Evaluation of chronic recurrent multifocal osteitis in children by whole-body magnetic resonance imaging

doi:10.1016/j.jbspin.2011.12.001

Joint Bone Spine

Volume 79, Issue 6, December 2012, Pages 616-620

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Abstract

Objectives

Chronic recurrent multifocal osteomyelitis (CRMO) is a non-infectious inflammatory bone disease of unknown origin. The extension of CRMO is currently evaluated with bone scintigraphy. The objectives of our study are to describe the results of the non-invasive whole-body magnetic resonance imaging (WB MRI) procedure in children with CRMO, and to discuss the interest of WB MRI in CRMO's follow-up.

Methods

We performed a retrospective chart review of children followed for CRMO in the French center for auto-inflammatory disorders, selecting those who had a WB MRI at diagnosis and/or during follow-up. Clinical, biological, pathological and imaging findings were depicted.

Results

There were six girls and three boys, aged 8 to 14 years. All had multiple painful localizations with increased inflammatory markers, except one. The most frequent sites involved on WB MRI were the pelvis, the femurs and the tibias. We also described extra-osseous lesions (intra-articular effusion, myositis) and for the first time polyseritis that could not be caught by X-rays or scintigraphy. Comparison with scintigraphy in three patients showed that spinal, pelvic and femoral lesions were better seen with WB MRI. WB MRI at 12 months follow-up was available in five patients, showing a clear improvement in four of them. Surprisingly, the last patient had a clinical improvement with worsening lesions on WB MRI.

Conclusion

The WB MRI may contribute to the diagnosis and facilitate the follow-up of children with CRMO. This non-invasive, non-irradiating procedure will also allow depicting more precisely the natural history of bone and extra-osseous lesions in CRMO.

Introduction

Chronic recurrent multifocal osteomyelitis (CRMO) is a non-infectious inflammatory bone disease of unknown origin, first described by Giedion in 1972 [1]. Multifocal lytic bone lesions with swelling and pain are the most characteristic features of the disease. CRMO may be part of a spectrum of diseases where isolated bone inflammation could be the pediatric presentation of SAPHO syndrome, which includes synovitis, acne, pustulosis, hyperostosis, and osteitis.

The natural history of CRMO is unpredictable, often characterized by a prolonged course with exacerbations and spontaneous remissions. CRMO follow-up studies [2] suggested a good clinical outcome even though a minority of patients could have a severe and prolonged disease course despite intensive treatments. The functional outcome may be compromised due to growth alteration and inequality of lower limbs length.

The cause for CRMO remains poorly understood but an underlying auto-inflammatory disorder is currently discussed. Indeed, a murine model of CRMO was shown to be due to mutations of the PSTPIP2 gene, located in the chromosome 18 [3]. Several human models of inherited CRMO belong to syndromes associations such as Majeed syndrome – microcytic congenital dyserythropoietic anemia, failure to thrive and joint flexion contractures – linked to LPIN2 gene mutations [4], and DIRA syndrome – pustulosis, periostitis, osteomyelitis, a disease due to recessive mutations of the IL-1Ra gene [5]. The existence of familial cases reinforces the hypothesis of a strong genetic component. One genetic study on human CRMO using multiplex families and trios also identified a susceptibility locus in the chromosome 18 [6]. However, candidate gene analyses did not find any mutation in the PSTPIP2 gene in patients affected with sporadic or seemingly inherited SAPHO syndromes [7].

The diagnosis of CRMO is made on clinical evaluation after exclusion of other causes of bony inflammation processes, especially infections and tumors. Confirmation is generally provided by histology.

The management of patients with CRMO is still challenging. The evaluation of disease activity is quite difficult because there is no clear correlation between clinical findings, inflammatory markers and radiological findings. Standard X-rays remain normal at the beginning of the disease. Bone scintigraphy is currently used in order to prove the multiplicity of bone lesions [8].

Magnetic resonance imaging is a non-invasive imaging procedure and is highly sensitive to detect and analyze inflammatory lesions, particularly those located out of the bone [9]. Whole-body magnetic resonance imaging (WB MRI) has successfully been used to detect multifocal disorders in other pathologies such as metastatic cancer or psoriatic rheumatism [10], [11]. Because CRMO is a multifocal illness, evaluation of CRMO with WB MRI might be very useful.

So far, only one study focused on the use of WB MRI applied to CRMO diagnosis in 13 patients [12], and WB MRI has never been compared with bone scintigraphy, which is currently the most widely used imaging procedure for CRMO diagnosis and follow-up.

The aims of our study are precisely to describe WB MRI results when applied to the CRMO population, and to discuss the interest of WB MRI in CRMO diagnosis, outspread and follow-up.

Section snippets

Patients

We performed a retrospective chart review of 17 children with CRMO, who are currently followed in the tertiary care pediatric rheumatology center of Bicêtre, University of Paris-Sud, France. CRMO diagnosis was based on multifocal typical osseous lesions, biological inflammation, and response to NSAID treatment and for most of them confirmed by histological examination.

Selection criteria included diagnosis of CRMO (or SAPHO), pediatric age and whole-body magnetic resonance imaging examination at

Patients

Nine patients were included in this study, six girls and three boys, whose ages at onset ranged from 8 to 14 years. Patients’ characteristics are shown in Table 1. All of them had multiple painful sites. Symptoms were present 1 to 18 months (median: 2 months) before diagnosis. Three of them had a familial history: parents with CRMO or SAPHO for two of them and psoriasis in the last family.

Each patient first received antibiotics for suspicion of bone infection.

Six out of 9 patients underwent

Discussion

In our study as reported in the literature, the majority of CRMO cases occurred in females [2], [8], [12], [13], [14] with a median age at onset of the disease of 10 years [2], [8], [13]. Delay up to CRMO diagnosis was usually short. We found family history in three patients among 9, and this particular fact has not been mentioned in literature. In addition, clinical and biological inflammatory markers were variable and there was sometimes a discrepancy between ESR and CRP. Biological

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

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Original articleEvaluation of chronic recurrent multifocal osteitis in children by whole-body magnetic resonance imaging

Abstract

Objectives

Methods

Results

Conclusion

Introduction

Section snippets

Patients

Patients

Discussion

Disclosure of interest

Bone

Eur J Radiol

Eur J Radiol

Eur J Radiol

Joint Bone Spine

Best Pract Res Clin Rheumatol

Subacute and chronic “symmetrical” osteomyelitis

Ann Radiol

Original article
Evaluation of chronic recurrent multifocal osteitis in children by whole-body magnetic resonance imaging