Valvular heart disease as a cause of cerebrovascular disease in patients with systemic lupus erythematosus

Thirty-seven patients with systemic lupus erythematosus underwent complete clinical and laboratory evaluations, including antiphospholipid antibodies and lupus anticoagulant, magnetic resonance imaging of the brain, and transesophageal echocardiography. Cerebrovascular disease manifested as stroke, transient ischemic attack, or cerebral infarcts in patients with nonfocal neurologic deficits was detected in 19 patients (51%), and significant left-sided valvular heart disease in 25 (68%). Valve vegetations, valve thickening, valve regurgitation, and lupus anticoagulant antibody occurred 2 to 3 times more often in patients with than without cerebrovascular disease (all p < or =0.04) and were the only independent predictors of cerebrovascular disease (odd ratios 5.3 to 10.6, all p < or =0.03). Thus, valvular heart disease probably exacerbated by hypercoagulability appears to be a source of embolic ischemic brain injury and cerebrovascular disease.     

Clinically significant valvular heart disease in systemic lupus erythematosus

PURPOSE: Clinically significant valvular heart disease due to systemic lupus erythematosus (SLE) has generally been considered rare, and Libman-Sacks endocarditis has been thought to be predominantly an autopsy finding. With the declining prevalence of rheumatic heart disease, however, the spectrum of valvular heart disease is changing. We retrospectively analyzed our experience with SLE between 1975 and 1987 for the presence of hemodynamically significant valvular heart disease. PATIENTS AND METHODS: An existing data base of 421 patients with SLE was selected for review. Patients were selected for inclusion in the study if they met four or more of the criteria of the American Rheumatism Association for SLE, they had clinically significant valvular heart disease, and tissue from the involved valve was available for review. The etiology of the valve lesion was determined by assessment of the clinical history, chart review, gross morphology, and valve histology. RESULTS: Of 14 cases with pathologic material available for review, six had anatomic features of SLE valvular heart disease such as verrucous vegetations or valvulitis with necrosis and vasculitis. Two of these patients underwent successful valve replacements and four died from complications of their valve disease. CONCLUSION: We suggest that significant morbidity and mortality may result from SLE valvular heart disease in about 1 to 2 percent of SLE patients and that the pathogenetic mechanisms underlying valve dysfunction in SLE patients are multifactorial.     

Novel therapeutic agents for systemic lupus erythematosus

The last significant breakthrough in the treatment of systemic lupus erythematosus (SLE) was the use of cyclophosphamide and methylprednisolone in the treatment of lupus nephritis. Recent advances in immunology, oncology, and endocrinology have resulted in many potential therapies for SLE. These therapies include new immunosuppressants, biologic medications, tolerizing agents, immunoablation techniques, and hormonal medications. Each of these approaches will be discussed in this review. Some therapies are currently in use in clinical rheumatology practice (mycophenolate mofetil) and others are entering phase I trials (anti-BLyS monoclonal antibody). While some of these new therapies target specific inflammatory mechanisms in SLE (anti-CD40L monoclonal antibody), others work by nonspecific inhibition of the immune system (immunoablation).     

Newer therapeutic approaches for systemic lupus erythematosus

In recent years, advances in the treatment of systemic lupus erythematosus (SLE) refractory to conventional therapy have been suggested in anecdotal series and some clinical trials. A number of promising agents have been studied only in murine models of SLE, and clinical trials are awaited. Rigorously conducted clinical trials must be completed to advance these studies to the point that new therapies for SLE will be approved.     

Crohn's disease and systemic lupus erythematosus

A 28-year-old man with inflammatory bowel disease with complex extraintestinal involvement was found to have diagnostic features of both systemic lupus erythematosus and Crohn's disease. Although some of the systemic complications of these diseases may overlap, both diseases may occur as primary disorders. Coexistence of systemic lupus erythematosus should be considered in patients with inflammatory bowel disease and complex extraintestinal manifestations.     

Association of lupus anticoagulant with severe valvular heart disease in systemic lupus erythematosus

Two cases of systemic lupus erythematosus with hemodynamically significant mitral valve dysfunction and associated lupus anticoagulant are reported. Both patients underwent valve replacement and both had thrombus formation on the mitral valve, one pre- and the other postoperatively. Both patients suffered a number of extracardiac thromboses at different times in the course of their illness. The contribution of the lupus anticoagulant to the thrombotic problems, and its possible relationship to the pathogenesis of Libman-Sacks endocarditis are discussed.     

