Daniel J. Mazanec MD
Russell C. DeMicco DO
Edwin L. Capulong MD
Essentials of Diagnosis
Osteoarthritis (OA) is one of the most common musculoskeletal disorders and has a significant impact on functional activities. In the absence of a congenital joint deformity or serious trauma, OA is rare before 40 years of age. Prevalence increases with advanced age. Current data suggest that there are approximately 41 million Americans suffering from symptomatic OA. Men have a higher incidence and prevalence under the age of 50. This difference diminishes after the age of menopause. African Americans have a higher incidence of OA than whites.
OA is a multifactorial disorder resulting from a complex interplay of age, genetic, and environmental factors. Risk factors range from nonmodifiable to modifiable. Nonmodifiable risk factors include age, genetic predisposition, and congenital joint anomalies. Modifiable risk factors include diet, physical activity, obesity, and some metabolic disorders.
Joint trauma increases the risk of OA, particularly in the presence of joint malalignment, such as knee valgus deformity, leg length discrepancy, and joint instability brought about by quadriceps weakness or atrophy. In addition, strenuous physical activity and repetitive or mechanical stress (dystonia or spasticity) may hasten the development of arthritic changes in affected joints.
In the case of spasticity or dystonia, arthritic changes depend on the sites of involvement. In the neck, dystonia may produce cervical spondylosis, and in the hip, it may increase the risk of hip OA. In both cases, dystonia may develop at a younger than expected age because of persistent mechanical stress. In patients with prior trauma (eg, meniscal tear or hip injury), the risk of knee OA increases by five to six times, and hip OA by four times, respectively.
Age-related changes in the musculoskeletal tissues include calcification of joint cartilage, increased joint laxity due to muscle weakness and diminished joint proprioception. Overall, these factors may lead to increase propensity to arthritic changes and increase risk of falls in the elderly.
Increased concordance rates of clinical OA between monozygotic versus dizygotic twins support the notion of genetic predisposition to the disease. Clinical manifestations that may be suggestive of genetic predisposition include early age of onset, location (hands and hips) and family history.
Primary prevention of OA entails risk factor modification. Weight reduction, work environment modification for occupation-related disorders (cumulative trauma or repetitive stress disorders), and appropriate physical activity may reduce the risk of OA. Proper training, warm-ups, stretching exercises prior to physical activity, and maintenance of muscle strength may diminish trauma to the knees or hips, reducing the risk of OA.
Oxygen radicals have been associated with aging and variety of disorders, including OA, coronary artery disease, cataracts, and cancer. Nutritional factors play a major role in modulating oxygen radicals. In the joint, free oxygen radicals can cause damage to cartilage. Vitamin C, a potent antioxidant, may reduce the cartilage loss and retard progression of degenerative disease. In the Framingham study, persons with lower consumption of
vitamin C had an increased fourfold risk of OA. Other antioxidants, including vitamins A and E did not show the same efficacy as vitamin C. In fact, in recent studies, vitamin E did not demonstrate any effect on pain modulation. Vitamin A supplementation may increase risk of fragility fracture among males by a factor of seven.
Vitamin D may have a favorable effect on chondrocytes and may play a role in preventing arthritic changes, particularly in the knees. Suboptimal levels of vitamin D affect calcium metabolism and osteoblast activity affecting bone mineral density. Risk of knee OA may be increased as much as threefold in vitamin D-deficient patients.
Estrogen deficiency may play a role in progression of OA via stiffening of the bone, transmitting force to the overlying cartilage. In the Framingham study, estrogen replacement therapy has a moderate protective effect against worsening radiographic knee OA, although not statistically significant.
Secondary prevention is defined as limiting the progression of established degenerative joint disease and requires specific and prompt rehabilitation of injured joints with proper use of therapeutic exercise for rehabilitation. Education regarding activity modification in workplace or recreational activities may be helpful in retarding progression of degenerative joint disease.
OA is readily distinguished from rheumatoid arthritis (RA) and other inflammatory joint disorders by the pattern of joint involvement and the absence of systemic manifestations. In OA, pain is typically worse in the morning, with stiffness lasting a few minutes to less than 1 hour. Joint involvement is frequently asymmetric in a monoarticular to oligoarticular pattern, without evidence of systemic inflammation or extra-articular features (eg, fever, weight loss, rash, and presence of nodules).
In the hands, OA classically affects distal interphalangeal joints and less commonly the proximal interphalangeal joints or metacarpophalangeal joints. Other commonly affected joints include hips and knees as well as the cervical and lumbar spine. In the absence of trauma, elbows, wrists, and shoulders are less often affected (Table 14-1). On physical examination, bony enlargement of the affected joints is noted. Joint effusion may be present, and crepitus may be felt with joint motion.
Table 14-1. Characteristic Findings in Osteoarthritis, Rheumatoid Arthritis, Gout, and Pseudogout.
Table 14-2. Characteristics of Synovial Fluid in Noninflammatory, Inflammatory, and Septic Arthritis Compared with Normal Findings.
Laboratory findings in OA are usually normal and are performed to exclude other arthropathies. Laboratory studies indicated in selected patients include measuring uric acid levels, erythrocyte sedimentation rate, rheumatoid factor, antinuclear antibodies (ANA), and synovial fluid analysis. Synovial fluid analysis is helpful if infectious or crystalline arthritis must be excluded. In OA, synovial fluid is characteristically noninflammatory. White blood cell count and differential analysis of synovial fluid is used to differentiate inflammatory versus noninflammatory arthritis. Synovial fluid Gram stain and bacterial culture is helpful when infection is suspected (Table 14-2). Light polarizing microscopy can distinguish monosodium urate crystals, which appear as negatively birefringent versus calcium pyrophosphate crystals, noted as positively birefringent.
The clinical suspicion of OA is confirmed with plain radiographs of the affected joint. Typical findings include asymmetric joint space narrowing, osteophyte formation, degenerative cysts, and subchondral bone sclerosis. These radiographic changes can help classify the grade of OA (Table 14-3).
Severity of radiographic degenerative changes correlates imperfectly with clinical symptoms. OA is frequently asymptomatic and may coexist with other rheumatic disorders. Careful assessment for other causes of joint pain is required before attributing symptoms to osteoarthritic changes.
Magnetic resonance imaging (MRI) is more sensitive than plain radiographs for demonstrating cartilage loss, subchondral cyst formation, and osteophytes. In addition, MRI is more sensitive in identifying soft tissue injuries, including meniscal and ligamentous abnormalities.
