Laboratory Tests
|
Test |
Description |
Normal |
Abnormal |
Diseases Association(s) |
Comments |
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Anti-CCP Antibodies (Anti-Cyclic
Citrullinated Peptide Antibodies) |
A test done to look for
an abnormality in proteins where there has been a conversion of the amino
acid arginine to citrulline. This test is done by what is called Enzyme-Linked
Immunosbsorbent Assay (ELISA) with a sample of the patient’s blood. |
Less than 20 units |
21-39
units is weak positive |
The test is as sensitive
as standard rheumatoid factor testing but more specific for rheumatoid
arthritis (RA). Anti-CCP antibodies may predict those patients with “undifferentiated
arthritis” who will likely go on to develop rheumatoid arthritis |
This test will be utilized
early on in patients with arthritic symptoms since it is highly correlated
with a diagnosis of rheumatoid arthritis. A positive result should spur
the treating physician to possibly start more aggressive type therapy
early on in the course of the illness to avoid the potential for erosive
arthritis. Erosions may lead to deformity and then subsequent disability
and every therapeutic effort needs to be made to avoid this outcome. |
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Antinuclear antibodies
(ANA) |
One version of this test
is done with the patient's serum put onto a slide which has a human epithelial
cell fixed on its surface. Using
a fluorescent technique where antibodies can be seen under a special microscope,
the reader can interpret whether the result is positive or negative at
different dilutions and also determine the pattern present when the results
are positive |
Negative |
³ 1:80 titer (positive titer).
Major patterns: 1) Homogeneous (or diffuse) nonspecific pattern.
Seen in SLE, RA, drug induced lupus. 2) Speckled seen in SLE, Sjogren's syndrome,
scleroderma, mixed connective tissue disease. 3) Peripheral (or rim)
associated with double stranded DNA antibodies found in the periphery
of the nucleus, primarily seen in SLE. 4) Nucleolar mostly seen in association
with scleroderma |
A positive ANA is seen
in up to 99% of untreated and symptomatic patients with SLE at the time
of diagnosis. Patients with other
diseases such as scleroderma, dermatomyositis/-polymyositis, Sjogren's
syndrome and rheumatoid arthritis may
also have a positive ANA. Liver
disease and thyroid autoimmune disease may lead to a positive test. Medications such as Isoniazid, Hydralazine,
Dilantin, and Procainamide may induce a positive homogenous pattern which
may resolve over time if the medication is discontinued |
Many patients who have
a positive ANA are incorrectly told that they have SLE, but a positive
ANA is not equivalent to this diagnosis.
The patient still needs to meet other criteria for this illness. We are often sent patients to evaluate them
for a positive ANA result and yet many patients have no significant disease
at all (especially with low titer abnormal results). In those situations, reassurance to the patient
about this test is critical. Even
aging itself may lead to a low titer abnormal result. When checked months later, this test may
have then reverted to normal |
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Anti-DNA antibodies |
This test can be performed
in different ways including a technique involving E. coli DNA or using
the tail of an organism called crithidia which has DNA present. The lab test is measuring the presence of
antibodies in the patient's serum to double stranded (or native) DNA |
Negative |
Positive with different
labs having different titers or ranges of abnormal |
The presence of double
stranded DNA antibodies in high titers is associated with SLE. Very high titers are often associated with
kidney or central nervous system involvement as well as active symptoms |
The measurement of these
anti-DNA antibodies at different intervals is an important part of monitoring
the status of a patient with SLE. Sometimes
an increase in the titer may even precede an upcoming flare.
With treatment, often the high titers may shift into a negative
range which would be a good indicator of diminished disease activity |
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Serum complement levels
(C3, C4) |
Complement proteins are
an important part of the body's immune system. Individuals who are born without specific complement components
may even develop diseases such as SLE.
