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Titre

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 Abstract
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.

Keywords
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. as the "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 Definition
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 Differential diagnosis
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. Clinical manifestations
Skeletal manifestations

Disease course
• 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 Treatment
Non steroid anti-inflammatory drugs (NSAID) are Therapeutically, antibiotic treatment is considered to be ineffective and treatment with Etiology
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 References
microbial techniques no apparent infectious 1. 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 2. Mollan, R.A., B.F. Craig, and J.D. Biggart.
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Diagnosis
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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. 27. Tan, B.S., V. Nayanar, R. Mansberg, I.P.
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