Brain Imaging Studies
Evaluation of neurologic involvement in SLE is complex. MRI scans, usually with contrast, are indicated for any clinical suspicion of central nervous system disease, such as seizures, cognitive dysfunction, new severe headache, chorea, or stroke symptoms. CT scans are far less definitive, except in stroke. Cerebral angiography or magnetic resonance angiography (MRA) is rarely helpful.
CT and MRI scans of the brain frequently demonstrate atrophy and infarcts (the latter including hyperintense areas in the white matter). These lesions correlate poorly with neurologic disease other than stroke syndromes.13 Findings on fluorodeoxy-glucose positron emission tomography (PET), magnetic resonance spectrography (MRS), and single-photon emission computed tomography (SPECT) are frequently abnormal even in asymptomatic patients and correlate poorly with all but the most severe neuropsychiatric disease.52 Interpretation of abnormal findings in asymptomatic patients is uncertain.53,54
Vascular Evaluation
Vascular evaluation is indicated when there is clinical suspicion of medium-size vascular occlusion. Ultrasound, Doppler studies, angiography, and MRA can demonstrate thromboem-bolic disease from antiphospholipid antibody or atherosclerosis. The small vessel vasculitis that occurs in SLE is usually beyond the resolution of these technologies.
Table 8 Commonly Abnormal Tests on Body Fluids in SLE
|
Test |
Abnormality |
Interpretation |
|
CBC |
Normochromic anemia, leukopenia (WBC ~3,000, thrombocytopenia) |
Active SLE |
|
ESR and CRP |
Elevated |
Active SLE |
|
Urinalysis |
Proteinuria, hematuria, leukocyturia, cylindruria |
Active lupus nephritis |
|
Coombs and reticulocyte count |
Positive, high |
Hemolytic anemia |
|
APTT, dRVVT |
High |
If confirmed with mixing test, lupus anticoagulant |
|
Antinuclear antibody |
Strongly positive |
Positive in almost all patients during active disease; not specific for lupus |
|
Anti-dsDNA antibody |
Strongly positive |
Positive in two thirds to three quarters of patients during active disease; diagnostic of lupus |
|
Anti-Sm antibody |
Positive |
Positive in one quarter to one third of patients; diagnostic of lupus |
|
Anti-SS-A, anti-SS-B, and anti-RNP antibodies |
Positive |
Positive in one third of patients; nonspecific |
|
Anticardiolipin antibody |
Positive |
Antiphospholipid antibody syndrome |
|
Complement C3, C4, and CH50 |
Low |
Lupus nephritis likely; also hemolytic anemia and cryoglobulinemia |
|
Cryoglobulin |
Present |
Active SLE |
|
BUN and serum creatinine |
Elevated |
Severe lupus nephritis, drug toxicity |
|
Liver function tests |
Elevated |
Drug toxicity (rarely, active SLE) |
|
CSF protein and cells |
Elevated |
Present in a minority of patients with CNS SLE |
|
Synovial fluid |
WBC 5,000-10,000, normal glucose level |
Lupus arthritis |
|
Pleural fluid, pericardial fluid |
WBC 5,000-10,000, normal glucose level, low complement, LE cells present |
Lupus serositis |
APTT—activated partial thromboplastin time
BUN—blood urea nitrogen
CBC—complete blood count
CNS—central nervous system
CRP—C-reactive protein
CSF—cerebrospinal fluid
dRVVT—dilute Russell viper venom time
ESR—erythrocyte sedimentation rate
WBC—white blood cells
Renal Evaluation
All lupus patients should have urinalyses performed, preferably at each clinic visit, because renal disease may appear de novo at any time. All patients with any abnormality on urinaly-sis or with an abnormal blood urea nitrogen (BUN) or serum cre-atinine level should have monitoring of 24-hour urine protein and creatinine clearance no less often than every 6 months. It is important to consider the results of renal testing in context: a serum creatinine level of 1.2 mg/dl may be within the laboratory range of normal, but in a 110 lb young woman, a level that high is very likely abnormal. Falling creatinine clearance always demands evaluation, even when the patient is clinically well.
