Clinical Rheumatology

, Volume 39, Issue 1, pp 177–187 | Cite as

SAPHO: has the time come for tailored therapy?

  • Adelaide Sofia Batalha FigueiredoEmail author
  • Ana Luísa Oliveira
  • António Caetano
  • Maria Francisca Moraes-Fontes
Case Based Review


SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a heterogeneous condition combining osteoarticular and cutaneous manifestations. Conventional treatments are mostly ineffective. We hereby report two patients, the first with an aggressive form of disease and the second with an incomplete response to two different anti-TNF-α agents. Both were successfully treated with tocilizumab and ustekinumab, respectively, over a long period of time. A narrative review of a biological therapy in SAPHO syndrome yielded very little information on the specific use of these agents. We highlight the advantages of personalising therapy and describe emerging promising treatments for this disease.


Anti-IL-1 agents Anti-IL-12/IL-23 agents Anti-IL-6 agents Anti-TNF-α agents SAPHO syndrome Treatment 


Compliance with ethical standards




Both patients gave informed consent for the publication of their case report and related images.


  1. 1.
    Kahn M-F, Khan MA (1994) The SAPHO syndrome. Baillieres Clin Rheumatol 8:333–362. CrossRefPubMedGoogle Scholar
  2. 2.
    Li C, Cao Y, Zhang W (2018) Clinical heterogeneity of SAPHO syndrome: challenge of diagnosis. Mod Rheumatol 28:432–434. CrossRefPubMedGoogle Scholar
  3. 3.
    Li C, Zuo Y, Wu N, Li L, Li F, Zhang W, Xu W, Zhao X, Jing H, Pan Q, Zhou W, Shi X, Fan Y, Wang J, Liu S, Liu Z, Zhang F, Zeng X, Chen H, Zhang S, Liu J, Qiu G, Wu Z, Dong Z, Zhang W (2016) Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome: a single centre study of a cohort of 164 patients. Rheumatology (Oxford) 55:1023–1030. CrossRefGoogle Scholar
  4. 4.
    Firinu D, Garcia-Larsen V, Manconi PE, Del Giacco SR (2016) SAPHO syndrome: current developments and approaches to clinical treatment. Curr Rheumatol Rep 18.
  5. 5.
    Firinu D, Murgia G, Lorrai M, Barca M, Peralta M, Manconi P, Giacco S (2014) Biological treatments for SAPHO syndrome: an update. Inflamm Allergy Drug Targets 13:199–205. CrossRefPubMedGoogle Scholar
  6. 6.
    Daoussis D, Konstantopoulou G, Kraniotis P, Sakkas L, Liossis SN (2018) Biologics in SAPHO syndrome: a systematic review. Semin Arthritis Rheum 48:618–625. CrossRefPubMedGoogle Scholar
  7. 7.
    Colina M, Pizzirani C, Khodeir M, Falzoni S, Bruschi M, Trotta F, di Virgilio F (2010) Dysregulation of P2X7receptor-inflammasome axis in SAPHO syndrome: successful treatment with anakinra. Rheumatology 49:1416–1418. CrossRefPubMedGoogle Scholar
  8. 8.
    Wendling D, Prati C, Aubin F (2012) Anakinra treatment of SAPHO syndrome: short-term results of an open study. Ann Rheum Dis 71:1098–1100. CrossRefPubMedGoogle Scholar
  9. 9.
    Cornillier H, Kervarrec T, Tabareau-Delalande F, Mammou S, Jonville Bera AP, Machet L (2016) Interstitial granulomatous dermatitis occurring in a patient with SAPHO syndrome one month after starting leflunomide, and subsequently disappearing with ustekinumab. Eur J Dermatol 26:614–615. CrossRefPubMedGoogle Scholar
