Generalized Pustular Psoriasis Patients Research Articles

Rapid and sustained resolution in generalized pustular psoriasis with IL-17A inhibitors required high adherence: a 96-week analysis in a real-life setting.

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. 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). Using the as-observed (AO) method, 87% and 67% of patients treated with secukinumab or ixekizumab achieved GPPASI 90and 100responses, 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. 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.

Spesolimab Use for Generalized Pustular Psoriasis Flare Prevention in Patients with Concomitant Plaque Psoriasis: Results from the Effisayil 2 Trial

Introduction &amp; Objectives: Generalized pustular psoriasis (GPP) is a chronic inflammatory, potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is approved to treat GPP flares in adults. Effisayil 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous spesolimab in preventing GPP flares. Here, we report the effect of spesolimab versus placebo on Target Plaque Severity Score (TPSS) in patients with concomitant plaque psoriasis (PsO) in Effisayil 2.&#x0D; Materials &amp; Methods: Eligible patients with a history of GPP were randomized (1:1:1:1) to high-dose spesolimab (loading dose 600 mg, maintenance dose 300 mg every 4 weeks), medium-dose spesolimab (loading: 600 mg, maintenance: 300 mg every 12 weeks), low-dose spesolimab (loading: 300 mg, maintenance: 150 mg every 12 weeks), or placebo for 48 weeks. One PsO lesion of ≥9 cm2 with TPSS total score ≥5 and induration sub-score ≥2 was selected by the investigator at baseline for each participant. Severity of erythema, scaling, and induration (plaque thickness) of the target lesion was assessed at baseline and subsequent visits on a 5-point scale (0, none to 4, very marked), with the summation of the 3 subscores representing the TPSS total score (0-12).&#x0D; Results: TPSS was measured in the 33/123 (27%) patients with PsO in the trial (9 placebo, 10 low-dose, 7 medium-dose, 7 high-dose). Mean TPSS total score was 4.2 in placebo and 4.6 in spesolimab-treated patients at baseline. By Week 4, mean TPSS remained similar in both groups (placebo, 4.3; spesolimab, 4.6). By Week 16, mean TPSS in the placebo group increased to 4.4 and decreased to 3.6 in spesolimab-treated patients. Mean TPSS total scores at Week 48 for both groups were below baseline (placebo, 3.3; spesolimab, 3.8). The number of patients with TPSS data declined in both groups over time due to GPP flare and/or early discontinuation.&#x0D; Conclusion: Low baseline TPSS scores observed in this subpopulation of 33 GPP patients with concomitant PsO suggest that concomitant PsO plaque characteristics in GPP are generally mild to moderate. TPSS scores remained low and consistent throughout the trial in both dosing groups and decreases in TPSS score by Week 16 (spesolimab-treated) and Week 48 (both groups) compared to baseline were observed.

Successful Treatment of Generalized Pustular Psoriasis during Pregnancy by Cyclosporin and Etanercept: Own Experience and Review of Literature

Psoriasis is a common inflammatory skin disease affecting about 2% of the population. Generalized pustular psoriasis (GPP) is a rare variant of this disease, and it can be life-threatening for a pregnant woman and fetus. Medication during pregnancy can be challenging since many drugs can cause marked adverse effects for a fetus or newborn baby. Because controlled studies are difficult to perform, the knowledge grows slowly, e.g., from case reports. Here we describe a review of past and present treatments for GPP patients with a special reference to pregnancy and our experience on two GPP cases treated with cyclosporin and etanercept during pregnancy with successful outcomes of infants.

Better efficacy, lower recurrence rate and decreased CD8+TRM with guselkumab treatment for generalized pustular psoriasis: A prospective cohort study from China

Generalized pustular psoriasis (GPP) is a severe and uncommon form of psoriasis, for which treatment options are limited. There is an urgent need to expand the treatment options for GPP. Currently, adalimumab, secukinumab, and guselkumab are considered effective for GPP, but there is a lack of prospective direct comparative studies on their efficacy for GPP. We conducted a prospective, single-center, observational study on 50 GPP patients to compare the efficacy, safety, and recurrence rates of these three biologics. Adalimumab, secukinumab, and guselkumab resulted in varying degrees of improvement in patients with GPP, but guselkumab exhibited superior efficacy and a lower recurrence rate than the other two drugs. This enhanced response may be attributed to the significant reduction in CD8+ tissue-resident memory T cells within GPP lesions caused by guselkumab.

