Clin Lab: MSK 1 Flashcards
Signs that are evidence of synovitis
swelling, warmth, tenderness
burning” pain, or accompanied by numbness/tingling is more likely…
neuropathic pain
Pain accompanied by weakness is more likely…
muscle or nerve issue
Worse after inactivity is more likely…
inflammatory disorder (RA, psoriatic arthritis, lupus, etc)
Worse with activity, better with rest is more likely…
osteoarthritis
(tends to be worse on one side)
Symmetric joint involvement more likely…
systemic illness
Duration of pain that is associated with a viral/reactive cause…
< 3weeks
Duration of pain that is less likely to be a viral/reactive cause…
> 6 weeks
*think more long term chronic things like RA
Symptoms more associated with systemic illness
- fever
- night sweats
- skin manifestations (lupus or scleroderma)
- adenopathy
An younger/middle aged patient w/ joint pain think…
Lupus
An older patient w/ joint pain think…
OA
Monoarticular conditions
- OA
- Injury
- Septic arthritis*
- Crystal-induced (gout, CPPD)
- Neoplasms
What is so important about septic arthritis?
It is a MEDICAL EMERGENCY
Polyarticular w/ synovitis conditions
- Inflammatory joint dz
–> Infx (often viral)
–> Reactive arthritis
–> Psoriatic arthritis
–> RA
–> Crystal-induced
–> Systemic rheumatic illness**
–> Other systemic illness or malignancy (IBD)
–> Juvenile idiopathic arthritis
What bacterial infx can causes polyarticular w/ synovitis?
- Lyme Dz
- Gonococcal
- Staph
What viral infx can causes polyarticular w/ synovitis?
- Hep B or C
- Parvovirus
- Dengue virus
- Alphaviruses (chikungunya, equine encephalitis),
- HIV
- Mumps
- CMV
List rheumatic illnesses that can cause polyarticular w/ synovitis.
- lupus
- vasculitis
- systemic sclerosis
- polymyositis
- dermatomyositis
Polyarticular w/o synovitis conditions
- Fibromyalgia
- OA
- Neuropathic pain
- Depression
- Metabolic bone dz
- Endocrine disorder – hypothyroid, hyperparathyroid
- Plasma cell myeloma
Workup for Monoarticular
- Imaging
- Arthrocentesis w/ analysis
- Labs (if needed)
- Synovial biopsy (RARE)
Do you usually order imaging for monoarticular?
YES
we tend to get imaging when one joint is involved
When would you want an arthrocentesis w/ synovial fluid analysis?
diagnose septic arthritis or gout
Labs for Hemarthrosis w/o trauma
PT/INR, PTT, CBC
(checking for coag disorders like hemophilia)
Labs for evidence of joint inflammation w/o infx (septic) or crystals
- ESR/CRP, CBC, CMP
- Testing for systemic rheumatic dz IF suspicion of that dz
- Testing for Lyme dz IF suspicion is high
When would you do synovial biopsy?
- Fungal infx
- Sarcoidosis
- Lymphoma of the synovial joint
Workup for polyarticular w/ synovitis (red swollen joint)
- CBC, CMP, UA (uric acid crystals, Ca++ crystals)
- Arthrocentesis w/ synovial fluid analysis
- Labs based on clinical suspicion
–> ESR/CRP
–> Suspected systemic illness (RA, Lupus, Other systemic dz (IBD))
–> Viral antibodies (Hep B, C, Parvovirus B19)
–> Imaging – rarely needed - Synovial biopsy - rare
Workup for Polyarticular w/o synovitis
- CMP
- TSH / PTH
- Imaging – x-ray
- Screening for depression
Arthrocentesis w/ Synovial Fluid Analysis Indications
- joint effusion/pain - dx of underlying pathology
- therapeutic
Arthrocentesis w/ Synovial Fluid Analysis Indications: example of underlying pathology
- Infx (Septic arthritis)
- Arthritis
- Crystalline arthritis (gout, pseudogout)
- Synovitis (inflammation)
- Neoplasm
Arthrocentesis w/ Synovial Fluid Analysis Indications: therapeutic
Injection of anti-inflammatory meds into the joint
What does a synovial fluid analysis include?