In most cases, OA is easily distinguished from RA and other inflammatory arthritides by the absence of inflammation and laboratory abnormalities, by the pattern of joint involvement, and by radiographic changes. In contrast to RA and other inflammatory arthritides, OA is characterized by minimal articular inflammation without systemic manifestations. In contrast to OA, joint distribution in RA involves the wrist, proximal interphalangeal joint and metacarpophalangeal joint, sparing the distal interphalangeal joints.
Gouty arthritis is characterized by elevated serum uric acid levels, sudden onset of pain, erythema, and swelling most commonly affecting metatarsophalangeal joint of the big toe (podagra). Other joints may also be affected, including knees, ankles, and feet. Involvement is usually asymmetric (see Table 14-1). On physical examination, there is exquisite tenderness overlying an erythematous and swollen joint. In severe cases, tophaceous deposits can be seen in the ears, elbow joint, hands, knees, and feet. Synovial fluid examination for monosodium urate crystals is the definitive diagnostic test for suspected gouty arthritis. Another crystalline osteopathy, pseudogout (also called calcium pyrophosphate dihydrate deposition
[CPPD] disease) may also be identified by examination of synovial fluid. In addition to CPPD, a radiograph may show punctuate or linear densities in the articular hyaline or fibrocartilaginous tissues (see Table 14-1).
Table 14-3. Kellgren-Lawrence Classification of Radiographic Changes in Osteoarthritis.
The treatment of OA emphasizes a multidisciplinary approach, encompassing nonpharmacologic and pharmacologic treatment. The most important nonpharmacologic treatment for OA is exercise. Other options include weight loss, lifestyle modification, use of assistive devices, patient education, and occupational rehabilitation. The following medications may be helpful in treating OA: topical creams, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), tramadol, opioids, and intra-articular injections.
The primary objectives of treatment are reduction of pain, improvement of function, and preservation of joint structure. Nonpharmacologic and pharmacologic interventions should be exhausted before considering surgical therapy.
In general, it is better to rest an acutely painful joint for a few days before starting an active physical therapy or exercise program. The duration of a supervised therapeutic exercise is variable, but the emphasis should be the transition to a long-term home-based exercise maintenance program.
The goals of exercise may be specific to the affected joints. In the knees, for example, isometric strengthening of the quadriceps femoris muscles reduces joint instability and prevents disuse atrophy.
For short-term rehabilitation of the knee, closed kinetic chain exercises (feet are in contact with the floor or a solid surface) produce less stress at the knee joint and simulate functional movements; examples include walking, knee bending, seated leg presses, stair climbing, and stationary bicycling. Open kinetic chain exercises, on the other hand, involve exercises where the feet are not in contact with a solid surface, producing more tension in the soft tissues surrounding the knee joint; examples include knee extension, straight leg raising, and leg adduction in lateral decubitus position.
For short-term rehabilitation of knee OA pain, closed kinetic chain exercises are beneficial, but for long-term therapy (more than 3 months), open kinetic chain exercises may be more effective for pain control.
The use of aquatic therapy is beneficial for patients with lower extremity OA in whom weight-bearing exercise may be difficult.
Studies in people with knee OA have clearly demonstrated clinical benefit to a supervised fitness walking program. In one trial, supervised walking plus light stretching and strengthening exercises as well as patient education for up to 30 minutes three times weekly reduced knee osteoarthritic pain by 27% and increased the functional walking distance by 18% compared with baseline. At 1-year follow-up, patients who did not maintain an exercise program showed loss of functional benefits.
Table 14-4. Physical Activity Recommendations by the ACR for Persons with OA
Overall, weight loss and a moderate intensity exercise program prove to be beneficial not only in terms of increased cardiovascular endurance but also improving pain perception as reported in the Fitness Arthritis and Senior Trial (FAST). The American College of Rheumatology and American Geriatrics Society have developed guidelines for exercise in OA (Tables 14-4 and 14-5).
Capsaicin is a topical medication available without prescription. It stimulates unmyelinated C fiber afferent neurons causing a release of substance P. With prolonged use, capsaicin reversibly depletes stores of substance P from sensory nerve endings reducing the transmission of painful stimuli from the peripheral nerve fibers to the higher centers. Capsaicin can be an effective treatment of
acute exacerbations of osteoarthritic pain. For maximum benefit, it should be applied to the affected joint three or four times daily. Patients must be instructed to wash their hands carefully after each application as the drug may be very irritating if accidentally brushed into the eyes.
Table 14-5. Exercise Recommendations by the American Geriatric Society for Persons with Osteoarthritis.a
The American College of Rheumatology has recommended the use of acetaminophen as the first-line agent for mild symptomatic OA. Clinical trials have demonstrated significant improvement in pain and functional scores of patients with knee and hip OA treated with approximately 4 g of acetaminophen daily, comparable to treatment with naproxen 750 mg daily. In contrast, lower doses of acetaminophen are inadequate and generally inferior to treatment with NSAIDs in OA patients. A major advantage of acetaminophen versus NSAIDs is an excellent safety profile in doses less than 4 g daily. However, side effects may include liver enzyme elevation and drug sensitivity. In patients without underlying liver disease, dosages up to 4 g daily are well tolerated.
Nonsteroidal Anti-Inflammatory Drugs
Nonselective NSAIDs (cyclooxygenase [COX]-1 and COX-2) have been the mainstay in treating moderate to severe OA for many years because of their combined analgesic and anti-inflammatory actions. Risk factor assessment should be done in patients who are being considered for long-term therapy. A need for a gastro-protective agent should be considered in patients at high risk for gastrointestinal toxicity (Table 14-6).
COX-2 selective NSAIDs have been the medication of choice in OA patients at risk for gastrointestinal tox-icity. However, recent trials suggest a 1.5 to 2.0 times increased risk of cardiovascular events in patients receiving COX-2 selective NSAIDs, particularly rofecoxib and valdecoxib (both now withdrawn from the market), compared with nonselective COX inhibitors (see Chapter 3).
Table 14-6. Risk Factors for NSAID Toxicity.
Tramadol is a weak opioid receptor agent and nore-pinephrine and serotonin reuptake inhibitor. Tramadol is used for moderate to severe OA pain and should be considered in patients who do not respond to acetaminophen or NSAIDs. Tramadol is also used as an adjunctive therapy with NSAIDs. Maximum dosing for younger patients (younger than 65 years of age) is 400 mg/d in four divided doses, and for older patients (older than 65 years of age) is 300 mg/d in four divided doses. Side effects include drowsiness, constipation, and gastrointestinal symptoms (see Chapter 3). Tramadol is rarely associated with seizures but should be used with caution in high-risk patients or patients taking antidepressants. Low risk exists for abuse potential and withdrawal symptoms (see Table 3-2).
