High-sensitivity C-reactive protein [hs-CRP] in systemic lupus erythematosus patients without cardiac involvement; relation to disease activity, damage and intima-media thickness

To assess the high sensitivity C-reactive protein [hs-CRP level] in systemic lupus erythematosus [SLE] patients without cardiac involvement and find its relation with clinical and laboratory findings, disease activity, damage index and intima-media thickness [IMT]. Forty-five female SLE patients were recruited in the present study without any cardiac involvement. History taking, examination and laboratory investigations were performed for patients. Disease activity was evaluated by the Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] and damage by the Systemic Lupus International Collaborating Clinics [SLICC] index. Thirty age matched female healthy subjects were considered as a control group. hs-CRP was measured quantitatively by microplate immunoenzymometric assay and the IMT measured by ultrasonography. The hs-CRP in the patients was significantly higher [4.84 +/- 3.91 mg/l] compared to the control [1.74 +/- 0.61 mg/l] [p < 0.001]. The IMT in the patients was significantly increased [0.72 +/- 0.37 mm] compared to the control [0.54 +/- 0.15 mm] [p 0.004]. There was no difference in the level of hs-CRP according to the presence or absence of clinical manifestations. However, it was significantly higher in those with positive DNA [5.71 +/- 4.36 mg/L] compared to those with negative results [3.12 +/- 1.97 mg/L] [p 0.009]. There was a significant correlation of the hs-CRP level with the IMT [r 0.49, p 0.001] and SLEDAI [r 0.67, p < 0.001]. These findings suggest that SLE patients without traditional major cardiovascular risk factors may have increased risk of future cardiac events. Measuring hs-CRP may be useful as a marker of disease activity, increased IMT and subclinical atherosclerosis in SLE especially those with positive ds-DNA

Shrinking lung syndrome in systemic lupus erythematosus patients with dyspnea

To identify the frequency of shrinking lung syndrome [SLS] in systemic lupus erythematosus [SLE] with dyspnea and study the clinical characteristics and differences in disease activity and damage. The study included 47 SLE patients complaining of dyspnea. SLS was considered in those with exertional dyspnea, restrictive pulmonary function tests [PFTs] and elevated copula of the diaphragm. Full history taking, thorough clinical examination, laboratory and relevant radiological investigations were performed for all the patients. Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] and Systemic Lupus International Collaborating Clinics [SLICC] indices were compared. High resolution CT chest was performed for patients with radiological findings consistent with SLS. The mean age of the patients was 29.43 +/- 7.45 years, mean disease duration 5.18 +/- 3.62 years. The SLS was present in 8 patients [17.02%]. There was bilateral elevation of the diaphragm copulae in 25% of SLS patients and two had associated basal atelectatic bands. The serum uric acid was significantly higher in those with SLS while the 24 h urine protein was significantly lower and C4 normalized. The levels of SLEDAI and SLICC tended to be lower in those with SLS, yet there was no significant difference from those without. The demographic features, clinical and laboratory manifestations, disease activity and damage scores, PFTs and radiological findings of the SLE patients are presented. In SLE patients with dyspnea, SLS should be looked for as it is present in a high proportion of cases

Clinical significance of serum TNFalpha and -308 G/A promoter polymorphism and serum Il-6 and -174 G/C promoter polymorphism in systemic lupus erythematosus patients

