Tsen-Fang Tsai’s research while affiliated with Taipei Medical University Hospital and other places

Palmoplantar pustulosis (PPP) is a chronic, relapsing disease with sterile pustules involving the palms and soles. The pathogenesis of PPP remains unclear and there is currently no standard treatment. We present three cases of recalcitrant PPP treated with topical 2% crisaborole cream in our clinic from October 2024 to February 2025. All of the patients had received skin biopsy to prove their diagnosis and had been treated with various treatments with limited response. After 4 weeks of topical crisaborole, their palmoplantar pustulosis area and severity index decreased from 7.2 to 2.8, 9 to 1.8, and 28.4 to 0, respectively. Given that PPP involves the skin locally, an effective topical treatment may provide a convenient, inexpensive alternative for such patients. The positive response of topical crisaborole observed in our cases also echoes the efficacy of apremilast, a systemic phosphodiesterase 4 (PDE4) inhibitor which successfully treated PPP in other reports, highlighting the potential role of PDE4 in the pathophysiology of PPP. Further studies are needed for a more comprehensive evaluation.

Psoriasis, a chronic immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation and inflammatory cell infiltration, involves multiple distinct programmed cell death pathways in its pathogenesis. Following the Nomenclature Committee on Cell Death recommendations, we analyzed the current literature examining diverse modes of cellular death in psoriatic lesions, with particular focus on keratinocyte cell death patterns and their molecular signatures. Analysis revealed several distinct cell death mechanisms: autophagy dysfunction through IL-17A pathways, decreased apoptotic activity in lesional skin, medication targeting anoikis in psoriasis, upregulated necroptosis mediated by RIPK1/MLKL signaling, gasdermin-mediated pyroptosis with enhanced IL-1β secretion, coordinated PANoptotic activation through specialized complexes, PARP1-mediated parthanatos promoting cutaneous inflammation, iron-dependent ferroptosis correlating with Th22/Th17 responses, copper-dependent cuproptosis with elevated MTF1/ATP7B/SLC31A1 expression, and NETosis amplifying immune responses through interaction with the Th17 axis. The intricate interplay between these cell death mechanisms has led to the development of targeted therapeutic strategies, including mTOR inhibitors for autophagy modulation, RIPK1 inhibitors for necroptosis, and various approaches targeting ferroptosis and NETosis, providing new directions for more effective psoriasis treatments.

Psoriasis, a chronic immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation and inflammatory cell infiltration, involves multiple distinct programmed cell death pathways in its pathogenesis. Following the Nomenclature Committee on Cell Death recommendations, we analyzed current literature examining diverse modes of cellular death in psoriatic lesions, with particular focus on keratinocyte cell death patterns and their molecular signatures. Analysis revealed several distinct cell death mechanisms: autophagy dysfunction through IL-17A pathways, decreased apoptotic activity in lesional skin, medication targeting anoikis in psoriasis, upregulated necroptosis mediated by RIPK1/MLKL signaling, gasdermin-mediated pyroptosis with enhanced IL-1β secretion, coordinated PANoptotic activation through specialized complexes, PARP1-mediated parthanatos promoting cutaneous inflammation, iron-dependent ferroptosis correlating with Th22/Th17 responses, copper-dependent cuproptosis with elevated MTF1/ATP7B/SLC31A1 expression, and NETosis amplifying immune responses through interaction with the Th17 axis. The intricate interplay between these cell death mechanisms has led to the development of targeted therapeutic strategies, including mTOR inhibitors for autophagy modulation, RIPK1 inhibitors for necroptosis, and various approaches targeting ferroptosis and NETosis, providing new directions for more effective psoriasis treatments.

Ethnic differences of the clinicopathological characteristics in many immune-mediated skin diseases have been reported, including psoriasis vulgaris (PV). However, the ethnic differences of pustular psoriasis have been less studied. The aim of this study was to compare the differences in epidemiology, genetic background, clinical manifestations, treatment patterns and responses among Asian and non-Asian patients with pustular psoriasis, including generalized pustular psoriasis (GPP) and acrodermatitis continua of Hallopeau (ACH). This systematic review was based on a comprehensive search of Cochrane, PubMed, and Embase databases from earliest available date to 31 December 2024, and all studies reporting on patients with either GPP or ACH irrespective of study design. Studies with study size below five patients or those focusing on quality of life or economic aspects were excluded. In each publication, the ethnic composition, demographics information, disease course and manifestation, as well as genetic mutations, treatment type and response were collected if available. Of 2187 screened studies, 141 studies were included, with the majority being cohort studies. Compared with other ethnicities, East Asians with GPP carried more null IL36RN mutations, while AP1S3 mutations seemed absent in Asians. Phenotypically, Asians had younger onset age, bimodal age distribution, less family history of PV, and more scalp/nail involvement. In Asians, absence of coexisting PV was associated with severe disease. GPP with PV had shorter pre-pustular duration among Asians than non-Asians. Use of acitretin appeared higher and more effective among East Asians compared with other populations. In ACH, Asians mostly carried homozygous null IL36RN mutations and had younger onset age, more multi-digit involvement, persistent treatment course, and more coexisting GPP than Europeans. Biologics use was less common in Asia in both GPP and ACH than in Europe and the US. This systematic review underscores notable ethnic differences in genetic profiles, clinical features, and therapeutic responses in GPP and ACH. The diagnosis of GPP and ACH may differ across studies and the true impacts of ethnicities on these differences remain to be confirmed. Nonetheless, the results from this study enhance our understanding of the heterogeneous characteristics of GPP and ACH, highlighting the necessity of incorporating ethnic differences into the diagnosis, genetic testing, and management strategies for patients with GPP and ACH.

