Rheumatoid Arthritis (RA) is an inflammatory disease that causes pain, swelling, stiffness, and loss of function in the joints. It occurs when the immune system, which normally defends the body from invading organisms, turns its attack against the membrane lining the joints. This creates inflammation that causes the tissue that lines the inside of joints (the synovium) to thicken, resulting in swelling and pain in and around the joints.

Joints can become loose, unstable, painful and lose their mobility, Joint deformity also can occur.

Joint damage cannot be reversed, and because it can occur early, doctors recommend early diagnosis and aggressive treatment to control RA.

Rheumatoid arthritis most commonly affects the joints of the hands, feet, wrists, elbows, knees and ankles.

Rheumatoid Arthritis has several features that make it different from other kinds of arthritis. For example, Rheumatoid Arthritis generally occurs in a symmetrical pattern, meaning that if one knee or hand is involved, the other one also is. The disease often affects the wrist joints and the finger joints closest to the hand. It can also affect other parts of the body besides the joints. In addition, people with Rheumatoid Arthritis may have fatigue, occasional fevers, and a loss of energy.

The course of rheumatoid arthritis can range from mild to severe. In most cases it is chronic, meaning it lasts a long time—often a lifetime. For many people, periods of relatively mild disease activity are punctuated by flares, or times of heightened disease activity. In others, symptoms are constant.

Because RA also can affect body systems, such as the cardiovascular or respiratory systems, it is called a systemic disease. Systemic means “entire body.” 

In a healthy person, the body’s immune system detects invaders, such as bacteria and viruses, and sends chemicals to fight them. The body sends one set of chemicals to start the attack and another to stop it. That is what’s called the immune response, and it is normally well controlled. RA is an autoimmune disease, which means the immune system mistakes the body’s cells for foreign invaders and repeatedly attacks healthy tissues. White blood cells are sent to the synovium– the tissue that lines the insides of the joints and produces synovial fluid, a clear substance that lubricates the joint and helps it move smoothly. The inflammatory process causes the synovium to thicken, making the joint feel puffy and swollen. If inflammation goes unchecked, it can damage cartilage, the elastic tissue that covers the ends of bones in a joint, as well as the bones themselves. Over time, there is loss of cartilage, and the joint spacing between bones can become smaller. Joints can become loose, unstable, painful and lose their mobility. Joint deformity can occur too. Joint damage cannot be reversed

Scientists still do not know exactly what causes the immune system to turn against the body’s own tissues in Rheumatoid Arthritis, but research over the last few years has begun to piece together the factors involved.

Genetic (inherited) factors : Scientists have discovered that certain genes known to play a role in the immune system are associated with a tendency to develop Rheumatoid Arthritis. For the genes that have been linked to Rheumatoid Arthritis, the frequency of the risky gene is only modestly higher in those with Rheumatoid Arthritis compared with healthy controls. What is clear, however, is that more than one gene is involved in determining whether a person develops Rheumatoid Arthritis and how severe the disease will become. Researchers have shown that people with a specific genetic marker called the HLA shared epitope have a fivefold greater chance of developing Rheumatoid Arthritis than do people without the marker.

The HLA genetic site controls immune responses. Other genes connected to RA include: STAT4, a gene that plays important roles in the regulation and activation of the immune system; TRAF1 and C5, two genes relevant to chronic inflammation; and PTPN22, a gene associated with both the development and progression of Rheumatoid Arthritis. Yet not all people with these genes develop RA and not all people with the condition have these genes.

Environmental factors : Many scientists think that something must occur to trigger the disease process in people whose genetic makeup makes them susceptible to Rheumatoid Arthritis. Although uncertain and poorly understood, some exposures such as asbestos or silica may increase the risk for developing Rheumatoid Arthritis.

Other factors : Some scientists also think that a variety of hormonal factors may be involved. Women are more likely to develop Rheumatoid Arthritis than men. The disease may improve during pregnancy and flare after pregnancy. Breastfeeding may also aggravate the disease. Contraceptive use may increase a person’s likelihood of developing Rheumatoid Arthritis. This suggests hormones, or possibly deficiencies or changes in certain 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 are not known, one thing is certain: Rheumatoid Arthritis develops as a result of an interaction of many factors. Researchers are trying to understand these factors and how they work together.

