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Rheumatoid Arthritis

What is rheumatoid arthritis?  What are the causes?

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation of the joints and may cause inflammation of other tissues in the body.   The immune system consists of the cells and proteins in our bodies that fight infections.  An autoimmune disease occurs when our immune system doesn’t recognize part of our body and attacks it as if it were an invader such as a bacteria or virus.  In rheumatoid arthritis, the immune system targets synovial membrane and attacks it.  The synovial membrane is secretes synovial fluid into the joint.  Synovial fluid is the joint fluid that lubricates and nourishes the joint.  Other tissues can also be targeted by the immune system in rheumatoid arthritis, but the synovium, or synovial membrane, is generally the primary target.  When the synovial membrane is attacked, it becomes inflamed (synovitis) and can thicken and erode.  As the synovial membrane is destroyed, the synovial fluid fluid is also destroyed because it is not being secreted.  The surrounding structures can also become involved leading to the joint deformities that can be seen in rheumatoid arthritis.

Rheumatoid arthritis is a debilitating and common disease, affecting approximately 1% of the population.   Women are affected three times as often as men.  It is not clear exactly what causes or triggers the autoimmune response.   Many researchers believe that a bacterial, viral, or fungal infection may trigger the autoimmune response.  Other researchers believe there is a genetic role in the development of rheumatoid arthritis. Despite active research, the question of what causes rheumatoid arthritis remains a debated topic.  Whatever the trigger or underlying cause, it has been shown that rheumatoid arthritis is an autoimmune disease.  The course of rheumatoid arthritis is often relapsing and remitting, meaning that a person can suffer with symptoms for a prolonged period of time (perhaps months or years) and then the symptoms go away for a while (perhaps years) only to recur again at a later date.   The severity and chronicity of rheumatoid arthritis varies from person to person.  Most people who develop rheumatoid arthritis will do so between the ages of 20 and 60.  In general, the earlier that symptoms develop, the more severe the disease will be.  

How is rheumatoid arthritis diagnosed?

There is no single test that can diagnose rheumatoid arthritis.  Instead, your physician must look at your entire history, physical examination, laboratory tests and radiographs when making the diagnosis of rheumatoid arthritis.  

The first step your doctor will take when diagnosing rheumatoid arthritis is take a complete medical history from you.  Your age is an important factor when considering the diagnosis.  Because most people who develop rheumatoid arthritis are between the ages of 20 and 60, if you fall outside of this age range it makes the diagnosis less likely.  Common symptoms from rheumatoid arthritis include morning stiffness that lasts for longer than one hour, bilateral symmetrical involvement of small joints (e.g. both hands), and multiple joints being involved (often 3 or more).  The most common joints to be involved are the fingers, hands, wrists, and feet.  Often, people with rheumatoid arthritis may also complain of general fatigue, weakness, low-grade fever without an obvious source of infection, decreased appetite, weight loss, and/or muscle pain.  People with rheumatoid arthritis typically will complain of difficulty performing tasks of daily living such as writing, preparing food, grasping a cup, getting dressed, and turning a doorknob.  

Occasionally, rheumatoid arthritis can affect the heart (pericarditis) in which case the person may have chest pain that is worse when taking a deep breath or when lying down.  Almost any organ in the body can become affected by rheumatoid arthritis.  When the blood vessels themselves are involved, a vasculitis develops that can be debilitating and dangerous.   These complications are more common with long-standing chronic rheumatoid arthritis.

Patients with rheumatoid arthritis will typically not have pain or swelling in the finger joint closest to the fingertip (the distal interphalangeal joint).  The other joints in the hand are often affected.  The affected joints are often tender to the touch.  Depending on how long the person has been having symptoms, and the severity of the rheumatoid arthritis, there may also be some deformity in the fingers, hands, wrists, and other joints.  Rheumatoid nodules may develop and be felt as firm lumps beneath the skin.  These occur most commonly at points of pressure under the elbow and on the fingers.  Usually rheumatoid nodules do not cause pain but they can become infected or put pressure on a nerve in which case they would need to be treated.

Your doctor will likely order several tests.  Blood tests will reveal an anemia (decreased hemoglobin) in 80% of patients with rheumatoid arthritis.  The erythrocyte sedimentation rate (ESR) is a general marker of inflammation and is elevated in 90% of patients.  In 70% of rheumatoid arthritis a marker called rheumatoid factor (RF) will be present.  However, all of these tests are nonspecific and may be positive in people without rheumatoid arthritis.  The results of these tests need to be integrated by your physician with your other findings to make the diagnosis of rheumatoid arthritis.

