Rheumatoid arthritis (RA) is a chronic disease characterized by inflamed joints leading to swelling, pain, stiffness, and the possible loss of function. It occurs when the body's immune system attacks tissues (groups of cells) that make up joints. This destroys the joint's protective cartilage (the firm, rubbery tissue that cushions bones at the joints). Healthy cartilage allows bones to glide smoothly over one another. Normal cartilage also absorbs the shock of physical movement. The cartilage in those with rheumatoid arthritis breaks down and wears away. As a result, the bones rub together, causing the pain, swelling, and stiffness associated with this condition. The inflammatory process of rheumatoid arthritis is not confined to joints, but may damage other organs in the body as well. In addition, rheumatoid arthritis can occur in children, this is known as juvenile rheumatoid arthritis (JRA).
Signs and SymptomsRA usually develops slowly over time, with the following symptoms:
- Morning stiffness - waking up with stiff joints (often the wrists and base of the fingers; ankles, balls of the feet, elbows, and/or knees may also be involved)
- Joint pain with warmth, swelling, tenderness, and stiffness of the joint after inactivity
- Limited range of motion in the affected joints
- Low grade fever (when joints are acutely inflamed)
- Small, round, firm bumps (called nodules) under the skin; you can feel these, but they are generally painless
Juvenile rheumatoid arthritis, also known as Still's disease, is usually preceded by a high fever and shaking chills; a pink skin rash may also be present.
CausesMedical researchers do not know exactly why RA develops. They speculate that a combination of factors, including genetic susceptibility, an abnormal immune response, and certain changes in the body such as an infection or hormonal shift, can trigger its development.
Risk FactorsRisk factors for RA include:
- Age - although the disease can occur at any age, it generally starts in young adulthood, with peak onset between ages 25 and 55. JRA affects 50,000 children in the United States.
- Female sex - women are affected two and a half times more often than men, and have a greater chance of having a severe case
- Family history - having relatives with this type of arthritis increases your risk of getting it yourself
- Cigarette smoking – it appears that heavy smoking over a long period of time increases your risk of getting RA
- History of blood transfusions
- Coffee intake – controversial; one Finnish study reported a direct association between coffee consumption and an increased risk for RA, but the study did not account for other factors such as the way coffee is prepared in Finland (typically without filters). Further investigation in other countries is needed.
- Medication - interferon-alpha, a drug used to treat hepatitis, autoimmune diseases, and other diseases has triggered RA in rare cases
DiagnosisRheumatoid arthritis can be difficult to diagnose because it resembles many other conditions, and symptoms develop so gradually they can go unnoticed. Even after RA has been diagnosed, it is extremely important to determine how the disease is progressing in order to treat it appropriately.
Your doctor is likely to use a combination of the following methods to diagnose the disease and rule out the possibility of other causes of arthritis:
- Medical history – assessing symptoms by asking when they started and how they changed over time, including which joints are currently involved and have been affected previously. You may be asked about other medical conditions that could be contributing to current joint symptoms, and whether any factors (such as a fall or injury) could have caused these symptoms. The doctor will also determine whether you are taking might interact with drugs that he or she is considering prescribing.
- Physical exam - each of the affected joints is examined for redness and swelling, the presence of fluid in the joint, and the strength and range of motion of the joint.
- Blood tests - are performed to look for general signs of inflammation, to help eliminate the possibility of other types of arthritis such as osteoarthritis or Lyme's disease, and to check for possible markers of RA such as antibodies called rheumatoid factor that collect in the synovium (a membrane that produces joint-protecting fluid).
- Joint aspiration - fluid may be withdrawn from the joint for evaluation using a needle and syringe. The synovial fluid, as it is called, is evaluated for signs of inflammation and to eliminate other causes of your arthritis.
Treatment ApproachRheumatoid arthritis usually requires lifelong treatment, including various medications, physical therapy, education, and possibly surgery. Treatment is aimed at relieving symptoms and preserving joint function.
Regular visits to your healthcare provider will be necessary to monitor the progress of the disease and side effects of drugs you may be taking. This might also entail regular blood and urine tests.
Frequently, the disease can be controlled with a combination of treatments. Treatment may vary depending on the severity of the symptoms. Surgery may be needed, if medications fail.
For the past 10 years, studies have shown that early, aggressive treatment for RA can delay the onset of joint destruction. In addition torest, strengthening exercises, and anti-inflammatory agents, the current standard of care is to start therapy with disease-modifying anti-rheumatic drugs (DMARDs) – that is, drugs that actually alter the course of the disease rather than just relieve symptoms. Studies show that certain dietary supplements, particularly omega-3 fatty acids, show promise in helping to relieve symptoms. Other symptom-relieving measures might include bathing in sulfur baths or warm pools, applying capsaicin to the skin for pain, and having electrical stimulation to increase muscle strength.
