Incidence of chronic recurrent multifocal osteomyelitis in children and adolescents in the UK and Republic of Ireland

Abstract

Objectives: Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic non-bacterial osteomyelitis (CNO), is a rare autoinflammatory condition affecting the bones in children and teenagers. The actual incidence of CRMO remains uncertain. The objective of this study was to identify the incidence of CRMO in children and young people under the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI). We also aimed to delineate the demographics, clinical presentation, investigations, initial management and healthcare needs for children and adolescents with CRMO.

Methods: We conducted monthly surveys among all paediatric consultants and paediatric orthopaedic surgeons to identify patients newly diagnosed with CRMO between October 2020 and November 2022. A standardized questionnaire was sent to reporting clinicians to collect further information.

Results: Over the surveillance period, 288 patients were reported, among which, 165 confirmed and 20 probable cases were included in the analysis. The highest incidences were among 8-10 year-olds. A two-to-one female-to-male difference in incidence was observed, and male patients were more likely to present with multifocal disease. A negative correlation was observed between reporting clavicular and leg pain. Investigation-wise, 80.0% of patients were reported to have undergone whole-body MRI and 51.1% had bone biopsies. The most common initial treatments were NSAIDs (93.9%) and bisphosphonates (44.8%).

Conclusion: This study estimates an average annual CRMO incidence of 0.65 cases per 100 000 children and adolescents in the UK and ROI. These findings establish a crucial baseline for ongoing research and improvement in the care of individuals with CRMO.

Keywords: CNO; CRMO; auto-inflammatory; incidence; osteomyelitis; surveillance.

Figure 1.

Schematic summary of reported cases from BPSU and BSCOS. ^aBSCOS reported cases which had no paediatric involvement (n=6). ^bThese cases were initially reported as suspected CRMO but diagnoses were changed on subsequent correspondence with the reporting physicians. The final diagnoses were: one Langerhans cell histiocytosis, one stress fracture, one post-traumatic thoracic vertebral changes, one idiopathic juvenile osteoporosis, four unknown. ^cBoth cases were discussed in the study management group, and one was in keeping with infectious osteomyelitis (CRP 81, MRSA in multiple blood cultures and images in keeping with infectious osteomyelitis), one excluded as there was no evidence of any abnormality on imaging. BPSU: British Paediatric Surveillance Unit; BSCOS: British Society for Children’s Orthopaedic Surgery; CRMO: chronic recurrent multifocal osteomyelitis

Figure 2.

Age of onset and number of reported painful sites. (A) Bar chart of age at onset of symptoms, comparing male and female patients. (B) Density graph of number of reported painful sites per patient, comparing male and female patients. (C) Body map of reported sites of bone pain (left), with table of reported sites of bone pain split by gender (right)

Figure 3.

Investigations and management. (A) Bar chart showing the percentages of patients having had different imaging modalities and bone biopsy. (B) Table of reported CRP values. If the test had been done more than once at the time of reporting, the clinician was asked to record the highest value. (C) Analysis of positive histopathology characteristics from the bone biopsy reports received (n = 56). (D) Treatment received at the time of reporting. *Bisphosphonates: of 72 patients reported to use bisphosphonates, pamidronate = 58, zoledronate = 14. **Biologics: of six patients reported to use biologics, vedolizumab = 2, etanercept = 1, infliximab = 1, ustekinumab = 1, adalimumab = 1

Figure 4.

Health utilization & patient function. (A) Bar chart showing the percentage of patients with CRMO diagnosed by each specialty. (B) Utilization of allied health professionals at time of reporting. *Denominator for referrals to physiotherapy was 177, whereas denominator for referrals to all other AHPs was 176 due to missing data. (C) Impact of CRMO on schooling at presentation. (D) Impact of CRMO on mobility at presentation. AHP: Allied Health Professions; CAMHS: Child and Adolescent Mental Health Services; CMRO: chronic recurrent multifocal osteomyelitis