Şeyma Türkmen

Introduction: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder. To standardize management, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed three consensus treatment plans (CTPs) (1: methotrexate or sulfasalazine [conventional disease-modifying antirheumatic drugs; DMARDs], 2: tumor necrosis factor (TNF)-alpha inhibitors (TNFi), and 3: bisphosphonates). The Clinical Disease Activity Score (CNO CDAS) was introduced to assess disease activity without relying solely on imaging. Objective: The objectives were to evaluate clinicians’ tendencies in applying CNO-CTPs and to assess treatment responses using CNO CDAS in real-world practice, including therapeutic strategies and outcomes at final follow-up. Methods: A retrospective cohort study of 171 pediatric patients with CNO from 18 centers was conducted. Disease activity was assessed using CDAS at diagnosis, at treatment modification, and at the last visit. This score incorporates clinically active lesions, patient pain, and global assessment. Treatments included NSAIDs, DMARDs, TNFi, and pamidronate. Results: Median age was 10 years at onset and 14 years at last follow-up, with a median follow-up of 36 months. The most frequent symptoms were bone pain (95.3%), activity limitation (67.8%), and fatigue (35.1%). All patients received NSAIDs; methotrexate (85.4%) and TNFi (54.4%) were commonly used. TNF inhibitors were the most used CTP, especially in patients with spinal involvement or higher MRI lesion counts, and they achieved the highest remission rate (40.4%). Of the 89 (52.0%) patients who changed treatment, 93.2% switched from DMARDs to TNFi. At the final follow-up, 62% were in medicated remission, 29.2% were in unmedicated remission, and 8.8% had active disease. CDAS scores significantly improved over time (p < 0.05). Conclusions: CARRA CTPs are effective in clinical practice, with anti-TNF therapy yielding the highest remission rates and marked improvement in CDAS.

Objectives: Anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV) is a rare but potentially life-threatening condition in children, often presenting with severe multi-organ involvement. Although standard induction therapy includes cyclophosphamide or rituximab with glucocorticoids, the role of therapeutic plasma exchange (TPE) in paediatric AAV remains uncertain. This study sought to describe the clinical characteristics, indications and outcomes of paediatric AAV patients treated with TPE in real-world practice and to compare them with patients managed without TPE. Methods: This retrospective multicentre study included children (<18 years) diagnosed with AAV according to EULAR/PRINTO/PRES criteria. Patients were classified into TPE-treated (TPE+) and non-TPE-treated (TPE−) groups. Demographic features, organ involvement, laboratory parameters, Paediatric Vasculitis Activity Score (PVAS), treatments, adverse events and outcomes were analysed. Results: Twenty-six paediatric AAV patients were included, of whom 11 (42.3%) underwent TPE. At diagnosis, the TPE+ group had significantly higher disease activity (median PVAS 12 vs 7, P = 0.004) and more severe kidney involvement, with higher serum creatinine and lower estimated glomerular filtration rate. Severe pulmonary, gastrointestinal, cardiovascular and cutaneous manifestations occurred predominantly in the TPE+ group. The primary indication for TPE was severe kidney involvement. TPE was associated with a significant reduction in PVAS (median 12.0–4.5, P = 0.007). Clinical improvement was observed in most acute organ-threatening manifestations, although persistent abnormalities remained common among patients with severe baseline kidney involvement. One patient died from catheter-related Pseudomonas aeruginosa sepsis during treatment. Conclusion: TPE is selectively used as an adjunctive therapy in children with severe or refractory AAV, particularly in those with advanced kidney involvement. Although disease activity and acute organ-threatening manifestations improved following TPE, persistent renal abnormalities remained frequent, reflecting the severity of baseline kidney disease.

