Download Rheumatology panel for Primary Care - CAPA

Rheumatology Panel for Primary
Care
Dr. Vu Kiet Tran, MD
Objectives
• Recognize history and physical exam are the
cornerstone of diagnosis for most
rheumatologic diseases
• Analyze rheumatology panels in conjunction
with history and physical exam to derive a
diganosis
• Enumerate the limitations of these
rheumatology panels
Disclosure
• Medical advisor
– Dynacare laboratories
• Medical director
– Best Doctors Canada
Case 1
• 56yo female with joint pain in both knees for
3-4 months.
• It is worse after a long day standing at work.
• She has a hard time going up and down stairs
• It is worsening
She wants testing for Rheumatoid arthritis
Case 2
• 36yo female presents with fatigue and
shortness of breath on exertion.
• She is losing hair and has a facial rash that
appeared 3 weeks ago.
• She is concerned she has Lupus like her
mother.
What will you do and what tests would you
order (if any)?
Case 3
• 37yo male sees you because her has been c/o
joint pains in the hand for 3-4 weeks
• He feels the joint are stiff in the morning
What other symptoms are you looking for?
Take Home Messages
• History and physical exam are the
fundamentals for an accurate diagnosis
• The lab tests are used to confirm or refute
your clinical impression
• Lab testing is not always necessary to make a
diagnosis
– Can sometimes be misleading
• High degree of false positives
– Lead to additional and unnecessary testing
Major causes of Inflammatory Polyarthritis
Etiologies
Etiologies
Infectious arthritis
Bacterial
Lyme
Bacterial endocarditis
Viral
Systemic rheumatic illnesses
SLE
Vasculitis
Systemic Sclerosis
Polymyositis/dermatomyositis
Still’s disease
Behcet’s disease
Relapsing polychondritis
Reactive Arthritis
Rheumatic fever
Reactive arthritis
Enteric infection
Rheumatoid Arthritis
Inflammatory Osteoarthritis
Crystal-induced arthritis
Seronegative Spondyloarthritis
Ankylosing spondylitis
Psoriatic arthritis
IBD
Systemic illnesses
Sarcoidosis
Palindromic rheumatism
Familial Mediterranean fever
Malignancy
Hyperlipoproteinemias
History
• Presence of arthritis (synovitis) or not
• Mono or polyarthritis
• Seek out join emergencies
– Fever
– Hot and swollen joints
– Weight loss/malaise
History
• Joint symptoms
– Pain quality
– Time of onset
– Duration
– Exacerbating or relieving factors
Joint symptoms
Inflammatory
• Pain is worsened with
immobility
• Morning stiffness or
“gelling”
• Joint involvement is usually
symmetrical
Non-inflammatory
• Pain is worsened by
mobility and weight-bearing
• Pain is relieved by rest
• Joint involvement in OA is
frequently asymmetrical,
especially in the larger
joints
Associated symptoms
Non-rheumatic
• Weakness (neurologic or
myopathic illnesses)
• Fever
• Night sweats
• Weight loss
Rheumatic
• Multi-system involvement
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Fatigue
Rash
Adenopathy
Alopecia
Oral or nasal ulcers
Pleuretic chest pain
Raynaud’s phenomenon
Dry eyes or mouth
History
• Focus on
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Usual areas
PMHx
Medication list
Family history
Social history
ROS
History of joint injury
Functional capacity
Psychological state and social support
Physical exam
• Establish the presence of synovitis
– Soft tissue swelling
