Overview and Risk Factors
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder of uncertain etiology. Various immune changes occur, including B cell lymphocyte hyperreactivity, T cell lymphocyte defects, complement activation, and autoantibodies to nuclear and cellular antigens.
The clinical course is irregular, with periods of exacerbation and remission, and the severity of disease ranges from mild to life-threatening. Virtually any organ system of the body can be involved, most notably the skin, joints, kidneys, lungs, nervous system, and serous membranes. Organ damage results from deposition of immune complexes within tissues and autoantibody-mediated destruction of host cells. The most common clinical presentations are skin changes, arthritis, and constitutional symptoms (fever, fatigue, weight loss). But more serious manifestations are not uncommon, such as vasculitis (including of the central nervous system), nephritis, pleuritis, pericarditis, arterial and venous thromboses, anemia, leukopenia, and thrombocytopenia.
The prevalence of SLE is 40 to 50 cases per 100,000 people. Incidence has tripled over the past half-century, but this is probably due mostly to improved detection of mild cases.
- Gender. Nearly 90% of cases occur in women, particularly during the childbearing years. The female-to-male ratio is 3:1 in children, approximately 15:1 in adults, and 8:1 in postmenopausal women.
- Ethnicity. African Americans are most commonly affected and are 3 times more likely to have SLE than Caucasians. Hispanic, Asian, and Native Americans also have an increased incidence compared with Caucasians.
- Geography. Prevalence varies significantly by geography. For example, SLE is rare in West Africa, increases in frequency in Central and Southern Africa, and has a high frequency in America and Europe. It is unclear whether this variation is related to environmental or genetic factors.
- Age. Peak onset occurs between 20 and 50 years of age.
- Genetics. There is an increased incidence in close relatives (SLE affects approximately 10% of relatives of index patients) and a strong correlation in monozygotic twins, but specific involved genes have yet to be determined.
- Medications. Development of SLE has been associated with use of hydralazine, isoniazid, methyldopa, and procainamide. However, clinical manifestations of drug-induced SLE tend to be less severe and often remit with removal of the offending agent.
Diagnosis and Treatment
The American College of Rheumatology has established clinical and laboratory criteria to aid in diagnosis. At least 4 of the following 11 criteria should be present for diagnosis:
- Malar rash
- Discoid rash
- Oral or nasopharyngeal ulcers
- Arthritis in more than 2 joints(in 90% of cases)
- Serositis (pleuritis or pleural effusion, pericarditis or pericardial effusion)
- Renal disorders (proteinuria)
- Neurologic disorders (seizure, psychosis)
- Hematologic disorders (anemia, leukopenia, thrombocytopenia)
- Immunologic disorders (anti-DNA antibodies, anti-Smith antibodies, antiphospholipid antibodies, false-positive syphilis serology)
- Antinuclear antibodies (ANA) (in 98% of cases)
Dietary changes, physical activity, smoking cessation, and avoidance of sun exposure are proven nonmedical measures for managing SLE. Pregnancy should be avoided during active disease, due to a high risk of miscarriage and maternal complications. Medical therapy is tailored to specific organ involvement.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in patients with arthritis, myalgias, fever, and mild serositis. However, sulfa-containing NSAIDs (celecoxib) should be used with caution, as they may exacerbate the disease. The risk of adverse events associated with NSAIDs, especially COX-2 inhibitors, should be considered when prescribing these medications.
Steroids are frequently used during exacerbations and are particularly effective for pericarditis, nephritis, cerebritis, and arthritis. It is often wise to seek steroid-sparing therapy so as to mitigate the long-term adverse effects of glucocorticoids. Because long-term steroid use can affect bone structure, dual energy x-ray absortiometry (DEXA) scanning may be helpful to monitor skeletal integrity.
Disease-modifying antirheumatic drugs (azathioprine, hydroxychloroquine, mycophenolate mofetil, cyclophosphamide) may be useful in cases refractory to NSAIDs and/or steroids. In particular, hydroxychloroquine is often beneficial for skin and musculoskeletal symptoms, and mycophenolate mofetil appears to have renal-protective effects. Cyclophosphamide is often used in situations of major organ involvement and life-threatening disease.
