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Rheumatoid Arthritis: Treatment & Medication
Updated: Apr 5, 2009
- Overview
- Differential Diagnoses & Workup
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Treatment
Rehabilitation Program
Physical Therapy
The goals of rehabilitation for patients with rheumatoid arthritis (RA) include pain relief, increased range of motion (ROM), increased strength and endurance, prevention and correction of deformities, and provision of various counseling and educational services. Numerous nonpharmacologic methods are available to the physiatrist to assist patients in achieving these goals. These methods include therapeutic modalities, splints and orthotics, assistive device equipment, joint protection and energy conservation techniques, and education and therapeutic exercise programs.5
Therapeutic modalities
Heat, either superficial or deep, is an effective modality for the relief of joint pain and stiffness caused by RA. In addition, it is also used to treat joints in preparation for ROM, stretching, and muscle strengthening exercises. Heat may be administered via moist hot packs, electric mittens, a hot shower, spas, ultrasonography, diathermy, or paraffin. Superficial and deep heating methods have been shown to raise the intra-articular temperature in patients with RA.
Cold is preferable for treatment of an acutely inflamed joint. Application of cold results in decreased pain and decreased muscle spasm. Cold may be delivered via ice packs, ice sticks, topical sprays, or ice water.
Splints and orthotics
Orthotic devices play an important role in the rehabilitation management of patients with RA. These devices are used to decrease pain and inflammation, improve function, reduce deformity, and correct biomechanical malalignment.
Lower extremity orthoses are prescribed to provide stability and proper alignment or to shift weight bearing off the affected limb. The most common orthoses used for the lower extremity involve the foot and ankle joints. Approximately 80% of patients affected with RA illustrate significant foot involvement. These problems are easily accommodated by providing a deep, wide, soft leather shoe. A metatarsal pad or bar is typically used to remove weight from painful MTP joints, and a rocker-bottom sole can be used to facilitate roll-off. Hindfoot pronation should be addressed with custom inserts. Finally, knee orthoses may be used to control edema, pain, patellar alignment, hyperextension, or collateral or cruciate ligament instability.
Therapeutic exercise
Fatigue and decreased endurance are frequent symptoms in patients with RA. When comparing these patients to age-matched subjects without RA, a reduction in aerobic capacity and muscle strength is noted. This reduction is due to the disease itself and to the lack of physical activity in these patients. Exercise is an important part of the rehabilitation management of RA.
Aerobic conditioning in patients with RA (if tolerated) improves maximum oxygen uptake and decreases perceived exertion at submaximal workloads. At the same time, no adverse effects have been noted in the joints of these patients. In addition, patients undergoing long-term endurance training have been known to feel less isolated, to take less sick leave, and to develop improved function in activities of daily living (ADL). Thirty minutes of daily aerobic exercise, several times each week, should be encouraged in patients with well-controlled RA.
Muscle atrophy often accompanies RA and is exacerbated by inactivity, bed rest, splints, and medications. Isometric exercises restore and maintain strength in patients with RA without producing pain. Resistance exercises may be initiated when the isometric program has been well established and when the patient is free of pain.
Occupational Therapy
Occupational therapy also can be very useful for patients with rheumatoid arthritis (RA).5 An occupational therapist may work in conjunction with the physical therapist to ensure that the patient is able to meet his or her goals. An occupational therapist may also assist in the recommendation and use of splints and orthotics, especially when the upper extremity is affected. Upper extremity orthoses may be classified as either static or dynamic. Static splints are used to support a weak or unstable joint, to rest a joint for pain relief, or to maintain functional alignment. Dynamic splints traditionally have been used to manage the postoperative hand, but they also may be used to increase manual dexterity. The most commonly used splints for the hand are the finger-ring splints and the thumb-post splint. The functional wrist splint and the resting hand splint are commonly used for wrist splinting.
Adaptive equipment
Many assistive devices are available to patients with RA and are used to provide maximal function, maintain independence, reduce joint stress, conserve energy, and provide pain relief. Equipment is available to assist patients with transfers, dressing, feeding, toileting, cooking, and ambulation.
Joint protection education
Joint protection education provides the patient with techniques and recommendations for the prevention of joint overuse and the avoidance of biomechanical torques that excessively bend the joint.5 The use of adaptive equipment is important. Other components of a good joint protection program include maintenance of good posture, avoidance of overuse during inflammation, modification of tasks to decrease joint stress, and use of appropriate splints.