A US Claims Database Analysis Estimating Risk of All-Cause Mortality in Patients with Generalized Pustular Psoriasis

Introduction: Generalized pustular psoriasis (GPP) is a rare, chronic, neutrophilic skin disease characterized by recurring flares of widespread erythema, edema, coalescing pustules, and possible systemic symptoms. GPP flares may require hospitalization and can be life-threatening. There are limited data describing the mortality burden of GPP in the US. This study compared all-cause mortality among patients with GPP with matched patients with plaque psoriasis (PsO), and the general population without GPP or PsO.&#x0D; Methods: Inovalon Insights real-world claims data were used to identify 5 cohorts (All GPP, Comorbid GPP+PsO, GPP Only, PsO Only, General Population) based on the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes from Jan 1, 2016, to Dec 31, 2019. GPP Only, PsO Only, and Comorbid GPP+PsO were mutually exclusive. All GPP included GPP Only (excluding PsO) and Comorbid GPP+PsO. General Population comprised qualifying patients without a medical claim for GPP or PsO during pre- and post-index periods. All-cause mortality was assessed both 365 days post-index diagnosis and during a maximum follow-up period (until study period ended or patient experienced an event). Greedy caliper propensity score matching was used to match GPP patients 1:2 to PsO and General Population using index year, age, gender, insurance type, region, and Charlson Comorbidity Index (CCI). All-cause mortality risk was assessed using Cox proportional hazard models.&#x0D; Results: Patients were primarily female and commercially insured. The GPP Only cohort was older at index and had higher CCI scores than PsO Only and General Population (p&lt;0.001), highlighting the higher severity of GPP. At 365 days follow-up, All GPP had a significantly higher mortality risk than General Population (HR 4.93, 95% CI 2.24-10.88) and PsO Only (HR 2.31, 95% CI 1.32-4.04). GPP+PsO had a significantly higher mortality risk than PsO Only (HR 2.67, 95% CI 1.15-6.20). At 365 days follow-up, GPP Only had a numerically higher mortality risk than PsO; risk was significantly higher at the later timepoint. At maximum follow-up, the mortality risk for All GPP was almost 4 times higher than General Population (HR 3.98, 95% CI 2.92-5.43) and 1.5 times higher than PsO Only (HR 1.49, 95% CI 1.20-1.85). In GPP+PsO and GPP Only, the mortality risk was almost 1.5 times the risk of PsO Only (HR 1.41, 95% CI 1.05-1.90; HR 1.49, 95% CI 1.10-2.03); all comparisons at maximum follow-up were statistically significant.&#x0D; Conclusion: This study characterizing all-cause mortality in patients with GPP demonstrated a higher risk of mortality in GPP than matched PsO and General Population cohorts. These results fill a gap in the existing literature and reinforce the need for awareness of the mortality burden and the comorbidity burden in GPP

Expression of interleukin-36 receptor antagonist in a patient with generalized pustular psoriasis harboring the p.Pro82Leu variant in the IL36RN gene.

It has recently been revealed that mutation of the IL36RN gene contributes to the development of generalized pustular psoriasis (GPP). The IL36RN gene encodes interleukin (IL)-36 receptor antagonist (IL-36Ra), which has antagonistic roles against IL-36α, -36β, and -36γ. Previously, sanger sequencing performed in 62 Chinese GPP patients to identify IL36RN mutations revealed a new variant, c.245C>T (p.Pro82Leu), in a single heterozygous state in a patient with adult-onset GPP with psoriasis vulgaris. Since this p.Pro82Leu variant was not found in the psoriasis vulgaris or control groups in their study, they speculated that this variant might lead to exacerbated inflammatory responses. Meanwhile, Sorting Intolerant From Tolerant and PolyPhen-2, pathogenicity prediction tools, predict this variant as tolerated and benign. To date, its pathogenicity is unknown. We experienced a patient with GPP harboring the p.Pro82Leu variant, and investigated mRNA and protein expressions of IL-36Ra. Polymerase chain reaction conducted on hair follicle samples obtained from the scalp of the patient with GPP harboring the p.Pro82Leu using primers to detect mRNA of exons 2 and 5 in IL36RN demonstrated mRNA expression of IL36RN. Immunohistochemical staining revealed IL-36Ra expression in the keratinocytes of the patient with GPP harboring the p.Pro82Leu as in those of a GPP patient without the mutation (positive control). Furthermore, quantitative analysis of the immunofluorescent staining by ImageJ revealed that the expression level of IL-36Ra in the keratinocytes of the patient with GPP harboring p.Pro82Leu was higher than that in the healthy control and not lower than that in the GPP patients without the mutation. Our results indicate no aberrant splicing in this variant. In addition, according to the 1000 Genomes Project, this variant could be a founder mutation. Considering these factors together, this variant is unlikely to be associated with the development of GPP.

