Nejm 1990;322:1277

Cause:Genetic, associated w HLA DRB₁, DR₁, and DR₄ (Ann IM 1992;117:801, 869)

Pathophys:

Collagenase produced by granulation tissue (Nejm 1977;296:1017)

Suppressor T-cell defect; don’t suppress EBV antibody production normally, leads to chronic EBV antibody production? (Nejm 1981;305:1238); rv of all theories including EBV ones (Ann IM 1984;101:810)

Diagnostic criteria (Bull Rheum Dis 1988;38[5]:1) have 90% sensitivity and specificity if have 4 of following criteria:

1. early morning stiffness >6 wk;
2. arthritis involving 3 or more joints >6 wk;
3. wrist mcp or pip joint involvement;
4. symmetric arthritis;
5. rheumatoid nodules;
6. positive rheumatoid titer;
7. bony xray changes

(Epidem Rev 1990;12:247)

Adult female/male = 3:1, onset age 25-50 yr

Sx:Joint pain (100%), monoarticular arthritis (8%); insidious onset; rare fever

Si:Subcutaneous (rheumatoid) nodules over pressure points; evanescent rash (6%); arthritis and thick synovium

Chronic over decades; often improves during pregnancy (Nejm 1993;329:466)

• Peptic ulcers
• Septic arthritis, subtle (Ann IM 1969;70:147)
• Scleral malacia perforans and uveitis
• Pulmonary interstitial pneumonitis and fibrosis, empyema, pleuritis
• Pericarditis and aortic valvulitis (Nejm 1973;289:597)
• Sjögren’s syndrome (Sjögren's (Sicca) Syndrome)
• Felty’s syndrome (J Rheum 1989;16:864) (depressed white counts (Agranulocytosis (and Neutropenia)) frequent infections, sometimes splenomegaly, skin ulcers).
• Odontoid ligament laxity/rupture (Rheum Dis Clin N Am 1991;17:757; J Rheum 1990;17:134) (10%) (if on xray have >4-mm separation + neurologic si and sx, should have surgery) and other tendon/ligamentous rupture

Lab:

Joint fluid:Wbc ~40 000, poor mucin clot, protein = 4-5 gm %, C' decreased

Pleural fluid:Low glucose (<30 mg %); elevated LDH, protein >4 gm %, C' decreased (distinguishes from cancer)

Serol:Rheumatoid factor titers, 70% sens, 85% spec; anticyclic citrullinated peptide antibodies, 67% sens, 95% specif (Ann IM 2007;146:797)

Rx:

(Ann IM 2007;146:406, 459; Nejm 2004;350:2591)

Follow with buttoning or shoe-tying time, and BP cuff grip strength test with cuff starting at 30 mm (Ann IM 1994;120:26)

Medications (Ann IM 2001;134:695; Med Let 2000;42:57):

• Methotrexate (mtx) 15-30+ mg po q 1 wk, sc or im possible if po not helping; w 1 mg folate po qd helps toxicity w/o decr efficacy (Ann IM 1995;122:833); no cancer risk (Ann IM 1987;107:358); adverse effects: nausea and vomiting, pulmonary fibrosis, 10% get liver disease (Am J Med 1991;90:711)

w other drugs, like

• Tumor necrosis factor antagonists (Disease Modifying Antirheumatic Drugs (DMARD)) like infliximab (Remicade) 3 mg/kg iv wk 0, 2, 6, then q 8 wk (Arth Rheum 2005;52:3381); safe and effective (Ann IM 2002;137:726); adalimumab (Humira) IgG₁ recombinant monoclonal antibody to TNF; 40 mg injected q 2 weeks, golimumab (Simponi), or other biologic response-modifying drugs like abatacept, anakinra, leflunomide, or rituximab
• Steroids, into joints or 60 mg po tapered to 10 mg or less in 7 wk × 2 yr (Arth Rheum 2005;52:3381; Nejm 1995;333:142), 10 mg qd × 1st 6 mo of rx helpful by DBCT (Ann IM 2002;136:1); usually w bisphosphonate to slow osteoporosis
• Sulfasalazine 2-3 gm po qd
• Hydroxychloroquine 200 mg bid (retinopathy unlikely at <3.5 mg/lb) + sulfasalazine 500 mg bid (72% improved vs 50% at 1 yr—Nejm 1996;334:1287)
• Gold, 10 mg im, then 50 mg im q 1 wk × 20 wk, then decrease gradually to q 1 mo; rare used now because of doubts re efficacy (Ann IM 1991;114:437); adverse effects: rash, depressed wbc and/or platelets, proteinuria (10%), pulmonary infiltrates. Or oral form auranofin (Ridaura), rarely used
• Cyclosporine ~3 mg/kg/d po divided into bid doses (Nejm 1995;333:137), w methotrexate
• Leflunomide (Arava) (Nejm 2004;350:2167) 100 mg po qd × 3 d then 20 mg po qd
• Azathioprine
• Tetracyclines like minocycline or doxycycline 100 mg po bid (Ann IM 1995;122:81)
• D-penicillamine (Ann IM 1986;105:528) <1 gm qd, start at 250 mg qd, increase q3mo; rarely used because of adverse effects: rashes, depressed wbc and platelets, proteinuria, Goodpasture’s