Rheumatoid Arthritis can be difficult to diagnose in its early stages for several reasons. First, there is no single test for the disease. In addition, symptoms differ from person to person and can be more severe in some people than in others. Also, symptoms can be similar to those of other types of arthritis and joint conditions, and it may take some time for other conditions to be ruled out. Finally, the full range of symptoms develops over time, and only a few symptoms may be present in the early stages. A primary care physician may suspect RA based in part on a person's signs and symptoms. If so, the patient will be referred to a rheumatologist – a specialist with specific training and skills to diagnose and treat RA.

Rheumatologists use a variety of the following tools to diagnose the disease and to rule out other conditions:

Medical history : The doctor begins by asking the patient to describe the symptoms, and when and how the condition started, as well as how the symptoms have changed over time. The doctor will also ask about any other medical problems the patient and close family members have and about any medications the patient is taking. Accurate answers to these questions can help the doctor make a diagnosis and understand the impact the disease has on the patient’s life.

Physical examination : The doctor will check the patient’s reflexes and general health, including muscle strength. The doctor will also examine bothersome joints and observe the patient’s ability to walk, bend, and carry out activities of daily living. The doctor will also look at the skin for a rash and listen to the chest for signs of inflammation in the lungs.

Laboratory tests : Several lab tests may be useful in confirming a diagnosis of Rheumatoid Arthritis. Following are some of the more common ones:

a. Rheumatoid factor (RF) : Rheumatoid factor is an antibody that is present eventually in the blood of most people with Rheumatoid Arthritis. (An antibody is a special protein made by the immune system that normally helps fight foreign substances in the body.) Not all people with Rheumatoid Arthritis test positive for rheumatoid factor, and some people test positive for rheumatoid factor, yet never develop the disease. Rheumatoid factor also can be positive in some other diseases; however, a positive RF in a person who has symptoms consistent with those of Rheumatoid Arthritis can be useful in confirming a diagnosis. Furthermore, high levels of rheumatoid factor are associated with more severe Rheumatoid Arthritis.

b. Anti-CCP antibodies : This blood test detects antibodies to cyclic citrullinated peptide (anti-CCP). This test is positive in most people with Rheumatoid Arthritis and can even be positive years before Rheumatoid Arthritis symptoms develop. When used with the RF, this test’s results are very useful in confirming a Rheumatoid Arthritis diagnosis.

c. Others : Other common laboratory tests include a white blood cell count, a blood test for anemia, which is common in Rheumatoid Arthritis; the erythrocyte sedimentation rate (often called the sed rate), which measures inflammation in the body; and C-reactive protein, another common test for inflammation that is useful both in making a diagnosis and monitoring disease activity and response to anti-inflammatory therapy.

d. Imaging tests : X-rays are used to determine the degree of joint destruction. They are not useful in the early stages of Rheumatoid Arthritis before bone damage is evident; however, they may be used to rule out other causes of joint pain. They may also be used later to monitor the progression of the disease. Magnetic resonance imaging (MRI) and ultrasound may be useful in identifying the early stages of Rheumatoid Arthritis and can help determine the severity of the disease.

Doctors use a variety of approaches to treat Rheumatoid Arthritis. These are used in different combinations and at different times during the course of the disease and are chosen according to the patient’s individual situation. No matter what treatment the doctor and patient choose, however, the goals are the same.

The goals of Rheumatoid Arthritis (RA) treatment are to :

• Stop inflammation (put disease in remission)
• Relieve symptoms
• Prevent joint and organ damage
• Improve physical function and overall wellbeing
• Reduce long-term complications

To meet these goals, the doctor will follow these strategies :

Early, aggressive treatment: The first strategy is to reduce or stop inflammation as quickly as possible – the earlier, the better.

