eMedicine Specialties > Emergency Medicine > Rheumatology

Systemic Lupus Erythematosus

Mark J Leber, MD, MPH, FACEP, Attending Physician and Faculty, Department of Emergency Medicine and Residency Program, Lincoln Medical and Mental Health Center
Viraj S Lakdawala, MD, Resident Physician, Department of Emergency Medicine, Lincoln Medical and Mental Health Center, Bronx, NY

Updated: Oct 27, 2009

Introduction

Background

Systemic lupus erythematosus (SLE) is a multiorgan system autoimmune disease with numerous immunological and clinical manifestations. It is characterized by an autoantibody response to nuclear and cytoplasmic antigens. The disease mainly involves the skin, joints, kidneys, blood cells, and nervous system. Diagnosing and managing SLE in the emergency department can be very challenging if it is not considered in one's differential diagnosis. Also, the laboratory testing of SLE may be unavailable on an emergent basis.

Pathophysiology

Systemic lupus erythematosus (SLE) is a multifactorial disease involving genetic, environmental, and hormonal factors. Its precise pathogenesis is unclear. There is growing evidence in favor of a clearance deficiency of apoptotic cells as the core mechanism in the pathogenesis of SLE.¹ Defective clearance of apoptotic cells causes secondary necrosis with release of intracellular content and inflammatory mediators. Macrophages respond and present self-antigens to T and B cells.¹

Pathogenic autoantibodies are the primary cause of tissue damage in patients with lupus. The production of these antibodies arises by means of complex mechanisms involving every key facet of the immune system.² The abnormal cellular and humoral response to the formation of these autoantibodies is modulated by genetic, environmental, and hormonal factors:

• Genetic factors
  • Genes of the MHC HLA-A1, B8, and DR3 have been linked to lupus.
  • Genetic deficiency of complement factors C1q, C2, or C4
• Environmental factors³
  • Occupational exposure - Silica, pesticides, mercury
  • Drugs - Many drugs have been implicated in drug-induced lupus.
  • Sunlight
• Epstein-Barr virus (EBV) has also been identified as a possible factor in the development of lupus.³

Frequency

United States

In the United States, the annual incidence of systemic lupus erythematosus (SLE) averages 5.1 per 100,000 per year. The incidence of SLE in black women is approximately 4 times higher than in white women. SLE is more frequent in Asian women than in white women.⁴

The reported prevalence of SLE in the population is 52 cases per 100,000.⁵

The frequency of SLE could be increasing due to mild forms of the disease that are being recognized.

International

The highest prevalences of systemic lupus erythematosus (SLE) were reported in Italy, Spain, Martinique, and the UK Afro-Caribbean population.⁵ SLE is more common in women with West African ancestry who have emigrated from their home area, suggesting that there may be an environmental trigger as well as a genetic basis for their disease.

Mortality/Morbidity

The life expectancy of such patients has improved from an approximate 4-year survival rate of 50% in the 1950s to a 15-year survival rate of 80% today.⁶ A patient in whom SLE is diagnosed by age 20 years still has a 1 in 6 chance of dying within 15 years, most often from lupus or infection.⁷ After 35, the patient is more likely to die from myocardial infarction or stroke.⁷

Infectious diseases have emerged as one of the leading causes of morbidity and mortality, accounting for 29% of all deaths in these patients.⁸

Women with SLE between 35 and 44 years of age had a 52-fold higher risk of having a myocardial infarction than matched women from the Framingham cohort.⁹

Ten-year survival rates in other countries in Asia and Africa are significantly lower, ranging from 60-70%.^10,11,12

Race

Black women have a higher rate of SLE than any other race, followed by Asians, then white women.⁵

In the United States, black women are 4 times more likely to have SLE than white women.⁵

Sex

For all ages, the female-to-male ratio is 7:1 and 11:1 during the childbearing years.¹³

Age

Onset of systemic lupus erythematosus (SLE) is usually after puberty, typically in the 20s and 30s.

