Higher 25-hydroxyvitamin D level is associated with increased risk for Behçet's disease.

BACKGROUND & AIM: Previous studies showed a vitamin D deficiency in patients with Behçet's disease, suggesting potential benefits of vitamin D supplementation in the prevention and treatment of Behçet's disease. Interpretation of these studies may be limited by reverse causality or confounding bias. We aim to determine the causal association between serum 25-hydroxyvitamin D [25(OH)D] and the risk of Behçet's disease by Mendelian randomization. METHODS: An allele score formed by four variants (rs2282679, rs10741657, rs12785878 and rs6013897) that were associated with serum 25(OH)D level, was examined using data of genome-wide association study (GWAS) on 999 Behçet's disease and 4417 healthy individuals of Chinese ancestry and validated using data of GWAS on 1215 Behçet's disease and 1278 controls of Turkish ancestry. The primary outcome was the risk of Behçet's disease, evaluated by an inverse variance weighted average of the associations with genetically determined 25(OH)D levels. RESULTS: The inverse variance weighted estimate showed that genetically increased 25(OH)D level was associated with a higher risk of Behçet's disease. In the Chinese cohort, the odds ratio for Behçet's disease in one standard deviation increase of natural log-transformed 25(OH)D level was 3.82 (95% CI: 1.27-11.42). Data from Turkish cohort confirmed the association with Behçet's disease (OR, 95% CI: 4.18, 1.15-15.12). In overall combination of Chinese and Turkish cohorts, the odds ratio for Behçet's disease per standard deviation increase of natural log-transformed 25(OH)D level was estimated to be 3.96 (95% CI: 1.72-9.13; P = 0.001). No significant evidence of pleiotropy and heterogeneity was detected. CONCLUSIONS: On the basis of evidence in 7909 human beings, this study provides the newest indication that a lifelong higher 25(OH)D level is associated with an increased risk of Behçet's disease. Special attention should be paid to the potential harm of long-term or high-dose use of vitamin D supplements in clinical practice.

Significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia in patients with Behcet's disease.

BACKGROUND/PURPOSE: Behcet's disease (BD) patients may have one or more hematinic deficiencies. This study evaluated whether there were significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia in BD patients. METHODS: The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations in 63 BD patients were measured and compared with the corresponding levels in 126 age- and sex-matched healthy control subjects. RESULTS: We found that 30.2%, 34.9%, 6.3%, 6.3%, and 14.3% of 63 BD patients had hemoglobin, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia, respectively. Both 63 BD and 19 major-typed RAS/BD patients had significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than 126 healthy control subjects (all P-values < 0.05). Moreover, 44 minor-typed RAS/BD patients had significantly higher frequencies of hemoglobin and iron deficiencies than 126 healthy control subjects (both P-values < 0.001). Of the 19 anemic BD patients, one had pernicious anemia, one had macrocytic anemia, 12 had normocytic anemia, four had iron deficiency anemia, and one had thalassemia trait-induced anemia. CONCLUSION: There are significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia in BD patients. The normocytic anemia is the most common type of anemia in our 63 BD patients. We suggest that supplementations of vitamin BC capsules plus deficient vitamin B12 and/or folic acid may reduce the abnormally high serum homocysteine level to a relatively lower level in BD patients with hyperhomocysteinemia.

Overlooked Management and Risk Factors for Anemia in Patients with Intestinal Behçet's Disease in Actual Clinical Practice.

BACKGROUND/AIMS: Anemia in patients with inflammatory bowel disease significantly affects the quality of life. The aim of this study was to investigate the frequency of and risk factors for anemia and to describe the management of anemia in patients with intestinal Behçet's disease (BD) in actual clinical practice. METHODS: We included 64 patients with intestinal BD who visited the outpatient clinic of a tertiary referral center in June 2011 and had available laboratory data for the subsequent 6 months. RESULTS: Anemia was detected in 26 patients (40.6%). After 6 months, anemia was still present in 14 of these patients (53.8%). The cause of anemia was investigated in eight patients (30.8%), and oral iron supplementation was prescribed to four patients (15.4%). Of these four patients, two (50%) recovered completely within 6 months. Anemia was associated with a high Disease Activity Index for Intestinal Behçet's Disease (DAIBD, p=0.024), erythrocyte sedimentation rate (p=0.003), and C-reactive protein (p=0.049) in univariate analysis. In multivariate analysis, the factor predictive for anemia in patients with intestinal BD was a higher DAIBD (≥40; odds ratio, 4.08; 95% confidence interval, 1.21 to 13.71; p=0.023). CONCLUSIONS: Although anemia is common in intestinal BD patients, its clinical importance is overlooked in daily practice. Moderate to severe disease activity is predictive of anemia.

