Thrombosis In Behcet's Disease Research Articles

Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential biomarkers in Behçet's disease: ameta-analysis.

The mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have attracted interest as possible indicators of inflammation and disease activity in various diseases. This meta-analysis assessed the association between NLR, MPV, PLR, and Behçet's disease (BD) and their correlation with disease activity and thrombosis. Athorough search of the Medline, Embase, and Cochrane databases was performed to identify relevant studies. Studies comparing NLR, MPV, and PLR between patients with BD and healthy controls, as well as studies examining these measures in connection with disease activity and thrombosis in BD satisfied the inclusion criteria. The standardized mean difference (SMD) and 95% confidence interval (CI) were used to calculate the effect sizes. This meta-analysis included 24articles. The findings revealed no discernible differences in MPV between the BD and control groups (p = 0.992). NLR was substantially higher in the BD group than in the control group (p < 0.001). PLR was higher in the BD group than in the control group (p = 0.030), indicating that BD is associated with alarger PLR. Patients with active and inactive BD did not vary significantly in terms of disease activity according to the MPV. Comparing MPV between patients with BD with and without thrombosis showed no discernible changes. However, individuals with active BD had aconsiderably higher NLR and PLR than those with inactive BD (p = 0.003 and p = 0.005, respectively). The statistical significance threshold for the association between NLR, PLR, and thrombosis in patients with BD was not met. NLR and PLR can be regarded as general markers of inflammation according to the results of this meta-analysis.

Intracranial Hypertension in Behcet Disease: A Case Report

Behcet disease (BD) is a chronic multisystem disorder characterized predominantly by recurrent episodes of occlusive vasculitis. According to the accumulated data, it is seen that intracranial hypertension generally develops secondary to the cerebral venous sinus thrombosis in BD. In the study, it was aimed in light of literature to discuss a case where intracranial hypertension occurred without venous sinus thrombosis. A 36-year-old female was evaluated for the symptoms of blurred vision in her left eye for the last 3 months and transient visual obscurations in her right eye beginning 3 days ago. It was found out that the patient had been diagnosed with BD one and a half months ago. Fundus examination revealed bilateral swollen optic discs. Lumbar puncture revealed an opening pressure of 360 mm H2O, with normal composition. The patient was diagnosed with intracranial hypertension developing secondary to BD according to modified Dandy criteria. Methylprednisolone 1000 mg intravenously (IV) for 5 days, followed by prednisolone 60 mg po, was administered. A significant improvement was observed in the complaints and papilledema of the patient. Inflammation could play a significant role in the intracranial hypertension developing without venous sinus thrombosis in BD. As a result, BD should be considered in the differential diagnosis in patients with intracranial hypertension especially in areas where the disease prevalence is high.

Methotrexate Therapy in Deep Venous Thrombosis in Behcet Disease in Children

Behcet disease is a chronic condition, systemic disease, with etiopathology still incomplete known but in witch are involved immune and genetic factors who may lead to inflammation and coagulation conditions. Authors present the case of a patient, masculine sex, 14 years old, diagnosed with Behcet disease, who had the vascular manifestation, with deep and superficial lower extremity vein thrombosis, that appeared at more than five years after first signs of disease (recurrent oral ulcerations). The patient had not presented positive markers for primary thrombophilia. Methotrexate therapy led to complete disappearance of lower extremity vein thrombosis, after about one year of treatment (as shown in Doppler vascular ultrasound). No side effect was observed related to Methotrexate therapy. Conclusions: Methotrexate therapy may be a very efficient alternative treatment in deep lower extremity vein thrombosis in Behcet disease, without anticoagulants association.

