Chronic recurrent multifocal osteomyelitis - A concise review and genetic update
ABSTRACT Chronic recurrent multifocal osteomyelitis is an autoinflammatory disorder characterized by bone pain and fever, a course of exacerbations and remissions, and a frequent association with other inflammatory conditions. Because its etiology is largely unknown, the diagnosis is still based on clinical criteria; treatment is empiric and not always successful. The diagnosis is supported by the presence of osteolytic lesions with surrounding sclerosis apparent on radiographs, and silent asymptomatic lesions frequently appear on nuclear scans. The histologic findings in bone biopsies are nonspecific, showing inflammatory changes with granulocytic infiltration. Several observations suggest the contribution of genetic factors to the etiology of chronic recurrent multifocal osteomyelitis. Indeed, mutations in LPIN2 cause a syndromic form of chronic recurrent multifocal osteomyelitis known as Majeed syndrome, while mutations in pstpip2 cause a murine form of the disorder. The roles played by LPIN2 and the human homolog of pstpip2, PSTPIP2, in the etiology of chronic recurrent multifocal osteomyelitis are uncertain but are currently being investigated. We emphasize the need to validate diagnostic clinical criteria and develop new pathogenesis-based targeted therapy.
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ABSTRACT: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, systemic, aseptic, inflammatory disorder that involves different sites. Pathogenesis of chronic recurrent multifocal osteomyelitis is currently unknown. To our knowledge, there are no reports of CRMO from Saudi Arabia. We describe the clinical and laboratory features and treatment of a cohort of children with CRMO. Retrospective, patients referred to pediatric rheumatology clinic at a tertiary care center in Riyadh, Saudi Arabia. The diagnosis of CRMO was based on evidence of recurrent osteomyelitis with radiographic evidence of chronic osteomyelitis involving at least two sites in the absence of infectious cause in a child less than 14 years old. Ten patients (9 female, 1 male) with CRMO; 2 patients presented in infancy. The referral diagnosis was inaccurate in all patients. All of them presented with pain and 8 of them had associated swelling and were found to have multifocal lesions. Imaging studies showed findings consistent with chronic osteomyelitis. Histopathological and microbiological examination confirmed the diagnosis in 9 patients. Cyclic pamidronate infusions induced good improvement in 6 patients. This report indicates that CRMO may be overlooked in our community. Early diagnosis and treatment are required to avoid potential complications.Annals of Saudi medicine 11/2012; 32(6):611-4. DOI:10.5144/0256-4947.2012.611 · 0.71 Impact Factor
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ABSTRACT: To provide an update on the genetics and immunologic basis of autoinflammatory bone disorders including chronic recurrent multifocal osteomyelitis including the monogenic forms of the disease. Ongoing research in murine, canine and human models of sterile bone inflammation has solidified the hypothesis that sterile bone inflammation can be genetically driven. Mutations in Pstpip2, LPIN2 and IL1RN have been identified in monogenic autoinflammatory bone disorders that have allowed more detailed dissection of the immunologic defects that can produce sterile osteomyelitis. Recent studies in murine chronic multifocal osteomyelitis, deficiency of the interleukin-1 receptor antagonist (DIRA), Majeed syndrome and SAPHO syndrome reveal abnormalities in innate immune system function. IL-1 pathway dysregulation is present in several of these disorders and blocking IL-1 therapeutically has resulted in control of disease in DIRA, Majeed syndrome and in some cases of SAPHO and CRMO. Basic research demonstrates the importance of the innate immune system in disease pathogenesis and offers clues about potential disease triggers. Research and clinical data produced over the last several years support the important role of innate immunity in sterile osteomyelitis. Based on what has been learned in the monogenic autoinflammatory bone disorders, IL-1 is emerging as an important pathway in the development of sterile bone inflammation.Current opinion in rheumatology 09/2013; 25(5):658-64. DOI:10.1097/BOR.0b013e328363eb08 · 5.07 Impact Factor
- Infectious Disease in Clinical Practice 01/2014; DOI:10.1097/IPC.0000000000000152