BACKGROUND Paradoxical psoriasis induced by tumor necrosis factor alpha antagonists is a rare side effect of those drugs and has similarities with and differences from classical psoriasis in clinical and pathological ...BACKGROUND Paradoxical psoriasis induced by tumor necrosis factor alpha antagonists is a rare side effect of those drugs and has similarities with and differences from classical psoriasis in clinical and pathological characteristics.Treating severe paradoxical psoriasis is challenging because the reported cases are rare,with treatment experience being only anecdotal.CASE SUMMARY We report 2 cases of paradoxical psoriasis caused by infliximab.Both cases manifested with a significant number of pustular lesions and had protracted and complicated clinical courses.In case 1,secukinumab alone could not control the eruptions,but colchicine supplementation markedly decreased disease activity.In case 2 miscellaneous medications were administered,including the systemic drug acitretin,the immunosuppressive drug cyclosporine,and the biologic agent ustekinumab.However,multiple applications of those medications failed to prevent new lesions from occurring.Both cases showed moderate-to-high antinuclear antibody titers.CONCLUSION Based on these cases,moderate-to-high anti-nuclear antibody titer seems to be a risk factor for paradoxical psoriasis.In addition,extensive pustular presentation may be a negative prognostic indicator and may portend a protracted clinical course refractory to therapy.展开更多
Generalized pustulous psoriasis is characterized by the sudden onset of diffuse erythema, with a scattering of pustules, sometimes with fever and others symptoms. It is a relatively rare disease^1. The treatment of tr...Generalized pustulous psoriasis is characterized by the sudden onset of diffuse erythema, with a scattering of pustules, sometimes with fever and others symptoms. It is a relatively rare disease^1. The treatment of traditional western medicine have various adverse drug reactions and easy to recur. Meanwhile, this report describes a 12-year-old female patient of generalized pustulous psoriasis with a satisfactory effect of traditional Chinese medicine.展开更多
To the Editor:Annular pustular psoriasis(APP),a rare variant of generalized pustular psoriasis(GPP),manifests as recurrent,ring-shaped erythematous lesions adorned with small,sterile pustules,following a subacute traj...To the Editor:Annular pustular psoriasis(APP),a rare variant of generalized pustular psoriasis(GPP),manifests as recurrent,ring-shaped erythematous lesions adorned with small,sterile pustules,following a subacute trajectory.The recurrent nature of APP substantially diminishes patient quality of life.Owing to its infrequency,unified treatment protocols remain elusive.展开更多
Background:Generalized pustular psoriasis(GPP),a rare and recurrent autoinflammatory disease,imposes a substantial burden on patients and society.Awareness of GPP in China remains limited.Methods:This cross-sectional ...Background:Generalized pustular psoriasis(GPP),a rare and recurrent autoinflammatory disease,imposes a substantial burden on patients and society.Awareness of GPP in China remains limited.Methods:This cross-sectional survey,conducted between September 2021 and May 2023 across 14 hospitals in China,included GPP patients of all ages and disease phases.Data collected encompassed demographics,clinical characteristics,economic impact,disease severity,quality of life,and treatment-related complications.Risk factors for GPP recurrence were analyzed.Results:Among 127 patients(female/male ratio=1.35:1),the mean age of disease onset was 25 years(1st quartile[Q1]–3rd quartile[Q3]:11–44 years);29.2%had experienced GPP for more than 10 years.Recurrence occurred in 75.6%of patients,and nearly half reported no identifiable triggers.Younger age at disease onset(P=0.021)and transitioning to plaque psoriasis(P=0.022)were associated with higher recurrence rates.The median diagnostic delay was 8 months(Q1–Q3:2–41 months),and 32.3%of patients reported misdiagnoses.Comorbidities were present in 53.5%of patients,whereas 51.1%experienced systemic complications during treatment.Depression and anxiety affected 84.5%and 95.6%of patients,respectively.During GPP flares,the median Dermatology Life Quality Index score was 19.0(Q1–Q3:13.0–23.5).This score showed significant differences between patients with and without systemic symptoms;it demonstrated correlations with both depression and anxiety scores.Treatment costs caused financial hardship in 55.9%of patients,underscoring the burden associated with GPP.Conclusions:The substantial disease and economic burdens among Chinese GPP patients warrant increased attention.Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.展开更多