Evaluation of asymptomatic venous disease by venous Doppler ultrasonography in patients with Behcet's disease without overt thrombosis

One of the major causes of mortality and morbidity in Behcet's disease (BD) is vascular involvement. Limited data suggest a high prevalence of venous insufficiency (VI) and some cases of asymptomatic thrombosis in BD. In this study, we aimed to investigate asymptomatic venous disease by venous Doppler ultrasonography (US) prospectively in patients with BD, without known vascular disease. The study included 93 patients with BD (M/F, 45/48; age, 36.4 ± 10 years), 97 patients with ankylosing spondylitis (AS) (M/F, 50/47; age, 37.5 ± 9.5 years), and 43 healthy controls (HC) (M/F, 25/18; age, 34.7 ± 4.5 years). All patients were examined for the clinical findings of venous thrombosis. Vessels of both upper and lower extremities were examined, while the subjects were in supine position by venous Doppler US. Clinical signs ("C"), the various etiologies ("E"), anatomical sites ("A"), and pathophysiological disorder ("P") (CEAP) severity score was used to evaluate the severity of the VI. We did not detect any "silent thrombosis" in any group. VI findings in lower extremity were detected in 32.2 % (n = 30) in the BD group, 28.8 % (n = 28) in AS group, and 9.3 % (n = 4) in the HC group. Both BD and AS patients had significantly higher VI rates than controls (p = 0.007 and 0.015). Similarly, CEAP severity score in BD (0.34 (0-3)) was significantly higher than controls (0, p = 0.008) but similar to AS (0.18 (0-39), p = 0.18). No correlations were present between C-reactive protein elevation (>5 mg/L) and VI in both BD (p = 0.546) and AS (p = 0.754). A high prevalence of VI was present in both BD and AS patients without symptomatic thrombosis. Presence of VI also in AS, a disease without a major tendency to venous thrombosis, might suggest that chronic inflammation might cause a mild insufficiency detected only by Power US in venous vessels. Long-term consequences of this finding require further follow-up studies to show whether asymptomatic venous disease is a predictor of future venous thrombotic events in patients with BD.

Behçet’s Disease

Neurologic involvement in Behçet's disease (BD) is seen in about 5% to 10% of all BD patients. Clinical and imaging data suggest that neurologic involvement in BD presents in two major forms. The first, central nervous system (CNS) parenchymal involvement with a predilection to brainstem-diencephalic regions, is seen in the majority of patients with neuro-BD (NBD). The second form is cerebral venous sinus thrombosis (CVST), which is seen in up to 20% of cases. BD is very rare in children, but when it does occur, the patterns are reversed: most children with NBD present with CVST. Other syndromes such as spinal cord involvement, arterial CNS involvement, optic neuritis, aseptic meningitis, and peripheral neuropathies may be seen, but are rare. Venous sinus thrombosis in BD has a significantly better neurologic prognosis than parenchymal CNS involvement. There is no Class I evidence regarding treatment of parenchymal CNS involvement or CVST in BD. Current treatment applications are based largely on expert opinion; none are evidence-based. Acute parenchymal CNS involvement should be treated with high-dose intravenous methylprednisolone (IVMP), 1g per day, for 5 to 10days, followed by either a prolonged oral taper or intermittent IVMP pulses with a low oral dose between the pulses, over 6months. After treatment of the acute attack, long-term maintenance with immunosuppressive agents should be considered in patients with parenchymal CNS involvement, as this form may follow a relapsing or secondary progressive course and may result in significant physical and cognitive deficits leading to severe neurologic disability. A number of randomized controlled studies have tested treatments for systemic manifestations of BD. Colchicine was found to be effective for mucocutaneous symptoms, thalidomide was found to be effective in erythema nodosum-like skin lesions, azathioprine and cyclosporine were shown to be effective in BD uveitis, and cyclophosphamide was shown to be effective for major vascular involvement. More recently, interferon alfa and anti-TNF agents were also shown to be effective in BD uveitis. Although randomized controlled studies have not been performed in NBD, the most widely used long-term therapeutic agent is azathioprine. Recent observations suggest that the addition and long-term use of azathioprine in NBD could be associated with a more favorable course. A growing number of case reports in recent years suggest that anti-TNF agents may be an effective alternative in NBD, but current experience with these agents is limited. CVST in BD is also treated with steroids. The addition to glucocorticoids of anticoagulation, including short-term fractionated heparin, is controversial, as these patients have a higher probability of harboring pulmonary or other aneurysms, which may be associated with an increased risk of bleeding. Long-term oral anticoagulation is unnecessary. Interestingly, the prognosis of CVST due to BD seems to be much more favorable than the prognosis of CVST due to other causes, with much less tendency for venous infarcts and seizures. However, as recurrences may occur, long-term treatment with azathioprine is recommended.

CT angiographic demonstration of hepatic collateral pathways due to superior vena cava obstruction in Behçet's Disease

Behçet disease (BD) is a chronic multisystemic inflammatory disorder, mainly characterized by recurrent oral and genital ulcers, skin lesions, and uveitis. Large vein thrombosis in BD is unusual; when present, it is most frequently seen in the inferior or superior vena cava (SVC). The authors describe an unusual hepatic pseudolesion caused by abnormal focal enhancement through collateral pathways to the liver in two BD patients with SVC occlusion on three-dimensional multi-detector computed tomography, using volume rendering and maximum intensity projection techniques. BD should be suspected in patients presenting a focal increased hepatic enhancement area with collaterals caused by occlusion of the SVC without evidence of a hypercoagulable state or malignant mediastinal or thoracic venous inlet obstruction.

Chylothorax and chylopericardium as the initial clinical manifestation of Behcet’s disease

Behcet's disease (BD) is a chronic relapsing systemic vasculitic disorder affecting the arteries, veins, and vessels of any size. Large vein thrombosis in BD is not commonly developed and most commonly observed in the veins in the lower extremities and inferior or superior vena cava. In this report, a 18-year-old male patient with large vein thrombosis involving superior vena cava was presented. He was treated due to chylothorax and chylopericardium with SVC syndrome before diagnosis of BD. SVC thrombosis complicated by chylothorax and chyolpericardium can be a rare presenting initial symptom of BD.

Serum homocystein level and vascular thrombosis in patients with Behçet disease

AbstractObjective: Behçet disease (BD) is a multisystemic inflammatory disorder of unknown aetiology that in some patients will present with thrombosis. However, the mechanism of thrombosis is unknown. In this study, we investigate the correlation between homocystein level in BD patients with vascular thrombosis.Patient and methods: One hundred and twenty‐three patients who fullfilled the criteria of the International Study Group for BD (n = 77, 62.6% females and n = 46, 37.4% males) were included in this cross‐sectional study. Patients were divided into two groups: with thrombosis (n = 23, 18.7%) and without thrombosis (n = 100, 81.3%). All patients underwent colour Doppler sonography for documentation of vascular thrombosis. Serum homocystein was measured by ELISA method, folate and B12 were measured by radioimmunoassay.Results: Patients with vascular involvement, vein and/or arterial thrombosis were enrolled. Mean serum homocystein level was significantly higher in the group with thrombosis (P = 0.012) and in male patients than females (18.10 ± 5.5 vs. 13.21 ± 4.1). In multiple regression analysis, the only factors that persisted for thrombosis were age and sex (P = 0.02, P &lt; 0.0001, respectively). Serum folate and B12 were not correlated with thrombosis in BD.Conclusions: In this study, we found that mean homocystein levels were higher in BD patients with thrombosis and it may have a role in the process of thrombosis in BD.

Treatment of venous thrombosis associated with Behcet’s disease: immunosuppressive therapy alone versus immunosuppressive therapy plus anticoagulation

The aim of this study was to compare the efficacy of immunosuppressive therapy alone with that of combination therapy involving immunosuppressants and anticoagulation for the treatment of venous thrombosis in Behcet's disease (BD). A retrospective analysis was made of 37 patients with venous thrombosis in BD. BD patients with venous thrombosis were divided into three groups: one group (N = 16) received immunosuppressive therapy alone, another group (N = 17) received immunosuppressant and anticoagulation combination therapy, and the third group (N = 4) received anticoagulation therapy only. Clinical and laboratory parameters and the recurrence of venous thrombosis were assessed. Venous thrombosis in BD appeared to have a more diffuse pattern than idiopathic type and a predilection for lower limbs. The most commonly involved sites were the superficial and common femoral veins. Recurrence of venous thrombosis occurred in two cases in the immunosuppressant group (12.5%), one case in the combination therapy group (5.9%), and three cases in the anticoagulant group (75%). No significant difference was found between recurrence in the immunosuppressant and combination therapy groups. Acute phase reactants were elevated in all six patients at the time of venous thrombosis recurrence. Our study suggests that immunosuppressive therapy is essential and that anticoagulation therapy might not be required for the treatment of deep venous thrombosis associated with BD.

