From: Subject: Best Dx/Best Rx: Rheumatoid Arthritis Date: Wed, 3 Jun 2009 21:44:57 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0234_01C9E494.8A0D9B10" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0234_01C9E494.8A0D9B10 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx1502.htm Best Dx/Best Rx: Rheumatoid Arthritis



Rheumatoid = Arthritis=20

Gary S. Firestein, M.D.
University = of=20 California, San Diego, School of Medicine

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best = References

Definition=20

  • Chronic inflammation of the peripheral joints = of unknown=20 etiology

Key Clinical=20 Features

  • Acute or insidious onset, usually insidious = followed by=20 polyarticular involvement=20
  • 3/4 of patients are female=20
  • Onset may be preceded by major infection, = surgery,=20 trauma, childbirth, or other event=20
  • Small joints of hands and feet are usually = involved at=20 onset
  • Morning stiffness > 1 hr=20
  • Arthritis of > 3 joint areas (PIP, MCP, = wrist, elbow,=20 knee, ankle, MTP) for more than 6 weeks=20
  • Arthritis of > 3 hand joints=20
  • Symmetrical arthritis=20
  • Rheumatoid nodules=20
  • Serum rheumatoid factor=20
  • Radiographic changes (erosions or bony=20 decalcifications)
3D""bac= k to=20 top
Differential=20 Diagnosis=20
  • SLE=20
  • Polymyalgia rheumatica=20
  • Viral arthritis (e.g., parvovirus B19, = hepatitis B or=20 C)=20
  • Metabolic disorders (e.g., gout, calcium = pyrophosphate=20 deposition)=20
  • Septic arthritis=20
  • Seronegative spondyloarthropathies=20
  • Psoriatic arthritis=20
  • Osteoarthritis
3D""bac= k to=20 top
Best=20 Tests=20
  • Physical exam of joints=20
    • Swelling, warmth, tenderness, limited range = of=20 motion
  • X-ray=20
    • Often normal or shows juxtaarticular = osteopenia in=20 early cases=20
    • Useful for following disease = progression=20
    • Bone erosions at margins of the joint are = most=20 specific=20
    • Joint space narrows as articular cartilage = is lost=20
  • MRI=20
    • Can detect pannus invasion of joints=20
    • Best image for large joints =
  • No specific laboratory tests=20
  • Serology=20
    • Mild normochromic, normocytic anemia and = elevated=20 platelet count usually present; leukocyte count generally = normal=20
    • ESR and C-reactive protein level are usually = elevated=20 in active RA and are useful in monitoring disease activity and = response to=20 therapy=20
    • Serum chemistry usually normal=20
    • 80%=9685% of RA patients test positive for = rheumatoid=20 factor (RF), but specificity for RA is low and test may not be = positive=20 during first 6=969 mo=20
    • Antibodies to CCP more specific (85%=9690%) = but less=20 sensitive (50%=9660%) for RA than RF; could be a useful diagnostic = test in=20 some cases=20
    • Synovial fluid usually straw colored and = mildly=20 turbid; rarely diagnostic
3D""bac= k to=20 top
Best=20 Therapy=20


Drug Strategies=20

  • Consultation to confirm diagnosis and plan=20 treatment=20
  • Advance rapidly from NSAIDs to methotrexate = (and beyond,=20 if necessary) early, before joints are destroyed=20
  • Oral prednisone in low doses to control = symptoms until=20 disease-modifying antiarrhythmic drugs become effective=20
  • Rapidly increase methotrexate to 20=9625 = mg/wk=20
  • Methotrexate will not adequately control = symptoms in 70%=20 of patients; indications for advancing therapy:=20
    • Morning stiffness lasting > 30 min =
    • Continued pain=20
    • Evidence of active synovitis on physical = exam=20
    • Progressive erosion and deformities =
  • Combination therapy=20
    • Methotrexate + etanercept, infliximab, or = adalimu=20 mab=20
    • Methotrexate + sulfasalazine =B1=20 hydroxychloroquine=20
    • Methotrexate + leflunomide=20
    • Methotrexate + anakinra (usually reserved = for patients=20 who do not respond to methotrexate + TNF inhibitors) =
  • Prednisone is also used in patients requiring = adjunctive=20 "bridge" therapy between trials of single-drug or combination = therapies=20
  • Alternative management algorithms=20
    • Early triple therapy (e.g., sulfasalazine,=20 hydroxychloroquine, methotrexate)=20
    • Early high-dose corticosteroid therapy with = tapering=20 dose over several months, combined with methotrexate and = sulfasalazine;=20 patients improve rapidly due to steroid, but difficult to assess = efficacy of=20 second-line drugs=20
    • For recalcitrant cases, immunosuppressive = agents or=20 experimental approaches can be used