Targeting remission: Doctors refer to inflammation in RA as disease activity. The ultimate goal is to stop it and achieve remission, meaning minimal or no signs or symptoms of active inflammation. One strategy to achieve this goal is called “treat to target.”

Tight control: Getting disease activity to a low level and keeping it there is what is called having “tight control of RA.” Research shows that tight control can prevent or slow the pace of joint damage.

Medications for RA

There are different drugs used in the treatment of Rheumatoid Arthritis. Some are used primarily to ease the symptoms of RA (such as pain and swelling); others are used to slow the progression of disease and to inhibit structural damage.

Drugs that Ease Symptoms

NSAIDs for Rheumatoid Arthritis are medications that reduce pain and inflammation without the use of steroids. They are available over the counter and also by prescription. NSAIDs include such drugs as ibuprofen, ketoprofen and naproxen sodium, among others. Your doctor may prescribe a proton pump inhibitor (PPI) alongside the NSAID, which will help to protect your stomach. For people who have had or are at risk of stomach ulcers, the doctor may prescribe celecoxib, a type of NSAID called a COX-2 inhibitor, which is designed to be safer for the stomach. These medicines can be taken by mouth or applied to the skin (as a patch or cream) directly to a swollen joint.

Drugs that Slow Disease Activity

Corticosteroids. Corticosteroid medications, including prednisone, prednisolone and methyprednisolone, are potent and quick-acting anti-inflammatory medications. They may be used in RA to get potentially damaging inflammation under control, while waiting for NSAIDs and DMARDs (below) to take effect. Because of the risk of side effects with these drugs, doctors prefer to use them for as short a time as possible and in doses as low as possible. You shouldn't stop taking your steroid tablets or alter the dose unless your doctor recommends it. It can be dangerous to stop steroids suddenly.

DMARDs. Disease-modifying antirheumatic drugs (called DMARDs, second-line drugs or remittive therapy) appear to slow or halt the progression of Rheumatoid Arthritis and thus work to modify the course of the disease by altering the function of your body's immune system. Traditional DMARDs include methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, cyclophosphamide and azathioprine. These medicines can be taken by mouth, be self-injected or given as an infusion in a doctor’s office. Because these drugs are slow-acting and it may be several weeks before you notice any benefit – so it's important to keep taking them even if they don't seem to be having an effect. Many of these drugs can be used in combination with each other, which increases the effectiveness.

Biologics. For patients with more significant disease, medications referred to as biologic response modifiers or “biologics” can specifically target parts of the immune system that lead to inflammation, joint and tissue damage. These drugs are a subset of DMARDs. Biological therapies tend to work a little more quickly than conventional DMARDs, though it may still be several weeks or months before you get the full benefit from them. They are either injected or given by infusion in a doctor’s office. Because they target specific steps in the inflammatory process, they don’t wipe out the entire immune response as some other RA treatments do. In many people with RA, a biologic can slow, modify or stop the disease – even when other treatments haven’t helped much.

VORTUXI (Rituximab) is biologic disease-modifying anti rheumatic drug, also called a biologic DMARD, or simply biologic which binds to CD 20 antigen which causes inflammation and tissue damage.

JAK inhibitors. A new subcategory of DMARDs known as “JAK inhibitors” block the Janus kinase, or JAK, pathways, which are involved in immune responses that trigger the joint inflammation. JAK inhibitors are effective at alleviating symptoms in moderate to severe cases of Rheumatoid Arthritis. JAK inhibitors are also taken in cases where the patient can’t tolerate traditional DMARDs. Tofacitinib belongs to this class. Unlike biologics, it can be taken by mouth.

Surgery

Most people with RA never have surgery but it can be an important option for people with permanent damage that limits daily function, mobility and independence Joint replacement surgery can relieve pain and restore function in joints badly damaged by RA. The procedure involves replacing damaged parts of a joint with metal and plastic parts. Hip and knee replacements are most common. However, ankles, shoulders, wrists, elbows, and other joints may be considered for replacement. Surgery may help restore your ability to use your joint. It can also reduce pain and correct deformities.