Since these complement proteins are consumed in the process of
inflammation, there levels may be decreased in active disease such as
in lupus vasculitis (SLE). These
are commonly measured by what is called an immunodiffusion technique in
a Petri dish with a patient's serum sample interacting with material put
in special wells in the agar of the dish |
Defined by each lab but
falling within a certain zone and calculated in mg per 100 cc |
A result falling above
or below the established range |
A decreased C3 and C4 level
are often associated with active disease in SLE patients |
The specific components
such as C3 and C4 are measured at intervals when following a patient with
SLE. Low C3 tends to be a much
more reliable indicator of active disease than C4. Rather than looking at these separate complement components, your
physician may also order a total hemolytic complement (CH50)
which evaluates all of the components C1 thru C9 |
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Erythrocyte Sedimenta-tion
Rate (ESR) |
Blood is collected in a
special tube so that it does not clot and then it is transferred to a
calibrated column. The red blood
cells are then allowed to settle towards the bottom of the column over
a one hour period. At the end
of that time, a clear zone is left above the compacted red cells. By measuring this clear zone, one derives a rate of sedimenting
of the cells, i.e. an erythrocyte sedimentation rate or sed rate for short.
The rate of settling is dependent on the presence of inflammatory
and other proteins in the serum |
0-20 mm per hour (in the
elderly the normal range may be increased upwards to 30 mm per hour) |
A result that exceeds the
normal range, any sed rate that is over 100 mm/hr is considered very abnormal
and almost always associated with some significant illness |
Active forms of inflammatory
arthritis are generally associated with an elevated sedimentation rate.
Connective tissue diseases such as SLE, scleroderma and dermatomyositis/-polymyositis
may have an elevated result at times of disease activity but not when
things are quiescent. Polymyalgia
rheumatica is almost always associated with an elevated ESR often exceeding
80-100 mm/hr. (There are rare
exceptions to this rule which have been reported in the medical literature) |
This test is one of two
tests done to assess or measure inflammation in the body. The other inflammation test is called C-reactive
protein (CRP). The sedimentation
rate (ESR) serves as an excellent way to screen for any inflammatory or
hidden (occult) process in the body. In osteoarthritis (which is not a type of
inflammatory joint disease but rather a disease principally of cartilage)
the sed rate is generally normal. In
active rheumatoid arthritis, the sed rate is elevated moderately or significantly
depending on the extent of joint or systemic (organ) involvement.
The interpretation of the sed rate must always be correlated with
clinical findings |
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Rheumatoid Factor |
Rheumatoid factor is an
antibody (IgM) formed towards an IgG antibody and is seen most commonly
in association with rheumatoid arthritis.
The traditional technique involved looking under a microscope for
clumping of latex particles that had been coated with human IgG. This IgM anti-IgG antibody can also be measured
by a machine called a nephelometer to give a quantitative result.
Another technique involves using sheep cells that have been coated
with rabbit IgG (sheep cell agglutination titer) |
RA latex <1:80.
Sheep
cell agglutina-tion titer (SCAT) <1:10.
Rheumatoid factor by nephelome-try - (normal depends on ranges in that
particular lab) |
RA latex ³1:80.
SCAT
³1:10 elevated
above normal range for that lab |
A positive rheumatoid factor
is seen most commonly in rheumatoid arthritis and in high amounts is associated
with more aggressive disease with more erosions of bone at the joints.
Positive rheumatoid factors may be seen in other chronic conditions
including liver disease or lung disease, or chronic infections e.g. subacute
bacterial endocarditis (infection on the heart's valves) |
A low level or titer may
also be seen in the elderly without having any significant disease present
with it but simply related to aging |
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Serum uric acid level |
This is usually included
as part of a general chemistry panel or may be ordered separately and
determined from a patient's serum |
Depending on the specific
lab, usually less than 8.0 mg per 100 cc |
A result which exceeds
the normal range for that lab |
An elevated uric acid level
is associated with gout. In this
form of arthritis, uric acid crystals get into the joint space and incite
a very potent inflammatory reaction.
Occasionally a patient's uric acid may have dropped into the upper
range of normal if they have waited several days after the onset of their
attack before going to the doctor (especially if the attack was related
to an excess alcohol intake or binge) |
Elevated uric acid levels
are most commonly the result of inadequate excretion of uric acid by the
kidney. In children there is an
inherited condition called Lesch - Nyhan syndrome where there is an overproduction
of uric acid resulting in a very high uric acid level in the blood.
In adults, in addition to excess alcohol intake, diuretic treatment
for other problems such as hypertension may also contribute to an elevated
uric acid level |
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C-reactive protein |
This is a test used to
measure inflammation in the body. It
may be done with various techniques in different laboratories including
on a nephelometer or by immunodiffusion radioimmunoassays |
Less than .2-.4 mg% with
minor problems raising this up to 1 mg% |
Moderate elevations of
1-10 mg% may be seen in rheumatic illnesses such as rheumatoid arthritis
and SLE. More marked elevations
above 10 mg% may be seen in severe cases of vasculitis or severe life-
threatening infections |
Elevated CRP levels are
seen in active rheumatoid arthritis.