Twenty percent of all cases of lupus are diagnosed during the first 2 decades of life.¹⁴

Clinical

History

The triad of fever, joint pain, and rash in a woman of childbearing age should suggest the diagnosis of systemic lupus erythematosus (SLE). These 3 symptoms are some of the most commonly found symptoms in patients presenting with SLE.^15,16

The American College of Rheumatology last updated the diagnostic criteria for SLE in 1997. The most current criteria are listed below.^17,18
 

Physical

• Fever is a challenging problem in systemic lupus erythematosus (SLE). It can be a manifestation of active lupus or a representation of infection, malignancy, or drug reaction. Lower-grade temperature is observed in patients on immunosuppressive agents.
  • Patients with fever need to have infectious causes ruled out — both viral and bacterial. Patients with SLE who are on immunosuppressive therapy are at a higher risk of death due to viruses (ie, herpes simplex virus [HSV], cytomegalovirus [CMV], varicella-zoster virus [VZV]) and should be treated accordingly if a viral illness is suspected.¹⁹
  • An infection can mimic a lupus flare and delays in diagnosis and institution of
    treatment result in increased mortality.²⁰
• Malar rash is a fixed erythema that spares the nasolabial folds. It is a butterfly rash that can be flat or raised over the cheeks and bridge of the nose. It also often involves the chin and ears.

The classic malar rash, also known as a butterfly rash, with distribution over the cheeks and nasal bridge. Note that the fixed erythema, sometimes with mild induration as seen here, characteristically spares the nasolabial folds.

• Discoid rash occurs in 20% of patients with SLE and can result in disfiguring scars. The discoid rash can present as erythematous patches with keratotic scaling over sun-exposed areas of the skin. Systemic manifestations of SLE may be absent.
• Alopecia or loss of hair may occur.
• Lupus should be considered in all patients who experience painless or painful oral or vaginal ulcers.
• Gastrointestinal findings include vague abdominal discomfort, nausea, and diarrhea. Acute crampy abdominal pain, vomiting, and diarrhea may signify vasculitis of the intestine.
• Joint findings
  • Tenderness, edema, and effusions accompany a polyarthritis that is symmetric, nonerosive, and usually nondeforming. The arthritis frequently involves the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the hands as well as the wrists and knees.
  • Consider avascular necrosis, which is common in patients who are taking glucocorticoids.
  • In addition, consider septic arthritis when one joint is inflamed out of proportion to all other joints.
• Central nervous system findings
  • All types of seizures have been reported; the most frequent is the grand mal seizure. Sensory or sensorimotor neuropathies are also common.
  • Incidence of stroke is high in the first 5 years of disease. Patients with antiphospholipid antibodies are at higher risk for such events.
• Funduscopic examination is important in patients with visual complaints. Retinal vasculitis can lead to blindness and is demonstrated by sheathed narrow retinal arterioles with white exudates adjacent to the vessels.
• The renal system can be affected leading to renal failure. Specific signs and symptoms of renal disease may not be apparent until advanced nephrotic syndrome or renal failure is present; therefore, obtaining a urine analysis and serum BUN and creatinine levels on a regular basis is important.
• Cardiovascular system findings
  • Atherosclerosis occurs prematurely in patients with SLE and is an independent risk factor for cardiovascular disease.
  • Pulmonary hypertension, vasculitis with digital infarcts, and splinter hemorrhages may be observed.
  • Systolic murmurs are reported in up to 70% of cases. They may be secondary to fever, hypoxia, anemia, or Libman-Sacks endocarditis (associated with antiphospholipid antibodies).
  • Pericarditis has an incidence of 20-30% and is the most common presentation of heart involvement. It is usually associated with small effusions, but it may involve larger effusions when uremia is concomitant. Myocarditis can cause heart failure, arrhythmias, and sudden death.
• Pulmonary findings
  • Tachypnea, cough, and fever are common manifestations of lupus pneumonitis.
  • Hemoptysis may signify pulmonary hemorrhage secondary to the disease. However, infection is the most common cause of infiltrates seen on radiographs.

