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PAPA and Related Syndromes

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Neutrophilic Dermatoses

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Abstract

Pyoderma gangrenosum (PG) is a prototypical neutrophilic dermatosis that usually manifests itself in the form of cutaneous ulcers with undermined erythematous-violaceous borders. It may be isolated or associated with systemic conditions (i.e. inflammatory bowel diseases, rheumatological disorders and lymphoproliferation), or occur in the context of autoinflammatory syndromes such as PAPA (pyogenic arthritis, PG and acne) [1], PASH (PG, acne and suppurative hidradenitis) [2–4] or other more recently described syndromes such as PAPASH (pyogenic arthritis, acne, PG and suppurative hidradenitis) [5]. Autoinflammatory diseases (AIDs) are characterised by apparently unprovoked episodes of systemic inflammation in the absence of the typical features of autoimmunity, such as autoantibodies or antigen-specific T lymphocytes [6]. All of the autoinflammatory syndromes described here have the shared characteristic of skin involvement, hallmarked by an accumulation of neutrophils. Inflammatory conditions characterised by infiltrates mainly consisting of mature neutrophils without infection are defined as neutrophilic dermatoses. Originally, the main forms of neutrophilic dermatoses included prototypical conditions such as PG, Sweet’s syndrome, subcorneal pustular dermatosis, and erythema elevatum diutinum [7], but this list was subsequently extended to other diseases, including syndromic entities. From a pathophysiological point of view, these neutrophilic dermatoses present high levels of the same pro-inflammatory cytokines, chemokines and tissue damage effector molecules as those found in AIDs [8, 9]. Taken together, these aspects suggest that autoinflammatory syndromes and neutrophilic dermatoses have the common pathological mechanisms of an over-activated innate immune system leading to the increased production of the IL-1 family and “sterile” neutrophil-rich cutaneous inflammation. The autoinflammatory syndromes characterised by neutrophilic dermatoses therefore represent a model of integration between two conditions that can probably be considered “innate immune disorders” [6, 9].

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References

  1. Wise CA, Gillum JD, Seidman CE, Lindor NM, Veile R, Bashiardes S, Lovett M. Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet. 2002;11:961–9.

    Article  CAS  PubMed  Google Scholar 

  2. Braun-Falco M, Kovnerystyy O, Lohse P, Ruzicka T. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) - a new autoinflammatory syndrome distinct from PAPA syndrome. J Am Acad Dermatol. 2012;66:409–15.

    Article  PubMed  Google Scholar 

  3. Marzano AV, Ishak RS, Colombo A, Caroli F, Crosti C. Pyoderma gangrenosum, acne and suppurative hidradenitis syndrome following bowel bypass surgery. Dermatology. 2012;225:215–9.

    Article  PubMed  Google Scholar 

  4. Marzano AV, Ceccherini I, Gattorno M, Fanoni D, Caroli F, Rusmini M, Grossi A, De Simone C, Borghi OM, Meroni PL, Crosti C, Cugno M. Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases. Medicine (Baltimore). 2014;93:e187.

    Article  CAS  Google Scholar 

  5. Marzano AV, Trevisan V, Gattorno M, Ceccherini I, De Simone C, Crosti C. Pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH): a new autoinflammatory syndrome associated with a novel mutation of the PSTPIP1 gene. JAMA Dermatol. 2013;149:762–4.

    Article  PubMed  Google Scholar 

  6. Navarini AA, Satoh TK, French LE. Neutrophilic dermatoses and autoinflammatory diseases with skin involvement--innate immune disorders. Semin Immunopathol. 2016;38:45–56.

    Article  CAS  PubMed  Google Scholar 

  7. Wallach D. Les dermatoses neutrophiliques. (Editorial). Presse Med. 1991;20:105–7.

    CAS  PubMed  Google Scholar 

  8. Prat L, Bouaziz JD, Wallach D, Vignon-Pennamen MD, Bagot M. Neutrophilic dermatoses as systemic diseases. Clin Dermatol. 2014;32:376–88.

    Article  PubMed  Google Scholar 

  9. Marzano AV, Borghi A, Meroni PL, Cugno M. Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation. Br J Dermatol. 2016;175:882–91.

    Article  CAS  PubMed  Google Scholar 

  10. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood. 2011;117:3720–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009;27:519–50.