Methylenetetrahydrofolate reductase gene C677T mutation and plasma homocysteine level in Behçet's disease.

The aim of this study was to assess whether homozygosity for the 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation and plasma homocysteine concentration are related to deep vein thrombosis in Behçet's disease (BD) patients. Forty BD patients (23 males, 17 females; mean age 40.2+/-8.4 years) and 60 healthy controls (HC) (34 males, 26 females; mean age 41.6+/-6.9 years) were included in the study. Fourteen of the BD patients had a history of deep venous thrombosis (DVT), as confirmed by Doppler ultrasound. The rates of homozygosity for the MTHFR C677T mutation in the BD and HC groups were 7.5% and 10%, respectively. The distribution of MTHFR genotypes was similar in the two groups ( p>0.05), and analysis showed that homozygosity for the mutation was not a risk factor for DVT. The mean plasma homocysteine levels were 13.4+/-4.2 micro mol/l for the overall BD patients and 12.6+/-3.8 micromol/l for HC ( p>0.05). However, the mean plasma homocysteine level in the BD patients with DVT history (15.9+/-4.6 micromol/l) was significantly higher than the level in the BD patients with no DVT history (12.1+/-3.3 micromol/l) ( p=0.013) and the level in the HC group (12.6+/-3.8 micromol/l) ( p=0.025). The study results suggest that elevated plasma homocysteine level may play a role in the pathogenesis of venous thrombosis in BD.

Hemostatic parameters in Behçet's disease: a reappraisal.

Behçet's disease (BD) is a relapsing vasculitis in which orogenital ulceration is a prominent feature. The disease presents a tendency to thrombosis. The prevalence of venous or arterial thrombosis in BD reaches 40% in some series. Molecular markers of imbalance have been extensively studied in BD. The aim of this paper is to review current data on essential hemostatic parameters. The precise pathogenetic mechanism(s) underlying the prothrombotic state of BD is unknown. Thrombophilic factors could contribute to thrombosis in BD. Vasculitic endothelial injury may trigger or enhance the pathological hemostatic process.

Hyperhomocysteinaemia in Behçet's disease.

Arterial and venous thrombosis are among the clinical features of Behçet's disease (BD), the pathogenesis of which is not completely understood. In this study, we investigated whether hyperhomocysteinaemia, being a well known risk factor for thrombosis, is also a contributive risk factor for the arterial and venous thrombosis of BD. Eighty-four patients fulfilling the criteria of the International Study Group for Behçet's Disease (54 males, 30 females, mean age 36+/-9 yr) were enrolled. All the patients were carefully screened for a history of venous thrombosis and were separated into two groups with respect to thrombosis history. Thirty-six healthy individuals (23 males, 13 females), matched for age and sex with the BD group, were included as a negative control group. Patients were excluded if they had any condition that might affect plasma homocysteine concentration. As methotrexate (MTX) causes hyperhomocysteinaemia, we also included 29 rheumatoid arthritis patients (five males, 24 females) receiving MTX weekly. Fasting plasma homocysteine concentrations were measured by high-performance liquid chromatography. The data were analysed with the chi(2) test and Student's t-test. The highest homocysteine concentrations were found in the MTX group (17.5+/-5.3 micromol/l). Mean plasma homocysteine concentrations in BD patients were significantly higher than in the healthy controls (11.5+/-5.3 vs. 8.8+/-3.1 micromol/l, P<0.001). Among BD patients with a history of thrombosis, 20 of 31 (64%) had hyperhomocysteinaemia, and this was significantly higher than in those without thrombosis (9%). On the other hand, there was no significant difference between patients with non-thrombotic BD and healthy controls (P>0.05). In patients with thrombosis, we found no correlation between the duration of the post-thrombotic period and homocysteine concentration. Among all the variables investigated, only hyperhomocysteinaemia was found to be related to thrombosis. Hyperhomocysteinaemia may be assumed to be an independent risk factor for venous thrombosis in BD. Unlike the factor V Leiden mutation, hyperhomocysteinaemia is a correctable risk factor. This finding might lead to new avenues in the prophylaxis of thrombosis in BD.

