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Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammation of the peripheral joints, leading to pain, stiffness, and joint damage and deformity over time.
It is a systemic condition, which means inflammation may be present throughout the body, causing fatigue, low energy, anemia, and in some cases, involvement of body tissues beyond the joints.
RA is a relatively common disorder and affects 0.24%-1% of the world population.
The incidence of the disease may even be on the rise. In North America, the disease incidence is about 40 per 100,000. (1) Women are affected almost two times more than men.
What are the types of rheumatoid arthritis?
Due to a lack of knowledge about the cause of RA, it is difficult to classify the disease completely.
As different patients exhibit varying progression rates and symptoms, the disease is currently classified into a seropositive or seronegative RA. This basic and primary classification can help determine treatment options.
- Seropositive rheumatoid arthritis: It is determined by the presence of anti-cyclic citrullinated peptides (anti-CCPs) in the blood. Also known as anti-citrullinated protein antibodies (ACPAs), these peptides are produced by the body in response to a molecular change of proteins, called citrullination.
Anti-CCPs are found in around 60%-80% of people having RA. A positive test for anti-CCPs and the presence of RA symptoms are an approximate confirmation of the disease. Initially, this test was performed to check the presence of rheumatoid factor, which is an antibody that attaches to other antibodies.
Various tests can help determine rheumatoid factor levels. However, the anti-CCP test is more specific to RA and is the preferred choice.
- Seronegative rheumatoid arthritis: An absence of anti-CCP antibodies in the blood indicates the possibility of having the seronegative type of RA.
What are the causes of rheumatoid arthritis?
The actual cause of RA is unknown, although there are many theories, including:
- Genetic determinants: Some genes are suggested to be associated with the development of RA.
- Environmental factors: An environmental trigger, such as an infection or a toxin, may trigger the immune system in susceptible persons to develop RA.
- Leaky gut: A leaky gut is often considered a prominent factor. Irritation of the intestinal lining as a result of ingesting certain foods, chemicals, and environmental toxins may result in local inflammation that overwhelms the capability of the gut immune system to contain the irritant. This may lead to systemic immune system activation.
- A poor diet or the overuse of antibiotics: These practices may alter the normal intestinal bacterial population, which leads to “dysbiosis” and further contributes to the leaky gut problem.
- Molecular mimicry: The immune system becomes confused following an infection or environmental exposure and “sees” the body’s own tissue as the foreign invader, thus beginning a continuous attack on the tissue.
What are the signs and symptoms of rheumatoid arthritis?
RA usually presents as symmetrical arthritis, which means both hands, both knees, or both wrists, for example, are affected. This is a characteristic feature of RA.
The most common signs of rheumatoid arthritis include:
- Joint pain and tenderness
- Swelling in the joints
- Redness and warmth in the joint
- Stiffness and restricted range of motion of the joints
- Joint deformity
- Hard bumps (called rheumatoid nodules) around the joints, present below the skin
- Red, puffy hands
- Loss of appetite
Joint stiffness, pain, and swelling are the classic symptoms of rheumatoid arthritis, often associated with fatigue and low energy. Stiffness is particularly common in the morning, upon arising or after a period of physical inactivity.
Unlike the more common osteoarthritis, in which resting the joints generally reduces symptoms, rheumatoid arthritis improves with movement and activity.
How is rheumatoid arthritis diagnosed?
A physician familiar with RA, usually a rheumatologist, is best suited to make a diagnosis of RA. RA is associated with autoantibodies that can be detected with a blood test. Rheumatoid factor is an antibody observed in about 75% of people with RA.
Another blood test often used is the test for the presence of anti-CCP antibodies, which are seen in about 70% of patients with RA. Together, the RF and anti-CCP tests can identify over 80% of patients with RA.
This means that up to 20% or more of patients with RA have negative blood tests for the autoantibodies. We call these cases “seronegative RA,” which means the serum is negative.