For patients with significant pain and functional impairment despite maximal nonpharmacologic treatment and nonopioid analgesic or NSAIDs, opioids should be considered. Advantages of opioids include superior analgesic effect for nociceptive pain and lack of significant end organ toxicity. Fears of tolerance and diversion have proved unfounded in recent studies of opioid therapy of
nonmalignant musculoskeletal disease. In patients at very high risk for NSAID-related gastrointestinal or renal adverse effects, opioid agents may offer a superior risk benefit profile.
Intra-articular corticosteroid injections are indicated in some patients with symptomatic OA; it is especially effective as adjunct treatment in patients in whom oral therapy is contraindicated or inadequate. In general, a large weight-bearing joint, such as the knee or hip, should not be injected more than 3 or 4 times per year. The agents most commonly used are methylprednisolone (80 to 120 mg per dose) and triamcinolone (20 to 40 mg per dose). These are usually combined with an anesthetic agent such as lidocaine (0.5 to 1%) or bupivacaine (0.25 to 0.5%). The volume and dose injected varies depending on the size of the joint.
Aseptic technique should be observed for all procedures. Before injecting, aspiration of synovial fluid for gross fluid examination may be performed if infection is a concern. If the fluid appears turbid or greenish-yellowish in color, injection should be aborted and synovial fluid analysis and culture should be performed.
If fewer than four injections are done per year, cartilage damage, pseudo-Charcot arthropathy, and avascular necrosis are rare complications. Patients should be warned of the more common complications, including infection, hemarthrosis, and corticosteroid-induced hyperglycemia in a diabetic patient.
Hyaluronan is a glycosaminoglycan responsible for synovial fluid viscoelasticity, which is reduced in OA joints by catalytic enzymes. Viscosupplementation therapy involves intra-articular injection of a hyaluronan derivative. Preparations available include hylan G-F 20 (administered weekly for 3 consecutive weeks) and sodium hyaluroniate (given as a weekly intra-articular injection for 5 weeks).
Clinical trials have produced conflicting results, but in a recent study, hylan G-F 20 showed significant analgesic effect compared with placebo as early as the third week continuing up to the eighth week following treatment. Previous uncontrolled cohort studies have demonstrated up to 1 year of symptomatic relief.
Experience with viscosupplementation in hip OA is limited, but recent reports suggest symptomatic relief and improvement of function at 3 months following injection. Adverse reactions include acute joint pain with effusion (particularly with hylan G-F 20 preparation), bleeding, and infection.
Older patients who have not responded to nonoperative treatment and are suffering from a moderate to severe disability due to pain should be considered for surgery. In younger patients in whom the risk of long-term failure or complication for artificial joints is high, delaying total joint arthroplasty, if possible, is the rule. Appropriate, “lesser” alternative procedures, such as arthroscopic debridement meniscectomy or high tibial meniscectomy for knee OA, should be considered.
Total hip and knee arthroplasty provide significant pain relief that usually translates to functional improvement. Perioperative mortality is below 1%. Early complications include deep venous thrombosis, pulmonary embolism, and infection. Late complications include aseptic loosening brought about by deterioration of cement (methylmethacrylate). Revision arthroplasty may be indicated in such patients.
The most popular alternative treatment for OA is glucosamine sulfate, which is derived from oyster or crab shells. Glucosamine has been proposed as both a preventive modality and treatment for mild OA. A proposed mechanism of action is stimulation of proteoglycan synthesis, which may either prevent or retard the clinical progression of OA. Preliminary studies suggest a significant analgesic effect in about two-thirds of patients, comparable to NSAID therapy. In addition, a small placebo-controlled trial found reduced progression of radiographic knee OA in persons treated with glucosamine. The recommended therapeutic dose is 1500 mg of glucosamine daily. Glucosamine is well tolerated with few side effects. A combination of glucosamine and chondroitin has not been shown to have significant benefit versus glucosamine alone.
S adenosylmethionine (SAMe) is reported to increase production of proteoglycans, potentially benefiting patients with OA. Randomized trials demonstrating efficacy in OA have not been reported. SAMe is claimed to be as effective as NSAIDs in terms of symptom relief, with fewer side effects. SAMe (800 mg/d orally in two doses) is primarily advocated for mild OA. SAMe may take up to 1 week to produce clinical effects. Side effects include nausea and skin irritation. Other proposed potential indications include fibromyalgia and depression.
In a recent randomized, controlled trial, acupuncture was demonstrated to be efficacious in treating osteoarthritic knee pain. The basis for the analgesic effect of
acupuncture is postulated to be either release of endogenous opioids or, alternatively an interference with pain transmission based on the gate theory of pain. In addition, absence of known side effects makes acupuncture an attractive treatment option for patients unresponsive to or intolerant of more traditional therapy, including NSAIDs.
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Essentials of Diagnosis
RA is a chronic progressive autoimmune disease with varying systemic features that affects 2.1 million people in the United States. RA causes pain, progressive joint destruction, fatigue, loss of mobility, and inability to perform activities of daily living. The primary pathology is a hypertrophied inflammatory synovium ultimately leading to erosive joint disease with pain, loss of function, and progressive disability. RA might be better termed “rheumatoid disease” because of its multiple extra-articular manifestations, including pleuritis, pericarditis, vasculitis, and pulmonary nodules among others (Table 14-7).
RA accounts for more than 9 million physician visits per year and at least 250,000 hospitalizations. The
substantial economic burden of RA is associated with both treatment costs and lost productivity and employment. Furthermore, RA significantly reduces life expectancy; age-adjusted mortality rates are increased by about 50%.
Table 14-7. Extra-articular Manifestations of Rheumatoid Arthritis.
Epidemiologic studies indicate that the prevalence of RA is 0.5 to 1% of the adult populations in the United States and Europe. Certain Native American tribes show prevalence up to 5.3%. Prevalence increases with age and peaks between the ages of 40 and 60 years.
Joint pain and stiffness significantly impact quality of life in people with RA. Many people experience pain that impairs physical and psychological function despite receiving appropriate and aggressive treatment for underlying disease. Pain is sometimes viewed as an indication of disease activity even though disease activity and severity do not predict intensity of pain or level of function of the individual.
Most commonly, RA follows a progressive course punctuated by disease flares. Spontaneous lasting remission is rare, occurring in less than 5% of patients. Specific criteria for defining clinical remission include the following:
Early diagnosis and treatment of RA are crucial to maintaining optimal functional status in most patients. Recent studies describe development of erosive disease within the first few months of disease. Early and aggressive treatment may limit joint damage, preserving movement and ability to work while reducing medical costs and potential surgery.
