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Introduction: Data on generalized pustular psoriasis (GPP) in Poland are limited. Therefore, this study aimed to evaluate the demographic and clinical characteristics of Polish patients with GPP. In addition, the effect of the frequency of disease flares and the concomitant presence of psoriasis vulgaris (PV) on patient characteristics was evaluated. Methods: In this retrospective study, medical records of patients hospitalized for GPP in dermatology departments of the Polish Generalized Pustular Psoriasis Group were analyzed. Results: A total of 90 patients from 14 dermatology centers were included. The median age of patients was 59 (range, 5–85) years, and most patients were female (68.9%). The most common comorbidity was hypertension (43.3%), followed by cardiovascular diseases, diabetes, and hyperlipidemia. The median duration of GPP was 3 years, and the median number of flares was 2. Hospitalization was required in 67% of flares. The main triggering factors were drugs (20.5%) and infections (19.3%). Women and men with GPP differed in terms of age (p < 0.01), distribution of comorbidities, and selected triggering factors (stress: p < 0.05). Almost 25% of patients experienced more than one flare per year. Patients with different frequency of flares did not differ significantly in age, sex distribution, or comorbidities, but those with a higher frequency of flares had a shorter disease duration (median: 0.6 vs. 4.0 years; p < 0.01). In 59.1% of patients, GPP was accompanied by PV. Patients with GPP and PV were younger than those with GPP alone (median: 48.0 vs. 66.0 years; p < 0.01). Conclusions: In this study, the general demographic and clinical characteristics of patients with GPP were consistent with those described in other studies. However, a high rate of flares requiring hospitalization and a significant percentage of patients experiencing more than one flare per year indicate the unmet need in the management of patients with GPP. [ABSTRACT FROM AUTHOR]

Objectives: Generalized pustular psoriasis (GPP) is a rare, life-threatening skin inflammatory disorder. This study aimed to describe the disease course, treatment strategies, and healthcare utilization among patients with GPP in Portugal. Methods: This multicentric, observational, retrospective study included consecutive adult patients with GPP undergoing a dermatology evaluation in different reporting institutions by experienced dermatologists between 2002 and 2023. Results: A total of 59 patients were assessed. Most of the cohort had a previous history of plaque psoriasis (71%) and 83% presented at least one comorbidity. At the initial encounter, 64% of the cohort needed hospitalization. Systemic involvement was common, including fever (37%), and elevated white blood cell count and erythrocyte sedimentation rate/C-reactive protein (49%). Nearly, 73% of patients initiated systemic drugs, and 70% had to discontinue the first treatment. During the study, 98% of patients experienced at least one flare. At the last visit, 3.4% of patients had died, and 71.2% exhibited signs of active disease despite undergoing treatment. Conclusions: Our study demonstrates that GPP is a chronic, debilitating condition associated with systemic involvement, frequent flares, and hospitalizations, despite receiving multiple systemic treatments. Improved disease awareness and new treatments are needed to improve patient care and decrease the burden of the disease. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare, chronic, heterogeneous, and potentially life‐threatening disease characterized by primary, sterile, and macroscopically visible pustules with or without systemic symptoms. There are ethnic differences in the genetic mutations associated with GPP that might affect the clinical manifestations and treatment responses. Currently, there is limited evidence from the patient population in the Asia‐Pacific (APAC) region, resulting in a general paucity of information on the effective management of patients with GPP in this region. This modified Delphi panel study aimed to identify current evidence and gain advanced insights to facilitate the development of a regionally tailored APAC consensus on the management of GPP. A systematic literature review (SLR) was conducted to identify published literature and develop consensus statements on (i) definition and clinical course, (ii) diagnosis of GPP, (iii) treatment outcomes, goals, and monitoring measures, and (iv) optimal management strategies and clinical practices. Statements were rated by a panel of dermatologists in two rounds, with the threshold for consensus at ≥80% agreement. Twenty experts from the APAC region reached consensus on 106 statements that were developed based on the SLR and experts' collective expertise. The experts agreed that GPP is a rare, severe, and potentially life‐threatening condition that is distinct from plaque psoriasis. This consensus emphasized the importance of a tailored treatment strategy taking into account the GPP flare severity and each patient's unique clinical circumstances. The experts reached consensus on the severity classification of GPP flares and recommended first‐line and maintenance treatment options for adult GPP, childhood GPP, and GPP in pregnancy. These consensus outcomes have been synthesized into treatment algorithms to guide dermatologists in the APAC region in their clinical decision‐making processes. [ABSTRACT FROM AUTHOR]

Background: Real-world data on health-related quality of life (HRQoL) in generalized pustular psoriasis (GPP) are scarce and studies have been restricted in terms of instruments used for assessments. Objective: To assess generic and dermatology-specific HRQoL of patients with GPP compared with patients with plaque psoriasis using real-world data from the Swedish National Register for Systemic Treatment of Psoriasis. Methods: Cross-sectional data from 2006 to 2021 including 7041 individuals with plaque psoriasis without GPP and 80 patients with GPP, of which 19% also had plaque psoriasis. Total scores for the EuroQol-5 Dimensions (EQ-5D) and Dermatology Life Quality Index (DLQI), as well as degree of severity within the instruments' dimensions/questions, were compared between patient groups. Results: EQ-5D scores were significantly (p < .01) lower (worse) in patients with GPP (mean [standard deviation (SD)] 0.613 [0.346]) vs. patients with plaque psoriasis (mean [SD] 0.715 [0.274]), indicating lower generic HRQoL of patients with GPP. Significantly (p < .01) higher (worse) total DLQI scores were observed for patients with GPP (mean [SD] 10.6 [8.9]) compared with patients with plaque psoriasis (mean [SD] 7.7 [7.1]), with proportionally more patients with GPP having severe (20% vs. 16%) and very severe (17% vs. 8%) problems. The worsened scores for GPP vs. plaque psoriasis were consistent across EQ-5D dimensions and DLQI questions. Conclusions: Individuals with GPP have a considerable impairment in both generic and dermatology-specific HRQoL. The HRQoL was significantly worse in individuals with GPP compared to individuals with plaque psoriasis. The significant HRQoL impairment of GPP shows the potential value of better healthcare interventions for this multisystem disease. [ABSTRACT FROM AUTHOR]

Background: Generalized pustular psoriasis (GPP) is a rare, potentially life‐threatening skin disease often requiring long‐term therapy. We aimed to evaluate the use of Interleukin (IL)‐17A inhibitors (secukinumab and ixekizumab) in GPP patients over 96 weeks. Methods: We retrospectively analyzed a case series of 18 patients with GPP who received secukinumab (n = 13) and ixekizumab (n = 5) therapy with a 96‐week follow‐up period. The primary effectiveness analysis included determining the percentage of patients who achieved ≥90% or 100% improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score. Adherence was captured using the medication possession ratio (MPR). Results: Using the as‐observed (AO) method, 87% and 67% of patients treated with secukinumab or ixekizumab achieved GPPASI 90 and 100 responses, respectively. At Week 96, the mean GPPASI improvements from baseline GPPASI were 96.3% (95% CI: 0.91–1.01) using the AO method. After Week 48, 14 patients tapered (n = 8) or terminated (n = 6) the treatment. High‐adherence therapy (MPR ≥ 80%) was significantly superior to the low‐adherence group in the rate of patients achieving a GPPASI 100 response (AO, 100% vs. 38%, P < 0.05). By Week 96, 5 (27.8%) patients had new GPP flares, and 4 (80%) were in the low‐adherence group. No new safety signals occurred. Conclusion: IL‐17A inhibitors led to effective and sustained improvement in GPP patients, and high‐adherence therapy had long‐term positive effects on skin clearance. Given its relapsing nature, improving compliance is beneficial for long‐term clinical management. [ABSTRACT FROM AUTHOR]