Energy conservation education
Fatigue is a major component of RA and is due to the systemic nature of the disease, as well as to the decreased cardiovascular endurance observed in patients with this inflammatory disorder.
The goal of energy conservation techniques is to save energy while maximizing function. Adaptive equipment is an essential part of this program. Other elements include maintaining joint ROM and strength, improving cardiovascular fitness, and taking short rest periods during the day. Every individual with RA should implement joint protection and energy conservation programs into their lifestyle.
Medical Issues/Complications
The course for rheumatoid arthritis (RA) is variable. Some patients experience only months of discomfort while others endure progressive and disabling arthritis for decades. Approximately 10-15% of patients experience remission, a larger percentage of patients follow an indolent course, and the remaining patients demonstrate a severe, progressive course. The familiar scenario is one in which the patient begins to experience a gradual onset of symptoms such as malaise and fatigue, often accompanied by diffuse musculoskeletal pain (usually involving small joints), Raynaud phenomenon, and paresthesias. Later, development of specific pain, tenderness, swelling, and redness is noted in a symmetrical pattern. The disease is frequently polyarticular in nature, involving the hands, wrists, elbows, and shoulders. Areas that usually are spared include the DIP joints and the thoracolumbar spine.
Stiffness is noted following inactivity (gelling of the affected joints); this is the hallmark of the disease. Periarticular edema may be noted. As RA progresses, pain and stiffness worsen and gross permanent deformities develop, including bone subluxation, displacement, and fusion. All of these deformities may limit the patient's functional abilities. This is compounded by depression,6 weight loss, low-grade fever, and extra-articular findings such as rheumatoid nodules, tenosynovitis, weakening of capsules and ligaments, and tendon rupture.
Surgical Intervention
Surgical intervention in patients with rheumatoid arthritis (RA) includes pain relief, deformity correction, and functional improvement.5 A number of surgical procedures are available to obtain these goals. These options include myofascial techniques, excisions, reconstructions, joint fusions, and joint replacements. The timing of surgery is a complex decision; the patient's age, stage of disease, and level of disability, as well as the location of the involved joints, must be considered. Early surgical intervention may be helpful in maintaining a patient's functional level of independence.
Consultations
- Rheumatologist
- Orthopedist
- Infectious disease specialist
Medication
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Nonsteroidal anti-inflammatory agents
First-line agents in the treatment of rheumatoid arthritis. Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclo-oxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions. Choice of NSAIDs is individualized and usually is based on factors such as adverse effects profiles (eg, GI, renal, hepatic, CNS toxicities), polypharmacy (drug-drug interactions), and comorbidities.
Aspirin is inexpensive, but it can cause GI complications. Aspirin can be administered in an enteric coated preparation or in nonacetylated compounds. Concomitant gastroprotective agents may be used such as misoprostol, Carafate, H2 blockers, or omeprazole. Monitoring electrolytes, creatinine, Hgb, and LFTs every 4-6 months is important.
Nabumetone (Relafen)
Nonacidic NSAID rapidly metabolized after absorption to a major active metabolite that inhibits cyclo-oxygenase enzyme, which in turn inhibits pain and inflammation.
Adult
1 g/d PO in 1-2 divided doses; not to exceed 2 g/d
Pediatric
Not established
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; active peptic ulceration, hepatic impairment; third trimester of pregnancy
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Elderly patients may require lower doses; caution in hepatic and renal impairment
Aspirin (Ecotrin, Ascriptin, Anacin)
Treats mild to moderate pain. Inhibits prostaglandin synthesis, which in turn may inhibit pain and inflammation.
Adult
4 g/d PO in divided doses (take with fluids)
Pediatric
Individualize dosing; suggested dosing is 10-15 mg/kg/dose PO q4-6h; not to exceed 60-80 mg/kg/d
PABA may increase serum levels; may potentiate effects of anticoagulants, hypoglycemics, and methotrexate; effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses > 2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs
Documented hypersensitivity; liver damage, hypoprothrombinemia, vitamin K deficiency, bleeding disorders, and asthma; due to association of aspirin with Reye syndrome, do not administer in children younger than 16 years with flu; third trimester of pregnancy
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or who are taking anticoagulants; adverse reactions include gastric upset, prolonged bleeding time, asthma, rhinitis, urticaria, anaphylaxis, and salicylism
Celecoxib (Celebrex)
Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced by pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited, thus GI toxicity may be decreased. Seek lowest dose of celecoxib for each patient.
