Peripheral vascular disease in systemic lupus erythematosus

With increasing longevity of lupus patients, peripheral vascular disease (PVD) has become an important cause of morbidity. With no systematic study of PVD in systemic lupus erythematosus (SLE), this study was undertaken to define the frequency and spectrum of PVD in SLE and factors affecting such an occurrence. All medium-sized peripheral arteries of bilateral upper and lower extremities were studied in 50 SLE patients using Doppler ultrasonography. PVD was defined clinically as one or more of intermittent claudication, absent/unequal pulses, gangrene or ischemic ulcers and sub-clinically as asymptomatic patients with Doppler abnormalities, with > or =50% reduction in diameter considered hemodynamically significant. Mean (SD) age of the patients was 31.6 (10.1) years. Forty-one percent were hypertensive. Dyslipidemia was found in 62%. Fifteen (30%) had Raynaud's phenomenon. Fourteen (28%) patients had PVD, of whom three had positive markers for antiphospholipid antibody (aPL) and six were asymptomatic. Ischemic ulcers were seen in eight (16%), gangrene in three (6%), femoral artery plaques in two (4%), stenosis in four (8%) and intermittent claudication in none. Dyslipidemia was found to independently affect occurrence of PVD (OR = 5.37, [95% CI 1.05-27.5], P = 0.05). The causes of PVD overlap significantly and further studies are needed to ascertain the relative contribution of each.     

Update on vascular disease in systemic lupus erythematosus

PURPOSE OF REVIEW: Young women with systemic lupus erythematosus have strikingly high rates of coronary heart disease. Current knowledge indicates that atherosclerosis is an active inflammatory and immune-mediated process. Therefore, the chronic inflammation and immune dysregulation characteristic of systemic lupus erythematosus undoubtedly contribute to the accelerated vascular disease seen in these patients. Carefully considering what is known about atherogenesis in the general population will provide clues to unraveling the complexity of why systemic lupus erythematosus and atherosclerosis are linked so frequently. RECENT FINDINGS: Inflammation is involved in all aspects of atherogenesis from the initial endothelial "response to injury," to foam cell formation leading to the atherosclerotic lesion, to the rupture of the "vulnerable" fibrous cap, resulting in the acute coronary syndrome and potentially in death. The authors review how factors commonly seen in systemic lupus erythematosus or inherent to the underlying disease mechanism may contribute to each of the stages of atherogenesis. SUMMARY: Our focus on the causes of vascular disease in systemic lupus erythematosus must now include nontraditional risk factors such as immune and inflammatory mediators. With the advent of noninvasive screening tools for atherosclerosis, we are better equipped to measure subclinical vascular disease and associated risk factors, including immune and inflammatory mediators. When considering strategies for preventing premature cardiovascular disease in systemic lupus erythematosus, modifying immune and inflammatory risk factors will likely become a major component of the program in addition to modifying the current traditional risk factors.     

Retinal disease in patients with systemic lupus erythematosus

OBJECTIVE: To investigate the incidence of retinopathy in systemic lupus erythematosus (SLE) and to clarify its significance in relation to other clinical manifestations. METHODS: A cross sectional study on lupus retinopathy was made in 69 patients with SLE. One expert ophthalmologist examined the ocular fundi of the lupus patients without any information of their disease state. Clinical and laboratory findings in the patients with retinopathy and those without were compared. RESULTS: Retinopathy was found in 7/69 (10%) patients. The findings included haemorrhages, vasculitis, cotton wool spots, and hard exudates, all of which were considered to reflect vascular damage. Retinopathy was found to be associated with the presence of anticardiolipin antibody (p<0.05) and with central nervous system lupus (p<0.01). The patients with retinopathy had higher levels of serum creatinine than the patients without retinopathy (p<0.01). The disease activity of lupus, as assessed by the maximum SLE disease activity index (SLEDAI) score of the patients, was also significantly higher in the patients with retinopathy (p<0.03). CONCLUSION: Incidence of retinopathy in SLE was similar to that in previous reports and it may reflect tissue microangiopathy, particularly associated with vasculitis or anticardiolipin antibodies, or both.     

Association of antiphospholipid antibodies with retinal vascular disease in systemic lupus erythematosus.

OBJECTIVES: To study the prevalence and characteristics of retinal vascular disease in patients with systemic lupus erythematosus (SLE) and to analyze their relationship with antiphospholipid antibodies (aPL) and other serological markers. PATIENTS AND METHODS: Eighty-two consecutive patients (77 women and 5 men; mean age, 36 years) were studied. All patients fulfilled the 1982 revised criteria of the American College of Rheumatology for the classification of SLE. Ophthalmologic examination included assessment of best corrected visual acuity, tonometry, slit-lamp biomicroscopy, and fundus examination. Serologic studies included determination of anticardiolipin antibodies (aCL) (ELISA), lupus anticoagulant (LA) (coagulation tests), antinuclear antibodies (indirect immunofluorescence), anti-DNA (Farr's test), and anti-ENA antibodies (counterimmunoelectrophoresis). RESULTS: Retinal vascular disease was detected in 13 (15%) of 82 SLE patients. The retinal lesions consisted of retinal vascular occlusions in six patients (five arterial and one venous), cotton-wool spots in three, optic disc edema in three, retinal hemorrhages in three, and ischemic optic neuropathy in one. Antiphospholipid antibodies were detected in 10 (77%) of these 13 patients: nine had aCL and two had the LA. When compared with patients without retinal vascular disease, patients with retinopathy had a higher prevalence of aPL (77% v. 29%, P = .005). CONCLUSIONS: Retinal vascular disease is frequent in patients with SLE. The presence of aPL is associated with a higher prevalence of retinal abnormalities in SLE patients.     

