ARTHRITIS IS THE NAME GIVEN FOR PAINFUL JOINT DISEASES

About Author:
Kapil Sharma
Yaresun Pharmaceutical Pvt. Ltd., India.
pharma_kapil@rediffmail.com

Introduction:
Arthritis is the name given for painful joint diseases. Arthritis one of the most common health problems in india. Arthritis also is the leading cause of disability. Rheumatoid arthritis (RA) is a chronicinflammatory condition of the connective tissues throughout the body, but especially around the joints. The main sign of RA is often stiff, painful, and swollen joints.  Areas of typical complaint include the hands, feet, wrists, ankles, and knees.  Depending on the severity of the condition, these areas may eventually become deformed. The exact cause of rheumatoid arthritis remains, largely, unknown.  It has been theorized that a number of genetic and environmental factors may contribute to the disease process, and may include genetics, poor nutrition, lifestyle, chronic stress in rheumatoid arthritis, the joint lining, or synovial membrane, becomes inflamed and the joints become stiff and swollen. The synovial membrane secretes a slippery fluid that covers the cartilage-covered joints and reduces the friction between adjacent joints.The chronic inflammation of rheumatoid arthritis eventually leads to destruction of the cartilage covering the ends of the joints and underlying bone.  In many cases this damage causes joint deformity.

Rheumatoid arthritis is an autoimmune disease, in which the immune system produces antibodies (called rheumatoid factor) that attack the body's own tissues. Because of this, Rheumatoid arthritis is also considered a connective tissue disorder.  Collagen-rich connective tissues such as the eyes, lungs, heart, and blood vessels, may be adversely affected by RA and its accompanying inflammation.  Living with rheumatoid arthritis can mean living with chronic pain, fatigue and joint stiffness. Thousands of people have benefited from developing and following plans to help them manage their symptoms health professional can develop a medical treatment plan that may include medication and other therapies. Early medical treatment can help us avoid disabling joint changes and chronic pain. Besides following our medical treatment plan, there are several steps, which can take to maintain our normal life and activities. This is often called self-management. The first steps include: learning as much as we can about rheumatoid arthritis,Learning ways to reduce joint pain, fatigue, and stiffness,Taking an active role in managing your rheumatoid arthritis.¹

Reference Id: PHARMATUTOR-ART-1407

1.2 Definition:
Rheumatoid arthritis, known as Still's disease when it affects children, is a condition that causes inflammation of joints and associated pain, swelling, and stiffness. Rheumatoid arthritis causes the body's own immune system to attack joint tissue, breaking down collagen, cartilage, and sometimes bone or other organs. This chronic disease varies between people and fluctuates over time, often marked by symptoms that improve only to re-emerge later. In some cases rheumatoid arthritis is mild and lasts only a few months (this kind of rheumatoid arthritis is called type 1), while in others the disease becomes progressively complicated by disability and other health problems, lasting many years 
 Rheumatoid arthritis most often affects the wrist and finger joints closest to the hand, but can also affect joints in the feet and throughout the body. Anyone can be affected by rheumatoid arthritis, but women are more likely to develop symptoms, which most often begin between the ages of 20 and 30. The causes of rheumatoid arthritis are not yet understood, but many effective strategies have been developed to manage its symptoms.¹

1.3 Rheumatoid Arthritis Sign. And Symptoms:
Rheumatoid arthritis usually develops slowly over the course of several weeks to several months. This type of arthritis may chronically recur in week or month long episodes. In some cases, after many years, the attacks gradually stop and the disease may burn out itself though permanent disability may result.

 General symptoms include:

• Fatigue from Rheumatoid symptoms
• Pale skin
• Shortness of breath on exertion
• Low-grade fever
• Loss of appetite

Specific symptoms may include:

• Painful, stiff, tender and swollen joints, most often of the hands, but may also involve other joints of the feet, wrists, elbows, shoulders, hips, knees, and ankles.
• Joint pain and stiffness is typically worse in the morning and improves as the day goes on.

Chronic disease can lead to disability and deformities, most typically affecting the middle joint of the fingers so that they become spindle-shaped.^1,2

1.4 Variability Of Symptoms Among People With The Disease:

Symptoms in other parts of the body besides the joints-
Some people also experience the effects of rheumatoid arthritis in places other than the joints. About one-quarter develop rheumatoid nodules. These are bumps under the skin that often form close to the joints. Many people with rheumatoid arthritis develop anemia, or a decrease in the normal number of red blood cells. Other effects, which occur less often, include neck pain and dry eyes and mouth. Very rarely, people may have inflammation of the blood vessels, the lining of the lungs, or the sac enclosing the heart.    In people with rheumatoid arthritis, the immune system predominantly targets the lining (synovium) that covers various joints. Inflammation of the synovium is usually symmetrical (occurring equally on both sides of the body) and causes pain, swelling andstiffness of the joints. These features distinguish rheumatoid arthritis from osteoarthritis, which is a more common and degenerative "wear-and-tear" arthritis.In rheumatoid arthritis, the hands are most commonly affected, but it can affect most joints of the body. Inflammation begins in the synovial lining and can spread to the entire joint. Painful and knobby bone growths in the fingers are common, but usually not crippling to osteoarthritis. The disease is often mild, but can be quite severe. Rheumatoid arthritis (RA) can be one of the more disabling forms of arthritis. Signs of RA often include morning stiffness, swelling in three or more joints, swelling of the same joints on both sides of the body (both hands, for example), and bumps (or nodules) under the skin most commonly found near the elbow. RA can occur at any age and affects women about three times more often than men.²

