AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

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

INTRODUCTION

Section 2 of 9  

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

Background

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease characterized by synovitis and serositis (inflammation of the lining surfaces of the joints, pericardium, and pleura), rheumatoid nodules, and vasculitis. The hallmark feature of the disease is persistent symmetric polyarthritis (synovitis) that affects the hands and feet, although any joint lined by a synovial membrane may be involved. In addition to articular deterioration, systemic involvement may lead to weight loss, low-grade fever, and malaise. The severity of RA may fluctuate over time, but chronic RA most commonly results in the progressive development of various degrees of joint destruction, deformity, and a significant decline in functional status.

Juvenile rheumatoid arthritis (JRA) is the most common form of childhood arthritis. The cause remains unknown. For most patients, the immunogenic associations, clinical pattern, and functional outcome are different from adult onset RA.

The diagnostic criteria for JRA are onset occurring when younger than 16 years, persistent arthritis in one or more joints for at least 6 weeks, and exclusion of other types of childhood arthritis. The key points that characterize the diagnosis of JRA are as follows:

• Arthritis must be present. Arthritis is defined as the presence of swelling, the presence of effusion, or the presence of 2 or more of the following signs: limited range of motion (ROM), tenderness, pain on motion, or joint warmth.
• Arthritis must persist for at least 6 weeks.
• Other causes of chronic arthritis in children must be ruled out.
• No specific laboratory or other test can establish the diagnosis of JRA.

Pathophysiology

The diagnosis of RA must be considered in any patient with polyarticular inflammatory arthritis, especially if both the hands and feet are involved. The early phase of the disease is characterized by the following features:

• Joint swelling that may affect joint margins
• Joint tenderness upon palpation
• Systemic malaise
• Loss of energy
• Severe morning stiffness that limits function and generally lasts more than an hour

A classic feature of the illness is the symmetry of involvement. If synovial-based inflammation persists over time, permanent damage to tendons, ligaments, and cartilage and subchondral bone destruction occur with resultant joint deformity and limited motion. Inflammation and deformity also are nearly always seen in the hands and feet. However, involvement of the knees, hips, and shoulders accounts for significant morbidity that leads to work disability in a large percentage of patients.

A major difference in the pathophysiology of RA versus osteoarthritis or mechanical joint problems is the presence of extensive synovial inflammation. The characteristic signs of inflammation were stated by Celsus as "rubor et tumor cum calore et dolore," meaning redness and swelling with heat and pain. Galen later added "et functio laesa" (disturbed function) to the characteristic signs of inflammation. Joint tenderness, swelling, stiffness, and pain on motion are the features of inflammation experienced by patients with RA.

Frequency

United States

The prevalence rate of RA is approximately 1% of the population (range 0.3-2.1%).

Race

RA is observed throughout the world and affects persons of all races.

Sex

Women are affected approximately 3 times more often than men. Sex differences diminish in older age groups.

Age

Although RA can occur at any age, the incidence increases with advancing age. The peak incidence of RA occurs in individuals aged 40-60 years.

CLINICAL

Section 3 of 9  

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

History

Stiffness of the joints is a major symptom in any type of arthritis and particularly in RA. Frequently, RA is accompanied by "morning stiffness." Other inflammatory conditions, such as polymyalgia rheumatica and ankylosing spondylitis, also may be accompanied by morning stiffness. The severity of stiffness may better differentiate a primary inflammatory process from other joint processes. Edema of the synovium and periarticular structures contributes to stiffness in RA by mechanically interfering with the usual biomechanics of the joint. With normal sleep patterns, stiffness is most pronounced in the morning, in part due to redistribution of interstitial fluid while sleeping.

Pain is a significant problem for most patients with RA. Although the assessment is subjective, the patient's relief from pain is the objective for treatment. Swollen joints with an applied load or joints with rapidly evolving effusions may be extremely painful due to high intra-articular pressures that lead to excessive stresses on the extensively innervated periarticular supporting structures.

Physical

Effects of rheumatoid arthritis on particular joints

Fingers

The boutonniere deformity describes nonreducible flexion at the proximal interphalangeal (PIP) joint along with hyperextension of the distal interphalangeal (DIP) joint of the finger. This deformity occurs as a result of synovitis stretching or rupturing of the PIP joint through the central extensor tendon with concomitant volar displacement of the lateral bands. When the lateral bands have subluxed far enough to pass the transverse axis of the joint, they become flexors of the PIP joint. Hyperextension of the DIP joint occurs as the tendons shorten with time. A compensatory and reducible hyperextension may occur at the metacarpophalangeal (MCP) joint. Consequences of boutonniere deformity are loss of thumb mobility and pincher grasp.

