ARTHRITIS

Arthritis is a joint disorder featuring inflammation. A joint is an area of the body where two different bones meet. A joint functions to move the body parts connected by its bones. Arthritis literally means inflammation of one or more joints. Arthritis is frequently accompanied by joint pain. Joint pain is referred to as arthralgia. There are many types of arthritis (over 100 identified, and the number is growing). The types range from those related to wear and tear of cartilage (such asosteoarthritis) to those associated with inflammation resulting from an overactive immune system (such asrheumatoid arthritis). Together, the many types of arthritis make up the most common chronic illness in the United States. The causes of arthritis depend on the form of arthritis. Causes include injury (leading to osteoarthritis), metabolic abnormalities (such as gout andpseudogout), hereditary factors, the direct and indirect effect of infections (bacterial and viral), and a misdirected immune system with autoimmunity (such as in rheumatoid arthritis andsystemic lupus erythematosus). Arthritis is classified as one of the rheumatic diseases. These are conditions that are different individual illnesses, with differing features, treatments, complications, and prognoses. They are similar in that they have a tendency to affect the joints, muscles, ligaments, cartilage, and tendons, and many have the potential to affect other internal body areas.

OSTEOARTHRITIS Overview Osteoarthritis is a form of arthritis that features the breakdown and eventual loss of the cartilage of one or more joints. Cartilage is a protein substance that serves as a "cushion" between the bones of the joints. Among the over 100 different types of arthritis conditions, osteoarthritis is the most common, affecting over 25 million people in the United States. Osteoarthritis occurs more frequently as we age. Before age 45, osteoarthritis occurs more frequently in males. After 55 years of age, it occurs more frequently in females. In the United States, all races appear equally affected. A higher incidence of osteoarthritis exists in the Japanese population, while South-African blacks, East Indians, and Southern Chinese have lower rates. Osteoarthritis is abbreviated as OA or referred to as degenerative arthritis or degenerative joint disease (DJD). Osteoarthritis commonly affects the hands, feet, spine, and large weight-bearing joints, such as the hips and knees. Osteoarthritis usually has no known cause and is referred to as primary osteoarthritis. When the cause of the osteoarthritis is known, the condition is referred to as secondary osteoarthritis.

Causes Primary osteoarthritis, osteoarthritis not resulting from injury or disease, is mostly a result of natural aging of the joint. With aging, the water content of the cartilage increases, and the protein makeup of cartilage degenerates. Eventually, cartilage begins to degenerate by flaking or forming tiny crevasses. In advanced osteoarthritis, there is a total loss of the cartilage cushion between the bones of the joints. Repetitive use of the worn joints over the years can irritate and inflame the cartilage, causing joint pain and swelling. Loss of the cartilage cushion causes friction between the bones, leading to pain and limitation of joint mobility. Inflammation of the cartilage can also stimulate new bone outgrowths (spurs, also referred to as osteophytes) to form around the joints. Osteoarthritis occasionally can develop in multiple members of the same family, implying a hereditary (genetic) basis for this condition.

Secondary osteoarthritis is a form of osteoarthritis that is caused by another disease or condition. Conditions that can lead to secondary osteoarthritis include obesity, repeated trauma or surgery to the joint structures, abnormal joints at birth (congenital abnormalities), gout, diabetes, and other hormone disorders. Obesity causes osteoarthritis by increasing the mechanical stress on the joint and therefore on the cartilage. In fact, next to aging, obesity is the most significant risk factor for osteoarthritis of the knees. The early development of osteoarthritis of the knees among weight lifters is believed to be in part due to their high body weight. Repeated trauma to joint tissues (ligaments, bones, and cartilage) is believed to lead to early osteoarthritis of the knees in soccer players and army military personnel. Interestingly, studies have not found an increased risk of osteoarthritis in long-distance runners. Crystal deposits in the cartilage can cause cartilage degeneration and osteoarthritis. Uric acid crystals cause arthritis in gout, while calcium pyrophosphate crystals cause arthritis in pseudogout. Some people are born with abnormally formed joints (congenital abnormalities) that are vulnerable to mechanical wear, causing early degeneration and loss of joint

cartilage. Osteoarthritis of the hip joints is commonly related to structural abnormalities of these joints that had been present since birth. Hormone disturbances, such as diabetes and growth hormone disorders, are also associated with early cartilage wear and secondary osteoarthritis.

