To the Editor: Generalized pustular psoriasis (GPP) is a rare, severe inflammatory skin disease characterized by widespread sterile pustules and systemic inflammation, often requiring urgent medical intervention.1 Although targeted therapies have improved disease control,2 the long-term clinical trajectory of GPP remains incompletely understood, and predictors of disease recurrence have not been clearly established.1,3
To characterize disease course heterogeneity and identify predictors of recurrence, we conducted a retrospective case series of 40 adult patients with GPP treated at Jichi Medical University Hospital between 2006 and 2024. Diagnosis was based on clinical and histopathologic findings, and all cases fulfilled the International Psoriasis Council diagnostic criteria with exclusion of other pustular dermatoses.4 Eight cases were initially misdiagnosed as drug eruptions, including acute generalized exanthematous pustulosis, and 2 as erythema multiforme.
The cohort included 21 women and 19 men with a median follow-up of 5.7 years (range, 0.3-44.8 years). Among the 17 patients who underwent genetic testing, pathogenic variants were identified in IL36RN (n = 3) and MEFV (n = 1). Twenty-four patients (60%) experienced a single flare, whereas 16 patients (40%) experienced multiple flares (Table I, Supplementary Table I, available via Mendeley at https://data.mendeley.com/datasets/9rtdkv4z3s/1). Among patients with recurrent disease, flare intervals varied widely from 0.17 to 17 years (median, 3.2 years), demonstrating substantial unpredictability. Some patients remained flare-free for over a decade, whereas others relapsed within months. Among patients with preceding psoriasis vulgaris or palmoplantar pustulosis, the interval to onset of GPP also showed substantial variability (Supplementary Table II, available via Mendeley at https://data.mendeley.com/datasets/9rtdkv4z3s/1).
Table I.
Baseline characteristics and clinical course summary of patients with generalized pustular psoriasis (N = 40)
| Characteristic | Value |
|---|---|
| Age at onset, mean ± SD, y | 54.6 ± 22.4 |
| Female sex, n (%) | 21 (52.5) |
| Follow-up duration, median [range], y | 5.7 [0.3-44.8] |
| Psoriatic arthritis, n (%) | 10 (25.0) |
| Preceding plaque psoriasis, n (%) | 26 (65.0) |
| IL36RN pathogenic variants, n (%) | 3/17 (17.6) |
| Number of flares during follow-up, n (%) | Single flare 24 (60.0) Multiple flares 16 (40.0) |
| Required systemic therapy, n (%) | 35 (87.5) |
| Managed with rest and topical therapy alone, n (%) | 5 (12.5) |
Importantly, univariate analyses using Fisher’s exact test and Mann–Whitney U test did not identify any significant baseline predictors of multiple flares. Sex, body mass index, psoriatic arthritis, fever at presentation, identifiable flare triggers, and prior psoriasis vulgaris were not associated with recurrence risk. These findings indicate that disease course cannot be reliably predicted at initial presentation, and even patients with apparently stable disease remain at risk of future exacerbations, consistent with prior case series demonstrating recurrent flares and the need for ongoing medical management.5
Treatment patterns further reflected disease heterogeneity. Thirty-five patients (87.5%) required systemic therapy, with the number of systemic agents ranging from 1 to 8, whereas 12.5% were managed with rest and topical therapy alone without systemic treatment during follow-up. Treatment regimens included oral retinoids, systemic corticosteroids, cyclosporine, and multiple biologic agents targeting distinct inflammatory pathways. Treatment histories are summarized in Supplementary Table III, available via Mendeley at https://data.mendeley.com/datasets/9rtdkv4z3s/1. Treatment sequences varied considerably between patients, without a consistent therapeutic progression, reflecting individualized treatment decisions based on clinical response and severity (Fig 1).
Fig 1.
Treatment pathway for 40 patients with generalized pustular psoriasis. A Sankey diagram illustrating transitions among first-, second-, and third-line therapies in individual patients. The width of each flow is proportional to the number of patients receiving each treatment.
Identifiable triggers were present in 44.8% (26 of 58) of flares, including medications, pregnancy, infection, and treatment tapering or discontinuation. However, recurrence associated with the same trigger was observed in only one case, which occurred during pregnancy, indicating limited predictive value of prior trigger exposure. Detailed trigger information is provided in Supplementary Table IV, available via Mendeley at https://data.mendeley.com/datasets/9rtdkv4z3s/1.
This case series demonstrates that GPP exhibits highly variable flare intervals and treatment courses, without reliable baseline predictors of recurrence. Even patients with prolonged remission may experience sudden flares. These findings support individualized long-term monitoring and flexible therapeutic strategies.
Conflicts of interest
Dr Kishimoto received honoraria from Amgen K.K.; Boehringer Ingelheim Japan, Inc; Bristol-Myers Squibb K.K.; Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K.; Maruho Co, Ltd; Novartis Pharma K.K.; Sun Pharmaceutical Industries Ltd; Taiho Pharmaceutical Co, Ltd; and UCB Japan Co, Ltd. Dr Ohtsuki received speaker fees from Amgen K.K., Sanofi K.K., Maruho Co, Ltd, Eli Lilly Japan K.K., and UCB Japan Co, Ltd; consultancy or advisory fees from AbbVie GK, Nippon Boehringer Ingelheim Co, Ltd, and Bristol-Myers Squibb K.K.; and scholarship donations to his department from AbbVie GK, Taiho Pharmaceutical Co, Ltd, Maruho Co, Ltd, Torii Pharmaceutical Co, Ltd, Eisai Co, Ltd, and Sun Pharma Japan Ltd. Dr Komine received research grants from Nippon Boehringer Ingelheim Co, Ltd. and Eli Lilly Japan K.K.; speaker fees from Nippon Boehringer Ingelheim Co, Ltd, UCB Japan Co, Ltd, AbbVie GK, Sun Pharma Japan Ltd, Janssen Pharmaceutical K.K., Bristol-Myers Squibb K.K., and Maruho Co, Ltd; and scholarship donations to the Department of Dermatology from Sun Pharma Japan Ltd, Maruho Co, Ltd, the Japan Organization of Clinical Dermatologists, Taiho Pharmaceutical Co, Ltd, AbbVie GK, Eisai Co, Ltd, and Torii Pharmaceutical Co, Ltd. Dr Kamiya has no conflict of interest to declare.
Footnotes
Funding sources: None.
Patient consent: Not applicable.
IRB approval status: This study was reviewed and approved by the Ethical Committee of Jichi Medical University (approval #23-073).
References
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