Background: Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory cutaneous disease. IL-36 is a key treatment target in GPP. Spesolimab, a humanized monoclonal antibody of the IL-36 receptor, has demonstrated a good efficacy and a favorable safety profile in adults with GPP. However, data on its use in children are scarce. Methods: We treated patients aged 4– 12 years with GPP with a single dose of spesolimab. The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score, GPPGA pustulation sub-score, Generalized Pustular Psoriasis Area and Severity Index (GPPASI), and the Japanese Dermatological Association severity index for GPP were evaluated. The levels of IL-36α, IL-36β, and IL-36γ were detected by the magnetic bead-based immunoassays, and the levels of IL-17A, IL-17C, IFN-γ, TNF, IL-6, and IL-8 were measured by the Olink proximity extension assay technology. Results: We included five patients (four boys and one girl) with a median age was 6.9 years old (range: 4.8 to 10.6 years), and a median age of onset of 1.7 years (range: 3 months– 10 years and 5 months). After 1 week of spesolimab administration, all patients had a total GPPGA score of 0/1 and pustulation subscore of 0, all patients had a GPPASI of 50, and four patients had a GPPASI of 75. Meanwhile, plasma levels of IL-36α, IL-36β, IL-36γ, IL-17A, IL-17C, IFN-γ, TNF, IL-6, IL-8 all decreased, and those of IL-36α, IL-36β, IL-17A, IL-17C, and IL-6 were statistically significant. There was no recurrence after 2 to 8 months of treatment. No other adverse event was recorded apart from one patient who experienced an upper respiratory infection in the first week. Conclusion: Spesolimab might be a prospective option for children aged 4 to 12 years. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease characterized by persistent symptoms and sudden flares of painful, sterile pustules, and may be accompanied by systemic inflammation. Ongoing symptoms of GPP can have a serious impact on patient quality of life, morbidity, and mortality, and severe flares may be life-threatening if left untreated. Guidelines have been developed for the treatment of GPP flares; however, health care professionals and patients are lacking guidance on the management of long-term, persistent symptoms of GPP. Spesolimab is the only FDA-approved treatment for GPP and is approved for use in adults and pediatric patients aged 12 years or older and weighing at least 40 kg. Spesolimab recently gained FDA approval as a subcutaneous injection to treat GPP when patients are not experiencing a flare. In this podcast episode, we discuss what is known about the chronic disease burden of GPP and how persistent symptoms affect quality of life when patients are not experiencing a flare. We address the need for treatment guidelines for chronic GPP and discuss the results of the EFFISAYIL® 2 clinical trial, which led to the approval of the subcutaneous formulation of spesolimab to treat GPP when patients are not experiencing a flare. Finally, we discuss what can be done to improve the treatment of patients with chronic GPP, both while experiencing a flare, and while living with persistent symptoms. [ABSTRACT FROM AUTHOR]

Inflammatory diseases that are driven by several pro‐inflammatory cytokines has resulted in in the development of targeted therapies across different disease settings. Interleukin (IL)‐36 cytokines have been implicated in several inflammatory diseases. In this review we describe the scientific evidence surrounding the use of the IL‐36 receptor (IL‐36R)‐targeting antibody, spesolimab, in IL‐36‐mediated skin diseases: generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP), hidradenitis suppurativa, and Netherton syndrome (NS). Spesolimab, a high affinity, specific, humanized, antagonistic immunoglobulin G1 antibody, targets the IL‐36R at a binding site distinct from its agonists, IL‐36α/β/γ, and at least one endogenous antagonist, IL‐36R antagonist. In vitro and in vivo data for spesolimab show effective inhibition of IL‐36R‐mediated signaling pathways, and six Phase I studies in healthy volunteers presented a favorable safety and pharmacokinetic (PK) profile, leading to the development of a clinical trial program to evaluate spesolimab in the treatment of IL‐36R‐mediated diseases. Six studies (including an expanded access program) have evaluated the efficacy, safety, PKs, and pharmacogenomics of spesolimab in patients with GPP flares. Spesolimab treatment of GPP flares resulted in rapid and sustained improvements in pustular and skin clearance, and clinically significant improvements in patient‐reported symptoms and quality of life. Spesolimab also significantly reduces the risk of GPP flares and flare occurrence, preventing disease worsening and has a favorable safety profile. There have been three trials of spesolimab in PPP; further evaluation is needed to better define those patients who might benefit from the treatment. A trial of spesolimab in NS is ongoing, while other spesolimab trials suggest that IL‐36 may only play a secondary role in the pathogenesis of atopic dermatitis. In conclusion, research into spesolimab has provided much needed insight into the role of IL‐36 in the human immune system and the mechanism behind IL‐36‐mediated inflammatory diseases. Spesolimab provides an efficacious targeted treatment for GPP, a disease with a high unmet medical need. [ABSTRACT FROM AUTHOR]

Introduction: Generalized pustular psoriasis (GPP) is a rare and potentially lifethreatening auto-inflammatory disease. Currently, there are no consensusbased guidelines or universally accepted treatments. Biologics represent a potential therapeutic option. This study systematically assessed the efficacy and safety of biologics in GPP. Methods: Relevant studies from three databases were systematically searched until June 28, 2024. Statistical information, including the single-arm proportion rate of the outcomes and 95% confidence intervals (CIs), was analyzed to determine treatment effects. Heterogeneity was assessed using I² values, and subgroup analyses were performed based on drug targets and treatment durations. Data were quantitatively synthesized using a random-effects metaanalysis. Analyses were performed using R statistical software version 4.4.0. Results: A total of 329 patients from 16 studies were included. The proportion of responders treated with IL-36 inhibitors and IL-17 inhibitors is higher than those treated with TNF-a inhibitors and IL-23 inhibitors. IL-36 inhibitors appear to achieve the highest response rates between 4 and 8 weeks, while IL-17 inhibitors, TNF-alpha inhibitors, and IL-23 inhibitors show a gradual increase in response rates up to 12 weeks. IL-36 inhibitors achieve a 40% (95% CI: 27%-54%) GPPASI75 response rate and a 55% (95% CI: 41%-68%) GPPGA (0,1) response rate within 2 weeks, significantly outperforming other biologics. The recurrence rates of GPP within 52 weeks, ranked from highest to lowest, are: IL-36 inhibitors (21% [95% CI: 9%-28%]), TNF-alpha inhibitors (20% [95% CI: 2%-46%]), IL-17 inhibitors (15% [95% CI: 1%-37%]), and IL-23 inhibitors (5% [95% CI: 0%-29%]). Additionally, 6% (95% CI: 1%-11%) of patients experienced severe adverse events. Discussion: This meta-analysis highlights the efficacy and safety of biologics in patients with GPP, offering valuable evidence to guide future clinical practice. ILFrontiers 36 inhibitors show a faster and more substantial clinical response in GPP compared to other biologics. Further research is necessary to assess their role in specific subpopulations and to evaluate their potential long-term effects on flare prevention. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. However, the pathogenesis of GPP has not been fully elucidated. Although RNA-binding proteins (RBPs) and the alternative splicing (AS) process are essential for regulating post-transcriptional gene expression, their roles in GPP are still unclear. We aimed to elucidate the regulatory mechanisms to identify potential new therapeutic targets. Here, We analyzed an RNA sequencing (RNA-seq) dataset (GSE200977) of peripheral blood mononuclear cells (PBMCs) of 24 patients with GPP, psoriasis vulgaris (PV), and healthy controls (HCs) from the Gene Expression Omnibus (GEO) database. We found that the abnormal alternative splicing (AS) events associated with GPP were mainly “alt3p/alt5p”, and 15 AS genes were differentially expressed. Notably, the proportions of different immune cell types were correlated with the expression levels of regulatory alternatively spliced genes (RASGs): significant differences were observed in expression levels of DTD2, NDUFAF3, NBPF15, and FBLN7 in B cells and ARFIP1, IPO11, and RP11-326L24.9 in neutrophils in the GPP samples. Furthermore, We identified 32 differentially expressed RNA-binding proteins (RBPs) (18 up-regulated and 14 down-regulated). Co-expression networks between 14 pairs of differentially expressed RBPs and RASGs were subsequently constructed, demonstrating that these differentially expressed RBPs may affect the progression of GPP by regulating the AS of downstream immune/inflammatory-related genes such as LINC00989, ENC1 and MMP25-AS1. Our results were innovative in revealing the involvement of inflammation-related RBPs and RASGs in the development of GPP from the perspective of RBP-regulated AS. [ABSTRACT FROM AUTHOR]