Experimental therapies under investigation include stem cell transplantation, anti-B-cell antibodies, other anticytokine antibodies, intravenous immune globulin, and thalidomide.
A number of drugs have reportedly exacerbated the disease or resulted in drug allergy. In particular, sulfonamides should be avoided, as they may exacerbate symptoms. There are also anecdotal reports of aseptic meningitis developing during NSAID use in SLE, such as with ibuprofen.
Measures to protect against direct and indirect sunlight exposure should be emphasized, including daily use of high-SPF sunscreen, wearing long-sleeved shirts and wide-brimmed hats, and avoiding midday sun.
Low-impact, weight-bearing exercise is important for maintaining cardiovascular and bone health in SLE patients.
SLE is one of a number of autoimmune diseases that may be influenced by essential fatty acids, which are precursors of proinflammatory eicosanoids and cytokines. These hormone-like chemicals are a hallmark of disease activity in SLE, and some (thromboxane A2, tumor necrosis factor alpha (TNF α) increase the risk for other inflammatory conditions, including cardiovascular disease, in SLE patients. Although clinical trials have not established a role for diet therapy in preventing or treating SLE, some rationale exists for the use of a low-fat, low-cholesterol diet and a proportionately greater intake of omega-3 fatty acids. The primary nutritional issues are as follows:
Omega-3 fatty acids. Omega-3 fatty acids reduce production of the proinflammatory cytokines (TNF α, interleukin-1) that are implicated in SLE1 by 40% to 60%.2 In patients with lupus nephritis, taking 30 to 45 grams per day of flax seed (a rich source of alpha-linoleic acid) reduced serum creatinine and proteinuria.3,4 Similarly, supplementation with fish oils has been reported to improve disease activity5 and to reduce triglycerides in pediatric SLE patients.6 While these studies suggest that flax oil or other sources of omega-3 fatty acids may be helpful, they included a limited number of participants; their findings require assessment in further studies.
Antioxidants. Poorer antioxidant status is a risk factor for the development of SLE.7 Theoxidative stress that may accompany low antioxidant intake is a frequent finding in, as well as a possible contributor to, SLE and its complications.8,9 Preliminary evidence suggests that antioxidant supplementation using proanthocyanidins may reduce disease activity10 and, with vitamin C and vitamin E, decrease some measures of oxidative stress.11 However, these findings require confirmation in larger controlled trials.
Low-fat, low-cholesterol diet. Patients with SLE frequently have dyslipidemia characterized by elevated triglyceride levels and low high-density lipoprotein (HDL)12 and are at increased risk for cardiovascular events.13 A diet low in saturated fat and cholesterol produced significant reduction in LDL cholesterol in patients with SLE.14 (See Hyperlipidemia.)
Two additional nutritional considerations merit discussion:
Patients with SLE are at risk for glucocorticoid-induced osteoporosis and fractures.15 Limited evidence shows that, at least in pediatric SLE patients, spinal bone density significantly improves with calcium and vitamin D supplementation.16 Adult patients on chronic glucocorticoid therapy should supplement with calcium and vitamin D.
Some evidence suggests that patients benefit from dehydroepiandrosterone (DHEA). At doses of 200 mg/d, DHEA has been found to lower elevated levels of interleukin-6, improve assessments of disease activity, and reduce flares in lupus patients. Some studies have also found steroid-sparing effects and reductions in bone loss with only mild side effects (hirsutism, acne).17,18 However, the potential adverse effects of DHEA on uterine health are not fully elucidated.
Vitamin D and calcium supplementation, as appropriate.
What to Tell the Family
SLE is a serious autoimmune disorder that can be partly treated by lifestyle and nutritional changes. Smoking cessation, avoidance of sun exposure, and regular physical activity are important measures. Supplementation with omega-3 fatty acids may decrease the activity of the disease and, especially in conjunction with a low-fat, low-cholesterol diet, protect the heart. Patients using chronic steroid therapy are at risk for osteoporosis. These patients should have their bone density checked on a regular basis and should supplement their diets with calcium and vitamin D.
