Chronic Recurrent Multifocal Osteomyelitis

Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease occurring primarily in children and adolescents. Episodes of systemic inflammation occur due to immune dysregulation without autoantibodies, pathogens or antigen-specific T cells. CRMO is characterised by the insidious onset of pain with swelling and tenderness over the affected bones. Clavicular involvement was the classical description; however, the metaphyses and epiphyses of long bones are frequently affected. Lesions may occur in any bone, including vertebrae. Characteristic imaging includes bone oedema, lytic areas, periosteal reaction and soft tissue reaction. Biopsies from affected areas display polymorphonuclear leucocytes with osteoclasts and necrosis in the early stages. Subsequently, lymphocytes and plasma cells predominate followed by fibrosis and signs of reactive new bone forming around the inflammation. Diagnosis is facilitated by the use of STIR MRI scanning, potentially obviating the need for biopsy and unnecessary long-term antibiotics due to incorrect diagnosis. Treatment options include non-steroidal anti-inflammatory drugs and bisphosphonates. Biologics have been tried in resistant cases with promising initial results. Gene identification has not proved easy although research in this area continues. Early descriptions of the disease suggested a benign course; however, longer-term follow up shows that it can cause significant morbidity and longer term disability.

Although it has always been thought of as very rare, the prevalence is likely to be vastly underestimated due to poor recognition of the disease.

Keywords

Osteogenesis Imperfecta Periosteal Reaction Chronic Recurrent Multifocal Osteomyelitis Bony Lesion Bone Oedema 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Giedion A, Holthusen W, Masel LF, Vischer D (1972) Subacute and chronic “symmetrical” osteomyelitis. Ann Radiol 15(3):329–342 (Paris)PubMedGoogle Scholar
  2. 2.
    Björkstén B, Gustavson KH, Eriksson B, Lindholm A, Nordström S (1978) Chronic recurrent multifocal osteomyelitis and pustulosis palmoplantaris. J Pediatr 93(2):227–231PubMedCrossRefGoogle Scholar
  3. 3.
    Iyer RS, Thapa MM, Chew FS (2011) Chronic recurrent multifocal osteomyelitis: review. AJR Am J Roentgenol 196:87–91CrossRefGoogle Scholar
  4. 4.
    Chamot AM, Benhamou CL, Kahn MF, Beraneck L, Kaplan G, Prost A (1987) Acne-pustulosis-hyperostosis-osteitis syndrome. Results of a national survey. 85 cases. Rev Rhum Mal Osteoartic 54(3):187–196PubMedGoogle Scholar
  5. 5.
    Gikas PD, Islam L, Aston W, Tirabosco R, Saifuddin A, Briggs TW, Cannon SR, O’Donnell P, Jacobs B, Flanagan AM (2009) Nonbacterial osteitis: a clinical, histopathological, and imaging study with a proposal for protocol-based management of patients with this diagnosis. J Orthop Sci 14(5):505–516PubMedCrossRefGoogle Scholar
  6. 6.
    Schedel J, Bach B, Kümmerle-Deschner JB, Kötter I (2011) Autoinflammatory syndromes/ fever syndromes. Hautarzt 62(5):389–401PubMedCrossRefGoogle Scholar
  7. 7.
    Ferguson PJ, El-Shanti HI (2007) Autoinflammatory bone disorders. Curr Opin Rheumatol 19(5):492–498PubMedCrossRefGoogle Scholar
  8. 8.
    Galeazzi M, Gasbarrini G, Ghirardello A, Grandemange S, Hoffman HM, Manna R, Podswiadek M, Punzi L, Sebastiani GD, Touitou I, Doria A (2006) Autoinflammatory syndromes. Clin Exp Rheumatol 24:79–85Google Scholar
  9. 9.
    Jansson A, Renner ED, Ramser J, Mayer A, Haban M, Meindl A, Grote V, Diebold J, Jansson V, Schneider K, Belohradsky BH (2007) Classification of non-bacterial osteitis: retrospective study of clinical, immunological and genetic aspects in 89 patients. Rheumatology 46:154–160 (Oxford)PubMedCrossRefGoogle Scholar
  10. 10.
    Catalano-Pons C, Comte A, Wipff J, Quartier P, Faye A, Gendrel D, Duquesne A, Cimaz R, Job-Deslandre C (2008) Clinical outcome in children with chronic recurrent multifocal osteomyelitis. Rheumatology 47(9):1397–1399 (Oxford)PubMedCrossRefGoogle Scholar
  11. 11.