Generalized pustular psoriasis(GPP)is a severe inflammatory cutaneous disease characterized by widespread pustules,edema,erythema,fever,and systemic inflammation.Chinese data indicate that the prevalence and incidence...Generalized pustular psoriasis(GPP)is a severe inflammatory cutaneous disease characterized by widespread pustules,edema,erythema,fever,and systemic inflammation.Chinese data indicate that the prevalence and incidence of GPP follow a bimodal age distribution,with peaks in the 0–3 year age group and the 30–39 year age group.1 In the 0–3 year age group,the prevalence was 0.927 and the incidence rate was 0.742 per 100000 population-years.1 Interleukin(IL)-36 plays an important role in GPP by activating nuclear factor-κB(NF-κB)and mitogen-activated protein kinase(MAPK)signal pathways.2 Chemokines(CXCL8,CXCL1,CXCL2,etc.),cytokines(IL-1β,tumor necrosis factor TNF-α,IL-6,IL-23,IL-17,etc.),and activated cells(e.g.,keratinocyte,neutrophils,dendritic cells,etc.)are also involved.3 Acitretin,cyclosporine,methotrexate,and etanercept were recommended as first-line treatments for children with GPP in 2012 by the American National Psoriasis Foundation.4 However,recent findings suggest that biological agents targeting IL-36,TNF-α,IL-17,IL-23,or their receptors might be more promising options than conventional drugs.5 Clinical trials and case series have also demonstrated the superiority of biological agents in adult and older pediatrics with GPP,including spesolimab,etanercept,adalimumab,secukinumab,brodalumab,and others.6 However,these biological agents,have only been approved by the FDA for children aged 4 years or older,and there is still limited data on their use in GPP patients under 4 years old.展开更多
Psoriasis is a chronic inflammatory skin condition that has a fairly wide range of clinical presentations.Plaque psoriasis,which is the most common manifestation of psoriasis,is located on one end of the spectrum,domi...Psoriasis is a chronic inflammatory skin condition that has a fairly wide range of clinical presentations.Plaque psoriasis,which is the most common manifestation of psoriasis,is located on one end of the spectrum,dominated by adaptive immune responses,whereas the rarer pustular psoriasis lies on the opposite end,dominated by innate and autoinflammatory immune responses.In recent years,genetic studies have identified six genetic variants that predispose to pustular psoriasis,and these have highlighted the role of IL-36 cytokines as central to pustular psoriasis pathogenesis.In this review,we discuss the presentation and clinical subtypes of pustular psoriasis,contribution of genetic predisposing variants,critical role of the IL-36 family of cytokines in disease pathophysiology,and treatment perspectives for pustular psoriasis.We further outline the application of appropriate mouse models for the study of pustular psoriasis and address the outstanding questions and issues related to our understanding of the mechanisms involved in pustular psoriasis.展开更多
Background： Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis （GPP） is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced ...Background： Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis （GPP） is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 （TNIP1） gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Hart population. Methods： Seventy-three patients with GPP, 67 patients with palmoplantar pustulosis （PPP）, and 476 healthy controls were collected from Chinese Hart population. Six single nucleotide polymorphisms （SNPs） of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs 17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio （OR） （including 95% confidence interval） were calculated. The haplotype analysis was conducted by Haploview software. Results： The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group （P ≤ 7.22 × 10^-3）, especially in the GPP patients without psoriasis vulgaris （PsV）. In the haplotype analysis, the most significantly different haplotype was H4： ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group （OR = 4.16, P = 4.459 × 10^-7）. However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs （P 〉 0.05）. Conclusions： Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIPI might be a susceptibility gene for GPE展开更多
