Rheumatoid Arthritis

What is Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is a long-term illness, stemming from the body’s immune system attacking its own tissues, primarily the lining of joints. This not only causes joint pain and swelling but may also affect other parts of the body. The disease often results from a combination of genetic and environmental factors, including smoking. RA usually starts in small joints like hands and feet, often affecting the same joints on both sides of the body, and can spread to larger joints if untreated.

With time, the ongoing inflammation can damage the joint, leading to loss of cartilage (a cushion-like material inside the joint) and bone erosion (loss). If someone has RA symptoms for less than six months, it is considered early RA, but if the symptoms have lasted for more than six months, it is referred to as established RA.

It’s important to note that RA, if untreated, can worsen over time, causing health complications and even leading to a decreased lifespan.

Diagnosing RA can be difficult, especially in the early stages, because there isn’t a single conclusive test for it. A thorough clinical examination is necessary to confirm the diagnosis and to prevent further damage to the joints. Treatment for RA involves a combination of medications and lifestyle modifications. Presently, early treatment with drugs intended to modify the course of the disease is the standard approach. Despite treatment, many individuals with RA may still develop disabilities and face significant health challenges over time. Hence, along with medications, other forms of treatment such as physical therapy, counseling, and patient education are needed to improve patient outcomes.

What Causes Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is believed to be caused by a combination of genetic predispositions and environmental triggers. Genetics seem to play a significant role, with studies suggesting that your chance of developing RA is 40% to 65% if you’re seropositive for the disease (meaning, certain anti-RA antibodies are found in your blood) and 20% if you’re seronegative. Certain genes, like HLA-DRB1*04, HLA-DRB1*01, and HLA-DRB1*10, are associated with a higher risk of developing RA. These genes have a small, consistent section—called a “shared epitope”—that’s linked to the disease.

But there are also several other genes tied to RA risk, including PAD14, PTPN22, CTLA4, IL-2RA, STAT4, TRAF1, CCR6, and IRF5. Some variations of these genes (known as polymorphisms) are found more commonly in people with severe RA, and others occur more often in certain ethnic groups.

Epigenetics, on the other hand, are hereditary changes that don’t change your DNA but can still affect how your body works. These alterations may occur in your genes’ rafts (chromatin) or in your DNA itself. Instance, in people with RA, a certain gene (PTPN11), when altered in this way can encourage more aggressive behaviors.

Environmentally, cigarette smoking is a major risk factor for RA. Smokers who have the shared epitope are especially at risk.
Other triggers related mainly with seropositive RA include exposure to asbestos, textile dust, silica, or the bacteria P. gingivalis. All of these can incite an autoimmune inflammatory reaction in the joints, causing RA.

Researchers are also exploring the gut microbiome’s possible role in RA. They’ve found that RA patients tend to have less diverse gut bacteria, including higher numbers of certain bacteria like Actinobacteria, Collinsella, Eggerthalla, and Faecalibacterium, which could be disturbing the gut’s permeability and worsening RA.

Essentially, both, a person’s genetic predisposition and their exposure to certain environmental factors could contribute to the development of RA. However, as with many complicated diseases, the picture is not fully clear yet and further research is needed to better understand these relationships.

Risk Factors and Frequency for Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is a condition that affects around 0.24% of people globally. It is more common in Western and Northern Europe, North America, Australia, and regions with people of European background. RA is less common in Central and South America, and its lowest presence can be found in East Asia and Africa. In the United States and other western countries in northern Europe, almost 40 out of 100,000 people develop RA every year. Interestingly, women are more likely to get RA than men, with almost 3.6% of women compared to 1.7% of men expected to develop RA in their lifetime. The chance of getting RA rises with age, and its highest occurrence is seen in people between 65 to 80 years old.

A healthy and balanced diet can reduce your risk of getting RA. Unhealthy habits like smoking and a diet low in fiber, but high in calories, increase its risk. Consuming omega-3 fatty acids, found in fatty fish like salmon, seems to lower the risk too. People with obesity also have a higher likelihood of developing this disease.

There seems to be a genetic predisposition to RA as well. If you have a close relative with RA, your chances of getting RA are higher. The strongest genetic link is from a specific region in our DNA, referred to as the HLA-DRB1 region.

It has been suggested that chronic gum disease might increase a person’s risk for RA. However, the studies don’t provide a clear link yet. But, exposure to environmental pollutants that cause injuries to the lining of several body cavities, such as the mouth, might play a role in RA development as well.