LifestyleRange of motion exercises and individualized exercise programs prescribed by a physical therapist can help to maintain joint motion and strength and delay the loss of joint function.
Joint protection techniques, such as heat and cold treatments and splints or orthotic (straightening) devices to support and align joints, may be very helpful.
MedicationsThe following drugs are used to treat RA.
- Disease-modifying anti-rheumatoid drugs (DMARDs)—include gold compounds and methotrexate. Methotrexate is used most often, sometimes with antimalarial drugs (such as hydroxychloroquine) or sulfasalazine, and has been proven effective. DMARDs can have serious side effects such as kidney, liver, lung, or retinal damage. Other DMARDs include D-penicillamine, cyclosporine, and leflunomide.
- Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs)—reduce pain and inflammation. These include numerous over-the-counter and prescription medications such as ibuprofen, naproxen sodium, diclofenac, diflunisal, etodolac, fenoprofen, indomethacin, ketoprofen, nabumetone, oxaprozin, piroxicam, sulindac, salsalate, and tolmetin; side effects of frequent use include gastrointestinal irritation, bleeding, and ulceration.
- Cyclo-oxgenase-2 (COX-2) inhibitors—such as celecoxib and rofecoxib, reduce pain and inflammation with fewer gastrointestinal side effects than NSAIDs
- Corticosteroids—decrease inflammation and control pain; given orally or intravenously. Some potentially possibly serious side effects (such as diabetes, cataracts, osteoporosis, weight gain, and high blood pressure) are associated with this class of drugs, if used over a long time; therefore, use of corticosteroids for RA is usually limited to short courses and as low a dose as possible.
- Immune suppressants—are used for serious cases of RA when all other medications have failed. These include azathioprine and cyclophosphamide.
- Tumor necrosis factor (TNF) modifiers—such as etanercept, a new, and increasingly popular, medication, and infliximab. Both are FDA-approved for moderate to severe cases of RA. These drugs block TNFs (inflammatory proteins) and are given by intravenous injection. Etanercept reduces pain and swelling with fewer severe side effects than DMARDs; infliximab reduces symptoms of RA and in combination with methotrexate may halt progression of joint damage. TNF modifiers are associated with side effects such as severe infection.
Surgery and Other ProceduresOccasionally, surgery may be required to treat severely affected joints. The most successful surgeries are those on the knees and hips. Removal of the synovium (called synovectomy) is a common surgical procedure.
A later alternative is total joint replacement with a prosthesis (an artificial joint). Surgeries can be expected to relieve pain, correct deformities, and modestly improve joint function. In extreme cases, total knee or hip replacement can mean the difference between being completely dependent on others and having an independent life at home.
Nutrition and Dietary SupplementsDiet
In general, it is important to eat a nutritious diet full of whole foods including protein, which is needed to heal. Foods rich in the B vitamins, vitamin E, zinc, and selenium may be particularly important. Although there are claims of several types of diets being effective for rheumatoid arthritis, no one diet has been found to work for everyone.
There are reports of people with RA who experienced an improvement in their symptoms when they switched from a typical Western diet (high in animal protein and simple sugars) to a vegan diet with lots of uncooked berries, fruits, vegetables, nuts, roots, seeds, and sprouts. Vegan diets contain no animal products and obtain protein from vegetable sources.
Elimination/provocation diets (also called elimination/re-challenging diets), designed to detect allergens by systematically taking certain foods out of the diet and reintroducing them one at a time can be considered but should be strictly supervised by a qualified physician and/or dietitian. If this process is followed, you should keep careful track of your symptoms in a food diary to see if the dietary changes impact your symptoms or not.
Because supplements may have side effects or interact with medications, they should be taken only under the supervision of a knowledgeable healthcare provider.
Bromelain (Ananas comosus), found in pineapples, is a mixture of enzymes with anti-inflammatory properties. Preliminary studies suggest that bromelain may help reduce the pain associated with rheumatoid arthritis. In fact, studies of people with osteoarthritis suggest that bromelain supplements may be as effective as some commonly used nonsteroidal anti-inflammatory (NSAID) medications (such as ibuprofen and diclofenac) for reducing pain associated with this other type of arthritis. Bromelain is generally recommended for no longer than 8 to 10 days in a row. Quercetin and bromelain are often taken together.
