SYSTEMIC LUPUS ERYTHEMATOSUS

Measures:

Lab Studies:

Immunological Tests:

Chemical Pathology Test/s:

Haematology Tests:

Histological Test/s:

Routine Radiological Study:

  • Medline Plus: Chest X-ray

Additional tests that may be asked to rule out/monitor clinical/subclinical lupus nephritis:

Additional test that may be asked in a SLE case with recurrent pneumonitis / shrinking lung syndrome:

Additional test that may be asked in a SLE case with Libman-Sacks Endocarditis:

Additional tests that may be asked in patients with SLE and myositis, cutaneous vasculitis and patients with overlap syndromes:

Additional tests that may be asked in a suspected case of cerebral lupus or new onset generalized seizures:

Additional tests that may be asked in drug-induced lupus erythematosus (DILE):

Additional tests that may be asked in a suspected case of antiphospholipid syndrome (APS), especially in a pregnant lady:

Additional test that may be asked in postmenopausal women and patients on long-term corticosteroids:

Tests which yield 'false positive' results in SLE patients:

Interpretation of Measures:

In a SLE patient, what to expect from the test for:

Antinuclear Antibody (ANA):

  • It is an antibody to nucleosomal DNA-histone complexes. ANA is the most commonly found autoantibody in SLE  patient; found in almost 95% of the patients. It's absence, however, does not rule out SLE. If you are searching for one screening test for SLE, this is the most appropriate test. Virtually all patients with SLE have an ANA titre of 1:80 or higher.
    •

Anti-dsDNA Antibodies:

  • It is found in about 70% cases and is a more specific antibody for SLE than ANA (which is very sensitive but not very specific!). Since, finding ANA is not 'diagnostic' of SLE, all patients with positive ANA should be subjected to anti-dsDNA antibody testing, which is indeed the most specific test for SLE. Another good thing about this autoantibody is that its levels correlate well with disease severity, in particular lupus nephritis.
    •

Anti-ssDNA Antibodies:

  • The incidence of anti-ssDNA antibodies is characteristically high is drug-induced lupus erythematosus (DILE).

Anti-histone Antibodies:

  • Histones are proteins typically found in cell nuclei. These are characteristically found in drug-induced lupus erythematosus (DILE). Specifically speaking, the antihistone antibody that is often implicated in DILE is immunoglobulin G (anti-[H2A-H2B] DNA).

Anti-Sm Antibodies:

  • It is found in about 30-40% blacks and Asians cases and 10-20% whites. Unlike, anti-dsDNA antibodies whose levels change with changing disease severity, the levels of anti-Sm antibody by and large remain the same throughout the course of the disease. Since, it is found in not found in more than half of the patients and doesn't correlate with disease severity, searching for this antibody is not of high value in a research setting.

Anti-SSA/Ro and SSB/La Antibodies:

  • Although these antibodies are found in only 15-20% of SLE patients, a researcher would still be interested in them because of their correlation with certain specific manifestations of SLE, primarily the 'cutaneous' ones: malar (butterfly) rash, discoid rash and photosensitivity. They are also of interest because they are found in high percentage in 'neonatal lupus erythematosus' cases. Any neonate presenting with a skin rash and congenital heart block should be subjected to this test. It is pertinent to mention here that almost 50% of the neonates with lupus erythematosus have mothers with no apparent disease.

Antibodies to ribosomal P protein:

  • This antibody would be of interest to a researcher doing research in 'lupus cerebritis'. It is highly unlikely that an SLE patient not having lupus cerebritis would come out to be positive for this antibody.

