Rheumatoid arthritis (RA) is a disease in which the body’s immune system - the body’s defense system - mistakenly attacks the joints. This creates inflammation that causes the tissue that lines the inside of joints to thicken, resulting in swelling and pain and can eventually result in bone erosion and joint deformity. Sometimes Inflammation can affect other organs as well, for instance, the eyes or lungs.

Even the direct cause of rheumatoid arthritis still not identified, experts think that the disease is triggered by interaction of genetic and environmental factors results in a cascade of immune reactions, which ultimately lead to the development of synovitis, joint damage, and structural bone deformity.

Treatments for rheumatoid arthritis have improved greatly and help many of those affected with that disease. It includes a wide range of medication that used to treat pain, reduce inflammation, or even slow the progression of the disease. Disease-Modifying Anti-Rheumatic Drugs (DMARDs) are the main type used. Surgical procedure is also a choice.

Aggressive drug treatment of rheumatoid arthritis while it is still in its early stages is new and more effective recommendation to lower disease activity and achieve remission. If not treated as well, the disease may carry very serious complications. Heart, eye, and lung problems are among them.

Rheumatoid arthritis is a chronic inflammatory disease that is triggered by a faulty immune system – which normally protects its health from pathogens like bacteria and viruses – causing pain, stiffness, swelling and limited motion and function of many joints, but especially the small joints in the hands and feet. The inflammation associated with rheumatoid arthritis can damage other parts of the body as well.

Rheumatoid arthritis is an autoimmune disease. This means that certain cells of the immune system do not work properly and start attacking the tissue that lines the joint that called the synovium. This leads to thickening of it that cause swelling and pain. There are scientific evidences that certain genes, hormones and environmental factors are involved.

• Genetic factors. A specific genetic marker called the HLA shared epitope have a fivefold greater chance of developing rheumatoid arthritis than do people without the marker. Other genes connected to RA include: STAT4, TRAF1, and PTPN22.
• Environmental factors. Exposure to certain hazards may play a role in person's risk for rheumatoid arthritis. Some include smoking, air pollution, insecticides and occupational exposures to mineral oil and silica.
• Hormonal factors. Some scientists think that a variety of hormonal factors may be involved, supported by that the disease may improve during pregnancy and flare after birth. Contraceptive use may also increase a person’s likelihood of developing rheumatoid arthritis.
• Other factors. The incidence of RA is typically two to three times higher in women than men. Infectious agents such as bacteria or viruses may trigger development of the disease in a person whose genes make them more likely to get it.

A joint - the place where two bones meet - is surrounded by a capsule that protects and supports it. The joint capsule is lined with a type of tissue called synovium, which produces synovial fluid that lubricates and nourishes joint tissues. In rheumatoid arthritis, an Imbalance between pro- and anti-inflammatory activities favours the induction of an autoimmune reaction, leading white blood cells to infiltrate the synovium and cause inflammation (synovitis).

During the inflammation process, the normally thin synovium becomes thick and makes the joint swollen and sometimes warm to the touch. As rheumatoid arthritis progresses, the inflamed synovium invades and destroys 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. These effects lead to the pain and joint damage often seen in rheumatoid arthritis.

Rheumatoid arthritis has several features that make it different from other kinds of arthritis. These are:

• Pain, hotness, swelling of joints;
• Symmetrical pattern of affected joints;
• Often affecting the wrist, finger joints closest to the hand (MCPJ), knees, and toe joints closest to the feet (MTPJ).
• Sometimes affecting other joints, including the neck, shoulders, elbows, hips, and ankle;
• Fatigue and loss of energy;
• Pain and stiffness lasting for more than 30 minutes in the morning or after a long rest;
• Symptoms that last for many years;
• Variability of symptoms among people with the disease;
• Low-grade fevers, with recurrent episodes.

These symptoms may come and go. A period of increased inflammation and other symptoms is called a flare that can last for days or months. It will alternate with periods of relative remission when the swelling and pain fade or disappear.

Ongoing high levels of inflammation can cause problems throughout the body. Here of some signs and symptoms of affected body organs and systems:

• Dryness, pain, redness of the eye;
• Rheumatoid nodules -small, firm lumps under the skin covers the bony areas;
• Dryness of mouth and gum irritation or infection;
• Shortness of breath;
• damage in the nerves;
• Anemia, a lower than normal number of red blood cells.

Rheumatoid arthritis can be difficult to diagnose in its early stages as symptoms differ from person to person and may not be clear in the early stages. Also, symptoms can be similar to those of other types of arthritis and joint conditions. As a result, doctors use a variety of the following tools - besides symptoms and physical examination - to diagnose the disease and to rule out other conditions.