Abstract Introduction Data on generalized pustular psoriasis (GPP) in Poland are limited. Therefore, this study aimed to evaluate the demographic and clinical characteristics of Polish patients with GPP. In addition, the effect of the frequency of disease flares and the concomitant presence of psoriasis vulgaris (PV) on patient characteristics was evaluated. Methods In this retrospective study, medical records of patients hospitalized for GPP in dermatology departments of the Polish Generalized Pustular Psoriasis Group were analyzed. Results A total of 90 patients from 14 dermatology centers were included. The median age of patients was 59 (range, 5–85) years, and most patients were female (68.9%). The most common comorbidity was hypertension (43.3%), followed by cardiovascular diseases, diabetes, and hyperlipidemia. The median duration of GPP was 3 years, and the median number of flares was 2. Hospitalization was required in 67% of flares. The main triggering factors were drugs (20.5%) and infections (19.3%). Women and men with GPP differed in terms of age (p

Background: Generalized pustular psoriasis (GPP) is an uncommon variant of psoriasis. Clinical characteristics of GPP are limited due to its relatively low prevalence worldwide. Thus, the region-specific phenotypic differences between GPP and severe plaque psoriasis (SPP) remained not fully clarified. Objectives: This study aimed to compare the gender distribution, disease onset, clinical features, medical comorbidities, associated symptoms, laboratory findings, and potential precipitating factors of GPP and SPP in a single center in tropical Taiwan. Methods: A retrospective review was conducted for GPP and SPP in a tertiary medical center from 2003 to 2023. The GPP Area and Severity Index (GPPASI) and GPP Physician Global Assessment (GPPGA) score were used to measure the severity of GPP. Results: A total of 26 patients with GPP (mean age: 48.2 years) and 50 patients with SPP (defined as psoriasis area and severity index over 20 and undergoing biological agents more than 1 year, mean age: 41.3 years) were included in this study. Forty-six percentage of the GPP patients had a preceding history of psoriasis. While there was no gender or age predominance, patients with GPP tended to develop fever, hypertension, upper respiratory tract infection, leukocytosis, elevated C-reactive protein (CRP) levels, scalp involvement, be hospitalized and for a long time, along with allergy history of medications (diclofenac, ampicillin, and ceftriaxone), as compared to those with SPP. Hepatitis B virus and hepatitis C virus infections were less prevalent in GPP patients (with 15.4% and 3.8%, compared to 30.0% and 8.0% in SPP, respectively, although not statistically significant). The highest GPPASI and GPPGA scores occurred in young patients of GPP, but they are not associated with diseases of hypertension, hyperglycemia, or hyperlipidemia. Conclusion: Patients with GPP in Taiwan tended to have a higher hospitalization rate and longer mean hospitalization time along with increased occurrence of fever, leukocytosis, elevated CRP levels, and drug allergy. The younger patients of GPP tended to have higher GPPASI and GPPGA scores than the elder ones.

Shi-Fan Ruan,1– 3,&ast; Xinhong Su,1,2,&ast; Zhixun Xiao,1,2,&ast; Yihua Zhang,1,2,&ast; Tingting Lin,1,2 Renwei Luo,1,2 Niu Xiang,1,2 Bo Cheng,1– 3 Ting Gong,4 Chao Ji1– 3 1Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 2Key Laboratory of Skin Cancer of Fujian Higher Education Institutions, Fuzhou, Fujian, 350000, People’s Republic of China; 3Fujian Provincial Clinical Research Center for Immune Skin Diseases, Fuzhou, Fujian, 350000, People’s Republic of China; 4Central Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Gong, Central Laboratory, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350000, People’s Republic of China, Email gongtingfy@fjmu.edu.cn Chao Ji, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350000, People’s Republic of China, Email jichaofy@fjmu.edu.cnPurpose: Recent studies have shown that novel biologics may provide significant clinical benefits for patients with generalized pustular psoriasis (GPP). Ustekinumab and secukinumab have been approved in Japan for GPP treatment in adult patients. However, the differences in efficacy and safety of these two drugs in GPP are not known.Aim: Based on the genetic background, we aimed to compare the efficacy and safety of secukinumab and ustekinumab in patients with GPP.Methods: Patients with moderate to severe GPP who were treated with ustekinumab/secukinumab at our department from July 2019 to May 2022 were included in this study and followed up for 48 weeks. The difference in efficacy between ustekinumab and secukinumab was evaluated by assessing changes in body temperature, laboratory indices, recovery of skin lesions, and changes in quality of life. Additionally, we collected patients’ saliva for genotyping and explored the effect of CARD14 genetic mutations on clinical efficacy.Results: A total of 65 patients (32 adults and 33 children) with moderate to severe GPP were included in this study. 31 patients received ustekinumab therapy, and 34 patients were treated with secukinumab. Secukinumab demonstrated superiority to ustekinumab, as evidenced by a higher GPPASI 90 response at week 2. Additionally, the efficacy of ustekinumab and secukinumab was found to be independent of the presence of the CARD14 mutation.Conclusion: Secukinumab is superior to ustekinumab in rapidly clearing the skin and improving health-related quality of life. Moreover, the responses to ustekinumab/secukinumab in patients were not influenced by CARD14 gene mutations.Keywords: generalized pustular psoriasis, secukinumab, ustekinumab, clinical efficacy, safety, gene mutations

Abstract Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients’ quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980–September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy.