Systemic lupus erythematosus [SLE] is a disorder of immune regulation where cytokine imbalance and genetic factors are implicated in its pathogenesis. To evaluate the clinical significance of serum levels of tumor necrosis factor alpha [TNFalpha] and its -308 G/A promoter polymorphism as well as the IL-6 and -174 promoter polymorphism in SLE patients and find any association to the clinical and laboratory features as well as to the disease activity and severity. We studied 37 female SLE patients and age and gender matched healthy control. Demographic, clinical and serological data were evaluated and the Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] and the Systemic Lupus International Collaboration Clinics/ACR Damage Index [SLICC] were assessed. Serum TNF-alpha and IL-6 levels were measured using enzyme-linked immunosorbent assay [ELISA] and DNA genotyped for TNF-alpha promoter [-308 G/A] and IL-6 promoter [-174 G/C] by polymerase-chain reaction-restriction fragment-length polymorphism [PCR-RFLP] analysis. Serum TNF-alpha and IL-6 levels were significantly higher in the SLE patients compared to control. Regarding IL-6, there was a statistically significant difference between the levels in the three groups according to the promoter polymorphisms. Patients with constitutional symptoms showed higher level of IL-6 while the TNF-alpha level was significantly lower in those with pulmonary manifestations. There was a tendency to a higher TNF-alpha and IL-6 level in those with neuropsychiatric manifestations. Serum TNF-alpha, -308 G/A promoter polymorphism, IL-6 and -174 G/C were higher in SLE patients than in healthy controls. To confirm our results we propose that larger scale, multicenter studies with longer evaluation periods are needed

Juvenile and adult onset systemic lupus erythematosus outcome in Egyptian patients

The aim was to study the outcome characteristics of systemic lupus erythematosus [SLE] in Egyptians according to the age at disease onset and gender. We studied 239 SLE patients [185 adult and 54 Juvenile onset] with a female to male ratio of 9.39-1 and a mean age of 28.23 +/- 8.91 years and disease duration of 5.45 +/- 4.25 years. Full history taking, thorough clinical examination, laboratory and relevant radiological investigations were performed. Disease activity was assessed using SLEDAI and damage by SLICC. Renal biopsies were done in those with renal involvement. The clinical manifestations, disease activity and damage and laboratory investigations of the SLE patients varied according to the age at disease onset and gender. The prevalence of damage was obviously increased in juvenile patients and higher in males. Growth failure, delayed puberty and fibromyalgia were present more in Juvenile-onset patients. Adult onset SLE patients had a significantly higher secondary Sjogren syndrome especially in females. In the present study, there was a 2.5% mortality and the commonly involved kidneys were an important cause of death. Measuring organ damage in SLE is important with special concern to juvenile-onset patients to allow for designing new treatments that improve control of disease activity and minimize the development of irreversible damage. The kidney appeared to be commonly involved, especially in males, indicating the importance of regular screening for early and appropriate management

Sjogren syndrome and fibromyalgia after radioiodine therapy in cancer thyroid patients

Salivary and lacrimal gland dysfunction is relatively frequent after radioiodine therapy. An association of Sjogren's syndrome [SS] and other autoimmune rheumatic diseases as fibromyalgia syndrome [FMS] has been reported. Thyroid autoimmunity in FMS patients is higher than normal subjects. To detect the occurrence of Sjogren syndrome [SS] and any rheumatologic association in cancer thyroid patients after radioactive iodine therapy [I -131] and evaluate the salivary and lacrimal glands function. Thirty-one patients with post-surgical differentiated thyroid carcinomas with a mean age 40.13 +/- 9.82 years, were referred for I-131 therapy [mean dose 212.9 +/- 101.63 mCi] and continued the follow-up study. All patients had no symptoms or signs of SS. Thorough rheumatological examination was performed for any musculoskeletal manifestation or associated fibromyalgia syndrome [FMS]. Before and 8-12 months after I-131 therapy, salivary glands function was estimated by sequential scintigraphy, while lacrimal gland function was assessed by Schirmer's test. Antinuclear antibody [ANA], anti-Ro [SS-A], anti-La [SS-B] and rheumatoid factor [RF] were performed. All patients had a normal salivary glands scintigraphy and Schirmer's test before I-131 therapy. On follow up, primary SS occurred in 8 patients [25.81%] while a significant decrease in salivary function occurred in 18 [58.1%] patients and significantly correlated with the I-131 dose. Schirmer's test was significantly abnormal in those with SS. Serum Anti Ro and Anti La levels became significantly higher in SS patients [18.25 +/- 11.61 and 25 +/- 13.06 U/ml] compared to the others [6.57 +/- 1.8 and 7.35 +/- 1.8 U/ml], respectively, [p 0.025 and 0.006]. Fibromyalgia syndrome was present in 12 patients [38.71%] and 6 of them developed SS. Assessment and follow up of salivary and lacrimal glands function is essential in patients receiving radioiodine therapy. Abnormal level of anti-Ro and Anti-La increase the risk for SS that should be closely monitored and fibromyalgia is a common association

