Clinical Rheumatology[JOURNAL]
Sun
200 papers
Two curious cases of muscle weakness secondary to sarcoidosis: Sarcoid myopathy, a rare entity.
Castañeda Pérez S, Vázquez Temprano N, Fernández Argüeso A … +5 more , Astor Molero S, Martín-Aragón CM, Diéguez Paz J, Pernas Pardavila H, Alves Pereira ED
Reumatol Clin (Engl Ed) · 2026 · PMID 42342314 · Publisher ↗
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Radon balneotherapy in rheumatologic diseases: potential mechanisms and implications for cardiovascular autonomic control and inflammation.
Rodrigues GD, Lee E, Dugué B … +11 more , Hanshans C, Maccarone MC, Triantafyllias K, Hartl A, Kaniusas E, Mörkl S, Schmid TE, Mickeviciute GC, Untner H, Klingler W, Offenbächer M
Clin Rheumatol · 2026 Jun · PMID 42340546 · Publisher ↗
Radon balneotherapy, a form of low-dose radiation treatment, has been utilized for decades in managing rheumatologic diseases, particularly in Central Europe and parts of Asia. Despite ongoing debate about its efficacy,...
Radon balneotherapy, a form of low-dose radiation treatment, has been utilized for decades in managing rheumatologic diseases, particularly in Central Europe and parts of Asia. Despite ongoing debate about its efficacy, developing research suggests that low-dose exposure to radon may exert anti-inflammatory and analgesic effects, with potential implications for musculoskeletal and cardiovascular health. This narrative review aims to synthesize current knowledge on the biological mechanisms underlying radon therapy, evaluate clinical evidence for its efficacy in rheumatologic conditions, and explore its potential impact on cardiovascular health. Risks, controversies, and regulatory restrictions are also addressed. Preclinical studies indicate that radon therapy modulates oxidative stress responses, immune signalling cascades, and pro-inflammatory cytokine profiles, thereby influencing tissue homeostasis and pain perception. Clinically, benefits have been observed in patients with rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis, particularly with respect to pain alleviation, functional improvement, and quality of life. However, heterogeneity in treatment protocols, study quality, and confounding factors such as the use of heat, carbon dioxide, and/or other concurrent modalities limit generalizability and attributability. Evidence regarding cardiovascular safety remains sparse but suggests that low-dose exposure may have neutral or even protective effects under specific physiological conditions. In summary, radon balneotherapy may have a complementary role alongside other modalities like heat and negative air ions. However, the isolated therapeutic efficacy, long-term safety profile, and cardiovascular implications of radon balneotherapy remain insufficiently characterized. Higher quality multi-armed randomized controlled trials and isolated mechanistic investigations are needed to better delineate its biological mechanisms, optimize protocols, and define its clinical niche.
Urate-lowering therapy adherence among gout patients in Southwest China: A cross-sectional study of determinants and regional disparities.
Tang Z, Huang C, Qiu G … +5 more , Wei G, Ling X, Wu J, Wang P, Chen J
Clin Rheumatol · 2026 Jun · PMID 42337134 · Publisher ↗
OBJECTIVE: Gout is directly associated with hyperuricemia. This study aims to investigate the adherence rate to urate-lowering therapy (ULT) and its influencing factors among patients with gout in Southwest China. METHOD...
OBJECTIVE: Gout is directly associated with hyperuricemia. This study aims to investigate the adherence rate to urate-lowering therapy (ULT) and its influencing factors among patients with gout in Southwest China. METHODS: A cross-sectional study was conducted involving 1023 gout patients treated at the Affiliated Hospital of Southwest Medical University between January 2022 and June 2025. Data were collected through telephone follow-ups and electronic medical record reviews. The Adherence to Refills and Medications Scale (ARMS) was used to assess ULT adherence among gout patients. A multivariate binary logistic regression model was used to analyze the correlation between independent variables. RESULTS: The ULT adherence rate among gout patients was 31.6%. Multivariate binary logistic regression analysis revealed that smoking and alcohol consumption were independently associated with poor ULT adherence. Concurrent hypertension, concurrent diabetes, frequency of follow-up visits (> 3 times/year), confidence in maintaining serum uric acid within the normal range, awareness that the target serum uric acid level for ULT is 360 μmol/L, awareness that urate-lowering drugs should be taken long-term, and awareness that increased low-fat dairy intake benefits gout treatment were independently associated with good ULT adherence. CONCLUSION: Adherence to ULT in Southwest China remains suboptimal but is higher than previously reported rates in other Chinese regions. We identified several modifiable factors-particularly disease knowledge, follow-up frequency, and lifestyle habits-that represent actionable targets for interventions to improve gout management in this underserved population. Key Points • The current status of ULT adherence among gout patients is suboptimal, and no existing surveys have examined ULT adherence rates among gout patients in Southwest China. • Our research findings indicated that the ULT adherence rate among gout patients was 31.6%. • Smoking and alcohol consumption were negatively associated with ULT adherence, whereas comorbid hypertension, diabetes, follow-up frequency exceeding three times per year, confidence, and gout-related knowledge were positively associated with improved ULT adherence.
Real-world evidence on JAK inhibitors in rheumatology practice: comparative safety, efficacy, and outcomes between JAK inhibitors.
Deniz R, Yılmaz A, Boncukcuoğlu AE … +7 more , Bektaş E, Altıntaş RM, Tan HC, Uğur K, Özköse GG, Kalkan K, Bes C
Clin Rheumatol · 2026 Jun · PMID 42334786 · Publisher ↗
OBJECTIVES: Janus kinase inhibitors (JAKinibs) are increasingly used in rheumatic diseases, yet comparative real-world data on retention, safety, and prescribing patterns remain limited. We evaluated drug survival, adver...
