European Journal of Pediatrics

, Volume 178, Issue 1, pp 89–95 | Cite as

The role of Cutibacterium acnes in auto-inflammatory bone disorders

  • Petra ZimmermannEmail author
  • Nigel CurtisEmail author
Original Article


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.


SAPHO Spondyloarthopathies Chronic recurrent multifocal osteomyelitis CRMO DSOM Osteitis Hyperostosis Synovitis Pustulosis Osteomyelitis 


C. acnes

Cutibacterium acnes


Chronic nonbacterial osteomyelitis


Chronic recurrent multifocal osteomyelitis


Diffuse sclerosing osteomyelitis of the mandible




Palmoplantar pustulosis


Synovitis, acne, pustulosis, hyperostosis and osteitis


Tumour necrosis factor


Authors’ contributions

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


Informed consent



  1. 1.
    Assmann G, Kueck O, Kirchhoff T, Rosenthal H, Voswinkel J, Pfreundschuh M, Zeidler H, Wagner AD (2009) Efficacy of antibiotic therapy for SAPHO syndrome is lost after its discontinuation: an interventional study. Arthritis Res Ther 11(5):R140CrossRefGoogle Scholar
  2. 2.
    Bae Y, Ito T, Iida T, Uchida K, Sekine M, Nakajima Y, Kumagai J, Yokoyama T, Kawachi H, Akashi T, Eishi Y (2014) Intracellular Propionibacterium acnes infection in glandular epithelium and stromal macrophages of the prostate with or without cancer. PLoS One 9(2):e90324CrossRefGoogle Scholar
  3. 3.
    Beretta-Piccoli BC, Sauvain MJ, Gal I, Schibler A, Saurenmann T, Kressebuch H, Bianchetti MG (2000) Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in childhood: a report of ten cases and review of the literature. Eur J Pediatr 159(8):594–601CrossRefGoogle Scholar
  4. 4.
    Berthelot JM, Corvec S, Hayem G (2018) SAPHO, autophagy, IL-1, FoxO1, and Propionibacterium (Cutibacterium) acnes. Joint Bone Spine 85(2):171–176CrossRefGoogle Scholar
  5. 5.
    Bossard DA, Ledergerber B, Zingg PO, Gerber C, Zinkernagel AS, Zbinden R, Achermann Y (2016) Optimal length of cultivation time for isolation of Propionibacterium acnes in suspected bone and joint infections is more than 7 days. J Clin Microbiol 54(12):3043–3049CrossRefGoogle Scholar
  6. 6.
    Burkhart CN, Burkhart CG (2006) Genome sequence of Propionibacterium acnes reveals immunogenic and surface-associated genes confirming existence of the acne biofilm. Int J Dermatol 45(7):872CrossRefGoogle Scholar
  7. 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. 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
  9. 9.
    Colina M, Govoni M, Orzincolo C, Trotta F (2009) Clinical and radiologic evolution of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: a single center study of a cohort of 71 subjects. Arthritis Rheum 61(6):813–821CrossRefGoogle Scholar
  10. 10.
    Collert S, Isacson J (1982) Chronic sclerosing osteomyelitis (Garre). Clin Orthop Relat Res 164:136–140Google Scholar
  11. 11.
    Crane JK, Hohman DW, Nodzo SR, Duquin TR (2013) Antimicrobial susceptibility of Propionibacterium acnes isolates from shoulder surgery. Antimicrob Agents Chemother 57(7):3424–3426CrossRefGoogle Scholar
  12. 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
  13. 13.
    Edlund E, Johnsson U, Lidgren L, Pettersson H, Sturfelt G, Svensson B, Theander J, Willen H (1988) Palmoplantar pustulosis and sternocostoclavicular arthro-osteitis. Ann Rheum Dis 47(10):809–815CrossRefGoogle Scholar
  14. 14.
    Frid P, Tornes K, Nielsen O, Skaug N (2009) Primary chronic osteomyelitis of the jaw--a microbial investigation using cultivation and DNA analysis: a pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107(5):641–647CrossRefGoogle Scholar
  15. 15.
    Furustrand Tafin U, Corvec S, Betrisey B, Zimmerli W, Trampuz A (2012) Role of rifampin against Propionibacterium acnes biofilm in vitro and in an experimental foreign-body infection model. Antimicrob Agents Chemother 56(4):1885–1891CrossRefGoogle Scholar
  16. 16.
    Gerster JC, Lagier R, Livio JJ (1990) Propionibacterium acnes in a spondylitis with palmoplantar pustulosis. Ann Rheum Dis 49(5):337–338CrossRefGoogle Scholar
  17. 17.
    Govoni M, Colina M, Massara A, Trotta F (2009) SAPHO syndrome and infections. Autoimmun Rev 8(3):256–259CrossRefGoogle Scholar
  18. 18.
    Hayem G, Bouchaud-Chabot A, Benali K, Roux S, Palazzo E, Silbermann-Hoffman O, Kahn MF, Meyer O (1999) SAPHO syndrome: a long-term follow-up study of 120 cases. Semin Arthritis Rheum 29(3):159–171CrossRefGoogle Scholar
  19. 19.
