International Consensus Definition and Diagnostic Criteria for Generalized Pustular Psoriasis From the International Psoriasis Council.

Importance: Generalized pustular psoriasis (GPP) lacks internationally accepted definitions and diagnostic criteria, impeding timely diagnosis and treatment and hindering cross-regional clinical and epidemiological study comparisons. Objective: To develop an international consensus definition and diagnostic criteria for GPP using the modified Delphi method. Evidence Review: The rarity of GPP presents a challenge in acquiring comprehensive published clinical data necessary for developing standardized definition and criteria. Instead of relying on a literature search, 43 statements that comprehensively addressed the fundamental aspects of the definitions and diagnostic criteria for GPP were formulated based on expert reviews of 64 challenging GPP cases. These statements were presented to a panel of 33 global GPP experts for voting, discussion, and refinements in 2 virtual consensus meetings. Consensus during voting was defined as at least 80% agreement; the definition and diagnostic criteria were accepted by all panelists after voting and in-depth discussion. Findings: In the first and second modified Delphi round, 30 (91%) and 25 (76%) experts participated. In the initial Delphi round, consensus was achieved for 53% of the statements, leading to the approval of 23 statements that were utilized to develop the proposed definitions and diagnostic criteria for GPP. During the second Delphi round, the final definition established was, "Generalized Pustular Psoriasis is a systemic inflammatory disease characterized by cutaneous erythema and macroscopically visible sterile pustules." It can occur with or without systemic symptoms, other psoriasis types, and laboratory abnormalities. GPP may manifest as an acute form with widespread pustules or a subacute variant with an annular phenotype. The identified essential criterion was, "Macroscopically visible sterile pustules on erythematous base and not restricted to the acral region or within psoriatic plaques." Conclusions and Relevance: The achievement of international consensus on the definition and diagnostic criteria for GPP underscores the importance of collaboration, innovative methodology, and expert engagement to address rare diseases. Although further validation is needed, these criteria can serve as a reference point for clinicians, researchers, and patients, which may contribute to more accurate diagnosis and improved management of GPP.

Effectiveness of systemic treatments on pruritus associated with atopic dermatitis: A systematic review in pediatric patients.

BACKGROUND/OBJECTIVES: Itch is one of the hallmarks of atopic dermatitis (AD), which has a significant impact on the quality of life of pediatric patients with AD and their caregivers. We aimed to conduct a systematic review and meta-analysis to evaluate the antipruritic effects of systemic AD treatments in pediatric patients with AD. METHODS: PubMed, EMBASE, Cochrane, and Web of Science databases were searched, including studies providing original data on the effects of systemic treatment on pruritus in pediatric patients (<18 years) with AD. Placebo-controlled trials reporting a Peak Pruritus Numerical Rating Scale 4 (PP-NRS4) response were included in a meta-analysis. RESULTS: A total of 30 studies were included, with most evidence available for dupilumab. Overall, marked improvements of pruritus (50% or greater reduction in pruritus outcome measurements) were found for treatment with cyclosporin A (2-16 years), dupilumab (6 months-17 years), abrocitinib, and upadacitinib (both 12 and 17 years). Nemolizumab (12-17 years) may be promising in reducing pruritus in pediatric patients; however, data are limited. Only five randomized controlled trials could be included in our meta-analysis, in which dupilumab, abrocitinib, and upadacitinib showed a significantly higher probability of achieving a PP-NRS4 response compared with placebo. Our study was limited by a lack of homogeneity of included studies. CONCLUSIONS: Cyclosporin A, dupilumab, abrocitinib, and upadacitinib are all effective in decreasing pruritus and, therefore, in improving the quality of life in children with AD. As more systemic treatments for AD become available, it will be imperative to incorporate patient-oriented treatment goals such as reduction of pruritus into therapeutic decision-making.

Understanding potential participation barriers to improve trial design and outcomes: clinical trial simulation in palmoplantar pustulosis as a case study.

