RARE DISEASE
Generalized pustular psoriasis
Generalized pustular psoriasis
Generalized pustular psoriasis
Synonyms: GPP
Synonyms: GPP
Synonyms: GPP
Drug discovery
3
drugs
With orphan designations
Overview
Generalized pustular psoriasis (GPP) is a rare, life-threatening neutrophilic skin disease marked by sudden widespread sterile pustules, erythema, and systemic inflammation (fever, malaise) [1][3][6][11]. It arises from dysregulated IL-36 signaling and environmental triggers (e.g., steroid withdrawal, infections) [6][11][18]. Distinct from plaque psoriasis, GPP requires urgent treatment to prevent sepsis, organ failure, or death [1][3][11].
Categories: rare genetic diseases, rare skin diseases
Research Papers
731 drug discovery papers about Generalized pustular psoriasis, with 2 first-in-class and 9 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
731 drug discovery papers about Generalized pustular psoriasis, with 2 first-in-class and 9 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-10 | Efficacy and safety of Janus kinase and TYK2 inhibitors in the treatment of generalized pustular psoriasis and palmoplantar pustulosis: a systematic review.
Pustular psoriasis (PP), including generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP), is a rare and severe inflammatory dermatosis distinct from plaque psoriasis and associated with significant unmet therapeutic needs. Although advances in immunopathogenesis have identified key cytokine and signaling pathways, evidence-based treatment options remain limited. This systematic review evaluates the efficacy and safety of emerging Janus kinase (JAK) and tyrosine kinase (TYK) inhibitors in the management of PP. This systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/Medline, Ovid-Embase, and Web of Science were searched from inception to November 15th, 2025, to identify all English-language clinical studies evaluating JAK or TYK inhibitors in patients with GPP or PPP. Methodological quality and risk of bias were independently assessed using National Institutes of Health quality assessment tools and the Murad et al. criteria. Of 2,259 records identified, 33 clinical studies (177 patients with GPP or PPP) met the predefined eligibility criteria. TYK inhibitors were evaluated in three studies of deucravacitinib (n = 11), which showed variable efficacy across reports: improvements in PASI/PPPASI, symptoms, and quality of life in some patients, and discontinuation due to insufficient response in others, with no serious adverse events reported. JAK inhibitors were evaluated in 30 studies involving 166 patients and were associated with improvements in disease severity, quality of life, and physician-assessed outcomes. Favorable responses were reported in observational studies, while rapid clinical improvement was frequently described in case-based evidence. Overall, treatment was generally well tolerated, although interpretation is limited by the predominance of uncontrolled studies and heterogeneous data. Available evidence indicates that JAK and TYK inhibitors may provide clinical benefit in GPP and PPP, particularly in refractory cases, with generally acceptable safety profiles. However, conclusions are limited by small, heterogeneous studies, and well-designed randomized controlled trials with longer follow-up are needed to establish long-term efficacy and safety.
2026-08-06 | Safety and Efficacy of Deucravacitinib in Japanese Patients With Moderate to Severe Plaque Psoriasis: 5-Year Analysis of the Phase 3 POETYK PSO-1, PSO-4, and Long-Term Extension Trials.
Deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, is approved in multiple countries for the treatment of moderate to severe plaque psoriasis, as well as generalized pustular and erythrodermic psoriasis in Japan. Deucravacitinib 6 mg once daily was efficacious and well tolerated through 3 years in the pooled population of Japanese patients in the POETYK PSO-1 and PSO-4 trials who entered the ongoing open-label POETYK long-term extension trial. Safety and efficacy of deucravacitinib were evaluated through 5 years (256 weeks; data cutoff September 2, 2024) in Japanese patients who received continuous deucravacitinib in PSO-1 or PSO-4 or who crossed over from placebo to deucravacitinib at Week 16 in PSO-1. Safety was evaluated via adverse event (AE) exposure-adjusted incidence rates (EAIRs); efficacy was evaluated via endpoints including ≥ 75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) and static Physician Global Assessment (sPGA) score of 0/1 (clear/almost clear). At data cutoff, 136 patients had received at least one deucravacitinib dose; 77.2% had > 48 months and 39.7% had > 60 months of total deucravacitinib exposure. EAIRs per 100 person-years were 182.1 (any AEs), 6.9 (serious AEs), 3.0 (discontinuations due to AEs), 1.6 (serious infections), 1.6 (herpes zoster events), 0.5 (major adverse cardiovascular events), and 1.4 (malignancies). Clinical responses (as observed) were maintained over 5 years in PSO-1 patients receiving continuous deucravacitinib treatment from baseline (PASI 75: Year 1, 88.9%; Year 5, 85.7%; sPGA 0/1: Year 1, 74.1%; Year 5, 71.4%); results were consistent regardless of imputation method (modified nonresponder imputation, treatment failure rule). Year 1 response rates were also maintained through Year 5 in PSO-4 patients and in PSO-1 patients who crossed over from placebo. These findings support the long-term safety and durable efficacy profile of deucravacitinib through 5 years in Japanese patients with psoriasis.
