MSK labs & imaging Flashcards
When is testing for musculoskeletal disorders indicated?
● Testing should be reserved for symptomatic patients.
● Some labs can and do come up positive in asymptomatic patients.
○ E.g. A low titer ANA can be positive in up to 30% of healthy people
(and decreases with high titers), depending on the technique
used
Antinuclear Antibody (ANA) test
The ANA (Antinuclear Antibody) is a screening test that detects the presence of autoantibodies. Autoantibodies are
a diverse group of antibodies that react with antigens within the
cell nucleus that can be seen with autoimmune diseases.
Primary method of testing for ANA
Immunofluorescence Microscopy
Interpretation of an ANA test
○ The ANA is a nonspecific test and can be positive in nearly 30% of
healthy individuals at low titer (percentage lowers with higher titer ANA)
○ This is a sensitive test. Individuals with active connective tissue
diseases, like Systemic lupus erythematosus, will generally have a positive ANA. Active connective tissue disease will rarely have a
negative ANA - these are determined clinically on a case by case basis.
■ This is unlike RA where disease can be present with negative RF and negative CCP.
Antinuclear Antibody (ANA)
Approach to assessment
● For patients that are suspected of Lupus and other connective tissue
disorders the healthcare provider needs to conduct a thorough patient history
and PE prior to testing
If connective tissue disorders are suspected consider ordering:
○ ANA with reflex for IFA (for titer) rather than an ANA direct
○ Comprehensive/ENA ANA (to assess for positive dsDNA, RNP, etc)
○ Specific tests based on hx and PE (e.g. SSA and SSB for Sjogren’s)
○ Screening with a CBC and UA may also be useful
○ Consider screening using the ACR/EULAR 2019 SLE Criteria
What does titration mean in relation to ANA?
● Antibody Titer Definition: The amount of a specific antibody present in the
bloodstream.
○ A higher titer can be seen with more active disease, more likely a disease
is present, and in some cases the more recent an exposure has been.
● Examples of this can be seen with the ANA (e.g. low 1:80 - high 1:1280), RF, CCP, etc.
Patterns of ANA fluorescence
● A: Rim (peripheral)
○ Associated disorders: SLE
● B: Homogeneous (diffuse)
○ Associated disorders: SLE, drug induced
lupus, dermatomyositis
● C: Speckled
○ Associated disorders: SLE, cutaneous
lupus, Sjogren’s, MCTD, Polymyositis,
Systemic sclerosis
● D: Nucleolar
○ Associated disorders: Systemic sclerosis,
Polymyositis overlap
● Other: Centromere
○ Associated disorders: Limited scleroderma
(CREST)
T/F A positive ANA means there is active disease
F
Rheumatoid Factor (RF)
: The RF is an autoantibody that binds to the
Fc region human immunoglobulin G (IgG). The RF that
binds to IgG may be of any isotype: IgM (most common),
IgG, IgA, or IgE.
Method of testing for RF factor
Latex fixation, titers >1:20 are positive
Interpretation of Rheumatoid Factor (RF)
The RF has a 70% sensitivity, but can be as low as 26-60%. A positive RF is not
specific for RA. A positive RF can be seen in rheumatic diseases, but can also be
seen in non-rheumatic diseases. With a positive RA dx, a high titer (1:640) RF has
high specificity and is associated with more severe RA
Rheumatic Diseases associated with a positive RF
○ Rheumatoid arthritis, Sjogren’s syndrome, Mixed connective tissue disease, Mixed
cryoglobulinemia (types II and III), Systemic lupus erythematosus, Polymyositis or
Dermatomyositis
Non-rheumatic Diseases associated with a positive RF
○ Infection: Bacterial endocarditis, Hepatitis B or Hepatitis C, Tuberculosis, Syphilis, Parasitic diseases, Leprosy, Other viral infection
○ Pulmonary Disease: Sarcoidosis, Interstitial pulmonary fibrosis, Silicosis, Asbestosis
○ Misc Diseases: Primary biliary cholangitis, Malignancy, After multiple immunizations
Anti-Citrullinated Peptide Antibodies (Anti-CCP)
The Anti-CCP are autoantibodies directed against the amino acids formed by the posttranslational modification of arginine by the enzyme peptidylarginine deiminase (PAD) into citrulline.
Method of testing for Anti-Citrullinated Peptide Antibodies (Anti-CCP)
ELISA
Interpretation of Anti-CCP
The Anti-CCP have a similar sensitivity to the RF (67%), but
has an increased specificity (97%). This is more useful in the diagnosis of RA.
Anti-CCP are more associated with erosive disease rather than RF. There is
some speculation that the Anti-CCP may have a role in the pathogenesis of
RA and can be triggered by environmental factors like smoking.
Erythrocyte Sedimentation Rate (ESR)
The ESR is an indirect measure of alterations in immunoglobulins
and acute phase reactants, that are synthesized in the liver, in response to
inflammation. This is considered a measure of chronic inflammation.
Acute Phase Reactants of inflammation:
Fibrinogen, Plasminogen, Ferritin, C-reactive
Protein (CRP), Albumin, others.
Method of testing for Erythrocyte Sedimentation Rate (ESR)
Westergren, erythrocyte sedimentation is measured after 1 hour
○ Note: Normal values are not adjusted for age and sex. The ESR
increases with age and is slightly higher in females. Adjustments are
needed to fully assess the upper limit of an ESR.
ESR in women vs. men
ESR in Women = (Age + 10) / 2
ESR in Men = Age / 2
Explain the rise and Fall pattern of ESR
○ The ESR can rise over days to weeks and fall over days to weeks
○ This depends on what is causing the inflammation and varies from
person to person
■ Diabetes, smoking, obesity
Interpretation of ESR:
The ESR is sensitive for most types of inflammation, but is not specific.
■ A normal value can help to rule out inflammatory disorders, but an
increased value can be confusing.
■ A thorough history, PE, and at time additional testing are all needed
to assess the utility of the ESR.
Conditions that can increase the ESR:
Increased ESR (any condition that increases fibrinogen):
■ Can be seen in bacterial infections, connective tissue disease, inflammatory disorders, and malignancy; but can also be seen in diabetes, smoking, obesity, end stage renal disease, pregnancy, and possibly race
Conditions that can decrease the ESR:
Aka causes decreased fibrinogen
Congestive Heart Failure, sickled erythrocytes, and the presence of
cryoglobulins
C-Reactive Protein (CRP)
The CRP is an acute phase reactant that is synthesized in response to tissue injury. This is considered a measure of acute inflammation.