1.5 Why Rheumatoid Arthritis Is Painful:
How joint pain and the destruction of cartilage are related is not fully understood. Cartilage itself does not cause pain because there are no nerve structures in cartilage to transmit pain signals. Most likely, the pain of rheumatoid arthritis is caused by the irritation of other tissues in and around the affected joints. Chemical-messenger substances, such as prostaglandin E2, that are associated with the disease process, may cause this irritation. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce pain because they inhibit the production of prostaglandin.²

1.6 Other Conditions That Can Cause Pain:
Pain and stiffness similar to rheumatoid arthritis symptoms can be caused by many other conditions. Even if injury or infection can be ruled out, anything from bunions to fibromyalgia or chronic fatigue syndrome can cause pain.
Only a medical professional can identify many sources of joint pain, because similar symptoms can result from other autoimmune diseases, from serious conditions such as cancer, or from many other kinds of arthritis.²

1.7 Mortality Rate Of Rheumatoid Arthritis:
Rheumatoid arthritis alone does not appear to decrease lifespan or make our real age older. However, complications that may develop in severe cases of rheumatoid arthritis contribute to a higher average mortality for people with this condition.

1.8 Pathology And Pathogenesis:
The swelling is due to an infiltration of cells of the immune system, such as macrophages, T lymphocytes and plasma cells. Some of these cells are self-reactive with target cell proteins, such as cartilage proteoglycan and heat shock proteins. As the disease progresses the immune cells release inflammatory cytokines (IL1, IL6 and TNFa) which damage the cartilage of the joints. Eventually granulation tissue forms over and under the cartilage (this is called a pannus) causing its erosion and eventual destruction.

1.10 Stages Of Rheumatoid Arthritis:³
1. First stage, synovitis (inflammation of the synovial membrane) develops from congestion and edema of the synovial membrane (membrane lining the capsule of a joint) and the joint capsule.
2. Formation of pannus (thickened layers of granulation tissue) marks the onset of the second stage. Pannus covers and invades cartilage and eventually destroys the joint capsule and bone.
3. Progression to the third stage is characterized by fibrous ankylosis - fibrous invasion of the pannus and scar formation that occludes the joint space. Bone atrophy and misalignment cause visible deformities and disrupt the articulation of opposing bones, causing muscle atrophy and imbalance and possibly partial dislocations or subluxations.
4. In the fourth stage, fibrous tissue calcifies, resulting in bony ankylosis and total immobility.

Patients with mild disease have fewer than six joints involved, no bone erosion on x-rays and no RA activity outside of the joints. Patients with moderate disease have 6-20 involved joints and may have joint space narrowing or erosions on x-rays.

 

2.1 Conditions that Can Cause Rheumatoid Arthritis:
Rheumatoid arthritis can occur independently from other conditions, but its causes and relationship to other diseases are not well understood. A different form of chronic arthritis can sometimes develop into rheumatoid arthritis. It is also possible that infections or other environmental triggers exist that can cause rheumatoid arthritis in people that already have a gene for the disease.

2.2 Cause Details For Rheumatoid Arthritis:³
A normal joint  is surrounded by a joint capsule that protects and supports it. Cartilage covers and cushions the ends of the two bones. The joint capsule is lined with a type of tissue called synovium, which produces synovial fluid. This clear fluid lubricates and nourishes the cartilage and bones inside the joint capsule.

In rheumatoid arthritis, the immune system, for unknown reasons, attacks a person's own cells inside the joint capsule. White blood cells that are part of the normal immune system travel to the synovium and cause a reaction. This reaction is called synovitis and results in the warmth, redness, swelling and pain that are typical symptoms of rheumatoid arthritis. During the inflammation process, the cells of the synovium grow and divide abnormally, making the normally thin synovium thick and resulting in a joint that is swollen and puffy to the touch.

As rheumatoid arthritis progresses, these abnormal synovial cells begin to invade and destroy the cartilage and bone within the joint. The surrounding muscles, ligaments and tendons that support and stabilize the joint become weak and unable to work normally. All of these effects lead to the pain and deformities often seen in rheumatoid arthritis. Doctors studying rheumatoid arthritis now believe that damage to bones begins during the first year or two that a person has the disease. This is one reason early diagnosis and treatments are so important in the management of rheumatoid arthritis. In rheumatoid arthritis, the synovium becomes inflamed, causing warmth, redness, swelling, and pain. As the disease progresses, abnormal synovial cells invade and erode, or destroy, cartilage and bone within the joint. Surrounding muscles, ligaments and tendons become weakened. Rheumatoid arthritis can also cause more generalized bone loss that may lead to osteoporosis (fragile bones that are prone to fracture). Rheumatoid arthritis is one of several "autoimmune" diseases so-called because a person's immune system attacks his or her own body tissues. we still do not know exactly what causes this to happen, but research over the last few years has begun to unravel the factors involved.

2.2.1 Genetic Factor:
We have found that certain genes that play a role in the immune system are associated with a tendency to develop rheumatoid arthritis. At the same time, some people with rheumatoid arthritis do not have these particular genes and other people have these genes but never develop the disease. This suggests that a person's genetic makeup is an important part of the story but not the whole answer. It is clear that more than one gene is involved in determining whether a person develops rheumatoid arthritis.

2.2.2 Environmental Factors:
Something must occur to trigger the disease process in people whose genetic makeup makes them susceptible to rheumatoid arthritis. An infectious agent such as a virus or bacterium appears likely, but the exact agent is not yet known. However rheumatoid arthritis is not contagious: A person cannot "catch" it from someone else.