RA is a disease of an aberrant immune response in a genetically predisposed host that leads to chronic progressive synovial inflammation and destruction of the joint architecture. The hallmark of RA is the proliferation of inflamed synovium, which spreads over the articular surface as a pannus and damages cartilage, bone, and joint capsule. Although research continues to broaden the understanding of the pathophysiologic mechanisms involved in the development and progression of RA, no clear triggering agent has been identified.
Although the precise cause of RA is unknown, hormonal, genetic, and environmental risk factors have been identified. The incidence of RA increases with age. However, incidence begins to decline when people reach their mid-70s. Females are 2 to 3 times more likely to develop rheumatoid arthritis than males. Genetic factors also play a role in some patients. There is a well-established association between RA and HLA-DR4 with an increased relative risk of in 4 to 5 patients with this allele. Recent research has demonstrated an association between RA and Runt-related transcription factor 1 (RUNX1), organic cation transporter gene SLC22A, and peptidylarginine deiminases citrullinating enzyme 4 (PADI4). Of lifestyle factors, only smoking has been associated with an increased risk of developing RA.
Since the precise etiology of RA has not been identified, preventing the disease is not possible. However, the destructive capacity, pain and stiffness, and resultant disability of RA may be reduced with appropriate recognition and early treatment.
Many nonspecific 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.
-The 1987 revised criteria of the American College of Rheumatology for RA were developed to aid with clinical assessment and performance of clinical trials. RA is diagnosed in patients who meet at least four of the following criteria (criteria 1 through 4 must be present for at least 6 weeks):
RA manifestations may be articular (joint pain, swelling, and stiffness) or nonarticular (see Table 14-7). Nonarticular findings may be classified as systemic (fever, fatigue) or nonsystemic (pleuritis, vasculitis, Felty syndrome, and Sjögren syndrome).
Articular RA can start in any joint, but it most commonly begins in the smaller joints of the fingers, hands, and wrists. Joint involvement is usually symmetric. Joints typically involved include the metacarpophalangeal, proximal interphalangeal, and wrists with sparing of the distal interphalangeal joints. Carpal tunnel syndrome may be an early manifestation of RA. The temporomandibular joint may also be involved. Joints are painful and typically swollen and warm. Prolonged stiffness in the joints in the morning or after prolonged inactivity is characteristic of inflammatory arthritis such asRA.
Table 14-8. Diagnostic Criteria for RA Established by the American College of Rheumatology.
-Actively inflamed joints are swollen, warm, and tender to palpation. On palpation of the joint, a boggy sensation results from the combination of synovial proliferation and fluid. Synovial proliferation in the flexor tendons of the fingers fills the palm, giving it a flat appearance. Joint range of motion is initially limited by pain and later by contractures. Grip strength is reduced. Carpal tunnel syndrome and synovitis at the elbow manifested as inability to fully extend may be early indications of presence of RA. Ulnar deviation of the fingers at the metacarpophalangeal joint is a common deformity in established disease that results from radial deviation of the wrist and slippage of the extensor tendons to the ulnar side of the metacarpophalangeal joints. Another deformity of the hand that develops in chronic disease is the swan-neck deformity, which results from the flexion of the distal interphalangeal joint and metacarpophalangeal joint with hyperextension of the proximal interphalangeal joint. The boutonniere deformity is caused by avulsion of the extensor hood over the proximal interphalangeal joint. In advanced disease, subluxation and flexion deformities are common and involve the knees, ankles, elbows, wrists, shoulders, hands, and feet.
-Rheumatoid factor is found in the serum of about 85% of persons with RA. In the individual patient, rheumatoid factor titer is of limited prognostic value, and serial titers are of no value in following the disease process. Higher rheumatoid factor titers tend to correlate with more severe and unremitting disease, more radiologic abnormalities, nodules, extra-articular lesions, and worse functional ability. Conversely, seronegative patients generally have less destructive disease. Rheumatoid factor may be negative in early stages of disease and is not specific for RA. Rheumatoid factor may be present in other connective tissue disorders such as systemic lupus erythematosus (SLE), Raynaud disease, scleroderma, Sjögren syndrome as well as autoimmune thyroid disease and chronic infections such as tuberculosis and endocarditis.
-Many patients with RA have IgG antibodies to citrullinated peptides (anti-CCP antibody). Such anti-CCP antibodies appear relatively early in RA, are highly specific for the disease (98%), and can be measured by quite reproducible, readily available assay systems. Several experimental observations suggest that the immune responses to citrulline could play a significant role in the pathogenesis of RA
inflammation. In contrast to RF, anti-CCP antibodies fluctuate with activity of the disease.
-Acute-phase reactants such as the erythrocyte sedimentation rate and C-reactive protein measure the inflammatory response and correlate well with the degree of synovial inflammation. They are useful for following the course of inflammatory activity in an individual patient or monitoring response to treatment. Erythrocyte sedimentation rate is an indirect measure of inflammatory proteins and is not reliable in patients with significant anemia.
Thrombocytosis and eosinophilia occur more often in patients with severe disease, high rheumatoid factor titer, rheumatoid nodules, and extra-articular manifestations. Normochromic normocytic anemia of chronic disease is frequently seen in active RA.
-Early radiographic changes in RA include swelling of the soft tissues and periarticular osteopenia. With progressive disease, erosive changes appear. Baseline radiographs of hands or feet should be obtained within 3 months of diagnosis of RA and every 12 to 24 months thereafter to assess development or progression of destructive erosive change.
Since tenosynovitis of the transverse ligament of C1, which stabilizes the odontoid process of C2, may produce significant C1-2 instability, patients with RA planning surgery with general anesthesia (intubation) should be evaluated with a set of lateral flexion and extension views of the cervical spine.
-New RA lesions may be detected 1 to 5 years earlier with MRI than with conventional radiography. MRI is particularly useful in identifying synovitis.
It is important to assess functional status and monitor clinical disease activity during treatment. Traditional historical measures of rheumatoid disease activity include duration of morning stiffness (decreases in response to treatment) and time of onset of systemic fatigue (occurring later with response to treatment). Patient self-assessed pain level using a Visual Analogue Scale is very useful in monitoring disease activity and response to treatment. However, pain levels may be significant due to residual joint destruction even without active disease. Less specific historical indicators include need for supplemental or “rescue” analgesics and lost work days. Clinical measures of disease activity include counting the number of swollen joints or in the absence of fixed deformity, range of motion of involved joints. Several well-validated self-administered instruments are available to monitor functional status in RA patients. These include the Health Assessment Questionnaire and the Arthritis Impact Measurement Scale.
