Hari P. Bezwada
Jess H. Lonner
Robert E. Booth Jr.
In the presence of arthritis, pain is the leading reason for patients to present for medical evaluation. They may have either monoarticular or polyarticular complaints. Osteoarthritis affects >40 million people annually, and there is an association with advanced age. Rheumatoid arthritis, although far less prevalent, commonly has a younger age of onset and often is more debilitating than osteoarthritis, with polyarticular and systemic manifestations. It is important to differentiate inflammatory from noninflammatory arthritis, as the diagnosis has clear implications in terms of both treatment and prognosis.
Osteoarthritis
Osteoarthritis is the end result of various disorders that lead to structural or functional failures in one or both knees. The knee is a diarthrodial joint with bone, cartilage, and connective tissue. The subchondral bone is covered by hyaline cartilage, which is made up of type II collagen, chondrocytes, and proteoglycans. The arrangement of type II collagen along the joint surface provides tensile strength. Proteoglycans assist with water retention and provide a low-friction bearing surface and shock absorption. Normal synovial fluid provides nourishment to hyaline cartilage and has viscoelastic properties. The volume of synovial fluid increases in osteoarthritis and is high in prostaglandins, collagenases, tumor necrosis factor 1, and interleukins. Osteoarthritic synovial fluid is also low in hyaluronate.
Repetitive microtrauma is thought to create biomechanical alterations in the cartilage matrix, which leads to subsequent breakdown of both cartilage and subchondral bone. The water content within the type II collagen increases and proteoglycan synthesis increases in an attempt to promote joint repair. Chondrocytes within the cartilage matrix eventually become overwhelmed with attempting repair and release metalloproteinases. The metalloproteinases cause further destruction and thinning of the cartilage matrix. More subchondral bone becomes exposed as the cartilage thins, leading to increased stresses and subchondral sclerosis along with the development of osteophytes. Subchondral cysts form as synovial fluid is forced beneath the joint surface.
The severity of osteoarthritis is best determined by reviewing weight-bearing radiographs. Typical radiographs include weight-bearing anteroposterior and lateral views. Patellar skyline or Merchant views are best to evaluate the patellofemoral joint, patellar tracking, and patellar tilt. A weight-bearing 45-degree flexion or notch view (posteroanterior) is useful in evaluating degenerative changes mostly involving the posterior femoral condyles. Magnetic resonance imaging, nuclear scans, and computed tomography have limited utility.
Inflammatory Arthritis
Classic signs of inflammatory arthritis include warmth, erythema, swelling, synovitis, and pain. The presentation may involve a single or multiple joints with additional systemic complaints. The illness may have a waxing and waning course. The level of joint involvement may be symmetrical or asymmetrical and acute or chronic. The keys to diagnosis include careful history and physical examination and judicious review of appropriate laboratory and imaging studies.
Rheumatoid arthritis (RA) is the most prevalent chronic, symmetrical inflammatory polyarticular arthritis. Clinical
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findings include rheumatoid nodules, symmetrical synovitis, seropositive rheumatoid factor, synovial fluid inflammatory findings, and radiographic changes including erosions and osteopenia. Osteophytes and sclerosis are unusual in RA.
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TABLE 18-1 Differential Diagnosis of Inflammatory Arthritis |
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Lyme disease may have either a monoarticular or polyarticular presentation, and there is typically a history of a tick bite and a target skin lesion (erythema chronicum migrans). However, both the history and presence of constitutional symptoms are variable. Serologies (Lyme titers) are useful in confirming the diagnosis; synovial fluid analysis may show an elevated white blood cell count with a preponderance of neutrophils.
Other inflammatory arthropathies include Reiter disease, psoriatic arthritis, and seronegative rheumatoid arthritis. Various rheumatologic tests, such as rheumatoid factor, antinuclear antibody, and HLA B-27, can help establish the diagnosis. Arthritis may also be associated with HIV infection, hepatitis C infection, inflammatory bowel disease, crystal deposition, and connective tissue disorders (Table 18-1).
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TABLE 18-2 Synovial Fluid Analysis |
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Synovial Analysis
Synovial fluid analysis is a useful adjunct in differentiating inflammatory, noninflammatory, and septic arthritis. Aspiration should be performed with caution in patients with overlying cellulitis or soft tissue infection because of the risk of direct inoculation of the joint. Normal knee synovial fluid has a volume of several milliliters and a white blood cell count <200. Synovial fluid also contains hyaluronate (glycosaminoglycan) produced by synoviocytes and is typically transparent with a straw color.
