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Medicine in Brief, Cases that Test Your Skills

Rheumatoid arthritis Dx, bariatric surgery and mortality, prostate cancer screening

Vol. 7, No. 5 / May 2008

Principal Source: Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med 2007;146:797-808.

Discussant: Robert M. McCarron, DO

Dr. McCarron is assistant professor, departments of internal medicine and psychiatry and behavioral sciences, University of California, Davis. He is CURRENTPSYCHIATRY’Ssection editor for medicine/psychiatry interface.

Medicine in Brief summarizes discoveries, clinical tests, or guidelines published in internal medicine literature that can affect psychiatric patients and practice. This information is intended to help you:

  • keep current with important developments in internal medicine
  • knowledgeably discuss these developments with medical colleagues
  • determine when to refer patients to a primary care physician or specialist
  • manage psychiatric issues while your patients undergo evaluation or treatment for a medical condition.

Up to 70% of patients with rheumatoid arthritis (RA) have a comorbid depressive or anxiety disorder, and depression is estimated to be 2 to 3 times more prevalent in RA patients than in the general population. 1 Until recently, rheumatoid factor (RF)—an antibody directed against a specific portion of immunoglobulin G—was the only serologic test for RA. Although included in American College of Rheumatology diagnostic criteria, RF has a relatively low specificity for RA (85%).

A new test—the anti-cyclic citrullinated peptide antibody (anti-CCP)—is highly specific for RA (96%) and thus less likely than RF to give a false-positive result. RF often is detected in non-RA patients, including the elderly and persons with hepatitis C, Sjögren syndrome, and systemic lupus erythematosus. The anti-CCP test’s sensitivity (67%) is roughly equal to that of RF (69%).

Anti-CCP can rule out other conditions that might mimic RA 2 —such as osteoarthritis ( Table 1 )—and is a key diagnostic tool to identify early-onset RA. Early detection of RA can lead to a timely primary care referral, use of disease-modifying medications, and improved clinical outcome.

Table 1

Is joint pain rheumatoid arthritis (RA) or osteoarthritis (OA)?




Joints involved



Joint complaints

‘Boggy,’ soft, tender

Bony hypertrophy

Joint stiffness

Worse after prolonged rest

Painful after exercise

Radiographic changes

Decalcification and erosion

Joint space narrowing

Laboratory findings

Positive anti-CCP

Normal anti-CCP

anti-CCP: anti-cyclic citrullinated peptide antibody; DIP: distal interphalangeal; MCP: metacarpophalangeal; PIP: proximal interphalangeal

A single test result is not a definitive RA diagnosis ( Table 2 ). A variety of physical, laboratory, and radiologic findings are required to make the diagnosis and initiate therapy. If your patient’s pain is consistent with RA, however, consider ordering a serum RF and anti-CCP to assist the primary care practitioner with prompt diagnosis and treatment. Both erythrocyte sedimentation rate and C-reactive protein have low specificity for RA and should not be included as part of the diagnostic workup.

RA diagnosis. RA is an autoimmune disorder that causes joint pain and deformity, multiple extra-articular manifestations, and disability. It affects 1% to 2% of Americans and 3 times as many women as men. Most adult RA patients initially present with joint swelling and pain between ages 35 to 55. 3

Consider screening for RA if your patient complains of joint pain or stiffness that is worse in the morning or after several hours of inactivity. Although atypical presentations occur, the presence of these RA characteristics warrant further inquiry: 4

  • a first-degree relative with RA
  • symmetrical joint involvement
  • peripheral joint involvement such as metacarpophalangeal (MCP) joints
  • proximal interphalangeal (PIP) or wrist joints involvement
  • age >35 years.

Table 2

American College of Rheumatology
diagnostic criteria for rheumatoid arthritis (RA)*



Morning stiffness

Duration of ≥1 hour after prolonged inactivity indicates a severe inflammatory process

Arthritis involving ≥3 joints

Usually metacarpophalangeal (MCP), proximal interphalangeal (PIP), wrist, elbow, knee, and ankle joints, rarely the lower back or shoulder; look for soft tissue swelling or effusion in the area of the affected joint

Arthritis of the hand

≥1 MCP, PIP, or wrist joint is involved

Symmetric arthritis

Initial symptoms may be asymmetric, and absolute symmetry is not needed for a diagnosis

Rheumatoid nodules

Size and degree of tenderness of subcutaneous nodules over bony prominences or tendons is variable

Serum rheumatoid factor (RF)

RF has low specificity for RA compared with anti-cyclic citrullinated peptide antibody (anti-CCP); although a positive anti-CCP test is not formally part of the diagnostic criteria, it should be part of a RA assessment

Radiographic changes

Usually of the hand or wrist; bony erosions and localized decalcifications are indicators of RA

* RA diagnosis requires presence of ≥4 criteria. The first 4 must have been present ≥6 weeks. Also consider the anti-CCP test an important diagnostic marker

Source: Reference 4

Osteoarthritis (OA) is characterized by bony hypertrophy, whereas with RA affected joints tend to feel slightly warm, soft or “boggy,” and are painful to the touch. Patients with OA usually do not have PIP joint pain but instead experience tenderness over the distal interphalangeal (DIP) joints.

Practice Points

  • Although most psychiatrists do not diagnose and treat a patient for RA, a basic understanding of diagnostic criteria can inform your decision to refer your patient to a primary care practitioner.
  • Many patients with RA also suffer from depression and anxiety and should be assessed for psychiatric disorders. Consider ordering anti-CCP and serum RF tests when you suspect a patient has RA.
  • The anti-CCP test is associated with fewer false-positive results than RF serum tests.
  • Early morning stiffness that lasts ≥1 hour and symmetrical MCP and PIP joint pain can indicate RA.

Related resources


Dr. McCarron is a consultant to Eli Lilly and Company.


1. Isik A, Koca SS, Ozturk A, Mermi O. Anxiety and depression in patients with rheumatoid arthritis. Clin Rheumatol 2007;26(6):872-8.

2. Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med 2007;146:797-808.

3. Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet 2001;358:903-11.

4. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.

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