Psoriasis (Auckland, N.Z.)最新文献

Introduction: Psoriasis is a chronic immune-mediated disease that significantly impacts patients clinically and psychologically. Physician-assessed severity measures, including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Physician Global Assessment (PGA), often fail to capture patient-reported outcomes, particularly when clinical improvement and perceived quality-of-life gains are misaligned.

Purpose: To clarify the association between clinical improvements and Dermatology Life Quality Index (DLQI) outcomes, identify predictors of substantial DLQI improvement (≥90% reduction), and explore reasons for suboptimal DLQI responses in patients achieving skin clearance.

Methods: In this 12-week prospective study, 551 psoriasis patients were enrolled at Shanghai Skin Diseases Hospital. Data on demographics, clinical severity (PASI, BSA, and PGA), DLQI scores, and treatment modalities were collected. Logistic regression analyses were employed to assess the dose-response relationships between improvements in clinical parameters and DLQI reduction, and to identify factors of suboptimal DLQI improvement among patients achieving significant skin clearance.

Results: Median DLQI improved significantly (8.0 to 3.0) at week 12, with 24.1% of patients achieving ≥90% DLQI reduction. Strong dose-response associations existed between clinical severity improvements (PASI, BSA, PGA) and DLQI gains. PASI₇₅ responders were significantly more likely to achieve substantial DLQI improvement (OR = 2.48, 95% CI: 1.51-4.07). However, only 33.3% of PASI₇₅ achievers reached ≥90% DLQI improvement. Early clinical response (as early as week 4) strongly predicted superior DLQI outcomes. Female sex, older age, lower baseline DLQI scores, and shorter disease duration were associated with achieving high skin clearance but suboptimal DLQI improvement.

Conclusion: Early clinical response effectively predicts substantial DLQI improvement, whereas demographic and disease-related factors help identify patients at risk for suboptimal quality-of-life gains despite significant skin clearance. These insights support personalized therapeutic strategies aimed at improving patient satisfaction beyond skin clearance alone.

Background: Genetic susceptibility to psoriasis involves multiple loci, including TYK2 (Tyrosine Kinase 2), which is associated with various autoimmune diseases. However, its specific role and mechanisms in psoriasis remain unclear. This study aimed to identify psoriasis-associated proteins using Summary-based Mendelian Randomization (SMR) and to explore their regulatory mechanisms.

Methods: SMR analysis integrating pQTL data was conducted to identify proteins linked to psoriasis, revealing ICAM1 (Intercellular Adhesion Molecule 1) as a potential pathogenic factor. A key SNP, rs34536443 (P1104A), located in TYK2, was found to regulate ICAM1. To assess its function, THP-1 cells carrying the TYK2-P1104A mutation were generated, and ICAM1 and cytokine expression were analyzed following LPS stimulation. The effect of the TYK2 inhibitor Deucravacitinib was tested in an imiquimod (IMQ)-induced psoriasis mouse model.

Results: SMR identified ICAM1 as a causal protein for psoriasis, regulated by the TYK2 SNP rs34536443. In TYK2-P1104A mutant THP-1 cells, LPS-induced ICAM1 expression was significantly reduced, with ICAM5 unaffected. The mutation also suppressed IL-1β, TNF-α, IL-6, and IL-18 expression, suggesting anti-inflammatory effects. Single-cell RNA-seq revealed enrichment of TYK2, ICAM1, and ICAM5 in dendritic cells and monocytes. In vivo, Deucravacitinib significantly downregulated ICAM1 in the IMQ-induced psoriasis model, with minimal effect on ICAM5.

Conclusion: This study identifies ICAM1 as a key mediator in psoriasis via SMR analysis and implicates the TYK2 SNP rs34536443 in its regulation. The TYK2-P1104A variant attenuates ICAM1 and cytokine expression, and Deucravacitinib downregulates ICAM1 in vivo. These findings provide mechanistic insights into the TYK2-ICAM1 axis and support the therapeutic potential of TYK2 inhibitors for psoriasis.

