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 Wahie; Richard 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

doi:10.1016/j.jaci.2018.06.038

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

Division of Musculoskeletal & Dermatological Sciences (L5)

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1021-1026
Number of pages	6
Journal	The Journal of allergy and clinical immunology
Volume	143
Issue number	3
Early online date	21 Jul 2018
DOIs	https://doi.org/10.1016/j.jaci.2018.06.038
Publication status	Published - 21 Jul 2018

Keywords

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

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Twelves, S., Mostafa, A., Dand, N., Burri, E., Farkas, K., Wilson, R., Cooper, H. L., Irvine, A. D., Oon, H. H., Kingo, K., Köks, S., Mrowietz, U., Puig, L., Reynolds, N., Tan, E. S.-T., Tanew, A., Torz, K., Trattner, H., Valentine, M., ... Capon, F. (2018). Clinical and genetic differences between pustular psoriasis subtypes. The Journal of allergy and clinical immunology, 143(3), 1021-1026. https://doi.org/10.1016/j.jaci.2018.06.038

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title = "Clinical and genetic differences between pustular psoriasis subtypes",

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",

author = "Sophie Twelves and Alshimaa Mostafa and Nick Dand and Elias Burri and Katalin Farkas and Rosemary Wilson and Cooper, {Hywel L} and Irvine, {Alan D} and Oon, {Hazel H} and K{\"u}lli Kingo and Sulev K{\"o}ks and Ulrich Mrowietz and Luis Puig and Nick Reynolds and Tan, {Eugene Sern-Ting} and Adrian Tanew and Kaspar Torz and Hannes Trattner and Mark Valentine and Shyamal Wahie and Warren, {Richard B} and Andrew Wright and Zsuzsa Bata-Cs{\"o}rg{\H o} and Marta Szell and Griffiths, {Christopher E M} and Burden, {A David} and Siew-Eng Choon and Smith, {Catherine H} and Barker, {Jonathan N} and Navarini, {Alexander A} and Francesca Capon",

year = "2018",

month = jul,

day = "21",

doi = "10.1016/j.jaci.2018.06.038",

language = "English",

volume = "143",

pages = "1021--1026",

journal = "The Journal of allergy and clinical immunology",

issn = "0091-6749",

publisher = "Elsevier BV",

number = "3",

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Twelves, S, Mostafa, A, Dand, N, Burri, E, Farkas, K, Wilson, R, Cooper, HL, Irvine, AD, Oon, HH, Kingo, K, Köks, S, Mrowietz, U, Puig, L, Reynolds, N, Tan, ES-T, Tanew, A, Torz, K, Trattner, H, Valentine, M, Wahie, S, Warren, RB, Wright, A, Bata-Csörgő, Z, Szell, M, Griffiths, CEM, Burden, AD, Choon, S-E, Smith, CH, Barker, JN, Navarini, AA & Capon, F 2018, 'Clinical and genetic differences between pustular psoriasis subtypes', The Journal of allergy and clinical immunology, vol. 143, no. 3, pp. 1021-1026. https://doi.org/10.1016/j.jaci.2018.06.038

TY - JOUR

T1 - Clinical and genetic differences between pustular psoriasis subtypes

AU - Twelves, Sophie

AU - Mostafa, Alshimaa

AU - Dand, Nick

AU - Burri, Elias

AU - Farkas, Katalin

AU - Wilson, Rosemary

AU - Cooper, Hywel L

AU - Irvine, Alan D

AU - Oon, Hazel H

AU - Kingo, Külli

AU - Köks, Sulev

AU - Mrowietz, Ulrich

AU - Puig, Luis

AU - Reynolds, Nick

AU - Tan, Eugene Sern-Ting

AU - Tanew, Adrian

AU - Torz, Kaspar

AU - Trattner, Hannes

AU - Valentine, Mark

AU - Wahie, Shyamal

AU - Warren, Richard B

AU - Wright, Andrew

AU - Bata-Csörgő, Zsuzsa

AU - Szell, Marta

AU - Griffiths, Christopher E M

AU - Burden, A David

AU - Choon, Siew-Eng

AU - Smith, Catherine H

AU - Barker, Jonathan N

AU - Navarini, Alexander A

AU - Capon, Francesca

PY - 2018/7/21

Y1 - 2018/7/21

N2 - 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.

AB - 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.

KW - AP1S3

KW - Generalized pustular psoriasis

KW - IL36RN

KW - acrodermatitis continua of Hallopeau

KW - genotype-phenotype correlation

KW - palmoplantar pustulosis

U2 - 10.1016/j.jaci.2018.06.038

DO - 10.1016/j.jaci.2018.06.038

M3 - Article

C2 - 30036598

SN - 0091-6749

VL - 143

SP - 1021

EP - 1026

JO - The Journal of allergy and clinical immunology

JF - The Journal of allergy and clinical immunology

IS - 3

ER -

Clinical and genetic differences between pustular psoriasis subtypes

Abstract

Keywords

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