Abstract
Chronic non-bacterial osteomyelitis (CNO) is caused by aseptic inflammation of bones, primarily driven by the innate immune system. CNO may display different clinical presentations (acute vs chronic, uni- vs multifocal) and is accompanied by other inflammatory disorders in up to a third of patients. Once considered a rare disorder, it has become clear that many patients were underdiagnosed. With increasing awareness and the development of total-body MRI protocols, CNO recognition and diagnosis have greatly improved. Our knowledge of the clinical manifestations and outcomes of CNO has been refined in recent years, especially thanks to the recruitment of large international series. Similarly, new insights into the pathogenesis have been gained by the development of mice models and identification of rare monogenic diseases that resemble CNO. Unfortunately, these advances have not been paralleled in the therapeutic management. In the absence of prospective controlled trials, therapeutic strategies still rely on low-level evidence studies. About half of the patients respond to first-line therapies, but a more refractory and/or chronic disease course requires additional treatments. This narrative review aims to provide the practicing physician with an update on CNO pathogenesis, clinical presentation, associated inflammatory conditions, and diagnostic investigations, and includes a concise summary of current therapeutic recommendations. CONCLUSION: While major progresses have been made in the recognition and management of CNO, significant challenges remain, in particular regarding the treatment of refractory patients, and those with associated inflammatory disorders. WHAT IS KNOWN: • Many physicians caring for children will encounter patients suffering of (suspected) CNO. CNO diagnosis requires exclusion of numerous conditions included in the differential diagnosis, which may be challenging. WHAT IS NEW: • We provide an updated review of recent findings in the field CNO, including imaging and diagnostic strategies, associated inflammatory diseases and long-term outcomes data. • We focus particularly on the challenges encountered by clinicians in the diagnosis and treatment of these patients. • We highlight knowledge gaps in the understanding and treatment of CNO, that should stimulate future research.