OBJECTIVES: Janus kinase inhibitors (JAKinibs) are increasingly used in rheumatic diseases, yet comparative real-world data on retention, safety, and prescribing patterns remain limited. We evaluated drug survival, adverse events, and discontinuation for three JAKinibs. METHODS: This retrospective, three-arm comparative cohort included patients with rheumatic diseases who received ≥ 1 JAKinib between May 2020 and July 2025. RESULTS: We included 185 patients(median age 44 years, 67.0% female) with seropositive RA (n = 87), seronegative RA (n = 36), ankylosing spondylitis (n = 39), psoriatic arthritis(n = 17), and others(n = 6). Tofacitinib was prescribed in 94 patients(50.8%), baricitinib in 45 (24.3%), and upadacitinib in 69 (37.3%). Most (89.7%) received one JAKinib. Tofacitinib, baricitinib, and upadacitinib were initiated as first JAKinib in 95.7%, 86.7%, and 81.2% of cases, respectively(p = 0.012). At last follow-up, 58.9% remained on any JAKinib. Six-month survival was 81.9% for tofacitinib, 77.8% for baricitinib, and 69.6% for upadacitinib(p = 0.049); median survival was 16.5, 17, and 11 months, respectively (p < 0.001). Secondary non-response was the leading cause of discontinuation, with adverse events accounting for less than 10%. CONCLUSION: JAKinibs showed favourable retention and safety. Treatment sequencing and early access influenced persistence; tofacitinib predominated due to early availability and prior use in biologic-naive patients, while upadacitinib was mainly prescribed after advanced therapy failure yet remained effective in refractory cases. Key Points • JAKinibs remain effective and tolerable across a range of inflammatory rheumatic diseases,regardless of prior biologic exposure or treatment line. • Upadacitinib, although often prescribed after failure of multiple advanced therapies andother JAKinibs, showed high continuation and retention rates, highlighting its role as a viablelate-line option. • Secondary unresponsiveness is the primary barrier to long-term JAKinib persistence,suggesting a need for early recognition and individualized treatment.
Promoting the utilization of rheumatologic musculoskeletal anatomy: a 50-year travel log.
Kalish RA, Wohlgethan JR, Liu N … +11 more , Nemegyei JA, Villaseñor-Ovies P, Saavedra MÁ, Hernández-Díaz C, Navarro-Zarza JE, Pascual-Ramos V, Naredo E, Olivas-Vergara O, Murillo-González J, Mérida-Velasco JR, Canoso JJ
Clin Rheumatol · 2026 Jun · PMID 42334785 · Publisher ↗
This report traces the authors' long journey toward a deeper understanding of the anatomical basis of rheumatologic physical examination. Fifty years ago, one of the authors was struck by the prevalence of subcutaneous a...
This report traces the authors' long journey toward a deeper understanding of the anatomical basis of rheumatologic physical examination. Fifty years ago, one of the authors was struck by the prevalence of subcutaneous and deep bursitis and regional musculoskeletal pain syndromes at his new workplace, prompting studies of bursal swelling, lubrication, and the dynamics of distended superficial and deep bursae. Subsequently, a deficiency in anatomical knowledge was noted across multiple workshops at the American College of Rheumatology and elsewhere. Later, in a different setting, musculoskeletal anatomy workshops were held, based on cross-examination between rheumatology learners and instructors. Palpation was used in the upper extremity, and the spine and lower extremity were demonstrated through motion and self-palpation. Pre-workshop tests consistently revealed poor recall of musculoskeletal anatomy among trainees and practitioners, including orthopedic trainees. All questions were rated highly important in an international Delphi survey of anatomical items relevant to rheumatology. Subsequently, a self-examination method was developed to allow learners to practice, in privacy, the anatomical knowledge traditionally acquired. More recently, an international, unfunded, and enthusiastic study group comprising anatomists, rheumatologists, and ultrasonographers made independent observations of defined neck and upper extremity structures, including the elusive lower belly of omohyoid, the dorsal forearm muscle-tendon intersection, the concurrent contraction of anconeus and pronator teres, and dynamic aspects of the extensor apparatus of the fingers, the natatory ligament, the web spaces, and the intertendinous connections. In these studies, physical examination and ultrasound complemented each other. Thus, physical examination, rather than being replaced, should be strengthened. Key Points • We describe a sustained effort spanning more than 50 years to reinstate MSK anatomy as a basic competence for MSK conditions and general rheumatologic examination. • The initial studies focused on subcutaneous and deep bursae and on seminars regarding musculoskeletal pain syndromes and, much later, the anatomical basis of rheumatologic examination. • This was followed by a one-on-one assessment of rheumatology fellows' and practitioners' anatomical knowledge and by participatory MSK anatomy seminars held across the Americas with support from ILAR. • Subsequently, a method of self-examination was developed as an accessible way to reinforce anatomical learning. • Currently, independent physical examination and ultrasonography, along with dissection performed by anatomists, have resulted in a series of innovative and fruitful proof-of-concept studies.
The mirror of illness: identity, embodiment, and clinical care in systemic sclerosis.
Gokcen N
Clin Rheumatol · 2026 Jun · PMID 42334784 · Publisher ↗
Systemic sclerosis (SSc) is a complex autoimmune disease characterized by progressive fibrosis, vasculopathy, and multisystem involvement. While clinical assessment appropriately emphasizes measurable outcomes such as or...
Systemic sclerosis (SSc) is a complex autoimmune disease characterized by progressive fibrosis, vasculopathy, and multisystem involvement. While clinical assessment appropriately emphasizes measurable outcomes such as organ involvement and survival, these metrics do not fully capture the lived experience of the disease. This perspective examines how SSc reshapes embodiment, identity, and patient experience beyond conventional clinical measures. Drawing on insights from literature and narrative medicine, it explores themes of bodily estrangement, identity disruption, and adaptation in chronic illness. These dimensions have direct implications for patient-physician communication, treatment adherence, and shared decision-making. Integrating narrative awareness into rheumatology practice may enhance clinicians' ability to recognize psychosocial burden and align care with patient values. A more comprehensive approach to systemic sclerosis, therefore, requires attention not only to measurable disease parameters but also to the meanings patients attach to bodily change and identity over time.
