AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Systemic lupus erythematosus (SLE) is an inflammatory connective tissue disease with variable manifestations. SLE may affect many organ systems with immune complexes and a large array of autoantibodies, particularly antinuclear antibodies (ANAs).

Pathophysiology

The damage that results with SLE is from the excessive deposition of immune complexes and the resultant organ-specific inflammatory response found in the blood vessels, kidneys, connective tissue, and skin.

Frequency

United States

The incidence of SLE in the United States is 50-100 cases per 100,000 population. A report indicates that 239,000 people in the United States have suspected or definite SLE.

International

Prevalence is about the same worldwide (50-100 cases per 100,000 population; the condition appears to be common in China, in Southeast Asia, and among blacks in the Caribbean.

Mortality/Morbidity

• The 10-year survival rate is 70-90% for individuals with SLE.
• Female patients with onset of the disease after age 60 years have the most favorable prognoses.
• Children with SLE have a less favorable prognosis.
• Renal failure and intercurrent infections are the most common causes of death associated with SLE.
• Prognosis in the last 50 years has improved from a 10-year survival rate of 10% to 90% in the last decade.
• Diffuse central nervous system (CNS) disease is another common cause of death.

Race

• The highest incidence of SLE is among Asians in Hawaii, blacks, and certain groups of Native Americans.
• African American women are 3 times more likely than Caucasian women to be affected by SLE.

Sex

• SLE occurs more frequently in women, with a female-to-male ratio of 8:1-13:1 in adults.SLE is 3 times more common in African-American women than white women in United States.
• Women are more prone to SLE in their childbearing years.
• During the first 10 years of life, girls develop SLE 3-7 times more often than boys.

Age

The onset of SLE occurs primarily in patients aged 16-55 years.

• It is uncommon after the age of 50.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Potential symptoms of systemic lupus erythematosus (SLE) include the following:

• Constitutional - Affect most patients at some point during the disease
• • Fatigue
  • A general feeling of unwellness
• Musculoskeletal - Most commonly affects patients early in SLE with 90% having arthralgias and 50% experiencing inflammatory arthritis
• • Arthralgia
  • Myalgia
  • Nonrestorative sleep
• Cardiovascular - Raynaud phenomenon
• Pulmonary - Pleuritic chest pain
• Genitourinary - Menstrual irregularities
• Neuropsychiatric
• • Headaches
  • Seizures
  • Anxiety disorders
  • Phobias
  • Manias
  • Depression
• Gastrointestinal
• • Diffuse abdominal pain
  • Nausea/vomiting
  • Dysphagia

Physical

Potential physical findings in SLE include the following:

• Constitutional
• • Weight loss
  • Weight gain (in patients treated with prednisone)
  • Fever
• Musculocutaneous
• • Hair loss
  • Discoid lupus
  • Acute cutaneous lupus
  • Butterfly rash
    • Malar
    • Erythematosus
    • Elevated
    • Pruritic
    • Painful
  • Livedo reticularis
  • Vesicular or bullous lesions
  • Acute or chronic urticaria
  • Telangiectasis
  • Periungual erythema
  • Palmar erythema or nodules
  • Purpura
  • Panniculitis
  • Ulcerations
  • Dry eyes
  • Dry mouth
• Musculoskeletal
• • Migratory, transient, and symmetric arthritis, most commonly in the hands and knees
  • Secondary fibromyalgia
• Cardiovascular
• • Raynaud phenomenon - Occurs in about half of patients; especially in hands and feet; skin color changes occur
  • Hypertension
• Pulmonary - Effusions
• Renal - Edema
• Neuropsychiatric
• • Chorea
  • Ataxia
  • Transverse myelitis
  • Asymmetric mononeuritis multiplex
  • Cranial nerve neuropathies
• Ophthalmologic
• • Cotton-wool exudates
  • Conjunctivitis or episcleritis

Causes

• The cause of SLE is unknown.
• SLE is an immunologic disorder with the production of autoantibodies.
• Sunlight can trigger the onset of SLE.
• Certain medicines may trigger SLE, as they initiate the immune response in susceptible individuals. The 2 most common medications are the following:
• • Hydralazine
  • Procainamide
• Others medications that may trigger SLE include the following:
• • Anticonvulsants
  • Antiemetics
  • Antituberculars
  • Antibiotics

