Chronic non-bacterial osteomyelitis presenting as fever of unknown origin in a child: a diagnostic pitfall

Background : Chronic non-bacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder in children and adolescents. Bone pain is the most common presenting symptom, it rarely manifests as prolonged recurrent fever of unknown origin, which may lead to extensive diagnostic evaluations, including invasive procedures. Case presentation: We report a 12-year-old girl who presented with recurrent fever as the predominant symptom, accompanied by delayed and intermittent joint pain. Extensive infectious, rheumatologic, and oncologic investigations—including repeated cultures, metagenomic next-generation sequencing, and bone marrow examination—were unrevealing. Magnetic resonance imaging and positron emission tomography–computed tomography demonstrated multifocal hypermetabolic bone marrow lesions, raising concern for malignancy. Histopathological examination of a femoral bone biopsy revealed lymphoplasmacytic infiltration with focal fibrosis and no evidence of infection or malignancy, leading to a diagnosis of CNO. Conclusion : This case illustrates an uncommon presentation of pediatric CNO characterized by fever of unknown origin and multifocal bone lesions. CNO should be considered in the differential diagnosis of children with persistent fever after exclusion of infectious and malignant causes to avoid diagnostic delay and unnecessary interventions.