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Okubo Y, Okuyama R, Imafuku S, Tada Y, Yamanaka K, Sugiura K, Yamaguchi Y, Yasuda M, Sakamoto W, Saitoh M, Morita A, Study Investigators. Treatment Status for Generalized Pustular Psoriasis in Japanese Patients: A Retrospective Chart Review. Dermatol Ther (Heidelb) 2025; 15:1883-1899. [PMID: 40388057 DOI: 10.1007/s13555-025-01429-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Collaborators] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Accepted: 04/15/2025] [Indexed: 06/01/2025] Open
Abstract
INTRODUCTION Generalized pustular psoriasis (GPP) is a rare, severe, and chronic inflammatory skin disease characterized by widespread pustules that leads to unpredictable and potentially serious disease flares. Information regarding treatment status for GPP and treatment patterns for flares is important but limited as a result of the rarity of the condition. We conducted a 10-year, retrospective, longitudinal chart review of treatment patterns at GPP referral hospitals in Japan. METHODS Eligible patients with GPP had at least 6 months of continuous observation data within 10 years after the date of protocol approval. Data were collected from patient records and annual patient reports. Patient characteristics and treatment details, including in relation to flare occurrence, were analyzed. RESULTS The median age of patients (N = 205) was 53 years; 48.3% were female and most had mild or moderate GPP (66.8%). Patients commonly received nonbiologic systemic therapy (86.3%) and a similar proportion received biologics (79.5%); 95.1% received topical treatment and 22.4% received systemic adrenal corticosteroids. Use of nonbiologic systemic therapy decreased, and use of biologics increased, over the study period. During the observation period, the proportion of patients receiving biologic therapy increased after a flare (from 41.4% receiving biologics when flares occurred to 62.9% initiating a new biologic post flare). CONCLUSION In Japanese clinical practice, the evolution of treatment practices for GPP has seen an increased use of biologic therapies over time. Biologic use was common after flares; however, some flares occurred during biologic therapy, indicating a need for improved treatment options to maintain stable disease and prevent flares.
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Affiliation(s)
- Yukari Okubo
- Department of Dermatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
| | - Ryuhei Okuyama
- Department of Dermatology, School of Medicine, Shinshu University, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Shinichi Imafuku
- Faculty of Medicine-Dermatology, Fukuoka University, 7-45-1 Nanakuma, Fukuoka, 814-0180, Japan
| | - Yayoi Tada
- Department of Dermatology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan
| | - Keiichi Yamanaka
- Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Kazumitsu Sugiura
- Department of Dermatology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan
| | - Yukie Yamaguchi
- Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Masahito Yasuda
- Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Wataru Sakamoto
- Nippon Boehringer Ingelheim, Think Power Tower 2-1-1, Osaki Shinagawa-ku, Tokyo, 141-6017, Japan
| | - Morihisa Saitoh
- Nippon Boehringer Ingelheim, Think Power Tower 2-1-1, Osaki Shinagawa-ku, Tokyo, 141-6017, Japan
| | - Akimichi Morita
- Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
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Collaborators
Akimichi Morita, Ryuhei Okuyama, Kenji Kabashima, Yukie Yamaguchi, Koji Masuda, Yoko Muzutani, Keiichi Yamanaka, Takuro Kanekura, Shigeto Yanagihara, Chiharu Tateishi, Yukari Okubo, Yayoi Tada, Tetsuya Honda, Satoshi Fukushima, Kazuki Yatsuzuka, Takuya Miyagi, Masahito Yasuda, Emi Yokoyama, Mayumi Komine, Nobuo Kanazawa, Kazumitsu Sugiura, Masahiro Amano, Daisuke Watabe, Koremasa Hayama, Hitoshi Tsuchihashi, Masaru Honma, Masatoshi Abe, Hajime Iizuka, Akihiko Asahina,
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Rhoads JLW, Lavasani L, Rasouliyan L, Laouri M, Noe M. Real-world clinical characteristics and treatment patterns of generalized pustular psoriasis flares. J Am Acad Dermatol 2025; 92:1243-1251. [PMID: 39933611 DOI: 10.1016/j.jaad.2025.02.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 02/04/2025] [Accepted: 02/06/2025] [Indexed: 02/13/2025]
Abstract
BACKGROUND Clinical characteristics and treatment of generalized pustular psoriasis (GPP) flares are poorly understood. OBJECTIVE To characterize patients by GPP flare status, quantify flare timing/frequency, and understand peri-flare treatment patterns. METHODS This cohort study utilized electronic health records (2017-2023) from outpatient dermatology clinics in the OMNY Health real-world data platform. Patients were indexed at first GPP diagnosis code; encounter-level GPP flare status was established from previously developed algorithms. Annualized flare rate, time between flares, and peri-flare treatment patterns were described. RESULTS Four hundred four of 638 patients (63%) experienced ≥1 flare episode. Patients who experienced a flare were more likely to be female, younger, nonwhite, Hispanic/Latino, have infectious/parasitic disease history, and more active GPP. Mean (median) annualized flare rate was 0.91 (0.51) flares/patient/year; mean (median) time between flares was 5.9 (3.8) months. Prescriptions increased from preflare period to flare episode, then decreased during the postflare period. Frequent treatment alterations of off-label biologics and nonsteroidal systemic agents were observed. LIMITATIONS Data were from US-based outpatient dermatology practices; documentation of GPP flares may not have been comprehensive or consistent in this setting. CONCLUSION GPP patients continue to experience frequent flares with traditional off-label therapies. Patients' course of treatment was altered frequently, suggesting an unmet need for effective long-term GPP therapies.
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Affiliation(s)
- Jamie L W Rhoads
- Department of Dermatology, University of Utah School of Medicine, Salt Lake City, Utah
| | - Layla Lavasani
- Health Economics and Outcomes Research, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut.
| | | | - Marianne Laouri
- Health Economics and Outcomes Research, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut
| | - Megan Noe
- Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts
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Aithal VV, Bhat R, Das S, Dogra S, Godse K, Shankar DSK, Nayak CS, Pai SB, Parasramani SG, Parthasaradhi A, Shah B, Tahiliani ST, Toms T, Dahiya AK. Indian expert Delphi consensus on the diagnosis and management of flares of generalised pustular psoriasis. Indian J Dermatol Venereol Leprol 2025; 91:338-345. [PMID: 39361853 DOI: 10.25259/ijdvl_219_2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 06/30/2024] [Indexed: 10/05/2024]
Abstract
Generalised pustular psoriasis (GPP) is a chronic, multisystemic, autoinflammatory disease with predominantly cutaneous manifestations, characterised by recurrent episodes of widespread, macroscopic and aseptic pustules. It has a highly unpredictable, heterogeneous and unstable clinical course. There are no consensus guidelines in India for the management of GPP. The objective of this Delphi panel study was to achieve consensus on problem areas in the understanding and management of GPP. Based on the inputs from an expert panel, 19 topics across six domains were identified as being important regarding the understanding and management of GPP. Statements were developed for these 19 topics, and consensus for the statements was sought using the modified Delphi method. Twelve experts evaluated the statements, indicating their agreement or disagreement. Consensus was considered to be reached when ≥80% of experts agreed with a statement. After two rounds of discussion, consensus was reached for 17 out of 19 (89%) statements and no consensus was achieved for two (11%) statements. We have presented the statements along with the respective degrees of consensus. Wherever relevant, clarifications or additional comments by experts are provided in the document.
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Affiliation(s)
| | - Ramesh Bhat
- Department of Dermatology, Venereology & Leprosy, Fr. Muller Medical College Kankanady, Mangalore, India
| | - Sudip Das
- Department of Dermatology, Calcutta National Medical College, Beniapukur, Kolkata, India
| | - Sunil Dogra
- Department of Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Kiran Godse
- Department of Dermatology, DY Patil Hospital, Nerul, Navi Mumbai, India
| | | | | | - Sathish B Pai
- Department of Dermatology, Kasturba Medical College, Manipal, MAHE, Manipal, India
| | | | | | - Bela Shah
- Department of Dermatology, STD & Leprosy, B. J. Medical College & Civil Hospital, Haripura, Asarwa, Ahmedabad, India
| | - Sushil T Tahiliani
- Department of Dermatology, PD Hinduja Hospital and Medical Research Centre, Mahim West, India
| | - Tomson Toms
- Department of Medical Affairs, Boehringer Ingelheim Pvt. Ltd., Godrej Two, Mumbai, Maharashtra, India
| | - Arun Kumar Dahiya
- Department of Medical Affairs, Boehringer Ingelheim Pvt. Ltd., Godrej Two, Mumbai, Maharashtra, India
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Schultze M, Kossack N, Kromer C, Zimmermann TM, Kolb N. Epidemiology of generalized pustular psoriasis in Germany: Analyzing factors influencing prevalence estimates health insurance data. J Dtsch Dermatol Ges 2025; 23:589-597. [PMID: 40026063 PMCID: PMC12087748 DOI: 10.1111/ddg.15633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 11/07/2024] [Indexed: 03/04/2025]
Abstract
BACKGROUND AND OBJECTIVES Generalized pustular psoriasis (GPP) is a rare, chronic, potentially life-threatening skin disease. We aimed to establish criteria to accurately approximate GPP prevalence in Germany. METHODS A retrospective analysis of the WIG2 health claims database (1/1/2016-31/12/2020) was conducted. Patients aged ≥ 12 years continuously enrolled in their statutory health insurance with one inpatient or confirmed outpatient diagnosis code for GPP (International Classification of Diseases, 10th Revision [ICD-10] L40.1) were included. Scenarios with increasingly strict criteria were used to identify the GPP population. RESULTS From 2016-2020, 5,236 potential GPP cases were identified based on a recorded GPP diagnosis. The scenario of ≥ 1 GPP diagnosis yielded the highest prevalence (336-390 patients/million) followed by > 1 GPP diagnosis in ≥ 2 quarters (189-288 patients/million); scenarios resulting in the lowest prevalence were diagnosis in ≥ 2 quarters AND two independent diagnoses (17-28/million) and diagnosis in ≥ 2 quarters AND two independent diagnoses or diagnosis by a specialist AND potential flare (58-61 patients/million). CONCLUSIONS This study suggests that diagnosis in ≥ 2 quarters by a specialist or two independent physicians may be the most clinically robust and reliable criteria for estimating GPP prevalence; therefore, 50-100 patients/million may represent a reasonable prevalence estimate range for Germany.
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Affiliation(s)
- Michael Schultze
- ZEG – Berlin Center for Epidemiology and Health ResearchBerlinGermany
| | - Nils Kossack
- WIG2 – Scientific Institute for Health Economics and Health System ResearchLeipzigGermany
| | - Christian Kromer
- Department of DermatologyVenereology, and Allergology, University Medical Center, GöttingenGöttingenGermany
| | | | - Nikolaus Kolb
- ZEG – Berlin Center for Epidemiology and Health ResearchBerlinGermany
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Wang H, Xu J, Yu X, Hao S, Chen X, Peng B, Li X, Wang P, Miao C, Guo J, Hu Q, Su Z, Wang S, Yu C, Sun Q, Zhang M, Yang B, Li Y, Song Z, Geng S, Chen A, Xu Z, Zhang C, Lu Q, Lu Y, Jiang X, Wang G, Fang H, Sun Q, Liu J, Jin H. Current status of generalized pustular psoriasis: Findings from a multicenter hospital-based survey of 127 Chinese patients. Chin Med J (Engl) 2025; 138:953-961. [PMID: 40097356 PMCID: PMC12037088 DOI: 10.1097/cm9.0000000000003494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Indexed: 03/19/2025] Open
Abstract
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.