    Article  CAS  PubMed  Google Scholar 

  12. Saïd-Sadier N, Ojcius DM. Alarmins, inflammasomes and immunity. Biomed J. 2012;35:437–49.

    Article  PubMed  Google Scholar 

  13. Strowig T, Henao-Mejia J, Elinav E, Flavell R. Inflammasomes in health and disease. Nature. 2012;481:278–86.

    Article  CAS  PubMed  Google Scholar 

  14. Dinarello CA. A clinical perspective of IL-1β as the gatekeeper of inflammation. Eur J Immunol. 2011;41:1203–17.

    Article  CAS  PubMed  Google Scholar 

  15. Marzano AV, Cugno M, Trevisan V, Fanoni D, Venegoni L, Berti E, et al. Role of inflammatory cells, cytokines and matrix metalloproteinases in neutrophil-mediated skin diseases. Clin Exp Immunol. 2010;162:100–7.

    Article  CAS  Google Scholar 

  16. Marzano AV, Fanoni D, Antiga E, Quaglino P, Caproni M, Crosti C, Meroni PL, Cugno M. Expression of cytokines, chemokines and other effector molecules in two prototypic autoinflammatory skin diseases, pyoderma gangrenosum and Sweet’s syndrome. Clin Exp Immunol. 2014;178:48–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Mankan AK, Dau T, Jenne D, et al. The NLRP3/ASC/Caspase-1 axis regulates IL-1beta processing in neutrophils. Eur J Immunol. 2012;42:710–5.

    Article  CAS  PubMed  Google Scholar 

  18. Chen KW, Gross CJ, Sotomayor FV, et al. The neutrophil NLRC4 inflammasome selectively promotes IL-1beta maturation without pyroptosis during acute Salmonella challenge. Cell Rep. 2014;8:570–82.

    Article  CAS  PubMed  Google Scholar 

  19. Guma M, Ronacher L, Liu-Bryan R, et al. Caspase 1-independent activation of interleukin-1beta in neutrophil-predominant inflammation. Arthritis Rheum. 2009;60:3642–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mitroulis I, Kourtzelis I, Kambas K, et al. Regulation of the autophagic machinery in human neutrophils. Eur J Immunol. 2010;40:1461–72.

    Article  CAS  PubMed  Google Scholar 

  21. Lima AL, Karl I, Giner T, Poppe H, Schmidt M, Presser D, Goebeler M, Bauer B. Keratinocytes and neutrophils are important sources of proinflammatory molecules in hidradenitis suppurativa. Br J Dermatol. 2016;174:514–21.

    Article  CAS  PubMed  Google Scholar 

  22. Isailovic N, Daigo K, Mantovani A, Selmi C. Interleukin-17 and innate immunity in infections and chronic inflammation. J Autoimmun. 2015;60:1–11.

    Article  CAS  PubMed  Google Scholar 

  23. Donetti E, Cornaghi L, Gualerzi A, Baruffaldi Preis FW, Prignano F. An innovative threedimensional model of normal human skin to study the proinflammatory psoriatic effects of tumor necrosis factor-alpha and interleukin-17. Cytokine. 2014;68:1–8.

    Article  CAS  PubMed  Google Scholar 

  24. Caproni M, Antiga E, Volpi W, Verdelli A, Venegoni L, Quaglino P, et al. The Treg/Th17 cell ratio is reduced in the skin lesions of patients with pyoderma gangrenosum. Br J Dermatol. 2015;73:275–8.

    Article  Google Scholar 

  25. Foster AM, Baliwag J, Chen CS, et al. IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin. J Immunol. 2014;192:6053–61.

    Article  CAS  PubMed  Google Scholar 

  26. Agarwal S, Misra R, Aggarwal A. Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metalloproteinases. J Rheumatol. 2008;35:515–9.

    CAS  PubMed  Google Scholar 

  27. Lindor NM, Arsenault TM, Solomon H, et al. A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum and acne: PAPA syndrome. Mayo Clin Proc. 1997;72:611–5.

    Article  CAS  PubMed  Google Scholar 

  28. Naik HB, Cowen EW. Autoinflammatory pustular neutrophilic diseases. Dermatol Clin. 2013;31:405–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tallon B, Corkill M. Peculiarities of PAPA syndrome. Rheumatology. 2006;45:1140–3.

    Article  CAS  PubMed  Google Scholar 

  30. Smith EJ, Allantaz F, Bennett L, et al. Clinical, molecular, and genetic characteristics of PAPA syndrome: a review. Curr Genomics. 2010;11:519–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Callen JP. Pyoderma gangrenosum. Lancet. 1996;351:581–5.