Table 14-9 outlines the key distinguishing features of the seven conditions discussed in this section, including OA, systemic lupus erythematosus (SLE), polymyalgia rheumatica (PMR), infectious arthritis, crystalline arthritides, seronegative spondyloarthropathies, and
fibromyalgia. Table 14-10 lists a more detailed differential diagnosis that is divided into acute and chronic inflammatory disorders.
Table 14-9. Key Distinguishing Features.
Table 14-10. Differential Diagnosis of Rheumatoid Arthritis.
OA is differentiated from RA by onset later in life, pattern of joint involvement (proximal interphalangeal, distal interphalangeal, monoarticular involvement of hip or knee, propensity for neck and low back), and absence of inflammatory signs and symptoms. OA is rarely erosive and lacks the morning gelling and systemic features associated with RA.
SLE and other connective tissue diseases may mimic RA with symmetric joint inflammation. SLE is not typically erosive. Clinical manifestations of SLE (eg, fever, serositis, dermatitis, nephritis) and serologic findings (eg, cytopenia, ANA seropositivity, anti-DNA seropositivity) assist with making the correct diagnosis.
PMR and giant cell arteritis may present with symmetric polyarthritis. RA in the elderly may mimic PMR. The presence of arteritic signs or symptoms such as headache, joint claudication, or visual change with predominant shoulder and hip girdle stiffness support the diagnosis of PMR.
Infectious arthropathies are an important consideration in the setting of fever and polyarthritis. Joint aspiration as well as synovial fluid cultures and blood cultures are often helpful in establishing the diagnosis of bacterial arthritis. Lyme disease may present with myalgias and arthralgias in the setting of erythema chronicum migrans and history of tick bite. Viral arthritides (parvovirus B19, rubella infection, or immunization) often distinguish themselves by history of exposure, accompanying rash, and self-limited course.
Polyarticular crystal arthropathies, such as gout and pseudogout, may mimic RA. Synovial fluid analysis is usually definitive in crystalline arthritis if performed early during an acute attack. Erosions may be seen in gouty arthritis but they differ from the marginal erosive changes of RA. Chondrocalcinosis may be apparent with pseudogout.
The seronegative spondyloarthropathies include enteropathic arthritides, psoriatic arthritis, ankylosing spondylitis, and reactive arthritis. Seronegative spondyloarthropathies characteristically present with asymmetric inflammatory disease of the large joints. Involvement of the lumbosacral spine, absence of small-joint disease, and sausaging of the digits support the diagnosis of seronegative spondyloarthropathies. Coexisting uveitis, urethritis, psoriasis, or inflammatory bowel disease also favor a diagnosis of seronegative spondyloarthropathies.
Although noninflammatory, fibromyalgia may present with diffuse symmetric arthralgias and stiffness at rest. Normal laboratory and imaging studies with the absence of synovitis help differentiate fibromyalgia from RA. Fibromyalgia coexists in 10 to 15% of the patients in whom rheumatic diseases such as RA and SLE are diagnosed.
Medications used in the treatment of RA may be categorized as analgesics, anti-inflammatory agents, or disease-modifying antirheumatic drugs (DMARDs)
(Table 14-11). In general, analgesics and anti-inflammatory drugs relieve symptoms but do not retard joint damage. Typically, they are more rapidly acting in providing symptomatic benefit in comparison to DMARDs, though newer anti-tumor necrosis factor (TNF) agents also often provide prompt relief of pain and stiffness.
Table 14-11. Pharmacologic Treatment for Rheumatoid Arthritis
Most patients are initially treated with a combination of an anti-inflammatory agent and one or more DMARDs. Pure analgesics have an important role in supplementing symptom control, particularly pain, and as substitutes for NSAIDs in patients who are intolerant or who are at high-risk for adverse effects. Intra-articular administration of a corticosteroid is important adjunctive therapy in some patients with active disease in an isolated joint. In patients with a polyarticular flare, systemic corticosteroids, either orally or parenterally may provide acute symptom control.
Immediate therapy with DMARDS not only improves symptom control but more importantly retards the progression of erosive, destructive joint disease at an earlier stage. The American College of Rheumatology currently recommends DMARD therapy within 3 months of disease onset. Hopefully, this more aggressive approach will result in preservation of joint structure and function, reduced long-term disability, reduced health care costs and preservation of economic productivity.
In the management of RA, nonpharmacologic treatment must not be neglected. Patient education, physical and occupational therapy, activity modification, and psychosocial support also play important roles in optimizing patient outcome.
Surgical treatment, particularly joint replacement, has dramatically improved the quality of life of many patients with RA over the past 30 years.
NSAIDs have long been used as initial therapeutic agents in RA for rapid symptom control. These agents inhibit to some degree one or both COX enzymes (COX-1 and COX-2). The traditional NSAID adverse effects gastropathy and nephrotoxicity are primarily associated with inhibition of COX-1 synthesis. Older, nonselective NSAIDs affect both enzymes, resulting in greater risk of COX-1 adverse effects.
Gastric or duodenal ulcers that can be seen endoscopically develop in 15 to 20% of persons taking nonselective NSAIDs. More significant symptomatic lesions develop in 2 to 4% with 1 to 2% noting ulcer complications of bleeding or perforation. Risk factors for NSAID gastropathy include older age, higher dose NSAID, previous history of peptic ulcer disease, previous use of antacids or H2-antagonists, concomitant use of corticosteroids, and more severe inflammatory disease.
Selective COX-2 inhibitors are associated with an approximate 50% reduction in prostaglandin-mediated clinical gastrointestinal toxicity in comparison to nonselective agents. However, accumulating evidence suggests therapy with newer selective COX-2 agents (ie, rofecoxib and valdecoxib, which are no longer available) is associated with a significant increase in cardiovascular adverse events including myocardial infarction and stroke, particularly at higher doses and in higher risk patients. No difference in efficacy between COX-2 inhibitors and nonselective drugs has been demonstrated. In addition, no difference in renal toxicity between the two classes of NSAIDs has been shown.
Based on currently available data, patients with rheumatoid disease who require NSAID therapy but who are at high risk for gastrointestinal adverse effects and who have no history or risk factors for cardiovascular events may be treated with celecoxib. Alternatively,
a nonselective NSAID may be combined with a proton pump inhibitor such as omeprazole for gastric protection. In patients with significant cardiovascular risk factors or history, selective COX-2 NSAIDs should be avoided.
