期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 143, 期 3, 页码 1021-1026出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2018.06.038
关键词
Generalized pustular psoriasis; palmoplantar pustulosis; acrodermatitis continua of Hallopeau; IL36RN; AP1S3; genotype-phenotype correlation
资金
- Department of Health through the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and comprehensive Biomedical Research Centre
- King's College London
- King's College Hospital NHS Foundation Trust [guysbrc-2012-1]
- Medical Research Council (MRC) Stratified Medicine award [MR/L011808/1]
- Efficacy and Mechanism Evaluation (EME) Programme
- MRC
- NIHR [EME 13/50/17]
- Newcastle MRC/EPSRC Molecular Pathology Node
- King's Bioscience Institute
- Guy's and St Thomas' Charity Prize PhD Programme in Biomedical and Translational Science
- PPRC grant from the European Association of Dermatology and Venereology (EADV)
- National Institutes of Health Research (NIHR) [guysbrc-2012-1, EME/13/50/17] Funding Source: National Institutes of Health Research (NIHR)
- MRC [MR/N005872/1, MR/S003126/1, MR/L011808/1] Funding Source: UKRI
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 themean age of onset was earliest in GPP (31.0 vs 43.7 years in PPP and 51.8 years inACH, P<.0001 for both). The percentage of female patients was greater in PPP (77.0%) than in GPP (62.5%; P = 5.8 x 10(-5)). The same applied to the prevalence of smokers (79.8% vs 28.3%, P < 10(-1)5). 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) andACH(0.16; P51.9310 214 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据