ANKYLOSING SPONDYLITIS GENERAL DISCUSSION Ankylosing spondylitis is a progressive inflammatory disease that typically becomes evident during early

to mid adulthood. The disease is characterized by inflammation (arthritis), stiffness, and pain of various joints of the spine and potential loss of spinal mobility. It may involve joints between the spine and the pelvis, known as the sacroiliac joints; joints within the spinal column of the lower back (lumbar spine), the upper back (thoracic spine), and the neck (cervical spine) to varying degrees; as well as joints of the limbs, particularly the legs. Progression may spontaneously subside at any stage of involvement; however, in some individuals, all regions of the spinal column may eventually become involved. Many affected individuals develop lower back and hip pain that may be more severe at night and after rest. In addition, there is often associated stiffness of affected regions in the morning. In some cases, those with involvement of joints joining the ribs with the spine (costovertebral joints) may have a limited ability to expand the chest to take a deep breath. In addition, in some affected individuals, other associated findings may include recurrent inflammation of the colored region of the eyes (acute iritis), leakage of the aortic valve resulting in a backflow of blood into the lower left chamber (ventricle) of the heart (aortic insufficiency or regurgitation), and/or other abnormalities. The exact cause of ankylosing spondylitis is not known. However, researchers suggest that genetic, immunologic, and/or environmental factors may play some role. SYMPTOMS The most common symptoms of ankylosing spondylitis include back pain and abnormal postures in response to the inflamed (arthritic) vertebrae in the spine. Pain is frequently worse after periods of rest and at night, and may be associated with morning stiffness. Pain typically improves with exercise and the application of heat. Early in the course of ankylosing spondylitis, symptoms may include muscle spasms in the back that inhibit normal motion of the spine during bending (flexion). Eventually, immobility of the vertebrae may also limit the motion of the spine. In advanced disease ankylosing spondylitis may result in immobility or fusion (ankylosis) of the entire spine, resulting in a straight or "poker" spine. Symptoms of ankylosing spondylitis may involve joints outside the spinal area (peripheral), especially the hips and shoulders, which are the first affected joints in 20 percent of cases. Neck movement may also be limited in some people with this disorder. About 30 percent of people with ankylosing spondylitis develop inflammation of the

iris of the eyes (iritis) which is characterized by pain, excessive tearing (lacrimation), extreme sensitivity to light (photophobia), and/or visual impairment. Breathing capacity may be diminished and the chest may become fixed due to immobility of the rib cage (costovertebral joints). Neurological complications of ankylosing spondylitis may include the inability to control urination and defecation (incontinence) and the absence of normal reflexes in the ankles (ankle jerks) due to pressure on the lower portion of the spinal cord (cauda equina). In fewer than 10 percent of people with ankylosing spondylitis, the function of the heart may also be impaired including interference with the normal electrical impulses of the heart (heartblock), irregular heartbeat (arrhythmia), and/or aortic insufficiency after longstanding disease. CAUSES The specific underlying cause of ankylosing spondylitis is unknown. However, investigators indicate that over 90 percent of individuals with the disorder have a particular, genetically determined HLA, or "human leukocyte antigen," known as HLAB27. HLAs are proteins that play an important role in the body's immune system. The possible role that HLA-B27 may play in genetically predisposing individuals to ankylosing spondylitis remains unknown. The genes that determine and regulate production of such proteins (major histocompatibility complex [MHC]) have been mapped to a region on the short arm (p) of chromosome 6 (6p21.3). Researchers suggest that certain genes on other chromosomes may also possibly be a factor in genetically predisposing to ankylosing spondylitis in some cases. Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q." Chromosomes are further subdivided into bands that are numbered. Therefore, for example, 6p21.3 refers to band 21.3 on the short arm of chromosome 6. Some investigators suggest that ankylosing spondylitis may follow exposure to certain intestinal (enteric) bacteria, leading to an abnormal immune reaction directed against the body's own tissues (autoimmune response) in genetically predisposed individuals. Tests have indicated that many affected individuals have increased levels of antibodies in the blood directed against particular enteric bacteria, such as the bacterium Klebsiella pneumoniae. Further research is needed to learn more about the underlying genetic, immunologic, and/or other mechanisms that may result in ankylosing spondylitis.