2026-08-05 | INDIVIDUAL ARTICLE: Generalized Pustular Psoriasis: A Contemporary Review of Diagnosis, Pathophysiology, and IL-36 Pathway-Directed Management.
Emerging epidemiologic, clinical, and real-world data establish GPP as a distinct disease entity associated with high rates of hospitalization, multisystem involvement, and increased mortality. Accurate diagnosis requires recognition of characteristic cutaneous findings together with laboratory and clinical evidence of systemic involvement, and exclusion of key mimickers such as acute generalized exanthematous pustulosis, as well as recognition of patient-reported systemic symptoms such as fever, malaise, and joint pain. Advances in pathophysiologic understanding have identified dysregulated innate immune signaling centered on the interleukin-36 (IL-36) pathway as the primary driver of neutrophilic inflammation and pustule formation. Randomized clinical trials, real-world evidence, and meta-analyses consistently demonstrate that IL-36 receptor blockade achieves rapid and reliable control of acute GPP flares and provides a rational strategy for flare prevention. In contrast, off-label biologic therapies targeting IL-17, IL-23, or tumor necrosis factor-α show more variable and often delayed efficacy, particularly for acute disease control. Contemporary evidence supports a paradigm shift toward disease-specific, pathway-directed management of GPP, with IL-36 pathway inhibition positioned as the cornerstone of modern therapy. .
2026-08-01 | Effectiveness and Safety of Spesolimab in Adolescents and Adults with Generalized Pustular Psoriasis
Purpose: Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory skin disease characterized by widespread erythema, pustules and systemic involvement. Evidence-based treatment guidelines for adolescents with GPP remain limited. Spesolimab, a parenteral humanized monoclonal antibody targeting the interleukin-36 receptor, has emerged as a novel therapeutic option; however, data on its use in adolescents are scarce. Here, we aimed to evaluate the effectiveness of spesolimab in treating GPP episodes in adolescents and compared their outcomes with those in adults. Patients and Methods: We analyzed the management of GPP episodes with spesolimab in two adolescent and four adult patients in our unit and conducted a literature review involving 25 patients. Clinical outcomes included response to treatment, pustule resolution, and infection management. Spesolimab achieved rapid and sustained symptom control in all patients, including those with coexisting plaque psoriasis. Results: Twenty-two patients (71.0%) experienced complete pustule resolution within 1 week, and all 31 patients achieved complete pustule resolution by week 4. Treatment responses in adolescents were comparable to those in adults. Infections were identified as key exacerbating factors and managed accordingly. Conclusion: IL-36R inhibitors, such as spesolimab, are potentially effective and safe treatment for both adolescent and adult patients with GPP. Future studies should explore the long-term efficacy of spesolimab and its application strategy of sustained disease control. Keywords: spesolimab, IL-36 receptor antagonist, pustular psoriasis, drug therapy
2026-07-30 | Combination of Low-Dose Methotrexate and Cyclosporine in a Patient with Generalized Pustular Psoriasis: A Case Report
Generalized pustular psoriasis (GPP) is a rare and life-threatening chronic inflammatory skin disease characterized by sterile pustules and systemic inflammation, associated with substantial disease burden due to frequent flares. Limited guidelines and suboptimal treatment outcomes have led to various therapeutic approaches, including combination therapy. This case report aims to describe the use of low-dose methotrexate and cyclosporine combination in a GPP patient and evaluate the clinical response achieved. A 40-year-old woman presented with painful pustules distributed throughout the entire body accompanied by a burning sensation. She had undergone methotrexate therapy for 1 year before self-cessation due to insignificant improvement. Dermatological examination revealed generalized multiple pustules on an erythematous base, some confluent and covered by scales. Histopathological examination showed abundant neutrophils in the superficial epidermal layer along with focal neutrophils and mild spongiosis, supporting the diagnosis of GPP. The patient was given methotrexate 7.5 mg weekly and cyclosporine 100 mg daily for 5 weeks, showing significant clinical improvement, then maintained with methotrexate 7.5 mg weekly monotherapy. Combination therapy for GPP, particularly methotrexate and cyclosporine, has demonstrated faster and better clinical responses compared to monotherapy, with response rates of 70–90%. Cyclosporine provides rapid disease control, while methotrexate offers sustained immunomodulation. Both agents carry risks of adverse effects, necessitating careful dose selection and close monitoring. This case report demonstrates that low-dose methotrexate and cyclosporine combination is effective in managing refractory GPP with significant clinical improvement after 5 weeks of therapy, making it a promising therapeutic option for severe and refractory GPP cases.