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Affiliation(s)
- Haimeng Wang
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing 100730, China
| | - Jiaming Xu
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing 100730, China
| | - Xiaoling Yu
- Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong 510091, China
| | - Siyu Hao
- Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Xueqin Chen
- Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing 400038, China
| | - Bin Peng
- Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Xiaona Li
- Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Ping Wang
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Chaoyang Miao
- Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100044, China
| | - Jinzhu Guo
- Department of Dermatology, Peking University Third Hospital, Beijing 100191, China
| | - Qingjie Hu
- Hospital of Dermatology, Chinese Academy of Medical Sciences, Nanjing, Jiangsu 210042, China
| | - Zhonglan Su
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Sheng Wang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Chen Yu
- Department of Dermatology, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, China
| | - Qingmiao Sun
- Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China
| | - Minkuo Zhang
- Department of Dermatology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
| | - Bin Yang
- Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong 510091, China
| | - Yuzhen Li
- Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Zhiqiang Song
- Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing 400038, China
| | - Songmei Geng
- Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Aijun Chen
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Zigang Xu
- Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100044, China
| | - Chunlei Zhang
- Department of Dermatology, Peking University Third Hospital, Beijing 100191, China
| | - Qianjin Lu
- Hospital of Dermatology, Chinese Academy of Medical Sciences, Nanjing, Jiangsu 210042, China
| | - Yan Lu
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Xian Jiang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Gang Wang
- Department of Dermatology, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, China
| | - Hong Fang
- Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China
| | - Qing Sun
- Department of Dermatology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
| | - Jie Liu
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing 100730, China
| | - Hongzhong Jin
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing 100730, China
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Imafuku S, Satoh A, Arima H, Tsuruta N, Iwasaki R, Kimura H. Quality of life of patients with pustular psoriasis is inferior to that of patients with plaque psoriasis in Japan: A multicenter study with questionnaires, the short Form-36, and other patient-reported outcomes. J Dermatol 2025; 52:682-694. [PMID: 40001311 DOI: 10.1111/1346-8138.17629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 12/23/2024] [Accepted: 01/05/2025] [Indexed: 02/27/2025]
Abstract
Generalized pustular psoriasis is a rare but severe form of psoriasis, accounting for 7.5% of all psoriasis cases. We investigated whether the disease burden and quality of life of patients with generalized pustular psoriasis were lower than those of patients with psoriasis vulgaris in Japan. Patients registered in the Western Japan Psoriasis Registry, a prospective cohort of patients with psoriasis treated at 31 facilities specializing in psoriasis medicine, were surveyed using the SF-36v2 and other patient-reported outcomes. We enrolled patients with generalized pustular psoriasis (n = 97) and psoriasis vulgaris (n = 1065). The generalized pustular psoriasis group had fewer males, were younger at onset, had fewer smokers and habitual drinkers, and were more frequently treated with biologics than patients with psoriasis vulgaris. Questions on disease burden revealed that patients with generalized pustular psoriasis experienced sores, blisters, skin pain, and systemic symptoms more frequently than patients with psoriasis vulgaris. A higher proportion of patients with generalized pustular psoriasis had joint pain and fatigue than those with psoriasis vulgaris, although patient satisfaction with treatment did not differ significantly between the two groups. The Short Form-36 evaluation revealed that patients with generalized pustular psoriasis had significantly lower physical component summary scores than patients with psoriasis vulgaris. These findings indicate that patients with generalized pustular psoriasis have a higher burden and more impaired quality of life than patients with psoriasis vulgaris.
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Affiliation(s)
- Shinichi Imafuku
- Department of Dermatology, School of Medicine, Fukuoka University, Fukuoka, Japan
| | - Atsushi Satoh
- Department of Preventive Medicine & Public Health, School of Medicine, Fukuoka University, Fukuoka, Japan
| | - Hisatomi Arima
- Department of Preventive Medicine & Public Health, School of Medicine, Fukuoka University, Fukuoka, Japan
| | - Noriko Tsuruta
- Division of Dermatology, Kitakyushu Yahata Hospital, Fukuoka, Japan
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Tada Y, Imafuku S, Sugiura K, Fujita H, Tsuruta N, Mitsuma T, Yoshizaki A, Abe M, Yamaguchi Y, Morita A. Treating Generalized Pustular Psoriasis (GPP): Timing and Rationale for Biologic Treatment Switching-A Japanese e-Delphi Survey. Dermatol Ther (Heidelb) 2025; 15:1009-1024. [PMID: 40121384 PMCID: PMC11971113 DOI: 10.1007/s13555-025-01377-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 02/26/2025] [Indexed: 03/25/2025] Open
Abstract
INTRODUCTION Generalized pustular psoriasis (GPP) is a chronic, inflammatory disease characterized by the sudden and recurrent development of widespread sterile pustules on the skin. The treatment of GPP includes non-biologic and biologic therapies. In Japan, biologic agents are being increasingly used as first-line treatment, with more biologics approved in Japan than in other countries. A previous secondary data-based study utilizing data in the Medical Data Vision database and the Japan Medical Data Center in Japan demonstrated heterogeneity in real-world biologic treatment patterns, with at least one switch during the follow-up period (mean n switches 3.8; mean length of follow-up 3.3 years) for approximately one third of patients with GPP treated with a biologic drug. The aim of this study was to evaluate where consensus lies among experts regarding switching biologic treatments for patients with GPP in Japan. METHODS A Delphi exercise that consists of three survey rounds was performed with ten Japanese dermatologists. Participants were asked to respond to questions related to experts' experience with specific biologics, experience with switching, timing of switches and importance of specific criteria (drivers) when making the decision to switch. The consensus threshold was 70%. RESULTS Based on the results of the Delphi exercise, most experts rarely (60%) or never (20%) switch a biologic agent and only 20% switch often during acute symptoms/GPP flare driven by the short time of the flare; this result may be different during the maintenance phase. Lack of efficacy, loss of efficacy due to long-term use, side effects, contraindications, new products with better efficacy and safety evidence, risk of infection, and lack of adherence play an important role in making the decision to switch. CONCLUSION Switches may occur for patients on biologics when flares occur (loss of effectiveness) or when there is insufficient response (lack of effectiveness). The decision to switch a biologic is impacted by several other criteria, including safety and the availability of more efficacious and better tolerated therapies. Overall, there is still an unmet need for robust evidence to inform GPP treatment choice.
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Affiliation(s)
- Yayoi Tada
- Department of Dermatology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-Ku, Tokyo, Japan.
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Marzano AV, Fargnoli MC, Gisondi P, Balato A, Bianchi L, Calzavara-Pinton P, Chiricozzi A, Costanzo A, Megna M, Micali G, Piaserico S, Prignano F. Literature review and expert opinion on diagnosis and current management of generalized pustular psoriasis. Expert Opin Biol Ther 2025; 25:265-273. [PMID: 39925164 DOI: 10.1080/14712598.2025.2464858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 12/17/2024] [Accepted: 02/05/2025] [Indexed: 02/11/2025]
Abstract
INTRODUCTION Generalized pustular psoriasis (GPP) is a rare, chronic, systemic, autoinflammatory disease characterized by the eruption of sterile pustules, often accompanied by more general symptoms, such as fever, fatigue, and a burning sensation in the skin. GPP can be potentially life-threatening, if untreated, as it can lead to complications, such as sepsis and heart failure. AREAS COVERED In this literature review and expert opinion article, we provide an overview of the epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of GPP. Eleven dermatologists representing seven different Italian regions considered relevant evidence in the literature to discuss the current diagnosis and treatment of GPP. The expert panel of dermatologists identified several weaknesses in the current clinical management of GPP. EXPERT OPINION There is an inconsistent definition and classification of the disease across the literature, which can lead to misdiagnosis and delay in disease treatment. Furthermore, there are no international and standardized clinical guidelines on disease management, especially in Europe. There is a profound need for the development of novel therapeutic agents with sustained efficacy to decrease the impact of the comorbidities and mortality associated with GPP, prevent the onset of complications, and support the unmet needs of these patients.
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Affiliation(s)
- Angelo Valerio Marzano
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Maria Concetta Fargnoli
- Dermatology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Paolo Gisondi
- Department of Medicine, Section of Dermatology and Venereology, University of Verona, Verona, Italy
| | - Anna Balato
- Dermatology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Luca Bianchi
- UOSD of Dermatology, Policlinico Tor Vergata, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | | | - Andrea Chiricozzi
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- U.O.C. Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Costanzo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Dermatology unit, Humanitas Clinical and Research Center, IRCCS Scientific Institute for Research, Hospitalization and Healthcare, Rozzano, Italy
| | - Matteo Megna
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | | | - Stefano Piaserico
- Dermatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | - Francesca Prignano
- Department of Health Science, Section of Dermatology, University of Firenze, Firenze, Italy
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Farag A, Visvanathan S, Bachelez H, Morita A, Lebwohl MG, Barker JN, Choon SE, Burden AD, Tsai TF, Leparc G, Delic D, Lang B, Thoma C, Krueger JG. Spesolimab Reduces Inflammation in Generalized Pustular Psoriasis: Molecular Characterization of Flare Treatment in EFFISAYIL 1. J Invest Dermatol 2025; 145:573-582.e8. [PMID: 39004117 DOI: 10.1016/j.jid.2024.05.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 05/22/2024] [Accepted: 05/30/2024] [Indexed: 07/16/2024]
Abstract
EFFISAYIL 1 was a randomized, placebo-controlled study of spesolimab, an anti-IL-36 receptor antibody, in patients presenting with a generalized pustular psoriasis flare. Treatment with spesolimab led to more rapid pustular and skin clearance versus treatment with placebo in approximately half of the patients. In this study, we present histologic, transcriptomic, and proteomic analyses of lesional and nonlesional skin and whole-blood samples collected from EFFISAYIL 1. Treatment with spesolimab led to a transition toward a nonlesional profile, with a downregulation of gene expressions in the skin of IL-36 transcripts (IL36α, IL36β, IL36γ) and those associated with neutrophil recruitment (CXCL1, CXCL6, CXCL8), proinflammatory cytokines (IL6, IL19, IL20), and skin inflammation (DEFB4A, S100A7, S100A8). Changes were manifest at week 1 and sustained to week 8. At the systemic level, reductions in serum biomarkers of inflammation (IL-17, IL-8, IL-6) were sustained until 12 weeks after spesolimab treatment. Considerable overlap was observed in the spesolimab-induced changes in gene and protein expressions from skin and blood samples, demonstrating the molecular basis of the effects of spesolimab on controlling local and systemic inflammation. Data are consistent with the mode of action of spesolimab, whereby inhibition of the IL-36 pathway leads to subsequent reductions in the key local and systemic pathologic events associated with generalized pustular psoriasis flares.
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Affiliation(s)
- Ahmed Farag
- Boehringer Ingelheim Pharma, Biberach, Germany
| | | | - Hervé Bachelez
- Service de Dermatologie, Assistance Publique-Hôpitaux de Paris Hôpital Saint-Louis, Paris, France; INSERM Unité 1163, Imagine Institute of Genetic Diseases, Université Paris Cité, Paris, France
| | - Akimichi Morita
- Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Mark G Lebwohl
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jonathan N Barker
- St John's Institute of Dermatology, King's College London, London, United Kingdom
| | - Siew Eng Choon
- Jeffrey Cheah School of Medicine and Health Sciences, Clinical School Johor Bahru, Monash University Malaysia, Johor Bahru, Malaysia
| | - A David Burden
- School of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom
| | - Tsen-Fang Tsai
- Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | | | - Denis Delic
- Boehringer Ingelheim Pharma, Biberach, Germany
| | | | | | - James G Krueger
- Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA
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10
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Elewski B, Lebwohl MG. Management of Chronic Generalized Pustular Psoriasis: A Review and Expert Opinion. JOURNAL OF PSORIASIS AND PSORIATIC ARTHRITIS 2025:24755303251318976. [PMID: 39906749 PMCID: PMC11789050 DOI: 10.1177/24755303251318976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 01/09/2025] [Accepted: 01/19/2025] [Indexed: 02/06/2025]
Abstract
Introduction: Generalized pustular psoriasis (GPP) is a rare, chronic inflammatory skin disease characterized by persistent symptoms and sudden flares of painful sterile pustules, sometimes accompanied by systemic inflammation. Patients with GPP experience chronic disease burden even when not experiencing flares. There is an unmet need for guidelines on continuous long-term management of this disease. Areas Covered: This review summarizes existing literature describing the chronic disease burden of GPP, the persistence of symptoms and effects on quality of life (QoL) when patients are not experiencing a flare, the recurring nature of GPP flares, and the high prevalence of chronic comorbidities. We also present an overview of results from the EFFISAYIL® 2 study, which was the first randomized, placebo-controlled clinical trial to systematically evaluate continuous management with subcutaneous spesolimab, a first-in-class anti-interleukin-36 receptor monoclonal antibody specifically designed to treat GPP. Expert Opinion: An unmet need in GPP is the establishment of guidelines for chronic disease management, including measures for treating GPP between flares, flare prevention, and long-term disease control. Treatment strategies should mitigate both the persistent disease burden and potentially life-threatening flare episodes. Intravenous spesolimab is currently the only FDA-approved medication to treat GPP flares, and subcutaneous spesolimab is the only FDA-approved medication to treat GPP when patients are not experiencing a flare. Guidelines should aim to advance the recognition of GPP as a chronic disease and emphasize prompt diagnosis and timely access to FDA-approved therapies according to the diagnostic criteria established by the International Psoriasis Council and the National Psoriasis Foundation.
