Evaluation of Joint and Other Musculoskeletal Symptoms

Precise anatomic localization of pain is the first task of the physician caring for a patient presenting with joint pain, while also evaluating stiffness, redness, warmth, or swelling in the absence of trauma. It is important to distinguish pain that is truly articular from periarticular pain. Causes of localized periarticular pain include bursitis, tendonitis, and carpal tunnel syndrome, whereas fibromyalgia, polymyalgia rheumatica, and polymyositis all can cause diffuse periarticular pain.

The number of involved joints and presence or absence of symmetry are criteria for further diagnosis of articular pain (Figs. 32-1 and 32-2). Monoarticular (one joint) or oligoarticular (several joints) arthritides can be caused by conditions such as osteoarthritis (OA), gout, pseudogout, or septic arthritis. Asymmetric polyarthritis occurs in ankylosing spondylitis, psoriatic arthritis, Reiter’s disease, and spondyloarthropathies. Symmetric arthritis, meaning that the same joint is affected on the contralateral side but not necessarily to the same degree, is characteristic of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren’s syndrome, polymyositis, and scleroderma. Fibromyalgia, reflex sympathetic dystrophy, and predominantly psychological factors must be considered when pain is diffuse, not relatable to specific anatomic structures, or described in vague terms. (See also Chapter 30.)

Figure 32-1 Evaluation of monoarticular or pauciarticular symptoms. ANA, Antinuclear antibodies; CBC, complete blood cell count; ESR, erythrocyte sedimentation rate; JRA, juvenile rheumatoid arthritis; LFTs, liver function tests; PMNs, polymorphonuclear (leukocyte) neutrophils; PT, prothrombin time; PTT, partial thromboplastin time; RA, rheumatoid arthritis; RF, rheumatoid factor; SLE, systemic lupus erythematosus; WBCs, white blood cells.

(From American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for the initial evaluation of the adult patient with acute musculoskeletal symptoms. Arthritis Rheum 1996;39:1.)

Figure 32-2 Evaluation of polyarticular symptoms. ANA, Antinuclear antibodies; CBC, complete blood cell count; ESR, erythrocyte sedimentation rate; RF, rheumatoid factor.

(From American College of Rheumatology Ad Hoc Committee on Clinical Guidelines: Guidelines for the initial evaluation of the adult patient with acute musculoskeletal symptoms. Arthritis Rheum 1996;39:1.)

Other differentiating criteria include the correlation with activity or rest and the character of the pain. Mechanical causes tend to be more directly related to the joint’s activity than inflammatory conditions. Neuropathies tend to cause burning or prickling sensations, whereas arthritides often cause an aching pain. The presence of joint stiffness after a period of inactivity might also aid in diagnosis; RA is characterized by morning stiffness lasting 30 to 60 minutes or longer, whereas OA-related morning stiffness lasts a shorter period, typically less than 30 minutes, but stiffness might also occur during the day. In neurologic conditions such as Parkinson’s disease, stiffness might be relatively constant. Vascular pain, such as intermittent claudication, is felt with activity, relieved quickly by rest, and described as a “deep, aching” sensation.

Constitutional symptoms such as fatigue, weakness, malaise, and weight changes are common chief complaints heard in a primary care office practice and often associated symptoms of specific rheumatic diseases. The patient’s functional ability, occupational history, and activities requiring repetitive joint movement, as well as the ergonomics of such activities, should also be considered routinely in initial and serial evaluations. How are the symptoms affecting the patient’s ability to perform self-care activities of daily living (ADLs) such as bathing, dressing, and eating? Is the patient able to do instrumental activities of daily living (IADLs) such as buying groceries, cooking, using the telephone, and opening jars? Rheumatic disease can have a devastating effect on quality of life for both the patient and the family, with serious psychosocial and economic consequences. Therefore the physician should address effects on occupational, recreational, and sexual activities in the context of family and other support systems.

Physical Examination

A thorough physical examination should be performed on all patients presenting with joint pain, including examination of asymptomatic joints and other organ systems that might be involved. Joints should be examined for swelling, tenderness, deformity, instability, and limitation of motion. Comparisons with the patient’s contralateral side can be made in all these parameters, as well as with the physician’s joints as a control. Instability can be tested by moving adjacent bones in the direction opposite to normal movement and observing for greater-than-normal motion. Serial grip strength measurements can be made by asking the patient to squeeze a blood pressure (BP) cuff inflated to 20 mm Hg and recording the maximal grip force in millimeters of mercury. Signs of systemic disease include fever; weight loss; oral or nasal ulcerations; liver, spleen, or lymph node enlargement; neurologic abnormalities; rashes; subcutaneous nodules; eye iritis; conjunctivitis or scleritis; and pericardial or pulmonary rubs. Because of circadian changes in patients with RA, serial comparisons of the physical examination are more accurate if the time of day is also recorded. Using skeleton diagrams of joint involvement facilitates the recording of a comprehensive joint examination (Fig. 32-3).

Figure 32-3 Skeleton diagram for recording joint examination findings.

(From Polley HF, Hunder GG. Rheumatologic Interviewing and Physical Examination of the Joints, 2nd ed. Philadelphia, Saunders, 1978.)

Myalgias can be caused by localized trauma or overuse, systemic infection, metabolic disorder, or primary muscle disease. Multiple tender sites in an otherwise healthy patient suggest fibromyalgia. An elevated creatine kinase (CK) level with proximal weakness may be caused by an inflammatory myopathy.

Rheumatic and other musculoskeletal problems are properly diagnosed by careful history and physical examination rather than by just ordering many laboratory tests, the results of which might actually confuse diagnosis. Laboratory tests and radiologic imaging help confirm a presumptive clinical diagnosis made from a careful history and physical examination.

Pathogenesis of Rheumatic and Other Musculoskeletal Diseases

As with most disease, research into the causes of rheumatologic and musculoskeletal diseases shows that the cause for each disease is actually multifactorial. Further identification of these factors will help the family physician and rheumatologist modify the course of disease and eventually perhaps even prevent them.

