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Laboratory Investigations in Rheumatology
Dr.Wessam El Gendy MDProf. of Clinical pathology
Systemic Lupus erythematosis Scleroderma Polymyositis/Dermatomyositis Rheumatoid Arthritis
Laboratory test results help diagnose monitor disease course predict disease outcome assess the response to therapy and gain insight into disease etiology or
pathogenesis.
Systemic Lupus ErythematosisSLE
There are many laboratory tests which aid the physician in making a lupus diagnosis.
Routine clinical tests which suggest that the person has an active systemic disease.
Sedimentation rate (ESR) and CRP (C-reactive protein) binding, both of which are frequently elevated in inflammation from any cause
Serum protein electrophoresis which may reveal increased gamma globulin and decreased albumin
Routine blood counts which may reveal anemia and low platelet and white cell counts.
Routine chemistry panels which may reveal– kidney involvement ;serum blood urea nitrogen
and creatinine– abnormalities of liver function tests– increased muscle enzymes (such as CPK) if
muscle involvement is present.
Immunological Tests in SLE
Anti-nuclear antibody test (ANA) to determine if autoantibodies to cell nuclei are present in the blood
Anti-DNA antibody test to determine if there are antibodies to the genetic material in the cell
Anti-Sm antibody test to determine if there are antibodies to Sm, which is a ribonucleoprotein found in the cell nucleus
Serum complement test to examine the total level of a group of proteins which can be consumed in immune reactions.
The Antinuclear Antibody (ANA or FANA) Test
The immunofluorescent antinuclear antibody (ANA or FANA) test is positive in almost all individuals with systemic lupus (97 percent), and is the most sensitive diagnostic test currently available for confirming the diagnosis of systemic lupus when accompanied by typical clinical findings.
Anti-nuclear AbANA
While the ANA is often positive in connective tissue diseases, it is also often positive in other non-autoimmune diseases such as:
1. Infectious disease (e.g. EBV, and viral hepatitis)2. Neoplastic diseases (e.g. leukemia, lymphoma,
melanoma, and other solid tumors), 3. other diseases such as primary biliary cirrhosis.
A significant number of healthy individuals may have a positive ANA.
However, positive ANAs in these non connective tissue diseases usually occur at a lower titre
Following patient progress?
ANA titers do not correlate with disease activity and the practice of ordering this test to monitor the course of SLE should be abandoned.
Expression of ANA Results.
If the patient has an ANA of 1:40 probably there is nothing.
If the ANA is 1:80 you need to investigate the case.
If the ANA is 1:160 or higher, rheumatologist should take a look – not all of them will have something, but some will.
"Does ANA-negative lupus exist "
"ANA-negative" person should be re-evaluated using: anti-Sm, anti-Ro, anti-RNP as well as clinical criteria.
However, systemic lupus erythematosus (SLE) is rarely, if ever, present when an ANA test is negative.
Test is overly sensitive 95%; not diagnostic without clinical features
Other Autoantibodies in Lupus
Antibodies to DNA Antibodies to histones Antibodies to the Sm antigen Antibodies to RNP (ribonucleoprotein) Antibodies to Ro/SS-A Antibodies to Jo-1 are associated with
polymyositis.
Antibodies to PM-Scl are associated with certain cases of polymyositis that also have features of scleroderma.
Antibodies to Scl-70 are found in people with a generalized form of scleroderma.
Antibodies to the centromere
Following patient progress:
Most autoantibodies (RF, ANA , ENA [extractable nuclear antigen], anti-Jo-1, etc) do not vary with disease flare-ups and remissions and need be ordered only once during the diagnostic work-up.
Follow up of SLE
Complete blood count: anemia, thrombocytopenia, neutropenia
ESR & CRP Anti-ds DNA Serum complement Anti-cardiolipin Ab/ lupus anticoagulant in
cases with recurrent abortions or thrombosis
Screening
With few exceptions, broad-based screening tests are generally not recommended in the absence of suggestive history and/or physical findings because false-positive rates may be high.
Methodology
Immunoflurescence ELISA Immunoblot
Rheumatoid Arthritis
There is no single test that can be used to diagnose rheumatoid arthritis; it is a diagnosis that is made through clinical evaluation with the assistance of laboratory and non-laboratory testing.