Kidney biopsy The primary indication to perform a kidney biopsy is to help the physician make a treatment decision. Although abnormal biopsy results may be found in asymptomatic patients with normal urinalyses, it is not clear whether treatment of such patients improves outcome. The well patient with normal urinalysis results and normal renal function generally does not need a kidney biopsy, even if the anti-DNA antibody level is high and the complement level is low. The very ill patient with multisystem disease, including abnormal urinalysis results and abnormal renal function, likely will be treated aggressively anyway and does not need a kidney biopsy. The patient with mild systemic disease, mild urinary abnormalities, or both generally should undergo biopsy, because the decision for conservative or aggressive treatment may depend on the result. Occasionally, a biopsy is done to document end-stage, untreatable disease and thereby permit withdrawal of therapy. However, renal ultra-sonography can usually provide the same information.
Cardiac Evaluation
Cardiac monitoring with echocardiography or stress tests is unnecessary on a routine basis. Because of the high frequency of accelerated atherosclerosis, however, any occurrence of dyspnea, dyspepsia, or shoulder or arm pain merits consideration of ischemic cardiac disease.
Differential Diagnosis
The differential diagnosis of lupus involves two linked questions: does the patient have a rheumatic disease, and if so, which one?
Nonrheumatic illnesses that mimic sle
The syndrome of fever, cytopenia, rash, and adenopathy suggests many infections, including HIV, cytomegalovirus, mono-nucleosis, and bacterial endocarditis. Acute polyarthritis, rash, and cytopenias can result from many viral infections, such as hepatitis, parvovirus, and rubella. These syndromes resolve spontaneously within several weeks. This syndrome also suggests hematologic malignancies, primarily the lymphomas, leukemias, and myelodysplastic syndromes. Although the presence of anti-nuclear antibody is common in many of these illnesses, the presence of anti-DNA or anti-Sm antibodies is not; also uncommon are the specific rashes of lupus, nephritis, and vascular manifestations such as periungual telangiectasia and vasculitic papules. Photosensitivity and frontal alopecia are also characteristics of lupus that do not occur in these other illnesses.
Non-SLE causes of nephritis include poststreptococcal glo-merulonephritis, Goodpasture disease, genetic nephropathies, and toxemia. The rash of rosacea is commonly mistaken for that of lupus. ITP or autoimmune hemolytic anemia may occur as isolated illnesses or as part of the multisystemic involvement of lupus. In these circumstances, full clinical and serologic evaluation for lupus will place the findings in proper context.
Rheumatic illnesses that resemble sle
Lupus may resemble a variety of other rheumatic diseases [see Table 1]. These include rheumatoid arthritis and Sjogren syndrome [see 15:II Rheumatoid Arthritis], as well as scleroderma [see 15:V Scleroderma and Related Diseases]. The polyarthritic presentation of lupus is very similar to that of rheumatoid arthritis, Lyme disease, and other rheumatic illnesses. Early scleroderma often presents with bilateral hand edema that is mistaken for polyarthritis.
Dermatomyositis [see 15:VI Idiopathic Inflammatory Myopathies] peaks in three age groups: 5 to 10 years of age, late teens and early 20s, and older than 45 years. The rash of dermatomyositis is similar to that of lupus, but they tend to involve the eyes differently: in dermatomyositis, telangiectasia causes the so-called heliotrope appearance of the eyelids; lupus rashes involve the eyebrows, but the malar rash stops abruptly at the orbits. Also, the rash in dermatomyositis commonly spares the ear canals, whereas the ear canals are commonly involved in lupus. Periungual telangiectasia is more dramatic in dermatomyositis than in lupus; it also occurs in scleroderma. Rash over the small joints of the hands suggests dermatomyositis; rash between the joints suggests lupus.
Compared with SLE, rheumatoid arthritis occurs in older persons (40 to 60 years of age) and has less of a female predominance (2:1 to 3:1). Although morning stiffness, fatigue, and weight loss are common in patients with rheumatoid arthritis, specific visceral multisystem disease is not. Leukocytosis rather than leukopenia is characteristic of rheumatoid arthritis. Renal disease is very rare, and when it does occur, it is attributable to tubular disease or amyloidosis rather than to glomerulonephri-tis. High fever does not occur in rheumatoid arthritis. From 10% to 20% of patients with rheumatoid arthritis have antinuclear antibodies; a small percentage have low-titer anti-DNA antibodies, and a minority have anti-SS-A and anti-SS-B antibodies. Complement levels are usually elevated. Rheumatoid factor is present in 80% of patients with rheumatoid arthritis, compared with its presence in 25% of lupus patients.
