Working Diagnosis:
Chronic nonbacterial osteomyelitis (CNO)

Treatment:
He was initially treated with naproxen twice daily per Rheumatology recommendations. At his initial outpatient Rheumatology follow-up visit after hospital discharge, he reported daily bilateral knee pain without swelling.

Additional treatment options were discussed, including corticosteroids, methotrexate, tumor necrosis factor inhibitors, and bisphosphonates. However, the patient's parents elected to continue treatment with naproxen.

Outcome:
The patient's erythrocyte sedimentation rate decreased to 16 mm/hour following initiation of treatment. He was subsequently lost to follow-up.

Author's Comments:
Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder that most commonly presents in pediatric patients. The underlying pathophysiology is thought to involve dysregulation of the innate immune system, including abnormal cytokine expression and inflammasome activation, with potential genetic contributions.1-2

Patients most commonly present with bone pain, although localized swelling and, less frequently, systemic symptoms may also occur. While lesions involving the clavicle and mandible are highly suggestive of CNO, other commonly affected sites include the metaphyses of long bones, vertebral bodies, and pelvis. Disease may present as either a unifocal or multifocal process.1-2

Chronic nonbacterial osteomyelitis remains a diagnosis of exclusion. The American College of Rheumatology and the European Alliance of Associations for Rheumatology recently published updated classification criteria for pediatric chronic nonbacterial osteomyelitis, providing a structured diagnostic framework for patients with suspected disease.3

Magnetic resonance imaging remains the imaging modality of choice because of its ability to identify both symptomatic and clinically silent lesions. Nonsteroidal anti-inflammatory drugs are considered first-line treatment; however, remission rates with monotherapy are relatively low. Additional treatment options may include corticosteroids, disease-modifying antirheumatic drugs, tumor necrosis factor inhibitors, and bisphosphonates in refractory cases.1-2

Although CNO is often self-limited, recurrent disease is common. With respect to return to sport, the goal is full participation once symptoms have improved and the athlete can participate without pain, limping, or altered biomechanics.

Editor's Comments:
Chronic nonbacterial osteomyelitis is a rare autoinflammatory bone disorder, with an estimated incidence of approximately 4 cases per million children annually. It most commonly presents between 7 and 9 years of age and occurs more frequently in females, with an approximate 2:1 female-to-male ratio.1-2 Because symptoms are often mild and nonspecific, diagnosis may be delayed for years. For this reason, CNO should remain within the differential diagnosis for children and adolescents presenting with persistent atraumatic bone pain.1-2

Whole-body magnetic resonance imaging is considered the imaging modality of choice because it can identify both symptomatic and clinically silent lesions. Chronic nonbacterial osteomyelitis remains a diagnosis of exclusion and requires evaluation for alternative etiologies, including infection, malignancy, and other inflammatory disorders. Most patients demonstrate multifocal disease involving two or more skeletal sites. Radiographs may demonstrate sclerosis, lytic lesions, or hyperostosis.1-2

Although the exact pathophysiology remains incompletely understood, current evidence suggests dysregulated cytokine expression and abnormal inflammasome activation contribute to disease development.1-2 Nonsteroidal anti-inflammatory drugs are considered first-line therapy, while corticosteroids, cytokine-targeted therapies, and bisphosphonates may be utilized in refractory cases.1-2

References:
1. Zhao DY, McCann L, Hahn G, Hedrich CM. Chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO). Journal of Translational Autoimmunity. 2021;4:100095. doi:10.1016/j.jtauto.2021.100095.

2. Lim L, Laxer RM. Chronic nonbacterial osteomyelitis: A noninfectious autoinflammatory disorder of bone. The Journal of Pediatrics. 2025;283:114636. doi:10.1016/j.jpeds.2025.114636.

3. Zhao Y, Oliver MS, Schnabel A, et al. EULAR/American College of Rheumatology Classification Criteria for Pediatric Chronic Nonbacterial Osteomyelitis. Arthritis Rheumatol. 2026;78:537-547.

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