Structured Non-Operative Treatment Program (SNTP) comprised six sessions delivered over one year, integrating aerobic, strengthening, neuromuscular exercises, and education to support lifestyle modification and home exercise adherence. Outcomes were assessed at baseline, program completion, and longitudinally thereafter; analyses focused on follow-up up to 2 years due to attrition. Primary outcomes were pain (Numeric Pain Rating Scale, NPRS), perceived change (Numeric Global Rating of Change, NGRCS), and knee function (Knee Injury and Osteoarthritis Outcome Score, KOOS). RESULTS: Participants were stratified by baseline Knee Society Score (KSS): Poor (≤ 66), Fair (67-76), Good (77-89), and Excellent (90-100). Significant improvements were observed across most outcomes in all subgroups. Total KSS and KSS Function scores declined over time, consistent with progression in an end-stage cohort. Benefits were sustained up to 1.5 years in the Poor subgroup, 1 year in the Fair subgroup, and less than 1 year in the Good and Excellent subgroups. CONCLUSIONS: A structured six-session programme was associated with sustained symptom relief in patients awaiting surgery, particularly among those with poorer baseline function. Severity-stratified progression strategies warrant further evaluation in controlled studies. Key Points • A scalable six-session physiotherapy-led programme improved pain and functional outcomes in patients with end-stage knee OA awaiting TKR. • Benefits were sustained for up to 18 months, particularly among patients with poorer baseline knee function. • Baseline severity modified durability of response, suggesting a need for severity-stratified progression and maintenance strategies.
The value of arthroscopic synovectomy in the treatment of rheumatoid arthritis: A prospective cohort study.
Dai LY, Ren JQ, Zhao YQ … +3 more , Zhao JX, Mu R, Yang YP
Clin Rheumatol · 2026 Jun · PMID 42366265 · Publisher ↗
BACKGROUND: The aim of this study is to investigate the effect of arthroscopic synovectomy (AS) on disease status in patients with rheumatoid arthritis (RA). METHODS: A prospective study was conducted among patients with...
BACKGROUND: The aim of this study is to investigate the effect of arthroscopic synovectomy (AS) on disease status in patients with rheumatoid arthritis (RA). METHODS: A prospective study was conducted among patients with RA who underwent AS of the elbow or knee joints due to persistent swelling following conventional treatment, as well as control individuals who only received conventional treatment. All patients were evaluated at baseline and 4, 12, 24, 48, 96 weeks after AS. The coprimary outcomes were week 96 disease activity score (DAS)-28 remission and American College of Rheumatology improvement criteria (ACR20/50/70) remission. Key secondary outcomes were changes from baseline to week 96 in Mayo score, Lysoholm score, Health Assessment questionnaire (HAQ), patient's visual analogue scale, Magnetic Resonance Imaging in AS group. The correlation between synovial tissue biology and clinical response was analyzed. RESULTS: A total of 51 patients were included, with 17 accepted AS and conventional treatment, 34 only accepted conventional treatment. At week 96, more patients in AS group achieved DAS-28 remission [52.9% (9/17) vs 11.8% (4/34), P = 0.005] and ACR70 response [35.3% (6/11) vs 5.9% (2/34), P = 0.021] compared with control group. In AS group, DAS28 score [3.9 (3.7, 4.4) vs 2.8 (2.2, 3.4), P = 0.0002], MAYO score [52.5, (45.3, 62.8) vs 72 (60. 76.3), P = 0.021], Lysoholm score [55.5 (50, 59.5) vs 67.5 (63, 78), P = 0.020] and HAQ [4 (1, 6) vs 1 (0, 2), P = 0.034] improved significantly at week 4, 4, 12 and 48 respectively, and persisted until week 96. An increase in disease activity after AS was exclusively noted in the diffuse myeloid group. CONCLUSION: The disease activity and joint function of RA patients who underwent AS showed considerable improvement after surgery, which suggests that AS may enhance the likelihood of achieving remission in patients who had been treated with multiple DMARDs but have not achieved remission. Key Points • The rate of patients achieved disease remission in AS group at week 96 endpoint was better than that of the conventional treatment group. • Patients with RA after AS showed sustained improvement in disease activity and joint function, which remained stable for 96 weeks. • Only patients with diffuse myeloid synovial pathology exhibit increased disease activity.
Social appearance anxiety and its associations with anxiety, depressive symptoms, and health-related quality of life in systemic sclerosis: a cross-sectional study.
Cakir ZT, Akdag A, Tanrikulu D … +4 more , Avcu A, Ergun T, Direskeneli H, Alibaz-Oner F
Clin Rheumatol · 2026 Jun · PMID 42365561 · Publisher ↗
INTRODUCTION/OBJECTIVES: This study aimed to evaluate social appearance anxiety in patients with systemic sclerosis compared with healthy controls and to examine its associations with anxiety, depressive symptoms, health...
