1. Value of inflammatory markers Useful for diagnosis of inflammatory vs non inflammatory conditions Remember NON-SPECIFIC, increased in infection, inflammation, malignancy Useful prognostically in RA Useful for monitoring therapy in PMR, TA, RA Main inflammatory markers used, ESR CRP –Other acute phase reactants ferritin

2. Pitfalls of ESR & CRP A normal result does not exclude inflammatory arthritis, eg small joints of hands, sacro-iliitis ESR changes slowly c/w CRP ESR increases with age, CRP does not –normal values men: age divided by 2 –Normal values women: age + 10 divided by 2 CRP more sensitive, wider range of abnormal values Discrepancies seen between ESR & CRP CRP  c/w ESR in infection

3. Active RA + septic arthritis

4. Autoimmune Serology Is an aid to clinical diagnosis Always requires clinical interpretation

5. Testing Philosophy (A) Sensitive screening tests RF, ANA, ANCA Expect many false positives (B) Specific confirmatory tests DNA, ENA, MPO, PR3 Expect some false negatives

6. DON’T RELY ON A POSITIVE TEST UNLESS THE CLINICAL PICTURE FITS

7. Rheumatoid Factor Positive in 75% RA (range 26 – 90%) –Negative RF dose not exclude diagnosis of RA Should order only if inflammatory joint symptoms or signs of RA Low specificity in general population (positive predictive value of less than 20%) False positives in 2-25% over 75 (Low titre) Present in infections eg SBE, Hep B,C Also in Sjogren’s, SLE Not used to monitor response to therapy

8. Antinuclear Antibody Generic term referring to antibodies with specificity for antigens in the cell nucleus

9. When to order an ANA? Aches and pains: When to do an ANA? This is a clinical decision eg NEW symptoms of inflammatory arthritis NEW symptoms of fatigue, other constitutional symptoms Intermittent fever

10. When to order an ANA arthritis mouth ulcers paraesthesia fever raynauds thrombocytopenia fatigue pleurisy thromboses rash anaemia miscarriages Alopecia sicca lymphopenia Clinical judgement, most of us fatigued at some time!

11. Importance of History Chronic left knee pain and + ANA = nothing New bilateral wrist pain and stiffness and ANA = suspicion of SLE

12. A.B. Female 42 Aches and pains everywhere 5 children who are mongrels Cries twice a day Demanding full time job Feel like leaving my husband No help from anyone Exhausted all the time GP ordered ANA + “NOW I’VE GOT LUPUS!”

13. M.C. Serology ANA positive titre 1:160 Fluorescent pattern Homogeneous

14. M.C. SEROLOGY Titres >160 often significant Presence of titre >1:640 increase suspicion of CT disease, presence alone NOT diagnostic, watch patient False + more common in women, elderly One study of 125 normal individuals –ANA >1:40 in 32%; >1:80 in 13%,; >1:320 in 3% If + ANA significant titre or clinical suspicion of SLE or Sjogren’s syndrome –do anti-DNA and anti-ENA as ANA too common and non-specific

15. Double stranded DNA antibodies a TRUE positive is rare unless SLE Only present in 50-60% of SLE Test results are NOT treated although relates roughly to disease activity

16. AUTOANTIBODIES TO EXTRACTABLE NUCLEAR ANTIGENS Ro/SSA, La/SSB, (U1) RNP, Sm, Jo-1, Scl-70 Rare in normals ‘pathogenic antibodies’ May be positive when ANA is negative (SSA), do if suspect SLE, Sjogren’s Disease specific and associated with particular clinical features

17. M.C. Serology dsDNA negative ENA negative Unlikely that she has lupus

18. Remember synovial fluid…..

19. Extra-articular features RA: nodules ~ 30%, vasculitis, pulmonary fibrosis, scleritis, sicca Psoriasis: skin rash Reactive arthritis: conjunctivitis, mouth/genital ulcers, urethritis Ankylosing spondylitis: uveitis SLE: pleuropericarditis, rashes, Raynaud’s etc Viral arthritis: rash, fever, systemic features

20. Summary HISTORY is critical to make diagnosis of Inflammatory arthritis –Prolonged early morning stiffness, swelling Inflammatory markers helpful, not diagnostic Xrays often normal early in disease Immunological tests helpful to categorise –Eg RA vs SLE vs scleroderma