Tuberculosis in patients with systemic lupus erythematosus.

Tuberculosis associated with systemic lupus erythematosus (SLE) was studied in a cohort of 311 patients seen between 1963 to 1979. There were 16 such patients, giving rise to a prevalence rate of 5%. The characteristics of SLE-associated tuberculosis include a high incidence of miliary and far-advanced pulmonary disease, delay in establishing diagnosis, especially the extrapulmonary form, and tendency to attribute symptoms like fever, malaise, and weight loss to the lupus process. Treatment was successful in 9 patients. Of the 7 death 5 were attributed directly to the mycobacterial infection and 2 to complications of SLE.     

Damage in cuban patients with systemic lupus erythematosus. Relation with disease features

ObjectiveTo determine damage presence and predictors factors for its appearance in a cohort of cuban patients with systemic lupus erythematosus (SLE).Patients and methodsA retrospective cohort study included 80 patients presenting with SLE seen in Rheumatology Service of “Hermanos Ameijeiras” Clinical Surgical Hospital in Havana City, Cuba. Damage was assessed using The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (SLIC/ACR), a tool approved for damage measurement. Damage presence was related to initial disease features to diagnose this condition, to sociodemographic elements, to treatments used, and to the disease course time. Statistical analysis had two variants: the univariate and multivariate type using Chi2 and statistical significance was established in p<0, 05.ResultsWe found that 39 patients (48,8%) had some degree of damage. More involved domains were the musculoskeletal (18,8%), neuropsychiatric, and skin, 16,3%, pulmonary and ocular, present in 15% of cases. In the multivariate analysis, damage was associated with the use of higher than 30 mg/day Prednisone doses for more of 4 weeks (OR=54,68, CI 95%=3,56–97,45, p=0.001), presence of leukopenia (RO=18,73, CI 95%=2,74–62,23 m p=0,004), and time course of disease (OR=1,02, CI 95%=1,00 2–1,09, p=0.006). Conclusions: Damage was practically present in half of the study patients, the most involved domain was the musculoskeletal, and use of higher than 30 mg prednisone doses were the factor most associated with the presence of damage.     

Haemostatic factors associated with vascular thrombosis in patients with systemic lupus erythematosus and the lupus anticoagulant.

To elucidate the mechanism of vascular thrombosis in patients with systemic lupus erythematosus and the lupus anticoagulant changes in factors associated with haemostasis were investigated. The lupus anticoagulant was associated with an increased incidence of thrombosis, particularly cerebral thrombosis. Concentrations of fibrinopeptide A and fibrinopeptide B beta 15-42 were significantly raised in the plasma of patients with systemic lupus erythematosus and the anticoagulant compared with concentrations in patients without the lupus anticoagulant. The tendency towards formation of thrombosis was not found in all lupus patients with the anticoagulant, however. Concentrations of thromboxane B2 were remarkably raised in the plasma of the two patients with the lupus anticoagulant who had recently had thrombosis. Concentrations of 6-keto-prostaglandin F1 alpha, protein C, antithrombin III, and plasminogen were similar in both groups. No significant decrease in serum stimulatory activity on prostacyclin production by cultured aortic endothelial cells was noted in lupus patients with the anticoagulant, but inhibition was present in the two patients with recent thrombosis. These results indicate that although patients with the lupus anticoagulant are not always in a hypercoagulable state, haemostatic abnormalities found in some patients with the anticoagulant may be predictive of thrombotic events.     

Liver hemangioma and vascular liver diseases in patients with systemic lupus erythematosus

AIM:To investigate whether systemic lupus erythematosus (SLE) is associated with benign focal liver lesions and vascular liver diseases, since these have been occasionally reported in SLE patients. METHODS:Thirty-five consecutive adult patients with SLE and 35 age-and sex-matched healthy controls were evaluated. Hepatic and portal vein patency and presence of focal liver lesions were studied by colour-Doppler ultrasound, computerized tomography and magnetic resonance were used to refine the diagnosis, clini...     

