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Blood Tests for the Diagnosis of Arthritis

According to the Arthritis Foundation, if you have signs or symptoms of arthritis for more than two weeks, it is time to see a doctor. These warning signs include:

  • Joint pain
  • Stiffness
  • Swelling
  • Difficulty moving a joint

Blood tests can help diagnose arthritis, monitor treatments, and track disease activity.

Laboratory blood tests are valuable diagnostic tools. They are usually not definitive when considered alone. The entire clinical picture of a patient, and the patient's history must be evaluated along with laboratory test results in order to produce an accurate diagnosis.When diagnosing, your doctor will look for very specific signs, symptoms, and disease characteristics. Your doctor will also consider your medical history, physical examination, blood tests, and imaging studies.

What blood tests are commonly ordered to diagnose and monitor arthritis?

Rheumatologists (doctors who specialize in the treatment of arthritis) typically order blood tests to help confirm or exclude a clinical diagnosis, a rheumatologist might order the following blood tests on the basis of your history and clinical examination to diagnose different types of arthritis:

For example, consider a patient who has a 3 month history of prolonged morning stiffness associated with pain and swelling of the wrists or hand. In this patient, the following blood tests might be ordered to help confirm a diagnosis of rheumatoid arthritis:

The presence of a positive RF or CCP in this patient would help confirm a diagnosis of rheumatoid arthritis (RA). On the other hand, up to 30 % of patients with RA may not have these antibodies, especially early in their disease. In addition, the presence of a RF, especially at a low level is not uncommon in patients who do not have, and never will develop RA.

The anti-CCP antibody is more likely to be associated with RA, so if elevated at a high level, the patient without typical manifestations of RA may be more likely to develop the disease.

The other two blood tests mentioned are the ESR and CRP. These blood tests measure inflammation and are typically elevated in patients with active RA. Normal levels do not rule out RA, but those patients may be less likely to develop damage in their joints than patients with high levels of inflammation, especially an elevated CRP.

An anti-nuclear antibody (ANA) is an important test in our example patient to evaluate for systemic lupus erythematosus or SLE. While low levels of ANA are common in RA, high levels of ANA in this example patient may indicate possible lupus, especially if the CCP and RF are negative.

Finally, on subsequent visits, the RF and CCP are not typically re-ordered if positive. On the other hand, the ESR and CRP are frequently ordered as they can help confirm (in addition to the patients history and exam) whether the arthritis is active or in remission.

Monitoring the blood work

Monitoring the blood workof patients is an important part of the medical care for arthritis patients. Many of the medications used may increase the risk of liver, kidney and blood abnormalities. Fortunately, these problems are uncommon, but when they occur, can be very serious. As a result, doctors will periodically obtain blood work to help pick up problems before they become apparent clinically.

Lets take two common medications used to treat arthritis. The first is ibuprofen. Ibuprofen is considered a nonsteroidal anti-inflammatory drug or NSAID. While rare, these types of medications have been associated with kidney and liver failure. Monitoring the blood for these abnormalities typically picks up the problem early so the medication can be discontinued without any long term problems. In addition, the finding of a low red blood count or anemia can alert your doctors to the possibility that you may be developing a bleeding ulcer.

Methotrexate, a common rheumatoid arthritis (RA) medication, can be associated with liver damage and blood abnormalities such as a low white blood count. If the white blood count gets too low, it can increase the risk of infection.

In addition to monitoring blood for toxicity, rheumatologists will also typically order blood tests such as a sedimentation rate and C-reactive protein in RA patients to assess their response to treatment and a sedimentation rate and double stranded DNA in lupus patients.

What blood tests are commonly ordered and what do they tell a rheumatologist about an individual patient?

What is Rheumatoid Factor?

Rheumatoid factor is an immunoglobulin (antibody) which can bind to other antibodies. Antibodies are normal proteins found in the blood which function within the immune system. Rheumatoid factor though is not normally found in the general population (only found in about 1-2% of healthy people). The incidence of rheumatoid factor increases with age and about 20% of people over 65 years old have an elevated rheumatoid factor.