    Article  Google Scholar 

  32. Kistowska M, Gehrke S, Jankovic D, et al. IL-1β drives inflammatory responses to Propionibacterium acnes in vitro and in vivo. J Invest Dermatol. 2014;134:677–85.

    Article  CAS  PubMed  Google Scholar 

  33. Qin M, Pirouz A, Kim MH, et al. Propionibacterium acnes induces IL-1β secretion via the NLRP3 inflammasome in human monocytes. J Invest Dermatol. 2014;134:381–8.

    Article  CAS  PubMed  Google Scholar 

  34. Li ZJ, Choi DK, Sohn KC, et al. Propionibacterium acnes activates the NLRP3 inflammasome in human sebocytes. J Invest Dermatol. 2014;134:2747–56.

    Article  CAS  PubMed  Google Scholar 

  35. Cortis E, De Benedetti F, Insalaco A, et al. Abnormal production of the tumour necrosis factor alpha and clinical efficacy of the TNF inhibitor etanercept in a patient with PAPA syndrome. J Pediatr. 2004;145:851–5.

    Article  PubMed  Google Scholar 

  36. Demidowich AP, Freeman AF, Kuhns DB, et al. Brief report: genotype, phenotype, and clinical course in five patients with PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne). Arthritis Rheum. 2012;64:2022–7.

    Article  PubMed  Google Scholar 

  37. Shoham NG, Centola M, Mansfield E, et al. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. Proc Natl Acad Sci U S A. 2003;100:13501–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Shimada A, Niwa H, Tsujita K, Suetsugu S, Nitta K, Hanawa-Suetsugu K, Akasaka R, Nishino Y, Toyama M, Chen L, et al. Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis. Cell. 2007;129:761–72.

    Article  CAS  PubMed  Google Scholar 

  39. Henne WM, Kent HM, Ford MG, Hegde BG, Daumke O, Butler PJ, Mittal R, Langen R, Evans PR, McMahon HT. Structure and analysis of FCHo2 F-BAR domain: a dimerizing and membrane recruitment module that effects membrane curvature. Structure. 2007;15:839–52.

    Article  CAS  PubMed  Google Scholar 

  40. Marcos T, Ruiz-Martín V, de la Puerta ML, Trinidad AG, Rodríguez Mdel C, de la Fuente MA, Sánchez Crespo M, Alonso A, Bayón Y. Proline-serine-threonine phosphatase interacting protein 1 inhibition of T-cell receptor signaling depends on its SH3 domain. FEBS J. 2014;281:3844–54.

    Article  CAS  PubMed  Google Scholar 

  41. Cote JF, Chung PL, Theberge JF, Halle M, Spencer S, Lasky LA, Tremblay ML. PSTPIP is a substrate of PTP-PEST and serves as a scaffold guiding PTP-PEST toward a specific dephosphorylation of WASP. J Biol Chem. 2002;277:2973–86.

    Article  CAS  PubMed  Google Scholar 

  42. Badour K, Zhang J, Shi F, McGavin MK, Rampersad V, Hardy LA, Field D, Siminovitch KA. The Wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP and PSTPIP1 adaptors to promote formation of the immunological synapse. Immunity. 2003;18:141–54.

    Article  CAS  PubMed  Google Scholar 

  43. Wu Y, Spencer SD, Lasky LA. Tyrosine phosphorylation regulates the SH3-mediated binding of the Wiskott-Aldrich syndrome protein to PSTPIP, a cytoskeletal-associated protein. J Biol Chem. 1998;273:5765–70.

    Article  CAS  PubMed  Google Scholar 

  44. Cong F, Spencer S, Cote JF, Wu Y, Tremblay ML, Lasky LA, Goff SP. Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl dephosphorylation. Mol Cell. 2000;6:1413–23.

    Article  CAS  PubMed  Google Scholar 

  45. Li J, Nishizawa K, An W, Hussey RE, Lialios FE, Salgia R, Sunder-Plassmann R, Reinherz EL. A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic domain and regulates CD2-triggered adhesion. EMBO J. 1998;17:7320–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lindwall E, Singla S, Davis WE, Quinet RJ. Novel PSTPIP1 gene mutation in a patient with pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome. Semin Arthritis Rheum. 2015;45:91–3.