Kidney disease in systemic lupus erythematosus

Summary Glomerulonephritis is a major determinant of outcome in patients with systemic lupus erythematosus. Persistently active lupus nephritis imposes serious threats of end-stage renal failure and cardiovascular morbidity. Sustained corticosteroid treatment has been characterized as having an uncertain net benefit on the control of lupus nephritis, mainly because these drugs have relatively weak efficacy and they have been shown to confer their own set of cardiovascular risk factors. Controlled trials of corticosteroids, azathioprine and cyclophosphamide have demonstrated that the best control of clinical activity of proliferative lupus nephritis is attained with cyclophosphamide. To date, intermittent pulse cyclophosphamide treatment has produced the most facorable balance of efficacy and toxicity in patients with lupus nephritis.     

Pulmonary disease in systemic lupus erythematosus

Pulmonary problems are common in systemic lupus erythematosus, and may be the presenting feature of this multi-system disease. The clinical spectrum ranges from mild, self-limited, pleuritic chest pain to fulminant and rapidly fatal, diffuse, pulmonary hemorrhage. Accordingly, treatment must be individually tailored to the clinical features of each patient. Non-steroidal-anti-inflammatory drugs may be adequate therapy for pleuritic pain. High dose corticosteroids may be indicated in more severe cases of pleurisy with effusion, lupus pneumonitis, and diffuse interstitial lung disease. Immunosuppressive drugs such as azathioprine and cyclophosphamide should be considered in cases of lupus pneumonitis or interstitial lung disease unresponsive to steroids. Combined therapy with corticosteroids, immunosuppressives and plasmapheresis should be considered for fulminant cases of diffuse pulmonary hemorrhage attributed to lupus. There is no definitive therapy for pulmonary hypertension at this time. Decisions regarding treatment in each instance must be made with the recognition that there is little strong clinical evidence to support the use of any of these therapies. Finally, no pulmonary process should be attributed to lupus until infection has been rigorously excluded in these patients.     

Complete heart block and systemic lupus erythematosus.

An 18-year-old girl with systemic lupus erythematosus developed progressive electrocardiographic abnormalities over a period of 16 years, culminating in complete heart block with Adams-Stokes attacks. A permanent ventricular pacing system was implanted successfully.     

Kawasaki disease and juvenile systemic lupus erythematosus

Kawasaki disease (KD) is a common vasculitis in childhood. To the authors' knowledge, only one case of juvenile systemic lupus erythematosus (JSLE)-like onset mimicking KD and another case of KD and JSLE association have previously been described. However, the prevalence of this association of the two diseases was not reported. Therefore, over 27 consecutive years, 5419 patients were followed at the Pediatric Rheumatology Unit and 271 (5%) of them met the ACR classification criteria for JSLE. Two (0.7%) of them were female. These also had KD according to European League against Rheumatism / Paediatric Rheumatology European Society (EULAR/PReS) consensus criteria and are described in this report. One case was a 13-year-old who presented all six KD criteria. Echocardiogram showed pericardial effusion, dilatation and tortuosity of right and left coronary, and her symptoms promptly improved after treatment with intravenous immunoglobulin (IVIG). Lupus diagnosis was established a few days later. Another case was a 4-year-old who had also met all six KD criteria, with improvement after IVIG, and lupus diagnosis was made 1 year later. In conclusion, the frequency of the association between these two autoimmune diseases was rare. The occurrence of a second autoimmune systemic disease in a patient with a history of KD should also be considered. Furthermore, the initial presentation of lupus may mimic KD.     

Complete heart block and systemic lupus erythematosus.

An 18-year-old girl with systemic lupus erythematosus developed progressive electrocardiographic abnormalities over a period of 16 years, culminating in complete heart block with Adams-Stokes attacks. A permanent ventricular pacing system was implanted successfully.     

Valvular lesions in patients with systemic lupus erythematosus and antiphospholipid syndrome: an old disease but a persistent challenge

Valvular heart disease is common in systemic lupus erythematosus (SLE) and antiphospholipid syndrome. Immunologic insult plays a fundamental role in its pathogenesis but data on the role of antiphospholipid antibodies have been inconsistent, particularly regarding SLE-associated valvular lesions. Although timely diagnosis is essential to prevent progression of valvular lesions, treatment remains a challenge because of the lack of large systematic studies. This article reviews and summarizes recent information relating to valvular damage in these two autoimmune diseases, and highlights some important questions that need to be answered.