Erythrodermic psoriasis (EP) is a severe and challenging variant of psoriasis that often shows poor drug survival. While risankizumab, an IL‐23 inhibitor, has demonstrated efficacy in patients with moderate‐to‐severe plaque psoriasis, its effectiveness in patients with a history of EP is less explored. This study aimed to evaluate treatment response to risankizumab and identify potential predictors influencing the treatment response. In this single‐center, longitudinal retrospective study, we included 56 patients treated with risankizumab between August 1, 2016, and June 1, 2023, of whom 22 had a history of EP. Treatment response was assessed using the Psoriasis Area and Severity Index (PASI), and the impact of patient characteristics, including prior biologic exposure and HLA‐Cw genotypes, on treatment response was analysed using the Mann–Whitney U test. Throughout the 100‐week follow‐up, patients with a history of EP exhibited a poorer treatment response compared to those without such a history. Among patients with a history of EP, those with prior exposure to guselkumab and those treated with more than five biologics demonstrated a decreased response to risankizumab. Additionally, there was a non‐significant trend indicating that HLA‐Cw1–negative patients responded better to risankizumab. This case series indicated that risankizumab might be an effective and sustainable treatment option for most patients with a history of EP. However, prior exposure to multiple biologics, particularly those with a similar mode of action targeting IL‐23, may reduce its effectiveness. The potential association between HLA‐Cw1 genotype and treatment response warrants further investigation.

Prof. Morita presents the EFFISAYIL® 2 clinical trial, which investigated spesolimab treatment for the prevention of GPP flares.

Risankizumab (Skyrizi®, Abbvie, North Chicago, IL, USA) is a humanized immunoglobulin (Ig) G1 monoclonal antibody targeting the p19 subunit of IL-23, thereby inhibiting IL-23-dependent releasing of proinflammatory cytokines in plaque psoriasis. Risankizumab is licensed is most countries for the treatment of patients with moderate-to-severe plaque psoriasis, and in Japan for generalized pustular psoriasis, erythrodermic psoriasis and palmoplantar pustulosis. Risankizumab showed higher efficacy and favorable safety profiles in patients with moderate-to-severe plaque psoriasis, compared with adalimumab, secukinumab and ustekinumab in several randomized controlled phase 3 pivotal studies and among real-life data in large retrospective studies. Furthermore, its high efficacy even in patients with prior biologic failure, better drug survival, less need for biologic switch and longer drug-free remission durations have also been shown in real-life settings and in long-term follow-up. In addition, reports of both reduced dosing and increased (bolus) dosing exist which increase our ability to use risankizumab more flexibly in an era of personalized medicine. Also, the use of risankizumab in several special population, such as elderly, Asian people, erythrodermic psoriasis, patients with high induction doses, pregnancy and human immunodeficiency virus group are discussed.

Background Generalised pustular psoriasis (GPP) is a chronic, systemic, neutrophilic inflammatory disease. A previous Delphi panel established areas of consensus on GPP, although patient perspectives were not included, and aspects of treatment goals remain unclear. Objectives To identify and achieve consensus on refined, specific treatment goals for GPP treatment via a Delphi panel with patient participation. Methods Statements were generated based on a systematic literature review and revised by a Steering Committee. Statements were categorised into overarching principles, short-term treatment goals and long-term treatment goals. A global panel of 30 dermatologists and three patient representatives voted in agreement or disagreement with each statement. Consensus was defined as ≥80% approval by panellists. Results Consensus was reached in the first round of voting and ≥90% agreement was reached for 23/26 statements. In summary, GPP requires a timely, tailored treatment plan, co-developed by patients and physicians, that involves a multidisciplinary approach and addresses the complexity, heterogeneity and chronicity of the disease. Short-term treatment goals should include pustule clearance within 7 days and prevention of pustule recurrence, reduction of cutaneous symptom burden (≥ −4 points on the Itch and Skin Pain Numeric Rating Scale), improvement in systemic symptoms (e.g. resolution of fever within 3 days of treatment initiation and reduced fatigue), prevention of life-threatening complications, and progressive improvement of inflammatory biomarkers. In patients with comorbid psoriatic diseases, treatment decisions should prioritise GPP. Long-term treatment goals should include minimising disease activity through flare prevention and symptom control between flares, sustained disease control, management of comorbidities and improvement in quality of life (QoL). Small differences in perception between patients and physicians regarding the importance of certain treatment goals, e.g. avoiding hair and/or nail loss to improve QoL, reflect the complexity of assessing treatment goals and emphasise the need for a patient-centred approach. Conclusions In the first global Delphi panel in GPP to include patient perspectives, consensus between dermatologists and patients was achieved on overarching principles of treatment, short-term and long-term treatment goals for GPP. These findings provide valuable insights for developing guidelines that consider the perspectives of both patients and physicians in the treatment of GPP.