Abstract Introduction Generalized pustular psoriasis (GPP) is a rare and severe psoriasis subtype characterized by the rapid onset of coalescing sterile pustules over broad body areas and systemic inflammation. Data on its clinical course and outcomes in Taiwan are limited. We evaluated the clinical profile and outcomes of patients with GPP flares in Taiwan. Methods This retrospective analysis included adult patients with moderate-to-severe GPP flares occurring in January 2008–December 2021. Data were extracted from medical charts and electronic health records in the Chang Gung Research Database. Statistical analyses were performed using SAS for Windows (version 9.4). Multivariate Poisson regression models were built to investigate different predictors of GPP flare rate. Results Thirty-four patients with 81 moderate-to-severe GPP flares were identified. Of the 14 patients undergoing genetic analysis, 10 (71.4%) had an IL36RN mutation. Patients’ mean age at the index GPP flare was 47.1 ± 16.5 years; 58.0% of the flares were severe, while 42.0% were moderate. Overall, 96.3% of GPP flares were treated with at least one systemic therapy, acitretin being the most prescribed (85.2%), followed by cyclosporine (45.7%) and methotrexate (18.5%). After treatment, the proportion of flares responding positively increased from 0% on day 2 to 6.2% by week 12. Patients were newly diagnosed with psoriasis (23.5%), hypertension (20.6%), diabetes mellitus (14.7%), psoriatic arthritis (2.9%), malignant tumor (8.8%), and depression/anxiety (2.9%) after enrollment. Complications occurring within 12 weeks of GPP flares included arthritis (25.9% of the flares), skin infection (8.6%), and other infections (2.5%). No fatalities were reported. In the multivariate model, former smokers, patients with hepatic disease, and patients with psoriatic arthritis had an increased GPP rate ratio (RR) of 13.33 (95% confidence interval, CI, 2.87–61.78), 14.08 (95% CI 3.04–65.29), and 34.84 (95% CI 4.77- 254.42), respectively. Contrarily, obese and rheumatoid arthritis patients had a lower GPP rate ratio of 0.21 (95% CI 0.08–0.54) and 0.07 (95% CI 0.006–0.78), respectively. Conclusions Our findings highlight the complexity of GPP flare presentations and the need for individualized, patient-centered management approaches and continued research to improve affected individuals’ care and outcomes.

Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients' quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980–September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy. Plain Language Summary: Generalized pustular psoriasis (GPP) is a rare, chronic skin condition characterized by painful, sterile pustules that can occur all over the body. These pustules may also be accompanied by systemic inflammation, which can lead to serious health complications. GPP significantly impacts patients' quality of life and can even be life-threatening. Because the disease is so rare, treatment guidelines have typically been based on those for plaque psoriasis. However, these guidelines do not specifically address the unique needs of GPP. In this review, we analysed the published literature on GPP management, focussing on treatment efficacy, safety and quality of life outcomes. We searched the literature databases Embase and MEDLINE for articles published between 1980 and September 2023. In total, we identified 118 publications on this topic, covering a wide range of therapies; only one of these therapies, spesolimab, reported results from placebo-controlled randomized trials. Based on these trials, spesolimab is now approved for GPP treatment in the USA, Japan, China, the EU and several other countries. Some other therapies are approved exclusively in Japan and Taiwan based on small, open-label studies in the absence of higher-quality data. To date, comparing treatments has been challenging because of different clinical outcomes used to measure effectiveness. However, well-defined endpoints specific to GPP have recently been developed and used in trials. In conclusion, our review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the best treatment strategy. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical features, treatment options, and outcomes of impetigo herpetiformis. Methods A retrospective analysis was conducted on the clinical features, histopathological findings, treatment approaches, and outcomes of five patients with impetigo herpetiformis treated in our hospital. Results The patients exhibited various presentations: one patient developed impetigo herpetiformis during early pregnancy, three during mid-pregnancy, and one during late pregnancy. All patients had elevated inflammatory markers. Two patients had a history of acrodermatitis continua of Hallopeau, presenting with erythema annulare centrifugum-like lesions covered with dense pustules and fever. In contrast, two other patients who underwent embryo transplantation without a history of psoriasis exhibited skin lesions resembling von Zumbusch-type pustular psoriasis but without fever. Initially, all patients were treated with glucocorticoids, but their skin lesions remained poorly controlled. Subsequently, three patients underwent induction of labor in late pregnancy, while two patients received treatment with biological agents. All five pregnancies resulted in premature births, but all fetuses survived. Conclusion The skin manifestations of impetigo herpetiformis differ between patients undergoing embryo transplantation and those with natural conception. A history of acrodermatitis continua of Hallopeau, embryo transplantation due to autoimmune infertility, and early onset of the disease indicate a severe prognosis. The use of biological agents may potentially improve the outcomes in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening inflammatory skin disease. Interleukin (IL)-36 signalling may play a central role in GPP pathogenesis. Spesolimab is a humanized anti-IL-36 monoclonal antibody inhibiting the IL-36 signalling pathway. Here, we investigated the pharmacokinetics and safety of spesolimab in healthy Chinese subjects. Methods: In this Phase 1, single-dose, parallel-group, open-label study, healthy Chinese subjects aged 18–45 years received a single spesolimab dose by intravenous infusion (IV; 450 mg, 900 mg, or 1200 mg) or subcutaneous (SC) administration (300 mg or 600 mg). Primary endpoints were spesolimab exposure (area under the plasma concentration-time curve and maximum plasma concentration); secondary endpoints were treatment-emergent adverse events (TEAEs) and drug-related adverse events (AEs). Results: Fifty subjects received IV (n = 30) or SC (n = 20) spesolimab (n = 10 per dose group); 60.0% were male, mean ± standard deviation age was 31.5 ± 6.6 and 31.0 ± 6.5 years in the IV and SC groups, respectively. Spesolimab exposure increased in a dose-proportional manner in both groups. TEAEs were reported in 83.3% and 80.0% of subjects in the IV and SC groups, the most common TEAE was upper respiratory tract infection (20.0% and 25.0%, respectively). One serious AE of hand fracture was reported in the 900 mg IV group that was not considered drug-related. Drug-related AEs were reported in 53.3% and 55.0% of subjects in the IV and SC groups. All laboratory-related AEs were mild and resolved. Conclusion: Spesolimab exposure increased in a dose-proportional manner after a single dose by IV and SC administration. Spesolimab was well tolerated in healthy Chinese subjects. Clinical Trial Registration: Clinicaltrials.gov registration: NCT04390568. [ABSTRACT FROM AUTHOR]

