Rheumatologic Disorder Diagnostic Studies Flashcards
what are the two acute phase reactants
Acute phase reactants
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- serum proteins which increase in concentration during inflammation (synethsized from the liver and release during ANY inflammation)
- this can be chronic or acute inflammation
- these proteins are released as a result of driving factors during inflammation : namely IL-6 (others: Il-1 beta, TNF-alpha & interferon gamma)
C-Reactive Protein & Erythrocyte Sedimentation Rate
Triggers include: chronic and acute infmallation
- trauma
- infection
- ischemia/infarction
- malignancy
- systemic autoimmune and inflammatory disease
- immun reactions to drugs/vaccines
CRP: what is it and how is it tested
CRP: C reactive protein
- predominatly synthesized in the iver
rises and falls MUCH more rapidly than ESR
- rises within 4 hours of tissue injury, peaks 24-72 hours
- without continued inflammatory trigger: falss within 18hours (rapid)
Factors which influence CRP
- age
- obesity
- race
- gender
thus, ULN can be higher in obese, female, older & black individuals
ESR
what is it
influenced by
how its tested
ESR: erythrocyte sedimentation rate
westergren ESR = gold standard
this is an INDIRECT measure of inflammation
ESR: the distance the RBC’s fall within a test tube over a given period of time
- RBC’s naturally are negative, thus they repell each other and fall slowly, less distance covered in an amount of time = lower ESR
- when acute phase reactants are present, they are postive; thus they wrap around RBC’s and make them clump together
- RBC clumed together(rouleaux formation) , therefore thye fall faster and thus a further distance = larger number
ESR seems to stay elevated for a longer time that the CRP
Things that can falsely elevated ESR?
things that can falsely lower ESR?
False Elevation of ESR (anything with extra proteins from inflammation will increased ESR)
- age (ULN in men is (age)/2) while (ULN in women is age+10/2)
- pregnancy
- gender (women)
- anemia: less RBC, less repeling, fall faster = elevated
- paraproteinemia
- kidney or thyroid disease
- obesity
- tilting of tube or high room temp in lab
False Lowering of ESR
- RBS disorders (sickle cell)
- polycythemia
- heart failure
- liver faiure (theres no proteins at all, so its so low)
- extreme leukocytosis
- extremely high bile salts
- clotting of sample or low temp in room
DDX. for a HIGH ( > 100) ESR
what about a LOW ( 0) ESR
HIGH: > 100 ESR
- infection, bacterial
- connective tissue dissue disease: giant cell arteritis, polymyalgia, SLE or other vasculitis: lots of inflammation!
- malignancy: lymphoma, myleoma (protiens!)
LOW: 0 ESR
- afibrinogenemia/dysfibrinogeneia (so sick they have no fibrinogen, no ability for clot, cant repel each other, barely fall)
- extreme polycythemia
- increase plasma voscoisty
what is Rheumatoid factor
when is it postive/indicating
RF: an autoantibody directed against the Fc fragment of immunoglobolin G (antibody against an antibody)
the autoantibody “ the RF” can come from any of the following anitbodies of self
- IgM
- IgG
- IgA
- IgE
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RF can be postivie in a variety, or virtaully any inflammatory condition
- RA: common
- Hep C: Chronic
- SLE, slecrosis, mixed tissue disease, sjogren’s sarcoidosis
- neoplasms (after radiation/chemo)
- infections: AIDS, mono and parasites
- chronic viral infections
- Hep B/C
- Cryoglobulinemia
sometimes, RF is postivie in the absence of any disease processes
- seen in older adults (> 70 y/o)
IN SUM
- elevated RF is like not a big deal if its above ULN, but when its SIGNIFICANTLY above, thats when you think of something
Anti-CCP
- what are they
- what may thye indicate
Anti-CCP
- antibody to cyclic citrullinated peptide
what is it
- citrullination is a conversion of amino acid arginine into citruilline
- some people make antibodies against these cirutillinated protein
- this is more specific in the diagnosis of RA
in RA: check RF but check anti-CCP for sure
Antinuclear Antigen Test (ANA)
what is it
method of testing
patterns of findings (5)
what is it
- a test which detects antibodies made to ANY antigen present within the nucleus
- this is nonspecific: can be literlaly any antibody made against some aspect of the nucleus
Method of Testing
- preferred method = indirect immunoflorescnce test
prepped two slides of cells: serum poured over cells, then immunoflor. poured over with tagged antibodies to light up the seurm ab. if they match
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Patterns of ANA
- Rim (peripheral)
- homogenous (diffuse)
- speckled
- nucleolar
- Centromere
ANA: conditions associted with postive ANA findings
some poeple may have postive ANA without disease!!
Most Commonly: SLE is associated with a postive ANA (almost ALL lupuse pt. will have a postive ANA)
but… other conditions can have + ANA
- connective tissues (mixed)
- autoimmune liver disease
- systemic sclerosis
- antiphospholipid syndrome
- sjogrens
- polymyositis
- the list goes on…..
how can ANA patterns/findings be broken down further to test for “specific” disease
ANA: broken into patterns (diffuse, speckled, etc.) can FURTHER be broken into the extractable nuclear antigens
Homogenous (diffuse) pattern
- DNA-histone = SLE
- Mi-2 = dermatomyositis
Rim
- ds-DNA = SLE
Speckled
- ss-A = SLE
- ss-B = SLE
- RNP
- Sm
Nucleoar
- topoisomerase I
- RNAP III
etc…..
you can individaully test these specific extractable antigens for further testing of disease
ANA antigens specific (aka most commonly found) to the following conditions
- SLE
- RA
- mixed connective tissue
- diffuse systemic sclerosis
- limited systemic sclerosis
- primary sjogrens
reminder: these are ANA antibodies subcategories of which antigen they directly taget
SLE
- dsDNA
- smith ab also seen
- chromatin
RA
- rarely see ANA
Mixed Connective Tissue Diseae
- RNP
Diffuse systemic sclerosis
- sometimes RNP, SS-A or centromere (not great findings)
Limitied systemic sclerosis
- Centromere
Primary Sjogrens
- SS-A
- SS-B
Scleroderma
- centromere B
Polymyositis/dermatomyositis
- Jo-1
how would an ANA panel be ordered & what would your index for suspision be
even if the ANA comes back as high, your index is still low as lots of thigns can produced high ANA
- high ANA does not automatically make you think of a rheumatic disorder
Ordering
- you would get the ANA and then usually labs would reflex if the ANA is high - go ahead and run a set panel fo specific antigens the antibodies are targeting
- example: smith, dsDNA, SS-A, SS-B, centromere
Antiphospholipid antibody testing in Rheum
what is it specifcally testing for
APA in rheumatology specifically is tesing for
- Beta 2 Glycoprotein antibodies
- anti-cardiolipin antibodies
- lupuse anticoagulant
Lupuse Anticoagulant
- can falsely prolong the PTT but can also cause clotting (?)
- this can be impacted by anti-coagulation medications
anti-glomerular basement membrane antibody
anti-parietal cell antibody
Anti-GBM antibody
- seen in goodpastuers syndrome: attacking basement membrane in KIDNEYS and LUNGS
- hemoptysis & diffuse alveolar hemorrhage
- acute reanl failure from the glomerurolnephritis
Anti-parietal cell antibody
- autoimmune atrophic gastrisis (AAG) and pernicous anemia (PA) can have this
- difficut to absorb Vit B12: ebacuse there are antibodies destorying the parietal cells
- GI doctors/hem. would order this