Overlooked Management and Risk Factors for Anemia in Patients with Intestinal Behcet's Disease in Actual Clinical Practice

BACKGROUND/AIMS: Anemia in patients with inflammatory bowel disease significantly affects the quality of life. The aim of this study was to investigate the frequency of and risk factors for anemia and to describe the management of anemia in patients with intestinal Behcet's disease (BD) in actual clinical practice. METHODS: We included 64 patients with intestinal BD who visited the outpatient clinic of a tertiary referral center in June 2011 and had available laboratory data for the subsequent 6 months. RESULTS: Anemia was detected in 26 patients (40.6%). After 6 months, anemia was still present in 14 of these patients (53.8%). The cause of anemia was investigated in eight patients (30.8%), and oral iron supplementation was prescribed to four patients (15.4%). Of these four patients, two (50%) recovered completely within 6 months. Anemia was associated with a high Disease Activity Index for Intestinal Behcet's Disease (DAIBD, p=0.024), erythrocyte sedimentation rate (p=0.003), and C-reactive protein (p=0.049) in univariate analysis. In multivariate analysis, the factor predictive for anemia in patients with intestinal BD was a higher DAIBD (> or =40; odds ratio, 4.08; 95% confidence interval, 1.21 to 13.71; p=0.023). CONCLUSIONS: Although anemia is common in intestinal BD patients, its clinical importance is overlooked in daily practice. Moderate to severe disease activity is predictive of anemia.

Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde-derived advanced glycation end-product formation.

AGEs are permanently modified macromolecule derivatives that form through nonenzymatic glycation of amino groups of proteins. Glycer-AGEs are highly toxic and play an important role in the pathogenesis of chronic inflammatory diseases. However, the contribution of glycer-AGEs to the pathogenesis of uveitis is unclear. In this study, we measured serum levels of glycer-AGEs in 100 patients with endogenous uveitis (22 with HLA-B27-associated uveitis, 20 with VKH disease, 14 with Behçet's disease, and 44 with sarcoidosis) and 33 healthy volunteers. We then examined the effect of the AGE inhibitor in a mouse model of human endogenous uveitis (EAU) by continuous oral administration of pyridoxamine at 200 or 400 mg/kg/day. Regardless of the etiology, serum glycer-AGE levels were significantly higher in patients with uveitis than in healthy subjects. Treatment with 400 mg/kg pyridoxamine significantly reduced the clinical and histological severity of EAU and was accompanied by a significant decrease in serum and retinal glycer-AGE levels and suppression of translocation of NF-κB p65 into the nucleus of retinal cells. Serum glycer-AGE levels may therefore serve as a biomarker of human uveitis, as well as systemic inflammation, and may contribute to the progression of uveitis, including diabetic iritis, via the activation of NF-κB.

Study of the correlation of serum selenium level with Behcet's disease.

BACKGROUND: Selenium, like other trace elements and antioxidant enzymes, is known as an antioxidant and immunomodulator trace element. Due to recent evidence for selenium deficiency in Behcet's syndrome, this study is to evaluate the correlation of serum selenium level with Behcet's disease (BD). MATERIALS: This case-control study was conducted on 46 BD patients and 46 healthy controls in a rheumatology research centre. The case and control groups were both age- and race-matched. Serum selenium level was then measured by atomic absorption spectrometry Shimadzu AA-680. Average serum levels of both groups were then compared and analyzed using t-test. RESULTS: Mean serum selenium levels of patients appeared to be 66.4 ± 15.38 µg/L which was significantly lower than that in the healthy controls (86.87 ± 17.18 µg/L) (P < 0.005). Taking physician global assessment of disease activity into account, significant difference was detected between the patients with active disease (66.57 ± 15.21 µg/L) and those in the inactive state (65.83 ± .75 µg/L). Regardless of the findings mentioned above, serum selenium level was meaningfully elevated among the patients with ocular involvement (P < 0.001). CONCLUSIONS: These findings demonstrated that selenium serum level among BD patients was lower than that in healthy controls, whereas among the patients with ocular involvement it was higher than those not involved.

