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Lupus Erythematosus, Acute: Treatment & Medication
Updated: Jul 15, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Systemic corticosteroids (prednisone 0.5-1 mg/kg/d) usually are the mainstay of therapy for systemic disease. Skin changes tend to respond in tandem with the systemic response to treatment. A rheumatologist usually undertakes systemic treatment. When administering systemic corticosteroids, address adverse effects such as diabetes mellitus, hypertension, osteonecrosis, the stigmata of Cushing syndrome, and the risk of osteoporosis.
- Perform a baseline bone densitometry scan, and if normal, repeat the scan at 6 months.
- Ideally, perform 24-hour urine collection to check calcium levels, since steroids enhance renal excretion of calcium, thereby increasing the patient's susceptibility to developing renal stones. If the results are normal, administer cholecalciferol (400-800 IU/d) and calcium (1500 mg/d).
- If evidence of hypercalciuria is present, administer thiazide diuretics until levels return to normal.
- If osteoporosis is present, refer the patient to an osteoporosis specialist for consideration of treatment with bisphosphonates.
- Additional immunosuppressive agents, such as azathioprine (0.5-3 mg/kg/d), cyclophosphamide (1-5 mg/kg/d, typically 50-200 mg/d), and thalidomide (100-200 mg/d), are used as adjuvant therapy to treat systemic disease because of steroid-sparing effects.
- Hydroxychloroquine also has been shown to have steroid-sparing effects and is administered as first-line therapy to most patients with systemic disease. The effects of hydroxychloroquine on skin lesions are especially beneficial.
- Intravenous IgG (IVIG; 0.5-1 g/kg/d for 4 d) has become important in controlling recalcitrant disease.5
- Mycophenolate mofetil has shown poor results in disease refractory to multiple treatment modalities.6
- One case reports describes the effectiveness of plasmapheresis for refractory toxic epidermal necrolysis (TEN)–like acute cutaneous lupus erythematosus.7
Consultations
- Refer patients with clinical and serologic evidence of lupus erythematosus to a rheumatologist for further treatment.
- Refer patients with red blood cell casts, significant proteinuria (>0.5 g/mL/24h), and a diastolic blood pressure of more than 90 mm Hg to a nephrologist.
Diet
Dietary restrictions may be necessary in the presence of renal compromise.
Activity
Advise patients to avoid activities involving excessive exposure to the sun.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Belimumab is investigational. It is a neutralizing B-lymphocyte stimulator monoclonal antibody that inhibits the biologic activity of the soluble form of essential B cells. Belimumab is currently undergoing phase III clinical trials for the potential treatment of systemic lupus erythematosus (SLE). Doses used in the phase II trials were randomized to 1, 4, or 10 mg/kg intravenously on days 1, 14, and 28, and then every 28 days for 76 weeks. The treatment significantly improved the SLE disease activity index (SLEDAI) scores in seropositive patients (ANA ≥1:80 or anti-dsDNA >30 IU) and physicians global assessment score.8
Epratuzumab is investigational. It is a humanized anti-CD22 monoclonal antibody that partially depletes B cells. Treatment is shown to decrease disease activity but not autoantibody levels in patients with moderately active systemic lupus erythematosus. In an open-label, single-case study of 14 patients with systemic lupus erythematosus, patients received intravenous epratuzumab at 360 mg/m2 every 2 weeks for 4 doses, with analgesic/antihistamine premedication prior to each dose. Total British Isle Lupus Assessment Group (BILAG) scores were decreased by greater than or equal to 50% in all 14 patients at 6 weeks.
Corticosteroids
Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisone (Deltasone, Meticorten, Orasone, Sterapred)
Glucocorticoid (adrenocortical steroid) absorbed easily into GI tract. Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production.
Adult
0.5-1 mg/kg/d PO prn for short periods
Pediatric
Administer as in adults
Ketoconazole, erythromycin, clarithromycin, estrogens, birth control pills increase levels; aminoglutethimide, phenytoin, phenobarbital, rifampin, cholestyramine, and ephedrine decrease levels
Levels of potassium-depleting diuretics (potentiates potassium loss and digitalis toxicity) and cyclosporine may increase; levels of isoniazid, insulin (resistance is induced), and salicylates may decrease
Monitor anticoagulant therapy and theophylline levels
Absolute: Systemic fungal infection; herpes simplex keratitis; hypersensitivity (usually with corticotropin, occasionally with IV preparations)
Relative: Hypertension; active TB ; congestive heart failure; prior psychosis; positive IPPD test result; glaucoma; severe depression; diabetes mellitus; active peptic ulcer disease; cataracts; osteoporosis; recent bowel anastomosis; pregnancy.
