Advertisement

Pustular Forms of Psoriasis Related to Autoinflammation

  • Satveer K. Mahil
  • Jonathan N. Barker
  • Francesca CaponEmail author
Chapter

Abstract

Psoriasis is a common inflammatory skin disorder that is classified into multiple disease subtypes. The pustular variants, which are characterized by neutrophilic infiltrates, present with acute, potentially-life threatening episodes of pustulation and systemic upset (generalised pustular psoriasis, GPP) or with chronic and disabling pustulation of the hands and feet (palmar plantar pustulosis, PPP and acrodermatitis continua of Hallopeau, ACH). These are very severe conditions that are extremely difficult to treat.

In the last few years, genetic studies have identified three disease genes (IL36RN, AP1S3 and CARD14) that are mutated in one or more forms of pustular psoriasis. This has demonstrated a shared genetic basis for these conditions and highlighted an autoinflammatory pathogenesis, driven by abnormal IL-36 signalling. In this context, the ongoing development of IL-36 antagonists holds the promise of delivering efficient therapeutics for a group of diseases that have a profound impact on quality of life.

Keywords

Pustular psoriasis Interleukin-36 IL-36 IL36RN AP1S3 CARD14 Skin autoinflammation DITRA 

Abbreviations

ACH

Acrodermatitis continua of Hallopeau

CAMPS

CARD14 mediated psoriasis

DITRA

Deficiency of the interleukin 36 receptor antagonist

GPP

Generalised pustular psoriasis

IL-36Ra

Interleukin-36 receptor antagonist

PPP

Palmar plantar pustulosis.