AFFECTED POPULATIONS Ankylosing spondylitis is a rare disorder that affects at least 3 times more males than females. The symptoms usually begin between the ages of 20 and 40 years. Ankylosing spondylitis occurs more frequently among Americans of European descent than Americans of African descent who typically experience milder symptoms. In the US about 1.4% of the population is affected by this condition. RELATED DISORDERS Symptoms of the following disorders can be similar to those of ankylosing spondylitis. Comparisons may be useful for a differential diagnosis: Rheumatoid arthritis (RA) is a chronic progressive form of arthritis that eventually leads to the destruction of the bone joints causing pain and physical deformity. Rheumatoid arthritis is characterized by joint (arthritis) inflammation on both sides of the body (symmetrical) leading to swelling, pain, and decreased mobility. The symptoms of this disease usually appear during middle age and it is most common in females. The course of the disease is highly variable and may include episodes of remission. Reiter's syndrome is a rare disorder characterized by arthritis, inflammation of the urinary tract (nongonococcal urethritis), and inflammation of the mucous membranes that line the eyelids (conjunctivitis). Painful and swollen joints occur because of an underlying infection (reactive arthritis). Sores (lesions) may also occur in the skin and the mucous membranes of the mouth. In most cases, Reiter's syndrome in transmitted through sexual contact (venereal). Other symptoms include warm, red, swollen, and painful joints. The major joints of the legs and feet are most frequently effected. However, the spine may also be involved. (For more information on this disorder, choose "Reiter" as your search term in the Rare Disease Database.) Psoriatic arthritis is an arthritic condition that is associated with psoriasis of the skin and/or nails and a negative test for the rheumatoid factor (RF). The characteristic symptoms are inflammation of the joints and surrounding tissues accompanied by psoriasis of the nails and psoriatic plaques on the scalp, elbows, knees, and lower spine. Psoriasis usually precedes joint involvement in over 80 percent of cases. The symptoms of psoriasis include red, silvery-gray, sharply outlined spots or plaques that usually appear on the scalp, behind the ears, and/or on the elbows and knees. In the classical form of the disease, involvement is limited to the joints of the hands and feet. In the other forms, arthritis may extend to many other joints of the body, including the spine. (For more information on this disorder, choose "Psoriatic Arthritis" as your search term in the Rare Disease Database.) Infective arthritis is an arthritic condition that occurs as a result of infection of tissues of one or more joints by bacteria, viruses, or fungi. The symptoms vary greatly and

depend on the infectious agent. Symptoms may include fever, chills, general weakness, and/or headaches, followed by inflammation of one or more joints. Within a few hours or days, the affected joint or joints often become very painful, swollen, slightly red and stiff. Rapid onset of symptoms may indicate that a bacterium is the cause. Viral or fungal agents tend to cause a more slowly progressive form of the disease. (For more information on this disorder, choose "Infective Arthritis" as your search term in the Rare Disease Database.) Osteoarthritis is the most common form of arthritis characterized by degenerative changes in the joints and inflammation of the membranes that line the fluid-filled spaces around joints. The exact cause of osteoarthritis is not known although chemical, genetic, metabolic, and endocrine factors have been implicated. Stress may aggravate this condition. The symptoms may include joint pain after exercise, stiffness, tenderness, and/or swelling. Involvement of the knees, hips, and/or spine may cause difficulty walking. STANDARD THERAPIES Treatment Treatment of ankylosing spondylitis is aimed at reducing inflammation in the joints and maintaining flexibility. Most people with ankylosing spondylitis respond well to medications that help reduce pain and inflammation, along with exercises that improve posture and strengthen muscle groups. The U.S. Food and Drug Administration (FDA) has approved infliximab (Remicade) for the treatment of symptoms, such as spinal pain, of ankylosing spondylitis. This drug is produced by Centocor, Inc., of Malvern, Pa. For information, go to www.remicade.com. Amgen/Wyeth received approval from the U.S. Food and Drug Administration (June 2003) to include ankylosing spondylitis among the indications for the use of the biotech drug etanercept (Enbrel). To date (2004), it is the first and only biologic approved as a treatment for ankylosing spondylitis. Exercises may be prescribed under a doctor's supervision stressing back movements, deep breathing, straightening of the chest portion of the spine, deep-bending exercises, and a full range of motion of the spine in all directions. Bending (flexion) postures should not be maintained for long periods of time. To avoid flexion of the neck and upper back, affected individuals should sleep on their backs with a firm mattress and use no pillow or a very flat pillow. The chest muscles can be stretched and the upper back straightened by locking the fingers behind the head and pushing the elbows as far back as possible. Swimming is also excellent exercise for people with this disorder. Prior to exercise, hot baths or warm showers may be helpful to relax muscles and to attain better range of motion. People with ankylosing spondylitis should have ample rest each day and avoid exhaustion.