Genetic factors have been identified for several arthritides. Presence of the human leukocyte antigen (HLA) system’s HLA-DR4 antigen is associated with increased incidence and severity of RA. The HLA-B27 antigen is found in a higher percentage in patients with ankylosing spondylitis and other spondyloarthropathies than in the general population. Other factors are apparently involved, however, because its presence or absence neither guarantees nor excludes development of arthritis testing for these antigens if not routinely performed. A National Institutes of Health (NIH) study found that genetic factors contributed 39% to 65% of OA variance. About 80% of patients with chondrodysplasias were found to have a type II collagen gene mutation likely linking these findings to OA (Prockop, 1998).

Inborn errors of metabolism are well known to cause diseases such as gout, in which uric acid is overproduced or underexcreted by the kidneys. Poorly controlled metabolic diseases such as diabetes or hemochromatosis might lead to arthropathies. Mechanical or traumatic factors cause OA in soccer players but not in long-distance runners, indicating that the type and direction of joint stress might be more important than the stress itself. Adduction moment is associated with OA disease severity. Obesity is also an identified factor in OA of the knee, possibly because of metabolic influences as well as mechanical forces (Eaton, 2004).

Infectious agents such as parvovirus B19, human immunodeficiency virus (HIV), Neisseria gonorrhoeae, Borrelia burgdorferi (Lyme disease), and streptococci (rheumatic fever) are all well-known causes of arthritides. Some speculate that dietary factors might contribute to autoimmune syndromes, and fasting or a vegan diet (or both) can lead to improvement in RA (Kjeldsen-Kragh et al., 1991; McDougall et al., 2002). The imbalance of omega-6 and omega-3 fatty acids in the standard American diet (a ratio of 30:1, as opposed to the ratio of 1:2 that is thought to have been present in Paleolithic diets) is also postulated to contribute to a more inflammatory state. Omega-6 fatty acids are preferentially converted to more inflammatory prostaglandins such as arachidonic acid, whereas omega-3 fatty acids can be converted into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which contribute to anti-inflammatory series-3 prostaglandin production (Fig. 32-4). Omega-3 fatty acids are useful in RA, showing a decrease in use of nonsteroidal anti-inflammatory drugs (NSAIDs) and decreased levels of pain (Oh, 2005).

Figure 32-4 Influence of omega-6 fatty acids and omega-3 fatty acids on inflammation.

(From Rakel R. Integrative Medicine. Philadelphia, Saunders-Elsevier, 2007.)

Other medical systems, such as traditional Chinese medicine (TCM), may have completely different explanations for the changes seen in rheumatologic conditions. Although a conventional practitioner may not be aware of these, it is helpful to know about complementary modalities that may be beneficial (e.g., acupuncture helping patients with OA and fibromyalgia).

Laboratory Studies

A complete cell count (CBC) with differential, urinalysis, and renal and liver function tests should be performed if asymptomatic rheumatic disease is suspected. Importantly, the frequency of abnormal laboratory results increases with increasing age in the normal population, even in the absence of disease, including common tests such as erythrocyte sedimentation rate (ESR), uric acid, antinuclear antibodies (ANAs), and rheumatoid factor (RF). Thus, arthritis panels can confuse the situation and should not be performed routinely. For example, only 80% of patients with RA have a positive RF. RF is a serum autoantibody against immunoglobulin G (IgG). Up to 4% of the healthy population has a positive RF, which is also frequently positive in patients with chronic obstructive pulmonary disease (COPD), viral hepatitis, and sarcoidosis, and can also be positive in malignancy, and primary biliary cirrhosis and other autoimmune diseases. The higher the RF titer, however, the more likely it is caused by RA. ANA test results are positive in 95% of patients with lupus, and the test is often used to screen for SLE, but the result is also positive in 5% of the normal population. Drug use, age, and other factors might also cause a positive ANA test result. ANA titer also does not correlate exactly with changes in disease activity, so it should not be ordered in the absence of systemic symptoms. A patient with a positive ANA without clinical features is unlikely to have SLE. However, higher titers of ANA make it more likely that the result is related to lupus or another rheumatologic disorder.

Laboratory studies can be helpful in monitoring disease activity and drug toxicity as well as in establishing a diagnosis. CBC can detect anemia secondary to the chronic disease of RA or from NSAID-induced gastrointestinal (GI) blood loss. Patients with SLE can have hemolytic anemia, thrombocytopenia, or lymphopenia. Urinalysis can detect renal disease secondary to SLE, NSAIDs, or disease-modifying antirheumatic drugs (DMARDs) being used to treat RA. An elevated uric acid level can suggest gout. Acute-phase reactants such as ESR and C-reactive protein (CRP) can be useful to monitor disease activity but are nonspecific; they can also be negative in the presence of active disease. Patients with temporal arteritis and polymyalgia rheumatica almost always have a greatly elevated ESR. With weakness or muscle pain, CK level should be measured and arthralgias with abnormal liver enzyme levels followed up with hepatitis viral serologies.

Other tests, such as HLA-B27, antineutrophil cytoplasmic antibody, Lyme or parvovirus serologies, myositis-specific antibodies (anti–Jo-1), and antiphospholipid antibodies, are useful only when the clinical suspicion is high for spondyloarthropathies, Wegener’s granulomatosis, Lyme or parvovirus infection, inflammatory myositis, or antiphospholipid antibody syndrome, respectively (American College of Rheumatology, 1996).