2.2.3 Other Factors :
We think that a variety of hormonal factors may be involved. These hormones may promote the development of rheumatoid arthritis in a genetically susceptible person who has been exposed to a triggering agent from the environment. Even though all the answers aren't known, one thing is certain: Rheumatoid arthritis develops as a result of an interaction of many factors. We don’t know what causes RA but think it has something to do with a breakdown in the immune system, the body’s defense against disease. It is also likely that people who get RA have certain inherited traits (genes) that cause a disturbance in the immune system.

2.2.3 a   Age:
Rheumatoid arthritis can occur at any age, but usually begins in people between the ages of 20 and 45. This condition is more common in older people, but children also can develop juvenile rheumatoid arthritis or Still's disease.

2.2.3 b Excess Weight And Obesity:
Both obesity and rheumatoid arthritis involve hormonal changes, but it’s not fully understood how obesity affects the risk of autoimmune diseases
Excess weight also strains joints and may contribute to the breakdown of joint tissue during rheumatoid arthritis. People who are overweight also have an increased risk for other kinds of arthritis.

2.2.3 c Occupation:
Occupation might influence whether a person develops rheumatoid arthritis and how far it progresses. Rheumatoid arthritis is more likely to lead to disability in people who work in assembly or installation

2.2.3 d   Injuries and Diseases:
Serious knee injuries can damage cartilage and add to the problem of joint damage during arthritis. However, no connection has been shown between previous injury and the immune system changes of rheumatoid arthritis

2.2.3 e   Race and Ethnicity:
People around the world of all races and ethnicities can have rheumatoid arthritis. In the U.S., preliminary research suggests that one of the genes that increase susceptibility to the disease occurs slightly more often in Caucasians than in African Americans.

2.2.3 f   Smoking:
Smoking may be associated with rheumatoid arthritis.  People who smoked are more likely to have this disease.

2.2.3. g   Genetics:
People with a family history of rheumatoid arthritis are more likely to develop it and susceptibility to this disease has been traced to specific genes. However, other factors are important and some people who are predisposed genetically do not have rheumatoid arthritis.

2.2.3. h   Gender:
Women are more likely to have rheumatoid arthritis than men are. They also have a higher risk of developing the more severe (type 2) form of the disease. Different sources estimate that two to four times as many women have rheumatoid arthritis as men.

2.2.3.  I   Breastfeeding Helps To Avoid Rheumatoid Arthritis:
Breastfeeding lowers a woman's risk for rheumatoid arthritis. The risk is cut in half among women who breastfeed for two years or more.Female sex hormones have long been thought to play a role in rheumatoid arthritis, which is diagnosed in women up to four times as often as in men. Rheumatoid arthritis often develops when hormone levels are changing, such as in the first few months after giving birth and around the time of menopause.

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3.1  Diagnosis of Rheumatoid Arthritis: ⁴
It often is difficult to rule out alternate causes of joint pain during the early stages of rheumatoid arthritis. A diagnosis is based on the symptoms, our medical history, and a physical examination. An X- ray, a blood test for rheumatoid factor and other laboratory tests also may help our doctor to distinguish between other conditions and rheumatoid arthritis.

3.2 Rheumatoid Arthritis SeekingProfessional Help for Rheumatoid Arthritis Pain:

3.2.1 When To See A Doctor: -
As we get older, many of us will feel occasional joint pain or discomfort that comes and goes. This does not usually require professional treatment. But we should see a doctor if: -

1. We regularly have morning stiffness in our joints.
2. We experience persistent joint pain that does not improve with self-care.
3. The joint pain is increasing.
4. The joint is swollen, red, hot or tender to the touch.
5. It is difficult to move without pain.
6. We also have a fever.
7. Several joints on the left and right sides of your body are affected.

3.2.2 Examination of disease:⁷
There are many sources of joint pain, and in early rheumatoid arthritis it is often difficult to rule out other causes of your symptoms. Our doctor will try to determine the causes of

our symptoms based on our description, our medical history, and a physical examination. They also may use X- rays and laboratory tests to distinguish between other conditions and rheumatoid arthritis. A blood test can be done for rheumatoid factor, which is present in 80% of people with rheumatoid arthritis, but it may not be visible early on.

The initial examination is also important in monitoring changes in our health over time. If rheumatoid arthritis is diagnosed, regular doctor visits will allow us to adjust treatments as needed.

3.2.2 a  Our Medical History:-
Our doctor is likely to begin by asking about our symptoms. Our description of when, where and how we have experienced any pain, stiffness or difficulty using our joints is very important. Be sure to let our doctor know if we have taken any medications or nutritional supplements and whether symptoms have affected our work or daily activities.

 3.2.2 b  Physical Examination:-
This includes general screening of our health to check our reflexes, muscle strength, skin and our ability to carry out daily activities. Our doctor is also likely to examine our joints and check to see if their movement is restricted.

3.2.3 c   X- rays:-
Early rheumatoid arthritis does not always appear on x- rays because bone damage is not yet visible. However, X- rays can be a useful tool for distinguishing between rheumatoid arthritis, osteoarthritis and other conditions. Early X -rays also can be used to monitor changes in the bones over time if the disease progresses.

3.2.2 d   Laboratory Tests: -
Blood tests can be used to help diagnose rheumatoid arthritis. One blood test that measures red blood cells erythrocyte sedimentation rate is likely to be higher than normal if rheumatoid arthritis is causing inflammation in your body.
A second blood test searches for "rheumatoid factor," an antibody protein produced by our immune system. Rheumatoid factor is found in 80% of people with rheumatoid arthritis. However, this protein may not be present during early stages of the disease, and some people who have rheumatoid factor do not have arthritis.

