ARTHRITIS

Introduction

Arthritis is a form of joint disorder that involves inflammation of one or more joints. There are over 100 different forms of arthritis. The major complaint by individuals who have arthritis is joint pain. Pain is often a constant and may be localized to the joint affected, such as the joints of the hips, knees, and spine. It can also affect the fingers, thumb, neck, and large toe. The pain from arthritis occurs due to inflammation that occurs around the joint, damage to the joint from disease, daily wear and tear of joint, muscle strains caused by forceful movements against stiff, painful joints and fatigue.

The most common form, osteoarthritis (degenerative joint disease) is a result of trauma to the joint, infection of the joint, or age. Other arthritis forms are rheumatoid arthritis, and gouty arthritis.

Anatomy and Physiology – The Skeletal System

Functions of the Skeleton

1. Support 2. Protection3. Helps make movements possible 4. Storage of Calcium5. Storage of Fat (Chemical Energy)

Bones

Types of Bones1. Long bones2. Short bones3. Flat bones4. Irregular bones5. Sesamoid bones

The Structure of Long Bone1. Diaphysis or shaft2. Medullary Cavity3. Epiphysis4. Articular Cartilage5. Endosteum6. Periosteum

Microscopic Structure of Bone and Cartilage

1. Bone Typesa. Spongy b. Compact

2. Cartilagea. Chondrocyte b. Matrix is gel-like

Bone Formation and Growth

A. The skeleton arises from fibrous membranes and hyaline cartilage during the first month of embryonic development.

B. The second ossification process, called endochondral ossification, occurs when hyaline cartilage is replaced by bone tissue.

C. Osteoblast form new bone, and osteoclasts resorb bone

Division of Skeleton

1. Axial skeleton 2. Appendicular skeleton

Joint (Articulations)

Kinds of Joints

1. Synarthroses2. Amphiarthroses3. Diarthoses

a. Structure of freely movable joints b. Articular cartilagec. Synovial membraned. Joint cavity

Types of Freely Movable Joints1. Ball and socket2. Hinge3. Pivot4. Saddle5. Gliding6. Condyloid

Pathophysiology

Osteoarthritis

Osteoarthritis is called degenerative joint disease or degenerative arthritis. Osteoarthritis -- also called OA -- usually does not affect other joints unless previous injury or excessive stress is involved. It affects about 33 million Americans and is the most common chronic joint condition.

Osteoarthritis results from overuse of joints. It can be the consequence of demanding sports, obesity, or aging. If you were an athlete or dancer in high school or college, you may be wondering why your knee or hip aches when you climb out of bed in the morning. Ask your doctor about osteoarthritis. It often strikes early in life with athletes or those who suffered an injury in young adulthood. Osteoarthritis in the hands is frequently inherited and often happens in middle-aged women.

Osteoarthritis is most common in joints that bear weight -- such as the knees, hips, feet, and spine. It often comes on gradually over months or even years. Except for the pain in the affected joint, you usually do not feel sick, and there is no unusual fatigue or tiredness as there is with some other types of arthritis.

With osteoarthritis, the cartilage gradually breaks down. Cartilage is a slippery material that covers the ends of bones and serves as the body's shock absorber. As more damage occurs, the cartilage starts to wear away, or it doesn't work as well as it once did to cushion the joint. As an example, the extra stress on knees from being overweight can cause damage to knee cartilage. That, in turn, causes the cartilage to wear out faster than normal.

As the cartilage becomes worn, cushioning effect of the joint is lost. The result is pain when the joint is moved. Along with the pain, sometimes you may hear a grating sound when the roughened cartilage on the surface of the bones rubs together. Painful spurs or bumps may appear on the end of the bones, especially on the fingers and feet. While not a major symptom of osteoarthritis, inflammation may occur in the joint lining as a response to the breakdown of cartilage.

Rheumatoid Arthritis

Rheumatoid arthritis is a form of autoimmunity, the causes of which are still incompletely known. It is a systemic (whole body) disorder principally affecting synovial tissues.

The key pieces of evidence relating to pathogenesis are:

A genetic link with HLA-DR4 and related allotypes of MHC Class II and the T cell-associated protein PTPN22.

A link with cigarette smoking that appears to be causal. A remarkable deceleration of disease progression in many cases by blockade of the cytokine TNF

(alpha). A similar dramatic response in many cases to depletion of B lymphocytes, but no comparable

response to depletion of T lymphocytes. A more or less random pattern of whether and when predisposed individuals are affected. The presence of autoantibodies to IgGFc, known as rheumatoid factors (RF), and antibodies to

citrullinated peptides (ACPA).

