The quiet flame: whole-body MRI and the underestimated burden of pediatric chronic non-bacterial osteomyelitis (CNO)

To characterize the radiologic spectrum, lesion distribution, and diagnostic features of Chronic non-bacterial osteomyelitis (CNO) in pediatric patients, including key imaging mimics, and to determine whether clinical presentation correlates with imaging disease burden. Retrospective study included patients younger than 21 years diagnosed with CNO between 2014 and 2024. Clinical presentation, lesion distribution, MRI and radiographic findings, and biopsy results were reviewed. Imaging mimics-including infection, malignancy, and trauma-were evaluated for differential diagnosis. Thirty-two pediatric patients met inclusion criteria (median age 10 years; 62% female). A total of 144 MRI lesions were identified (median 4.5 per patient, range 1-11). Most commonly involved bones were the femur (65.6%), tibia (56.3%), sacrum (31.3%), clavicle (37.5%), and ilium (18.8%). Clinical presentation did not correlate with imaging disease burden: median MRI lesion counts were similar across clinical symptoms (pain: 3.50 lesions; swelling: 5.50; pain and swelling: 1.50; abnormal gait and pain: 4.00; Kruskal-Wallis p = 0.627). This dissociation between clinical symptoms and lesion extent demonstrates that imaging findings cannot be predicted from clinical presentation alone. Whole-body MRI (WB-MRI) performed in 22 patients (68.8%), yielded more lesions (122 lesions, median 5.5 per patient), than regional MRI performed in 10 patients (31.3%) (22 lesions, median 2.0 per patient, p = 0.003). CONCLUSION: CNO demonstrates multifocal metaphyseal marrow edema with clavicular involvement in most of the cases, distinguishing it from mimics. The pronounced clinical-radiologic dissociation and high lesion burden found at the time of imaging emphasize the occult nature of CNO. These findings highlight the critical need for early diagnostic protocols, such as systematic baseline WB-MRI, to mitigate the substantial diagnostic delays and high lesion burden demonstrated in this cohort. WHAT IS KNOWN: • Chronic non-bacterial osteomyelitis (CNO) is a rare pediatric autoinflammatory bone disorder characterized by recurrent, sterile multifocal lesions predominantly aff ecting the metaphyses of long bones, with clinical features that frequently overlap with infection and malignancy. WHAT IS NEW: • Whole-body MRI (WB-MRI) detects significantly more lesions per patient than regional MRI, revealing a pronounced dissociation where initial clinical symptoms fail to predict the true extent of occult skeletal disease burden. • A 10-year institutional review demonstrates that substantial subclinical lesion burdens accumulate during prolonged diagnostic delays, emphasizing the critical need for early, systematic baseline WB-MRI.