Minimizing Adverse Outcomes Of Therapies And Long-term Disease
Several strategies are useful for minimizing adverse outcomes related to glucocorticoid and cytotoxic therapies 41, 82, 83, 84, 85 as summarized in Table 76-7. Patients should be monitored frequently for signs of infection, and appropriate antimicrobial agents should be prescribed as soon as infection is suspected, then changed or discontinued as results of cultures become available. Infections with opportunistic organisms are common in immunosuppressed patients with SLE 42, 43 ; special procedures may be required to identify these organisms. For example, diagnosis of Pneumocystis infection, invasive Candida infection, aspergillosis, mycobacterial disease, and viruses such as cytomegalovirus may require biopsy of the affected organs. Immunization of SLE patients with influenza and pneumococcal vaccines (and probably with most other vaccines) is safe and usually effective, 82 although patients who receive high doses of immunosuppressive drugs may make inadequate protective-antibody responses.
Careful attention to blood pressure control and correction of hypokalemia and symptomatic hyperglycemia are recommended for patients receiving glucocorticoids. Frequent monitoring for adverse effects on bone marrow, liver, and lung are recommended for patients receiving cytotoxic drugs.
Osteoporosis can be a serious problem (overall prevalence of approximately 15 percent in SLE patients) in glucocorticoid-treated patients, especially in individuals who are Caucasian, postmenopausal, older than 50 years, and those with a high cumulative dose of glucocorticoids. 83, 84, 85, 86 Several strategies help maintain bone mass in such individuals. 83, 84 These strategies include calcium supplementation to achieve a total daily intake of 1000 to 1500 mg, plus 50,000 units vitamin D one to three times a week, or daily calcitriol in patients with low urinary calcium (below 120 mg in 24 hours). In addition, estrogen replacement therapy in menopausal women, progesterone, androgens, calcitonin, and bisphosphonates have all been shown to stabilize bone mass in patients on glucocorticoid therapy. Administration of estrogen to patients with SLE is controversial for several reasons. First, there is a possibility that disease might be aggravated by female sex hormones. Studies of a large cohort of nurses showed a higher incidence of SLE in women who had ever received oral contraceptives or estrogen replacement therapy compared to women without such therapies. 87, 88 A prospective, randomized controlled trial addressing the safety of estrogen therapies in women with SLE has been completed 88a and shows a higher rate of mild but not severe disease flares in women on hormone replacement therapy (estrogen plus progesterone) compared to placebo. Secondly, recent studies have shown that administration of estrogen/progesterone combinations to healthy postmenopausal women increases the risk for myocardial infarction and stroke, as well as previously known increases in venous thromboses and breast cancer. 89 Because morbidity and mortality from atherosclerosis, including myocardial infarcts and strokes, are increased in women with SLE, particularly after a decade of disease, hormone replacement therapy that includes estrogen and progesterone may do harm in some. Virtually all data support the benefit of estrogen replacement for preventing osteoporosis, so the physician must decide which risk is greater. To prevent osteoporosis, use of calcium, adequate vitamin D, and bisphosphonates seems the safest choice at the time of this writing.
Atherosclerosis is accelerated in some patients with SLE: The overall risk for symptomatic atherosclerosis may be increased as much as 50-fold in women with SLE between the ages of 35 and 44. 90, 91 In women with SLE older than 40, the relative risk for myocardial infarction is approximately 10. 91, 91a, 91b Predisposing factors include hypertension, increasing age, increasing disease duration, and hyperlipidemia. 91, 92 One study 91a showed that SLE patients with carotid plaque compared to those without had lower mean daily doses of prednisone and less use of cytotoxics, suggesting that more aggressive control of SLE disease activity might decrease the accleration of atherosclerosis. Therefore, the physician must pay close attention to control of all treatable risk factors predisposing to this complication. There is interest in considering statin therapies in SLE, 93, 94 not only for their abilities to decrease risk for myocardial infarction and to lower levels of total cholesterol and low-density lipoproteins, but also because they may have anti-inflammatory effects. Data are available showing that postmenopausal women with preexisting heart disease, receiving estrogen and progesterone, are protected from increased risk for myocardial infarction if they are receiving statin therapies. 93 There are no prospective data published as yet in patients with SLE; such a study is in progress.
Print
Email
