Systemic Lupus Erythematosus
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, 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 (e.g., fever, fatigue, weight loss, muscle aches). More serious manifestations are not uncommon and can include vasculitis (often affecting the central nervous system), nephritis, pleuritis, pericarditis, arterial and venous thromboses, anemia, leukopenia, and thrombocytopenia.
In the United States, the prevalence of SLE is approximately 50 cases per 100,000 people. The incidence has tripled over the second half of the past century; some of these cases have been attributed 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.
Race and Ethnicity. African Americans are most commonly affected and are often diagnosed at a younger age, compared with American whites. They are 3-4 times more likely to have SLE compared to whites. Hispanic, Asian, and Native Americans also have an increased prevalence compared to whites.
Geography. Prevalence varies significantly by geography. 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. Multiple genetic defects have been discovered which increase risk of developing SLE. These genes have been associated a variety of immune system functions.
Medications. Development of an SLE-like syndrome has been associated with use of many different medications. Some of the more notable drugs associated with this syndrome are: hydralazine, isoniazid, methyldopa, diltiazem, and procainamide. Biological agents used in treating rheumatic diseases have also been implicated. Clinical manifestations of drug-induced SLE tend to be less severe and often remit with removal of the offending agent.
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)
*Exceptions can be made based on clinical suspicion, and in these cases, the diagnosis may be made with fewer than four criteria.
Lupus flares are characterized by an acute worsening of any of the above listed criteria. Often these flares are also associated with increased serologic disease activity. Flares range from mild to severe.
Once the diagnosis of lupus is established, treatment should be initiated with the goal of halting disease progression and minimizing flares. Active disease is equated with disease progression, which leads to worse long-term outcomes.
Dietary changes, physical activity, smoking cessation, and avoidance of sun exposure are helpful SLE. , , Low-impact, weight-bearing exercise is important for maintaining cardiovascular and bone health.
In pregnant women with active disease, there is a high risk of miscarriage and maternal complications. In addition, some pharmaceutical therapies for lupus are incompatible with pregnancy.
Influenza vaccine is safe for SLE patients but is less effective than for other individuals.
Nonsteroidal antiinflammatory drugs (NSAIDs) are used in patients with arthritis, myalgias, fever, and mild serositis. However, sulfa-containing NSAIDs (celecoxib) and antibiotics 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 flares and are particularly effective for pericarditis, nephritis, cerebritis, and arthritis. However, steroid-sparing therapy using disease-modifying antirheumatic drugs (see below) are preferred over glucocorticoids since they do not have the long-term adverse effects. Among other serious adverse effects, long-term steroid use can reduce bone density, therefore dual energy x-ray absortiometry (DEXA) scanning is recommended for anyone who is beginning chronic steroids or has been maintained on steroids for more than three months.
Disease-modifying antirheumatic drugs (azathioprine, hydroxychloroquine, mycophenolate mofetil, cyclophosphamide, etc.) are preferred over chronic steroids. The antimalarial medication hydroxychloroquine is often used as a first-line medication to reduce incidence of flares. It has been in use for many decades and is well tolerated. Retinal toxicity is rare but annual ophthalmologic examinations are recommended in current guidelines. Mycophenolate mofetil appears to have renal-protective effects. Cyclophosphamide is often used in situations of major organ involvement and life-threatening disease.
Biological agents are used for certain manifestations of moderate to severe lupus. These agents are typically monoclonal antibodies which regulate functions associated with B and T cells. Patients must be carefully monitored for adverse events.
Treatment of SLE flares can range from increasing current doses of prescriptions for mild flares to hospitalization with IV steroid and/or immunosuppression administration for severe flares.
SLE patients have greater risk for cardiovascular and kidney diseases than healthy individuals do. As a result of disturbances in serum lipids, inflammation, and oxidative stress, SLE patients need to follow a diet that addresses these factors. The primary nutritional issues include the maintenance or attainment of healthy weight following a healthful diet that helps reduce serum lipids and provides high amounts of nutritional antioxidants, and are described as follows:
Attainment of a healthy weight. Obesity is associated with elevated serum lipids and other cardiovascular risk factors that are well known to be present in SLE patients. Obese women with SLE had higher disability ratings and significantly lower scores on tests of functional capacity when compared with non-obese SLE patients. Obesity also causes oxidative stress, which underlies pathological processes seen in SLE.
