Dealing with Chronic Non-Bacterial Osteomyelitis: a practical approach

Abstract

BackgroundChronic Non-Bacterial Osteomyelitis (CNO) is an inflammatory disorder that primarily affects children. Although underestimated, its incidence is rare. For these reasons, no diagnostic and no therapeutic guidelines exist. The manuscript wants to give some suggestions on how to deal with these patients in the every-day clinical practice.Main bodyCNO is characterized by insidious onset of bone pain with local swelling. Systemic symptoms such as fever, skin involvement and arthritis may be sometimes present. Radiological findings are suggestive for osteomyelitis, in particular if multiple sites are involved. CNO predominantly affects metaphyses of long bones, but clavicle and mandible, even if rare localizations of the disease, are very consistent with CNO diagnosis. CNO pathogenesis is still unknown, but recent findings highlighted the crucial role of cytokines such as IL-1β and IL-10 in disease pathogenesis. Moreover, the presence of non-bacterial osteomyelitis among autoinflammatory syndromes suggests that CNO could be considered an autoinflammatory disease itself. Differential diagnosis includes infections, malignancies, benign bone tumors, metabolic disorders and other autoinflammatory disorders. Radiologic findings, either with Magnetic Resonance or with Computer Scan, may be very suggestive. For this reason in patients in good clinical conditions, with multifocal localization and very consistent radiological findings bone biopsy could be avoided. Non-Steroidal Anti-Inflammatory Drugs are the first-choice treatment. Corticosteroids, methotrexate, bisphosphonates, TNFα-inhibitors and IL-1 blockers have also been used with some benefit; but the choice of the second line treatment depends on bone lesions localizations, presence of systemic features and patients’ clinical conditions.ConclusionCNO may be difficult to identify and no consensus exist on diagnosis and treatment. Multifocal bone lesions with characteristic radiological findings are very suggestive of CNO. No data exist on best treatment option after Non-Steroidal Anti-Inflammatory Drugs failure.

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

“…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].…”

“…Its bone lesions can be unifocal of multifocal, initially osteolytic, and posteriorly sclerotic or hyperostotic [2]. The primary targets of the primary disease are children, in which it mainly attacks metaphyses of long bones, but may occur anywhere in the skeleton [1,3,4]. Skin, eyes and lungs may also be affected by inflammation [1,3].…”

“…In the pathophysiology of the disease there are data demonstrating an imbalance of pro-inflammatory and anti-inflammatory interleukins, represented by IL-1β, IL-6, Anti-TNF and IL-10, respectively [5]. The discovery of the pathophysiology of the disease reinforces a hypothesis of possible autoinflammatory disease [4]. Current evidence shows that chronic aseptic osteomyelitis has a relevant genetic component.…”

Response of Different Treatment Protocols to Treat Chronic Non-Bacterial Osteomyelitis (CNO) of the Mandible in Adult Patients: A Systematic Review

“…Patients with CNO show an underproduction of anti-inflammatory cytokines (interleukin-10) and overproduction of proinflammatory cytokines (tumor necrosis factor-α (TNFα) and interleukin-1). Due to the spontaneous hyperproduction of proinflammatory cytokines without autoimmunity features, CNO is classified as an autoinflammatory disease, thus falling into the rheumatic group of diseases [7][8][9][10][11][12][13][14]. The oral and maxillofacial surgery literature also discusses further factors as etiology of CNO.…”

“…The initial patient consultation with regard to the CNO of the mandible often takes place at the dentist since the pain is misinterpreted as toothache or, in combination with swelling, as an abscessing process. A possible moderate increase in CRP (C-reactive protein) in the serum within the scope of CNO may also lead to misinterpretation [14].…”