Animal studies suggest that oral copper supplements reduce the development and progression of arthritis. Many people with RA apply copper solutions to their skin or wear copper bracelets in hopes of relieving pain and inflammation. Although reports of success with these methods are mixed, one early study did show that the copper bracelets worked better than placebo bracelets. Sweat can interfere with how well the topical copper solutions and bracelets work.
People with rheumatoid arthritis tend to have low levels of MnSOD (an antioxidant that helps protect the joints from damage during inflammation). Manganese supplementation is thought to increase MnSOD activity. Also, manganese is often combined with glucosamine and/or chondroitin, two substances often used to help treat the other major type of arthritis, osteoarthritis.
Omega-3 Fatty Acids
Extensive research indicates that omega-3 fatty acids reduce inflammation and help prevent arthritis. Omega-3s are essential fatty acids, meaning that the body requires them but must obtain them from food. Several articles reviewing the research on omega-3 fatty acids conclude that omega-3 supplements reduce tenderness in joints, decrease morning stiffness, and allow for a reduction in the amount of medication needed for people with rheumatoid arthritis.
Further, an animal study suggests that treatment with omega-3 fatty acids may reduce the risk of ulcers from nonsteroidal anti-inflammatory drugs (NSAIDs). More research is needed to determine whether this particular effect applies to people.
Good sources for omega-3 fatty acids include fish oils (from cold water oily fish) and plant oils (for example, rapeseed [canola] oil, soybeans, soybean oil, pumpkin seeds, pumpkin seed oil, flaxseeds, flaxseed oil, walnuts, and walnut oil).
Another potential source of omega-3 fatty acids is the New Zealand green lipped mussel (Perna canaliculus), used for centuries by the Maori people for good health. In a trial involving 28 people with RA, nearly 70% of those who received P. canaliculus extracts experienced the following:
- Decreased joint stiffness and pain
- Increased grip strength
- Enhanced walking pace
Omega-6 Fatty Acids
Some preliminary information indicates that gamma-linolenic acid (GLA), an omega-6 fatty acid, from evening primrose oil (EPO), borage oil, or black currant seed oil, may diminish joint pain, swelling, and morning stiffness. GLA may also allow for lower amounts of pain medication. These studies have been small in size, but nevertheless, you may want to talk to your doctor about whether using GLA is safe for you. Pay attention, over 1 to 3 months of use, to whether your symptoms get better or not. Note that some researchers theorize that borage oil may not be safe to use with non-steroidal anti-inflammatory drugs (such as ibuprofen). This theory needs to be tested.
At the same time that this particular omega-6 fatty acid (namely, GLA) may be helpful, other omega-6 fatty acids (linoleic acid, found in vegetable oils and arachidonic acid, found in meat) should be avoided because these promote inflammation.
Quercetin is a flavonoid as well as an antioxidant found in many fruits, fresh berries, and vegetables. Laboratory and animal studies suggest that quercetin has anti-inflammatory properties. In test tubes, for example, quercetin inhibits the type of inflammation that can occur in the joints of those with arthritis. Bromelain can enhance the effects of quercetin.
Selenium is an essential mineral found in tiny amounts in the body. It is also an antioxidant, and is found in fish, shellfish, Brewer's yeast, wheat germ, garlic, whole grains, sunflower seeds, and Brazil nuts. Low levels of selenium in the blood may be associated with increased risk of RA. It is not known whether supplementation with selenium alone is beneficial. Some experts believe, however, that the combination of selenium and vitamin E can relieve symptoms of RA.
Sulfur is a naturally occurring mineral found primarily near hot springs and volcanic craters. It is available in two supplement forms - dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM). Sulfur-containing mud baths (often called balneotherapy) is one of the oldest forms of therapy to relieve pain for people with arthritis, and this tradition is supported by scientific studies. Soaks in the Dead Sea, with or without mud packs, may be particularly beneficial. The benefits that you can experience from sulfur baths if you have arthritis include:
- Improved strength
- Less morning stiffness
- Decreased inflammation and swelling
- Diminished pain
Vitamin B5 (Pantothenic Acid)
Although vitamin B5 has not been widely used for RA, some researchers report that blood levels of vitamin B5 are lower in people with RA than those without this condition. A study conducted in 1980 concluded that 2,000 mg/day of calcium pantothenate (a form of vitamin B5) improved symptoms of RA including morning stiffness and pain. Further studies are needed to confirm these findings, but there may be some benefit to making sure that there is an adequate amount of vitamin B5 in your diet. Vitamin B5 is found in a wide variety of foods, such as fresh meat and vegetables and whole grains. Processed and frozen foods contain lower amounts of this vitamin.