Clinical characteristics and heterogeneity of generalized pustular psoriasis: A comparative study in a large retrospective cohort.

Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening skin disease and the clinical heterogeneity of which is largely unknown. Retrospective cohort analysis was conducted on hospitalized GPP patients between January 2010 and November 2022. A total of 416 patients with GPP and psoriasis vulgaris (PV) respectively were included, matched 1:1 by sex and age. The heterogeneity of GPP was stratified by PV history and age. Compared with PV, GPP was significantly associated with prolonged hospitalization (11.7 vs. 10.3 day, p < 0.001), elevated neutrophil lymphocyte ratio (NLR) (5.93 vs. 2.44, p < 0.001) and anemia (13.9% vs. 1.2%, p < 0.001). Moreover, GPP alone (without PV history) was a relatively severer subtype with higher temperature (37.6°C vs. 38.0°C, p = 0.002) and skin infections (5.2% vs. 11.4%, p = 0.019) than GPP with PV. For patients across different age, compared with juvenile patients, clinical features support a severer phenotype in middle-aged, including higher incidence of anaemia (7.5% vs. 16.0%, p = 0.023) and NLR score (3.83 vs. 6.88, p < 0.001). Interleukin-6 (r = 0.59), high density lipoprotein cholesterol (r = -0.56), albumin (r = -0.53) and C-reactive protein-to-albumin ratio (r = 0.49) were the most relevant markers of severity in GPP alone, GPP with PV, juvenile and middle-aged GPP, respectively. This retrospective cohort suggests that GPP is highly heterogeneous and GPP alone and middle-aged GPP exhibit severe disease phenotypes. More attention on the heterogeneity of this severe disease is warranted to meet the unmet needs and promote the individualized management of GPP.

A narrative review of studies assessing the quality of life in patients with generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a clinical entity distinct from psoriasis, associated with a poor clinical prognosis, often resulting in severe systemic complications and mortality. The relapsing nature of the disease with recurrent or intermittent flares imposes a significant burden on patients' quality of life (QoL). Although inadequately studied, QoL data in GPP patients has been a recent point of investigation. We conducted a literature search on PubMed/MEDLINE using the following search terms: 'generalized pustular psoriasis' OR 'pustular psoriasis' AND 'quality of life'. We identified 12 relevant articles that provide insight into the large impact of GPP on the QoL of patients, the burden of the disease and the treatment, and the success of new treatment options in making a clinically important difference to QoL. This review illustrates a need for routine assessment of the QoL in interventional clinical trials for GPP and during physician encounters. This information can help guide clinicians on how to tailor the treatment approach from the patient's perspective or illustrate whether new therapies offer meaningful benefits to patient care as we enter an era of exciting new treatments for this challenging condition.

Clinical profile of patients with acute generalized pustular psoriasis with and without IL36RN mutations in multi-ethnic Johor Bahru, Malaysia.

