Arthritis: What is Arthritis?
The word arthritis is derived from the Greek word arthron (joint) and the suffix -itis (inflammation). For people who have arthritis, the word variously signifies pain, swelling, redness, and heat that may be caused by tissue injury or disease in the joint.
Osteoarthritis is the most common type of arthritis. It is also called “degenerative joint disease” because it results from the deterioration of the cartilage in the joints. The second most common type of arthritis, rheumatoid arthritis, is an inflammatory disease that affects the lining of multiple joints, especially in the hands and feet. (The term rheumatism refers broadly to connective tissue disorders that cause pain and stiffness.) Although it affects far fewer people than osteoarthritis, rheumatoid arthritis can be much more debilitating. The other rheumatic diseases discussed in this report — gout, pseudogout, ankylosing spondylitis, reactive arthritis, psoriatic arthritis, enteropathic arthritis, and infectious arthritis — are also characterized by joint inflammation.
The musculoskeletal system
All types of arthritis affect the musculoskeletal system in some way, although the joints involved and the means of damage may vary.
The arrangement of bones and muscles in the body is a marvel of engineering. A model of a skeleton may look rickety and frail, but bones have a compression strength equaling that of cast iron or oak. Although incredibly light — the average adult skeleton weighs only 20 pounds or so — bones are capable of bearing tremendous weight. Their strength is necessary to withstand the forces of movement. When you walk at a leisurely pace, each foot strikes the ground with a force about three times your weight. At a brisk walk or run, the pressure increases to five to six times your weight. In other words, a 150-pound person’s lower extremities are repeatedly subjected to 450 to 900 pounds of force during normal daily activity.
The arrangement of muscles helps hold the skeleton together and, at the same time, provides a means of moving individual bones. Tendons and ligaments, the structures that bind bone and muscle, are made of connective tissue. The main proteins that make up connective tissue are collagens and elastins, which imbue it with tensile strength and elasticity.
Types of joints
There are three basic types of joints (see Figure 1). Fixed joints, or sutures, are thin bands of fibrous tissue that connect the platelike bones of the skull, allowing the skull to expand and accommodate the growing brain. When brain growth is complete, these fibrous joints disappear as the skull bones fuse together.
Cartilaginous joints contain tough cartilage plates. In the pelvis, these joints permit slight movement of the pubic bones and the sacroiliac joint, where the sacrum (part of the spinal column) and pelvis meet. The disks between the vertebral bones in the spine are thicker and accommodate greater mobility.
The most mobile joints are the synovial joints of the shoulders, elbows, wrists, fingers, hips, knees, ankles, and toes. Surrounding each of these joints is a loose fibrous capsule lined with a thin membrane called the synovium. Synovial joints are designed for a variety of movements that make possible all manner of activity, from playing tennis to playing piano. Some — for example, the outermost joints of the fingers — are limited to flexion and extension (bending and straightening) within a single plane. Others, such as the shoulder, wrist, and hip, are capable of complex movements in multiple planes.
Figure 1: Types of joints
There are three basic types of joints. Fixed joints connect the platelike bones of the skull. Cartilaginous joints, such as those in the spine, contain tough cartilage-like plates that bend. The most mobile are synovial joints, which are surrounded by a loose fibrous capsule lined with a thin membrane called the synovium.
Synovial joints, like machines with moving parts, are vulnerable to friction. If a machine’s moving parts come in contact with one another, friction will scratch the surfaces and cause pitting, distortion, and eventually breakage. Two strategies can prevent such friction: applying a lubricant, or inserting a cushion, such as a rubber gasket. Human joints are protected in both ways (see Figure 2).
Synovial fluid is a viscous, yellowish, translucent liquid. Produced by the synovium, it oils the joint and minimizes friction. It also helps protect joints by forming a sticky seal that enables abutting bones to slide freely against each other but resist pulling apart. Places where tendons and muscles cross a bone or another muscle are also subject to friction. These sites are protected by bursae, sacs that not only contain lubricating fluid but also act as cushions.
Articular cartilage, a tough and somewhat elastic tissue that covers the ends of bones, provides joint cushioning. Because it’s about 75% water, cartilage compresses under pressure (as occurs with jumping or even walking) and resumes its original thickness when the force is released, much like a very tough sponge. Because the articular cartilage can mold to its surroundings, the opposing surfaces of a joint are perfectly matched.