    Article  CAS  PubMed  Google Scholar 

  47. Yeon HB, Lindor HM, Seidman JG, Seidman CE. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome maps to chromosome 15q. Am J Hum Genet. 2000;66:1443–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wang D, Höing S, Patterson HC, et al. Inflammation in mice ectopically expressing human pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome-associated PSTPIP1 A230T mutant proteins. J Biol Chem. 2013;288:4594–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Dovas A, Gevrey J-C, Grossi A, et al. Regulation of podosome dynamics by WASp phosphorylation: implication in matrix degradation and chemotaxis in macrophages. J Cell Sci. 2009;122:3873–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Monypenny J, Chou H-C, Banon-Rodriguez I, et al. Role of WASP in cell polarity and podosome dynamics of myeloid cells. Eur J Cell Biol. 2011;90:198–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gawden-Bone C, Zhou Z, King E, et al. Dendritic cell podosomes are protrusive and invade the extracellular matrix using metalloproteinase MMP-14. J Cell Sci. 2010;123:1427–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Starnes TW, Bennin DA, Bing X, et al. The F-BAR protein PSTPIP1 controls extracellular matrix degradation and filopodia formation in macrophages. Blood. 2014;123:2703–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Marzano AV, Ishak RS, Saibeni S, et al. Autoinflammatory skin disorders in inflammatory bowel diseases, pyoderma gangrenosum and Sweet’s syndrome: a comprehensive review and disease classification criteria. Clin Rev Allergy Immunol. 2013;45:202–10.

    Article  CAS  PubMed  Google Scholar 

  54. Almeida de Jesus A, Goldbach-Mansky R. Monogenic autoinflammatory diseases: concept and clinical manifestations. Clin Immunol. 2013;147:155–74.

    Article  CAS  PubMed  Google Scholar 

  55. Wollina U, Haroske G. Pyoderma gangrenosum. Curr Opin Rheumatol. 2011;23:50–6.

    Article  PubMed  Google Scholar 

  56. Dessinioti C, Katsambas A, Antoniou C. Hidradenitis suppurativa (acne inversa) as a systemic disease. Clin Dermatol. 2014;32:397–408.

    Article  PubMed  Google Scholar 

  57. Jemec GB. Clinical practice. Hidradenitis suppurativa. N Engl J Med. 2012;366:158–64.

    Article  CAS  PubMed  Google Scholar 

  58. Duchatelet S, Miskinyte S, Join-Lambert O, Ungeheuer MN, Francès C, Nassif A, et al. First nicastrin mutation in PASH (pyoderma gangrenosum, acne and suppurative hidradenitis) syndrome. Br J Dermatol. 2015;173:610–2.

    Article  CAS  PubMed  Google Scholar 

  59. Calderón-Castrat X, Bancalari-Diaz D, Román-Curto C, Romo-Melgar A, Amorós-Cerdán D, Alcaraz-Mas L, et al. PSTPIP1 Gene mutation in a pyoderma gangrenosum, acne and suppurative hidradenitis (PASH) syndrome. Br J Dermatol. 2016;175:194–8.

    Article  PubMed  CAS  Google Scholar 

  60. André MF, Aumaître O, Grateau G, Chamaillard M, Costedoat-Chalumeau N, Cardoso MC, et al. Longest form of CCTG microsatellite repeat in the promoter of the CD2BP1/PSTPIP1 gene is associated with aseptic abscesses and with Crohn disease in French patients. Dig Dis Sci. 2010;55:1681–8.

    Article  PubMed  CAS  Google Scholar 

  61. Hampe J, Grebe J, Nikolaus S, Solberg C, Croucher PJ, Mascheretti S, et al. Association of NOD2 (CARD 15) genotype with clinical course of Crohn’s disease: a cohort study. Lancet. 2002;359:1661–5.

    Article  CAS  PubMed  Google Scholar 

  62. Pink AE, Simpson MA, Desai N, Trembath RC, Barker JN. γ-Secretase mutations in hidradenitis suppurativa: new insights into disease pathogenesis. J Invest Dermatol. 2012;133:601–7.

    Article  PubMed  CAS  Google Scholar 

  63. Wehrli P, Viard L, Bullani R, Tschopp J, French LE. Death receptors in cutaneous biology and disease. J Invest Dermatol. 2000;115:141–8.

