Recalcitrant paradoxical pustular psoriasis induced by infliximab:Two case reports

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.

Childhood pustular psoriasis--A case of a patient treated with traditional Chinese medicine

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.

“Autoinflammatory psoriasis”-genetics and biology of pustular psoriasis

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.

Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein I Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population

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

The update of treatment strategies in pediatrics with generalized pustular psoriasis in China

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.

Understanding the Pathogenesis of Generalized Pustular Psoriasis Based on Molecular Genetics and Immunopathology

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.

Characterization of Generalized Pustular Psoriasis in Northwest China: A Single-Center Retrospective Study

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.