Rheumatology Labs
Brenda Beckett, PA-C
Clinical Assessment II
Rheumatology
Evaluation of the patient with a
suspected rheumatologic disorder is
dependent upon an initial clinical
suspicion, a thorough history and
clinical evaluation, and laboratory
testing.
Collagen Vascular Disorders
Considerable overlap exists in the clinical
features of these disorders as well as in the
presence of the various antibodies.
(nonspecific)
• Systematic approach to the laboratory
diagnosis will more often result in a correct
diagnosis and in many instances shorten the
time and decrease the expense incurred
before appropriate therapy can be initiated.
•
Antinuclear Antibodies (ANAs)
Group of antibodies directed against
proteins in cells.
 ANA test is not specific to any one
antibody (but it is sensitive to SLE)
 Multiple follow-up tests to confirm
positive

Antinuclear Antibody (ANA)
Initial screening test used in the evaluation of
patients with a suspected collagen vascular
disease (RF should also be tested for in
adults with arthritis).
• ELISA or other screen to rule out negatives.
• Positives are tested by indirect
immunofluorescence, have patterns that are
easy to read.
•
Antinuclear Antibody (ANA)
Titer greater than or equal to 1:160 is
considered a significant positive.
• Titers less than or equal to 1:80 are usually of
no or questionable significance.
• Positive ANA incidence is 99% in SLE, 85%
in Sjögren's, 88% in scleroderma, 55% in
rheumatoid arthritis, and 40% in juvenile
rheumatoid arthritis.
•
Antinuclear Antibody (ANA)
The ANA consists of antibodies of
different specificities. There is
controversy about the usefulness of
determining the pattern of
immunofluorescence staining of the
ANA and the relationship of the pattern
to antibody specificity and disease
state.
Generalizations Regarding ANA
Patterns

Peripheral (Rim) Pattern of Staining
– suggests anti-DNA antibodies, seen most
often in SLE.

Homogeneous Staining
– suggests anti-DNA, anti-histone, or antideoxyribonucleoprotein (DNP) antibodies
observed in SLE, RA, and drug-induced
SLE.
Generalizations Regarding ANA
Patterns

Speckled Pattern
– (1) Antibody to SSA or SSB, observed in
SLE and SS
– (2) Smith antibody (Sm) observed almost
exclusively in SLE
– or (3) RNP antibody observed in SLE,
MCTD, RA, and scleroderma
Generalizations Regarding ANA
Patterns

Anti-nucleolar Staining
– observed in scleroderma and some forms of Raynaud's
phenomenon.

Centromere Pattern
– observed in the CREST syndrome of scleroderma
• Calcinosis
• Raynaud's phenomenon
• Esophageal hypomotility
• Sclerodactly
• Telangiectasia
ENA

Extractable Nuclear Antigen Antibodies.
(RNP – Ribonucleic Protein, Smith,
Scleroderma, SSA and SSB – Sjögren’s
Antibodies).

Antibodies to nuclear antigens are
hallmarks of collagen vascular diseases
ENA
Sm - Specific for SLE
 SSA (Ro)- SLE, Sjögren’s
 SSB (La)- SLE, Sjögren’s
 RNP - SLE, Sjögren’s, Scleroderma
 Scl-70 - Scleroderma, some Sjögren’s
 Jo-1 - Polymyositis/dermatomyositis

dsDNA
Double stranded DNA antibody
 High titers in SLE
 RA, Sjögren’s

ssDNA test also positive in SLE, but not
as specific
Rheumatoid Arthritis (RA)

Immunologic expression of an individual's
immune system reaction to the presence of
an immunoglobulin molecule that is
recognized as "non-self."
 This response to the "non-self"
immunoglobulin results in the presence of
immune complexes. These, in turn, bind
complement and may eventually lead to
synovium, cartilage, and bone destruction
Rheumatoid Factor (RF)

RFs are immunoglobulins directed against
portion of IgG

RF may be found in a variety of autoimmune
diseases, as well as in up to 10% of
apparently healthy individuals.

May be positive in some patients with
syphilis, viral infections, chronic liver
diseases, sarcoidosis, leprosy, neoplasms,
and a variety of other chronic inflammatory
conditions (nonspecific)
Rheumatoid Factor

High concentrations of RF (>300 IU/mL) are
found with RA and Sjögren's syndrome.

