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PAPA, PASH and PAPASH Syndromes: Pathophysiology, Presentation and Treatment

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Abstract

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis usually manifesting as skin ulcers with undermined erythematous-violaceous borders. It may be isolated, associated with systemic conditions or occurring in the context of autoinflammatory syndromes such as PAPA (pyogenic arthritis, PG and acne), PASH (PG, acne and suppurative hidradenitis) or PAPASH (pyogenic arthritis, acne, PG and suppurative hidradenitis). From a physiopathological point of view, all these conditions share common mechanisms consisting of over-activation of the innate immune system leading to increased production of the interleukin (IL)-1 family and ‘sterile’ neutrophil-rich cutaneous inflammation. From a genetic point of view, a number of mutations affecting the proteins of the inflammasome complex (the molecular platform responsible for triggering autoinflammation) or the proteins that regulate inflammasome function have been described in these disorders. As these debilitating entities are all associated with the over-expression of IL-1 and tumour necrosis factor (TNF)-α, biological drugs specifically targeting these cytokines are currently the most effective treatments but, given the emerging role of IL-17 in the pathogenesis of these syndromes, IL-17 antagonists may represent the future management of these conditions.

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References

  1. Wise CA, Gillum JD, Seidman CE, Lindor NM, Veile R, Bashiardes S, et al. Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet. 2002;11(8):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(3):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(3):215–9.

    Article  PubMed  Google Scholar 

  4. Marzano AV, Ceccherini I, Gattorno M, Fanoni D, Caroli F, Rusmini M, et al. Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases. Medicine (Baltimore). 2014;93(27):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(6):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(1):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(3):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(5):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  PubMed Central  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  PubMed  PubMed Central  Google Scholar 

  16. Marzano AV, Fanoni D, Antiga E, Quaglino P, Caproni M, Crosti C, et al. 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(1):48–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  18. Chen KW, Gross CJ, Sotomayor FV, Stacey KJ, Tschopp J, Sweet MJ, et al. The neutrophil NLRC4 inflammasome selectively promotes IL-1β 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, Takai S, Karin M, Corr M, 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, Rafail S, Chrysanthopoulou A, Speletas M, 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, et al. Keratinocytes and neutrophils are important sources of proinflammatory molecules in hidradenitis suppurativa. Br J Dermatol. 2016;174(3):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 three-dimensional 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;173:275–8.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  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, Seidman CE, McEvoy MT. 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, Zhang D, Gao X, Wood G, 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, Kerl K, Fettelschoss A, Feldmeyer L, et al. IL-1b 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, Krutzik SR, Garbán HJ, Kim J. Propionibacterium acnes induces IL-1b 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, Seo MS, Lee HE, Lee Y, 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, Cioschi S, Muratori F, D’Urbano LE, et al. Abnormal production of the tumour necrosis factor (TNF) 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, Aksentijevich I, Gallin JI, Turner ML, 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, Hull KM, Wood G, Wise CA, 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 USA. 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, 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, et al. 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, et al. Proline-serine-threonine phosphatase interacting protein 1 inhibition of T-cell receptor signaling depends on its SH3 domain. FEBS J. 2014;281(17):3844–54.

    Article  CAS  PubMed  Google Scholar 

  41. Cote JF, Chung PL, Theberge JF, Halle M, Spencer S, Lasky LA, et al. 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, et al. 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, et al. 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, et al. 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(1):91–3.

    Article  CAS  PubMed  Google Scholar 

  47. Smith EJ, Allantaz F, Bennett L, Zhang D, Gao X, Wood G, et al. Clinical, molecular, and genetic characteristics of PAPA syndrome: a review. Curr Genom. 2010;11(7):519–27.

    Article  CAS  Google Scholar 

  48. 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 

  49. Wise CA, Gillum JD, Seidman CE, Lindor NM, Veile R, Bashiardes S, et al. 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 

  50. Wang D, Höing S, Patterson HC, Ahmad UM, Rathinam VA, Rajewsky K, 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 

  51. Dovas A, Gevrey J-C, Grossi A, Park H, Abou-Kheir W, Cox D. 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 

  52. Monypenny J, Chou H-C, Bañón-Rodríguez I, Thrasher AJ, Antón IM, Jones GE, 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 

  53. Gawden-Bone C, Zhou Z, King E, Prescott A, Watts C, Lucocq J. 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 

  54. Starnes TW, Bennin DA, Bing X, Eickhoff JC, Grahf DC, Bellak JM, 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 

  55. Marzano AV, Ishak RS, Saibeni S, Crosti C, Meroni PL, Cugno M. 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 

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

    Article  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  60. 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 

  61. 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  Google Scholar 

  62. 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  Google Scholar 

  63. 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 

  64. 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  Google Scholar 

  65. 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 

  66. 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 

  67. 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 

  68. 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 

  69. 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 

  70. 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 

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

    Article  PubMed  Google Scholar 

  72. Lee H, Park SH, Kim SK, Choe JY, Park JS. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome) with E250 K mutation in CD2BP1 gene treated with the tumor necrosis factor inhibitor adalimumab. Clin Exp Rheumatol. 2012;30:452.

    CAS  PubMed  Google Scholar 

  73. 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 

  74. 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 

  75. 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 

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

    PubMed  Google Scholar 

  77. 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 

  78. Newman B, Cescon D, Domenchini A, Siminovitch KA. 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 

  79. Nesterovitch AB, Hoffman MD, Simon M, Petukhov PA, Tharp MD, Glant TT. 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 

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

    Article  PubMed  Google Scholar 

  81. Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, et al. ERASURE Study Group.; FIXTURE Study Group. Secukinumab in plaque psoriasis-results of two phase 3 trials. N Engl J Med. 2014;371(4):326–38.

    Article  PubMed  Google Scholar 

  82. Burkett PR, Kuchroo VK. IL-17 blockade in psoriasis. Cell. 2016;167(7):1669.

    Article  CAS  PubMed  Google Scholar 

  83. Chokoeva AA, Cardoso JC, Wollina U, Tchernev G. Pyoderma gangrenosum—a novel approach? Wien Med Wochenschr. 2016. doi:10.1007/s10354-016-0472-z (Epub 2016).

    Google Scholar 

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Authors and Affiliations

  1. Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Ospedale Maggiore Policlinico, Fondazione IRCCS Ca’ Granda, Via Pace, 9, 20122, Milan, Italy

    Massimo Cugno

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

    Alessandro Borghi

  3. 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 V. Marzano

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Massimo Cugno, Alessandro Borghi and Angelo V. Marzano declare that they have no conflicts of interest.

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Cugno, M., Borghi, A. & Marzano, A.V. PAPA, PASH and PAPASH Syndromes: Pathophysiology, Presentation and Treatment. Am J Clin Dermatol 18, 555–562 (2017). https://doi.org/10.1007/s40257-017-0265-1

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