- Color & clarity
- Viscosity
These are ordered separately & must tell the lab
- Gram stain & culture
- Cell count & differential
- Crystal analysis
- Cytology
Synovial Fluid Analysis: NORMAL
Clarity:
Color:
Viscosity:
WBC/mm3:
PMNs% (neutrophils):
Clarity: Transparent
Color: Clear
Viscosity: High
WBC/mm3: < 200
PMNs% (neutrophils): < 25%
Synovial Fluid Analysis: Non-inflammatory
Clarity:
Color:
Viscosity:
WBC:
PMNs% (neutrophils):
Clarity: Translucent
Color: Yellow
Viscosity: High
WBC: 200 - 2,000
PMNs% (neutrophils): <25%
Synovial Fluid Analysis: Inflammatory
Clarity:
Color:
Viscosity:
WBC:
PMNs% (neutrophils):
Clarity: Translucent
Color: Yellow
Viscosity: Low
WBC: 2000 - 10,000 (up to 100,000)
PMNs% (neutrophils): >50%
Synovial Fluid Analysis: Septic
Clarity:
Color:
Viscosity:
WBC:
PMNs% (neutrophils):
Clarity: Opaque
Color: Dirty Yellow
Viscosity: Variable
WBC: >80,000
PMNs% (neutrophils): >75%
Synovial Fluid Analysis: Hemorrhagic
Clarity:
Color:
Viscosity:
WBC:
PMNs% (neutrophils):
Clarity: Bloody
Color: Red
Viscosity: Variable
WBC: 200 - 2,000
PMNs% (neutrophils): 50 - 75%
Arthrocentesis w/ Synovial Fluid Analysis Contraindications
- Artificial joint/joint replacement
- Lesions of skin overlying injection site
What is gout?
a build up uric acids crystals in the joint space
(very painful during gout attack)
Describe Tophaceous gout
pt has gout–> develop nodules called tophi–> can cause ulcerations (can occur anywhere on the body)
Gout testing:
- Have to distinguish from septic (infected) joint
- Crystal analysis of synovial fluid
monosodium urate crystals (look like needles)
–> “yellow” – negatively birefringent - Uric acid level
–> Hyperuricemia can cause crystalline arthropathy
–> Not sensitive or specific
–> Can be low/normal during a gout attack
Immediate Tx for Gout
Prednisone 1st line
NSAID (indomethacin) 2nd line
Pain meds
Colchicine 4th line
Prevention of Gout Meds
- Allopurinol
- Probenecid
- Colchicine
What does CPPD stand for?
Calcium Pyrophosphate Dihydrate Deposition
CPPD is also known as…
pseudogout
Testing for CPPD diagnosis
- Crystal analysis of synovial fluid
–> CPPD crystals (square – rectangular)
—-> “Blue” – positively birefringent - Chondrocalcinosis on imaging
–> Calcium deposits in cartilage
What is a physiological sign that can be seen & is indicative of RA?
Ulnar deviation of the fingers
What meds can help prevent ulnar deviation in RA?
DMARDs
Lab Diagnostics for RA
- ESR/CRP
- Rheumatoid factor (RF)
- Anti-citrullinated peptide antibodies (ACPA)
What will be seen on imaging in RA
joint erosions & deformities (seen in longstanding RA)
Indications to order an RF factor
Patients with clinical symptoms consistent with RA
Classic symptoms that make you think RA
Symmetrical joint pain, inflammation, fingers & knees, hurts more in the morning & better w/ movement
Is the RF a screening test?
NO
RF Explanation
- IgM Ab are made against the constant region of IgG Ab (antibodies attacking antibodies)
- Associated w/ RA, but non-specific –> (+) in other conditions (i.e., SLE, scleroderma)
~ 70-80% of pts w/ RA will be RF+
–> Some pts may become RF+ at later date
Is RF specific or non-specific?
non-specific
What are the two Anti-citrullinated Peptide Abs (ACPA)?
- Anticyclic-citrullinated Ab (anti-CCP)
- Anti-mutated citrullinated vimentin Ab (anti-MCV)
What is Citrulline?
an amino acid
How does Citrulline form?
it is a derivative of arginine; post-translation modification
Are the Anti-citrullinated Peptide Abs (ACPA) specific or non-specific?
More specific for RA
How is Anti-citrullinated Peptide Abs (ACPA) used in relation to RA?
biomarker for dz progression
How do you diagnose RA?
- Clinical Dx
- Scoring system used (labs are one component)
- (+) RF & (+) ACPA highly specific for RA
- Also need to rule out other systemic rheumatologic dz like SLE
What PE findings are consistent w/ psoriasis?
Pitting of nails, silvery plaques that bleed
Labs for Psoriatic arthritis
- No definitive labs
- Lab testing mostly done to rule out other arthritises
- Some assoc. w/ HLA-B27 genotype
–> HLA = human leukocyte antigen
Psoriatic arthritis imaging changes
- “pencil-in-cup”
–> aka “Symmetric bone erosions of the margin” - Joint ankylosis (fusing) & joint destruction
Diagnostics for JIA
- Clinical dx
–> Childhood (average age 7yo)
How will a child present w/ suspected JIA?