The association between total antioxidant status and oxidative stress in Behçet's disease.

There has recently been growing evidence supporting the importance of oxidative stress in the pathogenesis of Behçet's disease (BD). In this study, we aim to evaluate total antioxidant status (TAS) and total oxidative stress (TOS) in BD patients, and compare their results both with controls that had recurrent aphthous stomatitis (RAS) and healthy controls. TAS statistically decreased in RAS patients, and TOS levels increased in BD and RAS patients than those in healthy controls. The serum levels of Cu significantly increased only in BD patients when compared with healthy controls. Fe levels were not statistically different among the BD patients, RAS patients and healthy controls, but there was a positive correlation between TOS and plasma Fe levels in BD patients. Our results suggest that there is an insufficient antioxidant system and increased oxidative status both in BD and RAS patients. The antioxidant supplementations in addition to medical treatments will improve the quality of life.

Monozygotic twins concordant for intestinal Behçet's disease.

Although Behçet's disease (BD) is a multisystem disorder of unknown causes, both genetic and environmental factors have been suggested. This is the second reported case of monozygotic twins concordant for Behçet's disease and the first such report of intestinal Behçet's disease. Patient 1 was a 17-year-old man with fever, recurrent oral aphthae, and skin eruptions. He developed hematochezia and was given corticosteroid empirically. One month after he was discharged, he again developed oral ulcerations, fever, and hematochezia. Colonoscopy was performed again, showing aphthous ulcerations in the entire colon, and deep oval ulcers with marginal elevation around the ileocecal valve, which are characteristics of intestinal Behçet's disease. He was treated with colchicine and azathioprine in combination with salazosulfapyridine (SASP) and prednisolone (PSL) and achieved remission. Patient 2 was the twin brother of patient 1. He was admitted because of oral aphthous ulcerations, fever, pustules on his face and body, and genital ulcers. Two weeks later he developed hematochezia. Colonoscopic and barium enema findings were similar to those of his brother. SASP, PSL, colchicines, and azathioprine were also required to achieve remission. Both of the patients were diagnosed with intestinal Behçet's disease. Their monozygosity was confirmed by detailed genetic typing, and HLA-B51 was negative.

Hyperhomocysteinaemia is associated with uveitis but not with deep venous thrombosis in Behcet's disease.

Plasma homocysteine was assessed in Behcet'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 B(12) and folate were assessed by automated immunoassay methods. Hyperhomo-cysteinaemia was defined as plasma homocysteine >15 micromol/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) micromol/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 B(12) and folate. Plasma homocysteine should be measured in patients with BD, and the effect of B-vitamin supplementation should be tested in those with hyperhomo-cysteinaemia.

Serum levels of vitamins A, C, and E, beta-carotene, selenium, and zinc in patients with Behçet's disease: a controlled study.

Behçet's disease is a multisystemic disease characterized by activation and remission periods. The etiopathogenesis is not exactly known; a genetic defect in the immunoregulatory system induced by infectious agents, like viruses and bacteria, is thought to cause the disease. In this study, we examine the serum levels of vitamins A, C, and E, beta-carotene, selenium, and zinc in Behçet's disease patients and investigate the relationship between these serum levels and the activation of the disease. We conclude that adding vitamin E to the treatment of Behçet's disease patients and its effects on the prognosis of the disease need to be further investigated by controlled studies.

Trace elements and antioxidant enzymes in Behçet's disease.

Free oxygen radicals and insufficiency of antioxidant enzymes have been implicated in the pathogenesis of Behçet's disease (BD). Trace elements function as cofactors to antioxidant enzymes. The antioxidant system and trace elements were investigated in many different studies, including BD, but these subjects have not been investigated as a whole in these patients. The aim of the present study was to investigate the antioxidative system and trace elements in BD to contribute to the knowledge of pathogenesis and treatment of this disease. We examined glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities together with selenium (Se), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) levels in plasma and erythrocytes of 50 patients with BD and 30 healthy controls. It was found that in patients with BD, erythrocyte GSH-Px and SOD activities and erythrocyte Se, plasma Fe, Mn, and Zn levels were significantly lower than those of controls and that plasma Cu, erythrocyte Zn, and Mn levels were significantly higher in patients with BD. Insufficient antioxidant enzyme activities were observed in patients with BD. The mechanism(s) of this phenomenon is not clear. Therefore, supplementation with trace elements involved in the antioxidative processes may increase scavenger enzyme activities, and consequently, an improvement in clinical symptoms may be expected.