Generalized pustular psoriasis(GPP)is a severe subtype of psoriasis,commonly combined with systemic inflammation.Gene mutations have been found to be associated with GPP and vary by ethnicity.Systemic treatments are u...Generalized pustular psoriasis(GPP)is a severe subtype of psoriasis,commonly combined with systemic inflammation.Gene mutations have been found to be associated with GPP and vary by ethnicity.Systemic treatments are usually required for the severity and potential complications of GPP.However,there is no common consensus in China,especially among pediatric patients,whose data are scarce.Acitretin,methotrexate,and cyclosporine are widely used in pediatrics with GPP,while the adverse effects should be highlighted.The emergence of different biological agents brings us into a new era.This article discusses the genetic background of Chinese patients and demonstrates the evidence of treatment in pediatrics with GPP.展开更多
Generalized pustular psoriasis(GPP)is a rare and life-threatening autoinflammatory skin disease characterized by recurrent and sudden episodes of widespread rashes with scattered sterile pustules.Clinical and genetic ...Generalized pustular psoriasis(GPP)is a rare and life-threatening autoinflammatory skin disease characterized by recurrent and sudden episodes of widespread rashes with scattered sterile pustules.Clinical and genetic evidence indicates that the pathogenesis of GPP both overlaps and is separate from psoriasis vulgaris(PV).Interleukin(IL)-23/IL-17 immune pathway is well known to play a critical role in the immunopathogenesis of PV,while the inflammation of GPP is more inclined to involve the innate immune response via the IL-1/IL-36-chemokine pathway.Mutations in IL36RN,CARD13,AP1S3,MPO,TNIP1,SERPINA3,and SERPINA1 have been shown to be associated with GPP,among which loss-of-function mutation in IL36RN is the dominant mutation with the highest prevalence.Recent studies have shown that interaction of the IL-36 pathway and the IL-23/IL-17 axis underlies the immunological disturbances of GPP,indicating that innate and adaptive immune responses intertwine in the pathogenesis of GPP.With this deeper understanding of the pathogenesis of GPP,treatment by biologics targeting the IL-1/IL-36 pathway appears to be promising.IL-1 inhibitors,anakinra,canakinumab,and gevokizumab have reportedly been effective in some cases.Spesolimab and imsidolimab,which are antibodies to the IL-36 receptor,are undergoing investigation in a phase II trial and showing promising results.In the present review,we illustrate the current understanding of the pathogenesis of GPP based on recent updates on the molecular genetics and immunopathology of GPP and review recent clinical trials and case reports of novel biologics in the treatment of GPP.展开更多
Objective:This study was performed to investigate the clinical characteristics of patients with generalized pustular psoriasis(GPP)in Northwest China.Methods:The clinical data of patients with GPP were retrospectively...Objective:This study was performed to investigate the clinical characteristics of patients with generalized pustular psoriasis(GPP)in Northwest China.Methods:The clinical data of patients with GPP were retrospectively collected in the Second Affiliated Hospital of Xi’an Jiaotong University from January 1,2017,to December 31,2021 and analyzed using the chi-square test and Mann-Whitney U test.Results:In total,179 hospitalized patients were included.The male:female ratio was 1.16:1.00,and the mean age at onset was 35.05±19.11 years.Psoriasis vulgaris was also present in 76.0%of patients,and a family history of psoriasis was present in 15.6%.The mean duration of hospitalization was 10.67±4.31 days,and the mean duration of flares was 29.58±24.32 days.Infections and suspected drugs were predisposing factors.A fever developed in 54.7%of patients,and pruritus developed in 70.9%.Some patients had involvement of the nails(38.0%),scalp(46.9%),and tongue(4.5%).Cardiovascular disease,hypertension,and gallbladder-related disease were common comorbidities.The efficacy of acitretin was 84.7%,that of methotrexate was 66.7%,and that of cyclosporine was 100%.Fifteen patients were treated with secukinumab or adalimumab and responded well.The mean response time was 6.34±2.91 days based on the combination treatments.The mean duration of the treatment regimen was 111.35±94.25 days,and approximately 46.6%(n=131)of patients developed recurrence.Conclusion:Our retrospective study showed that most cases of GPP were accompanied by psoriasis vulgaris and associated with fever or pruritus.Acitretin had good therapeutic efficacy,but recurrence should be noted.Biologics are increasingly becoming effective treatments,but their superiority and safety need further research.展开更多
