title: Multifocal osteomyelitis caused by nontuberculous mycobacteria in patients with a genetic defect of the interferon-gamma receptor.
abstract: We describe three patients with multifocal osteomyelitis caused by Mycobacterium avium and a family history of one or more first degree family members diagnosed with various clinical presentations of infections with nontuberculous mycobacteria. There was a significant delay in the diagnosis and they had a protracted course of their illness, which responded only slowly to prolonged multi-drug treatment. In one patient, additional treatment with interferon-gamma (IFN-gamma) was necessary. Macrophages of these patients had decreased in vitro responsiveness to IFN-gamma. Genomic sequencing revealed that these patients and their affected family members were heterozygous for a previously described dominant negative mutation in the gene encoding the IFN-gamma binding receptor-1 chain. The clinical presentations of the infections with nontuberculous mycobacteria in these families, with spread limited to skin, bone and lymph nodes, is discussed in the light of the immune mechanisms that are responsible for the clearance of otherwise poorly pathogenic environmental mycobacteria.
authors.affiliation: Department of Infectious Diseases, C5P, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: S M
authors.initials: SM
authors.lastname: Arend
authors.forename: R
authors.initials: R
authors.lastname: Janssen
authors.forename: J J
authors.initials: JJ
authors.lastname: Gosen
authors.forename: H
authors.initials: H
authors.lastname: Waanders
authors.forename: T
authors.initials: T
authors.lastname: de Boer
authors.forename: T H
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: J T
authors.initials: JT
authors.lastname: van Dissel
mesh_terms: D000328:Adult; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D015270:Mycobacterium avium-intracellulare Infection / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology*; D010019:Osteomyelitis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology*; D010375:Pedigree; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics* / Q000627:therapeutic use; D013997:Time Factors; D000096743:Interferon gamma Receptor
chemical_list: D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor