Tests

Normally, we have antibodies in our blood that are used to repell invaders into our body, such as virus and bacteria microbes. Antinuclear antibodies (ANAs) are unusual antibodies, detectable in the blood, that have the capability of binding to certain structures within the nucleus of the cells. The nucleus is the innermost core within the body's cells and contains the DNA, the genetic material. ANAs are found in patients whose immune system may be predisposed to cause inflammation against their own body tissues. Antibodies that are directed against one's own tissues are referred to as auto-antibodies.

The propensity for the immune system to work against its own body is referred to as autoimmunity. ANAs indicate the possible presence of autoimmunity and provide, therefore, an indication for doctors to consider the possibility of autoimmune illness. The ANA test was designed by Dr. George Friou in 1957. The ANA test is performed using a blood sample. The antibodies in the serum of the blood are exposed in the laboratory to cells. It is then determined whether or not antibodies are present that react to various parts of the nucleus of cells. Thus,the term anti-"nuclear" antibody. Fluorescence techniques are frequently used to actually detect the antibodies in the cells, thus ANA testing is sometimes referred to as fluorescent antinuclear antibody test (FANA). The ANA test is a sensitive screening test used to detect autoimmune diseases.

Autoimmune diseases are conditions in which there is a disorder of the immune system characterized by the abnormal production of antibodies (auto-antibodies) directed against the tissues of the body. Auto -immune diseases typically feature inflammation of various tissues of the body. ANAs are found in patients with a number of different autoimmune diseases, such as systemic lupus erythematosus, Sjogrens syndrome, rheumatoid arthritis, polymyositis, scleroderma, Hashimoto's thyroiditis, juvenile diabetes mellitus, Addison disease, vitiligo, pernicious anemia, glomerulonephritis, and pulmonary fibrosis.

ANAs can also be found in patients with conditions that are not considered classic autoimmune diseases, such as chronic infections and cancer. ANAs can be produced in patients with infections (virus or bacteria), lung diseases (primary pulmonary fibrosis, pulmonary hypertension), gastrointestinal diseases (ulcerative colitis, Crohn's disease, primary biliary cirrhosis, alcoholic liver disease), hormonal diseases such as(Hashimoto's autoimmune thyroiditis, Grave's disease), blood diseases (idiopathic thrombocytopenic purpura, hemolytic anemia), cancers (melanoma, breast, lung, kidney, ovarian and others), skin diseases (psoriasis, pemphigus), as well as in the elderly and those persons with a family history of rheumatic diseases.

Many medications can sometimes stimulate the production of ANAs, including procainamide (Procan SR), hydralazine, and dilantin. These are referred to as drug-induced ANAs. This does not necessary mean that any disease is present when these ANAs are "induced." Sometimes diseases are associated with these ANAs and they are referred to as drug-induced diseases. ANAs present different patterns depending on the staining of the cell nucleus in the laboratory: homogeneous or diffuse; speckled; nucleolar; and peripheral or rim. While these patterns are not specific for any one illness, certain illnesses can more frequently be associated with one pattern or another.

The patterns then can sometimes give the doctor further clues as to types of illnesses to look for in evaluating a patient. For example, the nucleolar pattern is more commonly seen in the disease scleroderma. The speckled pattern is seen in many conditions and in persons who do not have any autoimmune disease. ANAs can be found in approximately 5% of the normal population, usually in low titers (low levels). These persons usually have no disease. Titers of lower than 1:80 are less likely to be significant. (ANA titers of less than or equal to 1:40 are considered negative). Even higher titers are often insignificant in patients over 60 years of age. Ultimately, the ANA result must be interpreted in the specific context of an individual patients symptoms and other test results. It may or may not be significant in a given individual.

There are several different types of ANAs. Usually,when an ANA is ordered,for example,in a primary care physician's office,the total ANA is reported. If it is abnormally high,it provides a clue to the underlying diagnosis but a further test called an ANA reflexive panel is usually ordered. This test breaks down the ANA into its different types which provides much more valuable information to the rheumatologist about the underlying disease. This test could better interpret the ANA test to say whether or not this is tendering towards lupus or whether it's the ANA that can be seen in some RA patients.

Laboratory tests for RA diagnosis is,normally,relatively few. The sed rate (ESR) or the CRP measure the current inflammation that the patient is experiencing and is also,a useful tool for monitoring purposes. A complete blood count is normally taken. X-rays at onset may be useful for later, monitoring purposes. Systemic involvement,testing,is mandatory,as well as patient's medical history,current and past.

