eMedicine Specialties > Rheumatology > Systemic Rheumatic Disease
Systemic Lupus Erythematosus: Treatment & Medication
Updated: Jan 22, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Management for systemic lupus erythematosus (SLE) depends on disease severity. Periodic follow-up and laboratory testing, including urinalyses, CBC count with differential, and creatinine, are imperative to detect signs and symptoms of new organ-system involvement and to monitor the response or adverse reactions to therapies. At least quarterly visits are recommended in most cases. The European League Against Rheumatism (EULAR) recently released new recommendations for the treatment of SLE.
Treatment recommendations for SLE depend on disease manifestations.24 In general, fever, cutaneous manifestations, musculoskeletal manifestations, and serositis represent milder disease, which may wax and wane with disease activity. These are often controlled with low-potency medications or short steroid courses. CNS involvement and renal disease must be recognized as more severe disease manifestations and are often treated with more aggressive immunosuppression.
Acute emergencies in SLE include severe neurologic involvement, systemic vasculitis, profound thrombocytopenia with a TTP-like syndrome, rapidly progressive glomerulonephritis, and diffuse alveolar hemorrhage. These may be treated with high-dose intravenous steroids and cytotoxic therapy such as cyclophosphamide. In rare cases, TTP, diffuse alveolar hemorrhage, or profound steroid-refractory thrombocytopenia may require plasma exchange or therapy with intravenous immunoglobulin (IVIG), respectively. Catastrophic antiphospholipid antibody syndrome also requires aggressive acute management. (See the article Antiphospholipid Syndrome in eMedicine’s Rheumatology volume for more details.)
Preventative care measures for patient with SLE are necessary to minimize the risks of steroid-induced osteoporosis and accelerated atherosclerotic disease. The ACR Guidelines for the prevention of glucocorticoid-induced osteoporosis suggest traditional steps and the consideration of prophylactic bisphosphonate therapy. Recently, numerous authors have also advocated drafting cardiovascular prevention guidelines that equate SLE as a "CAD risk-equivalent" similar to diabetes mellitus. This is based on a 10-year coronary event rate of 13-15% in patients with active SLE compared with a 10-year event rate of 18.8% in patients with known CAD.25
Consultations
The multisystemic nature of SLE often requires involvement of consultants, depending on the organ system involved. Consultation with any of the following specialists may be necessary:
- Rheumatologist
- Infectious disease specialist
- Neurologist
- Pulmonologist
- Cardiologist
- Gastroenterologist
- Nephrologist
- Dermatologist
- Hematologist
Diet
No diet-based treatment of SLE has been proven effective.
Activity
Patients with SLE should be reminded that activity may need to be modified as tolerated. Specifically, stress such as physical illness may precipitate SLE flares. Additionally, persons with SLE should wear sunscreen and protective clothing or avoid sun exposure to limit photosensitive rash or disease flares.
Medication
Treatment of systemic lupus erythematosus (SLE) is guided by the individual patient's manifestations. Fever, rash, musculoskeletal manifestations, and serositis generally respond to treatment with hydroxychloroquine, NSAIDS, and low-to-moderate–dose steroids, as necessary, for acute flares. Medications such as methotrexate may be useful in chronic lupus arthritis, and azathioprine and mycophenolate have been widely used in moderate severity lupus.
CNS involvement and renal disease constitute more serious disease and often require high-dose steroids and other immunosuppression agents such as cyclophosphamide, azathioprine, or mycophenolate. Class IV diffuse proliferative lupus nephritis has also been treated with aggressive cyclophosphamide induction therapy, and recent trials of mycophenolate have not demonstrated superiority.26 New investigations are in progress to examine the role of rituximab and other biological therapies in SLE. Recent observational evidence suggests that hydroxychloroquine may have protective benefits in patients with SLE, including improved survival.27
Nonsteroidal anti-inflammatory drugs (NSAIDs)
These agents provide symptomatic relief for arthralgias, fever, and mild serositis.
NSAIDs may cause elevated liver function test results in patients with active SLE. Additionally, concomitant administration with prednisone may increase risk of GI ulceration.
Ibuprofen (Advil, Motrin, Ibuprin)
DOC for patients with mild-to-moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis
Adult
400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist; not to exceed 2.4 g/d
Pediatric
20-70 mg/kg/d PO divided tid/qid, start at lower end of dosing range and titrate; not to exceed 2.4 g/d
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy; can cause aseptic meningitis in SLE
Antimalarials
Antimalarials may work through numerous proposed mechanisms in SLE, mediating subtle immunomodulation without overt immunosuppression. They are useful in preventing and treating lupus skin rashes, constitutional symptoms, arthralgias, and arthritis. They also help to prevent lupus flares and have been associated with reduced morbidity and mortality in SLE.
Hydroxychloroquine (Plaquenil)
Inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.
Adult
200 mg PO qd/bid; if BW <130 lb, may be candidate for dose reduction to qd to minimize retinal toxicity
Pediatric
3-5 mg/kg/d (base) PO qd or divided bid; not to exceed 6.5 mg/kg/d adult dose
Serum levels increase with cimetidine; magnesium trisilicate may decrease absorption
Documented hypersensitivity; psoriasis; retinal and visual field changes that limit monitoring
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; not recommended for long-term use in children; refer for maintenance ophthalmologic examinations; test periodically for muscle weakness
Immunosuppressant agents
These agents act as immunosuppressives and cytotoxic and anti-inflammatory agents.
Methotrexate (Folex PFS, Rheumatrex)
For managing arthritis, serositis, cutaneous, and constitutional symptoms. Blocks purine synthesis and AICAR, thus increasing anti-inflammatory adenosine concentration at sites of inflammation. Ameliorates symptoms of inflammation.