Several things maintain stability through a joint’s range of motion so that the joint can function normally. One is the contour and fit of the joint surfaces themselves. The hip, for example, is a ball-and-socket arrangement. With each stride, the head of the femur (thighbone) pushes deep into the cup-shaped cavity of the pelvis, providing maximum stability during walking. Most other joints are more like hinges.
Ligaments, which are tough, slightly elastic, fibrous bands that bind the bones together, also help with alignment. For example, ligaments on the sides of the finger joints prevent side-to-side bending, while ligaments stretching across the palm keep the fingers from bending too far backward.
Muscles and tendons, the fibrous cords that attach muscle to bone, stabilize joints as well as move them. The best example of how this works is in the shoulder, which has such a wide range of motion that ligaments would impede it. While the large, visible shoulder muscles supply the power to move the shoulder, the small rotator cuff muscles and tendons keep the head of the humerus (upper arm bone) from slipping out of the glenoid fossa, a shallow cuplike indentation in the shoulder blade.
Figure 2: Joint anatomy
Ligaments bind the bones together and keep them in proper alignment. Muscles and their tendons stabilize the joint as well as move it. Cartilage, a tough and somewhat elastic tissue, provides a smooth, slippery surface for movement and cushions the joint. The viscous synovial fluid nourishes and lubricates the joint to provide frictionless movement; it’s produced by microscopic cells that line the joint called synovium. The bursae allow the soft tissues around the joint to move smoothly as the joint moves.
The immune system
Inflammation is the hallmark of a number of types of arthritis, including rheumatoid arthritis, gout, pseudogout, ankylosing spondylitis, reactive arthritis, psoriatic arthritis, enteropathic arthritis, and infectious arthritis. Such conditions all appear to stem, directly or indirectly, from an inflammatory response mediated by the immune system.
In inflammatory rheumatic diseases, the immune system reacts to elements that the body perceives as foreign. These elements could be actual invaders, such as bacteria; cell components wrongly identified as foreign; or some other trigger. Research shows that certain people may be more genetically susceptible than others to such inflammatory rheumatic diseases.
The normal immune response
The skin covering your body and the mucous membranes lining your respiratory system and gastrointestinal tract are protective barriers that keep out most of the harmful substances in the environment — including toxins and infectious microbes — that might enter your body. When there’s a breach to one of these barriers, the immune system activates special cells, proteins, and powerful chemicals to eradicate the invader. Although surveillance and policing go on quietly all the time, major confrontations can result in inflammation and tissue damage.
When bacteria, viruses, or other invaders enter the body, specialized cells release cytokines, chemical messengers that increase blood flow to the site and direct an army of white blood cells, microbe-fighters, and other protective substances to flow into the invaded tissue. Here, white blood cells release potent hormones and related substances and additional cytokines. These and other chemical mediators are responsible for intense reactions that include inflammation, which is marked by pain, redness, swelling, and heat. After the attackers have been eradicated, the immune system is no longer stimulated, and the symptoms of inflammation subside.
For this process to occur, however, the immune system must first identify the invaders as “non-self” in contrast to normal “self” cells. This requires a complex interaction of numerous recognition and signaling molecules. In simplified terms, the immune system works via several types of cells. First, cells known as phagocytes encounter the invaders, digest them, and present an antigen (a distinguishing protein or carbohydrate) on their surface (see Figure 3). The antigen binds to a special molecule called a human leukocyte antigen (HLA) complex, which in turn presents it to a second class of immune cells, launching an attack on the “non-self” invaders.
This second cell type includes several classes of lymphocytes (white blood cells). T lymphocytes recognize the antigen signal and recruit killer lymphocytes to destroy the foreign cells. At other times, T lymphocytes stimulate B lymphocytes to make antibodies, proteins that are designed especially to attack the invader. Natural killer cells and macrophages are other white blood cells involved in fighting foreign molecules. The immune system can also target body cells that become abnormal because of injury, cancerous transformation, or invasion by certain viruses.
Given this complexity, it’s not hard to imagine how autoimmune injury might occur. Antibodies made against foreign molecules might mistakenly attack normal body proteins; lymphocytes might misidentify “self” and “non-self” cells; or normal cells could get caught up in the immunological crossfire of harmful enzymes and toxic molecules.