A low-saturated-fat, low-cholesterol diet. Patients with SLE frequently have dyslipidemia characterized by elevated triglyceride levels and low high-density lipoprotein (HDL) and are at increased risk for cardiovascular events. One study also found that patients with SLE consume significantly more refined carbohydrates, less fiber, and lower amounts of omega-3 fatty acids than healthy controls, which can further increase cardiovascular risk. In recognition of these facts, an American Heart Association Expert Panel provided recommendations for prevention and treatment of cardiovascular risk for pediatric patients with SLE, including evaluation and education by nutrition professionals. Diet education for individuals with SLE and dyslipidemia should include meals low in saturated fat and cholesterol, and evidence indicates that such treatment produces significant reduction in LDL cholesterol in patients with SLE. (See Dyslipidemias chapter.)
There are also reasons to suggest the proper diet for SLE patients should be free of or low in animal products. Apart from being the only source of dietary cholesterol and the chief source of saturated fat, abundant supplies of amino acids (such as are found in animal protein) activate the mammalian target of rapamycin (mTOR). , This pathway is activated in SLE patients, and its blockade by either rapamycin or N-acetylcysteine results in clinical improvement in these patients. The effectiveness of certain other dietary supplements in SLE patients (described below) is also contingent upon suppression of mTOR.
Omega-3 fatty acids. Controlled clinical trials of fish oil supplementation in SLE patients have found significant reductions in Systemic Lupus Activity Measurement – Revised (SLAM-R) scores proteinuria and triglycerides. Neither plant sources of the parent omega-3 fatty acid alpha linolenic acid nor botanical sources of DHA have been tested for benefits in SLE patients.
Antioxidants. Excess production of reactive oxygen species (‘free radicals’) and a reduction in antioxidant defenses, together known as ‘oxidative stress’, are implicated in the development of SLE. An excess production of oxygen radicals triggers both autoreactivity towards self-antigens and a shift from anti- to proinflammatory cytokine production.
Elevated levels of oxidative stress are linked to poor clinical outcomes, including more aggressive and prolonged need for medications, development of cardiovascular risk factors (early atherosclerosis, insulin-resistance, hypertension), proteinuria, liver damage, and increases in the SLE disease activity index. A specific deficit of the antioxidant glutathione (GSH) exists, and is a known cause of T-cell dysfunction in SLE. Supplementing SLE patients with the glutathione precursor N-acetylcysteine (NAC) blocks mTOR activation and significantly improves disease activity in SLE patients by enhancing T-cell apoptosis and reducing reducing autoantibody production. Several other case reports have established the benefit of NAC treatment in SLE patients, , and additional clinical trials are needed to verify these results.
Adequate vitamin D status. A systematic review of vitamin D studies in SLE found that 10 out of 15 investigations revealed a significant inverse relationship between vitamin D levels and disease activity. Results of studies of vitamin D supplementation in SLE patients have so far been equivocal with regard to reduced disease activity and changes in immunologic parameters. Limited evidence shows that, at least in pediatric SLE patients, spinal bone density significantly improves with combined vitamin D and calcium supplementation. Due to the fact that patients with SLE are at risk for glucocorticoid-induced osteoporosis and fractures, supplementation with calcium and vitamin D should be considered.
Moderate alcohol consumption. A meta-analysis concluded that compared with no consumption, moderate alcohol consumption was associated with a significantly decreased risk for SLE, possibly through the inhibition of interleukin-6 (IL-6) production or other proinflammatory cytokines.
Turmeric supplementation. A small controlled clinical trial in which SLE patients were supplemented with 500 mg. turmeric spice three times daily found significant decreases in proteinuria, systolic blood pressure, and hematuria in the active treatment group. Additional studies are needed to confirm these benefits.
Glucocorticoids also increase the risk for diabetes, thereby increasing cardiovascular risk for SLE patients. Although this risk is decreased by disease-modifying anti-rheumatic drugs, no evidence suggests that dietary treatment can prevent the development of insulin resistance in steroid-treated SLE patients.
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.
For patients who continue to have symptoms or serious flares, recent advances in pharmacotherapy have improved quality of life, compared with the use of steroids. Patients using chronic steroid therapy are at risk for osteoporosis. It is recommended to avoid or taper off steroid use when at all possible. These patients should have their bone density checked on a regular basis and should supplement their diets with calcium-rich foods and vitamin D.
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