Contributor Information. Author
Katherine K Temprano, MD Assistant Professor of Internal Medicine, Division of Rheumatology, St Louis University School of Medicine
Katherine K Temprano, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American College of Rheumatology
Rheumatoid Arthritis

Practice Essentials
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown cause. An external trigger (eg, cigarette smoking, infection, or trauma) that triggers an autoimmune reaction, leading to synovial hypertrophy and chronic joint inflammation along with the potential for extra-articular manifestations, is theorized to occur in genetically susceptible individuals.

Essential update: Rituximab may be a better choice following failed TNF-inhibitor therapy. In a prospective, global, multicenter, open-label, observational study, Emery and colleagues found that RA patients with an inadequate response to treatment with a single TNF inhibitor have better outcomes if they are switched to rituximab rather than to an alternative TNF inhibitor. Patients were enrolled within 4 weeks of switching from an initial TNF inhibitor to either rituximab or an alternative TNF inhibitor.[1, 2]. Among the 405 patients switched to rituximab and 323 patients switched to an alternative TNF inhibitor, mean change in Disease Activity Score in 28 joints excluding patient’s global health component (DAS28-3)–erythrocyte sedimentation rate at 6 months was ?1.5 in the rituximab group and ?1.1 in the alternate TNF inhibitor group (P = .007). This difference was significant among patients who discontinued their initial TNF inhibitor because of inefficacy, but not among those patients who discontinued because of intolerance.[1, 2]

Signs and symptoms
In most patients with RA, onset is insidious, often beginning with fever, malaise, arthralgias, and weakness before progressing to joint inflammation and swelling.

Signs and symptoms of rheumatoid arthritis may include the following:

Persistent symmetric polyarthritis (synovitis) of hands and feet (hallmark feature)
Progressive articular deterioration
Extra-articular involvement
Difficulty performing activities of daily living (ADLs)
Constitutional symptoms
The physical examination should address the following:

Upper extremities (metacarpophalangeal joints, wrists, elbows, shoulders)
Lower extremities (ankles, feet, knees, hips)
Cervical spine
During the physical examination, it is important to assess the following:

Stiffness
Tenderness
Pain on motion
Swelling
Deformity
Limitation of motion
Extra-articular manifestations
Rheumatoid nodules

Guidelines for evaluation
Forthcoming updated European League Against Rheumatism (EULAR) management guidelines[3, 4]
2010 American College of Rheumatology (ACR)/EULAR classification criteria[5]
2012 ACR disease activity measures[6]
2011 ACR/EULAR definitions of remission[7]
See Clinical Presentation for more detail.

Diagnosis
No test results are pathognomonic; instead, the diagnosis is made by using a combination of clinical, laboratory, and imaging features. Potentially useful laboratory studies in suspected RA include the following:

Erythrocyte sedimentation rate
C-reactive protein level
Complete blood count
Rheumatoid factor assay
Antinuclear antibody assay
Anti?cyclic citrullinated peptide and anti?mutated citrullinated vimentin assays
Potentially useful imaging modalities include the following:

Radiography (first choice): Hands, wrists, knees, feet, elbows, shoulders, hips, cervical spine, and other joints as indicated
Magnetic resonance imaging: Primarily cervical spine
Ultrasonography of joints: Joints, as well as tendon sheaths, changes and degree of vascularization of the synovial membrane, and even erosions
Joint aspiration and analysis of synovial fluid may be considered, including the following:

Gram stain
Cell count
Culture
Assessment of overall appearance
See Workup for more detail.

Management
Nonpharmacologic, nonsurgical therapies include the following:

Heat and cold therapies
Orthotics and splints
Therapeutic exercise
Occupational therapy
Adaptive equipment
Joint-protection education
Energy-conservation education.

Guidelines for pharmacologic therapy
Forthcoming updated European League Against Rheumatism (EULAR) management guidelines[3, 4]
2012 updates to 2008 ACR recommendations for use of nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs)
2007 Agency for Healthcare Research and Quality (AHRQ) recommendations
Nonbiologic DMARDS include the following:

Hydroxychloroquine
Azathioprine
Sulfasalazine
Methotrexate
Leflunomide
Cyclosporine
Gold salts
D-penicillamine
Minocycline
Biologic TNF-inhibiting DMARDs include the following:

Etanercept
Infliximab
Adalimumab
Certolizumab
Golimumab
Biologic non-TNF DMARDs include the following:

Rituximab
Anakinra
Abatacept
Tocilizumab
Tofacitinib
Other drugs used therapeutically include the following:

Corticosteroids
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Analgesics
Surgical treatments include the following:

Synovectomy
Tenosynovectomy
Tendon realignment
Reconstructive surgery or arthroplasty
Arthrodesis
See Treatment and Medication for more detail.