Pathophysiology The main cause of Osteoarthritis is an imbalance in the natural breakdown and repair process that occurs with cartilage. In Osteoarthritis, damaged cartilage cannot repair itself in the normal way. It occurs when the cartilage that covers and cushions the ends of bones in your joints deteriorates over time. Cartilage is composed of water, collagen, and specific proteins. In healthy cartilage, there is a continual process of natural breaking down and repair of the cartilage in joints. This process becomes disrupted in Osteoarthritis, leading to cartilage deterioration and an abnormal repair response. The reason this normal repair process is disrupted is not known but it is likely caused by several factors. With aging, the water content of the cartilage increases, and the protein makeup of cartilage breaks down. Eventually, the smooth surface of the cartilage begins to deteriorate and become worn causing friction between the bones. If the cartilage wears down completely, the result will be bone to bone contact. Repetitive use of worn joints over the years can irritate the cartilage, causing joint pain and inflammation of surrounding tissues. As pieces of cartilage break off, the bones thicken and broaden, causing inflammation. This inflammation may stimulate new bone outgrowths called spurs (also called osteophytes) to form around the joints. As the bones thicken and broaden, joints become stiff, painful, and may be difficult to move. Fluid may also build up in your joints. Manifestations The most common symptom of osteoarthritis is pain in the affected joint(s) after repetitive use. Joint pain of osteoarthritis is usually worse later in the day. There can be

swelling, warmth, and creaking of the affected joints. Pain and stiffness of the joints can also occur after long periods of inactivity (for example, sitting in a theater). In severe osteoarthritis, complete loss of the cartilage cushion causes friction between bones, causing pain even at rest or pain with limited motion. Symptoms of osteoarthritis vary greatly from patient to patient. Some patients can be debilitated by their symptoms. On the other hand, others may have remarkably few symptoms in spite of dramatic degeneration of the joints apparent on X-rays. Symptoms also can be intermittent. It is not unusual for patients with osteoarthritis of the finger joints of the hands and knees to have years of pain-free intervals between symptoms. Osteoarthritis of the knees is often associated with excess upper body weight, with obesity, or a history of repeated injury and/or joint surgery. Progressive cartilage degeneration of the knee joints can lead to deformity and outward curvature of the knees, which is referred to as being "bowlegged." People with osteoarthritis of the weight-bearing joints (such as the knees) can develop a limp. The limping can worsen as more cartilage degenerates. In some patients, the pain, limping, and joint dysfunction may not respond to medications or other conservative measures. Therefore, severe osteoarthritis of the knees is one of the most common reasons fortotal knee replacement surgical procedures in the United States. Osteoarthritis of the cervical spine or lumbar spine causes pain in the neck or low back. Bony spurs, called osteophytes, that form along the arthritic spine can irritate spinal nerves, causing severe pain that can radiate from the spine as well as numbness and tingling of the affected parts of the body. Osteoarthritis causes the formation of hard, bony enlargements of the small joints of the fingers. Classic bony enlargement of the small joint at the end of the fingers is called a Heberden's node, named after a famous British doctor. The bony deformity is a result of the bone spurs from the osteoarthritis in that joint. Another common bony knob (node) occurs at the middle joint of the fingers in many patients with osteoarthritis and is called a Bouchard's node. Dr. Bouchard was a famous French doctor who also studied arthritis patients in the late 1800s. Heberden's and Bouchard's nodes may not be painful, but they are often associated with limitation of motion of the joint. The characteristic appearances of these finger nodes can be helpful in diagnosing osteoarthritis. Osteoarthritis of the joint at the base of the big toe of the foot leads to the formation of a bunion. Osteoarthritis of the fingers and the toes may have a genetic basis and can be found in numerous female members of some families.