Adult
200 mg/d PO qd; alternatively, 100 mg PO bid
Pediatric
Not established
Coadministration with fluconazole may cause increase in celecoxib plasma concentrations because of inhibition of celecoxib metabolism; coadministration of celecoxib with rifampin may decrease celecoxib plasma concentrations
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause fluid retention and peripheral edema; caution in compromised cardiac function, hypertension, and conditions predisposing to fluid retention; caution in severe heart failure and hyponatremia because may deteriorate circulatory hemodynamics; NSAIDs may mask usual signs of infection; caution in the presence of existing controlled infections; evaluate therapy when symptoms or laboratory results suggest liver dysfunction
Ibuprofen (Motrin, Ibuprin, Excedrin IB, Advil)
DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Adult
400 mg PO q4-6h, 600 mg PO q6h, or 800 mg PO q8h while symptoms persist; not to exceed 3.2 g/d
Pediatric
20-70 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate; not to exceed 2.4 g/d
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, or high risk of bleeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy
Gold compounds
Second-line therapy for rheumatoid arthritis. Up to two thirds of patients get some benefit initially, but the long-term effect is unsatisfactory given a high profile of adverse effects (eg, dermatitis, stomatitis, proteinuria, cytopenia).
For patients who fail to improve on or who cannot tolerate methotrexate, treatment with gold salts may be effective. About 60% of patients may be expected to benefit from gold therapy, though complete remissions are uncommon. The mode of action of gold compounds is not known.
Auranofin (Ridaura)
Gold is taken by macrophages, which in turn inhibit phagocytosis and lysosomal membrane stabilization. Alters immunoglobulins, decreasing prostaglandin synthesis, and lysosomal enzyme activity.
Adult
6 mg PO qd in 1-2 divided doses initially; if response is inadequate after 6 mo, may increase to 3 mg tid; if still ineffective after 3 mo, discontinue treatment
Pediatric
Not established
Penicillamine, hydroxychloroquine, and antimalarials may increase toxicity of auranofin
Documented hypersensitivity; history of gold-induced disorders; renal impairment; history of blood dyscrasias, exfoliative dermatitis, congestive heart failure, or necrotizing enterocolitis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Discontinue therapy if platelet count falls <100,000/mm3, if WBC count is <4000, or if granulocyte count is <1500/mm3; adverse reactions include bone marrow depression, proteinuria, hematuria, diarrhea, GI upset, ulcerative colitis, rash, pruritus, peripheral neuropathy, proteinuria, nephrotic syndrome, and stomatitis (discontinue immediately if thrombocytopenia, proteinuria, or hematuria develop); be familiar with chrysotherapy and this product's toxicity before use; caution in history of bone marrow depression
Immunosuppressant agents
Second-line agents for rheumatoid arthritis (RA). Inhibit key steps in the development of immune reactions.5 Methotrexate is commonly used. Other cytotoxic agents, such as cyclophosphamide, also have been used in combination with other agents in the treatment of RA, especially in severe cases. However, due to the severity of toxic effects of cyclophosphamide (eg, hemorrhagic cystitis, infections, malignancy), investigators have not recommended combination chemotherapies that include cyclophosphamide.
Methotrexate (Rheumatrex)
Unknown mechanism of action in treatment of inflammatory reactions. May affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness).
Adult
7.5 mg PO qwk as single dose, or a course of three 2.5-mg doses at 12-h intervals qwk; not to exceed 20 mg/wk; adjust dose gradually to attain satisfactory response
Pediatric
Not established
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate (MTX); charcoal lowers MTX levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX; probenecid, NSAIDs, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, can increase MTX plasma levels; may decrease phenytoin plasma levels; may increase plasma levels of thiopurines
Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor CBC counts monthly and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels exists, eg, dehydration); MTX has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood counts occur; fatal reactions reported when administered concurrently with NSAIDs (be familiar with this drug's toxicity before use); obtain baseline and monitor CBC count with differentials, platelets, chest radiographs, as well as hepatic, renal, and pulmonary function; during therapy, monitor hematology monthly and renal and hepatic function every 1-2 mo, more often if increasing dose or predisposed to toxicity; discontinue immediately if blood counts drop significantly; rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle following treatment in women and for at least 3 months following treatment inmen; interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur
Antimalarial agents
Second-line agents in rheumatoid arthritis therapy. These drugs may impair immune reactions. They take several weeks to show clinical improvements.