Introduction: Generalized pustular psoriasis (GPP) is a rare and severe psoriasis subtype characterized by the rapid onset of coalescing sterile pustules over broad body areas and systemic inflammation. Data on its clinical course and outcomes in Taiwan are limited. We evaluated the clinical profile and outcomes of patients with GPP flares in Taiwan. Methods: This retrospective analysis included adult patients with moderate-to-severe GPP flares occurring in January 2008–December 2021. Data were extracted from medical charts and electronic health records in the Chang Gung Research Database. Statistical analyses were performed using SAS for Windows (version 9.4). Multivariate Poisson regression models were built to investigate different predictors of GPP flare rate. Results: Thirty-four patients with 81 moderate-to-severe GPP flares were identified. Of the 14 patients undergoing genetic analysis, 10 (71.4%) had an IL36RN mutation. Patients' mean age at the index GPP flare was 47.1 ± 16.5 years; 58.0% of the flares were severe, while 42.0% were moderate. Overall, 96.3% of GPP flares were treated with at least one systemic therapy, acitretin being the most prescribed (85.2%), followed by cyclosporine (45.7%) and methotrexate (18.5%). After treatment, the proportion of flares responding positively increased from 0% on day 2 to 6.2% by week 12. Patients were newly diagnosed with psoriasis (23.5%), hypertension (20.6%), diabetes mellitus (14.7%), psoriatic arthritis (2.9%), malignant tumor (8.8%), and depression/anxiety (2.9%) after enrollment. Complications occurring within 12 weeks of GPP flares included arthritis (25.9% of the flares), skin infection (8.6%), and other infections (2.5%). No fatalities were reported. In the multivariate model, former smokers, patients with hepatic disease, and patients with psoriatic arthritis had an increased GPP rate ratio (RR) of 13.33 (95% confidence interval, CI, 2.87–61.78), 14.08 (95% CI 3.04–65.29), and 34.84 (95% CI 4.77- 254.42), respectively. Contrarily, obese and rheumatoid arthritis patients had a lower GPP rate ratio of 0.21 (95% CI 0.08–0.54) and 0.07 (95% CI 0.006–0.78), respectively. Conclusions: Our findings highlight the complexity of GPP flare presentations and the need for individualized, patient-centered management approaches and continued research to improve affected individuals' care and outcomes. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a chronic, rare, and potentially lifethreatening inflammatory disease, characterized by the rapid and widespread eruption of small, sterile pustules with surrounding skin erythema. Abnormal signaling of the interleukin-36 (IL-36) pathway appears to have a central role in GPP immunopathology, and provides a rational therapeutic target. Spesolimab is a first-in-class humanized monoclonal antibody that binds specifically to the IL-36 receptor, and antagonizes IL-36 signaling. Spesolimab obtained regulatory approval in the United States (US) in September 2022 for use in the treatment of GPP flares in adults, and was subsequently approved for GPP flare treatment in many other countries across the world. Recently, regulatory approval was granted for subcutaneous dosing of spesolimab for treatment of GPP when not experiencing a flare. Here, we review data from two key clinical trials that supported the initial US regulatory approval; namely, the phase 1 proof-ofconcept trial (ClinicalTrials.gov ID, NCT02978690), and Effisayil™ 1 (NCT03782792), which remains the largest and only randomized clinical trial in patients experiencing GPP flares published to date. In the phase 1 proof-ofconcept trial, a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score of 0 or 1 (clear or almost clear skin) was attained in 5/7 (71%) patients by week 1 and in all 7 patients by week 4; and the mean percent improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score from baseline was 59.0% at week 1, 73.2% at week 2, and 79.8% at week 4. In Effisayil™ 1, a GPPGA pustulation subscore of 0 (no visible pustules) was achieved in 19/35 (54%) patients receiving spesolimab at the end of week 1, versus 1/18 (6%) receiving placebo (difference, 49 percentage points; 95% confidence interval [CI], 21 to 67; P<0.001); and a GPPGA total score of 0 or 1 was achieved by 15/35 (43%) patients in the spesolimab group, versus 2/18 (11%) patients in the placebo group (difference, 32 percentage points; 95% CI, 2 to 53; P = 0.02). Infections at week 1 were reported in 6/35 (17%) patients receiving spesolimab and in 1/18 (6%) patients receiving placebo. These data demonstrate the efficacy and safety of spesolimab in providing rapid and sustained clinical improvement for patients with GPP flares, which translates into improved quality of life, by offering a targeted therapy for GPP. [ABSTRACT FROM AUTHOR]

Background: Generalized pustular psoriasis (GPP) is an uncommon variant of psoriasis. Clinical characteristics of GPP are limited due to its relatively low prevalence worldwide. Thus, the region-specific phenotypic differences between GPP and severe plaque psoriasis (SPP) remained not fully clarified. Objectives: This study aimed to compare the gender distribution, disease onset, clinical features, medical comorbidities, associated symptoms, laboratory findings, and potential precipitating factors of GPP and SPP in a single center in tropical Taiwan. Methods: A retrospective review was conducted for GPP and SPP in a tertiary medical center from 2003 to 2023. The GPP Area and Severity Index (GPPASI) and GPP Physician Global Assessment (GPPGA) score were used to measure the severity of GPP. Results: A total of 26 patients with GPP (mean age: 48.2 years) and 50 patients with SPP (defined as psoriasis area and severity index over 20 and undergoing biological agents more than 1 year, mean age: 41.3 years) were included in this study. Forty-six percentage of the GPP patients had a preceding history of psoriasis. While there was no gender or age predominance, patients with GPP tended to develop fever, hypertension, upper respiratory tract infection, leukocytosis, elevated C-reactive protein (CRP) levels, scalp involvement, be hospitalized and for a long time, along with allergy history of medications (diclofenac, ampicillin, and ceftriaxone), as compared to those with SPP. Hepatitis B virus and hepatitis C virus infections were less prevalent in GPP patients (with 15.4% and 3.8%, compared to 30.0% and 8.0% in SPP, respectively, although not statistically significant). The highest GPPASI and GPPGA scores occurred in young patients of GPP, but they are not associated with diseases of hypertension, hyperglycemia, or hyperlipidemia. Conclusion: Patients with GPP in Taiwan tended to have a higher hospitalization rate and longer mean hospitalization time along with increased occurrence of fever, leukocytosis, elevated CRP levels, and drug allergy. The younger patients of GPP tended to have higher GPPASI and GPPGA scores than the elder ones. [ABSTRACT FROM AUTHOR]

Generalized Pustular Psoriasis (GPP) is a rare and severe subtype of psoriasis that significantly impacts patients' quality of life. Until recently, no specific treatment modalities were available, and treatment for GPP followed the guidelines for the treatment of plaque psoriasis, consisting of conventional treatments, such as retinoids, methotrexate, and even biologics, which although effective in some cases, may be associated with significant side effects, necessitating more effective and safe options. The pathophysiology of Generalized Pustular Psoriasis is complex and not fully understood, but there is some overlap with the pathogenesis of Plaque Psoriasis. In GPP, the innate immune system seems to play a more significant role, with the interleukin (IL)-36 pathway being fundamentally involved. Spesolimab and imsidolimab, two recently developed therapeutic agents, target the IL-36 inflammatory pathway by binding to the IL-36 receptor (IL-36R). Both biologics have already been evaluated in phase 1 and 2 clinical trials and have shown promising results in terms of safety and efficacy. IL-36 receptor inhibitors demonstrated great efficacy and good safety profile in the management of patients with GPP, demonstrating their potential to emerge as a leading treatment option. This review aims to explore and summarize the current scientific literature on the most recently developed treatments for GPP. [ABSTRACT FROM AUTHOR]

AbstractBackground Real-world data on health-related quality of life (HRQoL) in generalized pustular psoriasis (GPP) are scarce and studies have been restricted in terms of instruments used for assessments.Objective To assess generic and dermatology-specific HRQoL of patients with GPP compared with patients with plaque psoriasis using real-world data from the Swedish National Register for Systemic Treatment of Psoriasis.Methods Cross-sectional data from 2006 to 2021 including 7041 individuals with plaque psoriasis without GPP and 80 patients with GPP, of which 19% also had plaque psoriasis. Total scores for the EuroQol-5 Dimensions (EQ-5D) and Dermatology Life Quality Index (DLQI), as well as degree of severity within the instruments’ dimensions/questions, were compared between patient groups.Results EQ-5D scores were significantly (p

AbstractObjectives Generalized pustular psoriasis (GPP) is a rare, life-threatening skin inflammatory disorder. This study aimed to describe the disease course, treatment strategies, and healthcare utilization among patients with GPP in Portugal.Methods This multicentric, observational, retrospective study included consecutive adult patients with GPP undergoing a dermatology evaluation in different reporting institutions by experienced dermatologists between 2002 and 2023.Results A total of 59 patients were assessed. Most of the cohort had a previous history of plaque psoriasis (71%) and 83% presented at least one comorbidity. At the initial encounter, 64% of the cohort needed hospitalization. Systemic involvement was common, including fever (37%), and elevated white blood cell count and erythrocyte sedimentation rate/C-reactive protein (49%). Nearly, 73% of patients initiated systemic drugs, and 70% had to discontinue the first treatment. During the study, 98% of patients experienced at least one flare. At the last visit, 3.4% of patients had died, and 71.2% exhibited signs of active disease despite undergoing treatment.Conclusions Our study demonstrates that GPP is a chronic, debilitating condition associated with systemic involvement, frequent flares, and hospitalizations, despite receiving multiple systemic treatments. Improved disease awareness and new treatments are needed to improve patient care and decrease the burden of the disease.

