Autoinflammatory Disorders: A Review and Update on Pathogenesis and Treatment

  • Annika Havnaer
  • George HanEmail author
Review Article


The autoinflammatory diseases comprise a broad spectrum of disorders characterized by unchecked activation of the innate immune system. Whereas aberrations in adaptive immunity have long been identified in ‘autoimmune’ disorders, the concept of ‘autoinflammation’ emerged relatively recently, first describing a group of clinical disorders characterized by spontaneous episodes of systemic inflammation without manifestations typical of autoimmune disorders. Improved knowledge of innate immune mechanisms, coupled with remarkable progress in genomics and an expanding number of clinical cases, has since led to an increasing number of disorders classified as autoinflammatory or containing an autoinflammatory component. Biologic therapies targeting specific components of the innate immune system have provided immense clinical benefit, and have further elucidated the role of innate immunity in autoinflammatory disorders. This article reviews the basic mechanisms of autoinflammation, followed by an update on the pathophysiology and treatment of the monogenic and multifactorial autoinflammatory diseases, and the common dermatologic conditions in which autoinflammation plays a major role.


Compliance with Ethical Standards


No funding was received for the preparation of this review.

Conflict of interest

Annika Havnaer and George Han declare no conflicts of interest.


  1. 1.
    Sidiropoulos PI, Goulielmos G, Voloudakis GK, Petraki E, Boumpas DT. Inflammasomes and rheumatic diseases: evolving concepts. Ann Rheum Dis. 2008;67(10):1382–9. Scholar
  2. 2.
    Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002;10(2):417–26.CrossRefPubMedGoogle Scholar
  3. 3.
    Deuteraiou K, Kitas G, Garyfallos A, Dimitroulas T. Novel insights into the role of inflammasomes in autoimmune and metabolic rheumatic diseases. Rheumatol Int. 2018;38(8):1345–54. Scholar
  4. 4.
    Das M, Kaveri SV, Bayry J. Cross-presentation of antigens by dendritic cells: role of autophagy. Oncotarget. 2015;6(30):28527–8. Scholar
  5. 5.
    Schmid D, Munz C. Immune surveillance of intracellular pathogens via autophagy. Cell Death Diff. 2005;12(Suppl 2):1519–27. Scholar
  6. 6.
    Ireland JM, Unanue ER. Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells. J Exp Med. 2011;208(13):2625–32. Scholar
  7. 7.
    Fulda S. Targeting apoptosis for anticancer therapy. Semin Cancer Biol. 2015;31:84–8. Scholar
  8. 8.
    Beeson PB. Temperature-elevating effect of a substance obtained from polymorphonuclear leucocytes. J Clin Investig. 1948;27(4):524.PubMedGoogle Scholar
  9. 9.
    Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11(8):633–52. Scholar
  10. 10.
    Vidal-Vanaclocha F, Fantuzzi G, Mendoza L, Fuentes AM, Anasagasti MJ, Martin J, et al. IL-18 regulates IL-1beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. Proc Natl Acad Sci USA. 2000;97(2):734–9.CrossRefGoogle Scholar
  11. 11.
  12. 12.
    FDA. US rilonacept label. In: FDA, editor. 2008.
  13. 13.
    FDA. US canakinumab label. In: FDA, editor. 2016.
  14. 14.
    Torrelo A. CANDLE syndrome as a paradigm of proteasome-related autoinflammation. Front Immunol. 2017;8:927. Scholar
  15. 15.
    Seifert U, Bialy LP, Ebstein F, Bech-Otschir D, Voigt A, Schroter F, et al. Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress. Cell. 2010;142(4):613–24. Scholar
  16. 16.
    Touitou I. The spectrum of familial Mediterranean fever (FMF) mutations. Eur J Hum Genet EJHG. 2001;9(7):473–83. Scholar
  17. 17.
    Brenner-Ullman A, Melzer-Ofir H, Daniels M, Shohat M. Possible protection against asthma in heterozygotes for familial Mediterranean fever. Am J Med Genet. 1994;53(2):172–5. Scholar
  18. 18.
    The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell. 1997;90(4):797–807.Google Scholar
  19. 19.
    Sohar E, Gafni J, Pras M, Heller H. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med. 1967;43(2):227–53.CrossRefPubMedGoogle Scholar
  20. 20.
    Barzilai A, Langevitz P, Goldberg I, Kopolovic J, Livneh A, Pras M, et al. Erysipelas-like erythema of familial Mediterranean fever: clinicopathologic correlation. J Am Acad Dermatol. 2000;42(5 Pt 1):791–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Braun-Falco M, Ruzicka T. Skin manifestations in autoinflammatory syndromes. Journal der Deutschen Dermatologischen Gesellschaft J Ger Soc Dermatol. 2011;9(3):232–46. Scholar
  22. 22.
    Ozdogan H, Arisoy N, Kasapcapur O, Sever L, Caliskan S, Tuzuner N, et al. Vasculitis in familial Mediterranean fever. J Rheumtol. 1997;24(2):323–7.Google Scholar
  23. 23.
    Gershoni-Baruch R, Broza Y, Brik R. Prevalence and significance of mutations in the familial Mediterranean fever gene in Henoch-Schonlein purpura. J Pediatr. 2003;143(5):658–61. Scholar
  24. 24.
    Chae JJ, Wood G, Masters SL, Richard K, Park G, Smith BJ, et al. The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci USA. 2006;103(26):9982–7. Scholar
  25. 25.
    Wang DQH, Bonfrate L, de Bari O, Wang TY, Portincasa P. Familial Mediterranean fever: from pathogenesis to treatment. J Genet Syndr Gene Ther. 2014;5:248. Scholar
  26. 26.
    Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni J. Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N Engl J Med. 1986;314(16):1001–5. Scholar
  27. 27.
    Cronstein BN, Molad Y, Reibman J, Balakhane E, Levin RI, Weissmann G. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. J Clin Investig. 1995;96(2):994–1002. Scholar
  28. 28.
    Park YH, Wood G, Kastner DL, Chae JJ. Pyrin inflammasome activation and RhoA signaling in the autoinflammatory diseases FMF and HIDS. Nat Immunol. 2016;17(8):914–21. Scholar
  29. 29.
    Ben-Chetrit E, Bergmann S, Sood R. Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis. Rheumatology (Oxford, England). 2006;45(3):274–82. Scholar
  30. 30.
    Cerquaglia C, Diaco M, Nucera G, La Regina M, Montalto M, Manna R. Pharmacological and clinical basis of treatment of familial Mediterranean fever (FMF) with colchicine or analogues: an update. Curr Drug Targets Inflamm Allergy. 2005;4(1):117–24.CrossRefPubMedGoogle Scholar
  31. 31.
    Ben-Zvi I, Kukuy O, Giat E, Pras E, Feld O, Kivity S, et al. Anakinra for colchicine-resistant familial Mediterranean fever: a randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol (Hoboken, NJ). 2017;69(4):854–62. Scholar
  32. 32.
    van der Hilst J, Moutschen M, Messiaen PE, Lauwerys BR, Vanderschueren S. Efficacy of anti-IL-1 treatment in familial Mediterranean fever: a systematic review of the literature. Biol Targets Ther. 2016;10:75–80. Scholar
  33. 33.
    Akar S, Cetin P, Kalyoncu U, Karadag O, Sari I, Cinar M, et al. Nationwide experience with off-label use of interleukin-1 targeting treatment in familial Mediterranean fever patients. Arthritis Care Res. 2018;70(7):1090–4. Scholar
  34. 34.
    Ozen S, Demirkaya E, Erer B, Livneh A, Ben-Chetrit E, Giancane G, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis. 2016;75(4):644–51. Scholar
  35. 35.
    Hentgen V, Grateau G, Kone-Paut I, Livneh A, Padeh S, Rozenbaum M, et al. Evidence-based recommendations for the practical management of familial Mediterranean fever. Semin Arthritis Rheum. 2013;43(3):387–91. Scholar
  36. 36.
    De Benedetti F, Gattorno M, Anton J, Ben-Chetrit E, Frenkel J, Hoffman HM, et al. Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. N Engl J Med. 2018;378(20):1908–19. Scholar
  37. 37.
    Laskari K, Boura P, Dalekos GN, Garyfallos A, Karokis D, Pikazis D, et al. Longterm beneficial effect of canakinumab in colchicine-resistant familial Mediterranean fever. J Rheumtol. 2017;44(1):102–9. Scholar
  38. 38.
    Hashkes PJ, Spalding SJ, Giannini EH, Huang B, Johnson A, Park G, et al. Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial. Ann Intern Med. 2012;157(8):533–41. Scholar
  39. 39.
    Ozgocmen S, Akgul O. Anti-TNF agents in familial Mediterranean fever: report of three cases and review of the literature. Mod Rheumatol. 2011;21(6):684–90. Scholar
  40. 40.
    Ozcakar ZB, Yuksel S, Ekim M, Yalcinkaya F. Infliximab therapy for familial Mediterranean fever-related amyloidosis: case series with long term follow-up. Clin Rheumatol. 2012;31(8):1267–71. Scholar
  41. 41.
    Bilgen SA, Kilic L, Akdogan A, Kiraz S, Kalyoncu U, Karadag O, et al. Effects of anti-tumor necrosis factor agents for familial Mediterranean fever patients with chronic arthritis and/or sacroiliitis who were resistant to colchicine treatment. J Clin Rheumatol. 2011;17(7):358–62. Scholar
  42. 42.
    Marzano AV, Damiani G, Genovese G, Gattorno M. A dermatologic perspective on autoinflammatory diseases. Clini Exp Rheumatol. 2018;36 Suppl 110(1):32–8.Google Scholar
  43. 43.
    Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet. 2001;29(3):301–5. Scholar
  44. 44.
    Aksentijevich I, Nowak M, Mallah M, Chae JJ, Watford WT, Hofmann SR, et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum. 2002;46(12):3340–8. Scholar
  45. 45.
    Infevers. Infevers: an online database for autoinflammatory mutations. 2018. Accessed 9 Nov 2018.
  46. 46.
    Lee GS, Subramanian N, Kim AI, Aksentijevich I, Goldbach-Mansky R, Sacks DB, et al. The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2 + and cAMP. Nature. 2012;492(7427):123–7. Scholar
  47. 47.
    Ito S, Hara Y, Kubota T. CARD8 is a negative regulator for NLRP3 inflammasome, but mutant NLRP3 in cryopyrin-associated periodic syndromes escapes the restriction. Arthritis Res Ther. 2014;16(1):R52. Scholar
  48. 48.
    Krause K, Grattan CE, Bindslev-Jensen C, Gattorno M, Kallinich T, de Koning HD, et al. How not to miss autoinflammatory diseases masquerading as urticaria. Allergy. 2012;67(12):1465–74. Scholar
  49. 49.
    Autoinflammatory Alliance. Muckle-Wells syndrome (MWS). 2017. Accessed 30 Oct 2018.
  50. 50.
    Goldbach-Mansky R. Current status of understanding the pathogenesis and management of patients with NOMID/CINCA. Curr Rheumatol Rep. 2011;13(2):123–31. Scholar
  51. 51.
    ter Haar NM, Oswald M, Jeyaratnam J, Anton J, Barron KS, Brogan PA, et al. Recommendations for the management of autoinflammatory diseases. Ann Rheum Dis. 2015;74(9):1636–44. Scholar
  52. 52.
    Sibley CH, Plass N, Snow J, Wiggs EA, Brewer CC, King KA, et al. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes. Arthritis Rheum. 2012;64(7):2375–86. Scholar
  53. 53.
    Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006;355(6):581–92. Scholar
  54. 54.
    Wittkowski H, Kuemmerle-Deschner JB, Austermann J, Holzinger D, Goldbach-Mansky R, Gramlich K, et al. MRP8 and MRP14, phagocyte-specific danger signals, are sensitive biomarkers of disease activity in cryopyrin-associated periodic syndromes. Ann Rheum Dis. 2011;70(12):2075–81. Scholar
  55. 55.
    Lepore L, Paloni G, Caorsi R, Alessio M, Rigante D, Ruperto N, et al. Follow-up and quality of life of patients with cryopyrin-associated periodic syndromes treated with Anakinra. J Pediatr. 2010;157(2):310–315.e1. Scholar
  56. 56.
    Kuemmerle-Deschner JB, Tyrrell PN, Koetter I, Wittkowski H, Bialkowski A, Tzaribachev N, et al. Efficacy and safety of anakinra therapy in pediatric and adult patients with the autoinflammatory Muckle-Wells syndrome. Arthritis Rheum. 2011;63(3):840–9. Scholar
  57. 57.
    Kuemmerle-Deschner JB, Wittkowski H, Tyrrell PN, Koetter I, Lohse P, Ummenhofer K, et al. Treatment of Muckle-Wells syndrome: analysis of two IL-1-blocking regimens. Arthritis Res Ther. 2013;15(3):R64. Scholar
  58. 58.
    Ross JB, Finlayson LA, Klotz PJ, Langley RG, Gaudet R, Thompson K, et al. Use of anakinra (Kineret) in the treatment of familial cold autoinflammatory syndrome with a 16-month follow-up. J Cutan Med Surg. 2008;12(1):8–16. Scholar
  59. 59.
    Hoffman HM, Throne ML, Amar NJ, Cartwright RC, Kivitz AJ, Soo Y, et al. Long-term efficacy and safety profile of rilonacept in the treatment of cryopryin-associated periodic syndromes: results of a 72-week open-label extension study. Clin Ther. 2012;34(10):2091–103. Scholar
  60. 60.
    Goldbach-Mansky R, Shroff SD, Wilson M, Snyder C, Plehn S, Barham B, et al. A pilot study to evaluate the safety and efficacy of the long-acting interleukin-1 inhibitor rilonacept (interleukin-1 Trap) in patients with familial cold autoinflammatory syndrome. Arthritis Rheum. 2008;58(8):2432–42. Scholar
  61. 61.
    Hoffman HM, Throne ML, Amar NJ, Sebai M, Kivitz AJ, Kavanaugh A, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008;58(8):2443–52. Scholar
  62. 62.
    Kone-Paut I, Lachmann HJ, Kuemmerle-Deschner JB, Hachulla E, Leslie KS, Mouy R, et al. Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study. Arthritis Res Ther. 2011;13(6):R202. Scholar
  63. 63.
    Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009;360(23):2416–25. Scholar
  64. 64.
    Kuemmerle-Deschner JB, Ramos E, Blank N, Roesler J, Felix SD, Jung T, et al. Canakinumab (ACZ885, a fully human IgG1 anti-IL-1beta mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Res Ther. 2011;13(1):R34. Scholar
  65. 65.
    Kuemmerle-Deschner JB, Hachulla E, Cartwright R, Hawkins PN, Tran TA, Bader-Meunier B, et al. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011;70(12):2095–102. Scholar
  66. 66.
    Sibley CH, Chioato A, Felix S, Colin L, Chakraborty A, Plass N, et al. A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease. Ann Rheum Dis. 2015;74(9):1714–9. Scholar
  67. 67.
    Yokota S, Imagawa T, Nishikomori R, Takada H, Abrams K, Lheritier K, et al. Long-term safety and efficacy of canakinumab in cryopyrin-associated periodic syndrome: results from an open-label, phase III pivotal study in Japanese patients. Clin Exp Rheumatol. 2017;35 Suppl 108(6):19–26.PubMedGoogle Scholar
  68. 68.
    Kuemmerle-Deschner JB, Hofer F, Endres T, Kortus-Goetze B, Blank N, Weissbarth-Riedel E, et al. Real-life effectiveness of canakinumab in cryopyrin-associated periodic syndrome. Rheumatology (Oxford, England). 2016;55(4):689–96. Scholar
  69. 69.
    Ter Haar N, Lachmann H, Ozen S, Woo P, Uziel Y, Modesto C, et al. Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review. Ann Rheum Dis. 2013;72(5):678–85. Scholar
  70. 70.
    Akula MK, Shi M, Jiang Z, Foster CE, Miao D, Li AS, et al. Control of the innate immune response by the mevalonate pathway. Nat Immunol. 2016;17(8):922–9. Scholar
  71. 71.
    Mandey SH, Kuijk LM, Frenkel J, Waterham HR. A role for geranylgeranylation in interleukin-1beta secretion. Arthritis Rheum. 2006;54(11):3690–5. Scholar
  72. 72.
    Drenth JP, Boom BW, Toonstra J, Van der Meer JW. Cutaneous manifestations and histologic findings in the hyperimmunoglobulinemia D syndrome. International Hyper IgD Study Group. Arch Dermatol. 1994;130(1):59–65.CrossRefPubMedGoogle Scholar
  73. 73.
    van der Meer JW, Vossen JM, Radl J, van Nieuwkoop JA, Meyer CJ, Lobatto S, et al. Hyperimmunoglobulinaemia D and periodic fever: a new syndrome. Lancet. 1984;1(8386):1087–90.CrossRefPubMedGoogle Scholar
  74. 74.
    Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, et al. Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet. 1999;22(2):175–7. Scholar
  75. 75.
    Cuisset L, Drenth JP, Simon A, Vincent MF, van der Velde Visser S, van der Meer JW, et al. Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome. Eur J Hum Genet EJHG. 2001;9(4):260–6. Scholar
  76. 76.
    Hoffmann GF, Charpentier C, Mayatepek E, Mancini J, Leichsenring M, Gibson KM, et al. Clinical and biochemical phenotype in 11 patients with mevalonic aciduria. Pediatrics. 1993;91(5):915–21.PubMedGoogle Scholar
  77. 77.
    van der Hilst JC, Bodar EJ, Barron KS, Frenkel J, Drenth JP, van der Meer JW, et al. Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Medicine (Baltimore). 2008;87(6):301–10. Scholar
  78. 78.
    Bader-Meunier B, Florkin B, Sibilia J, Acquaviva C, Hachulla E, Grateau G, et al. Mevalonate kinase deficiency: a survey of 50 patients. Pediatrics. 2011;128(1):e152–9. Scholar
  79. 79.
    Arostegui JI, Anton J, Calvo I, Robles A, Iglesias E, Lopez-Montesinos B, et al. Open-label, phase II study to assess the efficacy and safety of canakinumab treatment in active hyperimmunoglobulinemia D with periodic fever syndrome. Arthritis Rheumatol (Hoboken, NJ). 2017;69(8):1679–88. Scholar
  80. 80.
    Bodar EJ, Kuijk LM, Drenth JP, van der Meer JW, Simon A, Frenkel J. On-demand anakinra treatment is effective in mevalonate kinase deficiency. Ann Rheum Dis. 2011;70(12):2155–8. Scholar
  81. 81.
    Galeotti C, Meinzer U, Quartier P, Rossi-Semerano L, Bader-Meunier B, Pillet P, et al. Efficacy of interleukin-1-targeting drugs in mevalonate kinase deficiency. Rheumatology (Oxford, England). 2012;51(10):1855–9. Scholar
  82. 82.
    van der Burgh R, Ter Haar NM, Boes ML, Frenkel J. Mevalonate kinase deficiency, a metabolic autoinflammatory disease. Clin Immunol (Orlando, Fla). 2013;147(3):197–206. Scholar
  83. 83.