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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.
Use lower dose in hypothyroidism, liver disease, and obesity (conditions decrease cortisol-binding globulin and increase free fraction of steroid); pregnancy, hyperthyroidism, and concurrent estrogen therapy may increase cortisol-binding globulin level
Immunosuppressives
Used for immunosuppression and, ultimately, for disease control.
Azathioprine (Imuran)
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity. For dermatomyositis/polymyositis, respiratory and muscular symptoms respond but skin lesion response has not been consistent.
Slow acting with therapeutic effect not seen for 6-8 wk. Metabolites accumulate slowly, and maximal immunosuppression not reached until 8-12 wk. Available as 25-, 50-, 75-, and 100-mg tab or 100-mg vial.
Adult
1 mg/kg/d qd or bid (empiric) or by TPMT level (see Precautions); increase dose by 0.5 mg/kg/d after 6-8 wk prn; increase q4wk, not to exceed 2 mg/kg/d for most dermatologic purposes
Pediatric
Initial: 2-5 mg/kg/d PO/IV
Maintenance: 1-2 mg/kg/d PO/IV
Allopurinol increases risk of pancytopenia; captopril/ACE inhibitors may increase risk of anemia and leukopenia; increased dose of warfarin may be necessary; may need increased dose of pancuronium for adequate paralysis; live-virus vaccines, co-trimoxazole (increased risk of hematologic toxicity); rifampicin (transplants possibly rejected); clozapine (increased risk of agranulocytosis)
Absolute: Documented hypersensitivity, pregnancy or attempting pregnancy, and clinically significant active infection
Relative: Concurrent use of allopurinol; prior treatment with alkylating agents (cyclophosphamide, chlorambucil, melphalan, others) (high risk of neoplasia)
Pediatric: Safety and efficacy in not established
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
TPMT testing not entirely reliable; it involves testing TPMT activity in RBCs, which correlates with systemic TPMT activity; functional enzyme test shown to have variability between test sites, and kits may contain varying amounts of enzyme inhibitor; starting at low doses, monitoring for pancytopenia, and then increasing dose is alternative; if clinical response is not good, patient may be a homozygote for high activity and may need an increased dose
Possible increased risk of lymphoproliferative disorders with long-term therapy; increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur
Dosing by TPMT
TPMT <5 U: No treatment with azathioprine
TPMT 5-13.7 U: Up to 0.5 mg/kg/d
TPMT 13.7- 19 U: Up to 1.5 mg/kg/d
TPMT >19 U: Up to 2.5 mg/kg/d
Cyclophosphamide (Cytoxan, Neosar)
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 - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis
Thalidomide (Thalomid)
Immunomodulatory agent that may suppress excessive production of tumor necrosis factor-alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration.
In patients <50 kg (110 lb), start at low end of dose regimen.
Adult
100-300 mg/d PO qd with water, preferably hs and at least 1 h pc
Pediatric
Not established
May increase sedation of alcohol, barbiturates, chlorpromazine, and reserpine; women must use 2 additional methods of contraception or abstain from intercourse because of teratogenic effects
Documented hypersensitivity
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Perform pregnancy test within 24-h period prior to initiating therapy (weekly during first month, followed by monthly tests in women with regular menstrual cycles or q2wk with irregular menstrual cycles); bradycardia may occur; use protective measures (eg, sunscreens, protective clothing) against exposure to sunlight or UV light (eg, tanning beds); prescribing physician must register with STEPS provider registry established by manufacturer
Hydroxychloroquine (Plaquenil)
Inhibits chemotaxis of eosinophils, 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
310 mg PO qd or bid for several wk depending on response; 155-310 mg/d for prolonged maintenance therapy
Pediatric
3-5 mg base/kg/d PO qd or divided bid; not to exceed 7 mg/kg/d
Serum levels increase with cimetidine; magnesium trisilicate may decrease absorption; may increase digoxin levels; do not give with chloroquine due to increased retinal toxicity
Absolute: Hypersensitivity, retinopathy from any cause
Relative: Pregnancy/lactation; retinal/visual-field change; severe blood dyscrasias; psoriasis; G-6-PD deficiency; significant hepatic dysfunction; myasthenia gravis; significant neurologic disease; long-term therapy in children
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; not recommended for long-term use in children; perform periodic (6 mo) ophthalmologic examinations; test periodically for muscle weakness
Immune globulin IV (Sandoglobulin, Gammagard, Gamimune, Gammar-P)
Neutralize 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; may increase CSF IgG (10%).