• RA is a global condition with a prevalence of 0.24%
• It’s more common in people of European descent.
• Nearly 40 per 100,000 people are diagnosed with RA each year in the United States and northern Europe.
• RA is more common in women and typically occurs between the ages of 65 and 80.
• Smoking and a high calorie, low fiber diet can increase the risk of RA.
• Obesity can also increase the risk of getting RA.
• There’s a genetic component to RA, especially if you have a close relative with the condition.
• Chronic gum disease might play a role in getting RA, but the research is still unclear.

Here is a breakdown of RA prevalence around the world:

• North America:
  • From 10 studies, the pooled prevalence is 0.70% (0.57-0.86)
• Europe:
  • From 26 studies, the pooled prevalence is 0.54% (0.50-0.59)
• Africa:
  • From 3 studies, the pooled prevalence is 0.52% (0.00-1.74)
• Asia:
  • From 26 studies, the pooled prevalence is 0.30% (0.23-0.37)
• South America:
  • From 2 studies, the pooled prevalence is 0.30% (0.09-0.62)
• Global:
  • From 67 studies, the pooled prevalence is 0.46% (0.39-0.54)

Signs and Symptoms of Rheumatoid Arthritis

Rheumatoid arthritis (RA) often begins as mild joint pain and swelling, which typically increase gradually over weeks or months. Commonly, the smaller joints of the hands and feet are affected first, with the larger joints following. Morning stiffness is another classic symptom. Certain cases might see symptoms coming and going, a condition known as palindromic rheumatism. It’s important to note that not everyone with palindromic rheumatism goes on to develop RA.

RA usually affects the small joints, especially in the hands. However, it can also affect the cervical spine (upper part of the spine). The lower part of the spine is usually not affected. In addition to multiple small joints, some patients might have an isolated joint or even lung involvement. If not treated promptly with medication, RA can cause joint damage, deformities, disability, and even increase the risk of death.

On physical examination, you’ll notice that the affected joint feels painful when pressure is applied, or during movement, even without apparent swelling. Thicker joint lining can give a “boggy” feeling when touched. Traditional redness and warmth might be absent, and symptoms of carpal tunnel syndrome could be seen if the wrists are affected. When multiple joints are affected, one might notice reduced gripping strength. In advanced stages, multiple physical changes like finger and toe deformations can be observed, along with reduced range of motion in the shoulders, elbows, and knees.

Rheumatoid nodules are the most common outward sign of RA, often found on pressure points like the elbow, but they can also appear on the joints of the hands and feet, the kneecap, and the Achilles tendons.

Interstitial lung disease, which affects a small percentage of RA patients, is another complication associated with RA. This might even occur in some patients before joint inflammation sets in.

Eye conditions such as dry eyes due to secondary Sjogren syndrome, and inflammation of the outer layer of the eye (episcleritis and scleritis) could also occur. Felty syndrome, comprised of prolonged RA, low white blood cell count, and an enlarged spleen, is rare these days. These patients might have long-lasting non-healing wounds and a higher risk of bacterial infection. A lower percentage of RA patients might also show symptoms of vasculitis, which is inflammation of blood vessels.

Testing for Rheumatoid Arthritis

If you’re suspected of having rheumatoid arthritis (RA), your doctor will likely run a series of tests. Often, these tests will find signs of long-term illness and an increase in platelets, which are blood cells that help with clotting. In some rare cases, there may be a decrease in a type of white blood cell called neutrophils, a condition known as Felty syndrome.

In 80-90% of patients with RA, a protein called Rheumatoid Factor (RF) is found, which indicates the immune system is attacking healthy body tissue. Similarly, another protein called Anti-Citrullinated Protein Antibody (ACPA) is found in about 70-80% of patients. If you have either of these proteins, or both, your RA is referred to as ‘seropositive’. However, about 10% of patients won’t have either protein present; these cases are called ‘seronegative’ RA.

Having RF can’t alone confirm RA as it could also indicate other diseases like lupus, Sjogren syndrome, and scleroderma, or even show up in healthy people. But the chances of an accurate RA diagnosis go up significantly if both RF and ACPA are present.

When someone with inflammation in their joints comes to see a doctor, tests for RF and ACPA should generally come back positive. These proteins can even show up months or years before the first symptoms of RA appear. Healthy people who have relatives with RA and test positive for these proteins are more likely to develop the disease themselves.

