Clinical and genetic differences between pustular psoriasis subtypes

Sophie Twelves, Alshimaa Mostafa, Nick Dand, Elias Burri, Katalin Farkas, Rosemary Wilson, Hywel L. Cooper, Alan D. Irvine, Hazel H. Oon, Külli Kingo, Sulev Köks, Ulrich Mrowietz, Luis Puig, Nick Reynolds, Eugene Sern-Ting Tan, Adrian Tanew, Kaspar Torz, Hannes Trattner, Mark Valentine, Shyamal WahieRichard B. Warren, Andrew Wright, Zsuzsa Bata-Csörgő, Marta Szell, Christopher EM. Griffiths, A David Burden, Siew-Eng Choon, Catherine H. Smith, Jonathan N. Barker, Alexander A. Navarini, Francesca Capon

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The term pustular psoriasis indicates a group of severe skin disorders characterised by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris (PV), can have an acute systemic (generalised pustular psoriasis, GPP) or chronic localised presentation (palmoplantar pustulosis, PPP; acrodermatitis continua of Hallopeau, ACH). While mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations.ObjectiveWe sought to characterise clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort.MethodsWe ascertained a dataset of unprecedented size, including 863 unrelated patients (251 GPP, 560 PPP, 28 ACH, 24 multiple diagnoses). We undertook mutation screening in 473 cases.ResultsPV concurrence was lowest in PPP (15.8% vs. 54.4% in GPP and 46.2% in ACH, P<0.0005 for both), whereas mean age of onset was earliest in GPP (31.0 years vs. 43.7 in PPP and 51.8 in ACH, P<0.0001 for both). The percentage of females was higher in PPP (77.0%) than GPP (62.5%) (P=5.8x10-5). The same applied to the prevalence of smokers (79.8% vs 28.3%, P<10-15). While AP1S3 alleles had similar frequency (0.03-0.05) across disease subtypes, IL36RN mutations were less common in PPP (0.03) than GPP (0.19) and ACH (0.16) (P=1.9x10-14 and 0.002, respectively). Importantly, IL36RN disease alleles had a dose-dependent effect on age of onset, in all forms of pustular psoriasis (P=0.003).ConclusionsThe analysis of an unparalleled patient resource revealed key clinical and genetic differences between PPP and GPP.
Original languageEnglish
Pages (from-to)1021-1026
JournalJournal of Allergy and Clinical Immunology
Issue number3
Early online date21 Jul 2018
Publication statusPublished - 31 Jul 2018


  • Generalised pustular psoriasis
  • palmoplantar pustulosis
  • acrodermatitis continua of Hallopeau
  • genotype-phenotype correlation


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