Pustular Psoriasis

  • Andrew JohnstonEmail author


Pustular forms of psoriasis are a group of rare, debilitating, and often life-threatening inflammatory skin diseases characterized by episodic skin infiltration of neutrophils, pustule development, erythema and desquamation, which can manifest in the presence or absence of chronic plaque psoriasis. The skin involvement is frequently accompanied by a high-grade fever, fatigue and systemic inflammation. Despite having different genetic and environmental etiologies generalized pustular psoriasis (GPP), acute generalized exanthemous pustulosis (AGEP), palmo-plantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH) are all characterized by a massive influx of neutrophils into the epidermis, thus share some mechanistic aspects. To date, treatments for these diseases have been unsatisfactory with disease recurrence common; however, recent genetic data and ongoing clinical trials with biologic therapies are revealing hitherto unknown mechanisms, substantially improving our understanding and management of these diseases.


  1. 1.
    Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2012;133:377–85.PubMedCrossRefGoogle Scholar
  2. 2.
    Di Meglio P, Villanova F, Nestle FO. Psoriasis. Cold Spring Harb Perspect Med. 2014;4(8).Google Scholar
  3. 3.
    von Zumbush L. Psoriasis and pustuloses exanthem. Arch Derm Syph. 1910;99:335–46.CrossRefGoogle Scholar
  4. 4.
    Mengesha YM, Bennett ML. Pustular skin disorders: diagnosis and treatment. Am J Clin Dermatol. 2002;3:389–400.PubMedCrossRefGoogle Scholar
  5. 5.
    Gudjonsson JE, Elder JT. Psoriasis (Chapter 18). In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors. Fitzpatrick’s dermatology in general medicine, vol. 1. 8th ed. New York: McGraw-Hill Medical; 2012.Google Scholar
  6. 6.
    Robinson A, Van Voorhees AS, Hsu S, et al. Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2012;67:279–88.PubMedCrossRefGoogle Scholar
  7. 7.
    Johnston A, Xing X, Wolterink L, et al. IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis. J Allergy Clin Immunol. 2016;140(1):109–20.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Liang Y, Xing X, Beamer MA, et al. Six-transmembrane epithelial antigens of the prostate comprise a novel inflammatory nexus in patients with pustular skin disorders. J Allergy Clin Immunol. 2017;139(4):1217–27.PubMedCrossRefGoogle Scholar
  9. 9.
    Sidoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized exanthematous pustulosis (AGEP)—a clinical reaction pattern. J Cutan Pathol. 2001;28:113–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Szatkowski J, Schwartz RA. Acute generalized exanthematous pustulosis (AGEP): a review and update. J Am Acad Dermatol. 2015;73:843–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Sidoroff A, Dunant A, Viboud C, et al. Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR). Br J Dermatol. 2007;157:989–96.PubMedCrossRefGoogle Scholar
  12. 12.
    Mockenhaupt M, Viboud C, Dunant A, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol. 2008;128:35–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Paulmann M, Mockenhaupt M. Severe drug hypersensitivity reactions: clinical pattern, diagnosis, etiology and therapeutic options. Curr Pharm Des. 2016;22:6852–61.PubMedCrossRefGoogle Scholar
  14. 14.
    Schmid S, Kuechler PC, Britschgi M, et al. Acute generalized exanthematous pustulosis: role of cytotoxic T cells in pustule formation. Am J Pathol. 2002;161:2079–86.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Navarini AA, Valeyrie-Allanore L, Setta-Kaffetzi N, et al. Rare variations in IL36RN in severe adverse drug reactions manifesting as acute generalized exanthematous pustulosis. J Invest Dermatol. 2013;133:1904–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Nakai N, Sugiura K, Akiyama M, Katoh N. Acute generalized exanthematous pustulosis caused by dihydrocodeine phosphate in a patient with psoriasis vulgaris and a heterozygous IL36RN mutation. JAMA Dermatol. 2015;151:311–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Setta-Kaffetzi N, Navarini AA, Patel VM, et al. Rare pathogenic variants in IL36RN underlie a spectrum of psoriasis-associated pustular phenotypes. J Invest Dermatol. 2013;133:1366–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Oumeish OY, Parish JL. Impetigo herpetiformis. Clin Dermatol. 2006;24:101–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Chung J, Callis Duffin K, Takeshita J, et al. Palmoplantar psoriasis is associated with greater impairment of health-related quality of life compared with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2014;71:623–32.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Pettey AA, Balkrishnan R, Rapp SR, Fleischer AB, Feldman SR. Patients with palmoplantar psoriasis have more physical disability and discomfort than patients with other forms of psoriasis: implications for clinical practice. J Am Acad Dermatol. 2003;49:271–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Hellgren L, Mobacken H. Pustulosis palmaris et plantaris. Prevalence, clinical observations and prognosis. Acta Derm Venereol. 1971;51:284–8.PubMedGoogle Scholar
  22. 22.
