eMedicine Specialties > Rheumatology > Systemic Rheumatic Disease
Systemic Lupus Erythematosus: Differential Diagnoses & Workup
Updated: Jan 22, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Drug-induced lupus erythematosus
Vasculitis
Leukemia
Neoplasia
HIV infection
Multiple sclerosis
Parvovirus or other viral infections
Workup
Laboratory Studies
Systemic lupus erythematosus (SLE) is a diagnosis that must be based on the proper constellation of clinical findings and laboratory evidence. Familiarity with the diagnostic criteria helps clinicians to recognize SLE and to subclassify this complex disease based on the pattern of target-organ manifestations.
The 1982 American College of Rheumatology (ACR) criteria summarize features necessary to diagnose SLE.20,21 They are summarized below with a useful mnemonic. The presence of 4 of the 11 criteria yields a sensitivity of 85% and a specificity of 95% for SLE. Keep in mind that individual features are variably sensitive and specific. Patients with SLE may present with any combination of clinical features and serologic evidence of lupus. The following is the ACR diagnostic criteria in SLE, presented in the "SOAP BRAIN MD" acronym:
- Serositis - Pleurisy, pericarditis on examination or diagnostic ECG or imaging
- Oral ulcers - Oral or nasopharyngeal, usually painless; palate is most specific
- Arthritis - Nonerosive, two or more peripheral joints with tenderness or swelling
- Photosensitivity - Unusual skin reaction to light exposure
- Blood disorders - Leukopenia (<4000 cells 103/µL on more than one occasion), lymphopenia (<1500 cells/µL on more than one occasion), thrombocytopenia (<100 X103/µL in the absence of offending medications), hemolytic anemia
- Renal involvement - Proteinuria (>0.5 g/d or 3+ positive on dipstick testing) or cellular casts
- ANAs - Higher titers generally more specific (>1:160); must be in the absence of medications associated with drug-induced lupus
- Immunologic phenomena - dsDNA; anti-Smith (Sm) antibodies; antiphospholipid antibodies (anticardiolipin immunoglobulin G [IgG] or immunoglobulin M [IgM] or lupus anticoagulant); biologic false-positive serologic test results for syphilis, lupus erythematosus (LE) cells (omitted in 1997)
- Neurologic disorder - Seizures or psychosis in the absence of other causes
- Malar rash - Fixed erythema over the cheeks and nasal bridge, flat or raised
- Discoid rash - Erythematous raised-rimmed lesions with keratotic scaling and follicular plugging, often scarring
In patients with high clinical suspicion or high ANA titers, additional testing is indicated. This commonly includes evaluation of antibodies to dsDNA, complement, and ANA subtypes such as Sm, SSA, SSB, and ribonucleoprotein (RNP) (often called the ENA panel). Screening laboratory studies to diagnose possible SLE should include a CBC count with differential, serum creatinine, urinalysis with microscopy, ANA, and, perhaps, basic inflammatory markers. The following are autoantibody tests used in the diagnosis of SLE:22
- ANA - Screening test; sensitivity 95%; not diagnostic without clinical features
- Anti-dsDNA - High specificity; sensitivity only 70%; level variable based on disease activity
- Anti-Sm - Most specific antibody for SLE; only 30-40% sensitivity
- Anti-SSA (Ro) or Anti-SSB (La) - Present in 15% of patients with SLE and other connective-tissue diseases such as Sjögren syndrome; associated with neonatal lupus
- Anti-ribosomal P - Uncommon antibodies that may correlate with lupus cerebritis
- Anti-RNP - Included with anti-Sm, SSA, and SSB in the ENA profile; may indicate mixed connective-tissue disease with overlap SLE, scleroderma, and myositis
- Anticardiolipin - IgG/IgM variants measured with enzyme-linked immunoassay (ELISA) among the antiphospholipid antibodies used to screen for antiphospholipid antibody syndrome
- Lupus anticoagulant - Multiple tests (eg, Direct Russell Viper Venom test) to screen for inhibitors in the clotting cascade in antiphospholipid antibody syndrome
- Coombs test - Coombs test–positive anemia to denote antibodies on RBCs
- Anti-histone - Drug-induced lupus ANA antibodies often this type (eg, with procainamide or hydralazine; perinuclear antineutrophil cytoplasmic antibody [p-ANCA]–positive in minocycline-induced drug-induced lupus)
Other laboratory tests used in the diagnosis of SLE include the following:
- Inflammatory markers: Levels of inflammatory markers, including the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), may be elevated in any inflammatory condition, including SLE. CRP levels change more acutely, and the ESR lags behind disease changes.
- Complement levels: C3 and C4 levels are often depressed in patients with active SLE because of consumption by immune complex–induced inflammation. In addition, some patients have congenital complement deficiency that predisposes them to SLE.