Increased levels may vary in SLE with a question of whether higher
levels may be seen with superimposed infection in lupus. Vasculitis may also significantly raise the
CRP level |
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| Anti-Scl-70 or Antitopoiso-merase
I |
This test is an immunodiffusion
test which shows this auto-antibody in up to 70% of patients with scleroderma.
This turns out to be an antibody to an enzyme called DNA topoisomerase
which is an important enzyme involved in the replication and transcribing
of DNA in the nucleus |
Negative | Positive |
Diffuse systemic sclerosis
20-30% (scleroderma). Limited systemic sclerosis 10-15% |
This antibody is fairly specific for scleroderma. | |||||
| Anticentromere antibodies | This is a fluorescent staining
test done on serum using human epithelial cells. In a dividing human epithelial cell, fluorescent
staining occurs where the chromosomes have lined up as part of cell division
with the serum reacting to the centromere proteins |
Negative |
Positive staining in the
anticentromere pattern |
Very specific for CREST
syndrome. It sometimes is seen in
a lower percentage of patients with Raynaud's phenomenon (50-90%). Also seen in diffuse systemic sclerosis (5%) |
This may be useful early
in the work-up of a patient for possible scleroderma. |
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| Anti-Ribonucleo-protein
antibody (anti-RNP antibody) |
Antibodies to this cellular
protein produce a speckled pattern on immunofluorescent ANA |
Negative | Positive | High titer of anti-U1 RNP
antibodies occurs in association with mixed connective tissue disease with
features of SLE, scleroderma and polymyositis |
High titers (levels) of
this antibody is very suggestive of mixed connective tissue disease. |
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| Anti-Sm antibody | Antibody to a Sm antigen designated snRNP or small nuclear ribonucleoprotein | Negative |
Positive |
This is seen in approximately
one third of SLE patients and is fairly specific for lupus |
The levels of this antibody
generally do not fluctuate with disease activity. |
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Anti-SS-A (anti-Ro) |
Antibodies are directed to cytoplasmic proteins in a complex with various small RNA antibodies | Negative | Positive |
This is seen in Sjogren's
syndrome. It also has an association
with causing complete heart block in a newborn if the mother is anti-SS-A
positive. It may be seen in up to
50% of SLE patients who also have Sjogren's symptoms. It may be a cause of rash with dermatitis
in a newborn if the mother is SS-A positive.
Patients who are SS-A positive may have specific skin lesions termed
subacute cutaneous lupus |
It is important to test
in mothers with recurrent miscarriages.
This may be the only positive test in ANA-negative lupus patients.
Also, it is sometimes seen in association with low platelets. |
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Anti-SS-B (anti-La) |
Antibodies to small RNA
proteins that regulate RNA polymerase 3 transcription |
Negative |
Positive |
This is seen in association
with Sjogren's syndrome and less commonly seen in SLE |
This helps with the diagnosis
of Sjogren's syndrome, but levels may fluctuate. |
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| Anti-histone antibody |
Antibody to cellular structures
called histones whose function is part of the nucleosome structure |
Negative |
Positive | Antibodies to the histone
component of the nucleus is seen most frequently in drug-induced forms of
lupus. This may occur in a patient
who is on one of the medications known to induce a lupus syndrome.
If a positive antinuclear antibody shows up, then one may perform
the anti-histone antibody test to help clarify whether this might be a drug-induced
lupus situation vs typical SLE |
It is helpful when trying
to differentiate drug-induced lupus versus idiopathic lupus. |
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Anti-cardiolipin antibody |
This is a blood test for
the presence of IgG, IgM and IgA antibodies against cardiolipin phospholipid
material in the body |
Negative, <10 units |
Positive,
High
>80 units, medium 20-80 units and low 10-20 units |
Anticardiolipin antibodies
may be found in lupus patients. In
this case there is a predilection for thrombotic events with recurrent loss
of the fetus in pregnancy and deep
vein thrombosis. Anticardiolipin
antibodies may be present in what is termed anti-phospholipid syndrome (APS)
with venous and arterial thrombotic episodes.
