Medical Grand Rounds

Lupus update: Perspective and clinical pearls

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LUPUS SURVIVAL HAS IMPROVED; DISEASES OF AGING NOW A FOCUS

In 1950, only 50% of patients with SLE survived 5 years after diagnosis; now, thanks to better treatment and earlier diagnosis, 80% to 90% survive at least 10 years.

Early on, patients tend to die of active disease (manifestations of vasculitis, pulmonary hemorrhage, kidney problems) or infection. Over time, cardiovascular disease and osteoporosis become more of a problem. Patients also have a higher risk of cancer throughout life.

Lupus has an unpredictable course, with flares and remissions. But underlying the reversible inflammatory changes is irreversible organ damage caused by the disease itself and, possibly, by treatment. Preventing bone disease, heart disease, and cancer now play more prominent roles in managing SLE.

Increased bone disease

Fracture rates are higher than expected in women with lupus; Ramsey-Goldman et al8 calculated the rate as five times higher than in the general population. The increased risk of osteoporosis is partly due to treatment with corticosteroids, but it is also likely caused by inflammation from lupus. Even controlling for steroid use, increased bone loss is still evident in patients with SLE.

African American women with lupus are not exempt. Lee et al9 found that, after adjusting for body mass, steroid use, thyroid disease, and menopausal status, African American women with SLE had more than five times the risk of low bone mineral density in the spine than white women with the disease.

Increased cancer risk

Patients with SLE have an increased risk of hematologic cancer and possibly lung and hepatobiliary cancers.

Bernatsky et al10 evaluated cancer risk in an international cohort of patients with SLE from 23 sites. Among patients with SLE, for all cancers combined, the standardized incidence ratio was 1.2; for hematologic cancers the ratio was 2.8; and for non-Hodgkin lymphoma it was 2.4. Surprisingly, although SLE is primarily a disease of women, reproductive cancer rates in patients with SLE did not differ from background rates. Bernatsky et al did not compare rates of cervical cancer, as many cancer registries do not record it. However, studies from the National Institutes of Health indicate that cervical dysplasia is common in patients with lupus.

Other interesting findings included an increased risk of hepatobiliary cancer, especially among men with SLE. Lung cancers were also increased, which has been observed in patients with other autoimmune diseases such as scleroderma and polymyositis. Smoking is a strong predictor for developing autoimmune conditions and may play a role in the observed increased cancer risk.

Early and advanced cardiovascular disease

Patients with SLE are at high risk of atherosclerotic cardiovascular disease. At the University of Pittsburgh Medical Center from 1980 to 1993, we compared the incidence of myocardial infarction in nearly 500 women with SLE and more than 2,000 women of similar age in the Framingham Offspring Study. At ages 15 to 24, women with lupus had a rate of 6.33 per 1,000 person-years; at age 25 to 34, the rate was 3.66 per 1,000 person-years. None of the Framingham women in those age groups had events.

Women ages 35 to 44 with lupus had a risk of heart attack 50 times higher than women in the Framingham cohort, and women in older age groups had a risk 2.5 to 4 times higher.11

Subclinical cardiovascular disease is also increased in women with SLE. Asanuma et al12 used electron-beam computed tomography to screen for coronary artery calcification in 65 patients with SLE and 69 control subjects with no history of coronary artery disease matched for age, sex, and race. Calcification was present in 31% of patients with lupus vs 9% of controls (P = .002). Roman et al13 performed carotid ultrasonography on 197 patients with lupus and 197 matched controls and found more plaque in patients with lupus (37%) than in controls (15%, P < .001).

Other data also suggest that women with lupus have advanced cardiovascular disease and develop it early, with most studies finding the greatest relative risk of cardiovascular disease between ages 18 and 45 years.

Traditional risk factors for cardiovascular disease cannot fully explain the increased risk. Many patients with lupus have metabolic syndrome, hypertension, and renal disease, but even after adjusting for these risk factors, patients with lupus still have about a 7 to 10 times higher risk of nonfatal coronary heart disease and a 17 times higher risk of fatal coronary heart disease.14

Many investigators are now exploring the role of immune dysfunction and inflammation in cardiovascular disease. A number of biomarkers have been proposed for predicting risk of cardiovascular disease in the general population. The list includes many inflammatory factors that rheumatologists have been studying for decades, including myeloperoxidase, autoantibodies, inflammatory cytokines, tumor necrosis factor alpha, and adhesion molecules, many of which also play a role in autoimmunity.

In our patients with SLE, we found that about 90% had three or more modifiable cardiovascular risk factors that were not being addressed appropriately (unpublished data). Lipid management was the least often addressed by rheumatologists and primary caregivers.

There is reason to believe that lupus patients are a high-risk group that merit aggressive risk-factor management, but no formal recommendations can be made without clear evidence that this approach improves outcomes.

SLE INCREASES THE RISK OF ADVERSE PREGNANCY OUTCOMES

Women with SLE more commonly miscarry and deliver low-birth-weight babies than do other women. A history of renal disease is the factor most predictive of poor pregnancy outcome, and the presence of certain autoantibodies increases the risk of neonatal lupus.

We recommend that women with lupus have inactive disease for at least 6 months before becoming pregnant.

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