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Affiliation(s)
- Boni Elewski
- Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Mark G. Lebwohl
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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11
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Pathak GN, Wang E, Dhillon J, Parikh PN, Esseghir R, Rao BK, Feldman SR. Spesolimab: A Review of the First IL-36 Blocker Approved for Generalized Pustular Psoriasis. Ann Pharmacother 2025; 59:174-183. [PMID: 38755971 DOI: 10.1177/10600280241252688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2024] Open
Abstract
OBJECTIVE This article reviews clinical trial data that assesses the safety, efficacy, and clinical application of spesolimab, an interleukin-36 (IL-36) blocker, for the treatment of generalized pustular psoriasis (GPP). DATA SOURCES A review of the literature was conducted using the search terms: "spesolimab," "BI 655130," and "spevigo" in MEDLINE (PubMed) and Clinicaltrials.gov from January 1, 1950 to October 31, 2023. STUDY SELECTION AND DATA EXTRACTION Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of spesolimab were included. DATA SYNTHESIS In one phase 2 clinical trial evaluating single dose IV spesolimab for GPP flares at day 8, 54% of patients receiving spesolimab had a GPP physician global assessment (GPPGA) pustulation subscore of 0, and 43% had a GPPGA total score of 0 compared with 6% and 11% for the placebo group, respectively. Another phase 2 clinical trial assessing subcutaneous spesolimab found 23% of patients in low-dose, 29% in medium-dose, and 10% of high-dose spesolimab had flares by week 48 compared with 52% of the placebo group. Hazard ratios for time to GPP flare compared with placebo were 0.16 (P = 0.0005), 0.35 (P = 0.0057), and 0.47 (P = 0.027) for the spesolimab groups, respectively. Infection rates were similar across treatment and placebo groups, and severe adverse events such as drug reactions with eosinophilia and systemic symptom (DRESS), cholelithiasis, and breast cancer occurred with spesolimab. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS Spesolimab is a first-in-class IL-36 monoclonal antibody receptor antagonist approved for the treatment of acute GPP flares. It is a safe and effective therapeutic agent in preventing future GPP flares, with no current comparator trials with other GPP agents. CONCLUSION Spesolimab is a safe and effective treatment for acute GPP flares in adults. Future clinical trials can establish safety and efficacy compared with other agents.
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Affiliation(s)
- Gaurav N Pathak
- Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Somerset, NJ, USA
- Center for Dermatology Research, Department of Dermatology, School of Medicine, Wake Forest University, Winston-Salem, NC, USA
| | - Emily Wang
- Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Somerset, NJ, USA
| | - Jimmy Dhillon
- Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Somerset, NJ, USA
| | - Prachi N Parikh
- Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Somerset, NJ, USA
| | - Reem Esseghir
- Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Somerset, NJ, USA
| | - Babar K Rao
- Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Somerset, NJ, USA
- Department of Dermatology, Rao Dermatology, Atlantic Highlands, NJ, USA
| | - Steven R Feldman
- Center for Dermatology Research, Department of Dermatology, School of Medicine, Wake Forest University, Winston-Salem, NC, USA
- Department of Pathology, School of Medicine, Wake Forest University, Winston-Salem, NC, USA
- Department of Social Sciences and Health Policy, School of Medicine, Wake Forest University, Winston-Salem, NC, USA
- Department of Dermatology, University of Southern Denmark, Odense, Denmark
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12
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Choon SE, Foley PA, Asawanonda P, Fujita H, Jo S, Shi Y, Theng C, Affandi AM, Bang CH, Frez ML, Huei HY, Le Huu D, Kim T, Morita A, Oon HH, Fernández‐Peñas P, Rajatanavin N, Robinson S, Selvarajah L, Tsai T. Asia-Pacific consensus recommendations on the management of generalized pustular psoriasis. J Dermatol 2024; 51:1579-1595. [PMID: 39390737 PMCID: PMC11624156 DOI: 10.1111/1346-8138.17471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 08/20/2024] [Accepted: 09/07/2024] [Indexed: 10/12/2024]
Abstract
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.
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Affiliation(s)
- Siew Eng Choon
- Clinical School Johor Bahru, Jeffrey Cheah School of Medicine & Health SciencesMonash UniversityJohor BahruMalaysia
| | - Peter Anthony Foley
- The University of Melbourne, St Vincent's Hospital MelbourneFitrozyVictoriaAustralia
- Skin Health InstituteCarltonVictoriaAustralia
| | | | - Hideki Fujita
- Division of Cutaneous Science, Department of DermatologyNihon University School of MedicineTokyoJapan
| | - Seong‐Jin Jo
- Department of DermatologySeoul National University College of MedicineSeoulRepublic of Korea
| | - Yu‐ling Shi
- Department of DermatologyShanghai Skin Disease Hospital, School of Medicine, Tongji UniversityShanghaiChina
- Institute of Psoriasis, School of Medicine, Tongji UniversityShanghaiChina
| | - Colin Theng
- The Skin Specialists & Laser ClinicSingaporeSingapore
| | | | - Chul Hwan Bang
- Department of DermatologySeoul St. Mary's Hospital, College of Medicine, the Catholic University of KoreaSeoulRepublic of Korea
| | - Maria Lorna Frez
- Department of DermatologySt Luke's Medical CenterQuezon CityPhilippines
| | - Huang Yu Huei
- Department of DermatologyChang Gung Memorial HospitalTaipeiTaiwan
- School of Medicine, Chang Gung UniversityTaipeiTaiwan
| | - Doanh Le Huu
- National Hospital of Dermatology and VenereologyHanoiVietnam
| | - Tae‐Gyun Kim
- Department of DermatologyCutaneous Biology Research Institute, Severance Hospital, Yonsei University College of MedicineSeoulRepublic of Korea
| | - Akimichi Morita
- Department of Geriatric and Environmental DermatologyNagoya City University Graduate School of Medical SciencesNagoya467‐8601Japan
| | - Hazel H. Oon
- National Skin Centre and Skin Research Institute of Singapore (SRIS)SingaporeSingapore
- Yong Loo Lin School of Medicine, National University of SingaporeSingaporeSingapore
| | - Pablo Fernández‐Peñas
- Department of DermatologyWestmead HospitalWestmeadNew South WalesAustralia
- Sydney Medical School, Faculty of Medicine and Health, the University of SydneyWestmeadNew South WalesAustralia
| | - Natta Rajatanavin
- Phototherapy Unit, Division of Dermatology, Department of MedicineRamathibodi Hospital, Mahidol UniversityBangkokThailand
| | | | - Latha Selvarajah
- Department of DermatologySultan Ismail HospitalJohor BahruMalaysia
| | - Tsen‐Fang Tsai
- Department of DermatologyNational Taiwan University HospitalTaipeiTaiwan
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13
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Torres T, Antunes J, Brasileiro A, Alves J, Bernardo D, Ramos J, Sousa D, Castro C, Gusmão Palmeiro A, Aparício Martins A, Fazendeiro Matos J, Vieira Granja B, Ponte P, Marques Pinto G, Quirino P, Menezes Brandão F, Teixeira L, Magina S, Paiva Lopes MJ, Oliveira H, Varela P, Telles Sousa J, Filipe P, Tavares Bello R. Clinical course and disease burden of patients with generalized pustular psoriasis in Portugal: a multicenter retrospective cohort study. J DERMATOL TREAT 2024; 35:2345728. [PMID: 38684228 DOI: 10.1080/09546634.2024.2345728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 04/08/2024] [Indexed: 05/02/2024]
Abstract
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.
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Affiliation(s)
- Tiago Torres
- Department of Dermatology, CAC ICBAS-CHP - Centro Académico Clínico ICBAS - CHP, Porto, Portugal
- UMIB - Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
| | - Joana Antunes
- Department of Dermatology, Unidade Local de Saúde de Santa Maria, Lisboa, Portugal
| | - Ana Brasileiro
- CRI de Dermatovenereologia, Hospital de Santo António dos Capuchos, ULS São José, Lisboa, Portugal
| | - João Alves
- Department of Dermatology, Unidade Local de Saúde Almada-Seixal, Lisboa, Portugal
| | - Diana Bernardo
- Department of Dermatology, CAC ICBAS-CHP - Centro Académico Clínico ICBAS - CHP, Porto, Portugal
| | - José Ramos
- Department of Dermatology, Unidade Local de Saúde Almada-Seixal, Lisboa, Portugal
| | - Diogo Sousa
- Department of Dermatology, Unidade Local de Saúde de Santa Maria, Lisboa, Portugal
| | - Cristina Castro
- Department of Dermatology, Unidade Local de Saúde de Lisboa Ocidental, Lisboa, Portugal
| | - Ana Gusmão Palmeiro
- Department of Dermatology, Unidade Local de Saúde de Lisboa Ocidental, Lisboa, Portugal
| | | | | | - Bárbara Vieira Granja
- Department of Dermatology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Department de Biomedicine, Faculty of Medicine of Porto University, Porto, Portugal
| | - Pedro Ponte
- Department of Dermatology, Hospital da Luz Lisboa, Lisboa, Portugal
| | - Gabriela Marques Pinto
- CRI de Dermatovenereologia, Hospital de Santo António dos Capuchos, ULS São José, Lisboa, Portugal
| | - Paula Quirino
- Dentalderme Essential Aesthetics, Figueira Foz, Portugal
| | | | - Laetitia Teixeira
- Center for Health Technology and Services Research (CINTESIS), Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
| | - Sofia Magina
- Department of Dermatology, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Maria João Paiva Lopes
- CRI de Dermatovenereologia, Hospital de Santo António dos Capuchos, ULS São José, Lisboa, Portugal
| | - Hugo Oliveira
- Department of Dermatology, Unidade Local de Saúde de Coimbra, Coimbra, Portugal
| | - Paulo Varela
- Department of Dermatology, Unidade Local de Saúde de Gaia/Espinho, Porto, Portugal
| | - João Telles Sousa
- Department of Dermatology, Unidade Local de Saúde de Lisboa Ocidental, Lisboa, Portugal
| | - Paulo Filipe
- Department of Dermatology, Unidade Local de Saúde de Santa Maria, Lisboa, Portugal
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14
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Norlin JM, Löfvendahl S, Schmitt-Egenolf M. Health-related quality of life in patients with generalized pustular psoriasis - a Swedish register study. Ann Med 2024; 56:2341252. [PMID: 38738413 PMCID: PMC11095275 DOI: 10.1080/07853890.2024.2341252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 12/13/2023] [Accepted: 03/25/2024] [Indexed: 05/14/2024] Open
Abstract
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.
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Affiliation(s)
- Jenny M. Norlin
- The Swedish Institute for Health Economics (IHE), Lund, Sweden
| | - Sofia Löfvendahl
- The Swedish Institute for Health Economics (IHE), Lund, Sweden
- Department of Laboratory Medicine, Lund University, Lund, Sweden
| | - Marcus Schmitt-Egenolf
- Department of Public Health and Clinical Medicine, Dermatology, Umeå University, Umeå, Sweden
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15
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Morita A, Okubo Y, Imafuku S, Terui T. Spesolimab, the first-in-class anti-IL-36R antibody: From bench to clinic. J Dermatol 2024; 51:1379-1391. [PMID: 39373152 DOI: 10.1111/1346-8138.17449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 08/02/2024] [Accepted: 08/18/2024] [Indexed: 10/08/2024]
Abstract
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.
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Affiliation(s)
- Akimichi Morita
- Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yukari Okubo
- Department of Dermatology, Tokyo Medical University, Tokyo, Japan
| | - Shinichi Imafuku
- Department of Dermatology, Fukuoka University Faculty of Medicine, Fukuoka, Japan
| | - Tadashi Terui
- Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
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16
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Parks EA, Zaino ML, Trettin B, Feldman SR. Qualitative investigation of disease course, characteristics and lived experience of generalized pustular psoriasis. Clin Exp Dermatol 2024; 49:1362-1366. [PMID: 38739726 DOI: 10.1093/ced/llae194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 04/09/2024] [Accepted: 05/05/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND Generalized pustular psoriasis (GPP) is a relapsing-remitting chronic disease characterized by painful pustules with systemic symptoms that has a negative impact on quality of life. The psychosocial and economic burden of this rare condition is not well characterized. OBJECTIVES To qualitatively characterize the cumulative burden of GPP on patients' quality of life and psychosocial wellbeing. METHODS A retrospective chart review of patients with GPP was performed to collect demographic information, followed by prospective semistructured clinical interviews. Interview transcripts were analysed using thematic analysis. RESULTS Three major themes were revealed: (i) burden of having a chronic disease with an unpredictable course, (ii) an inability to fulfil societal roles results in a loss of identity, and (iii) a physician-patient relationship grounded in trust and transparency can be invaluable in helping patients endure chronic disease. CONCLUSIONS GPP has a negative impact on patients' quality of life and psychosocial wellbeing. Impairments in daily function and mental health primarily affect patients during flares and influence behaviour during periods of quiescence. A strong patient-physician relationship may help mitigate the impact of GPP.