References

  1. 1.
    Burden AD, Kirby B. Psoriasis and related disorders. In: Griffiths CEM, Barker JN, Bleiker T, Chalmers RJ, Creamer D, editors. Rook’s textbook of dermatology. Chichester: Wiley-Blackwell; 2016.Google Scholar
  2. 2.
    Augey F, Renaudier P, Nicolas JF. Generalized pustular psoriasis (Zumbusch): a French epidemiological survey. Eur J Dermatol. 2006;16(6):669–73.Google Scholar
  3. 3.
    Kawada A, Tezuka T, Nakamizo Y, Kimura H, Nakagawa H, Ohkido M, Ozawa A, Ohkawara A, Kobayashi H, Harada S, Igarashi A, Japanese Society for Psoriasis Research. A survey of psoriasis patients in Japan from 1982 to 2001. J Dermatol Sci. 2003;31(1):59–64.PubMedCrossRefGoogle Scholar
  4. 4.
    Lau BW, Lim DZ, Capon F, Barker JN, Choon SE. Juvenile generalized pustular psoriasis is a chronic recalcitrant disease: an analysis of 27 patients seen in a tertiary hospital in Johor, Malaysia. Int J Dermatol. 2017;56(4):392–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Posso-De Los Rios CJ, Pope E, Lara-Corrales I. A systematic review of systemic medications for pustular psoriasis in pediatrics. Pediatr Dermatol. 2014;31(4):430–9.PubMedCrossRefGoogle Scholar
  6. 6.
    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(6):1243–51.PubMedCrossRefGoogle Scholar
  7. 7.
    Kubota K, Kamijima Y, Sato T, Ooba N, Koide D, Iizuka H, Nakagawa H. Epidemiology of psoriasis and palmoplantar pustulosis: a nationwide study using the Japanese national claims database. BMJ open. 2015;5(1):e006450.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Hussain S, Berki DM, Choon SE, Burden AD, Allen MH, Arostegui JI, Chaves A, Duckworth M, Irvine AD, Mockenhaupt M, Navarini AA, Seyger MM, Soler-Palacin P, Prins C, Valeyrie-Allanore L, Vicente MA, Trembath RC, Smith CH, Barker JN, Capon F. IL36RN mutations define a severe auto-inflammatory phenotype of generalized pustular psoriasis. J Allergy Clin Immunol. 2015;135(4):1067–70.CrossRefGoogle Scholar
  9. 9.
    Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY, Fraitag S, Zribi J, Bal E, Cluzeau C, Chrabieh M, Towne JE, Douangpanya J, Pons C, Mansour S, Serre V, Makni H, Mahfoudh N, Fakhfakh F, Bodemer C, Feingold J, Hadj-Rabia S, Favre M, Genin E, Sahbatou M, Munnich A, Casanova JL, Sims JE, Turki H, Bachelez H, Smahi A. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365(7):620–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Onoufriadis A, Simpson MA, Pink AE, Di Meglio P, Smith CH, Pullabhatla V, Knight J, Spain SL, Nestle FO, Burden AD, Capon F, Trembath RC, Barker JN. Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am J Hum Genet. 2011;89(3):432–7. S0002-9297(11)00316-8 [pii].PubMedCrossRefGoogle Scholar
  11. 11.
    Setta-Kaffetzi N, Simpson MA, Navarini AA, Patel VM, Lu HC, Allen MH, Duckworth M, Bachelez H, Burden AD, Choon SE, Griffiths CE, Kirby B, Kolios A, Seyger MM, Prins C, Smahi A, Trembath RC, Fraternali F, Smith CH, Barker JN, Capon F. AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking. Am J Hum Genet. 2014;94(5):790–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Mahil SK, Twelves S, Farkas K, Setta-Kaffetzi N, Burden AD, Gach JE, Irvine AD, Kepiro L, Mockenhaupt M, Oon HH, Pinner J, Ranki A, Seyger MM, Soler-Palacin P, Storan ER, Tan ES, Valeyrie-Allanore L, Young HS, Trembath RC, Choon SE, Szell M, Bata-Csorgo Z, Smith CH, Di Meglio P, Barker JN, Capon F. AP1S3 mutations cause skin autoinflammation by disrupting keratinocyte autophagy and up-regulating IL-36 production. J Invest Dermatol. 2016;136(11):2251–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Berki DM, Liu L, Choon SE, David Burden A, Griffiths CE, Navarini AA, Tan ES, Irvine AD, Ranki A, Ogo T, Petrof G, Mahil SK, Duckworth M, Allen MH, Vito P, Trembath RC, McGrath J, Smith CH, Capon F, Barker JN. Activating CARD14 mutations are associated with generalized pustular psoriasis but rarely account for familial recurrence in psoriasis vulgaris. J Invest Dermatol. 2015;135(12):2964–70.PubMedCrossRefGoogle Scholar
  14. 14.
