SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

ANA     Diagnostic Criteria     Renal Involvement     Drug Induced

Systemic lupus erythematosus is an autoimmune disease that occurs secondary to the production of autoantibodies to cellular nuclear components. This disease may present with a variety of different symptoms. SLE occurs mostly in young female patients, with a peak incidence between the ages of 15 and 40. African Americans and Hispanics are affected more frequently than Caucasians. The prevalence of this disease is approximately 1 in 2,000 individuals in the general population. There is a strong familial association with a very high frequency of disease occurrence in first-degree relatives of affected individuals. Drug-induced lupus is caused by a variety of drugs to include hydralazine, procainamide hydrochloride, isoniazid, thorazine, and methyldopa. Drug-induced lupus often resolves after discontinuation of the offending agent.

Symptoms include the following:

CUTANEOUS: Includes malar or discoid rashes, photosensitivity, painless oral ulcers, or alopecia. Microscopic examination of skin lesions reveals inflammation and degeneration at the dermal-epidermal junction. The basal or germinal layers are usually the primary site of injury.

RENAL: Involvement is frequent and is often discovered by demonstrating proteinuria of 500 mg/day (3+ on urine dipstick), the presence of urinary casts, hematuria, pyuria, or a rise in the serum creatinine. Renal biopsy is required for proper staging.

SEROSITIS: Commonly manifests as small exudative pleural effusions with normal glucose levels and the presence of LE cells. Pericarditis or posterior pericardial effusions are found less frequently.

GASTROINTESTINAL: manifests as nonspecific complaints such as diffuse abdominal pain, anorexia, nausea, or vomiting. Hepatomegaly is common but clinical liver disease is not. Transaminasitis may be seen during active disease but usually resolves with adequate treatment of the lupus flare.

NEUROPSYCHIATRIC: Symptoms often include intractable headaches unresponsive to narcotics. Seizure activity is common and may be either focal or generalized. Chorea is an early manifestation of SLE. Cerebrovascular accidents and subarachnoid hemorrhages are troublesome complications. Frank psychosis is often a manifestation of SLE and may be exacerbated by the use of steroids. If confusion exists as to whether the psychosis is steroid-induced, it is then prudent to stop steroid treatment. If the psychosis gets worse, it is secondary to the SLE; however, if it resolves, then it was steroid-induced. Cerebritis, neuropathy, and an acute ascending motor paralysis may all be complications of SLE.

PULMONARY: Common manifestations include pleuritis (resolves with NSAIDs or steroid therapy), pleural effusions (usually small exudative effusions with a normal glucose and LE cells), pulmonary emboli, pulmonary hemorrhage (often fatal), shrunken lung (secondary to diaphragmatic dysfunction), pulmonary hypertension, interstitial lung disease (characterized by a restrictive pattern with a decreased DLCO), and pneumonitis (characterized by ill-defined migratory infiltrates on chest radiograph).

MUSCULOSKELETAL: Arthritis and arthralgia are common manifestations. The arthritis is usually episodic, symmetric, and involving the small joints of the hands, wrist, and knees. Jacouds arthritis refers to a nonerosive but deforming arthritis with ulnar deviation, swan neck deformities, and subluxations. Avascular necrosis, usually of the femoral head, may occur secondary to SLE or steroid therapy.

CARDIAC: Complications may manifest as pericarditis, myocarditis, endocarditis, or coronary artery disease. Arrhythmias, conduction defects, and unexplained cardiomegaly or tachycardia should alert physicians to the possibility of underlying myocarditis. Libman-Sacks endocarditis refers to sterile verrucous vegetations on the mitral valve; however, they have become less common since steroid therapy has been used.

RETICULOENDOTHELIAL: Splenomegaly and lymphadenopathy are common manifestations. Lymph node biopsy reveals reactive hyperplasia.

SYSTEMIC: Fever, fatigue, and weight loss are common manifestations.

Laboratory abnormalities associated with SLE are numerous. The complete blood count may reveal leukopenia (particularly lymphopenia), normocytic anemia (may be secondary to chronic disease, renal insufficiency, or medications), hemolytic anemia (usually Coombs positive but may be negative), or thrombocytopenia. A normal PT with a prolonged aPTT or false-positive VDRL are indicative of possible underlying anticardiolipin antibodies or lupus anticoagulant. The complement levels either C3, C4, or CH50 are usually depressed. Complement levels are often studied chronically to detect lupus flares.

Tests more specific for the diagnosis of SLE include ANA (antinuclear antibodies), dsDNA (a positive test may indicate patients with a propensity toward aggressive lupus nephritis), and various antibodies against antigen complexes (Sm, RNP, SS-A, and SS-B). When interpreting the ANA test results, it is important to remember that the higher the titer, the more likely an autoimmune disease exists, that an elevated titer does not always mean the patient has lupus (false-positive elevations are seen in the elderly and female patients), and that certain conditions (pregnancy, psoriasis, malignant melanoma, ovarian carcinoma, prostatic cancer, sarcomas, leukemia, Hodgkins disease, Burkitts lymphoma, malaria, idiopathic pulmonary fibrosis, primary biliary cirrhosis, chronic active hepatitis, alcoholic liver disease, and end-stage renal disease patients on hemodialysis) are associated with an elevated ANA. The serum ANA will positive in 95% of cases of SLE; therefore, a negative test argues strongly against this diagnosis. Other tests more specific for the diagnosis of SLE (anti-Sm, anti-RNP, and anti-SS-B) should not be ordered in the face of a negative ANA. However, ANA-negative SLE does occur, and when SLE is still suspected in the face of a negative ANA titer, a decreased CH50 or a positive anti-Ro (SS-A) antibody will help confirm the diagnosis. Although these tests are quite helpful in establishing the diagnosis, systemic lupus erythematosus is a clinical diagnosis made when 4 of the 11 criteria established by the American College of Rheumatology are present. Antihistone antibody is indicative of drug-induced lupus (positive in over 90% of cases); however, this test may also be positive in patients with idiopathic SLE. Other indicators of drug-induced lupus, as opposed to SLE, include the following: antibodies to single-stranded DNA and normal complement levels

Current medications available for the treatment of SLE include NSAIDs, steroids, plaquenil, and belimumab. Treatment should be tailored to the individual patient, and in most cases it is prudent to obtain consultation from a specialist on rheumatic or renal diseases.