Abnormal synovial fluid has increased volume, decreased viscosity, diminished clarity, and a change in color. Microscopic analysis for the numbers and types of cells as well as the presence of crystals is important. Synovial fluid culture, serologic analysis, and immunologic evaluations should be performed as necessary (Table 18-2).
Treatment
Nonoperative Treatment
The first line of treatment for arthritis of the knee includes both physical modalities and pharmacologic interventions. The goals are simply to decrease pain and improve function. Presently, little can be done to reverse the degenerative process (Tables 18-3, 18-4).
Physical Therapy
Physical therapy can improve and maintain the patient's functional level. Physical therapy programs should consist of stretching, proprioceptive exercise, strengthening, and conditioning. Range of motion and stretching are critical parts of a therapy program as they help to maintain function. The quadriceps atrophy that occurs with knee arthritis may be both rapid and dramatic. Most exercise and strengthening programs are focused on the quadriceps mechanism, although hamstring strengthening may be important for balancing the quadriceps/hamstrings ratio. Patients with knee arthritis who undergo quadriceps strengthening show
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improvements in quadriceps strength, knee pain, and function. Isometric exercises are generally best tolerated. General aerobic conditioning from low-impact exercises improves both patients' overall health and arthritic symptoms. Water therapy is especially useful in obese patients as the force of gravity is virtually eliminated. Warm water hydrotherapy raises body temperature, causes superficial vasodilatation, increases peripheral circulation, has a sedative effect on nerve endings, and causes muscle relaxation.
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TABLE 18-3 Medical Treatment of Inflammatory Arthritis |
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Biomechanical Devices
Valgus-producing unloader knee braces may be helpful in varus gonarthrosis especially when there is instability and lateral thrust. These braces use a three-point pressure system to decrease the deformity and off-load the affected compartment. Brace-wear compliance is variable, as unloader braces tend to be uncomfortable and less effective in the obese. Orthotics, namely lateral heel wedges, may also be helpful in varus gonarthrosis. Patients with valgus knee deformities in association with a planovalgus foot may benefit from a foot-ankle orthosis. Assistive devices such as a cane or walker substantially reduce forces across the affected joint.
External Energy
Therapeutic heat may produce analgesia of the free nerve endings and subsequent muscle relaxation. The obligatory increase in blood flow from local heat may also wash out inflammatory mediators. Ultrasound is a deep heat modality that may have efficacy in relieving arthritis pain. It also has mechanical effects that create fluid movements around cells, which in turn alters cell permeability, promotes collagen synthesis, and alters painful nerve fibers. The use of transcutaneous electrical neuromuscular stimulation (TENS) has been controversial. Cryotherapy may reduce pain by reducing muscle spindle activity and raising the pain threshold.
Weight Loss and Activity Modification
Modest weight loss may have dramatic effects on arthritis pain. Joint reactive forces may reach three to four times body weight across the knee. This factor increases to sevenfold to eightfold across the patellofemoral joint in deep flexion. The increased joint forces from body weight are also affected by cyclical loading, i.e., number of steps taken. Activity modification also may be chondroprotective. Excessive impact loading of the knee should be avoided as it may have a deleterious effect on knee function and arthritis.
Pharmacologic Interventions
The most commonly used nonnarcotic analgesic is acetaminophen, which can be effective, particularly in milder cases, when used frequently as a first-line treatment for arthritis. The risks include hepatotoxicity and interstitial nephritis in large regular doses. Narcotic analgesics may be effective for temporary pain relief, but have well-known side effects on the central nervous system and gastrointestinal system.
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TABLE 18-4 Treatment of the Arthritic Knee |
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Nonsteroidal Anti-inflammatory Drugs (NSAIDs).
One of the first-line therapies in the medical management of inflammatory arthritis is nonsteroidal anti-inflammatory drugs (NSAIDs). Salicylates were among the first NSAIDs used with typical doses of 300 to 600 mg three to four times a day. Salicylates should not be used in gout as they have been implicated in increasing serum uric acid levels. The main side effects are gastrointestinal, hematologic, hepatic, and renal.
Most NSAIDs inhibit the cyclo-oxygenase enzymes. The exceptions include nonacetylated salicylates such as Arthropan, Trilisate, and Disalcid. Cyclo-oxygenase is critical in producing prostaglandins. Prostaglandins have many effects in the body, including vasodilation, gastrointestinal mucosal protection, and inflammation. Prostaglandin E2 may contribute to local inflammation within the joint space. It appears that reducing the amount of prostaglandin E2 leads to less joint pain. The most common side effects of NSAIDs are on the gastrointestinal system; the frequency ranges from 15% to 35%. Renal toxicity also may occur as a result of interstitial nephritis or renal hypoperfusion.