AbstractGeneralized pustular psoriasis (GPP) in pregnancy can lead to severe complications for both mother and fetus. The treatment of this disease is challenging, especially in recalcitrant and severe cases. Until present, there are no evidence-based guidelines for the treatment of GPP in pregnancy. Spesolimab, a human monoclonal antibody against the IL-36 receptor, has recently attracted attention as a new therapy for GPP flare. This biologic provides rapid and sustained control of symptoms of GPP flare, although its use in pregnant women has not been reported to date. Here, we report a pregnant woman with refractory GPP who did not respond well to systemic steroids. Administration of spesolimab resulted in complete control of the disease and the birth of a healthy baby. Our case demonstrates that IL-36RN inhibitors are a potentially effective and safe treatment option for GPP in pregnancy.

AbstractThe purpose of the article: Generalized pustular psoriasis (GPP) is a rare auto-inflammatory disease. Patients with GPP may develop life-threatening complications, including sepsis, acute renal failure, neutrophilic cholangitis, high-output congestive heart failure, acute respiratory distress syndrome and death. The therapy of GPP is very limited and the course of the disease is unpredictable.Materials and methods: We report a 60-year-old woman presenting with widespread and confluent erythematous-desquamative plaques with numerous small pustules covering almost 70% of the body surface area. Over the past years patient had undergone different types of conservative treatment regimens including topical therapy, acitretin, cyclosporin, methotrexate and long-term treatment with systemic corticosteroids. Considering the patient’s overall clinical condition, we proceed to initiate the biologic therapy with guselkumab.Results: Guselkumab (anti-IL-23) in the standard dose of 100 mg was administered subcutaneously at weeks 0, 4 and followed by a maintenance dose every 8 weeks. The remission of GPP was observed already after 12 weeks of treatment. The maintenance treatment in the period of 18 months shows stable clinical response.Conclusions: Our results support the evidence that guselkumab could provide an effective therapeutic approach in the treatment of GPP.

The purpose of the article: Generalized pustular psoriasis (GPP) is a rare auto-inflammatory disease. Patients with GPP may develop life-threatening complications, including sepsis, acute renal failure, neutrophilic cholangitis, high-output congestive heart failure, acute respiratory distress syndrome and death. The therapy of GPP is very limited and the course of the disease is unpredictable. Materials and methods: We report a 60-year-old woman presenting with widespread and confluent erythematous-desquamative plaques with numerous small pustules covering almost 70% of the body surface area. Over the past years patient had undergone different types of conservative treatment regimens including topical therapy, acitretin, cyclosporin, methotrexate and long-term treatment with systemic corticosteroids. Considering the patient’s overall clinical condition, we proceed to initiate the biologic therapy with guselkumab. Results: Guselkumab (anti-IL-23) in the standard dose of 100mg was administered subcutaneously at weeks 0, 4 and followed by a maintenance dose every 8weeks. The remission of GPP was observed already after 12weeks of treatment. The maintenance treatment in the period of 18months shows stable clinical response. Conclusions: Our results support the evidence that guselkumab could provide an effective therapeutic approach in the treatment of GPP. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) in pregnancy can lead to severe complications for both mother and fetus. The treatment of this disease is challenging, especially in recalcitrant and severe cases. Until present, there are no evidence-based guidelines for the treatment of GPP in pregnancy. Spesolimab, a human monoclonal antibody against the IL-36 receptor, has recently attracted attention as a new therapy for GPP flare. This biologic provides rapid and sustained control of symptoms of GPP flare, although its use in pregnant women has not been reported to date. Here, we report a pregnant woman with refractory GPP who did not respond well to systemic steroids. Administration of spesolimab resulted in complete control of the disease and the birth of a healthy baby. Our case demonstrates that IL-36RN inhibitors are a potentially effective and safe treatment option for GPP in pregnancy. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP), being a chronic inflammatory systemic disease, significantly reduces the quality of life of patients, leads to disability and increases the risk of mortality. Representing one of the most severe variants of the disease, GPP has its own features of pathogenesis, which distinguish it from plaque and other forms of dermatosis. Presently, the key factor in the development of the systemic process in GPP is considered to be a decrease in the expression or activity of IL-36ra receptor antagonists due to mutation of the IL-36RN gene, and as a result of this, excessive activity of IL-36 agonists and accumulation of neutrophil granulocytes in the epidermis. Based on the features of clinical manifestations in the form of multiple painful pustules accompanied by fever up to 40° C, characteristic changes in laboratory parameters in the form of increased markers of inflammation (leukocyte levels with neutrophil shift in peripheral blood, C-reactive protein), GPP needs to be differentiated from a number of diseases accompanied by similar symptoms: subcorneal pustular dermatosis Sneddon–Wilkinson, Sweet's syndrome, a herpes infection. The features of the pathogenesis of GPP determine the difficulties in the treatment of medicines that are successfully used in the treatment of plaque psoriasis, including methotrexate, cyclosporine, retinoids, TNF-α inhibitor, interleukin-17 and -23 inhibitors, as well as their combinations. A clinical case of a severe continuously recurrent resistant to therapy with cytostatics and genetically engineered preparations is presented, the diagnosis of which was complicated by a contradictory pathomorphological picture.

Background: Generalized pustular psoriasis (GPP) is a rare skin disease characterized by episodes of widespread sterile pustules. Methods: A retrospective cohort study using data from the US IBM MarketScan Commercial and Optum Clinformatics Data Mart databases between October 1, 2015 and March 31, 2020 was performed to describe adherence and persistence to biologics in patients with GPP. Patients were aged ≥18 years with newly diagnosed GPP (International Classification of Diseases code L40.1) and had ≥1 inpatient or ≥2 outpatient claims. Results: Biologics were dispensed to 110 of 502 (22%) and 73 of 528 (14%) patients from MarketScan and Optum databases, respectively. The mean proportion of days covered (PDC) (range) was similar in both databases (MarketScan, 65% [8%-100%]; Optum, 59% [8%-99%]), and good adherence (≥80% PDC) was uncommon (MarketScan, 36%; Optum, 24%). Mean (standard deviation) persistence was similar in both databases (MarketScan, 287 [122] days; Optum, 261 [134] days). In Optum, the mean PDC was similar between age categories; good adherence was more common in patients aged 18 to 64 years (28%) versus ≥65 years (13%). Mean persistence was longer in patients aged 18 to 64 years (267 days) versus ≥65 years (242 days). Conclusions: Overall, adherence and persistence were generally poor and varied according to the biologic class, database, and age. Improving adherence may help improve GPP treatment outcomes.

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening skin disease characterized by relapsing and remitting flares of sterile neutrophilic pustules and systemic inflammation. The definition of GPP is inconsistent globally, with large discrepancies in clinical management. To provide clinical guidance on managing GPP, we conducted a systematic literature search for articles published within the last decade on PubMed and the Cochrane Library in October 2022 and held four consensus meetings with 12 Taiwanese dermatologists between October 2022 and July 2023. Upon review of 153 articles, we agreed to adopt the European Rare and Severe Psoriasis Expert Network GPP definition with additional clarifications on pustular flares in psoriatic plaques, circinate or annular lesions, and localized pustules. We also drafted a diagnostic algorithm to facilitate GPP diagnosis. Twenty-seven statements on GPP treatment reached consensus. We recommend using an oral retinoid or spesolimab injection for the first-line treatment in both acute (treating flares) and maintenance (preventing flares) settings in adults with GPP. For infants and juveniles with GPP, retinoids are recommended as a first-line treatment. Evidence for other conventional and investigational therapies was reviewed, and a treatment algorithm was proposed. We hope this consensus provides practical guidance for clinicians in Taiwan and helps improve outcomes for GPP patients.