For that reason, the diagnosis of RA is not solely based on blood testing. Doctors rely upon a constellation of signs and symptoms that, when taken together, help to establish the diagnosis.
The presence of symmetrical arthritis with swelling, pain, and stiffness in characteristic joints, along with other signs such as X-ray changes and additional blood tests, are all considered to make a determination.
Blood testing may also reveal anemia and an elevated sedimentation rate and C-reactive protein, which are signs of inflammation in the body.
Which joints are most commonly affected by rheumatoid arthritis?
The most commonly affected joints in RA are the hands and wrists, ankles and feet, and knees, although any of the peripheral joints can be involved.
The cervical spine (neck) may also be affected, but the rest of the spine is generally not involved in RA. That is, low back and spine pain is generally not a problem for patients with rheumatoid arthritis.
Although less common, inflammation of the hips and elbows may occur as well. Even the clavicular joints (collar bone) that connect to the sternum (breast bone) or shoulder may exhibit rheumatoid inflammation.
There is also a very specific pattern of hand involvement in RA. The large knuckles (the metacarpophalangeal, or MCP, joints) and the first finger joints (proximal interphalangeal, or PIP, joints) are commonly affected with stiffness, pain, and swelling.
The smallest finger joints, the distal interphalangeal (DIP) joints, are not involved, unlike in osteoarthritis of the hands, which typically spares the MCP joints and impacts the PIP and DIP joints.
RA may involve multiple joints or just a few. Sometimes, a person can have severe disease and damage in one or two joints with no involvement elsewhere. Others have mild or moderate severity but the involvement of many joints.
What are the different stages of rheumatoid arthritis?
Rheumatoid arthritis has four stages, which indicate disease severity.
- Stage 1, mild or early-stage RA: In this stage, there is evidence of joint swelling and stiffness but no deformities, and the X-rays indicate no underlying bone damage.
- Stage 2, moderate disease progression: In this stage, there may be subtle radiographic signs of joint injuries, such as cartilage loss or early bone changes. The joint swelling has advanced and may be impacting the range of motion of the joint, but deformity is not apparent.Some adjacent muscle atrophy may have developed. Rheumatoid nodules and soft tissue swelling may develop. These are indications of “extra-articular” involvement, which means there is tissue inflammation beyond the joints.
- Stage 3, advanced disease: There is joint swelling, loss of range of motion, and deformity. X-Rays reveal substantial joint damage with bone erosion and extensive loss of cartilage.There is significant muscular atrophy around the affected joints. Extra-articular disease involvement is more commonly seen in stage 3 RA.
- Stage 4, end-stage or terminal disease: In this stage, advanced damage has developed with joint deformities and loss of function. There may be bony “ankylosis,” which means the joints have fused together and become rigid.In this situation, there is no longer inflammation ongoing in the joint, since all the target tissue has been lost. Still, pain and stiffness persist.
Can rheumatoid arthritis affect other body parts besides joints?
Yes, indeed! There are many “extra-articular” manifestations of RA. As mentioned, rheumatoid nodules, which are soft tissue swelling beneath the skin, may appear almost anywhere, though often found at the elbows and over the knuckles or hands.
Tenosynovitis, which is swelling of the tendons, may usually occur in tendons adjacent to affected joints.
The eyes may be affected, manifested as scleritis and episcleritis, which causes red and painful eyes, photosensitivity (light sensitivity), and visual disturbances.
The rheumatoid lung is a relatively common extra-articular disease manifestation in which nodules and lung opacities may be seen on X-ray.
A severe form of RA, fortunately quite rare, is “rheumatoid vasculitis,” in which inflammation progresses to involve the blood vessels, causing interrupted blood flow. This often presents as ulcers on the legs and can damage the peripheral nerves, leading to sensory changes and weakness.
Some patients with RA develop Sjogren’s syndrome, in which autoimmune inflammation affects the secretory glands of the body, leading to dryness. The eyes and mouth are typically affected, as tears, and saliva production are impaired.
