Rheumatoid Arthritis (RA)

At a Glance

Rheumatoid arthritis (RA) classically presents as a symmetrical arthritis, although a single large joint synovitis may be the initial presenting symptom. Patients of any age or sex may be affected; however, the disease most often occurs in young, middle-aged women. A patient with swelling of at least 1 large or multiple small joints that cannot be associated with another defined clinical condition should be tested for RA. The most commonly affected joints are the metacarpophalangeal and the proximal interphalangeal joints; however, other joints, both large and small, may be affected. Morning stiffness lasting more than 30-60 minutes is highly indicative of RA or other inflammatory arthritic conditions. The more joints that are affected and symptoms lasting more than 6 weeks increase the likelihood of RA.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The 2010 Rheumatoid Arthritis Classification Criteria include two laboratory test categories. The first category is serology, which includes a rheumatoid factor assay (RF) and an anti-cyclic citrullinated peptide assay (anti CCP). The second category is an acute phase reactant detection, consisting of a C-reactive protein (CRP) and/or an erythrocyte sedimentation rate (ESR). (Table 1)

Table 1.

Test Results Indicative of the Disorder
Rheumatoid Factor Anti-CCP Antibody C-Reactive Protein
Reference ranges may vary, but normally values >20 IU/ml are considered positive; however, most RA patients have values >160 IU. As with rheumatoid factor, values >20 are normally considered positive; however, most RA patients will have strongly positive results (i.e., >60 units). Abnormally high values are associated with, but not diagnostic of RA. Reference ranges may vary but are often <0.6-0.8 mg/dl. The ultrasensitive CRP assay is not used for RA diagnosis.

The laboratory should report quantitative values for each of these assays. A positive/negative result is of little significance. At least one test result from each category is necessary for a definitive diagnosis. Additional blood tests that may be ordered in a patient presenting with RA-type symptoms include a complete metabolic panel, complete blood count (CBC), complement studies, and an anti-nuclear antibody, which can help to differentiate RA from other autoimmune diseases, such as systemic lupus erythematosus or mixed connective tissue disease. Newer, multiplex autoimmune panels that include rheumatoid factor and/or anti CCP as components may also be used.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Immunosuppressive medications may reduce the sensitivity of the serologic and acute phase reactant assays. RF may be elevated at low levels in other autoimmune diseases. Both CRP and ESR are non-specific indicators of inflammation and may be elevated in infections or injury, as well as in other rheumatic or autoimmune diseases. Hepatitis C is often associated with a cryoglobulin that may have rheumatoid factor activity.

What Lab Results Are Absolutely Confirmatory?

No laboratory test is absolutely confirmatory for RA. However, according to the 2010 ACR guidelines, a strongly positive RF or anti CCP assay in the presence of more than four small joint involvement confirms the diagnosis of RA. However, the guidelines direct that either a CRP or an ESR test must be performed, even in the presence of multiple joint synovitis and a positive serologic assay.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Anemia, thrombocytosis, leukocytosis, and low albumin levels may be present in RA patients but are non-specific findings. In addition to a standard RF assay, a cryoglobulin test may be useful. Types 2 and 3 cryoglobulins have rheumatoid factor activity. Positive results may be associated with RA or possibly Hepatitis C infection. A synovial fluid examination may be ordered if the serum tests are all negative. The fluid from an RA patient will likely show a leukocytosis and may have low C3 and C4 complement levels. Normal synovial fluid complement component concentrations are approximately one-third of that found in serum. Synovial fluid analyses are not included in the specific RA classification scheme, however.

More recently, biomarkers, such as Interleukin 18, have been shown to be elevated in RA. However, no clinical assays are currently available for these proteins. RA is associated with HLA DR4, although this assay is not routinely performed in the diagnostic regimen.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

There are no documented drug interferences in these assays. RF and CRP results obtained by nephelometry may be falsely elevated in lipemic sera or sera containing other particulates.

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