Do you want to buy antibiotics online without prescription? http://buyantibiotics24h.com/ - This is pharmacy online for you!
Chronic recurrent multifocal osteomyelitis in children
Author: Doctor Hermann Girschick1
Creation Date: March 2002
Scientific Editor: Doctor Frank Dressler
1Klinik für Kinderkardiologie, Universitätsklinik der RWTH Aachen - Institut für Humangenetik, Pauwelsstr. 30, 52074 Aachen, German
Included diseases Differential diagnosis Frequency Clinical signs Etiology Diagnostic methods Treatment References
Chronic recurrent multifocal osteomyelitis (CRMO) in children is an inflammatory disorder. It affects mainly
the metaphyses of the long bones, in addition to the spine, the pelvis and the shoulder girdle. However,
bone lesions can occur at any site of the skeleton. Even though this disease has been recognized as a
clinical entity for almost three decades now, its origin and pathogenesis are not entirely clear. No
apparent infectious agents are detectable at the site of the bone lesion. No epidemiological data on
incidence and prevalence have been published so far. However, incidence might be something around
1:1,000,000, thus reflecting the number of patients followed-up. Clinical diagnosis in an affected child can
be difficult because the clinical picture and course of disease may vary significantly. It has been shown
that histological examination alone does not allow the distinction of CRMO from acute or subacute
bacterial osteomyelitis. Therefore an extensive microbial workup of the tissue biopsy, including PCR-
techniques, is essential in order to establish the diagnosis and decide as to the treatment. Non steroid
anti-inflammatory drugs (NSAID) are the treatment of choice. In case of frequent relapses oral steroid
treatment, bisphosphonates and azulfidine have been used and are reported to be beneficial.
Multifocal osteomyelitis, enthesitis related arthritis, psoriasis arthritis, palmoplantar pustulosis
Disease name and synonyms
unifocal osteolytic lesions in children with no
In previous reports a multitude of labels have
apparent infectious agent detectable at the site
of the bone lesion into the diagnosis (13-18). In
multifocal osteomyelitis (CRMO): "chronic
sclerosing osteomyelitis" (2), "condensing
"SAPHO-syndrome" (Synovitis, Acne,
osteitis" (3, 4), "sclerosis and hyperostosis" (5-
Pustulosis, Hyperostosis, Osteitis) (19, 20).
7), "primary chronic osteomyelitis" (8) and
CRMO has been regarded by Kahn et al.
"pustulotic arthroosteitis" (9, 10). Descriptive
histopathological terms have also been used to
(21,22). Histologically, bone lesions in uni- and
plasmacellular osteomyelitis" (11, 12). Even
though the denomination includes "multiple" and "recurrent", some authors include non-relapsing
Girschick H. Chronic recurrent multifocal osteomyelitis in children.Orphanet encyclopedia, March 2002. http://www.orpha.net/data/patho/GB/uk-CRMO.pdf 1
Histologically, bone lesions in uni- and multifocal
Chronic recurrent multifocal osteomyelitis
CRMO, as well as SAPHO show similar features
(CRMO) in children is an inflammatory disorder.
(6, 13, 23-26). Depending on disease course
It mainly affects the metaphyses of the long
biopsy may show subperiosteal bone formation
bones, in addition to the spine, the pelvis and the
which is a sign of chronic inflammation with
shoulder girdle. However, bone lesions can
infiltration of leukocytes. In very early lesions
granulocytes can be observed, and later on mainly lymphocytes or monocytes. Later stages
show fibrotic changes (13). Histological
examination alone does not allow distinction of
osteomyelitis (13, 26). Therefore extensive
microbial workup of the tissue biopsy, including
PCR-techniques, is essential in order to
establish the diagnosis and decide about treatment.
• Unifocal or multifocal, initially osteolytic, later
Recently, evolvement of CRMO into enthesitis-
hyperostotic and sclerotic lesions mainly in
related arthritis or spondyloarthropathy has been
documented in three cohorts of children and
young adults (18, 31, 34). Inflammatory joint
affected. Relapses are frequent even under
involvement already at the time of diagnosis and
during the course of the disease might have
• Arthritis of adjacent and distal joints is
Pathogenetically, CRMO is linked to juvenile
enthesitis-related arthritis at onset or during
arthritis and features of CRMO can overlap
features of enthesitis-related arthritis or psoriatic arthritis.