A blood test is used to detect the presence of rheumatoid factor. The blood test is commonly ordered to diagnose rheumatoid arthritis. Rheumatoid factor is present in 80% of adults who have rheumatoid arthritis but there is a much lower prevalence in juvenile rheumatoid arthritis. The incidence of rheumatoid factor increases with duration of disease in rheumatoid arthritis: at 3 months the incidence is 33%, while at one year it is 75%. Up to 20% of rheumatoid arthritis patients remain negative for rheumatoid factor (also known as "seronegative rheumatoid arthritis") throughout the course of their disease.

What does anti-CCP indicate?

Anti-CCP, which stands for anti-cyclic citrullinated peptide antibody, is a new and exciting blood test to help doctors confirm a diagnosis of rheumatoid arthritis.

Anti-CCP is a very useful test to order during the diagnostic evaluation of a person who may have rheumatoid arthritis. If present in such a patient at a moderate to high level, it not only confirms the diagnosis but also may indicate that the patient is at increased risk for damage to the joints. (Low levels of this antibody are less significant.) In the past, doctors relied on another antibody, the rheumatoid factor (RF) to help confirm a diagnosis.

While the rheumatoid factor is more common in rheumatoid arthritis patients, many patients with a positive test do not have rheumatoid arthritis. Furthermore, the presence of the rheumatoid factor has less prognostic significance than the CCP. Of interest is that if your rheumatoid factor is negative, you are less likely to have a positive CCP. Both blood tests are recommended in the initial evaluation of a patient with suspected rheumatoid arthritis.

Anti-CCP antibodies are potentially important surrogate markers for diagnosis and prognosis in rheumatoid arthritis (RA), because they:

  • Are as sensitive as, and more specific than, IgM rheumatoid factors (RF) in early and fully established disease
  • May predict the eventual development into RA when found in undifferentiated arthritis
  • Are a marker of erosive disease in RA

may be detected in healthy individuals years before onset of clinical RA

The presence of a positive RF or CCP in this patient would help confirm a diagnosis of rheumatoid arthritis (RA). On the other hand, up to 30 % of patients with RA may not have these antibodies, especially early in their disease. In addition, the presence of a RF, especially at a low level is not uncommon in patients who do not have, and never will develop RA. The anti-CCP antibody is more likely to be associated with RA, so if elevated at a high level, the patient without typical manifestations of RA may be more likely to develop the disease.

What is Erythrocyte sedimentation rate? "ESR"

Erythrocyte sedimentation rate (ESR) is a diagnostic test for inflammation. The test measures the rate at which red blood cells fall to the bottom of a tube over time. An increased sedimentation rate corresponds to increased non-specific inflammation in the body. It is often called "sedrate" for short.

What Is CRP?

It is not a new test, but it is a test in the news. CRP, also known as C-Reactive Protein, is a test which measures the concentration in blood serum of a special type of protein produced in the liver that is present during episodes of acute inflammation or infection. In the body, CRP plays the important role of interacting with the complement system, an immunologic defense mechanism.

As a blood test, CRP is not specific. A high result serves as a general indication of acute inflammation. In cases of inflammatory rheumatic diseases, such as rheumatoid arthritis and lupus, doctors can utilize the CRP test to assess the effectiveness of a specific arthritis treatment and monitor periods of disease flareup. It's value is as a general indicator, not specific.

It must be noted that even in known cases of inflammatory disease, such as rheumatoid arthritis and lupus, a low CRP level is possible, and is not indicative of no inflammation.

Normally there is no CRP in blood serum. From Lab Tests Online, "a high or increasing amount of CRP in your blood suggests that you have an acute infection or inflammation. Although a result above 1 mg/dL is usually considered high for CRP, most infections and inflammations result in CRP levels above 10 mg/dL".

A positive CRP may be an indicator of several conditions, including:

  • Rheumatoid arthritis
  • Rheumatic fever
  • Cancer
  • Tuberculosis
  • Pneumonia
  • Heart attack
  • Lupus

A positive CRP also can be detected during the last half of pregnancy or with the use of oral contraception.