Lab – Evidence of Inflammation
Acute phase response CRP Erythrocyte sedimentation rate
Laboratory investigations in Rheumatoid Arthritis
Complete blood count CBC Erythrocyte sedimentation rate (ESR) &
C-reactive protein (CRP) Rheumatoid factor (RF)• Anti-cyclic citrullinated peptide (CCP)
“Rheumatoid factor”
“Rheumatoid factor” is a misnomer; it confers a specificity to this test that is not deserved.
Rheumatoid factors are immunoglobulin M antibodies directed against the Fc (constant) region of the immunoglobulin G molecule
Rheumatoid factor in Rheumatoid Arthritis
Negative in 30 percent of patients early in illness
If initially negative, repeat 6 - 12 months after disease onset
Not an accurate measure of disease progression.
Non-Rheumatic Conditions
Aging
HCV Infection: bacterial endocarditis, liver
disease, tuberculosis, syphilis, viral infections (especially mumps, rubella and influenza), parasitic diseases
Pulmonary disease: sarcoidosis, interstitial pulmonary fibrosis, silicosis, asbestosis
Miscellaneous diseases: primary biliary
cirrhosis, malignancy (especially leukemia and
colon cancer)
Conditions Associated with a Positive Rheumatoid Factor Test
Rheumatoid arthritis (50 to 90%) Systemic lupus erythematosus (15 to 35%) Sjögren's syndrome (75 to 95%) Systemic sclerosis (20 to 30%) Cryoglobulinemia (40 to 100%) Mixed connective tissue disease (50 to 60%)
Methodology
Its presence can be detected with a wide variety of techniques (e.g., agglutination of sheep red blood cells, latex particles coated with human immunoglobulin G, enzyme linked immunosorbent assay or nephelometry).
Unfortunately,the measurement is not standardized in many laboratories.
Rheumatoid factor is present in most people at very low levels, but higher levels are present in 5%–10% of the population, and this percentage rises with age.
Anti-CCP
Anti-cyclic citrullinated peptide Specificity = 90% Sensitivity = 50-80%
Anticyclic citrullinated peptideAnti-CCP
Tends to correlate well with disease progression
Increases sensitivity when used in combination with rheumatoid factor
More specific than rheumatoid factor (90 versus 80 percent);
If present in such a patient at a moderate to high level, it not only confirms the diagnosis but also may indicate that the patient is at increased risk for damage to the joints.
Low levels of this antibody are less significant.
Anti-CCP
Can detect approximately 80% of all RA patients, but is rarely positive in non-RA patients, giving it a specificity of around 98%.
In addition, ACP antibodies can be often detected in early stages of the disease, or even before disease onset.
Flow chartRF
Anti-CCP
RF –iveAnti-CCP –iveVery unlikely
RF –iveAnti-CCP +ive
Early RA
RF +iveAnti-CCP +ive
Typical presentation
RF +iveAnti-CCP –ive
RA or infection
Interpretation
The physician must be aware of the sensitivity and specificity of each test. Tests with low sensitivity but high specificity are helpful only if positive, whereas tests with low specificity should not be ordered in the absence of a high diagnostic suspicion
The clinical laboratory shouldclearly state the type of immunologicprocedure performed
Define the reference range when including the cut-off values and indicate what percent of the normal population is included in the reference range.
Lab investigations of Lupus Nephritis
Monitoring with regular urinalysis & serum creatinine Screen all pts with proteinuria for ANA Anti ds DNA
In about 60% with SLE Levels often reflect disease activity Decreases with Rx ( ANA remains positive)
Serum complement
Anti-phospholipid antibodies
Sjogren Syndrome Diagnostic Criteria
Presence of anti-Ro/SS-A (60%), anti-La/SS-b (30%), antinuclear antibodies, or rheumatoid factor.
Polymyositis/Dermatomyositis
Blood testing usually (but not always) reveals abnormally high levels of muscle enzymes, CPK or creatinine phosphokinase, aldolase, SGOT, SGPT, and LDH.
These enzymes are released into the blood by muscle that is being damaged by inflammation. They can also be used as measures of the activity of the inflammation.
Other routine blood and urine tests can also look for internal organ abnormalities.
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