Swan-neck deformity of the finger describes hyperextension at the PIP joint with flexion of the DIP joint. The deformity may be initiated by (1) disruption of the extensor tendon at the DIP joint with secondary shortening of the central extensor tendon and hyperextension of the PIP joint or (2) volar herniation of the PIP joint capsule due to weakening from chronic synovitis with subsequent tightening of the lateral bands and central extensor tendon. The lateral bands may become shortened over time and lie dorsally, limiting PIP flexion and ineffectively extending the DIP joint.

Tightness of intrinsic muscles (eg, interossei, lumbricals) may cause major declines in mobility of the fingers. This characteristic is ascertained on examination when the PIP joint cannot be flexed while the MCP joint is fully extended, but it can be flexed if the MCP is in flexion (Bunnell test); primary PIP joint pathology would be evident with the MCP joint in either position. To assess this accurately, the phalanx must be aligned with the metacarpal since the intrinsics on the ulnar side are slack when ulnar deviation at the MCP joint exists, thus allowing more motion.

Flexor tenosynovitis of the fingers is common and suggests a poor prognosis. Tenosynovitis is defined as inflammation of the tendon and its enveloping tendon sheath. "Triggering" of the finger occurs when thickening or nodule formation of the tendon interacts with the concomitant tenosynovial proliferation, trapping the tendon in a flexed position (stenosing tenosynovitis). Tendon rupture may occur due to infiltrative synovitis in the digit or bony erosion of the tendon at the wrist (especially the flexor pollicis longus).

Arthritis mutilans (ie, opera glass hands) results if destruction is severe and extensive, with dissolution of bone. In the small joints of the hands, the phalanges may shorten and the joints may become grossly unstable. Pulling on the fingers during examination may lengthen the digit much like opening opera glasses, or the joint may bend in unusual directions merely under the pull of gravity.

Metacarpophalangeal joints

Two typical deformities that alter the alignment of the palmar skeletal arches and the stability of the fingers may occur at the MCP joints: volar subluxation and ulnar deviation. Most cases of ulnar deviation are accompanied by counterpoised radial deviation of the wrist, roughly proportional to the degree of ulnar deviation of the fingers. The volar plate is firmer and more substantial than other portions of the MCP joint capsule and, therefore, effectively limits extension and dorsal movement at the joint. The greater relative strength of the flexor muscles as compared to the extensor muscles causes volar migration of the proximal phalanx after synovial-based inflammation has weakened ligament and tendon insertions about the MCP joint capsule.

Ulnar deviation occurs after synovitis has led to stretching and attenuation of the volar plate and collateral ligaments, allowing dislocation of the flexor tendon volarward and ulnarward. The supporting structures of the extensor tendons also may become attenuated or destroyed by synovial distension and invasion, loosening the tendons so that they no longer ride centrally and dorsally over the metacarpal head but move into the cleft between the MCP joints. If the extensor tendon subluxation is beyond the transverse axis of the MCP joint, the tendon becomes a flexor at that joint, further limiting the active extension of the fingers.

Wrists

Multiple deformities may occur in the wrist. Disruption of the radioulnar joint with dorsal subluxation of the ulna (caput ulna) as well as rotation of the carpus on the distal radius with an ulnarly translocated lunate are common. The combination of an ulnar drift of the fingers and carpal rotation is known as a "zig-zag" deformity. Shortening of the carpal height (noted on radiographs), due in part to cartilage loss, is seen with rotational deformities.

Dorsal subluxation of the ulna often allows the ulnar styloid to be depressed volarly on examination, much like depressing a piano key. Subluxation may lead to rupture of the extensor tendons of the little, ring, and long fingers as the end of the distal ulna is roughened secondary to erosion of bone and may abrade the tendons as they move back and forth during normal hand function, much like a rope being frayed while rubbing over a sharp rock. This process is especially likely to lead to tendon rupture if there is associated tenosynovitis.