This may lead to stroke, coronary occlusion, avascular necrosis of
bone and recurrent loss of pregnancies |
Medium to high levels of
IgG anticardiolipin antibody are more specific for Anti-Phospholipid Syndrome
(APS). The levels should be repeated in three months
if the diagnosis (APS) is in question since certain infections can cause
positive antibodies. |
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| Lupus anti-coagulant |
This is a blood test to
identify an antibody that actually causes anti-coagulation in the laboratory
tests, but is associated with a clotting predilection with thrombosis in
the body. This may be seen in patients
with anti-phospholipid syndrome or in SLE.
It may be responsible for a false-positive report of a VDRL for syphilis |
Negative |
Positive | Positive lupus anti-coagulant
may be associated with SLE or Anti-Phospholipid Syndrome (APS) |
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| HLA-B27 |
This is a blood test that
must be received in a timely manner so that there are still viable lymphocytes
to test in the laboratory. This
test identifies the presence of the HLA-B27 antigen on the surface of the
patient's cells |
Negative result |
Positive for HLA-B27 |
90-95% of patients with
ankylosing spondylitis are HLA-B27 positive.
8% of the Caucasian population is B27 positive. Of those that carry the HLA-B27 gene, only
approximately 20% will develop a rheumatic disease. Reiter's syndrome also has approximately a 70% association with
B27. In inflammatory bowel disease
particularly with spinal involvement, B27 may be present in up to 50% of
individuals |
This test is helpful if
the diagnosis is in question, but it is not necessary for the diagnosis
of ankylosing spondylitis if diagnostic radiographs are present. It is also associated with recurrent uveitis,
an inflammatory condition of the eye |
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| Complete blood count (CBC) | This is a complete analysis
of the blood cells in the circulation including the red blood cells, white
blood cells and platelets. It also
may include a "differential" which is a percentage of the different
types of white blood cells present. Platelets which are an essential element in clotting in the body
are quantified as part of the CBC |
Hemoglobin 12-14 gm%.
White blood count greater than 4,000 per cubic millimeter.
Platelets between 150,000-450,000 |
Values that are outside
of the normal range. A hemoglobin
less than 12 gm% represents anemia. A
white blood count under 4,000 is considered leukopenia. A platelet count under 150,000 is termed
thrombocytopenia |
Anemia may be the result
of gastrointestinal blood loss. It
also may result from any chronic inflammatory disease such as rheumatoid
arthritis. It may be the result
of iron deficiency, B12 or folate deficiency.
A decreased white blood cell count may occur in patients with SLE.
It also may occur in rheumatoid arthritis patients with enlargement
of the spleen in a condition called Felty's Syndrome.
Decreased platelets may be seen as a manifestation of lupus.
All of these cellular elements may be decreased in response to bone
marrow suppression from various medications used to treat the rheumatic
diseases especially immunosuppressive drugs that have bone marrow toxicity
such as Cytoxan or Imuran for example |
If more immature polymorphonuclear
leukocytes are seen, then this may imply the presence of an infectious process.
A higher predominance of lymphocytes may be seen in a viral illness. A decreased hemoglobin and number of red
blood cells may be seen following blood loss or in chronic inflammatory
diseases |
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| Thyroid profile and
TSH |
This is a blood test that
measures levels of thyroid hormone in the free and protein bound state and
creates an index which can be used to determine if the result is normal
or not. The thyroid stimulating
hormone level (TSH) is the most sensitive way to diagnose hypothyroidism.
TSH is produced by the pituitary gland and will increase to abnormally
high levels if insufficient thyroid hormone is being produced by the thyroid
gland. Thus an elevated TSH level indicates the
presence of hypothyroidism. This
will be reduced back to the normal range with appropriate thyroid medication |
Free-thyroid index varies
depending on lab (in our lab it is 1.24 to 4.5). Total T4 levels are usually 4.5 to 12 or
12.5 mcg/100 cc. TSH level is usually
approximately 0.3 microunits per milliliter up to 4 microunits per milliliter |
TSH above the upper range
of normal usually 4.5 or higher indicates hypothyroidism. An FTI that is below the normal range (less
than 1.2) may also be consistent with hypothyroidism. A level higher than 4.5 on the free-thyroid
index may indicate hyperthyroidism |
Hypothyroidism with an
elevated TSH may be associated with various rheumatologic problems including
symptoms of fibromyalgia. Also there
is an incidence of carpal tunnel syndrome associated with hypothyroidism.
