Chronic non-bacterial osteomyelitis in children

Abstract

Background: Chronic recurrent multifocal osteomyelitis (CRMO) in children is a chronic non-suppurative inflammation involving multiple sites. Some children affected by chronic non-bacterial osteomyelitis (CNO) do not have multiple lesions or a recurrent course. Objective: To characterise the long term outcome of children with the full spectrum of CNO. Methods: 30 children diagnosed with CNO were followed up for a mean of 5.6 years and their disease assessed using a clinical score, multiple imaging, and a diagnostic biopsy, including extensive microbial analysis. Results: 9 patients had unifocal non-relapsing disease, 3 unifocal lesions with relapses, 9 multifocal lesions without relapses, and 9 multifocal lesions with relapses (CRMO). Granulocytes were present significantly more often in CRMO than in unifocal and non-recurrent lesions. Pustulosis was more common in multifocal cases regardless of recurrence. Mean duration of treatment in 15 children with a single occurrence was 9.2 months. Naproxen treatment was generally effective. Naproxen treatment in 12 patients with relapses lasted 25 months. However, 7 of these were not effectively treated with naproxen alone. Five were treated with oral glucocorticoids for 27 days in addition to naproxen, which induced remission in four, lasting for at least 1.5 years. Longitudinal growth of affected bones was not altered, except for the development of hyperostosis. Conclusion: CNO is a spectrum of inflammatory conditions, with CRMO being the most severe. Most children with CNO have a favourable outcome of the disease. Oral glucocorticoids may be necessary in severe recurrent cases.

Characteristics and outcomes of chronic non-bacterial osteitis in children

“…In agreement with the literature, the clavicle was one of the most commonly affected bones (34% of patients) (25). With 60 bone lesions identified, the lower extremity was the most affected part of the skeleton, similar to the findings of previous studies (15,16,26). A previous study showed an association between CNO and different skin manifestations, such as palmoplantar pustulosis and acne, in up to 23% of children (24).…”

“…In our study, 62% of patients with CNO achieved remission after monotherapy with NSAIDs, which is lower than the value reported in most earlier investigations (maximum 80%) (16,24). In contrast, some studies have reported that only 13% of patients achieved clinical remission using NSAIDs (28).…”

“…The first-line therapy for CNO is non-steroidal anti-inflammatory drugs (NSAIDs) (19). Among the second-line therapies, corticosteroids, methotrexate, sulfasalazine, TNF-α inhibitors, and bisphosphonates are used (16,(20)(21)(22). The aim of this study was to determine patient characteristics, clinical presentation, pattern of involvement, treatment, and outcome of patients with CNO.…”

“…Even the pathophysiology of CNO is not completely known; there is evidence of an imbalance between pro-[interleukin-6 and tumor necrosis factor α (TNF-α)] and anti-inflammatory (interleukin-10) cytokines in patients with CNO (14). Children frequently have mild to moderately increased levels of inflammatory markers (7,15,16). Nowadays, CNO is usually diagnosed using magnetic resonance imaging (MRI) or through histological examination of bone biopsies, which reveal chronic inflammation and sclerosis without an infectious agent (17, 18).…”

Chronic Non-Bacterial Osteitis/Chronic Recurrent Multifocal Osteomyelitis

“…In 2005, the term CNO was coined to describe all of these disorders, and the current understanding is that non-infectious inflammatory bone disorders present a clinical spectrum within which CRMO is the most severe form (Girschick, Raab et al 2005). There have been further attempts to classify patients into defined groups (unifocal nonrecurrent, unifocal recurrent, multifocal nonrecurrent, multifocal recurrent) to establish diagnostic criteria and to find prognostic indicators, although such classification criteria have not been uniformly adapted (Beck, Morbach et al 2010).…”