Diagnostic Procedures There is no blood test for the diagnosis of osteoarthritis. Blood tests are performed to exclude diseases that can cause secondary osteoarthritis, as well as to exclude other arthritis conditions that can mimic osteoarthritis. X-rays of the affected joints can be used to diagnose osteoarthritis. The common X-ray findings of osteoarthritis include loss of joint cartilage, narrowing of the joint space

between adjacent bones, and bone spur formation. Simple X-ray testing can also be very helpful to exclude other causes of pain in a particular joint as well as assisting the decision-making as to when surgical intervention might be considered. Arthrocentesis is a procedure to remove joint fluid that is often performed in the doctor's office. During arthrocentesis, a sterile needle is used to remove joint fluid for analysis. Joint fluid analysis is useful in excluding gout, infection, and other causes of arthritis. Removal of joint fluid and injection of corticosteroids into the joints during arthrocentesis can help relieve pain, swelling, and inflammation. Arthroscopy is a surgical technique whereby a doctor inserts a viewing tube into the joint space. Abnormalities of and damage to the cartilage and ligaments can be detected and sometimes repaired through the arthroscope. If successful, patients can recover from the arthroscopic surgery much more quickly than from open joint surgery. Finally, a careful analysis of the location, duration, and character of the joint symptoms and the appearance of the joints helps the doctor in diagnosing osteoarthritis. Bony enlargement of the joints from spur formations is characteristic of osteoarthritis. Therefore, the presence of Heberden's nodes, Bouchard's nodes, and bunions of the feet can indicate to the doctor a diagnosis of osteoarthritis.

Medical Management Aside from weight reduction and avoiding activities that exert excessive stress on the joint cartilage, there is no specific treatment to halt cartilage degeneration or to repair damaged cartilage in osteoarthritis. The goal of treatment in osteoarthritis is to reduce joint pain and inflammation while improving and maintaining joint function. Some patients with osteoarthritis have minimal or no pain and may not need treatment. Others may benefit from conservative measures such as rest,exercise, diet control with weight reduction, physical therapy and/or occupational therapy, and mechanical support devices, such as knee braces. These measures are particularly important when large, weight-bearing joints are involved, such as the hips or knees. In fact, even modest weight reduction can help to decrease symptoms of osteoarthritis of the large joints, such as the knees and hips. Medications are used to complement the physical measures described above. Medication may be used topically, taken orally, or injected into the joints to decrease joint inflammation and pain. When conservative measures fail to control pain and improve joint function, surgery can be considered. Resting sore joints decreases stress on the joints and relieves pain and swelling. Patients are asked to simply decrease the intensity and/or frequency of the activities that consistently cause joint pain. Exercise usually does not aggravate osteoarthritis when performed at levels that do not cause joint pain. Exercise is helpful for relief of symptoms of osteoarthritis in several ways, including strengthening the muscular support around the joints. It also prevents the joints from "freezing up" and improves and maintains joint mobility. Finally, it helps with weight reduction and promotes endurance. Applying local heat before and cold packs after exercise can help relieve pain and inflammation. Swimming is

particularly well suited for patients with osteoarthritis because it allows patients to exercise with minimal impact stress to the joints. Other popular exercises include walking, stationary cycling, and light weight training. Physical therapists can provide support devices, such as splints, canes, walkers, and braces. These devices can be helpful in reducing stress on the joints. Occupational therapists can assess the demands of daily activities and suggest additional devices that may help people at work or home. Finger splints can support individual joints of the fingers. Paraffin wax dips, warm water soaks, and nighttime cotton gloves can help ease hand symptoms. Spine symptoms can improve with a neck collar, lumbar corset, or a firm mattress, depending on what areas are involved.

Pharmacological Management In many patients with osteoarthritis, mild pain relievers such as aspirin and acetaminophen (Tylenol) may be sufficient treatment. Studies have shown that acetaminophen given in adequate doses can often be equally as effective as prescription anti-inflammatory medications in relieving pain in osteoarthritis of the knees. Since acetaminophen has fewer gastrointestinalside effects than NSAIDS (see below), especially among elderly people, acetaminophen is generally the preferred initial drug given to patients with osteoarthritis. Medicine to relax muscles in spasm might also be given temporarily. Pain-relieving creams applied to the skin over the joints can provide relief of minor arthritis pain. Examples include capsaicin (ArthriCare, Zostrix), salycin (Aspercreme), methyl salicylate (BenGay, Icy Hot), and menthol (Flexall). New topical treatments include an anti-inflammatory lotion, diclofenac (Voltaren Gel) and diclofenac patch (Flector Patch), which are used for the relief of the pain of osteoarthritis. No steroidal anti-inflammatory drugs (NSAIDs) are medications that are used to reduce pain and inflammation in the joints. Examples of NSAIDs include aspirin (Ecotrin), ibuprofen (Motrin), nabumetone (Relafen), and naproxen (Naprosyn). It is sometimes possible to use NSAIDs temporarily and then discontinue them for periods of time without recurrent symptoms, thereby decreasing the risk of side effects. The most common side effects of NSAIDs involve gastrointestinal distress, such as stomach upset, cramping diarrhea, ulcers, and even bleeding. The risk of these and other side effects increases in the elderly. Newer NSAIDs called COX-2 inhibitors have been designed that have less toxicity to the stomach and bowels. Because osteoarthritis symptoms vary and can be intermittent, these medicines might be given only when joint pains occur or prior to activities that have traditionally brought on symptoms. Surgical Management