Figure 3: Immune response
T cells attack and destroy invaders, then multiply to prepare for a future invasion.
When the system malfunctions
Inflammatory rheumatic disease occurs when something goes awry with the immune response, perhaps because B lymphocytes continue producing antibodies or because the “self” tissues are affected in some way by the original attack that makes them seem “foreign.” However it occurs, the result is an inflammatory response that continues far longer than it should.
This prolonged inflammation can be devastating. In rheumatoid arthritis, inflammation may involve internal organs as well as joints. And in ankylosing spondylitis and related disorders, inflammation often centers on a spot where tendons or ligaments attach to bone, known as an enthesis. The different patterns of tissue damage account for the symptoms that are unique to each of these ailments.
For most forms of inflammatory joint disease, the cause isn’t a single infectious agent that could affect anyone. Rather, such diseases occur through a combination of several inciting events in an individual who is genetically susceptible or predisposed at a given time by otherwise unrelated factors.
Much like fingerprints, each person’s immune response is unique. This is because a group of genes that regulate the immune system can produce responses to a very large array of potential antigens. On the short arm of chromosome 6 lies an area called the major histocompatibility complex (MHC), containing genes that underpin the immune response.
These genes function as a sort of headquarters for the immune system by determining the structure of the HLA molecules that present antigens to T lymphocytes and enable immune cells to distinguish “self” from “non-self.” They were first discovered in the 1950s when immunologists were trying to understand why organ transplants were often rejected by the recipient’s immune system. This line of research led to the discovery that people who received transplants had a better chance of recovery if certain of their HLA molecules matched the donor’s.
A number of HLA molecules are associated with particular types of inflammatory arthritis. For example, a genetic marker for HLA-B27 is present in nearly all people who have ankylosing spondylitis and in most of those with reactive arthritis, which is triggered by bacterial infection elsewhere in the body. Similarly, many people with rheumatoid arthritis have a genetic marker called HLA-DR4.
Rheumatoid arthritis is a chronic autoimmune disease in which the body’s immune system attacks healthy tissue lining the joints. It affects an estimated 1.5 million American adults. Although the disease usually first appears during middle age, onset may occur as early as a person’s 20s and 30s.
The chronic inflammation of rheumatoid arthritis begins in the synovium, where an unknown event triggers an inflammatory reaction. As a result, synovial and other cells produce a variety of chemical mediators, including cytokines and proteolytic enzymes, which together can destroy all the components of the joint. The synovial tissue also begins to proliferate, causing the normally smooth synovium to form pannus—a rough, grainy tissue that grows into the joint cavity and erodes cartilage (see Figure 1). If the tendons become inflamed, they may shorten and immobilize the joint, which can cause bone fusion and loss of mobility. If the tendons rupture, the joint may become loose or floppy.
Rheumatoid arthritis attacks multiple joints and is usually symmetrical, affecting joints on both sides of the body, particularly the finger joints, base of the thumbs, wrists, elbows, knees, ankles, or feet. It nearly always involves the wrists and the middle and large knuckles, but seldom the joints nearest the fingertips (see Figure 2). At times, joint pain may be constant, even without movement. Morning stiffness that lasts for an hour or longer is a hallmark of the disease and one of the main ways doctors gauge the severity of inflammation.
Figure 1: Joint changes in rheumatoid arthritis
The course of rheumatoid arthritis is unpredictable. Early on, the symptoms frequently abate or even disappear, only to flare up weeks or months later. Occasionally, complete remission occurs, usually within the first year. But for some people the process is destructive, ending in severe disability within a few years.
People with rheumatoid arthritis often develop eye conditions, including keratoconjunctivitis sicca (dry eye), which causes redness, burning, itching, reduced tearing, and sensitivity to light. Other complications include respiratory, heart, and neurologic disorders. In rare cases, the ligaments that tether the uppermost vertebrae (which support the skull) are damaged, allowing the vertebrae to slip out of alignment and pinch the spinal cord.
At advanced stages, rheumatoid arthritis can limit a person’s ability to carry out normal daily activities such as dressing, bathing, and walking. Those affected often experience feelings of depression and helplessness as the disease progresses. However, medications are now helping to slow the progression of rheumatoid arthritis and make a dramatic difference in the lives of many of those affected.