Causes

• Many of the clinical manifestations of systemic lupus erythematosus (SLE) are caused by the effects of circulating immune complexes on various tissues or to the direct effects of antibodies to cell surface components.
• Whether polyclonal B-cell activation or a response to specific antigens exists is unclear.
• Cytotoxic T cells and suppressor T cells (which would normally downregulate immune responses) are decreased.
• The generation of polyclonal T-cell cytolytic activity is impaired.
• Helper (CD4⁺) T cells are increased.
• A lack of immune tolerance is observed in animal models.
• A high concordance rate (14-57%) of SLE is noted in monozygotic twins. Each patient manifests his or her disease differently.
• Five to twelve percent of relatives of patients with SLE have the disease.
• If a mother has SLE, her daughter's risk of developing the disease is 1:40, and her son's risk is 1:250.
• Administration of estrogen to postmenopausal women appears to double the risk of developing SLE.
• Breastfeeding is associated with a decreased risk of developing SLE.
• Viruses, for example, may stimulate specific cells in the immune network. Patients with SLE also have higher titers of antibodies to Epstein-Barr virus (EBV), have increased circulating EBV viral loads, and make antibodies to retroviruses, including to protein regions homologous to nuclear antigens.
• Trypanosomiasis or mycobacterial infections may induce anti-DNA antibodies or even lupuslike symptoms, and lupus flares may follow bacterial infections.
• Silica dust and cigarette smoking may increase the risk of developing SLE.
• Photosensitivity is clearly a precipitant of skin disease.
• The presence of antiphospholipid antibodies causes physical signs of thrombosis.

Differential Diagnoses

Other Problems to Be Considered

Drug-induced lupus: Before making a diagnosis of systemic lupus erythematosus (SLE), ruling out drugs as the cause of the condition is important. Table 1 shows the many pharmacologic agents associated with a lupuslike syndrome. Procainamide, hydralazine, and isoniazid have been studied the best. Many patients who take these medications have positive antinuclear antibody test results and other serologic findings. Only a few have the clinical manifestations. Drug-induced lupus differs from SLE by the following features:

• Sex ratios are nearly equal.
• Antibodies to histones are usually found in 80-90%.
• Nephritis and central nervous system features are not commonly present.
• No antibodies to native DNA or hypocomplementemia are present.
• When the drug is discontinued, the patient has resolution of clinical manifestations and reverting of abnormal laboratory values to normal.
• Newer syndrome of drug-induced SLE has been observed with minocycline and propylthiouracil. Both drugs have a decreased frequency of antihistone antibodies and anti–double-stranded DNA antibodies, and results for antineutrophil cytoplasmic antibodies are rarely positive.

Drugs Associated With Lupus Erythematosus

Workup

Laboratory Studies

• Simple laboratory tests may be helpful in making the diagnosis or in evaluating a flare. However, the diagnosis mostly depends on the historical and physical findings.
• Rarely, autoantibody tests should be obtained in the ED, unless the workup needs to be expedited because of a diagnosis that warrants immediate diagnosis (ie, pleural effusion, renal insufficiency, myocarditis, pericarditis).
• ECG may be warranted if the patient is experiencing chest pain, shortness of breath, or bradycardia.
• Complete blood cell count (CBC)
  • Leukopenia, which generally is a good index for disease activity
  • Lymphopenia
  • Anemia of chronic disease (60-80%)
  • Evidence of a hemolytic anemia (10%)
  • Cytotoxic therapy (can cause anemia or leukopenia)
  • Thrombocytopenia (30-50% of cases), which may be profound secondary to antiplatelet antibodies or to antiphospholipid antibodies
• The partial thromboplastin time (PTT) may be elevated secondary to lupus anticoagulant (antiphospholipid antibody), which is associated with thrombosis.
• Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or both
• Urinalysis
  • Pyuria
  • Hematuria
  • Granular casts
  • Proteinuria
• Chemistry, blood urea nitrogen (BUN), and creatinine levels
  • Usually not elevated at onset of disease
  • Can be useful for determining progression of renal disease
• Joint aspiration - Can be done when patient has a monoarticular/polyarticular arthritis
• Urine pregnancy test

Imaging Studies

• Chest radiographs may show the following:
  • Effusion
  • Infiltrates
  • Cardiomegaly
• Echocardiography is indicated for chest pain to rule out a pericardial effusion and any valvular pathology and to confirm any signs of pulmonary hypertension.
• Magnetic resonance imaging (MRI) is most useful for focal neurologic deficits or cognitive dysfunction.

This axial, T2-weighted brain MRI demonstrates an area of ischemia in the right periventricular white matter of a 41-year-old woman with long-standing systemic lupus erythematosus (SLE). She presented with headache and subtle cognitive impairments but no motor deficits. Faintly increased signal intensity was also seen on T1-weighted images, with a trace of enhancement following gadolinium that is too subtle to show on reproduced images. Distribution of the abnormality is consistent with occlusion of deep penetrating branches, such as may result from local vasculopathy, with no clinical or laboratory evidence of lupus anticoagulant or anticardiolipin antibody. Cardiac embolus from covert Libman-Sacks endocarditis remains less likely due to distribution.