Background/Aims: To compare the clinical characteristics of enthesitis/ spondylitis-related juvenile idiopathic arthritis (E/SpRJIA), a relatively prevalent JIA subtype in Türkiye and India, and to explore potential populationspecific differences in disease expression. Materials and Methods: This multicenter, binational, retrospective cohort study included children fulfilling the provisional PRINTO classification criteria for E/SpRJIA from 12 pediatric rheumatology centers in Türkiye and India. Demographic characteristics, clinical manifestations, human leukocyte antigen B27 (HLA-B27) status, laboratory findings, disease course, and treatment-related data were collected. A multivariable logistic regression analysis was performed to identify factors independently associated with sacroiliitis at diagnosis. Results: A total of 498 patients were included (391 Turkish and 107 Indian). At disease onset, peripheral polyarticular involvement was more common in Indian patients (40.2% vs 5.6%), whereas axial involvement was more frequent in Turkish patients (45.8% vs 18.7%). HLA-B27 positivity was higher in Indian patients than in Turkish patients (79.5% vs 56.4%). During follow-up, sacroiliitis, enthesitis, and tarsitis were more common among Turkish patients, while peripheral arthritis and dactylitis were more frequent among Indian patients. NSAIDs were used more frequently in India, whereas conventional and biologic DMARDs were more commonly used in Türkiye. In multivariable analysis, country of origin remained independently associated with sacroiliitis at diagnosis, whereas HLA-B27 positivity did not. Conclusion: E/SpRJIA demonstrates substantial phenotypic heterogeneity between Turkish and Indian populations. Turkish patients exhibited a predominantly axial disease pattern, whereas Indian patients more commonly showed peripheral polyarticular involvement despite higher HLA-B27 positivity. These findings suggest that factors beyond HLA-B27, including broader genetic, environmental, and population-specific influences, may contribute to differences in disease expression. Further prospective and genetically informed studies are needed to clarify the determinants of this heterogeneity. Cite this article as: İşgüder R, Sharma A, Kızıldağ Z, et al. Comparison of the Clinical Expression of Patients with Enthesitis/Spondylitis-Related Juvenile Idiopathic Arthritis (E/SpRJIA) from Türkiye and India. ArchRheumatol. Published online September 1, 2026. doi: 10.5152/ArchRheumatol.2026.25122.

To characterize clinical features and outcomes of pediatric macrophage activation syndrome (MAS) and examine associations with immune-regulatory genetic variation. This retrospective study included 120 children with MAS. Clinical, laboratory, and outcome data were analyzed. A subgroup underwent genetic testing for Hemophagocytic Lymphohistiocytosis (HLH)-related variants. Multivariable logistic regression identified factors associated with outcomes. Etiologies included multisystem inflammatory syndrome in children (MIS-C) (36.7%), systemic juvenile idiopathic arthritis (sJIA) (26.7%), infection-triggered MAS (23.3%), other rheumatologic diseases (10.8%), and lymphoma (2.5%). Intensive care unit (ICU) admission and acute organ failure occurred in 60% and 45%, and mortality was 17.5%. Compared with sJIA, non-sJIA had higher ICU admission (72.7% vs 25.0%, p= 0.02) and mortality (21.6% vs 6.3%, p= 0.04), whereas recurrence was more common in sJIA (28.1% vs 9.1%, p= 0.04). Stratified analyses (MIS-C, other MAS, and sJIA) showed higher ICU admission in MIS-C and other MAS, highest mortality in other MAS, and highest recurrence in sJIA, with rates of 77.3%, 68.2%, and 25.0% (p< 0.001), 6.8%, 36.4%, and 6.3% (p< 0.001), and 2.3%, 15.9%, and 28.1% (p= 0.01), respectively. Among tested patients, 22.4% carried HLH-related variants. Variant positivity was independently associated with higher ferritin, younger MAS onset, recurrence, acute organ dysfunction, and sJIA aetiology. Higher peak ferritin predicted mortality (OR 2.01) and reduced remission off therapy (OR 0.70), whereas sJIA aetiology was associated with lower mortality (OR 0.21). Pediatric MAS is etiologically heterogeneous, with inflammatory burden and organ dysfunction driving poor outcomes. Immune-regulatory variants are linked to severe or relapsing disease, supporting phenotype-guided stratification.