Adult
2g/kg IV over 10-12 h
Gammagard S/D: 1 g/kg as single dose or 400 mg/kg for 4 consecutive days beginning within 7 d of fever onset; administration concomitantly with appropriate aspirin therapy (80-100 mg/kg/d divided qid) recommended
Pediatric
Not established
Antibodies in globulin preparation may interfere with response to live viral vaccines (eg, MMR); defer using live viral vaccines until approximately 11 mo after immunoglobulin administration; no known drug interactions
No absolute contraindication other than documented hypersensitivity; patients who are IgA deficient should receive IVIG preparations with no IgA; anti-IgE/IgG antibodies, severe thrombocytopenia, or coagulation disorders
Gammagard S/D contains only trace amounts of IgA and is not indicated in patients with selective IgA deficiency in whom the IgA deficiency is the only abnormality of concern and it should be given with caution to patients with antibodies to IgA or IgA deficiencies that are a component of an underlying primary immunodeficiency disease for which IVIG therapy is indicated; in such instances, a risk of anaphylaxis may exist despite the fact that Gammagard S/D contains only trace amounts of IgA
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Check serum IgA level 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 (2-30 d postinfusion); 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
Monoclonal Antibody
Rituximab (Rituxan)
Murine/human chimeric anti-CD20 monoclonal antibody. CD20 is expressed early in pre-B cell development. Binding induces complement-dependent B-cell cytotoxicity along with antibody-dependent cellular toxicity.
Adult
375 mg/m2 qwk for 4 wk (usual dose); no standardized regimen established; early open-label phase I/II study showed varying doses, from 1 infusion of 100 mg/m2 to 4 weekly infusions of 375 mg/m2, without cyclophosphamide bolus or glucocorticoid treatment, significantly reduced Systemic Lupus Activity Measure score over 1 y in 65% of patients
Pediatric
Not established
Coadministration with cisplatin known to cause severe renal toxicity, including acute renal failure; may interfere with immune response to live-virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine); abciximab, antihypertensives, echinacea
Documented hypersensitivity; IgE-mediated reaction to murine proteins
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor CBC and platelet counts regularly during and few months posttreatment for occurrence of cytopenia; monitor human antichimeric antibody development (approximately 1% patients); monitor and treat associated infections (30% probability)
Severe infusion reactions have occurred, typically during the first infusion, with time to onset of 30-120 min; signs and symptoms may include urticaria, hypotension, angioedema, hypoxia, or bronchospasm and may require interruption of infusion; most severe manifestations and sequelae include pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, and anaphylactic and anaphylactoid events; factors most commonly associated with fatal outcomes are female sex, pulmonary infiltrates, and chronic lymphocytic leukemia or mantle cell lymphoma; interrupt infusions for severe infusion reactions, and medication and supportive care measures provided; in most cases, infusion can be resumed at 50% reduction in rate when symptoms have completely resolved
With regard to tumor lysis syndrome (TLS), rapid reduction in tumor volume followed by acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia reported within 12-24 hr after first infusion; risk greater in patients with high numbers of circulating malignant cells (>25,000/µL) or high tumor burden; following complete resolution of the complications of TLS, rituximab has been tolerated when re-administered in conjunction with prophylactic therapy for TLS
Hepatitis B virus (HBV) reactivation with related fulminant hepatitis, hepatic failure, and death have been reported in some patients with hematologic malignancies; most patients received rituximab in combination with chemotherapy; median time to diagnosis of hepatitis approximately 4 mo after initiation of therapy and approximately 1 mo after last dose; discontinue rituximab and any concomitant chemotherapy in any patients who develop viral hepatitis and initiate appropriate treatment; data regarding safety of resuming rituximab in patients who develop hepatitis subsequent to HBV reactivation are insufficient
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| Differential Diagnoses & Workup: Lupus Erythematosus, Acute |
 Treatment & Medication: Lupus Erythematosus, Acute |
| Follow-up: Lupus Erythematosus, Acute |
| Multimedia: Lupus Erythematosus, Acute |
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References
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Further Reading
Keywords
acute lupus erythematosus, acute cutaneous lupus erythematosus, ACLE, LE, subacute cutaneous lupus erythematosus, SCLE, chronic cutaneous lupus erythematosus, CCLE, butterfly rash, malar rash, photosensitive lupus dermatitis
