Objective
Chronic recurring multifocal osteomyelitis (CRMO) is a rare idiopathic autoinflammatory
skeletal disease that causes aseptic osteomyelitis, which leads to bone deformation, lesions and
pain. It mostly affects children and adolescents with a peak onset age between seven and twelve
years old. Typically, patients present with unspecific complaints including bone pain of
insidious onset, tenderness, and local swelling or limiting range of motion. The clinical course
can be monophasic or recurring pain exacerbations and remissions. It can be unifocal or
multifocal and typically affects the metaphysis of long bones. The localization of these lesions
varies from one patient to another but common sites of CRMO are: tibia, pelvis, femur, clavicle,
calcaneum, vertebrae and mandible. The initial therapy for most children is nonsteroidal antiinflammatory
drugs (NSAID) which are the first line of treatment. However, in cases of chronic
or acute relapsing CRMO, a second line treatment (anti TNF, bisphosphonates, steroids, and
methotrexate) may be necessary. Management of CRMO often presents difficulty in identifying
the patients who are likely to have spontaneous resolution of symptoms and those who are likely
to suffer in the long term. The objective of this study is to try to identify factors that are
associated with worse prognosis and that could explain why certain patients need second line
treatment.
Methods:
This is an observational retrospective cohort study that was based on the description of the data
we collected from the Juvenile Inflammatory Rheumatism cohort (JIRcohorte). The study
population included pediatric patients (< 18 years old) diagnosed with CRMO. These patients
are followed-up in the Western Switzerland Pediatric Immuno-Rheumatology Unit consultation
in Geneva at the HUG (Geneva University Hospital) and in Lausanne at the CHUV (Lausanne
University Hospital). The criteria we analyzed were sex, age at the onset of symptoms, age at
diagnosis, diagnostic delay, localization and number of lesions at diagnosis and the association
or not to other pathologies such as arthritis, psoriasis, acne fulminans, IBD, uveitis. Patients
were divided into two groups depending on the treatment they received. The patients in the first
group (group 1) were all treated with NSAIDs. The patients in the second group (group 2)
required a second line treatment.
Results:
We included 28 CRMO patients (19F/9M). 15/28 patients (54%) presented with a multifocal
affectation at diagnosis, involving the lower extremities (54%), pelvic bones (23%) and spine
(15%) most frequently. 13/28 patients (46%) presented with a unifocal involvement at diagnosis
affecting the tibia most frequently (46%) followed by the clavicle (31%). There were 20 patients
in group 1 among which 70% were females. The median age at onset of symptoms was 9.7
years (range: 2.6-14.5), the median age at diagnosis was 10.6 years (range: 3.3-15.0) and
diagnostic delay was 202 days (range: 101-1329). 11/20 (55%) patients presented with a
unifocal involvement at diagnosis. Long bones of the lower extremities (75%) and long bones
of the upper extremities (25%) were the most commonly affected at diagnosis. 1 patient (5%)
also presented with IBD.
3
There were 8 patients in group 2 among which 62.5% were females. The median age at onset
of symptoms was 10.1 years (range: 6.4-14.5), the median age at diagnosis was 10.8 years
(range: 7.2-15.5) and diagnostic delay was 274 days (range: 236-1035). 75% presented with a
multifocal involvement at diagnosis. Long bones of the lower extremities (62.5%), pelvic bones
(62.5%) and spine (37.5%) were the most commonly affected bones at diagnosis. 3 patients
(37.5%) presented with associated pathologies including enthesitis-related arthritis and uveitis.
Conclusion:
In this study, we observed that there were proportionally more males compared to females that
presented with more severe forms of CRMO. Patients with a more severe form of the disease
had a longer diagnostic delay. They were also more frequently affected with associated
pathologies such as uveitis as well as enthesitis-related arthritis. Moreover, these patients
presented more often with a multifocal involvement at diagnosis and the spine and pelvic bones
were more frequently involved. Since the affection of the vertebral column can lead to spine
compression fractures and have a severe impact on the evolution of the disease, it is important
to treat them adequately as soon as possible as this could affect the patients’ quality of life.