3.3 Alternative Diagnoses List For Rheumatoid Arthritis:⁷
For a diagnosis of rheumatoid arthritis, the following list of conditions has been mentioned:

• Joint trauma
• Arthritis
• Osteoarthritis
• Lyme disease
• Ankylosing spondylitis
• Parvovirus arthritis (type of Infectious arthritis)
• Gonococcal arthritis (type of Infectious arthritis)
• Psoriatic arthritis
• Bacterial joint infection
• Viral joint infection
• Inflammatory bowel disease
• Dermatomyositis
• Cancer (some forms).

3.5   Rheumatoid Arthritis As An Alternative Diagnosis: -
The other diseases for which rheumatoid arthritis is listed as a possible alternative diagnosis are following:

• Ankylosing Spondylitis
• Fibromyalgia
• Osteoarthritis
• Polymyalgia rheumatica
• Psoriasis
• Reiter’s syndrome
• Sarcoidosis
• Spondylitis

4.1 Rheumatoid Arthritis Drug Treatments:^4,5
Drug treatments for rheumatoid arthritis can be divided into two categories, those that treat the symptoms of pain and inflammation and the more aggressive drugs that slow the progression of rheumatoid arthritis. Our medical treatment may start with either kind of drug or a combination of both depending on how severe our condition is.Medications that treat acute rheumatoid arthritis symptoms but are not used for long-term care include corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs).
Medications that slow rheumatoid arthritis are called disease modifying antirheumatic drugs (DMARDs). This category includes a wide range of unrelated drugs that affect the body's immune system. They are effective against rheumatoid arthritis, but also cause many serious side effects because they weaken the body's defenses.Standard medical treatment of rheumatoid arthritis includes physical therapy for improvements in joints mobility and assistance in relieve pain.  Physical activity is also critical for weight control.  Lowering one's weight is important to lessen the stress on joints, especially those found in the lower extremities. For persons suffering from severely damaged joints, joint replacement may be recommended. Common pain relievers, such as aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), are also prescribed to relieve pain and inflammation.For more severe cases, corticosteroid anti-inflammatory drugs, disease modifying antirheumatic drugs (DMARDS-including methotrexate, gold, sulfasalazine, or chloroquine), and COX-2-specific inhibitors (e.g., Vioxx and Celebrex) may be used to prevent joint destruction. However, long-term use of these drugs may have potentially severe side effects.

4.2 Treatment list for Rheumatoid Arthritis:^4,5

1. NSAIDs

• Aspirin - though not recommended for children due to side effects and the risk of Reye's syndrome.
• Salicylate medications
• Buffered aspirin
• Ibuprofen (Advil, Motrin IB)
• Ketoprofen (Orudis)
• Naproxen (Naprosyn)
• NSAID COX-2 inhibitors
  • Celecoxib (Celebrex)
  • Rofecoxib (Vioxx)

3. Disease-modifying antirheumatic drugs (DMARDs)

• Gold salts (Myochrysine, Ridaura) - oral or injected
• Antimalarials
• Hydroxychloroquine (Plaquenil)
• Penicillamine (Cuprimine, Depen)
• Sulfasalazine (Azulfidine)

     4.Immunosuppresssive medications

• Methotrexate (Rheumatrex)
• Azathioprine (Imuran)
• Cyclosporine (Sandimmune, Neoral)
• Lefluomide (Arava)

5. Corticosteroids (glucocorticoids)

• Prednisone (Deltasone, Orasone)
• Methylprednisolone (Medrol)

6. Biologic Response Modifiers

• Etanercept (Enbrel)
• IL-1 blocker

7. Antibody blood filtering - for severe rheumatoid arthritis.

8. Surgery

• Tendon reconstruction
• Synovectomy
• Surgical joint realignment
• Surgical joint replacement

9. Lifestyle treatments

• Rest
• Exercise
• Adequate nutrition
• Joint care
• Joint splinting
• Avoid alcohol

10. Rehabilitation treatments

• Splinting of the hands
• Physiotherapy
• Occupational therapy
• Mobility aids

11. Stress relief

• Rest
• Exercise
• Relaxation therapy                        
•  Biofeedback
• Biofeedback

 4.1.2 Newer Rheumatoid Arthritis Drugs:^4-6

Arthritis treatments aim to relieve pain, reduce inflammation and slow or stop joint damage to maintain or restore the patient's functional ability and quality of life. Arthritis therapies generally used today address the medical needs of many patients. However, these therapies are occasionally associated with harmful side effects ranging from mild to severe. Medical research continues to search for effective, fast-acting treatments with fewer side effects.

New arthritis drugs designed to meet these treatment needs are presently available or awaiting approval by the U.S. Food and Drug Administration (FDA). The foundation for these new drugs was laid in basic biomedical research supported by the National Institutes of Health.

1. Biological Response Modifiers for Rheumatoid Arthritis

One class of drugs in this category reduces inflammation in the joints by blocking the action of a substance called tumor necrosis factor (TNF). TNF is a protein of the body's immune system that triggers inflammation during normal immune responses; however, when overproduced, TNF can lead to excessive inflammation such as that experienced by patients with rheumatoid arthritis.

Enbrel® (etanercept)-
Twice-weekly subcutaneous (under the skin) injections by the patient or health care provider
Most common side effects: Mild to moderate injection-site reactions (itching, pain, swelling)
 Drug status:approved by the FDA; not recommended for patients with active infections; caution should be used in patients with a history of infections or those who develop new infections while taking Enbrel®; not recommended for pregnant women.