Synovial Fluid Analysis

Synovial fluid analysis can be helpful in evaluating a febrile patient with an acute joint to rule out septic arthritis or acute monoarthritis. Synovial fluid should be analyzed for white blood cell (WBC) count differential, cultured, and tested with polarized light microscopy for crystals. Purulent synovial fluid with greater than 90% polymorphonuclear leukocytes (PMNs), low viscosity, and turbid clarity can be caused by infection or crystal arthropathy (gout or pseudogout). Urate crystals are needle-shaped and negatively birefringent; calcium pyrophosphate dihydrate crystals are rhomboidal and weakly positively birefringent. Noninflammatory fluids generally have a clear appearance, normal viscosity, fewer than 2000 WBCs/mm³, and less than 75% PMNs (Table 32-1).

Table 32-1 Interpretation of Synovial Fluid Cell Count

Leukocyte Count (WBCs/mm3)	Interpretation
<200	Normal synovial fluid
<2000	Noninflammatory fluid
>2000	Inflammatory fluid
2000-20,000	Mild inflammation (e.g., SLE)
20,000-50,000	Moderate inflammation (e.g., RA, reactive arthritis)
50,000	Severe inflammation (e.g., sepsis, gout)
>100,000	Sepsis, until proved otherwise

WBCs, White blood cells; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis.

From Towheed TE, Hochberg MC. Acute monoarthritis: a practical approach to assessment and treatment. Am Fam Physician 1996;54:2239.

Synovial fluid analysis should always be performed on freshly obtained fluid. A simple bedside test is to attempt to read newsprint through the synovial fluid; newsprint can be read through noninflammatory fluid (Fig. 32-5). Traditional tests on synovial fluid that are of limited or no value include measurement of glucose, lactate, and protein levels; subjective determination of viscosity; mucin clot test (examining the friability of the precipitate formed by mixing synovial fluid with dilute acetic acid); and immunologic tests. When looking for crystals and infection, direct examination, Gram stain, culture, and WBC count with differential are the only tests worth performing on synovial fluid. Inflammatory synovial fluid must be considered secondary to infection until proved otherwise by culture. The presence of crystals in the joint does not exclude the possibility of joint infection.

Figure 32-5 Synovial effusions. A, Normal or edema fluid is clear, pale yellow, or colorless. Print is easily read through the tube. B, Fluid from noninflammatory joint disease is yellow and clear. C, An inflammatory effusion is cloudy and yellow. Print may be blurred or completely obliterated, depending on the number of leukocytes. The effusion is translucent. D, A purulent effusion from septic arthritis contains a dense clump that does not even allow light through the many leukocytes. E, Hemorrhagic fluid is red. The supernatant may be darker yellow-brown (xanthochromic). A traumatic tap is less uniform and often has blood streaks.

(From Schumacher HR. Synovial fluid analysis and synovial biopsy. In Kelley WN, Harris ED, Ruddy S, et al [eds]. Textbook of Rheumatology, 5th ed, vol 1. Philadelphia, Saunders, 1997, pp 609-625.)

Synovial biopsy can facilitate a diagnosis in some settings. Arthroscopy has greatly simplified the acquisition of synovial tissue. This might be helpful in the diagnosis of granulomatous disease or infiltrative processes such as lymphoma, metastatic disease, or amyloidosis (Klippel, 2001).

Rheumatic Diseases

Osteoarthritis

Key Points

• Osteoarthritis affects 20% of the U.S. population; 44% of OA patients are not active.

• Primary and secondary OA must be differentiated.

• NSAIDs, not COX-2 inhibitors, are still the pharmacologic treatment of choice for OA.

Osteoarthritis, also known as “degenerative joint disease,” is the most common form of arthritis and causes more work disability in the United States (17%) than any other disease. Arthritis affects 20% of the U.S. population, about half of whom primarily have OA. Long thought to result from “wear and tear,” OA is now known to have genetic, traumatic, metabolic, and developmental causes, which complicates prevention and treatment. OA is found radiographically in almost all 75-year-old patients, most of whom are asymptomatic. OA occurs about equally in men and women ages 45 to 55 but after 55 is more common in women (CDC, 2005). Most OA patients are not seriously affected and are asymptomatic. Others, however, require joint replacement surgery because of its severity.

Although OA is considered a noninflammatory type of arthritis affecting primarily the cartilage, it actually involves active biochemical disease processes as well as mechanical forces that affect the entire synovial joint. An OA variant affecting primarily the hands runs in families and is inflammatory. Women are more prone to this inflammatory variant of OA of the hands that causes Heberden’s nodes (in distal interphalangeal [DIP] joints) and Bouchard’s nodes (in proximal interphalangeal [PIP] joints). The articular cartilage may not even be involved, with the disease process centered more on subchondral bone turnover (Peterson et al., 1998). Quadriceps muscle weakness might precede the onset of knee OA, indicating the importance of biomechanical factors (Slemenda et al., 1997).

Osteoarthritis can be separated into primary (idiopathic), hereditary (resulting from collagen gene defects), and secondary. Secondary OA results from previous cartilage damage. Occupations causing repetitive joint trauma predispose a patient to OA. Episodic trauma, congenital anatomic abnormalities (slipped capital femoral epiphyses, congenital hip dysplasias), neuropathies, and endocrine-metabolic causes (obesity, hemochromatosis, Wilson’s disease, CPPD disease, Paget’s disease, acromegaly) all might lead to OA. Inflammatory arthritides such as RA, infections, or gout damage cartilage and are often followed by the development of OA.

Occupational kneelers (e.g., shipyard workers, miners, carpet or floor layers) have a significantly higher incidence of knee OA than control groups of clerical workers (Maetzel et al., 1997). However, repetitive sports activities such as long-distance running are unlikely to cause OA in the absence of joint injury or antecedent joint abnormality (Panush and Lane, 1994). More than 44% of patients with diagnosed OA are inactive (Gordon et al., 1998). Low-impact activity in normal joints is not associated with OA, but high-intensity and high-impact activity resulting in injury is associated with OA. Mechanical risk factors might affect the initiation more than the progression of OA. Most mild OA does not progress to severe joint damage. Mild OA might be a different disease than severe OA, which depends on processes other than early OA.