Other organ involvement
• Palmoplantar pustulosis, psoriasis or acne
Non steroid anti-inflammatory drugs (NSAID) are
Therapeutically, antibiotic treatment is considered to be ineffective and treatment with
non steroidal anti-inflammatory agents has been
Pathogenetically CRMO is linked to enthesitis-
reported to be effective repetitively (13, 24, 27-
related arthritis and psoriatic arthritis. There has
32). In patients with frequent relapses oral
been an intense discussion on the putative
steroid treatment (31, 33, 34), bisphosphonates
(35, 36) and sulfasalazine (31, 34) have been
Propionibacterium acnes has been postulated to
used and were reported to be beneficial.
be involved in the pathogenesis. However, in larger cohorts and by using state of the art
microbial techniques no apparent infectious
. Giedion, A., W. Holthusen, L.F. Masel, and D.
agents could be detected at the site of the bone
lesion in pediatric patients. Even though this
"symmetrical" osteomyelitis]. Ann Radiol (Paris)
disease has been recognized as a clinical entity
for almost three decades now (1), its origin and
. Mollan, R.A., B.F. Craig, and J.D. Biggart.
1984. Chronic sclerosing osteomyelitis. An unusual case. J Bone Joint Surg Br 66, no.
Incidence and prevalence
No epidemiological data on incidence and
. Lissens, M., F. Bruyninckx, and N. Rosselle.
1990. Condensing osteitis of the clavicle. Report
However, incidence might be estimated at
of two cases and review of the literature. Acta
Belg Med Phys 13, no. 4:235-40. 4
. Appell, R.G., H.C. Oppermann, W. Becker, R.
Kratzat, W.E. Brandeis, and E. Willich. 1983.
Clinical diagnosis in affected children can be
Condensing osteitis of the clavicle in childhood:
difficult because the clinical picture and course
a rare sclerotic bone lesion. Review of literature
and report of seven patients. Pediatr Radiol 13, no. 6:301-6.
Girschick H. Chronic recurrent multifocal osteomyelitis in children.Orphanet encyclopedia, March 2002. http://www.orpha.net/data/patho/GB/uk-CRMO.pdf 2
. Jurik, A.G., and B.N. Moller. 1987. Chronic
osteitis toward spondylarthropathy over the long
sclerosing osteomyelitis of the clavicle. A
manifestation of chronic recurrent multifocal
. Kahn, M.F., M. Bouvier, E. Palazzo, J.G.
osteomyelitis. Arch Orthop Trauma Surg 106,
Tebib, and F. Colson. 1991. Sternoclavicular
pustulotic osteitis (SAPHO). 20-year interval
. Jurik, A.G., and B.N. Moller. 1986.
between skin and bone lesions. J Rheumatol 18,
Inflammatory hyperostosis and sclerosis of the
clavicle. Skeletal Radiol 15, no. 4:284-90.
. Kahn, M.F., and A.M. Chamot. 1992.
. Jurik, A.G., B.N. Moller, M.K. Jensen, J.T.
Jensen, and H. Graudal. 1986. Sclerosis and
. Kahn, M.F. 1993. Psoriatic arthritis and
synovitis, acne, pustulosis, hyperostosis, and
. Jani, L., and W. Remagen. 1983. Primary
osteitis syndrome. Curr Opin Rheumatol 5, no.
chronic osteomyelitis. Int Orthop 7, no. 2:79-83.
. Huaux, J.P., W. Esselinckx, H. Meunier, J.
. Chamot, A.M., C.L. Benhamou, M.F. Kahn,
L. Beraneck, G. Kaplan, and A. Prost. 1987.
Deuxchaisnes. 1987. Pustulotic arthro-osteitis in
children and adults. A report of 13 cases. Clin
Results of a national survey. 85 cases]. Rev
. Huaux, J.P., W. Esselinckx, J.J. Rombouts,
. Carr, A.J., W.G. Cole, D.M. Roberton, and
B. Maldague, J. Malghem, J.P. Devogelaer, and
C. Nagant de Deuxchaisnes. 1988. Pustulotic
osteomyelitis. J Bone Joint Surg Br 75, no.
arthroosteitis and chronic recurrent multifocal
osteomyelitis in children. Report of three cases.
. Björksten, B., and L. Boquist. 1980.
Histopathological aspects of chronic recurrent
. Krauspe, R., H. Girschick, and H.I. Huppertz.
multifocal osteomyelitis. J Bone Joint Surg Br 62,
1997. [Lymphoplasmacellular osteomyelitis].
. Yu, L., J.R. Kasser, E. O'Rourke, and H.
. Trobs, R., R. Moritz, U. Buhligen, J. Bennek,
Kozakewich. 1989. Chronic recurrent multifocal
W. Handrick, D. Hormann, and T. Meier. 1999.
osteomyelitis. Association with vertebra plana. J
Changing pattern of osteomyelitis in infants and
children. Pediatr Surg Int 15, no. 5-6:363-72.
. Reith, J.D., T.W. Bauer, and J.P. Schils.