    Brunasso AM, Puntoni M, Aberer W, Delfino C, Fancelli L, Massone C. Clinical and epidemiological comparison of patients affected by palmoplantar plaque psoriasis and palmoplantar pustulosis: a case series study. Br J Dermatol. 2013;168:1243–51.PubMedCrossRefGoogle Scholar
  23. 23.
    Mossner R, Frambach Y, Wilsmann-Theis D, 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;135:2538–41.PubMedCrossRefGoogle Scholar
  24. 24.
    Asumalahti K, Ameen M, Suomela S, et al. Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis. J Invest Dermatol. 2003;120:627–32.PubMedCrossRefGoogle Scholar
  25. 25.
    Mossner R, Kingo K, Kleensang A, et al. Association of TNF-238 and -308 promoter polymorphisms with psoriasis vulgaris and psoriatic arthritis but not with pustulosis palmoplantaris. J Invest Dermatol. 2005;124:282–4.PubMedCrossRefGoogle Scholar
  26. 26.
    Mahil SK, Twelves S, Farkas K, et al. AP1S3 mutations cause skin autoinflammation by disrupting keratinocyte autophagy and up-regulating IL-36 production. J Invest Dermatol. 2016;136:2251–9.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Griffiths CE, Christophers E, Barker JN, et al. A classification of psoriasis vulgaris according to phenotype. Br J Dermatol. 2007;156:258–62.PubMedCrossRefGoogle Scholar
  28. 28.
    Krieg PH, Bacharach-Buhles M, el-Gammal S, Altmeyer P. The pustule in palmoplantar psoriasis: transformed vesicle or mature microabscess? A three-dimensional study. Dermatology. 1992;185:104–12.PubMedCrossRefGoogle Scholar
  29. 29.
    Eriksson MO, Hagforsen E, Lundin IP, Michaelsson G. Palmoplantar pustulosis: a clinical and immunohistological study. Br J Dermatol. 1998;138:390–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Murakami M, Ohtake T, Horibe Y, et al. Acrosyringium is the main site of the vesicle/pustule formation in palmoplantar pustulosis. J Invest Dermatol. 2010;130:2010–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Hagforsen E, Awder M, Lefvert AK, Nordlind K, Michaelsson G. Palmoplantar pustulosis: an autoimmune disease precipitated by smoking? Acta Derm Venereol. 2002;82:341–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Yoshizaki T, Bandoh N, Ueda S, et al. Up-regulation of CC chemokine receptor 6 on tonsillar T cells and its induction by in vitro stimulation with alpha-streptococci in patients with pustulosis palmaris et plantaris. Clin Exp Immunol. 2009;157:71–82.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Nozawa H, Kishibe K, Takahara M, Harabuchi Y. Expression of cutaneous lymphocyte-associated antigen (CLA) in tonsillar T-cells and its induction by in vitro stimulation with alpha-streptococci in patients with pustulosis palmaris et plantaris (PPP). Clin Immunol. 2005;116:42–53.PubMedCrossRefGoogle Scholar
  34. 34.
    Valdimarsson H, Thorleifsdottir RH, Sigurdardottir SL, Gudjonsson JE, Johnston A. Psoriasis—as an autoimmune disease caused by molecular mimicry. Trends Immunol. 2009;30:494–501.PubMedCrossRefGoogle Scholar
  35. 35.