Retiform purpura and blue toe: an unusual presentation of systemic lupus erythematosus.
Ribero Vargas DA, Ayala Monroy GA, Gómez Cerón LN … +2 more , Aguilar Gómez M, Ríos Díaz EJ
Clin Rheumatol · 2026 Jun · PMID 42329349 · Publisher ↗
Retiform purpura (RP) is a morphological pattern of cutaneous ischemia resulting from vascular compromise. Its clinical relevance lies in its orientation toward vasculitis or thrombotic vasculopathy. We report the case o...
Retiform purpura (RP) is a morphological pattern of cutaneous ischemia resulting from vascular compromise. Its clinical relevance lies in its orientation toward vasculitis or thrombotic vasculopathy. We report the case of a woman with painful violaceous retiform lesions on the distal lower extremities, Raynaud's phenomenon with a "blue toe" on the hand, and polyarthralgias. Laboratory workup revealed antinuclear antibodies (ANA) 1:2560 (AC-5 pattern), anti-RNP > 240 U/mL, anti-Sm > 320 U/mL, low C4, and negative antineutrophil antibodies (ANCA) and rheumatoid factor. Magnetic resonance imaging showed diffuse muscular edema and bilateral fascial thickening; computed tomography reported reactive adenopathies. Skin biopsy demonstrated ischemic changes consistent with small vessel involvement in a mixed vasculitic/vasculopathic pattern, with epidermal necrosis and intraluminal fibrin. Systemic lupus erythematosus (SLE) with features of small vessel vasculitis was diagnosed. Treatment included methylprednisolone and prednisone pulses, cyclophosphamide, rituximab, and alprostadil for digital ischemia, with clinical improvement. RP may reflect a mixed inflammatory/thrombotic process in the context of overlapping autoimmunity. Deep biopsy, autoimmune profiling, and assessment of prothrombotic state are key axes for decisions regarding immunosuppression and/or antithrombotic strategies. Key Points • Retiform purpura is a high-risk cutaneous pattern that requires early differentiation between vasculitis and thrombotic vasculopathy, as each condition demands divergent therapeutic strategies (immunosuppression versus antithrombotic therapy). • In patients with SLE, cutaneous vasculitis - though uncommon - may present with a dominant ischemic phenotype (retiform purpura, digital ischemia) that initially mimics medium-vessel vasculitis such as polyarteritis nodosa or systemic sclerosis; accurate diagnosis requires integration of clinical, histological, and immunological data. • Management of severe ischemic SLE with a mixed inflammatory/occlusive mechanism may require a parallel approach: intensive immunosuppression to control vascular inflammation, combined with vasoactive and anticoagulant measures to preserve distal perfusion and tissue viability.
Kinesiophobia and physical activity participation in axial spondyloarthritis: a cross-sectional study during the COVID-19 pandemic.
Thompson JR, Goodwin JFS, Vallabhajosula S … +2 more , Baez S, Thoma L
Clin Rheumatol · 2026 Jun · PMID 42329348 · Publisher ↗
OBJECTIVE: To examine the independent association of kinesiophobia with meeting physical activity (PA) guideline recommendations in individuals with axial spondyloarthritis (axSpA). METHODS: This cross-sectional study re...
OBJECTIVE: To examine the independent association of kinesiophobia with meeting physical activity (PA) guideline recommendations in individuals with axial spondyloarthritis (axSpA). METHODS: This cross-sectional study recruited U.S.-based adults with axSpA via online platforms and support groups between October and December 2020, during the COVID-19 pandemic. Participants completed a digital survey including demographic and clinical information and validated outcome measures for kinesiophobia (TSK-11), disease activity (BASDAI), function (BASFI), quality of life (ASQoL), and PA participation. PA participation was categorized as meeting American College of Sports Medicine (ACSM) guidelines for moderate, vigorous, and strengthening activity. Logistic regression models assessed the association of TSK-11 scores with meeting ACSM PA recommendations, adjusting for age, sex, disease duration, and disease activity. RESULTS: 180 participants completed the survey. Overall, 31%, 26%, and 34% met ACSM guidelines for moderate, vigorous, and strengthening activity, respectively. Higher kinesiophobia was significantly associated with reduced odds of meeting PA guidelines across all activity types. In adjusted models, sample sizes ranged from 141 to 142 participants across activity outcomes due to incomplete data; each one-point increase in TSK-11 was associated with 11% lower odds of meeting strengthening activity guidelines (OR = 0.89, 95% CI: 0.83-0.96), 8% lower odds for meeting moderate activity guidelines (OR = 0.92, 95% CI: 0.86-0.99), and 9% lower odds for meeting vigorous activity guidelines (OR = 0.91, 95% CI: 0.84-0.98). No covariates included in the adjusted models (age, sex, disease duration, BASDAI) were significant predictors. CONCLUSION: Kinesiophobia was independently associated with lower odds of meeting PA guidelines among individuals with axSpA, beyond demographic and disease-related factors. These findings underscore the need for routine assessment and targeted intervention strategies to address fear-avoidant behaviors in activity and exercise counseling for axSpA. Key Points • Higher levels of kinesiophobia were independently associated with lower odds of meeting moderate, vigorous, and strengthening physical activity recommendations among adults with axial spondyloarthritis. • Most participants did not meet recommended levels of physical activity, with a substantial proportion reporting no participation in vigorous or strengthening activities. • Kinesiophobia may represent a clinically meaningful barrier to physical activity participation and a potential target for intervention in axial spondyloarthritis.
