Chronic Recurrent Multifocal Osteomyelitis (CRMO)

Definition

An autoinflammatory, non-infective osteitis of childhood with relapsing multifocal bone lesions. It is the severe end of chronic non-bacterial osteomyelitis (CNO).

Aetiology

  • Innate immune dysregulation with reduced IL-10 and increased IL-1 activity
  • Monogenic forms include Majeed syndrome (LPIN2) and DIRA (IL1RN)
  • Associated with psoriasis, palmoplantar pustulosis, inflammatory bowel disease and SAPHO syndrome

Epidemiology

  • Median onset about 9 years
  • Girls affected about twice as often as boys

Clinical Features

  • Insidious bone pain, swelling and limp, often without fever
  • Metaphyses of long bones, clavicle, spine and pelvis are frequent sites
  • Medial clavicle involvement is a strong pointer
  • Symmetrical lesions with relapses and remissions over years

Investigations

  • Inflammatory markers normal or mildly raised, with negative blood cultures
  • Radiographs show lytic and sclerotic metaphyseal lesions, sometimes with hyperostosis
  • Whole body MRI detects silent lesions, often in the spine
  • Biopsy shows sterile chronic inflammation and excludes malignancy
  • Bristol criteria allow diagnosis without biopsy with multifocal or clavicular disease and CRP under 30 mg/L
  • Jansson score combines clinical and imaging variables to support diagnosis

Differential Diagnosis

Management

  • NSAIDs. First line, controlling symptoms in most children
  • Bisphosphonates. Pamidronate for spinal disease, vertebral collapse or NSAID failure
  • TNF inhibitors. For refractory disease or associated psoriasis or bowel disease
  • Antibiotics. No benefit once infection is excluded

Complications

  • Vertebral collapse and kyphosis
  • Leg length inequality and angular deformity from physeal involvement

Prognosis

  • Relapsing course in most, with persistent disease into adulthood in some

References

  1. Roderick MR, Shah R, Rogers V, Finn A, Ramanan AV. Chronic recurrent multifocal osteomyelitis (CRMO) – advancing the diagnosis. Pediatr Rheumatol Online J. 2016, 14(1), 47. PubMed
  2. Roderick MR, Sen ES, Ramanan AV. Chronic recurrent multifocal osteomyelitis in children and adults. Current understanding and areas for development. Rheumatology (Oxford). 2018, 57(1), 41-8. PubMed
  3. Jansson A, Renner ED, Ramser J, Mayer A, Haban M, Meindl A, Grote V, Diebold J, Jansson V, Schneider K, Belohradsky BH. Classification of non-bacterial osteitis. Retrospective study of clinical, immunological and genetic aspects in 89 patients. Rheumatology (Oxford). 2007, 46(1), 154-60. PubMed

Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 19 October 2026.