An international team has developed and validated the first global classification criteria for pediatric chronic nonbacterial osteomyelitis (CNO), offering a standardized tool to improve research on the rare disease.
CNO, an autoinflammatory bone disease with no known cause, has an estimated global incidence of 0.4 to 2.3 cases per 100,000 children and adolescents annually, according to a paper describing the guidelines and the process of devising them.1 CNO causes bone inflammation, leading to pain and swelling, plus such potential long-term complications as deformity or disability. Diagnosing the disorder is difficult because of its gradual onset and varying symptoms, which often overlap with other conditions.
The CNO classification criteria resulted from an effort jointly supported by the ACR and EULAR. Involvement and testing by a global group of researchers allows generalization of results beyond a single center or country, says the criteria’s first author, Yongdong Zhao, MD, PhD, director of the CNO clinical program at Seattle Children’s Hospital.
The criteria are intended primarily to improve research on the condition and will be used in future clinical drug trials for CNO, Dr. Zhao adds. He points out that clinicians and patients have no medication approved by the U.S. Food & Drug Administration for the condition, while the estimated number of newly diagnosed CNO patients worldwide has increased from 8 per million children to 23 per million each year.1
Dr. Seza Ozen
The criteria development process “raised awareness for this disease on both sides of the Atlantic,” says criteria senior author Seza Ozen, MD, MSc, head of the Department of Pediatric Rheumatology at Hacettepe University, Ankara, Turkey, and president of the Pediatric Rheumatology European Society (https://www.pres.eu). “I’m sure this classification system is going to help in the future studies.”
The Criteria
The criteria were developed in four phases by researchers from a dozen countries in North and South America, Europe, Australia and New Zealand. The phases involved generating candidate criteria items, reducing and defining those items, weighting criteria and identifying a threshold for CNO classification, and refinement and validation.
First, pediatric rheumatologists identified relevant disease features via surveys. The researchers refined and weighted the identified features in a structured decision-making process. The researchers then tested the criteria in a development cohort of 441 patients and validated them in a separate cohort of 514 children worldwide. They found the new criteria had a sensitivity of 82% and specificity of 98% in the validation cohort.