Serum BAFF level and its correlations with various disease parameters in patients with systemic sclerosis and systemic lupus erythematosus

Interest in B-cells has been revived due to the description of new functions. Supporting a role for B-cells in the genesis of autoimmune diseases is the fact that the B-cell-activating factor of the TNF ligand family [BAFF] is essential in their physiology. The role of BAFF, a new cytokine, in autoimmune diseases has been highlighted. To assess serum BAFF level in systemic sclerosis [SSc] and systemic lupus erythematosus [SLE] to verify its role in these diseases and find any relation with the clinical manifestations, laboratory investigations, disease activity and damage. The study included 12 SSc and 40 SLE patients. The patients were subjected to full history taking and thorough clinical rheumatological and dermatological examinations and relevant investigations including autoantibodies and CT chest in SSc. In SSc, the total skin thickness score was scored according to the modified Rodnan skin score [MRSS] method. In SLE, the disease activity was assessed using the Systemic Lupus Activity Measure [SLAM] and organ damage using the Systemic Lupus International Collaborating Clinics/ACR [SLICC/ACR] index. The serum BAFF levels were measured using a specific ELISA. The BAFF level was remarkably elevated in SSc and SLE in a comparable percentage of patients, yet the level was highest in SLE and lower in the limited SSc subtype. The BAFF significantly correlated with the level with the MRSS in SSc and with both the SLAM and SLICC in SLE patients. The elevated level of BAFF in SSc further confirms the importance for new therapeutic targets for its inhibition to slow the disease progression, particularly skin fibrosis. The role of BAFF in the pathogenesis and disease activity in SLE is well-known and the novel noticeable correlation with the damage index high lightens on the utility of BAFF as an indicator of disease damage and predictor of poor outcome

Uterine-umbilical artery doppler velocimetry and pregnancy outcome in SLE patients: relation to disease manifestations and activity

To evaluate the uterine-umbilical artery Doppler velocimetry and determine its relation to pregnancy outcome and disease manifestations in SLE patients. Blood flow velocity waveforms of the umbilical and uterine arteries were studied by color Doppler ultrasound in 36 pregnant SLE patients referred from the Rheumatology Department for follow up and delivery in the Obstetrics Department. Resistance index [RI] and pulsality index [PI] were measured at the 1st week and then every 4 weeks from the 20th and 30th weeks till delivery. The mean age was 27.33 +/- 4.03 years and disease duration of 5.72 +/- 2.57 years. The nulliparity rate and history of previous abortions were higher in those with poor fetal outcome [50% and 62.5%, respectively]. Lupus anticoagulants and anticardiolipin were obviously higher in those with a poor outcome [25% and 37.5%, respectively] with a higher association with APS in spite of anticoagulation. The SLEDAI was higher in those with a poor fetal outcome and the difference reached significance at the 24th week gestation [12.13]. Eight [22.22%] of the patients had abnormal fetal outcome: 5 IUGR [13.89%], 1 IUFD [2.78%] and 2 [5.55%] with missed abortion. Uterine and umbilical artery Doppler abnormalities were higher in those with poor obstetric outcomes and were earlier revealed by the uterine. Uterine artery Doppler seems to be an earlier prognostic factor for adverse outcomes compared to umbilical in SLE patients at high risk, allowing antepartum intensive care and optimal timing of delivery to early confirm a good pregnancy outcome

Myocardial perfusion scintigraphy [Gated-SPECT] and coronary disease risk factors in Behcet's disease with metabolic syndrome