Surgery is generally reserved for those patients with osteoarthritis that is particularly severe and unresponsive to the conservative treatments. Arthroscopy, discussed above, can be helpful when cartilage tears are suspected. Osteotomy is a bone-removal procedure that can help realign some of the deformity in selected patients, usually those with certain forms of knee disease. In some cases, severely degenerated joints are best treated by fusion (arthrodesis) or replacement with an artificial joint (arthroplasty). Total hip and total knee replacements are now commonly performed in community hospitals throughout the United States. These can bring dramatic pain relief and improved function.

GOUTY ARTHRITIS Overview Gout is a disease that results from an overload of uric acid in the body. This overload of uric acid leads to the formation of tiny crystals of urate that deposit in tissues of the body, especially the joints. When crystals form in the joints, it causes recurring attacks of joint inflammation (arthritis). Gout is considered a chronic and progressive disease. Chronic gout can also lead to deposits of hard lumps of uric acid in the tissues, particularly in and around the joints and may cause joint destruction, decreased kidney function, andkidney stones (nephrolithiasis). Gout has the unique distinction of being one of the most frequently recorded medical illnesses throughout history. It is often related to an inherited abnormality in the body's ability to process uric acid. Uric acid is a breakdown product of purines that are part of many foods we eat. An abnormality in handling uric acid can cause attacks of painful arthritis (gout attack), kidney stones, and blockage of the kidney-filtering tubules with uric acid crystals, leading tokidney failure. On the other hand, some people may only develop elevated blood uric acid levels (hyperuricemia) without having manifestations of gout, such as arthritis or kidney problems. The state of elevated levels of uric acid in the blood without symptoms is referred to as asymptomatic hyperuricemia. Asymptomatic hyperuricemia is considered a precursor state to the development of gout. The

term gout refers the disease that is caused by an overload of uric acid in the body, resulting in painful arthritic attacks and deposits of lumps of uric acid crystals in body tissues. Gouty arthritis is typically an extremely painful attack with a rapid onset of joint inflammation. The joint inflammation is precipitated by deposits of uric acid crystals in the joint fluid (synovial fluid) and joint lining (synovial lining). Intense joint inflammation occurs as the immune system reacts, causing white blood cells to engulf the uric acid crystals and chemical messengers of inflammation to be released, leading to pain, heat, and redness of the joint tissues. As gout progresses, the attacks of gouty arthritis typically occur more frequently and often in additional joints Causes and Risk Factors In addition to an inherited abnormality in handling uric acid, other risk factors for developing gout include obesity, excessiveweight gain (especially in youth), moderate to heavy alcohol intake, high blood pressure, and abnormal kidney function. Certain drugs, such as thiazide diuretics (hydrochlorothiazide [Dyazide]), lowdoseaspirin, niacin, cyclosporine, tuberculosismedications (pyrazinamide andethambutol), and others can also cause elevated uric acid levels in the blood and lead to gout. Furthermore, certain diseases lead to excessive production of uric acid in the body. Examples of these diseases include leukemias, lymphomas, andhemoglobin disorders. Interestingly, one study demonstrated an increased prevalence of abnormally low thyroid hormone levels (hypothyroidism) in patients with gout. In patients at risk of developing gout, certain conditions can precipitate acute attacks of gout. These conditions includedehydration, injury to the joint, fever, excessive eating, heavy alcohol intake, and recent surgery. Gout attacks triggered by recent surgery are probably related to changes in the body-fluid balance as patients temporarily discontinue normal oral fluid intake in preparation for and after their operation. Pathophysiology Gout is a disorder of purine metabolism and occurs when its final metabolite, uric acid, crystallizes in the form of monosodium urate, precipitating in joints, on tendons, and in the surrounding tissues. These crystals then trigger a local immunemediated inflammatory reaction with one of the key proteins in the inflammatory cascade being interleukin 1. An evolutionary loss of uricase, which breaks down uric acid, in humans and higher primates is what has made this condition so common. The triggers for precipitation of uric acid are not well understood. While it may crystallize at normal levels, it is more likely to do so as levels increase. Other factors believed to be important in triggering an acute episode of arthritis include cool temperatures, rapid changes in uric acid levels, acidosis, articular hydration, and extracellular matrix proteins, such as proteoglycans, collagens, and chondroitin sulfate. The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected. Rapid changes in uric acid may occur due to a number of