Vitamin B6 (Pyridoxine)
Low levels of vitamin B6 have been associated with rheumatoid arthritis. This may be due to low dietary intake of vitamin B6. In addition, methotrexate and penicillamine, drugs sometimes prescribed for RA, can reduce the levels of vitamin B6 in people taking either of these medications.
Vitamin B Complex
Eating a balanced diet, including a complete vitamin B complex, is a good practice. It is not known if taking extra vitamin B5 or B6 is of any use if you have arthritis. Vitamin B9 (Folic Acid)
Methotrexate, commonly prescribed for RA, increases your body's need for folic acid. Taking a folic acid supplement decreases the side effects from the drug without reducing its effectiveness.
Vitamin D is needed to maintain healthy cartilage. Vitamin D has been shown to prevent the breakdown of cartilage in people with osteoarthritis. It is possible that adequate amounts of vitamin D may also be useful for those with RA.
Vitamin D is found in cod liver oil, fatty fish, eggs, and fortified milk and cereal. If you follow a vegan diet, don't get enough exposure to the sun, or are obese or older, you may be prone to having low levels of vitamin D and may need to take a supplement.
Additional nutrients that may prove beneficial as part of the treatment of RA if more research is conducted include:
- Antioxidants in general, vitamins C and E in particular
- Vitamin B2 (Riboflavin)
HerbsThe use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, contain active substances that can trigger side effects and interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care and only under the supervision of a practitioner knowledgeable in the field of herbal medicine.
The following have been used traditionally to treat rheumatoid arthritis:
- Burdock (Arctium lappa and other Arcticum spp)
- Goldenrod (Solidago virgaurea)
- Horsetail (Equisetum arvense)
- Lavender (Lavendula augustifolia) – used topically
- Pau d'Arco (Tabebuia avellanedae)
- Stinging nettle (Urtica dioica)
- Turmeric (Curcuma longa)
- Wild yam (Dioscorea villosa)
Other herbs that may be considered by an herbalist that do have some scientific backing include:
Black cohosh (Cimicifuga racemosa)
Preliminary studies suggest that black cohosh may help reduce inflammation associated with the two main types of arthritis, osteoarthritis and rheumatoid arthritis. In a review of scientific studies, researchers concluded that a combination of black cohosh, willow bark (Salix spp.), sarsaparilla (Smilax spp.), guaiacum (Guaiacum officinale) resin, and poplar bark (Populus tremuloides) may help relieve symptoms of osteoarthritis. Whether this same combination would be helpful for RA requires research
Capsaicin (Capsicum frutescens)
Capsaicin is the main component in hot chili peppers (also known as cayenne). Applied to the surface of the skin, it is believed to deplete stores of a substance that contributes to inflammation and pain in arthritis. Pain reduction generally begins 3 to 7 days after initially applying the capsaicin cream to the skin, but may be most pronounced after about 4 weeks of use. Wash hands well with vinegar after use and avoid touching the eyes.
Cat's claw (Uncaria tomentosa)
In a study of 40 people with RA who were taking the drugs sulfazaline or hydroxychloroquine, treatment with an extract from cat's claw for 24 weeks resulted in reduced joint pain and swelling.
Devil's claw (Harpagophytum procumbens)
Devil's claw has been evaluated for helping to treat the other main type of arthritis, osteoarthritis, and may prove to be beneficial for RA, if studied properly. For people with osteoarthritis, devil's claw appears to decrease pain, improve joint function, and reduce the amount of medications used.
Feverfew (Tanacetum parthenium)
Although many laboratory tests demonstrate anti-inflammatory properties of feverfew and many professional herbalists recommend feverfew for the treatment of arthritis, a study conducted in 1989 concluded that feverfew was no more effective than placebo in improving symptoms of rheumatoid arthritis. Some experts argue that this study was poorly designed, particularly because some patients continued, throughout the study, to use non-steroidal anti-inflammatory drugs (NSAIDs), which can interfere with feverfew and reduce its effectiveness. (NSAIDs, such as ibuprofen, are commonly prescribed or recommended for arthritis.) Until further studies are conducted, it appears that the safety and effectiveness of feverfew for people with rheumatoid arthritis has yet to be scientifically proven.
Ginger (Zingiber officinale)
Ginger extract has long been used in traditional medical practices (such as Ayurvedic and Chinese) to decrease inflammation. There have been case reports of the benefit of ginger for RA in the medical literature. In one case, a man with RA consumed fresh ginger lightly cooked in meat and vegetable dishes every day and after 3 months was completely free of pain and swelling. More research is needed before it can be said that ginger relieves the symptoms of RA.
Willow bark (Salix spp.)