Behcet's disease [BD] is a multi-system vasculitis that can have a wide range of effects on the cardiovascular system. To determine the existence of myocardial perfusion defects caused by coronary microvascular dysfunction in asymptomatic BD patients with and with out metabolic syndrome and to evaluate coronary arterial distribution and left ventricular systolic function by gated single-photon emission computed tomography [G-SPECT]. The study population consisted of 20 [17 men and 3 women] patients with BD and 20 healthy controls of age and sex match. Technetium-99m methoxyisobutylisonitrile [Tc-99m MIBI] gated SPECT studies were performed using a 1-day rest-stress protocol. Stress and rest left ventricular ejection fraction [LVEF] were calculated. Using gated SPECT images myocardial perfusion scores [summed stress score [SSS], summed rest score [SRS] and summed difference score [SDS]] were determined. Echocardiography was performed for comparison. Carotid intima-media thickness [1MT] was recorded to detect the macrovascular involvement in BD and to detect if there is any possible correlation with the microvascular myocardial affection. Abnormal myocardial perfusion scintigraphy [MRS] was detected in 15 patients [2 with infarction, 13 with perfusion defects], 5 patients had normal perfusion pattern. Scmiquantitative scores [SSS, SRS and SDS] were significantly higher in the BD patients compared to control [p 0.000]. There was a statistically significant difference between BD patients and control regarding the carotid artery IMT by ultrasonography being increased in the patients. On the other hand, the G-SPECT and echocardiographic LVEF was significantly lower in the BD patients [p 0.001 and p 0.002 respectively]. On comparing the results of the BD patients with and without metabolic syndrome, the studied parameters for coronary risk factors as blood pressure, cholesterol, triglycerides and fasting blood sugar they were significantly higher in the metabolic syndrome group. On the other hand, the HDE was significantly lower in the metabolic syndrome group. Both the disease activity [BDCAF] and the myocardial perfusion gated SPECT [SSS] were significantly higher in those BD patients with metabolic syndrome [p 0.03]. On the contrary, the differences in results of the carotid artery IMT and the echocardiographic LVEF% in BD patients with and without metabolic syndrome did not reach significance. There was a tendency to increased disease duration in BD patients with more severe myocardial perfusion defect. The difference was only significant between patients with perfusion defect and those with old myocardial infarction involving the antero-septal wall [p 0.04]. There was a statistically significant difference among the three myocardial perfusion scan subgroups as regards the level of triglycerides, systolic and diastolic blood pressure [p 0.29, 0.38, 0.13 respectively]. The CRP level was higher in the infarct patients followed by the defective perfusion. A significant difference was only found when comparing the level of those with history of infarction [severe ischemia] with those with normal myocardial perfusion scan [p 0.047]. On comparing the carotid artery IMT, echocardiographic LVEF%, and myocardial perfusion G-SPECT parameters, they were all significantly different among BD patients with infarction, defective and normal myocardial perfusion. A significant positive correlation was present between the SRS and the disease duration [p 0.04]. CRP significantly correlated with both the SSS and SDS [p 0.04 and 0.00 respectively]. Furthermore, the SSS and SRS significantly correlated with the blood pressure, triglycerides and cholesterol levels. The BDCAF significantly correlated with the SSS and SDS [p 0.009 and 0.007 respectively]. Carotid artery IMT significantly correlated only with SRS [0.02]. However, the echocardiographic LVEF% significantly correlated with all the myocardial perfusion gated SPECT parameters. Myocardial perfusion and function are disturbed owing to influenced coronary microvascularity in BD with silent myocardial ischemia [SMI]. Gated SPECT is a non-invasive more reliable method compared to echocardiography that simultaneously evaluates the existence, extent and severity of myocardial ischemia or infarction in cardio-Behcet. Myocardial perfusion defects increase with increased disease activity and carotid artery IMT. Metabolic syndrome risk factors account for an augmented perfusion defect and should be considered a high risk group in BD patients

Oxidized low-density lipoprotein and carotid intima-media thickness in systemic lupus erythematosus patients: involvement of metabolic syndrome in insulin resistance and atherosclerosis