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Undifferentiated connective tissue disease
Scleroderma CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) syndrome
Dermatomyositis or polymyositis
Mixed connective tissue disease
Sjögren syndrome
Antiphospholipid syndrome
Autoimmune thyroid disease
Drug-induced lupus

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Individual antinuclear antibody tests
• • Refer to the American Rheumatism Association Criteria Table, which provides more than laboratory criteria for individual antinuclear antibody (ANA) tests.
  • High titer of double-stranded DNA antibodies is the most specific test in active SLE.
  • Virtually all patients with systemic lupus erythematosus (SLE) have an ANA titer of 1:80 or higher.
  • The anti-Smith antigen is observed in 25% of patients with SLE overall, with 10-20% whites and 30-40% blacks and Asians.
  • Lupus erythematosus (LE) preparation is found in most patients with active SLE.
• False positive Venereal Disease Research Laboratory (VDRL) is part of the family of antiphospholipid antibodies.
• • Lupus anticoagulant
  • Anticardiolipin AB
  • Hypocomplementemia (not always specific but useful in following course)
  • Abnormal liver function tests
  • Erythrocyte sedimentation rate (ERS) - Used as a measure of inflammation in lupus and other diseases
  • CBC to evaluate anemia, leukopenia, and/or thrombocytopenia
  • Urinalysis usually abnormal with proteinuria and cellular casts in lupus nephritis
  • Serum creatinine, creatinine clearance, and 24-hour urine protein in patients suspected of lupus nephritis
  • Elevated serum creatinine level (may herald worsening of lupus nephritis)
  • Twenty-four hour protein to evaluate filtering function of the kidneys
• Electromyographic findings in patients who develop polymyositis or dermatomyositis
• • There is usually a patchy pattern to needle exam; if one site is negative, other sites need to be investigated.
  • Watch for fibrillation potentials or positive sharp waves.

Imaging Studies

• CT scan and MRI can be used to evaluate CNS involvement.

Other Tests

• Dual energy x-ray absorptiometry (DEXA)
• • An excellent test used to diagnose osteoporosis
  • Used in postmenopausal women and patients on long-term corticosteroids
  • Also used in individuals with other risk factors for osteoporosis

Procedures

• Skin biopsy for lupus band test (demonstrates immune complex and complement deposition but is not specific for lupus)

Histologic Findings

Necrotizing vasculitis involving small arteries and arterioles may be seen in any tissue. Arteritis shows fibrinoid deposits in vessel walls. The kidney has 5 patterns that may be seen.

• Mesangial lupus glomerulonephritis
• Focal proliferative glomerulonephritis
• Diffuse proliferative glomerulonephritis
• Membranous glomerulonephritis
• Normal (rare)

Skin involvement

• Liquefactive degeneration of the basal layer of the epidermis is noted, as well as edema at the dermal junction.
• Dermis shows variable edema and perivascular mononuclear infiltrates.
• Vasculitis with fibrinoid necrosis may be prominent.
• Deposition of immunoglobulin and complement along the dermoepidermal junction under immunofluorescence microscopy is seen. Changes of this nature may be seen in scleroderma or dermatomyositis.

Joint involvement

• A nonerosive synovitis with little deformity
• In the acute phase of arthritis in SLE, exudation of neutrophils and fibrin into the synovium and a perivascular mononuclear infiltrate in the subsynovial tissue occurs.

Central nervous system

• No significant vasculitis is present.
• Noninflammatory occlusion of small vessels by intimal proliferation sometimes is seen.

Serosal cavity involvement

• Pericarditis is the primary finding in the cardiovascular system.
• Myocarditis may be present, but it is less common.
• Coronary artery disease due to atherosclerosis is seen in young people particularly with long-standing SLE, especially if they have been treated with corticosteroids.

Spleen

• Capsular thickening is common in patients with SLE.
• Follicular hyperplasia also is a common finding.
• Plasma cells usually are seen in the pulp and contain immunoglobulins of the IgG and IgM variety.

Lungs

• Pleuritis and pleural effusions are the most common pulmonary findings and affect almost 50% of patients with SLE.
• Evidence of alveolar injury with edema and hemorrhage is less frequent.