– Warmth over the joint
– Joint effusion
– Loss of motion
• Axial involvement
– Seronegative spondyloarthritis
Physical exam
• Subcutaneous nodules (rheumatoid nodules
vs tophi)
• Skin lesions
• Eye manifestations
– Keratoconjunctivitis sicca
– Uveitis
– Conjunctivitis
– Episcleritis
Classification Criteria
Adding radiographs
Diagnosis of RA
• Classification criteria is not diagnostic criteria
• There is no diagnostic criteria for RA
• Classification criteria might be a guide to
“clinical diagnosis”
SLE
• Diagnosis is based on clinical judgment, after
excluding other diagnoses
• Heterogeneity (broad range) of clinical presentation
is often a challenge
SLE
• Classic triad
– Fever
– Joint pain
– Rash
In women of child-bearing age
Symptoms of Lupus
• Constitutional symptoms
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Fever
Weight loss
Fatigue
Lymphadenopathy
• Photosensitivity
– Malar rash
• Painless oral or nasal
ulcer
• Patchy hair loss
• Raynaud’s phenomenon
• Migratory/symmetrical
joint swelling
• Serositis
– Pleuretic chest pain or
dyspnea
• Pericarditis
– Pleuretic chest pain
• Leg edema
• Seizure/psychosis
Laboratory studies
• Not always necessary to make a diagnosis
• Can sometimes be misleading
Laboratory studies
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ESR
CRP
ANA
Rheumatoid factor (RF)
Anti-citrullinated peptides (Anti-CCP)
Uric acid
Antibodies
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Strept A
Hep B
Hep C
Borrelia Burgdorferi (Lyme)
ESR
• Non-specific marker of inflammation
• Never diagnostic
• May be abnormal in
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Advancing age
Gender
Infectious, malignant, rheumatic diseases
Renal failure
Diabetes
obesity
Occult malignancy
• May be normal in up to 70% of RA patients
CRP
• Synthesized in the liver in response to tissue injury
• Levels change more quickly than the ESR
– can increase within 4-6 hours
– peak at 24-72 hours
– normalize within a week
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•
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Non-specific marker of inflammation
Never diagnostic
It is more stable and less variable than ESR
More reliable for longitudinal
measurement/monitoring disease activity than RF
ANA
• High sensitivity for SLE
• Low specificity for SLE
• Therefore, a negative test essentially rules-out
SLE
• High false positives
– Up to 30% of healthy people may turn out to have a
positive titer
– Even in the presence of a positive ANA, a patient with
few or no clinical features of SLE is unlikely to have SLE
ANA
• The higher the ANA titer, the more likely that
the patient has either SLE or another ANAassociated disease
• ANA is positive in all SLE patients at some time
in the disease
Diseases associated with positive ANA
Rheumatoid Arthritis Panel
Rheumatoid factor
Anti-CCP (anti-cyclic citrullinated
peptide)
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Commonly used in the diagnosis of
RA
Positivity implies a more severe
course but is not specific
Sensitivity for RA varies (around 50%
– 80%)
Usually lower in early RA and higher
in established clinical disease.
Higher titers are associated with
more severe disease but fare poorly
as a longitudinal measure of disease
activity.