The complete blood count is the calculation of the cellular (formed elements) of blood. These calculations are generally determined by specially designed machines that analyze the different components of blood in less than a minute. A major portion of the complete blood count is the measure of the concentration of white blood cells, red blood cells, and platelets in the blood. The complete blood count (also called CBC) is generated by testing a simple blood sample. The values generally included in a complete blood count: White blood cell count (WBC). The number of white blood cells in a volume of blood. Normal range varies slightly between laboratories but is generally between 4,300 and 10,800 cells per cubic millimeter (cmm). This can also be referred to as the leukocyte count and can be expressed in international units as 4.3 - 10.8 x 109 cells per liter.

Automated white cell differential. A machine generated percentage of the different types of white blood cells, usually split into granulocytes, lymphocytes, monocytes, eosinophils, and basophils.

Red cell count (RBC). The number of red blood cells in a volume of blood. Normal range varies slightly between laboratories but is generally between 4.2 - 5.9 million cells/cmm. This can also be referred to as the erythrocyte count and can be expressed in international units as 4.2 - 5.9 x 1012 cells per liter.

Hemoglobin (Hb). The amount of hemoglobin in a volume of blood. Hemoglobin is the protein molecule within red blood cells that carries oxygen and gives blood its red color. Normal range for hemoglobin is different between the sexes and is approximately 13 - 18 grams per deciliter for men and 12 - 16 for women (international units 8.1 - 11.2 millimoles/liter for men, 7.4 - 9.9 for women).

Hematocrit (Hct). The ratio of the volume of red cells to the volume of whole blood. Normal range for hematocrit is different between the sexes and is approximately 45 - 52% for men and 37 - 48% for women.

Mean cell volume (MCV). The average volume of a red cell. This is a calculated value derived from the hematocrit and red cell count. Normal range is 86 - 98 femtoliters.

Mean cell hemoglobin (MCH). The average amount of hemoglobin in the average red cell. This is a calculated value derived from the measurement of hemoglobin and the red cell count. Normal range is 27 - 32 picograms.

Mean cell hemoglobin concentration (MCHC). The average concentration of hemoglobin in a given volume of red cells. This is a calculated volume derived from the hemoglobin measurement and the hematocrit. Normal range is 32 - 36%.

Red cell distribution width (RDW). A measurement of the variability of red cell size. Higher numbers indicate greater variation in size. Normal range is 11 - 15.

Platelet count. The number of platelets in a volume blood. Platelets are not complete cells, but actually fragments of cytoplasm from a cell found in the bone marrow called a megakaryocyte. Platelets play a vital role in blood clotting. Normal range varies slightly between laboratories but is in the range of 150,000 - 400,000/ cmm (150 - 400 x 109/liter).

A sedimentation rate is common blood test that is used to detect and monitor inflammation in the body. The sedimentation rate is also called the erythrocyte sedimentation rate because it is a measure of the red blood cells (erythrocytes) sedimenting in a tube over a given period of time. Sedimentation rate is often abbreviated as sed rate or ESR. A sedimentation rate is performed by measuring the rate at which red blood cells (RBCs) settle in a test tube. The RBCs become sediment in the bottom of the test tube over time, leaving the blood serum visible above. The sedimentation rate is simply how far the top of the RBC layer has fallen in one hour. The sedimentation rate increases with more inflammation. The normal sedimentation rate (Westergren method) for males is 0-15 millimeters per hour, females is 0-20 millimeters per hour. The sedimentation rate can be slightly more elevated in the elderly. The "sed" rate is a fairly sensitive, but not a perfect, detector of inflammation. Its abnormal elevation is dependent upon the duration and severity of the inflammation. It indicates possible inflammation when elevated. An elevated sedimentation rate is not seen in,e.g.,fibromyalgia or thyroid imbalance alone without an accompanying condition that is associated with inflammation.

Platelets are normal blood clotting elements that are produced in the bone marrow. Low platelet counts (thromobocytopenia = 150,000 per mm) are not common in patients with rheumatoid arthritis. When low platelet counts are noted they are usually a result of a medication, Felty's syndrome, or an underlying illness.

Many of the second-line medications used to treat rheumatoid disease require regular blood count monitoring because the can impair the normal function of the bone marrow. This can lead to a lowering of the platelet count. Generally, this response does eventually recover, but recovery is a function of the particular drug and the severity of the effect.