Sjogren’s syndrome may also cause respiratory, nerve, skin, and gastrointestinal problems and can be a struggle for the RA patient with this extra-articular disease complication.
What factors may increase your risk of rheumatoid arthritis?
Several factors can predispose you to develop RA, including:
- Genes: Heredity may play a role in RA development. However, the likeliness is low as genes do not contribute significantly to the development of the condition.
- Environment: Toxic substances, such as air pollution, chemicals, smoke, and insecticides, can negatively affect the body, often contributing to the joint pain in patients with RA.
- Smoking: Smoking is suggested to increase the risk of developing RA.
- Hormones: More women are seen to be affected by RA than men. This could be indicative of a link between female hormones and RA.
- Lifestyle: Researchers suggest that poor lifestyle habits such as smoking, obesity, and poor health could contribute to joint pain and stiffness in patients with RA.This consideration is based on the negative impact of a poor lifestyle on a person’s immune system, thereby enabling diseases such as RA to develop more easily.
Based on the severity and type of exposure, all these factors are likely to contribute to the development of autoimmune diseases such as rheumatoid arthritis.
Are rheumatoid arthritis and fibromyalgia different conditions?
Yes, they are very different. RA is an autoimmune condition primarily affecting joints, in which the synovium (joint capsular membrane) becomes inflamed, causing stiffness and pain primarily in the affected joints.
Fibromyalgia (FMS), on the other hand, is not a joint disease. Although patients with FMS experience significant musculoskeletal pain, the pain is generally widespread and diffuse and often affects the muscles, especially of the extremities and back.
FMS is not an arthritis condition, nor is it considered to be an inflammatory or autoimmune disorder.
Rather, FMS is most likely a central nervous system condition, in which abnormal sensory processing in the brain leads to hyperalgesia (exaggerated pain sensitivity) and allodynia (experience of pain from stimuli that ordinarily do not induce pain).
Is rheumatoid arthritis hereditary?
Yes. There is clearly a familial association. A person with a first-degree relative with RA has about three times the risk of developing the condition, and those with a second-degree relative have double the risk. (2)
Over 100 susceptibility genes are associated with RA risk, most notably the HLA-DRB1 region of the genome, which is involved in immune response regulation (major histocompatibility gene complex).
Certain inherited genes associated with this region are seen in over 50% of Caucasian patients with RA, conferring a risk of 5-10 times the average RA risk. (3)
Can rheumatoid arthritis lead to multiple sclerosis?
Possibly. An association between RA and multiple sclerosis is not clear but has been reported. The data are mixed, but there may be a higher incidence of RA among patients with multiple sclerosis. (4)
Should any dietary restrictions be implemented when you have rheumatoid arthritis?
Yes. This remains a controversial area, as there is no single dietary approach that has been shown to be effective for all RA sufferers. Consequently, there are no standard dietary recommendations advised by the professional rheumatology associations.
And for years, it has been known that patients with RA who fast and are fed intravenously an elemental diet experience improvement.
So, diet and nutrition are very important, but each person with RA has to explore different dietary strategies to determine which is best for him/her.
The foods you eat play an important role in your health. Some foods can cause inflammation and contribute to the development and persistence of autoimmune and chronic diseases, such as RA.
Because people all differ genetically, no single dietary approach is optimal for all people. Unfortunately, despite some claims to the contrary, there is no blood or other test available that can accurately identify foods that are responsible for causing inflammation in any particular person.
So, determining which foods are bad for you can be very challenging. However, in most cases, people with RA should dispense with the “Standard American Diet,” which is rich in added sugars, sodium, trans-fats, starches, and processed foods of all kinds.
Instead, a modified anti-inflammatory diet is recommended. This is a diet rich in whole foods and mostly plant-based with lean protein sources. This means avoiding as completely as possible all added sugars and artificial sweeteners as well as processed foods.