Other tests for inflammation like the Erythrocyte Sedimentation Rate (ESR) test and the C-reactive protein (CRP) test, can be used in patients with active RA to help assess the severity and monitor progress of the disease.

Examining the fluid in the joints, or ‘synovial fluid’, can sometimes reveal a high white blood cell count, which could signal very active disease or infection. Similarly, low levels of certain proteins (C3 and C4) could indicate RA, even if levels in the blood are normal.

Advanced RA can cause physical changes to the joints, visible on an X-ray as thinning around the joints, a reduction in joint space, and erosion of the bones. MRI and ultrasound can often spot these changes before they show up on an X-ray. Specifically, MRI can show synovial thickening and signs of bone marrow edema (abnormal fluid in the bone marrow), which are good indicators for the future presence of bone erosion.

Because RA looks different in every patient and no definitive test can confirm it, doctors usually diagnose the disease based on a combination of lab results, symptoms, and imaging studies. Traditionally, you’d need to have at least four specific signs of the disease for at least six weeks to be classified as having RA. But now, with newer blood markers, the diagnosis is made based on a point system that considers factors such as the number and size of affected joints, results of blood tests for RF and ACPA, other signs of inflammation, and how long you’ve had symptoms.

If your total score is 6 or more, it’s classified as RA. It’s important to note that this point system is mainly used for research studies, and your doctors may also use imaging studies and physical exams to make a diagnosis. Additionally, these criteria may not apply to everyone, especially if the joint swelling can be better explained by another disease. In this case, specific tests will be needed to rule out those other diseases.

Treatment Options for Rheumatoid Arthritis

The primary goal in treating patients with rheumatoid arthritis (RA), a chronic inflammatory disorder affecting the joints, is to catch it early and start treatment as soon as possible to prevent irreversible harm to the joints. According to the International Task Force Guidelines, the focus of treatment is to make symptoms disappear over the long term and improve the patient’s quality of life. If the signs and symptoms cannot be fully removed, keeping the disease at a low activity level is considered an acceptable alternative. Regular check-ups are recommended, with the frequency varying depending on the severity of the disease.

Different tools have been developed to help doctors assess how active the RA is in a patient. A recommendation from the American College of Rheumatology suggests a combination of the DAS28, CDAI, and RAPID3 tools, which combine input from both the patient and provider, along with lab tests.

Various drugs such as disease-modifying antirheumatic drugs (DMARDs) – including methotrexate, hydroxychloroquine, and leflunomide – are normally used in treating RA. Other types of DMARDs can also be used, such as anti-TNF-alpha inhibitors and Janus kinases (JAK) inhibitors. These medications might need to be paused in the case of a serious active infection and can be resumed once the infection has been treated.

It’s crucial to remember that all patients starting treatment for RA need to be tested for hepatitis B and C and tuberculosis. Certain types of these drugs should be avoided in patients with specific conditions, like liver disease or latent tuberculosis.

Non-steroidal Anti-inflammatory Drugs (NSAIDs) are typically used to relieve symptoms like joint inflammation and pain. There’s a wide range of these drugs, and the specific choice will depend on the individual patient’s needs and the doctor’s experience with the drug. However, it’s worth noting that these drugs can potentially have serious side effects, like heart complications.

Corticosteroids are often used in patients with RA; they are prescribed when the disease is very active or when a flare-up occurs. However, their long-term use can bring about undesired side-effects, like weight gain, increased risk of infection, and bone thinning (osteoporosis).

TNF inhibitors, another category of drugs, are recommended for use when a nonbiologic DMARD treatment was not successful. Their main concern is increasing the likelihood of opportunistic infections and reactivating latent tuberculosis.

Several specific drugs and combinations thereof are recommended depending on the patient’s condition and how they have responded to previous treatments. Regular assessments of the disease’s activity will guide the adjustments made to the treatment plan.

In terms of safety, all biologic and targeted synthetic DMARDs can increase the risk of infections. Doctors advise pausing therapy during an active infection or for a surgery, and avoid live vaccines while being treated with these drugs. Other potential risks related to these drugs may include shingles; low white blood cell count; elevated levels of liver enzymes and cholesterol; and in rare cases, abnormal clotting and heart failure.

The key takeaway is that each patient’s treatment plan will be unique and tailored based on their specific situation, how they respond to treatment, and any potential side effects. It’s important to have regular check-ups and maintain open communication with your doctor to find the best treatment for your condition.

What else can Rheumatoid Arthritis be?