    Jordan CT, Cao L, Roberson ED, Pierson KC, Yang CF, Joyce CE, Ryan C, Duan S, Helms CA, Liu Y, Chen Y, McBride AA, Hwu WL, Wu JY, Chen YT, Menter A, Goldbach-Mansky R, Lowes MA, Bowcock AM. PSORS2 is due to mutations in CARD14. Am J Hum Genet. 2012;90(5):784–95.PubMedCrossRefGoogle Scholar
  15. 15.
    Ammar M, Bouchlaka-Souissi C, Helms CA, Zaraa I, Jordan CT, Anbunathan H, Bouhaha R, Kouidhi S, Doss N, Dhaoui R, Ben Osman A, Ben Ammar El Gaied A, Marrakchi R, Mokni M, Bowcock AM. Genome-wide linkage scan for psoriasis susceptibility loci in multiplex Tunisian families. Br J Dermatol. 2013;168(3):583–7.Google Scholar
  16. 16.
    Li M, Han J, Lu Z, Li H, Zhu K, Cheng R, Jiao Q, Zhang C, Zhu C, Zhuang Y, Wang Y, Shi J, Guo Y, Wu R, Yao Z. Prevalent and rare mutations in IL-36RN gene in chinese patients with generalized pustular psoriasis and psoriasis vulgaris. J Invest Dermatol. 2013;133(11):2637–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Mossner R, Frambach Y, Wilsmann-Theis D, Lohr S, Jacobi A, Weyergraf A, Muller M, Philipp S, Renner R, Traupe H, Burkhardt H, Kingo K, Koks S, Uebe S, Sticherling M, Sticht H, Oji V, Huffmeier U. 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.PubMedCrossRefGoogle Scholar
  18. 18.
    Setta-Kaffetzi N, Navarini AA, Patel VM, Pullabhatla V, Pink AE, Choon SE, Allen MA, Burden AD, Griffiths CE, Seyger MM, Kirby B, Trembath RC, Simpson MA, Smith CH, Capon F, Barker JN. Rare pathogenic variants in IL36RN underlie a spectrum of psoriasis-associated pustular phenotypes. J Invest Dermatol. 2013;133:1366–9. jid2012490 [pii].PubMedCrossRefGoogle Scholar
  19. 19.
    Wang TS, Chiu HY, Hong JB, Chan CC, Lin SJ, Tsai TF. Correlation of IL36RN mutation with different clinical features of pustular psoriasis in Chinese patients. Arch Dermatol Res. 2016;308(1):55–63.PubMedCrossRefGoogle Scholar
  20. 20.
    Gabay C, Towne JE. Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions. J Leukocyte Biol. 2015;97(4):645–52.PubMedCrossRefGoogle Scholar
  21. 21.
    Johnston A, Xing X, Wolterink L, Barnes DH, Yin Z, Reingold L, Kahlenberg JM, Harms PW, Gudjonsson JE. IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis. J Allergy Clin Immunol. 2016;140(1):109–20.PubMedCrossRefGoogle Scholar
  22. 22.
    Lian LH, Milora KA, Manupipatpong KK, Jensen LE. The double-stranded RNA analogue polyinosinic-polycytidylic acid induces keratinocyte pyroptosis and release of IL-36gamma. J Invest Dermatol. 2012;132(5):1346–53.Google Scholar
  23. 23.
    Hagforsen E, Edvinsson M, Nordlind K, Michaelsson G. Expression of nicotinic receptors in the skin of patients with palmoplantar pustulosis. Br J Dermatol. 2002;146(3):383–91.PubMedCrossRefGoogle Scholar
  24. 24.
    von Zumbusch L. Psoriasis und pustuloses exanthem. Arch Dermatol Syphilol. 1910;99:335–46.CrossRefGoogle Scholar
  25. 25.
    Navarini AA, Burden AD, Capon F, Mrowietz U, Puig L, Koks S, Kingo K, Smith C, Barker JN, network E. European consensus statement on phenotypes of pustular psoriasis. J Eur Acad Dermatol Venereol. 2017;31(11):1792–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Baker H, Ryan TJ. Generalized pustular psoriasis. A clinical and epidemiological study of 104 cases. Br J Dermatol. 1968;80(12):771–93.PubMedCrossRefGoogle Scholar
  27. 27.
    Zelickson BD, Muller SA. Generalized pustular psoriasis. A review of 63 cases. Arch Dermatol. 1991;127(9):1339–45.PubMedCrossRefGoogle Scholar
  28. 28.
    Bjorksten B, Gustavson KH, Eriksson B, Lindholm A, Nordstrom S. Chronic recurrent multifocal osteomyelitis and pustulosis palmoplantaris. J Pediatr. 1978;93(2):227–31.PubMedCrossRefGoogle Scholar
  29. 29.
    Eriksson MO, Hagforsen E, Lundin IP, Michaelsson G. Palmoplantar pustulosis: a clinical and immunohistological study. Br J Dermatol. 1998;138(3):390–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Hallopeau F. Sur une asphyxie locale des extremities avec polydactylite suppurative chronique et poussées éphémères de dermatite pustuleuse disséminée et symétrique. Bull Soc Fr Dermatol Syph. 1890;1:39–45.Google Scholar
  31. 31.
    Yerushalmi J, Grunwald MH, Hallel-Halevy D, Avinoach I, Halevy S. Chronic pustular eruption of the thumbs. Diagnosis: acrodermatitis continua of Hallopeau (ACH). Arch Dermatol. 2000;136(7):925–30.Google Scholar