    Huber AM, Lam PY, Duffy CM, Yeung RS, Ditchfield M, Laxer D, Cole WG, Kerr Graham H, Allen RC, Laxer RM (2002) Chronic recurrent multifocal osteomyelitis: clinical outcomes after more than five years of follow-up. J Pediatr 141(2):198–203PubMedCrossRefGoogle Scholar
  12. 12.
    Coinde E, David L, Cottalorda J, Allard D, Bost M, Lucht F, Stéphan JL (2001) Chronic recurrent multifocal osteomyelitis in children: report of 17 cases. Arch Pediatr 8(6):577–583PubMedCrossRefGoogle Scholar
  13. 13.
    Khanna G, Sato TS, Ferguson P (2009) Imaging of chronic recurrent multifocal osteomyelitis. Radiographics 29(4):1159–1177PubMedCrossRefGoogle Scholar
  14. 14.
    Hospach T, Langendoerfer M, von Kalle T, Maier J, Dannecker GE (2010) Spinal involvement in chronic recurrent multifocal osteomyelitis (CRMO) in childhood and effect of pamidronate. Eur J Pediatr 169(9):1105–1111PubMedCrossRefGoogle Scholar
  15. 15.
    Schultz C, Holterhus PM, Seidel A, Jonas S, Barthel M, Kruse K, Bucsky P (1999) Chronic recurrent multifocal osteomyelitis in children. Pediatr Infect Dis J 18:1008–1013PubMedCrossRefGoogle Scholar
  16. 16.
    King SM, Laxer RM, Manson D, Gold R (1987) Chronic recurrent multifocal osteomyelitis: a noninfectious inflammatory process. Pediatr Infect Dis J 6:907–911PubMedCrossRefGoogle Scholar
  17. 17.
    Jurik AG, Helmig O, Ternowitz T, Møller BN (1988) Chronic recurrent multifocal osteomyelitis: a follow-up study. J Pediatr Orthop 8:49–58PubMedCrossRefGoogle Scholar
  18. 18.
    Paller AS, Pachman L, Rich K, Esterly NB, Gonzalez-Crussi F (1985) Pustulosis palmaris et plantaris: its association with chronic regional multifocal osteomyelitis. J Am Acad Dermatol 12:927–930PubMedCrossRefGoogle Scholar
  19. 19.
    Van Howe RS, Starshak RJ, Chusid MJ (1989) Chronic, recurrent multifocal osteomyelitis. Case report and review of the literature. Clin Pediatr 28(2):54–59 (Phila)CrossRefGoogle Scholar
  20. 20.
    Huaux JP, Esselinckx W, Rombouts JJ, Maldague B, Malghem J, Devogelaer JP, Nagant de Deuxchaisnes C (1988) Pustulotic arthroosteitis and chronic recurrent multifocal osteomyelitis in children: report of three cases. J Rheumatol 15:95–100PubMedGoogle Scholar
  21. 21.
    Bousvaros A, Marcon M, Treem W, Waters P, Issenman R, Couper R, Burnell R, Rosenberg A, Rabinovich E, Kirschner BS (1999) Chronic recurrent multifocal osteomyelitis associated with chronic inflammatory bowel disease in children. Dig Dis Sci 44:2500–2507PubMedCrossRefGoogle Scholar
  22. 22.
    Carpenter E, Jackson MA, Friesen CA, Scarbrough M, Roberts CC (2004) Crohn’s-associated chronic recurrent multifocal osteomyelitis responsive to infliximab. J Pediatr 144(4):541–544PubMedCrossRefGoogle Scholar
  23. 23.
    Bognar M, Blake W, Agudelo C (1998) Chronic recurrent multifocal osteomyelitis associated with Crohn’s disease. Am J Med Sci 315:133–135PubMedCrossRefGoogle Scholar
  24. 24.
    Schilling F, Märker-Hermann E (2003) Chronic recurrent multifocal osteomyelitis in association with chronic inflammatory bowel disease: entheropathic CRMO. Z Rheumatol 62(6):527–538PubMedCrossRefGoogle Scholar
  25. 25.
    Bazrafshan A, Zanjani KS (2000) Chronic recurrent multifocal osteomyelitis associated with ulcerative colitis: a case report. J Pediatr Surg 35:1520–1522PubMedCrossRefGoogle Scholar
  26. 26.