Generalized Pustular psoriasis (GPP), a rare and potentially life-threatening auto-inflammatory disease, is associated with IL36RN mutations. Here, we analyse the prevalence of IL36RN mutations in our multi-ethnic GPP cohort and assess differences in the clinical profile of patients with (IL36RN-positive) and without (IL36RN-negative) mutations. IL36RN mutations were present in 17.7% of 137 GPP patients (29.7% of Chinese cases, 17.3% of Malay cases, but 0% of Indian patients). 92% of these individuals carried the c.115 + 6T > C mutation. Male: female ratio was 1:2.3. Females predominate in both groups with no significant difference between IL36RN-positive and IL36RN-negative individuals. The overall mean age (±SD) at disease onset for GPP was 37.6 ± 17.2 years, but disease onset was significantly earlier in IL36RN-positive vs IL36RN-negative cases (mean age:30.6 ± 18.92 vs. 39.2 ± 16.49 years, p=0.027). IL36RN-positive patients were less likely to have associated plaque psoriasis (52.4% vs. 83.5%, p-value=0.002). There was no difference in the common clinical and laboratory manifestations or triggers of GPP between IL36RN-positive and -negative patients, except for geographic tongue which was significantly more common in IL36RN-positive patients (41.7% vs. 11.9%, p-value=0.002). Annual flare rate was significantly higher in IL36RN-positive compared to IL36RN-negative (mean ± SD of 1.92 ± 1.32 vs. 1.46 ± 0.90, p=0.041) cases. However, no significant difference in the rate of hospitalization and length of hospital stay was observed between the two groups. These observations demonstrate that IL36RN disease alleles occur with varying frequencies among Asian populations and are associated with a severe, early-onset clinical phenotype.

Translated article] Epidemiology and Geographic Distribution of Generalized Pustular Psoriasis in Spain: A National Population-Based Study of Hospital Admissions from 2016 to 2020

IntroductionLittle has been published on the epidemiology of generalized pustular psoriasis (GPP). The aim of this study was to describe and analyze the geographic distribution of hospital admissions for GPP in Spain. MethodsWe performed a cross-sectional study using the hospital discharge database of the Spanish Basic Minimum Data Set (CMBD), which is a mandatory data set of all admissions to public hospitals in the country. We included patients with a primary diagnosis of psoriasis or GPP at discharge for the period 2016–2020. We performed a descriptive analysis of clinical and sociodemographic characteristics of patients admitted with GPP, a spatial analysis at the province level assessing the presence of geographic heterogeneity and a GPP disease map. ResultsWe detected 949 diagnoses of psoriasis and 744 primary diagnoses of GPP. Mean age of patients admitted with GPP was 62.2 years. Intensive care unit admissions were ordered for 6.1% of patients and 4.8% died. The overall incidence rate of newly hospitalized GPP patients during the study period was 3.18 cases per 1,000,000 person-years. The geographic distribution varied widely, with higher rates observed in the north-west of the country. ConclusionsWe describe the characteristics of GPP hospitalized patients in Spain and provide the first disease map for the country. The findings could help guide future research and suggest the possibility of genetic or environmental factors driving geographic differences.

Serum levels of angiogenesis-related factors in patients with psoriasis.

Psoriasis is characterized by increased dermal vascularity, indicating that aberrant angiogenesis is associated with the pathogenesis of psoriasis. Data on angiogenesis-related factors in psoriasis patients are limited. We explored serum levels of angiogenesis-related factors in patients with psoriasis, and investigated their association with clinical severity and laboratory data. Psoriasis patients visiting our hospital from April 2013 to April 2018 and healthy controls were included in this study. Serum levels of angiopoietin-1, fibroblast growth factor (FGF)-basic, epidermal growth factor (EGF), platelet endothelial cell adhesion molecule (PECAM)-1, placental growth factor, and vascular endothelial growth factor (VEGF) were measured by LEGENDplex. Serum samples obtained from 10 healthy controls, 18 patients with psoriasis vulgaris (PsV), 24 patients with psoriatic arthritis (PsA), and 13 patients with generalized pustular psoriasis (GPP) were analyzed. The serum angiopoietin-1 level was elevated in the PsV, PsA, and GPP patients. GPP patients had a higher serum VEGF level than healthy controls. In contrast, serum levels of EGF and PECAM-1 were lower in the PsV, PsA, and GPP patients than in healthy controls. The serum FGF-basic level was lower in the PsA and GPP patients than in healthy controls. Serum levels of FGF-basic in PsA and GPP patients, PECAM-1 in PsA patients, and VEGF in GPP patients became closer to the respective levels in healthy controls after systemic therapy. The serum FGF-basic level was positively correlated with the psoriasis area and severity index and the number of circulating eosinophils in GPP patients. The serum VEGF level was correlated positively with the serum C-reactive protein (CRP) level and erythrocyte sedimentation rate, and negatively with the serum albumin level in GPP patients. In conclusion, our exploratory study revealed that psoriasis affects serum levels of certain angiogenesis-related factors. Some of these factors could be biomarkers of treatment outcomes, clinical severity, and systemic inflammation.

