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. 2019 Mar;143(3):1021-1026.
doi: 10.1016/j.jaci.2018.06.038. Epub 2018 Jul 21.

Clinical and genetic differences between pustular psoriasis subtypes

Sophie Twelves  1 , Alshimaa Mostafa  2 , Nick Dand  1 , Elias Burri  3 , Katalin Farkas  4 , Rosemary Wilson  5 , Hywel L Cooper  6 , Alan D Irvine  7 , Hazel H Oon  8 , Külli Kingo  9 , Sulev Köks  10 , Ulrich Mrowietz  11 , Luis Puig  12 , Nick Reynolds  13 , Eugene Sern-Ting Tan  8 , Adrian Tanew  14 , Kaspar Torz  11 , Hannes Trattner  14 , Mark Valentine  15 , Shyamal Wahie  16 , Richard B Warren  17 , Andrew Wright  18 , Zsuzsa Bata-Csörgő  19 , Marta Szell  20 , Christopher E M Griffiths  17 , A David Burden  21 , Siew-Eng Choon  22 , Catherine H Smith  5 , Jonathan N Barker  23 , Alexander A Navarini  3 , Francesca Capon  1
Affiliations

Clinical and genetic differences between pustular psoriasis subtypes

Sophie Twelves et al. J Allergy Clin Immunol. 2019 Mar.

Abstract

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.

Keywords: AP1S3; Generalized pustular psoriasis; IL36RN; acrodermatitis continua of Hallopeau; genotype-phenotype correlation; palmoplantar pustulosis.

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Figures

None
Graphical abstract
Fig 1
Fig 1
Features of pustular psoriasis observed in the disease cohort. A, Mean age of onset was compared across disease groups by using a Kruskal-Wallis test followed by the Dunn multiple comparison test. B, Differences in PV concurrence were analyzed with a χ2 test. C, Differences in the proportion of affected female subjects were assessed by using a χ2 test. The dashed line indicates the percentage of female subjects in the general population. D, Differences in combined frequency of IL36RN mutations were assessed across ethnic groups by using a χ2 test. Pairwise comparisons were undertaken with the Fisher exact test. The analysis was restricted to patients with GPP because this is the only group for which data were available for multiple ethnicities. Other mutations indicates alleles seen only once in the cohort. The notation c.115+6T>C; p.Pro76Leu refers to patients carrying the 2 variants on the same haplotype. E, Effects of IL36RN mutations on age of onset were assessed by using linear regression. **P < .01, ***P < .001, and ****P < .0001.
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