• Computed tomography (CT) is useful for abdominal pain and suspected pancreatitis.
• Contrast angiography should be performed in determining the diagnosis of vasculitis. Lupus vasculitis affects medium-sized arteries and causes mesenteric or limb-threatening ischemia.

Other Tests

• Cerebrospinal fluid (CSF) analysis is recommended when the diagnosis of CSF lupus is in question or when infection is a possible cause of symptoms.
  • High protein levels occur in 50% of patients, and pleocytosis may be found.
  • Cerebritis is associated with high protein levels.
• Approximately 80% of patients with active CNS lupus will have an abnormal routine EEG.
  • Diffuse slow-wave activity is the pattern most typically associated with lupus, whereas focal changes are seen in patients with seizure disorder.
• Obtain serologies in the ED only with a definitive rheumatologic consultation and follow-up.
  • Antinuclear antibody (ANA), an antibody to nucleosomal DNA-histone complexes, is more than 95% sensitive but not very specific.
  • Double-stranded DNA and aa anti-Sm (anti-Smith) antibody tests are 100% specific for lupus. Elevated anti-ds-DNA may correlate with the degree of activity of lupus and with the level of nephritis.
• Antiphospholipid antibody
  • Antiphospholipid antibodies are only present in 30% of patients with SLE.
  • Antiphospholipid antibodies are associated with recurrent thrombosis and spontaneous abortions.
  • They are associated with normal-to-prolonged PT and prolonged plasma clot time.
  • A false-positive test result for syphilis may provide indirect evidence for the antiphospholipid antibody.
• Complement levels (total hemolytic complement [CH50], C3, and C4)
• Electrocardiographic changes in the assessment of chest pain may be due to pericarditis or premature coronary artery disease.

Procedures

Arthrocentesis - Cell count, viscosity, gross appearance

• Effusion can be inflammatory or noninflammatory.
• Cell count will reveal less than 25% PMN for noninflammatory or more than 50% for inflammatory.
• Viscosity will be low in inflammatory or high in noninflammatory.
• Gross appearance will be cloudy/yellow in inflammatory or straw-colored/clear in noninflammatory.

Treatment

Emergency Department Care

• Emergent complications of systemic lupus erythematosus (SLE) are managed in the usual manner.
  • These can include strokes, acute myocardial infarctions, hemoptysis, respiratory distress, and pulmonary emboli.
  • In patients who present with fever, treating for an infection empirically may be necessary until culture results have been received.
  • Individual treatment plans are beyond the scope of this article and are discussed in other articles (see Differentials and Complications).

Consultations

• Consultation with a rheumatologist indicated for patients who present with symptoms suggestive of SLE and for patients with known disease.
• For complications such as pericardial tamponade, pulmonary hemorrhage, renal failure, or cerebritis, the appropriate subspecialist needs to be consulted.
• For cases of pregnancy associated with antiphospholipid antibody, the patient should be followed up by a high-risk obstetrician due to the increased risk of preeclampsia and placental insufficiency.²²

Medication

Conservative management with nonsteroidal anti-inflammatory drugs, including salicylates, is recommended for arthritis, arthralgia, and myalgia not requiring immunosuppression. Only initiate high-dose glucocorticoids and cytotoxic agents by or in consultation with a rheumatologist. Patients with thrombosis require anticoagulation with warfarin for a target international normalized ratio (INR) of 3-3.5. Antibiotics may be appropriate in the treatment of ordinary and opportunistic infections.

Nonacetylated salicylates

These agents are indicated to manage the inflammatory process.

Choline magnesium trisalicylate (Trilisate)

An excellent initial management drug, which has less GI symptoms and less impairment of platelets and renal function than acetylated agents.
Salicylates have analgesic, antipyretic, anti-inflammatory, and antirheumatic effects. The pharmacologic effects of these agents are qualitatively similar. Their anti-inflammatory and analgesic activity may be mediated through the inhibition of the prostaglandin synthetase enzyme complex.