Clinical Findings

Most OA is asymptomatic, an incidental finding on radiographs performed for other reasons. No treatment or further evaluation is indicated for asymptomatic OA. Early symptomatic OA is characterized by local pain of gradual onset exacerbated by using the involved joint. Pain typically worsens as the day progresses and is relieved by rest. There is less than 30 minutes of localized morning stiffness and no constitutional or systemic symptoms, and the gel phenomenon (stiffness after periods of rest and inactivity) resolves within several minutes of activity. Damp, cool, rainy weather often exacerbates symptoms because of changes in intra-articular pressure associated with changes in barometric pressure. Patients with OA of the knees might complain of buckling or instability, especially when descending stairs. OA of the hip can manifest as pain radiating from the groin and down the anterior thigh. OA of the neck might be felt in the neck, back, or upper extremities, causing pain, weakness, or numbness. As OA progresses, pain can become continuous, including at night.

Primary OA can be divided into three classifications: generalized OA, large-joint OA, and erosive OA. Generalized OA involves five or more joints, most often the DIP joints of the hand (Herberden’s nodes), the PIP joints of the hand (Bouchard’s nodes), the first carpometacarpal joint, the first MTP joint of the feet, and the knee, hip, and spine. There is a significant familial component. Large-joint OA of the knees and hips might occur as part of generalized OA or alone. OA of the knees often occurs in the medial and patellofemoral compartments. OA of the hips can be characterized in two subsets, central and superior poles. Central or medial involvement of the hip joint space occurs in the setting of generalized OA, is usually bilateral, and is seen in women more than men. Most hip OA is superior pole, usually unilateral, seen more in men, and occurs without other joint involvement. As many as 40% to 90% of cases of adult hip OA might arise from subtle developmental abnormalities of the hip, including acetabular dysplasia, developmental (formerly “congenital”) hip dislocation, Legg-Calvé-Perthes disease, and slipped capital femoral epiphysis (Brandt and Slemenda, 2004).

A rare form of primary OA known as erosive OA involves the hand’s PIP and DIP joints equally, with significant inflammation. Other joints are often not involved, although 15% of erosive OA cases might subsequently evolve into seropositive RA (Kujala et al., 1995).

Physical Findings

Physical findings of OA typically include joint swelling, tenderness, crepitus, and enlargements at joint margins, causing deformity. The location of pain should be precisely localized as to whether it is truly articular or periarticular; if pain is located in the joint, an inflammatory or infectious cause should be ruled out first. Patients might have reduced ROM or, in severe cases, joint instability, resulting in excess motion or locking because of loose cartilage fragments. Warmth and soft tissue swelling because of joint effusion might be present, but a markedly swollen, hot, erythematous joint suggests a septic or microcrystalline disease rather than OA.

Laboratory Studies

Clinical study criteria for OA classification are helpful as a means to standardize the diagnosis (see eTables 32-2 and 32-3 online). Although the diagnosis of OA can almost always be made by history and physical examination, definitive diagnosis can be helped by synovial fluid analysis, radiography, and normal ESR, ANA, and RF during symptomatic periods. Synovial fluid analysis of large-joint effusions can be used to exclude other processes. Joint effusions in OA typically show leukocyte counts lower than 1000 WBCs/mm³, predominantly lymphocytes (Table 32-2). Serum tests might be misleading because ESR rises with age and 20% of healthy older adults have positive RF levels. A greatly elevated ESR suggests a process other than OA. Although many have been identified, biochemical markers of OA are not generally useful to the practicing clinician at this time.

Table 32-2 Criteria for Classification of Idiopathic Osteoarthritis (OA) of Knee

Clinical and Laboratory	Clinical and Radiographic	Clinical∗
Knee pain plus at least five of nine:	Knee pain plus at least one of three:	Knee pain plus at least three of six:
Age >50 years Stiffness <30 minutes Crepitus Bony tenderness Bony enlargement No palpable warmth ESR <40 mm/hr RF <1:40 SFOA	Age >50 years Stiffness <30 minutes Crepitus plus Osteophytes	Age >50 years Stiffness <30 minutes Crepitus Bony tenderness Bony enlargement No palpable warmth
92% sensitive	91% sensitive	95% sensitive
75% specific	86% specific	69% specific

ESR, Erythrocyte sedimentation rate (Westergren); RF, rheumatoid factor; SFOA, synovial fluid signs of OA (clear, viscous, or white blood cell count <2000/mm³).

∗ Alternative for the clinical category would be four of six, which is 84% sensitive and 89% specific.

From Altman R, Asch E, Bloch G, et al. Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum 1986;29:1039-1049, with permission of the American College of Rheumatology.

Imaging Studies

Radiographs are generally the first-line confirmation of the presence of OA. Treatment should not be based solely on radiographic abnormalities, however, given the frequency of asymptomatic joints demonstrating radiographic OA changes. OA changes include osteophyte formation, asymmetric joint space narrowing (defined as <3 mm on a weight-bearing knee), and subchondral bone sclerosis (Figs. 32-6 and 32-7). Later in the disease process, subchondral cysts with sclerotic walls might develop. Periarticular osteoporosis and marginal erosions suggest RA or some other inflammatory arthritis rather than OA. Patients with OA involving atypical joints (MCP joints, wrists, elbows, shoulders, or ankles) should be evaluated for an underlying disorder such as CPPD or hemochromatosis.

Figure 32-6 Osteoarthritis in the hand.

(From Resnick D, Yu JS, Sartoris D. Imaging. In Kelley WN Harris ED, Ruddy S, et al [eds]. Textbook of Rheumatology, 5th ed, vol 1. Philadelphia, Saunders, 1997, pp 626-686.)

Figure 32-7 Osteoarthritis in the knee. A, Anteroposterior radiograph of knee showing asymmetric joint narrowing. B, Anteroposterior radiograph showing osteophyte formation in knee (arrow).

