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Plasma homocysteine was assessed in Behçet's disease (BD) patients in order to determine the prevalence of hyperhomocysteinaemia in BD and to test its association with clinical manifestations of the disease. The study included 59 patients with BD and 118 age-and sex-matched healthy subjects. Plasma homocysteine, vitamin B12 and folate were assessed by automated immunoassay methods. Hyperhomocysteinaemia was defined as plasma homocysteine > 15 μmol/l. Plasma homocysteine concentrations and the prevalence of hyperhomocysteinaemia were significantly higher in BD patients than in controls [median (5th–95th percentile), 11.3 (6.6–28.1) vs. 10.6 (6.6–17.1) μmol/l, and 25.4% vs. 9.3%, respectively]. In BD patients, hyperhomocysteinaemia was related to male gender, disease severity and uveitis [odds ratio (OR), 5.32; 95% confidence interval (CI), 1.43–21.61; p = 0.008], but not to age, smoking, disease activity, deep venous thrombosis, arthritis or neurological involvement. The association between uveitis and hyperhomocysteinaemia persisted (multi-adjusted OR, 7.46; 95% CI, 1.03–54.3; p = 0.05) after adjusting for gender, age, disease activity and duration, smoking, deep venous thrombosis, and serum concentrations of creatinine, vitamin B12 and folate. Plasma homocysteine should be measured in patients with BD, and the effect of B-vitamin supplementation should be tested in those with hyperhomocysteinaemia.