Foods in a box or most frozen meals should be minimized. Learn to read labels, if there are additives that confuse you or items listed that you cannot pronounce, avoid that product!
Whole foods are essential. Whenever possible, choose organic foods, especially when it comes to “the dirty dozen,” or those foods with the most herbicides and pesticides.
What about carbs?
Reduce carbs, which include bread, bagels, muffins, crackers, pasta, and cookies (anything made with flour).
Whole grains are fine with many patients with RA, but some patients are gluten-sensitive and should avoid even “healthy” grains.
Be careful with “whole-wheat” products, which are often only partly whole and largely processed with bleached flour. Processed grains tend to be inflammatory.
It is not clear that the culprit in grains is gluten. Other nutrient factors have been proposed, but whatever the specific cause, avoiding refined grains is important.
What about fiber? Isn’t that an important feature of grains?
While fiber is very important for your health and supports a normal microbiome balance, promotes bowel regularity, and reduces colon cancer risk, you can get fiber from fruits and vegetables.
Green vegetables and cruciferous veggies, in particular, not only are great sources of fiber but also provide numerous phytonutrients, antioxidants, vitamins, and polyphenols.
What about dairy products?
Once again, foods such as milk, cheese, and yogurt may be fine for some RA sufferers, but many find these products can aggravate their arthritis.
Dairy sensitivity differs from lactose intolerance. It is the milk proteins that are inflammatory in many people.
Elimination of dairy products from the diet often results in a reduction of joint pains and achiness, improved feelings of energy, and less allergy and mucus production.
The following food groups are also frequently cited as possessing pro-inflammatory factors in some people:
- Corn and all corn products (corn products are commonly used in processed foods of all kinds: read labels!)
- Legumes (beans, lentils, chickpeas, and peanuts)
So, you may consider a trial of eliminating these if you are still struggling despite the avoidance of carbs and dairy.
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- Foods That Promote and Reduce Inflammation
What about nightshade vegetables and tree nuts?
Many experts warn against the inclusion of these foods in patients with arthritis, but these are not commonly inflammatory.
For most, these foods (tomatoes, peppers, eggplant, almonds, cashews, walnuts) are very healthy and are packed with proteins, phytonutrients, antioxidants, polyphenols, and “good fats.”
Still, some RA sufferers do struggle with them, so it is worth considering eliminating these for a trial to see how arthritis responds.
Is rheumatoid arthritis curable?
Not presently. (9) But many medications are available that can control the disease, reduce the pain and joint swelling, and protect against joint damage over time.
In fact, over 90% of patients with RA who receive proper treatment can live active lifestyles, remain employed, and enjoy normal family life. (10)
The medical treatment of a patient with RA involves considering the goals of therapy.
Some medications, such as NSAIDs and Tylenol, are helpful in treating symptoms of pain, swelling, and stiffness, but these do not impact the disease course.
Antirheumatic agents, on the other hand, are medications that are intended to modify the disease course, reduce the risk of joint damage over time, and suppress the RA activity in the body.
These medications do, in effect, relieve symptoms over time by treating the underlying disease process. These “antirheumatic” drugs, also called disease-modifying antirheumatic drugs (DMARDs) are the mainstays of RA treatment.
Examples of these medications are methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine.
When DMARDs are insufficiently effective in a patient with RA, the next step is the addition of biologic agents, such as infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), and abatacept (Orencia).
Biologic drugs are extremely effective and have changed the lives of thousands of patients with RA since their development.
At times, corticosteroids, such as prednisone, may also be used, but generally in low doses or for a limited time, since these medications, while extremely effective, present significant side effects with continued use.
A treatment program for the patient with RA, customized by the treating rheumatologist, can be extremely effective. However, it is complex and requires careful monitoring to avoid side effects and ensure proper use and effectiveness.
Are physical therapies helpful? If yes, then what exercises are helpful?
Yes. Maintaining range of motion in the joints is very important, as well as strength and flexibility of the muscles and tendons around the joint structures.
