What does a vial of blood or joint fluid reveal to your doctor
by Dr Anuradha Venugopalan

More than for most other diseases, the diagnosis and treatment of arthritis require a hands-on approach. By examining your tender joints and muscles and listening to your description of your symptoms and their severity, a doctor can usually get a pretty good idea of what's going on inside your body. But there are many times when a doctor needs information that only a laboratory examination of bodily fluids and tissues can reveal. When he needs to confirm a diagnosis, monitor disease progress or medication effectiveness, or determine if the drugs you're taking are causing potentially dangerous – but not evident – side effects, lab tests are in order.

The majority of lab tests are performed on blood because it is easily and safely sampled and it holds many microscopic clues to what's going on throughout the body. Other tests may require urine, joint fluid or even small pieces of skin or muscle.

The following blood tests are commonly performed to detect or evaluate rheumatologic disorders, including systemic lupus erythematosus (SLE), scleroderma, blood vessel inflammation (vasculitis) and types of arthritis (osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout and ankylosing spondylitis).

Rheumatoid factor (RF)-  This test is designed to detect and measure the level of an antibody that acts against the blood component gamma globulin, this test is often positive in people with rheumatoid arthritis (RA). About 80% of patients with RA test positive for rheumatoid factor, so this test is considered extremely useful for confirming a diagnosis of this type of arthritis.

RF alone cannot be used for diagnosis of rheumatoid arthritis. Around 15% to 20% of patients with rheumatoid arthritis never have RF positivity, and 2% to 10% of healthy persons are RF positive. Hence, positive RF alone does not confirm rheumatoid arthritis and negative RF does not exclude it.

RF is detected in a wide variety of rheumatic (Cryoglobulinemia, Sjogren's Syndrome, SLE, Systemic Sclerosis) and nonrheumatic conditions (infections, malignancy, bacterial endocarditis).

The gold standard method for RF testing is nephelometry. Other common methods are turbidometry and latex agglutination. The normal value of RF is below 40 IU.ml.

Anti-cyclic citrullinated peptide (anti-CCP) - Also called anti-citrullinated protein antibodies (ACPA), this test (like the test for rheumatoid factor) looks for the presence of a particular autoantibody that is present in approximately 60-80 percent of people with RA. While most patients with anti-CCP antibodies are also positive for rheumatoid factor, the RF antibody can occur in patients with many other conditions, including an infection. Anti-CCP is more specific for RA and is becoming the preferred test.

Two of the most important clinical uses of this test are its high specificity for the disease and the presence of anti-CCP antibodies in early-phase rheumatoid arthritis. Anti-CCP antibodies can appear in the circulation several years before the onset of rheumatoid arthritis. The presence of anti-CCP antibodies in early disease is highly predictive for more-rapid progression of disease, meaning patients with anti-CCP antibodies have significantly more joint damage than patients without this antibody. Hence, all patients in whom RA is suspected on clinical grounds should be tested for anti-CCP antibody

Antinuclear antibody (ANA) – Commonly found in the blood of people who have lupus, ANAs (abnormal antibodies directed against the cells' nuclei) can also suggest the presence ofpolymyositis, scleroderma, Sjogren's syndrome, mixed connective tissue disease or rheumatoid arthritis. Antinuclear antibodies (ANAs) have been detected in the serum of patients with many rheumatic and nonrheumatic diseases as well as in healthy persons.

The most common methods used to detect and characterize these ANAs include immunofluorescence microscopy (IIIF), enzyme-linked immunosorbent assay (ELISA).

There are different types of ANAs based on their target antigen. The staining pattern seen on indirect immunofluorescence (IIF) gives some indication of the specificity of the antibodies. ). Identification of the specificity for extractable nuclear antigens (ENA) is warranted because this can further differentiate between the distinct types of autoimmune connective tissue diseases. Hence, a positive ANA test should be followed by an ANA-Western Blot or RNA and anti-DNA antibodies assay.

Anti-DNA Antibodies- Antibodies to dsDNA are often measured in SLE and are commonly referred to as anti-DNA antibodies. They are very useful in the diagnosis of SLE and assessment of disease activity, and they are associated with lupus nephritis.The most commonly used techniques for measuring anti-dsDNA antibodies are ELISA and immunofluorescence. Not all patients with SLE have positive anti-dsDNA antibodies; therefore, a negative test does not exclude the diagnosis of SLE.

Complete blood count-a general test that measures the amounts of various blood cells—can provide clues to the presence of inflammation, which tends to increase levels of white blood cells and platelets and decrease the amount of red blood cells.