Dosing

Adult

500 mg to 1.5 g PO bid/tid
Maintenance dose: 1-4.5 g/d PO

Pediatric

<37 kg: 50 mg/kg/d PO divided bid
>37 kg: Administer as in adults

Interactions

Salicylate intoxication may occur with coadministration of carbonic anhydrase inhibitors; corticosteroids decrease salicylate serum levels; may have additive hypoprothrombinemic effect and may increase bleeding time

Contraindications

Documented hypersensitivity; bleeding disorders

Precautions

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

Associated with Reye syndrome in children and teenagers with influenza or chickenpox; discontinue if dizziness, ringing in ears, or impaired hearing occurs (may represent toxicity); caution in liver damage, preexisting hypoprothrombinemia, and vitamin K deficiency

Nonsteroidal anti-inflammatory drugs (NSAIDs)

These agents are most commonly used for the relief of mild-to-moderate pain. Although the effects of NSAIDs in the treatment of pain tend to be patient specific, ibuprofen is usually the DOC for initial therapy. Other options include fenoprofen, flurbiprofen, mefenamic acid, ketoprofen, indomethacin, and piroxicam.

Ibuprofen (Motrin, Nuprin, Ibuprin, Advil)

Usually DOC for treatment of mild-to-moderate pain, if no contraindications exist.
Inhibits inflammatory reactions and pain probably by decreasing activity of the enzyme cyclooxygenase, which results in inhibition of prostaglandin synthesis.

Dosing

Adult

400 mg PO q4-6h, 600 mg PO q6h, or 800 mg PO q8h; while symptoms persist; not to exceed 3.2 g/d

Pediatric

<6 months: Not established
6 months to 12 years: 10-70 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate upward to a maximum of 2.4 g/d
>12 years: Administer as in adults

Interactions

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; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Contraindications

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding

Precautions

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

Antimalarials

These agents are an alternative conservative therapy with both sunblocking and anti-inflammatory effects. Initiation of antimalarial therapy usually does not take place in the ED setting.

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. Used for treatment of discoid and systemic lupus erythematosus and rheumatoid arthritis.

Dosing

Adult

200-400 mg PO qd for several wk depending on response; 200 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

Interactions

Serum levels increase with cimetidine; magnesium trisilicate may decrease absorption

Contraindications

Documented hypersensitivity; psoriasis; retinal and visual field changes attributable to 4-aminoquinolones

Precautions

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 in children; perform periodic (6 mo) ophthalmologic examinations; test periodically for muscle weakness

Glucocorticoids

These agents have both anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli. High-dose glucocorticoids are used for severe SLE complications, such as hematologic or CNS disease, serositis, vasculitis, or glomerulonephritis.

Prednisone (Deltasone, Orasone, Sterapred)

Used as an immunosuppressant in treatment of autoimmune disorders. By reversing increased capillary permeability and suppressing PMN activity, it may decrease inflammation.

Dosing

Adult

5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve

Pediatric

4-5 mg/m²/d PO; alternatively, 1-2 mg/kg PO qd; taper over 2 wk as symptoms resolve

Interactions

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

Contraindications

Documented hypersensitivity; fungal, tubercular skin, connective tissue, or viral infections; peptic ulcer disease; hepatic dysfunction; GI disease

Precautions

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 with glucocorticoid use

Methylprednisolone (Solu-Medrol, Depo-Medrol, Adlone)

Useful in treatment of inflammatory and autoimmune reactions. By reversing increased capillary permeability and suppressing PMN activity, it may decrease inflammation.

Dosing

Adult

Loading dose: 125-250 mg IV
Maintenance dose: 0.5-1 mg/kg/dose IV q6h for up to 5 d

Pediatric

Loading dose: 2 mg/kg IV
Maintenance dose: 0.5-1 mg/kg/dose IV q6h for up to 5 d

Interactions

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

Contraindications

Documented hypersensitivity; viral, fungal or tubercular skin infections

Precautions

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

Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Immunosuppressives/cytotoxic agents

These agents are used in active SLE cases resistant to corticosteroids. Patients should be monitored closely because of the adverse effects, and these agents should be administered by experienced specialist physicians. These drugs are more beneficial when used in conjunction with glucocorticoids. Treatment with glucocorticoids plus cyclophosphamide is more beneficial, although more toxic, than treatment with glucocorticoids plus azathioprine.

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. Pediatric dosing is controversial and not first line.