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Affiliation(s)
- Emily A Parks
- East Carolina University Brody School of Medicine, Greenville, NC, USA
| | - Mallory L Zaino
- Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Bettina Trettin
- Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark
- Clinical Institute, Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Steven R Feldman
- Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC, USA
- Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark
- Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA
- Department of Social Sciences & Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA
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17
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Proft F, Duran TI, Ghoreschi K, Pleyer U, Siegmund B, Poddubnyy D. Treatment strategies for Spondyloarthritis: Implementation of precision medicine - Or "one size fits all" concept? Autoimmun Rev 2024; 23:103638. [PMID: 39276959 DOI: 10.1016/j.autrev.2024.103638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/05/2024] [Accepted: 09/07/2024] [Indexed: 09/17/2024]
Abstract
Spondyloarthritis (SpA) is a term to describe a group of chronic inflammatory rheumatic diseases, which have common pathophysiological, genetic, and clinical features. Under the umbrella term SpA, two main groups are subsumed: axial SpA (radiographic axSpA and non-radiographic axSpA) and peripheral SpA (with the leading representative being psoriatic arthritis (PsA) but also arthritis associated with inflammatory bowel disease (IBD), reactive arthritis, and undifferentiated pSpA). The key clinical symptom in axSpA is chronic back pain, typically with inflammatory characteristics, which starts in early adulthood, while the leading clinical manifestations of peripheral SpA (pSpA) are arthritis, enthesitis, and/or dactylitis. Furthermore, extra-musculoskeletal manifestations (EMMs) (acute anterior uveitis, psoriasis, and IBD) can accompany axial or peripheral symptoms. All these factors need to be taken into account when making treatment decisions in SpA patients. Despite the major advances in the treatment landscape over the past two decades with the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and most recently targeted synthetic DMARDs (tsDMARDs), a relevant proportion of patients still does not achieve the desired state of remission (=absence of disease activity). With this implementation of new treatment modalities, clinicians now have more choices to make in the treatment algorithms. However, despite generalized treatment recommendations, all factors need to be carefully considered when deciding on the optimal treatment strategy for an individual patient in clinical practice, aiming at an important first step towards personalized treatment strategies in SpA. In this narrative review, we focus on the efficacy of approved and emerging treatment options in axSpA and PsA as the main representative of pSpA and discuss their selective effect on the different manifestations associated with SpA to provide guidance on drivers of treatment decisions in specific situations.
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Affiliation(s)
- Fabian Proft
- Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
| | - Tugba Izci Duran
- Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Clinic of Rheumatology, Denizli State Hospital, Denizli, Turkey
| | - Kamran Ghoreschi
- Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Uwe Pleyer
- Department of Ophthalmology Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin; Berlin, Germany and (5)Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Britta Siegmund
- Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Denis Poddubnyy
- Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Epidemiology unit, German Rheumatism Research Centre, Berlin, Germany; Division of Rheumatology, Department of Medicine, University Health Network and University of Toronto, Toronto, Canada
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Sugiura K, Fujita H, Komine M, Yamanaka K, Akiyama M. The role of interleukin-36 in health and disease states. J Eur Acad Dermatol Venereol 2024; 38:1910-1925. [PMID: 38779986 DOI: 10.1111/jdv.19935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 01/29/2024] [Indexed: 05/25/2024]
Abstract
The interleukin (IL)-1 superfamily upregulates immune responses and maintains homeostasis between the innate and adaptive immune systems. Within the IL-1 superfamily, IL-36 plays a pivotal role in both innate and adaptive immune responses. Of the four IL-36 isoforms, three have agonist activity (IL-36α, IL-36β, IL-36γ) and the fourth has antagonist activity (IL-36 receptor antagonist [IL-36Ra]). All IL-36 isoforms bind to the IL-36 receptor (IL-36R). Binding of IL-36α/β/γ to the IL-36R recruits the IL-1 receptor accessory protein (IL-1RAcP) and activates downstream signalling pathways mediated by nuclear transcription factor kappa B and mitogen-activated protein kinase signalling pathways. Antagonist binding of IL-36Ra to IL-36R inhibits recruitment of IL-1RAcP, blocking downstream signalling pathways. Changes in the balance within the IL-36 cytokine family can lead to uncontrolled inflammatory responses throughout the body. As such, IL-36 has been implicated in numerous inflammatory diseases, notably a type of pustular psoriasis called generalized pustular psoriasis (GPP), a chronic, rare, potentially life-threatening, multisystemic skin disease characterised by recurrent fever and extensive sterile pustules. In GPP, IL-36 is central to disease pathogenesis, and the prevention of IL-36-mediated signalling can improve clinical outcomes. In this review, we summarize the literature describing the biological functions of the IL-36 pathway. We also consider the evidence for uncontrolled activation of the IL-36 pathway in a wide range of skin (e.g., plaque psoriasis, pustular psoriasis, hidradenitis suppurativa, acne, Netherton syndrome, atopic dermatitis and pyoderma gangrenosum), lung (e.g., idiopathic pulmonary fibrosis), gut (e.g., intestinal fibrosis, inflammatory bowel disease and Hirschsprung's disease), kidney (e.g., renal tubulointerstitial lesions) and infectious diseases caused by a variety of pathogens (e.g., COVID-19; Mycobacterium tuberculosis, Pseudomonas aeruginosa, Streptococcus pneumoniae infections), as well as in cancer. We also consider how targeting the IL-36 signalling pathway could be used in treating inflammatory disease states.
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Affiliation(s)
- Kazumitsu Sugiura
- Department of Dermatology, Fujita Health University School of Medicine, Toyoake, Japan
| | - Hideki Fujita
- Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Mayumi Komine
- Department of Dermatology, Faculty of Medicine, Jichi Medical University, Tochigi, Japan
| | - Keiichi Yamanaka
- Department of Dermatology, Graduate School of Medicine, Mie University, Tsu, Japan
| | - Masashi Akiyama
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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19
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Puig L, Fujita H, Thaçi D, Zheng M, Hernandez Daly AC, Leonardi C, Lebwohl MG, Barker J. Current Treatments for Generalized Pustular Psoriasis: A Narrative Summary of a Systematic Literature Search. Dermatol Ther (Heidelb) 2024; 14:2331-2378. [PMID: 39088126 PMCID: PMC11393368 DOI: 10.1007/s13555-024-01230-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 07/02/2024] [Indexed: 08/02/2024] Open
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.
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Affiliation(s)
- Lluís Puig
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
| | | | | | - Min Zheng
- Department of Dermatology, School of Medicine, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China
| | | | | | - Mark G Lebwohl
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jonathan Barker
- St. John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK
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Abboud E, Chrayteh D, Boussetta N, Dalle H, Malerba M, Wu TD, Le Gall M, Reelfs O, Pourzand C, Mellett M, Assan F, Bachelez H, Poupon J, Aractingi S, Vaulont S, Sohier P, Oules B, Karim Z, Peyssonnaux C. Skin hepcidin initiates psoriasiform skin inflammation via Fe-driven hyperproliferation and neutrophil recruitment. Nat Commun 2024; 15:6718. [PMID: 39112467 PMCID: PMC11306357 DOI: 10.1038/s41467-024-50993-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 07/23/2024] [Indexed: 08/10/2024] Open
Abstract
Psoriasis is a multifactorial, chronic inflammatory skin disease with unresolved questions on its primary events. Iron overload has been described in the epidermis of psoriasis patients, but its relevance remains unknown. We found that the key iron regulatory hormone hepcidin was highly expressed in the epidermis of psoriasis patients, especially the pustular variants resistant to treatments. In a murine model of acute skin inflammation, keratinocyte-derived hepcidin was required for iron retention in keratinocytes, leading to hyperproliferation of the epidermal layer and neutrophil recruitment, two main features of psoriatic skin lesions. Keratinocytes overexpressing hepcidin were sufficient to elicit these psoriasiform features in a transgenic mouse model. Furthermore, transcriptome analysis of these keratinocytes revealed canonical pathways found in human psoriasis, pointing to a causal role for hepcidin in the pathogenesis of the disease. Altogether, our data suggest that hepcidin could be an actionable target for skin psoriasis treatment, in addition to current therapeutics, or targeted as maintenance therapy during remission to prevent recurrence.
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Affiliation(s)
- Elise Abboud
- Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Laboratory of Excellence GR-Ex, Paris, France
| | - Doha Chrayteh
- Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Laboratory of Excellence GR-Ex, Paris, France
| | - Nadia Boussetta
- Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Laboratory of Excellence GR-Ex, Paris, France
| | - Héloise Dalle
- Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Laboratory of Excellence GR-Ex, Paris, France
| | - Mariangela Malerba
- Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Laboratory of Excellence GR-Ex, Paris, France
| | - Ting-Di Wu
- Institut Curie, PSL University, Université Paris-Saclay, CNRS UAR2016, Inserm US43, Multimodal Imaging Center, Orsay, France
| | - Morgane Le Gall
- Proteom'IC facility, Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
| | - Olivier Reelfs
- Department of Life Sciences, University of Bath, Bath, United Kingdom
| | - Charareh Pourzand
- Department of Life Sciences, University of Bath, Bath, United Kingdom
- Medicines Development, Centre for Therapeutic Innovation, University of Bath, Bath, United Kingdom
| | - Mark Mellett
- Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Zürich, Switzerland
| | - Florence Assan
- Laboratory of Genetic Skin Diseases, INSERM U1163, Imagine Institute, Université Paris Cité, Paris, France
| | - Hervé Bachelez
- Laboratory of Genetic Skin Diseases, INSERM U1163, Imagine Institute, Université Paris Cité, Paris, France
- Department of Dermatology, Hôpital Saint-Louis APHP, Université Paris Cité, Paris, France
| | - Joël Poupon
- Laboratoire de Toxicologie Biologique, Hôpital Lariboisière, Paris, France. Assistance Publique - Hôpitaux de Paris, AP-HP, Paris, France
| | - Selim Aractingi
- Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Service de Dermatologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Sophie Vaulont
- Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Laboratory of Excellence GR-Ex, Paris, France
| | - Pierre Sohier
- Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Department of Pathology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, AP-HP. Centre-Université Paris Cité, Paris, France
| | - Bénédicte Oules
- Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France
- Service de Dermatologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Zoubida Karim
- Université de Toulouse, INSERM, CNRS, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Paul Sabatier (UPS), Toulouse, France
| | - Carole Peyssonnaux
- Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France.
- Laboratory of Excellence GR-Ex, Paris, France.
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21
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Wolf P, Ceovic R, Conrad C, Falkensteiner K, Graier T, Kołt-Kamińska M, Marovt M, Mateeva V, Maul JT, Navarini AA, Nicolescu AC, Ratzinger G, Pavlovsky L, Sanzharovskaya M, Szegedi A, Reich A. Characteristics and management of generalized pustular psoriasis (GPP): Experience from the Central and Eastern Europe (CEE) GPP Expert Network. J Eur Acad Dermatol Venereol 2024; 38:1531-1542. [PMID: 38279888 DOI: 10.1111/jdv.19808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 12/06/2023] [Indexed: 01/29/2024]
Abstract
BACKGROUND Generalized pustular psoriasis (GPP) is a rare, inflammatory skin disease characterized by widespread eruption of sterile pustules with or without systemic symptoms. OBJECTIVES This study aimed to describe the demographics of patients with GPP in Central and Eastern Europe (CEE), present the clinical characteristics of individual GPP flares and explore the current treatment landscape. METHODS Patient demographics were collected at the times of last observation and previous treatment. Characteristics of a patient's last (most recent) and most severe (from all documented episodes) flare were provided at clinician's discretion. RESULTS Fifty-eight patients were recruited from 12 centres in nine CEE countries; median (range) age was 61 (16-92) years and 60.3% (35 out of 58) were female. The most common comorbidities were hypertension (43.1% [25 out of 58]) and hyperlipidaemia (32.8% [19 out of 58]). Thirty-four patients (58.6%) presented with concomitant plaque psoriasis before or during the course of GPP. Data from two separate flares were recorded in 26 individuals; in 32 patients, the most recent flare was reported as the most severe. Over 90% of patients with a flare episode classified as most severe by clinicians were hospitalized, with >75% of these individuals having a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 3 or 4. Systemic symptoms were more common in patients with a GPPGA score of 3 or 4 but were also manifest in individuals with a GPPGA score ≤2. A significant correlation was observed between a combined systemic disease score of clinical and laboratory features and both GPPGA total score (r = 0.385, p < 0.001) and GPPGA pustulation subscore (r = 0.305, p < 0.05). CONCLUSIONS Considerable heterogeneity in the presentation of GPP flares was observed, both between patients and within-patient. All GPP flares were associated with a significant clinical burden, highlighting the unmet need for accurate and early diagnosis.