One of the most important steps you can take if you are diagnosed with the disease is to become an active participant in your own care. This includes working with your doctor so that you can learn to recognize flare-ups and drug side effects, take medication as prescribed, and engage in activities to maintain joint function in order to prevent disability. Balancing rest with activity, dealing with the emotional impact of rheumatoid arthritis, and using assistive devices to protect your joints against overuse are among the most helpful coping strategies. The ultimate goals in managing rheumatoid arthritis are to prevent or control joint damage, prevent loss of function, and reduce pain.
Symptoms of rheumatoid arthritis
Causes of rheumatoid arthritis
Scientists don’t know what causes rheumatoid arthritis, but they are investigating many hypotheses. The disorder runs in families, is more common among women, and may initially resemble some forms of infectious diseases, such as viral arthritis.
Genetic factors. Rheumatologists have long theorized that some insult (perhaps a microbe or an environmental toxin) triggers rheumatoid arthritis in genetically susceptible people. Recently they have linked a number of genes to the disease.
Infectious agents. Scientists have searched—without success—for evidence that people with rheumatoid arthritis might harbor certain bacteria known to cause other types of arthritis, such as Mycoplasma (which causes pneumonia or genital infections) or Chlamydia (one of several sexually transmitted organisms that can cause a condition called reactive arthritis). A more likely role for bacteria would be provoking an immune system response in which antibodies that are intended to attack the microbes also target a connective tissue protein. Other researchers believe a virus is the most likely culprit.
Figure 2: Rheumatoid arthritis of the hand
An x-ray revealing rheumatoid arthritis of the right hand.
Diagnosing rheumatoid arthritis
People who have symptoms of arthritis should have a complete medical evaluation. The symptoms and physical examination are the most important parts of the diagnostic process. The early joint symptoms of other conditions, such as lupus, are sometimes indistinguishable from those of rheumatoid arthritis, making a definitive diagnosis difficult soon after symptoms start. Blood and imaging tests are often ordered to help with diagnosis.
It may take several weeks (and several visits) before you receive a definite diagnosis. People often find this wait frustrating and worry that they are not receiving prompt treatment. But you may find it reassuring to know that a few weeks’ delay will not jeopardize your health, whereas undergoing the wrong therapy could.
Blood tests for rheumatoid arthritis
Your doctor may order several types of blood tests, because no one test is sufficient to confirm a diagnosis.
Rheumatoid factor. The majority (70% to 80%) of people with rheumatoid arthritis have rheumatoid factor in their blood, so you will probably undergo a simple blood test for this abnormal antibody. Just be aware that if rheumatoid factor is detected in your blood (that is, if the test is positive), it doesn’t necessarily mean that you have rheumatoid arthritis. About 10% of people who do not have rheumatoid arthritis will test positive for rheumatoid factor. Such people may be perfectly healthy or suffering from another disorder such as systemic lupus erythematosus. At the same time, some people with rheumatoid arthritis will test negative for rheumatoid factor. Thus your doctor is likely to order additional blood tests to look for causes of joint pain.
Anti-CCP. The anti-cyclic citrullinated peptide (anti-CCP) test measures the presence of an antibody strongly associated with rheumatoid arthritis. The anti-CCP test is gradually becoming more common. (Indeed, some rheumatologists now order it routinely whenever they order a rheumatoid factor test.) Some small, early studies have shown that the anti-CCP test can reliably help to diagnose rheumatoid arthritis in three types of people: those with early-stage disease for whom uncertainty remains about diagnosis, those with mild symptoms who test negative for rheumatoid factor, and those who test positive for rheumatoid factor but may suffer from some other condition.
ESR. The erythrocyte sedimentation rate (ESR) provides a measure of inflammation throughout the body. When there are high levels of inflammation, proteins in the blood cause the red blood cells (erythrocytes) clump more and settle faster to the bottom of a long, thin tube in this blood test. The higher the rate of sedimentation, the greater the likelihood that you are suffering from inflammation, which could be caused by rheumatoid arthritis. This test can also help determine how active your condition is.
CRP. The C-reactive protein (CRP) test also measures inflammation, but tends to change more rapidly than the ESR; minor elevations have also been associated with an increased risk of cardiovascular disease. In assessing inflammation resulting from rheumatoid arthritis, this test offers no clear advantages over the ESR test.
