泛发性脓疱型银屑病的诊疗：进展、挑战及展望

doi:10.35541/cjd.20250249

中华皮肤科杂志 ›› 2025, Vol. 58 ›› Issue (11): 1015-1019.doi: 10.35541/cjd.20250249

泛发性脓疱型银屑病的诊疗：进展、挑战及展望

邵帅王刚

空军军医大学西京医院皮肤科，西安 710032

收稿日期:2025-04-30 修回日期:2025-06-10 发布日期:2025-11-03
通讯作者: 王刚 E-mail:xjwgang@fmmu.edu.cn
基金资助:
国家自然科学基金（82322057）

Treatment and diagnosis of generalized pustular psoriasis: advances, challenges, and prospects

Shao Shuai, Wang Gang

Department of Dermatology, Xijing Hospital, Air Force Medical University, Xi′an 710032, China

Received:2025-04-30 Revised:2025-06-10 Published:2025-11-03
Contact: Wang Gang E-mail:xjwgang@fmmu.edu.cn
Supported by:
National Natural Science Foundation of China（82322057）

摘要/Abstract

摘要： 【摘要】泛发性脓疱型银屑病（GPP）是一种罕见、严重的自身炎症性疾病。近年遗传学、免疫学及靶向治疗的突破，使GPP的发病机制逐渐明晰，诊断标准和治疗策略不断优化，但仍存在许多未解决的问题，患者临床表型与治疗应答的差异、病情复发的预测与控制是当前面临的新挑战。未来GPP的研究重点将聚焦于深度解析其免疫机制和关键炎症信号通路，发现新的治疗靶点，并以此为基础探索疗效更优、更持久的临床治疗方案。

关键词: 银屑病, 泛发性脓疱型银屑病, 发病机制, 治疗, 治疗靶点, 中性粒细胞

Abstract: 【Abstract】 Generalized pustular psoriasis （GPP） is a rare and life-threatening autoinflammatory disorder. Recent advances in genetics, immunology, and targeted therapies have made its pathogenesis increasingly clear and led to refinements in diagnostic criteria and treatment strategies. Nonetheless, several challenges remain unresolved, including the heterogeneity of clinical phenotypes and therapeutic responses, as well as the prediction and control of disease relapse. Future research will focus on dissecting the immune mechanisms and pivotal inflammatory signaling pathways underlying GPP, identifying novel therapeutic targets, and developing more effective and durable treatment regimens based on research findings.

Key words: Psoriasis, Generalized pustular psoriasis, Pathogenesis, Therapy, Therapeutic targets, Neutrophils

邵帅王刚. 泛发性脓疱型银屑病的诊疗：进展、挑战及展望[J]. 中华皮肤科杂志, 2025,58(11):1015-1019. doi:10.35541/cjd.20250249

Shao Shuai, Wang Gang. Treatment and diagnosis of generalized pustular psoriasis: advances, challenges, and prospects[J]. Chinese Journal of Dermatology, 2025, 58(11): 1015-1019.doi:10.35541/cjd.20250249