  32. 32.
    Kardaun SH, Kuiper H, Fidler V, Jonkman MF. The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. J Cutan Pathol. 2010;37(12):1220–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Robinson A, Van Voorhees AS, Hsu S, Korman NJ, Lebwohl MG, Bebo BF Jr, Kalb RE. Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2012;67(2):279–88.PubMedCrossRefGoogle Scholar
  34. 34.
    Raposo I, Torres T. Palmoplantar psoriasis and palmoplantar pustulosis: current treatment and future prospects. Am J Clin Dermatol. 2016;17(4):349–58.PubMedCrossRefGoogle Scholar
  35. 35.
    Amor KT, Ryan C, Menter A. The use of cyclosporine in dermatology: part I. J Am Acad Dermatol. 2010;63(6):925–46.;; quiz 928–947.PubMedCrossRefGoogle Scholar
  36. 36.
    Majumdar S, Aggarwal BB. Methotrexate suppresses NF-kappaB activation through inhibition of IkappaBalpha phosphorylation and degradation. J Immunol. 2001;167(5):2911–20.Google Scholar
  37. 37.
    Viguier M, Aubin F, Delaporte E, Pages C, Paul C, Beylot-Barry M, Goujon C, Rybojad M, Bachelez H, Groupe de Recherche sur le Psoriasis de la Societe Francaise de Dermatologie. Efficacy and safety of tumor necrosis factor inhibitors in acute generalized pustular psoriasis. Arch Dermatol. 2012;148(12):1423–5.PubMedCrossRefGoogle Scholar
  38. 38.
    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.PubMedCrossRefGoogle Scholar
  39. 39.
    Bohner A, Roenneberg S, Eyerich K, Eberlein B, Biedermann T. Acute generalized pustular psoriasis treated with the IL-17A antibody secukinumab. JAMA Dermatol. 2016;152(4):482–4.PubMedCrossRefGoogle Scholar
  40. 40.
    Buder V, Herberger K, Jacobi A, Augustin M, Radtke MA. Ustekinumab in the treatment of palmoplantar pustular psoriasis—a case series of nine patients. J Dtsch Dermatol Ges. 2016;14(11):1108–13.PubMedCrossRefGoogle Scholar
  41. 41.
    Imafuku S, Honma M, Okubo Y, Komine M, Ohtsuki M, Morita A, Seko N, Kawashima N, Ito S, Shima T, Nakagawa H. 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.PubMedCrossRefGoogle Scholar
  42. 42.
    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(7):825–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Tartar D, Bhutani T, Huynh M, Berger T, Koo J. Update on the immunological mechanism of action behind phototherapy. J Drugs Dermatol. 2014;13(5):564–8.Google Scholar
  44. 44.
    Shmidt E, Wetter DA, Ferguson SB, Pittelkow MR. Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-alpha inhibitors: the Mayo Clinic experience, 1998 to 2010. J Am Acad Dermatol. 2012;67(5):e179–85.PubMedCrossRefGoogle Scholar
  45. 45.
    Marsland AM, Chalmers RJ, Hollis S, Leonardi-Bee J, Griffiths CE. Interventions for chronic palmoplantar pustulosis. Cochrane Database Syst Rev. 2006;(1):CD001433.Google Scholar
  46. 46.
    Bissonnette R, Poulin Y, Bolduc C, Maari C, Provost N, Syrotuik J, Poulin-Costello CM, Nigen S. Etanercept in the treatment of palmoplantar pustulosis. J Drugs Dermatol. 2008;7(10):940–6.Google Scholar
  47. 47.
    Morales-Munera C, Vilarrasa E, Puig L. Efficacy of ustekinumab in refractory palmoplantar pustular psoriasis. Br J Dermatol. 2013;168(4):820–4.PubMedCrossRefGoogle Scholar
  48. 48.
    Bissonnette R, Nigen S, Langley RG, Lynde CW, Tan J, Fuentes-Duculan J, Krueger JG. 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(10):1298–305.PubMedCrossRefGoogle Scholar
  49. 49.
    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(5):1198–9.PubMedCrossRefGoogle Scholar
  50. 50.
    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(4):477–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Oumeish OY, Al-Fouzan AW. Miscellaneous diseases affected by pregnancy. Clin Dermatol. 2006;24(2):113–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Satveer K. Mahil
    • 1
    • 2
    • 3
  • Jonathan N. Barker
    • 1
    • 2
    • 3
  • Francesca Capon
    • 1
    Email author
  1. 1.Division of Genetics and Molecular MedicineKing’s College LondonLondonUK
  2. 2.St John’s Institute of Dermatology, Guy’s and St Thomas’ HospitalLondonUK
  3. 3.Guy’s HospitalLondonUK

Personalised recommendations