  10. 10.
    Wendling D, Aubin F, Verhoeven F, Prati C (2017) IL-23/Th17 targeted therapies in SAPHO syndrome. A case series. Jt Bone Spine 84:733–735. CrossRefGoogle Scholar
  11. 11.
    Sato H, Wada Y, Hasegawa E, Nozawa Y, Nakatsue T, Ito T, Kuroda T, Saeki T, Umezu H, Suzuki Y, Nakano M, Narita I (2017) Adult-onset chronic recurrent multifocal osteomyelitis with high intensity of muscles detected by magnetic resonance imaging, successfully controlled with tocilizumab. Intern Med 56:2353–2360. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Adamo S, Nilsson J, Krebs A, Steiner U, Cozzio A, French LE, Kolios AGA (2018) Successful treatment of SAPHO syndrome with apremilast. Br J Dermatol 179:959–962. CrossRefPubMedGoogle Scholar
  13. 13.
    Yang Q, Zhao Y, Li C, Luo Y, Hao W, Zhang W (2018) Case report: successful treatment of refractory SAPHO syndrome with the JAK inhibitor tofacitinib. Medicine (Baltimore) 97:23–26. CrossRefGoogle Scholar
  14. 14.
    Wagner AD, Andresen J, Jendro MC, Hülsemann JL, Zeidler H (2002) Sustained response to tumor necrosis factor α-blocking agents in two patients with SAPHO syndrome. Arthritis Rheum 46:1965–1968. CrossRefPubMedGoogle Scholar
  15. 15.
    Ben Abdelghani K, Dran DG, Gottenberg JE et al (2010) Tumor necrosis factor-α blockers in SAPHO syndrome. J Rheumatol 37:1699–1704. CrossRefPubMedGoogle Scholar
  16. 16.
    Arias-Santiago S, Sanchez-Cano D, Callejas-Rubio JL, Fernández-Pugnaire MA, Ortego-Centeno N (2010) Adalimumab treatment for SAPHO syndrome. Acta Derm Venereol 90:301–302CrossRefGoogle Scholar
  17. 17.
    Fujita S, Kosaka N, Mito T, Hayashi H, Morita Y (2015) Development of aseptic subcutaneous abscess after tocilizumab therapy in a patient with SAPHO syndrome complicated by amyloid A amyloidosis. Int J Rheum Dis 18:476–479. CrossRefPubMedGoogle Scholar
  18. 18.
    Olivieri I, Padula A, Ciancio G, Salvarani C, Niccoli L, Cantini F (2002) Successful treatment of SAPHO syndrome with infliximab: report of two cases. Ann Rheum Dis 61:375–376CrossRefGoogle Scholar
  19. 19.
    Iqbal M, Kolodney MS (2005) Acne fulminans with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome treated with infliximab. J Am Acad Dermatol 52:S118–S120. CrossRefPubMedGoogle Scholar
  20. 20.
    Massara A, Cavazzini PL, Trotta F (2006) In SAPHO syndrome anti-TNF-α therapy may induce persistent amelioration of osteoarticular complaints, but may exacerbate cutaneous manifestations. Rheumatology 45:730–733. CrossRefPubMedGoogle Scholar
  21. 21.
    Sabugo F, Liberman C, Niedmann JP, Soto L, Cuchacovich M (2008) Infliximab can induce a prolonged clinical remission and a decrease in thyroid hormonal requirements in a patient with SAPHO syndrome and hypothyroidism. Clin Rheumatol 27:533–535. CrossRefPubMedGoogle Scholar
  22. 22.
    Moll C, Hernández MV, Cañete JD, Gómez-Puerta JA, Soriano A, Collado A, Sanmartí R (2008) Ilium osteitis as the main manifestation of the SAPHO syndrome: response to infliximab therapy and review of the literature. Semin Arthritis Rheum 37:299–306. CrossRefPubMedGoogle Scholar
  23. 23.