Recurrent daily fever & polyarthritis
Expected Labs for JIA if done
- RF (-), ACPA (-)
- Elevated WBC & platelet counts
- Elevated ESR / CRP
- Very elevated ferritin
Most time it will go away after a few years
Prognosis of JIA
Most time it will go away after a few years
What is reactive arthritis?
- Arthropathy associated w/ other dz/disorders
–> GI infx, UTI, STI
Reactive arthritis Triad: Reiter’s syndrome
- urethritis (dysuria)
- arthritis
- conjunctivitis (red eyes)
When does reactive arthritis usually occur?
1-4 weeks after triggering infx
Reactive arthritis workup
- Clinical dx
- Rarely will have evidence of current infx
- (+/-) elevated ESR/CRP
- Arthrocentesis, if done = inflammatory synovitis
- Tx: Steroids
How does lupus manifest throughout the body?
It is multi-system
Describe the various effects of Lupus on each system.
Skin
- Rash worse w/ sunshine
- Butterfly rash
- Spares nasolabial folds
MSK
- Arthritis
Bone marrow
Renal
- Lupus Nephritis
Cardiac/Pulm
- Pericarditis
- Chest pain better when leaning fwd
- Pericardial friction rub
- Diffuse ST seg elevation
SLE Testing
Testing for autoantibodies
- Anti-nuclear antibodies (ANA) – initial test
- Anti-double stranded DNA Ab
- Anti-Smith (anti-extractable nuclear antigen) Ab
- Anti-chromatin Ab
- Anti-phospholipid Ab (cardiolipin, lupus anticoagulant, beta-2-glycoprotein)
–> Anti-phospholipid syndrome (prone to clotting; need lifelong anticoag)
Anti-nuclear Antibodies pathophys
Many autoimmune rheumatologic diseases have autoantibodies against nucleic acid (DNA/RNA) antigens == anti-nuclear antibodies
Is Anti-nuclear antibodies (ANA) specific for any one dz?
NO
Explain ANA testing
Test = titer (dilutional conc)
Initial test is a specific dilution, usually (1:40).
- If (+), serial dilution is done until no longer p(+).
–> Highest dilution that is still (+) is reported
- Higher numbers = higher dz activity
- Test is done using indirect immunofluorescence
–> Pattern of fluorescence can help differentiate b/t diseases, but less specific
ANA Interpretation
- (-) ANA helps to rule out SLE (high sensitivity)
- Can be (+) in ppl w/o autoimmune disorder (~5% of adults) (low specificity)
- Not used for screening
- Once (+), will usually remain (+)
Anti-double stranded DNA Antibody Indications
Dx & follow-up of help support SLE
Anti-double stranded DNA Antibody Explanation
- High titers assoc. with SLE
- Low titers can be found in other dz (hep C)
- Levels change w/ dz activity
–> Monitor treatment
—> Diagnose flares
Anti-extractable Nuclear Antigen (Anti-Smith & anti-RNP) Indicaitons
dx of SLE & mixed CT dz (MCTD)
Anti-extractable Nuclear Antigen (Anti-Smith & anti-RNP) Explanation
Most common anti-ENA Ab are anti-Smith (SM) & anti-ribonucleoprotein (RNP)
- Anti-SM Ab is present in SLE & MCTD.
–> Present only 30% in SLE, 8% in MCTD.
- Anti-RNP present in 99%+ pts w/ MCTD
If I suspect a pt to have SLE, which Anti-extractable Nuclear Antigen would I order?
Anti-SM Ab
If I suspect a pt to have MCTD, which Anti-extractable Nuclear Antigen would I order?
Anti-RNP
Anti-Ro/SSA is primarily found in…
Sjogren’s syndrome
Anti-La/SSB is usually positive in….
Sjogren’s syndrome
When can Anti-Ro/SSA be positive?
- rare cases of ANA-negative SLE
–> Anti-La/SSB negative in SLE
Antichromatin Antibody indications
Important marker in renal dz in SLE
Antichromatin Antibody explanation
Levels show direct correlation w/ renal damage assoc. w/ SLE
Prognosis of renal damage
Anti-histone antibody indications
- Important marker in drug-induced lupus erythematosus
- Drug-induced SLE –> usually (-) for anti-double stranded DNA antibodies
Common meds related to anti-histone antibody
- isoniazid
- Hydralazine
- Procainamide
- Minocycline
- TNF blockers
- Anti-seizure meds
- Methyldopa
- Sulfasalazine
Why is Anti-phospholipid syndrome and SLE important?