- A CBC count may help to screen for leukopenia, lymphopenia, anemia, and thrombocytopenia, and urinalysis and creatinine studies may be useful to screen for kidney disease.
- Liver test results may be mildly elevated in acute SLE or in response to therapies such as azathioprine or nonsteroidal anti-inflammatory drugs (NSAIDS).
- Creatinine kinase levels may be elevated in myositis or overlap syndromes.
Imaging Studies
- Joint radiography often provides little evidence of SLE given the absence of erosions, even in the presence of Jaccoud arthropathy with deformity or subluxations. The most common radiographic changes in SLE include periarticular osteopenia and soft-tissue swelling.
- Chest radiography and chest CT scanning can be used to monitor interstitial lung disease and to assess for pneumonitis, pulmonary emboli, and alveolar hemorrhage.
- Brain MRI/magnetic resonance angiography (MRA) is used to evaluate CNS lupus for white-matter changes, vasculitis, or stroke, although findings are often nonspecific.
- Echocardiography is used to assess for pericardial effusion, pulmonary hypertension, or verrucous Libman-Sacks endocarditis.
Procedures
- Lumbar puncture may be performed to exclude infection with fever or neurologic symptoms. Nonspecific elevations in cell count and protein level and decrease in glucose level may be found in the cerebrospinal fluid of patients with CNS lupus.
- Renal biopsy is used to identify the specific type of glomerulonephritis, to aid in prognosis, and to guide treatment. Another benefit of renal biopsy is in distinguishing renal lupus from renal thrombosis, which may complicate antiphospholipid antibody syndrome and require anticoagulation rather than immunomodulatory therapy.
- Skin biopsy can help to diagnose SLE or unusual rashes in patients with SLE. Many different rashes may herald SLE, making review by a dermatopathologist important.
Histologic Findings
Renal biopsy is used to confirm the presence of lupus nephritis, to aid in classification of SLE nephritis, and to guide therapeutic decisions. The World Health Organization classification for lupus nephritis is based on light microscopy, electron microscopy, and immunofluorescence findings.
International Society of Nephrology 2003 Revised Classification of SLE Nephritis23
Open table in new window
Table
| Class | Classification | Features |
Class I | Minimal mesangial | Normal light microscopy findings; abnormal electron microscopy findings |
Class II | Mesangial proliferative | Hypercellular on light microscopy |
Class III | Focal proliferative | <50% of glomeruli involved |
Class IV | Diffuse proliferative | >50% of glomeruli involved; classified segmental or global; treated aggressively |
Class V | Membranous | Predominantly nephrotic disease |
Class VI | Advanced sclerosing | Chronic lesions and sclerosis |
| Class | Classification | Features |
Class I | Minimal mesangial | Normal light microscopy findings; abnormal electron microscopy findings |
Class II | Mesangial proliferative | Hypercellular on light microscopy |
Class III | Focal proliferative | <50% of glomeruli involved |
Class IV | Diffuse proliferative | >50% of glomeruli involved; classified segmental or global; treated aggressively |
Class V | Membranous | Predominantly nephrotic disease |
Class VI | Advanced sclerosing | Chronic lesions and sclerosis |
Lupus skin rash often demonstrates inflammatory infiltrates at the dermoepidermal junction and vacuolar change in the basal columnar cells. Discoid lesions demonstrate more-significant skin inflammation, with hyperkeratosis, follicular plugging, edema, and mononuclear cell infiltration at the dermoepidermal junction. In many SLE rashes, immunofluorescent stains demonstrate immunoglobulin and complement deposits at the dermoepidermal basement membrane.
More on Systemic Lupus Erythematosus |
| Overview: Systemic Lupus Erythematosus |
 Differential Diagnoses & Workup: Systemic Lupus Erythematosus |
| Treatment & Medication: Systemic Lupus Erythematosus |
| Follow-up: Systemic Lupus Erythematosus |
| Multimedia: Systemic Lupus Erythematosus |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
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Further Reading
Additional resources on system lupus erythematosus (SLE) are available at Medscape's Lupus Resource Center.
Keywords
systemic lupus erythematosus, SLE, lupus, systemic lupus, multisystem inflammatory disease, autoimmune disorder, chronic autoimmune disease, multisystem microvascular inflammation, nephritis, severe systemic vasculitis, malar rash, discoid rash, photosensitivity, Jaccoud arthropathy, butterfly rash, discoid lupus, lupus profundus, vasculitic purpura, microangiopathic lupus cerebritis, renal lupus, CNS lupus, lupus pneumonitis, chronic lupus interstitial lung disease, lupus disease, lupus peritonitis, drug-induced lupus erythematosus, neonatal lupus, lupus nephritis, lupus skin rash, lupus arthritis, lupus flare