Antiphospholipid Antibodies:

  • These antibodies are found in almost 30-40% SLE cases. Their presence confirms the diagnosis of 'antiphospholipid syndrome' (APS), which can occur both independently and in association with SLE. The hallmark of this syndrome is the propensity to develop arterial and venous thrombi e.g. a lady coming with recurrent miscarriages could well be suffering from antiphospholipid syndrome. There are many types of these antibodies and can be detected with different lab tests e.g. anticardiolipin (aCL), lupus anticoagulant (LAC; detected by PL-dependent clotting assays, without correction with normal plasma) and antibodies to a cofactor that binds to phospholipids—beta-2 glycoprotein I. The exact diagnostic criteria for APS is finding LAC IgG or IgM aCL in medium-to-high levels, or both, on two occasions at least several weeks apart. Isolated IgA anticardiolipin (aCL) antibodies are not diagnostic of APS and their precise clinical relevance is yet undetermined. Importantly, aCL and LAC correlate well with disease severity. These antibodies can cause false positive VDRL test. Every SLE patient with positive VDRL tests must therefore be subjected to antiphospholipid antibodies testing to rule out antiphospholipid syndrome. In a pregnant lady, antiphospholipid antibodies should be checked regardless of the presence or absence of clinical manifestations suggestive of SLE provided one of the following obstetrical indications is found:
    •
  1. Unexplained 2nd or 3rd trimester fetal death or stillbirth.
  2. Past history of three or more spontaneous abortions.
  3. Severe preeclampsia at less than 34 weeks of gestation
  4. Severe fetal growth restriction.
    5.

Quantitative immunoglobulins:

  • Expect hypergammaglobulinemia and a higher incidence of immunodeficiency in SLE patients.

Activated partial thromboplastin time (aPTT):

  • Expect the aPTT to be raised in SLE patients, especially in cases of antiphospholipid syndrome. It remains unchanged despite of the addition of 'normal plasma' in patients plasma.

Rheumatoid Factor (RF):

  • It is found in 20-40% cases of SLE. It is a non-specific finding.

Coombs Antibody:

  • Coombs positive haemolytic anaemia is a known feature of SLE.

ESR & CRP:

  • These are acute phase reactants. ESR level is usually found raised in SLE patients. CRP level usually remains unchanged in SLE except when secondary infection, serositis (pleuritis, pericarditis), nephritis or arthritis develop. The levels of acute phase reactants do not correlate well with disease severity.

Complete Blood Count (CBC):

  • Expect anaemia, leucopoenia and thrombocytopenia in a SLE patient. Anaemia could be 'anaemia of chronic disease' (60-80% cases; findings = hypochromic/normochromic normocytic peripheral blood picture; ↓ iron level; ↓ TIBC and ↑ ferritin level) &/or haemolytic anaemia ((10% cases; findings = ↑ reticulocyte count). An exception is drug-induced lupus erythematosus (DILE) patients in which anaemia is usually absent. White cell count is generally in the range of 2500-400; it is rare to be <1500. Platelet count generally falls in active disease (30-50% of cases) and spontaneously ameliorates with the remission of the active phase. An exception is a subset of patients who suffer from antiphospholipid syndrome who develop severe thrombocytopenia which doesn't ameliorate spontaneously and requires specific therapy in the form of intravenous immunoglobulins therapy and may be splenectomy.

Renal Function Tests:

  • These tests should be asked serially because a patient with no clinical manifestation of lupus nephritis may come out to be having abnormal renal function tests. Suggestive lab findings include: visualization of >05 RBC's/HPF; >05WBC/HPF with negative cultures; casts (RBC, granular, tubular, mixed or heme casts) on urinalysis; raised creatinine levels; >0.5gm proteins in 24hrs.

Liver Function Tests:

  • LFT's are only mildly or not at all deranged by SLE per se. If found markedly deranged, most probably, it is a side effect of NSAID therapy.

Serum Creatinine Kinase:

  • Raised levels indicate myositis, which could be secondary to SLE, MCTD (mixed connective tissue disease = SLE +  Polymyositis + Systemic Sclerosis) or drug-related (steroid, hydroxychloroquine) myopathy. It is not a very sensitive test because normal levels are sometimes found in clinical or biopsy-proven disease. The only reliable differentiation between inflammatory and medication-induced myopathy can be made by muscle biopsy. 