Hydroxychloroquine (Plaquenil)
Inhibits chemotaxis of eosinophils, inhibits locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulfate (200 mg) is equivalent to 155-mg hydroxychloroquine base and 250-mg chloroquine phosphate.
Adult
400-600 mg PO qd with food or milk
Pediatric
Not established
Serum levels increase with cimetidine; magnesium trisilicate may decrease absorption
Documented hypersensitivity; psoriasis; retinal and visual field changes attributable to 4-aminoquinolines
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; not recommended for long-term use in children; visual symptoms or muscular weakness may occur; perform periodic (q6mo) ophthalmologic examinations; test periodically for muscle weakness
Anti-inflammatory agents
Second-line agents for rheumatoid arthritis. May inhibit key steps of immune reactions.
Sulfasalazine (Azulfidine)
Decreases inflammatory reactions and systemically inhibits prostaglandin synthesis.
Adult
500 mg PO bid initially; increase at weekly intervals to maximum 2-3 g qd in divided doses
Pediatric
Not established
Decreases effects of iron, digoxin, and folic acid; conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and methotrexate
Documented hypersensitivity; GI or GU obstruction
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients with renal or hepatic impairment, blood dyscrasias, or urinary obstruction
Corticosteroids
Second-line agents for the treatment of rheumatoid arthritis. Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Betamethasone (Celestone)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
2.4-4.8 mg/d PO bid/qid; range 0.6-7.2 mg/d PO
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; dexamethasone decreases effect of salicylates and vaccines used for immunization
Documented hypersensitivity; systemic fungal infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications of glucocorticoid use
Disease-modifying agents
Penicillamine is available for patients with severe rheumatoid arthritis. It interferes with key steps responsible for immune reactions.
Penicillamine (Cuprimine, Depen)
Depresses circulating IgM rheumatoid factor and T-cell activity but does not affect B-cell activity.
Adult
125-250 mg/d PO initially; may increase dose at intervals of 1-3 mo; not to exceed 1-1.5 g/d
Pediatric
3 mg/kg/d PO for 3 mo, then 6 mg/kg/d divided bid for 3 mo; not to exceed 10 mg/kg/d divided tid/qid
Increases effects of immunosuppressants, phenylbutazone, and antimalarials; decreases digoxin effects; effects may decrease with coadministration of zinc salts, antacids, and iron
Documented hypersensitivity; renal insufficiency; previous penicillamine-related aplastic anemia
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Thrombocytopenia, agranulocytosis, and aplastic anemia may occur
Adalimumab (Humira)
Recombinant human IgG1 monoclonal antibody specific for human TNF. Indicated to reduce inflammation and inhibit progression of structural damage in moderate-to-severe rheumatoid arthritis. Reserved for those who experience inadequate response to 1 or more DMARDs. It can be used alone or in combination with MTX or other DMARDs. Binds specifically to TNF-alpha and blocks interaction with p55 and p75 cell-surface TNF receptors.
Adult
40 mg SC q2wk; may increase to 40 mg SC qwk in some patients not taking concomitant MTX
Pediatric
Not established
May interfere with immune response to live virus vaccine (MMR) and reduce efficacy; MTX decreases clearance (available data do not support adjusting dose of either Humira or MTX)
Documented hypersensitivity; active infection
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Causes immunosuppression; may reactivate tuberculosis infection; increases risk for lymphoma development; associated with CNS demyelination (rare); discontinue if serious infection develops; autoantibody development may occur, causing lupuslike syndrome
Immunomodulators
Interfere with cytokine actions responsible for inflammation.
Abatacept (Orencia)
Selective co-stimulation modulator that inhibits T-cell activation by binding to CD80 and CED86, thereby blocking CD28 interaction. CD28 interaction provides a signal needed for full T-cell activation that is implicated in RA pathogenesis. Indicated for reducing signs and symptoms of RA, slowing progression of structural damage and improving physical function in adults with moderate-to-severe RA who have inadequate response to DMARDs, methotrexate, or TNF antagonists. May be used as monotherapy or with DMARDs (other than TNF antagonists, because of increased risk of serious infections [4.4% vs 0.8%]). Not recommended for concomitant use with anakinra (insufficient experience).
