CHAPTER 54—MUSCULOSKELETAL DISEASES AND DISORDERS
DIAGNOSING MUSCULOSKELETAL DISEASE IN OLDER ADULTS
Musculoskeletal complaints are among the most common reasons that older adults seek medical attention. About 1 in 4 of all patients seen by primary care physicians presents with a musculoskeletal condition. Osteoarthritis (OA), whether based on radiographic findings, clinical symptoms, or self-report, is overwhelmingly prevalent in older persons. Depending upon the source of data and which joint is involved, OA is present in anywhere from 50% to 90% of older adults. In 1996, diseases of the musculoskeletal system and connective tissue accounted for about 7% of all Medicare spending.
The rheumatologic disorders can be broadly classified as those that present with predominantly musculoskeletal symptoms and those that present with symptoms suggesting a systemic illness. True joint disease (arthritis) is characterized by symptoms and physical examination findings localized to the joints. A patient’s history of joint swelling is strong evidence from the outset that true joint involvement is present. History of pain in a joint with motion or weight bearing is suggestive of arthritis. Further questioning about patterns of joint involvement, the presence of morning stiffness, stiffness after periods of inactivity, the effect of activity, and the effect on sleep can greatly narrow diagnostic possibilities.
Musculoskeletal symptoms that seem to be located in a joint are instead often due to a variety of disorders of periarticular tissues, muscles, nerves, and metabolism. These soft-tissue disorders include chronic postural strain, acute muscular and ligamentous strain, bursitis, and fibromyalgia plus conditions not directly related to joints, such as endocrinopathies and neuropathies. Pain complaints in soft-tissue disorders often involve anatomic regions, such as the shoulder girdle or a whole extremity, and rarely include a history of joint swelling; the patient commonly cannot clearly indicate which joint is involved.
When symptoms of pain and fatigue are generalized and not specifically referable to joints or classic bursal areas, differentiating between inflammatory and noninflammatory conditions is paramount. In the inflammatory disorders that may present with generalized aching and pain, there are usually historical and physical findings that lead to the correct diagnosis. The presence of rash, fever, stomatitis, dysphagia, Raynaud’s phenomenon, or true muscle weakness suggests one of the autoimmune rheumatologic disorders. The absence of such symptoms make generalized conditions such as fibromyalgia or regional conditions such as chronic postural strain or myofascial pain more likely.
Laboratory testing plays a small role in the diagnosis of rheumatologic diseases in older adults because of the lack of tests that are specific, the high background incidence of OA, and increased seroreactivity in later life, especially in women. Tests for erythrocyte sedimentation rate (ESR) and rheumatoid factor are neither sensitive nor specific. The antinuclear antibody test has such a high sensitivity in systemic lupus erythematosus (SLE) that a negative test essentially excludes it; however, a positive antinuclear antibody is of very low specificity. A few blood tests are specific. For example, either high titers of anti–double-stranded DNA antibodies or the presence of the anti-Sm antibody is specific for SLE, but unfortunately neither is sensitive. Most blood testing in rheumatologic conditions can, at best, only help confirm the clinical impression or provide prognostic data. Studies show that laboratory testing tends to be overused.
Clinicians who treat older adults have long understood the value of exercise. Exercise helps preserve muscle and bone mass, reverses the increased fat-to-muscle ratio associated with aging, and preserves physical function. In contrast, classic teaching in rheumatoid arthritis (RA) as recent as the mid-1980s was that exercise should be avoided and even that total bed rest was a mainstay treatment for severe flares. Conventional wisdom also held that weight bearing in OA would accelerate joint degeneration and that exercise in polymyositis would aggravate muscle inflammation. Increasingly, well-designed studies have disproved these beliefs and have now shown the value of exercise in the management of RA, OA, polymyositis, and SLE. Rather than worsening these disorders, exercise preserves function, reduces symptoms, and reduces sick days. Prescribed exercise must now be considered an essential part of the treatment of all the rheumatologic disorders.
The variety and number of conditions that present with musculoskeletal symptoms is impressive. This section describes the general approach to a patient with a regional musculoskeletal complaint and then discusses a selection of clinically common soft-tissue disorders.
Most musculoskeletal complaints in older adults are not caused by true arthritis but rather by disorders resulting from derangement of tendons, bursae, muscles, connective tissue, and nerves. Symptoms typically involve a region of the body rather than discrete joints. It makes sense to evaluate a new musculoskeletal complaint as likely soft-tissue rheumatism. The physical examination can begin with observation of the patient performing active range of motion of the affected region. Interpreting abnormal range of motion requires an understanding of the anatomy of the relevant muscles, tendons, bones, and nerves.
The shoulder, for example, is not a simple ball-in-socket joint, but an extremely mobile system of three bones (scapula, clavicle, and humerus) that is attached to the rest of the skeleton only at the sternoclavicular joint. The rest of the shoulder girdle floats and slides over the body and is controlled by a complex set of muscles and associated innervation. To analyze a painful shoulder, instruct the patient to abduct the shoulder from 0 degrees at the side through 90 degrees to 180 degrees, with hand above the head. Test shoulder internal and external rotation by having the patient put the backs of the hands on the sacrum and then the palms on the occiput. Depending on the result of these active range-of-motion tests, the examiner can further pinpoint the likely site of pathology by selectively moving the shoulder components for the patient. Passive motion is most informative when active motion has been demonstrated to be painful or limited. The glenohumeral joint can be isolated while the patient completely relaxes the shoulder; the examiner holds one hand over the upper scapula to prevent scapular motion and simultaneously slowly abducts, extends, flexes, and rotates the shoulder joint. True shoulder (glenohumeral) joint disease would be indicated should isolated passive joint motion be painful. In the case that active motion proved to be painless, then the examiner can first palpate key periarticular structures and then engage the patient with a series of selective resisted active movements that stress particular anatomic elements of the shoulder apparatus. Figure 54.1 shows an algorithm for analyzing the complaint of shoulder pain. A similar method can be applied to other regions of the musculoskeletal system.
When examination does not reveal arthritis, tendinitis, bursitis, or nerve impingement as the cause of regional pain, careful palpation may locate indurated, and sometimes crepitant, trigger points. Myofascial trigger points are distinct from the symmetrical multiple tender points of fibromyalgia in that palpation of trigger points reproduces the pain syndrome. Trigger points are most common over the upper back at upper or medial edges of a scapula. Similar trigger points can sometimes be discovered over the anterior chest, lower back, sacral, and iliac areas. The cause is poorly understood. Anesthetic injection into a trigger point can confirm the diagnosis. Treatment includes repeated ice application to the trigger points or injection with anesthetic or glucocorticoid, or both.
Fibromyalgia is a generalized pain syndrome that occurs at nearly all ages; prevalence rates of 2% to 10% are similar around the world, independently of nationality or ethnicity and cultural factors. Although there is no pathophysiologic explanation of the condition, the uniform worldwide incidence is persuasive that the condition is real. It was originally termed fibrositis in the early 20th century; more recent usage favors the term fibromyalgia, as there is no demonstrable inflammation in symptomatic tissues. A conceptual breakthrough was made nearly 30 years ago with seminal publications by Smythe and Moldofsky that demonstrated characteristic changes in sleep polysomnography in individuals who were defined by the classic “fibrositis” tender points (see Figure 54.2). Furthermore, it was found that electroencephalographic (EEG) changes and classic tender points could be induced by experimental disruption of deep sleep in normal volunteers. Researchers also learned that the EEG changes could be normalized and tender points could be resolved by aerobic exercise and by medications that tend to deepen deep sleep. Over the next 15 years, a multitude of symptoms were associated with fibromyalgia that tended to overlap with those of patients with irritable bowel syndrome and chronic fatigue syndrome. Some experts incorporated these symptoms as secondary criteria for diagnosis.