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Affiliation(s)
- P Wolf
- Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria
| | - R Ceovic
- Department of Dermatology and Venereology, School of Medicine University of Zagreb, University Hospital Centre Zagreb, Zagreb, Croatia
| | - C Conrad
- Department of Dermatology, Lausanne University Hospital, Lausanne, Switzerland
| | - K Falkensteiner
- Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria
| | - T Graier
- Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria
| | - M Kołt-Kamińska
- Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszów University, Rzeszów, Poland
| | - M Marovt
- Department of Dermatology, University Medical Centre Maribor, Maribor, Slovenia
| | - V Mateeva
- Department of Dermatology, Medical University of Sofia, Sofia, Bulgaria
| | - J-T Maul
- Department of Dermatology, University Hospital of Zürich, Zürich, Switzerland
- Faculty of Medicine, University of Zürich, Zürich, Switzerland
| | - A A Navarini
- Department of Dermatology, University Hospital of Basel, Basel, Switzerland
| | - A C Nicolescu
- Emergency Clinical Hospital Agrippa Ionescu, Bucharest, Romania
| | - G Ratzinger
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria
| | - L Pavlovsky
- Division of Dermatology, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel
| | | | - A Szegedi
- Department of Dermatology, University of Debrecen, Debrecen, Hungary
| | - A Reich
- Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszów University, Rzeszów, Poland
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Lu CW, Tseng CY, Wang CW, Lin SH, Chen CB, Hui RCY, Chi CC, Huang YH, Lee CH, Lin FJ, Chung WH. Clinical Characteristics and Disease Burden of Patients with Moderate-to-Severe Generalized Pustular Psoriasis Flares in Taiwan. Dermatol Ther (Heidelb) 2024; 14:2261-2275. [PMID: 39078583 PMCID: PMC11333409 DOI: 10.1007/s13555-024-01228-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 07/02/2024] [Indexed: 07/31/2024] Open
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.
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Affiliation(s)
- Chun-Wei Lu
- Department of Dermatology, Drug Hypersensitivity, Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, No. 5, Fuxing St, Guishan District, Taoyuan, 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
| | - Chien-Yu Tseng
- Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chuang-Wei Wang
- Department of Dermatology, Drug Hypersensitivity, Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, No. 5, Fuxing St, Guishan District, Taoyuan, 333, Taiwan
- Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan
- Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou, Taiwan
- Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China
| | - Shang-Hung Lin
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Dermatology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chun-Bing Chen
- Department of Dermatology, Drug Hypersensitivity, Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, No. 5, Fuxing St, Guishan District, Taoyuan, 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan
- Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou, Taiwan
- Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan
- Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Rosaline Chung-Yee Hui
- Department of Dermatology, Drug Hypersensitivity, Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, No. 5, Fuxing St, Guishan District, Taoyuan, 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Dermatology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ching-Chi Chi
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Dermatology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Yu-Huei Huang
- Department of Dermatology, Drug Hypersensitivity, Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, No. 5, Fuxing St, Guishan District, Taoyuan, 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Dermatology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chih-Hung Lee
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Dermatology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Fang-Ju Lin
- Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan
| | - Wen-Hung Chung
- Department of Dermatology, Drug Hypersensitivity, Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, No. 5, Fuxing St, Guishan District, Taoyuan, 333, Taiwan.
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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23
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Gwillim EC, Nichols AJ. Spesolimab for generalized pustular psoriasis: a review of two key clinical trials supporting initial US regulatory approval. Front Immunol 2024; 15:1359481. [PMID: 39104539 PMCID: PMC11298804 DOI: 10.3389/fimmu.2024.1359481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 06/13/2024] [Indexed: 08/07/2024] Open
Abstract
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<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.
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Affiliation(s)
- Eran C. Gwillim
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, United States
- Jackson Health System, Miami, FL, United States
| | - Anna J. Nichols
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, United States
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Puig L, Izu Belloso R, Rivera-Díaz R, Mollet Sánchez J, Rodríguez Fernández-Freire L, Sahuquillo-Torralba A, Ruiz-Villaverde R. A Non-Interventional, Multicenter Study to Characterize the Socio-Demographics, Clinical Characteristics, and Management of Generalized Pustular Psoriasis Patients in Spain: IMPULSE Study. Dermatology 2024; 240:778-792. [PMID: 39019021 PMCID: PMC11651324 DOI: 10.1159/000540019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 06/24/2024] [Indexed: 07/19/2024] Open
Abstract
INTRODUCTION Generalized pustular psoriasis (GPP) is a chronic, rare, and potentially life-threatening skin condition characterized by flares comprising widespread sterile pustules and systemic inflammation. Both the rarity and heterogeneity of the disease have made GPP classification and standardization of clinical criteria challenging. Before the approval of spesolimab (IL-36R antibody) in 2022, there were no approved treatments in the USA or Europe for GPP flares. Treatment for GPP has amounted to off-label use of medicines approved to treat plaque psoriasis. Our aim was to describe the sociodemographics, clinical characteristics, and treatment patterns of patients with GPP in Spain. METHODS Non-interventional, descriptive, multi-center, retrospective chart review of patients diagnosed with GPP in Spain. RESULTS 56 patients (50% women) were included, with a mean (standard deviation, SD) age at diagnosis of 53.7 (20.5) and a mean (SD) time of follow-up of 3.7 (3.1) years. In 80% of patients, GPP diagnosis was associated with a flare and 67.3% had known risk factors for GPP (such as previous diagnosis or family history of plaque psoriasis, comorbidities, smoking or stress). Hypertension and plaque psoriasis were the most frequent comorbidities (44.6% each). The number of GPP flares per patient-year was 0.55 with (range 0-4) a mean (SD) body surface area involvement of 21.3% (19.1). The most frequent manifestations of GPP flares were pustules (88.5%), erythema (76.9%), and scaling (76.9%). Additionally, 65.4% of patients had plaque psoriasis, 53.8% had unspecified skin lesions, and 30.8% experienced pain. The treatments used for GPP flares were off-label conventional systemic drugs (75%), mostly corticosteroids, cyclosporine, and acitretin. In the periods between flares, off-label biologics were used in 56.5% of patients. During the study period, 9 patients (16.1%) had at least one complication and 5 of them required hospitalization. CONCLUSION This is the first multicenter study in Spanish GPP patients. Most patients were in their fifties, with personal or family history of plaque psoriasis, stress, smoking and a wide range of comorbidities and complications. Even though the number of flares per patient/year was 0.55, there was variability between patients. Both off-label conventional systemics and off-label biologics were used for flare management without a clear treatment pattern.
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Affiliation(s)
- Lluís Puig
- Dermatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Rosa Izu Belloso
- Dermatology Department, Hospital Universitario Basurto, Bilbao, Spain
| | - Raquel Rivera-Díaz
- Dermatology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
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Burden AD, Bissonnette R, Anatchkova M, Budhiarso I, Skalicky AM, Liberato ACS, Hu N, Thoma C, Gloede T, Kohlmann T, Lebwohl MG. Psychometric validation of the Psoriasis Symptom Scale, Functional Assessment of Chronic Illness Therapy-Fatigue and pain-Visual Analogue Scale in patients with generalized pustular psoriasis. J Eur Acad Dermatol Venereol 2024; 38:1383-1390. [PMID: 38334243 DOI: 10.1111/jdv.19830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 01/19/2024] [Indexed: 02/10/2024]
Abstract
BACKGROUND Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease associated with considerable patient burden. The Psoriasis Symptom Scale (PSS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and pain-Visual Analogue Scale (pain-VAS) are patient-reported outcomes (PROs) that have not yet been validated in patients with GPP. OBJECTIVES To evaluate the psychometric properties of the PSS, FACIT-Fatigue and pain-VAS using data from Effisayil 1, a randomised trial of spesolimab in patients with moderate-to-severe GPP. METHODS Inter-item correlations and confirmatory factor analysis (CFA) were performed using Week 1 data. Internal consistency was assessed with Cronbach's α coefficient using baseline and Week 1 data. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs); change data for the GPP Physician Global Assessment total score and pustulation subscore were used to define a stable population. Convergent validity was assessed at baseline and Week 1 using Spearman's rank-order correlations. Known-groups validity was measured by analysis of variance using Week 1 data. Ability to detect change from baseline to Week 1 was evaluated by analysis of covariance. RESULTS Inter-item and item-to-total correlations were moderate or strong for most PSS and FACIT-Fatigue items. CFA demonstrated the unidimensionality of the PSS and FACIT-Fatigue, with high factor loadings for most items (PSS range, 0.75-0.94; FACIT-Fatigue range, 0.11-0.93) and acceptable fit statistics. Both scores demonstrated internal consistency (Cronbach's α, 0.71 and 0.95, respectively). The PSS, FACIT-Fatigue and pain-VAS demonstrated test-retest reliability (ICCs ≥0.70) and good evidence of convergent validity. Furthermore, the PROs could differentiate between known groups of varying symptom severity (range, p < 0.0001-0.0225) and detect changes in symptom severity from baseline to Week 1 (range, p < 0.0001-0.0002). CONCLUSIONS Overall, these results support the reliability, validity and ability to detect change of the PSS, FACIT-Fatigue and pain-VAS as PROs in patients with GPP.
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Affiliation(s)
- A David Burden
- School of Infection and Immunity, University of Glasgow, Glasgow, UK
| | | | | | | | | | | | - Na Hu
- Boehringer Ingelheim (China) Investment Co. Ltd, Shanghai, China
| | | | - Tristan Gloede
- Boehringer Ingelheim International GmbH, Ingelheim, Germany
| | - Thomas Kohlmann
- Institute for Community Medicine, Medical University Greifswald, Greifswald, Germany
| | - Mark G Lebwohl
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
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26
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Teshima R, Saito-Sasaki N, Sawada Y. Generalized Pustular Psoriasis and Systemic Organ Dysfunctions. Int J Mol Sci 2024; 25:6270. [PMID: 38892457 PMCID: PMC11172751 DOI: 10.3390/ijms25116270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 06/02/2024] [Accepted: 06/04/2024] [Indexed: 06/21/2024] Open
Abstract
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.
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Affiliation(s)
| | | | - Yu Sawada
- Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
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27
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Feldman SR, Bohn RL, Gao R, Gray S, Walton SE, Déruaz-Luyet A, Wu JJ. Poor adherence to and persistence with biologics in generalized pustular psoriasis: A claim-based study using real-world data from two large US databases. JAAD Int 2024; 15:78-83. [PMID: 38440298 PMCID: PMC10910301 DOI: 10.1016/j.jdin.2023.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/19/2023] [Indexed: 03/06/2024] Open
Abstract
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.
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Affiliation(s)
- Steven R. Feldman
- Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | | | - Ran Gao
- Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut
| | | | | | | | - Jashin J. Wu
- Department of Dermatology, University of Miami, Miller School of Medicine, Miami, Florida
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28
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Viguier M, Bentayeb M, Azzi J, de Pouvourville G, Gloede T, Langellier B, Massol J, Medina P, Thoma C, Bachelez H. Generalized pustular psoriasis: A nationwide population-based study using the National Health Data System in France. J Eur Acad Dermatol Venereol 2024; 38:1131-1139. [PMID: 38404163 DOI: 10.1111/jdv.19901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 01/24/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND GPP is a rare, chronic, neutrophilic skin disease, with limited real-world data characterizing patients with flares and the impact of flares on disease progression and morbidity. OBJECTIVE Describe the clinical characteristics of patients with GPP, comorbidities, disease epidemiology and frequency and severity of flares, and compare patients with GPP with a matched severe psoriasis population. METHODS In this population-based real-world cohort study an algorithm was developed to identify patients with GPP flares. Three cohorts were identified using the Système National des Données de Santé (SNDS) database covering almost the entire French population; a prevalent cohort (2010-2018), an incident cohort (2012-2015). A severe psoriasis cohort was compared with the GPP incident cohort using propensity score matching. RESULTS The prevalent and incident cohorts comprised 4195 and 1842 patients, respectively. In both cohorts, mean age was 58 years; 53% were male. Comorbidities were significantly more common in the incident cohort versus matched psoriasis cohort, respectively, including hypertension (44% vs. 26%), ischaemic heart disease (26% vs. 18%) and hyperlipidaemia (25% vs. 15%). In the incident cohort, the flare rate was 0.1 flares/person-year and 0.4 flares/person-year among the 569 out of 1842 patients hospitalized with flares. These patients had a mean (±SD) stay of 11.6 ± 10.4 days; 25% were admitted to the intensive care unit. In 2017, the cumulative incidence and cumulative GPP age-sex standardized prevalence were 7.1 and 45.2 per million, respectively. CONCLUSIONS Patients with GPP had a distinct comorbidity profile compared to patients with severe psoriasis, and GPP flares were associated with long hospitalizations.
