317 Features of pustular psoriasis observed in 863 patients: Clinical and genetic analysis of a multi-ethnic cohort

      Pustular psoriasis is a rare autoinflammatory skin disease characterised by the appearance of small sterile pustules on inflamed skin. The disease can be classified into three sub-types. Generalised pustular psoriasis (GPP) is an acute condition with widespread pustulation. Acrodermatitis continua of Hallopeau (ACH) and palmoplantar pustular psoriasis (PPP) are chronic and localised diseases affecting the nail apparatus (ACH), or the palms and/or soles. Mutations in IL36RN and AP1S3 have been associated with a proportion of pustular psoriasis cases, but the rarity of the disease has hindered attempts to study correlations between genotype and phenotype. We analysed disease presentation in 863 patients, with 459 of these cases additionally screened for mutations in IL36RN and AP1S3. The mean age of onset was earliest in GPP (P<0.0001), whereas plaque psoriasis concurrence was lowest in PPP (P<0.0005). IL36RN disease mutations had similar prevalence in GPP and ACH, but were significantly less common in PPP (P<0.002). We identified a dose-dependent association between IL36RN disease alleles and early age of onset (P=0.004) in all disease sub-types. AP1S3 mutations had similar frequency in all disease forms, but occurred almost exclusively in females (23:1, F:M). This represents the largest pustular psoriasis cohort examined to date. The results highlight the importance of examining extended clinical resources and lay the foundation for patient stratification and personalised treatment based on IL36RN deficiency.