On radiographs (x-ray), the typical findings of rheumatoid arthritis include cysts, osteopenia, swelling, bony erosions, narrowed joint space, deformities, and fractures.  

Your physician may perform an arthrocentesis of the affected joint or joints.  This procedure involves putting a needle under sterile conditions into the affected joint and aspirating the fluid.  The fluid is then sent for analysis.  This procedure is used in this setting to rule out other possible etiologies of the pain and swelling such as infection, gout, and pseudogout.  

In a person with suspected rheumatoid arthritis and neck pain or neurologic symptoms (pain, numbness, weakness radiating into the arms or legs), the physician should perform tests to ensure that there is no instability of the cervical spine (vertebrae in the neck) because people with rheumatoid arthritis are more susceptible to this type of instability than the general population.

How is rheumatoid arthritis treated?

            There is no cure for rheumatoid arthritis.  However, several treatments exist to decrease the symptoms of rheumatoid arthritis and greatly improve quality of life.  

            Early diagnosis: The sooner that rheumatoid arthritis is treated, the better.  If you think you might have rheumatoid arthritis, or other type of arthritis, don’t delay in getting to your doctor.  Prolonging treatment only makes it more difficult to treat later.  

Diet: One of the simplest treatments, and yet a treatment that has been found to be effective for many people, is consuming an anti-inflammatory diet.  Primarily, this consists of consuming omega-3 fatty acid containing foods, including small cold water fish, fruits, and vegetables.  See the section on diet and nutrition for more details.

Weight loss:  As with other forms of arthritis, if you are overweight then losing weight can make a large impact on decreasing pain and stiffness in your joints by taking some of the pressure off of them.  

Exercise and rest:  Rest is an important part of treating rheumatoid arthritis.  One of the symptoms of rheumatoid arthritis can be fatigue as well as a sense of generalized malaise.  It is important to get adequate rest so that your body does not get run down, This is true for everyone, but particularly true for people with rheumatoid arthritis. People with rheumatoid arthritis should not exercise to the point of exhaustion.  Rather, they should take frequent breaks and rest before they get too tired.   

While rest is important, it is also important to stay active and participate in an exercise regimen.  The exercise regimen should include cardiovascular exercise (bicycling, swimming, etc), stretching, and strengthening exercises.  Your physician can provide you with a structured exercise program tailored to your individual needs.  Ideally, the exercise program should include exercises such as swimming that do not load the joints with too much pressure.  It is very important to promote flexibility in the joints and move each joint through its full range of motion at least once a day.  

Physical therapy:  It is important to be enrolled in a well-structured physical therapy program.  In addition, physicians and physical therapists can fit you for gait aids (e.g. cane) when necessary.

Occupational therapy:  Because rheumatoid arthritis affects the small joints of the wrist, hand, and fingers, as well as other joints, it can make activities of daily living difficult.  Occupational therapists specialize in helping patients overcome these difficulties and perform their activities of daily living.  A structured program with an occupational therapist can include learning proper body biomechanics, developing strategies to perform activities despite limitations, the use of splints to aid in tasks (e.g. hand splints, wrist splints), and other ways to use healthier body parts to compensate for body parts that are more affected by the disease process.  Splints are also helpful in maintaining proper joint alignment.

Modalities:  Physicians, chiropractors, physical therapists, and occupational therapists may use a variety of modalities to help reduce symptoms.  These modalities include ice, heat, massage, ultrasound, warm wax, and electrical stimulation.

Oral medications:  There are two basic lines of oral medication treatment for rheumatoid arthritis.  First-line treatment is used for acute inflammation and pain.  These medications include non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, naproxen, and etodolac.  The most common side effect from this class of medication is abdominal problems such as stomach pain, ulcers, and bleeding in the gastrointestinal tract.  Combining these medications with stomach protecting medicines like sucralfate and misoprostol can reduce the risk of stomach problems.  A proton‑pump inhibitor medication such as omeprazole or pantoprazole (e.g. Prevacid, Protonix), can also be helpful to reduce the risk of stomach problems.  