(From Resnick D, Yu JS, Sartoris D. Imaging. In Kelley WN Harris ED, Ruddy S, et al [eds]. Textbook of Rheumatology, 5th ed, vol 1. Philadelphia, Saunders, 1997, pp 626-686.)

Treatment

Treatment of OA includes pharmacologic therapy, nonpharmacologic therapy, and surgery. Before initiating treatment, a definitive diagnosis of OA must be made by careful history and physical examination. No currently available treatment has been shown to alter the natural history of the disease. Therefore, the goal of management of OA is primarily to relieve pain, stiffness, and swelling. The physician seeks to reduce limitation of motion and disability without causing iatrogenic side effects. Patients and their families must also be educated about the disease and their treatment options (Box 32-1).

Box 32-1 Options in the Management of Patients with Osteoarthritis

From Hochberg MC. Osteoarthritis: clinical features and treatment. In Klippel JH (ed). Primer on the Rheumatic Diseases, 12th ed. Atlanta, Arthritis Foundation, 2001, pp 293-295.

Nonpharmacologic Therapy

Patient education and self-management programs

Social support through telephone contact

Physical and occupational therapy

Range of motion (ROM) and strengthening exercises

Aerobic conditioning

Weight loss

Assistive devices for ambulation and activities of daily living

Pharmacologic Therapy

Oral nonopioid analgesics (e.g., acetaminophen)

Topical analgesics (e.g., capsaicin cream)

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Intra-articular steroid injections

Opioid analgesics

Surgical Therapy

Closed tidal joint lavage

Arthroscopic debridement and joint lavage

Osteotomy

Total joint arthroplasty

Nonpharmacologic therapy includes rest during pain episodes, exercise, weight control, avoidance of trauma, patient and family education, and assistive devices. The patient’s ability to perform both self-care ADLs and IADLs requiring higher functioning (e.g., shopping, driving, writing) should be assessed. Physical and occupational therapists can provide great benefit by offering an exercise program and assistive devices to maintain independence and minimize symptoms (Fransen et al., 2001). Patients benefit from the use of canes, walkers, bathtub and toilet wall bars, and dressing sticks for socks and from the other methods of joint protection and symptom relief, such as heat massage. Rest is important for patients with acute pain. Otherwise, helpful exercise programs include swimming, other aerobic conditioning, and walking (van Baar et al., 1999). Weight control and weight reduction have also been shown to improve symptoms (Messier et al., 2004).

First-line pharmacologic therapies for symptom control include acetaminophen, up to 1000 mg four times daily in the absence of liver disease, and traditional NSAIDs, beginning with ibuprofen. Because few RCTs studied differences in efficacy of NSAIDs, the initial choice is empiric. Therefore, relative safety, patient adherence, and cost should determine selection. Risk factors for upper GI bleeding with NSAIDS include age over 65, history of peptic ulcer disease or upper GI bleeding, concurrent use of oral corticosteroids and anticoagulants, and possibly smoking and alcohol consumption. Evidence suggests that NSAIDs are superior to acetaminophen for improving knee and hip pain from OA. No significant difference in overall safety was found, although patients taking NSAIDs were more likely to experience an adverse GI event (Towhead et al., 2006). Capsaicin (Zostrix) topical cream four times daily, formerly a first-line agent, now has been shown to have minimal benefit, especially when considering side effects that impair compliance (Mason et al., 2004). Combination therapy (NSAIDs with analgesics) may also be helpful. The addition of tramadol (Ultram, 200 mg/day) in patients responding to 1000 mg/day of naproxen has been shown to allow significant reduction (by half) in the naproxen dose needed without compromising pain relief (Schnitzer et al., 1999).

Misoprostol (Cytotec) was the first U.S. Food and Drug Administration (FDA)–approved drug for GI protection when used with NSAIDs, although higher doses of famotidine (Pepcid), nizatidine (Axid), and omeprazole (Prilosec) also decrease the risk of NSAID-induced gastric ulcers. Currently, NSAIDs plus a PPI such as omeprazole remains the treatment of choice for prevention of NSAID-induced gastric ulcers. Opioid analgesics and limited intra-articular corticosteroid injections (up to 4 injections per joint per year) are the remaining traditional choices. Opiates should generally be avoided for long-term use but might be helpful for acute exacerbations. It is unclear whether the risks of long-term NSAID use outweigh the addiction potential of chronic opiate use.

Intra-articular glucocorticoids are often used and are particularly useful in patients with contraindications or continued pain despite NSAIDs. This modality is postulated to work by decreasing cartilage catabolism and osteophyte formation. A meta-analysis found that patients receiving intra-articular steroid injections for OA of the knee were twice as likely to have short-term improvement as controls (Arroll et al., 2004). Data on injection of the hip and knee joint show the most promise, but efficacy at other sites is less certain. Aseptic technique should be used to prevent iatrogenic complications of infection. Patients should be counseled on postinjection complications such as bleeding, infection, skin hypopigmentation, fat necrosis, and steroid flare.

Because OA is a common incurable disease that causes pain, many other treatments, including dietary supplements and other alternative therapies, have been tried for centuries. Balanced hormone therapy, copper bracelets, bee venom, vitamins, herbs, homeopathic remedies, and certain types of foods are promoted as effective treatments or cures for OA. Family physicians should be aware of proven and unproven remedies used by their patients. One therapy shown to be efficacious is glucosamine sulfate.

Glucosamine and chondroitin sulfates both stimulate the production of proteoglycan in cartilage and inhibit its breakdown. Over-the-counter formulations vary in the amount of glucosamine (made from crab shells) and chondroitin (processed from cow cartilage). Research has shown that patients have moderately benefited from glucosamine and chondroitin supplements over 3 years with less knee joint space narrowing on radiography, significant reduction of symptoms, and no adverse effects (Richy et al., 2003). The major studies of glucosamine used two different formulations of the supplement, which yielded different results, the Rotta brand and non-Rotta formulations. A 2005 Cochrane review found that a non-Rotta preparation failed to show benefit in pain and function, whereas the Rotta preparation showed that glucosamine was superior to placebo in the treatment of pain and functional impairment resulting from symptomatic OA. Studies for chondroitin are less convincing, with no consistent improvement in pain or functional status (AAFP, 2006). The safest daily intake is 1500 mg/day of glucosamine and 1200 mg/day of chondroitin. Most capsules containing both minerals are also formulated with manganese, theorized to assist in proteoglycan metabolism but not studied (Richy et al., 2003).