OBJECTIVES: Evaluate the experiences and perceptions of patients participating in a simulated clinical trial and identify ways to enhance future patient-centric trial designs. DESIGN: International, multicentre, non-interventional, virtual clinical trial visits with patient debriefs and advisory boards. SETTING: Virtual clinic visits and accompanying advisory boards. PARTICIPANTS: Nine patients with palmoplantar pustulosis for simulated trial visits; 14 patients and patient representatives for advisory boards. MAIN OUTCOME MEASURES: Qualitative responses to trial documentation, visit schedule and logistics, and trial design were collected during patient debriefs. Results were discussed at two virtual advisory board meetings. RESULTS: Patients identified key barriers to participation and potential difficulties encountered when attending trial visits and completing assessments. They also proposed recommendations to overcome these challenges. Patients recognised the need for comprehensive informed consent forms, but recommended use of non-technical language, brevity and additional support to aid understanding. Other trial documentations should be relevant to the disease and include known efficacy and safety of the study drug. Patients were concerned about receiving placebo, stopping existing medications and being unable to receive the study drug after trial completion; therefore, patients and physicians recommended an open-label extension following trial completion. Trial visits were too numerous (n=20) and too long (3-4 hours each); patients recommended improvements to the design to make best use of their time and reduce unnecessary waiting. They also requested financial and logistical support. Patients expressed a desire for study outcomes that matter to them, related to their ability to undertake normal daily activities and not be a burden to others. CONCLUSIONS: Simulated trials are an innovative method for assessing trial design and acceptance from a patient-centric perspective, enabling specific improvements to be made prior to trial initiation. Incorporation of recommendations from simulated trials could enhance trial recruitment and retention, and optimise trial outcomes and data quality.

Diversity in the clinical presentation of generalized pustular psoriasis (GPP): A series of case vignettes from around the world.

A key principle of clinical studies and case reports is that they should reflect the demographics and epidemiology of the patient population concerned. Here, we have compiled a diverse group of clinical cases of generalized pustular psoriasis (GPP) to showcase the differences in GPP presentation in patients worldwide. We attempt to capture the broad spectrum of clinical presentations of GPP and showcase the diversity of the patient population. The patients included in this series are diverse in age, genetic background, skin phototype and medical history. Moreover, they present with a variety of clinical courses of GPP and different degrees of systemic involvement, and experience flares triggered by different inciting factors. The key learnings from this case series may support physicians in identifying and managing patients with this rare and multifaceted disease that can affect patients both physically and psychologically.

Engaging psoriasis patients in adherence and outcomes to topical treatments: A summary from the Symposium 'Tailoring topical psoriasis treatments to patients' needs and expectations' of the 30th EADV Congress 2021.

This article is based on a presentation given by authors at the Satellite Symposium titled 'Tailoring topical psoriasis treatments to patients' needs and expectations' held during the 30th European Academy of Dermatology and Venereology Congress. During this session, the factors affecting adherence and outcomes to topical treatments were presented, with a particular focus on the patients' point of view. Psoriasis is not just a skin condition. Psoriasis can cause negative psychosocial effects, such as depression and anxiety. The risk of suicidality in patients with psoriasis is higher than in the background population. Psychosocial comorbidities can be prevented by patient involvement in psoriasis management and need to be treated in a multidisciplinary manner. Adherence may be the largest barrier to treatment success with topical therapies. Improvement in several areas of disease management may lead to benefits in treatment adherence and hence clinical benefit. There are several treatment-related factors for non-adherence, such as patient dissatisfaction, side effects, treatment regimen or the drug vehicle. Delivering comprehensive treatment information to the patient will help develop realistic objectives and expectations. Patients need to be involved in the selection of treatment strategies, as psoriasis patients have various preferences for their use of topical treatments. A shared decision-making with the patient has been shown to improve medication adherence and treatment success. Prescribing therapy in line with a patient preference for treatment vehicle and improving the communication between healthcare professionals and patients may be key factors to maximize adherence. The calcipotriol (CAL) and betamethasone dipropionate (BDP) cream, a novel formulation of the CAL/BDP fixed-dose combination based on Poly-Aphron Dispersion (PAD) Technology, is a topical treatment of mild-to-moderate plaque psoriasis, including scalp psoriasis, that has high cosmetic acceptance and overall treatment satisfaction.

The role of topical therapies along the psoriasis patient journey: An overview from the Symposium 'Tailoring topical psoriasis treatments to patients' needs and expectations' of the 30th EADV Congress 2021.

This article summarizes a presentation titled 'The role of topical therapies along the psoriasis patient journey' held at the Satellite Symposium of the 30th European Academy of Dermatology and Venereology Congress. During this session, the role of topical treatments in the management of psoriasis was presented, with a particular focus on the current unmet needs and data gaps. Psoriasis plays a significant role in a patient's daily life, impacting them not only physically but also psychologically and socially. The disease burden increases with duration and severity. Topical therapies are the keystone of the management of psoriasis. About 70%-80% of patients present a mild-to-moderate form of psoriasis that can be successfully treated with topical agents. According to a German recommendation, patients with mild psoriasis should initiate a topical therapy in combination with skin care products. In the real-life setting, the calcipotriol/betamethasone dipropionate (CAL/BDP) fixed combination was the most prescribed topical treatment for beyond-mild patients in Germany, Spain and the United Kingdom. Healthcare professionals also often or very often prescribed topicals as an alternative to non-biologic systemics in certain situations, such as patient preference (51%), contraindication (50%) and to limit side effects (26%). Adjunctive topical therapy to patients using systemic therapy is used to optimize treatment outcomes and improving the quality of life for patients. Topical treatments can be also effective in severe forms of psoriasis. However, there are still some gaps and unmet needs on topical therapy. Ineffectiveness, patient dissatisfaction and adherence are the largest barriers to treatment success. Main strengths of topical treatments include the availability of various topical ingredients and galenics, the adaptability to different anatomical areas and the possible combination with phototherapy and systemics. Moreover, patients in specific situations can benefit from switching to topical treatments (e.g. pregnancy or surgery).

