Efficacy and safety of biological agents to treat patients with palmoplantar pustulosis: A systematic scoping review.

BACKGROUND: Palmoplantar pustulosis (PPP), a chronic, recurrent pustular dermatosis associated with erythema, scales, and sterile pustules on the palms and soles, is commonly encountered in dermatology clinics. Whether PPP is a variant of psoriasis or a distinct condition is still debated. Although biological agents have been successfully used to treat moderate-to-severe psoriasis, existing literature on PPP is limited to case reports or small case series. The lack of well-documented clinical studies makes it difficult to select the ideal treatment for this condition. This review aims to discuss the efficacy and safety of biological agents in PPP treatment based on randomized controlled trials with the hope of inspiring dermatologist clinicians to propose new therapeutic approaches. OBJECTIVES: This review aims to obtain high-level evidence to assess the efficacy and safety of biological agents in the treatment of patients with PPP. METHODS: We searched the PubMed, Embase, and Cochrane databases up to May 18, 2023, for high-quality randomized controlled trials that reported at least one adverse event after PPP treatment with biological agents in patients > 18 years of age. RevMan 5.3 software was used for the meta-analysis. RESULTS: Nine trials involving 799 participants were included in the analysis. We used ppPASI 75 as the primary efficacy measure. Anti-IL-23 and anti-IL-17A agents afforded 4.14-fold and 1.95-fold better outcomes than placebo treatment at weeks 16 and 12, respectively (P-value = 0.009, RR = 4.14, 95% confidence interval [CI; 1.43-11.98]; P-value = 0.02, RR = 1.95, 95% CI [1.11-3.42]). Moreover, anti-IL-23 agents at a dose of 100 mg were more effective than at 200 mg, indicating that 100 mg may be the best dose for anti-IL-23 agents. Next, we investigated the safety of biological agents for PPP treatment. The incidence of total adverse events (AEs) was 1.25 times higher for biological agents than for controls, indicating a good safety profile (RR = 1.25, P-value ＜ 0.00001, 95% CI [1.13, 1.37]). Additionally, we divided the common AEs into 16 categories and found that anti-IL-23 agents were more likely to induce infections. In conclusion, we evaluated safety and efficacy in a comprehensive comparison and found that anti-IL-23 agents conferred good clinical efficacy with a low incidence of AEs and could be recommended with caution. LIMITATIONS: Only a few relevant, high-quality, randomized controlled trials were included in the study. CONCLUSION: This study showed that biological agents can be used to treat patients with PPP with good efficacy; however, AEs cannot be ignored. Multi-center, high-quality clinical studies with large sample sizes are needed to further evaluate the effects and safety of biological agents in PPP treatment.

Aberrant promoter methylation of Wnt inhibitory factor-1 gene is a potential target for treating psoriasis.

Psoriasis is a chronic inflammatory skin disease mediated by immune and complex genetic factors. The wingless-related integration site (Wnt) signaling pathway plays a critical role in psoriasis, but how the Wnt pathway is regulated in psoriatic skin and whether it can be exploited for therapeutic benefits is unclear. By comparing biopsies from healthy and psoriatic skin, we found that Wnt inhibitory factor 1 (WIF1), an inhibitor of Wnt signaling, showed reduced expression at both mRNA and protein levels in psoriatic skin. We then quantified methylation of the WIF1 gene promoter by DNA methylation sequencing and found that the WIF1 promoter region was hypermethylated. We further showed that recombinant WIF1 injection ameliorates the imiquimod (IMQ) mouse model of psoriasis. We also revealed that treatment with the DNA methylation inhibitor, decitabine, inhibited proliferation of immortalized human keratinocytes (HaCaT) in a psoriasis-like inflammatory environment. Finally, we applied decitabine to the IMQ mouse model and demonstrated that treatment of mice with decitabine ameliorates the disease. Therefore, our study reveals that methylation of the WIF1 gene is associated with the pathogenesis of psoriasis, and suggests that pharmacological targeting of DNA methylation is a potential treatment strategy for psoriasis.

Epidemiology of mental health comorbidity in patients with psoriasis: An analysis of trends from 1986 to 2019.

BACKGROUND: The prevalence of mental disorders such as depression, anxiety, and suicide has increased in patients with psoriasis, although no study has systematically analyzed the epidemiology worldwide. OBJECTIVE: To explore the prevalence and incidence of psoriasis with comorbid mental disorders (i.e., depression, anxiety, and suicide). METHODS: Five databases from establishment through May 2022 were searched. Stata SE 15.1 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies. RESULTS: We evaluated 56 studies in our research. The prevalence of depression, anxiety, and suicide in adults with psoriasis was 20%, 21%, and 0.77%. Patients with psoriasis in North America had a higher prevalence of depression and suicide, whereas those in South America had a higher prevalence of anxiety. The incidence of depression, anxiety, and suicide was 42.1, 24.7, and 2.6 per 1000 person-years in adults with psoriasis, respectively. LIMITATIONS: All of the included studies were published in Chinese and English, causing a degree of selection bias. CONCLUSION: These findings demonstrate the incidence and prevalence of comorbid mental disorders in patients with psoriasis, which may raise awareness among physicians and patients regarding the mental problems associated with psoriasis.

Adverse events associated with anti-IL-17 agents for psoriasis and psoriatic arthritis: a systematic scoping review.