factors, including trauma, surgery, chemotherapy, diuretics, and stopping or starting allopurinol. Calcium channel blockers and losartan are associated with a lower risk of gout as compared to other medications for hypertension Manifestations The small joint at the base of the big toe is the most common site of an acute gout attack of arthritis. An acute attack of gouty arthritis at the base of the big toe is medically referred to as podagra. Other joints that are commonly affected include the ankles, knees, wrists, fingers, and elbows. Acute gout attacks are characterized by a rapid onset of pain in the affected joint followed by warmth, swelling, reddish discoloration, and marked tenderness. Tenderness can be intense so that even a blanket touching the skin over the affected joint can be unbearable. Patients can develop fever with the acute gout attacks. These painful attacks usually subside in hours to days, with or without medication. In rare instances, an attack can last for weeks. Most patients with gout will experience repeated attacks of arthritis over the years. Uric acid crystals can deposit in tiny fluid-filled sacs (bursae) around the joints. These urate crystals can incite inflammation in the bursae, leading to pain and swelling around the joints (a condition calledbursitis). In rare instances, gout leads to a more chronic type of joint inflammation that mimics rheumatoid arthritis. In chronic (tophaceous) gout, nodular masses of uric acid crystals (tophi) deposit in different soft-tissue areas of the body. Even though they are most commonly found as hard nodules around the fingers, at the tips of the elbows, in the ears, and around the big toe, tophi nodules can appear anywhere in the body. They have been reported in unexpected areas such as in the vocal cords or (rarely) even around the spinal cord. When tophi appear in the tissues, the gout condition is felt to represent a substantial overload of uric acid within the body.

Diagnostic Procedures Gout is suspected when a patient reports a history of attacks of painful arthritis, particularly at the base of the toes. Ankles and knees are the next most commonly involved joints in gout. Gout usually attacks one joint at a time, while other arthritis conditions, such as systemic lupus and rheumatoid arthritis, usually attack multiple joints simultaneously. The most reliable test for gout is finding uric acid crystals in a sample of the joint fluid obtained by joint aspiration(arthrocentesis). Arthrocentesis is a common office procedure performed under local anesthesia. Using sterile technique, fluid is withdrawn (aspirated) from the inflamed joint using a syringe and needle. The joint fluid is then analyzed for uric acid crystals and for infection. Shiny, needle-like uric acid crystals are best viewed with a special polarizing microscope. The diagnosis of gout can also be made by finding these urate crystals from material aspirated from tophi nodules and

bursitis fluid. Although many doctors can do the procedure, rheumatologists are specialists who are particularly trained in this evaluation. Sometimes, patients with a classic history and symptoms of gout can be successfully treated and presumed to have gout without undergoing arthrocentesis. However, establishing a firm diagnosis is still preferable since other conditions can mimic gout. These include another crystal-induced arthritis called pseudogout, psoriatic arthritis, rheumatoid arthritis, and even infection in the joint. X-rays can sometimes be helpful and may show tophi-crystal deposits and bone damage as a result of repeated bouts of inflammation. X-rays can also be helpful for monitoring the effects of chronic gout on the joints.