Other organs and tissues

• Acute vasculitis may be seen in the portal tracts of the liver with lymphocytic infiltrates.
• LE cells may be noted in the bone marrow.
• Lymph nodes may be enlarged and have hyperactive follicles, as well as plasma cells.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Rehabilitation Program

Physical Therapy

Physical therapy (PT) is often beneficial for patients with systemic lupus erythematosus (SLE). The role of the physical therapist is to assess each patient and determine an effective plan of care to help reduce pain, stiffness, and inflammation, as well as to improve joint range of motion (ROM) and functional mobility. Key points to keep in mind when developing a PT program for a patient with SLE include the following:

• Exercises should be individualized. For those with predominant arthralgias or arthritis, techniques used in rheumatoid arthritis may be helpful.
• Aerobic exercise might improve aerobic capacity in patients with mild SLE.
• Incorporate isometric exercises for patients with joint inflammation, especially for the hip and the knee to help maintain biomechanical stability.
• Isotonic exercises can be used when there is reduced or absent joint inflammation.
• Transfers and ambulation activities are important for maintaining mobility.
• Strengthening exercises are initiated when appropriate. Fatigue may hinder progress in some patients.
• If pain lasts more than 1-1.5 hours following activity, the exercise regimen should be reduced in intensity and/or duration.
• ROM exercises in the presence of inflammation may induce more pain. Isometric exercises may be tolerated better. Hydrocollator packs can be helpful prior to completing ROM to help reduce pain and stiffness.
• Proper positioning may prevent joint contractures in patients with SLE. Do not use a pillow under a painful knee.
• Ultrasound (US) is a modality commonly used to provide deep heat to the affected joint, but it should not be used in the presence of inflammation. When US is used to improve ROM, the joint should be moved simultaneously with application of the US.
• Heat and US are indicated for chronic joint pain, while ice is the preferred modality for inflamed joints.
• A pool, when available, is an excellent setting for exercising inflamed joints, both because of the buoyancy of the water (providing unloading of the joint) and because the warm water is soothing.
• Pacing strategies and breathing exercises are useful when severe cardiac and pulmonary problems are apparent.
• Assistive devices such as canes and walkers are often helpful.

Occupational Therapy

The role of the occupational therapist (OT) is to help the patient restore their functional independence to the extent possible in spite of the problems caused by the disease. Principles of occupational therapy for patients with SLE include the following:

• Activities of daily living (ADL) are encouraged and may require training with special equipment, techniques, and procedures. ADL activities include feeding, dressing, bathing, toileting, grooming, and homemaking.
• Adaptive equipment may be necessary for patients to complete ADL tasks; some of the more common adaptive equipment includes a raised toilet seat, splints, and reachers. Elastic (no tie) shoelaces and wide-handled tools may increase the degree of independence.
• Educating the patient in joint conservation techniques to protect the joints from damage is important.
• Fatigue is one of the most frequent symptoms that needs to be dealt with in patients with SLE. The OT can be helpful in teaching the patient energy conservation techniques, frequently using adaptive equipment.
• A home safety evaluation may need to be completed, and the OT can provide recommendations for equipment (eg, bathtub bench, raised toilet seat, grab bar) to increase the patient's independence and safety with mobility at home.
• Paraffin baths are comforting for patients with hand involvement and may improve use.
• Gentleness is important.

Speech Therapy

The speech pathologist can be helpful when a patient has slurred speech, difficulty understanding speech, or the patient has difficulty speaking appropriately. These individuals with swallowing problems also can be evaluated and treated by the speech pathologist.

Recreational Therapy

The role of the recreational therapist is to involve the patient in enjoyable activities that have therapeutic value. A patient who has painful or weak hands, for example, may benefit from putting a jigsaw puzzle together. Doing a jigsaw puzzle is a light activity that enhances the patient's eye-hand coordination and ability to match pieces by color. Patients can do this while standing or sitting (whichever is most appropriate) and at the same time can be socializing with other patients.

Medical Issues/Complications

• Joints frequently are involved in SLE and often are the first feature to be noticed. The condition usually takes the form of arthritis. Typically, joints are affected symmetrically.
• • SLE does not destroy bone as rheumatoid arthritis does.

  • The arthritis most often is controlled easily with nonsteroidal anti-inflammatory agents (NSAIDs) or low-dose steroids. The physician may inject steroids locally into a joint.

  • Methotrexate is another agent that may be used in severe arthritis.

• Muscular aching is common and may increase when the disease flares.
• • NSAIDs usually provide relief of discomfort.

  • Myositis is rare and causes weakness, typically most severe in the shoulders and thighs.
    • Elevated creatine kinase (CK) helps confirm the presence of muscular aching. CK also can be used to follow the progress of treatment.

    • Results of electromyography (EMG) show abnormalities in patients with SLE; polyphasic motor unit potentials are small.