Cardiac abnormalities in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of cardiac abnormalities in patients with systemic lupus erythematosus. DESIGN: Prospective survey. SETTING: Rheumatic diseases unit of a university hospital. PATIENTS: Volunteer sample comprising 83% of patients with systemic lupus erythematosus followed annually in the rheumatic disease unit (93 patients; mean age 46 +/- 13 years; female 79, male 14). These patients were age-matched with 16 female control volunteers (mean age 43 +/- 5 years) recruited from hospital staff. INTERVENTIONS: Electrocardiograms, two-dimensional echocardiograms and radionuclide angiograms were performed in patients and controls. Anticardiolipin antibodies were measured by enzyme-linked immunosorbent assay in the systemic lupus erythematosus patients. MAIN RESULTS: At least one cardiac abnormality was detected in 44 of 93 systemic lupus erythematosus patients (47%). These abnormalities included: aortic valve thickening 12%; mitral valve thickening, prolapse, vegetations or stenosis 23%; left ventricular segmental dysfunction 4%; left ventricular global hypokinesis 4%; right ventricular hypokinesis 4%; left ventricular hypertrophy 14%; left ventricular diastolic dysfunction 16%; and pericardial effusion 2%. Three of the 16 controls (19%) had cardiac abnormalities consisting of mitral valve prolapse (one), right ventricular hypokinesis (one) and pericardial effusion (one). Cardiac abnormalities were more common in the systemic lupus erythematosus group compared with controls (47% versus 19%, P less than 0.05). Raised anticardiolipin antibodies were specific (88%) but not sensitive (33%) for the presence of cardiac abnormalities in systemic lupus erythematosus patients. Renal disease and prednisone therapy were more common in systemic lupus erythematosus patients with cardiac involvement than in such patients without evidence of cardiac disease (40% versus 16%, P = 0.03; and 81% versus 59%, P = 0.04, respectively). CONCLUSIONS: Cardiac abnormalities can be identified noninvasively in 47% of patients with systemic lupus erythematosus.     

Cognitive impairment in patients with systemic lupus erythematosus.

Seventy unselected patients with systemic lupus erythematosus (SLE) were studied to determine the prevalence of cognitive impairment and the association with other clinical variables. Twenty-five patients with rheumatoid arthritis (RA) and 23 healthy subjects were used as controls. All patients were evaluated with a battery of standardized neuropsychological tests to determine ability in 8 areas of cognitive function. Clinically overt neuropsychiatric (NP) SLE, cumulative disease manifestations and concurrent medications were documented. In patients with SLE, generalized disease activity was expressed using the SLE disease activity index. Cognitive impairment was identified in 15/70 (21%) patients with SLE, 1/25 (4%) patients with RA and in 1/23 (4%) healthy subjects (p = 0.042). The prevalence was higher in patients with active NP-SLE at the time of assessment (2/5, 40%) compared to patients with inactive NP-SLE (2/10, 20%) but was also increased in those patients who had never had known clinical NP-SLE (11/55, 20%). A history of serositis (p = 0.015), active SLE (p = 0.064) and corticosteroid use (p = 0.027) at the time of assessment were more common in patients with cognitive impairment. The results suggest that cognitive impairment is increased in patients with SLE. It may occur independently of clinically overt NP-SLE and is more common in patients with active disease who are receiving corticosteroids.     

Risk factors for coronary artery disease in patients with systemic lupus erythematosus.

PURPOSE: To estimate the frequency of and examine risk factors for coronary artery disease (CAD) in patients with systemic lupus erythematosus (SLE) in a prospective longitudinal study. PATIENTS AND METHODS: Patients were SLE are enrolled in The Johns Hopkins Lupus Cohort, a prospective study of outcomes in 229 subjects with SLE. CAD was defined as angina, myocardial infarction, or sudden death. Data on CAD risk factors were obtained prospectively every 3 months and were analyzed using univariate and multiple logistic regression. RESULTS: CAD occurred in 19 (8.3%) of 229 patients with SLE and accounted for 3 (30%) of 10 deaths as of December 31, 1990. Compared to subjects without CAD, those with CAD were more likely to have been older at both diagnosis of SLE (37.1 years versus 28.9 years, p = 0.004) and at entry into the cohort (47.1 years versus 34.7 years, p < 0.0001), to have a longer mean duration of SLE (12.3 years versus 8.1 years, p = 0.013) and a longer mean duration of prednisone use (14.3 years versus 7.2 years, p < 0.0001), to have a higher mean serum cholesterol (271.2 mg/dL versus 214.9 mg/dL, p < 0.0001) or a cholesterol level greater than 200 mg/dL (odds ratio [OR] 14.5, 95% confidence intervals [CI] 1.9, 112.1), and to have both a history of hypertension (OR 3.5, 95% CI 1.3, 9.6) and a history of use of antihypertensive medications (OR 5.5, 95% CI 1.8, 17.2). There were no significant associations with other known CAD risk factors such as smoking, diabetes, family history of CAD, race, or sex, or variables related to steroid therapy including the presence of cushingoid features or ever use of corticosteroids. The best multiple logistic regression model for CAD included age at diagnosis, duration of prednisone use, requirement for antihypertensive treatment, maximum cholesterol level, and obesity (using NHANES-II [National Health and Nutrition Examination Survey] definitions). CONCLUSION: Primary and secondary prevention strategies directed at hypertension, hypercholesterolemia, and obesity, as well as other known CAD risk factors, should be routinely employed in the management of patients with SLE.