The systemic features include fever, anorexia, malaise, and weight loss. Most patients have skin lesions at some time; the characteristic “butterfly” (malar) rash affects less than half of patients. Other cutaneous manifestations are panniculitis (lupus profundus) (eFigure 20–13), discoid lupus and typical fingertip lesions (periungual erythema, nail fold infarcts, and splinter hemorrhages). Alopecia is common. Mucous membrane lesions tend to occur during periods of exacerbation. Raynaud phenomenon, present in about 20% of patients, often antedates other features of the disease.
Lupus panniculitis (also known as lupus profundus) in a patient with systemic lupus erythematosus. (Used, with permission, from Nicole Richman, MD.)
Joint symptoms, with or without active synovitis, occur in over 90% of patients and are often the earliest manifestation. The arthritis can lead to reversible swan-neck deformities, but radiographic erosions and subcutaneous nodules are rare.
Ocular manifestations include keratoconjunctivitis sicca and retinal vasculopathy (cotton-wool spots, episcleritis, scleritis and optic neuropathy). Pleurisy and pleural effusion are common. Pneumonitis, interstitial lung disease, and pulmonary hypertension can rarely occur. Alveolar hemorrhage is uncommon but life-threatening.
The pericardium is affected in the majority of patients. Heart failure may result from myocarditis and hypertension. Cardiac arrhythmias are common. Atypical verrucous endocarditis of Libman-Sacks is usually clinically silent but occasionally can produce acute or chronic valvular regurgitation—most commonly mitral regurgitation.
Mesenteric vasculitis occasionally occurs in SLE and may closely resemble polyarteritis nodosa, including the presence of aneurysms in medium-sized blood vessels. Abdominal pain (particularly postprandial), ileus, peritonitis, and perforation may result.
Neurologic complications of SLE include psychosis, cognitive impairment, seizures, peripheral and cranial neuropathies, transverse myelitis, and strokes. Severe depression and psychosis are sometimes exacerbated by the administration of large doses of corticosteroids.
Several forms of glomerulonephritis may occur, including mesangial, focal proliferative, diffuse proliferative, and membranous (see Chapter 22). Some patients may also have interstitial nephritis. With appropriate therapy, the survival rate even for patients with serious kidney disease (proliferative glomerulonephritis) is favorable, albeit a substantial portion of patients with severe lupus nephritis develop end-stage renal disease.
Hematologic manifestations include leukopenia, autoimmune hemolytic anemia, immune thrombocytopenia, and thrombotic thrombocytopenic purpura.
(Tables 20–7 and 20–8.) SLE is characterized by the production of many different autoantibodies. Antinuclear antibody tests based on immunofluorescence assays using HEp-2 cells (a human cell line) as a source of nuclei are nearly 100% sensitive for SLE but not specific—ie, they are positive in low titer in up to 20% of healthy adults and also in many patients with other immune-mediated conditions such as rheumatoid arthritis, thyroid disease, scleroderma, and Sjögren syndrome. False-negative results can occur with tests for antinuclear antibodies based on multiplex assays that use specific nuclear antigens rather than cell lines. Therefore, SLE should not be excluded on the basis of a negative multiplex assay for antinuclear antibodies. Antibodies to double-stranded DNA and to Sm are specific for SLE but not sensitive, since they are present in only 60% and 30% of patients, respectively. Depressed serum complement—a finding suggestive of disease activity—often returns toward normal in remission. Anti–double-stranded DNA antibody levels also correlate with disease activity in some patients; anti-Sm levels do not. Other autoantibodies commonly seen in SLE include antibodies to SS-A/Ro, SS-B/La, ribonucleoprotein (RNP), and phospholipid. Antibodies to SS-A/Ro are associated with subacute cutaneous lupus; during pregnancy these autoantibodies can cross the placenta and damage the developing fetal conduction system, producing congenital heart block.
Table 20–7.Frequency (%) of autoantibodies in rheumatic diseases.1 ||Download (.pdf) Table 20–7. Frequency (%) of autoantibodies in rheumatic diseases.1
| ||ANA ||Anti-Native DNA ||Rheumatoid Factor ||Anti-Sm ||Anti-SS-A ||Anti-SS-B ||Anti-SCL-70 ||Anti-Centromere ||Anti-Jo-1 ||ANCA |
|Rheumatoid arthritis ||30–60 ||0–5 ||70 ||0 ||0–5 ||0–2 ||0 ||0 ||0 ||0 |
|Systemic lupus erythematosus ||95–100 ||60 ||20 ||10–25 ||15–20 ||5–20 ||0 ||0 ||0 ||0–1 |
|Sjögren syndrome ||95 ||0 ||75 ||0 ||65 ||65 ||0 ||0 ||0 ||0 |
|Diffuse scleroderma ||> 95 ||0 ||30 ||0 ||0 ||0 ||33 ||1 ||0 ||0 |
|Limited scleroderma (CREST syndrome) ||> 95 ||0 ||30 ||0 ||0 ||0 ||20 ||50 ||0 ||0 |
|Polymyositis/dermatomyositis ||80 ||0 ||33 ||0 ||0 ||0 ||0 ||0 ||20–30 ||0 |
|Granulomatosis with polyangiitis ||0–15 ||0 ||50 ||0 ||0 ||0 ||0 ||0 ||0 ||93–961 |
Table 20–8.Frequency (%) of laboratory abnormalities in systemic lupus erythematosus. ||Download (.pdf) Table 20–8. Frequency (%) of laboratory abnormalities in systemic lupus erythematosus.
|Anemia ||60% |
|Leukopenia ||45% |
|Thrombocytopenia ||30% |
|Antiphospholipid antibodies || |
| Anti-cardiolipin antibody ||25% |
| Lupus anticoagulant ||7% |
| Anti-beta-2-glycoprotein 1 ||25% |
|Direct Coombs-positive ||30% |
|Proteinuria ||30% |
|Hematuria ||30% |
|Hypocomplementemia ||60% |
|ANA ||95–100% |
|Anti-double stranded DNA ||50% |
|Anti-Sm ||20% |
During disease flares, elevations in the ESR are common, but the serum CRP is usually normal unless there is serositis or arthritis. Abnormality of urinary sediment, including hematuria with or without casts, and proteinuria (varying from mild to nephrotic range) can indicate active lupus nephritis.