These exercises and physical therapy can be administered immediately upon diagnosis to retain as normal an upright posture as possible and reduce the potential for physical deformity. This is particularly important for people who are diagnosed early in life. Nonsteroidal anti-inflammatory drugs (NSAIDs) or other painkillers such as naproxen, sulindac, diclofenac or phenylbutazone may help to relieve pain, permitting better sleep and increasing the ability to exercise. Narcotics and systemic corticosteroids are usually avoided. Some people with ankylosing spondylitis may benefit from the use of a back brace, but it is frequently unnecessary. Therapeutic measures often eliminate the need for surgery to straighten the spine. However, in rare cases, if the above treatments are not successful, surgery may be performed to straighten the spine. INVESTIGATIONAL THERAPIES Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website. For information about clinical trials sponsored by private sources, contact: www.centerwatch.com There are five trials listed on the NIH site that involve ankylosing spondylitis. One of them is an investigation of the drug, adalimumab (HUMIRA), manufactured by Abbott Laboratories. A phase III trial was launched in April 2004 to determine its effectiveness in treating ankylosing spondylitis. Patients are being recruited for several testing locations across 16 states. For information, use the NIH sources listed above or contact: There are three trials evaluating various aspects of genetics and one trial assessing the best testing methods for spinal fusion and other symptoms of ankylosing spondylitis. All of them are presently (2004) recruiting volunteers. For information, use the NIH tollfree phone number or the Clinical Trials web site listed above. Sulfasalazine has been tested for the treatment of seronegative spondyloarthropathies. The drug is found to be helpful in arthritis symptoms of ankylosing spondylitis but has little effect on spinal pain and general treatment of the disease. More studies are needed to determine the long-term safety and effectiveness of this treatment. The protein molecule HLA-B27, known to be a genetic marker for ankylosing spondylitis and some forms of arthritis, has aided researchers in developing an animal model for the disease. This will be a great help in understanding the cause and progression of this disorder, and testing new treatments for arthritis and ankylosing spondylitis. In 1999, The National Institute of Arthritis and Musculoskeletal and Skin

Diseases (NIAMS) awarded $4.5 million to establish the North American Spondylitis Consortium to identify genes that determine susceptibility to ankylosing spondylitis. John D. Reveille, M.D. at the University of Texas-Houston Health Science Center, coordinates this work. Affected individuals and physicians interested in participating in the study should contact:

About Ankylosing Spondylitis (AS) Ankylosing spondylitis (AS) is a disease that can cause pain and inflammation of the joints of the spine. AS usually affects the joints between the vertebrae and almost always the sacroiliac joints (the area where your spine meets your pelvis). It also causes inflammation at the spot where the tendons and ligaments join the bone. In many people, joints of the arms and legs can also be affected. If left untreated, it eventually can cause the affected spinal bones to fuse together. Early diagnosis and treatment helps manage symptoms and may help to limit damage to the spine and damage to other joints. A few of the joints typically affected by AS

Ankylosing spondylitis can affect the joints between the vertebrae, the sacroiliac joints (the area where your spine meets your pelvis), hips, and shoulders, as well as other joints.