Unfortunately, co-therapy with low-dose aspirin for cardiovascular prophylaxis in such patients negates the COX-2 inhibitor's beneficial reduction of gastrointestinal toxicity. Low-dose (<10 mg prednisone equivalent) corticosteroid therapy combined with a pure analgesic such as acetaminophen represents a reasonable alternative to an NSAID for management of inflammatory symptoms.
Corticosteroids may be administered systemically or locally for treatment of RA. Low-dose (<10 mg prednisone equivalent) corticosteroids taken orally are typically combined with other medications in initial management of RA. Corticosteroids provide prompt suppression of inflammation and may be viewed as “bridging therapy” while treatment with more slowly acting DMARDs is being initiated. Many patients remain on long-term corticosteroid therapy, however, posing risk of long-term corticosteroid toxicity, particularly cataracts and bone loss (osteoporosis). In persons in whom longer term use of corticosteroid therapy is anticipated, baseline bone density measurement is recommended and prophylactic treatment with calcium supplementation, vitamin D, and antiresorptive therapy such as diphosphonates should be considered.
For patients experiencing generalized “flares” of disease activity, a short, rapidly tapering course of an oral corticosteroid may provide prompt, short-term relief of severe polyarticular and systemic symptoms. Alternatively, intramuscular injection of a “depo” corticosteroid may provide similar benefit. Use of such “pulse” treatment should be reserved for episodic treatment of severe flares and probably limited to 2 to 3 times yearly. Excessive administration of intramuscular or pulse corticosteroids is associated with risk of iatrogenic Cushing syndrome as well as the full range of corticosteroid toxicity and should prompt reevaluation of the patient's regular rheumatoid therapy.
Intra-articular injection of corticosteroid may effectively reduce inflammatory pain and swelling in joints refractory to systemic therapy. Injection into any single joint should be limited to three or four times within 1 year. Systemic absorption of corticosteroid occurs and diabetic patients should be warned about the possibility of transient hyperglycemia.
The defining characteristic of a DMARD is the ability to retard erosive joint damage by controlling synovial inflammation. For most older DMARDs, the precise mechanism of action is unknown.
The American College of Rheumatology currently recommends starting DMARD therapy within 3 months of disease onset. Most patients should be started on DMARD therapy at the time of initial diagnosis. DMARDs may be used as monotherapy or in combinations depending on the disease severity, prognostic features, costs, and comorbidity. In addition to slowing radiographic progression of disease, DMARDs are more effective than NSAIDs in reducing systemic symptoms such as fever or fatigue.
-These agents, including hydroxychloroquine and chloroquine, are less potent DMARDs often used to treat early or mild RA in combination with an NSAID. Hydroxychloroquine is well tolerated but slow-acting, which is a characteristic feature of most older DMARDs. Patients may not notice therapeutic effect for 3 to 6 months. If total daily dose is limited to 5.5 mg/kg/d and never exceeds 400 mg/d, serious retinal toxicity is rare. Annual ophthalmologic examination is required in all patients, however, to detect retinopathy.
-Methotrexate is a folate analog that blocks DNA synthesis, though its antirheumatic effect may be related to other anti-inflammatory properties of the drug.
For most patients with active RA, methotrexate remains the first-line choice because of its established and sustained efficacy with manageable toxicity as well as a substantial cost advantage over newer biologic agents. Approximately 60% of patients with RA respond to methotrexate, which is comparable to the results seen with newer biologic agents, such as etanercept.
Methotrexate is typically administered in a once weekly oral dose of 7.5 to 15 mg. Escalation of dose by 2.5 to 5.0 mg increments based on clinical response should be considered at 4- to 6-week intervals. In the absence of significant toxicity, the dose of methotrexate may be increased to 20 to 25 mg weekly based on the clinical response. Clinical response to the drug occurs with 4-12 weeks. Clinical indicators of response include reduced morning stiffness and systemic fatigue as well as the number of swollen, tender joints. A significant proportion of patients with early RA can achieve disease control for at least 1 year by taking methotrexate alone.
Methotrexate is excreted by the kidneys and is contraindicated in patients with creatinine levels over 2.0 to 2.5 mg/dL. Patients who consume significant amounts of alcohol on a regular basis should not be treated with methotrexate because of risk of hepatic toxicity. In general, limiting alcohol intake to the equivalent of a glass of wine once or twice weekly is reasonable advice for patients taking methotrexate. Regular monitoring of liver function tests (complete blood count, aspartate
aminotransferase, and alanine aminotransferase) is appropriate, but hepatic fibrosis may occur in the face of normal enzymes. Regular liver biopsy to monitor for fibrosis is not routinely recommended at antirheumatic doses of methotrexate.
In patients in whom methotrexate is contraindicated, initial therapeutic alternatives include sulfasalazine, hydroxychloraquine, or even etanercept or adalimumab, depending on the severity of the disease.
Methotrexate may be combined with anti-TNF drug therapy (etanercept, infliximab, or adalimumab). Recent trials suggest combined methotrexate and anti-TNF therapy is more efficacious than monotherapy with either agent. However, long-term toxicity of combined therapy is unknown, (ie, is the risk of lymphoma increased?). Also, cost-benefit analysis of combined versus monotherapy needs further study. Patients with active rheumatoid disease who do not respond to anti-TNF therapy alone or in combination with methotrexate should be considered for treatment with anakinra (see below).
-Leflunomide is a pyrimidine synthesis inhibitor with a clinical profile very similar to methotrexate. Efficacy that is similar to methotrexate, including reduction in radiographic erosive disease, has been demonstrated. Like methotrexate, hepatic toxicity occurs, elevating liver enzymes. Diarrhea is a common side effect of the drug, which may require discontinuation of treatment. Leflunomide therapy is initiated with a 3-day loading dose (100 mg/d) and then continued in a single 20-mg daily dose. Like methotrexate, improvement in signs and symptoms occurs within about 6 weeks. Regular monitoring for thrombocytopenia and liver enzyme elevation should be performed.
-Though initially developed as an anti-inflammatory antirheumatic drug in the precorticosteroid era more than 60 years ago, sulfasalazine has been more widely used to treat inflammatory bowel disease. Sulfasalazine demonstrates modest DMARD qualities including reduction in radiographic erosive disease and improvement in articular inflammatory signs and symptoms. The mechanism of action of the drug in RA is not known, but the metabolites of the drug-sulfapyridine and 5-ASA-have a variety of effects on cellular immune function.
Sulfasalazine is best administered in an enteric-coated form to reduce the risk of gastrointestinal toxicity. Therapy is initiated at a dose of 500 mg/d with escalation over 1 to 2 months to the full antirheumatic dose of 2000 mg/d. Sulfasalazine is slow acting with approximately 3 months of therapy required before clinical improvement occurs. Toxicity of sulfasalazine includes gastrointestinal distress (minimized by the enteric-coated preparation) and, rarely, agranulocytosis. Complete blood count should be performed regularly to monitor for toxicity.
