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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 – – – – – – – – 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 – Rash In 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 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) • • • • • • • 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 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 (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 [email protected] THANK YOU