1 / 32

Laboratory Testing in Rheumatology: Take the High Value Road

Laboratory Testing in Rheumatology: Take the High Value Road. William E Davis, MD, FACP. Markers of inflammation ESR CRP Rheumatoid factor and anti-CCP antibodies Anti-nuclear antibodies. Inflammation. Transcription factors Signal transducer and activator of transcription 3 (STAT3)

armand
Download Presentation

Laboratory Testing in Rheumatology: Take the High Value Road

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Laboratory Testing in Rheumatology: Take the High Value Road William E Davis, MD, FACP

  2. Markers of inflammation • ESR • CRP • Rheumatoid factor and anti-CCP antibodies • Anti-nuclear antibodies

  3. Inflammation • Transcription factors • Signal transducer and activator of transcription 3 (STAT3) • Janus activated kinase (JAK) • Nuclear factor κB • Acute phase response • Cytokine production • Hepatic plasma proteins ↑ 25% • CRP • SAA • Complement • Ceruloplasmin • Haptoglobin • Fibrinogen • Negative acute phase proteins • albumin, prealbumin, transferrin

  4. Edmund Biernacki • Robert SannoFåhræus

  5. ESR: Erythrocyte Sedimentation Rate • Electrostatic charges prevent rouleaux formation and sedimentation • Plasma proteins and fibrinogen ↑ • Microcytosis, polycythemia ↓ • Pregnancy, ESRD ↑ • Normal M <15mm, F < 20 mm • Elderly M = age/2 • Elderly F = age/2+10

  6. ESR: Advantages • Simple • Inexpensive • Strong evidence base

  7. C-Reactive Protein • Binds C-polysaccharide of streptococcus • Normal <1mg/dL (<10mg/L) • Binds apoptotic cells, Fcγ receptors, activates complement • >1000 fold increase in acute phase • Peak 2-3 days • T ½ = 19h • Persistently elevated in RA, tuberculosis, malignancy • > 15 mg/dL in bacterial infection

  8. CRP • Advantages • Modest cost • Automated nephelometry • Serum test • Evidence data base solid • Limitations • Obese, elderly, ethnicity

  9. 75 y/o caucasian male presents with new onset temporal headache x 2 weeks. • PMH: HTN, on ACE inhibitor • Normal vital signs and physical examination • ESR/CRP?

  10. 47 y/o female with 10 year hx rheumatoid arthritis, on MTX and tnf-inhibitor (etanercept), presents with hx acute shaking chill, cough with brick red sputum, fever, physical examination and CXR c/w RML pneumonia • ESR/CRP?

  11. Utility of ESR / CRP • Evaluate the extent or severity of inflammation • Monitor disease activity over time and with treatment • Assess prognosis

  12. Rheumatoid Factor • Sheep cell agglutination test • IgM antibodies that recognize Fc of IgG • Normal: <15 I.U./L • 1% young healthy, up to 5% elderly • Present in RA, Sjogren’s syndrome, HCV-cryoglobulinemia • Prognostic Υ Υ Υ Υ Υ Υ Υ

  13. Anti-Cyclic Citrullinated Peptide (CCP) Antibodies • Anti-perinuclear factor (APF) • Anti-keratin antibodies (AKA) • Citrullinatedfilaggrin • Cyclic citrullinated peptide (CCP)

  14. Anti-CCP • Sensitivity 82.9% • Specificity 93-94% • Predicts development of RA in early arthritis • Associated with severe, destructive disease • Radiographic progression • Total joint prosthesis • Disability • May precede development of RA by years • 30-60% CCP+ up to 6 years before dx

  15. RF and Anti-CCP • 48 y/o male with symmetric polyarthralgia progressive x 3-4 years • Hx HTN • PE: No joint swelling or deformity • Lab: normal CBC, mild increase AST, ALT <2x normal • RF + 55 IU • CCP negative • ?

  16. RF and Anti-CCP • 48 y/o male with symmetric polyarthralgia progressive x 3-4 years • Hx HTN • PE: No joint swelling or deformity • Lab: normal CBC, mild increase AST, ALT <2x normal • RF + 55 IU • CCP negative • HCV – chronic HCV associated with RF and arthralgia

  17. RF and Anti-CCP • 32 y/o female with symmetric polyarthralgia for 6 weeks; sx controlled with NSAID • PMHx: negative except G2P2 • PE: Slight joint swelling and tenderness MCP’s, wrists, ankles & MTP’s • Lab: normal CBC, CMP, slightly elevated ESR 30, CRP 2 mg/dL • RF + 55 IU • CCP >100 U/ml • ?