Entrapment neuropathy may result from synovitis about the flexor tendons. Entrapment of the median nerve as it passes through the carpal tunnel leads to decreased sensation on the palmar aspect of the thumb, index, and long fingers and on the radial aspect of the ring fingers; weakness and atrophy of the muscles in the thenar eminence also occurs. The less frequent entrapment of the ulnar nerve at the wrist causes decreased sensation over the little finger and the ulnar aspect of the ring finger and decreased interosseous muscle strength and mass.

Elbow

Elbow involvement often is detected by palpable synovial proliferation at the radiohumeral joint and commonly is accompanied by a flexion deformity, such as in contractures. Olecranon bursal involvement is common, as are rheumatoid nodules in the bursa and along the extensor surface of the ulna.

Shoulders

RA commonly involves the shoulders. RA in the shoulders is manifested by tenderness, nocturnal pain, and limited motion. Initially, swelling occurs anteriorly, but it may be difficult to detect and is present on examination in a minority of patients at any point in time. Rotator cuff degeneration secondary to synovitis may limit abduction and rotation. Superolateral migration of the humerus occurs with complete tears. Glenohumeral damage leads to pain both with motion and at rest and typically leads to severely restricted motion or "frozen shoulder syndrome." Acromioclavicular arthritis is not as frequent or as disabling.

Feet and ankles

The ankle joint itself is rarely involved without midfoot or MTP involvement. The ankle does not often deform, as it is a mortice joint. Major structural changes occur in the midfoot and foot due to the combination of chronic synovitis and weight bearing. Posterior tibialis tendon involvement or rupture may lead to subtalar subluxation, which results in eversion and migration of the talus laterally. Midfoot disease leads to loss of normal arch contour with flattening of the feet.

The MTP joints are inflamed in most patients and, due to the heavy loads they bear, commonly become deformed over time. The great toe typically develops hallux valgus (a bunion); subluxation of the phalanx at the MTP joint of the other toes predominantly occurs dorsally. The toes may exhibit compensatory flexion due to a fixed length of the flexor tendons, thus resulting in "hammer toes" (thought to look like piano hammers). The second and third metatarsal heads commonly protrude and may become the primary weight-bearing surface at the MTP joints. Calluses and pain upon weight bearing result.

Knees

Knees may develop large effusions and abundant accumulation of synovium. Knee effusions and synovial thickening are common and are easily detected during the early course of the disease. Persistent effusions may lead to inhibition of quadriceps function by spinal reflexes, resulting in subsequent atrophy. Instability may develop after progressive loss of cartilage and weakening of ligaments; deformity may include genu valgus or varus and flexion deformities. The energy expenditure to stand or walk significantly increases if there are flexion deformities of the knees.

Hips

The hip is commonly involved in RA; however, because of its deep location, its involvement is not always readily apparent early on during the course of the disease. Hips are difficult to examine by direct inspection or palpation. Limited motion or pain on motion and weight bearing are the hallmarks of hip involvement. The Patrick maneuver (flexion, external rotation, and abduction) is abnormal in this situation. A flexion deformity may be demonstrable by conducting a Thomas test. The Thomas test is performed by flexing one hip (with the patient supine) while restricting pelvic motion by keeping the other hip in the neutral position on the examination table. If the hip cannot be maintained in the neutral position, a contracture is present.

Cervical spine

Neck pain on motion and occipital headache are common manifestations of cervical spine involvement. Most patients with cervical spine involvement have a history of the disease for more than 10 years. Clinical manifestations of early cervical spine disease consist primarily of neck stiffness that is perceived throughout the entire arc of motion. The atlantoaxial joint is a synovial-lined joint and is susceptible to the same proliferative synovitis and subsequent instability seen in the peripheral joints. Patients with severe destruction in the hands (arthritis mutilans) are very likely to have symptomatic cervical spine abnormalities, as are those patients taking significant amounts of corticosteroids for control of RA.

Neurologic involvement ranges from radicular pain to a variety of spinal cord lesions that may result in weakness (including quadriparesis), sphincter dysfunction, sensory deficits, and pathologic reflexes. Transient ischemic attacks and cerebellar signs may reflect vertebral artery impingement from cervical subluxation or basilar artery impingement from upward migration of the dens. Tenosynovitis of the transverse ligament of C1 may lead to C1-C2 instability. Myelopathy secondary to rupture of the transverse ligament may lead to neurologic deficits. Radiculopathy is most common at the C2 root, though symptomatic subluxations may occur at any level.

