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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2005 Feb;64(2):279–285. doi: 10.1136/ard.2004.023838

Chronic non-bacterial osteomyelitis in children

H Girschick 1, P Raab 1, S Surbaum 1, A Trusen 1, S Kirschner 1, P Schneider 1, T Papadopoulos 1, H Muller-Hermelink 1, P Lipsky 1
PMCID: PMC1755336  PMID: 15647436

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.

Full Text

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Figure 2.

Figure 2

 Clinical synopsis of a 20 year old male patient with a history of 7.5 years of CNO.

Figure 1.

Figure 1

 Bone (left) and joint (right) involvement in 30 paediatric patients with CNO.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amor B., Dougados M., Listrat V., Menkes C. J., Dubost J. J., Roux H., Benhamou C., Blotman F., Pattin S., Paolaggi J. B. Evaluation des critères des spondylarthropathies d'Amor et de l'European Spondylarthropathy Study Group (ESSG). Une étude transversale de 2,228 patients. Ann Med Interne (Paris) 1991;142(2):85–89. [PubMed] [Google Scholar]
  2. Andersson R. Effective treatment with interferon-alpha in chronic recurrent multifocal osteomyelitis. J Interferon Cytokine Res. 1995 Oct;15(10):837–838. doi: 10.1089/jir.1995.15.837. [DOI] [PubMed] [Google Scholar]
  3. Appell R. G., Oppermann H. C., Becker W., Kratzat R., Brandeis W. E., Willich E. Condensing osteitis of the clavicle in childhood: a rare sclerotic bone lesion. Review of literature and report of seven patients. Pediatr Radiol. 1983;13(6):301–306. doi: 10.1007/BF01625953. [DOI] [PubMed] [Google Scholar]
  4. Bj0rkstén B., Boquist L. Histopathological aspects of chronic recurrent multifocal osteomyelitis. J Bone Joint Surg Br. 1980 Aug;62(3):376–380. doi: 10.1302/0301-620X.62B3.7410472. [DOI] [PubMed] [Google Scholar]
  5. Björkstén B., Gustavson K. H., Eriksson B., Lindholm A., Nordström S. Chronic recurrent multifocal osteomyelitis and pustulosis palmoplantaris. J Pediatr. 1978 Aug;93(2):227–231. doi: 10.1016/s0022-3476(78)80501-0. [DOI] [PubMed] [Google Scholar]
  6. Carr A. J., Cole W. G., Roberton D. M., Chow C. W. Chronic multifocal osteomyelitis. J Bone Joint Surg Br. 1993 Jul;75(4):582–591. doi: 10.1302/0301-620X.75B4.8331113. [DOI] [PubMed] [Google Scholar]
  7. Dougados M., van der Linden S., Juhlin R., Huitfeldt B., Amor B., Calin A., Cats A., Dijkmans B., Olivieri I., Pasero G. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum. 1991 Oct;34(10):1218–1227. doi: 10.1002/art.1780341003. [DOI] [PubMed] [Google Scholar]
  8. Giedion A., Holthusen W., Masel L. F., Vischer D. [Subacute and chronic "symmetrical" osteomyelitis]. Ann Radiol (Paris) 1972 Mar-Apr;15(3):329–342. [PubMed] [Google Scholar]
  9. Girschick H. J., Huppertz H. I., Harmsen D., Krauspe R., Müller-Hermelink H. K., Papadopoulos T. Chronic recurrent multifocal osteomyelitis in children: diagnostic value of histopathology and microbial testing. Hum Pathol. 1999 Jan;30(1):59–65. doi: 10.1016/s0046-8177(99)90301-5. [DOI] [PubMed] [Google Scholar]
  10. Girschick H. J., Krauspe R., Tschammler A., Huppertz H. I. Chronic recurrent osteomyelitis with clavicular involvement in children: diagnostic value of different imaging techniques and therapy with non-steroidal anti-inflammatory drugs. Eur J Pediatr. 1998 Jan;157(1):28–33. doi: 10.1007/s004310050761. [DOI] [PubMed] [Google Scholar]