Two subgroups of cyclo-oxygenase have been discovered. Cyclo-oxygenase-1 (COX-1) is found in most tissues and is important in maintaining mucosal integrity of the gastrointestinal tract and renal perfusion. Cyclooxygenase-2 (COX-2) is found mostly at the site of inflammation. Selective COX-2 inhibitors are associated with improved gastric tolerance compared with other NSAIDs. Recent evidence has suggested that there is an increase in adverse cardiac events in patients with cardiac disease treated with some COX-2 inhibitors, so the indication for their use over an extended period of time is yet to be defined.
Disease-modifying antirheumatic drugs include gold compounds, antimalarials, sulfasalazine, penicillamine, cytotoxic drugs (azathioprine, methotrexate), cyclosporine, and flunomide. Recent developments include tumor necrosis factor antagonists, examples of which include etanercept, infliximab, and adalimumab (Table 18-3).
Injectable Corticosteroids.
Typical intra-articular injection combines a synthetic corticosteroid and local anesthetic. The addition of a local anesthetic reduces the incidence of postinjection symptom flare. Multiple studies have supported an improvement in symptoms over placebo 1 to 2 weeks following injection. Yet by 4 weeks, the results become very similar. Although corticosteroids are commonly administered, there is little literature to direct surgeons as to the optimal steroid preparation, dosage, frequency, and length of treatment. Systemic side effects from corticosteroid injections include allergic reactions, intra-articular infection, and potential hyperglycemia in brittle diabetics. Frequent injections over the long term are associated with local fat atrophy and cartilage degeneration from decreased collagen formation. Additionally, pain masking may lead to overuse and cartilage breakdown. Therefore most clinicians recommend that injections be given no more frequently than every 3 or 4 months.
Viscosupplementation.
Hyaluronic acid is a key constituent of both cartilage and synovial fluid. Osteoarthritis is associated with a loss of hyaluronic acid from the cartilage and the production of low-molecular-weight hyaluronic acid by synoviocytes. The result is the presence of a less viscous hyaluronate in the arthritic joint. Hyaluronic acid injection may be considered for patients with symptomatic osteoarthritis that has not responded to other conservative measures.
Several products are available; the differences between them are mainly based on the molecular weight of the cross-linked hyaluronic acids. It is not clear how formulation differences impact clinical efficacy or response. Multiple studies appear to support the efficacy of each of these formulations, with a low-risk side effect profile. The most common side effect is a sterile partial inflammatory effusion, which can be difficult to distinguish from infection. Hyaluronic acid appears better than placebo, and the effect is similar to that of nonsteroidal anti-inflammatories. The analgesic effect appears to last for several months. A course of viscosupplementation may be repeated every 6 months, although the efficacy may be reduced and the risk of allergic reaction may increase.
Nutraceuticals/Dietary Supplements
Although studies are scant and poorly controlled, there has been some suggestion that certain naturally occurring dietary supplements, herbal remedies, and so-called nutraceuticals may be helpful in the management of knee arthritis. Omega-3 fatty acids may reduce the production of inflammatory mediators in the body and have been shown to reduce stiffness in patients with rheumatoid arthritis. Methylsulfonylmethane (MSM), glucosamine, and chondroitin sulphate are popular supplements that have been touted for their virtues in slowing down the progression of arthritis. Glucosamine ostensibly enhances cartilage production and reduces pain to a level similar to that of NSAIDS, although conflicting reports have suggested this to be a placebo effect. Chondroitin sulfate may inhibit proteases and thereby slow the progression of arthritis and reduce inflammation. Antioxidants, namely vitamins C, D, E, may be beneficial in cartilage formation, but further study is necessary.
Topical Agents
Aspercreme (10% trolamine salicylate cream) is absorbed percutaneously and hydrolyzed into salicylic acid. Topical application of capsaicin affects the A, delta, and C nerve fibers and secondarily leads to depletion of substance P.