32339 Expression of interleukin 36 receptor antagonist in a patient with generalized pustular psoriasis harboring the p.Pro82Leu variant in the IL36RN gene

Background: Mutation of the IL36RN gene contributes to the development of generalized pustular psoriasis (GPP). The IL36RN gene encodes interleukin (IL)-36 receptor antagonist (IL-36Ra), which has antagonistic roles against IL-36. Li et al. performed sanger sequencing to identify IL36RN mutations in 62 Chinese GPP patients, and reported a new variant, c.245C>T (p.Pro82Leu) in a patient with GPP. Since this p.Pro82Leu variant was not found in the psoriasis vulgaris and control groups in their study, they speculated that this variant might lead to exacerbated inflammatory responses.

LB917 Treatment patterns and unmet needs of generalized pustular psoriasis (GPP) patients with flares

Background:Generalized pustular psoriasis (GPP) is a rare disease with little known about the treatment of flares. Objective:To characterize treatment patterns for GPP flares documented in their medical record. Methods:This retrospective descriptive study included adult GPP patients (ICD-10 codes L40.1) identified in the Optum® de-identified electronic health record (EHR) data from 7 July 2015-30 June 2020. The index GPP diagnosis was the first occurrence in the EHR with no history of GPP for at six months prior.

Identifying patients with deteriorating generalized pustular psoriasis: Development of a prediction model.

Generalized pustular psoriasis (GPP) is a life-threatening condition; however, little is known about the factors that can predict GPP patients manifesting a deteriorating course. To investigate the demographics and clinical features of adult inpatient GPP and propose a prediction model for detecting fatal GPP (fGPP) and GPP requiring intensive care unit admission (iGPP) patients, a nationwide population-based retrospective cohort study was conducted. The adult inpatients with GPP from January 2007 to December 2020 were assessed. The 800 cases were aged 51.0 years (median [interquartile range, 37.0-64.0]). Overall, 21 iGPP (64.0 years [54.0-77.0]) and 17 fGPP (75.0 years [68.0-77.0]) cases were identified as deteriorating GPP. Renal disease (odds ratio [OR], 7.31), myocardial infarction history (OR, 4.29), liver disease (OR, 2.82), and diabetes mellitus (OR, 2.34) were identified as predictors for iGPP. For fGPP, myocardial infarction history (OR, 5.10) and psoriasis history (OR, 3.13) were established as predictors. A prediction model with scores ranging 0-11 points showed a reliable diagnostic value in detecting deteriorating GPP (area under the curve=0.75 for iGPP and 0.83 for fGPP). In conclusion, this study provides the clinical features of deteriorating GPP. A prediction model may help physicians to identify patients with deteriorating GPP.

Sociodemographic, clinical, laboratory, treatment and prognostic characteristics of 156 generalized pustular psoriasis patients in Turkey: a multicentre case series.

Generalized pustular psoriasis (GPP) is a rare and severe inflammatory disease characterized by widespread and superficial sterile pustules on an erythematous background. This multicentre study aimed to determine the clinical profile and course in a large cohort of patients with GPP. One hundred and fifty-six GPP patients (mean age, 44.2 ± 18.7 years) who met the diagnostic criteria of the European Consensus Report of GPP were included in the study. Sociodemographic characteristics, quality of life, triggering factors of the disease, clinical, laboratory, treatment and prognostic features were evaluated. 61.5% of the patients were female. The rate of working at or below the minimum wage (≤$332.5/month) was 44.9%. Drugs (36.5%) were the most common trigger. While hypocalcaemia (35.7%) was the most important cause of GPP during pregnancy, systemic steroid withdrawal (20%) was the most frequently reported trigger for infantile/juvenile and mixed-type GPP (15%) (P < 0.05). Acute GPP (53.8%) was the most common clinic. Nails were affected in 43.6% of patients, and subungual yellow spots (28.2%) were the most common change. In annular GPP, fever (P < 0.001) and relapse frequency (P = 0.006) were lower than other subtypes, and the number of hospitalizations (P = 0.002) was lower than acute GPP. GPP appeared at a later age in those with a history of psoriasis (P = 0.045). DLQI score (P = 0.049) and joint involvement (P = 0.016) were also higher in this group. Infantile/juvenile GPP was observed in 16.02% of all patients, and arthritis was lower in this group (24.4 vs. 16%). GPP of pregnancy had the worst prognosis due to abortion observed in three patients. Recent advances in treatment have improved mortality associated with GPP, but abortion remains a significant complication. Although TNF-α inhibitors have proven efficacy in GPP, they can also trigger the disease. Mixed-type GPP is more similar to acute GPP than annular GPP with systemic manifestations and course.