    • Muscle biopsy shows changes of inflammation in the muscle sample.

    • A maintenance dose of steroids may be required to control the inflammation.

  • Muscle weakness may result from the use of steroids; steroid myopathy may develop. Steroid myopathy sometimes can be difficult to differentiate from the weakness of myositis.
    • Steroid myopathy is present typically in the proximal thigh and shoulder muscles.

    • CK levels are within the reference range in patients with SLE, unlike in cases of myositis.

    • Muscle weakness should improve when the steroid dose is reduced.

• Heart function and circulation can be affected in patients with SLE.
  • Pericarditis (common)
    • Chest pain occurs and can be intermittent. This pain is often mild, but it can be severe. The chest pain can be sharp and retrosternal.

    • Diagnosis of pericarditis is through the presence of a pericardial rub, electrocardiogram (ECG), and echocardiogram (ECHO).

    • Pericarditis is treated with NSAIDs and prednisone.
  • Myocarditis (less common)
    • Shortness of breath may be reported on exertion and while the patient is lying supine.

    • Orthopnea is noted and is aggravated when the patient is lying flat.

    • Cardiac arrhythmias may be present.

    • Peripheral edema also may be associated with myocarditis.

    • Diagnosis is with increased cardiac CK, ECG, and ECHO studies.

    • Treatment of myocarditis is with steroids.
  • Endocarditis (less common)
    • Heart murmurs often are associated with endocarditis.

    • Diagnosis of endocarditis is with ECHO.

    • Treatment of endocarditis should include prophylactic antibiotics.
  • Myocardial infarction (MI): Some studies show that MI is 9 times more common in patients with SLE than in healthy individuals.
  • Raynaud phenomenon
    • This condition usually involves the fingers, but it also can be observed in the toes.

    • Precipitating factors commonly include cold and stress.

    • Treatment of Raynaud phenomenon is to stay warm in the winter, discontinue smoking, and use calcium channel blockers.
  • Antiphospholipid syndrome results in abnormal clotting of the blood. Clinical manifestations of antiphospholipid syndrome may include the following:
    • Deep venous thrombosis

    • Miscarriages

    • Low platelets

    • Migraine headaches

    • Livedo reticularis

    • Treatment of antiphospholipid syndrome is with aspirin, unless there is prior history of miscarriage, and then use heparin.
• Lungs
  • Pleuritis is the most common pulmonary manifestation.
    • Diagnosis is through finding of a pleuritic rub.

    • Treatment is with NSAIDs or steroids.
  • Pneumonitis is uncommon, but, when it occurs, SLE usually is active elsewhere with evidence of a skin rash or arthritic flare.

• Gastrointestinal
  • Symptoms usually are related to the medications used for therapy.

  • Abdominal pain due to SLE-related vasculitis or peritonitis
    • This abdominal pain may be associated with nausea, vomiting, diarrhea, or bleeding.

    • SLE is treated with NSAIDs and steroids.

  • Medication-induced ulcers
    • These ulcers usually give midepigastric or right upper quadrant pain.

    • Food or antacids may relieve the pain.

    • Bleeding may occur.

    • Individuals aged 60 years and older are most at risk.

• Immune system
  • If the patient is on medication that suppresses the immune system, he/she is susceptible to tuberculosis or an infection with fungal organisms. Herpes zoster may be related to the same mechanism.

  • Any infection should be treated promptly.

  • All important vaccines, such as those for pneumonia and influenza, should be obtained.

• Renal system
  • Renal complications are present in about 50% of patients with SLE.

  • The pathology that can occur ranges from asymptomatic mesangial proliferation to renal failure.
    • Proteinuria

    • Microscopic hematuria

    • Pyuria

    • Azotemia

    • Granular and cell casts

Surgical Intervention

• Biopsy frequently is helpful to the physician when making the diagnosis.
• Renal transplantation is most advisable when SLE is inactive.
• Dialysis may be indicated for patients with SLE.
• Cataract surgery may be necessary for those patients taking corticosteroid medications due to increased incidence of cataracts.
• Fractures
  • Patients on corticosteroids are prone to osteoporosis and fractures with relatively minor stress or injury.
  • Hip, wrist, and spine are the most common sites of fracture following a fall.
• Avascular necrosis
  • The femoral head is the most common site for occurrence of avascular necrosis.
  • Decompression, bone grafting, osteotomy, and electrical stimulation are used to prevent progression of the condition.
  • Endoprosthesis and a total hip replacement are therapeutic treatments.