Hyperthyroidism may be associated with excessive turnover of bone
with the development of osteoporosis. Also
patients with hyperthyroidism may develop weakness in the muscles closest
to the body (myopathy) |
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| Urinalysis |
As part of the urinalysis,
a dipstick is put in the urine which indicates evidence of excess glucose
or protein present. Microscopic
evaluation is done to see if there are an abnormal number of red blood cells
or white blood cells in the urine |
No significant number of
cells seen on microscopic analysis. Negative
dipstick with no appreciable protein or glucose in the urine |
1+ or greater protein on
the dipstick is abnormal and may need to be followed up with a 24 hour urine
collection to quantitate the urine protein.
An elevated glucose in the urine needs to be correlated with a fasting
serum glucose to see if this is abnormal.
If there is a high number of white blood cells in the urine and any
history to suggest a possible urinary tract infection, then the urine may
need to be cultured for evidence of an active infection. If there are a persistent number of red blood
cells in the urine (and it is not around the time of the menstrual cycle
in a female), then further evaluation regarding the source of these red
blood cells is indicated |
Protein in the urine may
be present with any intrinsic kidney disease such as lupus nephritis. The presence of red blood cells or what are
called red blood cell casts, also may be indicative of lupus nephritis.
Protein may appear in the urine as a consequence of toxicity from
various medications including gold therapy or penicillamine |
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| Blood, urea and nitrogen
(BUN) and serum creatinine |
These are blood tests that
have to do with kidney function. The
creatinine is a more reliable assessor of kidney function when combined
with a 24 hour collection of urine with the lab calculating what is called
a creatinine clearance. This is
an earlier and more specific indicator of underlying renal dysfunction.
The BUN and creatinine are both blood tests |
The BUN level varies depending
on the lab, but may run from 7 to 8 mg% up to 26 mg%. Normal creatinine levels are 0.6 mg% up to
1.4 or 1.5 mg% depending on the lab |
Levels that fall beyond
the normal range |
With active renal disease
such as occurs with lupus nephritis, the creatinine may rise to very high
levels. Certain medications such
as cyclosporin have to be monitored closely regarding even any milder changes
in the creatinine with a subsequent lowering of the dosage of the drug. If kidney dysfunction develops and the creatinine
starts to rise, then a number of medications need to be adjusted downward
in dosage to prevent excessive levels of these medications. This would include adjustments in methotrexate
and leflunomide for example based on the creatinine level. An elevated BUN with normal creatinine may
sometimes simply indicate a state of dehydration
or excess diuresis and these situations need to be corrected |
Creatinine levels are important
to watch with patients that are on nonsteroidal anti-inflammatory drugs
especially in the elderly population where renal dysfunction may occur in
response to these medications |
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| Liver function tests, AST
(SGOT), ALT (SGPT), Alkaline phosphatase, gamma-glutamyl transpepti-dase
(GGTP) |
These are blood tests obtained
as part of monitoring liver function. This is an essential part of treatment with methotrexate and leflunomide
to make sure there is no toxicity developing |
A particular range from
that particular lab on each test |
Elevations above the upper
range of normal for that particular lab |
Elevated alkaline phosphatase
may come from liver but also may be coming from bone and special tests can
help clarify the source of the elevation. Alkaline phosphatase is an important way to monitor Paget's disease
during treatment. This test is elevated
in active Paget's disease, but with appropriate treatment this comes down
into the normal range. Transaminase
levels with elevations of the ALT and AST may be seen as a result of medications
causing liver inflammation. They may also be indicative of underlying hepatitis, such as hepatitis
C infection (which may have associated musculoskeletal symptoms such as
joint pain in conjunction with the liver abnormalities). Clinoril (sulindac) is known to cause liver
function abnormalities in a small percentage of patients and this needs
to be monitored. A common cause
of ALT/AST elevation is fatty liver, a benign condition. |
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| Calcium |
This is a blood test to
determine the serum calcium level |
Usually in the 8.5 to 10.5
mg% |
Results that fall below
or above the range of normal |
An elevated calcium may
be associated with an excess of parathyroid hormone (PTH). This may occur secondary to a tumor in the
parathyroid gland (which is located behind the thyroid gland). With an elevation of the PTH level, patients
may be predisposed to deposit calcium crystals in the cartilage of joints
(chondrocalcinosis) |
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