Erythrocyte sedimentation rate (ESR)- ESR refers to the rate at which red blood cells, or erythrocytes, settle at the bottom of a special tube to form a sediment. The ESR is increased in many rheumatologic disorders.  ESR can be greatly influenced by the shape and number of red blood cells as well as other plasma constituents. ESR increases steadily with age, and the upper limit varies with sex; hence, ESR is difficult to interpret compared to CRP.

C-reactive protein (CRP) - CRP is a substance produced by the liver in response to inflammation. CRP levels are an even better indication than ESR of the amount of inflammation present. In people with rheumatoid arthritis, if the CRP is high, it suggests that there is significant inflammation or injury in the body.

Both CRP and ESR levels are used to monitor disease activity and to monitor how well someone is responding to treatment.

Blood chemistry screen – 
Liver function test, blood urea and creatinine and serum lipids are general tests that can help to identify problems in the body's organs such as liver, heart and kidney. Certain types of inflammatory arthritis, including RA, can affect kidney function, as can certain arthritis drugs.

Uric acid- The blood test for this substance is primarily used to detect gout, a form of arthritis that typically affects the joints of the feet.  Uric acid levels may also be elevated in some kidney disorders and other conditions that are associated with excessive tissue destruction.

Urine Tests
Several different tests may be done on a urine sample to determine its contents. The tests show whether the urine contains red blood cells, protein, or a variety of abnormal substances, none of which is normally present. The detection of these substances may indicate kidney damage in certain rheumatic diseases, such as lupus.

A 24-hour urine test evaluates all the urine collected over a 24-hour period. Sometimes the creatinine passed in a 24-hour urine specimen is measured to provide a clearer picture of kidney function than the creatinine blood test. Uric acid, calcium, and protein tests sometimes must also be done on a 24-hour sample.

Joint fluid tests – Inserting a needle into a joint and aspirating, or removing, synovial fluid from it can provide a doctor with valuable information. (Synovial fluid is the slippery fluid that fills a joint, providing smoother movement.). It generally causes no more pain than drawing blood. An examination of the fluid may reveal what is causing the inflammation, such as uric acid crystals, a sure sign of gout, or bacteria, a sign of infection.

In addition, aspiration sometimes can relieve the pain of a badly swollen joint. Many a times a corticosteroid is injected through the needle to reduce inflammation for an extended period of time-up to three months in many cases and for months or years in a few instances.

HLA tissue typing – Human leukocyte antigen (HLA) tissue typing tests detect the presence of certain "genetic markers" or traits in the blood. For example, B-27 is a genetic marker that nearly always is present in people with ankylosing spondylitis (a disease involving inflammation of the spine and sacroiliac joint) and Reiter's syndrome (a disease involving inflammation of the urethra, eyes, and joints). This test also is positive in five to 10 percent of the healthy population.

Other Special Tests:
Complement tests- This test involves the reaction of antibodies with antigens. These tests usually are reserved for diagnosing or monitoring people with active lupus. Those people with lupus frequently have lower-than-normal amounts of complement, especially if the kidneys are affected.

Muscle enzyme tests- (CPK, aldolase) measure the amount of muscle damage. In some rheumatic diseases, damaged muscles release certain enzymes into the blood.

Biopsies
To help confirm a diagnosis or check on the status of disease activity, a doctor may order a biopsy, or removal small piece of tissue, to be examined under a microscope. Three of the most common biopsies include skin, muscle, and kidney biopsies. Skin biopsies usually are done to aid the diagnosis of lupus; vasculitis (inflammation of blood vessels); psoriatic arthritis (inflammation of joints and scaly, inflamed skin), or other forms of arthritis that involve the skin.

Muscle biopsies are similar to skin biopsies, and are used to look for signs of damage to the muscle fibers. This information can help confirm the diagnosis of polymyositis or vasculitis.

Kidney biopsies usually are done to check for signs of damage from a disease such as lupus. Other biopsies which are done on a less frequent basis are synovial, lung, salivary gland, and blood vessel biopsies. Liver biopsies occasionally are done to check for signs of damage in people receiving methotrexate for rheumatoid arthritis.

Lab Tests Limitations

Despite their many benefits, lab tests have their limitations. Some may show negative results even when a person has the disease being tested for; others may be positive in people who don't have – or may never develop – a particular disease. Not all forms of arthritis can be confirmed by lab tests. Other tests, including X-rays, various types of angiograms (studies of blood vessels) and magnetic resonance imaging (MRI), may be required to diagnose osteoarthritis, determine the cause of chronic back pain, or examine internal organs affected by some forms of arthritis.Even so, lab tests are essential to the diagnostic and treatment process. The right tests, along with your doctor's own observations and your participation in the process, can help you get the safest and most effective treatment for your disease.