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

Infectious arthritisBacterial

LymeBacterial endocarditis

ViralReactive ArthritisRheumatic feverReactive arthritisEnteric infection

Rheumatoid Arthritis

Inflammatory Osteoarthritis

Crystal-induced arthritis

Etiologies

Systemic rheumatic illnessesSLE

VasculitisSystemic Sclerosis

Polymyositis/dermatomyositisStill’s disease

Behcet’s diseaseRelapsing polychondritis

Seronegative SpondyloarthritisAnkylosing spondylitis

Psoriatic arthritisIBD

Systemic illnessesSarcoidosis

Palindromic rheumatismFamilial Mediterranean fever

MalignancyHyperlipoproteinemias

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

– Fatigue– Rash– Adenopathy– Alopecia– Oral or nasal ulcers– Pleuretic chest pain– Raynaud’s phenomenon– Dry eyes or mouth

History

• Focus on – 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– RashIn women of child-bearing age

Symptoms of Lupus

• Constitutional symptoms– 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

• ESR• CRP• ANA• Rheumatoid factor (RF)• Anti-citrullinated peptides (Anti-CCP)• Uric acid• Antibodies

– Strept A– Hep B– Hep C– Borrelia Burgdorferi (Lyme)

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

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

• 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 ANA-associated disease

• ANA is positive in all SLE patients at some time in the disease

Diseases associated with positive ANA

Rheumatoid Arthritis Panel

Rheumatoid factor• 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

Anti-CCP (anti-cyclic citrullinated peptide)• 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

– 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• Anti-SSA (Ro)• Anti-histone• VDRL• C3, C4, CH50 complements• ENA (Extracted Nuclear Antigen) antibodies

– 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)– 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 (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

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

THANK YOUVukiet.tran@rogers.com