Overlap disease
Some patients have symptoms suggestive of lupus (most commonly, arthritis, pleuritic pain, and cytopenia) but lack the specific diagnostic criteria for lupus (e.g., butterfly rash, glomeru-lonephritis, and high-titer anti-DNA or anti-Sm antibody). Other patients have lupuslike symptoms together with findings suggestive of rheumatoid arthritis, dermatomyositis, or scleroderma. Patients with no definable serology and a nondescript clinical picture are defined as having undifferentiated connective tissue disease (UCTD). Still other patients have inflammatory myositis, Raynaud phenomenon, and sclerodactyly together with very high titer antibodies to the ribonucleoprotein antigen (U1 RNP) and no anti-DNA or anti-Sm antibody. This set of findings is defined as mixed connective tissue disease (MCTD).
The differentiation of SLE from UCTD, MCTD, and Sjogren syndrome depends on the extent and pattern of different organ involvement (glomerulonephritis is rare in all these disorders except lupus) and on the accompanying serologic abnormalities. High-titer anti-DNA antibody or anti-Sm antibody generally indicates lupus; high-titer anti-RNP antibody with no other positive antibodies indicates MCTD; and anti-SS-A and anti-SS-B antibodies are consistent with Sjogren syndrome but occur in lupus and rheumatoid arthritis, as well. Occasionally, patients have characteristic rheumatoid destructive arthritis, subcutaneous nodules, and high-titer rheumatoid factor and anti-DNA antibody. These patients, as well as those with other overlap features, should be treated as if they have both diseases.
The prognosis in patients with UCTD tends to be more benign than that in patients with SLE. Patients with MCTD do not develop glomerulonephritis, but the long-term prognosis for patients with this disorder is worsened by the eventual development of pulmonary hypertension.
Treatment
Acute disease
Management recommendations for the acute symptoms of lupus depend on the severity and organ systems involved. Non-life-threatening manifestations, such as minor arthritis, arthralgia, malaise, myalgias, serositis, and low-grade fever can often be controlled with full doses of NSAIDs. There is no specific preference among the NSAIDs, but lupus patients are unusually susceptible to hepatic and renal toxicities, which must be monitored. Also, in rare cases, lupus patients have developed abrupt high fever and meningitis after taking ibuprofen and similar drugs. Patients who do not respond to NSAIDs usually do respond to low doses (5 to 10 mg/day) of prednisone. As a rule, patients with inflammatory rashes, as well as patients anticipated to be on treatment for months or longer, should receive anti-malarial therapy with hydroxychloroquine, 200 mg twice daily. Over a course of 3 months or more, hydroxychloroquine reduces arthralgia, myalgia, rash, fatigue, malaise, and similar symp-toms.55 Patients expected to take corticosteroids for more than a few weeks should strongly consider bone-protective measures (see Osteoporosis, below). Such patients should also consider the addition of a lipid-lowering agent, such as a statin, to the regimen. Facial rashes, especially erythematous lesions with edema or telangiectasia, may respond to topical therapy with cortico-steroid creams.
Alopecia may recover spontaneously, but it is not otherwise easily amenable to therapy. Wigs and falls or hair extenders are useful. Skillful use of makeup can cover most pigment changes caused by discoid lupus.
Low-dose corticosteroid therapy may be appropriate for modest thrombocytopenia or anemia. Leukopenia does not usually require treatment. High-dose corticosteroid therapy (60 mg of prednisone daily) is used for patients with severe systemic symptoms, renal disease, or other visceral disease that is potentially life threatening. Treatment should be initiated in split doses during the day, maintained for 4 to 6 weeks, and then tapered; too early reduction of dose usually results in recurrence of disease activity. If longer-term use of corticosteroids is anticipated, if vasculitis or life-threatening disease is present, or if cortico-steroid toxicity is unacceptable, it is generally advisable to add immunosuppressive therapy. Immunosuppressive agents used for lupus include cyclophosphamide administered orally or intravenously, azathioprine, and mycophenolate mofetil. A standard regimen for active lupus nephritis includes a high-dose cor-ticosteroid and intravenous cyclophosphamide. The cyclophos-phamide is given at a dosage of 1 g/m2 monthly for 6 months and then every 3 months for 2 years.
