# Pustular Psoriasis and Acute Generalized
## 6 Treatment  
Traditionally, PP is treated with oral retinoids like acitretin and topical corticosteroids [4]. Additional agents that are used include cyclosporine, methotrexate, corticosteroids, TNF-alpha inhibitors, and more recently, IL-17 inhibitors [3,4]. Although PP typically requires systemic therapy, topical agents such as calcipotriene and corticosteroids are favored as first-line treatments in the localized forms of PP, most often ACH [3,4]. Recent advancements in the understanding of disease pathogenesis have led to new therapeutic approaches that can be tailored to specific mediators of the pathologic pathways. However, the lower prevalence of PP has limited the data on its treatment in comparison to the multitude of targeted biologic therapeutics for PV [3]. Specifically, anti-IL36 receptor monoclonal antibodies are currently under development for the treatment of PP [3,9]. In a study by [PERSON] et al., these monoclonal antibodies showed promising results in seven patients with GPP. The patients were followed weekly, and the severity of their lesions was rated based on the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA), with a score of 0 corresponding to clear skin. By week four, all seven patients received a score of 0. Of note, four of these seven patients did not have a mutation in the IL36 RN gene, suggesting that IL-36 plays a role in PP pathogenesis regardless of the presence of mutational status [9]. Traditional biologic therapy for PV can also be applied to PP. For example, adailimumab, a TNF-alpha inhibitor, has shown efficacy in the treatment of GPP and PPPP in small numbers of patients [35, 36, 37, 38]. Similarly, upstreamukinumab, an anti-IL-12/23 monoclonal antibody, has shown efficacy in treating recalcitrant GPP [39]. Anti-sporiatic drugs targeting the IL-17 pathway (secukinumab, izekizumab, and broadumab) have all shown positive results as potential alternative treatments for PP, although data remains limited with most studies restricted to the Japanese population [40, 41, 42]. For example, an open-label study showed that 10 out of 12 adults with GPP showed clinical global impression ratings of \"much improved\" or \"very much improved\" at week 16, with the initiation of secukinumab [40]. Interestingly, there are case reports of paradoxical flarings of PP attributed to the use of TNF-alpha, IL-12/23, and IL-17 inhibitors [43, 44, 45], necessitating cessation of the implicated drug and initiation of alternative treatments like cyclosporine. The newest biologic treatments developed for PV target IL-23, including guselkumab, risankizumab, and tildrakizumab. Similar to other biologics, their use has been extrapolated to the treatment of PP. For example, guselkumab has demonstrated promising results for patients with PPPP and GPP [7]. Guselkumab was shown to be efficacious in a phase III RCT in Japanese patients with PPPP [7]. The Palmoplantar Psoriasis Area and Severity Index (PPPASI) was used to evaluate patient response to guselkumab and 52. Fifty-seven percent of patients saw at least a 50% improvement in total PPPASI score (PPPASI-50) at week 16 [7]. Ten Japanese patients with GPP were enrolled in a phase III, open-label study that evaluated the efficacy and safety of guselkumab [11]. At week 16, seven of the nine remaining patients had achieved treatment success, defined as a Clinical Global Impression score of \"very much improved\", \"much improved\", or \"minimally improved\" [11]. Other potentially therapeutic targets include IL-1\(\beta\) and the IL-1 receptor. Two monoclonal antibodies have been designed to bind to IL-1\(\beta\): gevokizumab and canakinumab. Two patients with severe GPP who received gevokizumab as part of an open-label, expanded-access study \"had a respective 79% and 65% reduction in GPP area and severity index scores at weeks 4 and 12\" [12]. Canakinumab therapy has been reported to significantly improve the lesions of a patient with GPP who previously failed therapy with anakinra [13].