Traditional risk factors failed to fully account for the premature and accelerated development of atherosclerosis in systemic lupus erythematosus [SLE] patients. The low density lipoprotein [LDL] modification into oxidized LDL [ox-LDL] is a central event in atherogenesis that leads to a cycle of inflammation, endothelial dysfunction and atherosclerotic plaque formation. It is proposed that ox-LDL contributes to the development of autoimmune-mediated atherosclerosis. The metabolic syndrome is closely associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease and is found to be highly prevalent in SLE patients. The aim of the present study was to investigate whether anti-oxLDL antibody [ox-LDL Ab] levels are altered in SLE patients and whether these alterations are related to insulin resistance, atherosclerosis, and components of the metabolic syndrome. Correlation with clinical and laboratory manifestations as well as SLE Disease Activity Index [SLEDAI] and Systemic Lupus International Collaborating Clinics [SLICC]/American College of Rheumatology Damage Index [SLICC/ACR DI] were studied. Thirty SLE women with a mean age of 27.63 +/- 6.11 years, fulfilling the updated ACR revised criteria for the classification of SLE, were recruited from the rheumatology and rehabilitation and internal medicine departments and out patient clinics of Cairo University Hospitals. Consecutive eligible patients, aged >18 years and had disease duration >1 year, were enrolled. Exclusion criteria included overlap syndrome, serum creatinine > 1.4 mg/dl, proteinuria > 0.15 g/24 hour, pregnancy, cancer, cirrhosis, history of myocardial infarction, angina, stroke or receiving insulin. Ten age and sex matched healthy volunteers served as controls with a mean age of 27.8 +/- 4.61 years. Full history taking, clinical examination and investigations were performed for all the patients. Disease activity and damage were assessed by SLEDAI and SLICC/ACR DI respectively. The Adult Treatment Panel [ATP III] criteria were used to define the presence of metabolic syndrome in SLE patients. Levels of insulin, glucose, creatinine, lipid profile as well as, ox-LDL Ab were measured in patients and control. Insulin sensitivity was estimated using the homeostatic model assessment index [HOMA-B] for beta cell function and [HOMA-IR] for peripheral tissue insulin resistance. Intima-media thickness [IMT] of the carotid artery was measured in both patients and control by ultrasonography. Patients with SLE had significantly higher mean values of HOMA-IR, HOMA-B, ox-LDL Ab and intima-media thickness [IMT]. The mean IMT in the SLE patients was 0.74 +/- 0.38 mm vs 0.25 +/- 0.09 mm in the control. Moreover, the circulating serum ox-LDL level in SLE patients was significantly higher compared to control subjects [37.18 +/- 10.85 EU/ml vs. 14.18 +/- 2.42 EU/ml, respectively]. On classifying SLE patients according to the presence or absence of metabolic syndrome, the mean ox-LDL Ab level was significantly higher in patients with metabolic syndrome [n = 11] compared to those without metabolic syndrome [n = 19]. While, no statistically, significant difference was observed between both groups either in SLE disease activity index [SLEDAI], damage index [SLICC/DI], HOMA-IR, HOMA-B or IMT. Correlation of the metabolic features and IMT of the SLE patients with the studied parameters revealed a significant positive correlation between the ox-LDL and the waist-hip ratio, HOMA-IR, SLEDAI, SLICC/DI indices as well as IMT. Beta cell function significantly negatively correlated with the dose of administered steroids. Furthermore,' IMT significantly positively correlated with the SLEDAI and SLICC/DI respectively. It could be concluded that serum ox-LDL is altered in SLE patients especially with metabolic syndrome and is correlated with insulin resistance and atherosclerosis as well as SLE activity and damage indices. Additionally, IMT is increased in SLE patients. Both serum ox-LDL level and IMT measurement are recommended in SLE patients and could be used as useful markers for predicting future cardiovascular events especially in the absence of symptoms of CVD

Verification of subclinical atherosclerosis by carotid doppler ultrasonography in behcet disease patients