1. Aringer M, Smolen JS. Tumor necrosis factor and other pro-inflammatory cytokines in systemic lupus erythematosus: a rationale for therapeutic intervention. Lupus. 2004;13:344-347.
2. Kettler DB. Can manipulation of the ratios of essential fatty acids slow the rapid rate of postmenopausal bone loss? Altern Med Rev. 2001;6:61-77.
3. Clark WF, Kortas C, Heidenheim AP, Garland J, Spanner E, Parbtani A. Flaxseed in lupus nephritis: a two-year nonplacebo-controlled crossover study.
J Am Coll Nutr. 2001;20:143-148.
4. Clark WF, Parbtani A, Huff MW, et al. Flaxseed: a potential treatment for lupus nephritis. Kidney Int. 1995;48:475-480.
5. Walton AJ, Snaith ML, Locniskar M, Cumberland AG, Morrow WJ, Isenberg DA. Dietary fish oil and the severity of symptoms in patients with systemic lupus erythematosus. Ann Rheum Dis. 1991;50:463-466.
6. Ilowite NT, Copperman N, Leicht T, Kwong T, Jacobson MS. Effects of dietary modification and fish oil supplementation on dyslipoproteinemia in pediatric systemic lupus erythematosus. J Rheumatol. 1995;22:1347-1351.
7. Comstock GW, Burke AE, Hoffman SC, et al. Serum concentrations of alpha tocopherol, beta-carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis. 1997;56:323-325.
8. Alves JD, Grima B. Oxidative stress in systemic lupus erythematosus and antiphospholipid syndrome: a gateway to atherosclerosis. Curr Rheumatol Rep. 2003;5:383-390.
9. Kovacic P, Jacintho JD. Systemic lupus erythematosus and other autoimmune diseases from endogenous and exogenous agents: unifying theme of oxidative stress. Mini Rev Med Chem. 2003;3:568-575.
10. Stefanescu M, Matache C, Onu A, et al. Pycnogenol efficacy in the treatment of systemic lupus erythematosus patients. Phytother Res. 2001;15:698-704.
11. Tam LS, Li EK, Leung VY, et al. Effects of vitamins C and E on oxidative stress markers and endothelial function in patients with systemic lupus erythematosus: a double-blind, placebo-controlled pilot study. J Rheumatol. 2005;32:275-282.
12. Svenungsson E, Gunnarsson I, Fei GZ, Lundberg IE, Klareskog L, Frostegard J. Elevated triglycerides and low levels of high-density lipoprotein as markers of disease activity in association with up-regulation of the tumor necrosis factor alpha/tumor necrosis factor receptor system in systemic lupus erythematosus. Arthritis Rheum. 2003;48:2533-2540.
13. Bessant R, Hingorani A, Patel L, MacGregor A, Isenberg DA, Rahman A. Risk of coronary heart disease and stroke in a large British cohort of patients with systemic lupus erythematosus. Rheumatology (Oxford). 2004;43:924-929.
14. Shah M, Coyle Y, Kavanaugh A, Adams-Huet B, Lipsky PE. Development and initial evaluation of a culturally sensitive cholesterol-lowering diet program for Mexican and African American patients with systemic lupus erythematosus.
Arthritis Care Res. 2000;13:205-212.
15. Di Munno O, Mazzantini M, Delle Sedie A, Mosca M, Bombardieri S. Risk factors for osteoporosis in female patients with systemic lupus erythematosus. Lupus. 2004;13:724-730.
16. Warady BD, Lindsley CB, Robinson FG, Lukert BP. Effects of nutritional supplementation on bone mineral status of children with rheumatic diseases receiving corticosteroid therapy. J Rheumatol. 1994;21:530-535.
17. Petri MA, Mease PJ, Merrill JT, et al. Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus. Arthritis Rheum. 2004;50:2858-2868.
18. Chang DM, Lan JL, Lin HY, Luo SF. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002;46:2924-2927.