    Ter Haar NM, Jeyaratnam J, Lachmann HJ, Simon A, Brogan PA, Doglio M, et al. The phenotype and genotype of mevalonate kinase deficiency: a series of 114 cases from the Eurofever Registry. Arthritis Rheumatol (Hoboken, NJ). 2016;68(11):2795–805. Scholar
  84. 84.
    van der Hilst JC, Frenkel J. Hyperimmunoglobulin D syndrome in childhood. Curr Rheumatol Rep. 2010;12(2):101–7. Scholar
  85. 85.
    McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, et al. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell. 1999;97(1):133–44.CrossRefPubMedGoogle Scholar
  86. 86.
    Lachmann HJ, Papa R, Gerhold K, Obici L, Touitou I, Cantarini L, et al. The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry. Ann Rheum Dis. 2014;73(12):2160–7. Scholar
  87. 87.
    Toro JR, Aksentijevich I, Hull K, Dean J, Kastner DL. Tumor necrosis factor receptor-associated periodic syndrome: a novel syndrome with cutaneous manifestations. Arch Dermatol. 2000;136(12):1487–94.PubMedGoogle Scholar
  88. 88.
    Williamson LM, Hull D, Mehta R, Reeves WG, Robinson BH, Toghill PJ. Familial hibernian fever. Q J Med. 1982;51(204):469–80.PubMedGoogle Scholar
  89. 89.
    McDermott EM, Smillie DM, Powell RJ. Clinical spectrum of familial Hibernian fever: a 14-year follow-up study of the index case and extended family. Mayo Clin Proc. 1997;72(9):806–17. Scholar
  90. 90.
    Drewe E, McDermott EM, Powell PT, Isaacs JD, Powell RJ. Prospective study of anti-tumour necrosis factor receptor superfamily 1B fusion protein, and case study of anti-tumour necrosis factor receptor superfamily 1A fusion protein, in tumour necrosis factor receptor associated periodic syndrome (TRAPS): clinical and laboratory findings in a series of seven patients. Rheumatology (Oxford, England). 2003;42(2):235–9.CrossRefGoogle Scholar
  91. 91.
    Bulua AC, Mogul DB, Aksentijevich I, Singh H, He DY, Muenz LR, et al. Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome: a prospective, open-label, dose-escalation study. Arthritis Rheum. 2012;64(3):908–13. Scholar
  92. 92.
    Quillinan N, Mannion G, Mohammad A, Coughlan R, Dickie LJ, McDermott MF, et al. Failure of sustained response to etanercept and refractoriness to anakinra in patients with T50 M TNF-receptor-associated periodic syndrome. Ann Rheum Dis. 2011;70(9):1692–3. Scholar
  93. 93.
    Drewe E, Powell RJ, McDermott EM. Comment on: failure of anti-TNF therapy in TNF receptor 1-associated periodic syndrome (TRAPS). Rheumatology (Oxford, England). 2007;46(12):1865–6. Scholar
  94. 94.
    Jacobelli S, Andre M, Alexandra JF, Dode C, Papo T. Failure of anti-TNF therapy in TNF receptor 1-associated periodic syndrome (TRAPS). Rheumatology (Oxford, England). 2007;46(7):1211–2. Scholar
  95. 95.
    Gattorno M, Obici L, Cattalini M, Tormey V, Abrams K, Davis N, et al. Canakinumab treatment for patients with active recurrent or chronic TNF receptor-associated periodic syndrome (TRAPS): an open-label, phase II study. Ann Rheum Dis. 2017;76(1):173–8. Scholar
  96. 96.
    Brizi MG, Galeazzi M, Lucherini OM, Cantarini L, Cimaz R. Successful treatment of tumor necrosis factor receptor-associated periodic syndrome with canakinumab. Ann Intern Med. 2012;156(12):907–8. Scholar
  97. 97.
    Gattorno M, Pelagatti MA, Meini A, Obici L, Barcellona R, Federici S, et al. Persistent efficacy of anakinra in patients with tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum. 2008;58(5):1516–20. Scholar
  98. 98.
    Greco E, Aita A, Galozzi P, Gava A, Sfriso P, Negm OH, et al. The novel S59P mutation in the TNFRSF1A gene identified in an adult onset TNF receptor associated periodic syndrome (TRAPS) constitutively activates NF-kappaB pathway. Arthritis Res Ther. 2015;17:93. Scholar
  99. 99.
    Simon A, Bodar EJ, van der Hilst JC, van der Meer JW, Fiselier TJ, Cuppen MP, et al. Beneficial response to interleukin 1 receptor antagonist in traps. Am J Med. 2004;117(3):208–10.CrossRefPubMedGoogle Scholar
  100. 100.
    Akasbi N, Soyfoo MS. Successful treatment of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) with tocilizumab: a case report. Eur J Rheumatol. 2015;2(1):35–6. Scholar
  101. 101.
    Vaitla PM, Radford PM, Tighe PJ, Powell RJ, McDermott EM, Todd I, et al. Role of interleukin-6 in a patient with tumor necrosis factor receptor-associated periodic syndrome: assessment of outcomes following treatment with the anti-interleukin-6 receptor monoclonal antibody tocilizumab. Arthritis Rheum. 2011;63(4):1151–5. Scholar
  102. 102.
    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.CrossRefPubMedGoogle Scholar
  103. 103.
    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(6):2022–7. Scholar
  104. 104.
    Caorsi R, Marotto D, Insalaco A, Marzano A, Frenkel J, Martini A, et al. The phenotypic variability of PAPA syndrome: evidence from the Eurofever Registry. Pediatr Rheumatol Online J. 2015;13(Suppl 1):O8-O. Scholar
  105. 105.
    Dierselhuis MP, Frenkel J, Wulffraat NM, Boelens JJ. Anakinra for flares of pyogenic arthritis in PAPA syndrome. Rheumatology (Oxford, England). 2005;44(3):406–8. Scholar
  106. 106.
    Caorsi R, Picco P, Buoncompagni A, Martini A, Gattorno M. Osteolytic lesion in PAPA syndrome responding to anti-interleukin 1 treatment. J Dermatol. 2014;41(11):2333–4. Scholar
  107. 107.
    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(5):1199–201. Scholar
  108. 108.
    Geusau A, Mothes-Luksch N, Nahavandi H, Pickl WF, Wise CA, Pourpak Z, et al. Identification of a homozygous PSTPIP1 mutation in a patient with a PAPA-like syndrome responding to canakinumab treatment. JAMA Dermatol. 2013;149(2):209–15. Scholar
  109. 109.
    Omenetti A, Carta S, Caorsi R, Finetti M, Marotto D, Lattanzi B, et al. Disease activity accounts for long-term efficacy of IL-1 blockers in pyogenic sterile arthritis pyoderma gangrenosum and severe acne syndrome. Rheumatology (Oxford, England). 2016;55(7):1325–35. Scholar
  110. 110.
    Masters SL, Lagou V, Jeru I, Baker PJ, Van Eyck L, Parry DA, et al. Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation. Sci Transl Med. 2016;8(332):332ra45. Scholar
  111. 111.
    Moghaddas F, Llamas R, De Nardo D, Martinez-Banaclocha H, Martinez-Garcia JJ, Mesa-Del-Castillo P, et al. A novel pyrin-associated autoinflammation with neutrophilic dermatosis mutation further defines 14-3-3 binding of pyrin and distinction to familial Mediterranean fever. Ann Rheum Dis. 2017;76(12):2085–94. Scholar
  112. 112.
    Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, et al. CARD15 mutations in Blau syndrome. Nat Genet. 2001;29(1):19–20. Scholar
  113. 113.
    Chamaillard M, Philpott D, Girardin SE, Zouali H, Lesage S, Chareyre F, et al. Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases. Proc Natl Acad Sci USA. 2003;100(6):3455–60. Scholar
  114. 114.
    Shwin KW, Lee CR, Goldbach-Mansky R. Dermatologic manifestations of monogenic autoinflammatory diseases. Dermatol Clin. 2017;35(1):21–38. Scholar
  115. 115.
    Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature. 2001;411(6837):603–6. Scholar
  116. 116.
    Kanazawa N, Okafuji I, Kambe N, Nishikomori R, Nakata-Hizume M, Nagai S, et al. Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome. Blood. 2005;105(3):1195–7. Scholar
  117. 117.
    Nagakura T, Wakiguchi H, Kubota T, Yamatou T, Yamasaki Y, Nonaka Y, et al. Tumor necrosis factor inhibitors provide longterm clinical benefits in pediatric and young adult patients with Blau syndrome. J Rheumatol. 2017;44(4):536–8. Scholar
  118. 118.
    Milman N, Andersen CB, Hansen A, van Overeem Hansen T, Nielsen FC, Fledelius H, et al. Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation. APMIS acta pathologica, microbiologica, et immunologica Scandinavica. 2006;114(12):912–9. Scholar
  119. 119.
    Caracseghi F, Izquierdo-Blasco J, Sanchez-Montanez A, Melendo-Perez S, Roig-Quilis M, Modesto C. Etanercept-induced myelopathy in a pediatric case of Blau syndrome. Case Rep Rheumatol. 2011;2011:5. Scholar
  120. 120.
    Arostegui JI, Arnal C, Merino R, Modesto C, Antonia Carballo M, Moreno P, et al. NOD2 gene-associated pediatric granulomatous arthritis: clinical diversity, novel and recurrent mutations, and evidence of clinical improvement with interleukin-1 blockade in a Spanish cohort. Arthritis Rheum. 2007;56(11):3805–13. Scholar
  121. 121.