Objective To evaluate the efficacy and safety of Spesolimab in the treatment of generalized pustular psoriasis(GPP). Methods A 30 years old female with GPP was intravenously given 900 mg of Spesolimab once. The safety and the changes in modified generalized pustular psoriasis area severity index (GPPASI) and generalized pustular psoriasis physician global assessment (GPPGA) were evaluated. Results After 1 week of the treatment, the GPPGA reached 2. After 2 months of the treatment, pustules almost completely subsided and both GPPASI and GPPGA reached 1. During the treatment, the patient developed anaphylactic adverse reactions, which were improved following the injection of betamethasone, antihistamine and symptomatic therapy. Conclusion Spesolimab is an effective and safe agent for the treatment of generalized pustular psoriasis.

Hao Wu, Yan Na Shen, Zhongxiao Wu, Feng Mao, You Gang Ren, Li Zhang Department of Dermatology, Ningbo No 6 Hospital, Ningbo, 315040, People’s Republic of ChinaCorrespondence: Li Zhang, Email lishay1022@hotmail.comAbstract: Although the use of biologics has led to great improvement in psoriasis patients, the treatment of psoriasis during pregnancy still faces many challenges. We herein report on a 29-year-old pregnant woman treated with ustekinumab for generalized pustular psoriasis. Upon becoming pregnant, the woman underwent continued treatment with ustekinumab in the first trimester. We also considered the need for neonatal vaccination. The patient discontinued ustekinumab therapy in the second trimester, and during the period of drug discontinuation we noted a slight rash recurrence. The patient was treated with ultraviolet B phototherapy and topical corticosteroids, and the rash was localized to the abdomen. However, in the 27th week of pregnancy, the patient was infected with COVID-19, which made the condition worse. The rash erupted rapidly and spread throughout her body, and she experienced a high fever with her blood count showing augmented numbers of white blood cells. The patients self-administered 0.3 g of acetaminophen three times per day, and after four days her core body temperature was 38.0°C; the rash, however, did not diminish. We diagnosed an outbreak of generalized pustular psoriasis and treated the patient with ustekinumab. The rash resolved quickly, and a healthy newborn was delivered by caesarean section at 39 weeks.Keywords: Ustekinumab, interleukin-12/-23, generalized pustular psoriasis, pregnancy, COVID-19

This review explores the intricate relationship between generalized pustular psoriasis (GPP) and various systemic diseases, shedding light on the broader impacts of this severe skin condition beyond its primary dermatological manifestations. GPP is identified as not only a profound contributor to skin pathology but also a significant risk factor for systemic diseases affecting cardiovascular, hepatic, renal, pulmonary, and skeletal systems, as well as associated with an increased incidence of anemia, depression, anxiety, and arthritis. The research highlights the complex interplay of cytokines, particularly IL-17 and IL-36, which are central to the pathophysiology of GPP and implicated in the exacerbation of systemic conditions. Key findings indicate a higher incidence of cardiovascular events in GPP patients compared to those with other severe forms of psoriasis, notably with a stronger correlation between myocardial infarction history and GPP development. Liver disturbances, frequently reversible upon psoriasis remission, suggest a cytokine-mediated link to hepatic health. Renal dysfunction appears elevated in GPP sufferers, with IL-17 and IL-36 potentially driving renal fibrosis. Similarly, interstitial lung disease and osteoporosis in GPP patients underscore the systemic reach of inflammatory processes initiated in the skin. The associations with anemia, depression, anxiety, and arthritis further complicate the clinical management of GPP, requiring a multidisciplinary approach. The study concludes that managing GPP effectively requires a holistic approach that addresses both the cutaneous and systemic dimensions of the disease, advocating for continued research into the mechanisms that connect GPP with broader health implications to refine therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy and safety of Spesolimab in the treatment of generalized pustular psoriasis (GPP). Methods A 30 years old female with GPP was intravenously given 900 mg of Spesolimab once. The safety and the changes in modified generalized pustular psoriasis area severity index (GPPASI) and generalized pustular psoriasis physician global assessment (GPPGA) were evaluated. Results After 1 week of the treatment, the GPPGA reached 1. After 1 months of the treatment, pustules almost completely subsided and both GPPASI and GPPGA reached 1. During the treatment, the patient developed anaphylactic adverse reactions, which were improved following the injection of betamethasone, antihistamine and symptomatic therapy. Conclusion Spesolimab is an effective and safe agent for the treatment of generalized pustular psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: Generalized pustular psoriasis (GPP) is a rare and chronic, debilitating skin condition characterized, in its acute flare phase, by clinically severe and potentially life-threatening systemic manifestations. Data on GPP are still scanty, particularly in Europe and at a national level. The aim of this study was to provide expert indications on several disease-related and patient-related aspects of GPP, with specific focus to the Italian context. Methods: We conducted an iterative eDelphi study following the recommended criteria for reporting methods and results. After a thorough bibliographic review aimed to identify unknown or controversial issues in GPP, the following areas were investigated through a few specific questions/statements for each area: (1) disease epidemiology; (2) disease characteristics, with specific interest toward GPP flares; (3) diagnosis and diagnostic delay; (4) GPP treatment; (5) GPP patient journey and use of healthcare resources in Italy; (6) unmet needs and quality of life. An Executive Board of 9 principal investigators revised and approved the topics to be examined and overviewed the whole project. A total of 35 experts from different Italian areas, including 34 board-certified Italian dermatologists and 1 representative of patients' associations, took part in the study. Results: A high agreement in responses from Italian experts emerged during two eDelphi iterations on – among several other aspects – GPP prevalence and incidence in Italy, use of European Rare and Severe Psoriasis Expert Network diagnostic criteria, flare frequency and duration, best diagnostic and care pathway, and main unmet needs of Italian patients. On the other hand, a broad spectrum of treatments (of different drug classes) was reported both in the acute and chronic phases of GPP, and no consensus on the issue was thus achieved. Conclusions: Consensus findings from this Delphi study of GPP experts may be useful to fill gaps of knowledge and improve awareness of this rare disease, as well as to help clinical and public health management of GPP in Italy. [ABSTRACT FROM AUTHOR]

Generalized Pustular Psoriasis (GPP) is a dermatological autoinflammatory disease that rarely occurs in children and is associated with complex genetic factors. GPP pathogenesis has been associated with mutations in IL36RN gene, which encodes an interleukin-36 receptor antagonist. GPP usually occurs without a history of psoriasis in the patients or their family members. This case report describes the clinical course of a 3-year-old toddler with GPP. The diagnosis of GPP was confirmed through a comprehensive series of examinations, and genetic testing revealed an IL36RN mutation, providing further insight into the genetic basis of the condition. This case highlights the importance of a genetic perspective for diagnosing GPP, particularly in children. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a disease that presents with fever and multiple sterile pustules on flushed skin all over the body. GPP should be considered as systemic inflammatory response syndrome (SIRS), and is occasionally associated with respiratory failure. We encountered a case of GPP with organizing pneumonia (OP) during treatment for rheumatoid arthritis (RA). A 74-year-old Japanese woman with RA developed fever and erythema with small pustules on the trunk and extremities. She was diagnosed as GPP and admitted to our hospital. During the clinical course, she suffered hypoxia from OP. Although RA and OP are known to coexist, GPP and OP share the involvement of cytokines such as interleukin 8 in the pathogenesis. These cytokines are therefore also involved in the complications of GPP and OP. [ABSTRACT FROM AUTHOR]

