Chronic recurrent multifocal osteomyelitis (CRMO): a non-infectious bone inflammation

Osteomyelitis means inflammation of bone. In its usual form it is a bone infection. The NHS describes osteomyelitis as a painful bone infection treated with antibiotics, usually for 4 to 6 weeks and for up to 12 weeks if severe. CRMO is different: bone becomes inflamed with no infectious organism being the cause.

A 2021 review in the journal Children describes chronic nonbacterial osteomyelitis (CNO) as an auto-inflammatory bone disorder, first described in 1972, with a wide spectrum from unifocal (one site) to multifocal lesions. When lesions are multifocal it is also referred to as chronic recurrent multifocal osteomyelitis (CRMO). Other terms used over time include SAPHO syndrome and nonbacterial osteomyelitis.

Please note that this review comes from a Swiss paediatric rheumatology group. No UK patient guide for CRMO could be read for this page, so general statements are sourced from this review and from NHS information on bone infection for contrast. A UK paediatric rheumatology team will tailor advice to the individual.

The review states that the median age at diagnosis in children is 10 years, with most cases reported between 8 and 13, and that in European cohorts females appear more likely to be affected, at a female-to-male ratio of about 2 to 1. It adds that incidence varies across geographic areas, which is thought to be due to awareness rather than ethnic or environmental factors, and that diagnostic delay is common, with a mean interval of about 12 months between symptom onset and diagnosis.

CNO is associated with other chronic inflammatory conditions in up to 20% of cases, according to the review, including juvenile idiopathic arthritis, spondylarthritis, inflammatory bowel disease and skin conditions such as psoriasis and severe acne.

CNO usually presents with insidious, recurrent bone pain at one or more sites. Pain intensity varies and is mostly reported in the morning and during the night, which can disturb sleep. This pattern can lead to a mistaken diagnosis of growing pains and delay recognition. Pain may come with local swelling and limited use of the limb.

Inflammation can occur at any site in the skeleton, although the ends of the long bones (the metaphyses) are the most frequently involved in children. Involvement of the sternum, clavicle or jaw is suggestive. Spinal involvement is seen in up to about a third of cases and is an important prognostic factor because it can be complicated by vertebral fracture. Arthritis develops in approximately 40% of cases, and fever or fatigue is reported in 17 to 20%.

Many lesions are silent. The review says lesions can be asymptomatic in about half or more of patients, which is why imaging of the whole body is valuable.

Persistent or recurring bone pain in a child, especially pain that wakes them at night, is a reason to see a GP. Because bone infection is also a possibility, the NHS advises asking for an urgent GP appointment or contacting NHS 111 for pain, swelling, redness and warmth over a bone with a very high temperature and feeling generally unwell. It also advises taking a child to a GP if they do not want to use an arm or leg and seem irritable. Infection needs prompt treatment, so these symptoms should not be waited out.

CNO and CRMO remain a diagnosis of exclusion. The review notes there is no specific laboratory finding, that inflammatory markers such as CRP and ESR are raised in a variable proportion of patients and that diagnostic criteria proposed so far have not been validated in prospective studies.

Imaging is central. Whole-body MRI is the gold standard because it detects inflamed sites sensitively and avoids radiation. X-ray is often the first test and may be normal early on. A bone biopsy may be needed to exclude cancer or infection, particularly where there is a single lesion, an unusual location, very early onset or an atypical response to treatment. The differential diagnosis includes bone tumours, leukaemia, infectious osteomyelitis and growing pains.

The review states that the aims of treatment are pain control, reducing inflammation and preventing complications, and that treatment remains empirical because most published studies are small retrospective case series. NSAIDs are frequently the first-line treatment. In persistent bone pain or inflammation after about three months of NSAID treatment a second-line treatment is considered.

Second-line options listed include short courses of glucocorticoids when other diagnoses have been ruled out, methotrexate, TNF-alpha blockers and bisphosphonates. The review reports that bisphosphonates have been used for almost 20 years and that they may be proposed early where the spine or jaw is involved. Decisions about which drug to use sit with a paediatric rheumatology or specialist team.

The review says the disease course is unpredictable. It can be self-limited or recurrent, and uncontrolled lesions can lead to fractures and deformities, which is why long-term follow-up matters. In practice, follow-up includes checking pain, activity, growth and repeat imaging as advised by the specialist team.

Care in the UK usually involves a paediatric or adult rheumatology team, radiology for MRI and sometimes orthopaedics for biopsy. Because the condition is rare, referral to a specialist centre may be needed. Private rheumatology and imaging are options, but a rare diagnosis benefits from a team that regularly sees similar cases and shares care with the NHS.