    Article  CAS  PubMed  Google Scholar 

  64. Danese S, Sans M, Fiocchi C. The CD40/CD40L costimulatory pathway in inflammatory bowel disease. Gut. 2004;53:1035–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kahn MF, Khan MA. The SAPHO syndrome. Baillieres Clin Rheumatol. 1994;8:333–62.

    Article  CAS  PubMed  Google Scholar 

  66. Nguyen MT, Borchers A, Selmi C, et al. The SAPHO syndrome. Semin Arthritis Rheum. 2012;42:254–65.

    Article  PubMed  Google Scholar 

  67. Carneiro S, Sampaio-Barros PD. SAPHO syndrome. Rheum Dis Clin N Am. 2013;39:401–18.

    Article  Google Scholar 

  68. Kundu BK, Naik AK, Bhargava S, Srivastava D. Diagnosing the SAPHO syndrome: a report of three cases and review of literature. Clin Rheumatol. 2013;32:1237–43.

    Article  PubMed  Google Scholar 

  69. Colina M, Govoni M, Orzincolo C, Trotta F. Clinical and radiologic evolution of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: a single center study of a cohort of 71 subjects. Arthritis Rheum. 2009;61:813–21.

    Article  PubMed  Google Scholar 

  70. Richette P, Molto A, Viguier M, et al. Hidradenitis suppurativa associated with spondyloarthritis – results from a multicentre national prospective study. J Rheumatol. 2014;41:490–4.

    Article  PubMed  Google Scholar 

  71. Claudepierre P, Clerc D, Cariou D, et al. SAPHO syndrome and pyoderma gangrenosum: is it fortuitous? J Rheumatol. 1996;23:400–2.

    CAS  PubMed  Google Scholar 

  72. Naves JE, Cabré E, Mañosa M, et al. A systematic review of SAPHO syndrome and inflammatory bowel disease association. Dig Dis Sci. 2013;58:2138–47.

    Article  CAS  PubMed  Google Scholar 

  73. Rukavina I. SAPHO syndrome: a review. J Child Orthop. 2015;9:19–27.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Assmann G, Simon P. The SAPHO syndrome – are microbes involved? Best Pract Res Clin Rheumatol. 2011;25:423–34.

    Article  CAS  PubMed  Google Scholar 

  75. Hurtado-Nedelec M, Chollet-Martin S, Nicaise-Roland P, et al. Characterization of the immune response in the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Rheumatology (Oxford). 2008;47:1160–7.

    Article  CAS  Google Scholar 

  76. Hofmann SR, Morbach H, Schwarz T, Rosen-Wolff A, Girschick HJ, Hedrich CM. Attenuated TLR4/MAPK signaling in monocytes from patients with CRMO results in impaired IL-10 expression. Clin Immunol. 2012;145:69–76.

    Article  CAS  PubMed  Google Scholar 

  77. Lopalco G, Cantarini L, Vitale A, et al. Interleukin-1 as a common denominator from autoinflammatory to autoimmune disorders: premises, perils, and perspectives. Mediat Inflamm. 2015;2015:194864.

    Article  CAS  Google Scholar 

  78. Killeen ME, Ferris L, Kupetsky EA, et al. Signaling through purinergic receptors for ATP induces human cutaneous innate and adaptive Th17 responses: implications in the pathogenesis of psoriasis. J Immunol. 2013;190:4324–36.

    Article  CAS  PubMed  Google Scholar 

  79. Firinu D, Barca MP, Lorrai MM, et al. TH17 cells are increased in the peripheral blood of patients with SAPHO syndrome. Autoimmunity. 2014;47:389–94.

    Article  CAS  PubMed  Google Scholar 

  80. Golla A, Jansson A, Ramser J, et al. Chronic recurrent multifocal osteomyelitis (CRMO): evidence for a susceptibility gene located on chromosome 18q21.3–18q22. Eur J Hum Genet. 2002;10:217–21.

    Article  PubMed  Google Scholar 

  81. Hurtado-Nedelec M, Chollet-Martin S, Chapeton D, et al. Genetic susceptibility factors in a cohort of 38 patients with SAPHO syndrome: a study of PSTPIP2, NOD2, and LPIN2 genes. J Rheumatol. 2010;37:401–9.

    Article  CAS  PubMed  Google Scholar 

  82. Burgemeister LT, Baeten DL, Tas SW. Biologics for rare inflammatory diseases: TNF blockade in the SA PHO syndrome. Neth J Med. 2012;70:444–9.