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Affiliation(s)
- Manuelle Viguier
- Department of Dermatology-Venereology, Hôpital Robert Debré and Université Reims-Champagne Ardenne, IRMAIC, EA 7509, Reims, France
| | | | | | | | - Tristan Gloede
- Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut, USA
| | | | - Jacques Massol
- Aixial Consulting, Boulogne Billancourt, France
- Remede Consulting Group, Paris, France
| | | | | | - Hervé Bachelez
- Service de Dermatologie, Assistance Publique-Hôpitaux de Paris Hôpital Saint-Louis, and INSERM Unité 1163, Imagine Institute of Genetic Diseases, Université Paris Cité, Paris, France
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29
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Feldman SR, Gao R, Bohn RL, Gray S, Walton SE, Déruaz-Luyet A, Wu JJ. Varied treatment pathways with no defined treatment sequencing in patients with generalized pustular psoriasis: A claims-based study. JAAD Int 2024; 15:59-61. [PMID: 38371664 PMCID: PMC10869926 DOI: 10.1016/j.jdin.2023.11.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2024] Open
Affiliation(s)
- Steven R. Feldman
- Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Ran Gao
- Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut
| | | | | | | | | | - Jashin J. Wu
- Department of Dermatology, University of Miami, Miller School of Medicine, Miami, Florida
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30
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Parasramani SG, Kar BR, Tahiliani S, Parthasarathi A, Neema S, Ganguly S, Sathishkumar D, Venkatachalam K, Komeravelli H, Thomas J. Management of Pustular Psoriasis; The Way Ahead. Indian J Dermatol 2024; 69:241-248. [PMID: 39119327 PMCID: PMC11305487 DOI: 10.4103/ijd.ijd_165_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/10/2024] Open
Abstract
Pustular psoriasis is a specialized variant of psoriasis which can be life threatening if not treated at the earliest. The pathogenesis has been recently linked to the role of interleukin 36. Apart from the corticosteroids, systemic antipsoriatics like acitretin, cyclosporine and methotrexate have been used with some success though unpredictable. With recent identification of role of IL-36 in the pathogenesis of pustular psoriasis, biologics targeting the IL-36 receptors have been used to manage the situation with high degree of success. This narrative review deals with the recent concepts of pathogenesis of pustular psoriasis as well as the current management scenario.
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Affiliation(s)
| | - Bikash R. Kar
- Department of DVL, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Sushil Tahiliani
- Department of DVL, P D Hinduja Hospital and Research Centre, Mumbai, Maharashtra, India
| | | | | | | | | | | | | | - Jayakar Thomas
- Senior Consultant Dermatologist, Apollo Hospitals and KK Child Trust Hospital, Chennai, Tamil Nadu, India
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31
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Vilarrasa E, Rivera R, Eiris N, Carretero G, de la Cueva P, Carrascosa JM. [Translated article] Approach to the Epidemiology, Disease Management, and Current Challenges in the Management of Generalized Pustular Psoriasis Through a Survey Conducted Among Spanish Dermatologists. ACTAS DERMO-SIFILIOGRAFICAS 2024; 115:T449-T457. [PMID: 38479699 DOI: 10.1016/j.ad.2024.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 10/22/2023] [Indexed: 05/05/2024] Open
Abstract
BACKGROUND Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease characterised by recurrent or intermittent flares. Epidemiological and disease management data in Spain are limited. Our goal was to estimate the epidemiology of GPP, explore its management, and reach consensus on the current challenges faced in Spain. METHODS An electronic survey was submitted to dermatologists from the Spanish Academy of Dermatology and Venereology Psoriasis Working Group. This group is experienced in the management of GPP. It included a Delphi consensus to establish the current challenges. RESULTS A total of 33 dermatologists responded to the survey. A 5-year prevalence and incidence of 13.05 and 7.01 cases per million inhabitants, respectively, were estimated. According to respondents, the most common GPP symptoms are pustules, erythema, and desquamation, while 45% of patients present > 1 annual flares. A total of 45% of respondents indicated that flares often require a length of stay between 1 and 2 weeks. In the presence of a flare, 67% of respondents often or always prescribe a non-biological systemic treatment as the first-line therapy [cyclosporine (55%); oral retinoid (30%)], and 45% a biological treatment [anti-TNFα (52%); anti-IL-17 (39%)]. The dermatologists agreed that the main challenges are to define and establish specific therapeutic goals to treat the disease including the patients' perspective on the management of the disease. CONCLUSION Our study describes the current situation on the management of GPP in Spain, increasing the present knowledge on the disease, and highlighting the current challenges faced at the moment.
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Affiliation(s)
- E Vilarrasa
- Servicio de Dermatología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Universitat Autónoma de Barcelona, Barcelona, Spain.
| | - R Rivera
- Servicio de Dermatología, Hospital Universitario 12 de Octubre, Madrid, Spain; Universidad Complutense, Madrid, Spain
| | - N Eiris
- Servicio de Dermatología, Hospital Universitario Virgen Macarena, Sevilla, Spain
| | - G Carretero
- Servicio de Dermatología, Hospital Universitario de Gran Canaria Doctor Negrin, Gran Canaria, Spain
| | - P de la Cueva
- Universidad Complutense, Madrid, Spain; Servicio de Dermatología, Hospital Infanta Leonor, Madrid, Spain
| | - J M Carrascosa
- Universitat Autónoma de Barcelona, Barcelona, Spain; Servicio de Dermatología, Hospital Germans Trias i Pujol, Barcelona, Spain; Instituto de Investigación Germans Trias i Pujol (IGTP), Barcelona, Spain
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32
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Vilarrasa E, Rivera R, Eiris N, Carretero G, de la Cueva P, Carrascosa JM. Approach to the Epidemiology, Disease Management, and Current Challenges in the Management of Generalized Pustular Psoriasis Through a Survey Conducted Among Spanish Dermatologists. ACTAS DERMO-SIFILIOGRAFICAS 2024; 115:449-457. [PMID: 37925068 DOI: 10.1016/j.ad.2023.10.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 10/20/2023] [Accepted: 10/22/2023] [Indexed: 11/06/2023] Open
Abstract
BACKGROUND Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease characterised by recurrent or intermittent flares. Epidemiological and disease management data in Spain are limited. Our goal was to estimate the epidemiology of GPP, explore its management, and reach consensus on the current challenges faced in Spain. METHODS An electronic survey was submitted to dermatologists from the Spanish Academy of Dermatology and Venereology Psoriasis Working Group. This group is experienced in the management of GPP. It included a Delphi consensus to establish the current challenges. RESULTS A total of 33 dermatologists responded to the survey. A 5-year prevalence and incidence of 13.05 and 7.01 cases per million inhabitants, respectively, were estimated. According to respondents, the most common GPP symptoms are pustules, erythema, and desquamation, while 45% of patients present > 1 annual flares. A total of 45% of respondents indicated that flares often require a length of stay between 1 and 2 weeks. In the presence of a flare, 67% of respondents often or always prescribe a non-biological systemic treatment as the first-line therapy [cyclosporine (55%); oral retinoid (30%)], and 45% a biological treatment [anti-TNFα (52%); anti-IL-17 (39%)]. The dermatologists agreed that the main challenges are to define and establish specific therapeutic goals to treat the disease including the patients' perspective on the management of the disease. CONCLUSION Our study describes the current situation on the management of GPP in Spain, increasing the present knowledge on the disease, and highlighting the current challenges faced at the moment.
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Affiliation(s)
- E Vilarrasa
- Servicio de Dermatología, Hospital de la Santa Creu i Sant Pau, Barcelona, España; Universitat Autónoma de Barcelona, Barcelona, España.
| | - R Rivera
- Servicio de Dermatología, Hospital Universitario 12 de Octubre, Madrid, España; Universidad Complutense, Madrid, España
| | - N Eiris
- Servicio de Dermatología, Hospital Universitario Virgen Macarena, Sevilla, España
| | - G Carretero
- Servicio de Dermatología, Hospital Universitario de Gran Canaria Doctor Negrin, Gran Canaria, España
| | - P de la Cueva
- Universidad Complutense, Madrid, España; Servicio de Dermatología, Hospital Infanta Leonor, Madrid, España
| | - J M Carrascosa
- Universitat Autónoma de Barcelona, Barcelona, España; Servicio de Dermatología, Hospital Germans Trias i Pujol, Barcelona, España; Instituto de Investigación Germans Trias i Pujol (IGTP), Barcelona, España
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33
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Cramer N, Buhl T, Schön MP, Mössner R. Erste Episode einer generalisierten pustulösen Psoriasis oder akute generalisierte exanthematische Pustulose? Eine Fallstudie. J Dtsch Dermatol Ges 2024; 22:693-695. [PMID: 38730514 DOI: 10.1111/ddg.15332_g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 11/15/2023] [Indexed: 05/13/2024]
Affiliation(s)
- Neda Cramer
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Göttingen
| | - Timo Buhl
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Göttingen
| | - Michael P Schön
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Göttingen
| | - Rotraut Mössner
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Göttingen
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34
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Teshima R, Saito-Sasaki N, Hitaka T, Sawada Y. Spesolimab in the Management of Generalized Pustular Psoriasis With Concurrent Bullous Pemphigoid and Psoriasis. Cureus 2024; 16:e60331. [PMID: 38883056 PMCID: PMC11177237 DOI: 10.7759/cureus.60331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/14/2024] [Indexed: 06/18/2024] Open
Abstract
Autoimmune diseases often co-occur due to shared immunological mechanisms, necessitating strategic treatment approaches to manage overlapping conditions without exacerbating each other. A 75-year-old male with a history of psoriasis vulgaris and bullous pemphigoid (BP) developed new-onset pustular psoriasis under systemic corticosteroid therapy, which is known to potentially worsen psoriasis into its pustular form. Histological examination confirmed the diagnosis, showing features typical of pustular psoriasis. The patient was successfully treated with spesolimab, an anti-IL-36 neutralizing antibody, achieving complete remission without aggravating the BP. This case highlights the necessity of cautious treatment selection in patients with multiple autoimmune disorders and underscores the potential role of IL-36 in exacerbating inflammatory responses in BP. Further research into the interaction between IL-36 and BP may provide deeper insights into managing such complex clinical scenarios.