Measurement of RF isotypes have
been found to be clinically useful
–
IgA RF isotype has been linked to erosive
disease
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Sensitivity to RA is similar to that of RF
(50-85%)
More specific (90-95%)
Most useful in the setting of seronegative
subjects suspected of having RA
Detected in early RA & may even
antedate onset of inflammatory synovitis
Better predictor of erosive disease than RF
Does not correlate with extra-articular
disease
Positive anti-CCP + RF (IgM) correlates
strongly with radiographic progression
Not useful in longitudinal monitoring of
RA disease activity
SLE specific antibodies
• Anti-DsDNA
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high specificity for SLE
Often correlates with more active/severe disease
Positivity in SLE is also associated with renal disease or involvement
Tends to decrease or become undetectable in quiescent disease
• Anti-Sm
– Autoantibody with high specificity for SLE
– But only seen in 25-30% of SLE patients
– Unlike anti-ds DNA, it remains elevated even in quiescent disease
• Anticardiolipin antibodies
– Associated with an increased risk of vascular thrombosis, thrombocytopenia
and recurrent fetal loss in patients with SLE
– Also seen in Anti-Phospholipid Syndrome
• Lupus anticoagulant
– Immunoglobulin that binds with phospholipids that line cell membranes and
which usually prevents clotting in a test tube (in vitro)
SLE specific antibodies
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Anti-SSA (Ro)
Anti-histone
VDRL
C3, C4, CH50 complements
ENA (Extracted Nuclear Antigen) antibodies
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Anti-RNP
Anti-Sm
Anti-SSA (Ro)
Anti-SSB (La)
Scl-70
Anti-Jo-1
• Urine protein-to-creat ratio
Systemic Scleroderma panel
• Scl-70
– Positive in 20-60% of patients with diffuse Systemic Sclerosis
– Specificity is almost 100%
– Sensitivity is low
– When present, diagnosis of Scleroderma is almost certain
– Positivity is associated with an increased risk of radiographic
pulmonary fibrosis
• Anti-centromere
– Almost certainly rules in limited cutaneous Systemic Sclerosis/ CREST
– Indicates a high rate of pulmonary hypertension and primary biliary
sclerosis
• Anti-U3 RNP
– Its presence is associated with muscle, small bowel, renal and cardiac
involvement as well as pulmonary hypertension
Sjogren’s Syndrome panel
• Anti-SSA (Ro)
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Associated mainly with Sjogren’s Syndrome
Found in 75% of patients with primary Sjogren’s
Found in 10-15% of patients with secondary Sjogren’s
Found in 50% of patients with SLE (Subacute Cutaneous Lupus),
Cutaneous Vasculitis, Interstitial Lung Disease
– Also associated with other conditions such as Neonatal Lupus
Syndrome and congenital heart block
• Anti-SSB (La)
– Found in 40-60% of those with Sjogren’s Syndrome
– Rarely present without Anti-SSA (La)
– May also be positive in SLE (associated with ANA-negative
Lupus) and Scleroderma
Polymyositis/dermatomyositis panel
• Anti-jo-1
– Associated with Polymyositis/ Dermatomyositis and
Interstitial Lung Disease
– Presence typically implies severe muscle involvement and
resistance to treatment
• Anti-SRP
– Presence indicate patients who have
• severe, refractory disease
• those who may have cardiac involvement or cardiomyopathy
• CK
• Aldolase
• Anti-Mi2
Mixed Connective Tissue Disease Panel
• Anti-U1 RNP
– Highly associated with MCTD
– Positive in 95-100% of MCTD patients
– May also be positive in SLE and Scleroderma
Vasculitis Panel
• ANCA
• Used in the evaluation of vasculitis (i.e. Wegener’s granulomatosis,
microscopic polyarteritis, Churg-Strauss syndrome)
• Two target antigens are PR3 (proteinase-3) and MPO (myeloperoxidase)
• Two basic staining patterns are cytoplasmic (c-ANCA) and perinuclear (pANCA)
– some diseases have a predilection for one pattern.
• c-ANCA pattern is highly sensitive and is seen in more than 90% of
active Wegener’s granulomatosis wherein PR3 is the antigen
involved
• p-ANCA pattern is commonly associated with microscopic
polyarteritis and is directed against MPO
– The more active and extensive the vasculitis, the more likely are ANCA
assays to be positive
Imaging
Plain radiographs
• RA
– Erosion at wrist, hand, foot
• Ankylosing Spondylitis
• Calcium pyrophosphate crystal deposition
disease (CPPD)
– chondrocalcinosis
Imaging
Ultrasound
• Tendonitis
• Bursitis
Joint aspiration
SUMMARY
Take Home Messages
• History and physical exam are the
fundamentals for an accurate diagnosis
• The lab tests are used to confirm or refute
your clinical impression
• Lab testing is not always necessary to make a
diagnosis
– Can sometimes be misleading
• High degree of false positives
– Lead to additional and unnecessary testing
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THANK YOU