Rheumatoid Arthritis (RA)

What Is Rheumatoid Arthritis? Causes, Signs & Symptoms, Diagnosis, Treatment, and Prevention

What Is Rheumatoid Arthritis?

Rheumatoid arthritis, or RA, is an autoimmune and inflammatory disease, which means that your immune system attacks healthy cells in your body by mistake, causing inflammation (painful swelling) in the affected parts of the body. Unlike the wear-and-tear damage of osteoarthritis, rheumatoid arthritis affects the lining of your joints, causing a painful swelling that can eventually result in bone erosion and joint deformity.

The inflammation associated with rheumatoid arthritis is what can damage other parts of the body as well. While new types of medications have improved treatment options dramatically, severe rheumatoid arthritis can still cause physical disabilities.

Rheumatoid arthritis mainly attacks the joints, usually many joints at once. Rheumatoid arthritis commonly affects joints in the hands, wrists, and knees. In a joint with Rheumatoid arthritis, the lining of the joint becomes inflamed, causing damage to joint tissue. This tissue damage can cause long-lasting or chronic pain, unsteadiness (lack of balance), and deformity (misshapenness).

Rheumatoid arthritis can also affect other tissues throughout the body and cause problems in organs such as the lungs, heart, and eyes.

What causes Rheumatoid Arthritis?

Rheumatoid arthritis is the result of an immune response in which the body’s immune system attacks its own healthy cells. The specific causes of Rheumatoid arthritis are unknown, but some factors can increase the risk of developing the disease.

Rheumatoid arthritis develops when white blood cells, which normally protect the body from foreign invaders such as bacteria and viruses, enter the synovium (the thin tissue that lines the synovial joints). Inflammation ensues — the synovium thickens, causing swelling, redness, warmth, and pain in the synovial joint.

Over time, the inflamed synovium can damage the cartilage and bone within the joint, as well as weaken supportive muscles, ligaments, and tendons.

Researchers don't know exactly what causes the immune system to invade the synovium, but it's believed that genes and environmental factors play a role in the development of Rheumatoid arthritis.

Researchers have studied a number of genetic and environmental factors to determine if they change a person's risk of developing Rheumatoid arthritis.

Characteristics that increase risk:

→ Genetics/inherited traits. People born with specific genes are more likely to develop Rheumatoid arthritis. These genes, called HLA (human leukocyte antigen) class II genotypes, can also make your arthritis worse. A number of other genes also appear to be associated with Rheumatoid arthritis susceptibility, including STAT4, PTPN22, TRAF1-C5, PADI4, CTLA4, among others, according to a report in the journal Rheumatology. But not everyone with these identified gene variants develops Rheumatoid arthritis, and people without them can still develop it. So, it's likely that environmental factors often trigger the disease, particularly in people with a genetic makeup that makes them more susceptible to it. The risk of Rheumatoid arthritis may be highest when people with these genes are exposed to environmental factors like smoking or when a person is obese.

→ Age. Rheumatoid arthritis can begin at any age, but the likelihood increases with age. The onset of Rheumatoid arthritis is highest among adults in their sixties.

→ Gender. New cases of Rheumatoid arthritis are typically two-to-three times higher in women than men.

→ Smoking. Multiple studies show that cigarette smoking increases a person’s risk of developing Rheumatoid arthritis and can make the disease worse.

→ History of live births. Women who have never given birth may be at greater risk of developing Rheumatoid arthritis.

→ Early Life Exposures. Some early life exposures may increase risk of developing Rheumatoid arthritis in adulthood.  For example, one study found that children whose mothers smoked had double the risk of developing RA as adults. Children of lower income parents are at increased risk of developing RA as adults.

→ Obesity. Being obese can increase the risk of developing Rheumatoid arthritis. Studies examining the role of obesity also found that the more overweight a person was, the higher his or her risk of developing Rheumatoid arthritis became.