Felty's syndrome (rheumatoid arthritis, enlarged spleen, and low white blood counts) can be associated with low blood platelet counts, usually to a mild degree. This form of thrombocytopenia typically does not cause symptoms and usually requires no treatment.

Though uncommon, it is possible to develop another illness that could cause a low platelet count while having rheumatoid arthritis, such as a disease that would cause bone marrow abnormalities. Further, it is possible for rheumatoid arthritis to evolve into systemic lupus erythematosus, another rheumatic disease that is commonly associated with low platelet counts.

An initial step in detecting liver damage is a simple blood test to determine the presence of certain liver enzymes in the blood. Under normal circumstances, these enzymes reside within the cells of the liver. But when the liver is injured, these enzymes are spilled into the blood stream. Among the most sensitive and widely used of these liver enzymes are the aminotransferases. They include aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT). These enzymes are normally contained within liver cells. If the liver is injured, the liver cells spill the enzymes into blood, raising the enzyme levels in the blood and signaling the liver damage. The aminotransferases catalyze chemical reactions in the cells in which an amino group is transferred from a donor molecule to a recipient molecule. Hence, the names aminotransferases.

Medical terms can sometimes be confusing, as is the case with these enzymes. Another name for aminotransferase is transaminase. The enzyme aspartate aminotransferase (AST) is also known as serum glutamic oxaloacetic transaminase (SGOT); and alanine aminotransferase (ALT) is also known as serum glutamic pyruvic transaminase (SGPT). To put matters briefly, AST = SGOT and ALT = SGPT. AST (SGOT) is normally found in a diversity of tissues including liver, heart, muscle, kidney, and brain. It is released into serum when any one of these tissues is damaged. For example, its level in serum rises with heart attacks and with muscle disorders. It is therefore not a highly specific indicator of liver injury.

ALT (SGPT) is, by contrast, normally found largely in the liver. This is not to say that it is exclusively located in liver but that is where it is most concentrated. It is released into the bloodstream as the result of liver injury. It therefore serves as a fairly specific indicator of liver status. The normal range of values for AST (SGOT) is from 5 to 40 units per liter of serum (the liquid part of the blood).

A urinalysis is simply an analysis of the urine. Urinalysis can disclose evidence of diseases, even some that have not caused significant signs or symptoms. Therefore, a urinalysis is commonly a part of routine health screening. Examples of diseases that can be detected by urinalysis include diabetes mellitus, kidney diseases such as glomerulonephritis, and chronic infections of the urinary tract. Urinalysis consists of macroscopic urinalysis, urine dipstick chemical analysis, and microscopic urinalysis. Macroscopic urinalysis is the direct visual observation of the urine, noting its quantity, color, clarity or cloudiness, etc.

This microchemistry system permits qualitative (yes/no) and semi-quantitative analysis within a minute by simple observation. The color change occurring on each segment of a dipstick is read by being compared to a color chart. Dipsticks can, for example, be used to determine the urine's pH (acidity), specific gravity (density), protein content, glucose, ketones, nitrite content, and to determine an estimate of the number of white blood cells in the urine. Dipsticks, whether they be paper or plastic, have many advantages. They are simple, fast, convenient, easy to use, and they are the most cost-effective way to screen urine. However, what can be learned from a dipstick is limited by the design of the dipstick.

The microscopic urinalysis is the study of the urine under the microscope. It requires only a relatively inexpensive light microscope. The sample of urine is prepared in the laboratory and a drop of the urine sediment is put onto a glass slide.

Bone mineral density is a measured calculation of the true mass of bone. The absolute amount of bone as measured by bone mineral density (BMD) generally correlates with bone strength and its ability to bear weight. By measuring BMD, it is possible to predict fracture risk in the same manner that measuring blood pressure can help predict the risk of stroke. It is important to remember that BMD cannot predict the certainty of developing a fracture; it can only predict risk. The World Health Organization has used bone mineral density to define specific diagnostic categories: Normal: A value for BMD statistically within 1 standard deviation of an young adult. These people fall within the normal range. Low bone mass: A value for BMD statistically more than 1 standard deviation but less than 2.5 standard deviations than an average young adult. These people have an increased fracture risk but do not meet the criteria for osteoporosis.