This herb has been used traditionally for arthritis because it can decrease pain and reduce inflammation. In fact, it was from salicylic acid, one of the ingredients in willow bark, that aspirin was originally synthesized.
Massage and Physical TherapyExercise
It is important to maintain a balance between rest (which will reduce inflammation) and exercise (which will relieve stiffness and weakness). Studies have suggested that even as little as 3 hours of physical therapy over 6 weeks will help you if you have RA, and that these benefits are sustained.
The goal of exercise is the following:
- To maintain a wide range of motion
- To increase strength, endurance, and mobility
- Improve general health
- Promote well-being
- If you feel sharp pains while exercising, stop immediately.
- If lesser aches and pains continue for more than 2 hours afterwards, then try a lighter exercise program for a while.
- Using large joints instead of small ones for ordinary tasks can help relieve pressure. For example, use your hip to close doors or the palm of your hand to push buttons.
- Balneotherapy (Hydrotherapy or spa therapy)
- Improving range of joint motion
- Increasing muscle strength
- Eliminating muscle spasm
- Enhancing functional mobility
- Easing pain
A variety of mechanical devices, called orthoses, are available for people with RA to help support and protect joints. Made from lightweight metal leather, elastic, foam, and plastic, orthoses allow some movement within the affected joint and do not restrict nearby joints. For example, splints or braces help align joints and properly distribute weight. Shock-absorbing soles in shoes can help in daily activities and during exercise. These mechanical aids are used most frequently to treat arthritic hands, wrists, knees, ankles, and feet. Orthoses should be custom-fitted by a physical or occupational therapist.
Another potentially helpful aid is compression gloves. Two studies on the overnight use of compression gloves (close-fitting nylon-spandex gloves) concluded that the gloves reduced pain and stiffness in people with RA in the fingers.
Other possibilities for symptom relief include:
- Transcutaneous nerve stimulation (TENS) - small studies show that at 70Hz, TENS, a technique used by many physical therapists, may provide short-term pain relief for people with RA.
- Magnetic devices - devices employing static magnetic fields may help reduce pain
- Heat and cold applications - some people find these applications comforting; may reduce pain
Recent trials evaluating the use of homeopathy in the treatment of rheumatoid arthritis found that the remedies were no more effective than placebo in reducing symptoms. These studies contradict an older trial that showed beneficial effects with homeopathic treatment. Despite the lack of definitive evidence, professional homeopaths might recommend one of the following treatments for RA based on their knowledge and clinical experience, as well as successful trials for homeopathy to treat another type of arthritis, namely osteoarthritis. Before prescribing a remedy, homeopaths take into account an individual's constitutional type. In homeopathic terms, a person's constitution is his or her physical, emotional, and intellectual makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for a particular individual.
Potential remedies include:
- A topical homeopathic gel containing comfrey (Symphytum officinale), poison ivy (Rhus toxicodendron), and marsh-tea (Ledum palustre)
- A combination homeopathic preparation containing R. toxicodendron, Arnica Montana (arnica), Solanum dulcamara (climbing nightshade), Sanguinarra Canadensis (bloodroot), and Sulphur
- A liquid homeopathic preparation containing R. toxicodendron, Causticum (potassium hydrate), and Lac vaccinum (cow's milk).
Chronic pain and disability can make daily functioning difficult. A holistic approach to your care may positively affect both your lifestyle and how you feel overall. Many people report that relaxation techniques, such as guided imagery and meditation, are an important part of general care and help to alleviate pain and other symptoms of RA.
Traditional Chinese MedicineTai Chi
This gentle exercise program practiced in China for centuries has been shown to produce a number of benefits, including the following:
- Improved fitness
- Increased muscular strength
- Enhanced flexibility
- Reduced percentage of body fat
- Diminished risk of falls in the elderly
- Overall sense of quality of life
- Diminished feelings of stress/tension
- Increased satisfaction with general health
- Decreased fatigue
- Easier self management of arthritis symptoms
- These benefits are likely to apply to individuals with RA as well.
Borage seed oil, and possibly other sources of gamma-linolenic acid (GLA), should not be used during pregnancy because they may be harmful to the fetus and induce early labor. Pregnant or breastfeeding women should also not take goldenrod.
Warnings and Precautions Omega-6 fatty acid supplements should not be used if you have a seizure disorder because there have been reports of these inducing seizures.
Stinging nettle may enhance the effect of NSAIDs. Although the combination of stinging nettle and NSAIDs may be beneficial for the treatment of arthritic conditions, a knowledgeable healthcare provider should be consulted before adding this herb to an existing medication regimen.