Complement levels C3, C4, CH50:

  • In active SLE, complement factors are consumed in the ongoing inflammatory process with the obvious result that their levels would be found subnormal in most of the active SLE patients. Low complement levels (in particular low C3 levels) could, therefore, be used as a marker of ongoing active disease process. In some patient of SLE, however, there is present a 'congenital' deficiency of complement factors, especially C2, C4 & CH50. In such patient, obviously, complement levels cannot be used as markers of active disease. One can suspect congenital deficiency when one finds low complement levels in a patient with only a mild disease. In cases of drug-induced lupus erythematosus (DILE), the levels of complement levels usually and characteristically remain unchanged. This is a major difference between DILE and SLE (besides the higher incidence of anti-histone and anti-ssDNA antibodies). A pregnant lady with SLE and 'raised' complement levels should be suspected for 'pre-eclampsia' and followed accordingly.

Electrolytes, Glucose, Calcium & ABG's:

  • These are especially indicated in cases of new onset generalized seizures.
    •

Plain radiographs of the joints:

  • SLE produces migratory, asymmetrical, non-erosive arthritis. In rheumatoid arthritis, there occurs symmetrical erosive arthropathy. In seronegative spondyloarthritides (like ankylosing spondylitis), there occurs asymmetrical erosive arthritis. Absence of erosions being a pertinent negative finding, the pertinent positive findings include periarticular or diffuse osteoporosis and soft tissue swelling.

Chest X-Ray:

  • Basically done to rule out / monitor pleuritis, pleural effusion, pneumonitis and cardiomyopathy.

Brain MRI/magnetic resonance angiography (MRA):

  • Any SLE patient developing stroke can be subjected to this test. This expensive radiological investigation, although preferred over CT scan, can only confirm the presence of cerebrovascular accident (CVA); it cannot apprise anything about the possible aetiology of CVA (MRI can't tell that cerebral vasculitis is secondary to SLE!).
    •

Electroencephalography (EEG):

  • It is usually indicated in a patient with recurrent seizures. Also in patients in whom the anticonvulsant therapy is withdrawn, EEG can be done in order to determine the recurrence risk. A normal EEG, however, doesn't rule out the possibility of recurrence of seizures.

Lumbar Puncture:

  • Any SLE patient with neurological signs can be subjected to this test. The aim would be to rule the infective causes (not SLE). SLE causes 'non-specific' rise in the cell count and protein level (in 50% of patients) and also fall in glucose level in CSF.

Echocardiogram :

  • It is basically done to rule out / monitor Libman Sacks endocarditis, any effusion causing pericardial pain and also to assess for pulmonary hypertension.

EMG and nerve conduction studies (NCS):

  • These tests are asked in patients who develop some peripheral complication of SLE. The EMG findings of lupus myositis and dermatomyositis and polymyositis are exactly the same. Moreover, a normal EMG study doesn't rule out the possibility of myositis. 

Dual energy x-ray absorptiometry (DEXA):

  • It is primarily indicated in postmenopausal women and patients on long-term corticosteroids and the aim is to rule out osteoporosis.

Pulmonary Function Tests:

  • Basically required to evaluate baseline pulmonary disease. Diffusing capacity of the lung for carbon monoxide (DLCO) should also be checked besides pulmonary function tests.

Renal Biopsy:

  • Based on WHO classification, there are 05 types of lupus nephritis depending upon light microscopy, electron microscopy, and immunofluorescence findings.
WHO Classification of SLE Nephritis:
Type Histological Appearance
1 Normal
2a Mesangial deposits
2b Mesangial hypercellularity
3 Focal segmental nephritis
4 Diffuse proliferative nephritis
5 Membranous nephritis

Since sampling errors is not a rarity during renal biopsy, the results of the biopsy should always be correlated with the clinical and laboratory findings. Different studies have suggested that the biopsy specimens should be sent to those pathologists who are working in larger medical centres with substantial SLE patient populations. Renal biopsy has predictive prognostic value - advanced is the type of lupus nephritis, worse is the prognosis and thus aggressive should be the treatment regimen.

Skin Biopsy:

  • Skin biopsy is rarely needed to make the diagnosis of SLE. Some SLE patient , however, present quite atypically. Biopsy of the skin lesions can unexpectedly yield the diagnosis of SLE in such cases.


 

Document Provenance and History

Document Author: Dr. Fazal Danish

Document Created: 4th July 2006

Document Edits:

 

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