Objective: To evaluate rare childhood vasculitides using standardized clinical, laboratory, imaging, and outcome data. Methods: A retrospective cohort of 74 children with 8 rare vasculitides was assessed at a single center. Demographics, imaging, and disease activity (Pediatric Vasculitis Activity Score (PVAS)) and damage (Pediatric Vasculitis Damage Index) scores were recorded at diagnosis, 12 months, and last visit. Results: Among 74 patients, 39 (52.7%) were girls. Median diagnosis age was 13.5 years. Subtype distribution was vascular Behçet syndrome 22 (29.7%), Takayasu arteritis (TA) 16 (21.6%), deficiency of adenosine deaminase 2 (DADA2) 14 (18.9%), polyarteritis nodosa 11 (14.9%), granulomatosis with polyangiitis (GPA) 6 (8.1%), primary angiitis of the central nervous system (PACNS) 3 (4.1%), eosinophilic GPA 1 (1.4%), and Cogan syndrome 1 (1.4%). The DADA2 had the longest diagnostic delay (median [IQR]: 20 [6-99.75] months), while PACNS had the youngest median age at onset (4.6 [3.07-7.95] years). Overall, 13.5% (n=10) were diagnosed before age 5, showing recurrent fever (60%, n=6) and anemia (50%, n=5), less skin/mucosal (40%, n=4), musculoskeletal (30%, n=3), cardiovascular (20%, n=2), and pulmonary involvement (20%, n=2), and higher PVAS (median 2.0, IQR 1.25-2.75). At 12 months, all had low disease activity. The TA had the longest corticosteroid use, highest damage, and slower remission. Overall remission was 91.9% (n=68/74), while GPA patients had more flares in the first year (median 1.0, IQR 0.25-1.75). Conclusion: Prognosis was favorable, but TA and monogenic vasculitides showed greater damage. In children <5 years, higher activity but good early response emphasize timely, individualized management.

Musculoskeletal ultrasound (MSUS) has become a cornerstone imaging modality in pediatric rheumatology, providing a safe, non-invasive, and highly sensitive method for assessing musculoskeletal pathology. Reliable interpretation of MSUS requires awareness of developmental anatomy, optimization of technical parameters, and recognition of common artifacts. These considerations are especially important in children, where physiological vascularization and agerelated changes in cartilage or bone can mimic pathology. MSUS enables the detailed visualization of synovitis, tenosynovitis, enthesitis, and early structural abnormalities, often detecting both overt and subclinical inflammation that may be missed on clinical examination. These subclinical observations can offer additional context during follow-up and support more informed decisions in disease monitoring and management. In addition to its diagnostic and prognostic roles, MSUS also enhances interventional approaches. Ultrasound-guided intra articular corticosteroid injections improve precision, safety, and patient comfort compared with landmark-based techniques, while also expanding therapeutic access to joints that are otherwise difficult to inject. Altogether, MSUS is increasingly recognized not only as a complementary tool but as an integral component of juvenile idiopathic arthritis (JIA) management. This review will provide an updated overview of MSUS in the context of JIA, with a particular focus on practical aspects of scanning in children, the differentiation between physiological and pathological findings, the main disease-related sonographic features, and the expanding role of ultrasound in guiding intra-articular procedures. Current challenges, limitations, and future perspectives regarding standardization and integration into clinical care will also be discussed.

Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs, with childhood‐onset SLE (cSLE) typically presenting a more severe course and greater genetic risk than adult‐onset SLE. Although DNA methylation plays a key role in lupus pathogenesis, the epigenetic landscape of cSLE remains understudied. This study aimed to investigate DNA methylation changes in cSLE. Methods: A total of 64 patients with cSLE and 47 healthy control DNA samples isolated from peripheral blood mononuclear cells (PBMCs), along with an independent validation cohort of 38 patient DNA samples from whole blood, were analyzed. DNA methylation was assessed using the Infinium MethylationEPIC version 2.0 array. Methylation differences were tested via linear regression adjusting for age, sex, medication use, and cell composition. Clinical features were compared using the chi‐square test or Fisher's exact test, and Gene Ontology enrichment was conducted. Results: Differential methylation analysis revealed significant hypomethylation in interferon‐regulated genes (eg, DTX3L , PARP9 , IFI44L , MX1 ), enriched in type I interferon–related processes. Hypomethylation in genes linked to B cell activation and senescence correlated with higher SLE Disease Activity Index scores. K‐means clustering identified three distinct methylation‐based cSLE subgroups, each enriched for different biologic processes: cell adhesion and growth factor response (cluster 1), cell differentiation and fate (cluster 2), and oxidative stress and Ras‐associated protein‐1 signaling (cluster 3). Sex‐based analysis showed immune‐related hypomethylation in male patients, with almost 90% of these sites identified in PBMCs also replicating in an independent whole blood dataset. Conclusion: cSLE displays distinct DNA methylation patterns associated with disease activity, molecular subgroups, and sex, underscoring the potential for epigenetically informed diagnostics and therapies. image

