Infectious arthritis Bacterial Viral Other Postinfectious (reactive) arthritis Rheumatic fever Reactive arthritis Enteric infection Other seronegative spondyloarthritides Ankylosing spondylitis Psoriatic arthritis Inflammatory bowel disease Rheumatoid arthritis Inflammatory OA Crystal-induced arthritis Systemic rheumatic illnesses: SLE, vasculitis, SSc, PM/DM Other systemic illnesses: sarcoidosis, malignancy, subacute endocarditis Quinn et al. How do you diagnose rheumatoid arthritis early. Best Pract Res Clin Rheumatol 2001;15a:49-66

 In Rheumatoid arthritis and Psoriatic arthritis:  Radiographic damage within weeks of onset  Window of opportunity with early DMARD for possible “cure”  Both radiographic damage and disease activity are independent predictors disability  Polyarthritis may be 1 st indicatior of systemic illness (HIV, cancer, SLE)

2010 ACR/EULAR Classification Criteria for RA JOINT DISTRIBUTION (0-5) 1 large joint large joints1 1-3 small joints (large joints not counted) small joints (large joints not counted)3 >10 joints (at least one small joint) 5 SEROLOGY (0-3) Negative RF AND negative ACPA0 Low positive RF OR low positive ACPA2 High positive RF OR high positive ACPA3 SYMPTOM DURATION (0-1) <6 weeks0 ≥6 weeks1 ACUTE PHASE REACTANTS (0-1) Normal CRP AND normal ESR0 Abnormal CRP OR abnormal ESR1 ≥6 = definite RA What if the score is <6? Patient might fulfill the criteria…  Prospectively over time (cumulatively)  Retrospectively if data on all four domains have been adequately recorded in the past

 30-40% of patients presenting with synovitis will remain unclassified  As many as half will go into remission, and be off of medications in one year  About 1/3 will go onto to develop persistant synovitis, rheumatoid arthritis  Studies indicate that earlyDMARD use if started w/in critical window (<3months)may prevent progression to chronic arthritis

 Hydroxychloroquine  Sulfasalazine  Methotrexate  Leflunomide  Azathioprine  Gold  Minocycline  TNF inhibitors  Combination of above Based on multiple studies ≈ 30% of patients will achieve DAS28 of ≤ 3.2 on MTX monotherapy (1-3) 1.BeSt. 2 year data. Ann Int Med 2007; 146: Swefot. Lancet 2009; 374: TEAR. Arthritis Rheum 2009; 60:S707

 Patients with disease duration < 2years (mean duration 4 months)  Compared SSZ monotherapy with combination therapy of: Oral prednisone (60mg  7.5mg by 6 weeks  d/cd by week 28 MTX 15mg po (stopped at week 40) Sulfasalazine  Significant clinical improvement in combo group, but only while steroid on board  Less radiographic damage at week 56 with combination therapy  5 year follow up showed sustained suppression of the rate of radiographic progression, independent of subsequent treatment.

SulfasalazinePlus Methotrexate and HydroxychloroquineDose escalationOral prednisoneMethotrexate and CyclosporineOther DMARD 110 pts randomized, active RA < 5 years duration for 18 months. Two groups: usual therapy versus intensive therapy *Intra-articular steroid injections used but biologics were not. Grigor, Porter, Stirling, Capell. Lancet 2004:364:263-9

Intensive group n = 55 Routine group N = 55 Odds ration (95%) (p<0.001) EULAR good response 80%44%3.6 ( ) EULAR remission65%16%9.6 ( ) ACR 2089%64%4.0 ( ) ACR 5082%45%4.9 (2.1 – 11.4) ACR 7070%18%9.5 (3.9 – 23.0) Grigor et al. Lancet 2004: 364:263-69

MonoDoubleTripleI vs III vs IIIII vs III (P Values) ACR %73.5%87.9%<0.001 Remission31.5%44.6%60.3%0.007 No Xray progression 24.5%64.2%68.9% Calguneri et al. Clin Exp Rheumatology 1999:17: *ERA trial: 63% no radiographic progression at 2 years

Should we use combinations initially in all new patients or use a rapid step-up to combinations only in those that need it?  COBRA, FINRa-Co, Calguneri, PREMIER, all favor combinations initially.  TICORA shows that rapid step-up can be very effective, as does 2 year BeSt data and TEAR  TEAR shows no penalty for waiting (step up at 4-6 month mark)

 Studies out of the UK have shown a dramatic reduction in delays to rheumatologic evaluation  Studies in the 1980’s, found the median delay from symptom onset to referral was over 20 months, in one large teaching hospital in Glasgow, UK  Subsequent studies in the 90’s indicated that most of the delay stemmed from time to seek initial medial care (avg 4months) and time to seeing rheumatologist another month  In Austria, nation-wide public campaign advising people with signs of inflammatory arthritis to contact their GP

 Several studies suggest that the very early phase of disease may be pathologically distinct from established RA, which may represent a therapeutic window in which “cure” may be possible.  Rapid control of inflammation even in established RA with DMARD therapy has been shown to slow the progression of joint damage and disability.  Patients should be regularly followed to ensure “tight control” aiming for low disease activity or remission.