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Affiliation(s)
- Romane Teshima
- Dermatology, University of Occupational and Environmental Health, Kitakyushu, JPN
| | - Natsuko Saito-Sasaki
- Dermatology, University of Occupational and Environmental Health, Kitakyushu, JPN
| | - Taiyo Hitaka
- Dermatology, University of Occupational and Environmental Health, Kitakyushu, JPN
| | - Yu Sawada
- Dermatology, University of Occupational and Environmental Health, Kitakyushu, JPN
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35
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Cramer N, Buhl T, Schön MP, Mössner R. First episode of generalized pustular psoriasis or acute generalized exanthematous pustulosis? A case study. J Dtsch Dermatol Ges 2024; 22:693-695. [PMID: 38487968 DOI: 10.1111/ddg.15332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 11/15/2023] [Indexed: 05/12/2024]
Affiliation(s)
- Neda Cramer
- Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany
| | - Timo Buhl
- Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany
| | - Michael P Schön
- Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany
| | - Rotraut Mössner
- Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany
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36
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Hayama K, Tian Y, Iwasaki R, Fujita H. Patient Journey of Generalized Pustular Psoriasis: A Real-world Study Using Data-mining Methods and Japanese Claims Data. Acta Derm Venereol 2024; 104:adv11946. [PMID: 38629892 DOI: 10.2340/actadv.v104.11946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 12/12/2023] [Indexed: 04/19/2024] Open
Abstract
Abstract is missing (Short communication)
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Affiliation(s)
- Koremasa Hayama
- Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Yahui Tian
- Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
| | | | - Hideki Fujita
- Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
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37
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Armstrong AW, Elston CA, Elewski BE, Ferris LK, Gottlieb AB, Lebwohl MG. Generalized pustular psoriasis: A consensus statement from the National Psoriasis Foundation. J Am Acad Dermatol 2024; 90:727-730. [PMID: 37838256 DOI: 10.1016/j.jaad.2023.09.080] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 09/11/2023] [Accepted: 09/24/2023] [Indexed: 10/16/2023]
Affiliation(s)
- April W Armstrong
- Division of Dermatology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, California.
| | - Carly A Elston
- Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Boni E Elewski
- Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Laura K Ferris
- Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Alice B Gottlieb
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Mark G Lebwohl
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York
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Gössinger E, Dodiuk-Gad R, Mühleisen B, Oon HH, Oh CC, Maul JT, Navarini AA. Generalized Pustular Psoriasis, Acute Generalized Exanthematous Pustulosis, and Other Pustular Reactions: A Clinical Review. Dermatol Clin 2024; 42:317-328. [PMID: 38423690 DOI: 10.1016/j.det.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2024]
Abstract
Generalized pustular rashes have various etiologies and can be challenging to diagnose and manage at first presentation. The authors provide an in-depth analysis of common pustular skin eruptions including generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis, focusing on their pathophysiology, triggers, clinical presentation, diagnostic challenges, and management strategies. The article also highlights recent advances in genetic research and biologic therapies for GPP and the future directions in personalized medicine and prevention strategies.
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Affiliation(s)
- Elisabeth Gössinger
- Department of Dermatology, University Hospital of Basel, Burgfelderstrasse 101, Basel 4055, Switzerland
| | - Roni Dodiuk-Gad
- Department of Dermatology, Emek Medical Center, Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, 3525433 Israel; Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A1, Canada
| | - Beda Mühleisen
- Department of Dermatology, University Hospital of Basel, Burgfelderstrasse 101, Basel 4055, Switzerland
| | - Hazel H Oon
- Department of Dermatology, Emek Medical Center, Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, 3525433 Israel; National Skin Centre and Skin Research Institute of Singapore (SRIS), 1 Mandalay Road, Singapore 308205, Singapore
| | - Choon Chiat Oh
- Department of Dermatology, Singapore General Hospital, Singapore, Singapore; Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore
| | - Julia-Tatjana Maul
- Department of Dermatology, University Hospital of Zurich and Faculty of Medicine, Zurich 8091/8006, Switzerland
| | - Alexander A Navarini
- Department of Dermatology, University Hospital of Basel, Burgfelderstrasse 101, Basel 4055, Switzerland; Department of Biomedical Research, University of Basel, Allschwil 4123, Switzerland; Department of Biomedical Engineering, University of Basel, Allschwil 4123, Switzerland; Department of Clinical Research, University of Basel, Allschwil 4123, Switzerland.
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Adi G, Shaath MR, Adi K, Obaid Z, Aldosari E, AlKateb FA. Generalized pustular psoriasis in a toddler with IL36RN mutation: a case report. Front Immunol 2024; 15:1337799. [PMID: 38571950 PMCID: PMC10987684 DOI: 10.3389/fimmu.2024.1337799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 02/29/2024] [Indexed: 04/05/2024] Open
Abstract
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.
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Affiliation(s)
- Ghaith Adi
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | | | - Kareem Adi
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Zaki Obaid
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Egab Aldosari
- Children’s Specialised Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Faten Ahmed AlKateb
- Children’s Specialised Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
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40
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Rega F, Trovato F, Bortone G, Pellacani G, Richetta AG, Dattola A. Therapeutic Potential of Spesolimab-Sbzo in the Management of Generalized Pustular Psoriasis Flares in Adults: Evidence to Date. PSORIASIS (AUCKLAND, N.Z.) 2024; 14:23-27. [PMID: 38505140 PMCID: PMC10950078 DOI: 10.2147/ptt.s393978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 03/06/2024] [Indexed: 03/21/2024]
Abstract
Generalized pustular psoriasis (GPP) is a rare, chronic, and severe skin disorder characterized by the eruption of non-infectious pustules on an erythematous background often associated with systemic symptoms. It may appear in association with plaque psoriasis or occur in previously healthy individuals. It differs from psoriasis vulgaris in clinical presentation, immunopathogenesis, histology, and therapeutic strategies. Overexpression of interleukin 36 (IL-36) or a loss-of-function mutation of IL-36 receptor antagonist (IL-36RA) are thought to play a pivotal role in the pathogenesis of this disease. There are currently no globally approved guidelines for the treatment of GPP, and the therapies used so far, with variable results, have given unsatisfactory results. Spesolimab, a selective humanized antibody against the IL-36 receptor that blocks its activation, is the first biologic drug approved in Europe in December 2022 for the treatment of GPP flares. It represents a promising therapy, demonstrating efficacy in reducing disease severity and improving patient outcomes. In our review, we have analyzed the latest advancements and findings regarding the efficacy and safety of spesolimab in the context of GPP management.
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Affiliation(s)
- Federica Rega
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Science, University of La Sapienza, Rome, Italy
| | - Federica Trovato
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Science, University of La Sapienza, Rome, Italy
| | - Giulio Bortone
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Science, University of La Sapienza, Rome, Italy
| | - Giovanni Pellacani
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Science, University of La Sapienza, Rome, Italy
| | - Antonio Giovanni Richetta
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Science, University of La Sapienza, Rome, Italy
| | - Annunziata Dattola
- Dermatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Science, University of La Sapienza, Rome, Italy
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41
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Merola JF, Amin AZ. Exploring the Clinical Presentation, Course, and Burden of Disease in Generalized Pustular Psoriasis [Podcast]. Clin Cosmet Investig Dermatol 2024; 17:539-545. [PMID: 38482176 PMCID: PMC10936732 DOI: 10.2147/ccid.s444221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 10/11/2023] [Indexed: 11/02/2024]
Abstract
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.
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Affiliation(s)
| | - Ahmad Z Amin
- Northwestern University Feinberg, School of Medicine, Chicago, Illinois, USA
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Fujita H, Iwasaki R, Tsuboi S, Murashiuma Y, Akiyama M. Regional differences in the prevalence of generalized pustular psoriasis in Japan. J Dermatol 2024; 51:380-390. [PMID: 38292005 PMCID: PMC11483897 DOI: 10.1111/1346-8138.17089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 11/30/2023] [Accepted: 12/11/2023] [Indexed: 02/01/2024]
Abstract
Generalized pustular psoriasis (GPP), a rare form of psoriasis, is characterized by neutrophil-rich, sterile pustules. In Japan, GPP has intractable and rare disease designation, which allows patients to access support from national and local governments for medical expenses. Previously, similar numbers of patients in Tokyo and Hokkaido have been shown to have GPP designation, despite different population sizes. Here, we determine whether there are regional differences in the proportion of patients receiving GPP designation status in Japan and aim to identify causal factors. In this descriptive, retrospective cohort study, publicly available data were collected on the number of patients with intractable and rare disease designation for GPP in each prefecture and age classification (April 2018-March 2021). Three other designated intractable and rare disease cohorts were included: pemphigus, rare skin diseases, and all diseases. The primary outcome was the standardized morbidity ratio (SMR) of patients at prefecture level (observed numbers divided by expected). Regional differences were compared with the statistical expectation for the total population and age distribution of each prefecture. Regional differences were observed in all cohorts. Overall, 1910 patients had GPP as a designated intractable and rare disease in 2020. Regional differences in SMRs for GPP were observed with high SMRs (≥1.5) in Hokkaido, Tottori, Kagawa, and Miyazaki, and low SMRs (<0.6) in Gunma and Kanagawa. Regional differences in SMRs for GPP did not correlate with the number of medical doctors or dermatologists or internal migration. The number of medical doctors or dermatologists correlated with SMRs in the rare skin diseases and total cohorts. Regional differences in Japan exist in the number of patients with GPP who have an intractable and rare disease designation. Managing rare diseases is an important public health issue, and further research is required to elucidate the factors contributing to these differences.
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Affiliation(s)
- Hideki Fujita
- Department of DermatologyNihon University School of MedicineTokyoJapan
| | | | | | | | - Masashi Akiyama
- Department of DermatologyNagoya University Graduate School of MedicineNagoyaJapan
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Yang HJ, Lee MY, Lee JH, Jung CJ, Lee WJ, Won CH, Lee MW, Jung JM, Chang SE. Comparison of metabolic and neurological comorbidities in Asian patients with psoriasis and atopic dermatitis. Sci Rep 2024; 14:4212. [PMID: 38378928 PMCID: PMC10879488 DOI: 10.1038/s41598-024-54407-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 02/12/2024] [Indexed: 02/22/2024] Open
Abstract
Although various comorbidities have been noted to be associated with atopic dermatitis (AD) and psoriasis, few studies have compared comorbidities between the two diseases, and little is known about whether these comorbidities vary by the subtypes of psoriasis. In this study of 1:1 age- and sex-matched pair analysis between patients diagnosed with either psoriasis or AD at Asan Medical Center between 1991 and 2020, comorbidities, as determined by the International Classification of Diseases-10 codes, and likelihood ratios of metabolic and neurologic comorbidities in psoriasis compared with AD were studied using a logistic regression model. Among a total of 14,128 patients, the psoriasis group had higher odds of obesity (odds ratio [95% confidence interval]: 1.49 [1.34-1.66]), hypertension (1.14 [1.03-1.26]), diabetes mellitus (1.46 [1.29-1.66]), chronic kidney disease (1.59 [1.22-2.08]), and Parkinson's disease (2.1 [1.15-3.83]) than the AD group. Subgroup analysis revealed that patients with plaque psoriasis had higher odds of obesity (1.18 [1.05-1.33]), hypertension (1.18 [1.06-1.32]), diabetes mellitus (1.53 [1.34-1.75]), chronic kidney disease (1.66 [1.26-2.17]), and Parkinson's disease (2.12 [1.16-3.88]) compared with AD. Meanwhile, guttate psoriasis was associated with higher odds of dementia (3.63 [1.06-12.40]) and patients with generalized pustular psoriasis showed higher odds of diabetes mellitus (5.42 [1.56-18.83]) compared with AD. In conclusion, Asian patients with all types of psoriasis should be closely monitored for the development of metabolic and neurologic diseases, especially men and those aged ≥ 40 years.
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Affiliation(s)
- Hee Joo Yang
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Mi Young Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Jeong Hyeon Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Republic of Korea
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea
| | - Chang Jin Jung
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Woo Jin Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Chong Hyun Won
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Mi Woo Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Joon Min Jung
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Republic of Korea.
| | - Sung Eun Chang
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Republic of Korea.
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
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Yang Z, Jin Y, Wang M, Li R, Li WQ, Li H. Enhanced impact of psoriasis severity on the treatment demands of patients during the COVID-19 pandemic: a cross-sectional study based on a national psoriasis registry in China. BMJ Open 2024; 14:e079627. [PMID: 38367975 PMCID: PMC10875510 DOI: 10.1136/bmjopen-2023-079627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 01/17/2024] [Indexed: 02/19/2024] Open
Abstract
OBJECTIVES The personalised treatment demands of patients with psoriasis did not get significant attention during the pandemic lockdown. This study aimed to investigate the treatment demands of patients with psoriasis with different severities, stratified by COVID-19 pandemic conditions. DESIGN Cross-sectional study design. SETTING Multicentre study based on a national psoriasis registry in China. PARTICIPANTS A total of 22 425 adult patients with psoriasis were enrolled between August 2020 and September 2021. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcomes were patient demands for quick healing of skin lesions and improving mental health, which were collected by questionnaires. Multivariable logistic models were used to examine the impact of disease severity, as measured by Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Investigator's Global Assessment (IGA), on treatment demands, as stratified by COVID-19 pandemic conditions (lockdown vs non-lockdown). RESULTS Increasing PASI score significantly increased patient demands for rapid healing of skin lesions and improving mental health during non-lockdown periods. The magnitude of both associations further increased during the COVID-19 lockdown from an OR of 1.45 (95% CI 1.27 to 1.65) to 2.19 (95% CI 1.57 to 3.05) and 2.21 (95% CI 2.03 to 2.40) to 2.82 (95% CI 2.24 to 3.55), respectively. The skin lesion healing demand was more triggered by the overall irritation level (measured by IGA, OR 1.64, 95% CI 1.35 to 1.99 during non-lockdown periods vs OR 2.70, 95% CI 1.63 to 4.49 during lockdowns), while the mental health improving demand was more triggered by lesion coverage (measured by BSA, OR 2.01, 95% CI 1.85 to 2.19 vs OR 3.27, 95% CI 2.57 to 4.15). CONCLUSIONS Psoriasis aggravation significantly increased patients' treatment demands, especially during lockdowns. The used psoriasis severity measures highlighted patients' treatment demands differently. This suggests more accessible and personalised healthcare for patients with psoriasis should be available during future pandemics.
