SYSTEMIC LUPUS ERYTHEMATOSUS
- American Rheumatism Association (ARA) '11 criteria' for the diagnosis of SLE - http://webrheum.bham.ac.uk/teaching/clinimmunol/sle_ara.htm
- Systemic Lupus Erythematosus: a comprehensive review - http://www.emedicine.com/med/topic2228.htm
- Systemic Lupus Erythematosus: an emergency medicine perspective - http://www.emedicine.com/emerg/topic564.htm
- Drug-Induced Lupus Erythematosus - http://www.emedicine.com/derm/topic107.htm
- Antiphospholipid Antibody Syndrome and Pregnancy - http://www.emedicine.com/med/topic3258.htm
- Lupus Nephritis Review - http://www.emedicine.com/med/topic1597.htm
- Diffuse Proliferative Glomerulonephritis - http://www.emedicine.com/med/topic882.htm
- Systemic Lupus Erythematosus: neurological manifestations - http://www.emedicine.com/neuro/topic360.htm
- Libman-Sacks Endocarditis Review - http://www.emedicine.com/med/topic1295.htm
- Neonatal Lupus and Cutaneous Lupus Erythematosus in Children - http://www.emedicine.com/ped/topic602.htm
- Subacute Cutaneous Lupus Erythematosus - http://www.emedicine.com/derm/topic248.htm
- Systemic Lupus Erythematosus: rehabilitation of the patients - http://www.emedicine.com/pmr/topic135.htm
- Mixed Connective Tissue Disease - http://www.emedicine.com/derm/topic766.htm
- A list of autoantibodies checked in 'Connective Tissue Disorders' - http://www.labtestsonline.org/understanding/analytes/autoantibodies/sys_ab_table.pdf
- American Association of Clinical Chemistry: Antinuclear Antibody (ANA) Test - http://www.labtestsonline.org/understanding/analytes/ana/glance.html
- Anti-dsDNA (Double-Stranded) Antibodies - http://www.labcorp.com/datasets/labcorp/html/chapter/mono/se018400.htm
- Medline Plus: Anti-smooth muscle antibody - http://www.nlm.nih.gov/medlineplus/ency/article/003531.htm
- Royal College of Pathologists of Australasia: Histone antibodies - serum - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=87
- Sjögren's Antibodies (Anti-SS-A (also called anti-Ro) / Anti-SS-B (also called anti-La)) - http://www.labcorp.com/datasets/labcorp/html/chapter/mono/se025300.htm
- Royal College of Pathologists of Australasia: Immunoglobulins G, A, M - serum - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=90
- Medline Plus: Antimitochondrial antibody - http://www.nlm.nih.gov/medlineplus/ency/article/003529.htm
- Medline Plus: Antithyroglobulin antibody - http://www.nlm.nih.gov/medlineplus/ency/article/003557.htm
- Medline Plus: Antithyroid microsomal antibody - http://www.nlm.nih.gov/medlineplus/ency/article/003556.htm
- Royal College of Pathologists of Australasia: Complement components C3 and C4 - serum - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=62
- Royal College of Pathologists of Australasia: Complement CH50 or CH100 - serum - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=60
- Royal College of Pathologists of Australasia: Rheumatoid factor - serum - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=347
Chemical Pathology Test/s:
- American Association of Clinical Chemistry:
C-Reactive Protein (CRP) - http://www.labtestsonline.org/understanding/analytes/crp/glance.html
- American Association of Clinical Chemistry:
Serum Iron - http://labtestsonline.org/understanding/analytes/serum_iron/glance.html
- American Association of Clinical Chemistry: Total iron-binding capacity - http://labtestsonline.org/understanding/analytes/tibc/glance.html
- American Association of Clinical Chemistry: Serum ferritin level - http://labtestsonline.org/understanding/analytes/ferritin/glance.html
- Medline Plus: Protein - urine - http://www.nlm.nih.gov/medlineplus/ency/article/003580.htm
- American Association of Clinical Chemistry: Protein Electrophoresis and Immunofixation Electrophoresis - http://www.labtestsonline.org/understanding/analytes/electrophoresis/glance.html
- American Association of Clinical Chemistry:
Complete Blood Count - http://labtestsonline.org/understanding/analytes/cbc/glance.html
- American Association of Clinical Chemistry: Erythrocyte sedimentation rate (ESR) - http://www.labtestsonline.org/understanding/analytes/esr/glance.html
- American Association of Clinical Chemistry:
Haemoglobin - http://labtestsonline.org/understanding/analytes/hemoglobin/glance.html