. Girschick, H.J., H.I. Huppertz, D. Harmsen,
R. Krauspe, H.K. Muller-Hermelink, and T.
(synovitis, acne, pustulosis, hyperostosis,
osteitis) syndrome. Am J Surg Pathol 20, no.
multifocal osteomyelitis in children: diagnostic
value of histopathology and microbial testing.
. Tan, B.S., V. Nayanar, R. Mansberg, I.P.
Murray, and M.A. Rossleigh. 1996. Two cases of
. Weihe, S., H. Eufinger, O. Terhaar, M.
chronic recurrent multifocal osteomyelitis:
Konig, and E. Machtens. 2000. [Mandibular
radiological and scintigraphic findings. Australas
involvement in chronic recurrent multifocal
osteomyelitis (CRMO) in adulthood]. Mund
. Sundaram, M., D. McDonald, E. Engel, M.
Rotman, and E.C. Siegfried. 1996. Chronic
. Schilling, F., A. Eckardt, and S. Kessler.
recurrent multifocal osteomyelitis: an evolving
clinical and radiological spectrum. Skeletal
osteomyelitis]. Z Orthop Ihre Grenzgeb 138, no.
. Van Howe, R.S., R.J. Starshak, and M.J.
. Schilling, F., and S. Kessler. 2001. [Chronic
Chusid. 1989. Chronic, recurrent multifocal
recurrent multifocal osteomyelitis-- I. Review].
osteomyelitis. Case report and review of the
literature. Clin Pediatr (Phila) 28, no. 2:54-9.
. Roldan, J.C., H. Terheyden, A. Dunsche,
. Handrick, W., D. Hormann, A. Voppmann, R.
W.U. Kampen, and J.O. Schroeder. 2001. Acne
Schille, P. Reichardt, R.B. Trobs, R.P. Moritz,
with chronic recurrent multifocal osteomyelitis
and M. Borte. 1998. Chronic recurrent multifocal
involving the mandible as part of the SAPHO
osteomyelitis--report of eight patients. Pediatr
syndrome: case report. Br J Oral Maxillofac Surg
. Job-Deslandre, C., S. Krebs, and A. Kahan.
. Vittecoq, O., L.A. Said, C. Michot, O. Mejjad,
2001. Chronic recurrent multifocal osteomyelitis:
J.M. Thomine, P. Mitrofanoff, J. Lechevallier, P.
five-year outcomes in 14 pediatric cases. Joint
Ledosseur, A. Gayet, P. Lauret, and X. le Loet.
2000. Evolution of chronic recurrent multifocal
Girschick H. Chronic recurrent multifocal osteomyelitis in children.Orphanet encyclopedia, March 2002. http://www.orpha.net/data/patho/GB/uk-CRMO.pdf 3
. Schuster, T., J. Bielek, H.G. Dietz, and B.H.
long term follow up and treatment of relapses.
Belohradsky. 1996. Chronic recurrent multifocal
osteomyelitis (CRMO). Eur J Pediatr Surg 6, no.
. Schilling, F., W. Coerdt, A. Eckardt, H. Full,
T. Hospach, S. Kessler, M. Kocher, and K.F.
. Pelkonen, P., S. Ryoppy, J. Jaaskelainen, J.
Kreitner. 2001. [Pelvic type of chronic recurrent
Rapola, H. Repo, and I. Kaitila. 1988. Chronic
multifocal osteomyelitis]. Klin Padiatr 213, no.
osteomyelitislike disease with negative bacterial
cultures. Am J Dis Child 142, no. 11:1167-73.
. Akikusa, J.D., M. Zacharin, A.W. Shugg, and
. Girschick, H.J., P. Raab, S. Kirschner, S.
R.C. Allen. 2001. Bisphosphonates in the
treatment of chronic recurrent multifocal
recurrent multifocal osteomyelitis in children:
osteomyelitis. Arthritis Rheum 44, no. 9 (Suppl):171.
Girschick H. Chronic recurrent multifocal osteomyelitis in children.Orphanet encyclopedia, March 2002. http://www.orpha.net/data/patho/GB/uk-CRMO.pdf 4
“I was about 50 meters away when it blew up. The blast knocked me off my feet and into the side of a Humvee. I must have blacked out for a minute or two, but when I came to there was nothing left of the vehicle. No remnants; just char and a crater.” When 28-year-old Christopher Harmon was discharged on May 26,2006, after eight years in the Marine Corps, he had a chestful of dec-oration
Unaware of Deep issues Excavations 24-year-old are this months worker killed in Newsletter Kent trench headline arising collapse from news headlines and onsite reports. not forgetting checks manslaughter after a introduced. Support Police and the air am-vations. Such as lack and other equipment bulance were called of planning , support shall be pres