Azathioprine, cyclophosphamide, and cyclosporine have largely been replaced as treatment for severe, active RA by newer biologic therapies including anti-TNF agents (etanercept, infliximab, adalimumab) and interleukin receptor antagonists (anakinra). In general, use of these older immunosuppressives is limited primarily by significant toxicity. Cyclosporine commonly causes hypertension and renal impairment, complicating its use with methotrexate in RA. Cyclophosphamide is an alkylating agent with significant toxicity. Hemorrhagic cystitis, bone marrow suppression, and risk of lymphoma are major concerns. Azathioprine is the most commonly used drug in this group, often in combination with methotrexate. Bone marrow suppression and concerns regarding oncogenicity limit its usefulness.
The newest agents available for treatment of RA are targeted at proinflammatory cytokines, which are central to the pathogenesis of the disease. Sometimes referred to as “biologics” for “biologic response modifiers,” these presently include three drugs targeted at TNFα and one interleukin-1b antagonist. TNFα and interleukin-1b are secreted by synovial macrophages and T helper lymphocytes and play a major role in pannus development and joint destruction. They stimulate proliferation of synovial cells and production of collagenase, which degrades cartilage contributing to erosive joint damage.
TNFα also promotes recruitment of other inflammatory cells and increased secretion of interleukins, perpetuating the inflammatory process. By specifically interfering with this inflammatory cascade, the biologics produce prompt and significant clinical effects in patients with RA. The cost of anticytokine therapy is substantial, exceeding $12,000 annually. This represents a significant consideration in choice of first-line therapy for many patients.
-Etanercept is a TNFα receptor fusion protein that binds soluble TNFα, inhibiting its ability to bind to cellular surface receptors and exert its proinflammatory effects. Etanercept produces comparable clinical improvement to methotrexate (20 mg weekly) in the signs and symptoms of RA but does so much more rapidly, often within 2 weeks of the first dose. Long-term studies comparing methotrexate and etanercept suggest comparable benefits in reducing radiographic damage to joints. Combined therapy with etanercept and methotrexate is more effective than either drug alone. Long-term follow-up studies now beyond 6 years suggest
continued efficacy and safety of combined methotrexate and etanercept.
Etanercept is administered by subcutaneous injection, either in a single 50-mg weekly dose or in two 25-mg split weekly doses with comparable efficacy. Mild injection site reactions occur in about one-third of patients, particularly during early therapy. Opportunistic infections, which may be life-threatening rarely occur in patients treated with etanercept.
Reactivation of tuberculosis is a particular concern and patients should be screened for tuberculosis by history and with a purified protein derivative (PPD) skin test before starting therapy. Demyelinating disease and non-Hodgkins lymphomas have rarely been reported in patients using etanercept. The incidence of non-Hodgkins lymphomas in etanercept-treated patients is comparable to the RA population in general. Cytopenias have rarely been reported.
-Infliximab is a chimeric (murine/human) IgG monoclonal antibody to TNFα which in combination with methotrexate has comparable efficacy to etanercept in the treatment of RA. The drug is administered by intravenous infusion at a dose of 3 to 5 mg/kg at intervals of 4 to 8 weeks. Clinical response is rapid. Antibodies to the drug develop in about 40% of patients but do not appear to affect efficacy or safety.
Infusion reactions characterized by headache, rash, nausea, or hypotension may occur and are usually mild. As with etanercept, serious infections, particularly tuberculosis, have been reported with infliximab therapy. Most cases represent reactivation of dormant disease and occur within 6 months of starting infliximab therapy. Ex-trapulmonary disease is common. Screening as discussed with etanercept is mandatory in patients before initiating treatment. Anticytokine treatment should be suspended in patients in whom a serious infection is developing. Vaccination with a live vaccine is contraindicated during treatment with all TNF inhibitors. Higher doses of infliximab (10 mg/kg) in patients with heart failure have caused worsening of the failure. As with etanercept therapy, infliximab treatment has been associated with development of autoantibodies, including anti-double-stranded DNA. Rarely, a lupus-like reaction has been seen with either infliximab or etanercept. Since all patients receiving infliximab are also treated with methotrexate, appropriate monitoring for methotrexate adverse effects, as discussed earlier, is required.
-Adalimumab is a fully human recombinant IgG antibody to TNFα with similar efficacy and toxicity to etanercept and infliximab. Adalimumab is effective as monotherapy or in combination with methotrexate. Adalimumab provides additional benefit to patients taking a stable dose of methotrexate alone. Adalimumab is administered by subcutaneous injection in a recommended dose of 40 mg every other week.
-Interleukin-1 receptor antagonist protein (IL-1Ra) is a naturally occurring IL-1 inhibitor that binds to the IL-1 receptor without producing cellular activation, effectively blocking the proinflammatory effects of IL-1. Anakinra is a human recombinant IL-1 receptor antagonist that has demonstrated efficacy in patients with RA. Clinical benefits and radiographic effects are generally fewer than those with anti-TNFα agents. Anakinra is administered daily by subcutaneous injection.
A significantly increased risk of serious infection has been seen when anakinra is combined with anti-TNFα drugs such as etanercept. Combination with older DMARDs such as methotrexate or sulfasalazine appears safe.
Pure analgesics play an important role in arthritis pain management. In patients with active RA, inflammatory pain is best managed with NSAIDs, corticosteroids (systemic or intra-articular) and ultimately with control of disease by a DMARD such as methotrexate. The presence of active inflammation is suggested by prolonged morning stiffness, systemic fatigue, and palpable joint swelling (synovitis) and warmth. However, some patients with active disease require additional analgesic treatment during initiation of DMARD therapy or because of toxicity or intolerance to NSAIDs or corticosteroids. For some patients, full dose acetaminophen is adequate adjunctive treatment but many require at least transient or supplemental treatment with an opioid analgesic.
Some patients with RA who have responded well to DMARD therapy still experience significant pain as a consequence of significant joint damage from quiescent prior synovitis. In these patients, inflammatory signs and indicators are absent. These symptoms do not require escalation of anti-inflammatory or DMARD therapy.
Treatment of pain in persons with controlled or “burnt-out” RA is similar to pain management discussed for OA and involves local (topical or intra-articular) modalities, assistive devices, as well as nonopioid and opioid analgesics.
Gold compounds administered parenterally or orally have demonstrated efficacy and a long history of use in RA but are rarely used at this time. Less than 10% of patients continue taking gold 5 years after starting therapy in contrast to much higher rates of patients treated with methotrexate or anticytokine drugs. For similar reasons, D-penicillamine use for RA has declined precipitously as well.