Psoriasis Involving Special Areas is Associated with Worse Quality of Life, Depression, and Limitations in the Ability to Participate in Social Roles and Activities.

Background: Psoriasis severity has traditionally been categorized as mild, moderate, and severe. Commonly, cut-offs for severe disease require a body surface area (BSA) involvement of ≥10% or a Psoriasis Area Severity Index (PASI) > 10. However, clinical experience challenges these traditional measures and requirements, as patients with less extensive psoriasis may have disease that severely impacts quality of life. Objective: The objective of the present study was to further explore the extent of patient burden when psoriasis affects special locations. Methods: A total of 69,190 individuals living in the U.S were invited to participate in a patient advocacy survey by telephone and or web interviews over the course of 3 years (2019-2021). The survey instrument consisted of validated patient-reported outcome measures, measuring disease-specific quality of life (Dermatology Life Quality Index, DLQI), depression (Patient Health Questionnaire (PHQ)-2 and (PHQ)-9), and the ability to participate in social roles and activities (PROMIS Ability to Participate in Social Roles and Activities (SF-4a). Chi-square tests were performed to explore association between psoriasis involvement on special locations and patient outcomes and multivariate logistic regression models were then constructed, to assess impact of having psoriasis on special locations patient outcomes, controlling for potential confounding factors. Results: A total of 4129 individuals completed the survey. 3594 (84.4%) of patients surveyed reported psoriasis involving special areas of the bodysuch as the scalp, face, hands, feet, or genitalia. Involvement of special areas is associated with worse quality of life and depression. 35-71% of patients with 10% or less total BSA involvement experienced a moderate-to-extremely large effect on these life function domains. When adjusting for age, sex, and body surface area, psoriasis involvement of a special location was associated with poorer patient reported outcomes, including a 46% less likelihood of reporting their skin disease as having "no or only a small effect on QoL," a 30% less likelihood of having a "normal l ability to participate in social roles and activities," and a 126% higher likelihood of f having depression. Conclusion: Real-world data presented here demonstrate that psoriasis involving special areas is associated with adverse life consequences, including poor quality of life and depression.

Safety Assessment of Conventional and Biological Systemic Therapy in Older Adults with Psoriasis, a Real-world Multicentre Cohort Study.

Optimal selection of systemic therapy in older adults with psoriasis can be challenging, due to sparse evidence-based guidance. This multicentre retrospective study investigated the safety of systemic therapy with causality assessment in a real-world cohort of older adults (≥ 65 years) with psoriasis. Data from 6 hospitals on (serious) adverse events were collected, causality assessment performed and incidence rate ratios calculated. Potential predictors for adverse events-occurrence were studied using multivariable logistic regression analysis. In total, 117 patients with 176 treatment episodes and 390 patient-years were included, comprising 115 (65.3%) and 61 (34.7%) treatment episodes with conventional systemic therapy and biologics/apremilast, respectively. After causality assessment, 232 of 319 (72.7%) adverse events remained and were analysed further, including 12 serious adverse events. No significant differences in incidence rate ratios were found between the systemic treatment types. In regression analysis, increasing age was associated with causality assessed adverse events-occurrence (odds ratio 1.195; p=0.022). Comorbidity, polypharmacy, and treatment type were not associated with causality assessed adverse events-occurrence. In conclusion, increasing age was associated with a higher causality assessed adverse events-occurrence. Causality assessed serious adverse events were rare, reversible and/or manageable in clinical practice. In conclusion, the safety profile of systemic antipsoriatic therapy within this population is reassuring.

Age-based treatment differences in and reluctance to treating older adults with systemic antipsoriatic therapy - a mixed-method pilot study.