    Hurtado-Nedelec M, Chollet-Martin S, Nicaise-Roland P, Grootenboer-Mignot S, Ruimy R, Meyer O, Hayem G (2008) Characterization of the immune response in the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Rheumatology (Oxford, England) 47(8):1160–1167CrossRefGoogle Scholar
  20. 20.
    Jacobsson S, Dahlen G, Moller AJ (1982) Bacteriologic and serologic investigation in diffuse sclerosing osteomyelitis (DSO) of the mandible. Oral Surg Oral Med Oral Pathol 54(5):506–512CrossRefGoogle Scholar
  21. 21.
    Kaiser D, Bolt I, Hofer M, Relly C, Berthet G, Bolz D, Saurenmann T (2015) Chronic nonbacterial osteomyelitis in children: a retrospective multicenter study. Pediatr Rheumatol Online J 13:25CrossRefGoogle Scholar
  22. 22.
    Kalis C, Gumenscheimer M, Freudenberg N, Tchaptchet S, Fejer G, Heit A, Akira S, Galanos C, Freudenberg MA (2005) Requirement for TLR9 in the immunomodulatory activity of Propionibacterium acnes. J Immunol 174(7):4295–4300CrossRefGoogle Scholar
  23. 23.
    Khassebaf J, Hellmark B, Davidsson S, Unemo M, Nilsdotter-Augustinsson A, Soderquist B (2015) Antibiotic susceptibility of Propionibacterium acnes isolated from orthopaedic implant-associated infections. Anaerobe 32:57–62CrossRefGoogle Scholar
  24. 24.
    King SM, Laxer RM, Manson D, Gold R (1987) Chronic recurrent multifocal osteomyelitis: a noninfectious inflammatory process. Pediatr Infect Dis J 6(10):907–911CrossRefGoogle Scholar
  25. 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. 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. 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
  28. 28.
    Li ZJ, Choi DK, Sohn KC, Seo MS, Lee HE, Lee Y, Seo YJ, Lee YH, Shi G, Zouboulis CC, Kim CD, Lee JH, Im M (2014) Propionibacterium acnes activates the NLRP3 inflammasome in human sebocytes. J Invest Dermatol 134(11):2747–2756CrossRefGoogle Scholar
  29. 29.
    Nguyen MT, Borchers A, Selmi C, Naguwa SM, Cheema G, Gershwin ME (2012) The SAPHO syndrome. Semin Arthritis Rheum 42(3):254–265CrossRefGoogle Scholar
  30. 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
  31. 31.
    Perry A, Lambert P (2011) Propionibacterium acnes: infection beyond the skin. Expert Rev Anti-Infect Ther 9(12):1149–1156CrossRefGoogle Scholar
  32. 32.
    Piggott DA, Higgins YM, Melia MT, Ellis B, Carroll KC, McFarland EG et al (2016) Characteristics and treatment outcomes of Propionibacterium acnes prosthetic shoulder infections in adults. Open Forum Infect Dis 3(1):ofv191CrossRefGoogle Scholar
  33. 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
  34. 34.
    Qin M, Pirouz A, Kim MH, Krutzik SR, Garban HJ, Kim J (2014) Propionibacterium acnes induces IL-1beta secretion via the NLRP3 inflammasome in human monocytes. J Invest Dermatol 134(2):381–388CrossRefGoogle Scholar
  35. 35.
    Reith JD, Bauer TW, Schils JP (1996) Osseous manifestations of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. Am J Surg Pathol 20(11):1368–1377CrossRefGoogle Scholar
  36. 36.
    Sahdo B, Sarndahl E, Elgh F, Soderquist B (2013) Propionibacterium acnes activates caspase-1 in human neutrophils. APMIS 121(7):652–663CrossRefGoogle Scholar
  37. 37.
    Schaeverbeke T, Lequen L, de Barbeyrac B, Labbe L, Bebear CM, Morrier Y et al (1998) Propionibacterium acnes isolated from synovial tissue and fluid in a patient with oligoarthritis associated with acne and pustulosis. Arthritis Rheum 41(10):1889–1893CrossRefGoogle Scholar
  38. 38.
    Serushan M, Spencer DL, Yeh WL, Kaminski M, Skosey JL (1982) Osteomyelitis of cervical spine from Propionibacterium acnes. Arthritis Rheum 25(3):346–348CrossRefGoogle Scholar
  39. 39.
    Sharma M, Ferguson PJ (2013) Autoinflammatory bone disorders: update on immunologic abnormalities and clues about possible triggers. Curr Opin Rheumatol 25(5):658–664CrossRefGoogle Scholar
  40. 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
  41. 41.
    Trimble BS, Evers CJ, Ballaron SA, Young JM (1987) Intraarticular injection of Propionibacterium acnes causes an erosive arthritis in rats. Agents Actions 21(3–4):281–283CrossRefGoogle Scholar
  42. 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

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PaediatricsThe University of MelbourneParkvilleAustralia
  2. 2.Infectious Diseases UnitThe Royal Children’s Hospital MelbourneParkvilleAustralia
  3. 3.Infectious Diseases & Microbiology Research GroupMurdoch Children’s Research InstituteParkvilleAustralia
  4. 4.Infectious Diseases UnitUniversity of Basel Children’s HospitalBaselSwitzerland

Personalised recommendations