• Rheumatoid factor (RF) test: Rheumatoid factor is an antibody that is present eventually in the blood of most people with rheumatoid arthritis. A positive RF in a person who has consistent symptoms with those of rheumatoid arthritis can be useful in confirming a diagnosis. However, not all people with rheumatoid arthritis test positive for RF, and some people test positive for rheumatoid factor, yet never develop the disease.
• Anti-cyclic citrullinated peptide (CCP) test: 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, the results are very useful in confirming a rheumatoid arthritis diagnosis.
• Other blood tests: common laboratory tests that may also done include a white blood cell count, a blood test for anemia, which is common in rheumatoid arthritis; the erythrocyte sedimentation rate (ESR), 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.
• Imaging tests. X-rays MRI and ultrasound imaging are used to determine the degree of joint destruction. They may be utilized to rule out other causes of joint pain. They may also be used later to monitor the progression 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. The goals for RA treatment may include:

• Relieve pain;
• Reduce inflammation;
• Slow down or stop joint damage;
• Improve a person’s sense of well-being and ability to function;
• Reduce long-term complications.

It is important to treat rheumatoid arthritis as soon as possible, as people who receive early, aggressive treatment for RA feel better sooner and more often, and are more likely to lead an active life. They also are less likely to have the type of joint damage that leads to joint replacement. Treatment include:

• Medications: There are different drugs used in the treatment of rheumatoid arthritis. Some are used primarily to ease the symptoms of RA; others are used to slow or stop the course of the disease and to inhibit structural damage. This include:
  • Nonsteroidal anti-inflammatory drugs (NSAIDs). Considered the least potent drugs used for RA, they are used to help ease pain by reducing inflammation, but they do not affect the course of the disease. NSAIDs include such drugs as ibuprofen, diclofenac and naproxen. For people who have had or are at risk of gastric ulcers, the doctor may prescribe celecoxib, a type of NSAID called a COX-2 inhibitor, which is designed to be safer for the stomach. NSAIDS may also carry a risk for heart, liver and kidney, especially if not taken wisely.
  • Corticosteroids. Including prednisone, prednisolone and methylprednisolone, corticosteroids 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 and low dose as possible.
  • Disease-modifying antirheumatic drugs (DMARDs). Drugs that work to modify the course of the disease and considered the standard treatments for RA. Traditional DMARDs include methotrexate, hydroxycholorquine, sulfasalazine, cyclophosphamide and azathioprine. Unfortunately, all DMARDs tend to lose effectiveness over time. Patients rarely use one drug for more than 2 years. Combining DMARDs with each other or with other types of drugs offers the best approach for many patients. All DMARDs may produce stomach and intestinal side effects, and, over the long term, each poses some risk for rare but serious reactions.
  • Biologic agents. The latest advance in the treatment of RA is proteins come from human genes that are engineered to target specific molecules on immune system cells (specifically cytokines) that play an important role in the autoimmune response involved in RA rather than acting on the immune system as a whole. These treatments also fall under the category of (DMARDs) because they can modify the disease course in RA and slow or prevent damage to joints and related structures. Tofacitinib and ruxolitinib are approved drugs of this class.
• Surgery: If medications fail to prevent or slow joint damage, the doctor and the patient may carefully consider surgery. The primary purpose of these procedures is to reduce pain, improve joint function and the patient’s ability to perform daily activities. Rheumatoid arthritis surgery may involve one or more of the following:
  • Synovectomy. Surgery to remove the inflamed synovium (lining of the joint). Synovectomy can be performed on knees, elbows, wrists, fingers and hips.
  • Tendon repair. Inflammation and joint damage may cause tendons around the joint to loosen or rupture. The surgeon may be able to repair the tendons by sewing the torn ends of the tendon together.
  • Joint fusion. Surgically fusing may be recommended to stabilize or realign a joint and for pain relief when a joint replacement isn't an option.
  • Total joint replacement. During this procedure, the surgeon removes the damaged parts of the joint and inserts a prosthesis made of metal and plastic.
• Alternative and complementary therapies: Special diets, vitamin supplements, and other alternative approaches have been suggested for treating rheumatoid arthritis. Research shows that some of these, for example, fish oil supplements primrose, borage and black currant seeds, may help reduce arthritis inflammation. For most, however, controlled scientific studies either have not been conducted on them or have found no definite benefit to these therapies. As with any therapy, patients should discuss the benefits and drawbacks with their doctors before beginning an alternative or new type of therapy.
• Activity level: People with rheumatoid arthritis need a good balance between rest and exercise, with more rest when the disease is active and more exercise when it is not. Rest helps to reduce active joint inflammation and pain and to fight fatigue. The length of time for rest will vary from person to person, but in general, shorter rest breaks every now and then are more helpful than long times spent in bed. Exercise is important for maintaining healthy and strong muscles, preserving joint mobility, and maintaining flexibility. Exercise can also help people sleep well, reduce pain, maintain a positive attitude, and manage weight. Performing low-impact aerobic exercises, such as walking, and exercises to boost muscle strength may improve overall health and reduce pressure on the joints. Exercise programs should take into account the person’s physical abilities, limitations, and changing needs.