Remicade® (infliximab)-
How taken:intravenous (in the vein) injections by the health care provider once every 8 weeks
Most common side effects: mild infusion reactions
Drug status:approved by the FDA for use in combination with methotrexate; not recommended for pregnant women

2. Disease modifying drugs.

Arava® (leflunomide)
How taken:orally, once daily
Most common side effects: diarrhea, hair loss, rash
Drug status: Approved by the FDA; not recommended for pregnant women

3. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
COX-2 inhibitors, like traditional NSAIDs, block COX-2, an enzyme in the body known to stimulate an inflammatory response. Unlike traditional NSAIDs, however, they do not block the action of COX-1, an enzyme known to protect the stomach lining. Therefore, drugs in this category reduce joint pain and inflammation with reduced risk of gastrointestinal ulceration and bleeding.

Celebrex® (celecoxib)
How taken: Orally once or twice daily, dosage determined by the physician
Most common side effects:Abdominal pain, nausea, indigestion, diarrhea
Drug status: Approved by the FDA

Vioxx® (rofecoxib)
For rheumatoid arthritis and osteoarthritis, as well as acute pain associated with primary dysmenorrhea (painful menstruation) and postsurgical pain
How taken: Orally, once daily
Most common side effects: Abdominal pain, diarrhea, indigestion, insomnia, edema
Drug status:Approved by the FDA

4. Other Products

Hyalgan® (hyaluronan)
Hyaluronic acid viscosupplementation products for osteoarthritis. These products mimic a naturally occurring substance in the body called hyaluronic acid by providing lubrication to the knee joint, thus permitting flexible joint movement without pain.
How taken:A series of five injections per knee by a health care provider over 4 weeks
Most common side effects: Some pain and swelling at the injection site
Drug status: Approved by the FDA

Synvisc® (hylan G-F20)
How taken: A series of three injections per knee by a health care provider over a 15-day period
Most common side effects:Some pain and swelling at the injection site
Drug status: Approved by the FDA

Prosorba Column® (apheresis)
Description:Blood filtering device for severe rheumatoid arthritis. This device is designed to remove harmful antibodies from the patient's immune system, thus lowering disease activity associated with severe rheumatoid arthritis.
How used: The device consists of a catheter, tubing, and a column. The catheter and tubing are used to filter the patient's blood through the column (which is coated with protein A, a substance that attracts harmful antibodies), then reinfuse it into the patient's body. The procedure takes 2 hours and is performed weekly at a health care facility for 12 weeks.
Most common side effects:Flu-like symptoms (chills, fever, nausea, and joint/muscle pain)
Drug status:Approved by the FDA

4.3 Rheumatoid Arthritis LocalTreatments:⁷

4.3.1 Application of Heat or Cold: -
Heat applied to the aching joint often eases the pain and muscle tension of rheumatoid arthritis. Choose heat sources that gently warm our muscles, such as a hot shower or bath, hot water bottles, electric heating pads or heat lamps. To prevent burns, check our skin periodically and be careful not to fall asleep while applying heat.
Cold can be applied to reduce inflammation or relax muscle spasms. Wrap an ice bag in a towel, rather than applying ice directly to the skin. Neither heat nor cold should be applied if we have poor circulation or numbness

4.3.2 Ointments, Creams and Rubs
Capsaicin or counterirritant ointments that increase the blood flow in the skin can have soothing effects similar to applying heat

4.3.2 a Capsaicin Ointments
Capsaicin ointments contain extract of red chili peppers from the Jalapeno pepper plant. These extracts are rich in capsaicin, a substance that makes peppers burning hot. Capsaicin increases the release of, and then depletes, a messenger substance that transmits pain signals to the brain
Capsaicin ointments, such as Zostrix®, are typically applied to the skin directly over the painful joints two to four times per day.For the first few days of use, capsaicin ointment will cause a burning sensation where it is applied. The burning sensation may increase when using warm water (i.e., in a bath or shower), when the cream is applied less than three or four times per day, when there is perspiration or when a bandage is used over the cream.
It is extremely important to handle capsaicin ointments carefully and to wash our hands thoroughly after each application to avoid spreading the cream onto sensitive areas. If capsaicin comes into contact with wounds, the mouth, the nose, or other mucosal surfaces it causes very severe pain but does not cause damage

4.3.2 b Counter irritant Ointments: -
Counter irritation is the pain-relieving effect achieved by causing less severe pain to counter more intense pain. Counterirritant ointments are applied to the skin over painful joints to produce a mild local inflammatory reaction and sensations of heat or cold. This may relieve the deeper-seated joint pain. Active ingredients may include aromatic oils such as menthol, peppermint, clove and camphor oils. There is little evidence on the effectiveness of counter irritant preparations. Counterirritant ointments are available over the counter. An example is Tiger Balm. Counterirritants should not be used with other topical ointments or creams or on open wounds. Some people may be hypersensitive to one or more of the ingredients.

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4.4 Rheumatoid Arthritis Medications: -

4.4.1 Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in relieving pain in rheumatoid arthritis The best-known NSAID is aspirin. As with aspirin, the side effects of other NSAIDs are potentially severe when taken at the elevated doses that are necessary to control rheumatoid arthritis pain. Therefore, NSAIDs usually are not recommended as the first medications to take for rheumatoid arthritis. Most experts suggest that acetaminophen be taken first.

4.4.1. a  When NSAIDs Should Be Used
When lifestyle and self-help measures, topical ointments, and acetaminophen are not able to control pain, NSAIDs are typically used as the next line of defense against rheumatoid arthritis. For people who suffer from rheumatoid arthritis pain and do need NSAIDs, it is important to understand the side effects involved and the ways in which the risk of these side effects can be reduced.

4.4.1. b   Effectiveness of NSAIDs
There are some reports that NSAIDs vary in their ability to combat pain and inflammation caused by rheumatoid arthritis, but these differences may be due to the various doses that are used in investigations. There is no evidence that one drug is consistently better than another because no differences in efficacy between NSAIDs are evident, specific NSAID medications should be selected based on safety, how well they are tolerated and cost.