    Fruehauf J, Cierny-Modrè B, El-Shabrawi Caelen L et al (2009) Response to infliximab in SAPHO syndrome. BMJ Case Rep 2009:1–9. CrossRefGoogle Scholar
  24. 24.
    Castellví I, Bonet M, Narváez JA, Molina-Hinojosa JC (2010) Successful treatment of SAPHO syndrome with adalimumab: a case report. Clin Rheumatol 29:1205–1207. CrossRefPubMedGoogle Scholar
  25. 25.
    Vilar-Alejo J, Dehesa L, De La Rosa-del Rey P et al (2010) SAPHO syndrome with unusual cutaneous manifestations treated successfully with etanercept. Acta Derm Venereol 90:531–532. CrossRefPubMedGoogle Scholar
  26. 26.
    de Souza A, Solomon GE, Strober BE (2011) SAPHO syndrome associated with hidradenitis suppurativa successfully treated with infliximab and methotrexate. Bull NYU Hosp Jt Dis 69:185–187PubMedGoogle Scholar
  27. 27.
    Zhang LL, Zhao JX, Liu XY (2012) Successful treatment of SAPHO syndrome with severe spinal disorder using entercept: a case study. Rheumatol Int 32:1963–1965. CrossRefPubMedGoogle Scholar
  28. 28.
    Garcovich S, Amelia R, Magarelli N, Valenza V, Amerio P (2012) Long-term treatment of severe SAPHO syndrome with adalimumab. Am J Clin Dermatol 13:55–59. CrossRefPubMedGoogle Scholar
  29. 29.
    Burgemeister LT, Baeten DLP, Tas SW (2012) Biologics for rare inflammatory diseases: TNF blockade in the SAPHO syndrome. Neth J Med 70:444–449PubMedGoogle Scholar
  30. 30.
    Hampton SL, Youssef H (2013) Successful treatment of resistant SAPHO syndrome with anti-TNF therapy. BMJ Case Rep:2012–2014. Google Scholar
  31. 31.
    Naves JE, Cabré E, Mañosa M, Grados D, Olivé A, Domènech E (2013) A systematic review of SAPHO syndrome and inflammatory bowel disease association. Dig Dis Sci 58:2138–2147. CrossRefPubMedGoogle Scholar
  32. 32.
    Kundu BK, Naik AK, Bhargava S, Srivastava D (2013) Diagnosing the SAPHO syndrome: a report of three cases and review of literature. Clin Rheumatol 32:1237–1243. CrossRefPubMedGoogle Scholar
  33. 33.
    Kim CH, Kadhim S, Julien C (2014) Treatment of pain in SAPHO (synovitis, acne, Pustulosis, hyperostosis, and osteitis) syndrome. PM R 6:92–95. CrossRefPubMedGoogle Scholar
  34. 34.
    Abourazzak FE, Hachimi H, Kadi N, Berrada K, Tizniti S, Harzy T (2014) Etanercept in the treatment of SAPHO syndrome: which place? Eur J Rheumatol 1:125–128. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Marí A, Morla A, Melero M, Schiavone R, Rodríguez J (2014) Diffuse sclerosing osteomyelitis (DSO) of the mandible in SAPHO syndrome: a novel approach with anti-TNF therapy. Systematic review. J Cranio-Maxillofac Surg 42:1990–1996. CrossRefGoogle Scholar
  36. 36.
    Anić B, Padjen I, Mayer M et al (2014) Clinical features of the SAPHO syndrome and their role in choosing the therapeutic approach: report of four patients and review of the literature. Acta Dermatovenerol Croat 22:180–188PubMedGoogle Scholar
  37. 37.
    Sáez-Martín L-C, Gómez-Castro S, Román-Curto C, Palacios-Álvarez I, Fernández-López E (2015) Etanercept in the treatment of SAPHO syndrome. Int J Dermatol 54:e206–e208. CrossRefPubMedGoogle Scholar
  38. 38.
    Kamata Y, Minota S (2015) Successful treatment of a patient with SAPHO syndrome with certolizumab pegol. Rheumatol Int 35:1607–1608. CrossRefPubMedGoogle Scholar