If (+), it predisposes to unprovoked arterial/venous clot formation
Test all SLE patients for…
anti-phospholipid syndrome
What are the 3 things we look for in Anti-phospholipid syndrome.
- Anti-cardiolipin Ab
- anti-beta 2 glycoprotein
- lupus anticoagulant
only 1 (+) means (+) for syndrome
Sjögren’s Syndrome dz process:
- lymphocytic infiltration of the exocrine glands (salivary & lacrimal (tears))
Results in dry mouth (xerostomia) & dry eyes (keratoconjunctivitis sicca).
Two type of Sjögren’s Syndrome
Primary & secondary
Testing for Sjögren’s Syndrome
- Labs
- Schirmer Test
- Sialometry
- salivary gland biopsy
Describe the labs for Sjogren’s Syndrome
- Anti-SS-A (anti-Ro) & Anti-SS-B (anti-La) are (+) in about 50% pts w/ primary Sjögren’s
- Can help to separate primary from secondary Sjogren’s
- Often ANA+ (>1:320) & RF+
- Elevated ESR/CRP
- CBC – anemia of Chronic Dz, leukopenia
- Low iron, high ferritin
- CMP – elevated PRO (polyclonal gammopathy)
–> A lot of different ab that are elevated
Describe Schirmer test
- Normal 15 mm in 5 mins
- Sjogren’s = 5mm
What is the most diagnostic test for Sjogren’s Syndrome?
Salivary gland biopsy
Categories of Systemic sclerosis (Scleroderma)
- Limited systemic sclerosis (CREST syndrome)
- Diffuse systemic sclerosis
- Systemic sclerosis sine scleroderma
Describe diffuse systemic Sclerosis
- Xerostomia (Dry)
- interstitial lung dz
- pulm HTN
- Barrett’s esophagus
- gastroparesis
- joint contractures
- uclers
- Raynaud’s
Basically a lot of fibrosis going on
Diffuse systemic sclerosis Testing
- ANA+ in 90-95%
- Anti-topoisomerase I (anti-Scl-70) Ab
- Anti-U3 RNP (fibrillarin) Ab
- anti-RNA polymerase Ab
What is the antibody of choice to test in diffuse systemic sclerosis?
Anti-topoisomerase I (anti-Scl-70) Ab
What is the antibody is correlated w/ dz severity in diffuse systemic sclerosis?
anti-RNA polymerase Ab
What does CREST syndrome stand for?
- Calcinosis
- Raynaud phenomenon
- esophageal dysmotility
- Sclerodactyly
- Telangiectasia
Describe Calcinosis Cutis
Calcium deposits under the skin (everywhere)
can look like tophaceous gout but diffuse
What can you order to differentiate calcinosis cutis from tophaceous gout?
uric acid level
What is Raynaud Phenomenon?
When you go out in the cold something turns white, blue, red or mixed
Describe esophageal dysmotility
Dysfunction of the esophagus leading to dysphagia, heartburn, choking
Describe Sclerodactyly
- Resorption of the distal phalanx
- Swelling of fingers (sausage fingers), skin is shiny, contractures, loss distal joint
Describe telangiectasias
enlarged capillaries under the skin
“spider veins”
Testing for SSc (CREST)
- ANA+
- Anticentromere Ab
MCTD is most common in…
- women
- teenagers to 20s
MCTD S/S:
- Overlapping features of Sjogren’s, SLE, Systemic sclerosis (maybe GI problems), polymyositis
- Raynaud syndrome, diffuse hand swelling, polyarthralgias, lung dz (ILD, pulm HTN)
MCTD Testing
- ANA+
- U1 RNP+ (99%)
- RF+; anti-Sm & anti-dsDNA (-)
What is happening in Ankylosing spondylitis?
Calcification of ligaments & joints
Ankylosing Spondylitis S/S
stiffness & pain
Ankylosing spondylitis Testing
Imaging
- Fusion of SI joint, “bamboo spine”
Labs
- HLA-B27 testing
- (when patients has clinical picture but no proof on imaging)
What is polymyositis?
- autoimmune inflammation of skeletal muscle tissue
–> progressive proximal muscle weakness
What is dermatomyositis?
- muscle weakness plus skin involvement
–> can be due to occult malignancy & poss. interstitial lung dz
Which cancers should you check for in women w/ dermatomyositis?
breast uterine, cervical & GI cancers
Which cancers should you check for in men w/ dermatomyositis?