In 1990 the American College of Rheumatology (ACR) issued criteria for fibromyalgia diagnosis that were about 88% sensitive and 81% specific (see the caption for Figure 54.2). The criteria allow for the coexistence of fibromyalgia with other musculoskeletal disorders. With this approach, fibromyalgia is not simply a diagnosis of exclusion. No laboratory studies can help confirm the diagnosis. Despite the skepticism of many observers who believed fibromyalgia to be an artificial construct, research in the past decade has helped to develop an understanding of fibromyalgia as a condition of altered pain processing by the central nervous system. This research has paralleled advances in understanding the neurologic basis of pain itself. These advances have not yet led to new treatment, but there is ground for optimism.
The average age of fibromyalgia patients is around 45 years, and the majority are female. The condition seems to be a primary and persistent disorder that afflicts adults well into their 80s. Research indicates that the distress experienced by fibromyalgia patients diminishes with advancing age, suggesting that management in older adults may be less challenging. Mainstays of treatment have changed little in recent years. Reassurance that the condition is not life threatening and can be improved is indicated. Aerobic exercise is recommended, partly because of the original findings of Smythe and Moldofsky but also because of the deconditioning and muscle weakness seen in fibromyalgia. Analgesics give benefit; the role of narcotics is not yet well defined. Tramadol has been investigated and found to give benefit without serious adverse effects. Tricyclic antidepressants have long been used with benefit, but other antidepressants of different classes are also effective. Also, the muscle relaxant cyclobenzaprine and the benzodiazepine alprazolamOL have given benefit. Some patients find benefit from rotating medications every 6 months if tolerance seems to emerge. (See also “Persistent Pain”.)
Pain in the anterior shoulder with associated exquisite tenderness over the proximal biceps tendon and exacerbation with supination of the forearm (with elbow flexed to 90 degrees) against resistance (Yergason sign) is diagnostic of biceps tendinitis. Also, anterior flexion of the shoulder against resistance is likely to exacerbate the pain in biceps tendinitis. The condition is usually associated with repetitive motions but can be associated with bony impingement problems in the shoulder apparatus. Biceps tendinitis responds well to tendon sheath infiltration with glucocorticoid with or without anesthetic. Steroid iontophoresis can also be effective. Stretching and range-of-motion exercises are indicated during and following healing.
The shoulder rotator cuff is formed superiorly by a common tendinous insertion on the humeral greater tuberosity of the supraspinatus, infraspinatus, and teres minor muscles and inferiorly by the insertion of the subscapularis muscle on the lesser humeral tuberosity. Vascular supply to the upper portions of the rotator cuff is somewhat limited and easily compromised by impingement. Several bursae are associated with the rotator cuff and contribute to symptoms in rotator cuff problems. Rotator cuff disorders tend not to be as acute in older as in younger adults. A history of a recent acute event is not likely to be elicited, but a past episode of a fall with direct blow to the shoulder or falling with the arm outstretched may be recalled. Rotator cuff derangement can involve partial tear or degeneration or complete degenerative destruction. Although trauma is commonly an important factor, tissue ischemia from impingement and changes in bony relationships with advanced shoulder joint degeneration are more likely to be dominant factors in older patients. With complete loss of the rotator cuff, initiation of active abduction of the hanging arm is severely impaired. With partial tear or degeneration, only pain and giving way with the shoulder abducted to 90 degrees may be present. Management of rotator cuff degeneration should include identification of aggravating factors that can be avoided, especially sleeping with the arm outstretched. Initiation of tailored physical therapy to maintain shoulder range of motion is essential. Injection of a mixture of anesthetic and glucocorticoid into related bursal areas can be helpful in relieving pain and allowing progressive physical therapy to be successful. Surgery is an intervention of last resort in the treatment of rotator cuff disorders in older adults.
Intermittent pain in the shoulder, deltoid, and upper arm area in the absence of shoulder joint or associated musculotendinous structures should raise suspicion of cervical nerve impingement. The C5 level is most commonly involved. A cervical compression test (Spurling maneuver) can help identify cervical nerve impingement. In this maneuver the seated person tilts and turns the head slightly to the affected side. Steady vertical downward pressure on the top of the head is exerted by the examiner for 10 to 15 seconds. Reproduction of the symptoms on the affected side is a positive test. With more advanced impingement, sensory changes over the upper arm can be demonstrated on examination. Further evaluation would include cervical spine plain radiographs, including oblique views to optimally show the neuroforamina and detect bony impingement. Cervical disk disease can occur and might best be discovered with magnetic resonance imaging. Electrodiagnostic testing may also help sort out more obscure cases. Cervical traction twice daily at home, use of a cervical pillow, and avoidance of aggravating activities are the mainstays of conservative treatment. When muscle spasm is associated with cervical impingement, hot or cold applications plus injection of any identified trigger points can aid in the control of symptoms during recovery. Rarely, surgical intervention is needed for cervical nerve impingement.
Adhesive capsulitis (frozen shoulder syndrome) is an acute process of obscure cause that involves inflammation of the shoulder joint capsule. The condition can follow other shoulder disorders or injury. ESR may acutely increase. Unilateral shoulder involvement can help differentiate this condition from polymyalgia rheumatica. Shoulder pain and tenderness plus severely restricted active and passive range of motion are present. Early intervention with aggressive range-of-motion exercises combined with intra-articular glucocorticoids are important to preserve shoulder motion and reduce inflammation. Although not essential, shoulder arthrography with glucocorticoid and anesthetic injection at the time of arthrogram should be both diagnostic and therapeutic. In addition to intra-articular injection, percutaneous glucocorticoid injections anteriorly, posteriorly, and laterally into the glenohumeral joint capsule and shoulder bursal areas can also be effective. Adhesive capsulitis usually follows a course of several months that includes three phases: freezing, frozen, and thawing. With timely treatment, the outcome should be good, but physical therapy needs to extend well beyond the thawing phase.
Enlargement of the olecranon bursa with marked distension due to effusion with or without inflammation and surrounding cellulitis is common regardless of age. In younger adults occupational factors are often present, supporting the notion that olecranon bursitis can have an origin based in repetitive trauma. Olecranon bursitis is also commonly associated with RA and gout, with or without nodules in the former case and tophi in the latter. Infection of the bursa is also common, usually with staphylococci. Evaluation of an inflamed olecranon begins with sterile aspiration of fluid for cultures and cell count. The presence of surrounding cellulitis could be due to infection or acute gout; diagnostic aspiration of the bursa through affected skin mandates initiation of an antibiotic and continuation until culture results are in hand. Antibiotic selection should provide Staphylococcus aureus coverage, with modification that is based on culture results. Repeated aspiration during treatment may help recovery from infection. The course of recovery can be prolonged, with frequent relapses. The bursa often spontaneously drains, and complete healing of the cutaneous fistula may require many months. Olecranon bursitis associated with RA or gout is managed in accordance with the underlying disease once infection is excluded. Noninfectious olecranon bursitis suspected to be of traumatic origin should be treated with padding and avoidance of further trauma; aspiration and injection of the bursa could be considered. Close follow-up is indicated because olecranon bursae are so prone to spontaneous infection.