2026-08-10 | Efficacy and safety of Janus kinase and TYK2 inhibitors in the treatment of generalized pustular psoriasis and palmoplantar pustulosis: a systematic review.
Pustular psoriasis (PP), including generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP), is a rare and severe inflammatory dermatosis distinct from plaque psoriasis and associated with significant unmet therapeutic needs. Although advances in immunopathogenesis have identified key cytokine and signaling pathways, evidence-based treatment options remain limited. This systematic review evaluates the efficacy and safety of emerging Janus kinase (JAK) and tyrosine kinase (TYK) inhibitors in the management of PP. This systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/Medline, Ovid-Embase, and Web of Science were searched from inception to November 15th, 2025, to identify all English-language clinical studies evaluating JAK or TYK inhibitors in patients with GPP or PPP. Methodological quality and risk of bias were independently assessed using National Institutes of Health quality assessment tools and the Murad et al. criteria. Of 2,259 records identified, 33 clinical studies (177 patients with GPP or PPP) met the predefined eligibility criteria. TYK inhibitors were evaluated in three studies of deucravacitinib (n = 11), which showed variable efficacy across reports: improvements in PASI/PPPASI, symptoms, and quality of life in some patients, and discontinuation due to insufficient response in others, with no serious adverse events reported. JAK inhibitors were evaluated in 30 studies involving 166 patients and were associated with improvements in disease severity, quality of life, and physician-assessed outcomes. Favorable responses were reported in observational studies, while rapid clinical improvement was frequently described in case-based evidence. Overall, treatment was generally well tolerated, although interpretation is limited by the predominance of uncontrolled studies and heterogeneous data. Available evidence indicates that JAK and TYK inhibitors may provide clinical benefit in GPP and PPP, particularly in refractory cases, with generally acceptable safety profiles. However, conclusions are limited by small, heterogeneous studies, and well-designed randomized controlled trials with longer follow-up are needed to establish long-term efficacy and safety.
2026-08-06 | Safety and Efficacy of Deucravacitinib in Japanese Patients With Moderate to Severe Plaque Psoriasis: 5-Year Analysis of the Phase 3 POETYK PSO-1, PSO-4, and Long-Term Extension Trials.
Deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, is approved in multiple countries for the treatment of moderate to severe plaque psoriasis, as well as generalized pustular and erythrodermic psoriasis in Japan. Deucravacitinib 6 mg once daily was efficacious and well tolerated through 3 years in the pooled population of Japanese patients in the POETYK PSO-1 and PSO-4 trials who entered the ongoing open-label POETYK long-term extension trial. Safety and efficacy of deucravacitinib were evaluated through 5 years (256 weeks; data cutoff September 2, 2024) in Japanese patients who received continuous deucravacitinib in PSO-1 or PSO-4 or who crossed over from placebo to deucravacitinib at Week 16 in PSO-1. Safety was evaluated via adverse event (AE) exposure-adjusted incidence rates (EAIRs); efficacy was evaluated via endpoints including ≥ 75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) and static Physician Global Assessment (sPGA) score of 0/1 (clear/almost clear). At data cutoff, 136 patients had received at least one deucravacitinib dose; 77.2% had > 48 months and 39.7% had > 60 months of total deucravacitinib exposure. EAIRs per 100 person-years were 182.1 (any AEs), 6.9 (serious AEs), 3.0 (discontinuations due to AEs), 1.6 (serious infections), 1.6 (herpes zoster events), 0.5 (major adverse cardiovascular events), and 1.4 (malignancies). Clinical responses (as observed) were maintained over 5 years in PSO-1 patients receiving continuous deucravacitinib treatment from baseline (PASI 75: Year 1, 88.9%; Year 5, 85.7%; sPGA 0/1: Year 1, 74.1%; Year 5, 71.4%); results were consistent regardless of imputation method (modified nonresponder imputation, treatment failure rule). Year 1 response rates were also maintained through Year 5 in PSO-4 patients and in PSO-1 patients who crossed over from placebo. These findings support the long-term safety and durable efficacy profile of deucravacitinib through 5 years in Japanese patients with psoriasis.
2026-08-05 | INDIVIDUAL ARTICLE: Generalized Pustular Psoriasis: A Contemporary Review of Diagnosis, Pathophysiology, and IL-36 Pathway-Directed Management.