Healthcare utilization and costs in patients with rheumatoid arthritis using biologics or tofacitinib: a nationwide, population-based study.
Chen YJ, Ho WL, Chen HM … +2 more , Chen YM, Chen HH
Clin Rheumatol · 2026 Jun · PMID 42324432 · Publisher ↗
BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease, and the use of biological agents in the treatment of RA in recent years has significantly improved RA disease activities and clinical outc...
BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease, and the use of biological agents in the treatment of RA in recent years has significantly improved RA disease activities and clinical outcomes. However, the greatly increased medical costs due to the high costs of biologics are a major concern. We aimed to investigate healthcare utilization and costs in patients with RA pre- to post-initiation of biologics or tofacitinib. METHODS: We conducted a nationwide, population-based study from 1996 to 2017 using Taiwan's National Health Insurance Research Database (NHIRD). In total, 57,084 newly diagnosed RA patients aged ≥ 20 years were identified, of whom 10,566 patients using biologics or tofacitinib were selected and included in the final analysis. The dose adjustments of anti-rheumatic drugs and healthcare utilization and costs among RA patients 3 months before and 6 months after use of biologics were compared. Additionally, a sensitivity analysis evaluating healthcare utilization and costs over a 12-month period pre- to post-initiation of biologics or tofacitinib was conducted. RESULTS: RA patients had more frequent all-cause and RA-related outpatient department (OPD) visits after receiving biologics or tofacitinib, but fewer RA-related emergency room (ER) visits (0.00 ± 0.04 times/month, p = 0.005). There were fewer OPD visits and lower OPD healthcare costs in RA patients using tocilizumab (OPD visits: β - 0.20, p = 0.013; OPD costs: β - 16,366.92, p < 0.001) and abatacept (OPD visits: β - 0.41, p < 0.001; OPD costs: β - 4436.24, p < 0.001), compared with etanercept users. Moreover, significant dose reductions of concomitant anti-rheumatic drugs were observed in RA patients after biologics or tofacitinib, including corticosteroid, leflunomide, hydroxychloroquine, and cyclosporin. Between 10.8 and 47.0% of RA patients experienced a reduction in the dose of anti-rheumatic drugs. CONCLUSIONS: This nationwide, population-based study revealed that the dose of concomitant anti-rheumatic drugs and RA-related ER visits significantly reduced after initiating biologics or tofacitinib. Compared with etanercept users, patients treated with tocilizumab or abatacept had significantly lower outpatient care-related visit numbers and costs. Key Points • This nationwide population-based study investigated healthcare utilization and costs in RA patients pre- to post-initiation of biologics or tofacitinib. • RA-related emergency room visits and doses of concomitant anti-rheumatic drugs significantly declined after starting biologic or tofacitinib therapy, suggesting improved disease control. • Tocilizumab and abatacept use were associated with fewer outpatient visits and lower costs than etanercept, offering more resource-efficient options for certain patients. • Older age, male sex, and higher comorbidity burden predicted more dose reduction of conventional anti-rheumatic medications, supporting individualized treatment planning and de escalation strategies in clinical practice.
Clinical characteristics and disease activity of Spondyloarthritis in Central Vietnam: a cross-sectional study.
Van Nguyen HT, Vo THH, Le CT … +2 more , Nguyen TTT, Nguyen TKO
Clin Rheumatol · 2026 Jun · PMID 42322542 · Publisher ↗
INTRODUCTION: Spondyloarthritis (SpA) is a major cause of chronic pain and disability worldwide; however, clinical characterization remains limited in Southeast Asia, particularly in low- and middle-income countries. Thi...
INTRODUCTION: Spondyloarthritis (SpA) is a major cause of chronic pain and disability worldwide; however, clinical characterization remains limited in Southeast Asia, particularly in low- and middle-income countries. This study aimed to describe the epidemiological and clinical characteristics of SpA in Central Vietnam. METHODS: We conducted a cross-sectional study of patients diagnosed with SpA according to the Assessment of SpondyloArthritis International Society criteria from 2019 to 2024. Disease activity was evaluated using the Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and the Patient Global Assessment (PGA). Factors associated with ASDAS-CRP and PGA score were explored using linear regression models. RESULTS: Based on an analaysis of 177 patients with SpA, the following results were observed. Most patients (148) had axial SpA, while 29 (16.4%) had peripheral SpA. Males accounted for 66.7% of cases, and 95.5% were diagnosed before the age of 45 years. The mean ASDAS-CRP and PGA scores were 2.8 ± 1.1 and 5.1 ± 2.1, respectively. Overall, 57% of patients exhibited high or very high disease activity. Higher ASDAS-CRP scores were significantly associated with male sex, presence of enthesitis, CRP ≥ 5 mg/L, ESR ≥ 10 mm/h, and absence of anemia. Higher PGA scores were significantly associated with older age at diagnosis, presence of enthesitis, chronic enteritis, CRP ≥ 5 mg/L, and absence of anemia. CONCLUSION: This study highlights a male predominance and a higher proportion of axial over peripheral SpA in Central Vietnam. Most patients presented with moderate to high disease activity. These findings emphasize the need for early diagnosis and management, as well as larger multi-center studies to better define the epidemiology and clinical patterns of SpA in Vietnam. Key Points • Provides the first comprehensive clinical characterization of spondyloarthritis (SpA) in Central Vietnam. • Reveals a clear predominance of axial SpA and male patients in the Vietnamese population. • Identifies factors associated with higher disease activity using both ASDAS-CRP and Patient Global Assessment. • Emphasizes the need for early diagnosis and multicenter studies to improve SpA management in Southeast Asia.
Multidimensional immunoinflammatory profiles associated with rheumatoid arthritis-associated interstitial lung disease: a cross-sectional exploratory study.