What causes AS? The cause of ankylosing spondylitis is unknown, but AS is thought to be a disease of the immune system. The immune system protects the body from infections and diseases. It is believed that, among a number of changes in the immune system, there are increased levels of an active form of a protein called tumor necrosis factor (TNF) that plays a role in the inflammation associated with AS. Genetic factors seem to contribute to the risk of developing ankylosing spondylitis. People who have a gene called HLA-B27 are at an increased risk of developing the condition. Additionally, certain infections may also be related. Symptoms of AS Typical symptoms of ankylosing spondylitis include lower back pain and stiffness. These symptoms may improve after movement, exercise, or a hot shower. Other symptoms include pain and swelling in neck, hips, knees, or ankles; difficulty expanding the chest; and fatigue. Other parts of the body can also be affected. Ankylosing spondylitis can get worse over time. Getting help from a doctor as soon as possible is important. The natural progression of AS involves stiffening of the spine over time, with fusion of all or some of the spinal joints occurring after some years of disease in about two thirds of patients. Treating AS There is no cure for ankylosing spondylitis, but many treatments can help. Many people start with over-the-counter drugs and prescription pain relievers and anti-inflammatory drugs. Your doctor may also prescribe an individualized exercise program. These treatments can help manage symptoms of AS, like pain. Your doctor may also try other medications that work on the immune system to treat inflammation and manage symptoms. In many patients, the biologic medicine ENBREL can help manage symptoms associated with AS. Read about results with ENBREL. ENBREL is a prescription medicine that is self-injected. Because ENBREL works on your immune system, it may lower your ability to fight infections and may raise other safety concerns. If you have any sign of an infection including a fever, cough, flu-like symptoms, or have any open sores on your body, call your doctor. Please see Prescribing Information,Important Safety Information, and Medication Guide for complete details about ENBREL.

What Is ENBREL?
ENBREL is a prescription medicine that can be self-injected. It is used to treat five longterm inflammatory diseases: moderate to severe rheumatoid arthritis (RA), adult chronic moderate to severe plaque psoriasis in patients who are candidates for systemic therapy or phototherapy, psoriatic arthritis, moderate to severe juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). ENBREL is grouped within a class of medications called biologic response modifiers, or biologics. By working on the immune system, biologics block proteins that contribute to the disease process. Because ENBREL suppresses the immune system, patients are at a greater risk for getting serious infections. The science behind ENBREL Tumor necrosis factor (TNF) is a substance made by your body's immune system. People with inflammatory diseases such as rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, juvenile idiopathic arthritis, and ankylosing spondylitis have too much TNF in their bodies. ENBREL reduces levels of the active form of TNF. The clinical history of ENBREL first biologic approved for moderate to severe rheumatoid arthritis established safety profile over 10 years of continuous safety data in patients with moderate to severe rheumatoid arthritis

Prescription ENBREL is taken by injection. IMPORTANT SAFETY INFORMATION INDICATIONS Moderate to Severe Rheumatoid Arthritis (RA) ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse, and improving physical function in patients with moderate to severe rheumatoid arthritis. ENBREL can be taken with methotrexate or used alone. Moderately to Severely Active Polyarticular Juvenile Idiopathic Arthritis (JIA) ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in children ages 2 years and older. Psoriatic Arthritis ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse, and improving physical function in patients with psoriatic arthritis. ENBREL can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone. Ankylosing Spondylitis (AS) ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis. Moderate to Severe Plaque Psoriasis ENBREL is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Supportive data Moderate to Severe Rheumatoid Arthritis (RA)