When dealing with joint pain or problems, doctors consider a range of conditions that might be causing your symptoms:

• Osteoarthritis – wear and tear of the joints over time
• Psoriatic arthritis – a type of arthritis that affects people with psoriasis, a skin disorder
• Systemic lupus erythematosus – a complex disease that can affect various parts of the body, including the joints
• Sjogren syndrome – a disorder that mostly results in dry eyes and mouth, but can also cause joint pain
• Polymyalgia rheumatica – an inflammatory disorder causing musculoskeletal pain and stiffness
• Chronic gouty arthritis – accumulation of uric acid crystals causing intense joint pain primarily in the big toe
• Calcium pyrophosphate deposition disease – arthritis caused by deposits of calcium pyrophosphate crystals within the joint

What to expect with Rheumatoid Arthritis

Rheumatoid arthritis is a disease that worsens over time, causing severe discomfort and an increased risk of death. It doesn’t currently have a cure. Everyone with this condition will experience recurring flare-ups. Furthermore, without treatment, they often suffer from disability and a higher risk of death.

Studies have shown treating early—that is, within six months of noticing symptoms—can improve the patient’s ability to function and reduce signs of the disease, such as swelling and tenderness in the joints. Intriguingly, whether treatment began early or late (beyond six months after symptoms started), the risk of death remained the same. But in both cases, it was considerably lower than for those who received no treatment at all. Sadly, approximately 40% of people with rheumatoid arthritis battle with daily activities and are unable to work within a decade of being diagnosed.

Rheumatoid arthritis also increases the chances of developing other long-term medical conditions or complications that can significantly affect their health outcomes. One of the most significant relationships is between rheumatoid arthritis and atherosclerotic cardiovascular disease, which speeds up the degeneration of the coronary artery. As a result, people with rheumatoid arthritis are more likely to face heart disease, lung diseases, and cancer, which ultimately boost the risk of premature death.

Possible Complications When Diagnosed with Rheumatoid Arthritis

Rheumatoid arthritis (RA) can have many complications with effects on multiple organs. These complications can worsen the health effects of these patients. It is therefore crucial that doctors keep a close eye on their patients for any signs of such issues arising and make changes to the treatment plan promptly. An example is the serious opportunistic infections that some RA patients get. In such cases, doctors may have to stop DMARD therapy until the infections are treated. These infections are believed to be due to an impaired immune system caused by RA and DMARD therapy.

Additional issues linked to systemic inflammation that isn’t controlled include:

• Chronic inflammation of the joints that can lead to damage that can be seen on radiographic images, progressive bending out of shape, and disability
• Anemia as a result of chronic sickness and Felty syndrome are also complications generally seen in patients with RA
• Rheumatoid vasculitis, inflammatory eye disease, and Felty’s syndrome – these are not usually common but can have severe consequences

Lung diseases like pleuritis, bronchiolitis, and interstitial lung disease are also connected to RA. Treatments using methotrexate and anti-TNF agents can sometimes lead to lung injuries. Some patients with RA may even develop interstitial lung disease (ILD). This affects about 5 to 16% of RA patients and generally results in higher mortality rates. Some patients may first show signs of ILD before they develop joint inflammation.

People with RA stand a higher risk of getting coronary artery disease (CAD), and the disease appears to speed up the advancement of CAD in such people. A major cause of death and sickness in people with RA is accelerated atherosclerosis, which can lead to CAD and peripheral vascular disease. RA treatment with DMARDs like hydroxychloroquine, methotrexate, and TNF antagonists can result in improved glucose control and a reduced risk of cardiovascular events.

RA patients also have a higher risk of getting lymphoma, with non-Hodgkin lymphoma being more common among these individuals.

Other complications of rheumatoid arthritis include:

• Earlier death
• Severe infections
• Osteopenia and osteoporosis
• The risk of fractures increases 60% to 100% in RA patients, compared to people without RA
• A higher risk of venous thromboembolic disease
• Depression is also a significant complication of RA, with 17% to 39% of patients developing it

Preventing Rheumatoid Arthritis

Rheumatoid arthritis (RA), a type of arthritis causing painful swelling in the joints, is often linked to genetics, which means you can’t completely prevent it. However, you can cut down your risk by managing certain lifestyle factors. These include avoiding smoking and eating a balanced diet. If you are at risk of developing RA, you should try to eat a healthy, balanced diet, exercise regularly, and keep your body weight in check. This life changes can help reduce your risk of this painful condition.