AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of undetermined etiology involving primarily the synovial membranes and articular structures of multiple joints. The disease is often progressive and results in pain, stiffness, and swelling of joints. In late stages deformity and ankylosis develop.

Pathophysiology

The cause of RA is unknown. The diagnosis is based routinely on the persistence of arthritic symptoms over time. The application of classification systems based on qualifying symptom criteria or on decision-tree methodology also aids in establishing a diagnosis.

Factors associated with RA include the possibility of infectious triggers, genetic predisposition, and autoimmune response. CD4⁺ T cells stimulate the immune cascade leading to cytokine production such as tumor necrosis factor alpha (TNF-a) and interleukin-1.

The primary targets of inflammation are synovial membranes and articular structures. Other organs are affected as well. Inflammation, proliferation, and degeneration typify synovial membrane involvement. Joint deformities and disability result from the erosion and destruction of synovial membranes and articular surfaces.

The disease course may be short and limited or progressive and severe.

Frequency

United States

Prevalence is approximately 1% in the United States. The occurrence rate ranges from 0.5% to greater than 5% depending on ethnic variation.

International

Prevalence is similar to that in the United States.

Mortality/Morbidity

Mortality from RA is related primarily to the patient's overall deterioration in health, well-being, and functionality. Patients with RA become susceptible to infection and secondary organ dysfunction (eg, lung disease, kidney disease, GI hemorrhage).

Race

Rates for arthritis vary from approximately 5-6% in Asian/Pacific Islanders to 12% in African Americans and 16% in whites.

Sex

Female-to-male ratio is approximately 3:1.

Age

Age of onset is usually between 25 and 50 years. The disease can occur at any age but tends to peak in the fourth and fifth decades of life. The pediatric form of RA is juvenile rheumatoid arthritis (JRA), which is characterized by onset in children younger than 16 years and includes 3 categories of disease: polyarticular (ie, multiple joints affected), pauciarticular (ie, fewer than 4 joints affected), and systemic (ie, high fever, rash, organ involvement).

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• RA is usually a disease of insidious onset, although it can be abrupt. The diagnosis typically is made when 4 of 7 qualifying criteria established by the American Rheumatism Association are met. These qualifying criteria are as follows:
• • Morning stiffness lasting longer than 1 hour before improvement
  • Arthritis involving 3 or more joints
  • Arthritis of the hand, particularly involvement of the proximal interphalangeal (PIP) joints, metacarpophalangeal (MCP) joints, or wrist joints
  • Bilateral involvement of joint areas (ie, both wrists, symmetric PIP and MCP joints)
  • Positive serum rheumatoid factor (RF)
  • Rheumatoid nodules
  • Radiographic evidence of RA
• Other contributing history includes the following:
• • General malaise
  • Weakness
  • Fever of undetermined etiology
  • Weight loss
  • Myalgias
  • Tendonitis
  • Bursitis

Physical

• Joint involvement is typically polyarticular and symmetrical, usually sparing the distal interphalangeal (DIP) joints. Joint involvement and inflammation is evinced by the following:
• • Edema
  • Effusion
  • Warmth
  • Tenderness to palpation
  • Destruction (a late finding)
  • Subcutaneous rheumatoid nodules, swan-neck deformities, boutonniere deformities, ulnar deviation of fingers at MCP joints (late findings)
  • Bursitis
• Various inflammatory disorders of remote organ systems may be present and may contribute to the presenting problem. Organ systems that may be affected include the following:
• • Cardiac - Carditis, pericarditis
  • Pulmonary - Pleuritis, intrapulmonary nodules, interstitial fibrosis
  • Hepatic - Hepatitis
  • Ocular - Scleritis, episcleritis, dryness of the eyes
  • Vascular - Vasculitis
  • Skin - Subcutaneous nodules, ulcers
• RA is a diffuse systemic disease involving many areas of the body. The presenting complaint may be remote from a joint or may involve inflammatory symptoms at a joint.