    Carr AJ, Cole WG, Robertston DM, Chow CW (1993) Chronic multifocal osteomyelitis. J Bone Joint Surg Br 75:582–591PubMedGoogle Scholar
  27. 27.
    Wipff J, Adamsbaum C, Kahan A, Job-Deslandre C (2011) Chronic recurrent multifocal osteomyelitis. Joint Bone Spine 78(6):555–560Google Scholar
  28. 28.
    Job-Deslandre C, Krebs S, Kahan A (2001) Chronic recurrent multifocal osteomyelitis: five-year outcomes in 14 pediatric cases. Joint Bone Spine 68:245–251PubMedCrossRefGoogle Scholar
  29. 29.
    Girschick HJ, Krauspe R, Tschammler A, Huppertz HI (1998) 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 157:28–33PubMedCrossRefGoogle Scholar
  30. 30.
    Fritz J, Tzaribatchev N, Claussen CD, Carrino JA, Horger MS (2009) Chronic recurrent multifocal osteomyelitis: comparison of whole-body MR imaging with radiography and correlation with clinical and laboratory data. Radiology 252(3):842–851PubMedCrossRefGoogle Scholar
  31. 31.
    Bjorkstén B, Boquist L (1980) J Histopathological aspects of chronic recurrent multifocal osteomyelitis. Bone Joint Surg Br 62(3):376–380Google Scholar
  32. 32.
    Probst FP, Bjorksten B, Gustavson K-H (1978) Radiological aspect of chronic recurrent multifocal osteomyelitis. Ann Radiol 21:115–112 (Paris)PubMedGoogle Scholar
  33. 33.
    Chow LT, Griffith JF, Kumta SM, Leung PC (1999) Chronic recurrent multifocal osteomyelitis: a great clinical and radiologic mimic in need of recognition by the pathologist. APMIS 107(4):369–379PubMedCrossRefGoogle Scholar
  34. 34.
    Girschick HJ, Huppertz HI, Harmsen D, Krauspe R, Müller-Hermelink HK, Papadopoulos T (1999) Chronic recurrent multifocal osteomyelitis in children: diagnostic value of histopathology and microbial testing. Hum Pathol 30(1):59–65PubMedCrossRefGoogle Scholar
  35. 35.
    Mortensson W, Edeburn G, Fries M, Nilsson R (1988) Chronic recurrent multifocal osteomyelitis in children. A roentgenologic and scintigraphic investigation. Acta Radiol 29(5):565–570PubMedGoogle Scholar
  36. 36.
    Yu L, Kasser JR, O’Rourke E, Kozakewich H (1989) Chronic recurrent multifocal osteomyelitis. Association with vertebra plana. J Bone Joint Surg Am 71:105–112PubMedGoogle Scholar
  37. 37.
    Duffy CM, Lam PY, Ditchfield M, Allen R, Graham HK (2002) Chronic recurrent multifocal osteomyelitis: review of orthopaedic complications at maturity. J Pediatr Orthop 22(4):501–505PubMedGoogle Scholar
  38. 38.
    Manson D, Wilmot DM, King S, Laxer RM (1989) Physeal involvement in chronic recurrent multifocal osteomyelitis. Pediatr Radiol 20:76–79PubMedCrossRefGoogle Scholar
  39. 39.
    Miettunen PM, Wei X, Kaura D, Reslan WA, Aguirre AN, Kellner JD (2009) Dramatic pain relief and resolution of bone inflammation following pamidronate in 9 pediatric patients with persistent chronic recurrent multifocal osteomyelitis (CRMO). Pediatr Rheumatol Online J 7:2PubMedCrossRefGoogle Scholar
  40. 40.
    Chiu CK, Singh VA (2009) Chronic recurrent multifocal osteomyelitis of the first metatarsal bone: a case report. J Orthop Surg 17(1):119–122 (Hong Kong)Google Scholar
  41. 41.
    Abril JC, Ramirez A (2007) Successful treatment of chronic recurrent multifocal osteomyelitis with indomethacin: a preliminary report of five cases. J Pediatr Orthop 27(5):587–591PubMedCrossRefGoogle Scholar
  42. 42.
    Girschick HJ, Raab P, Surbaum S, Trusen A, Kirschner S, Schneider P et al (2005) Chronic non-bacterial osteomyelitis in children. Ann Rheum Dis 64:279–285PubMedCrossRefGoogle Scholar
  43. 43.
