http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2014; 24(4): 697–698 © 2014 Japan College of Rheumatology DOI: 10.3109/14397595.2013.874760
LETTER
Antibiotics may be useful in the treatment of SAPHO syndrome Matteo Colina1 and Francesco Trotta2 1Rheumatology Service, Section of Internal Medicine, Department of Medicine, Ospedale “Santa Maria della Scaletta”,
Bologna, Italy
and 2Rheumatology Department, University of Ferrara, Ferrara, Italy
Mod Rheumatol Downloaded from informahealthcare.com by Nyu Medical Center on 05/22/15 For personal use only.
Keywords SAPHO syndrome, Antibiotics, Propionibacterium acnes, Autoimmunity History Received 25 March 2013 Accepted 8 April 2013 Published online 20 April 2013
Dear Editor, We have read with great interest the article by Takizawa et al. [1] recently published in Modern Rheumatology, on the efficacy of minocycline in a patient with SAPHO syndrome. We fully agree with Takizawa et al., both on the possibility that SAPHO syndrome presents with marked inflammation and on the serious differential diagnosis that a severe inflammation localised at the spine with a positive scintiscan may result. In the described case report, the authors had initially chosen for antibiotic therapy on the suspicion of septic discitis, but X-ray and computed tomography scan revealed hyperostotic changes and erosions in the right sternoclavicular joints, with inflammation in the adjacent soft tissues. In fact, these abnormalities on radiography are the hallmark of SAPHO syndrome [2]. We also agree with the authors that when inflammation of the surrounding soft tissue is detected, a biopsy should be mandatory in order to exclude malignancy. With regards to the use of tetracyclines—and antibiotics in general—in patients suffering from SAPHO syndrome, it is worth recalling that SAPHO syndrome is probably a primitive reactive osteitis in genetically predisposed subjects and that not only Propionibacterium acnes but also Staphylococcus aureus have been isolated from osteoarticular lesions in the anterior chest wall (ACW), spine, pustules and synovial fluid and tissue [2–7]. A wide range of other pathogens has been found, including Hemophilus parainfluenzae, Actinomycetes and Treponema pallidum [8]. However, at the present time, data from the literature favours Propionibacterium acnes, although this microorganisms has only been found occasionally in bacterial cultures. It is possible that the use of other procedures, such as PCR, would provide reliable data on the real frequency of P. acnes in osteitic bone lesions of SAPHO syndrome, leading to a better understanding of the aetio-pathogenesis of this disease. A low-virulence infection by P. acnes is probably an important trigger in the aetio-pathogenesis of SAPHO syndrome, especially when the microorganisms have Correspondence to: Matteo Colina, Dipartimento Medico, Unità Operativa Complessa di Medina Uno, Ospedale “Santa Maria della Scaletta”, Via Montericco, 4, Imola, 40026, Imola, Bologna, Italy. E-mail: [email protected]
access to the bone, thereby initiating or stimulating a chronic inflammatory response concomitant with systemic symptoms. Moreover, P. acnes can activate the complement and induces production and secretion of interleukin (IL)-1, IL-8 and tumour necrosis factor-alpha (TNF-α) [9]. In 2007 we described a case of SAPHO patient in which we were able to isolate P. acnes from a bone biopsy. In that case we treated the osteo-articular complaints of the patients with doxycycline because the antibiogram revealed that this tetracycline would be efficient. Noteworthy is that skin lesions have continued to recur regardless of this therapy [10]. Conversely, there has been evidence that TNF-α blocking agents and that IL-1 receptor antagonist anakinra is effective in SAPHO syndrome [2, 11, 12], suggesting that etiopathogenesis mechanisms are still elusive in this disease. In conclusion, we argue that antibiotics could be very useful in the treatment of SAPHO syndrome, especially in those cases characterised by a marked inflammatory response and in which the scintiscan reveals a focal “hot spot”, usually localised at the ACW. Nevertheless, it has recently been demonstrated that the efficacy of antibiotic therapy for SAPHO syndrome is lost after its discontinuation [13].
Conflict of interest None.
References 1. Takizawa Y, Murota A, Setoguchi K, Suzuki Y. Severe inflammation associated with synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome was markedly ameliorated by single use of minocycline. Mod Rheum. 2013. doi:10.1007/s10165-013-0843-x. 2. Colina M, Govoni M, Orzincolo C, Trotta F. Clinical and radiological evolution of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome: a single center study of a cohort of 71 subjects. Arthritis Rheum. 2009;61:813–21. 3. Rozin AP. SAPHO syndrome: is a range of pathogen-associated rheumatic disease extended?. Arthritis Res Ther. 2009;11:131. 4. Assmann G, Simon P. The SAPHO syndrome. Are microbes involved? Best Pract Res Clin Rheumatol. 2011;25:423–34.