Prognosis and ComplicationsRA is associated with the following joint-related complications:
- Deformities - these can result from cartilage destruction, bone erosions, and tendon inflammation and tears; such deformities can interfere considerably with even ordinary, daily tasks.
- RA involving the neck called the cervical spine) - can be life-threatening if these neck joints become unstable
- Rheumatoid nodules - painless, hard, round or oval masses that appear under the skin, usually on pressure points, such as the elbow or Achilles tendon. Occasionally, they appear in the eye where they sometimes cause inflammation. If they occur in the lungs, inflammation of the lining of the lung (called pleuritis) may occur, causing shortness of breath.
- Anemia and other blood abnormalities – anemia may occur due to failure of the bone marrow to produce enough new red cells to make up for the lost ones. Iron supplements will not usually help this condition because iron utilization in the body becomes impaired.
- Rheumatoid vasculitis (inflammation of the blood vessels) - a serious, sometimes life-threatening, complication. It can lead to open sores (ulcers) on the skin that may become infected, bleeding stomach ulcers, and neuropathies (nerve problems causing pain, numbness or tingling). Vasculitis may also affect the brain, and heart causing strokes, heart attacks, or heart failure.
- Other Heart complications – also caused by inflammation Including inflammation of the outer lining of the heart (called pericarditis) and possibly the heart muscle (called myocarditis). Both of these conditions can lead to congestive heart failure characterized by shortness of breath and fluid accumulation in the lung.
- Lung complications - can be caused by the growth of fibrous tissue in the lungs or by inflammation of the lining of the lung (pleuritis). Pulmonary nodules, as described earlier, can also develop.
- Eye complications - include inflammation of various parts of the eye.
Remission is most likely to occur in the first year and then likelihood decreases over time. Ten to 15 years after the initial diagnosis, about 20% of people will have had remission and most people will still be able to look after themselves.
Although complications may shorten the life expectancy of people with RA, treatment is constantly improving and the occurrence of severe disability and life-threatening complications appears to be decreasing.
Al-Harbi MM, Islam MW, Al-Shabanah OA, Al-Gharably NM. Effect of acute administration of fish oil (omega-3 marine triglyceride) on gastric ulceration and secretion induced by various ulcerogenic and necrotizing agents in rats. Food Chem Toxicol. 1995;33(7):555-558.
Ang-Lee M, Moss J, Yuan C. Herbal medicines and perioperative care. JAMA. 2001;286(2):208-216.
Asseth J, Haugen M, et al. Rheumatoid arthritis and metal compounds—perspectives on the role of oxygen radical detoxification. Analyst. 1998;123:3–6.
Belch JJ, Hill A. Evening primrose oil and borage oil in rheumatologic conditions. Am J Clin Nutr. 2000;71(1 Suppl):352S-356S.
Berman BM, Swyers JP, Ezzo J. The evidence for acupuncture as a treatment for rheumatologic conditions. Rheum Dis Clin N Amer. 2000;26(1):103-115.
Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston, Mass: Integrative Medicine Communications; 1998:121, 135, 150-151, 138, 226-227.
Chopra A. Ayurvedic Medicine and arthritis. Rheum Dis Clin North Am. 2000;26(1):133-144.
Chrubasik S, Enderlein W, Bauer R, Grabner W. Evidence for antirheumatic effectiveness of Herba Urticae dioica in acute arthritis: A pilot study. Phytomedicine. 1997;4:105–108.
Danao-Camara TC, Shintani TT. The dietary treatment of inflammatory arthritis: case reports and review of the literature. Hawaii Med J. 1999;58(5):126-131.
Dash M, Telles S. Improvement in hand grip strength in normal volunteers and rheumatoid arthritis patients following yoga training. Indian J Physiol Pharmacol. 2001;45(3):355-360.
David J, Townsend R, Sathanathan R, Kriss S, Dore CJ. The effect of acupuncture on patients with rheumatoid arthritis: a randomized, placebo-controlled cross-over study. Rheumatology. 1999;38:864-869.
Deal CL, Schnitzer TJ, Lipstein E, et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther. 1991;13(3):383-395.
Diagnosis. Ada Health. Accessed at https://ada.com/ on November 2, 2018.
Elkayam O, Ophir J, Brener S, Paran D, Wigler I, Efron D, Even-Paz Z, Politi Y, Yaron M. Immediate and delayed effects of treatment at the Dead Sea in patients with psoriatic arthritis. Rheumatol Int. 2000;19(3):77-82.
el-Ghazaly M, Khayyal MT, Okpanyi SN, Arens-Corell M. Study of the anti-inflammatory activity of Populus tremula, Solidago virgaurea and Fraxinus excelsior. Arzneimittelforschung. 1992;42(3):333-336.