Symptoms of cervical myelopathy are gradual in onset and are often unrelated to either the development of or accentuation in neck pain. When neck pain does occur, it frequently radiates over the occiput region in the distribution of the C1-3 nerve roots. The Lhermitte sign, in which tingling paresthesias that descends through the thoracolumbar spine occurs as the cervical spine is flexed, is typically observed.

During the physical examination, it is important to assess the following signs and symptoms:

• Stiffness
• • On physical examination, stiffness is determined by limitation of motion, which may vary with the time of day. Stiffness due to articular surface derangement or soft tissue contractures about the joint does not vary with the time of day.
  • Severe stiffness in the hands may improve with heat, but it is most effectively relieved with active exercise. These modalities reduce stiffness immediately after application, but unfortunately, they do not prevent the return of stiffness.
• Tenderness
• • Direct palpation can elicit joint tenderness.
  • Tenderness can vary significantly among patients and with the method of application of force used to elicit tenderness. The examiner should try to apply approximately the same pressure for each patient examined to minimize variation over time.
  • The enlarged synovial membrane, periarticular ligaments, and supporting structures are the major pain-sensitive structures.
  • Muscles also may become tender, but rarely is this due to myositis. Muscle tenderness is not specific for RA. Severe muscle tenderness should suggest other differential diagnoses including fibromyalgia or a regional pain disorder.
  • Bony prominences are generally tender, as periarticular structures tend to be more vulnerable to palpation at these sites.
• Pain on motion
• • Pain on motion often is used as a surrogate for tenderness in joints that are difficult to directly palpate due to overlying muscle and other tissues. The areas that are difficult to palpate include the cervical spine, shoulder, and hip.
  • Pain on motion of the joint may be due to noninflammatory processes that also interfere with the joint's normal, almost frictionless motion, including damage of cartilage and bone.
  • Additionally, joint instability or subluxation causes pain on motion because of musculotendinous imbalances across the joint. Documenting the positions of motion at which pain occurs can be useful.
• Swelling
• • Early in the disease process, there is an influx of inflammatory cells into the synovial membrane with subsequent angiogenesis, proliferation of chronic inflammatory (mononuclear) cells and resident synovial cells, and marked histologic changes—a 2-cell layer lining membrane changes to a thickened membrane often having villous projections into the joint space.
  • Enlargement of the synovial membrane is noted on physical examination as thickening of the synovium that may obscure joint margins. This thickening is most evident in the small joints of the hands and feet. In the MCP and metatarsophalangeal (MTP) joints, the outline of the base of the proximal phalanx may become indistinct, and in the PIP joints of the fingers, a fusiform swelling is noted due to the anatomy of the synovial reflections.
  • If synovial proliferation is abundant, a doughy texture may be felt due to the resultant soft tissue mass. Such synovial proliferation is commonly identified in the PIP, MCP, elbow, ankle, MTP, and knee joints, as well as in the flexor tendons of the fingers, the common extensor compartment of the dorsal wrist, and the extensor carpi ulnaris tendon sheath.
  • Joint effusions also may contribute to swelling by distending the joint. When the effusion is put under increased pressure with joint flexion, the synovium may be forced between articular structures and a portion becomes trapped and separated from the rest of the joint, forming a Baker cyst. More fluid is forced into the structure with subsequent loading of the distended joint, and a one-way valve effect may prevent the fluid from returning to the joint.
  • Baker cysts may be seen in most peripheral joints and are most commonly recognized in the knee. The larger the effusion, the more likely a painful cyst will develop. Rupture of a Baker cyst at the knee may resemble acute thrombophlebitis with distal dissection of inflammatory joint contents along fascial planes as far as the ankle and dorsal foot.
• Deformity
• • Deformity of the joint may develop over time as articular and supporting structures are damaged by the inflammatory process.
  • By the time deformity has developed, the diagnosis of RA is in little doubt; however, recognition of the inflammatory aspects of the arthritis before the development of deformity is required for optimal management of RA. Loss of cartilage from proteolytic and mechanical degradation, combined with stretching and weakening of the periarticular ligaments and their attachments, allows forces acting across the joints to deform them. The small joints in the hands and feet are most commonly deformed in this manner; greater than 10% of patients with RA develop deformity of the small joints of the hands within the first 2 years of the disease, and at least one third develop such deformities over time. Joint instability is seen if disruption of supporting structures has occurred.
• Limitation of motion
  • Limitation of motion occurs as a result of articular surface damage, joint and tendon sheath swelling, or alteration of joint supporting structures.
  • Effusion may limit joint motion through pain or by causing sufficient tightness of the joint capsule to impede joint mobility.
  • Fibrosis involving tendons and muscles may limit normal joint motion and result in flexion contractures.
  • Joint deformities and subluxations invariably limit motion because of mechanical factors.
• Extra-articular manifestations
  • RA is a systemic disease, and most individuals with the disease experience extra-articular manifestations such as generalized malaise and fatigue.
  • Rarely, a patient presents with extra-articular manifestations prior to the onset of arthritis. Some of these manifestations are more common in men (eg, pleural involvement, vasculitis, pericarditis), but the proportion of men and women involved with other manifestations is similar to that of RA overall.
• Rheumatoid nodules
  • Rheumatoid nodules occur in approximately 25% of patients with RA, but they occur in less than 10% of patients during the first year of the disease. They are most commonly found on extensor surfaces or sites of frequent mechanical irritation.
  • The olecranon process, proximal ulna, back of the heel, occiput, and ischial tuberosities are common periosteal sites for rheumatoid nodule development. Nodules also may form in subcutaneous tissues of the finger, in toe and heel pads, in tendons, and in viscera.
  • Rheumatoid factor (RF) is almost invariably present, and if absent, other diagnoses are suggested.
  • Frequently, there is a discrepancy between the level of articular inflammation and the progression of nodule formation. Patients with rheumatoid nodulosis have a great number of nodules, usually subcutaneous, and may have little active synovitis. In a similar fashion, patients whose articular inflammation responds well to treatment with methotrexate may have a seemingly paradoxical rapid increase in the number of nodules.