4.4.1. c  NSAIDs Side Effects: -
Ulcers and Bleeding-
In many people, NSAIDs increase the risk of ulcers and bleeding in the stomach and upper small intestine (duodenum). The higher the dose, the greater the risk that the drugs will cause a hole in the walls of the stomach or small intestine-a condition that is a serious medical emergency and can be fatal. Some estimates put the number of hospital admissions due to gastrointestinal side effects of NSAIDs at more than 100,000 per year.

Blood Pressure Increase
Long-term treatment with NSAIDs can raise blood pressure. This may be troublesome for people with already elevated blood pressure or other risk factors for coronary heart disease that it increase is 5 mmHg

Salt and Water Retention
Long-term use of NSAIDs can lead to retention of salt and water in the body. In people who are at risk of congestive heart failure, this can become troublesome.

Impairment of Kidney Function
NSAIDs can cause impairment of blood flow in the kidneys, especially in older people. This problem will go away once the drug is no longer taken.

Interference with Blood Coagulation
Because NSAIDs interfere with the clotting function of blood platelets, their use can prolong bleeding time and make it more difficult to stop bleeding. This may be a problem for people who take blood thinners. Fortunately, there are nonacetylated NSAIDs, such as salsalate, which do not interfere with blood clotting.

4.4.1. d   NSAIDs with the Least Side Effects: -
People differ in how they react to drugs and it is not possible to predict with certainty how a drug will affect any given person. Several studies have compared NSAIDs in terms of the likelihood that they will cause bleeding and ulcers in the stomach and small intestine. Among the safest NSAIDs are salsalate, fenoprofen and low-dose ibuprofen. Among the least safe appear to be ketoprofen, indomethacin and piroxicam.

4.4.2 COX-2 Inhibitors
Recently, so-called super aspirins have received much attention. These drugs are a new kind of NSAID, technically known as COX-2 inhibitors. Two COX-2 inhibitors, celecoxib (Celebrex®) and rofecoxib (Vioxx®), have been approved for treating rheumatoid arthritis. As with traditional NSAIDs, COX-2 inhibitors relieve pain, lower fever and reduce inflammation. Unlike traditional NSAIDs, COX-2 inhibitors interfere less with the protective roles of COX-1 in the stomach, intestine, kidneys, and other tissues and may cause fewer side effects as a result.
Anyone who is allergic to sulfa drugs, aspirin or other NSAIDs may experience an allergy to COX-2 inhibitors. But now cox-2 inhibitor rofecoxib is prohibited.

4.4.3  How COX-2 Inhibitors Differ from Other NSAIDs^4,5,7
Aspirin and other NSAIDs inhibit the production of messenger substances called prostaglandins that are involved in inflammation tissue repair and maintenance, pain and other important functions. Prostaglandins are made from certain polyunsaturated fatty acids in the presence of an enzyme called cyclo-oxygenase or COX. There are two known forms of the enzyme cyclo-oxygenase, COX-1 and COX-2, which have different distributions and functions in the body.
Standard NSAIDs such as aspirin inhibit both COX-1 and COX-2, while the new NSAIDs inhibit COX-2 about 100 times more strongly than COX-1. Even more strongly selective COX-2 inhibitors are under development.

4.4.4 Effectiveness of COX-2 Inhibitors vs. Older NSAIDs
COX-2 inhibitors relieve rheumatoid arthritis pain as well as standard NSAIDs. The efficacy and side effects of COX-2 inhibitors to the use of conventional NSAIDs with a compound to protect the gastrointestinal tract. Both treatments were equally effective and safer than standard NSAIDs taken alone.
Use of COX-2 inhibitors with rheumatoid arthritis and osteoarthritis suggests that they treat acute pain as effectively as standard NSAIDs.

4.4.5 Corticosteroids
Corticosteroids, also known as steroids, are used often for acute pain and inflammation because they provide quick relief. They also are used to slow joint damage during early stages of rheumatoid arthritis.
Corticosteroids are available in different forms. Oral steroids often are combined with DMARDs and have sometimes been used for people who experience severe side effects from NSAIDs. Injections can relieve acute flare-ups of particular joints, but only three to four injections per year are considered safe. Injections also are used for rheumatoid arthritis in children in place of oral medications. Finally, intravenous steroids may be applied as an alternative to DMARDs.

4.4.5 a  Corticosteroid Side Effects
Long-term use of corticosteroids can cause severe side effects and make withdrawal difficult. Side effects may include high blood pressure, infections, cataracts, glaucoma, diabetes, psychosis and osteoporosis. Additional side effects that may cause concern include weight gain and fluid retention, irregular menstruation, acne, excess hair, bruising easily, irritability and insomnia.

4.4.6  Disease Modifying Antirheumatic Drugs (DMARDs)
Medications that slow the progression of rheumatoid arthritis are called disease modifying antirheumatic drugs (DMARDs). These drugs are used to prevent damage to joints and limit development of rheumatoid arthritis. DMARDs have a delayed effect and may be used in combination with drugs that address immediate pain and inflammation such as NSAIDs or corticosteroids.
Early, aggressive treatment with DMARDs has sometimes been effective in slowing the progress of rheumatoid arthritis and also might prevent damage to the heart and other tissue. Over time the effectiveness of these drugs decreases while the risk of serious side effects increases.  DMARDs are a broad category that includes a wide range of different drugs that also have been used for other conditions. Different kinds of DMARDs include tumor necrosis factor (TNF) blockers, other biologic response modifiers and immunosuppressants.