Dosing

Adult

10-20 mg/kg IV q3-4wk or 1.5-2.5 mg/kg PO qd

Pediatric

Not established

Interactions

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

Contraindications

Documented hypersensitivity; severely depressed bone marrow function

Precautions

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

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. Pediatric dosing is controversial and not first line.

Dosing

Adult

1.5-2.5 mg/kg PO qd

Pediatric

Not established

Interactions

Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine

Contraindications

Documented hypersensitivity; low levels of serum thiopurine methyltransferase (TPMT)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level before therapy and monitor liver, renal, and hematologic function; pancreatitis rarely associated

Follow-up

Further Inpatient Care

• Patients with systemic lupus erythematosus (SLE) may require admission for treatment of severe complications, such as lupus nephritis (for pulse steroids, cytotoxic agents) or other entities responsive to high-dose steroids.
• Admit patients with neuropsychiatric presentation or stroke syndromes.
• Admit patients to appropriate service (rheumatology if available) with subspecialty consultations as needed.

Further Outpatient Care

• Conservative management is indicated for the symptomatic relief of arthralgia, arthritis, or myalgia with nonacetylated salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs), or low-dose glucocorticoids.

Inpatient & Outpatient Medications

• Nonacetylated salicylates or NSAIDs may be indicated.

Deterrence/Prevention

• Patients with systemic lupus erythematosus (SLE) should be encouraged to take steps to prevent sunburn by limiting sun exposure, wearing protective clothing, and using sunscreen that protects against both UV-A and UV-B. Exposure to UV light causes SLE to flare in approximately 70% of patients. Sunscreen should have an SPF of at least 15 and should be applied frequently (every 2-3 h) and in the quantity recommended by the manufacturer.

Photosensitive systemic lupus erythematosus (SLE) rashes typically occur on the face or extremities, which are sun-exposed regions. Photo courtesy of Dr. Erik Stratman, Marshfield Clinic.

• Patients should have yearly vaccinations for influenza. Pneumococcus vaccine should be updated every 3-6 years.²⁰
  • Hepatitis B vaccines are recommended.
  • Patients on high-dose immunotherapy should NOT receive live vaccines. 
• Although organ involvement requires specific drug therapy, a number of general issues are applicable to every patient with SLE.
• Patients should avoid exposure to direct or reflected sunlight and other sources of UV light. Use sunscreens that block both UV-A and UV-B with sun protection factor (SPF) of 30.
• A conservative approach is to recommend a balanced diet consisting of carbohydrates, proteins, and fats. However, the diet should be modified based on disease activity and response to therapy. Patients with active inflammatory disease and fever may require an increase in caloric intake.
• Glucocorticoids enhance appetite, resulting in potentially significant weight gain. Hunger can be somewhat lessened by the ingestion of water, antacids, proton pump inhibitors, and/or histamine H2 blockers. A low calorie diet should be instituted if significant weight gain occurs.
• Most patients with SLE have low serum levels of 25-hydroxyvitamin D (calcidiol), probably due at least in part to avoidance of sun exposure. Patients with low vitamin D levels should be treated with supplemental vitamin D.
• Patients on long-term glucocorticoids and postmenopausal women should ingest 800 units of vitamin D plus 1500 mg of calcium per day and/or a bisphosphonate to minimize the degree of bone loss. 
• Cigarette smoking may increase the risk of developing SLE, and smokers in general have more active disease. Patients should be counseled not to smoke or to quit smoking and be provided with help to do so. 
• Inactivity produced by acute illness causes a rapid loss of muscle mass and stamina resulting in a sense of fatigue. This can usually be treated with graded exercise. In selected refractory cases, relief can be obtained with antimalarial drugs.

Complications

• Vasculitis and its various complications (eg, intestinal perforations)
• Pericarditis
• Myocarditis
• Lupus pneumonitis
• Pulmonary hemorrhage, pulmonary hypertension
• Proliferative glomerulonephritis
• Hemolytic anemia, thrombocytopenia
• Intravascular thrombosis (eg, stroke and myocardial infarction)
• Complications of high-dose glucocorticoid therapy
• Complications of cytotoxic agents
• Recurrent spontaneous abortions

Prognosis

• Mortality of those with systemic lupus erythematosus (SLE) has decreased over the past 20 years.²³
• Five-year survival rate in Western countries ranges between 93-95%.²³
• Mortality typically in the first few years of illness is active disease (eg, CNS, renal, or cardiovascular disease) or infection due to immunosuppression, whereas late deaths are due to atherosclerosis.^23,9

Patient Education

• Patients should protect their skin from the sun.
• Compliance with medications and follow-up appointments is important.
• For excellent patient education resources, visit eMedicine's Immune System Center. Also, see eMedicine's patient education article Lupus (Systemic Lupus Erythematosus).
• For more information, see Medscape’s Lupus Resource Center.