    Yi Yong C. Blau syndrome treated with sequential biologics. Rheumatol Adv Pract. 2018;2(s1):i43.Google Scholar
  122. 122.
    Martin TM, Zhang Z, Kurz P, Rose CD, Chen H, Lu H, et al. The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity. Arthritis Rheum. 2009;60(2):611–8. Scholar
  123. 123.
    Simonini G, Xu Z, Caputo R, De Libero C, Pagnini I, Pascual V, et al. Clinical and transcriptional response to the long-acting interleukin-1 blocker canakinumab in Blau syndrome-related uveitis. Arthritis Rheum. 2013;65(2):513–8. Scholar
  124. 124.
    Lu L, Shen M, Jiang D, Li Y, Zheng X, Li Y, et al. Blau syndrome with good responses to tocilizumab: a case report and focused literature review. Semin Arthritis Rheum. 2018;47(5):727–31. Scholar
  125. 125.
    Rose CD, Pans S, Casteels I, Anton J, Bader-Meunier B, Brissaud P, et al. Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes. Rheumatology (Oxford, England). 2015;54(6):1008–16. Scholar
  126. 126.
    Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A, et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009;360(23):2426–37. Scholar
  127. 127.
    Reddy S, Jia S, Geoffrey R, Lorier R, Suchi M, Broeckel U, et al. An autoinflammatory disease due to homozygous deletion of the IL1RN locus. N Engl J Med. 2009;360(23):2438–44. Scholar
  128. 128.
    Naik HB, Cowen EW. Autoinflammatory pustular neutrophilic diseases. Dermatol Clin. 2013;31(3):405–25. Scholar
  129. 129.
    Garg M, de Jesus AA, Chapelle D, Dancey P, Herzog R, Rivas-Chacon R, et al. Rilonacept maintains long-term inflammatory remission in patients with deficiency of the IL-1 receptor antagonist. JCI Insight. 2017. Scholar
  130. 130.
    Schnellbacher C, Ciocca G, Menendez R, Aksentijevich I, Goldbach-Mansky R, Duarte AM, et al. Deficiency of interleukin-1 receptor antagonist responsive to anakinra. Pediatr Dermatol. 2013;30(6):758–60. Scholar
  131. 131.
    Ulusoy E, Karaca NE, El-Shanti H, Kilicoglu E, Aksu G, Kutukculer N. Interleukin-1 receptor antagonist deficiency with a novel mutation; late onset and successful treatment with canakinumab: a case report. J Med Case Rep. 2015;9:145. Scholar
  132. 132.
    Tortola L, Rosenwald E, Abel B, Blumberg H, Schafer M, Coyle AJ, et al. Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk. J Clin Investig. 2012;122(11):3965–76. Scholar
  133. 133.
    Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY, Fraitag S, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365(7):620–8. Scholar
  134. 134.
    Kumar S, McDonnell PC, Lehr R, Tierney L, Tzimas MN, Griswold DE, et al. Identification and initial characterization of four novel members of the interleukin-1 family. J Biol Chem. 2000;275(14):10308–14.CrossRefPubMedGoogle Scholar
  135. 135.
    Torrelo A, Patel S, Colmenero I, Gurbindo D, Lendinez F, Hernandez A, et al. Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. J Am Acad Dermatol. 2010;62(3):489–95. Scholar
  136. 136.
    Liu Y, Ramot Y, Torrelo A, Paller AS, Si N, Babay S, et al. Mutations in proteasome subunit beta type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum. 2012;64(3):895–907. Scholar
  137. 137.
    Brehm A, Liu Y, Sheikh A, Marrero B, Omoyinmi E, Zhou Q, et al. Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. J Clin Investig. 2015;125(11):4196–211. Scholar
  138. 138.
    Kitamura A, Maekawa Y, Uehara H, Izumi K, Kawachi I, Nishizawa M, et al. A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans. J Clin Investig. 2011;121(10):4150–60. Scholar
  139. 139.
    Montealegre G, Reinhardt A, Brogan P, Berkun Y, Zlotogorski A, Brown D, et al. Preliminary response to Janus kinase inhibition with baricitinib in chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE). Pediatric rheumatol Online J. 2015;13(Suppl 1):O31-O. Scholar
  140. 140.
    Jeremiah N, Neven B, Gentili M, Callebaut I, Maschalidi S, Stolzenberg MC, et al. Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J Clin Investig. 2014;124(12):5516–20. Scholar
  141. 141.
    Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Sanchez GAM, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014;371(6):507–18. Scholar
  142. 142.
    Sanchez GAM, Reinhardt A, Ramsey S, Wittkowski H, Hashkes PJ, Berkun Y, et al. JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Investig. 2018;128(7):3041–52. Scholar
  143. 143.
    Konig N, Fiehn C, Wolf C, Schuster M, Cura Costa E, Tungler V, et al. Familial chilblain lupus due to a gain-of-function mutation in STING. Ann Rheum Dis. 2017;76(2):468–72. Scholar
  144. 144.
    Fremond ML, Rodero MP, Jeremiah N, Belot A, Jeziorski E, Duffy D, et al. Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in 3 children. J Allergy Clin Immunol. 2016;138(6):1752–5. Scholar
  145. 145.
    Akiyama M, Takeichi T, McGrath JA, Sugiura K. Autoinflammatory keratinization diseases: an emerging concept encompassing various inflammatory keratinization disorders of the skin. J Dermatol Sci. 2018;90(2):105–11. Scholar
  146. 146.
    Akiyama M, Takeichi T, McGrath JA, Sugiura K. Autoinflammatory keratinization diseases. J Allergy Clin Immunol. 2017;140(6):1545–7. Scholar
  147. 147.
    De Vita V, McGonagle D. Hidradenitis suppurativa as an autoinflammatory keratinization disease. J Allergy Clin Immunol. 2018;141(5):1953. Scholar
  148. 148.
    Takeichi T, Akiyama M. Familial or sporadic porokeratosis as an autoinflammatory keratinization disease. J Dermatol. 2018. Scholar
  149. 149.
    von Laffert M, Helmbold P, Wohlrab J, Fiedler E, Stadie V, Marsch WC. Hidradenitis suppurativa (acne inversa): early inflammatory events at terminal follicles and at interfollicular epidermis. Exp Dermatol. 2010;19(6):533–7. Scholar
  150. 150.
    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. Scholar
  151. 151.
    Schlapbach C, Hanni T, Yawalkar N, Hunger RE. Expression of the IL-23/Th17 pathway in lesions of hidradenitis suppurativa. J Am Acad Dermatol. 2011;65(4):790–8. Scholar
  152. 152.
    Kelly G, Hughes R, McGarry T, van den Born M, Adamzik K, Fitzgerald R, et al. Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa. Br J Dermatol. 2015;173(6):1431–9. Scholar
  153. 153.
    van der Zee HH, de Ruiter L, van den Broecke DG, Dik WA, Laman JD, Prens EP. Elevated levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-alpha and IL-1beta. Br J Dermatol. 2011;164(6):1292–8. Scholar
  154. 154.
    Ring HC, Emtestam L. The microbiology of hidradenitis suppurativa. Dermatol Clin. 2016;34(1):29–35. Scholar
  155. 155.
    Jemec GB. Clinical practice. Hidradenitis suppurativa. N Engl J Med. 2012;366(2):158–64. Scholar
  156. 156.
    Adams DR, Yankura JA, Fogelberg AC, Anderson BE. Treatment of hidradenitis suppurativa with etanercept injection. Arch Dermatol. 2010;146(5):501–4. Scholar
  157. 157.
    Blok JL, Li K, Brodmerkel C, Horvatovich P, Jonkman MF, Horvath B. Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum. Br J Dermatol. 2016;174(4):839–46. Scholar
  158. 158.
    Zarchi K, Dufour DN, Jemec GB. Successful treatment of severe hidradenitis suppurativa with anakinra. JAMA Dermatol. 2013;149(10):1192–4. Scholar
  159. 159.
    van der Zee HH, Prens EP. Failure of anti-interleukin-1 therapy in severe hidradenitis suppurativa: a case report. Dermatology (Basel, Switzerland). 2013;226(2):97–100. Scholar
  160. 160.
    Menis D, Maronas-Jimenez L, Delgado-Marquez AM, Postigo-Llorente C, Vanaclocha-Sebastian F. Two cases of severe hidradenitis suppurativa with failure of anakinra therapy. Br J Dermatol. 2015;172(3):810–1. Scholar
  161. 161.
    Tzanetakou V, Kanni T, Giatrakou S, Katoulis A, Papadavid E, Netea MG, et al. Safety and efficacy of anakinra in severe hidradenitis suppurativa: a randomized clinical trial. JAMA Dermatol. 2016;152(1):52–9. Scholar
  162. 162.
    Navarini AA, Burden AD, Capon F, Mrowietz U, Puig L, Koks S, et al. European consensus statement on phenotypes of pustular psoriasis. J Eur Acad Dermatol Venereol JEADV. 2017;31(11):1792–9. Scholar
  163. 163.
    Umezawa Y, Ozawa A, Kawasima T, Shimizu H, Terui T, Tagami H, et al. Therapeutic guidelines for the treatment of generalized pustular psoriasis (GPP) based on a proposed classification of disease severity. Arch Dermatol Res. 2003;295(Suppl 1):S43–54. Scholar
  164. 164.
    Jordan CT, Cao L, Roberson ED, Pierson KC, Yang CF, Joyce CE, et al. PSORS2 is due to mutations in CARD14. Am J Hum Genet. 2012;90(5):784–95. Scholar
  165. 165.
    Sugiura K, Muto M, Akiyama M. CARD14 c.526G > C (p.Asp176His) is a significant risk factor for generalized pustular psoriasis with psoriasis vulgaris in the Japanese cohort. J Investig Dermatol. 2014;134(6):1755–7. Scholar
  166. 166.