Surgical Management
Arthroscopy
Arthroscopy has a limited role in the management of the osteoarthritic knee. The presence of mechanical symptoms is the main indication for arthroscopic intervention in the presence of degenerative joint disease (DJD), usually when arthritis is mild and associated with a meniscus tear. Severe or end-stage arthritis should be excluded with weight-bearing radiographs prior to arthroscopy as the likelihood of success is dependent on the degree of arthritic changes. Arthroscopic debridement in osteoarthritis has not been better than placebo. An additional role of arthroscopy may be in the case of isolated cartilage lesions or defects in which
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microfracture, subchondral drilling, or abrasion techniques can be used. The clinical data to support these techniques remain limited. Mosaicplasty or autologous chondrocyte transplantation can be performed in young patients with small lesions but are not presently advocated for more diffuse and advanced degenerative disease. Arthroscopic synovectomy with or without biopsy may have a role in inflammatory synovitis.
Osteotomy
Valgus-producing high tibial osteotomy is indicated in patients with varus gonarthrosis and isolated medial compartment arthritis. Varus-producing distal femoral osteotomy is indicated in patients with valgus gonarthrosis and isolated lateral compartment arthritis. Other general requirements include age younger than 50 years, intact anterior cruciate ligament, minimal flexion contracture, good motion, noninflammatory arthritis, and no dynamic thrust. Because of the apparent short-term superiority of unicompartmental arthroplasty, periarticular osteotomies are not being performed as frequently as a decade ago, except perhaps in young laborers with unicompartmental disease.
Unicompartmental Arthroplasty
The role of unicompartmental arthroplasty in the arthritic patient continues to evolve. Minimally invasive techniques are enhancing the popularity of this procedure, particularly as an alternative to periarticular osteotomy. In the past, the ideal patient was older than 60 years of age and led a sedentary lifestyle. More current indications might include active middle-aged patients undergoing a first arthroplasty as a staged procedure before total knee arthroplasty (TKA). Benefits might include less invasive surgery, less blood loss, more natural knee kinematics (retaining both cruciate ligaments), a faster recovery than with TKA, and more pronounced pain relief than osteotomy. Isolated monocompartmental arthritis of the tibiofemoral joint or patellofemoral joint remain true indications for unicompartmental arthroplasty. Degenerative changes in other compartments and inflammatory arthritis are contraindications.
Total Knee Arthroplasty
Total knee arthroplasty is the procedure of choice for most patients with severe tricompartmental arthritis and provides reliable and durable results. Inflammatory arthritis, deformity, contractures, and instability are best managed with total knee arthroplasty rather than the other surgical procedures.
Suggested Readings
Argensen JN, Chevrol-Benkeddache Y, Aubaniac JM. Modern unicompartmental knee arthroplasty with cement: a three to ten year follow-up. J Bone Joint Surg Am. 2002; 84:2235-2239.
Behrens F, Shepard N, Mitchell N. Metabolic recovery of articular cartilage after intra-articular injections of glucocorticoid. J Bone Joint Surg Am. 1976; 58:1157-1160.
Bradley JD, Brandt KD, Katz BP, et al. Comparison of an anti-inflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med. 1991; 325:87-91.
Buckwalter JA, Mankin HA. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect. 1998; 47:487-504.
Dervin GF, Stiell IG, Rody K, et al. Effect of arthroscopic debridement for osteoarthritis of the knee on health-related quality of life. J Bone Joint Surg Am. 2003; 85:10-19.
Ethgen O, Bruyere O, Richy F, et al. Health-related quality of life in total hip and total knee arthroplasty. A qualitative and systematic review of the literature. J Bone Joint Surg Am. 2004; 86:963-974.
Felson DT, Zhang Y, Anthony JM, et al. Weight loss reduces the risk for symptomatic knee osteoarthritis in women. The Framingham Study. Ann Intern Med. 1992; 116:535-539.
Goldenberg DL, Reed JI. Bacterial arthritis. N Engl J Med. 1985; 312: 764-771.
Hanssen AD, Stuart MJ, Scott RD, et al. Surgical options for middle-aged patients with osteoarthritis of the knee joint. Instr Course Lect. 2001; 50:499-511.
Holden DL, James SL, Larson RL, et al. Proximal tibial osteotomy in patients who are fifty years old or less. A long-term follow-up study.J Bone Joint Surg Am. 1988; 70:977-982.
Leopold SS, Redd BB, Warme WJ, et al. Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee. A prospective, randomized trial. J Bone Joint Surg Am. 2003; 85:1197-1203.
McAlindon TE, LaValley MP, Gulin JP, et al. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000; 283:1469-1475.
Moseley JB, O'Malley K, Petersen NJ, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002; 347:81-88.
Nussmeier NA, Whelton AA, Brown MT, et al. Complications of COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005; 352:1081-1091.
Soll AH. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med. 1991; 114:307.