Plasma Homocysteine in Behcet's Disease: A Systematic Review and Meta-Analysis

Aim To evaluate the relevance of plasma homocysteine (HC) in Behcet's disease (BD) and its clinical manifestations. Methods Systematic review of EMBASE and PubMed databases according to PRISMA guidelines from inception to July 2021; random-effects meta-analyses for continuous outcomes. Results The search strategy retrieved 48 case-control (2,669 BD and 2,245 control participants) and 5 cohort studies (708 BD participants). Plasma HC was higher in BD than in controls (p < 0.0001) with wide heterogeneity (I ²= 89.7%) that remained unchanged after sensitivity analysis according to year of article publication, age of BD participants, study size, study quality, method of HC determination, and male/female ratio >1.5; some pooled ethnicities explained a small part of the heterogeneity (I ²= 16.3%). Active BD participants had higher HC than inactive ones (p < 0.0001), with moderate heterogeneity (I ²= 49.2%) that disappeared after removal of an outlier study with very high disease activity. BD participants with any vascular involvement had higher HC than those without (p < 0.0001) with wide heterogeneity (I ²= 89.7%); subgroup analysis on venous thrombosis only changed neither effect size (p < 0.0001) nor heterogeneity (I ²= 72.7%). BD participants with ocular involvement had higher HC than those without (p < 0.0001) with moderate heterogeneity (I ²= 40.3%). Conclusion Although causality cannot be inferred, the consistency of the elevation of plasma HC in BD, particularly in patients with active disease, with vascular and ocular involvement suggests an intrinsic involvement of HC in these clinical manifestations.