Emerging epidemiologic, clinical, and real-world data establish GPP as a distinct disease entity associated with high rates of hospitalization, multisystem involvement, and increased mortality. Accurate diagnosis requires recognition of characteristic cutaneous findings together with laboratory and clinical evidence of systemic involvement, and exclusion of key mimickers such as acute generalized exanthematous pustulosis, as well as recognition of patient-reported systemic symptoms such as fever, malaise, and joint pain. Advances in pathophysiologic understanding have identified dysregulated innate immune signaling centered on the interleukin-36 (IL-36) pathway as the primary driver of neutrophilic inflammation and pustule formation. Randomized clinical trials, real-world evidence, and meta-analyses consistently demonstrate that IL-36 receptor blockade achieves rapid and reliable control of acute GPP flares and provides a rational strategy for flare prevention. In contrast, off-label biologic therapies targeting IL-17, IL-23, or tumor necrosis factor-α show more variable and often delayed efficacy, particularly for acute disease control. Contemporary evidence supports a paradigm shift toward disease-specific, pathway-directed management of GPP, with IL-36 pathway inhibition positioned as the cornerstone of modern therapy. .
2026-08-01 | Effectiveness and Safety of Spesolimab in Adolescents and Adults with Generalized Pustular Psoriasis
Purpose: Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory skin disease characterized by widespread erythema, pustules and systemic involvement. Evidence-based treatment guidelines for adolescents with GPP remain limited. Spesolimab, a parenteral humanized monoclonal antibody targeting the interleukin-36 receptor, has emerged as a novel therapeutic option; however, data on its use in adolescents are scarce. Here, we aimed to evaluate the effectiveness of spesolimab in treating GPP episodes in adolescents and compared their outcomes with those in adults. Patients and Methods: We analyzed the management of GPP episodes with spesolimab in two adolescent and four adult patients in our unit and conducted a literature review involving 25 patients. Clinical outcomes included response to treatment, pustule resolution, and infection management. Spesolimab achieved rapid and sustained symptom control in all patients, including those with coexisting plaque psoriasis. Results: Twenty-two patients (71.0%) experienced complete pustule resolution within 1 week, and all 31 patients achieved complete pustule resolution by week 4. Treatment responses in adolescents were comparable to those in adults. Infections were identified as key exacerbating factors and managed accordingly. Conclusion: IL-36R inhibitors, such as spesolimab, are potentially effective and safe treatment for both adolescent and adult patients with GPP. Future studies should explore the long-term efficacy of spesolimab and its application strategy of sustained disease control. Keywords: spesolimab, IL-36 receptor antagonist, pustular psoriasis, drug therapy
2026-07-30 | Combination of Low-Dose Methotrexate and Cyclosporine in a Patient with Generalized Pustular Psoriasis: A Case Report
Generalized pustular psoriasis (GPP) is a rare and life-threatening chronic inflammatory skin disease characterized by sterile pustules and systemic inflammation, associated with substantial disease burden due to frequent flares. Limited guidelines and suboptimal treatment outcomes have led to various therapeutic approaches, including combination therapy. This case report aims to describe the use of low-dose methotrexate and cyclosporine combination in a GPP patient and evaluate the clinical response achieved. A 40-year-old woman presented with painful pustules distributed throughout the entire body accompanied by a burning sensation. She had undergone methotrexate therapy for 1 year before self-cessation due to insignificant improvement. Dermatological examination revealed generalized multiple pustules on an erythematous base, some confluent and covered by scales. Histopathological examination showed abundant neutrophils in the superficial epidermal layer along with focal neutrophils and mild spongiosis, supporting the diagnosis of GPP. The patient was given methotrexate 7.5 mg weekly and cyclosporine 100 mg daily for 5 weeks, showing significant clinical improvement, then maintained with methotrexate 7.5 mg weekly monotherapy. Combination therapy for GPP, particularly methotrexate and cyclosporine, has demonstrated faster and better clinical responses compared to monotherapy, with response rates of 70–90%. Cyclosporine provides rapid disease control, while methotrexate offers sustained immunomodulation. Both agents carry risks of adverse effects, necessitating careful dose selection and close monitoring. This case report demonstrates that low-dose methotrexate and cyclosporine combination is effective in managing refractory GPP with significant clinical improvement after 5 weeks of therapy, making it a promising therapeutic option for severe and refractory GPP cases.
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Drug Discovery Landscape
3 orphan drug designations for Generalized pustular psoriasis, including 1 approved therapy.
3 orphan drug designations for Generalized pustular psoriasis, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Recombinant Humanized Anti-interleukin 36R Monoclonal Antibody Injection (HB0034) | antibodies | FDA | 2023-10-16 | — | Shanghai Huaota Biopharmaceutical Co., Ltd. |
imsidolimab | antibodies | FDA | 2020-07-07 | — | Vanda Pharmaceuticals Inc. |
spesolimab-sbzo [Spevigo] | antibodies | FDA | 2018-10-03 | 2022-09-01 | LEO Pharma Inc. |
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