Imaging tests for rheumatoid arthritis
Since rheumatoid arthritis often involves the hands and feet, your doctor may also order x-rays and possibly magnetic resonance imaging (MRI) scans of these joints and others to check for bone erosions. Initial studies of MRI show that it is better at detecting bone erosions than x-rays, but its use is controversial because it may detect cysts or other bone changes that resemble erosions, and thus could lead to unnecessary treatment. The issue is important, because rheumatoid arthritis varies greatly in its progression and impact: treatment should be directed by symptoms, findings on physical examination, the results of joint imaging, and the person’s preferences, not just by the results of a single imaging test. In addition, MRI is expensive, and routine use could dramatically drive up the cost of caring for people with rheumatoid arthritis. Increasingly, ultrasound has been used to evaluate the joints of people with rheumatoid arthritis and other types of arthritis.
Rheumatoid arthritis has several relatives. All are connective tissue diseases and are considered autoimmune disorders because they are thought to originate from abnormal immune system responses. All can cause arthritis, but some have a proclivity for attacking skin and other organs. As with rheumatoid arthritis, their causes are unknown.
Systemic lupus erythematosus. Systemic lupus erythematosus (SLE) often causes a distinctive facial discoloration called butterfly rash because it appears on both cheeks and the bridge of the nose. Rashes and other skin eruptions can occur virtually anywhere on the body. SLE also affects the internal organs. Most people with the condition develop arthritis that may wax and wane in severity. Other complications may arise from immune system damage to the heart, lungs, kidneys, blood vessels, blood cells, and nervous system.
Scleroderma. This disease causes skin to thicken, tighten, and look shiny. Often, muscles atrophy. Some people have rheumatoid-like arthritis, while others have a combination of arthritis and tightening of the tendons. Scleroderma can affect the gastrointestinal tract, lungs, heart, and kidneys.
Sjögren’s syndrome. In this disease, immune system cells usually attack the tear and saliva glands, causing dry eyes and dry mouth. The disease may cause other complications, including joint pain and swelling that mimic rheumatoid arthritis.
Antibiotics for rheumatoid arthritis?
Over the years, some physicians have prescribed long courses of antibiotics to treat rheumatoid arthritis, in the belief that infection may be the source of the problem, or because an antibiotic may reduce inflammation in addition to having effects on bacteria. The infection hypothesis has never been proved, although some studies have suggested a role for bacteria as a cause of a rare form of arthritis that affects the spine and other joints but in which rheumatoid factor is not present in the blood. Although a few trials of antibiotics such as minocycline have been reported to bring about improvement, the overall benefit has been modest.
Medications for rheumatoid arthritis
In the 1990s, the treatment of rheumatoid arthritis changed significantly, as researchers developed more effective medications to fight the disease. In the past, doctors treated rheumatoid arthritis very conservatively. But evidence that joint damage starts early in the course of the disease has prompted physicians to treat it more aggressively from the beginning.
Given the complex nature of rheumatoid arthritis, and the fact that its progression varies from person to person, there are no easy answers when it comes to deciding on a treatment plan. In general, early treatment is considered the best strategy to avoid joint damage. It is also important to remember that treatment should be tailored to the individual: although some people with rheumatoid arthritis begin aggressive therapy within weeks of diagnosis, others may not need it right away.
Drugs for rheumatoid arthritis fall into several classes and may be given in combination or sequentially. Although newly approved drugs tend to generate a lot of excitement, it’s best to be cautious when using any new drug, as the true benefits and risks may not be known for years. A dramatic illustration of this was the 2004 withdrawal of the painkillers Vioxx and Bextra, then relatively new drugs, when it was discovered that people taking the pills for more than 18 months had increased cardiovascular risks. There are many reasons why such effects may not show up in the trials used in the drug approval process. Pre-approval studies are often limited in duration, while people taking the drugs for a disease like rheumatoid arthritis may take them for years. What’s more, studies may enroll no more than a few hundred or a few thousand people, who may be healthier than the tens of thousands or more who take the drug after it is approved. Uncommon side effects, interactions with other drugs, and long-term effects may only emerge in the general population in the years following approval. Unfortunately, there is no system in place to reliably identify these problems sooner. That means you need to carefully weigh the risks and benefits before deciding to try a novel therapy.