Can surgery be beneficial to a person suffering from rheumatoid arthritis?
If a joint becomes severely damaged, usually seen in stages 3 and 4 RA, joint replacements may be required. Knee and hip surgical replacements are generally quite successful, as are shoulder joint replacements.
But for smaller joints, such as those of the hands and feet, wrists, and elbows, joint replacement surgery is not available.
Some orthopedists perform ankle replacement surgery, but this procedure has mixed success. There are no surgical interventions that treat RA, per se, only end-stage joint damage.
What lifestyle changes should be followed by a person who has rheumatoid arthritis?
Low-impact exercises, such as walking, yoga, and swimming, done regularly can be very helpful in maintaining joint function and neuromuscular tone.
Patients with RA become easily fatigued and require rest periods. But they should also avoid prolonged periods of inactivity, which leads to the “gel phenomenon,” in which the joints become stiffer and set like gelatin due to a lack of movement.
It is also very important to get adequate sleep and manage stress, both of which can impact disease activity. Additionally, losing excess weight, along with consuming a healthy diet, can help improve the disease.
Establishing a relationship with a rheumatologist to help with disease management is very important.
What are the possible complications of rheumatoid arthritis?
Patients with RA also have about twice the risk of lymphoproliferative diseases, such as leukemias and lymphoma.
Some of the medications used for RA treatment may result in adverse effects and can increase the risk of infection or kidney problems, thus requiring close monitoring.
In general, patients with RA have frequent “comorbidities,” that is, other chronic disorders that complicate their overall health. (12)
When to see a doctor?
It is recommended to schedule a visit to your doctor if you experience swelling and soreness in your joints for weeks. Additionally, if you feel stiffness in the morning, seek medical help, as this could be indicative of RA.
It is essential to get a timely diagnosis and treatment as RA is an immune system disorder that may cause complications if not managed well.
Expert Answers (Q&A)
Answered by Dr. Rajat Bhatt, MD (Rheumatologist)
What is the difference between osteoarthritis and rheumatoid arthritis?
Osteoarthritis is degenerative arthritis that occurs with age or secondary to injury. Rheumatoid arthritis is inflammatory arthritis in which the body starts attacking its own joints and leads to inflammation and deformities.
Does stress lead to flare-ups of rheumatoid arthritis?
Yes, physical or psychological stress can lead to flare-ups of rheumatoid arthritis.
What are the consequences of leaving rheumatoid arthritis untreated?
Joint deformities can develop, and the condition can have adverse effects on workability. It can also lead to intractable pain.
Is coffee bad for rheumatoid arthritis?
Would exercises be of any help for someone suffering from rheumatoid arthritis?
It depends on the joints involved. Hand exercises often help. Squeezing a ball and stretching the back and hips also might help.
What dietary changes should be made when suffering from rheumatoid arthritis?
Avoid an inflammatory diet, red meat especially. Some studies show avoiding sugar might help as well. (13)
What important points should be kept in mind when dealing with rheumatoid arthritis?
Have a mind-body balance. Exercise control over your flare-ups and have a self-management plan. Discuss these goals with your doctor.
Also, try natural therapies such as turmeric. Eat healthy and maintain a normal weight. Quit smoking as smoking is a risk factor for worsening of rheumatoid arthritis.
About Dr. Rajat Bhatt, MD: Dr. Bhatt is board-certified in rheumatology and internal medicine. He completed his residency at Mount Sinai Hospital in New York. Subsequently, he did a fellowship in echocardiography at Methodist DeBakey Heart Center in Houston and also pursued a second fellowship in rheumatology at LSU Health Shreveport.
Dr. Bhatt provides comprehensive care to patients by incorporating medical and alternative approaches. He is also interested in health information technology and artificial intelligence for improving diagnosis and patient care. He was the ACR international fellow of the year and spent some time at prestigious institutes in India, learning and contributing to rheumatology.