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 E M Griffiths, A David Burden, Siew-Eng Choon, Catherine H Smith, Jonathan N Barker, Alexander A Navarini, Francesca Capon

Research output: Contribution to journalArticlepeer-review


BACKGROUND: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations.

OBJECTIVE: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort.

METHODS: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases.

RESULTS: Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P < .0005 for both), whereas the mean age of onset was earliest in GPP (31.0 vs 43.7 years in PPP and 51.8 years in ACH, P < .0001 for both). The percentage of female patients was greater in PPP (77.0%) than in GPP (62.5%; P = 5.8 × 10-5). The same applied to the prevalence of smokers (79.8% vs 28.3%, P < 10-15). Although AP1S3 alleles had similar frequency (0.03-0.05) across disease subtypes, IL36RN mutations were less common in patients with PPP (0.03) than in those with GPP (0.19) and ACH (0.16; P = 1.9 × 10-14 and .002, respectively). Importantly, IL36RN disease alleles had a dose-dependent effect on age of onset in all forms of pustular psoriasis (P = .003).

CONCLUSIONS: The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP.

Original languageEnglish
Pages (from-to)1021-1026
Number of pages6
JournalThe Journal of allergy and clinical immunology
Issue number3
Early online date21 Jul 2018
Publication statusPublished - 21 Jul 2018


  • AP1S3
  • Generalized pustular psoriasis
  • IL36RN
  • acrodermatitis continua of Hallopeau
  • genotype-phenotype correlation
  • palmoplantar pustulosis


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