Drug Treatment for Rheumatoid = Arthritis

  • NSAIDs (response rate > 65%; onset of = action < 2=20 wk; toxicities: gastric erosion [nonselective inhibitors], renal = toxicity=20 [both selective and nonselective inhibitors]; relative efficacy = +)=20
    • Ibuprofen=20
      • Dose: 400=96800 mg t.i.d.=96q.i.d. =
    • Naproxen=20
      • Dose: 200=96500 mg b.i.d. =
  • Methotrexate (response rate > 70%; onset of = action=20 6=968 wk; toxicities: liver [fibrosis, elevated enzymes], hematologic, = oral=20 ulcers; relative efficacy +++)=20
    • Dose: begin at 7.5 mg once weekly, then = increase to 15=20 mg/wk over 2=963 mo if necessary; if no response, increase to = 20=9625=20 mg/wk=20
    • Cost/mo: $33
  • Leflunomide (response rate 50%; onset of = action 2=963 mo;=20 toxicities: GI, liver, skin rash, reversible hair loss; teratogen=97do = not use=20 in pregnancy; relative efficacy ++ to +++)=20
    • Dose: 20 mg/day=20
    • Cost/mo: $273
  • Hydroxychloroquine (response rate 30%=9650%; = onset of=20 action 2=964 mo; toxicities: retinopathy, myopathy, hyperpigmentation; = relative=20 efficacy ++)=20
    • Dose: 200 mg b.i.d.=20
    • Cost/mo: $36
  • Sulfasalazine (response rate > 30%; onset = of action=20 2=963 mo; toxicities: dyspepsia, hemolysis in glucose-6-phosphate = dehydrogenase=20 deficiency; relative efficacy ++)=20
    • Dose: 1 g b.i.d. or t.i.d.=20
    • Cost/mo: $38
  • Anticytokines=20
    • TNF inhibitors=20
      • Etanercept (response rate 50%=9670%; onset = of action=20 2=964 wk ; toxicities: injection-site reaction, infections; = relative=20 efficacy +++)=20
        • Dose: 25 mg S.C. twice a week=20
        • Cost/mo: $1,145
      • Infliximab (response rate 50%=9670%; onset = of action=20 2=964 wk; toxicities: infections; relative efficacy +++)=20
        • Dose: 3=9610 mg/kg I.V. q. 8 wk with=20 methotrexate
      • Adalimumab (response rate 50%=9670%; onset = of action=20 2=964 wk; toxicities: injection-site reactions, infections; = relative=20 efficacy +++)=20
        • Dose: 40 mg S.C. q. 2 wk =
      • Anakinra (response rate 30%; onset of = action 1=963 mo;=20 toxicities: injection-site reactions, infections; relative = efficacy + to=20 ++)=20
        • Dose: 100 mg/day S.C.
      • Prednisone (response rate > 90%; onset = of action=20 < 1 wk; toxicities: skin atrophy, cataracts, osteoporosis, = avascular=20 necrosis; relative efficacy +++)=20
        • Dose: 5=9610 mg/day=20
        • Cost/mo: $8 =
  • Immunosuppressants=20
    • Azathioprine (response rate 30%=9650%; onset = of action=20 2=963 mo; toxicities: hematologic, immunosuppression, cholestasis; = relative=20 efficacy ++)=20
      • Dose: 100=96150 mg/day=20
      • Cost/mo: $7
    • Cyclosporine (response rate 30%; onset of = action 2=963=20 mo; toxicities: renal (irreversible), hypertension, hypertrichosis,=20 immunosuppression; relative efficacy ++)=20
      • Dose: 2.5=965.0 mg/kg/day=20

Physical Therapy

  • Maintain activity=20
  • Passive range-of-motion exercises help prevent = contractures
  • Isometric and isotonic exercises build muscle = strength,=20 help preserve function
  • Aerobic training (especially water = exercises)=20

Surgery

  • Indicated for intractable pain, impaired = function=20
  • Dorsal hand synovectomy may prevent extensor = tendon=20 ruptures=20
  • Frayed menisci and other loose bodies that = interfere=20 with function can be removed=20
  • In the hands and wrists, operations on = periarticular=20 structures (e.g., repair of capsules and replacement of tendons) may = restore=20 appearance and function=20
  • Release of carpal tunnel compression usually = relieves=20 pressure on the median nerve=20
  • Arthroscopic surgery to remove cartilaginous = fragments=20 and for partial synovectomy may be useful in large, accessible joints = with=20 proliferative synovitis=20
  • Fusion to stabilize joint and relieve pain =
  • Total replacement for joints to restore = function=20
3D""bac= k to=20 top

Best References

Furst DE, et al: Ann Rheum Dis 62(suppl 2):2, = 2003 [PMID=20 14532138]

Misischia RJ, et al: Expert Opin Investig Drugs = 11:927 2002=20 [PMID 12084003]

Aletaha D, et al: Clin Exp Rheumatol 21(5 suppl = 31):S169,=20 2003 [PMID 14969071]

July=20 2006

=A9 2008 BC Decker Inc. All rights reserved. =