    Jordan CT, Cao L, Roberson ED, Duan S, Helms CA, Nair RP, et al. Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis. Am J Hum Genet. 2012;90(5):796–808. Scholar
  167. 167.
    Sugiura K, Takemoto A, Yamaguchi M, Takahashi H, Shoda Y, Mitsuma T, et al. The majority of generalized pustular psoriasis without psoriasis vulgaris is caused by deficiency of interleukin-36 receptor antagonist. J Invest Dermatol. 2013;133(11):2514–21. Scholar
  168. 168.
    Robinson A, Van Voorhees AS, Hsu S, Korman NJ, Lebwohl MG, Bebo BF Jr, et al. Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2012;67(2):279–88. Scholar
  169. 169.
    Mansouri B, Richards L, Menter A. Treatment of two patients with generalized pustular psoriasis with the interleukin-1beta inhibitor gevokizumab. Br J Dermatol. 2015;173(1):239–41. Scholar
  170. 170.
    Skendros P, Papagoras C, Lefaki I, Giatromanolaki A, Kotsianidis I, Speletas M, et al. Successful response in a case of severe pustular psoriasis after interleukin-1beta inhibition. Br J Dermatol. 2017;176(1):212–5. Scholar
  171. 171.
    Viguier M, Guigue P, Pages C, Smahi A, Bachelez H. Successful treatment of generalized pustular psoriasis with the interleukin-1-receptor antagonist anakinra: lack of correlation with IL1RN mutations. Ann Intern Med. 2010;153(1):66–7. Scholar
  172. 172.
    Huffmeier U, Watzold M, Mohr J, Schon MP, Mossner R. Successful therapy with anakinra in a patient with generalized pustular psoriasis carrying IL36RN mutations. Br J Dermatol. 2014;170(1):202–4. Scholar
  173. 173.
    Saeki H, Nakagawa H, Nakajo K, Ishii T, Morisaki Y, Aoki T, et al. Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: results from a 52-week, open-label, phase 3 study (UNCOVER-J). J Dermatol. 2017;44(4):355–62. Scholar
  174. 174.
    Imafuku S, Honma M, Okubo Y, Komine M, Ohtsuki M, Morita A, et al. Efficacy and safety of secukinumab in patients with generalized pustular psoriasis: a 52-week analysis from phase III open-label multicenter Japanese study. J Dermatol. 2016;43(9):1011–7. Scholar
  175. 175.
    Yamasaki K, Nakagawa H, Kubo Y, Ootaki K. Efficacy and safety of brodalumab in patients with generalized pustular psoriasis and psoriatic erythroderma: results from a 52-week, open-label study. Br J Dermatol. 2017;176(3):741–51. Scholar
  176. 176.
    Hoegler KM, John AM, Handler MZ, Schwartz RA. Generalized pustular psoriasis: a review and update on treatment. J Eur Acad Dermatol Venereol JEADV. 2018;32(10):1645–51. Scholar
  177. 177.
    Misiak-Galazka M, Wolska H, Rudnicka L. What do we know about palmoplantar pustulosis? J Eur Acad Dermatol Venereol JEADV. 2017;31(1):38–44. Scholar
  178. 178.
    Burden AD, Kemmett D. The spectrum of nail involvement in palmoplantar pustulosis. Br J Dermatol. 1996;134(6):1079–82.CrossRefPubMedGoogle Scholar
  179. 179.
    Eriksson MO, Hagforsen E, Lundin IP, Michaelsson G. Palmoplantar pustulosis: a clinical and immunohistological study. Br J Dermatol. 1998;138(3):390–8.CrossRefPubMedGoogle Scholar
  180. 180.
    Mossner R, Frambach Y, Wilsmann-Theis D, Lohr S, Jacobi A, Weyergraf A, et al. Palmoplantar pustular psoriasis is associated with missense variants in CARD14, but not with loss-of-function mutations in IL36RN in European patients. J Invest Dermatol. 2015;135(10):2538–41. Scholar
  181. 181.
    Sevrain M, Richard MA, Barnetche T, Rouzaud M, Villani AP, Paul C, et al. Treatment for palmoplantar pustular psoriasis: systematic literature review, evidence-based recommendations and expert opinion. J Eur Acad Dermatol Venereol JEADV. 2014;28(Suppl 5):13–6. Scholar
  182. 182.
    Tauber M, Viguier M, Alimova E, Petit A, Liote F, Smahi A, et al. Partial clinical response to anakinra in severe palmoplantar pustular psoriasis. Br J Dermatol. 2014;171(3):646–9. Scholar
  183. 183.
    Younis S, Rimar D, Slobodin G, Rosner I. Tumor necrosis factor-associated palmoplantar pustular psoriasis treated with interleukin 6 blocker. J Rheumatol. 2012;39(10):2055–6. Scholar
  184. 184.
    Floristan U, Feltes R, Ramirez P, Alonso ML, De Lucas R. Recalcitrant palmoplantar pustular psoriasis treated with etanercept. Pediatr Dermatol. 2011;28(3):349–50. Scholar
  185. 185.
    Bertelsen T, Kragballe K, Johansen C, Iversen L. Efficacy of ustekinumab in palmoplantar pustulosis and palmoplantar pustular psoriasis. Int J Dermatol. 2014;53(10):e464–6. Scholar
  186. 186.
    Morales-Munera C, Vilarrasa E, Puig L. Efficacy of ustekinumab in refractory palmoplantar pustular psoriasis. Br J Dermatol. 2013;168(4):820–4. Scholar
  187. 187.
    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(6):813–21. Scholar
  188. 188.
    Okuno H, Watanuki M, Kuwahara Y, Sekiguchi A, Mori Y, Hitachi S, et al. Clinical features and radiological findings of 67 patients with SAPHO syndrome. Mod Rheumatol. 2018;28(4):703–8. Scholar
  189. 189.
    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, England). 2010;49(7):1416–8. Scholar
  190. 190.
    Daoussis D, Konstantopoulou G, Kraniotis P, Sakkas L, Liossis SN. Biologics in SAPHO syndrome: a systematic review. Semin Arthritis Rheum. 2018. Scholar
  191. 191.
    Jung J, Molinger M, Kohn D, Schreiber M, Pfreundschuh M, Assmann G. Intra-articular glucocorticosteroid injection into sternocostoclavicular joints in patients with SAPHO syndrome. Semin Arthritis Rheum. 2012;42(3):266–70. Scholar
  192. 192.
    Burgemeister LT, Baeten DL, Tas SW. Biologics for rare inflammatory diseases: TNF blockade in the SA PHO syndrome. Neth J Med. 2012;70(10):444–9.PubMedGoogle Scholar
  193. 193.
    Wendling D, Prati C, Aubin F. Anakinra treatment of SAPHO syndrome: short-term results of an open study. Ann Rheum Dis. 2012;71(6):1098–100. Scholar
  194. 194.
    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(3):199–205.CrossRefPubMedGoogle Scholar
  195. 195.
    Wendling D, Aubin F, Verhoeven F, Prati C. IL-23/Th17 targeted therapies in SAPHO syndrome. A case series. Jt Bone Spine Revue Du Rhum. 2017;84(6):733–5. Scholar
  196. 196.
    Cornillier H, Kervarrec T, Tabareau-Delalande F, Mammou S, Jonville Bera AP, Machet L. Interstitial granulomatous dermatitis occurring in a patient with SAPHO syndrome one month after starting leflunomide, and subsequently disappearing with ustekinumab. Eur J Dermatol EJD. 2016;26(6):614–5. Scholar
  197. 197.
    Calderon-Castrat X, Bancalari-Diaz D, Roman-Curto C, Romo-Melgar A, Amoros-Cerdan D, Alcaraz-Mas LA, et al. PSTPIP1 gene mutation in a pyoderma gangrenosum, acne and suppurative hidradenitis (PASH) syndrome. Br J Dermatol. 2016;175(1):194–8. Scholar
  198. 198.
    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. Scholar
  199. 199.
    Duchatelet S, Miskinyte S, Join-Lambert O, Ungeheuer MN, Frances C, Nassif A, et al. First nicastrin mutation in PASH (pyoderma gangrenosum, acne and suppurative hidradenitis) syndrome. Br J Dermatol. 2015;173(2):610–2. Scholar
  200. 200.
    Marzano AV, Damiani G, Ceccherini I, Berti E, Gattorno M, Cugno M. Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis). Br J Dermatol. 2017;176(6):1588–98. Scholar
  201. 201.
    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. Scholar
  202. 202.
    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. Scholar
  203. 203.
    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 JEADV. 2015;29(11):2243–7. Scholar
  204. 204.
    De Wet J, Jordaan HF, Kannenberg SM, Tod B, Glanzmann B, Visser WI. Pyoderma gangrenosum, acne, and suppurative hidradenitis syndrome in end-stage renal disease successfully treated with adalimumab. Dermatol Online J. 2017;23(12).Google Scholar
  205. 205.
    Fattore D, Pistone G, Bongiorno MR. Pyoderma gangrenosum, acne, hidradenitis suppurativa syndrome associated with type 1 diabetes mellitus treated with adalimumab. G Ital Dermatol Venereol. 2019;154(2):218–20. Scholar
  206. 206.
    Murphy B, Morrison G, Podmore P. Successful use of adalimumab to treat pyoderma gangrenosum, acne and suppurative hidradenitis (PASH syndrome) following colectomy in ulcerative colitis. Int J Colorect Dis. 2015;30(8):1139–40. Scholar
  207. 207.