Causes

• The cause of RA has not been elucidated. Several possible associations have been described.
• Associated factors may include the following:
• • Genetic predisposition
  • Female sex
  • Psychological stress
  • Immune response
  • Hormone interaction
  • Viral infection

DIFFERENTIALS

Section 4 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Amyloidosis
Polyarteritis nodosa
Viral arthritis (eg, rubella, hepatitis B, parvovirus)
Whipple disease
Scleroderma
Paraneoplastic syndromes
Multicentric reticulohistiocytosis
Osteoarthritis (erosive)

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Complete blood count (CBC) indicates the presence of anemia in approximately 80% of patients with RA. The anemia is normocytic and normochromic.
• Thrombocytosis may be present.
• Erythrocyte sedimentation rate (ESR) is elevated in approximately 90% of patients with RA. This test usually is not performed in the acute setting.
• Serum RF result is positive in approximately 70% of patients with RA. This test is not routinely performed in the ED.
• Antinuclear antibodies (ANA) are present in approximately 30% of patients with RA. This test is not routinely performed in the ED.

Imaging Studies

• Radiography
• • Joints: Typical findings occur later in the disease course and include bony erosions, cysts, osteopenia, joint space swelling, calcifications, narrowed joint space, deformities, separations, and fractures.
  • Cervical spine: RA can affect the cervical spine with inflammation and destruction of cartilage, bone, and ligaments. This most commonly occurs in the upper cervical spine. Laxity and destruction of ligaments can lead to significant instability with frank subluxation and cord damage.
• CT and/or MRI of joints and cervical spine
• • CT and/or MRI can delineate further the pathology described above.
  • MRI may be necessary to demonstrate cord compression.

Other Tests

• Joint fluid analysis of an inflamed joint
• • Joint fluid analysis usually reveals a WBC count of 2,000-50,000/mm³ and no crystals or bacteria.
  • This may not be the case if gout, pseudogout, or infection is present.

Procedures

• Joint space aspiration
• • Consider joint space aspiration when making the definitive diagnosis of RA or when ruling out coexistent infection or crystal arthritis in an acutely swollen joint.
  • Analyze fluid for Gram stain, cell count, culture, and overall appearance.
  • Glucose and protein analyses are of limited value.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Emergency Department Care

Many nonmedication therapies are available for RA, including exercise, diet, massage, counseling, stress reduction, physical therapy, and surgery. Medication-based therapies comprise several classes of drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatologic drugs (DMARDs, also known as slow-acting antirheumatic drugs or SAARDS), immunosuppressants, biologic response modifiers, and corticosteroids. Although ED presentations may be due to initial disease presentation, patients with RA more commonly present with exacerbations of known disease or manifestations in other organ systems or sequelae. The following represent possible presentations:

• Patients presenting with initial presentation of previously undiagnosed possible RA require symptomatic treatment with NSAID therapy and rapid referral for definitive diagnosis and institution of DMARD therapy. Delay of as little as 2-3 months in initiating joint sparing therapy results in significant irreversible joint damage measured radiographically at 5 years.
• In patients with known disease, increased pain, edema, and dysfunction are characteristics of rheumatoid flare (exacerbation). Flares may be local or systemic in nature. Laboratory evaluation may reveal elevation in acute phase reactants. Treatment consists of rest, NSAIDs, DMARDs, short courses of steroids (2-4 wk), and possibly intraarticular steroid injections. Pain relief is important and may necessitate short-term use of narcotic analgesics.
• Felty syndrome is a triad of RA, neutropenia, and splenomegaly. Patients with Felty syndrome are prone to serious bacterial infections that result in higher rates of morbidity and mortality than for other patients with RA. This requires prompt diagnosis and initiation of antibiotic therapy.
• Ruptured Baker cysts are often confused with deep vein thrombosis (DVT). Baker cysts often occur fairly early in the course of the disease, with pain, edema, and inflammation in the posterior knee and calf. The diagnosis is best made with ultrasonography. Treatment includes rest, elevation, needle puncture of the calf, knee joint aspiration, and referral.
• Carpal tunnel syndrome (median nerve compression neuropathy) is evinced by pain and/or paresthesias in the median nerve distribution of the hand, a positive Phalen and/or positive Tinel test, or positive electromyography. Therapy includes rest, temporary immobilization, NSAIDs, and surgery.
• Cervical spine instability may be observed in patients with established RA who have degeneration of the ligaments and bone in the C-spine area. Degeneration of the transverse ligament can lead to instability at the C1-C2 level. Minor trauma can lead to neurologic sequelae due to inherent instability. Exercise caution when evaluating patients with RA after minor falls, motor vehicle accidents (MVAs), or other injuries. Cervical spine injury may occur spontaneously.
• Keratoconjunctivitis sicca occurs in approximately 25% of patients with RA. Symptoms include ocular discharge, foreign body sensation, and dry eye. Episcleritis may progress to scleromalacia if untreated. Treatment includes referral to ophthalmology, artificial tears, systemic NSAIDs, topical NSAIDs, systemic steroids, and cyclophosphamide.
• Patients with an established diagnosis of RA who are being treated with DMARDS, particularly those treated with combination therapy including the biologic response modifying agents such as anti-TNF antibody therapy, may be at an increased risk for serious infections and malignancies.