Ernst E. Complementary and alternative medicine in rheumatology. Baillieres Clin Rheumatol. 2000;14(4):731-749.
Ernst E, Chrubasik S. Phyto–anti-inflammatories. A systematic review of randomized, placebo-controlled, double-blind trials. Rheum Dis Clin North Am. 2000;26(1):13-27.
Friso S, Jacques PF, Wilson PW, Rosenberg IH, Selhub J. Low circulating vitamin B(6) is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels. Circulation. 2001;103(23):2788-2791.
Garfinkel M, Schumacher HR, Jr. Yoga. Rheum Dis Clin North Am. 2000;26(1):125-132.
Garfinkel MS, Schumacher HR, Husain A, Levy, M, Reshetar RA. Evaluation of a yoga based regimen for treatment of osteoarthritis of the hands. J Rheumatol. 1994;21:2341-2343.
Gruenwald J, Brendler T, Jaenicke C, et al., eds. PDR for Herbal Medicines. Montvale, NJ: Medical Economics Co; 1998:810.
Guardia T, Rotelli AE, Juarez AO, Pelzer LE. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin, and hesperidin on adjuvant arthritis in rat. Farmaco. 2001;56(9):683-687.
Hafstrom I, Ringertz B, Spangberg A, et al. A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford). 2001;40(10):1175-1179.
Halpern GM. Anti-inflammatory effects of a stabilized lipid extract of Perna canaliculus (Lyprinol). Allerg Immunol (Paris). 2000;32(7):272-278.
Hanninen, Kaartinen K, Rauma AL, et al. Antioxidants in vegan diet and rheumatic disorders. Toxicology. 2000;155(1-3):45-53.
Hines Burnham, et al, eds. Drug Facts and Comparisons. St. Louis, MO: Facts and Comparisons; 2000:18.
Hutchinson D, Shepstone L, Moots R, Lear JT, Lynch MP. Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA. Ann Rheum Dis. 2001;60(3):223-227.
Kast RE. Borage oil reduction of rheumatoid arthritis activity may be mediated by increased cAMP that suppresses tumor necrosis factor-alpha. Int Immunopharmacol. 2001;1(12):2197-2199.
Kirsteins AE, Dietz F, Hwang SM. Evaluating the safety and potential use of a weight-bearing exercise, Tai-Chi Chuan, for rheumatoid arthritis patients. Am J Phys Med Rehabil. 1991;70(3):136-141.
Klein G, Kullich W. Short-term treatment of painful osteoarthritis of the knee with oral enzymes. A randomized, double-blind study versus diclofenec. Clin Drug Invest. 2000;19(1):15-23.
Klein-Galczinsky C. [Pharmacological and clinical effectiveness of a fixed phytogenic combination of trembling poplar (Populus tremula), true goldenrod (Solidago virgaurea) and ash (Fraxinus excelsior) in mild to moderate rheumatic complaints.] [in German]. Wien Med Wochenschr. 1999;149(8-10):248-253.
Kneckt P. Serum selenium, serum alpha-tocopherol, and the risk of rheumatoid arthritis. Epidemiology. 2000;11(4):402-405.
Kremer JM. N-3 fatty acid supplements in rheumatoid arthritis. Am J Clin Nutr. 2000;(suppl 1):349S-351S.
Leventhal LJ, Boyce EG, Zurier RB. Treatment of rheumatoid arthritis with black currant seed oil. Br J Rheumatol. 1994;33(9):847-852.
Lineker SC, Bell MJ, Wilkins AL, Badley EM. Improvements following short term home based physical therapy are maintained at one year in people with moderate to severe rheumatoid arthritis. J Rheumatol. 2001;28(1):165-168.
Little C, Parsons T. Herbal therapy for treating rheumatoid arthritis. Cochrane Database Syst Rev. 2001;(1):CD002948.
Man SC, Baragar FD. Preliminary clinical study of acupuncture in rheumatoid arthritis. J Rheumatol. 1974;1:126.
Martin RH. The role of nutrition and diet in rheumatoid arthritis. Proc Nutr Soc. 1998;57(2):231-234.
Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther. 1982;4(6):423-440.
Mazzetti I, Grigolo B, Borzai RM, Meliconi R, Facchini A. Serum copper/zinc superoxide dismutase levels in patients with rheumatoid arthritis. J Clin Lab Res. 1996;26(4):245-249.
Minocycline. NMIHI. Accessed at http://www.nmihi.com/m/minocycline.html on June 22, 2018.
McDougall J, Bruce B, Spiller G, Westerdahl J, McDougall M. Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis. J Altern Complement Med. 2002;8(1):71-75.