Entrapment of the median nerve where it passes through the carpal tunnel of the wrist is one of the most common nerve-entrapment syndromes in older adults. Symptoms of median nerve compression can occur with wrist synovitis due to RA, gout, or pseudogout. Hypothyroidism and diabetes mellitus are predisposing factors. Amyloidosis is an infrequent but well-known cause of carpal tunnel syndrome. The most common cause, however, is repetitive trauma. Carpal tunnel syndrome presents with nocturnal hand pain, tingling, and numbness involving the median nerve distribution in the hand. Pain during the day, even with radiation proximally to the shoulder, is occasionally seen and can confound diagnosis. In addition to the sensory deficits almost always present, atrophy of the thenar eminence can develop in longstanding median nerve compression. Evaluation should include inquiry into factors in the patient’s daily activities that could exacerbate carpal tunnel disease. Untreated or unrecognized hypothyroidism and diabetes should be tested for. A cock-up wrist splint, especially at night, can lessen symptoms. Some clinicians recommend isometric flexion exercises of metacarpal phalangeal joints and the affected wrist joint in which the tense flexor tendons act like a bowstring to stretch the transverse ligament overlying the carpal tunnel. Injection of glucocorticoids into the carpal tunnel, taking care not to inject the median nerve, can be of benefit and is highly recommended by some clinicians. Injection of the wrist joint when carpal tunnel syndrome is related to active wrist synovitis due to RA, gout, or pseudogout is usually quite effective. Surgical release of the transverse ligament can relieve symptoms when conservative measures fail.
Several bursae surround the hip joint and femoral trochanteric areas. Two bursa are of particular interest in soft-tissue rheumatism. The first is the bursa that directly overlies the greater femoral trochanter, and the second is deep to the gluteus maximus and posterior and slightly superior to the trochanter. Presenting symptoms of trochanteric bursitis include hip pain that is localized over the lateral proximal thigh. Pain on the affected side during sleep is usually present. The cause of trochanteric bursitis is not well understood. Significant predisposing factors may include local trauma, strain, and obesity. Treatment in elderly persons should include physical therapy, evaluation of transferring techniques to minimize excessive gluteal muscle stress, stretching exercises, and the use of a pillow positioned posterolaterally behind the involved side to discourage inadvertent resting on the affected bursa during sleep. Infiltration of the trochanteric areas with glucocorticoids is very helpful.
There are several bursae associated with the knee. In elderly persons the two most important are both associated with knee joint arthritis: the gastrocnemius and semimembranosus bursae in the popliteal fossa (see next section) and the anserine bursa anteromedially distal to the knee. The anserine bursa is located in relation to the insertion of the medial collateral ligament on the proximal tibia. Anserine bursitis presents with the complaint of knee pain that may bother the patient especially at night. Palpation over the area of the bursa should reveal marked local tenderness. Swelling, induration, or effusion may exist in association with anserine bursitis. Knee OA may be symptomatic as well. Cold applications may be of benefit. A pillow placed between the knees at night can lessen both nocturnal pain and recurrence in susceptible individuals. Injection of the bursa with a mixture of glucocorticoid and anesthetic is effective and can provide prompt relief.
A popliteal cyst (Baker cyst) may develop at any age. A symptomatic cyst can present with knee pain with pressure in the posterior knee; occasionally, a popliteal cyst can present with acute rupture. A popliteal cyst develops as an extension of the knee joint synovial space posteriorly into the gastrocnemius and semimembranosus bursae. Knee arthritis is almost always a precursor. Knee effusions in arthritis result in high resting intra-articular pressure that increases many-fold with knee flexion or with weight bearing. High knee synovial pressure tends to force fluid into one of the popliteal bursa. The communication between joint and bursa also tends to behave like a ball valve, with one-way movement of fluid from knee to bursa. This process leads to progressive popliteal cyst formation and enlargement, with eventual emergence of pain behind the knee. In addition to pain, the cyst can become a space-occupying lesion and can impede deep venous return from the lower leg.
Inspection for the presence of a popliteal cyst should be part of the routine knee examination in patients with known OA or who present with knee pain. Often a popliteal cyst is not distinctly palpable. Inspection of both popliteal fossae with the patient standing may reveal asymmetric fullness on one side. Hyperextension of the ankle while the knee is fully extended can accentuate the bulge of a popliteal cyst. Ultrasound examination of the popliteal fossa easily demonstrates the presence of a cyst. Though highly accurate, magnetic resonance imaging of the knee is rarely necessary to evaluate for a popliteal cyst.
A popliteal cyst can rupture spontaneously or with exertion. The result can be dramatic, with acute pain, swelling, warmth, and erythema of the lower leg that mimics all the signs of deep-vein thrombosis. In a few days bruising can surface in the lower leg and form a bruise below the lateral malleolus on the affected side (crescent sign). Occasionally, true deep-vein thrombosis can develop following acute popliteal cyst rupture. Venography or serial venous Doppler studies, or both, may be required to correctly interpret the course of popliteal cyst rupture. Glucocorticoid injection into the knee may be of benefit with acute cyst rupture, as presumably the same mechanisms that direct fluid from the knee to the popliteal cyst will carry the injected steroid into the area of the ruptured cyst. Similarly, knee arthrocentesis followed by glucocorticoid instillation for a symptomatic, but intact, popliteal cyst may reduce synovial fluid production and intra-articular pressure and give a few months’ improvement in popliteal symptoms. In the case of associated knee OA, a series of knee hyalin injections (see the next section) could ameliorate the factors driving popliteal cyst formation. Correction of the underlying knee disease that has led to development of the popliteal cyst is required to control cyst recurrence. Aspiration of the cyst itself, taking care to avoid the popliteal neurovascular bundle, with injection of glucocorticoid directly into the cyst is recommended by some clinicians.
OA, whether based on radiographic findings, clinical symptoms, or self-report, is overwhelmingly prevalent in older persons. Depending upon the source of data and which joint is involved, OA is present in anywhere from 50% to 90% of older adults. OA can be found in nearly 100% of adults aged 65 and over, and OA is the major cause of knee, hip, and joint pain, as well as back pain in older adults. Knee pain alone, according to data from NHANES III (the third National Health and Nutrition Examination Survey) affects more than 20% of adults aged 60 or over, with an incidence approaching 30% for those aged 80 and over. Sequential NHANES data suggests that the rising incidence of knee pain can be attributed to the worsening obesity and decreasing physical activity of Americans in recent decades.
OA is a degenerative disease of cartilage that correlates strongly with aging, yet pathologic changes in osteoarthritic cartilage are quite distinct from changes seen in normal aging cartilage. OA is also a heterogenous group of related joint disorders that have a variety of causes; these may be inborn, associated with metabolic disease, or due to joint malformation, joint trauma, or damage from other joint diseases. Distinct patterns of joint involvement are used to classify OA, ranging from isolated finger interphalangeal joint boney enlargement, to severe deterioration of weight-bearing joints, to isolated spinal involvement, and to generalized axial and peripheral joint degeneration. Primary OA appears to be genetically determined, with dominant expression in woman and recessive expression in men, and it tends to avoid wrists, elbows, shoulders, and ankles. Involvement of these joints with OA is suggestive of the presence of another disease or factor contributing to joint degeneration.
Underlying pathology in OA does not feature inflammation, though hypertrophy of synovium and accumulation of joint effusions is typical. Progressive changes in cartilage include poor chondrocyte function and death, altered cartilage composition with poor mechanical properties, cartilage surface fibrillation, and eventual gross cartilage destruction. Associated boney proliferation at the cartilage-bone interface leads to palpable and radiographically distinct osteophytes around affected joints.