  11. Goldenberger D., Künzli A., Vogt P., Zbinden R., Altwegg M. Molecular diagnosis of bacterial endocarditis by broad-range PCR amplification and direct sequencing. J Clin Microbiol. 1997 Nov;35(11):2733–2739. doi: 10.1128/jcm.35.11.2733-2739.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Handrick W., Hörmann D., Voppmann A., Schille R., Reichardt P., Tröbs R. B., Möritz R. P., Borte M. Chronic recurrent multifocal osteomyelitis--report of eight patients. Pediatr Surg Int. 1998 Dec;14(3):195–198. doi: 10.1007/s003830050485. [DOI] [PubMed] [Google Scholar]
  13. Hayem G., Bouchaud-Chabot A., Benali K., Roux S., Palazzo E., Silbermann-Hoffman O., Kahn M. F., Meyer O. SAPHO syndrome: a long-term follow-up study of 120 cases. Semin Arthritis Rheum. 1999 Dec;29(3):159–171. doi: 10.1016/s0049-0172(99)80027-4. [DOI] [PubMed] [Google Scholar]
  14. Helkimo M. Studies on function and dysfunction of the masticatory system. II. Index for anamnestic and clinical dysfunction and occlusal state. Sven Tandlak Tidskr. 1974 Mar;67(2):101–121. [PubMed] [Google Scholar]
  15. Huaux J. P., Esselinckx W., Meunier H., Malghem J., Maldague B., Nagant de Deuxchaisnes C. Pustulotic arthro-osteitis in children and adults. A report of 13 cases. Clin Exp Rheumatol. 1987 Apr-Jun;5(2):143–146. [PubMed] [Google Scholar]
  16. Huaux J. P., Esselinckx W., Rombouts J. J., Maldague B., Malghem J., Devogelaer J. P., Nagant de Deuxchaisnes C. Pustulotic arthroosteitis and chronic recurrent multifocal osteomyelitis in children. Report of three cases. J Rheumatol. 1988 Jan;15(1):95–100. [PubMed] [Google Scholar]
  17. Huber Adam M., Lam Pei-Yoong, Duffy Catherine M., Yeung Rae S. M., Ditchfield Michael, Laxer Dara, Cole William G., Kerr Graham H., Allen Roger C., Laxer Ronald M. Chronic recurrent multifocal osteomyelitis: clinical outcomes after more than five years of follow-up. J Pediatr. 2002 Aug;141(2):198–203. doi: 10.1067/mpd.2002.126457. [DOI] [PubMed] [Google Scholar]
  18. Hummell D. S., Anderson S. J., Wright P. F., Cassell G. H., Waites K. B. Chronic recurrent multifocal osteomyelitis: are mycoplasmas involved? N Engl J Med. 1987 Aug 20;317(8):510–511. [PubMed] [Google Scholar]
  19. Jani L., Remagen W. Primary chronic osteomyelitis. Int Orthop. 1983;7(2):79–83. doi: 10.1007/BF00266455. [DOI] [PubMed] [Google Scholar]
  20. Job-Deslandre C., Krebs S., Kahan A. Chronic recurrent multifocal osteomyelitis: five-year outcomes in 14 pediatric cases. Joint Bone Spine. 2001 May;68(3):245–251. doi: 10.1016/s1297-319x(01)00276-7. [DOI] [PubMed] [Google Scholar]
  21. Jurik A. G., Møller B. N. Chronic sclerosing osteomyelitis of the clavicle. A manifestation of chronic recurrent multifocal osteomyelitis. Arch Orthop Trauma Surg. 1987;106(3):144–151. doi: 10.1007/BF00452200. [DOI] [PubMed] [Google Scholar]
  22. Jurik A. G., Møller B. N. Inflammatory hyperostosis and sclerosis of the clavicle. Skeletal Radiol. 1986;15(4):284–290. doi: 10.1007/BF00349816. [DOI] [PubMed] [Google Scholar]
  23. Jurik A. G., Møller B. N., Jensen M. K., Jensen J. T., Graudal H. Sclerosis and hyperostosis of the manubrium sterni. Rheumatol Int. 1986;6(4):171–178. doi: 10.1007/BF00541284. [DOI] [PubMed] [Google Scholar]
  24. Jurriaans E., Singh N. P., Finlay K., Friedman L. Imaging of chronic recurrent multifocal osteomyelitis. Radiol Clin North Am. 2001 Mar;39(2):305–327. doi: 10.1016/s0033-8389(05)70279-7. [DOI] [PubMed] [Google Scholar]
