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Behcet's disease, which is characterised by oral and genital ulcerations and eye inflammation, was discovered by Hulusi Behcet in 1937. Other features include arthritis, thrombophlebitis, neurological abnormalities, and skin lesions. Increased incidence of vascular manifestations has been reported in patients with Behcet's disease and may constitute one of the most important causes of mortality and morbidity in those patients.1 The disease is characterised by a relapsing inflammatory process of unknown aetiology.
Lipoprotein (a) (Lp(a)) is a cholesterol rich plasma lipoprotein that has emerged as an important risk factor for development of coronary artery disease and stroke. Lp(a) could contribute to lipid deposition on arterial walls. Moreover, the recent finding that apo(a) is analogous to plasminogen suggests the possibility that Lp(a) could be the link between thrombosis and atherosclerosis.2 3
The aim of this study was to measure the plasma concentrations of Lp(a) in patients with Behcet's disease and to find relationships between Lp(a) concentrations and clinical findings including disease activity, ocular involvement, articular symptoms, skin lesions, neurologic involvement, and other lipid parameters.
The study group included 27 patients with Behcet's disease (15 men and 12 women; mean (SD) age 33.1 (10) years, range 19–65 years) and 17 healthy control subjects (10 men and 7 women; mean age 33.5 (12.1) years, range 18–59 years). The groups were matched for factors influencing lipoprotein concentrations such as diet, body mass, and exercise.
Oral aphthous lesions were found in all the patients with Behcet's disease. Ocular involvement was seen in 14 patients, genital ulcerations in 14 patients, and skin lesions (erythema nodosum, pyoderma, folliculitis, skin ulcers, etc) in 12 patients. Arthritis or arthritis-like joint involvement occurred in 12 patients, and neurologic involvement in three patients. At the time of the study, the patients were being treated with either colchicine (n = 5) or non-steroid anti-inflammatory drugs (n = 10), or both (n = 8), the remaining four patients receiving no systemic medication.
Serum total cholesterol was measured by a cholesterol oxidase enzymatic method, triglycerides by a glycerol oxidase enzymatic method, and high density lipoprotein cholesterol (HDL-C) by a cholesterol oxidase enzymatic method in supernatant after precipitation with phosphotungstic acid–magnesium chloride. Apolipoproteins AI and B were determined by an immunoassay method (Sera-Pak Immuno Apo AI (code no. 6821)/Apo B (code no. 6822), Ames, Canada). Low density lipoprotein cholesterol (LDL-C) was calculated by the Friedewald formula. Lp(a) was measured using commercial anti-apo(a) polyclonal capture enzyme linked immunosorbent assay (TintElize Lp(a), catalogue no. 610210; Biopool AB, Umea, Sweden) according to the instructions of the manufacturer; an intra-assay coefficient of variation of 6.1% was obtained at the 31 mg/dl concentration of Lp(a) reference plasma (Biopool, catalogue no. 610142, n = 10).
Data were expressed as mean (SD). Lp(a) concentrations and other lipid parameters were compared by Mann Whitney U test, because of the skewed distributions of these values. Disease duration of the patients with Behcet's disease, cholesterol, triglyceride, LDL, HDL, Apo AI, and Apo B were compared with Lp(a) concentrations using regression analyses.
The results are summarised in table 1. Plasma Lp(a) concentrations in patients with Behcet's disease were significantly higher than in the healthy controls. There were no significant differences in the concentrations of total cholesterol, HDL-C, LDL-C, triglycerides, and apolipoproteins AI and B between patients and controls. As shown in table 1, plasma Lp(a) concentrations were not influenced by disease activity, but were affected by the presence of ocular, neurologic, and articular involvement, and skin lesions. Also, no correlation was observed between plasma Lp(a) concentrations and plasma concentrations of cholesterol, HDL-C, LDL-C, Apo AI, and Apo B, except for triglycerides (r = 0.66, p < 0.01).
Atherogenic, thrombogenic, and inflammatory vascular events increase in patients with Behcet's disease. High concentrations of Lp(a) (> 30 mg/dl) increase the risk of atherogenic and thrombogenic events.
Scott estimated that at plasma Lp(a) concentrations of 30 mg/dl, cellular plasminogen binding of Lp(a) is reduced 20%, thereby decreasing cell fibrinolysis and promoting a procoagulant state.4 Previously, Orem and colleagues from Turkey also reported that fluctuations of plasma Lp(a) concentrations with disease activity may be a contributing risk factor in the development of thrombogenic complications in patients with Behcet's disease.5 In addition, in the present study, significant relations were found between Lp(a) concentrations and neurologic, articular, and ocular involvements and skin manifestations within the study group. These findings may be related to vascular manifestations. Also, Lp (a) concentrations were correlated with triglyceride concentrations.
This study suggests that plasma Lp(a) concentrations increase in patients with Behcet's disease. Lp(a) may therefore play a role in the thrombogenic and atherosclerotic events associated with this disease.
Increased concentrations of LP(a) have been reported previously in Behcet's disease patients. Thrombosis, in various forms, is a recognised complication. The present report confirms raised plasma LP(a) concentration in Behcet's patients and suggests that ocular, cutaneous, articular, and neurological manifestations of the disease may be particularly associated with raised plasma LP(a). Whether LP(a) is causally related to the vasculitic nature of the disease is unknown, but it is hypothesised that an atherosclerotic/thrombotic mechanism may be involved in the syndrome.