Clinical and genetic differences between pustular psoriasis subtypes

Twelves, S. et al. (2019) Clinical and genetic differences between pustular psoriasis subtypes. Journal of Allergy and Clinical Immunology, 143(3), pp. 1021-1026. (doi: 10.1016/j.jaci.2018.06.038) (PMID:30036598) (PMCID:PMC6403101)

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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.

Item Type:Articles
Additional Information:Supported by the Department of Health through the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and comprehensive Biomedical Research Centre awards to Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust (guysbrc-2012-1) and to the NIHR-Newcastle Biomedical Research Centre. This work was funded by a Medical Research Council (MRC) Stratified Medicine award (MR/L011808/1; to J.N.B., F.C., and C.H.S.) and by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership (grant EME 13/50/17 to C.H.S., F.C., J.N.B., C.E.M.G., and N.R.). N.R. is also supported by the Newcastle MRC/EPSRC Molecular Pathology Node. S.T. is supported by the King's Bioscience Institute and the Guy's and St Thomas' Charity Prize PhD Programme in Biomedical and Translational Science. The European Rare and Severe Psoriasis Expert Network is funded by a PPRC grant from the European Association of Dermatology and Venereology (EADV; to A.A.N. and J.N.B.).
Keywords:AP1S3, generalised pustular psoriasis, IL36RN, acrodermatitis continua of Hallopeau, genotype-phenotype correlation, palmoplantar pustulosis.
Glasgow Author(s) Enlighten ID:Burden, Professor David
Authors: 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., Sern-Ting Tan, E., Tanew, A., Torz, K., Trattner, H., Valentine, M., Wahie, S., Warren, R. B., Wright, A., Bata-Csörgő, Z., Szell, M., Griffiths, C. E., Burden, A. D., Choon, S.-E., Smith, C. H., Barker, J. N., Navarini, A. A., and Capon, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Allergy and Clinical Immunology
ISSN (Online):1097-6825
Published Online:01 July 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Journal of Allergy and Clinical Immunology 143(3): 1021-1026
Publisher Policy:Reproduced under a Creative Commons License

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