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Review
. 2020 Jul 23;22(9):52.
doi: 10.1007/s11926-020-00928-1.

New Insights into Adult and Paediatric Chronic Non-bacterial Osteomyelitis CNO

Christian M Hedrich  1   2 , Henner Morbach  3 , Christiane Reiser  4 , Hermann J Girschick  5   6
Affiliations
Review

New Insights into Adult and Paediatric Chronic Non-bacterial Osteomyelitis CNO

Christian M Hedrich et al. Curr Rheumatol Rep. .

Abstract

Purpose of review: To describe in detail the clinical synopsis and pathophysiology of chronic non-bacterial osteomyelitis and SAPHO syndrome.

Recent findings: Chronic non-bacterial osteomyelitis (CNO) has been identified as a disease entity for almost 50 years. This inflammatory bone disorder is characterized by osteolytic as well as hyperostotic/osteosclerotic lesions. It is chronic in nature, but it can present with episodic flairs and phases of remission, which have led to the denomination "chronic recurrent osteomyelitis", with its severe multifocal form "chronic recurrent multifocal osteomyelitis" (CRMO). For almost three decades, an infectious aetiology had been considered, since especially Propionibacterium acnes had been isolated from bone lesions of individual patients. However, this concept has been challenged since long-term antibiotic therapy did not alter the course of disease and modern microbiological techniques (including PCR) failed to confirm bone infection as an underlying cause. Over recent years, a profound dysregulation of cytokine expression profiles has been demonstrated in innate immune cells of CNO patients. A hallmark of monocytes from CNO patients is the failure to produce immune regulatory cytokines interleukin-10 (IL-10) and IL-19, which have been linked with genetic and epigenetic alterations. Subsequently, a significant upregulation of pro-inflammatory, NLRP3 inflammasome-dependent cytokines (IL-1β and TNF-α), has been demonstrated. The current knowledge on CNO, the underlying molecular pathophysiology, and modern imaging strategies are summarized; differential diagnoses, treatment options, outcome measures, as well as quality of life studies are discussed.

Keywords: Bone autoinflammation; Chronic non-bacterial osteomyelitis; Chronic recurrent multifocal osteomyelitis; Lymphoplasmacellular osteomyelitis.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Differential diagnosis of chronic non-bacterial osteomyelitis in childhood
Fig. 2
Fig. 2
Whole body MRI of CNO. Whole body MRI using turbo inversion recovery measurement (TIRM) (a) of a 12-year-old male patient exhibiting symmetrical inflammatory bone lesions of the distal radius (b), distal tibiae (e), iliac bones (c), the sacral bone (d) and metatarsal bones (f). Knees were not affected (g)
Fig. 3
Fig. 3
Proposed treat-to-target protocol for childhood CNO
See this image and copyright information in PMC

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

    1. Giedion A, Holthusen W, Masel LF, Vischer D. Subacute and chronic “symmetrical” osteomyelitis. Ann Radiol (Paris) 1972;15(3):329–342. - PubMed
    1. Girschick HJ, Raab P, Surbaum S, Trusen A, Kirschner S, Schneider P, et al. Chronic non-bacterial osteomyelitis in children. Ann Rheum Dis. 2005;64(2):279–285. - PMC - PubMed
    1. Jurik AG, Helmig O, Ternowitz T, Moller BN. Chronic recurrent multifocal osteomyelitis: a follow-up study. J Pediatr Orthop. 1988;8(1):49–58. - PubMed
    1. Girschick HJ, Zimmer C, Klaus G, Darge K, Dick A, Morbach H. Chronic recurrent multifocal osteomyelitis: what is it and how should it be treated? Nat Clin Pract Rheumatol. 2007;3(12):733–738. - PubMed
    1. Girschick HJ, Huppertz HI, Harmsen D, Krauspe R, Muller-Hermelink HK, Papadopoulos T. Chronic recurrent multifocal osteomyelitis in children: diagnostic value of histopathology and microbial testing. Hum Pathol. 1999;30(1):59–65. - PubMed
Personal Communication
    1. Assmann G et al. 2020 submitted, accepted, in press
    1. Aßmann G, Köhm M, Schuster V, Behrens F, Mössner R, Magnolo N, Oji V, Burkhardt H, Hüffmeier U. Genetic variants in FBLIM1 gene do not contribute to SAPHO syndrome and chronic recurrent multifocal osteomyelitis in typical patient groups n.d.. - PMC - PubMed
    1. BMC Medical Genetics. in press; MGTC-D-19-00527R5.

Supplementary concepts