    Saint-Georges V, Peternel S, Kastelan M, Brajac I. Tumor necrosis factor antagonists in the treatment of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) syndrome. Acta dermatovenerol Croat ADC. 2018;26(2):173–8.PubMedGoogle Scholar
  208. 208.
    Sarica-Kucukoglu R, Akdag-Kose A, Kayabal IM, Yazganoglu KD, Disci R, Erzengin D, et al. Vascular involvement in Behcet’s disease: a retrospective analysis of 2319 cases. Int J Dermatol. 2006;45(8):919–21. Scholar
  209. 209.
    Nelson CA, Stephen S, Ashchyan HJ, James WD, Micheletti RG, Rosenbach M. Neutrophilic dermatoses: pathogenesis, Sweet syndrome, neutrophilic eccrine hidradenitis, and Behcet disease. J Am Acad Dermatol. 2018;79(6):987–1006. Scholar
  210. 210.
    Touitou I, Magne X, Molinari N, Navarro A, Quellec AL, Picco P, et al. MEFV mutations in Behcet’s disease. Hum Mutat. 2000;16(3):271–2.;2-a.CrossRefPubMedGoogle Scholar
  211. 211.
    Wu Z, Zhang S, Li J, Chen S, Li P, Sun F, et al. Association between MEFV mutations M694 V and M680I and Behcet’s disease: a meta-analysis. PLoS One. 2015;10(7):e0132704. Scholar
  212. 212.
    Adeeb F, Stack AG, Fraser AD. Knitting the threads of silk through time: behcet’s disease-past, present, and future. Int J Rheumatol. 2017;2017:2160610. Scholar
  213. 213.
    Lehner T, Lavery E, Smith R, van der Zee R, Mizushima Y, Shinnick T. Association between the 65-kilodalton heat shock protein, Streptococcus sanguis, and the corresponding antibodies in Behcet’s syndrome. Infect Immun. 1991;59(4):1434–41.PubMedPubMedCentralGoogle Scholar
  214. 214.
    Kaneko F, Oyama N, Yanagihori H, Isogai E, Yokota K, Oguma K. The role of streptococcal hypersensitivity in the pathogenesis of Behcet’s disease. Eur J Dermatol EJD. 2008;18(5):489–98. Scholar
  215. 215.
    Alpsoy E. Behcet’s disease: a comprehensive review with a focus on epidemiology, etiology and clinical features, and management of mucocutaneous lesions. J Dermatol. 2016;43(6):620–32. Scholar
  216. 216.
    Zhou Q, Wang H, Schwartz DM, Stoffels M, Park YH, Zhang Y, et al. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease. Nat Genet. 2016;48(1):67–73. Scholar
  217. 217.
    Leccese P, Ozguler Y, Christensen R, Esatoglu SN, Bang D, Bodaghi B, et al. Management of skin, mucosa and joint involvement of Behcet’s syndrome: a systematic review for update of the EULAR recommendations for the management of Behcet’s syndrome. Semin Arthritis Rheum. 2018. Scholar
  218. 218.
    Hatemi G, Christensen R, Bang D, Bodaghi B, Celik AF, Fortune F, et al. 2018 update of the EULAR recommendations for the management of Behcet’s syndrome. Ann Rheum Dis. 2018;77(6):808–18. Scholar
  219. 219.
    Cantarini L, Vitale A, Scalini P, Dinarello CA, Rigante D, Franceschini R, et al. Anakinra treatment in drug-resistant Behcet’s disease: a case series. Clin Rheumatol. 2015;34(7):1293–301. Scholar
  220. 220.
    Grayson PC, Yazici Y, Merideth M, Sen HN, Davis M, Novakovich E, et al. Treatment of mucocutaneous manifestations in Behcet’s disease with anakinra: a pilot open-label study. Arthritis Res Ther. 2017;19(1):69. Scholar
  221. 221.
    Vitale A, Rigante D, Caso F, Brizi MG, Galeazzi M, Costa L, et al. Inhibition of interleukin-1 by canakinumab as a successful mono-drug strategy for the treatment of refractory Behcet’s disease: a case series. Dermatology (Basel, Switzerland). 2014;228(3):211–4. Scholar
  222. 222.
    Emmi G, Talarico R, Lopalco G, Cimaz R, Cantini F, Viapiana O, et al. Efficacy and safety profile of anti-interleukin-1 treatment in Behcet’s disease: a multicenter retrospective study. Clin Rheumatol. 2016;35(5):1281–6. Scholar
  223. 223.
    Hirano T, Ohguro N, Hohki S, Hagihara K, Shima Y, Narazaki M, et al. A case of Behcet’s disease treated with a humanized anti-interleukin-6 receptor antibody, tocilizumab. Mod Rheumatol. 2012;22(2):298–302. Scholar
  224. 224.
    Caso F, Iaccarino L, Bettio S, Ometto F, Costa L, Punzi L, et al. Refractory pemphigus foliaceus and Behcet’s disease successfully treated with tocilizumab. Immunol Res. 2013;56(2–3):390–7. Scholar
  225. 225.
    Shapiro LS, Farrell J, Borhani Haghighi A. Tocilizumab treatment for neuro-Behcet’s disease, the first report. Clin Neurol Neurosurg. 2012;114(3):297–8. Scholar
  226. 226.
    Urbaniak P, Hasler P, Kretzschmar S. Refractory neuro-Behcet treated by tocilizumab: a case report. Clin Exp Rheumatol. 2012;30(3 Suppl 72):S73–5.PubMedGoogle Scholar
  227. 227.
    Diamantopoulos AP, Hatemi G. Lack of efficacy of tocilizumab in mucocutaneous Behcet’s syndrome: report of two cases. Rheumatology (Oxford, England). 2013;52(10):1923–4. Scholar
  228. 228.
    Nigrovic PA, Raychaudhuri S, Thompson SD. Review: genetics and the classification of arthritis in adults and children. Arthritis Rheumatol (Hoboken, NJ). 2018;70(1):7–17. Scholar
  229. 229.
    Martini A. It is time to rethink juvenile idiopathic arthritis classification and nomenclature. Ann Rheum Dis. 2012;71(9):1437–9. Scholar
  230. 230.
    Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005;201(9):1479–86. Scholar
  231. 231.
    Bielak M, Husmann E, Weyandt N, Haas JP, Hugle B, Horneff G, et al. IL-6 blockade in systemic juvenile idiopathic arthritis—achievement of inactive disease and remission (data from the German AID-registry). Pediatr Rheumatol Online J. 2018;16(1):22. Scholar
  232. 232.
    Yokota S, Imagawa T, Mori M, Miyamae T, Aihara Y, Takei S, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. 2008;371(9617):998–1006. Scholar
  233. 233.
    Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2396–406. Scholar
  234. 234.
    De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2385–95. Scholar
  235. 235.
    Lovell DJ, Giannini EH, Reiff AO, Kimura Y, Li S, Hashkes PJ, et al. Long-term safety and efficacy of rilonacept in patients with systemic juvenile idiopathic arthritis. Arthritis Rheum. 2013;65(9):2486–96. Scholar
  236. 236.
    Quartier P, Allantaz F, Cimaz R, Pillet P, Messiaen C, Bardin C, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2011;70(5):747–54. Scholar
  237. 237.
    Ilowite NT, Prather K, Lokhnygina Y, Schanberg LE, Elder M, Milojevic D, et al. Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis. Arthritis Rheumatol (Hoboken, NJ). 2014;66(9):2570–9. Scholar
  238. 238.
    Tarp S, Amarilyo G, Foeldvari I, Christensen R, Woo JM, Cohen N, et al. Efficacy and safety of biological agents for systemic juvenile idiopathic arthritis: a systematic review and meta-analysis of randomized trials. Rheumatology (Oxford, England). 2016;55(4):669–79. Scholar
  239. 239.
    Toplak N, Blazina S, Avcin T. The role of IL-1 inhibition in systemic juvenile idiopathic arthritis: current status and future perspectives. Drug Des Dev Ther. 2018;12:1633–43. Scholar
  240. 240.
    Castaneda S, Blanco R, Gonzalez-Gay MA. Adult-onset Still’s disease: advances in the treatment. Best Pract Res Clin Rheumatol. 2016;30(2):222–38. Scholar
  241. 241.
    Gerfaud-Valentin M, Maucort-Boulch D, Hot A, Iwaz J, Ninet J, Durieu I, et al. Adult-onset still disease: manifestations, treatment, outcome, and prognostic factors in 57 patients. Medicine (Baltimore). 2014;93(2):91–9. Scholar
  242. 242.
    Fautrel B, Sibilia J, Mariette X, Combe B. Tumour necrosis factor alpha blocking agents in refractory adult Still’s disease: an observational study of 20 cases. Ann Rheum Dis. 2005;64(2):262–6. Scholar
  243. 243.
    Kalliolias GD, Georgiou PE, Antonopoulos IA, Andonopoulos AP, Liossis S-NC. Anakinra treatment in patients with adult-onset Still’s disease is fast, effective, safe and steroid sparing: experience from an uncontrolled trial. Anna Rheum Dis. 2007;66(6):842–3. Scholar
  244. 244.
    Lequerre T, Quartier P, Rosellini D, Alaoui F, De Bandt M, Mejjad O, et al. Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France. Ann Rheum Dis. 2008;67(3):302–8. Scholar
  245. 245.
    Laskari K, Tzioufas AG, Moutsopoulos HM. Efficacy and long-term follow-up of IL-1R inhibitor anakinra in adults with Still’s disease: a case-series study. Arthritis Res Ther. 2011;13(3):R91. Scholar
  246. 246.
    Nordstrom D, Knight A, Luukkainen R, van Vollenhoven R, Rantalaiho V, Kajalainen A, et al. Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset Still’s disease. An open, randomized, multicenter study. J Rheumatol. 2012;39(10):2008–11. Scholar
  247. 247.
