Approach Considerations
The initial laboratory evaluation should include a complete blood count (CBC) with platelets and reticulocyte count; a complete chemistry panel to evaluate electrolytes, liver, and kidney function; urine analysis; and a measure of acute phase reactants (eg, erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]).
Diagnostic laboratory studies include ANA, anti–double-stranded DNA, anti-Smith antibody, lupus anticoagulant, and antiphospholipid antibody panel. [15] Obtain other autoantibodies, which may be associated with specific disease manifestations, including anti-Ro, anti-La antibodies associated with Sjögren syndrome, and antiribonucleoprotein (anti-RNP) antibodies.
In addition to anti–double-stranded DNA, complement levels, including total hemolytic complement, C3, and C4, are markers of disease activity and are found to be low in most patients with active disease. Initial assessment of quantitative immunoglobulins is useful, because patients with lupus often have hypergammaglobulinemia and have a higher incidence of immunodeficiency, including immunoglobulin A deficiency and other antibody defects. Other autoantibodies obtained should be guided by clinical and laboratory manifestations, such as petechiae, anemia, coagulopathy, cerebritis, and thyroid abnormalities.
Patients should be evaluated for traditional risk factors for atherosclerosis, with the patient’s fasting lipid profile, homocysteine level, fasting glucose level, and body mass index obtained. Risks should be stratified and treated. Hepatitis demonstrated by laboratory evaluation is not uncommon.
Obtain pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DLCO), to evaluate baseline pulmonary status and to look for subtle disease not seen on chest radiographs.
Cognitive function testing should be considered in patients with systemic lupus erythematosus (SLE), particularly if changes in behavior or school function are observed. Testing should include academics, executive function, attention, and memory. Recently, a set of tests has been established by consensus criteria as a screening evaluation. [16]
The Pediatric Automated Neuropsychological Assessment Metrics, a computer-based neuropsychological evaluation tool, has been initially validated in children diagnosed with SLE. [17] However, further testing is needed to determine its sensitivity and specificity to change in clinical status.
Staging
Lupus is not generally staged as a disease. However, staging criteria have been proposed to help assess the degree of illness. Determining which set of organs is inflamed is useful to decide treatment options. Currently there is ongoing work to define disease flare and remission criteria both for systemic disease and lupus nephritis in children. [18]
Imaging Studies
Obtain chest radiographs and electrocardiograms. Other imaging studies should be guided by clinical manifestations and may include the following:
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Magnetic resonance imaging (MRI) of the brain - However, many patients with central nervous system (CNS) lupus do not have MRI abnormalities or have nonspecific bright areas that do not correlate with clinical observations of CNS deficits
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Renal ultrasonography
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Nuclear medicine evaluation for renal function
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High-resolution computer tomography (CT) scanning to diagnose and evaluate for pulmonary fibrosis
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Dual-energy radiographic absorptiometry to evaluate bone density
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Angiography (usually MR or CT) to assess for thrombi for lupus-related antiphospholipid syndrome (APS)
Procedures
The most common procedure used in the diagnostic evaluation of systemic lupus erythematosus (SLE) is a tissue biopsy to confirm the diagnosis and to evaluate disease severity. This is particularly useful in evaluating the severity of renal involvement. [19]
Skin biopsy is used for diagnostic purposes when the diagnosis is not clear; lesional and sun-exposed skin may show positive immunofluorescence for complement and immune complexes. However, skin biopsy is rarely necessary to make the diagnosis of SLE. Renal or liver biopsy is obtained more often for evaluation of disease severity and to determine the intensity of the medical regimen required for treatment.
Histologic Findings
Fibrinoid deposits are found in blood vessel walls of affected organs. The parenchyma of these organs may contain hematoxylin bodies representing degenerated cells. Other histologic manifestations are associated with the particular organ. Immunofluorescence often reveals immune complexes and complements. The most important histology related to treatment decision is renal histopathology. The location of immune complexes (ie, subepithelial, subendothelial, intramembranous) is also important in prognosis.
Renal biopsy findings are classified according to the World Health Organization (WHO) classification and correlate with clinical morbidity and mortality. [20] Staging for WHO histologic class and for acuity and chronicity of renal histologic manifestations is important in determining optimal therapy.
Patients may have combinations of the following classifications on biopsy findings, and all types should be reported:
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Class I - Defined by normal findings on light microscopy, immunofluorescence, and electron microscopy
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Class IIA disease - Has minimal mesangial deposits and a good prognosis
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Class IIB disease - Associated with lymphocytic infiltration and a variable prognosis
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Class III disease - Characterized by focal, segmental, proliferative mesangial changes and is associated with chronic renal disease; it is subtyped into (1) active necrotizing lesions, (2) active sclerosing lesions, and (3) sclerosing lesions
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Class IV disease - Defined as diffuse proliferation, with most glomeruli demonstrating cellular proliferation of epithelial, endothelial, and mesangial cells with cellular or fibrous crescent formation; class IV has been further subdivided into segmental disease (IV-S) and global disease (IV-G); class IV is associated with an increased risk of end-stage renal disease; class IV disease involves advanced sclerosing lesions; this stage is subtyped into (1) without segmental lesions, (2) with active necrotizing lesions, (3) with active sclerosing lesions, and (4) sclerosing lesions
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Class V disease - Defined as a membranous process with significant proteinuria, which is often poorly responsive to treatment; this is subdivided into (1) pure membranous lesions, (2) associated with lesions of Class II, (3) associated with lesions of Class III, and (4) associated with lesions of Class IV
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Class VI disease - Advanced sclerosing glomerulonephritis (≥90% global sclerosis without activity)
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The classic malar rash, also known as a butterfly rash, with distribution over the cheeks and nasal bridge. Note that the fixed erythema, sometimes with mild induration as seen here, characteristically spares the nasolabial folds.
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In systemic lupus erythematosus (SLE), many genetic-susceptibility factors, environmental triggers, antigen-antibody responses, B-cell and T-cell interactions, and immune clearance processes interact to generate and perpetuate autoimmunity.
