PATHOLOGY.

Few unique pathologic features are associated with SLE. In patients with arthritis, the synovial histopathology tends to be non-specific, with superficial fibrin-like material and local or diffuse cell lining proliferation. Vascular changes include perivascular mononuclear cells, lumen obliteration, enlarged endothelial cells, and thrombi, but fibrinoid necrosis is uncommon. Biopsies of the malar erythema may reveal some minor basal layer abnormalities, as well as immune complex deposits at the dermal-epidermal junction. Discoid skin lesions are characterized by hyperkeratosis, follicular plugging, and more basal cell layer changes, including immune complexes at the dermal-epidermal junction. Pleura and pericardium are infiltrated by mononuclear cells. Lupus pneumonitis is characterized by alveolar wall injury, hemorrhage, and edema; hyaline membrane formation; and immune complex deposits. Coronary arteries often demonstrate premature-onset atherosclerosis. Libman-Sacks endocarditis is characterized by the accumulation of immune complexes, mononuclear cells, hematoxylin bodies, and fibrin and platelet thrombi. Pathologic examination of the spleen often reveals an "onion skin" appearance of the splenic arteries, which is thought to represent healed arteritis.

RENAL DISEASE.

Minimal disease (type IIA mesangial disease) of glomeruli has immune complex deposits only in mesangial cells. Type IIb mesangial nephritis also has mesangial hypercellularity. Focal proliferative nephritis (type III) has segmental proliferation in glomerular tufts and in the mesangium and immune complex deposits in the mesangium and scattered granular deposits in the subendothelial, subepithelial, and intrabasement GBM. Active diffuse proliferative glomerulonephritis (type IV) affects more than 50% of glomeruli with cellular proliferation, necrosis, "wire loops," subendothelial deposits, and hematoxylin bodies. When chronic, the process involves sclerosis, adhesions, crescents, and (tubular) atrophy. Extensive "lumpy and bumpy" deposits of immune complexes are present. In membranous nephritis (type V) diffuse, uniform thickening of the GBM is seen, with a fine granular deposition of immune complexes in the subendothelial region beneath fused foot processes. Tubular degenerative changes with interstitial mononuclear cells are not uncommon. Extensive crescent formation, representing scarring, indicates a poor prognosis.

The brain is notable for the paucity of pathologic changes. Some minor blood vessel abnormalities, an occasional microinfarct, and some perivascular infiltration have been noted.

CLINICAL MANIFESTATIONS.

SLE is highly variable in onset as well as course. The initial symptoms may be non-specific(Table 289-4)and include myalgia, nausea, vomiting, headaches, depression, easy bruising, or more specific symptoms or any combination thereof. These symptoms may be mild or severe, fleeting or persistent.

GENERAL SYMPTOMS.

Fatigue occurs in virtually all patients with SLE. Fatigue may parallel the onset of SLE or its relapse but should be distinguished from the fatigue associated with other factors such as increased workload, sleep disturbance, depression, unhealthful habits, stress, deconditioning, anemia, the use of certain

medications (including prednisone), and any intercurrent disease. Fever is seen in 80% of patients; it is usually episodic. Infections, which occur commonly in SLE patients, must always be considered.

MUSCULOSKELETAL MANIFESTATIONS.

Arthralgia and arthritis have been noted in 95% of patients with SLE. Symptoms tend to be asymmetrical and migratory, with complaints in a particular joint often gone in 1 to 3 days. Fingers, hands, wrists, knees, and less frequently, ankles, elbows, shoulders, and hips are affected. Morning stiffness is generally measured in minutes, in contrast to hours in rheumatoid arthritis. Although joint deformities are considered to be more a feature of rheumatoid arthritis, damage to periarticula