    Ortiz-Sanjuan F, Blanco R, Riancho-Zarrabeitia L, Castaneda S, Olive A, Riveros A, et al. Efficacy of anakinra in refractory adult-onset Still’s disease: multicenter study of 41 patients and literature review. Medicine (Baltimore). 2015;94(39):e1554. Scholar
  248. 248.
    Kontzias A, Efthimiou P. The use of canakinumab, a novel IL-1beta long-acting inhibitor, in refractory adult-onset Still’s disease. Semin Arthritis Rheum. 2012;42(2):201–5. Scholar
  249. 249.
    Lo Gullo A, Caruso A, Pipitone N, Macchioni P, Pazzola G, Salvarani C. Canakinumab in a case of adult onset still’s disease: efficacy only on systemic manifestations. Jt Bone Spin Revue Du Rhum. 2014;81(4):376–7. Scholar
  250. 250.
    Kaneko Y, Kameda H, Ikeda K, Ishii T, Murakami K, Takamatsu H, et al. Tocilizumab in patients with adult-onset still’s disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial. Ann Rheum Dis. 2018;77(12):1720–9. Scholar
  251. 251.
    Simon A, Asli B, Braun-Falco M, De Koning H, Fermand JP, Grattan C, et al. Schnitzler’s syndrome: diagnosis, treatment, and follow-up. Allergy. 2013;68(5):562–8. Scholar
  252. 252.
    Loock J, Lamprecht P, Timmann C, Mrowietz U, Csernok E, Gross WL. Genetic predisposition (NLRP3 V198 M mutation) for IL-1-mediated inflammation in a patient with Schnitzler syndrome. J Allergy Clin Immunol. 2010;125(2):500–2. Scholar
  253. 253.
    Rowczenio DM, Trojer H, Russell T, Baginska A, Lane T, Stewart NM, et al. Clinical characteristics in subjects with NLRP3 V198 M diagnosed at a single UK center and a review of the literature. Arthritis Res Ther. 2013;15(1):R30. Scholar
  254. 254.
    Rowczenio DM, Pathak S, Arostegui JI, Mensa-Vilaro A, Omoyinmi E, Brogan P, et al. Molecular genetic investigation, clinical features, and response to treatment in 21 patients with Schnitzler syndrome. Blood. 2018;131(9):974–81. Scholar
  255. 255.
    Pizzirani C, Falzoni S, Govoni M, La Corte R, Donadei S, Di Virgilio F, et al. Dysfunctional inflammasome in Schnitzler’s syndrome. Rheumatology (Oxford, England). 2009;48(10):1304–8. Scholar
  256. 256.
    Ryan JG, de Koning HD, Beck LA, Booty MG, Kastner DL, Simon A. IL-1 blockade in Schnitzler syndrome: ex vivo findings correlate with clinical remission. J Allergy Clin Immunol. 2008;121(1):260–2. Scholar
  257. 257.
    de Koning HD, Bodar EJ, Simon A, van der Hilst JC, Netea MG, van der Meer JW. Beneficial response to anakinra and thalidomide in Schnitzler’s syndrome. Ann Rheum Dis. 2006;65(4):542–4. Scholar
  258. 258.
    Dybowski F, Sepp N, Bergerhausen HJ, Braun J. Successful use of anakinra to treat refractory Schnitzler’s syndrome. Clin Exp Rheumatol. 2008;26(2):354–7.PubMedGoogle Scholar
  259. 259.
    Sonnichsen A, Saulite I, Mangana J, Kerl K, Mehra T, Desislava I, et al. Interleukin-1 receptor antagonist (anakinra) for Schnitzler syndrome. The Journal of dermatological treatment. 2016;27(5):436–8. Scholar
  260. 260.
    Besada E, Nossent H. Dramatic response to IL1-RA treatment in longstanding multidrug resistant Schnitzler’s syndrome: a case report and literature review. Clin Rheumatol. 2010;29(5):567–71. Scholar
  261. 261.
    Krause K, Weller K, Stefaniak R, Wittkowski H, Altrichter S, Siebenhaar F, et al. Efficacy and safety of the interleukin-1 antagonist rilonacept in Schnitzler syndrome: an open-label study. Allergy. 2012;67(7):943–50. Scholar
  262. 262.
    de Koning HD, Schalkwijk J, van der Ven-Jongekrijg J, Stoffels M, van der Meer JW, Simon A. Sustained efficacy of the monoclonal anti-interleukin-1 beta antibody canakinumab in a 9-month trial in Schnitzler’s syndrome. Ann Rheum Dis. 2013;72(10):1634–8. Scholar
  263. 263.
    Krause K, Tsianakas A, Wagner N, Fischer J, Weller K, Metz M, et al. Efficacy and safety of canakinumab in Schnitzler syndrome: a multicenter randomized placebo-controlled study. J Allergy Clin Immunol. 2017;139(4):1311–20. Scholar
  264. 264.
    von den Driesch P. Sweet’s syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol. 1994;31(4):535-56; quiz 57-60.Google Scholar
  265. 265.
    Marzano AV, Borghi A, Wallach D, Cugno M. A comprehensive review of neutrophilic diseases. Clin Rev Allergy Immunol. 2018;54(1):114–30. Scholar
  266. 266.
    Smith SE, Gillon JT, Ferguson SB. Targetoid palmoplantar Sweet syndrome as presenting sign of severe Crohn’s disease. J Am Acad Dermatol. 2013;69(4):e199–200. Scholar
  267. 267.
    Tacke J, Diepgen TL, Albrecht HP, von den Driesch P. Idiopathic pustular and bullous variants of Sweet syndrome. Der Hautarzt Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 1994;45(3):184–7.CrossRefPubMedGoogle Scholar
  268. 268.
    Surovy AM, Pelivani N, Hegyi I, Buettiker U, Beltraminelli H, Borradori L. Giant cellulitis-like Sweet syndrome, a new variant of neutrophilic dermatosis. JAMA Dermatol. 2013;149(1):79–83. Scholar
  269. 269.
    Kroshinsky D, Alloo A, Rothschild B, Cummins J, Tan J, Montecino R, et al. Necrotizing Sweet syndrome: a new variant of neutrophilic dermatosis mimicking necrotizing fasciitis. J Am Acad Dermatol. 2012;67(5):945–54. Scholar
  270. 270.
    Galaria NA, Junkins-Hopkins JM, Kligman D, James WD. Neutrophilic dermatosis of the dorsal hands: pustular vasculitis revisited. J Am Acad Dermatol. 2000;43(5 Pt 1):870–4. Scholar
  271. 271.
    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. Scholar
  272. 272.
    Imhof L, Meier B, Frei P, Kamarachev J, Rogler G, Kolios A, et al. Severe Sweet’s syndrome with elevated cutaneous interleukin-1beta after azathioprine exposure: case report and review of the literature. Dermatology (Basel, Switzerland). 2015;230(4):293–8. Scholar
  273. 273.
    Delluc A, Limal N, Puechal X, Frances C, Piette JC, Cacoub P. Efficacy of anakinra, an IL1 receptor antagonist, in refractory Sweet syndrome. Ann Rheum Dis. 2008;67(2):278–9. Scholar
  274. 274.
    Kluger N, Gil-Bistes D, Guillot B, Bessis D. Efficacy of anti-interleukin-1 receptor antagonist anakinra (Kineret(R)) in a case of refractory Sweet’s syndrome. Dermatology (Basel, Switzerland). 2011;222(2):123–7. Scholar
  275. 275.
    Agarwal A, Barrow W, Selim MA, Nicholas MW. Refractory subcutaneous Sweet syndrome treated with adalimumab. JAMA Dermatol. 2016;152(7):842–4. Scholar
  276. 276.
    Karamlou K, Gorn AH. Refractory sweet syndrome with autoimmune organizing pneumonia treated with monoclonal antibodies to tumor necrosis factor. J Clin Rheumatol. 2004;10(6):331–5. Scholar
  277. 277.
    Yamauchi PS, Turner L, Lowe NJ, Gindi V, Jackson JM. Treatment of recurrent Sweet’s syndrome with coexisting rheumatoid arthritis with the tumor necrosis factor antagonist etanercept. J Am Acad Dermatol. 2006;54(3 Suppl 2):S122–6. Scholar
  278. 278.
    Ambrose NL, Tobin AM, Howard D. Etanercept treatment in Sweet’s syndrome with inflammatory arthritis. J Rheumatol. 2009;36(6):1348–9. Scholar
  279. 279.
    Foster EN, Nguyen KK, Sheikh RA, Prindiville TP. Crohn’s disease associated with Sweet’s syndrome and Sjogren’s syndrome treated with infliximab. Clin Dev Immunol. 2005;12(2):145–9.CrossRefPubMedPubMedCentralGoogle Scholar
  280. 280.
    Kolios AG, Maul JT, Meier B, Kerl K, Traidl-Hoffmann C, Hertl M, et al. Canakinumab in adults with steroid-refractory pyoderma gangrenosum. Br J Dermatol. 2015;173(5):1216–23. Scholar
  281. 281.
    Cugno M, Borghi A, Marzano AV. PAPA, PASH and PAPASH syndromes: pathophysiology, presentation and treatment. Am J Clin Dermatol. 2017;18(4):555–62. Scholar
  282. 282.
    Maverakis E, Ma C, Shinkai K, Fiorentino D, Callen JP, Wollina U, et al. Diagnostic criteria of ulcerative pyoderma gangrenosum: a Delphi consensus of international experts. JAMA Dermatol. 2018;154(4):461–6. Scholar
  283. 283.