4.4.7  DMARDs vs. NSAIDs
Depending on what kind of rheumatoid arthritis we have and whether it is expected to progress, our treatment may begin with either DMARDs or NSAIDs. When compared to NSAIDs, DMARDs are stronger but have more side effects. Most DMARDs are deleterious to the stomach and intestine. Serious complications are comparable to those for long-term use of NSAIDs but are rare.Examples of the most commonly used DMARDs include methotrexate (Rheumatrex, Trexall), hydroxychloroquine (Plaquenil), leflunomide (Arava), the auranofin (Ridaura) and other compounds containing gold, sulfasalazine (Azulfidine, Azulfidine EN-Tabs) and minocycline (Dynacin, Minocin).

4.4.8  Biologic Response Modifiers
Biologic response modifiers are DMARDs that have been engineered to modify the body's inflammatory response. They work by targeting specific proteins that contribute to inflammation during rheumatoid arthritis. This specificity means that they are less harmful than immunosuppressants that weaken the entire immune system and leave the body vulnerable to ordinary infections.Several tumor necrosis factor (TNF) blockers and one interleukin-1 blocker are approved for use in moderate and severe stages of rheumatoid arthritis. These kinds of drugs are named for the inflammatory proteins they target. Additional drugs that block different inflammation-causing proteins are currently under development.

4.4.8  a  TNF Blockers: -
Tumor necrosis factor (TNF) blockers are biologic response modifiers used to treat moderate to severe rheumatoid arthritis. Two TNF blockers are currently in use, infliximab (Remicade) and etanercept (Enbrel), but many insurance plans do not cover them because of their high cost. Long-term side effects are not well known for TNF blockers because they are relatively new, but there is concern that they may damage nerves or increase infections. For this reason, TNF blockers may not be recommended for people with multiple sclerosis or people who carry tuberculosis.

4.4.8  b   Interleukin-1 Blockers
Only one biologic response modifier that targets the protein interleukin-1 has been approved. This protein contributes to joint inflammation and blocking it may reduce pain. Anakinra (Kineret) is delivered subcutaneously and it has worked for some patients who do not respond to standard DMARDs. Some side effects have been reported, including greater susceptibility to respiratory and other infections and headaches.

4.4.9 Immunosuppressants
Immunosuppressants are used only when other treatments are no longer effective. They have many negative side effects. Leflunomide (Arava) has fewer side effects because it acts on the immune system in a targeted way.  However, most of these drugs weaken the immune system and also may increase the risk of stomach and intestinal distress, anemia, blood problems, and some kinds of cancer. Examples of immunosuppressants include azathioprine (Imuran) and cyclosporine (Neoral, Sandimmune).

4.5 Rheumatoid Arthritis SurgicalRelief
Surgery may be considered when damage to a major joint impedes daily activity or when pain no longer responds to medication. The risks and benefits of surgery should be discussed with our doctor in light of our overall health, the condition of our joints and goals for managing rheumatoid arthritis. Only an orthopedic surgeon can determine which type of procedure is appropriate for each person.
The most common kinds of surgery used to repair deformity or disability in rheumatoid arthritis are joint replacement, tendon reconstruction and synovectomy. Other surgical procedures that may be considered include arthroscopic removal of damaged tissue, arthrodesis, osteotomy and tenosynovectomy.

4.5.1 Synovectomy
Synovectomy is the removal of the joint lining where it has been affected by rheumatoid arthritis. This may be more effective before cartilage has been destroyed or when done in combination with tendon reconstruction. Over time, inflamed tissue can grow back.
Two studies that followed the long-term results of synovectomy in rheumatoid arthritis found that after 8 or 9 years, most patients continued to experience improved joint function. However, in some cases deterioration of remaining joint tissue continued after surgery.

4.5.2 Tendon Reconstruction
Tendon reconstruction attaches a new tendon to one that has been damaged by rheumatoid arthritis. Reconstruction can improve function when a tendon has been ruptured and is most commonly used for the hands.

4.5.3 Joint Replacement
Total joint replacement, also known as joint arthroplasty, involves replacing the ends of each bone in a joint with an artificial joint. Joint replacement is the most common surgery for rheumatoid arthritis and is most commonly applied to the hips or knees.
The new joint, called a prosthesis, is made of a metal alloy and a plastic like polyethylene that can sometimes last more than 20 years. However, artificial joints are not permanent and may not be the best option for younger people.One kind of artificial joint is cemented directly to the bone and can bear weight soon after surgery. A "cementless" prosthesis is made of special material that allows the bone to grow around it and attach after several weeksComplications can occasionally result from joint replacement surgery if the artificial joint does not attach well, the bones are damaged, or the joint becomes infected. However, most artificial hips work well and many people experience significant pain relief as long as 10 years after surgery.

4.6  Rheumatoid Arthritis OtherTreatments
In addition to self-care, joint protection, local treatments and medications, other alternatives to surgery do exist. Prosorba column treatment has been found to slow the progress of rheumatoid arthritis in a significant number of patients. Other treatments that may show promise in the future include the use of low-level laser therapy and stem cell transplants.

4.6.1 Prosorba Column
Prosorba column treatment removes antibodies (specialized proteins) from our blood that add to joint inflammation. Blood from the patient is filtered through a "prosorba column" and then returned. This procedure lasts approximately two and a half hours and needs to be repeated weekly for 12 weeks.The progress of rheumatoid arthritis appears to be slowed or even stopped in some patients undergoing prosorba column treatments. Most patients feel increased joint pain for a few days and other less common side effects include fatigue, anemia, itching, fever, low blood pressure and nausea. Prosorba column treatment may not be appropriate for people with heart, blood pressure or blood-clotting conditions.

