Anti-tumor necrosis factor treatment in cherubism--clinical, radiological and histological findings in two children.
Bone
; 52(1): 347-53, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23069372
ABSTRACT
Cherubism is a rare and disfiguring genetic disorder with excessive bone resorption and multilocular lesions in the mandible and/or maxilla. The disease-causing gain-of-function mutations in the SH3-binding protein 2 (SH3BP2) gene result in increased myeloid cell responses to macrophage colony stimulating factor and RANK ligand, formation of hyperactive osteoclasts (giant cells), and hyper-reactive macrophages that produce excessive amounts of the inflammatory cytokine tumor necrosis factor α (TNF-α). Recent findings in the cherubism mouse model suggest that TNF-α plays a major role in disease pathogenesis and that removal of TNF-α prevents development of the bone phenotype. We treated two children with cherubism with the TNF-α antagonist adalimumab for approximately 2.5 years and collected extensive clinical, radiological and histological follow-up data during the treatment. Histologically the treatment resulted in a significant reduction in the number of multinucleated giant cells and TNF-α staining positivity in both patients. As evaluated by computed tomography and magnetic resonance imaging, the lesions in Patient 1 showed either moderate enlargement (mandibular symphysis) or remained stable (mandibular rami and body, the maxilla). In Patient 2, the lesions in mandibular symphysis showed enlargement during the first 8 months of treatment, and thereafter the lesions remained unchanged. Bone formation and resorption markers remained unaffected. The treatment was well tolerated. Based on our findings, TNF-α antagonist may decrease the formation of pathogenic giant cells, but does not result in lesion regression or prevent lesion expansion in active cherubism. TNF-α modulator treatment thus does not appear to provide sufficient amelioration for patients suffering from cherubism.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Querubismo
/
Fator de Necrose Tumoral alfa
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Bone
Ano de publicação:
2013
Tipo de documento:
Article