BACKGROUND: Evidence-based guidance in older adults (≥65 years) with psoriasis is sparse and undertreatment might be present. OBJECTIVES: To assess prescribing patterns, comfort levels, barriers and needs of dermatologists when treating older adults with systemic antipsoriatic therapy. METHODS: A mixed-methods design was used including a survey among all Dutch dermatologists and residents, followed by semi-structured interviews. RESULTS: Most of the survey respondents applied systemic treatment to the same extent in older versus younger patients (n = 49; 67.1%) and weren't reluctant prescribing systemic therapy (n = 50; 68.5%) in older adults. However, 26% (n = 19) of the respondents treated older adults less often with systemic therapy compared to younger patients and 68.1% (n = 49) performed additional actions in older adults, e.g. intensified monitoring or dose reduction. Based on the survey and interviews (n = 10), the main reasons for these age-based treatment differences were comorbidity, comedication, and fear of adverse events. More evidence-based guidance, education, and time to assess older adults were identified as most important needs, especially regarding frailty screening. CONCLUSIONS: Age-based treatment differences in and reluctance to treating older adults with systemic antipsoriatic therapy were common. There is a need for more evidence-based guidance, education, and consultation time, to improve treatment in this growing population.

From Empirical to Pathogenesis-Based Treatments for Psoriasis.

Since the foundation of the European Society for Dermatological Research, pathogenesis of psoriasis has been studied by many research groups, focusing on various compartments of the skin. Understanding of the pathogenesis of psoriasis has evolved into a branching model of innate and acquired immunity. Insights in the genetics of psoriasis proved to be compatible with this model. Inspired by these insights, pathogenesis-based treatments have emerged with unprecedented efficacy and sustainability. In particular, the cytokine network harbors major treatment targets for biologics with TNF-α, the IL-17 family, IL-23 and, in the case of generalized pustular psoriasis, IL-36. Furthermore, the Jak TYK2, PDE-4, and AHR are targets for new small molecules in the treatment of psoriasis. Psoriasis research is a showcase par excellence of translational medicine, resulting in pathogenesis-based treatments.

The association between acne care provision and quality of life: A cross-sectional survey.

BACKGROUND AND AIMS: It has been suggested that professional acne care can be effective not only in reducing clinical signs but also in improving quality of life (QOL). This study aims to reach a better understanding of the association between QOL and professional acne care. The study also investigates other factors that might influence QOL such as age, gender, and acne severity. METHODS: Between 2019 and 2020, a cross-sectional survey-based study was conducted among 362 acne patients. Data were collected by the Cardiff Acne Disability Index (CADI) and a Global QOL scale. Analysis of covariance (ANCOVA) and post hoc comparisons were conducted to analyze the association between professional acne care and health-related QOL. RESULTS: No statistically significant differences were found in QOL measured by CADI among patients visiting the four investigated acne caregivers (mean CADI score: dermatologist, 4.49; GPs, 4.42; dermal therapist, 4.07; beautician, 4.20, P = .24). However, the impact of the treatment on the QOL, which was measured by the level of Global QOL improvement before and after care, demonstrated a statistically significant improvement when attending a dermatologist, compared to the care provided by beauticians (Global QOL improvement: dermatologist, 1.50; GP, 1.01; dermal therapist, 1.10; beautician, 0.54, P = .05). Females experienced a more impaired acne-related QOL than males (P = .05), and increased acne severity was associated with a more impaired QOL (P < .05). CONCLUSIONS: This study delineated factors that influence QOL in acne patients. As the QOL was not associated with the type of caregiver, the greatest QOL improvement before and after care was achieved after medical treatment by the dermatologist. Females and individuals dealing with more severe types of acne experienced a more impaired acne-related QOL. It is recommended to take these factors into account in acne management to optimize professional treatment in line with patient needs.

Serum drug levels and anti-drug antibodies in the context of dose tapering by interval prolongation of adalimumab, etanercept and ustekinumab in psoriasis patients: results of the CONDOR trial.

BACKGROUND: Biologics for psoriasis are registered in standard dosages. In patients with low disease activity, reduction of the dose by interval prolongation can prevent overtreatment, and lower risks and costs. However, fear for increased anti-drug antibody (ADA) formation due to interval prolongation of biologics is an important barrier. OBJECTIVE: To investigate the course of serum drug concentrations, ADA levels, and predictors for successful dose reduction of adalimumab, ustekinumab, and etanercept for psoriasis. METHODS: Patients were randomized to dose reduction (DR) or usual care (UC) and followed for one year. The course and extent of detectable ADA levels were expressed as proportions/relative risks for DR vs. UC. Association of baseline characteristics with successful tapering was investigated with log-binomial regression analysis. RESULTS: In total, 118 patients were included. In adalimumab-treated patients, no significant difference in the proportion of patients with relevant ADA levels in DR vs. UC was seen. For ustekinumab, relevant ADA development was absent in both groups. Baseline trough levels were not predictive for successful DR. CONCLUSIONS: Immunogenicity may not increase by interval prolongation in psoriasis patients with low disease activity. This pilot provides important and reassuring insight into the pharmacological changes after dose tapering of adalimumab, etanercept, and ustekinumab.