retinal lesions correlates with the systemic course of the disease [218Ð221]; RothÞeld [221] found an association between the presence of hard exudates and central nervous system disease activity (seizures and organic brain disease). Regan and Foster [222], however, think that localized manifestations of the disease (eye, skin, and kidney) may sometimes occur, and therefore that retinal vasculitis also may appear without exacerbation of SLE [222]. Whichever the case is, if a patient with SLE develops retinopathy, a thorough search for systemic evidence of disease activity must be performed promptly and, if positive, aggressive therapy must be instituted to control both systemic and ocular abnormalities. Central nervous system SLE vasculitis may produce ocular abnormalities, such as internuclear ophthalmoplegia, nystagmus, cranial nerve palsies (second, third, Þfth, sixth, or seventh nerve palsies), homonymous hemianopia, and papilledema [198, 223].

6.1.2.4 Laboratory Findings

Laboratory tests serve (1) to establish or rule out the diagnosis; (2) to follow the course of disease, particularly to suggest that a ßare is occurring or organ damage is developing; and (3) to identify adverse effects of therapies.

Diagnostically, the most important autoantibodies to detect are ANA since the test is positive in >95% of patients, usually at the onset of symptoms [224]. A few patients develop ANA within 1 year of symptom onset; repeated testing may, thus, be useful. ANA-negative lupus exists, but is very rare in adults and is usually associated with other autoantibodies (anti-Ro or anti-DNA). High-titer IgG antibodies to double-stranded DNA (dsDNA) (but not to single-stranded DNA) are speciÞc for SLE (Table 3.9). There is no international standardized test for ANA; variability between different service laboratories is high. Enzyme-linked immunosorbent assays (ELISA) and immunoßuorescent reactions of sera with the dsDNA in the ßagellate Crithidia luciliae have ~60% sensitivity for SLE; identiÞcation of high-avidity anti-dsDNA in the Farr assay is not as sensitive but may correlate better with risk for nephritis. Titers of anti-dsDNA vary over time. In some patients, increases in quantities of anti-dsDNA herald a ßare, particularly of

nephritis or vasculitis. Antibodies to Sm are also speciÞc for SLE and assist in diagnosis; anti-Sm antibodies do not usually correlate with disease activityorclinicalmanifestations.Antiphospholipid (aPL) antibodies are not speciÞc for SLE, but their presence fulÞlls one classiÞcation criterion and they identify patients at increased risk for venous or arterial clotting, thrombocytopenia, and fetal loss. There are two widely accepted tests that measure different antibodies (anticardiolipin and lupus anticoagulant): (1) ELISA for anticardiolipin (internationally standardized with good reproducibility) and (2) a sensitive phospholipid-based activated prothrombin time, such as the dilute Russell venom viper test. Some centers also recommend measurement of antibodies to b2 glycoprotein 1, a serum protein cofactor that is the target of most antibodies to cardiolipin and some lupus anticoagulants. High titers of IgG anticardiolipin (>50 IU) indicate high risk for a clinical episode of clotting. Quantities of aPL may vary markedly over time; repeated testing is justiÞed if clinical manifestations of the aPL antibody syndrome (APS) appear. Making a diagnosis of APS, with or without SLE, requires the presence of clotting and/or repeated fetal losses plus at least two positive tests for aPL, at least 12 weeks apart. An additional autoantibody test with predictive value (not used for diagnosis) detects anti-Ro, which indicates increased risk for neonatal lupus, sicca syndrome, and SCLE. Women with childbearing potential and SLE should be screened for aPL and anti-Ro.

Antibodies to coagulation factors VIII, IX, XI, or XII, to platelets, or to immunoglobulins (rheumatoid factor) also may occur in SLE patients; these abnormalities also may be seen in other diseases.

The presence of low serum complement [C3 and C4, or CH50 (total hemolytic complement)] levels coupled with the presence of anti-DNA antibodies is highly speciÞc for SLE [225]. Low serum complement levels, serum cryoglobulins, or serum immune complexes may correlate with exacerbation of the disease.

Urinalysis in active nephritis may show proteinuria, microscopic hematuria, and cellular casts; this test and the serum creatinine test should be done periodically in patients with SLE.