A meta-analysis of 11 studies found that S-adenosylmethionine (SAMe) was as effective as NSAIDs at reducing pain and functional limitations, with a somewhat better adverse effect profile (Soeken et al., 2002).

A Cochrane review of herbal therapies for OA found two studies demonstrating that avocado-soybean unsaponifiables showed beneficial effects on function, pain, intake of NSAIDs, and global evaluation (Little et al., 2004). Another beneficial intervention is transcutaneous electrical nerve stimulation (TENS) for OA of the knee; electrical stimulation has been shown to improve knee OA moderately by 25% and cervical OA by 12% (Osiri et al., 2004).

Studies comparing acupuncture with a sham control found greater improvement in those receiving the actual treatment (Berman et al., 2004; Ezzo et al., 2001; Vas et al., 2004). A meta-analysis found that acupuncture was more effective than placebo in pain reduction in peripheral OA (Kwon et al., 2006). Two studies found that therapeutic touch, an energy modality, showed benefit in OA (Gordon et al., 1998). Although previously cited as beneficial for OA secondary to antioxidants, the literature reports an increased risk of cardiovascular disease with vitamins C and E (Alkhenizan and Palda, 2003).

Other, less traditional therapies have received much media attention but not shown effectiveness. Cycles of three or more weekly intra-articular injections of hyaluronic acid (viscous substance in synovial fluid that lubricates and protects joints) have been used, with partial success (Abramowicz, 1998a). Hyaluronate sodium (Hyalgan) and hylan G-F 20 (Synvisc) are FDA approved for OA of the knee. Onset of pain relief can take several weeks and can last for 6 months or longer. Meta-analyses of hyaluronic acid have shown minimal effectiveness versus placebo. The cost/benefit ratio favors therapies other than joint injection (Lo et al., 2003).

Other largely unproven therapies include doxycycline, diathermy (deep heat using ultrasound), iontophoresis with dexamethasone, and intra-articular therapeutic gene therapy before joint replacement. Although diathermy and iontophoresis are widely used and have widespread anecdotal reports of subjective relief of pain, there is no definitive proof of benefit.

KEY TREATMENT

Treatment of osteoarthritis begins with nonpharmacologic modalities, including weight loss (Messier et al., 2004), physical therapy (Fransen et al., 2001), exercise (van Baar et al, 1999), and orthotics if needed (SOR: A).

Acetaminophen and NSAIDs are both first-line pharmacotherapy for pain associated with OA, although NSAIDs appear to be more effective (Towhead et al., 2006) (SOR: A).

Intra-articular glucocorticoids show short-term improvement in pain associated with OA of the hip and knee (Arroll et al., 2004) (SOR: B).

Treatments such as Synvisc (Lo et al., 2003), glucosamine (Richy et al., 2003), and acupuncture (Kwon et al., 2006) are often used for OA relief before surgical measures (SOR: B).

Rheumatoid Arthritis

Key Points

• Rheumatoid arthritis affects women 3:1 over men, with 70% having an insidious onset.

• Symmetric synovitis with morning stiffness longer than 1 hour is the hallmark of RA.

• Constitutional symptoms are common in patients with RA.

Rheumatoid arthritis is a chronic inflammatory systemic disease in which cellular and autoimmune mechanisms result in destruction of tissues, primarily the synovium. Genetic predisposition appears to be important, but a specific inciting infectious agent or other cause has still not been found. RA manifestations vary from very mild, self-limited disease to multiorgan destruction and early death. Increasing knowledge of the modulating factors in disease progression is transforming the treatment of RA. Without treatment, the normally fluctuating disease course results in progressive joint destruction. Patients with active, polyarticular, RF-positive RA have more than a 70% chance of developing joint damage or erosion within 2 years (Fuchs et al., 1989). Because RA is relatively uncommon compared with OA and is now treated quite differently, the family physician must be able to make the correct diagnosis and initiate disease-modifying therapy early, before joint destruction.

Epidemiology

Rheumatoid arthritis affects women more frequently than men (about 3:1 ratio) and occurs in all age groups but has a peak incidence between 20 and 50 years. Prevalence is 1% to 2% of adults, ranging from 0.3% of the population younger than 35 to about 10% of those older than 65. There is a higher concordance of RA in monozygotic twins than in dizygotic twins because of gender differences and differences in major histocompatibility complex (MHC) class II gene products (HLA-DR). Combinations of different genes most likely predispose patients to the disease. The HLA-DR antigen appears to be triggered by many stimuli. After this inciting event, the synovial lining cells and subsynovial vessels proliferate, forming a pannus. Leukocytes invade, followed by a further inflammatory cascade involving proteases and cytokines. RF produces autoantibodies to IgG Fc fragment, influenced by HLA-DR polymorphism and associated with more severe, extra-articular disease. Again, RF is not specific to RA and can be detected in normal persons.

Diagnosis

Rheumatoid arthritis is a clinical diagnosis made by careful history and physical examination. Laboratory testing can be confirmatory but is also misleading if not interpreted in context. Radiographic evidence of erosions appears only several months to a year after disease onset. The American College of Rheumatology (ACR) published useful criteria in 1987 for the diagnosis of RA (Table 32-3). Symptoms must be present for at least 6 weeks for initial diagnosis.