  39. 39.
    Cotti E, Careddu R, Schirru E, Marongiu S, Barca MP, Manconi PE, Mercuro G (2015) A case of SAPHO syndrome with endodontic implications and treatment with biologic drugs. J Endod 41:1565–1570. CrossRefPubMedGoogle Scholar
  40. 40.
    Su YS, Chang CH (2015) SAPHO syndrome associated with acne conglobata successfully treated with etanercept. J Formos Med Assoc 114:562–564. CrossRefPubMedGoogle Scholar
  41. 41.
    Zhang L, Gao Z (2016) Etanercept in the treatment of refractory SAPHO syndrome. Am J Clin Exp Immunol 5:62–66PubMedPubMedCentralGoogle Scholar
  42. 42.
    Mateo L, Sanint J, Rodríguez Muguruza S, Martínez Morillo M, Pérez Andrés R, Domenech Puigcerver S (2017) Lesión osteolítica cervical como presentación del síndrome SAPHO. Reumatol Clin 13:44–47. CrossRefPubMedGoogle Scholar
  43. 43.
    Anić B, Padjen I, Barešić M, Težak S (2014) The lobster sign in SAPHO syndrome: unusually extensive osteitis of the anterior chest wall partially responsive to infliximab. Rheumatol Int 34:281–282. CrossRefPubMedGoogle Scholar
  44. 44.
    Cianci F, Zoli A, Gremese E, Ferraccioli G (2017) Clinical heterogeneity of SAPHO syndrome: challenging diagnose and treatment. Clin Rheumatol 36:2151–2158. CrossRefPubMedGoogle Scholar
  45. 45.
    Vekic DA, Woods J, Lin P, Cains GD (2018) SAPHO syndrome associated with hidradenitis suppurativa and pyoderma gangrenosum successfully treated with adalimumab and methotrexate: a case report and review of the literature. Int J Dermatol 57:10–18. CrossRefPubMedGoogle Scholar
  46. 46.
    Axmann R, Böhm C, Krönke G, Zwerina J, Smolen J, Schett G (2009) Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo. Arthritis Rheum 60:2747–2756. CrossRefPubMedGoogle Scholar
  47. 47.
    Morales-Múnera C, Vilarrasa E, Puig L (2013) Efficacy of ustekinumab in refractory palmoplantar pustular psoriasis. Br J Dermatol 168:820–824CrossRefGoogle Scholar
  48. 48.
    Kavanaugh A, Puig L, Gottlieb AB, Ritchlin C, You Y, Li S, Song M, Randazzo B, Rahman P, McInnes IB (2016) Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2). Ann Rheum Dis 75:1984–1988CrossRefGoogle Scholar
  49. 49.
    Li C, Wu X, Cao Y, Zeng Y, Zhang W, Zhang S, Liu Y, Jin H, Zhang W, Li L (2019) Paradoxical skin lesions induced by anti-TNF-α agents in SAPHO syndrome. Clin Rheumatol 38:53–61. CrossRefPubMedGoogle Scholar
  50. 50.
    Sarzi-Puttini P, Ceribelli A, Marotto D, Batticciotto A, Atzeni F (2019) Systemic rheumatic diseases: from biological agents to small molecules. Autoimmun Rev 18:583–592. CrossRefPubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Unidade de Doenças Auto-imunes/Serviço Medicina 7.2, Hospital de Curry CabralCentro Hospitalar Universitário de Lisboa CentralLisbonPortugal
  2. 2.Serviço de Medicina IVHospital de Santarém EPESantarémPortugal
  3. 3.Serviço de Medicina I, Unidade Local de Saúde do Baixo AlentejoHospital José Joaquim FernandesBejaPortugal
  4. 4.Serviço de Radiologia do Hospital de Curry CabralCentro Hospitalar Universitário de Lisboa CentralLisbonPortugal

Personalised recommendations