参考文献 42

［1］	Feng JN, Guo JZ, Zhang Q, et al. Higher prevalence of generalized pustular psoriasis in Asia? A population⁃based study using claim data in China and a systematic review［J］. Dermatology, 2023,239（2）:195⁃205. doi: 10.1159/000528850.
［2］	Onoufriadis A, Simpson MA, Pink AE, et al. Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis［J］. Am J Hum Genet, 2011,89（3）:432⁃437. doi: 10. 1016/j.ajhg.2011.07.022.
［3］	Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin⁃36⁃receptor antagonist deficiency and generalized pustular psoriasis［J］. N Engl J Med, 2011,365（7）:620⁃628. doi: 10.1056/NEJ Moa1013068.
［4］	Elias M, Zhao S, Le HT, et al. IL⁃36 in chronic inflammation and fibrosis ⁃ bridging the gap?［J］. J Clin Invest, 2021,131（2）:e144336. doi: 10.1172/JCI144336.
［5］	Berki DM, Liu L, Choon SE, et al. Activating CARD14 mutations are associated with generalized pustular psoriasis but rarely account for familial recurrence in psoriasis vulgaris［J］. J Invest Dermatol, 2015,135（12）:2964⁃2970. doi: 10.1038/jid.2015.288.
［6］	Setta⁃Kaffetzi N, Simpson MA, Navarini AA, et al. AP1S3 mutations are associated with pustular psoriasis and impaired Toll⁃like receptor 3 trafficking［J］. Am J Hum Genet, 2014,94（5）:790⁃797. doi: 10.1016/j.ajhg.2014.04.005.
［7］	Haskamp S, Bruns H, Hahn M, et al. Myeloperoxidase modulates inflammation in generalized pustular psoriasis and additional rare pustular skin diseases［J］. Am J Hum Genet, 2020,107（3）:527⁃538. doi: 10.1016/j.ajhg.2020.07.001.
［8］	Frey S, Sticht H, Wilsmann⁃Theis D, et al. Rare loss⁃of⁃function mutation in SERPINA3 in generalized pustular psoriasis［J］. J Invest Dermatol, 2020,140（7）:1451⁃1455. doi: 10.1016/j.jid. 2019.11.024.
［9］	Kantaputra P, Chaowattanapanit S, Kiratikanon S, et al. SERPINA1, generalized pustular psoriasis, and adult⁃onset immunodeficiency［J］. J Dermatol, 2021,48（10）:1597⁃1601. doi: 10.1111/1346⁃8138.16081.
［10］	Zhang Q, Shi P, Wang Z, et al. Identification of the BTN3A3 gene as a molecule implicated in generalized pustular psoriasis in a Chinese population［J］. J Invest Dermatol, 2023,143（8）:1439⁃1448.e21. doi: 10.1016/j.jid.2023.01.023.
［11］	Yoshikawa T, Takeichi T, Nishida K, et al. MEFV variants are a predisposing factor for generalized pustular psoriasis［J］. J Am Acad Dermatol, 2024,90（4）:852⁃854. doi: 10.1016/j.jaad. 2023.10.070.
［12］	Han JW, Wang Y, Alateng C, et al. Tumor necrosis factor⁃alpha induced protein 3 interacting protein 1 gene polymorphisms and pustular psoriasis in Chinese Han population［J］. Chin Med J （Engl）, 2016,129（13）:1519⁃1524. doi: 10.4103/0366⁃6999. 184470.
［13］	Johnston A, Xing X, Wolterink L, et al. IL⁃1 and IL⁃36 are dominant cytokines in generalized pustular psoriasis［J］. J Allergy Clin Immunol, 2017,140（1）:109⁃120. doi: 10.1016/j.jaci.2016.08.056.
［14］	Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasis［J］. N Engl J Med, 2021,385（26）:2431⁃2440. doi: 10.1056/NEJMoa2111563.
［15］	Morita A, Strober B, Burden AD, et al. Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares （Effisayil 2）: an international, multicentre, randomised, placebo⁃controlled trial［J］. Lancet, 2023,402（10412）:1541⁃1551. doi: 10.1016/S0140⁃6736（23）01378⁃8.