Juvenile onset RA is less likely to have a
positive test for RF.

The RF test should be used with caution in
the diagnosis of RA because of the low
predictive value of the test for this disease.
The percentage of positive RF assays in the
normal population increases with age.
Anti-CCP





Anti-cyclic citrullinated peptide (immune
protein)
As sensitive as, and more specific than RF in
early and fully established disease
May predict RA in undifferentiated arthritis
A marker of erosive disease in RA
May be detected in healthy individuals years
before onset of RA
Antineutrophilic Cytoplasmic
Antibodies (ANCAs)
Important for the diagnosis of certain
vasculitis syndromes (Wegener’s
granulomatis)
 cANCA (cytoplasmic)
 pANCA (perinuclear)
 Also positive in RA, SLE, myositis,
infections, GI disease, etc

HLA B27
Human Leukocyte Antigen B27
 90% of patients with Ankylosing
Spondylitis have HLA B27
 Only small amount of patients with HLA
B27 will have disease
 Can also be at risk for Reiter’s, IBD,
Psoriatic Arthritis

C-reactive Protein (CRP)
Protein that binds to polysaccharides present
in many bacteria, fungi, and protozoal
parasites. It also binds to phosphocholine,
lecithins, and polyanions such as nucleic
acids. Once complexed, CRP becomes an
activator of the classical complement
pathway. CRP recognizes potentially toxic
autogenous substances released from
damaged tissues, binds them, and then
detoxifies or clears them from the blood.
C-reactive Protein (CRP)
CRP is the most sensitive acute phase
protein. CRP will elevate within two
hours of acute insult (surgery, infection,
etc.) and should peak and begin
decreasing within 48 hours if no other
inflammatory event occurs.
C-reactive Protein (CRP)
•
Dramatic increases following MI, trauma,
infection, surgery, or neoplastic proliferation.
•
In patients with rheumatoid arthritis,
persistently elevated CRP concentrations are
present when the disease is active and
usually fall to normal during periods of
complete remission.
Erythrocyte Sedimentation Rate
(ESR)

Nonspecific marker of inflammation.
Generally, ESR does not change as
rapidly as does CRP, either at the
beginning of inflammation or as it
resolves. CRP is not affected by as
many other factors as is ESR, making it
a better marker of inflammation. Many
clinicians still use ESR as an initial test
due to its wide availability and low cost.
Synovial Fluid
Lubricates cartilage in joint space
 Normal:

– Small amount
– Clear, acellular (low WBC count)
– High viscosity
– Does not clot
– Protein = 1/3 plasma protein
– Glucose approximates plasma glucose
Synovial Fluid
Detect inflammation, infection
 Crystals

– Monosodium urate – gout
– Calcium pyrophosphate - pseudogout
Gout
Synovial fluid analysis – to detect
monosodium urate crystals.
 Serum Uric Acid may be elevated
 Urine Uric Acid may be elevated
 Kidney function tests – to determine if
uric acid crystals are accumulating in
the kidneys and impairing their function.

Monosodium Urate Crystals
Case Study
History and Presentation
 60 yo female admitted cc of generalized
weakness x2wks, morning stiffness both
knees, aggravated by movement. Mild
fever. Lost 10lbs in one mo. No
significant medical hx, except similar
episodes 2x in past year, involving
hands and wrists - took NSAIDS.
Case Study
Physical Exam
 A&O, mild distress. BP 120/80, HR 85,
T 1000F, RR 20. Abd soft, nontender,
mild splenomegaly. Knees swollen bilat,
warm, painful with movement. Mild
atrophy of forearm muscles with small
subcu firm nodules in posterior
forearms. Swelling of MCP joints.
Case Study

X-ray of hand taken:

Showed periarticular osteoporosis, bone
and cartilage destruction, joint space
narrowing.
Case Study

Differential Diagnosis?
Case Study

What lab tests do you want to order?
Lab Results
Case Study

What is your diagnosis?

What other test would you consider
performing to verify your diagnosis?

-
What else should we follow-up on in this
patient?