    Thorleifsdottir RH, Sigurdardottir SL, Sigurgeirsson B, et al. HLA-Cw6 homozygosity in plaque psoriasis is associated with streptococcal throat infections and pronounced improvement after tonsillectomy: a prospective case series. J Am Acad Dermatol. 2016;75:889–96.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Thorleifsdottir RH, Sigurdardottir SL, Sigurgeirsson B, et al. Improvement of psoriasis after tonsillectomy is associated with a decrease in the frequency of circulating T cells that recognize streptococcal determinants and homologous skin determinants. J Immunol. 2012;188:5160–5.CrossRefPubMedGoogle Scholar
  37. 37.
    Koshiba S, Ichimiya S, Nagashima T, et al. Tonsillar crypt epithelium of palmoplantar pustulosis secretes interleukin-6 to support B-cell development via p63/p73 transcription factors. J Pathol. 2008;214:75–84.CrossRefPubMedGoogle Scholar
  38. 38.
    Yokoyama M, Hashigucci K, Yamasaki Y. Effect of tonsillectomy in patients with pustulosis palmaris et plantaris. Acta Otolaryngol. 2004;124:1109–10.CrossRefPubMedGoogle Scholar
  39. 39.
    Ozawa A, Ohkido M, Haruki Y, et al. Treatments of generalized pustular psoriasis: a multicenter study in Japan. J Dermatol. 1999;26:141–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365:620–8.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Onoufriadis A, Simpson MA, Pink AE, et al. Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am J Hum Genet. 2011;89:432–7.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Navarini AA, Simpson MA, Borradori L, Yawalkar N, Schlapbach C. Homozygous missense mutation in IL36RN in generalized pustular dermatosis with intraoral involvement compatible with both AGEP and generalized pustular psoriasis. JAMA Dermatol. 2015;151:452–3.PubMedCrossRefGoogle Scholar
  43. 43.
    Takahashi T, Fujimoto N, Kabuto M, Nakanishi T, Tanaka T. Mutation analysis of IL36RN gene in Japanese patients with palmoplantar pustulosis. J Dermatol. 2017;44:80–3.PubMedCrossRefGoogle Scholar
  44. 44.
    Johnston A, Xing X, Guzman AM, et al. IL-1F5, -F6, -F8, and -F9: a novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression. J Immunol. 2011;186:2613–22.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Blumberg H, Dinh H, Trueblood ES, et al. Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation. J Exp Med. 2007;204:2603–14.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Debets R, Timans JC, Homey B, et al. Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2. J Immunol. 2001;167:1440–6.PubMedCrossRefGoogle Scholar
  47. 47.
    Carrier Y, Ma HL, Ramon HE, et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. J Invest Dermatol. 2011;131:2428–37.PubMedCrossRefGoogle Scholar
  48. 48.
    Foster AM, Baliwag J, Chen CS, et al. IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin. J Immunol. 2014;192:6053–61.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Mutamba S, Allison A, Mahida Y, Barrow P, Foster N. Expression of IL-1Rrp2 by human myelomonocytic cells is unique to DCs and facilitates DC maturation by IL-1F8 and IL-1F9. Eur J Immunol. 2012;42:607–17.PubMedCrossRefGoogle Scholar
  50. 50.
    Tortola L, Rosenwald E, Abel B, et al. Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk. J Clin Invest. 2012;122:3965–76.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Towne JE, Renshaw BR, Douangpanya J, et al. Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36{alpha}, IL-36{beta} and IL-36{gamma}) or antagonist (IL-36Ra) activity. J Biol Chem. 2011;286:42594–602.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Henry CM, Sullivan GP, Clancy DM, Afonina IS, Kulms D, Martin SJ. Neutrophil-derived proteases escalate inflammation through activation of IL-36 family cytokines. Cell Rep. 2016;14:708–22.PubMedCrossRefGoogle Scholar
  53. 53.
    Ainscough JS, Macleod T, McGonagle D, et al. Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36gamma. Proc Natl Acad Sci U S A. 2017;114(13):E2748–57.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Korber A, Mossner R, Renner R, et al. Mutations in IL36RN in patients with generalized pustular psoriasis. J Invest Dermatol. 2013;133:2634–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Sugiura K, Takemoto A, Yamaguchi M, et al. The majority of generalized pustular psoriasis without psoriasis vulgaris is caused by deficiency of interleukin-36 receptor antagonist. J Invest Dermatol. 2013;133:2514–21.PubMedCrossRefGoogle Scholar
  56. 56.
