Overview: what is critical to making a rheum diagnosis? in general, what is the role of lab testing?
History and Physical Exam are crucial: lab testing is expensive and should be done thoughtfully, based on the clinical diagnosis
What are the three categories of lab tests in general? A few examples for each category?
-Diagnostic (ANA, RF, ANCA, ACPA, HLA-B27)
-Prognostic (dsDNA Anti-SM, Jo-1 antibody)
-Evaluative (ESR, CRP)
When a SPECIFIC test is POSITIVE, you rule in or out a disease?
rule IN a disease (spin)
Specificity --> NIH (Negative in Health)
When a SENSITIVE test is NEGATIVE, you rule in or out a disease?
rule OUT a disease (snout)
Sensitivity --> PID (positive in disease)
ESR: what does it test for? What affects the rate?
tests for speed of sedimentation of RBCs (mm/hour).
Measures interaction of acute phase proteins and RBCs
Affected by shape of RBCs, number of RBCs, fibrinogen, hypergammaglobulinemia, anemia, age, pregnancy
Generally, what does an elevated ESR indicate?
a hypercoagulable state:
ESR: what rate is considered to be hign?
ESR > 100 considered sign of illness (malig, inflammation, infection)
ESR: what is its application in rheumatology?
-use to evaluate presenting symptoms in an overall clinical picture
-use to monitor disease activity (RA, vasculitis)
Case: 65 yo man with polymyalgia rheumatica (variant of RA) has decreased his dose of prednisone, but is now experiencing increased symptoms. Should he incr his dose of prednisone? what test might you run to check on the progression of his disease?
ESR to monitor his disease activity
An elevated CRP should make me think what?
CRP: what will cause it to be elevated?
any pathological condition associated with tissue destruction or inflammation.
CRP: where is it produced? what is it produced in response to?
-Produced in liver
-in response to IL-1, IL-6, TNF-alpha (pro-inflammaoty cytokines)
CRP: what would we expect this test to do after a surgery?
Levels generally rise 4-6h after tissue injury (ie surgery)
Levels then return to normal within a week assuming there are no post-op complications
CRP: application in rheumatology?
Use to evaluate an elevated ESR. Also use to monitor therapy.
If ESR is high, but CRP is normal, what is our conclusion?
NOT inflammatory because CRP is normal. But ESR is high so there is something going on: may be hypergammaglobulinemia since that would raise ESR but not CRP.
If I have an elevated CRP in a sick patient, what test should I probably also order?
blood cultures to further investigate possible infection
Rheumatoid Factor: what is it?
Auto-antibody IgM antibody directed against the Fc (constant) portion of IgA.
What are a few non-rheumatic conditions that will cause RF to be elevated?
-elev in some normal individuals (5%)
-Viral: Hep C
antibody to citrullinated proteins. these proteins occur all over the body, and are non-pathological. developing antibodies to them is the pathology and is unique to RA
ACPA: what are non-rheumatic risk factors for developing these?
-smoking (increases citrullination of proteins in lung)
ACPA: advantages over the RF assay?
-More specific for RA
-both sensitivity and specificity are higher
ACPA: what are its uses?
-identifying early inflammatory arthritis pts
-evaluating arthritis pts with negative RF
-evaluating pts who have positive RF but don't have clinical signs of arthritis
Case: you have a patient who appears to have generalized osteoarthritis, with some joint deformities and some arthralgia. Her RF is elevated. How could you support your opinion that her RF is elevated due to age rather than development of RA?
ACPA is specific for RA, so get ACPA to rule it out.
HLA-B27: define? what disease is it correlated with?
MHC Class I antigen, marker for the shared epitope (HLA DR4)
Associated with ankylosing spondylitis
If imaging is positive for ankylosing spondylitis, should I still order an HLA-B27?
No, imaging is diagnostic, don't need further lab tests
If imaging is negative for ankylosing spondylitis but I have a strong clinical suspicion, can HLA-B27 help me?
Yes, it can help clarify what is going on even if imaging studies are negative.
Case: 25 yo with chronic lower back pain. Prior imaging was positive for a disc bulge, but current imaging is normal. Can I order any test to clarify his problem?
He has axial involvement so an HLA-B27 can be helpful here.
in what way is HLA-B27 not helpful (is it positive in a certain % of the population regardless of disease)?
Positive in 8% of caucasians, so a positive test without clinical sx does not mean someone has ank spond.
ANA tests: positive in what disease state? sensitive? specific?
positive in 98% lupus patients.
sensitive but not specific:
if positive, could mean a lot of things.
if negative, pt is unlikely to have lupus.
what are anti-DNA and anti-SSA antibodies?
subsets of ANAs:
Anti-DNA antibodies detect lupus nephritis
Anti-SSA antibodies detect neonatal lupus
What are the 2 current tests that we have for evaluating ANAs?
IIF vs ELISA: which gives you more information?
IIF because it localizes the antigen within the tissue rather than just indicating its presence.
IIF: what level is considered significant?
1:160 or higher is clinically significant
IIF: what staining pattern is specific for SLE?
IIF: what staining pattern is most common (and also least specific)?
What test result does this depict?
What are the staining patterns in each picture?
What disease does each pattern indicate?
P = peripheral (specific for LUPUS)
D = Diffuse (not specific)
S = Speckled (common, least specific)
N = nucleolar (scleroderma)
What staining pattern is depicted? what disease does it indicate?
What two tests do we have for ANCAs?
cANCA (cytoplasmic, for PR3)
pANCA (perinuclear, for MPO)
What staining patterns are depicted in these pictures? What disease states are likely?
Left: cANCA (cytoplasmic). Wegener's granulomatosis (aka GPA) **know this association for sure!
Right: pANCA (perinuclear). less specific, but associated with microscopic polyangiitis and pauci-immune glomerulonephritis
If you order a pANCA or cANCA, what else MUST you test for before you can make a diagnosis?
Both antibody and antigen must be tested for.
With cANCA, also test for PR3.
With pANCA, also test for MPO
Positive ANA in a rim pattern suggests what diagnosis?
Positive ANA in a centromere pattern suggests what diagnosis?
CREST variation of scleroderma
anti-double-stranded DNA is specific for what disease?
What test, when performed serially over time, helps us manage patients with lupus?