13. Lab Testing

Question 1

Overview: what is critical to making a rheum diagnosis? in general, what is the role of lab testing?

Answer 1

History and Physical Exam are crucial: lab testing is expensive and should be done thoughtfully, based on the clinical diagnosis

Question 2

What are the three categories of lab tests in general? A few examples for each category?

Answer 2

• Diagnostic (ANA, RF, ANCA, ACPA, HLA-B27)
• Prognostic (dsDNA Anti-SM, Jo-1 antibody)
• Evaluative (ESR, CRP)

Question 3

When a SPECIFIC test is POSITIVE, you rule in or out a disease?

Answer 3

rule IN a disease (spin)

Specificity –> NIH (Negative in Health)

Question 4

When a SENSITIVE test is NEGATIVE, you rule in or out a disease?

Answer 4

rule OUT a disease (snout)

Sensitivity –> PID (positive in disease)

Question 5

ESR: what does it test for? What affects the rate?

Answer 5

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

Question 6

Generally, what does an elevated ESR indicate?

Answer 6

a hypercoagulable state:

• malignancy
• inflammation
• infection

Question 7

ESR: what rate is considered to be hign?

Answer 7

ESR > 100 considered sign of illness (malig, inflammation, infection)

Question 8

ESR: what is its application in rheumatology?

Answer 8

• use to evaluate presenting symptoms in an overall clinical picture
• use to monitor disease activity (RA, vasculitis)

Question 9

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?

Answer 9

ESR to monitor his disease activity

Question 10

An elevated CRP should make me think what?

Answer 10

think infection

Question 11

CRP: what will cause it to be elevated?

Answer 11

any pathological condition associated with tissue destruction or inflammation.

Question 12

CRP: where is it produced? what is it produced in response to?

Answer 12

• Produced in liver
• in response to IL-1, IL-6, TNF-alpha (pro-inflammaoty cytokines)

Question 13

CRP: what would we expect this test to do after a surgery?

Answer 13

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

Question 14

CRP: application in rheumatology?

Answer 14

Use to evaluate an elevated ESR. Also use to monitor therapy.

Question 15

If ESR is high, but CRP is normal, what is our conclusion?

Answer 15

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.

Question 16

If I have an elevated CRP in a sick patient, what test should I probably also order?

Answer 16

blood cultures to further investigate possible infection

Question 17

Rheumatoid Factor: what is it?

Answer 17

Auto-antibody IgM antibody directed against the Fc (constant) portion of IgA.

Question 18

What are a few non-rheumatic conditions that will cause RF to be elevated?

Answer 18

• elev in some normal individuals (5%)
• elderly
• bacterial: endocarditis
• Viral: Hep C

Question 19

ACPA: definition?

Answer 19

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

Question 20

ACPA: what are non-rheumatic risk factors for developing these?

Answer 20

• smoking (increases citrullination of proteins in lung)
• peridontal disease

Question 21

ACPA: advantages over the RF assay?

Answer 21

• More specific for RA
• both sensitivity and specificity are higher

Question 22

ACPA: what are its uses?

Answer 22

• 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

Question 23

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?

Answer 23

ACPA is specific for RA, so get ACPA to rule it out.

Question 24

HLA-B27: define? what disease is it correlated with?

Answer 24

MHC Class I antigen, marker for the shared epitope (HLA DR4)

Associated with ankylosing spondylitis

Question 25

If imaging is positive for ankylosing spondylitis, should I still order an HLA-B27?

Answer 25

No, imaging is diagnostic, don’t need further lab tests

Question 26

If imaging is negative for ankylosing spondylitis but I have a strong clinical suspicion, can HLA-B27 help me?

Answer 26

Yes, it can help clarify what is going on even if imaging studies are negative.

Question 27

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?

Answer 27

He has axial involvement so an HLA-B27 can be helpful here.

Question 28

in what way is HLA-B27 not helpful (is it positive in a certain % of the population regardless of disease)?

Answer 28

Positive in 8% of caucasians, so a positive test without clinical sx does not mean someone has ank spond.

Question 29

ANA tests: positive in what disease state? sensitive? specific?

Answer 29

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.

Question 30

what are anti-DNA and anti-SSA antibodies?

Answer 30

subsets of ANAs:

Anti-DNA antibodies detect lupus nephritis

Anti-SSA antibodies detect neonatal lupus

Question 31

What are the 2 current tests that we have for evaluating ANAs?

Answer 31

• IIF
• ELISA

Question 32

IIF vs ELISA: which gives you more information?

Answer 32

IIF because it localizes the antigen within the tissue rather than just indicating its presence.

Question 33

IIF: what level is considered significant?

Answer 33

1:160 or higher is clinically significant

Question 34

IIF: what staining pattern is specific for SLE?

Answer 34

peripheral/rim pattern

Question 35

IIF: what staining pattern is most common (and also least specific)?

Answer 35

speckled pattern

Question 36

What test result does this depict?

What are the staining patterns in each picture?

What disease does each pattern indicate?

Answer 36

P = peripheral (specific for LUPUS)

D = Diffuse (not specific)

S = Speckled (common, least specific)

N = nucleolar (scleroderma)

Question 37

What staining pattern is depicted? what disease does it indicate?

Answer 37

Centromere staining.

Indicates scleroderma

Question 38

What two tests do we have for ANCAs?

Answer 38

cANCA (cytoplasmic, for PR3)

pANCA (perinuclear, for MPO)

Question 39

What staining patterns are depicted in these pictures? What disease states are likely?

Answer 39

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

Question 40

If you order a pANCA or cANCA, what else MUST you test for before you can make a diagnosis?

Answer 40

Both antibody and antigen must be tested for.

With cANCA, also test for PR3.

With pANCA, also test for MPO

Question 41

Positive ANA in a rim pattern suggests what diagnosis?

Answer 41

SLE

Question 42

Positive ANA in a centromere pattern suggests what diagnosis?

Answer 42

CREST variation of scleroderma

Question 43

anti-double-stranded DNA is specific for what disease?

Answer 43

lupus

Question 44

What test, when performed serially over time, helps us manage patients with lupus?

Answer 44

Anti-dsDNA (ANA)