Consultations

• Consultation is necessary for this chronic disease. New onset disease requires rapid diagnosis and therapy with DMARDS. Rheumatoid flares and other sequelae require close follow up. Patients always should be referred back to their primary care physician/rheumatologist promptly for continuation of care.
• Consultation with rheumatology, orthopedics, and/or infectious disease may be necessary if indicated by the presenting complaint.
• Involvement by cardiology, pulmonology, nephrology, and ophthalmology often is necessitated by secondary organ involvement in those areas.

MEDICATION

Section 7 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

The treatment of RA historically has been a stepwise, pyramid progression beginning with rest, salicylates, and NSAIDs and progressing to the use of disease-modifying medications. Current recommendations suggest that for all but minor disease, the use of DMARDs and biologic response modifiers or combination drug therapy earlier in the disease course is more effective. Destruction of synovial tissue and joints can occur early in the disease process, before patients classically have been considered for progression of therapy.

Effective medications include methotrexate, sulfasalazine, corticosteroids, hydroxychloroquine, gold injections, d-penicillamine, minocycline, azathioprine, cyclosporine, etanercept, leflunomide, infliximab, adalimumab, etanercept, abatacept, and anakinra. The primary goals of ED management should be relief of acute symptomatology, ruling out significant complications, and coordination of chronic therapy with the patient's primary care physician and rheumatologist.

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs have been the cornerstone of therapy for RA. NSAIDs reduce pain and inflammation and allow for improvements in mobility and function. Several NSAIDs exist, but no single agent is clearly superior to another. The cyclooxygenase-2 (COX-2) inhibitors may offer some increase in efficacy with fewer adverse GI effects. The use of NSAIDs alone as single agents in RA should be reserved for mild, well-controlled disease. COX-2 inhibitors may be more effective in controlling inflammation.

Drug Category: Cyclooxygenase-2 (COX-2) inhibitors

Although increased cost can be a negative factor, the incidence of costly and potentially fatal GI bleeds is possibly less with COX-2 inhibitors than with traditional NSAIDs. Ongoing analysis of cost avoidance of GI bleeds will further define the populations that will find COX-2 inhibitors the most beneficial.

Drug Category: Disease-modifying agents

These drugs most frequently are used in various combination therapy regimens. They include methotrexate, hydroxychloroquine, gold, d-penicillamine, sulfasalazine, cyclosporine A, minocycline, azathioprine, leflunomide, infliximab, and etanercept. Please note that in JRA, d-penicillamine, gold, and antimalarials have not been proven effective. Pediatric safety has not been established for some of the newer agents.