Causes

The cause of RA is still unclear, despite extensive studies of many variables such as endocrinic, metabolic, nutritional, geographic, occupational, and psychosocial factors—all of which influence disease manifestation but not frequency of the disease. Infectious etiologies have been implicated; however, specific inciting agents have not been identified. Data that suggest infectious etiologies include resemblance of RA to caprine arthritis-encephalitis caused by lente viruses, mycoplasmal arthritis in rodents, and Erysipelothrix infections in swine. Measles and parvovirus have been cultured from seronegative RA joints. Ongoing studies are investigating these implications.

DIFFERENTIALS

Section 4 of 9  

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

Other Problems to be Considered

The differentiation of RA from other diseases of connective tissue can be difficult; however, certain clinical features are helpful. Rheumatic fever is characterized by the migratory nature of the arthritis, an elevated antistreptolysin titer, and a more dramatic and prompt response to aspirin. Carditis and erythema marginatus may occur in adults, but chorea and subcutaneous nodules virtually never do. Butterfly rash, discoid lupus erythematosus, photosensitivity, alopecia, a high titer to anti-DNA, renal disease, and central nervous system abnormalities suggest the diagnosis of systemic lupus erythematosus (SLE).

Degenerative joint disease is not associated with constitutional manifestations; in contrast to the morning stiffness of RA, the joint pain with degenerative joint disease is characteristically relieved by rest. Signs of articular inflammation prominent in RA are usually minimal in degenerative joint disease. In contrast to RA, osteoarthritis spares the wrist and the MCP joints. While in the early years, gouty arthritis is almost always intermittent and monarticular, in later years it can become a chronic polyarticular process that mimics RA. Gouty tophi can at times resemble rheumatoid nodules. The early history of intermittent monarthritis and the presence of synovial urate crystals are distinctive features of gout.

Pyogenic arthritis can be distinguished by chills and fever, demonstration of the causative organism in joint fluid, and the frequent presence of a primary focus elsewhere (eg, gonococcal arthritis). Chronic Lyme disease typically involves only one joint, most commonly the knee, and is associated with positive serologic tests. Human parvovirus B19 infection in adults can occasionally mimic RA. Polymyalgia rheumatica occasionally causes polyarthritis in patients older than 50 years, but these patients remain to have a negative rheumatoid factor and have chiefly proximal muscle pain and stiffness.

A variety of cancers produce paraneoplastic syndromes, including polyarthritis. One form is hypertrophic pulmonary osteoarthropathy, which is most often produced by lung and gastrointestinal carcinomas. Hypertrophic pulmonary osteoarthropathy is characterized by a rheumatoidlike arthritis associated with clubbing, periosteal new bone formation, and a negative rheumatoid factor. Diffuse swelling of the hands with palmar fascitis also has been reported with a variety of cancers, especially ovarian carcinoma.

