Association Between Serum Total IgE Levels and Clinical Response to Omalizumab for Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical response to omalizumab. OBJECTIVE: We aimed to determine the association between baseline total serum IgE levels and the effects of omalizumab in patients with CSU. METHODS: PubMed, Web of Science, Scopus, and Cochrane Library were systematically searched for relevant studies from inception to August 23, 2022. The research protocol was registered on PROSPERO (CRD42022355592). No language restrictions were applied. A random-effects model was used for meta-analysis. RESULTS: Ten interventional studies, including 1 randomized controlled trial, were included in the final meta-analysis, and a total of 866 patients with CSU were included. A pooled analysis showed significantly higher serum total IgE levels in complete responders (CRs) than in nonresponders (NRs) (mean difference [MD]: 56.509 IU/mL; 95% confidence interval [CI]: 24.230-88.789) and in partial responders (PRs) than in NRs (MD: 62.688 IU/mL; 95% CI: 32.949-92.427), but no significant difference was detected between CRs and PRs. The mean total IgE levels for CRs, PRs, and NRs were 163.154, 179.926, and 51.535 IU/mL, respectively. Further, the serum total IgE levels in early CRs were significantly higher compared with late CRs (MD: 55.194 IU/mL; 95% CI: 13.402-96.986). The sensitivity analyses with the leave-one-out method validated the robustness of all findings. CONCLUSIONS: This systematic review and meta-analysis provide convincing evidence that pretreatment total serum IgE levels in patients with CSU are associated with clinical responses to omalizumab.

A Review of the Systemic Treatment of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are uncommon but life-threatening diseases mostly caused by drugs. Although various systemic immunomodulating agents have been used, their therapeutic efficacy has been inconsistent. This study aimed to provide an evidence-based review of systemic immunomodulating treatments for SJS/TEN. We reviewed 13 systematic review and meta-analysis articles published in the last 10 years. The use of systemic corticosteroids and IVIg is still controversial. An increasing number of studies have suggested the effectiveness of cyclosporine and biologic anti-TNF-α in recent years. There were also some promising results of combination treatments. Further large-scale randomized controlled trials are required to provide more definitive evidence of the effectiveness of these treatments. The pathogenesis of SJS/TEN has been elucidated in recent years and advances in the understanding of SJS/TEN may inspire the discovery of potential therapeutic targets.

Effectiveness and Safety of Immunosuppressants and Biological Therapy for Chronic Spontaneous Urticaria: A Network Meta-Analysis.

Chronic spontaneous urticaria (CSU) is the most common phenotype of chronic urticaria. We compared treatment effects and safety profiles of the medications in patients with CSU. We searched PubMed, MEDLINE, and Web of Science for randomized control trials (RCTs), from 1 January 2000 to 31 July 2021, which evaluated omalizumab and immunosuppressants. Network meta-analyses (NMAs) were performed with a frequentist approach. Outcome assessments considered the efficacy (Dermatology Life Quality Index (DLQI) and weekly urticaria activity score (UAS7)) and tolerability profiles with evaluations of study quality, inconsistencies, and heterogeneity. We identified 14 studies which we included in our direct and indirect quantitative analyses. Omalizumab demonstrated better efficacy in DLQI and UAS7 outcomes compared to a placebo, and UAS7 assessments also demonstrated better outcomes compared to cyclosporine. Alongside this, omalizumab demonstrated relatively lower incidences of safety concerns compared to the other immunosuppressants. Cyclosporin was also associated with higher odds of adverse events than other treatment options. Our findings indicate that omalizumab resulted in greater improvements in terms of the DLQI and UAS7 with good tolerability in CSU patients compared to the other immunosuppressants.

Efficacy of local prostaglandin analogues for vitiligo treatment: a systematic review and meta-analysis.

BACKGROUND: Vitiligo is a common cutaneous depigmentation disorder. Although multiple treatment options are available, no single modality is satisfactory for all patients. Several studies have demonstrated that prostaglandin analogues can potentially treat cutaneous depigmentation, but the evidence is limited to their inconsistent study design. RESEARCH DESIGN & METHODS: A systematic review was performed for studies published before 29 June 2021, in PubMed, Embase, Web of Science, or the Cochrane Library. The primary outcome of pooled analysis was the repigmentation efficacy of local prostaglandin analogues compared with other therapies for vitiligo. RESULTS: Six randomized controlled trials (RCTs) and three non-RCTs were included in this systematic review, and seven studies among them were used for the meta-analysis. The pooled analysis demonstrated that local prostaglandin analogues could significantly increase repigmentation along with narrowband ultraviolet B phototherapy compared with phototherapy alone. Furthermore, the repigmentation efficacy of topical prostaglandin analogues was not significantly different from that of topical tacrolimus. In summary, local prostaglandin analogues either used alone or as add-on therapy could be safe and effective therapies for vitiligo.

Risk of ischaemic heart diseases and stroke in behçet disease: A systematic review and meta-analysis.