Drug Name	Leflunomide (Arava)
Description	An immune response-modifying agent that inhibits T-cell proliferation and reduces inflammation.
Adult Dose	100 mg PO qd for 3 d, initially, followed by a maintenance dose of 10-20 mg PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Cholestyramine and charcoal reduce effects; concomitant administration with rifampin increases toxicity
Pregnancy	X - Contraindicated in pregnancy
Precautions	Serious adverse reactions include hepatotoxicity and immunosuppression; other reactions include nausea, diarrhea, abdominal pain, rash, bronchitis, headache, hypertension, dizziness, and alopecia; caution if impaired liver or renal function or if immunodeficient

Drug Name	Azathioprine (Imuran)
Description	Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.
Adult Dose	1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg q4wk until response or dose reaches 2.5 mg/kg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT)
Interactions	Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Pregnancy	D - Unsafe in pregnancy
Precautions	Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level before therapy and follow liver, renal, and hematologic function; pancreatitis rarely associated

Drug Name	Sulfasalazine (Azulfidine EN-tabs)
Description	Decreases the inflammatory response and systemically inhibits prostaglandin synthesis.
Adult Dose	0.5-1g/d PO; increase qwk to maintenance dose of 2 g/d PO divided bid; increase to 3 g/d if response not satisfactory after 12 wk of treatment; not to exceed 3 g/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; sulfa drugs or any component and those diagnosed with GI or GU obstruction
Interactions	Decreases effects of iron, digoxin, and folic acid; conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and methotrexate
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in patients with renal or hepatic impairment, blood dyscrasias, or urinary obstruction

Drug Name	Infliximab (Remicade)
Description	Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-a and inhibits its binding to TNF-a receptor. Reduces infiltration of inflammatory cells and TNF-a production in inflamed areas. Used with methotrexate in patients who have had inadequate response to methotrexate monotherapy.
Adult Dose	3 mg/kg IV (in combination with methotrexate therapy); follow by additional 3 mg/kg at 2wk and 6 wk after first dose; repeat q8wk thereafter
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity to murine proteins or components of formulation; serious clinical infections
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	TNF alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections

Drug Name	Adalimumab (Humira)
Description	Recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (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 one or more disease-modifying antirheumatic drugs (DMARDs). 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 Dose	40 mg SC q2wk; may increase to 40 mg SC qwk in some patients not taking concomitant MTX
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; active infection
Interactions	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)
Pregnancy	B - Usually safe but benefits must outweigh the risks.
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

Drug Name	Etanercept (Enbrel)
Description	Acts by binding and inhibiting TNF, cytokine that contributes to inflammatory and immune response.
Adult Dose	25 mg SC twice/wk
Pediatric Dose	0.4 mg/kg SC; not to exceed 25 mg/dose
Contraindications	Documented hypersensitivity, sepsis, concurrent live vaccination
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in impaired renal function and asthma; discontinue administration if a serious infection develops; adverse effects may include injection site pain, localized erythema, rash, URI symptomatology, GI upset, nausea, vomiting, rhinitis, and cough

Drug Category: Immunomodulators

Interfere with cytokine actions responsible for inflammation.

Drug Category: Interleukin-1 receptor inhibitors

Block effects of interleukin-1, which, in turn, may reduce inflammation and pain.

Drug Category: Glucocorticoids

These agents, used alone or in conjunction with other medications, may reduce the symptomatology associated with RA. These drugs can be given at low doses daily for maintenance or in large doses pulsed over 3 days for a rheumatoid flare.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Deterrence/Prevention

• As the cause of RA is unknown, methods of preventing the disease have not been established.
• Many approaches have been suggested to prevent or minimize recurrences or flares. These include proper nutrition, relaxation, low-impact exercise, flexibility exercises, yoga, tai chi, counseling, meditation, hydrotherapy, and stress reduction.

Prognosis

• Prognosis in RA is extremely variable.
• Some evidence suggests that the onset of disease (rapid versus insidious) may predict the progression of disease. Patients with rapid onset of disease may show better remission than those with insidious onset.
• Prognosis is worse with large joint involvement.