Steroids are also considered a first line treatment for rheumatoid arthritis.  Steroids can be taken orally or injected directly into an affected joint.  Long-term corticosteroid treatment carries a significant number of risks including easy bruising, cataracts, increased risk of infection, skin necrosis, osteoporosis and muscle wasting.  The risk of osteoporosis can be decreased by taking supplements of calcium and vitamin D.  The risk of increased infection rates can be reduced by gradually tapering off steroids instead of abruptly stopping taking high-dose steroids (which can also result in an acute flare up of the rheumatoid arthritis).  

Second-line medications include disease-modifying anti-rheumatic drugs (DMARDs).  These medications are not anti-inflmmatory medications but they do promote remission of the disease.  DMARDs are taken chronically for months or years.  They generally take longer to be effective than first-line drugs.  Depending on the response of the individual, more than one DMARD may be used at a time.  While reserved as second-line therapy, many physicians believe that the sooner DMARDs are used, the better the response.

DMARDs include hydroxycholoquine, sulfasalzine, methotrexate, D-penicillamine, gold salts, azathioprine, and cyclophosphamide.  Plaquenil is an anti‑malarial medication that has been found to be helpful.  Patients taking plaquenil should be monitored by an opthamologist because there is a small but increased risk of developing vision changes. Other side effects include skin rashes, muscle weakness, stomach problems.  

Sulfasalzine is a medication that is typically used for inflammatory bowel disease (e.g. ulcerative colitis, Crone’s disease).  It has been found to be useful for rheumatoid arthritis.  Skin rash, headache, nausea, fever, and stomach problems are the most common side effects. People with sulfa allergy should not take sulfasalzine.  People with gastrointestinal or genitourinary obstruction should also not take this drug.  

Methotrexate is an immunosuppressive drug that has also been shown to effective in rheumatoid arthritis.  It is better tolerated than some of the other DMARDs but side effects include stomach problems, malaise, fatigue, fever, increased infection rate, and chills.  Because of the small risk of bone marrow or liver dysfunction, all patients on this drug require regular blood testing.  Azathioprine, cyclophosphamide, and other immunosuppressive drugs are generally reserved for severe, recalcitrant cases of rheumatoid arthritis because of the potential for serious side effects.   

D-penicillamine is also used to treat rheumatoid arthritis. Side effects include fever, chills, mouth sores, skin rash, and kidney and bone marrow damage.  Gold salts used to be used more frequently than at present.  The large number of side effects of gold salts have made them less attractive than other DMARDs.  Nevertheless, in select patients they may be helpful.  

Anti-TNF alpha factor medications have recently emerged as a newer class of medication for the treatment of rheumatoid arthritis.  In many patients, this class of drug has been extremely helpful.  Etanercept, infliximab, and adalimurnab are all members of this class of drug.  TNF alpha is a potent inflammatory mediator.  TNF alpha is released from damaged cells and essentially acts like a beacon calling other inflammatory cells to come to the site.  Anti-TNF alpha medications stop TNF alpha from calling to other inflammatory cells and so they help break the inflammatory cycle.  Etanercept is injected under the skin either once or twice a week.  Infliximab is given intravenously, and adalimumab is injected weekly or every other week.  Anti-TNF alpha medications may cause stomach problems, nausea, vomiting, upper respiratory infection symptoms, and skin rash.  Anti-TNF alpha medications are typically reserved for patients who have not responded to DMARD therapy.  Once anti-TNF alpha therapy is begun, DMARDs are also often used in conjunction.

Injections:  Local injections of cortisone are often effective in treating symptomatic joints.  The bursae that cover and protect joints are also more commonly inflamed in rheumatoid arthritis.  These bursae also can be injected with cortisone to reduce the inflammation and pain.  Research is currently underway at academic institutions into injecting anti-TNF alpha medication directly into the affected joints.  However, this is currently an investigational treatment.

Surgery:  When joints become very symptomatic, interfere with activities of daily living and quality of life, and when these joints do not respond to more conservative treatments, surgical intervention can be considered.  Depending on the joint and degree of involvement, multiple surgical options are available.  A thorough discussion of all the potential risks and benefits should be pursued with your doctor.  Total hip replacement and total knee replacement are considered when the hip and knee are involved, respectively.

            Author: Grant Cooper, M.D., Department of Physical Medicine and Rehabilitation, New York-Presbyterian Hospital, The University Hospital of Columbia and Cornell, New York City, NY

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