implanted on the leaßets previously deformed by LibmanÐSacks endocarditis.

Nervous System

Central nervous system involvement is the second most frequent SLE-related cause of death (after renal involvement) [197]. The most common neurological manifestation is psychiatric illness (organic brain syndrome) characterized by impairment of orientation, perception, memory, and intellectual function [198]. The second most common is seizures, especially grand mal seizure; petit mal, psychomotor epilepsy, temporal lobe epilepsy, and Jacksonian seizures may also appear. Seizures may be present at the time of diagnosis or later in the course of the disease, but in most cases they occur along with clinical and laboratory evidence of severe systemic disease. SLE patients with central nervous system disease (organic brain syndrome or seizures) are more likely to have evidence of vasculitis of other systems than those without central nervous system Þndings [197]. Chorea, recurrent headaches, hemiparesis, and cerebellar signs may occur along with other manifestations of the disease during an exacerbation. Cranial nerves, such as the ophthalmic, trochlear, abducens, and less commonly the trigeminal and facial, may be involved in episodes of active systemic disease when evidence of vasculitis is present in other systems [198]. Peripheral neuropathy occurs in about 14% of patients. The most common abnormality is sensory, although occasionally a sensorimotor disturbance may be seen [197]. Psychological abnormalities, such as depression and less often anxiety, are reactions to the disease and to the disÞgurement caused by both the disease and the corticosteroid therapy [198].

Lung

Pleuropulmonary manifestations, which occur in 50Ð75% of SLE patients, include pleurisy with or without effusion, acute pneumonitis, and diffuse interstitial pneumonitis [199, 200]. Pleural effusions in SLE are exudates with more than 3.0 g of protein per 100 ml, more than 55 mg/100 ml of glucose, and occasional lupus erythematosus (LE) cells; pleuritic pain is the usual complaint.

Acute pneumonitis may present with dyspnea and, less often, cough or hemoptysis as symptoms, and diffuse acinar inÞltrates, especially in the lung bases, as chest X-ray Þndings; lung function studies may reveal hypoxemia. Diffuse interstitial pneumonitis diagnosis is based on the symptom of dyspnea on exertion, physical Þndings of poor diaphragmatic movement and decreased resonance to percussion over the bases, and radiographic evidence of persistent, diffuse interstitial inÞltrates; lung function studies reveal a restrictive pattern. Pulmonary involvement may occur in SLE patients with no dyspnea and no radiographic abnormalities; the only disturbance in these patients is an impairment in the diffusion capacity.

Miscellaneous

Gastrointestinal symptoms, such as anorexia, nausea, vomiting, dysphagia, or abdominal pain, may occur in SLE patients and may mimic an acute surgical abdomen. Acute pancreatitis may result from active SLE or glucocorticoid therapy. Elevated serum levels of liver enzymes are common in active SLE, but they return to normal with response of the disease to therapy [201]. Slight- to-moderate splenomegaly may occur in 20% of SLE patients; lack of splenic activity is uncommon [202]. Lymph nodes are enlarged in 50% of SLE patients at the time of clinical disease activity. The parotid gland may also be enlarged during periods of active SLE [189].

6.1.2.3 Ocular Involvement

The ocular manifestations in SLE are important because they may be the initial manifestation of the disease or may serve as a barometer of the severity and prognosis of the systemic involvement. Unlike other collagen diseases, which have a frank predilection for either anterior or posterior segment involvement, SLE may affect every structure of the eye [203]. Any patient who develops retinal vasculitis and scleritis must be carefully studied for SLE.

Scleritis

The reported incidence of SLE in patients with scleritis is about 1% [122, 123]. The presence of

scleritis is a reasonably accurate guide to the systemic activity in a patient with SLE; the scleritis attacks become more severe and recurrent as the systemic disease deteriorates. Occasionally, scleritis may be the initial manifestation of SLE [123]. SLE scleritis generally takes the form of diffuse anterior scleritis or nodular anterior scleritis, but necrotizing anterior scleritis may also occur, especially when systemic vasculitic lesions become signiÞcant [123, 204]. Posterior scleritis, although uncommon, may also be an SLE manifestation [205]. Any patient who presents with any type of scleritis should be screened for SLE; scleritis resolves with adequate control of systemic disease. Scleral inßammation in SLE may extent to the adjacent structures and may cause keratitis and anterior uveitis. Although anterior uveitis is an unusual isolated Þnding in SLE (reported incidence of uveitis in patients with SLE ranges from 0.5 to 1.6%) [206], its incidence increases with the presence of SLE scleritis.

In our own series of 500 patients with scleritis, ten patients had SLE (2%); of those, four patients (40%) had bilateral scleritis. All patients were women with a mean age of 45.8 years (range, 24Ð69 years). Eight patients had diffuse anterior scleritis, one patient had nodular anterior scleritis, and one patient had posterior scleritis. The mean time of presentation of scleritis was 6 months after the SLE diagnosis. In most cases, scleritis appeared at the time of exacerbation of the systemic disease. In two cases, scleritis (posterior and diffuse) was the initial manifestation whose study led to the diagnosis of SLE. Three of ten patients (30%) with SLE scleritis had had at least one episode of anterior uveitis; all three had diffuse anterior scleritis. Two patients had keratitisassociated scleritis: one had peripheral corneal thinning and another had PUK. A decrease in visual acuity (equal to or greater than two Snellen lines at the end of the follow-up period or vision equal to or worse than 20/80 at the Þrst examination) occurred in 10% of the patients.

Episcleritis

Although episcleritis may occur in patients with SLE, the incidence is low. In the Watson and Hayreh [122] series of 159 patients with

episcleritis, there were no patients with SLE. Conversely, three studies reported the incidence of episcleritis in patients with SLE as 0.5, 1.9, and 1.1% (1 of 200 SLE patients, 2 of 105 SLE patients, and 1 of 94 patients, respectively) [123, 207, 208]. Occasionally, episcleritis may be the Þrst manifestation of SLE [209]. In our own series of 85 patients with episcleritis, no patients had SLE.

Other Ocular Findings

Aside from scleritis and episcleritis, anterior segment involvement in SLE may include conjunctivitis, keratitis, and anterior uveitis. Conjunctivitis may affect bulbar, fornix, and tarsal regions and may eventually leave subepithelial Þbrosis with shrinkage of the conjunctiva. Although superÞcial punctate keratitis is the most common corneal problem, stromal inÞltration, peripheral ulceration, and vascularization may also occur [210Ð213]. KCS may be associated with SLE (SjšgrenÕs syndrome), but its incidence is low [214Ð217]. Anterior uveitis may rarely occur in the absence of other ocular lesions [204, 206]. Although anterior uveitis may cause secondary glaucoma, it is never severe and responds well to adequate therapy. Posterior segment involvement is more common and serves as a better barometer of the severity of the disease than do anterior segment manifestations. The most frequent posterior segment manifestations include cottonÐwool spots, retinal hemorrhages, retinal edema, and optic disk edema; other reported fundus changes include retinal hard exudates, retinal vasculitis, central retinal vein occlusion, arteriolar narrowing, arteriovenous crossing changes, macular pigmentary mottling, and retinal scarring [206]. Although some of these manifestations may be a reßection of a hypertensive retinopathy, they may appear as independent signs as well; in cases of associated hypertension, the decision as to whether the retinal lesions are secondary to high blood pressure or to SLE immunological abnormalities may be difÞcult; the presence of anterior segment manifestations, such as scleritis or episcleritis, may be helpful in this regard because they are reßections of the disease process. Several authors have emphasized that the presence of