    Bhatti H, Khalid N, Rao B. Superficial pyoderma gangrenosum treated with infliximab: a case report. Cutis. 2012;90(6):297–9.PubMedGoogle Scholar
  284. 284.
    Kouklakis G, Moschos J, Leontiadis GI, Kadis S, Mpoumponaris A, Molyvas E, et al. Infliximab for treatment of pyoderma gangrenosum associated with clinically inactive Crohn’s disease. A case report. Rom J Gastroenterol. 2005;14(4):401–3.PubMedGoogle Scholar
  285. 285.
    Adisen E, Oztas M, Gurer MA. Treatment of idiopathic pyoderma gangrenosum with infliximab: Induction dosing regimen or on-demand therapy? Dermatology (Basel, Switzerland). 2008;216(2):163–5. Scholar
  286. 286.
    Brooklyn TN, Dunnill MG, Shetty A, Bowden JJ, Williams JD, Griffiths CE, et al. Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut. 2006;55(4):505–9. Scholar
  287. 287.
    Agarwal A, Andrews JM. Systematic review: IBD-associated pyoderma gangrenosum in the biologic era, the response to therapy. Aliment Pharmacol Ther. 2013;38(6):563–72. Scholar
  288. 288.
    Carrasco Cubero C, Ruiz Tudela MM, Salaberri Maestrojuan JJ, Perez Venegas JJ. Pyoderma gangrenosum associated with inflammatory bowel disease. Report of two cases with good response to infliximab. Reumatol Clin. 2012;8(2):90–2. Scholar
  289. 289.
    Teich N, Klugmann T. Rapid improvement of refractory pyoderma gangrenosum with infliximab gel in a patient with ulcerative colitis. J Crohn’s Colitis. 2014;8(1):85–6. Scholar
  290. 290.
    McGowan JWT, Johnson CA, Lynn A. Treatment of pyoderma gangrenosum with etanercept. J Drugs In Dermatol JDD. 2004;3(4):441–4.Google Scholar
  291. 291.
    Charles CA, Leon A, Banta MR, Kirsner RS. Etanercept for the treatment of refractory pyoderma gangrenosum: a brief series. Int J Dermatol. 2007;46(10):1095–9. Scholar
  292. 292.
    Heffernan MP, Anadkat MJ, Smith DI. Adalimumab treatment for pyoderma gangrenosum. Arch Dermatol. 2007;143(3):306–8. Scholar
  293. 293.
    Kleinpenning MM, Langewouters AM, Van De Kerkhof PC, Greebe RJ. Severe pyoderma gangrenosum unresponsive to etanercept and adalimumab. J Dermatol Trea. 2011;22(5):261–5. Scholar
  294. 294. Identifier NCT03311464. A phase 3 multicenter, open-label, single arm study of the efficacy and safety of adalimumab in active ulcer(s) of pyoderma gangrenosum in subjects in Japan. Accessed 10 Dec 2018.
  295. 295.
    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(10):1203–5. Scholar
  296. 296.
    Goldminz AM, Botto NC, Gottlieb AB. Severely recalcitrant pyoderma gangrenosum successfully treated with ustekinumab. J Am Acad Dermatol. 2012;67(5):e237–8. Scholar
  297. 297.
    Fahmy M, Ramamoorthy S, Hata T, Sandborn WJ. Ustekinumab for peristomal pyoderma gangrenosum. Am J Gastroenterol. 2012;107(5):794–5. Scholar
  298. 298.
    Greb JE, Gottlieb AB, Goldminz AM. High-dose ustekinumab for the treatment of severe, recalcitrant pyoderma gangrenosum. Dermatol Ther. 2016;29(6):482–3. Scholar
  299. 299.
    Low ZM, Mar A. Treatment of severe recalcitrant pyoderma gangrenosum with ustekinumab. Australas J Dermatol. 2018;59(2):131–4. Scholar
  300. 300.
    Galimberti RL, Vacas AS, Bollea Garlatti ML, Torre AC. The role of interleukin-1beta in pyoderma gangrenosum. JAAD Case Rep. 2016;2(5):366–8. Scholar
  301. 301.
    Acquitter M, Plantin P, Kupfer I, Auvinet H, Marhadour T. Anakinra improves pyoderma gangrenosum in psoriatic arthritis: a case report. Ann Intern Med. 2015;163(1):70–1. Scholar
  302. 302.
    Beynon C, Chin MF, Hunasehally P, Bhagwandas K, Bevan M, Taylor M, et al. Successful treatment of autoimmune disease-associated pyoderma gangrenosum with the IL-1 receptor antagonist anakinra: a case series of 3 patients. J Clin Rheumatol. 2017;23(3):181–3. Scholar
  303. 303.
    Mercuri SR, Paolino G, De Flammineis E, Didona D, Brianti P. Successful treatment of pyoderma gangrenosum with anakinra in a patient with Wiskott-Aldrich syndrome. Dermatol Ther. 2018;31(2):e12582. Scholar
  304. 304.
    Carlstrom M, Ekman AK, Petersson S, Soderkvist P, Enerback C. Genetic support for the role of the NLRP3 inflammasome in psoriasis susceptibility. Exp Dermatol. 2012;21(12):932–7. Scholar
  305. 305.
    Ekman AK, Verma D, Fredrikson M, Bivik C, Enerback C. Genetic variations of NLRP1: susceptibility in psoriasis. Br J Dermatol. 2014;171(6):1517–20. Scholar
  306. 306.
    Johansen C, Moeller K, Kragballe K, Iversen L. The activity of caspase-1 is increased in lesional psoriatic epidermis. J Invest Dermatol. 2007;127(12):2857–64. Scholar
  307. 307.
    Wang M, Zhang S, Zheng G, Huang J, Songyang Z, Zhao X, et al. Gain-of-function mutation of Card14 leads to spontaneous psoriasis-like skin inflammation through enhanced keratinocyte response to IL-17A. Immunity. 2018;49(1):66–79.e5. Scholar
  308. 308.
    Gonzalez-Lara L, Coto-Segura P, Penedo A, Eiris N, Diaz M, Santos-Juanes J, et al. SNP rs11652075 in the CARD14 gene as a risk factor for psoriasis (PSORS2) in a Spanish cohort. DNA Cell Biol. 2013;32(10):601–4. Scholar
  309. 309.
    Shi G, Li SJ, Wang TT, Cheng CM, Fan YM, Zhu KJ. The common CARD14 gene missense polymorphism rs11652075 (c.C2458T/p.Arg820Trp) is associated with psoriasis: a meta-analysis. Genet Mol Res GMR. 2016;15(3):15. Scholar
  310. 310.
    Takeichi T, Kobayashi A, Ogawa E, Okuno Y, Kataoka S, Kono M, et al. Autosomal dominant familial generalized pustular psoriasis caused by a CARD14 mutation. Br J Dermatol. 2017;177(4):e133–5. Scholar
  311. 311.
    Zhu K, Shi G, Liu H, Zhu C, Fan Y. Variants of CARD14 gene and psoriasis vulgaris in southern Chinese cohort. Anais Bras Dermatol. 2016;91(1):45–8. Scholar
  312. 312.
    Liang Y, Sarkar MK, Tsoi LC, Gudjonsson JE. Psoriasis: a mixed autoimmune and autoinflammatory disease. Curr Opin Immunol. 2017;49:1–8. Scholar
  313. 313.
    Tsai Y-C, Tsai T-F. Anti-interleukin and interleukin therapies for psoriasis: current evidence and clinical usefulness. Ther Adv Musculoskelet Dis. 2017;9(11):277–94. Scholar
  314. 314.
    Kistowska M, Gehrke S, Jankovic D, Kerl K, Fettelschoss A, Feldmeyer L, et al. IL-1beta drives inflammatory responses to Propionibacterium acnes in vitro and in vivo. J Invest Dermatol. 2014;134(3):677–85. Scholar
  315. 315.
    Qin M, Pirouz A, Kim MH, Krutzik SR, Garban HJ, Kim J. Propionibacterium acnes induces IL-1beta secretion via the NLRP3 inflammasome in human monocytes. J Invest Dermatol. 2014;134(2):381–8. Scholar
  316. 316.
    Xoma. XOMA announces encouraging interim results from gevokizumab phase 2 study for moderate to severe acne vulgaris. 2013. Accessed 11 Apr 2019.
  317. 317.
    Qin M, Landriscina A, Rosen JM, Wei G, Kao S, Olcott W, et al. Nitric oxide-releasing nanoparticles prevent Propionibacterium acnes-induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response. J Invest Dermatol. 2015;135(11):2723–31. Scholar
  318. 318.
    Baldwin H, Blanco D, McKeever C, Paz N, Vasquez YN, Quiring J, et al. Results of a phase 2 efficacy and safety study with SB204, an investigational topical nitric oxide-releasing drug for the treatment of acne vulgaris. J Clin Aesth Dermatol. 2016;9(8):12–8.Google Scholar
  319. 319.
    Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357–61. Scholar
  320. 320.
    Masters SL, Dunne A, Subramanian SL, Hull RL, Tannahill GM, Sharp FA, et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1beta in type 2 diabetes. Nat Immunol. 2010;11(10):897–904. Scholar
  321. 321.
    Salminen A, Kaarniranta K, Kauppinen A. Inflammaging: disturbed interplay between autophagy and inflammasomes. Aging. 2012;4(3):166–75. Scholar
  322. 322.
    Haneklaus M, O’Neill LA. NLRP3 at the interface of metabolism and inflammation. Immunol Rev. 2015;265(1):53–62. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.The Warren Alpert Medical School of Brown UniversityProvidenceUSA
  2. 2.Icahn School of Medicine at Mount SinaiNew YorkUSA

Personalised recommendations