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Rheumatoid Arthritis: Clues to Early Diagnosis

Rheumatoid Arthritis: Clues to Early Diagnosis

A 38-year-old African American woman sought medical care because of a 1-month history of painful, swollen hands. The patient, a hospital nurse, thought at first that her symptoms might be job-related, but she became concerned when the pain persisted and was frequently accompanied by morning stiffness that lasted some mornings for about half an hour. She tried acetaminophen and ibuprofen, which helped only slightly. She denied recent infections and other joint pain but complained of fatigue of recent onset. She also denied rash, alopecia, fever, chills, sweats, chest pain, cough, shortness of breath, photophobia, headaches, weakness, and back pain. Her symptoms interfered with a number of her daily activities. She has had a long monogamous relationship with her husband.

Physical examination revealed slight tenderness and mild swelling over the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints bilaterally but no erythema or warmth. Mild bilateral tenderness of the metatarsophalangeal (MTP) joints was also noted. All the other joints were normal. Inflammatory polyarthritis was a diagnostic consideration. Naproxen was prescribed, radiographic and laboratory studies were ordered, and a follow-up visit was scheduled.

At follow-up 2 weeks later, the patient still had joint pain and swelling, and her fatigue had worsened, although she had difficulty sleeping because of the pain. Plain radiographs of the hands and feet revealed periarticular soft tissue swelling around 2 of the MCP joints. Laboratory results were normal except for an erythrocyte sedimentation rate (ESR) of 46 mm/h. Results of tests for rheumatoid factor (RF), antinuclear antibodies, and parvovirus antibodies were negative. The patient was referred to a rheumatologist for further evaluation; however, the next available appointment was not for 4 months.

By the time the patient saw the rheumatologist, she was in considerable pain. Swelling, redness, and warmth were present bilaterally in the PIP, MCP, and MTP joints as well as in both wrists. Morning stiffness had increased to 2 hours. Plain radiographs revealed soft tissue swelling of both hands, accompanied by periarticular osteopenia in some MCP joints. Laboratory studies revealed positive RF and cyclic citrullinated peptide (anti-CCP) antibodies, decreased hemoglobin, and an elevated ESR. With these new findings, a definitive diagnosis of rheumatoid arthritis (RA) was made that satisfied the American College of Rheumatology (ACR) criteria.

This scenario illustrates the challenges inherent in recognizing RA in its early stages—when laboratory and radiologic markers of the disease have not yet become definitive and diagnostic classification criteria, as defined by the ACR (Tables 1 and 2),1 have not yet been fulfilled. In addition, it underscores the dire clinical consequences of waiting several months for a rheumatologist to confirm the primary care physician’s diagnosis of early RA and to partner with the rheumatologist to promptly implement the most appropriate therapeutic intervention. The need for this therapy is based on studies that show that joint destruction occurs early in RA and that therapy with DMARDs can retard this process, improve quality of life, reduce symptoms, and delay disability. These findings have led to the recommendation that DMARD therapy be initiated very early in the disease.

  Table 1 — The American College of Rheumatology revised criteria for classification of rheumatoid arthritis (RA)

Any 4 of the following criteria must be present to classify patients as having RA:
Morning stiffness for ≥ 1 h*
Arthritis of 3 or more joints*
Arthritis of hand joints (wrist, metacarpophalangeal, or proximal interphalangeal joints)
Symmetric arthritis*
Rheumatoid nodules
Serum rheumatoid factor (positive in < 5% of normal controls)
Radiographic changes (hand x-ray film changes typical of RA must include erosions or
unequivocal bony decalcification)

*Must be present for ≥ 6 weeks.
From Goronzy JJ, Weyand CM. Primer on the Rheumatic Diseases. 2001.1


Primary care physicians are usually the first to see patients with joint pain; consequently they represent the "front line" of RA care.2,3 This fact—coupled with the projection that the number of rheumatologists is expected to decline by 20% during the next 2 to 3 decades4—underscores the pivotal role that primary care clinicians are now expected to play in the early diagnosis of RA.

With the advent of DMARDs, early diagnosis of RA is no longer simply an academic exercise. However, in its early stages, RA resembles many other types of arthritic disorders, including systemic lupus erythematosus, viral infection, and undifferentiated seronegative polyarthritis. Nevertheless, a high index of suspicion for RA is crucial since we now have medications that—when used judiciously—can prevent or retard the development of intense pain, irreversible joint destruction, systemic complications, and progressive functional decline that affects at least 2 million Americans.1 RA is also associated with a decrease in life expectancy of 5 to 15 years secondary to comorbid illnesses that may be exacerbated by the underlying pathophysiologic mechanisms. Whether DMARDs can attenuate this drop in life expectancy is not known at this point, however.

What clinical clues point to RA? What laboratory tests should be ordered—and at what point? When is DMARD therapy appropriate? How can the primary care physician and rheumatologist work together to optimize care? Here I address these questions.

  Table 2 — Difficulties in making an early diagnosis of rheumatoid arthritis (RA)*

  • Classic features of RA take time to develop.
  • Many other diseases can present with symptoms similar to early RA.
  • There is no single clinical feature, laboratory test, or imaging study that allows a definitive diagnosis.

*Clinical diagnosis is based on a constellation of compatible features and exclusion of other diseases.



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