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Twelves, Sophie; Mostafa, Alshimaa; Dand, Nick; Burri, Elias; Farkas, Katalin; Wilson, Rosemary; Cooper, Hywel L.; Irvine, Alan D.; Oon, Hazel H.; Kingo, Külli; Köks, Sulev; Mrowietz, Ulrich; Puig, Luis; Reynolds, Nick; Tan, Eugene Sern-Ting; Tanew, Adrian; Torz, Kaspar; Trattner, Hannes; Valentine, Mark; Wahie, Shyamal; Warren, Richard B.; Wright, Andrew; Bata-Csörgő, Zsuzsa; Szell, Marta; Griffiths, Christopher E.M.; Burden, A. David; Choon, Siew-Eng; Smith, Catherine H.; Barker, Jonathan N.; Navarini, Alexander A.; Capon, Francesca
Journal of allergy and clinical immunology, March 2019, 2019-03-00, 20190301, Letnik: 143, Številka: 3Journal Article
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. We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort. 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. 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). The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP. Display omitted
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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