    Hussain S, Berki DM, Choon SE, et al. IL36RN mutations define a severe autoinflammatory phenotype of generalized pustular psoriasis. J Allergy Clin Immunol. 2015;135:1067–1070 e1069.PubMedCrossRefGoogle Scholar
  57. 57.
    Setta-Kaffetzi N, Simpson MA, Navarini AA, et al. AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking. Am J Hum Genet. 2014;94(5):790–7.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Robinson MS. Adaptable adaptors for coated vesicles. Trends Cell Biol. 2004;14:167–74.PubMedCrossRefGoogle Scholar
  59. 59.
    Nakatsu F, Hase K, Ohno H. The role of the clathrin adaptor AP-1: polarized sorting and beyond. Membranes (Basel). 2014;4:747–3.CrossRefGoogle Scholar
  60. 60.
    Jordan CT, Cao L, Roberson ED, et al. PSORS2 is due to mutations in CARD14. Am J Hum Genet. 2012;90:784–95.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Jordan CT, Cao L, Roberson ED, et al. Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis. Am J Hum Genet. 2012;90:796–808.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Berki DM, Liu L, Choon SE, et al. Activating CARD14 mutations are associated with generalized pustular psoriasis but rarely account for familial recurrence in psoriasis vulgaris. J Invest Dermatol. 2015;135:2964–70.PubMedCrossRefGoogle Scholar
  63. 63.
    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 Invest Dermatol. 2014;134:1755–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Li Q, Jin Chung H, Ross N, et al. Analysis of CARD14 polymorphisms in pityriasis rubra pilaris: activation of NF-kappaB. J Invest Dermatol. 2015;135:1905–8.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Fuchs-Telem D, Sarig O, van Steensel MA, et al. Familial pityriasis rubra pilaris is caused by mutations in CARD14. Am J Hum Genet. 2012;91:163–70.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Afonina IS, Van Nuffel E, Baudelet G, et al. The paracaspase MALT1 mediates CARD14-induced signaling in keratinocytes. EMBO Rep. 2016;17:914–27.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Scudiero I, Zotti T, Ferravante A, Vessichelli M, Vito P, Stilo R. Alternative splicing of CARMA2/CARD14 transcripts generates protein variants with differential effect on NF-kappaB activation and endoplasmic reticulum stress-induced cell death. J Cell Physiol. 2011;226:3121–31.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Howes A, O’Sullivan PA, Breyer F, et al. Psoriasis mutations disrupt CARD14 autoinhibition promoting BCL10-MALT1-dependent NF-kappaB activation. Biochem J. 2016;473:1759–68.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Van Nuffel E, Schmitt A, Afonina IS, Schulze-Osthoff K, Beyaert R, Hailfinger S. CARD14-mediated activation of paracaspase MALT1 in keratinocytes: implications for psoriasis. J Invest Dermatol. 2017;137:569–75.PubMedCrossRefGoogle Scholar
  70. 70.
    Harden JL, Lewis SM, Pierson KC, et al. CARD14 expression in dermal endothelial cells in psoriasis. PLoS One. 2014;9:e111255.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Rossi-Semerano L, Piram M, Chiaverini C, De Ricaud D, Smahi A, Kone-Paut I. First clinical description of an infant with interleukin-36-receptor antagonist deficiency successfully treated with anakinra. Pediatrics. 2013;132:e1043–7.PubMedCrossRefGoogle Scholar
  72. 72.
    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;170:202–4.PubMedCrossRefGoogle Scholar
  73. 73.
    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;153:66–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Skendros P, Papagoras C, Lefaki I, et al. Successful response in a case of severe pustular psoriasis after interleukin-1beta inhibition. Br J Dermatol. 2017;176:212–5.PubMedCrossRefGoogle Scholar
  75. 75.
    Tauber M, Viguier M, Le Gall C, Smahi A, Bachelez H. Is it relevant to use an interleukin-1-inhibiting strategy for the treatment of patients with deficiency of interleukin-36 receptor antagonist? Br J Dermatol. 2014;170:1198–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Elewski BE. Infliximab for the treatment of severe pustular psoriasis. J Am Acad Dermatol. 2002;47:796–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Newland MR, Weinstein A, Kerdel F. Rapid response to infliximab in severe pustular psoriasis, von Zumbusch type. Int J Dermatol. 2002;41:449–52.PubMedCrossRefGoogle Scholar
  78. 78.
