Taddio Andrea, Ferrara Giovanna, Insalaco Antonella, Pardeo Manuela, Gregori Massimo, Finetti Martina, Pastore Serena, Tommasini Alberto, Ventura Alessandro, Gattorno Marco
Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.
University of Trieste, Via dell'Istria 65/1, 34100, Trieste, Italy.
Pediatr Rheumatol Online J. 2017 Dec 29;15(1):87. doi: 10.1186/s12969-017-0216-7.
Chronic 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.
CNO 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.
CNO 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.
慢性非细菌性骨髓炎(CNO)是一种主要影响儿童的炎症性疾病。尽管其发病率被低估,但仍然罕见。因此,目前尚无诊断和治疗指南。本文旨在就日常临床实践中如何处理这些患者提供一些建议。
CNO的特点是隐匿性骨痛伴局部肿胀。有时可能出现发热、皮肤受累及关节炎等全身症状。放射学表现提示骨髓炎,尤其是多个部位受累时。CNO主要累及长骨的干骺端,但锁骨和下颌骨,即使是该疾病的罕见发病部位,也与CNO诊断高度相符。CNO的发病机制尚不清楚,但最近的研究结果强调了细胞因子如IL-1β和IL-10在疾病发病机制中的关键作用。此外,自身炎症综合征中存在非细菌性骨髓炎表明CNO本身可被视为一种自身炎症性疾病。鉴别诊断包括感染、恶性肿瘤、良性骨肿瘤、代谢紊乱及其他自身炎症性疾病。磁共振成像或计算机断层扫描的放射学表现可能具有很强的提示性。因此,对于临床状况良好、多灶性病变且放射学表现高度相符的患者,可避免进行骨活检。非甾体类抗炎药是首选治疗药物。皮质类固醇、甲氨蝶呤、双膦酸盐、TNFα抑制剂和IL-1阻滞剂也有一定疗效;但二线治疗的选择取决于骨病变部位、全身症状的存在情况及患者的临床状况。
CNO可能难以识别,在诊断和治疗方面尚无共识。具有特征性放射学表现的多灶性骨病变强烈提示CNO。关于非甾体类抗炎药治疗失败后的最佳治疗方案尚无相关数据。