Zhao Y, Guan Z, Peng L … +3 more , Zhong R, Liu M, Chen X
Clin Rheumatol · 2026 Jun · PMID 42322541 · Publisher ↗
OBJECTIVE: To investigate the associations of non-invasive peripheral blood inflammatory indices, cytokines, and lymphocyte subsets with the risk of rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD)...
OBJECTIVE: To investigate the associations of non-invasive peripheral blood inflammatory indices, cytokines, and lymphocyte subsets with the risk of rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD), and to evaluate the auxiliary diagnostic discrimination of key biomarker panels. METHODS: This retrospective study enrolled 216 eligible patients (148 with RA alone, 68 with RA-ILD). After 1:1 propensity score matching (PSM), 114 patients were included. Variables were screened using the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression. A nomogram was developed and internally validated, with discriminative performance and calibration assessed by the area under the receiver operating characteristic curve (AUC), calibration curves, and bootstrap resampling. An exploratory ROC-derived cutoff of the model-predicted probability was further determined using the Youden index. An (extreme gradient boosting) XGBoost model was further constructed and combined with Shapley Additive exPlanations (SHAP) analysis for performance comparison and interpretability evaluation. RESULTS: In multivariable analysis, CD4⁺ T cells, the systemic inflammation response index (SIRI), and the interleukin (IL)-2/IL-6 ratio were independently associated with RA-ILD. Restricted cubic spline (RCS) analyses confirmed that CD4⁺ T cells and the IL-2/IL-6 ratio exhibited non-linear correlations with RA-ILD risk, whereas SIRI showed an approximately linear positive trend. The nomogram achieved an AUC of 0.820, compared with 0.947 for the XGBoost model. A model-predicted probability cutoff of 0.494, corresponding to a nomogram score of 111.25 points, was associated with higher odds of RA-ILD (OR = 10.40, 95% CI: 4.51-25.59). SHAP analysis identified the IL-2/IL-6 ratio, SIRI, IFN-γ/IL-4 ratio, IL-17A, and CD4⁺ T cells as the leading contributors to model output. CONCLUSION: Peripheral blood immune and inflammatory biomarkers are closely related to RA-ILD risk. The combination of peripheral blood immune and inflammatory biomarkers shows favorable discriminatory value and may provide a laboratory-based reference for auxiliary identification of RA-ILD. Key Points • This study explored RA-ILD from a multidimensional peripheral blood immune-inflammatory perspective. • CD4⁺ T cells, SIRI, and the IL-2/IL-6 ratio emerged as key variables in the multivariable analysis. • CD4⁺ T cells and the IL-2/IL-6 ratio showed non-linear associations with RA-ILD risk, whereas SIRI showed an approximately linear positive association. • The proposed models showed potential for RA-ILD risk assessment and warrant further validation.
The mediating effects of plasma proteome on the association between selenium and systemic lupus erythematosus.
Chen Z, Chen Y, Li J … +5 more , Sun X, He Z, Wen C, Mao Y, Ye D
Clin Rheumatol · 2026 Jun · PMID 42322540 · Publisher ↗
OBJECTIVES: Previous studies have indicated that elevated selenium levels curb systemic lupus erythematosus (SLE) risk, whereas the specific mechanisms remain to be elucidated. Thereby, our study is conducted to explore...
OBJECTIVES: Previous studies have indicated that elevated selenium levels curb systemic lupus erythematosus (SLE) risk, whereas the specific mechanisms remain to be elucidated. Thereby, our study is conducted to explore the mediating function of proteome on the association between selenium and SLE. METHODS: Summary data for plasma proteins came from six large-scale genome wide association studies (GWASs). The data of selenium were derived from a GWAS meta-analysis involving 9639 individuals, and those with SLE were obtained from SLE meta-GWASs (5206 cases and 9066 controls). Two-sample Mendelian randomization (MR) was performed using inverse-variance weighting (IVW), followed by a series of sensitivity analyses to examine the causal relationship between plasma proteins and SLE. Additionally, a two-step MR (TSMR) analysis was applied to explore the mediating role of plasma proteins in the link between selenium and SLE. Moreover, multivariable MR (MVMR) was utilized to adjust and calculate the mediating effect, revealing the potential mechanisms underlying the impact of selenium on SLE. RESULTS: In the MR analysis, we found 24 plasma proteins associated with SLE among 4372 unique plasma proteins. Notably, three plasma proteins exhibited a causal link with selenium. Through mediation analysis, we identified sex hormone-binding globulin (SHBG) mediated the causal effect between selenium and SLE. Specifically, increased selenium levels could lower SLE risk by reducing SHBG levels, with a mediation proportion of 22% (95% CI 13-54%). CONCLUSIONS: This research highlights the key mediating role of plasma proteins in the association between selenium and SLE, which elucidates the targeted protein as SHBG for the relationship. Key Points • The research genetically predicted a causal link between plasma proteins and SLE. • The study revealed that plasma proteins mediate the relationship between selenium and SLE. • The findings offer new perspectives and potential intervention targets for SLE prevention through SHBG.
Awareness of rheumatoid arthritis symptoms and complications among the Jordanians.
Al Zo'ubi M
Clin Rheumatol · 2026 Jun · PMID 42319620 · Publisher ↗
BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease affecting synovial joints and extra-articular systems. Public recognition of early symptoms, complications, and misconceptions is import...
BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease affecting synovial joints and extra-articular systems. Public recognition of early symptoms, complications, and misconceptions is important for timely help-seeking. OBJECTIVE: To assess public awareness of RA articular symptoms and extra-articular complications in Jordan, identify misconceptions, evaluate intended healthcare-seeking behavior, determine predictors of awareness, and examine questionnaire psychometric performance. METHODS: A cross-sectional online survey using nonprobability, quota-based recruitment through social media and messaging-application advertisements was conducted among adults across all Jordanian governorates between February 10 and March 24, 2026. The cleaned analytic sample included 2332 respondents. Awareness was assessed using six symptom items and five complication items, with scores transformed to a 0-100 scale. Adequate awareness was defined as correct identification of at least 6 of 11 awareness items. Misconception burden was calculated from four items. Multivariable regression identified predictors of awareness and appropriate intended action. Internal consistency and exploratory factor analysis evaluated questionnaire performance. RESULTS: The mean total awareness score was 54.4 (SD, 33.5), and 56.3% of respondents had adequate awareness. Symptom awareness was slightly higher than complication awareness (mean scores, 56.9 vs. 51.4). Joint pain (73.1%), subcutaneous nodules (68.2%), and joint deformity (64.3%) were most recognized, whereas eye inflammation (29.7%), morning stiffness (45.5%), and small-joint swelling (46.5%) were less frequently identified. Misconceptions were common: 46.7% believed RA is not serious, 34.9% endorsed herbal cure beliefs, and 30.5% confused RA with osteoarthritis. Only 40.4% selected an appropriate intended action. Prior awareness of RA, knowing someone with RA, and higher education were the strongest predictors of awareness. Symptom and complication subscales showed good internal consistency (Cronbach's alpha, 0.806 and 0.799), and exploratory factor analysis supported a dominant general awareness factor. CONCLUSION: RA awareness in Jordan was moderate but uneven, with better recognition of visible joint manifestations than early inflammatory symptoms and extra-articular complications. Misconceptions were frequent, and appropriate intended help-seeking was reported by fewer than half of respondents. Interventions should frame RA as a serious, treatable systemic autoimmune disease and emphasize early warning signs, extra-articular complications, misconception correction, and medical consultation. Key Points • Overall, RA awareness was moderate, with a mean total awareness score of 54.4%, and 56.3% of participants meeting the predefined threshold for adequate awareness. • Participants recognized visible or general joint manifestations better than early inflammatory features; joint pain was most recognized, while morning stiffness and small-joint swelling were identified by fewer than half of respondents. • Awareness of extra-articular complications was incomplete, especially for eye inflammation and lung involvement, supporting the need to frame RA as a systemic autoimmune disease rather than only a joint disorder. • Misconceptions were frequent, and only 40.4% selected appropriate intended medical consultation, indicating a need for public health awareness campaigns targeting early symptoms, systemic complications, misconception correction, and timely referral.
Comparison of three therapeutic methods of transcutaneous electrical nerve stimulation, embedding acupuncture, and drug therapy on interleukin-6 and pain levels in patients with knee osteoarthritis.
Nematshahi M, Mirhamidi M, Farkhani EM … +4 more , Farahmand SK, Solati S, Tehrani MV, Bahrami Taghanaki H
Clin Rheumatol · 2026 Jun · PMID 42319619 · Publisher ↗
BACKGROUND: Knee osteoarthritis (KOA) significantly impairs quality of life, yet conventional pharmacotherapy often provides inadequate symptom control with notable adverse effects. This randomized controlled trial compa...
BACKGROUND: Knee osteoarthritis (KOA) significantly impairs quality of life, yet conventional pharmacotherapy often provides inadequate symptom control with notable adverse effects. This randomized controlled trial compared thread embedding acupuncture (TEA), transcutaneous electrical nerve stimulation (TENS), and conventional drug therapy on pain, functional disability, quality of life, and serum interleukin-6 (IL-6) levels in KOA patients. METHODS: Seventy-two patients aged 50-65 years with unilateral KOA (Kellgren-Lawrence grades 2-3) were randomly allocated to (1) single TEA session at ten acupoints (n = 24), (2) TENS therapy (50-100 Hz, 30 min, four sessions/week) for 4 weeks (n = 24), or (3) ibuprofen 400 mg twice daily for 4 weeks (n = 24). All received acetaminophen 325 mg daily. Primary outcomes were pain intensity (visual analogue scale) and serum IL-6 levels. Secondary outcomes included WOMAC index and WHOQOL-BREF scores. Assessments occurred at baseline, week 4, and week 12. Data were analyzed using repeated-measures ANOVA and ANCOVA adjusting for baseline age and IL-6. RESULTS: At week 12, TEA showed superior pain reduction (- 1.75 [95% CI: - 2.28 to - 1.21], p < 0.001) versus TENS (- 0.72 [95% CI: - 1.25 to - 0.15], p = 0.01) and drug therapy (0.33 [95% CI: - 0.53 to 1.20], p = 0.45). Quality of life improvements were greatest with TEA (12.83 [95% CI: 6.70 to 18.95], p < 0.001) compared to TENS (5.20 [95% CI: 0.41 to 10.00], p = 0.03) and drug therapy (- 1.25 [95% CI: - 7.18 to 4.68], p = 0.68). TEA and TENS significantly reduced WOMAC scores (- 16.58 and - 11.33, both p < 0.001), unlike drug therapy. Serum IL-6 increased significantly in the TEA group (3.20 pg/mL [95% CI: 1.74 to 4.66], p < 0.001) but not in TENS or drug therapy groups. CONCLUSION: A single TEA session provides superior and sustained improvements in pain, function, and quality of life compared to 4 weeks of TENS or drug therapy in KOA patients. Clinical benefits were associated with elevated serum IL-6, suggesting immunomodulatory mechanisms involving tissue repair pathways. TEA represents a promising integrative approach for KOA management, warranting larger trials with extended follow-up. Key Points • Pain control in knee osteoarthritis, a common disease. • Conventional treatments (such as TENS and medication) have high costs and side effects. • The use of acupuncture and embedding (TEA) can treat pain without any specific complications. • It is also important to examine IL-6 as a factor for which anti inflammatory effects were observed in our study and some studies.