Adult
Dose according to body weight; after initial administration, repeat at 2 and 4 wk after first infusion, then q4wk; infuse over 30 min
<60 kg: 500 mg IV
60-100 kg: 750 mg IV
>100 kg: 1 g IV
Pediatric
Not established
In clinical trials, coadministration with TNF antagonists resulted in increased risk of serious infections; do not administer concurrently with live virus vaccines (eg, MMR) or within 3 mo of discontinuation
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Discontinue if serious infection occurs; patients with COPD developed adverse effects more frequently, including COPD exacerbations, cough, rhonchi, and dyspnea; serious adverse reactions include serious infections (3% vs 1.9% placebo); malignancy frequency was similar to that of placebo (1.3% vs 1.1% placebo), with the exception of lung cancer (0.2% vs 0% placebo); common adverse effects include headache, upper respiratory tract infection, nasopharyngitis, and nausea
More on Rheumatoid Arthritis |
| Overview: Rheumatoid Arthritis |
| Differential Diagnoses & Workup: Rheumatoid Arthritis |
 Treatment & Medication: Rheumatoid Arthritis |
| Follow-up: Rheumatoid Arthritis |
| Multimedia: Rheumatoid Arthritis |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
Allaire S, Wolfe F, Niu J, et al. Current risk factors for work disability associated with rheumatoid arthritis: recent data from a US national cohort. Arthritis Rheum. Mar 15 2009;61(3):321-8. [Medline].
Areskoug-Josefsson K, Oberg U. A literature review of the sexual health of women with rheumatoid arthritis. Musculoskeletal Care. Feb 25 2009;[Medline].
Ahlmen M, Svensson B, Albertsson K, et al. Influence of gender on assessments of disease activity and function in early rheumatoid arthritis in relation to radiographic joint damage. Ann Rheum Dis. Jan 21 2009;[Medline].
Jorgensen KT, Pedersen BV, Jacobsen S, et al. National cohort study of reproductive risk factors for rheumatoid arthritis in Denmark - a role for hyperemesis, gestational hypertension, and pre-eclampsia?. Ann Rheum Dis. Mar 15 2009;[Medline].
Luqmani R, Hennell S, Estrach C, et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of rheumatoid arthritis (after the first 2 years). Rheumatology (Oxford). Jan 27 2009;[Medline]. [Full Text].
Goldenberg DL. The interface of pain and mood disturbances in the rheumatic diseases. Semin Arthritis Rheum. Feb 12 2009;[Medline].
Barry MA, Purser J, Hazleman R, et al. Effect of energy conservation and joint protection education in rheumatoid arthritis. Br J Rheumatol. Dec 1994;33(12):1171-4. [Medline].
Guccione AA. Physical therapy for musculoskeletal syndromes. Rheum Dis Clin North Am. Aug 1996;22(3):551-62. [Medline].
Jain R, Lipsky PE. Treatment of rheumatoid arthritis. Med Clin North Am. Jan 1997;81(1):57-84. [Medline].
Klippel JH, ed. Primer on the Rheumatic Diseases. 13th ed. New York, NY: Springer; 2008.
Lipsky PE. Rheumatoid arthritis. In: Isselbacher KJ, Braunwald E, Fauci AS, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill; 1994:1648-55.
Nicholas JJ. Physical modalities in rheumatological rehabilitation. Arch Phys Med Rehabil. Sep 1994;75(9):994-1001. [Medline].
Nicholas JJ. Rehabilitation of patients with rheumatic disorders. In: Braddom RL, ed. Physical Medicine and Rehabilitation. Philadelphia, Pa: Saunders; 1996:711-27.
Further Reading
Clinical guidelines:
Ottawa Panel evidence-based clinical practice guidelines for therapeutic exercises in the management of rheumatoid arthritis in adults.
Ottawa Panel - Independent Expert Panel. 2004 Oct. 39 pages. NGC:004019
Ottawa Panel evidence-based clinical practice guidelines for electrotherapy and thermotherapy interventions in the management of rheumatoid arthritis in adults.
Ottawa Panel - Independent Expert Panel. 2004 Nov. 28 pages. NGC:004020
Rituximab for the treatment of rheumatoid arthritis.
National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.]. 2007 Aug. 26 pages. NGC:005902
Abatacept for the treatment of rheumatoid arthritis.
National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.]. 2008 Apr. 29 pages. NGC:006483
Clinical trials:
RESTART C0168Z05 Rheumatoid Arthritis Study
Evaluation of EULAR-RAID Score in Rheumatoid Arthritis Patients (Rainbow)
PPAR-Gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease (RA PPAR)
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