Psoriasis is a chronic inflammatory immune-mediated disease that affects 1-3% of the worldwide population. It is now known that interleukin IL-17F and IL-17A have a role in the pathophysiology of immune-mediated inflammatory disorders, such as psoriasis. According to recent data, neutralizing IL-17A and -17F together may be more effective than neutralizing IL-17A alone in treating psoriasis. Bimekizumab is a humanized IgG1 monoclonal antibody that selectively binds and diminishes the biological functions of both IL-17A and -17F. Current biologics for treating psoriasis lack complete skin clearance and reliable quick response. Bimekizumab's efficacy was evaluated in four randomized controlled trials involving around 2,200 patients with plaque psoriasis. The results showed that bimekizumab outperformed placebo, adalimumab, secukinumab, and ustekinumab, with higher response rates for both PASI 90 and PASI 100 at 16 weeks. Furthermore, Bimekizumab has shown superiority in direct comparative clinical studies (RCTs) performed. When compared to other biologics, Bimekizumab has shown a more rapid onset in terms of rapid response and better efficacy with a comparable safety profile as the most frequent adverse events include oral candidiasis, upper respiratory tract infections, and nasopharyngitis. These features of Bimekizumab provide advantages for the patients in term of better efficacy with rapid response and safe profile which ultimately affect the selection and treatment algorithm for management of plaque psoriasis.

Purpose: Psoriasis vulgaris is a chronic systemic inflammatory disease that imposes a significant physical, emotional, and social burden on affected individuals. There is a growing recognition of the importance of comprehensive monitoring and management to optimize treatment outcomes, particularly with the advent of advanced systemic therapies. This study aims to characterize the prevalence of laboratory monitoring and associated costs in persons with psoriasis undergoing systemic treatment. A specific focus was placed on the differences by treatment modality, patient characteristics, and economic burden to the payers.

Patients and methods: A retrospective longitudinal analysis was conducted using German health insurance data from the DAK-Gesundheit. The study population included persons diagnosed with psoriasis who received systemic therapies between 2016 and 2020. Laboratory service utilization and costs were assessed during the initiation and course of treatment, factoring in demographic parameters and comorbidities.

Results: Among 62,063 persons with psoriasis, 8018 (12.9%) were identified as having received systemic treatment, which of 92.5% utilized at least one laboratory service. The average annual laboratory monitoring cost per person was higher for those on biologic therapies (57.88 €) compared to systemic treatments (23.70 €). Laboratory service utilization and costs were associated with the comorbidity index (CCI) and age.

Conclusion: Biologic therapies for psoriasis induce considerably higher monitoring costs than non-biological systemic drugs. Age and CCI were main predictors for higher utilization of laboratory services, indicating a medical rationale to perform more lab screenings in risk groups for safety events. The laboratory costs add to the higher drug costs of biologicals but need to be related to the benefits from treatment. Furthermore, the monitoring costs are far lower than the drug costs and thus may not be major decision drivers.

Purpose: Elderly patients with age ≥65 years represent an increasing percentage of the population with moderate-severe psoriasis. The definition of "frail elderly" is not easily framed, generally meaning a patient with unstable homeostasis. To date, there is no study in the literature examining possible differences between frail and non-frail elderly with psoriasis being treated with tildrakizumab.

Patients and methods: The present multicentre retrospective study evaluated the effectiveness, drug survival and safety up to 2 years of treatment with tildrakizumab in the elderly (≥65 years) comparing frail and non-frail patients. Frail patients were defined as those with: i) 2 major comorbidities, or 1 major comorbidity and low economic level ii) and/or 2 of the following 5 parameters: weight loss, weakness, sluggishness, low activity level, and exhaustion.

Results: A total of 217 patients aged ≥65 years were enrolled, of whom 89 (41%) were grouped in the frail patient category. In the entire population, 2-year drug survival was ≥80%, and PASI 90 and ≤2 was achieved in 75% and 87.5% of patients, respectively. No difference in effectiveness or safety was found between frail and non-frail populations. Adjusting for baseline characteristics at Cox-regression, frail patients did not show a greater risk of discontinuation (HR 0.51, p=0.091).

Conclusion: Tildrakizumab showed good safety and effectiveness at 2 years in the elderly population with or without frailty, confirming it as a possible treatment of choice in psoriatic patients with significant comorbidities and older frail patients who deserve systemic treatments.