Pain and reduced joint motion are the hallmarks of OA, with attendant ligamental instability and muscle atrophy. OA in weight-bearing joints is associated with gait abnormalities, and it increases the risk for falling and injury, contributing substantially to OA morbidity, especially in the oldest and most frail patients. Disability can be profound. The ACR diagnostic criteria for OA of the knee and hip are summarized in Table 54.1.
The management of OA usually begins with efforts to control pain. Rarely do analgesics alone accomplish pain control. By the time of physician evaluation for symptomatic OA, function has likely worsened because of muscle atrophy and joint motion limitation. These collateral changes put an affected joint at biomechanical disadvantage that both increases pain and predisposes the joint to ever more rapid deterioration. Early efforts to strengthen atrophied muscles related to the diseased joint and improve joint motion are critical. Analgesics play a role in allowing physical therapy to be used effectively in the long-term management of OA. Early referral to a physical therapist for evaluation and to define a set of exercises the patient can do daily at home is usually indicated. With OA of the weight-bearing joints, especially the knees, early remobilization and an ongoing walking exercise program may result in progressive functional improvement and reduction in pain rather than the often feared inevitable deterioration of the affected joints. Weight reduction can help reduce pain and improve function, especially if the lumbar spine or weight-bearing joints are involved. Joint injection with corticosteroids, joint injections with hyaluronic acid derivatives, and joint lavage can be of temporary benefit with low risk for toxicity. If there is a high interest in avoiding knee arthroplasty, a cartilage-preserving lateral tibial wedge osteotomy can be considered, provided there is isolated medial compartment knee osteoarthritis and the lateral knee compartment is intact. If conservative management proves to be inadequate with knee or hip disease, total arthroplasty is an excellent ultimate solution.
Recommendations about which analgesics to use for OA have changed over the past decade. Research shows that acetaminophen is often as effective as any of the nonsteroidal anti-inflammatory drugs (NSAIDs). Considerable gastrointestinal and renal toxicity can be associated with NSAID use in older adults. The ACR recommends that acetaminophen be the first analgesic chosen in treating OA. Similar recommendations have been issued by the American Geriatrics Society. Clinical studies over the past 2 years suggest an emerging consensus that NSAIDs may be slightly more effective in treating OA of the knee, especially when analgesia is still required after 3 to 6 months of treatment.
Controversy continues regarding possible kidney and liver damage from acetaminophen. There is no disagreement about the severe hepatic toxicity of acetaminophen overdose; however, hepatotoxicity is not seen when dosing guidelines are followed. Of course, with cognitively impaired elderly patients, there is always the possibility of inadvertent or accidental overdose of any prescribed medication. The possibility that chronic acetaminophen use contributes to renal insufficiency continues to intrigue investigators. Possibly because phenacetin was banned by the Food and Drug Administration more than 20 years ago because of the high risk of nephropathy, suspicions about acetaminophen (the active metabolite of phenacetin) persist. Nearly all studies of the renal effects of acetaminophen use have been retrospective and are impaired by numerous methodologic problems. The preponderance of data suggests that the risk of nephropathy from acetaminophen is quite low when it is used in modest doses by those without preexisting kidney disease. Acetaminophen, given under physician supervision, is still the analgesic of choice for patients with existing renal insufficiency, according to the National Kidney Foundation recommendations.
If acetaminophen is initially ineffective, nonacetylated salicylates such as salsalate or magnesium choline salicylate, which have lower gastrointestinal toxicity than most older NSAIDs, can be given. The selective COX-2 inhibitors are more expensive. COX-2 inhibitors have the same risk of unwanted renal effects as the other NSAIDs. They may also be associated with increased risk of myocardial infarction. The COX-2 inhibitors are further discussed in the section on RA.
Hyaluronic acid is a major constituent of synovial fluid and is a major contributor to synovial fluid viscosity and a contributor to cartilage elasticity. Hyaluronic acid and hyaluronan polymers were approved for intra-articular injection for OA of the knee in 1997. This viscosupplementation therapy is given in a series of weekly knee joint injections, five for hyaluronic acid and three for hyaluronan polymers. The benefits of these preparations typically last for 6 months, which is substantially longer than for corticosteroid injection.
Glucosamine and chondroitin sulfate are components of glucosaminoglycan molecules that are important in maintaining mechanical properties of connective tissue and cartilage. When given orally, these compounds are absorbed and incorporated into cartilage. Both have been studied separately as treatments for OA, with evidence of benefit. In OA of the knee, the effectiveness of glucosamine is equivalent to that of ibuprofen, with less gastrointestinal toxicity. The therapeutic benefit of chondroitin sulfate does not become apparent for several weeks after it is started, and improvement lasts for several weeks after it is stopped. Long-term studies will be needed before chondroitin sulfate can be considered a disease-modifying drug for OA. Glucosamine and chondroitin sulfate are available in combination as nutriceuticals. Though both compounds are nontoxic, the dosage and bioavailability of these nutriceuticals are not established; therefore, the benefit seen in therapeutic trials cannot be predicted with these over-the-counter preparations.
Gout is perhaps the oldest recognized form of arthritis; it was unmistakably described in Hippocrates, and Sydenham’s clinical description of his own experience of gout in the late 17th century can hardly be improved upon today. Through the 19th century, the classification of arthritis had rheumatic fever as a distinct form of arthritis, and other forms of joint disease were considered to be subtypes of gout. Hence, terms like rheumatoid gout were used for the disease now called rheumatoid arthritis. These views prevailed until about 150 years ago when the relationship of classic gout with high levels of uric acid in blood was recognized. Proof of intra-articular monosodium urate crystals as the specific cause of acute gout was not established until the early 1960s.
Gout often presents as acute monarthritis, usually of the first metatarsal phalangeal joint, mid-foot, or ankle. With subsequent attacks, the knee, elbow, or wrist can be involved. Later in the course of untreated disease, attacks tend to be less intense and to last longer, and they may feature simultaneous involvement of more than one joint. Late in untreated disease, chronic low-grade inflammation in multiple joints appears and tophi (gross subcutaneous urate deposits on extensor surfaces) develop. In this late phase of untreated gout, the condition can be mistaken for nodular RA, with the tophi being mistaken for rheumatoid nodules. This can be a sad error, as gout and RA do not occur together, and the two conditions are treated differently. Thus, a strong case is made for microscopic evaluation of samples of joint fluid in the initial evaluation of chronic polyarticular, as well as acute monarticular, arthritis.
With rare exceptions, the clinical emergence of gout is preceded by a period of asymptomatic hyperuricemia. However, hyperuricemia is not uniformly present at the time of an acute gout attack, nor does the presence of hyperuricemia confirm a diagnosis of gout. Acute attacks can be precipitated by trauma, acute nonarticular illness requiring hospitalization, dehydration (acute gout is particularly common postoperatively), or medications that can perturb serum uric acid levels.
A diagnosis of gout is most directly and unequivocally established by observing the presence of strongly negatively birefringent needle-shaped crystals in a sample of joint fluid. Needle-shaped urate crystals can often be seen by ordinary or dark field microscopy of joint fluid, but confirmation of negative birefringence requires the use of a polarizing microscope equipped with a compensator plate. Many laboratories and most rheumatologists have access to such a microscope. This type of microscope is essential in diagnosing pseudogout, described in the next section.