Gouty Arthritis

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 immune-mediated inflammatory reaction with one of the key proteins in the inflammatory cascade being interleukin 1β. 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.

Risk Factors

Osteoarthritis Age Gender Obesity Work and Leisure

Factors Exercise Physical Deformities

Rheumatoid Arthritis Age Gender Family history Smoking

Gouty Arthritis Lifestyle factors Medical conditions Certain medications Family history of gout Age Gender

Diagnosis / Signs and Symptoms

Symptoms of osteoarthritis may include:

deep, aching pain in a joint difficulty dressing or combing hair difficulty gripping objects difficulty sitting or bending over fatigue joint may be warm to touch morning stiffness for less than an hour pain when walking stiffness after resting swelling of joint

Diagnosis and tests

Osteoarthritis is often visible in x-rays. Cartilage loss is suggested by certain characteristics of the images:

• The normal space between the bones in a joint is narrowed.

• There is an abnormal increase in bone density.

• Bony projections, cysts, or erosions are visible.

If the doctor suspects other conditions, or if the diagnosis is uncertain, additional tests are necessary.

It is important to note that a negative x-ray does not rule out osteoarthritis. Likewise, some people may have minimal symptoms even though an x-ray clearly shows they have arthritis.

An MRI exam of an arthritic joint is generally not needed, unless the doctor suspects other causes of pain.

Symptoms of rheumatoid arthritis

RA usually affects joints on both sides of the body equally. Wrists, fingers, knees, feet, and ankles are the most commonly affected.

The disease often begins slowly, usually with only minor joint pain, stiffness, and fatigue.

Joint symptoms may include:

Morning stiffness, which lasts more than 1 hour, is common. Joints may feel warm, tender, and stiff when not used for an hour.

Joint pain is often felt on the same joint on both sides of the body. Over time, joints may lose their range of motion and may become deformed.

Other symptoms include:

Chest pain when taking a breath (pleurisy) Dry eyes and mouth (Sjogren syndrome) Eye burning, itching, and discharge Nodules under the skin (usually a sign of more severe disease) Numbness, tingling, or burning in the hands and feet

Diagnosis and tests

There is not test that can determine for sure whether you have RA. Most patients with RA will have some abnormal test results, although for some patients, all tests will be normal.

Two lab tests that often help in the diagnosis are:

• Rheumatoid factor test• Anti-CCP antibody test

Other tests that may be done include:

• Complete blood count• C-reactive protein• Erythrocyte sedimentation rate• Joint ultrasound or MRI• Joint x-rays• Synovial fluid analysis

Symptoms of gouty arthritis

Gout can present in a number of ways, although the most usual is a recurrent attack of acute inflammatory arthritis (a red, tender, hot, swollen joint). The metatarsal-phalangeal joint at the base of the big toe is affected most often, accounting for half of cases. Other joints, such as the heels, knees, wrists and fingers, may also be affected. Joint pain usually begins over 2–4 hours and during the night. The reason for onset at night is due to the lower body temperature then. Other symptoms that may occur along with the joint pain include fatigue and a high fever.

Long-standing elevated uric acid levels (hyperuricemia) may result in other symptomatology, including hard, painless deposits of uric acid crystals known as tophi. Extensive tophi may lead to chronic arthritis due to bone erosion. Elevated levels of uric acid may also lead to crystals precipitating in the kidneys, resulting in stone formation and subsequent urate nephropathy.

Diagnosis and tests

Gout on X-rays of a left foot. Typical location at the big toe joint. Note also the soft tissue swelling at the lateral border of the foot.

Spiked rods of uric acid (MSU) crystals from a synovial fluid sample photographed under a microscope with polarized light. Formation of uric acid crystals in the joints is associated with gout.

Gout may be diagnosed and treated without further investigations in someone with hyperuricemia and the classic podagra. Synovial fluid analysis should be done, however, if the diagnosis is in doubt. X-rays, while useful for identifying chronic gout, have little utility in acute attacks.

Synovial fluid. A definitive diagnosis of gout is based upon the identification of monosodium urate (MSU) crystals in synovial fluid or a tophus. All synovial fluid samples obtained from undiagnosed inflamed joints should be examined for these crystals. Under polarized light microscopy, they have a needle-like morphology and strong negative birefringence. This test is difficult to perform, and often requires a trained observer. The fluid must also be examined relatively quickly after aspiration, as temperature and pH affect their solubility.