In medical studies, ENBREL was shown to be clinically effective in about 2 out of 3 adults with moderate to severe RA at 3 months. ENBREL has been shown to begin working in as few as 2 weeks, and most patients who benefit will do so within 3 months. In another medical study, 55% of patients who were evaluated 5 years after beginning ENBREL therapy had no further progression of joint damage. Moderately to Severely Active Polyarticular Juvenile Idiopathic Arthritis (JIA) In a clinical study, ENBREL was shown to be effective in about 3 out of 4 children with JIA who used it at 3 months. ENBREL has been shown to begin working in as few as 2 to 4 weeks. Psoriatic Arthritis ENBREL was shown to be effective in about 50% of patients at 6 months. Clinical responses were apparent at the time of the first visit (4 weeks) and were maintained through 6 months of therapy. Ankylosing Spondylitis (AS) ENBREL was shown to be effective in about 3 out of 5 adults at 6 months. Clinical responses were seen at 2 weeks in 46% of patients, with 59% of patients receiving benefit within 8 weeks. Moderate to Severe Plaque Psoriasis In medical studies, nearly half of patients saw 75% skin clearance in 3 months. Overall, 3 out of 4 patients saw 50% skin clearance in 3 months.

IMPORTANT SAFETY INFORMATION Only your doctor can recommend a course of treatment after checking your health condition. REMICADE (infliximab) can cause serious side effects such as lowering your ability to fight infections.Some patients, especially those 65 years and older, have had serious infections caused by viruses, fungi or bacteria that have spread throughout the body, including tuberculosis (TB) and histoplasmosis. Some of these infections have been fatal. Your doctor should monitor you closely for signs and symptoms of TB during treatment with REMICADE. Unusual cancers have been reported in children and teenage patients taking TNFblocker medicines. Hepatosplenic T-cell lymphoma, a rare form of fatal lymphoma, has occurred mostly in teenage or young adult males with Crohns disease or ulcerative colitis who were taking REMICADE and azathioprine or 6-mercaptopurine. For children and adults taking TNF blockers, including REMICADE, the chances of getting lymphoma or other cancers may increase. You should discuss any concerns about your health and medical care with your doctor. What should I tell my doctor before I take REMICADE? You should let your doctor know if you have or ever had any of the following: Tuberculosis (TB) or have been near someone who has TB. Your doctor will check you for TB with a skin test. If you have latent (inactive) TB, you will begin TB treatment before you start REMICADE. Lived in a region where certain fungal infections like histoplasmosis or coccidioidomycosis are common. Infections that keep coming back, have diabetes or an immune system problem. Any type of cancer or a risk factor for developing cancer, for example, chronic obstructive pulmonary disease (COPD) or had phototherapy for psoriasis. Heart failure or any heart condition. Many people with heart failure should not take REMICADE. Hepatitis B virus (HBV) infection or think you may be a carrier of HBV. Your doctor will test you for HBV.

Nervous system disorders (like multiple sclerosis or Guillain-Barr syndrome). Also tell your doctor if you: Use the medicines Kineret (anakinra), Orencia (abatacept) or Actemra (tocilizumab) or other medicines called biologics used to treat the same problems as REMICADE. Are pregnant, plan to become pregnant, are breast-feeding, or have a baby and were using REMICADE during your pregnancy. Tell your babys doctor about your REMICADE use before the baby receives any vaccine because of an increased risk of infection for up to 6 months after your last dose of REMICADE you received during your pregnancy. Adults and children should not receive a live vaccine while taking REMICADE. What should I watch for and talk to my doctor about before or while taking REMICADE? The following serious (sometimes fatal) side effects have been reported in people taking REMICADE. You should tell your doctor right away if you have any of the signs listed below: Infections (like TB, blood infections, pneumonia)fever, tiredness, cough, flu, or warm, red or painful skin or any open sores. REMICADE can make you more likely to get an infection or make any infection that you have worse. Lymphoma, or any other cancers in adults and children. Skin cancerany changes in or growths on your skin. Heart failurenew or worsening symptoms, such as shortness of breath, swelling of your ankles or feet, or sudden weight gain. Reactivation of HBVfeeling unwell, poor appetite, tiredness, fever, skin rash and/or joint pain. Liver injuryjaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe tiredness. Blood disordersfever that doesnt go away, bruising, bleeding or severe paleness. Nervous system disordersnumbness, weakness, tingling, changes in your vision or seizures. Allergic reactions during or after the infusionhives, difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, and fever or chills. Lupus-like syndromechest discomfort or pain that does not go away, shortness of breath, joint pain, rash on the cheeks or arms that gets worse in the sun. The more common side effects with REMICADE are respiratory infections (that may include sinus infections and sore throat), headache, rash, coughing and stomach pain. Psoriasisnew or worsening psoriasis such as red scaly patches or raised bumps on the skin that are filled with pus.