Acute cerebral symptoms (other than stroke) are usually treated with high-dose corticosteroids. Hallucinations and other psychotic symptoms respond to antipsychotic medications such as haloperidol, which is often administered in conjunction with corticosteroids. Because psychosis may also result from the use of a high-dose of a corticosteroid alone, withdrawal of cortico-steroids may be necessary in some cases. The distinction between so-called steroid psychosis and lupus psychosis is quite difficult. No single set of criteria distinguishes between the two; evidence of ongoing active lupus in other organ systems is an indication to treat the patient for lupus psychosis. Acute lupus episodes are often treated with bolus doses of a corticosteroid (usually, 1,000 mg of methylprednisolone administered by rapid I.V. infusion [1 hr] once daily for 3 days). Very few formal studies support this practice, but clinical experience suggests its efficacy and relative safety. Bolus corticosteroid treatment may cause abrupt increases in blood pressure, acute vasospasm leading to stroke, cardiac infarct, or intestinal infarct. Transient oli-guria and increased serum creatinine levels may also occur. To prevent these complications, bolus therapy should be monitored closely and withheld if hypertension is not controlled. Access to renal replacement therapy must be available in the event that the patient experiences diminished renal function.
Many new therapies are being investigated. These are largely biologic therapies and include the use of drugs directed against receptors of immune-activating cells or recognition cells and the use of modulators of immune response, such as CD154, CTLA-4, and anti-C5b. Removal of antibody by passing patient plasma over an absorptive column is also being studied. Tumor necrosis factor-a (TNF-a) inhibition, which was once thought to be dangerous for SLE patients, is under reconsideration. Attempts at hormone manipulation, as with dehydroepiandrosterone (DHEA), have had only modest success.
No single test informs the physician whether treatment for acute SLE is successful or not. Instead, it is necessary to monitor the entire clinical picture, including symptoms and results of physical examination, routine laboratory tests, and immune function studies.
Indices of disease severity Flare
Increase of inflammation in any SLE-affected organ system is known as flare. In a subpopulation of SLE patients, flare is a continuous, not a dichotomous, variable. In a given patient, it may occur in different organ systems at different rates and intensities; for instance, rash may become severe while nephritis remains stable. As a result, several different schemas for measuring flare exist. They differ in giving different weights to individual measures of disease activity (for instance, does new nephritis count more or less than new rash?) and whether serologic measures (antinuclear antibody titer, anti-DNA antibody, complement) do or do not count in the determination. The available indices—SLE Disease Activity Index (SLEDAI), Systemic Lupus Activity Measure (SLAM), and British Isles Lupus Assessment Group (BILAG)56— generally agree in identifying flare in populations of patients but often disagree in specifics. There is poor consensus about distinguishing between day-to-day variation of disease activity and a definite flare. Several components of the indices (e.g., quantita-tion of rash or of arthritis) are sufficiently subjective that investigators in clinical trials must undergo standardization training before they can validate their scores on individual patients.
Flare in pregnancy Proteinuria, thrombocytopenia, and other pregnancy events that occur in the absence of lupus invalidate most scoring systems for pregnant patients. A specific instrument, the SLE Pregnancy Disease Activity Index (SLEPDAI), has been devised for use in pregnant patients.57
Damage
Recurring inflammation and vascular occlusion induce irreversible scarring and such permanent deficits as stroke, cataract, skin thinning, osteoporosis, osteonecrosis, and renal failure. It is common practice, therefore, to score SLE patients according to their activity (flare) indices and their damage indices. The most widely used damage index is the Systemic Lupus International Collaborating Clinics (SLICC).58
Sle during pregnancy
Pregnancy in patients with SLE, once thought to be contraindi-cated, is now a routine event. The complications of pregnancy in these patients are related to three major issues: abnormal renal function, the presence of antiphospholipid antibody, and the presence of anti-SS-A and anti-SS-B antibody. It remains debatable whether lupus is exacerbated by pregnancy, but consensus now exists that pregnant SLE patients do not need prophylactic increases of corticosteroid therapy; rather, they should be treated in the same manner as patients who are not pregnant, except that drugs with fetal toxicity should not be given.
Renal disease, particularly renal insufficiency, strongly predisposes to toxemia of pregnancy. Hypertension, reduced creati-nine clearance, and active SLE all threaten the viability of the fetus. Conversely, women who enter pregnancy with no renal disease and no hypertension usually do well. Recurrent pregnancy loss, particularly in the second trimester, is one of the prime clinical manifestations of the antiphospholipid antibody syndrome; for antiphospholipid antibody-positive patients, the peripartum period is one of high risk for thromboembolic disease. Women who have antibody to the SS-A or SS-B antigen are at risk of delivering children with the neonatal lupus syndrome.
Chronic disease and complications
The major treatment issue for long-term lupus patients is the prevention or management of damage to the arteries, kidneys, bones, and brain rather than the control of immune response and inflammation. The physician must anticipate chronic effects of both the disease and its therapy.