Patient Education

• Patients with RA require a great deal of education regarding the need for lifestyle changes to prevent exacerbations, to preserve mobility and functionality, and for appropriate pain management. Specific education for the ED visit is focused on the exacerbation or focal problem for which the patient presents.
• For excellent patient education resources, visit eMedicine's Arthritis Center. Also, see eMedicine's patient education articles Rheumatoid Arthritis, Juvenile Rheumatoid Arthritis, and Understanding Rheumatoid Arthritis Medications.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Missed diagnosis of a septic joint may lead to litigation. The tendency to ascribe joint pain and edema to the underlying RA may predispose the physician to miss an active bacterial infection or inflammation secondary to gout or pseudogout. New-onset monoarticular arthritis or an unusual pattern of a joint flare in a patient with RA should encourage strong consideration for joint aspiration and evaluation.
• Missed diagnosis of Felty syndrome may lead to litigation because these patients are at risk for serious bacterial infection.
• Missed secondary organ involvement (eg, pericarditis, pleuritis, pleural effusion) may lead to litigation.
• Failure to suspect and evaluate adequately the cervical spine status in a patient with RA following a minor injury or with symptoms or signs of potential cord compression may lead to litigation. Presence of C-spine instability can lead to disastrous outcomes with minor trauma.
• Overaggressive long-term treatment with salicylates or NSAIDs may result in GI hemorrhage and loss of opportunity in early initiation of joint-sparing DMARD medications.
• Failure to arrange for close follow-up may complicate or delay joint-sparing DMARD therapy initiation for RA.
• Concomitant use of NSAIDs and methotrexate can lead to significant bone marrow suppression and pancytopenia.
• Failure to consider that many of the newer DMARD therapies are immunosuppressive in nature leading to a higher propensity and possibility of partially masked serious bacterial infections