Blood tests

Hyperuricemia is a classic feature of gout; gout occurs, however, nearly half of the time without hyperuricemia, and most people with raised uric acid levels never develop gout. Thus, the diagnostic utility of measuring uric acid level is limited. Hyperuricemia is defined as a plasma urate level greater than 420 μmol/L (7.0 mg/dL) in males and 360 μmol/L (6.0 mg/dL) in females. Other blood tests commonly performed are white blood cell count, electrolytes, renal function, and erythrocyte sedimentation rate (ESR). However, both the white blood cells and ESR may be elevated due to gout in the absence of infection. A white blood cell count as high as 4.0×109/L (40,000/mm3) has been documented.

Differential diagnosis. The most important differential diagnosis in gout is septic arthritis. This should be considered in those with signs of infection or those who do not improve with treatment. To help with diagnosis, a synovial fluid Gram stain and culture may be performed. Other conditions which present similarly include pseudogout and rheumatoid arthritis. Gouty tophi, in particular when not located in a joint, can be mistaken for basal cell carcinoma, or other neoplasms.

Complications

Possible Complications of Osteoartritis arthritis:

Adverse reactions to drugs used for treatment Decreased ability to perform everyday activities, such as personal hygiene, household chores, or

cooking Decreased ability to walk Surgical complications

Possible Complications of Rheumatoid arthritis:

Damage to the lung tissue (rheumatoid lung) Increased risk of hardening of the arteries Spinal injury when the neck bones become damaged Inflammation of the blood vessels (rheumatoid vasculitis), which can lead to skin, nerve, heart,

and brain problems

Swelling and inflammation of the outer lining of the heart (pericarditis) and of the heart muscle (myocarditis), which can lead to congestive heart failure

Possible Complications of Gouty arthritis:

Chronic gouty arthritis Kidney stones Deposits in the kidneys, leading to chronic kidney failure

Treatment

Osteoarthritis

There is currently no cure for osteoarthritis, but treatments are improving. Available treatments include:

Nonsteroidal anti-inflammatory drugs (NSAIDs). These both relieve pain and reduce inflammation. NSAIDs range from aspirin, ibuprofen (found in Advil and Motrin), ketoprofen (Actron and Orudis) and naproxen sodium (Aleve) to more powerful prescription drugs. Possible side effects of NSAIDs include ringing in the ears, ulcers, stomach or intestinal bleeding, kidney damage, heart failure, fluid retention and cognitive changes.

Topical pain relievers. Over-the-counter creams, gels, ointments and sprays can temporarily relieve arthritis pain and reduce inflammation in joints close to the surface of the skin, such as fingers, knees and elbows. Topical pain relievers include trolamine salicylate (found in Aspercreme and Sportscreme); methyl salicylate, menthol and camphor (found in Double Ice ArthriCare, Eucalyptamint, Icy Hot and Ben-Gay); or capsaicin from the seeds of hot chili peppers (found in Zostrix and Capzasin-P).

COX-2 inhibitors. These are as effective for managing pain and inflammation as NSAIDs, but they have fewer stomach-injuring side effects. Examples include celecoxib (Celebrex) and rofecoxib (Vioxx). They are more expensive than NSAIDs and do have side effects of their own, including fluid retention (which may worsen heart failure). They may also be associated with an increased risk of heart attack, transient ischemic attack or stroke.

Antidepressants. One in five people with a chronic disease and pain also has depression. Antidepressants can alleviate depression and help reduce chronic pain. The most common ones used for arthritis treatment are amitriptyline (Elavil, Endep), desipramine (Norpramin, Pertofrane), imipramine (Tofranil, Norfranil) and nortriptyline (Pamelor, Aventyl).

Corticosteroids. Injected into the joint, corticosteroids can relieve some pain for four to six months. Knee joints may be treated with Hylan G-F20 (Synvisc) and hyaluronate (Hyalgan) but requires three to five weekly injections. Pain relief is usually achieved more slowly with shots than with corticosteroids, but it lasts longer.

Joint replacement. In recent years, joint replacement surgery has become the most important surgical treatment for arthritis. Although hip joints are the most commonly replaced joints, replacements can be done for knee, shoulder, elbow, finger or ankle joints.

Other surgical procedures. Surgery may be performed to remove loose pieces of bone or cartilage that may cause pain or locked joints. These procedures usually use the assistance of an arthroscope (a small tube inserted into the joint through which the surgeon works). Surgery can

also be used to reposition the bones, help correct deformities or fuse bones to increase stability and reduce pain. The fused joint, however, has no flexibility.