Introduction:Generalized pustular psoriasis(GPP)is a rare life-threatening subtype of psoriasis and continues to be a therapeutic challenge.The first line therapies include acitretin,cyclosporin A,and methotrexate whi...Introduction:Generalized pustular psoriasis(GPP)is a rare life-threatening subtype of psoriasis and continues to be a therapeutic challenge.The first line therapies include acitretin,cyclosporin A,and methotrexate which have long-term side effects for children.Adalimumab has a favorable safety profile with low rates of adverse events,and has been described for successful treatment of adults with GPP in a few reports.We herein describe a 3-year-old girl with a body weight of 14.2 kg in whom adalimumab was used to successfully treat GPP.Case presentation:A 3-year-old girl with a 10-day history of systemic symptoms of fever,malaise,and the onset of studded painful pustules overlying an erythematous base on the scalp,face,neck,trunk,and bilateral extremities,affecting a body surface area of 90%.Laboratory examination results were notable for leukocytosis and elevated inflammatory markers.Biopsy confirmed the diagnosis of GPP.After failure of conventional therapies including cyclosporine and methotrexate,the patient began off-label treatment with adalimumab and achieved complete lesion clearance.During 14-month follow-up,she remains in remission on maintenance adalimumab therapy.Discussion:No consensus on the standard treatment regimen for GPP has been reached.Unfortunately,all drugs that have been reported to be effective for GPP are off-label.These treatments include systemic immunomodulators such as cyclosporine and methotrexate,systemic retinoids such as acitretin and isotretinoin,and various biologics.Our findings lend weight to the scant evidence describing the effective use of adalimumab in the treatment of pediatric GPP.Conclusion:Off-label use of adalimumab may be an effective and safe therapeutic option for GPP.展开更多
文摘BACKGROUND Paradoxical psoriasis induced by tumor necrosis factor alpha antagonists is a rare side effect of those drugs and has similarities with and differences from classical psoriasis in clinical and pathological characteristics.Treating severe paradoxical psoriasis is challenging because the reported cases are rare,with treatment experience being only anecdotal.CASE SUMMARY We report 2 cases of paradoxical psoriasis caused by infliximab.Both cases manifested with a significant number of pustular lesions and had protracted and complicated clinical courses.In case 1,secukinumab alone could not control the eruptions,but colchicine supplementation markedly decreased disease activity.In case 2 miscellaneous medications were administered,including the systemic drug acitretin,the immunosuppressive drug cyclosporine,and the biologic agent ustekinumab.However,multiple applications of those medications failed to prevent new lesions from occurring.Both cases showed moderate-to-high antinuclear antibody titers.CONCLUSION Based on these cases,moderate-to-high anti-nuclear antibody titer seems to be a risk factor for paradoxical psoriasis.In addition,extensive pustular presentation may be a negative prognostic indicator and may portend a protracted clinical course refractory to therapy.
基金Natural Science Foundation of Hebei Province(H2013206097)
文摘Generalized pustulous psoriasis is characterized by the sudden onset of diffuse erythema, with a scattering of pustules, sometimes with fever and others symptoms. It is a relatively rare disease^1. The treatment of traditional western medicine have various adverse drug reactions and easy to recur. Meanwhile, this report describes a 12-year-old female patient of generalized pustulous psoriasis with a satisfactory effect of traditional Chinese medicine.
基金The work was supported by grants from ShenZhen Medical Research Fund(No.C2401032)Sanming Project of Medicine in Shenzhen(No.SZSM202311022)Shenzhen Clinical Research Center for Rare Diseases(No.LCYSSQ20220823091402005).
