Renal Manifestations. Renal involvement eventually will affect up to 70% to 80% of all patients, but the clinical presentation varies and includes an abnormal urine sediment; nephritis, nephrotic syndrome; or acute or chronic renal insufficiency. Screening the urine for blood and protein is an essential part of each SLE patient’s rheumatology visit. Hematuria is usually microscopic. Granular and fatty casts reflect proteinuric states, whereas red blood cells casts or mixed (red and white) cell casts are seen in patients with glomerulonephritis. Renal damage varies as follows: class I—minimal lesions with deposition of immune complexes in the mesangium and seen by immunofluorescence, class II—mesangial hypercellularity, class III—focal lupus nephritis involving less than 50% of all glomeruli with focal subendothelial immune deposits, class IV—diffuse lupus nephritis characterized by diffuse segmental or global endocapillary or extracapillary glomerulonephritis involving more than 50% of the glomeruli, class V—membranous lupus nephritis with global or segmental subepithelial immune deposits. The end result of sustained, untreated renal inflammation is progression to class VI—advanced sclerotic lupus nephritis when 90% or more of the glomeruli are globally scarred.

For an accurate diagnosis, a renal biopsy specimen with 10 or more glomeruli is optimal.

Nervous System Manifestations. Both the central and peripheral nervous system can be affected in SLE. Neuropsychiatric syndromes in patients with SLE include aseptic meningitis, cerebrovascular disease, demyelinating syndromes, headaches, movement disorders, seizures, acute confusional states, cognitive dysfunction, mood disorders, and psychosis. Mononeuropathy, Guillain-Barré syndrome, autonomic disorders, myasthenia gravis, polyneuropathy, and plexopathy have also been reported. These conditions are seen also in patients without SLE; therefore, assigning them to lupus can be a major challenge for the clinician. Non–lupus-related causes such as infections, drugs, electrolyte abnormalities, primary psychiatric disorders, fibromyalgia, and atherosclerosis must be excluded. Vasculitis is rare, whereas a bland vasculopathy involving small vessels is the predominant finding in neuropathologic autopsy studies.

Cardiopulmonary Manifestations. Serositis (pleuritis, pericarditis) is the most common cardiopulmonary complication of lupus. Cardiac tamponade is rare. Myocardial involvement is rare and typically occurs in the setting of generalized SLE activity. SLE patients have an increased risk of death as a result of coronary heart disease and stroke. Diffuse thickening of the mitral and aortic valves, Libman-Sacks endocarditis, valvular insufficiency, and stenosis occur with decreasing frequency. Acute pneumonitis, pulmonary embolism, and alveolar hemorrhage present as acute respiratory symptoms, cough, and dyspnea. Alveolar hemorrhage is an emergency, and these patients should be immediately admitted to a hospital and undergo bronchoscopy while high-dose corticosteroid therapy is initiated. Hemoptysis may be absent; the sole clues to the diagnosis may be a drop in hemoglobin, shortness of breath, and bilateral infiltrates on a chest radiograph.

Patients with chronic shortness of breath and dry cough should be evaluated for interstitial lung disease and isolated pulmonary hypertension.

Pregnancy in Lupus. Although fertility is not affected by SLE, there is an increased frequency of midtrimester spontaneous abortions, prematurity, and stillbirth. Lupus activity at the time of conception is a predictor of pregnancy outcome.

The use of estrogens in women with active SLE is contraindicated, while their ability to increase flares in stable SLE patients is debated.

Neonatal lupus syndrome may present as rash, transient thrombocytopenia, and complete heart block, which is often irreversible. Screening for complete heart block should be performed in all fetuses whose mothers are positive for IgG anti-Ro/SSA antibodies. These antibodies are able to cross the placenta and injure an otherwise normally developing heart.

LABORATORY TESTING

Antinuclear antibodies are the most sensitive screening test for SLE, but the specificity of this test is very low for SLE. A negative ANA test argues strongly against SLE.