Department of Paediatrics, The University of Melbourne, Parkville, Australia.
Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Parkville, 3052, Australia.
Eur J Pediatr. 2019 Jan;178(1):89-95. doi: 10.1007/s00431-018-3263-2. Epub 2018 Oct 15.
Chronic nonbacterial osteomyelitis (CNO) and SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome are auto-inflammatory disorders manifesting as chronic inflammation of bones and joints, which in SAPHO is often accompanying by skin changes. The aetiology of these diseases is unknown, but includes genetic, infectious and immunological components. It has been proposed that Cutibacterium (formerly Propionibacterium) acnes plays a role in the pathogenesis. In this review, we summarise reported cases of CNO or SAPHO syndrome in which C. acnes has been isolated from bones. To identify cases, a search was done in May 2018 using the MEDLINE Ovid interface (1946 to present). We found 14 publications reporting 98 patients with auto-inflammatory bone disorders, of whom 48 (49%) had positive bone biopsies for C. acnes. This bacterium was more frequently isolated from open biopsies than percutaneous ones (43/69 (62%) vs 1/7 (14%); p = 0.04) and biopsies were more frequently positive in patients who presented with simultaneous skin manifestations (19/36 (53%) vs 4/12 (33%); p = 0.03).Conclusion: In patients with CNO or SAPHO, C. acnes can be isolated from open biopsies suggesting that in these patients, C. acnes might be a pathogen rather than a contaminant. The fact that biopsies are more frequently positive in patients who present with simultaneous skin manifestations suggests that these individuals might have a genetic predisposition for impaired clearance of C. acnes. What is known • Chronic nonbacterial osteomyelitis (CNO) and SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome are auto-inflammatory disorders manifesting as inflammation of bones. Both diseases are an important differential diagnosis in children who present with symptoms of (multifocal) osteomyelitis. • The pathogenesis of CNO and SAPHO is multifactorial emcompassing genetic, infectious and immunological components, including interleukin (IL)-1 dysregulation. There is a controversy as to whether Cutibacterium (formerly Propionibacterium) acnes plays a role in the aetiology of CNO and SAPHO. It has been postulated that the presence of C. acnes might trigger auto-inflammatory chronic inflammation in genetically predisposed individuals. What is new • In patients with CNO or SAPHO, C. acnes can be isolated more frequently from open biopsies, than from percutaneous ones, suggesting that C. acnes might be a pathogen rather than a contaminant. • Biopsies are more frequently positive in patients who present with simultaneous skin manifestations suggesting that these individuals might have a genetic predisposition for impaired clearance of C. acnes. Impaired C. acnes clearance likely leads to increased IL-1 beta (β) production by skin cells, bone cells and phagocytes, which is one of the main cytokines underlying chronic inflammatory bone disorders.
慢性非细菌性骨髓炎 (CNO) 和 SAPHO (滑膜炎、痤疮、脓疱病、骨肥厚和骨炎) 综合征是表现为骨骼和关节慢性炎症的自身炎症性疾病，SAPHO 常伴有皮肤改变。这些疾病的病因尚不清楚，但包括遗传、感染和免疫成分。有人提出，痤疮丙酸杆菌（以前称为丙酸杆菌）在发病机制中起作用。在这篇综述中，我们总结了报告的 CNO 或 SAPHO 综合征病例，其中从骨骼中分离出痤疮丙酸杆菌。为了确定病例，于 2018 年 5 月使用 MEDLINE Ovid 界面（1946 年至今）进行了搜索。我们发现了 14 篇报道自身炎症性骨病患者的文献，其中 48 例（49%）骨骼活检痤疮丙酸杆菌阳性。与经皮活检相比，该细菌从开放性活检中更常被分离出来（43/69（62%）与 1/7（14%）；p=0.04），并且在同时出现皮肤表现的患者中活检更常为阳性（19/36（53%）与 4/12（33%）；p=0.03）。结论：在 CNO 或 SAPHO 患者中，痤疮丙酸杆菌可从开放性活检中分离出来，这表明在这些患者中，痤疮丙酸杆菌可能是病原体而不是污染物。在同时出现皮肤表现的患者中，活检更常为阳性，这表明这些个体可能存在清除痤疮丙酸杆菌能力受损的遗传易感性。已知：慢性非细菌性骨髓炎 (CNO) 和 SAPHO（滑膜炎、痤疮、脓疱病、骨肥厚和骨炎）综合征是表现为骨骼炎症的自身炎症性疾病。这两种疾病都是儿童出现（多灶性）骨髓炎症状时的重要鉴别诊断。CNO 和 SAPHO 的发病机制是多因素的，包括白细胞介素 (IL)-1 失调，涉及遗传、感染和免疫成分。关于痤疮丙酸杆菌是否在 CNO 和 SAPHO 的发病机制中起作用存在争议。有人推测，痤疮丙酸杆菌的存在可能会引发遗传易感个体的慢性炎症。新发现：在 CNO 或 SAPHO 患者中，与经皮活检相比，开放性活检中更常从骨骼中分离出痤疮丙酸杆菌，这表明痤疮丙酸杆菌可能是病原体而不是污染物。在同时出现皮肤表现的患者中，活检更常为阳性，这表明这些个体可能存在清除痤疮丙酸杆菌能力受损的遗传易感性。痤疮丙酸杆菌清除能力受损可能导致皮肤细胞、骨细胞和吞噬细胞产生更多的白细胞介素 (IL)-1β（β），这是慢性炎症性骨病的主要细胞因子之一。