    Johnston A, Guzman AM, Swindell WR, Wang F, Kang S, Gudjonsson JE. Early tissue responses in psoriasis to the antitumour necrosis factor-alpha biologic etanercept suggest reduced interleukin-17 receptor expression and signalling. Br J Dermatol. 2014;171:97–107.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Chiricozzi A, Guttman-Yassky E, Suarez-Farinas M, et al. Integrative responses to IL-17 and TNF-alpha in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol. 2011;131:677–87.PubMedCrossRefGoogle Scholar
  80. 80.
    Yilmaz SB, Cicek N, Coskun M, Yegin O, Alpsoy E. Serum and tissue levels of IL-17 in different clinical subtypes of psoriasis. Arch Dermatol Res. 2012;304:465–9.PubMedCrossRefGoogle Scholar
  81. 81.
    Teraki Y, Tanaka S, Hitomi K, Izaki S. A case of generalized psoriasiform and pustular eruption induced by infliximab: evidence for skin-homing Th17 in the pathogenesis. Br J Dermatol. 2010;163:1347–51.PubMedCrossRefGoogle Scholar
  82. 82.
    Kakeda M, Schlapbach C, Danelon G, et al. Innate immune cells express IL-17A/F in acute generalized exanthematous pustulosis and generalized pustular psoriasis. Arch Dermatol Res. 2014;306:933–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Khemis A, Cavalie M, Montaudie H, Lacour JP, Passeron T. Rebound pustular psoriasis after brodalumab discontinuation. Br J Dermatol. 2016;175:1065–6.PubMedCrossRefGoogle Scholar
  84. 84.
    Girolomoni G, Mrowietz U, Paul C. Psoriasis: rationale for targeting interleukin-17. Br J Dermatol. 2012;167:717–4.PubMedCrossRefGoogle Scholar
  85. 85.
    Lin AM, Rubin CJ, Khandpur R, et al. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol. 2011;187:490–500.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Keijsers RR, Hendriks AG, van Erp PE, et al. In vivo induction of cutaneous inflammation results in the accumulation of extracellular trap-forming neutrophils expressing RORgammat and IL-17. J Invest Dermatol. 2014;134:1276–84.PubMedCrossRefGoogle Scholar
  87. 87.
    Taylor PR, Roy S, Leal SM Jr, et al. Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORgammat and dectin-2. Nat Immunol. 2014;15:143–51.PubMedCrossRefGoogle Scholar
  88. 88.
    Bohner A, Roenneberg S, Eyerich K, Eberlein B, Biedermann T. Acute generalized pustular psoriasis treated with the IL-17A antibody secukinumab. JAMA Dermatol. 2015;152(4):482–4.CrossRefGoogle Scholar
  89. 89.
    Imafuku S, Honma M, Okubo Y, 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;43:1011–7.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Gottlieb A, Sullivan J, van Doorn M, et al. Secukinumab shows significant efficacy in palmoplantar psoriasis: results from GESTURE, a randomized controlled trial. J Am Acad Dermatol. 2017;76:70–80.PubMedCrossRefGoogle Scholar
  91. 91.
    Yamasaki K, Nakagawa H, Kubo Y, Ootaki K, Japanese brodalumab study g. 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;176:741–51.PubMedCrossRefGoogle Scholar
  92. 92.
    Di Meglio P, Nestle FO. The role of IL-23 in the immunopathogenesis of psoriasis. F1000 Biol Rep. 2010;2:40.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Langrish CL, McKenzie BS, Wilson NJ, de Waal MR, Kastelein RA, Cua DJ. IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev. 2004;202:96–105.PubMedCrossRefGoogle Scholar
  94. 94.
    Wolf J, Ferris LK. Anti-IL-36R antibodies, potentially useful for the treatment of psoriasis: a patent evaluation of WO2013074569. Expert Opin Ther Pat. 2014;24:477–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Gunther S, Sundberg EJ. Molecular determinants of agonist and antagonist signaling through the IL-36 receptor. J Immunol. 2014;193:921–30.PubMedCrossRefGoogle Scholar
  96. 96.
