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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: With advances in genetic testing, monogenic lupus is increasingly recognized, yet disease-specific classification criteria are lacking. We compared all three classification criteria sets in the same monogenic lupus cohort and, for the first time, evaluated their performance across distinct genetic pathways. Methods: This national multicentre study included 88 genetically confirmed monogenic lupus patients from 22 paediatric rheumatology centres across Türkiye. Fulfilment of the AmericanCollege of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012 and European League Against Rheumatism (EULAR)/ACR-2019 criteria and pathway-based differences in classification performance were assessed. Results: Overall, 74% (n = 65) fulfilled ACR-1997, 70.5% (n = 62) SLICC-2012 and EULAR/ACR-2019 criteria, and 62.5% (n = 55) met all three, whereas 17% (n = 15) met none. Agreement was substantial (κ = 0.63–0.73), with no significant differences between criteria (P > 0.05). Classification performance differed significantly across genetic pathways (P < 0.05), with the highest fulfilment performances in complement deficiencies and the lowest in nucleic acid metabolism and type I interferon pathway defects. Most patients who did not fulfil any classification criteria had nucleic acid metabolism and clearance defects (13/15, 86.7%). Domain-level analyses showed that classification success was mainly driven by mucocutaneous, immunologic and renal domains. Complement and immune-regulation defects showed a more classical lupus phenotype, with most fulfilling all three criteria (78.6%, 22/28 and 77.8%, 14/18), whereas the proportion was lower in type I interferon pathway and nucleic acid metabolism and clearance defects (33.3%, 2/6 and 47.2%, 17/36). No classification criteria were superior within genetic pathways. Conclusion: One-third of genetically confirmed monogenic lupus patients remained unclassified, particularly those with interferon-related and nucleic acid metabolism defects, highlighting pathway-dependent limitations of current classification criteria.

Colchicine preparation switching is recommended before interleukin-1 (IL-1) inhibitor therapy in pediatric patients with colchicine-resistant familial Mediterranean fever (crFMF); however, real-world outcomes after switching are not well characterized. We aimed to evaluate the effectiveness of colchicine preparation switching and to compare clinical outcomes between patients managed with switching alone and those who subsequently required IL-1 inhibitor therapy. This retrospective inception cohort study included 103 pediatric crFMF patients carrying biallelic pathogenic MEFV exon 10 variants who underwent a switch from coated to compressed colchicine between August 2016 and May 2025. Clinical, laboratory, and genetic data were collected. Disease activity was assessed using the Pras score, the International Severity Scoring System for familial Mediterranean fever, and the Mor score. Patients were classified according to IL-1 inhibitor requirement; treatment escalation was the primary endpoint. Following colchicine preparation switching, attack frequency and disease activity scores decreased significantly (all p < 0.001). Sixty-three patients (61.2%) showed significant reductions in all major attack manifestations, whereas among 40 patients (38.8%) requiring IL-1 inhibitors, only fever decreased significantly (p = 0.012). Conclusion: Colchicine preparation switching significantly reduced attack frequency and disease activity in children with crFMF and may represent an effective intermediate therapeutic strategy before escalation to IL-1 inhibitor therapy. What is Known: • Colchicine preparation switching is recommended before IL-1 inhibitor therapy in colchicine-resistant familial Mediterranean fever (crFMF), but evidence supporting this approach in children is limited. • Previous studies have reported improved disease control after switching colchicine preparations. What is New: • This study provides long-term pediatric data on the clinical course after colchicine preparation switching, including subsequent escalation to IL-1 inhibitor therapy. • Patients requiring subsequent IL-1 inhibitor therapy developed earlier subclinical inflammation and showed a less complete clinical response after switching.

1. Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease in children and is caused by mutations in the MEFV gene, leading to dysregulation of the pyrin inflammaso...

The purpose of the study is to evaluate the demographic characteristics, clinical features, and management strategies of TNF inhibitor-related autoimmune d

Objective: This study aimed to describe the diagnostic spectrum, management strategies, and outcomes of critically ill children co-managed by rheumatology and the pediatric intensive care unit (PICU). Methods: A retrospective cohort study was conducted at a tertiary referral hospital PICU with integrated pediatric rheumatology collaboration between August 2016 and January 2025. Patients were categorized into 2 groups: Group 1 comprised children with a previously established rheumatologic diagnosis prior to PICU admission (n=20), and Group 2 comprised children without a known rheumatologic diagnosis at PICU admission who were either newly diagnosed during the PICU stay or required pediatric rheumatology involvement for hyperin-flammatory conditions (n=67). Patients who neither received a rheumatologic diagnosis norrequired pediatric rheumatology involvement during PICU admission were excluded. Data on demographic characteristics, diagnoses, treatments, and mortality were analyzed. Results: In Group 1, vasculitis (35%), systemic lupus erythematosus (SLE, 25%), and systemic juvenile idiopathic arthritis (30%) predominated; most were admitted with disease flare. Mortality was highest in SLE (60% in Group 1, 43% overall). In Group 2, secondary hemophagocytic lymphohistiocytosis (HLH) was the most common diagnosis (n=56). Mortality reached 28.3% in secondary HLH. Non-survivors more frequently required mechanical ventilation within the first 24 hours of PICU admission. Median PICU stay ranged from 5 days in vasculitis to 13 days in SLE. Conclusion: Critically ill children co-managed by rheumatology and intensive care teams most often present with hyperinflammatory syndromes. Early rheumatology involvement and multidisciplinary care appear essential for optimal patient outcomes.