The treatment of gout is biphasic. The acute episode is best managed with a short course of an NSAID. The choice of the NSAID is not critical, as the risk of gastrointestinal toxicity is less likely to emerge during the 10 to 21 days needed for an acute attack to respond. Drugs such as allopurinol or probenecid, which can acutely lower uric acid levels, should not be used in the management of acute gout, as premature lowering of uric acid level will paradoxically intensify and prolong an acute gout attack.
Once the acute attack is resolved, attention can be turned to correcting the underlying problem of urate deposition. Urate accumulation in body tissues can be due to uric acid overproduction in the body, reduced renal elimination, or a combination of both. Ninety percent of chronic hyperuricemia is a consequence of reduced renal excretion that is due to renal disease or drugs, especially diuretics. Uric acid overproduction in older adults is seen in disorders with increased tissue turnover, such as lymphoproliferative disease, chronic hemolytic anemia, and psoriasis, as well as rare genetic enzymatic defects.
Drugs, for example probenecid, that promote renal uric acid excretion can correct hyperuricemia in young adults who have normal kidney function. In older adults, reduced kidney function renders uricosuric drugs less effective. The most effective treatment for uric acid reduction is allopurinol, which acts by blocking the formation of uric acid. Allopurinol dose can be adjusted upward from a starting dosage of 100 mg daily, increasing the daily dose by 100 mg at 2- to 4-week intervals until serum uric acid levels are 5 or below. Because of the high likelihood of decreased kidney function with aging, somewhat lower allopurinol doses may be adequate in older patients to depress uric acid to the desired therapeutic level.
During treatment to lower uric acid levels, the risk of recurrent acute gout attacks is raised. Prophylaxis against acute attacks is advisable for 3 to 6 months while treatment to lower uric acid is introduced and optimized. Although NSAIDs could be used for prophylaxis, the risk of gastrointestinal toxicity with chronic use must be considered. Colchicine can be effective for prophylaxis in older adults at a reduced dosage of 0.6 mg daily. This low dose is well tolerated and does not have an associated risk of gastrointestinal ulceration. Colchicine should be avoided in individuals with hepatic disease or advanced renal insufficiency and is contraindicated if both hepatic and renal diseases are present.
Radiographically evident deposition of calcium pyrophosphate dihydrate (CPPD) crystals in articular tissue is markedly related to aging and can be seen in up to 50% of adults aged 90 and over. CPPD crystals can be found in synovial fluid and are associated with several clinical syndromes. CPPD crystals can cause attacks of acute monarthritis, most commonly the knee, wrist, and shoulder, termed pseudogout because of the resemblance to acute (urate) gout. CPPD deposition can occur simultaneously in multiple joints and be responsible for chronic polyarticular synovitis reminiscent of RA. Radiographic chondrocalcinosis with or without CPPD crystals in the synovial fluid can also be present in joints with OA without any evidence of inflammation. The coexistence of CPPD crystals and OA is not surprising, as both conditions are common in older adults; however, controversy persists regarding the relationship of the two disorders. Differentiation of CPPD deposition arthropathy from urate gout and RA is important, as the treatment approaches are different.
Acute pseudogout attacks can be treated with a limited course of oral colchicineOLor an NSAID in a manner similar to the treatment for acute urate gout. Similarly, intra-articular corticosteroids will halt an attack in patients for whom an NSAID is contraindicated. Parenteral corticosteroids have been shown to be effective for acute pseudogout when NSAIDs and intra-articular corticosteroid injections are both contraindicated. Given once with possible repeat in 1 to 2 days, triamcinolone acetonide 60 mg IM, betamethasone 7 mg IM, or methylprednisolone 125 mg IV have all proven to be safe and effective. Although a single intravenous dose of colchicine of 1 to 2 mg is long acting and can be effective in treating acute pseudogout, the risk of tissue necrosis with accidental extravasation and of bone-marrow suppression in older adults with renal or hepatic impairment suggests this should be considered very carefully in individual cases. Recurrent attacks of pseudogout can be prevented by the use of prophylactic oral colchicine. Any combination of oral and IV colchicine is absolutely contraindicated.
Polymyalgia rheumatica (PMR) is a distinct syndrome that occurs in older adults, as early as age 50 but predominantly after age 60. The onset tends to be insidious, with corresponding delays in diagnosis. The classic symptom of PMR is remarkable proximal limb girdle stiffness and aching pain upon arising in the morning. ESR is so often markedly elevated that a high ESR is one of the essential diagnostic criteria. The syndrome may be accompanied by fatigue, low-grade fever, weight loss, and variable expression of synovitis of proximal joints of the upper, more than lower, extremities. Studies of PMR in recent years have confirmed the presence of synovitis identical to that seen in RA, with synovial thickening, effusions, and lymphocytic synovial infiltration. PMR can progress to chronic polyarthritis that fulfills criteria for RA. Of more immediate clinical importance is the common coexistence of PMR with giant cell arteritis (GCA), a more serious, potentially life-threatening disease. This relationship is discussed in the next section. Even with uncomplicated PMR, treatment with corticosteroids is associated with significant iatrogenic long-term morbidity, including diabetes mellitus, osteoporotic fracture, muscle atrophy, hypertension, glaucoma, and acceleration of cataracts and skin atrophy.
The cause of PMR is unknown. Studies for infectious agents responsible for triggering the syndrome have been inconclusive. Type II HLA gene associations have been found, but associations differ from those for RA.
The standard treatment of PMR is oral prednisone beginning at 15 mg daily. Dramatic improvement is so much to be expected that some have proposed that low-dose corticosteroid responsiveness confirms the diagnosis of PMR. ESR normalization corresponds to initial symptomatic improvement. Prednisone dose can be tapered over succeeding months on the basis of control of symptoms. PMR often runs a course of 2 to 3 years, and many patients are able to discontinue prednisone by then. Unfortunately, mean time to the first adverse event on corticosteroid therapy for PMR is about 1.6 years. Occasional patients with PMR respond to NSAIDs. Though long-term prednisone has significant toxicity, prednisone may be safer in older adults than NSAIDs, provided the prednisone dose can be minimized and parallel efforts are made to protect bone mass. In a randomized trial of methylprednisolone acetate, a dosage of 120 mg IM every 3 to 4 weeks has been found to control PMR with fewer fractures, less weight gain, and lower cumulative dose than a daily oral prednisone regimen.
Giant cell arteritis (GCA) is the most common form of vasculitis to affect older adults. This form of vasculitis predominantly affects proximal branches of the aorta. Therefore, inflammatory and ischemic manifestations are mostly seen in the head and upper extremities. Occasionally, gross inflammation with tender, nodular swelling and erythema of the temporal arteries can be seen. In the absence of gross findings, symptoms of temporal headache, jaw and tongue claudication, and sudden vision loss may be seen. Diagnosis can be confirmed by biopsy of a temporal artery, thus the often-used synonym temporal arteritis. ACR criteria for the diagnosis of GCA are available on the ACR Web site (http://www.rheumatology.org/publications/classification). The recognition of GCA is often preceded by several months of a nonspecific systemic illness that includes weight loss, fever, and muscle aching that is indistinguishable from PMR. GCA can also present with sudden blindness with no prior systemic illness or with upper-extremity limb claudication. Other manifestations can include stroke, ischemic necrosis of tongue or scalp, or, rarely, myocardial infarction. Aortic aneurysm, predominantly thoracic, is a late manifestation of GCA even when previously appropriately treated. The incidence of aneurysm in GCA is about 10%, with thoracic and abdominal aneurysm discovery 5.9 and 2.5 years, respectively, after GCA diagnosis.