Hughes-Stovin syndrome (HSS) preliminary diagnostic criteria: a paradigm shift in managing pulmonary vasculitis in HSS and Behçet's disease (BD). On behalf of the HSS International Study Group (HSSISG) : Reply on Tahir Saygın Öğüt and Veli Yazısız "Comments on the proposed diagnostic criteria for Hughes-Stovin syndrome: the role of Behçet syndrome" (CLRH-D-26-01350).
Emad Y, Gheita T, Ragab Y … +38 more , Hammam N, Kindermann M, Ibrahim O, Fabi M, Frikha F, Alhusseiny K, Tekavec-Trkanjec J, Kechida M, Farber HW, Young P, Pankl S, Robinson C, Tharwat S, Guffroy A, Jaramillo N, Ruffer N, Bawaskar P, Kably I, Abou-Zeid A, Hassan M, Ghirardo S, Barman B, Bennji S, Agarwala MK, Tornes L, Margolesky J, Silva RS, Cruz V, Abdelbary MH, Kim JT, Cozzi D, Abdelali M, Joy TC, Sherwina J, Kassem IA, Yasser F, Ten Klooster PM, Rasker JJ
Clin Rheumatol · 2026 Jun · PMID 42319618 · Publisher ↗
Hughes-Stovin syndrome (HSS) is a rare and aggressive type of systemic vasculitis which is characterized by peripheral venous thrombosis and pulmonary artery aneurysms (PAAs) at the onset of the disease, as well as the a...
Hughes-Stovin syndrome (HSS) is a rare and aggressive type of systemic vasculitis which is characterized by peripheral venous thrombosis and pulmonary artery aneurysms (PAAs) at the onset of the disease, as well as the absence of recent or previous attacks of uveitis. The onset of HSS and its dominant clinical disease presentations differ in many aspects from those observed in Behçet's disease (BD). The absence of uveitis is a mandatory exclusion criterion in the preliminary diagnostic criteria proposed by the HSS International Study Group (HSSISG), to avoid misclassification between HSS and BD. The presence of PAAs is an obligatory "entry criterion" for diagnosis, while vascular thrombotic events are a "major criterion" after excluding other causes of coagulopathy-induced thrombosis. The HSSISG regards HSS and BD as one disease, yet exhibiting distinct patterns of disease expression, particularly at disease onset. Differentiating HSS from BD is especially important for early diagnosis and optimal management. While the presence of HLA-B51 is the strongest genetic risk factor for BD, it is not used as a criterion to confirm a diagnosis because it lacks sufficient specificity. The prevalence of HLA-B51 in HSS is relatively low, suggesting that different genetic drivers might exist or that HSS is a unique entity with overlapping features with BD. In HSS, both HLA-B51 positive and negative cases have been described; thus, it cannot be a hallmark of the syndrome, and it does not play a role in the diagnostic criteria.
The effect of biologic disease modifying anti-rheumatic drugs on the neutrophil-lymphocyte ratio in psoriatic arthritis patients.
Lauran M, Kyeremateng C, Haque A … +4 more , Rizal S, Ahmed H, Pandey S, Nisar MK
Clin Rheumatol · 2026 Jun · PMID 42319617 · Publisher ↗
OBJECTIVES: Cardiovascular mortality is up to 43% greater in patients with Psoriatic Arthritis (PsA) when compared to the general population. Whilst composite cardiovascular disease risk prognosticators exist, an emergin...
OBJECTIVES: Cardiovascular mortality is up to 43% greater in patients with Psoriatic Arthritis (PsA) when compared to the general population. Whilst composite cardiovascular disease risk prognosticators exist, an emerging inexpensive biomarker known as the neutrophil-lymphocyte ratio (NLR) has been demonstrated to be a risk-associated biomarker of cardiovascular disease (CVD) in the general population. This study therefore aimed to assess the effect of biologic disease modifying antirheumatic drug (bDMARDs) on the NLR in a cohort of adult patients diagnosed with PsA. METHODS: A retrospective single-centre observational study was conducted using an electronic health record database including 183 adult patients diagnosed with PsA between 1983 and 2024. The NLR of patients was calculated pre- and post-initiation of bDMARDs and statistical significance was analysed using several different statistical analysis tools. RESULTS: The overall number of patients in the higher NLR risk stratification group (NLR > 2) was significantly reduced from 104 to 64 post-biologic initiation. Additionally, there was a statistically significant reduction of 24.0% in the average NLR of the entire patient cohort from 2.58 to 1.96 pre- and post-biologic initiation respectively. CONCLUSION: Our study demonstrates that over a third of patients had a significant NLR reduction post-biologic initiation. The mean NLR of the entire patient cohort demonstrated a shift to a lower CVD risk-associated stratified NLR group (NLR < 2), post-biologic treatment. BDMARD treatment in PsA patients therefore demonstrates a significant reduction in the NLR metric, with a varying degree of theoretical impact on the CVD risk reduction among different biologic drugs and classes. Key Points • bDMARDs reduce the Neutrophil-Lymphocyte Ratio in Psoriatic Arthritis patients. • Both TNF inhibitor and IL-17 inhibitors bDMARDs were associated with significant reductions in the Neutrophil-Lymphocyte Ratio in Psoriatic Arthritis patients.
Targeting RIPK1 is a promising therapeutic avenue for systemic lupus erythematosus.
Chen M, Wan L, Wang M … +5 more , Liang J, Ke Y, Jiang M, Liu J, Cao H
Clin Rheumatol · 2026 Jun · PMID 42319616 · Publisher ↗
BACKGROUND: Necroptosis plays a significant role in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). Nonetheless, the therapeutic potential of necroptosis inhibition in these conditions re...
