1. Rheumatology Panel for Primary Care
Dr. Vu Kiet Tran, MD

2. 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

3. Disclosure Medical advisor Medical director Dynacare laboratories
Best Doctors Canada

4. 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

5. What will you do and what tests would you order (if any)?
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)?

6. 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?

7. 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

8. Major causes of Inflammatory Polyarthritis
Etiologies
Infectious arthritis
Bacterial
Lyme
Bacterial endocarditis
Viral
Reactive Arthritis
Rheumatic fever
Reactive arthritis
Enteric infection
Rheumatoid Arthritis
Inflammatory Osteoarthritis
Crystal-induced arthritis
Etiologies
Systemic rheumatic illnesses
SLE
Vasculitis
Systemic Sclerosis
Polymyositis/dermatomyositis
Still’s disease
Behcet’s disease
Relapsing polychondritis
Seronegative Spondyloarthritis
Ankylosing spondylitis
Psoriatic arthritis
IBD
Systemic illnesses
Sarcoidosis
Palindromic rheumatism
Familial Mediterranean fever
Malignancy
Hyperlipoproteinemias

9. History Presence of arthritis (synovitis) or not Mono or polyarthritis
Seek out join emergencies
Fever
Hot and swollen joints
Weight loss/malaise

10. History Joint symptoms Pain quality Time of onset Duration
Exacerbating or relieving factors

11. Joint symptoms Inflammatory Non-inflammatory
Pain is worsened with immobility
Morning stiffness or “gelling”
Joint involvement is usually symmetrical
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

12. Associated symptoms Non-rheumatic Rheumatic
Weakness (neurologic or myopathic illnesses)
Fever
Night sweats
Weight loss
Multi-system involvement
Fatigue
Rash
Adenopathy
Alopecia
Oral or nasal ulcers
Pleuretic chest pain
Raynaud’s phenomenon
Dry eyes or mouth
1. Presence of extra-articular symptoms help narrow the Ddx.

13. History Focus on Usual areas PMHx Medication list Family history
Social history
ROS
History of joint injury
Functional capacity
Psychological state and social support

14. Physical exam Establish the presence of synovitis Axial involvement
Soft tissue swelling
Warmth over the joint
Joint effusion
Loss of motion
Axial involvement
Seronegative spondyloarthritis

16. Physical exam Subcutaneous nodules (rheumatoid nodules vs tophi)
Skin lesions
Eye manifestations
Keratoconjunctivitis sicca
Uveitis
Conjunctivitis
Episcleritis

20. Classification Criteria

21. Adding radiographs

22. 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”

23. SLE
Diagnosis is based on clinical judgment, after excluding other diagnoses
Heterogeneity (broad range) of clinical presentation is often a challenge

24. SLE
Classic triad
Fever
Joint pain
Rash
In women of child-bearing age

25. Symptoms of Lupus Constitutional symptoms Photosensitivity
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

27. Laboratory studies Not always necessary to make a diagnosis
Can sometimes be misleading

28. Laboratory studies ESR CRP ANA Rheumatoid factor (RF)
Anti-citrullinated peptides (Anti-CCP)
Uric acid
Antibodies
Strept A
Hep B
Hep C
Borrelia Burgdorferi (Lyme)

29. ESR Non-specific marker of inflammation Never diagnostic
May be abnormal in
Advancing age
Gender
Infectious, malignant, rheumatic diseases
Renal failure
Diabetes
obesity
Occult malignancy
May be normal in up to 70% of RA patients

30. 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 hours
normalize within a week
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

31. 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

32. ANA
The higher the ANA titer, the more likely that the patient has either SLE or another ANA-associated disease
ANA is positive in all SLE patients at some time in the disease

33. Diseases associated with positive ANA

34. Rheumatoid Arthritis Panel
Rheumatoid factor
Anti-CCP (anti-cyclic citrullinated peptide)
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
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

36. SLE specific antibodies
Anti-DsDNA
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)

37. SLE specific antibodies
Anti-SSA (Ro)
Anti-histone
VDRL
C3, C4, CH50 complements
ENA (Extracted Nuclear Antigen) antibodies
Anti-RNP
Anti-Sm
Anti-SSB (La)
Scl-70
Anti-Jo-1
Urine protein-to-creat ratio

38. Systemic Scleroderma panel
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

39. Sjogren’s Syndrome panel
Anti-SSA (Ro)
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

40. 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

41. Mixed Connective Tissue Disease Panel
Anti-U1 RNP
Highly associated with MCTD
Positive in % of MCTD patients
May also be positive in SLE and Scleroderma

42. 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 (p-ANCA)
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

45. Imaging Plain radiographs RA Ankylosing Spondylitis
Erosion at wrist, hand, foot
Ankylosing Spondylitis
Calcium pyrophosphate crystal deposition disease (CPPD)
chondrocalcinosis

46. Imaging
Ultrasound
Tendonitis
Bursitis

47. Joint aspiration

48. summary

51. 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

52.
Thank you