Medical Management There are two key concepts essential to treating gout. First, it is critical to stop the acute inflammation of joints affected by gouty arthritis. Second, it is important to address the long-term management of the disease in order to prevent future gouty arthritis attacks and shrink gouty tophi crystal deposits in the tissues. T he treatment of an acute attack of gouty arthritis involves measures and medications that reduce inflammation. Preventing future acute gout attacks is equally as important as treating the acute arthritis. Prevention of acute gout involves maintaining adequate fluid intake, weight reduction, dietary changes, reduction in alcohol consumption, and medications to lower the uric acid level in the blood (reduce hyperuricemia). Maintaining adequate fluid intake helps prevent acute gout attacks. Adequate fluid intake also decreases the risk of kidney stone formation in patients with gout. Alcohol is known to have diuretic effects that can contribute to dehydration and precipitate acute gout attacks. Alcohol can also affect uric acid metabolism to cause hyperuricemia. Therefore, alcohol has two major effects that worsen gout by impeding (slowing down) the excretion of uric acid from the kidneys as well as by causing dehydration, both of which contribute to the precipitation of uric acid crystals in the joints. Gout diet Dietary changes can help reduce uric acid levels in the blood. Since purine chemicals are converted by the body into uric acid, purine-rich foods are avoided. Examples of foods rich in purines include shellfish and organ meats such as liver, brains, kidneys, and sweetbreads. Researchers have reported, in general, that meat or seafood consumption increases the risk of gout attacks, while dairy food consumption seemed to reduce the risk. Protein intake or purine-rich vegetable consumption was not associated with an increased risk of gout. Total alcohol intake was strongly associated with an increased risk of gout (beer and liquor were particularly strong factors). Fructose from the corn syrup in soft drinks also increases the risk of gout.

Weight reduction can be helpful in lowering the risk of recurrent attacks of gout. This is best accomplished by reducing dietary fat and calorie intake, combined with a regular aerobic exercise program. Pharmacological Management There are three aspects to the treatment of gout with medications. First, pain relievers such as acetaminophen (Tylenol) or other more potent analgesics are used to manage pain. Secondly, anti-inflammatory agents such as nonsteroidal antiinflammatory drugs (NSAIDS), colchicine, and corticosteroids are used to decrease joint inflammation. Finally, medications are considered for managing the chronic underlying metabolic derangement that causes hyperuricemia and gout. This means treating the elevated levels of uric acid in the blood with medications that reduce these levels. NSAIDS such as indomethacin (Indocin) and naproxen (Naprosyn) are effective anti-inflammatory medications for acute gout. These medications are tapered after the arthritis resolves. Common side effects of NSAIDS include irritation of the gastrointestinal system, ulceration of the stomach and intestines, and even intestinal bleeding. People who have a history ofallergy to aspirin or nasal polyps should avoid NSAIDS because of the risk of an intense allergic (anaphylactic) reaction. Colchicine (Colcrys) for acute gout is administered by mouth to reduce inflammation as well as to prevent gouty arthritis attacks while correcting hyperuricemia with medications such as allopurinol (Zyloprim) or febuxostat(Uloric). For acute attacks, it is given hourly or every two hours until there is significant improvement in pain or the patient develops gastrointestinal side effects such as severe diarrhea. For prevention, it is given once or twice daily. Other common side effects of colchicine include nausea and vomiting. Corticosteroids such as prednisone, given in short courses, are powerful antiinflammatory agents for treating acute gout. They can be administered orally or injected directly into the inflamed joint. Corticosteroids can be prescribed to patients who have accompanying kidney, liver, or gastrointestinal problems. Long-term chronic use of corticosteroids is discouraged because of serious long-term side effects. In addition to medications for acute gout attacks, other drugs can be taken over prolonged periods to lower blood uric acid levels. Lowering blood uric acid levels reduces the risk of recurrent attacks of arthritis, kidney stones, and kidney disease, and also slowly dissolves hard tophi deposits. Medicines used to lower blood uric acid level work either by increasing the kidney's excretion of uric acid or by decreasing the body's production of uric acid from the purines in foods. These medicines are generally not started until after the inflammation from acute gouty arthritis has subsided because they can worsen the attack. If they are already being taken prior to the attack, they are continued and only adjusted after the attack has resolved. Probenecid (Benemid) and sulfinpyrazone (Anturane) are medications that are commonly used to decrease uric acid blood levels by increasing the excretion of uric acid into the urine. Since these drugs can, in rare instances, cause kidney stones, they should be avoided by those patients with a history of kidney stones. These medications should be taken with plenty of fluid so as to promote the rapid passage of uric acid out of the urinary system in order to prevent kidney stone formation.