Background. Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory disease. Chronic nonbacterial osteomyelitis (CNO) represents another autoinflammatory disorder characterized by sterile bone inflammation. Although musculoskeletal pain is common in MKD, CNO-like bone lesions have rarely been described. Tocilizumab has been used separately in MKD / hyper-IgD syndrome (HIDS) and in CNO; however, pediatric cases showing both conditions together and responding completely to IL-6 blockade have not been previously reported. Case Presentation. We present a 16-year-old boy born to consanguineous parents who experienced early-onset recurrent fever episodes with abdominal pain, maculopapular rash, oral ulcers, and conjunctival injection. He was initially misdiagnosed with FMF and IgA vasculitis and treated with colchicine with partial improvement. Persistent systemic inflammation prompted referral to our tertiary center at age 9. A periodic fever gene panel revealed a homozygous MVK p.V377I mutation, confirming MKD. Anakinra therapy was initiated. Although no attacks occurred during the first month, flares characterized by fever, abdominal pain, rash, and elevated acute-phase reactants recurred in the second and third months, reflecting a partial response. Consequently, treatment was switched to canakinumab. Toward the end of the second year of IL-1 blockade, attack frequency increased to once every three months, and at age 12 he developed diffuse musculoskeletal pain. Whole-body magnetic resonance imaging demonstrated multifocal metaphyseal bone marrow edema compatible with CNO-like lesions. Sulfasalazine was added but discontinued after drug-induced pancreatitis. Given persistent systemic inflammation and inadequate response to IL-1 inhibitors, canakinumab was replaced with weekly subcutaneous tocilizumab, resulting in rapid improvement in bone pain and systemic inflammation. Since the third month of tocilizumab therapy, he has remained clinically stable with normalized inflammatory markers and only a single mild flare over the last year. Conclusion. This case highlights the potential role of IL-6 inhibition in complicated MKD presenting with autoinflammatory bone disease refractory to standard therapies.

Background: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder with heterogeneous presentations, and no disease-specific biomarker exists, making diagnosis challenging. Recently, the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) proposed new classification criteria; however, their performance relative to the established Bristol criteria has not been systematically validated. Methods: We conducted a retrospective, multicenter cohort study across 10 pediatric rheumatology centers, including 114 children with CNO and 116 controls with mimicking conditions. Demographic, clinical, laboratory, imaging, and biopsy data were systematically collected. Each participant was assessed according to both the EULAR/ACR classification and the Bristol diagnostic criteria. Sensitivity, specificity, predictive values, likelihood ratios, receiver operating characteristic (ROC) analysis, and agreement statistics were calculated using expert clinical diagnosis as the reference standard. Results: The EULAR/ACR criteria demonstrated 97.4% sensitivity and 81.0% specificity, compared with 79.8% and 80.2% for the Bristol criteria. The negative likelihood ratio was markedly lower for the EULAR/ACR criteria (0.03 vs. 0.25), underscoring their strong rule-out capacity. Concordance between systems was substantial ( κ =0.66). Discordant cases showed that the EULAR/ACR criteria better identified atypical phenotypes such as unifocal or nonclavicular disease. Elevated ESR supported the diagnosis of CNO, whereas profound anemia was almost exclusive to mimicking disorders. Conclusion: The EULAR/ACR criteria provide a more sensitive and inclusive framework for CNO while maintaining robust specificity. Their ability to capture atypical cases may reduce diagnostic delay and unnecessary biopsies, though clinical judgment remains essential in distinguishing CNO from overlapping inflammatory arthritis. Clinical Relevance: Validation of the EULAR/ACR classification criteria may facilitate earlier and more accurate classification of pediatric CNO and reduce unnecessary invasive diagnostic procedures.

To evaluate the clinical characteristics, and treatment patterns of difficult-to-treat (D2T) disease in children with polyarticular juvenile idiopathic arthritis (pJIA) treated with biologic disease-modifying antirheumatic drugs (bDMARDs). This single-center, cross-sectional study included children with RF-positive or RF-negative pJIA who received bDMARD. D2T defined according to EULAR criteria, as inadequate response to at least two bDMARDs with different mechanisms of action. Disease activity was assessed using the JADAS-27. Treatment patterns, switches, and factors associated with D2T were analyzed. A total of 59 pJIA patients (79.9% female) were included, with a median follow-up of 60 months. Ten patients (16.9%) fulfilled the criteria for D2T disease after a follow-up duration of 36 months. At diagnosis, D2T patients had significantly higher inflammatory markers than non-D2T patients, with higher median CRP (45 vs. 12 mg/L, p = 0.002) and ESR (77 vs. 38 mm/h, p = 0.003) values. In univariate analyses, higher CRP, ESR, temporomandibular joint involvement, and higher JADAS-27 at bDMARD initiation were associated with D2T status (p < 0.05). D2T course was associated with temporomandibular joint involvement, elevated inflammatory markers, and higher disease activity at the initiation of the first biologic therapy.