Profiling and multivariate analysis of serum cytokines in patients with generalized pustular psoriasis

Introduction: Generalized pustular psoriasis (GPP) is a chronic autoinflammatory disease characterized by fever, erythema, and sterile pustules occurring over large areas of the skin. The immunopathogenesis of GPP remains poorly understood. We aimed to profile serum cytokine levels in patients with GPP and analyze treatment-associated changes in cytokine levels. Methods: Twenty-four patients who were diagnosed with GPP and received drug treatment, together with 28 unaffected controls, were recruited in this study. Levels of 27 cytokines in serum samples from pre- and post-treated patients as well as unaffected controls were assessed using a Bio-Plex multiplex immunoassay. Multivariate analysis of cytokine levels and clinical parameters was conducted. Results: Serum levels of interleukins interleukin (IL)-1β, IL-1Ra, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), IFN-γ-induced protein 10 (IP-10), monocyte chemoattractant protein-1, tumor necrosis factor-α, and vascular endothelial growth factor were significantly elevated (p &lt; .05) in patients with GPP compared with controls. Serum levels of IL-6, G-CSF, IL-8, IFN-γ, IL1-Ra, IL-10, IL-13, and IL-1β were correlated with GPP severity (r &gt; 0.4, p &lt; .001). Following treatment, serum levels of IL-6, IL-7, IL-12, IFN-γ, IL-1β, IL-4, IL-8, IL-10, IL-13, G-CSF, and IP-10 were significantly decreased (p &lt; .05) compared with pretreatment levels. Among these cytokines, levels of IL-6, IL-7, IL-8, IL-12, IL-13, and IP-10 were reduced to normal levels. Conclusion: GPP patients exhibited markedly elevated levels of cytokines and chemokines involved in both type 1 and type 2 immune responses, suggesting hypercytokinemia occurs in GPP patients. IL-6 showed the strongest correlation with GPP disease severity and other clinical parameters such as CRP level and fever, thus representing an index for GPP severity. Our data comprehensively documented the cytokine profiles of GPP patients and may provide insights into GPP pathogenesis.

Healthcare Resource Utilization and Baseline Characteristics of Patients With Generalized Pustular Psoriasis: Real-World Results From a Large US Database of Multiple Commercial Medical Insurers

Background: Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disease with high unmet clinical need. The introduction of a GPP-specific International Classification of Diseases, 10th Revision (ICD-10), code has made it possible to generate a more accurate GPP patient profile. Objectives: To describe the characteristics and compare the patient profile and burden of disease of patients with GPP with patients with plaque psoriasis. Methods: A retrospective study was conducted using a US administrative claims database, the IBM® MarketScan® Research Database. The study took place between October 1, 2015, and September 30, 2018. Patients with at least 1 inpatient or 2 outpatient L40.1 (GPP) or L40.0 (psoriasis vulgaris) diagnostic codes were included for analysis. Outcome measures included descriptions of comorbidities, medication use, and healthcare resource utilization (HCRU) among GPP, plaque psoriasis, and general population (matched to those with GPP) cohorts. Results: Patients with GPP had more baseline comorbidities than those with plaque psoriasis and the matched cohort, including psoriatic arthritis (20.6% vs 6.4% and &lt;0.1%) and hyperlipidemia (20.4% vs 16.3% and 11.8%). Patients with GPP also had greater medication use and higher HCRU than those with plaque psoriasis and the matched cohort. Conclusion: Patients with GPP generally experience more comorbidities, with higher HCRU, than patients with plaque psoriasis. Although the large dataset permitted identification of GPP patients with longitudinal follow-up, the lack of a validation algorithm for GPP is a limitation and a potential area for future research.

