## 1 Introduction  
Generalized pustular psoriasis (GPP) is defined as primary, sterile, macroscopically visible pustules on non-acral skin (excluding cases where pustulation is restricted to psoriatic plaques) [1; 2; 3; 4]. GPP can occur with or without systemic inflammation, with or without plaque psoriasis, and can be either a relapsing (>1 episode) or persistent (>3 months) condition [5]. There is a large degree of variability in the prevalence of GPP in the published literature, particularly between Western and Asian countries, reflecting different methodologies, populations, and definitions of GPP, and the inclusion, or lack of differentiation from localized variants of pustular psoriasis. The point prevalence, annual prevalence and annual incidence of GPP was estimated in Sweden at 9.1 per 100,000, 1.5 per 100,000, and 1.53 per 100,000, respectively [6]. A national French questionnaire-based study estimated an annual prevalence of GPP at 0.18 cases per 100,000 [7]. A review of a national insurance claims database in the Republic of Korea reported a prevalence of 12 cases per 100,000 persons [8]. Another Japanese survey of 575 community center hospitals found a prevalence of 0.74 patients per 100,000 persons [9].  
GPP has been observed in 9% of incident pustular psoriasis patients, being much rarer than palmoplantar pustulosis (PPP) that occurs in 83% of cases [10]. GPP results from dysregulation of the innate immune system, particularly involving the interleukin (IL)-36 inflammatory pathway, induction of inflammatory keratinocyte responses, and recruitment of neutrophils [11]. Mutations in IL36 RN, CARD13, AP1S3, MPO, TNIPL, SERPINA3, and SERPINA1 have been shown to be associated with GPP, among which loss-of-function mutation in IL36 RN is the dominant mutation with the highest prevalence. IL-36 RN, MPO, and SERPINA 1/3 mutations lead to the upregulation of IL-36 signalling, which further activates the downstream proinflammatory NF-kB and MAPK pathways. AP1S3 and TNIP1 loss-of-function mutations and CARD14 gain-of-function mutations are involved in IL-36 signalling by hyperactivating the NF-kB pathway. The upregulated IL-36 signalling promotes the proliferation of IL-17-producing CD4+Th17 cells, and these cytokines secreted by infiltrating CD4+T cells further propagate these inflammatory cycles by inducing expression of IL-36 and other inflammatory mediators. The interaction of the IL-36 pathway and the IL-23/IL-17 axis underlies the immunological disturbances of GPP, indicating that innate and adaptive immune responses intertwine in the pathogenesis of GPP [12].  
GPP flares are acute events, which can be very impactful and occasionally associated with mortality due to complications, including sepsis, acute respiratory distress syndrome, renal failure, and congestive heart failure [13]. Various triggers, such as corticosteroids withdrawal, drugs, stressful life events, and infections, have been reported [13]. Given the rarity of the disease in Europe compared to Japan and Asian countries [6; 7; 8; 9; 14; 15], the clinical characteristics of patients experiencing a flare of GPP are hardly reported. The aim of this study was to investigate the clinical characteristics of a series of patients experiencing a flare of GPP in a real-life multicenter setting.