Osteoporosis: A value for BMD statistically greater than 2.5 standard deviations below an average young adult. By these criteria, it is estimated that 30% of all postmenopausal Caucasian women have osteoporosis and that almost 60% have low bone mass. It should be noted that all normal values of BMD are based on Caucasian data. It is well documented that there is significant variation in BMD between ethnic groups. For example, African Americans in general have a greater BMD as compared to Caucasians of the same age and weight. Interpretation of results must take this difference into account.

Determining a persons BMD helps a doctor decide if therapy for osteoporosis is needed. In addition, if therapy is started, subsequent BMD measurements are used to monitor the effectiveness of treatment. The purpose of BMD testing is to: Help predict the risk of future fracture. Measure the amount of bone mass. Monitor the effectiveness of treatment. In subjects with low bone mass (as defined above), there is a 2 to 3 fold increase in the incidence of spinal fractures. In subjects with a BMD in the osteoporosis range, there is approximately a 5 times increase in the occurrence of fractures.

At present, the National Osteoporosis Foundation has recommended that testing be performed on all postmenopausal women under the age of 65 who have risk factors for osteoporosis (these include a previous history of fractures, low body weight, cigarette smoking, and a family history of fractures). In addition, it is recommended that all women over the age of 65 be tested, regardless of risk factors. It is also advised that anyone seeking therapy for osteoporosis be tested. These are guidelines only, and it should be remembered that testing is only indicated if it will influence treatment decision. For example, is the patient willing to be treated if the results are positive?

Arthroscopy is a surgical procedure in which the internal structure of a joint is examined for diagnosis and/or treatment using a tube-like viewing instrument called an arthroscope. Arthroscopy was popularized in the 1960s and is now commonplace throughout the world. Generally, it is performed by orthopedic surgeons in an outpatient setting. Patients can usually return home after the procedure.

A computerized axial tomography scan is more commonly known by its abbreviated name, CAT scan or CT scan. It is an x-ray procedure which combines many x-ray images with the aid of a computer to generate cross-sectional views and, if needed, three-dimensional images of the internal organs and structures of the body. A CAT scan is used to define normal and abnormal structures in the body and/or assist in procedures by helping to accurately guide the placement of instruments or treatments. A large donut-shaped x-ray machine takes x-ray images at many different angles around the body. These images are processed by a computer to produce cross-sectional pictures of the body. In each of these pictures the body is seen as an x-ray "slice" of the body, which is recorded on a film. This recorded image is called a tomogram. "Computerized Axial Tomography" refers to the recorded tomogram "sections" at different levels of the body.

Imagine the body as a loaf of bread and you are looking at one end of the loaf. As you remove each slice of bread, you can see the entire surface of that slice from the crust to the center. The body is seen on CAT scan slices in a similar fashion from the skin to the central part of the body being examined. When these levels are further "added" together, a three-dimensional picture of an organ or abnormal body structure can be obtained. CAT scans are performed to analyze the internal structures of various parts of the body. This includes the head, where traumatic injuries, (such as blood clots or skull fractures), tumors, and infections can be identified. In the spine, the bony structure of the vertebrae can be accurately defined, as can the anatomy of the intervertebral discs and spinal cord. In fact, CAT scan methods can be used to accurately measure the density of bone in evaluating osteoporosis.

Occasionally, contrast material (an x-ray dye) is placed into the spinal fluid to further enhance the scan and the various structural relation -ships of the spine, the spinal cord, and its nerves. CAT scans are also used in the chest to identify tumors, cysts, or infections that may be suspected on a chest x-ray. CAT scans of the abdomen are extremely helpful in defining body organ anatomy, including visualizing the liver, gallbladder, pancreas, spleen, aorta, kidneys, uterus, and ovaries. CAT scans in this area are used to verify the presence or absence of tumors, infection, abnormal anatomy, or changes of the body from trauma.

An MRI (or magnetic resonance imaging) scan is a radiology technique which uses magnetism, radio waves, and a computer to produce images of body structures. The MRI scanner is a tube surrounded by a giant circular magnet. The patient is placed on a moveable bed which is inserted into the magnet. The magnet creates a strong magnetic field which aligns the protons of hydrogen atoms, which are then exposed to a beam of radio waves. This spins the various protons of the body, and they produce a faint signal which is detected by the receiver portion of the MRI scanner. The receiver information is processed by a computer, and an image is then produced. The image and resolution produced by MRI is quite detailed and can detect tiny changes of structures within the body. For some procedures, contrast agents such as gadolinium are used to increase the accuracy of the images.