Other potential causes:

• Viruses and bacteria (though certain infections may reduce Rheumatoid arthritis risk, at least temporarily)
• Female hormones
• Exposure to certain kinds of dust and fibers
• Exposure to secondhand smoke
• Severely stressful events

Characteristics that can decrease risk:

Unlike the risk factors above which may increase risk of developing Rheumatoid arthritis, at least one characteristic may decrease risk of developing Rheumatoid arthritis.

→ Breastfeeding. Women who have breastfed their infants have a decreased risk of developing Rheumatoid arthritis.

What are the signs and symptoms of Rheumatoid Arthritis?

With Rheumatoid arthritis, there are times when symptoms get worse, known as flares, and times when symptoms get better, known as remission.

Signs and symptoms of Rheumatoid arthritis include:

→ Pain or aching in more than one joint

→ Stiffness in more than one joint

→ Tenderness and swelling in more than one joint

→ The same symptoms on both sides of the body (such as in both hands or both knees)

→ Weight loss

→ Fever

→ Fatigue or tiredness

→ Weakness

Early signs of disease, such as joint swelling, joint pain, and joint stiffness, typically begin in a gradual and subtle way, with symptoms slowly developing over a period of weeks to months and getting worse over time. 

Rheumatoid arthritis usually begins in the small bones of the hands (particularly those at the base and middle of the fingers), base of the toes, and wrists. Morning stiffness that lasts for 30 minutes or more is another hallmark symptom of Rheumatoid arthritis.

Rheumatoid arthritis is a progressive disease. When left untreated, inflammation can start to develop in other parts of the body, causing various potentially serious complications that can affect other organs, such as the heart, lungs, and nerves, and could cause significant long-term disability.

Other health effects:

→ Eyes. Dryness, pain, inflammation, redness, sensitivity to light and trouble seeing properly.

→ Mouth. Dryness and gum inflammation, irritation or infection. 

→ Skin. Rheumatoid nodules - small lumps under the skin over bony areas. 

→ Lungs. Inflammation and scarring that can lead to shortness of breath and lung disease.

→ Blood vessels. Inflammation of blood vessels that can lead to damage in the nerves, skin and other organs.

→ Blood. A lower than normal number of red blood cells. 

→ Heart. Inflammation can damage the heart muscle and the surrounding areas.

→ Body weight. Painful joints also make it hard to exercise, leading to weight gain. Being overweight may make people with Rheumatoid arthritis more likely to develop high cholesterol, diabetes, heart disease and high blood pressure.

How Is Rheumatoid Arthritis diagnosed?

Getting an accurate diagnosis as soon as possible is the first step to treating Rheumatoid arthritis effectively. A doctor with specialized training in treating arthritis (called a rheumatologist) is the best person to make a correct diagnosis, using medical history, a physical examination and lab tests.

Your Medical history:

The doctor will ask about joint symptoms (pain, tenderness, stiffness, difficulty moving), when they started, if they come and go, how severe they are, what actions make them better or worse and whether family members have Rheumatoid arthritis or another autoimmune disease. 

A Physical examination:  

The doctor will look for joint tenderness, swelling, warmth and painful or limited movement, bumps under the skin or a low-grade fever. 

Blood tests:

The blood tests look for inflammation and blood proteins (antibodies) that are linked to Rheumatoid arthritis:

→ Erythrocyte sedimentation rate (ESR, or “sed rate”) 

→ C-reactive protein (CRP)

A high ESR or CRP combined with other clues to Rheumatoid arthritis helps make the diagnosis. 

→ Rheumatoid factor (RF). RF is an antibody found (eventually) in about 80 percent of people with Rheumatoid arthritis. 

→ CCP Antibodies IgG/IgA. Antibodies to cyclic citrullinated peptide (CCP) are found in 60 to 70 percent of people with Rheumatoid arthritis. However, they are also found in people without Rheumatoid arthritis. 

Imaging tests:

Rheumatoid arthritis can cause the ends of the bones within a joint to wear down (erosions). An X-ray, ultrasound, or MRI (magnetic resonance imaging) scan can look for erosions. But if they don’t show up on the first tests that could mean Rheumatoid arthritis is in an early stage and hasn’t damaged bone yet. Imaging results can also show how well treatment is working.