Thrombosis in Behçet's disease: a retrospective survey from a single UK centre.

To contribute to knowledge of vascular occlusion in Behçet's disease (BD), prevalence and relative risk for thrombosis were ascertained retrospectively in a cohort of Caucasian patients with the disease. The study included 73 BD patients (36 males, 37 females, mean age 45+/-11 yr) attending the Immunology/Rheumatology Department of Northwick Park Hospital. A group of 146 patients without BD, attending the same department, served as a control group. Thrombosis was more frequent in BD patients than in controls (23/73, 32% vs 7/146, 5%, P<0.001). This was accounted for by a higher prevalence of venous thrombosis in BD patients (18/73, 25% vs 4/146, 3%, P<0.001). Gender-adjusted data revealed an 11-fold risk of developing any thrombosis and a 14-fold risk of developing venous thrombosis in BD. After adjusting for differences in age at first symptoms, male BD patients showed a 6-fold higher risk of vein thrombosis. Males reported more often thrombophlebitis (13/36, 36% vs 0/0, P<0.001), folliculitis (8/36, 22% vs 1/37, 3%, P<0.01) and retinal vasculitis (13/36, 36%, vs 4/37, 11%, P=0.01) than females, in whom arthralgia prevailed (23/37, 62%, vs 12/36, 33%, P=0.01). In our population, BD confers a 14-fold risk of developing venous thrombosis. The risk is sixfold higher in male BD patients, who fare worse than females with regard to thrombophlebitis, folliculitis and retinal vasculitis.

Behçet's Disease.

Clinical and imaging data suggest that Behçet's disease (BD) can present with a variety of neurologic complications, which may be subclassified into two forms. One is attributable to small venous inflammatory disease with focal or multifocal central nervous system involvement and is seen in the majority of patients. It is designated Central Nervous System-Neuro-Behçet syndrome (CNS-NBS). The other form is due to cerebral venous sinus thrombosis and has limited symptoms and a better prognosis. It is very uncommon for these two types of involvement to occur in the same individual. It is very likely that the two major forms have different pathogeneses. Patients with small vein inflammation should be considered for aggressive treatment. A substantial number of patients in this group will have a relapsing-remitting course; for some, this will evolve into a secondary progressive course. A few patients from this group will have progressive CNS dysfunction from the onset. Acute attacks of CNS-NBS are treated with either oral prednisone (1 mg/kg/d up to 4 weeks or until improvement is observed) or high-dose intravenous methylprednisolone (IVMP), 1 g/d for 5 to 7 days. After either treatment, an oral tapering dose of glucocorticoids should be given over 2 to 3 months to avoid early relapses. Some patients may require the long-term use of low maintenance doses of glucocorticoids to prevent exacerbations. Immunosuppressive agents (eg, azathioprine, cyclosporine A, cyclophosphamide, and chlorambucil), given either alone or in different combinations (eg, azathioprine with cyclosporine) for the long-term treatment of various systemic manifestations of BD, have not been shown to prevent the development of the neurologic complications of the disease, reduce its exacerbations, or stop its progression. Immunomodulatory treatments such as interferon alfa and thalidomide have been shown to be effective in treating some of the systemic manifestations of BD, but there is no information on their effects on the development and progression of CNS-NBS. Cerebral venous sinus thrombosis in BD is treated with either intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin given together with a short course of glucocorticoids. Evidence of benefit from this treatment, however, is weak.

Coagulation factor V gene mutation increases the risk of venous thrombosis in behçet's disease.

We investigated the prevalence of the coagulation factor V gene G1691A mutation in 64 patients with Behçet's disease (BD) and in 107 apparently healthy individuals. The mutation was present in the heterozygous state in 37.5% of the patients with a history of deep vein thrombosis (12/32) and in 9.4% of the patients without any thrombotic event (3/32). Eleven healthy individuals were also heterozygous for the mutation (10.3%). The prevalence of the mutation in BD patients with and without thrombosis was significantly different (P = 0.0079). We conclude that the factor V gene mutation may play a major role in the development of venous thrombosis in BD.