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Chronic Recurrent Multifocal Osteomyelitis

  • Chronic Recurrent Multifocal Osteomyelitis (CRMO) or Chronic Nonbacterial Osteomyelitis (CNO) is regarded as an autoinflammatory condition but as yet aetiology is unclear and there is no diagnostic test.
  • CRMO presents similarly to bacterial osteomyelitis with pain - often in multiple sites with bone or joint swelling - however by definition, the investigations for infection are negative and cultures are sterile. 
  • The emergence of bony swelling, with or without pain, is always a concern for red flag conditions; malignancy and infection must be excluded and multidisciplinary input is often needed to establish the correct diagnosis; children will often need extensive investigations including imaging and potentially biopsy of bone to establish the diagnosis. 
  • The involved sites in CRMO present with recurring episodes of bone pain, sometimes with swelling of the bone contiguous to the joint.
    • Presentation can be insidious with or without systemic features. 
    • Typical affected bones are the clavicle, long bones (tibia), ribs and vertebrae or pelvis with some lesions being apparently asymptomatic and detected with imaging. The affected area, if superficial can be swollen and warm but not red. 
    • The pain is usually worse at night and can affect function and mobility. 
    • Systemic and constitutional symptoms are often absent. Fever occurs in some children but most children are well appearing.
  • Blood tests, cultures and imaging (radiographs, ultrasound and sometimes CT or MRI) are needed. Gram stain cultures are required and tests for mycobacterial infection may also be needed. Biopsy may be needed to exclude malignancy.
  • There are usually high inflammatory markers (ESR, CRP, procalcitonin), high white cell count (neutrophils) and these guide clinical progress and response to treatment.
    • CRP is a better predictor than ESR for acute infection. 
    • Inflammatory markers can however be normal to mildly elevated.
  • Radiographs may be normal or show fluid or soft tissue swelling or increased joint space. Bony changes may not be apparent for 2-3 weeks.
    • Ultrasound may show joint effusion and is useful to aid aspiration (particularly the hip joint).
    • MRI is very sensitive to early changes and identify bone involvement. Isotope bone scan (increased uptake or hot spots) can be useful if MRI is not available.
  • Antibiotics are usually given empirically whilst awaiting cultures. Antibiotics are usually continued for several weeks (IV) and then oral, pending clinical progress and blood tests (acute phase reactants - ESR, CRP - and white cell count).
  • Analgesia and resting the joint / limb (splinting) are important.
    • NSAIDS for symptomatic relief and this may suffice for some patients at the mild end of the spectrum. 
  • Intravenous pamidronate (a biphosphonate treatment) is helpful to alleviate pain and reduce disease activity in CRMO.
  • Systemic immunosuppression is used for refractory disease or where there is intolerance to pamidronate. Clinical trials are in progress.
  • Patients require long term specialist supervision. Support for the family is important. 


Zhao Y, Ferguson PJ. Chronic Nonbacterial Osteomyelitis and Chronic Recurrent Multifocal Osteomyelitis in Children. Pediatr Clin North Am. 2018 Aug;65(4):783-800. doi: 10.1016/j.pcl.2018.04.003. PMID: 30031498.

Autoinflammatory Alliance: https://www.nomidalliance.com/compchart.php - a summary to demonstrate the overlap between the spectrum of diseases currently identified. 

FMF (Familial Mediterranean Fever) & AID (AutoImmuneDiseases) Global Association: https://www.fmfandaid.org/disease

PRINTO (Paediatric Rheumatology International Trials Organisation) : https://www.printo.it/pediatric-rheumatology/GB/info/sub/11/Autoinflammatory-Diseases - includes information sheets that can be downloaded for families. 

The Autoinflammatory Alliance provides more information and resources for families http://autoinflammatory.org