Miscellaneous

Medicolegal Pitfalls

• Failure to evaluate for ordinary or opportunistic infections
• Failure to involve a rheumatologist or a primary care provider in the management and disposition of a patient

Special Concerns

• Whether flares of systemic lupus erythematosus (SLE) are more frequent during pregnancy is controversial. The flares do not seem to be exceedingly more serious compared with those in nonpregnant patients. Pregnancy outcomes are generally more likely to be complicated.
  • Increased rates of hypertension during pregnancy, premature delivery, unplanned cesarean delivery, postpartum hemorrhage, and maternal venous thromboembolism are all more frequent in women with SLE than in others.
  • Fetal growth restriction and neonatal deaths are also frequently seen in association with SLE.
  • Predictors for fetal loss include active nephritis at conception and the presence of antiphospholipid (aPL) antibodies.
• High-dose aspirin and NSAIDs should be avoided in the last few weeks of pregnancy.
• Hydroxychloroquine has not been shown to induce congenital malformations. Furthermore, unnecessary discontinuation of hydroxychloroquine during pregnancy may result in lupus flares.
• If indicated, prednisone, prednisolone, and methylprednisolone are the corticosteroids of choice during pregnancy because of their minimal placental transfer.

Multimedia

Media file 1: The classic malar rash, also known as a butterfly rash, with distribution over the cheeks and nasal bridge. Note that the fixed erythema, sometimes with mild induration as seen here, characteristically spares the nasolabial folds.

Media file 2: Photosensitive systemic lupus erythematosus (SLE) rashes typically occur on the face or extremities, which are sun-exposed regions. Photo courtesy of Dr. Erik Stratman, Marshfield Clinic.

Media file 3: This axial, T2-weighted brain MRI demonstrates an area of ischemia in the right periventricular white matter of a 41-year-old woman with long-standing systemic lupus erythematosus (SLE). She presented with headache and subtle cognitive impairments but no motor deficits. Faintly increased signal intensity was also seen on T1-weighted images, with a trace of enhancement following gadolinium that is too subtle to show on reproduced images. Distribution of the abnormality is consistent with occlusion of deep penetrating branches, such as may result from local vasculopathy, with no clinical or laboratory evidence of lupus anticoagulant or anticardiolipin antibody. Cardiac embolus from covert Libman-Sacks endocarditis remains less likely due to distribution.

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Keywords

systemic lupus erythematosus, SLE symptoms, SLE causes, SLE, autoimmune disease, lupus nephritis, lupus pneumonitis, pulmonary hypertension, stroke, myocardial infarction, septic arthritis, avascular necrosis, seizures, sensory neuropathies, sensorimotor neuropathies, retinal vasculitis, nephrotic syndrome, renal failure, vasculitis with digital infarcts, Libman-Sacks endocarditis, pericarditis, myocarditis, heart failure, arrhythmias

Contributor Information and Disclosures

Author

Mark J Leber, MD, MPH, FACEP, Attending Physician and Faculty, Department of Emergency Medicine and Residency Program, Lincoln Medical and Mental Health Center
Mark J Leber, MD, MPH, FACEP is a member of the following medical societies: American College of Emergency Physicians and American College of Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Viraj S Lakdawala, MD, Resident Physician, Department of Emergency Medicine, Lincoln Medical and Mental Health Center, Bronx, NY
Viraj S Lakdawala, MD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians
Disclosure: Nothing to disclose.

Medical Editor

Richard S Krause, MD, Senior Faculty, Department of Emergency Medicine, State University of New York at Buffalo School of Medicine
Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

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Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Gino A Farina, MD, Program Director, Associate Professor of Clinical Emergency Medicine, Department of Emergency Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine
Gino A Farina, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
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Chief Editor

Rick Kulkarni, MD, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
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The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Anuritha Tirumani, MD, to the development and writing of this article.

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