Prostate & GI cancer
Polymyositis hits which joints?
shoulders & hips
Testing for Myositis
- Anti-Jo-1 (antihistidyl transfer synthase) Ab
- CPK (creatine kinase)
–> Elevated w/ inflammation or destruction of muscle cells - Aldolase
–> Alt to CPK, often tested when CPK is (-) - ESR/CRP – usually not elevated
Where does creatine kinase found?
found inside muscles
How is Polymyalgia rheumatica usually diagnosed?
largely a clinical dx
- proximal joint pain/stiffness
Testing for Polymyalgia rheumatica
- Elevated ESR/CRP
- Assoc. w/ HLA-DR4
- EMG
- MRI – muscle edema
- Muscle biopsy (definitive)
What is the definitive diagnostic test for polymyalgia rheumatica?
muscle biopsy
Polymyalgia rheumatica is often associated with…
giant cell arteritis (vasculitis)
(30-35%)
Is fibromyalgia inflammatory or non-inflammatory?
Non-inflammatory
Testing for fibromyalgia
- Clinical dx
- Rule out other dz
–> Hep C
–> Thyroid disorders
–> ESR/CRP
–> CBC
–> Only order testing for rheumatic dz if hx/PE or lab findings suggest it
What are Vasculitides?
Inflammation of BVs
List multiple types of Vasculitides
- Large vessels – Takayasu arteritis, giant cell arteritis
- Medium vessels – Polyarteritis nodosa, Kawasaki dz (peds)
Small vessels – ANCA-assoc. (polyangiitis), Immune complex (IgA, cryoglobulins)
Vasculitides labs is largely based on…
ruling out other dz
Labs to order for Vasculitides
- CBC, CMP, ESR/CRP
- Hepatitis panel (Hep B)
- Blood cultures
- decr complement levels
- ANA
How are Vasculitides definitely diagnosed?
Tissue biopsy or angiography
Giant cell arteritis affects…
large vessels
- aorta, carotids, extracranial branches
Who do we see giant cell arteritis in?
those >50 yo
Giant cell arteritis is assoc. w/…
polymyalgia rheumatica
Testing for giant cell arteritis
- Elevated ESR/CRP – usually very high
- Artery biopsy (often temporal artery)
Describe polyarteritis nodosa (PAN)
Rare, necrotizing vasculitis of medium-sized arteries
List medium-sized arteries affected by polyarteritis nodosa (PAN)
- Kidneys (not glomeruli)
- skin,
- joints
- muscles
- GI tract
Polyarteritis nodosa (PAN) is associated with…
Hep B & C
Polyarteritis nodosa (PAN) is seen in what population
Middle-aged adults
Polyarteritis nodosa (PAN) S/S
- systemic (fever, fatigue, etc)
- arthralgias & myalgias
- asymmetric sensory & motor issues in same area (multiple mononeuropathy)
- abd pain
- rapidly worsening HTN
- skin ulcers
Testing for Polyarteritis nodosa (PAN)
- Biopsy (focal)
- Hep B & Hep C
What is Granulomatosis w/ polyangiitis?
- Old name = Wegener’s granulomatosis
- Necrotizing vasculitis of small/medium vessels w/ granuloma formation
Granulomatosis w/ polyangiitis S/S
- Systemic sx
- Respiratory sx – upper (nosebleeds) & lower (hemoptysis)
- EENT sx (nasal congestion)
- Myalgias & arthralgias
- GN & AKI
- Multiple mononeuropathy
Testing for Granulomatosis w/ polyangiitis
- ESR/CRP
- UA (PROs & RBCs)
- CMP
- c-ANCA & p-ANCA — will be c-ANCA (+) to proteinase-3
- Imaging (CT chest) - shows granulomas
- Biopsies
What is Eosinophilic granulomatosis with polyangiitis?
- Old name = Churg-Strauss syndrome
- Necrotizing vasculitis of small vessels w/ eosinophilic granulomas
Eosinophilic granulomatosis w/ polyangiitis S/S
- Adult onset asthma / allergies
- Systemic sx
- Skin – extensor surface nodules
- Nerve – multiple mononeuropathy
- MSK – arthralgias/myalgias
- Heart – HF/myocarditis
Testing for Eosinophilic granulomatosis w/ polyangiitis
- CBC – eosinophilia
- ANCA – p-ANCA (+) for myeloperoxidase
- ESR/CRP
- Echo
- Biopsy
What is Microscopic polyangiitis?
Necrotizing vasculitis of small vessels WITHOUT granulomas
Microscopic polyangiitis S/S
- Systemic sx
- GN & AKI
- Resp sx – lower (hemoptysis)
- Myalgias & arthralgias
Testing for Microscopic polyangiitis
- ANCA – p-ANCA (+) for myeloperoxidase
- ESR/CRP
- Imaging (CT chest)
- Biopsy