BackgroundGeneralized pustular psoriasis (GPP) is a severe type of psoriasis. The current treatment primarily relies on corticosteroids and immunosuppressants. In recent years, biologics have been increasingly utilized in the treatment of this disease, and have demonstrated good clinical efficacy. However, children and adolescents are primarily treated with immunosuppressants, which have limited clinical application due to the serious side effects they may cause. At the same time, the effectiveness of current treatments is unsatisfactory. Secukinumab has been widely reported to be effective and safe in treating this disease. However, there are still insufficient data on its use in treating GPP in children.ObjectiveTo conduct a systematic review of the existing literature on the use of secukinumab for treating generalized pustular psoriasis in children and adolescents, and to evaluate its clinical effectiveness and safety.MethodsWe conducted a systematic review of all the literature reporting on the treatment of GPP in children and adolescents with secukinumab.ResultsA total of 7 papers (46 patients) were included in this study. After 12 weeks of treatment, all 46 participants were able to achieve a GPPASI score of 90 or higher, with approximately 96% of patients achieving complete clearing of the lesions (GPPASI 100 or JDA0). Adverse events were reported in 8 patients, the rate of adverse reactions was approximately 17%.ConclusionThe treatment of GPP in children and adolescents with secukinumab has a rapid onset of action and a high safety profile. However, the results of the literature may be influenced by publication bias.

Generalized pustular psoriasis (GPP) is a chronic, rare, and potentially life-threatening inflammatory disease, characterized by the rapid and widespread eruption of small, sterile pustules with surrounding skin erythema. Abnormal signaling of the interleukin-36 (IL-36) pathway appears to have a central role in GPP immunopathology, and provides a rational therapeutic target. Spesolimab is a first-in-class humanized monoclonal antibody that binds specifically to the IL-36 receptor, and antagonizes IL-36 signaling. Spesolimab obtained regulatory approval in the United States (US) in September 2022 for use in the treatment of GPP flares in adults, and was subsequently approved for GPP flare treatment in many other countries across the world. Recently, regulatory approval was granted for subcutaneous dosing of spesolimab for treatment of GPP when not experiencing a flare. Here, we review data from two key clinical trials that supported the initial US regulatory approval; namely, the phase 1 proof-of-concept trial (ClinicalTrials.gov ID, NCT02978690), and Effisayil™ 1 (NCT03782792), which remains the largest and only randomized clinical trial in patients experiencing GPP flares published to date. In the phase 1 proof-of-concept trial, a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score of 0 or 1 (clear or almost clear skin) was attained in 5/7 (71%) patients by week 1 and in all 7 patients by week 4; and the mean percent improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score from baseline was 59.0% at week 1, 73.2% at week 2, and 79.8% at week 4. In Effisayil™ 1, a GPPGA pustulation subscore of 0 (no visible pustules) was achieved in 19/35 (54%) patients receiving spesolimab at the end of week 1, versus 1/18 (6%) receiving placebo (difference, 49 percentage points; 95% confidence interval [CI], 21 to 67; P

Joseph F Merola,1,&ast; Ahmad Z Amin2,&ast; 1Brigham and Women’s Hospital, Boston, Massachusetts, USA; 2Northwestern University Feinberg, School of Medicine, Chicago, Illinois, USA&ast;These authors contributed equally to this workCorrespondence: Dr Joseph F Merola, Email jfmerola@bwh.harvard.eduAbstract: Generalized pustular psoriasis (GPP) is the most severe form of pustular psoriasis and affects large areas of the body. GPP is a rare disease, and has a variable presentation; thus, its diagnosis is challenging. The onset of symptoms is rapid, with the appearance of painful skin erythema, followed by the widespread eruption of sterile pustules. Acute GPP (called a flare) is often accompanied by systemic symptoms, including high fever, pain in skin lesions, malaise, and fatigue. Approximately half of GPP flares require hospitalization, with an average inpatient duration of 10– 14 days. GPP prevalence estimates range from approximately 2– 124 cases per million persons, with a female predominance. The most common age of onset of GPP is 40– 60 years, although cases have been described in younger adults and children. GPP affects every aspect of patients’ lives and has a high physical and psycho-social impact. Recent research on the interleukin-36 pathway associated with GPP led to the development of a GPP-specific treatment, spesolimab, which was approved by the US FDA in September 2022. This podcast explores the clinical presentation, disease course, and burden of disease in GPP, including differential diagnosis and common triggers of an acute flare.Keywords: generalized pustular psoriasis, interleukin-36 pathway, clinical presentation, disease burden, diagnosis

Abstract Generalized pustular psoriasis (GPP) is a chronic, rare, and potentially life-threatening disease. There is limited understanding of patient characteristics in GPP and their correlation with disease progression or healthcare resource utilization. Our review aims to examine real-world evidence on these characteristics and the associated disease burden as related to economic and quality of life factors. Results showed that most patients with GPP experienced flares once a year, lasting from 2 weeks to 3 months, with > 80% of patients having residual disease post-flare, with/without treatment, indicating the long-term nature of GPP. The impact of GPP on patients’ daily activities was significant, even in the absence of a flare. GPP adversely affected mental health, and anxiety and depression were reported regularly. Patients with GPP had more comorbidities, were prescribed more medication, and had more inpatient and outpatient visits than in matched plaque psoriasis or general population cohorts. Improving the education of healthcare providers in diagnosing GPP, defining disease flares, and managing the disease, as well as making globally accepted clinical guidelines for GPP treatment available, could help to reduce the burden on patients with GPP. Effective therapies that control and prevent GPP flares and manage chronic disease are needed.

Generalized pustular psoriasis (GPP) is a rare chronic inflammatory pustular dermatosis that presents as painful erythema with sterile pustules on nonacral skin. No unified standard and guideline for the treatment of GPP has been established. Several biologics have been tried for GPP, with varying success. Acrodermatitis continua of Hallopeau (ACH) is a very rare disabling variant of pustular psoriasis characterized by sterile pustules on the fingers and toes, including the nail bed. Comparatively, treating ACH is highly challenging due to its commonly therapy-resistant disease course. The pathogenic role of IL-36 signaling axis has been currently identified in GPP development. Spesolimab, the first anti-interleukin-36 receptor biologic, has been approved for treating GPP flares and shown promising results. In view of a shared pathogenesis between GPP and ACH, specolimab may be an effective treatment for ACH. Currently, there is no case and clinical trial data exist on this condition. Therefore, this case was aim to describe real-world experience of spesolimab use in ACH coexisting with GPP. We report an Asian patient with a 16-year-history of GPP and ACH with marked pustulosis on the nail bed and onychodystrophy. He received conventional systemic regimen acitretin, cyclosporine and biologics adalimumab and secukinumab, but experienced relapse for skin lesions and refractory for nail lesions. He was then treated with a single dose of spesolimab in combination with secukinumab, which resulted in skin clearance and nearly complete resolution of nail lesions over a 32-week period. Our observation suggests that spesolimab should be considered for the treatment of ACH, especially in the patients with intractable nail lesions and concomitant GPP. [ABSTRACT FROM AUTHOR]