Allopurinol lowers the blood uric acid level by preventing uric acid production. It actually blocks the metabolic conversion from purines in foods to uric acid. This medication is used with caution in patients with poor kidney function, as they are at a particular risk of developing side effects, including severe rash and liver damage. Febuxostat was approved by the U.S. Food and Drug Administration (FDA) for the chronic management of hyperuricemia from gout in 2009. Febuxostat has been shown to be more effective than allopurinol in preventing acute attacks of gouty arthritis and is effective in shrinking tophi deposits of uric acid in the tissues such as the fingers, elbows, and ears. Because febuxostat is not significantly metabolized by the kidneys, it may have advantages over allopurinol in patients with underlying kidney disease. While taking febuxostat, patients have uric acid levels and liver function blood tests monitored regularly. Again, uric acid-lowering medications such as allopurinol and febuxostat are generally not started in patients who are having acute attacks of gout. These medications, when started during an acute attack, actually can worsen the acute inflammation. Therefore, uric acid-lowering drugs are usually instituted only after complete resolution of the acute arthritis attacks, but if patients are already taking these medications, they are maintained at the same doses during the acute attacks. In some patients, increasing the dose of uric-acid-lowering medications can precipitate gout attacks. In these patients, low doses of colchicine can be given to prevent the precipitation of acute gout. It is essential to monitor the blood level of uric acid regularly once uric-acidlowering medications are used for optimal maintenance, as the uric acid metabolism can change over time. Home remedies which can alleviate the symptoms of acute gout include resting and elevating the inflamed joint. Ice-pack applications can sometimes make the inflammation worse by causing more uric acid to form crystals in the involved area. Patients should avoid aspirin-containing medications, when possible, because aspirin prevents kidney excretion of uric acid.
RHEUMATOID ARTHRITIS

Rheumatoid arthritis is defined as a persistent inflammatory disease affecting peripheral joints symmetrically, altering the cartilage, eroding the bone and leading to ankylosis. Rheumatoid arthritis affects 1% of the general population, is more common in women than in men, the women / men ratio is 3 / 1, and most often is diagnosed between 35 and 50 years. Rheumatoid Arthritis Causes The exact cause of rheumatoid arthritis is unknown, but pathogenic, is accepted the existence of genetic predisposition, against which environmental antigens or endogenous antigens can cause immune mechanism which is responsible for the appearance of the inflammation in the peripheral joints.

1. Genetic predisposition. Rheumatoid arthritis is four times more common in first degree relatives of patients with seropositve rheumatoid arthritis and 10% of patients with rheumatoid arthritis have a first-degree relative with the same disease. Major genetic risk for rheumatoid arthritis is HLA DR4 in populations of northern Europe and HLA DRB 10402 in populations of southern Europe. 2. Possible antigens. There is evidence on the viral nature of antigens that can trigger a immune response in rheumatoid arthritis (Epstein Barr virus, retroviruses) or bacterial antigens (Mycoplasma arthritis, Mycobacterium tuberculosis, Proteus mirabilis). 3. Pathogenic immune process. It is supported both by the cellular argument, consisting in the presence in the synovium of a large number of lymphocytes T helper (CD4 +) and by the humoral argument: the production of local rheumatoid factor, the circulating immune complexes of IgM and IgG and the complement activation.

Rheumatoid Arthritis Symptoms In the onset period: The first sign is morning joint stiffness, with a progressive duration, relevant when is exceeding 60 minutes. Joint pain occur at short intervals, especially in active movements, and swollen joints (arthritis). Joint pain and arthritis are symmetrical and most commonly interested are metacarpophalangeal joints, proximal interphalangeal (especially the finger 2 and 3) and corresponding joints from the leg. Sometimes rheumatoid arthritis, can have a onset with the inflammation of radiocarpal or of carpal joints. In 10% 20% of cases, the onset is acute, passing sometimes in one night, from the period of apparent health, to the clinical picture of acute generalized rheumatoid arthritis.

