Skip to main content

Advertisement

SpringerLink
Log in

The role of Cutibacterium acnes in auto-inflammatory bone disorders

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

C. acnes :

Cutibacterium acnes

CNO:

Chronic nonbacterial osteomyelitis

CRMO:

Chronic recurrent multifocal osteomyelitis

DSOM:

Diffuse sclerosing osteomyelitis of the mandible

IL:

Interleukin

PPP:

Palmoplantar pustulosis

SAPHO:

Synovitis, acne, pustulosis, hyperostosis and osteitis

TNF:

Tumour necrosis factor

References

  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):R140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):e90324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):594–601

    Article  CAS  PubMed  Google Scholar 

  4. Berthelot JM, Corvec S, Hayem G (2018) SAPHO, autophagy, IL-1, FoxO1, and Propionibacterium (Cutibacterium) acnes. Joint Bone Spine 85(2):171–176

    Article  CAS  PubMed  Google Scholar 

  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):3043–3049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):872

    Article  PubMed  Google Scholar 

  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):187–196

    CAS  PubMed  Google 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):457–460

    CAS  PubMed  Google Scholar 

  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):813–821

    Article  PubMed  Google Scholar 

  10. Collert S, Isacson J (1982) Chronic sclerosing osteomyelitis (Garre). Clin Orthop Relat Res 164:136–140

    Google Scholar 

  11. Crane JK, Hohman DW, Nodzo SR, Duquin TR (2013) Antimicrobial susceptibility of Propionibacterium acnes isolates from shoulder surgery. Antimicrob Agents Chemother 57(7):3424–3426

    Article  CAS  PubMed  PubMed Central  Google 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):284–287

    PubMed  Google Scholar 

  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):809–815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):641–647

    Article  PubMed  Google Scholar 

  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):1885–1891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gerster JC, Lagier R, Livio JJ (1990) Propionibacterium acnes in a spondylitis with palmoplantar pustulosis. Ann Rheum Dis 49(5):337–338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Govoni M, Colina M, Massara A, Trotta F (2009) SAPHO syndrome and infections. Autoimmun Rev 8(3):256–259

    Article  CAS  PubMed  Google Scholar 

  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):159–171

    Article  CAS  PubMed  Google Scholar 

  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):1160–1167

    Article  CAS  Google Scholar 

  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):506–512

    Article  CAS  PubMed  Google Scholar 

  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 13:25

    Article  PubMed  PubMed Central  Google Scholar 

  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):4295–4300

    Article  CAS  PubMed  Google Scholar 

  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 32:57–62

    Article  CAS  PubMed  Google Scholar 

  24. King SM, Laxer RM, Manson D, Gold R (1987) Chronic recurrent multifocal osteomyelitis: a noninfectious inflammatory process. Pediatr Infect Dis J 6(10):907–911

    Article  CAS  PubMed  Google 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):2304–2308

    Article  PubMed  Google 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):677–685

    Article  CAS  PubMed  Google 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):1302–1304

    CAS  PubMed  Google Scholar 

  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):2747–2756

    Article  CAS  PubMed  Google Scholar 

  29. Nguyen MT, Borchers A, Selmi C, Naguwa SM, Cheema G, Gershwin ME (2012) The SAPHO syndrome. Semin Arthritis Rheum 42(3):254–265

    Article  PubMed  Google 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–e25

    Article  PubMed  Google Scholar 

  31. Perry A, Lambert P (2011) Propionibacterium acnes: infection beyond the skin. Expert Rev Anti-Infect Ther 9(12):1149–1156

    Article  CAS  PubMed  Google Scholar 

  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):ofv191

    Article  PubMed  Google 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):349–351

    CAS  PubMed  Google Scholar 

  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):381–388

    Article  CAS  PubMed  Google Scholar 

  35. Reith JD, Bauer TW, Schils JP (1996) Osseous manifestations of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. Am J Surg Pathol 20(11):1368–1377

    Article  CAS  PubMed  Google Scholar 

  36. Sahdo B, Sarndahl E, Elgh F, Soderquist B (2013) Propionibacterium acnes activates caspase-1 in human neutrophils. APMIS 121(7):652–663

    Article  CAS  PubMed  Google Scholar 

  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):1889–1893

    Article  CAS  PubMed  Google Scholar 

  38. Serushan M, Spencer DL, Yeh WL, Kaminski M, Skosey JL (1982) Osteomyelitis of cervical spine from Propionibacterium acnes. Arthritis Rheum 25(3):346–348

    Article  CAS  PubMed  Google Scholar 

  39. Sharma M, Ferguson PJ (2013) Autoinflammatory bone disorders: update on immunologic abnormalities and clues about possible triggers. Curr Opin Rheumatol 25(5):658–664

    Article  CAS  PubMed  PubMed Central  Google 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):527–534

    Article  CAS  PubMed  Google Scholar 

  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):281–283

    Article  CAS  PubMed  Google 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–S114

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Paediatrics, The University of Melbourne, Parkville, Australia

    Petra Zimmermann & Nigel Curtis

  2. Infectious Diseases Unit, The Royal Children’s Hospital Melbourne, Parkville, 3052, Australia

    Petra Zimmermann & Nigel Curtis

  3. Infectious Diseases & Microbiology Research Group, Murdoch Children’s Research Institute, Parkville, Australia

    Petra Zimmermann & Nigel Curtis

  4. Infectious Diseases Unit, University of Basel Children’s Hospital, Basel, Switzerland

    Petra Zimmermann

Authors
  1. Petra Zimmermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nigel Curtis
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Corresponding authors

Correspondence to Petra Zimmermann or Nigel Curtis.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Research involving human participants and/or animals

N/A

Informed consent

N/A

Additional information

Communicated by Nicole Ritz

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zimmermann, P., Curtis, N. The role of Cutibacterium acnes in auto-inflammatory bone disorders. Eur J Pediatr 178, 89–95 (2019). https://doi.org/10.1007/s00431-018-3263-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-018-3263-2

Keywords

Search

Navigation