Both CRP and ESR give similar information about non-specific inflammation. CRP appears and disappears more quickly than changes in ESR. Therefore, your CRP level may drop to normal following successful treatment, whereas ESR may remain elevated for a longer period.

ANA (Antinuclear Antibody) Test

Antinuclear antibodies are a unique group of autoantibodies that have the ability to attack structures in the nucleus of cells. The nucleus of a cell contains genetic material referred to as DNA (deoxyribonucleic acid).There is an ANA (antinuclear antibody) test which can be performed on a patient's blood sample as part of the diagnostic process to detect certain autoimmune diseases.

To perform the ANA (antinuclear antibody) test, sometimes called FANA (fluorescent antinuclear antibody test), a blood sample is drawn from the patient and sent to the lab for testing.

Serum from the patient's blood specimen is added to microscope slides which have commerically prepared cells on the slide surface. If the patient's serum contains antinuclear antibodies (ANA), they bind to the cells (specifically the nuclei of the cells) on the slide.

A second antibody, commercially tagged with a fluorescent dye, is added to the mix of patient's serum and commercially prepared cells on the slide. The second (fluorescent) antibody attaches to the serum antibodies and cells which have bound together. When viewed under an ultraviolet microscope, antinuclear antibodies appear as fluorescent cells.

  • If fluorescent cells are observed, the ANA (antinuclear antibody) test is considered positive
  • If fluorescent cells are not observed, the ANA (antinuclear antibody) test is considered negative

Anti-DNA and Anti-Sm

Lupus patients have antibodies to the heredity material DNA (deoxyribonucleic acid). It is a useful diagnostic tool since it is unusual to find these antibodies in people who do not have lupus. The test is also a good monitoring tool since the levels of anti-DNA rise and fall with disease activity.

Lupus patients also have antibodies to Sm, another substance in the cell's nucleus. These antibodies also occur only in lupus patients. The test is not particularly useful in monitoring disease activity however.

Complement

The complement system is a complex set of blood proteins which are part of the body's defense system. These proteins are inactive until an antibody binds to an antigen and activates the complement system. The system produces factors which help destroy bacteria, and combat invaders with white cells. These reactions consume complement and leave depressed levels indicative of immune complex formation. Lupus patients often show decreased levels of total complement. The complement test may be helpful in tracking the disease activity of a lupus patient.

Uric Acid

Uric acid is a waste product normally present in the blood as a result of the breakdown of purines. Excessive amounts of uric acid can cause crystals to form in the joints and cause gout.

High levels of uric acid in the blood (known as hyperuricemia) can cause crystals to form which are deposited in the joints and tissues, causing painful gout attacks. Uric acid is the final product of purine metabolism in humans.

For certain types of systemic rheumatic diseases, biopsies of certain organs can provide important diagnostic information. Also, joint fluid analysis can provide a doctor with many details about the health of a person's joint.

HLA Tissue Typing

Human Leukocyte Antigens (HLA) are proteins on the surface of cells. Specific HLA proteins are genetic markers for some of the rheumatic diseases. Patients may be tested to see if they have the genetic markers. HLA-B27 has been associated with ankylosing spondylitis and other spondyloarthropathies. Rheumatoid arthritis is associated with HLA-DR4.

Self treating is not recommended for patients with new symptoms until the cause can be confirmed. The reason for this caution is that arthritis may be a symptom of a more serious condition such as lupus, rheumatoid arthritis, infection or malignancy. An accurate diagnosis leads the way to proper treatment.

Blood tests can help diagnose arthritis, monitor treatments, and track disease activity. If you have signs or symptoms of arthritis for more than two weeks, it is time to see a doctor. These warning signs include:

  • Joint pain
  • Stiffness
  • Swelling
  • Difficulty moving a joint

Click here to know more about Screening for Arthritis

Prof Fahim Khan Meet
Prof Fahim Khan
(MBBS,MD,MRCP London,FRCP London, FRCP Edin, FACP-Rheum)
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