文摘To the Editor:Annular pustular psoriasis(APP),a rare variant of generalized pustular psoriasis(GPP),manifests as recurrent,ring-shaped erythematous lesions adorned with small,sterile pustules,following a subacute trajectory.The recurrent nature of APP substantially diminishes patient quality of life.Owing to its infrequency,unified treatment protocols remain elusive.
基金supported by Beijing Natural Science Foundation(No.7242109)CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-059)+1 种基金the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-092)the Beijing Key Clinical Specialty Construction Project.
文摘Background:Generalized pustular psoriasis(GPP),a rare and recurrent autoinflammatory disease,imposes a substantial burden on patients and society.Awareness of GPP in China remains limited.Methods:This cross-sectional survey,conducted between September 2021 and May 2023 across 14 hospitals in China,included GPP patients of all ages and disease phases.Data collected encompassed demographics,clinical characteristics,economic impact,disease severity,quality of life,and treatment-related complications.Risk factors for GPP recurrence were analyzed.Results:Among 127 patients(female/male ratio=1.35:1),the mean age of disease onset was 25 years(1st quartile[Q1]–3rd quartile[Q3]:11–44 years);29.2%had experienced GPP for more than 10 years.Recurrence occurred in 75.6%of patients,and nearly half reported no identifiable triggers.Younger age at disease onset(P=0.021)and transitioning to plaque psoriasis(P=0.022)were associated with higher recurrence rates.The median diagnostic delay was 8 months(Q1–Q3:2–41 months),and 32.3%of patients reported misdiagnoses.Comorbidities were present in 53.5%of patients,whereas 51.1%experienced systemic complications during treatment.Depression and anxiety affected 84.5%and 95.6%of patients,respectively.During GPP flares,the median Dermatology Life Quality Index score was 19.0(Q1–Q3:13.0–23.5).This score showed significant differences between patients with and without systemic symptoms;it demonstrated correlations with both depression and anxiety scores.Treatment costs caused financial hardship in 55.9%of patients,underscoring the burden associated with GPP.Conclusions:The substantial disease and economic burdens among Chinese GPP patients warrant increased attention.Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
基金National Key R&D Program of China,Grant/Award Number:2023YFC2508101Beijing Hospitals Authority’s Ascent Plan,Grant/Award Number:DFI20241201
文摘Generalized pustular psoriasis(GPP)is a severe inflammatory cutaneous disease characterized by widespread pustules,edema,erythema,fever,and systemic inflammation.Chinese data indicate that the prevalence and incidence of GPP follow a bimodal age distribution,with peaks in the 0–3 year age group and the 30–39 year age group.1 In the 0–3 year age group,the prevalence was 0.927 and the incidence rate was 0.742 per 100000 population-years.1 Interleukin(IL)-36 plays an important role in GPP by activating nuclear factor-κB(NF-κB)and mitogen-activated protein kinase(MAPK)signal pathways.2 Chemokines(CXCL8,CXCL1,CXCL2,etc.),cytokines(IL-1β,tumor necrosis factor TNF-α,IL-6,IL-23,IL-17,etc.),and activated cells(e.g.,keratinocyte,neutrophils,dendritic cells,etc.)are also involved.3 Acitretin,cyclosporine,methotrexate,and etanercept were recommended as first-line treatments for children with GPP in 2012 by the American National Psoriasis Foundation.4 However,recent findings suggest that biological agents targeting IL-36,TNF-α,IL-17,IL-23,or their receptors might be more promising options than conventional drugs.5 Clinical trials and case series have also demonstrated the superiority of biological agents in adult and older pediatrics with GPP,including spesolimab,etanercept,adalimumab,secukinumab,brodalumab,and others.6 However,these biological agents,have only been approved by the FDA for children aged 4 years or older,and there is still limited data on their use in GPP patients under 4 years old.