Adult
7.5-25 mg PO/IM qwk
Pediatric
Not established
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate (MTX); charcoal lowers MTX levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX; coadministration with NSAIDs may (rarely) be fatal only in high-dose MTX; indomethacin and phenylbutazone can increase MTX plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity of MTX; may increase plasma levels of thiopurines
Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
Pregnancy
D - Unsafe in pregnancy
Precautions
Monitor CBC counts monthly and liver and renal function q2mo during therapy (monitor monthly during initial 6 mo, with dose adjustments, or upon risk of elevated MTX levels); MTX has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if blood counts drop significantly; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly with MTX (possibility of increased toxicity with NSAIDs, including salicylates, has not been noted at rheumatologic dosing levels)
Cyclophosphamide (Cytoxan)
Used for immunosuppression in cases of serious SLE organ involvement, especially severe CNS involvement, vasculitis, and lupus nephritis. Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Adult
500-750 mg/m2 IV qmo
Pediatric
Administer as in adults
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Unsafe in pregnancy
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis, monitoring should continue at least annually indefinitely after treatment; infertility is a common complication that should be disclosed (ovulatory suppression or egg/sperm harvest may be discussed prior to treatment)
Azathioprine (Imuran)
Immunosuppressant and less toxic alternative to cyclophosphamide and as steroid-sparing agent in nonrenal disease. Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.
Adult
1 mg/kg/d PO for 6-8 wk, increase by 0.5 mg/kg q4wk until response or until dose reaches 2.5 mg/kg/d
Pediatric
Not established
Allopurinol inhibits xanthine oxidase and raises levels of azathioprine to potentiate toxicity; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT)
Pregnancy
D - Unsafe in pregnancy
Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; consider assessing TPMT level prior to therapy; monitor liver, renal, and hematologic function monthly; pancreatitis rarely associated
Immune globulin intravenous (Gamimune, Gammagard, Sandoglobulin)
Used for immunosuppression in serious SLE flares. Neutralizes circulating myelin antibodies through anti-idiotypic antibodies. Down-regulates proinflammatory cytokines, including INF-gamma. Blocks Fc receptors on macrophages, suppresses inducer T and B cells, and augments suppressor T cells. Blocks complement cascade, promotes remyelination, and may increase CSF IgG (10%).
Adult
2 g/kg IV over 2-5 d
Pediatric
Not established
Increases toxicity of live virus vaccine (MMR); do not administer within 3 mo of vaccine
Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-5 d postinfusion to 30 d); increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; laboratory result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia
Mycophenolate (CellCept)
Useful for maintenance in lupus nephritis and other serious lupus cases. Inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production.
Adult
Titrate to 1 g PO bid
Pediatric
Not established; 15-23 mg/kg PO bid suggested
In combination with either acyclovir or ganciclovir, may result in higher levels for both interacting drugs because of competition for renal tubular excretion; aluminum/magnesium in some antacids and cholestyramine-containing products may decrease absorption, reducing levels (do not administer together); probenecid may increase levels of mycophenolate; salicylates and azathioprine may increase toxicity; may decrease levonorgestrel AUC; may decrease live virus vaccine immune response; may increase free fraction levels of theophylline when administered with theophylline
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk for infection (monitor blood count); severe renal impairment (CrCl <25 mL/min) may have increased adverse effects due to increase free MPA; caution in active peptic ulcer disease; incidence of malignancies and lymphoma consistent with that reported for other immunosuppressants (0.9%); commonly causes constipation, nausea, diarrhea, urinary tract infection, and nasopharyngitis; rare reports include interstitial lung disorders, colitis, pancreatitis, intestinal perforation, GI hemorrhage, gastric ulcers, duodenal ulcers, and ileus; do not chew, crush, or cut Myfortic tab
Corticosteroids
These agents are used predominately for anti-inflammatory activity and as immunosuppressants. Preparations include oral, intravenous, topical, and intraarticular injections.
Methylprednisolone (Adlone, Medrol, Solu-Medrol, Depopred)
Used for acute organ-threatening exacerbations. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
1 g/d IV for 3 d
Pediatric
Not established
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use
Prednisone (Deltasone, Orasone, Meticorten)
Immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. Low-dose oral prednisone can be used for milder SLE, but more severe involvement necessitates high doses of oral or intravenous therapy
Adult
5-60 mg/d PO qd or divided bid/qid; taper over week(s) as symptoms resolve
Pediatric
4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
More on Systemic Lupus Erythematosus |
| Overview: Systemic Lupus Erythematosus |
| Differential Diagnoses & Workup: Systemic Lupus Erythematosus |
 Treatment & Medication: Systemic Lupus Erythematosus |
| Follow-up: Systemic Lupus Erythematosus |
| Multimedia: Systemic Lupus Erythematosus |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
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[Best Evidence] Petri M, Kim MY, Kalunian KC, Grossman J, Hahn BH, Sammaritano LR. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med. Dec 15 2005;353(24):2550-8. [Medline].
Further Reading
Additional resources on system lupus erythematosus (SLE) are available at Medscape's Lupus Resource Center.
Keywords
systemic lupus erythematosus, SLE, lupus, systemic lupus, multisystem inflammatory disease, autoimmune disorder, chronic autoimmune disease, multisystem microvascular inflammation, nephritis, severe systemic vasculitis, malar rash, discoid rash, photosensitivity, Jaccoud arthropathy, butterfly rash, discoid lupus, lupus profundus, vasculitic purpura, microangiopathic lupus cerebritis, renal lupus, CNS lupus, lupus pneumonitis, chronic lupus interstitial lung disease, lupus disease, lupus peritonitis, drug-induced lupus erythematosus, neonatal lupus, lupus nephritis, lupus skin rash, lupus arthritis, lupus flare
