Clinical and genetic differences between pustular psoriasis subtypes

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:143

Article

Twelves, Sophie¹  Mostafa, Alshimaa^2,3  Dand, Nick¹  Burri, Elias²  Wilson, Rosemary⁵  Cooper, Hywel L.⁶  Irvine, Alan D.⁷  Oon, Hazel H.⁸  Kingo, Kulli^9,10  Koks, Sulev¹¹  Mrowietz, Ulrich¹²  Puig, Luis¹³  Reynolds, Nick^14,15  Tan, Eugene Sern-Ting⁸  Tanew, Adrian¹⁶  Torz, Kaspar¹²  Trattner, Hannes¹⁶  Valentine, Mark¹⁷  Wahie, Shyamal^18,19  Warren, Richard B.^20,21  Wright, Andrew^22,23  Bata-Csorgo, Zsuzsa^24,25  Szell, Marta^24,4  Griffiths, Christopher E. M.^20,21  Burden, A. David²⁶  Choon, Siew-Eng²⁷  Smith, Catherine H.⁵  Barker, Jonathan N.⁵  Navarini, Alexander A.²  Capon, Francesca¹ 

[1] Kings Coll London, Sch Basic & Med Biosci, Dept Med & Mol Genet, London, England

[2] Univ Hosp Zurich, Dept Dermatol, Zurich, Switzerland

[3] Beni Suef Univ, Dept Dermatol, Bani Suwayf, Egypt

[4] Univ Szeged, Dept Med Genet, Szeged, Hungary

[5] Kings Coll London, St Johns Inst Dermatol, Sch Basic & Med Biosci, London, England

[6] Portsmouth Hosp Trust, Portsmouth Dermatol Unit, Portsmouth, Hants, England

[7] Trinity Coll Dublin, Our Ladys Childrens Hosp Crumlin & Clin Med, Paediat Dermatol, Dublin, Ireland

[8] Natl Skin Ctr, Dept Dermatol, Singapore, Singapore

[9] Univ Tartu, Dept Dermatol, Tartu, Estonia

[10] Tartu Univ Hosp, Clin Dermatol, Tartu, Estonia

[11] Univ Tartu, Dept Pathophysiol, Tartu, Estonia

[12] Univ Med Ctr, Dept Dermatol, Psoriasis Ctr, Campus Kiel, Schleswig Holstein, Germany

[13] Hosp Santa Creu & Sant Pau, Dept Dermatol, Barcelona, Spain

[14] Newcastle Univ, Inst Cellular Med, Med Sch, Newcastle Upon Tyne, Tyne & Wear, England

[15] Newcastle Hosp NHS Fdn Trust, Royal Victoria Infirm, Dept Dermatol, Newcastle Upon Tyne, Tyne & Wear, England

[16] Med Univ Vienna, Dept Dermatol, Vienna, Austria

[17] Univ Washington, Div Dermatol, Sch Med, Seattle, WA 98195 USA

[18] Univ Hosp North Durham, Durham, England

[19] Darlington Mem Hosp, Darlington, Durham, England

[20] Univ Manchester, Dermatol Ctr, Salford Royal Hosp, Manchester, Lancs, England

[21] Acad Hlth Sci Ctr, Manchester, Lancs, England

[22] St Lukes Hosp, Bradford, W Yorkshire, England

[23] Univ Bradford, Ctr Skin Sci, Bradford, W Yorkshire, England

[24] MTA SZTE Dermatol Res Grp, Szeged, Hungary

[25] Univ Szeged, Dept Dermatol & Allergol, Szeged, Hungary

[26] Univ Glasgow, Inst Infect Inflammat & Immun, Glasgow, Lanark, Scotland

[27] Monash Univ Malaysia, Jeffrey Cheah Sch Med & Hlth Sci, Hosp Sultanah Aminah, Dept Dermatol, Johor Baharu, Malaysia

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

DOI  :  10.1016/j.jaci.2018.06.038

来源: Elsevier

【 摘 要 】

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.

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