The cause of GCA is unknown. Infectious agents have long been suspected, but none has yet been confirmed as causative. Recent studies of biopsy material revealed the presence of parvovirus B19 DNA. In another study, serum IgM antibodies (implying recent infection or reinfection) against type I parainfluenza virus correlated very well with biopsy-positive GCA.
The diagnosis of GCA may require a high index of suspicion combined with the finding of an otherwise unexplained elevated ESR above 40 mm/hour. Combined elevation of ESR and C-reactive protein is more specific (97%) than elevated ESR alone for biopsy-positive GCA. Because of the risk of sudden blindness, most clinicians would start high-dose oral prednisone as soon as the possibility of GCA is seriously considered, and then proceed to biopsy. Administration of prednisone does not change arterial histology for weeks. Diagnosis can sometimes even be established or reestablished after a few years of prednisone treatment. Arterial involvement is patchy, and diagnostic histologic changes can be missed by biopsy. This oversight can be minimized by biopsy of the symptomatic side and by obtaining a several centimeters length of artery. Multiple longitudinal sections as well as cross-sections of artery should be examined by a pathologist. Still, on occasion biopsies are negative in cases where suspicion remains high. Biopsy of the opposite side is recommended by some; however, in a study of bilateral temporal artery biopsy in 150 patients suspected of GCA, results from the two sides were found to agree in 97% of the cases.
Since 25% of cases of GCA are associated with PMR, there is a longstanding controversy as to which patients with PMR should undergo temporal artery biopsy. There are no clear data to guide decision making in this situation. One reasonable criterion would be to obtain temporal artery biopsies in cases of PMR in which there are symptoms or physical findings suggestive of arteritis (ie, temporal headache; visual changes; tongue, jaw, or limb claudication; neck or chest pain; or neurologic changes suggestive of central nervous system ischemia). The temporal artery can also be involved with other forms of systemic vasculitis. Vasculitides other than GCA should be considered whenever the temporal artery biopsy shows necrotizing vasculitis but an absence of giant cells.
The treatment of GCA requires high-dose prednisone initially. No other treatment has been so clearly proven to be effective. Clinicians differ on the definition of high dose, with some recommending starting dosages as high as 120 mg daily. There are no data that show dosages above 40 mg daily to be more effective. Older adults are highly susceptible to corticosteroid toxicity, and toxicity increases markedly with total dose. The use of higher doses should be individualized and considered when there is resistance to initial treatment or disease is unusually severe. Response is confirmed when ESR falls rapidly over the first month of therapy. Tapering of the steroid should begin at the rate of 10% to 20% of the total dose per month as soon as the ESR is normalized. Published studies of methotrexate as a steroid-sparing agent have not consistently proven methotrexate to be effective.
Late-onset RA appears to be clinically different from the same disease with onset earlier in life. The condition in the older adult is more likely to be of rapid onset, involve fewer and more proximal joints, and to be rheumatoid-factor negative. Nodules are less likely and joint destruction may be less severe. Overall prognosis may be better than with earlier onset, seropositive, nodular, erosive disease. Nevertheless, RA is a chronic disease that persists indefinitely, with high risk for progressive joint damage and functional impairment, and more recent reviews confirm that late-onset RA is still a serious disease. Criteria to aid in the diagnosis of RA are listed in Table 54.2.
Treatment is almost always indicated, and therapeutic options have increased since 1998 with the introduction of a variety of entirely new drugs for the management of RA. In more severe cases, consultation with a rheumatologist is indicated.
NSAIDs are often recommended as first-line medications for symptom control in RA. The older nonselective NSAIDs, such as ibuprofen, naproxen, diclofenac, and several others, nonspecifically inhibit both cyclooxygenase isoenzymes. Celecoxib was approved in late 1998 as the first of a new class of NSAIDs, the selective cyclooxygenase-2 enzyme (COX-2) inhibitors. Rofecoxib was approved in mid-1999 for OA and pain and more recently for RA. Valdecoxib was the third COX-2 inhibitor to become available for RA and was approved for marketing in late 2001.
The hope for the selective COX-2 inhibitors was that they would be substantially free of antiplatelet effects, gastric toxicity, and renal toxicity. Clinical studies have confirmed that the incidence of serious gastric toxicity was about half that of nonselective COX NSAIDs. However, if COX-2 inhibitors are used concomitantly with mini-dose aspirin, the risk of gastric toxicity becomes similar to that of older NSAIDs. Renal toxicity, unfortunately, has proved to be as serious with the COX-2 inhibitors as with older NSAIDs.
In 2004 reports emerged that there was an increased risk of myocardial infarction during the first 6 weeks after starting rofecoxib. Subsequent studies of rofecoxib for prevention of adenomatous polyps confirmed an increased risk of stroke and myocardial infarction with long-term use of rofecoxib versus placebo. These reports led to the withdrawal of rofecoxib from the market in late 2004. Valdecoxib was voluntarily withdrawn from the market by the manufacturer in early 2005. Celecoxib is still marketed. The mechanism of increased cardiovascular adverse effects from COX-2 inhibitors is uncertain. The lack of inhibition of platelet function could be a partial explanation, as older NSAIDs at least reversibly inhibit platelet aggregation.
Certainly, NSAIDs can no longer be considered first-line therapy for arthritis or other chronic, painful conditions. Alternatives to old NSAIDs and selective COX-2 inhibitors might include the relatively selective COX-2 inhibitors: nabumetone, etodolac, and meloxicam. Nabumetone and etodolac were introduced prior to celecoxib, and meloxicam was introduced in 2004. These three agents have generally lower serious gastric adverse effects than older NSAIDs and have less renal toxicity than either older NSAIDs or the selective COX-2 inhibitors. At this time, they are not known to cause an increased risk of stroke and myocardial infarction with long-term use. Therapy with a low-dose corticosteroid such as prednisone may be a preferable option, provided doses can be limited to 5 mg daily and precautions are taken to preserve bone density. The nonacetylated salicylate, salsalate, has minimal gastric mucosal toxicity yet has preserved anti-inflammatory activity.
RA is recognized as a lifelong systemic disease associated with progressive joint and extra-articular organ involvement that leads to functional decline and shortened longevity. Mere symptomatic treatment is no longer considered appropriate. Disease-modifying drugs should be considered for treating all cases of RA. Longitudinal studies have confirmed the preservation of function when disease-modifying drugs are instituted early and maintained over the long term.
Parenteral gold, penicillamine, azathioprine, and cyclophosphamide use has markedly declined in the past decade because of the availability of safer effective drugs. Methotrexate has been approved for use in RA for more than a decade and has become established as the disease-modifying agent of choice. When given daily, methotrexate can cause hepatic injury, with cirrhosis and end-stage liver failure. Low-dose, weekly, oral pulse therapy dramatically reduces the risk of hepatic toxicity, provided ethanol intake is completely avoided. Methotrexate can be used in combination with other immunosuppressive agents to yield proven additive or synergistic benefit. Since 1991, more than 100 cases of lymphoproliferative disease have been reported in patients with RA who are under treatment with methotrexate. Usually, the lesion is extranodal non-Hodgkin’s lymphoma, and remission is often seen when methotrexate is stopped. At least one population-defined study did not find excess cancer in RA patients treated with methotrexate in comparison with RA patients who never received methotrexate.
