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SAPHO: has the time come for tailored therapy?

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Abstract

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.

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References

  1. Kahn M-F, Khan MA (1994) The SAPHO syndrome. Baillieres Clin Rheumatol 8:333–362. https://doi.org/10.1007/978-3-540-69375-8_77

    Article  CAS  PubMed  Google Scholar 

  2. Li C, Cao Y, Zhang W (2018) Clinical heterogeneity of SAPHO syndrome: challenge of diagnosis. Mod Rheumatol 28:432–434. https://doi.org/10.1080/14397595.2017.1416733

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1093/rheumatology/kew015

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1007/s11926-016-0583-y

  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. https://doi.org/10.2174/1871528113666140520100402

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.semarthrit.2018.04.003

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1093/rheumatology/keq074

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1136/annrheumdis-2011-200743

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1684/EJD.2016.2854

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.jbspin.2017.05.016

    Article  CAS  Google Scholar 

  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. https://doi.org/10.2169/internalmedicine.8473-16

    Article  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1111/bjd.16071

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1097/MD.0000000000011149

    Article  Google Scholar 

  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. https://doi.org/10.1002/art.10539

    Article  PubMed  Google Scholar 

  15. Ben Abdelghani K, Dran DG, Gottenberg JE et al (2010) Tumor necrosis factor-α blockers in SAPHO syndrome. J Rheumatol 37:1699–1704. https://doi.org/10.3899/jrheum.091086

    Article  CAS  PubMed  Google Scholar 

  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 90:301–302

    Article  Google Scholar 

  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. https://doi.org/10.1111/1756-185X.12525

    Article  CAS  PubMed  Google Scholar 

  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 61:375–376

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1016/j.jaad.2004.09.006

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1093/rheumatology/kei221

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1007/s10067-007-0767-y

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.semarthrit.2007.08.004

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1136/bcr.10.2008.1145

    Article  Google Scholar 

  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. https://doi.org/10.1007/s10067-010-1476-5

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.2340/00015555-0895

    Article  PubMed  Google Scholar 

  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 69:185–187

    PubMed  Google Scholar 

  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. https://doi.org/10.1007/s00296-011-1916-9

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.2165/11593250-000000000-00000

    Article  PubMed  Google Scholar 

  29. Burgemeister LT, Baeten DLP, Tas SW (2012) Biologics for rare inflammatory diseases: TNF blockade in the SAPHO syndrome. Neth J Med 70:444–449

    CAS  PubMed  Google Scholar 

  30. Hampton SL, Youssef H (2013) Successful treatment of resistant SAPHO syndrome with anti-TNF therapy. BMJ Case Rep:2012–2014. https://doi.org/10.1136/bcr-2012-007161

    Google Scholar 

  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. https://doi.org/10.1007/s10620-013-2653-6

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1007/s10067-013-2251-1

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.pmrj.2013.08.610

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.5152/eurjrheumatol.2014.037

    Article  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1016/j.jcms.2014.09.004

    Article  Google Scholar 

  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 22:180–188

    PubMed  Google Scholar 

  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. https://doi.org/10.1111/ijd.12675

    Article  PubMed  Google Scholar 

  38. Kamata Y, Minota S (2015) Successful treatment of a patient with SAPHO syndrome with certolizumab pegol. Rheumatol Int 35:1607–1608. https://doi.org/10.1007/s00296-015-3263-8

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.joen.2015.04.005

    Article  PubMed  Google Scholar 

  40. Su YS, Chang CH (2015) SAPHO syndrome associated with acne conglobata successfully treated with etanercept. J Formos Med Assoc 114:562–564. https://doi.org/10.1016/j.jfma.2013.10.001

    Article  PubMed  Google Scholar 

  41. Zhang L, Gao Z (2016) Etanercept in the treatment of refractory SAPHO syndrome. Am J Clin Exp Immunol 5:62–66

    PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1016/j.reuma.2015.11.016

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1007/s00296-012-2606-y

    Article  PubMed  Google Scholar 

  44. Cianci F, Zoli A, Gremese E, Ferraccioli G (2017) Clinical heterogeneity of SAPHO syndrome: challenging diagnose and treatment. Clin Rheumatol 36:2151–2158. https://doi.org/10.1007/s10067-017-3751-1

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1111/ijd.13740

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1002/art.24781

    Article  CAS  PubMed  Google Scholar 

  47. Morales-Múnera C, Vilarrasa E, Puig L (2013) Efficacy of ustekinumab in refractory palmoplantar pustular psoriasis. Br J Dermatol 168:820–824

    Article  Google Scholar 

  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 75:1984–1988

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1007/s10067-018-4083-5

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.autrev.2018.12.009

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Unidade de Doenças Auto-imunes/Serviço Medicina 7.2, Hospital de Curry Cabral, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal

    Adelaide Sofia Batalha Figueiredo, Ana Luísa Oliveira & Maria Francisca Moraes-Fontes

  2. Serviço de Medicina IV, Hospital de Santarém EPE, Av. Bernardo Santareno, 2005-177, Santarém, Portugal

    Adelaide Sofia Batalha Figueiredo

  3. Serviço de Medicina I, Unidade Local de Saúde do Baixo Alentejo, Hospital José Joaquim Fernandes, Beja, Portugal

    Ana Luísa Oliveira

  4. Serviço de Radiologia do Hospital de Curry Cabral, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal

    António Caetano

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  1. Adelaide Sofia Batalha Figueiredo
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  2. Ana Luísa Oliveira
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  3. António Caetano
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  4. Maria Francisca Moraes-Fontes
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Correspondence to Adelaide Sofia Batalha Figueiredo.

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Figueiredo, A.S.B., Oliveira, A.L., Caetano, A. et al. SAPHO: has the time come for tailored therapy?. Clin Rheumatol 39, 177–187 (2020). https://doi.org/10.1007/s10067-019-04675-2

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