SYSTEMIC LUPUS ERYTHEMATOSUS
SLE is an inflammatory autoimmune disorder characterized by auto-antibodies to nuclear antigens. It can affect multiple organ systems. Many of its clinical manifestations are secondary to the trapping of antigen-antibody complexes in capillaries of visceral structures or to autoantibody-mediated destruction of host cells (eg, thrombocytopenia). The clinical course is marked by spontaneous remission and relapses. The severity may vary from a mild episodic disorder to a rapidly fulminant, life-threatening illness.
The incidence of SLE is influenced by many factors, including sex, race, and genetic inheritance. About 85% of patients are women. Sex hormones appear to play some role; most cases develop after menarche and before menopause. Among older individuals, the sex distribution is more equal. Race is also a factor, as SLE occurs in 1:1000 white women but in 1:250 black women.
Familial occurrence of SLE has been repeatedly documented, and the disorder is concordant in 25–70% of identical twins. If a mother has SLE, her daughters’ risks of developing the disease are 1:40 and her sons’ risks are 1:250. Aggregation of serologic abnormalities (positive antinuclear antibody) is seen in asymptomatic family members, and the prevalence of other rheumatic diseases is increased among close relatives of patients. The importance of specific genes in SLE is emphasized by the high frequency of certain HLA haplotypes, especially DR2 and DR3, and null complement alleles.
The diagnosis of SLE should be suspected in patients having a multisystem disease with a positive test for antinuclear antibodies. It is imperative to ascertain that the condition has not been induced by a drug.
Symptoms and Signs
The systemic features include fever, anorexia, malaise, and weight loss.
Most patients have skin lesions at some time; the characteristic “butterfly” (malar) rash affects less than half of patients. Other cutaneous manifestations are panniculitis (lupus profundus), discoid lupus, typical fingertip lesions, periungual erythema, nail fold infarcts, and splinter hemorrhages.
Alopecia is common. Mucous membrane lesions tend to occur during periods of exacerbation.
Raynaud phenomenon, present in about 20% of patients, often antedates other features of the disease.
Joint symptoms, with or without active synovitis, occur in over 90% of patients and are often the earliest manifestation. The arthritis can lead to reversible swan-neck deformities, but erosive changes are almost never noted on radiographs. Subcutaneous nodules are rare.
Ocular manifestations include conjunctivitis, photophobia, transient or permanent monocular blindness, and blurring of vision. Cotton-wool spots on the retina (cytoid bodies) represent degeneration of nerve fibers due to occlusion of retinal blood vessels.
Pleurisy, pleural effusion, bronchopneumonia, and pneumonitis are frequent. Restrictive lung disease can develop. Alveolar hemorrhage is uncommon but life-threatening. Interstitial lung disease is rare.
The pericardium is affected in the majority of patients. Heart failure may result from myocarditis and hypertension. Cardiac arrhythmias are common. Atypical verrucous endocarditis of Libman-Sacks is usually clinically silent but occasionally can produce acute or chronic valvular regurgitation—most commonly mitral regurgitation.
Mesenteric vasculitis occasionally occurs in SLE and may closely resemble polyarteritis nodosa, including the presence of aneurysms in medium-sized blood vessels. Abdominal pain (particularly postprandial), ileus, peritonitis, and perforation may result.
Neurologic complications of SLE include psychosis, cognitive impairment, seizures, peripheral and cranial neuropathies, transverse myelitis, and strokes. Severe depression and psychosis are sometimes exacerbated by the administration of large doses of corticosteroids.
Several forms of glomerulonephritis may occur, including mesangial, focal proliferative, diffuse proliferative, and membranous. Some patients may also have interstitial nephritis. With appropriate therapy, the survival rate even for patients with serious chronic kidney disease (proliferative glomerulonephritis) is favorable, albeit a substantial portion of patients with severe lupus nephritis still eventually require renal replacement therapy.
SLE is characterized by the production of many different autoantibodies. Antinuclear antibody tests based on immunofluorescence assays using HEp-2 cells (a human cell line) as a source of nuclei are nearly 100% sensitive for SLE but not specific—ie, they are positive in low titer in up to 20% of healthy adults and also in many patients with nonlupus conditions such as rheumatoid arthritis, autoimmune thyroid disease, scleroderma, and Sjögren syndrome. False-negative results can occur with tests for antinuclear antibodies based on multiplex assays that use specific nuclear antigens rather than cell lines.
Therefore, SLE should not be excluded on the basis of a negative multiplex assay for antinuclear antibodies. Antibodies to double-stranded DNA and to Sm are specific for SLE but not sensitive, since they are present in only 60% and 30% of patients, respectively.
Depressed serum complement—a finding suggestive of disease activity—often returns toward normal in remission. Anti–double-stranded DNA antibody levels also correlate with disease activity in some patients; anti-Sm levels do not.
Three types of antiphospholipid antibodies occur. The first is anti-cardiolipin antibodies (which includes antibodies that cause the biologic false-positive tests for syphilis); the second is the lupus anticoagulant, which despite its name is a risk factor for venous and arterial thrombosis and for miscarriage.
The lupus anticoagulant often causes prolongation of the activated partial thromboplastin time, and its presence is confirmed by an abnormal phospholipid-dependent clotting test, such as the Russell viper venom time (RVVT), that corrects with the addition of excess phospholipid but not normal plasma.
Antibodies to beta-2-glycoprotein 1 is the third type of antiphospholipid antibody. Abnormality of urinary sediment is almost always found in association with kidney lesions. Showers of red blood cells, with or without casts, and proteinuria (varying from mild to nephrotic range) are frequent during exacerbation of the disease.
Differential diagnosis includes drug-induced lupus, rheumatoid arthritis, systemic vasculitis, scleroderma, primary antiphospholipid syndrome, inflammatory myopathies, viral hepatitis, sarcoidosis, and acute drug reactions.
Treating SLE often requires a team approach because of the number of organs that can be affected.
SLE treatment consists primarily of immunosuppressive drugs that inhibit activity of the immune system. Hydroxychloroquine and corticosteroids (e.g., prednisone) are often used to treat SLE. The FDA approved belimumab in 2011, the first new drug for SLE in more than 50 years.
SLE also may occur with other autoimmune conditions that require additional treatments, like Sjogren’s syndrome, antiphospholipid syndrome, thyroiditis, hemolytic anemia, and idiopathic thrombocytopenia purpura.