An MRI scan can be used as an extremely accurate method of disease detection throughout the body. In the head, trauma to the brain can be seen as bleeding or swelling. Other abnormalities often found include brain aneurysms, stroke, tumors of the brain, as well as tumors or inflammation of the spine. Neurosurgeons use an MRI scan not only in defining brain anatomy but in evaluating the integrity of the spinal cord after trauma. It is also used when considering problems associated with the vertebrae or intervertebral discs of the spine. An MRI scan can evaluate the structure of the heart and aorta, where it can detect aneurysms or tears. It provides valuable information on glands and organs within the abdomen, and accurate information about the structure of the joints, soft tissues, and bones of the body. Often, surgery can be deferred or more accurately directed after knowing the results of an MRI scan.

An MRI scan is a painless radiology technique which has the advantage of avoiding x-ray radiation exposure. There are no known side effects of an MRI scan. The benefits of an MRI scan relate to its precise accuracy in detecting structural abnormalities of the body. Patients who have any metallic materials within the body must notify their physician prior to the examination or inform the MRI staff. Metallic chips, materials, surgical clips, or foreign material (artificial joints, metallic bone plates, or prosthetic devices, etc.) can significantly distort the images obtained by the MRI scanner. Patients who have heart pacemakers, metal implants, or metal chips or clips in or around the eyeballs cannot be scanned with an MRI because of the risk that the magnet may move the metal in these areas. Similarly, patients with artificial heart valves, metallic ear implants, bullet fragments, and chemotherapy or insulin pumps should not have MRI scanning.

A traditional method of monitoring the joint disease of patients with rheumatoid arthritis is x-rays, whereby images are produced by exposing photographic film (radiographs). This technique has proven useful for doctors to follow the course of joint destruction. The early development of discrete bony destruction (erosions) is associated with more severe rheumatoid disease. While standard x-ray radiographs contribute substantially to the clinical evaluation of rheumatoid arthritis, they do lack some sensitivity early in the course of disease. This means that substantial joint destruction must happen before changes on the standard x-ray test become apparent.

Modern treatment for rheumatoid arthritis is frequently directed at early disease. Accordingly, there efforts to establish methods for early diagnosis of the disease have increased. Several radiographic imaging modalities have been explored including magnetic resonance imaging (MRI) and ultrasonography.

MRI scanning has been found to be sensitive as an indicator of early rheumatoid joint destruction, but it is very expensive and not widely available.

Ultrasonography is an attractive method of imaging because of its low cost, absence of harmful radiation, and rapidity of imaging. Recent advances in ultrasound image technology have allowed the development of sonographic equipment for imaging inflamed joints in patients with rheumatoid arthritis.

In a recent study published in Arthritis and Rheumatism ultrasound imaging was compared with standard x-ray imaging and shown to be superior at detecting bone erosions early in the course of rheumatoid arthritis. In this study, 100 patients with rheumatoid arthritis underwent ultrasound and x-ray imaging of their hands. Twenty control patients were included in the ultrasound (but not x-ray) analysis for comparison. In the group of 100 RA patients, 127 abnormalities were detected in 56 patients by ultrasound, compared with 32 abnormalities in 17 patients detected by x-ray analysis.

When patients with early rheumatoid arthritis were analyzed, 6.5 fold more abnormalities were detected by ultrasonography than by x-ray films. There were erosions detected by x-ray that were missed by ultrasound; the correlation between erosions seen by x-ray and those seen by ultrasound was 86%. From these results, the authors conclude that ultrasound is a reliable technique with greater sensitivity than standard x-ray radiography. They note that the ultrasound technique is influenced and limited by technical performance, requiring appropriate use of the sonographic equipment.

Ultrasound technique and interpretation are both delicate matters. And, for this test to prove out useful, many more studies and standardizations will be required. Other, limitations of this study include the technique used for analysis (only one x-ray view was obtained) and patient selection (patients with severe deformities were excluded.

Overall, these results hold out the potential for a rapid, safe, and sensitive alternative to traditional x-ray analysis of joints in RA patients. We await further studies that will be necessary to correlate ultrasound findings with clinical outcomes in rheumatoid arthritis such as disease progression, joint destruction, and response to therapy.

For now, X-ray testing remains the standard monitoring test for joint destruction (MIR is more costly and facilites are limited in many centres.