Moderate to severe psoriasis has been reported as an independent risk factor for IgA nephropathy (IgAN). IgAN is characterized by episodic microscopic hematuria, which can progress to end-stage renal disease (ESRD). Managing therapeutic interventions for psoriasis patients requiring dialysis due to ESRD presents significant challenges. We present a case of severe plaque psoriasis in a patient concurrently diagnosed with IgAN who is dependent on hemodialysis. Over the past two months, his condition has worsened without any identifiable triggers. Physical examination revealed generalized scaly plaques on the scalp, trunk, and extremities, resulting in a Psoriasis Area Severity Index (PASI) score of 19.2. Laboratory tests confirmed end-stage renal insufficiency, with no other abnormalities detected. Consequently, the patient was prescribed subcutaneous secukinumab following a standard regimen. He achieved complete resolution of symptoms after eight weeks of treatment and experienced no recurrence during a one-year follow-up. His kidney-related parameters remained stable during secukinumab therapy. To summarize, this case report discusses a patient with severe psoriasis who also has concurrent IgAN and ESRD, successfully treated with secukinumab. It reinforces the rapid efficacy and enduring safety of secukinumab in managing psoriasis in hemodialysis-dependent patients with IgAN comorbidity. Zeno Fratton et al has reported that an interleukin (IL)-17A/F inhibitor effectively treats moderate-to-severe psoriasis in patients with chronic kidney disease (CKD). However, further studies are necessary to develop evidence-based guidelines for biologic selection within this vulnerable population.

Erythrodermic psoriasis (EP) is an uncommon and severe form of psoriasis, which exhibits a Th1/Th17/TNF inflammatory pattern. Most patients with EP experience systemic symptoms that necessitate systemic treatments. These treatments include conventional systemic drugs (such as acitretin, cyclosporin A, and methotrexate), biologics (including IL-17, IL-12/23, and TNF-α inhibitors), and small molecule drugs (such as apremilast and JAK inhibitors). Evaluating the severity of EP is critical for determining appropriate treatment strategies. According to an innovative EP severity evaluation approach, patients exhibiting two or more clinical features-fever, exudation, or lymphadenopathy-are classified as having moderate-to-severe EP, while those with one or none of these symptoms are categorized as having mild EP. Mild EP can often be managed with monotherapy using acitretin, methotrexate, or biologics, such as IL-17 or IL-12/23 inhibitors, excluding TNF-α inhibitors. For moderate-to-severe EP, cyclosporine A and biologics, particularly IL-17 or IL-12/23 inhibitors, are recommended. Combination therapies are considered when monotherapies prove ineffective. These may involve combining a biologic with a conventional systemic drug or using two to three conventional systemic drugs together to enhance efficacy. Supportive care plays a critical role in alleviating the discomfort associated with skin lesions and other complications. Additionally, treatments should be tailored to address specific comorbidities, often requiring multidisciplinary collaboration. In our comprehensive review, we summarized the current evidence on therapeutic options for EP, including details on dosages, treatment durations, efficacy, and adverse events. Additionally, we incorporated new evidence on the use of acitretin, biologics, and JAK inhibitors for EP. We also introduced, for the first time, a practical management algorithm based on severity evaluation to guide the appropriate treatment of EP.

Introduction: There is a dispute as to whether patients with psoriasis have impaired kidney function. We aimed to assess several recognized and experimental markers of glomerular filtration and tubular function in such patients to find out whether they have decreased kidney function.

Methods: The study involved 60 patients with psoriasis and 30 volunteers without dermatoses. The following molecules were analyzed by ELISA: serum creatinine, cystatin C, beta-trace protein, albumins, uromodulin; urinary albumins, cystatin C, alpha-1-microglobulin, beta-2-microglobulin, uromodulin, klotho, and fatty acid-binding protein 1, and nephrin.