To effectively manage the condition, those with osteoarthritis can also:

Exercise regularly. Exercise can strengthen muscles, increase range of motion, improve balance and help reduce stress. Good exercises include walking, stationary bicycle riding, water exercises or Tai chi. Be sure to stand up straight while exercising. Avoid exercise if your joint is tender, injured or severely inflamed. If you feel a pain you haven't had before, stop exercising. New pain that lasts m

ore than two hours after exercise usually means you've overdone it. Control weight. Excess body weight adds stress on joints in back, hips, knees and feet - where

arthritis pain is commonly felt. Excess weight also can make joint surgery more difficult and risky.

Eat a healthy diet. Eating a diet high in vegetables, whole grains and fruits helps maintain a proper weight and good health. There is, however, no special diet for treating arthritis, and eating any particular foods has not been proven to make joint pain or inflammation better or worse.

Know your limits. Rest when tired. Arthritis can make people prone to fatigue and muscle weakness. A rest or short nap that does not interfere with nighttime sleep may help.

Avoid actions that strain finger joints. For example, instead of a clutch-style purse, select one with a shoulder strap. Use hot water to loosen a jar lid and pressure from your palm to open it, or use a jar opener. Don't twist or use your joints forcefully.

Spread the weight of an object over several joints. Use both hands, for example, to lift a heavy pan. Try using a walking stick or cane.

Take breaks to relax, and stretch regularly. Maintain good posture. The easiest way to improve your posture is by walking. The faster you

walk, the harder your muscles must work to keep you upright. Some people find that swimming also helps improve their posture.

Use your strongest muscles and favor large joints. Don't push open a heavy glass door. Lean into it. To pick up an object, bend your knees and squat while keeping your back straight.

Apply heat. Heat may ease your pain, relax painful muscles and increase blood flow. You may find it helpful before exercising. An easy way to apply heat is to take a 15-minute hot shower or bath. Other options are a hot pack, an electric heating pad on its lowest setting or a radiant heat lamp with a 250-watt reflector heat bulb. If your skin has poor sensation or if you have poor circulation, don't use heat treatment.

Apply cold for occasional flare-ups. Cold may dull the sensation of pain in the first day or two. Cold also decreases muscle spasms. Don't use cold treatments if you have poor circulation or numbness.

Wear comfortable, cushioned shoes that support your weight. Practice relaxation. Hypnosis, guided imagery, deep breathing and muscle relaxation can all help

control pain. Keep a positive attitude. Studies show that people who take control of their treatment and

actively manage their arthritis have less pain and function better. Make a plan with your doctor for managing your arthritis. This may help you feel that you're in charge of your disease, rather than vice versa.

Use braces, a cane or special tools and gadgets that help you have an active, independent life without joint strain.

Take medications as recommended. Taking them regularly instead of waiting for pain to build will lessen the overall intensity of discomfort.

Rheumatoid Arthritis

RA usually requires lifelong treatment, including medications, physical therapy, exercise, education, and possibly surgery. Early, aggressive treatment for RA can delay joint destruction.

MEDICATIONS

Disease modifying antirheumatic drugs (DMARDs): These drugs are the first drugs usually tried in patients with RA. They are prescribed in addition to rest, strengthening exercises, and anti-inflammatory drugs.

Methotrexate (Rheumatrex) is the most commonly used DMARD for rheumatoid arthritis. Leflunomide (Arava) andsulfasalazine may also be used.

These drugs may have serious side effects, so you will need frequent blood tests when taking them.

Anti-inflammatory medications: These include aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naprosen.

Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems.

Celecoxib (Celebrex) is another anti-inflammatory drug, but it is labeled with strong warnings about heart disease and stroke. Talk to your doctor about whether COX-2 inhibitors are right for you.

Antimalarial medications: This group of medicines includes hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine), and is usually used along with methotrexate. It may be weeks or months before you see any benefit from these medications.

Corticosteroids: These medications work very well to reduce joint swelling and inflammation. Because of long-term side effects, corticosteroids should be taken only for a short time and in low doses when possible.

BIOLOGIC AGENTS:

Biologic drugs are designed to affect parts of the immune system that play a role in the disease process of rheumatoid arthritis.

They may be given when other medicines for rheumatoid arthritis have not worked. At times, your doctor will start biologic drugs sooner, along with other rheumatoid arthritis drugs.