Randomized controlled studies have now confirmed that minocycline 100 mg twice daily is effective in treating RA with minimal toxicity. MinocyclineOL would be a good choice for mild disease or when there is a need to start therapy even when the initial phase of diagnostic uncertainty has not passed. Similarly, hydroxychloroquine is well tolerated and does not require blood-test monitoring for toxicity. When dosages are limited to 5 mg/kg/day, the risk of retinal toxicity is very low. Weekly oral methotrexate is well tolerated by the older adult and can be added if hydroxychloroquine alone is ineffective. Sulfasalazine (only the enteric coated tablets are approved for RA) is more effective than hydroxychloroquine but requires divided daily dosing, has a high incidence of gastrointestinal intolerance, and cannot be given in the presence of sulfa allergy.
Cyclosporine is approved for use in severe RA alone or in combination with methotrexate. Toxicity remains a concern, and the role of cyclosporine in treating RA is still evolving.
Leflunomide, approved in 1998, is the first disease-modifying antirheumatic drug introduced for over a decade and is the first such drug approved both for symptomatic improvement of RA and to prevent radiographic progression in joint damage. It has relatively fast onset of action (about 4 weeks) in comparison with older disease-modifying drugs.
Etanercept was approved in late 1998 for use in treating RA that had failed at least one other disease-modifying agent. Etanercept is a tumor necrosis factor receptor blocker produced by recombinant DNA techniques. It is given in twice-weekly subcutaneous injections and is expensive. Clinical benefit is seen within 1 to 12 weeks, and it must be given indefinitely to maintain benefit. The major risk of etanercept is the development of serious granulomatous infections (see discussion below under infliximab). Headache is a common, less severe adverse effect.
Infliximab was approved in late 1999 in combination with methotrexate for treatment of RA. Infliximab is a monoclonal antibody that prevents interaction of tumor necrosis factor alpha with its receptor. Infliximab must be given by intravenous infusion. Clinical trials show marked initial response to a single infusion, but continued response to bimonthly infusions requires concomitant administration of oral methotrexate.
Both etanercept (0.07%) and infliximab (0.24%) are associated with an increased incidence of granulomatous infections with organisms such as tuberculosis, atypical mycobacterium, yeast, listeria, and nocardia. Other adverse effects associated with infliximab include systemic postinfusion reactions of fever, chills, headache, chest pain, and dyspnea. Antibody formation is common but reduced by the concurrent use of methotrexate.
Adalimumab was approved in 2002. It is similar to infliximab except that this therapeutic antibody is entirely human. Adalimumab is given by subcutaneous injection every other week and does not require concomitant methotrexate therapy. Serious infections similar to those seen with infliximab have been reported, but data about relative incidence are not available.
Anakinra was introduced in 2001 as a recombinant form of the human interleukin-1 receptor antagonist IL-1Ra. Anakinra is administered as daily subcutaneous injections. Infections during anakinra therapy are mostly bacterial respiratory tract infections with no opportunistic infections.
Though thought of as a disease in younger women with a higher prevalence among black women, SLE can present in later life. SLE is a multisystem disorder that can have a wide variety of presentations and predominant organ system involvement at any age. SLE is diagnosed with high specificity when any four or more of eleven criteria are documented singly or together at any time during the patient’s life (for a detailed description of the ACR criteria, see http://rheumatology.org/publications/classification).
Criteria include malar rash, photosensitivity, stomatitis, nonerosive arthritis, serositis (pleurisy or pericarditis), seizure, nephropathy (urinary casts or heavy proteinuria), cytopenias (leukopenia, hemolytic anemia, or thrombocytopenia), positive antinuclear antibody, and any one of other immunologic abnormalities (anti-double stranded DNA, anti-SM, or false positive test for syphilis). Fever, Raynaud’s phenomenon, alopecia, migraine, antiphospholipid syndrome, and Sjögren’s syndrome are also often seen in SLE.
It is not surprising that patterns of organ involvement in SLE are different in older adults. Numerous studies suggest that late-onset SLE affects women and men more equally (3:1 in older adults versus 10:1 in young adults); relatively more white than black older adults are affected. Late-onset SLE is less likely to present with rash, arthritis, Raynaud’s phenomenon, nephropathy, and the involvement of the central nervous system and more likely to present with serositis, Sjögren’s syndrome, and positive rheumatoid factor. In older adults, SLE onset may be more insidious, involve fewer organ systems, and have fewer relapses. As nephropathy and central nervous system involvement are related to mortality in younger women, late-onset lupus has been sometimes thought of as a milder disease. Despite the impression of milder disease in older adults, immunosuppressive and cytotoxic medications are required as often in managing late-onset SLE.
Hormonal factors may be partly responsible for the differences between early- and late-onset SLE. Estrogens are suspected of being an aggravating factor in young women. Studies of the administration of postmenopausal estrogen for 2 years or more in women is associated with a fivefold increase in SLE risk. The increased risk is somewhat lower if estrogen is combined with a progestational agent. In a population-based study, SLE in women was found to be associated with a doubled overall incidence of cancer.
The treatment of SLE in older adults is similar to the treatment given in early-onset disease. Corticosteroids are less well tolerated by the older adult and should be reserved as much as possible for organ- or life-threatening SLE flares. Hydroxychloroquine has been shown to be of benefit in SLE skin involvement and to reduce the overall number of disease relapses in younger adults. Hydroxychloroquine is well tolerated and has few serious adverse effects in dosages of 5 mg/kg/day or less. Dapsone, azathioprine, and weekly oral methotrexate are used by some clinicians as alternatives to corticosteroids or as corticosteroid-sparing agents. Monthly intravenous pulse cyclophosphamide is reserved for severe or life-threatening disease.
Sjögren’s syndrome with xerostomia and keratoconjunctivitis sicca has been long recognized as occasionally complicating RA. The incidence of Sjögren’s syndrome in other connective-tissue diseases is also increased. Dry eye and dry mouth symptoms without confirmation of Sjögren’s syndrome occur in up to 40% of older adults who do not have a connective-tissue disease, and these symptoms are undoubtedly contributed to by many of the medications often prescribed to older adults. The treatment of sicca symptoms and uncomplicated Sjögren’s syndrome is targeted to the symptoms and includes artificial tears and artificial saliva and ophthalmologic and dental preventive care. Pilocarpine 5 mg three times a day can help stimulate saliva flow.
Sjögren’s disease (SD) is a systemic, multiorgan chronic disease that features lymphocytic infiltration of exocrine glands throughout the body, including lacrimal, salivary, respiratory tree, intestinal tract, pancreatic, hepatic, renal, and vaginal glands. In addition, cutaneous vasculitis and central nervous system involvement are often seen. The involvement of salivary and lacrimal glands is responsible for the sicca symptoms seen in Sjögren’s syndrome that is associated with other connective-tissue diseases. The peak onset of SD is in mid-life to early late life.
There is no single diagnostic test for SD. Unexplained interstitial lung disease, renal impairment, hepatic dysfunction, esophageal dysfunction, malabsorption, or central nervous system disease resembling multiple sclerosis should raise the suspicion of SD. Antinuclear, anti-SSA, and anti-SSB antibodies are usually present. Rheumatoid factor and a variety of autoantibodies against gastric parietal cells, mitochondria, smooth muscle, and thyroid are often seen. An ophthalmologic examination can confirm the presence of keratoconjunctivitis, and biopsy of a lip or lacrimal gland can confirm the presence of characteristic lymphocytic infiltration. Biopsy of a rash can verify the presence of cutaneous vasculitis.
Symptomatic and preventive treatment is indicated for sicca symptoms, as described above. Trial therapy with hydroxychloroquine may help stabilize disease activity, as in SLE. Dapsone may be effective for cutaneous vasculitis. Corticosteroids and other cytotoxic drugs should be reserved for organ- or life-threatening disease.