    Handrick W, Hormann D, Voppmann A, Schille R, Reichardt P, Trobs RB et al (1998) Chronic recurrent multifocal osteomyelitis—report of eight patients. Pediatr Surg Int 14:195–198PubMedGoogle Scholar
  44. 44.
    Holden W, David J (2005) Chronic recurrent multifocal osteomyelitis: two cases of sacral disease responsive to corticosteroids. Clin Infect Dis 40:616–619PubMedCrossRefGoogle Scholar
  45. 45.
    Ishikawa-Nakayama K, Sugiyama E, Sawazaki S, Taki H, Kobayashi M, Koizumi F, Furuta I (2000) Chronic recurrent multifocal osteomyelitis showing marked improvement with corticosteroid treatment. J Rheumatol 27:1318–1319PubMedGoogle Scholar
  46. 46.
    Simm PJ, Allen RC, Zacharin MR (2008) Bisphosphonate treatment in chronic recurrent multifocal osteomyelitis. J Pediatr 152(4):571–575PubMedCrossRefGoogle Scholar
  47. 47.
    Compeyrot-Lacassagne S, Rosenberg AM, Babyn P, Laxer RM (2007) Pamidronate treatment of chronic noninfectious inflammatory lesions of the mandible in children. J Rheumatol 34(7):1585–1589PubMedGoogle Scholar
  48. 48.
    Yamazaki Y, Satoh C, Ishikawa M, Notani K, Nomura K, Kitagawa Y (2007) Remarkable response of juvenile diffuse sclerosing osteomyelitis of mandible to pamidronate. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104(1):67–71PubMedCrossRefGoogle Scholar
  49. 49.
    Gleeson H, Wiltshire E, Briody J, Hall J, Chaitow J, Sillence D, Cowell C, Munns C (2008) Childhood chronic recurrent multifocal osteomyelitis: pamidronate therapy decreases pain and improves vertebral shape. J Rheumatol 35(4):707–712PubMedGoogle Scholar
  50. 50.
    Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R (1998) Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 339(14):947–952PubMedCrossRefGoogle Scholar
  51. 51.
    De Cunto A, Maschio M, Lepore L, Zennaro F (2009) A case of chronic recurrent multifocal osteomyelitis successfully treated with neridronate. J Pediatr 154(1):154–155PubMedGoogle Scholar
  52. 52.
    Rogers MJ, Gordon S, Benford HL et al (2000) Cellular and molecular mechanisms of action of bisphosphonates. Cancer 88(12 Suppl): 2961–2978PubMedCrossRefGoogle Scholar
  53. 53.
    Toussirot E, Wendling D (2007) Antiinflammatory treatment with bisphosphonates in ankylosing spondylitis. Curr Opin Rheumatol 19(4):340–345PubMedCrossRefGoogle Scholar
  54. 54.
    Dicuonzo G, Vincenzi B, Santini D, Avvisati G, Rocci L, Battistoni F, Gavasci M, Borzomati D, Coppola R, Tonini G (2003) Fever after zoledronic acid administration is due to increase in TNF-alpha and IL-6. J Interferon Cytokine Res 23(11):649–654PubMedCrossRefGoogle Scholar
  55. 55.
    Hewitt RE, Lissina A, Green AE, Slay ES, Price DA, Sewell AK (2005) The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins. Clin Exp Immunol 139(1):101–111PubMedCrossRefGoogle Scholar
  56. 56.
    Gallacher SJ, Ralston SH, Patel U, Boyle IT (1989) Side-effects of pamidronate. Lancet 2:42–43PubMedCrossRefGoogle Scholar
  57. 57.
    Adami S, Bhalla AK, Dorizzi R, Montesanti F, Rosini S, Salvagno G, Lo Cascio V (1987) The acute-phase response after bisphosphonate administration. Calcif Tissue Int 41:326–331PubMedCrossRefGoogle Scholar
  58. 58.
    Gallagher KT, Roberts RL, MacFarlane JA, Stiehm ER (1997) Treatment of chronic recurrent multifocal osteomyelitis with interferon gamma. J Pediatr 131(3):470–472PubMedCrossRefGoogle Scholar
  59. 59.
    Andersson R (1995) Effective treatment with interferon-alpha in chronic recurrent multifocal osteomyelitis. J Interferon Cytokine Res 15(10):837–838PubMedCrossRefGoogle Scholar
  60. 60.
    Marangoni RG, Halpern AS (2010) Chronic recurrent multifocal osteomyelitis primarily affecting the spine treated with anti-TNF therapy. Spine (Phila Pa 1976) 35(7):E253–256Google Scholar
  61. 61.