Results: The following absolute values of markers concentrations were measured in patients, respectively: serum-1.13 (0.6-1.9)mg/dl, 4.511 (2.356-10.31)mg/l, 19.8 (2.8-48)ng/mL, 4.2 (1.9-8.85)g/dl, 212.3 (32.35-583.9)ng/mL, urine-5 (3-39)g/dl, 24096 (79.94-99020)ng/mL, 0.9342 (0.2088-6.213)ng/mL, 22.65 (0.85-105.8)ng/mL, 6.388 (0.8960-15.94)ng/mL, 0.08 (0.002-0.387)ng/mL, 1.773 (1.706-2.146)ng/mL, 0.128 (0.095-0.298)ng/mL. The patients had significantly lower serum albumin concentration (p<0.001) and higher urinary albumin (p<0.05), significantly higher serum cystatin C (p<0.01), and absolute urinary nephrin (p<0.05). There was no difference between patients and controls in terms of serum creatinine or beta trace protein concentration (p>0.05). There were no significant differences in the concentration of the tubular markers (urinary cystatin C, alpha-1-microglobulin, beta-2-microglobulin, klotho, and fatty acid-binding protein 1) between patients and controls, except for serum and urinary uromodulin, which were significantly lower in patients (p<0.01, p<0.001, respectively). We found no significant correlations between the investigated markers' concentration and clinical or demographic parameters (p>0.05).

Discussion: Despite the differences between patients and controls in terms of glomerular filtration markers, the median values of markers' concentration were within normal limits. Based on the assessment of the markers, it does not seem that impaired glomerular and tubular function occurs more frequently in patients with psoriasis. Nevertheless, due to the higher prevalence of diabetes mellitus and arterial hypertension in psoriatics and nephrotoxic properties of antipsoriatic drugs - caution must be exercised and easy screening tools should be considered.

Purpose: Epidemiological and health care data on generalized pustular psoriasis (GPP) show large differences in literature. This study assessed GPP epidemiology, comorbidities and health care in Germany.

Patients and methods: Nationwide population-related German claims data were analyzed using different case definitions for internal validation.

Results: In 2019, the prevalence of GPP in Germany in adults ranged from 8 to 39 and incidence from 1 to 15 persons per 100,000. Prevalence was higher in women and increased with age. Thirty-three percent had at least one other psoriatic ICD-10 code. People with GPP had significantly more skin diseases as well as cardiovascular and mental diseases than persons without psoriasis/GPP. The average annual drug costs per capita were € 2050 and were highest in those receiving biologicals (€ 15,524). Marked differences in treatment by specialist were observed.

Conclusion: Acknowledging that the observed frequency or costs associated with GPP may be underestimated due to a few inherent limitations is important. Differences in GPP coding behavior and diagnostic accuracy may contribute to variations in epidemiology. The high disease burden is reflected by high annual costs and by significant comorbidity.

Purpose: Tobacco smoking is an unhealthy behavior associated with the onset, severity, and treatment response of psoriasis. However, evidence regarding the impact of tobacco smoking on the relapse of psoriasis remains limited. This study aims to examine the relapse condition in psoriasis patients and explore the association between tobacco smoking and psoriasis relapse.

Patients and methods: We conducted an observational study with 551 psoriasis patients recruited from 2022 to 2024 in Shanghai Skin Disease Hospital. A structured questionnaire and physical examination were used to collect data at baseline, week 12, week 24 and week 48. PASI50 and PASI75 were used to evaluate the improvement of psoriasis patients after treatment at week 12, and disease relapse was defined as the loss of 50% PASI improvement during clinical remission after the achievement of PASI50 or PASI75 at week 12.

Results: 75.7% of the 551 psoriasis patients were males, with an average age of 45.8 years, and 282 (51.2%) were tobacco smokers. 41.2% and 61.6% of psoriasis patients with PASI50 achievement at week 12 encounter disease relapsed at week 24 and 48, respectively, while for patients with PASI75 achievement at week 12, the relapse rate was 27.6% and 51.7% at week 24 and 48, respectively. Logistic regression indicated that patients with tobacco smoking had a higher relapse rate, especially among those with PASI75 achievement at week 12. The odds ratio was 2.10 (95% CI: 1.17-3.78) and 1.84 (95% CI: 1.07-3.14) at week 24 and week 48 respectively, even after adjusting for potential confounding factors. Moreover, patients with longer smoking duration and more daily cigarette consumption had higher relapse rate.

Conclusion: Tobacco smoking was positively correlated with the relapse, especially among those with longer smoking duration and more daily cigarette consumption. Therefore, patients with psoriasis should quit smoking to reduce the risk of relapse.