Function

Remicade Infliximab is a biomedicine or biologic. It is used to treat symptoms of the autoimmune diseases plaque psoriasis, rheumatoid arthritis, psoriatic arthritis, adult and pediatric crohn's disease, ulcerative colitis and ankylosing spondylitis. These diseases cause the immune system to go into a sort of overdrive. The immune system attacks the healthy body tissue and causes inflammation. If untreated the disease influenced immune system will permanently damage the body's bones, tissue and cartilage. The diseased body has an overabundance of tumor necrosis factor alpha (TNF). TNF alpha is a protein which is made by select red blood cells. When it is blocked by Remicade the inflammation may be reduced giving the patient relief from painful and sometimes debilitating symptoms for a period of time. Considerations

Remicade is a biologic, a product made from a living thing and sometimes made in a living thing. Remicade is made with the aid of mice. It was developed and is distributed by Centocor, a research and biomanufacturer which is owned by Johnson & Johnson. It is administered in a doctor's office or hospital treatment room. A patient is settled into a lounge chair. First an over-the-counter pain pill and allergy tablet is given to the patient. The administering nurse will check for fever and set the patient up with a blood pressure monitor. The biomedication is given through intravenous. This is a form of chemotherapy. The patient can expect to be in the treatment room for 3 hours on an average. The first treatment can take four hours as it is given very slowly while reaction possibilities are monitored closely. The patient is made as comfortable as possible.The nurse sees to it that the patient has a drink, snacks and explains how the IV can be moved if there is a need to go to the restroom. It is very important that the patient stays hydrated. Sponsored Links QuickBooks From Intuit Intuit QuickBooks is now in India. A Must Software for SMEs. Try Free! quickbooks.in Benefits

Once a patient has the first two treatments a few weeks apart he or she will soon be switched to one treatment every 8 weeks. Each patient will react differently. Relief from symptoms can show up by the third or fourth treatment. Pain may decrease, inflammation subside and those with gastrointestinal distress may find that her appetite is picking up with less frequent trips to the bathroom. Remicade has given patients back some quality of life. Warning

A patient has increased risk for infection with Remicade treatments. A TB test must be done to determine if a patient has tuberculosis present in their body. Remicade can not be administered if there is any serious infection is in the patients system. An infection could easily spread through the body resulting in hospitalization. A patient could die

from this infection. When undergoing Remicade treatments a patient must pay strict attention to any signs of infection especially one that involves the lungs. Fever, extreme tiredness, a cough, flu like symptoms, warm red or painful skin are all signs to report to your Remicade nurse, physicians' assistant, doctor or gastroenterologist right away. The patient must be aware that there are possible side affects to look for from sore throat, fever, headache and rashes. One major issue is a rare and deadly liver failure which was announced in December of 2004. Potential

Remicade treatments are an intense way for a autoimmune disease patient to gain a form of relief from intense pain, loss of a social life, failing health and even the ability to move or eat. It is a major decision to make because it can affect the rest of the patient's life. There is no cure for autoimmune diseases. Remicade has mild to serious side affects including lymphoma cancer. It is very helpful for the patient to be well informed as the decision is made. There are many pros and cons to be weighed.

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