基金This work was supported by the Babcock Endowment Fund(L.C.T.and J.E.G.),the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award numbers R01-AR060802(J.E.G.),P30-AR075043(J.E.G.),and K01-AR072129(L.C.T.),and the National Institute of Allergy and Infectious Diseases under award number R01-AR069071(J.E.G.),the A.Alfred Taubman Medical Research Institute(J.E.G.and J.M.K.),the National Psoriasis Foundation(J.E.G,N.L.W.,J.M.K.,E.M.,and L.C.T.),and the Parfait Emerging Scholar Award(J.M.K.).L.C.T.is supported by the Dermatology Foundation,the Arthritis National Research Foundation,and the National Psoriasis Foundation.
文摘Psoriasis is a chronic inflammatory skin condition that has a fairly wide range of clinical presentations.Plaque psoriasis,which is the most common manifestation of psoriasis,is located on one end of the spectrum,dominated by adaptive immune responses,whereas the rarer pustular psoriasis lies on the opposite end,dominated by innate and autoinflammatory immune responses.In recent years,genetic studies have identified six genetic variants that predispose to pustular psoriasis,and these have highlighted the role of IL-36 cytokines as central to pustular psoriasis pathogenesis.In this review,we discuss the presentation and clinical subtypes of pustular psoriasis,contribution of genetic predisposing variants,critical role of the IL-36 family of cytokines in disease pathophysiology,and treatment perspectives for pustular psoriasis.We further outline the application of appropriate mouse models for the study of pustular psoriasis and address the outstanding questions and issues related to our understanding of the mechanisms involved in pustular psoriasis.
基金grants from the National Natural Science Foundation of China，CAS "Light of West China" Program,Inner Mengolia Science and Technology Plan,the Youth Innovation Fund Project of Inner Mongolia Medical University，the Medical and Health Research Project of Inner Mongolia Health and Family Planning Commission，the Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region
文摘Background： Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis （GPP） is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 （TNIP1） gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Hart population. Methods： Seventy-three patients with GPP, 67 patients with palmoplantar pustulosis （PPP）, and 476 healthy controls were collected from Chinese Hart population. Six single nucleotide polymorphisms （SNPs） of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs 17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio （OR） （including 95% confidence interval） were calculated. The haplotype analysis was conducted by Haploview software. Results： The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group （P ≤ 7.22 × 10^-3）, especially in the GPP patients without psoriasis vulgaris （PsV）. In the haplotype analysis, the most significantly different haplotype was H4： ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group （OR = 4.16, P = 4.459 × 10^-7）. However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs （P 〉 0.05）. Conclusions： Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIPI might be a susceptibility gene for GPE
基金Natural Science Foundation of Beijing Municipality,Grant/Award Number:7212037The Pediatric Medical Coordinated Development Center of Beijing Municipal Administration,Grant/Award Number:XTZD20180502
文摘Generalized pustular psoriasis(GPP)is a severe subtype of psoriasis,commonly combined with systemic inflammation.Gene mutations have been found to be associated with GPP and vary by ethnicity.Systemic treatments are usually required for the severity and potential complications of GPP.However,there is no common consensus in China,especially among pediatric patients,whose data are scarce.Acitretin,methotrexate,and cyclosporine are widely used in pediatrics with GPP,while the adverse effects should be highlighted.The emergence of different biological agents brings us into a new era.This article discusses the genetic background of Chinese patients and demonstrates the evidence of treatment in pediatrics with GPP.
文摘Generalized pustular psoriasis(GPP)is a rare and life-threatening autoinflammatory skin disease characterized by recurrent and sudden episodes of widespread rashes with scattered sterile pustules.Clinical and genetic evidence indicates that the pathogenesis of GPP both overlaps and is separate from psoriasis vulgaris(PV).Interleukin(IL)-23/IL-17 immune pathway is well known to play a critical role in the immunopathogenesis of PV,while the inflammation of GPP is more inclined to involve the innate immune response via the IL-1/IL-36-chemokine pathway.Mutations in IL36RN,CARD13,AP1S3,MPO,TNIP1,SERPINA3,and SERPINA1 have been shown to be associated with GPP,among which loss-of-function mutation in IL36RN is the dominant mutation with the highest prevalence.Recent studies have shown that interaction of the IL-36 pathway and the IL-23/IL-17 axis underlies the immunological disturbances of GPP,indicating that innate and adaptive immune responses intertwine in the pathogenesis of GPP.With this deeper understanding of the pathogenesis of GPP,treatment by biologics targeting the IL-1/IL-36 pathway appears to be promising.IL-1 inhibitors,anakinra,canakinumab,and gevokizumab have reportedly been effective in some cases.Spesolimab and imsidolimab,which are antibodies to the IL-36 receptor,are undergoing investigation in a phase II trial and showing promising results.In the present review,we illustrate the current understanding of the pathogenesis of GPP based on recent updates on the molecular genetics and immunopathology of GPP and review recent clinical trials and case reports of novel biologics in the treatment of GPP.
