Chapter 256. Systemic Lupus Erythematosus

1. Does this patient have systemic lupus erythematosus (SLE)?

2. Has SLE disease activity led to this patient's hospitalization?

3. How should flares of SLE be managed?

4. How does treatment of other diseases affect the status of SLE?

5. What are possible adverse consequences of the treatment of SLE?

6. How should medications for SLE be managed upon hospital discharge?

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects about 1 in 2000 individuals. Women of childbearing age are most commonly affected. SLE can manifest in any organ system, and disease activity varies over time. Phenotypically, SLE is highly variable and may affect some organ systems but not others in certain individuals. Both the incidence and severity of SLE are increased in individuals of African or Caribbean descent, as well as in Hispanic populations within the United States.

In the past, SLE had relatively high mortality and morbidity rates. Recent estimates place 5-year survival rates around 95% and 20-year survival rates around 80%. As survival rates have improved in individuals with SLE, so have hospitalization rates. Most hospitalists care for individuals with active SLE during the course of a year. In one retrospective analysis, more than half the patients in a lupus cohort were hospitalized at some point over the previous two years. The most common reason for hospitalization in patients with SLE is disease flare. Patients are also commonly admitted for complications of SLE or its treatment, such as infections and cardiovascular and thromboembolic disease. Individuals with SLE are at high risk for premature atherosclerosis and may be admitted with chest pain, acute coronary syndromes, or cerebrovascular accidents. As well, patients may be first diagnosed with SLE when hospitalized for a severe disease manifestation, such as pericarditis, glomerulonephritis, or neurologic disease.

Autoimmune diseases are thought to occur when an environmental trigger, such as infection, sunlight, or smoking, activates an abnormal immune response in a genetically susceptible individual. Abnormalities in nearly every aspect of immune system function have been demonstrated either in humans or in animal models of SLE.

The serologic hallmark of SLE is the presence of serum autoantibodies, generally against nuclear proteins. The pathogenesis of autoantibodies may relate to defective clearance of apoptotic cells. When cells undergo apoptosis, internal proteins are displayed on surface blebs. If the apoptotic cells are not cleared, nuclear material is exposed to the immune system, which may become sensitized. Certain complement component deficiencies, namely of C4 and C1q, are associated with SLE; this may relate to the role of complement activation in clearing apoptotic cells and foreign antigens.

Autoantibodies can cause tissue damage through direct binding and subsequent immune system activation, or via formation and deposition of immune complexes in tissues. Autoantibodies are implicated in multiple manifestations of SLE, including glomerulonephritis, cutaneous lupus, cytopenias, and thrombosis. Anti–double stranded DNA (dsDNA) antibodies are associated with lupus nephritis, though glomerulonephritis can also occur in the absence of anti-dsDNA antibodies, likely mediated ...