Overall diagnosis:

Rheumatoid arthritis is diagnosed by reviewing symptoms, conducting a physical examination, and doing X-rays and lab tests. It’s best to diagnose RA early—within 6 months of the onset of symptoms—so that people with the disease can begin treatment to slow or stop disease progression (for example, damage to joints). Diagnosis and effective treatments, particularly treatment to suppress or control inflammation, can help reduce the damaging effects of RA.

What are the different types of Rheumatoid Arthritis?

Rheumatoid arthritis is classified as either seropositive or seronegative.

People with seropositive Rheumatoid arthritis have ACPAs, also called anti-cyclic citrullinated peptides, found in their blood test. These antibodies attack the synovial joints and produce symptoms of Rheumatoid arthritis.

About 60 to 80 percent of people diagnosed with Rheumatoid arthritis have ACPAs, and for many people, the antibodies precede the symptoms of Rheumatoid arthritis by 5 to 10 years.

People with seronegative RA have the disease without the presence of the antibodies or RF in their blood.

Progression of Rheumatoid Arthritis:

Rheumatoid arthritis is a progressive and chronic disease. Damage to the joint bones occurs very early in the progression of the disease, typically within the first two years. That's why early treatment is so important.

With effective, early treatment, most people with Rheumatoid arthritis can live as they normally would, and many people can achieve remission of symptoms. This doesn't mean that you're cured but rather that your symptoms are alleviated to the point where you can function at your fullest and your joints are not being further damaged by Rheumatoid arthritis. It's also possible to achieve remission and then relapse, or have your symptoms return.

But remission doesn't happen for everyone, and because the pain and other symptoms of Rheumatoid arthritis may change over time, pain management can be an ongoing concern. 

How is Rheumatoid Arthritis treated?

Rheumatoid arthritis can be effectively treated and managed with medication(s) and self-management strategies. Treatment for RA usually includes the use of medications that slow disease and prevent joint deformity, called disease-modifying antirheumatic drugs (DMARDs); biological response modifiers (biologicals) are medications that are an effective second-line treatment.

In addition to medications, people can manage their Rheumatoid arthritis with self-management strategies proven to reduce pain and disability, allowing them to pursue the activities important to them. 

Treatment and Medication Options for Rheumatoid Arthritis:

To treat Rheumatoid arthritis, doctors aim to stop the progression of the disease by reducing symptoms, controlling inflammation, minimizing joint and organ damage, and improving physical function.

Proven treatments include medication and physical therapy. Early, aggressive measures can help control symptoms and complications before the disease significantly worsens, by reducing or altogether stopping inflammation as quickly as possible.

This strategy is essential to preventing disability, and it usually amounts to treatment with anti-inflammatory drugs, and sometimes more than one medication at a time.

Medication Options: 

In recent years, there have been significant advancements in medicines for treating Rheumatoid arthritis, but there is still no cure. Medications known as disease-modifying antirheumatic drugs (DMARDs) are considered the gold standard for Rheumatoid arthritis treatment. DMARDs can change or slow the progression of the disease, helping prevent severe joint damage and other complications.

In general, these drugs work by slowing the inflammation and protecting the joints from further damage, and are generally prescribed shortly after diagnosis. The type of DMARD a doctor prescribes depends on several factors, including disease severity and the balance between the medication's benefits and potential side effects.

Biologics and JAK inhibitors are options alongside traditional DMARDs.

Traditional DMARDs target the entire immune system, while biologics work by targeting specific steps in the inflammatory process, and JAK inhibitors block action in your body to help prevent the inflammation before it starts. Traditional DMARDs are usually taken in pill form, as are JAK inhibitors; biologics are typically injected or delivered via an intravenous infusion.

JAK inhibitors can increase the risk of serious heart-related events such as heart attack or stroke, as well as the risk of cancer, blood clots, and death, especially for past or current smokers and those with existing heart conditions.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are used to treat pain and inflammation. But the latest treatment guidelines issued by the American College of Rheumatology recommend that steroid use be minimized.