Table 32-3 American College of Rheumatology Revised Criteria for Classification of Rheumatoid Arthritis (Traditional Format)

Criterion∗	Definition
1. Morning stiffness	Morning stiffness in and around the joints lasting at least 1 hour before maximal improvement.
2. Arthritis of three or more joint areas	At least three joint areas with simultaneous soft tissue swelling or fluid (not bony overgrowth alone) observed by physician. The 14 possible joint areas are right or left PIP, MCP, wrist, elbow, knee, ankle, and MTP joints.
3. Arthritis of hand joints	At least one joint area swollen as above in a wrist, MCP, or PIP joint.
4. Symmetric arthritis	Simultaneous involvement of the same joint areas on both sides of the body; bilateral involvement of PIP, MCP, or MTP joints is acceptable without absolute symmetry.
5. Rheumatoid nodules	Subcutaneous nodules over bony prominences or extensor surfaces or juxta-articular nodules regions, observed by physician.
6. Serum rheumatoid factor	Demonstration of abnormal amounts of serum rheumatoid factor by any method that has been positive in less than 5% of normal control subjects.
7. Radiologic changes	Radiologic changes typical of rheumatoid arthritis on posteroanterior hand and wrist radiographs, which must include erosions or unequivocal bony decalcification localized to, or most marked adjacent to, the involved joints (osteoarthritis changes alone do not qualify).

MCP, Metacarpophalangeal; MTP, metatarsophalangeal; PIP, proximal interphalangeal.

∗ Four or more criteria are needed for the diagnosis of rheumatoid arthritis (RA). Criteria 1 through 4 must be present for 6 weeks or longer. Presence of criteria is not conclusive evidence for the diagnosis of RA. Absence of criteria is not conclusively negative.

From Arnett FC. Revised criteria for the classification of rheumatoid arthritis. Bull Rheum Dis 1989;38:1. Used with permission.

Symmetric synovitis is the hallmark of RA and can be suggested by joint aspiration of synovial fluid, yielding over 2000 WBCs/mm³ without crystal, or by radiographic evidence of erosions. Because the cause of synovitis cannot be differentiated clinically, extra-articular manifestations can help distinguish RA from other inflammatory conditions.

History

Approximately 70% of patients with RA experience an insidious onset over weeks to months, 10% have an acute abrupt onset, and 20% have an intermediate onset, with increasing symptoms for days to weeks. Morning stiffness occurring for more than 1 hour is suggestive of RA. Morning stiffness results from joint immobilization during sleep and is not related to time of day. As opposed to patients with OA, patients with RA have constitutional symptoms such as fatigue, malaise, weight loss, low-grade fever, and anemia. Small joints in hands and feet (PIP, MCP) are typically involved first, with larger joints involved later. The joints themselves might be warm to the touch but are usually not erythematous. A pannus of inflamed synovium palpable as a rubbery mass of tissue strongly suggests RA.

The presentation of exacerbations of chronic rheumatoid synovitis might differ from those of early acute synovitis. Chronic inflammation causing fibrosis decreases synovial vascularity, reducing the amount of swelling from previous episodes. Although the frank swelling of burned-out RA appears less severe, the amount of pain, morning stiffness, constitutional symptoms (fatigue, malaise), and joint destruction on radiography shows this physical finding to be misleading. These episodes in patients with chronic, long-term RA should therefore not be considered improvement over more visible, earlier episodes of synovitis.

Less common presentations of RA include acute onset (which has the best prognosis) and palindromic RA, which is characterized by brief episodes of swelling of a large joint such as a knee, wrist, or ankle. Palindromic RA can therefore be easily misdiagnosed as gout.

Approximately 20% of patients with RA have intermittent symptoms. The remainders have progressive disease of varying severity. from slowly to rapidly progressive. In addition to morning stiffness, synovitis, and structural damage, RA exhibits classic manifestations in specific joints. Cervical spine involvement is common, whereas thoracic and lumbar spine involvement is rare. Early symptoms are neck stiffness and decreased motion, which can lead to neurologic complications from C1-C2 instability resulting from tenosynovitis of the transverse ligament of the first cervical vertebra (C1, which stabilizes odontoid process of C2), as well as disease of the apophyseal joints.

Neck pain without neurologic features tends to be self-limited and usually improves, but neck pain and neurologic symptoms often do not correlate well. A neurologic examination, even in the absence of neck pain, is therefore prudent in patients with RA. Radiographs of the cervical spine in flexion and extension might be needed to detect C1-C2 involvement, which necessitates caution during surgical procedures requiring intubation.

Physical Examination

Upper Extremity

Shoulder RA usually manifests as decreased ROM. Elbow RA is more accessible than shoulder RA for physical examination and joint aspiration. Elbow involvement can manifest with elbow pain and swelling; ulnar compression syndrome (paresthesia and weakness of fourth and fifth digits) can develop from the synovitis. The wrists are affected in most RA patients, in contrast to OA patients; carpal tunnel syndrome is seen frequently. RA usually involves the MCP and PIP joints rather than the DIP joints. Classic late changes such as swan neck and boutonnière deformities and ulnar deviation of the MCP joints caused by ligamentous laxity might occur. The swan neck deformity is characterized by flexion of the DIP and MCP joints and hyperextension of the PIP joint, probably resulting from shortening of the interosseous muscles and tendons and shortening of the dorsal tendon sheath. The boutonnière deformity results from avulsion of the extensor hood of the PIP because of chronic inflammation. This causes the PIP to pop up in flexion while the DIP stays in hyperextension.

Lower Extremity

Hip involvement in RA might be difficult to detect on physical examination and might manifest as only a small decrease in ROM. If pain develops, it can be felt in the buttock, lower back, groin, thigh, or medial aspect of the knee. RA of the knee is usually easily apparent on examination. A Baker’s cyst (posterior herniation of the joint capsule to the popliteal area) might occur and can be diagnosed by ultrasound. Rupture of a Baker’s cyst into the posterior leg might mimic thrombophlebitis. RA might involve the MTP, talonavicular, and ankle joints, causing gait problems. The tarsal tunnel containing the posterior tibial nerve can be compressed by synovitis, causing burning paresthesias on the sole of the foot made worse by weight bearing.