698
M. Colina & F. Trotta
Mod Rheumatol Downloaded from informahealthcare.com by Nyu Medical Center on 05/22/15 For personal use only.
5. Schaeverbeke T, Lequen L, de Barbeyrac B, Labbé L, Bébéar CM, Morrier YM, et al. Propionibacterium acnes isolated from synovial tissue and fluid in a patient with oligoarthritis associated with acne and pustulosis. Arthritis Rheum. 1998;41:1889–93. 6. Edlund E, Johnsson U, Lidgren L, Pettersson H, Sturfelt G, Svensson B, et al. Palmo-plantar pustulosis and sternocosto-clavicular arthrtoosteitis. Ann Rheum Dis. 1988;47:809–15. 7. Kirchhoff T, Merkesdal S, Rosenthal H, Prokop M, Chavan A, Wagner A, et al. Diagnostic management of patient with SAPHO syndrome: use of MR imaging to guide bone biopsy at CT for microbiological and histological work-up. Eur Radiol. 2003;13:2304–8. 8. Amison Y, Rubibow A, Amital H. Secondary syphilis presenting as SAPHO syndrome features. Clin Exp Rheumatol. 2008;26:1119–21. 9. Govoni M, Colina M, Massara A, Trotta F. SAPHO syndrome and infections. Autoimmun Rev. 2009;8:256–9.
Mod Rheumatol, 2014; 24(4): 697–698
10. Colina M, Lo Monaco A, Khodeir M, Trotta F. Propionibacterium acnes and SAPHO syndrome: a case rport and literature review. Clin Exp Rheumatol. 2007;25:457–60. 11. Wagner AD, Andresen J, Jendro MC, Huselman JL, Zeidler H. Sustained response to tumour necrosis factor alpha-blocking agents in two patients with SAPHO syndrome. Arthritis Rheum. 2002;46:1965–8. 12. Colina M, Pizzirani C, Khodeir M, Falzoni S, Bruschi M, Trotta F, et al. Disregulation of P2X7 receptor-inflammasome axis in SAPHO syndrome: successful treatment with anakinra. Rheumatology. 2009;49: 1416–8. 13. Assmann G, Kueck O, Kirchhoff T, Rosenthal H, Voswinkel J, Pfreundschuh M, et al. Efficacy of antibiotic therapy for SAPHO syndrome is lost after its discontinuation: an interventional study. Arthritis Res Ther. 2009;11:R140.
LETTER
Antibiotics may be useful in the treatment of SAPHO syndrome Matteo Colina1 and Francesco Trotta2 1Rheumatology Service, Section of Internal Medicine, Department of Medicine, Ospedale “Santa Maria della Scaletta”,
Bologna, Italy
and 2Rheumatology Department, University of Ferrara, Ferrara, Italy
Mod Rheumatol Downloaded from informahealthcare.com by Nyu Medical Center on 05/22/15 For personal use only.
Keywords SAPHO syndrome, Antibiotics, Propionibacterium acnes, Autoimmunity History Received 25 March 2013 Accepted 8 April 2013 Published online 20 April 2013
Dear Editor, We have read with great interest the article by Takizawa et al. [1] recently published in Modern Rheumatology, on the efficacy of minocycline in a patient with SAPHO syndrome. We fully agree with Takizawa et al., both on the possibility that SAPHO syndrome presents with marked inflammation and on the serious differential diagnosis that a severe inflammation localised at the spine with a positive scintiscan may result. In the described case report, the authors had initially chosen for antibiotic therapy on the suspicion of septic discitis, but X-ray and computed tomography scan revealed hyperostotic changes and erosions in the right sternoclavicular joints, with inflammation in the adjacent soft tissues. In fact, these abnormalities on radiography are the hallmark of SAPHO syndrome [2]. We also agree with the authors that when inflammation of the surrounding soft tissue is detected, a biopsy should be mandatory in order to exclude malignancy. With regards to the use of tetracyclines—and antibiotics in general—in patients suffering from SAPHO syndrome, it is worth recalling that SAPHO syndrome is probably a primitive reactive osteitis in genetically predisposed subjects and that not only Propionibacterium acnes but also Staphylococcus aureus have been isolated from osteoarticular lesions in the anterior chest wall (ACW), spine, pustules and synovial fluid and tissue [2–7]. A wide range of other pathogens has been found, including Hemophilus parainfluenzae, Actinomycetes and Treponema pallidum [8]. However, at the present time, data from the literature favours Propionibacterium acnes, although this microorganisms has only been found occasionally in bacterial cultures. It is possible that the use of other procedures, such as PCR, would provide reliable data on the real frequency of P. acnes in osteitic bone lesions of SAPHO syndrome, leading to a better understanding of the aetio-pathogenesis of this disease. A low-virulence infection by P. acnes is probably an important trigger in the aetio-pathogenesis of SAPHO syndrome, especially when the microorganisms have Correspondence to: Matteo Colina, Dipartimento Medico, Unità Operativa Complessa di Medina Uno, Ospedale “Santa Maria della Scaletta”, Via Montericco, 4, Imola, 40026, Imola, Bologna, Italy. E-mail: [email protected]
