Chronic Recurrent Multifocal Osteomyelitis (CRMO): Presentation, Pathogenesis, and Treatment

Abstract

Purpose of ReviewChronic non-bacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder. We summarize the clinical presentation, diagnostic approaches, most recent advances in understanding the pathophysiology, and available treatment options and outcomes in CNO/CRMO.Recent FindingsThough the exact molecular pathophysiology of CNO/CRMO remains somewhat elusive, it appears likely that variable defects in the TLR4/MAPK/inflammasome signaling cascade result in an imbalance between pro- and anti-inflammatory cytokine expressions in monocytes from CNO/CRMO patients. In this context, we present previously unpublished data on cytokine and chemokine expression in monocytes and tissues.SummaryCNO/CRMO is an autoinflammatory bone disorder resulting from imbalanced cytokine expression from innate immune cells. Though the exact molecular pathophysiology remains unclear, variable molecular defects appear to result in inflammasome activation and pro-inflammatory cytokine expression in monocytes from CNO/CRMO patients. Recent advances suggest signaling pathways and single molecules as biomarkers for CNO/CRMO as well as future treatment targets.

Use of infliximab in patient with chronic non-bacterial osteomyelitis, case report

“…There are descriptions of association with other inflammatory diseases, such as Crhon's disease, palmoplantar pustulosis, psoriasis, Sweet's syndrome, among others [9]. Nonsteroidal anti-inflammatory and bisphosphonate drugs are recommended as initial treatment [1,3,7,10]. Bisphosphonates appear to be beneficial in reducing the expansion of the bone lesion due to the antiosteoclastic activity and its anti-inflammatory effect, which can contribute to pain control [9].…”

“…Bisphosphonates appear to be beneficial in reducing the expansion of the bone lesion due to the antiosteoclastic activity and its anti-inflammatory effect, which can contribute to pain control [9]. Disease-modifying drugs, steroids and anti-TNFα have been used in severe and recurring cases [1,3,7,10,11,12]. Despite reports of a variable response to the use of anti-TNF [11,12], in this case the clinical and laboratory response had been sustained to date, with about 4 months of use of the biological medication, corroborating the reports of clinical and image improvement with the use of anti-TNF.…”

“…and other authors [4,6,7]. There are recent reports of IL-1 antagonists, with variable results [7]. The objective with this report is to present a case to the literature regarding the response to the use of anti-TNF (infliximab) after failure with the use of anti-inflammatory drugs, methotrexate and bisphosphonates.…”

“…The use of synthetic DMARDS such as methotrexate or sulfasalazine, use of anti-TNF or the use of bisphosphonates appear in reports as drugs with potential for disease control, as reported by Taddio et.al. and other authors [4,6,7]. There are recent reports of IL-1 antagonists, with variable results [7].…”

“…CNO remains a diagnosis of exclusion. The presence of bone pain associated with edema, local heat, fractures, cutaneous lesions (including palmoplantar pustulosis, psoriasis and acne), peripheral arthritis, and discrete elevations of evidence of inflammatory activity suggest the diagnosis [7].…”