INTRODUCTION/OBJECTIVES: This study aimed to evaluate social appearance anxiety in patients with systemic sclerosis compared with healthy controls and to examine its associations with anxiety, depressive symptoms, health-related quality of life, and disease-related clinical features. METHOD: This cross-sectional study included 71 patients with systemic sclerosis and 38 healthy controls. Social appearance anxiety was assessed using the Social Appearance Anxiety Scale. Anxiety and depressive symptoms were evaluated using the Hospital Anxiety and Depression Scale, and health-related quality of life was assessed using the Short Form-36. Disease-related variables, including modified Rodnan skin score and EUSTAR disease activity index, were recorded. RESULTS: Patients with systemic sclerosis had higher Social Appearance Anxiety Scale scores than healthy controls [32.0 (21.0-51.5) vs. 19.0 (16.25-34.0); p = 0.003]. Anxiety and depressive symptom scores were also higher in patients with systemic sclerosis. In systemic sclerosis, social appearance anxiety correlated positively with anxiety symptoms and negatively with several health-related quality-of-life domains. No significant association was observed between social appearance anxiety and modified Rodnan skin score or EUSTAR disease activity index. CONCLUSIONS: Social appearance anxiety is increased in systemic sclerosis and is associated with psychological distress and impaired health-related quality of life rather than conventional disease activity or skin thickness measures. These findings support incorporating psychosocial assessment into routine systemic sclerosis care. Key Points • Patients with systemic sclerosis had higher social appearance anxiety than healthy controls. • Social appearance anxiety was associated with anxiety symptoms and impaired health-related quality of life. • Social appearance anxiety was not significantly associated with skin thickness or EUSTAR disease activity. • Psychosocial assessment may provide clinically relevant information in systemic sclerosis care.
Enhancing the treat-to-target approach of inflammatory arthritis with purposeful shared decision-making: results of a randomized controlled trial.
El Miedany Y, Elgaafary M, Plummer S … +6 more , Bahlas S, Mahran S, Palmer D, Hassan W, Elwakil W, El Miedany A
Clin Rheumatol · 2026 Jun · PMID 42365560 · Publisher ↗
BACKGROUND: Purposeful SDM (PSDM) is a problem-based approach that emphasizes the multifaceted nature of SDM in response to different settings and contexts. OBJECTIVE: To evaluate the effectiveness of a novel approach ut...
BACKGROUND: Purposeful SDM (PSDM) is a problem-based approach that emphasizes the multifaceted nature of SDM in response to different settings and contexts. OBJECTIVE: To evaluate the effectiveness of a novel approach utilizing patient decision aids in facilitating purposeful shared decision-making within the context of rheumatology care. METHODOLOGY: This randomized controlled study included 431 patients diagnosed with inflammatory arthritis. The patients were randomized to receive management according to either the traditional standard care protocol (215 patients) or the purposeful shared decision-making (PSDM) approach (216 patients), which utilizes structured communication tools. At the end of 1 year of intensive therapy, 6 key outcomes were be assessed to measure the impact of PSDM: clinical remission, medication adherence, treatment cessation, patient motivation, multidisciplinary engagement (contact and utilization rates of the helpline facility), and comprehensibility. RESULTS: At 12 months of treatment, 84.3% of the PSDM group achieved treatment target scores, which was significantly higher than the control group, where 62.3% achieved the target. The patients' adherence to anti-rheumatic therapy, as well as comprehensibility, was significantly higher (p < 0.1) in the PSDM group in comparison to the control group (p < 0.01). Patient motivation scores were significantly higher in the PSDM group (p < 0.01). The percentage of patients who contacted the help line from the control group was significantly higher, in contrast to the PSDM group (p < 0.01). CONCLUSION: Using rheumatology-specific PSDM tools aids in improving patients' knowledge and supporting communication with their clinicians on treatment benefits and risks. PSDM strategies may improve implementation of the treat-to-target approach. Addressing the variable modes of shared decision-making beyond weighing treatment options improves patients' understanding of the disease. Key Points • Shared decision-making (SDM), a collaborative process where clinicians and patients jointly arrive at meaningful healthcare decisions. • Purposeful Shared Decision-Making (PSDM) is a problem-based approach that acknowledges the multifaceted nature of SDM, adapting its application to diverse settings, patient needs, and decision types. • A PSDM framework, supported by patient decision aids, demonstrably improves critical outcomes in patients with inflammatory arthritis and spondyloarthritis. • By fostering deeper patient understanding, increasing adherence, boosting motivation, and reducing reliance on external support, PSDM facilitates better disease control and patient empowerment.
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