［16］	Gordon KB, Augustin M, Barker J, et al. Effect of spesolimab on sustained disease control in patients with generalized pustular psoriasis: post hoc analysis of the EFFISAYIL 2 study［J］. J Am Acad Dermatol, 2025,92（6）:1235⁃1242. doi: 10.1016/j.jaad. 2025.01.089.
［17］	中国医师协会皮肤科医师分会儿童学组, 中华医学会皮肤性病学分会银屑病学组. 儿童脓疱型银屑病诊疗中国专家共识（2025版）［J］. 中华皮肤科杂志, 2025,58（4）:297⁃306. doi: 10.35541/cjd.20240714.
［18］	Carrier Y, Ma HL, Ramon HE, et al. Inter⁃regulation of Th17 cytokines and the IL⁃36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis［J］. J Invest Dermatol, 2011,131（12）:2428⁃2437. doi: 10.1038/jid.2011.234.
［19］	Ovesen SK, Schulze⁃Osthoff K, Iversen L, et al. IkBζ is a key regulator of tumour necrosis factor⁃a and interleukin⁃17A⁃mediated induction of interleukin⁃36g in human keratinocytes［J］. Acta Derm Venereol, 2021,101（2）:adv00386. doi: 10.2340/00015555⁃3749.
［20］	Friedrich M, Tillack C, Wollenberg A, et al. IL⁃36γ sustains a proinflammatory self⁃amplifying loop with IL⁃17C in anti⁃TNF⁃induced psoriasiform skin lesions of patients with Crohn's disease［J］. Inflamm Bowel Dis, 2014,20（11）:1891⁃1901. doi: 10.1097/MIB.0000000000000198.
［21］	Miyachi H, Konishi T, Kumazawa R, et al. Treatments and outcomes of generalized pustular psoriasis: a cohort of 1516 patients in a nationwide inpatient database in Japan［J］. J Am Acad Dermatol, 2022,86（6）:1266⁃1274. doi: 10.1016/j.jaad. 2021.06.008.
［22］	Torii H, Nakagawa H, Japanese Infliximab Study investigators. Long⁃term study of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma［J］. J Dermatol, 2011,38（4）:321⁃334. doi: 10.1111/j.1346⁃8138.2010. 00971.x.
［23］	Morita A, Nishikawa K, Yamada F, et al. Safety, efficacy, and drug survival of the infliximab biosimilar CT⁃P13 in post⁃marketing surveillance of Japanese patients with psoriasis［J］. J Dermatol, 2022,49（10）:957⁃969. doi: 10.1111/1346⁃8138.16508.
［24］	Morita A, Yamazaki F, Matsuyama T, et al. Adalimumab treatment in Japanese patients with generalized pustular psoriasis: results of an open⁃label phase 3 study［J］. J Dermatol, 2018,45（12）:1371⁃1380. doi: 10.1111/1346⁃8138.14664.
［25］	Imafuku S, Honma M, Okubo Y, et al. Efficacy and safety of secukinumab in patients with generalized pustular psoriasis: a 52⁃week analysis from phaseⅢ open⁃label multicenter Japanese study［J］. J Dermatol, 2016,43（9）:1011⁃1017. doi: 10.1111/1346⁃8138.13306.
［26］	Saeki H, Nakagawa H, Nakajo K, et al. Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: results from a 52⁃week, open⁃label, phase 3 study （UNCOVER⁃J）［J］. J Dermatol, 2017,44（4）:355⁃362. doi: 10.1111/1346⁃8138.13622.
［27］	Sano S, Kubo H, Morishima H, et al. Guselkumab, a human interleukin⁃23 monoclonal antibody in Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis: efficacy and safety analyses of a 52⁃week, phase 3, multicenter, open⁃label study［J］. J Dermatol, 2018,45（5）:529⁃539. doi: 10.1111/1346⁃8138.14294.
［28］	Imafuku S, Okubo Y, Tada Y, et al. Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in Japanese patients with moderate to severe plaque, erythrodermic, or generalized pustular psoriasis: efficacy and safety results from an open⁃label, phase 3 trial［J］. J Dermatol, 2024,51（3）:365⁃379. doi: 10.1111/1346⁃8138.17074.