To examine the demographic and clinical features of paediatric familial Mediterranean fever (FMF) patients with a heterozygous Mediterranean fever (MEFV) gene mutation, focusing on colchicine discontinuation and factors linked to sustained remission. This retrospective study included 2325 paediatric FMF patients followed at a tertiary rheumatology clinic between August 2016 and February 2024. Of these, 1246 carried a heterozygous MEFV mutation, and 87 had stopped colchicine. Discontinuation was either physician decision (PD) or initiated by family/patient decision (FD). Demographic data, clinical symptoms, colchicine use, and MEFV variants were recorded. Patients were monitored after discontinuation to assess remission and the need for retreatment. Of 87 patients, 47 (54%) were discontinued under PD and 40 (46%) under FD. The median discontinuation age was 10.8 years in PD and 11.7 years in FD. Colchicine was reinitiated in 25 patients (28.7%): 11 (4.0%) from PD and 14 (56.0%) from FD. Drug-free remission was maintained in 62 patients (71.3%), including 36 PD (58.1%) and 26 FD (41.9%) (p = 0.45). The pre-discontinuation asymptomatic period was significantly longer in PD (p < 0.01). PD patients also had a lower risk of reinitiating treatment than FD patients (p = 0.046). Older age at discontinuation was associated with sustained remission (p = 0.01). Colchicine withdrawal under physician supervision and at older ages is associated with a lower risk of relapse and greater likelihood of maintaining drug-free remission.

Objectives: This study evaluated the classification utility of incorporating parotid gland US for juvenile Sjögren’s disease (jSjD) by testing its role in a weighted scoring (WS) model and comparing it with the standard 2016 ACR/EULAR classic model (CM). Methods: Seventeen patients were retrospectively evaluated. All underwent B-mode parotid US at diagnosis, scored via the OMERACT system. Classification scoring items included positivity of anti-SSA, Schirmer test, labial salivary gland biopsy, US (OMERACT score ≥1). The WS (0–8) was calculated according to positivity of each parameter: (anti-SSA × 3) + (biopsy × 3) + (Schirmer × 1) + (US × 1). ROC analysis assessed the WS for predicting ACR/EULAR classification (≥4) and US alone for identifying patients fulfilling ≥2 conventional items (composite score ≥2). The WS was compared with the CM, which excluded US, based on classification performance parameters. Results: The WS yielded an acceptable AUC of 0.72 for predicting fulfilment of the ACR/EULAR classification criteria. US alone showed strong concordance with composite criteria (AUC: 0.84). Although the WS and CM had comparable overall performance (AUC: 0.85 vs 0.87; P = 0.76), the WS achieved higher specificity (92% vs 77%) and positive predictive value (PPV; 86% vs 73%). Conclusion: Although the inclusion of US in the classification model did not significantly improve overall discrimination, it enhanced specificity and PPV, particularly in borderline cases. Given its concordance with conventional criteria and non-invasive nature, US may be a practical candidate for future jSjD classification systems, warranting prospective validation in larger cohorts.

To evaluate the clinical response and observed outcomes, indications, and tolerability of intravenous immunoglobulin (IVIG) therapy in patients with juvenile dermatomyositis (JDM) across a multicenter cohort. This retrospective and multicenter study included 29 patients diagnosed with JDM who received IVIG therapy. Demographic data, disease characteristics, laboratory parameters, and standardized disease activity scores were recorded at disease onset, before and after IVIG treatment, and at final follow-up. Treatment responses and adverse events were analyzed. Intravenous immunoglobulin was initiated a median of 1.2 months (IQR:0.1-18.9) after diagnosis and continued for 8.2 months (IQR:5.6-21.6). Indications included refractory muscle weakness, persistent skin disease, calcinosis, and interstitial lung disease (ILD). IVIG therapy was associated with significant improvements in both disease activity measures and laboratory parameters (p < 0.001). Calcinosis resolved partially or completely in 3/6 patients, while the single ILD case showed no change. IVIG was well tolerated, with only mild adverse effects. IVIG is a safe and effective treatment for JDM, particularly in patients with refractory or skin-predominant disease. Given the retrospective nature of the study and absence of a control group, causal inferences should be made with caution; however, our findings support IVIG as a valuable option in real-life management. These findings support the use of IVIG as part of an individualized treatment approach; however, further prospective, controlled studies are needed to optimize its role in long-term disease management.