During treatment with high-dose corticosteroids, with or without immunosuppressive agents, avoidance of infections is a primary concern. Herpes zoster, tuberculosis, and a variety of bacterial infections are the primary threats. Pneumocystis jiroveci (formerly Pneumocystis carinii) infection is seen relatively infrequently; most rheumatologists do not routinely suggest prophylaxis against this organism. Complications of long-term cortico-steroid therapy include osteoporosis (see below) and cataracts, cutaneous striae, cutaneous hemorrhage, diabetes, and oral and vaginal candidiasis. In patients with long-standing disease, these complications produce as much morbidity as the disease itself.
Antiphospholipid Antibody Syndrome
Treatment of antiphospholipid antibody syndrome is antico-agulation to an international normalized ratio (INR) of 2.0 to 3.0. Warfarin and low-dose aspirin are used to prevent thrombotic manifestations of the syndrome; heparin or low-molecular-weight heparin is used in pregnant patients.59 Recent data suggest that the addition of statin drugs, to downregulate endothe-lial activation, may also be of benefit.60
Atherosclerosis
Early-onset, severe atherosclerosis is a common problem in patients with long-standing SLE. Atherosclerosis most commonly presents as coronary and cerebral artery occlusion; peripheral vascular occlusion also occurs. The cause is unknown, but chronic inflammation, corticosteroid therapy, uncontrolled hypertension, diabetes, smoking, and other factors have been implicated. Most specialists in this area recommend early and vigorous treatment of known risk factors in all lupus patients. The atherosclerosis of lupus is managed in the same manner as atherosclerosis in other situations, except that vascular interventions in patients with antiphospholipid antibody syndrome are hazardous.
Osteonecrosis
Although the mechanism of osteonecrosis is not clearly known, many authorities believe that a steroid-induced increase in the volume of lipocytes increases pressure in the bone marrow, cutting off blood flow to the vulnerable areas. Consequently, if osteonecrosis is recognized before the joint has collapsed (usually by bone scan or MRI), trephining the bone to reduce in-traosseous pressure (so-called core decompression) has been recommended. However, the validity of this theory and the efficacy of the treatment remain unproved. Usually, joint replacement is eventually required.61
Osteoporosis
Osteoporosis follows long-term corticosteroid therapy with sufficient frequency that all patients receiving such therapy should receive prophylaxis for this complication. High-dose oral calcium (i.e., 1,500 mg daily), vitamin D, a bisphosphonate drug, and parathyroid hormone are the primary preventive measures; estrogen replacement may be considered in postmenopausal women who do not have antiphospholipid antibody. Weight-bearing exercise should be encouraged. Other prophylactic measures, including calcitonin and parathyroid hormone, may be appropriate. Because lupus patients are photosensitive, increased sun exposure to prevent osteoporosis is unwise. Bisphos-phonates should not be used in women anticipating pregnancy.
Cardiac Disease
Inflammatory cardiomyopathy responds to corticosteroids; is-chemic cardiomyopathy does not. Valvular insufficiencies and thromboemboli are late complications of lupus cardiac disease. Bacterial endocarditis rarely complicates this abnormality. Valvulitis generally does not respond to treatment, although it has been reported that acute valvulitis will respond to cortico-steroid therapy.62 Small numbers of patients require valve replacement, usually of the aortic or mitral valve. The mechanism of valvulopathy in SLE is unknown, as are methods of prevention.
Palliative care
A common mistake in the treatment of SLE is to assume that a given complaint reflects ongoing inflammatory disease, rather than irreversible damage, and that it can be controlled with anti-inflammatory and immunosuppressive therapy rather than with palliation. Examples of such symptoms include seizures, dementia, and other neurologic syndromes associated with brain in-farcts; cutaneous ulcers caused by long-standing vascular insufficiency; embolic phenomena from atherosclerosis; respiratory insufficiency from pulmonary fibrosis or pulmonary hypertension; arthritis from osteonecrosis, erosive rheumatoid-like arthritis, or tendinosis; and progressive renal insufficiency from arteri-olonephrosclerosis, interstitial fibrosis, or glomerulosclerosis.
Dementia
Chronic neurologic disease, often in the form of dementia, is a long-term sequela of SLE. Some causes are stroke (atherosclerotic, hypertensive, or thrombotic associated with antiphospholipid antibody), autoantibody attack on specific brain targets, small vessel occlusive disease, and drugs. Occasionally, patients are severely disabled. No effective prophylaxis is known.
