ECASE #7

March 18-22

Kathy J. Hurlburt, MD

Case:  A 36 yo female presents to your office with complaint of pain and stiffness in her right wrist, MCP's and PIP's, now starting in her left wrist as well.  The pain and stiffness last 1-2 hours in the morning and have been progressively worse over the past few weeks.  She denies fever, chills, weight loss, rashes, myalgias, GI symptoms.

On exam she has soft tissue swelling and tenderness in the above stated joints. Her past medical history is unremarkable and she denies taking any medications, prescription, OTC, or herbals.  Labs show her rheumatoid factor is negative, ESR is elevated to 36, CBC, Chem 7, Hep B & C, and ANA/reflexive panel are negative.  Bilateral AP/Ball Catcher views of the hands show no erosions or bony decalcifications.

Questions

1. Does this pt meet the criteria for rheumatoid arthritis?
2. What is the utility of radiographs in evaluating RA? ESR?
3. What form of initial treatment would you choose? What additional baseline evaluation is necessary?

1. The criteria for the classification of RA from the American College of Rheumatology requires 4 of the 7 following:

• Morning stiffness in and around the joints lasting at least 1 hr before maximal improvement

• Arthritis of 3 or more jt areas simultaneously including:  R or L PIP, MCP, wrist, elbow, knee, ankle and MTP jts

• Arthritis of hand jts

• Rheumatoid nodules

• Serum Rheumatoid Factor - 85% will be RF+, studies show RF titers tend to correlate w/severe and unremitting disease, nodules, and extra-articular lesions. In the individual pt, however, the RF titer is of little prognostic value and serial titers are of no value in following the disease process.  A very small % of RF- pt's will seroconvert w/disease progression.

• Symmetric Arthritis

• Radiographic changes:  erosions or unequivocal bony decalcification
  This pt has morning stiffness, arthritis of 3+ joints, symmetrical (both wrists), and hand arthritis, and therefore meets the criteria.

2. X-Rays:  Radiographs are important to obtain once the disease has been diagnosed.  Progression as evidenced by x-rays is helpful in tailoring the patient's therapy, including a step-up to one of the biologic agents (Etanercept or Infliximab).
   
   ESR:  Typically the ESR correlates w/the degree of synovial inflammation, but this correlation varies greatly from patient to patient, and, rarely, a patient w/active inflammatory RA may have a normal ESR. The ESR is a useful tool, however, for following the course of inflammatory activity in an individual.  C-reactive protein may also be used to monitor the level of activity.

3. Drug therapy for RA is yided roughly into two groups:  those used primarily for the control of joint pain and swelling, and those intended to limit joint damage and improve long-term outcome.  NSAIDS are effective in treating pain, swelling, and stiffness, but have no effect on the disease course or risk of joint damage.  DMARDS (disease-modifying antirheumatic drugs), on the other hand, can often times accomplish both.  Recommended dosages and side effects of most RA DMARDS are:

For Mild Dz (few jts involved, ESR<30):   Plaquenil (hydroxychloroquine) or sulfasalazine +/- NSAIDS (naproxen and Ibup most commonly used)

ie - Hydroxychloroquine 400 mg/d +/- NSAID, and predn 3-5mg/d over a 1-3 month period.  Or, sulfasalazine up to 3 gm/d, although pt is not likely to respond to >2gm.

For new-onset RA w/marked sx's  (fatigue, low-grade fevers, wt loss, polyarticular dz), or pt's w/established dz:  Mtx

ie; MTX + NSAID + Predn 5-15/d, tapering predn over a 3-4 month period, consider adding plaquenil or sulfasalazine if only a partial to Mtx.

For failure of combination regimens:  Etanercept or Infliximab

-both are very expensive ($1000+/month), difficult to justify to insurance co's, and pt may be on a waiting list.

This pt probably fits into the milder disease category as she has no radiographic abnormalities and no constitutional symptoms, although most rheumatologists would not disagree with starting this pt on Mtx given her polyarticular disease and borderline ESR (to the cut off of 30).

Recommended baseline evaluations before starting a pt on a DMARD includes:

• Plaquenil - Eye exam (retinopathy occurs rarely when appriate dosages used)

• Sulfasalazine - CBC 2 wks x 3 months, then q 3 months

• MTX - CBC, ALT/AST, serum Alb q 8 wks

• Azathioprine - CBC q1-2 wks 1st month or w/dose change, then q1-3 months

• Leflunomide - CBC, AST/ALT q 8 wks

• Gold - CBC and UA q 1-2 wks for 1st 20 wks then at each injection

• Cyclosporin - Creat & BP q 2 wks for 1st 3 months, then q month

• Etanercept - none

• Infliximab - none

References

1. Fries JF, Williams CA, Morfeld D.  Reduction in long-term disability in patients with rheumatoid arthritis by disease-modifying antirheumatic drug-based treatment strategies.  Arthritis Rheum 1996;39:616-622.

2. Masi AT. Articular patterns in the early course of rheumatoid arthritis. Am J Med 1983;75:16-26.

3. Primer on the Rheumatic Diseases.  Edition 12.  2001;208-31.