NSAIDs and steroids
To alleviate the pain and inflammation of rheumatoid arthritis, most doctors prescribe a nonsteroidal anti-inflammatory, or NSAID — either a traditional one such as ibuprofen, or the more targeted COX-2 inhibitor celecoxib (Celebrex). Although all NSAIDs can reduce pain and swelling, they have little, if any, effect on the disease process involved in rheumatoid arthritis. As a result, most people with rheumatoid arthritis need disease-modifying antirheumatic drugs (DMARDs; see below) to control disease activity.
Although NSAIDs can provide considerable benefit, they may also have a variety of side effects. If you are considering long-term use of any NSAID (including celecoxib), talk with your doctor about your personal health risks, particularly any gastrointestinal, kidney, or cardiovascular problems you may have.
Like NSAIDs, corticosteroids such as prednisone also dampen the body’s inflammatory response. But long-term use can actually damage the joints and cause other health problems such as osteoporosis, diabetes, increased susceptibility to infections, cataracts, and hypertension. Today, corticosteroids are used very cautiously. They may be injected directly into a very inflamed joint or taken orally in low doses if other drugs fail to control inflammation. High doses are reserved for rare, life-threatening crises.
Disease-modifying antirheumatic drugs alter the function of the immune system, which can slow the progression of rheumatoid arthritis. Because these medications can reduce or prevent joint damage and preserve joint function, they have become the first-line treatment and standard of care for most people with ongoing symptoms of joint damage.
DMARDs may be prescribed alone or in combination with drugs from other categories. Methotrexate (Folex, Rheumatrex, Trexall), when carefully prescribed, has an excellent safety profile, is highly effective, and is usually the first choice of therapy. It’s also the drug against which all newer agents are judged. For example, leflunomide (Arava), a newer DMARD, may be nearly as effective as methotrexate. It has a different, but acceptable, safety profile. Like methotrexate, leflunomide can lead to liver toxicity. And it shouldn’t be taken by anyone with compromised kidney function.
Other commonly prescribed DMARDs include hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine), although these are usually chosen for mild disease, in combination with methotrexate, or when methotrexate is not tolerated. Additional options include cyclosporine (Neoral) and penicillamine (Cuprimine, Depen), but these are used much less often because they appear to be less effective, less safe, or both.
Although DMARDs are often highly effective, their toxicity may extend to frequently proliferating cells that are vital to the body’s renewal processes. For example, they may have damaging effects on the bone marrow, bladder, lung, liver, intestine, and reproductive organs. Some also carry the risk of birth defects if taken by pregnant women. Anyone taking a DMARD is regularly monitored and may need to have frequent tests, including complete blood cell counts, liver function tests, and urinalyses. The specific monitoring tests and frequency of testing vary depending on the drug taken.
One thing to keep in mind is that DMARDs are slow-acting drugs. Do not become discouraged and stop taking a DMARD before it has had a chance to work. Your doctor will probably advise you to take an NSAID, a corticosteroid, or both during the early weeks or months of treatment until the DMARD begins to take effect. Failure to respond to one DMARD does not mean you will fail to respond to another.
Biological response modifiers
Biological response modifiers, also called biologics, are a type of DMARD designed to alter the function of cytokines, signaling molecules that help mount an inflammatory reaction. These drugs may be able to do what other drugs have failed to do so far: stop the rate of joint deterioration.
Anti-TNF agents. These drugs block the action of tumor necrosis factor (TNF), which appears to play a pivotal role in joint inflammation (see Figure 12). Five anti-TNF agents are now available: adalimumab (Humira), certolizumab (Cimzia), etanercept (Enbrel), infliximab (Remicade), and golimumab (Simponi). About 60% to 70% of people with rheumatoid arthritis respond well to anti-TNF agents.
Figure 3: How anti-TNF agents work
When the immune system attacks the body’s own cells, autoimmune conditions such as rheumatoid arthritis can develop, triggering inflammation and destruction of tissues. One of the chemical messengers involved in inflammation is tumor necrosis factor (TNF). TNF binds to normal joint tissues and increases inflammation (A). But an anti-TNF drug binds to the receptor sites on the joint tissue cells, blocking the TNF from causing destructive inflammation (B).
