Format

Send to

Choose Destination
J Allergy Clin Immunol. 2018 Jul 21. pii: S0091-6749(18)31039-X. doi: 10.1016/j.jaci.2018.06.038. [Epub ahead of print]

Clinical and genetic differences between pustular psoriasis subtypes.

Author information

1
Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, United Kingdom.
2
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Department of Dermatology, Beni Suef University, Beni Suef, Egypt.
3
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
4
Department of Medical Genetics, University of Szeged, Szeged, Hungary.
5
St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, United Kingdom.
6
Portsmouth Dermatology Unit, Portsmouth Hospitals Trust, Portsmouth, United Kingdom.
7
Paediatric Dermatology, Our Lady's Children's Hospital Crumlin, and Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
8
Department of Dermatology, National Skin Centre, Singapore.
9
Department of Dermatology, University of Tartu, and the Clinic of Dermatology, Tartu University Hospital, Tartu, Estonia.
10
Department of Pathophysiology, University of Tartu, Tartu, Estonia.
11
Psoriasis Center at the Department of Dermatology, University Medical Center, Schleswig-Holstein, Campus Kiel, Kiel, Germany.
12
Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
13
Institute of Cellular Medicine, Medical School, Newcastle University and the Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
14
Department of Dermatology, Medical University of Vienna, Vienna, Austria.
15
Division of Dermatology, University of Washington School of Medicine, Seattle, Wash.
16
University Hospital of North Durham and Darlington Memorial Hospital, Darlington, United Kingdom.
17
Dermatology Centre, Salford Royal Hospital, University of Manchester and the Academic Health Science Centre, Manchester, United Kingdom.
18
St Lukes Hospital, Bradford, and the Centre for Skin Science, University of Bradford, Bradford, United Kingdom.
19
MTA-SZTE Dermatological Research Group, Szeged, and the Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
20
MTA-SZTE Dermatological Research Group, Szeged, and the Department of Medical Genetics, University of Szeged, Szeged, Hungary.
21
Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, United Kingdom.
22
Department of Dermatology, Hospital Sultanah Aminah, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Johor Bahru, Selangor, Malaysia.
23
St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, United Kingdom. Electronic address: jonathan.barker@kcl.ac.uk.

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

PMID:
30036598
DOI:
10.1016/j.jaci.2018.06.038
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center