Renal Failure
Patients with renal disease often need angiotensin-converting enzyme inhibitors for proteinuria, antihypertensives for hypertension, erythropoietin for anemia, and diuretics for edema. Renal failure in lupus occurs in three modes. In the first, acute inflammatory nephritis is characterized by distinctly abnormal uri-nalyses and clinically and serologically evident disease activity. Patients with this type of renal picture have rapidly rising serum creatinine levels and enter renal failure early after diagnosis. If treated aggressively, with high-dose corticosteroids and im-munosuppressive drugs, renal failure will be reversible in approximately one third of these patients.63 In the second mode of renal failure, which occurs only occasionally, patients will have renal failure from drug toxicity—usually NSAIDs—or acute tubular necrosis. Other manifestations of SLE are modified in uremia: rash is less prominent; and fever, cachexia, mucosal ulcers, and cytopenias are more prominent.
In the third mode, which is the most common, lupus patients enter renal failure slowly after many years of disease. Characteristically, at the time renal failure first appears, the patient has little systemic illness and has had months to years of modest renal insufficiency (with creatinine clearance at 10 to 30 ml/min and serum creatinine below 3.5 mg/dl), slowly rising serum creati-nine levels, relatively noninflammatory urinary sediments, and progressive anemia. Then, over a few months, the patient develops hypertension and fluid retention with or without cardiac failure. Abdominal pain is frequently present. Ultrasound shows small, fibrotic kidneys or thin, scarred renal cortices. Renal failure is only transiently reversible in such patients. Aggressive im-munosuppressive therapy is not helpful at this stage; on the contrary, it may hasten renal deterioration and will complicate initiation of dialysis.
Less commonly, renal failure is caused by antiphospholipid antibody-associated thrombotic microangiopathy. In these cases, the presentation comprises modest proteinuria with bland urine sediment and slowly rising serum creatinine levels, often with moderate hypertension. Lupus vasculitis involving the kidneys tends to be abrupt in onset, with severely abnormal urinalyses, severe hypertension, and rapidly progressive renal failure. This complication is treated with high-dose corticosteroids and im-munosuppression. However, full recovery is uncommon.
Lupus patients, particularly those who enter renal failure slowly, tolerate dialysis and renal transplantation well. However, preexisting cardiac, cerebral, and osteoarticular damage may be limiting factors. Patients who enter renal failure acutely often have other active systemic disease, with seizures and cytopenias being the most common. The common belief that lupus becomes inactive in renal failure is likely not true. Rather, in the majority of patients who enter dialysis, the lupus was already inactive sys-temically and remains so; probably, the renal failure results not from continuing disease but from progressive scarring. In the minority of patients who enter renal failure during an acute systemic flare, usually early in the course of the illness, active systemic disease tends to continue, and it represents a relative contraindication to renal transplantation. Patients on dialysis who have active SLE usually have high anti-DNA antibody levels and low complement levels. They respond to corticosteroid therapy, usually at lower doses than patients who are not on dialysis.
Prognosis
Prognosis in SLE has four elements: immediate prognosis for life, immediate prognosis for individual organ systems, and long-term prognosis for organ systems and for life.
During the early phases of lupus, complete reversal of almost all manifestations (i.e., rash, arthritis, fever, cytopenias, and nephritis) with aggressive therapy is expected. Exceptions include the scarring discoid rash, brain or spinal cord infarcts, and severe nephritis or nephrosis. In rare cases (< 5%), patients have such severe disease that despite treatment, they rapidly progress to death within 2 years. Because most newly diagnosed patients respond to therapy, 5-year survival is 80% to 90%, 10-year survival is 70% to 90%, and 20-year survival is nearly 70%.6 Determinants of survival are age, renal disease, and race, with African Americans having lower overall survival than whites.64
One organ system (e.g., kidneys or platelets) may fail to respond completely to treatment but not directly threaten the patient’s life. Such patients may be monitored without intervention. A patient may develop chronic renal insufficiency (e.g., serum creatinine, 3.0 mg/dl) or have persistent thrombocytope-nia (platelet count, 30,000/mm3) and be considered to be in remission and in no need of treatment.
Long-term prognosis is a function of organ damage from either SLE or its treatment. Pulmonary fibrosis and pulmonary hypertension respond poorly to therapy, although new protocols, such as bosentan or infusion of prostacyclin, may be useful for pulmonary hypertension. Patients with cardiopulmonary failure who have no other system disease limitations are candidates for heart and lung transplantation. Lupus patients with renal failure are candidates for dialysis and for renal transplantation.