In a number of people with rheumatoid arthritis, these drugs have induced something close to remission. However, like anti-cancer chemotherapy, these drugs are potent and expensive. In addition, infliximab requires frequent visits to the hospital for infusions. As such, anti-TNF agents may be too aggressive for people with a mild or benign form of rheumatoid arthritis. And not everyone with rheumatoid arthritis responds to anti-TNF therapy. Even those who do may find their disease flares up again once therapy is stopped. For these reasons, most experts recommend that anti-TNFs be used only when first-line treatment with methotrexate or some other DMARD fails.
Anti-TNF agents are often used in combination with methotrexate to benefit people with active rheumatoid arthritis whose symptoms don’t respond to methotrexate alone. These medications are taken by intravenous infusion or injection (see Appendix for more details). Several studies have shown that people with moderate to severe disease who combine methotrexate and anti-TNF treatment have fewer symptoms and less joint destruction, especially if the treatment begins early.
In rare cases, anti-TNF therapy has been associated with long-term neurological side effects, including numbness, tingling, and weakness. These symptoms may mimic multiple sclerosis (MS), so people with MS are generally advised not to take anti-TNF drugs. These drugs have also been linked to tuberculosis (especially in people previously exposed to the infection) and fungal lung infections such as histoplasmosis. Infliximab should not be taken by anyone with heart failure.
Other immune system modulators. These five medications target different parts of the immune system to dampen inflammation. Some are given to people who haven’t responded well to DMARDs, but they are often given in combination with a DMARD (often methotrexate) to boost effectiveness.
- Abatacept (Orencia) keeps the immune system from attacking healthy tissues by interfering with T cell activation. The most common side effects with abatacept include headache, upper respiratory tract infection, sore throat, and nausea. Abatacept can also make you more vulnerable to infections (including pneumonia) or make an existing infection worse. Some people develop an allergic reaction, which takes the form of a rash and fever. If serious, the reaction may require emergency medical help.
- Anakinra (Kineret) is in a class of drugs known as interleukin antagonists. It works by blocking interleukin-1, a protein involved in the bone damage that occurs when joints are damaged by rheumatoid arthritis. Side effects include a low white blood cell count and upper respiratory infections.
- Rituximab (Rituxan), a drug originally developed to treat non-Hodgkin’s lymphoma, was later approved as a treatment for rheumatoid arthritis. Rituximab targets and helps to destroy B cells thought to become overactive when the immune system malfunctions in rheumatoid arthritis. The most common side effects include fever, shaking, chills, weakness, nausea, and headache. But some people have experienced serious adverse reactions, including shortness of breath, lung congestion, abnormal heart rhythms, and low blood pressure. In rare cases, the drug has triggered severe skin reactions or death from kidney failure.
- Tocilizumab (Actemra) belongs to a group of drugs called interleukin-6 receptor–inhibiting monoclonal antibodies. These drugs target a common protein called interleukin-6 (IL-6) that is found in all of the body’s joints and can increase inflammation. Side effects include headaches and infections, including colds and upper respiratory tract infections
- Tofacitinib (Xeljanz) is in a class of drugs called Janus kinase inhibitors. It affects the inflammatory mechanism inside cells. Tofacitinib is used for moderate to severe rheumatoid arthritis in people who do not respond to methotrexate. Side effects include diarrhea, headache, runny or stuffy nose, and sore throat.
Surgery for rheumatoid arthritis
Some people with rheumatoid arthritis require surgery to reconstruct or replace a damaged joint. Surgery is usually recommended when drug treatment alone can no longer improve the situation, although the timing of such surgery — and whether to go ahead with it — is up to you and your physician. Surgery is usually viewed as a last resort to reduce pain and improve function. One possible exception is hand surgery, as many hand surgeons advocate early surgical intervention to remove inflamed tissue and to help protect the joints and nearby tendons.
Many procedures used to repair joints damaged by osteoarthritis are also used in rheumatoid arthritis. The most common surgical procedures for rheumatoid arthritis are arthroscopy, synovectomy (removal of the inflamed tissue that lines the joint), and arthroplasty (joint repair, including joint replacement). The choice depends, in part, on which joints are involved and whether you have any other medical problems. Total joint replacement, most commonly for severe hip or knee arthritis, is a major operation and carries the associated risks. However, the benefits afforded by early DMARD treatment mean that today, fewer people need joint replacement surgery than in the past.