    Eleftheriou D, Gerschman T, Sebire N, Woo P, Pilkington CA, Brogan PA (2010) Biologic therapy in refractory chronic non-bacterial osteomyelitis of childhood. Rheumatology 49(8):1505–1512 (Oxford)PubMedCrossRefGoogle Scholar
  62. 62.
    Deutschmann A, Mache CJ, Bodo K, Zebedin D, Ring E (2005) Successful treatment of chronic recurrent multifocal osteomyelitis with tumor necrosis factor-alpha blockage. Pediatrics 116(5):1231–1233PubMedCrossRefGoogle Scholar
  63. 63.
    Eisenstein EM, Syverson GD, Vora SS, Williams CB (2011) Combination therapy with methotrexate and etanercept for refractory chronic recurrent multifocal osteomyelitis. J Rheumatol 38(4):782–783PubMedCrossRefGoogle Scholar
  64. 64.
    Hentunen TA, Choi SJ, Boyce BF, Dallas MR, Dallas SL, Shen-Ong GL, Roodman GD (2000) A murine model of inflammatory bone disease. Bone 26:183–188PubMedCrossRefGoogle Scholar
  65. 65.
    Wagner AD, Andresen J, Jendro MC, Hulsemann JL, Zeidler H (2002) Sustained response to tumor necrosis factor alpha-blocking agents in two patients with SAPHO syndrome. Arthritis Rheum 46:1965–1968PubMedCrossRefGoogle Scholar
  66. 66.
    Hurtado-Nedelec M, Chollet-Martin S, Nicaise-Roland P, Grootenboer-Mignot S, Ruimy R, Meyer O, Hayem G (2008) Characterization of the immune response in the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Rheumatology 47:1160–1167PubMedCrossRefGoogle Scholar
  67. 67.
    Olivieri I, Padula A, Ciancio G, Salvarani C, Niccoli L, Cantini F (2002) Successful treatment of SAPHO syndrome with infliximab: report of two cases. Ann Rheum Dis 61:375–376PubMedCrossRefGoogle Scholar
  68. 68.
    Widmer M, Weishaupt D, Brühlmann P, Michel BA, Forster A (2003) Infliximab in the treatment of SAPHO syndrome: clinical experience and MRI response (Abstract). Ann Rheum Dis 62(Suppl. I):250–251Google Scholar
  69. 69.
    Asmussen KH (2003) Successful treatment of SAPHO syndrome with infliximab. A case report. Arthritis Rheum 48(Suppl.1):S621Google Scholar
  70. 70.
    Kyriazis NC, Tachoula AV, Sfontouris CI (2004) Successful treatment of refractory SAPHO syndrome with infliximab. Ann Rheum Dis 63(Suppl. I):388–389Google Scholar
  71. 71.
    Golla A, Jansson A, Ramser J, Hellebrand H, Zahn R, Meitinger T, Belohradsky BH, Meindl A (2002) Chronic recurrent multifocal osteomyelitis (CRMO): evidence for a susceptibility gene located on chromosome 18q21.3–18q22. Eur J Hum Genet 10(3):217–221PubMedCrossRefGoogle Scholar
  72. 72.
    Byrd L, Grossmann M, Potter M, Shen-Ong GL (1991) Chronic multifocal osteomyelitis, a new recessive mutation on chromosome 18 of the mouse. Genomics 11(4):794–798PubMedCrossRefGoogle Scholar
  73. 73.
    Hughes AE, Shearman AM, Weber JL, Barr RJ, Wallace RG, Osterberg PH, Nevin NC, Mollan RA (1994) Genetic linkage of familial expansile osteolysis to chromosome 18q. Hum Mol Genet 3:359–361PubMedCrossRefGoogle Scholar
  74. 74.
    Cody JD, Singer FR, Roodman GD, Otterund B, Lewis TB, Leppert M, Leach RJ (1997) Genetic linkage of Paget disease of the bone to chromosome 18q. Am J Hum Genet 61:1117–1123PubMedCrossRefGoogle Scholar
  75. 75.
    Ferguson PJ, Bing X, Vasef MA, Ochoa LA, Mahgoub A, Waldschmidt TJ, Tygrett LT, Schlueter AJ, El-Shanti H (2006) A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis. Bone 38(1):41–47PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Bristol Royal Hospital for ChildrenBristolUK
  2. 2.Royal National Hospital for Rheumatic DiseasesBathUK

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