Pharmacogenomics on the Treatment Response in Patients with Psoriasis: An Updated Review.

The efficacy and the safety of psoriasis medications have been proved in trials, but unideal responses and side effects are noted in clinical practice. Genetic predisposition is known to contribute to the pathogenesis of psoriasis. Hence, pharmacogenomics gives the hint of predictive treatment response individually. This review highlights the current pharmacogenetic and pharmacogenomic studies of medical therapy in psoriasis. HLA-Cw*06 status remains the most promising predictive treatment response in certain drugs. Numerous genetic variants (such as ABC transporter, DNMT3b, MTHFR, ANKLE1, IL-12B, IL-23R, MALT1, CDKAL1, IL17RA, IL1B, LY96, TLR2, etc.) are also found to be associated with treatment response for methotrexate, cyclosporin, acitretin, anti-TNF, anti-IL-12/23, anti-IL-17, anti-PDE4 agents, and topical therapy. Due to the high throughput sequencing technologies and the dramatic increase in sequencing cost, pharmacogenomic tests prior to treatment by whole exome sequencing or whole genome sequencing may be applied in clinical in the future. Further investigations are necessary to manifest potential genetic markers for psoriasis treatments.

New Onset and Exacerbation of Autoimmune Bullous Dermatosis Following COVID-19 Vaccination: A Systematic Review.

BACKGROUND: Cases of autoimmune bullous dermatosis (AIBD) have been reported following COVID-19 vaccination. OBJECTIVE: We aimed to provide an overview of clinical characteristics, treatments, and outcomes of AIBDs following COVID-19 vaccination. METHODS: We conducted a systematic review and searched the Embase, Cochrane Library, and Medline databases from their inception to 27 March 2024. We included all studies reporting ≥ 1 patient who developed new-onset AIBD or experienced flare of AIBD following at least one dose of any COVID-19 vaccine. RESULTS: We included 98 studies with 229 patients in the new-onset group and 216 in the flare group. Among the new-onset cases, bullous pemphigoid (BP) was the most frequently reported subtype. Notably, mRNA vaccines were commonly associated with the development of AIBD. Regarding the flare group, pemphigus was the most frequently reported subtype, with the mRNA vaccines being the predominant vaccine type. The onset of AIBD ranged from 1 to 123 days post-vaccination, with most patients displaying favorable outcomes and showing improvement or resolution from 1 week to 8 months after treatment initiation. CONCLUSIONS: Both new-onset AIBD and exacerbation of pre-existing AIBD may occur following COVID-19 vaccination. Healthcare practitioners should be alert, and post-vaccination monitoring may be essential.

Association between Dupilumab and Conjunctivitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Conjunctivitis is commonly reported in dupilumab users with atopic dermatitis (AD), and few studies have compared the risk of conjunctivitis among patients with different indications. This study aimed to investigate the association between dupilumab and conjunctivitis in various diseases. The protocol of this study was registered on PROSPERO (ID CRD42023396204). The electronic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov was conducted for the period from their inception to January 2023. Only placebo-controlled, randomized controlled trials (RCTs) were included. The main outcome was the incidence of conjunctivitis during the study period. The subgroup analysis was performed for patients with AD and non-AD indications, which include asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. In total, 23 RCTs involving 9153 patients were included for meta-analysis. Dupilumab users exhibited significantly higher risk of conjunctivitis (risk ratio [RR], 1.89; 95% confidence interval [CI], 1.34-2.67) than placebo users. Notably, significantly increased incidence of conjunctivitis was observed in the dupilumab group relative to the placebo group among patients with AD (RR, 2.43; 95% CI, 1.84-3.12) but not among patients with non-AD indications (RR, 0.71; 95% CI, 0.43-1.13). In conclusion, only dupilumab users with AD but not those with non-AD indications reported an elevated incidence of conjunctivitis.

cT1N0M0 Esophageal Squamous Cell Carcinoma Invades the Muscularis Mucosa or Submucosa: Comparison of the Results of Endoscopic Submucosal Dissection and Esophagectomy.

BACKGROUND: Endoscopic submucosal dissection (ESD) combined with selective adjuvant chemoradiotherapy may be a new treatment option for cT1N0M0 esophageal squamous cell carcinoma (ESCC) invading muscularis mucosa or submucosa (pT1a-M3/pT1b). We aim to report the effectiveness of this treatment by comparing the results of esophagectomy. METHODS: This retrospective single-center study included 72 patients with pT1a-M3/pT1b ESCC who received ESD combined with selective adjuvant chemoradiotherapy (n = 40) and esophagectomy (n = 32). The main outcome comparison was overall survival (OS). The secondary outcomes were treatment-related events, including operation time, complication rate, and length of hospital stay. Disease-specific survival (DSS) and progression-free survival (PFS) were also evaluated. RESULTS: There were no significant differences in the rates of OS, DSS, and PFS between the two groups (median follow-up time: 49.2 months vs. 50.9 months); these were also the same in the subgroup analysis of pT1b ESCC patients. In the ESD group, the procedure time, overall complication rates, and length of hospital stay were significantly reduced. However, the metachronous recurrence rate was significantly higher. In a multivariate analysis, tumor depth and R0 resection were the independent factors associated with OS. CONCLUSIONS: ESD combined with selective adjuvant chemoradiotherapy can be an alternative treatment to esophagectomy for cT1N0M0 ESCC invading muscularis mucosa or submucosa.

Psoriasis Patients with Specific HLA-Cw Alleles and Lower Plasma IL-17 Level Show Improved Response to Topical Lindioil Treatment.

Purpose: Lindioil, a medicine refined from indigo naturalis (a herb used in Chinese medicine), is effective in treating severe psoriasis; however, responses vary across individual patients. We aim to investigate genetic predispositions associated with treatment response to topical Lindioil among patients with psoriasis and correlations with plasma cytokine patterns. Patients and Methods: We enrolled 72 psoriasis patients treated with Lindioil ointment and analyzed the human leukocyte antigen class C (HLA-Cw) genotypes and plasma cytokine expression patterns. We developed regression models of treatment response, defined as Psoriasis Area and Severity Index (PASI) 75, to examine correlations among HLA-Cw alleles, cytokine levels, and treatment response to Lindioil. Results: Patients harboring HLA-Cw*06:02 were significantly more likely to respond to Lindioil (P = 0.02, odds ratio [OR]: 6.88), whereas Lindoil was ineffective in those harboring HLA-Cw*01:02 (P = 0.01, OR: 0.28). Patients who were HLA-Cw*06:02-positive or HLA-Cw*01:02-negative had better PASI scores and body surface area (BSA) improvement (73.3% vs 44.4%, P<0.001) following an 8-week treatment period. Psoriasis patients achieving PASI 75 after 8 weeks presented with lower baseline plasma interleukin-17 (IL-17) levels than those who did not achieve PASI 75 (PASI 75: 11.28 pg/mL vs PASI <75: 15.82 pg/mL, P = 0.05). Conclusion: Our findings suggest that the presence of the HLA-Cw*06:02 or HLA-Cw*01:02 alleles and plasma IL-17 levels are predictive markers of treatment response to Lindioil ointment in patients with psoriasis.