Rheumatoid arthritis can put the patient at a higher risk of developing other conditions, particularly if it's not well controlled. These include:

• Eye Problems. The inflammatory response with RA tends to affect collagen, which makes the main component of sclera and cornea. This can lead to eye dryness and can result in corneal damage and inflammation of the sclera, which can cause redness and pain.
• Infections. Patients with RA have a higher risk for infections, both because of the disease itself and the immune-suppressing drugs used to treat it. Before starting treatment with DMARDs, patients should receive age-appropriate vaccinations for pneumococcus, influenza, hepatitis B, human papillomavirus, and varicella zoster virus.
• Skin Problems. Skin is commonly affected with RA, particularly on the fingers and under the nails. Some patients develop severe skin complications that include rash, ulcers, blisters, lumps or nodules under the skin. In general, severe skin involvement reflects a more serious form of RA.
• Lung Disease. Patients with RA are susceptible to chronic lung diseases, including interstitial fibrosis, pulmonary hypertension, and other problems.
• Vasculitis. An inflammation in the small blood vessels that can affect many organs in the body. Manifestations of vasculitis include mouth ulcers, nerve disorders, inflammation of coronary arteries and those supplying blood to the intestines.
• Cardiovascular Diseases. Patients with RA have an increased risk for heart and circulatory conditions including coronary artery disease, heart attack, atrial fibrillation and stroke. They may also face higher risks for venous thromboembolism (VTE), a condition that includes formation of blood clots in the veins that travel to the lungs and cause arterial blockage.
• Lymphoma. Patients with RA are more likely to develop non-Hodgkin's lymphoma. The low-grade inflammation in RA may play a role in the development of this cancer. Anti-TNF drugs (a sub group of DMARDs) used for RA treatment may also increase the risk for lymphoma (particularly in children and adolescents) as well as leukemia and other malignancies.
• Anemia. Anemia of inflammation and chronic disease (AI/ACD) is a type of anemia that commonly occurs with chronic, or long term, illnesses or infections. Inflammatory diseases, such as RA interfere with the body’s ability to use stored iron and respond for red blood cells production signals, which may decrease number of effective cells.
• Periodontal Disease. For People with RA, the gum and bone around the teeth are more prone be damaged by periodontal disease. This condition complicates the risk of cardiovascular diseases.
• Joint deformity. If RA goes untreated for two years, the majority of patients will develop joint erosion, indicating disease progression. Over time, rheumatoid arthritis can cause joints to deform and shift out of place.
• Carpal tunnel syndrome. a common condition in people with rheumatoid arthritis that result of compression of the median nerve that controls sensation and movement in the hands and can cause symptoms such as aching, numbness and tingling in the thumb, fingers and part of the hand.
• Emotional problem. The effects of rheumatoid arthritis are not just physical. Many people with RA also experience related psychological issues, such as depression, anxiety and low self-esteem. Rheumatoid arthritis can affect virtually every area of a person’s life including work, study, joy and family life.

There is no known way to prevent Rheumatoid arthritis, because the exact causes are still unknown. However, there may be ways to reduce the chance of having that disease by controlling modifiable risk factors. Another chance is available to prevent developing severe joint damage in case of having RA. From these preventive measures:

• Quit smoking. Smoking is the strongest and most consistent modifiable risk factor for RA, particularly for people who are anti CCP positive. Avoiding that bad behavior may protect the joint from damage.
• Early treatment: Treating RA as early as possible could save the joint from unwanted damage. Some believe strongly in prescribing an aggressive regimen of RA drugs in the early stage are more helpful.

Rheumatoid arthritis is chronic in most cases, 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. Scientists now believe that it begins to damage bones during the first year or two that a person has the disease, which is one reason why early diagnosis and treatment are so important.

The disease can vary widely in consequences and outcomes. The outlook has greatly improved for many people with early, aggressive treatment. More effective control of RA will not only improve quality of life, but also improve life expectancy in patients. However, RA remains a serious disease that can lead to disability and mortality.

A Disease Activity Score (DAS) is used to determine whether Rheumatoid arthritis is under control and if any treatment adjustments are required. It can also assist in establishing a target score to aim for, to help inform treatment decisions and optimize disease management. DAS28 is a composite outcome measure that assesses many disease manifestations like joint tenderness and swelling, degree of inflammation (ESR rate or CRP test), and the patient’s Visual Analogue Score.    The results are combined to produce the DAS28 score, as discussed in the next table:

The annual incidence of Rheumatoid arthritis worldwide is approximately 3 cases per 10,000 population, and the prevalence rate is nearly 1%, increasing with age and peaking between the ages of 35 and 50 years. RA affects all populations, though it is much more prevalent in some groups such as Native American and much less prevalent in black people. First-degree relatives of individuals with RA are at 2- to 3-fold higher risk for the disease.

Rheumatoid arthritis is the most common type of autoimmune arthritis. The disease is more common in women and in developed countries, where RA is a leading cause of chronic morbidity among them. Within 10 years on onset, at least 50% of patients in developed countries are unable to hold down a full-time job.