WORKUP

Section 5 of 9  

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

Lab Studies

• Serum protein abnormalities are often present. Rheumatoid factor (RF), an immunoglobulin M (IgM) antibody directed against the Fc fragment of immunoglobulin G (IgG), is present in the sera of more than 75% of patients. High titers of RF are commonly associated with severe rheumatoid disease. Antinuclear antibodies are demonstrable in 20% of patients, though their titers are lower in RA than in SLE. During both acute and chronic phases, erythrocyte sedimentation rate and the gamma globulins (commonly IgM and IgG) are usually elevated; however, leukopenia may occur in the presence of splenomegaly (Felty syndrome). The platelet count often is elevated, roughly in proportion to the severity of overall joint inflammation. Joint fluid examination is valuable, reflecting abnormalities that are correlated with varying degrees of inflammation.

Imaging Studies

• Plain radiographs
• • Radiography is the most specific workup study for RA.
  • Radiographs taken during the first 6 months typically are read as negative because of decreased sensitivity during that period.
  • The earliest changes occur in the wrists or feet and consist of soft tissue swelling and juxta-articular demineralization. Later, diagnostic changes of uniform joint-space narrowing are evident, and erosions develop. The erosions are often first evident at the ulnar styloid and at the juxta-articular margins, where the bony surface is not protected by cartilage.
  • Diagnostic changes also occur in the cervical spine with C1-2 subluxation, but these changes usually take several years to develop.
• Nuclear imaging studies
• • Nuclear imaging studies are quite sensitive for detecting many disease processes, and the entire body can be imaged at once. However, this technique is not specific because of the number of disease processes that may cause radionuclide accumulation.
  • When areas of increased uptake are observed, additional studies such as radiography are usually necessary to specify the type of abnormality.
  • Joints affected by inflammatory or degenerative arthritis demonstrate increased uptake and can map the extent of disease in a single examination.
  • In a patient with inflammatory arthritis and widespread changes on radiographs, scintigraphy may help locate areas of early active inflammation.

TREATMENT

Section 6 of 9  

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

Rehabilitation Program

Physical Therapy

The goals of rehabilitation for patients with 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.

Therapeutic modalities

Superficial or deep heat is an effective modality to relieve 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, ultrasound, diathermy, or paraffin. Both 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 muscular strength is noted. This reduction is due both 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 were noted in the joints of these patients. In addition, patients undergoing long-term endurance training felt less isolated, had less sick leave, and had 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 RA. 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 thumbpost 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 of how to prevent overuse of a joint and how to avoid biomechanical torques that excessively bend the joint. The use of adaptive equipment is important. In addition, other components of a good joint protection program include maintenance of good posture, avoiding 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 the decreased cardiovascular endurance observed in patients with this inflammatory disease.

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 the maintenance of joint ROM and strength, the improvement of 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 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 rest of 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 symmetric 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, 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 RA includes relief of pain, correction of deformities, and functional improvement. A number of surgical procedures are available to obtain these goals. These options include myofascial techniques, excisions, and reconstructions, as well as joint fusion and joint replacements. The timing of surgery is a complex decision; the patient's age, stage of disease, level of disability, and the location of the involved joints must be considered. Early surgical intervention may be helpful to maintain a patient's functional level of independence.

Consultations

• Rheumatologist
• Orthopedist
• Infectious disease specialist

MEDICATION

Section 7 of 9  

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

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Drug Category: Nonsteroidal anti-inflammatory agents

First-line agents. 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 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.

Drug Name	Aspirin (Ecotrin, Ascriptin, Anacin)
Description	Treats mild to moderate pain. Inhibits prostaglandin synthesis, which in turn may inhibit pain and inflammation.
Adult Dose	4 g/d PO in divided doses (take with fluids)
Pediatric Dose	Individualize dosing; suggested dosing is 10-15 mg/kg/dose PO q4-6h; not to exceed 60-80 mg/kg/d
Contraindications	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
Interactions	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
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	Pregnancy category D in third trimester; 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

Drug Name	Celecoxib (Celebrex)
Description	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 Dose	200 mg/d PO qd; alternatively, 100 mg PO bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	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
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	Category D in third trimester of pregnancy; 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

Drug Name	Ibuprofen (Motrin, Ibuprin, Excedrin IB, Advil)
Description	DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Adult Dose	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 Dose	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
Contraindications	Documented hypersensitivity; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, or high risk of bleeding
Interactions	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
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Category D in third trimester of pregnancy; caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy

Drug Category: Gold compounds

Second-line therapy. 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.