  25. Kahn M. F., Bouvier M., Palazzo E., Tebib J. G., Colson F. Sternoclavicular pustulotic osteitis (SAPHO). 20-year interval between skin and bone lesions. J Rheumatol. 1991 Jul;18(7):1104–1108. [PubMed] [Google Scholar]
  26. Kahn M. F., Chamot A. M. SAPHO syndrome. Rheum Dis Clin North Am. 1992 Feb;18(1):225–246. [PubMed] [Google Scholar]
  27. Krauspe R., Girschick H., Huppertz H. I. Lymphoplasmazelluläre Osteomyelitis. Orthopade. 1997 Oct;26(10):894–901. doi: 10.1007/PL00003339. [DOI] [PubMed] [Google Scholar]
  28. Le Goff P., Brousse A., Fauquert P., Guillet G., Leroy J. P. Arthropathies érosives thoraciques antérieures et intervertébrales associées à la pustulose palmoplantaire. Rev Rhum Mal Osteoartic. 1985 Jun;52(6):391–396. [PubMed] [Google Scholar]
  29. Leirisalo-Repo M. Enteropathic arthritis, Whipple's disease, juvenile spondyloarthropathy, uveitis, and SAPHO syndrome. Curr Opin Rheumatol. 1995 Jul;7(4):284–289. doi: 10.1097/00002281-199507000-00004. [DOI] [PubMed] [Google Scholar]
  30. Lissens M., Bruyninckx F., Rosselle N. Condensing osteitis of the clavicle. Report of two cases and review of the literature. Acta Belg Med Phys. 1990 Oct-Dec;13(4):235–240. [PubMed] [Google Scholar]
  31. Mollan R. A., Craig B. F., Biggart J. D. Chronic sclerosing osteomyelitis. An unusual case. J Bone Joint Surg Br. 1984 Aug;66(4):583–585. doi: 10.1302/0301-620X.66B4.6746696. [DOI] [PubMed] [Google Scholar]
  32. Pelkonen P., Ryöppy S., Jäskeläinen J., Rapola J., Repo H., Kaitila I. Chronic osteomyelitislike disease with negative bacterial cultures. Am J Dis Child. 1988 Nov;142(11):1167–1173. doi: 10.1001/archpedi.1988.02150110045017. [DOI] [PubMed] [Google Scholar]
  33. Petty R. E., Southwood T. R., Baum J., Bhettay E., Glass D. N., Manners P., Maldonado-Cocco J., Suarez-Almazor M., Orozco-Alcala J., Prieur A. M. Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol. 1998 Oct;25(10):1991–1994. [PubMed] [Google Scholar]
  34. Poujol A., Toesca S., Di Marco J. N., Rimet Y., Tissot Dupont H., Macé L., Sudan N., Panuel M., Turcat Y., Kelberine F. Ostéites récidivantes et Coxiella burnetti: relation avec l'ostéomyélite chronique récurrente multifocale. Arch Pediatr. 1998 Mar;5(3):291–294. doi: 10.1016/s0929-693x(97)89372-4. [DOI] [PubMed] [Google Scholar]
  35. Reinehr T., Bürk G., Michel E., Andler W. Chronic osteomyelitis in childhood: is surgery always indicated? Infection. 2000 Sep;28(5):282–286. doi: 10.1007/s150100070020. [DOI] [PubMed] [Google Scholar]
  36. Reith J. D., Bauer T. W., Schils J. P. Osseous manifestations of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. Am J Surg Pathol. 1996 Nov;20(11):1368–1377. doi: 10.1097/00000478-199611000-00008. [DOI] [PubMed] [Google Scholar]
  37. Schilling F., Coerdt W., Eckardt A., Full H., Hospach T., Kessler S., Köcher M., Kreitner K. F. Die Chronisch rekurrierende multifokale Osteomyelitis (CRMO)*: - Teil 2 Klinisch-radiologisch-histopathologische Studie zum kindlich-jugendlichen "Beckentyp" bei 11 Patienten - Klin Padiatr. 2001 Sep-Oct;213(5):277–284. doi: 10.1055/s-2001-17219. [DOI] [PubMed] [Google Scholar]
  38. Schilling F., Eckardt A., Kessler S. Die chronische rekurrierende multifokale Osteomyelitis. Z Orthop Ihre Grenzgeb. 2000 Nov-Dec;138(6):530–539. doi: 10.1055/s-2000-9597. [DOI] [PubMed] [Google Scholar]