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Affiliation(s)
- Zhihui Yang
- Department of Dermatology and Venerology, National Clinical Research Center for Skin and Immune Diseases, Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, and NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Peking University First Hospital, Beijing, China
| | - Yu Jin
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, and Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Mingyue Wang
- Department of Dermatology and Venerology, National Clinical Research Center for Skin and Immune Diseases, Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, and NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Peking University First Hospital, Beijing, China
| | - Ruoyu Li
- Department of Dermatology and Venerology, National Clinical Research Center for Skin and Immune Diseases, Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, and NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Peking University First Hospital, Beijing, China
| | - Wen-Qing Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, and Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hang Li
- Department of Dermatology and Venerology, National Clinical Research Center for Skin and Immune Diseases, Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, and NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Peking University First Hospital, Beijing, China
- Peking University - Yunnan Baiyao International Medical Research Center, Peking University, Beijing, China
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Choon SE, De La Cruz C, Wolf P, Jha RK, Fischer KI, Goncalves-Bradley DC, Hepworth T, Marshall SR, Gottlieb AB. Health-related quality of life in patients with generalized pustular psoriasis: A systematic literature review. J Eur Acad Dermatol Venereol 2024; 38:265-280. [PMID: 37750484 DOI: 10.1111/jdv.19530] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 09/15/2023] [Indexed: 09/27/2023]
Abstract
Generalized pustular psoriasis (GPP) is a rare, chronic, neutrophilic inflammatory skin disease characterized by episodes of widespread eruption of sterile, macroscopic pustules that can be accompanied by systemic inflammation and symptoms. A systematic literature review and narrative synthesis were conducted to determine the impact of GPP on patients' health-related quality of life (HRQoL) and patient-reported severity of symptoms and to compare its impact to patients with plaque psoriasis (plaque PsO). Searches were undertaken in Embase, MEDLINE and the Cochrane Library from 1 January 2002 to 15 September 2022. Screening was carried out by two reviewers independently. Outcome measures included generic (e.g. EQ-5D, SF-36) and dermatology-specific (e.g. DLQI) clinical outcome assessments, and other relevant patient-reported outcome measures (PROMs) (e.g. severity of pain measured by a numerical rating scale). Overall, 20 studies were found to be eligible for inclusion, of which seven also had data for plaque PsO. The DLQI was the most frequently reported outcome measure (16 out of 20 studies). When reported, mean DLQI (SD) scores varied from 5.7 (1.2) to 15.8 (9.6) across the studies, indicating a moderate to very large effect on HRQoL; the wide range of scores and large SDs were explained by the small population sizes (n ≤ 12 for all studies except two). Similar ranges and large SDs were also observed for other measures within individual studies. However, in general, people with GPP reported a greater impact of their skin condition on HRQoL, when compared to people with plaque PsO (i.e. higher DLQI scores) and higher severity for itch, pain and fatigue. This systematic review highlighted the need for studies with a larger population size, a better understanding of the impact of cutaneous and extracutaneous symptoms and comorbidities on HRQoL during and between GPP flares, and outcome measures specifically tailored to the unique symptoms and the natural course/history of GPP.
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Affiliation(s)
- S E Choon
- Hospital Sultanah Aminah Johor Bahru, Clinical School Johor Bahru, Monash University Malaysia, Johor Bahru, Malaysia
| | | | - P Wolf
- Department of Dermatology, Medical University of Graz, Graz, Austria
| | - R K Jha
- Boehringer Ingelheim International GmBH, Ingelheim am Rhein, Germany
| | - K I Fischer
- Boehringer Ingelheim International GmBH, Ingelheim am Rhein, Germany
| | | | | | - S R Marshall
- Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA
| | - A B Gottlieb
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
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Hackley M, Thampy D, Waseh S, Feldman SR, Blauvelt A, Weinberg JM, Schwartzman S, Liao W, Prussick R, Cohen JM, Hsu S. Increased risk of severe generalized pustular psoriasis due to tuberculosis screening delay for spesolimab initiation. J Am Acad Dermatol 2024; 90:408-410. [PMID: 37821053 DOI: 10.1016/j.jaad.2023.09.078] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 09/24/2023] [Accepted: 09/28/2023] [Indexed: 10/13/2023]
Affiliation(s)
- Madison Hackley
- Department of Dermatology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania
| | - Daphne Thampy
- Department of Dermatology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania
| | - Shayan Waseh
- Department of Dermatology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania
| | - Steven R Feldman
- Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | | | - Jeffrey M Weinberg
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Sergio Schwartzman
- Hospital for Special Surgery, New York Prsebyterian Hospital, Weill Cornell Medical Center, New York, New York
| | - Wilson Liao
- Department of Dermatology, University of California San Francisco, San Francisco, California
| | - Ronald Prussick
- Department of Dermatology, George Washington University, Washington, DC
| | - Jeffrey M Cohen
- Department of Dermatology, Yale School of Medicine, New Haven, Connecticut
| | - Sylvia Hsu
- Department of Dermatology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania.
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47
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Bhutani T, Farberg AS. Clinical and Disease Burden of Patients with Generalized Pustular Psoriasis: A Review of Real-World Evidence. Dermatol Ther (Heidelb) 2024; 14:341-360. [PMID: 38363460 PMCID: PMC10891013 DOI: 10.1007/s13555-024-01103-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 01/17/2024] [Indexed: 02/17/2024] Open
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.
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Affiliation(s)
- Tina Bhutani
- Psoriasis and Skin Treatment Center, University of California at San Francisco, San Francisco, CA, 94118, USA.
| | - Aaron S Farberg
- Bare Dermatology, Dallas, TX, USA
- Baylor Scott and White Health System, Dallas, TX, USA
- University of North Texas Health Science Center, Fort Worth, TX, USA
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48
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Vasudevan B, Das P, Bhatt S. Pustular psoriasis: A distinct aetiopathogenic and clinical entity. Indian J Dermatol Venereol Leprol 2024; 90:19-29. [PMID: 37317717 DOI: 10.25259/ijdvl_542_2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 04/12/2023] [Indexed: 06/16/2023]
Abstract
Pustular psoriasis is a distinct subset of psoriasis that presents with involvement of the skin in the form of sterile pustules along with systemic manifestations. Though it has been conventionally grouped under the umbrella of psoriasis, recent research has shed light on its pathogenetic mechanisms associated with the IL-36 pathway, which is distinct from conventional psoriasis. Pustular psoriasis in itself is a heterogeneous entity consisting of various subtypes, including generalised, localised, acute, and chronic forms. There is confusion regarding its current classification as entities like deficiency of IL-36 antagonist (DITRA) which are closely related to pustular psoriasis both in their pathogenetic mechanism and its clinical manifestations, are not included under pustular psoriasis. Entities like palmoplantar pustulosis, which presents with similar clinical features but is pathogenetically distinct from other forms of pustular psoriasis, are included under this condition. Management of pustular psoriasis depends upon its severity; while some of the localised variants can be managed with topical therapy alone, the generalised variants like Von Zumbusch disease and impetigo herpetiformis may need intensive care unit admission and tailor-made treatment protocols. The advent of newer biologics and better insight into the pathogenesis of pustular psoriasis has opened the way for newer therapies, including tumour necrosis factor-alpha inhibitors, interleukin-1 inhibitors, interleukin-17 inhibitors, and granulocyte monocyte apheresis. It continues to be an enigma whether pustular psoriasis is actually a variant of psoriasis or an entirely different disease entity, though we feel that it is an entirely different disease process.
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Affiliation(s)
- Biju Vasudevan
- Department of Dermatology, Armed Forces Medical College (AFMC), Wanowarie, Pune, India
| | - Pankaj Das
- Department of Dermatology, Armed Forces Medical College (AFMC), Wanowarie, Pune, India
| | - Siddharth Bhatt
- Department of Dermatology, Armed Forces Medical College (AFMC), Wanowarie, Pune, India
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Coscarella G, Falco GM, Palmisano G, Ippoliti E, De Luca E, Gori N, Di Nardo L, Caldarola G, De Simone C, Chiricozzi A, Peris K. Low grade of satisfaction related to the use of current systemic therapies among pustular psoriasis patients: a therapeutic unmet need to be fulfilled. Front Med (Lausanne) 2024; 10:1295973. [PMID: 38274451 PMCID: PMC10808801 DOI: 10.3389/fmed.2023.1295973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 12/18/2023] [Indexed: 01/27/2024] Open
Abstract
Introduction Pustular psoriasis is considered a separate entity from plaque psoriasis and can be categorized as generalized pustular psoriasis (GPP), acrodermatitis continua of Hallopeau, or palmoplantar pustulosis (PPP). Current guidelines mostly include treatment options that have not been specifically developed for the treatment of pustular psoriasis. The majority of them does not have indication for the treatment of pustular psoriasis. Their effectiveness and safeness have been described in small cohort-based studies or case series with a low level of evidence. Previous studies evaluated treatment response through physician-based assessment but none reported patient satisfaction to treatment, quality of life and patient perception of disease severity during systemic therapies, particularly with biologics commonly used in plaque psoriasis. This study aimed to investigate patient satisfaction to treatment and patients' quality of life during treatment, correlating patient-reported outcomes with residual disease severity. Methods A cross-sectional, cohort-based, single center study included patients affected by pustular psoriasis undergoing treatment with systemic agents. Demographic, clinical characteristics were collected. Treatment satisfaction as well as disease severity were assessed through dedicated assessment scores. Results A total of 31 patients affected by GPP or PPP were included. Despite biologic treatment, 80.6% of patients continued to experience mild-to-severe disease activity, with discrepancies between patient and physician assessments. Patients reported a substantial impairment in their quality of life, with notable limitations in physical activity and emotional distress. Mental health conditions, such as depression and anxiety disorders, were common. Treatment satisfaction varied, with moderate scores for effectiveness and convenience. Only a small proportion of patients (41.9%) reported complete or high overall treatment satisfaction. GPP and PPP subcohorts exhibited similar quality of life and treatment satisfaction levels. Discussion This study highlights the suboptimal control of PP despite biologic therapies, resulting in a significant impact on patients' quality of life and treatment satisfaction. The findings highlight the need for specific therapies and standardized guidelines for managing PP. New targeted therapies, such as spesolimab, hold promise for optimizing treatment satisfaction and improving patients' quality of life in this challenging condition. Future research should focus on refining treatment strategies to address the unmet needs of PP patients comprehensively.
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Affiliation(s)
- Giulia Coscarella
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gennaro Marco Falco
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gerardo Palmisano
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Elena Ippoliti
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Eleonora De Luca
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Niccolò Gori
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Lucia Di Nardo
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giacomo Caldarola
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Clara De Simone
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Andrea Chiricozzi
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Ketty Peris
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
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Balato A, Ambrogio F, Burlando M, Carrera CG, Chiricozzi A, Esposito M, Piaserico S, Teoli M, Gisondi P. Commentary: Unmet Needs in Generalized Pustular Psoriasis in Clinical Practice. Dermatol Ther (Heidelb) 2024; 14:5-13. [PMID: 38048034 PMCID: PMC10828309 DOI: 10.1007/s13555-023-01073-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 11/13/2023] [Indexed: 12/05/2023] Open
Affiliation(s)
- Anna Balato
- Dermatology Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Francesca Ambrogio
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Dermatology, University of Bari Aldo Moro, Bari, Italy
| | - Martina Burlando
- Department of Dermatology, Dipartimento di Scienze Della Salute, DISSAL, University of Genoa, 16100, Genoa, Italy
- IRCCS Opsedale Policlinico San Martino, 16100, Genoa, Italy
| | - Carlo Giovanni Carrera
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Andrea Chiricozzi
- UOC of Dermatology, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy
- Dermatology, Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maria Esposito
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
- UOSD General and Oncologic Dermatology, San Salvatore Hospital, L'Aquila, Italy
| | - Stefano Piaserico
- Dermatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | - Miriam Teoli
- San Gallicano Dermatological Institute IRCCS, Rome, Italy
| | - Paolo Gisondi
- Department of Medicine, Section of Dermatology and Venereology, University of Verona, Verona, Italy.
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