- American Association of Clinical Chemistry: Peripheral blood smear - http://labtestsonline.org/understanding/analytes/blood_smear/glance.html
- American Association of Clinical Chemistry:
Platelet Count - http://labtestsonline.org/understanding/analytes/platelet/glance.html
- American Association of Clinical Chemistry: Reticulocyte Count - http://www.labtestsonline.org/understanding/analytes/reticulocyte/glance.html
- Medline Plus: Coombs’ test - direct - http://www.nlm.nih.gov/medlineplus/ency/article/003344.htm
- Medline Plus: Cryoglobulins - http://www.nlm.nih.gov/medlineplus/ency/article/003555.htm
- Royal College of Pathologists of Australasia: Activated partial thromboplastin time (APTT) - plasma - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=224
- Royal College of Pathologists of Australasia: Prothrombin time (PT) - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=304
- Royal College of Pathologists of Australasia: Lupus band test - skin (testing of nonlesional nonexposed skin) - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=662
- Medline Plus: Skin lesion biopsy - http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm
Routine Radiological Study:
- Medline Plus: Chest X-ray
Additional tests that may be asked to rule out/monitor clinical/subclinical lupus nephritis:
- Royal College of Pathologists of Australasia: Urinalysis - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=794
- Royal College of Pathologists of Australasia: 24 hrs urinary proteins - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=572
- Royal College of Pathologists of Australasia: Urine microscopy and culture - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=172
- Royal College of Pathologists of Australasia: Creatinine - plasma or serum - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=494
- Royal College of Pathologists of Australasia: Creatinine clearance - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=491
- ACR practice guideline for the performance of an Ultrasound examination of the Abdomen or Retroperitoneum - http://www.acr.org/s_acr/bin.asp?TrackID=&SID=1&DID=12175&CID=539&VID=2&DOC=File.PDF
- ACR Practice Guideline for the Performance of Adult and Paediatric Renal Scintigraphy - http://www.acr.org/s_acr/bin.asp?TrackID=&SID=1&DID=12280&CID=1074&VID=2&DOC=File.PDF
- Medline Plus: Renal biopsy - http://www.nlm.nih.gov/medlineplus/ency/article/003907.htm
Additional test that may be asked in a SLE case with recurrent pneumonitis / shrinking lung syndrome:
- ACR Practice Guideline for Performing and Interpreting Diagnostic Computed Tomography (CT) - http://www.acr.org/s_acr/bin.asp?CID=541&DID=12265&DOC=FILE.PDF
ATS/ERS Task Force: Standardisation of lung function testing - Standardisation of spirometry - http://www.ersnet.org/ers/lr/browse/viewPDF.aspx?id_attach=10288
ATS/ERS Task Force: Standardisation of lung function testing - General considerations for lung function testing - http://www.ersnet.org/ers/lr/browse/viewPDF.aspx?id_attach=10205
Additional test that may be asked in a SLE case with Libman-Sacks Endocarditis:
- Echocardiogram: a brief overview - http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm
- Medline Plus: Coronary angiography - http://www.nlm.nih.gov/medlineplus/ency/article/003876.htm
- Medline Plus: Nuclear ventriculography - http://www.nlm.nih.gov/medlineplus/ency/article/003822.htm
- Medline Plus: Aortic angiography - http://www.nlm.nih.gov/medlineplus/ency/article/003814.htm
- Medline Plus: Swan-Ganz - right heart catheterization - http://www.nlm.nih.gov/medlineplus/ency/article/003870.htm
Additional tests that may be asked in patients with SLE and myositis, cutaneous vasculitis and patients with overlap syndromes:
- Royal College of Pathologists of Australasia: Creatine kinase (CK) - plasma or serum - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=492
- Medline Plus: Electromyography - http://www.nlm.nih.gov/medlineplus/ency/article/003929.htm
- Medline Plus: Muscle biopsy - http://www.nlm.nih.gov/medlineplus/ency/article/003924.htm
- Medline Plus: Nerve biopsy - http://www.nlm.nih.gov/medlineplus/ency/article/003928.htm
Additional tests that may be asked in a suspected case of cerebral lupus or new onset generalized seizures:
Royal College of Pathologists of Australasia: Electrolytes - plasma or serum - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=500
Royal College of Pathologists of Australasia: Glucose - plasma, serum, or whole blood - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=531
Royal College of Pathologists of Australasia: Calcium - plasma or serum - http://www.rcpamanual.edu.au/sections/pathologytest.asp?s=33&i=424
American Association of Clinical Chemistry: Arterial Blood Gases (ABG's) - http://labtestsonline.org/understanding/analytes/blood_gases/test.html
Lumbar Puncture - http://www.mtio.com/lupus/prolp.htm
ACR Practice Guideline for the Performance and Interpretation of Magnetic Resonance Imaging (MRI) of the Brain - http://www.acr.org/s_acr/bin.asp?TrackID=&SID=1&DID=12250&CID=542&VID=2&DOC=File.PDF
ACR Practice Guideline for the Performance of Paediatric and Adult Body Magnetic Resonance Angiography (MRA) - http://www.acr.org/s_acr/bin.asp?TrackID=&SID=1&DID=22485&CID=546&VID=2&DOC=File.PDF
ACR Practice Guideline for the Performance of Magnetic Resonance Imaging (MRI) of the Adult Spine - http://www.acr.org/s_acr/bin.asp?TrackID=&SID=1&DID=12249&CID=542&VID=2&DOC=File.PDF
Electroencephalography (EEG) - http://www.emedicinehealth.com/electroencephalography_eeg/article_em.htm
Additional tests that may be asked in drug-induced lupus erythematosus (DILE):
- Anti-DNA (Single-Stranded) Antibodies- http://www.labcorp.com/datasets/labcorp/html/chapter/mono/bs001000.htm
- Antihistone antibodies - http://www.labcorp.com/datasets/labcorp/html/chapter/mono/se016000.htm
- American Association of Clinical Chemistry: Blood Urea Nitrogen (BUN) - http://labtestsonline.org/understanding/analytes/bun/test.html
- American Association of Clinical Chemistry: Liver Function Tests (LFT's) - http://labtestsonline.org/understanding/analytes/liver_panel/glance.html
Additional tests that may be asked in a suspected case of antiphospholipid syndrome (APS), especially in a pregnant lady:
- American Association of Clinical Chemistry:
Antiphospholipid Antibodies - http://www.labtestsonline.org/understanding/analytes/antiphospholipids/glance.html
- American Association of Clinical Chemistry: Anticardiolipin Antibodies - http://www.labtestsonline.org/understanding/analytes/cardiolipin/glance.html
Additional test that may be asked in postmenopausal women and patients on long-term corticosteroids:
International Society for Clinical Densitometry (ISCD): Official Positions 2005 Updated - http://www.iscd.org/Visitors/pdfs/ISCD_OP2005_000.pdf
Precision Assessment and Radiation Safety for Dual energy X-ray Absorptiometry (DXA): White Paper of the International Society for Clinical Densitometry - http://www.iscd.org/Visitors/pdfs/RadiationSafetyWhitePaperWebPosting2005-06.pdf
Tests which yield 'false positive' results in SLE patients:
- Medline Plus: Mononucleosis spot test - http://www.nlm.nih.gov/medlineplus/ency/article/003454.htm
- American Association of Clinical Chemistry: VDRL - http://www.labtestsonline.org/understanding/analytes/syphilis/glance.html
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.
- 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.
- The incidence of anti-ssDNA antibodies is characteristically high is drug-induced lupus erythematosus (DILE).
- 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).
- 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.
- 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:
- Unexplained 2nd or 3rd trimester fetal death or stillbirth.
- Past history of three or more spontaneous abortions.
- Severe preeclampsia at less than 34 weeks of gestation
- Severe fetal growth restriction.
- 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 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.
- 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!).
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.
- 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.
- 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.
- 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:|
|3||Focal segmental nephritis|
|4||Diffuse proliferative 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 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.