Proposed classification criteria for pediatric CNO and CRMO explained

Recently developed classification criteria for chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO) in childhood are under consideration for ACR and EULAR endorsement. During ACR Convergence 2022, members of the work group that developed the proposed criteria outlined the new criteria and the process used to define and validate them.

The Saturday, November 12, session, Development of Proposed Classification Criteria for Pediatric Chronic Nonbacterial Osteomyelitis and Chronic Recurrent Multifocal Osteomyelitis, is available for on-demand viewing for registered ACR Convergence participants through October 31, 2023, on the virtual meeting website.

“We needed expert-based and data-driven international recommendations for future collaborative studies to address geographic and ethnic differences and reflect the large spectrum of this disease we have—we know that some features change according to the geographic area—and for these criteria to have a wide dissemination, to be accepted by everyone with increased quality of care and harmonization of our approach, and to justify treatment for the health authorities and for outcome definitions,” explained Seza Ozen, MD, MSc, Head of the Department of Pediatric Rheumatology, Hacettepe University, Turkey.

Researchers analyzed more than 400 cases, including 264 CNO cases and 146 mimicker controls, from 20 centers across seven countries and four continents to develop the classification criteria. Mimicker diseases included leukemia and other cancers, infectious osteomyelitis, septic arthritis, enthesitis-related arthritis, psoriatic arthritis, and several other conditions, such as vitamin C deficiency, amplified pain syndrome, and hypophosphatasia. Case selection required follow-up a minimum of 12 months after diagnosis unless the diagnosis was confirmed by pathology.

“When you look at the characteristics of children with CNO or mimickers, you can see that the age of onset was comparable,” Dr. Ozen said. “You can see the time to diagnosis, the male-female ratio, the race, the bone biopsy rate was comparable in these data sets.”

Yongdong “Dan” Zhao, MD, PhD, RhMSUS, Associate Professor of Rheumatology, Seattle Children’s Hospital, University of Washington, outlined the 10 entry criteria identified by the workgroup and how point values for each are assigned. A pediatric patient with an aggregate score of 55 points or more out of 100 classifies as having CNO. Most criteria have three to five possible levels of points to add to the final tally.

• Specific bone sites—The highest-scoring affected sites are also the most specific sites, the mandible and clavicle. The hands and neurocranium are unlikely to be in CNO and receive no points in the absence of the most specific sites. “The most commonly affected sites, such as femur and tibia, they do not get additional weights because they are almost as commonly affected in mimickers as in CNO,” Dr. Zhao said.
• Lesion distribution pattern—Multifocal lesions, those within more than one bone, with any symmetrical pattern receive the highest point value.
• Response to antibiotics—A patient who has complete response to appropriate antibiotic monotherapy would receive no points because this response is highly suggestive of infection, Dr. Zhao explained. “If a patient had partial or no response to antibiotic monotherapy, they would receive the highest points,” he continued. Complete response is defined as the resolution of the clinical symptoms and normalization of inflammation markers.
• Bone pathology—It is important to note that not all patients undergo a bone biopsy. For those who do, a biopsy that shows no signs of inflammation or fibrosis results in no points, while a biopsy that shows signs of both results in the most possible points for this criterion.
• Age—Patients younger than 3 years old receive no points based on age because CNO diagnoses in this population are not seen. Patients 3 years or older receive full points. No further breakdown is made based on age.
• Coexisting conditions— “If a patient has multiple coexisting conditions, then you pick the one assigned the highest weight,” Dr. Zhao said. The four levels are: none of the coexisting conditions or information not available, which is assigned no points; axial arthritis present without psoriasis/palmoplantar pustulosis (PPP)/other rash or inflammatory bowel disease (IBD); psoriasis/PPP/other rash present without IBD; and presence of IBD, which results in the most points possible.
• Hemoglobin and Fever—Anemia and fever push classification against CNO. “Confirmation of the absence of these will give the highest points,” Dr. Zhao said.
• ESR and CRP—Two inflammation markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), score the lowest among the criteria because they are not specific, Dr. Zhao said. A patient with greater than 60 millimeter per hour ESR or 30 milligrams per liter CRP scores no points in these categories, while lower ESR or CRP receive the highest points.

The newly proposed criteria perform well to classify patients with pediatric CNO, even for patients who have not undergone a bone biopsy, and have the potential to enable investigators to establish relatively homogeneous study populations for future clinical trials, Dr. Zhao said.