Alternative and Complementary therapies for Rheumatoid Arthritis:

Certain lifestyle changes and home remedies may be beneficial — in addition to the conventional treatment of medication, physical therapy, and surgery — if needed.

Some people have found relief from Rheumatoid arthritis symptoms through acupuncture, tai chi, and yoga, though the scientific evidence supporting this isn't particularly conclusive. Complementary or alternative therapies, such as homeopathy, hydrotherapy, or cryotherapy, might also be worth considering to help relieve RA pain and stiffness.

Relaxation techniques, visualization exercises, group counseling, and psychotherapy can help reduce the stress of living with Rheumatoid arthritis. Sleeping well is also an important part of managing symptoms.

You should always check with your medical provider before trying any complementary or alternative therapies.

Many people can manage Rheumatoid arthritis with medication and physical therapy, but joint surgery may be an option if your joint damage is severe and limiting your quality of life.

What are the complications of Rheumatoid arthritis?

Rheumatoid arthritis has many physical and social consequences and can lower quality of life. It can cause pain, disability, and premature death.

→ Premature heart disease. People with Rheumatoid arthritis are also at a higher risk for developing other chronic diseases such as heart disease and diabetes. To prevent people with Rheumatoid arthritis from developing heart disease, treatment of Rheumatoid arthritis also focuses on reducing heart disease risk factors. For example, doctors will advise patients with Rheumatoid arthritis to stop smoking and lose weight.

→ Obesity. People with Rheumatoid arthritis who are obese have an increased risk of developing heart disease risk factors such as high blood pressure and high cholesterol. Being obese also increases risk of developing chronic conditions such as heart disease and diabetes. Finally, people with Rheumatoid arthritis who are obese experience fewer benefits from their medical treatment compared with those with Rheumatoid arthritis who are not obese.

→ Employment. Rheumatoid arthritis can make work difficult. Adults with Rheumatoid arthritis are less likely to be employed than those who do not have Rheumatoid arthritis. As the disease gets worse, many people with Rheumatoid arthritis find they cannot do as much as they used to. Work loss among people with Rheumatoid arthritis is highest among people whose jobs are physically demanding. Work loss is lower among those in jobs with few physical demands, or in jobs where they have influence over the job pace and activities.

It's well established that rheumatic diseases such as Rheumatoid arthritis increase the risks for developing a variety of health conditions.

The most common Rheumatoid arthritis comorbidity (=a disease or medical condition that is simultaneously present) is cardiovascular disease, but the condition is also associated with several specific cardiovascular issues, including heart attack, stroke, congestive heart failure, peripheral vascular disease, and atherosclerosis.

It's important for people with Rheumatoid arthritis to work with their doctors to assess their heart disease risk factors, such as high blood pressure, diabetes, and smoking, and to reduce them.

Rheumatoid arthritis can also lead to inflammation in other areas of the body, including blood vessels, where it's known as rheumatoid vasculitis; the lungs, resulting in rheumatoid lung disease or other conditions; the eyes; and the wrists, causing carpal tunnel syndrome.

Another possible complication is kidney impairment as a result of Rheumatoid arthritis medication. And pregnant women need to be aware that Rheumatoid arthritis is linked to pregnancy complications, such as hypertension (high blood pressure) during late pregnancy, and increased risk of premature delivery.

How to manage Rheumatoid Arthritis?

How can I manage Rheumatoid arthritis and improve my quality of life?

Rheumatoid arthritis affects many aspects of daily living including work, leisure and social activities. Fortunately, there are multiple low-cost strategies that are proven to increase quality of life.

→ Get physically active. Experts recommend that ideally adults be moderately physically active for 150 minutes per week, like walking, swimming, or biking 30 minutes a day for five days a week. You can break these 30 minutes into three separate ten-minute sessions during the day. Regular physical activity can also reduce the risk of developing other chronic diseases such as heart disease, diabetes, and depression. Learn more about physical activity for arthritis.