Most of them are given either under the skin (subcutaneously) or into a vein (intravenously). There are different types of biologic agents:

White blood cell modulators include: abatacept (Orencia) and rituximab (Rituxan) Tumor necrosis factor (TNF) inhibitors include: adalimumab (Humira), etanercept (Enbrel),

infliximab (Remicade), golimumab (Simponi), and certolizumab (Cimzia) Interleukin-6 (IL-6) inhibitors: tocilizumab (Actemra)

Biologic agents can be very helpful in treating rheumatoid arthritis. However, people taking these drugs must be watched very closely because of serious risk factors:

Infections from bacteria, viruses, and fungi Leukemia or lymphoma Psoriasis

SURGERY

Occasionally, surgery is needed to correct severely damaged joints. Surgery may include:

Removal of the joint lining (synovectomy) Total joint replacement in extreme cases; may include total knee, hip replacement, ankle

replacement, shoulder replacement, and others

PHYSICAL THERAPY

Range-of-motion exercises and exercise programs prescribed by a physical therapist can delay the loss of joint function and help keep muscles strong.

Sometimes therapists will use special machines to apply deep heat or electrical stimulation to reduce pain and improve joint movement.

Joint protection techniques, heat and cold treatments, and splints or orthotic devices to support and align joints may be very helpful.

Frequent rest periods between activities, as well as 8 to 10 hours of sleep per night, are recommended.

GA

The initial aim of treatment is to settle the symptoms of an acute attack. Repeated attacks can be prevented by different drugs used to reduce the serum uric acid levels. Ice applied for 20 to 30 minutes several times a day decreases pain. Options for acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and steroids, while options for prevention include allopurinol, febuxostat and probenecid. Lowering uric acid levels can cure the disease. Treatment of comorbidities is also important.

NSAIDs

NSAIDs are the usual first-line treatment for gout, and no specific agent is significantly more or less effective than any other. Improvement may be seen within 4 hours, and treatment is recommended for 1–2 weeks. They are not recommended, however in those with certain other health problems, such as gastrointestinal bleeding, renal failure, or heart failure. While indomethacin has historically been the most commonly used NSAID, an alternative, such as ibuprofen, may be preferred due to its better side effect profile in the absence of superior effectiveness. For those at risk of gastric side effects from NSAIDs, an additional proton pump inhibitor may be given.

Colchicine

Colchicine is an alternative for those unable to tolerate NSAIDs. Its side effects (primarily gastrointestinal upset) limit its usage. Gastrointestinal upset, however, depends on the dose, and the risk can be decreased by using smaller yet still effective doses. Colchicine may interact with other commonly prescribed drugs, such as atorvastatin and erythromycin, among others.

Steroids

Glucocorticoids have been found to be as effective as NSAIDs[37] and may be used if contraindications exist for NSAIDs.[2] They also lead to improvement when injected into the joint; the risk of a joint infection must be excluded, however, as they worsen this condition.[2]

Pegloticase

Pegloticase (Krystexxa) was approved in the USA to treat gout in 2010. It will be an option for the 3% of people who are not adequately treated with other medications due to their association with severe allergic reactions. Pegloticase is administered as an intravenous infusion every two weeks. As of March 2010, however, no double blind, placebo controlled trials have been completed.

Prophylaxis

A number of medications are useful for preventing further episodes of gout, including xanthine oxidase inhibitor (including allopurinol and febuxostat) and uricosurics (including probenecid and sulfinpyrazone). They are not usually commenced until one to two weeks after an acute attack has resolved, due to theoretical concerns of worsening the attack, and are often used in combination with either an NSAID or colchicine for the first 3–6 months. They are not recommended until a person has suffered two attacks of gout, unless destructive joint changes, tophi, or urate nephropathy exist, as it is not until this point that medications have been found to be cost effective. Urate-lowering measures should be increased until serum uric acid levels are below 300–360 µmol/L (5.0-6.0 mg/dL) and are continued indefinitely. If these medications are being used chronically at the time of an attack, it is recommended they be continued.

As a rule of thumb, uricosuric drugs are preferred if there is undersecretion of uric acid, in turn indicated if a 24-hour collection of urine results in a uric acid amount of less than 800mg. They are, however, contraindicated if the person has a history of renal stones. In contrast, a 24-hour urine excretion of more than 800mg indicates overproduction, and xanthine oxidase inhibitors are preferred. Overall, probenecid appears to be less effective than allopurinol.

Xanthine oxidase inhibitors (including allopurinol and febuxostat) block uric acid production, and long term therapy is safe and well tolerated, and can be used in people with renal impairment or urate stones, although allopurinol has caused hypersensitivity in a small number of individuals. In such cases, the alternative drug febuxostat has been recommended.