Homocysteine: An activity marker in Behçet's disease?

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Summary

Background

Behçet's disease (BD) is a chronic multisystem inflammatory disorder commonly complicated by vascular thrombosis.

Objective

In this study, we investigated whether hyperhomocysteinaemia, being a well known risk factor for atherothrombogenesis, is also a contributive risk factor for the pathogenesis and the activation of Behçet's disease.

Methods

Sixty-four patients fulfilling the criteria of the International Study Group for Behçet's disease (48 males, 16 females, 33 ± 8 years) were enrolled. They were separated into two groups with respect to activation features of Behçet's disease. Additionally, we collected the blood samples from 13 patients with BD in both active stage and in inactive stage. Twenty-six healthy individuals were included as a negative control group. Serum total homocysteine (Hcy) levels were determined by chemiluminescence immunoassay.

Results

Mean serum homocysteine concentrations in total BD patients were significantly higher than in the healthy controls (11.7 ± 4.6 versus 8.7 ± 2.8 μmol/L, p < 0.01). Mean serum homocysteine concentrations in the active patients were significantly higher than in the inactive patients and the healthy controls (13.3 ± 3.6; 10.8 ± 5.0; 8.7 ± 2.8 μmol/L, respectively) (p < 0.05 and p < 0.001, respectively). There was no significant difference between the patients with inactive disease and the healthy controls. When the active and the inactive stage of 13 patients with BD were compared, we found that mean serum total homocysteine levels were higher in the active stage than in the inactive stage (p < 0.05).

Conclusion

Hyperhomocysteinaemia may be responsible for the endothelial damage in BD and assumed to be a risk factor and a marker for activation of BD.

Introduction

Behçet's disease (BD) is a chronic, multisystem disorder characterized by recurrent oral and genital ulcerations, skin lesions and uveitis [1]. The cause of origin is yet unknown however, histopathologically predominant lesions are vasculitis, affecting both the vessel wall and perivascular tissues [2], and up to 25% of patients suffer systemic venous thrombosis [3]. Reports of elevated serum concentrations of von Willebrand factor, plasminogen activator inhibitor-1 and thrombomodulin suggest the presence of vascular endothelial dysfunction in patients with BD, though these abnormalities have not been consistently reported [4], [5]. On the other hand, evidence from recent studies suggests that activated leukocytes may contribute to vascular injury in BD [6], [7]. Concentration of circulating pro-oxidants and lipid peroxidation products are elevated in BD, however antioxidant system is deficient and inadequate, especially in patients who are in an active period of the disease [8], [9]. The relation between oxidative stress mechanisms and vascular injury in patients with BD has not yet been clarified.

Homocysteine (Hcy) is a sulphur-containing essential amino acid formed during the conversion of methionine to cysteine. Hyperhomocysteinaemia is a major and independent risk factor for vascular disease [10], [11], [12], [13], [14] and may occur in the course of diabetes mellitus, renal failure, hyperlipidaemia, psoriasis and inflammatory bowel disease [15], [16], [17], [18], [19].

Increasing evidences suggest that the vascular effects of homocysteine are mediated through an action on the endothelium. In healthy human subjects, elevated total Hcy (tHcy) concentrations are associated with impaired endothelium-dependent dilatation, an early manifestation of atherosclerosis [20], [21], [22], [23]. High levels of tHcy may cause lipid peroxidation, impaired vasomotor regulation, prothrombotic surface and therefore, vascular endothelial injury and atherothrombogenesis. The exact mechanisms linking homocysteine to endothelial disfunction are still unknown. Because hyperhomocysteinaemia may be prevented by supplementation with Vitamin B 12, Vitamin B 6 and/or folic acid, these parameters are potential methods of managing hyperhomocysteinaemia.

A limited number of studies conducted in recent years have shown that hyperhomocysteinaemia might be assumed to be an independent and correctable risk factor for venous thrombosis in BD [24]. Er et al. have reported that mean serum tHcy levels were higher in the patients with BD than in control subjects and were higher in active patients than those of inactive patients and control subjects [25]. They suggested that elevated tHcy might be responsible for the endothelial damage in BD and might be an additional risk factor for the development of retinal vascular occlusive disease.

The aim of this study was to investigate whether hyperhomocysteinaemia is a risk factor for the pathogenesis and the development of activation in BD.

Section snippets

Subjects

A total of 64 consecutive patients with BD (33 ± 8 years; range 17–58; 48 male and 16 female) attended our dermatology clinic and 26 age matched healthy control subjects (35 ± 8 years; range 20–54; 12 male and 14 female) were included in the present study. All BD patients fulfilled the criteria of the International Study Group for BD [26]. At the time of the clinical assessment, patients were included in the active group if they had at least two of the following clinical findings: oral ulcers,

Results

All patients with BD had oral aphthous stomatitis. Pathergy test was positive in 48 (75%). Articular symptoms were present in 45 patients (70%). Sixty-six percent of cases (n = 42) had genital ulceration and ocular involvement was found in 34 (53%). Skin lesions were present in 33 patients (52%). Five patients (8%) complained of neurological symptoms (Table 1). Demographic data of all groups are summarised in Table 2. The mean serum homocysteine concentrations in each study group are shown in

Discussion

The results showed that, in serum, the patients with active disease had markedly elevated tHcy levels compared to the patients with inactive disease or healthy controls. Serum tHcy levels were also significantly higher in whole BD patients than those in the healthy controls. However, there was no significant difference between the patients with inactive disease and control subjects.

The most prominent feature of BD is systemic vasculitis with endothelial dysfunction, affecting both vessel wall

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