→ Stop Smoking. Cigarette smoking makes the disease worse and can cause other medical problems. Smoking can also make it more difficult to stay physically active, which is an important part of managing Rheumatoid arthritis. 

→ Maintain a Healthy Weight. Obesity can cause numerous problems for people with Rheumatoid arthritis and so it’s important to maintain a healthy weight.

How to prevent Rheumatoid Arthritis?

→ Stop Smoking. Smoking and exposure to cigarette smoke is a major risk factor for Rheumatoid arthritis. One study found that the risk of developing Rheumatoid arthritis was approximately twice as high for smokers as it is for nonsmokers. Smoking can affect the immune system by increasing oxidative stress on the body, triggering inflammation, and promoting apoptosis (cell death). Quitting smoking and avoiding secondhand smoke might be helpful in preventing the development of Rheumatoid arthritis.

→ Limit Alcohol. Alcohol doesn't have to be completely off the table for people with Rheumatoid arthritis, but it's best to limit your intake. Long-term moderation in alcohol consumption has been linked to lower Rheumatoid arthritis risk in women. When you have Rheumatoid arthritis, the main concern with alcohol is its potential interaction with medications you may be taking for treatment of the condition. Some medications used to treat Rheumatoid arthritis can be damaging to the liver. Alcohol use, which can also hurt the liver, may increase that risk.

→ Minimize Bone Loss. Rheumatoid arthritis is associated with bone loss and osteoporosis. Pain and joint stiffness caused by Rheumatoid arthritis can lead to inactivity, increasing osteoporosis risk. You can help prevent or slow down Rheumatoid arthritis-associated bone loss by:

• Making sure your diet is rich in calcium or vitamin D
• Engaging in weight-bearing exercise
• Avoiding smoking
• Taking supplements for bone health if these nutrients aren't part of your diet

→ Improve Oral Health. Inflammation may contribute to the development of Rheumatoid arthritis. To help prevent inflammation, keep your teeth and gums in good shape, and see your dentist regularly to prevent chronic oral health problems or infections.

→ Maintain a Healthy Weight. A healthy diet can be beneficial when it comes to preventing Rheumatoid arthritis. Obesity has been linked to the condition, and maintaining a healthy weight may reduce your risk of Rheumatoid arthritis. Additionally, a number of vitamins and minerals—like vitamin D and calcium—can help keep Rheumatoid arthritis and osteoporosis from progressing. There is also some evidence that anti-inflammatory diets can help fight RA and other inflammatory diseases. These diets typically rely on elements of vegetarian, gluten-free, and Mediterranean diets. While these diets don't have a significant effect on disease development or progression, eating or avoiding certain foods seems to help some patients with RA when combined with other therapies.

Key aspects of these diets include:

• Vegetarian meals with legumes one to two times each week
• Potatoes
• Whole-grain cereals
• Five or more servings of fruit and vegetables each day
• Probiotics

Superfoods for an anti-inflammatory diet include:

• Tomatoes
• Olive oil
• Spinach
• Kale
• Almonds
• Walnuts
• Strawberries
• Blueberries
• Cherries
• Oranges

Foods best avoided or limited include:

• Meats
• Processed meats
• Red meats
• Margarine
• Lard
• Refined carbohydrates, like white bread
• Fried foods
• Sodas

→ Exercise. All types of exercise—aerobic, weight training, stretching, and yoga—can also be protective against diseases like Rheumatoid arthritis and may help slow progression and relieve symptoms of the disease. Yoga, in particular, can reduce pain, inflammation, and stress, and improve mental health, balance, and strength.

Some of the best examples of exercises for people with RA include:

• Stretching
• Walking
• Yoga and Tai chi
• Aquatic exercise
• Biking
• Strength training

When you have Rheumatoid arthritis, it's important to listen to your body. Be mindful of pain, and don't push yourself to discomfort.

The right equipment, like supportive shoes, can help you stay safe and get the greatest benefit from your efforts.