    CAS  PubMed  Google Scholar 

  83. Jesus AA, Goldbach-Mansky R. IL-1 blockade in autoinflammatory syndromes. Annu Rev Med. 2014;65:223–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Assmann G, Wagner AD, Monika M, Pfoehler C, Pfreundschuh M, Tilgen W, et al. Single-nucleotide polymorphisms p53 G72C and Mdm2 T309G in patients with psoriasis, psoriatic arthritis, and SAPHO syndrome. Rheumatol Int. 2010;30:1273–6.

    Article  CAS  PubMed  Google Scholar 

  85. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Govoni M, Colina M, Massara A, Trotta F. SAPHO syndrome and infections. Autoimmun Rev. 2009;8:256–9.

    Article  CAS  PubMed  Google Scholar 

  87. Girschick HJ, Huppertz HI, Harmsen D, Krauspe R, Müller-Hermelink HK, Papadopoulos T. Chronic recurrent multifocal osteomyelitis in children: diagnostic value of histopathology and microbial testing. Hum Pathol. 1999;30:59–65.

    Article  CAS  PubMed  Google Scholar 

  88. Job-Deslandre C, Krebs S, Kahan A. Chronic recurrent multifocal osteomyelitis: five-year outcomes in 14 pediatric cases. Joint Bone Spine. 2001;68:245–51.

    Article  CAS  PubMed  Google Scholar 

  89. Bruzzese V. Pyoderma gangrenosum, acne conglobata, suppurative hidradenitis, and axial spondyloarthritis: efficacy of anti-tumor necrosis factor α therapy. J Clin Rheumatol. 2012;18:413–5.

    Article  PubMed  Google Scholar 

  90. Garzorz N, Papanagiotou V, Atenhan A, Andres C, Eyerich S, Eyerich K, et al. Pyoderma gangrenosum, acne, psoriasis, arthritis and suppurative hidradenitis (PAPASH)-syndrome: a new entity within the spectrum of autoinflammatory syndromes? J Eur Acad Dermatol Venereol. 2016;30:141–3.

    Article  CAS  PubMed  Google Scholar 

  91. Saraceno R, Babino G, Chiricozzi A, Zangrilli A, Chimenti S. PsAPASH: a new syndrome associated with hidradenitis suppurativa with response to tumor necrosis factor inhibition. J Am Acad Dermatol. 2015;72:e42–4.

    Article  PubMed  Google Scholar 

  92. Stichweh DS, Punaro M, Pascual V. Dramatic improvement of pyoderma gangrenosum with infliximab in a patient with PAPA syndrome. Pediatr Dermatol. 2005;22:262–5.

    Article  PubMed  Google Scholar 

  93. Tofteland ND, Shaver TS. Clinical efficacy of etanercept for treatment of PAPA syndrome. J Clin Rheumatol. 2010;16:244–5.

    Article  PubMed  Google Scholar 

  94. Lee H, Park SH, Kim SK, Choe JY, Park JS. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome) with E250K mutation in CD2BP1 gene treated with the tumor necrosis factor inhibitor adalimumab. Clin Exp Rheumatol. 2012;30:452.

    CAS  PubMed  Google Scholar 

  95. Brenner M, Ruzicka T, Plewig G, Thomas P, Herzer P. Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra. Br J Dermatol. 2009;161:1199–201.

    Article  CAS  PubMed  Google Scholar 

  96. Dierselhuis MP, Frenkel J, Wulffraat NM, Boelens JJ. Anakinra for flares of pyogenic arthritis in PAPA syndrome. Rheumatology (Oxford). 2005;44:406–8.

    Article  CAS  Google Scholar 

  97. Staub J, Pfannschmidt N, Strohal R, Braun-Falco M, Lohse P, Goerdt S, et al. Successful treatment of PASH syndrome with infliximab, cyclosporine and dapsone. J Eur Acad Dermatol Venereol. 2015;29:2243–7.

    Article  CAS  PubMed  Google Scholar 

  98. Scheinfeld N. Diseases associated with hidradenitis suppurativa: part 2 of a series on hidradenitis. Dermatol Online J. 2013;19:18558.

    PubMed  Google Scholar 

  99. Dinarello CA, van der Meer JW. Treating inflammation by blocking interleukin-1 in humans. Semin Immunol. 2013;25:469–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Jung J, Molinger M, Kohn D, et al. Intra-articular glucocorticosteroid injection into sternocostoclavicular joints in patients with SAPHO syndrome. Semin Arthritis Rheum. 2012;42:266–70.

