Chronic nonbacterial osteomyelitis (CNO) is a chronic autoinflammatory bone disease that typically affects children. It can cause complications such as bone deformities and vertebral fractures. Previous studies were retrospective in nature. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) CNO workgroup has created a consensus treatment plan for children with CNO refractory to NSAIDs and/or having spinal lesions. In order to determine the relative effectiveness of commonly used second-line medications, a longitudinal prospective study is needed. This study was approved by the Seattle Children’s Institutional Review Board (#1232). The CHronic nonbacterial Osteomyelitis International Registry (CHOIR) enrolls subjects under 21 years of age with a diagnosis of CNO, refractory to NSAID and/or having spinal lesions. The goal is to enroll 2000 patients and follow for at least 5 years. Demographic, clinical, laboratory, imaging data as well as patient/parent-reported outcomes were collected at baseline and follow up visits. 136 subjects were enrolled across 8 centers between June 2018 and January 2020, with 40 more centers anticipated to join. Data entry and data analysis are ongoing. We are presenting an inception cohort of over one hundred subjects. We expect that the longitudinal data will allow us to distinguish the responses from patients to different second-line medications. The patient/parent-reported outcomes are also expected to be an important component of the overall assessment. This is the first ever prospective longitudinal multicenter study on children with CNO. Results are expected to be highly applicable to improve clinical care.

Chronic Nonbacterial Osteomyelitis (CNO) is a severe and occult autoinflammatory bone disease of unknown cause. CNO predominantly affects children and young adults, with older literature reporting estimated annual incidence rates of 0.4 per 100,000 children. A timely diagnosis is challenging, but critical, because CNO may result in permanent bone damage, long-term disability, and disfigurement when left untreated. Diagnostic criteria were proposed by three groups. These sets of criteria were derived from single-center cohorts and none has been validated. In the proposed initiative, we developed a consensus among internationally recognized experts based on the analysis of a large international cohort of pediatric CNO patients and pediatric disease controls in order to develop and validate classification criteria for pediatric CNO. IRB approval was obtained at each site. CNO cases and mimicker cases were identified. Data were collected retrospectively using uniform case report form. The demographic, symptoms, physical examination, lab result and imaging feature were obtained. Descriptive statistics were performed. Our international group have collected a total of 360 cases including 226 CNO and 134 mimicker cases from 18 centers in 4 continents. 53% of subjects were females and 69% were whites. The typical site of bone pain is the lower extremity (231, 65%) followed by the lower torso (83, 24%). The most frequent imaging technique performed is the MRI (326, 91%). The top three mimicker diseases were infectious osteomyelitis (35, 10%), primary malignant bone disease (27, 8%) and juvenile idiopathic arthritis (24, 7%). The diagnosis of CNO was most commonly based on imaging features (116, 55%) and bone biopsies (61, 29%). A large international case repository was successfully created by using predetermined data collection form. These datasets can aid the development of classification criteria and future validation.

Chronic Non-bacterial Osteomyelitis (CNO), also known as Chronic Recurrent Multifocal Osteomyelitis (CRMO), is an auto inflammatory bone condition that causes persistent bone pain, poor growth, and complications such as vertebral compression fracture. Understanding the possible epidemiological risk factors impacting the disease will provide all physicians including pediatric rheumatologists a better comprehension of the disease when diagnosing and treating CNO. The objectives of this study are to: 1) determine the annual incidence rate of CNO from King County; 2) compare the time to diagnosis from 2000-2019.Subjects were identified by the patient list maintained within Division of Rheumatology, Seattle Children’s Hospital. Diagnosis will be ascertained by chart review upon IRB approval based on published diagnostic criteria. Demographic and basic clinical information including the date of disease onset and physician diagnosis, first visit to a rheumatologist, and geographic location will be extracted. Public census data from King County will be used to calculate the annual incidence rate of CNO. Descriptive statistics will be performed and a nonparametric test will be used to determine the difference of time to diagnosis over time. A geographic mapping across WWAMI region for all cases will be generated to identify any patterns of case clustering. 250 subjects were identified with diagnosis of CNO between 2000 and 2019. Chart extraction will be completed after IRB approval. I expect the annual incidence rate calculated based on recent years (2015-2019) will be similar or greater than previously reported. I expect that the time to diagnosis is shortened during recent years likely due to the rise of awareness of CNO. From a large single center in the United States, I will be able to estimate the annual incidence rate of CNO in children. Continuous efforts of raising the awareness of CNO are needed to identify all cases for optimal care.