Erythrocyte antioxidant activity and trace element levels in Behçet's disease.

Selenium (Se), zinc (Zn), copper (Cu), and antioxidant enzyme (superoxide dismutase [SOD] and glutathione peroxidase [GSH-Px]) levels in sera were detected in Behçet patients. Age and sex matched controls were used to find out if oxidative stress takes place in the etiopathogenesis of Behçet's disease. Superoxide dismutase levels were found to be lower in the whole patients group when compared to controls. In whole patients and inactive patients' group Zn and Se levels were found to be higher, but not different in the active patients group when compared to controls. No significant difference was found between the groups as Cu and glutathione peroxidase levels were taken into consideration. According to the results of the present study, SOD level is low in Behçet's disease patients' sera independent from the phase of the disease, and as a result of decreased SOD activity, increased production of free oxygen radicals may play a role in the etiopathogenesis of the disease.

In vitro antioxidant effect of Ginkgo biloba extract (EGb 761) on lipoperoxidation induced by hydrogen peroxide in erythrocytes of Behçet's patients.

Excessive superoxide radical production and an impaired antioxidant mechanism in both the neutrophils and plasma of patients with Behçet's disease (BD) have been reported. To provide clinical support for the earlier data, erythrocyte membrane integrity was investigated by measuring malondialdehyde (MDA, a marker of lipid peroxidation) levels in the erythrocytes of BD patients. In addition, the antioxidant effect of Ginkgo biloba extract (EGb 761) at 25 and 250 microg/ml concentrations on lipoperoxidation induced by hydrogen peroxide (H2O2) in erythrocyte obtained from BD patients was examined in in vitro conditions. When compared to healthy controls, basal erythrocyte MDA levels were found to be higher in BD patients. In the in vitro study, there was also a significant increase in H2O2-induced MDA production in the medium containing no EGb 761 in the patient group, whereas significant decreases in MDA levels were observed in the mediums containing EGb 761 both in the patient and control groups. The decrease in MDA production was found to be related to EGb 761 concentration. These data indicate that an oxidative damage is present in erythrocytes obtained from Behçet's patients, and EGb 761, which may strengthen the antioxidant defense system, may contribute to the treatment of BD.

Oxidative stress and antioxidant defenses in plasma of patients with Behçet's disease.

Plasma myeloperoxidase (MPO) and glutathione peroxidase (GSH-Px) activities, and malondialdehyde (MDA), ceruloplasmin (Cp), transferrin (TF), thiol (SH), selenium (Se) and copper (Cu) levels were determined in patients with Behçet's disease (BD), in order to investigate whether the plasma antioxidant defense system is impaired in BD. When compared to controls, plasma MDA, Cp, Cu levels and also plasma MPO activity were significantly higher in patients, whereas plasma TF, SH and Se levels, and also plasma GSH-Px activity were lower in BD patients than those in controls. In addition, there were significant and positive correlations between MDA-Cp, MDA-Cu, MDA-MPO, MPO-Cp, GSH-Px-Se, Cp-Cu, and TF-SH parameters, but negative correlations between MPO-TF and Cp-TF parameters in BD patients. Based on these findings, it is concluded that plasma antioxidant defense system is insufficient and impaired in BD.

Determination of trace elements in blood serum of patients with Behçet disease by total reflection x-ray fluorescence analysis.

The distribution of trace elements Fe, Cu, Zn, Se, and Rb was determined in sera from patients with the complete type of Behçet disease in the active stage and from healthy controls. Total reflection x-ray fluorescence was used for quantitative analysis; in general, atomic absorption spectrometry was used only for control of the Se values. Zn, Se, and Rb concentrations were significantly (P < 0.0001) lower for patients than for control subjects. No significant difference was determined in the Fe content. However, there was a significant increase in Cu in the patients so that the ratios Cu/Zn, Cu/Se, and Cu/Rb were significantly higher for the patients than for the control subjects (P < 0.0001).

