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.
Method of testing for CRP
Immunoassays (ELISA) and nephelometry
○ Note: The CRP is not adjusted for age. Adjustments are needed to assess
the upper limit of the CRP.
CRP in women vs. men
CRP in Women = (Age + 30) / 50 CRP in
Men = Age / 50
Explain the rise and fall pattern of CRP
This can increase over 4-6 hours and normalize within a week.
Conditions that can influence the CRP:
○ The CRP can be increased in bacterial infection, heart disease, systemic
vasculitis, acute polyarticular crystal disease, widely metastatic cancer.
○ The CRP can also be increased by age, gender, obesity, diabetes, and
cigarette smoking
Uric Acid definition
The breakdown of purines in certain foods leads to the uric acid in the
blood
Uric acid testing method
Uricase
Interpretation for the uric acid test
Increased serum uric acid levels are associated with gout, but this can be difficult determine as gouty flares can also be associated with normal to low uric acid levels. Asymptomatic Hyperuricemia can also be seen. A uric acid level can be used to monitor patients with gout with the goal of therapy being < 6.0.
A definitive dx of Gout is confirmed by ____
needle shaped negatively birefringent
crystals from aspiration or visible tophi on PE.
Human Leukocyte Antigen B27 (HLA-B27)
HLA-B27 is a protein found on the surface of white blood cells. This genetic marker is found in about 3-8% of the population. It is more highly associated with Ankylosing Spondylitis (90%) and other
spondyloarthropathies (50-80%)
Method of testing for Human Leukocyte Antigen B27 (HLA-B27)
PCR
Interpretation of Human Leukocyte Antigen B27 (HLA-B27)
A positive HLA-B27 test is not diagnostic, but can help with building a diagnosis. A negative test does not exclude a diagnosis. A thorough Hx, PE, and imaging (X-ray and MRI) can help to address the utility of HLA-B27 testing.
Antineutrophil Cytoplasmic Antibody
ANCAs are antibodies directed against antigens present in the cytoplasm of
neutrophils and monocytes.
ANCA Panel Components
○ P-ANCA (Perinuclear staining, MPOS)
○ C-ANCA, (Cytoplasmic staining, PR3S)
○ GBM (Glomerular Basement Membrane)
Dexa Scan
- Nuclear medicine study using a bone mineral density
measurement of spine and hips - Early detection of Osteopenia vs Osteoporosis
- Fractures common after 50 years of age
- Prevention of debilitating fractures
Dexa Scan USPSTF guidelines
- Begin screening women age > 65 yo and those younger who maybe at higher risk. Male screening
recommendation is indeterminate. - Dexa scan is measured as a SD above or below the norm
What is the Fracture Risk Assessment Tool
(FRAX) ?
calculates the 10 year probability of fracture. Patients that are at high risk are generally started on bisphosphonate therapy, usually
Alendronate (Fosamax).
An increased FRAX score is indicated by:
○ >20% 10 year risk for a major osteoporosis related fracture
○ >3% risk for a hip fracture
Fluoroscopy
- Radiologic imaging technique- radiation exposure
- Used for point of care imaging
- Images can be viewed in real time
- Joints can be seen in motion
- Used for hardware placement during surgery
- Can be used with contrast, but more often this is for
vascular structures
Arthrography
- Image a joint with contrast injected into the joint
- Contrast used with CT or MRI
- Makes it more complex and ↑ risk with contrast
Examples of use - Shoulder labral or rotator cuff tears
- Hip labral tears
- Wrist cartilage or ligament injury
Bone Scintigraphy
- Nuclear medicine
- IV injection of radioactive agent
- Commonly technetium Tc 99m-methylene diphosphonate
- Will show areas of increased metabolic activity
- Specifically looking for fracture healing, infection and metabolic bone
disease - Also used for tumor detection and metastatic disease
- Non-specific and does include radiation exposure
Examples of ultrasound use in Orthopedics
- Joint effusions
- Evaluation of tendons and ligament injury
- Soft tissue mass
- US guided joint injections
- Infantile hip dysplasia
PET Scan
- Positron Emission Tomography
- Often combined with CT, referred to as a PET-CT
- Most often looking for tumors and cancer
- Used across the board in oncology
Usefullness of the Rosenberg (Tunnel view) xray of the knee
- weight bearing view to all for visualization of the femoral tunnel
- Assess joint space narrowing and
osteoarthritis
Synovitis
inflammation of the synovial membrane of joints, is a manifestation of
autoimmune disease (e.g. Rheumatoid Arthritis, Gout, SLE, etc).
Over time synovitis can affect joints and _____ can develop
erosions
Marginal Erosions
○ The term “Juxtaarticular” is
also commonly used
○ “Punched out” lesions are
also used
Central erosions can be seen often with _____
Peripheral: Erosive Osteoarthritis
○ “Gull wing” deformity
Psoriatic Arthritis xray findings
Boney erosion and resorption
are sometime seen together
resulting in the classic
“Pencil-in-Cup” deformity
Types of erosions seen with RA
Marginal Erosions
○ The term “Juxtaarticular” is
also commonly used
○ “Punched out” lesions are
also used
“Pencil-in-Cup” deformity is seen with
Psoriatic Arthritis
Gout xray findings
● Well demarcated erosions away from
the joint line
○ Some with overhanging edges
and adjacent hazy tophaceous
material
○ Terms like “Rat / Mouse Bite” or
“Punched out” lesions are also
used (these can also be seen
with RA)
Ankylosing Spondylitis xray findings
● Symmetric erosions to sacroiliac
joints
○ Occasionally can be unilateral
with appropriate clinical
suspicion
● Ankylosing or “bambooing” of the
spine due to calcification of the
intervertebral disc rings, also known
as syndesmophytes
Symmetric erosions to sacroiliac
joints can be seen with _____
Ankylosing Spondylitis
These Tends to affect the spine
asymmetrically
Psoriatic Arthritis,
Enteropathic Arthritis, Reactive
Arthritis
Indications for Joint Fluid Analysis
- Crystal Analysis- Crystal Deposition Diseases
- Septic Arthritis
- Hemarthrosis
Septic Joint causes
– Direct inoculation
– Hematogenous spread
– Extension from local bone infection
What to order When you suspect septic arthritis
In addition to the joint aspiration with fluid analysis, typically order
* Joint X-rays
* C-Reactive Protein (CRP)
* not the heart one
* Erythrocyte Sedimentation Rate (ESR)
* WBC w/differential
* Blood Culture
Septic Joint treatment
- IV Antibiotics
- Surgical decompression and
lavage (or a washout) - Second option maybe needle
aspiration and lavage - With a chronic periprosthetic
infection, may need revision of
the joint
Birefringence
Optical property of the material under polarized light microscopy
Most common bacteria in septic joints
Staphylococcus
