Chronic Recurrent Multifocal Osteomyelitis (CRMO)

Abstract

Chronic recurrent multifocal osteomyelitis is an autoinflammatory disease that has a genetic component to disease susceptibility. It is a painful disease in which osteomyelitis occurs in one or more sites. Cultures are sterile and there is typically no improvement with antibiotics. It is associated with a personal or family history of inflammatory disease of the intestine, joints, or skin, most commonly psoriasis or Crohn’s disease. Adults can develop sterile osteomyelitis as part of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. CRMO can occur as part of a Mendelian syndrome; however, the vast majority of cases of CRMO and SAPHO syndrome are non-syndromic. Four genes have been identified that when mutated can cause sterile bone inflammation. Mutations in LPIN2, IL1RN, and FBLIM1 have been identified in humans with CRMO and Pstpip2 in a murine model of CRMO. The inflammatory bone disease in the chronic multifocal osteomyelitis (cmo) mouse is IL-1β dependent and neutrophil driven. Syndromic forms of human CRMO are also IL-1 driven, but the role of IL-1 in non-syndromic cases is not clear. Diet-driven changes in the microbiome may play a key role in disease development in murine cmo, as a high-fat diet is associated with dysbiosis and prevents disease manifestations. Fecal transplants from high-fat diet-fed cmo mice can modulate the cmo phenotype. Neutrophils from the mice fed a high-fat diet produced less IL-1β again supporting the role of the neutrophil in cmo disease pathogenesis. The role of the microbiota in human CRMO and SAPHO syndrome is unknown.