［29］	Rhoads J, Lavasani L, Rasouliyan L, et al. Real⁃world clinical characteristics and treatment patterns of generalized pustular psoriasis flares［J］. J Am Acad Dermatol, 2025,92（6）:1243⁃1251. doi: 10.1016/j.jaad.2025.02.018.
［30］	Yu N, Qin H, Yu Y, et al. A distinct immature low⁃density neutrophil population characterizes acute generalized pustular psoriasis［J］. J Invest Dermatol, 2022,142（10）:2831⁃2835.e5. doi: 10.1016/j.jid.2022.04.011.
［31］	Haskamp S, Frey B, Becker I, et al. Transcriptomes of MPO⁃deficient patients with generalized pustular psoriasis reveals expansion of CD4+ cytotoxic T Cells and an involvement of the complement system［J］. J Invest Dermatol, 2022,142（8）:2149⁃2158.e10. doi: 10.1016/j.jid.2021.12.021.
［32］	Baldo A, Domizio JD, Yatim A, et al. Human neutrophils drive skin autoinflammation by releasing interleukin （IL）⁃26［J］. J Exp Med, 2024,221（5）:e20231464. doi: 10.1084/jem.20231464.
［33］	Viguier M, Bentayeb M, Azzi J, et al. Generalized pustular psoriasis: a nationwide population⁃based study using the national health data system in France［J］. J Eur Acad Dermatol Venereol, 2024,38（6）:1131⁃1139. doi: 10.1111/jdv.19901.
［34］	Lee CC, Huang YH, Chi CC, et al. Generalized pustular psoriasis: immunological mechanisms, genetics, and emerging therapeutics［J］. Trends Immunol, 2025,46（1）:74⁃89. doi: 10. 1016/j.it.2024.12.001.
［35］	Choon SE, Lebwohl MG, Turki H, et al. Clinical characteristics and outcomes of generalized pustular psoriasis flares［J］. Dermatology, 2023,239（3）:345⁃354. doi: 10.1159/000529274.
［36］	Xu Z, Liu Y, Zhang J, et al. Development and validation of a prognostic model for predicting flares in generalized pustular psoriasis［J］. J Eur Acad Dermatol Venereol, 2024,38（7）:e599⁃e601. doi: 10.1111/jdv.19764.
［37］	Navarini AA, Burden AD, Capon F, et al. European consensus statement on phenotypes of pustular psoriasis［J］. J Eur Acad Dermatol Venereol, 2017,31（11）:1792⁃1799. doi: 10.1111/jdv. 14386.
［38］	Fujita H, Terui T, Hayama K, et al. Japanese guidelines for the management and treatment of generalized pustular psoriasis: the new pathogenesis and treatment of GPP［J］. J Dermatol, 2018,45（11）:1235⁃1270. doi: 10.1111/1346⁃8138.14523.
［39］	Choon SE, van de Kerkhof P, Gudjonsson JE, et al. International consensus definition and diagnostic criteria for generalized pustular psoriasis from the international psoriasis council［J］. JAMA Dermatol, 2024,160（7）:758⁃768. doi: 10.1001/jamadermatol. 2024.0915.
［40］	《脓疱型银屑病诊疗中国专家共识（2022版）》编写委员会专家组. 脓疱型银屑病诊疗中国专家共识（2022版）［J］. 中华皮肤科杂志, 2022,55（3）:187⁃195. doi: 10.35541/cjd.20210698.
［41］	Choon SE, Tok P, Wong KW, et al. Clinical profile of patients with acute generalized pustular psoriasis with and without IL36RN mutations in multi⁃ethnic Johor Bahru, Malaysia［J］. Exp Dermatol, 2023,32（8）:1263⁃1271. doi: 10.1111/exd.14776.
［42］	Farag A, Visvanathan S, Bachelez H, et al. Spesolimab reduces inflammation in generalized pustular psoriasis: molecular characterization of flare treatment in EFFISAYIL 1［J］. J Invest Dermatol, 2025,145（3）:573⁃582.e8. doi: 10.1016/j.jid.2024. 05.034.

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泛发性脓疱型银屑病的诊疗：进展、挑战及展望

Treatment and diagnosis of generalized pustular psoriasis: advances, challenges, and prospects

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