access to the bone, thereby initiating or stimulating a chronic inflammatory response concomitant with systemic symptoms. Moreover, P. acnes can activate the complement and induces production and secretion of interleukin (IL)-1, IL-8 and tumour necrosis factor-alpha (TNF-α) [9]. In 2007 we described a case of SAPHO patient in which we were able to isolate P. acnes from a bone biopsy. In that case we treated the osteo-articular complaints of the patients with doxycycline because the antibiogram revealed that this tetracycline would be efficient. Noteworthy is that skin lesions have continued to recur regardless of this therapy [10]. Conversely, there has been evidence that TNF-α blocking agents and that IL-1 receptor antagonist anakinra is effective in SAPHO syndrome [2, 11, 12], suggesting that etiopathogenesis mechanisms are still elusive in this disease. In conclusion, we argue that antibiotics could be very useful in the treatment of SAPHO syndrome, especially in those cases characterised by a marked inflammatory response and in which the scintiscan reveals a focal “hot spot”, usually localised at the ACW. Nevertheless, it has recently been demonstrated that the efficacy of antibiotic therapy for SAPHO syndrome is lost after its discontinuation [13].
Conflict of interest None.
References 1. Takizawa Y, Murota A, Setoguchi K, Suzuki Y. Severe inflammation associated with synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome was markedly ameliorated by single use of minocycline. Mod Rheum. 2013. doi:10.1007/s10165-013-0843-x. 2. Colina M, Govoni M, Orzincolo C, Trotta F. Clinical and radiological evolution of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome: a single center study of a cohort of 71 subjects. Arthritis Rheum. 2009;61:813–21. 3. Rozin AP. SAPHO syndrome: is a range of pathogen-associated rheumatic disease extended?. Arthritis Res Ther. 2009;11:131. 4. Assmann G, Simon P. The SAPHO syndrome. Are microbes involved? Best Pract Res Clin Rheumatol. 2011;25:423–34.
698
M. Colina & F. Trotta
Mod Rheumatol Downloaded from informahealthcare.com by Nyu Medical Center on 05/22/15 For personal use only.
5. Schaeverbeke T, Lequen L, de Barbeyrac B, Labbé L, Bébéar CM, Morrier YM, et al. Propionibacterium acnes isolated from synovial tissue and fluid in a patient with oligoarthritis associated with acne and pustulosis. Arthritis Rheum. 1998;41:1889–93. 6. Edlund E, Johnsson U, Lidgren L, Pettersson H, Sturfelt G, Svensson B, et al. Palmo-plantar pustulosis and sternocosto-clavicular arthrtoosteitis. Ann Rheum Dis. 1988;47:809–15. 7. Kirchhoff T, Merkesdal S, Rosenthal H, Prokop M, Chavan A, Wagner A, et al. Diagnostic management of patient with SAPHO syndrome: use of MR imaging to guide bone biopsy at CT for microbiological and histological work-up. Eur Radiol. 2003;13:2304–8. 8. Amison Y, Rubibow A, Amital H. Secondary syphilis presenting as SAPHO syndrome features. Clin Exp Rheumatol. 2008;26:1119–21. 9. Govoni M, Colina M, Massara A, Trotta F. SAPHO syndrome and infections. Autoimmun Rev. 2009;8:256–9.
Mod Rheumatol, 2014; 24(4): 697–698
10. Colina M, Lo Monaco A, Khodeir M, Trotta F. Propionibacterium acnes and SAPHO syndrome: a case rport and literature review. Clin Exp Rheumatol. 2007;25:457–60. 11. Wagner AD, Andresen J, Jendro MC, Huselman JL, Zeidler H. Sustained response to tumour necrosis factor alpha-blocking agents in two patients with SAPHO syndrome. Arthritis Rheum. 2002;46:1965–8. 12. Colina M, Pizzirani C, Khodeir M, Falzoni S, Bruschi M, Trotta F, et al. Disregulation of P2X7 receptor-inflammasome axis in SAPHO syndrome: successful treatment with anakinra. Rheumatology. 2009;49: 1416–8. 13. Assmann G, Kueck O, Kirchhoff T, Rosenthal H, Voswinkel J, Pfreundschuh M, et al. Efficacy of antibiotic therapy for SAPHO syndrome is lost after its discontinuation: an interventional study. Arthritis Res Ther. 2009;11:R140.
