Zhao Y, Oliver MS, Schnabel A, Wu EY, Wang Z , et al.
Annals of the rheumatic diseases •
To develop and validate classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO) jointly supported by the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR). This international initiative had 4 phases: (1) candidate items were proposed in a survey of paediatric rheumatologists, (2) criteria definition and reduction by Delphi and nominal group technique exercises, (3) criteria weighting using multicriteria decision analysis, and (4) refinement of weights and threshold score in a development cohort of 441 patients and validation in another cohort of 514 patients. The new EULAR/ACR classification criteria for CNO require typical radiographic or magnetic resonance imaging findings and bone pain as an obligatory entry criterion and exclusion criteria of malignancy, infection, vitamin C deficiency, and hypophosphatasia, followed by additive weighted criteria in 5 clinical (site of bone lesions, pattern of bone lesions, age at onset, coexisting conditions, fever) and 4 pathology/laboratory domains (bone biopsy findings if done, anaemia, C-reactive protein level, and erythrocyte sedimentation rate). A total score ≥55 is required for classification as CNO. The new criteria had a sensitivity of 82% and specificity of 98% in the validation cohort. These new classification criteria for paediatric CNO developed with international input reflect current views about CNO, have high specificity and good sensitivity, and provide a key foundation for future CNO research.
Tucker LB, Niemietz I, Mangat P, Belen M, Tekano J , et al.
Clinical and experimental rheumatology •
To evaluate the ethnic diversity of children with a systemic autoinflammatory disease (SAID) in a multi-ethnic Canadian province. Self-reported ethnicity of 149 children and adolescents with a SAID in British Columbia, Canada, was analysed for ethnic representation among individual patients, across the cohort, within particular SAIDs, and compared to provincial census data on ethnic diversity. Half of reported cases had a diagnosis of either PFAPA (23.5%) or an unclassifiable autoinflammatory syndrome (31.5%), with a monogenic SAID diagnosed in only 12.8% of cases. The majority of participants (73.1%) were mixed ethnicity with European and Asian heritage reported most frequently (57.0% and 23.0% of all responses, respectively). Ethnic diversity reflected regional diversity except for West Asian, Arabic, Jewish, and Eastern European heritage, which were over-represented in SAID patients, and Chinese descent, which was under-represented in our cohort compared to the general population of British Columbia. Results from this study show extensive multi-ethnic diversity in individual patients and across the various SAIDs inclusive of monogenic SAIDs that are frequently associated with particular ethnicities. Although not disproportionately represented, this is the first report of systemic autoinflammatory disease in Canadian children of Indigenous heritage.
Sundqvist M, Wekell P, Osla V, Bylund J, Christenson K , et al.
Arthritis and rheumatism •
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease of unknown etiology that primarily affects preschool-aged children. PFAPA syndrome is characterized by recurrent attacks of fever and symptoms of inflammation consistent with the disease acronym. Since autoinflammatory diseases are, by definition, mediated by cells of the innate immune system, the aim of this study was to evaluate the functional features of neutrophils, the most abundant innate immune cell in the circulation, in children with PFAPA syndrome. Blood polymorphonuclear leukocytes (PMNs), obtained from patients with PFAPA syndrome during both febrile and asymptomatic, afebrile phases of the disease, as well as from healthy children (afebrile controls) and children with fever and abdominal pain (febrile controls), were analyzed for 3 key neutrophil characteristics: 1) apoptosis (measured by annexin V/7-aminoactinomycin D staining), 2) production of reactive oxygen species (ROS) (measured by luminol/isoluminol-amplified chemiluminescence), and 3) priming status (measured as responsiveness to galectin-3 and up-regulation of CD11b). Compared to PMNs obtained from patients with PFAPA syndrome during an afebrile interval and those from febrile controls, PMNs obtained from patients during a PFAPA syndrome flare produced elevated levels of intracellular NADPH oxidase-derived ROS, had significantly diminished rates of spontaneous apoptosis, and displayed signatures of priming. In contrast, PMNs from afebrile patients with PFAPA syndrome had a significantly elevated rate of spontaneous apoptosis compared to PMNs from afebrile controls. These findings demonstrate that 3 key aspects of neutrophil innate immune function, namely, apoptosis, priming, and generation of an intracellular oxidative burst, are altered, most prominently during febrile attacks, in children with PFAPA syndrome.