Behcets disease [BD], is a unique systemic vasculitis, which affects almost all types and sizes of blood vessels. Although the exact pathogenesis of BD remains unclear, small vessel vasculitis accounts for a considerable portion of the pathogenic processes in BD. In addition, large venous or arterial lesions can occur in BD patients and vascular involvement may be seen in 25%. Vasculitis makes the prognosis of BD severe. Doppler ultrasonography may show carotid intima-media thickness [IMT] associated with atherosclerosis in BD which is an endothelial cell dysfunction [ECD] parameter and may partially explain the observed cardiovascular morbidity and mortality. The aim of the present work is to study the use of Doppler ultrasonography in the assessment of the carotid artery involvement regarding the IMT and plaque formation in patients with BD. Correlation with disease activity, clinical manifestations and laboratory investigations were considered. Assessment of the lipid profile of the patients and correlation with the findings of the Doppler ultrasonography was considered. Twenty patients, 15 males and 5 females, suffering from BD satisfying the new set of diagnostic criteria published by the International Study Group for Behcet's Disease in 1990, were included in the present study. They were recruited from the Rheumatology and Rehabilitation department as well as the outpatient clinic, Cairo University hospitals. Patients were taken consecutively, with a mean age of 36.75 +/- 8.57 years [ranged from 22 to 54 years] and mean disease duration of 9.23 +/- 5.83 years [range 1.5 to 20 years]. Twenty age and sex matched healthy volunteers served as controls with a mean age of 34.5 +/- 4.24 years were also included in the present study. Subjects with diabetes mellitus, hypertension or evidence of myocardial infarction were excluded from the study. Full history taking and clinical examination of all patients and investigations including lipid profile were performed for the control and the patients. Medications received by the patients were considered and patients receiving corticosteroids for management of their disease were not excluded. Disease activity was assessed using the Behcets disease current activity form [BDCAF] score. Carotid artery ultrasound scan for the right and left common carotid arteries, carotid bulb and the first 1.5 cm of the internal and external carotid arteries was carried out in the radiodiagnosis department, Cairo University. The IMT of the carotid artery was measured in both patients and control by ultrasonography. The age at disease onset was 27.53 +/- 6.46 years. Six of the patients were smokers. There was no significant correlation between the dose of corticosteroids or colchicine used by the BD patients and the IMT of the carotid artery. However, the dose of steroids significantly positively correlated with the level of low density lipoprotein [LDL] [p = 0.013]. The mean IMT of both right and left carotid arteries in the BD patients was 0.64 +/- 0.32 mm [0.68 +/- 0.38 mm and 0.6 +/- 0.24mm for the right and left IMT respectively]. The IMT of BD patients was significantly different from that in the control subjects [0.42 +/- 0.13 mm] [p = 0.003]. There was no significant difference between smoker and non smoker patients [p = 0.1]. Furthermore, there was no significant correlation between the IMT with the disease duration or BMI [p = 0.46 and 0.3 respectively].The IMT of the carotid artery showed a significant positive correlation with the urea level [p = 0.009] and creatinine [p = 0.013]. There was a tendancy towards a positive correlation between the IMT and the cholesterol level and a negative one with the HDL, however, there was a significant positive correlation with the serum triglycerides [p = 0.03]. There were positive sonographic findings in 3 out of 20 BD patients [15%] compared to the control [0%]. The three patients were two males who had autoimmune hepatitis and one female with HCV positive hepatomegaly. Atherosclerotic plaque was present in two. There was a significant positive correlation between the IMT of the carotid artery and the BDCAF score in BD patients [r = 0.481, p = 0.016]. The score significantly negatively correlated with the platelet count [p = 0.002] while there was no correlation with the cholesterol, triglycerides, low or high density lipoprotein. On comparing the IMT in BD patients according to the presence and absence of arthritis, CNS or eye involvement, there was no significant difference. One can conclude that there is a morphologic evidence of subclinical atherosclerosis in patients with BD. IMT was associated with triglycerides as well as urea and creatinine levels denoting that the renal function forms a possible risk of CVD in BD. The BDCAF is an easy tool that may significantly reflect the cardiovascular involvement in BD patients and may be important for clinical management