The role of Cutibacterium acnes in auto-inflammatory bone disorders
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).
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.
KeywordsSAPHO Spondyloarthopathies Chronic recurrent multifocal osteomyelitis CRMO DSOM Osteitis Hyperostosis Synovitis Pustulosis Osteomyelitis
- C. acnes
Chronic nonbacterial osteomyelitis
Chronic recurrent multifocal osteomyelitis
Diffuse sclerosing osteomyelitis of the mandible
Synovitis, acne, pustulosis, hyperostosis and osteitis
Tumour necrosis factor
PZ drafted the initial manuscript and approved the final manuscript as submitted. NC critically reviewed and revised the manuscript and approved the final manuscript as submitted.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest.
Research involving human participants and/or animals
- 7.Chamot AM, Benhamou CL, Kahn MF, Beraneck L, Kaplan G, Prost A (1987) Acne-pustulosis-hyperostosis-osteitis syndrome. Results of a national survey. 85 cases. Rev Rhum Mal Osteoartic 54(3):187–196Google Scholar
- 8.Colina M, Lo Monaco A, Khodeir M, Trotta F (2007) Propionibacterium acnes and SAPHO syndrome: a case report and literature review. Clin Exp Rheumatol 25(3):457–460Google Scholar
- 10.Collert S, Isacson J (1982) Chronic sclerosing osteomyelitis (Garre). Clin Orthop Relat Res 164:136–140Google Scholar
- 12.Do TT, Strub WM, Witte D (2003) Subacute Propionibacterium acnes osteomyelitis of the spine in an adolescent. J Pediatr Orthop B 12(4):284–287Google Scholar
- 25.Kirchhoff T, Merkesdal S, Rosenthal H, Prokop M, Chavan A, Wagner A, Mai U, Hammer M, Zeidler H, Galanski M (2003) Diagnostic management of patients with SAPHO syndrome: use of MR imaging to guide bone biopsy at CT for microbiological and histological work-up. Eur Radiol 13(10):2304–2308CrossRefGoogle Scholar
- 26.Kistowska M, Gehrke S, Jankovic D, Kerl K, Fettelschoss A, Feldmeyer L, Fenini G, Kolios A, Navarini A, Ganceviciene R, Schauber J, Contassot E, French LE (2014) IL-1beta drives inflammatory responses to propionibacterium acnes in vitro and in vivo. J Invest Dermatol 134(3):677–685CrossRefGoogle Scholar
- 27.Kotilainen P, Merilahti-Palo R, Lehtonen OP, Manner I, Helander I, Mottonen T et al (1996) Propionibacterium acnes isolated from sternal osteitis in a patient with SAPHO syndrome. J Rheumatol 23(7):1302–1304Google Scholar
- 30.Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, Rao N, Hanssen A, Wilson WR, Infectious Diseases Society of America (2013) Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 56(1):e1–e25CrossRefGoogle Scholar
- 33.Pillon P, Pajon A, Juvin R, Gaudin P, Tourne Y, Pasquier B, Phelip X (1992) Tibial hyperostosis and Propionibacterium acnes. Rev Rhum Mal Osteoartic 59(5):349–351Google Scholar
- 40.Tebruegge M, Jones C, de Graaf H, Sukhtankar P, Allan RN, Howlin RP, Browning D, Schuster H, Pallett A, Patel S, Faust SN (2015) Invasive Propionibacterium acnes infections in a non-selective patient cohort: clinical manifestations, management and outcome. Eur J Clin Microbiol Infect Dis 34(3):527–534CrossRefGoogle Scholar
- 42.Zimmermann P, Curtis N (2016) Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome - a challenging diagnosis not to be missed. J Inf Secur 72(Suppl):S106–S114Google Scholar