Minocycline is an antibiotic that has been shown to favorably affect signs and symptoms of RA. Its mechanism
of action is unknown but the drug has anti-inflammatory properties. No disease-modifying effect has ever been demonstrated.
A comprehensive approach to treatment of rheumatoid arthritis is required to ensure the efficacy of the management plan, ultimately providing decreased pain, increased mobility, and improved patient satisfaction and quality of life.
-Patient education is essential early in the disease course and on an ongoing basis. Because RA may make a patient prone to fatigue and muscle weakness, energy conservation and joint protection techniques are important in limiting pain while maintaining function. Education is directed at patients and family members.
-Muscle strengthening or aerobic exercise programs also play an important role in maintenance of function and optimizing outcome. All individuals should be encouraged and supported to participate in the minimum level of physical activity recommended by the US Surgeon General-at least 30 minutes of moderate physical activity on most days of the week. Persons with OA and RA who have difficulty in maintaining minimum levels of physical activity may be referred to physical or occupational therapy to evaluate and reduce impairments in range of motion, flexibility, strength, and endurance as well as receive instruction in joint protection strategies. Therapists will properly prepare an individual for successful participation in a community-based or self-directed exercise program. In addition, modalities such as splinting, ice, heat, paraffin baths (see Chapter 6), and massage have been shown to be useful for pain management in adults with RA. Transcutaneous electrical nerve stimulation (TENS) has been shown to improve wrist function while reducing pain with minimal adverse effects in RA patients.
-A patient's thoughts, feelings, emotions, and behavior, and his or her family's response, can influence the arthritis pain experience. Therefore, education about pain, pain management options, and self-management programs should be communicated to the patient and family as an integral and cost-effective part of treatment. The degree to which RA affects daily activities depends in part on how well the patient can cope with the disease. Cognitive-behavioral therapy may be used to reduce pain and psychological disability and to enhance self-efficacy and pain coping. Use of assistive equipment or devices (Table 14-12) is another adjunctive treatment to help maintain function while minimizing or reducing pain.
-People with arthritis should be advised to maintain an ideal body weight and ad here to a balanced diet containing adequate amounts of protein, fat, vitamins, and minerals. Adults should lose weight if their body mass index is greater than 30 and follow a weight management program. Fish oil supplements, fasting, and a vegetarian diet may reduce pain in some patients with RA. Evidence from double-blind, placebo-controlled randomized clinical trials supports dietary omega-3 polyunsaturated fatty acids in reducing morning stiffness and joint tenderness in RA. However, the clinical application of fish oil in the treatment of RA is not well-defined in terms of dose and duration of therapy. Fish oil has not been shown to benefit patients with OA.
Table 14-12. Assistive and Adaptive Equipment to Help Patients with Rheumatoid Arthritis.
Fasting has been shown to reduce pain and stiffness associated with RA. However, most persons relapse as food is reintroduced. Fasting followed by a vegetarian diet for 1 year has shown a reduction in the number of tender joints and duration of morning stiffness. Reduction of
joint inflammation and pain was sustained if vegetarian diet was followed. There is insufficient evidence of the benefits of electromagnetic field therapy to recommend its use in the management of pain related to arthritis. Prayer and spirituality may also play a role in reduction of pain in patients with RA.
Indications for surgery in RA include loss of function and pain that is refractory to medical management. For optimal functional results, people with disabling arthritis should be referred for surgical care prior to the onset of joint contracture, severe deformity, advanced muscular wasting, and deconditioning rather than as a last resort. If the patient has severe pain in the hips and knees that significantly limits activities despite any drug or nondrug therapies, with significant radiographic damage, orthopedic referral should be considered.
-Joint replacement surgery restores the integrity and functional power of a joint. For many people with RA whose joints are severely damaged, joint replacement surgery can restore joint function, reduce pain, or correct a deformity. Hip and knee total joint arthroplasty provide major improvement in musculoskeletal function and improved quality of life with benefit of complete pain relief in most cases. Because of their documented effectiveness, these procedures should be offered to patients when nonsurgical management becomes less effective and preferably before deconditioning becomes severe and difficult to reverse.
-Arthrodesis is the surgical removal of the articular surface and fixation of the two bones to pro mote bone fusion at the prior joint. Joints treated with total joint arthroplasty (hip, knee, shoulder, and less frequently the elbow) are rarely treated with arthrodesis because of the likelihood of functional deficit. The most successful arthrodesis is performed on joints where replacement is not an option, such as the subtalar, calcaneocuboid, talonavicular, midfoot joints of the feet, and the lesser joints of the hands and feet.
-Synovectomy is sometimes performed to remove inflammatory tissue and retard joint destruction. Synovectomy of selected joints may transiently alleviate symptoms and improve function in the first year after operation. Long-term benefits of synovectomy are less clear and concurrent medical therapy must be maintained. Removal of synovial tissue from the wrist and dorsal tendon sheath and resection of the ulnar head might prevent rupture of extensor tendons in patients at risk.
Table 14-13. Poor Prognostic Indicators for Patients with Rheumatoid Arthritis
The course of the disease varies considerably among individuals. Poor prognosis is suggested by earlier age at disease onset, high titer of rheumatoid factor, elevated erythrocyte sedimentation rate, and swelling of more than 20 joints. Extra-articular manifestations of RA, such as rheumatoid nodules, Sjögren syndrome, episcleritis and scleritis, interstitial lung disease, pericardial involvement, systemic vasculitis, and Felty syndrome, may also indicate a worse prognosis (Table 14-13).
Studies have shown that patients with active, polyarticular, rheumatoid factor-positive RA have a greater than 70% probability of joint damage or erosions developing within 2 years of the onset of disease. Since studies have demonstrated that DMARDs may alter the disease course in patients with recent-onset RA, particularly those with unfavorable prognostic factors, aggressive treatment should be initiated as soon as the diagnosis has been established. Frequently, the disease can be controlled with a combination of treatments. Treatment may vary depending on the severity of the symptoms.
Remission is most likely to occur in the first year and the probability decreases as time progresses. About 20% of persons will have experienced remission by 10 to 15 years from diagnosis.
Between 50 and 70% of patients with RA will remain capable of full-time employment. After 15 to 20 years, only 10% of patients are severely disabled, and unable to perform simple activities of daily living (washing, toileting, dressing, eating). The average life expectancy of patients with RA may be shortened by 3 to 7 years. Patients with severe forms of RA may die 10 to 15 years earlier than expected.
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