To be classified as having CNO, a child must be younger than 18 years old and have bone pain or musculoskeletal limitations for at least six weeks, the final criteria say. Imaging must show abnormal bone findings, such as inflammation visible on radiography or magnetic resonance imaging (MRI). Additionally, the classification process involves excluding mimicker conditions including malignancies, infections, vitamin C deficiency and the genetic disorder hypophosphatasia.
Using the criteria involves evaluating clinical findings and laboratory and pathology findings in 10 domains and assigning points to them. The clinical domains include bone lesion sites, bone lesion patterns, patient age at disease onset, coexisting conditions and fever. Laboratory and pathology domains include anemia, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR) and bone biopsy findings, although the criteria can be applied without a bone biopsy. A minimum of 55 points is required to meet the classification threshold.
The paper and Dr. Zhao describe the domains included in the point system:
- Symptom onset before age 18—The non-genetic form of CNO is rare in children younger than 3, so clinicians and researchers must exercise extreme caution when classifying a patient younger than 3 years old.
- Bone lesion pattern and sites—The mandible and clavicle get the most points because these sites are more common in CNO than in mimicker conditions. Sites other than clavicle, mandible, skull or hand get fewer points. Affected bones, such as the femur and tibia, are equally affected in mimicker conditions and do not carry extra weight toward CNO classification.
- Distribution of bone lesions based on imaging—Multifocal lesions get the most points because previous research shows most patients with CNO have multiple lesions at diagnosis or eventually develop them. Symmetrical lesion patterns draw points because they are more common in CNO than in mimicker conditions.
- Coexisting conditions prior to CNO diagnosis—Inflammatory bowel disease and specific skin diseases, such as psoriasis and pustulosis, are highly associated with CNO and draw the most points. Axial arthritis, which primarily affects the spine and sacroiliac joints, gets fewer points if it does not involve skin symptoms.
- Anemia—The study showed a significant difference between the distribution of patients with CNO and mimicker conditions, and hemoglobin under 10 g/dL.
- Fever—Fever is more associated with infectious osteomyelitis and malignancy, but may occur in 10–20% of patients with CNO. Therefore, fever at presentation is less favorable toward classification of CNO and receives no points.
- ESR below 60—ESR of 60 mm/h or less is associated more with infectious osteomyelitis and malignancy and receives no points. ESR above this threshold garners points.
- CRP—A CRP of 30 mg/L or greater is more associated with infectious osteomyelitis and malignancy, so it does not get any points. A CRP below that threshold gets points. However, A CRP of 30 mg/L or greater can also be present in 10–20% of patients with CNO.
Biopsy
Although the criteria do not require bone biopsy, the criteria do include it in scoring. Dr. Zhao explains that inflammation within bones refers to the presence of immune cells, such as neutrophils, lymphocytes and plasma cells. The latter two are more commonly seen in bone biopsy in CNO. In the study, fibrosis indicated subacute and chronic repairing process. Neither is specific for CNO, but chronic inflammation and fibrosis are more common in CNO than in mimicker conditions, according to Dr. Zhao.