Drug Category: Immunosuppressant agents

Second-line agents. Inhibit key steps in the development of immune reactions. 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 chemotherapy, which includes cyclophosphamide.

Drug Category: Antimalarial agents

Second-line agents. May impair immune reactions. Takes several weeks to show clinical improvements.

Drug Category: Anti-inflammatory agents

Second-line agents. May inhibit key steps of immune reactions.

Drug Category: Corticosteroids

Second-line agents. Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Drug Category: Disease-modifying agents

Penicillamine is available for patients with severe RA. Interferes with key steps responsible for immune reactions.

Drug Name	Adalimumab (Humira)
Description	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 one 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 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 - 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

Drug Category: Immunomodulators

Interfere with cytokine actions responsible for inflammation.

FOLLOW-UP

Section 8 of 9  

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

Transfer

• Once a deformity has been detected, a cooperative multidisciplinary approach between the physician, therapist, and patient must be formed to eliminate the deformity or at least to prevent it from getting worse. Initially, outpatient management involves application of moist heat to the joints, followed by ROM active stretching exercises. This procedure helps reduce the contracture if the inflammation is relieved or is not too severe. If severe, protective splints should be applied. Most patients complain of fatigue, feel chronically tired, and usually do not want to exercise secondary to pain. When strength and endurance is compromised, a course of inpatient rehabilitative therapies may be warranted.

Deterrence

• RA can lead to a significant functional decline in patients. RA is the second leading cause of chronic disability in the United States. The physiatrist plays an active role in the management of the disease and has a variety of nonpharmacologic options available to help patients maintain their functional status.

Complications

• Medical complications
• • Skin manifestations
    • Rheumatoid nodules develop at some time in up to 50% of patients with RA.
    • Vasculitis lesions are also frequently seen in patients with RA, particularly various forms of dermal vasculitis. The most common are leukocytoclastic vasculitis and palpable purpura.
  • Cardiac manifestations
    • Echocardiographic evidence of a pericardial effusion or another pericardial abnormality is seen in almost 50% of patients who have no clinical symptoms of heart involvement.
  • Neurologic manifestations
    • As the peripheral nerve passes through a compartment that is also occupied by synovium or tendon sheaths, the possibility of nerve compression by synovitis or tenosynovitis exists.
    • Possible neuropathies that may exist include median nerve compression at the carpal tunnel, ulnar nerve compression at the Guyon canal, posterior interosseous nerve compression at the antecubital fossa, compression of the femoral nerve anterior to the hip joint, compression of the peroneal nerve adjacent to the fibular head, and compression of the interdigital nerve at the MTP joint.
    • The syndrome of mononeuritis multiplex is marked by an abrupt onset of a persistent peripheral neuropathy that is unaltered by either a change in joint position or a reduction in synovial inflammation.

Prognosis

• Disease factors that correlate with a poorer prognosis and a greater likelihood of joint destruction include the following:
• • Positive RF in serum IgA RF
  • Rheumatoid nodules
  • Being a young woman
  • Synovial fluid abnormalities (ie, WBC >50,000/mm³)

Patient Education

• Patient resources are widely available on the Internet.
• • See the Arthritis Foundation .
  • See the American College of Rheumatology.
• For excellent patient education resources, visit eMedicine's Arthritis Center and Muscle Disorders Center. Also, see eMedicine's patient education articles Rheumatoid Arthritis, Understanding Rheumatoid Arthritis Medications, Chronic Fatigue Syndrome, and Chronic Pain.

REFERENCES

Section 9 of 9

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

• 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. Primer on the Rheumatic Diseases. 11th ed. Arthritis Foundation;2000:155-168.
• Lipsky PE. Rheumatoid arthritis. In: Isselbacher KJ, Braunwald E, Fauci AS, et al, eds. Harrison's Principles of Internal Medicine. 13th ed. McGraw-Hill;1994:1648-1655.
• Nicholas JJ. Rehabilitation of patients with rheumatic disorders. In: Braddom RL, ed. Physical Medicine and Rehabilitation. 1996:711-727.
• Nicholas JJ. Physical modalities in rheumatological rehabilitation. Arch Phys Med Rehabil. Sep 1994;75(9):994-1001. [Medline].

Article Last Updated: Mar 22, 2006