Joint Deformities

The synovitis of RA has many effects on cartilage, bone, muscles, tendons, and ligaments. Cartilage and bone erode, and muscles and tendons shorten in response to chronic inflammation. Ligaments are weakened by collagenases released by inflamed synovium and pannus. Upper extremity joints (shoulder, wrist, elbow) are prone to more severe deformities, as previously noted, than knees and ankles because splinting (avoiding joint motion to minimize pain) is easier in these lower extremity joints. The decreased use of these joints leads to more destruction by tendon shortening and contraction of the articular capsule.

Extra-Articular Manifestations

Systemic constitutional symptoms such as fatigue, malaise, anorexia, weight loss, and fever occur in addition to joint inflammation and destruction in RA. Significant inflammation of almost all organ systems occurs. Patients have an increased incidence of renal, cardiac, pulmonary, and neurologic disorders, serious infections, and hematologic malignancies such as non-Hodgkin’s lymphoma. Subcutaneous rheumatoid nodules occur frequently in RA patients, usually in areas subject to pressure such as the elbows and sacrum. Their onset can be abrupt or gradual, and they might also resolve spontaneously. Biopsies are sometimes required to differentiate these from a gouty tophus or xanthoma. Rheumatoid nodules can also occur throughout the body, including (rarely) organs such as the lungs and heart.

Pulmonary involvement can include pleural effusions, interstitial fibrosis, solitary or multiple nodular lung disease, and pleurisy. Asymptomatic pericarditis diagnosed by echocardiography during RA exacerbations is relatively common but rarely results in cardiac-related sequelae. Nodules can occur rarely in the myocardium, heart valves, and aorta. Renal and GI complications are generally secondary to the treatment of RA rather than arising from the disease itself. Eye dryness from keratoconjunctivitis sicca, episcleritis, or scleritis is associated with RA. Hematologic complications of RA include a hypochromic microcytic anemia with a low serum ferritin level and low or normal iron-binding capacity. Because many RA patients are taking NSAIDs, it can be difficult to distinguish anemia associated with their RA from NSAID-induced GI blood loss. Felty’s syndrome (RA, splenomegaly, leukopenia, leg ulcers, lymphadenopathy, thrombocytopenia, HLA-DR4 haplotype) is most common in patients with severe, nodule-forming RA.

Laboratory Studies

Arthritis panels should not be routinely performed and might only confuse the diagnosis. RF, ESR, uric acid level, ANA, and radiographic abnormalities all increase with age in the general population, even in the absence of disease. Therefore, laboratory studies should be reviewed as confirmatory of the clinical diagnosis made by careful history and physical examination.

Rheumatoid factor, ANA, and ESR are normally the most helpful tests to diagnose RA. RF is present in 80% to 90% of patients with RA. Therefore, 10% to 20% of patients with RA never have a positive RF. Also, up to 4% of normal young persons have low levels of RF. Moreover, RF titers are not helpful in following disease progression; when a patient is discovered to have a positive RF, repeating the test is of no value. Repeating an RF 6 to 12 months later for patients with initially negative RF may be useful when RA is still being strongly considered. RF can be increased in other diseases, mainly chronic infections (Lyme disease, subacute bacterial endocarditis, tuberculosis, syphilis), viral infections (infectious mononucleosis, cytomegalovirus, influenza), parasitic infections, and other chronic inflammatory diseases such as sarcoidosis, pulmonary interstitial disease, and noninfectious hepatitis.

Anti–cyclic citrullinated peptide (anti-CCP) antibody is another laboratory test useful in the diagnosis of RA when the diagnosis is in question or the RF is negative. Anti-CCP is more specific than rheumatoid factor for RA with 95% specificity and 69% sensitivity. Positive anti-CCP serology has also been linked with more severe radiologic progression of joint erosions from RA (Nishimura at el., 2007). Anti-CCP can also be positive in patients with active tuberculosis or other autoimmune diseases.

Other serum tests include ANA titers, complement, ESR, and CBC. Abnormal ANA titers indicate SLE, Sjögren’s syndrome, and scleroderma, but up to 30% of RA patients also have abnormal ANAs. Complements (CH50, C3, and C4) are decreased in SLE but are normal or increased in RA. The ESR, a nonspecific marker of inflammation, might help differentiate RA from other noninflammatory diseases. C-reactive protein (CRP), an acute-phase reactant, is also nonspecific but increases more rapidly than the ESR in early inflammation. A CBC showing a mild normochromic, normocytic anemia and a normal WBC count suggests RA. Thrombocytosis might also mimic disease activity as another acute-phase reactant, and eosinophilia might be seen.

Synovial fluid analysis in RA shows a yellow-white, turbid, but sterile fluid without crystals. WBC counts of synovial fluid in RA are typically 10,000 to 20,000 cells/mm³ but are at least higher than 2000/mm³, with more than 75% PMNs. Synovial CH50 is lower than serum levels, and the serum and synovial glucose difference is usually higher than 30 mg/dL.

Imaging Studies

Radiography is indicated early when infection or fracture must be ruled out, the patient has a history of malignancy, the physical examination fails to localize the source of pain, or pain persists despite conservative treatment. Early RA might show only soft tissue swelling. Advanced destruction on radiographs should not be required to initiate disease-modifying therapy if a diagnosis of RA is strongly suspected clinically. In late-stage disease, radiographs might show marginal bony erosions, periarticular osteoporosis, and joint space narrowing, especially in the hands and feet (Figs.32-8 and 32-9).

Figure 32-8 Rheumatoid arthritis marginal erosions and joint space narrowing.

(From Resnick D, Yu JS, Sartoris D. Imaging. In Kelley WN Harris ED, Ruddy S, et al [eds]. Textbook of Rheumatology, 5th ed, vol 1. Philadelphia, Saunders, 1997, pp 626-686.)

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