Consultations

• Clinical psychologist
• • Every chronic illness results in psychological problems, and, in the case of SLE, mental difficulties may develop that the psychologist can help to sort out.
  • Some of the medications used can cause mental problems and the clinical psychologist can help the patient to deal with such disorders.
  • When indicated, the clinical psychologist can provide psychotherapy.
  • Supportive therapy is also the province of the psychologist. The psychologist frequently directs support groups as well.
• Other consultations, based on organ systems affected
• • Dermatologist
  • Nephrologist
  • Neurologist
  • Psychologist and/or neuropsychologist
  • Ophthalmologist
  • Hematologist
  • Orthopedist
  • Rheumatologist
  • Physiatrist
  • Dentist

Other Treatment

• Plasmapheresis usually is reserved for those with rapidly progressing disease.
• Refer to the Medication section below.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to induce remission, reduce morbidity, and prevent complications.

Drug Category: Nonsteroidal anti-inflammatory drugs

Ibuprofen and naproxen are 2 of many examples of NSAIDs that are being added rapidly to the list of available options. Other drugs that can be used, but are not described further, include diclofenac, ketoprofen, ketorolac, nabumetone, oxaprozin, piroxicam, sulindac, and tolmetin. NSAIDs are used to reduce inflammation and pain, control fever, arthritis, pericarditis, and pleuritis. These drugs inhibit cyclo-oxygenase (COX), which is the enzyme that catalyzes the synthesis of cyclic endoperoxides from arachidonic acid to form prostaglandins.

Two COX isoenzymes, COX-1 and COX-2, exist. Inhibition of COX-1 is considered a major contributor to NSAID GI toxicity. Some NSAID drugs inhibit both COX-1 and COX-2, while most NSAIDs are mainly COX-1 selective. If one NSAID does not work, another may. Several COX-2 selective agents are now available. When used at therapeutic doses, these selectively inhibit the COX-2 isoenzyme (the COX-1 isoenzyme is not inhibited) and GI toxicity may be decreased. Several COX-2 inhibitors were withdrawn from the market because of possible cardiac complications. Rofecoxib (Vioxx) was withdrawn in September, 2004 and valdecoxib (Bextra) was withdrawn in April, 2005. Celecoxib (Celebrex) is still available as a COX-2 inhibitor.

Drug Category: Cyclooxygenase-2 inhibitors

Indications for specific types of pain vary for each drug, but they may include pain associated with osteoarthritis, rheumatoid arthritis, menstrual pain, or general pain. Although increased cost can be a negative factor, the incidence of costly and potentially fatal GI bleeds is clearly less with COX-2 inhibitors than with traditional NSAIDs. Ongoing analysis of cost avoidance of GI bleeds will further define the populations that will find COX-2 inhibitors the most beneficial.

Drug Category: Corticosteroids

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Drug Category: Immunosuppressive agents

Used in patients with the most severe disease; immunosuppressive agents reduce humoral and cellular responses; azathioprine and cyclophosphamide are the most commonly used drugs.

Drug Category: Antimalarials

Some agents in this category have immunosuppressive properties.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Follow-up medical care of patients with systemic lupus erythematosus (SLE) has to be ongoing. One physician should coordinate the patient's care. Both the physician and the patient must be alert to subtle changes in symptoms that may indicate a flare-up in the disease process.
• • Assessing the disease activity is crucial; treatment decisions are based on the assessment.
  • Measuring disease activity has been attempted many times. In the last 20 years several have been validated.
    • BILAG: The British Isles Lupus Assessment Group
    • SLAM: Systemic Lupus Activity Measure
    • ECLAM: European Community Lupus Activity Measure
    • SLEDAI: Systemic Lupus Erythematosus Disease Activity Index
    • The BILAG is a more comprehensive, at a glance overview in 8 organs/systems while the others are global indices.
  • At each clinic visit, a CBC, sedimentation rate, and C-reactive protein are recommended to differentiate a flare from infection.
  • A urea and serum creatinine level should be checked. A renal problem is considered with a rapidly rising urea and/or creatinine level.

Further Outpatient Care

• Refer to the Rehabilitation Program section for a discussion of outpatient treatment for patients with SLE.
• Liver function tests are needed when a patient is receiving particular disease-modifying antirheumatic drugs.
• Urine should be checked for red or white cells, and protein and cellular casts. Findings may indicate silent renal disease.