    Bissonnette R, Poulin Y, Guenther L, Lynde CW, Bolduc C, Nigen S. Treatment of palmoplantar psoriasis with infliximab: a randomized, double-blind placebo-controlled study. J Eur Acad Dermatol Venereol. 2011;25:1402–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Bissonnette R, Poulin Y, Bolduc C, et al. Etanercept in the treatment of palmoplantar pustulosis. J Drugs Dermatol. 2008;7:940–6.PubMedGoogle Scholar
  98. 98.
    Leonardi C, Langley RG, Papp K, et al. Adalimumab for treatment of moderate to severe chronic plaque psoriasis of the hands and feet: efficacy and safety results from REACH, a randomized, placebo-controlled, double-blind trial. Arch Dermatol. 2011;147:429–36.PubMedCrossRefGoogle Scholar
  99. 99.
    Tresh A, Smith VH, Parslew RA. Behcet’s syndrome treated with infliximab, which caused a palmoplantar pustulosis, subsequently maintained on low-dose etanercept. Libyan J Med. 2012; 7.Google Scholar
  100. 100.
    Capkin E, Karkucak M, Yayli S, Aydin Capkin A, Tosun M. Infliximab-induced palmoplantar psoriasis in a patient with ankylosing spondylitis. J Clin Rheumatol. 2011;17:293–4.PubMedCrossRefGoogle Scholar
  101. 101.
    Wermuth J, Kind F, Steuerwald M. Palmoplantar pustulosis and acrodermatitis in a patient treated with infliximab for Crohn’s sacroiliitis. Clin Gastroenterol Hepatol. 2009;7:A28.PubMedCrossRefGoogle Scholar
  102. 102.
    Ortiz Salvador JM, Cubells Sanchez L, Subiabre Ferrer D. Palmoplantar pustulosis by adalimumab in a patient with Crohn disease. Med Clin (Barc). 2016;147:565.CrossRefGoogle Scholar
  103. 103.
    Rallis E, Korfitis C, Stavropoulou E, Papaconstantis M. Onset of palmoplantar pustular psoriasis while on adalimumab for psoriatic arthritis: a ‘class effect’ of TNF-alpha antagonists or simply an anti-psoriatic treatment adverse reaction? J Dermatolog Treat. 2010;21:3–5.PubMedCrossRefGoogle Scholar
  104. 104.
    Gerdes S, Franke J, Domm S, Mrowietz U. Ustekinumab in the treatment of palmoplantar pustulosis. Br J Dermatol. 2010;163:1116–8.PubMedCrossRefGoogle Scholar
  105. 105.
    Au SC, Goldminz AM, Kim N, et al. Investigator-initiated, open-label trial of ustekinumab for the treatment of moderate-to-severe palmoplantar psoriasis. J Dermatolog Treat. 2013;24:179–87.PubMedCrossRefGoogle Scholar
  106. 106.
    Buder V, Herberger K, Jacobi A, Augustin M, Radtke MA. Ustekinumab in the treatment of palmoplantar pustular psoriasis—a case series of nine patients. JDDG. 2016;14:1108–13.PubMedCrossRefGoogle Scholar
  107. 107.
    Arakawa A, Ruzicka T, Prinz JC. Therapeutic efficacy of interleukin 12/interleukin 23 blockade in generalized pustular psoriasis regardless of IL36RN mutation status. JAMA Dermatol. 2016;152:825–8.PubMedCrossRefGoogle Scholar
  108. 108.
    Murakami M, Hagforsen E, Morhenn V, Ishida-Yamamoto A, Iizuka H. Patients with palmoplantar pustulosis have increased IL-17 and IL-22 levels both in the lesion and serum. Exp Dermatol. 2011;20:845–7.PubMedCrossRefGoogle Scholar
  109. 109.
    Bissonnette R, Nigen S, Langley RG, et al. Increased expression of IL-17A and limited involvement of IL-23 in patients with palmo-plantar (PP) pustular psoriasis or PP pustulosis; results from a randomised controlled trial. J Eur Acad Dermatol Venereol. 2014;28:1298–305.PubMedCrossRefGoogle Scholar
  110. 110.
    Lillis JV, Guo CS, Lee JJ, Blauvelt A. Increased IL-23 expression in palmoplantar psoriasis and hyperkeratotic hand dermatitis. Arch Dermatol. 2010;146:918–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of DermatologyUniversity of MichiganAnn ArborUSA

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