→ Reduce Exposure to Environmental Pollutants. Environmental pollutants like chemicals used in cleaning and manufacturing have been shown to trigger a host of health problems—especially in people with certain genes. The HLA gene has been tied to the development of RA, and studies have found that pollutants like dioxin and cigarette smoke are associated with disease development in people with this gene. New medications are being investigated to block these actions, but avoidance of harmful chemicals is best when possible.

→ Take Early Action. Rheumatoid arthritis is a chronic, progressive disease that can lead to disabling joint damage. Early symptoms can include morning stiffness that resolves in about an hour. If you think you have Rheumatoid arthritis or are at risk of developing the condition, talk with your healthcare provider. Early and aggressive treatment with medications that help stop inflammation is key to preventing severe joint damage or damage to other organs.

What are laboratory tests for RA?

No laboratory test will definitively confirm a diagnosis of rheumatoid arthritis. However, the information from the following tests contributes to diagnosis and management.

→ Complete blood count (CBC)

→ Comprehensive metabolic panel (CMP)

→ Rheumatoid Factor (RF)

→ Antibodies to citrullinated peptides including anti-CCP

→ Erythrocyte Sedimentation Rate (ESR)

→ C-reactive protein (CRP)

The blood count shows a mild anemia in approximately 25 to 35% of patients with Rheumatoid arthritis. The white cell count is usually normal in patients with rheumatoid arthritis, but can be mildly elevated secondary to inflammation, and can also be very low in a subgroup of patients with Felty’s syndrome. Similarly, the platelet count is usually normal but thrombocytosis occurs in response to inflammation.

Chemistry tests are usually normal in rheumatoid arthritis with the exception of a slight decrease in albumin and increase in total protein reflecting the chronic inflammatory process. Renal and liver function are important to check before beginning treatment and are followed over time with many medications.

A positive rheumatoid factor is present in 70-80% of patients with Rheumatoid arthritis. A positive Anti-CCP is a more specific marker for Rheumatoid arthritis and is found in similar proportions of patients over the course of disease. High levels of Anti-CCP also appear to be linked to a greater severity of the disease.

Measures of inflammation are often, but not always increased in Rheumatoid arthritis. The erythrocyte sedimentation rate (ESR) is usually elevated in patients with Rheumatoid arthritis and in some patients is a helpful adjunct in following the activity of the disease. The C-reactive protein (CRP) is another measure of inflammation that is frequently elevated, and improves with control of disease activity.

Testing for hepatitis B and C and testing for tuberculosis are commonly done as part of an initial evaluation. Baseline X-Rays of the hands, feet, and other affected joints are common at initial evaluation, and sometimes a baseline chest X-Ray is obtained.

Radiographic Findings:

Erosions of bone and destruction of cartilage, occur rapidly and may be seen within the first 2 years of the disease, but continue to develop over time. These anatomic changes result in limitations in range of motion, flexion contractures, and subluxation (incomplete dislocation) of articulating bones. Typical deformities include ulnar deviation of the fingers at the MCP joints, hyperextension or hyperflexion of the MCP and PIP joints (swan neck and boutonniere deformities), flexion contractures of the elbows, and subluxation of the carpal bones and toes (hammer toes and cock up deformities). Radiological findings early in the disease may show nothing other than soft tissue swelling. Thereafter, periarticular osteopenia may develop. With progression of their disease, narrowing of the joint space is caused by loss of cartilage, and juxta-articular erosions appear, generally at the point of attachment of the synovium. In end-stage disease, large cystic erosions of bone may be seen.

More recently the introduction of ultrasound and MRI imaging has improved the sensitivity of detecting joint damage earlier in disease.  Ultrasound may detect synovitis, effusions, and erosions, in addition to power Doppler providing estimates of ongoing inflammation. MRI may show inflammatory synovitis that enhances with Gadolinium and shows early erosions. The role for these modalities in following patients over time in clinical practice is still not well established, but these methods may improve the ability to detect early disease and confirm a diagnosis.