Complications

• For discussion of potential complications that are associated with SLE, see the Medical Issues/Complications section.

Patient Education

• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center, Arthritis Center, and Muscle Disorders Center. Also, see eMedicine's patient education articles, Lupus (Systemic Lupus Erythematosus), Chronic Fatigue Syndrome, and Chronic Pain.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• The American College of Rheumatology Classification system for SLE suggests that a person may be classified as having lupus if he or she has 4 or more of the following 11 criteria:
  • Malar rash
  • Discoid lupus
  • Photosensitivity
  • Oral or nasal ulcers
  • Arthritis
  • Serositis
  • Renal with blood or protein in urine
  • Seizures or mental illness
  • Hematologic disorders
  • Immunologic disorders
    • Positive LE test
    • Anti-DNA antibody
    • Anti-Smith antibody
    • False positive test for syphilis
  • A positive antinuclear antibody

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• American College of Rheumatology. The American College of Rheumatology response criteria for systemic lupus erythematosus clinical trials: measures of overall disease activity. Arthritis Rheum. Nov 2004;50(11):3418-26.
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• Chambers SA, Isenberg D. Anti-B cell therapy (rituximab) in the treatment of autoimmune diseases. Lupus. 2005;14(3):210-4.
• Clarke-Jenssen AC, Fredriksen PM, Lilleby V, Mengshoel AM. Effects of supervised aerobic exercise in patients with systemic lupus erythematosus: a pilot study. Arthritis Rheum. Apr 15 2005;53(2):308-12.
• Cozen L, Wallace DJ. Avascular necrosis in systemic lupus erythematosus: clinical associations and a 47-year perspective. Am J Orthop. May 1998;27(5):352-4. [Medline].
• Esdaile JM, Abrahamowicz M, Joseph L, et al. Laboratory tests as predictors of disease exacerbations in systemic lupus erythematosus. Why some tests fail. Arthritis Rheum. Mar 1996;39(3):370-8. [Medline].
• Fernando MM, Isenberg DA. How to monitor SLE in routine clinical practice. Ann Rheum Dis. Apr 2005;64(4):524-7.
• Foote RA, Kimbrough SM, Stevens JC. Lupus myositis. Muscle Nerve. Jan 1982;5(1):65-8.
• Frontera WR, Slovik DM, Dawson DM. Exercise in Rehabilitation Medicine. 2nd ed:. 2006;175-176.
• Gaffney PM, Moser KL, Graham RR, Behrens TW. Recent advances in the genetics of systemic lupus erythematosus. Rheum Dis Clin North Am. Feb 2002;28(1):111-26. [Medline].
• Goldblatt F, Isenberg DA. New therapies for systemic lupus erythematosus. Clin Exp Immunol. May 2005;140(2):205-12.
• Goodman D, Morrissey S, Graham D, Bossingham D. Illness representations of systemic lupus erythematosus. Qual Health Res. May 2005;15(5):606-19.
• Hicks JE, Miller F, Plotz P, et al. Isometric exercise increases strength and does not produce sustained creatinine phosphokinase increases in a patient with polymyositis. J Rheumatol. Aug 1993;20(8):1399-401. [Medline].
• Lahita R, ed. Systemic Lupus Erythematosus. 4th ed. San Diego, Calif: Academic Press; 2004.
• Lehman JF, Brunner GD, Martinis AJ, McMillan JA. Ultrasonic effects as demonstrated in live pigs with surgical metallic implants. Arch Phys Med. 1959;40:483.
• Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med. Mar 7 2002;346(10):752-63. [Medline].
• Omdal R, Brokstad K, Waterloo K, et al. Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors. Eur J Neurol. May 2005;12(5):392-8.
• Petri M, Barr SG, Zonana-Nach A, Magder L. Measures of disease activity, damage, and health status: the Hopkins Lupus Cohort experience. J Rheumatol. Feb 1999;26(2):502-3. [Medline].
• Traynor AE, Schroeder J, Rosa RM, et al. Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study. Lancet. Aug 26 2000;356(9231):701-7. [Medline].
• Wallace DJ, Hahn BH, eds. Dubois' Lupus Erythematosus. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2002.
• Weber DC, Stillwell GK. In: Sinaki M, ed. Basic Clinical Rehabilitation Medicine. 2nd ed. St Louis, Mo: Mosby; 1993.

Article Last Updated: Feb 9, 2007