    Article  CAS  PubMed  Google Scholar 

  101. Hayama K, Inadomi T, Fujisawa D, Terui T. A pilot study of medium-dose cyclosporine for the treatment of palmoplantar pustulosis complicated with pustulotic arthro-osteitis. Eur J Dermatol. 2010;20:758–62.

    CAS  PubMed  Google Scholar 

  102. Amital H, Applbaum YH, Aamar S, et al. SAPHO syndrome treated with pamidronate: an open-label study of 10 patients. Rheumatology (Oxford). 2004;43:658–61.

    Article  CAS  Google Scholar 

  103. Firinu D, Murgia G, Lorrai MM, Barca MP, Peralta MM, Manconi PE, et al. Biological treatments for SAPHO syndrome: an update. Inflamm Allergy Drug Targets. 2014;13:199–205.

    Article  CAS  PubMed  Google Scholar 

  104. Olivieri I, Padula A, Ciancio G, Salvarani C, Niccoli L, Cantini F. Successful treatment of SAPHO syndrome with infliximab: report of two cases. Ann Rheum Dis. 2002;61:375–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Wagner AD, Andresen J, Jendro MC, Hulsemann JL, Zeidler H. Sustained response to tumor necrosis factor alpha-blocking agents in two patients with SAPHO syndrome. Arthritis Rheum. 2002;46:1965–8.

    Article  PubMed  Google Scholar 

  106. Wendling D, Prati C, Aubin F. Anakinra treatment of SAPHO syndrome: short-term results of an open study. Ann Rheum Dis. 2012;71:1098–100.

    Article  CAS  PubMed  Google Scholar 

  107. Colina M, Pizzirani C, Khodeir M, Falzoni S, Bruschi M, Trotta F, et al. Dysregulation of P2X7 receptor-inflammasome axis in SAPHO syndrome: successful treatment with anakinra. Rheumatology (Oxford). 2010;49:1416–8.

    Article  CAS  Google Scholar 

  108. Newman B, Cescon D, Domenchini A, et al. CD2BP1 and CARD15 mutations are not associated with pyoderma gangrenosum in patients with inflammatory bowel disease. J Invest Dermatol. 2004;122:1054–6.

    Article  CAS  PubMed  Google Scholar 

  109. Nesterovitch AB, Hoffman MD, Simon M, et al. Mutations in the PSTPIP1 gene and aberrant splicing variants in patients with pyoderma gangrenosum. Clin Exp Dermatol. 2011;36:889–95.

    Article  CAS  PubMed  Google Scholar 

  110. Guenova E, Teske A, Fehrenbacher B, et al. Interleukin 23 expression in pyoderma gangrenosum and targeted therapy with ustekinumab. Arch Dermatol. 2011;147:1203–5.

    Article  PubMed  Google Scholar 

  111. Hamel J, Paul D, Gahr M, Hedrich CM. Pilot study: possible association of IL10 promoter polymorphisms with CRMO. Rheumatol Int. 2012;32:555–6.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Unità Operativa di Dermatologia, IRCCS Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

    Angelo Valerio Marzano

  2. Dipartimento di Scienze Mediche, Sezione di Dermatologia e Malattie Infettive, Università degli Studi di Ferrara, Ferrara, Italy

    Alessandro Borghi

  3. Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, IRCCS Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

    Massimo Cugno

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  1. Angelo Valerio Marzano
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  2. Alessandro Borghi
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  3. Massimo Cugno
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Correspondence to Angelo Valerio Marzano .

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Editors and Affiliations

  1. Physician (Hon.) of Paris Hospitals, Paris, France

    Daniel Wallach

  2. Pathology Department, APHP Hôpital Saint Louis, Paris, France

    Marie-Dominique Vignon-Pennamen

  3. Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universita’ degli Studi di Milano, Unita’ Operativa di Dermatologia, IRCCS Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy

    Angelo Valerio Marzano

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Marzano, A.V., Borghi, A., Cugno, M. (2018). PAPA and Related Syndromes. In: Wallach, D., Vignon-Pennamen, MD., Valerio Marzano, A. (eds) Neutrophilic Dermatoses. Springer, Cham. https://doi.org/10.1007/978-3-319-72649-6_14

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