Selenium and Behçet's disease.

Behçet's disease is an inflammatory disorder of unknown etiology, characterized by recurrent oral and genital aphthous ulcers, ocular inflammation, and skin lesions of erythema nodosum and acneiform eruptions. Selenium (Se) affects all components of the immune system, i.e., the development and expression of nonspecific, humoral, and cell-mediated responses. In general, a deficiency in Se appears to result in immunosuppression, whereas supplementation with low doses of Se appears to result in augmentation and/or restoration of immunologic functions. In this study, the distribution of Se and IgG, IgM in serum were compared in samples from healthy adult control and Behçet's disease patients. The serum Se levels were measured by AA-30-40 Varian Spectra, and immunoglobulins were measured by immunodiffusion technique. The mean (SD) serum Se level of 54.24 +/- 8.06 ng/mL among Behçet's disease subjects was significantly different (P less than 0.01) from that in the control subjects (90.01 +/- 9.94 ng/mL). We also measured IgG and IgM as 10.01 +/- 2.74 mg/mL and 1.26 +/- 0.29 mg/mL, respectively for patients, and 15.08 +/- 4.73 mg/mL and 1.58 +/- 0.43 mg/mL for controls. The mean values of IgG and IgM for patients were significantly (P less than 0.05) different from the values of controls. It seems, therefore, that a deficiency in selenium impedes the humoral immune response.

BG-104 enhances the decreased plasma superoxide scavenging activity in patients with Behçet's disease, Sjögren's syndrome or hematological malignancy.

BG-104, a compound of Chinese herbs, has been reported to exert superoxide scavenging activity (SSA) in cell free systems. This report addresses in vivo effects of BG-104 in various disorders. The plasma SSA and laboratory parameters were determined in patients Behçet's disease (BD), Sjögren's syndrome (SjS) or hematological malignancy (M), and the effects of BG-104 treatment on these parameters were studied and compared with those of another antioxidant, vitamin E (alpha-tocopherol). The plasma SSA was significantly lower both in patients with BD and M, and in patients with SjS without antioxidant treatment as compared to that in healthy controls, and it showed an inverse correlation with disease activities. The treatment with BG-104 and/or vitamin E significantly enhanced the plasma SSA in all disorders studied. Both the erythrocyte sedimentation rates, the absolute number of neutrophils, as well as C-reactive protein levels were significantly lower in patients treated with BG-104 and/or vitamin E than those without these drugs. These results indicate that the BG-104 has an anti-inflammatory effect through enhancing plasma SSA in patients with BD, SjS or M.

Behçet's disease. Relation of serum C-reactive protein and erythrocyte sedimentation rates to disease activity.

In a prospective study of 150 patients with Behçet's disease, significant associations were shown between CRP positivity and the presence of erythema nodosum (p less than 0.02) and acute thrombophlebitis (p less than 0.05) and between ESR and erythema nodosum (p less than 0.01), acute thrombophlebitis (p less than 0.001), and acute arthritis (p less than 0.01). Mucocutaneous, ocular, or central nervous system activities did not show significant associations with these indices of inflammation. In 50 patients in whom quantitative CRP determinations were performed, clinical disease activity was accompanied by slight to moderate increases in CRP and ESR.

[Changes in blood calcium, phosphorus and alkaline phosphatase levels in rheumatoid polyarthritis and other types of inflammatory rheumatism]. / Etude des variations de la calcémie, de la phosphorémie et de la phosphatasémie alcaline au cours de la polyarthrite rhumatoide et d'autres rhumatismes inflammatoires.

Albuminemia, calcemia, phosphoremia and alcaline phosphatasemia were measured in three groups of 52 subjects each : rheumatoid arthrits, inflammatory rheumatisms other than rheumatoid arthritis and lumbarthrosics serving as a reference group. Calcemia and albuminemia were significantly lower in patients suffering from rheumatoid arthritis, whose calcemia corrected in relation to albuminemia is, on the other hand, normal : the increase in corrected calcemia pointed out by Kennedy, was not noted. Corrected calcemia was also normal in ankylosing spondylitis, but it was significantly higher in polymyalgia rheumatica. Phosphoremia was shown to be normal but alkaline phosphatases were higher than normal in the three groups.