基金supported by the Shaanxi Province Key R&D Program(No.S2019-YF-GXYB-0170).
文摘Objective:This study was performed to investigate the clinical characteristics of patients with generalized pustular psoriasis(GPP)in Northwest China.Methods:The clinical data of patients with GPP were retrospectively collected in the Second Affiliated Hospital of Xi’an Jiaotong University from January 1,2017,to December 31,2021 and analyzed using the chi-square test and Mann-Whitney U test.Results:In total,179 hospitalized patients were included.The male:female ratio was 1.16:1.00,and the mean age at onset was 35.05±19.11 years.Psoriasis vulgaris was also present in 76.0%of patients,and a family history of psoriasis was present in 15.6%.The mean duration of hospitalization was 10.67±4.31 days,and the mean duration of flares was 29.58±24.32 days.Infections and suspected drugs were predisposing factors.A fever developed in 54.7%of patients,and pruritus developed in 70.9%.Some patients had involvement of the nails(38.0%),scalp(46.9%),and tongue(4.5%).Cardiovascular disease,hypertension,and gallbladder-related disease were common comorbidities.The efficacy of acitretin was 84.7%,that of methotrexate was 66.7%,and that of cyclosporine was 100%.Fifteen patients were treated with secukinumab or adalimumab and responded well.The mean response time was 6.34±2.91 days based on the combination treatments.The mean duration of the treatment regimen was 111.35±94.25 days,and approximately 46.6%(n=131)of patients developed recurrence.Conclusion:Our retrospective study showed that most cases of GPP were accompanied by psoriasis vulgaris and associated with fever or pruritus.Acitretin had good therapeutic efficacy,but recurrence should be noted.Biologics are increasingly becoming effective treatments,but their superiority and safety need further research.
文摘Introduction:Generalized pustular psoriasis(GPP)is a rare life-threatening subtype of psoriasis and continues to be a therapeutic challenge.The first line therapies include acitretin,cyclosporin A,and methotrexate which have long-term side effects for children.Adalimumab has a favorable safety profile with low rates of adverse events,and has been described for successful treatment of adults with GPP in a few reports.We herein describe a 3-year-old girl with a body weight of 14.2 kg in whom adalimumab was used to successfully treat GPP.Case presentation:A 3-year-old girl with a 10-day history of systemic symptoms of fever,malaise,and the onset of studded painful pustules overlying an erythematous base on the scalp,face,neck,trunk,and bilateral extremities,affecting a body surface area of 90%.Laboratory examination results were notable for leukocytosis and elevated inflammatory markers.Biopsy confirmed the diagnosis of GPP.After failure of conventional therapies including cyclosporine and methotrexate,the patient began off-label treatment with adalimumab and achieved complete lesion clearance.During 14-month follow-up,she remains in remission on maintenance adalimumab therapy.Discussion:No consensus on the standard treatment regimen for GPP has been reached.Unfortunately,all drugs that have been reported to be effective for GPP are off-label.These treatments include systemic immunomodulators such as cyclosporine and methotrexate,systemic retinoids such as acitretin and isotretinoin,and various biologics.Our findings lend weight to the scant evidence describing the effective use of adalimumab in the treatment of pediatric GPP.Conclusion:Off-label use of adalimumab may be an effective and safe therapeutic option for GPP.
