Chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO)

Abstract

Chronic nonbacterial osteomyelitis (CNO) is an inflammatory bone disorder that most frequently affects children and adolescents. Chronic recurrent multifocal osteomyelitis (CRMO) is a severe form of CNO, usually characterized by symmetrical inflammatory bone lesions and its waxing and waning character. Sometimes severe and chronic pain can significantly affect the quality of life and psychosocial development of individuals affected. In the absence of prospectively tested and widely accepted diagnostic criteria or disease biomarkers, CNO remains a diagnosis of exclusion, and infections, malignancy and other differentials require consideration (1). The pathophysiology of CNO is not fully understood, but imbalanced cytokine expression and increased inflammasome activation in monocytes from CNO patients contribute to a pro-inflammatory phenotype that contributes to bone inflammation (2). Currently, no medications are licensed for the use in CNO. Most patients show at least some response to nonsteroidal anti-inflammatory drugs, others require more aggressive treatment that can include corticosteroids, cytokine-blocking agents and/or bisphosphonates (3). While under the care of an experienced team and sufficient treatment, the prognosis is good, but some patients will develop sequalae which can include vertebral compression fractures (1).

Keywords: CNO; CRMO; Chronic nonbacterial osteomyelitis; Chronic recurrent multifocal osteomyelitis; Pathophysiology; Treatment.

Fig. 1

Typical bone involvement in CNO. A-C) MRI images from a 13-year-old girl with CNO and Crohn’s disease showing hyperintense signal alterations in a thickened left mandible with bone destruction (TIRM: A, B), and contrast enhancement (T1 with fat saturation, C). D) Conventional X-ray showing a clavicular CNO lesion with bone thickening and periostal reaction. E) MRI (TIRM) showing hyperintense signal alterations in a thickened and destroyed left clavicle of a 15-year-old CNO patient. F) MRI (TIRM) showing hyperintense lesions in multiple vertebral bodies of a 13-year-old CNO patient.

Fig. 2

Suggested imaging approach in CNO at diagnosis. A) regional X-ray showing minimal sclerosis of the right ilium, B) MRI (TIRM sequences) showing hyperintense signal in os ilium and proximal femur with reaction of surrounding tissue, C) MRI (T1 with contrast) showing contrast enhancement of thickened os ilium with bone destruction and perifocal soft tissue reaction D) MRI (diffusion weighted images; DWI) showing restricted diffusion in os ilium and proximal femur, E) Whole-body MRI showing multifocal skeletal hyperintense lesions (TIRM).

Fig. 3

Whole-body MRI scans of patients with differential diagnoses to CNO (coronal TIRM sequences). A) Skeletal metastases of neuroblastoma with multiple small and large areas of hyperintense signal alterations (arrows). B) Mycobacteriosis in interferon gamma receptor (IFNGR) defect with small hyperintense areas and central hypointensity (arrow). C) Primary bone lymphoma with inhomogenous hyperintense lesions of the entire skeleton. D) Langerhans cell histiocytosis with hyperintense lesions in proximal femur, right os ilium and third right rib (arrows). E) Polyostotic fibrous dysplasia with inhomogenous hyperintense tibiae and femora (arrows).