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Objective.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. The American College of Rheumatology (ACR) 1997, Systemic Lupus International Collaborating Clinics (SLICC) 2012, and European League Against Rheumatism (EULAR)/ACR 2019 SLE classification criteria are formed based on data mainly from adult patients. We aimed to test the performances of the SLE classification criteria among pediatric patients with SLE.Methods.Pediatric patients with SLE (n = 262; 80.9% female) were included from 3 different centers in Turkey. As controls, 174 children (60.9% female) with other diseases who had ANA (antinuclear antibody) test results were included. The gold standard for SLE diagnosis was expert opinion.Results.The sensitivities of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 criteria were 68.7%, 95.4%, and 91.6%, respectively. The specificities of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 criteria were 94.8%, 89.7%, and 88.5%, respectively. Eighteen patients with SLE met the SLICC 2012 but not the EULAR/ACR 2019 criteria. Among these, hematologic involvement was prominent (n = 13; 72.2%). Eight patients with SLE fulfilled the EULAR/ACR 2019 but not the SLICC 2012 criteria. Among these, joint involvement was prominent (n = 6; 75%).Conclusion.To our knowledge, this is the largest cohort study of pediatric SLE to test the performances of all 3 classification criteria. The SLICC 2012 criteria yielded the best sensitivity, whereas the ACR 1997 criteria had the best specificity. SLICC 2012 criteria performed better than EULAR/ACR 2019 criteria. Separation of different hematological manifestations in the SLICC 2012 criteria might have contributed to the higher performance of this criteria set.

Periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome is a periodic fever syndrome of childhood with an unknown etiology. Our aim was to compare the features between PFAPA syndrome patients from Turkey and those from the US, and patients with and without MEFVvariants, and to test the performance of the Eurofever criteria in excluding other autoinflammatory disorders. Seventy‐one children with PFAPA syndrome, followed in Hacettepe University, in Ankara, Turkey, and 60 patients at Boston Children's Hospital in the US were enrolled. MEFVgene‐variant analysis was performed in 56 patients with Sanger sequencing. In patients from Turkey, symptom onset was at a younger age, fever attacks were of shorter duration, and pharyngitis was more frequent, whereas adenitis, headache, and nausea/vomiting were less frequent during attacks, when compared to patients from the US (P< 0.05). More patients from the Turkish cohort were classified in the familial Mediterranean fever (FMF) group according to the Eurofever criteria than patients from the US (66.2% versus 10%; P< 0.001). Two patients were diagnosed with FMF after MEFVanalysis. Twenty‐one patients (37.5%) had a single MEFVvariant. No significant differences in phenotype were found between patients with and without MEFVvariants. The differences between patients from the Turkish and US cohorts may be due to epigenetic or environmental factors. In addition, the Eurofever FMF criteria may perform better in certain areas, if the weight of ethnic origin parameter or cutoff values were modified.

Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-κB regulatory protein A20, in six unrelated families with early-onset systemic inflammation. The disorder resembles Behçet's disease, which is typically considered a polygenic disorder with onset in early adulthood. A20 is a potent inhibitor of the NF-κB signaling pathway. Mutant, truncated A20 proteins are likely to act through haploinsufficiency because they do not exert a dominant-negative effect in overexpression experiments. Patient-derived cells show increased degradation of IκBα and nuclear translocation of the NF-κB p65 subunit together with increased expression of NF-κB–mediated proinflammatory cytokines. A20 restricts NF-κB signals via its deubiquitinase activity. In cells expressing mutant A20 protein, there is defective removal of Lys63-linked ubiquitin from TRAF6, NEMO and RIP1 after stimulation with tumor necrosis factor (TNF). NF-κB–dependent proinflammatory cytokines are potential therapeutic targets for the patients with this disease.