McKnight PT, Kwoh CK. Randomized, controlled trial of compression gloves in rheumatoid arthritis. Arthritis Care Res. 1992;5(4):223-227.
Milanino R, Marrella M, Crivellente F, Benoni G, Cuzzolin L. Nutritional supplementation with copper in the rat. Effects on adjuvant arthritis development and on some in vivo- and ex vivo-markers of blood neutrophils. Inflamm Res. 2000;49(5):214-223.
Mulherrin DM, Thurnham DI, Situnayake RD. Glutathione reductase activity, riboflavin status, and disease activity in rheumatoid arthritis. Ann Rheum Dis. 1996;55:837-840.
Mur E, Hartig F, Eibl G, Schirmer M. Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of uncaria tomentosa for the treatment of rheumatoid arthritis. J Rheumatol. 2002;29(4):678-681.
Naproxen. NMIHI. Accessed at http://www.nmihi.com/n/naproxen.html on June 22, 2018.
Pattrick M, Heptinstall S, Doherty M. Feverfew in rheumatoid arthritis: a double-blind, placebo controlled study. Ann Rheum Dis. 1989;48:547–549.
Pasquier C, Mach PS, Raichvarg D, Sarfati G, Amor B, Delbarre F. Manganese-containing superoxide-dismutase deficiency in polymorphonuclear leukocytes of adults with rheumatoid arthritis. Inflammation. 1984;8:27–32.
Prednisone. NMIHI. Accessed at http://www.nmihi.com/p/prednisone.html on June 22, 2018.
Randall C, Meethan K, Randall H, Dobbs F. Nettle sting of Urtica dioica for joint pain – an exploratory study of this complementary therapy. Complement Ther Med. 1999;7(3):126-131.
Rheumatoid Arthritis. MedlinePlus. Accessed at https://medlineplus.gov/ on November 2, 2018.
Rheumatoid arthritis. NMIHI. Accessed at http://www.nmihi.com/a/rheumatoid-arthritis.htm on June 22, 2018.
Riehemann K, Behnke B, Schulze-Osthoff K. Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy, inhibit the proinflammatory transcription factor NF-kappaB. FEBS Lett 1999;442(1):89-94.
Rosenstein ED. Topical agents in the treatment of rheumatic disorders. Rheum Dis Clin N Am. 1999;25(4):899-918.
Rothman D, DeLuca P, Zurier RB. Botanical lipids: effects on inflammation, immune responses, and rheumatoid arthritis. Semin Arthritis Rheum. 1995;25(2):87-96.
Segal NA, Toda Y, Huston J, et al. Two configurations of static magnetic fields for treating rheumatoid arthritis of the knee: a double-blind clinical trial. Arch Phys Med Rehabil. 2001;82(10):1453-1460.
Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr. 1999;70(3 suppl):560S-569S.
Srivastava KC, Mustafa T. Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. Medical Hypotheses. 1992;39:343-348.
Struthers GR, Scott DL, Scott DG. The use of 'alternative treatments' by patients with rheumatoid arthritis. Rheumatol Int. 1983;3(4):151-152.
Sukenik S, Buskila D, Neumann L, Kleiner-Baumgarten A, Zimlichman S, Horowitz J. Sulphur bath and mud pack treatment for rheumatoid arthritis at the Dead Sea area. Ann Rheum Dis. 1990;49(2):99-102.
Sukenik S, Neumann L, Flusser D, Kleiner-Baumgarten A, Buskila D. Balneotherapy for rheumatoid arthritis at the Dead Sea. Isr J Med Sci. 1995;31(4):210-214.
von Kruedener S, Schneider W, Elstner EF. A combination of Populus tremula, Solidago virgaurea and Fraxinus excelsior as an anti-inflammatory and antirheumatic drug. A short review. Arzneimittelforschung. 1995;45(2):169-171.
West Sk, Oosthuizen JM. Melatonin levels are decreased in rheumatoid arthritis. J Basic Clin Physiol Pharmacol. 1992;3(1):33-40.
Willer B, Stucki G, Hoppeler H, Bruhlmann P, Krahenbuhl S. Effects of creatine supplementation on muscle weakness in patients with rheumatoid arthritis. Rheumatology. 2000;39(3):293-298.
What is rheumatoid arthritis? Cleveland Clinic. Accessed at https://my.clevelandclinic.org/ on November 2, 2018.
Zurier RB, Rossetti RG, Jacobson EW, et al. Gamma-linolenic acid treatment of rheumatoid arthritis: a randomized, placebo-controlled trial. Arthritis Rheum. 1996;39:1808-1817.