Polymyositis (PM) is a heterogeneous group of inflammatory diseases of striated muscle that are not unique to older adults; however, late-onset PM is evaluated and treated somewhat differently in older adults. The onset of PM is often insidious. The cardinal symptom is muscle weakness, most marked in proximal muscle groups. Muscle tenderness is usually not prominent. Exercise tolerance is reduced, and an inability to perform simple tasks such as reaching above the head or ascending stairs may be present. Other system involvement is common in PM and reminiscent of other connective-tissue diseases, including rash, arthritis, esophageal dysmotility, and Raynaud’s phenomenon. Cardiac involvement is not rare and usually presents with dysrhythmias. Rash may involve the eyelids (heliotrope) or the nose and malar areas, or be more generalized. Rash with dorsal thickening over the interphalangeal joints (Gottron’s papules) are distinctly different from the dorsal phalangeal rash of systemic lupus that spares the interphalangeal joints. When rash is present, PM is referred to as dermatomyositis (DM).
In contrast to childhood PM, adult-onset PM affects women more often than men, and blacks more often than whites. Also, esophageal involvement and respiratory failure complicated with bacterial pneumonia are more likely in older PM patients. Up to 50% of cases of late-onset PM, and especially DM, are associated with underlying malignancy. No one cancer type seems most strongly associated: Colon, lung, breast, prostate, uterus, and ovary are all well represented with PM and DM. Ovarian cancer is the most commonly associated gynecologic cancer underlying PM and DM. Mortality in adult PM and DM is usually associated with esophageal disease, respiratory failure with bacterial pneumonia, and malignancy.
Serum levels of muscle enzymes are usually markedly elevated in PM. Electromyography will reveal changes consistent with myositis, provided affected muscle is tested. Paraspinal muscle involvement is typical and should be included in the muscles tested. The diagnosis is confirmed with muscle biopsy that reveals inflammatory cellular infiltrates. The diagnosis of PM or DM in older adults entails a search for underlying malignancy. Minimum evaluation would include chest radiography and colon examination. In women, a pelvic examination and imaging plus mammography is included; in men, a prostate examination and prostate-specific antigen testing.
An important histologic and clinical subtype of PM is inclusion-body myositis. Rimmed vacuoles and an accumulation of amyloid in muscle fibers are seen on muscle biopsy. Inclusion-body myositis predominantly affects men and is more likely to involve distal muscle groups including the volar forearm flexor and ankle dorsi flexor muscles. The onset and progression is slower than in PM. Inclusion-body myositis is also thought to be relatively resistant to anti-inflammatory therapy.
Remission of PM and DM after treatment of an underlying malignancy is seen. Therapy should also generally be directed at the inflammatory process itself. Corticosteroids are almost always the first drug of choice. Prednisone at 1 mg/kg/day is a typical starting dosage. Some clinicians advocate three daily intravenous doses of methylprednisolone 1000 mg initially for severe disease. In the absence of prospective data, this high-dose regimen should be individualized. Prednisone can be tapered after an initial phase of improvement of muscle strength and normalization of muscle enzyme levels. Rates of tapering of 10% to 20% of the total dose per month are typical. Methotrexate, given parenterally, in a weekly pulse regimen can be combined with corticosteroids. Somewhat higher methotrexate doses than those used in treating RA are given by some clinicians, up to 50 mg weekly. Methotrexate may also have a steroid-sparing effect in long-term therapy. Weekly oral methotrexate is effective in managing refractory skin manifestations of DM. Azathioprine may also have a steroid-sparing effect, but it is not as well accepted in the treatment of PM. Supervised exercise over 6-week and 6-month study periods has proven to be beneficial in PM, improving function without aggravating the underlying disease.
■ Agudelo CA, Wise CM. Crystal-associated arthritis in the elderly. Rheum Dis Clin North Am. 2000;26(3):527–546.
This is an accessible review of gout, calcium pyrophosphate deposition arthropathy, and basic calcium phosphate deposition (hydroxyapatite) arthropathy. Each of these disorders has a variety of clinical manifestations, and each requires a different approach for managing acute presentation and chronic symptoms.
■ American Geriatrics Society Panel on Exercise and Osteoarthritis. Exercise prescription for older adults with osteoarthritis pain: consensus practice recommendations. J Am Geriatr Soc. 2001;49(6):808–823.
This is a thorough review of osteoarthritis management that emphasizes nonpharmacologic approaches. It also represents American Geriatrics Society practice guidelines for osteoarthritis. The entire article can be accessed at the society Web site (http://www.americangeriatrics.org).
■ Evans JM, Hunder GG. Polymyalgia rheumatica and giant cell arteritis. Rheum Dis Clin North Am. 2000;26(3):493–515.
Much clinical lore and mystique surround polymyalgia rheumatica and giant cell arteritis and their interrelationship. This review provides a concise summary of what is scientifically known about these conditions and their management. Much of this body of knowledge derives from the extensive population-based experience of the Mayo Clinic.
■ Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998; 41(5):778–799.
As arthritis is the leading cause of disability in adults aged 65 years old or older, this report is important. Arthritis prevalence is 45% (9.9% with activity limitation) in adults aged 65 to 74, 55% (13.1% with limitation) aged 75 to 84, and 57.1% (18.5% with limitation) aged 85 and over. Prevalence data for the full spectrum of rheumatologic disorders are provided in this review.
■ Mishra N, Kammer GM. Clinical expression of autoimmune diseases in older adults. Clin Geriatr Med. 1998;14(3):515–542.
This review includes discussion of late-onset systemic lupus erythematosus, Sjögren?s syndrome or disease, and the inflammatory myopathies. It covers the epidemiology, pathology, evaluation, and treatment of each of the three disorders. Extensive references are included.
■ Rexrode KM, Buring JE, Glynn RJ, et al. Analgesic use and renal function in men. JAMA. 2001;286(3):315–321.
This report is a large prospective study of chronic analgesic use by more than 11,000 males; analgesics included both acetaminophen and nonsteroidal anti-inflammatory drugs. The authors conclude that their “findings provide assurance to clinicians and patients that moderate analgesic use is unlikely to contribute to increased risk of renal dysfunction among individuals without a history of renal impairment.”
■ Sewell KL. Rheumatoid arthritis in older adults. Clin Geriatr Med. 1998;14(3):475–494.
Despite the impression that late-onset rheumatoid arthritis is a milder disease, it still must be considered a lifelong multisystem disease with serious morbidity and increased mortality. Disease-modifying drugs are required as often in late-onset rheumatoid arthritis as in early-onset disease, and older adults are more vulnerable to the toxicity of these agents. This article is a comprehensive review of late-onset rheumatoid arthritis; however, it predates release of the newest agents: leflunomide, etanercept, infliximab, anakinra, and adalimumab.
■ Solomon DH, Schneeweiss S, Glynn RJ, et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation. 2004;109(17):2068–2073.
For several years, a series of reports raised increasing concerns about thromboembolic adverse effects of cyclooxygenase-2 (COX-2) inhibitors. The authors analyzed large databases of Medicare beneficiaries who were enrolled in comprehensive medication benefits programs. The COX-2 inhibitor rofecoxib was found to be associated with an increased risk of acute myocardial infarction in comparison with celecoxib, another COX-2 inhibitor, or with nonselective nonsteroidal anti-inflammatory medications. This will be an important area of scrutiny because of the high rates of cardiovascular and musculoskeletal disease in elderly patients and resulting widespread use of nonsteroidal anti-inflammatory medications in this age group.
John W. Rachow, PhD, MD