  18. Anti-nuclear antibodies • 1948 LE Cell • 1957 FANA test Υ Υ Υ Υ Υ Υ FITC Υ Υ Υ Υ Υ Υ

  19. Anti-nuclear antibodies • Chromatin associated antigens • DNA (dsDNA, ssDNA) • Histone • Kinetochore (centromere) • Ribonucleoproteins (snRNP) • Sm • U1 RNP • Anti-Ro/SSA and Anti-La/SSB • Ribosomal P protein • Nucleolar antigens • Kenetochore • Topoisomerase • RNA polymerase • PM-Scl-75 and PM-Scl-100 components of exoribonuclease • Aminoacyl-tRNAsythetases (Jo-1)

  20. Fluorescent ANA test • Technician reads pattern and titer • Expensive • Subjective (1:160 or 1:320?) • Substrate • Rodent liver or kidney • Human cultured cell lines, e.g. Hep-2 • ELISA for specific antigen specificity • +ANA → ELISA testing

  21. Coat beads or microtiter plates with multiple antigens • Incubate patient plasma; measure reactivity • Any reactivity - positive -SSA/Ro SSB/La- -dsDNA RNP- -Sm Histone-

  22. Systemic Lupus Erythematosus • 31 y/o female presents with pericarditis • She reports intermittent joint swelling and pain, photosensitive dermatitis • WBC 3500, platelets 110,000 • ANA 95% sensitive • Anti-Sm specific • Anti-dsDNA specific and high levels predict renal disease

  23. Drug induced SLE • 65 y/o F presents with several weeks inflammatory arthritis of hands. • PMH: HTN, CHF, multiple med’s • PE: swollen MCP joints • Lab: normal except WBC 4000, Platelets 125,000 • ANA: 1:320, homogenous • Negative DNA, Sm, SSA/Ro, SSB/La • Rheumatologist Rx’s hydroxychloroquine • Internist discontinues hydralazine • Anti-histone antibody positive

  24. Sjogren’s Syndrome • 58 y/o female has symmetric joint swelling without deformity; she has dry eyes and dry mouth and swollen parotid glands • Lab normal except hypergammaglobulinemia • RF 150 IU • CCP negative • ANA 1:1280 • Anti-Sm, Anti-DNA neg • Anti-SSA, anti-SSB positive

  25. 32 y/o female complains of fatigue, dyspnea, joint pain, and Raynaud’s phenomenon x 6 months • PE normal except Raynaud’s • Lab normal except ANA + 1:1280, nucleolar • Anti-topoisomerase (Scl70): diffuse systemic sclerosis • Anti-centromere : CREST syndrome • Pulmonary vascular hypertension • Raynaud’s with negative ANA: 7% risk of rheumatic disease • Raynaud’s with positive ANA: 19-30% risk of rheumatic disease

  26. Inflammatory muscle disease • 62 yo male with joint pain, Raynaud’s, and symptoms of proximal muscle weakness • CPK 2000 • +ANA • 40-80% PM/DM patients have +ANA • Anti-Jo-1 associated with “anti-synthetase syndrome” and interstitial lung disease

  27. Overlap syndromes • Myositis • Raynaud’s, arthritis, puffy fingers • Lupus or scleroderma overlap • “MCTD” • Anti-RNP, Anti-PM-Scl

  28. Negative ANA: lupus unlikely • Positive ANA not helpful (%+): • Discoid lupus (5-25) • Fibromyalgia (15-25) • Rheumatoid arthritis (30-50) • Relatives of patients (5-25) • Multiple sclerosis (25) • Thyroid disease (30-50) • Silicone breast implants (15-25)

  29. Summary • Symptomatic patient with Positive ANA: look for specificity • Lupus: DNA and Sm specific • Anti-DNA prognostic and an activity marker • Histone may indicate drug induced • SSA, SSB correlate with neonatal damage • Sjogren’s syndrome: SSA, SSB • Systemic sclerosis (SSc): 97% +ANA • Centromere: limited sclerosis and pulmonary hypertension (CREST) • Topoisomerase/Scl70: diffuse disease with poor prognosis • Inflammatory myositis: 40-80% + ANA, most specifics negative • Anti-Jo-1 : poor prognosis and risk of pulmonary hypertension • RNP , PM-Scl : associated with overlap syndromes (SLE, SSc) • Raynaud’s: ANA useful for prognosis

  30. Summary • ESR/CRP • Identify extent or severity of inflammatory disease • Monitor disease activity (RA) • Assess prognosis in early arthritis • RF/CCP • Use anti-CCP test to improve the specificity for RA • +RF and +CCP predict worse prognosis • ANA • Very sensitive test for SLE but technically challenging • ANA specificities should be guided by clinical signs of autoimmune disease • Prevalence of ANA specificities may be very low

More Related