Homocysteine: An activity marker in Behçet's disease?
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
References (41)
- et al.
Pathologic features of Behçet's syndrom: a review of Japanese autopsy registry data
Hum Pathol
(1985) - et al.
Plasma homocysteine concentrations and risk of coronary artery disease in UK Indian Asian and European men
Lancet
(2000) - et al.
Evidence that homocysteine is an independent risk factor for atherosclerosis in hyperlipidemic patients
Am J Cardiol
(1995) Hyperhomocysteinemia: a risk factor for central retinal vein occlusin
Am J Ophtalmol
(2000)- et al.
Vascular endothelial function and oxidative stress mechanisms in patients with Behçet's syndrome
J Am Coll Cardiol
(2001) - et al.
Behçets disease and complex aphthosis
J Am Acad Dermatol
(1999) - et al.
Homocysteine and vascular disease
Lancet
(1999) - et al.
Hyperhomocysteinaemia in retinal artery and retinal vein occlusion
Am J Ophthalmol
(1993) - et al.
Factor V Leiden mutation is associated with ocular involvement in Behçet's disease
Am J Opthalmol
(1999) - et al.
Homocysteine and thrombotic disease
Blood
(1997)
Uber residivierende aphthose, durch ein virus verursachte geschwure am mund, am auge und an den genitalien
Dermatol Wochenschr
Inaba G: Behçet's disease
N Engl J Med
Plasma von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, and antithrombin III levels in Behçet's disease
Scand J Rheumatol
Coagulation and fibrinolytic activity in Behçet's disease
Thromb Haemost
Overproduction of monocyte derived tumor necrosis factor alpha interleukin (IL) 6, IL-8 and increased neutrophil superoxide generation in Behçet's disease: a comparative study with familial Mediterranean fever and healthy subjects
J Rheumatol
Auto-oxidative damage in Behçet's disease endothelial cell damage following the elevated oxygen radicals generated by stimulated neutrophils
Clin Exp Immunol
Oxidative stress in Adamantiades-Behçet's disease
Dermatology
Lipid peroxidation and antioxidant defence system in patients with active or inactive Behçet's disease
Acta Derm Venerol
A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians
JAMA
Plasma homocysteine as a risk factor for vascular disease: the European Concerted Action Project
JAMA
Cited by (40)
Hematinic deficiencies and hyperhomocysteinemia in gastric parietal cell antibody-positive or gastric and thyroid autoantibodies-negative Behcet's disease patients
2019, Journal of the Formosan Medical AssociationCitation Excerpt :Moreover, we also demonstrated that 30.2%, 34.9%, 6.3%, 6.3%, and 14.3% of 63 BD patients have blood hemoglobin (Hb), iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia, respectively.4 Previous studies also found that active, thrombotic or ocular BD patients have a significantly higher mean serum homocysteine level and a significantly higher frequency of hyperhomocysteinemia than healthy control subjects and than inactive, non-thrombotic or non-ocular BD patients, respectively.5–13 Hyperhomocysteinemia can be attributed to deficiencies of vitamin B6, vitamin B12, and/or folic acid.14–18
Significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia in patients with Behcet's disease
2018, Journal of the Formosan Medical AssociationCitation Excerpt :These findings indicate that by strict WHO criteria the normocytic anemia and iron deficiency anemia are the two more common types of anemia in our 63 BD patients (see Table 3). BD is a chronic, multisystemic, and inflammatory disorder commonly complicated by vasculitis and vascular thrombosis.3–11 Homocysteine is an independent risk factor for venous and arterial thrombosis.5,11
Hemoglobin, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia in Behcet's disease patients with atrophic glossitis
2018, Journal of the Formosan Medical AssociationCitation Excerpt :The above-mentioned findings indicate that anemia and hematinic (especially, vitamin B12 and folic acid) deficiencies may be the important factor that cause AG,3,18 and in turn result in hyperhomocyteinemia in a portion of AG+/RAS and AG+RAS/BD patients.18 Moreover, the elevated serum homocysteine may subsequently cause active, thrombotic and/or ocular diseases in BD patients.4–12 Shadmanfar et al.45 found no significant differences in either the mean plasma homocysteine level or the prevalence of hyperhomocysteinemia between HLA-B51-positive BD patients and HLA-B51-negative BD patients or healthy control subjects.
Huge femoral artery pseudoaneurysm in a patient with Behçet's disease
2017, Egyptian RheumatologistBehçet's Disease
2016, Kelley and Firestein's Textbook of Rheumatology: Volumes 1-2, Tenth Edition