Metabolic syndrome‐related SNPs in HLA and TNF7L2 may be risk factors for generalized pustular psoriasis in Chinese Han population

BackgroundGeneralized pustular psoriasis (GPP) is a rare and severe type of psoriasis. Previous studies have reported that metabolic syndrome and its components have been associated with psoriasis.ObjectiveTo investigate the association of metabolic syndrome‐related single‐nucleotide polymorphisms (SNPs) and GPP in Chinese Han population.Materials and MethodsOne hundred and thirty‐six (136) GPP patients and 965 healthy controls were recruited in the study. Approximately, 4 ml peripheral venous blood was collected from each participant. After collection, second‐generation sequencing was used to detect genetic polymorphism of 15 SNPs. The plink 1.07 software package was used for statistical analysis.ResultsRs805303 (p = 0.01, OR = 0.70) and rs3177928 (p = 3.18E−07, OR = 2.66) in HLA were significantly different between the two groups. Moreover, rs4506565 (p = 1.41E−03, OR = 2.72) and rs7901695 (p = 9.39E−04, OR = 2.82) in TCF7L2 were significantly associated with GPP in patients without a previous history of PsV. Genotype analysis of rs4506565 and rs7901695 showed that under the recessive model, genotype frequencies of rs4506565 (p = 0.00, OR = 18.52) and rs7901695 (p = 0.00, OR = 18.44) were significantly different between GPP patients and healthy controls.ConclusionRs805303 and rs3177928 in HLA may increase the risk of GPP in the Chinese Han population. TCF7L2 may be a risk factor for GPP in patients without a previous history of PsV.

Economic burden of generalized pustular psoriasis and palmoplantar pustulosis in the United States

Objective To estimate healthcare resource utilization (HCRU) and economic burden of generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP) in a commercially insured population the United States (US). Methods Adult patients with a GPP or PPP diagnosis were identified between April 1, 2016 and August 1, 2019 in the IQVIA PharMetrics Plus database. Patients required continuous enrollment in medical and pharmacy benefits 6 months before and ≥2 months after the index diagnosis. GPP and PPP cohorts were exactly matched 1:3 on demographics and index date to a plaque psoriasis and a control cohort of the general population. All-cause HCRU and cost measures (direct medical and pharmacy) were reported as per patient per month (PPPM). Generalized linear models estimated adjusted cost ratios between matched cohorts, controlling for comorbidities. Results HCRU was high among GPP and PPP patients. Rates of inpatient visits were 4 times higher in GPP patients and 2 times higher in PPP patients compared to their matched cohorts. GPP patients experienced significantly higher total healthcare costs compared to matched cohorts (GPP vs plaque psoriasis: cost ratio 1.36, 95% confidence interval (1.22, 1.50); GPP vs control: 5.58 (3.73, 8.36)). PPP patients had significantly higher total healthcare costs compared to the general population (4.11 (3.31, 5.11)), while costs were comparable to plaque psoriasis patients (1.06 (0.97, 1.16)). Conclusions GPP and PPP patients have significant economic burden due to higher direct medical and pharmacy costs. Further investigation is needed to better understand the drivers of economic burden in patients with GPP and PPP, and how HCRU and costs are impacted by disease severity.

Excellent response to secukinumab in an infant with severe generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) represents the rarest form of psoriasis, which may be potentially fatal. In the last decade, (likely) pathogenic variants in the IL36RN, CARD14 and AP1S3 genes have been associated with monogenic GPP forms. Despite these advances, the genetic basis of most patients with GPP remains unidentified. Treatment of GPP patients is often difficult, with no consensus about the best available options to date. We report herein an infant with severe GPP in whom the disease started at the age of 2months. Genetic investigations identified a heterozygous pathogenic variant in the IL36RN gene associated with a heterozygous variant of uncertain significance in the CARD14 gene. After previous treatment failures with acitretin, cyclosporin and anakinra, treatment with the interleukin-17 antagonist secukinumab resulted in a dramatic and prompt positive response that persisted at 12-month follow up. According to our experience, we believe secukinumab can be an effective and safe treatment for pediatric patients with GPP even before 1year of age.