In the period of clinical symptoms, there are articular events and extraarticular events. Articular manifestations. The most frequent are interested the small joints of hands, the wrists, knees and feet. In time the disease can affect the ribs, shoulders, sternoclavicular joints, hips and ankles. In general, it might be interested any joint in the body. Hands. Proximal interphalangeal joint swelling, give the fingers the appearance of spindle. It is one of the early and characteristic signs. Late, will appear the deformation of the fingers; Fists. Radio carpal joint is constantly affected in rheumatoid arthritis. Functional is found a reduction of mobility in wrist, both in terms of flexion, and extension; Knees. Inflammation with edema in the knee joint, is frequently a sign of rheumatoid arthritis; Feet and ankles. The most common are interested metatarsophalangeal joints, with valgus deformity of the toe, causing pain in walking. Extraarticular manifestations of rheumatoid arthritis. All extraarticular complications occur almost exclusively in patients with seropositve rheumatoid arthritis. Skin: subcutaneous nodule, with hard consistency and diameter about 1 cm. They occur in the joint structures, especially in areas of pressure: elbow, hand, foot, etc.; Muscle: swelling and eventually atrophy, especially in the interosseous muscles of hand and of foot; Cardiac manifestations represented by pericarditis (more frequent) and rhythm disturbances, valvular stenosis or regurgitation; Respiratory manifestations: pleuritis, pulmonary fibrosis; Ophthalmologic manifestations are rare. A particular form of rheumatoid arthritis is Sjogrens syndrome: rheumatoid arthritis, with dry corneas, dry mouth, which may be associated with hypertrophy of the parotid glands.

Felty syndrome is defined by the triad: rheumatoid arthritis, splenomegaly and neutropaenia. Paraclinical examination: 1. Rheumatoid factor positive in 80% of cases, is useful for diagnosis in a titer which is higher then 1 / 80. Rheumatoid factor is dividing rheumatoid arthritis into two classes: seropositive rheumatoid arthritis (with rheumatoid factor) and seronegative rheumatoid arthritis (without rheumatoid factor). Positivity rheumatoid factor occurs at a variable interval of time from onset of clinical disease. Usually when there are extraarticular manifestations, rheumatoid factor is present in high titers. Rheumatoid factor is present in 6% 8% of the general population and can occur with other autoimmune diseases, which may reduce its specificity. 2. Antinuclear antibodies, occurring in 30% 40% of cases. 3. Nonspecific inflammation tests: ESR accelerated, fibrinogen and C-reactive protein are increased. 4. Synovial fluid examination, shows the presence of leukocytes between 5.000/mm and 20.000/mm, low or normal glucose, low complement and the presence of polymorphonuclear. 5. Anemia characteristic for chronic inflammation. 6. Radiological changes in rheumatoid arthritis is evolving in stages, as follows:

Stage I (early): the presence or not of osteoporosis, but without bone erosion; Stage II (moderate): the presence of osteoporosis, with or without bone destruction, with or without mild cartilage damage, but without the presence of joint deformities; Stage III (severe): the presence of osteoporosis accompanied by bone destruction and cartilage damage, joint deformation accompanied by dislocations, but no bone ankylosis; Stage IV (terminal): the presence of stage III criteria, plus fibrosis and joint stiffness .

7. Other osteoarticular imagistic examinations include bone scan and MRI, which can reveal early inflammatory changes that can not be highlighted on a standard radiography. Rheumatoid Arthritis Diagnosis Because the diagnosis of rheumatoid arthritis is not always easy, American College of Rheumatology proposed a series of diagnostic criteria: 1. Morning stiffness lasting at least one hour, at least 6 weeks; 2. Arthritis of three or more joints of the hand or foot, involving the simultaneous three joints, manifested by swelling, lasting at least 6 weeks; 3. Hand arthritis, at least one area of the hand joints with arthritis (metacarpophalngeal , wrist, interphalangeal joint), lasting at least 6 weeks; 4. Symmetrical arthritis, involving the same joints simultaneously; 5. Rheumatoid nodules; 6. Rheumatoid factor present; 7. Radiological changes typical for rheumatoid arthritis, which should include bone erosion or decalcification of the bone.

The diagnosis of rheumatoid arthritis requires the presence of at least four of the seven criteria listed.

To give a full diagnosis of rheumatoid arthritis should be taken into account the functional classification of the disease:

Class I: Any activity is possible; Class II: normal activities are possible, despite the pain and discomfort represented by limiting the mobility of one or more joints; Class III: low functional capacity, are possible only a few of the normal activities (is possible Self-care); Class IV: immobilization in bed or wheelchair, usually self-care measures are impossible.