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Arthritis, Rheumatoid. Rheumatoid nodules at the elbow. Photograph by David Effron MD, FACEP
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Media file 2:  Arthritis, Rheumatoid. Rheumatoid changes in the hand. Photograph by David Effron MD, FACEP.
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Media file 3:  Arthritis, Rheumatoid. Rheumatoid changes in the hand. Photograph by David Effron MD, FACEP.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Alarcon GS. Predictive factors in rheumatoid arthritis. Am J Med. Dec 29 1997;103(6A):19S-24S. [Medline].
• American College of Rheumatology. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum. Feb 2002;46(2):328-46. [Medline].
• Barth WF. Office evaluation of the patient with musculoskeletal complaints. Am J Med. Jan 27 1997;102(1A):3S-10S. [Medline].
• Bongartz T, Sutton AJ, Sweeting MJ. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. May 17 2006;295(19):2275-85. [Medline].
• Breedveld FC, Weisman MH, Kavanaugh AF. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previ. Arthritis Rheum. Jan 2006;54(1):26-37. [Medline].
• Brown JH, Deluca SA. The radiology of rheumatoid arthritis. Am Fam Physician. Oct 1995;52(5):1372-80. [Medline].
• Dinant HJ, Dijkmans BA. New therapeutic targets for rheumatoid arthritis. Pharm World Sci. Apr 1999;21(2):49-59. [Medline].
• Edwards JC, Szczepanski L, Szechinski J. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. Jun 17 2004;350(25):2572-81. [Medline].
• Emery P. Therapeutic approaches for early rheumatoid arthritis. How early? How aggressive?. Br J Rheumatol. Nov 1995;34 Suppl 2:87-90. [Medline].
• Emery P, Symmons DP. What is early rheumatoid arthritis?: definition and diagnosis. Baillieres Clin Rheumatol. Feb 1997;11(1):13-26. [Medline].
• Finckh A, Simard JF, Duryea J. The effectiveness of anti-tumor necrosis factor therapy in preventing progressive radiographic joint damage in rheumatoid arthritis: a population-based study. Arthritis Rheum. Jan 2006;54(1):54-9. [Medline].
• Fleischmann RM. Early diagnosis and treatment of rheumatoid arthritis for improved outcomes: focus on etanercept, a new biologic response modifier. Clin Ther. Sep 1999;21(9):1429-42; discussion 1427-8. [Medline].
• Furst DE. The rational use of methotrexate in rheumatoid arthritis and other rheumatic diseases. Br J Rheumatol. Nov 1997;36(11):1196-204. [Medline].
• Giannini EH, Cawkwell GD. Drug treatment in children with juvenile rheumatoid arthritis. Past, present, and future. Pediatr Clin North Am. 1995;42(5):1099-125. [Medline].
• Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. Nov 2005;52(11):3381-90. [Medline].
• Jain R, Lipsky PE. Treatment of rheumatoid arthritis. Med Clin North Am. Jan 1997;81(1):57-84. [Medline].
• Kainberger F, Trattnig S, Czerny C, et al. MRI in assessment of the systemic manifestations of rheumatological disease. Br J Rheumatol. Dec 1996;35 Suppl 3:40-4. [Medline].
• Lo V, Meadows SE, Saseen J. When should COX-2 selective NSAIDs be used for osteoarthritis and rheumatoid arthritis?. J Fam Pract. Mar 2006;55(3):260-2. [Medline].
• Machold KP, Eberl G, Leeb BF. Early arthritis therapy: rationale and current approach. J Rheumatol Suppl. Jul 1998;53:13-9. [Medline].
• Metzger AL, Morris RI. Appropriate laboratory testing in rheumatic diseases. Lippincotts Prim Care Pract. Jan-Feb 1998;2(1):52-65. [Medline].
• Moncur C, Williams HJ. Rheumatoid arthritis: status of drug therapies. Phys Ther. Jun 1995;75(6):511-25. [Medline].
• O''Dell JR, Paulsen G, Haire CE, et al. Treatment of early seropositive rheumatoid arthritis with minocycline: four-year followup of a double-blind, placebo-controlled trial. Arthritis Rheum. Aug 1999;42(8):1691-5. [Medline].
• O'Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med. Jun 17 2004;350(25):2591-602. [Medline].
• Olsen NJ, Stein CM. New drugs for rheumatoid arthritis. N Engl J Med. May 20 2004;350(21):2167-79. [Medline].
• Pincus T. Long-term outcomes in rheumatoid arthritis. Br J Rheumatol. Nov 1995;34 Suppl 2:59-73. [Medline].
• Saag KG. Low-dose corticosteroid therapy in rheumatoid arthritis: balancing the evidence. Am J Med. Dec 29 1997;103(6A):31S-39S. [Medline].
• Schiff M. Emerging treatments for rheumatoid arthritis. Am J Med. Jan 27 1997;102(1A):11S-15S. [Medline].
• Simon LS. Arthritis: new agents herald more effective symptom management. Geriatrics. Jun 1999;54(6):37-42; quiz 44. [Medline].
• Strand V. Recent advances in the treatment of rheumatoid arthritis. Clin Cornerstone. 1999;2(2):38-50. [Medline].
• Stucki G, Langenegger T. Management of rheumatoid arthritis. Curr Opin Rheumatol. May 1997;9(3):229-35. [Medline].
• Svensson B, Boonen A, Albertsson K. Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial. Arthritis Rheum. Nov 2005;52(11):3360-70. [Medline].
• Taylor PC, Steuer A, Gruber J. Ultrasonographic and radiographic results from a two-year controlled trial of immediate or one-year-delayed addition of infliximab to ongoing methotrexate therapy in patients with erosive early rheumatoid arthritis. Arthritis Rheum. Jan 2006;54(1):47-53. [Medline].
• Towheed TE, Hochberg MC. Acute monoarthritis: a practical approach to assessment and treatment. Am Fam Physician. Nov 15 1996;54(7):2239-43. [Medline].
• Wagner U, Kaltenhauser S, Sauer H, et al. HLA markers and prediction of clinical course and outcome in rheumatoid arthritis. Arthritis Rheum. Feb 1997;40(2):341-51. [Medline].
• Wassenberg S, Rau R, Steinfeld P. Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. Nov 2005;52(11):3371-80. [Medline].
• Weinblatt ME. Efficacy of methotrexate in rheumatoid arthritis. Br J Rheumatol. Nov 1995;34 Suppl 2:43-8. [Medline].
• Yelin E, Wanke LA. An assessment of the annual and long-term direct costs of rheumatoid arthritis: the impact of poor function and functional decline. Arthritis Rheum. Jun 1999;42(6):1209-18. [Medline].

Article Last Updated: Jul 13, 2006