  39. Schilling F., Kessler S. Die Chronische rekurrierende multifokale Osteomyelitis (CRMO)* - Teil 1 Ubersicht - Klin Padiatr. 2001 Sep-Oct;213(5):271–276. doi: 10.1055/s-2001-17218. [DOI] [PubMed] [Google Scholar]
  40. Schultz C., Holterhus P. M., Seidel A., Jonas S., Barthel M., Kruse K., Bucsky P. Chronic recurrent multifocal osteomyelitis in children. Pediatr Infect Dis J. 1999 Nov;18(11):1008–1013. doi: 10.1097/00006454-199911000-00015. [DOI] [PubMed] [Google Scholar]
  41. Schuster T., Bielek J., Dietz H. G., Belohradsky B. H. Chronic recurrent multifocal osteomyelitis (CRMO). Eur J Pediatr Surg. 1996 Feb;6(1):45–51. doi: 10.1055/s-2008-1066469. [DOI] [PubMed] [Google Scholar]
  42. Sundaram M., McDonald D., Engel E., Rotman M., Siegfried E. C. Chronic recurrent multifocal osteomyelitis: an evolving clinical and radiological spectrum. Skeletal Radiol. 1996 May;25(4):333–336. doi: 10.1007/s002560050091. [DOI] [PubMed] [Google Scholar]
  43. Tan B. S., Nayanar V., Mansberg R., Murray I. P., Rossleigh M. A. Two cases of chronic recurrent multifocal osteomyelitis: radiological and scintigraphic findings. Australas Radiol. 1996 Nov;40(4):437–441. doi: 10.1111/j.1440-1673.1996.tb00443.x. [DOI] [PubMed] [Google Scholar]
  44. Tröbs R., Möritz R., Bühligen U., Bennek J., Handrick W., Hörmann D., Meier T. Changing pattern of osteomyelitis in infants and children. Pediatr Surg Int. 1999 Jul;15(5-6):363–372. doi: 10.1007/s003830050600. [DOI] [PubMed] [Google Scholar]
  45. Uhl M., Leichsenring M., Krempien B. Chronisch rezidivierende multifokale Osteomyelitis. Rofo. 1995 Jun;162(6):527–530. doi: 10.1055/s-2007-1015930. [DOI] [PubMed] [Google Scholar]
  46. Van Howe R. S., Starshak R. J., Chusid M. J. Chronic, recurrent multifocal osteomyelitis. Case report and review of the literature. Clin Pediatr (Phila) 1989 Feb;28(2):54–59. doi: 10.1177/000992288902800201. [DOI] [PubMed] [Google Scholar]
  47. Vittecoq O., Said L. A., Michot C., Mejjad O., Thomine J. M., Mitrofanoff P., Lechevallier J., Ledosseur P., Gayet A., Lauret P. Evolution of chronic recurrent multifocal osteitis toward spondylarthropathy over the long term. Arthritis Rheum. 2000 Jan;43(1):109–119. doi: 10.1002/1529-0131(200001)43:1<109::AID-ANR14>3.0.CO;2-3. [DOI] [PubMed] [Google Scholar]
  48. Wagner Annette D., Andresen Jan, Jendro Michael C., Hülsemann Jan L., Zeidler Henning. Sustained response to tumor necrosis factor alpha-blocking agents in two patients with SAPHO syndrome. Arthritis Rheum. 2002 Jul;46(7):1965–1968. doi: 10.1002/art.10539. [DOI] [PubMed] [Google Scholar]
  49. Waldvogel K., Regnery R. L., Anderson B. E., Caduff R., Caduff J., Nadal D. Disseminated cat-scratch disease: detection of Rochalimaea henselae in affected tissue. Eur J Pediatr. 1994 Jan;153(1):23–27. [PubMed] [Google Scholar]
  50. Weihe S., Eufinger H., Terhaar O., König M., Machtens E. Mandibulabeteiligung bei der chronisch rekurrierenden multifokalen Osteomyelitis (CRMO) im Erwachsenenalter. Mund Kiefer Gesichtschir. 2000 May;4(3):187–192. doi: 10.1007/s100060050195. [DOI] [PubMed] [Google Scholar]
  51. Yu L., Kasser J. R., O'Rourke E., Kozakewich H. Chronic recurrent multifocal osteomyelitis. Association with vertebra plana. J Bone Joint Surg Am. 1989 Jan;71(1):105–112. [PubMed] [Google Scholar]

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