Background: Anti-interleukin (IL)-17 biological agents (BAs) have significant efficacy in the treatment of psoriasis and psoriatic arthritis; however, adverse events (AEs) are common, and their safety has not been systematically evaluated. Objectives: The purpose of this systematic review and meta-analysis was to summarize the number and corresponding rates of AEs caused by anti-IL-17 BAs in patients with psoriasis and psoriatic arthritis to improve clinical decision-making regarding their use. Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were independently searched by three authors for articles on the treatment of psoriasis with anti-IL-17 BAs that were published before March 1, 2022, and included at least one AE. Dichotomous variables and 95% confidence intervals (CI) were analyzed using R software (version 4.1.3) and the Meta and Metafor software packages. Funnel plots and meta-regression were used to test for the risk of bias, I2 was used to assess the magnitude of heterogeneity, and subgroup analysis was used to reduce heterogeneity. Results: A total of 57 studies involving 28,424 patients with psoriasis treated with anti-IL-17 BAs were included in the meta-analysis. Subgroup analysis showed that anti-IL-17A (73.48%) and anti-IL-17A/F (73.12%) BAs were more likely to cause AEs than anti-IL-17R BAs (65.66%). The incidence of AEs was as high as 72.70% with treatment durations longer than one year, and long-term use of medication had the potential to lead to mental disorders. Infection (33.16%), nasopharyngitis (13.74%), and injection site reactions (8.28%) were the most common AEs. Anti-IL-17 BAs were most likely to cause type α (33.52%) AEs. Type δ AEs (1.01%) were rarely observed. Conclusions: Anti-IL-17 BAs used for the treatment of psoriasis and psoriatic arthritis caused a series of AEs, but the symptoms were generally mild.

Efficacy and safety of Chinese herbal medicine for atopic dermatitis: Evidence from eight high-quality randomized placebo-controlled trials.

Background: The use of Chinese herbal medicine (CHM) for the treatment of atopic dermatitis (AD) has gained attention. This quantitative study systematically evaluated the efficacy and safety of CHM for the treatment of AD in eight high-level clinical trials, resulting in a high level of clinical evidence. Methods: Several databases were searched, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chongqing VIP Chinese Science (VIP), and Wanfang Database. High-quality randomized controlled trials (RCTs) comparing CHM with placebo were included. The 95% confidence interval (CI) of the risk ratio (RR) was calculated using software (RevMan 5.3) and a meta-analysis was performed. Evidence level evaluation using GRADE Profiler 3.6. Results: In total, 662 patients (322 in the experimental group and 340 in the control group) were included. The response rate of the Eczema Area and Severity Index (EASI) -90 was higher in the CHM group than in the placebo group (RR, 3.72; 95% CI, 1.76 to7.83; p = 0.01). Furthermore, the scoring of atopic dermatitis (SCORAD) (RR, -10.20), body surface area (BSA) (RR, -2.01), surface damage score (RR, -2.25), visual analog scale (VAS) (RR, -1.90), and sleep score (RR, -2.16), improvement of investigator's global assessment (IGA) (RR, 2.94) improved in the CHM group. The results showed no statistical difference between CHM and placebo (MD, -0.47; 95% CI, -1.30, 0.37; p = 0.27) in improving the Dermatology Life Quality Index (DLQI) or children's DLQI (CDLQI). There was also no significant difference in the IgE level between the two groups (MD, -62.76; 95% CI, -809.58, 684.05; p = 0.87). However, the adverse events (AEs) rate was slightly higher in patients treated with CHM than in those treated with placebo (RR, 1.42; 95% CI, 1.06-1.90; p = 0.02). Conclusion: CHM improved the size and severity of the skin lesions and sleep quality in patients with AD. Comparing the adverse effects between the two groups, CHM is safe. However, CHM does not improve the quality of life or the patient's IgE levels.

Cutaneous allergic reaction to subcutaneous vitamin K1: A case report and review of literature.

BACKGROUND: Vitamin K1 (phytomenadione) is a fat-soluble naturally occurring vitamin that is widely used to treat certain coagulation disorders. Adverse cutaneous reactions to vitamin K1 can occur; however, owing to its low incidence and considerable variability in presentation and morphology, its diagnosis can be easily overlooked. Managing these reactions may be challenging for patients and clinicians. Therefore, reviewing the adverse cutaneous reactions to vitamin K1 is important. CASE SUMMARY: Here we report the case of a 50-year-old woman with no pre-existing hepatic disease who developed a cutaneous allergic reaction to subcutaneous vitamin K1 that presented as localized eczematous plaques at the vitamin K1 injection site. The eruption developed within 5 d of the injection and persisted for 32 mo despite treatment with topical and intralesional steroids. Eczema was diagnosed based on the results of the pathological examination, immunohistochemical staining, and a skin biopsy. The patient was advised to take herbal medicines orally twice daily. After treatment and follow-up, the patient's eczematous urticarial plaques improved and her condition stabilized. CONCLUSION: Here we present the first case of a cutaneous allergic reaction to subcutaneous vitamin K1 that was successfully treated with Chinese medicine.

Exploration of and insights into advanced topical nanocarrier systems for the treatment of psoriasis.

Psoriasis is a chronic inflammatory skin disease with an underlying autoimmune pathogenesis that has brought great distress to patients. Current treatment options include topical therapy, systemic therapy, and phototherapy. By disrupting the stratum corneum, nanocarriers have unique advantages in allowing drug carriers to be tailored to achieve targeted drug delivery, improve efficacy, and minimize adverse effects. Furthermore, despite their limited success in market translatability, nanocarriers have been extensively studied for psoriasis, owing to their excellent preclinical results. As topical formulations are the first line of treatment, utilize the safest route, and facilitate a targeted approach, this study, we specifically describes the management of psoriasis using topical agents in conjunction with novel drug delivery systems. The characteristics, advantages, weaknesses, and mechanisms of individual nanocarriers, when applied as topical anti-psoriatic agents, were reviewed to distinguish each nanocarrier.