BACKGROUND: Necroptosis plays a significant role in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). Nonetheless, the therapeutic potential of necroptosis inhibition in these conditions remains unclear. METHODS: This study examines the systemic therapeutic effects of Necrostatin-1 (Nec-1), an inhibitor of receptor-interacting serine/threonine kinase 1 (RIPK1), in MRL/lpr lupus-prone mice. RESULTS: Immunohistochemical analysis in renal tissue of active LN patients and MRL/lpr mice demonstrated elevated levels of pRIPK1 and pMLKL. A 28-day treatment with Nec-1 significantly ameliorated the histological manifestations of SLE, including alopecia, skin erythema, arthritis, and nephritis, in MRL/lpr mice. Notably, it mitigated acute lesion features such as LN perivascular inflammation and reduced the presence of pRIPK1 and pMLKL positive immune cells in the kidney. Mechanistically, Nec-1 treatment may exert its therapeutic effects on SLE by decreasing the proportion of Th17 cells in MRL/lpr mice. CONCLUSION: These findings suggest that targeting RIPK1 hold promise as a therapeutic strategy for the management of SLE. Key Points • Necroptosis markers are upregulated in renal immune cells of active LN patients and MRL/lpr mice. • Necrostatin-1 (Nec-1) ameliorates clinical, serological, and histological features in MRL/lpr mice. • Nec-1 exerts its therapeutic effect by inhibiting necroptosis in immune cells, which subsequently reduces Th17 cell frequency and IL-17A levels.
Pericardial Involvement in Systemic Lupus Erythematosus.
Huang LH, Liu MT
J Clin Rheumatol · 2026 Jun · PMID 42318894 · Publisher ↗
Abstract loading — click title to view on PubMed.
Association between colonoscopic findings and fecal calprotectin levels in familial Mediterranean fever patients with gastrointestinal symptoms: a retrospective cohort study.
Dinçer BT, Urgancı N, Çavuşoğlu M … +2 more , Özçelik G, Usta M
Clin Rheumatol · 2026 Jun · PMID 42313236 · Publisher ↗
INTRODUCTION: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent fever and serositis. Gastrointestinal involvement and subclinical intestinal inflammation have been reported in F...
INTRODUCTION: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent fever and serositis. Gastrointestinal involvement and subclinical intestinal inflammation have been reported in FMF, with elevated fecal calprotectin (FC) levels even during attack-free periods. This study aimed to investigate the relationship between colonoscopic findings and FC levels in pediatric FMF patients presenting with gastrointestinal symptoms. METHODS: This retrospective cohort study included children under 18 years of age with FMF who underwent colonoscopy for gastrointestinal symptoms between 2018 and 2024. Patients were categorized into three groups based on colonoscopic findings: normal colonoscopy, nonspecific findings, and inflammatory bowel disease (IBD). Demographic data, laboratory results, and FC levels were analyzed. ROC analysis was performed to identify the FC cutoff value predictive of colitis. RESULTS: A total of 81 patients (median age 12 years; 51.9% male) were included. FC levels were significantly higher in the IBD group compared to other groups (p < 0.001). Albumin levels were lower in IBD patients (p = 0.013). ROC analysis revealed that an FC level below 123 µg/g predicted normal colonoscopic findings with 89.8% sensitivity and 84.4% specificity (AUC 0.902). CONCLUSION: FC may serve as a useful non-invasive biomarker for predicting colonoscopic abnormalities in pediatric FMF patients. An FC level below 123 µg/g appears to reliably predict normal colonoscopic findings, suggesting that unnecessary invasive procedures may be avoided in this subgroup. Key Points • Fecal calprotectin levels correlated with the severity of colonoscopic abnormalities in FMF patients with gastrointestinal symptoms. • A fecal calprotectin level below 123 µg/g feces strongly predicted normal colonoscopic findings. • Fecal calprotectin may serve as a useful non-invasive tool to reduce unnecessary colonoscopic procedures in pediatric FMF patients.
Integrated bioinformatics and machine learning for shared diagnostic genes and mechanisms between periodontitis and psoriasis.
Wang Q, Fang C
Clin Rheumatol · 2026 Jun · PMID 42313235 · Publisher ↗
BACKGROUND: Periodontitis and psoriasis are two prevalent conditions that are bidirectionally associated. However, the molecular basis remains poorly understood. This study utilized bioinformatics approaches to investiga...
BACKGROUND: Periodontitis and psoriasis are two prevalent conditions that are bidirectionally associated. However, the molecular basis remains poorly understood. This study utilized bioinformatics approaches to investigate the common diagnostic genes and shared mechanisms of periodontitis and psoriasis. METHODS: Classical datasets for periodontitis and psoriasis were sourced from the GEO database. Differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network analysis, and two machine learning algorithms were used to screen common biomarkers. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were utilized to explore biological functions. CIBERSO\ RT was used to assess the immune microenvironment. Transcription factor (TF)-gene and gene-miRNA regulatory networks were analyzed using NetworkAnalyst. RESULTS: 24 DEGs and 333 disease-related genes were identified. Next, three biomarkers (CXCR4, SASH3, and LYN) were identified among the 12 genes shared between DEGs and WGCNA using machine learning. RT-qPCR analysis confirmed the elevated expression of the three shared genes in both conditions. We further constructed a nomogram model and validated it using ROC curves. Immune infiltration analysis revealed a significant association between the three common biomarkers and cellular immune dysregulation. CONCLUSION: CXCR4, SASH3, and LYN are common biomarkers for psoriasis and periodontitis. Additionally, we proposed immune patterns, TF-gene, and gene-miRNA regulatory networks between the two diseases, which could provide new insights for future studies. Key Points • CXCR4, SASH3, and LYN were identified as shared diagnostic biomarkers for periodontitis and psoriasis, validated through bioinformatics and machine learning approaches. • A robust diagnostic model using the three biomarkers demonstrated high accuracy. • Regulatory networks involving key TFs and miRNAs suggest similar mechanisms between periodontitis and psoriasis.
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