BACKGROUND: Behçet disease (BD) is a systemic vasculitis. In addition to the mucocutaneous lesions, the vascular injury of pathophysiology in BD is theoretically correlated with cardiovascular diseases. This study aimed to elucidate the association of BD with ischaemic heart diseases (IHDs) and stroke. METHODS: A systematic search of PubMed, Embase, Web of Science and Cochrane Library databases was performed for all relevant observational studies from database inception until 10 July 2021. No language restriction was applied. A random-effects model was used for meta-analysis. RESULTS: A total of six observational studies consisting of three cohort studies, two cross-sectional studies and one study with both study designs were adopted in the meta-analysis. The numbers of patients with BD and healthy controls were 9,813 and 41,802, respectively. The pooled analysis demonstrated no significant association between BD and IHD. By contrast, we found that patients with BD had a significantly higher risk of stroke (adjusted hazard ratio, 2.083; 95% confidence interval, 1.339-3.240; p = 0.001) than healthy controls. We observed substantial heterogeneity across studies in few meta-analyses, but no significant publication bias was detected in any of the meta-analyses. CONCLUSIONS: BD was significantly associated with stroke but not IHD. Physicians should be aware of possible vascular and neurological complications during care of patients with BD.

Blimp-1 Upregulation by Multiple Ligands via EGFR Transactivation Inhibits Cell Migration in Keratinocytes and Squamous Cell Carcinoma.

B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional repressor and plays a crucial role in the regulation of development and functions of various immune cells. Currently, there is limited understanding about the regulation of Blimp-1 expression and cellular functions in keratinocytes and cancer cells. Previously we demonstrated that EGF can upregulate Blimp-1 gene expression in keratinocytes, playing a negative role in regulation of cell migration and inflammation. Because it remains unclear if Blimp-1 can be regulated by other stimuli beyond EGF, here we further investigated multiple stimuli for their regulation of Blimp-1 expression in keratinocytes and squamous cell carcinoma (SCC). We found that PMA, TNF-α, LPS, polyIC, H2O2 and UVB can upregulate the protein and/or mRNA levels of Blimp-1 in HaCaT and SCC cells. Concomitant EGFR activation was observed by these stimuli, and EGFR inhibitor gefitinib and Syk inhibitor can block Blimp-1 gene expression caused by PMA. Reporter assay of Blimp-1 promoter activity further indicated the involvement of AP-1 in PMA-, TNF-α-, LPS- and EGF-elicited Blimp-1 mRNA expression. Confocal microscopic data indicated the nuclear loclization of Blimp-1, and such localization was not changed by stimuli. Moreover, Blimp-1 silencing enhanced SCC cell migration. Taken together, Blimp-1 can be transcriptionally upregulated by several stimuli in keratinocytes and SCC via EGFR transactivation and AP-1 pathway. These include growth factor PMA, cytokine TNF-α, TLR ligands (LPS and polyIC), and ROS insults (H2O2 and UVB). The function of Blimp-1 as a negative regulator of cell migration in SCC can provide a new therapeutic target in SCC.

Association of rosacea with depression and anxiety: A systematic review and meta-analysis.

BACKGROUND: Rosacea is associated with several comorbidities, but its relationship with psychiatric disorders remains controversial. We aimed to investigate the association of rosacea with depression and anxiety. METHODS: A systematic review was performed of relevant observational studies in the PubMed, Web of Science, Embase, and Wanfang databases from inception to June 8, 2021. The inclusion criteria for eligible studies were observational studies comparing the incidence or prevalence of depression or anxiety between patients with rosacea and individuals without rosacea. We conducted meta-analyses with a random-effects model. The main outcome was pooled analysis of prevalence or incidence of depression and anxiety in patients with rosacea. RESULTS: We included nine studies with 101,114,209 patients with rosacea. A pooled analysis from cross-sectional and case-control studies revealed that patients with rosacea were significantly more likely to have depression (crude odds ratio [OR], 2.855; 95% confidence interval [CI], 1.258-6.481) and anxiety (crude OR, 2.373; 95% CI, 1.448-3.888) than matched controls; however, adjusted ORs showed no significant association. Furthermore, the meta-analysis from cohort studies indicated that patients with rosacea have significantly higher risks of developing depression (adjusted incidence rate ratio [IRR], 2.443; 95% CI, 1.603-3.723) and anxiety (adjusted IRR, 2.181; 95% CI, 1.660-2.864). LIMITATIONS: Data for a subgroup analysis based on different demographic factors were insufficient. CONCLUSIONS: Current findings provide more evidence that rosacea is significantly associated with depression and anxiety, and rosacea may predispose patients to develop depression and anxiety. Clinicians should be aware of the psychological aspects of rosacea.

Effects of anti-inflammatory treatment on efficacy of selective laser trabeculoplasty: a systematic review and meta-analysis.

BACKGROUND: Selective laser trabeculoplasty (SLT) can evidently reduce intraocular pressure (IOP) in cases of open-angle glaucoma. Several studies have investigated the effectiveness of anti-inflammatory treatment to relieve discomfort after SLT, but whether such treatments affect the response of SLT remains uncertain. METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library for relevant studies published before 31 March 2021. The major outcomes were the efficacy of post-SLT anti-inflammatory treatment on IOP reduction, incidence of discomfort, and anterior chamber inflammation compared with those of placebo agents. RESULTS: Five randomized controlled trials with 235 eyes receiving anti-inflammatory treatment and 170 eyes receiving placebo agents were included in the meta-analysis. Compared with placebo, no significant differences were present in IOP reduction effects upon using topical non-steroidal anti-inflammatory drugs or steroid post-SLT. The results were consistent from 1 to 6 months during follow-up. Furthermore, anti-inflammatory treatment had no significant effects on pain or discomfort or the presence of anterior chamber cells 1 h to 1 week post-SLT. CONCLUSION: Topical anti-inflammatory treatment after SLT for patients with glaucoma neither significantly affected IOP reduction nor remarkably relieved clinical discomfort and anterior chamber inflammation. Hence, regular use of post-SLT anti-inflammatory treatment may be unnecessary.