5.1 Rheumatoid Arthritis Self-Care
Many aspects of rheumatoid arthritis can be managed successfully through self-care. This includes balancing exercise and rest, eating healthy food and caring for our emotional health during stressful times. Self-care also means protecting your joints during ordinary tasks and applying local treatments rheumatoid arthritis for pain. Healthy habits can make a big difference in caring for rheumatoid arthritis and can reduce the need for medications that have serious side effects.

5.1.1 Exercise
Exercise can protect our body and make us feel better. Our doctor or physical therapist can help choose the best way to strengthen our muscles, get aerobic exercise and use the full range of motion of our joints. It's important to plan for plenty of rest between exercises, breathe deeply and use good posture while exercising. Keeping up with daily exercise even when we don't feel like it can reduce pain, improve our mood and help us get a good night's sleep. Some discomfort may be expected, but pain from our workout should not last more than an hour afterward. New or sharp pain in our joints is a sign that we should stop.

5.1.2 Nutrition
Specific foods and nutrients do not appear to control the progress of rheumatoid arthritis. Omega-3 and omega-6 fatty acids and vitamin E suggested that these might block the chemical that causes joints to become inflamed. This may explain why some people have experienced less inflammation while taking fish oil supplements and why a lower risk of rheumatoid arthritis might be associated with olive oil intake.
In addition, rheumatoid arthritis and its drug treatments can lead to the depletion of needed protein, folic acid and calcium. Women with rheumatoid arthritis have a higher

risk of osteoporosis and corticosteroids may increase this risk further. Calcium and vitamin D supplements may be beneficial in preventing osteoporosis.

5.2 Rheumatoid Arthritis JointProtection: -

5.2.1 Rest
Frequent short breaks may be necessary to reduce arthritis symptoms such as inflammation, pain, and fatigue. Exercise should be interspersed with rest periods in order to stretch and relax. However, too much rest can also be a problem - resting in bed for long periods of time weakens the heart, irritates the skin, and erodes the muscle strength needed to protect joints.When joints flare up and are extra painful and inflamed, longer and more frequent rest periods may allow us to continue exercising. If pain is increasing or sharp, or if we feel new pain, rest the affected joint immediately.

5.2.2 Splint, Brace, or Cane
Temporary rest for a specific joint can be provided by a splint, brace or cane. Doctors or physical therapists can recommend the appropriate fit and use of these supports for arthritis symptoms. Each device supports a particular joint, lessening inflammation.
In addition to allowing rest, a splint may be used to hold an unstable or deformed joint in position. Splints are most often applied to wrists and hands, but also can relieve pain and swelling in ankles and feet. Splints should be removed periodically to prevent skin irritation and to move the joint through its normal range of motion.

5.2.3 Weight Management
Maintaining a healthy weight may help us to protect aches and pains, since additional weight can strain joints throughout our body. If joint surgery is needed, it is easier and less risky to conduct surgery on a patient that has less excess weight.

5.2.4 Physiotherapy: -
Physical therapists often work with patients who have rheumatoid arthritis symptoms to improve joint function and reduce pain by education, exercise and other forms of physiotherapy led to lasting improvements in morning stiffness and other rheumatoid arthritis symptoms.

5.3 Rheumatoid Arthritis Prevention
Healthy habits such as eating well, exercising, not smoking, caring for our emotional health and maintaining a healthy weight will help us be better prepared for any disease or injury that may occur. In addition, many of the complications associated with rheumatoid arthritis are affected by our diet. More specific preventative measures cannot be developed until the causes of rheumatoid arthritis are better understood.

5.3.1 Weight Control
Keeping a healthy weight can minimize a contributing risk factor for rheumatoid arthritis. Additional weight strains joints and appears to increase the risk of many other joint problems.

5.4 ManagingRheumatoid Arthritis
The goals of treatment for rheumatoid arthritis are to slow the disease and improve patients' well being. Reducing inflammation is a primary focus in order to prevent damage to joints and preserve movement. Relieving pain from rheumatoid arthritis, minimizing side effects, and reducing costs also are important components to each patient's quality of life. The overall approach for managing rheumatoid arthritis depends on whether our condition is mild or complex and expected to last more than two years. If our rheumatoid arthritis condition is mild, less aggressive treatment will minimize negative side effects. However, if our condition appears progressive, the most potent rheumatoid arthritis medications and treatments may be applied immediately to slow the disease and prevent joint damage. A rheumatoid arthritis treatment plan is likely to include a balance of exercise and rest, therapy, local treatments and medications. Self-care at home is an important complement 'to prescription drugs, surgery and other aggressive treatments that may be necessary for advanced stages of rheumatoid arthritis.

Rheumatoid arthritis is a heterogeneous disease with manifestation ranging from mild articular symptoms to life threatening complication although they has been substantial changes in practice or the past ten years, treatment for  rheumatoid arthritis is still selected empirically.In the future as our understanding of the disease processes in   rheumatoid arthritis improve it may be possible to select treatment in relation to the pathogenesis of this disease. In the mean time patients with suspected diagnosis of   rheumatoid arthritis should be referred promptly to a specialist center where their diagnosis can be confirmed and appropriate treatment started without delay, based on a careful evaluation of efficacy and potential toxicity in the individual patient.

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3.    Genard,j.,tortora,Sandra, Reynolds,grabowski,in; Bonnie,roesh,eds “Principles of anatomy & physiology” 10th edn,Published by john wiley&sons inc.,2003 pp 267.
4. F.S.K.,barar “Essential of pharmacotherapeutics” 1st edn,S.chand&company Ltd.,NEW DELHI, 1985,(Reprint-2004), pp 129.
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